4-Fluoro-3-nitrophenyl azide

In the course of studies directed towards the development of photoaffinity labels for monoamine oxidase (MAO) isozymes, Shih and colleagues found that 4-fluoro-3-nitrophenyl azide (FNPA) (16) exhibited some interesting properties as an inhibitor of this enzyme [80]. MAO catalyzes the oxidative... 

To synthesize 4-fluoro-3-nitrophenyl azide (XXIV, 6.1.2) (Fleet et al. 1969), 4-fluoro-3-nitroaniline was diazotized in the usual manner and subsequently treated with sodium azide at -20°C to give a 70% yield of XXIV (m.p. 52°C) as light-sensitive straw colored needles which could be recrystallized from petroleum ether. 

The successful synthesis of these compounds showed the feasibility of using the carbodiimidazole coupling reaction in the formation of aryl-azido ATP analogs. For the general synthesis of the arylazidocarboxylic acids, 4-fluoro-3-nitroaniline is first diazotized in a concentrated hydrochloric acid medium in the presence of sodium nitrite [Eq. (2)]. The diazonium salt is subsequently treated with sodium azide, which results in the formation of a light-sensitive 4-fluoro-3-nitrophenyl azide (IV) [Eq. (3) ]. The structure of (IV) has been confirmed by its melting point of 52°-52.5° (recrystallized from petroleum ether) its NMR spectrum, 7.47 ppm (2 protons), 7.78 ppm (1 proton) and its mass spectrum, m/e 182. 

To 5.4 ml of an aqueous solution of )8-alanine (534 mg, 6 mmoles) and sodium carbonate (1.08 g, 10 mmole) is added 4-fluoro-3-nitrophenyl azide (900 mg, 4.9 mmoles). Ethanol (6.75 ml), water (5.4 ml), and another portion of ethanol (13.5 ml) are added subsequently to enhance the homogeneity of the reaction mixture. The reaction mixture suspension is stirred at 52° overnight with an attached cooling condenser. The resulting dark red mixture is first concentrated under reduced pressure to about one-third of its volume and then diluted with 18 ml of water. Two extractions with 45 ml of ether remove all the excess starting azide. The aqueous layer is acidified with 3 N HCl to pH 2 and extracted with three 90-ml portions of ether. The combined ether extract is washed three times, each with 50 ml of saturated NaCl solution, and is dried over sodium sulfate and then evaporated to dryness. The residue is recrystallized from hot ethanol. Yield 736 mg (59%) m.p. 142.5°-145° MS m/e 251 UV 260 (molar extinction coefficient 27.2 X... 

Fluoro-2 -deoxyuridylate-5,10-methyl-enetetrahydrofolate-thymidylate synthetase complex, 309 synthesis of, 311, 312 Fluorodinitrobenzene, 64, 65 Fluoroketones, 131 4-Fluoro-3-nitroaniline, 264 4-Fluoro-3-nitrophenyl azide, 264, 266, 267, 269... 

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