Chehade K A, Spielmann H P
Departments of Biochemistry and Chemistry and The Kentucky Center for Structural Biology, University of Kentucky, Lexington, Kentucky 40536-0084, USA.
J Org Chem. 2000 Aug 11;65(16):4949-53. doi: 10.1021/jo000402p.
p-Azidotetrafluoroaniline (1) was synthesized in 65-73% yield by two different methods employing a stable carbamate intermediate. The first method trapped the intermediate isocyanate generated via a modified Curtius rearrangement with 2-methyl-2-propanol or 2-(trimethylsilyl)ethanol to form the stable carbamates 2d and 2e, respectively. Benzoic acid 2c was first converted to its acid chloride with PCl(5). Displacement of the chloride by NaN(3) in acetone/water formed the acyl azide. Thermal rearrangement followed by the addition of the appropriate alcohols provided the carbamates. The acid labile carbamate 2d was deprotected with HCl/AcOH to provide 1, while trifluoroacetic acid was required to deprotect 2e and afford 1. In the second path, 1 was synthesized in five steps from pentafluoronitrobenzene (3a) in 65% overall yield. Compound 3a was converted into 4-azidotetrafluoronitrobenzene (3b) with NaN(3) in 93% yield and was used without further purification to form 1, 4-diaminotetrafluorobenzene (3c) by Sn/HCl reduction in 85% yield. The mono-9-fluorenylmethoxycarbonyl (FMOC) derivative 3d was formed from 3c with FMOC-Cl and pyridine in EtOAc in 92% yield. Diazotization of 3d under anhydrous conditions with TFA/NaNO(2) and NaN(3) gave 3e in 87% yield. The aryl azide 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 cyclohexylamine 11, diamine 3c, and azobenzene 12 as the primary products. The formation 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.
对叠氮基四氟苯胺（1）通过两种不同方法合成，产率为65 - 73%，采用稳定的氨基甲酸酯中间体。第一种方法是利用2 - 甲基 - 2 - 丙醇或2 - （三甲基甲硅烷基）乙醇捕获经由改进的库尔提斯重排生成的异氰酸酯中间体，分别形成稳定的氨基甲酸酯2d和2e。苯甲酸2c首先用PCl₅转化为其酰氯。在丙酮/水中用NaN₃取代氯原子形成酰基叠氮。热重排后加入适当的醇得到氨基甲酸酯。酸不稳定的氨基甲酸酯2d用HCl/AcOH脱保护得到1，而脱保护2e并得到1则需要三氟乙酸。在第二条路线中，由五氟硝基苯（3a）经五步合成1，总产率为65%。化合物3a用NaN₃转化为4 - 叠氮基四氟硝基苯（3b），产率为93%，无需进一步纯化即用于通过Sn/HCl还原以85%的产率形成1，4 - 二氨基四氟苯（3c）。3c与芴甲氧羰基氯（FMOC - Cl）和吡啶在乙酸乙酯中反应形成单 - 9 - 芴甲氧羰基（FMOC）衍生物3d，产率为92%。在无水条件下用TFA/NaNO₂和NaN₃对3d进行重氮化反应，产率为87%得到3e。在芴基体系的2 - 位同时硝化形成芳基叠氮。用哌啶除去保护基，产率为93%得到1。在环己烷中用254 nm光照射1，得到环己胺11、二胺3c和偶氮苯12作为主要产物。C - H插入产物11的形成表明1在光解时形成单线态氮烯。制备了两种异双功能光亲和试剂碘乙酰胺9和丹磺酰衍生物10。
