Green chem.: Cui Xiuling and PI Chao's team reported the synthesis of 1,2,3-benzotriazine by n-center [1,2] rearrangement of 3-aminoindazole catalyzed by iodine

1,2,3-benzotriazine and its derivatives are important nitrogen-containing heterocyclic compounds, which are widely used in organic synthesis due to their unique chemical properties and biological activities In particular, 4-substituted 1,2,3-benzotriazine is widely found in some bioactive molecules, such as anti-tumor and anti-inflammatory molecules and vascular endothelial growth factor inhibitors However, there are some problems in the past synthesis methods, such as complicated steps and harsh conditions, so it is of great significance to develop a simple and effective method for the construction of 1,2,3-benzotriazine skeleton Recently, Cui Xiuling and PI Chao's team from Zhengzhou University reported the rearrangement of n-center [1,2] of aniline with 3-aminoindazol catalyzed by iodine under simple reaction conditions, and synthesized a variety of n-phenyl-1,2,3-benzotriazine-4 (3H) - imine derivatives (scheme 1) Relevant research results were published in green chem (DOI: 10.1039/c9gc03567b) (source: Green chem.) at first, the author used aniline (1a) and 3-aminoindazole (2a) as model substrates to optimize the reaction conditions (Table 1) It is gratifying that under the action of I 2 and H 2O 2, the substrate reacts in methanol at 80 ℃ for 12 hours, and the target product 3AA is obtained in 20% yield Then through the selection of oxidants, additives, solvents and other conditions, the author found that the target product 3AA can be obtained in 86% yield by using I 2 as catalyst, TBHP as oxidant, TBAI as additive, aniline and 3-aminoindazole in 1-propanol at 80 ℃ for 12 hours (source: Green chem.) after determining the best reaction conditions, the author first investigated the universality of aniline substrate (scheme 2) The corresponding products (3AA - 3ia, 3ra - 3ta) can be obtained from aniline with various halogen and electron donor groups Benzylamine and 4-aminobiphenyl (3ua-3va) are also compatible in this system In addition, secondary amines were also suitable substrates, and the target product (3wa - 3xa) was obtained in 63-72% yield (source: Green chem.) then, the author investigated the application scope of 3-aminoindazole (scheme 3) When the C-4 position of 3-aminoindazole is linked with halogen, methyl or methoxy group, the target product (3ab-3ae) can be obtained in 47-91% yield The introduction of substituents at C-5 and 6 sites of the substrate was also compatible with the reaction conditions, and the target product (3af - 3aE) was obtained in good yield However, the catalytic system is not suitable for 5-nitro-1h-indole-3-amine, which may be due to its low electron cloud density (3 ah) (source: Green chem.) in order to understand the mechanism of the reaction, the author conducted a series of control experiments When tempo was added to the reaction system, the target product could be obtained in 68% yield, which indicated that the free radical process (scheme 5a) might not be involved in the reaction The results of other control experiments show that the iodine ion of TBAI is not the initial step of the reaction, but plays the role of phase transfer catalyst (scheme 5b) The results of conditions C and d show that I 2 and oxidant are very important for the initial step of the reaction (source: Green chem.) based on the above experimental results and previous reports, the author proposed a reasonable mechanism for this reaction (scheme 6) Firstly, n-iodoaminoindazole A and hi were formed by iodization of 2A under the action of TBHP Then, intermediate a generates intermediate B through intramolecular nucleophilic reaction, and then electron rich 1A nucleophilic attack B generates intermediate C Then, the intermediate C was cleaved to d by intramolecular C-N bond Finally, the oxidant oxidizes d to the desired product 3AA In addition, TBHP oxidizes hi to regenerate I 2 with catalytic amount (source: Green chem.) Summary: the author has successfully developed a novel direct iodine catalyzed n-center [1,2] rearrangement of 3-aminoindazole with aniline Under simple reaction conditions, various 1,2,3-benzotriazines can be easily obtained in medium to excellent yield, and have good functional group tolerance It is worth noting that the formation of C-N bond and N-N bond is simultaneous, and I2 is a cheap catalyst for in-situ formation of n-haloamines.