* 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] Journal of Medicinal Chemistry, 1999, vol. 42, # 13, p. 2441 - 2446
[2] Justus Liebigs Annalen der Chemie, 1952, vol. 575, p. 162,167
[3] Journal of the Chemical Society, 1951, p. 485,489, 492
[4] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 8, p. 1800 - 1807
7
[ 110-91-8 ]
[ 555-16-8 ]
[ 6425-46-3 ]
Reference：
[1] Green Chemistry, 2013, vol. 15, # 5, p. 1159 - 1165
[2] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 15, p. 2239 - 2241
8
[ 555-16-8 ]
[ 16687-60-8 ]
Yield
Reaction Conditions
Operation in experiment
68%
With sodium azide; cerium(IV) tetraammonium sulfate dihydrate; hydroxylamine hydrochloride In N,N-dimethyl-formamide for 9 h; Reflux; Green chemistry
General procedure: Aldehyde (1 mmol), hydroxylamine hydrochloride (2 mmol) and sodium azide (2 mmol) were added successively to a solution of (NH4)4Ce(SO4)4·2H2O (20 molpercent) in 5 mL DMF. The mixture was reflux for appropriate time (Table 2). The progress of the reaction was monitored by TLC. After completion of the reaction, the solution was treated with HCl (4N, 10 mL) and then the solution was poured into 100 mL water and extract with ethyl acetate, washed several times with water. The combined organic mixture was dried over anhydrous Na2SO4, concentrated and the residue was purified by column chromatography on silica gel 60-120 mesh using petroleum ether/ethyl acetate (75:25) as eluent to afford the pure solid tetrazole. All the products were characterized by 1H NMR, 13C NMR and HRMS.
With Er(1,3,5-benzenetricarboxylate)(aqua)(N,N-dimethylformamide)1.1; ammonium acetate In ethanol at 70℃; for 4 h;
General procedure: Ammonium acetate (1 mmol), was added to the mixture of benzaldehyde (1 equiv), and ethyl acetoacetate (1.1 equiv) in Ethanol (1.5 mL) along with an appropriate amount of Er-MOF as catalyst (20 mg). The mixture was stirred at 70 °C for 4 h. After completion of the reaction, the catalyst was removed by centrifuge. Then brine (5 mL) and EtOAc (5 mL) was added. The mixture was extracted with EtOAc and the combined organic phase were washed with saturated aqueous solution of NaHCO3 (10 mL), and brine(10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. After removal of the solvent under vacuum, the crude product was purified by column chromatography to afford the desired product, Table 1. It is found that the Er-MOF catalyst can be recovered and reused five times without considerable loss of catalyticactivity.
95%
With C23H3BF16N2O; ammonium acetate In toluene at 100℃; for 10 h;
In the 100 ml flask is added in a single port 0.01 µM percent Lewis acid-base dual function catalyst I (wherein Rf=CF3; R1, R2, R3, R4, R5, R6=F), 0.1 µM to the nitrobenzene formaldehyde (R7=4 - NO2- Ph), 0.1 µM methyl acetoacetate (R8=Me; R9=Me), 0.1 µM ammonium acetate, 10 ml toluene, the reaction in the 100 °C stirring for 10 hours, TLC tracking reaction to the reaction is complete. The reaction result is: product II (R7=4 - NO2- Ph; R8=Me; R9=Me) of the yield is 94percent; catalyst system used repeatedly 10 times, its catalytic performance did not decline
95%
at 100℃; for 0.333333 h; Green chemistry
General procedure: To a glassy reactor equipped with a magnetic stir bar, amixture of aromatic aldehyde (1.0 mmol), β-keto ester(2 mmol), ammonium acetate (1.5 mmol) and n-Fe3O4(at)ZrO2/HPW (0.003 g, 15 mol percent) was added. The reactorwas put in an oil bath with the temperature of 100 °C andthe reaction was carried out under solvent-free condition.The progress of the reaction was monitored using TLCplates. When the reaction was completed, the mixture wasallowed to cool to room temperature. Afterwards, the mixturewas triturated with 5mL ethyl acetate and the catalystwas separated by the help of an external magnet. Then thesolvent was evaporated and the crude product was recrystallizedfrom EtOH/H2O to offer the pure product.
94%
for 2.25 h; Heating; Green chemistry
General procedure: A mixture of aldehyde 1 (1 mmol), 1,3-dicarbonyl compound 2 (2 mmol), and nitrogen source 3 (3 mmol) were mixed and heated in the presence of a low-melting sugar mixture.The progress of the reaction was monitored by thin-layer chromatography (TLC) using n-hexane–ethyl acetate (7:3) as the solvent system. The Rf values of the product spots ranged from 0.5 to 0.6. After completion of the reaction, water was added to the reaction mixture to obtain the solid product as a precipitate. In cases where the product was obtained as a melt, several washings with water followed by bicarbonate solution gave crystalline products. The solids were filtered and washed with cold water. In most of the cases, the product obtained was pure, and when impure, the product was recrystallized from hot ethanol. Further two products were obtained as oils (Table 5, entries 4w and 4x). These products were extracted with ethyl acetate and dried over anhydrous Na2SO4. Evaporation of the solvent gave the pure product as an oil.
92%
at 55℃; for 4 h; Green chemistry
General procedure: A mixture of aldehyde (1 mmol), β-dicarbonyl compound (1or 2 mmol), NH4OAc (2.5 mmol), dimedone (1 mmol, whenused), and SBA-15/NHSO3H (5 molpercent) was stirred at 55 °C.After complete disappearance of starting material asindicated by TLC, the resulting mixture was diluted with hotEtOAc (10 mL) and filtered. The catalyst was completelyrecovered from the residue.
82%
at 80℃; for 0.15 h;
General procedure: A mixture of the alkyl or aryl aldehyde (1 mmol), -dicarbonyl(2 mmol) and ammonium acetate (1.5 mmol) in the presence ofFe3O4NPs (0.024 g, equal to 10 molpercent) was heated at 80C, withstirring. The progress of the reaction was monitored by TLC (elu-ent: EtOAc:n-hexane). After completion of the reaction, the mixturewas cooled to room temperature and then ethanol was added tothe resulting mixture and separated Fe3O4NPs by a normal mag-net. After evaporation of solvent, the solid product was filtered andrecrystallized from ethanol to give the pure products in 72–95percentyields based on the starting aldehyde.
Reference：
[1] Chemical Communications, 2011, vol. 47, # 32, p. 9230 - 9232
[2] Tetrahedron Letters, 2010, vol. 51, # 8, p. 1187 - 1189
[3] Chemical Papers, 2011, vol. 65, # 6, p. 898 - 902
[4] Catalysis Letters, 2017, vol. 147, # 2, p. 453 - 462
[5] Patent: CN107141249, 2017, A, . Location in patent: Paragraph 0130; 0131
[6] Catalysis Letters, 2017, vol. 147, # 6, p. 1551 - 1566
[7] RSC Advances, 2014, vol. 4, # 21, p. 10514 - 10518
[8] Journal of the Chinese Chemical Society, 2016, vol. 63, # 4, p. 336 - 344
[9] Synthetic Communications, 2016, vol. 46, # 24, p. 1989 - 1998
[10] Journal of Heterocyclic Chemistry, 2005, vol. 42, # 5, p. 969 - 974
[11] Heteroatom Chemistry, 2006, vol. 17, # 4, p. 267 - 271
[12] Journal of Chemical Sciences, 2012, vol. 124, # 5, p. 1091 - 1096
[13] Research on Chemical Intermediates, 2014, vol. 40, # 1, p. 281 - 291
[14] RSC Advances, 2015, vol. 5, # 18, p. 13366 - 13373
[15] Monatshefte fur Chemie, 2006, vol. 137, # 1, p. 77 - 81
[16] Synlett, 2014, vol. 25, # 19, p. 2753 - 2756
[17] Advanced Synthesis and Catalysis, 2012, vol. 354, # 10, p. 2001 - 2008
[18] RSC Advances, 2014, vol. 4, # 100, p. 56658 - 56664
[19] Synthesis, 2007, # 18, p. 2835 - 2838
[20] Journal of Molecular Catalysis A: Chemical, 2014, vol. 382, p. 99 - 105
[21] Canadian Journal of Chemistry, 2017, vol. 95, # 5, p. 530 - 536
[22] Journal of Medicinal Chemistry, 1988, vol. 31, # 11, p. 2103 - 2107
[23] Organic Process Research and Development, 2001, vol. 5, # 4, p. 452 - 455
[24] Journal of Medicinal Chemistry, 1988, vol. 31, # 5, p. 936 - 944
[25] Synthesis, 2006, # 8, p. 1283 - 1288
[26] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1995, vol. 34, # 10, p. 920 - 922
[27] Synthetic Communications, 2010, vol. 40, # 16, p. 2457 - 2463
[28] Australian Journal of Chemistry, 2011, vol. 64, # 10, p. 1390 - 1396
10
[ 674-82-8 ]
[ 67-56-1 ]
[ 555-16-8 ]
[ 21829-09-4 ]
Yield
Reaction Conditions
Operation in experiment
80%
With ammonium acetate In neat (no solvent) at 60℃; Green chemistry
General procedure: In this work SBA-15 nanoreactor was synthesized by the procedure reported by Zhao et al. [6a] and then modified with mercaptopropyltrimethoxysilane (MPTMS) and oxidized to the sulfonic acid [6b] nanoparticle using hydrogen peroxide (Fig. 1). A mixture of diketene (3 mmol), aldehyde (1 mmol), enamine (1 mmol) and alcohol (4 mL) and SBA-15/SO3H (0.07 g, ~4 molpercent) was reacted under neat conditions for appropriate time (TLC). After that, 20 mL hot EtOH was added to the reaction vessel and, with simple centrifuging, the catalyst was removed as filtrate, washed and then the product recrystallized from hot ethanol. All of the products are synthesized by four-component method and were identified by their physical and spectral data (mp, IR, 1H NMR and 13C NMR).
Reference：
[1] Chinese Chemical Letters, 2012, vol. 23, # 8, p. 930 - 932
[2] Chinese Chemical Letters, 2013, vol. 24, # 5, p. 401 - 403
[3] Synthesis, 2010, # 23, p. 4057 - 4060
11
[ 60-35-5 ]
[ 555-16-8 ]
[ 105-45-3 ]
[ 21829-09-4 ]
Yield
Reaction Conditions
Operation in experiment
82%
With Candida antarctica lipase B immobilized on acrylic resin In tert-butyl methyl ether at 50℃; for 72 h;
Aldehyde (0.125 mmol), acetamide (0.5 mmol), and CAL-B (100 mg) in the mixed solvent (1 ml, 1,3-dicarbonyl compounds/methyl tert-butyl ether=4:6, by vol) at 50 °C for 72 h. The reaction was terminated by filtering off the enzyme. The crude residue was purified by silica gel column chromatography with an eluent consisting of petroleum ether/ethyl acetate (1/1 v/v). Product-contained fractions were combined, concentrated, and dried to give the product 1,4-dihydropyridine.
With ammonium acetate In neat (no solvent) at 55℃; for 4 h; Green chemistry
General procedure: Polyhydroquinolines and DihydropyridinesA mixture of aldehyde (1 mmol), β-dicarbonyl compound (1or 2 mmol), NH4OAc (2.5 mmol), dimedone (1 mmol, whenused), and SBA-15/NHSO3H (5 molpercent) was stirred at 55 °C.After complete disappearance of starting material asindicated by TLC, the resulting mixture was diluted with hotEtOAc (10 mL) and filtered. The catalyst was completelyrecovered from the residue
With C22H25F6N5S; ammonium acetate In dichloromethane at 20℃; for 1 h;
To a mixture of 0.014 g (0.1 mol) of dimedone, 0.01 mL (0.1 mol) of methyl acetoacetate, 0.015 g (0.1 mol) of p-nitrobenzaldehyde, and 0.096 g (0.125 mmol) of ammonium acetate at room temperature was added 1 mL of methylene chloride and 5 mmol of catalyst 5–9, the mixture was stirred for 1 h, then the solution was evaporated on a rotary evaporator. From the residue the reaction products were isolated by column chromatography, eluent ethyl acetate–hexane,1 : 8. Compounds were eluted in the following order: 4, 2, 3, and 1. Yield of compound 1 64–72percent.
Reference：
[1] Russian Journal of Organic Chemistry, 2016, vol. 52, # 5, p. 701 - 705[2] Zh. Org. Khim., 2016, vol. 52, # 5, p. 713 - 717,5
14
[ 105025-71-6 ]
[ 555-16-8 ]
[ 21829-09-4 ]
Reference：
[1] Journal of Materials Chemistry A, 2013, vol. 1, # 37, p. 11210 - 11220
15
[ 555-16-8 ]
[ 105-45-3 ]
[ 14205-39-1 ]
[ 21829-09-4 ]
Reference：
[1] Organic Process Research and Development, 2001, vol. 5, # 4, p. 452 - 455
[2] Synthetic Communications, 1995, vol. 25, # 6, p. 857 - 862
16
[ 555-16-8 ]
[ 105-45-3 ]
[ 21829-09-4 ]
Reference：
[1] Journal of Chemical Research, Miniprint, 1986, # 9, p. 2901 - 2915
Reference：
[1] Angewandte Chemie - International Edition, 2018, vol. 57, # 17, p. 4622 - 4626[2] Angew. Chem., 2018, vol. 130, # 17, p. 4712 - 4716,5
25
[ 555-16-8 ]
[ 100-27-6 ]
Reference：
[1] European Journal of Organic Chemistry, 2015, vol. 2015, # 32, p. 7009 - 7019
26
[ 555-16-8 ]
[ 528-75-6 ]
[ 610-30-0 ]
[ 62-23-7 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1992, # 2, p. 229 - 234
27
[ 555-16-8 ]
[ 124-40-3 ]
[ 15184-96-0 ]
Yield
Reaction Conditions
Operation in experiment
82%
Stage #1: at 20℃; for 0.166667 h; Stage #2: With sodium tris(acetoxy)borohydride; acetic acid In tetrahydrofuran; 1,2-dichloro-ethane at 20℃; for 1 h;
C-I) 4-Amino-dimethylbenzylamine7 g (46.3 mmol, 1 eq) 4-nitrobenzaldehyde are dissolved in 1 ,2-dichloroethane, then27.7 mL of dimethylamine (55.6 mmol, 1.2 eq, 2 molar solution in THF) are added and the solution is stirred for 10 min at RT. To this are then added, successively, 3.2 mL (55.6 mmol, 1.2 eq) acetic acid and 14.7 g (69.5 mmol, 1.5 eq) sodium trisacetoxyboro hydride and the reaction mixture is stirred for 1 h at RT. The reaction mixture is slowly poured into saturated, aqueous sodium hydrogen carbonate solution. The aqueous phase is washed twice with 100 mL of DCM and the combined organic phases are dried on magnesium sulphate. 6.9 g (38.1 mmol, 82percent) 4-nitro-dimethylbenzylamine are obtained, which is used in the following reduction without any further purification. MS-ESI+: 181 (M+H)+
With {(Pd{Fe(η5-C5H5)(η5-C5H3C(CH3)=NC6H4CH3-4)}(μ-Cl))2}; potassium carbonate In dimethyl sulfoxide at 110℃; for 12 h; Inert atmosphere
General procedure: Under N2 atmosphere, a reaction vessel was charged with a mixture of sodium sulfinates 1 (0.6 mmol), nitroarenes 2 (0.3 mmol), palladacycle I (0.75 molpercent) and K2CO3 (1.0 equiv) in DMSO (2 ml) at room temperature. After that, the mixture was heated to 110 °C and incubated in an oil bath for 12 h under N2 atmosphere. After the completion of the reaction, the reaction mixture was diluted with ethyl acetate and washed with brine three times. The combined organic solution was dried with Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by thin-layer chromatography on silica gel GF 254 (ethyl acetate/petroleum ether) to give the pure product.
Stage #1: at 0℃; for 0.25 h; Stage #2: With sodium tetrahydroborate In methanol; water at 20℃; for 2 h;
Preparation 33A; N-methyl(4-nitrophenv0methanamiπe; O2NNp-Nitrobenzaldehyde (15.0 g, 99.3 mmol) and 40percent aqueous methylamine (17 mL) were combined in MeOH (250 mL) for 15 min at 00C for 15 min and then treated with sodium borohydride (3.77 g, 99.3 mmol). The mixture was stirred at RT for 2 h and concentrated. Water (50 mL) was added to the residue which was then extracted with DCM (3 x 250 mL). The extracts were dried and concentrated giving the title substance. Yield 15. 4 g, 94percent. 1H NMR (CDCI3) δ 8.10 (m, 2H), 7.43 (m, 2H), 3.79 (s, 2H), 2.39 (s, 3H). MS (AP+) m/e 167 (MH+).
62%
Stage #1: at 80℃; for 24 h; Molecular sieve; Sealed tube Stage #2: With sodium tetrahydroborate In methanol at 0 - 20℃; for 24 h;
General procedure: The desired nitro-substituted benzaldehyde (1 eq, 13.2 mmol, 2.0 g), methylamine (40percent watersolution, 1.1 eq, 14.5 mmol, 0.95 mL) and molecular sieves (3A, 100 mg) were introduced in a screw cap vialand the mixture was heated at 80°C for 24h. After cooling to RT, the mixture was diluted with chloroform (3mL) and filtered. The solvent was removed by rotary evaporation and the crude obtained was redissolved inmethanol (30 mL) and cooled to 0 °C. NaBH4 (1.1 eq, 14.5 mmol, 550 mg) was added in three portions andthe resultant mixture allowed warming to RT and reacting for 24 h. The mixture was then quenched with aq.NH4OH 5percent (10 mL) and the solvent was concentrated by rotary evaporation. The obtained aqueous layer wasextracted with CH2Cl2 (3 x 10 mL). The combined organic extracts were dried over Na2SO4, filtered and thefiltrate was concentrated by rotary evaporation. The residue was purified by silica gel flash chromatographyor distillation under vacuum to give the title compound.
Reference：
[1] Tetrahedron, 2004, vol. 60, # 3, p. 569 - 575
[2] Chemistry - A European Journal, 2014, vol. 20, # 52, p. 17565 - 17571
[3] Journal of Medicinal Chemistry, 2016, vol. 59, # 6, p. 2747 - 2759
36
[ 593-51-1 ]
[ 555-16-8 ]
[ 19499-60-6 ]
Reference：
[1] Archiv der Pharmazie (Weinheim, Germany), 1987, vol. 320, # 7, p. 647 - 654
37
[ 555-16-8 ]
[ 5048-82-8 ]
Reference：
[1] Patent: WO2014/131855, 2014, A1,
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 19, p. 8967 - 9004
38
[ 555-16-8 ]
[ 27914-56-3 ]
Reference：
[1] Patent: JP5667058, 2015, B2,
39
[ 141-82-2 ]
[ 555-16-8 ]
[ 102308-62-3 ]
Yield
Reaction Conditions
Operation in experiment
69%
With ammonium acetate In butan-1-olReflux
General procedure: A mixture of appropriate aldehyde 2.40 g (1-15), 2.44 g ofmalonic acid and 3.54 g of ammonium acetate (1:1.1:2.3), in 200mLof the 1-butanol was refluxed for 1.5-2 h until the evolution of CO2ceased. The precipitate formed was filtered and washed withboiling 1-butanol (2 x 50 mL), boiling ethanol (2 x 50 mL) and100mL of water. Precipitates were dried at 80-100 °C for 8-10 h.Purity of product was checked by TLC, and yield obtained about65-80percent in each reaction.
Reference：
[1] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 252 - 268
40
[ 555-16-8 ]
[ 102308-62-3 ]
Yield
Reaction Conditions
Operation in experiment
14%
With ammonium acetate; malonic acid In ethanol; water
EXAMPLE 38 Preparation of N-(4-Cyanophenyl)-N--[3-(3-(4--nitrophenyl)propionic acid)]urea sodium salt A stirred suspension of ammonium acetate (30.8 g, 400 mmol) and 4-nitrobenzaldehyde (30.2 g, 200 mmol) in 50 mL of 95percent ethanol was heated to 45 °C. To the resulting thick slurry was added 75 mL of 95percent ethanol and malonic acid (20.8 g, 200 mmol). The reaction mixture was heated at reflux for 24 h. The cooled reaction mixture was filtered and the solid washed with copious amounts of ethanol. The solid was air-dried to afford 42.55 g of crude product as a pale orange powder. The crude product (35 g) was slurried in 300 mL of water, heated to 55°C, and the pH adjusted to 1 with concentrated HCl. After cooling to RT, the slurry was filtered and the solid washed with water. The filtrate was concentrated to approximately 250 mL and the pH adjusted to 7 with 1 N NaOH. The resulting suspension was stirred overnight and then filtered. The solid was dried in vacuo to afford 4.95 g (14percent) of 3-amino-3-(4--nitrophenyl)propionic acid as a white powder: 1H NMR (D2O/NaOD/TSP) δ 8.15 (d, J = 8.7 Hz, 2 H), 7.56 (d, J = 8.7 Hz, 2 H), 4.38 (t, J = 7.3 Hz, 1 H), 2.72-2.52 (m, 2 H); 13C NMR (D2O/NaOD/TSP) δ 182.2, 155.3, 149.3, 130.1, 126.6, 55.5, 49.5.
Reference：
[1] Russian Journal of Organic Chemistry, 2011, vol. 47, # 10, p. 1556 - 1563
[2] Journal of Medicinal Chemistry, 2017, vol. 60, # 21, p. 8801 - 8815
46
[ 109-01-3 ]
[ 555-16-8 ]
[ 70261-81-3 ]
Yield
Reaction Conditions
Operation in experiment
90%
With sodium tetrahydroborate; acetic acid In chloroform at 0 - 20℃; for 13 h;
General procedure: AcOH (100percent) (140 mL, 2.44 ml) was added over 1 h to a flask containing stirred NaBH4 (20.0 g, 0.53 ml) and CHCl3 (220 mL) at 0-5 °. The resulting mixture was stirred at 0-5 ° for 1.5 h and 1-methylpiperazine (1) (28.0 ml, 0.25 ml) and a solution of methyl 4-formylbenzoate (2a) (43.4 g, 0.26 ml) in CHCl3 (60 mL) were added. The resulting mixture was stirred at 0-5 ° for 1 h and then for 12 h at rt. the mixture was treated with H2O (150 mL) and Na2CO3 until pH 8.0-9.0. The aqueous phase was extracted with EtOAc (2 .x. 100 ml) then both organic layers were combined, washed with H2O (1 .x. 100 ml), and dried over anhydrous Na2SO4. Filtration and evaporation of the solvents gave methyl 4-[(4-methylpiperazin-1-yl)methyl]benzoate (4a): yellowish oil; yield: 61.6 g, 99percent.
Reference：
[1] Tetrahedron Letters, 2012, vol. 53, # 38, p. 5056 - 5058
[2] Russian Journal of Organic Chemistry, 2013, vol. 49, # 4, p. 563 - 567[3] Zh. Org. Khim., 2013, vol. 49, # 4, p. 580 - 584
[4] Journal of Medicinal Chemistry, 2017, vol. 60, # 21, p. 8801 - 8815
[5] Russian Journal of Organic Chemistry, 2011, vol. 47, # 10, p. 1556 - 1563
47
[ 109-01-3 ]
[ 555-16-8 ]
[ 7556-55-0 ]
[ 619-73-8 ]
[ 70261-81-3 ]
Reference：
[1] Chemistry of Heterocyclic Compounds, 2007, vol. 43, # 12, p. 1540 - 1543
48
[ 555-16-8 ]
[ 178265-65-1 ]
Reference：
[1] Journal of Physical Organic Chemistry, 2012, vol. 25, # 9, p. 754 - 759
[2] Organic and Biomolecular Chemistry, 2013, vol. 11, # 28, p. 4602 - 4612
[3] Journal of Catalysis, 2014, vol. 310, p. 37 - 44
[4] New Journal of Chemistry, 2016, vol. 40, # 7, p. 5775 - 5781
[5] Journal of Photochemistry and Photobiology A: Chemistry, 2018, vol. 351, p. 231 - 239
49
[ 555-16-8 ]
[ 118727-34-7 ]
Reference：
[1] Journal of the American Chemical Society, 2018, vol. 140, # 3, p. 984 - 992
50
[ 402-45-9 ]
[ 555-16-8 ]
[ 90035-20-4 ]
Yield
Reaction Conditions
Operation in experiment
69%
With caesium carbonate In N,N-dimethyl-formamide at 100℃; for 5 h; Inert atmosphere; Schlenk technique; Green chemistry
General procedure: Under an argon atmosphere, a Schlenk tube was charged with MCM-41-2N-Cu(OAc)2(46 mg, 0.025 mmol), nitroarene 1 (0.5 mmol), phenol 2 (1.0 mmol), Cs2CO3 (1.0 mmol) and DMF (3 mL). The reaction mixture was stirred at 100 °C for 5 h under Ar. After being cooled to room temperature, the mixture was diluted with ethyl acetate (20 mL) and filtered. The MCM-41-2N-Cu(OAc)2 catalyst was washed with distilled water (2 × 5 mL), DMF (2 × 5 mL) and EtOH (2 × 5 mL) and could be reused in the next run. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4. After removal of the solvent under reduced pressure, the residue was purified by column chromatography (EtOAc/hexane) on silica gel to afford the desired product 3.
62%
With copper(II) acetate monohydrate; caesium carbonate In N,N-dimethyl-formamide at 100℃; for 4 h; Inert atmosphere; Schlenk technique
General procedure: Under N2 atmosphere, a Schlenk tube was charged with nitroarenes 1 (0.5 mmol), phenols 2 (1.0 mmol), Cu(OAc)2·H2O (5 mol percent), and Cs2CO3 (1.0 mmol) in DMF (3 mL) at room temperature. After that, the mixture was stirred constantly at 100 °C (oil bath temperature) for 4 h. After the completion of the reaction, as monitored by TLC and GC–MS analysis, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtrated. The filtrate was concentrated under vacuum, and the resulting residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to afford the desired arylated product 3.
Reference：
[1] Journal of Chemical Research, 2017, vol. 41, # 12, p. 725 - 729
[2] Tetrahedron, 2012, vol. 68, # 43, p. 8905 - 8907
benzyl 6-(p-nitrobenzylideneamino)-penicillanate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
EXAMPLE 16 Benzyl-6-(p-Nitrobenzylideneamino)Penicillanate 6-Amino-penicillanic acid is converted to the benzyl ester thereof by reacting the parent compound with phenyldiazomethane following the general procedure of Example 1. The benzyl 6-amino-penicillanate is then reacted with p-nitrobenzaldehyde to form benzyl 6-(p-nitrobenzylideneamino)-penicillanate, using the general procedure of Example 2. The compound has a melting point of 90°-92° C. and nmr and ir analysis peaks are correct for the assigned structure.
(4-nitrophenyl)[2-(1-propyl)imidazolyl]methanol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
To a solution of <strong>[35203-44-2]<strong>[35203-44-2]1-propylimidazol</strong>e</strong> (8.0 g) in dry THF (100 ml), 1.6M n-butyllithium hexane solution (54.5 ml) was at 0°C under argon atmosphere. After the mixture was allowed to be at room temperature and was stirred for 2 hours, a solution of 4-nitrobenzaldehyde (9.97 g) in dry THF (100 ml) was added dropwise to the mixture at -78°C. The mixture was allowed to be at room temperature and was stirred overnight, and then, 1N hydrochloric acid was added to the mixture at 0°C. The mixture was neutralized with potassium carbonate, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the obtained residue was recrystallized from ethyl acetate-diisopropyl ether, to give (4-nitrophenyl)[2-(1-propyl)imidazolyl]methanol (5.26 g) as brown crystals. 1H-NMR (200 MHz, CDCl3) delta 0.77 (3H, t, J = 7.4 Hz), 1.42 to 1.72 (2H, m), 3.70 (2H, t, J = 7.4 Hz), 5.99 (1H, s), 6.86 (1H, s), 6.94 (1H, s), 7.54 (2H, d, J = 8.8 Hz), 8.20 (2H, d, J = 8.8 Hz). Elemental Analysis C13H15N3O3 Calcd. C, 59.76; H, 5.79; N, 16.08; Found. C, 59.85; H, 7.73; N, 16.04.
(3E,5E)-l-methyl-3,5-bis[(4-nitrophenyl)methylidene]azepan-4-one (compound No. 1563). N-methylazepan-4-one HCI (50 mg, 0.30 mmol) and 4-nitrobenzaldehyde were dissolved in acetic acid (5 mL) and stirred for 10 min, then cone. H2S04 (50 mu?) was added slowly and the mixture was stirred at rt overnight. More concentrated H2S04 (100 mu?) was added and stirring was continued at rt for 6 h. Additional 500 mu? of concentrated H2S04 was added and the reaction stirred overnight. A further 350 mu? of cone. H2S04 was added and stirring continued for additional 5 h, during which period further H2S04 was added in two portions (500 mu? and 250 mu?). Then water ( 3 x reaction volume) was added and the mixture was stirred until rt was reached. The reaction mixture was extracted with ethyl acetate (3 x reaction volume). The phases were separated and the organic phase concentrated to yield a dark yellow viscous oil. The crude product was purified by preparative HPLC, (XBridge column; eluents 50 mM ammonium carbonate buffer at pH 10 and methanol) giving the title product as a yellow solid (26.3 mg). LCMS System A: Rt 1.87 m/z [M+H]+ 394.1, System B: Rt 2.57.
General procedure: To a solution of the corresponding aromatic aldehyde (0.27 mmol) in EtOH (0.5 mL) was added urea (0.54 mmol) and CuSO4·5H2O (0.054 mmol). The mixture was stirred at 80 °C for 15 minutes before tetrahydrocurcumin or tetrahydrodemethoxycurcumin (0.27 mmol) was added. The reaction mixture was continued stirring for 24 hours and quenched with water (2 mL). The solution was washed with water (10 mL) and extracted with EtOAc (415 mL). The combined organic phases were washed with brine, dried over MgSO4 and concentrated under reduced pressure to afford crude product as a yellow brown oil. Purification was accomplished by column chromatography eluting with 60percent-75percent EtOAc/hexane to furnish compounds 8-17.
With triethylsilane; trifluoroacetic acid; In dichloromethane; for 1h;Cooling;
In an ice water bath, trifluoroacetic acid (4.4 g, 38.6 mmol), triethylsilane (9.02 g, 77.6 mmol), dichloromethane 15 mLwere added into a reaction vessel. After stirring for 5 min, a dichloromethane solution dissolving <strong>[3484-18-2]2-ethyl-1H-indole</strong> (3.74 g, 25.8 mmol) and p-nitro benzaldehyde (4.29 g, 28.4 mmol) was added dropwise slowly into the reaction vessel. After completion of dropwise addition it was reacted maintaining this temperature for 1 h, adjusted to pH=8-9 with 2 M solution of sodium hydroxide. An aqueous solution of sodium chloride was added, and extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate, concentrated to dryness to obtain a red brown solid, washed with a small amount of diethyl ether to obtain a yellow powdered solid 3 g, at a yield of 41.5 percent.
41.5%
With triethylsilane; trifluoroacetic acid; In dichloromethane; for 1h;Cooling with ice;
In an ice water bath, trifluoroacetic acid (4.4 g, 38.6 mmol), triethylsilane (9.02 g, 77.6 mmol), dichloromethane 15 mL were added into a reaction vessel. After stirring for 5 min, a dichloromethane solution dissolving <strong>[3484-18-2]2-ethyl-1H-indole</strong> (3.74 g, 25.8 mmol) and p-nitro benzaldehyde (4.29 g, 28.4 mmol) was added dropwise slowly into the reaction vessel. After completion of dropwise addition it was reacted maintaining this temperature for 1 h, adjusted to pH=8-9 with 2 M solution of sodium hydroxide. An aqueous solution of sodium chloride was added, and extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate, concentrated to dryness to obtain a red brown solid, washed with a small amount of diethyl ether to obtain a yellow powdered solid 3 g, at a yield of 41.5percent.
dimethyl (2E)-2-[hydroxy(4-nitrophenyl)methyl]-3-{(2-oxo-4-(trifluoromethyl)-2H-chromen-7-yl)oxy}but-2-enedioate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
50%
With triethylamine; In tetrahydrofuran; at 20℃;
General procedure: To a magnetically-stirred solution of 7-hydroxycoumarin derivatives (2 mmol), aromatic aldehydes (2 mmol) and NEt3 (2 mmol) in THF (8 mL) a mixture of dialkyl acetylenedicarboxylate (2 mmol) in THF (2 mL) was added in 15 min. The reaction mixture was then allowed to stand at room temperature for 0.5-10 h. After completion of the reaction as indicated by thin-layer chromatography (TLC) (n-hexane/EtOAc, 1:1), the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (Merck, 230-400 mesh) using a mixture of n-hexane/EtOAc (1:1) as eluent to afford the pure product as a light yellow powder.
di-tert-butyl (2E)-2-[hydroxy(4-nitrophenyl)methyl]-3-{(2-oxo-4-(trifluoromethyl)-2H-chromen-7-yl)oxy}but-2-enedioate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
30%
With triethylamine; In tetrahydrofuran; at 20℃;
General procedure: To a magnetically-stirred solution of 7-hydroxycoumarin derivatives (2 mmol), aromatic aldehydes (2 mmol) and NEt3 (2 mmol) in THF (8 mL) a mixture of dialkyl acetylenedicarboxylate (2 mmol) in THF (2 mL) was added in 15 min. The reaction mixture was then allowed to stand at room temperature for 0.5-10 h. After completion of the reaction as indicated by thin-layer chromatography (TLC) (n-hexane/EtOAc, 1:1), the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (Merck, 230-400 mesh) using a mixture of n-hexane/EtOAc (1:1) as eluent to afford the pure product as a light yellow powder.
(2R*,3R*)-methyl 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-hydroxy-3-(4-nitrophenyl)-2-phenylpropanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With indium(III) chloride; Rh2(OAc)4; In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; at 20℃; for 1h;Molecular sieve;
General procedure: To a stirred mixture of Rh2(OAc)4 (1 mol%), InCl3 (15 mol%), carbamate 1 (0.20mmol), aldehyde 2 (0.24mmol), and 4-MS (100mg) in DCM (1.5mL) was added diazo compound 3 (0.38mmol) in DCM (1mL) in portions at room temperature. After the addition of diazo compound was complete, the reaction mixture was stirred for 1h. Then, the reaction mixture was filtered and concentrated under reduced pressure. The crude product was subjected to 1H NMR analysis for the determination of diastereoselectivity. The crude product was purified by column chromatography on silica gel (eluent: EtOAc/light petroleum=1:20-1:10) to give the corresponding pure products 4.
6-fluoro-2-(2-(4-nitrobenzylidene)hydrazino)benzothiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation;
General procedure: A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized to give compounds 3-29.
In ethanol; at 70 - 80℃; for 3h;
General procedure: The mixture of <strong>[78364-55-3]6-fluoro-2-hydrazinylbenzo[d]thiazole</strong> (2) (0.01 mol) and benzalde-hyde/substituted benzaldehyde (0.01 mol) was reuxed in ethanol (15 ml) at 70?80 °C for 3 h. The separated product obtained was ltered off, washed withdistilled water and recrystallized from methanol to give the correspondinghydrazone. The product obtained was further dissolved in acetic acid (20 ml) atroom temperature followed by the addition of sodium acetate (0.5 g). Bromine(2 mmol) in acetic acid (10 ml) was added dropwise to the reuxing reactionmixture. After 1 h, the mixture was poured onto crushed ice (100 g). The precipitateobtained was ltered off and crystallized from ethanol-dimethylformamide (1:1) togive crystals of (3a?3t).
dimethyl (2-methyl-3-(trifluoromethyl)phenylamino)(4-nitrophenyl)methylphosphonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
With chitosan; In neat (no solvent); at 75℃; for 0.0333333h;Microwave irradiation; Green chemistry;Catalytic behavior;
General procedure: An equimolar mixture of <strong>[54396-44-0]2-methyl-3-(trifluoromethyl)aniline</strong> (0.351 g, 0.002 mol), corresponding aldehyde (0.002 mol), dimethyl phosphite (0.18 ml, 0.002 mol) and chitosan catalyst (10 molpercent) were taken in a reaction glass tube, degassed for 10 min and microwave irradiated at 180 W for 2 min at 60 °C. The progress of the reaction was monitored by TLC using petroleum ether and ethyl acetate (3:7) as solvent. After completion of the reaction, the mixture was diluted with ethyl acetate, washed with water (2 x 15 ml) followed by brine (1 x 10 ml), dried over Na2SO4 and evaporated to dryness. The crude mass was purified by column chromatography on silicagel (100-200 mesh) by using a 7:3 mixture of ethyl acetate in hexane to afford the pure alpha-aminophosphonates. Dimethyl (2-methyl-3-(trifluoromethyl) phenylamino)(4-nitrophenyl)methylphosphonate (4a) Yellow solid; Yield: 98percent. M.p.132?134 °C. IR (cm-1): m 3420 (NH), 2851 (C-H), 1000 (C-F), 1232 (P=O). 1H-NMR (DMSO-d6): d 8.23 (d, J = 8.8 Hz, 2H, Ar-H), 7.86-7.89 (m, 2H, Ar-H), 7.11 (t, J = 16.0 Hz, 1H, Ar?H), 7.00 (d, J = 8.0 Hz, 1H, Ar?H), 6.81 (d, J = 8.0 Hz, 1H, Ar?H); 5.92 (s, 1H, NH), 5.58 (d, J = 23.2 Hz, 1H, P-C-H), 3.76 (d, J = 10.8 Hz, 3H, P-OCH3), 3.57 (d, J = 10.4 Hz, 3H, P-OCH3), 2.35 (s, 3H, CH3). 13C-NMR (CDCl3): d 147.82(C6),143.90(C15), 143.06(C11), 128.47(C17 & C13), 126.50(C4), 123.61(C14 & C16),121.36(C18), 116.21(C1), 114.54(C5), 56.44(C9), 54.77(C23), 53.94(C25), 12.32(C7). 31P-NMR (CDCl3): d 25.24. 19F-NMR (CDCl3): d -59.86. MS (ESI): m/z419[M + H]+, 441[M + Na]+ Anal. Calcd. for C17H18F3N2O5P: C, 48.81; H, 4.34; N, 6.70. Found C, 48.03; H, 4.74; N, 6.48.
5,5-dimethyl-2-(2-(4-nitrophenyl)-1H-imidazol-5-yl)-2,5-dihydrothiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
37%
With silica-gel-supported sulfuric acid; ammonium acetate; In neat (no solvent); at 130℃; for 2h;
General procedure: To a mixture of aldehyde (1 mmol), <strong>[551-16-6]6-aminopenicillinic acid</strong> (1 mmol), and ammonium acetate (3 mmol), SiO2*H2SO4 (0.025 g) was added and heated in an oil bath up to 130 C in appropriate times. After the completion of the reaction (TLC monitoring, EtOAc: hexane 10/90 v/v), the mixture was diluted in hot ethanol, solid was filtered, and products were purified by recrystallization in watery ethanol.
3-(4-methoxy-benzo[d]thiazol-2-yl)-2-(4-nitrophenyl)thiazolidin-4-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
In ethanol; at 100℃; for 0.5h;Sealed tube; Microwave irradiation;
General procedure: All microwave irradiation experiments were carried out in CEM-Discover monomode microwavedevice, operating at a frequency of 2.45 GHz. Substituted aminobenzothiazole, equimolar amount ofsubstituted benzaldehyde (1.5 mmol) and mercaptoacetic acid in absolut ethanol (3 mL) were placed ina 10 mL reaction vial containing a stirring bar. The vial was sealed with a Teflon septum and placedinto the microwave cavity. It was irradiated at 100 C using 100 W as maximum power for 30 min.at the end of the reaction the mixture was rapidly cooled with gas jet cooling to room temperature.The clean product was obtained after filter under reduced pressure.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
100K+ Compounds
Competitive Price
1-2 Day Shipping
