41202-77-1

Basic information

• Product Name: 1-(2,3-Dichlorophenyl)-piperazine hydrochloride
• Synonyms: TIMTEC-BB SBB003054;N-(2,3-DICHLOROPHENYL) PIPERAZINE HCL;N-(2,3-DICHLOROPHENYL)PIPERAZINE HYDROCHLORIDE;N-(2,3-DICHLOROPHENYL)PIPERAZINE MONOHYDROCHLORIDE;PIPERAZINE, 1-(2,3-DICHLOROPHENYL)-,HYDROCHLORIDE;1-(2,3-DICHLOROPHENYL)PIPERAZINE HCL;1-[2,3-Dichlorophenyl]-PiperazineMonohydrochloride98%Min;1-(2,3-Dichlorophenyl)piperazine 98%
• CAS NO: 41202-77-1
• Molecular Formula: C₁₀H₁₂Cl₂N₂
• Molecular Weight: 267.58
• EINECS: 1533716-785-6
• Product Categories: pharmacetical;PiperazineDerivative;Piperazine derivates;API intermediates;Aromatics Compounds;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Aripiprazole;piperazines
• Mol File: 41202-77-1.mol
• Article Data: 11

Chemical Properties

• Melting Point: 242-244°C
• Boiling Point: 127°C/0.8mm
• Flash Point: 174.6 °C
• Appearance: /
• Density: 1.272 g/cm³
• Vapor Pressure: 1.77E-07mmHg at 25°C
• PKA: 8.71±0.10(Predicted)
• CAS DataBase Reference: 1-(2,3-Dichlorophenyl)-piperazine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(2,3-Dichlorophenyl)-piperazine hydrochloride(41202-77-1)
• EPA Substance Registry System: 1-(2,3-Dichlorophenyl)-piperazine hydrochloride(41202-77-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• Hazardous Substances Data: 41202-77-1(Hazardous Substances Data)

Usage

Chemical Properties

Brown Oil

InChI:InChI=1/C10H12Cl2N2.2ClH/c11-8-2-1-3-9(10(8)12)14-6-4-13-5-7-14;;/h1-3,13H,4-7H2;2*1H

Synthetic route

2,3-dichloroaniline (608-27-5) + N,N-bis(chloro-2-ethyl)amine (334-22-5) → 1-(2,3-dichlorophenyl)piperazine (41202-77-1)

Conditions	Yield
Stage #1: 2,3-dichloroaniline; N,N-bis(chloro-2-ethyl)amine With tetrabutylammomium bromide; toluene-4-sulfonic acid In 5,5-dimethyl-1,3-cyclohexadiene for 48h; Stage #2: With ammonium hydroxide pH=6 - 7;	88%

piperazine (110-85-0) + 1-bromo-2,3-dichlorobenzene (56961-77-4) → 1-(2,3-dichlorophenyl)piperazine (41202-77-1) + 1,1'-(2-chloro-1,3-phenylene)bispiperazine

Conditions	Yield
With tris(dibenzylideneacetone)dipalladium (0); (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; sodium t-butanolate In toluene for 18h; Heating;	A 62% B 7%

piperazine (110-85-0) + 1,2,3-trichlorobenzene (87-61-6) → 1-(2,3-dichlorophenyl)piperazine (41202-77-1)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl; sodium t-butanolate In 1,4-dioxane at 100℃; for 0.166667h;	37%

2,3-dichloroaniline (608-27-5) + 2,2'-iminobis[ethanol] (111-42-2) → 1-(2,3-dichlorophenyl)piperazine (41202-77-1)

Conditions	Yield
With phosphorus pentoxide; triethylamine hydrochloride at 220℃; for 4h;	31%
With phosphorus pentaoxide; triethylamine hydrochloride at 200℃; for 3h;	21%
Stage #1: 2,3-dichloroaniline; 2,2'-iminobis[ethanol] With phosphorus pentoxide; triethylamine hydrochloride at 220℃; for 4h; Inert atmosphere; Stage #2: With sodium hydroxide In water at 0℃; pH=10;	15%

piperazine (110-85-0) + 1-bromo-2,3-dichlorobenzene (56961-77-4) → 1-(2,3-dichlorophenyl)piperazine (41202-77-1)

Conditions	Yield
With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; 1,8-diazabicyclo[5.4.0]undec-7-ene; sodium t-butanolate; tris(dibenzylideneacetone)dipalladium (0) In toluene at 60 - 70℃; Buchwald amination;

1-(2,3-dichlorophenyl)-piperazine hydrochloride → 1-(2,3-dichlorophenyl)piperazine (41202-77-1)

Conditions	Yield
With sodium hydroxide In dichloromethane; water for 0.5h;

C21H32BClN2O4 → 1-(2,3-dichlorophenyl)piperazine (41202-77-1)

Conditions	Yield
With copper dichloride In methanol; water at 80℃;

bis-(2-chloroethyl)amine hydrochloride (821-48-7) + 2,3-dichloroaniline (608-27-5) → 1-(2,3-dichlorophenyl)piperazine (41202-77-1)

Conditions	Yield
With potassium iodide at 150℃; Inert atmosphere;

5-hexynyl p-toluenesulfonate (76911-01-8) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 1-(2,3-dichlorophenyl)-4-(hex-5-yn-1-yl)piperazine

Conditions	Yield
With potassium carbonate; sodium iodide In acetone for 12h; Reflux;	98%

1-(2,3-dichlorophenyl)piperazine (41202-77-1) + 2-(6-bromohexyl)–2H-naphtho[1,8-cd]isothiazole1,1-dioxide (194719-57-8) → 2-{6-[4-(2,3-dichlorophenyl)piperazin-1-yl]hexyl}-(2H)naphtho[1,8-cd][1,2]thiazole-1,1(2H)-dione hydrochloride

Conditions	Yield
Stage #1: 1-(2,3-dichlorophenyl)piperazine; 2-(6-bromohexyl)–2H-naphtho[1,8-cd]isothiazole1,1-dioxide With tetrabutylammomium bromide; potassium carbonate; sodium hydroxide In acetonitrile for 0.0138889h; Microwave irradiation; Stage #2: With hydrogenchloride In 1,4-dioxane; acetone	98%

1-(2,3-dichlorophenyl)piperazine (41202-77-1) + 8-(2-Bromoethyl)-8-azaspiro<4,5>decane-7,9-dione (150758-78-4) → 8-{2-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-ethyl}-8-aza-spiro[4.5]decane-7,9-dione

Conditions	Yield
With triethylamine at 160 - 180℃; for 0.5h;	97%

toluenesulfonic acid 3-azidobutyl ester (389131-94-6) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 1-(4-azidobutyl)-4-(2,3-dichlorophenyl)piperazine

Conditions	Yield
With potassium carbonate; sodium iodide In acetone for 12h; Reflux;	97%

3-(trans-4-(2-iodoethyl)cyclohexyl)-1,1-dimethylurea + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → Cariprazine (839712-12-8)

Conditions	Yield
With sodium carbonate In acetonitrile for 18h; Reflux; Green chemistry;	96.8%

2-(trans-4-(3,3-dimethylureido)cyclohexyl)ethyl methanesulfonate + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → Cariprazine (839712-12-8)

Conditions	Yield
With sodium carbonate In acetonitrile for 17h; Reflux; Green chemistry;	96.2%

5-(ethoxymethylene)thiazolidine-2,4-dione + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → (Z)-5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methylene)thiazolidine-2,4-dione

Conditions	Yield
Stage #1: 5-(ethoxymethylene)thiazolidine-2,4-dione; 1-(2,3-dichlorophenyl)piperazine With triethylamine In acetonitrile Stage #2: at 45℃;	96%

N-(2-formyl-trans-cyclopropylmethyl)quinoline-4-carboxamide + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → N-(2-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-trans-cyclopropylmethyl)quinoline-4-carboxamide

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 20℃; for 6h; Inert atmosphere;	96%

3-(trans-4-(2-fluoroethyl)cyclohexyl)-1,1-dimethylurea + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → Cariprazine (839712-12-8)

Conditions	Yield
With sodium carbonate In acetonitrile for 20h; Reflux; Green chemistry;	95.4%

1-(2,3-dichlorophenyl)piperazine (41202-77-1) + 4-bromobutanenitrile (5332-06-9) → 4‐[4‐(2,3‐dichlorophenyl)piperazin‐1‐yl]butannitrile (486393-38-8)

Conditions	Yield
With potassium carbonate; potassium iodide In acetone for 16h; Reflux;	95%
With triethylamine In dichloromethane for 48h;	70%
With triethylamine In dichloromethane

(2-bromoethyl)oxirane (13287-42-8) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 1-(2,3-dichlorophenyl)-4-(2-(oxiran-2-yl)ethyl)piperazine (944344-39-2)

Conditions	Yield
With potassium carbonate In acetone for 24h; Heating;	95%
With potassium carbonate In acetone for 24h; Heating / reflux;	95%
With potassium carbonate In acetone for 24h; Reflux;

1-bromo-butane (109-65-9) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 1-butyl-4-(2,3-dichlorophenyl)piperazine (1383430-54-3)

Conditions	Yield
With potassium carbonate In acetone Reflux;	95%

1,1-dimethyl-3-((trans)-4-(2-oxoethyl)cyclohexyl)urea + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → Cariprazine (839712-12-8)

Conditions	Yield
With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 20℃; for 18h; Green chemistry;	95%

bis(trichloromethyl) carbonate (32315-10-9) + 4-nitro-aniline (100-01-6) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 4-(2,3-dichlorophenyl)-N-(4-nitrophenyl)piperazine-1-carboxamide

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate; 4-nitro-aniline With triethylamine In dichloromethane at 0℃; for 0.166667h; Stage #2: 1-(2,3-dichlorophenyl)piperazine In dichloromethane at 20℃; for 1h;	95%

tridecanoic acid (638-53-9) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 1-(4-(2,3-dichlorophenyl)piperazin-1-yl)tridecan-1-one

Conditions	Yield
Stage #1: tridecanoic acid With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1-(2,3-dichlorophenyl)piperazine In N,N-dimethyl-formamide at 20℃;	95%

4-methoxybenzoic acid (100-09-4) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → (4-(2,3-dichlorophenyl)piperazin-1-yl)(4-methoxyphenyl)methanone

Conditions	Yield
Stage #1: 4-methoxybenzoic acid With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1-(2,3-dichlorophenyl)piperazine In N,N-dimethyl-formamide at 20℃;	95%

2-methyl-4-nitrobenzoic acid (1975-51-5) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → (4-(2,3-dichlorophenyl)piperazin-1-yl)(2-methyl-4-nitrophenyl)methanone

Conditions	Yield
Stage #1: 2-methyl-4-nitrobenzoic acid With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1-(2,3-dichlorophenyl)piperazine In N,N-dimethyl-formamide at 20℃;	95%

2,4 dichlorobenzoic acid (50-84-0) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → (2,4-dichlorophenyl)(4-(2,3-dichlorophenyl)piperazin-1-yl)methanone

Conditions	Yield
Stage #1: 2,4 dichlorobenzoic acid With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1-(2,3-dichlorophenyl)piperazine In N,N-dimethyl-formamide at 20℃;	95%

2-(4-methylenecyclohexyl)ethyl 4-methylbenzenesulfonate + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 1-(2,3-dichlorophenyl)-4-(2-(4-methylenecyclohexyl)ethyl)piperazine

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; Inert atmosphere;	95%

7-(4-chlorobutoxy)-3,4-dihydroquinoline-2(1H)-one (120004-79-7) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → aripiprazole (129722-12-9)

Conditions	Yield
Stage #1: 7-(4-chlorobutoxy)-3,4-dihydroquinolin-2(1H)-one With sodium iodide In N,N-dimethyl-formamide at 70 - 80℃; for 1h; Stage #2: 1-(2,3-dichlorophenyl)piperazine With potassium carbonate In N,N-dimethyl-formamide at 70 - 80℃; for 4h;	94%
With potassium carbonate In N,N-dimethyl-formamide at 100℃;	57 mg

1-chloroacetophenone (532-27-4) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 2-(4-(2,3-dichlorophenyl)piperazin-1-yl)-1-phenylethanone (1184171-35-4)

Conditions	Yield
With sodium carbonate In ethanol for 4h; Reflux;	94%

3-(trans-4-(2-chloroethyl)cyclohexyl)-1,1-dimethylurea + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → Cariprazine (839712-12-8)

Conditions	Yield
With sodium carbonate In acetone for 18h; Reflux; Green chemistry;	92.6%

2-(trans-4-(3,3-dimethylureido)cyclohexyl)ethyl 4-methylbenzenesulfonate + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → Cariprazine (839712-12-8)

Conditions	Yield
With potassium carbonate In acetonitrile for 22h; Reflux; Green chemistry;	92.5%

2-(4-bromobutyl)isoindoline-1,3-dione (5394-18-3) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 2-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl}-1H-isoindole-1,3(2H)-dione (367275-36-3)

Conditions	Yield
In xylene at 70 - 125℃; for 24h;	92%
In xylene at 70 - 125℃; for 24h;	92%
With potassium carbonate In acetone Reflux;	83%

propyl bromide (106-94-5) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 1-(2,3-dichlorophenyl)-4-propylpiperazine (871351-88-1)

Conditions	Yield
With potassium carbonate In acetone Reflux;	92%

formamide (77287-34-4, 77287-35-5, 60100-09-6) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 4-(2,3-dichlorophenyl)piperazine-1-carbaldehyde (1418125-57-1)

Conditions	Yield
With sodium methylate In tetrahydrofuran; methanol at 20℃; for 6h;	92%

1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbaldehyde + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 3-(5-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine (1507401-67-3)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 20℃; Inert atmosphere;	92%

bis(trichloromethyl) carbonate (32315-10-9) + 3-trifluoromethylaniline (98-16-8) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 4-(2,3-dichlorophenyl)-N-(3-(trifluoromethyl)phenyl)piperazine-1-carboxamide

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate; 3-trifluoromethylaniline With triethylamine In dichloromethane at 0℃; for 0.166667h; Stage #2: 1-(2,3-dichlorophenyl)piperazine In dichloromethane at 20℃; for 1h;	92%

3,4,5-trimethoxyphenyl acetic acid (951-82-6) + 1-(2,3-dichlorophenyl)piperazine (41202-77-1) → 1-(4-(2,3-dichlorophenyl)piperazin-1-yl)-2-(3,4,5-trimethoxyphenyl)ethenone

Conditions	Yield
Stage #1: 3,4,5-trimethoxyphenyl acetic acid With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 1-(2,3-dichlorophenyl)piperazine In N,N-dimethyl-formamide at 20℃;	92%

1-(2,3-dichlorophenyl)piperazine (41202-77-1) + trans-2-(1-(4-(N-tert-butoxycarbonyl)amino)cyclohexyl)acetaldehyde (215790-29-7) → trans N-tert-butoxycarbonyl-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]ethyl}-cyclohexylamine

Conditions	Yield
With sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 20℃; Inert atmosphere;	91%
With sodium tris(acetoxy)borohydride In dichloromethane	75%
With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 20℃;	69%
With platinum on carbon; hydrogen In methanol; toluene at 80℃; Reagent/catalyst; Temperature;

Upstream product

• 110-85-0 piperazine 
• 56961-77-4 1-bromo-2,3-dichlorobenzene 
• 608-27-5 2,3-dichloroaniline 
• 111-42-2 2,2'-iminobis[ethanol] 
• 334-22-5 N,N-bis(chloro-2-ethyl)amine 
• 87-61-6 1,2,3-trichlorobenzene 
• 821-48-7 bis-(2-chloroethyl)amine hydrochloride 
• 119532-26-2 1-(2,3-dichlorophenyl)-piperazine hydrochloride 

Downstream Products

• 129722-25-4 OPC 14857 
• 129722-12-9 aripiprazole 
• 367275-38-5 2-(5-(4-(2,3-dichlorophenyl)piperazin-1-yl)pentyl)isoindoline-1,3-dione 
• 877145-02-3 2-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)isoindoline-1,3-dione 
• 675599-75-4 2-[(E)-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]but-2-enyl]isoindoline-1,3-dione 

Relevant articles and documents

Progress in arylpiperazine synthesis by the catalytic amination reaction

Careful base and solvent optimization for catalytic amination is described. A Pd-catalyzed amination between some arylbromide and unprotected piperazine (1 equiv) was efficiently carried out with Pd/BINAP catalyst in a toluene-DBU solvent system, which is useful for the one-pot preparation of unsymmetrical piperazine through amination and in-situ N-protection. Reaction with N-BOC-piperazine was also successful in toluene-DBU or more polar NMP with Cs2CO3 as a key base. No reports have previously reported such solvent and base optimization in arylpiperazine synthesis.

Pd-Catalyzed Synthesis of Piperazine Scaffolds under Aerobic and Solvent-Free Conditions

A facile Pd-catalyzed methodology providing an efficient synthetic route to biologically relevant arylpiperazines under aerobic conditions is reported. Electron donating and sterically hindered aryl chlorides were aminated to afford yields up to 97%, with examples using piperazine as solvent, illustrating an ecofriendly, cost-effective synthesis of these privileged structures.

Modular C-H Functionalization Cascade of Aryl Iodides

We report the first example of ipso-borylation for the modular 1,2-bisfunctionalization of aryl iodides via C-H functionalization. The carbon-boron bond is used as a lynchpin to access ipso carbon-carbon, carbon-nitrogen, carbon-oxygen, and carbon-halogen (Cl, Br, I) bonds. The utility of our methodology is illustrated through quick, modular syntheses of the pharmaceuticals Abilify and Flunixin.