Aromatic Reactions PDF

Chapter 16 Aromatic reactions 1  Electrophilic Aromatic Substitution benzene primarily undergoes electrophilic aromatic substitution— a hydrogen atom is replaced by an electrophile. reactions that keep the aromatic ring intact are favored…basically...

Chapter 16 Aromatic reactions 1  Electrophilic Aromatic Substitution benzene primarily undergoes electrophilic aromatic substitution— a hydrogen atom is replaced by an electrophile. reactions that keep the aromatic ring intact are favored…basically regeneration of the aromatic ring occurs during the reaction…. substitution occurs rather than addition so aromaticity is maintained 2  Examples of Electrophilic Aromatic Substitution Figure 16.1 3  Mechanism of Substitution all electrophilic aromatic substitution reactions occur by the same two-step mechanism: 1. addition of the electrophile E+ to form a resonance-stabilized carbocation, 2. followed by deprotonation with base. 4 The first step in electrophilic aromatic substitution forms a carbocation, three resonance structures….. carbocation in ortho and para positions only, [then loss of a H (proton)] Which reforms the aromatic ring 5 In halogenation, benzene reacts with X2 to give aryl halides a Lewis acid catalyst is needed Cl2 & Br2 work well I2 is too unreactive and F2 reacts too violently. Note: this is as if “X+” adds to the ring…regardless of mechanism on next slide 6 Chlorination proceeds by a similar mechanism. 7 Nitration and sulfonation……similar concepts As if NO2+ or HSO3+ adds to the ring 8 Generation of the electrophile in these reactions requires a strong acid…. This is the electrophile 9  Friedel–Crafts Alkylation treatment of benzene with an alkyl halide and a Lewis acid (AlCl3) forms an alkyl benzene. A carbocation adds to the ring….. This introduces alkyl groups onto the benzene ring 10 Electrophiles in Friedel–Crafts Alkylation carbocation 11 Friedel–Crafts Alkylation with Carbocation 12  Other Carbocations in Friedel–Crafts Alkylation In general, any functional group that forms a carbocation can also be used as an electrophile in the presence of benzene. Example; alkene, alcohols, etc 13 14  16.5 continued Note: mechanism is to remove the halide, then add the rest of the molecule to the ring substituting for the H 15 Note: Friedel Crafts alkylation needs to have the halide bonded to an sp3 hybridized carbon to be reactive Vinyl and aryl halides are not reactive: they cannot produce stable cations A carbocation is needed in the reaction….. 16  Friedel–Crafts Acylation In Friedel–Crafts acylation, a benzene ring is treated with an acid chloride (RCOCl) and AlCl3 to form a ketone. Ketone functional group…. C C=O C 17 Note: reaction is as if the chlorine has been substituted by the ring See previous slide 18  Intramolecular Friedel–Crafts Reactions Starting materials that contain both a benzene ring and an electrophile (A) New bond 19  Previous slides dealt with unsubstituted benzene What happens if the benzene ring has a substituent on it????? Reaction results are based on the effects of electrons and electron density as we have previously discussed…..logically work your way through the reactions Substituted benzene rings may undergo electrophilic aromatic substitution (addition of another substituent to the ring)…how does the original substituent on the ring affect the reaction? 20 Substituted benzene rings may undergo electrophilic aromatic substitution (addition of another substituent to the ring)…what does the substituent affect? 1. Affects the electron density of the ring: increases or decreases it Donation of electron density to the ring makes benzene more electron rich. Withdrawal of electron density from the ring makes benzene less electron rich. This affects the reactivity of the ring 2. Electrophilic substitution on a substituted benzene produces isomers some of which are favored over others….preferred product, etc 3. Products are formed because of Inductive Effects Resonance Effects Electron withdrawing and donating effects Basically combinations of the above All this means is that electrons move in specific ways as previously discussed 21 All this means is that electrons move in specific ways…or, the effect of the substituent on the ring will direct where the electrophile will add to the ring…because The most stable carbocation intermediate is formed (usually a combination of the effects is what occurs) 22 N, O, and X have an electron-withdrawing inductive effect. alkyl groups have an electron-donating inductive effect. Electron density is then either “increased” or “decreased” within the ring 23 Resonance effects occur with substituents containing lone pairs or pi bonds. An electron-donating resonance effect is when resonance structures place a negative charge on carbons of the benzene ring. To determine what will happen, ask: Can electrons be “pushed” into the ring…to produce a negative charge?. 24 Resonance effects occur with substituents containing lone pairs or pi bonds. an electron withdrawing resonance effect with when resonance structures place a positive charge on carbons of the benzene ring. ASK: Can electrons be “pulled” from the ring leaving a positive charge? Last 2 slides: Generally: see what can happen to the atom that is bonded to the ring…..ASK: does that affect the ring? Meaning: does the aromaticity get disrupted, then react, then reform? 25 Important…what do the last 4 slides mean? Alkyl groups donate electrons by an inductive effect no resonance effect is present because they lack nonbonded electron pairs or π bonds any alkyl-substituted benzene is more electron rich than benzene itself. all of these have “alkyl” electron donating effects 26 Important (continued): An O or N atom bonded directly to a benzene ring has a dominating resonance effect which is electron donating. an inductive withdrawing effect is present but the resonance effect is stronger 27 Important (continued): If a halogen, X, is directly bonded to a benzene ring, then the inductive effect dominates and the net effect is electron withdrawal. X = Br, Cl, F, I Note: any group with a slightly or full positive charge that is directly bonded to the ring also has an inductive effect Y+ 28 Sample problem 16.3 pg 741 29 30 Electrophilic aromatic substitution is a general reaction of all aromatic compounds A substituent affects: 1. The rate of the reaction: A substituted benzene can react faster or slower than benzene itself. 2. The orientation: The new group is located either ortho, meta, or para to the existing substituent (ex. Y on ring below can be anything). The identity of the first substituent determines the position of the second incoming substituent. Ortho is position #2 on the ring ortho Meta is #3 meta Para is #4 para ortho meta 31 Example: Toluene reacts faster than benzene in all substitution reactions. electron-donating CH3 group activates the ring to electrophilic attack. Ortho and para products predominate. Alkyl group is an ortho, para director. Remember: this is as if Br+ was added….+ charge attracted to activated ring …more electron density 32 Example: Nitrobenzene reacts more slowly than benzene in all substitution reactions. electron-withdrawing NO2 group deactivates the ring to electrophilic attack meta product predominates. NO2 group is called a meta director. 33 Continues on next page 34 Sample problem 16.4 continued 35 All substituents can be divided into three general types: Summary 36 Summary 37 Summary Note: nonbonded electrons only on O or N are activators; halogens are deactivators 38 HW (for part up to here) 16.6, 16.8, 16.15, 16.17 a, c, e 39 Note There are two general types of ortho, para directors and one general type of meta director. All ortho, para directors are R groups or have a nonbonded electron pair on the atom bonded to the benzene ring. All meta directors have a full or partial positive charge on the atom bonded to the benzene ring. 40 Directing effects of a group on the ring are determined by the stability of the carbocation that forms, after the electrophile adds to the ring, by using resonance and induction Example: how does the methyl group direct the formation of a major or preferred product in a toluene reaction with an electrophile? (which position is preferred?) 41 Toluene example continued: look at resonance and CH3 group induction effects The CH3 group directs electrophilic attack ortho and para to itself because an electron-donating inductive effect stabilizes the carbocation intermediate when the charge is on the carbon that is attached to the CH3 group. Preferred product column..not a resonance form 42 Continued on next slides with amine and nitro groups The same concepts are applied: Look at how many resonance structures can occur. More allow better stabilization Then look at the inductive effects. How do these help with increasing or decreasing stabilization Then use “logic” to determine any gain or loss of a benefit: ex. How do the apparent charges in resonance interact with each other? (see nitro group example) 43  Example: amine group, NH2 directs electrophilic attack ortho and para to itself because the carbocation intermediate has additional resonance stabilization. Preferred product column..not a resonance form 5 resonance forms 4 forms 5 forms 44 all meta directors: example nitro group, NO2: meta attack occurs because attack at the ortho and para position gives a destabilized carbocation intermediate. 45 Summary of Reactivity and Directing Effects of groups attached to the benzene ring Figure 16.8 46 47 48 49 50 Extra concerning activation reactions A catalyst is needed (FeX3 ) to add more than one halide (FeX3 ) to Benzene rings activated by strong electron-donating groups—OH, NH2, and their derivatives (OR, NHR, and NR2)….polyhalogenation Otherwise, only ortho and para products are formed by monosubstitution 51 52 Extra concerning deactivation reactions Friedel–Crafts reactions will not occur on a benzene ring deactivated by strong electron-withdrawing groups (i.e., any of the meta directors) Nor on rings with with 2 groups: AlCl3 forms a complex with the NH2 group that deactivates the ring 53 Generally; an alkyl halide and AlCl3 places an electron-donor R group on the ring which activates the ring for further reaction. Generally, further reaction after Friedel–Crafts acylation does not occur because of deactivating effects 54 Important to mention that having two substituents on a benzene ring results in each group having an influence on the effects.....(logical) This is section 16.11 (pages 752 – 754) …..will not be covered 55 So how does all this work: Order of addition in a reaction…. Directing effects are used to synthesize disubstituted benzene products….which substituent must be added first in order to get a desired product Ex. Pg 754 synthesize p-bromonitrobenzene from benzene Which substituent should be added first? Note: the substituents are in para positions; use the ability of the first substituent to add the second 56 If bromination precedes nitration, then the desired product can be synthesized 57 If nitration occurs before bromination, then the undesired meta isomer is formed 58 59 60 Remember: deactivation means loss of electron density so E+ doesn’t attack as readily 61 Nucleophilic aromatic substitution Can also occur results in the substitution of a halogen on a benzene ring by a nucleophile. Two different mechanisms are proposed to explain the result of the reaction. For our purpose, just note that it occurs and that an electron withdrawing group on the ring facilitates the reaction 62 Nucleophilic aromatic substitution example: notice that meta and para products are formed (from a para compound) so mechanism must be different than electrophilic substitution (mechanism will not be covered) 63 Rest of reactions in chapter deal with topics we have covered or can cover in other chapters in the future as needed 16.14 Halogenation of alkyl benzenes……radical chemistry Chapt 13 16.15 Oxidation and reduction….will be covered in carbonyl chemistry 64 Multistep synthesis (and retrosynthesis) will become more involved as previously discussed concepts, theories and reactions are used cumulatively to solve problems To develop a synthesis: 1. Be sure to see what the starting material is and how it differs from the product; 2. Determine each step in moving forward from the starting material or moving backward from the product. 3. Put each step together logically 4. Do not be fooled that a problem showing only the starting material and product is a “one-step” synthesis (see problem on next page as a review example) 65 66 67 68 Hw Chapter 16 Look over review pages at end of chapter pgs 767 – 771 From earlier in the chapter 16.6, 16.8, 16.15, 16.17 a, c, e 16.9 carefully look at the product; notice if the starting materials would give this product. Reaction is based on things we have already discussed in other chapters. If you can’t determine what has happened, then look at page 735 16.40 b, c; 16.45 a (what is X); 16.53 a, b; 16.54 (look at the compound carefully and think about what reaction will occur..this is a trick question by the author) 16.78 only explain what happens to pyridine (C3 is the position number) 69