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skanic
(Newbee) 07-18-04 14:30 No 520071 |
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over oxidation | ||||||
In the synthesis described at :../rhodium /ephedro But it's a very strong oxidising agent and it's in the same proportions that ephedrine. Isn't it too much KMnO4 ? I had heard so much KMnO4 would tear in half the ephedrine molecule. speaks leaves, writes stays |
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WizardX (Wizard Master) 07-19-04 04:49 No 520178 |
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Oxidative Cleaverage | ||||||
Correct. Over oxidation will cleave the Ephedrone: 2-Methylamino-1-Phenylpropan-1-One at the benzylic C atom. The balanced equation is... 2 KMnO4 + 3 H2SO4 + 5 ephedrine ==> K2SO4 + 2 MnSO4 + 8 H2O + 5 Ephedrone OR 2/5 KMnO4 + 3/5 H2SO4 + 5/5 ephedrine (5/5 ephedrine = 1 mole of ephedrine.) |
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skanic (Newbee) 07-20-04 11:23 No 520394 |
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Then | ||||||
Then it means rhodium has to correct his page? |
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Rhodium (Chief Bee) 07-29-04 14:36 No 522455 |
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Note that the article is written by DEA chemists | ||||||
It means that the authors of the article I HTMLized did not optimize their procedure, and that is evident from their moderate 50% yield. I cannot change the information in a published article just because there are better ways to do something - at most I can add an inline comment. According to WizardX' calculations above, 1 mole of ephedrine is to be reacted with 0.40 moles KMnO4 to eliminate the risk of overoxidation, while the ratio actually used in the article is 0.78 moles of KMnO4 per mole of ephedrine. I'm not sure that his equation is directly applicable however, as it seems like they use HOAc instead of H2SO4 in the article, and that the reduced manganese species isn't Mn(II) (as in MnSO4), but rather Mn(IV) (in MnO2), making the balance different and the permanganate amount not as excessive. The Hive - Clandestine Chemists Without Borders |
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WizardX (Wizard Master) 07-31-04 06:26 No 522856 |
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Reagent Order | ||||||
Firstly, let me point out that ../rhodium /ephedro ../rhodium /ephedro 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 (2 g), and ephedrine hydrochloride (2 g). Notice the reagents used and the reagent sequence order. The MnO2 is being make before the ephedrine hydrochloride is being added, and the solvent is methylene chloride. My XFile 4 uses chloroform, with premade active MnO2 The balanced equation I posted is for both water/methylene chloride (or chloroform) solvents irrespective of the sequence of order the reagents are added. If you add ephedrine hydrochloride + potassium permanganate in water/methylene chloride, and then add H2SO4, NO over-oxidation will result if the correct balanced equation moles are used. If you use the mole amounts as stated in ../rhodium /ephedro Some more reading. http://www.orgsyn.org/orgsyn/prep.asp?pr http://www.orgsyn.org/orgsyn/prep.asp?pr |
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Rhodium (Chief Bee) 08-01-04 01:07 No 522985 |
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You aren't even using the same oxidant... | ||||||
Firstly, let me point out that ../rhodium /ephedro I disagree. The synthesis in ../rhodium /ephedro
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WizardX (Wizard Master) 08-03-04 05:28 No 523314 |
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Manganese Chemistry | ||||||
http://www.uncp.edu/home/mcclurem/ptable http://www.factmonster.com/ce6/sci/A0831 http://wwwchem.uwimona.edu.jm%3A1104/cou Redox properties of KMnO4. strong base MnO4- + e- -> MnO42- E=0.56V (RAPID) MnO42- + 2H2O + e- -> MnO2 + 4OH- E=0.60V (SLOW) moderate base MnO4- + 2H2O + 3e- -> MnO2 + 4OH- E=0.59V dil. H2SO4 MnO4- + 8H2O + 5e- -> Mn2+ + 4H2O E=1.51V
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psychokitty (« ![]() 08-03-04 08:35 No 523345 |
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A few questions, if you don't mind . . . | ||||||
Wizard X, In your write-up describing the oxidation of ephedrine using activated MnO2, you indicate that the heterogeneous oxidation can take place in anhydrous IPA (2-propanol) as well as other nonpolar solvents. Having researched the literature describing the use of activated MnO2 as an oxidant--specifically for the conversion of secondary alcohols to ketones--I must say that I am confused by your claims. Most reviews of the MnO2 oxidation state clearly that both primary and secondary alcohols--when applied to MnO2 heterogeneous oxidations--function poorly as solvents as they can be expected to deactivate a significant amount of the MnO2 available. So how is it that IPA can be used in this reaction to advantage? BTW, are the reported 70% yields expected by the activated MnO2 oxidation of ephedrine actually 30% unreacted ephedrine and 70% ephedrone or what? In other words, are there any byproducts from this reaction? Any left-over starting materials? Anything post-oxidation except the precipitated ephedrone-HCl? And is the stereoconfiguration of the resulting ephedrone-HCl levo, dextro, or the racemate? In case you didn't know, the activated MnO2 oxidation of ephedrine has already been documented in the literature. The details can be found in one of the citations listed at the end of the article referred to in Rhodium's following post: Post 502560 (Rhodium: "Methcathinone & Analogs: Synthesis & Analysis", Stimulants) The article's title has something to do with the degradation of (-)ephedrine in diethylether. If I remember correctly, the heterogeneous activated MnO2 (65 g) oxidation of of an anhydrous 100 mL diethylether solution of (-)ephedrine (10 g) takes place by stirring for about an hour or so to yield "a mixture of products" similar to the the two other oxidation reactions of (-)ephedrine detailed in the very same article (one, using supported silver carbonate; the other, lead peroxide [I think]). No yields are reported anywhere in the article. |
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WizardX (Wizard Master) 08-04-04 03:14 No 523501 |
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??? | ||||||
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psychokitty (« ![]() 08-07-04 18:58 No 524087 |
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Let's move on . . . (Rated as: good read) |
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I'm almost sure that the use of 2-propanol was listed as a potential solvent substitute in the reaction using the hydrochloride salt of ephedrine. I too have a copy of your XFile4 somewhere. I'll have to retrieve it later in order to verify or refute what I view as a minor discrepancy between the available literature and your write-up. But this issue over the use or misuse of 2-propanol is but a small quibble of mine. I'm more interested in the actual utility of your activated MnO2/ephedrone synthesis (for informational purposes, of course). I have thoroughly researched the literature for any available information that might offer credibility to your claim that this reaction actually works well in the way that you've reported that it does. As you no doubt already know--and again, assuming that I'm remembering things correctly--your XFile4 has no citations page. Had you made one available--including particularly that old article published about mid-century (wink) from which you took both your information AND experimental details--your synthesis using activated MnO2 as an efficient and mild benzylic primary and secondary alcohol oxidant might have gained more widespread attention and credibility here at the Hive a long time ago. Well, I have good news: Everything that I have read about this reaction indicates that it actually should work very well at facilitating the oxidation of just about any benzylic alcohol substrate in a more than facile manner and in high yield to the corresponding aldehyde or ketone. This means that, yes, both ephedrine and pseudoephedrine should be applicable to this reaction with both yielding--assuming that the reaction is as mild as has been reported--the more potent levo isomer of ephedrone. Being that the operational conditions are as simple as can be from something so ridiculously OTC, I'm surprised you haven't been more vigilant in the past about reporting this ephedrone synthesis. I'm actually giving you props here, Wizard X; congratulating you, if you will. Having made that clear, I wish you'd find time to answer some of my questions. Doing so would not only expand the understanding of this reaction that so far doesn't seem to have hit home with a lot of bees (or else we'd be hearing about it more) but it also would champion you as the first bee--moderator, no less--to offer up a synthesis of l-ephedrone (or, at the very least, d,l-ephedrone) in a high yield, quick and easy manner, using completely OTC items. More information, please. |
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WizardX (Wizard Master) 08-09-04 08:06 No 524376 |
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Another use for MnO2. | ||||||
Another use for MnO2. Tandem oxidation processes on activated alcohols using MnO2; Methyl esters http://www.syntheticpages.org/browse.php |
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psychokitty (« ![]() 08-30-04 09:04 No 528272 |
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YOU LIE!!! (or you need glasses, my friend) | ||||||
Here is the complete X-File that I long ago downloaded from your site: DISCLAIMER : THE FOLLOWING INFORMATION IS FOR INFORMATIONAL PURPOSES OR ACADEMIC STUDY ONLY. CHECK YOUR LOCAL, STATE AND FEDERAL LAWS, AND PROCURE THE NECESSARY PERMITS BEFORE UNDERTAKING ANY OF THE REACTIONS DESCRIBED BELOW. WIZARD X SHALL NOT BE HELD LIABLE AND INDEMNIFIED FROM IMPEACHMENT FOR THE USE, MISUSE, INJURY, DEATH, IMPRISIONMENT OR FELLATION DUE TO THE APPLICATION OF THIS INFORMATION. METHCATHINONE FROM MANGANESE(IV)DIOXIDE (MnO2) OXIDATION OF EPHEDRINE Ephedrine can be oxidizes to Methcathinone with manganese dioxide (MnO2) in anhydrous diethyl ether when freebase ephedrine is used, or anhydrous chloroform when ephedrine hydrochloride is used. C6H5-(CHOH)-CH(NHCH3)-CH3 + MnO2 ====>> C6H5-(CO)-CH(NHCH3)-CH3 + H2O + MnO The usefulness of this catalytic dehydrogenation reaction is it can convert hydroxy (-OH) groups to aldehydes or ketones for many compounds contaning a hydroxy (-OH) group on a benzylic or allylic position. The oxidation of allylic and benzylic alcohols of primary and secondary position using manganese(IV) dioxide is a heterogeneous reaction, and the detailed mechamism is unknown. The success depends on the freshness of the oxide and anhydrous conditions. With freshly prepared anhydrous oxide the yields may be high and the oxidation selective. It has been suggested that a possible mechanism may be : [ 1 ] R-CH2-OH + MnO2 ====>> R-CHO + H2O + MnO [ 2 ] H2O + MnO ====>> MnO2 + H2 but it is uncertain whether H2O is formed first or there is a straight H2 abstraction. Benzylic Position : C6H5-(CHOH)-CH(NHCH3)-CH3 + MnO2 ====>> C6H5-(CO)-CH(NHCH3)-CH3 + H2 + MnO2 C6H5-CH2-OH + MnO2 ====>> C6H5-CHO + H2 + MnO2 Allylic Position : C6H5-CH=CH-CH2-OH + MnO2 ====>> C6H5-CH=CH-CHO + H2 + MnO2 C6H5-CH2-CH(OH)-CH=CH2 + MnO2 =====>> C6H5-CH2-C(O)-CH=CH2 + H2 + MnO2 PREPARATION OF HIGH ACTIVITY MANGANESE(IV)DIOXIDE (MnO2) SOLUTION 1 : Make a solution of 223 grams (1 mole) of manganese(II)sulphate tetrahydrate (MnSO4.4H2O) or 169 grams (1 mole) of the manganese(II)sulphate monohydrate (MnSO4.H2O) in 300 mls of distilled water. SOLUTION 2 : 240 mls (2.5 mole) of a 40 % sodium hydroxide solution. A 40 % sodium hydroxide solution can be made by adding 400 grams of sodium hydroxide to 1 liter of distilled water. ADD SIMULTANEOUSLY during 1 hour, solutions 1 & 2, to a hot stirred solution of 190 grams (1.2 mole) of potassium permanganate (KMnO4) in 1200 mls of distilled water.[NOTE1] Continue stirring for another 1 hour. Isolate the dark brown to black MANGANESE(IV)DIOXIDE (MnO2) precipitate with filtration and wash thoroughly with water until the washing are colourless. Dry the product at 100 - 120 deg C and grind finely.[NOTE2] Dry again to ensure complete anhydrous manganese(II)dioxide. Store in an air tight container away from light. [NOTE1] Rinse the flasks of solutions 1 & 2 with a little distilled water into the potassium permanganate solution. [NOTE2] The wet manganese(II)dioxide precipitate can also be dried by azeotropic distillation in 25 gram portion with 150 mls of benzene. Suck the wet manganese(II)dioxide precipitate with good suction prior to azeotropic distillation. GENERAL PROCEDURE Dissolve 0.01 moles of ephedrine hydrochloride into 300 mls of anhydrous chloroform or 0.01 of ephedrine freebase into 300 mls of anhydrous diethyl ether in a 500 mls flask. Add 10 grams of manganese(II)dioxide, stopper and stir with sufficient speed, with a magnetic stirrer so that the manganese(II)dioxide is evenly distributed throughout the solvent. The solvent should become black with manganese(II)dioxide particles as the stirring vortex of the solvent keeps the manganese(II)dioxide suspended in solution. Stir for 2 hours at 25 deg C. Filter to remove the manganese(II)dioxide, rinse the flask and the manganese(II)dioxide on the filter paper with a little fresh solvent. The filtered manganese(II)dioxide can be re-activated by heating at 100 - 120 deg C. Evaporate the solvent off or better still, distil the solvent off so it can be recycled. [NOTE3] The yield is 60-75 % [NOTE3] If ephedrine hydrochloride is used with chloroform and the solvent is distilled off, then methcathinone hydrochloride is left in the distillation flask. If ephedrine freebase is used with diethyl ether and the solvent is distilled off, then methcathinone freebase is left in the distillation flask. The methcathinone freebase can be converted to the hydrochloride with dry HCl gas. SOLVENT TO USE EPHEDRINE HCl, C10H15NO.HCl molecular weight MW = 201.73 grams/mole EPHEDRINE FREEBASE, C10H15NO molecular weight MW = 165.23 grams/mole The freebase has a melting point 40 deg C with a ½ H2O. The boiling point is 225 deg C. If Ephedrine Hydrochloride is used then anhydrous chloroform or isopropyl alcohol is used. If Ephedrine Freebase is used then anhydrous diethyl ether, benzene or toluene is used. Notice the part about isopropyl alcohol in that second to last sentence! WizardX, you never answered any of my questions and I really find it very VERY hard to believe that you could have thoroughly scanned the entirety of your write-up and still missed the second to last sentence of it. ![]() Please, please, PLEASE answer the most recent questions I have for you concerning your write-up and/or explain the confusion over your recommended use of IPA as a solvent for the oxidation of ephedrine-HCl using activated MnO2. Thank you. ![]() |
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psychokitty (« ![]() 08-30-04 10:36 No 528285 |
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More oxidation reactions (Rated as: excellent) |
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Here is the relevant experimental section of J. Pharm. Pharmac., 1978, 30, 15-19 2-Methylamino-1-phenyl-propanone(III) (-)Ephedrine (1.0 g, 6.1 mmol) was refluxed in benzene (50 ml) with 'active silver carbonate' on Celite (10.1 g = to 18 m mol Ag2CO3) . . . in a Dean Stark apparatus until no more water was collected (60 min). The Celite/silver carbonate residues were filtered and washed, and the combined organic layers extracted with 2 M hydrochloric acid (2 * 20 ml). The acid layers were basified and extracted with ether (3 * 20 ml), the ether extracts dried (anhydrous MgSO4) and the basic components precipitated with HCl gas (0.46 g yield). The salt was recrystallized from ethanol-ether to give the title compound as an off-white solid (0.33 g, 33% yield), m.p. 170-178 deg C (with decomp.) (cf. Takamatsu, 1956, 173-175) Oxidation of (-)ephedrine base with nickel peroxide (-)Ephedrine base (0.03 g) was shaken for 15 min with nickel peroxide (0.01 g), in ether. The products were qualitatively examined by g.l.c. The product of oxidation of ephedrine base with nickel peroxide, gave peaks due to benzaldehyde (Rt 1.4 min) and the oxazolidones IIbi (Rt 7.6 min) and IIbii (a diastereoisomer of IIbi, Rt 9.9 min, 10% peak height of IIbi) on g.l.c. system 1. Oxidation of (-)ephedrine base with 'active silver carbonate' The product of oxidation of ephedrine with 'active silver carbonate' gave two peaks on g.l.c. (system 1 or 2); a sharp peak at 12.7 min, merging into a much broader peak centered at ca 15 min, which tailed extensively away from the solvent front towards the ephedrine peak. A small quantity of benzaldehyde and a negligible quantity of IIbi were also formed. A g.l.c.-ms run of the 12.7 min peak showed the base ion at m/e 58 with an m/e 56 ion increasing rapidly in intensity as subsequent scans were made, the m/e 58 ion rapidly decreasing in intensity. The main product isolated from the reaction was 2-methylamino-1-phenyl-1-propanone (III). See also the g.l.c. properties of III below, and under the synthesis. Oxidation of (-)ephedrine base with 'active manganese dioxide' (-)Ephedrine base (10.0 g, 61 mmol) was stirred in ether (100 ml) with 'active manganese dioxide' (65 g; prepared by Attenburrow, Cameron & others, 1952) at room temperature for 1 h. The manganese dioxide was removed by filtration, washed with ether and the residue discarded. The combined ethereal filtrates were examined qualitatively by g.l.c. and g.l.c.-ms. A mixture of products similar to those from both the above oxidations was obtained. So I have a question for anybee that can answer it: Can the yield of the above manganese dioxide oxidation of (-)ephedrine be determined through a qualitative g.l.c. and g.l.c.-ms scan of the ethereal filtrates? Here's some more useful information taken from A.J. Fatiadi, Synthesis, 65 (1976): . . . Another proceedure (ref 36) for active manganese dioxide involves the oxidation of acetone with potassium permanganate via internal cleaving of water. A filtered, saturated solution of potassium permanganate in acetone is kept at room temperature for 48-72 h. The resulting fine, somewhat bluish powder (<0.2mm) is filtered off, washed with aqueous acetone, and activated at 110-120 deg C for 16 h. Alternatively, finely ground potassium permanganate is refluxed with an excess of acetone until the pink color is discharged (3 to 4 h). The precipitate is filtered off, washed and dried at 110-120 deg C, or activated by azeotropic distillation of benzene (ref 37). . . . Ref 36: A.J. Fatiadi, unpublished results. Ref 37: I.M. Goldman, J. Org. Chem. 34, 1979 (1969). |
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WizardX (Wizard Master) 08-30-04 22:05 No 528426 |
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Yes, your right! | ||||||
psychokitty: Yes, your right! I missed the isopropyl alcohol when I quickly downloaded and browsed through it. I should have used the Find function in Notpad and searched for IPA and isopropyl alcohol. I recall I just browsed through the introduction through to the general procedure. Therefore, isopropyl alcohol (IPA) is incorrect and CAN NOT be used as a solvent. My sincere apology psychokitty! ![]() |
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WizardX (Wizard Master) 08-30-04 23:36 No 528443 |
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Chromatogram | ||||||
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