Sciencemadness Discussion Board

Clarification needed about Friedel Craft Reactions mechanism/catalytic requirement

FireLion3 - 22-7-2014 at 18:06

I've only read about and briefly studied these reactions, but I was looking to experiment with some of them soon. I just have one problem. Almost every source I encounter says something different about whether a stochiometric amount of catalyst is needed. Some sources say a stochiometric amount is needed for the Acylation, others say it is for the Alkylation, a few say it is needed for both, and a number show diagrams saying the catalyst regenerates in both the Acylation and Alkylation!!!

What!! As I understand it the catalyst is consumed when the the catalyst complexes with the product...? But how does this relate to whether the reaction is an acylation or an alkylation?

Also, I ran into a number of sources saying the reaction must be anhydrous. Some sources said it was just because some of the stronger lewis acids react with water. Other sources said that [a large number of] hydrated lewis acid salts can be used in water, with more effective yields coming from the utility of phase transfer catalysts - though, the strength of the lewis acid will directly effect the rate of the reaction.


Can anyone who has experience with these please clarify? Does catalytic vs stochiometric quantities of catalyst depend solely on the reagent? Or the catalytic cycle unique to each reaction? I'm mainly interested in the alkylation, and looking at that, it appears that the catalyst is recycled, but I have no clue about the idea of it being deactivated by complexing with the product.

UnintentionalChaos - 22-7-2014 at 18:48

FC reactions are generally water-intolerant as long as you're using a halide-derived carbocation source. In some cases, you can use something like tert-butanol and sulfuric acid to generate the relatively stable t-butyl carbocation in water/acetic acid/etc as long as you have a highly activated benzene ring to trap it. FC alkylation can be sub-stoichiometric, but more typically makes it go faster and AlCl3 is cheap, since you lose HX as a gas on reaction and the finished product is just an alkane

FC acylation is not truly catalytic. The finished ketone is a lewis base and binds an equivalent of catalyst rendering it inactive for further reaction. When using acyl halides, ~1.2eq of AlCl3 is typical. Acid anhydrides raise a further problem in that the byproduct carboxylic acid binds an additional equivalent of AlCl3, 2.2eq is typically used. Neither acyl halides nor anhydrides are water-tolerant.

FireLion3 - 22-7-2014 at 19:11

So the alkylation can generally be done with catalytic amounts, but the reaction time will generally be longer?

What is the specific reason for water intolerance (besides some lewis acids reacting with water). Is it because the water solublizes the lewis acid into a different phase? Or does the carbocation react with water; I can't imagine this be a problem if the phases are separated.

Searching Friedel Crafts Alkylation and Phase Transfer Catalyst seemed to turn up a number of results. This could potentially be effective if both reactants are water immiscible.

UnintentionalChaos - 22-7-2014 at 19:33

Quote: Originally posted by FireLion3  
So the alkylation can generally be done with catalytic amounts, but the reaction time will generally be longer?

What is the specific reason for water intolerance (besides some lewis acids reacting with water). Is it because the water solublizes the lewis acid into a different phase? Or does the carbocation react with water; I can't imagine this be a problem if the phases are separated.

Searching Friedel Crafts Alkylation and Phase Transfer Catalyst seemed to turn up a number of results. This could potentially be effective if both reactants are water immiscible.


Lewis acids like AlCl3 and FeCl3 are destroyed by water. The anhydrous compound has electron-withdrawing metal-halide bonds and empty orbitals to accept lone pairs from lewis bases. Add water and you get a metal ion bound to several water molecules which are effective lewis bases. (often octahedral geometry) and the halides are just counterions in solution.

FireLion3 - 22-7-2014 at 20:07

Quote: Originally posted by UnintentionalChaos  
Quote: Originally posted by FireLion3  
So the alkylation can generally be done with catalytic amounts, but the reaction time will generally be longer?

What is the specific reason for water intolerance (besides some lewis acids reacting with water). Is it because the water solublizes the lewis acid into a different phase? Or does the carbocation react with water; I can't imagine this be a problem if the phases are separated.

Searching Friedel Crafts Alkylation and Phase Transfer Catalyst seemed to turn up a number of results. This could potentially be effective if both reactants are water immiscible.


Lewis acids like AlCl3 and FeCl3 are destroyed by water. The anhydrous compound has electron-withdrawing metal-halide bonds and empty orbitals to accept lone pairs from lewis bases. Add water and you get a metal ion bound to several water molecules which are effective lewis bases. (often octahedral geometry) and the halides are just counterions in solution.


Are you specifically referring to those lewis acids that are destroyed by water? There are a number that aren't destroyed by water and can maintain their lewis acidity in said water that work for friedel crafts (according to studies), though are less strongly activating. Though, I haven't done enough reading to know if they work IN water for Friedel Crafts.

I've got a small amount of NiCl2 laying around that I read could work, but I need to do more reading into it.

blogfast25 - 23-7-2014 at 09:06

Quote: Originally posted by FireLion3  
I've got a small amount of NiCl2 laying around that I read could work, but I need to do more reading into it.


Your NiCl2 is likely to be a hydrate, in which case it cannot work as a Lewis acid.

arkoma - 23-7-2014 at 09:15

Nickel salts are so toxic/carcinogenic. Careful.

FireLion3 - 23-7-2014 at 13:47

Quote: Originally posted by blogfast25  
Quote: Originally posted by FireLion3  
I've got a small amount of NiCl2 laying around that I read could work, but I need to do more reading into it.


Your NiCl2 is likely to be a hydrate, in which case it cannot work as a Lewis acid.


I know NiCl2 Hydrate can work as a lewis acid in many cases, but you may be right about the hydrate preventing it from working in a FC.

I might could probably dry it pretty easily, though, I should just go ahead and order myself some AlCl3. If it can be used in catalytic quantities then I don't really have an issue.

Quote: Originally posted by arkoma  
Nickel salts are so toxic/carcinogenic. Careful.


Thanks for looking out.

A large number of transition metal salts fit this profile, but they're not typically volatile, and unless you have a hurricane blowing through your lab, they're certainly not going to go flying into the air when you can inhale them if they are in their hydrated form. I've probably suffered more brain damage from all of the solvent fumes I've inhaled by being around them than the large quantities of transition metal salts I've handled - properly and with gloves mind you.

blogfast25 - 24-7-2014 at 08:19

Quote: Originally posted by FireLion3  
I know NiCl2 Hydrate can work as a lewis acid in many cases, but you may be right about the hydrate preventing it from working in a FC.



Got any references for that?

In hydrated NiCl2 the Ni is present as the nickel hexaaqua cation. That's not a Lewis acid because it can't accept any electron pairs. Although ligand exchange might be possible.

arkoma - 24-7-2014 at 08:36

Well, I am sort of thinking that MAYBE, theoretically, some of these products MIGHT end up being consumed by human beings--why I cautioned about the NiCl. Kind of nasty stuff to inadvertently have any remaining in a finished product.

FireLion3 - 24-7-2014 at 19:25

Quote: Originally posted by blogfast25  
Quote: Originally posted by FireLion3  
I know NiCl2 Hydrate can work as a lewis acid in many cases, but you may be right about the hydrate preventing it from working in a FC.



Got any references for that?

In hydrated NiCl2 the Ni is present as the nickel hexaaqua cation. That's not a Lewis acid because it can't accept any electron pairs. Although ligand exchange might be possible.


A ligand exchange would be the only way, I would think The majority on my research into NiCl2 was its usage within phosphine coordination complexes. Forming these complexes do not require the anhydrous salt, but apparently the reaction mixture must be relatively anhydrous. Phosphines themselves are much more nucleophilic than water. This is research reading I had done 3-4 months ago, so my memory is fuzzy on it. I just remember reading a ton of articles speaking on how NiCl2 and other mild lewis acids can be used to the slight activation of carbonyls, as well as forming electrophilic complexes in situ with hypohalous acids to enhance their reactivity, among other things.

In any case, I think it is an undeserved assumption to assume the water ligands totally block the lewis acidity, in some cases though, absolutely. While taken with a grain of salt, I remember coming across a Hive link in my readings that spoke of NiCl2 Hydrate being used as a mild lewis acid in FC alkylations, to which the author assured this with his own prior experiments, though, if this were true I would presume its activity be much lower than traditional "strong" lewis acids such as FeX3 and AlX3
Quote: Originally posted by arkoma  
Well, I am sort of thinking that MAYBE, theoretically, some of these products MIGHT end up being consumed by human beings--why I cautioned about the NiCl. Kind of nasty stuff to inadvertently have any remaining in a finished product.


You talk about this stuff like it could kill a heard of elephants. There are far nastier things that go into the production of human consumed products that are hundreds of times more toxic. I wouldn't say it is any more of a concern than the incredibly toxic (and extremely volatile) Mercury Halides that are all too popularly used in Amalgams.

In any case, without proper purification, most crude products intended for human consumption are going to have some residual unpleasant compounds. Though, these are usually nothing simple work ups won't take care of.

arkoma - 24-7-2014 at 19:48

Quote:

You talk about this stuff like it could kill a heard of elephants. There are far nastier things that go into the production of human consumed products that are hundreds of times more toxic. I wouldn't say it is any more of a concern than the incredibly toxic (and extremely volatile) Mercury Halides that are all too popularly used in Amalgams.

In any case, without proper purification, most crude products intended for human consumption are going to have some residual unpleasant compounds. Though, these are usually nothing simple work ups won't take care of.


*arkoma bows and sez, "touche"*

Firelion, you seem pretty sharp--refreshing actually.

FireLion3 - 24-7-2014 at 21:47

Quote: Originally posted by arkoma  
Quote:

You talk about this stuff like it could kill a heard of elephants. There are far nastier things that go into the production of human consumed products that are hundreds of times more toxic. I wouldn't say it is any more of a concern than the incredibly toxic (and extremely volatile) Mercury Halides that are all too popularly used in Amalgams.

In any case, without proper purification, most crude products intended for human consumption are going to have some residual unpleasant compounds. Though, these are usually nothing simple work ups won't take care of.


*arkoma bows and sez, "touche"*

Firelion, you seem pretty sharp--refreshing actually.


I hope that is a compliment and not an sarcastic insult :D.

I do appreciate you looking out for me though with regard to toxic compounds. I am generally fairly careful when I handle compounds. I absolutely refuse to touch anything without gloves, and I usually throw on two pairs if they are prone to ripping. Last thing I need is the tip of a glove ripping without me knowing and having one single finger exposed to something toxic, only to realize it an hour later. I generally avoid breathing in any solvents when I can, and am super delicate with fans off when working with any light and fluffy powders.

Have you ever smelled Tetrabutylammonium iodide? It is much more unpleasant smelling than its cousin CTAB. It's not the worst smelling thing but it has an annoying knack to leave quite an unpleasant odor in your noses and on anything it touches. Effective, but nasty smelling.

arkoma - 25-7-2014 at 10:20

it is MOST DEFINITELY a compliment--I admit I was "suspicious" of you at first, not that I am against the chemistry of biologically active compounds...........

aga - 25-7-2014 at 11:37

Quote:
an unpleasant odor in your noses

This is one way we catch you Aliens.

Humans only have one Nose.
M.I.B. notified.

The Gloves thing reminds me of Prof Wetterhahn.
DimethylMercury. 2 drops on Latex gloved hands.
Died 5 months later.


[Edited on 25-7-2014 by aga]

blogfast25 - 26-7-2014 at 06:00

Quote: Originally posted by FireLion3  
[...] though, if this were true I would presume its activity be much lower than traditional "strong" lewis acids such as FeX3 and AlX3



Exactly. In most FCs hydrated NiCl2 will be a very poor choice.

FireLion3 - 26-7-2014 at 12:11

Quote: Originally posted by blogfast25  
Quote: Originally posted by FireLion3  
[...] though, if this were true I would presume its activity be much lower than traditional "strong" lewis acids such as FeX3 and AlX3



Exactly. In most FCs hydrated NiCl2 will be a very poor choice.


Though, what of its properties on an anhydrous basis?

I recently found a large amount of Zinc Sulfate Hydrate at a local store. I can't imagine it would be difficult to dehydrate with some heating. A few google searches revealed it was a lewis acid, with one site even claiming, quote, "strong lewis acid".

I may be curious enough to experiment with this sometime. If it proves effective, that would be quite interesting that it can be picked up at the store.

blogfast25 - 27-7-2014 at 03:35

Quote: Originally posted by FireLion3  

Though, what of its properties on an anhydrous basis?



FC alkylation catalysis relies on Cl's ability to ligand with the catalyst: that's something AlCl3, FeCl3 and SnCl4 are good at doing. Ni and Zn much less so, I think. You might want to consider anh. CuCl2, which is easy to prepare and of which at least we know that it forms tetrachloro cuprate anions (in aqueous media) quite enthusiastically.

SnCl4 can be prepared quite easily, even without directly chlorinating tin, see my work on that starting from K2SnCl6:

http://www.sciencemadness.org/talk/viewthread.php?tid=29645#...

[Edited on 27-7-2014 by blogfast25]