Quinoxaline amino

Many pyrazine and quinoxaline syntheses yield mono- or di-N-oxides (76H(4)769). The condensation of a-aminooximes with 1,2-diketones results in the direct formation of pyrazine mono-N-oxides. The a-aminooximes themselves are not easily prepared but 2-amino-2-deoxy sugars readily form the oximes, which have been condensed with glyoxal to yield the pyrazine 4-oxides (Scheme 18) (72JOC2635, 80JOC1693). 

The progression from hydroxypyrazines/quinoxalines through the halo derivatives to the amines is a logical sequence in that, for practical purposes, this is the best method of synthesis of the amino compounds (see preceding Section). The ammonolysis proceeds most easily in the case of fluoro compounds. Fluoropyrazine reacts with aqueous ammonia at room temperature, whereas the reaction with chloropyrazine requires higher temperature and pressure. 

As might be expected from a consideration of electronic effects, an amino substituent activates pyrazines, quinoxalines and phenazines to electrophilic attack, usually at positions ortho and para to the amino group thus, bromination of 2-aminopyrazine with bromine in acetic acid yields 2-amino-3,5-dibromopyrazine (Scheme 29). 

All heterocyclic enamines readily undergo condensation with o-amino-benzaldehyde. The quinoxaline derivatives thus formed have a characteristic yellow color. Therefore, this reaction can serve as evidence of the presence of an enamine in plants (295,309). 

C. Preparation of Quinoxalines Using a-Amino Acid Intermediates 210... 

C. Phepaeation of Quinoxalines Using a-AMiNO Acid Intermediates... 

The nitration of 6-methoxyquinoxaline in concentrated sulfuric acid at 0°C gives 6-methoxy-5-nitroquinoxaline. The position of the nitro group is confirmed by reduction of the product to 5-amino-6-methoxy-quinoxaline identical with a sample prepared from 2,3,4-triamino-anisole and glyoxal ... 

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, ... 

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. ... 

Protonation of pyrazine A-oxides takes place at the unsubstituted ring nitrogen as revealed by examination of their UV spectra and ionization constants in water. The same holds for unsubstituted quinoxaline A-oxide and the 3-amino derivative. Pyrazine and quinoxaline di-A-oxides are protonated at one A-oxide oxygen atom (74KGS1554). 

Ester group of l-(ethoxycarbonylmethyl)-7-aryl-5-oxo-1,2,3,5-tetrahydro-pyrido[l,2,3-i/e]quinoxaline-6-carboxamides was hydrolyzed and the 1-carboxymethyl moiety was converted to an aminocarbonylmethyl group with 1-methylpiperazine (01MIP12). Bromo atom of l-(2-bromoacetyl) derivatives was substituted by different amines. An amino group in the side chain attached to the position 1 of 7-aryl-5-oxo-l,2,3,5-tetrahydropyr-ido[l,2,3-i/e]quinoxaline-6-carboxamides was acylated, and terc-butoxycarbonyl protecting group of amino group was eliminated. 

In a similar manner, bromination, dehydrobromination and amination of l-tosyl-l//-l-benz-azepin-3(2/7)-one yields the 2-amino-3//-l-benzazepin-3-one 10, which condenses with ben-zene-1,2-diamine to give 6//-l-benzazepino[2,3-6]quinoxaline (11).27... 

Benzenediamine (288) and the unstable oxamide equivalent (289), prepared in situ by chlorination of bis(dimethylamino)acetylene, gave 2,3-bis(dimethyl amino)quinoxaline (290) (no details). ... 

Chloro-3-methylquinoxaline 4-oxide gave 3-chloro-2-quinoxalinecarbalde-hyde 1-oxide (172) (SeOi, PhH, reflux, h 72%) dioxane may be used as solvent for such oxidations yielding, for example, 3-amino-2-quinoxaline-carbaldehyde ethyl acetate may also be so used. 

Chloro-3-phenylethynylquinoxaline (91) with dimethylamine gave 2-dimethyl-amino-3-phenylethynylquinoxaline (90) (H2O, reflux, 4h 58%), but with neat ethanolamine, it gave 2-(2-hydroxyethylamino)-3-[p-(2-hydroxyethyla-mino)styryl]quinoxaline (92) (20°C, 8 h 91% note addition of the primary... 

Me2NCHO, warm then substrate slowly, reflux, 3 h 83%) the same substrate (219) with 2-amino-3-pyridinol (220, X = N) gave 12//-pyrido-[2, 3 5,6]oxazino[2,3-/7]quinoxaline (221, X = N) (likewise 72%) " and analogs were made somewhat similarly. ... 

Bis(bromomethyl)quinoxaline and 4-amino-1,3,4-triazole-3(27/)-thione gave 2,3-bis(4-amino-l,2,4-triazol-3-ylthiomethyl)quinoxaline (281) (KOH, EtOH, 20°C reflux, 1 h 71% analogs likewise). ... 

Bis(bromomethyl)quinoxaline (296) gave either 6,8-dihydrofuro[3,4-g]qui-noxaline (297) (NaOH, H20-MeCN, BU4NHSO4, no further details 84%) or ethyl 7-isocyano-7,8-dihydro-6//-cyclopenta[g]quinoxaline-7-carboxylate (298) (Et02CCH2NC, K2CO3, BU4NHSO4, MeCN, no further details 38%) and thence the 7-amino ester (HCl-EtOH, no further details 90%). ... 

Methylquinoxaline 4-oxide (264) selectively from 2-methylquinoxaline 1,4-dioxide (265) (ascorbic acid, H2O, 90°C, 5 h 58% homologs likewise) the natural amino acids in foods can also reduce such quinoxaline N-... 

---