not useful stuff deleted 
5-dimethylheptyl-resorcinol (Olivetol) Synthesis
« on: May 23, 2012, 12:01:46 PM »
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Topic: 5-dimethylheptyl-resorcinol (Olivetol) Synthesis (Read 312 times)
carl_nnabis
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Sydenhams chorea
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Re: Dimethylheptylolivetol Synthesis/desoxy HU-210 nearly done
« Reply #1 on: May 23, 2012, 04:23:28 PM »
I can't see how sodium or aluminium alkoxides can substitute for a Birch reaction?
Maybe do the Birch in another solvent than liquid ammonia? Ethylenediamine perhaps?
Maybe do the Birch in another solvent than liquid ammonia? Ethylenediamine perhaps?
lugh
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Re: Dimethylheptylolivetol Synthesis/desoxy HU-210 nearly done
« Reply #2 on: May 23, 2012, 07:43:09 PM »
The attached article, British Journal of Pharmacology Volume 132, Issue 2, pages 525–535, January 2001 which is freely available online as DOI: 10.1038/sj.bjp.0703827 may be helpful if studied for citations concerning HU-210 
sj.bjp.0703827.pdf
(209.66 kB - downloaded 13 times.)Sedit
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Re: Dimethylheptylolivetol Synthesis/desoxy HU-210 nearly done
« Reply #3 on: May 24, 2012, 03:06:34 AM »
Using very good stirring bubble Gassious Ammonia into Ether or another non-polar solvent with Lithium Finely divided. Blenders can be modified to work like a charm 
.
Once your lithium turns into a golden liquid ( the Ether will look brown if you are still stirring it) you can add your substrate you wish to reduce. This reaction is exactly like that of the birch reduction however it does away with the need for liquid ammonia. Matter of fact elevated temperatures( room temperature) performs the reaction faster then if you chill the Ether.
Sodium has less chance of over reduction due to the fact that there is a competing reaction of hydrogen generation as opposed to reduction.
. Once your lithium turns into a golden liquid ( the Ether will look brown if you are still stirring it) you can add your substrate you wish to reduce. This reaction is exactly like that of the birch reduction however it does away with the need for liquid ammonia. Matter of fact elevated temperatures( room temperature) performs the reaction faster then if you chill the Ether.
Sodium has less chance of over reduction due to the fact that there is a competing reaction of hydrogen generation as opposed to reduction.
carl_nnabis
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Re: 5-dimethylheptyl-resorcinol (Olivetol) Synthesis
« Reply #4 on: September 10, 2012, 04:31:42 PM »
I have deleted all the not useful posts
Im done now with the synthesis so see how it should have looked
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 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. 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, and was extracted using DCM instead, and yielded this time a nearly similiar yield of 1,44g oil.
1,44 of dimethylheptylresorcinol dimethylether were dissolved in 24ml of GAA with 6ml fumingHBr 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 sticky 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 some impurity possibly its monomethylether, that would contribute to melting point and slow hardening once it got molten.
The reagents used so far, as some of them aren´t that common in a clandestine laboratory, have some characteristics that should bee noted.
Methane sulfonic acid is a very strong acid, especially when pure, it can carbonise organic materials like concentrated sulfuric acid. It can be substituted with 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 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
[patent]http://www.patentgenius.com/patent/4131656.html[/patent]
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).
Im done now with the synthesis so see how it should have looked
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 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. 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, and was extracted using DCM instead, and yielded this time a nearly similiar yield of 1,44g oil.
1,44 of dimethylheptylresorcinol dimethylether were dissolved in 24ml of GAA with 6ml fumingHBr 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 sticky 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 some impurity possibly its monomethylether, that would contribute to melting point and slow hardening once it got molten.
The reagents used so far, as some of them aren´t that common in a clandestine laboratory, have some characteristics that should bee noted.
Methane sulfonic acid is a very strong acid, especially when pure, it can carbonise organic materials like concentrated sulfuric acid. It can be substituted with 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 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
[patent]http://www.patentgenius.com/patent/4131656.html[/patent]
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).
carl_nnabis
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Re: 5-dimethylheptyl-resorcinol (Olivetol) Synthesis
« Reply #5 on: September 11, 2012, 12:19:09 PM »
Had 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)
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