高等有机化学(第13至第14章)2008

高等有机化学(第13至第14章)

CHAPTER 13 Aromatic Nucleophilic Substitution

It must pointed out that nucleophilic substitutions proceed so slowly at an aromatic carbon that the reactions of Chapter 8 are not feasible for aromatic substrates. There are, however, exceptions to this statement, and it is these exceptions that form the subject of this chapter.

Reactions that are successful at an aromatic substrate are largely of four kinds:1. reactions activated by electron-withdrawing groups ortho and para to the leaving group; 2. reactions catalyzed by very strong bases and proceeding through aryne intermediates; 3. reactions initiated by electron donors; 4. reactions in which the nitrogen of a diazonium salt is replaced by a nucleophile.

MECHANISMSThere are four principal mechanisms for aromatic nucleophilic substitution.1. The SNAr Mechanism 2. The SN1 Mechanism 3. The Benzyne Mechanism 4. The SRN1 Mechanism

It is noted that solvent effects can be important

1. The SNAr Mechanism

Evidence for The SNAr MechanismThere is a great deal of evidence for the mechanism, we shall discuss only some of it. e.g.:

have been isolatedIntermediates of this type are stable salts, called Meisenheimer or Meisenheimer–Jackson salts and many more have been isolated. The structures of several of these intermediates have been proved by NMR and by X-ray crystallography.

高等有机化学(第13至第14章)

The break of the Ar-X was not the rate-determining stepThe following reaction indicated that Ar-X bond is not broken until after the rate-determining step.

Element effect of leaving groupAn increase in the electronegativity of X causes a decrease in the electron density at the site of attack attack, resulting in a faster attack by a nucleophile. When X=F, the relative rate was 3300 (compared with I=1). The very fact that fluoro is the best leaving group among the halogens in most romatic nucleophilic substitutions is good evidence that the mechanism is different from the SN1.

When X was Cl, Br, I, SOPh, SO2Ph, or p-nitrophenoxy, the rates differed only by a factor of 5. This behavior would not be expected in a reaction in which the Ar–X bond is broken in the rate-determining step. We do not expect the rates to be identical, because the nature of X affects the rate at which Y attacks.

The SN1 MechanismFor aryl halides and sulfonates, even active ones, a unimolecular SN1 mechanism is very rare; it has only been observed for aryl triflates in which both ortho positions contain bulky groups (tert-butyl or SiR3). It is in reactions with diazonium salts that this mechanism is important.

The evidence for the SN1 mechanismIn the following reaction, there are follwing evidence

1. The reaction rate is first order in diazonium salt and independent of the concentration of Y. 2. When high concentrations of halide salts are added, the product is an aryl halide but the rate is independent of the concentration of the added salts. 3. The effects of ring substituents on the rate are consistent with a unimolecular rate-determin

ing cleavage.

4. When reactions were run with substrate deuterated in the ortho position, isotope effects of~1.22 were obtained. It is difficult to account for such high secondary isotope effects in any other way except that an incipient phenyl cation is stabilized by hyperconjugation, which is reduced when hydrogen is replaced by deuterium.

高等有机化学(第13至第14章)

5. That the first step is reversible cleavage was demonstrated by the observation that when Ar15N≡N was the reaction species, recorvered starting material contained not only Ar15N≡N, but also ArN≡15N. This could arise only If the nitrogen breaks away from the ring and then returns. Additional evidence was obtained by treating PhN≡15N with unlabeled N2 at various pressures. At 300 atm, the recovered product had lost 3% of the labeled nitrogen, indicating that PhN2+ was exchanging with atmospheric N2.

There is kinetic and other evidence that step 1 is more complicated and involves two steps, both reversible:

Intermediate[Ar+N2], which is probably some kind of a tight ion–molecule pair, has been trapped with carbon monoxide.

The Benzyne MechanismThe incoming group does not always take the position acated by the leaving group (most interesting of all). Some aromatic nucleophilic substitutions are clearly ifferent in character from those that occur by the SNAr mechanism (or the SN1 mechanism). These substitutions occur on aryl halides that have no ctivating groups; Bases are required that are stronger than those normally used; 50% 50% e.g.: the reaction of 1-14C-chlorobenzene with potassium amide:

Mechanism

Other evidence1. If the aryl halide contains two ortho substituents, the reaction should not be able to occur. 2. It had been known many years earlier that aromatic nucleophilic substitution occasionally results in substitution at a different position.This is called cine substitution and can be illustrated by the conversion of o-bromoanisole to m-aminoanisole. In this particular case, only the meta isomer is formed.

3. The fact that the order of halide reactivity is Br> I> Cl> F (when the reaction is performed with KNH2 in liquid NH3) shows that the SNAr mechanism is not operating here.

高等有机化学(第13至第14章)

Fact:Me Me I Me NH2-

The SRN1 MechanismH2N Me Me Me+ H2N Me Me Me

Reaction condition: Strong base Result: 1. cine substitution along with normal substitution 2. The ratio of A and B was not the same 3. If C …… 此处隐藏：49052字，全部文档内容请下载后查看。喜欢就下载吧 ……