2- -benzoic acids, ring

Keywords 2-aminobenzamide, o-phenylenediamine, benzoic acid, ring closure, melt reaction, benzimidazole, quinazolinone... 

Soil/Environment. DT50 4—10 days undergoing loss of chlorine from the benzoic acid ring... 

Ruell, J. A., De Clercq, E., Pannecouque, C., Witvrouw, M., Stup, T. L., Turpin, J. A., Buckheit, R. W., Jr., Cushman, M. Synthesis and Anti-HIV Activity of Cosalane Analogues with Substituted Benzoic Acid Rings Attached to the Pharmacophore through Methylene and Amide Linkers. J. Org. Chem. 1999, 64, 5858-5866. 

Anthranilic acid. This substance, the ortho amino derivative of benzoic acid, may be conveniently prepared by the action of sodium hypobromite (or sodium hypochlorite) solution upon phthalimide in alkaline solution at 80°. The ring in phthalimide is opened by hydrolysis to phthalamidic acid and the latter undergoes the Hofmann reaction (compare Section 111,116) ... 

The best-known equation of the type mentioned is, of course, Hammett s equation. It correlates, with considerable precision, rate and equilibrium constants for a large number of reactions occurring in the side chains of m- and p-substituted aromatic compounds, but fails badly for electrophilic substitution into the aromatic ring (except at wi-positions) and for certain reactions in side chains in which there is considerable mesomeric interaction between the side chain and the ring during the course of reaction. This failure arises because Hammett s original model reaction (the ionization of substituted benzoic acids) does not take account of the direct resonance interactions between a substituent and the site of reaction. This sort of interaction in the electrophilic substitutions of anisole is depicted in the following resonance structures, which show the transition state to be stabilized by direct resonance with the substituent ... 

Alkyl groups attached to aromatic rings are oxidized more readily than the ring in alkaline media. Complete oxidation to benzoic acids usually occurs with nonspecific oxidants such as KMnO, but activated tertiary carbon atoms can be oxidized to the corresponding alcohols (R. Stewart, 1965 D. Arndt, 1975). With mercury(ll) acetate, allyiic and benzylic oxidations are aJso possible. It is most widely used in the mild dehydrogenation of tertiary amines to give, enamines or heteroarenes (M. Shamma, 1970 H. Arzoumanian. 1971 A. Friedrich, 1975). 

Pyrrole Carboxylic Acids and Esters. The acids are considerably less stable than benzoic acid and often decarboxylate readily on heating. However, electron-withdrawing substituents tend to stabilize them toward decarboxylation. The pyrrole esters are important synthetically because they stabilize the ring and may also act as protecting groups. Thus, the esters can be utilized synthetically and then hydrolyzed to the acid, which can be decarboxylated by heating. Often P-esters are hydrolyzed more easily than the a-esters. 

Animals caimot synthesize the naphthoquinone ring of vitamin K, but necessary quantities are obtained by ingestion and from manufacture by intestinal flora. In plants and bacteria, the desired naphthoquinone ring is synthesized from 2-oxoglutaric acid (12) and shikimic acid (13) (71,72). Chorismic acid (14) reacts with a putative succinic semialdehyde TPP anion to form o-succinyl benzoic acid (73,74). In a second step, ortho-succmY benzoic acid is converted to the key intermediate, l,4-dihydroxy-2-naphthoic acid. Prenylation with phytyl pyrophosphate is followed by decarboxylation and methylation to complete the biosynthesis (75). 

In its chemical behavior benzoic acid shows few exceptional properties the reactions of the carboxyl group are normal, and ring substitutions take place as would be predicted. 

Chlotobenzoyl)-benzoic acid is nitrated in concentrated sulfuric acid, then reduction of the nitro group, ring closure, and hydrolysis occur simultaneously in concentrated sulfuric acid in the presence of a reducing agent and boric acid. Thus obtained cmde chloro pink is purified by selective precipitation from sulfuric acid in order to separate it from by-produced 2-amino-3-chloto-l-hydroxyanthtaquinone (24) (36). 

Pyridazinecarboxylic acids are more acidic than benzoic acids, due to the electronegativity of the pyridazine ring, but oxopyridazinecarboxylic acids are weaker than the corresponding pyridazinecarboxylic acids (Table 11). 

The reaction of 2-phenyl-l-azirine (201) with benzoic acid gaveN-benzoylphenacylamine (204) (67BCJ2938). The overall mechanism of the reaction involves initial protonation on nitrogen followed by addition of the nucleophile to the azirinium ion and finally ring opening. 

Heteratisine, C22H33O5N, crystallises in prisms, has m.p. 262-7° (dec.), [a]f7° + 40° (MeOH), forms a hydrochloride, m.p. 265-270° (dec.), contains one methoxyl and one methylimino group, two active hydrogens and a lactone ring, opened by alkali and re-formed on acidification. In a later paper the same authors describe the isolation of benzoylheteratisine, C29H3,03N, m.p. 213-4°, [a]jf° + 73° (EtOH), which yields a hydrochloride, m.p. 218-221° (dec.), and is hydrolysed to benzoic acid and heteratisine the latter they suggest may not exist naturally in the plant but may be produced from benzoylheteratisine during extraction. 

The reduction of a benzenoid ring, except in benzoic acid derivatives, occurs only in the presence of a proton donor having a pKa of 19 or less (pKa of ammonia is about 33). With the exception of the vinyl group, the other functional groups listed above do not require a proton donor of this acidity in order to be reduced, although the course of reduction may then be complex, e.g. as with esters. " Consequently, a variety of functional groups should be capable of selective reduction in the presence of a benzenoid ring if the reaction medium does not contain an acid of pKa <19. A few examples of such selective reductions have been reported in the steroid literature. 

On the other hand, an alkyl side chain on a benzene ring is oxidized on being heated with chromic acid. The product is benzoic acid or a substituted derivative of benzoic acid. 

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