Chapter 8 of Alcohols and Phenols

Structure of Alcohols Alcohols are simply organic derivatives of water formed by replacing one H of water with an R group. All alcohols have the hydroxyl (OH) functional group

Classification of Alcohols Alcohols are classified as primary, secondary, tertiary or aromatic depending upon the class of the alcoholic carbon Primary: carbon with –OH (alcoholic carbon) is bonded to one other carbon. Secondary: carbon with –OH is bonded to two other carbons. Tertiary: carbon with –OH is bonded to three other carbons. Aromatic Alcohol (phenol): -OH is bonded to a benzene ring. =>

Classify these: =>

IUPAC Nomenclature Find the longest carbon chain containing the carbon with the -OH group. Drop the -e from the alkane name, add -ol. Number the chain, starting from the end closest to the -OH group. Number and name all substituents. =>

Name these: 2-methyl-1-propanol 2-butanol 2-methyl-2-propanol 3-bromo-3-methylcyclohexanol =>

Naming Diols Two numbers are needed to locate the two -OH groups. Use -diol as suffix instead of -ol. 1,6-hexanediol =>

Glycols 1, 2 diols (vicinal diols) are called glycols. Common names for glycols use the name of the alkene from which they were made. 1,2-ethanediol 1,2-propanediol ethylene glycol propylene glycol =>

Naming Phenols (Aromatic Alcohols) -OH group is assumed to be on carbon 1. For common names of disubstituted phenols, use ortho- for 1,2; meta- for 1,3; and para- for 1,4. Methyl phenols are cresols. 4-methylphenol para-cresol => 3-chlorophenol meta-chlorophenol

Physical Properties Unusually high boiling points due to hydrogen bonding between molecules. Small alcohols are miscible in water, but solubility decreases as the size of the alkyl group increases. =>

The High Boiling Points of Alcohols and Phenols are due to their ability to Hydrogen Bond to one another Alcohols and phenols have much higher boiling points than other molecules of similar Molecular Weight

Alcohols Form Hydrogen Bonds A positively polarized OH hydrogen atom from one molecule is attracted to a lone pair of electrons on a negatively polarized oxygen atom of another molecule This produces a force that holds the two molecules together These intermolecular attractions are present in solution but not in the gas phase, thus elevating the boiling point of the solution

Solubility in Water Solubility decreases as the size of the alkyl group increases. => Polar Non-polar

Alchols and Phenols are Weak Brønsted Acids Remember, Bronsted Acids are Proton Donars. Alcohols and Phenols can donate a proton to water The products are H3O+ and an alkoxide anion, RO, or a phenoxide anion, ArO

Relative Acidities of Alcohols and Steric Effects Alkyl groups make an alkoxide anion more difficult to be solvated and stabilized by water molecules and therefore make its formation less likely and the corresponding acid necessarily weaker The more easily the alkoxide ion is solvated by water the more stable it is and the more its formation is energetically favored Less likely to form More likely to form

Inductive Effects Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the alkoxide anion

Table of Ka Values =>

Generating Alkoxides from Alcohols As weak acids, alcohols react with strong bases like sodium or potassium metal to generate alkoxides Alkoxides are bases used as reagents in organic chemistry

Formation of Phenoxide Ion Phenol is more acidic than regular alcohols because the phenoxide anion is resonance stabilized. Electron withdrawing groups stabilize the phenoxide anion and make phenol more acidic Consequently, phenol can be deprotonated by a simple hydroxy base. O H O + O H + H O H p K = 1 5 . 7 a p K = 1 a =>

Substituted Phenols Can be more or less acidic than phenol itself. Remember, the acidity of any alcohol is determined by the stability of the alkoxide or phenoxide anion produced. The more stable the anion produced the more acidic the alcohol An electron-withdrawing substituent makes a phenol more acidic by delocalizing the negative charge on the phenoxide anion Phenols with an electron-donating substituent are less acidic because these substituents concentrate the charge

Preparation of Alchols: an Overview Alcohols are derived from many types of compounds Also the alcohol hydroxyl can be converted into many other functional groups This makes alcohols useful in synthesis

Review: Preparation of Alcohols from Alkenes Markovnikov and Anti-Mardovnikov hydration H2SO4

Alcohols from Reduction of Carbonyl Compounds Reduction of a carbonyl compound in general gives an alcohol Note that organic reduction reactions increase the C-H bonds and/or decrease the C-O bonds 1.H- 2.H+

Reduction of Aldehydes and Ketones Aldehydes gives primary alcohols Ketones gives secondary alcohols 1.H- 2.H+ 1.H- 2.H+

Reducing agents: Sodium Borohydride and Lithium Aluminum Hydride, Sources of H- NaBH4 is safe, not sensitive to moisture, and it does not reduce other common functional groups Lithium aluminum hydride (LiAlH4) is more powerful, will reduce species that NaBH4 will not, but is dangerous to use Both add the equivalent of “H-”

Mechanism of Reduction The reagent adds the equivalent of hydride to the carbon of C=O and polarizes the group as well

Reduction of Carboxylic Acids and Esters Carboxylic acids and esters are reduced to give primary alcohols LiAlH4 is used because NaBH4 is not effective

Sodium Borohydride Hydride ion, H-, attacks the carbonyl carbon, forming an alkoxide ion. Then the alkoxide ion is protonated by dilute acid. Only reacts with carbonyl of aldehyde or ketone, not with carbonyls of esters or carboxylic acids. =>

Lithium Aluminum Hydride Stronger reducing agent than sodium borohydride, but dangerous to work with. Converts esters and acids to 1º alcohols. =>

LiAlH4 Reactions with Esters and Carboxylate Anions Use two moles of Hydride (H-) reagent. The product is a primary alcohol with two hydrogens from hydride reagent. Reaction with the first mole of Hydride reagent produces an aldehyde intermediate, which reacts with the second mole of Hydride =>

LiAlH4 and Ester – Step 1 The first hydride (H-) attacks the carbonyl. Alkoxide ion leaves! ? ! H H- Alkoxide H H + CH3O- Aldehyde intermediate =>

Second step of reaction The second hydride reacts with the aldehyde intermediate to form an alkoxide ion. Alkoxide ion is protonated with water or dilute acid. H H- H H- H => + H H H

Comparison of Reducing Agents LiAlH4 is stronger. LiAlH4 reduces more stable compounds which are resistant to reduction. =>

Organometallic Reagents Carbon is bonded to a metal (Mg) Carbon is more electronegative than the metal and therefore is nucleophilic (partially negative). It will attack a partially positive carbon. C = O in much the same way as the H- A new carbon-carbon bond forms and a more complex alcohol is formed. =>

Grignard Reagents Formula R-Mg-X (reacts like R:- +MgX) Stabilized by anhydrous ether May be formed from any halide primary secondary tertiary vinyl aryl =>

Some Grignard Reagent Formations =>

Reaction with Carbonyl R:- attacks the partially positive carbon in the carbonyl. The intermediate is an alkoxide ion. Addition of water or dilute acid protonates the alkoxide to produce an alcohol. =>

Synthesis of 1° Alcohols Grignard + formaldehyde yields a primary alcohol with one additional carbon. =>

Synthesis of 2º Alcohols Grignard + aldehyde yields a secondary alcohol. =>

Synthesis of 3º Alcohols Grignard + ketone yields a tertiary alcohol. =>

How would you synthesize these using a Grignard Reagent… =>

Grignard Reactions with Esters Use two moles of Grignard attack. Just as two moles of Hydride attacked an Ester. The product is a tertiary alcohol with two identical alkyl groups ( from Grignard). Reaction with one mole of Grignard reagent produces a ketone intermediate, which reacts with the second mole of Grignard reagent. =>

Grignard and Ester – First Step Grignard attacks the carbonyl. Alkoxide ion leaves! ? ! Ketone intermediate =>

Second step of reaction Second mole of Grignard reacts with the ketone intermediate to form an alkoxide ion. Alkoxide ion is protonated with dilute acid. =>

How would you synthesize... Using an ester. =>

Some Reactions of Alcohols Two general classes of reaction At the carbon of the C–O bond At the proton of the O–H bond

Dehydration of Alcohols to Yield Alkenes The general reaction: forming an alkene from an alcohol through loss of O-H and H (hence dehydration) of the neighboring C–H to give  bond Specific reagents are needed

Acid- Catalyzed Dehydration Tertiary alcohols are readily dehydrated with acid Secondary alcohols require more severe conditions (75% H2SO4, 100°C) - sensitive molecules don't survive Primary alcohols require very harsh conditions – impractical Reactivity order is the result of the stability order of the carbocation intermediate

Dehydration with POCl3 Phosphorus oxychloride in the amine solvent pyridine can lead to dehydration of secondary and tertiary alcohols at low temperatures

Conversion of Alcohols into Alkyl Halides 3° alcohols are converted by HCl or HBr at low temperature (Figure 17.7) 1° and 2 ° alcohols are resistant to acid – use SOCl2 or PBr3 by an SN2 mechanism

Oxidation of Alcohols This can be accomplished by a wide range of inorganic oxidizing agents, such as KMnO4, CrO3, and Na2Cr2O7 Remember oxidation in Organic Chem refers to any reaction that adds bonds from carbon to oxygen and/or removes bonds from carbon to hydrogen

Oxidation of Primary Alcohols To aldehyde: pyridinium chlorochromate (PCC) in dichloromethane Other reagents produce carboxylic acids

Oxidation of Secondary Alcohols Effective with inexpensive reagents such as Na2Cr2O7 in acetic acid or CrO3 in H2SO4 (Jones Reagent)

Laboratory Preparation of Phenols From aromatic sulfonic acids by melting with NaOH at high temperature Limited to the preparation of alkyl-substituted phenols

Reactions of Phenols Phenols take part in electrophilic aromatic substitution reactions. The OH group is an ortho para activating group so phenol readily substitute the following in the ortho and para positions: Br using Br2/FeBr3 NO2 using HNO3/H2SO4 SO3H using SO3/H2SO4