* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Russian Journal of General Chemistry, 2005, vol. 75, # 5, p. 782 - 789
3
[ 121-89-1 ]
[ 5000-65-7 ]
Reference：
[1] Patent: CN106242957, 2016, A,
4
[ 121-89-1 ]
[ 2227-64-7 ]
Yield
Reaction Conditions
Operation in experiment
97%
With aluminum (III) chloride; bromine In diethyl ether at 0 - 20℃; for 1 h;
2-bromo-1-(3-nitrophenyl)ethanone (2a-1). To a suspension of commercially available 3- nitroacetophenone (4.82 g, 29.19 mmol) in anhydrous diethyl ether (25 mL) was added aluminum chloride (0.16 g, 1.20 mmol). The reaction mixture was then cooled to 0°C before dropwise addition of bromine (1.50 mL, 29.19 mmol). The reaction was stirred for lh at room temperature until complete conversion of the starting material (1H NMR monitoring) and quenched quickly to avoid di-brominated compound formation. After addition of water (30 mL), the mixture was extracted with diethyl ether (3 x 30 mL) and dried with MgSO4 to afford compound 2a-1 as a yellowish brown solid (5.73 g, 97percent yield). 1H NMR (CDCl3, 200 MHz): δ 4.50 (s, 2H, H1), 7.73 (t, J = 8.0 Hz, 1H and H7), 8.31 (ddd, J = 7.8, 1.7, 1.1 Hz, 1H, H8), 8.43 (ddd, J = 8.2, 2.3, 1.1 Hz, 1H, H6), 8.76 (t, J = 1.9 Hz, 1H, H4). 13C NMR (CDCl3, 200 MHz): δ 30.4, 123.9, 128.2, 130.4, 134.6, 135.2, 148.6, 189.5. MS-ESI (m/z): [M+H]+= 244.9.
97%
With aluminum (III) chloride; bromine In diethyl ether at 0 - 20℃; for 1 h;
To a suspension of commercially available 3-nitroacetophenone (4.82 g, 29.19 mmol) in anhydrous diethyl ether (25 mL) was added aluminum chloride (0.16 g, 1.20 mmol). The reaction mixture was then cooled to 0°C before dropwise addition of bromine (1.50 mL, 29.19 mmol). The reaction was stirred for 1h at room temperature until complete conversion of the starting material (1H NMR monitoring) and quenched quickly to avoid di-brominated compound formation. After addition of water (30 mL), the mixture was extracted with diethyl ether (3 x 30 mL) and dried with MgSO4 to afford compound 2 as a yellowish brown solid (5.73 g, 97percent yield). 1H NMR (CDCl3, 200 MHz): δ 4.50 (s, 2H, H1), 7.73 (t, J = 8.0 Hz, 1H and H7), 8.31 (ddd, J = 7.8, 1.7, 1.1 Hz, 1H, H8), 8.43 (ddd, J = 8.2, 2.3, 1.1 Hz, 1H, H6), 8.76 (t, J = 1.9 Hz, 1H, H4). 13C NMR (CDCl3, 200 MHz): δ 30.4, 123.9, 128.2, 130.4, 134.6, 135.2, 148.6, 189.5. MS-ESI (m/z): [M+H]+= 244.9.
91%
With N-Bromosuccinimide; tetrachlorosilane In acetonitrile at 20℃; for 7 h;
General procedure: To a mixture of NXS and substrate (1 or 6) in CH3CN at room temperature was added SiCl4 and the mixture left to stir until TLC showed the disappearance of the starting material. The reaction was then poured onto H2O and the mixture extracted with CH2Cl2. The extracts were combined, dried over MgSO4 and evaporated. The residue was purified by recrystallization (pet. ether-Et2O, 3:1) to give pure 2b-2g, 3b, or by silica gel column chromatography (hexane-EtOAc 10:1 or 30:1) to give pure 2a,h,i, 3a-5 or 7-9, respectively
84%
at 20℃; for 1 h; Inert atmosphere
Synthesis 53; 2-Bromo-1-(3-nitrophenyl)ethanone/77-Nitroacetophenone (20 g) was dissolved in acetic acid (150 mL) under argon. Pyridinium tribromide (38.7 g) was added at once; the reaction was allowed to stir at room temperature for 1 hour and then quenched with water (250 mL). The product was filtered and air dried to give the title compound (25 g, 84percent).
78%
With hydrogen bromide; potassium iodide; sodium nitrite In water; acetonitrile at 0 - 20℃; for 12 h;
General procedure: In a RBF cooled in ice bath at 0 C, HBr(12 mmol, in 2 ml of water) was taken. To this a solution of NaNO2(5 mmol, in 5ml of water) was added drop wise. The reaction was stirred for 15min maintaining the temperature at 0 °C and KI (5 mol percent) was added. After 10 min ketone(10 mmol) was added at once. After 15 min reaction temperature was brought to room temperature slowly. Reaction was monitored by TLC (ethyl acetate: pet ether, 1:9). After completion of reaction 50 ml of CHCl3 was added and organic layer separated. Aqueous layer was extracted with 25 ml of CHCl3 and combined organic layer was washed with 10percent NaHSO3 solution (2 x 20 ml) and 10percent NaHCO3 solution (2 x 20 ml).The organic layer was dried over sodium sulphate and concentrated under reduced pressure. Pure product was obtained after column chromatography (silica gel, 60-120, eluentethyl acetate: pet ether).
73%
With bromine In acetic acid at 55℃; for 0.5 h;
48mmol of m-nitroacetophenone was dissolved in 300mL of glacial acetic acid and warmed to 55°C. 48mmol of bromine was then added drop-to-drop allowing the discoloration of the solution before add next drop. After 30min at 55°C, 101g of crushed ice was added to the reaction and the formed precipitated filtered out, washed with water and recrystallized from ethanol/petroleum ether, rendering the compound 2-brome-1-(m-nitrophenyl)ethan-1-one. Yield: 73percent.
70%
With phenyltrimethylammonium tribromide In tetrahydrofuran at 20℃; for 1 h;
A solution of phenyltrimethylammonium tribromide (50.1 g, 133 mmol) in THF (200 mL)was added dropwise to a stirred solution of 1-(3-nitrophenyl)ethanone (20 g, 121 mmol)in THF (200 mL) at room temperature. The reaction mixture was allowed to stir at roomtemperature for lh. The white suspension was filtered and the filter cake was washed withTHF, the filtrate was evaporated in vacuum to give a yellow oil. The residue was then dissolved in EtOAc and was washed with water. The organic layer was dried (MgSO4) and evaporated in vacuum to give a yellow oil that solidified into an yelLow solid. Solid recrystallised from propan-2-ol and final product was isolated as an off-white solid. 2-Bromo-l-(3-nitrophenyl)ethanone (20.5 g, 70 percent yield).(‘H, 600 MHz, 20°C, CDC13) 8: 8,83 (IH, t, 3 = 2Hz), 8.49 (IH, ddd, I = 1.0, 2.3, 8.2Hz), 8.34 (1H, ddd, I = 1.0, 1.7, 7.8 Hz), 7.75 (1H, t, J = 8.1 Hz), 4.49 (2H, s).(‘3C, 150 MHz, 20°C, CDC13) 8: 189.3, 148.5, 135.1, 134.4, 130.2, 128.1, 123.8, 29.9Melting point (mp): 90-9 1 DC.
70%
With phenyltrimethylammonium tribromide In tetrahydrofuran at 20 - 25℃; for 1 h;
A solution of phenyltrimethylammonium tribromide (50.1 g, 133 mmol) in THF (200 mL) was added dropwise to a stirred solution of l-(3-nitrophenyl)ethanone (20 g, 121 mmol) in THF (200 mL) at room temperature. The reaction mixture was allowed to stir at room temperature for lh. The white suspension was filtered and the filter cake was washed with THF, the filtrate was evaporated in vacuum to give a yellow oil. The residue was then dissolved in EtOAc and was washed with water. The organic layer was dried (MgS04) and evaporated in vacuum to give a yellow oil that solidified into a yellow solid. Solid recrystallised from isopropandl and final product was isolated as an off-white solid. 2-Bromo-l-(3-nitrophenyl)ethanone (20.5 g, 70 percent yield). (1H, 600 MHz, 20°C, CDC13) δΗ: 8.83 (1H, t, J = 2Hz), 8.49 (1H, ddd, J = 1.0, 2.3, 8.2 Hz), 8.34 (1H, ddd, J = 1.0, 1.7, 7.8 Hz), 7.75 (1H, t, J = 8.1 Hz), 4.49 (2H, s). (13C, 150 MHz, 20°C, CDC13) 6C: 189.3, 148.5, 135.1, 134.4, 130.2, 128.1, 123.8, 29.9. Melting point (mp): 90-91 °C.
34%
With bromine In acetic acid at 60℃; for 2 h;
Into a 500-mL 3-necked round-bottom flask, was placed a solution of l-(3-mtrophenyl)ethanone (50 g, 303 03 mmol, 1 00 eqmv) in acetic acid (300 mL), Br2 (53 5 g, 331 6 mmol, 1 00 equiv) The resulting solution was stirred for 2 h at 6O0C in an oil bath The reaction was then quenched by the addition of ice and the solids were collected by filtration The crude product was re-crystallized from ethyl acetate/petroleum ether in the ratio of 1 10 This resulted in 25 g (34percent) of 2-bromo-l-(3-mtrophenyl)ethanone as a white solid.
Reference：
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[2] Patent: WO2017/17004, 2017, A1, . Location in patent: Page/Page column 17
[3] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 10, p. 2192 - 2196
[4] Tetrahedron Letters, 2011, vol. 52, # 31, p. 4026 - 4029
[5] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2009, vol. 48, # 10, p. 1424 - 1430
[6] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 1, p. 184 - 187
[7] Patent: WO2010/32010, 2010, A1, . Location in patent: Page/Page column 101-102
[8] MedChemComm, 2017, vol. 8, # 12, p. 2258 - 2262
[9] European Journal of Inorganic Chemistry, 2013, # 36, p. 6156 - 6163
[10] Tetrahedron Letters, 2003, vol. 44, # 3, p. 439 - 442
[11] Synthetic Communications, 2003, vol. 33, # 11, p. 1917 - 1922
[12] Tetrahedron Letters, 2016, vol. 57, # 44, p. 4918 - 4921
[13] European Journal of Medicinal Chemistry, 2013, vol. 67, p. 142 - 151
[14] Journal of Medicinal Chemistry, 2013, vol. 56, # 10, p. 3833 - 3851
[15] Bulletin of the Chemical Society of Japan, 1987, vol. 60, # 3, p. 1159 - 1160
[16] Journal of Organic Chemistry, 2013, vol. 78, # 14, p. 7312 - 7317
[17] Patent: WO2014/17936, 2014, A2, . Location in patent: Paragraph 14
[18] RSC Advances, 2014, vol. 4, # 99, p. 56489 - 56501
[19] Patent: WO2015/112036, 2015, A2, . Location in patent: Page/Page column 26; 27
[20] Patent: WO2015/112036, 2015, A3, . Location in patent: Page/Page column 26; 27
[21] Journal of Medicinal Chemistry, 1992, vol. 35, # 16, p. 3045 - 3049
[22] RSC Advances, 2014, vol. 4, # 107, p. 62308 - 62320
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[24] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1986, vol. 25, p. 228 - 229
[25] European Journal of Organic Chemistry, 2013, # 8, p. 1551 - 1557
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[37] Patent: WO2009/90548, 2009, A2, . Location in patent: Page/Page column 29
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[39] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5589 - 5593
[40] Bulletin of the Korean Chemical Society, 2012, vol. 33, # 1, p. 111 - 114
[41] Journal of Heterocyclic Chemistry, 2012, vol. 49, # 4, p. 959 - 964
[42] Journal of Photochemistry and Photobiology B: Biology, 2012, vol. 115, p. 25 - 34
[43] Synlett, 2012, vol. 23, # 18, p. 2609 - 2614,6
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[45] Tetrahedron, 2013, vol. 69, # 31, p. 6392 - 6398
[46] Patent: WO2014/72486, 2014, A1, . Location in patent: Page/Page column 18-19
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[49] Heterocycles, 2015, vol. 91, # 11, p. 2113 - 2125
[50] RSC Advances, 2016, vol. 6, # 33, p. 27885 - 27895
[51] Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 8, p. 1166 - 1173
[52] Journal of Chemical Research, 2016, vol. 40, # 9, p. 545 - 548
[53] European Journal of Medicinal Chemistry, 2017, vol. 125, p. 1213 - 1224
[54] Journal of Medicinal Chemistry, 2017, vol. 60, # 4, p. 1591 - 1597
[55] Journal of the Chinese Chemical Society, 2017, vol. 64, # 12, p. 1408 - 1416
[56] Advanced Synthesis and Catalysis, 2018, vol. 360, # 8, p. 1628 - 1633
[57] European Journal of Organic Chemistry, 2018, vol. 2018, # 26, p. 3432 - 3436
5
[ 121-89-1 ]
[ 13651-07-5 ]
[ 2227-64-7 ]
Yield
Reaction Conditions
Operation in experiment
42%
With N-Bromosuccinimide; silica gel In methanol for 0.283333 h; Reflux
General procedure: The α-bromination reaction was carried out using acetophenone (1200 mg, 10 mmol), N-bromosuccinimide (2136 mg, 12 mmol), 10percent (w/w) silica gel (120mg) in 10 mL of methanol at reflux conditions until the disappearance of the substrate. (Note: 2136mg of N-bromosuccinimide was added portion wise i.e. 356 mg for each time in six portions). The progress of the reaction was monitored by TLC. The reaction mass was filtered after the completion of the reaction as per TLC and the catalyst was collected for reuse. The filtrate was concentrated under vacuum. Double distilled water was added to the reaction mixture and quenched with aqueous sodium thiosulfate and the product extracted with dichloromethane (Caution: Severe burning sensation of eyes was observed during the work-up process). The layers were separated and the organic layer was collected and washed thrice with distilled water (3×50mL). The collected organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The obtained crude product was purified by column chromatography over silica gel (60–120 mesh) using n-hexane–EtOAc (99:1 ratio). With the aim of studying the recycling of the catalyst, the isolated catalyst was washed with ethyl acetate (5mL) after its filtration from the reaction medium, collected and dried in vacuum at 70°C to a constant weight. Subsequently it was reused for the α-bromination of acetophenone and achieved 95percent, 86percent and 83percent yields of product (2a) for first, second and third reuse of catalyst respectively. All products gave spectroscopic data in agreement with the literature [15,21,27–30]. The method is also very practical for scale up in process development. We attempted large scale (100 gram scale) synthesis of 2-bromo-1-phenylethanone 2a and obtained fruitful results with isolated yields ranging from 93percent to 96percent.
Reference：
[1] Chinese Chemical Letters, 2014, vol. 25, # 1, p. 179 - 182
[2] Patent: WO2015/112036, 2015, A2, . Location in patent: Page/Page column 35; 36
[3] Patent: WO2015/112036, 2015, A3, . Location in patent: Page/Page column 35; 36
6
[ 67-56-1 ]
[ 121-89-1 ]
[ 2227-64-7 ]
Yield
Reaction Conditions
Operation in experiment
46%
for 3 h; Reflux
General procedure: Oxone (1.352 g, 2.2 mmol) was added to the well stirred solution of substrate (2 mmol) and NH4Br (0.215 g, 2.2 mmol) in methanol (10 ml) and the reaction mixture was allowed to stir at room temperature (or reflux temperature). After completion of the reaction, as monitored by TLC, the reaction mixture was quenched with aqueous sodium thiosulfate, and extracted with ethyl acetate (3.x.25 ml). Finally, the combined organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and removal of solvent in vacuo yielded a crude residue, which was further purified by column chromatography over silica gel (finer than 200 mesh) to afford pure products. All the products were identified on the basis of 1H NMR and mass spectral data.
14%
at 20℃; for 48 h;
General procedure: Oxone (1.352 g, 2.2 mmol) was added to the well stirred solution of substrate (2 mmol) and NH4Br (0.215 g, 2.2 mmol) in methanol (10 ml) and the reaction mixture was allowed to stir at room temperature (or reflux temperature). After completion of the reaction, as monitored by TLC, the reaction mixture was quenched with aqueous sodium thiosulfate, and extracted with ethyl acetate (3.x.25 ml). Finally, the combined organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and removal of solvent in vacuo yielded a crude residue, which was further purified by column chromatography over silica gel (finer than 200 mesh) to afford pure products. All the products were identified on the basis of 1H NMR and mass spectral data.
With silver trifluoromethanesulfonate In water; acetic acid at 110℃; for 6 h; Schlenk technique
General procedure: To a 25mL Schlenk tube, AuSBA-15 (6wtpercent, 20mg), AgOTf (0.05mmol) was added to a solution of phenylacetylene (1.0mmol) in HOAc/H2O (3.0mL, 15:1) under ambient air, the resulting mixture was stirred for 6hat 110°C. It was monitored by TLC. After the reaction was completed, the solvent was removed under reduced pressure and purified of the crude product by column chromatography on silica-gel afforded the desired compound.
83%
With Perfluorooctanesulfonic acid; C8AgF17O3S*H2O In water at 100℃; for 8 h; Darkness
General procedure: To the mixture of phenylacetylene (1 mmol), water (3.0 mL),silver perfluorooctanesulfonate (5 molpercent) and perfluorooctane sulfonateacid (2 molpercent) was added. The mixture was stirred at 100 Cfor 8 h. The solution was extracted with n-hexane (diethyl ether)(3 5 mL), the combined extract was dried with anhydrous MgSO4. The rest of the solution was used for the next cycle of reaction. Theextraction solvent was removed and the crude product was separatedby column chromatography to give the pure sample.
Reference：
[1] Chemical Communications, 2017, vol. 53, # 51, p. 6926 - 6929
[2] Journal of Organometallic Chemistry, 2017, vol. 851, p. 46 - 51
[3] Journal of Organometallic Chemistry, 2015, vol. 799-800, p. 122 - 127
[4] Chemische Berichte, 1913, vol. 46, p. 3733
[5] Organometallics, 2013, vol. 32, # 9, p. 2814 - 2826
8
[ 586-39-0 ]
[ 121-89-1 ]
Reference：
[1] Journal of the American Chemical Society, 2005, vol. 127, # 9, p. 2796 - 2797
[2] Angewandte Chemie, 1959, vol. 71, p. 626
[3] Journal of the American Chemical Society, 2009, vol. 131, p. 6076 - 6077
[4] Green Chemistry, 2015, vol. 17, # 5, p. 2750 - 2757
[5] Journal of the American Chemical Society, 2017, vol. 139, # 36, p. 12495 - 12503
[6] European Journal of Inorganic Chemistry, 2017, vol. 2017, # 47, p. 5604 - 5608
9
[ 7369-50-8 ]
[ 121-89-1 ]
Yield
Reaction Conditions
Operation in experiment
85.85%
at 140 - 165℃; for 20 h;
The 3000Kg-nitro ethylbenzene, 150g cobalt stearate into the oxidation reactor, was evacuated and replaced with oxygen, to the oxidation reactor through the oxygen control oxygen pressure 0.8Mpa, open stirred reactor, open the oxidation reactor steam the reaction was terminated heating, when the oxidation reaction Tanei Da to 165 , after the reaction started off steam, exhaust steam, open the cooling water, a slow cooling to 140 , 140 thermal control for 18 hours, when the amount of ketone containing up to 80percent when with the kettle and pressure oil to oxidation reaction to acid tank, acid tank to start stirring slowly added 30percent sodium hydroxide solution 100Kg, adjusted PH to 7, then add a saturated solution of sodium carbonate 30Kg, adjusted PH to 8.5, stirred for 30 minutes, allowed to stand for 1.5 hours to stop stirring, layered sodium nitrobenzene solution put to the reservoir, between nitrobenzoic acid to be recovered, the oxidation reaction of oil to the crystallization reactor, cooling to freeze 10 , centrifugal rejection filter , washing, drying in 2350kg (Melting point 78.5 ), distilled liquor recovered 495kg (including the amount of 19.16percent ketone, and then for the oxidation), inter-nitroacetophenone product yield 85.85percent.
60%
With copper; Selectfluor In water; acetonitrile at 20℃; for 4 h;
m-Nitroethylbenzene 0.2 mmol,Copper powder 0.02 mmolAnd Selectfluor 0.02mmol in turn into a 10mL pressure sealed container,Add 2 mL of a mixture of acetonitrile and water (CH3CN/H2O = 400:1).The mixture was stirred at room temperature and the reaction was monitored by TLC. The reaction was completed after 4 hours.The reaction solution was diluted with dichloromethane 10 mL,Filtered to obtain a clear solution, after distillation of the solvent, column chromatography(eluent ratio: petroleum ether to ethyl acetate volume ratio 20:1) separation,The washings were collected and the solvent was evaporated to give m-nitroacetophenone in a yield of 60percent.
Reference：
[1] Patent: CN105461565, 2016, A, . Location in patent: Paragraph 0045; 0046
[2] Patent: CN105085205, 2018, B, . Location in patent: Paragraph 0077; 0078; 0079
[3] Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation), 1959, vol. 32, p. 1806,1810; engl. Ausg. S. 1845, 1848
10
[ 98-86-2 ]
[ 121-89-1 ]
Yield
Reaction Conditions
Operation in experiment
90.3%
at -10℃; for 0.166667 h;
400 ml of concentrated sulfuric acid was added to a 1000 ml reaction flask, 180.0 g (1.5 mol) of acetophenone was added dropwise,120ml concentrated sulfuric acid and 80ml fuming nitric acid mixed into the system,The entire process control system temperature does not exceed -10 , after dripping continue to react for 10min,TLC detection reaction ends. Stirring the state slowly into the system into a large number of ice water,The filter cake is washed with saturated sodium carbonate to give the crude product.The crude product was recrystallized from ethanol to give 223.5 g of pale yellow needle-like crystals,Yield 90.3percent, content ≥ 99percent.
82.1%
at -10 - -5℃; for 0.333333 h;
At -10 to -5 ° C,To the reactor was added 300g mass fraction of 98percent concentrated sulfuric acid,Dropwise add 120g (1mol) of acetophenone,A nitrating agent (228 g of concentrated sulfuric acid mixed with 171 g of fuming nitric acid) was slowly added dropwise to the reactor,And keep the reaction temperature below -10 ° C,The addition was complete and stirred for 20min to complete the reaction,The reaction mixture was poured into 1000 g of crushed ice with vigorous stirring,A large number of solid precipitation,Suction filtration,Ice water washing,dry,Obtained yellow crystal powder 3-nitro-acetophenone 135.5g,The yield was 82.1percentThe test has a melting point of 76-78 ;
78%
at -5℃;
At low temperature (ice bath), acetophenone (17.6g, 0.146mol) was added concentrated sulfuric acid (90ml), and cooled to -5 deg.] C, was slowly added dropwise a precooled solution of a mixed acid solution (15ml of concentrated nitric acid, concentrated sulfuric acid 18ml), to control the reaction at a low temperature.After the reaction mixture, the reaction solution was put into 500g of crushed ice, melted filtration, cold water and the resulting solids were washed with ethanol, filtering, adding ethanol and water (volume ratio 10: 1) and recrystallized after crystallization The crude product was filtered to give 3-nitrophenyl ethanone (III) (18.8g, 78percent yield).
55%
at -5 - 5℃; for 0.25 h;
8mL of acetophenone was added over 20mL of concentrated sulfuric acid (d=1.84g/mL) pre-cooled to 0°C with ice/ethanol bath, the temperature should be kept under 5°C. The resulting solution was cooled to−5°C and then was treated with a cold solution of 8mL of concentrated sulfuric acid (d=1.84g/mL) was added on 5.3mL of concentrated nitric acid (d=1.42g/mL), keeping the temperature below 0°C. After 15min, a mixture of 100g of ice and 150mL of water was added to promote the precipitation. A yellow precipitate of 3-nitroacetophenone was filtered out and recrystallized from ethanol. Yield: 55percent.
Reference：
[1] Patent: CN104193689, 2017, B, . Location in patent: Paragraph 0024; 0025; 0026; 0027; 0028; 0029
[2] Synthetic Communications, 2009, vol. 39, # 16, p. 2949 - 2953
[3] Synthetic Communications, 2011, vol. 41, # 19, p. 2946 - 2951
[4] RSC Advances, 2013, vol. 3, # 40, p. 18609 - 18613
[5] Patent: CN106242957, 2016, A, . Location in patent: Paragraph 0028; 0035; 0042
[6] Tetrahedron Letters, 2004, vol. 45, # 47, p. 8681 - 8683
[7] Patent: CN105622615, 2016, A, . Location in patent: Paragraph 0117; 0118; 0119
[8] European Journal of Medicinal Chemistry, 2013, vol. 67, p. 142 - 151
[9] Journal of the Society of Chemical Industry, London, 1923, vol. 42, p. 462 T[10] Chem. Zentralbl., 1924, vol. 95, # I, p. 1028
[11] Journal of the Chemical Society, 1935, p. 299,301[12] Chemische Berichte, 1936, vol. 69, p. 16,17
[13] Journal of Organic Chemistry, 1947, vol. 12, p. 617,680
[14] Journal of the American Chemical Society, 1934, vol. 56, p. 1369
[15] Journal of the Chemical Society, 1935, p. 1167,1172
[16] Journal of the Society of Chemical Industry, London, 1933, vol. 55, p. 29 T
[17] Pr. S. Dakota Acad., 1945, vol. 25, p. 64
[18] Journal of the Chemical Society, 1931, p. 314,315, 317
[19] Chemische Berichte, 1901, vol. 34, p. 1691
[20] Chemische Berichte, 1901, vol. 34, p. 3522
[21] Zeitschrift fuer Elektrochemie und Angewandte Physikalische Chemie, 1903, vol. 9, p. 429
[22] Journal fuer Praktische Chemie (Leipzig), 1921, vol. <2> 101, p. 209
[23] Chemische Berichte, 1901, vol. 34, p. 3522
[24] Organic Syntheses, 1930, vol. 10, p. 74[25] Organic Syntheses, 1931, vol. 11, p. 102
[26] Acta Crystallographica Section C: Crystal Structure Communications, 1997, vol. 53, # 4, p. 474 - 476
[27] Monatshefte fur Chemie, 2007, vol. 138, # 5, p. 449 - 452
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[29] Catalysis Letters, 2011, vol. 141, # 12, p. 1814 - 1820
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium <i>tert</i>-butylate; copper(I) triflate; 5-[(2S)-pyrrolidine-2-yl]-1H-tetrazole In N,N-dimethyl-formamide at 25℃; for 1.5 h;
General procedure: A round-bottom flask was charged with alcohol (2 mmol), CuOTf (0.1 mmol, 0.05 equiv) (S)-5-(pyrrolidin-2-yl)-1H-tetrazole (0.1 mmol, 0.05 equiv), TEMPO (0.1 mmol, 0.05 equiv), t-BuOK (2 mmol, 1 equiv) and DMF (5 ml). The reaction mixture was stirred at 25 °C open to air until the completion of the reaction, as monitored by TLC. The mixture was then diluted with CH2Cl2 (20 ml), washed with water, dried over Na2SO4, and evaporated under vacuum to give the crude product, which was purified by column chromatography to give the pure product.
95%
With dihydrogen peroxide; acetic acid; sodium bromide In water at 60℃; for 2 h; Inert atmosphere
General procedure: Under nitrogen atmosphere, to a solution of substrate alcohol (0.5 mmol) in aceticacid (1.0 mL) was added a stock-solution of aqueous NaBr solution (1.94 M, 25 μL)and 30percent aqueous H2O2 (50 μL, 0.5 mmol). After stirring the mixture for one hour at60 °C, additional 30percent aqueous H2O2 (50 μL, 0.5 mmol) was added, and stirring wascontinued for another one hour. After cooling, the mixture was poured into a saturatedaqueous NaHCO3 solution (ca. 30 mL) with the aid of CH2Cl2, and resulting mixturewas extracted with CH2Cl2. The combined organic layers were dried over anhydrousMgSO4, filtered and concentrated in vacuo. The residue was chromatographed onsilica gel (flash column or preparative TLC) to afford the corresponding ketone.
90%
With 1-methyl-1H-imidazole; [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrakis(acetonitrile)copper(I) trifluoromethanesulfonate; sodium chloride In neat (no solvent)Milling; Green chemistry
General procedure: 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO, 9.4 mg,0.06 mmol, 3 mol percent), 2,2′-bipyridyl (9,4 mg, 0.06 mmol,3 mol percent), [Cu(CN)4]OTf (22.6 mg, 0.06 mmol, 3 mol percent) and1-methylimidazole (NMI, 11.5 mg, 11.2 μL, 0.14 mmol,7 mol percent) were placed in a zirconia-milling beaker (45 mL)equipped with four balls (two balls × 5 mm , two balls ×12 mm ) of the same material. The jar was sealed and ballmilled for 1 min. Then, benzyl alcohol (216.3 mg, 207 μL,2.0 mmol), NaCl (1.0 g) together with other two zirconia balls(12 mm ) were added and the reaction mixture was subjectedto grinding for further 10 minutes overall (two cycles of5 minutes each). The first milling cycle was followed by a breakof 2 min leaving in the meantime the uncovered jar in open air.The progress of the reaction was monitored by TLC analysis(heptane/AcOEt 9:1 v/v) and GC–MS analysis on an aliquot ofthe crude. Upon completion of the ball milling process, the jarwas opened, the milling balls were removed and the resultingcrude product (adsorbed on NaCl) was then easily transferredinto a separating funnel filled with an aqueous 10percent citric acidsolution (20 mL). The aqueous phase was extracted withcyclopentyl methyl ether (or alternatively with AcOEt)(3 × 15 mL). The combined organic fractions were washed withH2O (25 mL) and brine (25 mL), then dried over Na2SO4, andconcentrated in vacuo to give benzaldehyde in high yield (195 mg, 92percent) and good purity (>93percent by GC analysis). Alternatively, after completion of the reaction, the resulting crudeproduct (adsorbed on NaCl) can be also easily purified by ashort column chromatography on silica gel using heptane/ethylacetate (9:1 v/v) as the eluents to afford pure aldehyde 2b inhigh yield (202 mg, 95percent) as a colourless liquid.
87%
at 75℃; for 1.66667 h;
General procedure: A mixture of alcohols (1 mmol) and DBDMH or DCDMH (1-1.5 mmol) in a 10 mL round-bottomed flask sealed with a stopper, was stirred in an oil-bath for the appropriate time and temperature (Table 1) under solvent-free condition. Then, as monitored by TLC (eluent n-hexane/acetone 10:2), hot water (10 mL) was added to mixture and stirred magnetically for 10 min. Then, the solution was extracted with (CH2Cl2/water (2 × 10 mL)) and organic phase dried over anhydrous Na2SO4 (1 g). Evaporation of the solvent gave the corresponding carbonyl compounds. Melting points and spectral data of all products are fully consistent with those previously reported. The structures of the products were confirmed from physical and spectroscopic data such as melting points, 1H NMR and 13C NMR spectra, fully consistent with those previously reported.17,18
70%
With 1-hydroxy-1H-1,2,3-benziodoxathiole 1,3,3-trioxide; Oxone; cetyltrimethylammonim bromide In water at 20℃; for 2 h; Green chemistry
General procedure: The alcohol (2 mmol) was added to a solution of IBS (0.02 mmol, 0.01 eq), oxone (2.2 mmol, 1.1 equiv.) and 3 wtpercent CTAB solution (5 mL). The mixture was stirred at room temperature. The reaction was monitored by TLC. After completion, the solution was extracted with CH2Cl2 (3 × 10 mL). The combined organic phase was then filtered through a pad of silica gel and evaporated under vacuum to afford the desired product.
62%
With tert.-butylhydroperoxide; eosin y In decane; acetonitrile at 25℃; for 72 h; Inert atmosphere; Irradiation; Molecular sieve; Green chemistry
General procedure: Oven dried round bottom flask was charged with Eosin Y (5 mmol) alcohol (1 mmol) and 3 equiv. of TBHP (5.5 M in decane) in dry ACN. The resulting mixture was degassed for 15 mins, followed by back filling N2, and then irradiated under Blue LED light (12W, 455 nm) at room temperature (25 oC). After reaction completion monitored through TLC, the mixture was diluted with 15 ml of 10percent NaHCO3 solution, and extracted with EtOAc (3 × 20 ml). The combined organic extracts were washed with brine (20 ml), dried over Na2SO4, and concentrated on vacuo. Purification of the crude product on silica gel using EtOAc:Hexane as solvent system afforded the desired product.
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13
[ 13331-27-6 ]
[ 75-05-8 ]
[ 121-89-1 ]
Yield
Reaction Conditions
Operation in experiment
70%
With 1,10-Phenanthroline; nickel(II) bromide 2-methoxyethyl ether; sodium hydrogencarbonate In water at 100℃; for 5 h; Autoclave
General procedure: The reaction was carried out in an autoclave containing a 10 mL Teflon reactiontube. NiBr2·diglyme (5 molpercent), 1,10-phen (10 molpercent) and a magnetic stir bar wereplaced in the tube. Then, arylboronic acid (1.0 mmol), NaHCO3 (2.0 equiv), H2O (2.0mmol) and alkyl nitrile (1.0 mL) were added to the tube. After that the autoclave wascapped with a stopper. The autoclave was cool down by liquid nitrogen, then createdvacuum at this temperature and added HCFC-244bb (2.0 mL, 2.6 g) by self-suction.Finally the autoclave was wormed in an oil bath at 100 °C for 5 h. After the reaction,the autoclave was cooled to room temperature and vented the excess HCFC-244bb carefully. Water (30 mL) was added to the mixture, and the mixture was extractedwith dichloromethane (3 x 15 mL). The organic layers were washed with brine, driedover Na2SO4, and evaporated the organic solvent by rotatory evaporator. The crudeproduct was then purified by column chromatography.
With mercuric triflate In ethanol at 20℃; for 24 h;
Representative experimental procedure: To a solution of phenylacetylene (225 mg, 2.2 mmol) in 3 mL ethanol, o-phenylenediamine (108 mg, 1.0 mmol) and Hg(OTf)2 (10 mg, 0.02 mmol) were added and stirred at room temperature for 6.5 h. Completion of the reaction was monitored by TLC. After completion of reaction, the reaction mixture was quenched with water, extracted with dichloromethane, dried over anhydrous sodium sulphate, and volatiles were removed. The crude residue was purified by short column chromatography over silica-gel (60-120 mesh) using 5percent ethylacetate/petroleum ether mixture afforded 2-methyl-2,4-diphenyl-2,3-dihydro-1H-benzo[b][1,4]diazepine (3aa) (281 mg, 90percent) as a yellow crystalline solid
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[ 121-89-1 ]
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[ 121-89-1 ]
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[ 121-89-1 ]
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[ 121-89-1 ]
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[ 121-89-1 ]
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[ 121-89-1 ]
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[ 7394-18-5 ]
[ 121-89-1 ]
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[ 121-89-1 ]
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61
[ 121-89-1 ]
[ 5400-78-2 ]
Yield
Reaction Conditions
Operation in experiment
98%
Stage #1: With nickel boride In water; acetonitrile at 20℃; for 0.0833333 h; Green chemistry Stage #2: With sodium tetrahydroborate In water; acetonitrile at 20℃; for 0.0166667 h; Green chemistry
General procedure: In a round-bottomed flask (10 mL) equipped with a magneticstirrer, a mixture of nitrobenzene (0.123 g, 1 mmol)and H2O (2 mL) was prepared. Ni2B (0.006 g, 0.05 mmol) was then added and the mixture was stirred for 5 min.NaBH4 (0.095 g, 2.5 mmol) was also added and the resultingmixture was continued to stirring for 3 min at roomtemperature. TLC monitored the progress of the reaction(eluent, n-hexane/Et2O:5/3). After completion of the reaction,aqueous solution of KOH (2 percent, 5 mL) was addedand the mixture was stirred for 10 min. The mixture wasextracted with EtOAc (3 × 8 mL) and then dried overanhydrous Na2SO4. Evaporation of the solvent affords thepure liquid aniline in 95 percent yield (0.088 g, Table 2, entry 1).
96%
With sodium tetrahydroborate In water at 60 - 70℃; for 0.1 h; Green chemistry
General procedure: In a round-bottom flask (10 mL) containing 2 mL water, a mixture of nitrobenzene (0.123 g, 1 mmol) and Fe3O4SiO2Cu–Ni–Fe–Cr LDH (10 mg) was prepared and the resulting mixture was stirred for 5 min. Next, NaBH4(0.076 g, 2 mmol) was added and the reaction mixture was stirred magnetically for 3 min under oil bath conditions (60–70 °C). TLC monitored the progress of the reaction (eluent, n-hexane/EtOAc: 5/2). After completion of the reduction reaction, the mixture was cooled to the room temperature. EtOAc (3 mL) was then added and the resulting mixture was again stirred for 10 min. The magnetic nanocatalyst was separated by an external magnet followed by extraction with EtOAc (2 × 5 mL). The combined organic layers were dried over anhydrous Na2SO4. Evaporation of the solvent afforded the pure liquid aniline in 95percent yield (Table 2, entry 1).
95%
With sodium tetrahydroborate In methanol at 0℃; for 1 h;
1-(3-Nitrophenyl)ethanol (ID30) To a solution of 1-(3-nitrophenyl)ethanone (ID29, 2.32 g, 14.0 mmol) in MeOH (100 mL) at 0° C. was added NaBH4 (2.20 g, 58.2 mmol) and the resulting mixture was allowed to stir at 0° C. for 1 h. After concentration, the residue was diluted with EtOAc (150 mL) and water (50 mL) and the organic layer was washed with water (50 mL), brine (50 mL), and dried over Na2SO4. After filtration, the filtrate was concentrated and the residue was dried in vacuo to give compound ID30 as a yellowish oil (2.23 g, 95percent). 1H NMR (CDCl3, 600 MHz) δ 8.25 (s, 1H), 8.12 (ddd, J=8.4, 1.2, 1.2 Hz, 1H), 7.72 (d, J=7.2 Hz, 1H), 7.52 (dd, J=8.1, 8.1 Hz, 1H), 5.02 (q, J=6.6 Hz, 1H), 2.07 (s, 1H), 1.54 (d, J=6.6 Hz, 3H).
92%
With 2BH4(1-)*Zn(2+)*Cl2Na2 In acetonitrile at 20℃; for 0.666667 h;
General procedure: In a round-bottomed flask (10 mL), equipped with a magneticstirrer bar, a solution of acetophenone (0.121 g, l mmol) was prepared in CH3CN(3 mL). To this solution, Zn(BH4)2/2NaCl (0.210 g,1 mmol) was added. The resulting mixture was stirred at room temperature for 60 min. The reaction was monitored by TLC(eluent; Hexane/EtOAc: 10/1). After completion of the reaction, distilled water (5 mL) was added to the reaction mixture and stirred for 5 min. The mixture was extracted with CH2Cl2 (3 ×8 mL) and dried over anhydrous Na2SO4. Evaporation of the solvent followed column chromatography of the resulting crude material over silica gel (eluent; Hexane/EtOAc: 10/1) afforded crystals of 1-phenylethanol (0.l1 g, 93 percent yield,Table 2, entry 11).
90%
With sodium borohydrid In ethanol
EXAMPLE 3 1-(m-Nitrophenyl)ethyl monate A A solution of sodium borohydride (0.4 g, 10 mmol) in ethanol (10 ml) was treated with m-nitroacetophenone (3.3 g, 20 mmol) at 20° C. for 20 mins. The solution was the diluted with aqueous potassium carbonate and extracted with chloroform. The extracts were dried (magnesium sulphate) and evaporated in vacuo to give 1-(m-nitrophenyl)ethanol as an oil (2.9 g, 90percent);
67 %Chromat.
With sodium hydroxide In isopropyl alcohol at 82℃; for 0.75 h;
General procedure: In a typical procedure, a 5 mg (0.77 molpercent) of RuO2/MWCNT and 80 mg (2 mmol) of NaOH were stirred with 5 mL of i-PrOH taken in an ace pressure tube equipped with a stirring bar. Then the substrate (1 mmol) was added to the stirring solution and then the mixture was heated at 82°C. The completion of the reaction was monitored by GC. After the reaction, the catalyst was separated out from the reaction mixture by simple centrifugation and the products and unconverted reactants were analyzed by GC without any purification. Selectivity of the product for each reaction was alsocalculated. Finally, the separated RuO2/MWCNT was washed well with diethyl ether followed by drying in an oven at 60°C for 5 h and it was reused for the subsequent transfer hydrogenation of carbonyl compounds to investigate the reusability of the RuO2/MWCNT.
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[13] Patent: US2016/376238, 2016, A1, . Location in patent: Paragraph 0363
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70
[ 121-89-1 ]
[ 2454-37-7 ]
Yield
Reaction Conditions
Operation in experiment
94%
Stage #1: With nickel boride In water for 0.0833333 h; Green chemistry Stage #2: With sodium tetrahydroborate In water at 20℃; for 0.0666667 h; Green chemistry
General procedure: In a round-bottomed flask (10 mL) equipped with a magneticstirrer, a mixture of nitrobenzene (0.123 g, 1 mmol)and H2O (2 mL) was prepared. Ni2B (0.006 g, 0.05 mmol) was then added and the mixture was stirred for 5 min.NaBH4 (0.095 g, 2.5 mmol) was also added and the resultingmixture was continued to stirring for 3 min at roomtemperature. TLC monitored the progress of the reaction(eluent, n-hexane/Et2O:5/3). After completion of the reaction,aqueous solution of KOH (2 percent, 5 mL) was addedand the mixture was stirred for 10 min. The mixture wasextracted with EtOAc (3 × 8 mL) and then dried overanhydrous Na2SO4. Evaporation of the solvent affords thepure liquid aniline in 95 percent yield (0.088 g, Table 2, entry 1).
94%
With sodium tetrahydroborate; copper In water at 80℃; for 0.133333 h; Green chemistry
General procedure: In a round-bottom flask (10 mL) equipped with a magneticstirrer, a mixture of nitrobenzene (0.123 g, 1 mmol)and H2O (2 mL) was prepared. Cu NPs (0.0095 g,15 mmol percent) was then added, and the mixture was stirredfor 3 min at 80 °C. Afterward, NaBH4 (0.076 g, 2 mmol)was added portion wisely (two portions) with the intervalof 2 min, and the resulting mixture was continued to stirringat 80 °C. TLC monitored the progress of the reaction(n-hexane/EtOAc: 5/2). After completion of the reaction,Cu NPs was separated by filtration, and the mixture wasextracted with EtOAc (2 × 5 mL). The organic layer wasthen dried over anhydrous Na2SO4. Evaporation of the solventaffords the pure liquid aniline in 91 percent yield (0.085 g,Table 2, entry 1).
94%
Stage #1: With Cu(OH)x impregnated on Fe3O4 In water for 0.0833333 h; Green chemistry Stage #2: With sodium tetrahydroborate In water at 55 - 60℃; for 0.2 h; Green chemistry
General procedure: In a round-bottom flask (10 mL) equipped with a magnetic stirrer, a mixture of nitrobenzene (0.123 g, 1 mmol) and H2O (3 mL) was prepared. Nano Fe3O4-Cu(OH)x(20 mg, 0.06 mmol, x = 2) was then added, and the resulting mixture was stirred for 5 min. Next, NaBH4 (0.076 g,2 mmol) was added and the reaction mixture was continued to stirring for 3 min at 55–60 °C. TLC monitored the progress of the reaction (eluent, n-hexane/EtOAc: 5/2). After completion of the reaction, the nanocatalyst was separated by an external magnet and the reaction mixture was extracted with EtOAc (2 × 5 mL). Drying organic layer over anhydrous Na2SO4 and then evaporation of the solvent affords the pure liquid aniline in 95 percent yield (0.088 g, Table 2, entry 1).
94%
With sodium tetrahydroborate In water at 60 - 70℃; for 0.3 h; Green chemistry
General procedure: In a round-bottom flask (10 mL) containing 2 mL water, a mixture of nitrobenzene (0.123 g, 1 mmol) and Fe3O4SiO2Cu–Ni–Fe–Cr LDH (10 mg) was prepared and the resulting mixture was stirred for 5 min. Next, NaBH4(0.076 g, 2 mmol) was added and the reaction mixture was stirred magnetically for 3 min under oil bath conditions (60–70 °C). TLC monitored the progress of the reaction (eluent, n-hexane/EtOAc: 5/2). After completion of the reduction reaction, the mixture was cooled to the room temperature. EtOAc (3 mL) was then added and the resulting mixture was again stirred for 10 min. The magnetic nanocatalyst was separated by an external magnet followed by extraction with EtOAc (2 × 5 mL). The combined organic layers were dried over anhydrous Na2SO4. Evaporation of the solvent afforded the pure liquid aniline in 95percent yield (Table 2, entry 1).
92%
Stage #1: at 20℃; for 0.05 h; Green chemistry Stage #2: With glycerol In water at 20℃; for 0.666667 h; Green chemistry
General procedure: In a round-bottom flask (10 mL) equipped with a magneticstirrer, a mixture of nitrobenzene (1 mmol, 0.123 g) and H2O(2 mL) was prepared. Fe3O4(at)APTMS(at)ZrCp2 (7 mg)was then added and the resulting mixture was stirred for 3 min. Next, glycerol (2 mmol) was added and the reaction mixture was stirred for 40 min at room temperature. TLC monitored the progress of the reaction (eluent, n-hexane/EtOAc: 5/2). After completion of the reaction, the catalyst mixture was extracted with EtOAc (2 × 5 mL). Drying organiclayer over anhydrous Na2SO4followed by evaporation of the solvent affords pure liquid aniline in 96percent yield (0.089 g,Table 3, entry 1).
53%
With hydrogen In water
EXAMPLE I m-Nitroacetophenone [123.8 g., 0.75 mole, 99percent purity by gas-liquid chromatography (GLC)], water (450 ml.) and Raney nickel catalyst (40 g. (wet) Grace No. 4200) was charged to a 1 liter Parr stirring autoclave. The reaction mass was stirred at 100 psi constant hydrogen pressure while the temperature was adjusted slowly to 99° C (the exotherm of hydrogenation contributed initially to the temperature increase from ambient, 26° C). After 4 hours there was no further evidence of hydrogen absorption. The hydrogenate was filtered at 60°-70° C and the clear, light amber colored filtrate was cooled to 10° C with stirring. After stirring one hour, the original filtrate was again filtered to give 54.5 g. of m-amino-α-methylbenzyl alcohol (53.0percent yield) which was 100percent pure by GLC.
Reference：
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[9] Journal of the Chemical Society of Pakistan, 2016, vol. 38, # 4, p. 679 - 684
[10] Patent: US4021487, 1977, A,
[11] Patent: US4021487, 1977, A,
[12] Patent: US4024187, 1977, A,
[13] Arzneimittel Forschung, 1958, vol. 8, p. 532,536
[14] Journal of Organic Chemistry, 1946, vol. 11, p. 405,412
[15] Patent: US4024187, 1977, A,
[16] Patent: US4024187, 1977, A,
[17] Organic and Biomolecular Chemistry, 2012, vol. 10, # 36, p. 7321 - 7326
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71
[ 121-89-1 ]
[ 1314911-01-7 ]
[ 2454-37-7 ]
[ 99-03-6 ]
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72
[ 121-89-1 ]
[ 2454-37-7 ]
[ 76116-24-0 ]
[ 103966-65-0 ]
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73
[ 7787-71-5 ]
[ 121-89-1 ]
[ 127413-59-6 ]
Yield
Reaction Conditions
Operation in experiment
85%
With bromine; sodium sulfite In 1,1,2-Trichloro-1,2,2-trifluoroethane
EXAMPLE 15 A vigorously stirred mixture consisting of 2.5 ml (0.05 mole) of bromine trifluoride and 3.2 ml (0.056 mole) of bromine was added into an ice-water cooled three necked flask equipped with a magnetic stirrer and a condenser, containing a suspension of 36 gr (0.2 mole) 3-nitroacetophenone in 80 ml of freon 113. The addition was carried out dropwise with vigorous stirring while the temperature was kept under 20° C. After the addition was completed the crude reaction mixture was poured into a stirred icy 5percent sodium sulfite solution. The organic layer was separated and the aqueous solution was extracted twice with 100 ml dichloromethane. The combined organic layer was washed with 5percent sodium bicarbonate solution and successively with water. The organic phase was dried over anhydrous magnesium sulphate and the solvent evaporated. The residue was distilled under reduced pressure in order to get rid of unreacted substrate. The residue was recrystallized from toluene. 7.3 gr of 3-bromo-5-nitroacetophenone were obtained, 85percent yield based on reacted substrate.
Reference：
[1] Patent: US4954648, 1990, A,
74
[ 121-89-1 ]
[ 127413-59-6 ]
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[1] Journal of Organic Chemistry, 1993, vol. 58, # 1, p. 239 - 240
[2] Synlett, 2013, vol. 24, # 5, p. 603 - 606
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 3, p. 1281 - 1297
75
[ 4637-24-5 ]
[ 121-89-1 ]
[ 115955-48-1 ]
Yield
Reaction Conditions
Operation in experiment
89%
at 140℃; for 12 h;
In a 250 mL round bottom flask was added 16.5 g (100 mmol) of 3-nitroacetophenone, 26.5 mL of N,N-dimethylformamide dimethyl acetal (200 mmol) and 100 mL of xylene. The mixture was heated to 140°C for 12 hours. Then the reaction mixture was cooled to room temperature and the formed precipitate was filtered off, washed with petroleum ether and diethyl ether followed by purification by chromatography using ethyl acetate/cyclohexene (25/75) to afford 19.6 g of a yellow solid. Yield: 89percent. 1H NMR (200 MHz, DMSO-d6) δ 8.59 (t, 1H), 8.42 – 8.23 (m, 1H), 7.81 (d, J = 12.1 Hz, 1H), 7.70 (t, J = 7.9 Hz, 1H), 5.89 (d, J = 12.1 Hz, 1H), 3.17 (s, 1H), 2.95 (s, 1H). 13C NMR (50 MHz, DMSO-d6) δ 182.8, 155.2, 147.9, 141.6, 133.4, 129.8, 125.1, 121.5, 90.3, 44.7, 37.3.
79%
Heating / reflux; Neat (no solvent)
3-Nitroacetophenone (5.0 g, 30.3 mmol) in dimethylformamide-dimethylacetal (10 mL) is heated at reflux overnight. The reaction mixture is cooled to room temperature and evaporated to remove the volatiles. The residue is slurried in ethyl ether and the suspension is filtered and washed with ether to give 10.5 g (79percent) of 3-(dimethylamino)-1-(3-nitrophenyl)-2-propen-1-one, 104-105° C.
79%
Heating / reflux
3-Nitroacetophenone (5.0g, 30.3 mmol) in dimethylformamide-dimethylacetal (10 mL) was heated at reflux overnight. The reaction mixture was cooled to room temperature and evaporated to remove the volatiles. The residue was slurried in ethyl ether and the suspension was filtered and washed with ether to give 10.5 g (79percent) of 3-(dimethylamino)-1-(3-nitrophenyl)-2-propen-1-one, 104-105° C.
79%
Heating / reflux
3-Nitroacetophenone (5.0g, 30.3 mmol) in dimethylformamide-dimethylacetal (10 mL) was heated at reflux overnight. The reaction mixture was cooled to room temperature and evaporated to remove the volatiles. The residue was slurried in ethyl ether and the suspension was filtered and washed with ether to give 10.5 g (79percent) of 3-(dimethylamino)-1-(3-nitrophenyl)-2-propen-1-one, 104-105° C.
79%
Heating / reflux
Step 1: 3-(Dimethylamino)-1-(3-nitrophenyl)-2-propen-1-one 3-Nitroacetophenone (5.0 g, 30.3 mmol) in dimethylformamide-dimethylacetal (10 mL) is heated at reflux overnight. The reaction mixture is cooled to room temperature and evaporated to remove the volatiles. The residue is slurried in ethyl ether and the suspension is filtered and washed with ether to give 10.5 g (79percent) of 3-(dimethylamino)-1-(3-nitrophenyl)-2-propen-1-one, 104-105° C.
11.34 g
for 21 h; Reflux
10 g of 3-nitroacetophenone (60.6 mmol, 1 equiv.), 35.63 g of N, N-dimethylformamide dimethylacetal (181 mmol, 3 equiv.), and 50 ml of xylene were refluxed overnight (21 hours), a little raw material was not reacted and the reaction was stopped. The reaction solution was cooled and concentrated to remove xylene. 150 ml of petroleum ether was added to the residue, and a solid precipitated under stirring, followed by filtration to obtain 11.34 g of 3-dimethylamino-1-(3-nitrophenyl)-prop-2-en-1-one as a yellow solid.
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 8, p. 1780 - 1783
[2] Patent: US2007/219183, 2007, A1, . Location in patent: Page/Page column 11
[3] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 10, p. 2735 - 2738
[4] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 24, p. 6890 - 6892
[5] Patent: US2006/63784, 2006, A1, . Location in patent: Page/Page column 43
[6] Patent: US2006/63785, 2006, A1, . Location in patent: Page/Page column 48-49
[7] Patent: US2007/219186, 2007, A1, . Location in patent: Page/Page column 22
[8] Journal of Medicinal Chemistry, 1998, vol. 41, # 15, p. 2858 - 2871
[9] Patent: WO2009/90548, 2009, A2, . Location in patent: Page/Page column 38-39
[10] Patent: EP3287456, 2018, A1, . Location in patent: Paragraph 0154
76
[ 121-89-1 ]
[ 96605-66-2 ]
Reference：
[1] Patent: CN105622615, 2016, A,
77
[ 121-89-1 ]
[ 317830-29-8 ]
Reference：
[1] Journal of Enzyme Inhibition and Medicinal Chemistry, 2014, vol. 29, # 3, p. 408 - 419
With sodium hydroxide In ethanol; water for 4h; Cooling with ice;
Preparation of the Chalcones
General procedure: An Illustrative Procedure with (E)-1-Aryl-3-(2-pyrrolyl)-2-propenones (3k). 2-Pyrrolecarbaldehyde (12 mmol), acetophenone (13 mmol), and 24 mmol of NaOH in ethanol (20 mL) and water (10 mL) were mixed in an ice-bath and stirred for 4 h in the bath. The mixture was neutralized with 1 M-HCl aqueous solution to pH 8-9. The resulting precipitate was collected and recrystallized from ethanol.
87%
With silica-gel-supported sulfuric acid In neat (no solvent) at 65℃; for 1.5h;
3.5. Representative Procedure for the SSA Catalysed Synthesis of Chalcones
General procedure: The SSA (0.02 g) was added to a well stirred suspension of PhAc (1 mL, 0.90 g, 7.53 mmol, 1 eq.) and PhCHO (0.84 g, 7.91 mmol, 1.05 eq.) and the resulting mixture was heated at 65 °C for 1.5 h. The reaction mixture was cooled to room temperature and partitioned between brine (25 mL) and CH2Cl2 (3 × 15 mL) and solid SSA was filtered off. The SSA was washed with acetone (25 mL) to ensure desorption of product on SSA surface. The combined organic extract was washed with brine (3 × 25 mL) and the organic extract was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the chalcone as colorless solid (1.48 g, 91%).
With sodium hydroxide
With sodium hydroxide In ethanol; water at 20℃; Cooling with ice;
With cobalt(II) stearate; sodium carbonate; sodium hydroxide; at 140 - 165℃; under 6000.6 Torr; for 20.0h;pH 7 - 8.5;
The 3000Kg-nitro ethylbenzene, 150g cobalt stearate into the oxidation reactor, was evacuated and replaced with oxygen, to the oxidation reactor through the oxygen control oxygen pressure 0.8Mpa, open stirred reactor, open the oxidation reactor steam the reaction was terminated heating, when the oxidation reaction Tanei Da to 165 , after the reaction started off steam, exhaust steam, open the cooling water, a slow cooling to 140 , 140 thermal control for 18 hours, when the amount of ketone containing up to 80% when with the kettle and pressure oil to oxidation reaction to acid tank, acid tank to start stirring slowly added 30% sodium hydroxide solution 100Kg, adjusted PH to 7, then add a saturated solution of sodium carbonate 30Kg, adjusted PH to 8.5, stirred for 30 minutes, allowed to stand for 1.5 hours to stop stirring, layered sodium nitrobenzene solution put to the reservoir, between nitrobenzoic acid to be recovered, the oxidation reaction of oil to the crystallization reactor, cooling to freeze 10 , centrifugal rejection filter , washing, drying in 2350kg (Melting point 78.5 ), distilled liquor recovered 495kg (including the amount of 19.16% ketone, and then for the oxidation), inter-nitroacetophenone product yield 85.85%.
60%
With copper; Selectfluor; In water; acetonitrile; at 20℃; for 4.0h;
m-Nitroethylbenzene 0.2 mmol,Copper powder 0.02 mmolAnd Selectfluor 0.02mmol in turn into a 10mL pressure sealed container,Add 2 mL of a mixture of acetonitrile and water (CH3CN/H2O = 400:1).The mixture was stirred at room temperature and the reaction was monitored by TLC. The reaction was completed after 4 hours.The reaction solution was diluted with dichloromethane 10 mL,Filtered to obtain a clear solution, after distillation of the solvent, column chromatography(eluent ratio: petroleum ether to ethyl acetate volume ratio 20:1) separation,The washings were collected and the solvent was evaporated to give m-nitroacetophenone in a yield of 60%.
With methanol; [Co((dimethylglyoximate)BF2)2•2H2O] at 65℃; for 49h; Sealed tube; Neutral conditions; regioselective reaction;
91%
With C22H20AuN3O2P(1+)*CF3O3S(1-); water; silver trifluoromethanesulfonate; acetic acid at 100℃; for 10h;
88%
With silver trifluoromethanesulfonate In water; acetic acid at 110℃; for 6h; Schlenk technique;
2.6 Hydration of alkynes
General procedure: To a 25mL Schlenk tube, AuSBA-15 (6wt%, 20mg), AgOTf (0.05mmol) was added to a solution of phenylacetylene (1.0mmol) in HOAc/H2O (3.0mL, 15:1) under ambient air, the resulting mixture was stirred for 6hat 110°C. It was monitored by TLC. After the reaction was completed, the solvent was removed under reduced pressure and purified of the crude product by column chromatography on silica-gel afforded the desired compound.
83%
With Perfluorooctanesulfonic acid; C8AgF17O3S*H2O In water at 100℃; for 8h; Darkness; regioselective reaction;
3.3. Typical procedure for synthesis of ketones
General procedure: To the mixture of phenylacetylene (1 mmol), water (3.0 mL),silver perfluorooctanesulfonate (5 mol%) and perfluorooctane sulfonateacid (2 mol%) was added. The mixture was stirred at 100 Cfor 8 h. The solution was extracted with n-hexane (diethyl ether)(3 5 mL), the combined extract was dried with anhydrous MgSO4. The rest of the solution was used for the next cycle of reaction. Theextraction solvent was removed and the crude product was separatedby column chromatography to give the pure sample.
66%
With ethyl 2-hydroxypropionate; water at 110℃; Green chemistry;
3.3. General process for alkyne hydration to form compounds 2
General procedure: Alkynes (2mmol) were added to a stirred 35mL solution of EL:H2O(1:3). The reaction mixture was stirred at 110 °C for a suitable time.After successful conversion, the resultant solution was cooled to roomtemperature and extracted with ethyl acetate (4-6 mL). The combinedorganic phaseswere dehydrated over anhydrous sodium sulfate and filtered.The filtered solution was concentrated under reduced pressureand purified by column chromatography on silica gel (hexane:EtOAcas the eluent) to provide the pure desired product
With sulfuric acid
With cis-dichlorido[1-(3-sodiumsulfonatepropyl)-3-(2,4,6-trimethylphenyl)imidazol-2-ylidene](dimethylsulfoxide)platinum(II); water at 80℃; for 24h; Inert atmosphere; Schlenk technique;
With silica-gel-supported sulfuric acid In neat (no solvent) at 65℃; for 1.5h;
3.5. Representative Procedure for the SSA Catalysed Synthesis of Chalcones
General procedure: The SSA (0.02 g) was added to a well stirred suspension of PhAc (1 mL, 0.90 g, 7.53 mmol, 1 eq.) and PhCHO (0.84 g, 7.91 mmol, 1.05 eq.) and the resulting mixture was heated at 65 °C for 1.5 h. The reaction mixture was cooled to room temperature and partitioned between brine (25 mL) and CH2Cl2 (3 × 15 mL) and solid SSA was filtered off. The SSA was washed with acetone (25 mL) to ensure desorption of product on SSA surface. The combined organic extract was washed with brine (3 × 25 mL) and the organic extract was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the chalcone as colorless solid (1.48 g, 91%).
With sodium hydroxide; ethanol
With sodium hydroxide In methanol at 20℃; for 2h;
Microwave irradiation;
With potassium hydroxide In methanol; water at 0 - 20℃;
With hydrogenchloride; acetic acid at 20℃; for 12h;
Synthesis
General procedure: The chalcone derivatives with nitro groups were synthesized by Claisen-Schmidt condensation in acid-catalysed reaction (Scheme 1) as nitro compounds were found to decompose in the base catalysed reaction. 0.02 mol of aldehyde and 0.02 mol of ketones (4-nitroacetophenone or 3-nitroacetophenone) were added to round-bottom flask containing 20 ml acetic acid saturated with HCl gas. The reaction mixture was then stirred at room temperature for 12 hrs. The progress of the reaction was monitored by TLC. On the completion of reaction, the contents were poured in ice cold water and the product was filtered. The solid obtained was washed with water till neutral to litmus. The crude chalcone was then dried and weighed and was recrystallized in chloroform-methanol (Furniss 1989) (Figs. 1, 2). In case of 4-N(CH3)2-4′-NO2, the contents of the reaction were neutralized with aq. NaOH before filtration.
With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide In neat (no solvent) at 80℃; for 1.5h;
17%
With iodine
With bromine
With bromine; chlorine
With iodine; chlorine
With iodine
With iodine
With halogen for 24h; Reflux;
Stage #1: thiourea; 3-Nitroacetophenone With bromine In ethanol for 2h;
Stage #2: In ethanol for 12h; Reflux;
With iodine at 100℃;
4.1.2. General procedure for preparation of aminothiazoleintermediates 9a-r
General procedure: A mixture of the appropriate aryl ketones, 1-cyclobutylethan-1-one or 1-(furan-2-yl)ethan-1-one (8a-r, 0.1 mol) and thiourea(0.20 mol), and iodine (0.1 mol) were heated for 5 h to thick mass at100 C. After the thick mass was cooled, methanol was added, thesolid was treated with water and filtered. The residue was dried invacuo yielding the hydriodide salt of the aminothiazole intermediates9a-r, which was suitable for use in the next reaction.
With bromine
With iodine at 110℃; for 12h;
With bromine
2-Amino-4-substituted phenyl-1,3-thiazoles(4A1-4K11)
General procedure: The thiazoles 4A1-4K11 were synthesized accordingto literature procedure[17] involving reaction of aromaticketones with thiourea in the presence of bromine.
General procedure: In a round-bottomed flask (10 mL) equipped with a magneticstirrer, a mixture of nitrobenzene (0.123 g, 1 mmol)and H2O (2 mL) was prepared. Ni2B (0.006 g, 0.05 mmol) was then added and the mixture was stirred for 5 min.NaBH4 (0.095 g, 2.5 mmol) was also added and the resultingmixture was continued to stirring for 3 min at roomtemperature. TLC monitored the progress of the reaction(eluent, n-hexane/Et2O:5/3). After completion of the reaction,aqueous solution of KOH (2 %, 5 mL) was addedand the mixture was stirred for 10 min. The mixture wasextracted with EtOAc (3 × 8 mL) and then dried overanhydrous Na2SO4. Evaporation of the solvent affords thepure liquid aniline in 95 % yield (0.088 g, Table 2, entry 1).
97%
With methanol; sodium tetrahydroborate; at 0 - 20℃; for 1.5h;
Methanol (50 mL) was sequentially added to a 100 mL third product vial, m-nitroacetophenone (6.6g, 40mmol, 1.0eq), cooled to 0 C, Sodium borohydride (2.16 g, 60 mmol, 1.5 eq) was added in portions and reacted at room temperature for 1.5 hours.TLC tracks the end of the reaction. Concentrated methanol,Add 50 mL of water to the system and extract twice with ethyl acetate (30 mL*2),The organic phases were combined, washed twice with saturated brine, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain 6.5 g of 1-(3-nitrophenyl)ethanol with a yield of 97%.
96%
With sodium tetrahydroborate; In water; at 60 - 70℃; for 0.1h;Green chemistry;
General procedure: In a round-bottom flask (10 mL) containing 2 mL water, a mixture of nitrobenzene (0.123 g, 1 mmol) and Fe3O4SiO2Cu-Ni-Fe-Cr LDH (10 mg) was prepared and the resulting mixture was stirred for 5 min. Next, NaBH4(0.076 g, 2 mmol) was added and the reaction mixture was stirred magnetically for 3 min under oil bath conditions (60-70 C). TLC monitored the progress of the reaction (eluent, n-hexane/EtOAc: 5/2). After completion of the reduction reaction, the mixture was cooled to the room temperature. EtOAc (3 mL) was then added and the resulting mixture was again stirred for 10 min. The magnetic nanocatalyst was separated by an external magnet followed by extraction with EtOAc (2 × 5 mL). The combined organic layers were dried over anhydrous Na2SO4. Evaporation of the solvent afforded the pure liquid aniline in 95% yield (Table 2, entry 1).
95%
With sodium tetrahydroborate; In methanol; at 0℃; for 1h;
1-(3-Nitrophenyl)ethanol (ID30) To a solution of 1-(3-nitrophenyl)ethanone (ID29, 2.32 g, 14.0 mmol) in MeOH (100 mL) at 0 C. was added NaBH4 (2.20 g, 58.2 mmol) and the resulting mixture was allowed to stir at 0 C. for 1 h. After concentration, the residue was diluted with EtOAc (150 mL) and water (50 mL) and the organic layer was washed with water (50 mL), brine (50 mL), and dried over Na2SO4. After filtration, the filtrate was concentrated and the residue was dried in vacuo to give compound ID30 as a yellowish oil (2.23 g, 95%). 1H NMR (CDCl3, 600 MHz) delta 8.25 (s, 1H), 8.12 (ddd, J=8.4, 1.2, 1.2 Hz, 1H), 7.72 (d, J=7.2 Hz, 1H), 7.52 (dd, J=8.1, 8.1 Hz, 1H), 5.02 (q, J=6.6 Hz, 1H), 2.07 (s, 1H), 1.54 (d, J=6.6 Hz, 3H).
92%
With 2BH4(1-)*Zn(2+)*Cl2Na2; In acetonitrile; at 20℃; for 0.666667h;
General procedure: In a round-bottomed flask (10 mL), equipped with a magneticstirrer bar, a solution of acetophenone (0.121 g, l mmol) was prepared in CH3CN(3 mL). To this solution, Zn(BH4)2/2NaCl (0.210 g,1 mmol) was added. The resulting mixture was stirred at room temperature for 60 min. The reaction was monitored by TLC(eluent; Hexane/EtOAc: 10/1). After completion of the reaction, distilled water (5 mL) was added to the reaction mixture and stirred for 5 min. The mixture was extracted with CH2Cl2 (3 ×8 mL) and dried over anhydrous Na2SO4. Evaporation of the solvent followed column chromatography of the resulting crude material over silica gel (eluent; Hexane/EtOAc: 10/1) afforded crystals of 1-phenylethanol (0.l1 g, 93 % yield,Table 2, entry 11).
90%
With sodium borohydrid; In ethanol;
EXAMPLE 3 1-(m-Nitrophenyl)ethyl monate A A solution of sodium borohydride (0.4 g, 10 mmol) in ethanol (10 ml) was treated with m-nitroacetophenone (3.3 g, 20 mmol) at 20 C. for 20 mins. The solution was the diluted with aqueous potassium carbonate and extracted with chloroform. The extracts were dried (magnesium sulphate) and evaporated in vacuo to give 1-(m-nitrophenyl)ethanol as an oil (2.9 g, 90%);
With sodium tetrahydroborate; In ethanol;
a) Synthesis of alpha-methl-3-nitrobenzenemethanol [R1=CH3, X1=X2=H in formula (XVI)] 33 g (199.8 mmol) of 1-(3-nitrophenyl)ethanone [R1=CH3, X1=X2=H in formula (XV)] was weighed and charged into a 500 ml of eggplant type flask, followed by the addition of 120 ml of ethanol. After cooling on an ice water bath, 4.2 g (111 mmol) of NaBH4 was added in portions and the mixture was reacted for 30 minutes under ice cooling bath and for 2 hours at room temperature. The resulting reaction liquid was concentrated by evaporator and the residue was washed with water to quantitatively obtain light brown oil of alpha-methyl-3-nitrobenzene methanol [R1=CH3, X1=X2=H in formula (XVI)].
With methanol; sodium tetrahydroborate;Cooling with ice;
Preparation of 2-(4-methylpiperazin-1-yl)ethyl {3-[1-(5,6-difluoro-2-oxobenzoxazol-3-yl)ethyl]phenyl}carbamate (?A27?)Step aPreparation of 1-(3-nitrophenyl)ethanol26.4 g (160 mmol) of 1-(3-nitrophenyl)ethanone are suspended in 270 ml of methanol, and 6.1 g (160 mmol) of sodium borohydride are added in portions with ice cooling. The reaction mixture is subsequently stirred for a further 3 h without cooling, diluted with 300 ml of dichloromethane and washed with 3×200 ml of water. The organic phase is dried over sodium sulfate and evaporated to dryness.Product: 26.15 g; HPLC: Rt=3.87 min (method A).
General procedure: All racemic alcohols except for the (R,S)-1-phenylethanol were prepared using the following procedure: a mixture of ketone (5 mmol) and sodium borohydride (10 mmol) in anhydrous methanol (50 mL) was stirred at room temperature for 30 min. Next, saturated NaHCO3 (50 mL) and CH2Cl2 (100 mL) were introduced, and the mixture was stirred at room temperature for another 10 min. The organic layer was removed, and the aqueous layer was extracted twice with 25 mL CH2Cl2. The combined organic layers were dried over anhydrous Na2SO4 and concentrated to give the corresponding crude alcohols. The crude alcohols were then chromatographed to afford pure products. The 1H NMR spectra of these products were in good agreement with the literature.
67%Chromat.
With sodium hydroxide; In isopropyl alcohol; at 82℃; for 0.75h;
General procedure: In a typical procedure, a 5 mg (0.77 mol%) of RuO2/MWCNT and 80 mg (2 mmol) of NaOH were stirred with 5 mL of i-PrOH taken in an ace pressure tube equipped with a stirring bar. Then the substrate (1 mmol) was added to the stirring solution and then the mixture was heated at 82C. The completion of the reaction was monitored by GC. After the reaction, the catalyst was separated out from the reaction mixture by simple centrifugation and the products and unconverted reactants were analyzed by GC without any purification. Selectivity of the product for each reaction was alsocalculated. Finally, the separated RuO2/MWCNT was washed well with diethyl ether followed by drying in an oven at 60C for 5 h and it was reused for the subsequent transfer hydrogenation of carbonyl compounds to investigate the reusability of the RuO2/MWCNT.
With sodium tetrahydroborate; In methanol; at 0℃; for 4h;
General procedure: To a solution of the corresponding ketone in methanol (0.60 M) was added sodiumborohydride (0.33 equiv.) and the resulting mixture was stirred for 2 h at 0 C. Afterstirring, additional sodium borohydride (0.33 equiv.) was added to the mixture tocomplete the transformation. After 2 h, water was added to quench the reaction, andthe mixture was extracted with diethyl ether (3 times). The extracts were dried overanhydrous MgSO4, filtered, and concentrated under reduced pressure. The residuewas chromatographed on silica gel to afford desired alcohol.
With methanol; sodium tetrahydroborate; at 0 - 20℃;
General procedure: Ten mmol of NaBH4 was added to a cooled (0C) solution of 2.5 mmol of each specific substrate(1a-1f, 1m and 1n) in 50 mL of methanol. After stirring for 10 min, the mixture was warmed to room temperature and stirred for another 3-4 h to complete the reduction. After quenching with 2 M HCl topH 7.0, the mixture was extracted with EtOAc (50 mL 3). The organic phases were washed withbrine, dried over Na2SO4, filtered and concentrated in vacuum. The residue was purified by flashchromatography on silica gel (eluent: EtOAc/PE 1:20) to give the racemic alcohol 2a-2f, 2m and 2n(see Supplementary Materials for NMR spectroscopic data).
With cadmium sulphide; ammsnium formate In lithium hydroxide monohydrate at 20℃; for 14h; Inert atmosphere; Irradiation; Sealed tube; chemoselective reaction;
100%
With lithium hydroxide monohydrate; oxalic acid; titanium(IV) dioxide for 3h; Irradiation; Inert atmosphere; Sealed tube; Green chemistry; chemoselective reaction;
General procedure: Nitro compounds (0.1 mmol under sunlight and 0.5 mmol under UV LED irradiation) were dissolved in PEG-400 (1.5 ml) and then 10 ml of water was added to the solution; commercial TiO2 (P25) (40 mg) and oxalic acid (1.5 equimolar) were added into a round bottom Pyrex flask (25 ml). The reaction mixture was degassed by Argon gas (20 min) and sealed with a septum. Afterwards, the flask was irradiated under stirring with sunlight or violet LED (see the data in Table 2). After the completion of the reaction according to GC monitoring, NaHCO3 was added to increase pH = 7 and the mixture was stirred at room temperature. The aqueous layer was extracted with EtOAc (2x10 ml). The organic layer was dried with sodium sulfate, filtered and evaporated in vacuum.
99%
With hydrogen In methanol at 70℃; for 4h;
1 Embodiment 1
The 2.0g nitro-acetophenone between, 0.2gPt/Bi2O3(Pt content is 0.2 wt %), 10 ml anhydrous methanol by adding 50 ml of a batch-type reactor, successively for substitution reaction of the nitrogen and hydrogen gas in the kettle 3-5 time, hydrogen is charged into the pressure to 1.0 MPa, the temperature under stirring to 70 °C, the stirring speed is 600-800 rotation/minute. If the total pressure is reduced to 0.5 MPa the following, the additional hydrogen to the initial pressure. 4h no longer changes the total pressure of the, stop stirring, cooling to room temperature. To the reaction mixture after centrifugal, is yellow at the bottom of the catalyst, is green supernatant (if a meta-nitro acetophenone conversion is not complete, then the supernatant is a yellow-green, by-product with the nitro portion of the hydrogenation product is nitroso compound). Heating a small amount of supernatant using gas chromatographic analysis, a meta-nitro acetophenone conversion is greater than 99.9%, m-aminoacetophenone selectivity is greater than 99.9% (Figure 3). Rotary evaporation of the filtrate is removed by methanol to obtain the product m-aminoacetophenone, separation yield 99%
99%
With hydrogen In ethanol at 90℃; for 2h; Autoclave;
98%
With potassium hydroxide In isopropanol at 100℃; Microwave irradiation;
98%
With hydrazine hydrate monohydrate In ethanol at 20℃; for 4h; chemoselective reaction;
98.5%
With hydrogen In o-dimethylbenzene; toluene at 90℃; for 5h; Autoclave; chemoselective reaction;
97%
With potassium fluoride; PMHS In tetrahydrofuran at 20℃; for 0.5h;
96%
With lithium hydroxide monohydrate at 20℃; Inert atmosphere; chemoselective reaction;
96%
With anhydrous silver tetrafluoroborate; 4,4'-Dimethoxy-2,2'-bipyridin; potassium-t-butoxide; hydrogen In 1,4-dioxane at 80℃; for 8h; Autoclave;
1 Example 1
A solution of 16.44 mg (0.04 mmol) 4,4'-dimethoxy-2,2'-bipyridine silver 11.22 mg (0.1 mmol) of potassuim t-butoxide and 1 mL of 1,4-dioxane were charged into an autoclave. After stirring, 165.15 mg (1 mmol) of m-nitroacetophenone was added and the mixture was stirred at 80 °C. The reaction was carried out for 8 hours. After the reaction has finishedm the reaction solution was extracted with water and dichloromethane to collect the organic phase. Then, the organic phase was dried over anhydrous Na2SO4, suction filtered, rotary evaporated and chromatographed to give a yellow solid 3-acetanilide. Yield 96 %.
96.5%
With hydrogen In tetrahydrofuran at 160℃; for 1.5h;
2.4 Typical procedure for the hydrogenation of nitroaromatics
General procedure: The hydrogenation of nitroaromatics was carried out as follows. The mixture of nitroaromatics (1.5mmol), THF (5.0mL) and the AgC/ZrPP-500R catalyst (0.05g) were placed in a 25mL Schlenk flask equipped with a magnetic stirrer and purged five times with N2 to replace the air in the autoclave, five times with pure H2 to replace the N2 prior to experiments. Finally, hydrogen was added to the given pressure and the reactor was heated to 160°C with vigorous stirring. After the hydrogenation reactions, the Schlenk flask was cooled quickly to room temperature. Then the catalyst was filtrated to separate from the solution, the filtrate was added to the volumetric flask and the catalyst was washed with THF and dried at 40°C overnight and used for the next run. The liquid products were analyzed by Shimadzu GC-2014 equipped with an KB-50MS (30m long, 0.32mm i.d., 0.50μm film thickness) and an Agilent 6890/5973 GC-MS system equipped with a HP-5MS column (30m long, 0.25mm i.d., 0.25μm film thickness). The obtained products were isolated and purified by evaporation or column chromatography, and then analyzed by 1H NMR (Fig. S6-S14).
96%
With phenylsilane; triphenylphosphine; sodium iodide In chloroform at 60℃; for 72h; Inert atmosphere; Irradiation;
95%
With palladium 10% on activated carbon; ammsnium formate; mesoporous silica In methanol for 1.5h; Milling;
2. General procedure for the mechanochemical reduction of nitroarenes
General procedure: In a typical experiment, a mixture of nitroarene compound (1.0 mmol),ammonium formate (3.3 mmol, 208 mg, 1.1 equivalent), palladium catalyst (10 % Pdon activated carbon, 2 mol%, 21 mg) and silica (175 mg) was ball milled in thepresence of dry methanol (η = 0.25 μL mg-1) for 90 minutes. After milling, a smallsample (≈ 1 mg) of the crude reaction mixture was suspended in methanol andimmediately analyzed by TLC (typically using dichloromethane : methanol = 20 : 1mixture as an eluent). The crude mixture was left in a well ventilated hood overnight,suspended in methanol and filtered over a Büchner funnel. Evaporation of the filtrateafforded the desired amino-derivative. If necessary, the final product was purified bycolumn chromatography.
95%
Stage #1: 3-Nitroacetophenone In lithium hydroxide monohydrate at 20℃; for 0.0833333h;
Stage #2: With sodium tetrahydridoborate In lithium hydroxide monohydrate at 75℃; for 0.333333h;
2.3.4 Synthesis of amines catalyzed using CoO(at)N-mC
General procedure: To a 10mL round-bottom flask equipped with a magnetic stirrer, CoO(at)N-mC nanocatalyst (30mg), nitroarene (1.0mmol), and H2O (3mL) were added and the reaction mixture was stirred at ambient temperature for 5min, then NaBH4 (3mmol) was added and the resulting mixture heated in an oil bath at 75°C for an appropriate time. After the finishing of the reduction reaction that was followed by applying TLC, CoO(at)N-mC nanocatalyst was separated with the centrifuge, rinsed with ethanol, dried at 60°C to be ready for the next cycle without any purification. After isolation of catalyst, the product was extracted with ethyl acetate and purified by short column chromatography on silica gel, if necessary, to obtain the relevant compound in desired purity.
94%
With hydrogen In isopropanol at 59.84℃; for 1.5h; Autoclave;
94%
Stage #1: 3-Nitroacetophenone With Cu(OH)x impregnated on Fe<SUB>3</SUB>O<SUB>4</SUB> In lithium hydroxide monohydrate for 0.0833333h; Green chemistry;
Stage #2: With sodium tetrahydridoborate In lithium hydroxide monohydrate at 55 - 60℃; for 0.2h; Green chemistry;
A typical procedure for reduction of nitrobenzene to aniline with NaBH4/Nano Fe3O4-Cu(OH)x system
General procedure: In a round-bottom flask (10 mL) equipped with a magnetic stirrer, a mixture of nitrobenzene (0.123 g, 1 mmol) and H2O (3 mL) was prepared. Nano Fe3O4-Cu(OH)x(20 mg, 0.06 mmol, x = 2) was then added, and the resulting mixture was stirred for 5 min. Next, NaBH4 (0.076 g,2 mmol) was added and the reaction mixture was continued to stirring for 3 min at 55-60 °C. TLC monitored the progress of the reaction (eluent, n-hexane/EtOAc: 5/2). After completion of the reaction, the nanocatalyst was separated by an external magnet and the reaction mixture was extracted with EtOAc (2 × 5 mL). Drying organic layer over anhydrous Na2SO4 and then evaporation of the solvent affords the pure liquid aniline in 95 % yield (0.088 g, Table 2, entry 1).
94%
With sodium tetrahydridoborate; ethanol at 20℃; for 0.5h;
The general method for selective reductionof nitroarenes
General procedure: This procedure includes the addition of Fe3O4 Guanidine-CuII (0.6 mol %) to nitro compound (1 mmol) and NaBH4(3 mmol) in ethanol (2 ml) within ambient conditionsand agitated for an appropriate period (Table 1).With the help of TLC, the advancement in reduction isregulated. Later, the catalyst particles were separated usingan external magnet, in addition to washing the mixturewith ethyl acetate (EtOAc) (2 × 5 ml) and H2O(3 × 5 ml).Then anhydrous Na2SO4was used to dehydrate the organiclayer and thus the solvent was evaporated to recover thecrude resultants with reduced pressure. The final step wasperformed by eluting the product with n-hexane: ethylacetate (4:1) solution in column chromatography packed with silica gel.
94%
With sodium tetrahydridoborate; ethanol at 20℃; for 0.5h;
The general method for selective reductionof nitroarenes
General procedure: This procedure includes the addition of Fe3O4 Guanidine-CuII (0.6 mol %) to nitro compound (1 mmol) and NaBH4(3 mmol) in ethanol (2 ml) within ambient conditionsand agitated for an appropriate period (Table 1).With the help of TLC, the advancement in reduction isregulated. Later, the catalyst particles were separated usingan external magnet, in addition to washing the mixturewith ethyl acetate (EtOAc) (2 × 5 ml) and H2O(3 × 5 ml).Then anhydrous Na2SO4was used to dehydrate the organiclayer and thus the solvent was evaporated to recover thecrude resultants with reduced pressure. The final step wasperformed by eluting the product with n-hexane: ethylacetate (4:1) solution in column chromatography packed with silica gel.
93%
With [RuCl(η6-p-cymene)(benzyl N'-thiophene-2-carbonyl-N-(pyridin-2-ylmethyl)carbamimidothioate)]Cl; potassium hydroxide In isopropanol for 10h;
2.3. Procedure for catalytic TH of nitroarenes and carbonylcompounds
General procedure: Substrate (1 mmol) was added to 2-propanol (4 mL) solution ofthe catalyst (0.1 mol %) and KOH (1 mmol), and refluxed at 85 C.The completion of the reaction was checked by TLC. Then, the reactionmixture was cooled to room temperature, eluted throughshort silica gel or alumina bed using 50% hexane-ethyl acetatemixture and analyzed by GC or GC-MS. The products were isolatedfrom the most of the reactions and confirmed by their 1H NMRspectra
92%
With sodium dihydrosulfite; potassium carbonate In lithium hydroxide monohydrate; acetonitrile at 35℃; for 0.5h;
92%
With hydrogen In ethyl acetate at 20℃; for 8h;
92%
With peganine In lithium hydroxide monohydrate at 120℃; for 24h; chemoselective reaction;
92%
With sodium tetrahydridoborate; lithium hydroxide monohydrate In neat (no solvent) at 20℃; for 0.0833333h; Milling;
General procedure: As a representative example, a mixture of nitrobenzene(1 mmol), Ni2BCu2O (54 mg), 1 drop of distilled water, and NaBH4 (2.5mmol) was ground using a simple porcelainmortar and pestle for 1 min at room temperature. After completion of the reaction (checked by TLC), distilled water(5mL) was added to the reaction vessel, and subsequently the reaction mixture transferred to a round-bottom flask (25mL) equipped with a magnetic stirrer. The mixture was stirredvigorously for 2min. Next, the product was extracted with dichloromethane (53mL). The extracts were dried with anhydrous sodium sulfate and then passed through a cottonfilter. Evaporation of the solvent afforded pure aniline in 98%yield.
91%
With sodium dihydrosulfite; potassium carbonate In dichloromethane; lithium hydroxide monohydrate at 35℃; for 5h;
91%
With ammonia hydrochloride; 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate; zinc In lithium hydroxide monohydrate at 20℃; for 8h;
90%
With hydrogen In ethanol at 25℃; for 3h; Sealed tube; Green chemistry;
89%
With potassium fluoride; PMHS; palladium diacetate In tetrahydrofuran; lithium hydroxide monohydrate at 20℃; for 0.5h;
89%
With hydrogen In lithium hydroxide monohydrate at 25℃; for 15h; Green chemistry; chemoselective reaction;
2.3 Procedure for the nitroarene reduction by using Pt-BNP.
General procedure: Nitroarene (0.5 mmol) and Pt-BNP 3 (9.8 mg, 2.5 mol%, 25 wt% of Pt by ICP-OES analysis) were taken in an oven dried reaction tube equipped with magnetic pellet. Water (2.0 mL)was added to the reaction tube and the resulting reaction mixture was stirred at room temperature under hydrogen atmosphere (using H2 balloon) and the reaction was monitored by TLC. After consumption of the starting material, crude product was extracted with ethyl acetate (3 × 20 mL). Then the organic phase was dried over Na2SO4 and concentrated in vacuum. The product was further purified by column chromatography using silica gel to yield pure aniline.
85%
With iron(0); glacial acetic acid In ethanol; lithium hydroxide monohydrate at 30℃; for 1h; sonication;
85%
With hydrogenchloride; iron(0) In ethanol; lithium hydroxide monohydrate for 1.5h; Reflux;
84%
With iron(0); ammonia hydrochloride; glacial acetic acid In ethanol; lithium hydroxide monohydrate Reflux;
84%
With iron(0); ammonia hydrochloride; glacial acetic acid In ethanol; lithium hydroxide monohydrate for 2.16667h; Reflux;
84.6%
With hydrogenchloride; iron(0) In lithium hydroxide monohydrate Reflux;
3.S2 S2. Reduction reaction:
In the reactor,Add 90g (1.6mol) iron powder and dilute hydrochloric acid (37.5% concentrated hydrochloric acid 95g mixed with 265g of water,Dilute hydrochloric acid mass fraction of 9.9%),Into the above solution, 49.5 g (0.3 mol) of 3-nitroacetophenone prepared from S1 was charged under vigorous stirring,Reflux mixing,After sufficient reaction to cool to room temperature,filter,The filtrate was adjusted to neutral with aqueous ammonia,filter,Washed,Dried to give 3-aminoacetophenone 34.3g, a yield of 84.6%The tested melting point of 97-99 ;
82%
With formic acid; tris(2-diphenylphosphinoethyl)phosphine In ethanol at 70℃; for 0.666667h;
81%
In N,N-dimethyl-formamide at 100℃; for 10h;
81%
With 1,3-DIOXOLANE; lithium hydroxide monohydrate; zinc at 70℃; for 11h; Green chemistry; chemoselective reaction;
81%
With anhydrous sodium formate In ethanol at 85℃; for 1h;
80%
With W-7 Raney-Nickel In ethanol for 5h; Heating;
80%
With ethanol; iron(0); calcium(II) chloride In lithium hydroxide monohydrate at 60℃; for 0.5h; chemoselective reaction;
80%
With sodium tetrahydridoborate In lithium hydroxide monohydrate at 75℃; for 0.583333h;
77%
With molybdenum hexacarbonyl; 1,8-diazabicyclo[5.4.0]undec-7-ene In ethanol at 150℃; for 0.25h; microwave irradiation;
74%
With sodium tetrahydridoborate In lithium hydroxide monohydrate at 75℃; for 2.75h; Green chemistry;
2.4. The catalytic activity of PSeCN/Ag in the reduction of nitroarenes
General procedure: Typically, 4-nitroaniline (1 mmol), NaBH4 as reducer (5 mmol), PSeCN/Ag nanocatalyst (20 mg) were added into a 10 mL vial containing 3 mL H2O as the solvent. Then, the reaction mixture was stirred for a certain time at 75 °C. The reaction was checked by TLC. Upon the completion of the reaction, the PSeCN/Ag was isolated by centrifugation and washed with EtOH and H2O to use for another consecutive run. Then, the product was extracted with ethyl acetate and purified by plate or column chromatography.
52%
Stage #1: 3-Nitroacetophenone In tetrahydrofuran at 20℃; for 24h; UV-irradiation;
Stage #2: With aluminum(III) oxide In tetrahydrofuran for 18h; Reflux;
38%
Stage #1: 3-Nitroacetophenone With hydrogen bromide; hypophosphorous acid; glacial acetic acid; sodium iodide In lithium hydroxide monohydrate at 115℃; for 2h; Inert atmosphere;
Stage #2: With sodium hydroxide In lithium hydroxide monohydrate Inert atmosphere;
With palladium(0); benzene Hydrogenation;
With palladium on activated charcoal; ethanol; 2-methoxy-ethanol Hydrogenation;
With palladium on activated charcoal; ethyl acetate Hydrogenation;
With nickel; ethyl acetate Hydrogenation;
With ethanol; platinum Hydrogenation;
With ethanol; nickel at 50℃; Hydrogenation;
With hydrogenchloride; stannous chloride
With ammonium sulfide; ammonia
With sodium dihydrosulfite
With hydrogenchloride; tin
With hydrogenchloride; ethanol; zinc
With iron(0); glacial acetic acid
With ammonium sulfide
With ammonia bei elektrolytischer Reduktion an Nickelkathoden;
With hydrogenchloride; ethanol; stannous chloride
With iron(0); glacial acetic acid
With ethanol; FERROUS SULFATE Reduktion;
With anhydrous copper sulphate; sulfuric acid; copper(II) sulphate bei elektrolytischer Reduktion an Kupferkathoden;
With hydrogenchloride; stannous chloride In ethanol; lithium hydroxide monohydrate at 30℃;
80 %Chromat.
With potassium hydroxide; isopropanol at 100℃; for 0.75h; Microwave irradiation; chemoselective reaction;
84 %Chromat.
With phenylsilane; triphenylphosphine; iron(II) dibromide In toluene at 110℃; for 16h; Inert atmosphere;
Stage #1: 3-Nitroacetophenone With hydrogenchloride; tin In lithium hydroxide monohydrate
Stage #2: With sodium hydroxide In lithium hydroxide monohydrate
95 %Chromat.
With hydrogen at 20℃; for 0.0833333h; Inert atmosphere; Neat (no solvent);
With oxalic acid; titanium(IV) dioxide In lithium hydroxide monohydrate; acetonitrile at 24.84℃; for 1.5h; Inert atmosphere; UV-irradiation;
With hydrogenchloride; dichloro-λ2-stannane dihydrate In methanol; lithium hydroxide monohydrate at 100℃;
9 Example 9
The reduction reaction of meta nitro acetophenone was carried out in a SS316 of 1/8" OD tube of volume 8.5 ml with 1 gm m-nitroacetophenone in 20 ml methanol and 5 gm SnCl2.2H20 in 20 ml 10% HC1 pumped using syringe pumps with a residence Time = 22 min at 100°C. The reaction was seen to be complete with only the product being observed at the outlet.
98 %Chromat.
With cadmium sulphide In isopropanol for 20h; Irradiation; Inert atmosphere;
2.3 Photocatalytic activity
General procedure: The photocatalytic reduction of nitro compounds to their corresponding amines was performed using CdS nanopowder under visible blue LED irradiation. Typically, 20mg of the photocatalyst was added to the 5ml of 1×10-2M nitrocompounds solution in isopropanol. After that, the mixture was sunicated for 5min to obtain a homogeneous dispersion of CdS nanostructure in i-PrOH, then purged argon (5min) and then the vial was sealed up with a rubber stopper. The mixture was stirred magnetically during reaction (20h) and illuminated with a visible blue LED (3W) irradiation. After the reaction, for removing the photocatalyst particles completely, the mixture was centrifuged, and the remaining solution was analyzed with thin layer chromatography (TLC), and by Varian gas chromatograph (CP-3800). Conversion of nitro, yield of amine, and selectivity for amine were defined as follows: where C0 is the initial concentration of nitro compound and Cnitro and Camine are the concentration of the substrate nitro and the corresponding amine respectively, after the photocatalytic reaction.
100 %Chromat.
With titanium dioxide In ethanol for 0.75h; Irradiation; Green chemistry; chemoselective reaction;
Photocatalytic synthesis of aromatic amines
General procedure: Photocatalytic synthesis of aromatic amines. Photocatalytic reactions were carried out in a round bottomed Pyrex flask and irradiated using four high power blue light LEDs 3W lamp or by solar light under magnetic stirring at room temperature. Reaction conditions with solar light: the reduction of the aromatic nitro compounds (0.02 mmol) was carried out in the presence of TiO2-P25 (0.01 g) in EtOH (4 mL) with irradiation for 1-4 h.
96 %Spectr.
With γ-terpinene In ethanol at 80℃; for 2h; Sealed tube; Green chemistry;
With hydrogenchloride; dichloro-λ2-stannane dihydrate In methanol at 100℃; for 0.366667h;
2; 9 Reduction of m-Nitro Acetophenone
Reduction of m-Nitro Acetophenone [0060] Continuous Flow Experiments: [0061] The reaction was carried out in a SS316 of ″ OD tube of volume 8.5 ml with 1 gm m-nitroacetophenone in 20 ml methanol and 5 gm SnCl2.2H2O in 20 ml 10% HCl pumped using syringe pumps with a residence Time=22 min at 100° C. The reaction was seen to be complete with only the product being observed at the outlet.
100 %Chromat.
With oxalic acid; titanium(IV) dioxide; β‐cyclodextrin In lithium hydroxide monohydrate for 1h; Inert atmosphere; Irradiation; Green chemistry;
With oxalic acid; titanium(IV) dioxide In lithium hydroxide monohydrate; acetonitrile at 24.84℃; for 2h; Inert atmosphere; UV-irradiation; Sealed tube; chemoselective reaction;
4.1 General
General procedure: Three kinds of commercial TiO2 samples were used as photocatalyst, i.e., P 25 (Degussa), ST-01 (Ishihara), and MT-150A (Tayca). Bare TiO2 powder (50mg) was suspended in a mixture of acetonitrile (Wako Pure Chemical Industries, Osaka) and water (5cm3) containing NS (50μmol, Sigma-Aldrich Japan, Tokyo) and oxalic acid (200μmol, Wako Pure Chemical Industries, Osaka) in a test tube. The tube was sealed with a rubber septum and then photoirradiated at a wavelength >300nm by a high-pressure mercury arc (Eiko-sha, 400W) under argon (Ar) with magnetic stirring at 298K. After the reaction, the gas phase was analyzed by a gas chromatograph (Shimadzu, GC-8A equipped with MS-5A columns). After the suspension had been filtered to remove the particles, the amounts of NS and product(s) were determined by high-performance liquid chromatography (Jasco, UV-2075Plus detector, PU-2089Plus pump, equipped with an Inertsil ODS-3 column, eluent: aqueous sodium borate buffer/acetonitrile=50:50, flow rate: 0.5cm3min-1 at room temperature) and GC-MS (GC-17A, GCMS-QP5050 (Shimadzu); column: DB-1, 0.25mm, 30m (J&W)).
With hydrogen at 60℃; for 4h; Ionic liquid; chemoselective reaction;
With β-D-glucopyranose; lithium hydroxide monohydrate at 25℃; for 12h; UV-irradiation;
93 %Chromat.
With hydrogen; triethylamine In tetrahydrofuran; lithium hydroxide monohydrate at 110℃; for 8h;
With glacial acetic acid; zinc In lithium hydroxide monohydrate at 20℃;
General procedure
General procedure: A mixture of nitrobenzenes 1 (1mmol) and Zn (215mg, 3.3mmol) in solvent of HOAc-H2O (2.5mL, v/v=2:3) in a flask was stirred at room temperature until the starting nitrobenzenes were consumed completely (monitored by TLC analysis). NaNO2 (1.1mmol) saturated solution was added dropwise at 0-5°C in an ice-water bath followed by adding a 1.5mmol of NaN3 saturated solution. Then the ice-water bath was removed and the reaction proceeded at room temperature. After 2h, terminal alkynes 2 (1.2mmol), CuI (0.05mmol) and DMSO (1.5mL) were added to the above system at room temperature. After 5h, the mixture was treated with H2O (15mL) and extracted with EtOAc (3×15mL) and the combined organic layer was washed with brine (3×5mL), dried over Na2SO4 and concentrated under reduced pressure to afford a crude product. Purification by column chromatography on silica gel afforded the desired 1,4-disubstitued 1,2,3-triazol 3.
With ammsnium formate In lithium hydroxide monohydrate at 90℃; for 15h; Inert atmosphere; Green chemistry; chemoselective reaction;
99 %Chromat.
With cadmium sulphide In isopropanol for 0.75h; Inert atmosphere; Sonication; Irradiation;
Experimental
General procedure: As optimized reaction conditions, a solution of nitroaromaticcompounds (0.01 M) in an appropriatesolvent and 20 mg of CdS-NP were sonicated andslowly purged with N2 for 5 min. Then, the reactionvessel was sealed up with a rubber stopper and themixture was stirred magnetically and irradiated with blue LED (4 × 1 W, λ ≥ 420 nm, intensity: 80 lumen)or sunlight (of daily ambient temperature andsunlight intensity range of 80-100 × 103 lux).The reaction conversion was monitored by thinlayer chromatography (TLC). After completing thereaction, the mixture was centrifuged and supernatantwas removed and analyzed on a GC Alientgas chromatograph (Nonpolar CP-Sil 8 column (30m × 0.32 mm), Varian Chrompack (Middelburg, TheNetherlands).
With hydrogen In neat (no solvent) at 85℃; for 1.5h; Green chemistry;
100 %Chromat.
With hydrazine hydrate monohydrate at 85℃; for 6h; chemoselective reaction;
86 %Chromat.
With borane-ammonia complex In methanol; lithium hydroxide monohydrate at 20℃; for 2h; Sonication; chemoselective reaction;
86 %Chromat.
With formic acid In lithium hydroxide monohydrate; isopropanol at 20℃; for 3h; Irradiation; chemoselective reaction;
77 %Chromat.
With C18H13Cl2N3ORu; sodium isopropanolate; isopropanol at 110℃; for 5h; Inert atmosphere; Schlenk technique; chemoselective reaction;
With formic acid; ammsnium formate In methanol at 25℃; for 1h;
> 99 %Chromat.
With borane-ammonia complex In methanol; lithium hydroxide monohydrate at 25℃; for 0.0833333h;
89 %Chromat.
With hydrogen In ethanol; lithium hydroxide monohydrate at 110℃; for 16h; Autoclave;
2.4 General methods for catalytic reactions in the autoclave
General procedure: In an 8mL glass vial fitted with a magnetic stirring bar and a septum cap, the catalyst (the amount depends on the catalyst) was added followed by the nitroarene (0.5mmol), the internal standard (hexadecane, 20mg) and the solvent (2mL). A needle was inserted in the septum cap, which allows dihydrogen to enter. The vials (up to 7) were placed into a 300mL steel Parr autoclave which was flushed twice with dihydrogen at 20bar and then pressurized to 50bar. Then the autoclave was placed into an aluminum block pre-heated at 110°C. At the end of the reaction, the autoclave was quickly cooled down at room temperature with an ice bath and vented. Finally, the samples were removed from the autoclave, diluted with a suitable solvent, filtered using a Pasteur pipette filled with Celite (6cm pad) and analyzed by GC using n-hexadecane as an internal standard. Control experiments showed that the position of the vial inside the autoclave is not influential. The same outcome was obtained when the reaction was repeated by moving a vial from a peripheral to a central position.
96 %Chromat.
With sodium tetrahydridoborate In ethanol; lithium hydroxide monohydrate at 20℃; for 4h; Inert atmosphere;
With formic acid In lithium hydroxide monohydrate at 25℃; for 0.75h;
With hydrogen In tetrahydrofuran; lithium hydroxide monohydrate at 120℃; for 2h; chemoselective reaction;
With formic acid; ammsnium formate In ethanol; lithium hydroxide monohydrate at 25℃; for 0.6h; chemoselective reaction;
100 %Chromat.
With cadmium sulfide loaded on silica-coated Fe3O4 nanoparticles In isopropanol for 20h; Irradiation; Inert atmosphere;
2.3 Photocatalytic activity
General procedure: The Fe3O4/SiO2/CdS (S2) with average amount of CdS has been chosen as a photocatalyst for the photocatalytic reduction of nitro compounds under the blue LED irradiation. In a 10mL flask, 5ml of 0.01M nitro compounds solution and 0.02g photocatalyst were charged. Then the flask was charged with pure argon. The resulting mixture was stirred for 20h under LED irradiation. After this time, the catalyst was simply separated by employing an external magnetic field and the remaining solution was analyzed using thin-layered chromatography (TLC) and Varian gas chromatograph (CP-3800). The conversion of nitro substrate, yield of amine, and selectivity for amine were defined as follows: Conversion (%) = (C0-Cnitro)/C0×100 Yield (%) = Camine/C0×100 Selectivity (%) =Camine/(C0-Cnitro)×100Where C0 is the initial concentration of nitro compound and Cnitro and Camine are the concentration of the nitro substrate and the corresponding amine respectively, after the photocatalytic reaction.
99 %Spectr.
With C22H25Cl2N3ORuS2; potassium hydroxide In isopropanol at 82℃; for 12h; chemoselective reaction;
2.4 Transfer hydrogenation of carbonyl/nitro compounds
General procedure: Catalyst (0.1mol %) and KOH (1mmol) were dissolved in 2-propanol (4mL). To this solution, substrate (1mmol) was added and the mixture was refluxed (82°C). The progress of the reaction was monitored by GC at regular intervals. After the completion of the reaction, the reaction mixture was cooled to room temperature and filtered through silica gel or alumina bed, and eluted using 50% ethyl acetate-hexane mixture. The eluted solution was reduced and analyzed by GC and/or GCMS.
With hydrogen In ethanol at 20℃; for 2h; chemoselective reaction;
Catalytic Experiment
General procedure: In this work, the following of nitroaromatic compoundswere used:The liquid-phase hydrogenation reaction of nitroaromaticcompounds can be presented as:It was carried out at room temperature under an atmosphericpressure of H2. A sample of the catalyst(50 mg) was placed in a round-bottomed threeneckedflask and the system was purged with hydrogenfor 30 min. A solution of the substrate in ethanol 0.2 M(or in tetrahydrofuran in the case of using o- andp-dinitrobenzene as a substrate) was then poured intothe reactor by means of a feed cock of the reactionmixture. The concentration of platinum in the reactionmixture was 0.85 mol %. The reaction was carriedout with vigorous stirring on a magnetic stirrer at a rateof 900 rpm in the monitoring mode by means of gasliquidchromatography until the peak of the startingcompound disappeared on the chromatogram. At theend of the experiment, the stirring was stopped; thecatalyst was separated from the reaction mixture bycentrifugation.Analysis of the reaction products was performedusing GC with a Chromatek Crystal 5000.2 chromatographwith a flame ionization detector (FID) and acapillary column CR-5 (2 mm × 25 m) at a temperatureof 190°C. The peaks were identified on the basis of the experimentally obtained retention times of individualcompounds (nitrobenzene, o-dinitrobenzene,p-dinitrobenzene, p-hydroxynitrobenzene, p-nitroacetophenone,nitrocyclohexane, aniline, o-phenylenediamine,p-phenylenediamine, p-hydroxyaniline,p-nitrophenylethanol, aminocyclohexane). Thestructure and purity of the products obtained wereconfirmed by NMR spectroscopy. The 1H and 13CNMR spectra were recorded on a Bruker Avance 300spectrometer in solvents CDCl3 and DMSO-d6.
With hydrogen In toluene at 30℃; Autoclave;
2.5. Catalytic hydrogenation of nitroarenes
General procedure: The liquid-phase hydrogenation reaction of nitroarenes wasperformed in a magnetically stirred 50 mL stainless steel autoclave.A quantity of catalyst (50 mg) was added to the autoclavecontaining nitroarene (1 mmol) and toluene (15 mL). Then, theautoclave was flushed with 10 bar hydrogen five times. Afterbeing sealed, the autoclave was charged with H2 until 5 bar andthen it was kept at 30 °C. A rotation rate of 1000 r/min was used in this work, which can effectively exclude the influence ofmass transfer on the reactions. The reactants and productswere analyzed with a gas chromatograph (GC-112A, FID detector)equipped with an HP-5 column (30 m). In the recyclingexperiments, the solid catalyst was separated by simple decantationand directly used for the next cycle without any further treatment.
With aluminum (III) chloride; bromine; In diethyl ether; at 0 - 20℃; for 1h;
2-bromo-1-(3-nitrophenyl)ethanone (2a-1). To a suspension of commercially available 3- nitroacetophenone (4.82 g, 29.19 mmol) in anhydrous diethyl ether (25 mL) was added aluminum chloride (0.16 g, 1.20 mmol). The reaction mixture was then cooled to 0C before dropwise addition of bromine (1.50 mL, 29.19 mmol). The reaction was stirred for lh at room temperature until complete conversion of the starting material (1H NMR monitoring) and quenched quickly to avoid di-brominated compound formation. After addition of water (30 mL), the mixture was extracted with diethyl ether (3 x 30 mL) and dried with MgSO4 to afford compound 2a-1 as a yellowish brown solid (5.73 g, 97% yield). 1H NMR (CDCl3, 200 MHz): delta 4.50 (s, 2H, H1), 7.73 (t, J = 8.0 Hz, 1H and H7), 8.31 (ddd, J = 7.8, 1.7, 1.1 Hz, 1H, H8), 8.43 (ddd, J = 8.2, 2.3, 1.1 Hz, 1H, H6), 8.76 (t, J = 1.9 Hz, 1H, H4). 13C NMR (CDCl3, 200 MHz): delta 30.4, 123.9, 128.2, 130.4, 134.6, 135.2, 148.6, 189.5. MS-ESI (m/z): [M+H]+= 244.9.
97%
With aluminum (III) chloride; bromine; In diethyl ether; at 0 - 20℃; for 1h;
To a suspension of commercially available 3-nitroacetophenone (4.82 g, 29.19 mmol) in anhydrous diethyl ether (25 mL) was added aluminum chloride (0.16 g, 1.20 mmol). The reaction mixture was then cooled to 0C before dropwise addition of bromine (1.50 mL, 29.19 mmol). The reaction was stirred for 1h at room temperature until complete conversion of the starting material (1H NMR monitoring) and quenched quickly to avoid di-brominated compound formation. After addition of water (30 mL), the mixture was extracted with diethyl ether (3 x 30 mL) and dried with MgSO4 to afford compound 2 as a yellowish brown solid (5.73 g, 97% yield). 1H NMR (CDCl3, 200 MHz): delta 4.50 (s, 2H, H1), 7.73 (t, J = 8.0 Hz, 1H and H7), 8.31 (ddd, J = 7.8, 1.7, 1.1 Hz, 1H, H8), 8.43 (ddd, J = 8.2, 2.3, 1.1 Hz, 1H, H6), 8.76 (t, J = 1.9 Hz, 1H, H4). 13C NMR (CDCl3, 200 MHz): delta 30.4, 123.9, 128.2, 130.4, 134.6, 135.2, 148.6, 189.5. MS-ESI (m/z): [M+H]+= 244.9.
91%
With N-Bromosuccinimide; tetrachlorosilane; In acetonitrile; at 20℃; for 7h;
General procedure: To a mixture of NXS and substrate (1 or 6) in CH3CN at room temperature was added SiCl4 and the mixture left to stir until TLC showed the disappearance of the starting material. The reaction was then poured onto H2O and the mixture extracted with CH2Cl2. The extracts were combined, dried over MgSO4 and evaporated. The residue was purified by recrystallization (pet. ether-Et2O, 3:1) to give pure 2b-2g, 3b, or by silica gel column chromatography (hexane-EtOAc 10:1 or 30:1) to give pure 2a,h,i, 3a-5 or 7-9, respectively
89%
With pol(vinylphenyltrimethylammoniumtribromide) resin; In methanol; water; at 65℃; for 1h;
General procedure: A mixture of 2.5 mmol of substrate, 4.5 mL methanol, and 0.5 mL of water was stirred for 5 min, and then 1 g of PVBMATB resin was added, and the mixture was stirred 1 h at 65 C. Afterward, the resin of poly(vinylbenzyltrimethylammonium bromide) was recycled through filtration and washed with ether. The combined organic layer was washed twice by water (20 mL), and dried over anhydrous Na2SO4. After filtration, the solvent was removed under reduced pressure, and the residual was treated with silica gel column chromatography(Petroleum ether/AcOEt = 20/1,v/v) to generate the product.
84%
With pyridinium hydrobromide perbromide; acetic acid; at 20℃; for 1h;Inert atmosphere;
Synthesis 53; 2-Bromo-1-(3-nitrophenyl)ethanone/77-Nitroacetophenone (20 g) was dissolved in acetic acid (150 mL) under argon. Pyridinium tribromide (38.7 g) was added at once; the reaction was allowed to stir at room temperature for 1 hour and then quenched with water (250 mL). The product was filtered and air dried to give the title compound (25 g, 84%).
78%
With hydrogen bromide; potassium iodide; sodium nitrite; In water; acetonitrile; at 0 - 20℃; for 12h;
General procedure: In a RBF cooled in ice bath at 0 C, HBr(12 mmol, in 2 ml of water) was taken. To this a solution of NaNO2(5 mmol, in 5ml of water) was added drop wise. The reaction was stirred for 15min maintaining the temperature at 0 C and KI (5 mol %) was added. After 10 min ketone(10 mmol) was added at once. After 15 min reaction temperature was brought to room temperature slowly. Reaction was monitored by TLC (ethyl acetate: pet ether, 1:9). After completion of reaction 50 ml of CHCl3 was added and organic layer separated. Aqueous layer was extracted with 25 ml of CHCl3 and combined organic layer was washed with 10% NaHSO3 solution (2 x 20 ml) and 10% NaHCO3 solution (2 x 20 ml).The organic layer was dried over sodium sulphate and concentrated under reduced pressure. Pure product was obtained after column chromatography (silica gel, 60-120, eluentethyl acetate: pet ether).
75%
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 60℃; for 3h;
N-bromosuccinamide (1.3 g, 7.2 mmol, 1.2 Eq) was added portionwise to a solution of compound 5 (1 g, 6 mmol, 1 Eq) in anhydrous DMF(5 ml) at rt. The reaction mixture was stirred at 60 C for 3 h. Thereaction mixture was cooled and extracted between EtOAc (40 ml) and water (60 ml). The organic layer was washed with water (3 × 50 ml).The organic layer was dried over anhydrous Na2SO4 and evaporated under vacuum. The crude residue was purified through column chromatography(hexane, EtOAc; 100, 1) to give the titled product 6. Yield: 75%. m.p.: 95-6 C. 1H NMR (400 MHz, DMSO-d6) delta 8.71 (t,J = 2.0 Hz, 1H, Ar-H), 8.51-8.48 (m, 1H, Ar-H), 8.44-8.41 (m, 1H, Ar-H), 7.87 (t, J = 8.0 Hz, 1H, Ar-H), 5.06 (s, 1H, CH2Br). 13C NMR(100 MHz, DMSO-d6) delta 190.75 (Ar-C), 148.46 (Ar-C), 135.67 (Ar-C),135.33 (Ar-C), 131.13 (Ar-C), 128.37 (Ar-C), 123.46 (Ar-C), 34.61(CH2Br). LC/MS: 245 (M + 1)+.
73%
With bromine; In acetic acid; at 55℃; for 0.5h;
48mmol of m-nitroacetophenone was dissolved in 300mL of glacial acetic acid and warmed to 55C. 48mmol of bromine was then added drop-to-drop allowing the discoloration of the solution before add next drop. After 30min at 55C, 101g of crushed ice was added to the reaction and the formed precipitated filtered out, washed with water and recrystallized from ethanol/petroleum ether, rendering the compound 2-brome-1-(m-nitrophenyl)ethan-1-one. Yield: 73%.
70%
With phenyltrimethylammonium tribromide; In tetrahydrofuran; at 20℃; for 1h;
A solution of phenyltrimethylammonium tribromide (50.1 g, 133 mmol) in THF (200 mL)was added dropwise to a stirred solution of 1-(3-nitrophenyl)ethanone (20 g, 121 mmol)in THF (200 mL) at room temperature. The reaction mixture was allowed to stir at roomtemperature for lh. The white suspension was filtered and the filter cake was washed withTHF, the filtrate was evaporated in vacuum to give a yellow oil. The residue was then dissolved in EtOAc and was washed with water. The organic layer was dried (MgSO4) and evaporated in vacuum to give a yellow oil that solidified into an yelLow solid. Solid recrystallised from propan-2-ol and final product was isolated as an off-white solid. 2-Bromo-l-(3-nitrophenyl)ethanone (20.5 g, 70 % yield).(?H, 600 MHz, 20C, CDC13) 8: 8,83 (IH, t, 3 = 2Hz), 8.49 (IH, ddd, I = 1.0, 2.3, 8.2Hz), 8.34 (1H, ddd, I = 1.0, 1.7, 7.8 Hz), 7.75 (1H, t, J = 8.1 Hz), 4.49 (2H, s).(?3C, 150 MHz, 20C, CDC13) 8: 189.3, 148.5, 135.1, 134.4, 130.2, 128.1, 123.8, 29.9Melting point (mp): 90-9 1 DC.
70%
With phenyltrimethylammonium tribromide; In tetrahydrofuran; at 20 - 25℃; for 1h;
A solution of phenyltrimethylammonium tribromide (50.1 g, 133 mmol) in THF (200 mL) was added dropwise to a stirred solution of l-(3-nitrophenyl)ethanone (20 g, 121 mmol) in THF (200 mL) at room temperature. The reaction mixture was allowed to stir at room temperature for lh. The white suspension was filtered and the filter cake was washed with THF, the filtrate was evaporated in vacuum to give a yellow oil. The residue was then dissolved in EtOAc and was washed with water. The organic layer was dried (MgS04) and evaporated in vacuum to give a yellow oil that solidified into a yellow solid. Solid recrystallised from isopropandl and final product was isolated as an off-white solid. 2-Bromo-l-(3-nitrophenyl)ethanone (20.5 g, 70 % yield). (1H, 600 MHz, 20C, CDC13) deltaEta: 8.83 (1H, t, J = 2Hz), 8.49 (1H, ddd, J = 1.0, 2.3, 8.2 Hz), 8.34 (1H, ddd, J = 1.0, 1.7, 7.8 Hz), 7.75 (1H, t, J = 8.1 Hz), 4.49 (2H, s). (13C, 150 MHz, 20C, CDC13) 6C: 189.3, 148.5, 135.1, 134.4, 130.2, 128.1, 123.8, 29.9. Melting point (mp): 90-91 C.
34%
With bromine; In acetic acid; at 60℃; for 2h;
Into a 500-mL 3-necked round-bottom flask, was placed a solution of l-(3-mtrophenyl)ethanone (50 g, 303 03 mmol, 1 00 eqmv) in acetic acid (300 mL), Br2 (53 5 g, 331 6 mmol, 1 00 equiv) The resulting solution was stirred for 2 h at 6O0C in an oil bath The reaction was then quenched by the addition of ice and the solids were collected by filtration The crude product was re-crystallized from ethyl acetate/petroleum ether in the ratio of 1 10 This resulted in 25 g (34%) of 2-bromo-l-(3-mtrophenyl)ethanone as a white solid.
With bromine; In chloroform;
Step A 60 g. of 3-nitroacetophenone in 250 ml. of chloroform is treated with 58.2 g. of bromine in 50 ml. of chloroform. The solvent is evaporated and the product separated by filtration and recrystallized from benzene to provide alpha-bromo-3-nitroacetophenone, m.p. 91-94 C.
With bromine; In diethyl ether; at -5 - 20℃;
Example 6; Preparation of l-[(lalpha,5alpha,6alpha)-3-(2,4-difluorophenyl)-3-azabicyclo[3.1.0]hex-6-yl]-3-[3-(2- methyl-l,3-thiazol-4-yl)phenyl]urea:Step L- 2-bromo-l-(3-nitrophenyl)ethanone:To a stirred solution of 3-nitro acetophenone (0.0121 mole) in diethyl ether at -5 to 00C, bromine (0.0242 mole) is added at the same temperature and the reaction mixture is stirred at room temperature for 10 hours. The reaction mixture is then filtered, washed with diethyl ether followed by pet. ether (cold) and dried under vacuum. 1H NMR (CDCI3): delta 4.48 (s, 2H); 7.69 (m, IH); 8.31 (dd, IH); 8.45 (dd, IH); 8.79 (s, IH).
With aluminum (III) chloride; bromine; In diethyl ether; at 0 - 20℃;
General procedure: Equimolar quantities of substituted acetophenones and bromine, dissolved in dry ether with a catalytic amount of AlCl3, were stirred for 1 hr at 0C and then allowed to warm at room temperature until the disappearance of HBr. The white solid was isolated by filtration and washed with petroleum ether to give pure product in good yield (76-80%).
With N-Bromosuccinimide; In diethyl ether; at 20℃;Irradiation; Inert atmosphere;
General procedure: General procedure for the synthesis of alpha-bromoacetophenones (2a-g): Acetophenone 1a (1.0 g, 8.3 mmol) was dissolved in 20 mL diethyl ether in a two neck round bottom flask and recrystallised NBS (2.9 g, 16.8 mmol) was added portion wise. The reaction was irradiated using Philips HPL-N (250 W, lambda = 200-600 nm) lamp fitted with a water circulation arrangement at room temperature under nitrogen atmosphere. After completion of the reaction, the reaction mixture was filtered, diluted with ether and washed with water. The organic layer was separated, dried with Na2SO4 and the solvent was removed under vacuum to yield alpha-bromoacetophenone (2a). Similar procedure was followed for the synthesis of substituted alpha-bromoacetophenones (2b-g).
2.2. Synthesis of indole chalcone derivatives
General procedure: In an RB flask, 1H-indole-3-carboxaldehyde (1 mmol) andappropriate acetophenones (1.2 mmol) were taken and 5 ml ofethanol and 5 drops of piperidine were added. The resulting solutionwas then refluxed at 70 °C and TLC was used to track the reactionprogress. Upon accomplishement of the reaction, thereaction mixture was transferred into cold water and furtherneutralized utilizing 1 N hydrochloric acid. The crude precipitateformed was filtered out, dried and recrystallized from chloroform.All the indole chalcones (1 to 25) were characterized using spectraltechniques and the spectral data are listed in the supplementarydata.
With ammonium acetate; sodium cyanoborohydride; In methanol; at 27℃; for 24h;Molecular sieve;
To a stirred solution of compound 1-(3-nitrophenyl)ethan-1-one 63 (5.Og,30.27 mmol) in MeOH (100 mL) was added molecular sieves & ammonium acetate (23.33 g, 302.7 mmol), charged sodium cyano borohydride (1 .38 g, 21.19 mmol) portion wise, reaction mixture was stirred at room temperature for 24 h, reaction was monitored by TLC. Solid obtained was filtered out & filtrate was concentrated to get crude. Crude was diluted with 10% IPA in DCM & organic layer was extracted at alkaline pH, organic layer was concentrated to obtain 1-(3-nitrophenyl) ethan-1-amine as colorless liquid (2.10 g, 42% yield). ‘HNMR (400 MHz, DMSO-d6): ö 8.27 (s, 1H), 8.06 (d, 1H), 7.82 (d, 1H), 7.61-7.57 (m, 1H), 4.15-4.10 (m, 1H), 2.05 (br s, 1H), 1.27-1.26 (m, 3H) MS: 167.00 (M+H).
> 99%Spectr.
With [pentamethylcyclopentadienyl*Ir(N-phenyl-2-pyridinecarboxamidate)Cl]; ammonium formate; In d(4)-methanol; at 37℃; for 15h;
General procedure: A carbonyl compound (0.2 mmol), 1,3,5-trimethoxybenzene (0.1 mmol, internal standard) andIr1 (2 μmol, 1 mol%) were added to a 1.5-dram vial equipped with a magnetic stir bar inCD3OD (0.5 mL). Solid HCOONH4 (2 mmol, 10 equiv.) was added to the vial and the solutionwas stirred at 37 C for 15 h. The crude reaction mixture was analyzed by 1H NMR spectroscopyusing 1,3,5-trimethoxybenzene as an internal standard (IS) for peak integrations. Each reactionwas performed in triplicate and the average yield was calculated.
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium tert-butylate; copper(I) triflate; 5-[(2S)-pyrrolidine-2-yl]-1H-tetrazole; In N,N-dimethyl-formamide; at 25℃; for 1.5h;Catalytic behavior;
General procedure: A round-bottom flask was charged with alcohol (2 mmol), CuOTf (0.1 mmol, 0.05 equiv) (S)-5-(pyrrolidin-2-yl)-1H-tetrazole (0.1 mmol, 0.05 equiv), TEMPO (0.1 mmol, 0.05 equiv), t-BuOK (2 mmol, 1 equiv) and DMF (5 ml). The reaction mixture was stirred at 25 C open to air until the completion of the reaction, as monitored by TLC. The mixture was then diluted with CH2Cl2 (20 ml), washed with water, dried over Na2SO4, and evaporated under vacuum to give the crude product, which was purified by column chromatography to give the pure product.
95%
With dihydrogen peroxide; acetic acid; sodium bromide; In water; at 60℃; for 2h;Inert atmosphere;
General procedure: Under nitrogen atmosphere, to a solution of substrate alcohol (0.5 mmol) in aceticacid (1.0 mL) was added a stock-solution of aqueous NaBr solution (1.94 M, 25 muL)and 30% aqueous H2O2 (50 muL, 0.5 mmol). After stirring the mixture for one hour at60 C, additional 30% aqueous H2O2 (50 muL, 0.5 mmol) was added, and stirring wascontinued for another one hour. After cooling, the mixture was poured into a saturatedaqueous NaHCO3 solution (ca. 30 mL) with the aid of CH2Cl2, and resulting mixturewas extracted with CH2Cl2. The combined organic layers were dried over anhydrousMgSO4, filtered and concentrated in vacuo. The residue was chromatographed onsilica gel (flash column or preparative TLC) to afford the corresponding ketone.
90%
With 1-methyl-1H-imidazole; [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrakis(acetonitrile)copper(I) trifluoromethanesulfonate; sodium chloride; In neat (no solvent);Milling; Green chemistry;
General procedure: 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO, 9.4 mg,0.06 mmol, 3 mol %), 2,2?-bipyridyl (9,4 mg, 0.06 mmol,3 mol %), [Cu(CN)4]OTf (22.6 mg, 0.06 mmol, 3 mol %) and1-methylimidazole (NMI, 11.5 mg, 11.2 muL, 0.14 mmol,7 mol %) were placed in a zirconia-milling beaker (45 mL)equipped with four balls (two balls × 5 mm , two balls ×12 mm ) of the same material. The jar was sealed and ballmilled for 1 min. Then, benzyl alcohol (216.3 mg, 207 muL,2.0 mmol), NaCl (1.0 g) together with other two zirconia balls(12 mm ) were added and the reaction mixture was subjectedto grinding for further 10 minutes overall (two cycles of5 minutes each). The first milling cycle was followed by a breakof 2 min leaving in the meantime the uncovered jar in open air.The progress of the reaction was monitored by TLC analysis(heptane/AcOEt 9:1 v/v) and GC-MS analysis on an aliquot ofthe crude. Upon completion of the ball milling process, the jarwas opened, the milling balls were removed and the resultingcrude product (adsorbed on NaCl) was then easily transferredinto a separating funnel filled with an aqueous 10% citric acidsolution (20 mL). The aqueous phase was extracted withcyclopentyl methyl ether (or alternatively with AcOEt)(3 × 15 mL). The combined organic fractions were washed withH2O (25 mL) and brine (25 mL), then dried over Na2SO4, andconcentrated in vacuo to give benzaldehyde in high yield (195 mg, 92%) and good purity (>93% by GC analysis). Alternatively, after completion of the reaction, the resulting crudeproduct (adsorbed on NaCl) can be also easily purified by ashort column chromatography on silica gel using heptane/ethylacetate (9:1 v/v) as the eluents to afford pure aldehyde 2b inhigh yield (202 mg, 95%) as a colourless liquid.
87%
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; at 75℃; for 1.66667h;
General procedure: A mixture of alcohols (1 mmol) and DBDMH or DCDMH (1-1.5 mmol) in a 10 mL round-bottomed flask sealed with a stopper, was stirred in an oil-bath for the appropriate time and temperature (Table 1) under solvent-free condition. Then, as monitored by TLC (eluent n-hexane/acetone 10:2), hot water (10 mL) was added to mixture and stirred magnetically for 10 min. Then, the solution was extracted with (CH2Cl2/water (2 × 10 mL)) and organic phase dried over anhydrous Na2SO4 (1 g). Evaporation of the solvent gave the corresponding carbonyl compounds. Melting points and spectral data of all products are fully consistent with those previously reported. The structures of the products were confirmed from physical and spectroscopic data such as melting points, 1H NMR and 13C NMR spectra, fully consistent with those previously reported.17,18
70%
With 1-hydroxy-1H-1,2,3-benziodoxathiole 1,3,3-trioxide; Oxone; cetyltrimethylammonim bromide; In water; at 20℃; for 2h;Green chemistry;
General procedure: The alcohol (2 mmol) was added to a solution of IBS (0.02 mmol, 0.01 eq), oxone (2.2 mmol, 1.1 equiv.) and 3 wt% CTAB solution (5 mL). The mixture was stirred at room temperature. The reaction was monitored by TLC. After completion, the solution was extracted with CH2Cl2 (3 × 10 mL). The combined organic phase was then filtered through a pad of silica gel and evaporated under vacuum to afford the desired product.
62%
With tert.-butylhydroperoxide; eosin y; In decane; acetonitrile; at 25℃; for 72h;Inert atmosphere; Irradiation; Molecular sieve; Green chemistry;
General procedure: Oven dried round bottom flask was charged with Eosin Y (5 mmol) alcohol (1 mmol) and 3 equiv. of TBHP (5.5 M in decane) in dry ACN. The resulting mixture was degassed for 15 mins, followed by back filling N2, and then irradiated under Blue LED light (12W, 455 nm) at room temperature (25 oC). After reaction completion monitored through TLC, the mixture was diluted with 15 ml of 10% NaHCO3 solution, and extracted with EtOAc (3 × 20 ml). The combined organic extracts were washed with brine (20 ml), dried over Na2SO4, and concentrated on vacuo. Purification of the crude product on silica gel using EtOAc:Hexane as solvent system afforded the desired product.
With tert.-butylhydroperoxide; copper(l) iodide; oxygen; In neat (no solvent); at 50℃; for 4h;
General procedure: The 1-arylethanol (1 mmol) was added to a mixture of CuI (30 mol%) and TBHP (5-6 M in decane, 2 equiv) in a reaction tube at r.t. under an O2 atm (O2 balloon). The resulting mixture was stirred at 50 C for 3- 8 h (TLC monitoring).
3.1. Synthesis of Cinnamylideneacetophenones
General procedure: All starting reagents were purchased from Sigma-Aldrich. Compounds were synthesizedby Claisen-Schmidt condensation, according to the method reported by Weldon and co-authors,with minor modifications [20-22]. Cinnamaldehyde (6 mmol) was added to solution of respectiveacetophenone (5 mmol) in ethanol (5 mL). The solution was stirred at room temperature for 30 min,followed by dropwise addition of 5 mL ethanolic solution of NaOH (1.0 M). The progress of reactionwas checked by thin-layer chromatography (TLC) analyses. Reaction medium was poured intocrushed ice. Precipitated crude products were filtered, washed with cold water, and dried at roomtemperature. Soluble crude products were partitioned with ethyl acetate (3 25 mL). Organic phasewas concentrated under reduced pressure. Compounds 2, 7, 8 and 10-7 were recrystallized in ethanol.Compounds 3-6, 9 and 18 were recrystallized in mixtures of hexane and chloroform.
79%
With sodium hydroxide In ethanol; water at 20℃;
With titanium tetrachloride In tetrahydrofuran at -60 - 0℃;
In 5,5-dimethyl-1,3-cyclohexadiene; at 140.0℃; for 12.0h;
In a 250 mL round bottom flask was added 16.5 g (100 mmol) of 3-nitroacetophenone, 26.5 mL of N,N-dimethylformamide dimethyl acetal (200 mmol) and 100 mL of xylene. The mixture was heated to 140C for 12 hours. Then the reaction mixture was cooled to room temperature and the formed precipitate was filtered off, washed with petroleum ether and diethyl ether followed by purification by chromatography using ethyl acetate/cyclohexene (25/75) to afford 19.6 g of a yellow solid. Yield: 89%. 1H NMR (200 MHz, DMSO-d6) delta 8.59 (t, 1H), 8.42 - 8.23 (m, 1H), 7.81 (d, J = 12.1 Hz, 1H), 7.70 (t, J = 7.9 Hz, 1H), 5.89 (d, J = 12.1 Hz, 1H), 3.17 (s, 1H), 2.95 (s, 1H). 13C NMR (50 MHz, DMSO-d6) delta 182.8, 155.2, 147.9, 141.6, 133.4, 129.8, 125.1, 121.5, 90.3, 44.7, 37.3.
79%
Heating / reflux; Neat (no solvent);
3-Nitroacetophenone (5.0 g, 30.3 mmol) in dimethylformamide-dimethylacetal (10 mL) is heated at reflux overnight. The reaction mixture is cooled to room temperature and evaporated to remove the volatiles. The residue is slurried in ethyl ether and the suspension is filtered and washed with ether to give 10.5 g (79%) of 3-(dimethylamino)-1-(3-nitrophenyl)-2-propen-1-one, 104-105 C.
79%
Heating / reflux;
3-Nitroacetophenone (5.0g, 30.3 mmol) in dimethylformamide-dimethylacetal (10 mL) was heated at reflux overnight. The reaction mixture was cooled to room temperature and evaporated to remove the volatiles. The residue was slurried in ethyl ether and the suspension was filtered and washed with ether to give 10.5 g (79%) of 3-(dimethylamino)-1-(3-nitrophenyl)-2-propen-1-one, 104-105 C.
79%
Heating / reflux;
3-Nitroacetophenone (5.0g, 30.3 mmol) in dimethylformamide-dimethylacetal (10 mL) was heated at reflux overnight. The reaction mixture was cooled to room temperature and evaporated to remove the volatiles. The residue was slurried in ethyl ether and the suspension was filtered and washed with ether to give 10.5 g (79%) of 3-(dimethylamino)-1-(3-nitrophenyl)-2-propen-1-one, 104-105 C.
79%
Heating / reflux;
Step 1: 3-(Dimethylamino)-1-(3-nitrophenyl)-2-propen-1-one 3-Nitroacetophenone (5.0 g, 30.3 mmol) in dimethylformamide-dimethylacetal (10 mL) is heated at reflux overnight. The reaction mixture is cooled to room temperature and evaporated to remove the volatiles. The residue is slurried in ethyl ether and the suspension is filtered and washed with ether to give 10.5 g (79%) of 3-(dimethylamino)-1-(3-nitrophenyl)-2-propen-1-one, 104-105 C.
With N-ethyl-N,N-diisopropylamine; In toluene; for 4.0h;Reflux;
Example 16; Preparation of l-[(lalpha,5alpha,6alpha)-3-(2,4-difluorophenyl)-3-azabicyclo[3.1.0]hex-6-yl]-3-(3- isoxazol-3-yl)phenyl)urea:Step I:- 3-(dimethylamino)-l-(3-nitrophenyl)prop-2-en-l-one:To a solution of l-(3-nitrophenyl)ethanone (0.01212 mole) in toluene (50 mL), diisopropyl ethyl amine (0.02424 mole), or dimethylformamide dimethyl acetal (0.024 mole) are added and refluxed the reaction mixture for 4 hrs. The reaction mixture is then cooled to room temperature, quenched with water and extracted with ethyl acetate. The organic layer is then dried over Na2SO4 and concentrated. The crude material is then triturated with ethyl acetate and decanted the solvent to get pure product. 1H NMR (DMSO- d6): delta 2.97 (s, 3H); <n="40"/>3.19 (s, 3H); 5.90 (d, IH, J = 12 Hz); 7.71 (t, IH, J = 9 Hz); 7.81 (d, IH, J - 12 Hz); 8.32 (t, 2H, J = 6 Hz); 8.61 (s, IH).
11.34 g
In 5,5-dimethyl-1,3-cyclohexadiene; for 21.0h;Reflux;
10 g of 3-nitroacetophenone (60.6 mmol, 1 equiv.), 35.63 g of N, N-dimethylformamide dimethylacetal (181 mmol, 3 equiv.), and 50 ml of xylene were refluxed overnight (21 hours), a little raw material was not reacted and the reaction was stopped. The reaction solution was cooled and concentrated to remove xylene. 150 ml of petroleum ether was added to the residue, and a solid precipitated under stirring, followed by filtration to obtain 11.34 g of 3-dimethylamino-1-(3-nitrophenyl)-prop-2-en-1-one as a yellow solid.
With sodium hydroxide In methanol at 20℃; for 10h;
10 (E)-3-(3,4-dimethoxyphenyl)-1-(3-nitrophenyl)prop-2-en-1-one (3).
To the solution of 3,4-dimethoxybenzaldehyde 1 (60 g, 360 mmol) and 1-(3-nitrophenyl)ethan-1-one 2 (59.6 g, 360 mmol) in MeOH (1100 mL) was added NaOH (15 g) at 0° C. The resulting solution was stirred at rt for 10 h. The precipitate was collected to give compound 3 as a yellow solid (97 g, 86%). [M+Na]+=336.1
62%
With sodium hydroxide In ethanol; water at 20℃;
60%
With potassium hydroxide In ethanol at 20℃; for 16h;
56%
With potassium hydroxide In ethanol; water at 0 - 25℃; for 2h; Inert atmosphere;
With potassium formate;RuCl[(S,S)-(C2H5)2CHCH2SO2dpen](p-cymene); tetrabutylammomium bromide; In water; at 50℃; for 24h;Inert atmosphere;Product distribution / selectivity;
The reaction was carried out with the same conditions as in Comparative example I-1, except that 0.63 mg (1.0 mumol) of RuCl[(S,S)-(C2H5)2CHCH2SO2dpen](p-cymene) was used as the catalyst. GC analysis of the reaction product confirmed that 1-(3'-nitrophenyl)ethanol with 85.4% ee optical purity was produced at 65% yield. Comparison with Comparative examples I-1 and I-2 indicated the superiority of this complex.
With dimethylsulfide borane complex; In toluene; for 12h;Reflux;
General procedure: The chiral amine ligand 1 immobilized SBA-15 (4) (320 mg, 30 mol%) was dissolved in dry toluene. Borane dimethyl sulfide (BMS) (0.03, 0.3 mmol) was added dropwise and then the reaction mixture was refluxed for half an hour followed by the drop wise addition of acetophenone (0.025, 0.1 mmol). The reaction mixture was continuously refluxed for 12 hours, cooled to room temperature, and filtered. To the filtrate, 2 N HCl was added and extracted with dichloromethane. (R)-1-phenyl ethanol was separated by column chromatography with silica gel as an adsorbent and 98:2 hexane:ethyl acetate as an eluant.
With (2S)-1-[(2S)-2-[(diphenylphosphanyl)oxy]propyl][(1R)-1-phenylethyl]amino}propan-2-yl diphenylphosphinitobis[dichloro(eta6-p-cymene)ruthenium(II)]; isopropyl alcohol; potassium hydroxide; at 82℃; for 0.166667h;Schlenk technique; Inert atmosphere;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: a solution of the ruthenium complexes 5-8 (0.005mmol), KOH (0.025mmol) and the corresponding ketone (0.5mmol) in degassed isoPrOH (5mL) was refluxed until the reaction was completed. After this time, a sample of the reaction mixture was taken off, diluted with acetone and analyzed immediately by GC, conversions obtained are related to the residual unreacted ketone. Furthermore, 1H NMR spectral data for the resultant products were consistent with previously reported results
With (1R)-2-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-1-phenylethyldiphenyl phosphinito[dichloro(eta6-p-cymene)ruthenium(II)]; isopropyl alcohol; potassium hydroxide; at 82℃; for 0.75h;Schlenk technique; Inert atmosphere;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: asolution of the ruthenium complexes (5-8) (0.005 mmol), KOH(0.025 mmol) and the corresponding ketone (0.5 mmol) indegassed isoPrOH (5 mL)was refluxed until the reaction completed.A sample of the reaction mixture was taken off, diluted withacetone and analyzed immediately by GC, the conversions obtainedare related to the residual unreacted ketone. Furthermore, 1H NMRspectral data for the resultant products were consistent with previouslyreported results.
With 3-[(2S)-2-[(chloro(eta4-1,5-cyclooctadiene)rhodium)diphenyl phosphanyl]oxy}-3-phenoxypropyl]-1-methyl-1H-imidazol-3-ium chloride; isopropyl alcohol; potassium hydroxide; at 82℃; for 0.166667h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: asolution of the complexes 3-6 (0.00125 mmol), KOH (0.00625 mmol)and the corresponding ketone (0.25 mmol) in degassed isoPrOH (5 mL)was refluxed until the reaction completed. Then, a sample of the reactionmixture is taken off, diluted with acetone and analyzed immediatelyby GC, conversions obtained are related to the residual unreactedketone
With (S,E)-2-((4-boronobenzylidene)amino)-3-(4-hydroxyphenyl)propanoic acid; isopropyl alcohol; potassium hydroxide; at 82℃; for 14h;Schlenk technique;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction:1-4 (0.01 mmol), NaOH (0.05 mmol) and the corresponding ketone(1.00 mmol) in degassed iso-PrOH (10 mL) were refluxed until thereaction completed in a Schlenk tube. After the desired reactiontime, a sample of the reaction mixture is taken off, diluted withacetone and analyzed immediately by GC. Conversion to theproduct was calculated from integration of its GC peak relative tothat of residual unreacted ketone. Furthermore, 1H NMR spectraldata for the resultant products were consistent with previouslyreported results.
Stage #1: 4-iodo-N,N-dimethyl-1H-imidazole-1-sulfonamide With ethylmagnesium bromide In diethyl ether; dichloromethane for 0.5h;
Stage #2: 3-Nitroacetophenone In diethyl ether; dichloromethane at 20℃;
With (R)-2,2',6,6'-tetramethoxy-4,4'-bis(di-3,5-dimethylphenylphosphine)3,3'-bipyridine; phenylsilane; cobalt(II) diacetate tetrahydrate In toluene at 40℃; for 24h; Molecular sieve; Under air; optical yield given as %ee; enantioselective reaction;
99%
With D-glucose In aq. phosphate buffer at 25℃; for 24h; stereoselective reaction;
Preparative-Scale Synthesis of Enantiomeric β-Phenylalcohols (S)-2a-2i, (S)-2m and (S)-2n by Resting Cells
General procedure: For isolation and characterization of the bioreduction product, the reaction was performedon a preparative scale: 300 g resting cells of R. rubra AS 2.2241 were resuspended in 1000 mL of Na2HPO4-KH2PO4 buffer (100 mM, pH 7.0) with 50 g glucose and 10 mM of each substrate (1a-1i,1m and 1n). The reaction mixture was incubated at 25°C and shaken at 220 rpm for 24 h. The cellswere removed by centrifugation and the supernatant was saturated with NaCl. The supernatantwas extracted with EtOAc (1000 mL 3). The organic phases were washed with brine, dried overNa2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography onsilica gel (eluent: EtOAc/PE 1:20) to give the enantiomerically pure alcohols 2a-2i, 2m, 2n. The isolatedyield and ee of preparative-scale are comparable to those obtained from screening biotransformations.The spectroscopic data (1H and 13 C NMR, and HPLC retention times) of enantiomerically alcohols 2a-2i, 2m and 2n are in agreement with those obtained for racemic forms, as described in theSupplementary Materials.
95%
Stage #1: 3-Nitroacetophenone With copper acetylacetonate; (S)-Xyl-P-Phos In toluene at -20℃; for 12h;
Stage #2: With sodium hydroxide In water; toluene for 3h; optical yield given as %ee; stereoselective reaction;
95%
With formic acid; C20H23ClIrNO3; isopropylamine In dichloromethane at 20℃; enantioselective reaction;
93%
With sodium t-butanolate; <i>tert</i>-butyl alcohol; (S)-2,2',6,6'-tetramethoxy-4,4'-bis(di(3,5-xylyl)phosphino)-3,3'-bipyridine In toluene at 0℃; for 14h; enantioselective reaction;
91%
With whole cell of Weissella paramesenteroides N7 In water at 20℃; for 24h; Microbiological reaction; Green chemistry; enantioselective reaction;
89%
With Lactobacillus kefiri P2 at 25℃; for 64h; Green chemistry; Enzymatic reaction; enantioselective reaction;
General asymmetric bioreduction process
General procedure: Lactobacillus kefiri P2 was added from its glycerol stock by inoculation to 10mL MRS mixture (MgSO4.7H2O 11.5% (w/v), K2HPO4 2 g/L, pepton [Oxoid] 10 g/L, yeast extract 2% glucose, [Difco] 5 g/L, C2H3NaO2.3H2O 5 g/L, salt solution [MgSO4.7H2O 11.5% (w/v), triamonium citrate 2 g/L], Tween 80 1 mL/L) followed by 48 h growth at 37 °C. From this mixture, overnight grown bacterial cells were inoculated to 100m LMRS mixture at 10% concentration. Then, pH of medium was adjusted to 4.5 with 1M HCI. This mixture was shaken for 2 hours, and then 1 mmol of substrate (1-16) was directly added to this mixture and incubated on an orbital shaker at 150 rpm with an incubation temperature of 25 °C for 64 h incubation period. After the catalytic reaction was complete, the supernatant was separated. The aqueous phase was saturated with NaCI and extracted with dichloromethane. After the organic phases were combined, they were dried over anhydrous Na2SO4 and filtered to remove the salt. The liquid was removed in a vacuum to remove dichloromethane and the crude product was characterizedby NMR analysis. After the crude product was purified using column chromatography, ee was determined using chiral HPLC. The absolute configurations of the alcohols were determined by comparing the literature values of the specific rotation.
83%
With borane N,N-diethylaniline complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In toluene at 30℃; for 5.5h; Inert atmosphere;
A.1 Step 1: Synthesis of (S)-l-(3-nitrophenyl)ethanol.
To a solution of (/Z)-Mc-CBS (18.1 mL, 18.1 mmol) in anhydrous toluene (500 mL) was added bo ran c -A', L'-d i c th y 1 an i 1 i n c complex (32.6 g, 199 mmol) at 30 °C under nitrogen atmosphere and stirred 20 min. And then a solution of l-(3-nitrophenyl)ethanone (30.0 g, 182 mmol) in toluene (300 mL) was added dropwise over 5 h while maintaining the internal temperature at 30 °C. The mixture was stirred for another 30 min and monitored by TLC. The reaction was quenched by the addition of hydrochloric acid solution (4 N in methanol, 50 mL) and then diluted with water (200 mL). After General Work-up Procedure 1, the resulting residue was purified by trituration with 10% EtOAcEtOAc in petroleum ether to afford the title compound (25.0 g, 83%) as a light yellow solid. MS (ESI) calculated for (C8H9N03) [M+H]+, 168.1; found, 168.1.
80%
Stage #1: 3-Nitroacetophenone With (1R,2R)-N,N’-bis(3,5-di-tert-butylbenzyl)-1,2-diphenylethane-1,2-diamine; diethoxymethylane; zinc diacetate In tetrahydrofuran at 25℃; for 24h; Inert atmosphere;
Stage #2: With hydrogenchloride; water In tetrahydrofuran for 1h; enantioselective reaction;
78%
With glucose dehydrogenase; D-glucose; ketoreductase from Pichia glucozyma; nicotinamide adenine dinucleotide phosphate In aq. buffer at 30℃; Enzymatic reaction; enantioselective reaction;
76%
With Vigna radiata suspension cell culture In ethanol at 27℃; for 240h; Green chemistry; Enzymatic reaction; enantioselective reaction;
56%
With (-)-diisopinocamphenylborane chloride In tetrahydrofuran at -25℃;
With (-)-diisopinocamphenylborane chloride
With Lentinus strigellus In water at 28℃; for 72h; optical yield given as %ee; stereoselective reaction;
With copper (II)-fluoride; phenylsilane; (S)-2,2',6,6'-tetramethoxy-4,4'-bis(di(3,5-xylyl)phosphino)-3,3'-bipyridine In toluene at -20℃; for 24h; optical yield given as %ee; enantioselective reaction;
With Candida tropicalis CE017 at 28℃; for 216h; Microbiological reaction; Potato-dextrose medium; optical yield given as %ee; enantioselective reaction;
With phenylsilane; copper diacetate; (S)-2,2',6,6'-tetramethoxy-4,4'-bis(di(3,5-xylyl)phosphino)-3,3'-bipyridine In toluene at -20℃; for 12h; stereoselective reaction;
99 % ee
With C20H20Cl2N2ORuS2; isopropyl alcohol; potassium hydroxide at 82℃; for 14h; enantioselective reaction;
>99% ee
With glucose; glucose dehydrogenase from Bacillus subtilis CGMCC 1.1398; medium-chain dehydrogenase from Kuraishia capsulate CBS1993; NAD In aq. phosphate buffer for 16h; Enzymatic reaction; enantioselective reaction;
Substrate scope and enantioselectivity determination
General procedure: Substrate scope and enantioselectivity determination The relative activities of 26 substrates were measured using thepreviously described assay protocol with adjusted ratio of enzymeand substrate concentration. The a-chloroacetophenone activitywas assumed 100%.Enantioselectivity was determined by examining the reductionof aromatic ketones using an NADH-regeneration system consist-ing of the puried KcDH and glucose dehydrogenase (GDH) fromBacillus subtilis CGMCC 1.1398. The 1-mL reaction mixture con-tained 0.5 mM NAD+, 10 mM ketone, 1 U KcDH, 50 mg glucoseand 2 U GDH in 50 mM potassium phosphate buffer (pH 7.0). After16 h, the reaction sample was equally separated into two parts,with one terminated by adding an equal volume of methanol, fol-lowed by HPLC analysis to determine the conversion ratio, and theother extracted with ethyl acetate, followed by ee analysis. Meth-ods used for analysing chiral products using HPLC or GC aredescribed in Supplementary Table S1.
Multi-step reaction with 2 steps
1: (1R,2R)-N,N’-bis(3,5-di-tert-butylbenzyl)-1,2-diphenylethane-1,2-diamine; zinc diacetate / neat (no solvent) / 10 h / 25 °C / Inert atmosphere; Sealed tube
2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.08 h / 0 °C / Inert atmosphere
> 99 % ee
With halophilic alcohol dehydrogenase ADH2 from Haloferax volcanii; NADPH In ethanol; acetonitrile at 25℃; Enzymatic reaction; enantioselective reaction;
94 % ee
With hydrogen; C32H12BF24(1-)*C39H43IrN2P(1+) In isopropyl alcohol at 20℃; for 0.5h; enantioselective reaction;
Multi-step reaction with 2 steps
1: water; sodium formate / 37 °C
2: horseradish peroxidase; galactose oxidase M<SUB>3-5</SUB>; catalase / water / 37 °C / Resolution of racemate; Enzymatic reaction
With borane N,N-diethylaniline complex; (1S,2R)-1-amino-2-indanol; In tetrahydrofuran; at 0 - 20℃;
Example 1; To a solution of (IS, 2R)-(-)-cis-l-amino-2-indanol (1.49 g, 10 mmol) in tetrahydrofuran (100 mL), cooled to O0C, was added borane-N,N-diethylaniline complex (17.8 mL, 100 mmol) and the mixture was stirred at 00C for 1 hour. After this time a solution of 3'-nitroacetophenone (16.5 g, 100 mL) in tetrahydrofuran (300 mL) was added dropwise over 4 hours and the mixture was allowed to warm to room temperature over night with stirring. After this time the mixture was quenched by stirring with acetone (40 mL) for 1 hour after which it was concentrated under reduced pressure. The yellow residue was dissolved in toluene (250 mL) and washed sequentially with dilute aqueous sulfuric acid (IM, 4 x 100 mL), water (100 mL), saturated aqueous sodium hydrogen carbonate (100 mL), water (100 mL) and brine (100 mL). The organic solution was dried over MgStheta4 and concentrated under reduced pressure to give (lR)-l-(3-nitrophenyl)ethanol (14.3 g, 86%).
74%
With borane N,N-diethylaniline complex; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole; In toluene; at 30℃; for 5.5h;Inert atmosphere;
To a solution of S-Me-CBS (12.1 mL, 12.1 mmol) in anhydrous toluene (300 mL) was added borane-N,N-diethylaniline complex (21.7 g, 133 mmol) at 30 C under nitrogen atmosphere and stirred 20 min. And then a solution of l-(3-nitrophenyl)ethanone (20.0 g, 121 mmol) in toluene (200 mL) was added dropwise slowly over 5 h while maintaining the internal temperature at 30 C. The mixture was stirred for another 30 min and monitored by TLC. The reaction was quenched by the addition of a hydrochloric acid solution (4 N in methanol, 50 mL) and then diluted with water (150 mL). Following General Work-up Procedure 1, the resulting residue was triturated with 10% EtOAcEtOAc in petroleum ether to afford the title compound (15.0 g, 74%) as a light yellow solid. MS (ESI) calculated for (C8H9N03) [M+H]+, 168.1; found, 168.1.
With (2S)-1-[(2S)-2-[(diphenylphosphanyl)oxy]propyl][(1R)-1-phenylethyl]amino}pro-pan-2-yldiphenylphosphinitobis[dichloro(eta6-benzene)ruthenium(II)]; isopropyl alcohol; potassium hydroxide; at 82℃; for 0.0833333h;Schlenk technique; Inert atmosphere;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: a solution of the ruthenium complexes 5-8 (0.005mmol), KOH (0.025mmol) and the corresponding ketone (0.5mmol) in degassed isoPrOH (5mL) was refluxed until the reaction was completed. After this time, a sample of the reaction mixture was taken off, diluted with acetone and analyzed immediately by GC, conversions obtained are related to the residual unreacted ketone. Furthermore, 1H NMR spectral data for the resultant products were consistent with previously reported results
With (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yldiphenyl phosphinito[dichloro(eta6-benzene)ruthenium(II)]; isopropyl alcohol; potassium hydroxide; at 82℃; for 0.166667h;Schlenk technique; Inert atmosphere;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: asolution of the ruthenium complexes (5-8) (0.005 mmol), KOH(0.025 mmol) and the corresponding ketone (0.5 mmol) indegassed isoPrOH (5 mL)was refluxed until the reaction completed.A sample of the reaction mixture was taken off, diluted withacetone and analyzed immediately by GC, the conversions obtainedare related to the residual unreacted ketone. Furthermore, 1H NMRspectral data for the resultant products were consistent with previouslyreported results.
(3aS)-1-methyl-3, 3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole borane complex[ No CAS ]
[ 121-89-1 ]
[ 76116-24-0 ]
Yield
Reaction Conditions
Operation in experiment
In methanol; dichloromethane; ethyl acetate;
Step A: (R)-1-(3-nitrophenyl)ethanol To a solution of (S)-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c]- [1,3,2]-oxazaborole-borane (6.06 mmol) in CH2Cl2 (6 mL) at -20 C. was added a solution of 3-nitroacetophenone (6.06 mmol) in CH2Cl2 (6 mL) in a dropwise fashion over 30 min. The resulting mixture was stirred 45 min. longer then poured into cold methanol (-20 C.), and this mixture allowed to stir overnight while warming to room temperature. The mixture was then concentrated in vacuo then more methanol (100 mL) added and concentrated, and then added another 100 mL methanol and concentrated. The resulting crude was purified on silica gel in 60:40 hexanes:ethyl acetate to yield 0.98 g of the title compound. 1H NMR (500 MHz, CDCl3): delta 8.22 (m, 1H); 8.08 (m, 1H); 7.69 (d, J=7.8 Hz, 1H); 7.50 (t, J=7.8 Hz, 1H); 5.00 (m, 1H); 2.62 (s, 1H); 1.53 (d, J=7.1 Hz, 3H).
EXAMPLE 46 Preparation of N-(3-(1H-Pyrazol-3-yl)phenyl)acetamidine A solution of 5.0 g (30.3 mmol) of 3-nitroacetophenone in 16 ml of DMF was treated with 4.8 mL of (MeO)2 CHNMe2 and heated to 120 C. for 24 h. After cooling to 25 C., the reaction poured into 1N HCl and extracted with hexanes/EtOAc (1:1). The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated in vacuo to give 1.88 g (28%) of intermediate. A solution of 940 mg (4.27 mmol) of the above compound in 34 ml of MeOH and 8.5 ml of H2 O was treated with 0.855 ml (17.6 mmol) of H2 NNH2 oH2 O and heated at reflux for 2 h. After cooling to 25 C., the reaction was poured into 1N HCl and extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo to give 808 mg (100%) of 1-(1H-pyrazol-3-yl)-3-nitrobenzene.
With Nonafluorobutanesulfonyl fluoride; tert-butylimino-tri(pyrrolidino)phosphorane In tetrahydrofuran at -10 - 20℃;
36.4%
With pyridine
6 Synthesis of 3-nitrophenylacetylene
Example 6 Synthesis of 3-nitrophenylacetylene To a reaction vessel, 0.481 g (2.909 mmol) of 3-nitroacetophenone and 10 ml (10.826 mmol) of a DFI/acetonitrile solution 0.46 g (5.818 mmol) of pyridine were charged and reacted at 84° C. for 5 hours under nitrogen atmosphere. After finishing the reaction, formation of 3-nitrophenylacetylene (parent ion 147, base peak 101) was confirmed by GC-MS analysis of the reaction mixture. 3-Nitrophenylacetylene had the reaction yield of 36.4% and the reaction selectivity was 100%.
21%
5 Synthesis of 3-nitrophenylacetylene
Example 5 Synthesis of 3-nitrophenylacetylene To a reaction vessel, 1.32 g (8.0 mmol) of 3-nitroacetophenone and 5 ml of a DMFC/acetonitrile solution [1.22 g (8.0 mmol) as DMFC] were charged and reacted at 84° C. for 4 hours under nitrogen atmosphere. After finishing the reaction, formation of 3-nitrophenylacetylene (parent ion 147, base peak 101) was confirmed by GC-MS analysis of the reaction mixture. As a result of GC analysis, the reaction yield of was 21% and the reaction selectivity was 94%.
Multi-step reaction with 2 steps
1: pyridine; trichlorophosphate / toluene / 20 - 115 °C
2: sodium hydride / N,N-dimethyl-formamide; mineral oil / 5 h / 55 °C
Multi-step reaction with 2 steps
1: potassium iodide; dmap; tetra-(n-butyl)ammonium iodide / 120 - 150 °C / Green chemistry
2: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 60 °C / Green chemistry
With bromine; sodium sulfite; In 1,1,2-Trichloro-1,2,2-trifluoroethane;
EXAMPLE 15 A vigorously stirred mixture consisting of 2.5 ml (0.05 mole) of bromine trifluoride and 3.2 ml (0.056 mole) of bromine was added into an ice-water cooled three necked flask equipped with a magnetic stirrer and a condenser, containing a suspension of 36 gr (0.2 mole) 3-nitroacetophenone in 80 ml of freon 113. The addition was carried out dropwise with vigorous stirring while the temperature was kept under 20 C. After the addition was completed the crude reaction mixture was poured into a stirred icy 5% sodium sulfite solution. The organic layer was separated and the aqueous solution was extracted twice with 100 ml dichloromethane. The combined organic layer was washed with 5% sodium bicarbonate solution and successively with water. The organic phase was dried over anhydrous magnesium sulphate and the solvent evaporated. The residue was distilled under reduced pressure in order to get rid of unreacted substrate. The residue was recrystallized from toluene. 7.3 gr of 3-bromo-5-nitroacetophenone were obtained, 85% yield based on reacted substrate.
With Cu/Cr/Ni trimetallic oxide nanoparticles In neat (no solvent) at 100℃; for 2h;
2.5 General procedure for the synthesis of quinoline derivatives catalyzed by Cu/Cr/Ni trimetallic NPs
General procedure: A mixture of 2-aminoaryl ketone (1.0mmol), α-CH acid (1.0mmol) and Cu/Cr/Ni trimetallic (0.02g) was heated in a test tube under solvent-free conditions. The reaction progress was monitored by TLC. After completion of the reaction, 10mL of hot EtOH was added to the mixture, and the catalyst was recovered by centrifugation. The residue was concentrated under reduced pressure, and the resulting crude product was recrystallized from EtOH. All quinoline products are known and characterized by 1HNMR,13CNMR, and mp and their resulting data were compared with authentic ones reported in literature [12,
89%
With diphenyl hydrogen phosphate at 140℃; for 6h;
79%
With poly(ethylene glycol)-bound sulphonic acid In water at 60℃; for 0.833333h; Green chemistry;
With mercuric triflate In ethanol at 20℃; for 24h;
Representative experimental procedure: To a solution of phenylacetylene (225 mg, 2.2 mmol) in 3 mL ethanol, o-phenylenediamine (108 mg, 1.0 mmol) and Hg(OTf)2 (10 mg, 0.02 mmol) were added and stirred at room temperature for 6.5 h. Completion of the reaction was monitored by TLC. After completion of reaction, the reaction mixture was quenched with water, extracted with dichloromethane, dried over anhydrous sodium sulphate, and volatiles were removed. The crude residue was purified by short column chromatography over silica-gel (60-120 mesh) using 5% ethylacetate/petroleum ether mixture afforded 2-methyl-2,4-diphenyl-2,3-dihydro-1H-benzo[b][1,4]diazepine (3aa) (281 mg, 90%) as a yellow crystalline solid
Stage #1: 3-Nitroacetophenone With diethylamino-sulfur trifluoride In dichloromethane for 48h; Reflux;
Stage #2: With iron; ammonium chloride In ethanol; water at 20℃; for 18h;
Multi-step reaction with 2 steps
1: (bis-(2-methoxyethyl)amino)sulfur trufluoride / dichloromethane; methanol / 16 h / 60 °C / Sealed tube
2: hydrogenchloride; iron / water; ethanol / 2 h / 20 °C
Multi-step reaction with 2 steps
1: (bis-(2-methoxyethyl)amino)sulfur trufluoride / dichloromethane; methanol / 16 h / 60 °C / Sealed tube
2: hydrogen; iron / water; ethanol / 2 h / 25 °C
Multi-step reaction with 2 steps
1: (bis-(2-methoxyethyl)amino)sulfur trufluoride / 12 h / 80 °C
2: hydrogen / palladium 10% on activated carbon / methanol / 3 h
Multi-step reaction with 2 steps
1: (bis-(2-methoxyethyl)amino)sulfur trufluoride / toluene / 80 °C
2: tin(ll) chloride / ethanol / 1 h / Heating / reflux
Multi-step reaction with 2 steps
1: diethylamino-sulfur trifluoride / dichloromethane / 24 h / -78 - 26 °C
2: hydrogen / palladium on activated charcoal; ethylenediamine / methanol / 1551.49 Torr
Multi-step reaction with 2 steps
1: (bis-(2-methoxyethyl)amino)sulfur trufluoride; ethanol / dichloromethane; toluene / 48 h / 20 °C / Inert atmosphere
2: tin(II) chloride dihdyrate / ethanol / 1 h / Reflux
With hydrogen In isopropyl alcohol at 69.84℃; for 1h; Autoclave;
Experimental procedure
In a typical hydrogenation experiment, a known quantity of catalyst was charged with 300 ml of isopropyl alcohol (solvent) to the reactor and heated to the desired reduction temperature under slow stirring (300 rpm). An in situ reduction of the catalyst was performed by bubbling hydrogen gas at a flow rate of 280 cm3 min-1 through this mixture for 30 minutes while stirring at 800 rpm. A measured quantity of 3-nitroacetophenone (Aldrich, 99%) was added to 25 ml of isopropyl alcohol in a conical flask and heated until all the 3-NAP was dissolved. After the reduction process was completed, the stirrer was turned off and the reactor was purged with nitrogen twice and pressurised to 1 barg pressure. The contents were then heated to the desired reaction temperature under slow stirring. After reaching the desired temperature, the stirrer was turned off and the 3-NAP solution was added to the reactor vessel through the reactor inlet, which was then flushed with 25 ml of isopropyl alcohol to give a total reaction volume of 350 ml. The solution was stirred at 800 rpm for 5 s to allow mixing. The stirrer was then turned off and the reactor pressurised with N2 to 1 barg. A sample of 2.5 ml was withdrawn. The reactor was de-pressurised, before being purged twice with hydrogen then pressurised with hydrogen to the desired reaction pressure. Once the vessel was pressurised the reaction was started by switching the stirrer on at 1000 rpm: this was taken as the zero time of the reaction. The progress of the reaction was followed by withdrawing samples of 2.5 ml at different time intervals along the reaction period of 6 h. The moles of hydrogen consumed during the reaction were also monitored and recorded. The liquid samples were analysed using a Thermo Finnigan Focus GC equipped with an AS 3000 autosampler. The column was HP-1701, 30 m × 0.25 mm × 1 μm film thickness. FID temperature was 523 K, injector temperature was 503 K, and the column temperature was fixed at 433 K. The hydrogenation experiments were performed at 3-NAP initial concentrations of 0.0075, 0.015, and 0.0225 mol l-1, temperatures of 313, 323, 333, and 343 K, hydrogen pressures of 2, 3, 4, and 5 barg, and catalyst weights of 0.05 and 0.1 g. The conversion of 3-nitroacetophenone and the yields of 3-aminoacetophenone (3-AAP), 1-(3-aminophenyl) ethanol (3-APE), and 1-(3-aminocyclohexyl) ethanol (3-ACHE) were calculated using the following correlations:
With potassium hydroxide In methanol at 20℃; for 24h;
82%
With potassium hydroxide In ethanol; water at 20℃;
General procedure for synthesis of chalcones via Claisen-Schmidt condensation
General procedure: To a solution of 2,4,5-trimethoxy benzaldehyde (4mmol) and appropriate acetophenone (4mmol) in C2H5OH (25ml), 40% of aqueous KOH (2mmol) was added. The reaction mixture was stirred at r.t. till completion of reaction (monitored by TLC). Then the reaction mass was poured into ice water and neutralized with aqueous 10% HCl solution. The precipitate was filtered, washed with excess of water, dried and recrystallized from methanol to obtain pure chalcones.
Stage #1: isopropyl alcohol With [RuCl2(η6-p-cymene)(S)-N-((1-phenylethyl)carbamothioyl)furan-2-carboxamide]; potassium hydroxide at 20 - 82℃; for 0.166667h; Inert atmosphere;
Stage #2: 3-Nitroacetophenone at 85℃; for 24h; Inert atmosphere;
naphthalen-1-yl-acetic acid [1-(3-nitrophenyl)ethylidene]hydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79.9%
In ethanol;Reflux;
General procedure: solutionof acid hydrazide (0.01 mol) and appropriate benzaldehyde/acetophenone (0.01 mol) in ethanol was refluxed for 5-6 h. The precipitated title compounds were then filtered off, washed with water and recrystallized from ethanol.
(E)-1-(3-nitrophenyl)-3-(2,6-dimethoxyphenyl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
General procedure: A 50 mL flask was charged with substituted acetophenone (5 mmol) and a solution of sodium hydroxide (10 mmol) in a 4:1 (v/v) mixture of ethanol/H2O (25 mL), and the resulting mixture was stirred at room temperature for 5 min. A substituted benzaldehyde (5 mmol) was then added to the reaction, and the resulting mixture was stirred at room temperature. The reaction was then monitored byTLC using ethyl acetate/petroleum ether (1:4 or 1:2 v/v) as the solvent system. Upon completion of the reaction, the crude product was filtered off and recrystallized from a mixture of dichloromethane and ethanol or purified by column chromatography over silica gel eluting with a mixture of petroleum ether and ethyl acetate to give the pure product.
With C30H34ClN4Ru(1+)*F6P(1-); potassium hydroxide In toluene at 120℃; for 6h; Inert atmosphere; Sealed tube;
78%
With silver trifluoromethanesulfonate; lithium bromide In toluene at 70℃; for 8h; Green chemistry;
General AgOTf-Catalyzed reactionof 2-aminobenzyl alcohol 1 and ketone 2’ synthesis of substituted2-phenylquinolines procedure
General procedure: A test tube (25 mL) wascharged with 2-aminobenzyl alcohol 1 (0.5 mmol, 1 equiv), ketone 2’ (0.75 mmol,1.5 equiv), AgOTf (0.025 mmol, 5 mol %), LiBr (0.05 mmol, 10 mol%), and toluene (3 mL) were added. Themixture was stirred at 70 oC in air for 8 hours. The solvent wasremoved under reduced pressure, and the products were isolated by columnchromatography on silica gel (hexane/AcOEt = 30:1).
69%
With C18H11Cl3CuN4; sodium hydroxide In toluene at 85℃; for 18h;
52%
With C24H22N6Ni; potassium <i>tert</i>-butylate In toluene at 80℃; for 10h;
49%
With (6,8,15,17-tetramethyl-7H,16H-5,9,14,18-tetraaza-dibenzo[b,i]-cyclotetradecenato(2-)-k(4)-N,N',N'',N''')nickel(II); potassium <i>tert</i>-butylate In toluene at 90℃; Inert atmosphere; Schlenk technique; Sealed tube; Green chemistry;
26%
With dimethyl sulfoxide; potassium hydroxide at 120℃; for 12h;
With iodine; 4-aminobenzene sulfonic acid In dimethyl sulfoxide at 100℃; for 5h;
Typical Procedure for the Preparation of 2,5-Diphenyloxazole
General procedure: A test tube was charged with 1a (0.32 mmol), 2a (0.38 mmol), I2 (2.0 equiv.) and PABS (0.5equiv.). Then 2 mL DMSO was added to the reaction system. The reaction was stirred at 100 oCfor 5 h. After cooling to room temperature, the solvent diluted with 10 mL ethyl acetate andwashed with 5 mL brine and dried over anhydrous Na2SO4. After the solvent was evaporated invacuo, the residues were purified by column chromatography, eluting with petroleum ether/EtOAc to afford pure 3aa.
N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1-(1-(3-nitrophenyl)ethyl)piperidine-4-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
52%
To a solution of l-(3-nitrophenyl)ethan-l-one (150 mg, 0.91 mmol) and N-(5-(((5-(tert- butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)piperidine-4-carboxamide (345 mg, 0.91 mmol) in DCE (15 mL) was added titanium isopropoxide (294 mg, 1.03 mmol) and the reaction was refluxed for 3 h. The mixture was then allowed to cool to room temperature. To the resulting solution was added sodium cyanoborohydride (65 mg, 1.03 mmol) and the mixture was stirred at room temperature for 12 h. The reaction progress was monitored by TLC. The reaction mixture was quenched with saturated NH4C1 solution and extracted with ethyl acetate (2 x 20 mL). The combined organic solvents were dried over Na2S04 and concentrated under vacuum. The crude compound was purified by silica gel column chromatography eluting with 0-50 % ethyl acetate in n-hexane to afford the title compound (250 mg, yield 52%) as a brown sticky oil. LCMS: [M+H]+ = 530.10 ; Rt = 2.40 min
With oxygen; palladium diacetate; toluene-4-sulfonic acid; In tetrahydrofuran; for 8h;Reflux;
General procedure: A mixture of aryl ketones (1.0 mmol), 1,3-diaminopropane (1.3 mmol) and p-toluene sulphonic acid (1.0 mmol) was stirred under oxygen atmosphere in THF. In this Pd (OAc)2 (0.1 mmol) was added and reaction mixture was heated to reflux temperature for 8-12 h. After completion of the reaction (TLC), reaction mixture was cooled to room temperature and concentrated under reduce pressure. The resulting concentrated solution was further diluted with water and then extracted with ethyl acetate. The ethyl acetate layer was washed with Na2S2O3 solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure to get the crude product. The product was then purified by using silica gel column chromatography (Hexane-EtOAc).
1,1-difluoro-2-(3-nitrophenyl)propan-2-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With caesium carbonate; In dimethyl amine; at 20℃;Glovebox;
In the glove box,Cs2CO3 (0.6 mmol) and 3-nitroacetophenone (0.2 mmol) were weighed into a 25 mL reaction tube,Measure the amount of DMA (1 mL) into the reaction tube.A bromodifluoromethylphosphonium salt (0.6 mmol) was weighed,Treated with DMA (2 mL)Inhalation into the syringe.Stirred at room temperature,A DMA solution of bromodifluoromethylphosphonium salt was injected into the reaction tube at a rate of 0.5 mL / h with a syringe pump.After the injection, the reaction is over. The solution in the reaction tube was transferred to a separatory funnel, 15 mL of water was added, extracted three times with dichloromethane (10 mL x 3), and the organic phases were combined and washed three times with water (10 mL x 3). The final obtained organic phase was dried over anhydrous sodium sulfate, and the solid was filtered off, the solvent removed by rotary evaporation, on a silica gel column with n-pentane and ethyl acetate as eluent, to give the final isolated product difluoromethyl, yield 60% purity & gt; 99.9% (nuclear magnetic purity).
(2E)-1-(3-nitrophenyl)-3-(quinoxalin-2-yl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
This procedure is based on our previous report27 and vogels procedure36. To a conical flask containing NaOH solution (1.5eq, 10 mL H2O) was added substituted acetophenones (1mmole) in ethanol (10 mL), and the reaction mixture was stirred for 10 minutes to allow enolate formation, to this was added quinoxaline-2- carbaldehyde 1 (1mmole) and the reaction mixture was stirred till completion. After completion of the reaction, as monitored by TLC the reaction mixture was poured in an ice bath and was acidified using conc. HCl. The solid obtained was then filtered, dried and recrystallized using Ethanol. The quinoxalinyl chalcone 2a-n were then characterized using IR, NMR (1H, 13C) and HR-MS spectroscopy. The purity was checked by HPLC measurements using mobile phase consisting methanol and water in the ratio 90:10.
(E)-3,4-dimethyl-N’-(1-(3-nitrophenyl)ethylidene)-1H-pyrrole-2-carbohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
73%
In ethanol for 4h; Reflux;
3.3. General Procedure for the Synthesis of 3,4-Dimethyl-1H-pyrrole-2-carbohydrazides 5a-l
General procedure: To a solution of 3,4-dimethyl-1H-pyrrole-2-carbohydrazide (1 eq.) in a minimum volume ofethanol (~1.5 mL) was added a solution of a substituted acetophenone (4a-l, 1 eq.) in minimumethanol (~1.5 mL). The reaction mixture was refluxed for 4-5 h, then cooled to room temperature andpoured into ice cold water. The solid product suspended was collected by vacuum filtration and thendried at 70 C. The desired product was recrystallized from ethanol and dried.
1-(1-(3-nitrophenyl)ethylidene)-2-(perfluorophenyl)hydrazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With acetic acid In ethanol Reflux;
General procedure for the synthesis of compounds1-27
General procedure: (perfluorophenyl)hydrazone derivatives 1-27 were preparedby reacting perfluorophenylhydrazine (1 mmol) with different substituted aldehydes and acetophenones (1 mmol)in absolute ethanol (15 mL) with 2-3 drops of CH3COOH under reflex up to 25-45 min. Reaction completion wasmonitored through TLC analysis and the transparentcolored reaction mixture was kept at room temperature forcooling and dried up to afford crude products 1-27. Compoundswere crystallized in ethyl acetate. Reaction yield isin the range of 85-92%. For structure conformations, thesynthesized compounds were inspected using EI-MS and1HNMR analysis.
With potassium fluoride; Cu(2+)*2C12H8N2*2I(1-)*S8 In N,N-dimethyl-formamide at 100℃; for 18h;
General procedure for the esterification of ketones
General procedure: A mixture of ketone (0.5 mmol), tetraethyl orthosilicate (2 mmol, 0.41 g) and KF (2 mmol, 0.116 g) was mixed inthe presence of CuI (0.4 mmol, 0.019 g) and 1,10-phenanthroline(0.8 mmol, 0.036 g) in DMF (1.5 mL) under ambient atmosphere at 100 °C. The progress of the reaction was monitored by TLC. After completion of the reaction, the product was extracted with ethylacetate/water. The solvent was evaporated, and the product was purified by column chromatography over silica gel using n-hexane/ethylacetate(8:2) as the eluent. Ethyl 3-nitrobenzoate 1H NMR (500 MHz, CDCl3)δ;1.45 (t, J = 7.1 Hz, 3 H), 4.46 (q, J = 7.1 Hz, 2 H), 7.67 (t,J = 7.9 Hz, 1 H), 8.41 (m, 2 H), 8.88 (t, J = 1.9 Hz, 1H), 13CNMR (125 MHz, CDCl3)δ; 14.27, 61.95, 124.55, 127.30,129.58, 132.21, 135.28, 148.25, 164.47.
2-(3-nitrobenzoyl)-6-nitro-4(3H)-quinazolinone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
62%
With iodine; In dimethyl sulfoxide; at 20 - 110℃; for 2h;
0.9 g of 3-nitroacetophenone was dissolved in 10 mL of DMSO, and 0.8 g of iodine was slowly added.1.1g added dropwise at room temperature<strong>[16313-65-8]<strong>[16313-65-8]2-Amino-5-nitrobenzamid</strong>e</strong> dissolved in 10mLDMSO solution,The reaction was carried out at 110 C for 2 h.100 mL of water was added to the reaction system.Extracted with (3 × 40 mL) ethyl acetate.The iodine was removed by washing with (2 x 30 mL) saturated NaHSO3 solution.After washing with water, dry with anhydrous magnesium sulfate.Evaporate the solvent under reduced pressure.The residue was separated by chromatography (eluent: ethyl acetate: petroleum ether = 1:3).2-(3-nitrobenzoyl)-6-nitro-4(3H)-quinazolinone 1.3 g,Yield 62%,
N-(4-(3-nitrophenyl)-1,3-thiazol-2-yl)guanidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With Oxone; sodium bromide In methanol at 60℃; for 3h;
16 Example 16: Synthesis of N-(4-(3-nitrophenyl)-1,3-thiazol-2-yl)guanidine (Formula 23)
Combine 3-nitroacetophenone (0.66 g, 4.0 mmol)Dissolved in MeOH (40 mL),Add Oxone (2.70g, 4.4 mmol) sequentiallyAnd NaBr (0.45 g, 4.4 mmol),Add amidinothiourea (0.47 g, 4.0 mmol) toInto the mixture,Slowly increase to 60,The reaction is complete after refluxing for 3h,The reaction mixture is filtered,The filtrate was taken and concentrated in vacuo.Dissolve the crude product in water,Adjust the pH to 8-9 with ammonia water,There is solid precipitation,Suction filtration, take the filter cake, and dry. At last,The crude product obtained was recrystallized with MeOH,The product N-(4-(3-nitrophenyl)-1,3-thiazol-2-yl)guanidine (0.79g) was obtained with the following structure,The yield is 75%.
2-(9,10-dimethoxy-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-8-yl)-1-(3-nitrophenyl)ethan-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
Stage #1: berberine chloride With potassium hydroxide In water for 0.666667h;
Stage #2: 3-Nitroacetophenone In water for 0.333333h;
Synthesis of 8-substituted berberines 10-34 (General method).
General procedure: KOH (2 g) was added to a solution of berberinehydrochloride (1) (372 mg, 1.0 mmol) in EtOH or MeOH(25 ml) and H2O (15 ml), and the resulting mixture wasvigorously stirred for 40 min. Then, a solution of thecorresponding nucleophile (3 mmol) in EtOH or MeOH 10 ml) was added, and stirring was continued for another20 min. Next, the solution was poured into chilled H2O(250 ml). The formed precipitate was filtered off, washedon filter with warm H2O, and recrystallized from a H2O-MeOH, 1:1 mixture.
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