Chapter 16 - ELECTROPHILIC ATTACK ON DERIVATIVES OF BENZENE...

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Unformatted text preview: ELECTROPHILIC ATTACK ON DERIVATIVES OF BENZENE DERIVATIVES R E+ ? What arethee cts of thesubstitue ffe nt? What a. Re activity of thebe nering nze b. b. Re gioche istry of EAS ortho, m ta, para m : e Re Aspirin is a disubstitute be ne d nze : Aspirin Donors and Acceptors Donors Donors Donors activate activate Acceptors Acceptors deactivate deactivate Activators: Send electrophile to the ortho and para ortho para positions positions Deactivators: Send electrophile to the meta meta positions positions Reminder: NO2 CH3 < < Increasing rate of EAS Induction and Resonance Induction Both can ope , not always in thesam dire rate e ction I nductivee ct: ffe Occurs -Occurs through theσ fram work e f ram - Tape off rapidly with rs distance -Gove d by rne e ctrone le gativity of atom s and re sulting polarization of bonds bonds Re sonancee ct: Wins out ove inductivee ct ffe r ffe whe in com tition. n pe whe -Take placethrough π s -Take bonds -Longe range r -Longe -S trong in charge d syste s m Electrostatic Potentials Benzene Methylbenzene Benzenamine (Toluene) (Aniline) Nitrobenzene A. Induction A. 1. Donors: R = alkyl, activateby hype rconjugation, 1. alkyl hype ortho/para dire cting Faste than r be ne nze No furthe brom r ination, be causeBr de activate s S ere am sults with HNO3, S 3, Frie l-C O Frie de rafts re nts: Mainly age ortho and para substitution (le ortho, be ss causeof ste rics). Why ortho-para ? Me chanism : Me Steric effect larger with large alkyl group: tert-Bu gives only para Steric tert 2. Acce ptors: R = -C , -C l , -C FC (OR) , de activateby 2. -C de e ctrone le gativity, m ta dire e cting S r than lowe be ne nze Frie l-C de rafts re nts too slow, only strong E+ work. Why m ta? age Frie Why e Me chanism : Me Wins by de fault: Le bad option ast B. Resonance B. O 2 1. Donors: R = -NH , -NR’R”, -NHC -OR, R’, 1. -NH activateby re sonating lonepairs, ortho/para-dire cting, do not ne d e activate re ortho/para-dire do catalyst in haloge nation catalyst Why ortho/para? Re Why ortho/para? sonance> induction Me chanism : Me Octe t!! Octe t!! EAS 2 NH O 2. Acce ptors: R = C OOH, C NO ,S H, R, O H, 2. C N, de activateby re sonance m ta-dire ,e cting re Frie l-C de rafts re nts too slow. Why m ta? age Why e Me chanism : Me EAS 2H CO 3. Exce ption: R = X (haloge , de n) activate(slightly) by (haloge e ctrone le gativity, iinductive> re nductive sonance but ne rthe ss , ve le ortho/para-dire cting! ortho/para-dire Why? Re sonance> inductivein charge inte e d rm diate . Re Me chanism : Me Octe t!! Octe t!! Summary of Substituent Effects Summary Summary of Relative Rates Summary Disubstituted BenzenesDisubstituted Higher Substitution R' R" R' R' R" R" S ubstitue Effe areAdditive nt cts The Strongest Activator Wins GUIDELINE 1. Them powe activator controls t heposition of attack ost rful GUIDELINE 2. Thre classe of substitue in theorde of dim e s nts r dim inishing control whe in n Thre com tition: pe 2 1. Re sonanceactivators arebe NR , OR; st NR 2. Haloge X and inductiveactivators, such as R ns 2. 3. De O F 3. activators C R < C < NO Whe the is com tition f or re le n re com pe giose ctivity be e m m rs twe n e be of thesam group, difficult to pre (unle the both point to e dict ss y sam thesam position): Ne d to look up table e s. t he e 6 5 6 GUIDELINE 3. Whe product m n ixture arepre d on thebasis of s dicte guide s 1 and 2, products fromortho attack to line bulky groups or be e two substitue aredisfavore (dashe line twe n nts d d s): S rics! te GUIDELINE 4. Guide s 1 through 3 apply to e n m highly substitute be ne Note line ve ore d nze s. : Highe substitution in thestarting m rial re s thenum r of possible r ate duce be products: I .e lifege e r....... ., ts asie Proble : m F3 C OCH 3 H N O3 , H 2 S O 4 ? C( CH 3 )3 Answe r: S tronge activator wins st N O2 F3 C OCH 3 F3 C OCH 3 H N O3 , H 2 SO4 Hinde d re C( CH 3 )3 Hinde d re C( CH 3 )3 Strategies in EAS We can change the sense of the directing power of substituents Re duction Re 1. -NO2 1. -NO (m ta dire e ctor) Oxidation -NH2 (ortho/para dire ctor) Re duction: Zn(Hg), HC or H2, Ni; or Fe HC l; ,l O Oxidation: C 3 C F OOH Exam s: ple Exam Re trosynthe Think of N substitue as NO2 sis: nt O 2. –CR 2. Re duction Re Oxidation -C 2R H (ortho/para dire ctor) (m ta dire e ctor) Re ducing age : nts H2, Pd, Pd, C 3C 2OH (hydroge s carbonyl to alcohol, the cle s the H H OH nate n ave be nzylic OH) or be C m e n Re le m nse duction Zn(Hg), HC Δ l, Oxidizing age : nts C 3, H2S 4, H2O rO O Dire butylation give (1-m thylpropyl)be ne(se -butylbe ne and ove ct s e nze c nze ) ralkylation. 3. Friedel-Crafts reactions do not work with strongly deactivated benzenes with Consider making 1-(3-nitrophenyl)ethanone: 4. Use reversible sulfonation for blocking certain positions certain 5. Prote ction of NH2 and OH functions 5. and NH2 is quitebasic, inte re with e ctrophile OH is quiteacidic, rfe s le s; inte re with base (organom tallics). rfe s e inte s Prote ction De prote ction OH N aO H , C H 3I conc. HI De prote ction Prote ction OCH 3 Phe no l O Or, as above C 3C to m e r. : H Cl ake ste Methoxybenzene 6. EASin polycyclic be noids: An e rcisein nze xe re sonance . Exam : Naphthale ple ne Exam ? Them culeis activate and d The ole se ctivefor attack at C le 1: se Why? Le us look at re t sonancein there ctiveinte e spe rm diate cations: Fivere s! Activation Five sonancestructure = Activation Attack at C 1 Two re s Two sonanceform with intact be nerings nze be Thre re e s d Thre sonanceform with disrupte cyclic conjugation cyclic Attact at C 2 Attact Only onere sonanceformwith an intact be nering nze (84% ) (8% ) EAS on Substituted Naphthalenes EAS Exam : ple A. Activators: Activators: -Dire e ctrophile ct le t o thesam ring e sam -Ortho/para A. De activators: A. De -Dire e ctrophileaway (to othe ring) and to α-positions ct le r away (C and C 5 8) (C Sterics For othe be noid syste s: Always writeout thecom tese of re r nze m ple t sonance For form at all possibleuniquepositions. s f orm ...
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This note was uploaded on 11/11/2009 for the course CHEM 368537 taught by Professor Voldhart during the Spring '09 term at University of California, Berkeley.

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