Reactions of Substituents Attached to Ring Carbon Atoms

7 Reactions of Substituents Attached to Ring Carbon Atoms 

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No information is available regarding the reactions of substituents attached to ring carbon atoms. 

Conversion of the nitro to cyano group in compound 110 involved a number of reactions of substituents attached to ring carbon atoms (Scheme 2) <1999H(51)1661>. Diozatization under typical conditions followed by reaction with Na3[Cu(CN)4] at pH 1 afforded the cyano derivative 111. 

REACTIONS OF SUBSTITUENTS ATTACHED TO RING CARBON ATOMS... 

There have been numerous reports of reactions of substituents attached to ring carbon atoms and it is not possible to list them all here. Instead, the major types of reaction are shown in Table 3 together with representative examples. As will be obvious from this table, the vast majority of reactions of this type have been reported for the imidazo[2,l-6]thiazole ring system (15). 

The final stages of the synthesis of (—)-A-58365B, a Streptomyces metabolite that inhibits the angiotensin-converting enzyme, involve several reactions at substituents attached to ring carbon atoms of a quinolizidine system. Thus, ozonolysis of the exocyclic methylene side chain of compound 107, followed by base-induced elimination and carboxyl deprotection, gave 108 (Scheme 12) <1999JOC1447>. 

Reactivity of Substituents Attached to Ring Carbon Atoms 5.01.7.1 Reactions of the Benzenoid Ring of Benzotriazole... 

A wide variety of standard reactions for the transformation of substituents attached to ring carbon atoms have been reported in the literature. A selection of routine functional group transformations is summarized in Table 1 and in the few lines that follow. The selected examples can be classified according to the nature of the transformation, the reagents implicated, and the type of ring system E-M whose susbtituents underwent the modification. 

Since the publication of CHEC-II(1996), there have been very few examples related to the reactivity of substituents attached to ring carbon atoms. One case involves the reaction of 3-benzylidene-2,3-dihydro-2-methyl-l,2-benzothiazin-4-one 1,1-dioxide 163 with the alkylidenephosphorane derived from salt 164 forming the tricyclic-fused ring compound 165 (Scheme 20) <1996J(P1)2541>. This material 165 was oxidized with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) affording the biphenyl 166. Ring-opened product 167 was produced from 165 upon exposure to />-toluene-sulfonic acid and heat. 

Only a few reactions of the substituents attached to ring carbon atoms of bicyclic systems 1-34 have been reported. Methylation of compound 100 occurs at sulfur to give 101 (Equation 6) <2005BMC1847>. Horner-Emmons reaction of phosphonate 102 with benzaldehyde leads to triazole 103 as a single /. -stereoisomer (Equation 7) <2004TL1877>. 

A brief selection of reactions in which substituents attached to ring carbon atoms are involved in transformations is discussed. A large number of such reactions have been covered already in the different sections of this chapter. The transformations involving the formyl group at C-4 of the azetidin-2-ones have been reviewed recently <2004CME1921>. 

Reactivity of Substituents Attached to Ring Nitrogen Atoms 9.01.8.1 Reactions of Carbon Substituents... 

Reactions of substituents attached to the ring carbon atoms have only been reported sparingly. The results are shown in Scheme 7. 

As mentioned earlier, nucleophilic attack at ring carbon atoms a and y to a heteroatom is a reaction characteristic of the ir-deficient six-membered heterocycles. Within this context we do not regard hydrogen atoms attached to ring carbon atoms as substituent groups, and hence proton removal to generate a carbanionic centre is classified as a reaction at a ring carbon atom. There are thus six major reaction types, summarized in equations (21)—(26) in terms of the initial mechanistic steps. 

Very few reactions of substituents attached to bicyclic systems (l)-(26) have been reported. The only examples of reactions of a substituent attached to a ring carbon atom appear to be the methylation of (63), which occurs on sulfur yielding (64) (Equation (1)) <84JHC889>, and simple functionalizations of hydroxymethyl groups attached to the pyrrolo[l,2-c][l,2,3]triazole ring system <90SI56>. 

Table 3 Reactions of substituents attached to carbon atoms in ring systems (l)-(33).

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