Quinoxaline chloro-, preparation

Kinetic studies have been carried out on the displacement reactions of various chloroazanaphthalenes with ethoxide ions and piperi-dine. - 2-Chloroquinoxaline is even more reactive than 2-chloro-quinazoline, thus demonstrating the powerfully electrophilic nature of the -carbon atoms in the quinoxaline nucleus. The ease of displacement of a-chlorine in the quinoxaline series is of preparative value thus, 2-alkoxy-, 2-amino-, - 2-raethylamino-, 2-dimethyl-amino-,2-benzylamino-, 2-mercapto-quinoxalines are all readily prepared from 2-chloroquinoxaline. The anions derived from substituted acetonitriles have also been used to displace chloride ion from 2-chloroquinoxaline, ... 

Aryl-5-oxo-1,2,3,5-tetrahydropyrido[ 1,2,3-i/e]quinoxaline-6-carboxy-mides were prepared from 7-chloro derivatives and arylboronic acids in the presence of Na2C03, diphenylphosphinated divinylbenzene-crosslinked polystyrene and Pd(PPh3)4 catalyst. 7-Chloro derivatives were obtained from 7-hydroxy derivatives by heating in POCI3 at 50°C for 3 h (01MIP12). 

Brightener structures of only moderate molecular size are of interest for white grounds in the transfer printing of polyester fabrics. Derivatives of 6-acetamidoquinoxaline with an electron-donating substituent (X) in the 2-position (11.48) were prepared by converting quinoxalin-2-one to 2-chloro-6-nitroquinoxaline and condensation with amines (X = RNH), alcohols (X = RO) or phenols (X = PhO), followed by reduction and acetylation (Scheme 11.19). The nitro intermediates (11.49) are also of interest as low-energy disperse dyes for polyester [61]. 

Condensed quinoxalines have been synthesized using 2-chloro-3-alkynylquinoxalines as common intermediates. 2-Chloro-3-phenylethynylquinoxaline 98 was prepared from 2,3-dichloroquinoxaline (97). Action of methylamine on 98 gave 1,2-disubstituted pyrrolo[2,3-fcjquinoxaline 99. Similarly, 2-phenylthieno[2,3-fc]quinoxaline 100 was synthesized by treating 98 with ethanolic sodium sulfide. 

The most convenient synthesis of halogenopyrazines and -quinoxalines is by halogenation of pyrazinones and quinoxalinones with phosphoryl or other acid halides for example, 5-hydroxy-2-pyrazinecarboxylic acid, rather than 5(477)-pyrazinone-2-carboxylic acid, is chlorinated with phosphorus pentachloride/phosphoryl chloride to afford a 63% yield of 5-chloro-2-pyrazinecarbonyl chloride <1994SL814>. Sato and Narita provided an improved synthesis of various halogenopyrazines in which 2(l//)-pyrazinones were activated with chlorotrimethylsilane to give silyl ethers (Section 8.03.7.3). This procedure is most effective for synthesis of bromopyrazines whose overall yields are 62-81% <1999JHC783>. Bromopyrazine is directly prepared by treatment of 2-(l//)-pyrazinone with phosphoryl... 

Some very clever syntheses of pyrazines were reported. Tandem Mn02-mediated oxidation followed by in situ trapping with aromatic or aliphatic 1,2-diamines was shown to give rise to quinoxalines, dihydropyrazines, pyrazines, and piperazines without the need to isolate highly reactive 1,2-dicarbonyl intermediates <03CC2286>. A new intramolecular cyclization route to highly substituted chiral 6,7-dihydro-5//-imidazo[l,5-a]pyrazin-8-ones like 157 from Meldrum s acid was developed <030L3907>, and 5-chloropyrido[3,4-6]pyrazines were prepared from 1,2-dicarbonyl compounds and 2-chloro-3,4-diaminopyridine <03H(60)925>. A synthesis of... 

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... 

The chemistry of 2-chloro- and 2,3-dichloroquinoxalines has been previously reviewed in Simpson s monograph/ The present review further demonstrates the extensive use which these derivatives have found in the preparation of other quinoxalines. This is a result of the ease with which nucleophilic displacement of halogen from the 2- and 3-positions can be carried out. 

Chloroquinoxalines have also been prepared from quinoxaline mono-N-oxides. For example, treatment of 5-methylquinoxaline 1-oxide with phosphoryl chloride gives 2-chloro-5-methylquinoxaline, and reaction of... 

Many 2-chloro-3-substituted quinoxalines have been prepared from... 

Alkylquinoxalines have also been prepared by various transformations of preformed quinoxalines. Thus 2-carboxy groups are usually readily decarboxylated and 2-chloro groups removed by catalytic hydrogenation. Illustrative of this approach is the reduction of 2-chloro-3-methylquinoxaline to 2-methylquinoxaline. " ... 

Reaction of 2-chloro 3-substituted quinoxalines 22 with hydrazines provides another simple preparation of pyrazolo[3,4-h]quinoxalines. The parent heterocycle 23 has been obtained by treating the aldehyde 22 (R = CHO) or the dibromomethyl derivative 22 (R = CHBr2) with hydrazine. Similarly the nitrile 22 (R = CN) has given the 3-amino compound 24 in 72% yield, and methylhydrazine with the ester 22 (R = COjEt) gave the 3-hydroxy derivative 25. In spite of the ready cyclization of the aldehyde 22 (R = CHO) with hydrazine, the corresponding... 

Oxidation of the parent base with hydrogen peroxide in formic acid gives a high yield of mono-N-oxide and a little di-N-oxide N-Oxidation is assumed to proceed preferentially at the less hindered 4-nitrogen. A number of substituted benzo[/]quinoxaline 4-oxides have been prepared, the majority by oxidation of the appropriate benzo[/]quinoxaline with peracids. " Treatment of benzo[/]quinoxaline 4-oxide with phosphoryl chloride gives mainly 3-chlorobenzo[/]quinoxaline. An isomeric mono-chloride, m.p. 104-104.5°, is also isolated from this reaction which is shown by independent synthesis not to be the 2-chloro derivative. A dichloro derivative, m.p. 187-188°, of unknown structure is obtained by treatment of the parent base with chlorine in glacial acetic acid. A disubstitution product of unknown orientation and m.p. 288° is obtained by nitration of... 

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