Microwave using reaction vessels

Microwave-Promoted Carbonylations Using Reaction Vessels Prepressurized with Carbon Monoxide... 

Vessels designed for microwave-assisted SPOS must fulfill several require-menfs because of fhe harsh conditions (i.e., high temperatures and pressures) usually associated with microwave heating. Open vessels are often impractical because of the possible loss of solvent and/or volatile reagents during the heating process. However, in cases where a volatile byproduct inhibits a reaction, their use may be superior over closed systems. A sealed vessel retains the solvents and reagents, but must be sturdily constructed to avoid the obvious safety implications due to the buildup of pressure. 

The cyclization of 1,2-dicarbonyl compounds with aldehydes in the presence of NH4OAC to give imidazoles was employed in a combinatorial study that compared conventional and microwave heating in the preparation of a library of sulfanyl-imidazoles (Scheme 15). The study employed an array of expandable reaction vessels that could accommodate a pressure build-up system for heating without loss of volatile solvents or reagents. A 24-membered library of imidazoles (48 and 49) was prepared in 16 min instead of the 12 h required using conventional heating [45]. 

The common microwave oven has been brought into the laboratory. Using special Teflon reaction vessels, components are mixed together, the vessel sealed and put into the microwave oven. Reaction times are greatly accelerated in many reactions, and reactions that took hours to be complete in refluxing solvents are done in minutes. Benzyl alcohol was converted to benzyl bromide, for example, using microwaves (650 W) in only 9 min on a doped Montmorillonite K-10 clay. This is a growing and very useful technique. 

Similar results were achieved when Biginelli reactions in acetic acid/ethanol (3 1) as solvent (120 °C, 20 min) were run in parallel in an eight-vessel rotor system (see Fig. 3.17) on an 8 x 80 mmol scale [87]. Here, the temperature in one reference vessel was monitored with the aid of a suitable probe, while the surface temperature of all eight quartz reaction vessels was also monitored (deviation less than 10 °C Fig. 4.4). The yield in all eight vessels was nearly identical and the same set-up was also used to perform a variety of different chemistries in parallel mode [87]. Various other parallel multivessel systems are commercially available for use in different multimode microwave reactors. These are presented in detail in Chapter 3. 

The construction of a custom-built parallel reactor with expandable reaction vessels that accommodate the pressure build-up during a microwave irradiation experiment has also been reported [88]. The system was used for the parallel synthesis of a 24-member library of substituted 4-sulfanyl-lH-imidazoles [88]. 

The issue of parallel versus sequential synthesis using multimode or monomode cavities, respectively, deserves special comment. While the parallel set-up allows for a considerably higher throughput achievable in the relatively short timeframe of a microwave-enhanced chemical reaction, the individual control over each reaction vessel in terms of reaction temperature/pressure is limited. In the parallel mode, all reaction vessels are exposed to the same irradiation conditions. In order to ensure similar temperatures in each vessel, the same volume of the identical solvent should be used in each reaction vessel because of the dielectric properties involved [86]. As an alternative to parallel processing, the automated sequential synthesis of libraries can be a viable strategy if small focused libraries (20-200 compounds) need to be prepared. Irradiating each individual reaction vessel separately gives better control over the reaction parameters and allows for the rapid optimization of reaction conditions. For the preparation of relatively small libraries, where delicate chemistries are to be performed, the sequential format may be preferable. This is discussed in more detail in Chapter 5. 

One major benefit of performing microwave-assisted reactions at atmospheric pressure is the possibility of using standard laboratory glassware (round-bottomed flasks, reflux condensers) in the microwave cavity to carry out syntheses on a larger scale. In contrast, pressurized reactions require special vessels and scale-up to more... 

The use of metals or metallic compounds in microwave-assisted reactions can also lead to damage to the reaction vessels. As metals interact intensively with microwaves, the formation of extreme hot spots may occur, which might weaken the vessel surface due to the onset of melting processes. This will destroy the stability of the vessels and may cause explosive demolition of the reaction containers. If catalysts are used which can produce elemental metal precipitates (for example, of palladium or copper), stirring is recommended to avoid the deposition of thin metal layers on the inner surfaces of the reaction vessels. 

The same Suzuki couplings could also be performed under microwave-heated open-vessel reflux conditions (110 °C, 10 min) on a ten-fold larger scale, giving nearly identical yields to the closed-vessel runs [33, 35], Importantly, nearly the same yields were obtained when the Suzuki reactions were carried out in a pre-heated oil bath (150 °C) instead of using microwave heating, clearly indicating the absence of any specific or non-thermal microwave effects [34],... 

However, several articles in the area of microwave-assisted parallel synthesis have described irradiation of 96-well filter-bottom polypropylene plates in conventional household microwave ovens for high-throughput synthesis [16-19]. While some authors have not reported any difficulties associated with the use of such equipment [19], others have experienced problems in connection with the thermal instability of the polypropylene material itself [17] and with respect to the creation of temperature gradients between individual wells upon microwave heating [17, 18]. While Teflon (or similar materials such as PFA) can eliminate the problem of thermal stability, the issue of bottom-filtration reaction vessels has not yet been adequately addressed. 

A prototype of a microwave reaction vessel that takes advantage of bottom filtration techniques was presented by Erdelyi and Gogoll in a more recent publication. Therein, the authors described the use of a modified reaction vessel (Fig. 7.2) for the Emrys instruments (see Section 3.5.1) with a polypropylene frit, suitable for the filtration /cleavage steps in their microwave-mediated solid-phase Sonogashira coupling (see Scheme 7.19) [21]. 

The MARS-S is constituted of a multimode cavity very close to domestic oven with safety precautions (15 mL vessels up to 0.5 L round-bottomed flasks, magnetic stirring, temperature control). The magnitude of microwave power available is 300 W. The optical temperature sensor is immersed in the reaction vessel for quick response up to 250 °C. A ceiling mounted is available in order to make connection with a conventional reflux system located outside the cavity or to ensure addition of reactants. These ports are provided with a ground choke to prevent microwave leakage. It is also possible to use a turntable for small vessels with volumes close to 0.1 mL to 15 mL vessels (120 positions for 15 mL vessels). Pressure vessels are available (33 bar monitored, 20 controlled). 

Although microwave-heated organic reactions can be smoothly conducted in open vessels, it is often of interest to work with closed systems, especially if superheating and high-pressure conditions are desired. When working under pressure it is strongly recommended to use reactors equipped with efficient temperature feedback coupled to the power control and/or to use pressure-relief devices in the reaction vessels to avoid vessel rupture. Another potential hazard is the formation of electric arcs in the cavity [2], Closed vessels can be sealed under an inert gas atmosphere to reduce the risk of explosions. 

The issue of parallel versus sequential synthesis using multimode or monomode cavities, respectively deserves special comment. While the parallel setup allows for considerable throughput that can be achieved in the relatively short timeframe of a microwave-enhanced chemical reaction, the individual control over each reaction vessel in terms of reaction temperature and/or pressure is limited. In the parallel... 

---