Pyrazolidines reduction

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 yield is variable depending on the degree of dryness ol CeCf, and the hydroxide contcm of thcC n5Li. b The N-N bond of 5 cannot be cleaved under the usual reaction conditions. Only when the pyrazolidine is deprotected. can the reduction be accomplished. c The yield is variable depending on the reaction scale. 

Pyrazolopyrazoloquinoline derivatives can be prepared by treatment of pyrazolidin-3-one with 2-chloroquinoline-3-carbaldehyde, which gives firstly the zwitterionic compound 283. Reduction with sodium borohydride followed by ring closure in basic media gives the fused tricyclic heterocycles (Scheme 77) <1991T9599>. 

Esters of racemic pyrazolidine-3-carboxylic acid (5-azaproline, 16) are obtained by a two-step reaction via addition of diazomethane to acrylic acid esters to form the corresponding dihydropyrazoline derivatives, which are converted into the desired pyrazolidine-3-carb-oxylic acid derivative by hydrogenation over palladium on charcoal,11621 or by reduction with sodium cyanoborohydride,[164l or with zinc in acetic acid. Details are given in Table 6J1651... 

A practicable strategy to provide access to chiral pyrazolidine-3-carboxylic acid (16) makes use of asymmetric dipolar cycloaddition of diazoalkanes to u,p-unsaturated carboxylic acid derivatives. For this purpose a chiral auxiliary of the alkene component is used, e.g. Op-polzer s1166 1671 (lf )-2,10-camphorsultam.t164l As shown in Scheme 7, by reaction of (tri-methylsilyl)diazomethane (41) with /V-( aery I oy I )cam p h ors u 11 am (42), the AL(4,5-dihy-dropyrazoline-5-carbonyl)camphorsultam (43) is obtained. Reduction of 44 with sodium cyanoborohydride leads to A-(pyrazolidine-3-carbonyl)camphorsultam (45) as the 35-dia-stereoisomer (ee 9 1) in 65 to 80% yields.[164] The camphorsultam 45 is then converted into the methyl ester 46 by reaction with magnesium methylate without racemizationj1641... 

A reductive ring closure of a (8-dioxime (72) to a pyrazolidine (73) was reported00 to occur in 30% sulfuric acid at a lead cathode. The following mechanism (Scheme 7) may operate in which the loss of water from the intermediate hydroxylamine may be assisted by the acid.89... 

Enantioselective [3+2] cycloaddition of halohydrazones 692 with dipolarophile 691 in the presence of ligand 693 under Lewis acid conditions, followed by reduction, provided an entry to chiral dihydropyrazole scaffolds 694 in excellent yields and good ees (Scheme 86) <2005JA8276>. Highly enantioselective synthesis of pyrazolidines 698 was achieved by the [3+2] acylhydrazone-enol ether cycloadditions of 695 and 696 in the presence of a chiral silicon Lewis acid 697 (Equation 148) <2005JA9974>. 

The LAH reduction of alkyl- and arylpyrazolium salts (246) has been investigated and leads to a mixture of the 3- (247) and 4-pyrazolines (248), along with the fully saturated pyrazolidine 249 in some cases. The exact... 

One of the more frequently reported routes to 1,5-diazocines involves reductive nitrogen-nitrogen bond cleavage of N.A -trimethylenepyrazoli-dines (56) to yield 57. This reaction was first reported by Wiselogle and co-workers, who reacted 2 mol of trimethylene bromide or chloride with 1 mol of hydrazine. They obtained, in addition to 56 (R = R1 = H) and pyrazolidine, the corresponding ring-opened compound 57 (R = R1 = H)... 

The reduction of A -pyrazolines into pyrazolidines will be examined with these last compounds (see Section 3.01.6.3). There, the Grignard reaction will be used to transform pyrazolines (171) and... 

Pyrazole resistant to oxidation and reduction reaction due to loss of aromaticity, but may be hydrogenated catalytically, first to pyrazoline, and then to pyrazolidine. Both of these compounds are stronger bases than p3rrazole. 

Pyrazolidine Derivatives. The reduction of some aminopyrazole quaternary salts (301) with sodium borohydride or lithium aluminium hydride leads to pyrazolidinone derivatives, e.g. (302), and ring-opened products. ... 

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