Author Topic: The Meerwein Reaction  (Read 6326 times)

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PEYOTE

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The Meerwein Reaction
« on: October 10, 2001, 07:54:00 PM »
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

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Re: The Meerwein Reaction
« Reply #1 on: October 10, 2001, 08:43:00 PM »
So what? Is it of any relevance for phenylethylamine chemistry?

PolytheneSam

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Re: The Meerwein Reaction
« Reply #2 on: October 11, 2001, 01:15:00 AM »
If Z was CH3 then you would get propenylbenzene.

http://www.geocities.com/dritte123/PSPF.html

Rhodium

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Re: The Meerwein Reaction
« Reply #3 on: October 11, 2001, 02:46:00 AM »
CH3 is not an electron-withdrawing group.

PolytheneSam

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Re: The Meerwein Reaction
« Reply #4 on: October 11, 2001, 03:43:00 AM »
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



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jim

  • Guest
Re: The Meerwein Reaction
« Reply #5 on: October 11, 2001, 05:45:00 AM »
Isn't an amine an effective electron withdrawing substituant, just like C=O, or CN?

PEYOTE

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Re: The Meerwein Reaction
« Reply #6 on: October 11, 2001, 02:09:00 PM »
Mmmmhhh, I dont think so... And then you must use a tertiary amine because with a double bond the enamine makes an imine....

hypo

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Re: The Meerwein Reaction
« Reply #7 on: October 11, 2001, 04:29:00 PM »
would nitro-ethene or 2-nitro-propene work? and how would you get interesting diazonium-benzenes?

Rhodium

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Re: The Meerwein Reaction
« Reply #8 on: October 11, 2001, 04:43:00 PM »
Diazoniumbenzenes are made by treating anilines with HNO2 at 0-5°C.

Nitroethene doesn't sound too bad.

zed

  • Guest
Thank you Peyote!
« Reply #9 on: April 27, 2002, 07:18:00 AM »
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

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Stripping monomoers off polymers?
« Reply #10 on: April 28, 2002, 06:24:00 AM »

zed

  • Guest
No link!
« Reply #11 on: April 28, 2002, 09:56:00 AM »
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

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decarbox. m-dopa analogs?
« Reply #12 on: April 28, 2002, 07:05:00 PM »
zed: do you have any ref. on decarbox. of m-dopa analogs?
if so, then, please, post it.
;)

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zed

  • Guest
Nope!
« Reply #13 on: April 29, 2002, 05:20:00 AM »
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

  • Guest
found ref.!
« Reply #14 on: April 30, 2002, 01:35:00 PM »
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.

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Rhodium

  • Guest
strecker degradation
« Reply #15 on: April 30, 2002, 01:39:00 PM »
That article is good, I have read it. They use the strecker degradation (sodium hypochlorite) on the phenylalanine to get the phenylacetaldehyde.

Aurelius

  • Guest
Degradation
« Reply #16 on: April 30, 2002, 07:23:00 PM »
hey Rhodium,do you remember the details on how that was performed?

Rhodium

  • Guest
Sorry, don't remember.
« Reply #17 on: April 30, 2002, 07:38:00 PM »
Sorry, don't remember.

PEYOTE

  • Guest
Well...
« Reply #18 on: April 30, 2002, 07:49:00 PM »
Tomorrow I'll search it for you guyz, okay?

Let me scan and OCR it, a couple of dayz....

zed

  • Guest
alpha-methyl- phenylalanines.
« Reply #19 on: May 04, 2002, 08:34:00 AM »
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?