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 70.degree. 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 84.degree.-85.degree. 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
![Smiley :)](https://thevespiary.org/talk/Smileys/default/smiley.gif)
, 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!
Yours,
Antoncho