The Acetoacetic Ester Synthesis: Synthesis of Methyl Ketones ..

Malonic ester synthesis of carboxylic acids: Acetoacetic ester synthesis of methyl ketones 1.
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Acetoacetic Ester Synthesis - University of Calgary

This problem can be overcome by employing -methoxy--methyl amides (see ) as acylating agents. Addition of catalytic amounts of greatly improves the efficiency of acylation of dilithio ethyl acetoacetate (eq 10). -Dimethyl carboxamides can also be used as acylating agents in the presence of .Knoevenagel condensation of acetoacetates with carbonyl compounds may be carried out using a wide range of catalysts and reaction conditions. A particularly mild and efficient procedure involves the use of and pyridine in THF at low temperatures, which allows the condensation of ethyl acetoacetate with aliphatic, aromatic, and heteroaromatic aldehydes to produce -alkylideneacetoacetates (eq 11). The condensation of -butyl acetoacetate with aldehydes and subsequent cleavage of the -butyl ester by heating with catalytic provides a convenient synthesis of ,-unsaturated methyl ketones. -Alkyl-substituted acetoacetates can add to aldehydes; however, the adducts often undergo acyl cleavage under the reaction conditions to give ,-unsaturated

Under the conditions of the classical acetoacetic ester route to methyl ketones [see, ..
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Claisen Condensation, Acetoacetic Ester and ..

Under the conditions of the classical acetoacetic ester route to methyl ketones [see, e.g.: Org. Synth. Coll., 1, 248, 351 (1941)], varying amounts of O-alkylation occur. Regioselective C-alkylation can be obtained by phase-transfer procedures: J. Org. Chem., 39, 3271 (1974). For improved alkylation using TBAB, see: Org. Prep. Proced. Int., 26, 469 (1994). Many techniques have been devised for the decarboalkoxylation of substituted ß-ketoesters (compare ); for reviews, see: Synthesis, 805, 893 (1982). Enolisable ß-keto esters can be decarboalkoxylated by heating in toluene in the presence of a catalytic amount of DMAP. Other bases are ineffective: J. Org. Chem., 54, 3474 (1989). For use in diazo transfer reactions, see . Xu, L.; Jiang, Y. G.; Feng, J. Z.; Feng, J. Influence of Ethyl Acetoacetate on the Structure and Thermal Stability of Alumina Aerogel. Mater. Sci. Forum 2015, 816, 157-162.Dehghan, A.; Singh, S.; Abbasinejad, M. A.; Hassanabadi, A. Four-component reaction between cyanoacetamide, aryl aldehydes, and ethyl acetoacetate with ammonium carbonate. Res. Chem. Intermed. 2015, 41 (2), 1001-1009.

57 The acetoacetic ester synthesis is useful for preparing methyl ketones.
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Alkylation at the -carbon of ethyl acetoacetate via an alkali metal enolate and subsequent removal of the ester group by sequential hydrolysis and decarboxylation provides a classical synthesis of methyl ketones (eq 1). The ambident reactivity of the acetoacetate anion often causes competing - and -alkylations. The extent of vs.

An acetoacetic ester synthesis of a ketone proceeds by alkylation of the ..
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