Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines

Abstract

The Pd-catalyzed N-arylation method for the synthesis of eighteen N,1-diaryl-1H-tetrazol-5-amine derivatives is reported. By running the reactions at 35 ºC, compounds were isolated as single isomers since the undesired Dimroth rearrangement was completely suppressed. Furthermore, the Dimroth rearrangement of N,1-diaryl-1H-tetrazol-5-amines was rationalized by conducting comprehensive experiments and NMR analysis as well as DFT calculations of thermodynamic stability of the compounds. It was established that the Dimroth rearrangement is thermodynamically controlled and the equilibrium of the reaction is determined by the stability of the corresponding isomers. The mechanism was investigated by additional DFT calculations and the opening of the tetrazole ring was shown to be the rate-determining step. By maneuvering Pd-catalyzed N-arylation and the subsequent Dimroth rearrangement two more N,1-diaryl-1H-tetrazol-5-amine derivatives were acquired, that otherwise cannot be synthesized by employing the C-N cross-coupling reaction.

N-Iodosuccinimide-Promoted [3 + 2] Annulation Reaction of Aryldiazonium Salts with Guanidines To Construct Aminotetrazoles

“…N -Acylation of 3a with aromatic carboxylic acid under basic conditions led to the herbicide-like molecular 4 in 72% yield (Scheme a) Scheme b) . Treating aminotetrazole 3g with tert -butyl nitrite under thermal conditions could give access to the deamination product 6 (Scheme c).…”

“…11 N-Arylation of 3g was conducted under palladium-catalyzed Buchwald−Hartwig conditions to deliver the secondary tetrazolyl amine 5 in 85% yield (Scheme 3b). 12 Treating aminotetrazole 3g with tert-butyl nitrite under thermal conditions could give access to the deamination product 6 (Scheme 3c). This masked strategy has been further applied in the preparation of drug-like intermediate 9, in which the NIS-promoted [3 + 2] annulation of diazonium salt 7 with guanidine 2a to form aminotetrazole 8 serves as a key step (Scheme 3d).…”

NIodosuccinimide-Promoted [3 + 2] Annulation Reaction of Aryldiazonium Salts with Guanidines To Construct Aminotetrazoles

“…: 178 -179 °C; This procedure is performed based on the reported literature. 3 A thick-walled, screw-capped glass tube was charged with a mixture of aryl bromide (16 mg, 0.1 mmol), 2-(4-Methoxyphenyl)-2H-tetrazol-5-amine 3g (23 mg, 0.12 mmol, 1.2 equiv), NaO t Bu 18 (16 mg, 0.14 mmol), Pd2(dba)3 (27 mg, 0.03 mmol), BINAP (44 mg, 0.07 mmol) and toluene (2 mL) and purged with argon. The tube was sealed, and the contents was heated at 110 o C in oil bath for 16 h. After the reaction was completed, the mixture was cooled to room temperature.…”