(±)-α-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol

cream-coloured to beige powder

In 1000ml of three necked flask equipped with a stirrer, thermometer, dropping funnel added 102g of 2, 4-dichloro-2-imidazole-acetophenone(0.4mol) , methanol 300ml, portion wise added potassium borohydride was slowly warmed to reflux, after incubated stirring for 1 h, TLC detection reaction (Ethylacetate: methanol 10:1 (ν / ν), the reaction was completed, vacuum recovery of methanol, Concentrated liquid pH was adjusted to ph 4-5 using 5percent of hydrochloric acid,  suction filtration , the filtratepH was adjusted to pH 7-8 with 5percent of sodium bicarbonate solution, there appears a white solid, it was suction filtrated , washwith darer , dried , recrystallized to obtain 1-(2, 4-dichlorophenyl)-2-imidazolethanol 93.1g. yield 90.5percent, mp. 34-135°C ;A solution of 15 3 (1mmol, 1eq) in 17 methanol (4ml) were added to a suspension of 16 sodium borohydride (2mmol, 1eq) in anhydrous methanol (20ml) while maintaining the temperature below 0°C. The resulting mixture was stirred at room temperature for 1h and then reflux the mixture for 1h until 3 disappeared. The reaction mixture was cooled to room temperature and 64 water was added. The 18 product was extracted with ethyl acetate (10ml×3). The combined organic phase was dried over NaNaBH4 (0.21 g, 5.5 mmol) was added (in three portions) to asolution of the ketone (1.4 g, 5.5 mmol) 8 in 2-propanol (25 mL) at3–5 C. The mixture was stirred at room temperature for 2 h (monitoredby TLC). Then, 50percent of solvent was removed under reducedpressure and 3percent solution of HCl (3 mL) was added. The reactionwas neutralized with sodium carbonate and poured into water.The mixture was extracted with ethyl acetate and the organicphase was dried over anhydrous Na2SO4. The solvent was removedunder reduced pressure on a rotary evaporator to yield a viscousgum, which was recrystallized in acetone to give 13. Yield:1.19 g, 85percent.(b) To a mixture of sodium hydride (0.080 g, 2 mmol) in 5 mL of DMF was added imidazole (0.136 g, 2 mmol) dissolved in 2 mL of DMF. General procedure: Asolution of halohydrins (1.0 equiv.) and ionic liquid 7 (1.0 equiv.)in anhydrous MeCN was refluxed for 10–12 h. The reaction hasbeen monitored by TLC. A 3=4 volume of solvent was removed undervacuum, the residue poured into water and extracted with ethylacetate. The organic phase was dried over anhydrous Na2SO4, distilledoff. The obtained crude product was precipitated in acetone as a white solid. Yield 68percent from 11. Yield 40percent from 12. M.p. 142–143 C. IR (KBr, cm 1): 1512 (m), 1079 (s), 845 (s), 733 (m). 1HNMR (DMSO-d6, ppm): d = 4.0–4.06 (m, 2 H, 2CH2), 5.06–5.08 (m, 1 H, 1CH), 4.16 (d, J = 10.8 Hz, 1 H, OH), 6.03 (d, J = 4 Hz, 1 H, 4CHof the imidazole ring), 6.83 (d, J = 4 Hz, 1 H, 5CH of the imidazolering), 7.03 (s, 1 H, 2CH), 7.42–7.46 (m, 2 H, 5CH, 6CH). 7.59 (s, 1H, 3CH). 13C NMR (DMSO-d6, ppm): d = 137.14 (6C), 136.20 (1C), 132.99 (10C), 130.11 (7C), 130.01 (2C), 129.68 (8C), 128.04 (11C), 126.12 (9C), 118.44 (3C) 63.88 (5C); 53.22 (4C). Anal. Calc. for C11-H10Cl2N2O (257.12): C, 51.38; H, 3.92; N, 10.89; Found C, 51.39;H, 3.92; N, 10.90percent.General procedure: Asolution of halohydrins (1.0 equiv.) and ionic liquid 7 (1.0 equiv.)in anhydrous MeCN was refluxed for 10–12 h. The reaction hasbeen monitored by TLC. A 3=4 volume of solvent was removed undervacuum, the residue poured into water and extracted with ethylacetate. The organic phase was dried over anhydrous Na2SO4, distilledoff. The obtained crude product was precipitated in acetone as a white solid. Yield 68percent from 11. Yield 40percent from 12. M.p. 142–143 C. IR (KBr, cm 1): 1512 (m), 1079 (s), 845 (s), 733 (m). 1HNMR (DMSO-d6, ppm): d = 4.0–4.06 (m, 2 H, 2CH2), 5.06–5.08 (m, 1 H, 1CH), 4.16 (d, J = 10.8 Hz, 1 H, OH), 6.03 (d, J = 4 Hz, 1 H, 4CHof the imidazole ring), 6.83 (d, J = 4 Hz, 1 H, 5CH of the imidazolering), 7.03 (s, 1 H, 2CH), 7.42–7.46 (m, 2 H, 5CH, 6CH). 7.59 (s, 1H, 3CH). 13C NMR (DMSO-d6, ppm): d = 137.14 (6C), 136.20 (1C), 132.99 (10C), 130.11 (7C), 130.01 (2C), 129.68 (8C), 128.04 (11C), 126.12 (9C), 118.44 (3C) 63.88 (5C); 53.22 (4C). Anal. Calc. for C11-H10Cl2N2O (257.12): C, 51.38; H, 3.92; N, 10.89; Found C, 51.39;H, 3.92; N, 10.90percent.

Intermediate in the preparation of Miconazole.An impurity in the synthesis of Fenticonazole.An impurity in the synthesis of Ketoconazole.

Molecular Weight:257.11
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:256.0170183
Monoisotopic Mass:256.0170183
Topological Polar Surface Area:38
Heavy Atom Count:16
Complexity:230
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes