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Process Chemistry Links Controlled Lab Reactors Process Optimisation Flow Chemistry Calorimetry logP Aqueous work up Parallel Process PRODUCTS Syrris Launch High Performance Atlas Calorimetry System
Atlas Volumetric Dosing System comes with FREE Temperature Probe worth over £500
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Reaction Optimisation Example 1The AFRICA system is ideally suited to automated reaction optimisation. Parameters such as time, temperature, equivalents of reagents and order of addition can be easily investigated. To demonstrate this a Passerini 3CR reaction in the literature1 that was part of a library of compounds was optimised. The objective was to optimise the procedure to reach the highest yield of desired product with a maximum of 1 hr reaction time.
The literature1 reaction conditions were 60 hrs at room temperature with a 1:2:1 ratio of acid:aldehyde:isonitrile. These conditions were repeated at Syrris and generated a yield of 62% (determined by HPLC with a calibrated internal standard). A design of experiment consisting of 16 reactions was carried out to investigate the following four variables within the specified ranges: Time: 15, 30 and 60 mins - Due to the unacceptably long time for the literature batch reaction, a maximum of 1 hour was decided upon for the flow reaction. Temperature: 80°C and 100°C - To reduce the reaction time to below 1 hour, the minimum temperature chosen was 80°C. The maximum of 100°C was defined due to the capacity of the AFRICA system with DCM (Dichloromethane). Note that the temperatures are significantly greater than the atmospheric boiling point of DCM, which is 40°C. Equivalent ratios: Equivalents of isonitrile (vs acid): 0.7, 1 and 1.3 equivalents, and equivalents of aldehyde (vs acid): 0.7, 1 and 1.3 equivalents - it was decided that a very large equivalent of any reagent would not be investigated due to the poor efficiency of using large excesses. By running these conditions automatically in AFRICA, the optimum conditions within the boundaries set were found to be 60 mins, 80ºC, 1:0.7:1.3 acid:aldehyde:isonitrile, giving a yield of 91%. The reaction was therefore optimised from a batch reaction of 62% (60 hr reaction) to 91% yield (1 hour reaction) using the AFRICA system and a DoE approach.
A schematic taken from the AFRICA software By running these conditions automatically in AFRICA, the optimum conditions within the boundaries set were found to be 60 mins, 80ºC, 1:0.7:1.3 acid:aldehyde:isonitrile, giving a yield of 91%. The reaction was therefore optimised from a batch reaction of 62% (60 hr reaction) to 91% yield (1 hour reaction) using the AFRICA system and a DoE approach. |
