[bstanley]

Hi all,

I would like to request some help for an organic synthesis. I'm trying to do a ketalization of glycerol. I attach the product that I wish to synthesize. According to D. A. Jaeger, J. Am. Chem. Soc. 1989, 111, 3001-3006:

(1) Mix the 55.7 mmol of the ketone with 60.0 mmol of glycerol and 100 mg of p-toluenesulfonate monohydrate (catalyst) in 500 mL of benzene. Reflux for 45 hours under a Dean-Stark trap fitted with a drying tube (calcium chloride).

(2) Reaction mixture is washed with 500 mL 5% sodium bicarbonate.

(3) Dried with sodium sulphate and rotary evaporated.

I have tried this reaction for 3 times now and I failed to get any solid product at all. The only difference is I used difference ketone than the one used in the paper. I used 2-tridecanone which is a ketone with shorter chain. After I rotovap the benzene layer, I don't get any solid product. All I get is white oily looking liquid mixed with the benzene. I have a few questions:

(1) What is the purpose of washing the reaction mixture with 5% sodium bicarbonate?

(2) When they say "washed", I assume the reaction mixture is mixed with the 5% sodium bicarbonate in a separatory funnel and the organic layer is collected. Is this right? Or am I supposed to collect the aqueous layer? But that doesn't make sense because the next step is to dry it using sodium sulphate.

(3) I'm puzzled by the lack of any solid. I mean, I should still get the starting material back, right?

(4) When I rotovaporated the organic layer, I didn't rotovap it to dryness. I just rotovap it from approximately 400 mL down to 30 - 50 mL. Should I rotovap it to dryness?

I'm at the end of my rope here and I'm not sure what I did wrong. So, any advice will be greatly appreciated.

Cheers,

Stanley

[tmartin]

The point of washing with the 5% sodium bicarbonate is to neutralize the acid catalyst you used in the reaction.  You would put the two layers in a sep. funnel, and keep the organic layer.  Drying with sodium sulfate afterword (or washing the organic layer with brine)  just helps remove residual water.

Is the product supposed to be a solid (sorry, I did not read the paper you linked)?  I'm guessing once you rotovap down to 30-50 mL you take an NMR and look for your desired product and see none?  How do you monitor the reaction?  If the reaction does not go to completion, I imagine the glycerol is going to go into the water layer, so if you do not keep the aqueous wash you will not recover that SM, and if you only have the starting ketone, I imagine it would be pretty volatile, and could be lost when you rotovap away the solvent, especially if it's benzene (how high are you heating while rotovap-ing?).  Your desired product also has a MW of 272, is it possible you are losing it during rotovap-ing?  I'm not sure that it would be a volatile compound, perhaps someone else would have insights, but I guess it could be possible, especially if you are removing benzene under vacuum at an elevated temperature.

[bstanley]

Hi there,

Thank you for the reply. Yes, the product is supposed to be solid. No, I haven't run it through the NMR. I did notice that the solution is clear at the start of rotovap and it turned brown at the end of the rotovap period (40 - 50 mL). I also notice an increase in the viscosity of the solution after rotovaping. You are right, I think I will try to run an NMR of the solution and see if my product is there. I rotovap it at 65 centigrade so I highly doubt the 2-tridecanone (starting material) evaporate off. I still keep the aqueous wash, but I'm not interested in the glycerol. I mean, it is pretty cheap. Anyway, thank's again for your insight.

[tmartin]

If the solution is turning brown, I would assume something is definitely in there.  It may be possible that solids will form once your completely remove the benzene.  They may not be the nice white solids, but perhaps upon purification (column chromatography or recrystallization) you would obtain the desired white solid.  As for the starting material, I really only was implying you could check for glycerol in the aqueous layer just so you know if you should expect 100% conversion, or less if you recover some... although I do admit it is a pain to fish out cheap SM from the aqueous layer.

[Neecze]

I did some time ago acetal form glycerol and benzaldehyde. I think it's important to have anhydrous glycerol.

Your reaction system (i mean glycerol/benezne/ketone) should be biphasic. If you noticed that droplets of glycerine disappeared during reaction it would mean reaction worked. Then, work-up could be a problem.

[bstanley]

Hi,

Thank's again for all the replies. One thing that puzzles me though is how slow the benzene evaporated when it was down to 40 - 50 mL. The first 400 mL evaporated easily in 60 centigrade rotovap, but the last 40 - 50 mL hardly evaporated even after 20 minutes of rotovaping in 70 centigrade. Is this normal? Thank's.

[OC pro]

Anhydrous gylercol can not be obtained. Additionally its nonsense to use anhydrous material. Water will be removed with the Dean-Stark.
From where do you have the information that your compound is a solid? I suppose it is liquid.

http://www.orgsyn.org/orgsyn/default.asp?formgroup=basenpe_form_group&dataaction=db&dbname=orgsyn

This is the procedure using acetone for ketalization. The product is an oil.

Additionally: I think you still have unreacted ketone in the mixture. The boiling point is quite high (134.00 °C. @ 10.00 mm Hg).

Seems you have to distill the mixture under a very good vacuum. (<1mbar)

[bstanley]

Hmmm....now that I think about it, my product has a much shorter alkyl chain than the one in the paper. Man, this is going to be a problem because I need the compound to do another synthesis. How am I supposed to separate them? A separatory funnel? Sorry, I'm not an organic chemist, so I am slow

[orgopete]

Well, you haven't proven whether the reaction worked or not. Did you collect the theoretical amount of water in your Dean-Stark trap? Carbonyl absent in IR?

Your product is going to be an oil as it will be a mixture of stereoisomers.

It is interesting to me that while I worked in industry, we were not allowed to purchase or use benzene in any of our ordinary lab settings. You needed special conditions to work with a class carcinogen. I always used toluene or dichloroethane for most substitutions.

[fawad0418]

I think best way is to dilute the rest 40-50 ml solution with diethylether (say 250-350 ml)...then wash with brine (satd.NaCl soln. 3 times), dry over Na2SO4 and then evaporate (say starting from 730mbar to 200mbar @40 degrees)...i hope u wud b able to separate your clean product.

[OC pro]

I think best way is to dilute the rest 40-50 ml solution with diethylether (say 250-350 ml)...then wash with brine (satd.NaCl soln. 3 times), dry over Na2SO4 and then evaporate (say starting from 730mbar to 200mbar @40 degrees)...i hope u wud b able to separate your clean product.

For which reason? He already did aqeuous work-up.
Vacuum distillation of the residue is the purification of choice.

[bstanley]

Hi,

Thank you for all the replies. I run an IR on the raw product (residual oil form) and there is a carbonyl peak present which indicates the presence of the starting ketone (2-tridecanone). I ran the raw products through flash column chromatography (silica gel) with 1:6 (ethyl acetate : hexane). The IR of the purified product indicate that it is free of starting material. So things are working. Thank you again for all the reply.

Bob