Tertiary alcohols, dehydration esterification

Normal Fischer esterification of tertiary alcohols is unsatisfactory because the acid catalyst required causes dehydration or rearrangement of the tertiary substrate. Moreover, reactions with acid chlorides or anhydrides are also of limited value for similar reasons. However, treatment of acetic anhydride with calcium carbide (or calcium hydride) followed by addition of the dry tertiary alcohol gives the desired acetate in good yield. 

Linalol is a tertiary alcohol of the formula Cj HjgO, which, with its acetic ester (and traces of other esters) forms the basis of the perfume,of bergamot and lavender oils. By dehydration linalol is converted into terpenes of which the principal are limonene and dipentene, and by esterification into its acetic ester. The examination of the essential oil at different periods of the development of the bergamot fruit has led Charabot and Laloue to the following conclusions. As the fruit matures the essential oil undergoes the following modifications —... 

Esterification of linalool requires special reaction conditions since it tends to undergo dehydration and cyclization because it is an unsaturated tertiary alcohol. These reactions can be avoided as follows esterification with ketene in the presence of an acidic esterification catalyst below 30 °C results in formation of linalyl acetate without any byproducts [71]. Esterification can be achieved in good yield, with boiling acetic anhydride, whereby the acetic acid is distilled off as it is formed a large excess of acetic anhydride must be maintained by continuous addition of anhydride to the still vessel [34]. Highly pure linalyl acetate can be obtained by transesterification of tert-butyl acetate with linalool in the presence of sodium methylate and by continuous removal of the tert-butanol formed in the process [72]. 

In general, the acid catalyzed esterification of organic acids can be accomplished easily with primary or secondary alkyl or aryl alcohols, but tertiary alcohols usually give carbonium ions which lead to dehydration. The structure of the acid is also of importance. As a rule, the more hindered the acid is alpha to the carbonyl carbon the more difficult esterification becomes (20A). 

In the forward direction, tetrahydrothiapyrone 146 served as the precursor of both 143 and 144. Metallation of 143 (an allylic sulfide) using -butyllithium, followed by a reaction of the derived carbanion with 144, gave 147 after dehydration of the intermediate tertiary alcohol. Metallation of 147 followed by alkylation of the resulting anion with bromide 145, provided 148. Hydrolysis of the THP ether followed by reduction of the allylic C-S bonds with lithium in diethylamine, gave fe-sulfide 149. This reaction would have been expected to proceed via allyic radical and/or anion intermediates and thus, loss of olefin regiochemistry might have been anticipated, but the reaction seems to have proceeded without a major problem. Esterification of the alcohol (and most likely the thiols) and reduction of the homoallyic C-S bonds with Raney-Ni, gave 150. The synthesis of CJH (1) was completed in the usual manner. 

Esters cannot be prepared from tertiary alcohols using the Fischer esterification method because these alcohols tend to dehydrate under acid conditions. Esters of phenols also cannot be prepared by Fischer esterification because the equihbrium constant for the reaction is about 10". ... 

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