2-Methylquinoxaline, reaction with

Quinoxalines substituted in the 5- or 6-position generally follow the pattern of reactions expected for substituted benzene derivatives, although recently there have been reports of interesting and unexpected reactions with nucleophiles (see Section III, A,2 and references 85-90). 6-Methylquinoxaline is brominated in the side chain when treated with N-bromosuccinimide in carbon tetrachloride in the presence of azobisiso-butyronitrile, to form 6-bromomethylquinoxaline.182... 

Methylquinoxaline also undergoes a novel cycloaddition reaction with two equivalents of tetrachloro-l,2-benzoquinone129 (see Section III,A) with formation of a quinoxaline-orange type product. The reaction probably proceeds by initial formation of the quaternary salt 231 which by elimination of HC1, followed by protonation and dehydration, leads to the cyclized product 232. This on reaction with a further equivalent of tetrachloro-l,2-benzoquinone at the C=N function gives the final yellow compound 117. 

Chloro-3-methylquinoxaline (7) undergoes reaction with a / ,7-unsaturated Grignard reagent to give the 2-allylquinoxaline derivative 8, which is obtained as an oil. 

Methylquinoxalin-2(l//)-one undergoes reaction with tris(dimethylamino)methane to yield 3-[( )-jS-dimethylaminovinyl]quinoxalin-2(l//)-one... 

Quinoxalin-2-ylmethyllithium (8), prepared by lithiation of 2-methylquinoxaline with lithium diisopropylamide, undergoes an alkylation reaction with bis(trimcthylsilyl)peroxide to yield 2-ethylquinoxaline (9) as an oil. ... 

Methylquinoxaline undergoes reaction with Grignard reagents, e.g. ethylmagnesium bromide, phenylmagnesium bromide, to yield 2-alkyl- or 2-aryl-3-methylquinoxaline and 2-alkyl- or 2-aryl-3-methyl-l,2-dihydroquinoxaline. In case of ethylmagnesium bromide, some dimerization product is also formed. ... 

The H-D exchange rates of a series of a-methylazines, including 2-methylquinoxaline, have been determined. " The anion of 2-methylquinoxaline generated in liquid ammonia with potassamide reacts with n-propyl nitrate to give 2-nitromethylquinoxaline (50) in 58% yield." " 2-Dichloronitromethylquinoxaline (51) is formed when 2-nitromethylquinoxaline is treated with sodium hypochlorite." Treatment of 2,3-dimethylquinoxaline with sodamide in hexamethylphosphoramide (HMPT) similarly gives a dianion which on reaction with methyl iodide is converted into 2,3-diethylquinoxaline in 75% yield." ... 

Alkyl and arylmagnesium halides react with 2-methylquinoxaline by addition of one mole of reactant to the 3,4-bond. After hydrolysis the 2-alkyl- or 2-aryl-l,2-dihydro-3-methylquinoxalines (52) are obtained. When ethylmagnesium bromide is used a dimeric by-product (53) is also isolatedReaction of 2,3-dimethylquinoxaline with benzonitrile and lithium amide gives l-amino-l-phenyl-2-(3-methyl-2-quinoxalinyl)-ethylene (54). The mono- and dilithium salts of 2,3-dimethylquinoxaline have been generated from the quinoxaline by reaction with one or two equivalents of lithium diisopropylamide (LiNPr, respectively. These salts have been reacted with a variety of electrophilic reagents such as alkyl halides, aryl ketones, esters, and nitriles. " ... 

Methyl- and 2,3-dimethylquinoxaline also undergo interesting addition reactions with dimethyl acetylenedicarboxylate. Addition of 2-methylquinoxaline to two molecules of the ester results in the formation of the isomeric azepino[l,2-a]quinoxalines 61 and 62. Addition is accom-... 

Quinoxaline and 2-methylquinoxaline react with diphenylcyclo-propenone (75) to give the products 76, analogous to that obtained from the reaction of 75 with pyrazine (see Chapter XIX). The formulation of the products as 1-hydroxy rather than 1,5-dihydro-1-oj o compounds is discussed in Section II. The thioxo analogue of 75 give the 1-mercapto derivative 77 on reaction with quinoxaline. No spectral details are given to permit discussion of possible tautomerism of this compound to the 1,5-dihydro-1-thioxo derivative. 

Benzofuroxan (150) on reaction with ethyl acetoacetate provides the methylquinoxaline 151, which on bromination gives the bromomethyl derivative 152. Treatment of this compound with amines gives the monooxopyrrolo compound 154. The 2-methyl derivative 154 (R = Me) was also prepared directly from benzofuroxan by reaction with the JV-methylpyrrolinone 153. The products 154 are claimed to be antibacterials and animal growth promotants. ... 

An interesting special case is the reaction of 2-methylquinoxaline (212) with tetrachloro-o-benzoquinone (Scheme 49), which gives the hexacyclic product (214), presumably via the intermediate salt (213) (70CJC327). 

Reaction of nitromalon-bis-A -methylanilide (105) with sulfuric acid gives A -methylisatin- -oxime (107) and not 4-methylquinoxalin-3-one 1-oxide (108) as originally suggested. This transformation may involve a Beckmann-type rearrangement of the protonated aci-nitro compound (106) prior to dehydrative ring closure. ... 

Reaction of 1,2-diaminobenzene with l,l,l-trifluoro-2,3-alkanediones gives trifluoromethylquinoxalines in high yields <2001JHC773>, and that with perfluoro-2,3-butanedione mono(dimethylhydrazone) gives 2,3-trifluoro-methylquinoxaline <2000TL9267>. 

Quinoxaline has been prepared by the reaction of glyoxal with o-phenylenediamine, and 2-methylquinoxaline by the reaction of pyruvic aldehyde or isonitrosoacetone with < -phenylenedi-amine. 2,3-Pyrazinedicarboxylic acid has been prepared only by the permanganate oxidation of quinoxaline. 2-Methyl-5,6-pyrazinedicarboxylic acid has been prepared from 2-methyl-quinoxaline in the same way. - ... 

Quinoxaline and 2-methylquinoxaline form 1 1 adducts (111) with diphenylcyclopropenone,122 and an analogous pyrrolo[l,2-a]quin-oxaline has been isolated from the reaction of quinoxaline with di-phenylcyclopropenethione.123... 

Elina and co-workers have extensively investigated the reactions of 2-methylquinoxaline 1,4-dioxide and 2,3-dimethylquinoxaline 1,4-dioxide with aldehydes.206 Under alkaline conditions formalin gives hydroxy-ethyl derivatives, and aryl aldehydes form styrylquinoxalines. As expected, 2,3-dimethylquinoxaline 1-oxide yields 3-methyl-2-styrylquin-oxaline 1-oxide.207... 

Quinomethionate (91) (60AG973) is made by reaction of 6-methylquinoxaline-2,3-dithiol with carbonyl chloride. It is used to control spider mites, and also has fungicidal properties. An experimental acaricide containing the unusual trifluoromethylimino group is the thiazolidine (92) (72GEP2062348). It is made by reaction of Af.fV -diphenylthiourea with the highly fluorinated intermediate (93). 

Double hydrogenation of 2-methylquinoxaline using (R)-4 with an S/C of 100 under 5 atm of H2 afforded (S)-2-methyl-l,2>3,4-tetrahydroquinoxaline in 90% ee and in a 53.7% yield (Scheme 11) [24]. When the reaction proceeded under lower H2 pressure, a higher optical yield was obtained. The two C=N bonds were hydrogenated at comparable rates. 

Treatment of isonitrosoacetone with 5-fold excess sodium hydrogen sulfite in water followed by the addition of an equimolar amount of benzene-1,2-diamine gives 3-methylquinoxalin-2-amine (mp 163-164°C) in 70% yield. The reaction proceeds through a bis-adduct with the sulfite.In the absence of sodium hydrogen sulfite the yield is only 42%. ... 

Methylquinoxaline and some of its 6,7-substituted derivatives give 4-methylquinoxalin-ium methosulfates and perchlorates. The reactions must be carried out under an inert atmosphere to avoid oxidative dimerization. 2,3-Dimethylquinoxaline is quatcrnizcd with dimethyl sulfate to give 1,2,3-trimethyl quinoxalinium methosulfate. ... 

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