| Identification | Back Directory | [Name]
1-chloro-2-iodo-4-nitro-benzene | [CAS]
74534-15-9 | [Synonyms]
Nsc223078
3-Iodo-4-chloronitrobenzene
1-chloro-2-iodo-4-nitro-benzene
Benzene, 1-chloro-2-iodo-4-nitro- | [EINECS(EC#)]
200-258-5 | [Molecular Formula]
C6H3ClINO2 | [MDL Number]
MFCD11521301 | [MOL File]
74534-15-9.mol | [Molecular Weight]
283.45 |
| Chemical Properties | Back Directory | [Melting point ]
78 °C | [Boiling point ]
315.7±22.0 °C(Predicted) | [density ]
2.094±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C(protect from light) | [solubility ]
Chloroform (Slightly), Methanol (Slightly) | [form ]
Solid | [color ]
Dark Yellow | [InChI]
InChI=1S/C6H3ClINO2/c7-5-2-1-4(9(10)11)3-6(5)8/h1-3H | [InChIKey]
LOQLBMYYBHCMJJ-UHFFFAOYSA-N | [SMILES]
C1(Cl)=CC=C([N+]([O-])=O)C=C1I |
| Hazard Information | Back Directory | [Uses]
1-Chloro-2-iodo-4-nitrobenzene is an intermediate for Vismodegib (V674700) and Vismodegib-d4 (V674702), pharmaceuticals that target the hedgehog (Hh) pathway. | [Synthesis]
1) Preparation of 1-chloro-2-iodo-4-nitrobenzene (Compounds 1-3)
2-Chloro-5-nitroaniline (40 g, 232.0 mmol) was dissolved in a mixed solution of concentrated sulfuric acid (32 mL) and water (320 mL) using mechanical stirring. The reaction solution was cooled to -5 °C and a solution of sodium nitrite (18.2 g, 0.26 mol) in water (69 mL) was added slowly and dropwise. The reaction mixture was stirred under ice bath conditions for 0.5 h. Subsequently, a solution of potassium iodide (69.3 g, 0.41 mol) in water (277 mL) was added slowly, controlling the reaction temperature to be below 5 °C. Stirring was continued for 3 hours. After completion of the reaction, it was extracted with ethyl acetate at 0 °C. The organic phases were combined, washed with saturated sodium thiosulfate (Na2S2O3) solution, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The residue was recrystallized by isopropanol/hexane (300 mL/100 mL) mixed solvent to give compounds 1-3 (38 g, 58% yield) as light tan crystalline solids.
1H NMR (400 MHz, CDCl3): δ 7.61 (d, J = 8.8 Hz, 1H), 8.16 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 8.70 (d, J = 2.8 Hz, 1H). | [References]
[1] Patent: WO2009/126863, 2009, A2. Location in patent: Page/Page column 87-88
[2] Patent: WO2012/76413, 2012, A1. Location in patent: Page/Page column 11
[3] Patent: EP2468726, 2012, A1. Location in patent: Page/Page column 6
[4] Organic Process Research and Development, 2012, vol. 16, # 11, p. 1739 - 1745
[5] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 14, p. 2399 - 2402 |
|
|