Reactions of Vanillin and Vanillal Esters with 6-Quinolylamine and Phenidone

Abstract

Previously unknown 2-methoxy(or ethoxy)-4- (11-oxo-9-phenyl-7,8,9,10,11,12-hexahydrobenzo-[b] [4,7]phenanthrolin-12-yl)phenyl esters of carboxylic acids were prepared by ternary condensation of vanillin or vanillal alkanoates with 6-quinolylamine and Phenidone. According to the 1 H NMR spectra, the target products are formed as mixtures of diastereomers.Vanillin and vanillal (4-hydroxy-3-metoxy-and 4-hydroxy-3-ethoxybenzaldehyde), which are plant phenols, are widely used as fragrant additives in food industry, perfumery, and cosmetics, and also as versatile reagents in organic synthesis [1,2]. In particular, vanillin and vanillal can be modified by esterification of the hydroxy group with chlorides or anhydrides of organic acids of various classes. The resulting vanillin and vanillal derivatives contain both ether and ester groups. Reactions of such compounds with arylamines and CH acids open prospects for preparing biologically active condensed nitrogen-containing heterocycles with alkoxy and alkylcarboxy fragments [3,4]; these fragments increase the solubility of the compounds in aqueous alcohol and extend the possibilities of biological testing and application.We showed in [4] that vanillin alkanoates react with 6-quinolylamine and 1,3-cyclohexanedione to form 2-methoxy-4- (11-oxo-7,8,9,10,11,12-hexahydrobenzo[b][4,7]phenanthrolin-12-yl)phenyl esters of carboxylic acids; with dimedone taken instead of 1,3-cyclohexanedione, the corresponding 9,9-dimethyl derivatives are formed.In this study, with the aim to prepare new compounds of this class, we performed condensation of vanillin and vanillal alkanoates Ia3Ic and IIa3IIc with 6-quinolylamine III and 5-phenylcyclohexane-1,3-dione (Phenidone) IV.Esters Ia3Ic and IIa3IIc were prepared in 80 390% yields from the corresponding acid chlorides and vanillin or vanillal, by refluxing in CH 2 Cl 2 in the presence of pyridine.The condensation of Ia3Ic and IIa3IIc with III and IV was performed by refluxing the equimolar amounts of the reactants in 1-butanol without catalyst.The desired 2-methoxy(or ethoxy)-4-(11-oxo-9-phenyl-7, 8,9,10,11,12-hexahydrobenzo[b][4,7]phenanthrolin-12-yl)phenyl esters of carboxylic acids Va3Vc and VIa3VIc were thus prepared in 58370% yields. The compounds, according to the NMR spectra, are approximately equimolar mixtures of two diastereomers differing in the position of the phenyl group at C 9 (pseudoaxial or pseudoequatorial).The target products Va3Vc and VIa3VIc can form by different pathways depending on the order in which the components react with each other. Among possible intermediates A3D, the key species is amino keto enol C undergoing cyclocondensation to phenoxycarbonyl-substituted benzo[b] [4,7]phenanthroline. Amino keto enol C can form either by addition of the intermediate arylmethylenephenidone A to 6-quinolylamine at the 5-C atom of the quinolyl ring, bearing the highest electron density [5], or by rearrangement of amino hydroxy ketone D following the pattern of the Hofmann3Martius rearrangement [6]. In turn, intermediate D is f...

Reactivity and stability of selected flavor compounds

“…If its hydroxyl group is protected, vanillin can be oxidized to generate vanillic acid. Phenol is converted to esters and ethers, while the nucleus is readily substituted by halogen and nitro groups [ 59 , 64 , 65 ]. Oxidation of vanillin can occur both under alkaline condition and by enzymes including milk enzymes such as xanthine oxidase and peroxidase.…”

Newly Designed and Synthesized Curcumin Analogs with in vitro Cytotoxicity and Tubulin Polymerization Activity

“…Analogs IVa-d, VIa and VIIa,b, IXa and Xa-c, and XIIae which represent four different series of compounds were designed and synthesized with 1,5-diaryl-3-oxo-1,4-pentadienyl core moiety. Reported intermediates IIa-d of series 1, Va,b of series 2, and XIa,c,d of series 4 were prepared according to reported procedures (18)(19)(20)(21)(22)(23)(24)(25). The syntheses of the target compounds IVa-d of series 1 follow two-step procedure.…”