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Carboxylic Acid Derivatives Nucl

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Carboxylic Acid Derivatives Nucl Powered By Docstoc
					         Chapter 19

Carboxylic Acid Derivatives:
Nucleophilic Acyl Substitution



                       WWU-Chemistry
               Assignment
• Skip the following sections:
  19.1, 19.11, 19.15, 19.16, 19.18,
  19.21 and 19.32

These PowerPoint slides have been revised
  for Fall 2007. Some additional sections
have been dropped or minimized!




                                      WWU-Chemistry
         Problem Assignment
• In-Text:
  1 a, c    4, 5a - d, 6 a - c     8 a, c
  9 -11     15 - 19      21 - 23   26, 27
      31 - 40
• End-of-Chapter:
  4         6-9          15


                                     WWU-Chemistry
The addition/elimination
      mechanism




                    WWU-Chemistry
Nucleophilic Acyl Substitution
 1)  Addition
                                  ..
         :O :                    :O :
                      slow
    R     C       Y          R    C     Y

              _                   Nu
    +    Nu:

 2) Elimination
          ..
        :O :                     :O :
                                                  _
    R     C       Y          R    C      +   Y:

          Nu                      Nu

                                        WWU-Chemistry
   Sect. 19.2, 19.3 and 19.4
Nomenclature for acid chlorides,
  acid anhydrides and esters

  Only ester nomenclature on test!




                            WWU-Chemistry
            O

     CH3 C        O      CH2 CH3

Acid part of ester Alcohol part of ester




                                  WWU-Chemistry
    O

CH3 C     O    CH2 CH3

Ethyl ethanoate (IUPAC)
Ethyl acetate (common)



                         WWU-Chemistry
              O

  CH3 CH      C     O       CH3

        CH3

Methyl 2-methylpropanoate



                             WWU-Chemistry
                    O

CH3 CH2 CH2 CH2 C       O    CH2 CH3


 Ethyl pentanoate




                            WWU-Chemistry
                H
                        O
                    C

                    O
                            CH3


Methyl cyclohexanecarboxylate


                             WWU-Chemistry
                O

                C    O    CH    CH3

                          CH3

Isopropyl benzoate or 2-methylethyl
  benzoate


                           WWU-Chemistry
       Br            O
      5                   Et
    6   4    3       1O
                 2

Ethyl 5-bromo-3,4-dimethylhexanoate




                               WWU-Chemistry
              Br           O
          5        3             Et
      6        4           1 O
                       2

Ethyl 5-bromo-3,4-dimethyl-2,4-hexadienoate




                                      WWU-Chemistry
   Sect. 19.5 and 19.6:
Nomenclature for amides and
          nitriles

 Skip these sections! Not on test!




                           WWU-Chemistry
                Sect. 19.7: Mechanisms
                    Base hydrolysis of an ester
       Ester
                                                   Na +
            O              addition            O                elimination       O               Na +
                    CH 3                  R             CH 3                              H   O-CH 3
        R       O                                  O                          R       O
                                              HO

Na +        O-H



                                  O                H
 sodium salt
 of carboxylic                                         O-CH 3
                              R       O
 acid
                                          Na +



                                                                                  WWU-Chemistry
    Sect. 19.8/ 19.9: Preparation and
       reactions of acid chlorides
    O                               O

R   C   OH   +   SOCl2          R   C   Cl    +   O   S   O

             thionyl chloride
                                    +   H    Cl


Important!!! Acid chlorides are key
intermediates for making esters, amides
and anhydrides!!!!

                                             WWU-Chemistry
                Preparation of an Ester
      O                             O
                     R
      C           H O               C       R
  R       Cl                                         H-Cl
                                R       O


acid chloride      alcohol          ester




                                            WWU-Chemistry
             Preparation of an Amide
    O                           O
                   R
    C                           C    R
        Cl      H N
R                           R       N             H-Cl
                    H
                                      H
               primary
                            amide
               amine




    O
                   R                O
    C           H N                      R         H-Cl
R       Cl                          C
                    R           R       N
                                          R
                secondary
                amine           amide


                                              WWU-Chemistry
      Preparation of an Anhydride
                      O
      O
                                  O       O
      C         H O       R
  R       Cl                                         H-Cl
                              R       O       R

acid chloride   carboxylic    anhydride
                acid




                                              WWU-Chemistry
   Sect. 19.10: Reducing agents
• Review of reductions on acid chlorides.
• A look at the reduction of all the derivatives
  of carboxylic acids.
• We talked about this in Chapter 16!




                                     WWU-Chemistry
Reactions of sodium borohydride
•   Aldehydes yield primary alcohols
•   Ketones yield secondary alcohols
•   Esters give no reaction!
•   Amides give no reaction!




                                   WWU-Chemistry
  Reactions of lithium aluminum
             hydride
• Aldehydes give primary alcohols
• Ketones give secondary alcohols
• Esters give primary alcohols from the
  carboxylic acid part of the ester (Sect 19.20)
• Amides give primary amines!! (Sect 19.24)



                                    WWU-Chemistry
Sect. 19.11: skip




                    WWU-Chemistry
     Sect. 19.12: carboxylic acid
              derivatives
Esters
Amides
Anhydrides
Nitriles
  All of these functional groups will be
  hydrolyzed in acidic or basic water to give
  the parent carboxylic acid

                                    WWU-Chemistry
Sect. 19.13 and 9.14: Esters




                      WWU-Chemistry
        Esters as Flavoring Substances
    O                                                 O

CH3 C    O     CH2 CH2 CH        CH3   CH3 CH2 CH2 C         O   CH2 CH3

   Isopentyl acetate       CH3           Ethyl butyrate
   banana                                pineapple

         O                                 O

CH3 CH2 C      O       CH2 CH    CH3   CH3 C     O        CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3

   Isobutyl propionate    CH3             Octyl acetate
   rum                                    orange

    O                                                 O

CH3 C    O     CH2 CH2 CH3             CH3 CH2 CH2 C         O   CH3

    Propyl acetate                        Methyl butyrate
    pear                                  apple


                                                                       WWU-Chemistry
                 Fischer Esterification
       O                                 +            O
                                       H
R      C    OH     +   R     OH                 R     C    O    R


                                                     +           O
                                                            H        H




    ESTERIFICATION REACTIONS ARE REVERSIBLE. You need
    to push it to the right (ester) by removing water as it forms.
    This reaction is acid catalyzed



                                                      WWU-Chemistry
Fischer esterification is an acid catalyzed reaction

                                        H                             H                          H
          O           +             O           addition            O           - H+           O
                      H
          C       H                 C       H                     R C O-H                    R C O-H
     R        O                 R       O
                                                                    O                          O
                                                                  H   Et                         Et
     carbon hybridization       H-O-Et
                                                                                       carbon hybridization
     is sp2
                                                                                       is sp3




    H                 H     H                                                           H
  O                     O                        R          O-H                        O
              H+                  - H2O              C                      R                 - H+        O
R C O-H               R C O-H                                                   C
                                                     O-Et                                                 C       Et
  O                     O     elimination                                       O-Et                  R       O
    Et                    Et
                                                            resonance!                               sp2carbon




                                                                                    WWU-Chemistry
Sect. 19.15 and 19.16 -- skip




                       WWU-Chemistry
    Sect. 19.17: Hydrolysis of Esters

      O                                O
                           _
R     C   O   R   +   OH           R   C   O    +   R   O   H

See slide for section 19.7 for mechanism of base hydrolysis
     O                         +       O
                               H
R    C    O   R   +   H2O          R   C   OH   +   R   O   H

    Mechanism of the acid catalyzed hydrolysis reaction is the
    reverse of the Fischer esterification reaction!




                                                    WWU-Chemistry
Sect. 19.18: skip




                    WWU-Chemistry
    Sect. 19.19: Reaction of Esters
    with Organometallic Reagents
    O                                 1) ether
R   C   O   R   +    2 R       MgBr
                                      2) H2O, acid


                OH

            R   C    R     +    MgBr (OR)   +    MgBr (OH)

                R

                                            WWU-Chemistry
                                         Mechanism
  Ester
                                                                      ketone intermediate
                                             Mg Br
       O              addition           O              elimination               O
               CH 3                              CH 3                                         BrMg O-CH 3
   R       O                         R       O                                R       R
                                         R

                                                                          ketone, not
Mg Br-R                                                                   isolated!



                                         Mg Br
      O
                  addition           O               H3O+                 OH
  R       R                      R       R                                    R           HO-CH3 from
                                     R                                R
                                                                          R

Mg Br-R                                                        Tertiary alcohol



  This reaction requires one mole of ester and two moles of a Grignard reagent


                                                                                      WWU-Chemistry
     Sect. 19.20: Reduction of Esters
Lithium aluminum hydride gives the primary alcohol
                                                            Aldehyde
              hydride from                                  intermediate
         H
                 LiAlH4      H
     O                           O                                       H
         Et                          Et
 O             Addition      O               Elimination
                                                                     O



                                                                  O-Et


         H

                             H            H3O+               H
         H                       H                               H

     O                       O                               OH

                                                      also HO-Et from ester

                                                           WWU-Chemistry
Diisobutylaluminum hydride (DibalH) gives the aldehyde


              hydride from

         H    i-butyl
                        Al H
              i-butyl          H
     O                             O                                   H
         Et                            Et
 O             Addition        O            Elimination
                                                                   O



                                                   i-butyl
                                                             Al   O-Et
                                                   i-butyl




                                                 WWU-Chemistry
Sect. 19.21: skip




                    WWU-Chemistry
   Sect. 19.22 and 19.23:
Preparation and Reactions of
          Amides
    O                                 O
        C              Heat           C            R
R           OH                R               NH

    +       R    NH2              +            O
                                          H            H




                                      WWU-Chemistry
Remember, also prepare amides
    from acid chlorides
      O                         O
                   R
      C                         C    R
          Cl    H N
 R                          R       N           H-Cl
                    H
                                      H
               primary
               amine




      O
                   R                O
      C         H N                      R       H-Cl
  R       Cl                        C
                    R           R       N
                                          R
                secondary
                amine



                                              WWU-Chemistry
          Amides, continued
• Keep this section simple, skip the DCC
  stuff




                                  WWU-Chemistry
        Sect. 19.24: Reduction of amides
amides give primary amines with lithium aluminum hydride.
                                                                           protonated
                           hydride from                                    imine
              H                                                            intermediate
                              LiAlH4          H                               H
            NH 2
                                                     NH 2
       O                    Addition                         Elimination          NH 2
                                          H3Al-O
    amide

                                                                              O-AlH3


               protonated
               imine
               intermediate                             H
                       H
                                                       H    NH 2
                            NH 2
                                                   primary amine

                   H



                                                                             WWU-Chemistry
Sect. 19.25 and 19.26: Reactions
          of anhydrides
    O       O                       O                  O
                           R
    C       C        H O            C       R          C
R       O       R              R        O         HO       R


                     alcohol                     carboxylic acid
                                   ester




    O       O           R          O                   O
    C                              C     R
            C        H N                               C
R       O       R        H     R        N         HO       R
                                          H
                    primary    amide             carboxylic acid
                    amine


                                                WWU-Chemistry
     Preparation of aspirin and acetaminophen (Tylenol)
              O
                       H                                      O
                   O                                                  H
                                                                  O                  H3C       O
              O                                                                                    H
               H           H3C       O       CH 3             O                            O
                                 O       O                O       CH 3
     salicylic acid
                                                          aspirin


              H
              N                                                       H
                   H
                                                                      N       CH 3         H3C         O
HO                         H3C       O        CH 3                                                         H
                                                                          O                        O
                                 O       O           HO

                                                     acetaminophen
                                                     (Tylenol)




                                                                          WWU-Chemistry
Sect. 19.27 and 19.28: preparation and reactions of nitriles


                                                         Nitrile
                                +
                                                  SN2
                  Br       Na       C     N
                                                                           C    N

  4-bromobutane                     Carbon is a
                                    better nucleophile     NaBr
                                    than nitrogen



                                        H3O+
                                                                     O-H
                       C   N                                                   NH 3

                                                               O




                                                                   WWU-Chemistry
Base-Promoted Hydrolysis of a
      Nitrile (Part One)
  1)
       R     C       N:       slow                .. _
                                     R    C       N:
              _ ..                       :O       H
               :O         H               ..
                ..
                _
  2)       : N:                                  : NH
                  ..                                     ..          _
       R    C     OH + H2O                 R      C      OH   + OH
                  ..                                     ..


  3)
           : NH                          : NH2
                  ..                             ..      Tautomerism
       R   C      OH                 R    C      O
                  ..                             ..


                                                          WWU-Chemistry
Base-Promoted Hydrolysis of a
      Nitrile (Part Two)
  4)                                          .. _
            :O :                            : O:
                    ..                               ..
       R     C      NH2                 R    C       NH2
            _ ..                            :O       H
             :O      H                       ..
              ..
  5)         .. _
           : O:                             :O :             _
                    ..                                       ..
       R    C       NH2                 R    C           + : NH2

           :O       H                       :O       H
            ..                               ..

  6)
           : O:                                              : O:
                    ..
                           _
                                 ..                                  .. _  ..
       R    C       OH +       : NH                      R       C   O : + NH3
                                                                     ..
                    ..              2

                                                                      WWU-Chemistry
 Sect. 19.29: reduction of nitriles
with lithium aluminum hydride and
             Hydrogen
                                                           NH 2
            1) LiAlH4

  Nitrile
                        2) H3O+           pentylamine

            C   N

                        2 moles of H2
                        Palladium or Platinum


                                                          NH 2



                                        pentylamine


                                                      WWU-Chemistry
The remaining sections will not be
included on the third test.




                              WWU-Chemistry
Sect. 19.30: Fats and oils
     (Triglycerides)
                     O

    O       CH2 O    C    R

R   C   O   C    H   O

            CH2 O    C    R


                      WWU-Chemistry
                    The Fatty Acids
           O                          O                          O

CH3 (CH2)10 C   OH     CH3 (CH2)12 C         OH     CH3 (CH2)14 C        OH
     Lauric acid             Myristic acid              Palmitic acid
           O                                                         O

CH3 (CH2)16 C   OH            CH3 (CH2)7 CH          CH (CH2)7 C          OH
     Stearic acid                                 Oleic acid
                                                         O

  CH3 (CH2)4 CH       CH CH2 CH             CH (CH2)7 C         OH
                       Linoleic acid
                                                                 O

 CH3 CH2 CH        CH CH       CH CH2 CH           CH (CH2)7 C           OH
                           Linolenic acid

                                                               WWU-Chemistry
     Sect. 19.31, 19.33, 19.34
• soaps
• proteins
• condensation polymers




                          WWU-Chemistry
Wallace Carothers- commercialized
        Nylon at DuPont




Source: Michigan State University, Department of Chemistry
http://www.chemistry.msu.edu/Portraits/PortraitsHH_collection.shtml

                                                     WWU-Chemistry
Functional Group Interconversions
                                   R      C    N
                                              H2O
                                         O

                                   R     C     OH
                   R’OH                               OH-
           O                                                       O
                      H2O
    R      C   O       R'          H2O        SOCl2        R       C       O
                              R’OH
                                          O
                                                      OH-
   NH3         NH3                 R      C    Cl              RCOOH
   NR’2H       NR’2H
                            H2O
                                                      RCOOH
           O
                                  NH3
     R     C    NH2               NR’2H                        O               O

           O                                           R       C       O       C   R
                                   NH3
     R     C    NR'2
                                   NR’2H

                                                                   WWU-Chemistry

				
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