Addition SnAt mechanism

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... 

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 ... 

So, 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 ... 

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. 

Chichibabin and Ziegler reaction). In the presence of good leaving groups, diazines in general are more reactive in SnAt reactions than pyridine often substitution does not occur by simple addition/elimination processes, but by ANRORC mechanisms (cf. p 418). 

The first step of the mechanism is consistent wth the addition-elimination SnAt process. The strongly nucleophilic NH2 adds to pyridine. Addition at the 2- or 4-position makes it possible for the negative charge to be shared by nitrogen and so is preferred to attack at the 3-position (Rg. 14.103). 

The mechanism is surely not an Sn2 displacement, and there is no reason to think SnAt addition—elimination is possible with an unstabilized benzene ring. This difficult mechanistic problem begins to unravel with the obsen tion by John D. Roberts (b. 1918) and his co-workers that labeled chlorobenzene produces aniline labeled equally in two positions (Fig. 14.112). 

What reactions of halides do you know besides displacement The El and E2 reactions compete with displacement reactions (Chapter 7). If HCl were lost from chlorobenzene, a cyclic alkyne, called benzyne (or dehydrobenzene), would be formed. This symmetrical bent alkyne might be reactive enough to undergo an addition reaction with the amide ion. If this were the case, the labeled material must produce two differently labeled products of addition (Fig. 14.113), because the NH2 can attack either carbon of the alkyne. This mechanism is the elimination-addition version of the SnAt reaction. 

A major study addressing the synthesis, kinetics and mechanism of SnAt displacement of 6-halopurine nucleosides with nitrogen, oxygen and sulphur nucleophiles was reported by Liu and Robins [97] (Scheme 25). The 6-fluoro group of 69 was displaced with butylamine, aniline, methanol and KSCOMe. The well understood order of reactivity at the 6-position was switched when a weakly basic aniline was used, to be I > Br > Cl> > F. An autocatalytic induction period was identified and the addition of trifluoroacetic acid eliminated this lag time and returned the reactivity order to F>other halogens. 

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