Which reaction finishes faster ? Comparison of conventional, microwave and continuous flow reaction. (OLD)

I might need some time get some new literature to review.  But here is a paper I found a while ago, comparing conventional batch reactions, with microwave and continuous flow.

 

It is often the case that we, as chemists, often forget about the other types of processes that exist out there or were never introduced to anything other than the batch reaction.  By nature, we all typically run a batch reaction most of the time.  It was what we were taught in undergraduate and graduate studies.  No one ever told us you could pump your reagents into a mixing T if it was a kinetically “fast” reaction and out comes your product.  I am fairly interested in microreactors in which you could basically take up very little space, control exotherms and be able to make grams and grams of product.    I have to fess up that I have only done batch processes and it has been my sole experience to do reactions as a batch process.  So how good can a continuous flow process be ?  What if there was a paper that compared a conventional reaction with a microwave assisted reaction to a continuous flow reaction ? (okay, I will end the foreshadowing, I am sure you get it).   I have talked about continuous flow before, for example, here (https://developingtheprocess.wordpress.com/2014/07/04/a-palladium-wall-coated-microcapillary-reactor-for-use-in-continuous-flow-transfer-hydrogenations/)

Today’s post was an article I found in the Journal of Organic Chemistry, “Synthesis of 3-Aryl/benzyl-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d ]isoxazole Derivatives: A Comparison between Conventional, Microwave-Assisted and Flow-Based Methodologies” by Paola Conti et al, J. Org. Chem., 2010, 75, 7439-42.  You could look at this article as a case study for continuous flow reactions.  The central reaction for this paper is the following reaction.

 

cycloadd

 

There is only one thing I want to say before I show you all the data.  There has been some research made in the direction of applying microwave technology to process chemistry.   The idea is exciting; I personally don’t know at what stage of development microwave reactors are at.  I have personally used a microwave to provide product from a Suzuki coupling reaction in under 30 minutes, on a gram scale.  Running this reaction with conventional heating took 48 hours.  Everyone thinks that microwaves are the best thing since sliced bread. However………….

Back to the paper.  So, I will provide you with the conventional reaction conditions as follows:

cycloaddtable1

In this experiment, they are using excess NaHCO3 as a base ( 4 equivalents).  The yields don’t look so hot after 7 days !!!!  The authors show that they can get the same yield by reducing the equivalents of chloroxime by half and refluxing the reaction for 3 days (maybe adding 1 % water).  At least, that is better than 7 days.  After using the microwave, with 3 x 0.5 hr heating cycles, they are able to yields of 47-67 %.  Quite a bit better than the conventional heating process.  But you would expect that right, now for what I wasn’t expecting.

I will describe the continuous flow setup the author was using and then their results.

The author describes a procedure in which the reactants are dissolved in ethyl acetate in a concentration of 0.25 M, although the chloroxime’s concentration was increased 1.5 times to optimize the reaction.  The two flow streams are pumped into a simple T and the output is directed through a glass column containing solid potassium carbonate heated to 80 °C.  Although the residence time was initially set at a residence time of 30 min, 10 minutes was optimal.

The yields for this reaction with a residence time of 10 minutes was 60-73 % !!!  Unbelievable.  That was quite impressive and a great application of using continuous flow.  Stay tuned for the next posting and have a great weekend.

schematic

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