Sciencemadness Discussion Board

crystallization and dry reagents

nightflight - 6-12-2006 at 13:46

just out of interest; when titrating from a nonpolar into a polar solvent, i.e. one would like to make a hcl-salt from an alkaloid, (-the np needs to be dry and the polar i.e. aceton needs to be dry-ok), how can there be crystals falling out into the polar solution, when there has been 37% hcl added to titrate?

Shouldn´t the salt dissolve in the water of the hcl aeq. and only crystallize when evaporated? I´ve seen a depicted document, in which it shows the crystals to form in the polar solution, to which the 37%hcl was added.

unionised - 7-12-2006 at 12:08

A lot of hydrochloride salts are much less soluble in hydrochloric acid than in water. Look up the "common ion effect". (Come to think of it, NaCl is a lot less soluble in HCl(aq) than in water.

cbfull - 9-12-2006 at 00:20

If you are sure that they are talking about 37% aqueous, then I don't know how to answer. But most of the HCl precipitations I have ever heard of involve dry HCl gas dissolved in cold anhydrous ether to concentrations up to about 30% or more, as long as the ether is very dry it can be stored for a reasonably long time.

Another solvent is ethyl or isopropyl alcohol. These will hold HCl without reacting as long as they are dry as well. The solution is then added to the alkaloid dissolved in dry ether or even dry acetone in high concentrations.

The key is to keep water out of the solvents because it
1) greatly decreases the solubility of alkaloid in the solvent
2) causes side reactions with the HCl.

nightflight - 19-12-2006 at 05:58

cbfull, you´re right. A calculation of the molar raios showed me that hcl-gas was meant, but not clearly indicated and the third figure behind the comma was off, too.

turd - 19-12-2006 at 07:21

*shrug*
I often prepare HCl salts by dissolving the base in n-PrOH, adding a small excess of 33% HCl and chilling. The yield may not be quantitative, but honestly, who cares. Of course it all depends on the compound to be crystallised.

nightflight - 21-12-2006 at 04:21

Quote:
Originally posted by turd
*shrug*
I often prepare HCl salts by dissolving the base in n-PrOH, adding a small excess of 33% HCl and chilling. The yield may not be quantitative, but honestly, who cares. Of course it all depends on the compound to be crystallised.

this method of chilled alcihol/hcl and solvent seems to be convenient in most (re)crystallisations, performed in a lab.

So I´ve found this article on this topic in the chemsitry archive on Rhodium:
Quote:

Preparation of Ephedrine HCl by Fractional Crystallization

The crude base obtained as above was taken up with about twice its weight of alcohol and neutralized with concentrated HCl diluted with twice its volume of alcohol. Nearly pure ephedrine hydrochloride crystallized out on standing. After filtering it was washed with a mixture of alcohol and ether, and then with pure ether, and dried. A further quantity of ephedrine hydrochloride may be got by concentrating the mother liquors and washings. The final mother liquor was kept for the isolation of pseudoephedrine (see below).

Ephedrine hydrochloride crystallized out from alcohol in prismatic needles, mp 216°C, [α]D22 -32.5° (see Fig. 1).

The salts prepared by fractional crystallization show no change in the melting point when recrystallized seven times. In many of our experiments the salts were recrystallized twelve times.



Recrystallizing 12 times seems to me, as if the experemintators were binging.:D

[Edited on 21-12-2006 by nightflight]

cbfull - 31-12-2006 at 02:19

I think there are two very different types of HCl crystallization being discussed here in the same context so I will specify.

When converting a free base oil to a hydrochloride salt, to maintain high purity standards it would be wise to use all dry solvents, including the HCl solution (like 25% in 2-propanol). Side reactions are greatly reduced and the crystal formation is pretty much quantitative, not to mention very clean.

The other topic seems to be re-crystallization by simply dissolving the salt in some system of solvents and either cooling below saturation or adding lots of the solvent it is less soluble in. In my experience this technique takes time and control equipment to reach any reasonably high purity.

As for the former, in these very dry solvents the crystals tend to join as little particles rather than form large lattices, this benefits purity by trapping less dirt and allowing it pass through during collection.