ning (Newbee)
10-01-03 04:08
No 461979
       High yielding methylation of 2,5-dimethoxytoluene     

Another find... let me know if this is already known...
While searching for info re DOM, I discovered a way of methylating 2,5-dimethoxytoluene thats pretty OTC: read this:



Syntheses. (a) 2,5-Dimethoxymethylbenzene
In a dry three-neck 1-L RB flask equipped with a magnetic stirring bar, two stoppers, a reflux condenser, and an Nsub]2[/sub] inlet was placed 2,5-dihydroxymethylbenzene (49.6 g, 0.40 mol). To the flask was added 300 mL of ethanol and the solution was slightly heated with a mantle until the solid dissolved. The heating mantle was then removed, and the solution allowed to cool to room temperature. Over a period of 20 min, DMSO and 100 mL of an aqueous NaOH solution (~10 M) were added to the reaction mixture. The heat released  was sufficient to bring the solution to boil. After this step was completed, NaOH (10 g, 0.25 mol) in 10 mL water was added to the solution to make it alkaline. When the boiling subsided, the heating mantle was replaced and the reaction mixture refluxed for 7 h. The reaction mixture was checked by TLC and then transferred to a separatory funnel. The organic fraction was extracted with ether and washed with saturated NaCl solution. The resulting solution was dried with MgSO4, filtered, and then concentrated on a Rotovap. The product was then subjected to flash chromatography. (20% ether, 80% hexane), yielding a light yellow liquid: yield 53.3 g (93.9%)



I read that DMSO, when heated to reflux, disproportionates to dimethyl sulphite, etc, which is a methylating agent. So I wonder, could this method be more generally applicable? Seems like a wondercure to me. Anyone know how this reaction works?

Oh, the ref: Analytical Chemistry, Vol 67, No. 24, Dec. 15, 1995 		 
 
 
 
    hypo
(Hive Addict)
10-01-03 09:48
No 462037
       it's a typo     

Post 460607 (psyloxy: "DMS  methylation of toluhydroquinone in 90%+ yield", Chemistry Discourse)

in dimethyl sulfite, the CH3- is connected to a less electronegative
atom (S), so it is hardly an alkylating agent. (i believe)
n'importe quoi 		 
 
 
 
    Vitus_Verdegast
(Hive Bee)
10-01-03 16:07
No 462079
       dimethyl sulfite     

Dimethyl sulfite can be used as a methylating agent, although yields are not good. I've seen patents where vanillin amongst others is methylated by dimethyl sulfite.

Post 330859 (Antoncho: "Dimethylsulfite.", Chemistry Discourse)
A Dream Within A Dream (http://www.poedecoder.com/Qrisse/works/dreamw.html) 		 
 
 
 
    hypo
(Hive Addict)
10-01-03 17:19
No 462089
       oh, yeah...     

you're right. i confused this with dimethylsulfide ((CH3)2S).
in the sulfite, the CH3- is connected an oxygen, so
at least my theory isn't totally off wink.
n'importe quoi 		 
 
 
 
    ning
(Newbee)
10-01-03 19:46
No 462102
       if it works...     

it would be amazing. DMSO seems alot more accessible than Dimethyl sulphate. Who wants to try? 		 
 
 
 
    psyloxy
(Hive Addict)
10-02-03 09:24
No 462247
       no need to try :( - it really is a typo     

There really is no reason to believe this reaction could ever happen as written down in that paper. DMSO has a totally different reaction profile. If they would have been able to do it like the say (probably not even being aware of it, cause it is a typo) that would be a revolutionary success and they would have announced it in a different way then silently putting the synth amongst many others, like it's a standard procedure. On the other hand, if you take into consideration the possibility of a typo, it all makes sense. DMS instead of DMSO, dimethylsulfate instead of dimethylsulfoxide, a well known standart-methylating agent instead of a solvent that can react with aromatics in many bizarre ways but never ever donates a methyl group to a phenolic or any other HO- group. It is not too uncommon to find errors like that even in the scientific literature/Beilstein. I've encountered a hand full over the few weeks I use it. My favourite beeing piperonal from meta-methoxybenzylacohol. If anyone wants to try it:

Reference:

Krohn, Karsten; Khanbabaee, Karamali; Rieger, Hagen; CHBEAM; Chem.Ber.; EN; 123; 6; 1990; 1357-1364.

Abstract:

Primary and secondary benzyl alcohols are selectively converted in high yields into the corresponding aldehydes or ketones using tert-butyl hydroperoxides and catalytic amounts of titanium or (better) zirconium alcoholates.Aliphatic hydroxy groups, double bonds (except those in allylic position to hydroxy groups), and phenolic hydroxy groups (except those in the ortho position to the benzylic alcohol) are not attacked.

You see they don't talk about any magical rearrangement here... but hey, maybe someone should prove me wrong, I'd be most happy with that :)

--psyloxy--