Thiols thioacids and thioesters

Thiols undergo the same types of nucleophilic reaction with carboxylic acid derivatives as do alcohols. However, reactivity tends to be increased for two reasons. First, sulfur, because of its larger size, is a better nucleophile than oxygen (see 

Section 6.1.2) second, RS is a better leaving group than RO (see Section 6.1.4), again because of size and the less localized electrons. Simple nucleophilic reactions with H2S parallel those with H2O, and those with RSH parallel those with ROH. This gives rise to carboxylic acid derivatives containing sulfur, such as thioacids and thioesters. 

Thioesters are more reactive towards nucleophilic substitution than oxygen esters, and are widely employed in natural biochemical processes because of this property. Coenzyme A is a structurally complex thiol, and functions in the transfer of acetyl groups via its thioester acetyl coenzyme A (acetyl-CoA CH3CO-SC0A). 

This familiar reaction is effective under physiological conditions because it is enzyme mediated and employs a good leaving group in the form of a thiolate anion CoAS. It is rather interesting to note that nature uses this reaction to make acetate esters from ROH nucleophiles. Nature thus uses the more reactive combination of thioester plus alcohol, rather than the acid plus alcohol combination we might initially consider to make an ester. 

We shall see some other important biological reactions of thioesters in Box 10.8. 

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