Nucleophilic substitution exothermic

It is reported that an industrial explosion was initiated by charging potassium hydroxide in place of potassium carbonate to the chloro-nitro compound in the sulfoxide [1], Dry potassium carbonate is a useful base for nucleophilic displacement of chlorine in such systems, reaction being controlled by addition of the nucleophile. The carbonate is not soluble in DMSO and possesses no significant nucleophilic activity itself. Hydroxides have, to create phenoxide salts as the first product. These are better nucleophiles than their progenitor, and also base-destabilised nitro compounds. Result heat and probable loss of control. As it nears its boiling point DMSO also becomes susceptible to exothermic breakdown, initially to methanethiol and formaldehyde. Methanethiolate is an even better nucleophile than a phenoxide and also a fairly proficient reducer of nitro-groups, while formaldehyde condenses with phenols under base catalysis in a reaction which has itself caused many an industrial runaway and explosion. There is thus a choice of routes to disaster. Industrial scale nucleophilic substitution on chloro-nitroaromatics has previously demonstrated considerable hazard in presence of water or hydroxide, even in solvents not themselves prone to exothermic decomposition [2],... 

For thermoneutral identity reactions, there is no thermochemical driving force. In the case of non-identity nucleophilic substitution reactions - when the nucleophile and nucleofuge are different - reaction exothermicity may be taken quantitatively into account. This can be quite elegantly considered by applying the simple Marcus equation [104-109]. For cationic reactions, where interactions with the neutral nucleophile and nucleofuge are quite weak,... 

A theoretical study of nucleophilic substitution of halophosphines by halide anions indicates the involvement of an anionic tetra-coordinated intermediate species (X-PH2-Y) , rather than a transition state structure. The authors predict that this intermediate should be detectable, and that the Sn2 reaction at trivalent phosphorus is exothermic when the reactant halide anion is more electronegative... 

By far the most important type of reaction displayed by halophosphines is nucleophilic substitution. This is pivotal to the preparation of many other three-coordinate compounds containing either solely P—C, P—O, P—N bonds, or mixed combinations. These reactions are often exothermic and frequently carried out at low temperatures. For the synthesis of phosphorus(III) compounds containing a P—O or P—N bond it is often necessary to add a base (triethylamine or pyridine are frequently used) to capture the hydrogen halide eliminated from these condensation reactions. In the case of P—C bond formation, a variety of routes are possible using various carbon-derived nucleophiles. 

Macallum reported that polymers prepared in this manner generally contained more than one sulfur atom per repeat unit (x in the range 1.0-1.3) (2). In addition the polymerization reaction was highly exothermic and difficult to control even on a small scale (3). Later Lenz and co-workers at Dow reported another synthesis of PPS (4,5,6) based on a nucleophilic substitution reaction involving the self-condensation of materials such as copper p-bromothiophenoxide. The reaction was carried out at 200-250°C under nitrogen in the solid state or in the presence of a reaction medium such as pyridine. It was quite difficult to remove the by-product, copper bromide, from polymers made by this process (7). These and other methods of polymerization have been reviewed by Smith (8). Polyphenylene sulfide resins have been described more recently by Short and Hill (9). 

Stabilization of the ionic tetrahedral intermediates manifests the specific acid (XXXIIb) and base (XXXIIc) catalysis of the nucleophilic substitution reactions. Energetically favorable proves to be a two-step formation of the tetrahedral intermediate with prior protonation of the substrate (specific acid catalysis) or deprotonation of the nucleophilic reactant (specific base catalysis). The chief factor which helps to overcome the repulsion potential and provides for the exothermicity of the formation of the intermediates XXXIIb, XXXIIc is the drawing together of the levels of the frontier orbitals of reactants and the effective mechanism of charge transfer (Fig. 5.5). 

Ethylene oxide is a very reactive substance It reacts rapidly and exothermically with anionic nucleophiles to yield 2 substituted derivatives of ethanol by cleaving the car bon-oxygen bond of the nng... 

In 2,4-disubstituted quinazolines, the 4-position reacts fastest with nucleophiles, generally even when the 4-substituent is a poorer leaving group. 2,4-Dichloroquinazoline undergoes mono-substitution at the 4-position with alcoholic alkoxides (25°, 2 hr, 80-98% yield), phenolic phenoxide (20°, 16 hr, 50% yield), aqueous hydroxide (30°, 3 hr), alcoholic methylmercaptide (20°, exothermically), alkylamines (20°, 10-60 min, 100%... 

Because the addition steps are generally fast and consequently exothermic chain steps, their transition states should occur early on the reaction coordinate and therefore resemble the starting alkene. This was recently confirmed by ab initio calculations for the attack at ethylene by methyl radicals and fluorene atoms. The relative stability of the adduct radicals therefore should have little influence on reacti-vity 2 ). The analysis of reactivity and regioselectivity for radical addition reactions, however, is even more complex, because polar effects seem to have an important influence. It has been known for some time that electronegative radicals X-prefer to react with ordinary alkenes while nucleophilic alkyl or acyl radicals rather attack electron deficient olefins e.g., cyano or carbonyl substituted olefins The best known example for this behavior is copolymerization This view was supported by different MO-calculation procedures and in particular by the successful FMO-treatment of the regioselectivity and relative reactivity of additions of radicals to a series of alkenes An excellent review of most of the more recent experimental data and their interpretation was published recently by Tedder and... 

The intrinsic stability of the aromatic n system has two major consequences for the course of reactions involving it directly. First, the aromatic ring is less susceptible to electrophilic, nucleophilic, and free-radical attack compared to molecules containing acyclic conjugated n systems. Thus, reaction conditions are usually more severe than would normally be required for parallel reactions of simple olefins. Second, there is a propensity to eject a substituent from the tetrahedral center of the intermediate in such a way as to reestablish the neutral (An + 2)-electron system. Thus, the reaction is two step, an endothermic first step resulting in a four-coordinate carbon atom and an exothermic second step, mechanistically the reverse of the first, in which a group is ejected. The dominant course is therefore a substitution reaction rather than an addition. 

Acid derivatives differ greatly in their reactivity toward nucleophilic acyl substitution. For example, acetyl chloride reacts with water in a violently exothermic reaction, while acetamide is stable in boiling water. Acetamide is hydrolyzed only by boiling it in strong acid or base for several hours. 

First consider the base-catalyzed transesterification of ethyl benzoate with methanol. This is a classic example of nucleophilic acyl substitution by the addition-elimination mechanism. Methoxide ion is sufficiently nucleophilic to attack the ester carbonyl group. Ethoxide ion serves as a leaving group in a strongly exothermic second step. 

The degree of substitution is determined by reaction temperature [7]. The first substituent is introduced in an exothermic reaction at 0°C, the second at 40-45°C and complete substitution required temperatures of 80-100°C. Tertiary amines were employed as base in order to remove hydrochloric acid liberated during the reaction. More satisfactory results (i.e., reaction time and yield) were obtained by employing a two-fold mole increase of amine-nucleophile, thereby obtaining products 7 to 12 as clear, viscous and distillable liquids in yields greater than 90 %. 

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