APTE 13 ALDEYDES AND KETNES 1
Aldehyde STUTUE =, alkyl, aryl Ketone ' and ' = alkyl or aryl and ' cannot be hydrogen! 2
3 NMENLATUE
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
EXAMPLES 3 2 2 3 2-Pentanone 3 2 2 3 2 5 3 4-Ethyl-3-hexanone
2,4-pentanedione 3 3 2 3 3 3-Isopropylcyclopentanone or 3-(1-Methylethyl)cyclopentanone 6
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
Example of ommon Names 3 2 2 3 Methyl propyl ketone 3 3 2 2 Diethyl ketone 8
3 3 dimethyl ketone acetone A common laboratory solvent and cleaning agent SPEIAL ASES diphenyl ketone benzophenone 3 methyl phenyl ketone 9 acetophenone
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
EXAMPLES 2 2 3 2 aldehyde group is always carbon 1 pentanal l 4 3 3 2 1 3 2-chloro-3-methylbutanal 11
ommon Names of the Aldehydes 3 3 2 Formaldehyde Acetaldehyde Propionaldehyde 1 2 3 3 2 3 2 2 Butyraldehyde Valeraldehyde 4 5 3 2 2 2 2 aproaldehyde 12 6
SPEIAL ASES formaldehyde 3 benzaldehyde acetaldehyde 13
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 )
Examples 15 1,4-cyclohexanedione 3-hydroxypentanal 2-cyclopentenone 3-phenylpropanal β phenylproionaldehyde
Spectral properties of Aldehydes and Ketones I Spectra of Aldehydes and Ketones Aldehydes and ketones have strong carbonyl stretching frequencies in the 1665-1780 cm -1 region Vibrations of the - bond in an aldehyde gives two weak but characteristic bands at 2700-2775 and 2820-2900 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
NM Spectra of Aldehydes and Ketones 13 NM Spectra Aldehyde and ketone carbonyl carbons give characteristic signals at δ 180-220 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 2.0-2.4 18
19
Preparation of Aldehydes Aldehydes by xidation of 1 o Alcohols Primary alcohols are oxidized to aldehydes by P 20
xidation with Pyridinium hlorochromate. r 3 l N 2 l 2 aldehydes do not oxidize further P xidation 21
xidation with hromic xide and Pyridine r 3. N 2 l 2 aldehydes do not oxidize further 22
Preparation of Ketones Ketones from Alkenes, Alkynes,Arenes, and 2 o Alcohols 1) Ketones can be made from alkenes by ozonolysis 23
2) Aromatic ketones can be made by Friedel-rafts Acylation. 3) Ketones can be made from 2 o alcohols by oxidation 24
4) Ketones from Alkynes Markovnikov hydration of an alkyne initially yields a vinyl alcohol (enol) which then rearranges rapidly to a ketone (keto) 25
Addition eactions of Aldehydes and ketones.. : δ+ δ - nucleophilic at oxygen electrophiles add here.. - : : + + or E + 26 Nu: nucleophiles attack here electrophilic at carbon
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
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
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
sp2 less hindered sp3, more hindered 3 2 + 2 3 2) Aldehyde carbonyl groups are more electron deficient because they have only one electron-donating group attached to the carbonyl carbon 30
A more hindered ketone is less reactive than an aldehyde or a less hindered ketone 3 2 2 2 3 3 2 2 3 3 2 2 an ethyl ketone a methyl ketone an aldehyde Increasing reactivity 31
1) eaction with Water ' + 2 + 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 '
AID ATALYSIS EALL +.. : : + :.. + Acid catalysis enhances the reactivity of the carbonyl group - nucleophilic addition proceeds more easily. :Nu weak nucleophiles can react 33
WATE ADDS T TE ABNYL GUP F ALDEYDES AND KETNES T FM YDATES + catalyzed by a trace of acid.. +.... : : : :.......... : + a hydrate.... + 34 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!
SME STABLE YDATES these also indicate that hydrates are possible δ δ 35 δ+ chloral δ + 2 formaldehyde chloral hydrate + formaldehyde hydrate (formaline)
2) Addition of Alcohols TW MLES F ALL WILL ADD addition of one mole + hemiacetal addition of second mole + 36 an acetal
AETALS AND EMIAETALS aldehyde hemiacetal acetal ketone (hemiketal) (ketal) 37
Examples 3 3 2 + 2 3 3 a hemiacetal 3 2 + 2 3 3 2 3 an acetal 3 + 3 3 + 3 3 hemiketal ketal 38
+ 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) 39.... first addition hemiacetal.. :.... : :.. + +.. +
FMATIN F TE AETAL ( from the hemiacetal ) 40.. + :.. :.. hemiacetal.. + : + + : :.. :.. acetal.. :.. S N 1.. :.... remove :.. + :.. second addition + : : esonance stabilized carbocation
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 4 2 + AQUEUS BASE Na 2 no reaction 41
42 YLI AETALS
Formation of 2,2-Dimethoxypropane TIS IS A NN-YLI AETAL 3 3 + 2 3 dry acid remove 2 3 3 3 3 43
YLI AETALS AND KETALS yclic acetals can be formed if a bifunctional alcohol is used. 1,2-ethanediol 2 2 2 2 + /benzene 3 acetophenone 2 3 + + + 2 44
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
yclization of Monosaccharides 1 only sugars seem to make stable hemiacetals 1 a hemiacetal 2 2 3 3 : : 4 4 2.... 5 5 6 6 2 46 glucose glucopyranose
Stable hemiacetals 4 5 3 4 3.. : : : 2 1 2 1 6 5 a hemiacetal carbon has and 47
3) Addition of hydrogen yanide a cyanohydrin 48
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) 3 + 3 a cyanohydrin
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 Mechanism
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 EXamples
54
Planning a Grignard Synthesis Example : Synthesis of 3-phenyl-3-pentanol 55
Solved Problem: Synthesize the following compound using an alcohol of not more than 4 carbons as the only organic starting material 56
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 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
(Memorization ) eactions with = : Primary amines yield imines Secondary amines yield enamines Tertiary amines do not react N AMINES:...... N N 59 primary secondary tertiary
1) eaction with ammonia and primary amines + N 2 + N 2-2 N An imine + + 2 N 3 N 3 3 + 2 N + 3 N 60
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
Formation of Simple Imines overall result remove.. + + 2 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
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 3 + + 2 + 2.. N an imine Imines that are not soluble, however, are difficult to hydrolyze. 63
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
Formation of ximes aldehyde or ketone.. + 2 N N + 2 hydroxylamine an oxime (usually crystallizes) 2 N + + N an oxime 65
Formation of ydrazones aldehyde or ketone.. + 2 N N N N + 2 a hydrazine a hydrazone + 2 NN + NN 66 Phenylhydrazine Phenylhydrazone
2,4-Dinitrophenylhydrazones N 2 2,4-dinitrophenylhydrazine +.. 2 N N N 2 2,4-dinitrophenylhydrazine aldehyde or ketone 67 insoluble red, orange or yellow precipitate forms N 2 N N N 2 + 2 2,4-dinitrophenylhydrazone a 2,4-DNP (precipitates)
Formation of Semicarbazones semicarbazide +.. 2 N N N 2 semicarbazide aldehyde or ketone N N N 2 + 2 a semicarbazone 68 (usually crystallizes)
SENDAY AMINES ENAMINES 69
Formation of Enamines secondary amine β-hydrogen is required.. + 2 N + + 2 + - 2 N 2 + N 2 An iminium ion 70 an enamine generally removed by azeotropic distillation
1) : : Enamine Formation -- + + + MEANISM.... + : + 2) +.. slow -- +.. : +.. 2.. N + N - N : 71 continued.
Enamine Formation (cont) MEANISM 3) +.. 2 + 4) 72 N + : : : N N + - N : enamine + + 2 2 + + 3 + N + water must be removed to force the equilibrium
Examples + N 2 + N + N + N 73
74 WITTIG EATIN
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 +
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 1 2 76
The Wittig eaction MEANISM 1 + + -.. 1 3 2 3 4 ( 6 5 ) 3 P 2 4 ylide Aldehyde or ketone betaine : : P(.. _ 6 5 ) 3 + 1 3 P(6 1 3 + 5 )3 2 4 2 4 synthesis of an alkene 77 Triphenylphosphine oxide :.. P( 6 5 ) 3 oxaphosphetane (UNSTABLE)
examples + ( 6 5 ) 3 P 3 3 + ( 6 5 ) 3 P= + ( 6 5 ) 3 P 78 + ( 6 5 ) 3 P=
SYNTESIS F AN ALKENE - WITTIG EATIN 3 3 2 3 3 3 Br 2 3 3 3 :P( 6 5 ) 3 + ( 6 5 ) 3 P 2 3 + ( 6 5 ) 3 P 2 3 ylide - : 3 Na 79
ANTE WITTIG ALKENE SYNTESIS 2 Br :P( 6 5 ) 3 + P( 6 5 ) 3 PhLi Br - 80 - +.. : P(.. 6 5 ) 3 + triphenylphosphine oxide (insoluble) P(.. 6 5 ) 3 - + ylide Br
EDUTIN F ALDEYDES AND KETNES 81
EDUTIN F ALDEYDES AND KETNES ALL, YDABN, AMINE N 2 ' or 2 or Aldehyde or ketone An alcohol A hydrocarbon An amine 82
eduction by ydrogenation Aldehyde or ketone + 2 /pt alcohol 3 2 2 / Pt 3 2 2 o a 1 alcohol + 2 Pt o a 2 alcohol 83
If both = and carbonyl present 1. At low T & P = is hydrogenated but not =. 3 2 + 2 Ni 25 o 3 2 2 2 2. At high T & P both = and = are hydrogenated 84 + 2 Ni heat, p
eduction with Metal ydride 85 Na + - B sodium borohydride YDIDE EAGENTS.... _ : : : : _ NaB 4 Li Al LiAl 4 + - lithium aluminum hydride 3 + simplified mechanism
SDIUM BYDIDE IS SELETIVE NaB 4 only reduces aldehydes and ketones only aldehyde 1 2 NaB4 3 + primary alcohol or - 2 - ketone secondary alcohol 1 NaB 4 2 3 + The double bond and the ester are not touched. 86 Me Me
Sodium Borohydride eduction of Aldehydes and Ketones aldehyde and ketones + Na - B 3 NaB 4 3 + workup - step B 3 alcohol 87
Sodium Borohydride eduction of Norcamphor exo attack 1 NaB 4 2 3 + + bicyclo[2.2.1]heptan-2-one (norcamphor) endo alcohol (86%) exo alcohol (14%) 88
eduction with LiAl 4 LiAl 4 reduces any carbonyl but not = 1) LiAl 4 2) +, 2 3 1) LiAl 4 2) +, 2 2 2 89 Aldehyde and ester carbonyl are reduced to primary alcohol but not =.
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
Examples lemmensen eduction Zn/g l 2 3 Wolf-Kishner eduction NN 2 K N 2 N 2, + 91
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 Mechanism
94 Examples
eductive amination is a good method for preparation of amines 95
96 xidation of Aldehydes and Ketones Ketones are not easily oxidized KMn 3 4 3 no reaction a ketone Aldehydes are easily oxidized to carboxylic acids using KMn 4 or 2 r 4. 3 2 2 an aldehyde KMn4 + 3 2 2 a carboxylic acid
Aldehydes form hydrates in water An aldehyde hydrate formation is the reason that aldehyde are easily oxidize to carboxylic acid. 97
Tollens eagent Aldehyde are oxidized by very mild oxidizing agents e.g. Ag + Ag(N 3 ) + + 2 - - + Tollens reagent Ag mirror 98
The Acidity of the α ydrogens of arbonyl ompounds ydrogens on carbons α to carbonyls are unusually acidic. 99
Why α hydrogen is acidic Stong base is neede eg. Na, or NaN 2 100
pka of Ethylacetoacetate is 11 α to two = groups 3 2 2 3 - - Three resonance structures stabilize the anion - 101
Keto-Enol Tautomerism K keto enol For most ketones, the keto form predominates in the equilibrium 102
Enol Percentages are Low in Most rdinary Ketones 4.1 x 10-4 % 3 3 2 3 < 2 x 10-4 % 2 3 2 2 103 2.5 x 10-3 %
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
α -alogenation of Ketones Ketones can be halogenated at the α position in the presence of acid or base and X 2 3 3 + Br 2-3 2 Br + Br 2 + Br α bromocyclohexanone 105
Base-promoted halogenation occurs via an enolate Mechanism 106
Acid-catalyzed halogenation proceeds via the enol Mechanism 107
aloform eaction eaction of methyl ketones with X 2 in the presence of base results in multiple halogenation at the methyl carbon 108
109
Methyl ketones react with X 2 in aqueous hydroxide a carboxylate anion and a haloform (X 3 ) 110
Iodoform eaction Na I I 2 + 3 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
Syntheses Guidlines Think backward Think of functional groups inter conversions. If the carbon chain increases think of Grignard or Wittig reactions 112
Examples? l 113
Synthesis? l 2, + 2 r 4 114 l - S N 2
Another synthetic problem 2 2 3? 2 3 3 2 P( 6 5 ) 3 + 115
Solution 2 2 3? 3 2 P( 6 5 ) 3 2 3 2, Ni 116
Synthetic problems 1)? 2 2)? l N 2 3 117 3)?