Nucleophilic polar solvent, mechanism

Primary amine-catalyzed polymerization of NCAs in various solvents revealed that certain polar solvents themselves act as catalysts [3]. Characteristic for the catalytically active solvents is a relatively high nucleophihcity [4] (see left column in Table 15.1). This observation and the formation of cyclic polypeptides from the N-substituted sarcosine-NCA evidenced that a zwitterionic polymerization mechanism was catalyzed, which involves ROP and condensation steps (see Formula 15.2). Pyridine is known for many decades to activate carboxylic anhy-drdies by charge separation, i. e., formation of carboxylate anions plus N-acyl pyridinium ions Therefore, it is obvious that pyridine catalyzes the same zwitterionic mechanism as the nucleophilic polar solvents [5]. In the case of N-un-substitued NCAs the initiation step will be again a charge separation, but instead of... 

Solvent Effects on the Rate of Substitution by the S 2 Mechanism Polar solvents are required m typical bimolecular substitutions because ionic substances such as the sodium and potassium salts cited earlier m Table 8 1 are not sufficiently soluble m nonpolar solvents to give a high enough concentration of the nucleophile to allow the reaction to occur at a rapid rate Other than the requirement that the solvent be polar enough to dis solve ionic compounds however the effect of solvent polarity on the rate of 8 2 reactions IS small What is most important is whether or not the polar solvent is protic or aprotic Water (HOH) alcohols (ROH) and carboxylic acids (RCO2H) are classified as polar protic solvents they all have OH groups that allow them to form hydrogen bonds... 

No single mechanism accounts for all the reactions. One pathway involves a concerted one-step process involving a cyclic transition state. This of necessity affords a c -product. Another possibility, more favoured in polar solvents, involves a cationic 5-coordinate intermediate [IrX(A)(CO)L2]+, which undergoes subsequent nucleophilic attack by B-. Other possibilities include a SN2 route, where the metal polarizes AB before generating the nucleophile, and radical routes. Studies are complicated by the fact that the thermodynamically more stable isolated product may not be the same as the kinetic product formed by initial addition. 

The solvent dependence of the reaction rate is also consistent with this mechanistic scheme. Comparison of the rate constants for isomerizations of PCMT in chloroform and in nitrobenzene shows a small (ca. 40%) rate enhancement in the latter solvent. Simple electrostatic theory predicts that nucleophilic substitutions in which neutral reactants are converted to ionic products should be accelerated in polar solvents (23), so that a rate increase in nitrobenzene is to be expected. In fact, this effect is often very small (24). For example, Parker and co-workers (25) report that the S 2 reaction of methyl bromide and dimethyl sulfide is accelerated by only 50% on changing the solvent from 88% (w/w) methanol-water to N,N-dimethylacetamide (DMAc) at low ionic strength this is a far greater change in solvent properties than that investigated in the present work. Thus a small, positive dependence of reaction rate on solvent polarity is implicit in the sulfonium ion mechanism. 

In other systems, similar kinetic laws were observed when studying the effect of added pyridine, although differentiation with the dimer nucleophile mechanism is made in the interpretation of the experimental results (see below). Rationalizations of the involved phenomena are based on the strong hydrogen-bond interactions between the nucleophile and the pyridine, and on the catalytic effect of a third amine molecule in the decomposition of the zwitterionic intermediate in non-polar solvents. 

Several trends emerge in these data (1) The reductive elimination of bromine is 6-13kJmol more facile than reductive elimination of chlorine in similar structures, which is consistent with weaker chalcogen-bromine bonds relative to chalcogen-chlorine bonds.(2) The reductive elimination of chlorine is accelerated by the presence of a chloride counterion as opposed to a less nucleophilic counterion such as hexafluorophosphate. (3) The rate of reductive elimination is accelerated by the presence of a more polar solvent (acetonitrile) relative to tetrachloroethane, which is consistent with development of charge in the rate-determining step. These observations suggest mechanisms for oxidative... 

In non-polar solvents many aminolysis reactions show a third-order dependence on the amine, B. This may be explained by catalysis of leaving-group departure by hydrogen-bonded homoconjugates, BH+B. Evidence for this pathway has been adduced from studies of the reactions of some nitro-activated (9-aryl oximes (7) with pyrrolidine in benzene, chlorobenzene, and dioxane, and with piperidine and hexylamine in cyclohexane. The third-order dependence on amine of the reaction of 2,6-dinitroanisole with butylamine in toluene and toluene-octanol mixtures has been interpreted in terms of a mechanism involving attack by dimers of the nucleophile. ... 

Bromo-2-methylbutane is a tertiary alkyl halide. It reacts with methanol, a weak nucleophile and polar solvent, to give an ether by an SN1 mechanism. 

The reaction involves a good nucleophile and a polar solvent (acetone). These conditions favor an Sn2 mechanism with inversion of configuration. 

The second reaction involves a weak nucleophile (CH3OH) that is also a fairly polar solvent, favoring the SN1 mechanism ... 

The exchange reaction of 1-bromonaphthalene with CuCl proceeds effectively in polar solvents, such as DMF or DMSO, at temperatures of 110-150 °C via a second-order mechanism. The reaction is reversible but the equilibrium favors formation of aryl chlorides. The catalysis is inhibited by chloride anion and by pyridine or, particularly, 2,2 -bipyri-dine. The ease of replacement decreased in the order Arl> ArBr> ArCl and the reactivity of the attacking nucleophile decreased in the order CuCl> CuBr> Cul. The exchange reac-... 

Identify the leaving group, the electrophilic carbon (the one bonded to the leaving group), the nucleophile, and the solvent (usually over the arrow). If the electrophilic carbon is methyl or a simple primary carbon, the mechanism is SN2. If the electrophilic carbon is tertiary, the mechanism is SN1. If the electrophilic carbon is secondary, allylic, or benzylic, you must examine the nucleophile and the solvent. With good nucleophiles, the mechanism is SN2. (Aprotic solvents make the nucleophile even stronger.) With poor nucleophiles and polar solvents, the mechanism is SN1. 

The leaving group (Br) is on a secondary carbon. The reaction involves a poor nucleophile (CH3OH) and a polar solvent (CH3OII), so it follows an SN1 mechanism. The initial carbocation is secondary and can rearrange to a tertiary carbocation by migration of a methyl group. 

Both of these mechanisms involve rate-determining formation of a carbocation, so they most commonly occur with tertiary (best) or secondary substrates in polar solvents. The reaction conditions are often neutral or acidic to avoid the presence of any strong base or strong nucleophile that might favor the SN2 or E2 pathways. Because the step that controls which product is formed occurs after the rate-determining step, it is much more difficult to influence the ratio of substitution to elimination here. In general, some elimination always accompanies an SN1 reaction and must be tolerated. An example is provided in the equation in Figure 9.7. 

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