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With potassium hydroxide In methanol for 9 h; Reflux
KOH (0.83 g) was added to a solution of compound 4 (1 g) in anhydrous methanol (15 mL) and refluxed for 9 h. After reaction, the solution was neutralised to pH 5 and poured into cool water (100 mL). The residue was filtered and dried to obtain compound 5 as a white solid: yield:85percent; m.p. 157–159 °C; 1H NMR (500 MHz, CDCl3): δ 8.20 (s, 1H),7.93 (d, J = 8.7 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 3.88 (s, 3H); 13C NMR(126 MHz, CDCl3): δ 169.0, 162.3, 162.0, 146.5, 128.5, 126.8, 125.1,114.5, 55.5. HRMS (ESI) m/z calcd for C11H9NNaO3S [M + Na]+:258.0195; found: 258.0202.
Reference：
[1] Journal of Chemical Research, 2018, vol. 42, # 7, p. 366 - 370
[2] Justus Liebigs Annalen der Chemie, 1975, p. 1618 - 1624
2
[ 67-56-1 ]
[ 57677-79-9 ]
[ 57677-80-2 ]
Reference：
[1] Journal of Molecular Structure, 2018, vol. 1173, p. 81 - 91
3
[ 1332708-68-5 ]
[ 57677-79-9 ]
Yield
Reaction Conditions
Operation in experiment
83%
With oxygen; copper diacetate In N,N-dimethyl-formamide at 120℃; for 20 h; Molecular sieve
General procedure: To a solution of 4-carboxythiazoline or 4-carboxyoxazoline (0.5 mmol) in anhydrous DMF (1 mL) were added molecular sieves (4 Å, 100percent wt) and Cu(OAc)2 (9.1 mg, 0.05 mmol). The reaction mixture was stirred with an O2 balloon at 120 °C for 10-24 h. The resulting mixture was diluted with ethyl acetate and the solution was washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to afford 4-carboxythiazole or 4-carboxyoxazole.
With potassium carbonate In N,N-dimethyl-formamide at 40℃; for 8 h;
Compound 3 (1.00 g, 4.02 mmol) was combined with methyl iodide(8.04 mmol), K2CO3 (1.11 g, 8.04 mmol) and DMF (8 mL). The reaction mixture was heat to 40 °C for 8 h. The reaction mixture was cooled and DMF was evaporated under reduced pressure. The residue was extracted with ethyl acetate (50 mL), filtered and evaporatedunder reduced pressure to yield the crude product, which was purifiedby column chromatography using petroleum ether and ethyl acetate(4:1) as an eluent to obtain compound 4 as a white solid: yield 89percent;m.p. 93–95 °C ; 1H NMR (500 MHz, CDCl3): δ 8.11 (s, 1H), 7.97 (d,J = 8.6 Hz, 2H), 6.98 (d, J = 8.6 Hz, 2H), 4.47 (q, J = 7.1 Hz, 2H), 3.89 (s, 3H), 1.45 (t, J = 7.1 Hz, 3H); 13C NMR (126 MHz, CDCl3): δ168.8, 161.63, 161.56, 147.9, 128.5, 126.2, 125.8, 114.3, 61.5, 55.4, 14.4.HRMS (ESI) m/z calcd for C13H13NNaO3S [M + Na]+: 286.0508; found:286.0521.
Reference：
[1] Journal of Chemical Research, 2018, vol. 42, # 7, p. 366 - 370
[2] Journal of Molecular Structure, 2018, vol. 1173, p. 81 - 91
With potassium hydroxide; In methanol; for 9.0h;Reflux;
KOH (0.83 g) was added to a solution of compound 4 (1 g) in anhydrous methanol (15 mL) and refluxed for 9 h. After reaction, the solution was neutralised to pH 5 and poured into cool water (100 mL). The residue was filtered and dried to obtain compound 5 as a white solid: yield:85%; m.p. 157-159 C; 1H NMR (500 MHz, CDCl3): delta 8.20 (s, 1H),7.93 (d, J = 8.7 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 3.88 (s, 3H); 13C NMR(126 MHz, CDCl3): delta 169.0, 162.3, 162.0, 146.5, 128.5, 126.8, 125.1,114.5, 55.5. HRMS (ESI) m/z calcd for C11H9NNaO3S [M + Na]+:258.0195; found: 258.0202.
With potassium phosphate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 100.0℃; for 15.0h;
Step 1 - Synthesis of2-(4-Methoxy-phenyl)-thiazole-4-carboxylic acid ethyl ester 2-Bromo-thiazole-4-carboxylic acid ethyl ester (1.00 mmol, 236 mg), 4- methoxyphenylboronic acid (1.50 mmol, 228 mg), Pd2(DBA)3 (0.020 mmol, 18 mg), S-Phos (0.060 mmol, 25 mg) and potassium phosphate tribasic monohydrate (1.5 mmol, 0.35 g) were loaded into a Schlenk tube containing a stir bar. The Schlenk tube was capped with a rubber septum, evacuated and refilled with nitrogen. Toluene (2 ml_) was added through the septum via a syringe and the Schlenk tube was sealed with a Teflon screw cap under a flow of nitrogen, and put into an oil bath at 100 0C. The reaction was allowed to stir at 1000C for 15 hours, then the reaction mixture was cooled to room temperature and filtered through celite. The filtrate was concentrated in vacuo and the resultant crude residue was purified using column chromatography on silica gel (eluent: Hexane/EtOAc (4:1 )) to provide 2-(4-Methoxy- phenyl)-thiazole-4-carboxylic acid ethyl ester as a yellowish solid.
Step 2 - Synthesis of2-(4-Methoxy-phenyl)-thiazole-4-carboxylic acidA mixture of 2-(4-Methoxy-phenyl)-thiazole-4-carboxylic acid ethyl ester and lithium hydroxide monohydrate (2.0 mmol, 84 mg) was diluted with a 2:1 mixture of THF:H2O (6 ml_), and the resulting reaction was allowed to stir at room temperature for about 15 hours. The reaction mixture was then acidified using aqueous HCI (1 M, 10 ml_), then dried via lyophilization to provide 2-(4-Methoxy-phenyl)-thiazole-4- carboxylic acid as an ammonium chloride salt. HPLC-MS RT= 1.37 minutes; mass calculated for formula CnH9NO3S 235.03, observed LCMS m/z 236.10 (M+H).
With oxygen; copper diacetate; In N,N-dimethyl-formamide; at 120.0℃; under 760.051 Torr; for 20.0h;Molecular sieve;
General procedure: To a solution of 4-carboxythiazoline or 4-carboxyoxazoline (0.5 mmol) in anhydrous DMF (1 mL) were added molecular sieves (4 A, 100% wt) and Cu(OAc)2 (9.1 mg, 0.05 mmol). The reaction mixture was stirred with an O2 balloon at 120 C for 10-24 h. The resulting mixture was diluted with ethyl acetate and the solution was washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to afford 4-carboxythiazole or 4-carboxyoxazole.
ethyl 2-(4-hydroxyphenyl)thiazole-4-carboxylate[ No CAS ]
[ 74-88-4 ]
[ 57677-79-9 ]
Yield
Reaction Conditions
Operation in experiment
89%
With potassium carbonate; In N,N-dimethyl-formamide; at 40.0℃; for 8.0h;
Compound 3 (1.00 g, 4.02 mmol) was combined with methyl iodide(8.04 mmol), K2CO3 (1.11 g, 8.04 mmol) and DMF (8 mL). The reaction mixture was heat to 40 C for 8 h. The reaction mixture was cooled and DMF was evaporated under reduced pressure. The residue was extracted with ethyl acetate (50 mL), filtered and evaporatedunder reduced pressure to yield the crude product, which was purifiedby column chromatography using petroleum ether and ethyl acetate(4:1) as an eluent to obtain compound 4 as a white solid: yield 89%;m.p. 93-95 C ; 1H NMR (500 MHz, CDCl3): delta 8.11 (s, 1H), 7.97 (d,J = 8.6 Hz, 2H), 6.98 (d, J = 8.6 Hz, 2H), 4.47 (q, J = 7.1 Hz, 2H), 3.89 (s, 3H), 1.45 (t, J = 7.1 Hz, 3H); 13C NMR (126 MHz, CDCl3): delta168.8, 161.63, 161.56, 147.9, 128.5, 126.2, 125.8, 114.3, 61.5, 55.4, 14.4.HRMS (ESI) m/z calcd for C13H13NNaO3S [M + Na]+: 286.0508; found:286.0521.
With potassium carbonate; In N,N-dimethyl-formamide; at 40.0℃; for 8.0h;
General procedure: The target compounds (5a-5c) were synthesized according toScheme 1. A mixture of para-hydroxythiobenzamide (1) (3.93 g, 25.67 mmol) and ethyl bromopyruvate (2) (5.00 g, 25.64 mmol) were combined in ethanol (50 mL). The reaction mixture was refluxed for 4 h, after which the reaction mixture was cooled anddistilled water (100 mL) was added to it. The precipitated solid was filtered and washed with distilled water (50 mL), dried under reduced pressure to obtain ethyl 2-(4-hydroxyphenyl)thiazole-4-carboxylate (3) as a white solid. Compound 3 (1.00 g, 4.02 mmol) was combined with methyl iodide (8.04 mmol), K2CO3 (1.11 g,8.04 mmol) and DMF (8 mL). The reaction mixture was heat to 40 Cfor 8 h. The reaction mixture was cooled and DMF was evaporated under reduced pressure. The residue was extracted with ethyl acetate (50 mL), filtered and evaporated under reduced pressure to yield the crude product that was purified by column chromatography using petroleum ether and ethyl acetate (4:1) as an eluent toobtain 2-(4-methoxyphenyl)thiazole-4-carboxylate (4) as white solid. KOH (0.83 g) was added in to the solution of compound 4 (1 g) in 15 mL anhydrous methanol and reflux for 9 h. After reaction, the solution was neutralized to pH 5 and poured into cool water (100 mL). The residue was filtered and dried to obtain the 2-(4-methoxyphenyl)thiazole-4-carboxylic acid. Sulfoxide chloride (0.45 mL) was added to the solution of 2-(4-methoxyphenyl)thiazole-4-carboxylic acid (0.4 g) in the dichloromethane (10 mL) and reflux for 10 h. When the reaction was completed, solvent was evaporated under reduced pressure. The residual mass was dissolved into dichloromethane (10 mL). Then the amine was added tothe solution and reflux for another 6 h. When the reaction was finished, the solvent was evaporated under reduced pressure. The residual was purified using column chromatograph (CH2Cl2:CH3OH 15:1) to get 2-phenylthiazole derivatives 5a-c. The forming compounds were grown at room temperature from organic solvent (methanol and dichloromethane) for single crystals of compounds 5a-5c, respectively.
General procedure: The target compounds (5a-5c) were synthesized according toScheme 1. A mixture of para-hydroxythiobenzamide (1) (3.93 g, 25.67 mmol) and ethyl bromopyruvate (2) (5.00 g, 25.64 mmol) were combined in ethanol (50 mL). The reaction mixture was refluxed for 4 h, after which the reaction mixture was cooled anddistilled water (100 mL) was added to it. The precipitated solid was filtered and washed with distilled water (50 mL), dried under reduced pressure to obtain ethyl 2-(4-hydroxyphenyl)thiazole-4-carboxylate (3) as a white solid. Compound 3 (1.00 g, 4.02 mmol) was combined with methyl iodide (8.04 mmol), K2CO3 (1.11 g,8.04 mmol) and DMF (8 mL). The reaction mixture was heat to 40 Cfor 8 h. The reaction mixture was cooled and DMF was evaporated under reduced pressure. The residue was extracted with ethyl acetate (50 mL), filtered and evaporated under reduced pressure to yield the crude product that was purified by column chromatography using petroleum ether and ethyl acetate (4:1) as an eluent toobtain <strong>[57677-79-9]2-(4-methoxyphenyl)thiazole-4-carboxylate</strong> (4) as white solid. KOH (0.83 g) was added in to the solution of compound 4 (1 g) in 15 mL anhydrous methanol and reflux for 9 h. After reaction, the solution was neutralized to pH 5 and poured into cool water (100 mL). The residue was filtered and dried to obtain the 2-(4-methoxyphenyl)thiazole-4-carboxylic acid. Sulfoxide chloride (0.45 mL) was added to the solution of 2-(4-methoxyphenyl)thiazole-4-carboxylic acid (0.4 g) in the dichloromethane (10 mL) and reflux for 10 h. When the reaction was completed, solvent was evaporated under reduced pressure. The residual mass was dissolved into dichloromethane (10 mL). Then the amine was added tothe solution and reflux for another 6 h. When the reaction was finished, the solvent was evaporated under reduced pressure. The residual was purified using column chromatograph (CH2Cl2:CH3OH 15:1) to get 2-phenylthiazole derivatives 5a-c. The forming compounds were grown at room temperature from organic solvent (methanol and dichloromethane) for single crystals of compounds 5a-5c, respectively.
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