Sciencemadness Discussion Board

Replacement solvent for cyclohexane in demethylation of eugenol

organometallic - 8-9-2007 at 08:21

The procedure is as follows:

Aluminum Triiiodide preparation
1 mol Al turnings (or foil or powder all work well, powder is the quickest closely followed by foil then turnings a distant third) is combind with 1.5mol (note the excess of Al) of Iodine in 1000mL of cyclohexane (exchange solvent as needed but not diethyl ether!). This mix is stirred under reflux until the red colour has turned to a grey (about 1.5hrs with powder, 2-3 with foil, 4+ with turnngs). At this point the heat is turned off and the AlI3in solvent allowed to cool to room tempeature with stirring.

Reaction with Eugenol

In a dropping funnel, eugenol (1 mol), tetrabutylammonium iodide (1/360 mol) and a little cyclohexane are combined. This is slowly dripped into the AlI3/cyclohexane mixture made in the previous step with vigourous stirring and inert gas sheilding. After all the eugenol has been added the solution is brought to reflux (it is a tan coloured slurry at this point, but upon refluxing turns less viscous) for 1 hour. The solution is then cooled in an ice bath and hydrolysed with ~600mL of water, slowly.

The resultant mix is filtered under nitrogen and the solid collected immersed in ethyl acetate, this is swirled for a couple of minutes, then filtered. The ethyl acetate is seperated from the water (collected through the filtration) and removed and what you have left is a tan coloured solid with a charactistic 'smoke' smell and a melting point 45-51°C, althought this range could be tightened by recrystalisation or vac distillation with hot water in the condenser.

My question is: Would toluene be a suitable replacement solvent?

pantone159 - 8-9-2007 at 09:48

I don't know about the solvent change.

I am curious, why the phase transfer catalyst (Bu4NI) is needed when there is no water, and all the solvent is cyclohexane. I'm assuming eugenol is soluble in cyclohexane, so it seems like it would all be one phase, so why the PTC?

unionised - 8-9-2007 at 11:00

Would AlI3 catalyse the conversion of toluene to benzene, xylene etc?

JohnWW - 8-9-2007 at 11:24

So, you should look at benzene as an alternative hydrocarbon solvent. Another possibility could be mixed non-cyclic aliphatic hydrocarbons ("petroleum ether") of similar molecular weight to cyclohexane. Common gasoline, if there are no additives in it harmful to the reaction such as alcohol, and no toluene in it, or alternatively kerosine to reduce the fire hazard, may do.

[Edited on 9-9-07 by JohnWW]

organometallic - 8-9-2007 at 11:33

Hmm. That didn't occur to me..I have no clue what the PTC is used for, after all, eugenol is supposedly soluble in practically all organics. I can only assume it is not soluble in cyclohexane..=/ wait, shit, i think i just answered my own question..if anyone can confirm its soluble in toluene, that would be lovely though.
Anyway, do you reckon that a suitable substitute for Bu4NI would be a couple of blobs of hair conditioner? It contains a couple of different quaternary ammonium compounds.
The full link is here.

organometallic - 8-9-2007 at 12:08

Alright, thanks for the help guys, I will try it with unleaded petrol from the UK in a few days time, when I get the chemicals.

Sergei_Eisenstein - 8-9-2007 at 13:32

It is likely toluene will be a suitable replacement for cyclohexane. Be careful when preparing the AlI3. Better to try a small-scale preparation first. The reaction between Al (foil) and iodine can be vigorous, and decomposition of AlI3 with water gives HI. It's not the kind of reaction you want to experience a runaway with.
Quote:
I am curious, why the phase transfer catalyst (Bu4NI) is needed when there is no water, and all the solvent is cyclohexane. I'm assuming eugenol is soluble in cyclohexane, so it seems like it would all be one phase, so why the PTC?


In this case, Bu4NI is not used as a PTC but as a source of (highly) nucleophilic iodide.

organometallic - 8-9-2007 at 14:03

Quote:

In this case, Bu4NI is not used as a PTC but as a source of (highly) nucleophilic iodide.


I see..well, a tiny amount (1/360 moles) of it is cited in the ingredients list, so what part does it play in the reaction? Thanks for the help btw.

Sergei_Eisenstein - 8-9-2007 at 14:50

Several Lewis acids can be used to cleave alkyl aryl ethers: AlCl3, BBr3, AlI3, ... They all proceed via similar reaction mechanisms as well, viz. the Lewis acids forms a complex with the lone pairs of oxygen. This complex can be somewhat compared to an intermediary oxonium (Meerwein reagent):

PhO-Me + AlI3 ---> PhO-AlI2 + MeI

The resulting aluminium diiodide phenolate can be hydrolyzed at the end of the reaction, setting free the phenol. It is not strictly necessary to add iodide to the reaction mixture, but it has a positive effect on the reaction time (and possibly yield as well). The intermediary "oxonium" will decompose faster when iodide is available.

stoichiometric_steve - 9-9-2007 at 00:30

so you end up with an equimolar amount of Methyl Iodide, would probably be favourable not to attempt this reaction in a bedroom lab.

organometallic, if i'm right about what you're about to make as an end product, there are WAY cheaper and less toxic ways...which are, in fact, legal (unless you reduce the last reactive intermediate).

Nicodem - 9-9-2007 at 00:38

Quote:
Originally posted by unionised
Would AlI3 catalyse the conversion of toluene to benzene, xylene etc?

That is a good question that actually belongs to another thread dicussing benzene preparation. Until recently I believed Lewis acids would be able to catalyze the disproportionation of toluene to xylene, benzene, etc. Yet they do not, at least not by themselves. The presence of a protic acid is required for any Friedel-Crafts disproportionation. In some cases traces of moisture might suffice for certain substrates, but generally one needs the presence of HCl or HBr in addition of AlCl3 or AlBr3. The reason is in that FC disproportionation is based on the reversibility of the FC alkylation mechanism which means all the reaction components need to be present (HX otherwise forms during the alkylation of ArH with RX). Another reason why toluene can not disproportionate just like that is in that the disproportionations only work well with alkylbenzenes where the alkyl group can form stabile enough carbocation. The methyl group is not such and I would expect a terribly slow disproportionation even under optimal conditions. It does work with ethylbenzene though. For more information see:

Lien, A. P.; McCaulay, D. A. Disproportionation of Alkylbenzenes. I. Product Distribution and Rate Studies. J. Am. Chem. Soc., 75, 1953, 2407–2410. (and the rest of the papers from the series)
Brown, H. C.; Smoot, C. R. Disproportionation of the Alkylbenzenes under the Influence of Hydrogen Bromide and Aluminum Bromide; the Nature of the Transition State in Disproportionation Reactions. J. Am. Chem. Soc., 78, 1956, 2176–2181.
Baddeley, G.; Holt, G.; Voss, D. The isomerisation of p-xylene. J. Chem. Soc., 1952, 100–105.

organometallic - 9-9-2007 at 04:35

@steve:
Quote:
so you end up with an equimolar amount of Methyl Iodide, would probably be favourable not to attempt this reaction in a bedroom lab.

organometallic, if i'm right about what you're about to make as an end product, there are WAY cheaper and less toxic ways...which are, in fact, legal (unless you reduce the last reactive intermediate).


-Hm, you make a good point. My lab does happen to be in a confined space, but I have adequate air-extraction facilities.
-What are these cheaper and less toxic methods? This was the only one I found the chemicals for which I could acquire.
-You probably are right. To summarise: Eugenol---demethylation(preferable without poisoning self)-->dihydroxy intermediate ----methylenation--->you know what.
Yours, OM

[Edited on 9-9-2007 by organometallic]

unionised - 9-9-2007 at 08:29

I had forgotten about the requirement for HI to get the toluene to benzene etc reaction but the presence of methyl iodide from the intended reaction means I'd sooner use a straight hydrocarbon mix like pet. ether or kerosene.
I'd not try using unleaded petrol as it's got quite a hight concentration of toluene etc anyway.

stoichiometric_steve - 10-9-2007 at 03:30

Quote:
Originally posted by organometallic
@steve:
-You probably are right.


of course. i am king of being-right-land :P

you need to contact me via U2U, because i don't want to spill out valuable knowledge to the ones who don't need it. there are sources that could run dry quickly if one doesn't pay attention to whom he conveys certain methods.

i am actually against this kind of behaviour, since restriction of knowledge led to the society of energy slavery we currently live in, but there are situations when this very restriction is needed to preserve certain degress of freedom to the dedicated experimenter. how deliciously absurd!

microwave demeth procedure

v16 - 8-4-2008 at 17:43

may work for this application. But would probably attack the alkene, too.

EXAMPLE 5

In a 50 cc glass sealed tube, 0.8304 g of 2,7-dimethoxynaphthalene, 1.2 ml of 35% hydrochloric acid (equivalent of the methoxy groups) and 18 ml of acetic acid were placed. In an oven-type microwave irradiator where power and temperature are controllable, the mixture was continuously irradiated with microwaves having a frequency of 2.45 GHz and a power of 400 W, and then subjected to the reaction at 140° C. and 0.51 MPa for 2 minutes. The reaction mixture was analyzed using liquid chromatography, showing a yield of the objective compound (2,7-dihydroxynaphthalene) of 94.4% and a residual ratio of the starting material (2,7-dimethoxynaphthalene) of 0.0%.

The resultant mixture was subjected to the same process as in Example 1, obtaining an objective compound (2,7-dihydroxynaphthalene) having a purity of 99% at a yield of 93%.

http://www.freepatentsonline.com/6656328.html

organometallic - 8-5-2008 at 09:13

interesting, v16. It doesn't really matter if it attacks the alkene, because it would most likely add HCL accross the double bond markovnikoff-style, which could allow MDP2Pol to be produced, maybe.

Eugenol is a complete bitch

kalacrow - 23-5-2008 at 16:50

Eugenol is SO suceptible to side chain reactions, it polymerizes and freaks out if you look at it wrong. So if you are trying to get to Hydroxychavicol (4-allylcatechol) keep that in mind.

One researcher used BBr3 at -78C and did it just fine, but BBr3 is VERY nasty and not.. commonly available :)

Here is a procedure from 1934 describing cleaving with a simpler process. Note that they mention that the yield from using chloroform was 70%, and chloroform (bp. ~61) is very easy to prepare. It is also of note that the bp of chlorobenzene is 131, and nitrobenzene is ~211, so clearly you want the temp to be around 130 or so, at least in the case of THEIR olefin. Eugenol has different properties, so there will be some twiddling involved, especially since AlCl3 is a weak-ish lewis acid.. which is probably why temps needed to be so high to get good yields. But it is very easy to prepare, so yield loss might not matter.

I haven't tried this with Eugenol yet, but I will probably give it w whirl at some point soon.

Hydroxychavicol, by the way, is a very potent anti oxidant, used to keep fats from going rancid. It is also unstable in moist air, and (purportedly...but better safe than sorry) to light, so if you do succeed, dry it right away and bottle it up in brown glass, wrapped in black plastic.
====

Imoto and Ono, Journal of the Chemical Society of Japan, vol 55, pg 275-9 (1934) (Chemical Abstracts 4048' vol 28) report on cleaving methylene ethers of several compounds by refluxing the compound with AlCl3 in chlorobenzene as solvent. This method should be perfectly applicable to cleaving eugenol's methyl ether (experiment is king). Yields were as high 96% (for piperonylic acid) with chlorobenzene as solvent. 1,2-dicloroethane as solvent gave yields of 90% for demethylenation of piperonylic acid, chloroform 70%, and nitrobenzene 3%. Generally the chemist would reflux (with stirring) 164g dried eugenol (1 mole) in 1000g of chlorobenzene and add in several portions AlCl3 (totaling 500g) over 2.5 hours in a reflux apparatus fitted with a calcium chloride tube. After refluxing add dilute hydrochloric acid (15-20%) to the warm solution with stirring until the mixture is definitely acidic to congo red indicator. Extract the aqueous layer with several portions of ether. Extract the ether with portions of dilute 5% sodium hydroxide solution. Acidify the aqueous solution and extract with ether. Separate the layers and distill off the ether and collect the product. The original article will have to be consulted for their exact method and purification scheme.

[Edited on 23-5-2008 by kalacrow]