Evaluation of a Nonresonant Microwave Applicator for Continuous-Flow Chemistry Applications

Abstract

The concept of a nonresonant microwave applicator for continuous-flow organic chemistry is introduced and evaluated. The frequency of the incident microwave radiation can be adjusted between 2.4 and 2.5 GHz to optimize the energy absorbance. The temperature of the reaction is monitored by five IR sensors, and their signals can be used to automatically adjust the power output from the microwave generator. The heating of several different solvents up to 20°C above the standard boiling point has been explored. Several different organic reactions have been successfully carried out using a 200 mm × ⌽ 3 mm tubular borosilicate reactor and a flow between 47 and 2120 μL/min. The microwave heating pattern was visualized with an IR camera. The transformations include palladium-catalyzed coupling reactions (oxidative Heck and Suzuki reactions), heterocyclic chemistry (oxathiazolone and Fischer indole synthesis), rearrangement (Claisen), and a Diels−Alder cycloaddition reaction. A scale-out to 57 mmol/h was performed with the Fischer indole reaction.

Chlorocarbonylsulfenyl Chloride Cyclizations Towards Piperidin-3-yl-oxathiazol-2-ones as Potential Covalent Inhibitors of Threonine Proteases

“…35 Nitrile sulphides are short-lived species prone to fragmentation and can take part in further cycloadditions. [36][37][38] After initial unsuccessful attempts to prepare the desired compounds 3a-f, we turned our attention to microwave-assisted report on flow-chemistry synthesis of oxathiazol-2-one in dioxane at 200 °C and residence time of 1 min in a flow reactor reported by Öhrngren et al 39 On this basis, we modified the reaction procedure and dissolved the carboxamides 2a-f (Figure 4) in dry dioxane (27 mL/1 mmol carboxamide), used an excess of solid Na-2 CO 3 (5 eq) and chlorocarbonylsulfenyl chloride (2 eq), and stirred the reaction mixture at 100 °C for 16 h under argon to obtain the desired oxathiazol-2-ones 3a-f ( Figure 4) in 16 to 68% yields (Table 1).…”

Microwave‐Heated Transition Metal‐Catalyzed Coupling Reactions

“…Recently, a new non-resonant CF prototype instrument designed for performing organic synthesis was described [31]. This instrument was shown to provide uniform heating over at least a 100 mm section of a glass reactor.…”

“…in DMF-water (95:5) were simultaneously pumped into the reactor at 150 • C with a 30 s residence time. This afforded 4-methoxy-4 -(methoxymethyl)-1,1 -biphenyl in an isolated yield of 71% and with a calculated throughput of 3.0 mmol h −1 (0.69 g h −1 ) [31]. Notably, the 30 s residence time represents a considerable reduction compared with the 8 and 4 min reported previously by Wilson et al [29] and Comer and Organ [28] with laboratory-scale CF systems using modified single-mode microwave batch applicators.…”

Microwave-assisted Cu-catalyzed Ullmann ether synthesis in a continuous-flow milli-plant

“…[30][31][32] Since for most organic solvents the penetration depth of microwaves is of the order of centimetres the optimum microwave-assisted reactor for organic reactions is characterized by reactors with the same or smaller dimensions [33,34]. At these reactor sizes microwaves, acting as a volumetric heating source, do not suffer from heat-transfer resistance and, combined with a proper reaction medium, provide opportunities to heat the reaction mixture rapidly and efficiently ( Figure 1a).…”