SNAr mechanism

In the previous section, we saw the three criteria that are necessary in order for an aromatic ring to undergo a nucleophilic aromatic substitution reaction. The following transformation is an example  

Let s explore some possible mechanisms for this process. It eannot be an Sn2 proeess because Sn2 processes do not readily occur at an -hybridized center  

Sn2 processes are only effective with p -hybridized centers. So our reaction cannot be an Sn2 mechanism. What about SnI That would require the loss of the leaving group first to form a 

This kind of carbocation is not stabilized by resonance. Since it is unstable, it is therefore a very high-energy intermediate. So, we don t expect the leaving to leave if it means creating an unstable intermediate. Therefore, we don t expect the mechanism to be an SnI mechanism either. 

if it s not Sn2 and its not SnL then what is it And the answer is it s a new mechanism, called SnAt. In many textbooks, it is called an addition-elimination mechanism. In the first step of the mechanism, the ring is attacked by a nucleophile, generating a resonance-stabilized intermediate, called a Meisenheimer complex  

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An alternative method of six-membered ring formation has been reported utilizing an SNAr mechanism (Equation 31) <2002J(P1)790>. Chlorine is set up to leave by the electron-withdrawing influence of a group 138. The... 

The C-F bond activations in C6F6 and related compounds with ruthenium [200, 201] and rhodium [17, 78, 201] complexes, for which an SNAr mechanism is energetically unfavorable, have been explained by SET pathways. Both SN2 [128, 129, 131, 170-174, 199, 202] and SET [130, 132, 199] mechanisms have been proposed for the reaction of Co(I) complexes with alkyl and vinyl halides. 

The reaction labelled IPSO substitution is only applicable to species like OH - and NH2" and corresponds to a special case of the SNAr mechanism. 

Step 1 of the SNAr mechanism has been studied for the reaction between picryl chloride (as well as other substrates) and OH ions (3-1), and spectral evidence has been reported15 for two intermediates, one a ir complex (p. 505), and the other a radical ion-radical pair ... 

The fact that the order of halide reactivity is Br > I > Cl > F (when the reaction is performed with KNHi in liquid NH3) shows that the SNAr mechanism is not operating here.31... 

There is no clear-cut proof that a one-step Sn2 mechanism, so important at a saturated carbon, ever actually occurs with an aromatic substrate. The hypothetical aromatic Sn2 process is sometimes called the one-stage mechanism to distinguish it from the two-stage SNAr mechanism. Some of the reactions in this chapter operate by still other mechanisms, among them an addition-elimination mechanism (see 3-17). 

TABLE 13.1 Groups listed in approximate descending order of activating ability in the SNAr mechanism ... 

The reaction with ammonia or amines, which undoubtedly proceeds by the SNAr mechanism, is catalyzed by copper8" and nickel105 salts, though these are normally used only with rather unreactive halides.106 This reaction, with phase transfer catalysis, has been used to synthesize triarylamines.107 Copper ion catalysts (especially cuprous oxide or iodide) also permit the Gabriel synthesis (0-58) to be applied to aromatic substrates. Aryl bromides or iodides are refluxed with potassium phthalimide and Cu 0 or Cul in dimethylacetamide to give N-aryl phthalimides, which can be hydrolyzed to primary aryl amines.108... 

The neat resin preparation for PPS is quite complicated, despite the fact that the overall polymerization reaction appears to be simple. Several commercial PPS polymerization processes that feature some steps in common have been described (1,2). At least three different mechanisms have been published in an attempt to describe the basic reaction of a sodium sulfide equivalent anddichlorobenzene these are S Ar (13,16,19), radical cation (20,21), and Bunnett s (22) S l radical anion (23—25) mechanisms. The benzyne mechanism was ruled out (16) based on the observation that the para-substitution pattern of the monomer, j -dichlorobenzene, is retained in the repeating unit of the polymer. Demonstration that the step-growth polymerization of sodium sulfide and A dichlorobenzene proceeds via the SNAr mechanism is fairly recent (1991) (26). Further complexity in the polymerization is the incorporation of comonomers that alter the polymer structure, thereby modifying the properties of the polymer. Additionally, post-polymerization treatments can be utilized, which modify the properties of the polymer. Preparation of the neat resin is an area of significant latitude and extreme importance for the end user. 

Chloropenlafluorobenzene 5 is reduced with lithium aluminum hydride to give a mixture of five products, in three of which a C-F bond is predominantly hydrogenolyzed as a consequence of the SNAr mechanism.62... 

Relation to Nucleophilic Aromatic Substitution by the SNAr Mechanism... 

The SnAR mechanism is an addition-elimination mechanism that proceeds through a carbanion with delocalized electrons (a Meisenheimer complex). The following steps show the mechanism for the formation of p-nitrophenol from p-nitroiodobenzene. 

The most important experimental data about NMR, IR, and UV spectroscopy have been reported in CHEC-I. In addition, an AMI SCF-MO study has been published <88JOC3900>. The relaxed reaction profile for aromatic nucleophilic substitution of some chloropyrimido[4,5-J]pyridazine has been investigated using the MNDO procedure <90JST(63)45>. Kinetic measurements and MNDO calculations show that the C-8 position of the pyridazine ring is more reactive than C-5 in nucleophilic substitution reactions, and these follow a two-step SNAr mechanism <89T4485>. 

Chromium tricarbonyl-complexed aryl fluorides undergo nucleophilic substitution reactions. The substitution is not a straightforward SNAr mechanism as can be seen using, for example, 4-methoxy-l-fluorobenzene complex (71). Reaction of (71) with acetylide (72) gives a 1 2 mixture of the 1,2 and 1,3 products (73) and (74) (Scheme 115). Other leaving groups include halogens, alkoxides, and amines. Indazoles can be prepared by reaction with hydrazine followed by acidic deprotection-decomplexation (Scheme 116). 

The reaction between aryl halides and cuprous cyanide is called the Rosenmund-von Braun reaction Reactivity is in the order I > Br > Cl > F, indicating that the SNAr mechanism does not apply. Other cyanides (e.g., KCN and NaCN) do not react with aryl halides, even activated ones. This reaction has been done in ionic liquids using CuCN. ° The reaction has also been done in water using CuCN, a phase transfer catalyst, and microwave irradiation. 

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