Dihydrocodeine Alcohol

Catalytic reduction of codeine (2) affords the analgesic dihydrocodeine (7) Oxidation of the alcohol at 6 by means of the Oppenauer reaction gives hydrocodone (9)an agent once used extensively as an antitussive. It is of note that treatment of codeine under strongly acidic conditions similarly affords hydrocodone by a very unusual rearrangement of an allyl alcohol to the corresponding enol, followed by ketonization. 

Catalytic reduction of codeine gives dihydrocodeine and Oppenauer oxidation (a ketone such as acetone and an aluminum alkoxide, the ketone being reduced to an alcohol) gives hydrocodone. Hydrocodone can also be prepared directly from codeine with a metal catalyst, which isomerizes the allylic alcohol to a ketone. Codeine is prepared by methylation of morphine, which is isolated from the opium poppy. Hydrocodone is more potent than codeine. Acetaminophen is a mild analgesic and is discussed in Section 8. 

Dihydrocodeine Bitartrate. Dihydrocodcine is ob-kiincd by the reduction of codeine. The bitaitrate salt occurs as white cry.stals that are soluble in water (1 4.5) and only slightly. soluble in alcohol. Subcutaneously, a dose of 30 mg of this drug is almost equivalent to 10 mg of morphine assn analgesic, with 1 a.ster oreset and negligible side effects. It has addiction liability. It is available in combination with aspirin or acetaminophen fur pain. 

Whereas dihydrocodeine can be converted to 6-chlorodihydrocodide [241], dihydroisocodeine gives only phosphorus-containing products on treatment with phosphorus pentachloride or tribromide, whilst thionyl chloride only effects nuclear chlorination, presumably in position 1, the product giving dihydroisocodeine on reduction with sodium and alcohol [240],... 

Unlike dihydrocodeine and dihydroallo-i/r-codeine-A (q.v.) but like dihydroisocodeine, dihydro->p - codeine-A is resistant to Oppenauer oxidation from which only unchanged alcohol can be recovered [304]. 

Thebainone-B [xm] is best prepared as its hydrobromide by the hydrolysis of dihydrothebaine- [iv] with alcoholic hydrobromic acid [13], but it is also formed by the hydrolysis of the same base with mineral acid in aqueous solution [13], a reaction first reported to give an ill-defined substance, isocodeine [18], and later said to give a coloured, varnish-like substance [3]. Thebainone-B appears to be stable only as its salts in the dry state, the damp salts and free base readily degenerating to brown tars [13]. The ultra-violet spectra of thebainone-A, /3-thebainone-A, and thebainone-B closely resemble those of dihydrothebaine- and codeine, whilst that of thebainone-C is widely different (Fig. 8) and the frequencies of the carbonyl-absorption in the infra-red indicate that whereas thebainone-A and /3-thebainone-A are a /3-unsaturated ketones, the unsaturation is /3 y- in thebainone-B and thebainone-C [13]. On this evidence thebainone-B is allotted the structure [xm]. It can be catalytically reduced to dihydrothebainone [ix], in which the configuration at C-14 is the same as in codeine [13] (cf. the production of dihydrocodeine on reduction of neopine [xiv] [19]). 

Treatment of 14-hydroxydihydrocodeine-B with thionyl chloride results only in chlorination of the aromatic nucleus (cf. the corresponding reaction with the four dihydrocodeine isomers, Chap. IV), but treatment with phosphorus pentachloride affords 14-hydroxy-6-chlorodihydrocodide [xrx], That the hydroxyl group at C-6 is the one that is replaced by chlorine is revealed by the fact that reduction of [xrx] by sodium amalgam and alcohol is attended by rupture of the cyclic ether link, giving 14-hydroxydihydrodesoxycodeine-C [xx], which is readily reduced catalytically to 14-hydroxytetrahydrodesoxy-codeine [xm]. All attempts to reduce [xrx] to a non-phenolic base, or to secure elimination of hydrogen chloride with production of a substance of the desoxycodeine-C type failed [6]. 

The removal of the alcoholic hydroxyl by reaction of the corresponding toluene sulfonate with lithium aluminum hydride has been described Codeine tosylate (CCCXXXVIII) thus leads to A -deoxycodeine (381) and dihydrocodeine to dihydrodeoxycodeine (382). The former reduction may be contrasted with that of a-chlorocodide (CCCXXXIX), which leads to A -deoxycodeine with the same reagent (383). This is in... 

The chemical structures of morphine and heroin in relation to other closely related opiates such as codeine and dihydrocodeine are shown in Figure 2. Morphine has a "phenolic" -OH group in the 3 position and an aliphatic (alcoholic) -OH group in the 6 position. When both -OH groups (3 and 6 positions) are acetylated, diacetyl morphine, better known as diamorphine or heroin is produced. Codeine is the 3-methyl derivative of morphine by substituting the phenolic -OH group with a methyl group in the... 

---