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Topic: {Scale up} rules and helpful information  (Read 3023 times)

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Offline foxfourfive

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{Scale up} rules and helpful information
« on: July 01, 2016, 04:47:38 AM »
Hey, when performing a synthesis and significantly up scaling amounts, what rules and special care is needed? Specifically how much solvent should be used etc.

Example:

1 mole of Compound A in a solution of Solvent A is reacted with 1 mole of Compound B in a solution of Solvent B. The resulting yeild (30%) of 30g Product A is extracted with 100ml Ether and dried.

If I was to increase this to product ten times the amount, what would it look like?

{MOD Edit -- better title}
« Last Edit: July 02, 2016, 06:51:15 AM by Arkcon »

Offline Guitarmaniac86

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Re: Upscaling rules and helpful information
« Reply #1 on: July 01, 2016, 05:45:59 AM »
That depends on how large your scale is. I have gone from 1g to 500g scale synthesis (at my industrial sponsor) with no real issues.

Does the reaction produce an exotherm? If so, you will need to cool it before doing your additions otherwise you might get a runaway exotherm that causes your solvent to boil over at best, and cause an explosion at worst.

Only after you are satisfied that any exotherm is no longer a risk should you start heating/warming the reaction, and do it slowly, with constant monitoring of temperature. Have an ice bath ready just in case.

Does the reaction evolve a gas (effervesce)? If so you need adequate venting and add things slowly and think about cooling. Do not add things in at once. Add them in portion wise. This goes for all reactions, whether they evolve gas or exotherm etc.

You can reduce solvent volumes on scale up. Say at 1 g scale you use 25 ml solvent, at 100 g you would think to use 250 ml, but you can get away with 150 mL depending on solubility.

Work up volumes also increase so special care needs to be taken, but again, you can get away with reducing solvent volumes a lot.

Larger glassware can be a bit difficult to work with also so just take care.

I cant think of much more but when I do I will update this post.
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Offline foxfourfive

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Re: Upscaling rules and helpful information
« Reply #2 on: July 02, 2016, 02:04:03 AM »
Thank you! Very informative. Just to confirm did you mean 250mL or 2500mL?

Offline Guitarmaniac86

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Re: Upscaling rules and helpful information
« Reply #3 on: July 02, 2016, 02:49:22 AM »
Sorry yes I should have said 2500 mL as the scale is going up a hundred fold. At these scales you can drop off the solvent volumes a lot.

I have done 100 g reactions in 750 mL before. Didn't want to use 1.5L of DMF.
Don't believe atoms, they make up everything!

Offline Babcock_Hall

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Re: {Scale up} rules and helpful information
« Reply #4 on: July 04, 2016, 10:29:47 AM »
Although it may be simplistic, I find it helpful to remember the square-cube law.  For a spherical flask, the volume of the flask increases proportionally more than surface area does.

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