THC Synthesis (not extraction!!)

mk-1 · Wed Mar 16, 2005 7:05 am

Alright. So, swim got access for some nice compounds and wants some help in the synthesis of legal THC analogs such as the dimethylheptyl(THCV) analog, as well as the hexyl analog(THCII).
So swim was thinking of going from commercially availbe 5-chloro-1,3-dimethoxy benzene. Swim thought he can next do some form of grignard reaction on this to get 5-alkyl-1,3-dimethoxy-benzene which would bee dimethylated with any form of dimethylating agent.
So swim thought, and cant figure out how to do it. Swims memory and understanding of the grinard mechanism is not complete. So if some1 would help it would bee nice.
Swim thought of maybe reacting hexylbromide with magnesium to afford hexylmagnesiumbromide, but then swim dontknow if this can bee use to attack the 5-chloro position.
Swim also thought of using maybe 1-bromo-3,5-dimethoxy benzene which would need the same reaction to transform into 5-alkyl resorcinol methyl ester.
IF anyone has a better way in their minds swim will bee happy to hear or disucss it Smile

wyndowlicker · Member of the Month

Hey now,

can someone post a workable write up with the most OTC or easier to aquire chems?Thanks.

W.L

Laughing

DrugPhreak · Working Bee

Wow! The strongest analogs are legal? Of course they would apply under the analog act though... for any bees in Amerikkka. Mad

THE MOON RULES --1 · voted for the moon

mk-1, PLEASE GOD COME TO THE GREEN SIDE AND COME TO PSYCOTROPIKAL! We need you at our thc chemistry section! We have an untouched thread dealing with thc-V. If not just double post. There are many people on both sites that are very very interested in delta 5, so.......please

Sandmeyer · Sat Apr 23, 2005 8:10 pm

From the little I know about THC chemistry olivetol is the central precursor to the THC analogs. The below is beautiful Michael addition route to olivetol from aliphatic precursors, the preparation of starting material 3-nonen-2-one is apperantly described in J. Gen. Chem. (USSR), 33, 141-145 (1963): Engl. Translation. The 3-nonen-2-one is also comercailly available but IMO expensive; 50g $43.20 from western compounder.

Methyl 6-n-Pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-l-carboxylate
(2).22 To a solution of 32.4 g (0.60 mol) of sodium methoxide
and 90 g (0.68 mol) of dimethyl malonate in 230 mL of anhydrous
methanol was added portionwise with stirring 75 g (0.48 mol) of 90%
pure 3-nonen-2-one (1). The reaction mixture was then refluxed for
3 h under N2 and allowed to cool to room temperature. The solvent
was distilled under reduced pressure and the residue dissolved in 350
mL of water. The slurry of white crystals and the almost clear solution
was extracted with 3 X 80 mL of CHC13, the aqueous acidified to pH
4 with concentrated HC1 and the white precipitate allowed to stand
overnight and filtered. The crystals were dried at 50 "C under high
vacuum for 5 h tCJ yield 106.5 g (92%) of 2, mp 96-98 "C.

1-n-Pentyl-3,5-dihydroxybenzene, Olivetol

To an icecooled
solution of 58.4 g (0.24; mol) of 2 dissolved in 115 mL of dimethylformamide
was added dropwise with stirring a solution of 37.9
g (0.23 mol) of bromine dissolved in 60 mL of dimethylformamide.
At the end of the addition (ca. 90 min) the reaction mixture was slowly
heated to 80 "C during which time the evolution of carbon dioxide
became quite vigorous. The reaction was maintained at this temperature
until the gas evolution had ceased and was then heated to 160
"C and held at this temperature for 10 h. The DMF was removed
under reduced pressure and the residue treated with 80 mL of water.
The mixture was extracted with 2 X 250 mL of ether and the ether
solution washed with water, 2 X 80 mL of a 10% solution of sodium
bisulfite, 2 X 80 mL of a 10% solution of acetic acid, and then again
with water. The ether solution was dried (Na2S04) and the solvent
removed under reduced pressure to give 46.8 g of a viscous oil. The
oil was distilled through a 12 in. Vigreux column (314 in. diameter) to
give 30.3 g (69.3%) of 3, 95% pure by VPC. An analytical sample recrystallized
from ether gave: mp 85-86 "C;

J. Org. Chem., Vol. 42, No. 21, 1977

IndoleAmine · Dreamreader Deluxe

scarmani · Sun Apr 24, 2005 1:52 am

HU-210 is a dimethylheptyl analog of THC which is active at less than 100 micrograms and can last over 24 hours.

It is Schedule 1 in the US according to the following sites:

http://www.caymanchem.com/app/template/Product.vm/catalog/90082/a/z
http://www.sigmaaldrich.com/ProductLookup.html?ProdNo=H7909&Brand=SIGMA
http://www.tocris.com/shop/DispProd.php?ItemId=2257

"HU-210 is a synthetic cannabinoid that was discovered around 1988 in the group of Dr Raphael Mechoulam at the Hebrew University. HU-210 is 100 to 800 more potent than natural THC from Cannabis and has an extended duration of action. HU-210 is the (+)-1,1-dimethylheptyl analog of 7-hydroxy-delta-6-tetrahydrocannabinol. The abbreviation HU stands for Hebrew University." - http://www.marijuana.com/wiki/HU-210

You can find a few relevant papers at http://www.streamload.com/scarmani/Research/Cannabinoid

Sandmeyer · Sun Apr 24, 2005 3:49 am

there is some interesting review-kind of info on the the subject here: http://www.biotrend.com/pdf/cannrev.pdf

scarmani, do you know how importnant the stereochemistry is activity-wise?

scarmani · Sun Apr 24, 2005 7:47 am

I believe for THC analogs, stereochemistry is very important. So for example, HU-211 is a stereoisomer of HU-210 which is neuroprotective, but has no appreciable psychoactivity.

http://www.drugabuse.gov/pdf/monographs/79.pdf is a definitive resource which covers a number of points about the SAR of cannabinoids, and specifically addresses stereochemical requirements.