phenol và tổng hợp phenol

CHAPTER Phenols 4.1 INTRODUCTION Phenols are the compounds containing a hydroxyl group (—OH) directly attached to an aromatic ring The term phenol is commonly used in the context of hydroxybenzene, which is a liquid at room temperature when contaminated with a little water It is the carbolic acid of pharmacy It was the first chemical to be used as an antiseptic as early as 1867 (Lister) It is being used as an important raw material in the manufacture of synthetic polymers (plastics) A number of phenols and phenolic ethers occur in nature Salicylic acid, for example, occurs in willow tree Some other important salicylic acid derivatives are methyl salicylate or oil of wintergreen —a common ingradient of liniments, and acetylsalicylic acid (aspirin)—a time honoured analgesic and antipyretic drug Thymol is a typical flavouring ingredient of thyme and is widely used in the preparation of mouthwash because of its flavour and antiseptic property Clove oil, used by dentists as an antiseptic, also contains a phenol, eugenol In addition, certain phenolic compounds are known for their specific physiological actions For instance, poison ivy (irritants) are 1,2-dihydroxybenzene derivatives having a long side-chain at 3-position A complex phenolic compound, tetrahydrocannabinol, is one of the active principles of the intoxicant marijuana OH OH OH COOH Phenol (Carbolic acid) OCOCH3 Salicylic acid (a phenol and an acid) CH3 COOH3 Methyl salicylate (a phenolic ester) OH OCH3 COOH Acetylsalicylic acid (Aspirin) OH CH(CH3)2 Eugenol 146 CH2CH Thymol CH2 PHENOLS 147 CH3 OH OH OH OCH3 OH H O C15 side chain Poison ivy irritants n-C5H11 CHO Vanillin CH3 CH3 (–)-Tetrahydrocannabinol CLASSIFICATION AND NOMENCLATURE We have mentioned above that phenols are hydroxy derivatives of aromatic (benzenoid) compounds They are represented by the general formula Ar—OH Depending upon the number of hydroxy groups, they are classified as monohydric (one—OH group), dihydric (two—OH groups), trihydric (three—OH groups) and polyhydric (more than three—OH groups) phenols Following two systems are in use for naming these compounds: (i) Common system: A number of phenols are assigned special names, while others are named as derivatives of these substances Compounds having only one additional substituent are named as the derivatives of phenol, the position of this substituent is indicated by letters o-, m-, or p- Some examples are given below: Monohydric phenols OH OH OH OH CH3 CH3 CH3 Phenol o-Cresol p-Cresol m-Cresol Dihydric phenols OH OH OH OH OH OH Catechol Resorcinol Quinol (Hydroquinone) Trihydric phenols OH OH OH HO OH Phloroglucinol OH Pyrogallol Chapter 4.2 H 148 ORGANIC CHEMISTRY [VOL-II] (ii) IUPAC system: In this system the simplest phenol is called benzenol But all substituted phenols are named as derivatives of phenol The carbon atoms of the aromatic ring are numbered commencing with the carbon atom bearing the root functionality (the —OH groups), the ring carbons are numbered successively so that the sum of numbers used to designate the position of substituents is minimum Following examples are illustrative (common names in parentheses) OH OH OH OH CH3 CH3 Benzenol (Phenol ) 2-Methylphenol (o-Cresol) NH2 3-Methylphenol (m-Cresol) 3-Aminophenol (m-Aminophenol) Dihydric, trihydric and polyhydric phenols are named as benzenediols, benzenetriols and benzenepolyols, respectively These names are also written as hydroxy derivatives of benzene However, they are better known by their trivial names parentheses For instance, OH OH 1 OH OH 1, 2-Benzenediol or 1, 2-Dihydroxybenzene (Catechol ) OH HO 1, 3-Benzenediol or 1, 3-Dihydroxybenzene (Resorcinol) OH 1, 3, 5-Benzenetriol or 1, 3, 5-Trihydroxybenzene (Phloroglucinol) OH OH OH 2 HO 3 OH 1,2,3-Benzenetriol or 1,2,3-Trihydroxybenzene (Pyrogallol) OH 1,2,4-Benzenetriol or 1,2,4-Trihydroxybenzene (Hydroxyquinol) Phenols with other substituents OH OH Cl NO2 Cl Cl 2, 4-Dichlorophenol 4-Chloro-2-nitrophenol However, when a functional group such as carboxylic group, ester or carbonyl group is present in addition to phenolic group, the phenols are named as hydroxy derivatives of these compounds The common names of these compounds are retained as root names The ring is numbered commencing with the designated functional group and going round successively as above Thus, PHENOLS 149 CHO Cl CHO OH OH OH 5-Chloro-2, 4-dihydroxybenzaldehyde 4-Hydroxy-2-nitrobenzaldehyde COOH COOC2H5 OH 4 OH Cl OH 2, 4-Dihydroxybenzoic acid (β-Resorcylic acid) 4.3 NO2 4 Ethyl 2-chloro-4-hydroxybenzoate STRUCTURE AND BONDING sp sp sp H 1s O sp 3-1s sp sp sp2 –sp3 C O, σ - bond H O 136 pm 109° Fig 4.1: Structure of phenol Due to higher electronegativity of oxygen atom, phenol molecule is dipolar in nature with the oxygen carrying partial negative charge Due to this dipolar nature phenols form hydrogen bonds It is noteworthy that the dipole moment of phenol (1.54D) is smaller than that of methanol (1.71D), because the C—O bond in phenol is less polar due to electron-withdrawing effect of the benzene ring while in methanol, C—O bond is more polar due to electron-donating effect of methyl group The phenol molecule cannot be depicted by any single valence bond structure In fact, it is considered as a hybrid of the following contributing forms: Chapter In phenols, the C—O bond is formed by the overlap of sp -orbital of carbon of benzene ring with a sp -orbital of oxygen atom while the O—H bond is formed by the overlap of second sp -orbital of oxygen with 1s orbital of hydrogen (Fig 4.1) The remaining two non-bonding sp3-orbitals of oxygen atom contain lone-pairs of electrons 150 ORGANIC CHEMISTRY [VOL-II] H + O H + O H H + O O OH – – – I III II IV V Resonating structures of phenol A perusal of the contributing forms II, III and IV clearly shows that the oxygen atom acquires a positive charge due to resonance This polarity facilitates release of proton and formation of phenoxide ion which is also stabilized by resonance – O O O O O – – – – Hydrogen bonding in phenols (i) Intermolecular hydrogen bonding: Like other compounds having —OH groups phenols either solids or liquids, exhibit intermolecular hydrogen bonding Due to these hydrogen bonds they exist as polymeric aggregates held together These aggregates break up on dilution with a non-polar solvent first into trimers or dimers and finally into the monomers on large dilution H H O H O H O H O O It has been observed that the boiling point of phenol is higher as compared to toluene (having comparable mol weight) This is due to the formation of intermolecular hydrogen bonding which results in the formation of polymeric aggregate where molecular mass increases many fold, thereby raising its boiling point The reason for the high boiling point may be due to the fact that additional energy is required to break the hydrogen bonds Toluene, on the other hand, does not form hydrogen bonds Phenol is somewhat soluble in water because it forms cross-intermolecular hydrogen bonding with water molecules, as shown below: H O H O H H O H O H H O H O H (ii) Intramolecular hydrogen bonding: A phenol, in which a carbonyl or a nitro group is attached at the ortho position, usually forms intramolecular hydrogen bonding as shown below: PHENOLS 151 CH3 O C N O O + O H O – H Intramolecular hydrogen bonding in o-Hydroxyacetophenone and o-Nitrophenol This type of hydrogen bonding also alters the physical and chemical properties of these molecules 4.4 METHODS OF FORMATION (i) From coal-tar: The middle oil fraction (443–513K) of coal-tar consists of phenol and cresols in addition to other compounds This fraction is collected and treated with alkali The alkaline layer is separated and carbon dioxide gas is bubbled through it The phenolic mixture that separates out is subjected to fractional distillation in order to isolate individual phenols (ii) From halobenzenes (Dow process): Chlorine in chlorobenzene is inert to nucleophilic displacement under usual conditions However, when chlorobenzene is heated with sodium hydroxide at 613K under pressure it forms phenol This method is used for commercial production of phenol and was first developed by Dow chemicals, USA in 1928 OH Chapter Cl – OH, 613K Pressure (320atm) Mechanism: This transformation takes place via benzyne mechanism as shown below: Cl 8%NaOH 613K, 320atm OH H – H – + OH – OH OH – –OH NaOH ONa –H2O However, if halobenzene has a strong electron-withdrawing substituent at ortho- or para-position, the hydrolysis of these compounds becomes easier Thus, 2,4-dinitrophenol and 2,4,6-trinitrophenol (picric acid) are obtained from the corresponding aryl halides using milder conditions Cl NO2 15% NaOH 433K O2N Cl NO2 HO O2N NO2 Aq Na 2CO 403K HO NO2 152 ORGANIC CHEMISTRY [VOL-II] O2 N O2 N NO2 Cl H2O NO2 HO 333K O2N O2 N 2,4,6-Trinitrochlorobenzene (Picryl chloride) 2,4,6-Trinitrophenol (Picric acid) (iii) From isopropylbenzene (cumene): This procedure is essentially used for the preparation of the parent compound, phenol Cumene (A) on catalytic aerial oxidation gives phenol via cumene hydroperoxide (B) CH3 CH3 C H5 C O2 Catalyst H C H5 C O CH3 CH3 (A) (B) O – CH 3COCH H C6H5OH Phenol This reaction, which is an example of autooxidation, is carried out at 423K in presence of hydrogen bromide as a catalyst It takes place by a free radical chain mechanism and is initiated by the abstraction of hydrogen from hydrocarbon by a bromine radical, which is produced by aerial oxidation of H—Br The free hydrocarbon radical thus produced picks up a molecule of oxygen forming peroxy radical which in turn abstracts hydrogen atom from H—Br in the propagation step to give cumyl hydroperoxide Initiation H Br + O2 Br + HOO Hydroperoxide radical CH3 C6H5 CH3 C H + Br C6H5 CH3 C + HBr CH3 Propagation CH3 CH3 C + O2 C6H5 C6H5 C CH3 C CH3 O CH3 CH3 C6H5 O CH3 O O + HBr C6H5 C CH3 O OH + Br PHENOLS 153 The cumyl hydroperoxide so obtained is treated with acid to form phenol The reaction is called cumyl hydroperoxide rearrangement CH3 + C6H5 C O H OH C6H5OH + CH3 CO CH3 CH3 The mechanistic path of this rearrangement involves initial protonation of the —OH group of hydroperoxide The resulting oxonium ion loses water to form a species with electron-deficient oxygen A carbocation, generated by phenyl migration, is stabilized by resonance Nucleophilic attack of water on this carbocation gives a hemilketal which undergoes acid-catalysed split to form the products CH3 CH3 C O O H + + + H C6H5 CH3 O OH2 CH3 CH3 + C6H5 C O C CH3 1, 2-Phenyl shift C6H5 CH3 C O + CH3 + C6H5 O C CH3 + OH2 H2 O CH3 C6H5 + OH C6H5 O C CH3 CH3 O C CH3 CH3 CH3 + H (A hemiketal) C6H5 O –H H + CO C6H5 O H O C CH3 H CH3 + + –H CH3 (iv) From diazonium salts: Addition of diazonium salt solution to a large excess of warm 50% sulphuric acid at 323K results in the formation of phenol + Ar N – NX + H2O + H 323 K Ar OH + N2 + HX Chapter C6H5 154 ORGANIC CHEMISTRY [VOL-II] (v) From sulphonic acids: Fusion of the alkali metal salt of an aromatic sulphonic acid with sodium or potassium hydroxide (solid) affords the corresponding phenol – + ArSO3Na + NaOH fuse (573 K) –Na2SO – ArO + +H ArOH Phenoxide This reaction is of general utility However, the hydrolysis of diazonium salt solution is a preferable procedure as the fusion carried out at higher temperatures leads to undesired side products 4.5 PHYSICAL PROPERTIES Various physical parameters such as boiling points, melting points, water solubilities and Ka values of some phenols listed in Table 4.1, are discussed below: (i) Physical state: A look at the Table reveals that most of the simpler monohydric phenols are either liquids or low melting solids Pure phenols are colourless but they usually turn reddish brown due to atmospheric oxidation (ii) Melting and boiling points: Nitrophenols, aminophenols and phenols having more than one hydroxyl group have relatively higher melting and boiling points This is probably due to the increased polar character resulting in higher degree of association involving intermolecular hydrogen bonding In general phenols are more polar than cycloalkanols having similar carbon skeletons This difference in polarities is reflected in higher melting and boiling points of phenol (m.p 316K; b.p 454K) as compared to those of cyclohexanol (m.p 298K; b.p 434K) Table 4.1: Physical Properties of Some Phenols Name phenol o-cresol m-cresol p-cresol o-fluorophenol m-fluorophenol p-fluorophenol o-aminophenol m-aminophenol p-aminophenol o-nitrophenol m-nitrophenol p-nitrophenol 2, 4-dinitrophenol 2, 4, 6-trinitrophenol catechol resorcinol m.p (K) 316 303.5 284 309 289.1 287 321 447 396 459 318 369 387 386 395 377 383 b.p (K) 454 463 473 474 425 451 459 — — — 490 — — — — — — Ka(H2O) at 298 Water solubility × 10–10 g/100g of H2O 1.3 0.63 0.9 0.62 1.5 5.2 1.1 2.0 69 — 600 50 690 1000000 very large 1.0 3.0 9.3 2.5 2.6 2.4 — — — 1.7 2.6 1.0 0.26 1.45 1.72 1.6 1.4 1.45 123 PHENOLS 155 hydroquinone pyrogallol 1, 2, 4-trihydroxybenzene phloroglucinol 446 406 413 490 — — — — 2.0 1.0 3.0 — 62 1.1 — (iii) Solubility: The solubility of phenol (m.w – 94, 9.3 g/100 g of H2O) is more than that of the cyclohexanol (m w – 100, 3.6 g/100 g of H2O) This difference can be attributed to the fact that the δ– δ+ phenolic —OH group is more polarized (as —O —H ) than alcoholic —OH group because of the resonance involving benzene ring in the case of the former Further, among the isomeric fluoro- and nitrophenols, the ortho isomers have lower melting points, boiling points and water solubilities and are weaker acids than the corresponding meta and para-isomers This is due to intramolecular hydrogen bonding in the case of ortho isomers and intermolecular hydrogen bonding in the case of meta- and para-isomers O O H – H o-Nitrophenol (Intramolecular hydrogen bonding) 4.6 O N + O – H O N O – + p-Nitrophenol (Intermolecular hydrogen bonding) SPECTRAL CHARACTERISTICS (i) Infrared spectra: Like alcohols the infrared spectra of phenols are characterized by the typical band in the 3600–3200 cm–1 region due to O—H stretching vibrations This band, however, shifts to 3610 cm–1 on dilution, due to the ‘free’ O—H group Further, the O—H stretching vibrations of those phenols which are capable of forming intramolecular hydrogen bonding appear in the 3200–2500 cm–1 region The phenols are distinguished from alcohols because of different frequencies of C—O stretching vibrations which show up at 1230 cm–1 in the former (Fig 4.2) The other characteristics of the infrared spectra are the typical absorption bands as expected from benzene derivatives μm 2.5 15 OH 3040 1465 1580 3340 4000 1492 cm–1 Fig 4.2: The IR spectrum of phenol 1230 800 Chapter O O O N 174 ORGANIC CHEMISTRY [VOL-II] OH OH OH COOH (i) NaOH, 340K (ii) H O + + CCl4 + Salicylic acid (Major product) COOH p-Hydroxybenzoic acid (Minor product) Mechanism: The mechanism of this reaction involves electrophilic substitution on the phenoxide by dichlorocarbene (I) which in turn is produced by 1,1-ElcB reaction of chloroform The resulting benzal derivative (II) undergoes alkaline hydrolysis to produce the corresponding aldehyde – OH + H CCl3 Fast – – H2O + CCl3; Cl2C Slow Cl – + Cl CCl2 Dichlorocarbene (I) – O O O H CHCl2 + –H + +H – + CCl2 – CCl2 II O – H O Cl C Cl – O Cl C – –Cl O – OH CHO – –Cl –H2O H – – II H CHO + H3O + OH + OH The predominance of ortho isomer may be due to its greater stability resulting from intramolecular hydrogen bonding (chelation) Further, due to intramolecular hydrogen bonding, ortho-isomer having lower boiling point can be separated from para-isomer by steam distillation H C O O N (xi) Coupling reaction: Ice cold solutions of phenols on treatment with arenediazonium salt solutions in weakly alkaline medium form brilliantly coloured compound called azo dyes + – – N2Cl + O Benzenediazonium chloride Phenoxide pH - 10 N N p-Hydroxyazobenzene (an orange dye) OH PHENOLS 175 (xii) Lederer-Manasse reaction: Phenols condense with aliphatic and aromatic aldehydes in presence of either an acid or a base as a catalyst The process can be exemplified by the reaction of formaldehyde with phenol in presence of acid or alkali forming o- and p-hydroxybenzyl alcohols (o-hydroxymethylphenol (I) and p-hydroxymethyl phenol (II)) which are important starting materials for the manufacture of a phenol formaldehyde resin called Bakelite OH OH CH2OH + CH2 Acid or base cold O + HO CH2OH II (Major) I ( Minor) But the reaction does not stop at this stage and the phenolic alcohols (I and II) condense with further amount of formaldehyde to form bishydroxymethyl phenols (III and IV) or with further amount of phenol to give all the possible dihydroxydiphenylmethanes (V, VI and VII) OH CH2OH 2CH2 O – + H or OH HOH2C CH2OH + Chapter I + II OH CH2OH III AND IV HO CH2 OH V + OH I + II + HO CH2 O – + H or OH HO CH2 VI + HO HO CH2 VII Such condensations are repeated and finally a polymeric resinous mass called Bakelite is obtained Bakelite is a thermosetting plastic and is very hard and rigid 176 ORGANIC CHEMISTRY [VOL-II] CH2 CH2 CH2 CH2 HO OH HO CH2 III + IV + V + VI + VII CH2 CH2 HCHO, – + H or OH HO OH CH2 CH2 CH2 OH CH2 HO CH2 CH2 Phenol - formaldehyde polymer (Bakelite) Mechanism: This also involves an electrophilic attack of formaldehyde or its conjugate acid on phenoxide (alkaline medium) or phenol (acidic medium), respectively Alkaline medium (dilute alkali) O H O – OH – O O CH2 H O CH2O O – CH2O – OH – H2O – CH2OH Acidic medium (dilute acid) + CH2 O + H CH2 + + OH CH2 OH + OH OH H + + CH2 OH OH CH2 + OH –H CH2 OH – PHENOLS 177 The mechanism of the polymerization in acidic and alkaline media may be depicted as under: Alkaline medium – O CH2 – OH O + H2 C O O + – CH2 O CH2 O CH2 O – H – OH O H2 C – etc O – CH2 O HO CH2 OH + H HO Chapter Acidic medium + OH2 CH2 –H2O + + HO HO H2 C CH2 + HO CH2 OH O CH2 + HO – H –H + +H + + H2 C etc OH HO CH2 OH (xiii) Hydroxylation: Phenols, particularly polyhydric phenols, upon fusion with alkali form the product(s) having more hydroxyl groups attached to the aromatic ring For instance, when quinol is heated rapidly with a large excess of sodium hydroxide, hydroxyquinol is formed together with other products The reaction probably involves nucleophilic displacement of hydride by hydroxide ion 178 ORGANIC CHEMISTRY [VOL-II] OH OH – OH H – + OH OH OH OH – –H OH OH Most convincing evidence for the above mechanism comes from the fact that hydrogen is evolved during the course of this reaction (xiv) Oxidation: As the phenols are able to readily donate electrons(s) to various oxidizing agents, they are susceptible to oxidation This is the reason why phenols turn pink or brown on exposure to air and light The colour change may be attributed to the formation of quinones and phenoquinones Different products are obtained using different reagents Some examples are discussed below: (a) Oxidation with alkaline KMnO4 or stronger oxidising agents: Oxidation of phenols with stronger oxidising agents such as alkaline KMnO4 leads to the cleavage of the aromatic ring However, if the —OH group is protected by alkylation or acylation, the alkyl side chain can be oxidised to give the corresponding hydroxy acids – CH3 CH3 COO CH3COCl COOH + H 3O KMnO4 –HCl OH O COCH3 O COCH3 OH (b) Oxidation with weaker oxidising agents such as ferric chloride: Oxidation of phenols with ferric chloride leads to the formation of a phenoxyl radical which is resonance stabilized and undergoes radical coupling reaction at ortho-ortho, ortho-para, para-para positions, as shown below: O H + Fe O O +3 O H O + Fe+2 H H Radical coupling O O O H H + ortho-ortho coupling H ortho-para coupling O + O O H para-para coupling PHENOLS 179 (c) Oxidation with alkaline potassium persulphate: Monohydric phenols, upon treatment with potassium persulphate in alkaline solution, undergo oxidation yielding dihydric phenols The —OH group enters preferentially at p-position if it is free otherwise it goes to o-position This reaction is known as Elbs persulphate oxidation K2S2O8 – OH OH OH OH Hydroquinone Phenol OH K2S2O8 – OH OH CH3 CH3 p-Cresol OH 4-Methylcatechol Mechanism H – – O O SO3 – SO3 O SO3 O SO3 + SO4 + – HO 2– O Chapter O –H + H3O OH – – O (xv) Liebermann’s nitroso reaction: Phenol, upon treatment with sodium nitrite and conc H2SO4, gives a deep green or blue colour which changes to red on dilution with water When the resulting solution is made alkaline with sodium hydroxide the green or blue colour is restored This reaction, known as Liebermann’s nitroso reaction is used as a test for the detection of phenol OH O H O N O p-Nitrosophenol N Sodium salt (Blue or green) OH H2SO4 N OH Quinone monoxime – + O H + –H + +H NaNO / HCl ONa NaOH O N OH Phenol - indophenol ( Red ) (xvi) Formation of phthaleins or fluoresceins: On heating with phthalic anhydride, phenols (in the ratio : 2) in presence of an acid catalyst such as anhydrous ZnCl2 or AlCl3 or conc H2SO4 afford phthalein or fluorescein dyes which give characteristic colour in alkaline medium Whereas monohydric phenols yield phthaleins, polyhydric phenols give fluoresceins 180 ORGANIC CHEMISTRY [VOL-II] OH HO O H C O OH + C C H2SO4 –H2O H O C OH O O Phenol (Monohydric) Phthalic anhydride Phenolphthalein (pink in alkaline medium) OH HO O O OH C C O H2SO4 –H2O + C O O C OH Resorcinol (Dihydric) O Fluorescein (yellow-green fluorescence in alkaline medium) Phthalic anhydride Phenolphthalein is used as an indicator in acid-base titrations It is colourless in acidic medium and turns pink in alkaline medium (xvii) Reduction: Phenols on heating with zinc dust, form aromatic hydrocarbons OH + Zn Δ + ZnO However, catalytic reduction gives cycloalkanols involving saturation of the ring OH OH + 3Zn 4.8 Ni 433 K DISTINCTIONS BETWEEN ALCOHOLS AND PHENOLS (i) Litmus test: Phenols turn blue litmus red but alcohols not (ii) Coupling reaction: Phenols react with diazonium salts at pH 9-10 to form yellow or orange azodyes but alcohols not PHENOLS 181 (iii) FeCl3 test: Phenols react with neutral FeCl3 to give blue, violet or green colour but alcohols not (iv) Br 2/H 2O test: Phenols give a white precipitate of polybromophenols (e.g., 2, 4, 6-tribromophenol in case of phenol) but alcohols not A BRIEF REVIEW (iv) phenol itself is obtained from cumene by catalytic aerial oxidation Phenols are stronger acids than alcohols The phenoxide ion is resonance stabilized while alkoxide ion is not Effect of substituents on acid strength of phenols (i) Electron-donating groups decrease the acid strength of phenols Thus the order of acid strength is phenol > m-cresol > p-cresol > o-cresol (ii) Electron-withdrawing groups increase the acid strength of phenols Thus the order of acid strength is p-nitrophenol > o-nitrophenol > m-nitrophenol > phenol Effect of position of substituents The increase or decrease in acid strength of phenols is more pronounced at o- and p-positions than at m-position because a group present at m-position can not enter into resonance with the phenoxide ion m-Methoxyphenol and m-aminophenol are, however, more acidic than phenol due to –I-effect of the —OCH3 or the —NH2 group, i.e, m-methoxyphenol > phenol > o-methoxyphenol > p-methoxyphenol Sodium or potassium phenoxide reacts with alkyl halides to form phenolic ethers The reaction is called Williamson’s synthesis Allyl phenyl ethers when heated to 475 K, undergo Claisen rearrangement to form o-allylphenols If both the ortho positions are occupied, the allyl group migrates to p-positions This reaction, occuring by a concerted mechanism through a six-membered cyclic transition state, is also called as Sigmatropic rearrangement Phenols react with acid chlorides or anhydrides in presence of pyridine to form esters With acetyl chloride or acetic anhydride, phenol gives phenyl acetate It is called acylation Benzoylation of phenol with benzoyl chloride in presence of NaOH gives phenyl benzoate (Schotten-Baumann reaction) The acetyl group migrates to o- and p-positions to form a mixture of o-hydroxyacetophenone and p-hydroxyacetophenone when phenyl acetate is heated in presence of anhyd AlCl3 Under similar conditions, phenly benzoate gives a mixture of o- and p-hydroxybenzophenone This reaction is called Fries rearrangement and usually occurs in two steps Phenols but not alcohols on distillation with zinc dust give the corresponding aromatic hydrocarbons Due to the presence of strongly activating OH group, phenols readily undergo electrophilic substitution reactions (i) With conc HNO3 in presence of conc H2SO4, phenol gives picric acid But the yield is poor (ii) With dil HNO3 at 293 K, phenol gives a mixture of o-nitrophenol (major) and p-nitrophenol (minor) Chapter Phenols are obtained by: (i) treating halobenzenes with NaOH under suitable conditions (Dow process) (ii) fusion of sodium salts of aromatic sulphonic acids with NaOH at 573–623 K followed by acidification with dil H2SO4 (iii) hydrolysis of benzene diazonium salts with boiling dil H2SO4 182 ORGANIC CHEMISTRY [VOL-II] (iii) With conc H2SO4 at 288–293K, phenol gives o-phenolsulphonic acid as the major product, but at 373 K it gives p-phenolsulphonic acid as the major product (iv) With Br2 in CS2 at 273 K, a mixture of p-bromophenol (major) and o-bromophenol (minor) is obtained (v) With Br2 water phenol gives 2,4,6-tribromophenol (vi) With alkyl halides in presence of anhyd AlCl3, phenol give a mixture of o-alkylphenol (minor) and p-alkylphenol (major) (vii) Sodium phenoxide when heated with CO2 at 400K under a pressure of 4–7 atmospheres followed by acidification gives salicylic acid (Kolbe’s reaction) Since by this reaction, a carboxyl group is directly introduced into the aromatic ring, this reaction is also called carboxylation (viii) Phenol mainly gives p-hydroxybenzaldehyde when treated with a mixture of HCN + HCl in presence of anhyd AlCl3 This reaction is called Gattermann formylation because a formyl group is directly introduced into the aromatic ring (ix) Houben-Hoesch reaction is an extension of Gattermann formylation and involves acylation of highly reactive polyhydric phenols having two or three hydroxyl groups at m-position to each other The reaction is usually carried out by passing HCl gas through a cold ethereal solution of a polyhydric phenol and acetonitrile in presence of anhyd AlCl3 or ZnCl2 when the ketimine hydrochloride gets precipitated This upon subseqent hydrolysis with boiling water gives the corresponding phenolic ketone Under these conditions, phloroglucinol gives phloroacetophenone (x) Phenol reacts with CHCl3 in presence of NaOH at 340 K to form salicylaldehyde as the major product alongwith a small amount of p-hydroxyaldehyde The reaction involves electrophilic attack of dichlorocarbene on phenoxide ion and is called Reimer-Tiemann reaction If CCl4 is used in place of CHCl3, salicylic acid is the main product (xi) When phenol is treated with formaldehyde in presence of an acid or a base, it initially gives a mixture of o-and p-hydroxymethylphenols This reaction is called Lederer-Manasse reaction The phenolic alcohols thus produced subsequently undergo polymerization to form a highly crosslinked threedimensional polymer called Bakelite (xii) Phenol condenses with phthalic anhydride in presence of conc H2SO4 to form phenolphthalein which is used as an indicator in acid-alkali titrations (xiii) Phenol reacts with benzenediazonium salt in presence of weakly alkaline solution (pH 9–10) at 273–278 K to form brilliant coloured compounds called azo dyes Distinction of phenols from alcohols Phenols (i) turn blue litmus red (ii) give blue or violet colour with neutral FeCl3 (iii) produce white ppt with bromine water and (iv) form yellow or orange coloured azo dyes with diazonium salts Alcohols not respond to these tests SOLVED PROBLEMS Q.1 Explain why alochols react with organic acids to form esters but phenols not Ans Nucleophilic attack of alcohols occurs on the protonated carbonyl group of carboxylic acids during formation of esters + OH O OH + R OH + R C OH R O C H OH R + –H2O, –H R O C R Protonated acid But phenols, are less nucleophilic than alcohols because of resonance which deplete the electron density on oxygen Due to this they fail to attack the protonated carbonyl group of acids to form esters PHENOLS 183 H H + O + O H + O H O OH – – – Resonating forms of phenol Q.2 Explain why phenols not undergo substitution of the —OH group in contrast to alcohols? Ans The C—O bond in alcohols has single bond character and hence can be cleaved by a nucleophile But the C—O bond in phenols has some double bond character due to resonance and hence cannot be easily cleaved by a nucleophile Q.3 Explain why the compound I is more acidic than? OH OH CH3 H3C CH3 NO2 NO2 I II Ans In phenol II, the nitro group is flanked by two groups which push the nitro group out of the plane of the benzene ring As a result of this steric hindrance, the electron-withdrawing resonance effect of the nitro group will be reduced However, in phenol I, no such steric inhibition of resonance occurs In other words, the phenoxide ion obtained from I is better stabilized by the nitro group than the phenoxide ion derived from phenol II Thus, phenol I is more acidic than II Q.4 Alcohols react with halogen acids or phosphorus halides to form haloalkanes but phenols not form halobenzenes Explain Ans The C—O bond in phenols has some double bond character due to resonance and hence cannot be – easily cleaved by X ions in presence of halogen acids or phosphorus halides to form halobenzenes – In contrast, the C—O bond in alcohols is a single bond and hence can be easily cleaved by X ions in presence of halogen acids or phosphorus halids to form haloalkanes Q.5 Explain why dipole moments of phenol (1.7D) and methanol (1.6D) are in opposite directions Ans Delocalization of electron-density from O to the benzene ring makes the O of phenols to be the positive end of the molecular dipole In alcohols, the strongly electron-withdrawing oxygen is the negative end of the dipole Thus, the two dipoles act in opposite directions Q.6 Account for the fact that phenols are much more stable than enols Ans Both phenols and enols can be considered as tautomers of the respective keto forms The large resonance energy of C==O usualy makes the keto-tautomer much more stable than the enol form However the large resonance energy of the aromatic ring makes phenol more stable than the keto form O OH O H C H o-Keto form H H C Enol form OH H C C O Keto form p-Keto form Q.7 How you account for the fact that unlike phenol, 2,4-dinitrophenol and 2,4,6-trinitrophenol are soluble in aqueous sodium carbonate solution? Chapter H3C 184 ORGANIC CHEMISTRY [VOL-II] Ans Due to strong electron-withdrawing nature of NO2 groups both 2,4-dinitrophenol and 2,4,6-trinitrophenol are more acidic than carbonic acid and hence decompose Na2CO3 solution to form the corresponding sodium salts with the evolution of CO2 Q.8 Consider the following reaction sequence for the synthesis of benzaldehyde C6H6 + CO + HCl AlCl3, 100 atm C6H5CHO + HCl If we use DCl in place of HCl, shall we get C6H5CHO or C6H5CDO? Give reason for your answer – Ans C + O + HCl + AlCl3 + HC – O + AlCl4 ⊕ If instead of HCl, DCl is used, then D — C == O will be formed which will attack the benzene ring to form deuterated benzaldehyde C6H6 + CO + DCl AlCl3, 100 atm C6H5CDO + HCl Q.9 Out of o- and p-nitrophenols which one has higher boiling point and why? Ans o-Nitrophenol exists as discrete molecules due to intramolecular H-bonding while p-nitrophenol exists as associated molecules due to intermolecular H-bonding Therefore, p-nitrophenol has higher boiling point than o-nitrophenol Q.10 How will you distinguish between the following pairs?: (i) Phenol and benzaldehyde (ii) Phenol and benzoic acid (iii) Phenol and ethyl alcohol Ans (i) Phenol on heating with phthalic anhydride and a few drops of conc H2SO4 gives phenolphthalein which gives pink colour with NaOH while benzaldehyde fails to give this test (ii) Benzoic acid gives brisk effervescence with aqueous solution of NaHCO3 while phenol does not give this test, C6H5COOH + NaHCO3 → C6H5COONa + CΟ2↑ + Η2Ο (iii) Phenol gives purple colour with neutral FeCl3 solution whereas ethyl alcohol does not respond to this test Q.11 m-tert-Butylphenol reacts with chlorine forming a trichloroderivative but with iodine it forms only monoiodo derivative Explain Ans Steric hindrance by bulky tert-butyl group does not allow the large sized iodine atom to attack at positions ortho to it As a result, I attacks only at o-position with respect to OH group to give monoiodo derivative In contrast Cl atom is much smaller and hence attacks at all the o- and p-positions with respect to OH group to form trichloro derivative Q.12 The boiling point of toluene is 384 K while that of phenol is 455 K Explain Ans More energy is required to break intermolecular H-bonds existing in phenol compared to weak van der Waals forces of attraction existing in toluene Q.13 2, 6-Di-tert-butylphenol is a much weaker acid than phenol Why? Ans Bulky o-tert-butyl groups prevent solvation of the corresponding phenoxide anion thus making it less stable than phenoxide ion Q.14 What are the principal ions in solution when the following are mixed? (i) Sodium ethoxide and phenol (ii) Sodium phenoxide and ethanol Ans (i) C2H5ONa + C6H5OH ⎯→ C2H5OH + C6H5ONa Phenol being a stronger acid than alcohol displaces ethanol from sodium ethoxide Thus ethanol and sodium phenoxide are formed (ii) Nothing will happen Q.15 Arrange the following in increasing order of solubility in water: C2H5OH, C6H5CH2OH, C6H5OH PHENOLS 185 Ans Solubility decreases as the length of the carbon chain or the size of the hydrocarbon part increases Thus, solubility increases in the order: C6H5CH2OH < C6H5OH < C2H5OH Q.16 Treatment of phenols with alkyl halides in presence of KOH results in the formation of only O-alkylated produts by SN process But 2, 6-di-tert-butylphenol give a mixture of C-alkylated and O-alkylated products Further, the amount of C-alkylated product increases with the increase in the size of alkyl group of alkyl halides Explain Ans In presence of KOH, SN attack of phenoxide ion occurs on alkyl halide to form alkyl aryl ethers – – Ar O + R X ArO R + X However, SN attack of 2,6-di-tert-butylphenoxide ion on alkyl halide is sterically hindered due to the presence of bulky tert-butyl groups at o-positions The negative charge is also available at p-position due to resonance Since this position is sterically unhindered, preferential nucleophilic attack occurs at this position to give C-alkylated product as the major product O Sterically hindered R – O O – O X R – –X O X – –X + –H – O-Alkylated product (not formed) H R R C-Alkylated product Further, as expected, as the size of the alkyl group in alkyl halide increases, steric hindrance for Oalkylation increases Therefore, the amount of O-alkylated derivative decreases while that of C-alkylated product increases Q.17 Houben-Hoesch reaction occurs with polyhydric phenols having two or three hydroxyl groups at m-position with respect to each other but not with phenols having hydroxyl group at o- and p-positions Why? Ans Monyhydric phenols react with alkyl cyanide and HCl in presence of anhydrous AlCl3 (Houben-Hoesch reaction) to form mainly imido esters Ar OH + HCl + R C N R Anhydrous AlCl3 + C Ar O – NH2Cl Imido ester However, when two or three OH groups are present at m-position with respect to each other, the reactivity of the nuclear positions, o- and p- to the hydroxyl group increases to such an extent that nuclear acylation occurs preferentially The reactivity of the nuclear position does not increase significantly when the two OH groups are at o- and p-positions and hence the reaction does not occur with phenols having two hydroxyl groups at o- and p-positions with respect to each other UNSOLVED PROBLEMS What are phenols? Describe three methods by which benzene can be converted into phenol Why are phenols more acidic than alcohols? Discuss the effect of substituents on the acid strength of phenols Chapter R 186 ORGANIC CHEMISTRY [VOL-II] Compound (A), C7H8O is insoluble in aqueous sodium bicarbonate but dissolves in aqueous sodium hydroxide and gives characteristic colour with aq ferric chloride When treated with bromine (A) forms a compound (B), C7H5—OBr2 (i) Give the structural formulae for (A) and (B) (ii) What would be the structure of compound (A) if it neither dissolves in aqueous sodium hydroxide nor gives a characteristic colour with ferric chloride solution? Write IUPAC names of the following compounds: OH H3C OH OH CHO ( i) OH CHO ( ii) (iii) H3C NO2 Br (iv) COOCH3 NO2 CH3 Cl What is cumene? How can it be prepared and how can it be converted into phenol? Describe Dow’s process for the manufacture of phenol Comment upon its mechanism Explain the following: (a) Phenol has higher boiling point than toluene (b) Phenol is more soluble in water than toluene (c) o-Nitrophenol has lower melting point and decreased water solubility as compared to its m- and p-isomers (d) p-Nitrophenol is a stronger acid than phenol Discuss the mechanism of the following: (a) Fries rearrangement (b) Claisen rearrangement (c) Gatterman synthesis (d) Hauben-Hoesch reaction (e) Reimer-Tiemann reaction (f ) Lederer-Manasse reaction How does phenol react with the following reagents? (a) Zinc dust/Δ (b) Br2/H2O (c) HNO3 (d) Conc H2SO4 (e) HNO2 (f ) H2/Ni 10 Identify compounds A, B, C and D in the following sequence of reactions: o-Nitrophenol (CH3)2SO4 NaOH A Zn, HCl B NaNO2, HCl 273K C C2H5OH D 11 How would you distinguish between o- and p-hydroxybenzaldehydes on the basis of infrared spectral studies? 12 Compare the acid strengths of (a) p-Chlorophenol and p-nitrophenol (b) 2,4-Dinitrophenol and 2,4,6-trinitrophenol (c) o-Aminophenol and p-aminophenol 13 Arrange, giving appropriate reasoning, the following sets in order of increasing acid strength: (a) Benzenesulphonic acid, benzyl alcohol, phenol, benzoic acid (b) Phenol, o-nitrophenol, p-nitrophenol 2,4-dinitrophenol 2,4,6-trinitrophenol PHENOLS 187 (c) Phenol, m-anisole, p-chlorophenol, quinol, p-aminophenol, p-nitrophenol (d) m-Nitrophenol, m-bromophenol, m-cresol and phenol 14 Why does phenol turn pink on exposure to air and sunlight? Hint Phenol turns pink on exposure to air and light due to slow oxidation to produce quinone OH + O2 O O + H2O Quinone then combines with phenol through hydrogen bonding to form brilliant red adduct known as phenoquinone OH + O O + HO OH O O HO 15 Explain, why phenols couple more readily in slightly basic than in acidic solution 16 Introduction of nitro group in aromatic ring increase the acidic character of phenol while introduction of methyl group decreases its acid strength Explain 17 Complete the following reaction and name the products and the reaction involved ONa + CO2 398K, – atom + H 18 How will you synthesize butyl phenoxyethanoate (A) using phenol, acetic acid and any other chemical you wish? OCH2COOCH2CH2CH2CH3 (A) 19 (i) With the help of resonance contributing structures, show how the presence of a nitro group in the ortho and para positions stabilizes the phenolate anion while that in the meta position it does not? (ii) Why does p-nitrophenol not form intramolecular hydrogen bond? 20 Predict the products in the following transformations: (i) p-Cresol NaOH CO2, 373K, Pressure H (iii) p-Chlorophenol HNO3, H2O (ii) p-Cresol + 2Br2 (iv) p-Bromophenol + (CH3)2SO4 – OH H2O Chapter Phenoquinone (Brilliant red compound) 188 ORGANIC CHEMISTRY [VOL-II] – OH (v) C6H5OH + ClCH2COOC2H 21 Predict the products(s) and sketch a plausible mechanism for each of the following reactions: OH CHO K2S2O8 (i) (ii) NaOH + H2O2 OH Cl OH (iii) OH + (CH3CO)2O + H (iv) + C6H5COCl – OH OH (v) – CHCl3, OH 22 Sketch the mechanism for the following transformation: CH(CH3)2 OH O2, 368–408K Dilute H2SO4 H3 C C + O H3C ❑❑❑ [...]... in the order: p-Nitrophenol > o-Nitrophenol > m-Nitrophenol > Phenol Further, greater the number of electron withdrawing groups at o- and p-positions, more stable is the phenoxide ion and hence more acidic is the phenol Thus, acid strength of nitrophenols with respect to phenol decreases in the order: 2,4,6-Trinitrophenol > 2,4-Dinitrophenol > 4-Nitrophenol or 2-Nitrophenol > Phenol (b) Inductive and... o-nitrophenol and p-nitrophenol are stronger acids than m-nitrophenol Out of o-nitrophenol and p-nitrophenol, o-nitrophenol is little less acidic than p-nitrophenol This may be due to the fact that acidic hydrogen of OH group is involved in intramolecular H-bonding or chelation which makes loss of the proton a little more difficult O + O N – H O Thus, the acid strength of nitrophenols relative to phenol. .. preparing o- and p-nitrophenols, phenol is treated with dilute nitric acid The reaction most probably, involves initial nitrosation of phenol with dinitrogen trioxide produced from nitric acid in situ The nitrosophenol is then oxidized to nitrophenol OH OH N2O3 OH NO HNO3 NO2 [O] o- and p-Nitrophenol o- and p-Nitrosophenol m-Nitrophenol cannot be prepared by direct nitration of phenol It may be prepared... strength of phenol with m-methoxyphenol and m-aminophenol A group present at m-position cannot enter into resonance with the hydroxy group of phenols, but can exert inductive effect from this position Due to –I-effect of both methoxy and amino groups, m-methoxyphenols and m-aminophenols are more acidic than phenol Futher, due to more –I-effect of methoxy group than of amino group, m-methoxyphenol is... Comparison of the acidic strength of halophenols Halogens have +R and –I-effects, but the –I-effect predominates over the +R-effect Therefore, all halophenols (except p-fluorophenol) are more acidic than phenol itself Further, since –I-effect decreases with distances, the acidic strength of halophenols decreases in the order: o-Halophenol > m-Halophenol > p-Halophenol Chapter 4 Resonance stabilization... the acid strength of phenols Thus the order of acid strength is p-nitrophenol > o-nitrophenol > m-nitrophenol > phenol Effect of position of substituents The increase or decrease in acid strength of phenols is more pronounced at o- and p-positions than at m-position because a group present at m-position can not enter into resonance with the phenoxide ion m-Methoxyphenol and m-aminophenol are, however,... halogen decreases F H O Therefore, the acid strength of all the o-halophenols decreases in the order: o-Chorophenol > o-Bromophenol > o-Iodophenol > o-Fluorophenol (ii) Comparison of the acidic strength of cresols The alkyl groups are electron donating due to hyperconjugation effect Therefore, all cresols (methylphenols) are less acidic than phenol itself Futher, hyperconjugation effect cannot operate at... ALCOHOLS AND PHENOLS (i) Litmus test: Phenols turn blue litmus red but alcohols do not (ii) Coupling reaction: Phenols react with diazonium salts at pH 9-10 to form yellow or orange azodyes but alcohols do not PHENOLS 181 (iii) FeCl3 test: Phenols react with neutral FeCl3 to give blue, violet or green colour but alcohols do not (iv) Br 2/H 2O test: Phenols give a white precipitate of polybromophenols (e.g.,... 6-tribromophenol in case of phenol) but alcohols do not A BRIEF REVIEW (iv) phenol itself is obtained from cumene by catalytic aerial oxidation Phenols are stronger acids than alcohols The phenoxide ion is resonance stabilized while alkoxide ion is not Effect of substituents on acid strength of phenols (i) Electron-donating groups decrease the acid strength of phenols Thus the order of acid strength is phenol. .. —OR etc., when present in m-position increase the acid strength of phenols due to –I effect The order of acid strength for some typical phenols is as under: OH OH > OH OH > NO2 > > CH3 Cl p-Nitrophenol OH p-Chlorophenol Phenol OCH3 p-Cresol p-Methoxyphenol Thus, in nutshell, electron-withdrawing substituents increase the acid strength of phenols while electron-donating substituents decrease their acid