Oh my beeloved brethren!
As many lately noted, the chemistry forums run somewhat shallow these days... If not for Barium, it’d stop altogether, I guess :) . Perhaps, that is the reason that even some of the best-winged have turned to the Couch to engage into activities otherwise seen only from people of a plebic mindset :) :P :o
Anyways, i thought i'd pull smth curious from the depths of my HD so as to ease the atmosphere a little. It's certainly a somewhat complicated synth and requires some expensive/sparse catalysts, but the chemistry is neat enough to keep you amused, i hope :)
Especially that last step, Hoffmann degradation of Ph-propionamide to the PEA.
Patent US6255528 (http://l2.espacenet.com/dips/viewer?PN=US6255528&CY=gb&LG=en&DB=EPD)
Fluorine-containing phenethylamines are obtained in an advantageous manner by reacting fluorine-containing bromobenzenes with acrylamide in the presence of a palladium catalyst, hydrogenating the resulting arylacrylamides catalytically and then rearranging the arylamides obtained.
Example 1
275 ml of dry dimethylformamide were flushed with nitrogen for 1 hour. 100 g of 1-bromo-4-(trifluoromethoxy)-benzene, 29.4 g of acrylamide, 101 mg of palladium(II) acetate, 216 mg of triphenylphosphine and 67.8 g of sodium acetate were then added successively, and the mixture was stirred at 130.degree. C. for 20 hours. After cooling, the mixture was filtered, the filtrate was concentrated, the filter residue was combined with the concentrated filtrate and the mixture was suspended in 200 ml of water and filtered again. The resulting filter residue was washed with 200 ml of n-hexane and air-dried. This gave 84 g of 3-[4-(trifluoromethoxy)-phenyl]-acrylamide. According to GC, stated in area percent, the product was 95.9% pure. This corresponds to a yield of 83% of theory.
Now, from the patent it isn't clear if this condensation is specific for fluorine-substituted nuclei - has anyone ever seen smth similar performed on other bromobenzenes?
Example 2
In a stirred autoclave, 250 g of the 3-[4-(trifluoromethoxy)-phenyl]-acrylamide obtained according to Example 1 were initially charged dissolved in 1250 ml of tetrahydrofuran, 6.2 g of palladium-on-carbon (10% by weight) were added, and the acrylamide was hydrogenated at 50.degree. C. and a hydrogen pressure between 5 and 10 bar until the reaction had gone to completion (3 hours). The catalyst was then filtered off and the solvent removed by distillation. This gave 221 g of 3-[4-(trifluoromethoxy)-phenyl]-propionamide. According to GC, stated in area percent, the product was 98.1% pure. This corresponds to a yield of 86% of theory.
Obviously, there are other then pressure hydrogenation ways to reduce that double bond, not touching the amide function. Anyone has propositions? Would ordinary NaBH4 do the job?
Example 5
(in the previous two examples they did the same rearrangement under different conditions, this one having by far the best yield.)
21.1 g of sodium hydroxide and 20 g of 3-[4-(trifluoromethoxy)-phenyl]-propionamide, prepared according to Example 2, were initially charged in 70 ml of water, and 15 g of bromine were added dropwise at room temperature. The mixture was then heated under reflux for 3 hours. The reaction mixture was subsequently admixed with 200 ml of water and worked up and purified as described in Example 3. This gave 12.9 g of 2-[4-(trifluoromethoxy)-phenyl]-ethylamine which distilled over at from 84 to 86.degree. C. and 10 mbar. According to GC, stated in area percent, the resulting product was 99% pure. This corresponds to a yield of 72% of theory.
As it has probably become by now evident to most of the bees (yes, Ba, I’m writing this specifically for you! ;) ), such posts more-often-then-not get NO responses at all ;D – well, such is life, I guess :) . So, please, don’t bother replying to this, I’m quite content with my silent submission of knowledge ;D ;D ;D .
[laugh][stoned],
Antoncho