CAS No. :	3973-08-8
Formula :	C₄H₃NO₂S
M.W :	129.14
SMILES Code :	O=C(C1=CSC=N1)O
MDL No. :	MFCD00623589
InChI Key :	HMVYYTRDXNKRBQ-UHFFFAOYSA-N
Pubchem ID :	304271

Safety of 4-Thiazolecarboxylic acid

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H317-H320
Precautionary Statements:	P261-P264-P272-P280-P302+P352-P305+P351+P338-P321-P333+P313-P337+P313-P363-P501

Application In Synthesis of 4-Thiazolecarboxylic acid

* 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.

Downstream synthetic route of [ 3973-08-8 ]

[ 3973-08-8 ] Synthesis Path-Downstream 1~54

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[ 3973-08-8 ]
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Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; for 5h;	General procedure: 2.5mmol thiazole-4-carboxyli acid and 2.0mmol alcohol were dissolved in 25mL dichloromethane (DCM) in a dry flask with continuous stirring, followed by the addition of 2.5mmol 3-(3-dimethylaminopropyl) -1-ethylcarbodiimide hydrochloride. When the temperature of the reaction system cooled to 0C, 0.2mmol 4-dimethylaminopyridine was added dropwise and reacted for 1hat 0C. Then the temperature was elevated to room temperature for another 4h reaction. The reaction was stopped by adding 25mL saturated NaHCO3 solution and extracted twice with 20mL dichloromethane (2×20mL). The extracted organic layers were first dried by anhydrous Na2SO4, and then filtered and concentrated under vacuum distillation, obtaining the crude products. Finally, the crude products were further purified using column chromatography (ethy lacetate:petroleum ether, 1:5). 5.1.1.1 36 Methyl thiazole-4-carboxylate (B-1) Light yellow solid; 53.4% yield; 97.06% purity. 1H NMR (300MHz, CDCl3) delta 8.85 (d, J=2.1Hz, 1H), 8.25 (d, J=2.1Hz, 1H), 3.96 (s, 3H). 13C NMR (75MHz, CDCl3) delta 161.8, 153.5, 147.9, 127.4, 52.5. HRMS-ESI (m/z): calcd for C5H5NO2S [M+H]+: 144.0114, found 144.0010. Mp: 73.7-73.9C.

References: [1]Organic Letters,2008,vol. 10,p. 2909 - 2912.
[2]Chemistry - A European Journal,2011,vol. 17,p. 14450 - 14463.
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Chem.Abstr.,1953,p. 12358.
[4]European Journal of Medicinal Chemistry,2018,vol. 145,p. 64 - 73.

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[ 3745-79-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With thionyl chloride; for 2h;Heating / reflux;	Preparation 96A; Thiazole-4-carbonyl chlorideA mixture of thiazole-4-carboxylic acid (30.0 g, 232 mmol) and thionyl chloride (200 ml.) was heated at reflux for 2h. The resulting solution was evaporated and the residue dried giving a yellow solid. Yield 34.0 g, 99%. 1H NMR (CDCI3) delta 8.91 (d, 1H, J = 2 Hz)1 8.49 (d, 1H, J = 2 Hz).
80.5%	With thionyl chloride; for 2h;Reflux;	Weigh 0.25g (1.94mmol)<strong>[3973-08-8]Thiazole-4-carboxylic acid</strong> in a 50 mL round bottom bottle,2.81 mL of thionyl chloride was added and stirred at reflux for 2 h.The reaction was monitored by TLC (methanol: dichloro = 1:2).The reaction solution was concentrated under reduced pressure to give a pale yellow solid.0.23g (1.56mmol),The yield was 80.50%.
	With oxalyl dichloride; In dichloromethane; at 0℃; for 1h;	Step A:; To an ice-cold solution of 1,3-thiozol-4-carboxylic acid (276 mg, 2.14 mmol) in dichloromethane (20 mL) was added oxalyl chloride (0.21 mL, 2.14 mmol) dropwise. The ice bath was removed and stirring was continued for 1 h. 2-Amino-3-hydroxybenzoic acid hydrobromide (500 mg, 2.14 mmol) was added followed by triethylamine (0.90 mL, 6.42 mmol). The resulting reaction mixture was stirred at room temperature overnight. The reaction was quenched with aqueous 1 N HCl (25 mL), until the solution reached pH 1. The reaction mixture was extracted with dichloromethane. The combined organic layers were dried over Na2SO4, filtered and concentrated to a brown solid. The crude was dissolved in toluene (10 mL) and the solution was treated with p-toluenesulfonic acid monohydrate (458 mg, 2.40 mmol). The resulting reaction mixture was then heated to reflux under nitrogen for 2 h. The reaction was cooled down to room temperature, poured into water and extracted with ethyl acetate (400 mL). The organic layer was separated then washed with water, brine, dried over Na2SO4, filtered and concentrated to an off-white solid. The crude product was purified by recrystallization from ethyl acetate to afford the desired product (145 mg, 27%) as a light yellow solid: 1H NMR (500 MHz, DMSO-d6) delta 13.25 (br s, 1H), 9.37 (d, J=1.9 Hz, 1H), 8.82 (d, J=1.9 Hz, 1H), 8.06 (dd, J=7.2, 0.9 Hz, 1H), 7.94 (dd, J=7.8, 0.9 Hz, 1H), 2.87 (t, J=7.9 Hz, 1H); MS (ESI+) m/z 247 (M+H).

	With thionyl chloride;	EXAMPLE 23 Thiazole-4-carbonyl chloride <strong>[3973-08-8]Thiazole-4-carboxylic acid</strong>, 0.97 g, is refluxed 1 1/2 hours with 10 ml thionyl chloride, evaporated, flushed with benzene and recrystallized from 50 ml hexane to yield thiazole-4-carbonyl chloride, m.p. 85. IR (mu, CHCl3): 5.64. NMR (delta, CDCl3): 9.01d, 8.59d, J=2.
	With thionyl chloride; for 2h;Reflux;	General procedure: I (1-1.5 eq.) was refluxed in SOCl2 (3-5 ml) for 2 h. An excess of SOCl2 was evaporated in vacuo and pyridine (3 ml) was added to the resulting residue. The mixture was then stirred for 10 min., IV (1 mmol) was added and the resulting mixture was stirred overnight at rt
	With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	A suspension of Ala (10.0 g, 77.4 mmol, Combi Blocks) in DCM (100 mL) is treated with oxalyl chloride (66.0 mL, 619.5 mmol). Then, DMF (599.6 iL, 7.7 mmol) is added dropwise. The reaction mixture is stirred overnight at RT, and then concentrated under reduced pressure, azeotroped with toluene (150 mL) and dried under high vacuum for 1 h to afford Alb which is used as is in subsequent reactions.
	With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 20℃;	Example Al: Preparation of compound Al bHO cIAla AlbAla (10.0 g, 77.4 mmol, Combi Blocks) in DCM (100 mL) is treated with oxalyl chloride (66.0 mL, 619.5 mmol). DMF (599.6 iL, 7.7 mmol) is then added dropwise causing gas evolution. The reaction mixture is stirred overnight at RT, and then concentrated under reduced pressure, azeotroped with toluene (150 mL) and dried under high vacuum for 1 h to afford Alb which is used as is in subsequent reactions.
	With thionyl chloride; for 2h;Heating / reflux;	Preparation of nitrile intermediates (Method A); The desired carboxylic acid (1 g) was refluxed in 10 ml of SOCI2 for 2h. SOCI2 was removed under reduced pressure. Dry toluene was added. The solution was cooled to O0C with ice bath. Ammonia was bubbled in toluene for 30 min. Solid was filtered and the filtrate was concentrated to obtain the crude amide which was used to next step without further purification.To a stirred mixture of amide (1.0 eq) and Et3N (4.5eq) was added dropwise (CF3CO)2theta (TFFA, 2 eq) at - 780C under N2. The mixture was stirred overnight at room temperature. Ice water was added to destroy TFAA. The mixture was extracted with CH2Cl2. The organic phases were combined, dried over Na2Stheta4 and concentrated to afford the product.
	With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20 - 35℃;	To l,3-thiazole-4-carboxylic acid (0.423 g, 3.28 mmol) in CH2Cl2 (10 mL) was added oxalyl chloride (0.34 mL, 3.93 mL) and DMF (5 drops). The reaction was warmed momentarily Io about 30-35 0C and then stirred at rt for 2 h. The reaction was concentrated to afford the product

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[18]ChemMedChem,2019,vol. 14,p. 1662 - 1668.

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[ 635-46-1 ]
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References: [1]Helvetica Chimica Acta,1948,vol. 31,p. 924,925.

4
[ 100367-77-9 ]
[ 3973-08-8 ]

References: [1]Helvetica Chimica Acta,1942,vol. 25,p. 1075.

5
[ 89791-92-4 ]
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References: [1]Journal of the Chemical Society,1957,p. 689,696.

6
[ 89791-92-4 ]
[ 3973-08-8 ]
[ 89379-29-3 ]

References: [1]Journal of the Chemical Society,1957,p. 689,696.

7
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References: [1]Journal of the Chemical Society,1957,p. 689,696.

8
[ 22358-80-1 ]
[ 108-24-7 ]
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References: [1]Helvetica Chimica Acta,1937,vol. 20,p. 204.

9
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References: [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1953,vol. 73,p. 126.
Chem.Abstr.,1953,p. 12358.

10
[ 7113-13-5 ]
[ 3973-08-8 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1966,vol. 16,p. 1357 - 1360.

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[ 763025-08-7 ]
[ 58603-92-2 ]

References: [1]Journal of Medicinal Chemistry,1976,vol. 19,p. 695 - 709.

12
[ 3973-08-8 ]
[ 124-40-3 ]
[ 64649-22-5 ]

References: [1]Tetrahedron,1977,vol. 33,p. 1337 - 1343.

13
[ 3973-08-8 ]
[ 62-53-3 ]
[ 88218-99-9 ]

References: [1]Journal of general chemistry of the USSR,1961,vol. 31,p. 2444 - 2448.
Zhurnal Obshchei Khimii,1961,vol. 31,p. 2618 - 2623.

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[ 3973-08-8 ]
[ 62-53-3 ]
[ 93336-05-1 ]

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Zhurnal Obshchei Khimii,1961,vol. 31,p. 2618 - 2623.

15
[ 3973-08-8 ]
[ 108-95-2 ]
[ 30216-60-5 ]

References: [1]Canadian Journal of Chemistry,1970,vol. 48,p. 3554 - 3562.

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[ 30256-48-5 ]

References: [1]Canadian Journal of Chemistry,1970,vol. 48,p. 3554 - 3562.

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Yield	Reaction Conditions	Operation in experiment
70.2%	With potassium permanganate; In water; at 55℃; for 22h;	4-methylthiazole (19.8 g, 0.2 mol),200 mL of water and potassium permanganate (173.8 g, 1.1 mol) were placed in a 500 mL three-neck reaction flask and heated to 55° C. for 22 h with stirring and heating.The reaction solution was then cooled and then filtered. The filter cake (manganese dioxide) was washed with hot water at 50°C, and the filtrate was adjusted to pH 3 with dilute hydrochloric acid.A solid precipitated and was filtered. The filter cake was washed with a small amount of water. The product was dried to give 18.1 g, yield 70.2percent, melting point 196-198°C.

References: [1]Angewandte Chemie,1992,vol. 104,p. 748 - 749.
[2]Patent: CN104557902,2018,B .Location in patent: Paragraph 0063; 0076; 0081; 0088; 0089; 0102.

18
[ 186581-53-3 ]
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[ 59418-09-6 ]

References: [1]Tetrahedron Letters,1995,vol. 36,p. 9293 - 9296.

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[ 89379-29-3 ]
[ 3973-08-8 ]

References: [1]Helvetica Chimica Acta,1948,vol. 31,p. 1342,1348.

24
[ 3973-08-8 ]
[ 5259-87-0 ]
Sodium; 2-(2-phenylacetylamino-acetyl)-thiazole-4-carboxylate [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2001,vol. 9,p. 2035 - 2044.

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[ 115-08-2 ]
[ 1113-59-3 ]
[ 3973-08-8 ]

References: [1]Bioorganic and Medicinal Chemistry,2001,vol. 9,p. 2035 - 2044.

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[ 3973-08-8 ]
[ 439905-31-4 ]
[ 439904-99-1 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 561 - 565.

27
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2-amino-N-[1-hydroxymethyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-2-oxo-ethyl]-thioacetamide [ No CAS ]
Thiazole-4-carboxylic acid [(R)-1-hydroxymethyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-2-oxo-ethylthiocarbamoyl]-methyl}-amide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 561 - 565.

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[ 3973-08-8 ]
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[ 439905-08-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 561 - 565.

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[ 473421-31-7 ]
(2R)-N-(4-methoxybenzyl)-3-cyclohexylmethylthio-2-(thiazol-4-ylcarbonyl-amino)propanamide [ No CAS ]

References: [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 915 - 918.

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S-cyclohexylmethyl-L-cysteine 4-methoxybenzylamide hydrochloride [ No CAS ]
(2R)-N-(4-methoxybenzyl)-3-cyclohexylmethylthio-2-(thiazol-4-ylcarbonyl-amino)propanamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 1901 - 1913.

31
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References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2929 - 2932.

32
[ 696603-01-7 ]
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Thiazole-4-carboxylic acid [1-((E)-3-phenyl-allyl)-piperidin-4-yl]-amide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 3412 - 3416.

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[ 3973-08-8 ]
[ 479255-66-8 ]
cyclohexyl 2-deoxy-2-(thiazole-4-carbonylamino)-1-thio-α-D-glucopyranoside [ No CAS ]

References: [1]Journal of Carbohydrate Chemistry,2005,vol. 24,p. 103 - 130.

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[3-(1-benzo[1,3]dioxol-5-ylmethyl-piperidin-4-ylamino)-5-chloro-indazol-1-yl]-thiazol-4-yl-methanone [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 5293 - 5297.

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