A?-pyrazoline

Reaction of arninoacetonitrile hydrochloride with sodium nitrite provides diazoacetonittile (62). The product undergoes a 1,3-dipolar cycloaddition with diethyl fumarate to yield a pyrazoline intermediate, which without isolation reacts with ammonia in water to furnish the pyrazole [119741-54-7] (63) (eq. 14) (43). 

C3N2 N N — — — Pyrazole substituted pyrazoles A - and A -pyrazolines pyrazolinones pyrazolidines pyrazolidinones... 

A -Pyrazolines are converted into pyrazoles by oxidation with bromine or Pb(OAc)4 and... 

A -Pyrazolines and A -isoxazolines (302 Z = NH, O) are cyclic hydrazones and oximes, respectively. 2-Pyrazolines are quaternized at the 2-position (306 307) (64AHC(. ll). 1,3,4-Oxadiazolines (e.g. 308) are very easily ring-opened (66AHCi7 183). 

One double bond. The three pyrazolines, A - (15), A - (16) and A -pyrazoline (17), and the carbonyl derivatives of pyrazolidines like (18), are the most representative compounds of this group. 

Chemical shifts for some representatives of the less common class of A -pyrazolines are shown in Table 13. These cyclic enehydrazines are also probably puckered (69) however, no X-ray determination nor conformational study has been carried out to solve this problem. Compound (70) is representative of the rare N(l)-unsubstituted A -pyrazolines prepared by Burger et al. (79T389). 

The salts (71) and (72) are both A -pyrazoline derivatives. However, the first one is obtained by quaternization of a A -pyrazoline and the second one by protonation of a A -pyrazoline (Section 4.04.2.2.2(v)). Several A -pyrazolinium salts (72) and their NMR spectra are described in (69BSF3292,71T123) and for A -pyrazolinium salts (73) see (69BSF3316). 

A large amount of data on A -pyrazolines has been collected but not completely published. Some values can be found in Figure 15. 

Figure 15 C chemical shifts (p.p.m.) of A -pyrazolines and their salts...

Finally, A -pyrazolines lose N2 (73KGS64) but it is possible that this takes place thermally before ionization, since thermolysis of A -pyrazolines usually gives cyclopropanes (Section 4.04.2.2.2(iv)). 

The conformation of heteroethylenic rings. A - and A -pyrazolines, and the nitrogen inversion and preferred orientation of the IV-methyl groups in pyrazolidines (71T123) have been discussed in connection with their NMR spectra (Section 4.04.1.3.3). 

A -Pyrazolines are obtained by the reduction of pyrazoles with sodium and alcohol, by catalytic hydrogenation on palladium or by electrochemical means (B-76MI40402). In some cases the reduction proceeds further yielding pyrazolidines and open-chain compounds. 

A mechanism has been proposed to rationalize the results shown in Figure 23. The relative proportion of the A -pyrazolines obtained by the reduction of pyrazolium salts depends on steric and electronic effects. When all the substituents are alkyl groups, the hydride ion attacks the less hindered carbon atom for example when = Bu only C-5 is attacked. The smaller deuterohydride ion is less sensitive to steric effects and consequently the reaction is less selective (73BSF288). Phenyl substituents, both on the nitrogen atom and on the carbon atoms, direct the hydride attack selectively to one carbon atom and the isolated A -pyrazoline has the C—C double bond conjugated with the phenyl (328 R or R = Ph). Open-chain compounds are always formed during the reduction of pyrazolium salts, becoming predominant in the reduction of amino substituted pyrazoliums. 

Hi) Electrochemical reactions and reactions with free electrons Electrochemical oxidation of 3-methyl-l-phenylpyrazole gave the 3-carboxylic acid whereas electrochemical reduction (Section 4.04.2.1.6(i)) of l,5-diphenyl-3-styrylpyrazole produced the A -pyrazoline (B-76MI40402) with concomitant reduction of the exocyclic double bond (343). 

Further evidence showed this mechanism to be incorrect, especially the fact that it was methyl cinnamate and not (347) which was isolated from the reaction (73CPB2026). Also 1-phenylpyrazoles did not react with DMAD under the reaction conditions (74BSF2547). The origin of (346) remains obscure, but in no circumstances does it imply a Diels-Alder reaction of a pyrazole. For Ogura et al., it has its origin in an intermediate A -pyrazoline (73CPB2026). 

Isopyrazole quaternary salts (363) are key intermediates leading to the highly substituted A -pyrazolines. Lithium aluminum hydride gives the pentasubstituted derivatives (364 R = H) and Grignard reagents provide access to the fully substituted A -pyrazolines (364 R H) (68BSF3866, 70BSF1121). 

According to the classification of Section 4.04.1.1.3 this section deals with A -(IS), A -(16) and A -pyrazolines (17), and with pyrazolidones (18) and aminopyrazolines. The number of publications dealing with these compounds is so large that only the most relevant results and most important references will be described. The Jarboe review on pyrazolines (67HC(22)l) contains information up to 1963 and fortunately the chemistry of pyrazolidones and aminopyrazolines is covered by an excellent review by Dorn in 1980 (8OCHEI). 

Tautomerism has been discussed in Section 4.04.1.5.2. It concerns prototropic tautomerism and the decreasing order of stability is (hydrazone) >A (azo)> A (enehydrazine). The isomerization A -> A occurs via a A -pyrazoline (65BSF769). Pyrazolidones and amino-A -pyrazolines exist as such. The only example of non-prototropic tautomerism deals with the isomerization (403) —> (404) (74CJC3474). This intramolecular process is another example (Section 4.04.1.5) of the thermodynamic analogy between prototropy and metallotropy. 

A -Pyrazolines such as (410) are oxidized by iodine, mercury(II) acetate and trityl chloride to pyrazolium salts (411), and compound (410) even reduces silver nitrate to Ag° (69JOU1480). Electrochemical oxidation of l,3,5-triaryl-2-pyrazolines has been studied in detail (74BSF768, 79CHE115). They Undergo oxidative dimerization and subsequent transformation into the pyrazole derivative (412). 

The fundamental subject of this section is the transformation of A -pyrazolines into cyclopropanes (Buchner-Curtius and Kishner cyclopropane syntheses). The cyclopropane is often accompanied by alkenes (67HC(22)l). When applied to A -pyrazolines the reaction occurs via the A isomers (Scheme 37). 

The stereochemistry of pyrazolines and pyrazolidines has already been discussed (Section 4.04.1.4.3). Optically active A - and A -pyrazolines have seldom been described (77JA2740, 79CJC360), but cis-trans isomeric pairs are common. The C-4 acid-catalyzed epimerization involves the mechanism shown in Scheme 38 (70TL3099), but in spite of some inconclusive arguments the C-5 epimerization has never been established with certainty. 

Analogous to the oxidation of hydrazones to azo compounds, A-unsubstituted pyrazolidines are oxidized to A -pyrazolines. For example, the blcyclic pyrazolidine (415) when treated with silver oxide yields the pyrazoline (416) (65JA3023). Pyrazolidine (417) is transformed into the perchlorate of the pyrazolium salt (411) by reaction with mercury(II) acetate in ethanol followed by addition of sodium perchlorate (69JOU1480). 

The pyrazole (420) is formed when the pyrazolidine (418) is heated with chloranil and the intermediate A -pyrazoline (419) (one of the rare A(l)-unsubstituted derivatives) can be isolated (78TL4503). 

The important synthesis of pyrazoles and pyrazolines from aldazines and ketazines belongs to this subsection. Formic acid has often been used to carry out the cyclization (66AHQ6)347) and N-formyl-A -pyrazolines are obtained. The proposed mechanism (70BSF4119) involves the electrocyclic ring closure of the intermediate (587) to the pyrazoline (588 R = H) which subsequently partially isomerizes to the more stable trans isomer (589 R = H) (Section 4.04.2.2.2(vi)). Both isomers are formylated in the final step (R = CHO). 

Diazo compounds react with alkenes to afford A -pyrazolines, which in turn izomerize to A -pyrazolines if there is a hydrogen atom a to the N=N bond (Scheme 54). In those cases where two possible ways of isomerization exist, the more acidic hydrogen migrates preferentially. The alkene configuration is conserved on the A -pyrazoline (stereospecificity) but the regioselectivity depends on the substituents of both the alkene and the diazo compound. 

Burger s criss-cross cycloaddition reaction of hexafluoracetone-azine (76S349) is also a synthetic method of the [CNN + CC] class. In turn, the azomethines thus produced, (625) and (626) (79LA133), can react with alkenes and alkynes to yield azapentalene derivatives (627) and (628), or isomerize to A -pyrazolines (629) which subsequently lose HCF3 to afford pyrazoles (630 Scheme 56) (82MI40401). 

The synthesis of A -pyrazolines by reaction of a 1,2-disubstituted hydrazine, formalin and a carbonyl compound, known as the Hinman synthesis, probably proceeds by the mechanism shown in Scheme 57 (69BSF3300). 

H) has been isolated (636). With monosubstituted hydrazines and aldehydes, A -pyrazolines (637) are formed (69CHE805). 

A -pyrazolines from, 5, 250 structure, 5, 169 Isoquinoline, 4-acetamido-reduction, 2, 327... 

The addition of diazomethane to unsaturated esters (1), as ethyl acrylate, methyl crotonate and ethyl cinnamate, was investigated by Auwers who showed that the primary addition product is a A -pyrazoline (2) which rearranges spontaneously to the conjugated A -pyrazoline (3). 

However, in the case of a-substituted unsaturated esters (4), as for example methacrylic or tiglic acid esters, diazomethane addition results in the formation of stable A pyrazolines (5). The latter products require halogen acids for conversion to the isomeric nonconjugated A -pyrazolines (6). 

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