Novel polyfluoroalkylated pyrazoles from 2-polyfluoroacylcycloalkanones and hydrazines: syntheses and unequivocal molecular structure assignment

Abstract

The reaction between 2-trifluoroacetylcycloalkanones and methylhydrazine or phenylhydrazine exclusively yields 3-CF3-pyrazoles. When the chain length of the polyfluorinated substituent in RFC(O) group increases, 5-RF-pyrazoles are isolated. The reaction of 2-trifluoroacetylcyclohexanone with 2-hydrazinopyradine gives 5-hydroxypyrazoline, an intermediate in the formation of 5-CF3-pyrazoles. The regiochemistry of the condensation is probably controlled by the nucleophilicity of the terminal nitrogen in the mono substituted hydrazines and by the steric requirements of the RF group in the 1,3-diketones. Polymethylene chain containing pyrazoles obtained from the 1,3-diketones in question and hydrazine prefer the 3-RF tautomeric form, irrespective of carbocyclic ring size and polyfluoroalkyl group chain length.Key words: polyfluorinated 1,3-diketones, hydrazines, isomeric pyrazoles, molecular structure.

Trifluoromethyl‐β‐dicarbonyls as Versatile Synthons in Synthesis of Heterocycles

“…Sevenard et al studied the regioselectivity of condensation of 2-polyfluoroacylcycloalkanones 80 containing electronic and steric inequivalence of the electrophilic centers with hydrazine and monosubstituted hydrazines. [106] In the reaction of 2trifluoroacetylcycloalkanones 80 with methylhydrazine or phenylhydrazine 54 in refluxing methanol, NH 2 group attacked COCF 3 group followed by subsequent cyclization to give 3-CF 3pyrazoles 81 as the exclusive products. As the polyfluorinated substituent in 1,3-diketones becomes longer, reaction yielded 5-CF 3 -pyrazoles 82 (Scheme 22).…”

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

“…Although numerous syntheses of pyrazolines [3–5] in general and 1-acyl-5-hydroxypyrazolines [24–26] specifically have been published employing a cyclizing addition of an acylhydrazone to the carbonyl group as a ring-forming reaction [32–40], their diversity-oriented one-pot synthesis in a multicomponent approach has remained unexplored to date. In the course of our program directed to develop multicomponent syntheses of heterocycles by transition-metal catalysis [41–42] we conceptualized catalytic entries to alkynones and alkynediones as suitable intermediates in addition–cyclocondensation syntheses of numerous heterocycles, which can indeed be prepared by consecutive multicomponent reactions [43–47].…”

Regioselective Preparation of Saturated Spirocyclic and Ring-Expanded Fused Pyrazoles

“…Saturated bicyclic pyrazoles are typically prepared by the Knorr condensation of a hydrazine derivative with a 1,3-dicarbonyl compound − ,− (Scheme a) or an equivalent substrate. ,− Alternative procedures involve variations of the 1,3-dipolar cycloaddition (Scheme b). − ,− The main drawback of these methods lies in the often laborious preparation of the required starting materials, which can limit the available functionality in the product and precludes the late-stage introduction of structural diversity. In addition, some saturated heterocyclic systems have been noted to give unexpected rearrangement products under Knorr condensation conditions …”