4-(4-(4-Nitrophenyl)-1-piperazinyl)phenol Chemical Properties

Melting point:

>90°C (dec.)

Boiling point:

540.8±50.0 °C(Predicted)

Density 

1.317±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

DMSO (Slightly, Heated)

pka

12.18±0.30(Predicted)

form 

Solid

color 

Yellow to Brown

InChI

InChI=1S/C16H17N3O3/c20-16-7-5-14(6-8-16)18-11-9-17(10-12-18)13-1-3-15(4-2-13)19(21)22/h1-8,20H,9-12H2

InChIKey

BNHYDULILNJFFY-UHFFFAOYSA-N

SMILES

C1(O)=CC=C(N2CCN(C3=CC=C([N+]([O-])=O)C=C3)CC2)C=C1

CAS DataBase Reference

112559-81-6(CAS DataBase Reference)

4-(4-(4-Nitrophenyl)-1-piperazinyl)phenol Usage And Synthesis

Uses

4-[4-(4-Nitrophenyl)-1-piperazinyl]phenol is a key intermediate in the synthesis of triazole medicines, such as itraconazole (I937500), which are used in curing deep department fungal infections. Inhibitor of endothelial cell proliferation.

Synthesis

Under nitrogen protection, 420 g (2.36 mol) of 4-(1-piperazinyl)phenol, 520.6 g (3.30 mol) of 4-chloronitrobenzene, and 457.5 g (3.54 mol) of N,N-diisopropylethylamine (Huenig's base) were suspended in 1260 mL of N-methylpyrrolidone. The mixture was heated to 120-125°C until a clarified solution was formed. This temperature was maintained and the progress of the reaction was monitored by HPLC. Upon completion of the reaction (5-7 hr), the reaction solution was cooled to 75-80°C. 6.3 L of isopropanol was slowly added to the reaction mixture over a period of about 30 min while maintaining the temperature at 75-80°C (with slight heating if necessary). At the end of the addition, the product began to precipitate as yellow crystals. The suspension was cooled to 20-25°C and stirred at this temperature overnight. Subsequently, the suspension is further cooled to -10 to -5°C and stirred for 30 minutes. The product was collected by filtration and washed sequentially with 1.7 L of isopropanol and 5 x 840 mL of warm water (35-40°C). Finally, the product was dried under vacuum at 50°C (accompanied by a slight stream of nitrogen) to constant weight. The yield was 96% and the purity as determined by HPLC was 93%, which corresponded to the standard.

References

[1] Journal of Medicinal Chemistry, 2016, vol. 59, # 8, p. 3635 - 3649
[2] Patent: EP1230231, 2005, B1. Location in patent: Page/Page column 4
[3] Journal of Medicinal Chemistry, 2011, vol. 54, # 20, p. 7363 - 7374
[4] Patent: WO2018/45106, 2018, A1. Location in patent: Paragraph 00131
[5] Patent: WO2018/45104, 2018, A1. Location in patent: Paragraph 00156

4-(4-(4-Nitrophenyl)-1-piperazinyl)phenol(112559-81-6)Related Product Information

• Posaconazole Impurity 43
• O-Benzyl Posaconazole
• Posaconazole Impurity 50
• 1-(4-Methoxyphenyl)-4-(4-nitrophenyl)piperazine
• Phenol Red
• 4-tert-Butyl-2-nitrophenol
• 1-Phenyl-2-nitropropene
• Phenol
• 2-Phenylphenol
• 4-Nitrophenol
• 3-Aminophenol
• 2-Aminophenol
• PHENYL {4-[4-(4-HYDROXYPHENYL)PIPERAZIN-1-YL]PHENYL}CARBAMATE
• 1-[1-(Bromomethyl)ethenyl]-2,4-difluoro-benzene
• Posaconazole Impurity 64
• Hydrazine, [1-ethyl-2-(phenylmethoxy)propyl]-,[S-(R*,R*)]-(9CI)
• 1-(4-Methoxyphenyl)piperazine
• 2-[(1S,2S)-1-ethyl-2-bezyloxypropyl]-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]- 3H-1,2,4-Triazol-3-one