hemistry 3720 - rganic hemistry II Dr. Peter Norris 6014 Ward Beecher (330) 941-1553 pnorris@ysu.edu http://www.as.ysu.edu/~pnorris/public_html Recitation Teaching Assistants Abdul-Basit Alhassan, Adam ox Lecture needs: arey Molecular models Adobe Acrobat Reader Web access Lab needs: Pavia, Lampman, Kriz and Engel Goggles Lab coat Bound notebook 1
3720 Web Resources http://www.as.ysu.edu/~chemistry http://www.as.ysu.edu/~pnorris/public_html (ontains 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 hemistry 3720 page includes practice problems on NMR spectroscopy (hapter 13) Message board linked to 3720 home page for asking questions, especially before exams 2
hemistry omputer Lab North end of Ward Beecher on the 5th floor Dell Pentium 4 machines ewlett Packard network laserjet printers Student assistant (?) All P s have MS ffice, hemdraw, hemsketch, AD NMR prediction software, Spartan molecular modeling package, Netscape Navigator and MS Internet Explorer pen 9-5 Mon through Fri (see lab door for schedule) hemistry 3720 (and labs) Lectures Structure and nomenclature of compounds and groups Physical properties and analysis of materials Reactivity and transformations with reagents Importance of organic compounds in society Labs Glassware and equipment used to prepare organics Instrumentation used to analyze compounds Writing detailed reports of lab preparations 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 (>65%) in order to pass 3720/3720L Misconduct: Any copying or other forms of cheating will be dealt with severely 3
rganic hemistry at YSU B.S. and M.S. degrees in hemistry State of the art instrumentation (>$1,000,000 worth) Active research programs (Norris and Jackson) Student involvement in 3719/20, 4850, 6990 Students present at regional and national meetings Undergrad and graduate students publish in journals Research pportunities Summer 2006 All areas of science - National Science Foundation Research Experience for Undergraduates (REU program) Typically: $3000 stipend for 10 weeks Accommodation and meals often included Need to apply by ~April, need 3 letters from faculty Good way to find out if grad school interests you www.nsf.gov Why a year of rganic hemistry? rganic hemistry chemical synthesis New Materials materials chemistry New ompounds medicinal chemistry New Medicines Biochemistry and hemical Biology Nanotech, Engineering Proteomics, Genetics Pharmacy, Medicine 4
hemistry 3719-3720 ~1800 rganic hemistry : the chemistry of natural products based on carbon 2004 rganic hemistry : molecular engineering 3720 verview of hapters 12 Reactions of benzene electrophilic aromatic substitution 13 Spectroscopy how do you know what the structure is? 14 - bond formation using organometallic compounds 15 hemistry of alcohols, diols and thiols 16 hemistry of ethers, epoxides and sulfides 17 Aldehydes and ketones preparation and uses 18 Enols and enolates in the formation of - bonds 19 arboxylic acids preparation and uses 20 Nucleophilic acyl substitution 21 Ester enolates formation and uses in - bond formation 22 hemistry of amines 25 verview of carbohydrate chemistry 26 verview of lipid chemistry 27 verview of amino acid, peptide and protein chemistry hapter 12 - Reactions of Benzene - 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 alogenation of benzene 12.6 Friedel-rafts alkylation of benzene 12.7 Friedel-rafts 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 -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: alogens 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 Benzene vs. Alkenes no heat dark no heat dark no colour change (no reaction) ompletely delocalized (6) pi system lends stability (aromatic) 12.2 Mechanistic Principles of EAS Alkenes react by addition E Y E E Y Y Benzene reacts by substitution E Y E Y - Y E Resonance-stabilized cation 6
General Mechanism of EAS on Benzene Energy diagram for EAS in benzene Figure 12.1 Electrophilic Aromatic Substitutions on Benzene 12.3 Nitration N3, 2 S 4 N 2 12.4 Sulfonation S 3, 2 S 4 S 3 12.5 alogenation 2, Fe 12.6 Friedel-rafts Alkylation of Benzene 2 2 Al 3 () 3 Al 3 3 Al 3 Problems: Uses: Alkyl groups may rearrange during reaction Products are more reactive than benzene Alkyl benzenes readily oxidized to benzoic acids using KMn 4 7
12.7 Friedel-rafts Acylation of Benzene R R Al 3 3 3 3 Al 3 Al 3 R R R Products react more slowly than benzene - cleaner reaction No carbocation rearrangements 12.8 Alkylbenzenes via Acylation/Reduction R Zn, (emmensen) or N 2N 2, K heat (Wolff-Kischner) R Al 3 Zn, Make the acyl benzene first (clean, high yielding reaction) Reduce the ketone group down to the methylene (= to 2 ) Avoids rearrangement problems, better yields Aminobenzenes via Nitration/Reduction (not in text) N Sn, N N3, 2 S 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 8
12.9 Activation and Deactivation by Substituents (Rates) X X N 3, 2 S 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, 2 S 4 N 2 + + N 2 is said to be an ortho/para director (o/p director) - Regioselectivity N 2 63% 3% 34% N 3, 2 S 4 N 2 + + N 2 N 2 6% 91% 3% is said to be a meta director (m director) - Regioselectivity 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 Energy diagrams for toluene nitration (vs. benzene) 9
12.11 Rate and Regioselectivity in Nitration of 6 5 N 3, 2 S 4 N 2 + + N 2 N 2 6% 91% 3% Fig. 12.6 Energy diagrams for 6 5 nitration (vs. benzene) 12.12 Substituent Effects 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 Activating Substituents R R R alkyl hydroxyl alkoxy acyloxy N 3, 2S 4 N 2 Example: + N 2 Alkyl groups stabilize carbocation by hyperconjugation Lone pairs on (and others like N) stabilize by resonance 12.13 Subst.. Effects Strongly Deactivating Substituents R R aldehyde ketone carboxylic acid acyl chloride ester N S 2 N nitrile sulfonic acid nitro Example: N 2 2, Fe N 2 Second substituent goes meta by default best carbocation 10
12.14 Substituent Effects alogens X X X X = F,, X = F,, Reactivity (i.e. rate) is a balance between inductive effect (EW) and resonance effect (ED) larger,, I do not push lone pair into pi system as well as F,, N, which are all first row (2p) Example: N 3, 2 S 4 N 2 + + N 2 Regioselectivity - second substituent goes o/p better carbocations N 2 30% 1% 69% 12.15 Multiple Substituent Effects N N 3 2, acetic acid Al 3 99% 87% 2, Fe N 3, 2S 4 N 2 N 2 N 2 () 3 () 3 86% 88% Interplay between power of directing group and size of substituents 12.16 Regioselective Synthesis of Disubstituted Derivs. N 2 2 2 N 2 ave to be careful about when to introduce each substituent Remember isomers (e.g. o/p mixtures) may be separated 11
12.17-12.18 12.18 Substitution in ther Aromatic Systems 12.17 Naphthalene but not Al 3 90% 12.18 eterocycles S 3, 2S 4 S 3 N gs 4, 230 o N 3 BF 3 12