sparkgap
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Attaching polyene allyl groups to benzene derivatives
Are there any methods to attach a possible polyene alkyl group to a benzene ring? Apparently Friedel-Crafts will give a mess.
sparky (~_~)
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UnintentionalChaos
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Quote: Originally posted by sparkgap  | Are there any methods to attach a possible polyene alkyl group to a benzene ring? Apparently Friedel-Crafts will give a mess.
sparky (~_~) |
How many-ene? Two or three? or short polymer chain? At any rate, I'd start with a phenylacetylene if that gives a usable starting spot.
trimethylsilylacetylene is probably going to be very useful if you can make it.
[Edited on 3-24-09 by UnintentionalChaos]
[Edited on 3-24-09 by UnintentionalChaos]
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sparkgap
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Well, the simplest cases of interest for me would be geranylbenzene and linalylbenzene. I have geraniol and linalool at hand so it's what I wish to try first before moving to more complicated polyenes. I'm really quite
sure I'm missing something obvious, but having to filter through loads of searches for days on end can do that to you... 
sparky (~_~)
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Nicodem
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Geranylbenzene can probably be made by simple alkylation of phenyl lithium or phenyl magnesium halide (both commercially available) with a geranyl
halide or tosylate. This would not work for linalyl however, but chances are you might get good yields of linalylbenzene by simply refluxing linalool
in benzene with an amberlist-type solid acid catalyst (the carbocation that forms from OH protonation is also the most stabilized possible in that
substrate and the use of a solid catalyst might inhibit further reactions of the product).
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sparkgap
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Thanks Nicodem! Amberlyst does look attractive, good call.  Sadly, linalool is
the only tertiary allylic alcohol among the alcohols I'm looking at; apparently I'll have to do something similar to the one you proposed for
geranylbenzene for the other alcohols (the rest are all primary allylic polyene alcohols). I now figure I have to do a metallation for the other
substituted benzenes (and maybe protecting groups as well).
Speaking of which, there really are no other ways to tether alkyl groups to an aromatic center apart from Friedel-Crafts and metallation, are there?
sparky (~_~)
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not_important
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| Quote: Originally posted by sparkgap |
Speaking of which, there really are no other ways to tether alkyl groups to an aromatic center apart from Friedel-Crafts and metallation, are there?
|
http://en.wikipedia.org/wiki/Coupling_reaction
in particular for your case the Heck coupling.
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Nicodem
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Sparkgap, I'm afraid I misundestood that you want plain benzene derivatives. Unfortunately the example using amberlist would only be useful where the
aromatic substrate could be used as solvent, which is not the case when using more complex substrates. You might want to check Journal of Organic
Chemistry, 49 (1984) 4309-4310 and the references therein.
The alkylation of aryl lithiums works fine with primary allyl halides where the arylation would occur on a terminal C-atom, but the regioselectivity
is gone once you have an internal or secondary allyl halide, not to mention that elimination is the most likely outcome.
The Heck coupling would give styrenes, while I understood that you need allyl aromatic products? In such case the Kumada coupling between allyl
grignards and ArX might be useful (the newest catalysts allow for the reversed roles without troubles with the alpha-hydride elimination), Negishi
coupling can be done with allyl acetates, similarly with the Suzuki coupling. However, in any case, with couplings there is a lot of work involved due
to the need to prepare the corresponding organometalics. Yet in some cases they might be your only chance since it appears some of these couplings
using allyl esters preferentially give products arylated at the tertiary carbon, therefore having the regioselectivity opposite to that of allylation
of aryl magnesium or aryl lithium. You should check some review papers about it.
Also, if perhaps your targets are phenols or phenol ethers with the ortho allyl substitutent, the Claisen rearrangement might be another option to
obtain some of these products.
[Edited on 25/3/2009 by Nicodem]
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sparkgap
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Thanks n_i and Nicodem.
Nicodem, I did need geranylbenzene and linalylbenzene, but I was also going to go for joining polyene alkyl groups to a few other substituted
benzenes. I can at least protect aldehydes as glycol acetals and carboxylic acids as 4,4-dimethyloxazoline derivatives (subsequently turning those
carboxylic acids to esters after deprotection), so I'm still sure that I can give metallation a whirl. Heck would indeed not be appropriate because it
gives vinylic products and not allylic ones.
Thing is, I *really* wanted to avoid anything that will have to use palladium (I did remember those funky Japanese coupling reactions hours after
posting that last question, though) because it's a bit beyond my and "their" budget.  I guess I'll have to wing it...
Yes, I was also going to try making o-geranylphenol, but as I understood Claisen's rearrangement, there is a "flipping" that goes along, so if I
attempted it with geranyl phenyl ether, I'd get o-linalylphenol (but I do need it anyway).
sparky (~_~)
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not_important
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Palladium is not that expensive and recovery is generally good. Some of the ligands used will cost more than the Pd, which is why I try to keep up to
date on variations using cheap+common ligands or even none at all. Also you'll find that some variants get away with very low levels of Pd, under 1%
and even as low as 0,1 ppt.
[Edited on 26-3-2009 by not_important]
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Nicodem
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This thread is a split-off from "The short questions thread". At the request of Sparkgap in order to continue with the topic discussion.
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Nicodem
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Thread Moved
26-3-2009 at 06:14 |
chemrox
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rhodium re-print
Theres a Rhodium archive procedure allegedly copied from, [1] H E Carter, J Biol Chem 108, 619 (1935) that goes like this:
ph-mg-br-ether is reacted with allyl br after removal of all unreacted Mg. Allylbenzene is collected by distillation. I was thinking a coupling of
this kind should be catalyzed with FeCl3 but I didn't see that in the article. If anyone here knows more about this synthesis I'd appreciate hearing.
Nicodem?
http://www.erowid.org/archive/rhodium/chemistry/phenyl-2-bro...
I edited to add the J Biol Chem article:
http://www.jbc.org/cgi/reprint/108/3/619
I think this will load without a login if not I will post the article.
[Edited on 27-3-2009 by chemrox]
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Nicodem
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| Quote: Originally posted by chemrox | | I was thinking a coupling of this kind should be catalyzed with FeCl3 but I didn't see that in the article. If anyone here knows more about this
synthesis I'd appreciate hearing. Nicodem? |
What role is FeCl3 supposed to have? The reaction of Grignard reagents with benzyl and allyl halides is a common reaction, it goes rapidly and need no
catalysis. There are plenty of references for it. Maybe you confused this reaction with the Kumada coupling which does require a catalyst? But the
Kumada coupling is for aryl or alkyl halides with aryl or alkyl Grignards - something quite different, since these combination usually do not react
unless a viable organometalic mechanism is provided by a Pd, Ni or Fe catalyst.
…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)
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chemrox
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"Maybe you confused this reaction with the Kumada coupling which does require a catalyst? But the Kumada coupling is for aryl or alkyl halides with
aryl or alkyl Grignards "
Yes, that was what I was thinking. Thanks.
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sparkgap
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Along these lines, I came across this. It looks like something I have to try out (the alkylation, that is, not the polymerization), but the only thing bothering me is that I can't
come up with a plausible mechanism...anybody here have thoughts?
sparky (~_~)
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Nicodem
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I would be a bit sceptical about this paper. Check the 1H NMR of that compound that what they call "MGP". There is a mistake that might not really be
a mistake. They assigned the doublet at 4.42 ppm to a O-CH2- group which is not part of the MGP, but would be if the alkylation would give the
expected O-alkylation product instead of the unusual C-alkylation that they claim. Coincidently, aryl allyl ethers do indeed have the O-CH2 group
signal at about 4.5 ppm. Yet, the signal of Ar-CH2- of allylbenzenes is much lower, at 3.4 ppm (in CDCl3 at least, but should not be much different in
CCl4). Also note the absence of the phenolic singlet. These are sometimes wide and can be hard to spot, but still this is highly unusual, particularly
if one also notice that they gave the integral of the multiplet of the aromatic hydrogens the value of 4H! It seems to me they assigned the 1H
spectrum having the O-alkylation product while they claim the C-alkylation product in the scheme. I mean, these guys are polymer chemists, not organic
synthetics...
[Edited on 2/4/2009 by Nicodem]
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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
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sparkgap
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Hmm, you could be right that it's too good to be true... I suck at making sense of spectral information.
Here's one of the previous papers of their group where it is said that they were able to make 2,6-bis(3-methyl-2-butenyl)phenol. What do you make of
it?
(Too bad I can't seem to get the papers in the Kagaku journals...)
sparky (~_~)
Attachment: isop-VII.pdf (107kB)
This file has been downloaded 650 times
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not_important
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hmmm ... 0,05 moles of reactants, 0,21 mole of sodium, and they call the sodium a catalyst
| Quote: |
A substance, usually used in small amounts relative to the reactants, that modifies and increases the rate of a reaction without being consumed in the
process.
Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. |
Obviously all the phenolic HO- will be converted to the salt to start with. Possibly it could go to a quinoid form that is the actual reactant.
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Nicodem
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Yes, it is weird they use sodium (in such excess) instead of NaH and diethyl ether instead of THF. One would expect that they would explain the choice
of these conditions and relate them to the high C-alkylation selectivity. Yet they do not even bother providing any hypothesis or explanation for the
ortho- and C-alkylation selectivity observed. I think it is possible that prenyl halides do give such a large amount of C-alkylation by default, after
all even allylation of phenol with allyl bromide give some C-allylation product regardless of the conditions. The choice of the sodium phenoxide and
nonpolar solvent might aid this selectivity by sodium blocking the O-alkylation by chelation (the sodium ion is relatively acidic in nonpolar
solvents). But then why not presenting the observations as such instead of writing such shallow papers? In such case it could have happened to them
that they simply made a mistake and wrote down the 1H NMR data for the wrong compound (the O-alkylation side product) and that their claims are true.
Seems like you will have to try and see. Meanwhile, you might read the JOC paper they refer to and might shed some light onto this problem. Here the
authors used the Friedel-Crafts reactions with BF3 as catalyst in order to obtain the C-prenylated phenols, but they do discuss the prenylation of
phenols in basic media as well (and it seems their data supports the results of these later Japonese researchers):
Synthesis of 2-multiprenylphenols and 2-multiprenyl-6-methoxyphenols, biosynthetic precursors of the ubiquinones
G. Doyle Daves Jr., Harold Wesley Moore, Donald E. Schwab, Richard K. Olsen, Joseph J. Wilczynski, Karl Folkers
J. Org. Chem., 32 (1967), pp 1414–1417. DOI: 10.1021/jo01280a027
Attachment: Synthesis of 2-multiprenylphenols and 2-multiprenyl-6-methoxyphenols.pdf (575kB)
This file has been downloaded 574 times
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Ebao-lu
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Al(OPh)3 is another o-selective catalyst for alkylation of phenols with alkenes that can form a tertiary carbocathion (prob. tertiary alcohols also,
but i dont remember). This is a bit different from what you want, because you will get a fully substituted benzylic position. But maybe there can be
some applications of this method for 1,3-dienes or allyl alcohols(they both can form stable carbocathions not worse then substituted alkenes)? I guess
no.. because then the bees should have found this paper and posted on rhodium as a possible route for 1,4-dihydroxyallylbenzene..
The mech of Al(OPh)3 catalysis is the formation of
[Al(OPh)4]H which is a weak acid that protonates double bond of alkene, and carbocathion attacks o-position.
Al(OPh4) can be probably done from any unhydrous Al salt (the reaction obligatory requires unhydrous conditions)
[Edited on 4-4-2009 by Ebao-lu]
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Nicodem
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| Quote: Originally posted by Ebao-lu | | This is a bit different from what you want, because you will get a fully substituted benzylic position. But maybe there can be some applications of
this method for 1,3-dienes or allyl alcohols(they both can form stable carbocathions not worse then substituted alkenes)? I guess no.. because then
the bees should have found this paper and posted on rhodium as a possible route for 1,4-dihydroxyallylbenzene.. |
There are plenty of references for the allylation of benzene and alkylbenzenes with allyl alcohol (using ZnCl2 or other mild acids) or with allyl
chloride (with mild Lewis acids or ZnCl2 buffered with K2CO3 both on separate solid supports; with stronger Lewis acids one immediately gets further
addition of HX on the allyl group followed by numerous side reactions while with protic acids like H2SO4 the main products are ArCH(CH2X)Me type of
products). The only problem is in that this type of crude Friedel-Crafts alkylation is not apropriate for Sparkgap since they are only aplicable to
(alkyl)benzenes which are also used as solvents in large excess and to simple allyl alcohols/halides (but not really to polyene allyl
alcohols/halides). Yet, for the reactive phenols, the paper I attached above seems to indicate finer Lewis acids like BF3 (that do not have such
problems with decomposing in the presence of phenolic OH, as opposed to AlCl3), can be efficiently used even with such delicate polyene allyl
alcohols. I do not know if this would work also for nonphenolic aromatics (seems unlikely), but it looks like Sparkgap does not mind using phenols.
…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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sparkgap
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Well, I do need to make allylated phenols, but it also does look like I'll have to take up n_i's suggestion to do those couplings for the case of
non-phenolic derivatives. Unless you guys have other suggestions?
@Ebao-lu: Wouldn't just using an excess of hydroquinone with respect to allyl halide before doing a Claisen suffice? Still, as I mentioned upthread, my use of Claisen seems to be limited to flipping
geranyl to linalyl for phenols.
| Quote: | | [this type of crude Friedel-Crafts alkylation] are only applicable to (alkyl)benzenes which are also used as solvents in large excess and to simple
allyl alcohols/halides (but not really to polyene allyl alcohols/halides). |
Yeah, not a problem for me to use an excess of geraniol and linalool, but I don't think I can carry over that kind of strategy when I start using
farnesol and phytol (have you seen their listed prices on Sigma-Aldrich?!).
Also, as I had implied in my very first post, a good lot of the Lewis acids used for Friedel-Crafts would seem to have the benzene derivative react
with any one of the many double bonds as well as with the alcohol of halide functionality; i.e. a mix or a polymeric mess.
sparky (~_~)
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Ebao-lu
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Sorry, i wrote about Al(OPh)3 because did not understand what exactly was the aim of sparkgap. BF3 should be the best catalyst then.
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