Chapter 17 (Lecture #15)

Chapter 17 (Lecture #15) - Nucleophilic Substitution at...

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Unformatted text preview: Nucleophilic Substitution at Acyl Carbon Aldehydes and ketones undergo nucleophilic additions to the carbonyl group: C=O R R' : : + Nu:- C-O : : :- R R' Nu tetrahedral intermediate Nu-H C-O-H + Nu:- : : R R' Nu The typical reaction with carboxylic acids and their derivatives is nucleophilic substitution . The first step is nucleophilic addition to give the tetrahedral intermediate, but the presence of a good leaving group at the carbon center results in a cleavage reaction and regeneration of the carbonyl group. Nucleophilic Substitution at Acyl Carbon C=O R : : + Nu:- X nucleophilic addition C-O : : :- R Nu tetrahedral intermediate X C-O : : :- R Nu X cleavage C=O R :: Nu + X:- Example: Hydrolysis of an Acyl Chloride R-C- Cl :O: = + :O-H H : nucleophile nucleophilic addition R-C- Cl :O-H H + :O: :- tetrahedral intermediate R-C- Cl :O-H H + :O: :-- Cl- cleavage R-C-O-H :O: = H : + H 2 O R-C-O-H :O: = : + : + H 3 O-H + This reaction proceeds well because of the great reactivity of the acyl chloride towards nucleophilic addition, and the good leaving group ability of Cl- in the cleavage step. Acid Catalysis R-C- X: + H-Nu: :O: = R-C- X: + :Nu: :O-H =- + protonation R-C- X : + H-Nu: :O-H = + electrophilic catalysis R-C- X: Nu-H :O-H : + tetrahedral intermediate R-C- X: Nu: :O-H : + H + deprotonation protonation of leaving group R-C- X: Nu: :O-H : + H + a better leaving group electrophilic assistance in cleavage step R-C-Nu: :O-H = + + H-X + R-C- X- Nu: :O-H : H deprotonation R-C-Nu: :O-H = + R-C-Nu: :O: = + H + acyl substitution product Important Factors in the Addition-Cleavage Reaction Reactivity of the Acyl Carbon Electronic influences that increase the electropositive character of the acyl carbon enhance the rate of nucleophilic addition. R-C- X :O: = !" ! + As the electronegativity of X increases, the rate of nucleophilic addition increases. Nu:- Stability of the Leaving Group As the stability of X:- increases, it becomes a better leaving group. R-C- X :O: : Nu- R-C-Nu + X:- :O: = Relative Reactivity of Acyl Compounds in Nucleophilic Substitution React ions The electron-withdrawing influence and l eaving group ability of X in acyl compounds leads to a general reactivity order: In general, a less reactive acyl compound can be prepared from a more reactive acyl compound. Accordingly, acyl chlorides can be converted into any of the other acyl compounds General Synthetic Scheme RC- Cl O = acyl chloride RC- OCR O = O = acid anhydride RC- OR' O = ester RC- NR'R'' O = amide > > > RCOOH RC- Cl O = Acyl Chlorides COH O = benzoic acid + SOCl 2 thionyl chloride...
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This note was uploaded on 01/20/2012 for the course CHEM 325BL at USC.

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Chapter 17 (Lecture #15) - Nucleophilic Substitution at...

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