Parallel Synthesis

Parallel synthesis is a common strategy, generally used to complement combinatorial techniques. Parallel synthesis often is the first step toward producing larger yields of materials identified from discovery screening tests, and for scaling up to production level quantities. Parallel synthesis typically involves multiple reactions of mixtures in the tens of milliliters. Milestone provides a variety of rotors to support your specific parallel synthesis requirements.

The PRO-6 Rotor

The PRO-6 rotor is the 6-position parallel version of Milestone's MonoPREP module, which is designed for safe reaction optimization at elevated temperatures and pressures, using a single 12 ml or 50 ml glass or quartz reactor vessel. The MonoPREP, with its very fast cooling (close to 30 °C/min), support for small volumes (as low as 2 ml), and choice of glass or quartz reactor vessels, is one of the most popular accessories in Milestone's wide range of tools.

The PRO-6 carries all the benefits of the MonoPREP into a parallel format. With this unique rotor, the medicinal chemist can simultaneously process up to 6 identical or similar samples—varying, for example, the stoichiometry of the reaction—at atmospheric pressure or up to 15 bar (225 psi).

The PRO-16 Rotor

The innovative PRO reactor vessel is Milestone's newest, most advanced and safest reactor for high-throughput purposes. The patented pressure release valve in each reactor will vent and reseal automatically when pressure inside the vessel reaches 20 bar (280 psi). No sample will be lost, as it would with burst disks or membranes. The reactor also features simplified, "wrench-free" handling; it can be sealed or unsealed in just 5 seconds.

The PRO-16 Rotor can process samples in 16 such reactors simultaneously, with the option of adding up to 8 more. It permits internal temperature and pressure monitoring, for precise reaction control. The entire rotor, with TFM vessels, can also be cooled in a water bath for quick turn-around in high-throughput environments.

The High-Pressure 100 mL Rotor

For work at extremely high pressures, there is no better choice than the HPR 100 mL Rotor. This rotor accommodates 10 individual reactors (included in our Med Chem Kit), each of which can be individually inserted and removed. Pressures up to 100 bar (1500 psi) can be sustained.

Parallel Synthesis Rotors
	PRO-6 Rotor	PRO-16 Rotor	HPR 100 mL Rotor
Reaction Vessels	6	16 or 24	10
Vessel Volume	12 or 50 mL	70 mL	100 mL
Minimum Operating Volume	3 mL	10 mL	10 mL
Vessel Material	Glass or Quartz	TFM
Maximum Operating Temperature	180 °C	200 °C	300 °C
Maximum Operating Pressure	15 bar (225 psi)	20 bar (290 psi)	100 bar (1500 psi)
Internal Temperature Control	Fiber optic in one reference reactor
External Temperature Control	Infrared on all reactors
Magnetic Stirring	Liquid and slurries in all reactors

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In Support of Parallel Synthesis

Parallel reactions can be performed in formats of 6, 10, 16, or 24 glass, quartz, or TFM reactor vessels simultaneously, at atmospheric pressure or up to 50 bar internal pressure or greater. The multi-mode MicroSYNTH labstation generates a uniform, continuously stirred microwave field, with no hot or cols spots, making it possible to process multiple samples at once, or to scale up the reaction volume.

The unique, patented vent-and-reseal covers in all of Milestone's parallel rotors support elevated internal pressures, and allow reaction temperatures above the normal boiling point of the reaction mixtures. Pressure is vented with no loss of sample, and unlike single-use consumables, Milestone's reactors can be used again and again.

The 12 and 50 ml vessels, and the PRO reactors, feature easy "wrench-free" handling. One can easily add another reagent to the reaction mixture, or take a sub-sample for quick thin layer or NMR analysis, then reclose the vessel and restart the synthesis.

Stirring ensures homogeneous reaction mixtures, even bi-phasic mixtures of liquids and slurries. Magnetic stir bars can be used in each vessel, in conjunction with the variable speed stirring available in every MicroSYNTH Labstation.

There is no need to alter your existing chemistry, even if you use non-polar (i.e., microwave-transparent) solvents. Milestone's unique high-purity Weflon buttons make it easy to adapt conventional chemistry to the microwave. Weflon (carbon-impregnated Teflon) can function as a microwave absorber and transfer heat to the reaction mixture.

Controlled reaction temperatures to 200 °C are possible. Accurate temperature monitoring and precise feedback control is achieved using a fiber-optic temperature probe inserted into a reference vessel. Alternatively, a contactless infrared sensor can be used to monitor all of the reactors simultaneously.

This temperature monitoring enables the easyWAVE software to follow a pre-programmed temperature profile with great precision, resulting in reproducible reaction temperature conditions, ± 1 °C precision. An added advantage is that in the case of an exothermic reaction the microwave will shut down immediately, allowing the reaction to slow down, preventing a loss of sample or, worse, an explosion.

The facility to create a controlled-intensity mercury vapor spectrum, to induce photochemical reactions in each vessel, can be achieved through the use of electrodeless plasma lamp inserts.

 

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