Benzotriazoles urea synthesis

Paio A, Crespo RF, Seneci P, Ciraco M, Solid-supported benzotriazoles. 2. Synthetic auxiliaries and traceless linkers for the combinatorial synthesis of unsymmetrical ureas, J. Comb. Chem., 3 354-359, 2001. 

For the parallel synthesis of ureas based on amino acids, a solid-phase synthesis as well as a solution-phase synthesis were used (Scheme 5) [11]. Solution-phase synthesis gave the desired compounds 21 in yields ranging from 80-100% and purities in the range 71-97%. The work-up involved extraction of the benzotriazole formed in the coupling steps. An aqueous borax buffer (pH 9.2) was used and the separation of the CH2CI2 layer from the aqueous phase was performed in cartridges equipped with a PTFE frit. 

Phosphoranylideneaminoquinones, e.g. (20), have been prepared in good to excellent yields by the reaction of phosphines with [2,l]benzisoxazole-4,7-quinones, e.g. (19)." A safer alternative to the vinyl azide-based synthesis of (N-vinylimino)phosphoranes (21) has been reported (Scheme 1)." N-(AlkyIthiomethyl)iminophosphoranes (23) have been synthesised from the benzotriazole-substituted iminophosphorane (22) and used without isolation to provide routes to N-alkylthiomethyl-imines, -amides, and -ureas. Tetraazolyl-substituted ylides (25) and (26) are the products of the reaction of vinylphosphonium salts (24) with excess sodium azide." The novel 1,2-1 -azaphosphete (28), which is potentially antiaromatic, has been prepared by the reaction of the azide... 

An early example of benzotriazole utility was the synthesis of a wide range of unsymmetrical tetra-substituted ureas (4) by reaction of 1,1 -carbonylbis-benzotriazole (2), generated in 90% yield from two equivalents of BtH and phosgene, with secondary amines (Scheme 2). The formation of ureas (4) was achieved in two steps via (3), and high yields were reported for both series of compounds (1997JOC4155). 

A further application of the benzotriazole linker is the synthesis of fi-diketones 382. Polymer-supported benzotriazoles 371 were transformed into the corresponding azolides which were cleaved with various ketone hhio eno-lates to build diketones 382 [261]. Other cleavage reactions with nucleophiles should be possible as benzotriazole auxiliaries are often used as advantageous N, C-, S- and 0-acylating reagents [262]. A well-known application is the solid phase synthesis of unsymmetric ureas (R = NR2) with secondary amines as cleaving nucleophiles [258]. 

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