2- Methylquinoxaline alkylation

Alkyl side chains in both pyrazines and quinoxalines are susceptible to halogenation by elemental halogens (28JCS1960, 68TL5931) and under radical conditions with NBS (72JOC511). Thus, bromination of 2-methylquinoxaline with bromine in the presence of sodium acetate... 

Treatment of an alkaline solution of quinoxalin-2-one or quinoxa-line-2,3-dione with an alkyl iodide or sulfate results in A-methylation. Thus methylation of 3-aminoquinoxalin-2-one (74) with methyl sulfate and alkali gives 3-amino-l-methylquinoxalin-2-one (75) and not as previously reported the isomeric 0-methyl derivative. ... 

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. ... 

N-oxides of this type are accessible from o-nitroaniline-based syntheses (see earlier section). l,2-Dihydro-2-oxoquinoxaline 4-oxide (64) and its N-methyl derivative (65) condense with compoimds containing an active methylene group in the presence of piperidine, yielding 3-alkylated quinoxalinones (66). The oxide 64, when warmed with aqueous potassium cyanide, affords 3-cyano-l,2-dihydro-2-oxoquinoxaline, whereas oxide 65 gives l,2-dihydro-3-hydroxy-2-oxo-l-methylquinoxaline. ... 

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. " ... 

Methylquinoxaline reacts with both alkyl and aryl magnesium compounds to give, after hydrolysis, 2-alkyl-, or 2-aryl-l,2-dihydro-3-methylquinoxalines. When the dihydro compound 2, derived from p-tolylmagnesium bromide, is heated in ethanol, isomerization occurs, and... 

Preliminary ether formation followed by cyclisation to a benzofuran was achieved by reaction of 2-hydroxybenzaldehyde with a 2-haiogeno-methyl-3-methyiquinoxaline and treatment of the product, 2-(3-methyi-2-quinoxalinylmethoxy)benzaldehyde in ethanol with potassium hydroxide under reflux for 3 hours, to afford in 92% yield, 2-(3-methylquinoxalin-2-yl)benzofuran (ref.71). Alkylation occurs rather than condensation of the 3-methyi group with the o-formyl group. 

The influence of acid on these additions is considerable. In ethanol, for example, ethyl nicotinate is converted into the corresponding 6a-hydroxyethylpyridine, whereas in acidified solution the 6-ethylpyridine derivative is obtained.147 The function of the acid may, of course, simply be to promote dehydration of the intermediate 6a-hydroxyethyldihydropyridine. Phthalazine and quinoxaline are converted by irradiation in acidified methanol into 1-methylphthalazine and 2-methylquinoxaline, respectively.148 In this case, however, there is evidence to suggest that the alkylations proceed by way of electron transfer from the solvent to an excited state of the protonated diazines in neutral solution, a hydrogen... 

A range of secondary A-alkylanilines undergo oxidative olefination with 2-alkyl-quinoline, 4-methylquinoline, 1-methylisoquinoline, 2-methylquinoxaline, 2-methyl-quinazoline, 2-methylbenzo[fiG-thiazole, acetophenone, and malononitrile in DMF to form structurally diverse polysubstituted alkenes in moderate to excellent yields with excellent E Z >99 1 selectivity with the use of 2,3-dichloro-5,6-dicyano-l,4-benzoquinone as the oxidant. Mechanistically, the oxidative olefination reaction proceeds through amine oxidation followed by imine olefination." ii... 

---