Of ephedrine

This experiment describes the quantitative analysis of the asthma medication Quadrinal for the active ingredients theophylline, salicylic acid, phenobarbital, ephedrine HGl, and potassium iodide. Separations are carried out using a Gi8 column with a mobile phase of 19% v/v acetonitrile, 80% v/v water, and 1% acetic acid. A small amount of triethylamine (0.03% v/v) is included to ensure the elution of ephedrine HGl. A UV detector set to 254 nm is used to record the chromatogram. 

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. 

To avoid the difficulty of variation in alkaloidal content liable to occur in commercial Ephedra a proposal.has been made in India for the manufacture of a standardised extract representing 5 per cent, of the weight of the crude drug and containing 18 to 20 per cent, of the total alkaloids. Both in India and China experimental extraction of ephedrine has been started. ... 

For the assay of ephedrine in the total alkaloids a colorimetric method based on the biuret reaction was used by Feng and Read and is described in detail by Feng. Krishna and Chose separated ephedrine and iji-ephedrine by treating the dry mixed hydrochlorides with dry chloroform in which the ephedrine salt is virtually insoluble and the -ephedrine salt soluble. ... 

For the estimation of ephedrine in its salts or simple solutions, titration methods and a Kjeldahl estimation have been described by various authors. The formation of iodoform from ephedrine has been proposed as a method of estimation by Sanchez, and biological methods have been used by several authors. ... 

With potassium ferricyanide and sodium hydroxide solution ephedrine forms benzaldehyde. A solution of the hydrochloride gives with copper sulphate and sodium hydroxide solutions, a purple coloration extractable by ether, leaving the aqueous layer blue. A solution of ephedrine base in chloroform on standing is partially converted into ephedrine hydrochloride. ... 

Much attention has been given to devising tests for a) the identification of ephedrine, (i) means of distinction between ephedrine and -ephe-drine and (c) the recognition of the dZ-form of ephedrine.Ephedrine, according to Kirkpatrick, ) is polarographically inactive. 

Attempts had been made from 1904 onwards to synthesise ephedrine or ephedrine-like substances, but it was not imtil 1920 that two substances now generally accepted as optieally inactive forms of ephedrine and i/i-ephedrine were obtained by Eberhard. The proeess used was the reduetion of a-methylaminopropiophenone by (a) sodium amalgam and dilute hydrochloric acid and (b) hydrogen in presenee of palladised ehareoal ... 

Mannich condensation of the primary amine corresponding to ephedrine (32) with formaldehyde and m-methoxyacetophenone yields oxyfedrine (33), this agent retains the vasodilating activity of ephedrine and is in fact denoted a coronary vasodilating agent. 

Addition of a hydroxyl group to the aromatic ring of ephedrine as well as changing the substitution on nitrogen leads to a compound whose main activity is to raise blood pressure. Thus, lormation of the Shiff base of the m-hydroxy analog of 30 with bcnzylamine (34), followed by catalytic reduction, yields metar- uiiinol (35). When optically active hydroxyketone is employed in... 

Acylation of norephedrine (56) with the acid chloride from benzoylglycolic acid leads to the amide (57), Reduction with lithium aluminum hydride serves both to reduce the amide to the amine and to remove the protecting group by reduction (58), Cyclization by means of sulfuric acid (probably via the benzylic carbonium ion) affords phenmetrazine (59), In a related process, alkylation of ephedrine itself (60) with ethylene oxide gives the diol, 61, (The secondary nature of the amine in 60 eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization as above affords phendimetra-zine (62), - Both these agents show activity related to the parent acyclic molecule that is, the agents are CNS stimulants... 

Pseudoephedrine is an isomer of ephedrine in which the hydroxyl group is on the other side of the molecule. 

Interactions with caffeine and aspirin can increase the effects of ephedrine. Norepinephrine works in part by increasing the levels of cyclic aminomethyl propanol (AMP) in cells. Caffeine inhibits the enzyme that breaks down cyclic AMP. Together, ephedrine makes more cyclic AMP, and caffeine prevents it from breaking down. Aspirin inhibits the receptors that turn off release of norepinephrine. 

Oxazolidines 130 were obtained by reaction of (-)ephedrine with aldehydes under microwave irradiation and in the presence of molecular sieves in order to remove the water formed in the reaction (Scheme 46) [84,85]. As expected. 

Schematic profile of the titration curve for a weak base B titrated with hydronium ions. The pH values are those for titration of ephedrine, a weak base that is the active ingredient in many decongestants.

Ephedrine, a weak base, is the active ingredient in many commercial decongestants. To analyze a sample of ephedrine dissolved in 0.200 L of water, a chemist carries out a titration with 0.900 M HCl, monitoring the pH continuously. The data obtained in this titration are shown in Figure 18-6. Calculate Zj, for ephedrine and determine the pH of the solution at the stoichiometric point. 

Imaz, C., Navajas, R., Carreras, D., Rodriguez, C., and Rodriguez, F.A., Comparison of various reversed-phase columns for the simultaneous determination of ephedrines in urine by high-performance liquid chromatography, /. Chromatogr. A, 870 (1 2), 23, 2000. 

Introduction Since we had already developed the novel asymmetric addition of lithium acetylide to ketimine 5, we did not spend any time on investigating any chiral resolution methods for Efavirenz . Our previous method was applied to 41. In the presence of the lithium alkoxide of cinchona alkaloids, the reaction proceeded to afford the desired alcohol 45, as expected, but the enantiomeric excess of 45 was only in the range 50-60%. After screening various readily accessible chiral amino alcohols, it was found that a derivative of ephedrine, (1J ,2S) l-phenyl-2-(l-pyrrolidinyl)propan-l-ol (46), provided the best enantiomeric excess of 45 (as high as 98%) with an excellent yield (vide infra). Prior to the development of asymmetric addition in detail, we had to prepare two additional reagents, the chiral modifier 46 and cyclopropylacetylene (37). 

Ma Huang (Ephedra sinica) is another potentially harmful herb that is available in the United States. Claims of utility of Ma Huang for the treatment of bronchial asthma, cold and flu symptoms, fevers or chills, headaches and other aches, edema, and lack of perspiration have been made [23], Ma Huang contains approximately 1% of ephedrine and therefore possesses central nervous stimulatory potential [24], However, ephedrine is difficult to extract and purify from Ma Huang, so it presently has no street value. 

Direct alkylation of the appropriate aryl-ethanolamine is, of course, widely used as, for example, in treatment of ephedrine (13a) with ethyl iodide to give the adrenergic agent, etafedrine (13b), or with cinnamyl chloride to give the muscle relaxant, cinnamedrine (14).10 Likewise, alkylation... 

The transformation of the cyano group could also introduce a new chiral center under diastereoselective control (Figure 5.13). Grignard-transimination-reduction sequences have been employed in a synthesis of heterocyclic analogues of ephedrine [81]. The preferential formation of erythro-/3-amino alcohols may be explained by preferential hydride attack on the less-hindered face of the intermediate imine [82], and hydrocyanation of the imine would also appear to proceed via the same type of transition state. In the case of a,/3-unsaturated systems, reduction- transimination-reduction may be followed by protection of the /3-amino alcohol to an oxazolidinone, ozonolysis with oxidative workup, and alkali hydrolysis to give a-hydroxy-/3-amino acids [83]. This method has been successfully employed in the synthesis L-threo-sphingosine [84]. 

Effenberger, F. and Eichhorn, J. (1997) Stereoselective synthesis of thienyl and furyl analogues of ephedrine. 

Figure 14.9 Reaction scheme for production of (—)-ephedrine based on enzymatic C—C bond formation using Saccharomyces cerevisiae coupled with a chemical reductive animation...

A similar reaction of (-)-ephedrine (42) was reported to give 2-chloro-l,3, 2-oxazaphospholidine 2-oxide either as a single diastereomer (25,45,5R)-73a [51-53] or as the isomeric pair 73a,b, which could be separated by chromatography over silica gel (Scheme 23) [32, 54],... 

Treatment of (-)-ephedrine (42) with a variety of aIkyl(aryl)phosphonic dichlorides 106a-d afforded the isomeric pairs of the corresponding 2-alkyl(aryl)-2-oxo-l,3,2 oxazaphospholidines (Scheme 31 and Table 1) [32, 62-65],... 

Treatment of (-)-ephedrine (42) with methylthiophosphonic dichloride afforded a mixture of the isomeric 2-methyl-l,3,2 oxazaphospholidine-2-thiones 120a,b, from which the pure isomers could be separated in approximately equal quantities by chromatography over silica (Scheme 34) [32],... 

The condensation of enantiomerically pure amino alcohols (derived from amino acids) with aldehydes to furnish 1,3-oxazolidines was studied by Kuhnert and Danks in 2001 (Scheme 6.212) [382], Under solvent-free conditions, microwave irradiation of equimolar mixtures of the amino alcohol and the aldehyde for less than 3 min provided high isolated yields of 1,3-oxazolidines with excellent diastereoselectivity. In the case of (-)-ephedrine, prolonged microwave irradiation (3 min) produced quantitative conversions and high diastereoselectivities. For shorter irradiation times (80 s) mixtures of the two diastereomers were obtained with moderate conversions. 

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