*9.4.1 Extraction of caffeine*

Caffeine is a natural product found in Coffee, cocoa beans, kola nuts, and tea leaves in a substantial amount. Its efficient extraction from Coffee relies heavily on the properties of caffeine and other components present in Coffee. One of the most popular species of the genus whose seeds contains caffeine is *Coffea arabica* (**Figure 12**). Several methods can be used to extract caffeine, including Ultrasonic extraction, Heat Reflux extraction, and Soxhlet extraction. Heat Reflux extraction is commonly used methods to extract caffeine from Coffee [116]. The initial solvent used in the extraction of caffeine is water. Caffeine is sparingly soluble in water at ambient temperature (2 g/100 mL) but increasing when mixed in boiled water (100°C) with a yield of 66 g/ 100 mL. Meanwhile, the solubility of caffeine in chloroform, toluene, acetone and ethyl acetate is relatively high at ambient temperature [116, 117]. Caffeine is a weakly basic, white colorless powder in its anhydrous state.

#### **Figure 11.**

*General procedure to obtain alkaloidal extracts from crude plant material [114].*

**Figure 12.** *Chemical structure and a few data of caffeine.*

There are several ways to remove caffeine from coffee. Here are few reported procedures:

## *9.4.1.1 Extraction procedure I: solvent extraction using dichloromethane (DCM)*

Coffee seeds are firstly grounded and refluxed in an aqueous sodium carbonate solution for about 20 minutes under constant stirring. After filtration of the resulted mixture to filtrate is allowed for cooling at room temperature. The DCM is use to perform the partition of the aqueous filtrate. The process is repeated several times to extract more caffeine. The DCM fractions are then mixed with anhydrous sodium sulfate to remove water traces, the DCM-caffeine solution is filtered through reverse-phase filter paper, which will trap any water and residual matter. The DCM solution is allowed to evaporate and the white amorphous powder of caffeine is obtained [118].

The addition of sodium carbonate converts the protonated form of caffeine, which is naturally present in coffee, to its free caffeine form. During the extraction of caffeine, tannins being soluble in water and organic solvents can interfere with extraction. A weak base such as calcium carbonate or sodium sulphate can be added to break down tannins esters bonds into glucose and calcium or sodium salts of gallic acid, both of which will not be extracted into the organic solvent.

#### *9.4.1.2 Extraction procedure II: supercritical carbon dioxide extraction*

Some benefits are reported when using this method: caffeine is easily extracted from the final product after avoiding the use of flammable and toxic solvents. In this process, caffeine diffuses into supercritical CO2 with water. Coffee beans are introduced at the top while fresh CO2 is introducing at the bottom of an extractor vessel in a continuous extraction to remove caffeine. The recovery is accomplished in a separate absorption chamber containing water. Higher temperature and pressure are mandatory to obtain great yields. A pretreatment step is needed in this process. The addition of polar cosolvents affects cosolvent solute specific chemical or physical interactions. The extraction rate is accelerated by the solvent–cosolvent interaction and makes the extraction easier. The material is humidified with ultrapure water for prewetting, this will destroy the hydrogen bonds that link the caffeine to its natural matrix. Cell membrane swelling enhances solute diffusion. Subsequently, the quality of caffeine extracted can reach a purity >94%, which is generally the standard criteria for use in the soft drink and drug companies [119].

#### *9.4.1.3 Extraction procedure III: activated charcoal*

There are some benefits to use charcoal: it is cheaper, "green," and ease to regenerate by heat and steam. The choice of active charcoal with the appropriate

#### *Extraction of Bioactive Compounds from Medicinal Plants and Herbs DOI: http://dx.doi.org/10.5772/intechopen.98602*

number of micropores and a specific area up to 1000 m2 /gram is mandatory for good absorption performance.

Cleaned green coffee beans are firstly soak in water, and the caffeine and other soluble content transferred to the aqueous phase. During the filtration through the activated charcoal, solely caffeine will continue to migrate in water. The recovered and dried coffee beans are now decaffeinated [30].

#### *9.4.2 Extraction of morphine*

The poppy straw (*Papaver somniferum* capsules) produces a white sticky latex known as opium. Usually, two weeks after the petals fall from the bud farmers harvest and collect opium. To allow the viscous latex to ooze out slowly farmers generally use sharp blade to do two to five incisions into the pod's skin. 24-hours after incisions of the pod, opium is then collected. This gummy latex, or opium (poppy tears), is a complex mixture containing at least 50 different alkaloids (**Figure 11**). Morphine is the major alkaloid, making up to 8–17% of the dry weight of opium. The chemical structure of morphine was established in 1925 despite de fact it has been used for centuries. Even if the immense majority of morphine continues to be harvested from the opium poppy, there are at least three classical processes (all old) for the extraction of morphine from simple starting material [120].

### *9.4.2.1 Extraction by Merck process*

Cold water is used to treat the opium and the obtained aqueous solution concentrated until syrupy consistence. Powered sodium carbonate is added to precipitate hot and heated as long as ammonia given off; it is recommended that the solution remain alkaline to phenolphthalein and left aside four 24 hours at room temperature. After standing, the precipitate is filtered and cold water is use to wash several times until the wash-water become colorless. The precipitate is dissolved in alcohol at 85°C and the alcoholic solution is allowed for evaporation until dryness, and the residue is exhausted after neutralization with little amount of acetic acid. Decolorizing charcoal is used to treat the acidic solution and afterward precipitated with ammonia, avoiding excess is important. After filtration, the precipitate is washed and purified by crystallization in alcohol; concentration of the alcoholic mother-liquor yields a further quantity of morphine. This procedure was reported to be impossible to be consider for industrial scale because of the slight solubility of morphine is alcohol [120].

#### *9.4.2.2 The Thiboumery and Mohr process*

The gummy opium in divide into thin slices and treated with hot water thrice of its weight until obtain a homogeneous paste. After filtration the residue is pressed and treated again with thrice its weight in water. The resulted solutions are combined and allowed to evaporation until half their volume and poured into boiling milk of lime. One part of lime in ten parts of water should be used for four parts of opium; it is then filtered off again. The lime solutions are united and concentrated to a quantity twice the weight of the opium used. The solution is filtered, heated to boiling, and morphine is precipitated by adding ammonium chloride. The solution is filtrated after cooling at room temperature, and the precipitate is washed, then purified by solution in hydrochloric acid and crystallization of the morphine hydrochloride. It is an attractive process since there are no technical difficulties and the morphine is well separated from the secondary alkaloids. The morphine solutions are relatively clean; however, the yield might be bad. The contributory factors may be the oxidation of morphine in alkaline solution, and the fact that the lime always retains morphine [120].

#### *9.4.2.3 The Roberson-Gregory process*

Five to ten times its weight of cold distilled water is used to completely exhaust the opium. The resultant solution is evaporated to the consistency of a soft extract. The process is repeated with cold distilled water. This aqueous re-extraction causes impurities to precipitate, they are filtered off and the solution obtained is evaporated until its density is 10° Baumé. For each kilogram of opium, one hundred and twenty grams of calcium chloride are added to the boiling liquor, which is further diluted with an amount of cold water equal to its volume. A mixture of a precipitate of meconate and sulfate of calcium is thus formed and is filtered off. After filtration, the filtrate is once more concentrated to produce a new deposit which consist almost entirely of calcium meconate. After removal of the residue by filtration, the filtrate is left to stand for few days until it becomes a crystalline mass called "Gregory's salt". It is a mixture of hydrochloride and codeine hydrochloride. The crystals obtained are drained and then placed in a cloth and squeezed out in the presser. Successive crystallization is employed and each time animal charcoal is used to decolorize the solutions. To separate morphine to codeine, sufficiently pure crystals are dissolve in water and ammonia is therefore added to precipitate morphine while codeine remains in aqueous solution.

The first disadvantage of this procedure is that 20 to 25% of the morphine is left with the secondary alkaloids in the brown and viscous mother-liquids after filtration of the Gregory's salt. The second drawback is that the hydrochloride of morphine and codeine crystallize in furry needles retains the mother-liquids in which the crystallization occurred. Several successive crystallization and subsequent recoveries are required for purification, which is a time-consuming process [120].

Later in 1957, an efficient method of extraction of morphine from poppy straw was developed by Mehltretter and Weakley. Water-saturated isobutanol containing 0.23% ammonia was used to extract morphine. Almost all the alkaloid was absorbed by passing off the raw opium through a cation exchange ions resin bed. Quantitative elution of morphine from the bed was achieved with dilute aqueous alkali. After neutralization and concentration, the crude morphine is obtained, and the eluate can be converted to hydrochloride pharmaceutical grade without difficulty. The general recovery of morphine was 90% [121].

Cooper and Nicola have reported recently a straightforward process for extraction of morphine with a good overall yield (**Figures 11** and **13**). Morphine and related alkaloids can be purified from opium resin and crude extracts by extraction in the following manner: first, soaking the resin with diluted sulfuric acid, which releases the alkaloids into solution. Either ammonium hydroxide or sodium carbonate then precipitates the alkaloids. The last step separates morphine from other opium alkaloids. Today, morphine is isolated from opium in relatively large quantities: over 1000 tons per year (**Figure 14**) [30].

Till date, morphine is used as a powerful painkiller to alleviate severe pain by acting straightaway on the brain. It also possesses euphoric and hallucinatory

*Extraction of Bioactive Compounds from Medicinal Plants and Herbs DOI: http://dx.doi.org/10.5772/intechopen.98602*

**Figure 14.** *Extraction protocol of morphine from raw opium by Cooper and Nicola [30].*

effects. Morphine can also be chemically converted by an acetylation reaction using acetic anhydride and pyridine to create a much more potent form of the narcotic drug known as heroin [30].
