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

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Unformatted text preview: ELECTROPHILIC ATTACK ON DERIVATIVES OF BENZENE R E+ ? What arethee cts of thesubstitue ffe nt? a. Re activity of thebe nering nze b. Re gioche istry of EAS ortho, m ta, para m : e Aspirin is a disubstitute be ne d nze : Donors and Acceptors Donors activate Acce ptors de activate Activators: S nd e e ctrophileto theortho le and para positions Deactivators: S nd e e ctrophileto themeta le positions Re inde m r: NO2 CH3 < < Increasing rate of EAS Induction and Resonance Both can ope , not always in thesam dire rate e ction I nductivee ct: ffe -Occurs through the fram work e - Tape off rapidly with rs distance -Gove d by rne e ctrone le gativity of atom s and re sulting polarization of bonds Re sonancee ct: Wins out ove inductivee ct ffe r ffe whe in com tition. n pe -Take placethrough s bonds -Longe range r -S trong in charge d syste s m Electrostatic Potentials Benzene Methylbenzene Benzenamine (Toluene) (Aniline) Nitrobenzene A. Induction 1. Donors: R = alkyl, activateby hype rconjugation, 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 de rafts re nts: Mainly age ortho and para substitution (le ortho, be ss causeof ste rics). Why ortho-para ? Me chanism : Steric effect larger with large alkyl group: tert-Bu gives only para 2. Acce ptors: R = -C , -C l , -C F C (OR) , de activateby 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 e Me chanism : Wins by de fault: Le bad option ast B. Resonance O 2 1. Donors: R = -NH , -NR'R", -NHC -OR, R', activateby re sonating lonepairs, ortho/para-dire cting, do not ne d e catalyst in haloge nation Why ortho/para? Re sonance> induction Me chanism : Octe t!! Octe t!! EASNH2 NH2 O 2. Acce ptors: R = C OOH, C NO ,S H, R, O C N, de activateby re sonance m ta-dire , e cting Frie l-C de rafts re nts too slow. Why m ta? age e Me chanism : EASCO H CO2 2 3. Exce ption: R = X (haloge , de n) activate(slightly) by e ctrone le gativity, inductive> re sonance but ne rthe ss , ve le ortho/para-dire cting! Why? Re sonance> inductivein charge inte e d rm diate . Me chanism : Octe t!! Octe t!! Summary of Substituent Effects Summary of Relative Rates Disubstituted BenzenesHigher Substitution R' R" R' R' R" R" S ubstitue Effe areAdditive nt cts The Strongest Activator Wins GUIDELINE 1. Them powe activator controls theposition of attack ost rful GUIDELINE 2. Thre classe of substitue in theorde of dim e s nts r inishing control whe in n com tition: pe 2 1. Re sonanceactivators arebe NR , OR; st 2. Haloge X and inductiveactivators, such as R ns 3. De activators C R < C < NO O F Whe the is com tition for re le n re 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 thesam position): Ne d to look up table e e s. 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 HN O3 , H 2 SO 4 ? C(CH 3 )3 Answe r: S tronge activator wins st NO2 F3 C OCH 3 F3 C OCH 3 HNO3 , 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 1. -NO2 (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 Re trosynthe Think of N substitue as NO2 sis: nt O 2. CR Re duction Oxidation -C 2R H (ortho/para dire ctor) (m ta dire e ctor) Re ducing age : nts H2, Pd, C 3C 2OH (hydroge s carbonyl to alcohol, the cle s the H H nate n ave be nzylic OH) or C m e n Re le m nse duction Zn(Hg), HC l, Oxidizing age : nts C 3, H2S 4, H2O rO O Dire butylation give (1-m thylpropyl)be ne(se ct s e nze c-butylbe ne and ove nze ) ralkylation. 3. Frie l-Crafts re de actions do not work with strongly de activate be ne d nze s Consider making 1-(3-nitrophenyl)ethanone: 4. Usere rsiblesulfonation for blocking ce ve rtain positions 5. Prote ction of NH2 and OH functions NH2 is quitebasic, inte re with e ctrophile OH is quiteacidic, rfe s le s; inte re with base (organom tallics). rfe s s e Prote ction De prote ction OH NaOH, CH3I conc. HI De prote ction Prote ction OCH 3 Phenol 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 ? Them culeis activate and ole d se ctivefor attack at C le 1: Why? Le us look at re t sonancein there ctiveinte e spe rm diate cations: Fivere sonancestructure = Activation s! Attack at C 1 Two re sonanceform with intact s be nerings nze Thre re e sonanceform with disrupte s d cyclic conjugation Attact at C 2 Only onere sonanceformwith an intact be nering nze (84% ) (8% ) EAS on Substituted Naphthalenes Exam : ple A. Activators: -Dire e ctrophile ct le to thesam ring e -Ortho/para A. De activators: -Dire e ctrophileaway (to othe ring) and to -positions ct le r (C and C 5 8) Sterics For othe be noid syste s: Always writeout thecom tese of re r nze m ple t sonance form at all possibleuniquepositions. s ...
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