A facile method for the activation of hydroxy-substituted carboxylic acids using benzotriazole chemistry without prior protection of the hydroxy substituents is presented. The N-acylbenzotriazole intermediates 2a-g, 6a-d, and 9a-c have been used for high-yielding synthesis of both aliphatic (3a-l) and aromatic (7a-h, 10a-f) hydroxy carboxamides. High yields of aromatic hydroxy esters 12a-h and 13a-i were obtained using either neat alcohols in neutral microwave conditions or nucleophilic alkoxides and the intermediate N-(arylacyl)benzotriazoles. Moderate yields were obtained in the case of aliphatic hydroxy esters 11a,b and thiolesters 11e-g from the intermediates 2a-c.
Reactions of benzotriazol-1-yl(1H-pyrrol-2-yl)methanone 10 and benzotriazol-1-yl(1H-indol-2-yl)methanone 11 with diverse ketones, isocyanates, and isothiocyanates in the presence of base afforded pyrrolo[1,2-c]oxazol-1-ones 1, oxazolo[3,4-a]indol-1-ones 2, pyrrolo[1,2-c]imidazoles 3, and imidazo[1,5-a]indoles 4 by a simple one-step procedure.
Submitted to honor the 85th birthday of Rolf Huisgen: inspiring chemist and good friend An operationally straightforward and efficient benzotriazole-based method for the guanylation of diverse amines by use of the new reagent classes (bis-benzotriazol-1-yl-methylene)amines 13a ± 13f and benzotriazole-1-carboxamidines 17a ± 17i is described. The preparation is described for a variety of both acyclic and cyclic 1,2,3-trisubstituted guanidines in high yields.Introduction. ± A wide variety of structurally diverse molecules that incorporate guanidine units have been isolated from many microorganisms and higher plants [1]. Guanidines are core features of many therapeutically active compounds [2 ± 7], and guanidine alkaloids exhibit antiviral, antifungal, and antitumor activities [1]. Thus, procedures for the preparation of guanidines [8] are of great interest in medicinal chemistry, and much effort has been directed towards efficient syntheses of these compounds (see, e.g., [9]).The synthesis of guanidines 3 is complicated by their high basicity and nucleophilicity. Many syntheses utilize intermediates with easily removed protective groups. Common methods for the preparation of guanidines 3 involve attack of an amine 1 on various activated guanidinylating reagents 2a ± 2j (Scheme 1). Primary amines react smoothly and efficiently with these reagents, whereas sterically more demanding secondary or electronically deactivated aromatic amines face various difficulties.Methods for the preparation of guanidines 3 (Scheme 1) include: i) reaction of various ureas 2a with phosgene then treating the resultant Vilsmeier salt with amines 1 [10]; ii) using triflicguanidines 2b as guanidinylating reagents [11], or iii) guanylpyrazole 2c as guanidinylating reagents [12]. Several common routes to 3 involve the treatment of amines with electrophilic species 2d ± 2i generated from thioureas: iv) sulfonic acids 2d derived from N-alkyl-substituted thioureas
Novel mono- and symmetrical di-N-hydroxy- and N-aminoguanidines were readily prepared from the reaction of diverse hydroxylamines or hydrazines with reagent classes di(benzotriazol-1-yl)methanimine 6, (bis-benzotriazol-1-yl-methylene)amines 8a,b, benzotriazole-1-carboxamidines 10a-i, benzotriazole-1-carboximidamides 11a,b, and N'-hydroxy-1H-1,2,3-benzotriazole-1-carboximidamide 18. The preparation is described for a variety of N-hydroxy- and N-aminoguanidines with different substitution patterns in good yields.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.