11-23-00 20:04
No 70528
When I used the search engine to find prep of this compnd, on excellent Rhodium's
page I found Vilsmeyer formylation with only 40% yield. I decided to try more recent
modification of this reaction and here is the result...
The Vilsmeyer complex was prepared by 30 min addition of 92 ml phosphoryl chloride
(freshly opened ampoule) to 150 ml anhydrous DMF with stirring and cooling in ice.
Light orange solution was then added dropwise during 2 hrs to a stirred solution
of 116 g 1,4-dimethoxybenzene (prepared from hydroquinone and dimethyl sulphate
in water, not purified, well dried) in 150 ml dry DMF at 100 - 110 deg C (bath),
a calcium chloride guard tube was used. Heating was continued for 3 hrs. Resulting
black mixture was poured onto 1 liter of ice-water, neutralized with 20% NaOH
(pH = 7-8) and extracted with CH2Cl2 (3 x 150 ml). Combined extracts were washed
with 100 ml water, dried over Na2SO4 and distilled at atmospheric pressure (bath
temp. lower than 80 deg C). Crude black product was crystallized from a mixture of
120 ml ethanol and 80 ml water. Crystallization was finished in freezer. Yield 106 g
pure, light brown 2,5-dimethoxybenzaldehyde (76%, m.p. 52-53 deg C). Isolation
of product by distillation under diminished pressure (b.p. 146 deg C / 10 mm.) should
provide somewhat higher yield, of course.
J.C.S. Perkin 1, 1974, 1353-1354
Note by Rhodium: This procedure does not work as advertised, see Post 299121 (karel: "Revision of post 70528", Chemistry Discourse) for details
(Hive Bee)
02-13-02 04:05
No 268879
116 g 1,4-dimethoxybenzene (prepared from hydroquinone and dimethyl sulphate in water, not purified, well dried)
Does anyone have a ref or write up on this 1,4 DMB synth?
Thanks 
Chemically enhanced.
(Hive Bee)
02-13-02 10:06
No 269004
Instead of starting from hydroquinone, how about toluquinone? After methylation with NaMeSO4, could one procede in a usual toluene--->benzyl chloride--->benzaldehyde?
(Hive Bee)
02-13-02 14:45
No 269084
amalgum yes (that's how to make DOM)
For the methylation, look at Rhod's side, lots off examples, or UTFSM
(Hive Bee)
02-13-02 19:03
No 269177
DOM? Don't you mean DOB or 2C-B? We are going toluhydroquinone---(methylation)--->2
2,5-MeO-toluene---(chloroination)--->
Where does the methyl group on the four posisition come in?
(Hive Bee)
02-13-02 19:22
No 269184
Or, after methylating the toluhydroquinone, one could form the benzyl chloride, react it with KCN or NaCN to get the benzyl cyanide, and reduce that directly to the phenethylamine. If 2C-B was in you dreams of course.
(Hive Prodigy)
02-14-02 03:05
No 269400
DOM could be produced by reacting toluhydroquinone with allyl bromide to form the monoallyl ether, which is subjected to the Claison Rearreangement to regenerate the phenol while producing the allyl chain. Two isomers are produced: one with the allyl chain para to the methyl, and one with the allyl chain meta to the methyl.
Then you simply follow standard procedures for the rest of the synthesis: methylate the phenols, oxidize the alkene to a ketone, and reductively aminate with hydroxylamine.
There are many many other ways. Post 251360 (PrimoPyro: "Shit, can't remember...help me. (chem)", General Discourse)
PrimoPyro
The Water Will Be Your Only Mirror
(Hive Bee)
02-14-02 09:08
No 269544
2,5-MeO-toluene -> 2,5-Dimethoxy-3-methyl-bensaldehyde [wrong I mean 2,5-Dimethoxy-4-methyl-bensaldehyde ] (Vilsmeyer formylation) the Nitromethane and reduction off the 2,5-MeO-3-Me-NP <-- Wrong
--------------edit---------------
Thanks Rhod, ofcourse I ment 2,5-MeO-4-Me-NP
(Chief Bee)
02-14-02 11:24
No 269578
Hest: Vilsmeyer methylation of 2,5-dimethoxytoluene gives 4-methyl-2,5-dimethoxybenzaldehyde.
What is the best way of making 2,5-dimethoxyphenol? Bayer-Villiger of 2,5-dimethoxybenzaldehyde?
(Hive Prodigy)
02-14-02 11:27
No 269579
What's the 2,5-dimethoxyphenol for?
(I don't know of any other ways to make it than the way you already stated.)
PrimoPyro
The Water Will Be Your Only Mirror
(Chief Bee)
02-14-02 11:41
No 269585
New TMA-2 route via claisen rearrangement, and a few other analogs (4-alkoxy TMA-2's).
(Newbee)
02-14-02 21:44
No 269744
hi primopyro,
this sounds interesting. assuming you can alkylate the toluhydrochinone selectively to the 2-hydroxy-5-allyloxytoluene, is there any way of knowing that claisen-rearrangement will give exclusively the isomer w/ allyl para to methyl? since claisen tends to go ortho, one could also obtain the 2-allyl-3-methyl-1,4-dihydroxybenzene.
do you have any idea on this?
otto
(Chief Bee)
02-14-02 21:55
No 269748
Correct. The claisen rearrangement will give about 4:1 ortho:para if there is a free ortho position relative to the allyloxy group.
If you would monoallylate toluhydroquinone without any special reaction conditions (I don't know how though), you would get a mixture of 2- and 5-allyloxy isomers, which if not separated in turn would give a mixture of all three possible p-dihydroxyallylbenzenes if subjected to the claisen rearrangement.
(Hive Prodigy)
02-15-02 04:01
No 269844
Perhaps monomethylate the toluhydroquinone a la Antoncho's new method, then allylate the remaining phenol?
Perhaps the two stereoisomers of the monomethylated toluquinone would have properties as to allow for seperation? i.e. varying solubilities, mp/bp, density, etc.?
Someone with access to the merck index?
PrimoPyro
The Water Will Be Your Only Mirror