Acetylenic derivatives of pyrazoles, synthesis

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... 

S. F. Vasilevsky and E. V. Tetryakov (Novosibirsk, Russia), together with J. Elguero (Madrid, Spain), have summarized the synthesis, chemical and spectroscopic properties, and biological activity of acetylenic derivatives of pyrazoles, a field which has shown explosive growth in the past few years. 

S. F. Vasilevsky Synthesis and properties of acetylenic derivatives of pyrazoles 2002AHC1... 

Vasilevsky, S.F., Tretyakov, E.V. and Elguero, J. (2002) Synthesis and properties of acetylenic derivatives of pyrazoles, in Advances in Heterocyclic Chemistry, vol. 82 (ed. A.R. Katritzky), Elsevier, New York-London, pp. 1-99. 

PECHMANN PYRAZOLE SYNTHESIS. Formation of pyrazoles from acetylenes and diazomethane. The analogous addition of diazoacetic esters to the triple bond yields pyrazolecarboxylic acid derivatives. 

Pentafluorosulfanyl acetylene is a useful starting reagent for the synthesis of a variety of SF5 derivatives of saturated ethers, vinyl ethers, pyrazoles, cyclic alkenes, and alkyl-substituted phenyl-sulfur pentafluorides (134). It is also used for the preparation of a number of F5S-containing alkenes and alkynes (138, 139). 

The original reaction discovered by Pechmann involved the cycloaddition of diazomethane and acetylene. Although a better understanding of the reaction has led to the common use of more electron-deficient alkynes, diazomethane continues to be synthetically useful. A recent elegant example of the use of diazomethane as the 1,3-dipole was demonstrated in the preparation of 2,3-benzodiazepine derivatives as potential non-competitive AMPA antagonists. " Beginning with the alkyne, the pyrazole moiety could be incorporated into the benzodiazepine structure, using the Pechmann pyrazole synthesis, to produce the 2,3-benzodiazepines. 

A mixture of 2-iodopyridine, phenylacetylene, activated Cu-powder, and anhydrous K2CO3 in dimethylformamide stirred 5 hrs. at 140 under Ng -(phenyl-ethynyl)pyridine. Y 88%. F. e., also with protection of alcohol groups as a-ethoxyethyl ethers (cf. Synth. Meth. 20, 22), s. M. S. Shvartsberg et al., Izvest. 1970, 1144 Eng. Transl. 1079 pyrazole derivs. s. Izvest. 1971, 1764 C. A. 75, 151724 in pyridine, prepn. of ethynylbenzenes s. ibid. 1971, 1306 C. A. 75, 88219 aliphatic acetylene derivs. with /i-butyllithium in the presence of hexamethyl-phosphoramide s. M. Schwarz and R. M. Waters, Synthesis 1972, 567. 

Propiolaldehyde diethyl acetal has found numerous synthetic applications in the literature which may be briefly summarized. The compound has been utilized in the synthesis of unsaturated and polyunsaturated acetals and aldehydes by alkylation of metal-lated derivatives, " by Cadiot-Chodkiewicz coupling with halo acetylenes, " and by reaction with organocuprates. Syntheses of heterocyclic compounds including pyrazoles, isoxazoles, triazoles, and pyrimidines have employed this three-carbon building block. Propiolaldehyde diethyl acetal has also been put to use in the synthesis of such natural products as polyacetylenes " and steroids. ... 

Phosphazenes, derived from hydrazines and acetylenic esters, were employed in the regioselective synthesis of 5-pyrazolones and pyrazoles <1999T14451>. Reactions of isocyanides 637 and dialkyl acetylenedicarboxylates 638 in the presence of 1,2-diacylhydrazines 639 led to highly functionalized pyrazolines 640 (Equation 133) <2005TL6545>. 

The branched-chain acetylenic sugar derivative (380) reacted with aliphatic and aromatic aldehydes in the presence of a strong base to give the alkynols (381) and the enones (382), respectively. The synthesis of analogues of (381) and the conversion of the analogues into substituted pyrazole derivatives are referred to" " in Chapter 9. 

Heterocyclic acetylenes also worked very well. Alkynes bearing on the backbones of quinoline, isoquinoline, benzothiophene, benzofuran, dibenzofiuan, and pyrazole were converted to heterocyclic nitriles (109-114) in 63-86 % yields. Interestingly, this nitrile synthesis could be applied to natural product derivatives. For example, the alkynyl ester of Vitamin E gave nitrile 115 in 45 % yield (in 80 % yield based on recovered starting material) the alkynyl ester of oleic acid gave nitrile in 68 % isolated yield. 

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