IIDQ-polystyrene

IIDQ-polystyrene (IIDQ-PS) ^[1] is a polymer-supported version of the IIDQ coupling reagent ^[2]. IIDQ has many advantages over conventional carbodiimide- or uronium-based reagents: no preactivation step is required, and acid, amine and coupling reagent can be added in any order; in contrast to uronium-based reagents like HBTU, it cannot form guanidinium by-products; and it is totally stable to base. The treatment of a carboxylic acid with IIDQ-PS in DCM or MeCN rapidly generates in situ the corresponding isobutoxycarbonyl mixed anhydride ^[3]. Attack by nucleophiles preferentially takes place at the less hindered and more electrophilic carbonyl of the carboxylic acid moiety, releasing only volatile carbon dioxide and isobutanol as by-products. If reaction is carried out in the presence of an amine, amide bond formation occurs concurrently with generation of the anhydride. Alternatively, addition of NaBH₄ or polymer-supported borohydride to the anhydride will lead directly to the corresponding alcohol. IIDQ-PS appears to be particularly effective for mediating the acylation for anilines, and has also been found to couple peptide fragments without epimerization. In a comparative study, IIDQ-PS was found to give higher yields and greater purities than HATU, EDC-PS or DCC-PS ^[4]. Occasionally, with some secondary amines the formation of isobutyl carbamate by-products has been observed, resulting from attack by the amine at the carbonyl group.

Literature references

^[1] E. Valeur, et al. (2005) Chem. Commun., 1164.
^[2] Y. Kiso, et al. (1973) Chem. Pharm. Bull., 21, 2507.
^[3] J. R. Vaughan (1951) J. Am. Chem. Soc., 73, 3547.
^[4] E. Valeur & M. Bradley, unpublished results.

Replaces: 01-64-0469

Color (visual): yellow to beige to amber
Appearance of substance (visual): beads
Loading (determined by HPLC after reaction of 3-phenylpropionic acid with cyclohexlamine): 1.3 - 1.9 mmol/g
Swelling Volume (in DMF): lot specific result
The polymer matrix is copoly (styrene-1 % DVB) 200 - 400 mesh.

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