Preparation of Spiropiperidines in Water

Ferenc Miklós1 and Ferenc Fülöp1,2,*

1 Institute of Pharmaceutical Chemistry and 2 Stereochemistry Research Group of the Hungarian Academy of Sciences, University of Szeged, H-6720 Szeged, Eötvös utca 6, Hungary

* Corresponding author: E-mail:

An environmentally benign spirocyclization is described for the synthesis of 4-spiropiperidines from 2-aminocarbohydrazides in water at room temperature without any catalyst. The condensation of carbocyclic 2-aminocarbohydrazides with N-benzylpiperidinone (2) led to 3’-aminospiropiperidine-quinazolinones (3a-3d). Anthranilic hydrazide 4 gave 2- amino-N’-(1-benzylpiperidin-4-ylidene)benzohydrazide (7), while glycine hydrazide (8) reacted with 2 moles of 2 to afford 1-benzylpiperidin-4-ylidenamino-1,4,8-triazaspiro[4.5]decane (9). All products precipitated from the reaction mixture and were obtained in excellent yields. No further work-up or purification was necessary.

Keywords: Spirocyclization, spiropiperidines, spiroquinazolines, green synthesis, aqueous media, methylene-bridged quinazolines