* 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 Organic Chemistry, 2009, vol. 74, # 8, p. 3229 - 3231
2
[ 63069-48-7 ]
[ 140-89-6 ]
[ 51618-29-2 ]
Yield
Reaction Conditions
Operation in experiment
92.3%
With copper(l) chloride In N,N-dimethyl-formamide at 110℃; for 6 h; Inert atmosphere; Sealed tube
General procedure: A 25 mL Wattecs reaction tube was charged with 2-haloaniline 1 (0.6 mmol), potassium O-ethyl dithiocarbonate 2 (1.8 mmol),CuCl (0.06 mmol), and DMF (2 mL). The reaction vessel was flushed with argon three times and sealed. Then the mixture was stirred electromagnetically in an oil bath at 110°C for 6 h.The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, and then HCl (3 mL, 3 mol/L) was added and stirred for another 30 min. The reaction mixture solution was extracted by ethyl acetate (3 × 20 mL). Subsequently, the combined organic solutions were dried by anhydrous sodium sulfate and the target product was purified by chromatography on a silica gel column (eluent: petroleum ether/ethyl acetate) togive the corresponding pure product 3. Complete characterization characterizationof the products (all known) is found in the Supplemental Materials (Figures S1–S13).
77%
With iron(III) trifluoride; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In N,N-dimethyl-formamide at 110℃; for 18 h; Inert atmosphere; Sealed tube
General procedure: A 25 mL reaction tube was charged with 2-haloaniline 1 (0.6 mmol), potassium o-ethyldithiocarbonate 2 (1.8 mmol), FeF3 (0.06 mmol), 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl (0.03 mmol) and DMF (4 mL). The reaction vessel was flushed with argon for three times and sealed. Then the mixture was stirred electromagnetically in an oil bath at 110 for 3 - 21 hours. The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, then 4 mL HCl (3mol/L) was added and stirred for 30 minutes. Then the reaction mixture solution was extracted by ethyl acetate (3*20 mL). Subsequently, the combined organic solution were dried by anhydrous sodium sulfate and the target product was purified by silica gel colum chromatography (eluent: petroleum ether / ethylacetate) to give the corresponding pure product 3.
Reference：
[1] Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 5, p. 699 - 701
[2] Synthetic Communications, 2015, vol. 45, # 20, p. 2378 - 2385
3
[ 75-15-0 ]
[ 873-38-1 ]
[ 51618-29-2 ]
Yield
Reaction Conditions
Operation in experiment
96%
With sodiumsulfide nonahydrate In N,N-dimethyl-formamide at 110℃; for 15 h; Sealed tube; Inert atmosphere
General procedure: A sealed tube (50 mL) was charged with 2-haloaniline 1a (2mmol), CS2 (10 mmol), Na2S (4mmol) and DMF (2 mL) at room temperature under an argon gas atmosphere and the tube was flushed with argon for three times and sealed. Then the mixture was stirred electromagnetically at 110 °C for 12 hours. The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, 2 mL HCl (3 mol/L) was added and stirred for 30 minutes. Then the reaction mixture solution was extracted by dichloromethane (3*20 mL). Subsequently, the combined organic solution were dried by anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel colum chromatography (eluent: petroleum ether / ethyl acetate) give the corresponding pure product 2a.
With sodiumsulfide nonahydrate In N,N-dimethyl-formamide at 110℃; for 12 h; Sealed tube; Inert atmosphere
General procedure: A sealed tube (50 mL) was charged with 2-haloaniline 1a (2mmol), CS2 (10 mmol), Na2S (4mmol) and DMF (2 mL) at room temperature under an argon gas atmosphere and the tube was flushed with argon for three times and sealed. Then the mixture was stirred electromagnetically at 110 °C for 12 hours. The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, 2 mL HCl (3 mol/L) was added and stirred for 30 minutes. Then the reaction mixture solution was extracted by dichloromethane (3*20 mL). Subsequently, the combined organic solution were dried by anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel colum chromatography (eluent: petroleum ether / ethyl acetate) give the corresponding pure product 2a.
With sodium hydrogen sulfide In water at 80℃; for 4 h; Green chemistry
127 mg (0.40 mmol) of 4,4'-dichloro-2,2'-dithiodiphenylamine and 11.2 mg (0.2 mmol) of NaHS were added to the reaction flask followed by the addition of 2.5 mL of H20 as a reaction solvent, Then injected into 97yL (l · 6mmol) of carbon disulfide, the reaction was stirred at 80 ° C for 4 hours after plate chromatography test found disulfide raw material reaction was complete, cooled to room temperature, extracted with ethyl acetate, and then using rotary evaporation The solvent was removed under reduced pressure to give the crude product. The crude product was eluted with methylene chloride and eluted with a gradient. After column chromatography (200-300 mesh silica gel), 122 mg of 6-chloro-2-mercaptobenzothiazole was obtained as a white powder with a purity of more than 99percent Isolated yield 75.6percent, mp 239-241.
Reference：
[1] Patent: CN105949147, 2016, A, . Location in patent: Paragraph 0059; 0060
6
[ 554-00-7 ]
[ 51618-29-2 ]
Reference：
[1] Patent: US4431813, 1984, A,
[2] Patent: US4431813, 1984, A,
7
[ 140-89-6 ]
[ 554-00-7 ]
[ 51618-29-2 ]
Reference：
[1] Synthetic Communications, 2007, vol. 37, # 3, p. 369 - 376
[2] Journal of Photochemistry and Photobiology B: Biology, 2011, vol. 103, # 3, p. 215 - 221
[3] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 4, p. 1617 - 1625
8
[ 75-15-0 ]
[ 106-47-8 ]
[ 51618-29-2 ]
Reference：
[1] Patent: US5451594, 1995, A,
9
[ 75-15-0 ]
[ 31183-89-8 ]
[ 10544-50-0 ]
[ 51618-29-2 ]
Reference：
[1] Green Chemistry, 2017, vol. 19, # 4, p. 1102 - 1108
10
[ 873-38-1 ]
[ 140-89-6 ]
[ 51618-29-2 ]
Reference：
[1] Archiv der Pharmazie, 2009, vol. 342, # 10, p. 605 - 613
11
[ 23474-98-8 ]
[ 75-15-0 ]
[ 51618-29-2 ]
Reference：
[1] Journal of Medicinal Chemistry, 1984, vol. 27, # 6, p. 810 - 812
[Referential Example 145] 6-Chloro-2-mercaptobenzothiazole Under ice cooling, a solution of p-chloroaniline (5.70 g) in acetic acid (7 ml) was added dropwise to disulfur dichloride (25.0 ml) over 30 minutes, followed by stirring at room temperature for 3 hours and then at about 80C for 3 hours. Benzene (50 ml) was added to the reaction mixture. The green crystals were collected by filtration and washed with benzene. The resulting crystals were dissolved in ice water (500 ml) and the solution was stirred for 1 hour. To the reaction mixture, a 6N aqueous solution of sodium hydroxide was added to make the mixture alkaline. Sodium bicarbonate (6 g) was then added and the mixture was stirred at 100C for 1 hour. Activated carbon was added to the reaction mixture, followed by Celite filtration. To the filtrate, carbon disulfide (2.70 ml) was added, followed by heating to about 50C. Stirring was then conducted for 1.5 hours. After cooling to room temperature, the reaction mixture was made acidic with 1Nhydrochloric acid. Colorless powder thus precipitated was collected by filtration and dried, whereby the title compound (1.30 g, 14%) was obtained. 1H-NMR (DMSO-d6) delta: 7.28(1H,d,J=8.3Hz), 7.45(1H,dd,J=8.3,2.0Hz), 7.86(1H,d,J=2.0Hz). MS (FAB) m/z: 202 [(M+H)+, Cl35], 204 [(M+H)+, Cl37]. Elementary analysis for C7H4ClNS2 Calculated: C, 41.68; H, 2.00; Cl, 17.58; N, 6.94; S, 31.80. Found: C, 41.64; H, 2.13; Cl, 17.83; N, 6.94; S, 31.70.
EXAMPLE 1C A general procedure (the `Herz process`) for the preparation of 2-mercaptobenzthiazoles from the corresponding 2-mercaptoaniline (and a procedure for preparing the 2-mercaptoaniline from the corresponding aniline) is illustrated by the following preparation of 6-chloro-2-mercaptobenzthiazole.
To a stirred solution of 4-chloroaniline (2.55 g) in acetic acid (5 cm3) was added sulphur monochloride (10 cm3) causing formation of a thick red slurry. The reaction was heated at 60 C. for 4 hours giving a mixture of green solid and a green solution. The mixture was diluted with hexane and the green solid was filtered off. The solid was taken into water and 2M NaOH was added and the mixture heated for 4 hours at 100 C. and then filtered through celite to give a pale pink filtrate. Carbon disulphide (2 cm3) was added to the filtrate and the reaction was heated at reflux for 15 hours. The mixture was cooled and acidlied to pH 1 causing formation of a thick yellow precipitate. Filtration and recrystallisation from ethanol/acetone/water gave 6-chloro-2-mercaptobenzthiazole as a white solid. 1 H NMR (DMSO): d 7.97 (1H, d), 7.58 (1H, dd), 7.41 (1 H, d). Mp 251-253 C. (dec).
(d) 6-Chloro-2-mercaptobenzothiazole (melting point: 257-295) is obtained in 91% yield in an analogous manner after a reaction lasting 16 hours, using 2,4-dichloroaniline.
With carbon disulfide; potassium carbonate; In N-methyl-acetamide; water;
(a) 91 g of carbon disulfide are added dropwise to a stirred suspension of 162 g of 2,4-dichloroaniline and 414 g of potassium carbonate in 1,000 ml of dimethylformamide at about 25-30 C. in the course of 40 minutes, under a nitrogen atmosphere. The mixture is then warmed to an internal temperature of 150 C. in the course of 2 hours, and this temperature is maintained for 16 hours. The batch is cooled and filtered and the filtrate is largely freed from dimethylformamide. 600 ml of water are added to the residue which remains, the mixture is acidified and the product which precipitates is filtered off and dried. 187.6 g (93.2% of theory) of 6-chloro-2-mercaptobenzothiazole of melting point 258 C. are obtained.
With copper(l) iodide; tetrabutylammomium bromide; sodium carbonate; In water; at 100℃; for 24h;Sealed tube; Green chemistry;
General procedure: To a 10 mL sealed tube with a stir bar were added CuI (0.05 mmol), Aryl iodides (0.6 mmol), 2-mercaptobenzothiazoles (0.5 mmol), and Na2CO3 (1.0 mmol), H2O (2 mL) and the mixture was stirred for 24 h at 100 C. The mixture was then cooled to rt and extracted with EtOAc (3 10 mL). The organic layers were combined,washed with sat. brine (2 10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by columnchromatography.
With copper(l) chloride; In N,N-dimethyl-formamide; at 110℃; for 6h;Inert atmosphere; Sealed tube;
General procedure: A 25 mL Wattecs reaction tube was charged with 2-haloaniline 1 (0.6 mmol), potassium O-ethyl dithiocarbonate 2 (1.8 mmol),CuCl (0.06 mmol), and DMF (2 mL). The reaction vessel was flushed with argon three times and sealed. Then the mixture was stirred electromagnetically in an oil bath at 110C for 6 h.The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, and then HCl (3 mL, 3 mol/L) was added and stirred for another 30 min. The reaction mixture solution was extracted by ethyl acetate (3 × 20 mL). Subsequently, the combined organic solutions were dried by anhydrous sodium sulfate and the target product was purified by chromatography on a silica gel column (eluent: petroleum ether/ethyl acetate) togive the corresponding pure product 3. Complete characterization characterizationof the products (all known) is found in the Supplemental Materials (Figures S1-S13).
77%
With iron(III) trifluoride; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 110℃; for 18h;Inert atmosphere; Sealed tube;
General procedure: A 25 mL reaction tube was charged with 2-haloaniline 1 (0.6 mmol), potassium o-ethyldithiocarbonate 2 (1.8 mmol), FeF3 (0.06 mmol), 2,2?-bis(diphenylphosphino)-1,1?-binaphthyl (0.03 mmol) and DMF (4 mL). The reaction vessel was flushed with argon for three times and sealed. Then the mixture was stirred electromagnetically in an oil bath at 110 for 3 - 21 hours. The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, then 4 mL HCl (3mol/L) was added and stirred for 30 minutes. Then the reaction mixture solution was extracted by ethyl acetate (3*20 mL). Subsequently, the combined organic solution were dried by anhydrous sodium sulfate and the target product was purified by silica gel colum chromatography (eluent: petroleum ether / ethylacetate) to give the corresponding pure product 3.
General procedure: Intermediate 11a-e (50.0 mmol) was dissolved in dimethylsulfate or dimethyl sulfate (50.0 mL), the reaction mixture wasrefluxed for 2-4 h. After cooling the product precipitated assolid and was isolated by filtration. The solid was washed withdiethyl ether. Yields: 55-83%.
With sodiumsulfide nonahydrate; In N,N-dimethyl-formamide; at 110℃; for 12h;Sealed tube; Inert atmosphere;
General procedure: A sealed tube (50 mL) was charged with 2-haloaniline 1a (2mmol), CS2 (10 mmol), Na2S (4mmol) and DMF (2 mL) at room temperature under an argon gas atmosphere and the tube was flushed with argon for three times and sealed. Then the mixture was stirred electromagnetically at 110 C for 12 hours. The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, 2 mL HCl (3 mol/L) was added and stirred for 30 minutes. Then the reaction mixture solution was extracted by dichloromethane (3*20 mL). Subsequently, the combined organic solution were dried by anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel colum chromatography (eluent: petroleum ether / ethyl acetate) give the corresponding pure product 2a.
With sodiumsulfide nonahydrate; In N,N-dimethyl-formamide; at 110℃; for 15h;Sealed tube; Inert atmosphere;
General procedure: A sealed tube (50 mL) was charged with 2-haloaniline 1a (2mmol), CS2 (10 mmol), Na2S (4mmol) and DMF (2 mL) at room temperature under an argon gas atmosphere and the tube was flushed with argon for three times and sealed. Then the mixture was stirred electromagnetically at 110 C for 12 hours. The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, 2 mL HCl (3 mol/L) was added and stirred for 30 minutes. Then the reaction mixture solution was extracted by dichloromethane (3*20 mL). Subsequently, the combined organic solution were dried by anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel colum chromatography (eluent: petroleum ether / ethyl acetate) give the corresponding pure product 2a.
With sodium hydrogen sulfide; In water; at 80℃; for 4h;Green chemistry;
127 mg (0.40 mmol) of 4,4'-dichloro-2,2'-dithiodiphenylamine and 11.2 mg (0.2 mmol) of NaHS were added to the reaction flask followed by the addition of 2.5 mL of H20 as a reaction solvent, Then injected into 97yL (l · 6mmol) of carbon disulfide, the reaction was stirred at 80 C for 4 hours after plate chromatography test found disulfide raw material reaction was complete, cooled to room temperature, extracted with ethyl acetate, and then using rotary evaporation The solvent was removed under reduced pressure to give the crude product. The crude product was eluted with methylene chloride and eluted with a gradient. After column chromatography (200-300 mesh silica gel), 122 mg of 6-chloro-2-mercaptobenzothiazole was obtained as a white powder with a purity of more than 99% Isolated yield 75.6%, mp 239-241.
N-(1H-benzimidazol-2-yl)-2-((6-chlorobenzothiazol-2-yl)thio)acetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With potassium carbonate; In acetone; for 6h;
A mixture of N-(1H-benzimidazol-2-yl)-2-chloroacetamide(1) (2.39 mmol, 0.5 g), appropriate mercapto derivatives (3.20 mmol) and K2CO3 (2.39 mmol, 0.24 g) in acetone was stirred for 6 hours. At the end of the period, the solvent was vaporised and the residue was washed with water and filtered. After dryness, raw product was recrystallised from alcohol. Some chemical properties were given in Table 1.
With 1.3-propanedithiol; dimethyl sulfoxide; potassium hydroxide; at 130℃; for 12h;Inert atmosphere;
General procedure: To a solution of benzothiazoles or benzoxazoles (1, 1 mmol) in DMSO (3 mL), was added KOH (280 mg, 5 equiv) and 1,3-propanedithiol (207 muL, 2 mmol). The reaction mixture was heated under argon at 130 C for 12 h. After cooling to room temperature, water (10 mL) was added. The pH of the reaction mixture was adjusted to 3-4 using 5% HCl. The resulting mixture was extracted with ethyl acetate (15 mL ×2). The organic layer was washed with water and brine, dried over anhydrous MgSO4 and concentrated using rotary evaporator. The crude product was purified by silica gel column chromatography using ethyl acetate/n-hexane as eluent to afford the corresponding heteroaryl thiols 3.
ethyl 4-(2-((6-chlorobenzo[d]thiazol-2-yl)thio)acetamido)-2-hydroxybenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
With potassium carbonate In tetrahydrofuran at 23℃; for 4.5h;
Synthesis of p-aminosalicylic acid azole derivatives TM4
General procedure: Add azole (RH), DMF and K2CO3 to the reaction flask and stir at room temperature.Intermediate IM2-2 was added, and transferred to a 45°C water bath for stirring, followed by TLC monitoring until the reaction ended. Stop stirring, add ice-cold saturated NaCl solution, 2N HCl solution to adjust pH 6-7, refrigerate. Suction filtration, the filter cake is washed with saturated brine (10mL×1), ice water (5mL×1),The crude product was obtained after vacuum drying, and column chromatography (PE/EA=10:1-1:3, v/v). When the azole is mercaptoazole, DMF is changed to tetrahydrofuran (THF), and it is dispersed with petroleum ether several times before column chromatography.The rest of the conditions or operations are the same as the above non-mercaptoazole. After drying, the target compound TM4 is obtained.The experimental conditions and results are shown in Table 2.
With water; sodium hydroxide In acetonitrile at 20℃; for 0.166667h;
4.4. General synthetic method of S- and O-CF2H derivatives
General procedure: A mixture of 8 or 10 (1 mmol), NaOH (11 mmol, 0.44 g) was dissolved in CH3CN (CH3CN/H2O 10/1, V/V, 11 mL) in an oven dried 50 mL round bottom flask containing a stir bar. Iododifluoroacetophenone (2) (2 mmol, 0.56 g), was added to the reaction mixture and stirred at room temperature for about 10 min. After the reaction was completed as indicated by TLC the reaction mixture was removed under reduced pressure. And then, the reaction mixture was diluted with water (50 mL) and extracted with EtOAc (25 mL x 3), followed by brine (50 mL). The organic extract was dried over NaSO4, filtered and evaporated under reduced pressure. The crude product was further purified by silica gel column chromatography using (pet ether/EtOAc) to furnish the S- and O-CF2H derivatives 9a-9h and 11a-11h.
2-[(6-chlorobenzo[d]thiazol-2-yl)thio]-2-fluoro-1-phenylethan-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With potassium carbonate In tetrahydrofuran at 20℃;
α-Fluoro-β-ketosulfides 3a-u; General Procedure
General procedure: A reaction tube containing a magnetic stir bar was charged with α-bromo-α-fluoroketone 1 (0.2 mmol, 1.0 equiv), sulfhydryl compound 2 (0.22 mmol, 1.1 equiv) and K2CO3 (0.22 mmol, 1.1 equiv). After THF (2.0 mL) had been added, the reaction tube was capped with a rubber stopper and the contents were stirred for 1-2 h at room temperature. The reaction mixture was then quenched with saturated aqueous NH4Cl solution and extracted with ethyl acetate. The combined organic phases were dried over Na2SO4, filtered and concentrated under vacuum. The crude product was purified by flash column chromatography on silica gel (PE/EtOAc = 20:1 to 100:1) to give the α-fluoro-β-ketosulfide 3a-u.
6-chloro-2-(3-methoxyphenylthio)benzo[d]thiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
53%
Stage #1: 6-chloro-2-mercaptobenzothiazole With dmap; N-chloro-succinimide; nickel dichloride In toluene at 40℃; for 0.333333h; Inert atmosphere;
Stage #2: diethyl(3-methoxyphenyl) aluminum In toluene at 40℃; for 0.166667h; Inert atmosphere;
4.4. General procedures for the coupling reaction of 2- Mercaptobenzo[d]thiazole/oxazoles with (hetero)Aryl aluminum
General procedure: Under a dry nitrogen atmosphere, NiCl2 (6.48 mg, 0.05 mmol), DMAP (12.2 mg, 0.1 mmol), 2-mercaptobenzo[d]thiazole/oxazoles (1.0 mmol) and NCS (1.1 mmol), 1.5 mL toluene were added in a reaction vessel, the resulted solution was stirred at 40 C for 20 min. Then, an (hetero)arylaluminum reagents (2.0 mmol) was added to the mixture solution and stirred for 10 min at 40 C. After completion the reaction, the mixture was diluted with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (3 15 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was subjected to flash column chromatography on silica gel (ethyl acetate and hexane 30:1 or 80:1) to afford the corresponding coupled products 3
Stage #1: 6-chloro-2-mercaptobenzothiazole With dmap; N-chloro-succinimide; nickel dichloride In toluene at 40℃; for 0.333333h; Inert atmosphere;
Stage #2: diethyl(p-methoxyphenyl)aluminum In toluene at 40℃; for 0.166667h; Inert atmosphere;
4.4. General procedures for the coupling reaction of 2- Mercaptobenzo[d]thiazole/oxazoles with (hetero)Aryl aluminum
General procedure: Under a dry nitrogen atmosphere, NiCl2 (6.48 mg, 0.05 mmol), DMAP (12.2 mg, 0.1 mmol), 2-mercaptobenzo[d]thiazole/oxazoles (1.0 mmol) and NCS (1.1 mmol), 1.5 mL toluene were added in a reaction vessel, the resulted solution was stirred at 40 C for 20 min. Then, an (hetero)arylaluminum reagents (2.0 mmol) was added to the mixture solution and stirred for 10 min at 40 C. After completion the reaction, the mixture was diluted with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (3 15 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was subjected to flash column chromatography on silica gel (ethyl acetate and hexane 30:1 or 80:1) to afford the corresponding coupled products 3
6-chloro-2-(2-methoxyphenylthio)benzo[d]thiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54%
Stage #1: 6-chloro-2-mercaptobenzothiazole With dmap; N-chloro-succinimide; nickel dichloride In toluene at 40℃; for 0.333333h; Inert atmosphere;
Stage #2: diethyl(2-methoxyphenyl)aluminium In toluene at 40℃; for 0.166667h; Inert atmosphere;
4.4. General procedures for the coupling reaction of 2- Mercaptobenzo[d]thiazole/oxazoles with (hetero)Aryl aluminum
General procedure: Under a dry nitrogen atmosphere, NiCl2 (6.48 mg, 0.05 mmol), DMAP (12.2 mg, 0.1 mmol), 2-mercaptobenzo[d]thiazole/oxazoles (1.0 mmol) and NCS (1.1 mmol), 1.5 mL toluene were added in a reaction vessel, the resulted solution was stirred at 40 C for 20 min. Then, an (hetero)arylaluminum reagents (2.0 mmol) was added to the mixture solution and stirred for 10 min at 40 C. After completion the reaction, the mixture was diluted with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (3 15 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was subjected to flash column chromatography on silica gel (ethyl acetate and hexane 30:1 or 80:1) to afford the corresponding coupled products 3
Stage #1: 6-chloro-2-mercaptobenzothiazole With dmap; N-chloro-succinimide; nickel dichloride In toluene at 40℃; for 0.333333h; Inert atmosphere;
Stage #2: diethyl(phenyl)aluminium In toluene at 40℃; for 0.166667h; Inert atmosphere;
4.4. General procedures for the coupling reaction of 2- Mercaptobenzo[d]thiazole/oxazoles with (hetero)Aryl aluminum
General procedure: Under a dry nitrogen atmosphere, NiCl2 (6.48 mg, 0.05 mmol), DMAP (12.2 mg, 0.1 mmol), 2-mercaptobenzo[d]thiazole/oxazoles (1.0 mmol) and NCS (1.1 mmol), 1.5 mL toluene were added in a reaction vessel, the resulted solution was stirred at 40 C for 20 min. Then, an (hetero)arylaluminum reagents (2.0 mmol) was added to the mixture solution and stirred for 10 min at 40 C. After completion the reaction, the mixture was diluted with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (3 15 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was subjected to flash column chromatography on silica gel (ethyl acetate and hexane 30:1 or 80:1) to afford the corresponding coupled products 3
6-chloro-2-(p-tolylthio)benzo[d]thiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
62%
Stage #1: 6-chloro-2-mercaptobenzothiazole With dmap; N-chloro-succinimide; nickel dichloride In toluene at 40℃; for 0.333333h; Inert atmosphere;
Stage #2: diethyl(4-methylphenyl)aluminum In toluene at 40℃; for 0.166667h; Inert atmosphere;
4.4. General procedures for the coupling reaction of 2- Mercaptobenzo[d]thiazole/oxazoles with (hetero)Aryl aluminum
General procedure: Under a dry nitrogen atmosphere, NiCl2 (6.48 mg, 0.05 mmol), DMAP (12.2 mg, 0.1 mmol), 2-mercaptobenzo[d]thiazole/oxazoles (1.0 mmol) and NCS (1.1 mmol), 1.5 mL toluene were added in a reaction vessel, the resulted solution was stirred at 40 C for 20 min. Then, an (hetero)arylaluminum reagents (2.0 mmol) was added to the mixture solution and stirred for 10 min at 40 C. After completion the reaction, the mixture was diluted with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (3 15 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was subjected to flash column chromatography on silica gel (ethyl acetate and hexane 30:1 or 80:1) to afford the corresponding coupled products 3
6-chloro-2-(4-chlorophenylthio)benzo[d]thiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
48%
Stage #1: 6-chloro-2-mercaptobenzothiazole With dmap; N-chloro-succinimide; nickel dichloride In toluene at 40℃; for 0.333333h; Inert atmosphere;
Stage #2: C10H14AlCl In toluene at 40℃; for 0.166667h; Inert atmosphere;
4.4. General procedures for the coupling reaction of 2- Mercaptobenzo[d]thiazole/oxazoles with (hetero)Aryl aluminum
General procedure: Under a dry nitrogen atmosphere, NiCl2 (6.48 mg, 0.05 mmol), DMAP (12.2 mg, 0.1 mmol), 2-mercaptobenzo[d]thiazole/oxazoles (1.0 mmol) and NCS (1.1 mmol), 1.5 mL toluene were added in a reaction vessel, the resulted solution was stirred at 40 C for 20 min. Then, an (hetero)arylaluminum reagents (2.0 mmol) was added to the mixture solution and stirred for 10 min at 40 C. After completion the reaction, the mixture was diluted with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (3 15 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was subjected to flash column chromatography on silica gel (ethyl acetate and hexane 30:1 or 80:1) to afford the corresponding coupled products 3
6-chloro-2-(4-fluorophenylthio)benzo[d]thiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
46%
Stage #1: 6-chloro-2-mercaptobenzothiazole With dmap; N-chloro-succinimide; nickel dichloride In toluene at 40℃; for 0.333333h; Inert atmosphere;
Stage #2: diethyl(4-fluorophenyl)aluminum In toluene at 40℃; for 0.166667h; Inert atmosphere;
4.4. General procedures for the coupling reaction of 2- Mercaptobenzo[d]thiazole/oxazoles with (hetero)Aryl aluminum
General procedure: Under a dry nitrogen atmosphere, NiCl2 (6.48 mg, 0.05 mmol), DMAP (12.2 mg, 0.1 mmol), 2-mercaptobenzo[d]thiazole/oxazoles (1.0 mmol) and NCS (1.1 mmol), 1.5 mL toluene were added in a reaction vessel, the resulted solution was stirred at 40 C for 20 min. Then, an (hetero)arylaluminum reagents (2.0 mmol) was added to the mixture solution and stirred for 10 min at 40 C. After completion the reaction, the mixture was diluted with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (3 15 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated in vacuum. The residue was subjected to flash column chromatography on silica gel (ethyl acetate and hexane 30:1 or 80:1) to afford the corresponding coupled products 3
With N-chloro-succinimide In acetonitrile at 20℃; for 0.5h;
7
Under an air atmosphere at room temperature, 0.5 mmol (101 mg) of p-6-chloro-2-mercaptobenzothiazole and 1.5 mmol (200 mg) of N-chlorosuccinimide were put into a round-bottomed flask, and about 2 mL of solvent acetonitrile was added. , stirred, and reacted at room temperature for half an hour. After the reaction was completed, the reaction solution was transferred to a 250 mL separatory funnel, extracted with ethyl acetate (30 mL × 3), and the upper organic phases were combined, dried, filtered, and distilled to obtain crude The product was finally separated by column chromatography to obtain the product, the ratio of passing through the column was PE:EA=90:1, and the product yield was 75% (81 mg). The product is a colorless oily liquid.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
