6-Methylquinoxaline

Elina and co-workers have extensively investigated the reactions of 2-methylquinoxaline 1,4-dioxide and 2,3 methylquinoxaline 1,4-dioxide with aldehydes. 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 l-oxide. ... 

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. 

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... 

Aminopyrazines and 2-aminoquinoxalines, like their pyridine analogs, react with nitrous acid under aqueous conditions to give the 2(l//)-pyrazinones and 2(l//)-quinoxalinones. 2-Aminoquinoxalines are more readily hydrolyzed than typical heterocyclic amines and 2-amino-3-methylquinoxaline, for example, undergoes hydrolysis on heating at 100 °C with dilute sodium hydroxide (59JCS1132). 

The structure of this compound is confirmed by the preparation of the 1-acetyl derivative, acid degradation to 4-methylquinoxalin-3-one-2-carboxylic acid (12), and alternative synthesis from the acid chloride of (12) and AW -dimethyluread A most unusual cyclization occurs when AW-dimethyl-o-phenylenediamine (15) is treated with alloxan in ethanolic solution this apparently involves an A-methyl group and leads to the formation of the spirobarbituric acid (16). The struc-... 

The bromination of 5,8-dimethoxyquinoxaline in methanol gives a mixture of 6-bromo and 6,7-dibromo compounds/ Treatment of 2-methylquinoxaline with bromine in acetic acid yields a mixture of 27% of 2 bromomethyl- and 37% of 2-dibromomethyl-quinoxaline." Thus in the absence of powerfully activating groups, side-chain rather than nuclear substitution takes place. 

Catalytic reduction of 2-acetyl-3-methylquinoxaline (29) in ethanol with 1 mole of hydrogen, gives a deep crimson solution, from which red-brown needles of 2-acetyl-l,4-dihydro-3-methylquinoxaline (30) are obtained. Ethanolic solutions of (30) reoxidize on exposure to air to 2-acetyl-3-methylquinoxaline, but the solid dye is stable in air for several days. Similar results are obtained with 2-acetyl-3-phenyl-quinoxaline (31), from the reduction of which a purple-red dye (32) is obtained. ... 

In boiling ethanol, under nitrogen and in the presence of palladized charcoal, 2-acetyl-l,4-dihydro-3-methylquinoxaline (30) undergoes dismutation to give a mixture of 2-acetyl-3-methylquinoxaline, 2-acetyl-l,2,3,4-tetrahydro-3-methylquinoxaline (33), and 2-l -hydroxy-ethyl-3-methylquinoxaline (34), The latter compound is the product of sodium borohydride or Meerwein-Ponndorf reduction of 2-acetyl-3-methylquinoxaline. 

Peracetic acid oxidation of l-methylquinoxalin-2-one (42) at 55°C gives l-methylquinoxaline-2,3-dione (43) in moderate yield, and similar treatment of l,3-dimethylquinoxalin-2-one (44) yields a small quantity of the 4-oxide, An improved yield of (43) is obtained by... 

Oxidation of 4-methylquinoxalin-3-one 2-carboxy-fV -methylamlide (45) with hydrogen peroxide and acetic acid furnishes the 1-oxide but, on removal of either or both of the fV-raethyl groups (giving 46, 47, or 48), oxidation with hydrogen peroxide or with peracetic or perbenzoic acid results in the removal of the carboxyamide groups and the formation of a quinoxaline-2,3-dione. ... 

Aminoquinoxaline 1-methiodide (65) is slowly formed when 2-aminoquinoxaline is treated with excess of methyl iodide in methanol at room temperature. Decomposition of the 1-methiodide with cold aqueous sodium hydroxide solution gives l-methylquinoxalin-2 one-imine (66) and this on hydrolysis yields l-methylquinoxalin-2-one. ... 

Aminoquinoxaline exists predominantly as such rather than in the tautomeric imino form. This is indicated by a comparison of the basic strength of the 2-amino compound (pKo 3.90) and those of its fixed methylated tautomers, 2-dimethylaminoquinoxaline pKa 3.72) and l-methylquinoxalin-2-oneimine (pfCn 8.70). The ultraviolet spectrum of the neutral molecule of 2-dimethylaminoquinoxaline shows the expected bathochromic shifts compared to that of 2-aminoquinoxaline these spectra differ from the ultraviolet spectrum of the neutral molecule of l-methylquinoxalin-2-oneimine (Fig. 1). The mono-cations (68) and (69) derived from 2-aminoquinoxaline and l-methylquinoxalin-2-oneimine have a similar chromophoric system and show almost identical ultraviolet absorption (Fig. 2). 

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-ones are in tautomeric equilibrium with 2-hydroxy-quinoxalines, but physical measurements indicate that both in solution and in the solid state they exist as cyclic amides rather than as hydroxy compounds. Thus quinoxalin-2-one and its A -methyl derivative show practically identical ultraviolet absorption and are bases of similar strength. In contrast, the ultraviolet spectra of quinoxalin-2-one and its 0-methyl derivative (2-methoxyquinoxaIine) are dissimilar. The methoxy compound is also a significantly stronger base (Table II). Similar relationships also exist between the ultraviolet absorption and ionization properties of 3-methylquinoxalin-2-one and its N- and 0-methyl derivatives. The infrared spectrum of 3- (p-methoxy-benzyl)quinoxalin-2-one (77) in methylene chloride shows bands at 3375 and 1565 cm" which are absent in the spectrum of the deuterated... 

Chromic acid oxidation of hydroxyiminomalon-bis-AT -methylanilide (93) gives 4-methylquinoxalin-3-one-2-carboxy-A -methylanilide 1-oxide (94) by a process involving AT -oxidation and dehydrative ring closure. ... 

The structure of the latter compound has been confirmed by alternative synthesis from 4-methylquinoxalin-3-one-2-carboxylic acid, which... 

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. ... 

The somewhat analogous substrate, p-methoxy-A-(2-nitroprop-l-enyl)aniline (15), afforded 6-methoxy-3-methylquinoxaline 4-oxide (16) (98% H2SO4 %). ... 

Benzenediamine (123, R = H) and 1-benzamido-1-chloroacetone gave 2-methylquinoxaline (126) (Na2C03, H20-EtOH, reflux, 6 h 70%) homologs likewise. °... 

Benzoxadiazole 1-oxide (473) gave 2-acetyl-3-methylquinoxaline 1,4-dioxide (472) (AC2CH2, NaOH, EtOH, 55°C, 90 min, then 20°C, 12 h 54% or AC2CH2 on Si02 gel, 20°C, 7 days 58%), 2-benzoyl-3-methylquinoxaline 1,4-dioxide (474) (BZCH2AC on 3A molecular sieve,... 

BzCH2C(=0)CH2Ph, neat EtjN, 20°C, 24 h 21%) ° 5,6-Difluoro-2,l,3-benzoxadiazole 1-oxide (476) gave 2-acetyl-6,7-difluoro-3-methylquinoxaline 1,4-dioxide (477) (AC2CH2, neat Et3N, 5°C, 1 h, then 20°C, 1 h 72% analogs likewise). ° = ... 

Benzoxadiazole 1-oxide (481) with 3-acetyltetrahydro-2-furanone (2-acetyl-butyrolactone 482) gave 2-(2-hydroxyethyl)-3-methylquinoxaline 1,4-diox-ide (483) (KOH, MeOH-HaO, 20°C, 24 h 50%) but with 2-acetylacetaldehyde dimethyl acetal (484), in the presence of morpholine as base, it gave 2-(2-morpholinovinyl)quinoxaline 1,4-dioxide (485) (PhH, reflux, water separation, 9 h 47%) ... 

Methylquinoxaline with phenyUithium gave a separable mixture of 2-methyl-3-phenylquinoxaline (45), 2-methyl-3-phenyl-3,4-dihydroquinoxaline (46), and 2-methyl-2,3-diphenyl-1,2,3,4-tetrahydroquinoxaline (47) [PhLi (made in situ), Et20, <20°C, 90 min 20%, 45%, and 35%, respectively). 

Chloro-3-methylquinoxaline and 2-cyanomethylpyridine gave 2-[a-cyano-a-(pyridin-2-yl)methyl]-3-methylquinoxaline (56) (K2CO3, MeaNCHO, reflux,... 

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