Quinoxaline diamino

Reaction of 2,3-dichloroquinoxaline 367 with sodium azide in ethanol has been used to synthesize bistetrazolo-[l,5- 5, l -c]quinoxaline 368 in 65% yield (Scheme 28) <1997JOC4082>. Similarly, reaction of 2,3-dichloroquinoxaline 367 with thiosemicarbazide 366 has been used to generate l,6-diamino-bis-l,2,4-triazolo[4,3- 3,4-f]quinoxaline 365 in 67% yield <2002AP389>. Condensation of cyclopropanecarboxylic acid hydrazide 369 meanwhile gives rise to the cyclopropyl-substituted tetracycle 370 in 93% yield in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base (Scheme 28) <2005JOC2878>. 

Reduction of 2-amino-3-nitrodibenzothiophene in the presence of acetic acid yields the imidazole (109) and by conducting this reaction in the absence of acetic acid 2,3-diaminodibenzothiophene should be readily accessible. A similar reduction of 3-amino-4-nitrodibenzothio-phene yields 3,4-diaminodibenzothiophene (60%). In addition to the typical reactions described above for the 1,2-diamino compound, 3,4-diaminodibenzothiophene condenses with benzil to give the quinoxaline... 

Azirines are dimerized under various conditions to dihydropyrazines or their dehydrogenated products, namely pyrazines (Section 8.03.9.5). Quinoxalines are oxidized with potassium permanganate to afford 2,3-pyrazinedicarboxylic acids, and pteridines are hydrolyzed to give 3-amino-2-pyrazinecarboxylic acid derivatives. Condensation of 3,4-diamino-l,2,5-thiadiazole 176 with a-diketones produces l,2,5-thiadiazolo[3,4- Jpyrazines 177, which are reduced to provide 2,3-diaminopyrazines 178 (Scheme 51) <1997JCM250>. 

Attention was then turned to aromatic heterocyclic ladder polymers other than BBL. Due to the complexities in their synthesis, ladder polymers were not reported extensively in the literature at that time. A sample of polyfluoflavine (I) having an inherent viscosity in methanesulfonic acid of 2.5 was obtained from professor C. S. Marvel at the University of Arizona. The ladder polymer was prepared [5] from the A-B polycondensation of 2,3-dihydroxy-6,7-diamino-quinoxaline hydrochloride in PPA. Transparent blue sheets were observed on precipitation of this polymer from methanesulfonic acid, and when collected and dried, it formed gold films much like the color of the BBL films. It was felt at that time that all ladder polymers of sufficient molecular weight would form precipitated films. 

The preparation of quinoxaline derivatives carrying a substituent in the benzene ring requires suitably substituted o-phenylenediamines. These have been prepared by reductive cleavage (SnCl2) of appropriately substituted 2,1,3-benzoselenadiazoles (I9).21 Benzo-selenadiazoles, readily prepared from 1,2-diaminobenzenes and selenium dioxide, undergo halogenation at positions 4 and 7 and sulfonation at C-4. 5,6-Dichloro- 2,3-diphenylquinoxaline has been synthesized from benzil and l,2-diamino-3,4-dichlorobenzene, the diamine in turn was obtained from 4,5-dichloro-2,l,3-benzoselenadiazole.22... 

The dimethyl-1,5-benzodiazepine 43 on attempted nitration with H2S04-HN03 at 0°-5° gave, by ring contraction, 2-acetyl-3-methyl-quinoxaline (26%), together with some of the AVV -diacetyl derivative of 1,2-diamino-4-nitro benzene.44... 

The same type of synthesis affords pyrazino[2,3-e]-1,2,4-triazines (329) and (330) from the diamino precursor (328), by reaction of the latter with glyoxal or phenylglyoxal, respectively. Product (329) is a dihydrate. The fully aromatic intermediate could not be isolated. Formation of (330) involves not only covalent solvation, but also an unusual TV-methylation of the presumed first-formed intermediate, and the suggested mechanism is outlined in Scheme 24 <86JHC33,93H(36)2577>. Reversing the order of polarities of the components allows [4 + 2] cyclization of pyrimidine (331) with orr/io-phenylenediamine (332), giving the benzo fused pyrazino[2,3-c][l,2,6]thiadiazine (333) (a [l,2,6]thiadiazino[3,4-6]quinoxaline]) (Equation (52)) <72ZN(B)1471>. 

Azole approach. 3,4-Diamino-l,2,5-thiadiazole reacts with 1,2-dicarbonyl compounds to form pyrazines (747) (76JHC13). From the reaction of 1,2,5-thiadiazole 1,1-oxides such as (748) with o-phenylenediamine, the l,3-dihydro[l,2,5]thiadiazolo[3,4-Z>]quinoxaline 2,2-dioxide (749) is formed. To understand this reaction it is pointed out that the 1,2,5-thiadiazole 1,1-dioxide ring is to be regarded as alicyclic rather than aromatic and is strongly 7r-electron deficient. Substituents with leaving properties in the 3,4-positions are therefore readily displaced as in the reaction of (748) (75JOC2743). 

Amino-6-nitro-Fischer s base (36, R = N02) was reduced to the 5,6-diamino compound (36, R = NH2) in 80% yield, which (as its hexachlorostannate salt) was condensed with benzoic acid and with benzil to give, respectively, a 68% yield of 5,7,7-trimethyl-6-methylene-6,7-dihydro-5 7/-pyrrolo[2,3-/]-benzimidazole (37) and a 62% yield of 6,8,8-trimethyl-7-methylene-2,3-diphenyl-7,8-dihydro-6 7/-pyrrolo[2,3-g]quinoxaline (38).42 Spiropyrans from these linearly annellated Fischer s bases were not reported they likely would color upon irradiation with blue light. 

Acridin 2,7-Diamino-9-oxo-9,10-dihydro- XI/1, 425 6H-(Azepino 3,4-b quinoxalin) 8-Methoxy- E16c, 184 (2-N3-Phenazin/NaOCHj) 3H,5H-(Benzo(i j]quinolizin) 1-Diazomethyl-3-oxo-6,7-dihydro-E14b, 1027... 

The condensation of a,/3-diamino compounds with a,/3-dicarbonyl compounds has been extensively used for the synthesis of quinoxaline (59) and pteridines (61) from o-phenylenediamine (58) and 4,5-diaminopyrimidines (60), respectively. 

Bredereck and Schmotzer (1044), from diaminomaleonitrile (DAMN hydrogen cyanide tetramer) and oxalyl chloride, prepared 2,3-dicyano-5,6-dihydroxy-pyrazine but Stetten and Fox (1049) could not prepare 23-diamino-5-hydroxy-pyrazine from glycine amide and oxamide. Section 11.3 lists preparations from a, -diamino or a, -diimino compounds and reagents other than a,0-dicarbonyl compounds (384) with additional data (1050) and oxidation of 23-dichloro-quinoxaline with hot aqueous potassium permanganate gave 23-dicarboxy-5,6-dihydroxypyrazine (1051). 

Quinoxaline (235) has been easily aminated in liquid ammonia with excess potassium amide and potassium permanganate as oxidant (82JHC1285). The ratio of monoamino to diamino products can be altered by varying the reaction time prior to addition of the oxidant (Scheme 78). When potassium permanganate was added 5-10 min after 235 was added to liquid ammonia containing potassium amide, the yield of 2-aminoquinoxaline (236) was 53% and 2,3-diaminoquinoxaline(237) was 23%. However, if the oxidant was not added until 30 min had elapsed, the yield of 236 was 4% and that of 237 was 57%. 

Quinoxaline-thiones (144) have been prepared by heating 1,2-diamino-benzene with a-halo-ketones (RCOCH2X), sulphur, and triethylamine in dimethyl sulphoxide. ... 

Substituted quinoxalines undergo some interesting reactions when treated with nucleophilic reagents. When 6-bromoquinoxaline is treated with potassium amide in liquid ammonia the main product is benzimidazole. Minor amounts of 2-amino- and 2,3-diaminoquinoxalines are also formed, but none of the expected 5- and 6-aminoquinoxalines are obtained (Scheme ) Similar treatment of 6-chloroquinoxaline gives a mixture of 2-amino-7-chloroquinoxaline and 6-chloro-2,3-diamino-quinoxaline. It has been suggested that the difference in behavior between the 6-bromo and 6-chloro compounds may be explained by the... 

There have been several reports of the hydrolysis of 2-aminoquinoxalines to quinoxalinones. For example, 2,3-diamino-quinoxaline is very readily hydrolyzed (2.5 M HCI, 100°, 5 min) to 3-aminoquinoxalin-2-one, and treatment of 2-amino-3-phenylquinoxaline with nitrous acid furnishes 3-phenylquinoxalin-2-one in excellent yield. ... 

Ch. 24 Preparation of Quinoxalines from Primary Aromatic o-Diamino and 1,3-Dicaibonyl Compounds... 

Recently, Kamitori reported a new procedure to synthesize fluorine-containing heterocycles including pyrazines and imidazoles <01JHC773>. Aldehyde-derived dialkylhydrazones 199 were treated with trifluoroacetic anhydride to give 200, which was then hydrolyzed with H2SO4 to afford 201, a-Diketohydrates 201 reacted readily with diamines such as diamino succinonitrile to afford pyrazines 202, or with 1,2-phenylencdiamine to yield quinoxalines 203 in good yields. 

Synthesis of b-SFs-quinoxalines was described by Beier and coworkers (12EJ02123) utihzing l,2-diamino-4-SF5-benzene (61) as a precursor for... 

Condensation of dehydro-D-isoascorbic acid (dehydro-D-erythorbic acid) with one or two equivalents of l,2-diamino-4,5-dimethyl-benzene afforded a quinoxalinone, e.g. 81 or a quinoxaline, e.g, 82, respectively. An isomer of flavin adenine dinucleotide containing a D-arabinitol-l-yl rather than a D-ribitol-l-yl moiety, has been identified as a naturally occurring co-factor of the alcohol oxidase of methanol utilizing yeasts. ... 

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