Pyrazole, 4- Subject

Other pyrazole derivatives have not been the subject of systematic studies. Owing to the variety of structures involved, figures instead of tables are used to describe chemical shift... 

After these findings, evidence was presented that pyrazoles which crystalline as cyclic dimers 9a/9b and tetramers 11a are subject to double and quadruple proton transfers respectively (92JA9657 95JOC1965). An im-... 

The final chapter in this volume by Alexander Sadimenko (University of Fort Hare, South Afiica) continues a series by this author on the organometaUic chemistry of heterocycles, of which 0,S monoheterocycles and N,P,Si,B monoheterocycles were published in volumes 78 and 79, respectively. The organometaUic chemistry of pyrazole is so broad that the present overview does not include the polyfunctional, chelating frameworks containing pyrazolyl units, which are typified by the pyrazolyl borate derivatives. These will be the subject of a future chapter. 

The reaction of disubstituted diacetylenes with hydrazine hydrate was reported by Darbinyan et al. (70AKZ640). In the first stage the addition of hydrazine to the terminal carbon atom of the diacetylene system is analogous to that of primary amines to diacetylene (69ZC108 69ZC110). With monosubstituted diacetylenes (R = H), hydrazine adds to the terminal triple bond. This leads to the formation of vinylacetylenic hydrazine 22 which cyclizes to dihydropyrazole 23 subjected to further isomerization to the pyrazole 25. It is possible that hydrazine 22 undergoes hydration to the ketone 24 which can easily be cyclized to the pyrazole 25... 

The groups of Giacomelli and Taddei have developed a rapid solution-phase protocol for the synthesis of 1,4,5-trisubstituted pyrazole libraries (Scheme 6.194) [356]. The transformations involved the cyclization of a monosubstituted hydrazine with an enamino-/8-ketoester derived from a /8-ketoester and N,N-dimethylformamide dimethyl acetal (DMFDMA). The sites for molecular diversity in this approach are the substituents on the hydrazine (R3) and on the starting j3-keto ester (R1, R2). Subjecting a solution of the /8-keto ester in DMFDMA as solvent to 5 min of microwave irradiation (domestic oven) led to full and clean conversion to the corresponding enamine. After evaporation of the excess DMFDMA, ethanol was added to the crude reaction mixture followed by 1 equivalent of the hydrazine hydrochloride and 1.5 equivalents of triethylamine base. Further microwave irradiation for 8 min provided - after purification by filtration through a short silica gel column - the desired pyrazoles in >90% purity. 

In a new twist on this subject, electrochemical activation parameters have been obtained for two series of redox couples that undergo coupled spin-state change and electron transfer (28). One series is [M(tacn)2]3+/2+ where M = Fe, Co, Ni, and Ru, and tacn = 1,4,7-triazacyclononane. The other is [Fe(pzb)2]+/0, where pzb-= hydrotris(pyrazol-l-yl)borate... 

This chapter is an update to Chapter 8.04 of CHEC-II(1996) <1996CHEC-II(8)95> it covers the literature from 1995 to 2007. More specifically, it contains major informations on the preparation and reactivity of these bicyclic 5-5 systems. Furthermore, a variety of biological activities and important applications in the chemical, medical, and agrochemical field beyond the scope of this chapter. Considering the little information obtained in few areas, coverage of sections dealing with structural, theoretical and thermodynamic data has been kept to a minimum since only imidazo[l,2- ]imidazole and imidazo[l,2- ]pyrazole systems have been the subject of recent studies. The most important structural data have already been summarized in CHEC-II(1996), Chapter 8.04. 

Electrophilic cyclodimerization (to 26) also results when (25) is subjected to Bischler-Napieralski conditions (POCI3, reflux), presumably through reaction of pyrazole with the imino chloride intermediate (78JHC1339). 

As was pointed out in the preceding chapter,1 pyrazoles are known in two nonaromatic forms (the 3H- and 4//-pyr azoles, Scheme 1) in addition to the more familiar aromatic 1H form. The 3//-pyrazoles, which may be considered as cyclic vinylazo compounds, have been discussed in reference I the 4//-pyrazoIes, which are cyclic azines, are the subject of this review. 

Of commercial interest are benzo- and other fused aromatic 1,2,3-diazaborine derivatives which have exhibited good antibacterial activity against a variety of microorganisms (155—157). The reaction of pyrazole or C-substituted pyrazoles with boranes yields the pyrazabole system, a class of exceptionally stable compounds. More than 70 species in this system have been reported and the subject comprehensively reviewed (158). These compounds have been used as ligands in transition-metal complexes (159). 

The 2-alkyl- or aryl-substituted pyrazole 1-oxides are usually stable, crystalline, semipolar, and slightly hygroscopic compounds. 2-Substituted pyrazole 1-oxides are weak bases, being subject to protonation at the negatively charged oxygen atom. 2-Hyd roxypyrazole 1-oxides 74 (R = OH) are acids, no pf(a values seem to have been reported. 

Abstract Synthesis methods of various C- and /V-nitroderivativcs of five-membered azoles - pyrazoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles, oxazoles, oxadiazoles, isoxazoles, thiazoles, thiadiazoles, isothiazoles, selenazoles and tetrazoles - are summarized and critically discussed. The special attention focuses on the nitration reaction of azoles with nitric acid or sulfuric-nitric acid mixture, one of the main synthetic routes to nitroazoles. The nitration reactions with such nitrating agents as acetylnitrate, nitric acid/trifluoroacetic anhydride, nitrogen dioxide, nitrogen tetrox-ide, nitronium tetrafluoroborate, V-nitropicolinium tetrafluoroborate are reported. General information on the theory of electrophilic nitration of aromatic compounds is included in the chapter covering synthetic methods. The kinetics and mechanisms of nitration of five-membered azoles are considered. The nitroazole preparation from different cyclic systems or from aminoazoles or based on heterocyclization is the subject of wide speculation. The particular section is devoted to the chemistry of extraordinary class of nitroazoles - polynitroazoles. Vicarious nucleophilic substitution (VNS) reaction in nitroazoles is reviewed in detail. 

Despite the multitude of well characterized boron compounds, the knowledge of azole derivatives of boron is still rather limited. For example, only three C-borylated pyrazoles are known. Although N-borylated pyrazole derivatives are considerably more abundant, until most recently these were restricted to compounds containing only four-coordinate boron. Of these, the poly(l-pyrazolyl)borate anions have been a bonanza for the coordination chemist, since the steric and electronic features of these ions render them as extremely useful (polydentate and chelating) ligands. However, recent studies of the chemistry of boron derivatives of pyrazoles have provided for some noteworthy developments and a survey of such compounds and their chemistry appears to be a timely subject. 

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. 

AMI semiempirical calculations have shown that, as far as tautomerism is concerned, there is a structural relationship between jS-dicarbonyl compounds and NH-pyrazoles, and in a wide variety of NH-pyrazoles studied " the most stable tautomer was found to be that having the largest single-bond character between the C(3)—C(4) bond. The problem of proton transfer in NH-pyrazole crystals has been subjected to a detailed theoretical study, while a study of the tautomerism of 2-aryl and 2-heteroaryl derivatives of benzimidazole has indicated that tautomerism takes place by the intermolecular relay of protons between stacked molecules. The first report of the stable co-existence of two different histidine tautomers in one peptide crystal structure has appeared. Ab initio calculations have been used to study the tautomerism of both histamine and pyrazolo[3,4-i/]pyridazine in the gas phase and in aqueous solution, and a theoretical study of the NH tautomerism in free-base porphyrin has been undertaken. ... 

Whereas pyrazoles are quite readily iV-nitrated by nitric acid in acetic anhydride or with nitronium fluoroborate, imidazoles are usually far too basic, and give the nitrate salts instead. A nitro substituent, however, decreases the basicity sufficiently to allow iV-nitration to occur. The A -nitro compounds are subject to thermal rearrangement to the 2- and 4-nitro isomers, pointing to an alternative route to such compounds [63]. 

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