Verdict on the Bromosafrole route?

sony · Sun Jul 10, 2005 5:09 pm

Found more information on saccharin being used in the gabriel synthesis in the hive files:

https://www.synthetikal.com/hiveboard/novel/000534482.html

loki · guinea pig

man that is a nice synthesis. so, if i am reading that right, one can form the tertiary amine of saccharin, with a methyl halide and then react this in the same way. the selectivity for producing mono-alkylated amines is very desirable.

regarding tetrabutylammonium bromide, that microwave synth is so lovely it's obscene, so making tetrabutylammonium bromide would be very much something that someone interested in this amination method would like to know about. any clues on how to get it. it'd be a terribly useful thing to know how to make for doing PTC reactions as well.

the nicest thing of all is the fact that this gabriel reagent is so easy to find... presumably one could a/b extract it from sachharin sweetener from the supermarket?

sony · Sun Jul 10, 2005 7:06 pm

Exactly my thoughts Smile

rhodium has a preparation of TBAB ( http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/tbab.html )

But most of those reagents don't seem to bee over the counter either.

In regard to saccharin sony wonders about how mild exactly the removal of the protecting group would be.

The abstract from the hive archive states : Much milder and rather specific conditions can be used for the final deprotection than are required for phthaloyl, and alkylation can, if required, be carried out twice, in which case also secondary amines are obtained. Several of the novel reagents are easily made, and they can be alkylated in the same way as phthalimide or its potassium salt, but neither strong acid or base nor hydrazine is needed to cleave off the protecting group(s).

Makes sony wonder what exactly is needed to cleave off the protecting group? Perhaps a weak acid/base would already do the trick then ?

loki · guinea pig

i thought that meant that a weak agent (weak acid or base) would do it, when i read it (eg ammonia)

sony · Sun Jul 10, 2005 11:11 pm

The Gabriel-Colman Rearrangement in Biological Systems: Design, Synthesis and Biological Evaluation of Phthalimide and Saccharin Derivatives as Potential Mechanism-Based Inhibitors of Human Leukocyte Elastase, Cathepsin G and Proteinase

William C. Groutas, Lee S. Chong, Radhika Venkataraman, Jeffrey B. Epp, Rongze Kuang, Nadene Houser-Archield, and John R. Hoidal
Bioorganic & Medicinal Chemistry, Vol. 3, No. 2, pp. 187-193, 1995

FullText

ApprenticeCook · DILLIGAF

In the WD thread psycokitty was talking about sacchrin.
In the journal i uploaded they used trifluoroacetic acid to cleave.
Nice find in the hive archives sony.

TBAB can be made although it is very fidly, remember you only need a catalytic amount, i had plans on this for the eugenol --> safrole method with AlI3 and TBAB.
1-Butanol is easily bought, dichromate oxidation to butanal (or buy butanal) under distillation to prevent over oxidation. Use this in the similar method to making methylamine to make tri-butylamine (dry conditions, 6x molar excess of butanal to ammonium chloride? i think).
1-Butanol --> 1-bromobutane (HBr?) then this together with tributylamine refluxed in acetonitrile produces TBAB.
Acetonitrile can be bought or formed from the dehydration of acetamide with P2O5 which can also be bought.

Thoughts?
-AC