Acylureas carboxylic acid chloride

Acylureas from carboxylic acid chlorides COCl CONHCON <... 

A number of protic acids have been used to catalyze acylation reactions. It is assumed that the reactions involve the generation of acylium ions. Polymeric reagents such as Nafion-H have been used for example 2-fluorobenzoyl chloride and toluene give the benzophenone derivatives with an ortho.para ratio of 4 81. ° A zeolite-catalyzed acylation (equation 6) has been reported to afford 4-dodecenoyltol-uene in 96% yield but the yields are low with short chain carboxylic acids. Early examples of the use of trifluoroacetic and perchloric acids reported good yields of products. Some more recent examples are shown in equations (7) to (9). Phosphoric and polyphosphoric acids have been used together with carboxylic acids (equation 10),anhydrides and acylureas (equation 11). °... 

The most frequently used approaches for derivatizing carboxylic acids are esterification with a variety of single-enantiomer alcohols, or formation of amides with single-enantiomer amines [234,252]. The formation of amide derivatives requires activation of the carboxylic acid by formation of the acid chloride with thionyl chloride, mixed anhydrides with chloroformates, N-acylimidazoles with 1,1 -carbonyldiimidazole or N-acylureas with dicyclohexylcarbodiimide. Esterification reactions generally re-... 

Typically, DCC (1.1 equiv) is added to a concentrated solution (0.1-1.0 M) of the carboxylic acid (1.0 equiv), amine (1.0 equiv), and catalyst (when used) in methylene chloride or acetonitrile at 0 °C. The hydrated DCC adduct, dicyclohexylurea (DCU), quickly precipitates and the reaction is generally complete within 1 h at rt. The solvents THF and DMF can be used, but are reported to reduce reaction rates and encourage the formation of the A -acylurea side product, as well as increasing racemization in chiral carboxylic acids.If the amine is initially present as the salt (i.e. amine hydrochloride), it may be neutralized by adding 1 equiv of Diisopropylethylamine prior to adding DCC however, the addition of tertiary amines (particularly Triethylamine) can facilitate A -acylurea formation and racemization. Racemization occurs via the formation of an oxazalone intermediate. The addition of coupling agents (acylation catalysts) such as 1-Hydroxybenzotriazole (HOBt), l-hydroxy-7-azabenzotriazole... 

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