Ephedrine available products

Propiophenone. Propiophenone [93-55-0] (ethyl phenyl ketone) is a colorless Hquid with a flowery odor. It can be prepared by the Friedel-Crafts reaction of benzene and propionyl chloride in the presence of aluminum chloride (346), or by the catalytic reaction of benzoic acid and propionic acid in the presence of water (347). Propiophenone is commercially available (348), and is sold in Japan at 2700 Y/kg (349). It is used in the production of ephedrine, as a fragrance enhancer, and as a polymerization sensitizer. 

The world war made all these sources of supply difficult of access and stimulated interest in the possibilities of local production. Examination of a number of American species of ephedra had already shown them to be devoid of alkaloids, except for the S. American species E. andina, in which Chavezt found ephedrine, and in the United States attention has been given to the experimental cultivation of imported species, notably E. sinica and E. gerardiana a Moroccan type, E. alenda, was found to contain only ). In Australia experimental cultivation of the Indian species E. gerardiana, E. intermedia and E. nebrodensis has been tried and preliminary yields of 1-35, 1-OS and 0-98 per cent, of total alkaloids respectively have been recorded. In Russia, E. equisetina and E. intermedia are available and are considered to be worth exploitation. In Italy various local species have been found to contain mainly i -ephedrine and that in small amount, but better results are recorded for two species already referred to and which are available in Sardinia, viz. E. vulgaris Rich and E. nebrodensis. ... 

Taking North America as a whole, the declines in the USA were partly offset by rising production in a few super-labs in Mexico. The number of methamphetamine laboratories dismantled in Mexico rose from 10 in 2002 to 18 in 2004 and 34 in 2005. Until recently pseudo-ephedrine and ephedrine were fairly readily available in the country. The Mexican authorities, however, have recently taken measures to counter the diversion of the two chemicals. These efforts reduced the import of ephedrine and pseudo-ephedrine by 40 per cent in 2005 (to 133 mt), with a further reduction of almost 50 per cent (to about 70 mt) expected for 2006.13... 

A number of methods for the synthesis of piperazic acid (7) and related derivatives are currently available as a result of growing interest in natural product chemistry and in their potential in medicinal chemistry. Their chemistry and conformational properties have been comprehensively reviewed. 2451 Racemic piperazic acid is obtained by condensation of penta-2,4-dienoic acid with phthalazinedione and subsequent reductive deprotection of the resulting A,A -bis(phthaloyl)-l,2,3,6-tetrahydropyridazine-3-carboxylic acid.12431 Resolution of racemic piperazic acid is achieved by fractional crystallization of the ephedrine salt of Nl-(benzyloxycarbonyl)piperazic acid from ethyl acetate. 246,2471 A typical route to enantiomerically pure (3S)-piperazic acid 56 starts from chiral 2-amino-5-hydroxyvaleric acid 55 as shown in Scheme 12.1248 Convenient stereoselective syntheses have been reported for 5-hydroxy- and 5-chloropiperazic acids as important constituents of natural cyclic peptides and depsipep-tides.1249,2521... 

Preparative Methods a solution of (l/ ,2S)-(—)-ephedrine (8.25 g, 50 mmol) in anhydrous THF (50 ml) was treated with Borane-Dimethyl Sulfide complex (50 mmol, 5 mL of 10 M solution). The reaction mixture was stirred at 25 °C for 1 h, at which time one equivalent of hydrogen had evolved. The volatiles were removed in vacuo to furnish a white solid, B NMR (3 8 ppm). The solid was gradually heated to 100 °C and maintained at that temperature until the second equivalent of hydrogen had evolved. The product was distilled under reduced pressure to provide the pure oxazaborolidine (86%). An alternative procedure is available. ... 

Both ephedrine and pseudoephedrine remain worry-ingly popular (4) and are widely available without prescription. Based on increasing evidence of the risks of Ephedra self-medication, various national regulatory authorities are currently considering recalling Ephedra products from over-the-counter sales. Oral doses of ephedrine 25-30 mg are often prescribed, for example for orthostatic hypotension. Lower oral doses, present in some cold remedies in tablet form, are unlikely to be efficacious, although they are risky where the drug is... 

Phenylpropanolamine (PPA). Until recently, PPA was widely available in a number of nonprescription cold medications and diet control products. Adverse effects are similar to those described for ephedrine. In response to an FDA warning of increased risk of hemorrhagic stroke, especially in women, PPA has been withdrawn from the market by most manufacturers. Before this withdrawal, PPA was another popular starting product for synthesis of S(-f-)-methamphetamine. PPA is also a metabolite of ephedrine and pseudoephedrine. 

In view of the methamphetamine problem, the Board encourages Governments to limit, as appropriate, the availability of ephedrine and pseudoephedrine to medical needs, by improving monitoring and control measures over domestic distribution channels, as necessary. In that connection, the Board notes that, in the United States, since the recent initiative of the State of Oklahoma to ban the over-the-counter sale of pseudoephedrine tablets, a number of other states in the United States have now taken steps to monitor the sale of such products. 

Norrish Type II reactivity is often a common reaction path for ketones with available Y 7< °sens. Hydrogen abstraction by the excited carbonyl group results in the formation of a 1,4-biradical which can undergo either bond cleavage to reform the carbonyl group and an alkene or bond formation to yield a cyclobutanol derivative. The fragmentation path is followed by the ketone (13). The interest in this reaction is the control which can be exercised on the ketonization of the resultant enol (14). Apparently in the presence of (->-ephedrine asymmetric formation of the final product, (R)-2-methylindanone (15),... 

While this work was in progress an alternate method of asymmetric synthesis via hydride transfer was reported, in which the asymmetric center of the chiral moiety is not sacrificed (3, p. 204). This method uses the reaction product of LiAlH4 and varying amounts of optically active amino carbinols, such as ( — )-quinine, (-f)-cinchonidine, and ( — )-ephedrine, to reduce prochiral substrates. In this system the hydride anion species is sigma bonded to the optically active residue, and a maximum of three hydrides are available for further reaction. The aminocarbinols could sometimes be recovered for reuse. In the instant system the chiral chelating agent forms coordinate bonds to the lithium cation, and four hydrides are available for subsequent reaction. 

Note that, phenylpropanolamine is no longer available in the US and UK and its use has been restricted in many other countries. In addition, because of the associated health risks, the FDA bans combinations of caffeine with ephedrine or pseudoephedrine, and also bans herbal products containing ephedra. 

Nature is the world-leading chemist in synthesizing chiral enantiopure substances, and a vast variety of structures isolated from plant or animal sources are available for the synthetic chemist to use as starting materials. Examples of chiral synthons from nature are amino acids, carbohydrates, hydroxy acids, terpenes, alkaloids, and so on (Figure 1.44). The most representative among them are commercially available compounds, such as ascorbic acid, (+)-calcium panthotenate, (—)-carvone, dextrose, ephedrine hydrochloride, (+)-limonene, L-lysine, mannitol, monosodium glutamate, norephedrine hydrochloride, quinidine, quinine, sorbitol, and L-treonine. The chiral pool strategy uses chiral compounds from nature or products derived thereof (e.g., from fermentation processes). Examples of industrial... 

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