52605-52-4

Basic information

• Product Name: 1-(3-Chlorophenyl)-4-(3-chloropropyl)piperazine hydrochloride
• Synonyms: CCP HCL;LABOTEST-BB LT00138222;1-(3-CHLOROPHENY)-4-(3-CHLOROPROPYL) PIPERAZINE HYDROCHLORIDE;1-(3-CHLOROPHENYL)-4-(3-CHLOROPROPYL) PIPERAZINE HCL;1-[4-(3-Chlorophenyl)piperazin-1-yl]-3-chloropropane Hydrochloride;3-[4-(3-Chlorophenyl)piperazin-1-yl]propyl Chloride Hydrochloride;Trazodone IMpurity F;Trazodone Related CoMpound F
• CAS NO: 52605-52-4
• Molecular Formula: C₁₃H₁₈Cl₂N₂*ClH
• Molecular Weight: 309.66
• EINECS: 258-038-0
• Product Categories: Piperidines, Piperidones, Piperazines;Piperazine derivates;Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Piperazines;PiperazinesHeterocyclic Building Blocks;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;C12 to C14;Building Blocks;C13;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building Blocks
• Mol File: 52605-52-4.mol
• Article Data: 4

Chemical Properties

• Melting Point: 198-203 °C(lit.)
• Boiling Point: 395.8 °C at 760 mmHg
• Flash Point: 193.2 °C
• Appearance: off-white solid
• Vapor Pressure: 1.79E-06mmHg at 25°C
• Storage Temp.: Refrigerator
• Water Solubility: 3.9g/L at 28℃
• CAS DataBase Reference: 1-(3-Chlorophenyl)-4-(3-chloropropyl)piperazine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(3-Chlorophenyl)-4-(3-chloropropyl)piperazine hydrochloride(52605-52-4)
• EPA Substance Registry System: 1-(3-Chlorophenyl)-4-(3-chloropropyl)piperazine hydrochloride(52605-52-4)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-20/21/22
• Safety Statements: 26-37/39-24/25
• WGK Germany: 3
• F: 10-21
• Hazardous Substances Data: 52605-52-4(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

1-(3-Chlorophenyl)-4-(3-chloropropyl)piperazine hydrochloride is an arylpiperazine compound which is an important intermediate in the preparation of various pharmaceuticals, such as Trazodone (T718500), used to treat depression and post-traumatic stress.

General Description

1-(3-Chlorophenyl)-4-(3-chloropropyl)piperazine monohydrochloride is present as impurity in nefazodone hydrochloride (pharmaceutical formulation). Synthesis of 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine monohydrochloride is reported.

Flammability and Explosibility

Notclassified

InChI:InChI=1/C13H18Cl2N2.ClH/c14-5-2-6-16-7-9-17(10-8-16)13-4-1-3-12(15)11-13;/h1,3-4,11H,2,5-10H2;1H

Synthetic route

1-(3-chlorophenyl)piperazine hydrochloride (13078-15-4) + 1,3-chlorobromopropane (109-70-6) → 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4)

Conditions	Yield
Stage #1: 1-(3-chlorophenyl)piperazine hydrochloride; 1.3-chlorobromopropane With tetrabutylammomium bromide; potassium carbonate In acetonitrile for 0.0111111h; Microwave irradiation; Stage #2: With hydrogenchloride In 1,4-dioxane; acetone Solvent;	88%

ice-H2 O + 1-(3-chlorophenyl)piperazine hydrochloride (13078-15-4) + 1,3-chlorobromopropane (109-70-6) → 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4)

Conditions	Yield
With sodium hydroxide In hydrogenchloride; water; acetone	55.6%

3-chloropropanaldehyde (19434-65-2) + 1-(3-chlorophenyl)piperazine hydrochloride (13078-15-4) → 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4)

Conditions	Yield
Stage #1: 3-chloropropanaldehyde; 1-(3-chlorophenyl)piperazine hydrochloride In dichloromethane for 0.25h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane Inert atmosphere;

1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) + [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (6969-71-7) → trazodone (19794-93-5)

Conditions	Yield
With sodium hydroxide In isopropyl alcohol for 26h; Reagent/catalyst; Inert atmosphere; Reflux;	92%
With tetrabutylammomium bromide; potassium carbonate In acetonitrile for 0.0222222h; Time; Microwave irradiation;	92%

1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) → 1-(3-chlorophenyl)-4-(3-hydrazinopropyl)piperazine

Conditions	Yield
With hydrazine In isopropyl alcohol	85%

5-ethyl-4-(2-phenoxyethyl)-2H-1,2,4-triazol-3(4H)-one (95885-13-5) + 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) → nefazadone (83366-66-9)

Conditions	Yield
With sodium hydroxide In isopropyl alcohol for 7h; Heating;	84%

1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) + 1,2,4-triazolo<4,3-a>pyridin-3(2H)-one sodium salt → trazodone hydrochloride (25332-39-2)

Conditions	Yield
With tetrabutylammomium bromide; sodium carbonate In isopropyl alcohol at 80 - 85℃; for 12h; Reagent/catalyst;	83%

daidzein (486-66-8) + 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) → daidzein 7-ω-(3"-chlorophenylpiperozine)-4-N-propyl ether (640275-96-3)

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 80℃; for 4h;	68.2%

1,5,6,7-tetrahydro-indol-4-one (13754-86-4) + 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) → 1-{3-[4-(3-chlorophenyl)piperazine-1-yl]propyl}-1,5,6,7-tetrahydroindol-4-one (496921-70-1)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In 1,4-dioxane; dichloromethane; dimethyl sulfoxide
With hydrogenchloride; sodium hydroxide In 1,4-dioxane; dichloromethane; dimethyl sulfoxide
Stage #1: 1,5,6,7-tetrahydro-indol-4-one With sodium hydroxide In dimethyl sulfoxide at 25℃; for 0.25h; Stage #2: 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride In dimethyl sulfoxide
With hydrogenchloride; sodium hydroxide In 1,4-dioxane; dichloromethane; dimethyl sulfoxide

5-(2Methyl-1,4-dixolan-2yl)-4-(2-phenoxyethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one + potassium carbonate (584-08-7) + 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) → 2-(3-[4-(3-Chlorophenyl)-1-piperazinyl]propyl)-5-(2-methyl-1,4-dioxolan-2-yl)-2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one

Conditions	Yield
With sodium hydroxide; Ki In acetonitrile

1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) → 2-(3-[4-(3-chlorophenyl)-1-piperazinyl]propyl)-4-(2-phenoxyethyl)-4H-1,2,4-triazole-3,5(1H,2H)-dione hydrochloride (153707-87-0)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In methanol; water; isopropyl alcohol	10.21 g (47%)

1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) + 1-(3-chlorophenyl)piperazine hydrochloride (13078-15-4) + 1,3-chlorobromopropane (109-70-6) → 4-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl-2,4-dihydro-3H-1,2,4-triazol-3-one

Conditions	Yield
With sodium hydroxide In hydrogenchloride; water; acetone

theophylline (58-55-9) + 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) → C20H25ClN6O2 (58215-79-5)

Conditions	Yield
With sodium carbonate In tetrahydrofuran for 2h; Reflux;

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) → 7-{3-[4-(3-chlorophenyl)-1-piperazinyl]propoxy}-3,4-dihydrocarbostyril (72722-66-8)

Conditions	Yield
With sodium methylate In methanol Reflux;

Cyclohexanethiol (1569-69-3) + 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) → ClH*C19H29ClN2S

Conditions	Yield
Stage #1: Cyclohexanethiol With sodium hydroxide In tetrahydrofuran for 1h; Inert atmosphere; Reflux; Stage #2: 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride In tetrahydrofuran for 4h; Reflux; Inert atmosphere;

sodium phenylselenide (23974-72-3) + 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) → 1-(3-chlorophenyl)-4-(3-phenylseleno propyl)piperazine hydrochloride

Conditions	Yield
at 20℃;

1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride (52605-52-4) + [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (6969-71-7) → trazodone hydrochloride (25332-39-2)

Conditions	Yield
Stage #1: 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride; [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one With tetrabutylammomium bromide; potassium carbonate In acetonitrile Microwave irradiation; Stage #2: With hydrogenchloride In 1,4-dioxane; acetone

Upstream product

• 13078-15-4 1-(3-chlorophenyl)piperazine hydrochloride 
• 109-70-6 1.3-chlorobromopropane 
• 19434-65-2 3-chloropropanaldehyde 

Downstream Products

• 640275-96-3 daidzein 7-ω-(3-chlorophenylpiperozine)-4-N-propyl ether 
• 19794-93-5 trazodone 
• 25332-39-2 trazodone hydrochloride 
• 83366-66-9 nefazadone 
• 72722-66-8 7-{3-[4-(3-chlorophenyl)-1-piperazinyl]propoxy}-3,4-dihydrocarbostyril 
• 58215-79-5 C₂₀H₂₅ClN₆O₂ 
• 1069106-40-6 C₃₄H₃₇ClN₆O₃ 
• 1069106-28-0 C₃₃H₃₈ClN₇O₃ 
• 1069106-46-2 C₃₂H₃₅ClN₆O₃ 
• 82752-99-6 BMY 13754 
• 153707-87-0 2-(3-[4-(3-chlorophenyl)-1-piperazinyl]propyl)-4-(2-phenoxyethyl)-4H-1,2,4-triazole-3,5(1H,2H)-dione hydrochloride 
• 496921-70-1 1-{3-[4-(3-chlorophenyl)piperazine-1-yl]propyl}-1,5,6,7-tetrahydroindol-4-one 

Relevant articles and documents

Theoretical and experimental investigations into structural, electronic, molecular and biological properties of 4-(3-chlorophenyl)-1-(3-chloropropyl) piperazin-1-ium chloride

A convenient and facile synthesis of 4-(3-chlorophenyl)-1-(3-chloropropyl)piperazin-1-ium chloride is accomplished by stirring 1-(3-Chlorophenyl)piperazine hydrochloride with 3-chloropropanal by reductive amination in ethanol. The resulting compound was characterized using spectral data analysis augmented by X-ray. Single crystal analysis depicted that the synthesized compound crystallizes in monoclinic crystal system with P 21/c point group. The structural and electronic properties of the title compound have been calculated at DFT/B3LYP/6-311G (d,p) level of theory. Theoretically obtained parameters were well compared to the experimentally obtained results, showing excellent agreement. Molecular electrostatic potential surface, frontier orbital analysis and vibrational analysis were also carried out. HOMO-LUMO energy gap was calculated which allowed the calculation of relative properties like chemical hardness, chemical inertness, chemical potential, nucleophilicity and electrophilicity index of the synthesized products. Pass prediction was carried out which revealed that the target compound can be active against Prostate specific membrane protein, bearing Pa value of 0.411. Based on Pass, molecular docking studies of compound was carried out against Prostate specific membrane protein. The title compound depicted a binding free energy of ?6.3 kcal/mol and is seen to be involved in key bonding interactions which include both alkyl and mixed pi-alkyl hydrophobic interactions: Alkyl hydrophobic interactions: (LEU 259; 4.64 ?, LEU 261; 3.79 ?), mixed Pi/alkyl hydrophobic interactions: (HIS 552; 4.96 ?, HIS 553; 4.64, 5.31 ? LEU; 3.45 ?) respectively with Prostate specific membrane protein. Target compound was screened for their cytotoxic potential with various cancer cell lines being most effective against prostate. In short, this study reveals the synthesis of a 4-(3-Chlorophenyl)-1-(3-chloropropyl)piperazin-1-ium chloride and exposes its structural, electronic and biological properties, paving way for further research in the field of drug development.

Methods for the manufacture of neofazodone

Process for the manufacture of triazolone compounds and in particular nefazodone and intermediates useful in the manufacture thereof.