Safe, Selective, and High‐Yielding Synthesis of Acryloyl Chloride in a Continuous‐Flow System

Abstract

Acid chlorides are an important class of compounds and their high reactivity and instability has prompted us to develop a straightforward procedure for their synthesis with on-demand and on-site synthesis possibilities. The focus of this report is acryloyl chloride, mainly important for the acrylate and polymer industry. A continuous-flow methodology was developed for the fast and selective synthesis of the otherwise highly unstable acryloyl chloride. Three routes were investigated in a microreactor setup and all three can potentially be used for its production. The methodology was further expanded to the synthesis of other unstable acid chlorides by both the thionyl chloride and the oxalyl chloride mediated processes. The most sustainable method was the oxalyl chloride mediated procedure under solvent-free conditions, in which near-equimolar amounts of carboxylic acid and oxalyl chloride were used in the presence of catalytic amounts of DMF at room temperature. Within 1 to 3 min, nearly full conversions into the acid chlorides were achieved.

Design and synthesis study of the thermo‐sensitive copolymer carrier of penicillin G acylase

“…The synthesis of acryloyl chloride was accorded to literature; firstly, a mixture of acrylic acid (61 mL), benzoyl chloride (140 mL), and of hydroquinone (0.25 g) was loaded in a single‐necked flask equipped with a rectifying column, a thermometer, and a set of evaporation equipment, and the flask was fixed on an oil bath of 80°C which was set on a magnetic stirrer. During reaction, the temperature of thermometer was detected; as the temperature of thermometer was arrived at 63°C, the fraction was collected by a 2‐necked flask, and the other port was spiked with a spherical anhydrous calcium chloride drying tube to prevent from the outside air humidity.…”

“…The synthesis of acryloyl chloride was accorded to literature 55 introduced, the reaction was kept for 6 hours in the ice-water bath with stirring. After that, the mixture was filtered, and distilled water (100 mL) was introduced into the filtrate.…”

Atom‐ and Mass‐economical Continuous Flow Production of 3‐Chloropropionyl Chloride and its Subsequent Amidation

“…Near equimolar amounts of chlorinating reagents were thus used. Small amounts of N , N ‐dimethylformamide as catalyst was previously proven to be of great benefit for the continuous flow acid chloride formation, and it was thus further used in this work …”

“…Small amounts of N,N-dimethylformamidea s catalystw as previously proven to be of great benefit for the continuous flow acid chloride formation, and it was thus further used in this work. [1] The synthesis of 3-chloropropionyl chloride 2 with phosphoryl chloride, oxalyl chloridea nd thionyl chloride was assessed by varying three parameters:t emperature, residence time and system pressure. Twos eparate( syringe or dual syringe) pumps were used to introduce the acid and the chlorinating reagent into ac apillaryf low reactor via aT -junction (Scheme 1).…”

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

“…However, we wanted to use m -(chlorosulfonyl)benzoyl chloride since this can be synthesized in one single step. Furthermore, acid chlorides show a high reactivity [21] making m -(chlorosulfonyl)benzoyl chloride an ideal starting material as was shown by Yang et al [18]. By transferring this reaction to a multistep flow set-up, we envisioned an improved chemoselectivity.…”