HTML by Rhodium
Source: Posted to alt.drugs by Badsector <an26424@anon.penet.fi> on July 22, 1993.
Initially reported as a street drug in the former USSR as ephedrone1. Reports of the use of "Jeff" leading to "numerous" overdose deaths were, it seems, covered up by the former Russian authorities. It has been banned in the USA after several labs were seized in Michigan. It was sold as "Cat", presumably named after the African shrub Khat (Catha Edulis), which contains cathinone2. Methcathinone is related to cathinone as methamphetamine is related to amphetamine, i.e. by N-methyl substitution.
Reliable reports of effects in humans are not known to me. A recent short letter4 in JAMA seems to me to simply to repeat assertions made in the American popular press. In the letter, it is said that users describe "Cat" as better than cocaine and meth. "Typical" doses are described as 0.5-1g and the effects described as lasting six days.
This seems to me to be unlikely. What has been reported may well be equivalent to high dose, methamphetamine abuse on the "speed freak" pattern and is probably not typical.
Animal studies2 suggest methcathinone has ED50 of 1.9µM/kg (0.39mg/kg) , when compared to cocaine's 7.6µM/kg (2.6 mg/kg). This would make it more potent than cocaine by six times in the rat and suggests the human figure of ten times cocaine potency in the human reported on UseNet as been given on Belgium television is not unrealistic. Indeed, this would put it in the same range as methamphetamine, which it may well closely resemble.
Personal communication suggests it may well be simply equivalent to methamphetamine. The bottom line may well be that most CNS stimulants are the same, whether they be cocaine, methamphetamine, amphetamine, 4-methylaminorex or methcathinone. Differing the route of administration is likely to have more effect. Smoking or injecting such drugs leads to rapid build-up of the drug in the blood stream and an intense "rush". This route is more dangerous from a toxicologic point of view and likely to lead to compulsive use. Occasional oral use in social situations is likely to be the least harmful. Some people may find CNS stimulants psychologically addictive.
Oxidation with Potassium Permanganate1
A 2000-mL Erlenmeyer flask, equipped with a magnetic stirring bar, was charged with methylene chloride (200 mL), acetic acid (10 mL) water (100 mL), potassium permanganate (2g) and ephedrine hydrochloride (2g). The solution was stirred at room temperature for 30 min. This was followed by the addition of sufficient sodium hydrogen sulfite to reduce the precipitated manganese dioxide. The aqueous phase was made basic with 5N sodium hydroxide (NaOH) and the methylene chloride was separated. The organic layer was extracted with 0.5N sulfuric acid (H2SO4). Isolation of the acid layer followed by basification with sodium bicarbonate and extraction with methylene chloride (50 mL, three times), removed the product into the organic phase. The solvent was concentrated by rotary evaporation, followed by column chromatography through neutral alumina with methylene chloride. Solvent removal through rotary evaporation produced a colorless liquid which was disolved in hexane. Gaseous hydrochloric acid was bubbled into the hexane to precipitate the amine hydrochloride to produce a 1-g (50%) yield of 2-methylamino-1-phenylpropan-1-one hydrochloride.
Ephedrone, like methamphetamine, processes one asymmetric center. Depending upon the synthetic precursor, l-ephedrine (1R,2S) or d-pseudoephedrine (1S,2R), the product expected would be d-ephedrone (2S) or l-ephedrone (2R), respectively. However, depending on the heat of the reaction or harsh extraction conditions the enolizable ketone will result in a racemic d,l-ephedrone.
Oxidation with Sodium Dichromate3
A solution composed of 0.99g of sodium dichromate and 133g of concentrated sulfuric acid dissolved in 4.46 mL of water is added slowly with stirring to 1.65g of l-ephedrine dissolved in 4.7 mL of water and 0.55 mL of concentrated sulfuric acid at room temperature. The mixture is stirred at room temperature for an additional 4 to 6 hours and then made alkaline with sodium hydroxide soloution. the aqueous mixture is extracted with two volumes of chloroform and then with two volumes of ether. The organic extracts containing the free base of 1-α-methylaminoprophenone are combined, treated with an excess of dry hydrogen chloride and the solvents evaporated. The residual 1-α-methylaminopropiophenone hydrochloride is stirred with petroleum ether, collected and purified by dissolving in ethanol and reprecipitating with ether, mp 182-184°C.
Source: Anonymous post to alt.drugs.chemistry [1997/07/10]
2.62 g of (pseudo)ephedrine HCl was dissolved in 11.6 g glacial acetic acid in a 100 ml beaker equipped with a magnetic stirrer. 20 g of 5.25% sodium hypochlorite solution (Regular Chlorox) was added slowly with stirring. The mixture tested positive to starch iodide paper.
Stirring was continued for 1 hour then sufficient saturated sodium sulfite solution (9.6 g) was added to produce a negative starch iodide test. 50 ml of saturated sodium chloride solution and 15.5 g of ice was added and the solution basified with 50% sodium hydroxide solution (16.7 g). At this point a white precipitate formed and a sweet odor indicative of ketone was observed.
The slurry was extracted with 1x75 ml then 2x50 ml chloroform. The organic phase was dried over sodium sulfate, filtered, and evaporated to yield 2.51 g of slightly yellowish waxy crystalline solid. This was dissolved in 100 ml hot hexane and decanted from a small amount of insoluble material.
Editor's note:
The yellow color might be due to the hitherto discussed CAT dimer byproduct.
Excess HCl gas was bubbled through the hexane solution to form a white precipitate. This was filtered, washed twice with ether and dried to yield 2.25 g (86% yield) of slighly off-white powder with mp 161-171°C.
The crude product was recrystallized from alcohol-ether, filtered and washed with cold ether to yield a bitter white powder with a mp of 179-180°C (final yield 74%).
Melting point of the final product is consistent with methcathinone HCl (lit. 182-184°C). It appears that the oxidation of sec-alcohols to ketone using sodium hypochlorite originally reported in J. Org. Chem. 45, 2030 (1980)can be successfully applied to amines. This procedure is superior to the more traditional chromate & permanganate oxidations in a number of ways, including cost of reagents, no hazardous waste generation, and the easier product isolation resulting from lack of unwanted precipitates in the reaction mixture.
Editor's note:
My reservations about the above post come from the fact that it looks almost exactly like a combination of the permanganate method published by Zhingel et al. in J.
Forensic Sci. 36, 915-20 (1991) (also excerpted in the Methcathinone FAQ 2.2, towards the end of the FAQ) and the hypochlorite method of oxidizing alcohols I've seen in a number of
recent organic chemistry laboratory textbooks. The original poster may just have replaced the steps in the permangante method, with those from the hypochlorite method. Of course,
this may be exactly how the original poster developed a synthetic protocol that maybe does work.
Source: Posted to alt.drugs.chemistry by plop (eluap@cs.uni-sb.de) on April 14, 1998.
The synthesies for cathinone and its derivatives I've seen presented in these newsgroups only uses (nor)ephedrine, but cathinone (and its N-methyl derivative) was prepared long before cathinone was known to be a naturally occuring substance. Because of their chemical instability, the extraction of anything else than freshly picked plant matter only gave by the extaction for basic substances dimeric products (i.e. 2,5-dimethyl-3,6-diphenyl-pyrazine) - thus it was discovered in nature only in the second half of this century.
Fully synthetic Cathinone was first prepared by the german chemist Schmidt, whose synthesis was published in Chem. Ber. 22, 3249-3257 (1889)
The starting material is propiophenone. This can be bought from an ordinary chem supplier. It can also be made by Friedel-Crafts Acylation from benzene with propionyl chloride or propionic anhydride. To make unsubstituted propiophenone, this synthesis is not interesting, but for ring-substituted propiophenones it is very interesing, because cathinone has nearly the same effects as amphetamine. And so, the ring-substituted cathinones could have an nearly equal effect like the ring-substituted amphetamine analogs (i.e. use p-dimethoxybenzene for making 2,5-dimethoxycathinone, the related amph. is 2,5-DMA).
Preparation of Cathinone from Propiophenone
Before treating it with conc HCl, the crysts from #2 can be treated with aq. potassium hydroxide. The resulting precipitate is potassium phtalate. The sol. will be diluted with water and treated with diluted HCl. Then it crystallized as fine nedles with a mp of 140°C. The crysts can used instead of phtalimidopropiophenone on the top of #3.
The intermediate α-bromopropiophenone can be used to prepare Methcathinone as well by allowing it to react with an excess of methylamine. The procedure below is taken from J. Chem. Soc. (London) 50, 2290 (1928)
Preparation of Methcathinone from α-Propiophenone
To make Methcathinone, 0.1 mole of bromoketone was added dropwise to 0.25 mole of methylamine (30% solution in abs. alcohol) over a period of one hour. The reaction flask was immersed in ice water during the reaction and stirring was continued for one-half hour after the addition of the bromoketone.
Then cold, conc. HCl was added very slowly along with some finely cracked ice until the mixture was acidic. If it became warm the product turned very dark in color and a larger propartion of tar war produced. At this point the reaction mixture was orange or red dur to the presence of some bromo ketone that hasn't reacted and to formation of certain tarry by-products. These were extracted with ether from the water layer and the bromo ketone recovered. The water layer was evaporated to dryness in vacuo, treated with a little choroform and evaporated to dryness again to assist in removing the moiture from the rather hard mass. After standing in the vaccuum desiccator for one day, the residue was extracted several times with fresh portions of choroform and each time the insoluble crystals of methylamine hydrochloride were filtered. The choroform solution was then evaporated until it was very concentrated, and acetone was added to cause the crystallisation of the amine ketone hydrochloride. Recrystallisation was carried out by dissolving in a small amount of alcohol, filtering, and adding about twice the vol. of acetone in small portions.
Source: Posted to alt.drugs by <an42976@anon.penet.fi> on July 9, 1994.
Through experience I have compiled the following tips for ppl wanting to do the Cat synthesis. It isn't hard, but the posted synthesis cannot lead to good results becuase of certain ommisions. I don't know if these were omitted deliberately as to stop non-chemists from completing it or whether the author of the original article just forgot. In any case, here are some things you should be aware of.
If you follow these additional comments, you should be able to have success!
The anonymous chemist.
Source: Anonymous posting to alt.drugs.chemistry [1997/06/28]
Despite a recent post to the contrary by Anonymous Artical, there is an easy-to-find academic article with relevant info on CAT cyclization:
Enantiomeric alpha-aminopropiophenone (Cathinone): Preparation and investigation
Berrang-BD; Lewin-AH; and Carroll-FI:
J. Org. Chem. 47, 2643-2647 (1982)
Since there is no academic info on methcathinone (aka CAT), it appears that other posters on the WWW/Usenet have extrapolated the info from this article on cathinone to methcathinone. This artcle contains info on the chemical conditions under which (meth)cathinone is unstable, and will racemize & dimerize (cyclize), and under what chemical conditions (meth)cathinone is stable. It also has info on the 'yellow' cyclization product, 3,6-dimethyl-2,5-diphenylpyrazine of cathinone. Presumably the cyclization product from methcathinone is 1N,3,4N,6-tetramethyl-2,5-diphenylpyrazine.
For those of you who can read technical German, the article below has a more detailed chemical description of the cyclization of cathinone (α-aminopropiophenone) (see esp. pp. 1146ff).
Wandlungen der aminoketone
S. Gabriel
Chem. Ber. 41, 1127-1156 (1908)
A UN review on the chemical composition of khat, including cathinone & the cyclization product:
The Chemistry of Khat
K. Szendrei
Bulletin on Narcotics 32, 5-35 (1980)
Source: Posted by Pugsley to alt.drugs.chemistry [1997/02/01]
Cathinone and Methcathinone both form bright orange cyclization products when in the free base form and sometimes even in basic solution. Chloroform and 1,1,1-TCE however are notable solvents where the bases are stable over extended periods.
Moreover, neither drug form stable salts with anything but mineral acids (although ascorbic acid would be interesting to try, since the otherwise oxidation-sensitive compound adrenaline is stable as the ascorbate).
Thus follows an easy way of characterizing yield without self-administration or complicated testing. Simply take some of the base before final preparation of salt and put it on a white bowl in a warm place. The relative level of bright orange cyclization product shows the relative yield of the synthesis.
Note that the cyclization products are not psychoactive, nor are they easily reverted back into their original amino-ketone forms. Also, the cyclization product smells sickly sweet.
A more complete Methcathinone Synthesis is found in Uncle Fester's Secrets of Methamphetamine Manufacture.
Eye protection is needed and this is done in a well-ventilated area. At least a year of college chemistry lab experience is needed to realize the dangers involved here. This article is for information purposes only.
Cat (Methcathinone) is made by oxidizing ephedrine, while methamphetamine is made by reducing ephedrine. Cat is best made by using chrome in the +6 oxidation state as the oxidizer. Any of the common hexavalent CHROME salts can be used as the oxidizer in this reaction. Some of these are chrome trioxide (CrO3), sodium or potassium chromate (Na2CrO4), and sodium or potassium dichromate (Na2Cr2O7). All of these chemicals are very common. Chrome trioxide is used in chrome plating.
First the chemist dissolves ephedrine pills containing a total of 25 grams of ephedrine hydrochloride OR ephedrine sulfate In distilled water. ephedrine pills usually contain 25mg each of Ephedrine so 1000 pills would be needed. Grinding them up isn't necessary. Let them sit overnight or shake the solution hard for a while. When they're dissolved bring the solution to a gentle boil while constantly stirring so none of it burns. As soon as it starts boiling remove it from the heat and pour through 3 coffee filters layered together to filter out the unwanted filler crap. Usually it is necessary to hold the filters like a bag with the liquid that didn't go through and gently squeeze to get the liquid to go through. The result is an almost totally clear liquid which is the ephedrine extract in water. Throw the mush left in the filter away.
The ephedrine extract is poured into any convenient glass container. Next, 75 grams of any of the above mentioned chromium compounds is added. They dissolve easily to form a reddish or orange colored solution. Finally, concentrated sulfuric acid (it usually comes as 96-98%) is carefully added. If CrO3 is being used, 21 ml is enough. If one of the chromates is being used, 42 ml is needed. These chemicals are thoroughly mixed together and allowed to sit for several hours with occasional stirring.
After several hours lye solution (1 part water, 1 part lye) is very slowly and carefully added dropwise with strong stirring until the solution is strongly basic (pH 11 or more). This strong stirring is to make sure the cat is converted to the free base.
Next, toluene is used to extract the cat. Usually this is done with a sep funnel (separatory funnel, which is a flask with a funnel-shaped bottom and a stopcock (valve) on the very bottom. Sep funnels are used for separating liquids by opening the valve on the bottom and letting the bottom-most layer of liquid drain out.) but a regular glass bottle should be fine but using a plastic cap wouldn't be good. For safety, the bottle would need to be "burped" often anyway to make sure no gasses build up in it. A large eyedropper-type tool could be used to efficiently remove the cat layer. A couple hundred ml's of toluene is added and the container is strongly shaken to make sure the all of the cat free base gets into the toluene layer. Shake until it resembles milk (fine suspended globules of toluene within the water layer). Shake really hard, then allow it to separate. Insufficent shaking will result in poor yield with some undissolved cat base remaining in the spent sludge layer. The toluene layer should be clear to pale yellow in color. The water layer should be orange mixed with green. The green may settle out as a heavy sludge. The water layer is thrown away and the toluene layer is washed once with water and then poured into another container. ("Washed" here means that water is added and the mixture shaken again and separated. The cat free base stays in the toluene layer because it doesn't dissolve in water. Any remaining water-soluble impurities are dissolved into the water layer and not the toluene layer and thus they're "washed" out.)
The cat free base now must be converted to cat salt (methcathinone HCl). Here are 2 methods for doing this.
Methcathinone·HCl (Method 1)
Dry HCl gas is made and bubbled through the toluene solution to turn the cat free base into cat salt (methcathinone HCl). A bottle is selected for holding the gas-producing mixture and a 1-hole stopper will be put in the top of the bottle. One end of a J-shaped glass tube (about 1/4 inch diameter) is pushed into the stopper. This glass tube will reach from the top of the gas-producing bottle down into the bottle holding the toluene-cat mixture. It should reach the bottom of the mixture. Usually a sep funnel is used to add sulfuric acid to the gas-producing mixture through a second hole in the stopper to keep gas flowing. If one doesn't have access to a sep funnel it should be possible to take the stopper out of the gas-producing bottle just long enough to add a little sulfuric acid WHen it's needed to keep gas flowing. Place 200 grams of TABLE SALT into the gas-producing bottle. 35% concentrated hydrochloric acid (reagent grade) is added and they are mixed into a paste. The surface of the paste should be rough with lots of holes poked into it for good gas production. About 1 ml of concentrated (96-98%) sulfuric acid Is added to the paste. This dehydrates thE hydrochloric acid and producES hydrogen chloride gas (** Do not breathe this gas! **). This gas goes out of the gas-producing bottle through the glass tube and bubbles through the toluene-cat solution turning cat free base into cat salt. The cat salt should appear as crystals and after a while the solution should be thick with them. The crystals are recovered by pouring through a filter. The crystals are then dried by evaporating the toluene with gentle heat or under a vacuum. Voila. Pure methcathinone-HCl.
Methcathinone·HCl (Method 2)
That was the "ideal" method. The practical method is to dump the base/solvent solution into a container, add an amount of dilute HCl, shake, shake, shake, measure pH, if it is greater than 7 (pH above 7 is basic), add more acid, shake, shake, shake, and check pH again. Keep it up until the pH is low, staying well below 7 (pH below 7 is acidic), then remove the solvent layer and keep for reuse. Add baking soda To the water layer a little at a time until it stops bubbling when more is added. Check the pH, make sure it is 7 (neutral) or higher. The water is now evaporated away on non-plastic plates or pans and the dried methcathinone HCl can be scraped off with a razor blade. The methcathinone HCl has a trace of sodium chloride (table salt) and an even smaller trace of sodium bicarbonate (baking soda). The baking soda combines with the excess HCl to become table salt. This practical method avoids the mess of producing HCl gas. HCl is a white gas that burns your eyes and nose really badly should you breathe it. It converts upon contact with water into hydrochloric acid, so if you don't want hydrochloric acid in your eyes, nose, lungs, don't breathe it!
Small amounts of table salt and baking soda in the cat will go unnoticed. The ideal method can be used if a source of compressed HCl gas is found. It is sold in lab cylinders by chem supply houses and is not watched by the DEA. Just stick on a regulator, affix the rubber hose with a glass extension for submersion in the solvent, and open the valve to expel the gas through the solvent to produce pure cat HCl.
Ephedrine is oxidized to produce methcathinone. The methcathinone is then converted to the free base for separation from the rest of the unwanted crap mixed with it. The free base dissolves in toluene and not in water whereas the unwanted crap dissolves in water and not in toluene. Since water and toluene separate into 2 layers the toluene layer containing the cat free base is saved and the water layer thrown out. The toluene could probably be evaporated leaving crystals of cat free base which could probably be smoked but I haven't heard of anyone smoking it nor have I heard of its effects on the human body. The cat free base is converted to cat salt using dilute hydrochloric acid or anhydrous HCl gas. Cat salt is soluble in water and not in toluene, just the opposite of the free base. Using HCl gas the salt produced has no water layer to dissolve in so it crystalizes out. Using dilute HCl the salt leaves the toluene layer as before but has a water layer (the water diluting the HCl) to dissolve in. This water layer is saved and the water evaporated, leaving methcathinone-HCl.
Source: Posted by Psychokitty on The Hive, July 17, 2004
Many bees have reported interesting and strange details to the patent literature, both new and old.
In regards to inventions of mechanical or industrial processes, such as a new method for eliminating pollution from contaminated sites, such examples of the patent literature fall a bit short of detail. This may occur for any number of reasons, the most typical ones perhaps surrounding the necessity of providing limited information about the process, construction, and overall function of the invention itself. My guess is that the vagueness in detail of many current inventions is for the purpose of securing the potential profits said invention may yield through it's application in the global market.
But patents detailing standard chemical processes, such as a new reaction protocol for synthesizing any one of many commercial reagents or substances, typically seem to be quite accurate in that they appear to have only a marginal promise of profitability, and seem more an extension of the inventor's desire to report and promote his/her/their most recent contribution to science. In short, these patents, both new and old, oftentimes are very detailed and, at least on the surface, appear to be accurate, and according to heresay, generally provide positive results.
However, patents detailing potentially "controversial" inventions - that for any one of many reasons, political, scientific, ethical, or perhaps even those based on someone's desire to "hint" to possible future buffs of patent history that they, the researcher, author, transcriber, or sponsor of the patent, knew more about the particular invention in question and, equally importantly, about the manner in which it was published - seem to retain an air of mystery that perhaps the typical casual reader who tends to refrain from probing and asking questions, would miss.
My point is quite simple: Many patents (and scientific articles as well) that I have read have strangely been marred by errors which seem difficult to dismiss as simple oversights. Since the primary focus here at the Hive is to explore various aspects to the drug phenomena, I will cite just a few examples of particularly strange errors in the pharmaceutical and chemical patent literature, that, to the best of my memory, are inexcusable as common and so-called expected "mistakes".
The Parke-Davis U.S. Patent detailing the synthesis of l-methcathinone from l-ephedrine indicates an over-usage of sulfuric acid in the chromic acid oxidation phase. I believe the required decimal point that would have accurately indicated the correct volume/weight of sulfuric acid required to prepare the Jones Reagent, is missing. To the inexperienced experimentor, following the instructions in the patent to the letter/number would likely, as has unfortunately been reported here at the Hive numerous times, lead to an overly acidic reaction which would in turn would make the subsequent processing and purification steps difficult.
Also, it has been reported time and again, that the 4-6 hour length of time mandated in the experimental section of the patent will NOT be enough for the oxidation to reach completion. In other words, an excessive amount of starting material (l-ephedrine, in the case of both the British Patent and U.S. Patent) would be present in the final product in what would likely be in an unacceptably and potentially dangerous excess.
Furthermore, the danger of condensation of two methcathinone base molecules to form the pyrazine derivative is not even hinted at in any of the three patents. This, I suspect, is either because the pyrazine would naturally be expected to be removed by a skilled experimentor through common prudent purification steps accompanied by the appropriate use analytical devices to determine purity. In this light, it is possible that the authors of the patents did not care about--or possibly were not even aware of--the ramifications the pyrazine contaminant would have on the future problem of social methcathinone use/abuse in what is, and has been, and will likely continue to be for quite some time, a drug prohibitionist society. Either way, the authors of the U.S. Patent, at least--if so inclined, and if they were alive--could argue that the inconsistencies found in the final draft of their published patent were a result of their commitment to and respect for the former literature from which they obtained their information, and that, in their view, at least, the simplist explanation to the issue of misreporting, is that they--the reseachers from Parke-Davis--directly copied their information from the previously published British Patent, detailing the same reaction scheme in the same vague and inaccurate way.
The British Patent - again, if I remember correctly - is focused primarily on the chemisty and synthesis of l-methcathinone; the U.S. Patent, on the other hand, appears to actually be a report on l-methcathinone clinical trails with results of toxicity laboratory experiments performed on rats. Maybe the synthesis of l-methcathinone was published in the U.S. Patent just for the sake of maintaining an air of professionality, via, of course, the inclusion of a concise and detailed experimental section. For all we know, the U.S. Patent research staff may have gotten their samples of l-methcathinone straight from the British. Huh. But I doubt that very much.
Strangely enough, the authors of the British Patent got their information from, I believe, a German Patent detailing the synthesis of l-ephedrine from the chromic acid oxidation of d-pseudoephedrine, which was then subsequently reduced by sodium metal (I think) to the l-ephedrine. Basically, the patent is a synthesis of l-ephedrine from d-pseudoephedine. I've done the math, and the exact same proportions of reactants are used in the German patent as are used in the British and U.S. Patents. The only difference is that the German patent uses both a much larger scale of reactants and a standing - yes, STANDING not STIRRING - reaction of six or so days as the time interval required to complete the chromic acid oxidation. The yield was reported to be about 80% l-methcathinone, which actually represented the intermediate to the final l-ephedrine product, which was the main focus of the patent.
The British patent and the U.S. patent use stirring for a 4 to 6 hr period of time to complete the oxidation of l-ephedrine to l-methcathinone. Strangely enough AGAIN, no yields are reported.
According to the much more detailed process of chromic acid oxidation of both ephedrine and pseudoephedrine as reported in the 1994 volume of Journal of Chromatographic Science (J. of C.S.)--I'll get the actual paper later for more details--the chromic acid oxidation should proceed through stirring of the reaction matrix for--if I remember correctly--12 to 18 hrs. However, in the J. of C.S. report, seemingly more useful experimental details are offered that, at least on cursory inspection, appear to fill in the gaps and limitations of the three former examples cited in the patent literature. In point of fact, the suggested reaction time, the purifaction protocol whereby the toluene solution is gassed by anhydrous HCl, distilled off under vacuum until a small quantity of toluene and the solubilized methcathinone-HCl is left. Then, the solution is quenched with anhydrous ether and the precipitated product filtered and recrystallized with IPA/acetone. This report is quite detailed compared to that reported in the former literature. It unfortunately is devoid of the unquestionably beneficial step of adding a minimal quantity of IPA to reduce the excess chromic acid to the amphoteric chromium hydroxide. The completely uniform green or blue solution can then be basified to liberate the methcathinone free base, a step which will also simultaneously solubilize the chromium hydroxide formed. Unfortunately, in lieu of this step, the author of the J. of C.S. adheres to the classic method of basification which, at the completion of the reaction, causes the time and again reported--inconvenient, and tediously removed--insoluble chromium hydroxide to precipitate out as a water insoluble chromium amphoteric hydroxide sludge.
Unfortunately, this article too offers what appears to be an erroneous and likely problematic step wherein a ridiculously excessive amount of sulfuric acid is called for (not a typo like in the British and U.S. Patents; merely a modification--a bad one, in my opinion, that would most likely be scorned by the Hive community at large). Why such a modification was suggested is certainly a good question as the recommended sulfuric acid concentration seems to be so excessive as to perhaps account for about more than 50% of the aqueous solution. As a matter of speculation, perhaps the authors of the J. of C.S. article were actually promoting a very prudent technique that would allow the overall chromic acid oxidation scheme to work in an optimal manner. Although this could be the case, it certainly doesn't look that way.
I would suspect that--based on the current knowledge of the general chromic acid oxidation--the quantity of sulfuric acid called for in the J. of C.S. periodical is either an accidental or intentional mistake. Perhaps in the instances so far mentioned, the authors have been, or presently are, either sympathetic or hostile to the cause of drug experimentation and research; therefore it is logical to assume they possibly had the wisdom to foresee both positive and negative commercial applications of their research.
Or perhaps, even more interestingly, the authors of the publications in question reported their information in such a manner that would allow only those individuals who were both knowledgeable, skilled, and qualified to "read between the lines" and make the necessary inferences about the patents secrets, thus implying the need to take certain productive and intelligent steps based on the available evidence.
Another simple yet compelling theory is that the authors of such patents and scientific articles--then as well as today--are bound by some governmental type of limitations in terms of how the experimental segments of scientific papers (particularly those written about the subject of illicit or potentially future illicit substances) are to be reported. Such a model would obviously favor qualitative evidence as the primary focus of scientific research while quantitative evidence would either be marginalized or altogether absent.
And last but not least, maybe the inventors of said erroneous patents were (are) just lazy about dotting every "i" and crossing every "t", and simply didn't catch the typos. However, in all honesty, I find this last possible explanation hard to swallow as the typo in question had appeared more than once (as a reminder, in both the British and U.S. Patents). The recurrence of such a big mistake, which would obviously affect the outcome of just about any application to research of the information contained therein, would obviously, at the very least, cause time consuming and costly mistakes, and at most, cause harm to a potential experimentor wishing to reproduce the results of the patent's claims.
To me, the whole thing smakes of some undisclosed political or ethical agenda, dating back all the way to the earlier half of the twentieth century.
BTW, this is a little off the subject, but I thought it worth mentioning that the molar ratios of the dichromate oxidation used to convert l-ephedrine/d-pseudoephedrine to l-methcathinone are completely equimolar to each other in all three patents, meaning that just enough sulfuric acid is added to the sodium or potassium dichromate to make just enough chromic acid to oxidize the exact amount of ephedrine/pseudoephedrine in solution.
As for the stereochemical consistency of the dichromate oxidation of ephedrine/pseudoephedrine, it is correctly reported in the J. of C.S., but suspiciously incorrectly reported in the J. of Forensic Sciences article covering the subject of methcathinone also indicated to be known as "Jeff", "Mulka", and "Ephedrone". It would seem, therefore, that a 100% yield from this reaction would be out of the question, as much of the chromic acid oxidant is reported to consume much of the desired methcathinone product, accounting for the 20% excess of the ephedrine enatiomer starting material left over. But, on the good side, l-ephedrine (1R,2S) and d-pseudoephedrine (1S, 2S) DO both in fact yield, upon direct oxidation with any number of oxidants, the more potent levo isomer of methcathinone. Racemization can occur due to the enolizable carbonyl group, but harsh reaction conditions and/or strongly basic conditions would have to exist for this to occur. This is merely interesting as this property is very much akin to the reduction of ephedrine/pseudoephedrine to the stronger dextro isomer of methamphetamine, in that the enantiomers, ephedrine/pseudoephedrine, upon clean oxidation or reduction, yield only one isomeric product, namely the most potent one.
More interesting but possibly irrelevant and off-topic information for the Hive masses:
Accidental application of excess sulfuric acid in dichromate aminoalcohol oxidations to aminoketones and the subsequent attempt to remedy the situation by basifying a bit to compensate for said excess, and then extending the length of the reaction to twice the amount indicated to compensate for the excessive volume of liquid in the reaction matrix, has been reported to lead to low yields and difficulty in reducing, at the end of the reaction, the excess chromic acid in solution with the standard application of a minimal quantity of 2-propanol (IPA). Surprisingly, and symptomatic of this particular problem, is that the solution does not change its appearance in color to that of the expected opaque green or opaque blue in the expected amount of time (2-3 minutes). Furthermore, the subsequent basification step is rendered difficult due to the formation of solids, most likely the typical insoluble chromium hydroxide salts that normally accompany the classic basification method to the aminoketone base liberation/isolation step essential to this and pretty much any other general alkylamino/aminoketone synthesis.
The above mentioned problem is reported to normally be avoided by the simple use of the appropriate ratio of reagents to that of the substrate (everything appears to be equimolar, according to former calculations). Also, the exact amount of sodium hydroxide required to effect basification (the details of which are absent in all of the patents) falls somewhere--again, according to previous reports--to a dramatically lesser degree than has been both assumed and even reported by members here at the Hive. I believe I read somewhere that the proper amount of base--for both the British and U.S. Patent basification step--is somwhere around 2.1 g of sodium hydroxide in enough water to form a 20% solution. This amount--I'm going by memory as I read these figures a long time ago--is necessary for either every 1 g of sodium or potassium dichromate or for every 1 g of aminoalcohol-HCl used in the oxidation reaction. I don't remember which. More research in this area is obviously called for.
I obviously got sidetracked from the main topic of this thread, but I do have other striking examples of perculiar errors in the patent literature and a host of wild theories as to why they made it to final publication. But I'm tired of typing, so that part of my report will have to wait for now.
Until sometime in the near future, use your time wisely and respond to my post. And, of course, take care!
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