1-chloro-2-iodo-4-nitro-benzene Chemical Properties

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

Safety Information

HazardClass 

IRRITANT

HS Code 

2904990090

1-chloro-2-iodo-4-nitro-benzene Usage And Synthesis

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