The Reaction of Acetals with Malonic Acid and its Derivatives. A Contribution to the Knowledge of the Knoevenagel-Doebner Reaction

Abstract

The acetals of aromatic aldehydes, cinnamic aldehydes and-with lower yields-also of aliphatic aldehydes react withThe reaction does not Ethyl hydrogen malonate reacts with these acetals analogously in the absence of any catal>Tst, -4 reaction mechanism is proposed, inmalonic acid in the presence of pyridine and piperidine in the manner of a Knoevenagel reaction. proceed via the free aldehydes.giving the corresponding ethyl hydrogen arylidene-and cinnamylidene-malonates. voking the formation of a hydrogen-bonded complex between the two components of the reaction mixture.In a study to be published elsewhere, it was found that the acetals of 2-phenyl-1,2,3,6-tetrahydro-and 2-phenyl-hexahydrobenzaldehyde react with malonic acid in the presence of pyridine and piperidine in the manner of a Knoevenagel reaction, giving the corresponding hydrogenated 2-phenylcinnamic acids, with liberation of carbon dioxide. A systematic study of the reaction between dialkyl acetals of aldehydes and malonic acid led to the following conclusions : the diethylacetals of aromatic and of cinnamic aldehydes condense with malonic acid in quantitative yields. The aromatic aldehyde acetals thus give cinnamic acids. This is particularly noteworthy in the case of p-diinethylaminobenzaldehyde diethylacetal ; this aldehyde is refractory in the Perkin reaction' but gives2 by Doebner's method a yield of 85Y0. Bulky o-substituents (not, e.g., o-methoxy) decrease the yield under the same operating conditions (to 50-607,) ; prolongation of the reaction time gives satisfactory yields also in these cases. It appears that these substituents decrease the rate a t which condensation takes place. The acetals of aliphatic and hydroaromatic aldehydes react more slowly than those of aromatic ones, giving a,&unsaturated monocarboxylic acids. The yields were low, but at least in a number of these cases the acetals have been recovered, so that not the yield but rather the conversion rates appear to be affected adversely.The reaction between the acetals of cinnamic aldehydes and malonic acid leads to mixtures of the corresponding malonic and monocarboxylic acids ; i t has been shown that the former are decarboxylated only slowly, even in boiling ~y r i d i n e .~ Thus it must be assumed that the proximity of the aryl groups accelerates the decarboxylation. This assumption is supported by the observation that ethyl hydrogen (p-methylbenzy1idene)-malonate

Synthesis of new functionalized aryl‐substituted methylphosphonic and methylenediphosphonic acids and their derivatives

“…Easily available aromatic aldehydes diethyl acetals react with trimethylsilyl phosphites similarly but only under heating at 100‐150°C to give ethoxymethylphosphonates 3 in high yields. The synthesis of the phosphonate 3b proceeds only in the presence of a mixture of zinc chloride and cadmium iodide as catalysts.…”

“…All reactions were carried out under dry argon in anhydrous solvents. The starting trimethylsilyl esters of trivalent phosphorus acids, aldehyde acetales, and substituted benzalchlorides were prepared as described below.…”

The synthesis of 3-carboxymethyleneazetidinones

“…The dimethyl acetal 6 (5,6) and the protected cyanohydrin derivatives 8 and 9 (7-9) were readily prepared following standard '~uthor to whom correspondence may be addressed.…”

Reactions of Ortho Esters Which Result in Carbon-Oxygen and Carbon-Halogen Bond Formation

“…Since many acetals and ketals are extremely susceptible to acid-catalyzed hydrolysis and dealcoholysis, the final work-up should be carried out under alkaline conditions, with the exclusion of moisture. A number of good general procedures for converting aldehydes and ketones to acetals and ketals by reaction with orthoformates and alcohols have been described in the literature (6,23,67,151,160,248,285).…”

“…C 3 compounds: propionaldehyde (225), 2,2-dibromopropanal (67, 127, 151a, 187, 250, 255, 290), 2-fluoro-5-hydroxypropanal (156), acetone (9,11,59,64,67,69,107,137,143,190,220,223), chloroacetone (9), acetoxyacetone (102) 1,1-dichloroacetone (301), l-acetoxy-3-hydroxyacetone (8, 23a, 110), acrolein (111,231,247,285) (64,67,126,279), 5-ethoxyfurfural (109), 3methylthio-2-thiophenecarboxaldehyde (124b), and 2-selenophenecarboxaldehyde (217). C 6 compounds: 2-hexanone (11,101), 3,3-dimethyl-2-butanone (16,59,220), 6-formyloxyhexanal (4, 5), 2-methylcyclopentanone (5), cyclohexanone (12,151,178,190,215,248), 2-methyl-l-penten-3-one (8) (64,67,108,160,225), m-aminobenzaldehyde (42), m-and /?-nitrobenzaldehyde (108), /?-chlorobenzaldehyde (108), ο-, m-, and /7-hydroxybenzaldehyde (34,…”