Author Topic: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation (Read 308 times)

atara · « **on:** October 24, 2011, 03:42:36 PM »

Starting point: sesamol.

http://en.wikipedia.org/wiki/Sesamol

Reducing a phenol is hard, which is why this hasn't usually taken us anywhere...

http://onlinelibrary.wiley.com/doi/10.1002/0471264180.or001.05/full

The Bucherer rearrangement converts a highly activated phenol or usually a naphthol to an aniline. It is usually done with naphthols though it does proceed with resorcinol, which looks rather similar to sesamol (logic!). Reagents are just ammonia and ammonium bisulfite.

Step 2: diazotization

http://en.wikipedia.org/wiki/Meerwein_arylation

http://en.wikipedia.org/wiki/Methyl_methacrylate

http://www.orgsyn.org/orgsyn/orgsyn/prepcontent.asp?print=1&showprint=1&rxntypeid=2&prep=CV6P0021

Sesamol-diazonium adds to methyl methacrylate so that the phenyl is on the 1- carbon and the chloro- is on the 2-carbon. It is better at this point not to eliminate the halide.

The resulting compound undergoes nucleophilic substitution on methylamine giving MDMA with a carboxylic acid methyl ester on the alpha carbon.

Hydrolysis/decarboxylation gives MDMA.

java · « **Reply #1 on:** October 24, 2011, 05:29:29 PM »

.....it looks interesting, have you considered making the OH into a I or Br then attaching that to an enolated acetone to get it alkylated with a carbonyl group, where it can be reductive-amination with ammonia for MDA or methylamine for MDMA......just a thought.....java

Reference Information

http://www.erowid.org/archive/rhodium/chemistry/mda.dalcason.html

akcom · « **Reply #2 on:** October 24, 2011, 09:19:16 PM »

I bet you could just couple the aryl halide to a tosylate or boronate with palladium. It's usually tolerant of amine functional groups

akcom · « **Reply #3 on:** October 25, 2011, 08:51:27 PM »

Convert to the bromide. Couple to acetone. Buchwald is the man, as always. Ligand free, OTC, thats the best part.

Tungsten. · « **Reply #4 on:** October 25, 2011, 08:56:10 PM »

Quote from: akcom on October 25, 2011, 08:51:27 PM

Convert to the bromide. Couple to acetone. Buchwald is the man, as always. Ligand free, OTC, thats the best part.

How is a Buchwald-Hartwig reaction of any use at all (assuming that is the reaction that you are talking about)?

atara · « **Reply #5 on:** October 25, 2011, 10:21:20 PM »

Phenols don't convert to aryl halides as easily as you guys seem to imagine; you can't convert a phenol to a bromide the way you convert an alcohol. As a result, you cannot perform a Buchwald starting with sesamol.

The Bucherer is a complex reaction that depends on the tautomerism of a phenol to a ketone and the formation of a bisulfite adduct. I'm not even perfectly sure it will proceed on sesamol -- as I said, it works on resorcinol -- though I suspect it will, hence the thread.

POSEIDON · « **Reply #6 on:** October 25, 2011, 11:48:53 PM »

look this and try:

http://en.wikipedia.org/wiki/Lucas'_reagent

lugh · « **Reply #7 on:** October 26, 2011, 12:23:29 AM »

Resonance stabilization causes the halogenation of phenols to be electrophilic

The hydroxyl group is a ortho-para director

Please study the principles of organic chemistry more thoroughly, the end results from the effort applied

java · « **Reply #8 on:** October 26, 2011, 01:16:52 AM »

....another thought occurred to me....how about methylation of phenols hence benzyl type alcohols are easier to convert to aldehydes hence treatment with nitroethane and an amine to make the nitroalkene ...then reduced via Al amalgamation to the amine.....java

Note......"Most commonly, Me2SO4 is employed to methylate phenols."

http://www.cnn.com/2011/10/25/world/americas/tropical-weather/index.html

lugh · « **Reply #9 on:** October 26, 2011, 01:29:15 AM »

The applicable section from the chapter on electrophilic substitution reactions from The Chemistry of Phenols

akcom · « **Reply #10 on:** October 26, 2011, 01:31:47 AM »

@java
methylation of phenol is going to give you an aryl ether, not a benzyl alcohol?

Quote from: Tungsten. on October 25, 2011, 08:56:10 PM

Quote from: akcom on October 25, 2011, 08:51:27 PM
Convert to the bromide. Couple to acetone. Buchwald is the man, as always. Ligand free, OTC, thats the best part.
How is a Buchwald-Hartwig reaction of any use at all (assuming that is the reaction that you are talking about)?

I'm referring to work performed by Buchwald's group. He only explored aryl bromides in the paper, but I'm sure with a bit of tweaking aryl triflates would work just was well. With a bit of work, you'll find the reference.

But fuck it, why not just start with catechol and do it by the book?

java · « **Reply #11 on:** October 26, 2011, 03:44:07 AM »

Quote from: akcom on October 26, 2011, 01:31:47 AM

@java
methylation of phenol is going to give you an aryl ether, not a benzyl alcohol?

Quote from: Tungsten. on October 25, 2011, 08:56:10 PM
Quote from: akcom on October 25, 2011, 08:51:27 PM
Convert to the bromide. Couple to acetone. Buchwald is the man, as always. Ligand free, OTC, thats the best part.
How is a Buchwald-Hartwig reaction of any use at all (assuming that is the reaction that you are talking about)?
I'm referring to work performed by Buchwald's group. He only explored aryl bromides in the paper, but I'm sure with a bit of tweaking aryl triflates would work just was well. With a bit of work, you'll find the reference.

But fuck it, why not just start with catechol and do it by the book?

......correct on that, i guess i was wishful thinking but not very clear....thanks....

POSEIDON · « **Reply #12 on:** October 27, 2011, 03:55:33 AM »

Quote from: lugh on October 26, 2011, 12:23:29 AM

Resonance stabilization causes the halogenation of phenols to be electrophilic The hydroxyl group is a ortho-para director Please study the principles of organic chemistry more thoroughly, the end results from the effort applied

Look this article
Studies in Organophosphorus Chemistry. I. Conversion of Alcohols and Phenols to Halides by Tertiary Phosphine Dihalides
G. A. Wiley, R. L. Hershkowitz, B. M. Rein, B. C. Chung
J. Am. Chem. Soc., 1964, 86 (5), pp 964–965
DOI: 10.1021/ja01059a073
Publication Date: March 1964
http://pubs.acs.org/doi/abs/10.1021/ja01059a073

java · « **Reply #13 on:** October 27, 2011, 10:53:35 AM »

Reference Information

Studies in Organophosphorus Chemistry. I. Conversion of Alcohols and Phenols to Halides by Tertiary Phosphine Dihalides
G. A. Wiley, R. L. Hershkowitz, B. M. Rein, B. C. Chung
J. Am. Chem. Soc.,
1964, 86 (5), pp 964–965
DOI: 10.1021/ja01059a073

lugh · « **Reply #14 on:** October 27, 2011, 11:06:27 AM »

Despite the title of the article, no phenols are listed in the table

akcom · « **Reply #15 on:** October 27, 2011, 04:03:40 PM »

"Table I and eq. 2 give some indication of the scope of the reaction."
Equation 2 gives the aromatic halides that are compatible with this reaction. Looks like yields with sesamol will be lower. The only example of a p-electron donating group is in 60% yield.

Sedit · « **Reply #16 on:** October 27, 2011, 04:31:45 PM »

Quote from: lugh on October 27, 2011, 11:06:27 AM

Despite the title of the article, no phenols are listed in the table

Right away I have spotted two, Cyclohexyl and cyclopentyl in table one.

lugh · « **Reply #17 on:** October 27, 2011, 05:56:32 PM »

Quote

Right away I have spotted two, Cyclohexyl and cyclopentyl in table one.

By definition, a phenol is a hydroxyl group bonded to a benzene ring:

h**p://en.wikipedia.org/wiki/Phenol

The alcohols mentioned above aren't aromatic

Please study organic chemistry more thoroughly when there's spare time

It's possible that sesamol can be halogenated in this manner since there are citations mentioned in the article that might say how to do it

The end results from the effort applied

akcom · « **Reply #18 on:** October 27, 2011, 10:11:52 PM »

I still think you'd be much better off just starting from catechol, ring closing, then brominating with NBS or H2O2 and Br2.

java · « **Reply #19 on:** October 28, 2011, 04:17:12 AM »

Quote from: java on October 26, 2011, 01:16:52 AM

....another thought occurred to me....how about methylation of phenols hence benzyl type alcohols are easier to convert to aldehydes hence treatment with nitroethane and an amine to make the nitroalkene ...then reduced via Al amalgamation to the amine.....java

Note......"Most commonly, Me2SO4 is employed to methylate phenols."

http://www.cnn.com/2011/10/25/world/americas/tropical-weather/index.html

......well then use .....maybe it can be done with heliotropin, to make the nitroalkene, and reduce it to the amine (MDA), with amalgamated aluminum.......then methylate to MDMA

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Author Topic: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation (Read 308 times)

atara

Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

java

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

akcom

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

akcom

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

Tungsten.

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

atara

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

POSEIDON

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

lugh

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

java

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

lugh

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

akcom

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

java

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

POSEIDON

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

java

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

lugh

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

akcom

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

Sedit

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

lugh

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

akcom

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation

java

Re: Sesamol part 2 ver. Bucherer rearrangement, Meerwein arylation