alternative to Diethyl Ether

[barnabe]

Hi,

I make a pyridine salt which contains the pyridine and an organic weak acid. The standard procedure to isolate the acid and remove the pyridine is to dissolve the salt in Diethyl ether with HCL, and let the diethy ether evaporate, which leaves the organic acid crystals with purity 99%.

But i would like to use something else, less flammable than ether to isolate the said acid.
Do you have any idea what could be used?
The acid is composed of C H O and is completely insolube in water. It is mildy soluble in alcohols and quite soluble in dichloromethane.

Thanks for any motivated suggestion.

Regards

[hypervalent_iodine]

I'm not sure why you're so hesitant about ether? As long as you're not lighting fires near it and you're working in a fume hood, you won't have a problem with the flammability. Unless you have some really compelling reason not to use ether, I would just stick with that.

[Knumbnuts]

What happens to the pyridine? You have not removed that by this procedure so how do you obtain 99% purity?

[hypervalent_iodine]

What happens to the pyridine? You have not removed that by this procedure so how do you obtain 99% purity?

 

 

I had assumed that the ether/HCl was a wash step. The HCl would remove the the pyridine.

[Knumbnuts]

He said "dissolve in ether/HCl and then evaporate the ether", so I assumed that there was no wash involved.

[hypervalent_iodine]

He said "dissolve in ether/HCl and then evaporate the ether", so I assumed that there was no wash involved.

 

 

It would either be wash step or the OP is precipitating the compound into the aq. HCl and filtering. I would think a wash would be more effective and simpler to deal with, but in either case, the pyridine would form the HCl salt and not be much of a problem in the way you described. I guess we shall never know until the OP comes back to enlighten us.

 

Edit: I assume this because the way it is written seems to me to be more the victim of poor wording rather than bad chemistry (since it is supposedly from a literature source) and doing exactly what is written in the OP, you are right, would make no sense (though not for the reason you have stated).

[barnabe]

Hi,

thanks for your responses. To clarify the process:

 

The pyridine salt is dissolved in ether and shaken with aqeuous HCl. The ether solution is then washed with water , dried and evaporated to give the compound.


As said, i d rather use another solvent than ether (no fume hood in my settings).
Any idea?
Thanks

[hypervalent_iodine]

Any organic solvent is going to pose problems if you don't have a fume hood.

 

I'm curious though, what exactly is it that you're making?

[barnabe]

hi,

i am isolating an organic molecule from a fruit. It is itself a trivial, non hazardous coumpound. i ll see if i can add the hood.

 

But Would you think of a possible alternative to ether in those setting and properties (slightly acidic coumpound, insoluble in water, but soluble in toluene and DCM)?

at least less flammable and volatile?

 

thanks

[Knumbnuts]

Ether may give a better separation of some of the impurities. Dichloromethane may well dissolve them where ether won't.

You could use diisopropyl ether instead of diethyl ether.

But I am still curious as to your procedure for pyridine removal. Are you filtering and washing the solid, as was suggested?

[hypervalent_iodine]

I would definitely see if you can find a hood to work in. Any solvent you use will be fairly volatile and not something you want to be inhaling for extended periods. Toluene or DCM would work fine and are not as volatile, though the former is still very flammable and the latter is a bit toxic (be wary of getting it on your gloves). Pet spirits (n-hexanes) might also work and would not be as bad as ether (though still quite volatile and flammable).

Ether may give a better separation of some of the impurities. Dichloromethane may well dissolve them where ether won't.

You could use diisopropyl ether instead of diethyl ether.

But I am still curious as to your procedure for pyridine removal. Are you filtering and washing the solid, as was suggested?

 

 

Post #7 looks like a liquid-liquid extraction in a sep funnel.

[barnabe]

Thanks for the 2 last answers.

 

That step i described is litterature. I have not performed it yet. So i can not be more explanatory without extrapolating. Those are the exact terms.

 

It is not specified if the washing is done with separatory funnel or not.

 

I asssume The HCL-Pyridine is washed with water in aqueous form from the ether solution.

 

After checking, Fume hood will be a bit complicated in terms of time/logistics to get. So i m still interested in alternatives to ether. I ll check with the solvents proposed.

The objective is again to remove newly formed pyridine HCL salt (solid or not) from the solutionto get only the compound in the solvent.

 

Regards

@hypervalent_iodine

 

regarding inhalation: i m using active coal masks. IS it protective enough?

It seems i have to find a solvent in which pyridine salt is soluble, pyridine hydrochloric is insoluble, like ether, and in wich aqueous HCL is soluble to some extent (comparable to ether), like ether again. Those 3 properties.

and washable with water

[hypervalent_iodine]

Usually a protocol won't specify the sep funnel as it's a given. Judging by this:

 

 

The pyridine salt is dissolved in ether and shaken with aqeuous HCl. The ether solution is then washed with water , dried and evaporated to give the compound.

 

In general, when it says that a solution is washed as it is here, it means you are doing a liquid-liquid extraction in a separatory funnel. The idea is that you want your impurity (the salt) to be dissolved in a different layer to your product. By performing this in a sep funnel, you can easily remove the initial HCl layer from the organic layer and then remove any trace impurities by putting the organic layer back into the funnel, shaking it with a little more water and once again separating the layers. It will probably have this in the protocol, but also make sure to remove any excess water from your combined organic fractions by adding some magnesium or sodium sulphate and then filtering to remove.

 

There are a lot of YouTube videos on this if you are not familiar with it.

 

Also, if a fumehood is too hard to come by, you will want to at least find somewhere with very good ventilation. I agree ether is probably not the best if a fumehood is not possible, so maybe try toluene. Fair warning though, toluene can take a bit to remove (bp is over 100^oC). Do you have access to a rotary evaporator or some kind of vacuum manifold? I would try not to heat your solution to remove the solvent if you are not absolutely sure your compound is heat stable, either, so vacuum is probably your best bet if you use toluene.

[barnabe]

Hi, thanks hypervalent_iodine for your insights.

 

I do have a rotavap with vacuum. Just not the fume hood. I have to check if the compound can withstand such heat. would you have any othe solvent with lower boiling point and making it easy to wash the HCL layer with water?

 

regards

[hypervalent_iodine]

Ethyl acetate might work, depending on your compound's solubility. You can easily remove it with a rot evap, though you'll likely find that a few traces of solvent remain and that being the case, you'll need a high vac to remove the last of it.

[barnabe]

thanks. i have found NO data about solubility in ethyl acetate, but i have plenty so i can try incrementally to dissolve the compound in it to figure that out and check until some solid crytals are floating. Tha twould be a simple way to go right?

 

thx

[hypervalent_iodine]

Well, if it isn't soluble or you find you get not much back, there's nothing stopping you from re-extracting the aqueous phase with a different solvent.

[barnabe]

sorry but i m not sure i get what you mean. The aqueous phase washes the pyridine hydrochloride. Plus the compound is totally insoluble in the aqueous phase.

 

But i ll test the solubility of the compunds in ethyl acetate.

 

regards

[barnabe]

Hi Again,

 

i got this idea, please tell me your opinion. It is simply the use of Dichloromethane as replacement of ether

 

Pyridine Hydrochloride is insoluble in DCM just like ether. The washing with water might be even easier than with ether as solubility of DCM in water is lower than that of ether.

Also, my compound is soluble to good ratio in DCM.

 

It remains to see (calculate) if HCL can dissolve in enough quantity for the molar ratio of pyridine in the intial DCM.

 

DCM would be ideal in terms of evaporation/flammability

 

Thanks for your opinion.

as to the pending question of aqueous HCL in DCM

 

in the protocol i have with ether it s like this: the pyridine salt (formed with the organic compund) 0.8 g is dissolved in ether 50 mL and shaken with aqeuous HCl (1N, 50 mL) 1 h

 

So, I m not sure as to the quantity needed if ether replaced by DCM. Since water is like more than 3 times less soluble in DCM than ether, maybe i should use 3 times more DCM in the above procedure..?

[hypervalent_iodine]

DCM is a wonderful solvent and very easy to remove. I used to use it quite frequently for extracting and purifying nitrogenous compounds. If it's specs suit you, then sure, go ahead. As I said before, be wary of getting it on your skin and change your gloves straight away if you get any on them. It will go through your gloves quite quickly and start to burn you; it doesn't hurt, but it is irritating and DCM is fairly toxic.

 

 

You would substitute the ether for the same volume of DCM (so, 50 mL if you use 0.8 g of the salt).

[barnabe]

Hi hypervalent_iodine,

 

thanks a lot for your response. You seem to implicitly approbate the deductions i made above (?) regarding the suitability/"substitutability" based on the specs/protocol I gave. ( i understand one can only gives a position based on those parameters)

 

That would be great in effect to replace with DCM wich i already use and is in effect really practical.

 

If i can use same amount of DCM as ether, i understand from that that their difference in water solubility is not an important parameter for the formation of the pyridinium hydrochlorate: the latter will form from aqueous HCL in emulsive way (shaking) rather than solution way...(?)

 

thanks

[hypervalent_iodine]

Shaking should definitely be enough, though to make extra sure you've gotten rid of the pyridine.HCl, I would wash the DCM layer a few times with fresh HCl.

[barnabe]

great stuffs. Thanks for the support.

Last question if i may, a bit unrelated. To your knowledge, do emulsive droplets of a solvent (like DCM) render the evaporation of that solvent harder/longer? do the trapped micro droplets of a solvent affect its evaporation?

 

regards

[hypervalent_iodine]

I'm not sure I understand your questions, so I apologise if I'm off track. Trapped solvent can prevent your compound from crystallising out, but in my experience, DCM doesn't suffer too much from this. EtOAc can be problematic in this sense as it can hydrogen bond to your compound (depending on what your compound is), making it rather difficult to remove (especially if your compound is heat sensitive).

[barnabe]

Sorry if was not clear: I meant the evaporation of DCM in aqueous emulsion. Say i have a ratio of 1 to 4 or 5 DCM to water, emulsified and sonicated with the compound and a protein. I wonder if all DCM contained in droplets can easily escape or can resist evaporation due to droplet entrapment..

I understand one can t say about bonding phenomena without knowing the organic compound or the protein.. But i mean simply the droplet state of DCM and its influence on evaporation..

 

thanks