Pyrazole, aromaticity Reviews

A book (B-71MS) and a review by Nishiwaki (74H(2)473) contain much information about the behaviour of pyrazoles under electron impact. The Nishiwaki review covers mainly the hydrogen scramblings and the skeletal rearrangements which occur. One of the first conclusions reached was that pyrazoles, due to their aromatic character, are extremely stable under electron impact (67ZOR1540). In the dissociative ionization of pyrazole itself, the molecular ion contributes about 45% to the total ion current thus, the molecular ion is the most intense ion in the spectrum. 

Since aromaticity is, at best, a relative value, the problem of the aromaticity of pyrazole, compared to other azoles, is to be found in Section 4.01.1.2, in which the authoritative review by Cook et al. (74AHC(17)255) is summarized. 

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. 

Porphyrin, 5,10,15,20-tetraphenyl-, 4, 386 Porphyrin, vinyl-synthesis, 4, 278, 279 Porphyrin coenzymes in biochemical pathways, 1, 258-260 Porphyrinogen, mcso-tetraaryl-synthesis, 4, 230 Porphyrinogens, 4, 378, 394 pyrazoles, 5, 228 synthesis, 4, 231 Porphyrins, 4, 377-442 acetylation, 4, 395 aromatic ring current, 4, 385 basicity, 4, 400 biosynthesis, reviews, 1, 99... 

Sulfur. Thiophene and benzo[ >] thiophene are both aromatic heterocycles, as discussed earlier in this review. Isothiazole is a planar molecule with an aromaticity comparable with those of thiazole and pyrazole, and higher than those of isoxazole and oxazole,122 140 as evaluated on the basis of Bird s aromaticity index A, based upon the statistical degree of uniformity of the bond orders of the ring periphery. Theoretical calculations and experimental data in connection with the aromaticity of isothiazole have been reviewed.141 Thiazole is also viewed as an aromatic molecule, similar to thiophene. It lacks an experimental aromaticity value, but the heat of formation together with bond lengths and angles have been calculated by various computational meth-... 

The cydoaddition of different 1,3-dipoles such as azides [331, 341] and diazoalkanes [342-344] to acceptor-substituted allenes was thoroughly investigated early and has been summarized in a comprehensive review by Broggini and Zecchi [345], The primary products of the 1,3-dipolar cycloadditions often undergo subsequent fast rearrangements, for example tautomerism to yield aromatic compounds. For instance, the five-membered heterocycles 359, generated regioselectively from allenes 357 and diazoalkanes 358, isomerize to the pyrazoles 360 (Scheme 7.50) [331]. 

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. 

Aromatic azapentalenes have not been found naturally, though an imidazo[4,5-d]imidazole derivative has been implicated in the prebiotic synthesis of purines130 74 (see also Section III,A,l,d). Saturated derivatives occur fairly widely the Senecio alkaloids contain the reduced pyrrolol l,2-a]pyrrole (pyrrolizidine) skeleton,487 and the alkaloid withasomnine is a derivative of pyrrolo[ l,2-6]pyrazole.374,488 The mitomycin antibiotics mentioned earlier in this review (Sections III,B,l,f and III,B,5) contain the pyrrolol l,2-a]indole ring,166,331 and the recently reported fungal metabolite sporidesmin is a saturated derivative of pyrrolo[2,3-6]indole.489... 

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). 

Section 2.1 is devoted to the aromatic pyrazole 1-oxides. Further structures derived from pyrazole and embedding an N-O bond are the nonaromatic 1,2-dioxides also called diazapentalene 4,4 -dioxides 75-78, the pyrazoline 1-oxides also called diazapentalene 4-oxides 79-84, and the 2-substituted pyrazoline 1-oxides represented in Scheme 22 by the parent structure 85. Structures 77, 78, 79, 81, and 82 are known and are discussed in Section 2.2 but since the present review deals with aromatic /V-oxides the nonaromatic N-oxides will only be discussed when their chemistry relates them to the aromatic pyrazole N-oxides. 

In addition to the aromatic 2-substituted pyrazole 1-oxides 74, a series of nonaromatic diazapentalene 4,4 -dioxides 75-78 and diazapental-ene 4-oxides 79-84 (Scheme 22) have been described and reviewed (1989H1615). The properties and chemistry of these compounds are related to those of the 2-substituted pyrazole 1-oxides 74. Reactions that connect the aromatic and nonaromatic pyrazole derived N-oxides have been described in Section 2.I.9.I. 

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. 

Topics reviewed during the year include the photochemistry of indoles, sulfoxides, pyrazoles and isothiazoles, (S-hetero)cyclic unsaturated carbonyl compounds, photoinduced single electron transfer (SET) reactions of amines and of azo compounds, SET reactions of organosilanes and organostannanes with Qo and ketones, photochromic polypeptides and di(hetero)arylethenes, processes in chromophore sequences on a-helical polypeptides,aryl-aryl coupling in furans, thiophenes and pyrroles," [3+2]cycloaddition of aromatic nitriles (and esters) with alkenes, and reactions of benzylsilane derivatives. ... 

---