Risk assessments of nitrosamine in two-phase systems

Hi all,

I have a question, does anyone have any literature suggestions on the formation of nitrosamines in two-phase systems?

We have a case where the only step for the formation of nitrosamines occurs in a phase separation between toluene and acid solution, but the secondary amine (tertiary amine impurity) is mostly found in toluene. I would like to understand the training risk in this case.

I appreciate the colaboration of everyone.

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Hi There, interesting topic indeed. Just a few starting thoughts:

Do you know the potential sources of nitrosating species, in which phase they would be located and the approximate concentration in the respective phase?
Have you got any data for concentration of your secondary amine and tertiary amine impurities in your phases?
The other aspect to look into could be surface contact area (driven by mixing in particular) and time of contact ?
Those aspects could be good starting points to build your process understanding and potentially branch out to use existing kinetics models in aqueous system (see Org.Process Res. Dev. 202, 24, 9, 1629-1646 for example of kinetic model)?

I hope this is useful, welcome other thoughts.

kind regards

It should also be borne in mind that the reaction does not necessarily occur interphase, and nitrosation can also occur on tertiary amine. It is worth measuring the concentration of amines in the aqueous and organic phases. Besides, it is also worth (as my previous speaker wrote) to know what is the actual nitrosing agent and whether it is hydrophilic (e.g. Nitrite) or lipophilic like alkyl nitrites.

Acetic acid is an ideal environment for nitrosation (optimal pH~3) if you have such possibility, I would recommend adding a small amount of ascorbic acid to the aqueous layer before introducing amine, this should help to reduce nitrites.

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