Pyrazolines pyrazolidines

MII R. Fusco, Pyrazoles, Pyrazolines, Pyrazolidines, Imidazoles, and Con-... 

R. H. Wiley (ed.), Chemistry of Heterocyclic Compounds. Vol. XXII Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles, and Condensed Rings. Wiley (Interscience), New York, 1967. 

Wiley RH, BehrLC, Fusco T, Jarboe CH (eds) (2008) Chemistry of pyrazole compounds. In Chemistry of heterocyclic Compounds pyrazoles, pyrazolines, pyrazolidines, indazoles and condensed rings. Wiley, New York... 

Behr L.C., in Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings, ed. 

R. Fusco, Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings in A. Weissberger, The Chemistry of Heterocyclic Compounds, Interscience Publ. Wiley Sons, New York London Sydney 1967. 

Tautomerism and Isomerism Syntheses of the Pyrazole Ring General Reactions of Pyrazole Compounds Chemistry of Pyrazole Compounds Introduction [to Reduced Pyrazoles] Pyrazoline Syntheses Chemistry of the Pyrazolines Pyrazolidine Chemistry... 

Neither pyrazolidines (9), which have no double bonds, nor pyrazoline diones (10), with two double bonds, and pyrazoUdine triones (11), which have three double bonds, are covered in this article. 

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

Cationic rings are readily reduced by complex hydrides under relatively mild conditions. Thus isoxazolium salts with sodium borohydride give the 2,5-dihydro derivatives (217) in ethanol, but yield the 2,3-dihydro compound (218) in MeCN/H20 (74CPB70). Pyrazolyl anions are reduced by borohydride to pyrazolines and pyrazolidines. Thiazolyl ions are reduced to 1,2-dihydrothiazoles by lithium aluminum hydride and to tetrahydrothiazoles by sodium borohydride. The tetrahydro compound is probably formed via (219), which results from proton addition to the dihydro derivative (220) containing an enamine function. 1,3-Dithiolylium salts easily add hydride ion from sodium borohydride (Scheme 20) (80AHC(27)151). 

Three double bonds. The most fully oxidized pyrazoles, the typical non-aromatic representatives of which are the pyrazoline-4,5-diones (1) and the pyrazolidine-3,4,5-triones (2), should be included here. 

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. 

Following the classification of Chapter 4.01, three classes will be considered, (a) Compounds isomeric with aromatic compounds (6), (7) and (8). The quaternary, non-aromatic salts (Scheme 7, Chapter 4.01) will be discussed only in connection with protonation studies which lead to the conclusion of their non-existence. The carbonyl derivatives (9), (10), (13) and (14) will also be included here because it is possible to write an aromatic tautomer for each one, (9 )-(14 ), even if it is energetically unfavoured, (b) Dihydro compounds. In this class not only pyrazolines (15), (16) and (17) but also pyrazolidinones (18) and pyrazolinediones like (1) are included, (c) Tetrahydro compounds. Besides the pyrazolidines (19), the pyrazolidinetriones (2) are included here. 

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. 

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. 

Pyrazolidines are cyclic hydrazones and their reactivities are comparable, the main difference being found in the oxidation of pyrazolidines to pyrazolines and pyrazoles. 

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). 

Azomethines add with great ease and stereospecificity to carbon-carbon double bonds affording pyrazolidines. They also add to carbon-carbon triple bonds with the formation of pyrazolines. Benzimidazolium iV-imines, e.g. (622), are a special case of azomethines. Its reaction with DMAD yields l-(2-methylaminophenyl)pyrazole (624), which is formed by cleavage of the initial adduct (623) (75JHC225). 

Monosubstituted hydrazones react with alkenes and alkynic compounds to yield pyrazolidines and pyrazolines, respectively (71LA(743)50, 79JOC218). Oxidation often occurs during the reaction and pyrazoles are isolated as the end product. 

The addition of a phenylcerium reagent 0 PhCeCl, ) in tctrahydrofuran to the pyrazoline 4 at — 78 C using an equimolar ratio of cerium(III) chloride, phenyllithium and pyrazoline (CcCI3/ Cf,H,I-i/4 1 1 1) exclusively provides the desired pyrazolidine 5 in good yields (75-94%). This product can be converted to the diamine 3a (R = H) and subsequently into numerous N-sub-stituted derivatives of 3a (e.g.. 3b R = CH3) by means of simple standard procedures23. 

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