[gvic]

I'm attempting to accomplish an acetal formation to protect these two hydroxyl groups on the ribose portion of adenosine. Some literature states that reactions such as this using ribose should proceed at room temperature for 3 hours with H2SO4 as the catalyst. I'm wondering what the best way would be to remove the H2SO4 from the acetal protected adenosine once the reaction has been completed. The reaction takes place with acetone as the solvent and removal of the acetone through evaporation leads to an oily residue that I assume is mainly H2SO4 and product.

I was thinking that it might be possible to neutralize the acid with NaOH and then try to seperate the sodium and sulfate salts from the adenosine into an organic solvent. I'm not sure what organic solvent would be best but I think the adenosine should be fairly soluble in hexanes or some other non polar solvent as long as the amine group has assumed a neutral charge after the addition of the base. Perhaps running a column or trying to selectively precipitate the adensoine might be easier. Alternatively I could substitute p-TsOH instead of H2SO4 for the acid if that would be easier to seperate from the protected adenosine.

I'd appreciate input anyone has to share

[Dan]

We do acetonide protections routinely here. First of all, I strongly discourage concentrating the solution without neutralisation - you will end up with your compound in a puddle of conc sulfuric acid, which is rarely a good place for sugars to be, although you might get away with it.

Secondly, the standard procedure is to neutralise with excess (solid) sodium bicarbonate. Depending on the scale this can take a while since the bicarb has a very low solubility in acetone. The sodium sulfate generated precipitates out (and presumably doubles up as a drying agent as well) and can simply be filtered off along with the excess bicarb leaving you with your organics in a neutral acetone solution. Vac down & column/recrystallise.

pTSA is a perfectly good alternative to sulfuric, as is CSA. You can also add some 2,2-dimethoxypropane which can act an an isopropylidene source and a drying agent.

[gvic]

Thanks a lot for the advice. I've repeated the reaction using NaHCO3 to neutralize the solution. I'm performing this reaction with 50mg of adenosine in 50mL of acetone. So far the NaHCO3 is dissolving very slowly and not changing the pH of the solution much so I'm going to leave it overnight and hope it's neutralized tomorrow. I added around 5mL of concentrated H2SO4 which in retrospect I think was way more than necessary .

[Dan]

I added around 5mL of concentrated H2SO4 which in retrospect I think was way more than necessary .

Yeah, that's a ton. We rarely use more than 1% v/v sulfuric acid/acetone, that said you do have an internal basic residue so in your case you might need to hit it a bit harder than if it were just ribose. I assume the very high dilution is due to low solubility of adenosine in acetone?

Tips to speed up the neutralisation are 1. Use a very large excess of bicarb, 2. Efficient and vigorous stirring is vital, 3. You can grind the bicarb to a dust with a mortar and pestle before you add it.

[Rishi]

Well, since your solvent is acetone, would you like to try adding lime to the reaction mixture. I think it will neutralize your sulfuric acid and precipitate the calcium salt leaving a relatively purer product in acetone.

But I would suggest a less volatile solvent for this process.

[Dan]

But I would suggest a less volatile solvent for this process.

Why?

[gvic]

Sorry I forgot to follow up on this topic. I found a good workup in a journal. If anyone's still interested I managed to acheive very high yields by using p-toluenesufonic acid and dry acetone distilled over CaSO₄. Thorough drying of the acetone is key. I neutralized the reaction with a saturated solution of NaHCO₃ and then evaporated the solvent and resuspended it with acetone to recover the product from the salts. I purified with a column though it was hardly necessary, given the purity of the crude product. This reaction was much easier using TsOH as opposed H2SO4 which always left with me with oily products containing large amounts of unreacted adenosine