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pip
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I don't understand by what you mean by chain homologation extending the chain on thc? I'm really not after thc so discussing how to take it and
extend/shorten the chain to make an analog isn't an subject I am trying to touch on.
Just so I don't get flamed I am talking about an ethyl or n-propyl resorcinol while olivetol is n-amyl and supposed to be the shortest chain possible
for an thc analog to have activity.
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Arrhenius
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I'm not trying to flame you, but having thought about THC analogues a bit myself, I figured that's probably why you're interested in olivetol &
friends. Anyhow, like I said, resorcinol is unfortunately not a good starting point for these materials. Realistically, you would want to start with
something like m-dinitrobenzene or m-dichlorobenzene, which will give you the correct electronic effects to get the alkyl group in the correct
position. Still, by this route I think you'll find the Friedel-Crafts reaction a substantial hurdle.
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pip
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I just found this and it's for what i want but not thc however the patent imply's that increasing pressure to favor alkylation instead of dealkylation
would help solve the problems of using the longer chain alcohol's
Attachment: Process_for_producing_mono_substituted_Resorcinol.pdf (134kB)
This file has been downloaded 1914 times
since I answered my own question I apologize for taking the thread off topic.
[Edited on 3-6-2009 by pip]
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Arrhenius
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Doesn't sound too promising as a laboratory prep reaction. Vapor phase 350-415C to get a mixture of 2, 4 and 5-Me/Et/Pr resorcinols. Yikes.
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pip
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Um you don't add all three alcohol's only the one you want to react. It can be methanol ethanol or propanol and the vacuum distillation/ fractional
crystalation purifies it. And the min reaction temp is 276c not 350 to 400
Building an reaction vessle from scratch is less daunting than all the protection/deprotection involved with the classic ways not the mention all the
conversions to get the product. Isn't the classic olivetol synth. like 7 or 8 steps?
Besides what's really needed as an reaction vessle why can't an glass vessle be filled with the right amount of reaction mixture so when the vessle is
evacuated and sealed all the mixture can be heated to vapor phase while creating only enough pressure to satisfy patent requirements? I understand
that might limit scale but hey it wouldn't take longer overall than the other ways.
[Edited on 3-6-2009 by pip]
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BabyBird
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apologies if this is taking this thread further off topic,
you are going to struggle to get friedel-crafts on a phenol to give a meta substituted product. it just won't do it, unless you are willing to make
ortho para and then rearrange with HF at high temps to the more thermodynamically stable meta substituted material.
friedel crafts alkylation of phenols using alcohols or alkenes and a strong acid gives primarily mono alkylated material, indeed this is the
commercial way of making nonyl phenols and a raft of other alkyl phenols. para can be selected for over ortho using zeolites.
O-alkylation is not usually a problem because under the influence of strong acid the O alkylated material will re-arrange to the c-alkylated material.
so if you have a way to meta alkylate a benzene ring with a very strong activating ortho para directing group such as phenol you are much cleverer
than me.
similarly if you can F-C alkylate a benzene ring with meta directing groups like nitro or similar or worse 2 meta directing groups in anything like
decent yield you are again much cleverer than me. it is going to require high temps and tough conditions if it works at all, but at high temps the
alkyl cation is going to rearrange to the more stable secondary or tertiary cation, giving branched chain f-c products.
from memory the large scale olivetol syntheses used in the past used dihydro resorcinol monoethyl ether and a suitable alkyl organometallic adding 1 4
and then aromatize the product to the olivetol or meta subd phenol. this only works with straight alkyls.
[Edited on 5-6-2009 by BabyBird]
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pip
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The patent isn't an freidels-craft reaction as there is no halide and I might be wrong but I don't think titanium dioxide is an lewis acid . Babybird
do you see a reason why the patent maybe bunk? Also mods maybe this should be split into an new thread?
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Nicodem
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Reactions do not get classified due to the reagents used, but due to the mechanism of the reaction. Thus a Friedel-Crafts alkylation needs not to
involve alkyl halides (see http://en.wikipedia.org/wiki/Friedel-Crafts_reaction for examples or other precursors to the reaction electrophile). In fact, I think the most
common reagents used in industry to form the electrophiles for the FC alkylation are alkenes rather than alkyl halides. If the reaction involves an
alkylation at the aromatic ring and the carbocentered electrophile is created by acid catalysis (either from an alcohol, alkene, alkyl halide,
ketone/aldehyde, or other) the reaction is a Friedel-Crafts alkylation, because unless a different mechanism is proven, an electrophilic aromatic
substitution mechanism is assumed. Titanium dioxide, at least some of its forms, is an acid, though not TiO2 itself, but its surface is acidic.
Similarly like silica, some forms of alumina and some zeolites.
BabyBird is right about the limitations in using FC reactions to obtain the thermodinamic product. In FC alkylations it is generally very difficult to
obtain the thermodynamic product (=the product at which the rate of the retro-Friedel-Crafts reaction is the slowest). With alkyls such as t-butyl,
benzyl and related this is not so difficult and can be done at "normal" temperatures with "normal" acids, but with less transferable alkyls (like the
methyl or ethyl) the conditions needed can be really extreme. The method of the US4086281 patent posted above is most unlikely to be of any use for
the synthesis of olivetol, or even 5-propylresorcinol, because you can not introduce n-alkyl groups via a Friedel-Crafts reaction.
1,2-Hydride shifts in carbocations are considerably faster than the rate of FC reactions, thus that patent method should give 5-isopropylresorcinol
regardless if you use isopropanol or n-propanol.
Besides, alpha-resorcylic acid is commercially available and very cheap. I'm quite confident its reaction with excess n-BuLi in THF would
give 1-(3,5-dihydroxyphenyl)pentan-1-one (at least three equivalents of BuLi are needed since two are lost at the phenolic groups).
1-(3,5-Dihydroxyphenyl)pentan-1-one can be reduced to olivetol by various means (hydrogenation over Pd-C would be the simplest method, or else
reduction with silanes, but Clemenssen or Wolff-Kishner reductions could work as well). Since alpha-resorcylic acid, BuLi and Pd-C are all
commercially available and relatively cheap, this might be the cheapest two step synthesis of olivetol possible. Of course, to see how possible this
is one should first check the literature, but I leave that to those who are interested and not too lazy.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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pip
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Again olivetol is not the goal so the patent will work fine for the ethyl group I want. Thank you Nicodem I found that very informative, I had
forgotten that it is more than just the halides that classify as an F/C reaction.
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-TheMadMen-
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| Quote: | -TheMadMen-: Friedel-Crafts reaction is really not that glorious. The 'atom economy' of the reaction is pretty awful considering it takes a mole
equivalent of Lewis acid. Palladium chemistry is probably a better option.
I presume the desire to make allyl benzene is to access a renowned illicit substance. In that regard 1-phenyl-2-propene is a more easily had product.
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No no, i do not engage in the chemistry that i was recommending for this particular post. However, I believe allylbenzene is actually an illicit
precursor in itself yes?? In so being, it is illegal to possess without a license, in which case, 1-phenyl-2-propene, or allylbenzene, is irrelevant
really. But as to the atom economy aspect, you are correct indeed, it is a very inefficient reaction from a statistical point of view, but it's not as
if the benzene is destroyed, it just remains unreacted, so it can be fed back into the process over and over again. So from an economical aspect, it
is seemingly superior.
In any case however, making either will likely lead you into some serious trouble with the law!!! :-)
[Edited on 11-6-2009 by -TheMadMen-]
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Arrhenius
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Sure, but you can't recover the Lewis acid catalyst  So if you use ferric
chloride, you will use more lewis acid (on a molar basis) than yield product.
Law... eh.... I got a ticket for riding my bicycle on the sidewalk the other day. I could care less about the law.
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-TheMadMen-
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Ha ha, i like your attitude towards the law. Same same, straight from my heart. Heh. But i don't like jail that much......  So sometimes the law has to take first place.
And what you just said about the Lewis acid catalyst does indeed make sense, i forgot all about that, that's a bloody piss-off that is. Feeding the
aluminum chloride into the reaction over and over again, never to see it again. It's a pity that aluminum chloride was not more available. I Am not
that adept at my understanding of Lewis acid catalysts, but i would assume that aluminum chloride is both the cheapest and most economical of them
all? From a practical standpoint. For friedel-crafts, at least for the home chemist?
I Don't want to veer off course, which i am, i am sure that there is a thread already for it, but i am going to say it right here, as far as preparing
aluminum chloride goes, does the hydrochloric acid product, or the hydrolyzed form, work in friedel crafts? Or is it only the anhydrous form that
works? Which is made by passing chlorine gas through molten aluminum? Hmm..... Food for thought hehe.....
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Paddywhacker
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Anhydrous only... same as FeCl3
But the Al does not need to be molten. You could pass dry Cl2 into Al powder in dichloromethane. Or use bromine or iodine instead of chlorine...
that might be easier.
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-TheMadMen-
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Thanks for the advice Paddywhacker, i appreciate it. Is it possible to use any other solvent other than dichloromethane however? As funnily enough
that is one thing i just don't have sitting around, either way, it beats having to make a furnace to contain molten Al anyday.
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Arrhenius
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It really makes more sense to buy it. FeCl3 is weaker than AlCl3, but will still work in most cases for friedel-crafts alkylation. FeCl3 is cheap,
and I don't think you should worry about buying it. People are awfully paranoid here, but I think the headache gained by trying to make either of
these lewis acids in an anhydrous fashion is worse. You cannot heat either of these to drive off water. Their hydrates are available everywhere, and
are pretty useless unless you make metal art 
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Paddywhacker
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If you are doing FC on a micro scale then it should be possible to prepare the catalyst in whatever solvent you are using for the FC from the metal
powder and halogen, but really, as the previous poster said, anhydrous FeCl3 and anhydrous AlCl3 are not difficult to purchase.
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Nicodem
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You can not use AlCl3 for Friedel-Crafts allylation of benzene and certainly not with allyl chloride or bromide since allylbenzene reacts further with
HCl/HBr to give a complex mixture of further alkylation products. It is done using ZnCl2 (or other suitable acids) and allyl alcohol. Check the
literature.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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-TheMadMen-
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Where would one find Anhydrous AlCl3 to purchase? Chem supply store? Hardware store???
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Arrhenius
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Definitely not the hardware store, haha. A well stocked chemical supplier.
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-TheMadMen-
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Ohh, ahh i see:-) Hehe, i just remember some kind of chloride being sold at hardware stores, for welding or something, must have been ammonium
chloride i guess......
I'll have to find a chemical supplier who can stock me up, ain't that easy to find many of ' em around here who will take on orders from the public.
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pip
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nicodem does the n-BuLi have to be in thf because in hexanes are more available not that I plan on doing it but an anagulous one with n-propylLi
maybe.
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Helgoland
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Two things
1.Complete hydrogenation of cinnamaldehyde (from cinnamon oil) using a catalyst and elimination of remaining alcohol group
2. If one were interested - purely theoretical, of course, we're all law-abiding citizens, aren't we? - in amphetamines: Friedel-Crafts using acrylic
acid chloride, addition of HCl (not BrCl) and Clemmensen reduction
I don't have any practical experience, so please tell me if this is total crap; but I hope this would work.
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entropy51
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Total Crap
Why are you asking about amphetamines in a thread on allybenzene?
Did you get lost on the way to Wet Drums or the Heave?
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bbartlog
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He also asked about HCN in the methylamine thread. Seems to not have any idea that threads might actually be, you know, for the specified topic. And I
thought I was a noob.
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Helgoland
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@entropy51: Because amphetamine might be synthesised from allylbenzene (I guess). If mentioning this was inappropriate, I apologise and would edit it
if the edit button for that post hadn't disappeared.
@bbartlog: I thought it might be used in methylamine synthesis. If that's total crap, I apologise again. I know I'm a noob, so tell me when I get
something wrong. But please read what I write first.
In order to (try to) contribute: What reduction method can be used for reducing both aldehydes and alkenes?
[Edited on 8-1-2010 by Helgoland]
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