Lecture 19 arboxylic Acids R R - + + R - March 29, 2018
Review: Selectivity in Reduction LiAl 4 reduces any and all carbonyl compounds to the corresponding alcohols NaB 4 only reduces aldehydes and ketone
atalytic Reduction atalytic reductions are generally carried out from 25 to 100 and from 1 to 5 atm 2 arbon-carbon double bonds can be selectively reduced using Rhodium catalysts 2 /Rh NaB 4 Me
ydrogenolysis of benzylic carbonyls Palladium catalysis of hydrogenation reduces only benzylic - bonds to methylene groups. Benzyl ethers, aldehydes and alcohols are also reduced to the corresponding methylene group 2, Pd/ 2, Pd/
lemmensen Reduction Refluxing an aldehyde or ketone with amalgamated zinc in concentrated l converts the carbonyl group to a methylene group Limitations?? ( 2 ) 5 3 Zn(g), l 2 (2 ) 5 3
Wolff-Kishner Reduction If aldehydes or ketones are refluxed with hydrazine and K in a high-boiling solvent, the reaction converts carbonyls into methylenes. Diethyleneglycol K, 2 NN 2, D
hromic Acid xidations r 3 K 2 r 2 4 K 2 r 2 7 exavalent chromium compounds (including chromium trioxide, chromic acids, chromates, chlorochromates) are toxic and carcinogenic.
xidation at Benzylic Positions KMn4 in Base also works
Selective hromate xidations hromic acid and heat xidizes benzylic positions bearing at least one hydrogen to acids Jones Reagent ( 2 r 4 in acetone) takes primary alcohols to acids and secondary alcohols to ketones The acetone keeps the reaction cool. Jones oxidation does not oxidize benzylic positions even with a hydrogen. P (pyridinium chlorochromate) is weaker yet, it only oxidizes primary alcohols to aldehydes (!) and seconday alcohols to ketones.
The Jones xidation - Examples 2 S 4 2 r 4, Acetone 2 S 4 2 r4,acetone 3 3 2 r 4, Aceto n e
P xidations 5 5 N + l + r 3 [ 5 5 N][r 3 l]
Selectivity!!? 4 3-4 -2 0 +2 +4 xidation Reduction
Selective xidation Reactions Jones Reagent ( 2 r 4 in acetone) takes primary alcohols to acids and secondary alcohols to ketones The Tollen s Test Ag(N 3 ) 2 the silver mirror reaction is a qualitative test for aldehydes and an efficient but expensive way to make acids form aldehydes
Tollens Test
Examples 2 r 4, Acetone 2 S 4 2 r 4, Acetone 2 S 4 2 r 4, Acetone 3 3 3 Ag(N 3 ) 2 3 + Ag 0
k let s do some synthesis? 3
k more synthesis From benzene, any thing with less than 3 carbons, and any other reagents that do not become part of the structure. 3 3 3 3 3
Keto-enol Tautomerism + 3 3 3 Ketone Enol 2 3 3 Ketone + 3 3 + 2 Enol +
Deuterium Exchange Deuterium exchange at an -carbon may be catalyzed by either acid or base D + 3 3 + 6 D 2 D 3 D 3 + 6 D Acetone or D - Acetone-d 6
Keto-Enol Tautomerism Keto-enol equilibria for simple aldehydes and ketones lie far toward the keto form Keto form 3 3 3 Enol form 2 = % Enol at Equilibrium 6 x 10-5 3 = 2 6 x 10-7 4 x 10-5
Keto-Enol Tautomerism For certain types of molecules, however, the enol is the major form present at equilibrium for -diketones, the enol is stabilized by conjugation of the pi system of the carbon-carbon double bond and the carbonyl group 1,3-yclohexanedione
Keto-enol tautomerism in -diketones and -ketoesters pen-chain -diketones are further stabilized by intramolecular hydrogen bonding 3 -- 2 -- 3 20% hydrogen bonding 3 2,4-Pentanedione (Acetylacetone) d- d+ 80% 3
Tautomerism 10 9 8 7 3 3 6 3 3 5 4 3 2 1 0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
Acidity of protons to carbonyls The anion is stabilized by resonance the better the stabilization, the more acidic the proton Acidity of a protons on normal aldehydes and ketones is about that of alcohols and less than water pka ~ 18-20 Some are far more acidic, i.e. -dicarbonyl compounds that have quite low pka s
Enolate anions ydrogens to carbonyls are acidic 3-3 - 2 + 2 Resonance stabilized enolate anion - 3 2
3 2 F l 4.75 3.45-9.0!! 10 pka of some acids and some protons 3 3 2 3 5.0 16 9 A span of 59 powers of 10!!! 3 3 3 3 20 50
-alogenation -alogenation: aldehydes and ketones with at least one -hydrogen react at an - carbon with Br 2 and l 2 and the reaction is catalyzed by both acid and base 3 Acetophenone + Br 2 3 2 2 Br + Br
-alogenation Acid-catalyzed -halogenation Step 1: acid-catalyzed enolization R'---R R - slow R' R Step 2: Nucleophilic attack of the enol on halogen R - R' R R + Br-Br fast R' Br R R + -Br
-alogenation Base-promoted -halogenation Step 1: formation of an enolate anion - 2 + 2 2
Base catalyzed -alogenation Base-promoted -halogenation Step 2: nucleophilic attack of the enolate anion on halogen 2 Br Br 2 Br Br -
-alogenation In base catalyzed -halogenation, each successive halogenation is more rapid than the previous one the introduction of the electronegative halogen on the -carbon increases the acidity of the remaining -hydrogens and, thus, each successive -hydrogen is removed more rapidly than the previous one
aloform Reaction Iodoform Reaction A qualitative test for methyl ketones A decent way to synthesize carboxylic acids R 3 3 I 2 Na R I I I - R - + I 3 Iodoform
-alogenation There are major differences between acid-catalyzed and base-promoted -halogenation Acid catalysis gives the most substituted product The rate of acid-catalyzed introduction of a second halogen is slower than the first introduction of the electronegative halogen on the -carbon decreases the basicity of the carbonyl oxygen toward protonation so monosubstitution is possible. base promoted halogenation goes all the way because the product is more acidic than the starting material