Influence of temperature for the azide displacement in benzodiazepine derivatives: Experimental and DFT study of competing SN1, SN2 and double SN2 reaction pathways

TETRAHEDRON LETTERS

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Article

Santos Evangelista, Tereza Cristina¹  Delarmelina, Maicon^2,3  Addla, Dinesh¹  Allao, Rafael A.⁴  Kaiser, Carlos Roland¹  Carneiro, Jose Walkimar de M.²  Silva-Jr, Floriano Paes⁵  Ferreira, Sabrina Baptista¹ 

[1] Univ Fed Rio de Janeiro, Inst Quim, LaSOPB Lab Sintese Organ & Prospeccao Biol, BR-21941909 Rio De Janeiro, RJ, Brazil

[2] Univ Fed Fluminense, Inst Quim, BR-24020141 Niteroi, RJ, Brazil

[3] Cardiff Univ, Sch Chem, Main Bldg,Pk Pl, Cardiff CF10 3AT, Wales

[4] Univ Fed Rio de Janeiro, Inst Quim, BR-21941909 Rio De Janeiro, RJ, Brazil

[5] Fundacao Oswaldo Cruz, LaBECFar Lab Bioquim Expt & Computac Farmacos, Inst Oswaldo Cruz, BR-21040360 Rio De Janeiro, RJ, Brazil

关键词: Azide;    Pyrrolobenzodiazepines;    Nucleophilic substitution reactions;    Diastereoisomers;    Temperature;    DFT;   

DOI  :  10.1016/j.tetlet.2021.152937

来源: Elsevier

【 摘 要 】

Molecules carrying the azido functionality are widely used as intermediates in medicinal chemistry. Pyrrolobenzodiazepines are molecules with a broad range of interesting pharmacological properties. Due to the wide importance of azido-PBD as a key intermediate in many synthetic pathways, in this work we have investigated the effect of a variety of experimental parameters on the mechanism of nucleophilic substitution reaction for introducing an azide group into the PBD scaffold. This study was carried out by combined experimental and DFT approaches, showing that S(N)2 and double S(N)2 pathways are possible and highly dependent on the reaction temperature. (C) 2021 Elsevier Ltd. All rights reserved.

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