Codeine extraction from opium

Both morphine and codeine are valuable analgesics. Morphine is extracted from opium, the dried latex of the opium poppy, and codeine is usually obtained from morphine by semi-synthesis (see Box 6.2), since the amounts in opium are rather small. Thebaine is a valuable raw material for semi-synthesis of a wide range of morphine-like drugs. 

Preparation Codeine is extracted from opium (present in... 

Codeine is extracted from opium. Opium is a chemically complex drug derived from a flowering plant, the opium poppy. The scientific name for the opium poppy is Papaver somniferum, which translated from Greek means poppy that causes sleep. Opium is produced by drying the thick liquid harvested from the unripe seed capsule of the flower. It contains several different medically important chemicals known as alkaloids (non-acidic chemicals), the most important being morphine and codeine. 

Codeine was extracted from opium in 1832, and was the first partial success in the attempt to discover a safer and less addictive drug. However, with fewer side effects came a less potent analgesic. About 100 mg of codeine are needed to produce the same effect as 10 mg of morphine. It was believed at the time (and it is still debated) that codeine s milder effects on a per weight basis actually result in fewer side effects when equally effective dosages are given (i.e., 100 mg of codeine produces fewer side effects than 10 mg of morphine). For the most part, standard medical practice has been to prescribe codeine for moderate pain, and reserve morphine for more severe pain. 

Codeine is a compound that is extracted from opium. It is used for pain relief. The pH of a 0.020 mol/L solution of codeine is 10.26. Is codeine an acid or a base Is it strong or weak Explain how you decided. 

The oripavines are made from an alkaloid which we have not described so far— thebaine (Fig. 12.26). Thebaine can be extracted from opium along with codeine and... 

Thebaine is present in opium at 0.3-1.5%. It is extracted from opium or from latex of the plant Papaver bracteatum, in which it is present at up to 26%. It is used to produce codeine. 

Even today, codeine is occasionally obtained by extraction from opium, although mostly by methylation of (-)-morphine. This methylation can be carried out selectively in a phase- transfer reaction with trimethylphenylammonium... 

Morphine (5) and codeine (methylmorphine) (6), two major morphinan-type alkaloids with an isoqninoline skeleton, are extracted from opium, the dried milky sap released from the immature finits of poppies (Papaver somniferum). Morphine and codeine can interact with opioid receptors distribnted in brain tissnes and the periphery, and are most widely nsed as narcotic analgesics, with codeine also having an antitussive effect [4, 25, 32]. 

The processes used in the manufacture of morphine are believed to be still based on that described by the Scottish chemist Gregory,in 1833, with improvements devised by Anderson. A description has been published by Schwyzer, who also deals with the manufactme of codeine, narcotine, cotarnine, and the commercially important morphine derivatives, diamorphine (diacetylmorphine), and ethylmorphine (morphine ethyl ether). More recently Barbier has given an account of processes, based on long experience in the preparation of alkaloids from opium. Kanewskaja has described a process for morphine, narcotine, codeine, thebaine and papaverine, and the same bases are dealt with by Chemnitius, with the addition of narceine, by Busse and Busse, and by Dott. It is of interest to note that a number of processes for the extraction and separation of opium alkaloids have been protected by patent in Soviet Russia. ... 

Papaverine, C20H21O4N. This alkaloid, first obtained by Merck, occurs in the mixture precipitated by ammonia from the mother liquors of opium extract from which morphine and codeine have been separated in Gregory s process, and methods for its isolation from this mixture have been published by Hesse and others. The alkaloid may be purified by conversion into the acid oxalate, B. H2C2O4, m.p. 196° or 201-5-202°, which is nearly insoluble in alcohol. 

Neopine, C gHaiOgN. This alkaloid was discovered by T. and H. Smith in the final mother liquors obtained in the extraction of opium alkaloids, and was examined by Dobbie and Lauder, and later by van Duin, Robinson and Smith, who cystallised the base, found it isomeric with codeine and showed that it is jS-codeine (p. 251). The base crystallises from light petroleum in needles, m.p. 127-127-5°. In aqueous solution... 

Opium The extract from Papaver somniferum containing morphine and codeine. 

Morphine (10) and codeine (11), constituents of opium, are the most interesting alkaloids found in nature. Morphine is also the oldest alkaloid isolated, in 1805, by the German pharmacist Sertiimer from opium, the sun dried latex of Papaver somniferum. The structure of morphine with its so-called morphinan skeleton, once called the acrobat under the alkaloids, was finally elucidated in 1952 by the first total synthesis performed by Gates and Tschudi. Many syntheses would follow [26], but all morphine used today, whether legal or illicit, originates in the natural source P. somniferum or its extract, opium. The latex may contain up to 20% morphine. Most legal morphine is converted into the anticough medicine codeine (Table 5.1) by treatment with trimethylanilinium methoxide, whereas almost all illicit morphine is acetylated to the diacetate heroin. 

Morphine and cocaine Morphine is medically the most important alkaloid present in opium. Opium itself consists of the dried milky exudate extracted from unripe capsules of the opium poppy (Papaver somniferum), which is grown mainly in Asia, but also in some parts of India and China. Morphine is a powerful analgesic and has been used to treat severe pain. However, its addictive properties complicate its long-term medical use and it is also a drug of abuse. In addition to morphine, opium also contains codeine, which has similar, but weaker, actions. 

The assumption which is made in the type of test deseribed following is that the related unknown substances will produce a similar intensity of spot to the test substance itself at equal concentrations. For example, a limit test is conducted for related (foreign) alkaloids in codeine, which is extracted from the opium poppy in which a range of alkaloids occur thus, the exaet identity of the impurities may not be known. To conduct the test, 10 pi amounts of three solutions are applied separately to a TLC plate. The solutions contain 4.0% w/v codeine (Solution 1),... 

Like morphine, codeine is extracted from natural opium, obtained from the poppy plant (Papaver somniferum). Only when it was first discovered and tested was codeine purified directly from opium (see Chapter 1). Today pharmaceutical-grade codeine is synthesized from morphine through the relatively simple chemical modification process of methylation, whereby CHj replaces a hydrogen atom on the morphine molecule. The chemical substitution reaction that takes place (H for CHj) does so at a specific location on the morphine molecule (Figure 3.1) if the substitution were to occur elsewhere on... 

Codeine, also known as methylmorpliine, C H2 NOt H20, is a colorless white crystalline substance, mp 154.9 C, slightly soluble in water, soluble in alcohol and chloroform, effloresces slowly in dry air. Codeine is derived from opium by extraction or by the methylation of morphine. For medical use, codeine is usually offered as the dichlotide, phosphate, or sulfate. Codeine is habit forming. Codeine is known to exacerbate urticaria (familiarly known as hives). Since codeine is incorporated in numerous prescription medicines for headache, heartburn, fatigue, coughing, and relief of aches and pains, persons with a history of urticaria should make this fact known to their physician. Codeine is sometimes used ill cases of acute pericarditis to relieve severe chest pains in early phases of disease. Codeine is sometimes used in drug therapy of renal (kidney) diseases. 

Opium alkaloids such as codeine, thebaine, papaverine, and noscapine exhibit high solubility (0.09-0.9 mg/g) in supercritical fluids including CO N,0, CHF, [37]. However, in spite of their high solubilities, they were not extracted from plant material by pure CO, to the degree expected [29], possibly because these alkaloids exist as their salt forms in plant tissue. In this chapter, the examples that show the difference of the solubilities between alkaloidal free bases and salts are presented. For this comparison, the solubilities of the free bases of hyoscyamine (1), scopolamine (2), pseudoephedrine (6) were measured and compared with those of their hydrochloride salts (Figures 3 and 4). 

The codeine that occurs naturally in small amounts in opium is isolated from the aqueous morphine alkaloid mother liquors by immiscible extraction with a nonaqueous solvent. Dilute sulfuric acid is employed to extract the codeine sulfate from the nonaqueous solvent. This solution is evaporated, crystallized, and recrystallized. The alkaloid is precipitated from a sulfate solution by alkali and purified, if necessary, by alcoholic crystallization. It is converted into the phosphate by solution in phosphoric acid, evaporation, crystallization, centrifugation, and drying. 

Codeine is the methylic ether of morphine (3-methylmorphine) and can be isolated from opium during the extraction of morphine, but is usually prepared by the methylation of morphine. Codeine is used in medicine as an antitussive drug and furthermore it has analgesic properties. It may cause addiction, but less than morphine. 

Codeine is extracted and isolated from opium. Mid-1800s The Opium Wars are fought between China... 

Opiates are compounds extracted from the milky latex contained in the unripe seed pods of the opium poppy (Papaver somniferum). Opium, morphine, and codeine are the most important opiate alkaloids found in the opium poppy. Opium was used as folk medicine for hundreds, perhaps thousands of years. In the seventeenth century opium smoking led to major addiction problems. In the first decade of the nineteenth century, morphine was isolated from opium. About 20 years later, codeine, one-fifth as strong as morphine, was isolated from both opium and morphine. In 1898, heroin, an extremely potent and addictive derivative of morphine was isolated. The invention of the hypodermic needle during the mid-nineteenth century allowed opiates to be delivered directly into the blood stream, which increases the effects of these drugs. Synthetically produced drugs with morphine-like properties are called opioids. The terms narcotic, opiate, and opioid are frequently used interchangeably. Some common synthetically produced opioids include meperidine (its trade name is Demerol) and methadone, a drug often used to treat heroin addiction. 

Natural opioids, that is, opioids extracted directly from opium include codeine—used for dental and other postoperative pain laudanum, paregoric—a mild tincture of opium mixed with camphor and used primarily for control of diarrhea and morphine. Heroin is a partial synthetic that combines morphine and diacetyl... 

Novoseven eptacogalfa factor VII. noscapine [ban, inn] (narcotine i-a-narcotine) is an alkaloid from Corydalis cava (Corydalis tuberosa), Papaver somniferum and other Papaver spp. It is a by-product in extraction of morphine from opium, and one of the first alkaloids to be isolated. It can be used as a centrally acting ANTITUSSIVE, similar in pharmacology to codeine, novobiocin [ban, inn] (Albamycin ) is an antibiotic with ANTIBACTERIAL activity against Gram-positive bacteria. It is also a LEUKOTRIENE RECEPTOR ANTAGONIST. 

Codeine may be isolated from opium by the Gregory process [9], in which the concentrated aqueous opium extract is treated with a concentrated solution of calcium chloride, when calcium meconate, lactate, and sulphate are precipitated and removed, when the filtrate on concentration deposits the Gregory salt , a mixture of the hydrochlorides of morphine and codeine. This is purified, dissolved in water, and the morphine precipitated by ammonia, when the codeine remains in solution from which it is extracted by benzene, or the solution concentrated to the point at which a mixture of codeine hydrochloride and ammonium chloride separates. Other procedures for the isolation of codeine are available [7, 8, 10-22 inc.], critical summaries of which are given by Kanewskaja [23] and Barbier [24], Codeine may be separated from neopine (see Chap. VII) through the sulphate [25] and from morphine by chromatography [26-29]. Most of the codeine used commercially is prepared by the methylation of morphine (see below). 

The concentrated aqueous extract of opium, diluted with an equal volume of water, is treated with ammonia and left for twenty-four hours, when all the narcotine and morphine are precipitated. The remaining alkaloids are extracted by benzene, from which thebaine and codeine are removed by dilute acetic acid and the former precipitated by the addition of sodium carbonate to the acetate solution [14]. 

Codeine is nsed in medicine for its narcotic analgesic action. It is used as a sedative in cough mixtures. Codeine occurs in opium from 0.7% to 2.5%. It is prepared from morphine by methylating the phenolic —OH group of the morphine. It is also obtained by extraction of opinm. 

The commercial preparation of morphine takes place from opium and from poppy straw at approximately equal proportions. [72] Since 1960, the production of thebeine has gained growing significance, due to an increased demand for semi-synthetic opiates. This is generated from opium like morphine, codeine and papaverine. The key step is removal of the crude morphine with tartaric acid. The various alkaloids are subsequently separated by fractional crystallisation and extraction (Fig. 5.53). 

In 1834, codeine was isolated from opium by Pierre Jean Robiquet (1780-1840). One year later, Pierre-Joseph Pelletier (1788-1842) and M. Thiboumery discovered thebaine (named after the ancient Egyptian city of Thebes). In 1848, at the University of Giessen, papaverine was extracted from poppy waste by Georg Merck (1825-1873), the son of Heinrich Emanuel Merck. In 1870, Augustus Matthiessen (1831-1870) and Charles R. A. Wright (1844-1894) recognised that codeine is the monomethyl ether of morphine. After the selective methylation of morphine for the preparation of codeine had failed, Felix Hoffmann (1868-1946) tried out in 1897 a selective acetylation, in analogy to the synthesis of aspirin from salicylic acid. [91]... 

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