[31667-72-8]  · (C7H12N2)n  · Polyhexamethylenecarbodiimide  · (MW )n(124.21)

(insoluble carbodiimide condensation reagent)

Solubility: insol CH2Cl2.

Preparative Method: by catalytic decarboxylation of 1,6-diisocyanatohexane, followed by several purification steps.1

Peptide Bond Formation.1

In what may be termed a reverse Merrifield approach, an N-protected amino acid is reacted with a sizable molar excess of the polymeric carbodiimide, suspended in CH2Cl2, and an equimolar amount of a C-protected amino acid (side chain reactive groups of the amino acid derivatives also appropriately protected). After removal of the catalyst by filtration, and washing with aqueous acid and base, evaporation of solvent leaves the substantially pure coupled material in good yields (82-93%).

The coupling and workup procedures are similar to those used in the classical 1,3-Dicyclohexylcarbodiimide coupling. Both this and the water-soluble carbodiimide 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Hydrochloride, which requires no filtration step, are commercially available, and perform these same reactions with equal facility. They are, moreover, required in only stoichiometric proportions, and are accordingly very widely used, in distinct contrast to this polymeric reagent.

Other insoluble polymeric carbodiimides2 have also been reported. Another,3 which is soluble in typical reaction solvents (CH2Cl2, DMF, DMSO), but subsequently precipitated by addition of ether, is also known. None of these appear to have found any great popularity either.

1. Wolman, Y.; Kivity, S.; Frankel, M. CC 1967, 629.
2. (a) Akelah, A. S 1981, 413. (b) Weinshenker, N. M.; Shen, C. M.; Wong, J. Y. OSC 1988, 6, 951. (c) Ito, H.; Takamatsu, N.; Ichikizaki, I. CL 1975, 577.
3. Mutter, M. TL 1978, 2843.

Peter Ham

SmithKline Beecham Pharmaceuticals, Harlow, UK

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