Laboratory Ozonolysis Using an Integrated Batch–DIY Flow System for Renewable Material Production

Abstract

Flow chemistry offers a solution for replacing batch methods in chemical preparation where intermediates or products may pose toxicity or instability hazards. Ozonolysis offers an ideal opportunity for flow chemistry solutions, but multiple barriers to entry exist for use of these methods, including equipment cost and performance optimization. To address these challenges, we developed a programmable DIY syringe pump system to use for a continuous flow multireactor process using 3D-printed parts, off-the-shelf stepper motors, and an Arduino microcontroller. Reaction kinetics of ozonide formation informed the use of an integrated batch–flow approach, where ozone addition to an olefin was timed to coincide with fluid movement of a single-syringe pump, followed by downstream Pinnick oxidation and reductive quench in flow. The system was demonstrated by continuous preparation of azelaic acid from ozonolysis of palmitoleic acid, a process limited to low production volumes via batch chemistry. High total production of azelaic acid with 80% yield was obtained from an algae oil sourced unsaturated fatty acid: a product with important applications in medicine, cosmetics, and polymers. This low-cost, scalable approach offers the potential for rapid prototyping and distributed chemical production.

Synthesis of Acid Hydrazides from Carboxylic Acids in Continuous Flow

“…Algaederived azelaic acid was prepared following a previously reported procedure by our group. 13 The procedure detailed above was identical using (5.0 g, 26.6 mmol, 1 equiv) algaederived azelaic acid (5.0 g, 26.6 mmol, 1 equiv). 3 was isolated as a white powder (5.0 g, 23.3 mmol) in an 88% yield.…”

“…Deuterated solvents (CDCl 3 and DMSO-d 6 ) were purchased from Cambridge Isotope Laboratories. 1 H NMR and 13 C NMR spectra were recorded on a Bruker AVA 300 or JOEL ECA 400 MHz spectrometer. Coupling constants (J) are reported in Hz.…”

“…Optimization tables and procedures, photographs of the flow chemistry setup, and copies of 1 H and 13 C NMR spectra (PDF)…”

“…The inspiration for this current work stems from the practical need for a scalable process to dihydrazide 3 from azelaic acid ( 1 ), a renewably sourced diacid that we derive from algae-sourced palmitoleic acid via ozonolysis. , Traditionally, acid hydrazides are synthesized via a two-step process in batch, wherein a carboxylic (either mono- or di-) acid is first converted to its ester or acid chloride and then treated with hydrazine hydrate at elevated temperatures. , Although this process is effective on smaller gram scales in the laboratory, larger-scale production of dihydrazides following this approach is both time-consuming and energy-intensive given the need to work up and isolate the ester or acid chloride intermediate. Additionally, handling large quantities of hydrazine hydrate at high temperatures in a batch reactor poses safety concerns .…”

Effect of Solvent on the Rate of Ozonolysis: Development of a Homogeneous Flow Ozonolysis Protocol

“…To circumvent these issues, continuous flow reactors have shown promising results in the large-scale preparation of several small molecules, such as azelaic acid 4 (Figure ). , The use of heterogeneous annular, slug, membrane, and solid supported flow systems has enabled significant progress in this regard. However, several drawbacks limit the utilization of these processes (Figure A). – For instance, ineffective mixing of gaseous O 3 /O 2 mixtures with the dissolved substrate in the liquid phase often results in low conversions .…”