109806-71-5

Basic information

• Product Name: 4-[(4-CHLOROPHENYL)PHENYLMETHYL]-1-PIPERAZINEETHANOL DIHYDROCHLORIDE
• Synonyms: 2-{4-[(4-CHLORO-PHENYL)-PHENYL-METHYL]-PIPERAZIN-1-YL}-ETHANOL;2-[4-{Chlorophenyl}Phenylmethyl]-1-;2-[4-{4-Chlorophenyl} Phenylmethyl]-1-Piperazinylethanol;4-[(4-Chlorophenyl)phenylMethyl]-(4-hydroxy-1-piperidinyl)-1-butanone;1-Piperazineethanol, 4-[(4- chlorophenyl)phenylMethyl]-;Levocetirizine Impurity G
• CAS NO: 109806-71-5
• Molecular Formula: C₁₉H₂₃ClN₂O
• Molecular Weight: 403.77
• Product Categories: (intermediate of cetirizine dihydrochloride)
• Mol File: 109806-71-5.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 461.1 °C at 760 mmHg
• Flash Point: 232.7 °C
• Appearance: /
• Density: 1.191 g/cm³
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Ethyl Acetate (Slightly), Methanol (Slightly)
• PKA: 14.96±0.10(Predicted)
• Stability: Very Hygroscopic
• CAS DataBase Reference: 4-[(4-CHLOROPHENYL)PHENYLMETHYL]-1-PIPERAZINEETHANOL DIHYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-[(4-CHLOROPHENYL)PHENYLMETHYL]-1-PIPERAZINEETHANOL DIHYDROCHLORIDE(109806-71-5)
• EPA Substance Registry System: 4-[(4-CHLOROPHENYL)PHENYLMETHYL]-1-PIPERAZINEETHANOL DIHYDROCHLORIDE(109806-71-5)

Safety Data

• Hazardous Substances Data: 109806-71-5(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

Different sources of media describe the Uses of 109806-71-5 differently. You can refer to the following data:
1. 2-[4-[(4-Chlorophenyl)phenylmethyl]-1-piperazinyl]ethanol is an impurity of (R)-Cetirizine (C281106).
2. 4-(p-Chloro-α-phenylbenzyl)-1-piperazineethanol is used in the synthesis of antifungal triazole and imidazole derivatives. Impurity of an intermediate in the formation of Cetrizine.

Synthetic route

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol dihydrochloride → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
With sodium carbonate In water; toluene at 25℃; Heating / reflux;	95%
With sodium hydroxide In water; toluene at 55 - 60℃;
With water In toluene

1-(2-hydroxyethyl)piperazine (103-76-4) + 1-chloro-4-(chloro(phenyl)methyl)benzene (134-83-8) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
at 130℃;

N-(4-chlorobenzhydryl)piperazine (303-26-4) + 2-bromoethanol (540-51-2) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
With TEA In toluene Alkylation;

N-(4-chlorobenzhydryl)piperazine (303-26-4) + 2-chloro-ethanol (107-07-3) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
With triethylamine In toluene Heating / reflux;
With triethylamine at 110℃;

(4-chlorophenyl)phenylmethanol (119-56-2) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / toluene / 1 h / 85 - 90 °C / Large scale reaction 2.1: toluene / 3 h / 80 °C / Large scale reaction 2.2: pH 1 / Large scale reaction 3.1: water / toluene View Scheme

1-chloro-4-(chloro(phenyl)methyl)benzene (134-83-8) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene / 3 h / 80 °C / Large scale reaction 1.2: pH 1 / Large scale reaction 2.1: water / toluene View Scheme

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol dihydrochloride → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
With sodium carbonate In water; toluene at 25℃; Heating / reflux;	95%
With sodium hydroxide In water; toluene at 55 - 60℃;
With water In toluene

1-(2-hydroxyethyl)piperazine (103-76-4) + 1-chloro-4-(chloro(phenyl)methyl)benzene (134-83-8) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
at 130℃;

N-(4-chlorobenzhydryl)piperazine (303-26-4) + 2-bromoethanol (540-51-2) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
With TEA In toluene Alkylation;

N-(4-chlorobenzhydryl)piperazine (303-26-4) + 2-chloro-ethanol (107-07-3) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
With triethylamine In toluene Heating / reflux;
With triethylamine at 110℃;

(4-chlorophenyl)phenylmethanol (119-56-2) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / toluene / 1 h / 85 - 90 °C / Large scale reaction 2.1: toluene / 3 h / 80 °C / Large scale reaction 2.2: pH 1 / Large scale reaction 3.1: water / toluene View Scheme

1-chloro-4-(chloro(phenyl)methyl)benzene (134-83-8) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene / 3 h / 80 °C / Large scale reaction 1.2: pH 1 / Large scale reaction 2.1: water / toluene View Scheme

4-chlorobenzophenone (134-85-0) → 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; Aliquat 336 / toluene / 20 °C / Large scale reaction 1.2: 5 h / 50 °C / Large scale reaction 2.1: thionyl chloride / toluene / 1 h / 85 - 90 °C / Large scale reaction 3.1: toluene / 3 h / 80 °C / Large scale reaction 3.2: pH 1 / Large scale reaction 4.1: water / toluene View Scheme

cetirizine dihydrochloride (83881-52-1) → 2-(piperazin-1-yl)acetaldehyde (1247549-57-0) + 4-chlorophenyl(phenyl)methane (831-81-2) + 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5)

Conditions	Yield
With laccase from Aspergillus oryzae In aq. phosphate buffer at 60℃; pH=6; pH-value; Temperature; Sonication; Enzymatic reaction;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + Bromoacetaldehyde diethyl acetal (2032-35-1) → 2-{2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy}acetaldehyde diethylacetal (290362-10-6)

Conditions	Yield
Stage #1: 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol With sodium hydride In tetrahydrofuran at 50℃; for 0.333333h; Stage #2: Bromoacetaldehyde diethyl acetal In tetrahydrofuran at 50 - 90℃; for 10h; Stage #3: With water In tetrahydrofuran	96.7%

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + sodium monochloroacetic acid (3926-62-3) → cetirizine dihydrochloride (83881-52-1)

Conditions	Yield
Stage #1: 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol; sodium monochloroacetic acid With sodium hydroxide In water; dimethyl sulfoxide; toluene at 30 - 35℃; for 14 - 18h; Stage #2: With hydrogenchloride In water; acetone at 20℃;	87.4%

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) → 1-(2-chloroethyl)-4-[(4-chlorophenyl)(phenyl)methyl]piperazine (102163-64-4)

Conditions	Yield
With pyridine; thionyl chloride for 16h; Reflux;	30%
With thionyl chloride at 60℃;
With thionyl chloride for 6h; Reflux;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + CH3CH2CH(halide)-CO2H → 2-(2-{4-[(4-chloro-phenyl)-phenyl-methyl]-piperazin-1-yl}-ethoxy)-butyric acid

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol Etherification;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + (m-OCH3)-C6H4-CH2-halide → 1-[(4-chloro-phenyl)-phenyl-methyl]-4-[2-(3-methoxy-benzyloxy)-ethyl]-piperazine

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol Etherification;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + (p-OCH3)-C6H4-CH2-halide → 1-[(4-chloro-phenyl)-phenyl-methyl]-4-[2-(4-methoxy-benzyloxy)-ethyl]-piperazine

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol Etherification;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + (p-isopropyl)-C6H4-CH2-halide → 1-[(4-chloro-phenyl)-phenyl-methyl]-4-[2-(4-isopropyl-benzyloxy)-ethyl]-piperazine

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol Etherification;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + halide-CH(Ph)-CO2H → 2-(2-{4-[(4-chloro-phenyl)-phenyl-methyl]-piperazin-1-yl}-ethoxy)-3-phenyl-propionic acid

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol Etherification;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + (2-naphthyl)-CH2-halide → 1-[(4-chloro-phenyl)-phenyl-methyl]-4-[2-(naphthalen-2-ylmethoxy)-ethyl]-piperazine

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol Etherification;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + (1-naphthyl)-CH2-halide → 1-[(4-chloro-phenyl)-phenyl-methyl]-4-[2-(naphthalen-1-ylmethoxy)-ethyl]-piperazine

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol Etherification;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + halide-CH2-p-C6H4-CH2CO2H → [4-(2-{4-[(4-chloro-phenyl)-phenyl-methyl]-piperazin-1-yl}-ethoxymethyl)-phenyl]-acetic acid

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol Etherification;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) → (+)-[2-[4-[(4-chlorophenyl)-phenyl methyl]-1-piperazinyl]]ethanol (705289-61-8)

Conditions	Yield
at 25℃; Resolution of racemate;	n/a

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + sodium monochloroacetic acid (3926-62-3) → cetirizine (83881-51-0)

Conditions	Yield
Stage #1: 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol; sodium monochloroacetic acid With potassium hydroxide In DMF (N,N-dimethyl-formamide) at 153℃; for 4 - 5h; Stage #2: With hydrogenchloride In DMF (N,N-dimethyl-formamide); water pH=4.0 - 4.5;
Stage #1: 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol; sodium monochloroacetic acid With potassium hydroxide In DMF (N,N-dimethyl-formamide) at 25 - 35℃; for 10 - 12h; Stage #2: With hydrogenchloride; water at 25 - 35℃; pH=5 - 5.5;
With sodium hydroxide In dimethyl sulfoxide at 20 - 40℃; for 20h; Product distribution / selectivity;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + chloroacetic acid (79-11-8) → cetirizine (83881-51-0)

Conditions	Yield
With sodium hydroxide In water; dimethyl sulfoxide; toluene at 30 - 35℃; for 20h; Product distribution / selectivity;

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) → 1-[(4-chlorophenyl)(phenyl)methyl]-4-[2-(1H-1,2,4-triazole-1-yl)ethyl]piperazine (1275578-39-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine; thionyl chloride / 16 h / Reflux 2: tetraethylammonium iodide; potassium carbonate; sodium hydroxide / acetonitrile / 24 h / Reflux View Scheme

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) → 1-[(4-chlorophenyl)(phenyl)methyl]-4-[2-(1H-imidazol-1-yl)ethyl]piperazine (1345892-34-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine; thionyl chloride / 16 h / Reflux 2: tetraethylammonium iodide; potassium carbonate; sodium hydroxide / acetonitrile / 38 h / Reflux View Scheme

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) → cetirizine dihydrochloride (83881-52-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium methylate / toluene / 10 - 15 °C / Inert atmosphere; Large scale reaction 1.2: 2 h / 50 - 60 °C / Large scale reaction 2.1: water; sodium hydroxide / 3 h / Reflux; Large scale reaction View Scheme

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) + 2-chloro-N,N-dimethylacetamide (2675-89-0) → 2-(2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)-N,N-dimethylacetamide dihydrochloride

Conditions	Yield
Stage #1: 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol With sodium methylate In toluene at 10 - 15℃; Inert atmosphere; Large scale reaction; Stage #2: 2-chloro-N,N-dimethylacetamide at 50 - 60℃; for 2h; Large scale reaction; Stage #3: With hydrogenchloride In water

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) → 1-((4-chlorophenyl)(phenyl)methyl)-4-(2-(piperazin-1-yl)ethyl)piperazine

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / 60 °C 2: potassium carbonate / N,N-dimethyl-formamide / 80 °C 3: hydrogenchloride / methanol / 50 °C View Scheme
Multi-step reaction with 3 steps 1: thionyl chloride / 6 h / Reflux 2: potassium carbonate / 4 h / Reflux 3: hydrogenchloride / water / 2 h / 20 °C View Scheme

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) → (Z)-5-((4-(2-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)ethyl)piperazin-1-yl)methylene)thiazolidine-2,4-dione

Conditions	Yield
Multi-step reaction with 4 steps 1.1: thionyl chloride / 60 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 80 °C 3.1: hydrogenchloride / methanol / 50 °C 4.1: triethylamine / acetonitrile 4.2: 45 °C View Scheme

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) → C28H39ClN4O2

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / 60 °C 2: potassium carbonate / N,N-dimethyl-formamide / 80 °C View Scheme
Multi-step reaction with 2 steps 1: thionyl chloride / 6 h / Reflux 2: potassium carbonate / 4 h / Reflux View Scheme

2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol (109806-71-5) → C25H35ClN4O

Conditions	Yield
Multi-step reaction with 4 steps 1: thionyl chloride / 6 h / Reflux 2: potassium carbonate / 4 h / Reflux 3: hydrogenchloride / water / 2 h / 20 °C 4: triethylamine / toluene / 8 h / Reflux View Scheme

Upstream product

• 103-76-4 1-(2-hydroxyethyl)piperazine 
• 134-83-8 1-chloro-4-(chloro(phenyl)methyl)benzene 
• 303-26-4 N-(4-chlorobenzhydryl)piperazine 
• 540-51-2 2-bromoethanol 
• 1177093-13-8 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethan-1-ol dihydrochloride 
• 107-07-3 2-chloro-ethanol 
• 119-56-2 (4-chlorophenyl)phenylmethanol 
• 134-85-0 4-chlorobenzophenone 
• 83881-52-1 cetirizine dihydrochloride 

Downstream Products

• 83881-51-0 cetirizine 
• 1275578-39-6 1-[(4-chlorophenyl)(phenyl)methyl]-4-[2-(1H-1,2,4-triazole-1-yl)ethyl]piperazine 
• 1345892-34-3 1-[(4-chlorophenyl)(phenyl)methyl]-4-[2-(1H-imidazol-1-yl)ethyl]piperazine 
• 102163-64-4 1-(2-chloroethyl)-4-[(4-chlorophenyl)(phenyl)methyl]piperazine 
• 83881-52-1 cetirizine dihydrochloride 
• 290362-10-6 2-{2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy}acetaldehyde diethylacetal 
• 705289-61-8 (+)-[2-[4-[(4-chlorophenyl)-phenyl methyl]-1-piperazinyl]]ethanol 

Relevant articles and documents

New manufacturing procedure of cetirizine

A new procedure for the manufacture of cetirizine dihydrochloride via the new intermediate 2-(2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)- N,N-dimethylacetamide dihydrochloride, synthesized by O-alkylation of 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethanol with 2-chloro-N,N-dimethylacetamide, is elaborated. Hydrolysis of the resulting amide and subsequent salification provided cetirizine dihydrochloride.

Ultrasound assisted enzyme catalyzed degradation of Cetirizine dihydrochloride

Cetirizine dihydrochloride, a pharmaceutical drug of the class antihistamines is frequently detected in wastewater samples. In the present work, the degradation of Cetirizine dihydrochloride is carried out using a novel technique of laccase enzyme as a catalyst under the influence of ultrasound irradiation. Effect of various process parameters such as enzyme loading, temperature, power, duty cycle, frequency and speed of agitation has been studied along with identification of the degradation intermediates. The maximum degradation of 91% is achieved at optimized experimental parameters such as 0.02% enzyme loading (w/v), 50°C temperature, power input of 100 W, 25 kHz frequency and 50% duty cycle with agitation speed of 200 rpm. It is observed that enzymatic degradation of Cetirizine dihydrochloride under the influence of ultrasound irradiation not only enhances the degradation but also reduces the time of degradation as compared to conventional enzymatic degradation technique.

2-[2-[4-[(4-CHLOROPHENYL) PHENYLMETHYL]-1-PIPERAZINYL]ETHOXY]ACETIC ACID MONOHYDROCHLORIDE AS ANTI-ALLERGENIC COMPOUND AND PROCESS FOR ITS PRODUCTION

An anti-allergenic compound having therapeutic value and a process for its manufacture. The disclosure is directed to 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1piperazinyl]ethoxy]acetic acid monohydrochloride, to compositions containing 2-[2-[4-[(4chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid monohydrochloride, and to a process for the preparation of 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid monohydrochloride.