Codeine 1-chloro

Apomorphine (— black), azatadine, benorylate, bisacodyl, buprenorphine, butriptyline, captodiame, chloro-pyrilene, chlorpromazine, clofazimine, codeine, diamorphine, diethylthiambutene, dihydrocodeine, dimeth-indene blue), dimethoxanate, doxorubicin, doxylamine, ethopropazine, ethoxazene, guaiphenesin, guanoxan, hexocyclium methylsulphate, mepyramine, 6-monoacetylmorphine, morphine, nalorphine, nor-morphine, oxprenolol, oxyphenisatin, pecazine, penthienate, perazine, perphenazine, phenoxybenzamine, phenyltoloxamine, pholcodine, pimozide, pipoxolan (-> grey), prochlorperazine, procyclidine, promazine, promethazine, proquamezine, solanidine, thenium, thiopropazate, tricyclamol, trimeprazine, viloxazine... 

But what really takes place in these instances is this the codeine undergoes a chlorine substitution, and gives rise to a basic chloro-codeine, with which the hydrochloric acid continues combined. 

Dihydro-i/< -codeinone is obtained in 40 per cent, yield by the Oppenauer oxidation of dihydroallo-with phosphorus pentachloride gives 8-chloro- and 1 8-dichlorodihydrocodide, which are also produced in the same way from dihydro-i/ -codeine-A thionyl chloride effects chlorination in the aromatic nucleus only. With phosphorus tribromide it apparently suffers replacement of the hydroxyl group by bromine, loss of hydrogen bromide, and demethylation, as the product is desoxymorphine-D [240] (see Chap. VIII). 

Bromination of codeine results in 1-bromocodeine and finally in a tribromocompound chlorination with chlorine water is more complex and gives resinous products [1, 2], Apomorphine [m] is formed by heating morphine and concentrated hydrochloric acid in a sealed tube above 100° C., and, together with methyl chloride, from codeine under the same conditions [3-6] (see Chap. XXII). When codeine is heated on the water-bath with concentrated hydrochloric acid, however, replacement of the hydroxyl group by chlorine occurs and a-chlorocodide is produced [7-8] this may be prepared in other ways from codeine and i/r-oodeine, and can be isomerized to /3-chlorocodide, available directly from the isomers of codeine. The corresponding derivatives of morphine have been prepared. Bromocodide and bromomorphide may be prepared in like manner but cannot be isomerized, and an iodocodide results from the treatment of a-chloro- or bromocodide with potassium iodide. 

Hydrogenation of a-chlorocodide hydrochloride in glacial acetic acid using a platinum oxide catalyst [19] affords 52 per cent. 6-chloro-dihydrocodide [v] (cf. the reduction of (/(-codeine without opening of the ether link under similar conditions [21]—see Chap. IV), 40 per cent. 

The first product of hydrolysis of a-chlorocodide to be clearly recognized was i/r-codeine [n, R = Me] [36], and following the isolation of isocodeine [18, 37] and allo- -codeine [18] from the hydrolysis of bromocodide (q.v.) all three isomers were obtained by the hydrolysis of a- and /3-chlorocodide with acetic acid, the proportions varying with the two isomeric chloro compounds thus ... 

Speyer and Krauss [70] claimed the production of an allo-i/i-chloro-codide from allo- -codeine and phosphorus pentachloride, but using thionyl chloride only a quantitative yield of the /3-isomer was obtained [10]. In the same way isocodeine is converted quantitatively to /S-chlorocodide [10]. 

Also analyzed acepromazine, aceteiminophen, acetophenazine, albuterol, aminophylline, amitriplyline, amobarbital, amoxapine, amphetamine, amylocaine, antipyiine, aprobar-bital, aspirin, atenolol, atropine, avermectin, barbital, benzocaine, benzoic add, benzotro-pine, benzphetamine, berberine, bibucaine, bromtizepan, brompheniramine, buprenor-phine, bu irone, butabarbital, butacaine, butethal, caffeine, carbamazepine, carbromal, chloramphenicol, chlordiazepoxide, chloroquine, chlorothiazide, chloro lenol, chlorphe-nesin, chlorpheniramine, chlorpromazine, chlorpropamide, chlortetracydine, cimetidine, dnchonidine, cinchonine, clenbuterol, clonazepam, clonixin, clorazepate, cocaine, codeine, colchicine, cortisone, coumarin, cydazocine, Qrclobenzaprine, cydothiazide, cyheptamide, cymarin, danazol, danthron, dapsone, debrisoquine, desipramine, dexamethasone, dex-... 

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