Malonic anhydrides mixed

Because malonic anhydrides are difficultly accessible, Staudinger recommended the decomposition of mixed anhydrides as a generally applicable method these mixed anhydrides can be obtained by the action of, e.g., di-phenylketene on disubstituted malonic acids in ethereal solution.25... 

A method of synthesis of ketoketenes which is closely related to the pyrolysis described in the preceding section consists in the thermal decomposition of disubstituted malonic anhydrides, of either the simple or mixed types. 

Dimethylketene has beep obtained in unspecified yield by heating the monochloride of dimethylmalonic acid it is probable that the malonic anhydride was formed as an intermediate. This method failed in attempted applications to diethylketene, and carbon suboxide. Low yields of carbon suboxide have been obtained by tteating malonyl chloride with lead, silver, or zinc oxide or with silver oxalate or malonate, and by treating silver malonate with cinnamoyl chloride malonic anhydrides or mixed anhydrides may be intermediates. 

The acetic anhydride-induced cyclodehydration of the symmetrical diamide 411, derived from the tetrahydro-benzothiophene / -amino ester 410 and diethyl malonate, afforded the thieno[2,3-r7 [h3]oxazine derivative 413 rather than the expected bis-oxazine 412 (Scheme 78). The reaction probably takes place through sequential cyclizations, in which the pyridine ring of 413 is produced by condensation of the exocyclic double bond of the enamine tautomeric form of the 1,3-oxazine moiety and the mixed anhydride formed by the carboxylic group and acetic anhydride <2003PS245>. 

They are easily prepared from Grignard reagents, magnesium ethoxide or with the complex magnesium chloride-trialkylamine (see Section II where the generation of these reagents is discussed). The acylation of anions derived from malonates can be achieved with acyl chlorides, acyl imidazoles, aUcoxycarbonylimidazoles or mixed anhydrides. 

Pyrrole- and indole-carboxylic acid chlorides react with dialkyl- and diaryl-cadmium to yield the ketones and it is noteworthy that the reaction of the anhydride of indole-2,3-dicarboxylic acid with diphenylcadmium produces 3-benzoylindole-2-carboxylic acid and not its isomer (53JCS1889). The ability of l-methylindole-2-carboxylic acid to react with nucleophiles is enhanced by conversion into the mixed anhydride with methanesulfonic acid. The mixed anhydride reacts with carbanions derived from diethyl malonate and from methyl acetate to yield the indolyl (3- keto esters (80TL1957). 

A second procedure consists in heating mixed anhydrides prepared from disubstituted malonic acids and diphenylketene. 

The mixed anhydride method is analogously and conveniently applied to the preparation of a-amino acids (60) from malonic acid half-esters (59 equations 38 and 39). - ... 

Mixed anhydride synthesis. For use of the reagent in peptide synthesis, see Butyl chloroformate. The principle involved is illustrated by a procedure for the preparation of diethyl benzoylmalonate (3). Benzoic acid is condensed with cathyl chloride in toluene in the presence of triethylamine to produce the mixed anhydride (I), and an ethereal solution of ethoxymagnesium malonic ester (2), prepared from mulunic ester, magnesium, ethanol, and a trace of carbon tetrachloride as catalyst, is added... 

Mixed anhydride synthesis. A method widfely used for the synthesis of peptides provides a general method of acylation, illustrated by the benzoylation of diethyl malonate. Benzoic acid is converted into the triethylamine salt in toluene, and the solution is treated at 0 with ethyl chloroformate to form the mixed benzoic-carbonic anhydride, with precipitation of triethylamine hydrochloride. The second component, ethoxymagnesium malonic ester, is prepared from diethyl malonate in ethanol-ether... 

Diethyl benzoylmalonate has been prepared by treatment of the copper derivative of ethyl benzoylacetate with ethyl chlorocarbonate.9 It has also been obtained by the action of benzoyl chloride on a mixture of malonic ester and sodium ethoxide 1benzoyl chloride and the ethoxymagnesium derivative.14 The present method has been described in a previous communication and is of interest as an illustration of the use of mixed carbonic anhydrides as acylating agents.8... 

The decarboxylation of mixed anhydrides of malonic acids with phenyl-acetic acid is related to the decarboxylating acylation of arylacetic acids,26 of which the following is an example ... 

Malonic esters are desymmetrized by exchange of one of the ester groups, and chiral carboxylic esters are obtained from lipase-mediated alcoholysis of mixed carboxylic carbonic anhydrides. ... 

Type I dicarboxyltes the main product was PhCOOH (70 80%) and the minor product was (PhCO)20. Neither mono- nor bis-(mixed anhydride) products were detected. They included oxalate, malonate, maleate, and succinate. 

Several routes to /3-keto-acids, -esters, and -nitriles, based on the acylation of malonate derivatives, have been reported. The dianion of monoethyl malonate is acylated by acid chlorides to give -keto-esters in a one-pot synthesis,and the lithio-derivative of bis(trimethylsilyl) malonate reacts with acid chlorides, giving /3-keto-acids directly.The magnesium derivatives of monomethyl or mono-thioalkyl esters of malonic acid give j8-keto-esters or -thioesters respectively in high yield under virtually neutral conditions with acid imidazolides. Similarly, the trimethylsilyl ester of cyanoacetic acid, after lithiation, reacts with mixed anhydrides to give high yields of j8-keto-nitriles. ... 

A parallel study of the isotope-exchange reactions of malonate ion in Na0D-D20 has shown that the rate of exchange of malonate in D2O decreases to a minimum and then increases with increased [NaOD]." The oxidation of y,5-unsaturated acids to lactones with H2O2 is catalysed by methyltrioxorhenium a concerted mechanism is proposed. The activation of carboxylic acids by carbonates has been reviewed (79 references). Among the topics discussed is the esterification of A-protected amino acids (46) using di-f-butyl carbonate (47) " the putative active intermediate is the mixed anhydride (48). The reaction between maleic anhydride and f-butyl... 

A more common method involves the decomposition of mixed anhydrides, nearly all of which have been obtained by treating the dialkyl-malonic Acid, dissolved in dry ether, with diphenylketene. The resulting mixed anhydrides, derived from the malonic acids and diphenylacetic acid, are nearly insoluble in ether and separate in almost quantitative yields. They are decomposed by heating under diminished pressure untU... 

B. From Mixed Anhydrides Prepared from Malonic Adds and Diphenylkdene... 

It has been reported that the reaction of aromatic compounds with sodium palladium(II) malonate in a mixed solvent of acetic acids and acetic anhydride or carbon tetrachloride gives aromatic acids in good yields, together with lower yields of aromatic dimers. 

Carboxylic acid triethylamine salts yield mixed anhydrides which, when treated with ethoxymagnesiomalonic esters give the benzoylated malonate. Alternatively, treatment of the mixed anhydrides with sodium tetracarbonylferrate(II) produces the aldehyde derived from the parent aliphatic or aromatic carboxylic acid in good yield. ... 

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