Structure and Synthesis of Alcohols

Structure of Alcohols Hydroxyl (OH) functional group Oxygen is sp3 hybridized. =>

Classification Primary: carbon with –OH 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 (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 =>

(1997 revision of IUPAC rules) => Unsaturated Alcohols Hydroxyl group takes precedence. Assign that carbon the lowest number. Use alkene or alkyne name. 4-penten-2-ol (old) pent-4-ene-2-ol (1997 revision of IUPAC rules) =>

Naming Priority Acids Esters Aldehydes Ketones Alcohols Amines Alkenes Alkynes Alkanes Ethers Halides =>

Hydroxy Substituent When -OH is part of a higher priority class of compound, it is named as hydroxy. Example: also known as GHB => 4-hydroxybutanoic acid

Common Names Alcohol can be named as alkyl alcohol. Useful only for small alkyl groups. Examples: isobutyl alcohol sec-butyl alcohol =>

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 -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. =>

Boiling Points =>

Solubility in Water Solubility decreases as the size of the alkyl group increases. =>

Methanol “Wood alcohol” Industrial production from synthesis gas Common industrial solvent Fuel at Indianapolis 500 Fire can be extinguished with water High octane rating Low emissions But, lower energy content Invisible flame =>

Ethanol Fermentation of sugar and starches in grains 12-15% alcohol, then yeast cells die. Distillation produces “hard” liquors Azeotrope: 95% ethanol, constant boiling Denatured alcohol used as solvent Gasahol: 10% ethanol in gasoline Toxic dose: 200 mL ethanol, 100 mL methanol =>

2-Propanol “Rubbing alcohol” Catalytic hydration of propene =>

Acidity of Alcohols pKa range: 15.5-18.0 (water: 15.7) Acidity decreases as alkyl group increases. Halogens increase the acidity. Phenol is 100 million times more acidic than cyclohexanol! =>

Table of Ka Values =>

Formation of Alkoxide Ions React methanol and ethanol with sodium metal (redox reaction). React less acidic alcohols with more reactive potassium. =>

Synthesis (Review) Nucleophilic substitution of OH- on alkyl halide Hydration of alkenes water in acid solution (not very effective) oxymercuration - demercuration hydroboration - oxidation =>

Organometallic Reagents Carbon is bonded to a metal (Mg or Li). Carbon is nucleophilic (partially negative). It will attack a partially positive carbon. C - X C = O A new carbon-carbon bond forms. =>

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

Some Grignard Reagents =>

Organolithium Reagents Formula R-Li (reacts like R:- +Li) Can be produced from alkyl, vinyl, or aryl halides, just like Grignard reagents. Ether not necessary, wide variety of solvents can be used. =>

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… =>

Grignard Reactions with Acid Chlorides and Esters Use two moles of Grignard reagent. The product is a tertiary alcohol with two identical alkyl groups. Reaction with one mole of Grignard reagent produces a ketone intermediate, which reacts with the second mole of Grignard reagent. =>

Grignard + Acid Chloride (1) Grignard attacks the carbonyl. Chloride ion leaves. Ketone intermediate =>

Grignard and Ester (1) 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 acid chloride or ester. =>

Grignard Reagent + Ethylene Oxide Epoxides are unusually reactive ethers. Product is a 1º alcohol with 2 additional carbons. =>

Limitations of Grignard No water or other acidic protons like O-H, N-H, S-H, or -C—C-H. Grignard reagent is destroyed, becomes an alkane. No other electrophilic multiple bonds, like C=N, C—N, S=O, or N=O. =>

Reduction of Carbonyl Reduction of aldehyde yields 1º alcohol. Reduction of ketone yields 2º alcohol. Reagents: Sodium borohydride, NaBH4 Lithium aluminum hydride, LiAlH4 Raney nickel =>

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. =>

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

Catalytic Hydrogenation Add H2 with Raney nickel catalyst. Also reduces any C=C bonds. =>

Thiols (Mercaptans) Sulfur analogues of alcohols, -SH. Named by adding -thiol to alkane name. The -SH group is called mercapto. Complex with heavy metals: Hg, As, Au. More acidic than alcohols, react with NaOH to form thiolate ion. Stinks! =>

Thiol Synthesis Use a large excess of sodium hydrosulfide with unhindered alkyl halide to prevent dialkylation to R-S-R. =>

Thiol Oxidation Easily oxidized to disulfides, an important feature of protein structure. Vigorous oxidation with KMnO4, HNO3, or NaOCl, produces sulfonic acids. => Chapter 10