{[ promptMessage ]}

Bookmark it

{[ promptMessage ]}

Chapter 17 (Lecture #15)

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

Info iconThis preview shows pages 1–8. Sign up to view the full content.

View Full Document Right Arrow Icon
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.
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
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: -
Background image of page 2
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.
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
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
Background image of page 4
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: =
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
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 =
Background image of page 6
Acyl Chlorides COH O = benzoic acid + SOCl 2 thionyl chloride (bp 75-76 o C) heat C Cl O = benzoyl chloride + SO 2 + HCl The acyl chlorides are usually isolated and purified, often by distillation.
Background image of page 7

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Image of page 8
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}