Heterocycles pyrazole

More recently, we have developed aromatic heterocyclic pyrazol-5-one-based tridentate N,N,0-donor ketiminate-supported magnesium and zinc benzyl-alkoxide systems [L2M2(p-OBn)2] where M = Mg 45 or Zn 46, and L = 4-... 

Later, Siddiqui et al. carried out the S5mthesis of novel heterocyclic pyrazole derivatives via heterocyclic 3-enaminones over NaHS04-Si02 catalysts under thermal solvent-free conditions [91]. The reaction was performed using an equimolar mixture of reactants at 343 K in absence of any solvent. 

The compounds of this article, ie, ftve-membered heterocycles containing two adjacent nitrogen atoms, can best be discussed according to the number of double bonds present. Pyrazoles contain two double bonds within the nucleus, imparting an aromatic character to these molecules. They are stable compounds and can display the isomeric forms, (1) and (2), when properly substituted. Pyrazoles are scarce ia nature when compared to the imidazoles (3), which are widespread and have a central role ia many biological processes. 

From Other Heteroeyeles by Rearrangement. Although there are numerous examples of pyrazole syntheses from other monocychc heterocycles by chemical, thermal, or photochemical means, such examples ate only of limited practical value on account of high cost. Reaction of diaziridinone (68) with the sodium salt of malondinitrile yields the di-/-butylaminopyrazolinone (69) (eq. 17) (45). 

There are several examples of the formation of pyridazines from other heterocycles, such as azirines, furans, pyrroles, isoxazoles, pyrazoles or pyrans and by ring contraction of 1,2-diazepines. Their formation is mentioned in Section 2.12.6.3.2. 

Hydrazino groups are also converted into H-compounds with mercury(II) oxide (74CR(C)-(278)427) in other reactions they have given hydrazones, or have been converted into pyrazoles and fused heterocyclic rings (77JAP(K)7785194), e.g. (72) -> (73). 

Details of bond lengths and bond angles for all the X-ray structures of heterocyclic compounds through 1970 are listed in Physical Methods in Heterocyclic Chemistry , volume 5. This compilation contains many examples for five-membered rings containing two heteroatoms, particularly pyrazoles, imidazoles, Isoxazoles, oxazoles, isothlazoles, thlazoles, 1,2-dlthloles and 1,3-dlthloles. Further examples of more recent measurements on these heterocyclic compounds can be found in the monograph chapters. 

Oxygen-containing rings can be opened by amines frequently this is followed by reclosure of the intermediate to form a new heterocycle. Thus isoxazoles containing electron-with-drawing substituents give pyrazoles with hydrazine, e.g. (183 Z = O) (183 Z = NH), and... 

The 3H- and 4//-pyrazoles and 2H- and 4//-imidazoles (83UP40200) contain two doable bonds in the heterocyclic ring, but in each case the conjugation does not include all the ring atoms hence the compounds are not aromatic. 

Use of mesoionic ring systems for the synthesis of five-membered heterocycles with two or more heteroatoms is relatively restricted because of the few readily accessible systems containing two heteroatoms in the 1,3-dipole. They are particularly suited for the unambiguous synthesis of pyrazoles as the azomethine imine is contained as a masked 1,3-dipole in the sydnone system. An attractive feature of their use is that the precursor to the mesoionic system may be used in the presence of the cyclodehydration agent and the dipolarophile, avoiding the necessity for isolating the mesoionic system. 

The excellent book by the late Professor T. J. Batterham contains all the available information (up to 1973) on pyrazoles and their non-aromatic derivatives (B-73NMR165) and on indazoles (B-73NMR263). The bibliography for pyrazoles and pyrazolones has been updated in (B-76MI40402). It should be emphasized that almost all the principal results about the H NMR spectra of these heterocycles were published at that time, and thus only a summary of the principal conclusions is needed here. 

IR and Raman studies of heterocycles today cover two different fields. For simple and symmetrical molecules very elaborate experiments (argon matrices, isotopic labelling) and complex calculations lead to the complete assignment of the fundamentals, tones and harmonics. However, the description of modes ought to be only approximate, since in a molecule like pyrazole there are no pure ones. This means that it is not correct to write that the band at 878 cm is y(CH), and the only correct assertion is that the y(CH) mode contributes to the band. On the other hand, IR spectroscopy is used as an analytical tool for identifying structures, and in this case, bands are assigned to r-iCO) or 5(NH) on the basis of a simple Nujol mull spectrum and conventional tables. Both atttitudes, almost antagonistic to each other, are discussed in this section. 

After the publication of a book on the prototropic tautomerism of aromatic heterocycles (76AHC(Sl)l) which covered the literature up to 1975, the study of the tautomerism of pyrazoles has not made great strides. In this section the main conclusions of this earlier review will be summarized and comments on a few recent and significant references added. 

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AHC(6)347). Heterocyclization of iV-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

Fused ring systems containing a pyrazole unit can be prepared either from the heterocyclic moiety by formation of a pyrazole ring or from the reaction between a pyrazole derivative and a suitably functionalized reagent. The ring systems thus obtained are discussed in detail in other chapters (Chapters 4.05, 4.35, 4.36) but it is of interest to discuss here those methods which start from a pyrazole derivative as the reactions involved can be considered as examples of the reactivity of pyrazoles. The most widely studied fused ring systems are the [5.6] systems and the examples described in this section will be chosen from this group and, occasionally, from [5.5] and [5.7] systems. 

This reactivity of A-unsubstituted amino-pyrazoles and -indazoles which can be regarded as 1,3-diamino derivatives has been used to build a great variety of fused six-membered heterocycles such as the 1,2,4-triazine derivatives (540) and (541), the 1,3,5-triazine derivatives (542) and (543), and benzothiadiazines (544). 

Pyrazoles can be prepared by ring opening reactions of fused systems already containing the pyrazole nucleus. Thus several [5.5], [5.6] and [5.7] fused heterocycles have been opened to substituted pyrazoles, usually in basic medium. In general, the method has little preparative interest since another pyrazole derivative has usually been used to build the ring-fused system. However, due to the unexpected structures obtained, two publications are worthy of notice. 6//-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine (638) was readily obtained from the corresponding pyrazolopyrimidine by the action of diazomethane at room temperature (Scheme 59) (81H(15)265). When (638) was treated with potassium hydroxide, the pyrazole (640) was formed, probably via the diazepine (639). 

Pyrazoles have been prepared by the action of hydrazines on heterocyclic derivatives which react as masked functional groups of a 1,3-difunctional derivative (Section 4.04.3.1.2(ii)). 

In this section formation of pyrazoles from the reaction of heterocycles with compounds other than hydrazines will be discussed. 

The stability of various heterocycles can be also compared using oxidation procedures. Thus, the oxidation of the heterocycles in Scheme 29 with potassium permanganate showed that under these reaction conditions the isoxazole ring is more stable than the furan ring but less stable than the pyrazole and furazan rings. 

Azocrown ethers pyrazoles, 5, 228 Azo dyes, 1, 328-331 colour and constitution, 1, 342 heterocyclic, 1, 325-326 Azo-hydrazone tautomerism, 1, 331, 334 Azoles acetic acids decarboxylation, 5, 92 acetoxymercurio reactions, 5, 107 acetyl... 

Cyclopent-2-en-l-one, 2-hydroxy-3-methyl-synthesis, 3, 693 Cyclopentenone, 4-methoxy-formation, 1, 423 Cyclopenthiazide as diuretic, 1, 174 Cyclopent[2,3-d]isoxazol-4-one structure, 6, 975 Cyclophane conformation, 2, 115 photoelectron spectroscopy, 2, 140 [2,2]Cyclophane conformation, 2, 115 Cyclophanes nomenclature, 1, 27 Cyclophosphamide as pharmaceutical, 1, 157 reviews, 1, 496 Cyclopiloselloidin synthesis, 3, 743 Cyclopolymerization heterocycle-forming, 1, 292-293 6H-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine pyrazoles from, 5, 285 Cydopropabenzopyran synthesis, 3, 700 Cyclopropachromenes synthesis, 3, 671 Cyclopropa[c]dnnolines synthesis, 7, 597 Cyclopropanation by carbenes... 

The aldehyde functionality present in 3-phenyl-2H-azirine-2-carbox-aldehyde reacts selectively with amines and with Qrignard and Wittig reagents to give a variety of substituted azirines. These azirines have been used, in turn, to prepare a wide assortment of heterocyclic rings such as oxazoles, imidazoles, pyrazoles, pyrroles, and benzazepins. ... 

The classical age of preparative organic chemistry saw the exploration of the extensive field of five-membered heterocyclic aromatic systems. The stability of these systems, in contrast to saturated systems, is not necessarily affected by the accumulation of neighboring heteroatoms. In the series pyrrole, pyrazole, triazole, and tetrazole an increasing stability is observed in the presence of electrophiles and oxidants, and a natural next step was to attempt the synthesis of pentazole (1). However, pentazole has eluded the manifold and continual efforts to synthesize and isolate it. 

Some reviews relevant for this section concern N CPMAS [86AG(E)383] of pyrazoles, including CPMAS results (93MRC107) and proton transfer in solid heterocycles (94JHC695). The most relevant studies reported in Table X are (1) the use of C CPMAS NMR to identify... 

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