Chapter 11 Alcohols and phenols

IUPAC Substitutive Nomenclature An IUPAC name may have up to 4 features: locants, prefixes, parent compound and suffixes Numbering generally starts from the end of the chain which is closest to the group named in the suffix IUPAC Nomenclature of Alcohols Select the longest chain containing the hydroxyl and change the suffix name of the corresponding parent alkane from -ane to -ol Number the parent to give the hydroxyl the lowest possible number The other substituents take their locations accordingly Chapter 4

Examples Common Names of simple alcohols are still often used and are approved by IUPAC Chapter 4

Alcohols with two hydroxyls are called diols in IUPAC nomenclature and glycols in common nomenclature Chapter 4

Physical Properties of Alcohols. Alcohols have considerably higher boiling points Molecules of alcohols hydrogen bond to each other alcohols can hydrogen bond to water and have similar solubilities in water 1-butanol have solubilites of about 8 g per 100 mL in water Chapter 11

Synthesis of Alcohols from Alkenes Acid-Catalyzed Hydration of Alkenes This is a reversible reaction with Markovnikov regioselectivity Oxymercuration-demercuration This is a Markovnikov addition which occurs without rearrangement Chapter 11

Hydroboration-Oxidation This addition reaction occurs with anti-Markovnikov regiochemistry and syn stereochemistry Chapter 11

Alcohols by Reduction of Carbonyl Compounds A variety of carbonyl compounds can be reduced to alcohols Carboxylic acids can be reduced to primary alcohols These are difficult reductions and require the use of powerful reducing agents such as lithium aluminum hydride (LiAlH4 also abbreviated LAH) Chapter 12

Esters are also reduced to primary alcohols LAH or high pressure hydrogenation can accomplish this transformation Aldehydes and ketones are reduced to 1o and 2o alcohols respectively Aldehydes and ketones are reduced relatively easily; the mild reducing agent sodium borohydride (NaBH4) is typically used LAH and hydrogenation with a metal catalyst can also be used Chapter 12

The key step in the reduction is reaction of hydride with the carbonyl carbon Carboxylic acids and esters are considerably less reactive to reduction than aldehydes and ketones and require the use of LAH Lithium aluminium hydride is very reactive with water and must be used in an anhydrous solvent such as ether Sodium borohydride is considerably less reactive and can be used in solvents such as water or an alcohol Chapter 12

Reaction of Grignard Reagents with Carbonyl Compounds Nucleophilic attack of Grignard reagents at carbonyl carbons is the most important reaction of Grignard reagents Reaction of Grignard reagents with aldehydes and ketones yields a new carbon-carbon bond and an alcohol Chapter 12

Alcohols from Grignard Reagents Aldehydes and ketones react with Grignard reagents to yield different classes of alcohols depending on the starting carbonyl compound Chapter 12

Esters react with two molar equivalents of a Grignard reagent to yield a tertiary alcohol A ketone is formed by the first molar equivalent of Grignard reagent and this immediately reacts with a second equivalent to produce the alcohol The final product contains two identical groups at the alcohol carbon that are both derived from the Grignard reagent Chapter 12

Chapter 12

Alcohols as Acids Alcohols have acidities similar to water Sterically hindered alcohols such as tert-butyl alcohol are less acidic (have higher pKa values) Why?: The conjugate base is not well solvated and so is not as stable Alcohols are stronger acids than terminal alkynes and primary or secondary amines An alkoxide can be prepared by the reaction of an alcohol with sodium or potassium metal Chapter 11

Conversion of Alcohols into Alkyl Halides Hydroxyl groups are poor leaving groups, and as such, are often converted to alkyl halides when a good leaving group is needed Three general methods exist for conversion of alcohols to alkyl halides, depending on the classification of the alcohol and the halogen desired Reaction can occur with phosphorus tribromide, thionyl chloride or hydrogen halides Chapter 11

Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides The order of reactivity is as follows Hydrogen halide HI > HBr > HCl > HF Type of alcohol 3o > 2o > 1o < methyl Mechanism of the Reaction of Alcohols with HX SN1 mechanism for 3o, 2o, allylic and benzylic alcohols These reactions are prone to carbocation rearrangements In step 1 the hydroxyl is converted to a good leaving group In step 2 the leaving group departs as a water molecule, leaving behind a carbocation Chapter 11

Primary and methyl alcohols undergo substitution by an SN2 mechanism In step 3 the halide, a good nucleophile, reacts with the carbocation Primary and methyl alcohols undergo substitution by an SN2 mechanism Primary and secondary chlorides can only be made with the assistance of a Lewis acid such as zinc chloride Chapter 11

Alkyl Halides from the Reaction of Alcohols with PBr3 and SOCl2 These reagents only react with 1o and 2o alcohols in SN2 reactions In each case the reagent converts the hydroxyl to an excellent leaving group No rearrangements are seen Reaction of phosphorous tribromide to give alkyl bromides Chapter 11

Oxidation of Alcohols Oxidation of Primary Alcohols to Aldehydes A primary alcohol can be oxidized to an aldehyde or a carboxylic acid The oxidation is difficult to stop at the aldehyde stage and usually proceeds to the carboxylic acid A reagent which stops the oxidation at the aldehyde stage is pyridinium chlorochromate (PCC) PCC is made from chromium trioxide under acidic conditions It is used in organic solvents such as methylene chloride (CH2Cl2) Chapter 12

Oxidation of Primary Alcohols to Carboxylic Acids Potassium permanganate (KMnO4) is a typical reagent used for oxidation of a primary alcohol to a carboxylic acid The reaction is generally carried out in aqueous solution; a brown precipitate of MnO2 indicates that oxidation has taken place Oxidation of Secondary Alcohols to Ketones Oxidation of a secondary alcohol stops at the ketone Many oxidizing agents can be used, including chromic acid (H2CrO4) and Jones reagent (CrO3 in acetone) Chapter 12

Structure and Nomenclature of Phenols Phenols have hydroxyl groups bonded directly to a benzene ring Naphthols and phenanthrols have a hydroxyl group bonded to a polycyclic benzenoid ring Chapter 21

Nomenclature of Phenols Phenol is the parent name for the family of hydroxybenzenes Methylphenols are called cresols Chapter 21

Synthesis of Phenols Laboratory Synthesis Phenols can be made by hydrolysis of arenediazonium salts Chapter 21

Industrial Syntheses 1. Hydrolysis of Chlorobenzene (Dow Process) Chlorobenzene is heated with sodium hydroxide under high pressure The reaction probably proceeds through a benzyne intermediate (Section 21.11B) 2. Alkali Fusion of Sodium Benzenesulfonate Sodium benzenesulfonate is melted with sodium hydroxide Chapter 21

Reactions of Phenols as Acids Strength of Phenols as Acids Phenols are much stronger acids than alcohols Chapter 21

Phenol is much more acidic than cyclohexanol Experimental results show that the oxygen of a phenol is more positive and this makes the attached hydrogen more acidic The oxygen of phenol is more positive because it is attached to an electronegative sp2 carbon of the benzene ring Resonance contributors to the phenol molecule also make the oxygen more positive Chapter 21

Distinguishing and Separating Phenols from Alcohols and Carboxylic Acids Phenols are soluble in aqueous sodium hydroxide because of their relatively high acidity Most alcohols are not soluble in aqueous sodium hydroxide A water-insoluble alcohol can be separated from a phenol by extracting the phenol into aqueous sodium hydroxide Phenols are not acidic enough to be soluble in aqueous sodium bicarbonate (NaHCO3) Carboxylic acids are soluble in aqueous sodium bicarbonate Carboxylic acids can be separated from phenols by extracting the carboxylic acid into aqueous sodium bicarbonate Chapter 21

Other Reactions of the O-H Group of Phenols Phenols can be acylated with acid chlorides and anhydrides Chapter 21

Phenols in the Williamson Ether Synthesis Phenoxides (phenol anions) react with primary alkyl halides to form ethers by an SN2 mechanism Chapter 21

Cleavage of Alkyl Aryl Ethers Reaction of alkyl aryl ethers with HI or HBr leads to an alkyl halide and a phenol Recall that when a dialkyl ether is reacted, two alkyl halides are produced Chapter 21

Reaction of the Benzene Ring of Phenols Bromination The hydroxyl group is a powerful ortho, meta director and usually the tribromide is obtained Monobromination can be achieved in the presence of carbon disulfide at low temperature Nitration Nitration produces o- and p-nitrophenol Low yields occur because of competing oxidation of the ring Chapter 21

Sulfonation Sulfonation gives mainly the the ortho (kinetic) product at low temperature and the para (thermodynamic) product at high temperature Chapter 21

The Kolbe Reaction Carbon dioxide is the electrophile for an electrophilic aromatic substitution with phenoxide anion The phenoxide anion reacts as an enolate The initial keto intermediate undergoes tautomerization to the phenol product Kolbe reaction of sodium phenoxide results in salicyclic acid, a synthetic precursor to acetylsalicylic acid (aspirin) Chapter 21