Aldehydes reaction with chloroacetonitrile

The Darzens reaction between aldehydes and ketones with activated halomethyl compounds is an effective route to oxiranes under phase-transfer catalytic conditions and the catalyst has a profound stereochemical control of the substituents (see Chapter 12). The reaction has been conducted in high yield under liquidtliquid and solidrliquid two-phase conditions with a range of halomethyl compounds [e.g. 25-30], Ketones tend to be much slower in their reaction and benzylic ketones undergo alkylation with chloroacetonitrile in preference to the Darzens reaction [25]. 

Darzens reactions of aromatic aldehydes and a-chloroacetonitriles, oc-chloroalkyl sulfones, or phenacyl halides with ephedrine or quinine derivatives as catalysts afforded epoxides in low optical yields... 

A further method used to prepare dehydropiperazinediones is the condensation of a-keto esters with chloroacetamide or chloroacetonitrile leading to (38), followed by treatment with ammonia 367, 372, 375). For a similar cyclization reaction with concomitant dehydration see ref. (374). Subsequent condensation with aldehydes affords unsymmetrical tetradehydropiperazinediones, exemplified by the synthesis of albonoursin (36) (367, 369). Arylidenepiperazinediones from condensation reactions always have the Z-configuration, in contrast to the alkylidenepiperazine-diones, which are normally obtained as Z/E mixtures (57,140, 381). 

A degree of stereoselective control of the course of a reaction, which is absent or different from that prevalent when the reaction is conducted in the absence of quaternary ammonium salts, may be achieved under standard phase-transfer catalysed reaction conditions. The reactions, which are influenced most by the phase-transfer catalyst, are those involving anionic intermediates whose preferred conformations or configurations can be controlled by the cationic species across the interface of the two-phase system. For example, in the base-catalysed Darzens condensation of aromatic aldehydes with a-chloroacetonitriles to produce oxiranes (Section 6.3), the intermediate anion may adopt either of the two conformations, (la) or (lb) which are stabilized by interaction across the interface by the cations (Scheme 12.1) [1-4]. 

Synthesis of Dithiocarboxylic Acids and their Derivatives.—The preparation of thioterephthalic acid from l,4-di(chloromethyl)benzene, sulphur, and sodium methoxide (see Vol. 5, p. 179) has beeil reported by another group. In a similar reaction, the addition of chloroacetonitrile to sulphur and triethylamine in DMF, followed by alkylation, gave methyl and ethyl cyanodithioformates. These were not isolated, but they condensed when water was added, giving EfZ mixtures of l,2-di(alkylmercapto)-l,2-dicyanoethylenes. Ethylene dithioacetals from aromatic aldehydes are decomposed by sodium hydride in DMF containing HMPA, with elimination of ethylene and the liberation of an aryIdithiocarboxylate anion this may be alkylated to give the dithioester (Scheme 8). ... 

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