Carbonyl Chemistry V + C O C. Chemistry /30/02

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1 arbonyl hemistry V Ō - +

2 Keto-enol enol Tautomerism H 3 H 3 Ketone H H R 2 H R' H H 3 H 2 H Enol H

3 Acid atalyzed α Halogenation R 2 R' + X 2 H + R 2 R' + HX H X X 2 can be l 2, Br 2, or I 2. Substitution is specific for replacement of α hydrogen. Nota free-radical reaction.

4 Mechanism of α Halogenation Two steps: first step is slow conversion of aldehyde or ketone to the corresponding enol; is ratedetermining second step is the fast reaction of the enol with halogen; far faster than the first stage

5 Mechanism of α Halogenation RH 2 R' H + H X 2 slow RH R' enol fast Enol is the key intermediate RHR' X

6 Acid catalyzed a-halogenationa H H vs. I 2 I H 3 HI, H 2 H 3

7 Base catalyzed α-halogenation Base-promoted α-halogenation Step 1: formation of an enolate anion H H H - H H 2 + H 2 H 2

8 Base catalyzed α-halogenation Base-promoted α-halogenation Step 2: nucleophilic attack of the enolate anion on halogen H 2 Br Br H 2 Br Br -

9 α-halogenation So there are major differences between acid- catalyzed and base-promoted α-halogenation 1. Acid catalysis gives the most substituted product 2. The rate of acid-catalyzed introduction of a second halogen is slower than the first introduction of the electronegative halogen on the α-carbon decreases the basicity of the carbonyl oxygen toward protonation

10 α-halogenation In base catalyzed α-halogenation, each successive halogenation is more rapid than the previous one the introduction of the electronegative halogen on the α-carbon increases the acidity of the remaining α-hydrogens and, thus, each successive α-hydrogen is removed more rapidly than the previous one

11 Relative Rates Rule H 3 H - H 1 2 l + 1 l 2 SLW FASTER?? l 3 FASTER STILL Hl 2

12 The Haloform Reaction Under basic conditions, halogenation of a methyl ketone often leads to carbon-carbon bond cleavage. This is called the haloform reaction because chloroform, bromoform, or iodoform is one of the products.

13 Haloform Reaction Iodoform Reaction A qualitative test for methyl ketones A decent way to synthesize carboxylic acids R H 3 3I 2 NaH R I I I H - R - + HI 3 Iodoform

14 First stage is substitution of all available α hydrogens by halogen RH 3 RX 3 X 2, H X 2, H RH 2 X X 2, H RHX 2

15 Formation of the trihalomethyl ketone is followed by its hydroxide-induced induced cleavage H + R X 3 R X 3 R + HX 3 R H H + X 3

16 Example (H 3 ) 3 H 3 Br 2, NaH,, H 2 (H 3 ) 3 Na H + + HBr 3 (H 3 ) 3 H

17 Haloform Reaction Summary of Iodoform Reaction R H 3 3I 2 NaH R I I I H - R - + HI 3 Iodoform A qualitative test for methyl ketones A decent way to synthesize carboxylic acids

18 arboxylic Acids R H R + H + - hapter 17 R -

19 Nomenclature - IUPA IUPA names: drop the -e from the parent alkane and add the suffix -oic acid If the compound contains a carbon-carbon double bond, change the infix -an- to -en- H 2 =H 2 H Propenoic acid (Acrylic acid) 6 H 5 H H 2 H trans-3-phenylpropenoic acid (innamic acid) H 3 H H 2 H trans-2-butenoic acid (rotonic acid)

20 Nomenclature-ommon When common names are used, the letters α, β, γ, δ, etc. are often used to locate substituents HH 2 H 2 H 2 2 H 4-Hydroxybutanoic acid (γ-hydroxybutyric acid) δ γ β α -----H NH 2 H 3 H 2 H 2-Aminopropanoic acid (α-aminopropionic acid; Alanine)

21 Naming the Salts To name the salt of the carboxylic acid, name the cation followed by the name of the anion (two words). The anion is named by removing -oic acid and adding ate Benzoic acid Butyric acid Sodium benzoate Ammonium butyrate

22 Boiling Points H bp (1 atm) H Intermolecular forces, especially hydrogen bonding, are stronger in carboxylic acids than in other compounds of similar shape and molecular weight

23 Physical Properties In the liquid and solid states, carboxylic acids are associated by hydrogen bonding into dimeric structures δ- δ+ δ+ δ- H 3 H H H 3

24 Acidity arboxylic acids are weak acids The pk a of typical aliphatic and aromatic carboxylic acids falls within the range 4 to 5 The greater acidity of carboxylic acids relative to alcohols, both of which have oxyanions conjugate bases is because: R H R + H + R - - the carboxylate anion is stabilized by resonance

25 Infrared Spectrum of 4-Phenylbutanoic4 acid 6 H 5 H 2 H 2 H 2 2 H H and H stretch = monosubstituted benzene Wave number, cm -1

26 1 H NMR of arboxylic acids The acidic proton in the H- croup of a carboxylic acid is normally the least shielded of all protons in a 1 H nmr spectrum: (d ppm; ; broad) it moves and it is subject to exchange

27 H 2 H 2 H 2 H hemical shift (δ,( ppm)

28 13 NMR of arboxylic acids The arbonyl carbon on the carboxylic acid group is at low field (δ( ppm), but not quite as deshielded as the carbonyl carbon of an aldehyde or ketone (δ( ppm).

29 Mass Spectrometry The McLafferty rearrangement gives a characteristic peak at m/z = 60 H 2 H + McLafferty rearrangement H 2 H 2 H H 2 H 2 + H H 2 H + m/z 60

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31 Acidity Electron-withdrawing substituents near the carboxyl group increase acidity through their inductive effect H I Br l F H 2 2 H H 2 2 H H 2 2 H H 2 2 H H 2 2 H Acid Strength

32 Acidity Substitution by multiple electronwithdrawing groups further increases acidity H 3 2 H H 2 l 2 H Hl 2 2 H l 3 2 H Acetic hloroacetic Dichloroacetic Trichloroacetic pk : a Acid Strength

33 Acidity The inductive effect of an electronwithdrawing substituent falls off rapidly with its distance from the carboxyl group l l l H 2 H 2 H 2 2 H H 3 HH 2 2 H H 3 H 2 H 2 H 4-hlorobutanoic 3-hlorobutanoic 2-hlorobutanoic pk a : Acid Strength

34 Reactions of Acids Reduction Decarboxylation Esterification Formation of Acid Halides

35 Reduction The carboxyl groups is one of the organic functional groups most resistant to reduction it is not affected by catalytic hydrogenation under conditions that easily reduce aldehydes and ketones to alcohols, and reduce alkenes and alkynes to alkanes it is not reduced by NaBH 4

36 Reduction by LiAlH 4 Lithium aluminum hydride reduces a carboxyl group to a 1 alcohol reduction is carried out in diethyl ether, THF, or other nonreactive, aprotic solvent H 1. LiAlH 4, ether 2. H 2 H 2 H + LiH + Al(H) 3

37 Selective Reduction Using the less reactive NaBH 4, it is possible to reduce the carbonyl group of an aldehyde or ketone without affecting a carboxyl group H 2 H 2 H 2 H 1.NaBH 4 2. H 2 H HH 2 H 2 H 2 H

38 Fischer Esterification The key intermediate in Fischer esterification is the tetrahedral addition intermediate formed by addition of RH to the = group R H H 3 tetrahedral carbonyl addition intermediate R H + HH 3 H H + H + R H 3 + HH