Caffeine crystallization

In aqueous solution, caffeine associates to form at least a dimer and probably a polymer 12 the molecules are arranged in a stack.13 Caffeine will also associate with purines and pyrimidines either as the free bases or as their nucleosides.13 Caffeine crystallizes from water as a monohydrate [9],... 

The alkaloid caffeine is found in coffeef tea, and kola. It is also known less commonly by the name of theine, especially as found in tea. The amount present in coffee and tea is from 1-4.8 per cent in tea and 1-1.5 per cent in coffee. Caffeine crystallizes from water or alcohol, m.p. 234°. It is slightly soluble in water, less so in alcohol and ether and more in chloroform. It acts as a weak base. It may be prepared from either theobromine or from theophylline by further methylation, which confirms the constitution as the 1-3-7-tri-methyl product. 

Caffeine is about 10 times as soluble in hot water as in cold water. A chemist puts a hot-water extract of caffeine into an ice bath, and some caffeine crystallizes. Is the remaining solution saturated, unsaturated, or supersaturated ... 

A Cesaro, G Starec. Thermodynamic properties of caffeine crystal forms. J Phys Chem 54 1345-1346 (1980). 

C8H10N4O2. An alkaloid occurring in tea, coffee and guarana, from which it may be prepared by extraction, It is also manufactured by the methylation of theobromine and by the condensation of cyanoacetic acid with urea. Crystallizes with H2O or anhydrous from organic solvents. M.p. (anhydrous) 235"C, sublimes at 176 C. Odourless, and with a very bitter taste. Caffeine acts as a stimulant and diuretic, and is a constituent of cola drinks, tea and coffee. 

Legal nicotine, caffeine, alcohol, a number of sleeping tablets and tranquillizers. Illegal heroin, cocaine, crack, cannabis, amphetamine, crystal meth (methamphetamine). 

How would you describe the differences between a cup of coffee and a cup of hot water What probably come to mind are the aroma, the dark color, and the taste of a good cup of coffee. Coffee s action as a stimulant is another obvious difference. These properties come from the chemical compounds that hot water dissolves from ground coffee beans. These compounds are molecules constructed from different atoms bound together in veiy specific arrangements. The molecule that makes coffee a stimulant is caffeine. Our background photo is a magnification of crystals of pure caffeine, and the inset is a ball-and-stick model of this molecule. 

Chlorogenic acid forms a 1 1 complex with caffeine, which can be crystallized from aqueous alcohol and yields very little free caffeine on extraction with chloroform. Other compounds with which caffeine will complex in this way include isoeugenol, coumarin, indole-acetic acid, and anthocyanidin. The basis for this selection was the requirement for a substituted aromatic ring and a conjugated double bond in forming such a complex. This kind of complex does modify the physiological effects of caffeine.14 Complex formation will also increase the apparent aqueous solubility of caffeine in the presence of alkali benzoates, cinnamates, citrates, and salicylates.9... 

Also, hydrates are more soluble in water-miscible solvents than are the corresponding anhydrous forms. For example, the solubility of caffeine hydrate is lower than that of anhydrous caffeine in water but higher in ethanol. The maximum concentration seen may be due to the solubility of the anhydrous crystalline phase or due to a temporary steady state in which the rate of dissolution of the metastable anhydrous form and the rate of crystallization of the stable hydrate are equal. The decreasing concentration represents crystallization of the stable hydrate from a solution supersaturated with respect to it. If the maximum concentration of the solute in the dissolution experiment corresponds to the solubility, then the initial increase in concentration follows the Noyes-Whitney equation [15]. Van t Hoff plots of log solubility versus the reciprocal of temperature give linear relationships (Fig. 16). 

Solids that form specific crystal hydrates sorb small amounts of water to their external surface below a characteristic relative humidity, when initially dried to an anhydrous state. Below this characteristic relative humidity, these materials behave similarly to nonhydrates. Once the characteristic relative humidity is attained, addition of more water to the system will not result in a further increase in relative humidity. Rather, this water will be sorbed so that the anhydrate crystal will be converted to the hydrate. The strength of the water-solid interaction depends on the level of hydrogen bonding possible within the lattice [21,38]. In some hydrates (e.g., caffeine and theophylline) where hydrogen bonding is relatively weak, water molecules can aid in hydrate stabilization primarily due to their space-filling role [21,38]. 

Examples of solvent-mediated transformation monitoring include the conversion of anhydrous citric acid to the monohydrate form in water [235,236], CBZ with water [237] and ethanol-water mixtures [238,239], and cocrystallization studies of CBZ, caffeine, and theophylline with water [240]. Raman spectroscopy was used to monitor the crystallization rate and solute and solvent concentrations as griseofulvin was removed from an acetone solution using supercritical CO2 as an antisolvent [241]. Progesterone s crystallization profile was monitored as antisolvent was added [242]. 

The hydrogen bonding scheme is identical in both crystals as seen in Fig. 11 and Fig. 12. The molecules pack so as to provide what maybe aptly described as a hydrogen-bonded comb, with a GA 36 backbone and caffeine 35 teeth. In fact, the major difference between the two polymorphs on the secondary level of supramolecular architecture resides in the torsion of the GA 36 aliphatic chain. 

Fig. 11 Caffeine glutaric acid (35 36) form I crystal packing, showing two hydrogen-bonded combs [59]...

Stimulant drugs commonly abused in the USA include methamphetamine ("crank," "crystal"), methylenedioxymethamphetamine (MDMA, "ecstasy"), and cocaine ("crack") as well as pharmaceuticals such as pseudoephedrine (Sudafed) and ephedrine (as such and in the herbal agent Ma-huang) (see Chapter 32). Caffeine is often added to dietary supplements sold as "metabolic enhancers" or "fat-burners" and is also sometimes combined with pseudoephedrine in underground pills sold as amphetamine substitutes. 

If 0.01 mole of caffeine and 0.01 mole of pyrogallol are dissolved in 100 ml. of water at 60°C., a 1 1 crystalline complex will appear as the solution cools. Long needle-shaped crystals growing radially from central nuclei cause the entire solution to solidify into a gel-like structure with the fibrous appearance of mold (Figure 1). 

Figure I. Formation of caffeine-pyrogallol crystalline complex by cooling a saturated aqueous solution from above room temperature. Left, homogeneous solution, 0.1M in each component, above room temperature center, preliminary crystallization near room temperature right, gel-like structure of complex crystals after standing at room temperature for one day...

The electron density maps need further refinement, but the gross features are distinguishable. These maps show that caffeine and pyrogal-lol alternate in infinite columns parallel to the c axis of the crystal. This association could be characterized as a linear polymer held together by weak (compared with primary valence forces) intermolecular forces. 

A further method separates the extracted substances by absorption. Basic for this method is that there should be a high solubility of extracted substances in the absorption material, and that the solubility of absorption substance in the circulation solvent should be as low as possible. Further, the absorption material must not influence the extract in a negative way and a simple separation of extract and absorption material has to be available. An ideal absorption material is therefore a substance which is present in the raw material. Most plant-materials contain water, which can act as a very successful absorption material. An ideal example is the separation of caffeine for the decaffeination of coffee and tea. On the one hand, water has a low solubility in CO2, and on the other, water-saturated CO2 is necessary for the process. The extracted caffeine is dissolved into water in the separator and caffeine can be produced from this water-caffeine mixture by crystallization. One advantage of this separation method is that the whole process runs under nearly isobaric conditions. 

Caffeine, also known as theine, or methyltheobromine, 1,2,7-trimethyl xanthine (see structural formula in accompanying diagram), white, fleecy or long, flexible crystals. Caffeine effloresces in air and commences losing water at 80 C. Soluble in chloroform, slightly soluble in water and alcohol, very slightly soluble in ether, mp 236.8°C, odorless, bitter taste. Solutions are neutral to litmus paper. 

Table 5 Comparison of performance of quartz crystal microbalance chemosensors using molecularly imprinted polymer for determination of caffeine... 

Caffeine, the active substance responsible for the stimulant effect of the coffee plant s berry, is a methyl-xanthine, one of the family of stimulants present in more than 60 species of plants. The pure chemical forms white, bitter-tasting crystals, which were first isolated from coffee in 1820. Other family members are theophylline, found in tea leaves, and theobromine, found in the cacao pods that are ground to make chocolate. The most potent component in the coffee family by unit weight is theophylline, while theobromine, the weakest component by unit weight, stays in the body longer than does caffeine. 

Byrn SR, Lin C. The effect of crystal packing and defects on desolvation of hydrate crystals of caffeine and L-(-)-l,4-cyclohexadien-l-alanine. J Am Chem Soc 1976 98 4004-4005. 

In a study of the cocrystal systems formed by caffeine with formic acid, acetic acid, and trifluoroacetic acid, it was found that products prepared by means of solid-state grinding and solution crystallization were not... 

In a demonstration of the pharmaceutical advantage that can be realized through the use of a cocrystal form of a substance, it was shown that the 1 1 cocrystal of caffeine and methyl gallate exhibited significantly improved powder compaction properties [64], The compression characteristics of the cocrystal were reported to be excellent over the entire pressure range studied, with the tablet tensile strength of the cocrystal being twice that of caffeine at pressures less than 200 MPa. The superior compaction properties of the cocrystal product were attributed to the presence of slip planes in crystal structure. 

C.C. Sun, H. Hou, Improving mechanical properties of caffeine and methyl gallate crystals by cocrystallization, Cryst. Growth Des. 8 (2008) 1575-1579. 

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