2-​Thiophenecarboxylic acid, 3-​amino-​, methyl ester

Methyl 3-amino-2-thiophenecarboxylate

• Molecular Formula C6H7NO2S
• Average mass 157.190 Da

2-Thiophenecarboxylic acid, 3-amino-, methyl ester

Cas 22288-78-4

MW 157.19, MF C6 H7 N O2 S

1H NMR CDCL3

13C NMR CDCL3

IR

MASS

1H NMR PREDICT

13C NMR PREDICT

SYNTHESIS 1

By Pokhodylo, Nazariy T. et alFrom Synthetic Communications, 44(7), 1002-1006; 2014

2-Propenenitrile, 3-chloro-, CAS : 871-29-4

SYNTHESIS 2

Rxn NaOMe, MeOH, 0°C

Methyl thioglycolate, CAS: 2365-48-2
C3 H2 Cl N

2-Propenenitrile, 2-chloro- OR 2-chloroacrylonitrile

920-37-6

By Denoyelle, Severine et alFrom European Journal of Organic Chemistry, 2015(32), 7146-7153; 2015

 

 

SYNTHESIS 2 B

Various Annellated Thieno [4,5]imidazo[2,1-b]thiazol-6-acetic Acids

By Schnatt, HeinzFrom No pp.; 1987

Step 1

3-Amino-2-thiophenecarboxylic acid methyl ester, hydrochloride (1):

 

202.5 g (3.75 mol) sodium methoxide was dissolved in 1000 mL absolute methanol and cooled to 20 degC. Subsequently, 159.2 g (1.50 mol) thioglycolic acid methyl ester was added dropwise within 10 minutes, while the temperature was increased to 26 degC. Then 131.3 g (1.50 mol) 2-chloroacrylonitrile was added dropwise within 2.5 hours, while the temperature was kept between 24 and 26 degC by water cooling. It was stirred for 30 minutes. By addition of 130 mL of glacial acetic acid, the mixture was neutralized (pH = 6), filtered over Hyflo and the solution was largely concentrated in vacuum. The residue was partitioned between 800 mL water and 400 mL ether and the aqueous phase was extracted three times with a total of 400 mL ether. The combined organic layers were dried over magnesium sulfate and filtered. Dry HCl gas was passed into this solution for 20 minutes. The precipitate was extracted three times with 100 mL dry ether and dried (50 degC/20 mbar). Yield: 172.3 g of yellowish crystals (60 % of theory). mp 128-129 degC. TLC: solvent: Bz:Et2O = 3:1, Rf = 0.7.

 

Step 2

3-Amino-2-thiophenecarboxylic acid methyl ester (2):

 

291.4 g (1.50 mol) 3-amino-2-thiophencarboxylic acid methyl ester, hydrochloride (1) were suspended in 875 mL methylene chloride and brought to pH = 9 with saturated sodium hydrogen carbonate solution. The reaction mixture was stirred until the completion of gas evolution. The phases were separated and the aqueous phase was extracted with a total of 500 mL methylene chloride. The combined organic layers were dried over sodium sulfate, filtered and evaporated. Yield: 221.7 pale yellow crystals (95 % of theory). mp 65-66 degC. LTC: solvent: Bz:Et2O = 3:1, Rf = 0.7.

 

SYNTHESIS  3

Me thioglycolate and 2-chloroacrylonitrile, and catalyzed by sodium methoxide.

2-chloroacrylonitrile:Me thioglycolate:sodium methoxide=1:1.2:3.3, reaction temp.=25-30°C and t=4h, and using sodium methoxide as Cat, the yield of 3-amino-2-thiophenecarboxylate was 88.2%

Guangdong Huagong, 39(7), 65, 42; 2012

 

Synthesis 4

Synthesis 2010(9): 1428-1430
DOI: 10.1055/s-0029-1218697

R = METHYL,  THEN USE METHANOL AND SODIUM METHOXIDE

 

Paper

 

Bioorganic and Medicinal Chemistry, 2014, vol. 22,  7, p. 2113 - 2122

http://www.sciencedirect.com/science/article/pii/S0968089614001394

 

PAPER

Formation of stabilized organochlorogermylamines by the chelating organic substituent, 3-amino-2-methylthiophoate
Journal of Organometallic Chemistry (1991), 409, (1-2), 131-41.

 

PAPER

Structural modification of diketo acid portion in 1H-benzylindole derivatives HIV-1 integrase inhibitors
Heterocycles (2009), 78, (4), 947-959.

 

PATENT

GB 837086 1960

 

Treating 24.8 g. ClCH2CHClCN with 31.8 g. thioglycollic acid Me ester in the presence of 29.2 g. NaOMe and 280 cc. Et2O gave 72% Me ester of 3-aminothiophene-2-carboxylic acid (I), b0.1 100-2°, m. 65.5°;

 

 

SYNTHESIS

Synthesis of methyl 5-chloro-3-(methylaminosulfonyl)thiophene-2-carboxylate
Faming Zhuanli Shenqing Gongkai Shuomingshu (2008),

NaOMe, MeOH, < 20°C; 30-60 min, < 20°C

10-15°C; 4 h, 10-15°C, ..........H2O, cooled

 

1.  "PhysProp" data were obtained from Syracuse Research Corporation of Syracuse, New York (US)

Bp 101 deg cent

1. ( GB 837086 1960 MP 65.5 °C
2.  Fiesselmann, Hans; DE 1055007 1959 
3.  Ferro, Stefania; Heterocycles 2009, V78(4), Pg947-959
4.  Shi, Jie-hua; Zhejiang Gongye Daxue Xuebao 2004, Vol32(1), Pg25-28 
5.  Takahashi, Tamotsu; JP 2003146986 A 2003 
6.  Huddleston, Patrick R.; Synthetic Communications 1979, Vol9(8), Pg731-4 

 

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