4760-34-3Relevant articles and documents
Regioselective Radical Arene Amination for the Concise Synthesis ofortho-Phenylenediamines
Gillespie, James E.,Morrill, Charlotte,Phipps, Robert J.
supporting information, p. 9355 - 9360 (2021/07/19)
The formation of arene C-N bonds directly from C-H bonds is of great importance and there has been rapid recent development of methods for achieving this through radical mechanisms, often involving reactiveN-centered radicals. A major challenge associated with these advances is that of regiocontrol, with mixtures of regioisomeric products obtained in most protocols, limiting broader utility. We have designed a system that utilizes attractive noncovalent interactions between an anionic substrate and an incoming radical cation in order to guide the latter to the areneorthoposition. The anionic substrate takes the form of a sulfamate-protected aniline and telescoped cleavage of the sulfamate group after amination leads directly toortho-phenylenediamines, key building blocks for a range of medicinally relevant diazoles. Our method can deliver both free amines and monoalkyl amines allowing access to unsymmetrical, selectively monoalkylated benzimidazoles and benzotriazoles. As well as providing concise access to valuableortho-phenylenediamines, this work demonstrates the potential for utilizing noncovalent interactions to control positional selectivity in radical reactions.
Ru-Catalyzed Selective Catalytic Methylation and Methylenation Reaction Employing Methanol as the C1 Source
Biswas, Nandita,Srimani, Dipankar
, p. 10544 - 10554 (2021/07/31)
Methanol can be employed as a green and sustainable methylating agent to form C-C and C-N bonds via borrowing hydrogen (BH) methodology. Herein we explored the activity of the acridine-derived SNS-Ru pincer for the activation of methanol to apply it as a C1 building block in different reactions. Our catalytic system shows great success toward the β-C(sp3)-methylation reaction of 2-phenylethanols to provide good to excellent yields of the methylated products. We investigated the mechanistic details, kinetic progress, and temperature-dependent product distribution, which revealed the slow and steady generation of in situ formed aldehyde, is the key factor to get the higher yield of the β-methylated product. To establish the environmental benefit of this reaction, green chemistry metrics are calculated. Furthermore, dimerization of 2-naphthol via methylene linkage and formation of N-methylation of amine are also described in this study, which offers a wide range of substrate scope with a good to excellent yield.
2-aminobenzimidazoles for leishmaniasis: From initial hit discovery to in vivo profiling
Ferreira, Rafael Augusto Alves,Junior, Celso de Oliveira Rezende,Martinez, Pablo David Grigol,Koovits, Paul John,Soares, Bruna Miranda,Ferreira, Leonardo L. G.,Michelan-Duarte, Simone,Chelucci, Rafael Consolin,Andricopulo, Adriano D.,Galuppo, Mariana K.,Uliana, Silvia R. B.,Matheeussen, An,Caljon, Guy,Maes, Louis,Campbell, Simon,Kratz, Jadel M.,Mowbray, Charles E.,Dias, Luiz Carlos
, (2021/03/24)
Leishmaniasis is a major infectious disease with hundreds of thousands of new cases and over 20,000 deaths each year. The current drugs to treat this life-threatening infection have several drawbacks such as toxicity and long treatment regimens. A library of 1.8 million compounds, from which the hits reported here are publicly available, was screened against Leishmania infantum as part of an optimization program; a compound was found with a 2-aminobenzimidazole functionality presenting moderate potency, low metabolic stability and high lipophilicity. Several rounds of synthesis were performed to incorporate chemical groups capable of reducing lipophilicity and clearance, leading to the identification of compounds that are active against different parasite strains and have improved in vitro proper-ties. As a result of this optimization program, a group of compounds was further tested in anticipation of in vivo evaluation. In vivo tests were carried out with compounds 29 (L. infantum IC50: 4.1 μM) and 39 (L. infantum IC50: 0.5 μM) in an acute L. infantum VL mouse model, which showed problems of poor exposure and lack of efficacy, despite the good in vitro potency.