2-thienylmethyl chloride

Emerson and Patrick (1949) obtained it by treatment of thenyl chloride (2-thienylmethyl chloride) with sodium acetate and triethyl amine. 

The industrial synthesis of thiophene is based on butane and its reaction with sulfur or carbon disulfide. In comparison with benzene, thiophene can be more easily substituted electrophilically in the 2- or 5- position this reaction is used to produce a wide range of pharmaceutical products. An example of this is the antihistamine thenalidine, which is obtained from thiophene by chloromethylation to 2-thienylmethyl chloride followed by reaction with 4-anilino-l-methylpiperidine. 

A number of 2-substituted imidazoles were found to be 4(5)-alkylated by soft electrophiles. Thus, 2-phenylimidazole (112) reacts with 3-thienylmethyl bromide to give mainly 4- and 4,5-di-substituted products A-alkylation occurs only to a minor extent (Equation 2). Similarly, 2-methoxybenzyl chloride gives rise mainly to C-substituted products. Benzyl bromide, a harder electrophile, gives largely A-benzyl derivatives of (112). 

Reaction of 2-benzo[6]thienyllithium (and its 7-methyl derivative 90) with aldehydes 486,5fl4, 620 or ketones 467 483 affords a secondary or tertiary alcohol, respectively. Treatment of 2-benzo[6]thienyl-lithium with acetyl chloride gives mainly l,l-di(2-benzo[6]thienyl)-ethylene.132 Side-chain alcohols in positions other than the 2-position are most easily prepared by reaction of the appropriate benzo[6]-thienylmagnesium halide with aldehydes 460,471 or ketones,186,3o9, 349, 4 7,466,479,498 or foy reaction of a benzo[fe]thiophene aldehyde, ketone, or ester with an alkylmagnesium halide.358,427 465 The preparation of alcohols from 2- and 3-benzo[6]thienylmethyl-magnesium chloride485,528 is discussed in Section VI, D, 4. 

Synthesis of 3-methoxy-2-thienylmethyl(triphenyl)phosphonium chloride (R. A. Aitken and A. N. Garnett, unpublished data)... 

Ethanthiol 2-(2-Thienylmethyl-amino)- lV/ld, 467 Ammonium Dimethyl-(2-pyrrolyl-methylen)- -chlorid E14a/3, 254 (l-SiR3 —pyrrol + DMF/ Cl-OC-CO-Cl)... 

The scope of the reactions of 5-nitro-3-thienylethyl chloride and acetate with the lithium salt of 2-nitropropane to give (83) (cf. this series, Vol. 2, p. 80) has been investigated. The cyano-group was not found to be sufficiently active, since 4-cyano-2-thienyl-methyl and -ethyl chlorides only gave O-alkylated products by an mechanism. The iSn(AEAE) reaction also occurred between benzenethiolate and 4-nitro-2-thienylmethyl acetate, and a moderate yield of 4-nitro-2-thienylmethyl phenyl sulphide was obtained. 

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