Author Topic: An interesting chloromethylation procedure  (Read 724 times)

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  • Guest
An interesting chloromethylation procedure
« on: June 14, 2002, 07:41:00 PM »
Oh my dear friends!

Look what i recently found while researching the subject of chloromethylation in the patent databases, in

Patent US4267382


68.0 g. of 2-methoxy-4,6-dichloro-toluene are mixed with 235 ml. of acetic acid, 446 ml. of hydrochloric acid (37% w/vol.) and 107 ml. of formaldehyde (35%). The resulting mixture is stirred at C. for 3 hours and, after cooling, introduced into 200 ml. of water. The aqueous solution is extracted three times with 1000 ml. of methylene chloride.

The methylene chloride extract is washed three times with 1000 ml. of water, dried over sodium sulphate and evaporated. The residual 2,6-dichloro-4-methoxy-5-methyl-benzyl chloride is purified by adsorption on silica gel using low boiling petroleum ether for the elution. After recrystallization from hexane, the resulting 2,6-dichloro-4-methoxy-5-methyl-benzyl chloride melts at C.

No mention of the yield, but in the consequent synthesis they use 52g of that Bz-chloride - maybee that's what they got - the other yields are also unspecified, but the weights seem to bee consistent.

Now, you of course noticed that this rxn is quite curious for three independent reasons:

1) The ring is quite deactivated, but chloromethylation seems to proceed well.
Of course :) , the thing that i have in mind is 2-bromo-diMeObenzene, which is also deactivated and requires much harder (as compared to tolu- or alkylthio- diMeObenzenes) conditions - as submitted by Karel in

Post 299551

(karel: "Chloromethylation", Chemistry Discourse)
. There one can see that the rxn is run unhydrous and w/help of PTC - at an elevated temp.

2) But the really awesome detail is that here there's no mention of bubbling HCl!

Needless to say, at 70-80 C the outgoing stream of gas will carry much of bis-dichloromethyl ether, which boils at 101C and is VERY carcinogenic. Not that at lower temps the 'classical' procedure wasn't nasty enough, but to do that at 80C would definitely require a lil more that a kitchen w/a self-made glovebox :)

IF this procedure can bee applied to our haloDMB, we'd get a way of performing all this in a closed vessel - i.e., even w/out even real need for a fumehood!

3) Did you notice that AcOH is applied as an acid catalyst (while usually ZnCl2 or some such are employed)?

Maybee precisely THAT is the trick that allows one to use aq. HCl, even for electron-poor rings?

Anyway, guys, please tell me what you think, i really wish there will bee some input on this particular issue! :)




  • Guest
does this mean..
« Reply #1 on: June 17, 2002, 04:24:00 AM »
that one could substitute the molar amount of benzene, and just replace the formaldehyde solution with a molar amount of paraformaldehyde?

But if it performs this well on deactivated rings, will it stop at the first chloromethylation? :(

Do not go gentle into that good night.  Rage, Rage, against the dying of the light.  --Dylan Thomas


  • Guest
Good point!
« Reply #2 on: June 17, 2002, 02:08:00 PM »
.... i however don't think that double Clmethylation would occur.

-CH2Cl group is pretty deactivating by intself.

Beesides, you can always use an equimolar amt. of HCHO.

Well, i think maybee you could try it and tell us what happened - i myself would dearly like to hear some research on this - unfortunately, after G_Pig noone ever looked into these pathways.

I'm planning to do some research myself but i have very little time and several other projects at hand :)



  • Guest
I think if this works well, and in high yeilds, ...
« Reply #3 on: June 17, 2002, 08:04:00 PM »
I think if this works well, and in high yeilds, it can be, like you said, an awesome procedure.  You wouldn't necissarily even need a reflux condensor, you could just pop a stopper in the flask!  This looks VERY easy, I'll have to try this one out.

Do not go gentle into that good night.  Rage, Rage, against the dying of the light.  --Dylan Thomas