8.6: Converting Alcohols into Better Leaving Groups

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One of the key features of the S_N2 reaction is that it is useful for substitution of primary (or secondary) carbon atoms. You’ve come across examples above where the leaving group is mostly a halide or sulfonate anion. Recall that conditions for substitution of an alcohol involve protonation of the alcohol first, then loss of water as a leaving group to generate a carbocation. The same holds true for primary alcohols: protonation of the alcohol occurs in the first step, but then loss of water occurs at the same time as nucleophilic attack. Since two things are involved in the rate-determining step, we say that it is S_N2.

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Along the same lines, there are other ways of making alkyl halides from alcohols. These reactions involve converting an alcohol into a better leaving group, much like when we take an alcohol and protonate it to make it into a better leaving group. The reagents we use for this are thionyl halides in pyridine (SOX₂, where X = halide) or phosphorus trihalides (PX₃, where X = halide). You’ll notice in the mechanisms for each reaction below that the rate-determining step is an S_N2 reaction.

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A similar type of reaction involves treating an alcohol with triphenylphosphine and carbon tetrahalide, according to the mechanism below:

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The reactions above form very reactive intermediates in situ that have “super leaving groups” capable of attack by halides. The resulting alkyl halides can then be isolated and used in subsequent reactions to build more complex structures. But halides are not the only type of leaving group that we can use for substitution reactions. How would you make alkyl sulfonates? One can prepare sulfonates by reacting alcohols with sulfonyl chlorides. In the mechanism of this reaction, the alcohol attacks the sulfur center like an S_N2 reaction, displacing chloride. Normally, this reaction is performed in the presence of a base (Et₃N, pyridine) that then removes the proton to generate the product.

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