PHENYLACETONES

So let s say, for instance, that some deranged lunatic did the exact opposite of what this book says, and went ahead and got some equipment, a couple of chemicals and some safrole, isosafrole and/or the precursor of their choice. They may very well decide to do something to it to get it farther along the path to final product. Well, currently on the place called Earth, the most widely made precursor for X and amphetamine production is the phenylace-tone. For crystal meth the precursor is called just that phen-ylacetone (a.k.a. phenyl-2-propanone, a.k.a. P2P). For X the precursor would be called 3,4-Methylenedioxyphenylacetone (a.k.a 3,4-Methylenedioxy-phenyl-2-propanone, a.k.a. MD-P2P). Strike knows it should technically be written as MDP-2-P, but Strike has always written it incorrectly as MD-P2P and that is just how stupid-ass Strike is always gonna refer to it. 

That double bonded oxygen (a.k.a. ketone) is very amenable to attack and replacement and is the ideal stepping stone to final product. There are a variety of methods to accomplish this intermediate. Many of which Strike is now gonna iay on you  

METHOD 1 Strike s sentimental favorite. The one Strike has dreamt about so very often. This method involves taking hydrogen peroxide and formic acid to form a temporary intermediate which is subsequently hydrolyzed with sulfuric acid to give the ever-lovely ketone. 

This method is a little labor-intensive because it involves a lot of distilling, but it is so easy to do and the results are absolutely predictable The production of MD-P2P or P2P using this method has been previously described [8,9] except that Strike is going to describe the little things. You know, those little bullshit things that never seem to work their way into official accounts but always cause a lot of stress to the novice chemist. 

324g isosafroie (or 236g propenyl-benzene for meth) and lOOOmL acetone are mixed in a PP container and then poured into a separatory funnel which is situated as shown in figure 9. The acetone solution is added drop by drop into the cold formic solution so that the temperature stays between 10-20°C. The temperature will start to rise a little but the ice bath is well stocked and the dripping is controlled so that the temperature stays below 20°C 

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METHOD 4 This is a P2P recipe that Strike has no hand in. Strike never even knew about it until Strike saw everybody talking about it on the net. But it seems to be extremely popular. Shulgin has written about it. Uncle Fester, Strike understands, has written about it. And there seems to be a lot of posts regarding its high success rates. Most people get started from the method description in the patent literature where they were first published. The following are some representative examples from the U.S. Patent 4,638,094 Process for Producing Phenylacetones ... 

In articles like this one, the scientists don t have the time nor the space to write out the details and amounts of reactants used for every single substrate they tried things on. So they pick just a few of the precursors they tried and use their numbers as an example of how the reaction typically goes. All one does is just substitute an equal amount of their favorite phenylacetone for the one in the example while keeping everything else the same. This will not be too big of a stretch of the old imagination with the first example below. The example ketone is just phenylbutanone. One little carbon more than phenylacetone, but a methyl ketone nonetheless (don t ask). They react exactly the same. As it so happens this first example is also the one using ammonium acetate to make MDA. Sweet ... 

The reaction product is cooled to room temperature, is washed with 10 ml of H2O to the purpose of removing lithium iodide and is then dehydrated over NaiS04. 3.57 g is obtained of dimethoxy-phenylacetone (III), as determined by gas-chromatographic analysis with an inner standard of 4,4 -dimethoxybeniophenone. The yield of ketone (III) relative to the olefin ( ) used as the starting material is of 87.1%. 

The prototype, amphetamine (52), is obtained by reductive amination of phenylacetone by means of ammonia and hydrogen. Isolation of the (+) isomer by resolution gives dextroamphetamine, a somewhat more potent stimulant than the racemate. 

Reduction of phenylacetone in the presence of methylamine rather than ammonia gives methamphetamine (53), an agent similar in action to the primary amine. Alkylation of 53 with benzyl chloride affords the analog, benzphetamine (54). ... 

In the discussion of benzylamines, we have met medicinal agents that owe their activity to some particular functionality almost without reference to the structure of the rest of the molecule. The hydrazine group is one such function in that it frequently confers monamine oxidase-inhibiting activity to molecules containing that group. Such agents frequently find use as antidepressants. Thus, reduction of the hydrazone of phenyl-acetaldehyde (84) affords the antidepressant phenelzine (85). Similar treatment of the derivative of phenylacetone (86) gives pheniprazine (87). ... 

Sulphoxides can be used as phase transfer catalysts, for example, a-phosphoryl sulphoxides (Scheme 24) have been used as phase transfer catalysts in the two-phase alkylation of phenylacetonitrile or phenylacetone with alkyl halides and aqueous sodium hydroxide. However, they are considered to be inefficient catalysts for simple displacement reactions226. 

Recently, it has been reported that methyl 2-pyridyl sulphoxides (10) and related pyridyl derivatives (11) (see Schepie 25) are good phase transfer catalysts for SN2 reactions of various primary or secondary alkyl halides in a two-phase reaction system and for the alkylation of phenylacetonitrile or phenylacetone with alkyl halides in liquid-liquid two-... 

The water is added in order to hydrolyze the a-bromodimethyl ketals that have been produced during the reaction. The ease of hydrolysis of these bromoketals depends on the structure of the ketone. With aeetylcyclohexane (1-cyclohexylethanone) or acetylcyclopentane, stirring with water for 10 minutes is sufficient for complete hydrolysis. In contrast, with phenylacetone (1-phenylethanone) or methyl ethyl ketone (2-butanone), after dilution with water, the addition of 10 equivalents of concentrated sulfuric acid with respect to ketone and stirring for 15 hours at room temperature are necessary for complete hydrolysis. 

Diazomethane, 56,62 Diazomethyl p-tolylsulfone, 57,100 l-Diazo-l-phenylacetone,59, 69 or-Diazosulfones, 57, 97 photolysis of, 57,101 Diazo transfer by phase transfer catalysis, 59,66... 

Figure 2 Scheme of the catalytic mechanism of type I BVMOs. Phenylacetone... 

Figure 3 Illustration of overlapping substrate specificities of four BVMOs. Cyclohexanone monooxygenase (CHMO), cyclopentanone monooxygenase (CPMO), 4-hydroxyacetophenone monooxygenase (HAPMO) and phenylacetone monooxygenase (PAMO). For each enzyme, several typical substrates are...

Genomes were surveyed for the presence of putative type I BVMOs by (1) searching for sequence homologs of phenylacetone monooxygenase and (2) filtering for sequences that contain the type I BVMO-sequence motif2 ... 

Stoichiometric use of a tin reagent to prepare the phenylacetone 4 Toxicity of tin compounds, and operational inefficiency based on high molecular weight of reagent and excessive chromatography required to reject tin residues... 

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