4-HYDROXYINDAZOLE

White to off-white solid

C. 4-Aminoindazole (9.6 grams, 0.072 moles) was dissolved into a glass reaction vessel containing 7.2 grams of concentrated sulfuric acid in 75 mL water. This was sealed into a stainless steel autoclave and heated to 170 degrees C. overnight. The reaction mixture contained much black precipitate. The reaction mixture was diluted with ethyl acetate and water into a separatory funnel and partitioned. The aqueous layer was extracted several times with ethyl acetate until all the product was out of the aqueous fraction. The combined organic fractions were washed with brine, dried with magnesium sulfate, filtered, and concentrated to a dark brown or black oil. The product was purified by passing it over a silica pad with 50percent ethyl acetate/hexane mixture resulting in an off-white solid (3.3 grams, 33percent yield).Acetic anhydride (16.4 ml, 174 mmol), tetrabutylammonium bromide (933 mg, 2.90 mmol), potassium acetate (11.4 g, 116 mmol) and isoamyl nitrite (11.7 ml, 86.9 mmol) were added to a solution of 3-(acetylamino)-2-methylphenyl acetate (12.0 g, 57.9 mmol) in ethyl acetate (120 ml) at room temperature, and the resulting mixture was refluxed for 7 hours. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate = 3/1). Subsequently, the residue purified was dissolved in methanol (50 ml) and a 2N-aqueous sodium hydroxide solution (47.9 ml) was added thereto at room temperature and stirred for 1 hour. The methanol was distilled off under reduced pressure, and the resulting aqueous solution was adjusted to pH 4 to 5 by dropwise addition of hydrochloric acid and then extracted with acetic acid. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate = 2/1) to obtain 1H-indazol-4-ol (3.62 g, 47percent).1H-NMR (DMSO-d6) δ; 6.36 (1H, d, J=7.9Hz), 6.92 (1H, d, J=7.9Hz), 7.19 (1H, dd, J=7.9, 7.9Hz), 8.01 (1H, s), 10.00 (1H, s), 12.85 (1H, brs).C. Preparation of 4-Hydroxyindazole From 4-Aminoindazole 4-Aminoindazole (9.6 grams, 0.072 moles) was dissolved into a glass reaction vessel containing 7.2 grams of concentrated sulfuric acid in 75 mL water. This was sealed into a stainless steel autoclave and heated to 170 degrees C overnight. The reaction mixture contained much black precipitate. The reaction mixture was diluted with ethyl acetate and water into a separatory funnel and partitioned. The aqueous layer was extracted several times with ethyl acetate until all of the product was out of the aqueous fraction. The combined organic fractions were washed with brine, dried.with magnesium sulfate, filtered, and concentrated to a dark brown or black oil. The product was purified by passing it over a silica pad with a 50% ethyl acetate/hexane mixture, resulting in an off-white solid (3.3 grams, 33% yield).4-Aminoindazole (9.6 grams, 0.072 moles) was dissolved into a glass reaction vessel containing 7.2 grams of concentrated sulfuric acid in 75 mL water. This was sealed into a stainless steel autoclave and heated to 170 degrees C. overnight. The reaction mixture contained much black precipitate. The reaction mixture was diluted with ethyl acetate and water into a separatory funnel and partitioned. The aqueous layer was extracted several times with ethyl acetate until all the product was out of the aqueous fraction. The combined organic fractions were washed with brine, dried with magnesium sulfate, filtered, and concentrated to a dark brown or black oil. The product was purified by passing it over a silica pad with 50% ethyl acetate/hexane mixture resulting in an off-white solid (3.3 grams, 33% yield).

Molecular Weight:134.14
XLogP3:1.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:134.048012819
Monoisotopic Mass:134.048012819
Topological Polar Surface Area:48.9
Heavy Atom Count:10
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes