1-(1-Alkenyl)benzotriazoles: Novel α-Hydroxyacyl Anion Equivalents for the Synthesis of α-Hydroxy Ketones

α-Lithiated 1-(1-alkenyl)benzotriazoles, generated from the reactions of 1-(1-alkenyl)benzotriazoles with n-BuLi, react with a variety of electrophiles to afford α-substituted 1-(1-alkenyl)benzotriazoles which undergo epoxidation with m-CPBA followed by hydrolysis to give α-hydroxy ketones in good yields. Thus, 1-(1-alkenyl)benzotriazoles behave as α-hydroxyacyl anion equivalents.     

Benzyne click chemistry: synthesis of benzotriazoles from benzynes and azides

A variety of substituted benzotriazoles have been prepared by the [3 + 2] cycloaddition of azides to benzynes. The reaction scope is quite general, affording a rapid and easy entry to substituted, functionalized benzotriazoles under mild conditions.     

Synthesis and transformations of 1-(1,3-butadien-1-yl)benzotriazoles

1-[α-(Phenylthio)alkyl]benzotriazoles were converted into the corresponding 1-(1,3-butadien-1-yl)benzotriazoles in good yields by one-pot sequential reactions with (i) lithium diisopropylamide, (ii) allyl bromide or cinnamyl chloride, and (iii) potassium t-butoxide. Diels-Alder and hetero [4 + 2] cycloadditions of 1-(1,3-butadien-1-yl)benzotriazoles and some transformations of their α-lithio derivatives were studied.     

Benzotriazole-mediated syntheses of depsipeptides and oligoesters

Reactions of O-Pg(α-hydroxyacyl)benzotriazoles with (a) unprotected α-hydroxycarboxylic acids, (b) amino acids, and (c) amines afforded, respectively, chirally pure (a) oligoesters, (b) depsidipeptides, and (c) amide conjugates (yields 52-94%). N-Pg(α-Aminoacyl)benzotriazoles reacted with α-hydroxycarboxylic acids to yield depsidipeptides (47-87%). N-Pg(depsidipeptidoyl)benzotriazoles, obtained from depsidipeptides, gave depsitripeptides (yields 55-78%) on reaction with amino acids and α-hydroxycarboxylic acids. O-Acylation of α-hydroxycarboxylic acids with N-Pg(α-aminoacyl)benzotriazoles followed by deprotection produced unprotected depsides useful for the preparation of depsitripeptides.     

Copper‐Catalyzed Cascade Cyclization Reaction of 2‐Haloaryltriazenes and Sodium Azide: Selective Synthesis of 2 H‐Benzotriazoles in Water

A new approach to the synthesis of 2 H‐benzotriazoles is described. This strategy is based on the copper‐catalyzed C?N coupling of 2‐haloaryltriazenes or 2‐haloazo compounds with sodium azide and the intramolecular addition of nitrene to N?N bonds. This approach allows the synthesis of various N‐amino‐ and N‐aryl‐2 H‐benzotriazoles in water, in good to excellent yields. The procedure is simple and the starting materials and catalyst are easily available, offering a practical and convenient synthetic route to 2‐substituted benzotriazoles.     

Synthesis and Biological Activity Studies of Some Novel Mannich Bases of Benzotriazolyl Triazoles

A series of substituted phenyl methyl piperazine triazolyl benzotriazoles 4a , 4b , 4c , 4d , 4e , 4f , 4g have been synthesized through the Mannich reaction of substituted phenyl triazolyl benzotriazoles 3a , 3b , 3c , 3d , 3e , 3f , 3g . The substituted phenyl triazolyl benzotriazoles were prepared from benzotriazolyl acetohydrazide, where the cyclization was facilitated through ammonium acetate and aryl aldehydes. The IR, ¹H NMR, mass spectral data and elemental analysis were performed to assign the structure. All the newly synthesized compounds were screened for their antimicrobial and antioxidant activity.     

Synthesis and Structure of 1- and 2-Isomers of (Trimethoxysilylmethyl) and (Silatranylmethyl)benzotriazole

We have synthesized 1- and 2-(trimethylsilylmethyl)- and 1- and 2-(trimethoxysilylmethyl)benzotriazoles by reaction of 1,2,3-benzotriazolylsodium with trimethyl- or trimethoxy(chloromethyl)silane. We obtained 1- and 2-(silatranylmethyl)benzotriazoles by transesterification of the latter with triethanolamine.     

N-1-取代苯并三唑的简易快速合成及生物活性

本文应用相转移催化和微波辐射合成１０个Ｎ－１－取代苯并三唑;Ｎ－１－苄基、－乙氧羰基亚甲基、－芳基、－乙酰基、２个一羧亚甲氧烷基苯并三唑及４个二（苯并三唑基）烷烃,其中有７个为新化合物,这种简易快速方法具有产率高、反应时间短、操作方便、低能耗和无环境污染的优点。初步测试它们的生物活性,大多数化合物具有较好的抗菌活性。     

Synthesis of new 1,2,3-triazolo[1,2-a]benzotriazoles or 2,3-benzo-1,3a,6,6a-tetraazapentalenes

Some new v-triazolo[1,2-a]benzotriazoles or 2,3-benzo-1,3a,6,6a-tetraazapentalenes were prepared according to previously employed synthetic routes concerning deoxycyclization reactions of appropriate nitrophenyl-1,2,3-triazole derivatives and/or thermal decompositions of appropriate azidophenyl-1,2,3-triazoles. The nitration of 9-phenyl-1,2,3-triazolo[1,2-a]benzotriazoles allowed the isolation of some mononitro- and trinitro-derivatives, whose structures were assigned by chemical and spectroscopic methods.     

DBU-catalyzed transprotection of N-Fmoc-cysteine di- and tripeptides into S-Fm-cysteine di- and tripeptides

The transprotection of N-Fmoc-cysteine containing di- and tripeptides possessing a free SH group to produce the corresponding S-Fm-cysteine di- and tripeptides bearing a free amino group is accomplished efficiently with DBU in dry THF. The N-Fmoc to S-Fm transformation mechanism is discussed. S-Fm-Cysteine di- and tripeptides readily form amide bonds on coupling with N-(Pg-α-aminoacyl)benzotriazoles and N-(Pg-α-dipeptidoyl)benzotriazoles to give larger peptides.     

Renaissance of Ring‐Opening Chemistry of Benzotriazoles: New Wine in an Old Bottle

1,2,3‐Benzotriazoles could undergo ring cleavage to form ortho‐amino arenediazonium or α‐diazo‐imine species via a Dimroth‐type equilibrium. Historically, the synthetic potential of this unique reactivity had remained underdeveloped. Recently, some new strategies have been developed to effect the ring‐opening chemistry of benzotriazoles in more practical manners. A wide range of conceptually novel and synthetically useful reactions have been developed, which enable the access to diverse valuable heterocycles and ortho‐amino arene derivatives. As one of the players in this field, our group has also contributed a series of intriguing transition‐metal‐catalyzed denitrogenative functionalizations of benzotriazoles. In this account, we aim to provide an overview of the ring‐opening chemistry of benzotriazoles, with a focus on relevant works published in the past decade. In order to show a whole picture of the research field, some pioneering works in its developing history will also be discussed briefly.     

Pd/PC‐Phos‐Catalyzed Enantioselective Intermolecular Denitrogenative Cyclization of Benzotriazoles with Allenes and N‐Allenamides

Reported herein is an asymmetric Pd/PC‐Phos‐catalyzed denitrogenative cyclization of benzotriazoles with allenes and N‐allenamides, representing the first example of enantioselective denitrogenative cyclizations of benzotriazoles. A series of optically active 3‐methyleneindolines were obtained in good yields with high ee values. The use of inexpensive and readily available starting materials, high regio‐ and enantioselectivity, a broad substrate scope, mild reaction conditions, no need for base, as well as versatile functionalization of the 3‐methyleneindolines make this approach attractive.     

Product analyses of ozone mediated nitration of benzimidazole derivatives with nitrogen dioxide: formation of 1-nitrobenzimidazoles and conversion to benzotriazoles

Several benzimidazole derivatives having electron-withdrawing or -donating substituent(s) at the benzene moiety were used as models of the imidazole moiety of purine bases and their nitration with nitrogen dioxide and ozone (so-called Kyodai nitration) were examined. Products were extracted from the reaction mixture with AcOEt and their structures were analyzed. 1-Nitrobenzimidazole derivatives and unexpected 1-nitrobenzotriazole derivatives were identified. Although the yields of 1-nitrobenzimidazole derivatives were quite low, these were all new compounds that could be obtained only by Kyodai nitration. It was speculated that benzotriazoles were formed via 1-nitrobenzimidazoles and subsequent nitration toward benzotriazoles resulted in the formation of 1-nitrobenzotriazoles.     

Organic Reactions in Ionic Liquids： Ionic Liquid-promoted Three-component Condensation of Benzotriazole with Aldehyde and Alcohol

1-(α-Alkoxyalkyl)benzotriazoles are readily synthesized from three-component condensation of benzotriazole with aldehyde and alcohol in ionic liquid [Bmim]PF6.     

beta-acylvinyl anion and dianion equivalents: lithiation of 1-[(2EZ)-3-chloroprop-2-enyl]-1H-1,2,3-benzotriazole: preparation and elaboration of 1-(2-oxiranylvinyl)-1H-benzotriazoles

The allyllithium generated from 1-[(2EZ)-3-chloroprop-2-enyl]-1H-1,2,3-benzotriazole (5) and LDA, in the presence of HMPA, reacts with enolizable and nonenolizable carbonyls solely at the CCl terminus to give 1-(2-oxiranylvinyl)benzotriazoles 6a-g in 61-82% yields. Allyllithiums generated from 6a,c reacted exclusively at the CBt terminus to give 10a-d in 68-88% yields. Acidic hydrolysis of (oxiranylvinyl)benzotriazoles 6a-g and 10a-d provided 4-hydroxyalk-2-en-1-one derivatives 12a,b,c,e,g, 13a-d, and furan 14 in 54-86% yields.     

Synthesis of Heterocycles through Denitrogenative Cyclization of Triazoles and Benzotriazoles

During the past few decades, there has been considerable growth in the development of denitrogenative reactions of triazole skeletons to construct valuable cyclic compounds, particularly heterocycles. Despite the inherent difficulty of the ring-opening of triazole derivatives, many novel and efficient approaches have arisen in this area mainly with the use of transition metal (such as rhodium, palladium, silver, copper) catalysis, photolysis, or free radical mediated reactions. Generally, these procedures begin with the ring-opening of 1,2,3-triazoles or benzotriazoles followed by N₂ extrusion and subsequent diverse transformations, which enable the rapid synthesis of various heterocycles in a single step. To avoid overlap with other related reviews, this minireview covers the recent advances in the denitrogenative cyclization of 1,2,3-triazoles since 2016 and the denitrogenative cyclization of benzotriazoles since 2012.     

Aryne click chemistry: synthesis of oxadisilole fused benzotriazoles or naphthotriazoles from arynes and azides

The oxadisilole fused benzotriazoles or naphthotriazole derivatives have been synthesized by 1,3-dipolar cycloaddition of various azides with arynes generated in situ from benzobisoxadisilole or 2,3-naphthoxadisilole in good yields under mild conditions.     

A facile synthesis of 3-substituted-2-aminothiophenes and 1,3-disubstituted-2-methylthiopyrroles

Electron-rich 3-functionalized-2-aminothiophenes 6 and 1,3-disubstituted-2-methylthiopyrroles 10 were synthesized from substituted allyl benzotriazoles 2 and isothiocyanates 3 via condensation and subsequent heterocyclization.     

N-alkylation of benzimidazoles and benzotriazole via phase transfer catalysis

N-methyl and other N-alkyl benzimidazoles and benzotriazoles were prepared by 18-crown-6 catalysis involving basic aqueous solutions of the heterocycles and organic solutions of alkyl iodides or bromides.     

Microwave-assisted benzyne-click chemistry: preparation of 1H-benzo[d][1,2,3]triazoles

The benzotriazoles were prepared by three-component and two-component microwave-assisted [3+2] cycloadditions of various azides to benzyne, 3-methoxybenzyne, and 4,5-difluorobenzyne. In the three-component reaction, the aryne is generated, in the presence of an azide prepared in situ, by the reaction of an o-(trimethylsilylaryl) triflate with either CsF or KF/18-Crown-6. However, in the two-component reactions, a freshly prepared azide is added to the reaction vessel prior to aryne generation. Good to excellent yields of benzotriazoles were obtained in 15-20 min when the microwave-assisted reactions were carried out at 125 °C. These reaction times are significantly faster than similar reactions carried out using conventional heating.