Alkylation acetylide ions

Acetylide ion alkylation is limited to primary alkyl bromides and iodides, RCHgX, for reasons that will be discussed in detail in Chapter 11. In addition to their reactivity as nucleophiles, acetylide ions are sufficiently strong bases that they cause dehydrohalogenation instead of substitution when they react with secondary and tertiary alkyl halides. For example, reaction of bromocyclohexane with propyne anion yields the elimination product cyclohexene rather than the substitution product cyclohexylpropyne. 

Acetylide ion alkylation is an Sn2 reaction, and it s therefore understandable that only primary alkyl halides and tosylates react well. Since acetylide anion is a strong base as well as a good nucleophile, E2 elimination competes with Sn2 alkylation when a secondary or tertiary substrate is used. For example, reaction of sodio ]-hexyne with 2-bromopropane gives primarily the elimination product rather than the substitution product ... 

Next an alkyl halide (the alkylating agent) is added to the solution of sodium acetylide Acetylide ion acts as a nucleophile displacing halide from carbon and forming a new carbon-carbon bond Substitution occurs by an 8 2 mechanism... 

The properties of organometallic compounds are much different from those of the other classes we have studied to this point Most important many organometallic com pounds are powerful sources of nucleophilic carbon something that makes them espe cially valuable to the synthetic organic chemist For example the preparation of alkynes by the reaction of sodium acetylide with alkyl halides (Section 9 6) depends on the presence of a negatively charged nucleophilic carbon m acetylide ion... 

Both CH3CH2CH2C=CH and CH3CH2C=CCH3 can be prepared by alkylation of acety lene The alkyne (CH3)2CHC=CH cannot be prepared by alkylation of acetylene because the required alkyl halide (CH3)2CHBr is secondary and will react with the strongly basic acetylide ion by elimination... 

It looks as though all that is needed is to prepare the acetylenic anion, then alkylate it with methyl iodide (Section 9.6). There is a complication, however. The carbonyl group in the starting alkyne will neither tolerate the strongly basic conditions required for anion fonnation nor survive in a solution containing carbanions. Acetylide ions add to carbonyl... 

We won t study the details of this substitution reaction until Chapter 11 but for now can picture it as happening by the pathway shown in Figure 8.6. The nucleophilic acetylide ion uses an electron pair to form a bond to the positively polarized, electrophilic carbon atom of bromomethane. As the new C-C bond forms, Br- departs, taking with it the electron pair from the former C-Br bond and yielding propyne as product. We call such a reaction an alkylation because a new alkyl group has become attached to the starting alkyne. 

In these alkylation reactions primary alkyl halides (the bromide for preference) should be used as the alkylating agents, since secondary and tertiary halides undergo extensive olefin-forming elimination reactions in the presence of the strongly basic acetylide ion. A typical synthesis is that of hex-l-yne (Expt 5.26). 

The reaction of an acetylide ion with a primary alkyl halide allows the synthesis of di-substituted alkynes [Following fig.(a)]. 

Show how to synthesize alkynes by eliminations from alkyl halides and by the additions and substitutions of acetylide ions. 

Acetylide ions are strong nucleophiles. In fact, one of the best methods for synthesizing substituted alkynes is a nucleophilic attack by an acetylide ion on an unhindered alkyl halide. We consider this displacement reaction in detail in Section 9-7A. 

Two different approaches are commonly used for the synthesis of alkynes. In the first, an appropriate electrophile undergoes nucleophilic attack by an acetylide ion. The electrophile may be an unhindered primary alkyl halide (undergoes Sn2), or it may be a carbonyl compound (undergoes addition to give an alcohol). Either reaction joins two fragments and gives a product with a lengthened carbon skeleton. This approach is used in many laboratory syntheses of alkynes. 

If this Sn2 reaction is to produce a good yield, the alkyl halide must be an excellent SN2 substrate It must be methyl or primary, with no bulky substituents or branches close to the reaction center. In the following examples, acetylide ions displace primary halides to form elongated alkynes. 

Alkylation of acetylide ions is an excellent way of lengthening a carbon chain.The triple bond can later be reduced (to an alkane or an alkene) if needed. 

In all of these problems, an acetylide ion (or an anion of a terminal alkyne) is alkylated by haloalkane. 

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