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1、302 CHAPTER 8 NUCLEOPHILIC SUBSTITUTION W hen we discussed elimination reactions in Chapter 5, we learned that a Lewis base can react with an alkyl halide to form an alkene. In the present chapter, you will fi nd that the same kinds of reactants can also undergo a different reaction, one in which th
2、e Lewis base acts as a nucleophile to substitute for the halide substituent on carbon. We fi rst encountered nucleophilic substitution in Chapter 4, in the reaction of alcohols with hydrogen halides to form alkyl halides. Now well see how alkyl halides can them- selves be converted to other classes
3、of organic compounds by nucleophilic substitution. This chapter has a mechanistic emphasis designed to achieve a practical result. By understanding the mechanisms by which alkyl halides undergo nucleophilic substitution, we can choose experimental conditions best suited to carrying out a particular
4、functional group transformation. The difference between a successful reaction that leads cleanly to a desired product and one that fails is often a subtle one. Mechanistic analysis helps us to appreciate these subtleties and use them to our advantage. 8.1FUNCTIONAL GROUP TRANSFORMATION BY NUCLEOPHIL
5、IC SUBSTITUTION Nucleophilic substitution reactions of alkyl halides are related to elimination reactions in that the halogen acts as a leaving group on carbon and is lost as an anion. The car- bonhalogen bond of the alkyl halide is broken heterolytically: the pair of electrons in that bond are lost
6、 with the leaving group. ? Alkyl halide RX Lewis base Y ? Product of nucleophilic substitution RY? Halide anion X ? BackForwardMain MenuTOCStudy Guide TOCStudent OLCMHHE Website 8.1Functional Group Transformation by Nucleophilic Substitution303 The most frequently encountered nucleophiles in functio
7、nal group transformations are anions, which are used as their lithium, sodium, or potassium salts. If we use M to represent lithium, sodium, or potassium, some representative nucleophilic reagents are Table 8.1 illustrates an application of each of these to a functional group transfor- mation. The a
8、nionic portion of the salt substitutes for the halogen of an alkyl halide. The metal cation portion becomes a lithium, sodium, or potassium halide. Notice that all the examples in Table 8.1 involve alkyl halides, that is, compounds in which the halogen is attached to an sp3-hybridized carbon. Alkeny
9、l halides and aryl halides, compounds in which the halogen is attached to sp2-hybridized carbons, are essentially unreactive under these conditions, and the principles to be developed in this chapter do not apply to them. To ensure that reaction occurs in homogeneous solution, solvents are chosen th
10、at dis- solve both the alkyl halide and the ionic salt. The alkyl halide substrates are soluble in organic solvents, but the salts often are not. Inorganic salts are soluble in water, but alkyl halides are not. Mixed solvents such as ethanolwater mixtures that can dissolve enough of both the substra
11、te and the nucleophile to give fairly concentrated solutions are fre- quently used. Many salts, as well as most alkyl halides, possess signifi cant solubility in dimethyl sulfoxide (DMSO), which makes this a good medium for carrying out nucle- ophilic substitution reactions. sp2 -hybridized carbonsp
12、3 -hybridized carbon Alkyl halide C X Alkenyl halide X CC Aryl halide X Nucleophilic reagent M? ?Y?RX Alkyl halide RY Product of nucleophilic substitution ?X ? M? Metal halide MOR MOCR O X MSH MCN MN3 (a metal alkoxide, a source of the nucleophilic anion)RO ? (a metal hydrogen sulfide, a source of t
13、he nucleophilic anion)HS ? (a metal cyanide, a source of the nucleophilic anion)CPN ? (a metal azide, a source of the nucleophilic anion NNN ? ) (a metal carboxylate, a source of the nucleophilic anion RCO O X ) ? ?Y RXRY ? X ? RXX ? I, Br, Cl, F ? The carbonhalogen bond in an alkyl halide is polar
14、and is cleaved on attack by a nucleophile so that the two electrons in the bond are retained by the halogen Alkenyl halides are also re- ferred to as vinylic halides. The use of DMSO as a sol- vent in dehydrohalogenation reactions was mentioned earlier, in Section 5.14. BackForwardMain MenuTOCStudy
15、Guide TOCStudent OLCMHHE Website 304CHAPTER EIGHTNucleophilic Substitution TABLE 8.1 Representative Functional Group Transformations by Nucleophilic Substitution Reactions of Alkyl Halides Nucleophile and comments Cyanide ion (:C ? PN :) The negatively charged carbon atom of cyanide ion is usually t
16、he site of its nucleophilic character. Use of cyanide ion as a nucleophile permits the extension of a carbon chain by carboncarbon bond formation. The product is an alkyl cyanide, or nitrile. (Continued) Alkoxide ion (RO:?) The oxygen atom of a metal alkoxide acts as a nucleophile to replace the halogen of an alkyl halide. The product is an ether. : Hydrogen sulfide ion (HS:?) Use of hydrogen sulfide as a nucleophile permits the conversion of alkyl hal- ides to compounds of the type RSH.
