Synlett 2014; 25(3): 453-454
DOI: 10.1055/s-0033-1340469
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© Georg Thieme Verlag Stuttgart · New York

1-Cyanoacetyl-3,5-dimethylpyrazole

Elena A. Chigorina
Chemical Diversity Research Institute, 2a Rabochaya Street, ­Khimki, Moscow Region, 141400, Russian Federation   Email: echigorina@mail.ru
› Author Affiliations
Further Information

Publication History

Publication Date:
12 December 2013 (online)

Introduction

1-Cyanoacetyl-3,5-dimethylpyrazole (1) is a white crystalline solid with a melting point of 118–121 °C,[1] stable at room temperature in air. In the 1950s, Ried and Meyer[1] were the first to describe it as a mild cyanoacetylating reagent, being more reactive than ethyl cyanoacetate. Pyrazole 1 is a cheap, handy, and non-toxic reagent that proved to be superior to cyanoacetyl chloride and cyanoacetyl azide in terms of stability and convenience. It is commercially available and can be prepared in about 90% yield by condensation of acetylacetone (2) with cyanoacetohydrazide (3) in aqueous hydrochloric acid (Scheme [1]).[2]

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Scheme 1 Preparation of 1-cyanoacetyl-3,5-dimethylpyrazole

The first and most common application of 1-cyanoacetyl-3,5-dimethylpyrazole (1) is the synthesis of N-substituted cyanoacetamides, which are known as versatile building blocks for heterocyclic synthesis.[3] [4] 1 readily reacts with various N-nucleophiles (amines, hydrazines, hydrazides, semicarbazides) in an inert solvent (ether, benzene, toluene, dioxane) under mild conditions.

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Scheme 2 Synthesis of s-substituted cyanoacetamides

The N-cyanoacetylation products can be isolated from the reaction mixture in crystalline form, while the 3,5-dimethylpyrazole by-product remains in the mother liquor. The yields are usually high and sometimes nearly quantitative.

 
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