Nucleophilic aromatic kinetic

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 treatise on kinetics is a logical and fitting medium in which to analyze and discuss just such limitations and uncertainties of mechanism. The present chapter will attempt such a treatment for the SN2 mechanism in nucleophilic aromatic substitution. An effort will be made to pinpoint every assumption and highlight every instance where alternate choices are possible. The end result hoped for is a clearer delineation of the known and the probable from the uncertain and the unknown. 

Since chlorine is always in more than a hundred-fold excess compared to bromine the reaction is occurring by pseudo monomolecular kinetics. The reaction occurs via nucleophilic aromatic substitution by an addition-elimination mechanism, the so-called SjsfAr mechanism (ref. 24). 

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 . 

Some theoretical aspects of thiophene reactivity and structure have also been discussed, for example the kinetics of proton transfer from 2,3-dihydrobenzo[6]thiophenc-2-onc <06JOC8203>, the configuration of imines derived from thiophenecarbaldehydes <06JOC7165>, and the relative stability of benzo[c]thiophene <06T12204>. The kinetics of nucleophilic aromatic substitution of some 2-substituted-5-nitrothiophenes in room temperature ionic liquids have also been investigated <06JOC5144>. 

The thermal decomposition of arenediazonium tetrafluoroborates is slowed down when the salt is complexed by 18-crown-6 (Bartsch et al., 1976). The kinetic data obtained for the 4-t-butylbenzenediazonium salt at 50°C in 1,2-dichloroethane revealed that the rate of complexed to uncomplexed salt is more than 100. Other crown ethers such as dibenzo-18-crown-6 and dicyclohexyl-18-crown-6 exhibited the same effect but smaller molecules such as 15-crown-5 did not influence the rate at all. It is not only the rate of the Schiemann reaction that is affected by the crown ether nucleophilic aromatic substitutions by halide ions (Cl-, Br-) at the 4-positions in arenediazonium salts are retarded or even entirely inhibited when 18-crown-6 is added. This is attributed to the attenuation of the positive charge at the diazonio group in the complex (Gokel et al., 1977). 

The usual kinetic law for S/v Ar reactions is the second-order kinetic law, as required for a bimolecular process. This is generally the case where anionic or neutral nucleophiles react in usual polar solvents (methanol, DMSO, formamide and so on). When nucleophilic aromatic substitutions between nitrohalogenobenzenes (mainly 2,4-dinitrohalogenobenzenes) and neutral nucleophiles (amines) are carried out in poorly polar solvents (benzene, hexane, carbon tetrachloride etc.) anomalous kinetic behaviour may be observed263. Under pseudo-monomolecular experimental conditions (in the presence of large excess of nucleophile with respect to the substrate) each run follows a first-order kinetic law, but the rate constants (kQbs in s 1 ruol 1 dm3) were not independent of the initial concentration value of the used amine. In apolar solvents the most usual kinetic feature is the increase of the kabs value on increasing the [amine]o values [amine]o indicates the initial concentration value of the amine. 

The Excited State From Which the Nucleophilic Aromatic Photosubstitution Starts. Kinetics. 236... 

THE EXCITED STATES FROM WHICH THE NUCLEOPHILIC AROMATIC PHOTOSUBSTITUTION STARTS. KINETICS... 

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],... 

Dziomko and coworkers have utilized the nucleophilic aromatic substitution of aryl amines to chloropyrazoles or chloropyridines in the template step of their macrocycle syntheses.174 175 The nature of the template process is unclear and it could simply be thermodynamic. However, a kinetic effect is a distinct possibility and would require attack of a coordinated aryl amine (Scheme 52). 

It is of interest to observe that the kinetic behaviour (and the effect of changes of temperature on the rate of reactions) of brominations of olefins and of electrophilic aromatic brominations confirms the presence of pre-associative processes77,130,131 on the reaction pathway, as well as that observed for some nucleophilic aromatic substitutions132. 

We include in Sections I,A and I,B some general features of the Tsuji-Trost reaction with comments on kinetic versus thermodynamic control in allylations and in alkylations in general. Then we review in Sections II, III, and IV all cases known to the authors of the application of the Tsuji-Trost reaction to ambident nucleophilic aromatic heterocycles. This leaves out of the review the allylation of such heterocyclic ambident nucleophiles as 2-piperidone and the like. By aromatic, we mean any heterocycle for which a tautomeric or mesomeric formula can be written that is aromatic in the normal structural sense of having 4n + 2n- electrons cyclically conjugated. 

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. 

It is noteworthy that - in principle - other cyclization products can also result from the diketone 129. Evidently, conjugation to the aromatic ring stabilized the enolate formed by deprotonation of the acetyl side chain at C-1 of 129 in such a way that this anion reacted as the nucleophile in kinetically controlled aldol reactions. 

Self-association of anilines was suggested to be responsible for several anomalous kinetic behaviours in nucleophilic aromatic substitution reactions in apolar aprotic solvents40, but this conclusion was questioned41. 

Nuclear kinetic energy, 217 Nucleophilic aromatic substitutions. 474-76... 

Mancini PME, Fortunato G, Adam C, Terenzani A, Vottero LR (2002) Specific tmd nonspecific solvent effects on aromatic nucleophilic substitutions. Kinetics of the reaction of 1-fluoro-2,6-dinitrobenzene and homopiperidine in binary solvent mixtures. J Phys Oig Chem 15 258-269... 

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