Chemistry 125: Lecture 17 Reaction Analogies and Carbonyl Reactivity In molecular orbital terms there is a close analogy among seemingly disparate organic chemistry reactions: acid-base, S N 2 substitution, and E2 elimination. All these reactions involve breaking existing bonds, where LUMOs have antibonding nodes, while new bonds are being formed. The three-stage oxidation of ammonia by Cl 2 is analyzed in these terms. The analysis is extended to the reactivity of the carbonyl group and predicts the trajectory for attack by a high HOMO. This predicted trajectory was validated experimentally by Bürgi and Dunitz, who compared numerous crystal structures determined by X-ray diffraction. Synchronize when the speaker finishes saying “…from a new point of view.” Synchrony can be adjusted by using the pause(||) and run(>) controls. For copyright notice see final page of this file

F H Direction of HOMO approach for best overlap :OH FH OH ABN Besides creating a new bond, mixing HOMO with LUMO can break a bond where the LUMO has an AntiBonding Node. LUMO Reaction Analogies ** "Acid-Base" Make & Break

F H:OH FH OH "Acid-Base" F CH 3 :OH CH 3 OHF LUMO Reaction Analogies  "S N 2 Substitution" ABN (Could have been called S N 2 Substitution at H) Make & Break Same

Make & Break  F CH 3 :OH CH 3 OHF "S N 2 Substitution" F CH 2 CH 2 H F H:OH FH OH "Acid-Base" :OH F H OH CH 2 "E2 Elimination" ABN AON  Bonding Between Carbons This LUMO is the favorable mixture of  * C-H  * F-C ABN Make Two Break Two (Could have been called S N 2 Substitution at H) LORE! (LUMO calculation biased by stretching C-H, C-F) ? LUMO Reaction Analogies

“Oxidation” of Ammonia by Chlorine 3 NH 3 + Cl 2 H 2 N-NH 3 Cl + NH 4 Cl High HOMO? Low LUMO? n NH 3 :NH 3  * Cl 2 Cl-Cl High HOMO? Low LUMO? n NH 3 :NH 3  * N-H Cl-NH 2 -H + Cl + Cl-NH 3 +_ Low LUMO?  * Cl-N Cl-NH 2 High HOMO? n NH 3 :NH 3 Cl + NH 2 -NH 3 +_ Cl NH 4 Cl-NH 3 + Cl-NH 2 +NH 4 + H 2 N-NH 3 Cl Three Cycles of Make & BreakNH 3 s attack Cl, then H, then N.

Four Functional Groups: Carbonyl Amide Carboxylic Acid Alkyl Lithium (then we’ll have a complete change of perspective)

Functional Group Analysis Wiki due Thursday, Oct. 16

The Carbonyl Group C=O Probably the most important Functional Group in Organic Chemistry Strong AND Reactive

HOMO LUMO Shape of "Frontier" Orbitals Low LUMO 2p O  C-H AON Poor overlap (  ) ; Poor E-match (2p O < 2p C ) AON ABN >> Which is lower? nuclear charge overlap, bonding 2s 2p x 2p y 2p z 3s 3d xy 3d xz Pairwise Mixing Analysis Plum Pudding MOs (6 valence pairs) H H C O

C-O  Bonding Lower of Oxygen’s “Unshared" Pairs mostly a p-rich hybrid atomic orbital of Oxygen some O-C bonding with backside of C hybrid some C-H bonding Nodes through nuclei (AON), not between atoms (ABN)

Bürgi-Dunitz Angle From what direction should a nucleophile HOMO approach the  * LUMO of the C=O group?

Bürgi-Dunitz Angle From what direction should a nucleophile HOMO approach the  * LUMO of the C=O group? furthest from nodes

Structure Superposition from many Crystals (A-O) Containing N: and C=O Bürgi-Dunitz Angle (110°) R R C C O O N N N.B. There is another R group directly behind this one. from H. B. B ü rgi, J. D. Dunitz Accts. Chem. Res. 16, 153 (1983)

End of Lecture 17 Oct. 13, 2008 Copyright © J. M. McBride Some rights reserved. Except for cited third-party materials, and those used by visiting speakers, all content is licensed under a Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0).Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0) Use of this content constitutes your acceptance of the noted license and the terms and conditions of use. Materials from Wikimedia Commons are denoted by the symbol. Third party materials may be subject to additional intellectual property notices, information, or restrictions. The following attribution may be used when reusing material that is not identified as third-party content: J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0