First a tertiary alcohol was prepared, 2-methyl-2-octanol in a yield of nearly 26 gram made out of a grignard reagent prepared from 4,9g Mg-dust and
33g 1-hexylbromide, and after cooling reacted with 12g acetone solvated in a bit ether then let stood overnight. All reagents used are 0,2mol, solvent
used was very dry Et2O. Mg was activated using a tiny piece iodine. Was quenched on a half liter cold water with ice still in it, and not more
extracted beside the starting portion ether, dried with Na2SO4 then.
Next reaction 14,4g of 2-methyl-2-octanol were reacted with 15,5g 2,6-dimethoxyphenol (both 0,1mol) in 25ml methanesulfonic acid with a few ml DMSO as
co-solvent, for about 5hours at 50°C in an oilbath,then after quenching on ice and extraction using two portion of diethylether which was washed with
diluted NaHCO3 solution and dried then over anhydrous sodium sulfate to give 22g 4-(1,1dimethylheptyl)-2,6-dimethoxyphenol as an oil.
1,9g of this substituted phenol (67mmol) were reacted then with an alkoxide made from around 7,5g sodium metal (~0,3 mol) to give dimethylether of
target compound, effecting removal of phenolic hydroxylgroup. First try was made with isobutanol and about 7,7g sodium, the sodium weighed in a hurry,
patted dry of naphtha und cut and added fast as it oxidized in seconds. (becoming opaque on its shiny fresh cut surface)
It reacted very well anyway. After it has dissolved completely it was refluxed a half hour, let cool a bit, as the isobutoxide started to solidify, it
was poured on ice water, acidified and the isobutanol salted out, to give 1,39g of the dimethylheptylolivetol dimethylether as a visous oil, pure
enough on tlc to continue.
The second run was made using nearly 8g sodium and dry ethanol, also 1,9g starting material, and was extracted using DCM instead, and yielded this
time a nearly similiar yield of 1,44g oil.
1,44 of dimethylheptylresorcinol dimethylether from the previous reaction were dissolved in 24ml of GAA with 6ml fuming HBr added, and refluxed in an
oilbath for 8 hours, after which it let cool, then it was poured on 120ml of ice cold saturated brine in a beaker, then left to stir the turbid
solution as a brown gooey looking substance started to harden, and the substance precipiated out. Product was filtered, washed with water twice and
once with very diluted hydrogen carbonate solution to ensure its acid free, then dissolved in 20ml 10% NaOH solution, extracted with 1x10 and 1x5ml
MTBE.
The aqueous phenolate containing solution was made acidic with 15ml 30% HCl and extracted with 2x15ml portions DCM, dried over CaCl2 and distilled off
to give a yellow oil weighing 530mg, hardened on standing to a resinous solid. Melting point 85-90°C. (literature 93-95°C)
On tlc plates some impurity visible possibly its monomethylether, that would contribute to melting point and slow hardening once it got molten.
Unfortunately i dont have the rf values anymore.
Had then a look at the eluotropic serie and chose acetone/diethylether for recrystallisation and was able to raise the melting doing it four times, to
be on a par with the literature cited one now (92-95°C).
But whats left weighed only a bit around 380 milligram, i dont had the necessary small enough equipment to handle this much mechanical loss... and I
was very conscientious rinsing everything mit ether to minimise mechanical loss, but anyway.
Very inconvenient synthesis! Everything comes out just as hard to purifying oil, except the also very discolored final product because a demethylation
with HBr in AcOH really sucks in yield and purity!
The reagents used so far, as some of them aren´t that common in a home laboratory, have some characteristics that should be noted.
-Methane sulfonic acid is a very strong acid, especially when pure, it can carbonise organic materials like concentrated sulfuric acid.
-Diethylether vapours are very explosive, a grignard reaction should not attempted when ones heatplate is not spark proof or even when one has not
proper lights installed as the vapours can catch fire there, unlikely but possible especially without a fume hood.
-Magnesium especially when its fine powder can (thats what the bottle says at least) catch fire in humid air. -Sodium metal does catch fire on contact
with water and its possible even on air exposure due to air humidity. Reacts also violent with alcohols, probably very violent with undried ones.
references for reactions carried out are for the first, second and fourth reaction:
Intermediates for 5-(tertiary alkyl) resorcinol preparation US patent 4131656
US patent 4131656
and for the third reaction it was:
Suter and Weston; J.A.C.S., 61, page 232, (1939).
and Divarin Dimethyl Ether from 3,4,5-Trimethoxy -propiophenone by Yasuhiko Asahina Tokyo, Japan May 20, 1936 translated by Otto Snow and finally yet
another (Asahina Berichte 68B, page 1500, 1935, Asahina Berichte 69B, page 1643, 1936). |
