Substitution reactions functional group transformation

Representative Functional Group Transformations by Nucleophilic Substitution Reactions of Alkyl Halides... 

Section 8 1 Nucleophilic substitution is an important reaction type m synthetic organic chemistry because it is one of the mam methods for functional group transformations Examples of synthetically useful nucleophilic sub stitutions were given m Table 8 1 It is a good idea to return to that table and review its entries now that the details of nucleophilic substitution have been covered... 

Chapter 11 focuses on aromatic substitution, including electrophilic aromatic substitution, reactions of diazonium ions, and palladium-catalyzed nucleophilic aromatic substitution. Chapter 12 discusses oxidation reactions and is organized on the basis of functional group transformations. Oxidants are subdivided as transition metals, oxygen and peroxides, and other oxidants. 

Organic halides play a fundamental role in organic chemistry. These compounds are important precursors for carbocations, carbanions, radicals, and carbenes and thus serve as an important platform for organic functional group transformations. Many classical reactions involve the reactions of organic halides. Examples of these reactions include the nucleophilic substitution reactions, elimination reactions, Grignard-type reactions, various transition-metal catalyzed coupling reactions, carbene-related cyclopropanations reactions, and radical cyclization reactions. All these reactions can be carried out in aqueous media. 

A new benzannulation methodology was developed in order to overcome the limitations of electrocyclic ring closure of divinylindoles. The cyclization is achieved via an allene-mediated electrocyclic reaction of 2,3-difunctionalized indoles. This method is more efficient for the synthesis of highly substituted 2-methyl carbazole alkaloids (559). The 3-alkenyl-2-propargylindole 557, a precursor for the allene intermediate, was prepared from 2-formylindole over several steps using simple functional group transformations (536,537) (Scheme 5.20). 

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 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. 

The rate at which reactions occur can be important in the laboratory, and understanding how solvents affect rate is of practical value. As we proceed through the text, however, and see how nucleophilic substitution is applied to a variety of functional group transformations, be aware that it is the nature of the substrate and the nucleophile that, more than anything else, determines what product is formed. 

Functional group transformations that rely on substitution by the SN1 mechanism are not as generally applicable as those of the SN2 type. Hindered substrates are prone to elimination, and rearrangement is possible when carbocation intermediates are involved. Only in cases in which elimination is impossible are SN1 reactions used for functional group transformations. 

These heterocyclization reactions provide initial products with a functionality (3 to the heteroatom, except for cases where a proton is the electrophile. Synthetic applications often depend upon further transformation of this functionality. Useful transformations include replacement by hydrogen, elimination to form a ir-bond, nucleophilic substitution, and substitution via radical intermediates. These reactions will be discussed only when understanding the cyclization step requires inclusion of the functional group transformation. 

The previous version of this section in CHEC-II(1996) summarized specific examples of the reactions of hydroxymethyl-substituted dioxetanes and also the deprotection of iV-acylamino-substitutcd dioxetanes <1996CHEC-II( 1B) 1041 >. As there have been no new examples over the last decade, the reader is directed to consult the previous chapter for details. It would also be worthwhile to consult reference <1991MI(12)567>, which summarizes basic functional group transformations that can be achieved while leaving the dioxetane moiety intact. 

The hydrolysis of a carboxylic acid derivative is but one example of a nucleophilic acyl substitution. Nucleophilic acyl substitutions connect the various classes of carboxylic acid derivatives, with a reaction of one class often serving as preparation of another. These reactions provide the basis for a large number of functional group transformations both in synthetic organic chemistry and in biological chemistry. 

In the previous section one of the two major aspects of silicon syntheses was described. A major problem for the organosilicon chemist is producing a silicon-carbon bond. A second synthetic area involves functional-group transformations. Most useful reactions at silicon centers are substitution processes. This is an important difference between the chemistry of silicon compounds and that of carbon compounds. The synthetic or reaction processes in organic compounds are increased enormously by the availability of double bonds present in olefins and carbonyl derivatives. In fact, substitution at sp3-carbon centers may represent the least interesting of organic reactions. 

Only a very few reactions, detailing straightforward functional group transformations, such as etherification and nitrile hydrolysis, have been reported for derivatives of the completely unsaturated pyrrolo[I,2-o]-pyrimidine nucleus (Scheme 3). In addition, hydrolysis of a substituted 8-cyanopyrrolo[ l,2-a]pyrimidine (25) to 4-aryl-2-aroyl-8-carboxamido-6,7-dimethylpyrrolo[1.2-a]pyrimidine (85) has been reported.10... 

Incorporation of halogen into a molecule is important because halides are often precursors for substitution or elimination reactions. The ability to convert alcohols to halides is therefore an important functional group transformation. The transform is... 

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