Smurf/ing doesn't just refer a to errand boys but can also mean the action of going round many different pharmacies, picking up PSE at each one. This being a practical solution primarily in the UK due to reporting list rules in the US. Theres no requirement or even ever requests to show ID for pseudo. If it ever does get cracked down on then the govt are actually more likely to be letting themselves in for more
than they -bargained for. INCREASING rather than decreasing the national total supply, and thus increasing availability. Because generally the quantities of pseudo are limited, to a certain degree in availability , ounces and multiples of ounces, depending on how patient the cook is, weather or not there are runners employed to smurf supplies in greater quantities than a single chemist on their own can practically manage etc.
But if that route were either taken out either wholly or in part, that would force cooks to use alternate routes. P2P (synonymous-PMK, phenyl methyl ketone, BMK-benzyl methyl ketone. P2P being short for 1-phenyl-2-propanone or 1-phenyl-propan-2-one, same thing, different nomenclature), for which multiple routes exist. This is then reductively aminated using methylamine as the amine source (for meth) although other primary alkyl amines could be used, such as ethylamine to give N-ethyl amphetamine which is not bad at all, quite smooth and less jittery than meth. Although the amphetamines produced via reductive amination, at least the usual routes, are racemic, there probably are enantioselective reduction methods available, although a chiral synth is more than a commercial cook is very likely to try. or beyond them. The alternative to using some kind of chirally directing reducing agent which IMO may succeed although I'd need to look into it if I decided to try.
The alternative would be to waste part, the laevorotatory isomer of the finished amphetamine product and resolve the isomers afterwards by for example selective crystallization of the D- or L-speed with the
appropriate isomer of tartaric acid, as this is a chiral organic acid, and it will co-crystallize out with the corresponding isomer of the chiral product, D-tartaric acid will form crystalline salts with dextro- but not laevo-amphetamine/meth etc and L-tartaric acid will only crystallize with laevo, not dextro isomers of a chiral amine.
Doesn't matter which way round one goes IMO, take one half of a binary mixture out of the pair, get left with the other.
Although doing this, whilst it will allow for the selective isolation of the desirable D-'phet it does leave one with the other half as dross. IIRC deamination is possible to reform P2P and rerun the synth again to claw
back some more D-meth /D-amphetamine for one's available resources.
Alternatively theres the knoevanagel (Henry) condensation reaction instead of P2P. Its a lot easier to do than trying to resolve a racemate end product and using (I THINK) a chiral amine base as the catalyst may well produce an enantiopure product. The knoevanagel/henry is done by condensation of a benzaldehyde and and a nitroalkane catalyzed by an amine base, to give an intermediate beta-nitroalkene, if nitromethane is chosen, then the result is a beta-nitrostyrene, and this on reduction will give a phenethylamine. Phenethylamine itself, not active in vivo due to being eaten up instantly by monoamineoxidase-A results from condensation of benzaldehyde and nitromethane. Substituted benzaldehydes are more interesting here, for the capacity to produce all manner of substituted phenethylamines, many having psychedelic activity, such as mescaline and its analogs, 2C-B, 2C-I, 2C-D, 2C-E, 2C-T-7, and many more besides.
The use of nitroethane instead of nitromethane results in a beta-nitropropene as an intermediate, on reduction this will yield an amphetamine. Not sure how chirally selective it is generally speaking, as I've only used the reaction with nitromethane. And owing to the lack of the alpha-methyl group on amphetamine, which is the location of the chiral carbon, the phenethylamines are not chiral. Outside the realms
of those having a ring substitution pattern permitting the presence of a chiral center. Most of them this doesn't apply to though, and are achiral.
Its a very easy reaction to run though, dissolve the benzaldehyde and the nitroalkene in solvent, methanol, preferably dried over anhydrous magnesium sulfate (epsom salts are hydrated MgSO4, spread out on baking foil on a baking tray and whack it in the oven until it turns white and crunchy, its quite obvious when this has been performed to completion. Once its cooled, a bit it can be added to the methanol, and it allowed to sit, and settle out, having bound much of the water, it'll improve yield some, although its not at all essential. The rxn can also be performed in neat nitromethane as a solvent, or nitroethane if making amphetamines, but since these are precursors too, it makes far more sense to use the cheap and throwaway MeOH and use only the requisite molar quantity of your nitroalkane. Then add your amine catalyst, pref. a secondary or tertiary amine. Ammonium acetate is used as well too sometimes, although there are better ones by far. I favor triethylenetetramine myself, TETA, can be isolated from some epoxy glue kits as the hardening compound, other options include cyclohexylamine, tert-butylamine, ethylaminediamine diacetate aka EDDA. Ammonium acetate does at least have the advantage of being very available, from glacial acetic acid and ammonia. Or just boiled down white vinegar to provide the acetic acid until as concentrated as it can be made. For best yields though, different substrate aldehydes seem to have different
preferences with respect to catalyst chosen. although never having heard of the use of TETA before, it was to hand and has given very impressive results w/nitromethane knoevanagels.
For the reduction of the nitroalkenes, there are many ways. Lithium aluminium hydride is quick, its clean, its selective and doesn't result in any horrible byproducts or nasty waste. It does need care in its use
however. Flame dried glassware, solvents (ethers, usually the cyclic ether tetrahydrofuran as it forms a complex with the LAH, diethyl ether is another good bet), regardless of which is chosen it must be rigorously dried and distilled over lithium (more available to most people) or sodium wire/sodium granules to scrub the last little traces of water out of your solvent. Drying the glassware in the oven is just fine, and a blanket of argon (welding gas bottles, it can be dried by passage through conc. sulfuric acid, then scrubbed of any acid traces by further passage through powdered caustic soda) because LAH is pyrophoric
and likes to burst into intensely hot, hard to put out metal fires. That, in highly volatile and flammable THF or ether really wouldn't be pretty. And even less attractive a prospect when one has an expensive investment of reagents and precursors in that etherial solution, undergoing reduction.
Another, easier reduction, although its suitable for nitrostyrenes, not sure if its suitable for nitropropenes, is to use aluminium amalgam, aluminium is a very reactive metal indeed, but so much so that
it forms an inert, but very thin surface layer of oxide that passivates the metal and retards further oxidation. Mercuric salts (I believe the metal can be used but would have to check) strip the oxide layer and prevent it from reforming (actually so effectively, that application of a bit of Hg to a block of aluminium by stopping the instantaneous repassivation, and damaging the protective layer, allows the air to rapidly attack the Al, the corrosion spreads like a plague, literally, like a creeping border of bacterial infection or decay, and it really does creep, slowly, for a solid block, as though a living disease were at work, assaulting
the Al, and you just get it crumble away. For this reason, transport of mercury and items containing it, is prohibited on aircraft, which are made out of aluminium due to its light weight and strength, etc.
The plane, if said Hg were carried thereon, and it were to get loose, could quite literally, cause the plane to fall apart in mid air. Bit of a nasty thought, eh? sitting there in your seat, eating your in-flight meal, only to find yourself in your seat, but your seat no longer having a plane attached anymore!!
Hg is toxic, but it does work, Al foil, chopped into squares and crumpled up into balls, doesn't need to be super tight, or too loose, controlling the available surface area accessible to the mercury salt and the surrounding environment, and then addition of substrate, reflux, although its exothermic and can start to supply sufficient heat to the reaction to keep it going once started. So temperature control is needed.
Alternatively, there are dissolving metal reductions available, some more useful on some substrate types than others. HCl, or glacial acetic acid and the likes of zinc or iron powder, never done it though.
Another one thats looking interesting, not tried it, but reading on the use of the lanthanide samarium as the triiodide or presumably other nonfluorine trihalides of samarium, it looks like it might have real serious potential for the reduction of beta-nitrostyrenes/nitropropenes.
If anyone's interested, just say so, and I can post up some of the most facile, and from-scratch routes to nitroethane. NitroMethane can be had from commercial RC model racing car fuel, usually mixed with both methanol, which is fine in the knoevanagel/henry reaction anyway, and oil to lube the engine up which isn't, but which can easily be separated via distillation of the nitro under vac (careful, nitromethane can be explosive if its mistreated, but its not too dangerous to allow for as a procedure, just care should be taken), and small quantities of benzaldehyde can be had from many artificial almond essences, or by oxidation of toluene , which again if anyone wants to try, just say so and I'll post up some protocols for doing it at home:)
And another route to amphetamine couldbe perhaps from propiophenone and pthalimide, to prepare pthalimidopropiophenone. Reduction of both imide to imine to amine and subsequent or at the same time, reduction of the carbonyl group might work. then cleavage off of pthalic acid in acid. Certainly pthalimidopropiophenone itself apparently is metabolized in vivo to pthalic acid and beta-ketoamphetamine (cathinone), the same compound as plays the role of main active stimulant in the plant known and chewed as 'khat', Catha edulis.
