Synthesis of pyrazoles

This review summarizes the synthesis of various pyrazoles reported by us and some other research groups in 1981–1989.     

5-Fluoro-substituted pyrazoles

A preparative method was developed for the synthesis of 5-fluoro-substituted pyrazoles by the reaction of fluoroolefins with substituted hydrazines in the presence of triethylamine. The fluorine atom at the C₅ position of the pyrazoles obtained is readily substituted by O-, N-, and S-nucleophiles with the formation of 5-alkoxy-, amino-, mercapto-substituted fluoroalkylpyrazoles.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2583–2589, November, 1990.     

Efficient one-pot synthesis of substituted pyrazoles

An efficient, one-pot synthesis of substituted pyrazoles from enones, hydrazides, and halides was developed. In comparison with the classical Knorr pyrazole synthesis, this methodology gave a different type of product (R³≥R⁵). A range of substituted pyrazoles were prepared in good to high yields with complete regioselectivity.     

Studies on pyrazoles

A new method has been developed for the synthesis of N-vinylpyrazoles from pyrazoles not substituted at the nitrogen atom. This synthesis is accomplished by the action of vinyl acetate and is catalyzed by mercuric sulfate.For part LIX, see [1].     

Diversity-orientated synthesis of 3,5-bis(arylamino)pyrazoles

The synthesis of differentially-substituted 3,5-bis(arylamino)pyrazoles has not yet been documented. During our investigation, we managed to develop a novel, entirely combinatorial synthesis of 3,5-bis(arylamino)pyrazoles relying on a simple one-pot two-step operation.     

Zinc-catalyzed synthesis of pyrazolines and pyrazoles via hydrohydrazination

A novel regioselective synthesis of aryl-substituted pyrazolines and pyrazoles has been developed. Substituted phenylhydrazines react with 3-butynol in the presence of a catalytic amount of zinc triflate to give pyrazoline derivatives. The resulting products are easily oxidized in a one-pot procedure to the corresponding pyrazoles.     

Regioselective synthesis of 1-aryl-3,4-substituted/annulated-5-(methylthio)pyrazoles and 1-aryl-3-(methylthio)-4,5-substituted/annulated pyrazoles

[reaction: see text] Highly efficient and regioselective synthesis of 1-aryl-3,4-substituted/annulated-5-(methylthio)pyrazoles and 1-aryl-3-(methylthio)-4,5-substituted/annulated pyrazoles has been reported via cyclocondensation of arylhydrazines with either alpha-oxoketene dithioacetals or beta-oxodithioesters.     

One-pot three-component synthesis of pyrazoles through a tandem coupling-cyclocondensation sequence

An efficient and general one-pot procedure for the synthesis of pyrazoles from acid chlorides, terminal alkynes and hydrazines was described via a coupling and cyclocondensation sequence. Acid chlorides coupled with terminal alkynes to give α,β-unsaturated ynones, and in situ converted into pyrazoles by the cycloaddition of hydrazines. The desired pyrazoles were obtained with 15-85% isolated yields.     

Straightforward transformation of isoxazoles into pyrazoles: renewed and improved

Isoxazoles bearing alkyl or carbamoyl groups were transformed into the corresponding pyrazoles in high yields by the treatment with hydrazine in methanol in the presence of a hydrogenation catalyst, e.g., Raney nickel, at ambient temperature. For the synthesis of N-substituted pyrazoles, hydrogenolysis of isoxazole followed by the treatment with substituted hydrazine was required. 3(5)-Aryl- or acylamido-substituted isoxazoles are less suitable for such transformations.     

Synthesis of novel pyrazoles via [2+3]-dipolar cycloaddition using alkyne surrogates

The syntheses of an important class of hitherto unreported novel pyrazoles are described. The regioselective synthesis of 1,3,4,5-tetrasubstituted pyrazoles was achieved by the Huisgen cyclization of nitrile imines with a trisubstituted bromoalkene. The substituted bromoalkene functions as an alkyne synthon which was used to construct 5,5-disubstituted bromopyrazoline intermediates that undergo aromatization to the analogous pyrazoles through the loss of HBr. The cycloaddition regioselectivity was confirmed through single X-ray crystal data of one of the pyrazoles.     

One-pot synthesis of 5-(substituted-amino)pyrazoles

An efficient and mild one-pot synthesis of substituted 5-alkylamino and/or 5-(arylamino)pyrazoles is described. A suitably decorated β-ketoamide, an aryl or alkyl hydrazine and Lawesson's reagent are suspended in THF/Py and gently heated to yield the requisite 5-aminopyrazoles.     

Synthesis of tetra-substituted pyrazoles

A set of highly substituted pyrazoles bearing different functional groups on the pyrazole core was developed. Employing a suitable protecting group strategy we could regioselectively introduce various substituents in position 1, 3 and 4 of the pyrazole. This enabled the synthesis of various derivatives of a pyrazole–biscarboxamide with insecticidal activity. During the optimization process we focused on the precise exchange of carboxamide as well as other functional groups based on the concept of bioisosterism.     

Solid-phase synthesis of 5-substituted amino pyrazoles

An efficient method for the solid-supported synthesis of 5-N-alkylamino and 5-N-arylamino pyrazoles is described. This method is general and mild and utilizes readily accessible resin-immobilized beta-ketoamides 2 as starting materials for the preparation of 1. Resin-immobilized beta-ketoamide, aryl-, or alkylhydazine and Lawesson's reagent are suspended in a mixture of THF/Py and heated at 50-55 degrees C to give a resin-bound 5-aminopyrazole, that is liberated from the solid support by treatment with TFA.     

Synthesis of substituted pyrazoles via tandem cross-coupling/electrocyclization of enol triflates and diazoacetates

The synthesis of 3,4,5-trisubstituted pyrazoles via a tandem catalytic cross-coupling/electrocyclization of enol triflates and diazoacetates is presented. The initial scope of this methodology is demonstrated on a range of differentially substituted acyclic and cyclic enol triflates as well as an elaborated set of diazoacetates to provide the corresponding pyrazoles with a high degree of structural complexity.     

Synthesis of diversely 1,3,5-trisubstituted pyrazoles via 5-exo-dig cyclization

5-Exo-dig cyclocondensation of alk-3-yn-1-ones with hydrazines, in the presence of montmorillonite K-10, provides an effective method with a high atom economy for the synthesis of diversely 1,3,5-trisubstituted pyrazoles. The microwave-accelerated reaction proceeds in the absence of solvent and leads to 5-benzyl substituted pyrazoles with good yields (72-91%). The regiochemistry of the process was confirmed by the X-ray crystallographic structure determination of 1-(2-fluorophenyl)-5-(4-methylbenzyl)-3-phenyl-1H-pyrazole.     

Functionalization of NH-unsubstituted androstano[17,16-d]pyrazoles. Synthesis of 2-arylamino-2-thioxoacetylandrostano[17,16-d]pyrazoles

Russian Chemical Bulletin - An approach to the synthesis of earlier unknown androstano[17,16-d]pyrazoles containing a monothiooxamide fragment at the nitrogen atom of the pyrazole ring has been...     

Regioselective palladium-catalyzed CH arylation of 4-alkoxy and 4-thioalkyl pyrazoles

A methodology for the palladium-catalyzed regioselective CH arylation of electron rich pyrazoles has been developed. New ligands and mild conditions (70–90?°C) have been identified for this transformation. An intramolecular application of the methodology provided a novel synthetic route for the regioselective synthesis of 1,5-dihydroisochromeno[4,3-c]pyrazoles and 1,5-dihydroisothiochromeno[4,3-c]pyrazoles.     

Conjugate base catalysed one-pot synthesis of pyrazoles from β-formyl enamides

A novel one-pot synthesis of pyrazoles has been accomplished by the reaction of β-formyl enamides with hydroxylamine hydrochloride catalysed by potassium dihydrogenphosphate in acid medium.     

The Structure of N‐phenyl‐pyrazoles and Indazoles: Mononitro,Dinitro, and Trinitro Derivatives

This review explores the heterocyclic family of N‐nitrophenyl pyrazoles and indazoles covering mainly their structural aspects, with special emphasis on the X‐ray diffraction data. NMR spectroscopy and the theoretical calculations will also be briefly summarized. The synthesis and reactivity aspects will be reported when they are specific to these compounds.     

Fully automated polymer-assisted synthesis of 1,5-biaryl pyrazoles

The polymer-assisted solution-phase (PASP) synthesis of a 192-member 2-D array of 1,5-biaryl pyrazoles 4[1-12,1-16] is reported. The synthesis was performed in a fully automated manner using a multiprobe top-filtration robot and incorporates a "catch and release" step to afford library compounds directly in high yield and purity.