Nucleophilic substitution features

How can these trends be explained An important consideration is the interaction of the solvent methanol with the anionic nucleophile. We have largely ignored the solvent in our discussion of organic reactions so far, in particular, radical halogenations (Chapter 3), in which they play an insignificant role. Nucleophilic substitution features polar starting materials and a polar mechanism, and the nature of the solvent becomes more important. Let us see how the solvent can become involved. 

The points that we have emphasized in this brief overview of the S l and 8 2 mechanisms are kinetics and stereochemistry. These features of a reaction provide important evidence for ascertaining whether a particular nucleophilic substitution follows an ionization or a direct displacement pathway. There are limitations to the generalization that reactions exhibiting first-order kinetics react by the Sj l mechanism and those exhibiting second-order kinetics react by the 8 2 mechanism. Many nucleophilic substitutions are carried out under conditions in which the nucleophile is present in large excess. When this is the case, the concentration of the nucleophile is essentially constant during die reaction and the observed kinetics become pseudo-first-order. This is true, for example, when the solvent is the nucleophile (solvolysis). In this case, the kinetics of the reaction provide no evidence as to whether the 8 1 or 8 2 mechanism operates. 

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. ... 

All the reactions discussed in this review are aromatic nucleophilic substitutions in the ordinary sense. These reactions are briefiy described in the following sections with respect to their general kinetic features and mainly involve aza-activated six-membered ring systems, although a few studies of other heteroaromatic compounds are also available. 

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). 

In the skeleton of many chelating diphosphines, the phosphorus atoms bear two aryl substituents, not least because the traditional route to this class of compounds involves the nucleophilic substitution with alkali metal diarylphosphides of enantiopure ditosylates derived from optically active natural precursors, approach which is inapplicable to the preparation of P-alkylated analogs. The correct orientation of these aryl substituents in the coordination sphere has been identified as a stereo chemically important feature contributing to the recognition ability of the metal complex [11,18-20]. 

Figs. 11 and 12 show typical mo diagrams for square planar and octahedral complexes. Inspection reveals that the metal orbital (z is the axial direction) in a square planar complex is involved in the n bonding system and available for a bonding in the transition state. This is a feature shared by nucleophilic substitution at square planar complexes with the spectacularly associative nucleophilic aromatic substitutions. The octahedral complexes discussed in this chapter... 

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). 

The ability of a nitro group in the substrate to bring about electron-transfer free radical chain nucleophilic substitution (SrnI) at a saturated carbon atom is well documented.39 Such electron transfer reactions are one of the characteristic features of nitro compounds. Komblum and Russell have established the SrnI reaction independently the details of the early history have been well reviewed by them.39 The reaction of p-nitrobenzyl chloride with a salt of nitroalkane is in sharp contrast to the general behavior of the alkylation of the carbanions derived from nitroalkanes here, carbon alkylation is predominant. The carbon alkylation process proceeds via a chain reaction involving anion radicals and free radicals, as shown in Eq. 5.24 and Scheme... 

Today it is widely accepted that fivefold coordinated silicon plays a key role in the reaction mechanisms of the nucleophilic substitution having a trigonal bipyramidal transition state species which ressemble these transition states can be isolated in some special cases. The structural features fit well to kinetic data and possibly explain the significantly higher reactivity (proved by experimental data) of Si-pentacoordinated compounds compared to their tetracoordinated analoga. 

The Stille reaction featuring bromoquinoxaline 84 and vinylstannane delivered vinylquinoxaline 85. In addition, 85 was further manipulated to a 5-aminomethylquinoxaline-2,3-dione 86 as an AMPA receptor antagonist [47]. Pd-catalyzed nucleophilic substitution on the benzene ring has also been described [48]. Thus, transformation of 5,8-diiodoquinoxalines to quinoxaline-5,8-dimalononitriles with sodium malononitrile was promoted by PdCl2,(Ph3P)2. 

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... 

Reaction mechanisms divide the transformations between organic molecules into classes that can be understood by well-defined concepts. Thus, for example, the SnI or Sn2 nucleophilic substitutions are examples of organic reaction mechanisms. Each mechanism is characterized by transition states and intermediates that are passed over while the reaction proceeds. It defines the kinetic, stereochemical, and product features of the reaction. Reaction mechanisms are thus extremely important to optimize the respective conversion for conditions, selectivity, or yields of desired products. 

For the nucleophilic substitution of Scheme 4.15, the following features have been established ... 

Unlike conventional nucleophilic substitution, the cyclopropane ring does not cleave during SbmI reactions of Schemes 7.64 and 7.65. Another common feature of these two reactions consists... 

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. 

The essential feature of enamines is that they are nitrogen analogues of enols and behave as enolate anions. They effectively mask a carbonyl function while activating the compound towards nucleophilic substitution. 

An intriguing feature is that the previously unknown bisindoles 154 display atropisomerism as a result of the rotation barrier about the bonds to the quaternary carbon center. With the use of A-triflyl phosphoramide (1 )-41 (5 mol%, R = 9-phenanthryl), bisindole 154a could be obtained in 62% ee. Based on their experimental results, the authors invoke a Brpnsted acid-catalyzed enantioselective, nucleophilic substitution following the 1,2-addition to rationalize the formation of the bisindoles 154 (Scheme 65). 

The parent polymer by itself is not a useful material owing to the extreme hydrolytic sensitivity of the P-Cl bond. However, this feature has been turned around and used as an advantage. Nucleophilic substitution of the chlorines in the polymer results in substituted polyphosphazenes which are hydrolytically stable. Also, using this method the polymer architecture and properties are readily fine-tuned by a subtle variation of the substituent. Over three hundred types of polyphosphazenes have been synthesised by this method. Assembly of organic polymers containing cyclo-phosphazenes as pendant groups is another approach that is gaining importance [6]. 

One of the factors directing the alkylation of an enolate is the Jt-facial selectivity. The differences in reactivity of the two diastereotopic faces of the enolate, due to steric and electronic features, contribute to the steric control of the alkylation (for extensive reviews, see refs 1, 4, and 30). Likewise, stereoelectronic features are important control elements for C- versus O-alkylation, as illustrated by the cyclization of enolates 1 and 3 via intramolecular nucleophilic substitution 39. 

The essential features of the mechanism for aliphatic nucleophilic substitution at tertiary carbon were established in studies by Hughes and Ingold." ° However, as chemists probed more deeply, the problems associated with the characterization of borderline reaction mechanisms were encountered, and controversy remains to this day about whether these problems have been entirely solved." What is generally accepted is that ferf-butyl derivatives undergo borderline solvolysis reactions through a ferf-butyl carbocation intermediate that is too unstable to diffuse freely through nucleophilic solvents such as methanol and water. The borderline nature of substitution reactions at tertiary carbon is exemplihed by the following observations. 

If L = halogen, this type of reaction is referred to as dehydrohalogenation. Thus, when assessing the fate of halogenated compounds in natural waters, this process has to be considered in addition to nucleophilic substitution. The question then is what structural features and environmental conditions determine whether only one or both of these two competing types of reactions will be important. 

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