Acetylmalonic acid

Acetylmalonic Acid, CH3 CO CH (COOH) 2, and Acetone-dicarboxylic Acid, CO (CH2COOH) 2, do not permit their anions to unite (Weems2). 

The cyclocondensation of 2-acetylmalonic acid diethyl ester 41 with hydrazine hydrate 42 gave pyrazol-3-one 44, after tautomerism of the initially formed intermediate 43 (05H77) (Scheme 10). 

Diethyl acetylmalonate was reacted with anilines in benzene in the presence of a catalytic amount of concentrated hydrochloric acid at 65-70°C for 16 hr. Then, after evaporation, the residues were heated at 195-220°C for 5-15 min to give 2-methylquinoline-3-carboxylates (666) in 36-80% yields (83KGS 1521). Meta-substituted anilines (R = Me, Cl) gave 7-substituted 2-methylquinoline-3-carboxylates. 

Sardesai and Sunthankar studied the cyclization of diethyl )V-(2-amino-phenyl)aminomethylenemalonate (162, R = H) (57MI2 59MI1). No cyclization occurred in refluxing xylene in the presence or absence of a catalyst (p-toluenesulfonic acid or sodium hydroxide), or in acetic anhydride, or in a mixture of acetic anhydride and concentrated sulfuric acid. Benzimidazole and benzimidazolone were obtained in 20% and 66% yields, respectively, when 162 (R = H) was distilled in vacuo. Benzimidazolone was the product when 162 (R = H) was heated in boiling diphenyl ether, o-Phenylenediamine was reacted with diethyl acetylmalonate at 140°C for 4 hr to give 2-methylbenzimidazole and diethyl malonate (85S555). 

In the cyclocondensation of diethyl acetylmalonate and 4-alkylamino-1,5-benzodiazepines (1411) in benzene in the presence of acetic acid and piperidine, the addition of acetylmalonate at the side-chain double bond of 1411 took place first. The amino group at position 4 was involved only in the second step of the reaction sequence to give tricyclic derivatives (1412) in 49-77% yields (85FES391). 

Ethyl 3-methyl-5-oxopyrazoline-4-carboxylate and its I-methyl derivative were prepared in the reaction of diethyl acetylmalonate and hydrazine hydrate, and methylhydrazine in acetic acid at 95-100°C for 3 hr in 83% and 95% yields, respectively (89SC2087). 

On the other hand, 3-ketoesters with unsubstituted AT nearly exclusively lead to normal 7-oxo-derivatives (71CB2702) as given in Scheme 1. An exception is the formation of 5-oxo-6-carbethoxy-7-methyl-TP from diethyl acetylmalonate (66UP1) in acetic acid, DMF, or DMSO (with poor yield only). 

Depending upon the reaction conditions, 2-ethoxy-3,4,5,6-tetrahydropy-ridine and isopropylidene 2-acetylmalonate afforded either perhydropy-rido[2,l-h][l,3]oxazine-2,4-dione (162) or hexahydropyrido[2,l-b][l,3]ox-azine-3-carboxylic acid (163) (86MI1). Reaction of 2-methoxy-3,4,5, 6-tetrahydropyridine with diketene without a solvent gave a mixture of 4H-quinazolin-4-one (164) and hexahydropyrido[2,l-h][l,3]oxazin-4-one (165) [75H(3)927]. 

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