Acid, acetic hippuric

Several improved methods for the preparation of known unsaturated azlactones as well as some interesting new compounds of this type have been reported. Crawford and Little observed that the direct use of 2-phenyl-5-oxazolone (1) in the Erlenmeyer reaction gave much improved yields (35-74%) of unsaturated azlactones with aliphatic aldehydes and with ketones such as acetone and cyclohexanone [Eq, (1)], The usual procedure of mixing a carbonyl compound, hippuric acid, acetic anhydride, and sodium (or lead) acetate affords poor yields in the aliphatic series. 

The cited160,161 formation of polychloropyrans 120 -> 121 and 120 - 122 may be regarded as proceeding via 2-phenyl-3,4,5-trichloro- or 3,4,5-tri-chloropyrylium chlorides, which are attacked by a chloride ion. The transformation of pyrylium salts 219 to 4-formyl-4//-pyrans 220 with hippuric acid, acetic anhydride, and sodium acetate2651 is discussed in Section IV,J. 

The usual procedure of mixing a carbonyl compound, hippuric acid, acetic anhydride, and sodium (or lead) acetate affords poor yields in the aliphatic series. 

With a modified gradient program, starting with a lower initial chloride concentration and a more shallow gradient, some organic acids such as lactic acid, pyruvic acid, formic acid, acetic acid, malonic acid, hippuric acid, fiimaric acid. 

Gyanomethyl N-benzoylglycinate refluxed 20-40 hrs. with 1.2 moles of p-nitro-phenylhydrazine in ethyl acetate -> hippuric acid p-nitrophenylhydrazide. Y 90%.—Similar reactions with the analogous methyl esters failed. F. e. s. P. Grud-zinska, Roczniki Ghem. 34, 1687 (1960). 

When salicylaldehyde is heated with hippuric acid, acetic anhydride, and sodium acetate, benzoylaminocoumarin is obtained along with the acetoxyazlactone. Similar results are obtained with 2,4-dihy-... 

Thiazolecarboxaldehydes exhibit many reactions typical of aldehydes. However, they give no aldolization reaction (no a-hydrogen), but they do react with different compounds such as acetic anhydride, hippuric acid, acetylglycine, and so for (37, 101, 102). Thus 2-phenyl-4-fonnylthiazole (31) mixed with hippuric acid and treated with AcOa and anhydrous NaOAc gives the azalactone (32) (Scheme 32). 

This azlactone is prepared readily from benzaldehyde according to the procedure given for the azlactone of a-ben-zoylamino-/3-(3,4-dimethoxyphenyl)-acrylic acid (Org. Syn. 13, 8). From 53 g. (0.5 mole) of benzaldehyde, 89.5 g. (0.5 mole) of hippuric acid, 41 g. of fused sodium acetate, and 153 g. of acetic anhydride there is obtained 78-80 g. (62-64 per cent yield) of an almost pure product melting at 165-166° (corr.). This material is sufficiently pure for use in the preparation of phenylalanine. By crystallization from 150 cc. of benzene a product melting at 167-168° (corr.) is obtained. 

The azlactones of a-benzoylaminocinnamic acids have traditionally been prepared by the action of hippuric acid (1, Ri = Ph) and acetic anhydride upon aromatic aldehydes, usually in the presence of sodium acetate. The formation of the oxazolone (2) in Erlenmeyer-Plochl synthesis is supported by good evidence. The method is a way to important intermediate products used in the synthesis of a-amino acids, peptides and related compounds. The aldol condensation reaction of azlactones (2) with carbonyl compounds is often followed by hydrolysis to provide unsaturated a-acylamino acid (4). Reduction yields the corresponding amino acid (6), while drastic hydrolysis gives the a-0X0 acid (5). ... 

The reaction of hippuric acid with a three-fold excess of trifluoro-acetic anhydride gives a 90% yield of 2-phenyl-4-(2, 2, 2 -trifluoro-l -hydroxyethylidene)-5-oxazolone (2). This compound is also obtained... 

The isolation of several pairs of geometric isomers of 4-unsaturated-5-oxazolones has been described. Generally, only one isomer is obtained when an aldehyde reacts with hippuric acid in the presence of acetic anhydride. Occasionally, mixtures have been separated in base-catalyzed reactions. In acetic anhydride-sulfuric acid or in 100% sulfuric acid, a mixture is obtained, and it has been suggested that sulfuric acid inhibits mutarotation of the intermediate addition product 53, which is a mixture of diastereomers (see, e.g., compound... 

A mixture of 537 g (3 moles) of hippuric acid (Note 1) and 16 1 (17 moles) of acetic anhydride is prepared in a 3 1. threenecked, round-bottomed flask fitted with a sealed stirrer, a reflux condenser with a drying tube, a thermometer, and a nitrogen inlet tube (Note 2)... 

Acetic anhydride, condensation with and acetylation of glycine, 46, 1 in cyclization of c-formylphenoxy-acetic acid to coumarone, 46, 28 in cyclization of hippuric acid to 2-phenyl-5-oxazolone, 47, 101 reaction with N-nitroso-N-phenyl-glycine to yield 3-phenylsydnone, 46,96... 

Hippuric acid, cyclization to 2 phenyl-5 oxazolone with acetic anhydride, 47,101 Holarrhimine, 46, 61 Hydrazine, reaction with cinnamalde-hyde, 47, 99... 

The methylene groups of hippuric acid and malonic acid are much more reactive than that of acetic acid. They may be caused, therefore, to condense with aldehydes under much milder conditions, e.g. by the action of pyridine. The use of malonic acid forms an extension of Perkin s reaction to the aliphatic series (Doebner), e.g. 

Three synthetic approaches for benzopyrones have been developed that use Gly as starting material. Hippuric acid was transformed with acetic anhydride into 2-phenyl-5(4//)oxazolone or further into its 4-ethoxy-methylene derivative, then reacted with cyclic 1,3-dicarbonyI compounds (such as like dimedone) to form 100 [90LA501 92H(33)843]. On the other hand, when hippuric acid was transformed into methyl 2-benzoyl-amino-3-dimethylaminopropenoate, it reacted with resorcinol to give a 7-hydroxybenzopyrone derivative (89JHC1273). 

When benzaldehyde is condensed with hippuric acid in the presence of acetic anhydride a Perkin s reaction takes place and benzoyl-a-amido-cinnamic acid is formed —... 

Erlenmeyer jun., and Halsey, in 1899, synthesised tyrosine by the condensation of hippuric acid with p-oxybenzaldehyde in the presence of acetic anhydride. The reactions are the same as those described by Erlenmeyer for the synthesis of phenylalanine, except that the hydroxyl group of the p-oxybenzaldehyde becomes acetylated in the process —... 

Condensation of A -acylglycines with carbonyl compounds, the Erlenmeyer synthesis, continues to be exploited to prepare of a wide variety of unsaturated-5(47/)-oxazolones. The reaction is performed in the presence of a cyclodehydrating agent and recently bismuth(lll) acetate has been evaluated in this capacity. Alternatively, unsaturated 5(47/)-oxazolones can be obtained from hippuric acid and a carbonyl compound or from the appropriate dehydroamino acid derivative using 3-(aIkoxycarbonyl)benzotriazole-l-oxides as the cyclodehydrating agent. 

The condensation of furo[3,2- ]pyrrole-type aldehydes 8g and 265-267 with hippuric acid was carried out in dry acetic anhydride catalyzed by potassium acetate as is shown in Scheme 26. The product methyl and ethyl 2-[( )-(5-oxo-2-phenyl-l,3-oxazol-5(4//)-ylidene)methyl]furo[3,2- ]pyrrol-5-carboxylates 268a-d were obtained. The course of the reaction was compared with the reaction of 5-arylated furan-2-carbaldehydes with hippuric acid. It was found that the carbonyl group attached at G-2 of the fused system 8 is less reactive than the carbonyl group in 5-arylated furan-2-carbaldehydes in this reaction <2004MOL11>. The configuration of the carbon-carbon double bond was determined using two-dimensional (2-D) NMR spectroscopic measurements and confirmed the (E) configuration of the products. 

The metabolism of benzyl acetate involves very rapid hydrolysis to acetate and benzyl alcohol. The latter is subsequently mainly oxidized to benzaldehyde and benzoic acid. A small part of the benzyl alcohol may be conjugated with sulfate, leading, ultimately, to fonnation of a glutathione conjugate that is excreted as mercapturate in urine. The benzoic acid is excreted mainly as hippurate and, to a lesser extent, as acyl glucuronide (see Figure 1). 

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