Methyl 4,5-dichlorothiophene-2-carboxylate Chemical Properties

Boiling point:

281.3±35.0 °C(Predicted)

Density 

1.500±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

Appearance

Yellow to brown Solid

Methyl 4,5-dichlorothiophene-2-carboxylate Usage And Synthesis

Uses

Methyl 4,5-dichlorothiophene-2-carboxylate is used as a reactant in the preparation of 2-aryl indole neurokinin NK receptor antagonists in relation to optimization of amide substituent.

Synthesis

The general procedure for the synthesis of methyl 4,5-dichlorothiophene-2-carboxylate from methyl thiophene-2-carboxylate was as follows: methyl thiophene-2-carboxylate (3,142.2 g, 1 mol) was added to a mixed solution of trifluoroacetic acid (TFA, 720 mL) and concentrated sulfuric acid (H2SO4, 180 mL). After cooling the reaction mixture to 0°C, N-chlorosuccinimide (NCS, 333.8 g, 2.5 mol) was added in batches. After addition, the reaction mixture was continued to be stirred for 10 minutes. Subsequently, the reaction solution was quenched by pouring it into cold water. The precipitated solid was collected by filtration, washed with water and dried under vacuum to afford methyl 4,5-dichlorothiophene-2-carboxylate (190 g, 90% yield) as a light yellow solid with a melting point of 58-59°C (literature value 55-56°C). The product was confirmed by infrared spectroscopy (KBr) showing the carbonyl absorption peak located at 1702 cm-1. Nuclear magnetic resonance hydrogen spectrum (1H NMR, CDCl3) showed: δ 7.56 (s, 1H, H-3), 3.89 (s, 3H, -OCH3). Nuclear magnetic resonance carbon spectra (13C NMR, CDCl3) showed: δ 160.8, 132.5, 131.7, 129.6, 125.1, 52.6. Elemental analysis results (C6H4Cl2O2S) Calculated values: C, 34.14; H, 1.91; Measured values: C, 34.01; H, 2.08%. Mass spectrometry (ESI) showed a molecular ion peak m/z 212.1 [M + H]+.

References

[1] Journal of Chemical Research, 2014, vol. 38, # 10, p. 622 - 624

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