Kinetic studies nucleophilic aromatic substitution

It is regrettable that the evidence afforded by reaction kinetics is rarely, if ever, uniquely consistent with a single mechanism or a single explanation. The results for nucleophilic aromatic substitution reactions are no exception. Legitimate questions can be raised with respect to the extent to which observations made on a particular system permit generalization to other systems. Even for the specific systems studied points of detail arise, and choices have to be made where alternatives are possible. Every such choice introduces an element of uncertainty and imposes a limitation on the extent to which the reaction mechanism is, in fact, known. 

A long series of studies of aromatic nucleophilic substitution included the kinetics of reactions of l-chloro-2,4-bis(trifluoromethylsulfonyl)benzene, 3-nitro-4-chlorophenyl trifluoromethyl sulfone and 2-chlorophenyl trifluoromethyl sulfone with sodium methox-ide or ammonia in methanol . The SO2CF3 group was found to have an enormous accelerating effect, in accord with the value of 1.65, based on the dissociation of anilinium ion. Further examples of the promotion of nucleophilic aromatic substitution by fluoro-substituted sulfonyl groups are given by Yagupol skii and coworkers . 

As previously discussed, L-deprenyl (2) is a selective suicide inhibitor of MAO B. As part of a program to develop [ F]-labeled L-deprenyl for PET studies, Fowler and coworkers prepared [ C]-labeled o- and L-4-fluorodeprenyl (37) to study the effects of fluorine substitution on kinetics of uptake and localization [105]. Subsequently, no-carrier-added o,L-4-[ F]-fluoroderprenyl (38) was made by a nucleophilic aromatic substitution reaction [106],... 

The first study of a nucleophilic aromatic substitution in which formation of a Meisenheimer-type complex and its subsequent decomposition were separately observable was reported by Orvik and Bunnett (1970). The study involved the reaction of 2,4-dinitro-l-naphthyl ethyl ether [7] with n-butyl- and t-butylamine in DMSO. The use of DMSO in this kinetic study enabled the rate behaviour to be unambiguously interpreted by avoiding complications due to aggregation phenomena, while stabilizing any a-complexes which are formed. The reaction sequence is given in equation (28). In this OEt... 

The kinetics of polycondensation hy nucleophilic aromatic substitution in highly polar solvents and solvent mixtures to yield linear, high molecular weight aromatic polyethers were measured. The basic reaction studied was between a di-phenoxide salt and a dihaloaromatic compound. The role of steric and inductive effects was elucidated on the basis of the kinetics determined for model compounds. The polymerization rate of the dipotassium salt of various bis-phenols with 4,4 -dichlorodiphenylsulfone in methyl sulfoxide solvent follows second-order kinetics. The rate constant at the monomer stage was found to be greater than the rate constant at the dimer and subsequent polymerization stages. 

Abstract This chapter presents the design and analysis of the microscopic features of binary solvent systems formed by ionic liquids, particularly room temperature ionic liqnids with molecular solvents. Protic ionic liquids, ethylammonium nitrate and l-n-butyl-3-methylmidazohum (bmim)-based ILs, were selected considering the differences in their hydrogen-bond donor acidity. The molecular solvents chosen were aprotic polar (acetonitrile, dimethylsulphoxide and MA(-dimethylformide) and protic (different alcohols). The empirical solvatochromic parameters n, a and P were employed in order to analyse the behaviour of each binary solvent system. The study focuses on the identification of solvent mixtures of relevant solvating properties to propose them as new solvents . Kinetic study of aromatic nucleophilic substitution reactions carried out in this type of solvent systems is also presented. On the other hand, this is considered as a new approach on protic ionic liquids. Ethylammonium nitrate can act as both Bronsted acid and/or nucleophile. Two reactions (aromatic nucleophilic substitution and nncleophilic addition to aromatic aldehydes) were considered as model reactions. 

A detailed study of the nucleophilic aromatic substitution of hydrogen has been initiated at the Urals State Technical University (Russia) in the 1970s. In the first review on this topic, it was suggested to use the symbol Sjj in order to distinguish these reactions from the classical nucleophilic ipso-substitution Ar [8]. Later, a number of special reviews [9-38] and also the book Nucleophilic Aromatic Substitution of Hydrogen [39], which accumulated a considerable body of data on conditions, kinetics, structure of intermediates, electrochemical and mathematic modeling, as well as plausible mechanisms and the general concept of the 5 -reactions, have also been published. 

Despite both intramolecular and intermolecular mechanisms for the Chapman rearrangement having been postulated [28], it is the intramolecular one that has been confirmed by crossover experiments and isotopic labeling studies [29]. It has also been observed that the rearrangement follows first-order kinetics involving a nucleophilic aromatic substitution step [30]. 

There have been a large number of detailed studies, especially involving kinetic measurements, that have helped to establish the finer details of aromatic nucleophilic substitutions proceeding via the addition-elimination mechanism. Carbanions, alkoxides, and amines are all reactive in nucleophilic aromatic substitution and provide most of the cases in which this reaction has been used preparatively. Some examples are given in Scheme 8.8. 

Proposals for the mechanism of PPS formation include nucleophilic aromatic substitution (Sj Ar) (2radical-cation (27), and radical-anion processes (28,29). Some of the interesting features of the polymerization are that the initial reaction of the sodium sulfide-hydrate with NMP affords a soluble NaSH-sodium 4-(N-methylamino)butanoate mixture, and that polymers of higher molecular weight than pi edicted by the Caruthers equation are produced at low conversions. Mechanistic elucidation has been hampered by the harsh polymerization conditions and poor solubility of PPS in common organic solvents. A detailed mechanistic study of model compounds by Fahey provided strong evidence that the ionic S]s Ar mechanism predominates (30). Some of the evidence supporting the S s(Ar mechanism was the selective formation of phenylthiobenzenes, absence of disulfide production, kinetics behavior, the lack of influence of radical initiators and inhibitors, relative rate Hammet values, and activation parameters consistent with nucleophilic aromatic substitution. The radical-anion process was not completely discounted and may be a minor competing mechanism. 

Kinetic studies have shown that the enolate and phosphorus nucleophiles all react at about the same rate. This suggests that the only step directly involving the nucleophile (step 2 of the propagation sequence) occurs at essentially the diffusion-controlled rate so that there is little selectivity among the individual nucleophiles. The synthetic potential of the reaction lies in the fact that other substituents which activate the halide to substitution are not required in this reaction, in contrast to aromatic nucleophilic substitution which proceeds by an addition-elimination mechanism (see Seetion 10.5). 

It is quite reasonable to expect the bimolecular two-stage mechanism Sj Ar ) to predominate in most aromatic nucleophilic substitutions of activated substrates. However, only in rare instances is there adequate evidence to rule out the simultaneous occurrence or predominance of other mechanisms. The true significance of the alternative mechanisms in azines needs to be determined by trapping the intermediates or by applying modem separation and characterization methods to the identification of at least the major portion of the products, especially in kinetic studies. 

To derive the maximum amount of information about intranuclear and intemuclear activation for nucleophilic substitution of bicyclo-aromatics, the kinetic studies on quinolines and isoquinolines are related herein to those on halo-1- and -2-nitro-naphthalenes, and data on polyazanaphthalenes are compared with those on poly-nitronaphthalenes. The reactivity rules thereby deduced are based on such limited data, however, that they should be regarded as tentative and subject to confirmation or modification on the basis of further experimental study. In many cases, only a single reaction has been investigated. From the data in Tables IX to XVI, one can derive certain conclusions about the effects of the nucleophile, leaving group, other substituents, solvent, and comparison temperature, all of which are summarized at the end of this section. 

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