Nucleophiles mechanisms

Thioesters undergo the same kinds of reactions as esters and by similar mechanisms Nucleophilic acyl substitution of a thioester gives a thiol along with the product of acyl transfer For example... 

Both in the laboratory and in living organisms, the reactions of carbonyl compounds take place by one of four general mechanisms nucleophilic addition, nucleophilic acyl substitution, alpha substitution, and carbonyl condensation. These... 

The reactivity of these metal hydride-metal carbonyl reactions can be correlated with the nature of the reactants in a manner consistent with the proposed mechanism nucleophilic attack by hydride on coordinated CO. Thus reactions involving the highly nucleophilic group IV hydride, Cp gZrHg, are much faster than those of group V metal hydrides. On the other hand, the relatively electrophilic neutral binary metal carbonyls all react with Cp2NbH under mild conditions (20-50° C), whereas more electron-rich complexes such as cyclopentadienylmetal carbonyls (Cp2NbH(C0), CpV(CO) ) or anionic carbonyls (V(CO)g ) show no reaction under these conditions. 

In an extensive review on abiotic catalysis, Huang (2000) noted that the reactivity of hydrolyzable organic contaminants arises from the presence of electron-deficient (electrophilic) sites within the molecules. Figures 14.2 and 14.3 show the patterns of reactivity in two cases of nucleophihc substitution and monomolecular nucleophilic substitution. The Sj 2 mechanism (nucleophilic substitution) involves attack of the electrophilic sites by OH" or H O, generation of a higher coordination nnmber intermediate, subsequent elimination of the leaving group, and the formation of an hydrolysis product (Fig. 14.2). 

Fig. 14.2 Illustration of the mechanism (nucleophilic substitution) for hydrolysis reaction. (Huang 2000)...

A water-soluble Cj-symmetrical trisadduct of Cjq showed excellent radical scavenging properties in vitro and in vivo and exhibits remarkable neuro-pro tective properties [7,8]. It is a drug candidate for the prevention of ALS and Parldnsoris disease. Concerning the reaction mechanism, nucleophilic additions and radical additions are closely related and in some cases it is difficult to decide which mechanism actually operates [92]. For example, the first step in the reaction of f-eo with amines is a single electron transfer (SET) from the amine to the fullerene. The resulting amines are finally formed via a complex sequence of radical recombinations, deprotonations and redox reactions [36]. 

Nucleophilic displacement of a leaving group by an AE mechanism Nucleophilic displacement of a leaving group in an alkoxyazolium salt by an AE mechanism is exemplified in Scheme 11. 

The photostimulated reactions of thiolate anions with 2-halo-2 -nitropropane derivatives yield both oc-nitrosulphides via an S l pathway and disulphides (equation 71a)282 284. In contrast with the case of the oxidative dimerisation products of the mono-enolates, the disulphides are formed via an ionic mechanism nucleophilic attack by the thiolate anion on the a-halogen and subsequent reaction of a second thiolate with the sulphenyl halide. As expected for such a process, disulphide formation is favoured (and thus a-nitrosulphide formation is disfavoured) the more nucleophilic the thiolate (i.e. derived from a less acidic thiol) and the easier the abstraction of the halo-substituent (i.e. I > Br > Cl). Use of the protic solvent methanol instead of the usual dipolar aprotic solvents for the reaction of equation 71a is detrimental to the yield of the S l substitution products exclusively disulphides are formed285 (equation 71b). Methanol solvation probably retards the dissociation of the radical anion intermediate in the SRN reaction, into radical and anion, and hence retards the chain reaction relative to the ionic reaction. The non-nucleophilic methylsulphinate ion gives only an S l reaction product with 2-bromo-2-nitropropane286. 

Dichotomy of mechanisms. Nucleophilic displacement of an - or -halogen atom by the classical Sae mechanism of nucleophilic displacement via a Meisenheimer intermediate (e.g., 917) is facilitated by mesomeric stabilization of the transition state. However, the mechanistic balance is fine whereas 4-bromopyridine A-oxidc reacts with potassium amide by the AE mechanism, the 2-bromo analogue prefers the EA route. Again, nucleophilic displacement in chloropyrazines can involve the ANRORC mechanism. 

In contrast to the above intramolecular reactions, Yamamoto and coworkers have demonstrated that aromatic halo-ketones having an alkyl substituent at their a-position are transformed to cyclized products at the carbonyl carbon (Eq. 21) [60]. This suggests that a new mechanism, nucleophilic addition of the arylpalladium moiety in the key intermediate to the carbonyl group (Scheme 2), can occur. Addition of an alcohol such as 1-hexanol is essential for the reaction. A possible role of it might be to facilitate the reduction of Pd(II) to Pd(0). 

These observations are easily explained by another simple reaction mechanism, nucleophilic substitution of an alkoxide on silicon (12). In this case, the basic alkoxide oxygens tend to repel the nucleophile, OH, and the bulkier alkyl groups tend to crowd it. Therefore, more highly hydrolyzed silicons are more prone to attack. Because this mechanism would have a pentacoordinated silicon atom in the activated complex, hydrolysis of a polymer would be more sterically hindered than hydrolysis of a monomer. Reesterification would be much more difficult in alkaline solution than in acidic solution, because silanols are more acidic than the hydroxyl protons of alcohols and would be deprotonated and negatively charged at a pH lower than the point at which the nucleophile concentration becomes significant (ii). Thus, although hydrolysis in alkaline solution is slow, it still tends to be complete and irreversible, if extensive polymerization does not occur first. 

In this mechanism nucleophilic attack precedes protonation. This process occurs with strong neutral or negatively charged nucleophiles. 

Q> j Mechanism 22.1 General Mechanism—Nucleophilic Acyl Substitution... 

Nucleophilic ring opening of epoxides with heteroatom nucleophiles is another valuable method for the synthesis of many heteroatom-modified carbohydrate derivatives. The cyclic nature of epoxides renders the competing elimination process stereoelectronically unfavorable. Analogous to the above-discussed Sn2 nucleophilic mechanism, nucleophiles can open epoxide rings, and give rise to Walden inversion at the attacked carbon, furnishing a-hydroxy derivatives as illustrated in O Scheme 10. 

Most reactions of carbonyl groups occur by one of four general mechanisms nucleophilic addition, nucleophilic acyl substitution, alpha substitution, am carbonyl condensation. These mechanisms have many variations, just a alkene electrophilic addition reactions and 8 2 reactions do, but the varia tions are much easier to learn when the fundamental features of the mechanisms are understood. Let s see what the four mechanisms are and what kinds of chemistry carbonyl groups undergo. 

This simple observation has led to a reassessment of the chemistry of those rate and equilibrium processes which involve anions in solution (Parker, 1962, 1965a, 1965b). Comparison of rates of 8 2 reactions in protic and in dipolar aprotic solvents produce some new conclusions about reaction mechanisms, nucleophilic tendencies, leaving group tendencies, steric effects, salt effects, and solvent affects. This article discusses several comparisons of this type. 

The mechanism classification and the overall transformation classification are orthogonal to each other. For example, substitution reactions can occur by a polar acidic, polar basic, free-radical, pericyclic, or metal-catalyzed mechanism, and a reaction under polar basic conditions can produce an addition, a substitution, an elimination, or a rearrangement. Both classification schemes are important for determining the mechanism of a reaction, because knowing the class of mechanism and the overall transformation rales out certain mechanisms and suggests others. For example, under basic conditions, aromatic substitution reactions take place by one of three mechanisms nucleophilic addition-elimination, elimination-addition, or SrnL If you know the class of the overall transformation and the class of mechanism, your choices are narrowed considerably. 

C. Reaction Mechanisms — Nucleophilic displacements and addition, nucleophilic aromatic substitution, electrophilic additions, electrophilic aromatic substitutions, eliminations, Diels-Alder and other cycloadditions... 

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