Facile and efficient synthesis of 4-azidotetrafluoroaniline: A new photoaffinity reagent

p-Azidotetrafluoroaniline (1) was synthesized in 65-73% yield by two differ ent methods employing a stable carbamate intermediate. The first method tra pped the intermediate isocyanate generated via a modified Curtius rearrange ment with 2-methyl-2-propanol or 2-(trimethylsilyl)ethanol to form the stab le carbamates 2d and 2e, respectively. Benzoic acid 2e was first converted to its acid chloride with PCl5. Displacement of the chloride by NaN3 in ace tone/water formed the acyl azide. Thermal rearrangement followed by the add ition of the appropriate alcohols provided the carbamates. The acid labile carbamate 2d was deprotected with HCl/AcOH to provide 1, while trifluoroace tic acid was required to deprotect 2e and afford 1. In the second path, 1 w as synthesized in five steps from pentafluoronitrobenzene (3a) in 65% overa ll yield. Compound 3a was converted into 4-azidotetrafluoronitrobenzene (3b ) with NaN3 in 93% yield and was used without further purification to form 1,4-diaminotetrafluorobenzene (3c) by Sn/HCl reduction in 85% yield. The mo no-9-fluorenyl-methoxycarbonyl (FMOC) derivative Sd was formed from 3c with FMOC-Cl and pyridine in EtOAc in 92% yield. Diazotization of 3d under anhy drous conditions with TFA/NaNO2 and NaN3 gave 3e in 87% yield. The aryl azi de was formed with concurrent nitration of the 2-position of the fluorenyl system. The protecting group was removed with piperidine to afford 1 in 93% yield. Irradiation of 1 with 254 nm light in cyclohexane gave cyclohexylam ine 11, diamine 3c, and azobenzene 12 as the primary products. The formatio n of C-H insertion product 11 indicates that 1 forms a singlet nitrene upon photolysis. Two heterobifunctional photoaffinity reagents iodoacetamide 9 and dansyl derivative 10 were prepared.