Amphetamine route starting with toluene?

[Nitroxamide]

I spent some time looking around to see if this had been discussed before, and didn't see anything. If I somehow missed it, feel free to delete this thread and flood my inbox with dehumanizing flames. I think I have this in the right section, but if I don't, just remember that I'm new here... :-)

I just switched to Linux (fed up with Windoze), and so I am currently unable to provide any decent diagrams.

Anyway, this is how it would go (keep in mind that I'm a fan of total synthesis). The first step is the one I don't brandish an especially large amount of confidence in, because I am not sure that alkyl halides will add to alkenes. An exact amount of ethene gas would be bubbled through benzyl chloride, which is being rapidly stirred with a magnetic stirrer, yielding phenyl-2-(3-chloropropane). There would be some other junk, such as phenyl-2-(5-chloropentane), but it should be easy enough to distill the phenyl-2-(3-chloropropane) out from the rest. This would then be reacted with sodium hydroxide (nucleophilic substitution), and heated with KHSO4, yielding allylbenzene. The allylbenzene would then be treated with hydrobromic acid to yield phenyl-2-(2-bromopropane); and that would be reacted with sodium azide to yield mostly phenyl-2-(2-azidopropane) (I may be fucking up the nomenclature). I *think* that substitution would be strongly favored over elimination there, but I'm not certain. The phenyl-2-(2-azidopropane) would be reduced with either Raney nickel and hydrogen; or some strong reducing agent such as NaBH4, or LiAlH4, yielding amphetamine. Another possibility would be to use sodium nitrite instead of sodium azide; but that would probably create some nitrite groups, not just nitro groups, and I do not know if nitrite groups can be cleanly reduced to amine groups. Or the whole nucleophilic substitution step could probably be skipped if one was willing to work with hydrazoic acid.

Here's another (hopefully) useful idea of mine that I feel would belong in this thread, due to its subject. Sodium hydroxide would be added to toluene (I'm aware it would barely dissolve), and acetaldehyde would be slowly added (while the toluene is being rapidly stirred with a magnetic stirrer), hopefully eventually yielding some phenyl-2-isopropene (again, I'm not sure if I have the nomenclature right - the double bond in the propane chain would be located between the benzyl carbon and the middle carbon in the propane chain). Certainly wouldn't be the cleanest reaction in the world. This phenyl-2-isopropene would be treated with performic acid, and then heated with dilute H2SO4, resulting in P2P; and it's obvious from there.

Any comments? Please inform me if I've shared something useful, or if I'm just a ranting idiot...
Plutonium is a necessary ingredient in the recipe for nirvana.

[Rhodium]

Your suggestions have no connection whatsoever to reality... Why do you believe acetaldehyde would add to toluene, or ethene to benzyl chloride?

[Nitroxamide]

Sorry if these ideas of mine are bogus... I'll explain why I thought they might be feasible.

As for the benzyl chloride adding to ethene; I was thinking that that reaction might proceed as hydrogen chloride adds to ethene, except with a benzyl group instead of a hydrogen.

As for acetaldehyde condensing with toluene, I thought that  that likely would work, because of the aldol condensation reaction; I thought that if an excess of toluene is used, the acetaldehyde would be more likely to condense with the toluene as opposed to condensing with other acetaldehyde molecules.
Plutonium is a necessary ingredient in the recipe for nirvana.

[Rhodium]

HCl is an acid. Benzyl chloride is not.

Acetaldehyde is an aldehyde. Toluene is not.

I guess you need to do some heavy reading before you try to propose any reactions again.

[Nitroxamide]

Sorry... I have been trying to teach myself, but it's kind of difficult when you don't have anyone to ask questions...

I was looking at that aldol condensation reaction as a reaction between a carbonyl group and a methyl group, if you're wondering where I came up with that.
Plutonium is a necessary ingredient in the recipe for nirvana.

[hypo]

> it's kind of difficult when you don't have anyone to ask questions...

i know how you feel  

i've found "organic chemistry" by vollhardt/schore to be a good
book for learning the basic reaction mechanisms (i wouldn't buy
the new and excessively expensive edition though). combine this
with a well-founded inorganic chemistry book to get a good overview
of the part of chemistry we like most...  

[Nitroxamide]

I haven't become interested in organic chemistry until just recently. I just devoured another 300 pages of my organic chemistry book this last week (I got it brand new for a mere thirteen dollars). Before the last month, I've just been dwelling on inorganic chemistry. I do have lots of references, but I'm the sort of person who's always trying to come up with new ideas, even when I really am not well educated in that field... I guess sometimes I have to make a fool of myself in order to learn...    Example: within my first week of opening up my first chemistry book, I was drawing diagrams of glycerol trichlorate, thinking, "Hm, I wonder how this would be made and if it would be a decent explosive." (it would obviously be suicidal to try to synthesize that).  
Plutonium is a necessary ingredient in the recipe for nirvana.

[Protium]

Do you know that Sigmund Freud used to make bombs in his living room?

The desire to learn itself is worth more than a good idea, don't be afraid to have your ideas shot down if you can learn something from it.
Pr(+)tium

[Nitroxamide]

I don't want to flood the board with inherently flawed ideas, so I'll just share this here. If it is valid, then I guess I'll start a thread on it, but if it's garbage - well, then at least the ignorance is isolated to a single thread.

I was looking at this document:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/peracid.html

I think there's another relatively simple way to make isosafrole glycol.

Cyclohexene can be oxidized with potassium permanganate in cold water for 1.5 hours, giving a 33% yield of cis-1,2-cyclohexanediol. Cyclohexene can also be oxidized with sodium chlorate with osmonium tetraoxide as a catalyst, at 50C for 9 hours, to give a 46% yield of cis-1,2-cyclohexanediol.

I'd think that this could be applied to preparing isosafrole glycol. And I'd think that this could be heated with dilute H2SO4 to yield the beloved MDP2P via the pinacol rearrangment. Comments?

Edit: Corrected idiotic error...

Plutonium is a necessary ingredient in the recipe for nirvana.

[terbium]

I'd think that this could be applied to preparing cis isosafrole glycol. And I'd think that this could be heated with dilute H2SO4 to yield the beloved MDP2P via the pinacol rearrangment. Comments?
Ho, hum. Your posts have quickly grown boring. If you have any decent questions you should post them over in the Newbee Forum.
Baseline Does Not Exist.

[Nitroxamide]

I may not be at the level of many bees here (of organic chemistry knowledge, that is), but I am not a recipe following drone, either...

And if you're wondering why I asked that question: I noticed that tidbit of information in my organic chemistry book; noticed that it could provide an even simpler route to isosafrole glycol; and wondered why Rhodium hadn't posted it on his site, if it was valid. So I wanted to know if I'm overlooking something.

Plutonium is a necessary ingredient in the recipe for nirvana.

[epistemologicide]

stop sighen

read on......


Benzyl Chloride Synthesis by madchemist

Benzyl chloride is made from a substituted toluene and chlorine gas. The rxn
is easy to perform and complete. The only major problem in this is the use of chlorine
gas. It can be very toxic, so please do not do this unless you are under a strong fume
hood, or outside. Benzyl chloride (whether made from toluene or a substituted toluene)
can be the starting point for both phenethylamines and amphetamines.

A substituted toluene is a toluene with susbstituents on the benzene ring. This
reaction is suitable for most, but there probably is going to be those ones with a substitution
pattern that is not compatible with this reaction. Experimentation is the answer to all that.



Chemicals:
toluene (or substituted toluene)
chlorine bleach (or any bleach that contains NaOCl)
Muriatic acid (SWIM gets 31.45% HCl)

Procedure:

1-Place about 300mL of toluene into a flask. Place this on a non-flame heat source.

2-Heat toluene to a rolling boil, why your waiting for it to boil, setup a gassing
apparatus and place into it 500mL bleach. For higher yeilds, reflux of the toluene
instead of just boiling it is better, so it isn't lost by evaporation.

3-Add about 300mL of your muriatic an quickly close the apparatus. This produces chlorine gas.

4-Make sure gas is exiting the gassing tube, then submerge it into the boiling toluene.

5-Ok, well, that was the hardest part. Now you just sit back and relax while the shit reacts.
Of course keep an eye on it. Make sure the tube stays submerged, and keep an eye on the chlorine
gas reaction.

6-When you start to notice the gas reactions to slow down and slack considerably, quickly open it
and add about 50-100mL more of muriatic. Quickly close. This will help produce a little more gas.

7-When it totally slacks off (be careful of suckback), remove the tube from the boiling toluene.
Open the gassing apparatus, and empty it out. Quickly add about 300mL more bleach, and about 150mL
more HCl to it. Quickly close it again, make sure gas is exiting, and gas the toluene once more.

8-When gassing slackens considerably, remove the tube from the boiling solution (which now contains
toluene, benzyl chloride, and HCl acid). While still hot, move to an already setup distillation
apparatus.

9-Distill off al fractions. Collect the fraction that boils around 175-180. This is benzyl chloride.

Notes:
I suppose if one were cheap and didn't have any distillation apparatus, one could just
slowly raise the heat until it reaches benzyl chlorides temp, which I beleive is the highest bp
fraction in the whole mix. But I would go with distillation.
Also like I said yeilds can be higher. This will generally yeild SWIM 90-110g. If a reflux
is used, the toluene won't be lost in evaporation, so more can be converted. Also, the procedure
above was really just slapping things together. I'm sure if one sat down and worked out exact st-
oichiometry to this particular rxn, then yeilds may be in the 90's.

1NaOCl + 1HCl------>1Cl2(g) + 1NaOH
Take the care to add extra HCl, as some gets used by the NaOH produced:
1NaOH + 1HCl------>1H2O + NaCl

1Cl2 + 1PhCH2----->1PhCHCl + 1HCl

FEAR MY GEAR
i cook to save the planet!!

[Nitroxamide]

I see why reaction between toluene and acetaldehyde is not going to occur: toluene can't form an enol.

I am aware, by the way, that there are already explored routes for preparing amphetamine from toluene - chlorination of toluene, nucleophilic substitution with sodium cyanide, then heating the yielded benzyl cyanide with somewhat diluted sulfuric acid (hydrolysis, subsequent anion exchange), yielding phenylacetic acid; which can be converted into phenyl-2-propanone via several routes.    Experimental accounts are always useful, though.

Interesting way of looking at the reaction between sodium hypochlorite and hydrochloric acid (I usually use calcium hypochlorite, by the way - cheaper, and it's sold solid, not in solution). Maybe I'm wrong, but I always thought it went like this:

2NaOCl + 2HCl ----> 2NaCl + 2HOCl
HCl + HOCl <----> H₂O + Cl₂ (UV light drives equilibrium significantly further to the right)

Hypochlorous acid decomposes upon UV light exposure (allowing it to readily oxidize HCl). I've noticed that the reaction between calcium hypochlorite and hydrochloric acid is less vigorous at night (absence of UV light), than in direct sunlight (strong UV light).
Plutonium is a necessary ingredient in the recipe for nirvana.

[raffike]

Toluene to meth is pain in the ass.Raf's been there.He got to benzyl cyanide but then screwed up.Also tolly to benzyl chloride is the most painful step in this synth.Benzyl alcohol to benzyl chloride is nice
For those about to synth,we salute you

[callen]

As we get better acquainted with the procedures and theory associated with certain processes;i.e., as we gain more knowledge and skill...we we also get complacent,and more intolerant and grow a fat head. You will not be credible unless you post reproducible results. Also, A.L.F. sez,"The less seen, the less remembered...and where's that darn cat?"