Imidazole-4-carboxaldehyde

White to light yellow powder

To a solution of 4-bromo-1H-imidazole (0.65 g, 4.4 mmol, 1.0 equiv.) indry THF (20 mL) at 0 C was added a 2 M solution of i-PrMgCl in THF (2.2 mL, 4.4 mmol, 1.0 equiv.)during 5 min. The clear solution was stirred at that temperature for an additional 5 min, and a2.5 M solution of n-BuLi in hexanes (3.5 mL, 8.8 mmol, 2.0 equiv.) was added dropwise during5 min, while maintaining the temperature below 20 C. The resulting mixture was stirred at thattemperature for 0.5 h, dry DMF (0.32 g, 4.4 mmol, 1.0 equiv.) was added to 20 C. The resultingmixture was warmed to 20 C in 0.5 h and quenched with water (6 mL). After stirring the mixturebelow 20 C for 10 min, the phases were separated and the water phase was extracted one additionaltime with ethyl acetate. The resulting suspension was allowed to reach room temperature and ®teredthrough a 0.5 1 cm pad of silica gel eluted with 10 mL of ethyl acetate. The ®ltrate was concentratedand the residue was puri®ed by ash chromatography on silica gel (eluent:petroleum ether/ethylacetate = 10:1) to afford product 3l as off-white solid, 0.36 g (yield: 85percent), m.p.: 175–177 C. 1H-NMR(600 MHz, DMSO) 9.74 (s, 1H), 7.99 (s, 1H), 7.94 (s, 1H). 13C-NMR (151 MHz, DMSO) 184.46, 139.44, 134.9, 129.5.Reference Example 10Under nitrogen stream, to ( 1R, 2S, 3R) -1- (2-sulfanyl-lH- imidazol-4-yl) butane-1, 2, 3, 4-tetraol (10 g, 45.4 mmol) was added water (40 mL) , and to the obtained suspension was added dropwise an aqueous diluted solution- of 30percent aqueous hydrogen peroxide (15.4 g, 136 mmol, 3.0 equivalents) in water (40 mL) over 10 min at 17 to 43°C (the compound was gradually dissolved to give an uniform pale-yellow solution) . The reaction mixture was stirred at 24 to 36°C for 4 hr, and barium carbonate (27 g, 136 mmol, 3.0 equivalents) was added over 5 min at 24 to 26°C (neutralized to pH 7), and the mixture was stirred at 25 to26°C for 1 hr and 20 min. The insoluble material was filtered off, and washed with water (40 mL) . To the filtrate and washing was added sodium sulfite (11.4 g, 90.8 mmol, 2.0 equivalents) over 5 min at 20 to 32°C. The obtained aqueous solution was stirred at 26 to 32°C for 1 hr and 30 min to give an aqueous solution of (1R, 2S, 3R) -1- (lH-imidazol-4-yl) butane- 1 , 2 , 3 , 4-tetraol . To this aqueous solution was added sodium periodate (29.1 g, 136 mmol, 3.0 equivalents) over 10 min at 12 to 30°C, and the mixture was stirred at 27 to 30°C for 1 hr and 30 min. To the reaction mixture was added sodium periodate(2.91 g, 13.6 mmol, 0.3 equivalents) at 27 to 30°C, and the mixture was stirred at 27 to 30°C for 2 hr. The insoluble material was filtered off, and washed four times with water (10 mL) . To the filtrate and washing was added methanol (500 mL) , and the inorganic salt was filtered off, and washed twice with methanol (50 mL) . To the filtrate and washing was added activated carbon (3 g, SHIRASAGI A, trade name), and the mixture was stirred at room temperature for 1 hr. Theinsoluble material was filtered off, and washed with methanol. The filtrate and washing were concentrated under reduced pressure to give a crude compound (9.37 g) . To the crude compound were added water (3 mL) and seed crystals forcrystallization, and the mixture was stirred at roomtemperature for 24 hr, and then for 2 hr under ice-cooling. The crystals were collected by filtration-, washed with cooled water (1 mL) , and vacuum-dried (50°C) to a constant amount to give (5) -formylimidazole (2.35 g) . yield 54percent.

4-Imidazolecarboxaldehyde is a 4-formyl derivative of imidazole used in the preparation of C17,20-lyase inhibitor for the treatemnet of androgen-dependent prostate cancer. 4-Imidazolecarboxaldehyde is also used in the synthesis of other biologically active compounds such as antimalarial drugs.

Molecular Weight:96.09
XLogP3:-0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:96.032362755
Monoisotopic Mass:96.032362755
Topological Polar Surface Area:45.8
Heavy Atom Count:7
Complexity:74.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes