SnAt mechanism

Step 1 of the SnAt mechanism has been studied for the reaction between picryl chloride (as well as other substrates) and OH ions (13-1), and spectral evidence has been reported for two intermediates, one a n complex (p. 679), 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 KNH2 in liquid NH3) shows that the SnAt mechanism is not operating here. ... 

The reaction with ammonia or amines, which undoubtedly proceeds by the SnAt mechanism, is catalyzed by copper and nickel salts, though these are normally used only with rather unreactive halides. This reaction, with phase-transfer catalysis, has been used to synthesize triarylamines. Copper ion catalysts (especially cuprous oxide or iodide) also permit the Gabriel synthesis (10-61) to be... 

The reaction between aryl halides and cuprous cyanide is called the Rosenmund-von Braun reactionP Reactivity is in the order I > Br > Cl > F, indicating that the SnAt mechanism does not apply.Other cyanides (e.g., KCN and NaCN), do not react with aryl halides, even activated ones. However, alkali cyanides do convert aryl halides to nitrilesin dipolar aprotic solvents in the presence of Pd(II) salts or copper or nickel complexes. A nickel complex also catalyzes the reaction between aryl triflates and KCN to give aryl nitriles. Aromatic ethers ArOR have been photochemically converted to ArCN. 

Analogously, the derivatization of bicyclic THD 67 with diamines, in dimethylformamide (DMF) with triethylamine as the base, via an SnAt mechanism, is possible as shown for the synthesis of compound 66 (Equation 11) <2005JOC6230, 2005JMC2266>. 

There has been a study of the mechanism of the activation of carboxylic acids to peptide formation by chloro-s -triazines in combination with tertiary amines. The first step, exemplified in Scheme 2 by the reaction of 2-chloro-4,6-disubstituted-l,3,5-triazines (18) with A -methylmorpholine, is formation of a quaternary triazinylammonium salt (20). Here there is NMR evidence for the formation at —50°C of the intermediate (19), showing that the substitution involves the two-step SnAt mechanism rather than a synchronous pathway. The subsequent reaction of (20) with a carboxylic acid yields the 2-acyloxy derivative (21), which carries an excellent leaving group for the amide-forming step. ... 

Kinetic studies of the substitution reaction of 2-chloro-l-methylpyridinium iodide with phenoxides are consistent with the SnAt mechanism, with rate-determining nucleophilic attack.38 The effects of a variety of ring substituents on the reactivities of 2-fluoro- and 2-chloro-pyridines in reactions with sodium ethoxide in ethanol have been examined. The results were discussed in terms of the combination of steric, inductive, and repulsive interactions.39 Substitution in 2,4,6-trihalopyridines normally occurs preferentially at the 4-position. However, the presence of a trialkylsilyl group at the 3-position has been shown to suppress reaction at adjacent positions, allowing substitution at the 6-position.40 Methods have been reported for the introduction and removal of fluorine atoms for polyfluoropyridines. Additional fluorine atoms were introduced by metallation, chlorination, and then fluorodechlorination, while selective removal of fluorine was achieved by reduction with either metals or complex hydrides or alternatively by substitution by hydrazine followed by dehydrogena-tion-dediazotization.41... 

SnAt mechanism. However, the 2-fluoro compound gives no product with scrambled nitrogen label, suggesting that amino product forms only by the SNAr mechanism.74)... 

The conversion of 2-chloro- to 2-aminopyrazine by amide ion in ammonia does not proceed by an SnAt mechanism. Starting material labelled at position 1 with nitro-... 

A major route to arynes and hetarynes proceeds by dehydrohalogenating molecules which are deactivated with respect to substitution by an SnAt mechanism. Frequently employed bases are amide and alkylamide ions, alkyl and aryl lithium reagents and tew-butoxide ion. In spite of various claims this approach has not been used successfully to generate a 5-membered hetaryne.68,7S)... 

FIGURE 8.3 Nucleophilic aromatic substitution (SnAt) mechanism and perfluorocarba-nions observed by NMR. 

Fitton and Rick have proposed a nonclassical SnAt mechanism for the oxidative addition of Pd(PPh3)4 to aryl halides, in which the cleavage of the C—bond in a Meisenheimer-type intermediate would be the rate-determining stepP ... 

The SNAr reactions of heteroarenes can be realized in a similar manner, as in the series of arenes [71, 82]. These nucleophilic reactions are analogous to electrochemical Sn transformations of arenes [22, 24, 25]. Terrier and co-workers considered an opportunity for electrochemical methoxylation of 4,6-dinitrobenzofuroxan by action of the methoxide ion via the SnAt mechanism [21]. The intermediate o -complex formed was oxidized successfully into the corresponding substitution product. Analogously, the formation of heteroaromatic amines has been suggested to occur via intermediacy of the corresponding amino adducts, as exemplified by the oxidation of the o -complex derived fi om the reaction of pyrimidine with NH2 (Scheme 26) [3, 102-104]. 

Now we are ready to get some practice drawing an SnAt mechanism. 

In the previous section, we discussed the three criteria that you need in order to get an SnAt mechanism. The obvious question is can it occur without all three criteria For example, what if there is no electron-withdrawing group ... 

Answer The ring does not have an electron-withdrawing group, so we are not deahng with an SnAt mechanism. Rather, we must be deahng with an elimination-addition mechanism. 

Predict the products for each of the following reactions. Just to keep you on your toes, I will throw in some problems that go through an addition-elimination mechanism (SnAt), rather than an elimination-addition. In each case, you will have to decide which mechanism is responsible for the reaction (based on whether or not you have all three criteria for an SnAt mechanism). Your products will be based on that decision. 

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