P-Aminobcnzoic acid

Some hetcrocycles are simple, some very complex, but we cannot live without them. We shall end this chapter with a wonderful story of heterocyclic chemistry at work. Folic acid is much in the news today as a vitamin that is particularly important for pregnant mothers, but that is involved in the metabolism of all living things. Folic acid is built up in nature from three pieces a heterocyclic starting material (red), p-aminobcnzoic acid (black) and the amino acid glutamic acid (green). Here you see the precursor, dihydrofolic acid. 

Hydrogenation of p-aminobcnzoic acid to a mixture of cis- and fran.s-4-aminocy-clohexanecarboxylic acid was successful with the use of a Rh-Pd-C catalyst (10% Rh-0.1% Pd) in water at room temperature and a low hydrogen pressure (eq. 11,65).222 The cis isomer of the amino acid was further converted to 3-isoquinuclidone (2-azabicyclo[2.2.2]octan-3-one] (23) by heating in boiling Dowtherm A (258°C). 

Folic acid is a pteridine derivative (rings A and B constitute the pteridine heterocyclic system) synthesized by bacteria from GTP, p-aminobenzoic acid, and glutamic acid. Accordingly. the structure of folic acid is compased of three moieties the pteridine moiety derived from GTP. the p-aminobcnzoic acid moiety, and the glutamic acid moiety. (Antibacterial sulfonamides [see Chapter 8 compete with p-aminobenzoic acid and, thereby, interfere with bacterial folic acid synthesis.) Humans cannot synthesize folic acid. 

D. p-Aminobcnzoic acid Bacteria Higher animals, insects, lower fungi ... 

Ethyl -aminobenzoate has been prepared by the esterification of p-aminobcnzoic acid1 and by the reduction of ethyl /i-nitrobenzoate with ammonium sulfide.2 Although commer-dally the reagent used is usually iron and water in presence of a little acid, in the laboratory the catalytic reduction as described in the procedure is by far the most convenient. 

Theory Folic acid (I) undergoes cleavage by reduction with Zn-Hg in acidic medium to yield p-aminobenzoylglutamic acid (II). The primary aromatic amino group present in the latter is subsequently diazotized in the usual manner and coupled in acidic solution with N-(l-naphthyl)-ethylenediamine hydrochloride in the absence of light (caution). The colour thus produced has a maximum absorption at 550 nm and the extinction (E) is consequently compared with a calibration curve obtained from / -aminobcnzoic acid (PABA) that has been duly diazotized and coupled exactly in the same fashion as the/ -aminobcnzoylglutamic acid. 

Iodobenzoic acid has been prepared by the oxidation of -iodotoluene with chromic acid mixture 1 and with nitric acid 2 from the nitrile obtained from p-iodonilrobenzene and potassium cyanide 3 and from />-aminobcnzoic acid by diazotization.4... 

Carboxyphenyl Phenyl Tellurium2 27.2 g (0.2 mol) of 2-aminobcnzoic acid arc dissolved in a mixture of 25 ml of concentrated hydrochloric acid and 70 ml of water. 13.8 g of sodium nitrite dissolved in 20 ml of water are added dropwisc to the stirred amine solution cooled in an icc/walcr bath. Sodium hydrogen carbonate is added until the solution of the diazonium salt is slightly basic. 23 g (56 mmol) of diphenyl ditellurium are dissolved in a mixture of 30 ml of ethanol and 60 ml of THF. To this solution are added 2.3 g (60 mmol) of sodium borohydride dissolved in 33 ml of 1 M aqueous sodium hydroxide. The diazonium salt solution is quickly added to the warm benzenetellurolate solution. 10 ml of 1 M sodium hydroxide are then added and, after the evolution of nitrogen has ceased, the mixture is heated to complete the reaction. The mixture is poured onto ice and diphenyl ditellurium is extracted with benzene. The aqueous phase is acidified with 1 M hydrochloric acid and the product precipitates in analytically pure form yield 28.2 g (43%) m.p. 185° (from toluene). 

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