Quinoxaline-2-thiones

Pyrimidine-2-thiones (e.g., 206) have been shown to exist as such by comparison of their ultraviolet spectra with those of both alkylated forms.The ultraviolet spectra of pyrimidine-4-thiones are different from those of 4-alkylthiopyrimidines, therefore the former compounds exist as 207 and/or 208, the predominant form not having been determined. Infrared spectral evidence suggests that quinazoline-4-thione exists as 209 and/or 210 and has been used recently to demonstrate the thione formulation for pyrimidine-2- and -4-thione, pyrazine-2-thione, and quinoxaline-2-thione. In view of this work, the report that X-ray crystallographic evidence supports the mer-... 

Pyrazine-2-thione (213) and quinoxaline-2-thione (214) probably exist in the thione form since their ultraviolet spectra are different from those of the 2-methylthio analogs. The basicity of quinoxaline-2-thione is 1.4 pK units less than that of 2-methylthio-quinoxaline, and the ultraviolet spectra of the cations are dissimilar. Presumably quinoxaline-2-thione and its 2-methylthio derivative do not form similar cations (215, P = alkyl, H), and it would appear that either the thione gives the cation 216 or the 2-thioether gives the cation 217. Similar considerations apply to pyrazine-2-thione. 

G. Reactions and Tautomerism of Quinoxaline-2-thione and Quinoxaline-2,3-dithione (2-Meecapto- and 2,3-Dimercapto-quinoxaline)... 

Treatment of quinoxaline-2-thione (85) with methyl iodide and alkali gives 2-methylthioquinoxaline (86) and apparently no 1-methyl-quinoxaline-2-thione (87). The latter compound is prepared conven-... 

The acidic strength of various quinoxaline derivatives is also listed in Table II. -Methyl groups have an acid-weakening effect and quinoxalin-2-one (2-hydroxyquinoxaline) is, as expected, a weaker acid than quinoxaline-2-thione (2-mercaptoquinoxaline), The marked enhancement of the acidic strength of 5-hydroxyquinoxaline 1-methiodide compared to 5-hydroxyquinoxaline itself, is due to the electron-attracting property of the positively charged nitrogen, ... 

It is interesting to note that, due to the reversible character of the cycloaddition, isomerization favoring the product which is thermodynamically more stable may occur and an appropriate side-chain substituent may participate. For example, the thiazolo [4,5-b] quinoxalines 55, formed in the reaction of quinoxalinium salts with thioamides under kinetically controlled conditions, are able to undergo two different isomerizations (Scheme 45). When compound 55 contains an aryl group at C-2 (R2 = aryl) and this compound is heated in an ethanolic solution, the thiazoloquinoxaline 57 is formed. In the case of R2 = CH3, the methyl group participates in the isomerization process, yielding pyrrolo [2,3-b]quinoxalin-2-thione 58 (Scheme 45) (85KGS396). 

Fig. 3. Neutral molecules of quinoxaline-2-thione (--------), l-methylquinoxaline-2-thione (-------), and 2-methylmercapto-... 

Thioquinox (33), l,3-dithiolo[4,S-b]quinoxaline-2-thione, is primarily an acar-icide with mainly ovicidal properties. The compound is practically insoluble in water and is stable to the action of light and heat. It is also resistant to hydrolysis, and although sulfur is oxidised in the molecule, the biological action is not reduced. 

Hydroxy- and 2-mercaptoquinoxalines exist in the quinoxalin-2-one (Chapter V) and quinoxaline-2-thione forms (Chapter VI), whereas 2-aminoquinoxaline exists as such rather than as an imine (Chapter XI) (Scheme 4). 

Quinoxaline-2-thione (2) is prepared from 2-chloroquinoxaline by treatment with thiourea in methanol, followed by hydrolysis of the resulting isothiouronium salt (1) with 2.5 M sodium hydroxide. A number of other quinoxaline-2-thiones have been prepared by this method, in most cases without the isolation of the intermediate isothiouronium salt. 3-Hydrazinoquinoxaline-2-thiones are obtained from the corresponding 2-chloro-3-hydrazinoquinoxalines by treatment with an aqueous solution of alkali sulfide or alkali hydrogen sulphide.3-Amino-quinoxaline-2-thione has been prepared similarly by treating 2-amino-3-chloroquinoxaline with methanolic potassium hydrogen sulfide in an... 

Various 3-substituted aminoquinoxaline-2-thiones have been prepared from quinoxaline-2,3-dithione. For example, treatment of the dithione with methylamine yields 3-methylaminoquinoxaline-2-thione, and the corresponding reaction with hydrazine hydrate yields 3-hydrazino-quinoxaline-2-thione. The latter compound is also obtained by treatment of 2,3-dichloroquinoxaline with thiourea and then with hydrazine hydrate. When 2-chloroquinoxaline 1-oxide is heated with thiourea in methanol at room temperature, an unidentified solid m.p. 184-185° is obtained alkaline hydrolysis of methanol-soluble products gives quinoxaline-2-thione in 41% yield. A method of some general applicability is illustrated by the preparation of the thioxo compound 4 from o-anilinoaniline (3). °... 

Quinoxaline-2-thione is a very weak base of pK -1.24 and has an acidic pKa of 7.16. Comparison of its ionization and ultraviolet absorption properties with those of 2-methylthioquinoxaline (pK 0.26) and 1,2-dihydro-l-methyl-2-thioxoquinoxaline (pXa-1.01) shows that quinox-aline-2-thione exists in solution in the thioamide form (2a) rather than as the thiol (2b). 

Quinoxaline-2-thione is readily converted into 2-hydrazinoqmnoxaline on treatment with hydrazine hydrate, and 3-hydrazinoquinoxaline-2-thione is readily hydrolyzed (2.5 M HCl at 70°) to quinoxaline-2,3-dione. The sodium salt of quinoxaline-2-thione has been S-alkylated with a wide range of alkyl halides to give 2-quinoxalinyl sulfides,but attempts to carry out a parallel reaction with p-nitrochlorobenzene failed. p-Nitrophenyl-2-quinoxalinyl sulfide (5) can however be prepared by reaction of 2-chloroquinoxaline with the sodium salt of p-nitro-benzenethiol. ... 

A number of 3-chloro-, 3-methoxy-, and 3-methylthioquinoxaline-2-thiones have been reacted with acylating agents such as alkyl chlorofor-mates, alkyl chlorothioformates, and thiophosgene in the search for compounds for use as pesticides. For example, treatment of 3-chloro-quinoxaline-2-thione with ethyl chloroformate gives the ester 9. 

As already indicated, many acylated quinoxalinethiones have been synthesized as potential pesticides/ Quinoxaline-2-thiones have been tested for antitubercular activity and 3-hydrazinoquinoxaline-2-thione has been incorporated into an antileprosy ointment/ Hydrazones of 3-hydrazinoquinoxaline-2-thione have antibacterial activity/... 

Hydrazinoquinoxalines have also been prepared by the action of hydrazine hydrate on quinoxalin-2-ones and quinoxaline-2-thiones. ... 

---