chapter 5. aldehydes and ketones

1. Chapter 5. ALDEHYDES AND KETONES Objectives Determine the names using structures and structures using names, and describe and explain the properties, preparation methods and reactions of aldehydes and ketones.

4. Structure (Continued) Characteristic feature: C=O group: carbonyl group positive pole on C (electrophilic site) negative pole on O (nucleophilic site)

5. Aldehydes and Ketones (Continued) 5.2. Nomenclature Read #18-3 , pg 806 Properties Read #18-4, pg 809 Spectroscopy Read #18-5, pg 811 Focus: IR, MS, NMR

6. 5.4 Preparation a. Oxidation of primary and secondary alcohols Substrate: primary alcohol (R-CH2OH: reaction site: C & O) Reagent: oxidizing agent, mainly compounds of Cr(6+). Examples: *pyridinium chlorochromate (PCC). Mild, used to prepare aldehydes *CrO3 in aqueous sulfuric acid (Jones reagent) (for ketones) *Na2(or K2)Cr2O7 in aqueous acetic acid (ketones)

7. Oxidation of primary and secondary alcohols(General Pathway)

8. Oxidation of primary and secondary alcohols(Examples)

9. Preparation (continued) b. Ozonolysis of alkenes Substrate: alkenes with at least 1 H around the double bond (reaction site: double bond) Reagents: * O3 (carries excess & energetic O). Role: cleaves the C=C bond. Result: formation of ozonide: a cyclic intermediate * Dimethyl sulfide (DMS). Reduces ozonide to Aldehydes / ketones Products formed: *C with 1 alkyl substituent ------> aldehyde *C with 2 ketone

10. Ozonolysis (General Pathway)

11. Ozonolysis (Examples)

12. c. Acid-Catalysed reaction of Alkynes with mercuric salts Location in textbook: #18-7d, pg 820 Substrates: Terminal alkynes R-C?C-H Reaction: * Electrophilic addition of Hg across the triple bond. Product: most stable carbocation * Hydrolysis of the carbocation intermediate. Product: enol which rearranges to methyl ketone. Products: methyl ketones

13. Reaction of Alkynes with Mercuric Salts (Illustration)

14. d. Hydroboration-Oxidation of Alkynes Location in textbook: pg 821 Substrates: Terminal alkynes R-C?C-H Reagents: * Sia2BH. Di(secondary)isoamylborane. Adds across the triple bond. Too bulky to add twice to the multiple bond and produce alcohols. Result: Alkenyl borane intermediate with B at end of the chain. (Anti-Markovnikov orientation) * H2O2. Reacts with B, decomposes the intermediate. Product: Enol that rearranges to aldehyde. Products: aldehydes.

15. Hydroboration-Oxidation of Alkynes (Illustration)

16. Phenyl Ketone and AldehydesFriedel-Crafts Acylation See Slides 12-13 in Aromatic Electrophilic Substitution chapter. Gatterman-Koch Synthesis: variation of F-C acylation. Reagent: CO with HCl and AlCl3. CO and HCl form H-CO-Cl. Electrophile: H-CO(+) from reaction of H-CO-Cl with AlCl3

17. Friedel-Crafts Acylation (Example)

18. 5.5. Reactions Focus: Nucleophilic Addition. Substrates: R-CO-R'. Reaction site: C of C=O group. Site property: electrophilic. Reagents: Nucleophiles (Nu). Bind to C of C=O group Reaction: incorporation of a Nu on the C

19. a. Addition of H nucleophile (Reduction) Definition: increase in H content of an organic molecule Substrate: R-CO-R'(reaction site: C of C=O group) Reagents: sources of H(-) Most commonly used: * NaBH4, mild, spares C=C bonds * LiAlH4, harsh, reduces all multiple bonds Reaction: Step 1: H(-) binds to C of C=O bond. Result: formation of an alkoxide intermediate Step 2: Protonation of the alkoxide to form an alcohol Products: Alcohols Primary alcohols: formed using aldehydes Secondary alcohols: formed using ketones.

20. Reduction of Aldehydes and Ketones (General Pathway)

21. Reduction of Aldehydes and Ketones (Examples)

22. Reduction of Aldehydes and Ketones (Exercises) Answer questions 18-51 g and h, pg 863

23. b. Addition of C Nucleophiles *1. General Case Substrates: R-CO-R' Reaction site: C of C=O group. Site property: electrophilic. Reagents: R(-)M(+) Reaction site: C with negative charge. Site property: nucleophilic. Examples: * R(-)Li(+): alkyllithium *R(-)(+)MgX: alkyl magnesium halides (Grignard reagents) Reactions: * Step1: C nucleophile binds to the C of the C=O group. Result: an alkoxide * Step 2: Protonation of the alkoxide Products: * Primary alcohols from formaldehyde * Secondary alcohols from aldehydes * Tertiary alcohols from ketones

24. Addition of C Nucleophiles (General Pathway)

25. Addition of C Nucleophiles (Examples)

26. Addition of C Nucleophiles (Exercises) Answer the following questions: #10-38 b and c, pg 456

27. *2. Aldol Condensation Substrates: R-CO-R'(site: C of C=O group) Best substrates: aldehydes, less crowded near C=O group. Reagents:R(R')C(-)-CO-R"M+ (conjugate base of R(R')CH-CO-R“ Reaction:* 1st step = nucleophile binds to C of C=O group. Product: aldol (contains both C=O and OH groups) * 2nd step: elimination of H2O. Product: a,b-unsaturated aldehyde/ketone

28. Aldol Condensation (General Pathway)

29. Aldol Condensation (Example)

30. Crossed Aldol Condensation Substrate: aldehyde/ketone w/o acidic protons Reagent: Conjugate base of an aldehyde/ketone. Product: a,b-unsaturated aldehyde/ ketone

31. Crossed Aldol Condensation (Example)

32. Aldol condensation (Exercises) Answer the following questions * 22-67 a, pg 1093 * 22-67 e, pg 1093

33. *3. Wittig Reaction Substrate: R-CO-R' (Reaction Site: C of C=O group) Reagent: Phosphorus ylide (phosphorane): compound w/ negative charge on C & positive charge on P. Property: C nucleophile Example: H2C(-)-(+)P(Ph)3: Methylenetriphenylphosphorane Reaction: *1: C nucleophile of the ylide binds to the C of the C=O group. Result: formation of betaine intermediate: 4 member cycle including 2 C's, one O and one P *2. Break-down of the betaine to form the product Product: alkene w/ C=C bond in place of the old C=O bond

34. Preparation of the Phosphorus Ylide

35. Reaction of the Phosphorus Ylide (General)

36. Wittig Reaction (Example)

37. Wittig Reaction (Exercises) Answer the following questions: * 18-51 b, pg 863 * 18-56 j, pg 864

38. c. Addition of O NucleophilesHemiacetals and Acetals Substrates: Aldehydes (ketones react poorly). Reaction site: C of C=O group. Site property: electrphilic. Reagents: R-OH (electron pairs on O make it a nucleophile) Reaction Conditions: acidic. Helps start the reactions Reaction requirements: dry conditions to prevent hydrolysis of the product Reactions: * Step 1: H(+) binds to O of C=O group. Result Formation of electrophile. * Step 2: O of R-OH binds to C of C=O bond and releases H(+). Products: * Hemiacetals. * Acetals: formed by reaction of hemiacetal with an additional R-OH. Use of acetals: protection of C=O group for further reaction elsewhere on the molecule.

39. Addition of O Nucleophiles (General Pathway)

40. Acetals (Example)

41. Acetals (Continued) Characteristics of acetals: * Stable in basic conditions * Unstable in acidic conditions. They revert to original aldh/Ket * used to protect C=O group from unwanted reaction. * Formed more easily with aldehydes than ketones. Used to protect aldehyde C=O groups while ketone C=O groups react.

42. Acetals as Protecting Groups (examples)

43. Acetals as Protecting Groups (Exercises) Answer Questions: *18-34b, c, pg 851 * 18-49, pg 862 * 18-51, pg 863.