1. Chemistry 125: Lecture 17 October 12, 2009 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
(to be supplemented with after-class Spartan session)

2. Shape of "Frontier" Orbitals
LUMO
Shape of "Frontier" Orbitals
Plum Pudding MOs
3dxz
(6 valence pairs) H C O 2s
2px
2py
2pz 3s
3dxy
HOMO
ABN
Low LUMO
AON
45% 2pO : % 2pC
Pairwise Mixing Analysis
Poor overlap ()
; Poor E-match (2pO < 2pC)

3. 0.03
0.1
0.3
0.01
0.003
e/ao3
C-O  Bonding
55% 2pO : 45% 2pC ?
(1.5Å)
(1.7Å)
van der Waals radii
O holds its electrons more closely than C
Nodes through nuclei (AON),
not between atoms (ABN)
mostly a p-rich hybrid atomic orbital
of Oxygen
Lower of Oxygen’s “Unshared" Pairs
some O-C bonding
with backside of C hybrid
some C-H bonding

4. until 1980s
From what direction should a nucleophile HOMO approach
the p* LUMO
of the C=O group?
H2C O Nu
is better than
(where Nu means “nucleophile”)
Also
Bürgi-Dunitz Angle

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

6. Bürgi-Dunitz Angle (110°)
Structure Superposition
from 14 Crystals (A-O)
Containing N: and C=O N R C O
from H. B. Bürgi, J. D. Dunitz
Accts. Chem. Res. 16, 153 (1983)
Bürgi-Dunitz Angle (110°)
N.B. There is another R group directly behind this one.

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

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

9. *C=O nNH3 Carbonyl vs. Amide Amine Resonance as a
HOMO
LUMO
net
Naïve Prediction
Experimental Observation
Resonance as a
Make & Break correction to
a naïve, localized initial drawing
Stable
More Stable
by 16 kcal/mole (1/4 C-N)
Long N-C
Shorter N-C …
by 0.14Å
Crucial for
Structural
Biology
Short C=O
Longer C=O …
by 0.03Å O C
*C=O “LUMO”
Pyramidal N
Planar N
! (best overlap) N N N
Easy N-C Rotation
Barrier to Rotation
16 kcal/mole
wrecks *C=O-nN overlap
Basic and Acidic
nN “HOMO”
nNH3
*C=O
Relatively Unreactive
Skin works
might as well rehybridize
(mostly) Opposing Dipoles
Partial C=N Double Bond
Strongly Dipolar
(in  direction)
Partial C-O Single Bond
~1/3 e- transfer
N  O

10. formamide HOMO :  electron pair “from” N shared with C=O creates
electric dipole

11. Repeating Unit in Protein -Helix- +
Stabilized by electrostatic “Hydrogen Bonding”
and by local planarity of C-N=C-C groups O =
(reducing backbone “floppiness” by 1/3)

12. Acidity of Carboxylic Acids
R-OH
pKa ~16
R-O + H+
R-C O OH
pKa ~5
+ H+
R-C O
HOMO-LUMO mixing stabilizes
neutral acid compared to ROH.
Predicts more uphill?
R-C O OH +
HOMO-LUMO REALLY stabilizes carboxylate anion.
R-C O
1011  stronger!
(Less “Uphill”)
higher

13. LUMO ()
LUMO+1 ()
HOMO ()
Aggregation of CH3Li

14. Aggregation of CH3Li LUMO+1 () 2HOMO () Dimerization 2LUMO+1 ()

15. Rotate to superimpose the red lobes.
BH2 H
H2B
LUMO+1 ()
3-Center
2-Electron
Bonds use
only 2 AOs
of each Li
LUMO ()
Dimerization
Vacant
Li+ AOs
stabilize
unshared
pairs of CH3
Aggregation of CH3Li

16. Aggregation of CH3Li LUMO+1 () HOMO () HOMO () LUMO+1 ()
rotated 90°
Aggregation of CH3Li

17. Aggregation of (CH3Li)4 • 4 CH3OCH3 H3C CH3 O : LUMO CH3OCH3 HOMO
NON-BONDED INTERACTIONS & SOLVENT EFFECTS ARE
A VITAL PART OF LORE.
(e.g. facilitating ionization)
Excess Ether Rips Aggregates Apart by bonding with Li AOs to form CH3Li • 3 O(CH3)2
Last Valence
AO of each Li
(vacant)
H3C
CH3 O :
LUMO
(1 of 4)
3 vacant
Li+ AOs
stabilize
unshared
pair of C.
Distorted
Cubic
Tetramer
4-Center
2-Electron
Bond
(CH3)2O
O(CH3)2
CH3OCH3
HOMO
(1 of 4)
Aggregation of (CH3Li)4
• 4 CH3OCH3

18. Spartan Demonstration you choose the functional group

19. But organic chemists were not at all surprised by what they showed!
We have seen amazing modern tools for revealing the Å / psec world of molecules:
SPM
X-ray Diffraction
Spectroscopy: IR, ESR, (NMR, etc.)
Quantum Mechanics
(computer "experiments")
But organic chemists were not at all surprised by what they showed!

20. How Did They Know?

21. 17th Century 1500 1800 1900 2000 1700 1600 Science & Force Laws Hooke
Luther
Reformation
Bacon
Instauration
Columbus
Navigation
1500
Copernicus
Revolution
Newton
Gravitation
1800
Lavoisier
Oxidation
1900
Planck
Quantization
2000 Us
1700
1600
Science & Force Laws
Hooke
Coulomb
Electron Bonds:
Observation
&
Quantum
Mechanics
Schrödinger
The Organic
Structural Model
&
Chemistry

22. End of Lecture 17 Oct. 12, 2009 Continue for Optional Spartan Demo
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23. Enol by Spartan
The narrative for this timed ppt comes after the normal lecture on the same WMA file, following some after class questions. It begins at 57’36”.
Click the forward arrow at 58’10”, after JMM says “So we want an enol. So we want to build a mol… we want to select that set of nuclei.”
Sometimes the timing malfunctions a bit, which you can get around by pressing the arrow keys, if you wish.

28. 0.003
0.03
0.3

34. End