Rhodium (Chief Bee)
02-04-03 04:13
No 404199
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Could somebody who can read french take a look at ../rhodium/pdf /archive/fr1549154.pdf and tell me if there is any synthetic procedures of interest in it? I found a note where I had written that I should check it out, but not why... crazy
(Hive Bee)
02-04-03 11:28
No 404331
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Reading French is not that difficult Rh cool. Understanding is a completely different aspect wink. Things displayed in red are added by myself.

Phenylethylamine derivatives and their preparation

Invention: Josef SCHMITT

We know that several beta-phenylethylamines (PEA) exhibit a variety of sympathomimetic properties, anorexic and cardio-vascular activity - hypertensive activity in general. The following invention's aim was to develop a series of new PEA derivatives that predominantly or only showed anorexic properties. Also, we wanted to create new intermediary synthesis products, wich could be therapeutically interesting.
The further mentioned substances agree with the following structure: Look at first molecule drawing in the text
- X can be hydrogen, or an alkyl or acyl group having 1 to 5 C-atoms;
- Y1 and Y2 can be hydrogen, or both together one oxygen atom;
- R1, R2 and R3 can be hydrogen or an alkyl group having 1 to 5 C-atoms;
- R4 stands for an alkyl group having 2 to 6 C-atoms.
It should be clear now that we are talking about amido-ketones, amino-ketones and amines lacking a carbonyl group.
[...] To synthesize the amido-ketones [...], an amine of the following formula (2nd structural formula) can be reacted with a carboxylic acid derivative (for instance their anhydride or chloride) having 1 to 5 C-atoms, in order to acylate the amine function and react the so-formed amide with R4-CO-Cl, according to Friedel-Crafts.
Useful precursors for this invention are amphetamine, N-methylamphetamine and N,N-dimethylamphetamine. Since the acyl radical, which has to be 'fixed' on the amine function, and the R4-CO acyl radical, which has to be 'fixed' in para position on the phenylic nucleus, are the same, both reactions can be performed in one pot. As will be indicated, the Friedel-Crafts catalyst, e.g. AlCl3, can be added in exces to the reaction mixture, which also contains RCOCl [...] weird French [...].

[...] Example 1 - p-valeryl-N-valeryl-methamphetamine; R1 = R3 = CH3, R2 = H, R4 = CH2CH2CH2CH3, X = COCH2CH2CH2CH3; amido-ketone. I in the patent --- To cooled and stirred methamphetamine (14.9 g, 0.1 mol), 60.25 g (0.5 mol) valeryl chloride is added over 30 minutes. The ice bath is removed and over one hour, 53 g (0.4 mol) pulverized anhydrous AlCl3 is added in small portions. The reaction is continued for another 2 hours at ambient temperature and then poured over a mixture of fine ice and HCl. The mixture is extracted with EtOAc and the organic layer washed with water, sodium carbonate solution and finally with water. The mixture is dried over sodium sulfate and the solvent evaporated. The residual oil is distilled to obtain substance I (21.3 g, BP/0.1 mmHg 180-210 C)
[...] Example 2 - p-valeryl-N-propionyl-methamphetamine; R1 = R3 = CH3, R2 = H, R4 = CH2CH2CH2CH3, X = COCH2CH3; amido-ketone. II in the patent --- (a)A mixture of one part of methamphetamine and three parts of propionic anhydride are refluxed for 2 hours. The mixture is concentrated to dryness and the residual oil distilled to obtain the propionic amide of methamphetamine. BP/14 mmHg = 165-167 C (vapour temperature) (b)To a stirred mixture void of humidity of 20.5 g (0.1 mol) of the previously described amide and 60.25 g (0.5 mol) of valeryl chloride, 53 g (0.4 mol) AlCl3 is added over one hour. The reaction is allowed to continue during the night, and the formed complex is decomposed as indicated in example 1. Separation of the target compound as indicated in example 1 as well. Distillation occurs at 180-205 C, 0.1 mmHg. This yields 26.5 g of a yellowish oil, being substance II. Yield: 91%. (c)To 240 g (1.8 mol) AlCl3, a solution of 123 g (0.6 mol) N-propionyl methamphetamine in 500 mL petroleum ether is added while stirring. This mixture is stirred for 15 minutes, after which a solution of 79.8 g (0.66 mol) valeryl chloride  in 100 mL petroleum ether is added. The mixture is refluxed for 15 hours. The formed complex is decomposed by pouring the reaction mixture over a combination of fine ice and HCl. The organic phase which is obtained after extraction with ether, is washed with water and dried over sodium sulfate. The solvent is evaporated. The residual oil is distilled to yield a yellow oil (141 g). BP/0.1 mmHg = 180-205 C, yield = 82%. The obtained substance is identical to the one isolated in 2b.
[...] Example 6 - p-butyryl-N-butyryl-amphetamine; R1 = CH3, R2 = R3 = H, R4 = CH2CH2CH3, X = COCH2CH2CH3; amido-ketone. VI in the patent --- (a)Similar synthesis as in example 1, except that methamphetamine is substituted for amphetamine and valeryl chloride for butyryl chloride in their corresponding amounts. Substance VI is obtained in 41% yield as a yellow oil. BP/0.1 mmHg = 200-225 C. (b)Working in a similar way as in example 2b, but replacing the propionic amide of methamphetamine by its butyric amide (BP/15 mmHg = 185-187 C, vapour temperature), and substituting valeryl chloride for butyryl chloride in their corresponding quantities. Yield: 85% of substance VI. Characteristics were similar to the product obtained in 6a.

The aim of the patent is simple: develop amphetamine derivates which display anorexic properties. The substances they used in their study are (meth)amphetamines with substituents on the phenyl ring in the para-position. To incorporate the new para-substituents, a Friedel-Crafts like procedure is developed. If I remember correctly, there are some PEAs and amphetamines with alkyl groups in the para-position. There are tricks to get rid of that C=O function, aren't there... I'm not a native French speaker, so any corrections to possible mistakes are welcome. But still, I'm pretty sure the general outline of the patent has been interpreted correctly tongue.

Abusus non tollit usum
(Hive Addict)
02-04-03 13:09
No 404345
      thanks, GC_MS :)  Bookmark   

usually the french texts get stuck with me. tongue

> As will be indicated, the Friedel-Crafts catalyst, e.g. AlCl3,
> can be added in exces to the reaction mixture, which also contains RCOCl [...] weird French [...].

, that is adding the Friedel-Crafts catalyst, e.g. AlCl3, to the reaction mixture containing the acid chloride, in excess as to what is needed for the first reaction, so that then the second reaction takes place.

(ok, that english is somewhat clumsy. what they say: you have the reaction mixture with the acid chloride, you add more AlCl3 than is needed for the first reaction, so that the second one takes place after the first one is finished)
(Hive Bee)
02-04-03 14:12
No 404355
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It is about what I thought they were saying, although the grammatical construction looked weird and too confusing for me. So I prefered to say "weird French" instead ;)

Abusus non tollit usum
(Chief Bee)
02-04-03 21:47
No 404457
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Thanks. It is indeed novel, but at the same time pretty odd... But oh well, It might be useful one day...