2-Fluorobenzoic acid

In a 5-I. round-bottomed flask are placed 165 g. (1 mole) of ethyl / -aminobenzoate (Coll. Vol. 1, 235), 300 cc. of water, and 204 cc. (2.5 moles) of concentrated hydrochloric acid (sp. gr. 1.19) (Note 1). This mixture is warmed on a steam bath for an hour with occasional shaking. The flask containing the resulting white paste of / -carbethoxyaniline hydrochloride is placed in an ice-salt bath and cooled to o°. The mixture is stirred mechanically, and a solution of 72.6 g. (1 mole) of 95 per cent sodium nitrite in a minimum quantity of water is run in slowly while the temperature is kept below 70. The diazotization is complete when a faint positive test for nitrous acid with starch-iodide paper persists for ten minutes. 

While the diazotization is in process, 68 g. (x.i moles) of boric acid is dissolved in 133 g. (4 moles) of 60 per cent hydro-fluoric acid (Note 2) in a beaker coated with paraffin-wax. The temperature is kept below 250 to avoid melting the paraffin-wax (Note 3). 

The ice-cold fluoboric acid solution (Note 4) is added rather rapidly, with stirring, to the diazonium solution while the temperature is kept below io°. A thick paste of -carbethoxyben-zenediazonium fluoborate precipitates stirring is continued for twenty to thirty minutes. The solid is filtered on an 18.5-cm. Buchner funnel and washed consecutively with 300 cc. of cold water, 300 cc. of commercial methyl alcohol, and 200 cc. of commercial ether it is sucked as dry as possible between washings. The fluoborate is then dried over concentrated sulfuric acid (sp. gr. 1.84) in a vacuum desiccator (Note 5). The yield of the dried fluoborate is 198-205 g. (75-78 per cent of the theoretical amount) the decomposition point is 93-940. 

To purify the -fluorobenzoic acid, it is dissolved in hot dilute potassium carbonate solution (40 g. in 400 cc.) and the solution is treated with norite (decolorizing carbon) and filtered hot. Hydrochloric acid is added with stirring to precipitate the fluoro-benzoic acid, which is then cooled, filtered, and dried. 

When 85 g. (0.32 mole) of -carbethoxybenzenediazonium fluoborate is thus decomposed, there is obtajned 38-40 g. of -fluorobenzoic acid (84-89 per cent of the theoretical amount, based on the fluoborate 63-69 per cent, based on the ester of / -aminobenzoic acid). The melting point of the purified acid is 1860. The crude acid melts at 183-184°. 

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Alkaline hydrolysis of pentafluorobenzoic acid, the probable intermediate in the alkaline hydrolysis of perfluorotoluene, gives a high yield of p-hydroxytetra fluorobenzoic acid [9, 10 (equation 10)... 

CfiH3N02S 874-84-0) see Temocapril 2-nitro 5-fluorobenzoic acid (C7H4FNO4 320-98-9) see Flumazenil... 

Schreiber A, M Hellwig, E Dorn, W Reineke, H-J Knackmuss (1980) Critical reactions in fluorobenzoic acid degradation by Pseudomonas sp. B13 Appl Environ Microbiol 39 58-67. 

Goldman P, GWA Milne, MT Pignataro (1967) Fluorine containing metabolites formed from 2-fluorobenzoic acid by Pseudomonas species. Arch Biochem Biophys 118 178-184. 

Harper DB, ER Blakley (1971c) The metabolism of 7>-fluorobenzoic acid by a Pseudomonas sp. Can J Microbiol 17 1015-1023. 

Milne GWA, P Goldman, JL Holzman (1968) The metabolism of 2-fluorobenzoic acid. J Biol Chem 243 5374-5376. 

N,N-Dimethylacetamide (DMAc), 4-fluorobenzoic acid, 4-fluorobenzoyl chloride, aluminum chloride, 1 -bromonaphthalene, nitrobenzene, ferric chloride, dimethyl sulfone, 4,4 -dihydroxybiphenyl (DHB), and potassium carbonate were obtained from Aldrich and used without purification. 4,4-(Hexafluoroiso-propylidiene)-diphenol (6F-BPA), 9,9-bis(4-hydroxyphenyl)fluorene (HPF), and l,l-bis(4-hydroxyphenyl)-l-phenylethane (Bisphenol AP) were obtained from Ken Seika Corporation and used without purification. 4,4 -Dihydroxydiphenyl sulfone (DHDS) was obtained from Nachem Incorporated and used without purification. 

J. D. Cox, H. A. Gundry, A. J. Head. Thermodynamic Properties of Fluorine Compounds. Part 1. Heats of Combustion ofp-Fluorobenzoic Acid, Pentafluorobenzoic Acid, Hexafluorobenzene, and Decafluorocyclohexene. Trans. Faraday Soc. 1964, 60, 653-665. 

The new method of Yoneda s group132 is also a one-pot diazotization-fluoro-de-diazoniation in a liquid-liquid two-phase mixture of pyridine and hydrogen fluoride. Yields for 25 aromatic amines and diamines are 50-100%, except for 2-and 3-fluorobenzoic acid, the three nitroanilines, 3- and 4-diaminobenzene and 4,4 -diaminodiphenyl-oxide (10-50%). In their 1994 paper the authors demonstrate that, in the same system, the photochemical decomposition gives in many cases significantly higher yields than the thermal reaction. The most spectacular increase in yield was found for the fluorination of 2-fluoroaniline where o-difluorobenzene was obtained photochemically in 80.2% yield, but thermally only in 0.6% ... 

Fig. 3.4 Relationship between the stability constant, Pioi, for formation of SmL and the acid constant, of HL (1) propionic acid (2) acetic acid (3) iodoacetic acid (4) chloroacetic acid (5) benzoic acid (6) 4-fluorobenzoic acid (7) 3-fluorobenzoic acid and (8) 3-nitrobenzoic acid. 

Conversion of toluenes to the benzoic acid is also accomplished by anodic oxidation in acetic acid containing some nitric acid. It is not clear if this reaction involves the aromatic radical-cation or if the oxidising agents are nitrogen oxide radicals generated by electron transfer from nitrate ions [66, 67]. Oxidation of 4-fluorotoluene at a lead dioxide anode in dilute sulphuric acid gives 4-fluorobenzoic acid in a reaction which involves loss of a proton from the aromatic radical-cation and them in further oxidation of the benzyl radical formed [68]. 

AMINO-3-FLUOROBENZOIC ACID [Benzoic acid, 2-amino-3-fluoro-]... 

Amino-3-fluorobenzoic acid is an important intermediate in the synthesis of derivatives of indole, such as the potent and selective thromboxane/prostaglandin endoperoxide receptor antagonist L-670,596 or the anti-inflammatory agent Etodolac. Compounds of this type have therapeutic applications. 2-Amino-3-fluoro-benzoic add is aiso an important precursor for the synthesis of fluoroacridines, which can be converted to interesting tridentate ligands, such as Acriphos. ... 

Amino-3-fluorobenzoic acid Anthranilic acid, 3-fluoro- (8) Benzoic acid, 2-amino-3-fluoro-(10) (825-22-9)... 

A/-[4-[(4-[ F]Fluorobenzylidene)amino-oxy]butyl]maleimide ([ F]FBABM) was synthesised in two steps, involving the preparation of 4-[ F]fluorobenzaldehyde (see Section 4.3.1.1), in an overall radiochemical yield of 35% in 60 min [267], whereas A/-[2-(4-[ F]fluorobenzamido)ethyl]maleimide ([ F]FBEM) was synthesised in three steps via 4-[ F]fluorobenzoic acid (see Section 4.3.1.1) in an overall radiochemical yield of 12% in 150 min [268]. Finally, based on the successful use of nucleophilic /leferoaromatic ort/io-radiofluorination in the pyridine series (see Section 4.3.2.1), 1-[3-(2-p F]fluoropyridin-3-yloxy)propyl]pyrrole-2,5-dione was prepared in 17-20% non-decay-corrected radiochemical yield in a three-step pathway taking less than 110 min [13,269]. These three reagents have been successfully coupled to peptides and proteins (>80% radiochemical yield in 10 min). 

U. Sidelmann, S.H. Hansen, C. Gavaghan, A.W. Nicholls, H.A.J. Carless, J.C. Lindon, I.D. Wilson, J.K. Nicholson, Development of a simple liquid chromatographic method for the separation of mixtures of positional isomers and anom-ers of synthetic 2-, 3- and 4-fluorobenzoic acid glucuronides formed via acyl migration reactions, J. Chromatogr. B Biomed. Sci. Appl. 685 (1996) 113-122. 

Other benzoic acid derivatives (i.e., nitrobenzoic acids, chlorobenzoic acids, and fluorobenzoic acids) were analyzed using Zorbax-C8, Zorbax-Phenyl, and Zorbax-CN columns. A mobile phase of 75% 25 mM sodium citrate (pH 2.5) and 25% methanol was used for the Zorbax-C8 method, while 65% 25 mM sodium citrate and 35% methanol were used for the Zorbax-Phenyl and Zorbax-CN methods. Detection was performed on the basis of the UV absorbance at 290 nm. 

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