Wednesday, March 7, 2012

Process Wednesday: more on micro- and macro-mixing

Credit: Hartman et al. Angew. Chem. Int. Ed. 2011, 50, 7502-7519.
To continue our conversation about mixing from last week, here's a really nice set of pictures on the relative lack of mixing in a 20 L vessel from a ACIE review [1]:
A fluorescent dye (rhodamine G) was injected close to the shaft of a single impeller into the 20 L vessel filled with glycerin. Exposure to UV light illustrates a sequence of snapshots taken at 3, 5, 10 and 30 seconds as the dye was dispersed inside the vessel. A pattern of nested spirals is observed after 30 seconds while Figure 3e shows the formation of a helical ribbon after 3 min of mixing. Interestingly, the dye remains confined to the upper compartment of the tank (f). The regions with and without dye are segregated from one another in that the exchange of molecules takes place by diffusion. This classical segregation presents challenges in terms of batch mixing processes. If undisturbed, then the dye would eventually diffuse across lamellae to other regions within the vessel. Reducing the vessel dimensions (e.g., 250 mL falsk) helps to decrease the diffusion time described by Equation (1), but it may not eliminate segregation altogether in laminar mixing. Moreover, the time scale for such diffusion could be on the order of a reaction time scale. 
Neal Anderson, in a recent ASAP review from Organic Process Research and Development [2] on continuous processes also has a few things to say about micromixing:
Warning signs may be seen in the laboratory if there is a change in product yield or quality with a change in (a) mixing speed, (b) additions (portionwise or continuous, rapid, or slow), (c) the position of a feed stream, (d) scale-up to a vessel with different geometry, or (e) holding time before workup.
In such cases micromixing, poor heat transfer, or the stability of intermediates or products is the cause. ...If micromixing is an issue, suitable approaches may include increasing the agitation rate, extending the addition time of a key reagent, diluting reagent solutions for the addition, cooling the reaction or adjusting the pH to moderate the reaction, employing an inverse addition, resorting to a less reactive reagent, such as Ac2O instead of AcCl, or using continuous operations. ...Continuous operations, which may require some time initially to set up equipment and find optimal concentrations, temperatures, and flow  rates, may provide the only practical approach.
I am really getting an education in mixing.

[1] Hartman, R.L., McMullen, J.P., Jensen, K.F. "Deciding Whether To Go with the Flow: Evaluating the Merits of Flow Reactors for Synthesis." Angew. Chem. Int. Ed. 2011, 50, 7502-7519.
[2] Anderson, Neal G. "Using Continuous Processes to Increase Production." Org. Process. Res. Dev. 10.1021/op2003347kl

7 comments:

  1. It's all too true that as chemists we often pretend to live in a world believing that chemistry in the lab is uniquely the sanitized uniform reaction we draw in or lab notebooks.

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    1. As synthetic chemists we also pretend to be scientists (diviners of the natural world) rather than engineers (creators of new entities). This way we comfortably forget that numbers with their associated messy properties (accuracy, uncertainty, scalability) are as important as the creations they describe.

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  2. I just wanted to say that Process Wednesdays are what keep me coming back here, among other features. Thanks, and please keep it up!

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    1. O+G chemist -- saw your other comment. How long have you been in your industry?

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    2. I've only been working in O+G for 4 years - still a relative newcomer. The company I work for is relatively small, though, so I'm lucky enough to work with many of our longest-tenured (35+ years) employees and gain some insight into the history of our role in the industry.

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    3. Please e-mail me at chemjobber -at- gmail/dot/com. I'd love to hear more (off-the-record, if you so desire.)

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  3. Beautiful science - it's great to see something I've often taken for granted visualized so spectacularly well.

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