alkylation of quinones

[poix]

I found this ref on the net: FREE-RADICAL ALKYLATION OF QUINONES: 2-PHENOXYMETHYL-1,4-BENZOQUINONE at

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0890

It say that 1,4 benzoquinone can be alkylated with various acids, producing the corresponding 2-alkyl-quinone minus a methyl ie: benzo + propionic acid lead to 2-ethyl-quinone, acetic acid + benzo lead to toluquinone etc.

The reaction take place in water at 60°, with ammonium peroxydisulfate and silver nitrate as catalyst.

If we reduce the amount of silver nitrate used and take more  reaction time, it may be a valuable process for manufacture of the 2C-E/2C-D/2C-P aldehydes and maybe 2C-TFM with TFA. The yields are not too good but it is better than a F/C acylation I think and it is in one process, not two like F/C.

So I would like to know what you think. 

P iX

[Rhodium]

Oooh. 2C-TFM! Somebody try this synthesis out now!

[Antoncho]

I also remember a mention made by someone that reducing quinones in MeOH leads to dimethoxybenzenes. It's somewhere on Rh's, but no details.

Would bee nice to know the exact proc. to make this yet one step shorter.

Antoncho

[yellium]

I remember that somebody over here performed a reaction like this a long time ago. IIRC, the last step involved `distill and isolate product'. Reaction only produced a shitload of tar and smelly glassware. The room the reaction was performed in smelled like a crackhole for over a month.

[Greensnake]

Uhh, aparently somewhat messy rection, still quite interesting.

Well, seems that yields drop with smaller radicals (in discussion there's said that monoalkylated product should precipitate out to avoid multiple alkylation, with small radicals like Me or Et difference in solubility may be not enough for that) so it may be not too good way for producing Me or Et quinone and other imagined goodies from them.

BUT!!!

It may be worthwile to try to whack in whole ethylamino group in one step using N protected beta alanine or maybe even 2-amino propyl from beta aminobutyric acid.

And that seems a whole lot hotter, dear bees.

[Rhodium]

THAT would be a wundersynth! And just think how cool it would be if the methoxy groups could be tacked on by performing it in MeOH.

Benzoquinone, alanine and methanol to make 2C-H in one step (plus protection/deprotection). Wow.

[poix]

Haven't thought of THAT but it would be pretty cool! When I saw this reaction I know that it had some potential in it, but it is better than I was thinking. I'm laughing out loud!    
One sad thing is that 3-amino-butyric acid is an expensive chemical, but if this reaction work with alanine we will surely find some method to synthetise it for not too much money. Another comment is that if this reaction become popular and some research is done with it maybe we could know if it is possible to put the ethylamine chain in one run, collect the product and then alkylate para to the chain in a second run (with some tweeking of reaction condition) to make 2C-E etc in two step from benzoq, propionic acid, alanine, MeOH (Antoncho find this ref!) etc. And best of all, NO reduction required, NO messy nitroethane synth to do!

I hope some bees will try this rapidly, it may become a killer reaction, psychedelic for the masses!

P iX

[Natrix]

BTW: methoxy group without dimethyl sulfate ->

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0293

[Rhodium]

Methoxy groups can only be introduced like that when there is powerful electron-withdrawing substituents on the ring, such as NO2 and/or CN.

However, with catalytic Cu(I) aromatic bromides and iodides can be substituted with hydroxide or alkoxides to form phenols or phenol ethers.

[PrimoPyro]

Has 2C-M been investigated? The phenethylamine version of DOM.

What about making toluhydroquinone a la Rhodium's site with p-MNT and Al/H+ and then oxidizing it to the benzoquinone. Then alkylating with 3-aminopropanoic acid to add the ethylamine chain, followed by reducing the benzoquinone in methanol to form the dimethoxy diether.

MePh --> p-MNT --> MePh(OH)2 --> MePh(=O)2 --> MePh(=O)2C2H4NH2 --> 2C-M

The aminopropionic acid could be made from succinimide via reaction with NaOH and NaOCl, opening the imide to the mono-amide carboxylic salt, and the NaOCl inducing the Hoffmann hypohalite degradation to form the amine acid salt.

It is simply a modified version of cheapskate's anthranillic acid synthesis.

                                                   PrimoPyro
Vivent Longtemps la Ruche!

[Rhodium]

Has 2C-M been investigated? The phenethylamine version of DOM.

Yes, It is called 2C-D in Pihkal. It seems like a very nice compound.

[halfapint]

Might acetoacetic acid bee a more emphatic condensation reagent than beta-aminobutyric acid? obviate the need for amine protection, etc. Giving hopefully the 2-propanone.
a half a pints a half a pound a half a world a half a round
demimonde, n. Half world.

[Rhodium]

Halfapint: Good idea.

[PrimoPyro]

Same number of steps either way. You exchange amine protection for reductive amination.

halfapint, you sneaky bastard....
Vivent Longtemps la Ruche!

[halfapint]

Reductive amination, though, puts it back on one of our well-trodden paths. We're used to handling ketones; bisulfite purification, though lossy, is mucho handy.
a half a pints a half a pound a half a world a half a round
demimonde, n. Half world.

[Rhodium]

An even better idea is that someone would try out the reaction with BOTH substrates and see which gives the best yields. But that is of course a pipedream of mine...

Hey you out there! If all of you just set aside 10-20% of the time, money and other resources you use to produce the commercial products the old "tried and true" way, and used that for the development of new routes and methods to known compounds (like 2C-B, MDMA, 4-MAR etc) and also some to promising untested compounds (fluoroamphetamines, 2C-TFM, 2C-CN, benzodifuranyl-ethylamines and all the all so active 4-substituted-2,6-dimethoxy-amphetamines/PEA's), this place would be teeming with new and interesting stuff!.

[halfapint]

Antoncho says, "I also remember ... that reducing quinones in MeOH leads to dimethoxybenzenes." Using the acetoacetic acid route to quinone-propanone, reduce with methylamine (or nitromethane) in the methanol. Home free with 2,5-dimethoxyphenyl isopropylamine, a bromination away from DOB.

Suppose that oxone would work, in place of ammonium peroxydisulfate.
a half a pints a half a pound a half a world a half a round
demimonde, n. Half world.

[PrimoPyro]

Holy shit, thats beautiful. halfapint, great thinking.  

Have any other dialkoxy derivatives ever been prepared? Like Diethoxy- or propoxy/isopropoxy-phenylisopropylamine and such brominated derivatives?

                                                   PrimoPyro
Vivent Longtemps la Ruche!

[Rhodium]

It is possible to insert one ethoxy instead of a methoxy in either the 2- or 5-position of a PEA, retaining activity, but losing potency. Two ethoxies abolishes activity (perhaps not with the oh-so-strong DOB), as does higher alkoxy groups in either position. Search Pihkal for "tweetios" (Shulgin's designation for 2-EtO

[PrimoPyro]

Haha, that's funny, Rhodium. Tweetios, I like it.

halfapint: Wouldn't a side reaction in the Al/Hg be imine formation with methylamine and the quinone carbonyls, them being reduced to an amine? If so, that would suck and would have to be prevented.

                                                  PrimoPyro
Vivent Longtemps la Ruche!