Carbonyl Chemistry: Lecture 15 of Chemistry 318N - Prof. Carlton G. Willson, Study notes of Chemistry

Download Carbonyl Chemistry: Lecture 15 of Chemistry 318N - Prof. Carlton G. Willson and more Study notes Chemistry in PDF only on Docsity! 1 Chemistry 318N Lecture 15 March 08, 2007 Carbonyl Chemistry C O R R' •• •• P(C6H5)3 + C A B – •• OC C P(C6H5)3 R R' B A •• •• Chemistry 318N formaldehyde to give primary alcohols (+ 1 C) aldehydes to give secondary alcohols ketones to give tertiary alcohols esters to give tertiary alcohols ( 2 groups identical) CO2 to give acids epoxides to give primary alcohols (+2 C’s) Grignard reagents react with: 2 Chemistry 318N Victor Grignard Shared Nobel Prize with Sabatier in 1912 “student” of Philippe Barbier Chemistry 318N Gilman Reagents
The most common substrate for an organocuparate is a primary alkyl halide, usually an iodide
Secondary and tertiary halides undergo elimination . (CH3)CuLi ICH2(CH2)8CH3 CH3CH2(CH2)8CH3 (C6H5)2LiCu ICH2(CH2)4CH3 C6H5CH2(CH2)4CH3 5 Chemistry 318N Preparation of Ylides The ylid is made in a two step process. The first step is a nucleophilic substitution reaction that Forms a phosphonium salt (C6H5)3P •• + CH A B X (C6H5)3P CH A B + + X– Chemistry 318N Preparation of Ylides (C6H5)3P C A B + •• – H+ base In the second step, the phosphonium salt is treated with a strong base in order to remove a proton from the carbon bonded to phosphorus. (C6H5)3P C A B + H base •• – 6 Chemistry 318N Phosphonium ylides Resonance stabilized R is usually C6H5 (phenyl) Carbon is negatively polarized and nucleophilic (C6H5)3P C + A B •• – (C6H5)3P C A B Chemistry 318N The Wittig Reaction (C6H5)3P C + A B •• – + +C C R R' A B (C6H5)3P O + •• –•• •• C O R R' •• •• “ylide” 7 Chemistry 318N Mechanism C O R R' •• •• P(C6H5)3 + C A B – •• OC C P(C6H5)3 R R' B A •• •• Step 1 Chemistry 318N Mechanism OC C P(C6H5)3 R R' B A •• •• Step 2 P(C6H5)3+ – O •• •••• R'R A B C C + 10 Chemistry 318N Cyanohydrins
The value of cyanohydrins is for the new functional groups into which they can be converted – acid-catalyzed dehydration of the 2° alcohol gives a valuable monomer Propenenitrile (Acrylonitrile) + acid catalyst 2-Hydroxypropanenitrile (Acetaldehyde cyanohydrin) CH3 CHC N OH NCH2 =CHC H2 O Chemistry 318N Cyanohydrins – acid-catalyzed hydrolysis of the cyano group gives an α-hydroxycarboxylic acid acid catalyst Benzaldehyde cyanohydrin (Mandelonitrile) 2-Hydroxy-2-phenyl- ethanoic acid (Mandelic acid) +N OH CHC CHCOH HO O H2 O 11 Chemistry 318N Cyanohydrins – catalytic reduction of the carbon-nitrogen triple bond converts the cyano group gives a 1° amine Benzaldehyde cyanohydrin 2-Amino-1-phenylethanol Ni+CHC OH N OH CHCH 2 NH22 H2 LiAlH4 also works well... But…what about Pd/C and H2 Chemistry 318N Oxidation and Reduction
Aldehydes are oxidized to carboxylic acids by a variety of oxidizing agents and it is possible to do some selective reduction reactions -4 -2 0 +2 +4 Oxidation Reduction CH4 CH3OH H C H O C OH O H O C O 12 Chemistry 318N Reduction
Aldehydes can be reduced to 1° alcohols and ketones to 2° alcohols. In addition, the C=O group can be reduced to a -CH2- group Aldehydes Can be Reduced to Ketones Can be Reduced to O O OH RCH RCH2 OH RCH3 RCR' RCHR' RCH2 R' Chemistry 318N Metal Hydride Reduction
The most selective reagents for the reduction of aldehydes and ketones are NaBH4 and LiAlH4 – both are sources of hydride ion, H:-, a very powerful nucleophile Hydride ionLithium aluminum hydride (LAH) Sodium borohydride •• H H H H H-B-H H-Al-HLi +Na + H 15 Chemistry 318N Examples: Lithium Aluminum Hydride Aldehyde Ketone O CH3(CH2)5CH CH3(CH2)5CH2OH 1. LiAlH4 diethyl ether 2. H2O O (C6H5)2CHCCH3 1. LiAlH4 diethyl ether 2. H2O OH (C6H5)2CHCHCH3 Chemistry 318N neither NaBH4 or LiAlH4 reduces isolated double bonds H OH O 1. LiAlH4 diethyl ether 2. H2O Selectivity 16 Chemistry 318N Example: Catalytic Hydrogenation + H2 O Pt ethanol H OH Chemistry 318N Selectivity in Reduction
LiAlH4 reduces any and all carbonyl compounds to the corresponding alcohols
NaBH4 only reduces aldehydes and ketone 17 Chemistry 318N Catalytic Reduction
Catalytic reductions are generally carried out from 25° to 100°C and from 1 to 5 atm H2
Carbon-carbon double bonds can be selectively reduced using Rhodium catalysts H2/Rh O NaBH4 MeOH OH O O Chemistry 318N Hydrogenolysis of benzylic carbonyls • Palladium catalysis of hydrogenation reduces only benzylic C-O bonds to methylene groups. • Benzyl ethers, aldehydes and alcohols are also reduced to the corresponding methylene group O OHH2 , Pd/C O H2 , Pd/C