Chapter 17- Alcohols and Phenols Alcohols and Phenols Alcohols contain an OH group connected to a a saturated C (sp 3 ) They are important solvents and synthesis intermediates Phenols contain an OH group connected to a carbon in a benzene ring 1
Alcohols and Phenols Methanol, CH 3 OH, called methyl alcohol, is a common solvent, a fuel addigve, produced in large quangges Ethanol, CH 3 CH 2 OH, called ethyl alcohol, is a solvent, fuel, beverage Phenol, C 6 H 5 OH ( phenyl alcohol ) has diverse uses - it gives its name to the general class of compounds OH groups bonded to vinylic, sp 2 -hybridized carbons are called enols Why do I care, Dr. P? To begin to study oxygen-containing funcgonal groups These groups lie at the heart of biological chemistry 2
Nomenclature General classificagons of alcohols based on subsgtugon on C to which OH is apached Methyl (C has 3 H s), Primary (1 ) (C has two H s, one R), Secondary (2 ) (C has one H, two R s), TerGary (3 ) (C has no H, 3 R s), IUPAC Rules for Naming Alcohols 1) Select the longest carbon chain containing the hydroxyl group, and derive the parent name by replacing the -e ending of the corresponding alkane with -ol 2) Number the chain from the end nearer the hydroxyl group 3) Number subsgtuents according to posigon on chain, lisgng the subsgtuents in alphabegcal order 3
Naming Phenols Use phenol (the French name for benzene) as the parent hydrocarbon name, not benzene Name subsgtuents on aromagc ring by their posigon from OH Learning check Give the correct IUPAC names for the following compounds. OH Cl O 2 N HO H 4
Properties of Alcohols and Phenols The structure around O of the alcohol or phenol is similar to that in water, sp 3 hybridized Alcohols and phenols have much higher boiling points than similar alkanes and alkyl halides Why do you think alcohols and phenols have high boiling points? Properties of Alcohols and Phenols: Acidity and Basicity Weakly basic and weakly acidic Alcohols are weak Brønsted bases Protonated by strong acids to yield oxonium ions, ROH 2 + 5
Alcohols and Phenols are Weak Brønsted Acids Can transfer a proton to water to a very small extent Produces H 3 O + and an alkoxide ion, RO -, or a phenoxide ion, ArO - Acidity Measurements The acidity constant, K a, measures the extent to which a Brønsted acid transfers a proton to water [A - ] [H 3 O + ] K a = and pk a = -log K a [HA] RelaGve acidiges are more conveniently presented on a logarithmic scale, pk a, which is directly proporgonal to the free energy of the equilibrium What is the relagonship between pk a and the strength of the acid? Differences in pk a correspond to differences in free energy 6
pk a Values for Typical OH Compounds Relative Acidities of Alcohols Simple alcohols are about as acidic as water Alkyl groups make an alcohol a weaker acid The more easily the alkoxide ion is solvated by water the more its formagon is energegcally favored 7
Inductive Effects Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide) Generating Alkoxides from Alcohols Alcohols are weak acids requires a strong base to form an alkoxide such as NaH, sodium amide NaNH 2, and Grignard reagents (RMgX) Alkoxides are bases used as reagents in organic chemistry 8
Phenol Acidity Phenols (pk a ~10) are much more acidic than alcohols (pk a ~ 16) due to resonance stabilizagon of the phenoxide ion Phenols react with NaOH solugons (but alcohols do not), forming salts that are soluble in dilute aqueous solugon Why is this important in the laboratory? Nitro-Phenols Phenols with nitro groups at the ortho and para posigons are much stronger acids 9
Learning check The following data for isomeric four-carbon alcohols show that there is a decrease in boiling point with increasing subsgtugon of the OH-bearing carbon. How might you account for this trend? 1-butanol, bp 117.5 C 2-butanol, bp 99.5 C 2-methyl-2-propanol, bp 82.2 C Preparation of Alcohols: A Review Alcohols are derived from many types of compounds The alcohol can be converted to many other funcgonal groups 10
Preparation of Alcohols What are some ways you can prepare alcohols from alkenes? Review: Preparation of Alcohols by Regiospecific Hydration of Alkenes HydroboraGon/oxidaGon: syn, non-markovnikov hydragon OxymercuraGon/reducGon: Markovnikov hydragon 11
1,2-Diols Cis-1,2-diols from hydroxylagon of an alkene with OsO 4 followed by reducgon with NaHSO 3 Trans-1,2-diols from acid-catalyzed hydrolysis of epoxides Learning check Predict the products of the following reacgons: 1. OsO 4, pyridine 2. NaHSO 3, H 2 O 1. Hg(OAc) 2, H 2 O 2. NaBH 4 12
Alcohols from Reduction of Carbonyl Compounds ReducGon of a carbonyl compound in general gives an alcohol Note that organic reducgon reacgons add the equivalent of H 2 to a molecule Reduction of Aldehydes and Ketones Aldehydes produce primary alcohols Ketones produce secondary alcohols 13
Reducing Reagent: Sodium Borohydride NaBH 4 is not sensigve to moisture and it does not reduce other common funcgonal groups Lithium aluminum hydride (LiAlH 4 ) is more powerful, less specific, and very reacgve with water 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 14
Reduction of Carboxylic Acids and Esters Carboxylic acids and esters are reduced to give primary alcohols LiAlH 4 is used because NaBH 4 is not effecgve Alcohols from Reaction of Carbonyl Compounds with Grignard Reagents Alkyl, aryl, and vinylic halides react with magnesium in ether or tetrahydrofuran to generate Grignard reagents, RMgX Grignard reagents react with carbonyl compounds to yield alcohols 15
Reactions of Grignard Reagents with Carbonyl Compounds Reactions of Esters and Grignard Reagents Yields tergary alcohols in which two of the subsgtuents come from the Grignard reagent Grignard reagents do not add to carboxylic acids they undergo an acid-base reacgon, generagng the hydrocarbon of the Grignard reagent 16
Grignard Reagents and Other Functional Groups in the Same Molecule Can't be prepared if there are reacgve funcgonal groups in the same molecule, including proton donors Mechanism of the Addition of a Grignard Reagent Grignard reagents act as nucleophilic carbon anions (carbanions, : R-) in adding to a carbonyl group The intermediate alkoxide is then protonated to produce the alcohol 17
Learning check Predict the product of the following reacgons below. MgBr + O 1. ether 2. H 3 O + O OH 1. LiAlH 4, ether 2. H 3 O + Reactions of Alcohols Conversion of alcohols into alkyl halides: - 3 alcohols react with HCl or HBr by S N 1 through carbocagon intermediate - 1 and 2 alcohols converted into halides by treatment with SOCl 2 or PBr 3 via S N 2 mechanism 18
Conversion of Alcohols into Tosylates ReacGon with p-toluenesulfonyl chloride (tosyl chloride, p-toscl) in pyridine yields alkyl tosylates, ROTos FormaGon of the tosylate does not involve the C O bond so configuragon at a chirality center is maintained Alkyl tosylates react like alkyl halides 19
Stereochemical Uses of Tosylates The S N 2 reacgon of an alcohol via a tosylate, produces inversion at the chirality center The S N 2 reacgon of an alcohol via an alkyl halide proceeds with two inversions, giving product with same arrangement as stargng alcohol Dehydration of Alcohols to Yield Alkenes The general reacgon: forming an alkene from an alcohol through loss of O-H and H (hence dehydragon) of the neighboring C H to give π bond 20
Acid- Catalyzed Dehydration TerGary alcohols are readily dehydrated with acidwhy is 2-methyl-2-butene the major product? Secondary alcohols require severe condigons (75% H 2 SO 4, 100 C) - sensigve molecules don't survive Primary alcohols require very harsh condigons impracgcal ReacGvity is the result of the nature of the carbocagon intermediate 21
Dehydration with POCl 3 Phosphorus oxychloride in the amine solvent pyridine can lead to dehydragon of secondary and tergary alcohols at low temperatures An E2 via an intermediate ester of POCl 2 22
Conversion of Alcohols into Esters Learning check Predict the product for the following reacgon below. H OH 1. p-toscl, pyridine 2. NaOCH 3, CH 3 OH 23
Oxidation of Alcohols Can be accomplished by inorganic reagents, such as KMnO 4, CrO 3, and Na 2 Cr 2 O 7 or by more selecgve, expensive reagents Oxidation of Primary Alcohols To aldehyde: pyridinium chlorochromate (PCC, C 5 H 6 NCrO 3 Cl) in dichloromethane Other reagents produce carboxylic acids 24
Oxidation of Secondary Alcohols EffecGve with inexpensive reagents such as Na 2 Cr 2 O 7 in acegc acid PCC is used for sensigve alcohols at lower temperatures Mechanism of Chromic Acid Oxidation Alcohol forms a chromate ester followed by eliminagon with electron transfer to give ketone The mechanism was determined by observing the effects of isotopes on rates 25
Protection of Alcohols Hydroxyl groups can easily transfer their proton to a basic reagent This can prevent desired reacgons ConverGng the hydroxyl to a (removable) funcgonal group without an acidic proton protects the alcohol Methods to Protect Alcohols ReacGon with chlorotrimethylsilane in the presence of base yields an unreacgve trimethylsilyl (TMS) ether The ether can be cleaved with acid or with fluoride ion to regenerate the alcohol 26
Protection-Deprotection An example of TMS-alcohol protecgon in a synthesis Reactions of Phenols The hydroxyl group is a strongly acgvagng, making phenols substrates for electrophilic halogenagon, nitragon, sulfonagon, and Friedel Crats reacgons ReacGon of a phenol with strong oxidizing agents yields a quinone Fremy's salt [(KSO 3 ) 2 NO] works under mild condigons through a radical mechanism 27
Quinones in Nature Ubiquinones mediate electron-transfer processes involved in energy producgon through their redox reacgons Spectroscopy of Alcohols and Phenols CharacterisGc O H stretching absorpgon at 3300 to 3600 cm -1 in the infrared Sharp absorpgon near 3600 cm -1 except if H-bonded: then broad absorpgon 3300 to 3400 cm -1 range Strong C O stretching absorpgon near 1050 cm -1 Phenol OH absorbs near 3500 cm -1 28
IR spectrum 29
Nuclear Magnetic Resonance Spectroscopy 13 C NMR: C bonded to OH absorbs at a lower field, δ 50 to 80 1 H NMR: electron-withdrawing effect of the nearby oxygen, absorbs at δ 3.5 to 4 (See Figure 17-13) Usually no spin-spin coupling between O H proton and neighboring protons on C due to exchange reacgons with moisture or acids Spin spin spliung is observed between protons on the oxygen-bearing carbon and other neighbors Phenol O H protons absorb at δ 3 to 8 NMR spectrum 30
Mass Spectrometry Alcohols undergo alpha cleavage, a C C bond nearest the hydroxyl group is broken, yielding a neutral radical plus a charged oxygen-containing fragment Alcohols undergo dehydragon to yield an alkene radical anion Mass Spectrum 31