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CHLOROEPHEDRINE is best synthesized with (ZnCl2 + con.HCl) or (CaCl2 + con.HCl) + EPHEDRINE

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Thats plain not true. 70% to 76% yields are shit. There are better ways - but the reagents are not easy to get.

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EPHEDRINE FREEBASE in ether with THIONYL CHLORIDE (SOCl2), DOES NOT WORK WELL, AS EPHEDRINE HCl IS PRECIPITATED OUT.

IT DOES WORK WELL WITH C6H5-(CHOH)-CH(NO2)-CH3, GIVING 95 - 97% YIELD.

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This makes no sense to me. Ether is plain the wrong solvent - chloroform is the solvent of choice and results in 95%+  yields of chloroephedrine if thionylchloride is used, if PCl5 is used 99%+ are achieved.

So the BEST way is PCl5 in chloroform.
Second is thionylachloride in chloroform.
Before wasting precursor I would advise to go for bromination - ZnCl2/HCl is a poor chlorination agent for ephedrine.
Btw. bromination might be the best choice anyways. Worth a look or two.

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Then after a while not able to get ether I switched to acetone....well the chloroephedrine still came out but my loss was also increased to 20-25%  and I always noticed a recidual brown oily material at the botoom of my acetone that had been used to wash .....that was probably  chloroephedrine free base?

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Acetone is not a good choice of solvent with thionyl chloride? Why you ask? It contains water and 2-propanol. These will react with thionyl chloride. Most acetone (tech grade) contains some water and 2-propanol. Only AR grade acetone will have trace amounts of water and 2-propanol.

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One more question what are the yields in the CaCl2 reflux method to chlorinate ephedrine....and is the product is chloroephedrine free base or chloroephedrine Hcl

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The CaCl2 + HCl method is not as powerful chlorination reagent as thionyl chloride. Yields with this can be 57-60% chloroephedrine free base.

Long reluxing and mechanical stirring help chlorination.
Ref: Modified procedure, Exp. 5.51, pg 557 Vogel 5th Ed.

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via chloroform + thionyl chloride, chloroephedrine is the Hcl variety. So if I basify it with 20% dil NaOH and wash with toluene...I would then have my base that can be hydrogenated in methanol with Pd10% would my product be Meth base , hence needing to gas it to get the HCl salt

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Yes! However, some KOH in the methanol/10% Pd-C will help with the dechlorination of the chloroephedrine.

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.......a tertiary alcohol reacts immediately with the Lucas Reagent , and a secondary alcohol reacts within five minutes ; a primary alcohol does not react appreciably at room

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Yes, your correct Java. I apologize for this error; tired and multi-tasking at the time I think?


So it's while true that the Lucas Reagent on Benzyl alcohols, which Ephedrine, Pseudoephedrine and phenylpropanolamide, react as fast as tertiary alcohols , in general primary alcohols react the least or not at all in this test for alcohols.

Just heat the primary alcohols (eg. benzyl alcohol) with the lucas reagent in hot water and this will accelerate the reaction rate. It however, doesn't mean you will get quantitative yeilds of the desired product.

had a question prior to reading this which was the possibility of using this test to chlorinate a primary aromatic alcohol, namely not protected R-Phenylalaninol. I now see that is not possible and   thionyl chloride and the different Phosphorous acids are not an option for me , for lack of acsses, hence must find a substitute.

If your trying to make benzyl chloride via benzyl alcohol and lucas reagent, then try heating the reaction mixure first, as stated above, before you try to get another chlorination reagent?

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CHLOROEPHEDRINE is best synthesized
 with (ZnCl2 + con.HCl) or (CaCl2 + con.HCl) + EPHEDRINE



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Thats plain not true. 70% to 76% yields are shit.
There are better ways - but the reagents are not easy to get.

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<sup>In my experience, if the materials
are treated in a microwave, rather than reflux,
the matter
can be accomplished in 3 minutes or so. 

I wish i could attest to the yield, but cannot with
any accuracy.  However, I believe it was higher,
based on the quality of the material
formed in the succeeding step.

The pseudo, ZnCl2, and HCl were placed in a device
similar to a small filter flask,
and the exhaust port was plumbed
out of the microwave cavity
using latex hose and glass tubing.

(This was not what ws used, but it was similar..)

Note that synthetic rubber stoppers
and vinyl hose have a short life time
in microwave environments..

the exhaust thru the hole in the cavity sidewall
 connected to an aspirator.
The aspirator suction was modulated
so that it collected the fumes,
but did not reduce the pressure a lot. 

The material is microwaved intermitantly
with your finger on the on-off (door switch..)
until near dry.

Do not attempt this
unless you install a vacuum fume port
or you will lose your microwave to HCl fumes.

Guaranteed.</sup>

<<on 3rd microwave

_{note: I speculate that the microwave
may "over concentrate" the reagents as compared to
reflux because of the selective heating and evap. of
the water??  This is in addition to the "activation"
of the alcohol modality directly....}

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This study of the chlorination of alcohols by Clark and Streight, from Transactions of the Royal Society of Canada 23 Section III, pp 77-89 (1929) states that the best yields for the chlorination of benzyl alcohol aren't when heating is used, but quantitative yields can bee achieved in the cold, using a ratio of 1 BzOH / 2 ZnCl2 / 2 HCl

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....as noted in Post 523897 (lugh: "Chlorination Methods", Stimulants)