Organicsynth
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Question about how to scale a synth
Let's suppose this is the synthesis:
While stirring Substance A (0.400 g, 1 mmol), add Substance B (10 mL, 3 mmol) drop wise for 10 min.After the reaction is complete, add Substance C
(0.500 g, 2 mmol) and stir for 20 min.
If I want to get a 10x yield, I just need to multiply every substance weight by 10 and that's it?
Or do I need to make some other calculations?
I know this might seem like a stupid question and if the answer is "yes you just need to 10x everything", yeah it is stupid. Though I just want to be
100% sure about this, because I'm learning chemistry by myself and have no one to ask basic stuff.
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Bedlasky
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Yes, you are correct. Just multiply all by 10.
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morganbw
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You definitely need to use 10X of the reactants but it is very possible that you do not need 10X of whatever solvent you were using.
This varies from synth to synth.
I would want to know the reaction pretty well before I scaled up 10X.
Exo therm can cause problems if you are not on your game.
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Organicsynth
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Ahhh, I always thought it would be like that but I needed to be sure, thanks for the replies guys.
morgan, how it's possible to know if I will not need to 10x my solvent?
Is there any method you can explain me or point me a website to check it?
This is very important, as we should not just scale everything 10x if it's not necessary.
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morganbw
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Quote: Originally posted by Organicsynth  | Ahhh, I always thought it would be like that but I needed to be sure, thanks for the replies guys.
morgan, how it's possible to know if I will not need to 10x my solvent?
Is there any method you can explain me or point me a website to check it?
This is very important, as we should not just scale everything 10x if it's not necessary. |
It definitely does not hurt to scale your solvent up 10x as well. Sometimes that takes very large glassware to accommodate.
I think that experience may be the only answer, or perhaps some experiments to see.
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Organicsynth
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Yeah, it makes sense, with experience and time we can adjust the solvent needed to perform a complete reaction.
I have just a couple more questions, it's about refluxing.
Let's suppose we have 1 g Substance A being refluxed with 50 ml of Substance B for 10 hours.
If I wanted to reflux another 1 g of Substance A, would I need to replace the Substance B for a new 50 ml?
I ask this because refluxes tend to use alot of liquid and just a little solids amount.
I wonder if there's any calculation or method used to know when the refluxing Substance B has been "exhausted".
Another thing I question myself is how it's possible for the chemist to know exactly that he will need 50 ml of Substance B to reflux with 1 g of
Substance A? Why not 20ml instead?
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karlos³
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As for the solvent volume: in your example in the first post, you have 1mmol of substrate, and 10ml of another substance which probably is meant to be
the solvent I guess.
This is for so tiny scales actually needed to be able to manipulate the solution more effectively, i.e. stirring, filtration, rinses etc, all that.
If you would have 400mg substrate and not 10ml but 1ml, you couldn't stir it properly, and when you loose 0,1ml during a filtration and can't wash
everything out, you suddenly lost 10% of your reagents.
Now, lets multiply by ten... 4g of substrate in 100ml.
This is not needed at all, you don't even need half of that volume probably, maybe a quarter of that would still be fine.
It depends on the specific reaction of course, but mostly people don't deal with vigorous and exothermic foam-vulcanoes on a regular schedule.
For most other reactions you can adjust the solvent amount... but there is no rule of thumb!
This is a matter of experience, knowledge and skills, and what applies in some case, don't necessarily does so in another.
With that in mind, I would always try to keep the solvent volume in reasonable amounts and never would I just multiply it with the same numbers as
everything else.
It is not a reagent, keep that in mind, so it only needs to be in adequate amounts that the other reagents are dissolved and thus able to react well
enough.
In some cases, the solvent is a reagent though, or at least some quantity of it is used as a reagent... an example would be the FC-acylation of
benzene with an acid chloride, and of course there are others but I don't have any other example in mind at all 
It will always be very helpful if you run the planned reactio first in a small scale, so you know the course of the reaction already, which allows you
to adjust the solvent volume much more thoughtful and ideal for the demands of the reaction you plan to upscale.
My own experience and opinion, usually only very rarely scaling anything up, is exactly what I described.
Small scales benefit from a good excess of solvent, but as the amount of substrate increases, you decrease the corresponding solvent volume amounts
increasingly more, in relation to each of the starting material quantities, you scale up with, so much that 0,4g/10ml becomes later on much, much
less.
I'll try to describe how that goes in practice.
In detail, 400mg and 10ml solvent as in your example, but now if you double the starting reagent, you only add 1-2ml of solvent for such a portion.
The 10ml at the start are, as said, for better manipulation of the reaction that much larger in relation.
Now with 4g, ten times the reagent, and 25-50ml depending on how temperamental the reaction proceeds, is good enough, now 10x again.
Thats 40g, I would say 250ml is more than enough, maybe you can get away with 150ml just as well.
400g, well 1,2-1,5l is more than enough, maybe 1l already suffices.
And so on.
Your last example, 1g reagent in 50ml...
There is only one reason why so little of that substance are in such a large volume of solvent.
And that is, the substance A being so badly soluble it needs that much... which is not what you asked for of course.
Just want to explain my initial thoughts about this 1g/50ml scenario, this is immediately something I wonder about the reason for.
And additional gram of that substance, i.e. 2g would in case of the large majority of chemicals never need 100ml, I wouldn't even add any additional
solvent... maybe at 10g, I would add 10-20ml so we have instead of 1g/50ml, a much more reasonable 10g/60-70ml, for 20g still less than 100ml, etc.
Of course I am just generalising, which is never doable in practice and in theory it isn't really doable either.
I just do this to visualise how it goes when you upscale a reaction.
You see, the solvent is not participating directly, and thus needs only to be present in amounts sufficient for dissolution and allowing proper
mixing.
So make use of your growing knowledge and experience to be able to use just as much as sufficient, while keeping the quantity as small as possible.
This is important because solvents aren't cheap, at least when you don't keep an eye on a thoughtfully responsible consumption of them.
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Sigmatropic
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I'm with Karlos here, but would like to add that you can generally aim at concentrations of your limiting reagent between 0.1 and 1 molar, typically
between 0.2 and 0.5.
Now whether you work with w/v or molar concentrations is a matter of personal preference except for very large and very small molecules in which case
I would look at molar concentrations.
Do remember that reactions also happen in surries, when not everything is dissolved, just a small portion needs to be dissolved to react and this can
be continually replaced. And to be honest, a reactive crystallization has a certain wow-factor to it :p.
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