Sciencemadness Discussion Board

De-Tert-Butylation of 4-t-butylacetophenone

johnames - 12-3-2011 at 19:05

Hello,

I am having trouble understanding the mechanism of de-tert-butylation specifically the de-tert-butylation of 4-t-butylacetophenone to acetophenone. Does this follow the same mechanism as Boc deprotection? I haven't found anything on the mechanism de-tert-butylation but have found various papers suggesting strong Lewis acids are a sufficient catalyst. I have also seen reports of aluminum chloride and various acid activated clays.

Can anyone help me understand the mechanism of de-tert-butylation or provide references for the de-tert-butylation of an aromatic aldehyde?

Thanks

UnintentionalChaos - 12-3-2011 at 21:17

It's a retro friedel-crafts alkylation. Same mechanism, but backward. IIRC, you usually add an activated aromatic ring to the reaction mix to behave as a t-butyl cation trap.

johnames - 12-3-2011 at 22:41

So a common Boc deprotection would work fine with added anisole?

UnintentionalChaos - 12-3-2011 at 22:58

Quote: Originally posted by johnames  
So a common Boc deprotection would work fine with added anisole?


Not even close. t-BOC looks nothing like a tert-butylbenzene and the mechanisms are wildly different. I found a mechanism for a friedel crafts alkylation and reaction conditions for a friedel-crafts dealkylation using simple google searches. I'm sure you can manage to do the same now that you know what to look for.

johnames - 12-3-2011 at 23:58

Thanks. Looks like FeCl3 in toluene should do the trick. Toluene should accept t-butyl so no need for the anisole.

Nicodem - 13-3-2011 at 10:49

You can check a review paper on the use of the t-butyl protecting group for positions on the aromatic rings: M. Tashiro, Synthesis, 1979, 921-936. I'm sure you will find plenty of examples with further references there.

I would rather use some acid other than FeCl3 for this reaction. In most cases it tends to give dirtier products than AlCl3 in Friedel-Crafts acylations, so I would guess it would give a dirtier product also in a retro-Friedel crafts alkylation of an acylbenzene.

johnames - 13-3-2011 at 13:27

Use another acid as in use AlCl3 instead? I also found a few examples using sulfuric acid as well as phosphoric acid (I use 85% phosphoric for Boc deprotections). Maybe acetic acid as solvent, anisole as receiver and sulfuric acid or phosphoric acid would do the trick.

[Edited on 13-3-2011 by johnames]

spirocycle - 13-3-2011 at 13:57

^it is not t-BOC deprotection.
you cant compare the conditions indiscriminantly

johnames - 13-3-2011 at 14:02

I understand that, but I found examples of dealkylation of benzene using 85% phosphoric acid. I was just commenting that I also use 85% phosphoric acid for Boc deprotections. Example of dealkylation in phosphoric acid can be found in the reference Nicodem posted, don't have access to the article though so can't post it.

spirocycle - 13-3-2011 at 14:50

ok gotcha, misunderstanding

johnames - 13-3-2011 at 17:11

I finally found the review Nicodem is talking about, it is attached. Looks like AlCl3 in toluene/xylene is common, efficient, and high yielding. I haven't found much on why FeCl3 leads to dirtier products. Can you expand on this Nicodem?

Attachment: s-1979-28876.pdf (1.7MB)
This file has been downloaded 483 times

johnames - 13-3-2011 at 20:54

Going to do side by side runs of FeCl3/toluene and sulphuric acid/anisole/acetic acid first. If nothing works out I will try the standby AlCl3/toluene. FeCl3/toluene will be washed with cold water and then vacuum distilled to yield final product. Sulphuric acid/anisole/acetic acid run will be extracted with CH2Cl2, washed, and vacuum distilled to yield final product.

Should I post results in this thread or the Organic Chemistry section? Any tips/advice would be appreciated.



[Edited on 14-3-2011 by johnames]

[Edited on 14-3-2011 by johnames]

Nicodem - 14-3-2011 at 05:17

Quote: Originally posted by johnames  
I haven't found much on why FeCl3 leads to dirtier products. Can you expand on this Nicodem?

Not much to expand. Like I said, my limited experience with FeCl3, based on few uses, is in that it leads to dirtier products in acylations when compared to AlCl3. It does not mean that this is generally true, or that it is true also for the dealkylation you want to use it for.
Otherwise, your proposed parallel runs sound reasonable to me. Though sulfuric acid in acetic acid efficiently catalyses the aldol condensations, so you might expect some troubles with these kind of side products given that your substrate is a ketone.
Quote: Originally posted by johnames  
Should I post results in this thread or the Organic Chemistry section? Any tips/advice would be appreciated.

If you are going to do such comparative tests and are willing to write a short report with some minimal analytical data and used references, then the Prepublication section is the place to post experimental results. I'm sure there are chemists who will find your experience valuable. On the other extreme, if you don't feel like it, or are in a lazy mood, you can always just post a comment on your results in this thread. Anything will be appreciated, though the more you give the more it is appreciated.