2.  Fragrant odors  Basic building block of housing materials  Hormones  Digestion  Vision 2

3.  Carbonyl group › C=O › Aldehydes  RCH=O  Formyl › Ketones  RC=OR’ 3

4.  Aldehydes › IUPAC end in “al” › Common end in “aldeyde” › Carbonyl C is always #1 › Cyclic cpds  Carbaldehyde is ending for most 4

5.  Aldehydes methanal (formaldehyde) ethanal (acetaldehyde) propanal (propionaldehyde) butanal (n-butyraldehyde) 5

6.  Aldehydes 3-methylbutanal 3-butenal 2,3-dihydropropanal (glyceraldehyde) 6

7.  Aldehydes cyclopentanecarbaldehyde (formylcyclopentane) benzenecarbaldehyde (benzaldehyde) 2-hydroxybenzenecarbaldehyde (salicylaldehyde) 7

8.  Ketones › IUPAC end in “one” › Common end in “ketone” › Carbonyl C is never #1, but always gets low number preference › Cyclic cpds  Carbaldehyde is ending for most 8

9.  Ketones propanone (acetone) 2-butanone (ethyl methyl ketone) 3-pentanone (diethyl ketone) 9

10.  Ketones cyclohexanone 2-methylcyclopentanone 3- buten-2-one (methyl vinyl ketone) 10

11.  Ketones acetaphenone (methyl phenyl ketone) benzophenone (diphenyl ketone) dicyclopropyl ketone 11

12.  Formaldehyde › Simplest aldehyde › Manufactured on large scale (8 billion lbs per annum) from catalyzed oxidation of methanol CH 3 OH  CH 2 =O + H 2 › Gas at RT (bp = -21˚C) but cannot be stored in free state due to polymerization › Normally 37% soln called formalin (preservative) › Most used in making of plastics, insulation, particle board, and plywood 12

13.  Acetaldehyde › Boils close to RT (bp = 20˚C) › Made by catalyzed oxidation of ethylene 2 CH 2 =CH 2 + O 2  2 CH 3 CH=O › ~1/2 is oxidized to acetic acid › Remainder used for production of 1- butanol and others. 13

14.  Acetone › Simplest ketone › Large scale production like formaldehyde › Produced from oxidation of propene, isopropyl alcohol, or isopropylbenzene › ~30% used directly, great solvent, H 2 O miscible › Rest used to make stuff like epoxy resins 14

15.  Quinones › Cyclic conjugate diketones › Simplest is 1,4-benzoquinone › All are colored and are thus used often as dyes › Alizarin…used to dye the red coats of the British Army during American Revolution › Vitamin K is required for normal clotting of blood 15

16. 16 1,4-benzoquinone alizarin vitamin K Vitamin K

17.  Oxidation › 1˚ ROH gives aldehyde › 2˚ ROH gives ketone › Cr reagents (PCC) are common 17

18.  Friedel-Crafts Acylation › Recall the rxn? › Makes aromatic ketones 18 benzophenonebenzyl chloride

19.  Hydration of terminal alkynes › Gives methyl ketones › Catalyzed by acid and mercuric ion 19

20.  Many have pleasant odors  Used in the perfume industry  Extremely expensive to gather from natural producers  Chanel No. 5 (my mom’s fave perfume) was first perfume to use synthetic organic chemicals in 1921 20

21. 21 benzaldehydecinnamaldehydevanillin

22.  C atom is sp 2 hybridized  Bond angles?  C=O bond length is 1.24Å (compared to 1.43Å for C-O in ROH and ROR  O is more EN than C › Makes a polar bond 22

23.  Most carbonyl reactions are nucleophilic attacks on the carbonyl C  C=C usually is attacked by an electrophile  Due to polarization, physical properties differ from HC’s and ROH’s › bp’s are higher than HC’s, lower than ROH’s 23

24.  C=O is permanently polarized › Positive part of one molecule is attracted to negative part of another molecule › Dipole-dipole forces, weaker than H-bonds, stronger than LDF 24

25.  C=O’s with low MW are soluble in water › Can form H-bonds with water or ammonia 25

26.  Why does the attack occur?  If rxn occurs in hyroxylic solvent (water or ROH), a proton is usually added to the O 26

27.  Carbonyl cpds are weak Lewis bases due to lone pairs on O  Acids can catalyze the addition of weak nucleophiles to carbonyl cpds through protonation 27

28.  Nucleophiles add reversibly › Good leaving groups, CB of SA  Nucleophiles add irreversibly › Poor LG, CB of WA  In general, ketones are less reactive than aldehydes › Steric…sp 2 v. sp 3, R v. H › Electronic…alkyl groups are electron- donating…ketones have two 28

29.  Alcohols are oxygen nucleophiles › OR goes to C, and H goes to O  Because ROH’s are weak nucleophiles, acid catalyst must be used  Product is a hemiacetal › Contains both alcohol and ether on same C  Addition is reversible 29

30.  Mechanism of hemiacetal formation has 3 steps › Carbonyl O is protonated by acid catalyst › ROH’s O then attacks carbonyl C › Proton is then lost from resulting +O  Each step is reversible 30

31.  Write an equation for the formation of a hemiacetal from acetaldehyde, ethanol, and an acid catalyst. Show each step in the rxn mechanism. 31

32.  Excess ROH means hemiacetals react further to produce acetals  Hydroxyl group of hemiacetal is replaced by an alkoxyl group.  Acetals have two ether groups on same C 32

33.  Mechanism of acetal formation 33

34.  Mechanism of acetal formation 34

35.  Aldehydes that have appropriately located hydroxyl group can exist in equilibrium with a cyclic hemiacetal…5-hydroxypetanal 35

36.  Aldehydes that have appropriately located hydroxyl group can exist in equilibrium with a cyclic hemiacetal…5-hydroxypetanal 36

37.  Cpds with hydroxyl group 4 or 5 C’s from the aldehyde group tend to form cyclic hemiacetals and acetals due to lack of strain  Carbohydrates 37

38.  Ketones also form acetals  If a glycol is used, product is cyclic 38

39.  Summary › Aldehyde or ketone reacts with ROH › Hemiacetal is formed › Further ROH makes acetal 39

40.  Water is an oxygen nucleophile, like ROH’s  Can add reversibly 40

41.  Aside from formaldehyde hydrate most other hydrates cannot by isolated because they lost water…K eq <1  One exception is trichloroacetaldehyde (chloral) › Forms a stable crystalline hydrate, chloral hydrate, CCl 3 CH(OH) 2 › Used as a sedative 41

42.  Grignard reagents act as carbon nucleophiles toward carbonyl cpds › Grignard reagent adds irreversibly to the carbonyl carbon, forming a new C-C bond › Favorable because product (an alkoxide) is a much weaker base than the starting carbanion › The alkoxide can be protonated to give an ROH 42

43.  Useful route to alcohols › Type of carbonyl determines class of ROH › Formaldehyde gives 1˚ ROH’s 43

44.  Other aldehydes give 2˚ ROH’s 44

45.  Ketones give 3˚ ROH’s 45

46.  Other organometallic cpds like organolithium cpds and aceylides react with carbonyl cpds similarly to Grignard reagents 46

47.  HCN adds reversibly to carbonyl group of aldehydes and ketones to make cyanohydrins › Hydroxyl and cyano group attached to same C › Basic catalyst is needed 47

48.  Acetone reacts as follows: 48

49.  Cyanohydrins play important role in the defense system of the millipede › Two-chambered gland like the bombadier beetle › Benzaldehyde cyanohydrin is stored and then converted to a mixture of benzadehyde and hydrogen cyanide and secreted 49

50.  Write an equation for the addition of HCN to benzaldehyde. 50

51.  Ammonia, amines, and other related cpds have a lone pair on the N and thus act as a nucleophile toward a carbonyl C 51

52.  Aldehydes and Ketones are easily reduced to 1˚ and 2˚ alcohols, respectively  Metal hydrides used to reduce › Irreversible nucleophilic attack › LiAlH 4 or NaBH 4 52

53.  The original product is an aluminum alkoxide  Then hydrolyzed by water and acid to give ROH  Net result is addition of H across the C=O 53

54.  Aldehydes are more easily oxidized than are ketones  Oxidation of an aldehyde gives an acid with the same number of C’s  Oxidizing agents include KMnO 4, CrO 3, Ag 2 O 54

55.  Tollens Silver Test › Silver-ammonia complex ion is reduced by aldehydes but not by ketones › If test tube is clean, a mirror forms by the metallic Ag › Used to “silver” glass using formaldehyde (cheap) 55

56.  Aldehydes and Ketones may exist as an equilibrium mixture of two forms › Keto and enol forms › Differ in the location of a proton and a double bond  Tautomerism (Greek…same part) › Structural isomers › Not resonance contributors 56

57.  In order for an enol form to exist carbonyl C must have an H attached to the carbon adjacent to the carbonyl group › Known as the  -hydrogen and is attached to the  -carbon 57

58.  Most simple aldehydes and ketones exist primarily in the keto form › Keto more stable › Acetone, 99.9997% keto form  Phenols have mainly enol form 58

59.  Carbonyl cpds that do not have an  - hydrogen cannot form enols and exist only in keto form 59

60.   -Hydrogen is more acidic than normal H attached to a C › Carbonyl C carries a partial + charge, attracting bonding electrons away from the  -H…make it easy for a base to remove the  -H › Resulting anion is stabilized by resonance…enolate anion 60

61.  Enolate anions may act as carbon nucleophiles  Enolate can add reversibly to the carbonyl group of another aldehyde or ketone…known as aldol condensation  Simplest is the combination of two acetaldhyde molecules due to treatment with an aqueous base 61

62. 62

63.  Step 1…base removes  -H to form enolate anion  Step 2…enolate anion adds to the carbonyl carbon of another acetaldehyde molecule, making a new C-C bond  Step 3…alkoxide ion form in step 2 accepts a proton from the solvent, thus regenerating the OH - needed for the first step 63

64.  3-hydroxyaldehydes are always formed  Since  -C acts as a nucleophile, the product always has just one C between the aldehyde and alcohol C’s  Does not matter how long the C chain is in the starting aldehyde 64

65.  Enolate anion of one carbonyl cpd can be made to add to the carbonyl carbon of another cpd  Consider acetaldehyde and benzaldehyde (has no  -H) when treated with base 65