Codeine N-oxide

N-oxides of morphine and several morphine derivatives have been prepared by the action of isopropanol/H202 on the appropriate tertiary base.(156) At best, the N-oxides were weak analgesics, but dihydromorphinone N-oxide and codeine N-oxide did exhibit good antitussive properties/157 ... 

An isomer of 1-nitrocodeine, a-nitrocodeine can be prepared from codeine-N-oxide sulphonic acid. It gives 1-aminocodeine on reduction. Nitration of dihydrocodeine [241] and dihydrocodeine sulphonic acid [341] gives 1-nitrodihydrocodeine. 

Codeine-N-Oxide and its Derivatives Like other tertiary amines, on heating with 30 per cent, hydrogen peroxide codeine is converted to an N-oxide this is reduced to codeine by sulphurous acid [348]. A dimolecular oxide C36H4409N2 7H20 is obtained from the not too prolonged treatment of the base with 1-5 per cent, hydrogen peroxide on the water-bath it is transformed to a raonomolecular oxide by heating with alcohol and concentrated hydrochloric acid [349]. 

When codeine-N-oxide is sulphonated, two isomeric codeine-N-oxide sulphonic acids, a- and /3-, are obtained the former being transformed to the latter by alkali. Both yield the same codeine sulphonic acid on reduction with sulphurous acid, ex- and /3-Codeine-N-oxide sulphonic acids and codeine sulphonic acid are converted to codeine by superheated steam and to /3- and y-codeine sulphonic acids by cold concentrated sulphuric acid [339, 350],... 

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 isomerio codeine-N-oxide sulphonic acids are not derived from i/r-oodoine, as i/r-codeine-N-oxide sulphonic acid is different from both [341]. It has boon suggestod that their structures are [xlu] and [xnn] [330]. 

Codeine-N-oxide sulphonic acid on heating with potassium chromate is converted to norcodeine sulphonic acid, which yields norcodeine on heating with superheated steam [352] (the nature of this change was not at first appreciated [339, 350]). Codeine-N-oxide likewise yields norcodeine and formaldehyde when oxidized with potassium chromate [352]. 

Two sulphonic acids are obtained by the sulphonation of i/<-codeine-N-oxide [295, 341] and bromination of these, followed by decomposition of the perbromide with sulphurous acid, gives bromo-i/i-codeine dibromide, C HgoOjNBrj, which can be reduced catalytically to tetra-hydro-i/ -codeine [295],... 

Two sulphonic acids result from the sulphonation of allo-i/ -codeine-N-oxide, and these on bromination and reduction of the per bromide are converted to bromoallo-i/r-codeine dibromide [295]. 

Simultaneous codeine, benzoic acid, p-aminophenol, codeine N-oxide, codeinone... 

Interfering bromo-STP, codeine-N-oxide, ethylmorphine, 4-hydroxyamphetamine, morphine, morphine-N-oxide, normetanephrine, 2-phenethylamine, prolintane, STP... 

Simultaneous amphetamine, benzphetamine, benzylmorphine, bromo-STP, buprenor-phine, caffeine, codeine, codeine-N-oxide, dextromoramide, dextropropoxyphene, diethyl-propion, dihydrocodeine, dihydromorphine, dimethylamphetamine, ephedrine, ethohep-tazine, ethylmorphine, etorphine, fenethyline, fenfluramine, fentanyl, hydrocodone,... 

Codeine hydrochloride Codeine N-oxide Codeine sulfate Dihydromorphine... 

Simultaneous acetylcodeine, amphetamine, benzphetamine, benzylmorphine, bromo-STP, buprenorphine, chlorphentermine, codeine, codeine-N-oxide, dextromoramide, dextropro-poxyphene, diamorphine, diethylpropion, dihydrocodeine, dihydromorphine, dimethylam-phetamine, dipipanone, ephedrine, epinephrine, ethoheptazine, ethylmorphine, etorphine, fencamfamin, fenfluramine, fentanyl, hydrocodone, 4-hydroxyamphetamine, levorphanol, mazindol, meperidine, mephentermine, mescaline, methadone, methamphetamine, meth-ylenediojQramphetamine, methylephedrine, monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-N-oxide, naloxone, norcodeine, norlevorphanol, normetanephrine, normethadone, normorphine, norpethidine, norpseudoephedrine, noscapine, o codone, papaverine, pemoline, pentazocine, 2-phenethylamine, phenoperidine, phentermine, phenylephrine, phenylpropanolamine, pholcodeine, pipradol, piritramide, prolintane, pseudoephedrine, STP, thebacon, thebaine, trimethoxyamphetamine, tyramine... 

FIGURE 5.21 IR spectra of (1) codeine N-oxide, (2) N-methylcodeinimn iodide, (3) 6-0-acetylcodeine, (4) barbituric, and (5) thiobarbituric derivatives. 

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