43156-47-4

Basic information

• Product Name: 2-Nitro-5-(phenylthio)aniline
• Synonyms: 4-phenylthio-2-aminonitrobenzene;2-NITRO-5-THIOPHENYL-ANILINE;3-Amino-5-nitrodiphenyl sulfide;2-Nitro-5-(phenylthio)aniline;2-Nitro-5-(phenylthio)benzenamine;[2-nitro-5-(phenylthio)phenyl]amine;2-nitro-5-phenylsulfanylaniline;2-nitro-5-phenylsulfanyl-aniline
• CAS NO: 43156-47-4
• Molecular Formula: C₁₂H₁₀N₂O₂S
• Molecular Weight: 246.29
• EINECS: 256-121-6
• Product Categories: API intermediates
• Mol File: 43156-47-4.mol
• Article Data: 13

Chemical Properties

• Melting Point: 145-146 °C
• Boiling Point: 472.503 °C at 760 mmHg
• Flash Point: 239.562 °C
• Appearance: /
• Density: 1.37 g/cm³
• Vapor Pressure: 4.26E-09mmHg at 25°C
• Refractive Index: 1.696
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: DMSO, Methanol
• PKA: -0.98±0.25(Predicted)
• CAS DataBase Reference: 2-Nitro-5-(phenylthio)aniline(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Nitro-5-(phenylthio)aniline(43156-47-4)
• EPA Substance Registry System: 2-Nitro-5-(phenylthio)aniline(43156-47-4)

Safety Data

• Hazardous Substances Data: 43156-47-4(Hazardous Substances Data)

Usage

Uses

2-Nitro-5-phenylthioaniline is a useful synthetic intermediate. It was used to synthesize methyl 5(6)-phenylsulfinyl-2-benzimidazolecarbamate as a potent anthelmintic.

InChI:InChI=1/C12H10N2O2S/c13-11-8-10(6-7-12(11)14(15)16)17-9-4-2-1-3-5-9/h1-8H,13H2

Synthetic route

5-chloro-2-nitroaniline (1635-61-6) + thiophenol (108-98-5) → 2-nitro-5-phenylthioaniline (43156-47-4)

Conditions	Yield
With ammonia In isopropyl alcohol	96.4%
With ammonia In 2-methyl-propan-1-ol	95.8%
With potassium hydroxide In ethanol for 4h; Heating;	83%

2-amino-4-mercapto-1-nitrobenzene + chlorobenzene (108-90-7) → 2-nitro-5-phenylthioaniline (43156-47-4)

Conditions	Yield
With potassium carbonate at 130 - 135℃; Temperature; Inert atmosphere;	95.4%

bromobenzene (108-86-1) + 2-amino-4-mercapto-1-nitrobenzene → 2-nitro-5-phenylthioaniline (43156-47-4)

Conditions	Yield
With potassium carbonate at 150 - 160℃; Temperature; Inert atmosphere;	94.3%

2-chloro-4-phenylthio nitrobenzene → 2-nitro-5-phenylthioaniline (43156-47-4)

Conditions	Yield
With ammonia In methanol at 180 - 200℃; under 13501.4 - 26252.6 Torr; for 10h; Pressure; Solvent; Temperature; Autoclave;	93.1%

2,4-dichloronitrobenzene (611-06-3) + thiophenol (108-98-5) → 2-nitro-5-phenylthioaniline (43156-47-4)

Conditions	Yield
With ammonia In isopropyl alcohol	89.5%

4-methylsulfanyl-thiophenol (1122-97-0) → 2-Bromo-4-(4-methylsulphanylphenylsulphanyl)nitrobenzene (252019-48-0) + 2-nitro-5-phenylthioaniline (43156-47-4)

5-chloro-2-nitroaniline (1635-61-6) + 1,2-diamino-4-phenylthiobenzene (43156-48-5) + 1-(methyl)-thiourea (598-52-7) + thiophenol (108-98-5) + methyl chloroformate (79-22-1) → 5-phenylmercapto-benzimidazole-2-methyl-carbaminate + 2-nitro-5-phenylthioaniline (43156-47-4)

Conditions	Yield
With sodium hydroxide In N-methyl-acetamide; water; potassium carbonate; acetic acid

1,3-Dichlorobenzene (541-73-1) → 2-nitro-5-phenylthioaniline (43156-47-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: nitric acid; sulfuric acid / 3 h / 10 - 15 °C 2: potassium hydroxide / 5,5-dimethyl-1,3-cyclohexadiene / 4 h / Reflux 3: ammonia / methanol / 10 h / 180 - 200 °C / 13501.4 - 26252.6 Torr / Autoclave View Scheme

2,4-dichloronitrobenzene (611-06-3) → 2-nitro-5-phenylthioaniline (43156-47-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide / 5,5-dimethyl-1,3-cyclohexadiene / 4 h / Reflux 2: ammonia / methanol / 10 h / 180 - 200 °C / 13501.4 - 26252.6 Torr / Autoclave View Scheme

3-chloro-aniline (108-42-9) → 2-nitro-5-phenylthioaniline (43156-47-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: nitric acid / acetic acid; sulfuric acid / 10.5 h / 20 - 25 °C 2: sodium hydroxide / methanol / 10.25 h / 90 - 95 °C View Scheme

thiophenol (108-98-5) + 4-Chloro-2-nitroaniline (89-63-4) → 2-nitro-5-phenylthioaniline (43156-47-4)

Conditions	Yield
With sodium hydroxide In methanol at 90 - 95℃; for 10.25h; Temperature;

methyl methoxyacetate (6290-49-9) + 2-nitro-5-phenylthioaniline (43156-47-4) → 2-methoxy-N-(2-nitro-5-(phenylsulfanyl)phenyl)acetamide (63470-85-9)

Conditions	Yield
at 120 - 130℃; Temperature;	95.5%

2-nitro-5-phenylthioaniline (43156-47-4) + 2-methoxyacetic acid (625-45-6) → 2-methoxy-N-(2-nitro-5-(phenylsulfanyl)phenyl)acetamide (63470-85-9)

Conditions	Yield
With pyridine; thionyl chloride In toluene at 75 - 110℃; for 10.5h; Reagent/catalyst; Solvent; Temperature;	94.8%

Methoxyacetyl chloride (38870-89-2) + 2-nitro-5-phenylthioaniline (43156-47-4) → N-(2-Amino-5-benzenesulfinyl-phenyl)-2-methoxy-acetamide (59011-22-2)

Conditions	Yield
(i) Py, benzene, (ii) H2O2, Ac2O, (iii) H2, Raney-Ni, THF; Multistep reaction;

ethoxyacetyl chloride (14077-58-8) + 2-nitro-5-phenylthioaniline (43156-47-4) → N-(2-Amino-5-phenylsulfanyl-phenyl)-2-ethoxy-acetamide (59011-18-6)

Conditions	Yield
(i) Py, benzene, (ii) H2, Raney-Ni, THF; Multistep reaction;

ethoxyacetyl chloride (14077-58-8) + 2-nitro-5-phenylthioaniline (43156-47-4) → N-(2-Amino-5-benzenesulfinyl-phenyl)-2-ethoxy-acetamide (59011-24-4)

Conditions	Yield
(i) Py, benzene, (ii) H2O2, Ac2O, (iii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + propionyl chloride (79-03-8) → 2-propionamido-4-phenylthioaniline (58306-64-2)

Conditions	Yield
(i) Py, benzene, (ii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + propionyl chloride (79-03-8) → 2-propionamido-4-phenylsulfinylaniline (58306-70-0)

Conditions	Yield
(i) Py, benzene, (ii) H2O2, Ac2O, (iii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + chloroformic acid ethyl ester (541-41-3) → (2-Amino-5-phenylsulfanyl-phenyl)-carbamic acid ethyl ester (58306-65-3)

Conditions	Yield
(i) Py, benzene, (ii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + chloroformic acid ethyl ester (541-41-3) → (2-Amino-5-benzenesulfinyl-phenyl)-carbamic acid ethyl ester (59011-21-1)

Conditions	Yield
(i) Py, benzene, (ii) H2O2, Ac2O, (iii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + n-valeryl chloride (638-29-9) → 2-Amino-5-phenylthio-valeranilid (59011-19-7)

Conditions	Yield
(i) Py, benzene, (ii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + n-valeryl chloride (638-29-9) → Pentanoic acid (2-amino-5-benzenesulfinyl-phenyl)-amide (59011-25-5)

Conditions	Yield
(i) Py, benzene, (ii) H2O2, Ac2O, (iii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + Hexanoyl chloride (142-61-0) → Hexanoic acid (2-amino-5-phenylsulfanyl-phenyl)-amide (58306-66-4)

Conditions	Yield
(i) Py, benzene, (ii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + Hexanoyl chloride (142-61-0) → Hexanoic acid (2-amino-5-benzenesulfinyl-phenyl)-amide (59011-26-6)

Conditions	Yield
(i) Py, benzene, (ii) H2O2, Ac2O, (iii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + acetyl chloride (75-36-5) → 2-Amino-5-phenylthioacetanilid (58306-63-1)

Conditions	Yield
(i) Py, benzene, (ii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + acetyl chloride (75-36-5) → 2-acetamido-1-amino-4-phenylsulfinylbenzene (54394-15-9)

Conditions	Yield
(i) Py, benzene, (ii) H2O2, Ac2O, (iii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + butyryl chloride (141-75-3) → 2-Amino-5-phenylthio-butyranilid (58306-62-0)

Conditions	Yield
(i) Py, benzene, (ii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + butyryl chloride (141-75-3) → 2-butyramido-4-phenylsulfinylaniline (59011-17-5)

Conditions	Yield
(i) Py, benzene, (ii) H2O2, Ac2O, (iii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + Phenoxyacetyl chloride (701-99-5) → N-(2-Amino-5-phenylsulfanyl-phenyl)-2-phenoxy-acetamide (58306-68-6)

Conditions	Yield
(i) Py, benzene, (ii) H2, Raney-Ni, THF; Multistep reaction;

2-nitro-5-phenylthioaniline (43156-47-4) + Phenoxyacetyl chloride (701-99-5) → N-(2-Amino-5-benzenesulfinyl-phenyl)-2-phenoxy-acetamide (59011-23-3)

Conditions	Yield
(i) Py, benzene, (ii) H2O2, Ac2O, (iii) H2, Raney-Ni, THF; Multistep reaction;

methoxycarbonylisothiocyanate (35266-49-0) + 2-nitro-5-phenylthioaniline (43156-47-4) + methyl iodide (74-88-4) → C16H17N3O2S2 (65671-13-8)

Conditions	Yield
Multistep reaction;

methoxycarbonylisothiocyanate (35266-49-0) + 2-nitro-5-phenylthioaniline (43156-47-4) → 2-nitro-5-phenylthiophenylallophanic acid methyl ester (56069-34-2)

Conditions	Yield
In acetonitrile for 15h; Heating;	3.5 g
In acetonitrile
In acetonitrile

2-nitro-5-phenylthioaniline (43156-47-4) → 1,2-diamino-4-phenylthiobenzene (43156-48-5)

Conditions	Yield
With hydrogen; nickel In ethanol under 2660 Torr; for 12h;
With hydrogen; palladium on activated charcoal In ethanol at 20℃; under 3102.89 Torr;
With platinum on activated charcoal; hydrogen In ethanol at 70 - 90℃; under 7500.75 - 15001.5 Torr; for 8h; Solvent; Reagent/catalyst;	21.2 g
With iron(III) chloride; hydrazine hydrate; pyrographite In methanol at 45 - 50℃; under 3750.38 - 7500.75 Torr; for 0.75h; Temperature; Pressure;

2-nitro-5-phenylthioaniline (43156-47-4) → Fenbendazole (43210-67-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: H2 / Pd/C / ethanol / 20 °C / 3102.89 Torr 2.1: NaOH / H2O / 0.67 h / 3 - 6 °C 2.2: 88 percent / AcOH / H2O; ethanol / 24 h / 95 °C View Scheme

2-nitro-5-phenylthioaniline (43156-47-4) → 5-Phenylthiobenzimidazole-2-thione (68828-79-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2 / Raney-nickel / ethanol / 12 h / 2660 Torr 2: KOH / ethanol / 4 h / Heating View Scheme

Upstream product

• 1122-97-0 4-methylsulfanyl-thiophenol 
• 1635-61-6 5-chloro-2-nitroaniline 
• 930-69-8 sodium thiophenolate 
• 108-90-7 chlorobenzene 
• 108-86-1 bromobenzene 
• 611-06-3 2,4-dichloronitrobenzene 
• 541-73-1 1,3-Dichlorobenzene 
• 43156-48-5 1,2-diamino-4-phenylthiobenzene 
• 598-52-7 1-(methyl)-thiourea 
• 108-98-5 thiophenol 
• 79-22-1 methyl chloroformate 
• 89-63-4 4-Chloro-2-nitroaniline 
• 108-42-9 3-chloro-aniline 

Downstream Products

• 65671-13-8 C₁₆H₁₇N₃O₂S₂ 
• 56069-34-2 2-nitro-5-phenylthiophenylallophanic acid methyl ester 
• 54394-05-7 1,2-bis-(3-carbomethoxy-2-thioureido)-4-phenylthiobenzene 
• 58306-67-5 2-amino-5-phenylthio-(2-methoxy)acetanilide 
• 63470-85-9 2-methoxy-N-(2-nitro-5-(phenylsulfanyl)phenyl)acetamide 
• 404869-97-2 2-methyl-5-phenylthiobenzimidazole 
• 60854-64-0 3-(2-benzyloxycarbonylaminoacetamido)-4-nitrodiphenyl thioether 
• 60853-78-3 3-(2-chloroacetamido)-4-nitrodiphenyl thioether 
• 60854-42-4 3-(3-chloropropionamido)-4-nitrodiphenyl thioether 
• 54029-08-2 2-acetamido-4-phenylthio-1-nitrobenzene 
• 43156-48-5 1,2-diamino-4-phenylthiobenzene 
• 59011-13-1 C₂₀H₂₃N₃O₄S₂ 
• 59011-14-2 C₁₉H₂₁N₃O₄S₂ 
• 65671-19-4 C₁₆H₁₇N₃O₃S₂ 

Relevant articles and documents

Synthetic method of fenbendazole

A synthetic method of fenbendazole belongs to the technical field of insect repellents, and specifically comprises the following steps: carrying out condensation reaction on 5-chloro-2-nitroaniline and a sodium thiophenol aqueous solution in a mixed solution of n-propyl alcohol and water to obtain 5-thiophenyl-2-nitroaniline; carrying out reduction reaction on the 5-thiophenyl-2-nitroaniline in a high-pressure kettle under the catalysis of raney nickel to generate 4-thiophenyl o-phenylenediamine; and mixing the 4-thiophenyl o-phenylenediamine and N-(trichloromethyl) methyl carbamate for a cyclization reaction to obtain fenbendazole; the method has the advantages that conditions are mild, operation is easy and convenient, ammonium chloride can be prevented from being generated in the cyclization process, and the three-waste cost is low; the generation of amine salt is avoided, and the treatment cost of three wastes is greatly reduced; and the yield of the fenbendazole can reach 84.27% to 89.99%, and the purity of the fenbendazole can reach 96.39% to 99.71%.

Preparation method of 2-amino-5-phenylthio-(2-methoxy)acetanilide

The invention belongs to the technical field of organic synthesis and particularly relates to a preparation method of 2-amino-5-phenylthio-(2-methoxy)acetanilide. According to the method, 2-nitro-5-(phenylthio)aniline is prepared from 2-nitro-5-mercaptoaniline and benzene halide and then subjected to a reaction with methyl methoxyacetate, 2-nitro-5-phenylthio-(2-methoxy)acetanilide is generated and subjected to catalytic hydrogenation reduction finally, and the target product is obtained. The preparation method has good reaction selectivity, and the obtained target product is high in purity and yield; use of high-toxicity materials is avoided, requirements for equipment and operation conditions are reduced, and safety and stability of the preparation method are improved; doses of the reaction materials are optimized, and excess benzene halide and methyl methoxyacetate can be recycled after being recovered simply; little solid waste is produced, waste treatment cost is reduced greatly,and the requirement for environmental protection is met.

Efficient Synthesis in Three Steps and Spectral Determination of Methyl-5-[(o-, m-, and p-substituted-phenylthio]-2-Benzimidazolecarbamates

The preparation and spectral properties of ten novel methyl 5-[(o-, m-, and p-substituted)-phenylthio]-2-benzimidazolecarbamates with possible pharmacological activity as antihelmintics is described; by condensation and cyclization between 5-methylthioures sulfate chloroformic acid methyl ester and 3,4-diaminophenyl-substituted-phenylthio ether dissolved in ethanol. The structures of all final products were corroborated by ir; 1H-nmr, 13C-nmr and ms.