Novel Route to Thiophene-2,4-diamines

Abstract

A novel and simple procedure for the construction of fully substituted thiophene-2,4-diamines using tertiary thioamides was developed. Thus, thioacetomorpholides undergo self-condensation to the corresponding 3,5-diarylthiophene-2,4-diamine derivatives in the presence of iodine and potassium carbonate in a suitable solvent and under mild conditions.

Key words

heterocycles - iodine - sulfur - cyclization - regioselectivity

• References and Notes

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• 13 General Procedure for the Synthesis of 3,5-Diarylthiophene-2,4-diamines To a stirred solution of thioacetomorpholide (2 mmol) in DMF (1 mL), I₂ (1.1 mmol, 280 mg) and anhydrous K₂CO₃ (3 mmol, 415 mg) were added. The reaction mixture was heated at 65 °C and stirred for 120 min. Then the reaction mixture was poured in H₂O (10 mL) and extracted with EtOAc (20 mL). The organic phase was separated, dried, and subjected to flash column chromatography (EtOAc–hexane, 1: 4) to afford the desired compounds as white solids.
• 14 Selected Spectral Data for Compound 4,4′-(3,5-Di-p-tolylthiophene-2,4-diyl)dimorpholine (2b) Yield: 343 mg (79%); white crystals, mp 181–183 °C. ¹H NMR (400 MHz, CDCl₃): δ = 2.31 (s, 6 H), 2.65 (t, ³ J _HH = 4.4 Hz, 4 H), 2.74 (t, ³ J _HH = 4.4 Hz, 4 H), 3.35 (t, ³ J _HH = 4.4 Hz, 4 H), 3.54 (t, ³ J _HH = 4.4 Hz, 4 H), 7.09–7.13 (m, 4 H), 7.29 (d, ³ J _HH = 8.0 Hz, 2 H), 7.39 (d, ³ J _HH = 8.0 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 21.2, 21.3, 51.6, 52.6, 66.8, 67.3, 120.4, 126.5, 128.7, 128.8, 129.8, 130.1, 132.0, 132.8, 136.3, 137.1, 143.9, 151.4. Anal. Calcd for C₂₆H₃₀N₂O₂S: C, 71.86; H, 6.96; N, 6.45; S, 7.38. Found: C, 71.83; H, 6.93; N, 6.52; S, 7.34.