MAJOR REACTIONS OF ALDEHYDES AND KETONES AT THE ALPHA- CARBON

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					CHEM. 118B WORKSHOP/LSC/DOUG KENT & JIM HOLLISTER

MAJOR REACTIONS OF ALDEHYDES AND KETONES AT THE ALPHA-
CARBON (FROM CHAPTER 18, VOLLHARDT & SCHORE, 4th ED.)

Name                       Type of Reaction            Reagents,           Product(s)         Comments
                                                       Catalysts,
                                                       Solvents, etc.
1. a-halogenation          a-alkylation                X2/ H+              a-halogenated      1. monohalogenation with acid.
   (in acid)                                           (X = Cl or Br)      carbonyl cmpd.     2. when followed by KOH, makes
                                                                                                 a, b- carbonyl compound.
2. a-halogenation          a-alkylation                X2 / OH-            a-halogenated      multiple halogenations with base
   (in base)                                           (X = Cl, Br or I)   carbonyl cmpd.
3. haloform reaction       1a) a-alkylations;          1) 3 X2 / OH-       carboxylic acid    qualitative test for methyl ketone;
   on methyl ketones       1b) nucleophilic                                and CHX3           messy with other carbonyl
   (works on                                           2) H+ /H2O                             compounds.
                               addition/elimination                        (haloform) with
   CH3CHO too)             2) acid work-up                (X = Cl, Br or   methyl ketone
                                                           I)
4. a-alkylation            1) acid/base rxn.           1) strong base      a-alkylated        1. ketone can yield multiple
   of ketones              2) Sn2 (enolate                 as LDA          carbonyl cmpd.        alkylation products. Best if start
   (same as enolate           attacks RX)              2) RX (CH3                                with disubstituted a-carbonyl.
    alkylation)                                            or 1o)                             2. won’t work with aldehydes (get
                                                                                                  aldol-condensation instead).
5. a-alkylation            1) make enamine             1) R'2NH/ H+        a-alkylated        1. avoids multiple alkylations
    of aldehydes &         2) Sn2 (enamine attacks     2) RX (CH3,         carbonyl cmpd.     2. works with aldehydes & ketones
   ketones via                RX)
    enamine (same as                                      1o, or 2o)
                           3) hydrolysis (of iminium
   enamine alkylation)        salt)                    3) H+ / H2O
6. aldol-condensation      acid/base reaction;          1) OH-             a, b-unsaturated   1. initial product before dehydration
                           condensation;                2) D               carbonyl cmpd.         (D) is a b-hydroxycarbonyl cmpd.
                           dehydration                                                            (aldol adduct)
                                                                                              2. reversible reaction; with base cat.,
                                                                                                 modest yield of aldol from
                                                                                                  aldehydes; poor yield from
                                                                                                  ketones.
7. crossed aldol           same as above               same as above       same as above      Useful only if one aldehyde has no
   condensation                                                                               enolizable a-H. Add enolizable
                                                                                              aldehyde slowly to non-enolizable
                                                                                              aldehyde/OH-
8. intramolecular aldol-   same as above               same as above       same as above      1. works with aldehydes and ketones
   condensation                                        (D may not be                           2. favors unstrained 5 & 6-mem-
                                                       required)                                  bered rings.
The following reactions start with an a,b-unsaturated carbonyl compound plus the indicated reagents
Name                    Type of Reaction               Reagents,        Product(s)            Comments
                                                       Catalysts,
                                                       Solvents, etc.
9. Catalytic            Hydrogenation/reduction        H2, Pd-C         carbonyl cmpd.        “1,2”-addition
   Hydrogenation
10. Halogenation        Polar addition to an alkene    X2, CCl4         a, b-dihalo-          “1,2”-addition
                                                                        carbonyl cmpd
11. + 1o amine          Polar addition to a carbonyl   ZNH2/ H+         a, b-unsaturated      “1,2”-addition
      derivative (as    compound                       (Z = OH, RNH,    oxime, hydrazone,
      hydroxylamine,                                                    semicarbazone, etc.
                                                       NHC(O)NH2 ,
      hydrazine, etc)
                                                       etc.)
12. + alkyllithium      Polar addition to a carbonyl   1) RLi           a, b-unsaturated      “1,2”-addition; avoid using
      reagents          compound                       2) H+ /H2O       alcohol               Grignard Reagents with a,b-
                                                                                              unsaturated carbonyl compounds
13. + “HCN”           Conjugate Addition of            KCN/ H+          b-cyanocarbonyl       “1,4-addition”
    (Hydrogen Cyanide HCN                                               compound
     Addition)

14. Hydration           Conjugate Addition of          -
                                                           OH/ H2O      b-hydroxycarbonyl “1,4-addition”
                        HOH                                             cmpd.

15. ”Alcoholation”      Conjugate Addition of          -
                                                           OR/ ROH      b-alkoxylcarbonyl     “1,4-addition”
                        ROH                                             cmpd.

16. + 1o and 2o amine   Conjugate Addition of          RNH2/ H+ or      b-aminocarbonyl       “1,4-addition”
    (Amine Addition)    Amine                                           cmpd.
                                                       R2NH/ H+
17. + lithium dialkyl- Conjugate Addition of R         1) R2CuLi        b-alkylated           “1,4-addition”
     cuprate reagent (I) and H                         2) H+ / H2O      carbonyl cmpd.

18. + lithium dialkyl- Conjugate Addition of           1) R2CuLi        a, b-dialkylated      “1,4-addition”
    cuprate reagent (II) R and R'                      2) R'X           carbonyl cmpd         (R on b- carbon,
                                                                                              R' on a-carbon)
19. Michael Addition    Conjugate Addition of          1) aldehyde or   1,5-dicarbonyl        “1,4-addition”
                        enolate ion                       ketone/base   cmpd. ( also called
                                                       2) H+ / H2O      Michael Product or
                                                                        Michael Adduct or
                                                                        d-dicarbonyl
                                                                        cmpd.)
20. Robinson           Internal Aldol Condensation -OH (often heat   a, b-unsaturated   forms new six membered ring.
    Annulation (or     of Michael Adduct           not necessary)    dicarbonyl cmpd.
  Robinson Annelation) (Michael Product)