Nucleophiles in substitution reactions

There is little mention in the literature of the use of amide salts in substitution reactions on chlorophosphazene precursors. The anilide anion was shown to be a powerful nucleophile in substitution reactions on various trimer derivatives, but investigations of such reactions with the high polymer have not been reported.22 Where strong nucleophiles (such as amide salts) with low steric requirements are employed, the usual pentacoordinate transition state (Scheme 1), may be a viable reaction intermediate which can undergo alternative modes of decomposition, perhaps involving chain cleavage and/or cross-linking. 

In contrast, C=0-containing carboxylic acid and carbonic acid derivatives react with nucleophiles in substitution reactions. The one group or one of the two groups bound through a heteroatom to the carboxyl carbon of these substrates is substituted so that compounds A or B, respectively, are obtained. 

A characteristic of organic sulfur compounds, especially volatile (low molecular mass) thiols, is their disagreeable odors. For example, 3-methyl-1-butanethiol and 2-butene-1-thiol are ingredients of a skunk s perfume, and methanethiol or ethanethiol is usually added, in small amounts, to natural gas, which is odorless by itself, so that leaks can be readily detected. The chemical properties of thiols and sulfides differ from those of alcohols and ethers in that thiols are somewhat stronger acids than alcohols and the sulfur atoms of these compounds are considerably more nucleophilic than the oxygen of their analogs. They are excellent nucleophiles in substitution reactions. 

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 ... 

RCO , an indifferent nucleophile in prohc solvents, enjoys a large rate enhancement, permitting rapid alkylation with haloalkanes in hexamethylphosphoric triamide [301, 302], When the Williamson ether synthesis is carried out in dimethyl sulfoxide [303], the yields are raised and the reaction time shortened. Displacements on unreactive haloarenes become possible [304] (conversion of bromobenzene to tert-butoxybenzene with tert-C UgO in dimethyl sulfoxide in 86% yield at room temperature). The fluoride ion, a notoriously poor nucleophile or base in protic solvents, reveals its hidden capabilities in dipolar non-HBD solvents and is a powerful nucleophile in substitution reactions on carbon [305],... 

The use of carbonylate anions as nucleophiles in substitution reactions at metals has been used for a long time to prepare other Re-M metal-bonded derivatives, for example, ReCo(CO)9 from [Re(CO)6]+ and [Co(CO)4] and (168) from [ReBr(CO)4]2 and [Fe(C0)4 C(0)R ][NMe4]. ... 

The most important reactions of tetrazolate anions are alkylations in which the anion is used as a nucleophile in substitution reactions mainly with alkyl halides and sulfates. Many such reactions have been reported and a variety of conditions and reagents have been employed. The products are mixtures of iV(l)- and iV(2)-alkyl isomers, the relative proportions of which depend upon the conditions of the alkylation and the influence of the 5-substituent. In general, electron-donating substituents at C-5 tend to favor slightly alkylation at the N(l)-site while electron withdrawing substituents favor 1V(2)-alkylation. The position of alkylation was also influenced by the steric requirements of the alkylating agent and was found to be insensitive to electronic effects of para-substituents on benzyl... 

The lone pairs may act as nucleophiles in substitution reactions of alkyl halides and sulfonates, in the solvolysis of epoxides, and in addition reactions to carbonyl groups. These reactions often proceed with acid or base catalysis. 

Cr, Br, and 1 are good nucleophiles in substitution reactions at sp hybridized carbons, but they are ineffective nucleophiles in addition. Addition of Cl" to a carbonyl group, for example, would cleave the C—O 7i bond, forming an alkoxide. Because Cl" is a much weaker base than the alkoxide formed, equilibrium favors the starting materials (the weaker base. Cl"), not the addition product. 

Hard and soft nucleophiles in substitution reactions are discussed in Chapter 17. 

Alkyl halides react with nucleophiles in substitution reactions and with bases in elimination reactions. 

In the reaction of the bromoacyl chloride with methanol, attack occurs at the carbonyl group with an alcohol because oxygen nucleophiles are hard nucleophiles (controlled by charge interactions). If we want to displace the a-bromo group we can use any soft (orbital-dominated) nucleophile. Triphenylphosphine (PhjP) is particularly important—the product is a phosphonium salt, employed in Wittig reactions and discussed in Chapters 11 and 27. Hard and soft nucleophiles in substitution reactions are discussed in Chapter 15. 

As we saw in Chapter 7, alkoxide ions can also be used as nucleophiles in substitution reactions. 

Many of the reagents commonly used as nucleophiles in substitution reactions are also bases, and they can thus promote elimination reactions. Since both elimination and substitution reactions commence from alkyl-LG species, it is not surprising that substitutions and eliminations are often competitive, and we gave some examples in Section 10.13.3. Now that we have considered both substitutions and eliminations, let s analyze the competition. 

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