Acetylene pyrazoles

B.p. about 0°. Very poisonous. Powerful methylating agent. HCl — >- CHgCl. I —> CHgIg. HCN —> acetonitrile. Acetylene—pyrazole. Acids —> methyl esters. Phenols —> methyl ethers. 

An unusual 1,4-migration of a trifluoromethyl group was observed when azomethine imines were synthesized from hexafluoroacetone azine and alkoxy-acetylenes The rearrangement, which occurs at temperatures as low as 0 "C, results in the formation of A-(perfluoro-ferf-butyl)pyrazoles [207] (equation 46)... 

The 3,5-bis(trifluoromethyl)pyrazolate analog [Ir(cod)(/x-3,5-(CF3)2pz)]2 does not enter into oxidative addition with iodine, methyl iodide, or acetylenes. The mixture of pyrazolate and 3,5-bis(trifluoromethyl)pyrazolate gives [(rj -codllrf/x-pz)(/L-3,5-(CF3)2pz)Ir(rj -cod)], which reacts with bis(trifluoromethyl)acetylene in a peculiar manner [83JCS(CC)580], producing 145, where 3,5-bis(trifluoromethyl) pyrazolate is replaced by the ethylene bridge and the rj -coordination mode of one of the cod ligands is converted into the rj -allylic mode. 

Dipolar additions of diazomethane to acetylenes under mild conditions are restricted to monosubstituted acetylenes thus the formation of pyrazole derivatives 1 (1,3-dipolar addition, C=C isomerization, then methylation) confirms the existence of a terminal acetylene in caryoynencins (87TL3981) (Scheme 5). 

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). 

The above method can also be used to simultaneously transform two acetyl groups into acetylenic ones in positions 3 and 5 of the pyrazole ring. This is demonstrated by the synthesis of 3,5-diethynyl- 1-methylpyrazole (yield 62%) from 3,5-diacetyl-1-methylpyrazole (Scheme 30). 

Examples of dehydrobromination leading to bromoethynylpyrazoles as illustrated by Scheme 36 are described in a patent (99USP5925769). Treatment of 1,1-dibromooleflns with tetrabutylammonium fluoride in THE at room temperature for about 24 h under N2 gives the l-bromo-2-(pyrazol-3-yl)acetylenes where R, R, R, and R" are independently selected from H and alkyl, alkoxy. 

To ascertain the possibility of inserting more than one acetylenic moiety into the pyrazole ring, the replacement of two and three iodine atoms in the appropriate halides by different alk-l-ynes was carried out. To increase the total rate, the cross-coupling of diiodopyrazoles and triiodopyrazole was performed with higher initial concentrations of the reactants than for the monoiodides. The reaction of diiodopyrazoles with the acetal was completed for the most part in 40 h, and in 64 h in the case of triiodopyrazole. The yields of the di- and triacetals reached 70-90% (Table XTTT). 

There are slight differences in the reactivity of the acetylenic groups depending on their position in the pyrazole ring. This can be followed using py-razole diethynyl derivatives as an example. In the case of 4,5-diethynyl- and... 

The triple bond in pyrazole derivatives gives, as do other acetylene derivatives, typical addition reactions. 

In recent years, trimethylsilyl protection has often been used for the methine proton of the acetylenic group because of the mild reaction conditions for desilylation. As a rule, the starting pyrazole trimethylsilyl derivative is mixed up, at room temperature, with a 2 A aqueous solution of NaOH, potash, or methanol solution in ammonia. 

Trimethylsilylethynylpyrazole was deprotected by treatment with tetrabutyl-ammonium fluoride (TBAF) to give monosubstituted acetylene in 90% yield. (96ADD193). The same conditions were used to cleave the trimethylsilyl group in l-tetrahydropyranyl-3-carboxyethyl-4-[2-(trimethylsilyl)ethynyl]pyrazole (96INP 9640704). 

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