Polarity 358 Substitution nucleophilic bimolecular

Equation 4 can be classified as S, , ie, substitution nucleophilic bimolecular (221). The rate of the reaction is influenced by several parameters basicity of the amine, steric effects, reactivity of the alkylating agent, and solvent polarity. The reaction is often carried out in a polar solvent, eg, isopropanol, which may increase the rate of reaction and make handling of the product easier. 

Experimental data from nucleophilic substitution reactions on substrates that have optical activity (the ability to rotate plane-polarized light) shows that two general mechanisms exist for these types of reactions. The first type is called an S 2 mechanism. This mechanism follows second-order kinetics (the reaction rate depends on the concentrations of two reactants), and its intermediate contains both the substrate and the nucleophile and is therefore bimolecular. The terminology S 2 stands for substitution nucleophilic bimolecular. ... 

For secondary halides in aqueous solvents, unimolecular and bimolecular processes compete, and the result is usually a mixture of products. With strong bases and protic solvents other than water, bimolecular elimination is usually faster than substitution, although this is only an assumption and accurate predictions can be difficult with secondary substrates. In polar aprotic solvents, bimolecular processes are usually faster. If a strong base is present and a protic solvent is used, bimolecular elimination is usually preferred to bimolecular substitution, but this is another assumption. If ethanol is used as a solvent and sodium ethoxide is a nucleophilic base. Table 2.9 shows the competition between bimolecular substitution (Sn2) and bimolecular elimination (E2) for a series of alkyl bromides. The preference for E2 reactions of secondary and tertiary halides in this protic solvent is clearly shown. 

The imidazole-catalysed hydrolysis of polar substituted 2,4-dinitrophenyl acetates (21 X = Cl, OMe) has been investigated at different temperatures. The observed rates correspond to the bimolecular nucleophilic addition of the imidazole at the carboxylic carbon atom followed by a very fast hydrolysis of the (V-acetylimidazole in water. The influence of polar substituents in the acid moiety of the ester molecule on the hydrolysis reaction can be described by an electrostatic dipole-dipole interaction in the same way as the neutral hydrolysis of polar substituted ethyl acetates. By the use of both quantum and classical dynamics, a study of the neutral hydrolysis of 4-methoxyphenyl dichloroacetate (22) in water concluded that the rate-determining step is a proton transfer concerted with formation of a C-O bond. ... 

Solvent Effects on the Rate of Substitution by the S 2 Mechanism Polar solvents are required m typical bimolecular substitutions because ionic substances such as the sodium and potassium salts cited earlier m Table 8 1 are not sufficiently soluble m nonpolar solvents to give a high enough concentration of the nucleophile to allow the reaction to occur at a rapid rate Other than the requirement that the solvent be polar enough to dis solve ionic compounds however the effect of solvent polarity on the rate of 8 2 reactions IS small What is most important is whether or not the polar solvent is protic or aprotic Water (HOH) alcohols (ROH) and carboxylic acids (RCO2H) are classified as polar protic solvents they all have OH groups that allow them to form hydrogen bonds... 

The large rate enhancements observed for bimolecular- nucleophilic substitutions in polar- aprotic solvents are used to advantage in synthetic applications. An example can be seen in the preparation of alkyl cyanides (nitriles) by the reaction of sodium cyanide with alkyl halides ... 

The usual kinetic law for S/v Ar reactions is the second-order kinetic law, as required for a bimolecular process. This is generally the case where anionic or neutral nucleophiles react in usual polar solvents (methanol, DMSO, formamide and so on). When nucleophilic aromatic substitutions between nitrohalogenobenzenes (mainly 2,4-dinitrohalogenobenzenes) and neutral nucleophiles (amines) are carried out in poorly polar solvents (benzene, hexane, carbon tetrachloride etc.) anomalous kinetic behaviour may be observed263. Under pseudo-monomolecular experimental conditions (in the presence of large excess of nucleophile with respect to the substrate) each run follows a first-order kinetic law, but the rate constants (kQbs in s 1 ruol 1 dm3) were not independent of the initial concentration value of the used amine. In apolar solvents the most usual kinetic feature is the increase of the kabs value on increasing the [amine]o values [amine]o indicates the initial concentration value of the amine. 

The acylation and deacylation reactions at the serine residue can be described mechanistically as bimolecular substitutions in which a nucleophile uses an unshared electron pair to bond to a polarized carbon atom and displace the leaving group (Z) ... 

Epoxides undergo bimolecular nucleophilic displacement reactions with azide ion to produce azidoalcohols (Table 2). Azide ion preferentially attacks saturated unsymmetrical epoxides at the less substituted carbon atom in accordance with the normal pattern of polar... 

Much of the discussion which follows is related to Sjf2 reactions and more specifically to bimolecular nucleophilic substitution at a saturated carbon atom, (Ingold, 1953 Bunton, 1963). Many branches of chemistry have profited from the detailed studies made on this deceptively simple reaction (2), which has attracted the attention of physical organic chemists for many years. Especially notable contributions have been made by Hughes and Ingold (Ingold, 1953). These have led to important advances in our understanding of mechanisms, steric effects, polar substituent effects, salt effects and solvent effects. 

Apart from these inherent properties, which affect the rate of SN1 substitution, there are several external factors that may have an effect. First, it is preferable to have a weak incoming nucleophile. This is because, if it were strong, then it might attack the carbon centre that is to form the carbonium ion, and so change the mechanistic pathway from unimolecular to bimolecular. Hence, a weak nucleophile favours an SN1 substitution route, because it does not promote an SN2 route. There are, however, other important factors concerning the solvent. Suggest whether a solvent of high or low polarity would favour the SN1 reaction. 

Most of the work concerned with micellar catalysis of nucleophilic substitution refers to reactions of the Aac2 and SN2 types and will not be reviewed here. To date only a few systems have been examined in which a micellar medium affects the partitioning of solvolytic reactions between unimolecular and bimolecular mechanisms. The effects of cationic (hexadecyltrimethylammonium bromide = CTAB) and anionic (sodium lauryl sulfate = NaLS) micelles on competitive SN1 and SN2 reactions of a-phenylallyl butanoate 193) have been investigated189. The rate of formation of the phenylallyl cation 194) is retarded by both surfactants probably as a consequence of the decreased polarity of the micellar pseudo phase. The bimolec-... 

P. de la Mare, L. Fowden, E, D. Hughes, C. K. Ingold, andj. Mackie,/. Ghent. Soc., 3200 (1955). XLIX. Analysis of Steric and Polar Effects of Alkyl Groups in Bimolecular Nucleophilic Substitution, with Special Reference to Halogen Exchange. 

The possibility of rearrangement must be borne in mind particularly when considering reactions of allylic compounds. Substitution of SN1 type, which dominates in polar solvents, always leads to mixtures of isomeric rearrangement products bimolecular substitution occurs without rearrangement. Thus choice of strongly nucleophilic reactants and, particularly, repression of SN1 reaction by selection of an apolar solvent such as acetone permit reactions of allylic compounds to be undertaken without rearrangement.13... 

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