A -acylpyrazoles

A-Acylpyrazoles are even weaker bases than the parent pyrazoles they form picrates and perchlorates,217,218,720 but do not dissolve in dilute acids. As mentioned above, the 1-acyl groups are quite labile. Transacylation by aminolysis is readily accomplished by treating various A-acylpyrazoles with strong amines.683, 96,728... 

The ideas for delocalization of nitrogen lone pair electron density into an aromatic or heteroaromatic system were pursued through reduction of acylated pyrazoles and imidazoles to aldehydes in high yield. 3,5-Dimethyl-A -acylpyrazoles are easy to prepare and afford 77-96% yields of aldehydes with LiAlH4 in diethyl ether at 0 Further examples of this reaction have appeared.Although these later publications commented unfavorably on the ability of LiAlH4 to reduce acyl imidazoles to aldehydes (low yields), other workers have demonstrated that yields of 60-80% could be attained at temperatures of -20 to 4-20 °C in diethyl ether.It was considered that the earlier failure may have been caused by the presence of impurities in the acyl imidazoles. The latter are easy to prepare from the parent carboxylic acid and A jV -carbonyldiimidazole. 

Ketone syntheses. Acyl derivatives that favor the arrestment of Grignard reactions beyond the first round include A-acylpyrazoles, acyl hemiacetals, and acyl tributylphosphonium chlorides (generated in situ from RCOCl and Bu,P). The protocol involving Al-methoxy-Al-methyl carboxamides has been extended to the preparation of a-chloro ketones, a-keto amides, and a-diketones (the last two from the oxalyl diamides). Symmetrical diketones are obtained by the Grignard reaction of bis(benzimidazole) methiodides. Note that an analogous reaction of 1,3-disubstituted benzimidazolium salts furnishes aldehydes. ... 

Cinchona-alkaloid-catalysed conjugate cyanation of enones has enabled the synthesis of trifluoromethyl-substituted diarylpyrroles with ee<96%P° Thiochro-manes have been formed by asymmetric domino sulfa-Michael-aldol reactions of 2-mercaptobenzaldehyde with a,/ -unsaturated A-acylpyrazoles. Asymmetric organocatalysed oxy-Michael addition to y-hydroxy a,/ -unsaturated thioesters on reaction with t-BuCHO has been used to form -hydroxy carbonyl compounds HOCH2C H(OH)CH2CO.SAr via cyclic hemiacetal intermediates. 

Since fV-acylpyrazoles have been fully described in (B-76MI40402) only a summary and some new references will be discussed here. Only neutral pyrazolides have been described, but a cationic intermediate (249) is involved in the Olofson and Kendall method of obtaining minor fV-alkylated isomers (70JOC2246). 

It should be noted that the structures assigned by von Auwers to these acylpyrazoles are not strictly proved. His attempts to confirm structure by a comparison of molecular refractions156 are scarcely conclusive, as often the exaltations of a pair of isomers are practically the same.153 The isomerism of acyl derivatives was considered in detail by von Auwers,83,86,156,281 but the data often seem quite contradictory. 

When lithium aluminum hydride reacts with N-acylpyrazoles, the CN bond is hydrogenolyzed and aldehydes are produced in good yield. Ried even recommends this as a method of preparing otherwise inaccessible aldehydes.730,781 Certain labile a-amino aldehydes were... 

A review on the synthetic utility of V-acylpyrazoles has been published <03H(60)437>. 

The pyrazole ring is resistant to most reducing agents and survives intact when other heterocycles are cleaved. An illustration is provided by the reaction of the pyrazoloimidazolidinone (1) with LAH. Here the imidazolidine unit is sensitized to nucleophilic attack by the presence of a lactam carbonyl group, and the product formed is the monocyclic pyrazole (2). The stability of pyrazoles to reduction has been exploited in a synthesis of aldehydes from acyl halides. Thus N-acylpyrazoles (3) on reduction with LAH produce complexes of the type (4) these when hydrolyzed yield aldehydes and the parent pyrazoles (5). ... 

Allyl ketones. Reaction of acid chlorides or 1-acylpyrazoles with allylindium bromide in water is a convenient method for synthesis of allyl ketones. The divergent... 

There are several reports on condensation reactions of 4-acylpyrazol-3-ones with primary amines (70LA75, 81AJC1117, 90M1023, 98JMC4001, 00JCR(M)622, 02IJC(A)554, 03JHC963), two of which describe reactions with thiourea and... 

An indirect way of introducing a substituted aminohydroxypropyl group at position 1 of l,2-dihydropyrazol-3-ones was devised by Holzer, Ecker and co-workers (98JMC4001) (Scheme 8). The method consists of reacting the sodium salt of 4-acylpyrazol-3-ones 23a-l with excess epichlorohydrin and successively... 

Dieckmann and Claisen condensations. Dieckmann cyclization and Claisen condensation of M-acylpyrazoles are catalyzed by MgBr -RjN. Note that a practical >ynthesis of a-acylamino-P-ketoesters employs MgClj-EtjN to induce the reaction between alkyl hydrogen (acylamino)malonates and acyl chlorides. ... 

Inspired by their previous work dealing with enantioselective conjugate addition of t-butyl acetoacetate to crotonoylthiazolidinethione catalysed by a preformed nickel catalyst from/>-To 1-BINAP ligand 30, and by those of Kane-masa on enantioselective nickel-catalysed additions of thiols and 1,3-dike-tones to unsaturated acylpyrazoles and oxazolidinones with a chiral amine ligand, Evans et al. investigated the scope of enantioselective Michael... 

N-Condensed N-acylpyrazole ring from cyclic a-diazoketones Ring expansion with ring closure... 

Aldehydes from carboxylic and chlorides yia a-diazoketones and 1-acylpyrazoles Synthesis with addition of 1 C-atom... 

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