1. Aldehydes and ketones Dr. Sheppard CHEM 2412 Summer 2015
Klein(2nd ed.) sections: 20.1, 20.2, 20.13, 20.3, 20.4, , 20.6, 23.6, 20.9, 20.10,

2. Outline Preview of Carbonyl Chemistry Aldehydes and Ketones
Nomenclature Review
Properties and Spectroscopy
Preparation
Oxidation
Nucleophilic Addition
Wittig Reaction

3. Carbonyl Chemistry Preview
Carbonyl group

4. Carbonyl Reactivity Generally grouped by reactivity
Aldehydes and ketones
Carboxylic acids and derivatives

5. Structure of Carbonyls
Hybridization of C?
Bond angle around C?
Hybridization of O?
Nucleophilic or electrophilic?
Carbonyls are both Lewis acids and Lewis bases

6. Reactions of Carbonyls
Nucleophilic Addition
Aldehydes and ketones
Chapter 20
Seen already:
Reduction of aldehydes and ketones to form alcohols
Grignard reaction of aldehyde and ketones

7. Reactions of Carbonyls
Nucleophilic Acyl Substitution
Carboxylic acids and derivatives
Chapter 21
Seen already:
Reduction of carboxylic acids and esters to form alcohols
Grignard reaction of esters and acid halides

8. Aldehydes and Ketones Nomenclature Review Properties and Spectroscopy
Preparation
Oxidation
Nucleophilic Addition
Wittig Reaction

9. I. Nomenclature (Review)
Acyclic aldehydes
Parent chain contains carbon of CHO
Suffix is “-al”
CHO carbon is carbon 1 (do not need to show in name)
Cyclic molecules with –CHO substituents
-CHO is bonded to carbon 1 of ring
Add “carbaldehyde” to end of ring parent name

10. I. Nomenclature (Review)
Ketones
Parent chain contains carbon of carbonyl; suffix is “-one”
Number so carbonyl has lowest number
Cyclic ketones carbonyl is carbon 1 of the ring
Common name system:
Name both alkyl groups bonded to carbonyl
Add “ketone”

11. I. Nomenclature (Review)
Order of precedence of functions
Used when more than one functional group in a molecule
Example:
Functional Group
Suffix
(High Precedence)
Prefix
(Low Precedence)
-CO2H
-oic acid -
-CHO
-al
formyl-
-C(O)-
-one
oxo-
-OH
-ol
hydroxy-
-NH2
-amine
amino-
Increasing precedence

12. II. Spectroscopy of Aldehydes and Ketones: IR
Absorption at cm-1 for C=O
Absorptions at 2720 and 2820 cm-1 for aldehyde C-H

13. II. Spectroscopy of Aldehydes and Ketones: NMR
Atoms of or bonded to C=O are deshielded
13C-NMR:
1H-NMR:
Aldehyde signal at d9-10;
Hydrogens adjacent
to C=O at d

14. II. Spectroscopy of Aldehydes and Ketones: MS
Molecule fragments on one side of carbonyl (a-cleavage)
Ex: 5-methyl-2-hexanone

15. II. Physical Properties of Aldehydes and Ketones
Carbonyls are polar
Intermolecular forces of aldehydes and ketones
Dipole-dipole
No hydrogen bonding
Boiling points
Higher than alkanes or ethers; lower than alcohols
Aldehydes typically slightly lower than ketones of the same size
Solubility
Low MW soluble in water; decreases as MW increases

16. III. Preparation Aldehydes
Oxidation of primary alcohols with PCC (section 13.10)
Oxidative cleavage of alkenes (section 9.11)
Hydroboration-oxidation of terminal alkynes (section 10.7)
Uses keto-enol tautomerism

17. III. Preparation Aldehydes Reduction of esters (not in Klein)
Reagent = diisobutylaluminum hydride (DIBALH or DIBAH)
Very low temperature prevents reduction to alcohol

18. III. Preparation Ketones
Oxidation of secondary alcohols (section 13.10)
PCC
H2CrO4 (CrO3 or Na2Cr2O7)
KMnO4
Oxidative cleavage of alkenes (section 9.11)

19. III. Preparation
Ketones
Hydration of alkynes (section 10.7)

20. IV. Oxidation Aldehydes Ketones Oxidized to carboxylic acids
[O] = H2CrO4 reagents or KMnO4
Oxidation does not occur with PCC
Ketones
No oxidation

21. V. Nucleophilic Addition
Nucleophile attacks electrophilic carbon of carbonyl
Something adds across C=O
Nucleophile
O, N, H, C
Anion or neutral

22. V. Nucleophilic Addition
Reaction may be reversible
Reaction is often acid- or base-catalyzed
Acid: makes the electrophile (carbonyl) more electrophilic
Base: makes the nucleophile more nucleophilic
For example: ROH + base → RO-

23. V. Nucleophilic Addition
Mechanism:
Acidic conditions:
Basic conditions:
Product is a racemic mixture if a stereocenter is present

24. V. Nucleophilic Addition
Which are more reactive, aldehydes or ketones?
Steric effects:
Aldehydes have more room
for nucleophilic attack
Electronic effects:
Aldehydes are more electrophilic (larger d+) due to fewer R groups
Exception: benzaldehyde stabilizes d+ through resonance

25. V. Nucleophilic Addition
Oxygen nucleophiles
Water
Aldehyde/Ketone + water → geminal diol (hydrate)
Hydrates are unstable and rarely isolated
Exception = formaldehyde hydrate (formalin)

26. V. Nucleophilic Addition
Acid or base catalyst needed because water is a weak nucleophile
Acid:
Base:

27. V. Nucleophilic Addition
Oxygen nucleophiles
Alcohols
Mechanism 20.5 page 941 in Klein
Two nucleophilic additions and lots of proton-transfer reactions
Alcohol is usually solvent (present in excess), so equilibrium favors product
Water must be removed as it forms to prevent reverse reaction
Acetal + H2O → aldehyde/ketone

28. V. Nucleophilic Addition
Formation of acetal

29. V. Nucleophilic Addition
Applications of hemiacetals/acetals
Carbohydrates
Haworth structure
Formation of glycosidic bonds

30. V. Nucleophilic Addition
Applications of hemiacetals/acetals
Carbonyl protecting groups
Convert aldehyde/ketone to acetal
Acetals are unreactive to bases, Grignard reagents, reducing agents
Acetals are reactive to aqueous acid

31. V. Nucleophilic Addition
How can this reaction occur?
Need to protect ketone so ester (only) can be reduced

32. V. Nucleophilic Addition
Draw a synthetic scheme for the following reaction

33. V. Nucleophilic Addition
Nitrogen nucleophile
Ammonia and 1° amines
Product = imine (Schiff base)
Acid-catalyzed

34. V. Nucleophilic Addition
Mechanism
Nucleophilic addition of NH3 or RNH2, followed by loss of water

35. V. Nucleophilic Addition
Ex: 2,4-dinitrophenylhydrazine

36. V. Nucleophilic Addition
Imines can be reduced to amines
[H] = H2, Ni or
LAH or
NaBH4 or
NaBH3CN
Overall process = reductive amination (section 23.6)
Carbonyl + ammonia → imine → 1° amine
Carbonyl + 1° amine → imine → 2° amine

37. V. Nucleophilic Addition
Reductive amination:

38. V. Nucleophilic Addition
Draw the reductive amination for the reaction of acetaldehyde and methylamine.

39. V. Nucleophilic Addition
Nitrogen nucleophile
2° amines yield enamines
We will not discuss this reaction
3° amines
Do not react with carbonyls

40. V. Nucleophilic Addition
Nitrogen nucleophile
Hydrazine (H2N-NH2)
React the same as R-NH2
Product = hydrazone (as seen with 2,4-DNP)
If reaction is run in base, imine is reduced
Wolff-Kishner Reduction

41. V. Nucleophilic Addition
Hydrogen nucleophiles
Hydride ion from NaBH4 or LiAlH4 (reduction reactions)
Aldehyde → primary alcohol
Ketone → secondary alcohol

42. V. Nucleophilic Addition
Carbon nucleophiles
Grignard reagent (R:- +MgX)
Cyanide ion (-:C≡N); product = cyanohydrin
Acetylide ion (R-C≡C:-)
Can act in the same manner as cyanide ion
Wittig reagent ( )

43. VI. Wittig Reaction Ketone/aldehyde → alkene
A carbon-carbon bond-making reaction
Phosphonium ylide:
Neutral molecule with opposing charges on adjacent atoms
A carbon nucleophile
Formed from the reaction of Ph3P: (a good nucleophile) with a 1° or 2° alkyl halide

44. VI. Wittig Reaction Formation of ylide: Mechanism:
In second step, weakly acidic H atoms can be removed with a strong base (NaNH2, NaH, BuLi)

45. VI. Wittig Reaction Reaction of ylide and carbonyl:
Oxaphosphetane can be isolated at low temperature
Driving force for decomposition of ring is formation of strong P=O bond

46. VI. Wittig Reaction
How could you make this alkene using the Wittig reaction?
Do Wittig reaction handout

47. Synthesis Problem
Propose a synthesis of butane starting with ethanol. Use the Grignard reaction.
Propose a synthesis of butane starting with ethanol. Use the Wittig reaction.

48. Synthesis Problem
Show reagents and experimental conditions necessary to bring about each of the following conversions: