Project Overview by GY53Q45


									             Chapter 3
An Introduction to Organic
   Reactions and Their
          Acids and Bases

                Created by
Professor William Tam & Dr. Phillis Chang
                                    Ch. 3 - 1
1.     Reactions and Their Mechanisms

    Almost all organic reactions fall into
     one of four categories:
      ● Substitutions
      ● Additions
      ● Eliminations
      ● Rearrangements

                                              Ch. 3 - 2
● Substitutions

      Characteristic reactions of
       saturated compounds such as
       alkanes and alkyl halides and of
       aromatic compounds (even
       though they are unsaturated)

      In a substitution, one group
       replaces another
                                      Ch. 3 - 3
   Examples

H3C   Br + NaOMe                  H3C   OMe + NaBr

      H       + Br   Br                 Br   + HBr

          H                               CH3
              + CH3Cl                           + HCl

                                                Ch. 3 - 4
● Additions

      Characteristic of compounds
       with multiple bonds

      In an addition all parts of the
       adding reagent appear in the
       product; two molecules become

                                     Ch. 3 - 5
   Examples

H            H                                    Br H
    C    C       +   Br   Br              H       C       C       H
H            H                                    H       Br

                                              Cl Cl
    HC       CH + 2 Cl    Cl          H       C       C       H
                                              Cl Cl

                                                          Ch. 3 - 6
● Eliminations

      In an elimination one molecule
       loses the elements of another
       small molecule

      Elimination reactions give us a
       method for preparing
       compounds with double and
       triple bonds
                                    Ch. 3 - 7
   Examples
    H   CH3                      H           CH3
H   C   C     CH3                    C   C
    H   Br                       H           CH3

                                 + MeOH + NaBr

        H     H
    H   C     C     H                H   C    C     H
        Br Br
                                     + 2H      NH2

                                     + 2 NaBr
                                                   Ch. 3 - 8
   Rearrangements
     ● In a rearrangement a molecule
       undergoes a reorganization of its
       constituent parts
     ● Examples
       H           H           H3C           CH3
           C   C                     C   C
H3C    C           H           H3C           CH3
    H3C    CH3

                                             Ch. 3 - 9
1A. Homolysis and Heterolysis of
    Covalent Bonds
   Homolysis

       A B        bond
                                 A + B
                cleavage         radicals

           Forms free radicals

                                            Ch. 3 - 10
   Heterolysis

      A B       bond
                           A + B
              cleavage       ions

      A B                  A +B

                                    Ch. 3 - 11
   Heterolysis

     ● Normally requires the bond to be
               d +           d-
                  A       B
     ● Usually occurs with assistance

            +         -
           d      d
    Y       A B            Y A +B
                                        Ch. 3 - 12
2.   Acid–Base Reactions

 Many of the reactions that occur in
  organic chemistry are either acid–base
  reactions themselves or they involve an
  acid–base reaction at some stage
 Two classes of acid–base reactions are
  fundamental in organic chemistry
   ● Brønsted–Lowry acid–base reactions
   ● Lewis acid–base reactions

                                    Ch. 3 - 13
2A. Brønsted–Lowry Acids and Bases

 Brønsted–Lowry acid–base reactions
  involve the transfer of protons.
 A Brønsted–Lowry acid is a
  substance that can donate a proton.
 A Brønsted–Lowry base is a
  substance that can accept a proton.

                                   Ch. 3 - 14
   Example
    Base              Conjugate Acid
(H+ acceptor)             of H2O

 H   O    + H   Cl          H   O   H +     Cl
     H                          H

            Acid           Conjugate Base
         (H+ donor)            of HCl
                                          Ch. 3 - 15
2B. Acids and Bases in Water
 Hydronium ion (H3O+) is the strongest
  acid that can exist in water to any
  significant extent: Any stronger acid
  will simply transfer its proton to a
  water molecule to form hydronium ion.
 Hydroxide ion (HO-) is the strongest
  base that can exist in water to any
  significant extent: Any base stronger
  than hydroxide will remove a proton
  from water to form hydroxide ion.
                                   Ch. 3 - 16
   Total ionic reaction

H   O   H + Cl   + Na    O   H   2H    O + Na + Cl
    H                                  H

                         Spectator ions

   Net reaction

        H   O    H   +   O   H        2H   O
            H                              H

                                               Ch. 3 - 17
3.     Lewis Acids and Bases

 Lewis Acids are electron pair acceptors.
 Lewis Bases are electron pair donors.
                      Lewis Base
                    (e⊖ pair donor)

 d-         d+
  Cl    H        +   NH3   Cl   + H   NH3

    Lewis Acid
(e⊖ pair acceptor)
                                      Ch. 3 - 18
                                Lewis Base
                              (e⊖ pair donor)
         d-Cl                              Cl
    d-      +
     Cl Al d      +     NH3           Cl Al     NH3
             Cl                            Cl
                          Lewis Acid
                      (e⊖ pair acceptor)

   In Lewis acid–base theory, the
    attraction of oppositely charged species
    is fundamental to reactivity
                                                Ch. 3 - 19
4.   Heterolysis of Bonds to Carbon:
     Carbocations and Carbanions

     d+        d-   heterolysis
       C   Z                           C    +   Z


     d-        d+   heterolysis
       C   Z                          C     +   Z

                                                Ch. 3 - 20
   Carbocations are electron deficient.
    They have only six electrons in their
    valence shell, and because of this,
    carbocations are Lewis acids.

                 C          +       B            C       B

        carbocation              anion
       (a Lewis acid)       (a Lewis base)

             C          +       O   H        C       O       H
                            H                        H
       carbocation          water
      (a Lewis acid)    (a Lewis base)
                                                             Ch. 3 - 21
4A. Electrophiles and Nucleophiles

   Because carbocations are electron-
    seeking reagents, chemists call them
    electrophiles (meaning electron-

   Electrophiles are reagents that seek
    electrons so as to achieve a stable shell
    of electrons like that of a noble gas.

                                        Ch. 3 - 22
   All Lewis acids are electrophiles.
    By accepting an electron pair from a
    Lewis base, a carbocation fills its
    valence shell.

            C        +      B          C      B

       carbocation         anion
      (a Lewis acid   (a Lewis base)
    and electrophile)

                                           Ch. 3 - 23
   Carbon atoms that are electron poor
    because of bond polarity, but are not
    carbocations, can also be electrophiles.

                    d+ d-
    B        +      C O           B   C    O

Lewis base        Lewis acid

                                          Ch. 3 - 24
 Carbanions are Lewis bases.
 A nucleophile is a Lewis base that
  seeks a positive center such as a
  positively charged carbon atom.

                        d+ d-
     Nu        +        C O           Nu   C   O

    nucleophile     electrophile

          C         +       Nu             C   Nu

     electrophile       nucleophile
                                                   Ch. 3 - 25
5.     How to Use Curved Arrows in
       Illustrating Reactions
    Curved arrows
      ● show the direction of electron flow in a
        reaction mechanism.
      ● point from the source of an electron pair to
        the atom receiving the pair.
      ● always show the flow of electrons from a
        site of higher electron density to a site of
        lower electron density.
      ● never show the movement of atoms.
        Atoms are assumed to follow the flow of
        the electron.                           Ch. 3 - 26
   Examples

      HO        H         NOT    HO         H

                    d-O                     d-O
      N                         N
           H                            H
H                    C     H                    C
      H              d+          H              d+

      O                             O
H3C        O   H+    OH    H3C          O +H         H
                                               Ch. 3 - 27
6.     The Strength of Brønsted–Lowry
       Acids and Bases: Ka and pKa
    In contrast to strong acids such as HCl
     and H2SO4, acetic acid is a much
     weaker acid.
           O                      O

     H3C       OH + H2O     H3C       O   + H   O   H
      ● At 25oC, in a 0.1 M acetic acid solution,
        only about 1% of the acetic acid
        molecules ionize.
                                                Ch. 3 - 28
6A. The Acidity Constant, Ka
          O                      O

    H3C       OH + H2O     H3C       O       + H   O   H

   Equilibrium constant (Keq)
                           ⊖             ⊕
                    [CH3CO2 ]    [H3O ]
          Keq =

                                                   Ch. 3 - 29
   For dilute aqueous solutions, the
    concentration of water is essentially
    constant (~55.5M); and the Keq
    expression can be written in terms of
    the acidity constant (Ka).
                               ⊖         ⊕
                        [CH3CO2 ]   [H3O ]
Ka = Keq [H2O] =

   At 25°C, the acidity constant for acetic
    acid is 1.76 x 10-5.
                                        Ch. 3 - 30
   For any weak acid dissolved in water

 HA + H2O                   H3O      + A
                       ⊕    ⊖
                  [H3O ] [A ]
           Ka =

 An acid with a large value of Ka
   is a strong acid.
 An acid with a small value of Ka
   is a weak acid.
                                      Ch. 3 - 31
6B. Acidity and pKa

                pKa = - log Ka
              pH = - log [H3O ]

   For acetic acid the pKa is 4.75
          pKa = - log [1.76 x 10-5]
              = - [- 4.75]
              = 4.75
                                      Ch. 3 - 32
   The larger the value of the pKa, the
    weaker the acid

            Increasing acid strength

 CH3CO2H           CF3CO2H           HCl
pKa = 4.75     >   pKa = 0     >   pKa = -7
     Weak                               Very
     acid                              strong
                                         Ch. 3 - 33
      Relative Strength of Selected Acids &
       Their Conjugate Bases
                  Increasing acid strength
                        O                  H             H             H
Acid        HCl    Ph    S     OH              H3C   O       H    O        HNO3
                        O                                H             H

p Ka        -7          -6.5        -2.9         -2.5        -1.74         -1.4

            Cl     Ph    S     O                CH3OH            H2O       NO3

                  Increasing base strength
                                                                       Ch. 3 - 34
      (Cont'd)

                       Increasing acid strength
                   O                      O                H                O
Acid                          HF                     Ph    N     H
            F3C          OH         Ph          OH                   H3C          OH
pKa               0.18        3.2        4.21             4.63             4.75

                   O                      O                                 O
                              F                      Ph     NH2
            F3C          O          Ph          O                    H3C          O

                       Increasing base strength
                                                                       Ch. 3 - 35
      (Cont'd)

                 Increasing acid strength
            O         O       H                          H
Acid                      H   N     H              H3C   N   H H O H

                H             H                          H

pKa             9.0           9.2       9.9          10.6       15.7

            O         O                       O
                              NH3                   CH3NH2      HO

                 Increasing base strength
                                                              Ch. 3 - 36
      (Cont'd)

                  Increasing acid strength

                             OH   O
Acid              OH                         HC            H      H        H

pKa          16         18        19.2            25                  35

                             O    O
                  O                           HC       C           H

              Increasing base strength
                                                               Ch. 3 - 37
   (Cont'd)

                Increasing acid strength

                                        H          H
    Acid         H2N    H   H2C             H3C    C     H
                                        H          H

    p Ka           38             44              50

                  NH2       H2C        CH   H3C        CH2

                Increasing base strength
                                                       Ch. 3 - 38
6C. Predicting the Strength of Bases
 The stronger the acid, the weaker its
  conjugate base.
 The larger the pKa of the conjugate
  acid, the stronger the base.
            Increasing base strength
        ⊖                     ⊖                ⊖
      Cl               CH3CO2             HO
Very weak base        Weak base        Strong base

    pKa (HCl)       pKa (CH3CO2H)       pKa (H2O)
      = -7              = 4.75           = 15.7
                                            Ch. 3 - 39
   Example
     Base         CH3OH               H2O

     Conjugate   H3C     O    H   H    O      H
     Acid                H             H

     pKa               -2.5           -1.74

 Since CH3O H2 is a stronger acid than
      ⊕H O is a stronger base than
  H3O , 2
                                              Ch. 3 - 40
7.   How to Predict the Outcome of
     Acid–Base Reactions
 Acid–base reactions always favor the
  formation of the weaker acid and the
  weaker base.
 Acid–base reactions are under
  equilibrium control.
 Reactions under equilibrium control
  always favour the formation of the
  most stable (lowest potential energy)
                                    Ch. 3 - 41
                stronger       weaker
                  base          base
     O                         O
R        O   H + Na   OH   R       O Na + H       H

    stronger                         weaker
      acid                             acid
    pKa ~3-5                        pKa = 15.7

                                          Ch. 3 - 42
7A. Water Solubility as the Result of
    Salt Formation
 Most carboxylic acids containing more
  than 5 carbons are insoluble in water.
 However, due to their acidity, they are
  soluble in aqueous NaOH.
    O                            O
R       O   H + Na   OH      R       O Na + H           H
(R>5 carbons)              Soluble in water
  Insoluble               (due to its polarity
   in water                   As a salt)         Ch. 3 - 43
 Similarly, amines with high molecular
  weights are insoluble in water.
 However, due to their basicity, they are
  soluble in aqueous acids.

R   NH 2 + H   O   H   Cl   R   N   H   Cl + H2O
               H                H
  Water                      Water
Insoluble                   Soluble
                                          Ch. 3 - 44
8.    Relationships between Structure
      and Acidity
                    H–F      H–Cl   H–Br       H–I
Bond Length (Å)     0.92     1.28   1.41       1.60
              pKa   3.2       -7     -9        -10

                          Increasing acidity
    The strength of H–X bond
      ● H–F > H–Cl > H–Br > H–I
       The stronger the H–X bond,
          the weaker the acid.    Ch. 3 - 45
   Thus acidity increases as we descend a
    vertical column in a group in the
    Periodic Table.
                HF        F
Increasing      HCl      Cl       Increasing
  acidity       HBr      Br   -     basicity
                HI        I

         The stronger the acid,
    the weaker the conjugate base.
                                      Ch. 3 - 46
            d-   d+   d-   d+    d-   d+   d-   d+
           H3C—H H3N—H          HO—H       F—H
           2.5 2.1 3.0 2.1 3.5 2.1 4.0 2.1

     pKa    48        38        15.7        3.2

  The higher the electronegativity
    of an atom, the easier it will
     acquire a negative charge.
                                            Ch. 3 - 47
   Thus acidity increases from left to right
    when we compare compounds in the
    same row of the Periodic Table.

               Increasing acidity

      H3C–H    H2N–H      HO–H       F–H

       CH      NH        OH       F
          3           2

               Increasing basicity
                                           Ch. 3 - 48
Acidity increases within a given row
      (electronegativity effect)

             C         N         O        F

                                                 Acidity increases within a
Hydride   (H3C–H)   (H2N–H)   (HO–H)    (F–H)

                                                  (bond strength effect)
  pKa        48        38       15.7     3.2

                                                       given column
                                 S        Cl
                              (HS–H)    (Cl–H)
                                7.0       -7
                                Se        Br
                              (HSe–H)   (Br–H)
                                3.9       -9
                                                    Ch. 3 - 49
8A. The Effect of Hybridization
   (50%                 (33.3%              (25%
s character)         s character)        s character)
     sp                   sp2                sp3
                       H      H           H       H
H    C   C   H             C   C        H C C
                       H           H      H       H

pKa = 25             pKa = 44             pKa = 50

   Having more s character means that the
    electrons of the anion will, on the average,
    be lower in energy, and the anion will be
    more stable.                             Ch. 3 - 50
   Relative Acidity of the Hydrocarbons
                                    H           H           H            H
H       C       C       H       >       C   C       >   H       C    C       H
                                    H           H           H            H

   Relative Basicity of the Carbanions
        H                           H
    H       C       C       H   >       C   C       >   H       C     C
        H               H           H           H

                                                                    Ch. 3 - 51
8B. Inductive Effects
   Inductive effects are electronic effects
    transmitted through bonds.
   The inductive effect of a group can be
    electron donating or electron
   Inductive effects weaken as the
    distance from the group increases
    (effective through three bonds).
                                        Ch. 3 - 52
                                     The C–C
                    H3C        CH3   bond is

               d+         d+         d-
            H3C       CH2            F
               2          1

   The positive charge that the fluorine
    imparts to C1 is greater than that
    imparted to C2 because the fluorine is
    closer to C1.
                                           Ch. 3 - 53
9.     Energy Changes
    The two fundamental types of energy
     are kinetic energy and potential energy.

    Kinetic energy is the energy an object
     has because of its motion; it equals
     one-half the object’s mass multiplied by
     the square of its velocity.
      ● KE = ½m2

                                        Ch. 3 - 54
   Potential energy is stored energy. It
    exists only when an attractive or
    repulsive force exists between objects.

   Chemical energy is a form of potential

   The more potential energy an object
    has, the less stable it is.

                                       Ch. 3 - 55
Potential energy (PE) exists between objects that
either attract or repel each other. In the case of
atoms joined by a covalent bond, the lowest PE state
occurs when atoms are at their ideal internuclear
distance (bond length). Lengthening or shortening
the bond distance raises the PE.
                                              Ch. 3 - 56
9A. Potential Energy and Covalent
   Atoms and molecules possess potential
    energy – often called chemical.
    energy – that can be released as heat
    when they react.

   Because heat is associated with
    molecular motion, this release of heat
    results from a change from potential
    energy to kinetic energy.
                                       Ch. 3 - 57
         H + H                             H       H

           DH o = - 436 kJ mol-1

   The relative
    potential                          H + H

                    Potential Energy
    energies of
    atoms and a                         436 kJ mol-1
    molecule.                          H       H
                                                       Ch. 3 - 58
10. The Relationship between Keq
    and DG°
               DG° = - RT ln Keq
    R is the gas constant = 8.314 J K-1
    T is the absolute temperature in kelvins (K)
 For a reaction to favor the formation of
  products when equilibrium is reached it
  must have a negative value for DG°.
 For reactions with a positive DG°, the
  formation of products at equilibrium is
  unfavorable.                        Ch. 3 - 59
                DG° = DH° - T DS°
            DH° is the enthalpy energy
            DS° is the entropy energy
   A negative value for DH° will contribute to
    making DG° negative and will consequently
    favour the formation of products.
   The more random a system is, the greater is
    its DS°.
   A positive entropy change (from order to
    disorder) makes a negative contribution to
    DG° and is energetically favourable for the
    formation of products.                  Ch. 3 - 60
11. The Acidity of Carboxylic Acids

    H3C       OH          CH3CH2   OH
     Acetic acid            Ethanol

   pKa = 4.75              pKa = 16
 DG° = 27 kJ/mol       DG° = 90.8 kJ/mol

            DG° values are for
           OH proton ionization
                                        Ch. 3 - 61
                                            + H3O
Free Energy Change

                        CH3CO2         DG° = 90.8 kJ/mol
                        + H3O

                     DG° = 27 kJ/mol

                        CH3CO2H           CH3CH2OH
                         + H2O              + H2O
                                                         Ch. 3 - 62
      O                           O
                    + H2O                   + H3O
CH3       O     H           CH3       O
  acetic acid                 acetate

CH3CH2    O     H + H2O     CH3CH2      O   + H3O

      ethanol                 ethoxide

                                            Ch. 3 - 63
   When comparing acidity of organic
    compounds, we compare the stability
    of their conjugate base. The more
    stable the conjugate base, the stronger
    the acid.

                CH3COOH    CH3CH2OH

         pKa      4.75        16

                                      Ch. 3 - 64
11A. The Effect of Delocalization
   The conjugate base acetate is more
    stable (the anion is more delocalized)
    than ethoxide due to resonance
       O                 O               O

CH3        O       CH3       O     CH3        O

     ● Thus, acetic acid is a stronger acid
       than ethanol.
                                         Ch. 3 - 65
11B. The Inductive Effect


 CH3       O <H      CH3CH2      O <H

   Acetic acid              Ethanol

 Stronger acid         Weaker acid

                                      Ch. 3 - 66
11C. Summary and a Comparison of
     Conjugate Acid–Base Strengths
 The greater acidity of a carboxylic acid
  is predominantly due to the ability of
  its conjugate base (a carboxylate ion)
  to stabilize a negative charge better
  than an alkoxide ion, the conjugate
  base of an alcohol.
 The conjugate base of a carboxylic acid
  is a weaker base than the conjugate
  base of an alcohol.
                                     Ch. 3 - 67
 11D. Inductive Effects of Other
      O                       O

     CH3        O <H                CH2       O <H

      pKa = 4.75                    pKa = 2.86

            O                          d-
                              d-              d-
Cl                             Cl
      CH2       O   H + H2O         CH2     O + H3O
                                              Ch. 3 - 68
          O                         O
Cl                          Cl
              O                            O

   The Cl further stabilizes the
    carboxylate anion due to negative
    inductive effect of the Cl.

                                        Ch. 3 - 69
12. The Effect of the Solvent on Acidity

   In the absence of a solvent (i.e., in the gas
    phase), most acids are far weaker than they
    are in solution.
   In solution, solvent molecules surround the
    ions, insulating them from one another,
    stabilizing them, and making it far easier to
    separate them than in the gas phase.
   Solvation of any species decreases the
    entropy of the solvent because the solvent
    molecules become much more ordered as
    they surround molecules of the solute.
                                           Ch. 3 - 70
      O                     O

H3C       OH + H2O    H3C       O   + H   O   H
  Water molecules solvate both the
   undissociated acid (CH3CO2H) and its
   anion (CH3CO2) by forming hydrogen
   bonds to them.
  However, hydrogen bonding to CH3CO2
   is much stronger than to CH3CO2H
   because the water molecules are more
   attracted by the negative charge.
                                      Ch. 3 - 71
13. Organic Compounds as Bases
   If an organic compound contains an
    atom with an unshared electron pair, it
    is a potential base.

H3C   O    + H   Cl        H3C    O   H +       Cl
      H                           H
Methanol                 Methyloxonium ion
                       (a protonated alcohol)

                                            Ch. 3 - 72
R   O     + H   A        R   O   H +     A
    H                        H

Alcohol     Strong   Alkyloxonium ion Weak
             acid                     base

R   O     + H   A        R   O   H +     A
    R                        R

Ether      Strong     Dialkyloxonium Weak
            acid            ion      base
                                       Ch. 3 - 73
        O                       O
                + H   A                 +    A
    R       R               R       R

    Ketone       Strong    Protonated       Weak
                  acid       ketone         base

   Proton transfer reactions like these are
    often the first step in many reactions
    that alcohols, ethers, aldehydes,
    ketones, esters, amides, and carboxylic
    acids undergo.
                                            Ch. 3 - 74
14. A Mechanism for an Organic
 H3C    C     OH + H   O   H +     Cl
        CH3            H

tert-Butyl alcohol   Concentrated HCl
 (soluble in H2O)
                             H3C    C     Cl + 2 H2O
                           tert-Butyl chloride
                           (insoluble in H2O)
                                                 Ch. 3 - 75
   Step 1
       CH3                                      CH3 H
H3C    C       O   H + H   O   H         H3C    C     O      H
       CH3                 H                    CH3
                                                      + H        O
   Step 2
           CH3 H                          CH2
 H3C       C       O   H           H3C    C         + H     O
           CH3                            CH3               H
                                                          Ch. 3 - 76
   Step 3

       CH3                  CH3
H3C    C     +   Cl   H3C   C     Cl
       CH3                  CH3

                                Ch. 3 - 77
15. Acids and Bases in Nonaqueous

H    C   C       H + NH2           H   C    C       +H      NH2
    pKa = 25      (stronger base) (weaker base) pKa = 38

    This reaction cannot be carried using
     water as solvent.

     H       H     + NH2               HO       +    H      NH2
    pKa = 15.7                                      pKa = 38
                                                         Ch. 3 - 78
   Since water is a stronger acid than
    ethyne, NH2 will react with water first
    instead of ethyne.

   When NaNH2 is used, solvent such as
    hexane, Et2O or liquid NH3 can be used
    instead of water.

                                       Ch. 3 - 79
16. Acid–Base Reactions & The Synthesis
    of 2H- & 3H-Labeled Compounds

     Li   +         O                D + OD + Li
              D         D
                                       (weaker base)
           (stronger acid)

Isopropyl lithium           2-Deuteriopropane
 (stronger base)              (weaker acid)
                                                Ch. 3 - 80

                       Ch. 3 - 81

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