There are no obvious reasons to me that speak against such a scale-down. Of course (...rhetorical...) the yield will probably be a bit lower. Expect that all times from the TIHKAL#26-protocol could get shorter.

You're going from an achiral compound (ketone) to a chiral one (amine), you should (theoretically) end up with a 50/50 mix of R/S.  The racemization occurs when the carbonyl carbon is attached by MeNH2 and forms a tetrahedral intermediate.

So here is a Friedel-Crafts Alkylation that doesn't deal with halogens. Think this could be applied to benzene and propylene glycol to yield 1-phenylpropan-2-ol? Is there any reason why it wouldn't work?

Also if this were to be applied to toluene and propylene glycol would static hindrance keep the methyl group on the opposite side of the ring and yield 1-(4-methylphenyl)propan-2-ol?

Oops, forgot the link.
http://www.franklincollege.edu/pwp/lmonroe/Organic%20Chem/Friedel-Crafts.pdf

Would crude magnesium boride (from B2O3 + Mg) by forming BH3 in situ do the trick for an amide reduction or would the gunk interfere? Or with the proper choice of solvent or additives? Maybe isopropanol with acid gradually added.

The imine function in 4-MAR is stabilized by conjugation as an amidine. Here, that doesn't happen, so you'll get hydrolysis to the ketone, or you'll get rearrangement to 4-MAR itself.

Anybody know MDP2P solubility in toluene? Since If switched to toluene instead of DCM for post-wacker extraction, I've been told to double the amount used per extraction. I know it's not optimised since I've been using less and less each time I run the reaction and still get the same amount ketone at the end. I just don't run the reaction often so I don't know what is the actual required amount to exract. Distilling it afterward is a real pain in the ass so I'd rather keep solvent volume to a minimum. I've searched around online and have found nothing.

By the way, why the hell isn't that damn ketone in the merck. Was happy to put my brand new merck index to use, and I just can't find MDP2P. I'm searching for 3,4-methylenedioxyphenylpropan-2-one, 3,4-methylenedioxyphenylacetone, piperonyl methyl ketone, piperonyl acetone and MDP2P. Checked safrole/MDMA/MDA/isosafrole and piperonal entry and it's not mentioned anywhere. CAS lookup and formula index doesn't list it either. What the hell? I'm surely missing something here...

Thanks in advance

Thanks, Good to know I can use same amount. Having to disassemble the setup many times to refill the RBF with raw ketone (I didn't have big enough flask to do it all at once last time...I've found out that if you fill the flask over 40-45%, you lose an awful amount of time since toluene bumps like there's no tomorrow...Anyway, I've bought bigger flasks now ) is really time-consuming. On top of that vacuum is a must because of high boiling point. After 8 hours, I'm starting to hate hearing the damn pump.

I don't know where to get xylene since I've never looked for it but I suppose I could get it at the same place I get my toluene. Are you sure it makes a big difference ? I don't see how it could. I'm not having any problems with toluene as far as ketone purity/emulsions are concerned. I have no ideas why, but I never had anything else than ketone coming over  ... Density is always over 1.2g/ml...If safrole/isosafrole was to come over, I suppose I would see it considering boiling points differences and the fact that I use a fractionning column to distill it (hmmm just verified and isosafrole boils at the same temp as the ketone...whatever).

I use Methanol though, not DMF...still don't undestand how Xylene can be so superior to toluene though

Oh yeah, damn DCM fucking sucks...Insane pressure buildup in separatory funnels, makes recently greased stopcock leaks, awful emulsions and finally, toxic like hell if you've got no fume hood. Damn I hate it lol...Who cares it's no flammable anyway? I don't understand where it's an advantage as a solvent...I don't go around in the lab smoking cigarettes over my non-sealed toluene bottle while using a Bunsen burner to distill nitromethane

While we talks about it, it remind me how much I hate that part of the synthesis. Seriously it's awful. I think I was traumatized when I started doing this and needed extremely high oil bath temperature to distill the ketone. The pump was a piece of shit pulling something like 25-25.5'' Hg (I only bought it since the guy who sold it to me told me it was pulling 30'' ).... Just to give you an idea, safrole was coming over at 176, and the ketone at 220 or 230, I don't remember exactly. There is always a discrepancy between needed oil bath temperature and distillation temp. . The difference between the 2 temps get worse with increasing boiling point. Let's jusy say that oil bath temperature was about 275-300 when it cames over, and I was paranoiac since vegetables oils supposely have a temp. at which they auto-ignites, but I was never able to find the exact number (Most sites were confused about flask/smoke/fire point) I don't understand why BRIGHT STAR said the flask's content polymerize if temp get over 220. Total Bullshit. When you get it to finally comes over with overexaggerated insulation, cursing and patience, it comes over. I destroyed half the yield a few times with those extremely high temp though, since it will never fucking comes over if the insulation isn't perfect. Anyways ..... Even with a good pump, I'm still always anxious when I reach this step since there is always something happening, even if it's not much.....  Sorry, I'M rambling a bit there


When you says ''you are done within 4h will all the prep'', you means extracting/washing/distilling a ''standard'' (178g safrole/150g benzo) Wacker? If so, W-O-W Might as well go get some xylene right now I'm in Canada and I've honestly never seen toluene/xylene over-the-counter, but I live in a shithole. My specialized paint products shop probably carry it though. Maybe that way they will stop being suspicious about bomb-making (Looks like being young will always be a handicap...The guy at the shop asked me if it was to make TNT ) ... It's funny how which chemicals are OTC differs from country to country...There is nothing in mainstream store around except methanol/acetone/NaOH, but as long as you knows where to look, you will find what you needs...Can't wait to stumble across a shop carrying nitroethane 

You misread, I bought another pump, quite strong too (At least for the kind of work we do...Pulls something likes 29''hg)... A bit too noisy for my situation though. It also can't runs for more than 1.5-2 hours...After that it's like an internal fuse stops everything and I need to let the damn pump cools for 30min Nothing pissing me off more than having that piece of shit suddendly stops when the ketone is coming over nicely....Is a water aspirator that strong? If so, I will seriously looks into buying one. I can't work too late at night with that damn pump...I suppose water pressure variation isn't that bad anyways...Don't worry, I don't heat ketone that high anymore Let's just say that back when I started, there was nothing that was going to stop me from getting the final amine...You should have seen my ketone distillation back then ... Always had the fire extinguisher near me...Was probably borderline dangerous but I sure wasn't endangering anybody else

As for nitroethane, I was joking, I have no idea where to get it. I just remember reading somewhere that americans where crossing the border to buy it in Canada so I figured out there is something going on here.  As for nitromethane, only times I needed it, I got it from RC fuel, but somebody told me you can buy it at a shop where they fix dirtbikes/atv/etc. ..... Since you mentions it's almost impossible for you to get methanol, I suppose you're in Europe. While I have the chance to ask lol, what the hell is the deal with that? How comes it's so unavailable? I can walk into any hardware store around and buy it in 4 liters bottles for 10$ No idea where I can get denatured Ethanol though....Never checked though

As for others methods for getting around distillation, I've never heard about anything. Would be too good to be true. Would be nice if the bisulfite adduct could purity it enough...The wacker oxidation is a really messy reaction, especially when using p-benzo as the oxidant (Never tried any variation though)...Anyway, I've used impure ketone in the past, and yields are fucking shitty...It's already enough Work, might as well do it correctly

I'm going to have to do this step in the next fews days, and this discussion is not making me looking forward to doing it...Can't wait to get more MDA though

Oh and...fuck DCM altogether...That's not a solvent to use without a fume hood. Only chemical that made me ill was DCM. Anyway, I hate when my damn separatory funnel stopcock leak and I don't want my plug to start flying across the room If I lose attention for a second...This reming me this damn solvent screwed up my lab session at school in instrumental chemistry    Oh, and even worse, even If I wanted to use DCM, I would need to distill it from the shitty gooey paint stripper...No thanks This solvent has absolutly ZERO advantages for me.

I didn't know it either until actually feeling some ill effects (Let's be honest, nobody ready dichloromethane's MSDS with careful attention). I was one time working in a confined area with limited ventilation (Extremely stupid, I know, I was in a transition between two ''labs'' emplacement).  I remember back then that when I understood that I was intoxicated by DCM, I've searched for informations, and discovered that's dichloromethane is actually metabolized to carbon monoxide, which can ultimatly results in delayed carbon monoxide poisoning. As I already said, it's the first and only chemical that made me sick so far. No problems with toluene at all. I think it smells nice anyway ... I've included a paper about poisoning


As for MDA preparation, I form MDP2P Oxime with hydroxylamine, then reduce it with an acidic Al/Hg. Works wonder