Morphine Morpholine

Dibenz[h,e]azepine-6,11-diones ent-Morphinan nomenclature, 1, 29 Morphinan, 1,2,3,4-tetrahydro-nomenclature, 1, 29 14-a-Morphinan, N-methyl-synthesis, 1, 480 Morphinans nomenclature, 1, 29 as pharmaceuticals, 1, 148 synthesis, 2, 377 Morphine, 2, 512 as analgesic, 1, 167 as metabolite of normorphine, 1, 235 as pharmaceutical, 1, 146, 147, 148 synthesis, 1, 480 Morphine alkaloids structure, 4, 534 Morphin-7-en nomenclature, 1, 29 Morphinone, dihydro-as pharmaceutical, 1, 147 Morpholine — see also 1,4-Oxazine, tetrahydrocarcinogenicity, 1, 229 corrosion inhibitor, 1, 409 metabolism, 1, 226 nomenclature, 3, 996 structure, 2, 5 synthesis, 2, 89 Morpholine, 4-aciyloyl-polymers, 1, 291 Morpholine, alkenyl-polymers, 1, 291... 

This intramolecular etherification approach has successfully been applied to the syntheses136 of siccanin137 and clusifoliol,136 and a formal synthesis of morphine.138 Examples of tandem inter- and intramolecular etherification reactions have also been reported which convert catechol and o-aminophenol derivatives into benzodioxins (Equation (24)),139-141 benzodioxepines,142 and morpholines.139,140... 

The same type of reasoning allows production of pholcodine, an effective cough suppressant, from morphine. In this semi-synthesis, the electrophile is Ai-(chloroethyl)morpholine, and the leaving group is chloride. 

The above mentioned reactions are widely used in alkaloid modification. A good example of alkaloid modifications for clinical curation purposes are opioides. Morphine and codeine are natural products of Papaver somniferum. However, the codeine is naturally produced in small amounts. This is one reason why it is produced synthetically from morphine by modification. As codeine is the 3-0-methyl ether of morphine, the mono-O-methylation occurs in the acidic phenolic hydroxyl. Pholcodine is obtained by modification of morphine through alkylation with A-(chloroethyl)morpholine. Moreover, dihydrocodeine, hydro-morphone and heroine are also obtained from morphine through modifications. 

Hydrogenated derivatives of the monocyclic and bicyclic oxazines and thiazines are also very well established compounds and a number are so familiar that they too have trivial names. Tetrahydro-l,4-oxazine, for example, is better known as morpholine, a name first allocated to it because of a supposed, but erroneous, relationship to the alkaloid morphine. By analogy the corresponding thiazine is called thiomorpholine or sometimes thiazane. 

A modification of the WiUgcrodt reaction that simplifies the procedure by obviating the necessity of a sealed tube 01 autoclave consists in refluxing the ketone with a high-boiling amine and sulfur (Schwenk, 1942). Morpholine, so named because of a relationship to an early erroneous partial formula suggested for morphine, is suitable and is made technically by dehydration of diethanolamine. The reaction is conducted in the absence of water, and the reaction product is not the amide but the thioamide this, however, undergoes hydrolysis in the same manner to the arylacetic acid. 

The Knorr oxazine theory of morphine structure led to the preparation of a series of bases derived from morpholine [xxxm], so called on account of its supposed relationship to morphine [49-50]. In particular it was found that N-methylnaphthalanmorpholine [xxxrv] undergoes Hofmann degradation to a methine base [xxxv] that can be degraded further to naphthalene and /3-dimethylaminoethanol. The extraordinary ease with which this last stage takes place led Knorr to believe that an ort/to-attacbment of the nitrogen side-chain to the phenanthrene residue in the morphine alkaloids was improbable, and he accordingly advanced the structure [xxxvi] [51]). 

Monosaccharide, 972. See also Carbohydrates Monoterpene, 1026 Morphine, 869 Morpholine, 690... 

Methyl vinyl ketone, 177 Michael reactions, 129 Mimosamycin, 115, 116 Molecular sieves, 416, 486 Monochloroborane-Dimethyl sulfide, 354 Montmorillonite clay K-10, 507-508 Morphine, 102, 531 Morpholine, 459,486... 

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