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Microfluidic synthesis of tert-butyl peresters via KI-catalyzed oxidative coupling of methyl arenes and tert-butyl hydroperoxide Jiawei Hua, Shiyu Guo, Zhao Yang, Zheng Fang, and Kai Guo Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.7b00248 • Publication Date (Web): 25 Aug 2017 Downloaded from http://pubs.acs.org on August 27, 2017
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Organic Process Research & Development
Microfluidic synthesis of tert-butyl peresters via KIcatalyzed oxidative coupling of methyl arenes and tert-butyl hydroperoxide Jiawei Hua, † Shiyu Guo, † Zhao Yang, ‡ Zheng Fang,*, † Kai Guo*,†,§ †
College of Biotechnology and Pharmaceutical Engineering Nanjing Tech University, 30 Puzhu
Rd S., Nanjing, 211816, China ‡
College of Engineering China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210003,
China §
State Key Laboratory of Materials-Oriented Chemical Engineering, 30 Puzhu Rd S., Nanjing,
211816, China Table of Contents graphic:
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ABSTRACT: A green and efficient organic–aqueous two phase reaction route for the synthesis of tert-butyl peresters by KI-catalyzed C-H oxidation of methyl arenes in a microfluidic chip reactor has been developed. Moreover, a series of tert-butyl peresters products were obtained in moderate to good yields under metal-free conditions. A scale-up continuous flow system was constructed to verify the application of this method.
KEYWORDS: Two phase reaction, tert-butyl peresters, Methyl arenes, Microfluidic chip reactor, Scale-up INTRODUCTION tert-butyl peresters, the common core organic compounds, play an important role in organic synthesis.1 Traditionally, tert-butyl peresters were obtained by utilizing carboxylic acid and its derivatives with TBHP (tert-butyl hydroperoxide).2 In 2011, Wan’s group reported a novel method for the synthesis of tert-butyl peresters from aldehydes which is distinguished by high atom economy and free of base (Scheme 1, eq.1).3 Wang’s group discovered a TBAI (tetrabutylammonium iodide)-catalyzed oxidation of alcohols to prepare tert-butyl peresters at room temperature in aqueous system.4 Transition metals are of significance in these transformations, which might provide a chance for formation of C-H, C-N, C-O bonds via crossdehydrogenative coupling (CDC) reactions.5 Recently, Niknam’s group developed a coppercatalyzed oxidative coupling of benzyl cyanides with TBHP to synthesize tert-butyl peresters under solvent-free conditions (Scheme 1, eq.2).6 However, these methods mentioned above still have some apparent drawbacks. It’s hard to enhance the mixing efficiency of the organic– aqueous two phase reactions in batch reactor. Although extending the reaction time might improve the yield, the quality and stability of the desired product could not be maintained.
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Organic Process Research & Development
Furthermore, safety risks existed in the conventional scale-up batch reaction for the synthesis of peresters. Microfluidic system, the emerging platform for chemical synthesis, has been developing rapidly in green chemistry.7 Compared to traditional chemical batch reactors, microfluidic reactors possess thinner channels with dimensions of tens to hundreds of micrometres,8 which could improve the efficiency of mass transfer and heat transfer between oil and water.9 Besides, the state of mixing could be controlled by regulating temperature and the average flow rate precisely.10 As a phase transfer catalyst, TBAI worked well in previous method for the synthesis of tert-butyl peresters. However, the cheaper KI could not be applicable to these reactions due to the poor efficiency of the organic–aqueous two phase reactions in conventional batch reactor. Traditional methods for the synthesis of tert-butyl peresters required several to twenty hours to react, while the microfluidic system merely consumed a little residence time and the product was constantly collected, which might efficiently solved the potential safety problem. Herein, we developed a novel organic–aqueous two phase route to tert-butyl peresters via KI-catalyzed oxidative coupling of methyl arenes and TBHP in a microfluidic chip reactor (Scheme 1, eq.3). Scheme 1. Microfluidic synthesis of tert-butyl peresters via KI-catalyzed oxidative coupling of methyl arenes and tert-butyl hydroperoxide
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RESULTS AND DISCUSSION Initially, a model reaction of toluene (1a) and TBHP (2) to form tert-butyl peresters (3a) in a microfluidic chip reactor was chosen as the model reaction to optimize reaction conditions by examining a series of reaction parameters. And the results were summarized in Table 1. As shown in Table 1, the microfluidic chip reactor is consisted of syringe pumps (A and B), Controller (C) and Start unit (D). The volume of syringe and chip are 1 mL and 10 µL, respectively. The reaction time can be modulated by adjusting the flow rate of syringes. What’ more, the heating device of the chip fixed on Start unit (D) was controlled by Controller (C). The use of microfluidic chip reactor provides a medium for our reaction, which is safe, efficient, environmental friendly and with practical application. Firstly, a series of phase transfer catalysts, such as TBAI (tetrabutylammonium iodide), TBAB (tetrabutylammonium bromide) and TBAC (tetrabutylammonium chloride) were screened to investigate the reaction conditions (Table 1, Table 1. Optimization of reaction conditionsa
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Organic Process Research & Development
Entry
Catalyst
T (℃)
Time (s)
Yield (%)b
1
TBAI
40
40
62
2
TBAB
40
40
