Sciencemadness Discussion Board

Diphenyl Ether From Phenol?

The Chemistry Shack - 4-8-2015 at 16:02

I was wondering if it is possible to make diphenyl ether from phenol via an acid-ether synthesis (using H2SO4 catalyst) instead of using a Williamson ether synthesis. The Williamson ether synthesis would not be an issue, I would just prefer to do the first method as I wouldn't need to make bromobenzene (I'm pretty lazy, so the less work, the better :P)

Nicodem - 4-8-2015 at 16:35

No, it is not possible to condense phenol to diphenyl ether with sulfuric acid. See the mechanism of acid catalyzed ether formation and you will see why it does not apply to phenol.

Williamson ether synthesis with phenol and bromobenzene is impossible, as bromobenzene does not undergo SN2 substitutions for obvious reasons. However, these two reactants give diphenyl ether in the Ullmann condensation reaction. Arylations of phenols work well also with palladium based catalysts (via oxidative addition of iodo- or bromobenzenes followed by halide/phenolate ligand exchange and finally reductive elimination). With electron poor halobenzenes (for example with 4-fluoronitrobenzene, etc.) direct arylation or phenols is possible via aromatic nucleophilic substitution (but this does not work with PhBr).

The Chemistry Shack - 4-8-2015 at 17:06

Quote: Originally posted by Nicodem  
No, it is not possible to condense phenol to diphenyl ether with sulfuric acid. See the mechanism of acid catalyzed ether formation and you will see why it does not apply to phenol.

Williamson ether synthesis with phenol and bromobenzene is impossible, as bromobenzene does not undergo SN2 substitutions for obvious reasons. However, these two reactants give diphenyl ether in the Ullmann condensation reaction. Arylations of phenols work well also with palladium based catalysts (via oxidative addition of iodo- or bromobenzenes followed by halide/phenolate ligand exchange and finally reductive elimination). With electron poor halobenzenes (for example with 4-fluoronitrobenzene, etc.) direct arylation or phenols is possible via aromatic nucleophilic substitution (but this does not work with PhBr).


Forgive my confusion, I am relatively new to O-chem and haven't studied any more than basic mechanisms like Nucleophilic substitution, condensation, addition, elimination, esterification, etc..

Does the acid-catalyzed synthesis not work with the phenol because the phenol is acidic, making it harder to protonate? Or is it something to do with the alkene groups?

Also, I misspoke about the Williamson synthesis. It is actually a modification of that mechansim using bromobenzene and Sodium phenoxide, according to the wiki article: https://en.wikipedia.org/wiki/Diphenyl_ether

"It is synthesized by a modification of the Williamson ether synthesis, here the reaction of phenol and bromobenzene in the presence of base and a catalytic amount of copper:

PhONa + PhBr → PhOPh + NaBr"

[Edited on 5-8-2015 by The Chemistry Shack]

Nicodem - 5-8-2015 at 01:06

Quote: Originally posted by The Chemistry Shack  
Does the acid-catalyzed synthesis not work with the phenol because the phenol is acidic, making it harder to protonate? Or is it something to do with the alkene groups?

The mechanism of the acid catalysed ether formation involves an SN2 in the ether bond formation step (in the case of tert-alcohols and certain others, it involves a SN1). Phenols obviously cannot undergo SN2 substitutions at the ipso position as that carbon is sp2 hybridized. SN1 is also impossible for phenols as phenyl carbocations are among the most instable carbocations of them all.

For the mechanism of this and the Willliamson reactions, see: http://www.mhhe.com/physsci/chemistry/carey/student/olc/ch15... (note the step 2 of the acid catalyzed reaction)
http://www.masterorganicchemistry.com/2014/11/14/ether-synth...
(and many other educational sites that you can find yourself)
Try applying that mechanism to phenol and you will see it simply cannot go.
Quote:
Also, I misspoke about the Williamson synthesis. It is actually a modification of that mechansim using bromobenzene and Sodium phenoxide, according to the wiki article: https://en.wikipedia.org/wiki/Diphenyl_ether

Don't take what Wikipedia authors write for granted. Either check the references or read further. That reference that Wikipedia cites uses the Ullmann condensation reaction, which is obviously something quite different from the Williamson reaction. Wikipedia acknowledges this by mentioning that copper catalysis is used, but oversimplifies by calling it a "modified Williamson ether synthesis". Whenever you see the word "modified" applied in organic synthesis, you need to be skeptical whether it is truly still the same reaction with the change in technique, conditions or reagents standing for the "modified", or is it actually mechanistically different. Such confusion sometimes appears even in the scientific articles. It is a fuzzy area, especially for reactions that can proceed through various pathways under overlapping conditions to give the same product (and there are many such).

The Chemistry Shack - 5-8-2015 at 05:02

Quote: Originally posted by Nicodem  

The mechanism of the acid catalysed ether formation involves an SN2 in the ether bond formation step (in the case of tert-alcohols and certain others, it involves a SN1). Phenols obviously cannot undergo SN2 substitutions at the ipso position as that carbon is sp2 hybridized. SN1 is also impossible for phenols as phenyl carbocations are among the most instable carbocations of them all.


Ok, thank you for the help. After looking at the mechanisms, it does make sense that SN2 won't work (it appears that the pi electrons get in the way of the oxygen's lone electron pair, making substitution impossible, although I might be misunderstanding this).

Quote: Originally posted by Nicodem  

For the mechanism of this and the Willliamson reactions, see: http://www.mhhe.com/physsci/chemistry/carey/student/olc/ch15... (note the step 2 of the acid catalyzed reaction)
http://www.masterorganicchemistry.com/2014/11/14/ether-synth...
(and many other educational sites that you can find yourself)
Try applying that mechanism to phenol and you will see it simply cannot go.


I have tried to apply the second step of the mechanism to phenol, and as I said before, from drawing everything out it seems as if the pi electrons on the phenol get in the way and prevent the nucleophilic oxygen from attaching to the ring, although I couldn't find any justification for this online, other than it seems to make sense to me.

And I will definitely note what you said about using wikipedia as a source for organic reactions!