Aromatic acids Ring-carboxy

S3mthesis of Ring Carboxy Acids.—We have just discussed the synthesis of aromatic acids by the oxidation of benzene hydrocarbons containing a side chain. As would be expected from our description... 

From Hydrocarbons, Friedel-Craft.—The aromatic hydrocarbons yield ring carboxy acids by other reactions than those effecting oxidation of a side chain. Carbon dioxide may be introduced directly into a benzene ring, thus converting a hydrogen into.carboxyl. This may be accomplished in the presence of aluminium chloride, Friedel-Craft reagent. 

From Aryl Halides. Kekule Synthesis.—Aromatic halides in which the halogen is in the ring yield ring carboxy acids by the action of carbon dioxide and sodium. 

Ring Carboxy Acids by the Grignard Reaction.— Aromatic acids with carboxyl in the ring may also be prepared by the Grignard reaction... 

HYDROXY AROMATIC ACIDS PHENOL RING-CARBOXY ACIDS... 

With Sulfur Nucleophiles N-Carboxy-protected aziridine-2-carboxylates react with thiols to give P-mercapto-ot-amino acid derivatives. The reaction is usually catalyzed by BF3 and the yields range from fair to excellent [15, 16, 108-111]. With N-unprotected 3-substituted aziridine-2-carboxylates, the ring-opening with thiols usually takes place with anti stereoselectivity, especially in the case of the C-3 aliphatic substituted substrates. In cases in which C-3 is aromatic, however, the stereoselectivity has been found to be a function of the substitution pattern on the aromatic ring 3-p-methoxy ph eri yl-su bs li In led aziridines 143a (Scheme 3.51) and... 

The ionization of (E)-diazo methyl ethers is catalyzed by the general acid mechanism, as shown by Broxton and Stray (1980, 1982) using acetic acid and six other aliphatic and aromatic carboxylic acids. The observation of general acid catalysis is evidence that proton transfer occurs in the rate-determining part of the reaction (Scheme 6-5). The Bronsted a value is 0.32, which indicates that in the transition state the proton is still closer to the carboxylic acid than to the oxygen atom of the methanol to be formed. If the benzene ring of the diazo ether (Ar in Scheme 6-5) contains a carboxy group in the 2-position, intramolecular acid catalysis is observed (Broxton and McLeish, 1983). 

The IR spectra are useful for detecting functional groups of Aristolochia alkaloids. Aristolochic acids show two characteristic bands at 1550 and 1350 cm due to the absorption of nitro group, and the carboxy OH group appears at 3000-2500 cm as a broad continuous absorption. Hydroxy derivatives of aristolochic acids or aristolactams show OH and NH absorptions at 3300-3500 and 3200-3400 cm The carboxy or lactam carbonyl is present at 1690 cm i. In general, the aromatic ring system shows stretches at 1625-1575 and 1525-1475 cm 1 as usual, and observation of the 900-700 cm region is often used for analysis of substitution type in aromatic derivatives 28). 

The benzene ring has been proposed as an isosteric replacement in a dipeptide to enforce either the tram l1 1 or the cis conformation 312>31 (Scheme 1). Similarly, 2-(amino-methyl)pyrrole-l-acetic acid (8, R = H) has been proposed as a cis peptide bond mimic,141 having the same number of atoms between the amino and carboxylic acid functions as in a dipeptide. Several other amino- and carboxy-substituted aromatic structures have been used as spacers in peptides 2-, 3-, and 4-aminobenzoic acids (Abz, e.g., 7), 2-, 3-, and 4-(amino-methyl)benzoic acids (Amb, e.g., 2), 2-, 3-, and 4-(aminophenyl)acetic acids (APha, e.g., 5), 2- (4), 3-, and 4-(aminomethylphenyl)acetic acid (Ampa), (aminomethyl)pyrrole-, -thiophene-, and -furancarboxylic acids 6, (aminomethyl)pyrrole- 8 and -thienylacetic acids, and aminobiphenylcarboxylic acids. 

Overheating in the acid solution causes cyclization of the amide oxygen atom on to the carboxy lic acid. This reaction happens only because of the formation of a five-membered ring, an azlactone. These compounds are particularly dreaded by amino acid chemists because they racemize easily b . enolization and the enol is an aromatic compound. 

In order to obtain cyclization of an N-a-carboxy dithiocarbamic acid (CLXXXI) to the thiazolidin-5-one-2-thione (CLXIII), dehydrating agents are necessary. These same products may, however, be obtained by simply warming the a-amino carboxylic acid esters with carbon disulfide, especially when there is an aromatic ring attached to the -carbon atom (method D). In this way a-(methylamino) phenylacetic acid and carbon disulfide yield 3-methyl-4-phenylthiazolidin-5-one-2-thione [121) (Table 24). 

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