Codeine 2- amino

Molecular modifications of the morphine skeleton have produced numerous derivatives with antitussive properties, some of which have become commercially significant. Ethyknorphine [76-58-4] (29), a simple homologue of codeine, is prepared by ethylating morphine. It is pharmacologically similar to codeine but is seldom used clinically. Pholcodine [509-67-1] (30), the morpholinoethyl derivative of morphine, is used as an antitussive in a number of European countries. It is about one and a half times as potent as codeine, has Htde or no analgesic activity, and produces minimal physical dependence. The compound is prepared by the amino alkylation of morphine (48). 

It is known that not all reactions proceed in the same manner on all adsorbent layers because the material in the layer may promote or retard the reaction. Thus, Ganshirt [209] was able to show that caffeine and codeine phosphate could be detected on aluminium oxide by chlorination and treatment with benzidine, but that there was no reaction with the same reagent on silica gel. Again the detection of amino acids and peptides by ninhydrin is more sensitive on pure cellulose than it is on layers containing fluorescence indicators [210]. The NBP reagent (. v.) cannot be employed on Nano-Sil-Ci8-100-UV2S4 plates because the whole of the plate background becomes colored. 

Alkaloids are compounds that contain nitrogen in a heterocyclic ring and are commonly found in about 15-20% of all vascular plants. Alkaloids are subclassified on the basis of the chemical type of their nitrogen-containing ring. They are formed as secondary metabolites from amino acids and usually present a bitter taste accompanied by toxicity that should help to repel insects and herbivores. Alkaloids are found in seeds, leaves, and roots of plants such as coffee beans, guarana seeds, cocoa beans, mate tea leaves, peppermint leaves, coca leaves, and many other plant sources. The most common alkaloids are caffeine, theophylline, nicotine, codeine, and indole... 

Cortisol into 7- 3-hydroxycortisol. Epoxidation Benzene into benzene 1,2-epoxide. N-oxidation Drug containing amino groups can undergo N-oxidation i.e. imipramine into imipramine N-oxide. 0-dealkylation This reaction probably Involves formation of an unstable hydroxy methyl Intermediate I.e. codeine Into morphine. 

Crowther and Henion have reported the SFC assay of polar drugs on packed columns using mass spectrometric detection [10]. Their method was shown to be suitable for a multicomponent mixtures containing nonpolar and polar analytes. They mentioned that one of the advantages of SFC versus HPLC was the faster column reequilibration time. In this method, silica, amino, nitrile, and diol packed columns (20 cm x 2.1 mm ID) were used. Cocaine, codeine, caffeine, methocarbamol, phenylbutazone and ox-yphenbutazone were separated on one or more of these columns and mass spectra were obtained. 

Amino group containing drugs (codeine phosphate, Bare silica Micra, 3 pm Acetonitrile-5-20 mM Tris-HC1, pH 7.5-10 (90 35-10) 270 mm x 65-75 pm i.d. 200 mm packed length 143... 

Derivatives of 14-hydroxydihydrocodeinone have been converted into 6a- and 6/ff-amino-compounds by condensation with benzylamine and then reduction and hydrogenolysis of the resulting Schiff-bases,195 and also into their hydrazones.196 Codeine and ethylmorphine have been nitrated and sulphonated at position 1197 and fluoro-compounds of structures (103 R = H), (103 R = OH), (104 R = H), and (104 R = OH) have been prepared from dihydrocodeinone and 14-hydroxy-dihydrocodeinone by treatment with diethylaminosulphur trifluoride.198... 

Amino group-containing drugs codeine phosphate, ephedrine hydrochroride, thebaine, berberine, hydrochloride, jatrorrizine hydrochloride, cocaine hydrochloride... 

Nitromorphine is given by direct nitric acid nitration of morphine(163) however, with nitric oxide, 2-nitromorphine results. These compounds may be elaborated further to amino derivatives and by diazomethane treatment to the corresponding codeines. Codeine with concentrated H2S04 at ambient temperature afforded the zwitterion 68, which in nitric acid gave 1 -nitrocodeine. A similar conversion was achieved with ethylcodeine and hydrocodone.<164)... 

Fig. 7.6. Separation of heroin and some common adulterants and contaminations Column amino-propyl bonded silica (S5NH.)(Phase-Sep) (250x4 mm ID), mobile phase acetonitrile - 0.005 M tetrabutylammoniurn phosphate (85 15), flow rate 1 ml/min, detection UV 284 nm. Peaks 1, noscapine 2, papaverine 3, caffeine 4, heroin 5, acetylcodeine 6, 6-0-acetyl-morphine 7, codeine 8, strychnine 9, morphine, (Reproduced with permission from ref. 93, by the courtesy of Journal Chromatographic Science)...

Nitration of codeine sulphonic acid affords 1-nitrocodeine [339, 350], whilst nitration and sulphurous acid reduction of a-codeine-N-oxide sulphonic acid gives a-nitrocodeine, which can be reduced to 1-amino-codeine [339, 350, 341], Bromination of the a-N-oxide sulphonic acid gives a perbromide of unknown constitution [339, 350] that is reduced to bromocodeine dibromide C18H20O3NBr3 [295]. 

The Stork group reported the synthesis of racemic codeine and thebaine utilizing the intramolecular Diels-Alder reaction as the key transformation in 2009 [45]. The key features of their synthesis are (1) a direct construction of a phenanthrofuran skeleton (A-B-C-E tetracyclic system) by the intramolecular Diels-Alder reaction of a diene tethered to the benzofuran ring and (2) a formation of the D-ring by the intramolecular SN2 reaction of an amino-mesylate. 

The aqueous sulfuric-chromic acid oxidation of codeine has long been known to give a hydroxycodeine in which the newly introduced hydroxyl is either at position 9 or 10. Prom the fact that the methiodide of the substance (A) requires quite vigorous treatment with base to produce the ketonic methine, it was always clear that it could not be a carbinolamine Such a substance would form a methiodide (B) that would merely be the hydriodide of the amino ketone and would thus be instantaneously transformed into free amino ketone upon treatment with dilute base ... 

A further patent for the production of codeine, via codeinone, from thebaine has been published. " Codeine has been shown to be oxidized by manganese dioxide to 14-hydroxycodeinone the reaction is presumed to proceed via codeinone since 6-acetylcodeine is not affected by the same reagent. 6-O-Methanesulphonyl-dihydrocodeine has been shown to react with tetra-butylammonium fluoride, lithium chloride, and lithium bromide, with inversion at C-6, to give the related 6-halogeno-dihydrocodides, but when the ester is heated with sodium iodide in dimethylformamide the product is A -deoxycodeine (deoxycodeine-C) (143). Reductive amination of naltrexone with 2,2 -dihy-droxydiethylamine and sodium cyanoborohydride yields the 6-amino-compound (144 R = OH), which can be converted by carbon tetrachloride and tri-... 

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