Nucleophilic displacement reaction mechanisms

The first commercial PPS process by Phillips synthesized a low molecular weight linear PPS that had modest mechanical properties. It was usehil in coatings and as a feedstock for a variety of cured injection-molding resins. The Phillips process for preparing low molecular weight linear PPS consists of a series of nucleophilic displacement reactions that have differing reactivities (26). 

The photolysis of chlorinated aromatic compounds occurs by several processes which follow predictable routes 13). They frequently undergo photochemical loss of chlorine by dissociation of the excited molecule to free radicals or, alternatively, through a nucleophilic displacement reaction with a solvent or substrate molecule. Either mechanism is plausible, and the operation of one or the other may be influenced by the reaction medium and the presence of other reagents. 

It was noted in Section V,B that the chlorophenyl carbene complex 85 can be prepared by chlorine addition to carbyne complex 80. Treatment of 85 with one equivalent of PhLi does not afford 80, suggesting that the reaction sequence is reduction/substitution rather than substitution/reduc-tion. The recent report (127) of a nucleophilic displacement reaction of the molybdenum chlorocarbyne complex 87 with PhLi to generate phenylcar-byne complex 88 suggests that the intermediacy of the chlorocarbyne complex 86 in the above mechanism is not unreasonable. 

In contrast with aliphatic nucleophilic substitution, nucleophilic displacement reactions on aromatic rings are relatively slow and require activation at the point of attack by electron-withdrawing substituents or heteroatoms, in the case of heteroaromatic systems. With non-activated aromatic systems, the reaction generally involves an elimination-addition mechanism. The addition of phase-transfer catalysts generally enhances the rate of these reactions. 

The most frequently encountered reactions in organic sulfur chemistry are nucleophilic displacement reactions. The mechanism and steric course of reactions have been the main points of interest of research groups all over the world, in particular, Andersen, Cram, Johnson, and Mislow in the United States Kobayashi and Oae in Japan Kjaer in Denmark and Fava and Montanari in Italy. The results of these investigators have been discussed exhaustively in many reviews on sulfur stereochemistry. In a recent report on nucleophilic substitution at tricoordinate sulfur, the literature was covered by Tillett (10) to the end of 1975. Therefore only some representative examples of nucleophilic substitution reactions at chiral sulfur are discussed here. However, recent results obtained in the authors laboratory are included. 

The two limiting cases of nucleophilic displacement reactions are designated as SnI or Sn2 to indicate those mechanisms that respectively display overall first-order or second-order kinetics. These mechanisms are illustrated by the classical case of the reaction of hydroxide ion with chloromethane, and they differ with respect to the timing of the bond-breaking step relative to the bondmaking step. 

The A-acetyl derivatives of the 2-alkylthio-l,3-thiadiazol-4-imines (124, R = SR, R = Ac) undergo nucleophilic displacement reaction with amines (benzylamine, cyclohexylamine, morpholine, or aniline) giving the 2-amino derivatives (124, R = NRj, R = Ac). The salt (126, R = R = Ph, R = R = H, X = Cl) reacts with aniline at room temperature giving 4-anilino-2-phenyl-l,3-thiazole (128), presumably by a mechanism involving cleavage of the heterocyclic ring. ... 

Several mechanisms have been proposed for the intriguing interconversions of sulfur (or selenium) rings. These include the formation of (i) radicals by homolytic S-S bond cleavage, (ii) thiosulfoxides of the type S =S via ring contraction (an intramolecular process) or (iii) spirocyclic sulfuranes (or sele-nanes) via an intermolecular process. A fourth alternative (iv) invokes nucleophilic displacement reactions. Generic examples of mechanisms (ii)-(iv) for homoatomic sulfur or selenium rings are depicted in Scheme 12.1. 

Nucleophilicity and leaving group ability 211 Effect of solvation on the gas-phase reaction 212 Mechanism of the gas-phase SN2 reaction 213 Potential energy surfaces for gas-phase SN2 reactions 214 Recent theoretical developments 218 Some examples of gas-phase SN2 reactions involving positive ions 220 Nucleophilic displacement reactions by negative ions in carbonyl systems 222 General features 222... 

Nucleophilic displacement reactions are often competitive with other processes promoted by a nucleophile, such as addition-elimination, or proton abstraction and base-induced elimination in which the nucleophile acts as a strong base. This particular situation is especially true in reactions that also involve attack at an unsaturated carbon centre. The delicate interplay between these different mechanisms is in itself a matter of great interest, and as yet it has defied attempts to rationalize it on a quantitative basis. 

Several significant reviews have appeared in recent years which contributed greatly to current knowledge of epoxide reaction mechanisms. Among them may be cited excellent discussions by Winetein and Henderson,am Kliel, 0 and Parker and Isaacs. Older articles of an encyclopedic nature include those of Bodforss,1 Meerwein,11 and Tiffeneau.1117 The well-known review by StreifcwieeerlMa may be consulted for a broader treatment of nucleophilic displacement reactions in general. 

Reactivities comparable to allylic halides are found in the nucleophilic displacement reactions of benzylic halides by SN1 and SN2 mechanisms (Table 14-6). The ability of the benzylic halides to undergo SK1 reactions clearly is related to the stability of the resulting benzylic cations, the electrons of which are extensively delocalized. Thus, for phenylmethyl chloride,... 

In 1933 the two still widely accepted mechanisms for nucleophilic displacement reactions were proposed by Hughes, Ingold, and Patel.4 They found that decomposition of quartenary ammonium salts, R4N+Y, to give R3N and RY exhibited two different kinds of kinetic behavior depending on the ammonium salt used. For example, when methyl alcohol was formed from trimethyl-n-decylammonium hydroxide (Equation 4.3), the rate of formation of methyl alcohol was found to be second-order, first-order each in trimethyl-n-decylam-monium cation and in hydroxide ion as in Equation 4.4. On the other hand, the rate of formation of diphenylmethanol from benzhydryltrimethylammonium... 

The mechanism for the nucleophilic displacement reaction of benzyl chloride with potassium cyanide has also been studied under multiphasic conditions, i.e., an scC02 phase and a solid salt phase with a tetraheptylammonium salt as the phase-transfer catalyst (PTC) (Scheme 3.8). The kinetic data and catalyst solubility measurements indicate that the reaction pathway involves a catalyst-rich third phase on the surface of solid salt phase. 

Allylic halides and tosylates show enhanced reactivity toward nucleophilic displacement reactions by the Sn2 mechanism. For example, allyl bromide reacts with nucleophiles by the SN2 mechanism about 40 times faster than n-propyl bromide. 

As in benzenoid chemistry, some nucleophilic displacement reactions can be copper catalyzed. Illustrative of these reactions is the displacement of bromide from 3-bromothiophene-2-carboxylic acid and 3-bromothiophene-4-carboxylic acid by active methylene compounds (e.g., AcCH2C02Et) in the presence of copper and sodium ethoxide (Scheme 136). Analogously, 2-methoxythiophene can be prepared in 83% yield by refluxing 2-bromothiophene in methanol containing excess sodium methoxide, along with copper(I) bromide as catalyst. For the analogous preparation of 3-methoxythiophene, addition of a polar cosolvent (e.g., l-methyl-2-pyrrolidone) is beneficial. In the case of halothiophenes, an SrnI mechanism is involved. 

One of the oldest techniques for overcoming these problems is the use of biphasic water/organic solvent systems using phase-transfer methods. In 1951, Jarrouse found that the reaction of water-soluble sodium cyanide with water-insoluble, but organic solvent-soluble 1-chlorooctane is dramatically enhanced by adding a catalytic amount of tetra-n-butylammonium chloride [878], This technique was further developed by Makosza et al. [879], Starks et al. [880], and others, and has become known as liquid-liquid phase-transfer catalysis (PTC) for reviews, see references [656-658, 879-882], The mechanism of this method is shown in Fig. 5-18 for the nucleophilic displacement reaction of a haloalkane with sodium cyanide in the presence of a quaternary ammonium chloride as FT catalyst. 

Nucleophilic substitution reactions. The view that substitution or displacement reactions that involve hydroxide ion are examples of polar-group-transfer reactions (with a single-electron shift) is probably the least iconoclastic proposal. Most accept the view that many nucleophilic displacement reactions occur by a SET mechanism.22 In a number of cases free-radical intermediates have been identified, which is consistent with a discrete SET step. Only a slight extension of this concept is required to encompass all nucleophilic reactions within the categories described in Scheme 8-1. 

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