Aryl itaconic acids from aryl aldehydes and triphenylphosphoranylidene)succinic anhydride by a one pot ring opening – Wittig olefination – hydrolysis reaction.

Itaconic acid is a fatty acid that is produced by macrophages and monocytes in various organisms under stress response [1]. Also, physiologically active aryl itaconic acids such as phenyl itaconic acid are found as metabolites in plants [2] and bacteria [3]. Aryl itaconic acids are usually prepared by Stobbe-type reaction of aryl aldehydes with dialkyl succinate [4] with subsequent ester hydrolysis. The products of the Stobbe-type reaction are often Z-configurated, but mixtures of E- and Z-configurated compounds are also known. In this communication, the synthesis of 12 E-configurated aryl itaconic acids 3 is detailed, where the compounds are produced in a Wittig olefination reaction of substituted aryl carbaldehydes 2 with 2-carboxy-triphenylphosphoranylidenepropanoate, prepared in situ by reacting triphenylphosphoranylidene)succinic anhydride (1) [5] with methanol with subsequent addition of sodium methoxide, followed by a hydrolysis step with aq. NaOH. The work-up of the products obviates chromatographic separation. The compounds have been assayed for their antibacterial activity.

[1] D. Duncan, K. Auclair, Canadian Journal of Chemistry, 2022, 100(2), 104-113.

[2] A. Lao, Y. Fujimoto, T. Tatsuno, Chemical & Pharmaceutical Bulletin, 1984, 32, 723-727.

[3] M. E. Migaud, J. C. Chee-Sanford, J. M. Tiedje, J. W. Frost. Applied and Environmental Microbiology, 1996, 62(3), 974-978.

[4] K.R. Rao, G. Bagavant. Stobbe condensation. Formation of fulgenic and itaconic acids. Indian Journal of Chemistry, 1969, 7(9), 859-861.

[5] R.F. Hudson, P.A. Chopard. 245. Structure et reactions du compose d’addition: triphenylphosphine – anhydride maléique. Helvetica Chimica Acta, 1963, 46, 2178-2185.