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	All 19 posts		Subject: 1-(5-Indanyl)-2-methylaminopropan-1-one		Please login to post		Down

		starlight (Hive Bee) 04-30-03 10:33 No 430376				1-(5-Indanyl)-2-methylaminopropan-1-one (Rated as: excellent)
						Preparation and bioassay of 1-(5-Indanyl)-2-methylaminopropan-1-one hydrochloride 1-(5-Indanyl)-propan-1-one 73g aluminium chloride 300mL dichloromethane 46mL propionyl chloride 59g indane 600mL iced water 400mL 5% NaOH solution 100ml brine magnesium sulfate 59g (500mmol) indane was added over 45 minutes to a solution of 73g (550mmol) anhydrous aluminium chloride and 49g (525mmol) propionyl chloride in 200ml dichloromethane cooled via an external ice bath. The solution was allowed to stir for a further 2 hours at 20oC, and was then slowly added to 500mL stirred iced water. The lower dichloromethane layer was separated off, and the aqueous layer extracted with 2x50mL dichloromethane. The combined extracts were washed with 4x100mL 5% NaOH, 100ml water, 100ml brine and then dried over magnesium sulfate. The solvent was removed, and the ketone vacuum distilled at 96-98oC, to give 1-(5-Indanyl)-propan-1-one as a colourless oil. Yield: 75.0g (86%) 1-(5-Indanyl)-propan-1-one to 1-(5-Indanyl)-2-bromo-propan-1-one 75g 1-(5-Indanyl)-propan-1-one 2mL 48% HBr 24mL bromine 230mL glacial acetic acid 800mL water 500ml diethyl ether magnesium sulfate To a solution of 75g (430 mmol) 1-(5-Indanyl)-propan-1-one in 230mL glacial acetic acid was added 2mL 48% HBr followed by, over the course of an hour, 24mL (475mmol) elemental bromine. The reaction mixture, changed to an orange-brown color during the addition and was stirred for a further 1.5 hours. It was then then poured in small portions into 800mL ice-cold water, with swirling after each addition. The product separated as a green oil. The aqueous and product layers were poured into a separatory funnel, the green oil settling to the bottom. The stopcock was opened to tap off the product, and this led to crystallization of the product in the sep. funnel. Obviously the product should have been extracted with dichloromethane or similar, and then the solvent removed. Given that the product was lime-green, it was decided that it should be recrystallized from ether. The next 2.5 hours was spent removing the product from the separatory funnel with warm ether. The ether was then reduced by means of rotovap, and the product allowed to crystallize. The ether solution was decanted, reduced and crystallized two more times to yield 90g of 1-(5-Indanyl)-2-bromo-propan-1-one as sparkling off-white crystals with very slight green tinge when viewed under some lighting conditions. Yield: 90g (83%) This could be improved by following a more sensible workup!! 1-(5-Indanyl)-2-bromo-propan-1-one to 1-(5-Indanyl)-2-methylaminopropan-1-one hydrochloride 13.5g methylamine HCl in 15mL water 7.9g sodium hydroxide in 20mL water 12.5g 1-(5-Indanyl)-2-bromo-propan-1-one 30ml 5% HCl 135mL toluene 225mL water acetone absolute ethanol To a stirred solution of 12.5g (50mmol) 1-(5-Indanyl)-2-bromo-propan-1-one in 45mL toluene held at 15oC by water bath was added, over 5 minutes, 6.2g methylamine in 35mL water (prepared by adding a chilled solution of 7.9g (198mmol) sodium hydroxide in 20mL water to a cold solution of 13.5g methylamine HCl in 15mL water). The mixture was allowed to stir for a further 16 hours at 10-12oC, during which time the toluene layer took on a pink color, and was then was poured into 150mL ice-cold water. The toluene layer was separated off, and the remaining freebase extracted with 2x20mL toluene. The combined toluene extracts were washed with 3x25mL water, and then acidified with 2x15mL dilute HCl. The combined acidic extracts (which were bright yellow in colour due to pyrazine contamination were then washed twice with 25mL toluene and evaporated under vacuum to dryness, allowing an off-white solid to form. This solid was recrystallized from absolute ethanol/acetone to yield 5g of fluffy, snow-white crystals. Yield: 5g (49%) This will probably be improved through reduction of the recrystallization solvent and further crystallization Bioassay: Insufflation is not a nice route for this product. It is so fine, it ends up in your lungs and is pretty irritating to the mucus membranes of the nose too. Nevertheless, it was progressed in the interests of science. At first, ~10mg was snorted with no effect. After half an hour, a further 10mg was tried with no effects. After a further hour, 20mg was snorted. The effects were like borderline stimulant with no psychedelic or empathogenic qualities. The duration of effect was maybe 45min. A further 20mg an hour later produced a similar response. No more doses were taken and the time was 12.30am. Sleep was easy at 1.30am when it was attempted. Waking at 6am was earlier than expected, but feel good this morning. Further bioassays at higher doses through an oral route are currently being progressed as this is typed. 125mg has been ingested on an empty stomach in two portions separated by 45min today. No detectable effects as yet (1hr 5min after first dose). This compound is not very active. Asides: Maybe I will try to substitute the bromine with ammonia rather than methylamine. That may help. Can anyone advise if I could follow the same experimental procedure replacing methylamine HCl with ammonium chloride? Thanks: Thanks to Kinetic for posting a good writeup structure that I copied, as it saved me quite a bit of thinking. Pathetic excuses: Sorry if my compound naming is a bit off, I have not learnt to do the nomenculature properly yet.
		starlight (Hive Bee) 04-30-03 11:37 No 430389				update
						230mg consumed orally over the course of 2.5 hours. very slight stimulation, loss of appetite. no other discernable effects. EDIT: being somewhat of a fool I just decided to snort another 150mg (T+3hrs). Again, stimulant effects only discernable. Nose and back of throat hurt substantially.[ To my disappointment, I think that this compound can be classified as crap. Ah, maybe i spoke too soon i'm feeling pretty good now. Still, this compound is a bit weak for my liking and seems only to be active on insufflation which is painful. another 125mg was snorted 15 minutes after the last 150mg. Mucus membranes of the nose are now inflamed enough to prevent any further administration of the material. Effects have increased but are still nothing to write home about
		Kinetic (Hive Bee) 04-30-03 12:43 No 430399				Oh
						That is a shame! I don't really know what to say about the lack of effects, which I think could be the same for the 4-methy substituted cathinone if it was eaten rather than insufflated. I didn't try any method other than insufflation of 4-MMC. I could suggest that if you were to give it one last try, wait a few days and insufflate 100mg, purley in the name of science of course. I have a feeling that replacing methylamine with ammonia will seriously affect the yield, and you could quite easily end up with nothing. Another way which may work on the bromoketone is a Delepine reaction; alpha-bromoketones are far more activated than iodoalkanes, so this may 'cancel out' the usual steric hindrance when performing Delepine reactions on secondary halides. I have some references for this on alpha-bromoacetophenone giving yields of 80% or so, so maybe they could be adapted. The nomenclature is right all the way through, to the best of my (quite limited) knowledge. It's just a shame the product was a disappointment. Still, it's great to see writeups of new compounds. If Shulgin had given up at his first disappointing compound, there would be a huge amount missing from PIHKAL, probably all of Part two I suspect. I had an idea a couple of days ago about this very compound, and it's stability to a HI/red phosphorus reduction. I can't see any problem with this type of reduction on an alkyl substituted ring, so if you happened to have any reagents lying around which could reduce a benzylic ketone to an alkane (either via one or two steps), you'd end up with the N-methyl analogue of IAP: https://www.rhodium.ws/chemistry/iap.html. I was wondering if the HI/red phosphorus reduction could be done in one step from the ketone; it's certainly possible to reduce some benzylic ketones directly to alkanes this way, so it's something which may be interesting. See Post 429497 (WizardX: "Mr_Wrath: The GAA serves as a solvent for...", Stimulants) for a couple of related examles. Keep up the good work, and please don't be too demoralised about this. Edit: Comment on your edit! Excellent! I think that was a very foolish but completely necessary thing to try! The alkyl substituted methcathinones seem to be rather weak I agree, but still quite fun. Hopefully the lack of insomnia will also carry through to this compound (what are you going to call it, IAMC?), something you'll be grateful for tonight. Relatively large doses seem to be necessary, but I can cope with that in the name of research. I found that when insufflating other alkyl cathinone analogues, a little bit up each nostril first, then the rest over a couple of minutes makes the pain more bearable. Or, you could take it every day until you're used to the pain. I recommend the first option, at least at first.
		Barium (Hive Addict) 04-30-03 15:05 No 430413				Great work
						Great work, but sad outcome. The information is, however, very useful. Freaky
		Antoncho (Official Hive Translator) 04-30-03 17:28 No 430433				Some notes and questions.
						First of all, - Bravo, StarLight! That was a fine job! I am impressed, to say the least! 2nd - ever considered injecting this stuff i/v? 'Course, it has to bee very very pure (like rextallized once again) and the injection has to bee done very carefully (read VERY SLOWLY), but that might prove actually worthwhile as well as sighnificantly less painful. Don't worry, as long as the solution is absolutely aseptic and entirely free from insoluble inpurities, i/v'ing is actually more safe than via intranasal route. 3rd - am i correct to assume that Clemmensen reduction is compatible with aminogroups? If so, than refluxing it in Zn/HCl should bee a nice and straightforward alternative to HI/P reduction! And 4th - what lead you to believe that you'd gotten the right (4,5-trimethylene) isomer? Any refs? I mean, electrophylic substitution of indane ring seems to bee unselective in its nature (see , e.g., Post 411005 (Promethium: "4- and 5-Indanaldehyde", Novel Discourse)) - and the corresponding 2,3-trimethylene-metamphetamine is quite certain to bee inactive (at least 2,3-dimethyl-amph is, see Patent GB573120) Not intending to rain on your parade, just for the purpose to clear the subject entirely... Yours sincerely, Antoncho
		starlight (Hive Bee) 05-01-03 15:43 No 430609				this stuff is dogpoo
						Next day and my nose has finally cleared of horrid thick mucus. This compound is *terrible* on your mucus membranes. Large amount of diarreah this morning too. Maybe this stuff is a bit toxic. Effects were really short lasting and less good than almost anything else tested to date (and i've tried some pretty crappy drugs). As for i/v'ing -- sounds fine in principle, in practice i don't like the idea (no rational reason I'm afraid). Clemmensen: I would have thought that this is compatible with amino groups, but I don't want to use mercury. Also not keen on hydrazine before anyone suggests Wolff-Kishner. As to positional isomers: I'm afraid it is naivity that led me to believe that I have the right positional isomer. You have pointed out something very interesting there. Still I would expect that I got at least a misture of 4- and 5- Indanyl isomers, with more of the 5. What do you think? Lastly, anyone got any ideas on removing the carbonyl group without highly toxic reagents?
		moo (Hive Bee) 05-01-03 20:46 No 430668				Modified clemmensen
						I think Antoncho is referring to this with Zn/HCl clemmensen reduction: http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0289.  No mercury needed.
		starlight (Hive Bee) 05-02-03 09:56 No 430797				Clemmensen / modified clemmensen
						Having looked at this a bit further: 1. Traditional Clemmensen is unlikely to work well on cathinones, as they are too likely to produce pyrazines under these conditions. 2. Modified Clemmensen: Not sure about this. Maybe the temperature is low enough to make pyrazine formation less of an issue, but the substrate will be in the form of an HCl salt with all that acid around. That's going to make it pretty insoluble in the ether, which may cause problems here don't you think? Perhaps it would be possible to reduce the ketone to an alcohol with borohydride? The alcohol could then be converted to the alkane by H3PO4 EDIT: H3PO3, thanks Kinetic
		Kinetic (Hive Bee) 05-02-03 14:17 No 430846				Pyrazines
						I had feared the same on any direct reduction from cathinones to amphetamines, until I read that salts of cathinones are far more stable to heat than the freebase; the complete lack of basicity of the protonated nitrogen will stop the formation of pyrazines. This might be interesting because both the HI/red phosphorus and the Clemmensen are carried out under strongly acidic conditions, so the amine will be 'protected' as such. We know amines are stable under reflux with HI at least. The ketone to alcohol via borohydride should work, and may be your best bet if you don't want to try HI/red phosphorus and if the modified Clemmensen proves unworkable. I don't know the first thing about stimulant chemistry, but the current reducing agent everyone seems to be talking about (I hope I got this right..) is phosphorus acid, H3PO3. If this can reduce alcohols to alkanes, maybe it can also reduce ketones to alkanes thus avoiding the borohydride step, and being rather environmentally friendly in the process. What a nice combination.
		Rhodium (Chief Bee) 05-02-03 18:43 No 430897				Article w/ physical data on some indans
						1-Hydroxy-1-(5-hydrindenyl)-2-aminoalkanes Pfleger, Robert; Rauer, Kurt.    Chem. Ber. 90, 1500-12 (1957).  CA 54, 44540 (1960) Abstract Some hydrindene compds. similar to adrenaline and ephedrine were prepd. (Throughout this abstr. R = 5-hydrindenyl.)  Hydrindene (I) (dried over CaCl2) (48 g.), 51 g. CH2ClCOCl, and 320 cc. dry CS2 treated during 45 min. with 60 g. finely powd. AlCl3 with ice cooling, the mixt. allowed to stand 0.25 hr. in the cold, refluxed 4 hrs. (moisture exclusion), cooled, poured into 400 cc. concd. H2SO4 and ice, the CS2 phase washed with 15% HCl, aq. Na2CO3, and H2O, dried, evapd., the residue distd. in vacuo (b11 171°), and the product recrystd. from 600 cc. petr. ether gave 64 g. RCOCH2Cl (II), m. 60.5°, corrosive to the skin; 86% oxime, m. 104°; with PhNH2, RCOCH2NHPh, m. 74.5°.  Similarly, 48 g. I and 95 g. MeCHBrCOBr gave 81 g. RCOCHBrMe (III), b10 175°, m. 74.5° (100 cc. EtOH or iso-PrOH).  HONH2.HCl (4.6 g.) and 3.4 g. Na2CO3 in 20 cc. H2O added to 4 g. III in 60 cc. warm MeOH, the mixt. refluxed 10 hrs., treated with 100 cc. warm H2O, and the ppt. crystd. from 15 cc. 80% EtOH gave 0.5 g. RC(:NOH)C(:NOH)Me, m. 222-3° (decompn.) (80% EtOH).  III (3 g.), 30 cc. EtOH, and 1.5 g. PhNH2 refluxed 1 hr., the soln. concd. to 15 cc., and cooled gave 1.4 g. RCOCHMeNHPh, m. 94°; HCl salt decompd. 211.5-12.0°.  II or III (2 g.) added to 10 g. NaOH and 1 cc. Br in 70 cc. H2O, allowed to stand 3 hrs. with occasional shaking (or 20 hrs. with frequent shaking), filtered, and the filtrate acidified with dil. H2SO4 contg. sulfite gave RCO2H, m. 183° (C6H6).  II (25 g.) cooled in an ice-salt mixt. allowed to stand 1 hr. (not longer) with 70 cc. 17% MeNH2-dioxane with occasional shaking, poured into finely crushed ice and 300 cc. satd. aq. Na2CO3, the base extd. with Et2O, the ext. dried over K2CO3 with ice cooling, evapd. in vacuo at 20° (bath temp.), and the base again treated with dry Et2O and evapd. in vacuo at 20° gave RCOCH2NHMe, unstable (the isolation of the base should be made within 1.5 hrs.); HCl salt (IV) m. 219-20° (decompn.).  Similarly, 25 g. III treated 2 hrs. under ice cooling with 17% MeNH2-dioxane (or at room temp. with 33% aq. or 40% alc. MeNH2) gave 16 g. RCOCHMeNHMe, b9 165°, unstable oil; HCl salt (V) m. 215-16°.  II (20 g.) added to 28 cc. Et2NH in 15 cc. Et2O with ice cooling, allowed to stand 12 hrs. at room temp. with occasional shaking, filtered, the Et2O filtrate washed with aq. Na2CO3 and H2O, dried, evapd., and the residue immediately distd. in vacuo gave 17.5 g. RCOCH2NEt2 (VI), b15 187°, unstable oil; HCl salt (VII) m. 147.5-8.5°; VI was also obtained with 60% aq. Et2NH at 0°.  Anhyd. (CO2H)2 (6 g.) and several drops AcCH2CO2Et added to 10 g. VI in 6 cc. warm abs. EtOH, cooled, treated with Et2O, and the product crystd. from EtOH-Et2O gave 11.5 g. VI acid oxalate, m. 124.5-5.5°, very stable.  Similarly, 25 g. III, 35 cc. Et2NH, and 19 cc. Et2O after 2 days at room temp. gave 20 g. RCOCHMeNEt2, b15 187°, unstable oil; HCl salt (VIII), m. 170-1.5°, hygroscopic.  IV (10 g.) in 80 cc. MeOH hydrogenated with 0.15 g. PdCl2 at room temp. and atm. pressure, after absorption of the calcd. amt. of H shaken 2 hrs. more, filtered, the filtrate evapd., the residue ground with dry Me2CO, kept in vacuo at 100°, dissolved in 15 cc. warm iso-PrOH, and pptd. with 30 cc. warm dry, Me2CO gave 8.2 RCH(OH)CH2NHMe (IX) HCl salt (X) m. 124-5.5°.  X (10 g.) in 50 cc. H2O treated with excess aq. Na2CO3 and the product dissolved in 50 cc. warm C6H6 and pptd. with 10 cc. warm petr. ether gave 7.1 g. IX, b13 177°, m. 132-2.5°.  IX (1 g.) added to 3 g. p-O2NC6H4COCl (XI), 20 cc. dry C6H6, and 6 cc. dry C5H5N under ice cooling, after 15 min. the mixt. boiled 1.5 hrs., cooled, dild. with 40 cc. (CH2Cl)2, shaken with 70 cc. 1.5N HCl, 2N NaOH, and H2O, the org. layer dried, evapd. in vacuo, and the residue recrystd. from AcOH gave 2.1 g. O,N-bis(p-nitrobenzoyl) deriv. of IX, m. 167°.  V (12 g.) in 90 cc. MeOH hydrogenated as above gave 10.2 g. erythro-RCH(OH)CHMeNHMe (XII) HCl salt (XIII), m. 208-9° (35 cc. EtOH, 10 cc. EtOH, 10 cc. MeOH, 30 cc. Me2CO).  XIII (8 g.) in H2O treated with 20 cc. 25% warm aq. NaOH and the product recrystd. from 50 cc. C6H6 gave 6.2 g. erythro-XII, b8 171°, m. 113°; O,N-bis(p-nitrobenzoyl) deriv. m. 182-3° (EtOH), preliminarily purified by soln. in 8 cc. warm AcOH and pptn. with 16 cc. warm MeOH.  VII (15 g.) in 45 cc. MeOH hydrogenated as above gave 12 g. RCH(OH)CH2NEt2 (XIV) HCl salt (XV), m. 124-6°(dry Me2CO), hygroscopic.  XV (10 g.) gave 7 g. XIV, b15 187°, stable oil; 79% O-Bz deriv. of XIV HCl salt, m. 166° (dry Me2CO), by a Schotten-Baumann reaction of 4.3 g. XIV or 5 g. XV with 70 cc. 2N NaOH and 5 g. BzCl.  VIII (20 g.) in 45 cc. MeOH hydrogenated as above gave 16.5 g. RCH(OH)CHMeNEt2(XVI) HCl salt (XVII), m. 185-6° (iso-PrOH-3 vols. Me2CO).  XVII (10 g.) was converted to 7.5 g. XVI, b15 188°, stable oil; O-Bz deriv. of XVI, HCl salt m. 162-4°.  II (30 g.) in 120 cc. HCONMe2 stirred 2 hrs. with 33 g. C6H4(CO)2NK, mixed with 240 cc. CHCl3 and 600 cc. H2O, the mixt. shaken vigorously, the aq. phase extd. with 2 ´ 60 cc. CHCl3, the combined CHCl3 soln. washed with 300 cc. 0.3N NaOH and 300 cc. H2O, dried, evapd., the residue boiled with 100 cc. Et2O, and the ppt. filtered off gave 38 g. RCOCH2N(CO)2C6H4-o (XVIII). m. 175-5.5°.  III (30 g.) treated similarly, the residue dissolved in 19 cc. warm AcOH, the soln. cooled, and when crystn. began treated with 38 cc. 1:1 Et2O-petr. ether gave 27 g. RCOCHMeN(CO)2C6H4-o (XIX), m. 99.5-100.0° (EtOH).  Finely powd. XVIII (5 g.) heated 10-15 min. with 35 cc. 10% aq. KOH, the soln. mixed with 15 cc. warm H2O, treated immediately with excess 10% cold aq. HCl, cooled, the product collected, ground with H2O, dried in vacuo overnight, and boiled with 40 cc. EtOAc gave (as EtOAc-insol.) 4.3 g. RCOCHR'NHCOC6-H4CO2H-0 (XX) (R' = H) (XXI), m. 168.5° (decompn.).  XIX (5 g.) treated as above, the soln. cooled before adding HCl, and the crude product boiled with 25 cc. EtOAc gave (as EtOAc-insol.) 4.8 g. XX (R' = Me), m. 184-5° (decompn.) (Me2CO).  XXI (from 25 g. XVIII) ground with H2O, moist XXI boiled 2 hrs. with 250 cc. 20% HCl, cooled, filtered, the filtrate evapd. to dryness in vacuo at 50-70°, the residue dissolved in 20 cc. warm MeOH, the soln. mixed with 50 cc. warm Me2CO, treated with C, filtered, and the filtrate allowed to cool (addnl. product from the mother liquor) gave 12.3 g. RCOCH2NH2 (XXII) HCl salt (XXIII), m. 194° (EtOH-Et2O).  Direct sapon. of 1.5 g. XVIII with 4.5 cc. concd. HCl and 4.5 cc. AcOH gave only 48% XXIII, m. 191°.  XIX (25 g.) treated as above, the pptd. o-C6H4(CO2H)2 recrystd. from H2O, the mother liquor combined with the aq. acid filtrate, evapd. to dryness as above, the residue evapd. in vacuo with MeOH, and recrystd. from 800 cc. iso-PrOH gave 15 g. RCOCHMeNH2 (XXIV) HCl salt (XXV), m. 236° (decompn.) (EtOH-Me2CO).  Treating III with 18% alc. NH3 (excluding air) followed by boiling 2 hrs. with 20% HCl gave only 12% XXV.  Finely powd. XVIII (25 g.) refluxed 17 hrs. with 50 cc. 48% aq. HBr and 50 cc. AcOH, cooled, filtered, the filtrate evapd. in vacuo at 50-70°, and the residue dissolved in 10 cc. MeOH and the soln. treated with 30 cc. Me2CO gave 18.9 g. XXII.HBr, m. 192.5° (EtOH-Et2O).  XIX (25 g.) treated similarly, the residue dissolved in the exactly required amt. iso-PrOH, and the soln. concd. to half its vol. gave 18.4 g. XXIV.HBr, m. 230° (decompn.) (EtOH-Et2O).  XXIII (14 g.) in 150 cc. MeOH catalytically hydrogenated as above (H absorption rather slow and required renewal of catalyst several times) and the product recrystd. from 400 cc. iso-PrOH gave 11.4 g. RCH(OH)CH2NH2 (XXVI) HCl salt (XXVII), m. 215° (decompn.) (sinters from 170°).  XXVII (5 g.) was converted into 3.1 g. XXVI, m. 130° (decompn.); O,N-bis(p-nitrobenzoyl) deriv. m. 166°.  Similar redn. of 12 g. XXV in 120 cc. MeOH gave 10.5 g. RCH(OH) CHMeNH2 (XXVIII) HCl salt, m. 181.5-2.0° (EtOH-Me2CO), converted to 76% XXVIII, m. 132.,5-3.0° (C6H6);  O,N-bis(p-nitrobenzoyl) deriv. of XXVIII, m. 160.5-1.0°.  XV (15 g.) added during 10-15 min. to 25 cc. SOCl2 and 25 cc. dry CHCl3 under ice cooling, allowed to stand 3.5 hrs. (excluding moisture), evapd. to dryness in vacuo at 35°, the residue dissolved in CHCl3, the soln. evapd. to dryness, this procedure repeated with dry Me2CO, and then pptd. from Me2CO soln. with Et2O gave 10.5 g. RCHClCH2NEt2.  HCl (XXIX), m. 128°.  XV (2 g.) added to 5 cc. dry CHCl3 and 3 g. PCl5 under ice cooling, allowed to react 2.5 hrs. at room temp. (excluding moisture), treated dropwise with 3 cc. abs. EtOH, evapd. in vacuo at 45°, and the residue treated as above gave 1.13 g. XXIX.  XXIX (0.5 g.) in 10 cc. H2O heated 1 hr. on a boiling H2O bath with 10 cc. satd. aq. Na2CO3, cooled, extd. with Et2O, the ext. dried, and treated with dry HCl gave 0.3 g. XV, m.p. and mixed m.p. 123-4° (dry Me2CO).  XXIX (4 g.) in 40 cc. MeOH catalytically hydrogenated as above and the product recrystd. from 30 cc. dry Me2CO gave 3.2 g. RCH2CH2NEt2 (XXX) HCl salt, m. 157-7.5°, converted to 89% XXX, b14 158.5°.  XXIX (7.5 g.), 18 cc. Et2H, and 15 cc. abs. EtOH refluxed 8 hrs., cooled, treated with 200 cc. 10% aq. Na2CO3, extd. with Et2O, the ext. dried, and the  residue distd. gave 6.9 g. RCH(NEt2)CH2NEt2 b13 178-82°; di-HCl salt m. 204-5° (EtOH-Me2CO.sbd.Et2O), hygroscopic.  RAc (von Braun, et al., C.A. 14, 3659) (9 g.), 18 g. Zn-Hg, and 54 cc. 1:2 dil. HCl refluxed 5 hrs. (4.5 cc. concd. HCl added each hr.), the mixt. steam distd., the distillate extd. with Et2O, the ext. washed with aq. NaOH and H2O, dried, evapd. and the residue distd. gave 6.3 g. REt, b13 92°.  II reduced similarly gave 63% REt. IV (5 g.), 7..5 g. Zn-Hg, and 20 cc. concd. HCl refluxed 0.5 hr. gave 1.7 g. REt.  VII and XXIII reduced similarly gave 69% and 77%, resp., REt.  erythro-XIII (15 g.), 25 cc. SOCl2, and 25 cc. dry CHCl3 treated as above and the soln. dild. with 30 cc. dry Et2O gave 14.9 g. RCHClCHMeNHMe.HCl (XXXI), decompg. 214° (MeOH-Me2CO).  erythro-XIII (2 g.), 3 g. PCl5, and 10 cc. dry CHCl3 treated as above gave 0.9 g. XXXI, decompg. 208°.  threo-XIII (1 g.), 2 cc. SOCl2, and 2 cc. CHCl3 kept 1.5 hrs. and treated with 2 cc. Et2O gave 0.97 g. XXXI, decompg. 210°. XXXI (8 g.) in 80 cc. warm H2O and 16 g. KOH in 50 cc. H2O and 80 cc. MeOH refluxed 1 hr., mixed with 20 cc. H2O, cooled, and the ppt. recrystd. from 35% iso-PrOH gave 4.6 g. threo-XII, m. 104°.  XXXI (0.4 g.) in 10 cc. H2O and 1 g. AgNO3 in 10 cc. H2O heated 1.5 hrs. on a boiling H2O bath, aq. NH3 added to dissolve all AgCl, the mixt. cooled, and the ppt. filtered off gave 0.18 g. threo-XII; HCl salt m. 202-3°.  erythro-XII (1 g.) or 1.2 g. erythro-XIII, 40 cc. 1.5 N NaOH, and 12 cc. alc. free CHCl3, treated during 15 min. with 1 g. XI with vigorous shaking, allowed to stand 1.5 hrs. with occasional shaking, washed with H2O, dried, evapd. to dryness and the residue recrystd. from 25 cc. iso-PrOH gave 1.55 g. N-(p-nitrobenzoyl) deriv. (XXXII) of erythro-XII, m. 170°.  threo-XII similarly treated gave 85% N-(p-nitrobenzoyl) deriv. (XXXIII), m. 185° (iso-PrOH).  threo-O-(p-Nitrobenzoyl)-1-(5-hydrindenyl)-2-methylamino-1-propanol-HCl (XXXIV) (0.3 g.) dissolved in 30 cc. warm H2O, cooled, poured into 15 cc. 12% aq. NH3 with stirring, and the ppt. recrystd. from iso-PrOH gave 0.21 g. threo-XXXIII, m. 185°.  erythro-XXXII (0.3 g.) and 6 cc. concd. HCl heated 15 min. at 50°, evapd. to dryness in vacuo at 60°, the residue dissolved in dry Me2CO, the soln. evapd. in vacuo, and the residue crystd. from 5 cc. MeOH-5 cc. Et2O gave 0.28 g. threo-XXXIV, m. 207° (decompn.) (MeOH-Et2O). erythro-XXXII (0.4 g.) in 10 cc. warm dioxane treated 3.5 hrs. at 55° with dry HCl (excluding moisture), the soln. evapd. in vacuo, the residue treated with Me2CO, the soln. evapd. in vacuo, and the residue crystd. from 4 cc. MeOH-10 cc. Et2O gave 0.24 g. threo-XXXIV, m. 204° (decompn.).  threo-XXXIII similarly treated gave 0.32 g. threo-XXXIV, m. 204° (decompn.).  threo-XXXIII (0.3 g.) and 20 cc. concd. HCl heated 3 hrs. at 50°, cooled, filtered, the filtrate allowed to stand overnight, and the ppt. filtered off gave 0.1 g. crude threo-XXXIV, m. 185-90° (decompn.) (MeOH-Et2O).
		starlight (Hive Bee) 05-02-03 19:12 No 430907				thanks Rhodium
						I will do a mp. test some time over the next two weeks (got other things in progress at the moment so not sure exactly how soon, and then we can settle this once and for all hopefully (I assume you gave the data because you believe the different positional isomers will have significantly different melting points?)
		Rhodium (Chief Bee) 05-02-03 19:18 No 430910				Data
						Yes, exactly. I didn't find any data the 2,3-isomer when I searched, but there is no practical possibility that the mp of the amine hydrochloride as well as that of the bromoketone would coincide, so if both your values agree with the underlined ones in my post above, you can be sure of them being identical. If you conclude that your compound actually is the correct one, try to make the primary aminoketone from ammonia instead of methylamine, it should be more active (and comes with reccommendations from Assholium).
		cattleprodder (Hive Bee) 05-03-03 01:49 No 430997				My 6th cents.
						If you want to make an active, new ecstasy-like drug, then I would suggest making 3,4-dimethoxymethamphetamine from eugenol if you want to synth and bioassay something novel. The indans just don't seem to have it unless they are benzene methoxidized.
		GC_MS (Hive Addict) 05-03-03 08:23 No 431069				!
						If you want to make an active, new ecstasy-like drug, then I would suggest making 3,4-dimethoxymethamphetamine from eugenol if you want to synth and bioassay something novel. WOW! I think Shulgin never thought of that one! The faster you run, the quicker you die.
		cattleprodder (Hive Bee) 05-03-03 21:07 No 431170				Don't be an ass.
						Shulgin may have thought of it, but if you've carefully read Pihkal, you would know that he never tasted any.
		starlight (Hive Bee) 06-28-03 21:03 No 443160				some more info.
						still not done a mp. test as have been abroad. however, on return took some of the bromoketone and attempted to produce the aminopropanone. tried first with NH3 and just got a load of pyrazine. then did the delepine with the bromoketone in chloroform, filtered of the uronium salt, which was refluxed in ethanolic HCL. Ethanol was then evaporated. Ended up with some off-white powder which was washed with acetone till clean and white. hurt the nose, but not nearly as irritating as the methylamino product. 120mg had no effects upon insufflation. maybe we are dealing with the wrong positional isomer. what's wierd though is that all other reactions of indane like the acylation above, and the formlyation with dichlorodimethylether seem to attach mainly at the 5 position. Why would I have the wrong isomer? I will progress the mp. tests.
		Rhodium (Chief Bee) 06-28-03 21:42 No 443165				Varying isomer ratio in indane acylations
						The chloromethylation of indane produces a mixture of the 4- and 5-chloromethyl-indanes for example, and many other acylations/alkylations do too, with varying ratios between the two isomers (the ratio depending on a lot of factors).
		psychokitty («») 09-04-04 04:40 No 529515				I hope this helps . . .
						I have a few suggestions. In order to reduce the carbonyl function to the methylene group directly, I would either use Li in liquid ammonia or a combination of the cathinone salt, ammonium formate, and Pd/C catalyst in water, heated to reflux until the gas evolution ceases.  This suggested reduction is basically patterned after the one wherein O-acetyl-ephedrine is reduced to methamphetamine. This variation of the ammonium formate-Pd/C CTH reduction could include the use of those Pd BBs found in automotive catalytic converters.  One could just add the Pd BBs to the aqueous mixture of the cathinone/ammonium formate-Pd/C and reflux.  Since the roiling boil of the mixture should be enough to keep the reaction in motion, stirring wouldn't be needed and the continued evolution of gasses could serve as an effective visual aide to the progress of the reaction.  Just a thought. There are other alternative reducing agents.  Published in the literature is sodium borohydride's use in the methcathinone reduction to ephedrine.  I can post the experimental details if you're interested.  The HI reaction is likely the best one for reducing the indanyl ephedrine to the indanyl amphetamine.  HI has already been used to demethylate methoxy substituted amphetamines into their hydroxy ring-substituted counterparts safely.  Since the structure of such molecules is able to survive the rigorous conditions of the demethylation reaction and since the HI easily reduces ephedrine to methamphetamine, HI should work well at reducing indanyl ephedrine to indanyl amphetamine (I guess they should correctly be referred to as "trimethylene" ephedrine and amphetamine derivatives but I'm going to continue using the indanyl prefix just because it looks better). As for the application of the Delepine reaction in the synthesis of the indanyl cathinone derivative, from what I've read, it will not work.  Apparently, the reaction of hexamine and a-haloacetophenones goes to completion with the formation of the intermediate complex which can then be hydrolyzed in ethanolic HCl to yield the desired a-aminoacetophenone derivative.  However, according to an abstract (C.A.) that I have in my files, the Delepine reaction is not applicable to a-bromopropiophenone, which reacts with hexamine to form a complex that upon attempted hydrolysis, does not yield the expected a-aminopropiophenone.  Hexamine may react with substituted a-bromopropiophenones to form the desired complex in question.  I don't know.  But the available literature seems to suggest otherwise.  However, the Gabriel synthesis has successfully been applied to the a-aminopropiophenone synthesis utilizing the hydrazine hydrate hydrolysis of the complex formed from the reaction of a-bromopropiophenone and potassium phthalimide.  I'll soon post the experimental details to this reaction as well.
		starlight (Hive Bee) 09-29-04 09:41 No 533736				TFA or AlCl3 and NaBH4
						That carbonyl group could also be reduced by using Triflouroacetic acid/NaBH4 or by using AlCl3/NaBH4 in THF. Post 462116 (Rhodium: "NaBH4 Deoxygenation of Benzyl Ketones/Alcohols", Novel Discourse)

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Date: 05-19-24, Release: 1.6 (10-04-15), Links: static, unique