Organic Chemistry, 5th Edition L. G. Wade, Jr. Chapter 10 Structure and Synthesis of Alcohols Jo Blackburn Richland College, Dallas, TX Dallas County Community College District 2003, Prentice Hall Structure of Alcohols • Hydroxyl (OH) functional group • Oxygen is sp3 hybridized. => Chapter 10 2 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. => Chapter 10 3 Classify these: CH3 CH3 CH3 CH CH2OH CH3 C OH CH3 OH OH CH3 Chapter 10 CH CH2CH3 => 4 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. => Chapter 10 5 Name these: CH3 CH3 CH CH2OH 2-methyl-1-propanol OH CH3 CH CH2CH3 2-butanol CH3 CH3 OH C OH CH3 2-methyl-2-propanol Br CH3 3-bromo-3-methylcyclohexanol => Chapter 10 6 Unsaturated Alcohols • Hydroxyl group takes precedence. Assign that carbon the lowest number. • Use alkene or alkyne name. OH CH2 CHCH2CHCH3 4-penten-2-ol (old) pent-4-ene-2-ol (1997 revision of IUPAC rules) => Chapter 10 7 Naming Priority • • • • • • Acids Esters Aldehydes Ketones Alcohols Amines • • • • • Alkenes Alkynes Alkanes Ethers Halides => Chapter 10 8 Hydroxy Substituent • When -OH is part of a higher priority class of compound, it is named as hydroxy. • Example: OH CH2CH2CH2COOH also known as GHB 4-hydroxybutanoic acid => Chapter 10 9 Common Names • Alcohol can be named as alkyl alcohol. • Useful only for small alkyl groups. • Examples: CH3 CH3 CH CH2OH isobutyl alcohol OH CH3 CH CH2CH3 sec-butyl alcohol => Chapter 10 10 Naming Diols • Two numbers are needed to locate the two -OH groups. • Use -diol as suffix instead of -ol. OH HO 1,6-hexanediol => Chapter 10 11 Glycols • 1, 2 diols (vicinal diols) are called glycols. • Common names for glycols use the name of the alkene from which they were made. CH2CH2 CH2CH2CH3 OH OH OH OH 1,2-ethanediol 1,2-propanediol ethylene glycol propylene glycol Chapter 10 => 12 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. OH • Methyl phenols are cresols. OH H3C 4-methylphenol para-cresol Cl 3-chlorophenol meta-chlorophenol => Chapter 10 13 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. => Chapter 10 14 Boiling Points => Chapter 10 15 Solubility in Water Solubility decreases as the size of the alkyl group increases. Chapter 10 => 16 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 Chapter 10 => 17 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 => Chapter 10 18 2-Propanol • “Rubbing alcohol” • Catalytic hydration of propene CH2 CH CH2 + H2O 100-300 atm, 300°C catalyst CH3 CH CH3 OH => Chapter 10 19 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! => Chapter 10 20 Table of Ka Values CH3 OH => Chapter 10 21 Formation of Alkoxide Ions React methanol and ethanol with sodium metal (redox reaction). CH3CH2OH + Na CH3CH2O Na + 1/2 H2 React less acidic alcohols with more reactive potassium. (CH3)3C OH + (CH3)3CO K K + 1/2 H2 => Chapter 10 22 Formation of Phenoxide Ion Phenol reacts with hydroxide ions to form phenoxide ions - no redox is necessary. O O H + OH + HOH pKa = 15.7 pKa = 10 => Chapter 10 23 Synthesis (Review) • Nucleophilic substitution of OH- on alkyl halide • Hydration of alkenes water in acid solution (not very effective) oxymercuration - demercuration hydroboration - oxidation => Chapter 10 24 Glycols (Review) • Syn hydroxylation of alkenes osmium tetroxide, hydrogen peroxide cold, dilute, basic potassium permanganate • Anti hydroxylation of alkenes peroxyacids, hydrolysis => Chapter 10 25 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. => Chapter 10 26 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 => Chapter 10 27 Some Grignard Reagents Br + ether Mg Cl CH3CHCH2CH3 + Mg CH3C CH2 Br + Mg ether ether MgBr MgCl CH3CHCH2CH3 CH3C CH2 => MgBr Chapter 10 28 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. => Chapter 10 29 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. R C O R C O R C OH HOH Chapter 10 => 30 OH Synthesis of 1° Alcohols Grignard + formaldehyde yields a primary alcohol with one additional carbon. CH3 H3C C CH2 C H H CH3 H H MgBr C O CH3 CH CH2 H CH2 H MgBr H CH3 CH3 C O CH CH2 H CH2 HOH C O H H => Chapter 10 31 Synthesis of 2º Alcohols Grignard + aldehyde yields a secondary alcohol. CH3 H3C C CH2 C H H CH3 H3C H MgBr C O CH3 CH CH2 CH3 CH2 H MgBr H CH3 CH3 C O CH CH2 CH3 CH2 HOH C O H H => Chapter 10 32 Synthesis of 3º Alcohols Grignard + ketone yields a tertiary alcohol. CH3 H3C C CH2 C H H CH3 H3C H MgBr C O CH3 CH CH2 CH3 CH2 H3C MgBr CH3 CH3 CH3 C O CH CH2 CH3 CH2 HOH C O H CH3 => Chapter 10 33 How would you synthesize… OH CH2OH CH3CH2CHCH2CH2CH3 OH OH CH3 C CH3 CH2CH3 Chapter 10 => 34 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. => Chapter 10 35 Grignard + Acid Chloride (1) • Grignard attacks the carbonyl. • Chloride ion leaves. CH3 H3C R MgBr C O Cl CH3 R C O R C O MgBr Cl CH3 MgBr R C Cl + MgBrCl O Ketone intermediate Chapter 10 => 36 Grignard and Ester (1) • Grignard attacks the carbonyl. • Alkoxide ion leaves! ? ! CH3 H3C R MgBr C O R C O CH3O OCH3 CH3 R C O OCH3 MgBr CH3 MgBr R C + O MgBrOCH3 Ketone intermediate Chapter 10 => 37 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. CH3 CH3 R MgBr + R C R C O O MgBr R HOH CH3 R C OH R Chapter 10 => 38 How would you synthesize... Using an acid chloride or ester. OH CH3 CH3CH2CCH3 C CH3 OH OH CH3CH2CHCH2CH3 Chapter 10 => 39 Grignard Reagent + Ethylene Oxide • Epoxides are unusually reactive ethers. • Product is a 1º alcohol with 2 additional carbons. O O MgBr + CH2 MgBr CH2CH2 CH2 HOH O H CH2CH2 Chapter 10 => 40 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. => Chapter 10 41 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 => Chapter 10 42 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. O C H H C H H O + H H3O O H C H => Chapter 10 43 Lithium Aluminum Hydride • Stronger reducing agent than sodium borohydride, but dangerous to work with. • Converts esters and acids to 1º alcohols. O C OCH3 H LAH H3O+ Chapter 10 C O H H => 44 Comparison of Reducing Agents • LiAlH4 is stronger. • LiAlH4 reduces more stable compounds which are resistant to reduction. => Chapter 10 45 Catalytic Hydrogenation • Add H2 with Raney nickel catalyst. • Also reduces any C=C bonds. OH O OH H2, Raney Ni NaBH4 => Chapter 10 46 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! => Chapter 10 47 Thiol Synthesis Use a large excess of sodium hydrosulfide with unhindered alkyl halide to prevent dialkylation to R-S-R. _ H S _ R X R SH + X => Chapter 10 48 Thiol Oxidation • Easily oxidized to disulfides, an important feature of protein structure. Br2 R SH + HS R R S S R + 2 HBr Zn, HCl Vigorous oxidation with KMnO4, HNO3, or NaOCl, produces sulfonic acids. • SH HNO3 boil O S O Chapter 10 OH => 49 End of Chapter 10 Chapter 10 50