(Hive Bee)
04-05-03 00:31
No 423945
(Rated as: excellent)
Hi bees,
I've been bored over the last couple of days and had a few fun reagents lying around, so I though I'd try and make some 1-(4-methylphenyl)-2-methylaminopropanon
Preparation of 4-methylpropiophenone 1
73g aluminium chloride
300mL dichloroethane
46mL propionyl chloride
54mL toluene
600mL iced water
200mL 5% NaOH solution
Magnesium sulfate
54mL (500mmol, 46g) toluene was added over 30 minutes to a solution of 73g (550mmol) anhydrous aluminium chloride and 46mL (525mmol, 49g) propionyl chloride in 200ml dichloroethane cooled via an external ice bath. The solution was allowed to stir for a further 1.5 hours at 20oC, and was then carefully added to 500mL stirred iced water. The lower dichloroethane layer was separated off, and the aqueous layer extracted with 2x50mL dichloroethane. The combined extracts were washed with 2x100mL 5% NaOH, 100ml water, and then dried over magnesium sulfate. The solvent was removed, and the ketone vacuum distilled at 123-126oC, to give 1-(4-methylphenyl)-propan-1-one as a colourless oil.
Yield: 70.0g (95%)
Comments: Wash with 3x100mL 5% NaOH instead of 2x100mL.
DCM should be a better solvent, simply because it is easier to remove under vacuum.
4-methylpropiophenone to 2-bromo-4’-methylpropiophenone 1,2
38mL 4-methylpropiophenone
1mL 48% HBr
14mL bromine
125mL glacial acetic acid
650mL water
300mL dichloroethane
Magnesium sulfate
To a solution of 38mL (250mmol, 37g) 4-methylpropiphenone in 125mL glacial acetic acid was added 1mL 48% HBr followed by, over the course of an hour, 14mL (275mmol, 44g) elemental bromine. The reaction mixture, which changed to a nice pink colour during addition, was stirred for a further 1.5 hours, then slowly poured into 500mL ice-cold water, with swirling after each careful addition. The cream-coloured precipitated product was taken up in 200mL dichloroethane, and the aqueous layer extracted with 100mL dichloroethane. The combined extracts were washed with 2x250mL cold water, then dried over magnesium sulfate. The solvent was removed under vacuum, taking care to keep the temperature below 50oC, leaving a turquoise oil, 2-bromo-(4’-methylphenyl)-propan-1-one, which solidified almost immediately on cooling, into sparkling waxy crystals.
Yield: 57g (100%)
Comments: Try and keep the temperature below 30oC when removing the solvent – coloured crystals indicate some decomposition (above were a very light colour, so only mild). DCM would be a better extraction solvent since it could be stripped off at a lower temperature, causing less decomposition.
2-bromo-4’-methylpropiophenone to 1-(4-methylphenyl)-2-methylaminopropanon
13.5g methylamine HCl in 15mL water
7.9g sodium hydroxide in 20mL water
11.4g 2-bromo-4’-methylpropiophenone
6mL 37% HCl diluted with 24mL water
115mL toluene
225mL water
Acetone
To a stirred solution of 11.4g (50mmol) 2-bromo-4’-methylpropiophenone in 25mL toluene held at 20oC was added, over 5 minutes, 6.2g methylamine in 35mL water (prepared by adding a solution of 7.9g (198mmol) sodium hydroxide in 20mL cold water to a cooled solution of 13.5g methylamine HCl in 15mL water). The mixture was allowed to stir for a further 16 hours at 20-25oC, 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 then washed twice with 25mL toluene and evaporated under vacuum to dryness, allowing an off-white solid to form. 20mL acetone was added and was heated to boiling, forming a homogenous solution, which was then slowly cooled, allowing crystals to precipitate. The crystals were filtered and rinsed with around 100mL ice cold acetone.
Yield: 4.8g (45%)
Comments: Try stirring for 24 hours at 0oC, which will inhibit pyrazine formation. It may also lower the yield, but I'll see next time I try. It's doubtful (IMHO) that a yield of over 50% can be expected for this third step, because of the side reactions which can and do occur.
Yield given before recrystallisation, but after concentration and re-filtering and washing of the 100mL acetone washes, which provided a further 1g of product. Recrystallisation is highly recommended to remove any remaining pyrazine, and can be done from acetone/methanol.
1 Steps 1 and 2 both based on a synthesis of a Pyrovalerone analogue, 4-MPPH, Pyrovalerone with a hexane chain instead of pentane. Thanks to our endearing Nemo_Tenetur for providing the 4-MPPH synthesis
.2 The intermediate bromoketone is quite a powerful lachrymator, even when solid. Take care with washing your glassware after the synthesis, and please don't use hot water until you've thoroughly washed everything with cold water first.
3 Loosely based on Post 289410 (foxy2: "Methcathinone and ephedrine from propiophenone", Stimulants), although I never managed the 70-74% yields claimed when attempting this on bromobutyrophenone.
Of course this product could also be reduced in good yield to 4-methylephedrine, and then very easily made into (4-methyl)-methamphetamine. If you were to do that, I'd suggest reducing the bromoketone before adding the methylamine. This way, the methylamino group can be added under much more vigorous conditions, resulting in a higher yield. One attempt at this gave a yield of around 60%, but I'm sure it could be increased.
The bioassay went rather well too. I was a bit scared about what snorting 50mg might do, but since I've been almost constantly abusing the (badly synthesised) 1-phenyl-2-methylaminobutan-1-one (i.e. methcathinone with a butyl chain instead of the usual propyl), 50mg didn't do too much. I thought I'd wasted my time until I snorted another 100mg about 30 minutes later, and then it hit me. Intense rushes all over, lasting for well over 30 minutes. Since I have quite a high cathinone tolerance at the minute, I had another 100mg about an hour later, then 100mg an hour or so after that. Each time I could feel the rushes of energy coming across me, and after that, a fantastic sense of well-being that I haven't got from any drug before except my beloved ecstasy.
I'm still feeling the effects now, since I only completed the synthesis 6 hours ago, and began the bioassay an hour later
. It's a fun drug, and although less potent than methcathinone (unless my tolerance is really high), it's easy to make, and best of all, legal! Hopefully someone will find this of use, or at least of interest...
(Chief Bee)
04-05-03 01:16
No 423953
I'm impressed! You have not only tested a new drug, you have also synthesized it yourself completely from scratch and written a textbook example of what a synthetic writeup should look like!
I hope that the trend I have noticed here during the last few weeks will continue, there has been several people posting typed journal articles, notes on practical laboratory procedures & equipment as well as more than one really nice post compilation digest (Those digests feels like a sort of "Hive Abstracts" if you ask me).
(Hive Addict)
04-05-03 11:40
No 424045
Hat off for you Kinetic. Balls and brains, what a nice combination. If only you were a woman
Freaky
(Hive Bee)
04-05-03 11:52
No 424046
Thanks Rhodium! I already had it written up, so I thought I'd post it in case someone found it useful. I've edited it slightly, since I now realise I was rather out of it when I originally wrote the post. If I work out a better procedure for the third step I'll post it, because there was noticeable pyrazine in the aqueous methyl-methcat HCl solution even after washing twice with toluene. The 100mL acetone washes removed it, but I'd rather it wasn't there in the first place; maybe at 0oC less will form.
I think another very similar cathinone which might be interesting is the indane analogue, as tested by Assholium, but without a full writeup. Antoncho posted Assholium's comments on the final product, which sound promising: Post 252116 (Antoncho: "Re: Short duration Amphetamins", General Discourse)
Anyway, as to what I can remember from last night:
400mg was quite alot to take in one evening, but it wasn't too long lasting so I kept 'topping up'. The rushes after each line were amazing, and I remember feeling very much like I do when coming up on ecstasy, but four times! That beautiful weak feeling, when you just think 'oh, fuck, I feel so fucking good...' It's more euphoric than I remember my first time on the butane methcathinone analogue to be. I felt very compelled to do things, but I was completely unable to keep my concentration on literature searches I was trying to do at the time. I had a very strong urge to socialise, and almost went clubbing, but thought better of it.
An interesting effect was that although I consumed my final dose of 90mg only 1 1/2 hours before going to bed, I was asleep within 30 minutes or so, and woke up having had about 7 hours sleep; totally unheard of for me on stimulants, and more like the way I sleep after taking ecstasy. There were actually some fuzzy visuals when I was trying to get to sleep, but I can't really remember much about them. This morning I feel pretty normal, just a bit tired. I'm sure once I have a shower and something to eat I'll be back to normal. Maybe this could be a candidate for a Short Duration 'Amphetamine'?
Edit: Thanks Barium, although I'm not sure having balls and brains would be such a nice combiation if I actually were a woman.
(Hive Bee)
04-05-03 21:00
No 424130
Well it turned out my acetone washes provided a further gram of fluffy white product after concentration, washing the rather yellow crystals (pyrazine contamination) a few times in acetone and drying. I've edited my post to give the yield after taking this into account, so the overall yield is now 43% from toluene, before recrystallisation... That's good enough for me at least
.
(Hive Bee)
04-05-03 21:33
No 424141
To keep replying to my own post, but I just had an idea which seems quite promising if anyone's willing to try the unusual sounding '4-methyl-4-methylaminorex', and should give very good to excellent yields in each step:
1,2) Follow my procedure for the first two steps: both good/very good yields.
3) Swap the bromine for an azide: should give a good yield, especially since the bromine is alpha- to a ketone. There's probably something in TFSE for this already; I'll search in a minute.
4) Reduce the ketone and the azide simultaneously, possibly with sodium borohydride, to form 4-methyl phenylpropanolamine.
5) Adapt the standard procedure from phenylpropanolamine to 4-methylaminorex; should give an equal yield since the methyl group won't interfere.
Any comments/suggestions? Ritter has a similar procedure to my steps 3 and 4 in ../rhodium /mda.azi
Oh, and I really just have to say a big Fuck You to the UK Government and their stupid drug laws, since I'm high as a kite and there's nothing they can do...
(... sorry, I really had to get that off my chest)
(Hive Bee)
04-05-03 23:50
No 424159
very cool indeed!!
(Hive Bee)
04-06-03 01:57
No 424188
This is for you :
That's a wonderful piece of pioneering research, congratulations man !!
Cheers !
http://www.geocities.com/Hollywood/Set/6
(Hive Bee)
04-08-03 23:27
No 424851
Thanks, everyone!
Hopefully there will be more to come, just not at the rate Barium manages to post...
(Moderator)
04-08-03 23:58
No 424865
It would be interesting to verify the MDMA-like properties... Are you sure about it?
(Hive Addict)
04-09-03 10:11
No 425021
I'll make a batch of it too. I've become very curious about this compound.
Freaky
(Hive Bee)
04-09-03 19:42
No 425142
I've never knowingly tried pure MDMA, but have had on more than numerous occasions 'ecstasy' pills, hence I compared it to ecstasy, and didn't use the more specific term 'MDMA'. I'm sure however that of the various pills I've had over the past 2 1/2 years, at least some were mainly MDMA, so I feel justified in comparing the two.
The first bioassay was written whilst still feeling the effects of the drug. The comparison to ecstasy was comparing the well being and general niceness I felt at the time to how I also feel on ecstasy, so in that respect, it was like ecstasy. I don't think it was the same as ecstasy, but for me at least there were pleasant parallels.
The loved-upness wasn't quite as pronounced, but I felt a strong urge to socialise, and I managed to send a text message to a male friend containg 'love and hugs', something I have a tendancy to do on ecstasy...
The complete lack of residual insomnia also made me think there was something other than a pure stimulant providing the rush: after consuming 600mg (with the final 100mg taken at about 10pm) on Sunday night, I was able to sleep from midnight until 11am with only a few minutes awake in between.
If I give this to anyone else I'll report back on how they like it, but I suspect that Barium will have tried it by then. I would definitely suggest to try step 3 at a lower temperature, say 0oC, for a longer period. I'm going to do exactly this tomorrow (stirring for 24 hours), and although the yield may be lower, I'm pretty sure the purity of the final salt will be increased. If the yield is lower using this modification, I recommend stirring for a longer peroid with no increase in temperature, because I now know that heating causes more harm than to aminopropiophenones than it does to the longer chain aminoketones with the same N-substituents, which I originally based the synthesis on.
(Hive Addict)
04-22-03 19:41
No 428701
Here I sat rolling my thumbs waiting for my 4-methylpropiophenone to be delivered...Boring!!
I suddenly remembered that I had some 4-hydroxypropiophenone. Oh boy! I can try the method with this substrate instead of just sitting here looking stupid. Said and done. Happliy singing a little tune I assembled the glassware, gathered the chemicals...Fuck, I have no bromine! No NaBr or KBr either.
Wait a second. I have some KI...Has the KI/Oxone-system been tried for the insertion of iodine in the beta-position of a propiophenone? Can't remember that I've seen that.What the hell, I'll try it.
KI 2,5g (15 mmol)
4'-Hydroxypropiophenone, 2,26g (15 mmol)
Oxone, 9,21g (15 mmol)
Methylamine, 1,5ml of a 40% aq solution (roughly 20 mmol)
MeOH
Water
To a 250 ml roundbottom flask equipped with a magnetic stirrer was added 2,5g KI, 2,26g 4-OH-propiophenone, 30ml MeOH and 20ml water. All of the KI and most of the propiophenone went into solution within a couple of minutes. 9,21g Oxone was added in portions of 1g. The temperature rose after each addition. The temperature was allowed to reach to 40°C before mild cooling was applied. The color changed from colorless to purplish and some iiodine fumes was visible. Then the color changed to a more red-brown and the temperature dropped back to room temp raplidly. 50 ml cold water wad added to the mixture. This caused a reddish-brown solid to precipitate which was isolated by gravity filtration and washed with some water. The filtrate had a orange tone.
The solid was transferred back to the rinsed 250 ml flask with the aid of 150 ml MeOH. Most of the solids stayed undissolved. 1,5 ml 40% aqueous methylamine was added with a syringe during one minute. Almost immediately the color changed to orange, then to a bright yellow within one minute, then slowly to a pale yellow and finally after five minutes the solution was thick from colorless crystals. During the addition of methylamine the temperature went up from 20-25°C. The solids was removed by filtration and dried to constant weight.
Yield 2,9g of possible 1-(4-hydroxyphenyl)-2-methylamino-propan
Can it be this easy? I have no idea yet if those white crystals really are the cathinone. But there are a few signs indicating this. If the iodination attacked the aromatic ring there would be no reaction with methylamine, and there was. If those red-brown crystals was just a mixture of free iodine and unreacted 4-hydroxypropiophenone there would be no reaction between the iodine and methylamine, and no dramatic color change, again there was.
Can someone shoot me down, please. It just can't be this easy. 40 minutes from start to finished product..
Freaky
(Hive Bee)
04-22-03 21:56
No 428731
Wow, excellent Barium! Without jumping to conclusions of course
, it certainly sounds like you've got something at least resembling the cathinone.I wouldn't be surprised at all if the methylamine reacted as quickly as it did. It reacts rather quickly with the alpha-bromoketone, so the reaction with the iodoketone should be even faster.
I do have one suggestion/question of what your product could contain, something I've just thought of, but I hope I'm wrong: What's the solubility of methylamine hydriodide in methanol? Both of the methcathinone derivatives I've made have been soluble in methanol, yet this precipitated out of solution. Since you used less than 2 equivalents of methylamine, won't any liberated HI react with the free methylamine in solution before the methylamine has a chance to react with the iodoketone, thereby giving a mixture of cathinone product and methylamine HI? Two equivalents of amine are usually used, one as the free acid 'scavenger'.
Of course there must be at least as many moles of cathinone as there are methylamine HI, if there is any methylamine HI at all; no HI will be given off if unless a reaction occurs between the free methylamine and the iodoketone, so you should have at least 50% product in there. Hopefully I'm wrong, and you've managed (once again) an excellent yield of lovely pure crystals! It'd bee wonderful to see such a high yielding simple procedure instead of the two step method I used. Keep us updated if/when you have the chance to do some analysis of the product
.Edit: Unrelated to Barium's work, I made another batch of this at the weekend, but changed the workup slightly. In step 3, once the off-white solid is obtained, it should be rinsed thoroughly with cold THF, which it is insoluble in, to remove all the yellow/orange pyrazine. The white crystals can then be dissolved in methanol/acetone, and once crystallation is complete, a purer product is obtained than by the previous method of recrystallising twice from acetone without the THF wash.
Another point to note is the rather rapid build up of tolerance. For me at least, the 'ecstasy-like' feelings I noted the first couple of times I tried it are pretty much gone. Just to serve as a warning really, 4-MMC is quite a bit less potent than most other stimulants, and isn't suitable for marathon tweaking; I found myself taking 100mg approximately every hour after a couple of days solid use. I still stand by what I said about the first week I tried it though, just be aware that it won't last! The first couple of times were extremely pleasant, although a little short lived. Maybe eating it would be wiser for a longer lasting high.