PYRUVOYL CHLORIDE

Although the formation of symmetric piperazine-2,5-diones is a well documented transformation (93AHC187), the unsymmetric -ones have been prepared from AAs or their amides with acyl halides, such as pyruvoyl chloride (81RTC73) and a-bromopropionyl bromide (91H923). 

At this temperature the intermediate, chloromethoxymethyl pyruvate, decomposes to pyruvoyl chloride and methyl formate.4... 

ACID CHLORIDES FROM ot-KETO ACIDS WITH a,a-DICHLOROMETHYL METHYL ETHER PYRUVOYL CHLORIDE... 

The submitters found that pyruvoyl chloride may be stored at — 20°C in carbon tetrachloride solution or as the pure liquid in a sealed tube. 

Most of the conventional reagents for the synthesis of acid chlorides from carboxylic acids are unsatisfactory for the preparation of a-keto acid chlorides. For example, the reaction of pyruvic acid with phosphorus halides does not give pyruvoyl chloride7 whereas the use of phosgene8 or oxalyl chloride9,10 affords ether solutions of the acid chloride in low yield. Recently a useful preparation of pyruvoyl chloride from trimeth-ylsilyl pyruvate and oxalyl chloride has been described.11... 

The use of a,a-dichloromethyl alkyl ethers for the conversion of carboxylic acids to acid chlorides was first reported by Heslinga et al. in 1957.4 The submitters have found that the readily available a,a-dichlo-romethyl methyl ether2 is the reagent of choice for the preparation of pyruvoyl chloride.6 This simple and economical procedure has been used in other laboratories,51213 and the submitters have applied the method to the preparation of three other a-keto acid chlorides 2-oxobutanoyl chloride (32%), 3-methyl-2-oxobutanoyl chloride (10%), and phenylglyoxylyl chloride (78%).6... 

The synthesis of PYRUVOYL CHLORIDE from the corresponding acid not only represents the method of choice for the preparation of this substance, but can be applied to other acids as well. A one-pot procedure for the preparation of ETHYL 2-BUTYRYLACETATE illustrates another general method for the synthesis of /J-ketoesters. The synthesis of 4-PENTYLBENZOYL CHLORIDE by direct electrophilic substitution of 4-pentylbenzene with phosgene, derived in situ from oxalyl chloride, can likewise be applied to other aromatic substrates. 

The second mode of (4 + 2) addition uses an a-dicarbonyl compound to form C-3 and C-4. This can be oxalyl chloride <67JOC4072> or diethyl oxalate <89TL3551>, as in the synthesis of compounds (170) (Equation (163)) and (108) (Equation (164)) or pyruvoyl chloride, as in the synthesis of compound (320) (Equation (165)) <86EUP180544>. 

Oxalyl chloride added portionwise to trimethylsilyl pyruvate containing some dimethylformamide, after 0.5 hr. distilled at 50°/12mm pyruvoyl chloride. Y 45-80%. J. Hausler und U. Schmidt, B. 107, 145 (1974). 

By addition of pyruvoyl chloride to a-iminocarboxylic acid derivatives 295a, 295b, 311). 

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