Sciencemadness Discussion Board - Friedel-Crafts acylation

Friedel-Crafts acylation

Magpie - 2-4-2010 at 16:43

Yesterday I performed this named reaction to obtain a small amount of acetophenone. The acylating agent was acetic anhydride. Lewis acid was anhydrous AlCl3. Following Brewster my set-up included a safety trap and an inverted funnel over water to capture HCl gas.

During cleanup I inadvertantly got a whiff of the gas in the safety trap. It was indeed HCl! My question is: how is this HCl generated, ie, by what mechanism?

Note: I understand where the acetic acid byproduct comes from, just not the HCl.

[Edited on 3-4-2010 by Magpie]

[Edited on 3-4-2010 by Magpie]

entropy51 - 2-4-2010 at 17:26

Congratulations, Magpie! You have confirmed the mechanism of Friedel-Crafts acylation.

They do indeed give off HCl, the reason Brewster calls for a trap.

Magpie - 2-4-2010 at 17:47

This is the reaction stated by Brewster, Exp 66:

C6H6 + Ac2O ---> C6H5COCH3 + CH3COOH

with no HCl by-product indicated.

I presume the mechanism includes -OOCCH3 bonding to the AlCl3, which then breaks down to CH3COOH after receiving a proton from the phenyl ring. If this is true where does the HCl come from?

I'm probably oversimplifying the mechanism and the AlCl3 complex breaks down to some HCl also?

Nicodem - 3-4-2010 at 00:59

It is the reaction of AlCl3 (actually AlCl3 coordinated with organic reaction components) with the protic reaction products, in this case mostly acetic acid. In their interaction AlCl3 is an acid and acetic acid is a base (speaking about their interaction roles - not relative to their reaction with H2O as a base, as the acid/base terms are commonly used). Their acid/base reaction is:
MeCOOH + AlCl3 <=> H[AlCl3(OOCMe)]
However, H[AlCl3(OOCMe)] can dissociate also in another way:
H[AlCl3(OOCMe)] <=> AlCl2(OOCMe) + HCl

Of course, this is just a terrible simplification of a solvolysis reaction of AlCl3. All these species are involved in numerous equilibrium relationships and true solvolyses are by definition terribly promiscuous reactions and very hard to frame in simple equations and simply defined species (in solvolyses the solvent is always everywhere and always involved). Here the difference is in the dilution of MeCOOH.
In short, AlCl3 reacts quite readily with protic basic enough solvents and even though acetic acid is much less basic than water (where AlCl3 solvolyses/hydrolyses completely), some solvolysis nevertheless occurs with carboxylic acids as well. Usually you only notice this when HCl escapes from the system as a gas, because otherwise reversibility is granted by the equilibrium constants.

You can make a simple experiment (on a small scale!). Add some AlCl3 to each glacial acetic acid, ethanol and water (carefully!). HCl is soluble in all these solvents, so besides some exotherm, there should not be much gas evolution. Then try the same using diluted solutions of acetic acid, ethanol and mixture of H2O in some nonpolar solvent where HCl is not particularly soluble (CH2Cl2, hexane...). Use 1:1 ratio of AlCl3 vs. base (MeCOOH, EtOH, H2O). You should notice the HCl gas evolution it is all about its solubility and that is actually the only reason why you even noticed it.

[Edited on 3/4/2010 by Nicodem]

Magpie - 3-4-2010 at 07:46

Nicodem thank you for that detailed explanation! I can see now why the subject was just not brought up in the references I consulted.

Magpie - 4-8-2015 at 16:10

I recently made acetophenone using the procedure in Vogel’s 3rd (forum library). Vogel stated that the expected yield was 27g. All I managed to get was 11.7g. Here’s some pictures from this experiment:

Addition of acetyl chloride

Attachment: phpD693Wv (89kB)
This file has been downloaded 1169 times
55° hold for 1 hour

Rxn product acetophenone (colored with tar)

1st water separation - acetophenone.jpg - 72kB

5% caustic wash separation

2nd water separation - acetophenone.jpg - 69kB

Water wash separation

Benzene recovery

Aceotophenone coming over at 200°C

Discussion
This is the 3rd Friedel-Crafts acylation that I have done. The 1st was to make p-methylacetophenone from toluene in a school lab. The two others were done in my lab.

Attached is an EXCEL spreadsheet comparing the 3 runs. The first procedure is clearly superior in that the yield is much higher at 79%. Based on these results I will be using high ratios of AlCl3 and acylating agent for any of my future runs. I don’t see how Vogel managed to get such a high yield, 60.8% based on the acylating agent.

Attachment: Friedel-Crafts comparisons of yield.xls (23kB)
This file has been downloaded 537 times

Please share the experiences you have had running Friedel-Craft acylations, especially with regard to yield efficiency.

AvBaeyer - 4-8-2015 at 18:11

Magpie,

With regard to yields reported in Vogel: This book is simply an aggregation of syntheses and procedures reported elsewhere, such as Organic Syntheses. So the yields reported in Vogel depend on where the author obtained the procedure. I have found on several occasions that yields reported in Vogel are often hard to match. Don't misinterpret me though regarding the book's overall value. Vogel is an excellent reference with lots of clearly organized information.

And as usual, your work is very nicely reported and something I always look forward to reading.

AvB

Magpie - 4-8-2015 at 19:29

Thank you AvBaeyer.

I feel chagrined that I just now noticed the fine write-up of Mercedesbenzene in Prepublication. There he reports an efficiency of 71.8% on acetic anhydride using a Vogel procedure.

--------------------------------------------------------------------------------

For comparison I added the results of Mercedesbenzene to my EXCEL spreadsheet. His parameters do not show high ratios of AlCl3 and acylating agent to the substrate. I now believe that his meticulous attention to water exclusion and purity of benzene gave his high yield.

Attachment: Friedel-Crafts comparisons of yield.xls (23kB)
This file has been downloaded 524 times
----------------------------------------------------------------------
I now think that there is a good chance that the low yields I show on my spreadsheet were due to poor quality AlCl3. I was using it out of my old Daigger bottle. I had replaced this with a bottle from Elemental Scientific which performed very well when I made benzophenone (72.3% yield). But the Elemental supply was ruined due to water vapor permeation through the plastic container so it had to be disposed (that was quite an ordeal in itself). So I used the Daigger supply, forgetting why I had replaced it in the first place!
[Edited on 5-8-2015 by Magpie]

[Edited on 5-8-2015 by Magpie]

softbeard - 6-8-2015 at 09:14

Quote: Originally posted by Magpie

I now think that there is a good chance that the low yields I show on my spreadsheet were due to poor quality AlCl3.

Yes, shame about water-permeation ruining your AlCl₃. This has probably been answered many times, but would AlBr₃ or AlI₃ also work for Friedel-Crafts? Perhaps AlBr₃ or AlI₃ could be prepared in-situ by reacting Al metal and the halogen; possibly in a suitable inert solvent (like a saturated hydrocarbon, eg. hexane). Then you could be pretty sure your AlX₃ is anhydrous.

Magpie - 6-8-2015 at 12:29

The AlCl3 (250g) I had bought from Elemental Scientific was excellent material, very active. I used it for making benzophenone shortly after receiving it, and it was "dynamite."

I had the bottle protected by 4 layers of plastic. The 1st layer was heavy plastic as supplied by Elemental. In the outer bag I had placed some NaHCO3. Then it sat in my garage for ~ 6 months before I attempted to use it to make some acetophenone. This is when I discovered that it had been ruined by atmoshperic moisture permeating the plastic bottle in which I received it. I live in a dry climate. The bottle barely had any integrity left and it had turned black contaminating the AlCl3.

For disposal I filled a 5-gallon plastic bucket with water and ice-cubes. Then, in my hood, I slowly added the AlCl3 powder, a spoonful at a time, stirring with a wood stick. This was a slow, noxious job as the AlCl3 still packed quite a wallop. A lot of nasty fumes were generated.

I will be getting a new supply of AlCl3 from Elemental. I hope it comes in a better container - a glass jar seems best. But there is still the matter of the lid and seal materials being vulnerable.

AvBaeyer - 6-8-2015 at 13:44

I applaud Elemental for being able to supply many extremely useful reagents. Unfortunately, they make far too much use of poorly sealing plastic containers which obviously helps with shipping costs. I transfer most things I receive from them into quality glass bottles with good sealing properties upon receipt.

I have used aluminum chloride in the past (when I was gainfully employed) from very old but well sealed glass bottles. These bottles were sealed with many layers of Parafilm or had been dipped in wax. Sometimes the AlCl3 had a bit of yellow tinge but never black and always worked as intended. I do not think going to the trouble of making the triiodide or tribromide is worth the effort.

AvB

clearly_not_atara - 9-8-2015 at 11:04

Quote:

This has probably been answered many times, but would AlBr3 or AlI3 also work for Friedel-Crafts? Perhaps AlBr3 or AlI3 could be prepared in-situ by reacting Al metal and the halogen; possibly in a suitable inert solvent (like a saturated hydrocarbon, eg. hexane). Then you could be pretty sure your AlX3 is anhydrous.

Two problems occur to me: first, a lot of heat is generated by this reaction (boiling the relevant halogen); second, the aluminum must be activated in the absence of oxygen. Most nonpolar solvents will catch fire during this reaction; you might be able to react small amounts of Al with Br2 in chloroform.

FriedBrain - 10-8-2015 at 02:05

Well, what a shitty first post, just deletetd it by an accident...
Another try:
I would suspend your Aluminium (I think as a FC catalyst Aluminiumfoil should be suitable) in a solvent like chloroform, that is inert (don't forget that hydrocarbons will react a little bit, because of radical bromation). Then through an addition Funnel a solution of bromine in chloroform is slowly added dropwise in your ice cooled and well stirred reaction mixture. Even if the bromine should react immediatly and higher temperature should not accure, i would use an reflux condensor just to be safe.
Because I can't estimate the reaction of a dilute bromine solution with a suspension of Aluminium in chloroform, i would at first test it, so there will be no surprise of something like any fire appearence.
For aluminium iodide as a FC catalyst I'm suspiciousm, but it's a try worth!
And because the storage and handling of anhydrous AlX₃ is kind of shitty (fuming of HCl and it gets bad), the way discribed could be a good way to get the catalyst right in your reaction flask.
And here is a post about right this topic @beginnings: http://www.sciencemadness.org/talk/viewthread.php?tid=63269

Loptr - 10-8-2015 at 08:20

Quote: Originally posted by Magpie

The AlCl3 (250g) I had bought from Elemental Scientific was excellent material, very active. I used it for making benzophenone shortly after receiving it, and it was "dynamite."

I had the bottle protected by 4 layers of plastic. The 1st layer was heavy plastic as supplied by Elemental. In the outer bag I had placed some NaHCO3. Then it sat in my garage for ~ 6 months before I attempted to use it to make some acetophenone. This is when I discovered that it had been ruined by atmoshperic moisture permeating the plastic bottle in which I received it. I live in a dry climate. The bottle barely had any integrity left and it had turned black contaminating the AlCl3.

For disposal I filled a 5-gallon plastic bucket with water and ice-cubes. Then, in my hood, I slowly added the AlCl3 powder, a spoonful at a time, stirring with a wood stick. This was a slow, noxious job as the AlCl3 still packed quite a wallop. A lot of nasty fumes were generated.

I will be getting a new supply of AlCl3 from Elemental. I hope it comes in a better container - a glass jar seems best. But there is still the matter of the lid and seal materials being vulnerable.

The 1kg listing of AlCl3 they sell seems to come in a glass bottle, or at least mine did. I also store it in a paint can filled with calcium chloride. It still generates some positive pressure and when I open the paint can a cloud of vapor comes out, but it is still very reactive and white.

chemrox - 10-8-2015 at 10:28

The AlCl3 sits happily in the hood but the PCl5 is another story. I put the bottle in the fridge to limit exposure to moisture. This isn't working judging from the nasty white crust around the bottle cap. I'm going to get some paraffin, displace any air with Ar and make a wax seal around the top.

Magpie - 10-8-2015 at 10:30

Quote: Originally posted by chemrox

.... I'm going to get some paraffin, displace any air with Ar and make a wax seal around the top.

Sounds like a good idea.

FriedBrain - 11-8-2015 at 01:25

A wax seal, sounds interesting. Do you just melt the candles (or any other wax sources) in a container and then dip the top of your container in it? I'm sceptical about the thightness auf this seal, I always used "Parafilm" if you know that, but my anhydrous Aluminiumchloride always diffuses some HCl through it.
I would appreciate it, if you could make some photos of your seal!

[Edited on 12-8-2015 by FriedBrain]

Magpie - 10-8-2016 at 18:48

I recently prepared acetophenone using 2 different procedures, ie, Brewster and Vogel (1.5X).

The Brewster procedure was small scale: 11.0g, 46%. The Vogel procedure was larger scale: 40.8g, 89.2%.

See yield comparison spreadsheet below:
Attachment: Friedel-Crafts comparisons of yield.xls (24kB)
This file has been downloaded 485 times

I was encouraged to try the Vogel procedure based on the high yield of Mercedesbenzene's preparation. His preparation is shown in Prepublication and is based on a 1.5X scale of the Vogel procedure.

My preparation followed Vogel except I used 100mL of CH2Cl2 to extract the aqueous phase instead of using ether. This was a little tricky as I ended up with aqueous and organic phases that were close in density. This wouldn't happen with ether.

Also, for the quench I used much more water/ice than Vogel. I probably used about 650g total. As Mercedesbenzene emphasizes the quench is violent and must be done slowly with great caution.

My AlCl3 was a little messed up due to degraded plastic contamination from to a failed AlCl3 jar lid. But it didn't hurt my yield much, IMO.

There was significant interfacial crud during the washes. I removed this during the final wash with water.

Comments, questions, and suggestions are welcomed.

distilling off the DCM and benzene

acetophenone yield

Edit: I dried my benzene with CaCl2 and 3A mol sieves, but no other purification. I used a mechanical overhead stirrer.

[Edited on 11-8-2016 by Magpie]

[Edited on 11-8-2016 by Magpie]

Acylation of 1,4-Dimethoxybenzene

aab18011 - 6-12-2021 at 00:55

Just ran an acylation of 1,4-Dimethoxybenzene (DMB) to afford 2,5-dimethoxyacetophenone from Ac2O, AlCl3.

This was done small scale as I only had 320mg exactly of DMB, done in a test tube.

I used DCM as the solvent in hopes that it would help keep some oxygen out with its vapors.

Heres the notes:

Directly from my notebook, "320 mg of DMB (0.002316 mol) + 250 mg of Ac2O (0.002450 mol or 0.2316 mL) + 679 mg of AlCl3 (0.005095 mol) + 3.5 mL of DCM (1.2mL for Ac2O and 2.3mL for main mixture)" for the exact amounts used. My scale is calibrated with 100 g and is accurate to 0.01g increments. The scale has become somewhat off since my 100g calibration weight was found to be closer to 98.78g on my university scales.

Now I followed a procedure found from a university, the experiment was the acylation of anisole (methoxybenzene), and I assumed that the properties of the compounds would allow this to work fine.

Here is the link to the website: North Central College Chemistry

In this order:
- I added in DCM (I dried the DCM quickly over MgSO4) and quickly measured and added the AlCl3.
- Next I dropped the two DMB crystals in and quickly shook the tube by flicking and swirling. By this point, the tube turned orangy-yellow.
- After measuring the weight of Ac2O, I added in DCM quickly to avoid evaporation.
- Slowly I added the Ac2O mixture with little to no effect. By this point the tube was turning brown, but with a weird yellow/green color. The yellow/green couldn't be seen unless refluxing which allowed bubbles to form, which took on the color. The solution itself resembled a sort of FeCl3 color. I didn't suspect FeCl3 to be in my AlCl3 considering I got it from a good company (a friend gave me some Sigma AlCl3).
- After addition, I got a hot water bath going with a small beaker of water and began heating until reflux, for approx. 30 min.
- The solid AlCl3 began to dissapear and HCl was evolving off the tube in a decent but small quanitity. There was still smell of DMB but much less than before. By 20 min the smell of DMB was very minute but still present and all the AlCl3 was pretty much gone, unless the tiny bits left over were some salt or otherwise. After 2 NaOH and 2 NaCl washings, the DCM and 2,5-dimethoxyacetophenone was dried over MgSO4 and then filtered and boiled down in the containing vial. After complete boiling down to the almost pure product, the final weight was 120mg which is approximately 28.8%.

In hindsight, I am assuming that the low yield was due to absolute fuck all control and possibly impatience during separations. However, I feel that for almost no care given for this reaction, the 28.8% yield suggest the AlCl3 ratio as discuss in earlier posts warrants serious attention.

If any DMB is left over, then it is definitely within the liquid product which is very similar in structure and therefore probably has some ability to dissolve each other. No crystals came out after boiling out the DCM.

Also something weird I noticed is that the ice/water quench was not nearly as violent which leads me to believe that either my DCM and/or my Ac2O was very wet with moisture from the air. So I will try to distil them fresh and let them sit in a container over sieves/salts to dry.

As a final note, I am going to try this again with a different reagent since that was all I had, as well as get an IR and possibly an NMR for this product, if my professor is in a good mood of course.

EDIT: added the image of the IR result