Extranuclear Alkylation

Most alkoxy- or aryloxyquinoxalines have been made by primary synthesis (see Chapter 1), by alcoholysis or phenolysis of halogenoquinoxalines (see Sections 3.2.2 and 3.4.2), or by 0-alkylation of tautomeric quinoxalinones or extranuclear hydroxyquinoxalines (see Sections 4.1.2.2 and 4.3.2). The remaining preparative routes are illustrated by the following classified examples. 

Note The alkylation of nuclear or extranuclear aminoquinoxalines is an unattractive process, and examples are limited. Initial acylation of an aminoquinoxaline is sometimes used to assist subsequent alkylation, and the acyl group can be removed later with ease. 

Bromo-8-(p-hydroxyanilino)-1,5-naphthyridine underwent extranuclear Mannich alkylation to give 3-bromo-8-[4-hydroxy-3,5-bis(4-methylpiperazin-l-yl)ani-lino]- 1,5-naphthyridine (31) (substrate, CH20, 1-methylpiperazine, EtOH, reflux, 30 h 50%) analogs likewise.1379... 

Most such esters have been made by primary synthesis (see Chapter 22) and some by esterification of corresponding carboxylic acids (see Section 28.1.2) or from halogeno-1,8-naphthyridines (see Section 24.2). A few extranuclear esters have been prepared by passenger alkylations. For example, by S-ethoxycarbonyla-tion as in Chapter 26. 

The conversion of one (unsubstituted-alkyl) pyrazine into another such pyrazine by extranuclear alkylation has been covered in Section 3.2.1.4. The similar formation of (substituted-alkyl)pyrazines is illustrated here. 

Nuclear and extranuclear C-alkylation has been discussed in detail in Sections 2A(2) and 2A(3), respectively. 

A variety of 4-amino-5-alkoxy- and acyloxy-l,3-disubstituted-pyrazoles have been treated with alkylating agents such as alkyl halides to give 4-dialkylamino-3-pyrazolin-5-ones.525 There is a simultaneous alkylation of ring nitrogen and extranuclear nitrogen. 

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