CHAPTER 13 ALDEHYDES AND KETONES

Transcription

1 APTE 13 ALDEYDES AND KETNES 1

2 Aldehyde STUTUE =, alkyl, aryl Ketone ' and ' = alkyl or aryl and ' cannot be hydrogen! 2

3 3 NMENLATUE

4 IUPA Nomenclature of Ketones hoose the longest continuous carbon chain that contains the carbonyl carbon Number from the end of the chain closest to the carbonyl carbon Ketone ending is one. The number of carbonyls is indicated with dione, trione,etc. 4

5 EXAMPLES Pentanone Ethyl-3-hexanone

6 2,4-pentanedione Isopropylcyclopentanone or 3-(1-Methylethyl)cyclopentanone 6

7 KETNES ommon, or Trivial, Names Name each group attached to the carbonyl group as an alkyl group ombine into a name, according to the pattern: alkyl alkyl ketone NTE: This is not all one word! 7

8 Example of ommon Names Methyl propyl ketone Diethyl ketone 8

9 3 3 dimethyl ketone acetone A common laboratory solvent and cleaning agent SPEIAL ASES diphenyl ketone benzophenone 3 methyl phenyl ketone 9 acetophenone

10 IUPA Nomenclature of Aldehydes hoose the longest continuous carbon chain that contains the carbonyl carbon Number from the end of the chain closest to the carbonyl carbon (carbon #1!) Aldehyde ending is -al 10

11 EXAMPLES aldehyde group is always carbon 1 pentanal l chloro-3-methylbutanal 11

12 ommon Names of the Aldehydes Formaldehyde Acetaldehyde Propionaldehyde Butyraldehyde Valeraldehyde aproaldehyde 12 6

13 SPEIAL ASES formaldehyde 3 benzaldehyde acetaldehyde 13

14 Forming ommon Names of Aldehydes USE F GEEK LETTES ω ε δ γ β α. ω is always the end of the chain, no matter how long l l 14 ( 2-chlorohexanal ) ( α-chlorohexanal ) ( ω-chlorohexanal )

15 Examples 15 1,4-cyclohexanedione 3-hydroxypentanal 2-cyclopentenone 3-phenylpropanal β phenylproionaldehyde

16 Spectral properties of Aldehydes and Ketones I Spectra of Aldehydes and Ketones Aldehydes and ketones have strong carbonyl stretching frequencies in the cm -1 region Vibrations of the - bond in an aldehyde gives two weak but characteristic bands at and cm -1 onjugation shifts the I frequency about 40 cm -1 lower because the carbonyl has less double bond character Single bonds stretch more easily than double bonds 16

17 17

18 NM Spectra of Aldehydes and Ketones 13 NM Spectra Aldehyde and ketone carbonyl carbons give characteristic signals at δ ppm 1 NM Spectra Aldehyde protons give sharp signals at δ 9-12 ppm Protons on the α carbon of aldehydes or ketones generally appear at δ

19 19

20 Preparation of Aldehydes Aldehydes by xidation of 1 o Alcohols Primary alcohols are oxidized to aldehydes by P 20

21 xidation with Pyridinium hlorochromate. r 3 l N 2 l 2 aldehydes do not oxidize further P xidation 21

22 xidation with hromic xide and Pyridine r 3. N 2 l 2 aldehydes do not oxidize further 22

23 Preparation of Ketones Ketones from Alkenes, Alkynes,Arenes, and 2 o Alcohols 1) Ketones can be made from alkenes by ozonolysis 23

24 2) Aromatic ketones can be made by Friedel-rafts Acylation. 3) Ketones can be made from 2 o alcohols by oxidation 24

25 4) Ketones from Alkynes Markovnikov hydration of an alkyne initially yields a vinyl alcohol (enol) which then rearranges rapidly to a ketone (keto) 25

26 Addition eactions of Aldehydes and ketones.. : δ+ δ - nucleophilic at oxygen electrophiles add here.. - : : + + or E + 26 Nu: nucleophiles attack here electrophilic at carbon

27 Nucleophilic Addition to arbonyl Basic or Neutral Solution.. : :.. _ : - + :Nu + 2 slow fast :.. _ : Nu :.. an alkoxide ion Nu or on adding acid Nu 27 Good nucleophiles and strong bases (usually charged) BASI SLUTIN

28 Nucleophilic Addition to arbonyl.. : Acid atalyzed + + fast + : more reactive to addition than the unprotonated precursor :Nu slow.. : Nu (+) 28 Acid catalysis speeds the rate of addition of weak nucleophiles and weak bases (usually uncharged). p 5-6 AIDI SLUTIN stronger acid protonates the nucleophile

29 elative eactivity: Aldehydes versus Ketones Aldehydes are generally more reactive than ketones a ketone an aldehyde formaldehyde Due to Increasing reactivity 1)The tetrahedral carbon resulting from addition to an aldehyde is less sterically hindered than the tetrahedral carbon resulting from addition to a ketone 29

30 sp2 less hindered sp3, more hindered ) Aldehyde carbonyl groups are more electron deficient because they have only one electron-donating group attached to the carbonyl carbon 30

31 A more hindered ketone is less reactive than an aldehyde or a less hindered ketone an ethyl ketone a methyl ketone an aldehyde Increasing reactivity 31

32 1) eaction with Water ' aldehyde or ketone favored ' a hydrate most hydrates revert to an aldehyde or ketone as soon as they form hydrates are unstable and cannot be isolated in most cases 32 ' + 2 '

33 AID ATALYSIS EALL +.. : : + :.. + Acid catalysis enhances the reactivity of the carbonyl group - nucleophilic addition proceeds more easily. :Nu weak nucleophiles can react 33

34 WATE ADDS T TE ABNYL GUP F ALDEYDES AND KETNES T FM YDATES + catalyzed by a trace of acid : : : : : + a hydrate for most compounds the equilibrium favors the starting materials and you cannot isolate the hydrate MIEVESIBILITY: In a reaction where all steps are reversible, the steps in the reverse reaction are the same as those in the forward reaction, reversed!

35 SME STABLE YDATES these also indicate that hydrates are possible δ δ 35 δ+ chloral δ + 2 formaldehyde chloral hydrate + formaldehyde hydrate (formaline)

36 2) Addition of Alcohols TW MLES F ALL WILL ADD addition of one mole + hemiacetal addition of second mole + 36 an acetal

37 AETALS AND EMIAETALS aldehyde hemiacetal acetal ketone (hemiketal) (ketal) 37

38 Examples a hemiacetal an acetal hemiketal ketal 38

39 + Mechanism : : : AID ATALYZED FMATIN F A EMIAETAL Normally the starting material is favored - but a second molecule of alcohol can react if in excess (next slide) first addition hemiacetal.. :.... : :

40 FMATIN F TE AETAL ( from the hemiacetal ) :.. :.. hemiacetal.. + : + + : :.. :.. acetal.. :.. S N 1.. :.... remove :.. + :.. second addition + : : esonance stabilized carbocation

41 STABILITY F AETALS AND EMIAETALS Most hemiacetals are not stable, except for those of sugars (see later). Acetals are not stable in aqueous acid, but they are stable to aqueous base. AQUEUS AID 2 S AQUEUS BASE Na 2 no reaction 41

42 42 YLI AETALS

43 Formation of 2,2-Dimethoxypropane TIS IS A NN-YLI AETAL dry acid remove

44 YLI AETALS AND KETALS yclic acetals can be formed if a bifunctional alcohol is used. 1,2-ethanediol /benzene 3 acetophenone

45 USE F A YLI AETAL AS A PTETING GUP Br Br 3 + MgBr The Grignard eaction Takes Place in Basic Solution - The Acetal is Stable Acetals ydrolyze in Acidic Solution MgBr 45

46 yclization of Monosaccharides 1 only sugars seem to make stable hemiacetals 1 a hemiacetal : : glucose glucopyranose

47 Stable hemiacetals : : : a hemiacetal carbon has and 47

48 3) Addition of hydrogen yanide a cyanohydrin 48

49 SYNTESIS F AN α-ydxyaid 49 acetophenone 3 NaN N Aldehydes also work unless they are benzaldehydes, which give a different reaction (benzoin condensation). 3 N 1) Na/ 2 / 2) a cyanohydrin

50 4) eactions with Grignard eagents Nucleophilic attack of Grignard reagents at carbonyl carbons is the most important reaction of Grignard reagents eaction of Grignard reagents with aldehydes and ketones yields a new carbon-carbon bond and an alcohol 50

51 51 Mechanism

52 Alcohols from Grignard eagents Aldehydes and ketones react with Grignard reagents to yield different classes of alcohols depending on the starting carbonyl compound 52

53 53 EXamples

54 54

55 Planning a Grignard Synthesis Example : Synthesis of 3-phenyl-3-pentanol 55

56 Solved Problem: Synthesize the following compound using an alcohol of not more than 4 carbons as the only organic starting material 56

57 Summary of Addition eactions of Aldehydes and ketones 1. Addition of 2 ydrates 2. Addition of alcohols hemiacetal and acetals. 3. Addition of cyanide cyanohydrin 4. Addition of Grignard reagents alcohols. 57

58 58 Addition- Elimination eactions of Aldehydes and Ketones Some reagents undergo addition reactions to aldehydes and ketones followed by elimination of water. Aldehyde or Ketone + Nu addition Nu elimination _ 2 Nu

59 (Memorization ) eactions with = : Primary amines yield imines Secondary amines yield enamines Tertiary amines do not react N AMINES: N N 59 primary secondary tertiary

60 1) eaction with ammonia and primary amines + N 2 + N 2-2 N An imine N 3 N N + 3 N 60

61 Mechanism of Imine Formation Step1: addition + 'N 2 fast - N 2 ' + fast ' N Step2: elimination 'N + fast + 2 'N - 2 slow N ' fast N' 61

62 Formation of Simple Imines overall result remove N N + 2 an imine 62 These reactions do not favor the formation of the imine unless: - the product is insoluble (crystallizes or precipitates) or - water is removed to drive the equilibrium

63 ydrolysis of Simple Imines EVESAL In an excess of aqueous acid, simple imines hydrolyze back to the aldehyde or ketone and the amine from which they were orginally formed.. N N an imine Imines that are not soluble, however, are difficult to hydrolyze. 63

64 YSTALLINE IMINES shown below There are some special amines that yield insoluble products (imines) that are easy to crystallize.... :N 2 hydroxylamine 2 N NN 2 semicarbazine.. -N-N 2 various hydrazine compounds 2 N N 2.. NN 2 2,4-dinitrophenylhydrazine 64

65 Formation of ximes aldehyde or ketone N N + 2 hydroxylamine an oxime (usually crystallizes) 2 N + + N an oxime 65

66 Formation of ydrazones aldehyde or ketone N N N N + 2 a hydrazine a hydrazone + 2 NN + NN 66 Phenylhydrazine Phenylhydrazone

67 2,4-Dinitrophenylhydrazones N 2 2,4-dinitrophenylhydrazine N N N 2 2,4-dinitrophenylhydrazine aldehyde or ketone 67 insoluble red, orange or yellow precipitate forms N 2 N N N ,4-dinitrophenylhydrazone a 2,4-DNP (precipitates)

68 Formation of Semicarbazones semicarbazide N N N 2 semicarbazide aldehyde or ketone N N N a semicarbazone 68 (usually crystallizes)

69 SENDAY AMINES ENAMINES 69

70 Formation of Enamines secondary amine β-hydrogen is required N N 2 + N 2 An iminium ion 70 an enamine generally removed by azeotropic distillation

71 1) : : Enamine Formation MEANISM : + 2) +.. slow : N + N - N : 71 continued.

72 Enamine Formation (cont) MEANISM 3) ) 72 N + : : : N N + - N : enamine N + water must be removed to force the equilibrium

73 Examples + N 2 + N + N + N 73

74 74 WITTIG EATIN

75 Ylide A compound or intermediate with both a positive and a negative charge on adjacent atoms X BND Y Betaine or Zwitterion 75 A compound or intermediate with both a positive and a negative charge, not on adjacent atoms, but in different parts of the molecule. - MLEULE : X Y +

76 Preparation of a Phosphorous Ylide ( WITTIG EAGENT ) a phosphonium ion 1 Ph.. P 2 X Ph Ph + ( 6 5 ) 3 P ( Ph = 6 5 ) Triphenylphosphine 1 ( 6 5 ) 3 P 2 : S N 2 heat 1 + ( 6 5 ) 3 P 2 X _ -Li ether strong base ( 6 5 ) 3 P an ylide

77 The Wittig eaction MEANISM ( 6 5 ) 3 P 2 4 ylide Aldehyde or ketone betaine : : P(.. _ 6 5 ) P( ) synthesis of an alkene 77 Triphenylphosphine oxide :.. P( 6 5 ) 3 oxaphosphetane (UNSTABLE)

78 examples + ( 6 5 ) 3 P ( 6 5 ) 3 P= + ( 6 5 ) 3 P 78 + ( 6 5 ) 3 P=

79 SYNTESIS F AN ALKENE - WITTIG EATIN Br :P( 6 5 ) 3 + ( 6 5 ) 3 P ( 6 5 ) 3 P 2 3 ylide - : 3 Na 79

80 ANTE WITTIG ALKENE SYNTESIS 2 Br :P( 6 5 ) 3 + P( 6 5 ) 3 PhLi Br : P( ) 3 + triphenylphosphine oxide (insoluble) P( ) ylide Br

81 EDUTIN F ALDEYDES AND KETNES 81

82 EDUTIN F ALDEYDES AND KETNES ALL, YDABN, AMINE N 2 ' or 2 or Aldehyde or ketone An alcohol A hydrocarbon An amine 82

83 eduction by ydrogenation Aldehyde or ketone + 2 /pt alcohol / Pt o a 1 alcohol + 2 Pt o a 2 alcohol 83

84 If both = and carbonyl present 1. At low T & P = is hydrogenated but not = Ni 25 o At high T & P both = and = are hydrogenated Ni heat, p

85 eduction with Metal ydride 85 Na + - B sodium borohydride YDIDE EAGENTS.... _ : : : : _ NaB 4 Li Al LiAl lithium aluminum hydride 3 + simplified mechanism

86 SDIUM BYDIDE IS SELETIVE NaB 4 only reduces aldehydes and ketones only aldehyde 1 2 NaB4 3 + primary alcohol or ketone secondary alcohol 1 NaB The double bond and the ester are not touched. 86 Me Me

87 Sodium Borohydride eduction of Aldehydes and Ketones aldehyde and ketones + Na - B 3 NaB workup - step B 3 alcohol 87

88 Sodium Borohydride eduction of Norcamphor exo attack 1 NaB bicyclo[2.2.1]heptan-2-one (norcamphor) endo alcohol (86%) exo alcohol (14%) 88

89 eduction with LiAl 4 LiAl 4 reduces any carbonyl but not = 1) LiAl 4 2) +, 2 3 1) LiAl 4 2) +, Aldehyde and ester carbonyl are reduced to primary alcohol but not =.

90 eduction to hydrocarbon TW METDS 1) lemmensen eduction Zn(g) + conc. l strong acid conditions 2) Wolff-Kishner eduction N 2 N 2 + K strong base conditions 90

91 Examples lemmensen eduction Zn/g l 2 3 Wolf-Kishner eduction NN 2 K N 2 N 2, + 91

92 eductive Amination Aldehydes and ketones react with ammonia, primary or secondary amines to yield imines or iminium ions The imines and iminium ions can then be reduced to new primary, secondary or tertiary amines, respectively 92

93 93 Mechanism

94 94 Examples

95 eductive amination is a good method for preparation of amines 95

96 96 xidation of Aldehydes and Ketones Ketones are not easily oxidized KMn no reaction a ketone Aldehydes are easily oxidized to carboxylic acids using KMn 4 or 2 r an aldehyde KMn a carboxylic acid

97 Aldehydes form hydrates in water An aldehyde hydrate formation is the reason that aldehyde are easily oxidize to carboxylic acid. 97

98 Tollens eagent Aldehyde are oxidized by very mild oxidizing agents e.g. Ag + Ag(N 3 ) Tollens reagent Ag mirror 98

99 The Acidity of the α ydrogens of arbonyl ompounds ydrogens on carbons α to carbonyls are unusually acidic. 99

100 Why α hydrogen is acidic Stong base is neede eg. Na, or NaN 2 100

101 pka of Ethylacetoacetate is 11 α to two = groups Three resonance structures stabilize the anion - 101

102 Keto-Enol Tautomerism K keto enol For most ketones, the keto form predominates in the equilibrium 102

103 Enol Percentages are Low in Most rdinary Ketones 4.1 x 10-4 % < 2 x 10-4 % x 10-3 %

104 β-dicarbonyl compounds exist primarily in the enol form The enol is more stable because it has a conjugated pi system and because of stabilization of the enol through hydrogen bonding 104

105 α -alogenation of Ketones Ketones can be halogenated at the α position in the presence of acid or base and X Br Br + Br 2 + Br α bromocyclohexanone 105

106 Base-promoted halogenation occurs via an enolate Mechanism 106

107 Acid-catalyzed halogenation proceeds via the enol Mechanism 107

108 aloform eaction eaction of methyl ketones with X 2 in the presence of base results in multiple halogenation at the methyl carbon 108

109 109

110 Methyl ketones react with X 2 in aqueous hydroxide a carboxylate anion and a haloform (X 3 ) 110

111 Iodoform eaction Na I I Na 3 yellow precipitate Na.. 2 I I Na 2 - : I I I 111 I 2 2 I 2 I 2 more..- :.. I I I good leaving group

112 Syntheses Guidlines Think backward Think of functional groups inter conversions. If the carbon chain increases think of Grignard or Wittig reactions 112

113 Examples? l 113

114 Synthesis? l 2, + 2 r l - S N 2

115 Another synthetic problem 2 2 3? P( 6 5 )

116 Solution 2 2 3? 3 2 P( 6 5 ) , Ni 116

117 Synthetic problems 1)? 2 2)? l N )?