Scale‐Up of Microwave‐Assisted Organic Synthesis

Abstract

In 1986 it was first reported that organic reactions could be conducted by heating in sealed containers in domestic microwave ovens 1,2 . Rate enhancements of up to three orders of magnitude were disclosed 3 . However, temperature and pressure measurement were technically difficult to achieve and in some instances the vessels deformed or exploded 1-3 .From these publications, workers interested in exploring the microwave technique perceived it to be simultaneously beneficial through increased rates, yet hazardous in the presence of flammable organic solvents. Subsequently, a vast body of work was carried out with domestic microwave ovens, but under solvent-free conditions and without recourse to sample mixing or temperature measurement. This continued across a broadening front on the laboratory scale. These and other developments in microwave chemistry have been reviewed extensively in journals, book chapters 4-20 and in a recent monograph 21 .Although relatively inexpensive in terms of purchase price, domestic microwave ovens are not designed to contain chemical explosions or toxic fumes and are incompatible with corrosive and inflammable compounds 13 . Flux densities within the microwave cavity can vary considerably, resulting in 'hot' and 'cold' spots. Mode stirrers and circulation of the vessel within the cavity are sometimes incorporated to assist in overcoming the non-uniformity of the energy distribution, but such measures are usually inadequate. Domestic ovens operate on duty cycles and intervals between zero and full power can be many seconds. This is not always ideal for heating common foods and beverages, let alone for performing delicate chemical manipulations. Intermittent bursts of power afford poor temperature control in chemical reactions. When these matters are considered in conjunction with the initial lack of dedicated pressure vessels for microwave-assisted organic chemistry, it is not surprising that explosions occurred 1-3 and that reactions are not necessarily reproducible in domestic microwave systems 6 .During the decade after 1986, disadvantages of domestic microwave ovens for organic chemistry became apparent to many researchers. Because of the unavailability of specifically designed commercial equipment, however, workers with volatile organic solvents, still found it necessary to adapt domestic units for reflux conditions or for operations under pressure. For reactions at reflux 22-30 , domestic microwave ovens were modified by fitting with a shielded opening to prevent microwave leakage and through which the reaction vessel within the microwave cavity could be connected to an external condenser 22,23,30 . Commercial systems adopting this approach have since appeared. When microwave-transparent coolants (chilled hydrocarbons, ice or solid carbon dioxide) are used, along with the reaction vessel, the condenser can also be located within the microwave cavity, thereby avoiding potential problems with microwave leakage 26,29,31 . 237Microwave Assisted Organic Synthesis Edited by Jason P. T...

On Scale Up of Organic Reactions in Closed Vessel Microwave Systems

“…This may have occurred in part through perceived limitations of the technique as discussed below, but not entirely. Different perspectives of chemists and chemical engineers in chemical discovery and manufacturing respectively, also may have had an influence . A limited knowledge of the reaction conditions may be sufficient to enable synthetic chemists to obtain a desired product in the laboratory.…”

“…The time might seem ideal for scaling up capacity for microwave reactions by at least an order of magnitude above the kilogram level. Doubts have been expressed, however, that scale up may not be feasible owing to insufficient depth of penetration of microwaves, ,,, heating rates being too slow to offer advantages, the cost of generating microwave energy being too high, , and the significant engineering challenges associated with safely heating reactions under pressure in large, microwave-transparent vessels …”

“…A key determinant of the scope of microwave chemistry, though, will be the highest scales that can be accommodated. Scale up with existing microwave technologies is discussed herein, and uncertainties regarding extension of microwave capabilities beyond the laboratory scale ,− are addressed.…”

Large-scale microwave-assisted ring-opening polymerization of ɛ-caprolactone

“…With reference to the successful small-scale examples, the larger scale microwaveassisted synthesis technology that can economically provide product on a multikilogram scale (or even higher) need to be developed for making it to become widespread technology in the future. Actually, for the ability of the direct homogenous heating of the reaction mixtures under microwave irradiation to facilitate direct scaling without heat and mass transport issues [7], several reports have demonstrated the feasibility of direct scaling reaction conditions from small-scale single-mode (0.5-5 mL) to larger scale batch modes (10-500 mL), such as multimode [8][9][10][11][12][13][14], monomode [15,16] and continuous-flow microwave reactors [17][18][19][20], without reoptimization of the reaction conditions. The larger scale microwave-assisted polymerizations (250-400 mL) have also been performed in domestic microwave ovens that equipped with reflux condensers [21,22].…”

Microwave Activation of Alumina and its use as a Catalyst in Synthetic Reactions

“…We thus have examined microwave heating as a simpler, more readily available methodology for activating the solid. [6][7][8] We have tested this idea on the extensively studied Diels-Alder reaction [9][10][11][12][13][14][15][16] and Claisen rearrangement. [17][18][19][20][21][22][23] We have previously examined in detail the Diels-Alder reaction on thermally activated alumina, [24][25][26][27][28][29][30] but the Claisen rearrangement is new to us.…”