Nucleophilic substitution reactions features

The term nucleophilicity refers to the effect of a Lewis base on the rate of a nucleophilic substitution reaction and may be contrasted with basicity, which is defined in terms of the position of an equilibrium reaction with a proton or some other acid. Nucleophilicity is used to describe trends in the kinetic aspects of substitution reactions. The relative nucleophilicity of a given species may be different toward various reactants, and it has not been possible to devise an absolute scale of nucleophilicity. We need to gain some impression of the structural features that govern nucleophilicity and to understand the relationship between nucleophilicity and basicity. ... 

Compound 40 has not yet been synthesized. However, there is a large body of synthetic data for nucleophilic substitution reactions with derivatives of 41 [synthesized from aliphatic and aromatic aldehydes, pyridine, and trimethylsilyl triflate (92S577)]. All of these experimental results reveal that the exclusive preference of pathway b is the most important feature of 41 (and also presumably of 40). 

The synthesis of nitro dyes is relatively simple, a feature which accounts to a certain extent for their low cost. The synthesis, illustrated in Scheme 6.5 for compounds 140 and 141, generally involves a nucleophilic substitution reaction between an aromatic amine and a chloronitroaromatic compound. The synthesis of C. I. Disperse Yellow 14 (140) involves the reaction of aniline with l-chloro-2,4-dinitroaniline while compound 141 is prepared by reacting aniline (2 mol) with compound 144 (1 mol). 

Ionisation of the hydroxy groups in cellulose is essential for the nucleophilic substitution reaction to take place. At neutral pH virtually no nucleophilic ionised groups are present and dye-fibre reaction does not occur. When satisfactory exhaustion of the reactive dye has taken place, alkali is added to raise the pH to 10-11, causing adequate ionisation of the cellulose hydroxy groups. The attacking nucleophile ( X ) can be either a cellulosate anion or a hydroxide ion (Scheme 7.8), the former resulting in fixation to the fibre and the latter in hydrolysis of the reactive dye. The fact that the cellulosic substrate competes effectively with water for the reactive dye can be attributed to three features of the reactive dye/ cellulosic fibre system ... 

B. Some Kinetic Features of Aromatic Nucleophilic Substitution Reactions... 

When nucleophilic substitution reactions are attempted, the expected product may often be accompanied by one or more additional products that arise from competing reactions. Since these competing reactions share features of the nucleophilic substitution mechanism, they are readily rationalized. 

When the attacking atom of the nucleophile carries a leaving group, replacement of hydrogen can take place via the VNS (vicarious nucleophilic substitution) reaction,15 as shown in Scheme 3.16 The key feature of this reaction is the rate-limiting base-induced 3-elimination from the cr-adduct. 

Unlike the nucleophilic substitution reactions which generate stable onium halide after the reaction, nucleophilic additions to electrophilic C=X double bonds (X=C, N, O) provide rather basic onium anion species as an initial product. If the anion is sufficiently stable under the reaction conditions, onium anion will then exchange the counter ion for the other metal carbanion at the interface to regenerate the reactive onium carbanion Q+R. In another scenario, the basic onium anion may abstract the acidic hydrogen atom of the other substrate to provide Q 1 R directly. Such a reaction system ideally requires only a catalytic amount of the base although, in general, a substoichiometric or excess amount of the base is used to lead the reaction to completion. An additional feature of this system is the substantial possibility of a retro-process at the crucial asymmetric induction step, which might be problematic in some cases. 

The reaction of XIII with EtOH in CHjCl EtOH, in 1 1 molar ratio, affords the ethoxy-derivative, [8,8-(q2-dppp)-9-(OEt)-nido-RhSB,H,] (XIV) behavior which is seen in the series of related compounds.12,111 This suggests that the boron vertex at the 9-position in Xm, and the related series of compounds, is prone to nucleophilic substitution reactions. XIV was characterized by NMR spectroscopy, mass spectrometry and X-ray diffraction. In contrast to the parent rhodathiaborane IV, and XIII, compound XIV does not feature fluxional behavior, even at 373 K implying, perhaps, AG values greater than 64 kjmol 1 for a possible dynamic process in XIV. The apparent large difference in the activation energy for the substituted versus the unsubstituted species may be due to either electronic or steric effects. The differences in the structures of XIII and XIV are minimal except for the B(9)-B(10) distances which differ by 0.083 A.4b This tends to suggest a role for this bond in the fluxional process although a purely steric influence of the substituent at the 9-position in XIV cannot be ruled out. 

There are a number of synthetically important applications, involving these heterocycles, as unstable intermediates, which are reviewed here. These applications feature the ability of selenium to be readily extruded from seleniranes and selenirenes, neighboring group participation by / -Se to control the stereochemistry of nucleophilic substitution reactions, and facile, chemoselective replacement of Se by H in radical-induced reactions. 

When a substituent with a good leaving ability is present in the 1,2,4-triazine ring at C-3, C-5, and/or C-6, nucleophilic substitution reactions can occur. Many SN reactions are described in the literature. In Sections IV,A-C, examples of displacement of one, two, and three nucleofugic groups are discussed. In this article, the displacement reactions are not exhaustingly reviewed. We show only the fundamental reaction features, their value, and scope for application in the synthesis of functionalized 1,2,4-triazine derivatives. As far as the mechanisms of nucleophilic sub-... 

Similar reactivity studies have been conducted with nucleophilic substitution reactions both at the furan nucleus and at side-chain groupings,374" 375,419,422 t e on y additional feature being the formation of Meisenheimer complexes in reactions with nitrofurans.456,4563... 

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. 

Several natural products, for example siderophores, contain the N-hydroxy amide Y[CON(OH)] motif [138], Within a peptide backbone, this group increases the stability to enzyme degradation and induces characteristic conformational behavior [139]. In addition to the synthesis in solution of N-hydroxy amide-containing peptides (which is not trivial), a new solid-phase approach has recently been developed [140]. To explore the features of the N-hydroxy amide moiety using automated and combinatorial techniques, a method for the preparation of v /[CON(OH)] peptide ligands for MHC-I molecules has been elaborated [140], The strategy for the parallel preparation of these peptidomimetics on a solid support is illustrated in Scheme 7.9. The key step is the nucleophilic substitution reaction of resin-bound bromocarboxylic acids by O-benzylhydroxylamine, which requires several days. 

Sulfonate esters are especially useful reactants in nucleophilic substitution reactions in synthesis. They have a high level of reactivity and can be prepared from alcohols by reactions that do not directly involve the carbon atom at which substi-mtion is to be effected. The latter feature is particularly important in cases where the stereochemical and structural integrity of the reactant must be maintained. Trifluo-romethanesulfonate (triflate) ion is an exceptionally reactive leaving group and can... 

Although the pJCa is 3.2, HCOOH has an interesting feature. The yield of 104a is seemingly low, however, a large quantity of 104a is present as its 1-formyl derivative (104b). Consequently, the nucleophilic substitution reaction of 52 is attained most successfully with HCOOH (entry 3). 

Why are thioesters superior to ordinary esters as acyl-transfer agents Part of the answer lies in the acidity difference between alcohols and thiols (Sec. 7.1 7). Since thiols are much stronger acids than are alcohols, their conjugate bases, SR, are much weaker bases than OR. Thus, the —SR group of thioesters is a much better leaving group, in nucleophilic substitution reactions, than is the —OR group of ordinary esters. Thioesters are not so reactive that they hydrolyze in cellular fluid, but they are appreciably more reactive than simple esters. Nature makes use of this feature. 

The reactivity of these complexes will not be discussed individually, but rather the various features of the nucleophilic substitution reaction will be outlined and the complexes behaviour will be compared and contrasted in this respect. 

---