1. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 261 Lectures 25 and 26 Carbonyl Compounds I and II Chapter 9

2. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 262 Aldehydes and Ketones Aldehydes and ketones are characterized by the the carbonyl functional group (C=O) The compounds occur widely in nature as intermediates in metabolism and biosynthesis They are also common as chemicals, as solvents, monomers, adhesives, agrichemicals and pharmaceuticals

3. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 263 Naming Aldehydes and Ketones Aldehydes are named by replacing the terminal -e of the corresponding alkane name with –al The parent chain must contain the CHO group – The CHO carbon is numbered as C1 If the CHO group is attached to a ring, use the suffix carboxaldehyde

4. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 264 Naming Ketones Replace the terminal -e of the alkane name with –one Parent chain is the longest one that contains the ketone group –Numbering begins at the end nearer the carbonyl carbon

5. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 265 Ketones with Common Names IUPAC retains well-used but unsystematic names for a few ketones

6. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 266 Ketones and Aldehydes as Substituents The R–C=O as a substituent is an acyl group is used with the suffix -yl from the root of the carboxylic acid –CH 3 CO: acetyl; CHO: formyl; C 6 H 5 CO: benzoyl The prefix oxo- is used if other functional groups are present and the doubly bonded oxygen is labeled as a substituent on a parent chain

7. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 267 Preparation of Aldehydes and Ketones Preparing Aldehydes Oxidize primary alcohols using pyridinium chlorochromate

8. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 268 Preparing Ketones Oxidize a 2° alcohol Many reagents possible: choose for the specific situation (scale, cost, and acid/base sensitivity)

9. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 269 Ketones from Ozonolysis Ozonolysis of alkenes yields ketones if one of the unsaturated carbon atoms is disubstituted

10. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2610 Aryl Ketones by Acylation Friedel–Crafts acylation of an aromatic ring with an acid chloride in the presence of AlCl 3 catalyst

11. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2611 Methyl Ketones by Hydrating Alkynes Hydration of terminal alkynes in the presence of Hg 2+

12. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2612 Oxidation of Aldehydes and Ketones CrO 3 in aqueous acid oxidizes aldehydes to carboxylic acids efficiently Silver oxide, Ag 2 O, in aqueous ammonia (Tollens reagent) oxidizes aldehydes (no acid)

13. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2613 Hydration of Aldehydes Aldehyde oxidations occur through 1,1-diols (hydrates) Reversible addition of water to the carbonyl group Aldehyde hydrate is oxidized to a carboxylic acid by usual reagents for alcohols

14. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2614 Nucleophilic Addition Reactions of Aldehydes and Ketones Nu - approaches the C=O and adds to C A tetrahedral alkoxide ion intermediate is produced

15. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2615 Nucleophiles Nucleophiles can be negatively charged ( : Nu ) or neutral ( : Nu) at the reaction site The overall charge on the nucleophilic species is not considered

16. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2616 Relative Reactivity of Aldehydes and Ketones Aldehydes are generally more reactive than ketones in nucleophilic addition reactions The transition state for addition is less crowded and lower in energy for an aldehyde (a) than for a ketone (b) Aldehydes have one large substituent bonded to the C=O: ketones have two

17. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2617 Electrophilicity of Aldehydes and Ketones Aldehyde C=O is more polarized than ketone C=O As in carbocations, more alkyl groups stabilize + character Ketone has more alkyl groups, stabilizing the C=O carbon inductively

18. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2618 Reactivity of Aromatic Aldehydes Less reactive in nucleophilic addition reactions than aliphatic aldehydes Electron-donating resonance effect of aromatic ring makes C=O less reactive electrophilic than the carbonyl group of an aliphatic aldehyde

19. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2619 Nucleophilic Addition of H 2 O: Hydration Aldehydes and ketones react with water to yield 1,1-diols (geminal (gem) diols) Hyrdation is reversible: a gem diol can eliminate water

20. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2620 Relative Energies Equilibrium generally favors the carbonyl compound over hydrate for steric reasons –Acetone in water is 99.9% ketone form Exception: simple aldehydes –In water, formaldehyde consists is 99.9% hydrate

21. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2621 Base-Catalyzed Addition of Water Addition of water is catalyzed by both acid and base The base-catalyzed hydration nucleophile is the hydroxide ion, which is a much stronger nucleophile than water

22. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2622 Acid-Catalyzed Addition of Water Protonation of C=O makes it more electrophilic

23. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2623 Nucleophilic Addition of Grignard Reagents and Hydride Reagents: Alcohol Formation Treatment of aldehydes or ketones with Grignard reagents yields an alcohol – Nucleophilic addition of the equivalent of a carbon anion, or carbanion. A carbon–magnesium bond is strongly polarized, so a Grignard reagent reacts for all practical purposes as R : MgX +.

24. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2624 Mechanism of Addition of Grignard Reagents Complexation of C=O by Mg 2+, Nucleophilic addition of R :, protonation by dilute acid yields the neutral alcohol Grignard additions are irreversible because a carbanion is NOT a leaving group

25. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2625 Hydride Addition Convert C=O to CH-OH LiAlH 4 and NaBH 4 react as donors of hydride ion Protonation after addition yields the alcohol

26. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2626 Nucleophilic Addition of Amines: Imine and Enamine Formation RNH 2 adds to C=O to form imines, R 2 C=NR (after loss of HOH) R 2 NH yields enamines, R 2 N CR=CR 2 (after loss of HOH) (ene + amine = unsaturated amine)

27. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2627 Mechanism of Formation of Imines Primary amine adds to C=O Proton is lost from N and adds to O to yield a neutral amino alcohol (carbinolamine) Protonation of OH converts into water as the leaving group Result is iminium ion, which loses proton Acid is required for loss of OH – too much acid blocks RNH 2 Note that overall reaction is substitution of RN for O

28. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2628 Imine Derivatives Addition of amines with an atom containing a lone pair of electrons on the adjacent atom occurs very readily, giving useful, stable imines For example, hydroxylamine forms oximes and 2,4- dinitrophenylhydrazine readily forms 2,4- dinitrophenylhydrazones –These are usually solids and help in characterizing liquid ketones or aldehydes by melting points

29. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2629 Nucleophilic Addition of Alcohols: Acetal Formation Two equivalents of ROH in the presence of an acid catalyst add to C=O to yield acetals, R 2 C(OR ) 2 These can be called ketals if derived from a ketone

30. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2630 Formation of Acetals Alcohols are weak nucleophiles but acid promotes addition forming the conjugate acid of C=O Addition yields a hydroxy ether, called a hemiacetal (reversible); further reaction can occur Protonation of the OH and loss of water leads to an oxonium ion, R 2 C=OR + to which a second alcohol adds to form the acetal

31. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2631 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)

32. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2632 The Cannizzaro Reaction: Biological Reductions The adduct of an aldehyde and OH can transfer hydride ion to another aldehyde C=O resulting in a simultaneous oxidation and reduction (disproportionation)

33. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2633 The Biological Analogue of the Canizzaro 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 barrier Enzymes are chiral and the reactions are stereospecific. The stereochemistry depends on the particular enzyme involved.

34. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2634 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

35. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2635 Conjugate Addition of Amines Primary and secondary amines add to, - unsaturated aldehydes and ketones to yield - amino aldehydes and ketones

36. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2636 Conjugate Addition of Alkyl Groups: Organocopper Reactions Reaction of an, -unsaturated ketone with a lithium diorganocopper reagent 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

37. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2637 Mechanism of Alkyl Conjugate Addition Conjugate nucleophilic addition of a diorganocopper anion, R 2 Cu, an enone Transfer of an R group and elimination of a neutral organocopper species, RCu

38. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2638 Biological Nucleophilic Addition Reactions Example: Many enzyme reactions involve pyridoxal phosphate (PLP), a derivative of vitamin B6, as a co-catalyst PLP is an aldehyde that readily forms imines from amino groups of substrates, such as amino acids The imine undergoes a proton shift that leads to the net conversion of the amino group of the substrate into a carbonyl group

39. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2639 Summary Aldehydes are from oxidative cleavage of alkenes, oxidation of 1° alcohols, or partial reduction of esters Ketones are from oxidative cleavage of alkenes, oxidation of 2° alcohols, or by addition of diorganocopper reagents to acid chlorides. Aldehydes and ketones are reduced to yield 1° and 2° alcohols, respectively Grignard reagents also gives alcohols 1° amines add to form imines, and 2° amines yield enamines Alcohols add to yield acetals -Unsaturated aldehydes and ketones are subject to conjugate addition (1,4 addition)

40. C 2004 Barry Linkletter, UPEI Chemistry 243 - Lecture 25 and 2640 For Next Class Read Chapter 10 –Carboxylic Acids and Their Derivatives