Sn2 reaction of alkyl halides

In general, Sn2 reactions of alkyl halides show the following dependence of rate on structure ... 

Summary Sn2 Reactions of Alkyl Halides 234 6-10 Factors Affecting Sn2 Reactions Strength of the Nucleophile 236 Summary Trends in Nucleophilicity 237 6-11 Reactivity of the Substrate in Sn2 Reactions 240 6-12 Stereochemistry of the S j2 Reaction 244... 

Purpose. The conditions under which ethers are prepared are explored by the weU-known V lliamson ether synthesis.You will prepare alkyl aryl ethers by Sn2 reactions of alkyl halides with substituted phenoxide anions. The use of phase-transfer catalysis is demonstrated. 

Rearrangements, when they do occur, are taken as evidence for carbocation intermediates and point to the SnI mechanism as the reaction pathway. Rearrangements are never observed in Sn2 reactions of alkyl halides. 

Nitriles can be prepared from an Sn2 reaction of alkyl halide with cyanide ion. Because a nitrile can be hydrolyzed to a carboxylic acid, you now know how to convert an alkyl halide into a carboxylic acid. Notice that the carboxylic acid has one more carbon than the alkyl halide. 

Preparation of nitriles (Section 20.7) (a) Sn2 reaction of alkyl halides... 

The electronic structure of the transition state complex of a given reaction is, of course, unique for that reaction. Within a given reaction series, however, there will be various stereo-electronic features common to each of the transition states which themselves characterize individual processes in the reaction series. Thus, for example, all Sn2 reactions of alkyl halides have similarities in the geometrical disposition of nucleophile, the electron deficient centre, and 64... 

The mechanisms by which sulfonate esters undergo nucleophilic substitution are the sfflne as those of alkyl halides. Inversion of configuration is observed in Sn2 reactions of alkyl sulfonates and predominant inversion accompanied by racernization in SnI processes. 

Amines can be prepared by means of Sn2 reactions involving alkyl halides and nitrogen nucleophiles. 

Table 6.4 Relative Rates of Reactions of Alkyl Halides in SN2 Reactions... 

Sn2 substitution reactions of alkyl halides with hard nucleophiles such as alkyl anions can be achieved most readily with the aid of organocopper chemistry [95]. Sn2 reactions with epoxides and aziridines are also synthetically useful [96]. The... 

It has been suggested that the reaction of alkyl halides is not purely of the electron transfer type and may include some Sn2 component, particularly where the... 

Table 135 Calculated Concentration of Nucleophile Required to Compete with Water in an SN2 Reaction with Alkyl Halides Assuming an s Value of 1...

Ammonia and amines can function as nucleophiles in SN2 displacement reactions of alkyl halides (Section 8-7E). Such processes provide syntheses of alkanamines only with those halides that are reactive in SN2 but not E2 reactions. For example,... 

The preparation of nitriles by SN2 reactions between alkyl halides and cyanide ion has been mentioned previously (Section 8-7F) and this is the... 

The term stereoselective is often confused with the term stereospecific, and the literature abounds with views as to the most satisfactory definition. To offer some clarification, it is perhaps timely to recall a frequently used term, introduced a decade or so ago, namely the stereoelectronic requirements of a reaction. All concerted reactions (i.e. those taking place in a synchronised process of bond breaking and bond forming) are considered to have precise spatial requirements with regard to the orientation of the reactant and reagent. Common examples are SN2 displacement reactions (e.g. Section 5.10.4, p. 659), E2 anti) elimination reactions of alkyl halides (e.g. Section 5.2.1, p.488), syn (pyrolytic) elimination reactions (Section 5.2.1, p.489), trans and cis additions to alkenes (e.g. Section 5.4.5, p. 547), and many rearrangement reactions. In the case of chiral or geometric reactants, the stereoisomeric nature of the product is entirely dependent on the unique stereoelectronic requirement of the reaction such reactions are stereospecific. 

For synthesis of an unsymmetrical ether, the most hindered alkoxide should be reacted with the simplest alkyl halide rather than the other way round (Following fig.). As this is an SN2 reaction, primary alkyl halides react better then secondary or tertiary alkyl halides. 

Because of the contribution of structures such as the one on the right to the resonance hybrid, the a-carbon of an enamine is nucleophilic. However, an enamine is a much weaker nucleophile than an enolate anion. For it to react in the SN2 reaction, the alkyl halide electrophile must be very reactive (see Table 8.1). An enamine can also be used as a nucleophile in substitution reactions with acyl chlorides. The reactive electrophiles commonly used in reactions with enamines are ... 

Mechanism 6-1 Allylic Bromination 228 Summary Methods for Preparing Alkyl Halides 229 6-7 Reactions of Alkyl Halides Substitution and Elimination 231 6-8 Second-Order Nucleophilic Substitution The Sn2 Reaction 232 Key Mechanism 6-2 The S j2 Reaction 233 6-9 Generality of the SN2 Reaction 234... 

These reactions consist of two steps. The first is the formation of a stabilized anion—usually (but not always) an enolate—by deprotonation with base. The second is a substitution reaction attack of the nucleophilic anion on an electrophilic alkyl halide. All the factors controlling SnI and Sn2 reactions, which we discussed at length in Chapter 17, are applicable here, step l formation of enolate anion step 2 alkylation (SN2 reaction with alkyl halide)... 

The synthetic utility of alkylation of enolates is utilized in the syntheses of malonic ester (3.3) and acetoacetic ester (3.2). For example, carbanion generated from malonic ester undergoes an Sn2 reaction with alkyl halide to yield alkyl-substituted malonic ester. The monosubstituted malonic ester still has an active hydrogen atom. The second alkyl group (same or different) can be introduced in a similar manner. Acid-catalyzed hydrolysis or base-catalyzed hydrolysis of mono- or disubstituted derivative of malonic ester followed by acidification gives the corresponding mono- or disubstituted malonic acid, which on decarboxylation yields the corresponding monocarboxylic acid (Scheme 3.3). 

In contrast to the behavior of the foregoing nickel(I) complexes as catalysts, the catalytic reactions of alkyl halides with cobalt(I) species such as vitamin Bi2s, cobaloximes(I), and cobalt(I) salen exhibit a significant difference. Cobalt(I) species, acting as potent nucleophiles in Sn2 reactions with alkyl halides, give stable alkylcobalt(III) intermediates. Lexa and coworkers [318] have discussed this mechanistic scheme for the catalytic reduction of l-bromobutane by the electrogenerated cobalt(I) tetraphenylpor-phin complex, where TPP denotes the ligand. Reversible one-electron reduction of the parent cobalt(II) species... 

Thiolate anions make excellent nucleophiles in Sn2 reactions on alkyl halides. It is enough to combine the thiol, sodium hydroxide, and the alkyl halide to get a good yield of the sulfide. 

In summary, while alkyl sulfonates react exclusively by the 5N2-like mechanism of Scheme 2 (or equation 4), evidence for alternative SET processes in reactions of both alkyl iodides and alkyl bromides has recently accumulated. The relative contributions of Sn2 and SET mechanisms in reactions of alkyl halides is difficult to quantify, however, since the normal substitution product can arguably arise via either pathway. 

The order of reactivity of aryl halides is Ar T Ar CI Ar-Br Ar I. which is the reverse order for SN2/SN1 reactions of alkyl halides (see Section 5.3.1). As fluorine is the most electronegative halogen atom, it strongly polarises the C—F bond. This makes the carbon 8+, and hence it is susceptible to nucleophilic attack. The fluorine atom is also small, and hence the incoming nucleophile can easily approach the adjacent carbon atom (as there is little steric hindrance). 

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