8Chapter 15

8Chapter 15 - Chapter 15 Alcohols, Diols, and Thiols 15-1...

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Unformatted text preview: Chapter 15 Alcohols, Diols, and Thiols 15-1 15.1 Sources of Alcohols 15-2 Methanol Methanol Methanol is an industrial chemical end uses: solvent, antifreeze, fuel principal use: preparation of formaldehyde 15-3 Methanol Methanol Methanol is an industrial chemical end uses: solvent, antifreeze, fuel principal use: preparation of formaldehyde prepared by hydrogenation of carbon prepared monoxide monoxide CO + 2H2 → CH3OH CO + 2H2 → CH3OH 15-4 Ethanol Ethanol Ethanol is an industrial chemical Most ethanol comes from fermentation Synthetic ethanol is produced by hydration of ethylene Synthetic ethanol is denatured (made unfit for drinking) by adding methanol, benzene, pyridine, castor oil, gasoline, etc. 15-5 Other alcohols Other alcohols Isopropyl alcohol is prepared by hydration of Isopropyl propene. propene. All alcohols with four carbons or fewer are All readily available. readily Most alcohols with five or six carbons are Most readily available. readily 15-6 Sources of alcohols Sources of alcohols Reactions discussed in earlier chapters (Table 15.1) Hydration of alkenes Hydroboration-oxidation of alkenes Hydrolysis of alkyl halides Syntheses using Syntheses Grignard reagents Grignard organolithium reagents 15-7 Sources of alcohols Sources of alcohols New methods in Chapter 15 Reduction of aldehydes and ketones Reduction of carboxylic acids Reduction of esters Reaction of Grignard reagents with epoxides Diols by hydroxylation of alkenes 15-8 15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones 15-9 Reduction of Aldehydes Gives Primary Alcohols Reduction of Aldehydes Gives Primary Alcohols R R C H O H C OH H 15-10 Example: Catalytic Hydrogenation Example: Catalytic Hydrogenation O CH3O CH CH + H2 Pt, ethanol Pt, CH3O CH CH2OH (92%) 15-11 Reduction of Ketones Gives Secondary Alcohols Reduction of Ketones Gives Secondary Alcohols R R C R' O H C OH R' 15-12 Example: Catalytic Hydrogenation Example: Catalytic Hydrogenation H O + H2 OH Pt Pt ethanol (93-95%) (93-95%) 15-13 Retrosynthetic Analysis Retrosynthetic Analysis R H C R OH R C R' O C O H H H C H:– R OH H:– R' 15-14 Metal Hydride Reducing Agents Metal Hydride Reducing Agents H H + Na H – B H Li + Al H H H Sodium borohydride H – Lithium aluminum hydride act as hydride donors 15-15 Examples: Sodium Borohydride Examples: Sodium Borohydride Aldehyde O2N O O2N NaBH4 NaBH CH2OH CH methanol methanol (82%) Ketone O NaBH4 ethanol H OH (84%) 15-16 Lithium aluminum hydride Lithium aluminum hydride more reactive than sodium borohydride cannot use water, ethanol, methanol etc. as solvents diethyl ether is most commonly used solvent 15-17 Examples: Lithium Aluminum Hydride Examples: Lithium Aluminum Hydride Examples: Aldehyde O CH3(CH2)5CH 1. LiAlH4 diethyl ether 2. H2O CH3(CH2)5CH2OH (86%) Ketone O (C6H5)2CHCCH3 1. LiAlH4 diethyl ether 2. H2O OH (C6H5)2CHCHCH3 (84%) 15-18 Selectivity Selectivity neither NaBH4 or LiAlH4 reduces isolated double bonds O 1. LiAlH4 diethyl ether 2. H2O (90%) H OH 15-19 15.3 Preparation of Alcohols By Reduction of Carboxylic Acids and Esters 15-20 Reduction of Carboxylic Acids Reduction of Carboxylic Acids Gives Primary Alcohols Gives Primary Alcohols R R C HO O H C OH H llithium aluminum hydride is only ithium effective reducing agent effective 15-21 Example: Reduction of a Carboxylic Acid Example: Reduction of a Carboxylic Acid O 1. LiAlH4 diethyl ether COH COH 2. H2O CH2OH CH (78%) 15-22 Reduction of Esters Reduction of Esters Gives Primary Alcohols Gives Primary Alcohols (Also Chapter 19) (Also Chapter 19) Lithium aluminum hydride preferred for laboratory reductions Sodium borohydride reduction is too slow to be useful Catalytic hydrogenolysis used in industry but conditions difficult or dangerous to duplicate but in the laboratory (special catalyst, high in temperature, high pressure 15-23 Example: Reduction of an Ester Example: Reduction of an Ester O COCH2CH3 1. LiAlH4 diethyl ether 2. H2O CH2OH + CH CH3CH2OH (90%) 15-24 15.4 Preparation of Alcohols From Epoxides 15-25 Reaction of Grignard Reagents Reaction of Grignard Reagents with Epoxides with Epoxides R MgX CH2 H2C O R CH2 CH CH2 OMgX H3O+ RCH2CH2OH 15-26 Example Example Example CH2 CH3(CH2)4CH2MgBr + H2C O 1. diethyl ether 2. H3O+ CH3(CH2)4CH2CH2CH2OH (71%) 15-27 15.5 Preparation of Diols 15-28 Diols are prepared by... Diols are prepared by... reactions used to prepare alcohols hydroxylation of alkenes 15-29 Example: reduction of a dialdehyde Example: reduction of a dialdehyde O O HCCH2CHCH2CH CH CH3 CH H2 (100 atm) Ni, 125°C HOCH2CH2CHCH2CH2OH CH3 3-Methyl-1,5-pentanediol (81-83%) 15-30 Hydroxylation of Alkenes Hydroxylation of Alkenes Gives Vicinal Diols Gives Vicinal Diols vicinal diols have hydroxyl groups on adjacent vicinal carbons carbons ethylene glycol (HOCH2CH2OH) is most familiar OH) example example 15-31 Osmium Tetraoxide is Key Reagent Osmium Tetraoxide is Key Reagent syn addition of —OH groups to each carbon of double bond C C C HO C C OH C O O Os O O 15-32 Example Example Example CH3(CH2)7CH CH2 (CH3)3COOH OsO4 (cat) tert-Butyl alcohol HO– CH3(CH2)7CHCH2OH OH (73%) (73%) 15-33 Example Example Example H (CH3)3COOH OsO4 (cat) H tert-Butyl alcohol HO– H H HO OH (62%) (62%) 15-34 15.6 Reactions of Alcohols: A Review and a Preview 15-35 Table 15.2 Review of Reactions of Alcohols Table 15.2 Review of Reactions of Alcohols reaction with hydrogen halides reaction reaction with thionyl chloride reaction reaction with phosphorous reaction tribromide tribromide acid-catalyzed dehydration conversion to p-toluenesulfonate conversion -toluenesulfonate esters esters 15-36 New Reactions of Alcohols in This New Reactions of Alcohols in This New New Chapter Chapter Chapter Chapter conversion to ethers esterification esters of inorganic acids oxidation cleavage of vicinal diols 15-37 15.7 Conversion of Alcohols to Ethers 15-38 Conversion of Alcohols to Ethers Conversion of Alcohols to Ethers RCH2O CH2R H OH H+ RCH2O CH2R + H OH acid-catalyzed referred to as a "condensation" equilibrium; most favorable for primary alcohols 15-39 Example Example 2CH3CH2CH2CH2OH H2SO4, 130°C CH3CH2CH2CH2OCH2CH2CH2CH3 (60%) 15-40 Mechanism of Formation of Diethyl Ether Mechanism of Formation of Diethyl Ether Mechanism Mechanism Step 1: •• CH3CH2O • • + CH3CH2O • CH • H H H + H OSO2OH – OSO2OH 15-41 Mechanism of Formation of Diethyl Ether Mechanism of Formation of Diethyl Ether Mechanism Mechanism Step 2: H CH3CH2 O • + • •• CH3CH2O • • H CH3CH2 + CH3CH2O • • H + • O• •• H H H 15-42 Mechanism of Formation of Diethyl Ether Mechanism of Formation of Diethyl Ether Mechanism Mechanism Step 3: CH3CH2 CH3CH2 + CH3CH2O • • + CH3CH2O • H •• • •• • OSO2OH –• •• H •• OSO2OH •• 15-43 Intramolecular Analog Intramolecular Analog HOCH2CH2CH2CH2CH2OH H2SO4 130° O (76%) reaction normally works reaction well well only for 5- and 6membered rings 15-44 Intramolecular Analog Intramolecular Analog HOCH2CH2CH2CH2CH2OH via: H2SO4 130° •• •• O •O • H H O• + • H (76%) 15-45 15.8 Esterification (more on esters and other acid derivatives in later chapters) 15-46 Esterification Esterification O ROH + O H + R'COH R'COR + H2O a condensation reaction called Fischer esterification acid catalyzed reversible 15-47 Example of Fischer Esterification Example of Fischer Esterification O COH + CH3OH 0.1 mol 0.6 mol (i.e. excess) H2SO4 O COCH3 + COCH H2O 70% yield based on benzoic acid 15-48 Reaction of Alcohols with Acyl Chlorides Reaction of Alcohols with Acyl Chlorides O ROH + R'CCl O R'COR + HCl high yields not reversible when carried out in presence of pyridine 15-49 Example Example Example CH3CH2 O OH + O2N CCl CH3 pyridine CH3CH2 O NO2 OC CH3 (63%) (63%) 15-50 Reaction of Alcohols with Acid Anhydrides Reaction of Alcohols with Acid Anhydrides OO ROH + R'COCR' O R'COR + O R'COH analogous to reaction with acyl analogous chlorides chlorides 15-51 Example Example OO C6H5CH2CH2OH + F3CCOCCF3 pyridine O C6H5CH2CH2OCCF3 (83%) 15-52 Esters of Inorganic Acids 15-53 Esters of Inorganic Acids Esters of Inorganic Acids ROH + HOEWG ROEWG + H2O EWG is an electron-withdrawing group + HONO2 (HO)2SO2 (HO)3P – O 15-54 Esters of Inorganic Acids Esters of Inorganic Acids ROH + HOEWG ROEWG + H2O EWG is an electron-withdrawing group + HONO2 (HO)2SO2 (HO)3P CH3OH + HONO2 – O CH3ONO2 + H2O (66-80%) 15-55 15.9 Oxidation of Alcohols 15-56 Oxidation of Alcohols Oxidation of Alcohols Primary alcohols RCH2OH O O RCH RCOH Secondary alcohols OH O RCHR' from H2O RCR' 15-57 Typical Oxidizing Agents Typical Oxidizing Agents Aqueous solution Mn(VII) Mn(VII) Cr(VI) Cr(VI) KMnO4 KMnO H2CrO4 H2Cr2O7 15-58 Aqueous Cr(VI) Aqueous Cr(VI) FCH2CH2CH2CH2OH K2Cr2O7 H2SO4 H2O O FCH2CH2CH2COH (74%) 15-59 Aqueous Cr(VI) Aqueous Cr(VI) H FCH2CH2CH2CH2OH K2Cr2O7 OH H2SO4 H2O Na2Cr2O7 H2SO4 H2O O FCH2CH2CH2COH (74%) O (85%) 15-60 Nonaqueous Sources of Cr(VI) Nonaqueous Sources of Cr(VI) All are used in CH2Cl2 Pyridinium dichromate (PDC) (C5H5NH+)2 Cr2O72– Cr Pyridinium chlorochromate (PCC) C5H5NH+ ClCrO3– 15-61 Example: Oxidation of Example: Oxidation of Example: Example: a primary alcohol with PCC a primary alcohol with PCC PCC PCC (pyridinium chlorochromate) + N (pyridinium chlorochromate) ClCrO3– H CH3(CH2)5CH2OH PCC CH2Cl2 O CH3(CH2)5CH (78%) 15-62 Example: Oxidation of Example: Oxidation of Example: Example: a primary alcohol with PDC a primary alcohol with PDC PDC PDC (pryidinium dichromate) (pryidinium dichromate) (CH3)3C CH2OH CH PDC CH2Cl2 O (CH3)3C CH CH (94%) 15-63 Mechanism Mechanism H C O HOCrOH OH O iinvolves formation nvolves and elimination of a chromate ester chromate H O C O CrOH O 15-64 H Mechanism Mechanism H C O H •• O HOCrOH OH •• O H O C O CrOH O iinvolves formation nvolves and elimination of a chromate ester chromate C O 15-65 15.10 Biological Oxidation of Alcohols 15-66 Enzyme-catalyzed Enzyme-catalyzed CH3CH2OH + + NAD (a coenzyme) alcohol alcohol dehydrogenase dehydrogenase CH3CH O + NAD H + H+ 15-67 Figure 15.3 Structure of NAD++ Figure 15.3 Structure of NAD _ O OO O O HO HO HO P O O P _ O N N HO H O OH N + C NH2 O NH2 nicotinamide adenine dinucleotide (oxidized nicotinamide form) form) 15-68 Enzyme-catalyzed Enzyme-catalyzed H O CNH2 CH3CH2OH + + N + H+ R 15-69 Enzyme-catalyzed Enzyme-catalyzed Enzyme-catalyzed O CH3CH H H O CNH2 •• N R 15-70 15.11 Oxidative Cleavage of Vicinal Diols 15-71 Cleavage of Vicinal Diols by Periodic Acid Cleavage of Vicinal Diols by Periodic Acid C HO HIO4 C C O+O C OH 15-72 Cleavage of Vicinal Diols by Periodic Acid Cleavage of Vicinal Diols by Periodic Acid CH3 CH CH HO CCH3 OH HIO4 O CH CH O + CH3CCH3 (83%) 15-73 Cyclic Diols are Cleaved Cyclic Diols are Cleaved OH OH HIO4 O O HCCH2CH2CH2CH OH 15-74 15.12 Preparation of Thiols 15-75 Nomenclature of Thiols Nomenclature of Thiols 1) analogous to alcohols, but suffix is -thiol thiol rather than -ol rather 2) final -e of alkane name is retained, not 2) final dropped as with alcohols dropped 15-76 Nomenclature of Thiols Nomenclature of Thiols 1) analogous to alcohols, but suffix is -thiol thiol rather than -ol rather 2) final -e of alkane name is retained, not 2) final dropped as with alcohols dropped CH3CHCH2CH2SH CH3 3-Methyl-1-butanethiol 15-77 Properties of Thiols Properties of Thiols 1. low molecular weight thiols have foul odors 2. hydrogen bonding is much weaker in thiols 2. than in alcohols in 3. thiols are stronger acids than alcohols 4. thiols are more easily oxidized than 4. alcohols; oxidation takes place at sulfur oxidation 15-82 Thiols are less polar than alcohols Thiols Methanol Methanethiol bp: 65°C bp: 6°C Thiols are stronger acids than alcohols Thiols are stronger acids than alcohols have pKas of about 10; can be of deprotonated in aqueous base aqueous •• RS •• – •• H + • OH stronger acid (pKa = 10) • •• •• – RS • •• • +H •• OH •• weaker acid (pKa = 15.7) 15-83 RS– and HS – are weakly basic and good nucleophiles RS C6H5S H H Cl C6H5SNa (75%) SN2 KSH Br Br SN2 SH SH (67%) Oxidation of thiols take place at sulfur Oxidation of thiols take place at sulfur •• RS •• H thiol (reduced) •• RS •• •• SR •• disulfide (oxidized) thiol-disulfide redox pair is important in thiol-disulfide biochemistry biochemistry other oxidative processes place 1, 2, or 3 other oxygen atoms on sulfur oxygen 15-84 Oxidation of thiols take place at sulfur Oxidation of thiols take place at sulfur •• RS •• H •• RS •• •• SR •• thiol disulfide •• •• – •O • • •+ RS •• OH sulfenic acid RS •• OH sulfinic acid •• – •O • • • 2+ RS OH •O • •• – •• sulfonic acid 15-85 Example: sulfide-disulfide redox pair Example: sulfide-disulfide redox pair SH O HSCH2CH2CH(CH2)4COH O2, FeCl3 S S O (CH2)4COH α-Lipoic acid (78%) 15-86 15.13 Spectroscopic Analysis of Alcohols 15-87 Infrared Spectroscopy Infrared Spectroscopy Infrared –1 O—H stretching: 3200-3650 cm–1 (broad) –1 C—O stretching: 1025-1200 cm–1 (broad) C—O 15-88 Figure 15.4: Infrared Spectrum of Cyclohexanol Figure 15.4: Infrared Spectrum of Cyclohexanol OH OH C—H O—H C—O 3500 3000 2500 2000 1500 1000 500 Wave number, cm-1 15-89 H NMR H NMR 11 chemical shift of O—H proton is variable; chemical depends on temperature and concentration depends O—H proton can be identified by adding D2O; O; signal for O—H disappears (converted to O—D) signal H δ 3.3-4 ppm 3.3-4 C O H δ 0.5-5 ppm 0.5-5 15-90 Figure 15.5 (page 607) CH2CH2OH 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 Chemical shift (δ, ppm) 15-91 C NMR C NMR 13 13 chemical shift of C—OH is δ 60-75 ppm chemical —OH C—O is about 35-50 ppm less shielded than C —O —H CH3CH2CH2CH3 δ 13 ppm 13 CH3CH2CH2CH2OH δ 61.4 ppm 61.4 15-92 UV-VIS UV-VIS Unless there are other chromophores in the molecule, alcohols are transparent above about 200 nm; about λmax for methanol, for example, is 177 nm. 15-93 Mass Spectrometry of Alcohols Mass Spectrometry of Alcohols molecular ion peak is usually molecular small small a peak corresponding to loss of peak H2O from the molecular ion (M - 18) from is is usually present peak corresponding to loss of an alkyl group to give an oxygenstabilized carbocation is usually 15-94 Mass Spectrometry of Alcohols Mass Spectrometry of Alcohols molecular ion peak is usually molecular small small a peak corresponding to loss of peak H2O from the molecular ion (M - 18) from is is usually present R R peak corresponding to loss of an R • alkyl group to give an oxygenstabilized carbocation is usually CH2 •• OH •• •+ CH2 OH CH2 + OH •• •• 15-95 End of Chapter 15 ...
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