4,4'-Difluorobenzhydrylpiperazine Chemical Properties

Melting point:

88-92 °C(lit.)

Boiling point:

130 °C

Density 

1.1462 (estimate)

vapor pressure 

0.001-0.003Pa at 20-25℃

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

solubility 

soluble in Methanol,Toluene

pka

9.00±0.10(Predicted)

form 

Crystalline Powder

color 

White to yellow

Water Solubility 

0.34 g/L (20 ºC)

BRN 

620754

Stability:

Hygroscopic

InChI

InChI=1S/C17H18F2N2/c18-15-5-1-13(2-6-15)17(21-11-9-20-10-12-21)14-3-7-16(19)8-4-14/h1-8,17,20H,9-12H2

InChIKey

TTXIFFYPVGWLSE-UHFFFAOYSA-N

SMILES

N1(C(C2=CC=C(F)C=C2)C2=CC=C(F)C=C2)CCNCC1

LogP

3.3-3.5 at pH7-11

CAS DataBase Reference

27469-60-9(CAS DataBase Reference)

Safety Information

Hazard Codes 

T

Risk Statements 

25-36/37/38

Safety Statements 

26-45-36/37/39

RIDADR 

UN 2811 6.1/PG 3

WGK Germany 

3

F 

10-34

Hazard Note 

Toxic

HazardClass 

IRRITANT

HazardClass 

6.1

PackingGroup 

III

HS Code 

29335990

MSDS

• Language:English Provider:1-(4,4'-Difluorobenzhydryl)piperazine
• Language:English Provider:SigmaAldrich
• Language:English Provider:ACROS

4,4'-Difluorobenzhydrylpiperazine Usage And Synthesis

Chemical Properties

white to yellow crystalline powder

Uses

1-Bis(4-fluorophenyl)methyl piperazine may be used to synthesize 1-[bis(4-fluorophenyl)methyl]-4-[3-[(N-ethoxycarbonyl-N-phenyl)amino]-2-hydroxypropyl]piperazine and (R, S) 3-[4-(bis(4-fluorophenyl)methyl)piperazin-1-yl]dihydrofuran-2(3H)-one.

General Description

1-Bis(4-fluorophenyl)methyl piperazine is formed during the synthesis of flunarizine. Its crystals exhibits monoclinic crystal system and space group P2₁/c.

Synthesis

GENERAL METHODS: NaBH4 (0.6 mol) was added batchwise to a stirred solution of benzophenone (1.0 mol) in methanol (2 vol) for 45 min at room temperature. The reaction mixture was stirred at ambient temperature for 2-3 h (the progress of the reaction was monitored by TLC), followed by dilution with water (750 mL) and adjusting the pH with acetic acid to 4. Extraction was carried out with dichloromethane (2 x 400 mL), the organic layer was washed with water (200 mL), dried with anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure to afford the pure benzophenol derivative as a white to off-white solid The yield was 93-97%. To a solution of diphenylmethanol derivative (1.0 mol) in toluene (370 mL) at room temperature, concentrated HCl (35% aqueous solution, 370 mL) and tetrabutylammonium bromide (0.01 mol) were added while stirring. The mixture was stirred continuously at 40-45 °C for 6-7 hours. After completion of the reaction (confirmed by TLC), it was cooled to room temperature. The organic layer was separated and concentrated under vacuum to give the crude diphenylmethyl chloride derivative as a light brown liquid in 95-97% yield. To a solution of diphenylmethyl chloride derivative (0.96 mol) in toluene (380 mL) at 60-70°C, anhydrous piperazine (5.0 mol) was slowly added over 45-60 minutes. The resulting mixture was heated at 90-100°C for 8-10 hours with stirring. After completion of the reaction, the mixture was cooled, water (380 mL) was added and the organic layer was separated. The organic layer was washed with a mixture of concentrated HCl and water (1:1, 2 x 350 mL) and neutralized with 20% NaOH solution (750 mL). The aqueous layer was again extracted with toluene (2 × 300 mL), and the organic layer was dried with anhydrous sodium sulfate and concentrated in vacuum to give pure 1-(bis(p-fluorophenyl)methyl)piperazine as a white to off-white solid in 88% yield.

References

[1] Journal of Medicinal Chemistry, 1997, vol. 40, # 13, p. 2047 - 2052
[2] Synthesis, 2010, # 12, p. 1989 - 1991
[3] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 4, p. 1822 - 1826
[4] Journal of Enzyme Inhibition and Medicinal Chemistry, 2014, vol. 29, # 2, p. 205 - 214
[5] Synthetic Communications, 2014, vol. 44, # 5, p. 600 - 609

4,4'-Difluorobenzhydrylpiperazine(27469-60-9)Related Product Information

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