《有机化学》课程教学课件（Organic Chemistry, Alex Jonathan Roche lecture notes Rutgers The State University NJ, wade 8th）Chapter 11 Reactions of Alcohols

Reactions of Alcohols Alcohols are versatile organic compounds since they undergo a wide variety of transformations-the majority of which are either oxidation or reduction type reactions. Normally:Oxidation is a loss of electrons;Reduction is a gain of electrons. OXIDATION But in organic terms: OH Io] H →R CH[OL,R- Oxidation H H +H0 loss of H2; alkane primary alcohol aldehyde carboxylie acid addition of O or O2; no bonds to O one bond to O two bonds to O three honds to O addition of X2 (halogens). H OH Reduction: R'10L,R-C-R1OL,R-C-R'(no further oxidation) addition of H2 or H; H +B0 loss of O or O2 alkane secondary alcohol ketone loss of X2. no bonds to o one bond to O two bonds to 0 OH (Neither an oxidation or 101,R-C- -R'(usually no further oxidation) reduction: Addition or loss of H, R" H2O.,HX). alkane tertiary alcohol no bonds to one bond to O REDUCTION ChlI Reacns of Alcohols (landscape) Page I

Ch11 Reacns of Alcohols (landscape) Page 1 Reactions of Alcohols Alcohols are versatile organic compounds since they undergo a wide variety of transformations – the majority of which are either oxidation or reduction type reactions. Normally: Oxidation is a loss of electrons; Reduction is a gain of electrons. But in organic terms: Oxidation: loss of H2; addition of O or O2; addition of X2 (halogens). Reduction: addition of H2 or H- ; loss of O or O2; loss of X2. (Neither an oxidation or reduction: Addition or loss of H+ , H2O, HX)

Oxidation of Alcohols Primary and secondary alcohols are easily oxidized by a variety of reagents Secondary Alcohols The most common reagent used for oxidation of secondary alcohols to ketones is chromic acid,H2CrO4. OH Na,Cr2O-/H2SO4 RCHR R C-R secondary alcohol ketone Example H NaCr207 OH H2SO4 cyclohexanol cyclohexanone (90%) 中1 Chromic acid is produced in situ by reaction of sodium dichromate,sulfuric acid and water. Na,Cr2O7+H2O+2H2SO>2 H2CrO+2 NaHSO Ch!I Reacns of Alcohols (landscape) Page 2

Ch11 Reacns of Alcohols (landscape) Page 2 Oxidation of Alcohols Primary and secondary alcohols are easily oxidized by a variety of reagents. Secondary Alcohols The most common reagent used for oxidation of secondary alcohols to ketones is chromic acid, H2CrO4. Chromic acid is produced in situ by reaction of sodium dichromate, sulfuric acid and water. Na2Cr2O7 + H2O + 2H2SO4  2 H2CrO4 + 2 NaHSO4

Mechanism of oxidation R一C-O-H+H-O 0H→ RC—O— OH H,O H alcohol chromic acid chromate ester The alcohol and chromic acid produce a chromate ester,which then reductively eliminates the Cr species. The Cr is reduced (VI->IV),the alcohol is oxidized. R R R- Cr-OH R-C=0: Ci-OH H,O:H .0.4 HO+ 0 Cr(VI) Cr(IV) Oxidation of Primary Alcohols Primary alcohols are easily oxidized just like secondary alcohols,but the product of oxidation is an aldehyde RY十HOLRH回 OH 0 0 R--OH primary aldehyde acid alcohol However,the aldehyde can also be easily oxidized to an acid,and this 'over-oxidation'is a practical problem. ChlI Reacns of Alcohols (landscape) Page 3

Ch11 Reacns of Alcohols (landscape) Page 3 Mechanism of oxidation The alcohol and chromic acid produce a chromate ester, which then reductively eliminates the Cr species. The Cr is reduced (VI IV), the alcohol is oxidized. Oxidation of Primary Alcohols Primary alcohols are easily oxidized just like secondary alcohols, but the product of oxidation is an aldehyde. However, the aldehyde can also be easily oxidized to an acid, and this ‘over-oxidation’ is a practical problem. R OH H H R O H R O OH primary alcohol aldehyde acid [O] [O]

E.g CH2OH Na2Cr2O7,H2SO4 CO2H A common reagent that selectively oxidizes a primary alcohol to an aldehyde (and no further)is pyridinium chlorochromate,PCC. N: CrO3.HCI (PCC) E.g. 入OH_PCC入 aldehyde Tertiary Alcohols These are resistant to oxidation because they have no hydrogen atoms attached to the oxygen bearing carbon (carbinol carbon). ChlI Reacns of Alcohols (landscape) Page 4

Ch11 Reacns of Alcohols (landscape) Page 4 E.g. A common reagent that selectively oxidizes a primary alcohol to an aldehyde (and no further) is pyridinium chlorochromate, PCC. E.g. Tertiary Alcohols These are resistant to oxidation because they have no hydrogen atoms attached to the oxygen bearing carbon (carbinol carbon). N: CrO3 , HCl (PCC) OH PCC O H aldehyde

Other Oxidizing Reagents Potassium permanganate is a cheaper but stronger oxidizing agent,and conditions must be controlled carefully. OH 人OH KMnO4.base 入、0 Thermal dehydrogenation is the cheapest method of oxidation but the high temperatures involved limit the applicability of this method. H OHCu0,300°C Reduction of Alcohols Normally an alcohol cannot be directly reduced to an alkane in one step. LiAHA The-OH group is a poor leaving group so hydride displacement is not a good option-however the hydroxyl group is easily converted into other groups that are superior leaving groups,and allow reactions to proceed. ChlI Reacns of Alcohols (landscape) Page 5

Ch11 Reacns of Alcohols (landscape) Page 5 Other Oxidizing Reagents Potassium permanganate is a cheaper but stronger oxidizing agent, and conditions must be controlled carefully. Thermal dehydrogenation is the cheapest method of oxidation but the high temperatures involved limit the applicability of this method. Reduction of Alcohols Normally an alcohol cannot be directly reduced to an alkane in one step. The –OH group is a poor leaving group so hydride displacement is not a good option – however the hydroxyl group is easily converted into other groups that are superior leaving groups, and allow reactions to proceed. OH KMnO4 , base O OH H OH O CuO, 300 oC H OH LiAlH4 X H H

One such conversion involves tosyl chloride,and the formation of a tosylate (These compounds undergo substitution and elimination very easily,often more reactive than alkyl halides). OH TsCl Nuc: ·-OTs pyridine (substitution) or elimination: B一H+OTs (elimination) B: Cyclohexanol will not reduce with LiAlH,but the corresponding tosylate reduces to cyclohexane very easily. H OH Ts-CI,py 0- CHs LiAH Ts or Tosyl- cyclohexyl tosylate ChlI Reacns of Alcohols (landscape) Page 6

Ch11 Reacns of Alcohols (landscape) Page 6 One such conversion involves tosyl chloride, and the formation of a tosylate. (These compounds undergo substitution and elimination very easily, often more reactive than alkyl halides). Cyclohexanol will not reduce with LiAlH4, but the corresponding tosylate reduces to cyclohexane very easily. H OH H O S O O CH3 Ts or Tosyl￾Ts-Cl, py cyclohexyl tosylate H H LiAlH4

Tosylate Esters C R-0: -0- CH3 pyridine p-toluenesulfonyl chloride ROTs,a tosylate ester TsCI,"tosyl chloride" Tosylate esters(tosylates)are typically formed from alcohols with reaction with Ts-Cl and pyridine(py). Tosylate groups undergo a variety of S2 reactions. CHCH2 S2 CH2CH3 C -Ts I一C H H +:0Ts iodide CH CH tosylate ion (S)-2-butyl tosylate (R)-2-butyl iodide The tosylate is such a good leaving group because it is a stable anion. ChlI Reacns of Alcohols (landscape) Page 7

Ch11 Reacns of Alcohols (landscape) Page 7 Tosylate Esters Tosylate esters (tosylates) are typically formed from alcohols with reaction with Ts-Cl and pyridine (py). Tosylate groups undergo a variety of SN2 reactions. The tosylate is such a good leaving group because it is a stable anion

The tosylate is such a good leaving group because it is a stable anion -OTs CH. CH← tosylate ion resonance-stabilizedanion 3 Pewon Edicon inc Common SN2 transformations of Tosylates: R-OTs O-H R-OH "C≡N R-CN Br R-Br R-O R-OR' :NHg R-NH2 LiAH4 R-H Ch!I Reacns of Alcohols (landscape) Page 8

Ch11 Reacns of Alcohols (landscape) Page 8 The tosylate is such a good leaving group because it is a stable anion. Common SN2 transformations of Tosylates: R OTs -O H - C N R' O - Br - :NH3 LiAlH4 R-OH R-CN R-Br R-OR' R-NH2 R-H

Alcohols and Hydrohaloic Acids Alkyl halides can also be formed by reaction of alcohols with H-X acids. R-OH+H-Br→R-Br+H2O In acidic media,the alcohol is in equilibrium with its protonated form. H R-9-H X H+ R十O-H SNI or SN2 R一X poor leaving group good leaving group 2013 Puarson Educalcn.ie The-OH is a poor leaving group,but-OH2 is an excellent leaving group,and once the-OH is protonated the molecule may take place in a variety of substitution and/or elimination reactions. The nature of R determines whether the reactions proceed via SNI or SN2 mechanisms (If R is primary alkylSN2 If R is bulky tertiary alkyl->SN1). ChlI Reacns of Alcohols (landscape) Page 9

Ch11 Reacns of Alcohols (landscape) Page 9 Alcohols and Hydrohaloic Acids Alkyl halides can also be formed by reaction of alcohols with H-X acids. R-OH + H-Br  R-Br + H2O In acidic media, the alcohol is in equilibrium with its protonated form. The –OH is a poor leaving group, but –OH2 + is an excellent leaving group, and once the -OH is protonated the molecule may take place in a variety of substitution and/or elimination reactions. The nature of R determines whether the reactions proceed via SN1 or SN2 mechanisms. (If R is primary alkyl  SN2 If R is bulky tertiary alkyl  SN1)

SN2: CH:CH2CH2 CH3CH2CH2 CH2CHCH3 HC--H二 H 1 Br一CH +H2O :Br:H H butan-1-ol 1-bromobutane SNI: CH3 CH3 CH3 H3C- C-0-H H3C一 :Br CH3 CH3 CH3 CH3 H3C- Br: CH3 ChlI Reacns of Alcohols (landscape) Page 10

Ch11 Reacns of Alcohols (landscape) Page 10 SN2: SN1: