Exothermicity, nucleophilicity

When the hydroxide is hydrated with a water molecule, the displacement channel is unchanged but the proton-transfer channel is reduced by one order of magnitude (Figure 3b compared with Figure 3a). Hydration suppresses the competition of endothermic proton transfer with exothermic nucleophilic displacement (Figure 5). These two results—a competition that is contrary to the thermodynamics and the suppression of this competition by one water of hydration—are summarized in Figure 5 and have been explained in terms of the relative energies of the reaction intermediates (24). 

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... 

The reactions are highly exothermic. Under Uquid-phase conditions at about 200°C, the overall heat of reaction is —83.7 to —104.6 kJ/mol (—20 to —25 kcal/mol) ethylene oxide reacting (324). The opening of the oxide ring is considered to occur by an ionic mechanism with a nucleophilic attack on one of the epoxide carbon atoms (325). Both acidic and basic catalysts accelerate the reactions, as does elevated temperature. The reaction kinetics and product distribution have been studied by a number of workers (326,327). 

Simple alkyl radicals such as methyl are considered to be nonnucleophilic. Methyl radicals are somewhat more reactive toward alkenes bearing electron-withdrawing substituents than towards those with electron-releasing substituents. However, much of this effect can be attributed to the stabilizing effect that these substiments have on the product radical. There is a strong correlation of reaction rate with the overall exothermicity of the reaction. Hydroxymethyl and 2-hydroxy-2-propyl radicals show nucleophilic character. The hydroxymethyl radical shows a slightly enhanced reactivity toward acrylonitrile and acrolein, but a sharply decreased reactivity toward ethyl vinyl ether. Table 12.9 gives some of the reactivity data. 

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%... 

The CO-X bond breaking is the result of an electrophilic attack (on the carbonyl oxygen atom, hence the catalytic role of acids in these rupture reactions) or a nucleophilic one (on the carbonyl carbon atom whose positive property is due to the X electron-withdrawing property). The dangers of this type of reaction come from its speed and high exothermicity and/or instability of the products obtained in some cases. The accidents that are described below can make one believe that acid anhydrides in general and acetic anhydride in particular represent greater risks than acid chlorides since they constitute the accident factor of almost all accidents described. This is obviously related to their frequent use in synthesis rather than acid chlorides, that are rarely used. 

According to B3LYP/6-31G computations of the intermediates and TSs, there are no large barriers to the reaction and it is strongly exothermic.156 Measured Ea values are around 10kcal/mol.157 The complexation of borane to the catalyst shifts electron density from nitrogen to boron and enhances the nucleophilicity of the hydride. The... 

Imidazolides of aromatic sulfonic acids react much more slowly in alcoholysis reactions than the carboxylic acid imidazolides. Although the reaction with phenols is quantitative when a melt is heated to 100 °C for several hours, with alcohols under these conditions only very slight alcoholysis is observed. In the presence of 0.05 equivalents (catalytic amount) of sodium ethoxide, imidazole sodium, of NaNH2, however, imidazolides of sulfonic acids react with alcohols almost quantitatively and exothermically at room temperature in a very short time to form sulfonic acid esters (sulfonates). (If the ratio of sulfonic acid imidazolide to alcoholate is 1 2, ethers are formed see Chapter 17). The mechanism of catalysis by base corresponds to that operative in the synthesis of carboxylic esters by the imidazolide method. Because of the more pronounced nucleophilic character of alkoxide ions, sulfonates can also be prepared in good yield by alcoholysis of their imidazolides in the presence of hydroxide ions i.e., with alcoholic sodium hydroxide. 45 Examples of syntheses of sulfonates are presented below. 

Monohomologation of the THF complex of 1-boraadamantane 42 can also be achieved with nucleophilic trimethylsulfoxonium methylide (Scheme 31) and involves a two-step process, consisting of the formation of an ate-complex 83 followed by a [l,2]-migration. Transformation of 42 into 83 is an exothermic reaction. The stmcture of 77 was confirmed by X-ray crystallography <20010L3063, 2003JA12179>. 

Addition of ammonia as a model nucleophile to nitrile oxides was studied by a semiempirical MNDO method, for fulminic acid and acetonitrile oxide (121). The reaction is exothermic and proceeds in two steps. The first (and rate-determining) step is the formation of a zwitterionic structure as intermediate. The second step, which involves transfer of a proton, is very fast and leads to the formation of Z-amidoximes in accordance with experimental data. Similar results were... 

Recently, semiempirical PM3 computational analysis (568) and first ab initio study (569) of the nucleophilic addition to chiral nitrones of Grignard reagents have been carried out. The data revealed that all reactions are exothermic and proceed through /w-complexation of nitrones with the organometalic reagent. 

The success of the present method depends critically on the initial presence of an alcohol to trap the intermediate phosphonium species.12 If the alcohol is added last, the R3P—CX4 reaction described above (an exothermic process for the more nucleophilic phosphines) may go to completion, in which case little or no alkyl halide is formed.13 Since the reaction displays several characteristics of an SN2 process, it is thought to proceed by the pathway illustrated ... 

These high energy species are extremely reactive, with themselves and with nucleophiles, and can generate runaway exotherms. With water, rapid evolution of carbon dioxide results. Some instances are reported [1], A compound of this class was resposible for the worst chemical industry accident to date. Di-isocyanates are extensively employed, with polyols, to generate polyurethane polymers. The polymerisation temperature should be held below 180°C or decomposition may occur which, in the case of foams, may induce later autoignition. 

The reaction is highly exothermic as one might expect for an oxidation reaction. The mechanism is shown in Figure 15.1. Palladium chloride is the catalyst, which occurs as the tetrachloropalladate in solution, the resting state of the catalyst. Two chloride ions are replaced by water and ethene. Then the key-step occurs, the attack of a second water molecule (or hydroxide) to the ethene molecule activated towards a nucleophilic attack by co-ordination to the electrophilic palladium ion. The nucleophilic attack of a nucleophile on an alkene coordinated to palladium is typical of Wacker type reactions. 

C1CH2CH2CHZ [Z = C(0)H, CCH, or CN] to cyclopropane derivatives. In each case the cyclization barrier is lower than the 5n2 barrier of an analogous acyclic system, despite the cyclization being over 25kcal moP less exothermic. The surprisingly small enthalpic barrier to the cyclizations is due to the nucleophile being held in close proximity to the electrophilic site in the substrate, and this destabilizes the ground state. 

The amine-catalyzed mercaptan-epoxide reaction (Equation 4) proceeds exothermally at room temperature (27. 28). The order of average relative nucleophile-displacement rates (Table II) further suggests that mercaptans react significantly faster than amines and that the addition of the mercaptlde (RS ) ion to the epoxide group is the rate determining step (30). 

Agrawal and co-workers have reported the synthesis of A,A -bis(l,2,4-triazol-3-yl)-4,4 -diamino-2,2, 3,3, 5,5, 6,6 -octanitroazobenzene (17) (BTDAONAB) via nitration-oxidative coupling of 4-chloro-3,5-dinitroaniline (152) followed by nucleophilic displacement of the chloro groups with 3-amino-1,2,4-triazole. BTDAONAB has the unique distinction of being the most thermally stable explosive reported so far (DTA exotherm 550 °C) as compared to well known thermally stable explosives such as TATB ( 360 °C), TACOT ( 410 °C), NONA ( 440 50 °C), and PYX ( 460 °C). 

IV.C.3.a), nucleophilic displacement of formate is an asynchronous process with substantial alkoxynitrenium ion character at the transition state. The reaction is computed to be exothermic by 5.0 kcalmol and to have an Ea of 4.2 kcalmol 13,157... 

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 oxidation of a heteroatom bearing a lone pair of electrons (e.g. amine, sulfide or phosphine) with increased nucleophilicity of the heteroatom typically results in an early TS, especially with phosphines. Since the N—O bond in an N-oxide is particularly weak, this can sometimes be an endothermic reaction, in contrast to the highly exothermic oxidation of a phosphine with its associated very strong P—O bond (Table 13). 

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