Chem Question (Friedel Crafts Reactions)

Heya all.
Firstly to the mods, if this is irrelavent to this forum or too technical or the such, delete/move it and I won't mind, my organic chem lecturer has gone on holiday and I'm hoping someone out there in Bluelight land can help...
Okay, now that's out of the way... The question.
I was sitting down on a Sunday afternoon, reading about the wonderful abilites of benzene rings and the substituents (as you do ) when I came across the Friedel-Craft reactions (aromatic electrophillic substitutions.) What I found out is that when you add an electrophile to a benzene ring in an electrophillic substitution, it sometimes rearranges itself to become a more stable carbocation before joining with the ring. (For example, a hydrogen or alkyl group shifts position in the molecule to be able form a teritary carbocation instead of a primary, say 2,2 dimethyl-propyl shifts one of its methyl groups to turn the carbocation into 1,2 dimethyl-propyl) Now, if this was to happen in a lab where making something where postion of the carbons is quite important, say... LSD, the result would be an inactive compound.
So, my question is, is there any way to completely prevent this carbocation shift? All the sources said was that these shifts are dependant on temparature, catalysts, and solvents used, but didn't elabourate.
Can you stop it, or do you just have to grin and bare it and remove the undesirable compounds at the end of the reactions?

pity cant help
but i shouldn't have dropped / failed chem sounds like it gets better than boring old acid / base shit

I have no idea what you just said, but there'll be people out there that do so the thread's cool...
There are some bees out there that have a forum similar to this that would know the answer though (you might already be familiar with it) - however I can't post the link unfortunatly cos it's against the rules...
Check your email! :D
[ 11 June 2002: Message edited by: Pleonastic ]

In short yes and no. Depends entirely on your choice of catalyst etc., and the particular reaction.
You may already have done this. I’ve likely gone over a bit of what you’ve studied so bear with me. First of all look at the relative stability of alkyl cations.
Me3C+ > Me2CH+ > MeCH2+ > CH3+.
Therefore such a rearrangement as you mention should not be energy favourable as the cation is already trisubstituted. The trick is that when the initial electrophillic complex forms, it is polarized enough to allow rearrangement to the more stable (1,2 alkyl -halide- Lewis acid) intermediate complex. Therefore the strength of the Lewis acid affects the outcome. As you said temperature is a factor and may supply the additional energy needed to cause rearrangement. An Alkyl Chloride and AlCl3 may not require any heat at all. However this doesn’t explain a mixture of products often found.
Sykes; 'Mechanism in Organic Chemistry’ page 142 sheds a bit of light, explaining –
“The actual proportions of products obtained in many cases are not necessarily found to reflect the relative stabilities of the incipient carbocations, un-rearranged and rearranged, however. This follows from the fact that their relative rates of reaction with the aromatic species almost certainly do not follow the order of their relative stabilities, and may well be diametrically opposed to it. Attack on the aromatic species by the first formed polarized complex may be faster than its rearrangement. The study of these rearrangements is also complicated by the fact that Lewis acids are found to be capable of rearranging both the original halides and the final alkylated end products….”
For the reasons listed above Friedel Craft alkylations can be of limited application in many syntheses. If a chemist were to do such a reaction, he would consult the literature where possible and perhaps look for a different approach, say to start with an already substituted molecule and merely alter the functional group.
As you are no doubt aware, electrophilic substitution on a 6 carbon aromatic ring already di-substituted ie adding another group to another place on the ring, can be extremely difficult if not impossible without the appropriate directing activator. This is where retrosynthesis comes in; disassembly of the target molecule by anions and cations. Often this reveals there are several routes available, but usually 1 or 2 are obviously easier. The final chosen synthesis may be based on expected yields and available precursors.
That being said there are certain deactivating substitutes which readily accept another substitution because of some special characteristic of the molecule. This may be due to any or all the factors mentioned; cation stability, nature of the catalyst etc and others such as steric repulsion and photochemical or cycloaddition reactions. The chemist won’t assume the retrosynthesis determination to be the correct choice unless he is either familiar with the routes or has checked the literature. Organic chemistry is full of anomalies, and sometimes what shouldn’t work actually does, but more often than not it’s the other way round. The alchemy of the art still prevails, but doesn’t stop the physical chemists from attempting to unravel its mysteries.
Nitrostyrenes intermediates, grignards, aldol, wittig, etc etc., are such versatile tools, often with known end product ratios. These reactions are performed routinely in the lab and industry( although wittig is gradually being replaced in industry as it produces lots of waste)
I can’t imagine any chemist wanting to alkylate benzene, when you could start with a benzyne cation, I could be wrong though. I’ve never been able to figure out how they make 1,2,4,5 tetrafluorobenzaldehyde, used in the production of a synthetic pyrethroid.
Be careful with the busy bee place pleo mentions. It has a habit of flaming you like no other if you post without either completely knowing what you are talking about or not Using TFSE first. Good luck though, there are few better place to learn chemistry, and not only drug related….oops bit too much of a promotion….err… I withdraw that last statement
[ 11 June 2002: Message edited by: phase_dancer ]

^ : Great post Phase_dancer, thanks!
BigTrancer

Thanks phase_dancer!
Yes, there was stuff I've been through before, but there were some gems that I've taken note of. We don't really get into many mechanisims of reaction until our final year. Oh well.
There was a simple answer to my quandry that you brought to my attention: If you want to introduce an akyl group to a benzene (subsituted or otherwise) without a carbocation relocation, don't use a Friedel-Crafts reaction. Use another mechanisim. I guess I should've paid more attention in class, hey?
I've started buzzing through the site that was mentioned... It's a treasure trove of chemical knowledge.
(guess what I'm gonna be reading on the holidays.)

Fetish Jester. I'm not sure what course you're doing but I assume there is a large chemistry component. In regards to mechanisms, if you are doing 2nd and 3rd year organic, there are a couple worth learning now. I knew quite a few bright people who failed the subjects 1st time round simply because they struggled with some mechanisms.
First and foremost are aldol and claisen condensation reactions. Work from simple things like acetone, up to ethyl acetoacetate and diethyl malonate, then mixed aldols. You’ll learn how complicated molecules can be made from just ethanol!
After you get this, go on to Michael and Robinson reactions. These make cyclic compounds from the aldol products. You'll feel like a real chemist when you grasp this, for me it unraveled many mysteries.
Learn how the electrons move, each step down to dehydration of the unsaturated ketones.
Practice the reactions until you can look at any simple carbonyl compound and picture the end products of condensation. They aren't hard really, but like the ligand field theory I'm doing now, practice is everything.
Of course there are heaps of others you will have to learn, just as complicated and more so, but many chem students have found aldol to be a quantum leap in difficulty.
Other essentials include diels alder, wittig, and amide chemistry; and take a look at subjects such as electrocyclic reactions. If you have Mc Murray, 'Organic Chemistry' these subjects are quite well covered. Add hydride reactions, but check also online tuts. Fucking amazing chemistry!
If you aspire to being a synthetic chemist, check out this site
InnoCentive
Apologies everyone, I know this isn't really drug discussion. Try to think of it as discussions on the fundamental principles of drugs, part of a complete HM education.
Enjoying your posts Jester.

Okay, consider this the possibly last post I'll be making on this thread...(and it's just to kiss phase_dancer's arse)
Thanks phase_dancer, as a matter of fact, I'm doing an "Applied Chemistry" and "Nanotechnology" degree somewhere in Sydney, and I've just finished my first organic chem course. It is my sneaking suspicion that they're really dumbing down these courses due to the fact that it's a 66 UAI to get into applied chem, thus I do a lot more reading on the chem things that interest me.
The mechanisms and topics all sound alien to me, so I guess I'm gonna have even more stuff to read about on my holidays.
If you have any more chem books that would help me, or URL's, drop us an email or something.
So yeah, thanks for all the info in all the posts phase_dancer. You're a gentleman and a scholar.
P.S Synthetic chemist is my second choice of career, right after doped up rockstar.

Reaction kinetics and the movement of electrons in different reaction types were probably the parts of 2nd Year Organic Chem that confused me the most. Somehow organic was always more interesting to me than inorganic chem, in terms of hands on value the inorganic pracs were about producing wonderfully coloured liquids, and the organic pracs about wonderful aromas hehehe. I think I got bogged down too much in the learning of the foundations though to be able to see the applications of the chemistry - which was why I stuck with physical chemistry, and then eventually just physics.
Chemistry is definitely one of the more fascinating but confusing topics to me though. It boggles my mind though, when I read the usual off-the-cuff statement about 'you'd need 2nd Year Organic chemistry experience to be able to synthesise MDMA from its precursors'... perhaps it's just too long since I was in 2nd year and I've forgotten a lot of stuff, but there's no way in Hell I'd be able to follow the recipes in PiHKAL or TiHKAL without a *lot* of reference books. Even if the precursors were available, I'd surely blow myself or the surrounding postcode up before I had a product that I'd feel confident putting into my body. I'll just continue being thankful that there are others who know what they're doing out there *lol*.
BigTrancer

Interesting thread for chemists (everybody else well it's just too jargon filled to make any sense). Now i remember why i dropped organic chem for pharmacology and behavioural neuroscience, although it is now apparent that i'm rather rusty and will have to ramble through Zumdahl and McMurray again (D'OH!)
P.S. Anybody that has trouble sleeping or is on the pills or meth should read McMurray it'll put you to sleep quicker than you can say Friedal-Craft reaction plus grignard reagent!