Reaching the Next Level of Microwave-assisted Organic Synthesis

Microwave-assisted organic synthesis (MAOS) has become an increasingly popular discipline in modern chemical method development. This means that a modern, "dedicated" microwave reactor must provide also stirring, temperature measurement and pressure sensing. In the last decade, demands from scientific researchers for appropriate reaction control have lead to the development of several sophisticated microwave instruments specially designed for synthesis applications. At first, reaction optimization and method development on a small scale were the main areas of interest in MAOS. However, the growing acceptance and success of this innovative microwave technology revealed the necessity for large-scale synthesis of valuable compounds using microwave heating, especially in industrial laboratories.

To meet these needs, Anton Paar introduces the Synthos 3000 multimode batch reactor, which enhances the performance of microwave-assisted organic synthesis towards multi-gram production under sealed vessel conditions. This new microwave platform is dedicated to the organic synthesis of hundreds of grams of products in one run. No re-optimization of promising protocols is needed when moving from development to the production stage. The Synthos 3000 also ensures the interchangeability of procedures when switching from single-mode to multimode instruments.

General Features & Applications
The Synthos 3000 is a multimode batch reactor, delivering 1400 W unpulsed microwave output power via two powerful magnetrons (850 W each). The resulting homogeneous microwave field guarantees identical conditions throughout the large 66 L cavity and therefore excellent reproducibility of the performed reactions. A precise dual temperature measurement utilizing an immersing gas-bulb thermometer and a bottom-mounted IR sensor as well as integrated hydraulic pressure sensing ensure optimum reaction control during the entire process.

The novel gas-bulb thermometer takes advantage of the linear correlation between temperature and pressure according to the ideal gas equation (p·V = n·R·T). An interference-free, hermetically sealed glass bulb is filled with gas which tries to expand when warmed up during the reaction. This prevented expansion causes a pressure increase which is transferred to an electronic transducer via a capillary tube. The sensed pressure increase is then converted into the corresponding temperature value and transmitted to the electronics module. This guarantees the immediate response and utmost accuracy ( 1 °C) of the sensor, which is protected by a microwave-transparent sapphire tube.

Precise pressure sensing is achieved by a combined pressure/temperature sensor accessory in one reference vessel for the 16-position rotor or by the simultaneous measurement at all positions of the 8-position rotor. In this 8-position rotor, all positions are connected via the hydraulic system (integrated in the rotor top plate) and the highest sensed pressure is displayed on the screen. This ensures optimum reaction control as the system records pressure increase in any of the vessels and regulates the power output according to the adjusted limits.

All sensed data are transmitted wirelessly via IR remote control to the PC controller, without disturbing cable connections inside the cavity.

Two different rotor types, several kinds of interchangeable vessels and various sophisticated accessories make the Synthos 3000 a powerful platform in the synthetic laboratory. The vessels are hermetically sealed by easy-to-use lip-type seals integrated in the vessel caps. These allow reaction conditions up to 80 bar and 300 °C, which enable the development of completely new microwave-mediated reaction protocols. The homogeneous field allows you to apply different substrates within one run for the generation of small product libraries in multi-gram size (>10 g per vessel). Employing identical substrates in the individual vessels yields several hundreds of grams in a single experiment, depending on the conversion rate of the reaction. The minimum amount of 6 mL per vessel also allows for carrying out optimization reactions, although the instrument is specifically designed and dedicated for efficient large-scale synthesis.

The vessels for Rotor 16 (MF/HF100) comprise a 100 mL PTFE-TFM liner, a corresponding pressure jacket (either PEEK or ceramic) and a suitable screw cap containing the lip-type seal, safety disk, venting screw, and syringe adapter. The high-performance vessels for Rotor 8 consist of either the same set-up with liner and ceramic pressure jacket, coated with an additional PEEK protective jacket (XF100) or 80 mL quartz glass vessels immersed in the PEEK jacket for appropriate stability (XQ80). The containers are closed with different types of sealing caps, as the quartz vessels could not be equipped with a corresponding thread, and covered with a PEEK protective cap for final assembly.

The rotors are closed with a bayonet-type protective lid for comprehensive safety. Reflection marks are used to identify the rotor by the software in order to prevent misuse of a rotor for inappropriate methods.

Sophisticated Accessories
Special applications such as solid-phase synthesis, UV photochemistry or pre-pressurizing of the reaction vessels can be performed efficiently and with ease. It's a fact that the Synthos 3000 features the highest temperature/pressure conditions for synthesis instruments on the market. Operation limits of 80 bar at 300 °C for more than 60 minutes enable reactions even at near critical water conditions (>250 °C, >60 bar) - an emerging field of interest in organic chemistry. In addition, the easy-to-handle gas loading system allows you to create individually inert or reactant gas atmospheres in every single vessel. The already charged and closed reaction vessels are placed in the rotor and the gas loading is achieved safely via the closed protection lid. Pressures up to 20 bar can easily be applied prior to reaction, simplifying experiments employing gaseous reagents.

The robust, non-adhesive PTFE liners enable comfortable handling of polymer-supported reagents in large amounts as the vessels can be charged with up to 5 g solid support each. Employing the sophisticated filtration unit allows subsequent washing and cleavage steps without changing the reaction vessel, maximizing the yield by minimizing the handling steps. This tool can also be used to separate precipitated products after the reaction. Various filter types make it appropriate for different kinds of solid compounds. Applying up to 5 bar external pressure makes the filtration step convenient and easy.

Safety Aspects
User safety in case of unforeseen spontaneous reactions is one of the major concerns in microwave-assisted chemistry at elevated conditions. To ensure the highest level of user protection, the Synthos 3000 provides a multi-step safety package with several active and passive safety measures. Besides preventing pressure peaks by sophisticated software-aided reaction control, a stepwise and controlled release of the built-up overpressure is the key to ultimate safety levels. The robust impact-resistant safety door with electrical and mechanical (magnetic) interlocks automatically reseals the cavity after a spontaneous pressure release. To prevent the vessels rupturing, the sealing caps are equipped with durable metal safety disks. These open at 70 bar (16-position rotor) or 120 bar (8-position rotor), therefore providing an extensive overpressure tolerance compared to the controlled pressure limits. As all vessel types withstand pressures up to 140 bar there is still sufficient tolerance before potential destruction of the vessels. Software-controlled pressure rate enhancement and accurate temperature limitations efficiently protect the entire equipment from damage, as a build-up of significant overpressure will be prevented by effective decrease of the power output if any control limit is reached. Finally, the cage-like design of the rotors with the protective lid prevents debris being released outside the cavity.

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