5-Chloro-2-mercaptobenzoxazole

To a stirred solution of 2-amino-4-chlorophenol (20.0 g, 139.3 mmol) in EtOH (500 mL) was added KOH (18.36 g, 327.3 mmol) followed by CSCompound 19:Potassium ethyl xanthate (535.8 g, 3.343 mol)Was slowly added to a solution of 2-amino-4-chlorophenol (400 g, 2.786 mol)In ethanol (3 L)And stirred at room temperature for 10 minutes, then slowly raised to 80 ° C until the reaction was complete.Point plate found that the raw material points disappeared, the reaction mixture into the ice water (7L) with acetic acid neutralization to neutral.Filter, filter residue with 5L ice water, 2L n-hexane, and dried under reduced pressure to give a white solid (512.5 g, 99.1percent) of 5-chloro-2-mercaptobenzoxazole.Potassium ethylxanthate (893.2 g, 5.572 moles) was added to a stirred mixture of 2-Amino-4-Chloro phenol (400 g, 2.786 moles) and Ethanol (3 liter) at room temperature and stirred for 10 minutes. A mixture of 2-amino-4-chlorophenol (100 g, 0.69 mol) Potassium ethyl xanthate (13.3 g, 0.83 mol) and 1500 ml of absolute ethanol were added to a 3 L four-necked reaction flask, Heated to reflux for 8 hours. The ethanol was distilled off under reduced pressure, The residue was dissolved in 1300 ml of water, Acidified with 100 ml of concentrated hydrochloric acid and filtered to give 122.6 g of a white solid, Yield 94.9percentStep 5) Synthesis of 5-chlorobenzo [d] oxazole-2-thiolTo ethanol (100 mL) were added sequentially 2-amino-4-chlorophenol (6.02 g, 41.94 mmol) and ehtyl potassium xanthate (7.07 g, 44.09 mmol) , the reaction was heated gradually to reflux and stirred for 7 hours, and then concentrated in vacuo. The thick oil was dissolved in water (150 mL) , and extracted with ethyl acetate (100 mL) . The aqueous layer was adjusted to pH 4 to 5 with aqueous hydrochloric acid solution (1 M) , and white solid precipitated out. Filtered under vacuum, the solid was dried to give the title compound as a white solid (7.02 g, 90.2 percent) .MS (ESI, pos. ion) m/z: 186.1 [M+H] +; and1H NMR (DMSO-d6, 600 MHz) d (ppm) : 13.99 (s, 1H) , 7.52 (d, J = 8.2 Hz, 1H) , 7.31-7.28 (m, 2H)Step 12-amino-4-chlorophenol 1.0 g (7 mmol) and 1.34 g (8.4 mmol) of potassiumO-ethylxanthate were dissolved in 20 ml of ethanol in a dried round flask provided with nitrogen gas, followed refluxing the mixture with stirring for 16 hrs. The resulting solution was concentrated under a reduced pressure, mixed with ethylacetate, and washed with water. The formed organic layer was washed with a sodium hydrogen carbonate solution and a saturated NaCl solution, dried over anhydrous magnesium sulfate, and distilled under a reduced pressure. The resulting residue was subjected to silica gel column chromatography (dichloromethane:methanol=49:l) to obtain 5-chloro-2-thiobenzooxazole(yield: 57percent).General procedure: 2-Aminophenol (1.0 mmol), K2CO3 (3.0 mmol) was dissolved in DMF (3 mL) in a dried tube, equipped with a magnetic stirring bar and a septum. The mixture was stirred for 5 minutes, and then TMTD (0.6 mmol) was added. The reaction mixture was then heated at 120 °C and checked by TLC until the starting material was finished (around 12 hours). The reaction was cooled down to room temperature, and then quenched with sat. NH4Cl solution and extracted with ethyl acetate, dried over anhydrous Na2SO4 and evaporated under vacuum. The residue was purified by flash column chromatography to afford the desired product.153.57 mg (1 mmol) of 5-chlorobenzoxazole, 216 μL (2.0 mmol) of 1, 3-propanedithiol, 280.55 mg (5.0 mmol) of potassium hydroxide and 3 mL of DMSO were placed in a reaction equipped with a magnetic stir bar. The tube was sealed with argon, heated and stirred, and reacted in an oil bath at 130 ° C for 24 hours. After the reaction is completed, the reaction solution is transferred to a separating funnel with water washing, an appropriate amount of dilute hydrochloric acid is added, the aqueous phase is adjusted to pH 1-3, and the organic phase is extracted with ethyl acetate, and the upper organic phase is transferred with anhydrous magnesium sulfate. The mixture was dried under reduced pressure and purified by column chromatography to yield 113.2mg of product as a red-brown solid, yield 73.7percent.2-Amino-4-chlorophenol (2.50 kg, 17.4 mol) was charged to a vessel and suspended in water (52 L) and methanol (10.4L). High dilution was required to prevent slow and difficult filtration of the product. The mixture was stirred, cooled to 0° C., then thiophosgene (2.00 kg, 17.4 mol) was added to the suspension ensuring that the internal temperature remained at 5° C. throughout the addition. Water (8 L) andmethanol (2 L) were added to aid stirring and the slurry was warmed to 13° C. for 1 h, followed by aging at 20° C. for a thrther 1 h. The slurry was then filtered and the solid washed with water (5 L). The batch was repeated and combined to dry in a vacuum oven (T=40° C.) for 15 h togive 9-a (5.81 kg, 31.3 mol). The data corresponds to the commercially available material. ‘H NMR (400 MHz, d5-DMSO): ö 7.51 (d, 1H, J=9.2 Hz), 7.30726 (m, 2H). ‘3C NMR (100.6 MHz, d5-DMSO): ö 181.2, 147.4, 133.1, 129.7, 123.9, 111.6, 110.8. HRMS (ESI): m/z [M+H] calcd for C7H4C1NOS: 185.9780; found: 185.9785.General procedure: A mixture of intermediate compound N-(3-(1H-tetrazole-5-yl) phenyl)-2-chloroacetamideand benzo[d]oxazole-2-thiol or benzo[d]thiazole-2-thiol or 2-mercapto benzimidazoles in anequimolar amount were taken and refluxed with acetone (20 mL) in the presence of K2CO3for 24 hr. The reaction was monitored by TLC and on completion of the reaction, an excessof solvent was evaporated at room temperature and the reaction mixture was diluted withwater (about 200 mL). The diluted hydrochloric acid was added to precipitate the productwhich was further filtered and thoroughly washed with cold water.General procedure: Commercially available 5-chloro-2-mercapto benzoxazole or benzothiazole (10 mmol) and K2CO3 (15mmol) were added to 50 mL of acetone. After 10 min, appropriate 1-bromo--bromoalkane (12 mmol) was added and the mixture was stirred at room temperature for 24 h. After this time the suspension was filtered from inorganic material and the solvent was evaporated under reduced pressure. The residue was suspended in water and extracted with diethyl ether (3 × 50 mL). The combined extracts were washed with water, dried over anhydrous Na2SO4, and evaporated under reduced pressure to givein termediates 9-12 that were used without further purification for the final step. For analytical purpose, a little amount was purified by means of flash chromatography, using cyclohexane/ethyl acetate 9.5:0.5v/v as eluent. Analytical and spectral data are reported for novel compounds 9-12General procedure: Commercially available 5-chloro-2-mercapto benzoxazole or benzothiazole (10 mmol) and K2CO3 (15mmol) were added to 50 mL of acetone. After 10 min, appropriate 1-bromo--bromoalkane (12 mmol) was added and the mixture was stirred at room temperature for 24 h. After this time the suspension was filtered from inorganic material and the solvent was evaporated under reduced pressure. The residue was suspended in water and extracted with diethyl ether (3 × 50 mL). The combined extracts were washed with water, dried over anhydrous Na2SO4, and evaporated under reduced pressure to givein termediates 9-12 that were used without further purification for the final step. For analytical purpose, a little amount was purified by means of flash chromatography, using cyclohexane/ethyl acetate 9.5:0.5v/v as eluent. Analytical and spectral data are reported for novel compounds 9-12. 2-[(3-Bromopropyl)thio]-5-chlorobenzo[d]oxazole (9)The title compound was obtained as pink oil (96%); 1H NMR (500 MHz, DMSO-d6): delta7.76 (d, J = 1.9Hz, 1H, benzoxazole), 7.68 (d, J = 8.5 Hz, 1H, benzoxazole), 7.36 (dd, J = 8.5, 1.9 Hz, 1H, benzoxazole), 3.66 (t, J = 6.5 Hz, 2H, CH2Br), 3.44 (t, J = 7.0 Hz 2H, SCH2), 2.37-2.32 (m, 2H, CH2CH2CH2). 13C NMR (125 MHz, DMSO-d6): delta165.99, 150.02, 142.50, 128.86, 124.14, 117.98, 111.41, 32.72, 31.61, 30.26. Anal. (C10H9BrClNOS) C, H, N, S.

Molecular Weight:185.63
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:184.9702126
Monoisotopic Mass:184.9702126
Topological Polar Surface Area:53.4
Heavy Atom Count:11
Complexity:187
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes