1 3720 Web Resources 3720 Web Resources - - PDF document

1

Chemistry 3720 Chemistry 3720 -

• Organic Chemistry II

Organic Chemistry II

• Dr. Peter Norris

6014 Ward Beecher (330) 941-1553 pnorris@ysu.edu http://www.as.ysu.edu/~pnorris/public_html Lecture needs: Carey Molecular models Adobe Acrobat Reader Web access Lab needs: Pavia, Lampman, Kriz and Engel Goggles Lab coat Bound notebook

2

3720 Web Resources 3720 Web Resources

http://www.as.ysu.edu/~chemistry http://www.as.ysu.edu/~pnorris/public_html

(Contains lab and lecture material, problem sets and old exams) Need the Adobe Acrobat Reader to download printed material, links to the site are on the web page Chemistry 3720 page includes practice problems on NMR spectroscopy (Chapter 13) Message board linked to 3720 home page for asking questions, especially before exams

http://www.as.ysu.edu/~chem/ http://www.as.ysu.edu/~pnorris/

3

Chemistry Computer Lab Chemistry Computer Lab

North end of Ward Beecher on the 5th floor Dell Pentium 4 machines Hewlett Packard network laserjet printers Student assistant (?) All PC’s have MS Office, ChemDraw, ChemSketch, ACD NMR prediction software, Spartan molecular modeling package, Netscape Navigator and MS Internet Explorer Open 9-5 Mon through Fri (see lab door for schedule)

Class Requirements (see syllabus) Class Requirements (see syllabus)

3720 Lecture: 3 term exams, 100 points each 1 Final exam, 200 points No dropped tests 3720 Lab: 100 points total. Must pass lab (>60%) in order to pass 3720/3720L Misconduct: Any copying or other forms of cheating will be dealt with severely

Why a year of Organic Chemistry? Why a year of Organic Chemistry?

Organic Chemistry

New Compounds New Medicines

New Materials Pharmacy, Medicine Nanotech, Engineering

Proteomics, Genetics

4

~1800 – Organic Chemistry : the chemistry of natural products based

• n carbon

2008 – Organic Chemistry : “molecular engineering”

Chemistry 3719 Chemistry 3719-

• 3720

3720

H C H H H

3720 Overview of Chapters 3720 Overview of Chapters

12 Reactions of benzene – electrophilic aromatic substitution 13 Spectroscopy – how do you know what the structure is? 14 C-C bond formation using organometallic compounds 15 Chemistry of alcohols, diols and thiols 16 Chemistry of ethers, epoxides and sulfides 17 Aldehydes and ketones – preparation and uses 18 Enols and enolates in the formation of C-C bonds 19 Carboxylic acids – preparation and uses 20 Nucleophilic acyl substitution 21 Ester enolates – formation and uses in C-C bond formation 22 Chemistry of amines 25 Overview of carbohydrate chemistry 26 Overview of lipid chemistry 27 Overview of amino acid, peptide and protein chemistry

Chapter 12 Chapter 12 -

• Reactions of Benzene

Reactions of Benzene -

• EAS

EAS

12.1 Introduction to benzene vs. alkenes 12.2 Mechanistic principles of Electrophilic Aromatic Subsitution 12.3 Nitration of benzene, reduction to aminobenzenes 12.4 Sulfonation of benzene 12.5 Halogenation of benzene 12.6 Friedel-Crafts alkylation of benzene 12.7 Friedel-Crafts alkylation of benzene 12.8 Alkylbenzenes via acylation then reduction 12.9 Rate and regioselectivity in EAS 12.10 Nitration of toluene - rate and regioselectivity 12.11 Nitration of CF3-benzene - rate and regioselectivity 12.12 Substituent effects in EAS: Activating Substituents 12.13 Substituent effects in EAS: Strongly Deactivating Substituents 12.14 Substituent effects in EAS: Halogens 12.15 Multiple substituent effects in EAS 12.16 Regioselective synthesis of disubstituted aromatic compounds 12.17 Substitution in Naphthalene 12.18 Substitution in heterocyclic aromatic compounds

5

Introduction Introduction – – Benzene vs. Alkenes Benzene vs. Alkenes

Br Br Br Br no heat dark Br Br no heat dark no colour change (no reaction)

Completely delocalized (6) pi system lends stability (aromatic)

12.2 Mechanistic Principles of EAS 12.2 Mechanistic Principles of EAS

Alkenes react by addition Benzene reacts by substitution

E Y E E Y Y E Y E E Y H H Y

• Resonance-stabilized cation

6

Energy diagram for EAS in benzene

Figure 12.1

General Mechanism of EAS on Benzene General Mechanism of EAS on Benzene Electrophilic Electrophilic Aromatic Substitutions on Benzene Aromatic Substitutions on Benzene

NO2

HNO3, H2SO4

H

12.3 Nitration 12.4 Sulfonation

SO3H

SO3, H2SO4

H

12.5 Halogenation

Br

Br2, Fe

H

12.6 12.6 Friedel Friedel-

• Crafts

Crafts Alkylation Alkylation of Benzene

• f Benzene

Problems: Alkyl groups may rearrange during reaction Products are more reactive than benzene Uses: Alkyl benzenes readily oxidized to benzoic acids using KMnO4

H

H

H

7

12.7 12.7 Friedel Friedel-

• Crafts

Crafts Acylation Acylation of Benzene

• f Benzene

Products react more slowly than benzene - cleaner reaction No carbocation rearrangements

C

H

RCCl AlCl3

H

AlCl3 O

CCH3 O R O RCCl O AlCl3 RC O R C O

12.8 12.8 Alkylbenzenes Alkylbenzenes via via Acylation Acylation/Reduction /Reduction

Make the acyl benzene first (clean, high yielding reaction) Reduce the ketone group down to the methylene (C=O to CH2) Avoids rearrangement problems, better yields

C R C O R H H Zn, HCl (Clemmensen)

• r

Aminobenzenes Aminobenzenes via Nitration/Reduction (not in text) via Nitration/Reduction (not in text)

Make the nitro benzene first, clean high yielding reaction Reduce the nitro group down to the amine Difficult to introduce the amino group by other methods

N N O O H H Sn, HCl

NO2

HNO3, H2SO4

H

N H H Sn, HCl

8

12.9 Activation and Deactivation by 12.9 Activation and Deactivation by Substituents Substituents (Rates) (Rates)

Relative rates in nitration reaction now bringing in a second substituent NO2

HNO3, H2SO4

X X CF3 CH3 H 0.000025 1.0 25 12.9 Nitration of Toluene 12.9 Nitration of Toluene vs vs Nitration of ( Nitration of (Trifluoromethyl)benzene Trifluoromethyl)benzene CH3 is said to be an ortho/para director (o/p director) - Regioselectivity CF3 is said to be a meta director (m director) - Regioselectivity

12.10 Rate and 12.10 Rate and Regioselectivity Regioselectivity in Nitration of Toluene in Nitration of Toluene

• Fig. 12.5 – Energy diagrams for toluene nitration (vs. benzene)

9

12.11 Rate and 12.11 Rate and Regioselectivity Regioselectivity in Nitration of CF in Nitration of CF3

3C

C6

6H

H5

5

• Fig. 12.6 – Energy diagrams for CF3C6H5 nitration (vs. benzene)

12.12 Substituent Effects 12.12 Substituent Effects – – Activating Activating Substituents Substituents

Alkyl groups stabilize carbocation by hyperconjugation Lone pairs on O (and others like N) stabilize by resonance General : all activating groups are o/p directors halogens are slightly deactivating but are o/p directors strongly deactivating groups are m directors

R alkyl HO hydroxyl RO alkoxy RCO acyloxy O

Activating Activating Substituents Substituents

12.13 12.13 Subst

• Subst. Effects

. Effects – – Strongly Deactivating Strongly Deactivating Substituents Substituents

Second substituent goes meta by default – best carbocation

HC aldehyde C ketone C carboxylic acid C acyl chloride O O R O HO O Cl C ester O RO C nitrile S sulfonic acid O2N nitro N O HO O NO2 Br2, Fe NO2 Br Example:

10

12.14 Substituent Effects 12.14 Substituent Effects – – Halogens Halogens

Regioselectivity - second substituent goes o/p – better carbocations

Reactivity (i.e. rate) is a balance between inductive effect (EW) and resonance effect (ED) – larger Cl, Br, I do not push lone pair into pi system as well as F, O, N, which are all first row (2p)

12.15 Multiple Substituent Effects 12.15 Multiple Substituent Effects

Interplay between power of directing group and size of substituents

12.16 12.16 Regioselective Regioselective Synthesis of Synthesis of Disubstituted Disubstituted Derivs Derivs. .

Have to be careful about when to introduce each substituent Remember – isomers (e.g. o/p mixtures) may be separated

11

12.17 12.17-

• 12.18 Substitution in Other Aromatic Systems

12.18 Substitution in Other Aromatic Systems

12.17 Naphthalene 12.18 Heterocycles