2-AMINO-5-METHYL-THIOPHENE-3-CARBOXYLIC ACID ETHYL ESTER Chemical Properties

Melting point:

47.0 to 51.0 °C

Boiling point:

292℃

Density 

1.219±0.06 g/cm3(Predicted)

Flash point:

131℃

storage temp. 

2-8°C(protect from light)

form 

Solid

pka

0.43±0.10(Predicted)

color 

White to Light yellow

Safety Information

Hazard Codes 

Xi

Risk Statements 

20/21/22

Safety Statements 

3/7-36/37

HazardClass 

IRRITANT

HS Code 

29349990

2-AMINO-5-METHYL-THIOPHENE-3-CARBOXYLIC ACID ETHYL ESTER Usage And Synthesis

Chemical Properties

Light yellow solid

Uses

Ethyl 2-amino-5-methylthiophene-3-carboxylate is a useful intermediate for the Gewald synthesis of 2-aminothiophenes.

Synthesis

Ethyl cyanoacetate (56.6 g, 0.5 mol), sulfur powder (16.0 g, 0.5 mol) and triethylamine (50.5 g, 0.5 mol) were added sequentially to a three-necked flask containing N,N-dimethylformamide (DMF, 100 mL) and stirred until completely dissolved. Subsequently, a solution of propionaldehyde (31.9 g, 0.55 mol) in acetaldehyde (15 mL) was added slowly and dropwise. During the reaction, the internal temperature was naturally increased to 60 °C and heated at this temperature with continuous stirring. Upon completion of the reaction, the reaction mixture was slowly poured into water and extracted with ethyl acetate. The organic phases were combined, washed sequentially with water and saturated saline, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting crude product was purified by silica gel column chromatography (MERCK Kiesel gel 60, eluent 20% ethyl acetate-hexane) to afford ethyl 2-amino-5-methylthiophene-3-carboxylate (81.8 g, 89% yield). The product was characterized by 1H-NMR (400 MHz, CDCl3): δ 1.33 (t, 3H, J = 7.2 Hz), 2.26 (d, 3H, J = 1.2 Hz), 4.25 (q, 2H, J = 7.2 Hz), 5.76 (br.s, 2H), 6.61 (q, 1H, J = 1.2 Hz).

References

[1] Patent: EP1544202, 2005, A1. Location in patent: Page/Page column 53-54
[2] Journal of Sulfur Chemistry, 2014, vol. 35, # 3, p. 261 - 269
[3] Patent: US2009/131455, 2009, A1. Location in patent: Page/Page column 8
[4] Monatshefte fur Chemie, 2017, vol. 148, # 4, p. 711 - 716
[5] European Journal of Medicinal Chemistry, 2018, vol. 154, p. 324 - 340

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