Mechanochemistry for "no solvent, no base" preparation of hydantoin-based active pharmaceutical ingredients: Nitrofurantoin and dantrolene

Colacino, E.

Primo

;Porcheddu, A.

Secondo

;Halasz, I.;Charnay, C.;Delogu, F.

Funding Acquisition

;Guerra, R.;Fullenwarth, J.

2018-01-01

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Abstract

The eco-compatible, base- and waste-free, energy-efficient, low-environmental-impact, gram-scale, mechanochemical preparation of marketed drugs such as nitrofurantoin (Furantin©), dantrolene (Dantrium©) and their structurally related derivatives is herein reported. Not a drop of organic solvent was used for the entire process and high yields of pure compounds were obtained without post-reaction work-up. Hydrazones were stable in the presence of water and gaseous HCl, formed as by-products during the synthesis. Comparative mechanochemical experiments were performed using diverse milling devices and jar materials, the active pharmaceutical ingredients were analyzed by PXRD and green metrics are calculated.