Alkylation with Alkyl Halides. Scope and Limitations

Alkylation with Alkyl Halides. Scope and Limitations 

Compared to many other types of synthetic intermediates, acetylides, RC=CM (M = Li, Na, K), show a moderate reactivity towards alkyl halides in the usual organic solvents E O and THF and in liquid ammonia [2], In this respect acetylides resemble enolates C=COM. In the absence of dipolar aprodc co-solvents (DMSO or HMPT), lithium alkynylides, RC=CLi, react sluggishly in Et O or THF with most alkyl halides [2]. In liquid ammonia the alkylation of alkali acetylides with the lower (up to C-5) alkyl bromides or iodides proceeds at a satisfactory rate [5]. A certain amount of DMSO added to the reaction mixture increases the solubility of halides with a longer carbon chain. A second effect of the addition of this co-solvent is that the temperature of the reaction mixture can gradually rise as more ammonia evaporates. In this way, the reaction can proceed gradually over the range from -33 C (b.p. NH3) to room temperature. Specific alkylation on the acetylenic carbon takes place if an equivalent amount of an alkyl halide is added to dilithiated propargvl alcohol in liquid ammonia 

This reaction may be extended to other types of acetylenic alcohols such as HC CfCH lqOH and HOCCH=CHCH20H. Di-sodio compounds, which have a poor solubility in ammonia, give disappointing results. 

With metallated acetylenes the scope of successful alkylation reactions is confined to CI Br. CH3I and alkylating agents with the general structure XCH2CH2R, in which X = Br or I and R = H, alkyl, alkylO, NH2, or NR j [5,8,10,20,21]. 

Sec-alkyl halides very sluggish reaction under forcing conditions dehvdrohalogenation occurs. 

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