1. Chemistry 125: Lecture 18 Amide, Carboxylic Acid, and Alkyl Lithium
The first half of the semester ends by analyzing three functional groups in terms of the interaction of localized atomic or pairwise orbitals. 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.
Synchronize when the speaker finishes saying “…our theoretical study of bonds and reactivity.” Synchrony can be adjusted by using the pause(||) and run(>) controls.
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2. Four Functional Groups: Carbonyl Amide Carboxylic Acid Alkyl Lithium
(then we’ll have a complete change of perspective)

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

4. *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

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

6. 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)

7. Acidity of Carboxylic Acids
R-OH
pKa ~16
R-O + H+
R-C O OH
pKa ~5
+ H+
R-C O
HOMO/LUMO 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

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

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

10. Rotate to superimpose the red lobes.
LUMO+1 ()
3-Center
2-Electron
Bonds
use 2 AOs
of each Li
LUMO ()
Dimerization
Two vacant
Li+ AOs
stabilize
unshared
pair of C
Aggregation of CH3Li

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

12. Aggregation of (CH3Li)4 • 4 CH3OCH3 H3C CH3 O : LUMO 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.
Last Valence
AO of 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
HOMO
(1 of 4)
Aggregation of (CH3Li)4
• 4 CH3OCH3

13. 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!

14. How Did They Know?

15. 17th Century
1800
Lavoisier
Oxidation
1900
Planck
Quantization
Newton
Gravitation
Bacon
Instauration
Luther
Reformation
Columbus
Navigation
2000 Us
1700
1600
Robt. Hooke
( )
1500
Copernicus
Revolution
Hooke (1665)
Science & Force Laws
Development of
the Organic
Structural Model
Electron bonds:
observation
&
quantum
mechanics

16. Greek symbols denote substituent positions.
Yale Chemistry 1901S
Cf.
Clairvoyant Benzene  
Greek symbols denote substituent positions.

17. Sheffield Chemistry Lab (SSS)
(only quantitative tool)

18. Analytical Balances Were Not Portable
Yale Chemistry 1901S
Quantitative Tools?
Burettes
Balance
C. Mahlon Kline (1901S)
Analytical Balances Were Not Portable

19. Kline Chemistry Laboratory (1964)
Kline Biology Tower (1965)
Kline Chemistry Laboratory (1964)

20. Quartz

21. Silliman Crystal

22. Silliman Crystal

23. Boyle Lavoisier

24. Berzelius etc.

25. Wöhler/Liebig

26. Genealogy

27. GenealogyBottom

28. Genealogy Top

29. End of Lecture 18 Oct. 15, 2008
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