PEYOTE (Hive Bee)
10-10-01 19:54
No 222804
      The Meerwein Reaction  Bookmark   

From J. March, Advanced Organic Chemistry, 4th edition, pp. 716-718, 4-19


Global reaction:
Z-C=C-H + Ar-N2+Cl- =(CuCl2)=> Z-C=C-Ar



Olefins activated by an electron-withdrawing group (Z may be C=C, halogen, C=O, Ar, CN, etc...) can be arylated by tretment with diazonium salt and a cupric chloride(1) catalyst. This is called Meerwein arylation reaction(2). Addition of ArCl to the double bond (to give Z-C(Cl)-C(H)-Ar) is a side reaction(3). In an improved procedure, an arylamine is treated with an alkyl nitrite (generating Ar-N2+ in situ) and a copper(II) halide in the presence of the olefin(4). The mechanism is probably of the free-radical type, with Ar. forming as in Sandmeyer reaction(5) and then(6):

Ar. + H-C=C => Ar-CH-C. =(CuCl2)=> Ar-C=C + CuCl   (Principal)
Ar. + H-C=C => Ar-CH-C. =(CuCl2)=> Ar-CH-CCl =(-HCl)=> Ar-C=C   (side rxn)

The radical Ar-CH-C. can react with cupric chloride by two pathways, one of which leads to addition and other to substitution. Even when the addition pathway is taken, however, the substitutionn product may still be formed by subsequent elimination of HCl.




(1) FeCl2 is also effective: JOC USSR, 17:765(1981)
(2) for reviews see: Russ. Chem. Rev., 53:943-55(1984); Org. React, 24:225-59(1976)
(3) J. March, pp. 820-1: ArX can be added across double bonds, in a free-radical process, by treatment of olefins with diazonium salts, although Meerwein arylation (substitution) competes.
(4) JOC, 42:2431(1977)
(5) J. March, p. 723:
    Ar-N2+X- + CuX => Ar. + N2 + CuX2
    Ar. + CuX2 => ArX + CuX
(6) JACS, 84:4150(1962) and 84:4152(1962)
 
 
 
 
    Lilienthal
(Moderator)
10-10-01 20:43
No 222821
      Re: The Meerwein Reaction  Bookmark   

So what? Is it of any relevance for phenylethylamine chemistry?
 
 
 
 
    PolytheneSam
(Master Searcher)
10-11-01 01:15
No 222912
      Re: The Meerwein Reaction  Bookmark   

If Z was CH3 then you would get propenylbenzene.

http://www.geocities.com/dritte123/PSPF.html
 
 
 
 
    Rhodium
(Chief Bee)
10-11-01 02:46
No 222936
      Re: The Meerwein Reaction  Bookmark   

CH3 is not an electron-withdrawing group.
 
 
 
 
    PolytheneSam
(Master Searcher)
10-11-01 03:43
No 222968
      Re: The Meerwein Reaction  Bookmark   

I should have read the whole thing first.  How about using methyl methacrylate monomer?  I have an old chemical experiments book with an experiment in it where they slowly heat the polymer which depolymerizes and the monomer is distilled off.  The polymer is also known as acrylic, plexiglass or lucite.
Once you have the phenyl group on the methyl methacrylate, then hydrogenate the double bond on the side chain, make the amide and use the Hoffmann degradation to make amphetamine (if C6H5N2+ was used)

Reduction of cinnamic acid to hydrocinnamic acid:  http://www.orgsyn.org/prep.asp?prep=cv1p0311
Note Hofmann degradation of hydrocinnamide here (reference 11):  http://www.orgsyn.org/prep.asp?prep=cv3p0720

http://www.geocities.com/dritte123/PSPF.html
 
 
 
 
    jim
(Hive Bee)
10-11-01 05:45
No 223026
      Re: The Meerwein Reaction  Bookmark   

Isn't an amine an effective electron withdrawing substituant, just like C=O, or CN?
 
 
 
 
    PEYOTE
(Hive Bee)
10-11-01 14:09
No 223134
      Re: The Meerwein Reaction  Bookmark   

Mmmmhhh, I dont think so... And then you must use a tertiary amine because with a double bond the enamine makes an imine....
 
 
 
 
    hypo
(Hive Bee)
10-11-01 16:29
No 223170
      Re: The Meerwein Reaction  Bookmark   

would nitro-ethene or 2-nitro-propene work? and how would you get interesting diazonium-benzenes?
 
 
 
 
    Rhodium
(Chief Bee)
10-11-01 16:43
No 223176
      Re: The Meerwein Reaction  Bookmark   

Diazoniumbenzenes are made by treating anilines with HNO2 at 0-5C.

Nitroethene doesn't sound too bad.
 
 
 
 
    zed
(Newbee)
04-27-02 07:18
No 301977
      Thank you Peyote!  Bookmark   

The post on the Meerwein reaction was interesting. I studied this reaction a bit at one time. Herein was my goal.

To find under what conditions the "So called" side reaction was favored. Where ArN2+Cl- adds to Methyl Methacrylate to produce ArCH2-CCl(COOR)CH3.

This Halogenated Carboxylic acid should react quite readily with ammonia or amines, to produce analogs of MethylDopa.

These analogs might then be decarboxylated/decomposed to produce phenyl-isopropylamines, or phenyl2propanones.

Granted, the overall yield might not be great, but as I recall, the reaction might be carried out in water. At the time Methyl Methacrylate was easy to come by, as was Aniline.

Have you explored this reaction sequence?

This might also answer some of the earlier posted questions.

Thank you for your post.............zed
 
 
 
 
    Flinger
04-28-02 06:24
      Stripping monomoers off polymers?
(Rated as: UTFSE!)
 Bookmark   
 
 
 
    zed
(Hive Bee)
04-28-02 09:56
No 302451
      No link!  Bookmark   

No link, but I think I recall, Methyl Methacrylate being recovered by destructive distillation of Lucite. This will reek bigtime. Seems to me Methyl Methacrylate is a very irritating lacrimator. It used to be about as expensive as retail beer, probably still very cheap in bulk.

Foxy2, refers to The desructive distillation of polystyrene to produce styrene, in the Phenylacetic Acid post of last week. Once again, you should expect this distillation to reek. Once again, styrene monomer casting resin or reagent is fantastically cheap.

Sorry, I couldn't be of more help...............zed
 
 
 
 
    kurupira
(Stranger)
04-28-02 19:05
No 302589
      decarbox. m-dopa analogs?  Bookmark   

zed: do you have any ref. on decarbox. of m-dopa analogs?
if so, then, please, post it.
wink

????????????????????????????????????????????????????????????
 
 
 
 
    zed
(Hive Bee)
04-29-02 05:20
No 302827
      Nope!  Bookmark   

K, this I do not have. The idea of decarboxylating amino acids to produce amines has been around awhile. But, the first good lab proceedures started showing up in chem. lit. about 30 years ago. This is quite recent, and people are still playing with proceedures. As such, I don't know what work has been done on compounds with such an unusual structure.

We are employing some reverse engineering here. The usual proceedure, is to produce this amino acid by an addition to a phenyl-2-propanone. Most people haven't been trying to run the reaction in the opposite direction.

Before, I expended a lot of energy on running the Meerwein, I would obtain a little Methyl-dopa and see how it reacts. It is a somewhat common medication for Hypertension.

If I recall correctly, it isn't very stable. Under some conditions, it may like to both transaminate, and decarboxylate, to produce a phenyl-2-propanone.

This material decomposes at 300.

I will refer to the original patent information to refresh my memory.
 
 
 
 
    kurupira
(Stranger)
04-30-02 13:35
No 303321
      found ref.!  Bookmark   

i just found one ref. at TFR (the fucking results)look at this:
JOC vol.29, pp.1424-1428 (1964) titled "Degradation of a-Methyl-3,4-dihydroxyphenylalanine (a-MethylDOPA)".
but libraries here doesn't have old JOC volumes.

????????????????????????????????????????????????????????????
 
 
 
 
    Rhodium
(Chief Bee)
04-30-02 13:39
No 303322
      strecker degradation  Bookmark   

That article is good, I have read it. They use the strecker degradation (sodium hypochlorite) on the phenylalanine to get the phenylacetaldehyde.
 
 
 
 
    Aurelius
(Hive Bee)
04-30-02 19:23
No 303391
      Degradation  Bookmark   

hey Rhodium,do you remember the details on how that was performed?
 
 
 
 
    Rhodium
(Chief Bee)
04-30-02 19:38
No 303397
      Sorry, don't remember.  Bookmark   

Sorry, don't remember.
 
 
 
 
    PEYOTE
(Hive Bee)
04-30-02 19:49
No 303404
      Well...  Bookmark   

Tomorrow I'll search it for you guyz, okay?

Let me scan and OCR it, a couple of dayz....
 
 
 
 
    zed
(Hive Bee)
05-04-02 08:34
No 304810
      alpha-methyl- phenylalanines.  Bookmark   

U.S. Patent 2,868,818 Contains several good proceedures, for producing Alpha-methylphenylalanines from Phenyl-2-propanones. They utilize KCN and Ammonium Carbonate to form a hydantoin, which is then hydrolysed to form the Alpha-Methyl- phenylalanine.

If these amino acids decarboxylate to amines, as most amino-acids do when heated. It is a very interesting reaction sequence. It would produce a phenyl-isopropyl-amine, from a phenyl-2-propanone, without using a reduction as we normally think it. No hydrogen, No disolving metals, no formamide, no metal hydrides. Might not prove practical, but it is interesting.

Which takes us back to the Meerwein Reaction. I'll work on references.

And, of course, the big question, do those Alpha-Methyl-Phenylalanines, decarboxylate to form Phenylisopropylamines? These Phenyalanines do decompose at their M.P.... But, to what?