Halogeno Substituents

The preparations of fluoro- and iodopyrazines, some of which involved the displacement of chloro substituents, have been discussed in Sections IH and 11. 

Tetrafluoropyrazine has been converted to 2,3,5-trifluoro-6-hydrazinopyrazine and thence to 2-chloro- and 2-bromo-3,5,6-trifluoropyTazine by reaction with ferric chloride in concentrated hydrochloric acid and cupric bromide in aqueous 

2-Dimethylamino-3,5,6-trifluoropyrazine with aluminum trichloride at lOO gave 2-chloro-6-dimethylamino-3,5-difluoropyrazine, 2-chloro-5-dimethylamino- 

6- difluoropyrazine similarly gave 2,6-dichloro-3-dimethylamino-5-fluoropyrazine, and 2-chloro-5,6-bis(dimethylamino)-3-fluoropyrazine gave 2,3-dichloro-5,6-bis(dimethylamino)pyrazine (888), 

Passage of hydrogen bromide into a refluxing solution of tetrachloropyrazine in acetic acid has been shown to give tetrabromopyrazine (889) and 2-bromo- 

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Transhalogenation, or the replacement of one halogeno substituent by another, is of little interest as a reaction but of great preparative importance. Accordingly, it is discussed in Section 2.13.3.3.9/. 

The independence of the composition of the reaction products from the nature and position of the halogeno substituent clearly demonstrates that the amination of the isomeric 3- (27, X = Cl, Br, I) and 4-halogenopyridines (32, X = Cl, Br, I) proceeds exclusively via 3,4-pyridine (31). It is surprising that the 4-halogenopyridines did not... 

This method is attractive, since polymers with good thermal stability are obtained, especially with aryl or halogeno substituents.165 174 Moreover, a number of substituted polyester LCPs exhibit solubility in common organic solvents, thus facilitating their structural characterization. However, the cost of starting monomers has hampered the commercial development of thermotropic polyesters based on substituted monomers. 

The conversion of a primary amino substituent into a halogeno substituent is usually done by diazotization in the presence of an excess of the appropriate halogenide ion, by treatment in a nonaqueous solvent with alkyl nitrite and copper (II) halogenide, or by treatment with a freshly made solution of bromopyridinium perbromide [(CH)5N+ Br. Br2 ] or the like. These routes are illustrated in the following examples. 

The replacement of one halogeno substituent by another at the 2- or 3-position may be done directly by several methods similar transformations at the 5- to 8-positions normally require an indirect route. The following examples illustrate typical procedures. 

Note Even when two halogeno substituents occupy the activated 2- and 3-positions, it is usually possible to achieve monoaminolysis under gentle conditions after replacing one such halogeno substituent, the other is substantially deactivated by the adjacent amino group and hence requires more severe conditions to bring about diaminolysis. 

Note Even from the limited number of recent preparative results that follow, it is evident that the interannular activating effect of a 6/7-nitro group on a 2/3-halogeno substituent is appreciable and that the effect of an adjacent nitro group on a normally unreactive 5-, 6-, 7-, or 8-halogeno substituent is so substantial that aminolysis becomes a practical procedure. 

Note From available recent examples, it is not clear whether the A -oxidation of a halogenoquinoxaline has much activating effect on the halogeno substituent. 

Provided they occupy the 2- or 3-position in regular quinoxalines or the 2-, 3-, 6-, or 7-position in 5,8-quinoxalinequinones, halogeno substituents are easily... 

Whether activated or not, halogeno substituents may be removed in favor of hydrogen by chemical reduction or by catalytic hydrogenation (usually in the presence of a base and often accompanied by nuclear reduction). Such dechlorination may also be achieved by loss of hydrogen halide from a nucleus-reduced quinoxaline. The following examples illustrate these procedures. 

Intermolecular Cyclizations Involving Two Adjacent Halogeno Substituents... 

Note The introduction of extranuclear halogeno substituents into quinoxalines by halogenoalkylation, halogenoacylation, halogenoarylaminolysis, and the like is well illustrated in appropriate chapters of this book. A single atypical example is given here. 

The main preparative routes to quinoxaline ketones have been discussed earlier by primary synthesis (Chapter 1), by extranuclear acylation of alkylquinoxalines (Section 2.2.4), by oxidation of appropriate alkylquinoxalines (also Section 2.2.4), by displacement of a halogeno substituent (Section 3.2.7), by oxidation of... 

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