Pyrazoles with acetylenic esters

The reactions of sydnones with acetylenic esters are generally thermally induced concerted processes which are allowed on orbital symmetry considerations.8 On the basis of Huisgen s mechanistic study,805 the conversion of 71 into 73 proceeds through the formation of 72 in a slow rate-determining step, followed by rapid loss of carbon dioxide, giving the pyrazole 73. 

Diazopropyne reacts similarly with a monosubstituted acetylene to form 3(5)-alkynylpyrazoles (68LA113). Thus, the reaction of diazopropyne with acetylene-carboxylic acid methyl ether results in 5-ethynyl-l//-pyrazole-3-carboxylic acid methyl ether in 48 h in 62% yield. 5-Ethynyl-l//-pyrazole-3,4-dicarboxylic acid dimethyl ester was prepared by reaction of diazopropyne with acetylenedicar-boxylic acid methyl ether (Scheme 10). 

Sydnones behave as 1,3-dipolar systems and undergo addition reactions with various dipolarophiles. Huisgen, Grashey, Gotthardt, and Schmidt503,504 were the first to react acetylenic esters with sydnones and obtained pyrazoles e.g., 71 with DMAD (1 hour, 120°, in xylene) gave 99% of the pyrazole 73. These reactions have also been carried out with propiolic and phenylpropiolic esters, and their kinetics have been studied.505... 

Acetylenecarboxylic esters, reactions with nitrogen-containing heterocycles, 23, 263 Acetylenic derivatives of pyrazoles, synthesis and properties of, 82, 1 Acetylenic esters, synthesis of heterocycles through nucleophilic additions to, 19,297 Acid-catalyzed polymerization of pyrroles and indoles, 2, 287... 

A-Methyl-/V-nitroso-a-(trimethylsilyl)benzylamine reacts thermally with DMAD to give 3,4-dicarbomethoxy-l-methyl-lH-pyrazole. The reaction is highly sensitive to the temperature upon increasing the temperature from 25 to 110 °C, the reaction time drops from 168 h to 3 min and yields increase from 30 to 100%. No reaction occurs from non-silylated /V-methyl-/V-nitrosobenzylamine. Other acetylenic esters have been successfully tested. In contrast, phenylacetylene gives a poor yield of the adduct and diphenylace-tylene does not react.473... 

Pyrazole derivatives can be prepared analogously from alkynes e.g., reaction of propynal with ethereal diazomethane gives 84% of pyrazole-3-carbaldehyde and that with diazoacetic ester gives 86% of ethyl 5-formyl-pyrazole-3-carb-oxylate.18 Further, pyrazole itself is readily accessible from acetylene and diazomethane.19... 

During the preparation of 3-pyrazolyl C-nucleosides from aldose hydra-zonoyl halides (282) and acetylenic esters (Section VII,B,I Scheme 61), Tronchet et al. isolated the 3,6-diglycosyl-l,2,4,5-tetrazine C-nucleoside 1084 in 30% yield together with the pyrazol-3-yl C-nucleosides 248 and 285 (72HCA2121 76MI8) (Scheme 316). 

Trimethyllead diazoacetic acid ethyl ester reacts with activated alkenes or acetylenes to provide organolead pyrazoles or pyrazolines197 ... 

A useful route to a,/(-acetylenic acids, illustrated by the preparation of but-2-ynoic acid (Expt 5.217), involves the base-induced decomposition of the dibromopyrazolone which is obtained by brominating pyrazol-5-one, which is itself prepared by the reaction of a / -keto ester with hydrazine. 

Besides processes (1) and (2), the reader should be aware that nucleophilic attacks on alkynes are treated in other chapters of this book, dealing with rearrangements, cyclizations, polyacetylenes, cyclic acetylenes and perhaps others. A number of publications overlap with ours in different ways and at different levels -. They treat individual alkynes or families " , e.g. acetylene, diacetylenes , acetylene dicarboxylic esters haloacetylenes , alkynyl ethers and thioethers > ynamines , fluoro-alkynes ethynyl ketpnes , nitroalkynes , etc. synthetic targets, e.g. pyrazoles , if-l,2,3-triazoles , isothiazoles , indolizines S etc. reagents, e.g. nitrones , lithium aluminium hydride , heterocyclic A -oxides - , azomethine ylids - , tertiary phosphorus compounds , miscellaneous dipolar nucleophiles - , etc. The reader will appreciate that all of these constitute alternate entries into our subject. 

Af-Unsubstituted pyrazoles and indazoles add to compounds containing activated double and triple bonds (67HC 22)1,B-76MI40402>. Amongst C—C double and triple bonds, maleic anhydride, acrylic acid esters and nitriles, acetylene-carboxylic and -dicarboxylic esters (78AHC(23)263), quinones, and some a,/3-unsaturated ketones have been used with success. Phenylacetylene reacts with pyrazole in the presence of Na/HMPT as catalyst to yield the Z isomer of 1-styrylpyrazole in a highly stereoselective reaction (78JHC1543). 

Syntheses and properties of acetylenic derivatives of pyrazoles 02AHC(82)1. Syntheses of 2-pyrazolines by the reactions of a,/ -unsaturated aldehydes, ketones, and esters with diazoalkanes, nitrile imines, and hydrazines 02JHC1. 

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