[AllylicAzideUMN]

Hello everyone,

My research involves the optimization of organic reactions. Oftentimes, this means I need to set up screens to systematically investigate the effect of different reaction conditions on the reaction's efficiency. In order to compare the individual reactions in my screens, I want to include an internal standard so that the data I obtain from NMR and GC analysis are most reliable. However, I am not sure when is the best time to add the internal standard to the system.

Is it best to add the internal standard with the other reagents at the beginning of the reaction, and possibly risk the ratio of starting material and standard changing during work up? Or is it best to add the standard at some point after the work up? Some of my reactions are worked up by removing the solvent and adding a new solvent for analysis (e.g. CDCl₃) while others involve a liquid-liquid extraction before analysis. Would the nature of reaction work up affect how I should approach using an internal standard?   

Thank you so much in advance for the advice!

[hypervalent_iodine]

What information are you hoping to obtain by having a standard? If this is for quantitative analysis, then is it not better to simply include the standard in the sample prep?

[AllylicAzideUMN]

I am trying to monitor conversion of starting material to product. Previously, in the absence of a standard, I have used the ratio of remaining starting material to product as a gauge of conversion. However, given that both the amount of SM and product change in the reaction, it would be better to compare the ratios of SM and product to an internal standard whose amount never changes, correct?

[hypervalent_iodine]

I am trying to monitor conversion of starting material to product. Previously, in the absence of a standard, I have used the ratio of remaining starting material to product as a gauge of conversion. However, given that both the amount of SM and product change in the reaction, it would be better to compare the ratios of SM and product to an internal standard whose amount never changes, correct?

I'm not sure that you would need a standard in that case. If you know the mass of what you're getting out, then you would have an idea of mass recovery, and conversion you would get by using the relative peak areas of your SM and product. I don't think using an internal standard is going to give you any additional useful information, but perhaps someone else can correct me on that if I've missed something.

I would be reluctant to use an internal standard for GC anyway. If you really wanted to go down that route, I think it would be better to generate a standard curve using a pure sample of your SM and product and then relate that to the peak areas you are getting from your reactions. Accurate sample prep is obviously very important here.