616-86-4

Basic information

• Product Name: 4-ETHOXY-2-NITROANILINE
• Synonyms: TIMTEC-BB SBB000231;VITAS-BB TBB000165;4-ethoxy-2-nitro-benzenamin;Benzenamine, 4-ethoxy-2-nitro-;p-Phenetidine, 2-nitro-;ART-CHEM-BB B020041;AKOS B020041;4-ETHOXY-2-NITROANILINE
• CAS NO: 616-86-4
• Molecular Formula: C₈H₁₀N₂O₃
• Molecular Weight: 182.18
• EINECS: 210-497-8
• Product Categories: Intermediates of Dyes and Pigments
• Mol File: 616-86-4.mol

Chemical Properties

• Melting Point: 111-113 °C(lit.)
• Boiling Point: 346.2 °C at 760 mmHg
• Flash Point: 163.2 °C
• Appearance: /
• Density: 1.264 g/cm³
• Vapor Pressure: 5.83E-05mmHg at 25°C
• Refractive Index: 1.585
• PKA: 1.01±0.10(Predicted)
• CAS DataBase Reference: 4-ETHOXY-2-NITROANILINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-ETHOXY-2-NITROANILINE(616-86-4)
• EPA Substance Registry System: 4-ETHOXY-2-NITROANILINE(616-86-4)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 26-37/39
• WGK Germany: 3
• Hazardous Substances Data: 616-86-4(Hazardous Substances Data)

Usage

Uses

Used in Chemical Synthesis:
4-Ethoxy-2-nitroaniline is used as a chemical intermediate in the synthesis of various organic compounds and dyes. Its unique structure allows it to be a versatile building block for the development of new chemical entities with potential applications in different industries.
Used in Environmental Research:
Due to its classification as a biological environmental toxin, 4-Ethoxy-2-nitroaniline is utilized in research studies aimed at understanding the effects of environmental toxins on living organisms and ecosystems. This knowledge is crucial for developing strategies to mitigate the impact of such toxins and protect the environment and public health.

InChI:InChI=1/C8H10N2O3/c1-2-13-6-3-4-7(9)8(5-6)10(11)12/h3-5H,2,9H2,1H3

Synthetic route

N-(4-ethoxy-2-nitrophenyl)acetamide (885-81-4) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
With methanol; sodium hydride In tetrahydrofuran at 20℃; for 6h;	83%
With hydrogenchloride
With sulfuric acid

4-Ethoxyaniline (156-43-4) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
Stage #1: 4-Ethoxyaniline With acetic anhydride; triethylamine In dichloromethane at 0 - 20℃; Stage #2: With nitric acid In dichloromethane at 0 - 20℃; Stage #3: With sodium hydride In tetrahydrofuran; methanol; mineral oil at 20℃;	83%
Multi-step reaction with 2 steps 1: diethyl ether; potassium ethoxide View Scheme

4-hydroxy-2-nitroaniline (610-81-1) + ethyl iodide (75-03-6) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
With lithium hydroxide monohydrate In ethanol at 60℃;	75%
With potassium carbonate In hexane; ethyl acetate; acetonitrile	50.8%

N-nitro-p-phenetidine → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
With sodium hydroxide
With sulfuric acid

chloro-acetic acid-(4-ethoxy-2-nitro-anilide) (380195-34-6) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
With potassium hydroxide

lactic acid-(4-ethoxy-2-nitro-anilide) (329063-81-2) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
With potassium hydroxide

methanesulfonic acid-(4-ethoxy-2-nitro-anilide) (108142-81-0) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
With sulfuric acid

ethanesulfonic acid-(4-ethoxy-2-nitro-anilide) (901285-90-3) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
With sulfuric acid

2-nitro-toluene-4-sulfonic acid-(4-ethoxy-2-nitro-anilide) (861560-26-1) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
With sulfuric acid at 60 - 70℃;

ethanol (64-17-5) + N-(4-ethoxy-2-nitrophenyl)acetamide (885-81-4) + nitric acid (7697-37-2) → 2-nitro-4-ethoxyaniline (616-86-4)

nitrohydroquinone-diethyl ether → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
With ammonia; water at 130 - 140℃;

lactic acid-(4-ethoxy-2-nitro-anilide) (329063-81-2) + alcoholic KOH-solution → 2-nitro-4-ethoxyaniline (616-86-4)

N-nitro-p-phenetidine + aqueous NaOH-solution → 2-nitro-4-ethoxyaniline (616-86-4)

chloro-acetic acid-(4-ethoxy-2-nitro-anilide) (380195-34-6) + diluted KOH-solution → 2-nitro-4-ethoxyaniline (616-86-4)

4-ethoxyacetanilide (62-44-2) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: HNO3; AcOH / 5 - 20 °C 2: aq. H2SO4 / 70 - 80 °C View Scheme
Multi-step reaction with 2 steps 1: nitric acid / durch allmaehliches Hinzufuegen von konz.Salpetersaeure in geringem Ueberschuss 2: alcoholic potash View Scheme
Multi-step reaction with 2 steps 1: acetic acid; nitric acid / <12 2: diluted aqueous hydrochloric acid View Scheme
Multi-step reaction with 2 steps 1: alcohol; nitric acid / <25 / anschliessendes kurzes Erwaermen auf 40-60grad 2: alcohol; nitric acid View Scheme
Multi-step reaction with 2 steps 1: acetic acid; nitric acid 2: aq.-ethanolic NaOH-solution View Scheme

methanesulfonic acid p-phenetidide (10406-66-3) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: alcohol; nitric acid 2: concentrated sulfuric acid View Scheme
Multi-step reaction with 2 steps 1: alcohol; nitric acid 2: concentrated sulfuric acid View Scheme

2-nitro-toluene-4-sulfonic acid p-phenetidide (349099-73-6) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: alcohol; nitric acid 2: concentrated sulfuric acid / 60 - 70 °C View Scheme
Multi-step reaction with 2 steps 1: glacial acetic acid; nitric acid / 14 - 24 °C 2: concentrated sulfuric acid / 60 - 70 °C View Scheme

ethyl bromide (74-96-4) + 4-hydroxy-2-nitroaniline (610-81-1) → 2-nitro-4-ethoxyaniline (616-86-4)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 52h;

thiophosgene (463-71-8) + 2-nitro-4-ethoxyaniline (616-86-4) → 4-ethoxy-2-nitro-phenyl isothiocyanate (87200-45-1)

Conditions	Yield
In ethyl acetate at 75℃; for 1h;	97%
With water
With hydrogenchloride; acetic acid In chloroform Yield given;

propan-1-ol (71-23-8) + 2-nitro-4-ethoxyaniline (616-86-4) → 5-ethoxy-2-ethylbenzimidazole

Conditions	Yield
With titanium(IV) oxide for 4h; Irradiation;	96%

2-nitro-4-ethoxyaniline (616-86-4) + 4-nitrobenzaldehdye (555-16-8) + phosphonic acid diethyl ester (762-04-9) → [(4-ethoxy-2-nitrophenylamino)-(4-nitrophenyl)-methyl]-phosphonic acid diethyl ester (1263200-41-4)

Conditions	Yield
With niobium pentachloride at 60℃; for 0.583333h; Kabachnik-Fields reaction; neat (no solvent);	95%

ethanol (64-17-5) + 2-nitro-4-ethoxyaniline (616-86-4) → 5-ethoxy-2-methyl-1(3)H-benzoimidazole (5895-31-8)

Conditions	Yield
With titanium(IV) oxide for 4h; Irradiation;	94%

2-nitro-4-ethoxyaniline (616-86-4) + phosphonic acid diethyl ester (762-04-9) + 2-nitro-benzaldehyde (552-89-6) → [(4-ethoxy-3-nitrophenylamino)-(2-nitrophenyl)-methyl]-phosphonic acid diethyl ester (1308428-35-4)

Conditions	Yield
With xanthan sulfuric acid at 60℃; for 1h; Neat (no solvent);	93%

2-nitro-4-ethoxyaniline (616-86-4) + 3-nitro-benzaldehyde (99-61-6) + phosphonic acid diethyl ester (762-04-9) → [(4-ethoxy-2-nitrophenylamino)-(3-nitrophenyl)-methyl]-phosphonic acid diethyl ester (1263200-42-5)

Conditions	Yield
With niobium pentachloride at 60℃; for 0.833333h; Kabachnik-Fields reaction; neat (no solvent);	86%

2-(3-ethoxyphenoxy)acetyl chloride (1446338-09-5) + 2-nitro-4-ethoxyaniline (616-86-4) → N-(4-ethoxy-2-nitrophenyl)-2-(3-ethoxyphenoxy)acetamide (1446338-10-8)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	80%

2-nitro-4-ethoxyaniline (616-86-4) + (halomethyl)benzene → N-benzyl-4-ethoxy-2-nitroaniline

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 70℃; for 6h;	78.9%

2-nitro-4-ethoxyaniline (616-86-4) + 5-(chloromethyl)-1,2,3-trimethoxybenzene (3840-30-0) → 4-ethoxy-2-nitro-N-(3,4,5-trimethoxybenzyl)aniline

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 70℃; for 6h;	75.3%

2-nitro-4-ethoxyaniline (616-86-4) + hydrocinnamic acid chloride (645-45-4) → N-(4-ethoxy-2-nitrophenyl)-3-phenylpropanamide (353783-49-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	70%

2-nitro-4-ethoxyaniline (616-86-4) + 4-chloro-benzoyl chloride (122-01-0) → 4-Chloro-N-(4-ethoxy-2-nitrophenyl)-benzoylamide

Conditions	Yield
With triethylamine In tetrahydrofuran Heating;	57%

2-Picolinic acid (98-98-6) + 2-nitro-4-ethoxyaniline (616-86-4) → N-(4-Ethoxy-2-nitrophenyl)-2-pyridinecarboxamide

Conditions	Yield
Stage #1: 2-Picolinic acid With 1,3,5-trichloro-2,4,6-triazine In tetrahydrofuran at 20℃; Stage #2: 2-nitro-4-ethoxyaniline With triethylamine In tetrahydrofuran Heating;	52%

6-Chloronicotinoyl chloride (58757-38-3) + 2-nitro-4-ethoxyaniline (616-86-4) → 6-chloro-N-(4-ethoxy-2-nitrophenyl)-3-pyridinecarboxamide (352228-42-3)

Conditions	Yield
With triethylamine In tetrahydrofuran Heating;	34%

6-methylnicotinic acid (3222-47-7) + 2-nitro-4-ethoxyaniline (616-86-4) → 6-Methyl-N-(4-ethoxy-2-nitrophenyl)-3-pyridinecarboxamide

Conditions	Yield
Stage #1: 6-methylnicotinic acid With 1,3,5-trichloro-2,4,6-triazine In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 2-nitro-4-ethoxyaniline With triethylamine In tetrahydrofuran for 20h; Heating;	32%

2-nitro-4-ethoxyaniline (616-86-4) + 5,7-dichloro-6-methylpyrazolo[1,5-a]pyrimidine (61098-38-2) → 5-chloro-N-(4-ethoxy-2-nitrophenyl)-6-methylpyrazolo[1,5-a]pyrimidin-7-amine

Conditions	Yield
With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 70℃; for 4h;	32%

5-ethylisoxazole-3-carbonyl azide (61672-69-3) + 2-nitro-4-ethoxyaniline (616-86-4) → N-(4-ethoxy-2-nitrophenyl)-N'-(5-ethylisoxazol-3-yl)urea

Conditions	Yield
In toluene at 70 - 100℃; for 38h;	28%

5-cyclopropylisoxazole-3-carbonyl azide (21080-83-1) + 2-nitro-4-ethoxyaniline (616-86-4) → N-(5-cyclopropylisoxazol-3-yl)-N'-(4-ethoxy-2-nitrophenyl)urea

Conditions	Yield
In toluene at 70 - 100℃; for 38h;	27%

maleic anhydride (108-31-6) + 2-nitro-4-ethoxyaniline (616-86-4) → N-(4-ethoxy-2-nitro-phenyl)-maleamic acid

succinic acid anhydride (108-30-5) + 2-nitro-4-ethoxyaniline (616-86-4) → N-(4-ethoxy-2-nitro-phenyl)-succinamic acid

Conditions	Yield
With xylene

phosgene (75-44-5) + 2-nitro-4-ethoxyaniline (616-86-4) → 4-ethoxy-1-isocyanato-2-nitrobenzene (108128-49-0)

phosgene (75-44-5) + 2-nitro-4-ethoxyaniline (616-86-4) → (4-ethoxy-2-nitro-phenyl)-urea

Conditions	Yield
With ammonia; toluene; benzene at 0℃;

2-nitro-4-ethoxyaniline (616-86-4) → 1-chloro-4-ethoxy-2-nitrobenzene (89979-06-6)

Conditions	Yield
Diazotization.Behandeln mit CuCl;

2-nitro-4-ethoxyaniline (616-86-4) → 4-ethoxy-benzene-1,2-diamine (1197-37-1)

Conditions	Yield
With ethanol; nickel Hydrogenation;
With hydrogenchloride; tin(ll) chloride
With hydrazine hydrate; nickel at 60 - 70℃; for 5h;

2-nitro-4-ethoxyaniline (616-86-4) → 1-bromo-4-ethoxy-2-nitrobenzene (139085-95-3)

Conditions	Yield
With sulfuric acid; sodium nitrite Erhitzen des Reaktionsgemisches mit Kupfer(I)-bromid und Bromwasserstoffsaeure;

2-nitro-4-ethoxyaniline (616-86-4) → 3,4-dinitro-phenetole

Conditions	Yield
With tetrafluoroboric acid; sodium nitrite Behandlung des gebildeten Diazoniumsalzes mit NaNO2 und Kupfer-Pulver in Wasser;

2-nitro-4-ethoxyaniline (616-86-4) → 1-ethoxy-3-nitrobenzene (621-52-3)

Upstream product

• 885-81-4 N-(4-ethoxy-2-nitrophenyl)acetamide 
• 380195-34-6 chloro-acetic acid-(4-ethoxy-2-nitro-anilide) 
• 329063-81-2 lactic acid-(4-ethoxy-2-nitro-anilide) 
• 901285-90-3 ethanesulfonic acid-(4-ethoxy-2-nitro-anilide) 
• 861560-26-1 2-nitro-toluene-4-sulfonic acid-(4-ethoxy-2-nitro-anilide) 
• 64-17-5 ethanol 
• 7697-37-2 nitric acid 
• 7664-93-9 sulfuric acid 
• 10406-66-3 methanesulfonic acid p-phenetidide 
• 349099-73-6 2-nitro-toluene-4-sulfonic acid p-phenetidide 
• 156-43-4 4-Ethoxyaniline 
• 74-96-4 ethyl bromide 
• 610-81-1 4-hydroxy-2-nitroaniline 
• 75-03-6 ethyl iodide 

Downstream Products

• 108128-49-0 4-ethoxy-1-isocyanato-2-nitrobenzene 
• 87200-45-1 4-ethoxy-2-nitro-phenyl isothiocyanate 
• 89979-06-6 1-chloro-4-ethoxy-2-nitrobenzene 
• 1197-37-1 4-ethoxy-benzene-1,2-diamine 
• 139085-95-3 1-bromo-4-ethoxy-2-nitrobenzene 
• 621-52-3 1-ethoxy-3-nitrobenzene 
• 282547-59-5 6-ethoxy-8-nitro-quinoline 
• 109321-58-6 2-(4-Ethoxy-2-nitro-phenylazo)-3-oxo-butyric acid ethyl ester 
• 109321-63-3 4-[(4-Ethoxy-2-nitro-phenyl)-hydrazono]-5-methyl-2,4-dihydro-pyrazol-3-one 
• 32387-94-3 2,3-diphenyl-6-ethoxyquinoxaline 
• 352228-42-3 6-chloro-N-(4-ethoxy-2-nitrophenyl)-3-pyridinecarboxamide 
• 72546-10-2 4-ethoxy-2-nitrobenzenesulfonyl chloride 
• 109321-77-9 4-[(4-Ethoxy-2-nitro-phenyl)-hydrazono]-2-hydroxymethyl-5-methyl-2,4-dihydro-pyrazol-3-one 
• 109321-65-5 2-Benzenesulfonyl-4-[(4-ethoxy-2-nitro-phenyl)-hydrazono]-5-methyl-2,4-dihydro-pyrazol-3-one 

Relevant articles and documents

ARYLCARBOXAMIDES AND USES THEREOF

The present disclosure is directed to compounds of formula (I): or a pharmaceutically acceptable salt, solvate or solvate of the salt thereof. Compounds of formula (I) are inhibitors of NOX4 and are useful in the treatment of fibrotic diseases such as scleroderma; lung disease, such as pulmonary fibrosis including idiopathic pulmonary fibrosis (IPF); heart disease, such as heart failure due to ischaemic heart disease, valvular heart disease and hypertensive heart disease, diabetic cardiomyopathy and hypertension; liver disease, such as cirrhosis of the liver; and kidney disease, such as progressive kidney disease glomerulonephritis and diabetic nephropathy; and eye disease such as diabetic retinopathy; skin or subcutaneous scarring, such as keloids, adhesions, hypertrophic scarring or cosmetic scarring; or as an adjuvant or anti-fibrotic in pancreatic cancer to increase chemotherapeutic drug penetration by reducing the density of the connective tissue stroma.

Indole and indazole compounds as an inhibitor of cellular necrosis

The present invention refers to a formula (1) compounds of, pharmaceutically acceptable salts or isomers thereof thereof, and characterized by by containing as active ingredients-associated diseases, cell death and method for the prevention or treatment of relates and compositions. [Formula 1] In formula said R 1, R 2, R 3, R 4, R 5, R 6, A, X, n and m to equal the specification.

HEPATITIS C VIRUS INHIBITORS

Hepatitis C virus inhibitors having the general formula (I) are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

BENZIMIDAZOLE DERIVATIVES AS SELECTIVE BLOCKERS OF PERSISTENT SODIUM CURRENT

The present invention is directed to a compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein R, R1, R2, R3, R4, m, and n are as defined herein, to pharmaceutical compositions comprising said compound, and to methods of treating diseases or conditions mediated by elevated persistent sodium current, such as an ocular disorder, multiple sclerosis, seizure disorder, and chronic pain.

INDOLE AND INDAZOLE COMPOUNDS AS AN INHIBITOR OF CELLULAR NECROSIS

The present invention relates to indole or indazole compounds, pharmaceutically acceptable salts or isomers thereof which are useful for the prevention or treatment of cellular necrosis and necrosis-associated diseases. The present invention also relates to a method and a composition for the prevention or treatment of cellular necrosis and necrosis-associated diseases, comprising said indole or indazole compounds as an active ingredient.

INDOLE AND INDAZOLE DERIVATIVES HAVING A CELL-, TISSUE- AND ORGAN-PRESERVING EFFECT

The present invention relates to a composition for preserving cells, tissues and organs, comprising as an active ingredient indole and indazole compounds of formula (1), or a pharmaceutically acceptable salt or isomer thereof, which are effective for preventing injury of organs, isolated cell systems or tissues caused by cold storage, transplant operation or post-transplantation reperfusion; a preservation method; and a preparation method of the composition.

GLUCOKINASE ACTIVATORS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AS AN ACTIVE INGREDIENT

The present invention relates to new compounds of formula (1) exhibiting excellent activity for glucokinase, and pharmaceutical compositions comprising the same as an active ingredient.

INDOLE AND INDAZOLE COMPOUNDS AS AN INHIBITOR OF CELLULAR NECROSIS

The present invention relates to indole or indazole compounds, pharmaceutically acceptable salts or isomers thereof which are useful for the prevention or treatment of cellular necrosis and necrosis-associated diseases. The present invention also relates to a method and a composition for the prevention or treatment of cellular necrosis and necrosis-associated diseases, comprising said indole or indazole compounds as an active ingredient.

GLUCOKINASE ACTIVATORS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AS AN ACTIVE INGREDIENT

The present invention relates to new compounds of formula (1) exhibiting excellent activity for glucokinase, and pharmaceutical compositions comprising the same as an active ingredient.

INDOLE COMPOUNDS AS AN INHIBITOR OF CELLULAR NECROSIS

The present invention relates to new indole compounds, pharmaceutically acceptable salts or isomers thereof which are useful for the prevention or treatment of cellular necrosis and necrosis-associated diseases. The present invention also relates to a method and a composition for the prevention or treatment of cellular necrosis and necrosis-associated diseases, comprising said indole compounds as an active ingredient.