What is your starting material: acid or acid chloride. ->Is it really necessary to use molecular sieve? Do you use HBr/AcOH for quench of TMS-CH2N2 or the formation of alpha-halogenketone?

http://www.commonorganicchemistry.com/Rxn_Pages/Acid_to_Ester/Acid_to_Ester_TMS-CHN2.htm

Sorry, I should have mentioned that--yes my desired product is an alpha methyl haloketone, R-(CO)CH2Br. Thank you for you answer.

I use the the molecular sieves for both the activation of the carboxylic acid forming an acid chloride in situ and then the subsequent diazotization (i.e., treatment with TMS-CHN2). I found literature precedent for this and I have personally found for my system, when comparing the same reaction with no molecular sieves, I get much better yields. Initially I isolated and purified the diazoketone, but I found that this is not necessary and instead I can simply filter off the molecular sieves and treat the unpurified diazoketone directly with HBr.

Now I am wondering if I even need to filter off the molecular sieves. That is, in a solution containing molecular sieves, I form the acid chloride (20 min), followed by the diazoketone (30 min), and then directly treat this solution with HBr/AcOH in the presence of the sieves.

I don't see any literature precedent for this, but I know one cannot assume molecular sieves are compatible with all materials. For example, molecular sieves and benzyl bromide can be explosive: "Redistilled /benzyl/ bromide was stored over 4A molecular sieve previously activated at 300 deg C. After 8 days the closed bottle burst from internal pressure of hydrogen bromide. This was attributed to the sieve catalyzing a Friedel-Craft type intermolecular condensation-polymerization with liberation of hydrogen bromide." [1] Obvisouly my system is far different than this but I do want to ensure that it is safe to do in my case.

[1]https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?bs+hsdb:@term+@DOCNO+369

Acetic acid is compatible with molecular sieves but Hydrobromic acids not

Thank you so much, Vijay.

May I ask why? Does the Bromide ion simply become trapped in the sieves (4 angstrom), as it is smaller than water? Or is there some sort of safety issue or something related to unintended side reactions as in the case with benzyl bromide?

The obvious thing to do is to add some (activated) sieves to 33% HBr/ AcOH and see what happens. I suspect there will be an observable physical change if the sieves are not compatible.

Without knowing your actual starting compound and the target product I fail to understand why this method is being used as there are other ways of obtaining alpha bromoketones that are more direct and safer.

Jack M Hinkley Yes, I definitely considered just adding HBr soln to the sieves to see if there was some observable change (see last paragraph of my original post), but I was concerned about the safety as there are some materials that are very incompatible with sieves and produce dangerous byproducts.

My starting compounds are Cbz-protected amino acids, (e.g., Cbz-Phe-OH). The most common method is generating CH2N2, but this is extremely toxic and explosive, so I've been using TMS-CHN2 is a somewhat safer alternative (but it's less reactive). Currently I have a 3-step, 1-pot reaction. What other methods did you have in mind that are more direct and safer?

Grant, now that I more details about your synthetic scheme I can see the potential difficulties that certain other routes to your bromomethyl ketone derivatives may have. I presume that you have done the necessary literature search covering the preparation of the desired products and will make no suggestions. It always helps to account for all the reaction products in the reaction scheme. As far as the sieves are concerned I don't see a problem as they are inorganic zeolites (see the molecular sieve entry in Fieser and Fieser Vol 1) so adding HBr/AcOH should be a nonissue, but it is a good idea to check. What is the reaction solvent?