Phenols

PHENOLS BY VANA JAGAN MOHAN RAO

1. PHENOLS BY VANA JAGAN MOHAN RAO M.S.Pharm, MED.CHEM NIPER-KOLKATA Asst.Professor, MIPER-KURNOOL Email: [email protected]

2. Phenols are molecules that have a hydroxyl group attached to the carbon atom of an aromatic ring. In phenol, hydroxy functional group is directly attached to the sp 2 hybridized carbon atom of the benzene ring. The interaction of six unhybridized 2pz orbitals of carbon atoms of the benzene ring leads to the formation of delocalized pi-electron clouds. The C-O-H bond angle in phenol is 109 . The carbon-oxygen bond length ( 136pm )

3. In phenol carbon-oxygen bond length is slightly less than that in methanol (142 pm). This is due to partial double bond character on account of the conjugation of unshared electron pair of oxygen with the aromatic ring. Similarly, In ethers , the four electron pairs, i.e ; the two bond pairs and two lone pairs of electrons around oxygen are arranged approximately in a tetrahedral arrangement. The C-O-C bond angle ( 111.7 in methoxy methane) is slightly greater than the tetrahedral angle ( 109 28 ) due to the repulsive C-O bond length ( 141 pm ) in ethers is almost the same as in alcohols ( 142 pm in methanol).

4. The acidity of phenols is due to its ability to lose hydrogen ion to form Phenoxide ions. In a phenol molecule, the sp 2 hybridised carbon atom of the benzene ring attached directly to the hydroxyl group acts as an electron-withdrawing group. This sp 2  hybridized carbon atom of a benzene ring attached directly to the hydroxyl group has higher electronegativity in comparison to the hydroxyl group. Due to the higher electronegativity of this carbon atom in comparison to the hydroxyl group attached, electron density decreases on the oxygen atom. The decrease in electron density increases the polarity of O-H bond and results in the increase in ionization of phenols. Thus , the phenoxide ion is formed. The phenoxide ion formed is stabilized by the delocalization of negative charge due to the resonance in the benzene ring. Phenoxide ion has greater stability than phenols, as in the case of phenol charge separation takes place during resonance. ACIDITY OF PHENOLS

5. The resonance structures of phenoxide ions explain the delocalization of negative charge. In the case of substituted phenols, the acidity of phenols increases in the presence of the electron-withdrawing group. This is due to the stability of the phenoxide ion generated. The acidity of phenols further increases if these groups are attached at ortho and para positions. This is due to the fact that the negative charge in phenoxide ion is mainly delocalized at ortho and para positions of the attached benzene ring. On the other hand, the acidity of phenols decreases in the presence of electron-donating groups as they prohibit the formation of phenoxide ion.

6. 1. From sulphonic acids (by alkali fusion of sodium benzene sulphonate ) The first commercial process for the synthesis of phenol. Sodium benzene sulphonate is fused with sodium hydroxide at 573K to produce sodium phenoxide, which upon acidification yields phenol. PREPARATION METHODS OF PHENOLS

7. 2. Preparation of Phenols from Haloarenes : Chlorobenzene is an example of haloarenes which is formed by the monosubstitution of the benzene ring. When chlorobenzene is fused with sodium hydroxide at 623K and 320 atm sodium phenoxide is produced. Finally, sodium phenoxide on acidification gives phenols.

8. 3. Preparation of Phenols from Benzene Sulphonic Acid: Benzenesulphonic acid can be obtained from benzene by reacting it with oleum . Benzenesulphonic acid thus formed is treated with molten sodium hydroxide at high temperature which leads to the formation of sodium phenoxide. Finally, sodium phenoxide on acidification gives phenols.

9. 4. Preparation of Phenols from Diazonium Salts: When an aromatic primary amine is treated with nitrous (NaNO2 + HCl) acid at 273 – 278 K, diazonium salts are obtained. These  diazonium salts are highly reactive in nature. Upon warming with water, these diazonium salts finally hydrolyze to phenols. Phenols can also be obtained from diazonium salts by treating it with dilute acids.

10. 5. Preparation of Phenols from Cumene: Cumene is an organic compound obtained by Friedel-Crafts alkylation of benzene with propylene. Upon oxidation of cumene ( isopropylbenzene ) in the presence of air, cumene hydroperoxide is obtained. Upon further treatment of cumene hydroperoxide with dilute acid, phenols are obtained. Acetone is also produced as one of the by-products of this reaction in large quantities. Hence, phenols prepared by these methods need purifications.

11. PHYSICAL PROPERTIES OF PHENOLS 1. Boiling Point of Phenols Phenols generally have higher boiling points in comparison to other hydrocarbons having equal molecular masses. This is due to the presence of intermolecular hydrogen bonding between hydroxyl groups of phenol molecules. In general, the boiling point of phenols increases with an increase in the number of carbon atoms.

12. 2. Solubility of Phenols The solubility of phenol in water is governed by the hydroxyl group present. The hydroxyl group in phenol is involved in the formation of intermolecular hydrogen bonding. Thus, hydrogen bonds are formed between water and phenol molecules which make phenol soluble in water. However, the aryl group attached to the hydroxyl group is hydrophobic in nature. Thus, the solubility of phenol decreases with the increase in the size of the aryl group . 3 . Chirality of Phenols Phenols exhibit chirality within their molecules, for example, catechin . This chirality is due to the absence of planar and axial symmetry in the phenol molecule.

13. CHEMICAL PROPERTIES OF PHENOLS 1.HALOGENATION:

14. 2. NITRATION: 3 . SULPHONATION:

15. 4. KOLBE’S REACTION:

16. QUALITATIVE TESTS OF PHENOL

17. T he following tests can be carried out to detect the phenolic functional group. a)Litmus test b)Ferric chloride test c) Libermann’s test d)Bromine water test e) Phthalein dye test (a) Litmus Test: Scientists use litmus paper to test whether the given solution is acidic or basic. Red litmus paper turns blue while blue litmus paper remains unchanged in the presence of a base. Phenol turns blue litmus paper red . This shows that phenol is acidic in nature. Carboxylic acid also give this test. Compare to carboxylic acid phenol is weakly acidic and it does not give an effervescence with aqueous sodium carbonate.

18. (b) Ferric Chloride Test: Aqueous solution of phenol reacts with freshly prepared ferric chloride solution gives coloured complex. Most phenols give dark coloured solution. The chemical reaction is given below. 6C 6 H 5 OH + FeCl 3  → [ Fe(C 6 H 5 O) 6 ] 3–   + 3HCl + 3H + ( violet colour complex) The colours produced by simple phenolic compounds with ferric chloride solution is listed below. Phenol, resorcinol, Ortho cresol, Para cresol Violet or blue colouration Catechol Green colouration Hydroquinone Violet or transient blue color Pyrogallol Blue rapidly changing to red

19. (c) Libermann’s Test: Phenol reacts with concentrated sulfuric acid and sodium nitrite forms a yellow colour quinone monoxime complex. With excess of phenol and sulfuric acid a deep blue indophenol complex is formed. On dilution a red colour indophenol is formed which turns to deep blue colour sodium salt solution of indophenol on treatment with sodium hydroxide. Note:  This test is given by phenols which contain a free para position.

20. (d) Bromine Water Test: Phenol undergoes electrophilic substitution reaction with bromine. When bromine water is added to aqueous solution of phenol the brown colour of bromine disappears and a white precipitate of tribromophenol is formed. The chemical reaction is given below .

21. (e) Phthalein Dye Test: Phenol on heating with phthalic anhydride in the presence of concentrated sulfuric acid forms a colourless condensation compound called phenolphthalein. On further reaction with dilute sodium hydroxide solution gives a pink colour fluorescent compound called fluorescein . Characteristic colours are produced by different phenolic compounds which can be viewed under white background . The colours produced by different phenolic compounds in phthalein dye test is listed below. Phenol Reddish pink o-cresol Red m-cresol blue or violet blue 1-naphthol green 2-naphthol faint green Resorcinol yellow-green fluorescence Hydroquinone deep purple

22. STRUCTURES AND USES AROMATIC ALCOHOLS

23. Uses of Phenol: It is used as a precursor in drugs It is used as an antiseptic It is used in the production of nylon It is used to preserve vaccines It is used in oral analgesics Derivatives of phenol are used in beauty products like hair color and sunscreen It is used in the synthesis of plastics It is used to produce detergents and carbonates STRUCTURE & USES OF PHENOL

24. STRUCTURE & USES OF CRESOL Uses of Cresols: Mixed cresols are used as disinfectants, preservatives, and wood preservatives. o -Cresol is used as a solvent, disinfectant, and chemical intermediate. m -Cresol is used to produce certain herbicides, as a precursor to the pyrethroid insecticides , to produce antioxidants and to manufacture the explosive, 2,4,6-nitro-m-cresol. p -Cresol is used largely in the formulation of antioxidants and in the fragrance and dye industries. Uses for various Drugs Synthesis: o -Cresol used for synthesis of Carvacrol . m -Cresol used for synthesis of Toliprolol , Tolamolol etc. p -Cresol is consumed mainly in the production of antioxidants, e.g., Butylated HydroxyToluene (BHT)

25. Resorcinol C 6 H 6 O 2 Molecular Weight of Resorcinol 110.1 g/mol Density of Resorcinol 1.28 g/cm 3 Boiling Point of Resorcinol 277 °C Melting Point of Resorcinol 110 °C Uses of Resorcinol : Resorcinol is used as a disinfectant or an antiseptic in pharmaceutical products. It is used to treat skin infections as seborrheic dermatitis, psoriasis, calluses, eczema, warts, and acne. It is used in the manufacturing of resins. It is an analytical reagent used to determine the quality of ketoses. STRUCTURE & USES OF RESORCINOL

26. STRUCTURE & USES OF NAPTHOLS Uses of Napthols : Naphthols (both 1 and 2 isomers) are used as biomarkers for livestock and humans exposed to polycyclic aromatic hydrocarbons 1-Naphthol is a precursor to a variety of insecticides including carbaryl and pharmaceuticals including nadolol. It undergoes azo coupling to give various azo dyes, but these are generally less useful than those derived from 2-naphthol. In Molisch's test , 1-naphthol dissolved in ethanol, known as Molisch's reagent, is used as reagent for detecting the presence of carbohydrates. The Sakaguchi test uses 1-naphthol with sodium hypobromite to detect the presence of arginine in proteins. The Voges–Proskauer Test uses 1-naphthol in potassium hydroxide (KOH) solution to detect the breakdown of glucose into acetone which is used by bacteria for external energy storage. A positive test will be indicated by the appearance of a red color of the original yellow solution.

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