Author Topic: Bromination of amphetamines  (Read 923 times)

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Bromination of amphetamines
« on: January 10, 2002, 04:28:00 AM »
Couple questions about brominating amphetamine freebases.

A solution of 3,4-methylenedioxyamphetamine (MDA) in acetic acid was treated with elemental bromine, generating the hydrobromide salt of 2-bromo-4,5 methylenedioxyamphetamine"

"To a well-stirred solution of 24.8 g 2,5 dimethoxyphenethylamine in 40mL glacial acetic acid, there was added 22 g elemental bromine dissolved in 40 mL acetic acid.  After a couple of min, there was the formation of solids and the simultaneous evolution of considerable
heat."


When Shulgin is brominating 2C-H  or MDA in HOAc it looks like he is using 2X+ equivalents of Br, he also mentions what reads to me like a simultaneous generation of HBr which  forms the HBr salt at the same time the ring is being brominated.

Do i interpret correctly? How is the HBr being formed? where is the H coming from? How can this be prevented?

he comes right and admits it here "To a well-stirred solution of 31 g 2,6-dimethoxytoluene in 200 mL CH2Cl2 there was added 11 mL elemental bromine, a portion at a
time.  There was a copious evolution of HBr and the color gradually faded from deep red to straw."


Yet in beakers synth he is only generating 1.1 equivalents of Br.

"43.8g (94%) of 2CH Hydrochloride basifiied , which was dissolved in 500 mL of 3:1 AcOH/H2O. The rxn was cooled to 0C in an ice/water bath. 37.3g of 48% aq. HBr was added,   followed immediately by 23.8g of 30% H2O2"

Why does his variation not require the extra equivalent of bromine? Is no HBr being generated in this rxn? Is the ring brominated before HBr salt can be formed, or does the water present inhibit the HBr generation?

Osmium mentioned brominating in aqueous HBr, and all those vanillin bromination recipes are only using 1.1 equivalents, no HBr generation there either

Last question, any reason to think these methods would fail to brominate the 6 position in an otherwise ring-saturated amphetamine?

thanks in advance

Rhodium

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Re: Bromination of amphetamines
« Reply #1 on: January 10, 2002, 04:44:00 AM »
When you brominate a phenyl group with Br2, a hydrogen is removed from the ring and combines with one of the Br ions, and the other sticks to the ring.

Osmium

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Re: Bromination of amphetamines
« Reply #2 on: January 10, 2002, 11:44:00 AM »
The HBr produced can then be used to regenerate more Br2:

2HBr + H2O2 __> Br2 + 2H2O

This means you can brominate without having access to elemental bromine at all, by generating the Br2 in situ. All you need for this is either HBr or NaBr and a strong acid, and some H2O2 added dropwise.
Yields might suffer, depending on ratios chosen.

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Re: Bromination of amphetamines
« Reply #3 on: January 11, 2002, 02:58:00 PM »
if i understand correctly then, beaker's synth uses less bromine because the presence of hydrogen peroxide recycles  evolved HBr back to Br2 before it can form a salt, so he isn't wasting an equivalent of Br by forming the HBr salt?

in beakers thread Osmiun, you suggest adding the H2O2 dropwise, this is to prevent an excess of H2O2 from being present? How damaging would excess H2O2 be in this rxn?

could 2Br2 + H2O2 be added simulatneously, or are they likely to react in the sep funnel?

is there any advantage to generating the Br2 in situ besides avoiding the handling of a loathsome chemical?

All these proceedures start from a freebase, yet they are using acids as solvents forming the acetates of these freebases, why bother freebasing the amine at all, why not simply brominate the HCl or SO4 salt directly?

thanx again