Chemistry 242-002

Organic Chemistry II

with Professor Virgil Percec

Tue. And Thu. 9:00 AM-10:30 AM

CalendarWeek Class Dates (Tues-Thurs) Class Content:

Solomons,Orgnic Chemistry, 9th Edition

1 Th, Jan 17 (Taught by B. Rosen) Chapters 13

2 T Jan 22(Taught by B. Rosen);Th Jan 24 Chapters 13, 14

3 T Jan 29; Th Jan 31 Chapters 14, 15

4 T Feb 5; Th Feb 7 Chapters 15

Exam 1 – Thursday – Feb 7 Chapters 13, 14, 15

5 T Feb 12; Th Feb 14 Chapters 16

6 T Feb 19; Th Feb 21 Chapters 16, 17

7 T Feb 26; Th Feb 28 Chapters 17, 18

8 T Mar 4; Th Mar 6 Chapters 18

Exam 2 – Tuesday – Mar 4 Chapters 16, 17, 18

Spring Break: March 10-14 no classes

9 T Mar 18; Th Mar 20 Chapters 19

10 T Mar 25; Th Mar 27 Chapters 19, 20

11 T Apr 1; Th Apr 3 Chapters 20, 21

12 T Apr 8; Th Apr 10 Chapters 21

Exam 3 – Tuesday – Apr 8 Chapters 19, 20, 21

13 T Apr 15; Th Apr 17 Chapters 22

14 T Apr 22; Th Apr 24 Chapters 22, 23

15 T Apr 29 Chapters 24, 25

Exam 4 – Tuesday – Apr 29 Chapters 22, 23, 24, 25

Review Session for Final Exam TBA

Final Exam – Tuesday, May 13, 9:00 am – 11:00 am (Schedule from Registrar) Location TBA

Contact and Other Information

Professor Virgil Percec E-mail:

percec@sas.upenn.edu Office: Vagelos Labs

Room 4003 Office hours: T-Th

10:30 am - 12:30 pm or by appointment

Brad Rosen E-mail:

bradr@sas.upenn.edu Office: Vagelos Labs

Room 4080 Office Hours Thu Jan

17th and Tue Jan 24th 10:30 am – 12:30 pm

Class info on Blackboard: https://courseweb.upenn.edu/Sign-up for Workshops: http://www.penntutoring.info/orgochem/

Course Policy Text & Other Requirements: (packaged at considerable price

savings): Solomons, Organic Chemistry, 9th Edition (John Wiley & Sons); Solomons, Study Guide and Solutions Manual for Solomons 9th Edition (John Wiley & Sons); Hehre, Shusterman & Nelson; Stull, Science on the Internet; John Wiley & Sons Molecular Model Set for Organic Chemistry. Students must read the assigned chapters before and after lectures for complete understanding of the material. Problem solving is an essential part of the course, and you should always try to do the problems before looking up the answers. Always read questions carefully when solving problems, both in the homework and in the tests.

Recitations & Workshops: teaching assistants and specific rooms are assigned for recitations and workshops and you are encouraged to take advantage of as many of these sessions as you can.

Some more Course Policy Exams, Grading & Regrading: there will be four exams and one cumulative

final. There are no re-exams and no exams are dropped. However, in case of illness, etc. with an appropriate excuse, given before rather than after the exam, a student may be allowed to miss and reschedule one exam. I expect that A- to A+ will be given for final scores of 80 or 85 to 100% and B- to B+ for final scores of 60 or 70 to 80 or 85%. A very good class is expected to obtain up to 65 or 70% A and B. Regrading must be done within two days from the time the exam is returned. Questions must be directed to the grader in writing. You must not write on your exam in any fashion until after it has been regraded. Mid-Term Exams are scheduled for 5:00 – 7:00 PM in the locations posted above.

Drops, Withdrawals, or Incompletes: the deadlines for dropping or withdrawing must be rigorously observed.

Final grades: Final exams are scheduled by the Registrar’s office. Students missing a final examination must obtain permission to take the make-up exam the following semester (also scheduled by the registrar’s office) from an advisor in the SAS Dean’s office. The organic faculty has adopted a policy of not posting grades. You must obtain your grade by requesting in writing via email.

Please Direct all Questions Regarding Course Policy to Professor Percec

Lecture 1: Conjugated Unsaturated Systems

Chapter 13 in Solomons 9/e

What Are Conjugated Unsaturated Systems

Any system where there is a p-orbital adjacent to a double (or triple) bond

allyl radical

allyl cation

1,3-butadiene

Archetypal Conjugated Unsaturated Systems

Motivation: Synthetic Target

One often desires to make or study Medicinal Natural Products Containing Conjugated Unsaturated Systems

O

OOHHOH3C

O

H3C

H

H

H

Cortisone

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

H3C

CH3

Beta-Carotene

O

OO

H3C

OCH3

OH

O

O

O

O

ON CH3

OHOHH3C

Neocarzinostatin Chromophore

Motivation: Unique Reactivity

X H Allylic Functionalization

Nu E

E

Nu

Mixture of Enatiomers

+

OOO

O

1,2 Additon

1,4 (Michael) Addition

Diels-Alder 4+2 Cycloadditon

O

O

O

O

Motivation: Biology Vision

Allylic Substitution and the Allylic Radical

Recall from Chapter 8: Chlorination of Double Bond

Cl2light or heat

2Cl

Cl

Initiation

Chain Propogation 1

Chain Propogation 2

Cl

Cl Cl Cl Cl

Indeed at low temperature:

X2

CCl4

X

X Addition Reaction

But at high temperature or low X2 Concentration

X2X + HX Allylic Substitution

Cl + Cl H

H

H

H

HH

Allylic Hydrogens

Vinylic Protons

Brief Note on Nomenclature

H

H H

Acetylinic Proton

Propargyl Protons

Allylic Substitution and the Allylic Radical

Mechanism for Allylic Chlorination

Cl2light or heat

2ClInitiation

Chain Propogation 1

Chain Propogation 2

HH

H

Cl

Allylic Radical

+ HCl

Cl Cl Cl+ Cl

Why Allyl versus Vinyl or Alkyl Substitution ?

Allylic versus Vinylic Substitution

Allylic Proton is easier to homolyze by 96 kJ/mol

Allylic Bromination

OO N

Br

N-bromo-succinimide

light or ROOR OO N+Br Initiation

H+ Br + HBr

Br BrBr +Br

Propogation 1

Propogation 2

OO N

Br

+ HBr OOHN

+ Br2Propogation 3

O

O

N BrH +

General Reaction:

Mechanism:

Br + OOHNlight or ROOR

CCl4

Note: N-chloro-succinimide and N-iodo-succinimide exist and react in a similar way

Rules of Resonance

1) The most important rule of resonance is that resonance structures are not real. They are merely a tool for rationalizing chemical behavior. We will revisit this in terms of the allylic and other conjugated systems.

Rules of Resonance

2) In resonance we move only electrons, not atoms. And when we do it is usually π electrons.

H3C CH CH CH2 H3C CH CH CH2 H2C CH2 CH CH2

O OH

O

H

H

B-

Processes which involve “resonance” of atoms such as keto-enoltautomerization (Chapter 17) are true chemical equilibria with where each Isomer truely exists in solution

Rules of Resonance

3) All resonance structures must be true Lewis Structures (Chapter 1.5)

4) Resonance structures must have the same

number of unpaired electrons.

1 unpaired electron 3 unpaired electron

These are not in resonsance, as they are systems in different spin states.

Rules of Resonance

5) Another very important rule is that systems in resonance need to be coplanar.

transoid 1,3 Butadiene coplanarand in resonance

However 2,3-di-tert-butyl-1,3-Butadiene is twisted out of planeand is not in resonance

Rules of resonance

6) For reason which will be explained shortly, the energies of structures in resonance are always lower than those of their prototypical resonance forms.

7) Equivalent resonance structures make equivalent contributions to energies of the resonating compound

8) The more stable the resonance structure the larger its contribution

Assessing Resonance Structure Stability

1) The more covalent bonds the better the structure.

2) The more complete valance shells the better the structure.

3) The less charge separation the better.

Source of Allylic Radical Stability: Resonance

H

H

H

H

HH

H

H

H

H

H

H

H

H

H

1/2 1/2H

H

H

H

H

or

H

H

H

H

HResonance in the Allyl Radical 1

2

3

One explanation for the peculiar stability of the Allyl Radical is through implications of resonance.

Allyl Cation also Stabilized via Resonance ?

H

H

H

H

HH

H

H

H

H

H

H

H

H

H

1/2 1/2H

H

H

H

H

or

H

H

H

H

HResonance in the Allyl Radical 1

2

3

Indeed according to suggested stability via resonance , the allyl cation is unusually stable

CC

CC

>C

C

C

C> C

CC

H

H>

CC

C

H>

CC

H

H>

H

H H

Substuted allylic > 3° > Allyl > 2° > 1° > Vinyl

Resonance Structures are Just A Tool

Keep in mind that resonance structures do not really exist.

Resonance Structures allow a chemist to quickly ascertain stabilities and relativities of compounds from their line drawings.

More accurate energies and electron distributions require computational chemistry.

Molecular Orbital Description of Ethene

E=α+β

E=α-β

The Molecular Orbital (MO) Approach to the Allyl System

E=α

E=α-1.41β

E=α+1.41β

Polyunsaturated Systems:Nomenclature and Classification

H2C C CH2

Conjugated Poly Unsaturated Systems

buta-1,3-diene

(E)-penta-1,3-diene

(2E,4E)-hexa-2,4-diene

(2Z,4E)-hexa-2,4-diene

(2E,4E,6E)-octa-2,4,6-triene

cyclohexa-1,3-diene

1 3

pent-1-en-4-yne

cyclohexa-1,4-diene

propa-1,2-diene

Non-conjugated Poly Unsaturated Systems

Cumulated Diene

aka allene

penta-1,4-diene

14

1

4

CH2 n

AKA isolated dienes

Molecular Orbital Description of 1,3 Butadiene

E=α+β

E=α-β

E=α+1.62β

E=α+0.62β

E=α-0.62β

E=α-1.62β

Conformations of 1,3 Butadiene

s-trans-1,3-butadienes-cis-1,3,butadiene

free rotation

lower energyrequired for certainreaction

1.34 Å1.47 Å

Stability of Conjugated Dienes

Conjugative Stability

CompoundEquivalents of Hydrogen Added

ΔHº (kJ/mol) Conjugative Stability

1-Butene 1 -127

1-Pentene 1 -126

trans-2-Pentene 1 -115

1,3 Butadiene 2 -239 15

trans-1,3-Pentadiene 2 -226 15

1,4-Pentadiene 2 -254

1,5-Hexadiene 2 -253

UV-Vis Spectroscopy

Beer’s LawA=ε x c x l = log (Io/I)ε=extinction coefficient/molar absorptivityc=concentrationl= path length

UV-VIS of Extended trans π-systems

Compound

ethene

1,3-butadiene

1,3,5-hexatriene

1,3,5,7-octatetraene

1,3,5,7,9-decapentaene

1,3,5,7,9,11-dodecahexaene

165

217

256

290

334

364

15,000

21,000

50,000

85,000

125,000

138,000

max

Relationship Between Number of Conjugated Double Bonds and λ max

y = 39.429x + 133

150

200

250

300

350

400

1 2 3 4 5 6

Relationship of Number of Conjugated Double Bonds to Extinction Coefficient

10000

30000

50000

70000

90000

110000

130000

150000

1 2 3 4 5 6

All π π* transitions

Electrophillic Attack on Conjugated Dienes

Cl

ClHCl

25 °C1,3 butadiene 3-Chloro-1-butene 1-Chloro-2-butene (78%) (22%)

HCl

25 °C

Cl

H (1,2 Addition)

HCl

25 °C ClH (1,4 Addition)

Expected Markovnikov Product

Mechanism of Electrophillic Addition to Conjugated Dienes

HCl +

allyl cation

Step 1:

Step 2:

Cl

Cl+ b

a Cl

H (1,2 Addition)

ClH (1,4 Addition)

a

b

HCl +

Comparison of 1,4 AdditionCl

ClHCl

25 °C1,3 butadiene 3-Chloro-1-butene 1-Chloro-2-butene (78%) (22%)

Br

BrHBr

40 °C1,3 butadiene 3-Bromo-1-butene 1-Bromo-2-butene (80%) (20%)

Br

BrBr2

-15 °C1,3 butadiene 1,2-dibromo-1-butene 1,4-dibromo-2-butene (54%) (46%)

Br Br

Kinetic versus Thermodynamic Control

Kinetic Control

Thermodynamic Control

Diels-Alder Reaction:The Basics

O

O

O

Maleic anhydide(dienophile)

s-cis-1,3-butadiene(diene)

O

O

O

Simplest Diels Alders Reaction

200 C

sealed tube(20%)

H3C

H3CO2C CH3

CH3

Cl CN

Works Better with Electron Rich Dienes and Electron Poor Olefins

H3C CH3ClCN

H3C

MeO2C130 °C

85%

S-cis diene required, s-trans does not work