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Transcript
CH 17: Alcohols and Phenols Renee Y. Becker CHM 2211 Valencia Community College 1 Alcohols and Phenols • Alcohols contain an OH group connected to a saturated C (sp3) – They are important solvents and synthesis intermediates • Enols also contain an OH group connected to an unsaturated C (sp2) • Phenols contain an OH group connected to a carbon in a benzene ring OH an enol 2 Alcohols and Phenols • Methanol, CH3OH, called methyl alcohol, is a common solvent, a fuel additive, produced in large quantities • Ethanol, CH3CH2OH, called ethyl alcohol, is a solvent, fuel, beverage • Phenol, C6H5OH (“phenyl alcohol”) has diverse uses - it gives its name to the general class of compounds 3 Naming Alcohols • General classifications of alcohols based on substitution on C to which OH is attached 4 IUPAC Rules for Naming Alcohols • 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 • Number the chain from the end nearer the hydroxyl group • Number substituents according to position on chain, listing the substituents in alphabetical order 5 6 Many Alcohols Have Common Names • These are accepted by IUPAC 7 Example 1: Give the IUPAC names for these compounds OH OH 3 1 HO 2 OH OH 4 H 3C CH3 8 Example 2: Draw the following structures • 2-Ethyl-2-buten-1-ol • 3-Cyclohexen-1-ol • 1,4-Pentanediol 9 Naming Phenols • Use “phene” (the French name for benzene) as the parent hydrocarbon name, not benzene • Name substituents on aromatic ring by their position from OH 10 Properties of Alcohols and Phenols: Hydrogen Bonding • The structure around O of the alcohol or phenol is similar to that in water, sp3 hybridized • Alcohols and phenols have much higher boiling points than similar alkanes and alkyl halides 11 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 12 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, ROH2+ 13 Alchols and Phenols are Weak Brønsted Acids • Can transfer a proton to water to a very small extent • Produces H3O+ and an alkoxide ion, RO, or a phenoxide ion, ArO 14 15 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 formation is energetically favored • Steric effects are important 16 Stronger acid 17 Inductive Effects • Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide) Stronger acid 18 Generating Alkoxides from Alcohols • Alcohols are weak acids – requires a strong base to form an alkoxide such as NaH, sodium amide NaNH2, and Grignard reagents (RMgX) • Alkoxides are bases used as reagents in organic chemistry 19 1 2 3 Example 3: + CH3OH NaH + CH3CH2OH NaNH2 OH + 4 CH3Li OH + CH3MgBr 5 2 OH + 2K 20 Phenol Acidity • Phenols (pKa ~10) are much more acidic than alcohols (pKa ~ 16) due to resonance stabilization of the phenoxide ion • Phenols react with NaOH solutions (but alcohols do not), forming soluble salts that are soluble in dilute aqueous • A phenolic component can be separated from an organic solution by extraction into basic aqueous solution and is isolated after acid is added to the solution 21 Substituted Phenols • Can be more or less acidic than phenol itself • An electron-withdrawing substituent makes a phenol more acidic by delocalizing the negative charge • Phenols with an electron-donating substituent are less acidic because these substituents concentrate the charge 22 Example 4: p-Nitrobenzyl alcohol is more acidic than benzyl alcohol. Explain. OH OH O2N 23 Nitro-Phenols • Phenols with nitro groups at the ortho and para positions are much stronger acids • The pKa of 2,4,6-trinitrophenol is 0.6, a very strong acid 24 Preparation of Alchols: an Overview • Alcohols are derived from many types of compounds • The alcohol hydroxyl can be converted to many other functional groups • This makes alcohols useful in synthesis 25 Review: Preparation of Alcohols by Regiospecific Hydration of Alkenes • Hydroboration/oxidation: syn, non-Markovnikov hydration • Oxymercuration/reduction: Markovnikov hydration 26 Preparation of 1,2-Diols • Review: Cis 1,2-diols from hydroxylation of an alkene with OsO4 followed by reduction with NaHSO3 • In Chapter 18: Trans-1,2-diols from acid-catalyzed hydrolysis of epoxides 27 Alcohols from Reduction of Carbonyl Compounds • Reduction of a carbonyl compound in general gives an alcohol • Note that organic reduction reactions add the equivalent of H2 to a molecule 28 Reduction of Aldehydes and Ketones • Aldehydes gives primary alcohols • Ketones gives secondary alcohols 29 Catalytic Hydrogenation: O RCH aldehyde + H2 Pt, Pd or Ni RCH2OH primary alcohol O Pt, Pd or Ni RCR' + H2 ketone OH RCHR' secondary alcohol 30 Reduction Reagent: Sodium Borohydride • NaBH4 is not sensitive to moisture and it does not reduce other common functional groups • Lithium aluminum hydride (LiAlH4) is more powerful, less specific, and very reactive with water • Both add the equivalent of “H-” 31 32 Mechanism of Reduction • The reagent adds the equivalent of hydride to the carbon of C=O and polarizes the group as well Not a complete mechanism!!! 33 Reduction of Carboxylic Acids and Esters • Carboxylic acids and esters are reduced to give primary alcohols • LiAlH4 is used because NaBH4 is not effective 34 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 35 36 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 37 Examples of Reactions of Grignard Reagents with Carbonyl Compounds • Formaldehyde reacts with Grignard reagents to yield primary alcohols. • Aldehydes react with Grignard reagents to yield secondary alcohols. • Ketones yield tertiary alcohols. 38 Examples of Reactions of Grignard Reagents with Carbonyl Compounds 39 Reactions of Esters and Grignard Reagents • Yields tertiary alcohols in which two of the substituents carbon come from the Grignard reagent • Grignard reagents do not add to carboxylic acids – they undergo an acid-base reaction, generating the hydrocarbon of the Grignard reagent 40 Grignard Reagents and Other Functional Groups in the Same Molecule • Can't be prepared if there are reactive functional groups in the same molecule, including proton donors 41 42 43 Synthesis of Diols Catalytic hydrogenation: O O HCCH2CHCH2CH OH H2 Ni, 125oC OH CH2CH2CHCH2CH2 CH3 CH3 3-Methylpentanedial 3-Methyl-1,5-pentanediol 44 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 45 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 46 Acid-Catalyzed Dehydration • Tertiary alcohols are readily dehydrated with acid • Secondary alcohols require severe conditions (75% H2SO4, 100°C) - sensitive molecules don't survive • Primary alcohols require very harsh conditions – impractical • Reactivity is the result of the nature of the carbocation intermediate (See Figure 17-5) • Note that Zaitsev’s rule is followed! 47 48 Dehydration with POCl3 • Phosphorus oxychloride in the amine solvent pyridine can lead to dehydration of secondary and tertiary alcohols at low temperatures • An E2 via an intermediate ester of POCl2 (see Figure 17.6) N pyridine Follows an E2 mechanism 49 Mechanism 1: Dehydration of Alcohol (2 or 3 ) N H O+ OH O + POCl2 + Cl– P Cl Cl Cl H OPOCl2 N + OPOCl2 + + HCl H N 50 Conversion of Alcohols into Alkyl Halides • 3° alcohols are converted by HCl or HBr at low temperature (Figure 17.7) • 1° and alcohols are resistant to acid – use SOCl2 or PBr3 by an SN2 mechanism (ether solvent) 51 Mechanism 2: 52 Conversion of Alcohols into Tosylates • Reaction with p-toluenesulfonyl chloride (tosyl chloride, p-TosCl) in pyridine yields alkyl tosylates, ROTos • Formation of the tosylate does not involve the C–O bond so configuration at a chirality center is maintained • Alkyl tosylates react like alkyl halides 53 Stereochemical Uses of Tosylates • The SN2 reaction of an alcohol via a tosylate, produces inversion at the chiral center • The SN2 reaction of an alcohol via an alkyl halide proceeds with two inversions, giving product with same arrangement as starting alcohol 54 55 56 Oxidation of Alcohols • Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive reagents 57 58 Oxidation of Primary Alcohols • To aldehyde: pyridinium chlorochromate (PCC, C5H6NCrO3Cl) in dichloromethane – Other reagents produce carboxylic acids • Converts secondary alcohol to ketone 59 Oxidation of Primary Alcohols • Jones’ Reagent: CrO3 in aqueous sulfuric acid. – Oxidizes primary alcohols to carboxylic acids: All of the oxidations occur via an E2 mechanism. 60 Mechanism of Chromic Acid Oxidation • Alcohol forms a chromate ester followed by elimination with electron transfer to give ketone • The mechanism was determined by observing the effects of isotopes on rates 61 Oxidation of Secondary Alcohols • Na2Cr2O7 in aqueous acetic acid is an inexpensive oxidizing agent: CH3 OH Na2Cr2O7 acetic acid 4-tert-Methylcyclohexanol CH3 O 4-tert-Methylcyclohexanone 62 Example 5: Predict the major organic product OH Cl K2Cr2O7 acetic acid OH PCC CH2Cl2 63 Protection of Alcohols • Hydroxyl groups can easily transfer their proton to a basic reagent • This can prevent desired reactions • Converting the hydroxyl to a (removable) functional group without an acidic proton protects the alcohol 64 Methods to Protect Alcohols • Reaction with chlorotrimethylsilane in the presence of base yields an unreactive trimethylsilyl (TMS) ether • The ether can be cleaved with acid or with fluoride ion to regenerate the alcohol 65 66 Protection-Deprotection 67 Preparation and Uses of Phenols • Industrial process from readily available cumene • Forms cumene hydroperoxide with oxygen at high temperature 68 Laboratory Preparation of Phenols • From aromatic sulfonic acids by melting with NaOH at high temperature • Limited to the preparation of alkyl-substituted phenols 69 Reactions of Phenols • The hydroxyl group is a strongly activating, making phenols substrates for electrophilic halogenation, nitration, sulfonation, and Friedel–Crafts reactions • Reaction of a phenol with strong oxidizing agents yields a quinone • Fremy's salt [(KSO3)2NO] works under mild conditions through a radical mechanism 70 71