Psychedelic Cathinone Analogs

Has anyone given any thought into this? Creating Psychedelic CATS sound like a fun thing to do. Here are some possibilities: 3,4-methylenedioxy-N-methyl-cathinone - MDMA 4-bromo-2,5-dimethoxy-cathinone - DOB 4-iodo-2,5-dimethoxy-cathinone - DOI 4-methyl-2,5-dimethoxy-cathinone - DOM 3,4,5-trimethoxy-cathinone - TMA 2,4,5-trimethoxy-cathinone - TMA-2 N-ethyl-3,4-methylenedioxy-cathinone - MDE Well you could go on and make CAT versions of every phenethylamine and amphetamine. What about Indoles? Would that double-bonded oxygen in the beta position make any difference with DMT or AMT? Would 3,4-dihydroxy-cathinone work in my biosynthesis theory described in "TMA production with Mescaline-containing Cactii" http://hive.lycaeum.org/ubb_board/Forum1/HTML/002634.html Any and all comments welcome. Laters, Nemesis ------------------------------------------------------------------------------- xxx: The Cathinone-derivates 1-(1,3-Benzodioxol-5-yl)-2-(pyrrolidin-1-yl)propan-1-on and 1-(Phenyl)-2-(pyrrolidin-1-yl)propan-1-on are forbidden drugs contained in the german Btmg list since 1998. Somwhere someone seems to think that these are psychoactive and good... ------------------------------------------------------------------------------- xxx: I agree completely with you, Osmium. That IS truly very fascinating because a-bromopropiophenone is commercially available and VERY easy to synthesize. It is without a doubt that the amine used to make the aformentioned cathinone derivative -- the second one mentioned by Jesomina -- is perfectly legal to obtain AND is probably not as volatile as some of the other lower order amines meaning that the substitution reaction is probably really quite facile. Tell me more. I am DEFINITELY all ears. Wow. - - - - - Wow again! Those fucking Germans seem to be paving the way for psychedelic experimental drug legislation. Some of the proscribed shit on their list is down-right wierd! Anyway, I dug through my little cathinone research file cabinet and found some interesting stuff: As for the 3,4-methylenedioxy ring substituted analogue, I just don't know. But in regard to the simple pyrrolidino cathinone analogue, well, it was developed originally as an appetite suppressant drug and according to a patent that I have which details to a limited degree the pharmacology of several cathinone analog drugs, it was way up there in preference to regular old amphetamine along with the main vein of the paper: diethylcathinone, more popularly know as diethylproprion, an FDA approved drug for appetite suppression. Anyway, here the synthesis for it: First, one starts with a-bromopropiophenone. IF one does not have this precursor then it will have to be made from readily available and CHEAP AS SHIT propiophenone. There are many ways to effect the tranformation of propiophenone to a-bromopropiophenone but the best of the lot is as follows: Taken from JOC vol. 29, 1964, pp3459-3461. Here is a general review of the process for brominated ketones (particularly acetophenones) with CuBr2 in refluxing 1:1 ethylacetate/chloroform solvent. "General Proceedure for the Heterogeneous Bromination Using Copper (II) Bromide -- The copper (II) bromide was finely ground, without drying, in a mortar and pestle to ca. 80 mesh to ensure a large surface area for reaction. Copper (II) bromide (0.050 mol) was placed in an erlenmeyer flask fitted with a reflux condenser, and ethyl acetate (25 mL) was added and brought to reflux on a magnetic stirrer-hot plate. The compound to be brominated (0.030 mole; it is advisable to use a slight excess to avoid the possibility of dibromination)was dissolved in or diluted with hot chloroform (25 mL) (or an additional 25 mL of ethyl acetate if the compound was not solutble in chloroform) and added to the flask. The resulting reaction miture was refluxed with vigourous stirring to ensure complete exposure of the copper (II) bromide to the reaction medium until the reaction was complete as judged by a color change of the solution from green to amber, disappearance of all black solid, and cessation of hydrogen bromide evolution. With numerous compounds the bromination was estimated, form the composition of the mixed copper bromides recovered, to be 90-95% complete in 30-60 min even though the deep green color persisited much longer. The color could be removed by decoloration with Norit A after removal of the copper (I) bromide by filtration. An induction period which varied with the starting material was observed in each case. The copper (I) bromide was collected by filtration and washed well with ethyl acetate. Recovery of copper (I) bromide was 96-100% in every case. The solvents were removed form the filtrate under reduced pressure, except when the product had a low boiling point, a property which required fractional distillation.
That was the general proceedure. There was one paper I found which used propiophenone as an experimental example andddddddd -- wouldn't you fucking know it, I don't have it with me. But the yields were in the range of 90-95% using the same technique with only a slight variation where they bubbled nitrogen into the reaction matrix (presumably to flush out the formed hydrogen bromide) and the time-frame was approximately 5-6 hrs. I'll post the details tommorow.
Anyway, once you have your a-bromopropiophenone you can go one of two ways. The inconvenient way is where you must isolate your a-bromopropiophenone first to then use in the following reaction (tedious and smelly unless, of course, you have a-bromopropiophenone already made): Taken from CA vol.56, 2384 g and/or US Patent # 3,001,910 Sept 26, 1961:
Keep in mind that a-pryrrolidino-propiophenone is one of their experimental models but for the experimetal reaction example, they use diethylamine to make diethylamino-propiophenone. Substituting pyrrolidine for diethylamine in this reaction will yield the desired a-pyrrolidino-propiophenone.
"1145 g of a-bromopropiophenone and 850 g of diethylamine are combined under stirring and heated on a water bath to boiling. The precipitate is filtered off under suction and washed with benzol (benzene). The filtrate is shaken up with aqueous hydrogen chloride, the aqueous solution made alkaline and etherfied. The solution freed of the ether is fractionated. The boiling point (6 mm) is 140 deg C and the yield 800 g. The base is dissolved in acetic ester (ethyl acetate?) and precipitated with isopropanolic hydrogen chloride. After suction filtration and washing with ether the yield is found to be 750 g (80%) and the melting point 168 deg C."
A much better and conventient way to go is to start right where the synthesis of a-bromopropiophenone in refluxing ethyl acetate/chloroform left off:
Substituting pyrrolidine for pyridine will yield the desired a-pyrrolidino- propiophenone. "Preparation of the Substituted 1-Benzoylpyridinium Salts -- The pyridinium bromides could be prepared directily form the filtrate containing the crude a-bromo ketone by addition of a slight excess (0.03 mol) or pyridine followed by heating on the steam bath. An alternate proceedure was to remove the chloroform-ethyl acetate under reduced pressure and dissolve the crude a-bromo ketone (lacrymatory!!!!) in acetone before addition of the pyridine. The latter method sometimes gave crude products which were less discolored and had higher melting points. Both methods gave good yields." I would guess 24 hours would be good enough to effect the desired transformation. Probably less would be needed. One could easily guage the progress of the reaction by observing the slow deposition of pyridine salt. Also, there is no fear of significant side product formation as the nature of the a-pyrrolidino-propiophenone stucture obviates any formation of pyrazine contaminant. If effect, a-pyrrolidino-propriophenone should be the only material recovered. Most definitely this synthesis is ideal as one goes directly from commercial propiophenone to final product a-pyrrolidino-propiophenone without the use of vaccum distillation in what is basically a "one-pot" process. As for the dosage, I don't know. The tablets that were to be manufactured, according to the patent, ideally would contain 25 mg each of product. These were to be taken at each meal each day, making the daily dose 75 mg on average. Side effects were a temporary lowering of blood pressure, with the desirable lack of any observed hypertensive response (Good for me!!!) - - - - -
Okay, I found the reference wherein they detail the specific synthesis of a-bromopropiophenone via the CuBr2 refluxing ethylacetate/chloroform solution.
Taken from: JOC vol. 40, no. 13, 1975 pp1990-1992. "Iodide Catalysis of Oxidations with Dimethyl Sulfoxide. A Convenient Two-Step Synthesis of a-Diketones from a-Methylene Ketones."

I quote:
"Of the many ways to a-brominate ketones, we have had uniformly excellent results with cupric bromide in refluxing chloroform-ethyl acetate."
Here is the general proceedure that they used: 2-Bromocylcododecanone is given as the experimental example.
"2-Bromocylcododecanone. Cyclododecanone (9.1 g 0.050 mol) chloroform (50 mL), and ethyl acetate (50 mL) were placed in a 250 mL three-necked flask equipped with magnetic stirrer, nitrogen inlet tube, and reflux condenser. Powdered cupric bromide (22.3 g, 0.10 mol) was added in small portions over a 2 hr period, with the reaction mixture maintained at 75-80 deg C while a constant stream of nitrogen gas was bubbled through the reaction solution. The green color from each portion was allowed to dissappear before the next portion was added. After the addition was completed, the solution was heated for 1.5 hrs until the green color and dark cupric bromide dissappeared, cooled, and filtered, and the colorless solid cuprous bromide was washed with 25 mL of chloroform. The combined filtrate and washings were rotarty evaporated and the oily residue was redissoled in 200 mL of ditheyl ehter, washed with water (50 mL), 5% sodium bicarbonate (2 tms 50 mL), and brine (50 mL), then dried over sodium sulfate. After filtration, rotary evaporation of solvent, and cooling (-10 deg C), the resulting oil solidified to give cream-colored crystals (11.8 g, 90%) of 2-bromocyclododecanone. "a-Bromopropiophenone (an oil) was prepared on the 100 mmol scale (addition 1.5 hr, stirring 1.5 hr): yield 95%; bp 64-66 deg C (1 mm Hg) [lit. bp 110-111 deg C (3 mm Hg)]." According to table I, the reaction using propiophenone was 5 hrs in total with a 95% yield. - - - -
For anyone who's interested, Table II from JOC vol 29, 1964 pp3460 indicates that the yields for various a-pyridino-acetophenones were in the range of 66-99% which stongly suggests that going from the refluxing ethyl acetate/chloroform phase immediately to substition with the pyrrolidine is the best and safest way to go. No one will like handling lachrymatory a-bromopropiophenone, so the above modification makes for a simple transition from starting material to end product. I wonder though if the precipitated salt is the desired product or simply the salt of pyrrolidine itself? Or even if there is any precipitated salt? Anyone have any best guesses to offer? No? Well, if I had to suggest a way out of the above problem I would say that distillation of the chloroform would be in order (so that the only solvent present would be ethyl acetate). This would then be followed by a basic wash (25% NaOH), a simple water wash to neutrality, and then a back-extraction with 10% HCl, which would then be separated, basified, the final product then being extracted into a suitable solvent and bubbled with dry HCl gas to precipitate the hydrochloride. Who knows though? Maybe the solvent can just be evaporated to yield a crystalline base.