Special Issue Honoring Masahiro Murakami’s Contributions to Science
Aminotetrazole Synthesis from Secondary Amides by C–C Bond Nitrogenation
Cheng Zhang
a
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191, P. R. of China
,
Jianzhong Liu
a
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191, P. R. of China
a
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191, P. R. of China
,
Junhua Li
a
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191, P. R. of China
,
Song Song
a
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191, P. R. of China
a
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191, P. R. of China
b
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, East China Normal University, Shanghai 200062, P. R. of China
› Author AffiliationsWe thank the National Key R&D Program of China (No. 2021YFA1501700), the NSFC (Nos. 22293014, 22131002, 21901012), and the Tencent Foundation for financial support.
The development of novel methods for the preparation of aminotetrazoles is of long-standing interest to chemists due to the great importance of these compounds in chemistry and biology. Here, we report an efficient method for the preparation of aminotetrazoles from secondary amides by selective C–C bond cleavage. Compared with the conventional laborious and cumbersome approaches to aminotetrazoles, this chemistry provides a highly efficient nitrogenation strategy, with the installation of four nitrogen atoms into a secondary amide in one step.
17Aminotetrazoles 2a–y; General ProcedureUnder air, the appropriate secondary amide 1 (0.3 mmol) was dissolved in TCE (1 mL, 0.3 M) and Tf2O (169 mg, 0.6 mmol) was added at 0 °C. The mixture was stirred at 0 °C for 15 min, then TMSN3 (104 mg, 0.9 mmol) was added and the mixture was warmed to 40 °C. The vial was sealed, and the mixture was stirred under air at 40 °C for 24 h then cooled to RT. The reaction was quenched with Et3N (5 mL) at 0 °C, and the mixture was diluted with EtOAc (12 mL). The organic phase was filtered through a pad of silica gel using EtOAc to dilute the product. The filtrate was concentrated and the residue was purified by flash chromatography (silica gel).N-Methyl-1-phenyl-1H-tetrazol-5-amine (2a)Yellow solid; yield: 33.6 mg (64%). 1H NMR (400 MHz, CDCl3): δ = 7.53–7.47 (m, 2 H), 7.47–7.40 (m, 3 H), 4.86 (br s, 1 H), 3.06 (d, J = 4.8 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 155.29, 133.05, 130.06, 129.62, 123.80, 30.70. HRMS (ESI): m/z [M + H]+ calcd for C8H10N5: 176.0931; found: 176.0935
