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Letters in Organic Chemistry
Volumn 5, Issue 1, 2008, Pages 8-10
A new methodology to prepare 2-halogenoimidazoles via a N-THP protection
Author keywords

Halogenation; Imidazole; Lithiation; THP
Indexed keywords

EID: 38949194300     PISSN: 15701786     EISSN: None     Source Type: Journal    
DOI: 10.2174/157017808783330252     Document Type: Article
Times cited : (4)
References (15)
  • 1
  • 6
    • 33744790585 scopus 로고    scopus 로고
    • Gérard, A.-L.; Bouillon, A.; Mahatsekake, C.; Collot, V.; Rault, S. Tetrahedron Lett., 2006, 47, 4665; b unpublished results.
    • a) Gérard, A.-L.; Bouillon, A.; Mahatsekake, C.; Collot, V.; Rault, S. Tetrahedron Lett., 2006, 47, 4665; b) unpublished results.
  • 10
    • 38949184889 scopus 로고    scopus 로고
    • Synthesis of 1-THP-imidazole (3, To a slurry of sodium hydride 60% in oil (35.25 g, 881 mmol) in dry THF (400 mL) at 0°C under argon, was slowly added imidazole (20 g, 294 mmol, After 30 min of stirring at this temperature, a solution of 2-chlorotetrathydropyrane [8, 53.13 g, 440mmol) dissolved in 50 mL of dry THF was added dropwise. After this addition, the reaction was then stirred at room temperature for 4 h. The excess of NaH was hydrolysed with ice at 0°C. The mixture was extracted with ether, dried over magnesium sulfate and concentrated under reduced pressure. The resulting crude oil was purified by vacuum distillation (Bp 85°C at 0.05 mmHg) to provide the title compound (3, 33.23 g, 85, as a white solid. mp= 42°C 1H NMR (400 MHz, CDCl3, δ=7.65 (s, 1H, 7.08 (s, 1H, 7.05′(s, 1H, 5.20 (dd, J=2.6 and 9.5 Hz, 1H, 4.05-4.02 (m, 1H, 3.68-3.62 (m,1H, 2.01-1.89 (m, 3H, 1.69-1.60 (m, 3H, 13C NMR 100 MHz, C
    • 13C NMR (100 MHz, CDCI,): δ=135.5, 129.2, 116.7, 83.9, 67.7, 31.3, 24.7, 22.3.
  • 11
    • 38949156530 scopus 로고    scopus 로고
    • Typical Procedure for Obtention of 2-Halogeno-1-THP-imidazoles (4a-c, To a stirred solution under N2 of 1-THP-imidazole (122 mmol, 1&.5 g) in dry THF (300 mL) was added dropwise at -78°C 2.5 M n-BuLi (146 mmol, 58.5 mL, and kept under stirring during 25′ min. Hexachloroethane (183 mmol, 43.3 g) in dry THF (150 mL) was slowly added to the mixture over 15 min which was stirred at -78°C for 1.5 h before to be allowed to warm slowly to r.t After 1 h at r.t. the mixture was quenched with saturated aqueous NaHCO2, 50 mL) and extracted 3 times with CH2Cl2. The organic layer was dried with MgSO4 and concentrated. Purification by vacuum distillation afford (4a, 17.19g, 79, as white solid; mp, 40°C. 1H NMR (400 MHz, CDCl3, δ=7.12 (d, J=1.5 Hz, 1H, 6.96 (d, J=1.7 Hz, 1H, 5.27 (dd, J=2.2 and 10.2 Hz, 1H, 4.12-4.09 (m, 1H, 3.71-3.64 m,1H, 2.05-1.60
    • 3): δ=132.4, 119.8, 89.7, 86.3, 68.7, 31.6, 24.7, 22.9. HRMS: m/z calcd: 277.9916; found: 277.9917.
  • 12
    • 38949142245 scopus 로고    scopus 로고
    • Typical Procedure for Obtention of 2-Halogenoimidazoles (5a-c, To a solution of 2-Chloro-1-THP-imidazole (5.4 mmol, 1.0 g) in EtOH (5 mL) was added ethanolic HCl (5 mL) before to be refluxed for 45 min. After cooling, the mixture was neutralized with aqueous NaHCO3 and extracted 3 times with EtOAc. The organic layer was dried with MgSO4 and concentrated. The crude product was washed with Et2O and filtration afforded 2-Chloroimidazole (5a) as a white solid (0.44 g, 80, mp 170°C (Lit, 2] mp 166-167°C, 1H NMR (400 MHz, DMSO-d6, δ= 12.64 (sl, 1H, N-H, 7.00 (s, 2H, 5b, white solid (yield= 86, mp 202°C (Lit.2 mp 197-198°C, 1H NMR (400 MHz, DMSO-d6; δ= 12.76 (sl, 1H, N-H, 7.11 (s, 2H, 5c, slightly yellow solid (yield= 86, mp 208°C (Lit2 mp 190-192°C, 1H NMR 400 MHz, DMSO-d6, δ=12.59
    • 6); δ=12.59 (sl, 1H, N-H), 7.01 (s, 2H).
  • 15
    • 38949145656 scopus 로고    scopus 로고
    • Crystallographic data for the structural analysis have been deposited with the Cambridge Crystallographic Data Centre, publication number: CCDC 655277
    • Crystallographic data for the structural analysis have been deposited with the Cambridge Crystallographic Data Centre, publication number: CCDC 655277.

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