Reactivity centres among nucleophilic substituted arylidene acetophenone towards attack by active methylene group [Part XI] synthesis of newer carboxylic acids, cyclic hydrazides, isoxazole and pyridine derive

Hans stobbe [1] stated that alpha beta-unsaturated ketones failed to undergo the Stobbe condensation but form Michael adducts. Patwardhan [2] generalized the reactivity of the carbonyl group in the presence of potassium tert-butoxide, giving the corresponding half-esters in a low yield. Recently [3], we have reported on the reactivity of both centers with special attention to the participation in the Michael and Stobbe condensation. The results obtained in the present study are considered to be rather conclusive in establishing the role of the polar factor in the reactivity of the carbonyl carbon in chalkones. To undergo the Stobbe condensation in a good yield, there must be an electron donating substituents which favours the formation of the intermediate lactone proposed in the currently accepted mechanism[4]] Secondly there must be high concentration of ester group for consuming the protonium ion in alcohol formation. The protonium ion assumed as a by-product [5] and leading to the formation of the competing Michael addition at the expense of the Stobbe condensation. The present investigation was planned to substantiate this conclusion. Thus twelve chalkones having substituents of different polar nature were condensed with succinic ester in the presence of potassium tert-butoxide and the composition of the reaction products were determined. The results obtained may be considered as a contribution characterized to the work done by Hans Stobbe and Patwardhan. An elegant support for the importance of the polar factor can be shown by the failure of the alpha, beta-unsaturated ketones having an electron attracting group to undergo the Stobbe condensation, where the maximum yield range from 3-10 percent it is interesting to note that the yields of the half-esters increase with the increase of the number of the methyl and methoxyl substituents, whereby the half-ester attains 70 percent when the tetra-substituted chalkone was utilized in the Stobbe condensation. For this purpose we reacted 4,4'- dimethoxy, 4-methoxy 3/4'-dimethyl and 2.3-dimethoxy 3', 4'-dimethyl chalkones with dimethyl succinate to verify good yields of the half-esters [see Experimental]. The IR spectra of these compounds showed absorption bands of the dimeric carboxylic groups for esters and acids. Alkaline hydrolysis of the half-esters gave the corresponding dibasic acids of the type [Ib] and [IIb]. The structure of these acids was supported by analytical data, IR spectra and the facile conversion into the corresponding cyclic hydrazide [IIIa],upon treatment with hydrazine hydrate. The IR spectrum of compound IIIa showed characteristic absorption bands at 3380, 1660, 1620 and 1600 cm[-1] The reactions with dimethyl sulphate [6] and methyl isocyanate to form dimethyl and dicarba-mate succinhydrazide derivatives, IIIb, c were considered as additional evidence for the assigned structure IIIa The reaction of chalkones and cyanoacetamide in the presence of ammonium acetate afforded cyanopyridones [IVa],[IVb] and cyanodihydropyridone [V] [7], rested upon correct analytical and spectral data. When 4-methoxy 3',4'-dimethyl chalkone was brominated in acetic acid, it afforded the dibromide which upon treatment with hydroxylamine hydro-chloride under conditions similar to those described by Nakata [8] for isoxazole synthesis, compound VI was obtained, the structure of which is supported by a study of electronic spectrum which is similar to that previously described [9]. It has been assumed [10] that the isoxazoles are obtained through the formation of acetylenic oxime presumably formed as an intermediate through dehydrobromination, followed by intramolecular cycloaddition. The reaction of 4-methoxy 3,'4'-dimethyl chalkone with ethylcyanoacetate in presence of ammonium acetate, afforded VII. Whether the reaction was carried out with or without a solvent, the same product was obtained. However, compound VII is not identical with that formed by Sakurai and Midorikawa [11] for the reaction of unsubstituted alpha, beta- unsaturated ketones with ethylcyanoacetate as shown by spectral and analytical data. The reaction of 4-methoxy 3', 4 -dimethyl chalkone with malononitrile [12] afforded cyanoaminopyridine [VIII]. The IR spectrum showed the frequency bands due to asymmetric and symmetric stretching vibrations of primary amines as multiple bands of medium intensity. The corresponding bending vibrations cause absorption in the 1630 cm[-1] region as 2-amino pyridine, in addition to the characteristic absorption bands for the cyano group

Heterocycles from dicarboxylic acids Synthesis of new lactones, succinhydrazides and pyridazine derivative XIII

The title compounds were prepared via two different routes. Thus the dicarboxylic acids [I] and [II] previously prepared by the author [1], when treated with bromine in acetic acid, lactones [IIIa, b] were formed through the elimination of hydrogen bromide [2]. The I.R. spectrum of these compounds showed the characteristic absorption bands for lactones and carboxylic acids

Reactivity centres in the dimethoxybenzylidene acetophenone towards attack by active methylene compounds [Part X]: synthesis of five membered ring compounds

While malononitrile and cyanoacetamide react with 2,3-dimethox-y benzylideneacetophenone to give pyridine and pyridone derivatives, through Michael condensation, the reaction with succinic ester condenses in the Stobbe type affording the half-ester [IIa]. This undergoes cyclization to five membered ring compounds via two different routes. The synthesis of isoxazole [IX], oxadiazole [XIa] and thiazole [Xlb] is also described. The biological activity of these compounds is evaluated and discussed

Heterocycles and oxime carbamates from arylidene indanones Reactions of indanone with aldehydes and succinic esters: Part [XIV]

It has been stated [1] that the condensation of aldehydes with indanone gave the corresponding arylidene indanone derivatives