There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
USD 200+
Structure of 95-16-9 * 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.
Reference：
[1] Phytochemistry, 2012, vol. 74, p. 159 - 165
[2] Journal of Organic Chemistry, 2011, vol. 76, # 21, p. 8726 - 8736
[3] Journal of Organic Chemistry, 1981, vol. 46, # 15, p. 3056 - 3060
[4] Chemistry - A European Journal, 2016, vol. 22, # 18, p. 6382 - 6388
[5] Dissertation <Berlin 1883>, S. 48,
[6] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 1394 - 1397[7] Zhurnal Obshchei Khimii, 1960, vol. 30, p. 1363 - 1366
[8] Patent: WO2014/151147, 2014, A1, . Location in patent: Paragraph 00514
[9] Patent: US2014/357651, 2014, A1, . Location in patent: Paragraph 0498
[10] Patent: US9174994, 2015, B2, . Location in patent: Page/Page column 126
4
[ 95-16-9 ]
[ 2942-06-5 ]
Reference：
[1] Patent: US5677321, 1997, A,
5
[ 95-16-9 ]
[ 2942-05-4 ]
[ 2942-08-7 ]
[ 2942-06-5 ]
Reference：
[1] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 1394 - 1397[2] Zhurnal Obshchei Khimii, 1960, vol. 30, p. 1363 - 1366
6
[ 95-16-9 ]
[ 2942-05-4 ]
[ 2942-06-5 ]
Reference：
[1] Journal of the Chemical Society, 1954, p. 2261,2262
[2] Yakugaku Zasshi, 1952, vol. 72, p. 1266[3] Chem.Abstr., 1953, p. 12357
[4] Yakugaku Zasshi, 1942, vol. 62, p. 47,51; dtsch. Ref. S. 19, 22[5] Chem.Abstr., 1951, p. 609
7
[ 95-16-9 ]
[ 2942-08-7 ]
[ 2942-06-5 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1949, p. 103,111
8
[ 95-16-9 ]
[ 615-20-3 ]
Yield
Reaction Conditions
Operation in experiment
88%
With tetrachloromethane; sodium t-butanolate In N,N-dimethyl-formamide at 20℃; for 3 h;
Benzothiazole (1 mmol, 135.9 mg),Carbon tetrachloride (1.1 mmol, 169.2 mg) was placed in a 10 mL round bottom flask.Add 5 mL of N,N-dimethylformamideSodium tert-butoxide (4.0 mmol, 384.4 mg),Stir at room temperature for 3 hours,TLC monitored the endpoint of the reaction.The mixture was poured into water and extracted with dichloromethane. The organic phase was collected and dried. The dichloromethane was removed by rotary evaporation to give the crude product.The crude product was subjected to silica gel column chromatography with petroleum ether and ethyl acetate as eluent (volume ratio = 30:1).2-Chlorobenzothiazole (brown oily liquid, 149.2 mg, yield 88percent) was obtained.
Reference：
[1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 6, p. 886 - 890
[2] Patent: CN107501023, 2017, A, . Location in patent: Paragraph 0063; 0064
[3] Organic Letters, 2009, vol. 11, # 2, p. 421 - 423
[4] Journal of Organic Chemistry, 2009, vol. 74, # 21, p. 8309 - 8313
[5] Chemische Berichte, 1880, vol. 13, p. 16
[6] Journal of Organometallic Chemistry, 1999, vol. 588, # 2, p. 155 - 159
[7] Journal of Organometallic Chemistry, 2000, vol. 601, # 2, p. 233 - 236
9
[ 136-95-8 ]
[ 67-66-3 ]
[ 95-16-9 ]
[ 615-20-3 ]
[ 34263-66-6 ]
[ 2602-85-9 ]
Reference：
[1] Journal of Chemical Research, Miniprint, 1980, # 12, p. 4935 - 4953
[2] Journal of Chemical Research, Miniprint, 1980, # 12, p. 4935 - 4953
10
[ 95-16-9 ]
[ 10026-13-8 ]
[ 615-20-3 ]
Reference：
[1] Chemische Berichte, 1880, vol. 13, p. 16
11
[ 95-16-9 ]
[ 2516-40-7 ]
Yield
Reaction Conditions
Operation in experiment
93%
With carbon tetrabromide; sodium t-butanolate In N,N-dimethyl-formamide at 20℃; for 3 h;
Benzothiazole (1 mmol, 135.9 mg),Carbon tetrabromide (1.1 mmol, 364.8 mg) was placed in a 10 mL round bottom flask.Added 5 mL of N,N-dimethylformamide and sodium tert-butoxide (4.0 mmol, 384.4 mg).Stir at room temperature for 3 hours,TLC monitored the endpoint of the reaction.The mixture was poured into water and extracted with dichloromethane. The organic phase was collected and dried. The dichloromethane was removed by rotary evaporation to give the crude product.The crude product was subjected to silica gel column chromatography with petroleum ether and ethyl acetate as eluent (volume ratio = 30:1).2-Bromobenzothiazole (light yellow oily liquid, 199 mg, yield 93percent) was obtained.
Reference：
[1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 6, p. 886 - 890
[2] Patent: CN107501023, 2017, A, . Location in patent: Paragraph 0051; 0052
[3] Organic Letters, 2009, vol. 11, # 2, p. 421 - 423
[4] Journal of Organic Chemistry, 2009, vol. 74, # 21, p. 8309 - 8313
[5] European Journal of Organic Chemistry, 2013, # 9, p. 1644 - 1648
[6] Journal of Organometallic Chemistry, 2000, vol. 601, # 2, p. 233 - 236
[7] Tetrahedron Letters, 2003, vol. 44, # 47, p. 8535 - 8537
[8] Recueil des Travaux Chimiques des Pays-Bas, 1937, vol. 56, p. 699,706
12
[ 95-16-9 ]
[ 533-30-2 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1949, p. 103,111
[2] Yakugaku Zasshi, 1942, vol. 62, p. 47,51; dtsch. Ref. S. 19, 22[3] Chem.Abstr., 1951, p. 609
[4] Journal of Organic Chemistry, 2011, vol. 76, # 21, p. 8726 - 8736
[5] Phytochemistry, 2012, vol. 74, p. 159 - 165
[6] Patent: WO2014/151147, 2014, A1,
[7] Patent: US2014/357651, 2014, A1,
[8] Patent: US9174994, 2015, B2,
Reference：
[1] Yakugaku Zasshi, 1942, vol. 62, p. 47,51; dtsch. Ref. S. 19, 22[2] Chem.Abstr., 1951, p. 609
[3] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 1394 - 1397[4] Zhurnal Obshchei Khimii, 1960, vol. 30, p. 1363 - 1366
15
[ 95-16-9 ]
[ 37859-43-1 ]
Reference：
[1] Chemical Communications, 2017, vol. 53, # 54, p. 7545 - 7548
16
[ 95-16-9 ]
[ 6285-57-0 ]
Reference：
[1] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 1394 - 1397[2] Zhurnal Obshchei Khimii, 1960, vol. 30, p. 1363 - 1366
[3] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 1394 - 1397[4] Zhurnal Obshchei Khimii, 1960, vol. 30, p. 1363 - 1366
17
[ 95-16-9 ]
[ 6973-51-9 ]
Reference：
[1] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 1394 - 1397[2] Zhurnal Obshchei Khimii, 1960, vol. 30, p. 1363 - 1366
18
[ 95-16-9 ]
[ 121-33-5 ]
[ 36341-25-0 ]
Yield
Reaction Conditions
Operation in experiment
46%
With silver(I) 4-methylbenzenesulfonate In water at 100℃; for 12 h; Sealed tube; Inert atmosphere; Green chemistry
General procedure: A sealed pressure vessel was charged with benzothiazole (68 mg, 0.5 mmol), AgOTs (280 mg, 1 mmol),aldehyde (0.6 mmol) and 2.0 mL of H2O. The resulting solution was stirred at 100 C for 12 h under N2.Upon completion of the reaction, H2O (8.0 mL) was added, then extracted with EtOAc (5 mL × 3), driedover Na2SO4, and concentrated under reduced pressure. The residue was further purified with flashcolumn chromatography.
Reference：
[1] Green Chemistry, 2012, vol. 14, # 6, p. 1577 - 1580
[2] Heterocycles, 2018, vol. 96, # 7, p. 1226 - 1237
19
[ 95-16-9 ]
[ 79-37-8 ]
[ 4464-60-2 ]
Reference：
[1] Justus Liebigs Annalen der Chemie, 1977, p. 159 - 168
With 1-iodo-2,2,3,3,4,4,5,5,5-nonafluorobutane; sodium t-butanolate In N,N-dimethyl-formamide at 20℃; for 0.333333 h;
Benzothiazole (1 mmol, 135.9 mg),Perfluoroiodobutane (1.1 mmol, 380.5 mg) was placed in a 10 mL round bottom flask.Add 5 mL of N,N-dimethylformamide and sodium tert-butoxide (0.5 mmol, 48.1 mg).Stir at room temperature for 20 minutes,TLC monitored the endpoint of the reaction.Pour the mixture into waterExtract with dichloromethane,The organic phase is collected, dried, and the dichloromethane is removed by rotary evaporation.Crude product.The crude product was subjected to silica gel column chromatography with petroleum ether and ethyl acetate as eluent (volume ratio = 30:1).2-Iodobenzothiazole (white solid, 257.6 mg, yield 99percent) was obtained.It can also be purified by recrystallization: The crude product is washed with cold water, filtered, and the product is dissolved in ethanol (2 mL).Heat to completely dissolve.Let stand, cool slowly and crystals precipitate.
67%
Stage #1: With 2,2,6,6-tetramethyl-piperidine; n-butyllithium; dichloro(N,N,N’,N‘-tetramethylethylenediamine)zinc In tetrahydrofuran; hexane at 0 - 20℃; for 2 h; Inert atmosphere Stage #2: With iodine In tetrahydrofuran; hexaneInert atmosphere
General procedure: To a stirred, cooled (0 °C) solution of 2,2,6,6-tetramethylpiperidine (0.25 mL, 1.5 mmol) in THF (2–3 mL) were successively added BuLi (about 1.6 M hexanes solution, 1.5 mmol) and, 5 min later, ZnCl2∘TMEDA14 (0.13 g, 0.50 mmol). The mixture was stirred for 15 min at 0 °C before introduction of the substrate (1.0 mmol) at 0–10 °C. After 2 h at room temperature, a solution of I2 (0.38 g,1.5 mmol) in THF (4 mL) was added. The mixture was stirred overnight before addition of an aqueous saturated solution of Na2S2O3(4 mL) and extraction with AcOEt (3 20 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. To the crude iodide were added Cs2CO3(0.65 g, 2.0 mmol), Cu powder (13 mg, 0.20 mmol), the azole (1.5 mmol) and MeCN (5 mL) and the resulting mixture was heated under reflux for 24 h. Filtration over Celite, washing with AcOEt,removal of the solvent and purification by chromatography on silica gel (the eluent is given in the product description) led to the compound described below.
55%
With 1,10-Phenanthroline; iodine; copper(ll) bromide; lithium tert-butoxide In 1,4-dioxane at 80℃; Inert atmosphere
General procedure: To a flame-dried reaction tube was added 1,3-azoles (0.5 mmol, 1.0 eq), 1,10-phenoline (0.5 mmol, 1.0 eq), LiOtBu (1.0 mmol, 2.0 eq), CuBr2 (0.10 mmol, 0.2 eq) and iodine (0.75 mmol, 1.5 eq). Dry 1,4-dioxane (2 mL) was added to the mixture and the mixture was heated to 80°C by putting the reaction tube to a preheated oil bath until the products were not increased. The mixture was cooled to room temperature and filtered through a short pad of silica gel. The silica gel was washed with EtOAc (20 mL) and the combined the organic phase was concentrated under reduced pressure to give a residue which was purified by silica gel column chromatography to afford the iodination product.
Reference：
[1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 6, p. 886 - 890
[2] Patent: CN107501023, 2017, A, . Location in patent: Paragraph 0033; 0034
[3] Angewandte Chemie - International Edition, 2006, vol. 45, # 18, p. 2958 - 2961
[4] Chemical Communications, 2008, # 42, p. 5375 - 5377
[5] Chemistry - A European Journal, 2009, vol. 15, # 39, p. 10280 - 10290
[6] Journal of the American Chemical Society, 2007, vol. 129, # 49, p. 15102 - 15103
[7] Journal of the American Chemical Society, 2007, vol. 129, # 7, p. 1921 - 1930
[8] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 13, p. 3498 - 3507
[9] Journal of the American Chemical Society, 2001, vol. 123, # 6, p. 1017 - 1022
[10] Tetrahedron Letters, 2015, vol. 56, # 3, p. 511 - 513
[11] Journal of Organic Chemistry, 2008, vol. 73, # 1, p. 177 - 183
[12] Chemistry - A European Journal, 2015, vol. 21, # 43, p. 15377 - 15387
[13] Arzneimittel-Forschung/Drug Research, 2000, vol. 50, # 11, p. 1023 - 1027
[14] Organic Letters, 2010, vol. 12, # 11, p. 2517 - 2519
[15] Journal of the American Chemical Society, 2011, vol. 133, # 34, p. 13577 - 13586
[16] Synthesis (Germany), 2013, vol. 45, # 7, p. 936 - 942
[17] Angewandte Chemie - International Edition, 2014, vol. 53, # 30, p. 7928 - 7932[18] Angew. Chem., 2014, vol. 126, # 30, p. 8062 - 8066,5
[19] Organometallics, 2016, vol. 35, # 6, p. 875 - 886
22
[ 95-16-9 ]
[ 6574-98-7 ]
[ 1123-99-5 ]
[ 1402247-75-9 ]
Reference：
[1] Angewandte Chemie - International Edition, 2014, vol. 53, # 30, p. 7928 - 7932[2] Angew. Chem., 2014, vol. 126, # 30, p. 8062 - 8066,5
23
[ 7144-49-2 ]
[ 95-16-9 ]
[ 20277-69-4 ]
Reference：
[1] Chemistry Letters, 1984, p. 2125 - 2128
24
[ 95-16-9 ]
[ 4214-28-2 ]
[ 1019453-85-0 ]
Yield
Reaction Conditions
Operation in experiment
78.3%
With iron(III) chloride; sodium hydroxide; trans-1,2-cyclohexanediamine In water at 110℃; for 4 h; Inert atmosphere
FeCl3 (3.2 g, 0.2 eq) under nitrogen atmosphere,Trans-1,2-cyclohexanediamine (5.6g, 0.4eq),Benzothiazole (13.5g),2,4-Dimethyl iodobenzene (34.5 g) NaOH (12 g, 3 eq),And 100 mL of water in a 250 mL round bottom flask,Reacted at 110 ° C for 4 hours,After the reaction was completed, it was extracted with ethyl acetate and dried.Column chromatography gave 18 g of the desired product.The yield was 78.3percent.
Reference：
[1] Patent: CN107266390, 2017, A, . Location in patent: Paragraph 0021; 0022
25
[ 95-16-9 ]
[ 654070-00-5 ]
Reference：
[1] Journal of Organic Chemistry, 2011, vol. 76, # 21, p. 8726 - 8736
With carbon tetrabromide; sodium t-butanolate; In N,N-dimethyl-formamide; at 20℃; for 3h;
Benzothiazole (1 mmol, 135.9 mg),Carbon tetrabromide (1.1 mmol, 364.8 mg) was placed in a 10 mL round bottom flask.Added 5 mL of N,N-dimethylformamide and sodium tert-butoxide (4.0 mmol, 384.4 mg).Stir at room temperature for 3 hours,TLC monitored the endpoint of the reaction.The mixture was poured into water and extracted with dichloromethane. The organic phase was collected and dried. The dichloromethane was removed by rotary evaporation to give the crude product.The crude product was subjected to silica gel column chromatography with petroleum ether and ethyl acetate as eluent (volume ratio = 30:1).2-Bromobenzothiazole (light yellow oily liquid, 199 mg, yield 93percent) was obtained.
A compound of Formula O-l is treated with, for example, nitric acid to produce a compound of Formula 0-2. The compound of Formula 0-2 is treated with a reducing agent such as stannous chloride to produce a compound of Formula 0-3. The compound of 0-3 is treated with sodium nitrate in acid and cupric bromide to produce a compound of Formula 0-4. The compound of 0-4 is treated a base such as butyl lithium and boron tris-isopropoxide to produce a compound of Formula 0-5.
With 1-iodo-2,2,3,3,4,4,5,5,5-nonafluorobutane; sodium t-butanolate; In N,N-dimethyl-formamide; at 20℃; for 0.333333h;
Benzothiazole (1 mmol, 135.9 mg),Perfluoroiodobutane (1.1 mmol, 380.5 mg) was placed in a 10 mL round bottom flask.Add 5 mL of N,N-dimethylformamide and sodium tert-butoxide (0.5 mmol, 48.1 mg).Stir at room temperature for 20 minutes,TLC monitored the endpoint of the reaction.Pour the mixture into waterExtract with dichloromethane,The organic phase is collected, dried, and the dichloromethane is removed by rotary evaporation.Crude product.The crude product was subjected to silica gel column chromatography with petroleum ether and ethyl acetate as eluent (volume ratio = 30:1).2-Iodobenzothiazole (white solid, 257.6 mg, yield 99%) was obtained.It can also be purified by recrystallization: The crude product is washed with cold water, filtered, and the product is dissolved in ethanol (2 mL).Heat to completely dissolve.Let stand, cool slowly and crystals precipitate.
67%
General procedure: To a stirred, cooled (0 C) solution of 2,2,6,6-tetramethylpiperidine (0.25 mL, 1.5 mmol) in THF (2-3 mL) were successively added BuLi (about 1.6 M hexanes solution, 1.5 mmol) and, 5 min later, ZnCl2?TMEDA14 (0.13 g, 0.50 mmol). The mixture was stirred for 15 min at 0 C before introduction of the substrate (1.0 mmol) at 0-10 C. After 2 h at room temperature, a solution of I2 (0.38 g,1.5 mmol) in THF (4 mL) was added. The mixture was stirred overnight before addition of an aqueous saturated solution of Na2S2O3(4 mL) and extraction with AcOEt (3 20 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. To the crude iodide were added Cs2CO3(0.65 g, 2.0 mmol), Cu powder (13 mg, 0.20 mmol), the azole (1.5 mmol) and MeCN (5 mL) and the resulting mixture was heated under reflux for 24 h. Filtration over Celite, washing with AcOEt,removal of the solvent and purification by chromatography on silica gel (the eluent is given in the product description) led to the compound described below.
55%
With 1,10-Phenanthroline; iodine; copper(ll) bromide; lithium tert-butoxide; In 1,4-dioxane; at 80℃;Inert atmosphere;
General procedure: To a flame-dried reaction tube was added 1,3-azoles (0.5 mmol, 1.0 eq), 1,10-phenoline (0.5 mmol, 1.0 eq), LiOtBu (1.0 mmol, 2.0 eq), CuBr2 (0.10 mmol, 0.2 eq) and iodine (0.75 mmol, 1.5 eq). Dry 1,4-dioxane (2 mL) was added to the mixture and the mixture was heated to 80C by putting the reaction tube to a preheated oil bath until the products were not increased. The mixture was cooled to room temperature and filtered through a short pad of silica gel. The silica gel was washed with EtOAc (20 mL) and the combined the organic phase was concentrated under reduced pressure to give a residue which was purified by silica gel column chromatography to afford the iodination product.
6-Nitrobenzothiazole To a 30 mL solution of 1:1 mixture of HNO3 --H2 SO4 was added benzothiazole (7.0 mL, 53 mmol) slowly over 1 h period at -25 C. and resulting solution was stirred for 12 h. Reaction temperature was allowed to warm up to 25 C. The reaction mixture was poured into ice water to produce a yellow precipitation which was subjected to column chromatography (CHCl3, neat) to yield 7.3 g (41 mmol, 79%) of the desired product.
EXAMPLE 44 Benzothiazole-2-carboxylic Acid A precooled (-78 C.) solution of 7.7 ml (19.2 mmol) of n-butyllithium in 50 ml of dry tetrahydrofuran was treated dropwise with 2.0 ml (18.3 mmol) of benzothiazole. After the addition was complete, the solution was poured into a mixture of excess dry ice in 100 ml of tetrahydrofuran. After being allowed to warm, the resulting solution was treated with water, washed with ether, acidified with HCl, and filtered to give a yellow solid. Digestion with boiling ether followed by filtration gave 1.55 g (47%) of the desired compound as a nearly white solid.
1,3,5-tris(o-aminophenylthiomethyl)mesitylene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydroxide; In water; toluene;
EXAMPLE 1 Preparation of 2,4,6-tris(o-aminophenylthiomethyl)mesitylene A 2-liter glass reaction vessel equipped with a Teflon stirrer, reflux condenser, addition funnel, 2-thermometers and an electrical heater was charged with 243 g water and 104.2 g sodium hydroxide pellets. After boiling under a nitrogen atmosphere for 5 minutes, 167.8 g benzothiazole was gradually added to the contents of the reactor over 50 minutes. The resultant mixture was then heated at the boiling point for 2 hours. A solution of 0.5 g tetrabutyl phosphonium chloride (50% in toluene) and 50 g toluene was then added, which cooled the reaction mixture to 90 C. A solution of 100 g 2,4,6-tris(chloromethyl)mesitylene in 300 g of warm toluene was added over a 15 minute period and the resultant mixture was heated at the boiling point for 2 hours. The aqueous phase of the reaction mixture was then removed and the organic phase washed with 100 g hot water. The residual water was removed by azeotropic distillation. After being filtered the toluene solution gradually cooled to room temperature, during which time a slightly off-white solid crystallized. The solid was filtered off, washed sequentially with cold toluene and heptane and then dried under reduced pressure at 90 C. The product weighed 164.7 g melted from 161 to 166 C. and exhibited an amine equivalent of 181. The theoretical amine equivalent for the expected product, 1,3,5-tris(o-aminophenylthiomethyl)mesitylene is 178.
2-(2-methoxypyrimidin-5-yl)-1,3-benzothiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With caesium carbonate; copper(I) bromide;bis(tri-t-butylphosphine)palladium(0); In N,N-dimethyl-formamide; at 150℃; for 1h;
To 1,3-benzothiazole (0.100 g, 0.74 mmol) in dry DMF (3.5 mL) were added 5-bromo-2- methoxypyrimidine (0.168 g, 0.89 mmol), Cu(I)Br (23 mg, 0.16 mmol), cesium carbonate (0.242 g, 0.74 mmol) and bis(tri-t-butylphosphine) palladium (0) (38 mg, 0.075 mmol) and the reaction was heated in a sealed tube under argon at 150C for Ih. Water and dichloromethane were added and the layers separated. The aqueous layer was extracted with dichloromethane (3x). The combined organic phases were washed with water and brine, dried (MgSO4), filtered and the solvent was removed in vacuo. The crude material was purified by flash chromatography (Heptane/EtOAc 1 : 1) to give the title compound (71 mg) as a pale brown solid. 1H NMR delta ppm 9.26 (s, 2 H) 8.20 (d, 1 H) 8.09 (d, 1 H) 7.55-7.61 (m, 1 H) 7.46-7.53 (m, 1 H) 4.04 (s, 3 H); MS m/z (M+H) 244.
With tetra(n-butyl)ammonium hydroxide; water; copper(l) chloride; at 50℃; for 12h;Inert atmosphere;
General procedure: After standard cycles of evacuation and back-filling with dry and pure argon, an oven-dried Schlenk tube equipped with a magnetic stirring bar was charged with CuCl (5 molpercent), the aryl iodides if a solid (1.2 equiv). The tube was evacuated and backfilled with argon (this procedure was repeated three times). Under a counter flow of argon, benzothiazole (0.5 mmol), aryl iodides if a liquid (1.2 equiv) and degassed 40percent tetra-n-butylammonium hydroxides water solution (1.0 mL, 3.0 equiv) were added by syringe. The tube was sealed and the mixture was allowed to stir at 50 oC for 12 h. The reaction mixture was then allowed to cool to ambient temperature. Then, the mixture was quenched by the addition of a saturated NH4Cl solution (1.5 mL) and extracted with ethyl acetate (3.x.10 mL). Organic layers were gathered, dried over Na2SO4, filtered and concentrated in vacuum to yield the crude product. The obtained crude was purified by column chromatography on silica gel and the product was dried under vacuum for at least 0.5 h.
General procedure: n-BuLi (1.67 M solution in hexane, 1.32 mL, 2.2 mmol) was added dropwise into a solution of p-bromochlorobenzene (383 mg, 2.0 mmol) in THF (3 mL) at -78 C for 30 min. Then, ethyl formate (1.6 mL, 20 mmol) was added to the mixture and the obtained mixture was stirred at -78 C. After 3 h at the same temperature, I2 (1523 mg, 6 mmol), K2CO3 (1382 mg, 10 mmol) and EtOH (3 mL) were added at -78 C and the mixture was stirred for 14 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (5 mL) and was extracted with CHCl3 (3×20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide ethyl 4-chlorobenzoate in 77% yield. If necessary, the product was purified by short column chromatography (SiO2:hexane:EtOAc=9:1) to give pure ethyl 4-chloro-1-benzoate as a colorless oil.
SYNTHESIS EXAMPLE 5Preparation of 2-[(3-chloro-4-pyridinyl)fluoromethyl]benzothiazole (compound number 4) Step A: Preparation of a-(3-chloro-4-pyridinyl)-2-benzothiazolemethanolTo a stirred solution of benzothiazole (780 mg, 5.78 mmol) in tetrahydrofuran (25 mL) was added w-butyllithium (3.6 mL, 2.0 M in hexanes) dropwise at -78 C. After stirring at -78 C for 0.5 hr, a solution of <strong>[72990-37-5]3-chloro-4-pyridinecarboxaldehyde</strong> (900 mg, 6.36 mmol) in tetrahydrofuran (5 mL) was added slowly at -78 C to the reaction mixture. The reaction mixture was stirred for another 5 hrs at -78 C, then was treated with water and extracted with ethyl acetate. The combined organic phases were washed with water and saturated aqueous NaCl solution, dried with anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel using hexanes/ethyl acetate (60:40 to 10:90) as eluent to afford the title product as a pale yellow solid (120 mg)..H NMR (CDCI3) delta 8.62 (s, 1H), 8.55 (d, 1H), 8.06 (d, 1H), 7.88 (d, 1H), 7.60 (d, 1H), 7.24 (m, 2H), 6.32 (s, 1H).
With dipotassium peroxodisulfate; iron(III) chloride hexahydrate; In water; dimethyl sulfoxide; at 100℃; for 12h;
General procedure: A dried reflux tube equipped witha magnetic stir bar charged with benzothiazole derivative (0.5 mmol 1.0equiv), benzylalcohol derivative (1.5mmol 3.0equiv), FeCl3·6H2O (0.1equiv), K2S2O8 (2.0 equiv), DMSO/H2O (2:1 mL) and the reaction vessel was placedin a 100C oil bath for 12 h under air. After cooling to room temperature,the mixture was diluted with ethyl acetate and directly filtered through a padof celite and washed with water. The organic phase was dried over NaSO4and removed under reduced vacuum. The residue was purified by columnchromatography eluting with ethyl acetate and hexane to afford thedesired product.
With sodium tetrahydroborate; N,N,N,N,-tetramethylethylenediamine; palladium diacetate; triphenylphosphine; In tetrahydrofuran; at 60℃; for 24h;Inert atmosphere;
General procedure: Pd(OAc)2-PPh3, Pd2(dba)3-tbpf, Pd2(dba)3-DavePhos Pd2(dba)3-P(t-Bu)3 Pd2(dba)3-XantPhos and Pd(OAc)2-XPhos. Anhydrous THF (13.2 mL) was degassed by bubbling argon for few minutes, then Pd(OAc)2 (7.2 mg, 0.033 mmol, 5 mol%) and PPh3 (17.7 mg, 1.132 mmol, 20 mol%) were added and the resulting mixture stirred at room temperature for 30 min. The halogenated heterocycle (0.66 mmol), TMEDA (0.130 g, 1.12 mmol, 1.7 equiv) and finally NaBH4 (42.4 mg, 1.12 mmol, 1.7 equiv) were introduced in sequence. The mixture was stirred at room temperature or heated at 65 C under argon for the proper time. The residue was taken up in brine and extracted with ethyl acetate. The organic phase was separated, dried, the solvent was evaporated and the residue was purified by flash chromatography (mixtures of petroleum ether and ethyl acetate) to give pure hydrodehalogenated heterocycles
With potassium carbonate; In dimethyl sulfoxide; at 120℃; for 6h;Green chemistry;
General procedure: Benzothiazole (1.0 mmol), iodobenzene (1 mmol), 2 mmol K2CO3 and 5 mol% of nano CeO2-Fe3O4 catalyst were added in DMSO (1 mL) and the reaction was carried at 120 C for 5h. The progress of the reaction was monitored by Gas Chromatography (GC). After completion of reaction, the reaction mixture was cooled to room temperature and it was extracted with ethyl acetate dried over Na2SO4. The solvent was evaporated under reduced pressure to obtain product. The catalyst was easily recovered by magnetic separation followed by washing with ethanol and drying and preserved for next runs. The pure products were obtained by column chromatography using hexane: ethyl acetate as the eluent. The preserved catalyst reused in a subsequent run for recyclability study. The conversion of reactant was determined by Gas chromatography (GC).
With potassium phosphate; C11H16N2O2; copper(l) chloride; at 80℃; for 15h;Sealed tube;
The 540mg (4mmol) benzothiazole, 1780mg (6mmol) 2- bromo-1-iodo-4-methylphenyl, 64mg (0.4mmol) CuCl, 332mg (1.6mmol) ligand L3,1696mg (8mmol) K3PO4, 8gPEG-200, was added 30mL reaction tube, sealed, under the reaction condition of 80 15h.After the reaction is stopped, extracted with ethyl acetate, washed with water, brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated under reduced pressure, purified by silica gel column chromatography separation and purification, to give 2-methyl-phenothiazine 724mg, income rate of 85%.
With dipotassium peroxodisulfate; eosin y; at 20℃; for 20h;Schlenk technique; Irradiation;
Weigh benzothiazole (0.5 mmol), K2S2O8 (3 eq.) and Eosin Y (1.2 mol%) in a 25 mL Schlenk reaction tube and addN,N-dimethylpropanamide (7.676 g, 76 mmol), under air,The reaction was carried out under a 20 W LED white light, and the reaction was stirred at room temperature.Monitoring by TLC, the reaction was completed after 20 h, and the solvent was removed.The concentrate was separated by column chromatography (petroleum ether / ethyl acetate = 3: 1, V/V)A yellow oil is obtained, ie the derivative Ik. Yield 76%
76%
With dipotassium peroxodisulfate; eosin y; at 20℃; for 20h;Schlenk technique; Irradiation;
Benzothiazole (0.5 mmol), K2S2O8 (3 eq.) and Eosin Y (1.2 mol%) were weighed into a 25 mL Schlenk reaction tube, followed by N,N-dimethylpropanamide (7.676 g, 76 mmol). Under the air condition, the reaction was carried out under a 20 W LED white light. The reaction was stirred at room temperature and monitored by TLC. After 20 h, the reaction was completed. The reaction solution was concentrated to remove solvent and concentrated.The liquid was separated by column chromatography (petrole ether / ethyl acetate = 3:1, V/V) to give a yellow oil, the derivative Ie. The yield was 76%.
66%
With dipotassium peroxodisulfate; Eosin Y; at 20℃; for 24h;Schlenk technique;
Weigh benzothiazole (0.5mmol, 67mg), K2S2O8 (2mmol, 0.54g) and Eosin Y (0.01mmol, 6.5mg) in a 25mL Schlenk reaction tube, and then add N, N-dimethylpropionamide (38mmol, 3.8g), placed under a 20W LED white light to react, stirred the reaction at room temperature, followed by TLC to monitor the progress of the reaction, the reaction was completed after 24 hours, the reaction solution was concentrated to remove the solvent, and the concentrated solution was separated by column chromatography (eluent Petroleum ether / ethyl acetate) in a volume ratio of 5: 1) to give a yellow oil, the derivative Ik. The yield was 66%.
With 3'-((1H-benzo[d]imidazol-2-yl)amino)-4'-(4-methoxyphenyl)-4'hspiro[indene-2,5'-isoxazole]-1,3-dione; nickel diacetate; lithium tert-butoxide; In tetrahydrofuran; for 24h;Reflux;
General procedure: A 10 mL round-bottomed flask was charged with benzothiazole (19; 135 mg, 1 mmol), arylbenzene 18 (1 mmol), 14b (52.56 mg, 12 mol%), Ni(OAc)2 (17.68 mg, 10 mol%), t-BuOLi (160 mg, 2 mmol) and anhyd THF (5 mL). The mixture was stirred at reflux conditions for 24 h (TLC). The mixture was cooled to r.t. and the solvent was evaporated under reduced pressure. The mixture was diluted with EtOAc (10 mL) and successively washed with H2O and brine. The organic layer was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by preparative TLC eluting with EtOAc/hexane (20:80, v/v) to afford the corresponding product 20.
To a slurry of N,N'-carbonyldiimidazole (1 mmol, 162 mg) in THF (1 ml) was added a solution of benzoic acid (1 mmol, 122 mg) in THF (3 ml). The reaction mixture was stirred at room temperature for 1 h, and the resulting v solution was then concentrated to approximately 1 ml in vacuo. In a separate reaction vessel was added a solution of benzothiazole (1.2 mmol, 162 mg) in THF (1 mL) to a solution of i-PrMgCl·LiCl (1 ml, 1.3M in THF, 1.3 mmol) in THF (8 mL) over 3 min, maintaining an internal temperature at -10 C. The homogeneous solution was then stirred for 30 min. After this hold time, the (1H-imidazol-1-yl)(phenyl)methanone solution was added dropwise, and the resulting dark reddish solution was warmed to room temperature and stirred for 3 h. The reaction was quenched by addition of 13.5% NH4Cl aqueous solution (1.5 mL). The layers were mixed and then separated, and the aqueous layer was extracted with dichloromethane (3 × 10 mL). The combined organics were dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by silica column chromatography to afford the product 2a as a yellow solid (215 mg, 90%).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
HazMat Fee +
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
