Nicotine

Introduction to Nicotine

Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after the French ambassador in Portugal, Jean Nicot de Villemain, who sent tobacco and seeds to Paris in 1560, and who promoted their medicinal use. Nicotine was first isolated from the tobacco plant in 1828 by physician Wilhelm Heinrich Posselt and chemist Karl Ludwig Reimann of Germany, who considered it a poison. Its chemical empirical formula was described by Melsens in 1843, its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893, and it was first synthesized by Amé Pictet and A. Rotschy in 1904^.

Structure of Nicotine

The molecular formula for nicotine is C₁₀H₁₄N₂.

 

Nicotine is a hygroscopic, oily liquid that is miscible with water in its base form. As a nitrogenous base, nicotine forms salts with acids that are usually solid and water soluble. Nicotine easily penetrates the skin. As shown by the physical data, free base nicotine will burn at a temperature below its boiling point, and its vapors will combust at 308 K (35 °C; 95 °F) in air despite a low vapor pressure. Because of this, most of the nicotine is burned when a cigarette is smoked; however, enough is inhaled to cause pharmacological effects.

 

Biosynthesis

The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that compose nicotine. Metabolic studies show that the pyridine ring of nicotine is derived from nicotinic acid while the pyrrolidone is derived from N-methyl-Δ¹-pyrrollidium cation. Biosynthesis of the two component structures proceeds via two independent syntheses, the NAD pathway for nicotinic acid and the tropane pathway for N-methyl-Δ¹-pyrrollidium cation.

The NAD pathway in the genus nicotiana begins with the oxidation of aspartic acid into α-imino succinate by aspartate oxidase (AO). This is followed by a condensation with glyceraldehyde-3-phosphate and a cyclization catalyzed by quinolinate synthase (QS) to give quinolinic acid. Quinolinic acid then reacts with phosphoriboxyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase (QPT) to form nicotinic acid mononucleotide (NaMN). The reaction now proceeds via the NAD salvage cycle to produce nicotinic acid via the conversion of nicotinamide by the enzyme nicotinamidase.

The N-methyl-Δ¹-pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane-derived alkaloids. Biosynthesis begins with decarboxylation of ornithine by ornithine decarboxylase (ODC) to produce putrescine. Putrescine is then converted into N-methyl putrescine via methylation by SAM catalyzed by putrescine N-methyltransferase (PMT). N-methylputrescine then undergoes deamination into 4-methylaminobutanal by the N-methylputrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize into N-methyl-Δ¹-pyrrollidium cation.

The final step in the synthesis of nicotine is the coupling between N-methyl-Δ¹-pyrrollidium cation and nicotinic acid. Although studies conclude some form of coupling between the two component structures, the definite process and mechanism remains undetermined. The current agreed theory involves the conversion of nicotinic acid into 2,5-dihydropyridine through 3,6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate would then react with N-methyl-Δ¹-pyrrollidium cation to form enantiomerically pure (–)-nicotine.

Isolation of Nicotine

Nicotine, (S)­-3­-(1­-methyl­-2­-pyrrolidinyl) pyridine, is the most abundant of the volatile alkaloids in the tobacco leaf. The primary commercial source of nicotine is by extraction from the plant Nicotinia tabacum and Nicotinia rustica. Nicotine acts on nicotinic cholinergic receptors, affects most organ systems in the body and is a highly addictive drug. Nicotine normally makes up about 5 percent of a tobacco plant, by weight. Cigarettes contain 8 to 20 milligrams (mg) of nicotine (depending on the brand), but only approximately 1 mg is actually absorbed in the human body.

Procedure:

1. Weigh 10 g of cigarettes leaves in beaker.
2. Add 100ml NaOH solution and stir very well for 15 min. 
3. Filter in Buchner using glass wool and press the cigarettes very well by using other beaker. 
4. Transfer the cigarettes again to beaker. 
5. Add 30ml DW and stir and filter again. 
6. Collect the filtrate together. (If there is any impurities re-filter). 
7. Transfer the filtrate to the SF and extract by 25ml ether. 
8. Repeat the extraction 3times. 
9. Gather the 4 filtrates in conical flask. 
10. Dry by using 1teaspoon anhydrous potassium carbonate. 
11. Filter. 
12. Evaporate ether on water bath.(Avoid extra heat because nicotine is hydrolyzed by extreme heating).
13. After evaporation of ether add 4ml methanol to dissolve the resulted oil. 
14. Add 10ml saturated picric acid solution. 
15. Cool in an ice bath to precipitate the  nicotine di picrate crystals. 
16. Filter; allow drying and weighing the product.