Orthoformate, reaction with diethyl malonate

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

Active Methylene Compounds. Triethyl orthoformate can formylate diethyl malonate under slightly acidic conditions. With less activated compounds it can be induced to undergo a Mannich reaction, and can also formylate a cyclohexanone enolate anion (eq 9). ... 

Snyder and Jones obtained ethyl N-(3-chlorophenyl)aminomethyl-enemalonamate (244) in 77% yield when 2 mol of 3-chloroaniline was reacted with 1 mol of diethyl malonate and 1 mol of ethyl orthoformate at 160-165°C. The ethanol formed during the reaction was distilled off (46JA1253). 

The uncatalyzed reactions between anilines, ethyl orthoformate, and diethyl malonate afforded ethyl arylaminomethylenemalonamates (252) in 67-85% yields (87SC549). However, if the malonate was first reacted with ethyl orthoformate and acetic anhydride in the presence of a catalytic amount of ZnCl2 at boiling temperature for 5 hr and aniline was then added to the reaction mixture, reflux being maintained for 0.5 hr, arylaminomethylenemalonates (253) were obtained in 52-85% yields. 

Guo et al. prepared N-(3-chloro-4-fluorophenyl)aminomethylenemalo-nate (256, R = 3-C1, R1 = 4-F, R2 = R3 = Et) in 60-70% yields when 3-chloro-4-fluoroaniline was reacted with triethyl orthoformate and diethyl malonate in the presence of a Lewis acid. From the reaction mixture, ethyl A-(3-chloro-4-fluorophenyl)-2-[(3-chloro-4-fluorophenyl)-aminomethylene]malonamate and A-(3-chloro-4-fluorophenyl)formanilide were also isolated as byproducts (88MI3). 

Arylazo-l-naphthylamines were first reacted with ethyl orthoformate in boiling xylene for 2 hr diethyl malonate and piperidine were then slowly added to the reaction mixture over a period of 15-20 min. The resulting... 

Reaction with reactive-methylene compounds. Claisen" developed a method for the preparation of diethyl ethoxymethylenemalonate by heating a mixture of triethyl orthoformate, malonic ester, and acetic anhydride with a catalytic amount of zinc chloride. The yield cited is that obtained in a standardized procedure."... 

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