4-Ethynyl-1.3-dimethylpyrazole

With an activated C—C triple bond two successive additions can occur if the intermediate alkene is reactive enough. DMAD and 3,5-dimethylpyrazole give an initiaj fumarate (255) which reacts further at the other end to form regioselectively the succinates (256). On the other hand, methyl ethynyl ketone reacts twice at the same carbon atom with pyrazole to form 1,1-pyrazolylbutanone (258) (68ZC458). The probable intermediate, a pyrazolide vinylogue (257), can be prepared from methyl chlorovinyl ketone and pyrazole, in a reaction which is similar to acetylation (Section 4.04.2.1.3(x)). 

Cross-coupling of 5-ethynyl-4-chloro-l,3-dimethylpyrazole with 3-iodo-4-chloronitrobenzene was carried out in the presence of (PPh3)2PdCl2, Cul, and EtjN (66%) (96MC98) (Scheme 69). 

When 4-ethynyl-3,5-dimethylpyrazole interacts with bromine, only one halogen molecule is added, probably owing to steric hindrance (71TH1) (Scheme 78). 

In 1973, the unexpected transformation of 4-chloroethynyl-l,3,5-trimethylpy-razole under the action of sodium amide in liquid ammonia into 5-aminomethyl-4-ethynyl-l,3-dimethylpyrazole in 85% yield was reported (73IZV2166). Within... 

It should be notieed that N-unsubstituted 4-ehloroethynyl-3,5-dimethylpyrazole under the aetion of both NaNHa and -butyllithium leads only to 4-ethynyl-3,5-dimethylpyrazole (69IZV927) (Seheme 104). 

From 4-chloroethynyl-l,3-dimethylpyrazole 80% of 4-ethynyl-5-chloro-l,3-dimethylpyrazole was obtained. There is simultaneous formation of about 10% of 4-ethynyl-l,3-dimethylpyrazole (76IZV2148 77IZV2306) (Scheme 106). 

Attempts were made to perform heterocyclization with 4-phenylethynyl- and 4-ethynyl-5-aminomethyl-l,3-dimethylpyrazole where, on the one side, a strained six-membered ring can be formed, and, on the other side, the aliphatic amino group is more nucleophilic than the aromatic (Scheme 112). However, all attempts to cyclize the ethynylpyrazole and its phenyl analog failed (86TH1). 

For 1-ethynylpyrazole, l-ethynyl-3,5-dimethylpyrazole, l-ethynyl-3-methylpy-razole, and l-ethynyl-5-methylpyrazole, the ehemieal shifts of the methyne protons appear in CDCI3 at 3.14, 3.22, 3.05, and 3.21 ppm, respeetively (94AJC991). 

In the 4-substituted 1,3-dimethylpyrazoles with ethynyl group fixed in position 5, the acidity increases with a change in the character of substituents in the series H = NH2 < C CPh < I < Br = Cl. 

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