Application of Focused Microwaves to the Scale-Up of Solvent-Free Organic Reactions

Abstract

A series of typical solvent-free reactions have been safely and beneficially scaled-up to several hundred grams in a larger batch reactor (Synthewave 1000) with yields equivalent to those obtained under similar conditions (temperature, reaction time) in laboratory-scale experiments (Synthewave 402). They concern potassium acetate alkylation, regioselective phenacylation of 1,2,4-triazole, deethylation of 2-ethoxy-anisole, and typical examples in carbohydrate chemistry (peracetylation, glycosylation, saponification, halogenation, and epoxidation of Dglucopyranosides).

Reproducibility and Scalability of Microwave-Assisted Reactions

“…Scheme 1. Synthesis and scale-up of dioxolanes, dithiolanes and oxathiolanes Similar results were reported by Loupy for the reproducibility and scale-up of several reactions (potassium acetate alkylation, regioselective phenacylation of 1,2,4-triazole, deethylation of 2-ethoxyanisole, and typical examples in carbohydrate chemistry) to several hundred grams in a larger batch reactor (Synthewave 1000), with yields equivalent to those obtained under similar conditions (temperature, reaction time) in laboratory-scale experiments (Synthewave 402) (Cléophax et al, 2000). Luthman studied the appropriate reaction conditions in terms of choice of solvent, reaction temperature and reaction time to allow the fast and reproducible production of Mannich bases from small (2 mmol) to large (40 mmol) scale reactions in moderate to high yields (18-60%) and high purity (F. Lehmann et al, 2003) (Scheme 2).…”

“…In fact, this combination of batch synthesis and parallel processing can furnish either compound libraries on the gram scale or a larger amount of one single compound in a short time. Although the Milestone UltraCLAVE system provides a 3.5 L single vessel cavity, it has proven to be more effective to heat smaller volumes in parallel rather than one big batch, given that identical microwave output power is applied (Loones et al, 2005;Cléophax et al, 2000). The demands made on industry, especially the pharmaceutical industry, are changing at an unprecedented pace, making speed critical in modern chemistry.…”

Eco-friendly synthesis of pyrazoline derivatives over potassium carbonate

“…9 Further attractions of this method are that it permits reactions in open vessels (thus avoiding the risk of high pressure developing) and synthesis on preparative scales. 10 In view of the above, and in continuation to our earlier work on the application of MORE 11 chemistry to organic synthesis and the biological importance of pyrazolines, we now report a simple microwave synthesis of pyrazolines 4a-j from chalcones 3a-j and thiosemicarbazide over potassium carbonate (K 2 CO 3 ) . The desired chalcones 12 3a-j were synthesized by reacting 2,4-dichloro-5-fluoroacetophenone 1 with aromatic aldehydes 2a-j in the presence of alkali.…”

Reproducibility across Microwave Instruments: First Example of Genuine Parallel Scale up of Compounds under Microwave Irradiation

“…For instance, scale-up of reactions has been recently described [7,8]. Loupy et al have reported the scale up of solvent-free reactions using focused microwave instruments [7], and Kappe et al have described the scale up of solution phase and solid phase reactions combining single-mode and multimode microwave ovens: single-mode for optimization of the reaction and multimode for its scale up [8].…”