Chapter 17 Alcohols and Phenols Naming of Alkyl Alcohols

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					 Chapter 17: Alcohols and Phenols
 Naming of Alkyl Alcohols:
              H                             H                            R

      H                OH           R                OH          R               OH

              R                             R                            R
          Primary                       Secondary                    Tertiary
          Alcohol                       Alcohol                      Alcohol
Compounds that have the alcohol functional group as the highest priority group end with the suffix -ol.
IUPAC Rules for Naming Alcohols:
      1. Find the root name by selecting the alkyl chain that posses the hydroxyl functional group and adding
      the -ol suffix on the end instead of the -e.
      2. Number the alkane chain beginning at the end nearer the hydroxyl group.
      3. Number the substituents according to chain position and list names in alphabetical order.
                                                          HO

                  OH        Br
                                                                                                 OH                             OH



          1-Bromo-3-pentanol            3-Ethyl-7,7-dimethyl-2-octanol       trans-4-Methyl-cyclohexanol           2-Methyl-2-propanol
                                                                                                                           or
                                                                                                                      tert-butanol

  Naming of Phenols (Aromatic Alcohols):
  Phenols only refer to compounds with hydroxyl groups driectly on the phenyl ring. These compounds are
  named in the same manner as substituted benzenes with the exception that the word benzene in the name is
  switched with the word phenol.
  Special Properties of Alcohols:
  Boiling points of alkyl alcohols are elevated
  relative to the correspodning alkane or alkanes
                                                                                         δ    Oδ                     δ     Oδ
  with similar molecular weights. This property                              δ
                                                                                         H                           H
  is a result of the hydrogen bonding observed in                            H                       H
                                                                                     O               δ     O
  hydroxylated compounds. Phenols also                                           δ                             δ
  experience the same property relative to non-
  hyroxy aromatic compounds.
                                                                             Representative Hydrogen Bonding in Ethanol

Alcohols can be both weakly acidic and weakly basic.
                                                     H
                                                                                                           Base
  R       O             H                                                            R       O                                  R        O
                                        R        O
                    (Strong Acid)                                                                                            Alkoxide Anion
              H                                      H                                           H
Alcohol acting                          Oxonium Ion                              Alcohol acting
  as a Base                                                                       as an Acid
 Electron witdrawing groups on the alcohol increase acidity and electron donating groups decrease acidity.
 In general phenols are more acidic then alkyl alcohols. Alcohols are acidic enough to react with baes such as
 NaH, NaNH2, Grinard reagents (MgXR), and Lithium Reagents. Alkoxides are generally strong bases.
Preparations of Alcohols
   Acid catalyzed addition of water to an alkene:

                                                                                           HO     H                        OH
                                  H                                            H2O                           -H



                                              note: intermediate carbocation can lead to undesireable reactions
   Oxymercuration of alkenes:
                                                                                                             HO            H
                      AcO             OAc
                              Hg                                 Hg        OAc       H2O


                                                                                                                      Hg        OAc
             OH                                                                       OH

                                      NaBH4
                                  (hydride source)
                 Hg         OAc


   Hydroboration (no mechanism), always produces anti Markovnikov product, with syn regioselectivity:

                                                               OH               Added H and OH are syn

                  CH3
                              (1) BH3, THF
                                                                      H
                              (2) H2O2, - OH

                                                                      CH3

           peracid                      O                                 OH
         (R-COOOH)                              H3O
                                                                                 hydroxyl groups add anti to one another

                                                                          OH

                                                          OH
                        OsO4
                                                                    hydroxyl groups add syn to one another
                       NaHSO4
          KMNO4 gives same reaction                       OH

Reduction of Carbonyl Compounds to Generate Alcohols

         O                                    OH                                 O                                    OH
                       reducing                                                             reducing
     R       H           agent          R          H                                          agent
                                                                            R        R'                           R        R'
     aldehyde                               primary                            ketone                             secondary
                                            alcohol                                                               alcohol
 Common Reducing Agents Both of these reagents function by providing a hydride nucleophile H

 NaBH4 - Sodium Borohydride - can reduce both aldehydes and ketones, reduces esters very slowly won't
 reduce carboxylic acids at all, overall more mild.

 LiAlH4 - Lithium Aluminum Hydride- can reduce aldehydes, ketones, esters, and acids, more dangerous.

 Examples:
                                                                       O                                       OH
     O           NaBH4         OH                                                LiAlH4

                                                                       OH


                                                                       O                                       OH
             O                             OH
                      LiAlH4                             O                        LiAlH4
                                                                            O
             OH                                                                                           + 2 Methanol
                                                             O                                       OH

Reaction of Grignard Reagents with Aldehydes and Ketones
   Grignard Formation
                                           O

                           δ   δ                             O                            OH
                 Mg                   R1       R2                     H3O
R    X                     R   MgX
         diethyl ether                                  R1       R2                R1          R2
                                                             R                            R
            or THF

 X=Cl, Br, or I
 R=primary, secondary, tertiary, aryl, or vinylic

Reaction of Grignard Reagents with Aldehydes and Ketones

         O                     δ     δ              O                               O                               OH
                               R     MgX                         R    MgX                           H3O
                      R2                                                    R1                R           R1              R
R1               O                             R1        R
                                                                                    R                               R
                                                                                                               Tertiary
                                                                                                               Alcohol
                                                                                                               Formed

Grignard Reagents will react with acidic protons to form an alkane. -OH, -NH, -SH, -COOH are acidic enough
to destroy the Grignard. Grignards also can not be made from alkyl halides that also contain carbonyls, since
the formed Grignard will react with iteslf. Fortunately, this problem can be overcome by protecting these
sensitive groups when using Grignards
Reactions of Alcohols
Dehydration-the loss of H2O from an alcohol to yield the alkene, acid catalyzed, follows the Zaitsev Rule, that
is this reaction gives the more stable substituted product, only preparatively useful with tertiary alcohols.
                                                                                H
                                                      OH2                                                       H
             OH         H2SO4                                - H2O


Dehydration with phosphorus oxychloride (POCl3):

             OH                                       POCl3 essentially converts -OH into a good leaving group and
                        POCl3
                                                      then procedes through an E2 mechansim.
                        pyridine


 Pinacol Rearrangement: acid catalyzed reaction with vicinal diols
                                                                           R2        R3                         R2
        R2   R3                             R2   R3                                               R1
                          H
R1                 R4              R1                  R4             R1                                              R3
        OH OH                               OH OH2
                                                                           OH        R4           HO            R4
     R1           R2
                                                 R1         R2                               R2
                                                                                    R1
                         R3
                                                                 R3                                    R3
  HO              R4                    H        O          R4                      O        R4
Groups migrate according to Migratory Aptitude: phenyl, alkyl, hydrogen
Coversion of an alcohol to an alkyl halide:
  tertiary alcohols: use HX, dehydration SN1 mechanism with halogen nuclophile
  primary and secondary: use SOCl2 or PBr3 , both occur by an SN2 mechansim with inversion of stereochem

Tosylation of Alcohols:                                                    OH                               O
                                                                                 TosCl                  O S
     Tosyl chloride in pyridine makes the tosyl ester
     Tosylation doesn't invert stereochemsitry                                  pyridine                    O



Oxidation of Alcohols: An alcohol can be oxidized to yeild a carbonyl compound.
Primary alcohols can be oxidized to an aldehyde or further to a carboxylic acid. Secondary alcohols can be
oxidized to ketones, tertiary alcohols cannot be oxidized.
   OH                                                                              Further
         Oxidation         O                                            O                       O
                                                HO         Oxidation               Oxidation
                                                                                         H                           OH

 Common Oxidizing Agents:
 KMnO4
 CrO3     typical oxidants- will oxidize primary alcohols to carboxylic acids and secondary alcohols to ketones
 Na2Cr2O7

 PCC (Pyridine CrO3Cl)-generally used for oxidizing primary alcohols to aldehydes.
Alcohol Protection: Protection is often needed in syntesis, for example when carrying out the Grignard
Reaction. The protecting group is attached to the substrate the reaction is carried out and then the protecting
group is removed.
                                                         Trimethylsilyl chloride protection of alcohols
Dihydropyaran protection of alcohols

                                                                                  Si   Cl
R         OH                                                                                              Si
                       O          R                           R        OH
                       H              O     O
                                                                                Pyridine      R       O

      deprotection: AcOH, THF, H2O
                                                                        deprotection: H , H2O, F
  Tert-butanol protection of alcohols

                           OH
 R        OH                      R
                       H              O


          deprotection: H , H2O
 Preparation of Phenols
 Oxidation of cumene to phenol
                                    OOH

                                                            OH
                  O2                        H3O                             O
                                                                   +

  cumene
Alkali fusion to produce phenol
               SO3H                                    OH
                                                            Note: the alkali fusion reaction requires harsh
                                                            solvent free conditions, therefore it is typically
                  NaOH, high heat
                                                            only useful with alkyl goups present on the ring
                       H3O
 Reactions of Phenols - Phenols are higly activated towards electrophilic aromatic stubstitution.

     OH                      O Na                            O
               NaOH                             CH3I
                                      H2O


                                                                                 O                             OH
     OH                      O
                                                                                       NaBH4 or SnCl2/ H2O
           (KSO3)2NO
                                                                                            Fremy's
                                                                                              Salt
                                                                                 O                             OH
                             O