Solid-state rearrangement reactions of acylated aminopyrazoles

• Main Author: Clelland, Iain C.
• Published: University of Edinburgh 1999
• Subjects: 547.59
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.643257

The thermally induced solid-state rearrangement reactions of acylated aminopyrazoles were investigated. The precursors were generally formed by mono-acylating 3-aminopyrazole with an acid chloride in solution, and obtaining an isolated individual isomer by dry fresh chromatography. The rearrangements proceed under remarkably mild conditions (at room temperature or below), at temperatures of up to 100°C below the melting point. The reaction can still occur in the melt but not to any extent in solution. The reaction proceeds in all cases from the 1 (r) 3-isomer and from the 2 (r) 3-isomer and for many acyl substituents the rearrangements occur in tandem with the 2-isomer rearranging to the 1- and 3-isomers concurrently. However the migration of the acyl group from the 1 (r) 2-isomer has not been seen as might have be expected. The solid-state rearrangements work for a wide range of acyl substituents, even occurring when the structure of the pyrazole ring is altered or when different ring systems are used (<i>e.g.</i> indazoles). The half-lives of reaction for individual acyl substituents and isomers vary from hours to years. The tendency is for the rearrangement of the 2 (r) 3-isomer to be faster than its counterpart 1 (r) 3, though there are exceptions to this. The overall conclusion is that, having investigated a wide range of migrating acyl substituents, neither steric, nor electronic, nor melting point factors, are responsible for controlling the rate of this solid-state rearrangement. A study of the crystal structures of a range of structurally diverse 1- and 2-acyl-3-aminoipyrazoles reveals that a non-Topochemical mechanism is operating and so the reactions are thought to take place at crystal defects. The reaction is observed not to occur throughout the bulk of the crystal when observed under a microscope and in addition the integrity of the crystal is not maintained throughout the reaction.