Sciencemadness Discussion Board

Phenylpropanones (P2P) from anilines

Lego - 22-2-2008 at 08:25

A chinese group continued the work which was started in the Hive (without giving the proper credits).

Facile Synthesis of 1-Aryl-2-propanones from Aromatic Amine
Li Li, Hongbiao Chen and Yuanbin Lin
Synthetic Communications 2007, 37(6), 985-991

Abstract: A facile synthesis of aryl propanones using aromatic amines as precursors, via an improved Meerwein arylation reaction under mild conditions, is reported.

Thanks to Solo for the full article:
https://sciencemadness.org/talk/viewthread.php?action=attach...


Experimental:
A procedure for the synthesis of product 2 [3-trifluoromethyl phenyl propanone] is as follows: m-trifluoromethylaniline hydrochloride, prepared by heating a mixture of 24.26 g (0.15 mol) of m-trifluoromethylaniline, 38 mL of concentrated hydrochloric acid, and 55 mL of water for several minutes, was cooled to -5°C in an ice-salt bath, and a cold solution of 10.6 g (0.15 mol) sodium nitrite in 15 mL of water was added over 45 min with stirring. The temperature of the reaction mixture was held between -5 and 2°C. The mixture was stirred for an additional 15 min, and a cold solution of 12.04 g (0.19 mol) of boric acid in 39 mL 40% of hydrofluoric acid was slowly added with stirring. The mixture was stirred for an additional 30 min and then stored at about 0°C for 2 h. The mixture was filtered, and the solid was washed with the dilute solution of fluoroboric acid (30 mL), 50% ethanol (30 mL), 95% ethanol (30 mL), and anhydrous ether (2 x 30 mL) to yield 36.7 g (95%) of the colorless salt 1 [3-trifluoromethylphenyl diazonium tetrafluoroborate].
To a stirred mixture of 20.5 g (0.25 mol) of anhydrous sodium acetate, 1.89 g (0.013 mol) of cuprous oxide, and 52.6 mL (0.468 mol) of isopropenyl acetate, 26.3 g (0.1 mol) of solid m-trifluoromethylphenyl diazonium tetrafluoroborate 1 were added over 30 min, while the temperature of the reaction mixture was held between 20 and 25°C. The reaction mixture was stirred an additional 6 h at 20–25°C. The mixture was filtered and washed with ether. The solution was collected and distilled under vacuum to give 19.4 g (95%) of the product 2 [3-trifluoromethyl-P2P] as a clear yellow liquid.

----

The yield is for sure exaggerated but anyway it proves that the method is useful for the synthesis of ring substituted P2P derivatives.

The old thread in the Hive is archived here (unfortunately without the great pictures):
http://www.erowid.org/archive/rhodium/chemistry/p2p.meerwein...

bio2 - 22-2-2008 at 18:10

Well if the yield is anywhere close then it certainly is a great improvement over the previously reported 35-50% yield of the unsubstituted propanone.

I'm wondering how much the difference is due to the trifluoromethyl ring substitution and is the formed fluoborate
more labile to the rearrangement than the hydrochloride?

Nicodem - 23-2-2008 at 04:45

Note that they actually isolate the diazonium salt as its tetrafluoroborate salt. The improved yields are certainly the consequence of this step.

Sauron - 23-2-2008 at 09:22

That highly electronegative trifluoromethyl group in the 3-position...what are the implications for the reaction of aniline itself, or of electropositively substituted anilines?

WizardX - 23-2-2008 at 11:59

Quote:
Originally posted by Nicodem
Note that they actually isolate the diazonium salt as its tetrafluoroborate salt. The improved yields are certainly the consequence of this step.


Indeed! And also because the diazonium was synthesized at lower temperatures -5 and 2°C to improved yields.

zed - 20-8-2010 at 23:12

I thought the procedure was bizarre when I first read it.

Isolating solid Diazonium Salts is generally considered a big no-no. Tee, hee; in Vogel's 3rd edition of Practical Organic Chemistry, they filter away the solvents from a diazonium chloride, apparently, just for the heck of it. They then provide, this type of admonishment "For the love of God, whatever you do, don't let it completely dry out AND don't touch it with a hard object. It could explode."

Apparently, the Fluoro-Borate salts are unusually stable. In Vogel's 5th Ed., they form such a salt, dry it, and then crank up the heat. Thereby, decomposing it to a Fluorobenzene.

chemrox - 22-8-2010 at 00:06

Quote: Originally posted by Sauron  
That highly electronegative trifluoromethyl group in the 3-position...what are the implications for the reaction of aniline itself, or of electropositively substituted anilines?


I suppose that was a a factor in the rather stunning yield. Probably what led to a complete conversion to the diazonium.

Filemon - 26-8-2010 at 01:50

Does it also work with isopropenyl formate?

zed - 26-8-2010 at 19:14

You are burdened with an abundance of isopropenyl formate?

497 - 2-9-2011 at 00:16

Has anyone ever seen mention of haloarylating propylene with diazoniums? It seems like it would be pretty convenient, particularly if you had an easy source of an aniline. Propylene is easy to make, and available for purchase to some.

You might also be able to haloarylate methyl methacrylate and then decarboxylate to the same 1-aryl-2-halopropane.
I searched for a little bit and came up with nothing other than peer reviewed stuff.

http://books.google.com/books?id=leSpJbC1BqEC&pg=PA252&a...

http://www.sciencedirect.com/science/article/pii/S0040403998...

http://www.springerlink.com/content/d82161r378382166/

Edit
I don't know here would be a more appropriate place to put this:
http://www.google.com/url?sa=t&source=web&cd=5&v...
It talks about getting pretty high yields of propylene by pyrolysis of polyethylene. I'd always heard such a pyrolysis yielded a "useless mix of crap" and so nobody did it. Looks like that is not necessarily so.

[Edited on 3-9-2011 by 497]

497 - 11-4-2012 at 03:55

Hate to double post, but this looks very cool.
http://pubs.acs.org/doi/abs/10.1021/jo00203a003

Arylation of olefins by N-nitroso-N-arylacetamides under palladium(0) catalysis: a new precursor of arylpalladium species

Looks like you don't need the tetrafluoroborate after all :D

There's even an easily accessible N-arylacetamide to test it on! What could be easier?

Is there an alternative for isopropenyl acetate in Meerwein reaction?

ewel - 20-11-2014 at 02:27

The diazonium salts tend to react with acetone, which is the reason why it is not the best solvent for a Meerwein reaction. Instead of the wanted product it can form alpha-carbonyl-arylhidrazone compounds. Unfortunately acetone is formed from the isopropenyl acetate and is present during the reaction.

Is there an alternative acylating agent for isopropenyl actetate?

zed - 24-11-2014 at 19:42

Hunh? What procedure are you referring to?

davic - 3-6-2018 at 06:27

Has anyone actually tries the procedure reported in Synthetic Communications, 2007, 37(6) ?

Boffis - 3-6-2018 at 11:14

@Davic; which procedure? there are about 22 papers in issue 6. Can you give us a clue, like maybe a page number?

Chemi Pharma - 3-6-2018 at 11:47

The procedure is labeled: "Facile Synthesis of 1-Aryl-2-propanones
from Aromatic Amine" and I'm attaching it bellow in .pdf.

After request the article at "SM reference section", I saw that the link to the same paper have been posted by @solo, as @Lego have said at the first post of this thread.

Anyway, thanks @Mayko for the effort, who gently posted this paper at "SM reference section" replying my request.




Attachment: phenyl 2 propanone from aniline, NaNO2, fluoboric acid, isopropenyl acetate, NaOAc and CuCl.PDF (247kB)
This file has been downloaded 483 times

[Edited on 4-6-2018 by Chemi Pharma]

clearly_not_atara - 3-6-2018 at 12:36

Quote: Originally posted by 497  
Hate to double post, but this looks very cool.
http://pubs.acs.org/doi/abs/10.1021/jo00203a003

Arylation of olefins by N-nitroso-N-arylacetamides under palladium(0) catalysis: a new precursor of arylpalladium species
Actually, I am familiar with the nitrosoanilide method. I have investigated its use in the synthesis of arylacetones before.
The practical problem with this family of methods though is that there is no suitable alternative to isopropenyl acetate, and this latter compound is hard to make, requiring acetyl chloride or ketene. However, I also have an approach to fixing that.
By controlling the temperature of the Lucas rxn, it should be possible to selectively chlorinate the 2-hydroxy of propylene glycol. Reaction of 2-chloropropanol with sodium acetate then yields 2-acetoxypropanol. These two steps might even be done together if the acid in the Lucas reaction is neutralized by excess sodium acetate. Dehydration of this alcohol ought to be achievable.

If you can solve the question of dehydrating 2-acetoxy-1-propanol to isopropenyl acetate then you've got a chance of getting somewhere. The best method I can think of involves reaction with tosyl chloride and base-catalysed "dehydrohalogenation". But this transformation ought to be possible in one step, preferably at high temperature. Pyrosulfate (S2O72-) salts seem like an interesting approach because pyrolysing the sodium alkyl sulfate formed should selectively remove the hydroxy group. Hot pyrophosphoric acid might also work.

CuReUS - 4-6-2018 at 09:45

Quote: Originally posted by clearly_not_atara  
isopropenyl acetate is hard to make, requiring acetyl chloride or ketene.

Not necessarily ;)
1.From propene
https://link.springer.com/article/10.1023/B%3ARUCB.000004227...
https://www.sciencedirect.com/science/article/pii/S0022328X9...
https://link.springer.com/article/10.1007/BF02494811
https://pubs.acs.org/doi/10.1021/ja00298a024

2.From propyne (aka mapp gas)-https://pubs.acs.org/doi/10.1021/ja01323a047

3.From allyl acetate-https://pubs.acs.org/doi/abs/10.1021/jo301984p

davic - 13-6-2018 at 01:54

sorry, pgs.985-991

clearly_not_atara - 13-6-2018 at 11:45

CuReUS: None of these procedures seem remotely practical.



This was an annoying post to read and critique: none of the links have available descriptions, and all of them appear to either not synthesize the right compound or to depend on highly complex and impractical catalysts or precursors.
Furthermore it appears that you put much less effort into making your post than was required of me in order to determine if it was any value; you simply pasted the results of a SciFinder search without checking to see if the links were any good. The result was that any potential discussion of making isopropenyl acetate was hung up on the need to evaluate all of these links which ultimately turned out to be a waste of time. This is rather disappointing from someone who usually makes informative and useful posts.

Quote: Originally posted by davic  
sorry, pgs.985-991


From the paper:

"To a stirred mixture of 20.5 g (0.25 mol) of anhydrous sodium acetate, 1.89 g (0.013 mol) of cuprous oxide, and 52.6 mL (0.468 mol) of isopropenyl acetate, 26.3 g (0.1 mol) of solid m-trifluoromethylphenyl diazonium tetrafluoroborate 1 were added over 30 min, while the temperature of the reaction mixture was held between 20 and 25C. The reaction mixture wasstirred an additional 6 h at 20–25 C. The mixture was filtered and washed with ether. The solution was collected and distilled under vacuum to give 19.4 g (95%) of the product2 as a clear yellow liquid."

Isopropenyl acetate is used in a large excess. I doubt this procedure will be applied by anyone here.

Attachment: hering2012.pdf (517kB)
This file has been downloaded 504 times

CuReUS - 13-6-2018 at 21:18

first of all,I am sorry.I wouldn't intentionally waste anyone's time:(
Quote: Originally posted by clearly_not_atara  
CuReUS: None of these procedures seem remotely practical.

the refs were meant for you,not home chemists.I thought since you were a professional chemist you could get some of the catalysts mentioned in those papers.
Quote:
https://link.springer.com/article/10.1023/B%3ARUCB.000004227...
I'm not even sure this produces the right isomer, vs. allyl acetate

it produces both,the ratio depends on partial pressure of O2.More pressure favors formation of isopropenyl acetate.Anyways it wouldn't matter because you just convert the allyl acetate to isopropenyl via the last link.
Quote:
https://www.sciencedirect.com/science/article/pii/S0022328X9...
Abstract only mentions allylic esters and disproportionations, no vinylic esters of acyclic alkenes. Given that vinyl esters are a useful FG it would be strange not to mention a method that produces them.

pg 278,table 1 - 0.986 mol of isoproprenyl acetate/mol of Pd
Quote:
https://link.springer.com/article/10.1007/BF02494811
From the abstract: "the oxidative esterification at the vinylic position is absent"

the complete sentence is - " The oxidation of alkenes in aprotic media (CHCl3, CH2Cl2, CO2, THF) affords mainly allylic esters and the oxidative esterification at the vinylic position is absent.
In AcOH,you get same yield as the previous paper.
All the Pd papers are by the same authors,just arranged in chronological order.
Quote:
MAPP is no longer produced by anyone

I was unaware of this,Sorry
Quote:
https://pubs.acs.org/doi/abs/10.1021/jo301984p
Title is "Visible light-mediated alpha-arylation of enol acetates using aryl diazonium salts". Abstract gives no hint as to how isopropenyl acetate is made here. So I downloaded the paper and attached it. It contains no mention of synthesizing isopropenyl acetate or any vinyl acetate, and it does not mention allyl acetate at all. What the paper does contain (page 10349) is a description of how to make enol acetates from ketones using "2-propenyl acetate"

Exactly.So if you use acetone as the ketone here,wouldn't you get isopropenyl acetate ?
also,allyl acetate IS 2-propenyl acetate

[Edited on 14-6-2018 by CuReUS]

notoxicshit - 14-6-2018 at 13:43

I can buy mapp gas in germany easily. Who wants some?

Chemi Pharma - 15-6-2018 at 11:01

Quote: Originally posted by clearly_not_atara  


From the paper:

"To a stirred mixture of 20.5 g (0.25 mol) of anhydrous sodium acetate, 1.89 g (0.013 mol) of cuprous oxide, and 52.6 mL (0.468 mol) of isopropenyl acetate, 26.3 g (0.1 mol) of solid m-trifluoromethylphenyl diazonium tetrafluoroborate 1 were added over 30 min, while the temperature of the reaction mixture was held between 20 and 25C. The reaction mixture wasstirred an additional 6 h at 20–25 C. The mixture was filtered and washed with ether. The solution was collected and distilled under vacuum to give 19.4 g (95%) of the product2 as a clear yellow liquid."

Isopropenyl acetate is used in a large excess. I doubt this procedure will be applied by anyone here.


I don't think so @clearly. Making diazonium tetrafluoborate arenes is easy if you have 50% w/w solution fluoboric acid as I have. Sodium nitrite, HCl, Anhydrous sodium acetate and cuprous oxide (or cuprous chloride either, as wrote in the paper with high yield too) are easy to get reagents.

The only reagent that really sucks is isopropenyl acetate, but it's sold by Sigma Aldrich for U$130,00 a kilogram. Product nº 10914 and CAS nº 108-22-5. I'm thinking to buy some and experiment this procedure to see how it works.

Loptr - 15-6-2018 at 12:58

In the USA, isopropenyl acetate has recently become available to the general public.

Now is a prime time to be able to acquire it easily.

:)

S.C. Wack - 15-6-2018 at 15:20

Quote: Originally posted by ewel  
The diazonium salts tend to react with acetone, which is the reason why it is not the best solvent for a Meerwein reaction. Instead of the wanted product it can form alpha-carbonyl-arylhidrazone compounds. Unfortunately acetone is formed from the isopropenyl acetate and is present during the reaction.


Yet acetone is used as solvent elsewhere. For instance the patent from
https://the-hive.archive.erowid.org/forum/showflat.pl?Cat=&a...
(notice Nicodem saying the same, exactly as in copy/paste, and the absence of HBF4 in the process)
and, in this:

A Practical Synthesis of a-Aryl Methyl Ketones via a Transition-Metal-Free Meerwein Arylation
Carmela Molinaro, Jeffrey Mowat, Francis Gosselin, Paul D. O’Shea, Jean-Francüois Marcoux, Remy Angelaud, and Ian W. Davies
J. Org. Chem. 2007, 72, 1856-1858
http://dx.doi.org/10.1021/jo062483g

Attachment: joc_72_1856_2007.pdf (1.6MB)
This file has been downloaded 553 times

Acetone to P2P via ketene

Dorsoris - 16-6-2018 at 16:08

I'm working on a scheme involving an upgrading of acetone involving pyrolysis to form intermediate ketene which is further reacted with acetone to formisopropenyl acetate which is separated from the reaction as a liquid.

The isopropenyl acetate is reacted further with diazotized aniline to form phenyl-2-propanone(P2P). I can delete & repost this part if this is not the correct forum for P2P chemistry.

[file]68881[/file]

P2P from acetone via ketene.jpg - 25kB

Dorsoris - 16-6-2018 at 16:20

This chemistry was developed by a major chemical company around the m-trifluoromethyl derivative as a starting material for the now banned diet drug fenfluramine. It's still in a box of my file cabinet contents from a move.

Dorsoris - 16-6-2018 at 18:14

I envision 2 zones: first, the high temperature reaction zone to convert acetone feed into ketene in the vapor phase; second, a reaction zone where the ketene would be reacted with an excess of acetone followed by a condenser phase where the mixed acetone & isopropenyl acetate would be isolated as a mixture of 2 liquids. This mixture would be fractionally distilled to remove the more volatile acetone, which would be recycled.

zed - 25-6-2018 at 16:09

There is a YouTube video on the subject.

https://www.youtube.com/watch?v=g9sPlMkYEIw&t=188s

Excellent opportunities for death, while working with Ketene.

Likewise, Anilines and Benzene Diazonium Salts.

[Edited on 26-6-2018 by zed]

[Edited on 26-6-2018 by zed]

VSEPR_VOID - 26-6-2018 at 19:41

I am working on something a lot better, starting maybe from either aspirin, beznyl alcohol, or benzoic acid; not anilines.