15308-01-7

Basic information

• Product Name: 2-chloro-N-(2,6-dichlorophenyl)-N-phenylacetamide
• Synonyms: N-Chloro Acetyl-2,6 Dichloro Diphenyl Amine;N-(2,6-DICHLOROPHENYLACETANILIDE;2,2',6'-Trichloro-N-phenylacetanilide;N-(2,6-Dichlorophenyl)-N-phenylchloroacetamide;N-(2,6-Dichlorophenyl)-α-chloroacetanilide;Einecs 239-350-6;Diclofenac Related Compound (N-Chloroacetyl-N-phenyl-2,6-dichloroaniline);Diclofenac Chloroacetyl Impurity
• CAS NO: 15308-01-7
• Molecular Formula: C₁₄H₁₀Cl₃NO
• Molecular Weight: 314.5943
• EINECS: 239-350-6
• Mol File: 15308-01-7.mol

Chemical Properties

• Melting Point: 143-144 °C(Solv: water (7732-18-5); ethanol (64-17-5))
• Boiling Point: 487.5 °C at 760 mmHg
• Flash Point: 248.6 °C
• Appearance: White to off white crystalline powder
• Density: 1.411 g/cm³
• Vapor Pressure: 1.18E-09mmHg at 25°C
• Refractive Index: 1.633
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -5.47±0.50(Predicted)
• CAS DataBase Reference: 2-chloro-N-(2,6-dichlorophenyl)-N-phenylacetamide(CAS DataBase Reference)
• NIST Chemistry Reference: 2-chloro-N-(2,6-dichlorophenyl)-N-phenylacetamide(15308-01-7)
• EPA Substance Registry System: 2-chloro-N-(2,6-dichlorophenyl)-N-phenylacetamide(15308-01-7)

Safety Data

• Hazardous Substances Data: 15308-01-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-chloro-N-(2,6-dichlorophenyl)-N-phenylacetamide is used as a reactant for the preparation of 1-(2,6-dichlorophenyl)-3-methylene-1,3-dihydro-indol-2-one derivatives. These derivatives exhibit in vitro cytotoxic activity on SW620 colon cancer cell lines, making them promising candidates for the development of novel anticancer drugs.

InChI:InChI=1/C14H10Cl3NO/c15-9-13(19)18(10-5-2-1-3-6-10)14-11(16)7-4-8-12(14)17/h1-8H,9H2

Synthetic route

N-phenyl-2,6-dichloroaniline (15307-93-4) + chloroacetyl chloride (79-04-9) → 2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7)

Conditions	Yield
at 106 - 110℃; for 2h; Acetylation;	86%
for 16h; Heating;	66%
for 5h; Reflux;
for 5h; Reflux;
In toluene at 120℃; for 3h; Solvent;

2,2,6,6-tetrachlorocyclohexanone (3776-30-5) → 2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 99 percent / TiCl4 / toluene / 2 h / 20 °C 2: Et3N / dimethylformamide / 5 h / 95 - 100 °C 3: 86 percent / 2 h / 106 - 110 °C View Scheme

aniline (62-53-3) + Wang resin-bound styrene 4 → 2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 99 percent / TiCl4 / toluene / 2 h / 20 °C 2: Et3N / dimethylformamide / 5 h / 95 - 100 °C 3: 86 percent / 2 h / 106 - 110 °C View Scheme

N-phenyl-2,2,6,6-tetrachlorocyclohexaneimine (123066-65-9) → 2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / dimethylformamide / 5 h / 95 - 100 °C 2: 86 percent / 2 h / 106 - 110 °C View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-(2,6-dichlorophenyl)indolin-2-one (15362-40-0)

Conditions	Yield
With aluminium trichloride at 160℃; for 2h;	75.4%
With aluminum (III) chloride at 160℃; for 2h;	62%
With aluminum (III) chloride at 160℃; for 2h;
With triethylamine hydrochloride-aluminum trichloride at 20 - 60℃; for 4.5h; Reagent/catalyst;

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → diclofenac sodium (15307-79-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75.4 percent / AlCl3 / 2 h / 160 °C 2: 93 percent / 2 N NaOH / ethanol; H2O / 4 h / Heating View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(4-chlorophenyl)]methylene}-1,3-dihydroindol-2-one (1146981-11-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(4-fluorophenyl)]methylene}-1,3-dihydroindol-2-one (1146981-16-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(4-hydroxyphenyl)]methylene}-1,3-dihydroindol-2-one (1146981-19-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(4-(dimethylamino)phenyl)]methylene}-1,3-dihydroindol-2-one (145253-61-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(3-chlorophenyl)]methylene}-1,3-dihydroindol-2-one (1146981-10-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-(2,6-dichlorophenyl)-3-(3-bromobenzylidene)-1,3-dihydroindol-2-one (1146981-17-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(3-phenoxyphenyl)]methylene}-1,3-dihydroindol-2-one (1146981-18-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-(2,6-dichlorophenyl)-3-((2,6-dichlorophenyl)methylene)-1,3-dihydroindol-2-one (1146981-13-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(2-chloroquinolin-3-yl)]methylene}-1,3-dihydroindol-2-one (1146981-23-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(2-chloro-6-methylquinolin-3-yl)]methylene}-1,3-dihydroindol-2-one (1146981-24-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → C26H17Cl3N2O (1146981-25-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(furan-2-yl)]methylene}-1,3-dihydro-indol-2-one (1146981-22-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-(2,6-dichlorophenyl)-3-((phenyl)methylene)-1,3-dihydroindol-2-one (15307-68-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(2-chlorophenyl)]methylene}-1,3-dihydroindol-2-one (1146981-09-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(2-nitrophenyl)]methylene}-1,3-dihydroindol-2-one (1146981-15-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(3,4-dimethoxyphenyl)]methylene}-1,3-dihydroindol-2-one (1146981-20-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

2-chloro-N-(2',6'-dichlorophenyl)-N-phenylacetamide (15308-01-7) → 1-{[(2,6-dichlorophenyl)-3-(naphthalen-1-yl)]methylene}-1,3-dihydroindol-2-one (1146981-21-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 2 h / 160 °C 2: piperidine / ethanol / Reflux; Inert atmosphere View Scheme

Upstream product

• 587-65-5 N-chloroacetyl-aniline 
• 62-53-3 aniline 
• 3776-30-5 2,2,6,6-tetrachlorocyclohexanone 
• 15307-93-4 N-phenyl-2,6-dichloroaniline 
• 79-04-9 chloroacetyl chloride 
• 123066-65-9 N-phenyl-2,2,6,6-tetrachlorocyclohexaneimine 

Downstream Products

• 1146981-21-6 1-{[(2,6-dichlorophenyl)-3-(naphthalen-1-yl)]methylene}-1,3-dihydroindol-2-one 
• 1146981-20-5 1-{[(2,6-dichlorophenyl)-3-(3,4-dimethoxyphenyl)]methylene}-1,3-dihydroindol-2-one 
• 1146981-15-8 1-{[(2,6-dichlorophenyl)-3-(2-nitrophenyl)]methylene}-1,3-dihydroindol-2-one 
• 1146981-09-0 1-{[(2,6-dichlorophenyl)-3-(2-chlorophenyl)]methylene}-1,3-dihydroindol-2-one 
• 15307-68-3 1-(2,6-dichlorophenyl)-3-((phenyl)methylene)-1,3-dihydroindol-2-one 
• 1146981-22-7 1-{[(2,6-dichlorophenyl)-3-(furan-2-yl)]methylene}-1,3-dihydro-indol-2-one 
• 1146981-25-0 C₂₆H₁₇Cl₃N₂O 
• 1146981-24-9 1-{[(2,6-dichlorophenyl)-3-(2-chloro-6-methylquinolin-3-yl)]methylene}-1,3-dihydroindol-2-one 
• 1146981-23-8 1-{[(2,6-dichlorophenyl)-3-(2-chloroquinolin-3-yl)]methylene}-1,3-dihydroindol-2-one 
• 1146981-13-6 1-(2,6-dichlorophenyl)-3-((2,6-dichlorophenyl)methylene)-1,3-dihydroindol-2-one 
• 1146981-18-1 1-{[(2,6-dichlorophenyl)-3-(3-phenoxyphenyl)]methylene}-1,3-dihydroindol-2-one 
• 1146981-17-0 1-(2,6-dichlorophenyl)-3-(3-bromobenzylidene)-1,3-dihydroindol-2-one 
• 1146981-10-3 1-{[(2,6-dichlorophenyl)-3-(3-chlorophenyl)]methylene}-1,3-dihydroindol-2-one 
• 145253-61-8 1-{[(2,6-dichlorophenyl)-3-(4-(dimethylamino)phenyl)]methylene}-1,3-dihydroindol-2-one 

Relevant articles and documents

Synthesis method of diclofenac sodium

The invention discloses a synthesis method of diclofenac sodium, which comprises the following steps: (1) toluene. An oil layer is obtained by adding 2, 6 -dichlorophenol and sodium carbonate, keeping warm and refluxing, extracting the oil layer with water, and adding an alkali heat-preserving reaction in the oil layer to obtain 2, 6 -dichloroaniline. (2) 1, 2 Dichlorodimethylaniline prepared in step (6 -) is heated and melted, chloroacetyl chloride is added dropwise, and the heat is subjected to heat preservation reaction after being heated to crystallize to obtain N - (2, 6 - dichlorophenyl) - phenyl - chloroacetamide. (3) 2 (N - 2 Dichlorophenyl) 6 - phenyl - chloroacetamide prepared in step (-) is reacted with the aluminum trichloride to give a solid 1 - (2, 6 -dichlorophenyl) -2 -indolinone. (4) 3 (1 - 2-dichlorophenyl) 6 -indolinone prepared in step (-2 -) is added to alkali liquor, stirred and heated to reflux to obtain diclofenac sodium. The synthesis method is stable, easy to operate, low in cost, high in yield and suitable for industrial production.

Preparation method of 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate

The invention belongs to the field of chemical pharmacy, and relates to a production process of a chemical bulk drug, in particular to a preparation method of 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate. The preparation method comprises the following steps: taking 2, 6-dichlorodiphenylamine and chloroacetyl chloride as initial raw materials; and completing acylation reaction, Lewis acidicionic liquid catalyzed Friedel-Crafts alkylation reaction and hydrolysis reaction by a one-pot method to finally obtain the 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate. The 2-[(2,6-dichlorophenyl) amino] sodium phenylacetate is synthesized by adopting a one-pot preparation scheme, has the advantages of short reaction time, simplicity in operation, mild conditions, high yield, good catalytic effect, high selectivity, recyclability and the like, and is beneficial to industrial production.

In vitro cytotoxicity evaluation of diversely substituted N-aryl-2-oxindoles

In continuation with our previous work, structurally diverse 2-indolinones bearing 2,6-dichloroaryl fragment at N 1 and (hetero)aryl benzylidene at C3 were evaluated for their antitumor activity on a panel of cancer cell lines such as MCF-7 (breast), MiapaCa2 (pancreas), KB (oral), HuTu80 (stomach), L132 (lung), B16F10 (melanoma), and Molt4 (leukemia) from various human organs. Among the screened compound library, molecules 4e, 4k, and 4r have shown excellent cytotoxicity on a stomach cancer cell line. Moreover, a significant number of compounds have also shown promising cytotoxicity on pancreas and oral cancer cell lines.

Synthesis of 1-(2,6-dichlorophenyl)-3-methylene-1,3-dihydro-indol-2-one derivatives and in vitro anticancer evaluation against SW620 colon cancer cell line

A small library of 2-indolinone derivatives with the 2,6-dichlorophenyl ring at the N1 position and with varying substitutions including aryl groups at the 3-position were synthesized, and their structures were confirmed by spectral analysis. All molecules were screened for their in vitro cytotoxic activity on SW620 colon cancer cell lines. Among the designed series compounds 4c, 4f and 4j were found to be active at concentrations of 2-15 μg/ml. Some 3D-QSAR models were also built to understand the structure-activity relationship.

Synthesis and quantitative structure-activity relationships of diclofenac analogues

The synthesis of a series of 2-anilinophenylacetic acid, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.