Substituted Selenophenes Starting from Ketene Dithioacetals and Sodium Selenide

Abstract

Various substituted selenophenes 2 can easily be synthesised in two steps by using sodium selenide, ketene dithioacetals 1 and activated methylene compounds.

Key words

selenium - heterocycles - cyclizations - acetals - nucleophilic additions

References

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4

Sommen, G.; Comel, A.; Kirsch, G. Synthesis 2003, in press.

15

Preparation of sodium selenide Na₂Se: Selenium (0.8 g) was added to a solution of NaOH (2.25 g) and sodium formaldehyde sulfoxylate (2.85 g) in H₂O (10 mL). After stirring at 60 °C for 1 h, a white precipitate appeared. After cooling at 0 °C, the selenide was filtered under an inert atmosphere and rapidly used in the next step.
Typical Procedure for the Preparation of Selenophenes 2: A 100mL three-necked round-bottom flask equipped with magnetic stirrer, condenser and septum was charged with freshly prepared sodium selenide (10.0 mmol, 1 equiv) in DMF (30 mL). Ketene dithioacetal (10.0 mmol, 1 equiv), was added and the mixture was stirred for 2 h at 50 °C. The halide (10.0 mmol, 1 equiv) was then added dropwise and the mixture was stirred for 1 h before adding the dried K₂CO₃ (1.38 g, 1 equiv). The reaction was quenched with 100 mL of H₂O after having stirred 3 h at 50 °C. The crude product precipitated was filtered and purified by crystallisation from isopropanol.
Representative Spectroscopic Data: 4-Acetyl-3-methyl-5-methylsulfanylselenophene-2-carboxylic acid ethyl ester 2a : Mp: 88-90 °C. ¹H NMR (250 MHz, CDCl₃): 1.37 (t, 3 H, J = 7.2 Hz), 2.52 (s, 3 H), 2.57 (s, 3 H), 2.72 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl₃): δ = 14.3 (CH₃), 17.3 (CH₃), 21.0 (CH₃), 31.3 (CH₃), 61.1 (CH₂), 140.4, 141.4, 147.4, 147.5, 162.9 (CO₂), 196.9 (CO). MS: m/z = 43(100), 83(28), 263(35), 291(63), 306(50). IR (KBr): 1701, 1635, 1526, 1375, 1209, 1251 cm^-1. Anal. Calcd for C₁₁H₁₄O₃SSe: C, 43.28; H, 4.62. Found: C, 43.22; H, 4.50.
3,5-Diacetyl-4-methyl-2-methylsulfanylselenophene 2b: Mp: 76-78 °C. ¹H NMR (250 MHz, CDCl₃): δ = 2.53 (s, 3 H), 2.54 (s, 3 H), 2.55 (s, 3 H), 2.61 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl₃): δ = 17.8 (CH₃), 20.8 (CH₃), 30.5 (CH₃), 31.2 (CH₃), 141.7, 141.9, 144.2, 160.7, 191.4 (CO), 197.3 (CO). MS: m/z = 43(100), 83(13), 261(48), 276(30). IR (KBr): 1634, 1613, 1504, 1418, 1346, 1368, 1278, 1203 cm^-1. Anal. Calcd for C₁₀H₁₂O₂SSe: C, 43.64; H, 4.39. Found: C, 43.57; H, 4.31.