Limitations of the Grignard Reaction

We recall that Grignard reagents cannot be made if acidic functional groups are also present in
the halogen compound. The Grignard reagent is destroyed by reaction with acidic hydrogen
atoms of water, alcohols, phenols, or carboxylic acid groups.
For the same reason, we must consider the structure of the carbonyl compound selected for
reaction with a Grignard reagent. If the carbonyl compound also contains a hydroxyl group, the
fastest reaction will be the destruction of the added Grignard reagent by protonation.

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Alcohol Protecting Groups
Many ways have been devised to protect acidic groups, such as an hydroxyl group, that would
interfere with Grignard reactions. One of the simplest is conversion of an alcohol to a silyl ether.

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To prevent the production of HCl, the reaction is carried out along with an amine catalyst, which
is converted to an ammonium salt.
After the alcohol has been protected, a Grignard reaction is possible. In the second step of the
reaction, when the magnesium salt is hydrolyzed, the silyl ether is hydrolyzed too.

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Acetylenic Alcohols
Alkynide ions react with carbonyl groups in much the same way as Grignard reagents do. We
recall that these ions are effective nucleophiles that will displace a halide ion from an alkyl
halide to give an alkylated alkyne. The alkynides are prepared in an acid–base reaction
with acetylene or a terminal alkyne using sodium amide in ammonia. If a carbonyl compound is
then added to the reagent, an alcohol forms after acid work-up. If the alkynide is derived from
acetylene, an acetylenic alcohol forms.
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We can also produce alkynides without using liquid ammonia. We recall that alkynes are more
acidic than alkanes. Therefore, the acid–base reaction of an alkyne with a readily available
Grignard reagent gives a Grignard reagent of the alkyne. This alkynide ion of the Grignard
reagent reacts with carbonyl compounds.