Organic Chemistry II Aldehydes and Ketones - PowerPoint

Document Sample
Organic Chemistry II Aldehydes and Ketones - PowerPoint Powered By Docstoc
					                Organic Chemistry II

               Aldehydes and Ketones


                      Dr. Ralph C. Gatrone
               Department of Chemistry and Physics
                     Virginia State University



Spring, 2008                                         1
               Chapter Objectives
•   Nomenclature
•   Preparation
•   Reactions
•   Spectroscopy




Spring, 2008                        2
               Nomenclature
• Aldehydes
• Identify the alkane
• Parent alkane must contain the CHO
  group
• CHO group C is numbered 1
• Replace the “e” with “al”


Spring, 2008                           3
                           Examples
                                O
                     4                           1
                                                     O
                                1 H
                                                 H



               4-butyloctanal         3-phenylbutanal



Spring, 2008                                             4
               Nomenclature
• Aldehydes
• Aldehyde carbon is bonded to ring
• Suffix used is “carbaldehyde”




Spring, 2008                          5
                         Examples
               O
                                             O
                   H                             H



   benzenecarbaldehyde    cis-2-methylcyclopentanecarbaldehyde




Spring, 2008                                                     6
                         Common Names
                     O
                                 formaldehyde                  H
                 H           H                                     valeraldehyde
                                                           O
                     O
                                 acetaldehyde      O
               H3C           H
                                                       H           acrolein

                     O
                                 propionaldehyde   O
        CH3CH2           H
                                                       H           crotonaldehyde
                     O
                                 butyraldehyde
                         H                             O

                     O                                     H

                             H benzaldehyde                    cinnamaldehyde



Spring, 2008                                                                        7
               Nomenclature
•   Ketones
•   Identify the alkane
•   Parent alkane
•   The longest chain containing the carbonyl group
•   The carbonyl C gets the lowest number possible
•   Replace the “e” with “one”




Spring, 2008                                          8
                          Examples

                      O
                                                    O
               3-heptanone      (E,E)-nona-5,7-dien-2-one



                  O                         O
                       O



          1,2-cyclohexandione         2-cyclohexenone
Spring, 2008                                                9
               Nomenclature
• If present with another functional group
• Prefix “oxo” is used

                               O



                    O

                4-oxohexanal


Spring, 2008                                 10
               Common Names

                       O           O
     O


acetone        acetophenone   benzophenone




Spring, 2008                                 11
               As a Substituent
• When R-C=O is used as a substituent
• Referred to as an acyl group
• Ending “yl” is used

                                   O
                O



               acetyl        benzoyl
Spring, 2008                            12
                                     Preparation
• [O] of primary ROH
                               PCC/CH2Cl2

                       OH                              O



• [H] of RCO2H
                                                o
                         OH 1. DIBAH/toluene/-78 C

                     O        2. H3O+                      O



• [O] of secondary ROH
                  OH         [O]                   O



        many reagents can be use
        cost, scale, sensitivity to acid or base

Spring, 2008                                                   13
                       Preparation
• Ozonolysis of Alkenes
                 R    H     1. O3        R       H

                            2. Zn/HOAc       O
          must have one H




Spring, 2008                                         14
               Hydration of Alkynes
• Hydration of terminal alkynes in the presence of
  Hg2+ (catalyst)




Spring, 2008                                     15
                       Preparation

 From Organometallics

                   O           R2CuLi                 O

               R       Cl                         R       R

                       R2CuLi from RLi and CuCl

                   O           R2Cd                   O

               R       Cl                         R       R

                       R2Cd from RLi and CdCl2


Spring, 2008                                                  16
                            Preparation
• Friedal-Crafts Acylation
                    O            O
               R           Cl
                                     R

                   AlCl3

• Recall:
• Reaction does not occur
  on deactivated rings



Spring, 2008                              17
                       Reactions
• Oxidation of Aldehydes
               O                 O
                       [O]
      R            H         R       OH
• [O] = KMnO4/acid; hot HNO3, and CrO3/acid

• Ketones are generally inert to oxidation


Spring, 2008                                  18
                   Reactions
                                   -
               O               O

                               +

• Resonance contribution
• Carbon is electrophilic
• Oxygen is nucleophilic

Spring, 2008                           19
               Nucleophilic Addition
                                            -
                     O                  O


                                        Nu



               Nu:

• Provides a tetrahedral intermediate
Spring, 2008                                    20
Spring, 2008   21
    The Tetrahedral Intermediate
                             OH
                    HA   R
         O               R    Nu
     R
     R         Nu                       H +
                    HA       OH    HA     OH     -H2O       Nu
                         R              R
                         R              R   Nu          R        R
                              Nu


• Aldehydes are more reactive than ketones
• Consider several nucleophiles

Spring, 2008                                                22
               Nucleophile = Water
•   Product is a 1,1-diol, a gem-diol, a hydrate
•   Reaction is equilibrium process
•   Position of equilibrium depends upon structure
•   Reaction is readily reversible

               O
                                     HO      OH
          R        R                  R       R

Spring, 2008                                         23
                   Equilibrium Process
                   O         H2O                 OH

               R       H                    R         H
                                                 OH


                   O          H2O                OH

               R       R                     R        R
                                                 OH
                   when R=R=H 99.9% hydrate
                   when R = R = CH3 99.9% carbonyl

Spring, 2008                                              24
               Nucleophile = Y in HY
• Reaction of C=O with H-Y, where Y is
  electronegative, gives an addition product
• Formation is readily reversible




Spring, 2008                                   25
                    Nu = HCN
               Cyanohydrin Formation
• HCN – very weak acid
   – pKa = 9.1
   – Equilibrium favors HCN
   – Availability of CN as nucleophile is reduced
   – Base catalysis favors cyanohydrin formation




Spring, 2008                                        26
                Uses of Cyanohydrins
• The nitrile group (CN) can be reduced with LiAlH4 to
  yield a primary amine (RCH2NH2)
• Can be hydrolyzed by hot acid to yield a carboxylic acid




 Spring, 2008                                                27
 Nucleophile = Organometallic Reagent

• Grignard reagent




• Effectively a carbanion

Spring, 2008                        28
                Grignard Additions
      O                       O        MgX+                OH
                          R        H                   R        H
  R        H
               R'   MgX       R'              H3O+         R'
                                                     secondary alcohol


      O                       O        MgX+                OH
                          R        R"                  R        R"
  R       R"
               R'   MgX       R'              H3O+         R'
                                                     tertiary alcohol




Spring, 2008                                                            29
               Nucleophile = Hydride
• Reduction of Carbonyl compounds
• Can use NaBH4 or LiAlH4




Spring, 2008                           30
               Hydride Addition
•   Convert C=O to CH-OH
•   LiAlH4 and NaBH4 react as donors of hydride ion
•   Source of H-1 (not real but useful formally)
•   Protonation after addition yields the alcohol




Spring, 2008                                      31
                   Nucleophile = Amine
               Imine and Enamine Formation
• Amines – organic derivatives of ammonia
• Classified by number of substituents on N
                                    ..
                                    N
                               H         H
                                  H
                               ammonia

                      ..            ..           ..
                      N             N            N
                  R        H    R        R   R        R
                      H             H            R

                 primary        secondary    tertiary
• Primary and Secondary amines react
• Tertiary amines do not react with carbonyls
Spring, 2008                                              32
Spring, 2008   33
               Imines and Enamines
•   Requires an acid catalyst
•   pH dependent reaction
•   Reaction is slow at high and low pH
•   At high pH – not enough acid to protonate
•   At low pH – the amine is protonated




Spring, 2008                                34
Spring, 2008   35
   Imine Formation is Reversible
• Drive reaction to right
     – Add excess amine
     – Remove water
• Dean Stark Trap
     – Removes water
     – Azeotrope formation




Spring, 2008                       36
                     Derivatives of Imines
• Hydroxylamine (NH2OH)
            O
                      NH2OH     NOH
        R       R'
                       H+     R    R'
                               oxime

• Hydrazine (NH2NH2)
        O
                     NH2NH2        NNH2
    R           R'
                        H+      R     R'
                               hydrazone

Spring, 2008                                 37
                      Uses of Oximes
• Beckmann rearrangement
• Synthesis of Nylon

                                 H
               NHOH              N     O
                        H+
                                           Nylon



                             caprolactam



Spring, 2008                                       38
                  Uses of Hydrazones
               The Wolff–Kishner Reaction
• Reduction under basic conditions
• Ketone or Aldehyde into an alkane
• Originally carried out at high temperatures but
  with dimethyl sulfoxide as solvent takes place
  near room temperature




Spring, 2008                                        39
            Uses of Hydrazones
         The Clemmensen Reduction
 • Reduction under acidic conditions

               NNH2                H H
                 R    Zn(Hg)/HCl         R




 • Provides alkane from Ketone/aldehyde
 • Through Hydrazone

Spring, 2008                                 40
                Uses of Hydrazones
               Reduction of Carbonyls
• Reduction under neutral conditions
     – Tosylhydrazone

                     NaBH3CN

                      O
                              NNH2
    O                     S          TsNHN
                              O
               H3C




Spring, 2008                                 41
               Nucleophile = Alcohol
• Two equivalents of ROH and acid catalyst
• Acetal formation

                 O                             OR
                          ROH/H+
                                               OR

                           H3O+


                     HO               H+   O
                 O               OH
                                               O

                          H3O+
Spring, 2008                                        42
                Uses of Acetals
• Acetals can serve as protecting groups for aldehydes
  and ketones
• It is convenient to use a diol, to form a cyclic acetal (the
  reaction goes even more readily)




Spring, 2008                                                     43
               Uses of Acetals
• Thioacetals
• Prepared in same manner as acetals
• Reduction under neutral conditions

               HS          SH           Raney Ni
                                S
                    acid
  O                                 S




Spring, 2008                                       44
           Acetals and Hemiacetals
• Common in carbohydrate chemistry
       CH2OH
           O                  OH       HOCH2    O    OH
 HO        H
                         O         CH2OH   +    HO
   H       OH                                        CH2OH
                   HO         OH
   H      OH      OH
                                               OH
       CH2OH
                   PYRANOSE
                                               FURANOSE
   D-Fructose           72%                      28%




Spring, 2008                                                 45
                     Glucopyranoses

                                             OH
                OH                                   O
                         O
                                       HO
 HO                                                         H
                                  OH    HO           OH
      HO                 OH
                                                           OH
                              H
               -D-Glucose                   -D-Glucose




Spring, 2008                                                46
                   Glucose
-D-glucopyranose
• mp = 146 oC and [] = +112.2o

-D-glucopyranose
• mp = 148 - 155 oC and [] = +18.7o

• Dissolve either in water, mutarotation occurs
• Alpha become beta, beta becomes alpha
• Equilibrium mixture results (37:63 :)

Spring, 2008                                      47
    Some Phosphorus Chemistry
• Amines react with alkyl halides
     – Quaternary ammonium salt
          ..                        R
        R N R          RX               +
                                  R N R         X-
               R                    R

• Phosphines also react with alkyl halides
             ..                             R
           R P R            RX                  +
                                    R P R            X-
                   R                        R
Spring, 2008                                              48
               Phosphorus Chemistry
• Positive charge on P stabilizes negative charge on an
  alpha C
               R                       R
                   +        base           +
        R P R          X-           R P R
               CH2R                   - CHR
                                     an ylid



          alpha carbon
• Ylides are nucleophilic
• React with carbonyl compounds

Spring, 2008                                              49
     Nucleophile = Phosphorus Ylide
          The Wittig Reaction
                     O
         R                       -
             +   R       R           O + PR3          O   PR3            H
      R P R                                                     R
                             R          CHR               CHR
                                                  R
        - CHR                    R                  R           R        CHR
       an ylid                   betaine       oxaphosphetane        +
                                                                    R3P=O



• Extends carbon chain by one carbon atom

• Adds a double bond into system

• Known to be able to control stereochemistry of double
  bond
 Spring, 2008                                                               50
    Nucleophile = Phosphorus Ylide
         The Wittig Reaction
• Generally use triphenyl phosphine
• Triphenylphosphine oxide is very stable
  thermodynamically
• Formation of P=O releases energy




Spring, 2008                                51
       Uses of the Wittig Reaction
• Can be used for monosubstituted, disubstituted, and
  trisubstituted alkenes but not tetrasubstituted alkenes
• For comparison, addition of CH3MgBr to cyclohexanone
  and dehydration with, yields a mixture of two alkenes




Spring, 2008                                            52
                      Brief Review
• Aldehydes and ketones react with Nu
• sp3 intermediate forms
• Intermediate may
    – Reverse to give SM
    – Accept proton to form addition product
    – Eliminate water to form new Nu=C species
• If derivative of carboxylic acid, also may

          O                            -
                     Nu:           O                    O
    R           X              R           X        R       Nu
                                    Nu
• See details of this chemistry in Chapter 16
• Elimination of X does not occur when X = H or R
 Spring, 2008                                                53
          Consider Leaving Groups
• Hydroxide (HO-) is a poor leaving group
   – Generally forms water in order to leave
• Hydride (H-) very poor leaving group
   – An exception found in Cannizzaro Reaction
   – Aldehydes with no alpha hydrogens react

                 gamma H          H alpha
                                         H

                              H      O
                             beta
Spring, 2008                                     54
               The Cannizzaro Reaction
• Cannizzaro observed reaction in strong basic media
• Td intermediate transfers hydride to another aldehyde
• REDOX reaction




Spring, 2008                                              55
      The Biological Analogue of the
          Cannizzaro Reaction
• Enzymes catalyze the reduction of aldehydes and
  ketones using NADH as the source of the equivalent of
  H-
• The transfer resembles that in the Cannizzaro reaction
  but the carbonyl of the acceptor is polarized by an acid
  from the enzyme, lowering the energy barrier

                                       Enzymes are chiral
                                       and the reactions are
                                       stereospecific. The
                                       stereochemistry
                                       depends on the
                                       particular enzyme
                                       involved.
Spring, 2008                                                   56
    Conjugate Nucleophilic Addition to ,-
     Unsaturated Aldehydes and Ketones
     • A nucleophile can
       add to the C=C
       double bond of an
       ,-unsaturated
       aldehyde or ketone

     • conjugate addition,
       or 1,4 addition

     • The initial product is
       a resonance-
       stabilized enolate
       ion, which is then
       protonated



Spring, 2008                                  57
               Conjugate Addition
• Resonance explains conjugate addition
                                           -                    -
               O                       O                    O

                                       +
                                                                    +

                   positive charge designates electrophilic site


• Certain Nu: will add in 1,2 manner
• Other Nu: add 1,4 manner


Spring, 2008                                                            58
    Conjugate Addition of Amines
• Primary and secondary amines add 1.4 to , -
  unsaturated aldehydes and ketones to yield -
  amino aldehydes and ketones




Spring, 2008                                      59
  Conjugate Addition of Alkyl Groups:
      Organocopper Reactions
• Reaction of an , -unsaturated ketone with a lithium
  diorganocopper reagent gives 1,4 addition
• Diorganocopper (Gilman) reagents from by reaction of 1
  equivalent of cuprous iodide and 2 equivalents of
  organolithium
• 1, 2, 3 alkyl, aryl and alkenyl groups react but not
  alkynyl groups




Spring, 2008                                            60
               Other Additions
• Grignards add 1,2 and 1,4 to , -
  unsaturated ketones
• Organo lithium reagents add 1,2 to , -
  unsaturated ketones
• Cyanide ion adds 1,4 to , -unsaturated
  ketones



Spring, 2008                                 61
                Summary of Reactions
• Aldehydes - from oxidative cleavage of alkenes, oxidation of 1°
  alcohols, or partial reduction of esters
• Ketones - from oxidative cleavage of alkenes, oxidation of 2° alcohols,
  or by addition of diorganocopper or organocadmium reagents to acid
  halides .
• Aldehydes and ketones - reduced to yield 1° and 2° alcohols ,
  respectively
• React with Grignard reagents giving alcohols
• Addition of HCN yields cyanohydrins
• 1° amines add to form imines, and 2° amines yield enamines
• Reaction with hydrazine gives hydrazones
   – Reduction of hydrazone in base yields an alkane
   – Reduction of hydrazone in acid/Zn yields an alkane
• Alcohols add to yield acetals
• Phosphoranes add to aldehydes and ketones to give alkenes (the
  Wittig)
• -Unsaturated aldehydes and ketones are subject to conjugate
  addition (1,4 addition)
 Spring, 2008                                                         62
               Infrared Spectroscopy
• C=O
• Strong absorption 1660 – 1770cm-1
• See next two spectra




Spring, 2008                           63
Spring, 2008   64
               NMR Spectroscopy
•   The aldehyde H resonates at 10d
•   Coupling is observed with adjacent H
•   J = 3Hz
•   H adjacent to C=O are slightly deshielded
•   Resonate near 2.0 to 2.3d
•   Methyl ketones are distinctive (2.1d)
•   See next spectrum

Spring, 2008                                    65
Spring, 2008   66
               NMR Spectroscopy
• C=O carbons resonate between 190 –
  215d
• See next spectra




Spring, 2008                           67
Spring, 2008   68
               Mass Spectrometry
• A g H leads to McClafferty rearrangement




• Positive charge remains with O fragment


Spring, 2008                                 69
               Mass Spectrometry
  cleavage is also observed




• See next spectrum


Spring, 2008                       70
Spring, 2008   71