Extraction of caffeine from tea leaves

Do you know that tea contains caffeine ? We tried following procedure in our lab to extract the caffeine content from tea leaves. Here is the procedure.

Boil 20g of dry leaves in 500ml beaker and 250ml water added to it and was boiled for 25minutes. The solution is filtered through a buchner funnel without using a filter paper. To the clear filtrate,with stirring 60ml of 10% lead anhydride was added to precipitate tannins (naturally occuring polymers). The mixture was left undisturbed for 2-3 days. After this period,the solution was filtered through a glass wool and the solution was concentrated on a sand bath to about 30ml. The solution was cooled and extracted it thrice with 25ml portions of chloroform. The chloroform extracts were combined and most of the chloroform was removed by distillation.

The residue was cooled and 40ml of petroleum ether is added and stirred for 5min. Now the crude caffeine was filtered.

Here the organic solvent chloroform is used to extract caffeine from aqueous extract. Because it is more soluble in chloroform then in water. Chloroform caffeine mixture can be separated on the basis of different densities of chloroform and water, because chloroform is much denser than water and insoluble in it.

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Skraup’s Synthesis

This reaction was first studied in 1880 by Zdenko Hans Skraup (1850-1910), a Czech scientist born in Prague city of Czech Republic. His other works were in the fields of natural products like the structure of alkaloids, synthesis of iso-quinolines etc. Skraup’s synthesis is a chemical reaction used to synthesize quinolines by the condensation of glycerine and alanine in the presence of a strong acid (c.H2SO4) and an oxidizing agent like nitrobenzene. Other examples of oxidizing agents used are As2O5 (Arsenic acid). Initially when the reaction was done, As2O3 was used as an oxidizing agent and the reac-tion was known as violet reaction. In the present day world, in this reaction, Nitrobenzene is used not only as an oxidi z-ing agent but also as a solvent.

The reaction in its essence is stated below:

                                       

The mechanism of the reaction still remained elusive, however, there is a good reason to believe that it proceeds via the formation of acrolein as the intermediate. Acrolein is obtained by the dehydration of glycerol in the presence of c.H2SO4. The steps in the mechanism are described below:

Step 1: Formation of acrolein by the action of H2SO4 on glycerine. Dehydration of glycerine results in the loss of two molecules of water ultimately resulting in the formation of acrolein.

            

Step 2: Action of Acrolein on Aniline forming the addition product and intramolecular electrophilic addition followed by protonation, dehydration and oxidation.

 

Some of the major applications of this reaction are listed below: 
(1). Skraup’s synthesis is used to produce the malarial drug 4,6-dimethylquinoline from p-toluidine and methyl-vinyl-ketone.

                             

(2). Benzoquinoline can be synthesized from α-Naphthylamine

                               

(3). 1,10-Phenanthroline can be synthesized from 8-Aminoquinoline. 

                               

(4). 1,5-Naphthylidine can be synthesized from 3-Aminopyridine.

                                

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Hofmann-Loeffler-Freytag reaction

Radicals are reactive species that usually and readily abstract a hydrogen atom from metal hydrides. In some cases, in particular with substrates that meet certain geometric requirements, intramolecular C-H abstraction can take place. In this way, a new radical can be generated at an unactivated position, thereby allowing the introduction of functional groups at this position. The geometrical requirements dictate that the most frequently observed intra-molecular hydrogen transfers are 1,5-shifts, corresponding to specific attack on a hydrogen atom attached to a C-atom 5 from the initial radical. As shown below in the general example, hemolytic cleavage of the Y-X bond gives a radical Y* (normally nitrogen or oxygen centered), which is followed by hydrogen atom transfer. The resulting (more stable) carbon radical reacts with a neutral molecule or with a radical X’* which may or may not be identical with X*

           

One such example is the Hofmann–Loffler–Freytag reaction, which provides a method for the synthesis of pyrrolidines from N-halogenated amines. The reaction is effected by warming a solution of the halogenated amine in strong acid (e.g. H2SO4 or CF3COOH), or by irradiation of the acid solution with ultra-violet light. The initial product of the reaction is the δ-halogenated amine, but this is not generally isolated, and by basification of the reaction mixture it is converted directly to the pyrrolidine (or its derivatives). Both N-bromo- and N-chloro-amines have been used as substrates, although the N-chloro-amines usually give slightly better yields. The N-chloro-amines can be obtained from the amines by the action of sodium hypochlorite or N-chlorosuccinimide.

        

Thermal or photochemical dissociation of the N-chloro-ammonium salt, formed by protonation of the N-chloro-amine, is thought to give the reactive ammonium radical species. This abstracts a suitably situated hydrogen atom to give the corresponding carbon radical. This in turn abstracts a chlorine atom from another molecule of the N-chloro-ammonium salt, thus propagating the chain and at the same time forming the δ-chloro amine, from which the cyclic amine is obtained.

The mechanism is shown below:

(1). The Initiation Steps:

        

(2). The propagation steps:

        

(3). The final work up steps:

        

The first example of this type of reaction was reported by Hofmann in 1883. In the course of a study of the reactions of N-bromo-amides and N-bromo-amines, he treated N-bromo-coniine with hot sulfuric acid and obtained, after basification, a tertiary base that was later identified as δ-coneceine. Further examples of the reaction were reported later by Loffler, including a synthesis of the alkaloid nicotine. Many other cyclizations leading to simple pyrrolidines and to more complex polycyclic structures have since been reported.

                                        

The radical nature of the reaction is supported by a number of factors, including the fact that the reaction does not proceed in the dark at room temperature and that it is initiated by heat, light or iron (II) salts and inhibited by oxygen. The hydrogen abstraction step must be intramolecular in order to explain the specificity of reaction at the δ-carbon atom.

As with other radical reactions, secondary hydrogen atoms react more readily than primary as the resulting secondary radical is more stable. Thus, in the example given below, in the reaction of N-chloro-amine, attack by the nitrogen-centred radical on the δ-methyl group would lead to N-pentylpyrrolidine, whereas attack on the δꞌ-methylene would result in the formation of N-butyl-2-methylpyrrolidine. Only the latter compound was formed. Tertiary hydrogen atoms react very readily, but the resulting tertiary halides do not normally proceed to give cyclic amine products.

                       

Some of the illustrative examples of Hofmann-Loeffler-Freytag reaction are shown below:

(1). An application of the Hofmann–Loffler–Freytag reaction is found in the synthesis of the steroidal alkaloid derivative dihydro-conessine which is as shown below. In this synthesis, the pyrrolidine ring is constructed by attack on the unactivated C-18 angular methyl group of the precursor by a suitably placed nitrogen radical. The ease of this reaction is a result of the fact that in the rigid steroid framework, the C-18 angular methyl group and C-20 side chain carrying the nitrogen radical are suitably disposed in space to allow easy formation of the six-membered transition state necessary for 1,5-hydrogen atom transfer.

                            

(2). When haloamines are the derivatives of primary amines, reaction takes place in the presence of Fe(II) as the initiator.

    

(3). With N-halocycloalkylamines cyclization leads to bridged ring structures, but in these cases products may not be exclusively pyrrolidine derivatives. In some cases, six membered bicyclic ring is formed instead of five membered heterocyclic ring. N-Bromo-N-methyl cycloheptylamine gives tropane. In this case pyrrolidine ring is formed.

                                           

References:
(1). Modern Methods of Organic synthesis by William Carruthers & Iain Coldham; Cambridge University Press.
(2). Photochemistry and Pericyclic Reactions by Jagdamba Singh and Jaya Singh; New Age International Publishers.
(3). M. E. Wolff, Chem. Rev., 63, 55 (1963); “Cyclization of N-Halogenated Amines (The Hofmann-Loffler Reaction)”

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