A-Keto acid chlorides

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... 

Cyclization of Anhydrides. Instead of the acid chloride, an intramolecular anhydride of the type LXXIX may be used for cyclization by the Friedel-Crafts reaction (Table VII, examples marked by h ). This resembles the intermolecular acylation with succinic anhydride, and a similar procedure is generally followed. The product of ring closure is a keto acid LXXX. Nitrobenzene 9i 6,1120 is a generally effective solvent for the reaction sym-tetrachloroethane also may be used.121... 

The 5(2H)-oxazolones (213) present two sites, C(4) and C(5), to nucleophilic attack they usually react at the latter. The benzylidene derivative (214), the most thoroughly studied member of this class, possesses an additional electrophilic centre at the exocyclic carbon atom. However, alkaline hydrolysis of this compound affords phenylacetamide and benzoylformic acid by acyl-oxygen fission (equation 50). a-Keto acids are also obtained when 2-trifluoromethyl-5(4//)-oxazolones are hydrolyzed, the reaction involving preliminary isomerization to a 5(2//)-oxazolone. The example shown in equation (51) represents the first non-enzymatic synthesis of an optically active a-keto acid. An instance of nucleophilic attack at C(4) of a 5(2//)-oxazolone is the formation of the oxazolidinone (215) in a Grignard reaction (equation 52). However, the typical behaviour of unsaturated pseudooxazolones like (214) is conjugate addition of a nucleophile, followed by further transformations of the resulting 5(4F/)-oxazoIones. This is illustrated by the reaction of compound (214) with benzene in the presence of aluminum chloride to yield, after aqueous work-up, the acylamino acid (216 equation 53). 

Acetylenes, homologation to allenes, 63, 203 Acetylenes, in peptide synthesis, 63, 175 a,B-ACETYLENIC KETONES, ASYMETRIC REDUCTION OF, 63, 57 ACID CHLORIDES FROM a-KETO ACIDS, 61, 1 Acrolein [107-02-8], 62, 140... 

For the quantitative determination of Krebs cycle acids, Horning et al. [160] recommended methoxime-TMS esters. A 10-mg amount of methoxylammonium chloride is added to a solution of 1 mg of a keto acid (or a mixture of acids) in 0.5 ml of pyridine. After standing for 2-3 h, pyridine is removed with a stream of nitrogen and 0.2 ml of BSTFA is added to the residue containing methoxime and unreacted methoxylammonium chloride. After standing for 1—2 h at room temperature, 0.5—1.0 /al of the solution is taken directly for GC analysis. 

This vitamin acts as a coenzyme in the metabolism of carbohydrates and is present in all living tissues. It acts in the form of thiamin diphosphate in the decarboxylation of a-keto acids and is referred to as cocarboxylase. Thiamin is available in the form of its chloride or nitrate, and its structural formula is shown in Figure 9-12. The molecule contains two basic nitrogen atoms one is in the primary amino group, the other in the quater-... 

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

When a mixture of phthalic anhydride and an aryl hydrocarbon is acted upon by aluminum chloride, one of the acyl groups unites with the hydrocarbon radical, thus forming a keto acid. Benzene with phthalic anhydride forms o-benzoylbenzoic acid ... 

Sometimes the addition of a small amount of ZnCh as a catalyst is recommended, e.g. succinic acid is transformed to the dichloride only in the presence of this catalyst. It has to be noticed, however, that under these conditions hydrogen chloride is evolved and, therefore, acid sensitive compounds cannot be taken. Af-acylamino acid chlorides and chlorides of fully acetylated sugar acids are also obtainable in yields of 70% or more. Whereas most reagents seem to be unsuited to the preparation of acid halides of a-keto acids, dichloromethyl methyl ether is successful in this reaction (equation 10). Pyruvyl chloride can now be made in ca. 50% yield. In some examples the corresponding a,a-dibromomethyl methyl ether has also been tested. ... 

In a few examples it was demonstrated that diazonium salts are capable of coupling with amide chlorides in the a-position yielding hydrazones of a-keto acid amide chlorides (55 equation 34). ... 

The realization that doubly carbonylated products can be formed in carbonylation reactions has only emerged in the last ten years, but specific syntheses of many a-keto acids, amides, esters and related products are being developed rapidly. Although many such syntheses depend on the use of CO pressures well above ambient, variation of other parameters such as catalyst, solvent and base can lead to efficient double carbonylation even at relatively low pressures. Selective, cobalt-catalyzed formation of phenylpy-mvic acid (97% selectively at 85% yield) from benzyl chloride was thus achieved at 50 bar pressure of CO in propan-2-ol, but more recent work has shown that similar selectivity and an even higher yield can be obtained at less than 2 bar when 1,2-dimethoxyethane is used as solvent (equation 62). °°... 

Court have used for a synthesis of a cyclohexenone. Thus the vinylketene thioacetal (3) reacts with maleic anhydride in refluxing xylene (3 hr.) to give the adduct (4) in 60% yield. Hydrolysis of the dithioacetal group was effected with mercuric chloride in 90% aqueous methanol at reflux. The initial product (5), a / -keto acid, undergoes decar-... 

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