bobot (Stranger)
05-28-03 05:06
No 435993
      NiCL2     

I have a few questions and you poeple I think will have the answers. NiCL2 dissolved in HCL acid mixed with alcohol,then add zinc dust can this be used as reducing agent? Can NiCL2 be used reduce ephedrine? Is psuedo ephedrine L-psuedo or D-psuedo ?
 
 
 
 
    WizardX
(Wizard Master)
05-28-03 05:15
No 435996
      Lucas Reagent
(Rated as: excellent)
    

NiCl2 + Concentrated HCl produces a powerful chlorinating reagent call the Lucas Reagent.

If you reduce the NiCl2 with Zn dust you get an activated Ni Catalyst.


SYNTHESIS OF HALO-EPHEDRINE

CHLOROEPHEDRINE is best synthesized with (ZnCl2 + con.HCl) or (CaCl2 + con.HCl) + EPHEDRINE ==>> C6H5-(CHCl)-CH(NHCH3)-CH3

PROCEDURE 1 : Arrange a 250 ml round-bottom with a reflux condenser, the top is connected to a device or absorbing excess HCl. Place 68 grams (0.5 mole) of anhydrous zinc chloride (ZnCl2), 50 mls of concentrated HCl, and 50.43 grams (0.25 mole) of EPHEDRINE HCl. Reflux the mixture gently for 2 hours.


PROCEDURE 2 : Arrange a 1000 ml round-bottom with a reflux condenser, the top is connected to a device or absorbing excess HCl. Place 80 grams of anhydrous calcium chloride (CaCl2), 250 mls of concentrated HCl, and 100.9 (101) grams (0.5 mole) of EPHEDRINE HCl. Heat the mixture gently for 10 hours on a boiling water bath.

In both PROCEDURE 1 and PROCEDURE 2, basify the reaction mixture with 20 % sodium hydroxide solution.

The libertated freebase CHLOROEPHEDRINE which seperates is solvent extracted with two, 75 - 100 ml ether (or toluene) portions and the ether/CHLOROEPHEDRINE solution is washed with 2 x 50 mls of distilled water.
The solvent is removed to give CHLOROEPHEDRINE FREEBASE in 70 - 76% yield.


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.
 
 
 
 
    bobot
05-28-03 21:40
      Is psuedo-ephedrine,L psuedo-ephedrine or D...
(Rated as: UTFSE!)
    
 
 
 
    Chewbacca
07-27-03 12:23
      OTC
(Rated as: UTFSE!)
    
 
 
 
    ragnaroekk
(Hive Bee)
07-27-03 14:57
No 450150
      Emde ?     


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



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


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.



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.


Honi soit qui mal y pense
 
 
 
 
    WizardX
(Wizard Master)
07-28-03 07:01
No 450304
      CHLOROEPHEDRINE     

Using chloroform as the solvent.

EPHEDRINE.HCl + THIONYL CHLORIDE (SOCl2) ==> CHLOROEPHEDRINE

EPHEDRINE.HCl + PHOSPHORUS PENTACHLORIDE(PCl5) ==> CHLOROEPHEDRINE

EPHEDRINE.HCl can ONLY be used in chloroform. Ephedrine freebase is not soluble in chloroform, but in ether or benzene.
 
 
 
 
    java
(Hive Bee)
12-09-03 02:10
No 475527
      Re: chlorination of ephedrine     

WizardX   I have a question....so in the chlorination of ephedrine, pseudo-ephedrine...with thionyl chloride once the reaction has occured and the solution looks honey brown , I used to precipitate the chloroephedrine with ether and wash it until white , free of things that might poison the catalyst. 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?  then had I saved it and hydrogenated it it would have given me meth free base?  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........java

We're  all in this world together,
http://www.aztlan.net
 
 
 
 
    WizardX
(Wizard Master)
12-09-03 03:31
No 475545
      CaCl2     


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?




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.


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




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.

 
 
 
 
    java
(Hive Bee)
12-10-03 02:39
No 475806
      Re: Chloroephedrine chemistry     

WizardX,...thanks for the info on the acetone, so would it be true to say that the product, 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......does that sound about right?.......this would save me doing the acetone wash and reduce my loss.....java

We're  all in this world together,
http://www.aztlan.net
 
 
 
 
    Organikum
(Horrible Personality)
12-10-03 12:33
No 475910
      a guess     

Referring to some old halogenation posts (by Psychokitty, Elementary hmmm ?) I guess that there is a possibility to do an chlorination of the ephedrine by in situ formed PCl5 in VERY good yields.

Suggested procedure:
(Pseudo)ephedrine.HCl is dispersed in chloroform and chlorine is bubbled slowly into the reaction. To the reaction some red phosphorous is added (catalytic amounts - also raw matchbook shavings have been told to work fine!) and strong stirring is applied whilst heating the reaction.

Chlorine, Cl2: bleaching powder + HCl, wash through water, dry by H2SO4.
(eh, careful, chlorine was the first deadly wargas of WWI.....)

- make yourself an philosophers stone - make lead to gold - get all girls you want -
 
 
 
 
    java
(Hive Bee)
12-11-03 20:41
No 476210
      Re: Lucas reagent.....     

WizardX...would this Lucas reagent,chlorinating agent, also work on primary alcohols and would it react if the alcohol happens to have an amine group somewhere on the carbon skeleton?....java

We're  all in this world together,
http://www.aztlan.net
 
 
 
 
    WizardX
(Wizard Master)
12-12-03 02:58
No 476275
      Lucas reagent     

The Lucas reagent is used as a test for alcohol groups. ie. primary alcohol, secondary alcohol, tertiary alcohol.

primary alcohol > secondary alcohol > tertiary alcohol

Primary alcohols are more reactive towards the Lucas reagent. Secondary alcohols take longer time to chlorinate (very slow), and tertiary alcohols need heating with the Lucas reagent.


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




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

 
 
 
 
    java
(Hive Bee)
07-30-04 17:30
No 522718
      NiCl2 as a chlorinating agent......     

WizardX....I know it's just an oversight in your behalf but for the benefit of up coming bee's such as myself I wish to clarify your interpretation of the lucas Test.

.......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 temperature. As we have seen , benzyl alcohol and allyl alcohol react as rapidly as a tertiary alcohol with the Lucas Reagent; allyl chloride , however is soluable in the reagent. Ref. Morrison & Boyd 2ed. pg.545

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.

I 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.

Just hold on to the thread...that keeps us going
http://www.chiapaslink.ukgateway.net/
 
 
 
 
    WizardX
(Wizard Master)
07-31-04 04:04
No 522824
      I apologize for this error.     

The Lucas reagent is used as a test for alcohol groups. ie. primary alcohol, secondary alcohol, tertiary alcohol.

primary alcohol < secondary alcohol < tertiary alcohol

Primary alcohols are the least reactive towards the Lucas reagent. Secondary alcohols are more reactive towards chlorination (slow at room temperature), and tertiary alcohols react at room temperature immediately.



.......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




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?

 
 
 
 
    ahgreich
(Hive Bee)
07-31-04 20:46
No 522951
      benzyl chloride     

for benzyl chloride, why not just mix benzyl alcohol and muriatic acid and heat gently? Works quickly.
 
 
 
 
    dwarfer
(esoteric)
08-06-04 22:15
No 524034
      The following technique helps     


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



----------------------------------------


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





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.
crazyfrown

<<on 3rd microwavelaugh

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....


dwarfer
 
 
 
 
    UncleFester
(Popular Author)
08-23-04 00:06
No 526810
      some quick questions...     

Has anyone tried NiCl2, versus ZnCl2 and compared the yields? Secondly, wouldn't there be a problem with aziridine formation by basing the cloroephedrine with NaOH for extraction? Finally, to get back to the guy's original question, if NiCl2 works well for making chloroephedrine, then wouldn't tossing in some zinc dust make for a one pot quick and maybe dirty hydrogenation to meth? Just wondering because those materials are very easy to get in quantity.
 
 
 
 
    WizardX
(Wizard Master)
08-23-04 04:15
No 526892
      ZnCl2     

ZnCl2 as the Lucas Reagent. Other ZnCl2 and NiCl2 chlorination methods can be found in Vogel. n-BUTYL CHLORIDE http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0142
 
 
 
 
    java
(Hive Addict)
10-15-04 18:45
No 535978
      Ref; Chlorination Methods for Alcohols     

WizardX....I have folowed and read the thread and still have a question. Although I asked about chlorination of primary alcohols I wasn't clear that the primary alcohol wasn't a benzylic alcohol, but an aliphatic arene alcohol , namely Phenylalaninol.  Now  this Luca's test which chlorinates the alcohols, doesn't seem like it would work on this case, can you suggest a method not including thionyl chloride nor any of the Phosphorous halided , since they are not available  to me. I read the N-butyl chloride reference you provided , while its a primary alcohol , it's not an aromatic. .........or are you suggesting there is a chance that it may work........java


Note edited by java
 
This reference was found in the butyl chloride reference given by wizard x and was retrieved by Lugh.....

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




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


It is better to die on your feet than to live on your knees...Emiliano Zapata
 
 
 
 
    WizardX
(Wizard Master)
10-16-04 06:51
No 536042
      halogenation     

Java: Although the Lucas reagent is not the best halogenating reagent, compared to thionyl chloride or the PX3 & PX5 (X  = Cl, Br, I); it will certainly chlorinate. I suggest experiment on a very small scale with some Phenylalaninol. As a control, get or make some C6H5CH2CH2CH2OH and run this simultaneously in another flask.

C6H5CH2CH2CH2OH + ZnCl2/HCl ==> C6H5CH2CH2CH2Cl  oily liquid on the bottom of the lucas reagent.

The control will give you a good indication on the reaction time at room temperature or heating.

The amine on the phenylalaninol will make it soluble in the lucas reagent.

Another method is phenylalaninol + HI/RP, gently heat for 1-2 hours.