2011-66-7

Basic information

• Product Name: 2-Amino-2'-chloro-5-nitro benzophenone
• Synonyms: 2-Amino-2'-chloro-5-Nitryl-diphenylmethanone;2-AMINO-5-NITRO-2''-CHLOROBENZOPHENONECLONAZAPAM;2-Amino-5-nitro-2'-chlorobenzophenone;(2-azanyl-5-nitro-phenyl)-(2-chlorophenyl)methanone;Clonazepam Related Compound B (25 mg) (2-Amino-2'-chloro-5-nitrobenzophenone);ClonazepaM USP Related CoMpound B;(2-Amino-5-nitrophenyl)(2-chlorophenyl)methanone, 2-(2-Chlorobenzoyl)-4-nitroaniline;ClonazepaM Related CoMpound B
• CAS NO: 2011-66-7
• Molecular Formula: C₁₃H₉ClN₂O₃
• Molecular Weight: 276.68
• EINECS: 217-929-4
• Product Categories: (intermediate of clonazepam,loprazolam);Amines;Aromatics;FINE Chemical & INTERMEDIATES;Aromatic Benzophenones & Derivatives (substituted)
• Mol File: 2011-66-7.mol
• Article Data: 8

Chemical Properties

• Melting Point: 119-121°C
• Boiling Point: 505.8 °C at 760 mmHg
• Flash Point: 259.7 °C
• Appearance: Pale yellow to yellow/Powder
• Density: 1.428 g/cm³
• Storage Temp.: Refrigerator, Under Inert Atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: -3.12±0.36(Predicted)
• Sensitive: Air Sensitive
• BRN: 2814216
• CAS DataBase Reference: 2-Amino-2'-chloro-5-nitro benzophenone(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Amino-2'-chloro-5-nitro benzophenone(2011-66-7)
• EPA Substance Registry System: 2-Amino-2'-chloro-5-nitro benzophenone(2011-66-7)

Safety Data

• Hazard Codes: Xi
• Statements: 46-36/37/38
• Safety Statements: 53-26-36/37-60
• Hazardous Substances Data: 2011-66-7(Hazardous Substances Data)

Usage

Description

2-Amino-2'-chloro-5-nitro benzophenone, also known as Clonazepam EP Impurity A, is a chemical compound with the molecular formula C13H8ClN3O2. It is a yellow crystal powder that is primarily recognized as an impurity in the pharmaceutical compound Clonazepam (C587080). 2-Amino-2'-chloro-5-nitro benzophenone has unique chemical properties that make it significant in the context of pharmaceutical manufacturing and quality control.

Uses

Used in Pharmaceutical Industry:
2-Amino-2'-chloro-5-nitro benzophenone is used as an impurity reference substance for Clonazepam. Its presence in Clonazepam is crucial for ensuring the quality, safety, and efficacy of the drug. By monitoring and controlling the levels of this impurity, pharmaceutical companies can maintain the desired standards for Clonazepam and minimize potential adverse effects on patients.
Used in Quality Control and Analysis:
In the field of pharmaceutical quality control and analysis, 2-Amino-2'-chloro-5-nitro benzophenone serves as a benchmark for identifying and quantifying impurities in Clonazepam. This helps in the development of accurate and reliable analytical methods, such as high-performance liquid chromatography (HPLC) and other chromatographic techniques, to assess the purity and potency of the drug.
Used in Research and Development:
2-Amino-2'-chloro-5-nitro benzophenone is also utilized in research and development for the study of its chemical properties, potential interactions with other compounds, and its role in the synthesis of related pharmaceuticals. Understanding the behavior of this impurity can contribute to the improvement of Clonazepam's manufacturing process and the development of new drugs with similar therapeutic properties.

Synthetic route

5-nitroanthranilonitrile (17420-30-3) + 2-Chlorobenzeneboronic acid (3900-89-8) → 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7)

Conditions	Yield
With 5,5'-dimethyl-2,2'-bipyridine; methanesulfonic acid; palladium(II) trifluoroacetate; water In 2-methyltetrahydrofuran at 100℃; for 36h; Reagent/catalyst; Solvent; Sealed tube; Inert atmosphere; Cooling with ice;	95%
With 5,5'-dimethyl-2,2'-bipyridine; methanesulfonic acid; palladium(II) trifluoroacetate In 2-methyltetrahydrofuran; water at 90℃; for 36h;

potassium (2-amino-5-nitrophenyl)trifluoroboranuide + o-chlorobenzoyl chloride (609-65-4) → 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0) In water; toluene at 90℃; for 12h; Reagent/catalyst; Temperature; Solvent;	94%

2-chloro-N-(4-nitrophenyl)benzamide (55501-45-6) + o-chlorobenzoyl chloride (609-65-4) → 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7)

Conditions	Yield
With sulfuric acid; acetic acid; zinc(II) chloride Yield given. Multistep reaction;

loprazolam (61197-73-7) → 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7)

Conditions	Yield
With hydrogenchloride for 2h; Heating;

5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one (364046-84-4, 364046-86-6) → 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7)

Conditions	Yield
With hydrogenchloride In ethanol Heating;

o-chlorobenzoyl chloride (609-65-4) + 4-nitro-aniline (100-01-6) → 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7)

Conditions	Yield
With zinc(II) chloride

2-amino-5-nitro-benzoic acid (616-79-5) → 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 12 h / Reflux 2: tetrahydrofuran / 0.33 h / Cooling with ice 3: hydrogenchloride / ethanol; water / Reflux View Scheme

2-methyl-6-nitro-4H-benzo[d][1,3]oxazin-4-one (10073-89-9) → 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran / 0.33 h / Cooling with ice 2: hydrogenchloride / ethanol; water / Reflux View Scheme

C15H11ClN2O4 → 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7)

Conditions	Yield
With hydrogenchloride In ethanol; water Reflux;	4.54 g

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) + 2-Bromoacetyl bromide (598-21-0) → 2-bromo-2'-(2-chlorobenzoyl)-4'-nitroacetanilide

Conditions	Yield
With sodium carbonate In dichloromethane for 0.166667h; Cooling with ice;	94%
With sodium carbonate In dichloromethane at 0 - 20℃; for 0.166667h;	93%
With sodium carbonate In dichloromethane for 0.166667h; Cooling with ice;	93%
In toluene for 0.025h; Microwave irradiation;	82%

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → (2-chloro-5-nitrophenyl)(2-chlorophenyl)methanone (54534-72-4)

Conditions	Yield
With copper dichloride; isopentyl nitrite In acetonitrile 1.) 65 deg C, 4 h, 2.) RT, overnight;	90%
With hydrogenchloride; copper(I) chloride In water; acetic acid; sodium nitrite

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) + ethyl acetoacetate (141-97-9) → 2-methyl-6-nitro-4-(2-nitro-phenyl)-quinoline-3-carboxylic acid ethyl ester

Conditions	Yield
With aminosulfonic acid at 70℃; for 1.5h; Friedlander condensation;	90%

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) + acetylacetone (123-54-6) → 1-[2-methyl-6-nitro-4-(2-nitro-phenyl)-quinolin-3-yl]-ethanone

Conditions	Yield
With aminosulfonic acid at 70℃; for 1.25h; Friedlander condensation;	85%

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) + cyclohexanone (108-94-1) → 7-nitro-9-(2-nitro-phenyl)-1,2,3,4-tetrahydro-acridine

Conditions	Yield
With aminosulfonic acid at 70℃; for 1h; Friedlander condensation;	82%

chloroacetaldehyde dimethyl acetal (97-97-2) + 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → 2-chloromethyl-4-o-chlorophenyl-1,2-dihydro-6-nitro-quinazoline 3-oxide (101945-55-5)

Conditions	Yield
With hydrogenchloride; hydroxylamine In ethanol; water 1.) 2 h; 2.) 2.5 h, reflux;	59%

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) + 2-(4-methylphenylsulfonamido)acetyl chloride (56218-62-3) → N-[2-(2-Chloro-benzoyl)-4-nitro-phenyl]-2-(toluene-4-sulfonylamino)-acetamide (80837-64-5)

Conditions	Yield
In acetone at 70℃;	53%

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) + 1-aminoguanidine hydrochloride (1937-19-5) → C14H13ClN6O2*ClH (136623-22-8)

Conditions	Yield
With hydrogenchloride In ethanol; water for 6h; Heating;	52%

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) + glycine ethyl ester hydrochloride (5680-79-5) → 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one (364046-84-4, 364046-86-6)

Conditions	Yield
With pyridine Reflux;	52%

1-(2-Methoxyphenyl)piperazine (35386-24-4) + 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → N-(2-(2-chlorobenzoyl)-4-nitrophenyl)-4-(2-methoxyphenyl)piperazine-1-carboxamide

Conditions	Yield
Stage #1: 2'-chloro-5-nitro-2-aminobenzophenone With pyridine; bis(trichloromethyl) carbonate In 1,2-dichloro-ethane at 90℃; for 1h; Inert atmosphere; Stage #2: 1-(2-Methoxyphenyl)piperazine In 1,2-dichloro-ethane for 4h; Inert atmosphere; Reflux;	40%

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) + 4-(3-methoxyphenyl)piperazine (16015-71-7) → N-(2-(2-chlorobenzoyl)-4-nitrophenyl)-4-(3-methoxyphenyl)piperazine-1-carboxamide

Conditions	Yield
Stage #1: 2'-chloro-5-nitro-2-aminobenzophenone With pyridine; bis(trichloromethyl) carbonate In 1,2-dichloro-ethane at 90℃; for 1h; Inert atmosphere; Stage #2: 4-(3-methoxyphenyl)piperazine In 1,2-dichloro-ethane for 4h; Inert atmosphere; Reflux;	40%

N-(benzyloxycarbonyl)glycyl chloride (15050-24-5) + 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → {[2-(2-Chloro-benzoyl)-4-nitro-phenylcarbamoyl]-methyl}-carbamic acid benzyl ester (76337-80-9)

Conditions	Yield
In N,N,N,N,N,N-hexamethylphosphoric triamide; acetonitrile Ambient temperature; Yield given;

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → 2-chloromethyl-4-o-chlorophenyl-6-nitro-quinazoline 3-oxide (101928-09-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 59 percent / NH2OH, 2 N HCl / ethanol; H2O / 1.) 2 h; 2.) 2.5 h, reflux 2: 75 percent / MnO2 / CH2Cl2 / 20 h / Ambient temperature View Scheme

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → 5-o-chlorophenyl-2-methylamino-7-nitro-3H-1,4-benzodiazepine-4-oxide (101928-10-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 59 percent / NH2OH, 2 N HCl / ethanol; H2O / 1.) 2 h; 2.) 2.5 h, reflux 2: 75 percent / MnO2 / CH2Cl2 / 20 h / Ambient temperature 3: 80 percent / methanol / 2 h / Ambient temperature View Scheme

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → 2-carboxymethylamino-5-o-chlorophenyl-7-nitro-3H-1,4-benzodiazepine 4-oxide (101928-12-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: 59 percent / NH2OH, 2 N HCl / ethanol; H2O / 1.) 2 h; 2.) 2.5 h, reflux 2: 75 percent / MnO2 / CH2Cl2 / 20 h / Ambient temperature 3: 80 percent / methanol / 2 h / Ambient temperature 4: 90 percent / imidazole / 48 h / Heating 5: 55 percent / 2 N NaOH / dimethylformamide / 5 °C View Scheme

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → 2-ethoxycarbonylmethylamino-5-o-chlorophenyl-1,3-dihydro-7-nitro-3H-1,4-benzodiazepine 4-oxide (101928-11-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 59 percent / NH2OH, 2 N HCl / ethanol; H2O / 1.) 2 h; 2.) 2.5 h, reflux 2: 75 percent / MnO2 / CH2Cl2 / 20 h / Ambient temperature 3: 80 percent / methanol / 2 h / Ambient temperature 4: 90 percent / imidazole / 48 h / Heating View Scheme

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → 6-o-chlorophenyl-2,4-dihydro-2-dimethylaminomethylene-8-nitro-1H-midazo<1,2-a><1,4>benzodiazepin-1-one-5-oxide (101928-13-6)

Conditions

Yield

Multi-step reaction with 6 steps 1: 59 percent / NH2OH, 2 N HCl / ethanol; H2O / 1.) 2 h; 2.) 2.5 h, reflux 2: 75 percent / MnO2 / CH2Cl2 / 20 h / Ambient temperature 3: 80 percent / methanol / 2 h / Ambient temperature 4: 90 percent / imidazole / 48 h / Heating 5: 55 percent / 2 N NaOH / dimethylformamide / 5 °C 6: 1.) dicyclohexylcarbodiimide; 2.) triethylamine / 1.) CH2Cl2, 1 h, RT; 2.) 2 h View Scheme

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → 6-o-chlorophenyl-2,4-dihydro-2(4-methyl-1-piperazinyl)methylene-8-nitro-1H-imidazo<1,2-a><1,4>benzodiazepin-1-one 5-oxide (101928-18-1)

Conditions

Yield

Multi-step reaction with 7 steps 1: 59 percent / NH2OH, 2 N HCl / ethanol; H2O / 1.) 2 h; 2.) 2.5 h, reflux 2: 75 percent / MnO2 / CH2Cl2 / 20 h / Ambient temperature 3: 80 percent / methanol / 2 h / Ambient temperature 4: 90 percent / imidazole / 48 h / Heating 5: 55 percent / 2 N NaOH / dimethylformamide / 5 °C 6: 1.) dicyclohexylcarbodiimide; 2.) triethylamine / 1.) CH2Cl2, 1 h, RT; 2.) 2 h 7: 70 percent / toluene / 9 h / Heating View Scheme

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → 6-o-chlorophenyl-2,4-dihydro-4-hydroxy-2-(4-methyl-1-piperazinyl)methylene-8-nitro-1H-imidazo<1,2-a><1,4>benzodiazepin-1-one (88968-21-2)

Conditions

Yield

Multi-step reaction with 8 steps 1: 59 percent / NH2OH, 2 N HCl / ethanol; H2O / 1.) 2 h; 2.) 2.5 h, reflux 2: 75 percent / MnO2 / CH2Cl2 / 20 h / Ambient temperature 3: 80 percent / methanol / 2 h / Ambient temperature 4: 90 percent / imidazole / 48 h / Heating 5: 55 percent / 2 N NaOH / dimethylformamide / 5 °C 6: 1.) dicyclohexylcarbodiimide; 2.) triethylamine / 1.) CH2Cl2, 1 h, RT; 2.) 2 h 7: 70 percent / toluene / 9 h / Heating 8: 67 percent / trifluoroacetic anhydride / CH2Cl2 / 0.25 h / Heating View Scheme

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → [5-Amino-2-(4-methyl-piperidin-1-yl)-phenyl]-(2-chloro-phenyl)-methanone (86187-94-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 90 percent / isoamyl nitrite, CuCl2 / acetonitrile / 1.) 65 deg C, 4 h, 2.) RT, overnight 2: 90 percent / K2CO3 / ethanol / 2 h / Heating 3: 50 percent / SnCl2, HCl View Scheme

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → [2-(4-methyl-1-piperidinyl)-5-nitrophenyl]-(2-chlorophenyl)-methanone (113456-71-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / isoamyl nitrite, CuCl2 / acetonitrile / 1.) 65 deg C, 4 h, 2.) RT, overnight 2: 90 percent / K2CO3 / ethanol / 2 h / Heating View Scheme

N-Cbz-Ala (1142-20-7) + 2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → (S)-benzyl-[1-[[2-(o-chlorobenzoyl)-4-nitrophenyl]carbamoyl]ethyl]carbamate (58662-82-1)

Conditions	Yield
With thionyl chloride; sodium hydrogencarbonate In tetrahydrofuran; Petroleum ether

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) + stannous chloride (7772-99-8) → 2,5-diamino-2'-chlorobenzophenone (58479-51-9)

Conditions	Yield
With sodium hydroxide In hydrogenchloride

2'-chloro-5-nitro-2-aminobenzophenone (2011-66-7) → 2-amino-2'-chloro-5-nitrobenzophenone hydrazone

Conditions	Yield
With hydrazine hydrate In diethylene glycol

Upstream product

• 609-65-4 o-chlorobenzoyl chloride 
• 10073-89-9 2-methyl-6-nitro-4H-benzo[d][1,3]oxazin-4-one 
• 616-79-5 2-amino-5-nitro-benzoic acid 
• 17420-30-3 5-nitroanthranilonitrile 
• 3900-89-8 2-Chlorobenzeneboronic acid 
• 100-01-6 4-nitro-aniline 
• 364046-84-4 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one 
• 61197-73-7 loprazolam 
• 55501-45-6 2-chloro-N-(4-nitrophenyl)benzamide 

Downstream Products

• 52130-87-7 2-bromo-2'-(2-chlorobenzoyl)-4'-nitroacetanilide 
• 364046-84-4 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one 
• 4959-17-5 7-Aminoclonazepam 
• 80080-94-0 (-)-benzyl-[1-[{2-(o-chlorobenzoyl)4-nitrophenyl}carbamoyl]-ethyl]carbamate 
• 58479-51-9 2,5-diamino-2'-chlorobenzophenone 
• 58662-82-1 (S)-benzyl-[1-[[2-(o-chlorobenzoyl)-4-nitrophenyl]carbamoyl]ethyl]carbamate 
• 88968-21-2 6-o-chlorophenyl-2,4-dihydro-4-hydroxy-2-(4-methyl-1-piperazinyl)methylene-8-nitro-1H-imidazo<1,2-a><1,4>benzodiazepin-1-one 
• 101928-18-1 6-o-chlorophenyl-2,4-dihydro-2(4-methyl-1-piperazinyl)methylene-8-nitro-1H-imidazo<1,2-a><1,4>benzodiazepin-1-one 5-oxide 
• 101928-13-6 6-o-chlorophenyl-2,4-dihydro-2-dimethylaminomethylene-8-nitro-1H-midazo<1,2-a><1,4>benzodiazepin-1-one-5-oxide 
• 101928-11-4 2-ethoxycarbonylmethylamino-5-o-chlorophenyl-1,3-dihydro-7-nitro-3H-1,4-benzodiazepine 4-oxide 
• 101928-12-5 2-carboxymethylamino-5-o-chlorophenyl-7-nitro-3H-1,4-benzodiazepine 4-oxide 
• 101928-10-3 5-o-chlorophenyl-2-methylamino-7-nitro-3H-1,4-benzodiazepine-4-oxide 
• 101928-09-0 2-chloromethyl-4-o-chlorophenyl-6-nitro-quinazoline 3-oxide 
• 80837-64-5 N-[2-(2-Chloro-benzoyl)-4-nitro-phenyl]-2-(toluene-4-sulfonylamino)-acetamide 

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