Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with <em>p</em>-Nitrobenzoic Acid

Abstract

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and cost savings through the "scaling out" strategy as opposed to the traditional "scaling up". Herein, we report the reaction of diphenyldiazomethane with p-nitrobenzoic acid in both batch and flow modes. To effectively transfer the reaction from batch to flow mode, it is essential to first conduct the reaction in batch. As a consequence, the reaction of diphenyldiazomethane was first studied in batch as a function of temperature, reaction time, and concentration to obtain kinetic information and process parameters. The glass flow reactor set-up is described and combines two types of reaction modules with "mixing" and "linear" microstructures. Finally, the reaction of diphenyldiazomethane with p-nitrobenzoic acid was successfully conducted in the flow reactor, with up to 95% conversion of the diphenyldiazomethane in 11 min. This proof of concept reaction aims to provide insight for scientists to consider flow technology's competitiveness, sustainability, and versatility in their research.

Reaction of Diphenyldiazomethane with Benzoic Acids in Batch and Continuous Flow

“…DDM was prepared in the laboratory by the method described by Aw et al and was purified by crystallization in ethanol . The resulting deep purple DDM crystals were stored at −20 °C in the dark.…”

“…In addition, VIP students carried out the synthesis and analyses of diphenyldiazomethane (DDM) based upon prior art and optimized purification procedures to isolate crystalline DDM product. 38,39 Purposely, the studies were independently led by VIP students with a preagreed timetable, deliverables, and weekly guidance from the mentors and faculties.…”

“…DDM was prepared in the laboratory by the method described by Aw et al and was purified by crystallization in ethanol. 39 The resulting deep purple DDM crystals were stored at −20 °C in the dark. The level of purity varied from batch to batch and was measured for each batch and prior experiments using UV−vis spectroscopy (corrected concentration).…”

“…Under the VIP umbrella and over three semesters, two teams of students (all coauthors of this report) were tasked with (i) designing a flow-chemistry experiment with defined pedagogic learning objectives, (ii) constructing a custom flow reactor to be utilized in the instructional laboratory, (iii) validating the experiment, and (iv) coauthoring the experimental protocols for the undergraduate organic chemistry lab course and this manuscript. In addition, VIP students carried out the synthesis and analyses of diphenyldiazomethane (DDM) based upon prior art and optimized purification procedures to isolate crystalline DDM product. , Purposely, the studies were independently led by VIP students with a preagreed timetable, deliverables, and weekly guidance from the mentors and faculties.…”

“…The rates of reaction (pseudo-first-order and second-order) can thus be experimentally calculated. The batch study is of pedagogic value on its own merit as it provides in-depth understanding of electronic effect, solvent effects, and rate of reactions. , Benzoic acid, p -nitrobenzoic acid, and p -methylbenzoic acid were used as models in the studies conducted by the VIP teams and would be candidates of choice for batch study in instructional laboratories. In this second module, time may permit to setup and prepare the flow tubular reactor (constructed in the prior session or provided prebuilt) by cleaning it with anhydrous ethanol.…”