2.4.6- Trichlorobenzoyl chloride, Yamaguchi esterification

Esterification using 2,4,6-trichlorobenzoyl chloride (Yamaguchi reagent). 

Yamaguchi Esterification-. 2,4,6-trichlorobenzoyl chloride, (Yamaguchii Reagent). NEt3, DMAP... 

The Yamaguchi Esterification allows the mild synthesis of highly functionalized esters. After formation of a mixed anhydride between the Yamaguchi Reagent (2,4,6-trichlorobenzoyl chloride) and the carboxylic acid, the volatiles are removed and the reaction of the anhydride with an alcohol in presence of a stoichiometric amount of DMAP generates the desired ester. 

A mild method for forming ter/-butyl esters is the Yamaguchi esterification, which involves reaction of a carboxyl group with 2A6-trichlorobenzoyl chloride and triethylamine in THE The resultant mixed anhydride intermediate reacts with rm-butyl alcohol in the presence of DMAP to give the ferf-butyl ester in good yield.96... 

The Yamaguchi esterification (activation of an acid with trichlorobenzoyl chloride) is typically used to make macrolides, indicating its reliability. Unfortunately, these examples are typically done on very small scale, so a different example is shown. 

The Yamaguchi esterification utilises 2,4,6-trichlorobenzoyl chloride, also known as the Yamaguchi reagent, to form esters from carboxylic acids and alcohols. 

In a similar fashion, Dhimitruka and SantaLucia argue that the use of 2,4,6-trichlorobenzoyl chloride is not always necessary and that other inexpensive acid chlorides can be employed.15 This is attractive especially when dealing with scale-up reactions. The authors also postulate the formation of a symmetric aliphatic anhydride to explain the regioselectivity of the Yamaguchi esterification. The mechanism assumes that aliphatic carboxylates are better nucleophiles than aromatic carboxylates and... 

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