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Structure of 619-41-0 * Storage: {[proInfo.prStorage]}
* 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.
With dibromamine-T; sodium thiosulfate In water; acetone at 20℃; for 1.5 h;
General procedure: To a solution of olefin (1mmol) in acetone (3mL) and water (0.1mL), TsNBr2 (2.2mmol) was added at room temperature. After completion of reaction, sodium thiosulfate (200mg approx.) was added and the reaction mixture was stirred for another 10min. The reaction mixture was extracted with ethyl acetate, dried (Na2SO4) and concentrated. Purification of the crude product by flash chromatography on silica gel (230–400 mesh) with petroleum ether–EtOAc as eluent gave the pure product.
Reference：
[1] Tetrahedron Letters, 2015, vol. 56, # 2, p. 356 - 358
[2] Organic and Biomolecular Chemistry, 2016, vol. 14, # 48, p. 11389 - 11395
[3] Green Chemistry, 2013, vol. 15, # 8, p. 2175 - 2179
[4] Synlett, 2010, # 15, p. 2335 - 2339
[5] Organic Letters, 2015, vol. 17, # 11, p. 2704 - 2707
[6] Green Chemistry, 2016, vol. 18, # 6, p. 1455 - 1458
[7] Tetrahedron, 2017, vol. 73, # 40, p. 5827 - 5832
[8] Organic and Biomolecular Chemistry, 2017, vol. 15, # 46, p. 9889 - 9894
[9] Tetrahedron, 2018, vol. 74, # 27, p. 3602 - 3607
2
[ 33491-05-3 ]
[ 619-41-0 ]
Yield
Reaction Conditions
Operation in experiment
95%
at 40℃; for 6 h; Green chemistry
General procedure: A mixture of haloalkyne (0.5 mmol), AgF (5molpercent) and water (1 equiv.) in TFA (1 mL) was stirred at 40°C for 6h, after which TFA was distilled out for reuse. The residue was separated by column chromatography to give the pure sample.
90%
With indium(III) triflate; water In acetic acid at 100℃; Sealed tube
General procedure: The reaction mixture of In(OTf)3 (16.8mg, 0.03mmol), 1-haloalkynes (0.3mmol), H2O (0.9mmol), HOAc (0.6mL), in a 5mL sealed tube was stirred at 100°C and monitored periodically by TLC. Upon completion, HOAc was removed under reduced pressure using an aspirator, and then the residue was purified by flash chromatography (PE/EA) on silica gel to afford corresponding carbonyl compounds 2a–2ad.
Reference：
[1] Tetrahedron Letters, 2014, vol. 55, # 7, p. 1373 - 1375
[2] European Journal of Organic Chemistry, 2016, vol. 2016, # 1, p. 116 - 121
[3] Journal of Organic Chemistry, 2013, vol. 78, # 18, p. 9190 - 9195
[4] Tetrahedron, 2016, vol. 72, # 27-28, p. 3818 - 3822
[5] Chinese Journal of Chemistry, 2016, vol. 34, # 12, p. 1251 - 1254
3
[ 122-00-9 ]
[ 13664-98-7 ]
[ 619-41-0 ]
Yield
Reaction Conditions
Operation in experiment
90%
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.
35%
With trimethylsilyl bromide; potassium nitrate In dichloromethane at 20℃; for 16 h;
General procedure: In a Nalgene.(R). bottle, to acetophenone (2 mmol) in dichloromethane (10 mL), potassium nitrate (4 mmol) and chloro/bromotrimethylsilane (8 mmol) were added. The heterogeneous mixture was stirred vigorously at 60 °C (for chlorination) or room temperature (for bromination) until the reaction went to completion (monitored by 1H NMR spectroscopy). The reaction mixture was then filtered and solvent removed under reduced pressure. The chlorinated/brominated acetophenone derivatives were obtained upon purification by flash chromatography (silica gel) with hexane as eluent. The products were characterized by comparing their spectroscopic data with those of the authentic samples.
Reference：
[1] Chinese Chemical Letters, 2014, vol. 25, # 1, p. 179 - 182
[2] Synlett, 2005, # 17, p. 2664 - 2666
[3] European Journal of Organic Chemistry, 2006, # 2, p. 483 - 488
[4] European Journal of Organic Chemistry, 2006, # 2, p. 483 - 488
[5] Biochemistry, 2010, vol. 49, # 36, p. 7913 - 7919
[6] Tetrahedron Letters, 2011, vol. 52, # 11, p. 1217 - 1221
4
[ 122-00-9 ]
[ 619-41-0 ]
Yield
Reaction Conditions
Operation in experiment
94%
With Oxone; ammonium bromide In methanol for 2.5 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.
94%
With N-Bromosuccinimide; toluene-4-sulfonic acid In acetonitrile at 82℃;
General procedure: A solution of acetophenone 1a-e (10 mmol), N-bromosuccinimide (12 mmol) and p-toluenesulphonic acid (15 mmol) in acetonitrile (50 mL) was stirred for 4 h at reflux temperature. After completion, the reaction mass was allowed to reach ambient temperature and the solvent was evaporated. The residue was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous MgSO4 and the solvent was evaporated under reduced pressure. The product was purified by flash chromatography on silica gel, being eluted with a mixture of hexane/ethyl acetate (97:3).
94%
With N-Bromosuccinimide; toluene-4-sulfonic acid In acetonitrileReflux; Inert atmosphere; Schlenk technique
General procedure: N-bromosuccinimide (0.37 mmol) was added to the stirredsolution of acetophenone (2) (0.37 mol, 1 equiv) in acetonitrile(40 mL). The resulting reaction mixture was stirredfor 10–15 min. After that p-TsOH (0.74 mmol, 2 equiv) wasadded to the reaction mixture and refluxed for 4–5 h andmonitored by TLC. After completion of reaction, reactioncontent was brought to room temperature and washed withsaturated solution of sodium bicarbonate and extracted withethyl acetate (3 × 20 mL), organic layer was dried oversodium sulphate and concentrated under reduced pressure.The obtained residues were purified by column chromatographyusing silica 100–200 mesh size by ethyl acetate:hexane (4:96) mixture and pure compound was identified as2-bromo-1-phenyl-ethanone 3a–g.
93%
at 70℃; for 2 h; Green chemistry
The representative example of oxidative bromination is described as follows: A mixture of 1.2 g acetophenone 1a (10 mmol) and 0.121 g Cu(NO3)2•3H2O (0.5mmol) was stirred and an oxygen balloon (about 0.5–1 L) was attached to the reaction system. Then 8mol/L aqueous solution of hydrobromic acid (1.5mL, 12mmol) was added dropwise to the mixture. The reaction mixture was then stirred at 70°C and monitored by TLC or GC. After the completion of the reaction, the mixture was extracted with CH2Cl2. The organic extract was first washed with 5percent sodium sulfite, saturated sodium bicarbonate solution, and then water and finally dried over anhydrous magnesium sulfate. The solvent was removed under vacuum and the residue was purified by column chromatography (silica gel, petroleum ether/dichloromethane 3:1) to afford the product, α-bromoacetophenone (2a) in 1.81 g, yield: 91percent.
92%
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione In chloroform at 40 - 45℃; for 2.5 - 3 h;
4'-Methylacetophenone (402.6 g, 3 moles) and chloroform (1.6 L) was placed in a 3 L 3-necked flask fitted with a mechanical stirrer, a thermocouple connected to a heater controller, a condenser and a nitrogen sweep. The flask was initially placed in a water bath held at 40° C. Solid 1,3-N,N-dibromo-5,5-dimethylhydantoin (145.3 g, -0.5 mole) was added to the stirred solution followed by catalytic concentrated sulfuric acid (2.5 ml_). The temperature rose to 45° C. Once the temperature had decreased to ~40° C, the second portion of 1,3-N,N-dibromo-5,5-dimethylhydantoin (145.3 g, -0.5 mole) was added. Again, the temperature rose to 45° C and then slowly cooled back to -40° C whereupon the last portion of 1,3-N,N-dibromo-5,5-dimethylhydantoin (145.3 g, -0.5 mole) was added. A heating mantle was placed under the flask and the solution was held at 45° C with stirring until the orange color dissipated. The overall addition reaction time was 2.5-3 hours. The HPLC analysis of the crude bromoketone solution showed 5-6percent unreacted ketone, -2percent dibrominated product and -92percent α-bromo^'-methylacetophenone. The solid, 5,5-dimethyl-hydantoin, was removed by filtration and washed with chloroform (-200 mL). The chloroform filtrate containing the crude α- bromo-4'-methylacetophenone was placed in an addition funnel for transfer.
88%
With N-Bromosuccinimide; toluene-4-sulfonic acid In dichloromethaneIrradiation
General procedure: In a dry tube, substituted acetophenone (2 mmol), NBS (2 mmol) and PTSA (0.2 mmol, 10 molpercent) were added. 3-4 ml of anhydrous DCM was added and the tube was then irradiated in ultrasonic both till the completion of reaction (TLC). The reaction mixture was then cooled and extracted with 3 x 10 ml quantities of DCM. Organic layers were separated, dried over anhydrous MgSO4 and finally purified by silica gel chromatography [16].
84%
With tetra-n-butylammonium tribromide In methanol; dichloromethane at 20℃;
Example 2; 2-Bromo-1-p-tolyl-1-ethanone To a solution of 1-p-tolyl-ethanone (0.5 g, 4.16 mmol) in dichloromethane-methanol (50 ml-20 mL) was added tetrabutylammonium tribromide (2.2 g, 4.58 mmol) at room temperature. The mixture was stirred until the orange color faded. The solvent was then distilled under reduced pressure and the resulting precipitate was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and evaporated in vacuo to give a residue which was purified by flash column chromatography to yield the desired product 2-bromo-1-p-tolyl-1-ethanone (0.74 g, 84percent). 1H NMR (300 MHz, DMSO-d6) δ 2.39 (s, 3H), 4.89 (s, 2H), 7.37 (d, 2H), 7.89 (d, 2H); ESI-MS (MH+): 213 and 215.
84%
With hydrogen bromide; potassium iodide; sodium nitrite In water at 0 - 20℃; for 8 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).
80%
With N-Bromosuccinimide; toluene-4-sulfonic acid In acetonitrile at 85℃; for 4 h;
General procedure: A mixture of substituted arylethanones 14a-i (10 mmol), N-bromosuccinimide (1.4 g, 12 mmol) and p-toluenesulphonic acid (2.8 g, 15 mmol) in acetonitrile (50 mL) was stirred at 85 °C for 4 h. After completion of reaction (indicated by TLC), the reaction mass was allowed to reach ambient temperature and evaporated excess of acetonitrile under reduced pressure. The residue so obtained was mixed in water, extracted with ethyl acetate (2 × 50 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuuo. The crude product obtained was recrystallized from n-hexane to afford pure 1-aryl-2-bromoethanones 15a-i in 75-85percent yields.
73%
With N-Bromosuccinimide; toluene-4-sulfonic acid In acetonitrile at 80℃;
General procedure: A modified reaction route: NBS (1.2 equiv.) was added to a solution of appropriately substitutedacetophenones 9a–9l (1.0 equiv.) in CH3CN (15 mL) with p-TSA (0.2 equiv.). The solution washeated at 80 °C for 3-5 h until all the starting materials had been consumed (TLC monitored). Thereaction mass was poured in ice-cold water and extracted with DCM (3 × 20 mL). Anhydrous Na2SO4was added to the combined organic layer, filtered and the excess solvent was removed under reducedpressure. The resultant solid/ liquid obtained were washed with hexane to yield compounds 10a–10i.4,5
73%
With hydrogen bromide; bromine In methanol at 20℃; for 4 h;
5.36 g (0.04 mol) of p-methylacetophenone in a 100 ml round bottom flask,Add 40 ml of methanol to make the system uniform.Add a few drops of hydrobromic acid as a catalyst,Slowly add a solution of 2 ml (0.04 mol) of bromine in 20 ml of methanol under vigorous stirring at room temperature to control the drop rate.After the color of bromine disappears, add it again.After about 2 hours,Then continue the reaction at room temperature for 2 h,After the reaction is completed,Pour quickly into about 200 ml of ice water with stirring.A large amount of white flocculent or lumpy solid is produced, suction filtered, the filter cake is washed with water, and naturally dried overnight to obtain 7.8 g of a white solid.Melting point: 53 ° C,The yield was 73percent
65%
With bromine In acetic acid at 10 - 35℃; for 5 h;
Preparation 10: 2-Bromo-1- (4-methylphenyl)-1-ethanone To a stirring solution of 20 g (150 mmol) of 4-methylacetophenone in 100 mL of glacial acetic acid was added catalytic amount of HBr (0.5 mL) followed by 21.40g (134 mmol) of bromine dissolved in acetic acid (30 mL) dropwise at 10-15 °C. The reaction mixture was stirred at 25-35 °C for 5 hrs, then poured into water (100 mL). The solid that separated was filtered to give the required product (20 g, 65percent).
62%
With iodine pentoxide; potassium bromide In water at 20℃; for 23 h;
General procedure: A mixture of arene (0.5 mmol), I2O5 (334 mg, 1.0 mmol), and KBr (148 mg, 1.25 mmol) was dissolved in 2mL of H2O. The reaction was complete after stirring for the indicated time at room temperature. The mixture was extracted by ethyl acetate and concentrated under reduced pressure, and the mixture was purified by flash column chromatography (silica gel) to afford the desired product.
53%
With N-Bromosuccinimide In ethyl acetate at 40℃;
A 100 mL round bottom flask was charged with 10 mmol of 4-methylacetophenone and 11 mmol of N-bromosuccinimide (NBS).35mL of ethyl acetate dissolved,Then add 1g of Amberlyst 15 ion exchange resin as catalyst.The reaction was warmed to 40°C and reacted. After TLC tracks the reaction,The reaction solution was filtered to remove Amberlyst 15 ion exchange resin, and the filtrate was spin-dried.Column chromatography (eluent: petroleum ether/ethyl acetate) gave pale yellow crystals in 53percent yield.
53%
With N-Bromosuccinimide In ethyl acetate at 40℃;
In a 100 mL round-bottomed flask, 10 mmol of 4-methylacetophenone and 11 mmol of N-bromosuccinimide (NBS) were added.35mL of ethyl acetate dissolved,Then add 1g of Amberlyst 15 ion exchange resin as catalyst.The reaction was warmed to 40°C and reacted. After TLC tracks the reaction,The reaction solution was filtered to remove Amberlyst 15 ion exchange resin, and the filtrate was spin-dried.Column chromatography (eluent: petroleum ether/ethyl acetate) gave pale yellow crystals,Yield 53percent.
Reference：
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5
[ 17263-64-8 ]
[ 619-41-0 ]
Yield
Reaction Conditions
Operation in experiment
86%
With ferric(III) bromide; silica gel In dichloromethane at 20℃; for 0.166667 h;
General procedure: A 5mL round-bottom flask was charged with FeCl3 (0.25 mmol), silica gel (100mg) and DCM (2mL). Then a 1 mL dichloromethane solution with α-diazo-ketone (0.50 mmol) was slowly injected. After stirring for 10 mins under room temperature, the reaction mixture was concentrated in vaccuo and purified via column chromatography with 10:1 PE/EA to get the desired α-haloketone.
With oxone; 2-iodo-3,4,5,6-tetramethylbenzoic acid In water; acetonitrile at 25 - 30℃; for 10 h;
General procedure: To a solution of the olefin (0.5–1.2mmol) in 10–16mL of acetonitrile-water (1:1) mixture was added NBS (1.05equiv) at rt. The reaction mixture was stirred until all the olefin was consumed, as monitored by TLC analysis. Subsequently, TetMe-IA (10molpercent) and Oxone (1.0equiv) were introduced into the reaction mixture, and the stirring was continued. After completion of the oxidation as judged by TLC analysis, the reaction mixture was washed with saturated NaHCO3 solution. The organic matter was extracted 2–3 times with ethyl acetate or dichloromethane, and the combined organic extract was dried over anhyd Na2SO4. The solvent was removed in vacuo and the resultant residue was subjected to a short-pad silica gel column chromatography to isolate pure α-bromoketone.
Reference：
[1] Green Chemistry, 2017, vol. 19, # 8, p. 1983 - 1989
[2] Journal of Organic Chemistry, 2013, vol. 78, # 18, p. 9190 - 9195
[3] European Journal of Organic Chemistry, 2016, vol. 2016, # 1, p. 116 - 121
[4] Tetrahedron, 2016, vol. 72, # 29, p. 4151 - 4158
8
[ 51270-89-4 ]
[ 619-41-0 ]
Reference：
[1] Journal of the American Chemical Society, 2015, vol. 137, # 25, p. 8206 - 8218
9
[ 13664-98-7 ]
[ 619-41-0 ]
Yield
Reaction Conditions
Operation in experiment
170 mg
With water; sodium sulfite In ethyl acetate; acetone at 20℃;
General procedure: To a stirred solution of alkyne (1 mmol) in ethyl acetate(1 mL), 0.1 mL of acetone:water (1:1) and TsNBr2 (2 mmol) wasadded. After 10 min Na2SO3 (8 mmol) was added and the reaction was stirred at room temperature till completion asmonitored by TLC. The organic layer was extracted with ethylacetate, washed with water, dried with Na2SO4 and concentrated.The crude product was purified by flash chromatographyon silica gel (230-400 mesh) using petroleum ethereethyl acetateas eluent.
Reference：
[1] Journal of Organic Chemistry, 1987, vol. 52, # 14, p. 3143 - 3150
21
[ 67-66-3 ]
[ 7726-95-6 ]
[ 122-00-9 ]
[ 619-41-0 ]
Reference：
[1] Chemische Berichte, 1897, vol. 30, p. 576
[2] Bulletin de la Societe Chimique de France, 1897, vol. <3> 17, p. 909[3] Bulletin de la Societe Chimique de France, 1898, vol. <3> 19, p. 138
22
[ 7726-95-6 ]
[ 64-19-7 ]
[ 122-00-9 ]
[ 619-41-0 ]
Reference：
[1] Chemische Berichte, 1897, vol. 30, p. 576
[2] Bulletin de la Societe Chimique de France, 1897, vol. <3> 17, p. 909[3] Bulletin de la Societe Chimique de France, 1898, vol. <3> 19, p. 138
23
[ 7664-93-9 ]
[ 33491-05-3 ]
[ 64-19-7 ]
[ 619-41-0 ]
Reference：
[1] Annales de Chimie (Cachan, France), 1926, vol. <10> 5, p. 20
In ethanol; at 150℃; for 0.333333h;Microwave irradiation;
4,5,6,7-tetrahydrobenzo [d] thiazol-2-amine and 64 mg (0.3 mmol) of 2-bromo-4'-methylacetophenone were dissolved in 3 ml of ethanol and stirred in a microwave reactor at 150 C for 20 minutes. The residue was concentrated under reduced pressure and subjected to column chromatography (EtOAc: Hex = 1: 4) to obtain 2 g (22.3 mg, 28%) of the compound.
General procedure: To a solution of 2-bromo-4-hydroxyacetophenone 11 (20.0 mmol) in tetrahydrofuran (THF) (50 mL), hexamethylenetetramine(20.0 mmol) was added and stirred for 3 h at room temperature, and then the precipitated hexamethylenetetramine adduct 12 was filtered out. The adduct 12 was then heated with ethanol (80 mL) and concentrated HCl (8 mL) for 1 h at 45 C. After cooling, the inorganics were filtered out, the mixture was washed with ethanol (20 mL), and the solvent was distilled out completely under reduced pressure to obtain the desired compound 13. Then 14a-d (2.0 mmol), triethylamine (4.0 mmol), and EDCI·HCl (4.0 mmol), followed by HOBT (4.0 mmol), were added to a stirred solution of 13 (2.0 mmol) in CH2Cl2 (10 mL) and the mixture was stirred for 12 h at room temperature. Saturated Na2CO3 was added, the mixture was extracted with ethyl acetate, and the extracts were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by chromatography to give target compounds 15a-d.
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 4.16667h;
Step A: To a solution of <strong>[67344-77-8](3-bromo-benzyl)-methyl-amine</strong> (3.0 g, 15.0 mmol) in methylene chloride (60 mL) was added diisopropylethylamine (5.2 mL, 30.0 mmol). The reaction mixture was cooled to 00C and treated with 2-bromo-l-p-tolyl- ethanone (3.19 g, 15.0 mmol) portionwise over a period of 10 minutes. The reaction mixture was warmed to room temperature and stirred for 4 hours. The reaction mixture was washed with water (3x), dried over sodium sulfate, filtered, and the solvent was evaporated to afford 2-((3-bromobenzyl)(methyl)amino)-l-p-tolylethanone (4.89 g, 98percent) as a viscous, orange oil: 1H NMR (CDCl3, 500 MHz) delta 7.85 (d, J = 8.2 Hz, 2H), 7.51 (br s, IH), 7.38 (d, / = 7.9 Hz, IH), 7.287.23 (m, 3H), 7.17 (t, / = 7.8 Hz, IH), 3.78 (s, 2H), 3.63 (s, 2H), 2.41 (s, 3H), 2.35 (s, 3H).
With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;
Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.
4-(4-methylphenyl)-N-(4-methlphenyl)thiazol-2-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
In ethanol; at 70℃;
General procedure: The properly substituted bromoacetophenone 4, 6-15, 17-19 (1 equiv) and thioureas a-n (1 equiv) were solubilized in dry ethanol (5mLmmol-1 of bromoacetophenone) and reacted at 70C until consumption of the starting materials as indicated by TLC. After cooling, the solvent was evaporated and the residue obtained was washed with diethyl ether (3×10mL) to give the title compounds as a powder in good overall yields. In some cases, the crude material was purified by flash column chromatography. Yields, purification methods and purity are reported in details in the SI. Analytical data for compounds n, 6a, 8a, 15a, matched the data published previously [27,33,32,31].
With ethyloxirane; at 120℃; for 0.5h;Sealed tube; Microwave irradiation; Green chemistry;
General procedure: A stirred mixture of pyrimidine 1 (2.5 mmole), 2-bromoacetophenone 2 (2.5 mmole) and non-symmetrical electron deficient alkynes 3 (3.5 mmole) in 15 mL 1,2-epoxybutane was placed into an sealed microwave reactor at120 C for 30 min. The reaction mixture was cooled to room temperature, partly of the solvent was removed in vacuum, 5mL of MeOH was added under a gentle stirring and themixture was left overnight at 5-10 C . The solid formed was filtered-off, washed on the filter with a mixture of diethylether-MeOH 2:1 and crystallized from CHCl3/MeOH.
4,6-dimethyl-1-[2-(4-methylphenyl)-2-oxoethyl]-2-oxo-1,2-dihydropyridine-3-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
31%; 25%
4,6-Dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (20.0 g, 0.135 mol) was added to a solution of EtONa prepared from Na (3.1 g,0.135 mol) and EtOH (50 ml); the mixture was stirred for30 min, and the solvent evaporated to dryness. 4-Methylphenacyl bromide (28.8 g, 0.135 mol) and dry DMF (100 ml)was added to the resulting salt. The reaction mixture was heated on water bath at 80C for 2 h, cooled to room temperature, poured into ice water, and the formedprecipitate was filtered off. The mixture of N- and-alkylated isomers obtained in this way could be separated by two methods. Method I is based on differencein solubility of these substances (isomer 4b is less solublein CHCl3 and EtOAc than isomer 4). To separate theisomers, the obtained precipitate was placed on a Schott filter and washed with CHCl3-EtOAc, 1:1, several times.The substance remaining on the filter was recrystallized from EtOH. Method II involves the use of colum nchromatography (gradient eluting through SiO2, eluent CHCl3 followed by EtOAc).
With boron trifluoride diethyl etherate; In dichloromethane; at 130℃; for 0.25h;Microwave irradiation;
General procedure: A substituted amino unsaturated ketone (2, 1 mmol) and boron trifluorid ediethyletherate (10 mol%) in dichloromethane (5 ml) were added to a solution of substituted phenacyl bromide (1, 1 mmol) and the mixture was irradiated with microwaves for 10-16 min at 130C (250 W). After completion of the reaction, asindicated by TLC analysis, the reaction mixture was poured on to crushed ice, neutralized with sodium bicarbonate, extracted with ethyl acetate, and the extract was concentrated by rotary evaporation. The residue was purified by silica gel column chromatography with hexane-EtOAc (7:3) as eluent to afford the pyrrole derivatives 3.
7-(2-oxo-2-p-tolylethoxy)-4-(trifluoromethyl)-2H-chromen-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
With triethylamine; In tetrahydrofuran; at 20℃; for 24h;
General procedure: The appropriate bromoketone (6a-o) (1.7 mmol) and triethylamine (1.6 mmol) were added to as olution of either7-hydroxy-4-methyl-2H-chromen-2-one 4 (1.4 mmol)or <strong>[575-03-1]7-hydroxy-4-(trifluoromethyl)-2H-chromen-2-one</strong> 5 (1.4 mmol) in THF (20 mL). The mixture was stirred at room temperature for 24h, filtered and the solvent was evaporated under reduced pressure.The solid residue was purified by column chromatography eluting with DCM/MeOH 9:1 to afford (7a-n) and (8a-o).
4-(2-oxo-2-p-tolylethyl)-4,7-phenanthrolin-4-ium bromide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In acetonitrile; for 24h;Reflux;
General procedure: <strong>[230-07-9]4,7-Phenanthroline</strong> (28 mmol, 1 equiv.) was dissolved in 6 mL anhydrous acetonitrile.Then a reactive halide 30.8 mmol (1.1 equiv.) was added and the resulting mixture was stirredat reflux for 24 h. The formed precipitate was filtered and washed with acetonitrile and diethylether to give the desired product.
2-(4-fluorophenyl)-6-(4-methylphenyl)imidazo[2,1-b]-1,3,4-oxadiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
45.3%
In ethanol; for 0.00694444h;Microwave irradiation; Green chemistry;
1) added to the drying in the crucible 0.01mol a-bromo-p-methylacetophenone, 0.01mol 2-amino-5-(p-fluorophenyl)-1,3,4-oxadiazole is dissolved in anhydrous ethanol, get mixed solution A1, to a crucible of the reaction liquid is placed in the microwave oven, power modulation high fire files 700W, opening microwave oven radiation 25 seconds after the closing, of the crucible is taken out of the glass rod for stirring cooling, every 5 to detect reaction TLC (developing agent to volume ratio is: dichloromethane: methanol =10:1 mixture); 2) if the crucible is ethanol volatilizes in adding ethanol, to TLC detection reaction is complete, add water to the reaction solution of 15 ml, then the saturated NaOH solution for pH value adjusted to 7-8, to get mixed solution B1; 3) the mixture solution B1off the solvent in the, the cake is washed with water, drying to obtain the crude product, recrystallized to get DMF for 2-(4-fluorophenyl)-6-(4-methylphenyl)imidazo[2,1-b]-1,3,4-oxadiazole, yield 45.3%,
2,9,10-trimethoxy-3-p-methylphenylformylmethylenoxyprotoberberine chloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
38%
With potassium carbonate; In N,N-dimethyl-formamide;
General procedure: To a stirred solution of JTH (100 mg, 0.29 mmol) in anhydrous CH3CN or DMF, K2CO3 (122 mg,0.88 mmol) was added and heated to 70 °C. Then R1Br or benzyl chloroformate (2?4 eq) was added andstirred for 5?6 h. The mixture was cooled to precipitate completely, filtrated and washed by CH2Cl2 toafford compounds 5a?g.
8-bromo-6-chloro-2-(p-tolyl)imidazo[1,2-b]pyridazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76%
In isopropyl alcohol; at 90℃; for 16h;
N,N~ ~_J fixture of pyridazine 60a (800 mg, 3.9 mmol), 2-bromo-l-(£>- tolyl)ethan-l -one (850 mg, 4.29 mmol) was heated to 90 C in isopropanol (20 mL) for 16 h. Reaction mixture was cooled down and precipitated solid was filtered off, washed with isopropanol and diethyl ether. The obtained solid (950 mg, 76%) was immediately used without further purification. UPLC-MS: t = 5.19 (M+H, 322/324).
3-(4-hydroxy-3-(hydroxymethyl)butyl)-6-(p-tolyl)-3,5-dihydro-9H-imidazo[1,2-a]purin-9-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
General procedure: To a suspension of penciclovir (6) or hydroxybutylguanine (7)(0.2 g, 0.8 mmol or 0.9 mmol, respectively) in dry dimethylformamide(16 mL), sodium hydride (60% suspension in mineral oil, 1.2 eq.) wasadded and the reaction stirred at room temperature (21 C) for 1.5 h.Bromoketone (8) (1.3 eq.) was then added and the reaction stirred for6 h. Aqueous ammonia (25% solution 5 mL) was added to quench thereaction, which was concentrated under reduced pressure and the residualoil purified by flash column chromatography using gradientelution (CH2Cl2-MeOH). The obtained products were recrystallisedfrom a mixture of CH2Cl2 and MeOH.
1-(2-oxo-2-(p-tolyl)ethyl)-1H-pyrrole-2-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In acetonitrile; at 20℃; for 12h;
To a cold solution of hydroxylamine hydrochloride (0.38 g, 5.5 mmol, 1.1 equiv.) in anhydrous acetonitrile (50 mL), triethylamine (0.77 mL, 5.5 mmol, 1.1 equiv.) and 1H-pyrrole-2-carboxaldehyde (5.0 mmol, 1.0 equiv.) were added and stirred for around 30 mins. Then phthalic anhydride (0.75 g, 5.05 mmol, 1.01 equiv.) was slowly added under nitrogen protection. The resulting mixture was stirred at 80 C for about 8 h. After concentration, the resulting residue was added cold CH2Cl2 (30 ml × 3) and stirred. The combined filtrates were washed with 5% ammonia water to remove phthalic acid completely. The separated organic layer was dried over anhydrous Na2SO4, and then concentrated under reduced pressure. Finally the residue was purified by passing it through a short silica gel column using CHCl3 as eluent to give pure <strong>[4513-94-4]1H-<strong>[4513-94-4]pyrrole-2-carbonitrile</strong></strong> as yellow oil (80%).3 A mixture of <strong>[4513-94-4]1H-<strong>[4513-94-4]pyrrole-2-carbonitrile</strong></strong> (3.0 mmol, 1.0 equiv.), substituted methyl bromide (3.3 mmol, 1.1 equiv.) and K2CO3 (3.6 mmol, 1.2 equiv.) was stirred in CH3CN (20 mL) at room temperature. After being stirred for 12 h, the reaction mixture was concentrated under reduced pressure, diluted with EtOAc (30 mL), and washed with H2O (30 mL). The water layer was extracted with EtOAc (30 mL) one more time. The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane: EtOAc = 10:1) to afford 1b as white solid.
2-(4-fluorophenyl)-5-p-tolylimidazo[2,1-b][1,3,4]oxadiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
73.1%
In ethanol; for 0.35h;Microwave irradiation;
General procedure: The 2-Amino-5-aryl-1,3,4-oxadiazole (0.01 mol), α-bromoacetophenones derivatives (0.01 mol) and catalyst were treated by a microwave system for about the appropriate time. The microwave-accelerated reaction system was operated at 200 W. The progress of the reaction was monitored by TLC using dichloromethane/methanol (10:1) as eluent. After completion of the reaction, the solution pH was adjusted to 7-8. The crude product thus obtained was filtered, and recrystallized from N,N-Dimethylformamide to get the compounds (1a-1v).
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