Chapter-5 , Ethers and Phenols

A) Alcohols: Defination: The hydroxyl derivatives of alkanes are called as alcohols, in which one or more hydrogen atoms of alkane are replaced by hydroxyl groups. It is represented as R-OH. Classification of alcohols: Depending upon the number of hydroxyl groups present in the molecule, alcohols are classified as below.

Monohydric alcohols: They contain only one hydroxyl group and having general formula CnH2n+1-OH or R- OH where R is an alkyl group. Monohydric alcohols further classified on the basis of carbon atom to which hydroxyl i.e. –OH group is attached. 1) Primary alcohols (10): When –OH gr. is attached to primary carbon atom then it is called as primary alcohols.e.g.-

Hence primary alcohols contain –CH2OH group. 2) Secondary alcohols (20): When –OH gr. is attached to secondary carbon atom then it is called as secondary alcohols. e.g.-

3) Tertiary alcohols (30): When –OH gr. is attached to tertiary carbon atom then it is called as tertiary alcohols. E.g.-

IUPAC Nomenclature: 1) First select longest carbon chain of parent alkane containing –OH gr. 2) Numbering given in such way that hydroxyl carbon should get lowest number. 3) Last letter ‘e’ of corresponding alkane is changed to ‘old’. Consider following examples-

Physical Properties: 1) Alcohols are neutral in nature.

2) Lower members are liquids (C1-C12) & higher members are solid. 3) Solubility: Lower alcohols soluble in water due to formation of hydrogen bonding of alcohols with water. But as we increase molecular weight (higher member) of alcohols its solubility decreases because of increasing hydrocarbon character (non-polar nature). 4) M.P.and B.P.: 1) As carbon chain increases boiling point increases. E.g. Methyl B.P. 64.5 0C while n-pentyl alcohol boils at 138 0C . 2) As branching increases boiling point of alcohol decreases because intermolecular force of attractions between the molecules decreases. E.g. n- butyl alcohol B.P. 118 0C while t-butyl alcohol B.P. is 83 0C.

CH3

H3C OH H3C OH CH 0C 3 n-butyl alcohol B.P. 118 0 t-butyl alcohol B.P. 83 C 3) Boiling point of alcohols higher than hydrocarbons of comparable same molecular weight. E.g. n-pentane (Mol. Wt. 72) B.P. 36 0C, while n-butyl alcohol (Mol. Wt. 74) has B.P. 118 0C .

H3C OH 0C n-pentane B.P. 36 n-butyl alcohol B.P. 118 This is because of alcohol molecules associated together strongly by intermolecular hydrogen bonding. Hence alcohol boils at high temp. But incase of alkanes (Hydrocarbons) intermolecular force of attraction weak therefore hydrocarbons has lower B.P.

Preparation of Alcohols: We can prepare alcohols by using following methods.

1) Using Grignard reagent: ( R-Mg-X) By using Grignard reagent we can prepare primary, secondary & tertiary alcohols. During this preparation or treated with Grignard reagent (RMgX) in presence of ether as a solvent first it forms Grignard complex, which on acid hydrolysis we get alcohol.

a) : e.g. preparation of ethyl alcohol.

Only formaldehyde reacts with Grignard reagent (e.g. CH3-Mg-Br) followed by hydrolysis we get primary alcohol ethyl alcohol.

b b) Secondary alcohol: e.g. preparation of propan-2-ol or isopropanol / . Acetaldehyde on reacted with methyl magnesium bromide as a Grignard reagent we get isopropanol.

H3C CH3 CH3 CH3-Mg-Br H2O O H3C C OMgBr H3C C OH + Mg(OH)Br Ether H+ H H H Acetaldehyde Complex Propan-2-ol / Isopropanol c) Tertiary alcohol: e.g. Preparation of t-butyl alcohol / 2-methyl propan-2-ol. All ketones reacted with Grignard reagent we get tertiary alcohol. When treated with methyl magnesium bromide we get t- butyl alcohol.

H3C CH3 CH3 CH3-Mg-Br H2O O H3C C OMgBr H3C C OH + Mg(OH)Br Ether H+ H C 3 CH CH Acetone 3 3 Complex 3- mehtyl Propan-2-ol / t- d) Primary alcohol from ethylene oxide: Grignard reagent Ph-Mg-Br reacts with ethylene oxide () it forms primary alcohol 2-phenyl or β-phenyl ethyl alcohol.

e) From ester: Ethyl format treated with excess Grignard reagent we get secondary alcohol. e.g. Preparation of isopropanol.

2) Catalytic Reduction of aldehydes/ketones:

Aldehyde or on reduction using H2 in presence of catalyst like Pt, Pd or Raney Ni we get corresponding alcohol. gives primary alcohol while ketone gives secondary alcohol.

3) Reduction with sodium amalgam & water/acid: Na-Hg & water can form nascent hydrogen & which reduces aldehydes to primary alcohol and ketone to secondary alcohol. e.g.

4) Reduction with Lithium Aluminum Hydride (LiAlH4): LiAlH4 is a very specific & stronger reducing agent. It reduces saturated/ unsaturated aldehydes or ketones into saturated/ unsaturated alcohols. LiAlH4 does not reduce carbon carbon double bond.

In this reaction aldehydes/ketones treated with LiAlH4 in ether as a solvent, first it forms complex & which on treated with dil.HCl to form alcohol. e.g.

5) Reduction of carboxylic acids:

LiAlH4 + Carboxylic acid we get complex & which on acid hydrolysis get alcohol.

Reactions of alcohols: Two types of reactions take place by alcohol.

A) Reactions involving replacement of –OH group: 1. Formation of Alkyl halide (R-X):

Alcohol is converted into alkyl halides using reagents like H-X, PX3 & SOCl2 as below. a) Using H-X: Alcohol heated with haloacids like HCl, HBr or HI in presence of anhydrous

ZnCl2 we get corresponding alkyl halides. Lucas reagent: Lucas reagent is nothing but a mixture of HCl & anhydrous ZnCl2. Reactivity of H-X decreases in order of HI > HBr > HCl and among the alcohols reactivity order is tertiary > secondary > primary alcohol.

b) Using phosphorous halides: (PX3) Alcohol reacts with phosphorous trihalides like PCl3, PBr3 PI3 to get alkyl halides.

c) Using Thionyl Chloride ( SOCl2): When alcohol treated with thionyl chloride (SOC2) in presence of pyridine as base we get alkyl halides. Pyridine CH -CH -Cl + SOCl + HCl CH2- CH2- OH + SOCl2 3 2 2 Ethyl chloride Ethyl alcohol d) Iodoform test: Only those alcohols which containing structure as below gives positive iodoform test

when it is treated with I2 & NaOH (sodium hypoiodite NaOI). H

R OH

CH3 e.g. Ethyl alcohol, isopropyl alcohol. 2-pentanol, 1-phenyl ethanol gives positive iodoform test. While methyl alcohol, t-butyl alcohol, 3-pentanol, 2-phenyl ethanol give negative iodoform test. B) Reactions involving replacement of ‘H’atom of –OH group: 1. Reactions with active metals (formation of alkoxides): Alcohols react with active metals like Na, K, Mg, Al etc. it forms alkoxide with liberation

of H2 gas. The order of reactivity decreases from CH3OH > primary > secondary > tertiary alcohol. e.g.

These alkoxides are used to prepare symmetrical as well as unsymmetrical ethers by Williamson’s synthesis. Williamson’s synthesis: In Williamson’s synthesis alkyl halides are reacted with alkoxide we get ether. Williamson’s synthesis used to prepare symmetrical as well as unsymmetrical ethers.

Note: Tertiary alkyl alcohol can not use for preparation of ether because they easily undergo & give instead of ether.

H CH3 CH3 Elimination + R-OH + HBr R-O H2C OH H2C CH alcohol CH3 3 alkoxide Alkene t-butyl bromide 2. Esterification:

Alcohols react with organic acids in presence of dehydrating agents like conc. H2SO4 or HCl to form ester. This process called as esterification. Reactivity order of alcohols for

esterification is CH3OH > primary > secondary > tertiary alcohol.

3. Oxidation of alcohols: Alcohols can oxidize by various following oxidizing agents. The nascent oxygen brings about oxidation. a) Oxidation by PCC (Pyridinium chlorochromate): PCC is special mild oxidizing agent for conversion of primary alcohol to aldehyde.

Preparation of PCC: PCC prepared from chromium trioxide (CrO3) + HCl + Pyridine. e.g. Oidation of to benzaldehyde.

b) Oxidation by alkaline KMnO4: Primary alcohol is oxidized to carboxylic acids in presence of hot KMnO4. When oxidation reaction is complete we get potassium salt of acid & brown ppt. of MnO2 is formed and purple colour of KMnO4 disappears.

c) Oxidation by acidic K2Cr2O7 : Using potassium dichromate we can carry out oxidation of primary & secondary alcohols. 1. Primary alcohol oxidation:

When primary alcohol treated with K2Cr2O7 / di. H2SO4 first it form aldehyde, further aldehyde again get oxidized by same oxidizing reagent to form carboxylic acid. e.g. Oxidation of ethyl alcohol into acetic acid.

2. Secondary alcohol oxidation: Secondary alcohol on oxidation to form ketone.

3. Tertiary alcohol oxidation: For oxidation of tertiary alcohol we require stronger oxidizing agent like chromium

trioxide (CrO3). Tertiary alcohols first oxidized into ketone with less no. of carbon atoms, further ketone again get oxidized into carboxylic acids. e.g. Oxidation of t-butyl alcohol into acetic acid.

4. Oxidation with conc. HNO3 : Oxidation of benzyl alcohol into benzoic acid is carried out by using conc. HNO3. O

OH OH Conc. HNO3 + NO2

Benzoic acid Benzyl alcohol 5. : Secondary alcohol treated with excess of acetone in presence of aluminum tertiary butoxide catalyst we get ketone.

6. Oxidation of : Pinacol-Pinacolone rearrangement: In this rearrangement migration of an atom or group of atom from one site to another with in same species.

e.g. When pinacol ( 2,3-dimethyl-butane 2,3-) is treated with dil. H2SO4, we get pinnacolone (ketone).

C) Ethers: Ethers are organic compounds containing -C-O-C- linkage. The general formula of ethers CnH2nO. Ether represented by formula R-O-R or Ar-O-Ar or R-O-Ar. Classification of ethers: Two class of ethers. 1. Symmetrical / Simple ether: When both the alkyl groups or both the aryl groups are same it is called symmetrical ether.

e.g. C2H5-O-C2H5 (Diethyl ether), dimethyl ether etc. 2. Unsymmetrical / mixed ether: When both the alkyl groups or both the aryl groups are different it is called unsymmetrical ether.

e.g. CH3-O-C2H5 (Ethyl methyl ether). Nomenclature of ethers: 1. Common names:

2. I.U.P.A.C. System: Larger group is chosen as the parent alkane.

Physical properties of ether: 1. Boiling point: B.P. of ether is much lower than those of alcohols of comparable same molecular weight. e.g. B.P. of n-hexyl alcohol is higher than methyl-n-pentyl ether why? O H C CH H3C OH 3 3

n-hexyl alcohol B.P. 157 0C Methyl-n-pentyl ether B.P.1000C Mol. wt. 102 Mol. wt. 102 Because in n-hexyl alcohol intermolecular hydrogen bonding hence molecular association takes place strongly. While in ether no hydrogen bonding possible. Hence alcohol having higher B.P. than ether. H

O O R H R

Preparation of ether: Following different methods are used to prepare ether. 1. By Dehydration of alcohol ( Continuous etherification reaction): 0 When alcohols on heating with conc. H2SO4 at 140 C to form alkyl hydrogen sulphate, further which reacts with excess alcohol to form symmetrical ether. During this reaction water is lost for every two pair of alcohols. Hence it is called continuous etherification.

2. Williamson synthesis: This is most important method to prepare symmetrical as well as unsymmetrical ether. When alkyl halides is treated with sodium alkoxide (R-ONa) or sodium phenoxide we get corresponding ether.

3. Alkoxy mercuration-demercuration: react with mercuric trifluoroacetate in presence of alcohol to form Alkoxy

mercurial compounds, which on reduction with NaBH4 we get ether.

. 4. Diazomethane method: This is the special method for preparation of methyl ether only. When alcohol or phenol

is heated with diazomethane (CH2N2) in presence of HBF4 (fluoroboric acid) we get methyl ether.

Reactions of ethers: (Cleavage of ether by acid) Ether is unreactive towards bases, oxidizing agents & reducing agents. But under vigorous conditions ether undergo cleavage reactions with conc. acids like HI, HBr at high temp. 1. Reactions of ether with conc. HI: A) Cold conditions: Symmetrical ether (simple ether) e.g. diethyl ether reacts with conc. HI in cold condition to gives ethyl alcohol & ethyl iodide. Cold 00C

C2H5-O-C2H5 + H-I C2H5OH + C2H5I Diethyl ether But unsymmetrical ether (mixed ether) e.g. ethyl methyl ether reacts with conc. HI in cold condition to give methyl iodide & ethyl alcohol. Here larger group forms alcohol. Cold 00C

C2H5-O-CH3 + H-I C2H5OH + CH3I Ethyl methyl ether B) Hot condition: In hot condition when ether treated with conc. HI to form alkyl iodide.

Alcohol formed in first step again it reacts with HI to form alkyl iodide.

CH3 CH3 CH3 48% H-Br 140 0C CH CH CH 2 H3C Br H3C O CH3 Isopropyl bromide Di-isopropyl ether Alkyl aryl ether e.g. anisole undergoes cleavage of alkyl oxygen bond & not aryl oxygen bond. Because C-O of aromatic ring is stronger than C-O bond of methyl group. Hence we get phenol & methyl iodide. OH

O CH3 H-I + CH3-I

Anisole or methyl phenyl ether 2. Reaction with dil. H2SO4 ( Hydrolysis): Symmetrical as well as unsymmetrical ether undergoes hydrolysis with dil. H2SO4 under pressure to give two moles of alcohol.

C) Phenols: Definition: When hydroxyl group (-OH) attached to an aromatic ring it is called phenol. OH OH OH

OH

OH CH3 Phenol Resorcinol B-napthol m-cresol Nomenclature of phenols: 1. Simple method: Substituent attached on aromatic ring with respect to –OH group is designated as a ortho (o), meta (m), or para (p) OH OH OH OH

Cl (o) (o)

(m) (m) Br (p) m-bromophenol p-chlorophenol Phenol o-chlorophenol CL Methyl phenols called cresols e.g. OH OH OH

CH3

CH3 o-cresol m-cresol p-cresol CH3 Benzene diols have special names e.g.

OH OH OH

OH

OH Catachol Resorcinol Hydroquinone 1,2-benzenediol 1,3-benzenediol OH 1,4-benzenediol ii. Numbering method: The carbon atom of the aromatic ring to which –OH group is attached is given number 1, then other substituent of ring. OH OH OH 1 1 1 Cl 2 2 2

3 3

CH3 4

3-methyl phenol NH 4-aminophenol 2-chlorophenol 2 Polysubstituted derivatives: If more than two substituent’s attached to aromatic ring then only numbering method used. E.g. OH OH OH

1 1 1 NO2 O2N 2 NO2 2 2 6 5 3 3 5 3 Cl Br 4 4 4 2,4,6-trinitrophenol 3-bromo-5-chlorophenol NO2 NO2 (picric acid) 2,4-dinitrophenol

Physical properties of phenol: 1) Acidic nature of phenol: e.g. Alcohols are neutral but phenol is acidic in nature why? Phenol is acidic in nature, because after loss of proton we get phenoxide ion as a conjugate base which is more stable due to –R effect (electron withdrawing resonance effect) of benzene ring. But alcohols are neutral in nature because conjugate base ethoxide ion less stable due to +I (electron donating inductive effect) of ethyl group.

Phenol reacts with base NaOH to form sodium phenoxide salt.

Ar-OH + NaOH Ar-O Na + H2O

sodium phenoxide salt phenol Salt on treatment with HCl gives phenol ppt.e.g.

Ar-O Na + HCl Ar-OH + NaCl phenol sodium phenoxide salt ii. Physical constants: Boiling points of phenol higher than hydrocarbon of comparable same molecular weight. This is because phenol contains hydrogen bonding. Such a hydrogen bonding not possible incase of hydrocarbon. Among the nitro phenols we find that m-nitro phenol & p-nitro phenol having higher B.P. than o-nitro phenol why? Because, in m-nitro phenol & p-nitro phenol show molecular association due to intermolecular hydrogen bonding. But o-nitro phenol intramoleculr hydrogen bonding is present therefore molecular association is weak.

Preparation of phenols: a) From cumene hydro peroxide: Cumene can be obtained from benzene & propene by Friedel Craft alkylation reaction as below.

When cumene on air oxidation at high temp. gives cumene hydroperoxide which on

treatment with 10% H2SO4 we get phenol & acetone.

b) From Diazonium salts:

First Diazonium salt is prepared from aromatic primary amine & NaNO2+HCl. Then Diazonium salt on hydrolysis with water gives phenol.

Reactions of phenol: Phenol undergoes electrophilic substitution reactions. Hydroxyl group (-OH) of phenol is electron donating group (activating group). Therefore ortho & para positions of phenol becomes electron rich. Hence electrophilic substitution takes place at ortho & para positions. Ortho product formed as a minor % because at ortho position more steric crowding. Following are certain electrophilic substitution reactions of phenol. 1. Nitration of phenol:

A) With dil. HNO3: Phenol treated with dil. HNO3 it gives o-nitrophenol (minor) & p- nitrophenol (major) products. OH OH OH

Dil. HNO3 NO2 200 C +

p-nitrophenol Phenol o-nitrophenol NO2

B) With conc. HNO3: Phenol reacts with conc. HNO3 after nitration we get Polysubstituted products. OH OH OH

O N NO NO 2 2 Dil. HNO3 2 200 C +

Phenol NO2 NO2 2,4,6-trinitrophenol 2,4-dinitrophenol ( Picric acid)

2. Sulphonation : Phenol on sulphonation in presence of conc. H3SO4 it gives o- phenol sulphonic acid & p-phenol sulphonic acid. At room temp. Sulphonation takes place at ortho position but at high temp. gives para product.

At 100 0 C o- phenol sulphonic acid is isomerise to p-phenol sulphonic acid. 3. Halogenation of phenol:

A) With Br2 water: Phenol reacts with Br2 in water (polar solvent) it gives 2,4,6-tribromophenol. OH OH

3Br2 Br Br Water i.e.polar + 3 HBr

Phenol Br 2,4,6-tribromophenol B) With Br2 / CCl4 : Phenol reacts with Br2 in CCl4 (non-polar solvent) it gives o-bromophenol & p- bromophenol. OH OH OH

3Br2 Br CCl4 (non-polar) + + 2 HBr

Phenol o-bromophenol p-bromophenol Br 0 4) Nitrosation: Phenol reacts with NaNO2 + H2SO4 at 5 C nitrosation takes place at para position to form p-nitrosophenol. Sodium nitrite & sulphuric acid form nitrous acid (HNO2) & this nitrous acid is used for nitrosation in the reaction.

OH OH

NaNO2 + H2SO4 + HO-N=O + H2O Nitrous acid 5 0 C

Phenol N=O p-nitrosophenol 5) Carbonation of phenol (Kolbe synthesis):

By using Kolbe synthesis reaction we can prepare salicylic acid from phenol. When sodium phenoxide is treated with CO2 () at high temp. & pressure first we get sodium salicylate further which on acidification gives Salicylic acid (o-hydroxy benzoic acid).

OH ONa O O

H+ COOH acid 125 0 C ONa O C O Pressure H

Salicylic acid Sodium salicylate Sodium phenoxide Sodium phenoxide salt is prepared from phenol + NaOH.

6) Reimer-Tiemann Reaction:

In Reimer Tiemann reaction phenol is converted into salicyaldehyde (o-hydroxy benzaldehyde). Phenol is treated with chloroform in NaOH (basic medium) giving salicyaldehyde. From chloroform Dichlorocarbene is generates & which acts as an electrophile in this reaction.

7) Friedel-Craft Reactions:

Phenols & anilines do not undergo Friedel Craft reactions because –OH group of phenol

& (–NH2 gr. of anilines) coordinates (complex) with Lewis acid which deactivate the aromatic ring & hence alkylation or acylation not takes place incase of phenols & anilines.

OH H O AlCl3

AlCl3 R-X R-X AlCl3 No reaction F.C.alkylation

Ring is deactivated due to charged complex Phenol But if –OH gr. of phenol is converted into –OR then Friedel Craft reactions possible (Because deactivation of ring not possible) & gives major para product. CH OH O 3 OCH3 OCH3

1. NaOH CH3 CH3X 2. CH3-X AlCl3 +

Phenol Anisole Minor CH3 Major 8) Gattermann Reaction:

In Gattermann reaction phenol is treated with mixture of HCl & HCN in presence of

AlCl3 as a catalyst to gives salicyldehyde.

OH OH OH

CHO 1. HCN / HCl AlCl3 + 2. H2O

Salicyldehyde p-hydroxybenzaldehyde Phenol (o-hydroxybenzaldehyde) CHO Mechanism: In first step HCl + HCN forms imidoformyl chloride, which is then reacts with phenol to form imine. Imine on hydrolysis gives salicyldehyde.

9) Houben-Hoesch condensation:

From this reaction we can prepare aryl ketone from phenol. In this reaction dihydric phenol e.g. resorcinol is treated with methyl cyanide in HCl / AlCl3. OH OH OH

HCl AlCl3 H2O + CH3CN Reflux OH OH OH Resorcinol H3C O NH.HCl H3C Imine intermediate Aryl ketone Mechanism;

First alkyl cyanide complex with AlCl3 then nucleophilic addition of phenol to polarize complex to get imine finally on hydrolysis gives Aryl ketone i.e. 2, 4- dihydroxyacetophenone.

10) Schotten-Baumann reaction:

Phenols treated with benzoyl chloride in presence of NaOH gives benzoyl ester. e.g.