Caffeine from Natural Sources

The process of destraction dates back to a discovery by Kurt Zosel (1913-1989) at the Max-Planck-Institut fur Kohlenforschung in Miilheim, who was engaged in normal-pressure polymerisation of ethylene. He had incidentally noticed, that residues from the distillation of oU, but also waste oil, vegetable fats and oils from natural products, could be extracted very well with supercritical gases. [514] This methodology offered correspondingly a number of other applications, as to extract hop aroma from hops, unsaturated fatty acids from fish oUs, vitamin E from vegetable oils, and paraffins or phenols from bituminous tar. 

198 Decaffeination of raw coffee at the pilot plant of the Max-Planck-lnstitut fur Kohlenforschung in Miilheim/ Ruhr. 

In 1895, Emil Fischer (1852-1919) published what was supposedly the first synthesis of caffeine. [515, 516] However, this was not the case, because the assumed structures of xanthine, theophylline [517] and caffeine were in fact wrong. He had believed, that they were 2,8-dioxopurines. 

The starting point for his synthesis was N,]SF-dimethylurea, the reaction of which with malonic acid gave N,N-dimethylbarbituric acid. With nitrous acid (sodium nitrite and a mineral acid) he produced dimethylvioluric acid, which gave dimethylpseudouric acid upon reduction and further reaction with potassium cyanate. Ring closure by heating with hydrochloric acid then led to 1,3-di-methyluric acid. [518] Its reaction with phosphorus pentachloride and reduction with hydrogen iodide then produced the supposed theophylline final 

The first correct synthesis of caffeine was achieved by Wilhelm Traube (1866-1942) in 1900. [519] In spite of some modifications that were introduced over the years, Traube s procedure stUl serves today as the basis for the industrial synthesis of caffeine, theobromine and theophyUine. 

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Caffeine and theobromine may be obtained in large quantities from natural sources, or they may be obtained by total or partial synthesis. Theophylline is usually produced by total synthesis. 

Caffeine is used medicinally as a CNS stimulant, usually combined with another therapeutic agent, as in compound analgesic preparations. Theobromine is of value as a diuretic and smooth muscle relaxant, but is not now routinely used. Theophylline is an important smooth muscle relaxant for relief of bronchospasm, and is frequently dispensed in slow-release formulations to reduce side-effects. It is also available as aminophylline (a more soluble preparation containing theophylline with ethylenediamine) and choline theophyllinate (theophylline and choline). The alkaloids may be isolated from natural sources, or obtained by total or partial synthesis. 

Many organic compounds are obtained from natural sources through extraction. This method takes advantage of the solubility characteristics of a particular organic substance with a given solvent. In the experiment here, caffeine is readily soluble in hot water and is thus separated from the tea leaves. Caffeine is one of the main substances that make up the water solution called tea. Besides being found in tea leaves, caffeine is present in coffee, kola nuts, and cocoa beans. As much as 5% by weight of the leaf material in tea plants consists of caffeine. 

Menthol from natural sources is obtained predominantly from the essential oil of corn mint Mentha arvensis), which is produced by steam distillation or a distdlation/extraction procedure using supercritical carbon dioxide cf. section 5.11 Caffeine). The menthol is frozen out and the crystalline mass centrifuged. Traces of impurities confer a slightly minty aroma to natural menthol. 

The worldwide demand for caffeine reaches almost 20,000 tonnes per annum. Approximately a quarter of this originates from natural sources the rest is obtained by chemical synthesis. The largest producer of synthetic caffeine is BASF, followed currently by the Chinese firms Shandong Xinhua Pharmaceutical, Jilin Shulan Synthetic, Shijiazhuang Pharmaceutical and Tianjin 23iongan. 

The wide and varied demand for caffeine has continually increased against a diminishing supply from natural sources. 

Caffeine (melting point 238°C, sublimes at 178°C density 1.23), theobromine, and theophylline are xanthine derivatives classified as central nervous stimulants, but differing markedly in their properties. They can be extracted from a number of natural sources. 

Methylxanthine is the major purine constituent of human urine (3.1 g in 1000 L). 3- and 7-Methylpurines are also minor constituents of urine, especially following large doses of caffeine or other methylated xanthines. 1,3-Dimethylxanthine (theophylline) occurs with caffeine in tea leaves and is a powerful diuretic. It has been used clinically in the treatment of asthma. The main purine constituent of the cocoa bean is 3,7-dimethylxanthine (theobromine). 1,2,7-Trimethylxanthine (caffeine) is the major purine of the coffee bean and also occurs in tea leaves (3.5%). It acts as a cardiac and respiratory stimulant. Caffeine can be extracted from the natural source by extraction with hot water. ... 

For the industrial production of caffeine, the Traube synthesis is stiU used. Around a quarter of pure caffeine results from extraction of natural sources e.g. by destraction of coffee with supercritical carbon dioxide). 

For experiments in which a compound is isolated from a particular source and is not prepared from other reagents, some information described in this section will not be applicable. Such experiments are called isolation experiments. A typical isolation experiment involves isolating a pure compound from a natural source. Examples include isolating caffeine from tea or isolating cinnamaldehyde from cinnamon. Although isolation experiments require somewhat different advance preparation, this advance study may include looking up physical constants for the compound isolated and outlining the isolation procedure. A detailed examination of the separation scheme is important here because it is the heart of such an experiment. 

Solvent extraction is a valuable method for obtaining a desired substance from its natural source. A familiar example is the hot-water extraction of caffeine (19) and the various oils that constitute the flavors of freshly brewed coffee and tea from coffee beans and tea leaves. As contrasted to the liquid-liquid extractions described in Section 5.2, this process is an example of solid-liquid extraction. The theory underlying it is the same, however. Because most organic compounds we wish to isolate are insoluble in water, organic solvents such as diethyl ether, dichloromethane, ethanol, and acetone are used for extracting natural products, that is, compounds found in nature. 

Obtain the IR spectrum of caffeine (use four scans with FT instruments). Compare your data with an authentic spectrum of caffeine and with the data given in Experiment [1 IB]. Your sample may be saved by taping it to a file card with your name, and stored by your instructor in a desiccator. If, later in the year, you isolate caffeine from its natural source (Experiment [IIB]), you will be able to compare the material you have extracted and purified from the plant with your own authentic reference spectrum. 

Purpose. To extract the active principle, an alkaloid, caffeine, from a native source, tea leaves. Caffeine is a metabolite (a product of the living system s biochemistry) found in a variety of plants. We wtU use ordinary tea bags as our source of raw material. This experiment illustrates an extraction technique often used to isolate water-soluble, weakly basic natural products from their biological source (see also Experiment [llA] for another extraction strategy). The isolation of caffeine win also give you the opportunity to use sublimation as a purification technique, since caffeine is a crystalline alkaloid that possesses sufficient vapor pressure to make it a good candidate for this procedure. In addition, the preparation of a derivative of caffeine, its 5-nitrosalicylate salt, will be carried out. This latter conversion takes advantage of the weakly basic character of this natural product. 

The kola nut, source of some of the flavoring of cola drinks, also has a bit of caffeine. About 5% of the 35 mg in a standard 9.5 oz (280 ml) serving of cola is naturally present from the kola nuts. The caffeine in sodas is added by the manufacturer. 

Caffeine is a bitter-tasting compound found in coffee, tea, cola beverages, and chocolate. Caffeine is a mild stimulant, usually imparting a feeling of alertness after consumption. It also increases heart rate, dilates airways, and stimulates the secretion of stomach acid. Caffeine is an alkaloid, a naturally occurring amine derived from a plant source. In Chapter 25 we learn about the properties and reactions of amines. 

These alkaloids can also be derived from nonaminoacid precursors. The N atom is inserted into the molecule at a relatively late stage, for example, in the case of steroidal or terpenoid skeletons. Certainly, the N atom ean also be donated by an amino acid source across a transamination reaction, if there is a suitable aldehyde or ketone. Pseudoalkaloids can be acetate and phenylalanine-derived or terpenoid, as well as steroidal alkaloids. Examples of pseudoalkaloids include such compounds as coniine, capsaicin, ephed-rine, solanidine, caffeine, theobromine, and pinidine (Figure 1.6). More examples appear in Table 1.1. Pseudoalkaloids can be as natural, biomimic, bionic, and synthetic alkaloids. 

The active ingredient that makes tea and coffee valuable to humans is caffeine. Caffeine is an alkaloid, a class of naturally occurring compounds containing nitrogen and having the properties of an organic amine base (alkaline, hence, alkaloid). Tea and coffee are not the only plant sources of caffeine. Others include kola nuts, mate leaves, guarana seeds, and, in small amount, cocoa beans. The pure alkaloid was first isolated from coffee in 1821 by the French chemist Pierre Jean Robiquet. 

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