Alcohols using DCCI

N-Alkylations, especially of oxo-di- and tetra-hydro derivatives, e.g. (28)->(29), have been carried out readily using a variety of reagents such as (usual) alkyl halide/alkali, alkyl sulfate/alkali, alkyl halide, tosylate or sulfate/NaH, trialkyloxonium fluoroborate and other Meerwein-type reagents, alcohols/DCCI, diazoalkanes, alkyl carbonates, oxalates or malon-ates, oxosulfonium ylides, DMF dimethyl acetal, and triethyl orthoformate/AcjO. Also used have been alkyl halide/lithium diisopropylamide and in one case benzyl chloride on the thallium derivative. In neutral conditions 8-alkylation is observed and preparation of some 8-nucleosides has also been reported (78JOC828, 77JOC997, 72JOC3975, 72JOC3980). 

The combination of carboxyl activation by DCCI and catalysis by DMAP provides a useful method for in situ activation of carboxylic acids for reaction with alcohols. The reaction proceeds at room temperature.119... 

Since esterification is essentially a condensation reaction between a carboxylic acid and an alcohol with the elimination of water, coupling reagents such as the carbodiimides [113-115] also work well for esterification. Figure 4 shows a typical reaction using dicyclohexyl-carbodiimide (DCCI) [116]. Dicyclohexylurea is formed as a by-product. 

New evidence concerning the mechanism of DMSO-DCCI oxidation of alcohols has been obtained using (CDa)2SO the dicyclohexylurea formed in the reaction carries one D atom, showing that the previously adopted mechanism should be modified abstraction of a proton from the intermediate oxysulphonium ion is now depicted as in (121). 

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