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									             CHAPTER 12
               Substituted Benzene

12.1        Alkylbenzenes (Ar-R)
Bezylic carbons:

       CH3             CH2CH3        CH(CH3)2




1
    Reactions of Alkylbenzens
1. Free Radical Halogenation



         CH2CH3                Br
                  Br2          CHCH3
                   hv




2
                       R
2- Oxidation                KMnO4
                            hot
                                           CO2H




     CH3                   CO2H
           KMnO4
           hot

     CH2CH3    MnO4-                CO2H
                hot

      CH2CH3
      CHCH3    MnO4-                   CO2H
                hot

3
                              CH3
                                       MnO4-
Notice:                       CCH3
                              CH3       hot           No Reaction


                        Benzylic carbon has no hydrogen




          CH3
                MnO4-                          CO2H
    CH3         hot
                                HO2C




                                        CO2H
                MnO4-
                hot
                                         CO2H




4
                         Phenols (ArOH)
A phenol has a hydroxyl group directly attached
to the benzene ring
SP2- hybridized carbon




                OH



   C---O bond is not easily broken    No substitution or elimination reaction


      R-OH + HBr          RBr + H2O          SN1 or SN2


  5
      Ar-OH + HBr  No reaction
                    Acidity of Phenols
      CH3CH2OH        + NaOH         CH3CH2O- Na+        +   H2O    Not favored
      pKa= 16                                            pKa=15.7




               OH   + NaOH                 O- Na+    +    H2O       favored
                                                    pKa= 15.7
     pKa= 10


                               SN2
                O- + R X                            OR
                                                                +    X-

6   a phenoxide ion
    Esterfication of phenols
                O   O                   O
                                        OCCH3
      OH   + CH3C   OCCH3



                            + CH3CO2H




7
            The Kolbe Reaction
                  1) OH-                   OH
                  2) CO2
             OH
                  3) H+

                                           CO2H
Mechanism
                                                   O
    OH                      O-     + -
            OH-                  O C O             H
                                                  C O
                                                  O-


                           OH     H+
                                                    OH
                          CO2H
8    Salicylic acid                                 CO2-
    Importance of Kolbe Reaction
To Synthesize aspirin

                                            O
         OH            O O                 OCCH3
                +   CH3COCCH3
         CO2H                              CO2H

                                Acetylsalicylic acid

                                       (Aspirin)

9
      The Reimer-Tiemann Reaction
The reaction of phenol with chloroform in the
presence of base.


          OH                                      OH
                              OH- ,     
                1)   CHCl3,           70 C
                2)   H2O, H+
                                                   CH
                                                   O
                                        Salicylaldehyde
 10
Mechanism:
                               - H2O                Cl-
OH-                   H CCl3                 CCl3              CCl2
              +
                                                dichlorocarbene
                               H   ..
                                   CCl
                                                          CHCl2
          -                             2
      O            CCl2             O
              +
                                                          O-
                                                      OH-

                                                           H
              O                     O                     O
                  H       H+             H                CHCl

11
              OH                    O-                    O-
Oxidation of phenols: phenol resists
oxidation
Oxidation of hydroquinones (1,4-dimethoxy benzenes)
            OH                     O
                         O
                                            +   2   H+        +   2e
                                                                    -


                         H
            OH                     O

     hydroquinone
                                 1.4-benzoquinone
                                   (quinone)
                             O              O
                    OH
                                                +    2   H+       +     2e
                                                                          -


                    OH                      O
                             H
                                 1.2-benzoquinone
12
Preparation of Aniline

           HNO3                       NO2
           H2SO4

           Fe, HCl
                            N+H3Cl-    OH-   NH2
     NO2


                 H2, Pd/C or Pt




13
 Benzenediazonium Salts
                NaNO2, HCl, 0O C           +
                                           N N Cl-
        NH2                                           + H2O
                               benzenediazonium chloride

very reactive            Excellent leaving abilty of N2 gas


        +        _ N
        N N          2                      Nu -
                                    +                         Nu



 14
      Reactions of benzenediazinium Salts

                              Cl              Br
                                                                CN

                              CuCl
                                          CuBr
     1) HNO3, H2SO4
                                                          CuCN, KCN
     2) H2, Pt
               NaNO 2, HCl,           +
         NH2                          N N Cl-
                     O
                     0C
                                                           KI
                                                                      I
                H3PO2                     +         1)   HBF4
                                     H2O, H
                                               2)   heat
                                                                  F
                 H
                                        OH

15
Coupling reactions
             +
             N   N                 +
                                 N N


              +
            N N +           OH           N N      OH

      CO2H
                                       Azo compound
      NH2
                     O
     NaNO2, HCl, 0 C

     CO2H
         +                              N N      NHCH3
       N N +             NHCH3
16
Synthesis involving diazonium salts
                      ? ?     ?   ?
      CH3                               CH3            C N

      HNO3, H2SO4
                                                 CuCN, KCN



CH3          NO2
                                       CH3              N2+ Cl-
             1)   Fe, HCl
                          -
                     2) OH             NaNO2 ,
                                                 O
                                            HCl, O C
                          CH3         NH2

17
Nucleophilic Aromatic Substitution
                       Nu   -              No SN1 or SN2 reaction
            X     +



                                Nu   -               Nu
                   X    +                                 + X-
But


      Nucleophilic Aromatic Substitution




18
Examples

                             10%       NaOH
                 Cl                o                      OH
                             350 300 atm

increasing O2N          Cl     10% NaOH        O2N              OH
reactivity                               o
toward Nu -                            160
                                                P-nitrophenol
                  NO2                                  NO2
                                H2O
           O2N        Cl                      O2N         OH
                               warm
                  NO2                                  NO2

19
Other nucleophiles

            NO2
                                        NO2
                        NH3
     O2N         Cl              O 2N     NH2
                        heat



           NO2                          NO2
                      CH3CH2S-
O2N          Cl                  O2N      SCH2CH3
                       heat




20
Carbanion Mechanism:
If the ring is activated toward nucleophilc substitution by an
electron withdrawing group (I,e NO2)

Two steps 1) addition of Nu: to form carbanion
2) Loss of the halide ion
              OH-
                 slow                   OH
                          O2N                    fast   O2N   OH
O2N         Cl
                                        Cl
                                    -

                        Carbanion intermediate



21
Carbanion intermediate is stabilized by resonance

                                   O-            OH
                                        +
                                        N
                                   O-            Cl



          OH        O+      OH
 O2N                  N
         Cl        O-       Cl
                                   O+       OH
                                     N
                                  O-        Cl

22
Benzyne Mechanism:
If there is no electron withdrawing substituent on the
ring.                    -
                           NH2 , NH3
                      Cl                    NH2
Mechanism

         Cl
              - HCl
                                    NH2-         NH2
     H    NH2-
                      Benzyne              NH3


                             NH2-      +    NH2
23
     Benzyne

              H   H

          H

              H




24
Syntheses of substituted benzene compounds
                                    Cl
•    How would you synthesize

                                         NO2
                                                   Cl
                 HNO3                    Cl2
                 H2SO4            NO2
                                         FeCl3
                                                        NO2
•    But IF YOU START WITH CHLORINATION

                    Cl                   Cl        Cl
           Cl2                  HNO3                    NO2
                                H2SO4          +
           FeCl3
              o,p-director               NO2
25
Syntheses
                                          Br
                     ? ?   ?
                                               NH2
     HNO3
     H2SO4
                               1)   Fe, HCl
        NO2

        Br2, FeBr3                   2) OH-

                     Br

                               NO2
26
Note: Nitro group can be converted to arylamines which in turn can also
be converted to aryldiazonium salts,=> making a diversity of substituted
products

            1)   Fe, HCl           NaNO2, HCl            Nu
      NO2   2) OH-                     0o
                                                       N2+             Nu
                                 NH2
                                              easily displaced
m-director                 o,p-director

 Notice: Amino group does not undergo Friedel-Crafts reaction
 because an amino group reacts with Lewis acid since it is basic to
 form strongly deactivating grouo



                           +
                               AlCl3                          Al-Cl3
                  NH2                                         N+H2
                                             strongly deactivating
27
Nitrobenzene does not undergo Friedel-Crafts
reactions
                       O
                RX or RCX
         NO2                    No aromatic substitution
                    AlX3


Notice: An amino group is o,p-director, but an ammonium
group ( -NR3+) is an m-director and deactivating.


             NH2 + HNO3                       N+H3 NO3-


     o,p-director                      m-director

28
Sulfonic acid group (-SO3H)

The sulfonic acid group is easily removed and can be displaced by a
variety of reagents.


                          H2O, H+                      +    H2SO4
               SO3H



                            1)   Fused NaOH                      OH
               SO3H
                            2) H2O, H+

29
                              ? ?          ?
                                                         Br          OH
          Br2, FeBr3
                                                                H2O, H+
Br

          HNO3
          H2SO4

                       1)   Fe, HCl
Br            NO2                     Br       NH2 NaNO2,HCl   Br         N 2+
                       2)   OH-                     0o




     30
                                                              Br
                         ? ?       ?
                                                  Br
      HNO3
      H2SO4                                              CuBr


           NO2

     Br2, FeBr3
Br                            Br                         Br
               1)   Fe, HCl                  NaNO2,HCl
         NO2                           NH2                         N2+
               2) OH-                         0




31
                     ? ? ? ?             CO2H


                                         NH2
     CH3CH2Cl,
     AlCl3
                                         KMnO4
       CH2CH3                             heat



     HNO3, H2SO4
                   CH2CH3
                            1) Fe, HCl
                                   -       CH2CH3
                   NO2      2) OH


                                           NH2
32
                                      OCH3
               ? ? ? ?


                                    CH3I
     HNO3, H2SO4
                                       O-
       NO2


                                     NaOH
     H2,Pd/C
         NH2                          OH
                1)      NaNO2,HCl

                   2)   H2O, H+
33
                           Cl
               ? ?   ? ?

         CH3                     CO2H


     KMno4, heat

                                Cl2, FeCl3


          CO2H




34
                                               Cl
                       ? ? ? ?

                 CH3                                 CH3


            HNO3, H2SO4
                                                    H3PO2
      O2N


               CH3
            H2,Pd/C                                   Cl
                                         Cl-   N2+
     H2N
                       1)   Cl2, FeCl3
                 CH3 2) NaNO2, HCl                          CH3
35

								
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