74853-08-0

Basic information

• Product Name: 1-(4-Aminophenyl)-4-(4-hydroxyphenyl)piperazine
• Synonyms: 4-(4-(4-AMINOPHENYL)-1-PIPERZINYL)PHENOL;1-(4-AMINOPHENYL)-4-(4-HYDROXYPHENYL)PIPERAZINE;4-HYDROXYPHENYLAMINOPHENYLPIPERAZINE;4-[4-(4-aMinophenyl)piperazin-1-yl]phenol;Phenol, 4-[4-(4-aMinophenyl)-1-piperazinyl]-;POSACONZOLE INTERMEDIATE;4-[4-(4-aMinophenyl)piperazino]phenol;1-(4-AMINOPHENYL)-4-(4-HYDROXYPHENYL) PIPERZINE
• CAS NO: 74853-08-0
• Molecular Formula: C₁₆H₁₉N₃O
• Molecular Weight: 269.34
• EINECS: 1308068-626-2
• Product Categories: Piperidines, Piperidones, Piperazines
• Mol File: 74853-08-0.mol

Chemical Properties

• Boiling Point: 532.786 °C at 760 mmHg
• Flash Point: 276.02 °C
• Appearance: /
• Density: 1.237 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.662
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 12.18±0.30(Predicted)
• CAS DataBase Reference: 1-(4-Aminophenyl)-4-(4-hydroxyphenyl)piperazine(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(4-Aminophenyl)-4-(4-hydroxyphenyl)piperazine(74853-08-0)
• EPA Substance Registry System: 1-(4-Aminophenyl)-4-(4-hydroxyphenyl)piperazine(74853-08-0)

Safety Data

• Hazardous Substances Data: 74853-08-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-Aminophenyl)-4-(4-hydroxyphenyl)piperazine is used as a potential therapeutic agent for the treatment of psychiatric disorders and neurological diseases due to its pharmacological properties and potential to interact with specific biological targets relevant to these conditions.
Used in Research and Development:
In the field of medicinal chemistry, 1-(4-Aminophenyl)-4-(4-hydroxyphenyl)piperazine serves as a valuable compound for research and development. It is utilized to explore its potential as a lead compound in the discovery of new drugs targeting various medical conditions, given its unique chemical structure and pharmacological profile.

InChI:InChI=1/C16H19N3O/c17-13-1-3-14(4-2-13)18-9-11-19(12-10-18)15-5-7-16(20)8-6-15/h1-8,20H,9-12,17H2

Synthetic route

4-[4-(4-benzyloxy-phenyl)-piperazin-1-yl]-phenylamine (184177-84-2) → 1-(4-aminophenyl)-4-(4-hydroxyphenyl)piperazine (74853-08-0)

Conditions	Yield
palladium on activated charcoal In tetrahydrofuran; water at 70℃; under 4137.18 Torr; for 40h;	94%

N-(4-Hydroxyphenyl)-N'-(4'-nitrophenyl)-piperazine (112559-81-6) → 1-(4-aminophenyl)-4-(4-hydroxyphenyl)piperazine (74853-08-0)

Conditions	Yield
With sodium hypophosphite; 5%-palladium/activated carbon In 2-methoxy-ethanol; water at 70 - 80℃; for 2 - 2.5h;	88%
With ammonium formate; palladium on activated charcoal In ethyl acetate Reduction; Heating;	82%
With hydrogen In methanol; ethyl acetate at 35 - 40℃; under 2250.23 Torr; Large scale;

4-[4-(4-methoxy-phenyl)-piperazin-1-yl]-phenylamine (74852-62-3) → 1-(4-aminophenyl)-4-(4-hydroxyphenyl)piperazine (74853-08-0)

Conditions	Yield
With Cyclohexyl iodide In N,N-dimethyl-formamide at 82 - 85℃; for 3h;	85.7%
With hydrogen bromide dealkylation; Heating;

1-(4-benzyloxy-phenyl)-4-(4-nitro-phenyl)-piperazine (454479-35-7) → 1-(4-aminophenyl)-4-(4-hydroxyphenyl)piperazine (74853-08-0)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol for 24h; Heating;	81%
Multi-step reaction with 2 steps 1: 99 percent / H2 / Pd/C / H2O; tetrahydrofuran / 20 h / 50 °C / 2585.74 Torr 2: 94 percent / Pd/C / H2O; tetrahydrofuran / 40 h / 70 °C / 4137.18 Torr View Scheme

acetic acid 4-[4-(4-amino-phenyl)-piperazin-1-yl]-phenyl ester → 1-(4-aminophenyl)-4-(4-hydroxyphenyl)piperazine (74853-08-0)

Conditions	Yield
With water Hydrolysis;

Upstream product

• 100-25-4 para-dinitrobenzene 
• 6269-89-2 1-(4-Nitrophenyl)piperazine 
• 74852-61-2 1-(4-methoxyphenyl)-4-(4-nitrophenyl)-piperazine 
• 104-94-9 4-methoxy-aniline 
• 84145-43-7 1-(para-methoxyphenyl)piperazine hydrochloride 
• 3367-54-2 N,N'-di(p-chlorophenyl)piperazine 
• 106-39-8 bromochlorobenzene 
• 123-30-8 4-amino-phenol 
• 153466-15-0 4-[4-(4-nitro-phenyl)-piperazin-1-yl]-phenylamine 
• 100-00-5 4-chlorobenzonitrile 
• 38212-30-5 4-(4-methoxyphenyl)piperazine 
• 67455-41-8 4-(piperazin-1-yl)aniline 
• 586-78-7 para-nitrophenyl bromide 
• 6793-92-6 p-benzyloxyphenylbromide 

Downstream Products

• 171228-49-2 posaconazote 
• 1350560-57-4 C₃₇H₄₄F₂N₈O₅ 
• 184378-04-9 C₃₀H₃₂F₂N₆O₂ 
• 184177-83-1 2-[(1S,2S)-1-ethyl-2-benzyloxypropyl]-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)piperazin-1-yl]phenyl]-3H-1,2,4-triazol-3-one 
• 148626-66-8 2S,4R,2'S,3'S hydroxy itraconazole 
• 184177-81-9 phenyl N-(4-(4-(4-hydroxyphenyl)-1-piperazinyl)phenyl)carbamate 
• 170985-86-1 4-(4-(4-(4-(((3R,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-1-((2S,3S)-2-(benzyloxy)pentan-3-yl)-1H-1,2,4-triazol-5(4H)-one 

Relevant articles and documents

Preparation method of 4-[4-[4-(4-hydroxyphenyl) piperazine-1-yl] phenyl] phenyl carbamate

The invention discloses a preparation method of 4-[4-[4-(4-hydroxyphenyl) piperazine-1-yl] phenyl] phenyl carbamate, which comprises the following steps: by taking 4-hydroxyaniline as a raw material, carrying out ring closing on the 4-hydroxyaniline and dichloroethylamine hydrochloride to synthesize 1-(4-hydroxyphenyl) piperazine with the purity of 95A% and the correction yield of 80%; 4-nitrochlorobenzene and the prepared 1-(4-hydroxyphenyl) piperazine are coupled to synthesize 4-(4-(4-nitrophenyl)-1-piperazinyl) phenol, the purity is 93 A%, and the correction yield is 88%; then carrying out nitro reduction to synthesize 1-(4-aminophenyl)-4-(4-hydroxyphenyl) piperazine with the purity of 98A% and the correction yield of 77%; and finally, synthesizing 4-[4-[4-(4-hydroxyphenyl) piperazine-1-yl] phenyl] phenyl carbamate with the purity of 98.7%, the content of 98.5 wt% and the correction yield of 83% by using phenyl chloroformate to protect phenolic hydroxyl groups. According to the invention, the high-purity target product 4-[4-[4-(4-hydroxyphenyl) piperazine-1-yl] phenyl] phenyl carbamate can be obtained through easily available raw materials and simple process steps.

Preparation method of posaconazole intermediate 1-(4-aminophenyl)-4-(4-hydroxylphenyl)piperazine

The invention discloses a preparation method of a posaconazole intermediate, namely 1-(4-aminophenyl)-4-(4-hydroxylphenyl)piperazine, belonging to the field of medicinal chemistry. The preparation method comprises the following steps: S1, with chlorobromobenzene and anhydrous piperazine as raw materials, generating 1,4-bis(4-chlorophenyl)piperazine under certain conditions; S2, performing single-side methylation on the product generated in the step S1 to obtain 1-(4-methoxyphenyl)-4-(4-chlorophenyl)piperazine; S3, performing ammoniation on the product in the step S2 to obtain 1-(4-methoxyphenyl)-4-(4-aminophenyl)piperazine; and S4, demethylating the product obtained in the step S3, and carrying out crystallizing and purifying to obtain the 1-(4-aminophenyl)-4-(4-hydroxylphenyl)piperazine.The raw materials used in the preparation method are very cheap; reaction conditions are relatively simple; the method is easy to implement; yield is high; and the cost of a final product can be obviously reduced.

Preparation process of posaconazole intermediate 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine

The invention relates to the technical field of chemical medicine synthesis, in particular to a preparation process of posaconazole intermediate 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine. The preparation process provided by the invention comprises the following steps of a, preparing methoxyphenyl piperazine hydrochloride; b, preparing p-hydroxyphenyl piperazine hydrobromide; c, preparing 1-(4-hydroxyphenyl)-4-(4-nitrophenyl)piperazine; d, preparing a crude product of 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine; e, purifying a product. Cheap solvents and high-activity nickel catalystsare selected and used; low-pressure hydrogenation reaction is used; the raw material cost is greatly reduced; important links such as nickel ion removal and aluminum ion removal are used for post treatment; the product quality reaches the content of 99.2 percent; the single maximum noise peak value is less than 0.1 percent; the total noise peak value is less than 1.0 percent; the home and abroadmarket competitive power of the product is greatly enhanced.

Mono N-arylation of piperazine(III): Metal-catalyzed N-arylation and its application to the novel preparations of the antifungal posaconazole and its advanced intermediate

A novel application of Pd0-catalyzed arylation to mono N-arylated piperazines, its mechanism, and its application towards the novel syntheses of the key differentially N,N′-diarylated piperazine antifungal intermediate N-(4-hydroxyphenyl)-N′-(4-aminophenyl)piperazine 5 as well as posaconazole 1 are described.

Sequential mono-N-arylation of piperazine nitrogens. Part 1: A simplified method and its application to the preparation of a key N,N'-biaryl piperazine antifungal intermediate

A simple sequential N-arylation of piperazine without the use of a protecting group, catalyst, specialized equipment or a large excess of piperazine, and its application towards the preparation of the key differentially N,N'-biarylated piperazine antifungal intermediate N-(4-hydroxyphenyl)-N'-(4-aminophenyl)piperazine, 6, is described.