Aliphatic bimolecular nucleophilic

The C-X bond of alkyl halides and sulfonate esters is polarized such that the carbon has a positive dipole. Halides and sulfonate anions are good leaving groups. Nucleophiles attack primary and secondary alkyl halides, displacing the leaving group in what is known as aliphatic, bimolecular nucleophilic substitution, the Sn2 reaction. The 8 2 reaction follows second-order kinetics, has a transition state rather than an intermediate, and proceeds via back-side attack of the nucleophile on the halide and inversion of configuration. 

The Sn2 reaction involves the attack of a nucleophile from the side opposite the leaving group and proceeds with exclusive inversion of configuration in a concerted manner. In contrast to the popular bimolecular nucleophilic substitution at the aliphatic carbon atom, the SN2 reaction at the vinylic carbon atom has been considered to be a high-energy pathway. Textbooks of organic chemistry reject this mechanism on steric grounds [175]. 

The reactions presented thus far are examples of nucleophilic aliphatic substitution reactions, in which a nucleophile substitutes for a leaving group at an aliphatic carbon. Nucleophilic aliphatic substitution proceeds with backside attack and inversion of configuration in a bimolecular process. In other words, the nucleophile collides with the electrophilic carbon atom to initiate the reaction. A shorthand symbol is used to describe this reaction Sjfl, where S means substitution, N means nucleophile, and 2 means bimolecular, or nucleophilic bimolecular substitution. Once a reaction is identified as Sn2, back-side... 

K. Okamoto, S. Fukui, I. Nitta, and H. Shingu, Bull. Chem. Soc. Jpn., 40, 2354 (1967). Kinetic Studies of Bimolecular Nucleophilic Substitution. VIll. The Effect of Hydroxylic Solvents on the Nucleophilicity of Aliphatic Amines in the Menschutkin Reaction. 

Tables IV through IX summarize the data that are currently available on the rates of bimolecular substitution and dehydrohalogenation reactions between sulfur nucleophiles and halogenated aliphatic substrates in aqueous solution (i.e., either measured in water or extrapolated to water from a non-aqueous or partially aqueous solvent). The sulfrir nucleophiles considered in these tables are HS-, S2-, S42-, S52- (Table IV), S2032 (Tables V and VIII), SO32-, HSO3 (Table VI), thiolate anions (Tables VII, VIII, and IX), thiols, thioethers, and thioadds (Table VII).

Over the past ten years, absolute rate data have been reported on the kinetics of several bimolecular silene reactions in solution, including both head-to-tail and head-to-head dimerization the [l,2]-addition reactions of nucleophilic reagents such as water, aliphatic alcohols, alkoxysilanes, carboxylic acids and amines and the ene-addition, [2 + 2]-cycloaddition and/or [4 + 2]-cycloaddition of ketones, aldehydes, esters, alkenes, dienes and oxygen. The normal outcomes of these reactions are summarized in Scheme 1. 

In contrast to esterification, etherification is carried out in an alkaline medium and the etherifying agents are alkyl halides. The general reaction is termed aliphatic nucleophilic substitution and, employed under normal conditions, is of the bimolecular type. 

Kinetic studies of the nucleophilic reactions of azolides have demonstrated that the aminolyses and alcoholyses proceed via a bimolecular addition-elimination reaction mechanism, as does the neutral hydrolysis of azolides of aromatic carboxylic acids. Aliphatic carboxylic acid azolides which are subject to steric hindrance can be hydrolyzed in aqueous medium by an 5n1 process. There have been many studies of these reactions, and evidence supporting both 5n1 and 5n2 processes leaves the impression that there are features of individual olysis reactions which favour either an initial ionization or a bimolecular process involving a tetrahedral intermediate (80AHC(27)241, B-76MI40701). 

For the bimolecular reaction with Ac cleavage, two reasonable mechanisms have been suggested. The first is a direct displacement analogous to the 8 2 mechanism of aliphatic nucleophilic substitution. This route is shown in Eq. (4) structure 2 is the transition state (I), although it is oversimplified because... 

The mechanisms that occur in aliphatic electrophilic substitution reactions are less well defined than those that occur in aliphatic nucleophilic substitution and aromatic electrophilic reactions. There is still, however, the usual division between unimolecular and bimolecular pathways the former consisting of only the SE1 mechanism, while the latter consists of the SE2 (front), SE2 (back) and the SEi mechanism. 

Another attempt to use the host-guest complexation of simple cyclophanes has been reported by Schneider They take the easily accessible host 7, an analogue of which had been demonstrated by Koga to bind aromatic guest molecules by inclusion into its molecular cavity, and study its rate effects on nucleophilic aliphatic substitutions of ambident anions (NOf, CN, SCN ) on 2-bromomethylnaphthalene 8 and benzylbromide. Similar bimolecular reactions are well known in cyclodextrin chemistry and other artificial host systems . In addition to the rather poor accelerations observed (see Table 3) the product ratio is changed in the case of nitrite favouring attack of the ambident nucleophile via its nitrogen atom. 

Elimination reactions to produce alkenes may compete in reactions in which nucleophilic aliphatic substitution is the desired process. Unimolecular elimination reactions, El, compete with substitutions, and bimolecular elimination processes, E2 (E stands for elimination and 2 for bimolecular), compete with S[ j2 transformations. These competitions are shown in Equations 14.6 and 14.7. The nature of El reactions is discussed in detail in Section 10.3 and that of E2 processes in Section 10.2. 

Studies have shown that the HDN of 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline catalyzed by sulfided NiMo/Al203 occur via a nucleophilic substitution mechanism [121]. On the other hand, HDN of aliphatic amines with the same catalyst—N1M0/AI2O3—occurs by -elimination [117]. The nature of the base and the amine structure dictate whether the elimination will proceed via a monomolecular (El) or a bimolecular (E2) mechanism. Similarly, for HDN reactions that occur via nucleophilic substitution, these same factors determine if the reaction will follow a monomolecular (Sn 1) or a bimolecular (Sn2) mechanism. 

When Bunnett and Zahler [1] published their landmark review in 1951, only two mechanisms of nucleophilic aromatic substitution were known. These were the unimolecular S l process, typically observed with arenediazonium salts, as in Scheme 6.1, and the bimolecular S,.jAr pathway, which is shown in Scheme 6.2 involving substitution of a halide ion by an anionic nucleophile and involving an anionic intermediate (1). As in aliphatic substitutions, both unimolecular and bimolecular pathways are possible. 

Self-Assessment Exercises 79a. Nucleophilic substitution corresponds to a substitution (either Sxjl or S[.j2) for aliphatic compounds. Electrophilic aromatic substitution is typical for aromatic compounds (an atom is replaced by an electrophile) 79b. An addition reaction is the opposite of an elimination reaction. In an addition reaction, two or more atoms (molecules) combine to form a larger one. 79c. S[,jl reaction involves the formation of carbocation. Sf.j2 reaction, on the other hand, is a one-step process in which bond breaking and bond making occur simultaneously at a carbon atom with a suitable leaving group. 79d. El reactions are unimolecular elimination reactions that proceed via carbocation intermediates. E2 reactions are bimolecular, one-step reactions that require an antiperiplanar conformation at the time of rr-bond formation and /3-bond breaking and do not involve carbocations. 

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