Isolation and identification of the intermediates during pyrazole formation of some carbohydrate hydrazone derivatives

• Published in: Carbohydrate research Vol. 326; no. 1; pp. 34 - 42
• Main Author: Awad, Laila F
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 19.05.2000; Elsevier
• Subjects: 2,3-Dihydrofuro[2,3- b]quinoxaline; 2,4,6-Trichlorophenylhydrazone; [But-2-en-1-yl]quinoxalin-2(1 H)one; Biochemistry & Molecular Biology; Carbohydrates - chemical synthesis; Carbohydrates - chemistry; Cell Line; Cell Survival - drug effects; Chemistry; Chemistry, Applied; Chemistry, Organic; Hepatitis B virus - drug effects; Humans; Hydrazones - chemical synthesis; Hydrazones - chemistry; l-Ascorbic acid; Life Sciences & Biomedicine; Oxidation-Reduction; Physical Sciences; Pyrazole; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazolo[2,3- b]quinoxaline; Quinoxalin-2(1 H)one; Quinoxalines - chemistry; Quinoxalines - isolation & purification; Quinoxalines - pharmacology; Science & Technology; Virus Replication - drug effects; 2,4,6-Trichlorophenylhydrazone; l-Ascorbic acid; 2,3-Dihydrofuro[2,3- b]quinoxaline; Pyrazolo[2,3- b]quinoxaline; Quinoxalin-2(1 H)one; Pyrazole; [But-2-en-1-yl]quinoxalin-2(1 H)one; L-ascorbic acid; ACID; ANALOGS; 2,4,6-trichlorophenylhydrazone; 2,3-dihydrofuro[2,3-b]quinoxaline; [but-2-en-1-yl]quinoxalin-2(1H)one; pyrazole; pyrazolo[2,3-b]quinoxaline; CONFORMATIONAL-ANALYSIS; quinoxalin-2(1H)one
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/S0008-6215(00)00019-7

Reaction of the oxidation product of l-ascorbic acid, dehydro- l-ascorbic acid, with o-phenylenediamine, followed by 2,4,6-trichlorophenylhydrazine ( 3) afforded 3-[1-(2,4,6-trichlorophenylhydrazono)- l- threo-2,3,4-trihydroxybut-1-yl]quinoxalin-2(1 H)one ( 4), whose structure was deduced from studying its periodate oxidation, which gave the glyoxal derivative 3-[1-(2,4,6-trichlorophenylhydrazono)glyoxal-1-yl]quinoxalin-2(1 H)one ( 5) that upon reduction afforded 3-[1-(2,4,6-trichlorophenylhydrazono)-2-hydroxyethy-1-yl]quinoxalin-2(1 H)one ( 6). The reaction of 5 with 3 afforded the bishydrazone 3-[1,2-bis(2,4,6-trichlorophenylhydrazono)glyoxal-1-yl]quinoxalin-2(1 H)one. The reaction of 5 with acetic anhydride in pyridine afforded the 2,3-dihydrofuro[2,3- b]quinoxaline derivative 2-acetoxy-3-[2-acetyl-2-(2,4,6-trichlorophenyl)hydrazono)]-2,3-dihydrofuro[2,3- b]quinoxaline. Acetylation of 4 with acetic anhydride in pyridine afforded the acyclic diacetate intermediate 3-[3,4-di- O-acetyl-2-deoxy-1-(2,4,6-trichlorophenylhydrazono)but-2-en-1-yl]quinoxalin-2(1 H)one ( 12), which was also obtained from the reaction of 4 with boiling acetic anhydride. Compound 12 rearranged under the reaction conditions to give the pyrazole derivatives 3-[5-(acetoxymethyl)-1-(2,4,6-trichlorophenyl)pyrazol-3-yl]quinoxalin-2(1 H)one ( 14) and 2-acetoxy-3-[5-(acetoxymethyl)-1-(2,4,6-trichlorophenyl)pyrazol-3-yl)]quinoxaline ( 15), as well as the 2,3-dihydrofuro[2,3- b]quinoxaline derivative 2-(2-acetoxyethen-2-yl)-3-[2-(2,4,6-trichlorophenyl)hydrazono]-2,3-dihydrofuro[2,3- b]quinoxaline. Acetylation of 3-[5-(hydroxymethyl)-1-(2,4,6-trichlorophenyl)pyrazol-3-yl]quinoxalin-2(1 H)one ( 16) with acetic anhydride in pyridine or 12 with boiling acetic anhydride afforded 15 and 16, respectively. Treatment of 4 with diluted sodium hydroxide afforded the pyrazolo[2,3- b]quinoxaline (flavazole) derivative 1-(2,4,6-trichlorophenyl)-3-( l- threo-glycerol- 1-yl)pyrazolo[2,3- b]quinoxaline whose acetylation afforded the acetyl derivative 3-(2,3,4-tri- O-acetyl- l- threo-glycerol-1-yl)-1-(2,4,6-trichlorophenyl)pyrazolo[2,3- b]quinoxaline. The assigned structures were based on spectral analysis. The activity of compound 4 against hepatitis B virus has been studied.