Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: Nescafe on March 17, 2015, 03:01:50 PM
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Hi,
I have worked with two both Hardcore Synthetic chemists and Medicinal Chemists. I consider myself smack in the middle of the two in terms of training.
Usually hardcore synthetic chemists I find to be obsessed with the color of their final product. "Ohh Should be white solid/colorless oil" repurify, recrystalize.... Years go by...
MedChemists are more so focused on getting it into vials and having them tested. If HPLC, NMR etc checks out and there are no evident metals lingering around Pd, Cu, Rh, Ru, move forward sort of an attitude.
I was just curious, at the end of the day, it seems it all depends on what level of testing we are at, preliminary, animals etc.
Just curious to hear some perspectives of other Organic chemists on this forum.
Thanks,
Nescafe.
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What do you mean by "hard core synthetic chemists"? Total synthesis guys? Production chemists?
I think this largely depends on what its going to be used for. If the compound is going into animals (mice->humans), med chemist or otherwise, the compound has to be spotless. Depending on what your last step was, color can indicate an impurity. Since a little color can go a long way, that spot of color might indicate an impurity below the limit of detection for NMR or standard LCMS. In my lab, we have to use LCMS/MS to check for a specific impurity that arrises from the synthesis of our analogues, which at 0.1% is enough to cause massive toxicity at the doses we use in mice of the title compounds.
Another problem can be trace solvent, which another coworker of mine is currently dealing with. The pure compound is a white powder, but with trace solvent levels that are practically undetectable by NMR (murmurs in the baseline) it stays a gummy semi-solid.
If the compound is just for biochemical screening or cellular assays, than good by NMR (proton/carbon) and a high res mass is sufficient to go ahead.
I could see production level chemists easily justifying significant time optimizing the isolation of the final, >99.99% pure compound that will be sold/distributed.
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What do you mean by "hard core synthetic chemists"? Total synthesis guys? Production chemists?
I think this largely depends on what its going to be used for. If the compound is going into animals (mice->humans), med chemist or otherwise, the compound has to be spotless. Depending on what your last step was, color can indicate an impurity. Since a little color can go a long way, that spot of color might indicate an impurity below the limit of detection for NMR or standard LCMS. In my lab, we have to use LCMS/MS to check for a specific impurity that arrises from the synthesis of our analogues, which at 0.1% is enough to cause massive toxicity at the doses we use in mice of the title compounds.
Another problem can be trace solvent, which another coworker of mine is currently dealing with. The pure compound is a white powder, but with trace solvent levels that are practically undetectable by NMR (murmurs in the baseline) it stays a gummy semi-solid.
If the compound is just for biochemical screening or cellular assays, than good by NMR (proton/carbon) and a high res mass is sufficient to go ahead.
I could see production level chemists easily justifying significant time optimizing the isolation of the final, >99.99% pure compound that will be sold/distributed.
Very Good Answer!
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There is a saying "s**t goes in, s**t goes out"
I think if you did the reaction and your product was white solid then when you do it again and your product is yellow then something is wrong.
I agree with TheUnassuming, it depends
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Usually hardcore synthetic chemists I find to be obsessed with the color of their final product. "Ohh Should be white solid/colorless oil" repurify, recrystalize.... Years go by...
Dumb question: If they are synthesizing it for the very first time how do they know it ought to be white when pure?
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I work in Medicinal Chemistry field and I must admit I am usually quite obsessed with the purity of my compounds. I must admit I'm not very experienced but what I like to see is a spotless NMR spectrum. But sometimes I'm willing to strike a compromise especially if faced with a difficult case. Not to let those years go by... :)
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Usually hardcore synthetic chemists I find to be obsessed with the color of their final product. "Ohh Should be white solid/colorless oil" repurify, recrystalize.... Years go by...
Dumb question: If they are synthesizing it for the very first time how do they know it ought to be white when pure?
It is actually not a dumb question as it resulted in some interesting responses. Plus, that was more so a statement rather than a question if you actually paid attention when you were reading it.
Everyone else thanks for your response.
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I think curiouscat was being self deprecating to his own question rather than making a statement about yours.
As far as how do you know if its supposed to be white solid ect. if its the first time for a compound, usually its just logical analogies.
I know a new compound in my current library should be solid because all the others in the class are solid and are structurally (mass, H-bond acceptors/donors ect) similar. I also know they should be white (assuming there isn't increased conjugation or the like) since the other compounds are also white.
If its a completely new compound with no examples near to it in the literature, then you are on your own... but there is almost always a close example in the literature.
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I think curiouscat was being self deprecating to his own question rather than making a statement about yours.
Indeed.
No offense intended Nescafe.
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I know a new compound in my current library should be solid because all the others in the class are solid and are structurally (mass, H-bond acceptors/donors ect) similar. I also know they should be white (assuming there isn't increased conjugation or the like) since the other compounds are also white.
Gotcha. Thanks!
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The real question is if the color is indicative of the purity. In some cases a ppb trace of a compound can color a sample, in other cases a grossly impure sample can be colorless.
So before making a compound for medicinal chemistry, there should be a standard QC protocol, often including NMR, LC-MS, CHN, mp/bp, or other methods, with predefined levels of purity wished to be attained before assaying the compound. But be aware that none of those methods are perfect, as NMR will not detect many non-hydrogen containing solvents or salts, MS cannot see many organics which do not ionize, LC-UV does not see many solvents and non-aromatics, and every analytical method is only so good. But often 95% or better is good enough for simple assays, and then if further tests are to be done, a more detailed prep and analysis are in order.