51-78-5

Basic information

• Product Name: 4-Hydroxyaniline hydrochloride
• Synonyms: 4-amino-phenohydrochloride;c.i.76551;C.I.OxidationBase6A(76551);ci76551;durafurbrownr;fouraminecp;fourrine83;fourrinep
• CAS NO: 51-78-5
• Molecular Formula: C₆H₇NO*ClH
• Molecular Weight: 145.59
• EINECS: 200-122-6
• Mol File: 51-78-5.mol
• Article Data: 3

Chemical Properties

• Melting Point: 302 °C
• Boiling Point: 282 °C at 760 mmHg
• Flash Point: 124.3 °C
• Appearance: gray/powder
• Density: 1.21g/cm3
• Vapor Pressure: 0.00202mmHg at 25°C
• Storage Temp.: Store below +30°C.
• Water Solubility: soluble
• Stability: Stable, but hygroscopic, air and light sensitive. Incompatible with strong oxidizing agents.
• Merck: 14,462
• BRN: 3911747
• CAS DataBase Reference: 4-Hydroxyaniline hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Hydroxyaniline hydrochloride(51-78-5)
• EPA Substance Registry System: 4-Hydroxyaniline hydrochloride(51-78-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-43
• Safety Statements: 28-36
• WGK Germany: 3
• RTECS: SJ6070000
• Hazardous Substances Data: 51-78-5(Hazardous Substances Data)

Usage

Chemical Properties

Off white powder

Uses

4-Aminophenol may be used as a pharmaceutical reference standard for the determination of the analyte in pharmaceutical formulations using surface enhanced Raman scattering method.

General Description

Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards. 4-Aminophenol hydrochloride can be used to study cell biology, bioactive small molecules, chemical synthesis, organic building blocks, oxygen compounds and phenols.

Safety Profile

Moderately toxic byintraperitoneal route. Mutation data reported. Whenheated to decomposition it emits very toxic fumes of HCland NOx.

Purification Methods

Purify the salt by treating an aqueous solution with saturated Na2S2O3, filtering under N2, then recrystallising it from 50% EtOH twice and once from absolute EtOH [Livingston & Ke J Am Chem Soc 72 909 1950]. [Beilstein 13 III 993.]

InChI:InChI=1/C6H7NO.ClH/c7-5-1-3-6(8)4-2-5;/h1-4,8H,7H2;1H

Synthetic route

4-nitro-phenol (100-02-7) → p-aminophenol hydrochloride (51-78-5)

Conditions	Yield
Stage #1: 4-nitro-phenol With sodium tetrahydroborate; water at 20℃; for 2h; Stage #2: With hydrogenchloride In ethyl acetate	93%

hydrogenchloride (7647-01-0) + 5-amino-2-hydroxybenzenesulfonic acid (2835-04-3) → p-aminophenol hydrochloride (51-78-5)

Conditions	Yield
at 170℃; im geschlossenen Rohr;

hydrogenchloride (7647-01-0) + α-methylsuccinic di-p-anisidine (78533-09-2) → methylene chloride (74-87-3) + 2-methylbutanedioic acid (498-21-5, 636-60-2) + p-aminophenol hydrochloride (51-78-5)

Conditions	Yield
at 100℃;

4-amino-phenol (123-30-8) → p-aminophenol hydrochloride (51-78-5)

Conditions	Yield
With hydrogenchloride In ethanol

phenol (108-95-2) → p-aminophenol hydrochloride (51-78-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium azide / 5 h / 55 - 60 °C 2: hydrogenchloride / ethanol View Scheme

2-chloro-4,8-dimethyl-quinoline (3913-17-5) + p-aminophenol hydrochloride (51-78-5) → 4-(4,8-dimethylquinolin-2-ylamino)phenol hydrochloride (1436858-68-2)

Conditions	Yield
With hydrogenchloride In ethanol; water Heating;	94%

p-aminophenol hydrochloride (51-78-5) + 1-(tert-butoxy)-2-(tert-butoxy)carbonyl-1,2-dihydroisoquinoline (404586-94-3) → 4-N-tert-butoxycarbonylaminophenol (54840-15-2) + tert-butyl (4-((tert-butoxycarbonyl)oxy)phenyl)carbamate (95932-40-4)

Conditions	Yield
In 1,2-dimethoxyethane at 20℃;	A 93% B n/a
In 1,2-dimethoxyethane at 20℃; for 16h;	A 93% B 5%

4-chloro-2,8-dimethylquinoline (32314-39-9) + p-aminophenol hydrochloride (51-78-5) → 4-(2,8-dimethylquinolin-4-ylamino)phenol dihydrochloride

Conditions	Yield
With hydrogenchloride In ethanol; water for 10h; Heating;	93%

2-chloro-4,6-dimethylquinoline (3913-18-6) + p-aminophenol hydrochloride (51-78-5) → 4-(4,6-dimethylquinolin-2-ylamino)phenol hydrochloride (1436858-62-6)

Conditions	Yield
With hydrogenchloride In ethanol; water Heating;	92%

p-aminophenol hydrochloride (51-78-5) + (4-formylphenoxy)acetic acid (22042-71-3) → 4-<<(4-hydoxyanilino)carbonyl>methoxy>benzaldehyde (96865-80-4)

Conditions	Yield
With TEA; dicyclohexyl-carbodiimide In tetrahydrofuran; N,N-dimethyl-formamide for 2h;	89%

4-methyl-2,6-dioxo-1-propyl-1,2,5,6-tetrahydropyridine-3-carbonitrile (1161733-88-5) + p-aminophenol hydrochloride (51-78-5) → 5-[(4-hydroxyphenyl)-hydrazono]-4-methyl-2,6-dioxo-1-propyl-1,2,5,6-tetrahydropyridine-3-carbonitrile (1397715-49-9)

Conditions	Yield
Stage #1: p-aminophenol hydrochloride With sodium nitrite In water Cooling; Stage #2: 4-methyl-2,6-dioxo-1-propyl-1,2,5,6-tetrahydropyridine-3-carbonitrile With sodium acetate In ethanol; water at 20℃; for 1h; Cooling;	88%

p-aminophenol hydrochloride (51-78-5) + 4-Nitrobenzenesulfonyl chloride (98-74-8) → N-(4-hydroxyphenyl)-4-nitrobenzenesulfonamide (50994-51-9)

Conditions	Yield
In pyridine at 20℃; for 5h; Cooling with ice;	88%

p-aminophenol hydrochloride (51-78-5) + 11-azido-3,6,9-trioxaundecanoic acid (172531-37-2) → C14H20N4O5 (1096439-18-7)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃;	87%

p-aminophenol hydrochloride (51-78-5) + p-toluenesulfonyl chloride (98-59-9) → N-(4-hydroxyphenyl)-4-methylbenzenesulfonamide (1146-43-6)

Conditions	Yield
In pyridine at 20℃; for 5h; Cooling with ice;	87%

4-chloro-8-methoxy-2-methylquinoline (64951-58-2) + p-aminophenol hydrochloride (51-78-5) → 4-(8-methoxy-2-methylquinolin-4-ylamino)phenol dihydrochloride

Conditions	Yield
With hydrogenchloride In ethanol; water for 10h; Heating;	86%

ammonium thiocyanate (1147550-11-5) + p-aminophenol hydrochloride (51-78-5) → 1-(4-hydroxyphenyl)thiourea (1520-27-0)

Conditions	Yield
Heating;	85%
Stage #1: p-aminophenol hydrochloride With hydrogenchloride In water for 0.5h; Reflux; Stage #2: ammonium thiocyanate In water at 20℃; for 4h; Reflux;

4-chloro-2,6-dimethylquinoline (6270-08-2) + p-aminophenol hydrochloride (51-78-5) → 4-(2,6-dimethylquinolin-4-ylamino)phenol dihydrochloride

Conditions	Yield
With hydrogenchloride In ethanol; water for 10h; Heating;	84%

2-chloro-4-methylquinoline (634-47-9) + p-aminophenol hydrochloride (51-78-5) → 4-(4-methylquinolin-2-ylamino)phenol hydrochloride (1225153-42-3)

Conditions	Yield
With hydrogenchloride In ethanol; water Heating;	84%

p-aminophenol hydrochloride (51-78-5) + 1-(4-chlorophenyl)-3-methyl-2-pyrazolin-5-one (13024-90-3) → 2-(4-chloro-phenyl)-4-[(4-hydroxy-phenyl)-hydrazono]-5-methyl-2,4-dihydro-pyrazol-3-one

Conditions	Yield
Stage #1: p-aminophenol hydrochloride With hydrogenchloride; sodium nitrite In water at 0 - 5℃; Stage #2: 1-(4-chlorophenyl)-3-methyl-2-pyrazolin-5-one With sodium hydroxide; aluminium trichloride In water for 0.5h; pH=8.0 - 8.5; cooling;	83%

4-chloro-6-methoxy-2-methylquinoline (50593-73-2) + p-aminophenol hydrochloride (51-78-5) → 4-(6-methoxy-2-methylquinolin-4-ylamino)phenol dihydrochloride

Conditions	Yield
With hydrogenchloride In ethanol; water for 10h; Heating;	83%

4-chloro-2-methylquinoline (4295-06-1) + p-aminophenol hydrochloride (51-78-5) → 4-(2-methylquinolin-4-ylamino)phenol dihydrochloride

Conditions	Yield
With hydrogenchloride In ethanol; water for 10h; Heating;	82%

p-aminophenol hydrochloride (51-78-5) + 5-hydroxy-3-methyl-1-(pyrid-2-yl)-1H-pyrazole (38695-92-0) → 4-[(4-hydroxy-phenyl)-hydrazono]-5-methyl-2-pyridin-2-yl-2,4-dihydro-pyrazol-3-one

Conditions	Yield
Stage #1: p-aminophenol hydrochloride With hydrogenchloride; sodium nitrite In water at 0 - 5℃; Stage #2: 5-hydroxy-3-methyl-1-(pyrid-2-yl)-1H-pyrazole With sodium hydroxide; aluminium trichloride In water for 0.5h; pH=8.0 - 8.5; cooling;	81%

p-aminophenol hydrochloride (51-78-5) + 4-methoxy-phenyl-sulphonyl chloride (98-68-0) → N-(4-hydroxyphenyl)-4-methoxybenzenesulfonamide

Conditions	Yield
In pyridine at 20℃; for 5h; Cooling with ice;	80%

p-aminophenol hydrochloride (51-78-5) + 1-(4-methoxyphenyl)-3-methyl-2-pyrazolin-5-one (60798-06-3) → 4-[(4-hydroxy-phenyl)-hydrazono]-2-(4-methoxy-phenyl)-5-methyl-2,4-dihydro-pyrazol-3-one

Conditions	Yield
Stage #1: p-aminophenol hydrochloride With hydrogenchloride; sodium nitrite In water at 0 - 5℃; Stage #2: 1-(4-methoxyphenyl)-3-methyl-2-pyrazolin-5-one With sodium hydroxide; aluminium trichloride In water for 0.5h; pH=8.0 - 8.5; cooling;	79%

2,6-dichlorobenzenesulfonyl chloride (6579-54-0) + p-aminophenol hydrochloride (51-78-5) → 2,6-dichloro-N-(4-hydroxyphenyl)benzenesulfonamide (19818-15-6)

Conditions	Yield
In pyridine at 20℃; for 5h; Cooling with ice;	79%

p-aminophenol hydrochloride (51-78-5) + 2-Naphthalenesulfonyl chloride (93-11-8) → naphthalene-2-sulfonic acid (4-hydroxyl-phenyl)-amide (51767-49-8)

Conditions	Yield
In pyridine at 20℃; for 5h; Cooling with ice;	78%

p-aminophenol hydrochloride (51-78-5) + 4-chlorobenzenesulfonyl chloride (98-60-2) → 4-chloro-N-(4-hydroxyphenyl)benzenesulfonamide (63301-13-3)

Conditions	Yield
In pyridine at 20℃; for 5h; Cooling with ice;	75%

2,4,6-triisopropylphenylsulfonyl chloride (6553-96-4) + p-aminophenol hydrochloride (51-78-5) → N-(4-hydroxyphenyl)-2,4,6-triisopropylbenzenesulfonamide (212248-51-6)

Conditions	Yield
In pyridine at 20℃; for 5h; Cooling with ice;	75%

p-aminophenol hydrochloride (51-78-5) + 4-nitro-benzoyl chloride (122-04-3) → N-(4-hydroxyphenyl)-4-nitrobenzamide (13160-56-0)

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 5h; Cooling with ice;	74%

3,5-dihydroxybenzaldehyde (26153-38-8) + p-aminophenol hydrochloride (51-78-5) → (E)-5{(4-hydroxyphenylimino)methyl}benzene-1,3-diol

Conditions	Yield
Stage #1: p-aminophenol hydrochloride With triethylamine In ethanol at 20℃; for 0.0833333h; Stage #2: 3,5-dihydroxybenzaldehyde With acetic acid In ethanol for 8h; Reflux;	73%

3,4,5-trihydroxybenzaldehyde monohydrate (207742-88-9) + p-aminophenol hydrochloride (51-78-5) → (E)-5{(4-hydroxyphenylimino)methyl}benzene-1,2,3-triol (1448846-11-4)

Conditions	Yield
Stage #1: p-aminophenol hydrochloride With triethylamine In ethanol at 20℃; for 0.0833333h; Stage #2: 3,4,5-trihydroxybenzaldehyde monohydrate With acetic acid In ethanol Reflux;	70%

p-aminophenol hydrochloride (51-78-5) + di-tert-butyl (2S,4E)-4-[(dimethylamino)methylidene]-5-oxopyrrolidine-1,2-dicarboxylate (151121-34-5) → di-tert-butyl (2S,4E)-4-[(4-hydroxyanilino)methylidene]-5-oxopyrrolidine-1,2-dicarboxylate (1252661-52-1)

Conditions	Yield
In ethanol; water at 20℃; for 24h;	69%

1-Naphthalenesulfonyl chloride (85-46-1) + p-aminophenol hydrochloride (51-78-5) → N-(4-hydroxyphenyl)naphthalene-1-sulfonamide (50994-44-0)

Conditions	Yield
In pyridine at 20℃; for 5h; Cooling with ice;	68%

p-aminophenol hydrochloride (51-78-5) + methanesulfonyl chloride (124-63-0) → 4-(methylsulfonylamino)phenol (51767-39-6)

Conditions	Yield
In pyridine at 20℃; for 5h; Cooling with ice;	68%

Upstream product

• 7647-01-0 hydrogenchloride 
• 2835-04-3 5-amino-2-hydroxybenzenesulfonic acid 
• 78533-09-2 α-methylsuccinic di-p-anisidine 
• 100-02-7 4-nitro-phenol 
• 108-95-2 phenol 
• 123-30-8 4-amino-phenol 

Downstream Products

• 28363-27-1 2-((4-hydroxyphenyl)amino)acetonitrile 
• 81099-86-7 4-[(7-chloroquinolin-4-yl)amino]phenol 
• 6907-57-9 4-(7-chloro-2-methyl-quinolin-4-ylamino)-phenol 
• 55284-25-8 4-(3-nitro-cinnamylidenamino)-phenol 
• 68142-12-1 4-(4-chloro-2,6-dinitro-anilino)-phenol 
• 1520-27-0 1-(4-hydroxyphenyl)thiourea 
• 1752-24-5 4,4'-dihydroxydiphenylamine 
• 5428-97-7 carbamoylsulfanyl-acetic acid-(4-hydroxy-anilide) 
• 75140-07-7 4-(4-hydroxy-anilino)-[1,2]naphthoquinone 
• 89-57-6 5-Aminosalicylic Acid 
• 64693-23-8 1,4-benzoquinone-N-bromoimine 
• 51828-71-8 4-hydroxy-1-[4-(hydroxyphenyl)azo]naphthalene 
• 259235-78-4 2-((p-hydroxyphenyl)amino)-2-phenylacetonitrile 
• 588-53-4 4-benzylidenamino-phenol 

Relevant articles and documents

Cobalt-Catalyzed Deoxygenative Hydroboration of Nitro Compounds and Applications to One-Pot Synthesis of Aldimines and Amides

The commercially available and bench-stable Co(acac)2 ligated with bis[(2-diphenylphosphino)phenyl] ether (dpephos) was employed for selective room temperature hydroboration of nitro compounds with HBPin (TOF up to 4615 h?1), tolerating halide, hydroxy, amino, ether, ester, lactone, amide and heteroaromatic functionalities. These reactions offered a direct access to a variety of N-borylamines RN(H)BPin, which were in situ treated with aldehydes and carboxylic acids to produce a series of aldimines and secondary carboxamides without the need for dehydrating and/or coupling reagents. Combination of these transformations in a sequential one-pot manner allowed for direct and selective synthesis of aldimines and secondary carboxamides from readily available and inexpensive nitro compounds.

New method for the direct electrophilic amination of aromatic compounds and its use in the annelation of the pyrimidine ring

A method has been developed for the synthesis of aromatic amines by the amination of the corresponding aromatic compounds using sodium azide in PPA. A method for the synthesis of quinazolines and benzo[h]quinazolines using this reaction and the subsequent reaction of the intermediates with 1,3,5-triazines has been developed.