Multiple reactor synthesizers

In 1992, ACT replaced the Model 350 with the Model 396 Multiple Biomolecular Synthesizer. This instrument possesses two robotic arms, a variable speed orbital mixer, nitrogen assisted bottom filtration, a built-in ventilation system, protocols for both Fmoc and Boc synthesis and fully automated on-board cleavage for the Fmoc syntheses. It has reactor blocks of 8, 16, 40, and 96 wells for the synthesis of peptides from 5 pmol to 1 mmol. The Model 396 MBS also has a heater/cooler option for applications in solid-phase organic synthesis. 

Multiple reactor solid-phase synthesizers provide a high throughput of synthetic biopolymers. The same considerations as for a single synthesis should be applied to a multiple synthesis. The reaction kinetics and reagent requirements are generally quite similar. However, a synthesizer with many reactors often has some major design differences as compared with an instrument that contains only a few reactors. 

A major consideration with a multiple synthesizer is the speed and efficiency of delivery (and removal) of reagents. A 30-s wash step in a single synthesis may seem insignificant, but multiply that by 100 syntheses and the time for the wash step approaches 1 h. The delivery times are often reduced by lowering the scale of the individual syntheses and therefore the amount of reagent required or delivering simultaneously to multiple reactors. 

The continuous and batch microwave reactors have been particularly useful for heating reactions in which thermally labile products are formed. For example, alkyl 2-(hydroxymethyl)acrylates have considerable potential as functionalised monomers and synthons128. Published syntheses at ambient temperature, however, required several days and were not conducive to scale-up129-133. The microwave procedure involved a modified Baylis-Hillman reaction, in which the parent acrylate derivative was reacted with formalin in the presence of 1,4-diazabicyclo [2.2.2] octane (DABCO). Preparations from starting acrylates, including methyl, ethyl and n-butyl esters, were easily achieved within minutes with multiple passes through the CMR, at ca. 160-180°C (Scheme 9.16). Rapid cooling was required to limit hydrolysis, dimerisation and polymerisation. Yields... 

In another example employing multiple supported catalysts and reagents, Smith et al. (2007a) presented a modular flow reactor in which 14 1,4-disubstituted-l,2,3-triazoles were synthesized. Coupling an immobilized copper(I) iodide species 148 with two scavenger modules (immobilized thiourea 149 and phosphane resin 150), the authors reported the [3 + 2] cycloaddition of an array of azides and terminal acetylene (30 pi min x) to afford the desired 1,4-disubstituted 1,2,3-triazoles (Scheme 40) in moderate to excellent yield (70-93%). 

In contrast to single-mode reactors, dedicated multimode instruments allow scale-up to be performed in multivessel rotor systems utilizing various types of sealed vessels. In these systems, reactions can be carried out in batch to synthesize multiple gram quantities (< 250 g) of material in typically up to 1 L processing volume. Most of the multimode instruments available for organic synthesis have been derived from closely related sample preparation equipment [39-41]. The MARS Microwave Synthesis System (Fig. 4) is based... 

A conventional single synthesis system utilizes valves and tubing to route the flow of reagents to the reactor. As the number of reactors increases, it becomes impractical to have valves and tubing for each reactor. To eliminate the need for this added hardware, multiple synthesizers are often based on robotic designs, where the reactors remain stationary in a rack and one or more robotic arms transfer reagents to the individual reactors. The common steps can be expedited by simultaneous delivery to many reactors using... 

It is also important to note that many chemical syntheses involve a number of steps, each carried out under different conditions (and sometimes in different reactors), leading to what we designate as multistep reactions (normally referred to by chemists as a synthetic scheme). This could, for example, be a sequence of reactions such as dehydration, oxidation, Diels-Alder, and hydrogenation. The purpose of this chapter is to outline simple procedures for the treatment of complex multiple and multistep reactions and to explain the concepts of selectivity and yield. 

The main source of transuranium elements is the high-flux reactor, in which or heavier nuclei get transformed into higher-Z elements by multiple neutron capture. In the USA, there is a national program for the production of transuranium elements utilizing the high-flux reactor (HFIR) at Oak Ridge. The heaviest nuclide produced in the reactor is Fm. Neutron-deficient nuclides are synthesized in charged-particle accelerators and very neutron-rich nuclides with short half-lives are produced in reactors. 

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