Novel Bromosafrole synthesis

[Rhodium]

I got this submission in an email from Berserker.

Easy Bromosafrole Synthesis by Berserker

This is a revolutionary new method to halogenate ketenes with Markinokov selectivity, by reacting them with a phosphorus trihalogenide in the presence of silicon dioxide catalyst. To make others, just substitute safrole with 10 mols of another alkene.

A suspension is made by stirring 5g of SiO2 (silicon dioxide) into a solution of 10 mol safrole in 25ml dichloromethane. To this, add a solution of 4 mol PBr3 (phosphorus tribromide) in 10ml DCM over the space of 10 minutes at room temperature. The solution is then stirred for around 30 minutes. The SiO2 (still in suspension) is filtered out and then washed with 15ml DCM. The combined liquid is washed with a 10% sodium bicarbonate solution, until no more gas is liberated, then twice with brine, and the organic extract is dried with sodium sulfate. The solvent is then allowed to evaporate, giving pure bromosafrole.

Yields vary between 50% and 100%.

The SiO2 is 70-250 mesh powder, or can be prepared by grinding glass into a fine powder, and washing it with acid. Both silicon dioxide and phosphorus tribromide are unsuspicious chemicals, and can be ordered with ease from well-stocked chemical suppliers.

Reference:

Journal of the Brazilian Chemical Society, Vol. 12, No. 5 (2001)

(http://jbcs.sbq.org.br/jbcs/2001/vol12_n5/12.pdf)

[LaBTop]

What a coincidence, see:

Post 108668 (missing)

(dormouse: "Delepine RESULTS in .....  -spiceboy", Novel Discourse), look for all the comments from Danielsan, in MARCH 1999!

Post 108559 (missing)

(dormouse: "chloro, bromosafrole @ room temp in 1 hr  -danielsan", Novel Discourse), chloro, bromosafrole @ room temp in 1 hr -danielsan ,
Rev Drone and BrightStar "nitpicking" on Danielsan, hehhe 19 NOV 1998!

Post 122782

(dormouse: "visciously beating a dead horse: MDP2-Pol, back from the dead  -drone 342", Serious Chemistry), Rev Drone already thinking about epoxides and diols 30 DEC 1998:
"" rev drone
Member   posted 01-06-99 11:29 AM          
--------------------------------------------------------------------------------
I have some amazing ref's using NaOCl and a PTC to oxidize olefins to epoxides and diols -- since both of these compounds are readily isomerizable into the methyl ketone, this is effectively a one-pot-shot. PTC's are the stuff of dreams, and with enough research, I think they could be used to quantitatively catalyze water into wine.
One ref for this procedure is:
JACS 107 (1985) 2000
I have a dozen more, but they're not with me.

Still, this is off-top. You want alcohol oxidations, and alcohol oxidations is what you shall recieve. I'll be back...

------------------
-the good reverend drone ""

http://jbcs.sbq.org.br/jbcs/2001/vol12_n5/12.pdf

  near to plagiarism. LT/

WISDOMwillWIN

[psytech]

Ok, 1mol 3x frozen sassafrass oil ,the color was off yellow. In a 1l flask was added 162g safrole, then 250 DCM, and 50g 200 mesh SiO2. At this point the solution was turbid, with clouds of SiO2 swriling about.  To this stirring solution was added .4 mol of PBr3 in 100ml DCM. After the first 10ml portion of PBr3, the color changed to a deep tan color, the after each 10ml addition, the color progressed to orange, the a reddish pink, but never really red. After the Pbr3 additions,bromo compund was allowed to stir for 30mins. To neutralize the remaining acids, about 200ml of 10% Na Bicarb was added, untill fizzing stopped. The water layer was drawn off. The bromo compound was then washed 2x with brine,this removed a lot of color from the solution, from a reddish pink color to an almost clear, very light tan.Proceeded to distilled DCM from bromo compound, as the DCM, was removed the color of the bromo compoud became progressively darker, not brown but close, still very transparent. I did notice the odor, sort sweet, sort sassy, not sure on my sucess, because at this time im with out a vac pump, will try amination anyway, wish me luck.

[RedMonn_16]

It doesn't take a work of genius to make bromosafrole, unless Rhodium did it of course, but the real problem comes after that step when the secondary carbon to which the bromine atom is attached is undergoing a nucleophilic substitution reaction.  The thermodynamics thereof are just really not that terribly conducive towards receiving a high percent yield of product.  Now, OTOH, if the halogen had been attached to a primary carbon, as could be the case in a DMT synthesis, then that would be another story.  O High Rhodium, may I ask what degrees you have, from what colleges and/or universities and what exactly they are in (physics perhaps)?  You are an excellent librarian I am sure, but you just don't really seem to see the forest for the trees in many instances; however, bromosafrole could be treated with sodium azide and then reduced with NaBH4 in pyridine to yield MDA in decent yields I would imagine.

[Rhodium]

Do you even know what you are talking about? Everybody knows that trying to aminate bromosafrole directly with ammonia or methylamine is doomed to failure or low yields - even Total Synthesis I stresses this point. So - naturally I have never implied that the suggested use of the bromosafrole was direct amination. I have however on several occasions reccommended azide swap followed by reduction.

The literature is full of examples of secondary bromides being transformed into azides in moderate to high yields (75-95%), using a variety of reagents, most commonly sodium azide in an aqueous or alcoholic solvent system, but PTC's and more exotic reagents like trimethylsilyl azide has also been employed. The reaction is usually very clean, and the main side reaction in the azidation of secondary bromides is elimination, so that any starting material not converted to azide can be recovered as the alkene and re-used in another reaction.

So far so good. The next step is reduction of the azide to the amine, and this is one of the most ridiculously simple and high-yielding reductions you can find in organic chemistry, with literally several dozen reducing agents available to do the job. You will have no problem geting 95% yield.

I regret having to inform you that I have no degree whatsoever, I am an autodicact, concentrating on actually learning things instead of spending my valuable time on getting that silly piece of paper.
I have spent several hours each day (on average) for the last ten years studying any texts on chemistry, pharmacology and other interesting science-related stuff I have been able to access - either in books, online or in journals at the university library. Nobody beats me on my own turf.

[RedMonn_16]

Why did my alcohol to halo alkane to amino alkane to nitroethane get filed under Libby (the dead witch's office) and rated as 'insignificant.'  I mean, that particular synthetic outline looks elegant enough to me, and I am apparently too much of a bum to even find a steady means of real income (that is, 'a job').

[Rhodium]

Check out

Post 372701

(Rhodium: "Vogel and Advice", Serious Chemistry) - what I wrote there to pHarmacist is applicable to your post too.