Pyruvic acid phenylhydrazone

For the mechanism of this reaction, see Robinson and Robinson,1918, H3i 639 1924, 145, 827.) The reaction is of wide application for example, the use of methyl-phenyl-hydrazine, CsH5(CHj)> -iN H, in the above reaction gives i-methyl-2-phenylindole, whereas pyruvic acid, CH CO COOH, when converted to its phenylhydrazone and then indolised, gives indole-2-carboxylic... 

Ligand abbreviations bi = 2,2 -bi-2-imidazoline bt = 2,2 -bi-2-thiazoline bpy = 2,2 -bipyridine phen = 1,10-phenanthroline phy = l,10-phenanthroline-2-carbaldehyde phenylhydrazone bpp = 2,6-bis(pyrazol-3-yl)pyridine paptH = 2-(2-pyridylamino)-4-(2-pyridyl)thiazole 2-pic = 2-picolylamine L = macrocyclic ligand derived from condensation of 2,6-diacetylpyridine with 3,6-dioxaoctane-1,8-diamine Hjthpu = pyruvic acid thiosemicarbazone Hjthpx = pyridoxal thiosemicarbazone salen = dianion of W,iV -ethylenebis(salicylideneimine) H2fsa2en = dianion of fV,JV -ethylenebis(3-carboxysalicylaldimine). 

The mechanism of this elegant, surprising, and widely applicable synthesis of indole derivatives was only explained recently (R. Robinson). It must be assumed that the keto-phenylhydrazones, in tautomeric hydrazo-form, undergo a species of benzidine rearrangement which, like the latter, can often occur even in dilute acid solution, e.g. with the phenylhydrazone of pyruvic acid. 

Preparation 251.—Phenylhydrazone oi Pyruvic Acid [Propanon-add-phenylhydrazone]. 

Cleavage of—N—derivatives. This reagent is more effective than pyruvic acid for the cleavage of phenylhydrazones and semicarbazones. Reaction with a phenyl-hydrazone produces 3,5-dimethyl-N-phenylpyrazoIe and liberates the free carbonyl compound. 

Pyrrolidine, 552 4-Pyrrolidinopyridine, 112 Pyttolidone-2-hydrotribromide, 97 Pyruvaldchyde 2-phenylhydrazone, 500 Pyruvic acid, 493... 

A mixture of 4.53 g of-aminophenylacetic acid (0.03 mol), 7.9 g pyruvic acid (0.09 mol), and 200 mL water (3.5% deuterium) was boiled under reflux for 3 h. A homogeneous solution was formed within a few minutes after the mixture began to boil. On completion of the reaction, benzaldehyde was removed by distillation through a declining condenser and extracted from the distillate with several small portions of chloroform. The aqueous portion of the distillate and the aqueous reaction mixture were reserved. After drying the chloroform solution over sodium sulfate, the solvent was evaporated and the residual benzaldehyde was converted into the phenylhydrazone by treatment with phenylhydrazine in 50% alcoholic solution. After recrystallization from 60% alcohol, the yield of benzaldehyde phenylhydrazone was 4.3. 4 g, m.p. 155.5-157°C for various preparations. 

Another practicable synthesis of alanine has been described recently by Billman and Parker (97, 99). Alanine is prepared in 45% of the theo retical yield by permanganate oxidation of commercially available 2-ben> zoylamino-l-propanol and acid hydrolysis of the resulting benzoyl-alanine. Other syntheses which are of value for special purposes, such as the introduction of isotopic atoms into amino acid molecules, include the catalytic reduction of the phenylhydrazone of pyruvic acid (264,272,298) and of a-oximinopropionic acid (366, 718). 

DL-Isoleucine is synthesized in about 56% over-all yield by the method of Hamlin and Hartung (366). o-Oximino- -methyl-w-valeric acid (A) is prepared in 70% yield from ethyl sec.-bulyl acetoacetate, butyl nitrite and sulfuric acid. DL-Isoleucine is prepared in 80% yield by the reduction of (A) with hydrogen, palladium chloride and ethanol. This method is essentially the same as that originated by Bouveault and Locquin (117, 118, 525). By the comparable procedure of Feofilaktov (264, 265) the phenylhydrazone of methyl ethyl pyruvic acid, prepared from sec.-butyl acetoacetate and phenyldiazonium chloride (aniline and NaN02) in 68% yield, is reduced by means of rinc and alcoholic HCl to nearly the theoretical yield of a mixture of DL-isoleucine and DL-allo-isoleucine. Ehrlich (235) synthesized a mixture of isoleucine and allo-isoleucine from 2-methyl-n-butyraldehyde by the Strecker reaction. 

The phenylhydrazone of ethyl pyruvate on heating with sulfuric acid in acetic acid forms indole-2-carboxyIic acid (58%). When the phenylhydrazone has nuclear substituents like alkyl, halo, or nitro groups, the corresponding 4-, 5-, 6-, or 7-substituted indoles are obtained. When pbenylhydrazine is added to a boiling mixture of cyclohexanone and... 

When the Fischer synthesis is applied to an unsymmetrical ketone, either one of two isomers or a mixture of them may be produced. (+)-3-MethylcycIopen-tanone gives a mixture of I- and 2-methylcyclopent[0]indoles, and the relative amounts of these formed under various conditions are analysed [3222]. Further work has recently been published on the Fischer indolization of -methoxy-phenyl- -phenylhydrazones of an unsymmetrical ketone (ethyl pyruvate). Cyclization in acid occurs mostly on to the more electron-rich benzene ring whereas under nonacidic (for example, thermal) conditions there is less regio-selectivity [3539]. 2-Methoxyphenylhydrazine sometimes behaves anomalously and does not yield the expected 7-methoxyindole, but when o-4-toluenesuIphonyl-or o-4-trifluoromethylsulphonyI-phenylhydrazine is used to prepare the hydra-zone, the main product is the 7-sulphonyloxyindole which may be hydrolysed to the 7-hydroxyindole with alkali [3629]. 

Japp and Klingemann found that benzenediazonium salt 2 coupled with ethyl methylacetoacetate 1 in alkaline solution to give the phenylhydrazone of ethyl pyruvate 3 with elimination of acetic acid. However, if the ketonic ester was first hydrolyzed with alkali and then coupled, the product was monophenylhydrazone 10, with carbon dioxide being eliminated rather than acetic acid.6... 

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