Aldehydes and Ketones

1. Aldehydes and Ketones • Structure and properties • Nomenclature • Synthesis (some review) • Reactions (some review) • Spectroscopy – mass spec, IR, NMR

2. Structure and properties Aldehydes and ketones are the simplest carbonyl containing compounds.

3. Structure and properties The carbonyl carbon and oxygen are sp2 hybridized.

4. Structure and properties The carbon oxygen double bond is very polarized. The dipole moments of aldehydes and ketones are larger than most alkyl halides and ether. u = 2.7 D u = 2.9 D u = 1.9 D The high polarization of the carbonyl is due to the electronegativity of oxygen and the separation of charge in the resonance form.

5. Structure and properties London dispersion Dipole-Dipole Hydrogen bonding The large polarization of the carbonyl functional group produces dipole-dipole interaction between the molecules of aldehydes and ketones.

6. Structure and properties Hydrogen bonding does not occur between aldehyde and ketone molecules. Hydrogen bonding can occur with other molecules such as water, alcohols and amines.

7. Solubility • Soluble in alcohols. • Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O-H or N-H. • Acetone and acetaldehyde are miscible in water. Solubility does decrease with longer chain length (> 4-5 carbons).

8. Naming Ketones (IUPAC) Replace -e with -one. Indicate the position of the carbonyl with a number. For diones, don’t drop the final –e. Just add –dione. Number the chain so that carbonyl carbon has the lowest number. For cyclic ketones the carbonyl carbon is assigned the number 1. -CHO > RCOR > R-OH > R-NH2 > C=C > C=C

9. Naming Ketones (IUPAC) 3-methyl-2-butanone 3-methylbutan-2-one 3-bromocyclohexanone 4-hydroxy-3-methyl-2-butanone 4-hydroxy-3-methylbutan-2-one

10. Naming Ketones (IUPAC)

11. Common Names for Ketones Named as alkyl attachments to -C=O. Use Greek letters instead of numbers. (alpha, beta and gamma) a-bromoethyl isopropyl ketone methyl isopropyl ketone

12. Common Ketones to know: Acetone methyl ethyl ketone (MEK) Acetophenone propiophenone benzophenone

13. Naming Aldehydes • IUPAC: Replace -e with -al. • The aldehyde carbon is number 1. • If -CHO is attached to a ring, use the suffix -carbaldehyde.

14. Examples 3-methylpentanal 2-cyclopentenecarbaldehyde cyclopent-2-en-1-carbaldehyde

15. Examples

16. Name as Substituent On a molecule with a higher priority functional group, C=O is oxo- and -CHO is formyl. Aldehyde priority is higher than ketone. 3-methyl-4-oxopentanal 3-formylbenzoic acid

17. Aldehyde Common Names • Use the common name of the acid. • Drop -ic acid and add -aldehyde. • 1 C: formic acid, formaldehyde • 2 C’s: acetic acid, acetaldehyde • 3 C’s: propionic acid, propionaldehyde • 4 C’s: butyric acid, butyraldehyde. -bromobutyraldehyde 3-bromobutanal

18. Common Aldehyde Formaldehyde acetaldehyde propionaldehyde butyraldehyde Benzaldehyde p-tolualdehyde 2-naphthaldehyde

19. Common Aldehyde Common forms of aldehydes. Formalin is a 40% solution of formaldehyde in water. There are two dry forms of formaldehyde the cyclic trimer trioxane and paraformaldehyde. Trioxane paraformaldehyde Heating these materials convert them to formaldehyde.

20. IR Spectroscopy • Very strong C=O stretch around 1710 cm-1. • Conjugation lowers C=O frequency to 1685-1690 cm-1. • Ring strain raises frequency. (Cycolpentanone 1745 cm-1, cycolpropanone 1810 cm-1 ) • Additional C-H stretch for aldehyde: two absorptions at 2710 cm-1 and 2810 cm-1.

21. NMR Spectroscopy 1H • Aldehyde protons are in the δ9-10 range. • CH3 adjacent to a carbonyl singlet at δ 2.1. • CH2 adjacent to a carbonyl give multiple peaks at δ 2.5.

22. NMR Spectroscopy 13C • Carbonyl carbon singlet in the 175-210 ppm range. • Carbons alpha to the carbonyl are in the 30-40 ppm range.

23. 1H NMR Spectroscopy

24. 13C NMR Spectroscopy

25. Mass Spectroscopy

26. Mass Spectroscopy

27. Mass Spectroscopy

28. Industrial Importance • Acetone and methyl ethyl ketone are important solvents. • Formaldehyde used in polymers like Bakelite. • Flavorings and additives like vanilla, cinnamon, artificial butter.

29. Common aldehydes and Ketones

30. Synthesis Review • Oxidation • 2 alcohol + Na2Cr2O7  ketone • 1 alcohol + PCC  aldehyde • Ozonolysis of alkenes.

31. Synthesis Review • 2 alcohol + Na2Cr2O7  ketone

32. Synthesis Review • 1 alcohol + PCC  aldehyde

33. Synthesis Review • Ozonolysis of alkenes.

34. Synthesis Review • Predict the products of the following reactions.

35. Synthesis Review • Friedel-Crafts acylation of aromatic rings • Acid chloride/AlCl3 + benzene  ketone • Gatterman-Koch • CO + HCl + AlCl3/CuCl + benzene  benzaldehyde

36. Synthesis Review Predict the products.

37. Synthesis Review Predict the products.

38. Synthesis Review • Hydration of alkyne • Use HgSO4, H2SO4, H2O : a methyl ketone is obtained with a terminal alkyne. • Use Sia2BH followed by H2O2 in NaOH for aldehyde.

39. Synthesis Review • Hydration of alkyne Predict the products.

40. Synthesis Review • Hydration of alkyne to an aldehyde

41. Synthesis Using 1,3-Dithiane • Remove H+ with n-butyllithium. • Alkylate with primary alkyl halide, then hydrolyze. R-X is a primary halide or tosylate.

42. Ketones from 1,3-Dithiane After the first alkylation, the second H can be removed using BuLi and the resulting anion react with another primary alkyl halide. Giving a ketone upon hydrolyze.

43. Examples of using 1,3-Dithiane

44. Ketones from Carboxylates • Organolithium compounds attack the carbonyl and form a dianion. • Neutralization with aqueous acid produces an unstable hydrate that loses water to form a ketone. The reaction can be done by first treating with one eq. of LiOH followed by a alkyl/aryl lithium reagent. Consider what is happening in each step (mechanistically how does the reaction work?).

45. Ketones from Carboxylates

46. Ketones from Nitriles • A Grignard or organolithium reagent attacks the nitrile carbon. • The imine salt is then hydrolyzed to form a ketone.

47. Aldehydes from Acid Chlorides A mild reducing agent can reduce an acid chloride to an aldehyde. What would happen if you used LAH? Acid Chlorides are prepared by treating an acid with thionyl chloride (SOCl2). Show the synthesis of benzaldehyde from toluene.

48. Ketones from Acid Chlorides Treatment of an acid chloride with lithium dialkylcuprate (R2CuLi) can also be used to synthesize ketones. Reagent preparation:

49. Ketones from Acid Chlorides How it the lithium reagent made?

50. Nucleophilic Addition The addition of a nucleophile to the carbonyl carbon is the most common reaction of aldehydes and ketones. Note: The carbonyl carbon is an electrophilic center.