sodium and mercury have the effect of diminishing the activity of the parent metal, thus slowing dissolution of the reducing species. Vol, Page (year)] are included for each reference for ease of cross reference with cryptic P.L. A variey of Clandestine laboratories which utilize other dissolving metal reduction routes have been infrequently encountered. Enatioselective reduction of oxime ethers promoted by chiral spiroborate esters with an O 3 BN framework is reported for the first time. F.T. Protonation is effected on the electron-rich center via the solvent media in case of NaBH4 or product workup in the case of LiAlH4. Similar correlations apply to the reduction of phenylpropanolamine which the catalytic surface has been coated with SiO2, have revealed that the H-H (which penetrates the SiO2 layer to coordinate with the In the clandestine manufacture of amphetamine and methamphetamine the most popular route is via aluminum-mercury amalgam reduction of the route or intermediate; i.e. The chemistry of these varied approaches has been highlighted with emphasis on the role of the Table 2 is organized by the synthetic catalyst's coordination with molecular H2 and weakening or disrupting of the H-H bond87-88. Several general benzylic alcohols have been reduced to their aliphatic of an "internal electrolytic process". This novel method for the reduction of oximes is vastly preferable to the aluminum-amalgam reductions previously reported. Metal hydride reductions have not captured the imagination of clandestine laboratory chemists like the remainder of the scientific community. In the early and mid 1970's, the Leuckart synthesis, which employs formic acid, was the polular clandestine route to double bond. In metals where higher oxidation states are present (i.e. Additions of large exceses of the amine component in these reactions have been employed to suppress the ketone reduction. This controlled status has resulted in an upsurge in the clandestine manufacture of P2P. Pd, Pt, LiAlH4, HCOOH etc. clandestine laboratories in the United States. This has limited The mechanism of the Leuckart reaction has been studied65,71-72 and shown to be a free radical process initiated by formic acid. discussions on the mechanism of heterogenous catalysis, dissolving metals, hydrides and non-metal reductions used in the manufacture It was found that the reduction of the oxime to the racemic amine 5 could be accomplished in good yield (69%) using zinc-copper couple in warm aqueous ethanol with ultrasonic agitation 8. Metal hydrides function by transfer of a hydride ion to the electron-deficient center (typically carbon) of a However, this "cross application" of chemical synthesis would require a level of chemical knowledge not common among Electron transfer from the metal to a heteroatom results in a radical carbon, which abstracts synthesis of amphetamine and methamphetamine is a reductive step at some point in the synthesis. practice, the three most frequently encountered routes in the United States are: This file is a part of the Rhodium site archive. General LiAlH./Ether 71.7 1.533 1.2. were devoid of extensive references1,2. Unfortunately, the mechanism of the hydriodic acid reduction has not been established. Al, Mg, Zn) dimers may form as a This has been interpreted as the However, in actual Chemical Abstracts citations [C.A. It may be concluded that there are many options available to clandestine chemists (see Fig 1-12). recently been addressed92-93. in clandestine laboratory sites to the open literature. This Aug 2004 static snapshot is hosted by Erowid, The aluminum foil reduction of the Schiff base adduct of P2P and methylamine, The palladium catalyzed reduction of the chloro analog of ephedrine to methamphetamine, The hydriodic acid reduction of ephedrine to methamphetamine. clandestine laboratories. Chem. Heterogenous catalytic hydrogenation of ephedrine to methamphetamine in clandestine laboratories is often achieved with palladium3-8,15,17,39; The actual reduction mechanism does not involve molecular H2, but is, in fact, a result dissolving metal reduction of nitrostyrene with iron and hydrochloric acid52-53 (Fig 4). (U.S.S.R.) 11, 339-343 (1941), J. Appl. Methanmphetamine has been produced in clandestine laboratory sites via NaBH4 reduction of the Schiff base adduct of P2P and methylamime The actual moiety reduced is C-X, where X refers to the halogen3-5,17-19,39,54, sulfate6, phosphate7 or to amphetamine utilizing palladium, platinum and Raney Nickel. However, reduction of a This popularity persists despite US Government This fact is probably the result of their inability to utilize current Chemical Abstracts nomenclature, wherein most literature references Finally, the recurrent use of the terminology "open literature" refers to legitimate, For example, the reduction of a steroidal ketoxime (Table 11, entry 1) with NaBH 4-MoO 3 in MeOH⧸THF gave exclusively the β-isomer. 560, 215-221 (1948), J. Gen. Chem. produce methamphetamine or amphetamine through the reduction of a variety of functional groups; i.e. Alternatives to the Although molecular H2 is produced as the metal dissolves, this is generally considered a Figures 1-12 illustrate the chemical formulas of the chemical ephedrine undergoes a substitution reaction with iodine. Rai and G. Thomas. modified NaBH. W.F. utilized. of amphetamine are oxime reduction12,30-31,35 (Fig 3), nitrostyrene reduction13,32-33 (Fig 4), 2-keto-oxime reductions16,36,38 (Fig 5) and hydrazone reduction23,34 (Fig 6). We use cookies to help provide and enhance our service and tailor content and ads. This suggests that coordination between the organic moiety and the catalytic surface may not be necessary. Noggle, Jr., J. DeRuiter and C.R. Other clandestine routes, although less popular, which have open literature references utilizing heterogenous catalysis for the synthesis Precursors to amphetamine (phenylpropanolamine) and methamphetamine (ephedrine) have been synthesized with the aid of heterogenous catalysis16,38(Fig 5). base reduction, a competing reaction, that of P2P reduction to 1-phenyl-2-propanol, limits the yield of amphetamine or methamphetamine. demercuration procedure route followed by acid hydrolysis to amphetamine (in a clandestine laboratory) as in Fig 1256. synthesis of these controlled drugs, all but ten utilize a reductive approach. the open lliterature. hydrogen from solution to complete reduction. Read full chapter. (Fig 9) to amphetamine67-69 and methamhetamine64-66, no open literature reference directly links hydriodic acid reduction of a Secondly, we felt that a composite reference list would be of assistance in correlating notes or procedures found For whatever reason, this route, which is still very common in Western Europe, lost popularity in the Of 95 references surveyed concerning the Since such diversity exists in these approahes, we felt that following a procedure of Weichet et al55 (Fig 2). (U.S.S.R.) 14, 410-414 (1941). V. V. Patil, E. M. Gayakwad, G. S. Shankarling, J. Org. the United States. Reading Mode The mechanism of forming an oxime from nucleophilic addition of a hydroxylamine to a ketone is taught early on in most courses of organic chemistry. One approach to P2P utilizes a perchlorate8 esters (Fig 1). in Oxime formation from hydroxylamine and ketone: a (computational) reality check on stage one of the mechanism. H2 reduces the C-I bond63. seems remarkable. metal hydrides and non-metal reductions. Chem. This moiety (C-X) may be produced in situ3,17 or syntheized externally, isolated and then reduced4,9,18-19,39,54. Schiff base adduct of phenyl-2-propanone (P2P) and the appropriate amine40-45 (Fig 2). this is a competing reaction. of amphetamine and methamphetamine with over 90 references are presented. catalytic surface89. Chettle, R.S. The title compound 2 is easily available in good yields by selective reduction of oxime 1 with TiCl4/NaBH4 or Na0/n-C3H7OH. Table 1 is organized by the type of catalytic surface or reductive species; i.e. frequency in the Southwestern and Western areas of the United States. However, the mechanism of the carbon-halogen reduction is inconjecture; i. e. Clark, Justus Liebigs Ann. Heterogenous catalysis has been used to reduce the imine bond of Schiff bases formed with phenyl-2-propanone and ammonia or methylamine in Furthermore, hydrogenation of an organic species (incapable of penetrating the SiO2 layer) occurred. result of intramolecular radical combination54,90-91.