Chemistry 3720 - rganic 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 ngel Goggles Lab coat Bound notebook 1
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/ 2
Chemistry Computer Lab North end of Ward Beecher on the 5th floor Dell Pentium 4 machines ewlett Packard network laserjet printers Student assistant (?) All PC s have MS ffice, ChemDraw, ChemSketch, ACD NMR prediction software, Spartan molecular modeling package, Netscape Navigator and MS Internet xplorer pen 9-5 Mon through Fri (see lab door for schedule) ass 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 rganic Chemistry? rganic Chemistry chemical synthesis New Materials materials chemistry New Compounds medicinal chemistry New Medicines Biochemistry and Chemical Biology Nanotech, ngineering Proteomics, Genetics Pharmacy, Medicine 3
Chemistry 3719-3720 3720 C ~1800 rganic Chemistry : the chemistry of natural products based on carbon 2008 rganic Chemistry : molecular engineering 3720 verview 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 nols and enolates in the formation of C-C bonds 19 Carboxylic acids preparation and uses 20 Nucleophilic acyl substitution 21 ster enolates formation and uses in C-C bond formation 22 Chemistry of amines 25 verview of carbohydrate chemistry 26 verview of lipid chemistry 27 verview of amino acid, peptide and protein chemistry Chapter 12 - Reactions of Benzene - AS 12.1 Introduction to benzene vs. alkenes 12.2 Mechanistic principles of lectrophilic Aromatic Subsitution 12.3 Nitration of benzene, reduction to aminobenzenes 12.4 Sulfonation of benzene 12.5 alogenation 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 AS 12.10 Nitration of toluene - rate and regioselectivity 12.11 Nitration of -benzene - rate and regioselectivity 12.12 Substituent effects in AS: Activating Substituents 12.13 Substituent effects in AS: Strongly Deactivating Substituents 12.14 Substituent effects in AS: alogens 12.15 Multiple substituent effects in AS 12.16 Regioselective synthesis of disubstituted aromatic compounds 12.17 Substitution in Naphthalene 12.18 Substitution in heterocyclic aromatic compounds 4
Introduction Benzene vs. Alkenes no heat dark no heat dark no colour change (no reaction) Completely delocalized (6) pi system lends stability (aromatic) 12.2 Mechanistic Principles of AS Alkenes react by addition Y Y Y Benzene reacts by substitution Y Y - Y Resonance-stabilized cation 5
General Mechanism of AS on Benzene nergy diagram for AS in benzene Figure 12.1 lectrophilic Aromatic Substitutions on Benzene 12.3 Nitration N3, 2S 4 N 2 12.4 Sulfonation S 3, 2S 4 S 3 12.5 alogenation 2, Fe 12.6 Friedel-Crafts Alkylation of Benzene C 2 C 2 Al 3 () 3C Al 3 C 3C Al 3 C Problems: Alkyl groups may rearrange during reaction Products are more reactive than benzene Uses: Alkyl benzenes readily oxidized to benzoic acids using KMn 4 6
12.7 Friedel-Crafts Acylation of Benzene RC C R Al 3 3C C C 3 Al 3 Al 3 RC RC R C Products react more slowly than benzene - cleaner reaction No carbocation rearrangements 12.8 Alkylbenzenes via Acylation/Reduction C R Zn, (emmensen) or N 2N 2, K heat (Wolff-Kischner) C R Al 3 Zn, Make the acyl benzene first (clean, high yielding reaction) Reduce the ketone group down to the methylene (C= to C 2 ) Avoids rearrangement problems, better yields Aminobenzenes via Nitration/Reduction (not in text) N Sn, N N3, 2S 4 N 2 Sn, N 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 7
12.9 Activation and Deactivation by Substituents (Rates) X X N 3, 2S 4 N 2 0.000025 1.0 25 Relative rates in nitration reaction now bringing in a second substituent 12.9 Nitration of Toluene vs Nitration of (Trifluoromethyl)benzene( N 3, 2S 4 N 2 + + N 2 is said to be an ortho/para director (o/p director) - Regioselectivity N 2 63% 3% 34% N 3, 2S 4 N 2 + + N 2 is said to be a meta director (m director) - Regioselectivity N 2 6% 91% 3% 12.10 Rate and Regioselectivity in Nitration of Toluene N 3, 2S 4 N 2 + + N 2 N 2 63% 3% 34% Fig. 12.5 nergy diagrams for toluene nitration (vs. benzene) 8
12.11 Rate and Regioselectivity in Nitration of C 6 5 N 3, 2S 4 N 2 + + N 2 N 2 6% 91% 3% Fig. 12.6 nergy diagrams for C 6 5 nitration (vs. benzene) 12.12 Substituent ffects Activating Substituents General : all activating groups are o/p directors halogens are slightly deactivating but are o/p directors strongly deactivating groups are m directors R Activating Substituents R RC alkyl hydroxyl alkoxy acyloxy N 3, 2S 4 N 2 xample: + N 2 Alkyl groups stabilize carbocation by hyperconjugation Lone pairs on (and others like N) stabilize by resonance 12.13 Subst. ffects Strongly Deactivating Substituents C R C C C R C aldehyde ketone carboxylic acid acyl chloride ester N C S 2N nitrile sulfonic acid nitro xample: N 2 2, Fe N 2 Second substituent goes meta by default best carbocation 9
12.14 Substituent ffects alogens X X X X = F,, X = F,, Reactivity (i.e. rate) is a balance between inductive effect (W) and resonance effect (D) larger,, I do not push lone pair into pi system as well as F,, N, which are all first row (2p) xample: N 3, 2S 4 N 2 + + N 2 Regioselectivity - second substituent goes o/p better carbocations N 2 30% 1% 69% 12.15 Multiple Substituent ffects N N 3C 2, acetic acid Al 3 99% 87% 2, Fe N 3, 2S 4 N 2 N 2 N 2 C() 3 C() 3 86% 88% Interplay between power of directing group and size of substituents 12.16 Regioselective Synthesis of Disubstituted Derivs. N 2 C 2 C 2 N 2 ave to be careful about when to introduce each substituent Remember isomers (e.g. o/p mixtures) may be separated 10
12.17-12.18 12.18 Substitution in ther Aromatic Systems 12.17 Naphthalene C but not Al 3 90% 12.18 eterocycles S 3, 2S 4 S 3 N gs 4, 230 o C N 3C BF 3 11