1.5- Dicarbonyl compounds from hydrazones

In addition to preparation of arylhydrazones from the carbonyl compounds and an arylhydrazine, the Japp-Klingemann reaction of arenediazonium ions with enolates and enamines is an important method for preparation of arylhydrazones. This method provides a route to monoarylhydrazones of a-dicarbonyl compounds from /3-keto acids and to the hydrazones of pyruvate esters from / -keto esters. Enamines also give rise to monoarylhydrazones of a-diketones. Indolization of these arylhydrazones provides the expected 2-acyI-or 2-alkoxycarbonyl-indoles (equations 95-97). 

Several 3-(2H)pyridazinones have been prepared from monophenyl hydrazones of 1,2-dicarbonyl compounds and a variety of active methylene compounds within 1-20 min without solvent under focused irradiation in the presence of carefully adjusted amounts of piperidine or solid potassium tert-butoxide (isolated yields 50-89%), in accordance with Scheme 8.49 [72, 73]. 

The reaction with optically active hydrazones provided an access to optically active ketones. The butylzinc aza-enolate generated from the hydrazone 449 (derived from 4-heptanone and (,S )-1 -amino-2-(methoxymethyl)pyrrolidine (SAMP)) reacted with the cyclopropenone ketal 78 and led to 450 after hydrolysis. The reaction proceeded with 100% of 1,2-diastereoselectivity at the newly formed carbon—carbon bond (mutual diastereo-selection) and 78% of substrate-induced diastereoselectivity (with respect to the chiral induction from the SAMP hydrazone). The latter level of diastereoselection was improved to 87% by the use of the ZnCl enolate derived from 449, at the expense of a slight decrease in yield. Finally, the resulting cyclopropanone ketal 450 could be transformed to the polyfunctional open-chain dicarbonyl compound 451 by removal of the hydrazone moiety and oxymercuration of the three-membered ring (equation 192). 

Michael-type condensation of cyanoacetohydrazide (NCCH2CONHNH2, CAH) with 1,3-dicarbonyl compounds gave pyrazolo[3,4-b]pyridines under certain conditions. With l,l,l-trifluoropentane-2,4-dione in the presence of piperidine a 1 3 mixture of pyrazolone 92a and the expected aminopyridone 91a was obtained.15 The bicycle was also obtained from hydrazone (90) or by thermal reaction between its two precursors.32 Reaction of CAH and / -keto aldehydes gave good yields of only bicyclic products 92b,20 whereas ethyl benzoylacetate in the presence of piperidine gave bicycle 92c (Ar = Ph)... 

Two alternative routes lead to 2-alkyltriazole 1-oxides from a-dicarbonyl compounds (Scheme 50, routes A and B). Unsymmetrical dicarbonyl compounds frequently, but not invariably, give rise to two isomeric hydrazones and two isomeric oximes and hence two isomeric 1,2,3-triazole 1-oxides (81JCS(P1)503). 2-Phenyltriazole 1-oxide is obtained from glyoxal via route A. However, 2-methyl-triazole 1-oxide is prepared from glyoxal by route B in a one-pot process under neutral conditions. 2-Benzyltriazole 1-oxide is obtained similarly. 2,5-Dimethyltriazole 1-oxides are accessible through both routes (86ACS(B)262). 

In addition to formation from a ketone, the hydrazones can be obtained from dicarbonyl compounds by a Japp-Klingemann reaction. This is especially useful for P-ketoesters and P-ketoacids, which undergo either deacylation or decarboxylation. 

The 2-hydroxyiminohydrazones 345 are accessible from 1,2-dicarbonyl compounds via stepwise hydrazone and oxime formation, from carbonyl... 

When reviewed in CHEC-I some examples of cyclization y to the heteroatom had been described for the synthesis of pyridazines, but the method was of most importance in the synthesis of cinnolines. Examples of pyridazine syntheses included cyclization of ketazines with EDA, and intramolecular Wittig reactions of phosphoranes derived from phosphacumuleneneylides and the hydrazones produced from 1,3-dicarbonyl compounds and aryldiazonium salts. Synthetically useful approaches to cinnolines given include the intramolecular Friedel-Crafts acylation of the diacid chlorides derived from the condensation products of aryldiazonium salts and diethyl malonate to give 4(l//)-cinnolinones, and thermal cyclization of iminium hydrazones obtained from enamine esters and aryldiazonium salts. 

Mono(/ -toluenesulfonyl)hydrazones formed from a-dicarbonyl compounds and / -toluenesulfonohydrazide split off the toluenesulfonyl group when treated with alkali or, in some cases, spontaneously, and thus yield a-diazo carbonyl compounds.9 33,934... 

The initial products are the often isolable hydrazones 19, which undergo cyclization via the hemiaminal 20. Mixtures of isomeric triazines usually result from unsymmetrical 1,2-dicarbonyl compounds 3,5-disubstituted triazines 21 are predominantly obtained from 1,2-ketoaldehydes because of their different carbonyl reactivity ... 

Several 3-(2H)-pyridazinones have been prepared from monophenyl hydrazones of 1,2-dicarbonyl compounds and a variety of active methylene compounds within 1-20 min without solvent under focused irradiation conditions in the presence of carefully adjusted amounts of piperidine or solid potassium tert-butoxide (isolated yields 50-89%), in accordance with Scheme 10.109 [216]. In the synthesis of the pyridazinone 44, microwave irradiation has no specific effect, because the result (72%) was identical with that obtained by use of classical heating under the same conditions. With the dry media procedure it was possible to isolate the intermediate alkene, which was not obtained in the previously reported procedure. When the active methylene compound is a keto ester, the reaction follows a different pathway [216b]. 

The hydrazones 22 derived from partially protected o-ribose or o-glucose exist in equilibrium with the corresponding cyclic structures (Fig. 4). Subsequent cyclization of the respective hydrazine residue with 1,3-dicarbonyl compounds or unsaturated nitriles gave the pyrazoles 23 and 24 [51-55]. To-sylation of the isopropylidene derivative 23 gave the pyrazolium tosylate 26 via the intramolecular cyclization of 25 [54]. 

Primary products are the (often isolable) hydrazones 19, which cyclize to 18 via the hemiaminal 20. Mixtures of isomeric triazines are usually obtained from unsym-metrical 1,2-dicarbonyl compounds 1,2-ketoaldehydes, however, lead predominantly to... 

Formation of pyridazine ring by reaction of 1,4-dicarbonyl compounds of the type 987 was reported first in 1960, when characterization of 5,5,5-trifluorolevulinic acid (991) and its lactone 992 was performed (Scheme 211) [602]. Upon their reaction with 2,4-dinitrophenyl hydrazine (2,4-DNPG) in ethanol, a product 993 was obtained instead of 2,4-dinitrophenyl hydrazones. The starting compound 991 was obtained by hydrolysis of a Claisen adduct 990, prepared from ethyl trifluoro-acetate and diethyl succinate 989. 

Dimethylaminonitroethylene is prepared from the anion of nitromethane and the salt prepaffed from dimethylformamide and dimethyl sulfate. The condensation step is general for other types of active methylene compounds, indicating further potential for pyrrole synthesis. A related process involves the condensation of ketones with the moao-N,N-dimethylhydrazone of glyoxal base-catalyzed condensation affords the hydrazones of a conjugated 1,4-dicarbonyl system, and sodium thiosulfate reduction then affords 2,3-disubstituted pyrroles (equation 85) (77CB491). 

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