Chemistry 125: Lecture 17 October 8, 2010 Carbonyl, Amide, Carboxylic Acid, and Alkyl Lithium The first “half” of the semester ends by analyzing four functional groups in terms of the interaction of localized atomic or pairwise orbitals. Analyzing  * C=O predicts a trajectory for attack by a high HOMO. Bürgi and Dunitz compared numerous crystal structures determined by X-ray diffraction in order to validate this prediction. Key properties of biological polypeptides derive from the mixing of localized orbitals that we associate with “resonance” of the amide group. The acidity of carboxylic acids and the aggregation of methyl lithium into solvated tetramers can be understood in analogous terms. More amazing than the power of modern experimental and theoretical tools is that their results did not surprise traditional organic chemists, who already had developed an understanding of organic structure with much cruder tools. The next quarter of the semester is aimed at understanding how our scientific predecessors developed the structural model and nomenclature of organic chemistry that we still use. For copyright notice see final page of this file

“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. Cl

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

This kind of Functional Group Analysis is the culmination of our work with Quantum Mechanics. A reasonable preparation strategy would be to discuss these Wikis in study groups and discussion sections.

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

H C  CH O HOMO LUMO Shape of "Frontier" Orbitals 2p O  C-H AON ABN >> Which is higher? 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 (Cf. 2p F >  C-H ) ±

Low LUMO LUMO Shape of "Frontier" Orbitals Poor overlap (  ) ; Poor E-match (2p O < 2p C ) AON ABN 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 45% 2p O : 55% 2p C HOMO

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) 55% 2p O : 45% 2p C e/a o 3 O holds its electrons more closely than C (1.5Å) (1.7Å) van der Waals radii ?

Bürgi-Dunitz Angle From what direction should a nucleophile HOMO approach the  * LUMO of the C=O group? until 1980s H 2 C O Nu H 2 C O Nu is better than (where Nu means “nucleophile”) Also

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

Structure Superposition from 14 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. Bürgi, J. D. Dunitz Accts. Chem. Res. 16, 153 (1983)

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

Resonance: Intramolecular HOMO/LUMO Mixing Why the Amide Functional Group is not an Amine and a Ketone C N O

vs. Amide Pyramidal NPlanar N Easy N-C RotationBarrier to Rotation Amine Carbonyl StableMore Stable Naïve PredictionExperimental Observation by 16 kcal/mole (1/4 C-N) 16 kcal/mole by 0.14Å by 0.03Å wrecks  * C=O -n N overlap HOMO LUMO Long N-CShorter N-C … Short C=OLonger C=O … net (mostly) Opposing Dipoles Strongly Dipolar (in  direction) ~1/3 e - transfer N  O Crucial for Structural Biology O C  * C=O “LUMO” n N “HOMO” NN N might as well rehybridize Partial C=N Double Bond Partial C-O Single Bond n NH 3  * C=O Basic and AcidicRelatively Unreactive Skin works Resonance as a Make & Break correction to a naïve, localized initial drawing ! (best overlap)

End of Lecture 17 Oct. 8, 2010 Continue for Optional Spartan Demo 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