Quinoxalines with ring opening

Initial nucleophilic attack and ring opening are involved in the conversion of benzofuroxans into quinoxaline di-iV-oxides by treatment with imines, enamines, carbonyl compounds and active methylene compounds (354 — 355) (Section 3.4.1.10.1). 

The transformations of bis(triazole)-fused benzothiadiazepine 40 (Scheme 4) on treatment with -BuLi depended on the reaction temperature at —40°C, the sulfur extrusion occurred to afford fully aromatized bis(triazolo)quinoxaline 41, whereas at — 80°C, a seven-membered ring opening took place with formation of bis(triazolyl)benzene 42 <2002MC131>. 

Syntheses of 5,12-dioxocyclams containing the quinoxaline nucleus have utilized the ring opening of both rings of 3,3,6-trimethyl-l-azapenam 148. Treatment of 148 with acid gave the cyclam (Equation 16) after reduction of the imine. Unfortunately, this and related cyclams and their nickel complexes showed little useful biological activity in their interaction with DNA <2003JOC4179>. 

Quinoxalin-2(li/)-one undergoes ring opening on treatment with refluxing 50% aqueous hydrazine to yield a mixture of 2-methyl-l//-benzimidazole (10) and benzene-1,2-diamine (11). 

Ring opening of epoxy aldehydes or epoxy esters by a diamine at room temperature yields a 2-hydroxymethylquinoxaline. For epoxy esters, heating with lithium hydroxide is necessary and a 3-hydroxymethyi-2-quinoxaIinone is formed in good-to-excellent yields [3335]. The chemistry of quinoxalines has been reviewed [3459]. 

Dipolar cycloaddition of 4-phenylquinazoline 1-benzoylimine (50) and 1-phenylphthalazine 3-benzoylimines (54) with dimethyl acetylenedicar-boxylate gives primary 1 1 cycloadducts 72 and 73, whereas 3-phenyl-quinoxaline 1-benzoylimine (51) affords a product 74 which is formed by ring opening of a primary adduct.177 4-Ethyl-3-methylcinnoline 1-ethoxy-carbonylimine also gives ring-opened products 75 and 76.188... 

The 2-hydroxy-3-oxo-2,3-dihydrofuran 5 reacts with o-phenylene-diamine to give the quinoxaline-2-carboxylic acid ester 7. In this case the reaction may be envisaged as proceeding through the ring-opened tautomer (6) of the dihydrofuran/... 

Reduction of the benzimidazole derivatives 136 with lithium aluminum hydride gave the pyrrolo[2,3- ]quinoxalines 138 by way of the ring-opened intermediates 137. ... 

The same group of Japanese authors studied the photochemical reaction of fluorinated quinoxalines. Photochemical cycloadditions with quinoxaline derivative 1294 occurred and C=N double of the diazine ring, leading to the formation of azetidine derivatives (Scheme 299). The presence of trifluoromethyl group in the molecule of 1294 activated the substrate towards cycloaddion, so that even electron-deficient methyl methacrylate was introdnced in the reaction [797], In the case of ethyl vinyl ether as the alkene, the addnct 1296 also as in a case with 1289 was not stable and underwent azetidine ring-opening npon action of the solvent. Ketene was also successfully introduced in [2+2] cycloaddition with trifiuoromethyl-substituted quinoxaline derivatives [797]... 

Samsonov VA (2007) Furazan ring opening upon treatment of benzofurazan with ethanolamine to yield quinoxalines. Russ Chem Bull, hit Ed 5(12) 2510-2512... 

It was projxjsed that the quinoxahne residue of the product 100a was formed by the initial nucleophilic attack on position 4 and 5 of tetrachloropyridazine 98 by 1,2-DAB, then the aerial oxidation, giving an intermediate 1,4-dichloropyridazino [4,5-Z ]quinoxaline 101 which might react with two more molecules of 1,2-DAB to give the pyridazine-ring-opened system 100a (Scheme 6.32). 

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