Process Intensification of Tetrazole reaction through tritylation of 5-[4 0 - (Methyl) Biphenyl-2-Yl] using microreactors Yadagiri Maralla a , Shirish Sonawane a, *, Dhurke Kashinath b , Makarand Pimplapure c , Banoth Paplal b a Department of Chemical Engineering, National Institute of Technology, Warangal, Telangana, India b Department of Chemistry, National Institute of Technology, Warangal, Telangana, India c Department of Application Development and Research and Development, Corning Reactor Technologies, Pune, Maharashtra State, India A R T I C L E I N F O Article history: Received 3 October 2016 Received in revised form 10 November 2016 Accepted 4 December 2016 Available online 14 December 2016 Keywords: Synthesis Tritylation Microreactors Biphenyl Tetrazole A B S T R A C T Currently, process intensification research is focused on use of the continuous micro reactor over the batch reactors. The micro reactor process gives continuous product output, effective micro mixing and better yield in small residence time over batch reactors. A continuous flow process has been successfully developed for the tritylation of 5-(4 0 -methyl-[1,1 0 -biphenyl]-2-yl)-1H-tetrazole [MBPT] using different microreactors. The reaction was carried out in three different configurations of microreactors. The SSCR– 1 mm and 2 mm (Stainless steel capillary coil micro reactors) gives yield of 93.72 and 92.87% for the residence time of 71 s and 324 s respectively. Among the three microreactors, Corning 1 AFR afforded effectively higher yield (95.18%) for the residence time of 27 s. Thus, 5-(4 0 -methyl-[1,1 0 -biphenyl]-2-yl)-1- trityl-1H-tetrazole, a useful intermediate material for some of the pharmaceutical products that can be produced industrially using microreactor. © 2016 Elsevier B.V. All rights reserved. 1. Introduction The triphenylmethyl (trityl) group is a common protecting group for hydroxyls benzyl tetrazole and biphenyl tetrazole. It can be easily substituted and detached by mild acid treatment [1–5]. It is widely accepted that the tritylation reaction preponderantly consists of an attack by the triphenylmethyl carbonium ion on the nucleophilic substrate via a S N 1/S N 2 mechanism. The rate of substitution depends upon the potentiality of its components to favor the heterolytic splitting of the Tr–X bond. Triphenylmethyl chlorides and bromides (X = Cl, Br) are used in presence of inorganic bases such as sodium carbonate and potassium carbonate or organic bases such as triethylamine, pyridine, N, N- dimethylaminopyridine (DMAP), 2,4,6-tertbutyl pyridine, 2,4,6- collidine or 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) etc. [6,7]. 5-(4 0 -methyl-[1,1 0 -biphenyl]-2-yl)-1-trityl-1H-tetrazole (MBPTT) structure shown in chemical structure 1.1 is a key intermediate used for the preparation of various angiotensin-II antagonists, which belongs to the sartan family drugs [8–12] such as losartan potassium, candesartan, trityl olmesartan, valsartan, trityl candesartan cilexetil, trityl Irbesartan etc. [13–17]. In recent studies, researchers are interested to convert batch processes to continuous flow processes to minimize the reaction time and production cost. The main advantages of the flow processes over the batch is continuous product output and effective micro mixing and better selectivity in small space time * Corresponding author. Tel.: +91 870 2462626. E-mail address: shirish@nitw.ac.in (S. Sonawane). http://dx.doi.org/10.1016/j.cep.2016.12.003 0255-2701/© 2016 Elsevier B.V. All rights reserved. Chemical Engineering and Processing 112 (2017) 9–17 Contents lists available at ScienceDirect Chemical Engineering and Processing: Process Intensification journal homepa ge: www.elsev ier.com/locate/cep