77668-42-9

Basic information

• Product Name: 2,3-Dichlorobenzoylcyanide
• Synonyms: 2-(2,3-Dichlorophenyl)-2-oxoacetonitrile;2,3-DICHLOROBENZOYL CYANIDE;(2,3-dichlorophenyl)oxoacetonitrile;2,3-DichloroBenzoylNitrile;2,3-dichlorobenozyl cyanide;2,3-Dichloro-α-oxobenzeneacetonitrile;2,3-Dichlorobenzoylc;2-(2,3-Dichlorophenyl)-2-oxoacetonitrile (2,3-Dichlorobenzoyl Nitrile)
• CAS NO: 77668-42-9
• Molecular Formula: C₈H₃Cl₂NO
• Molecular Weight: 200.02
• EINECS: 278-747-9
• Product Categories: Nitriles;Lamotrigine
• Mol File: 77668-42-9.mol
• Article Data: 11

Chemical Properties

• Melting Point: 52-53 °C(Solv: ligroine (8032-32-4))
• Boiling Point: 309°C
• Flash Point: 141°C
• Appearance: /
• Density: 1.446
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 2,3-Dichlorobenzoylcyanide(CAS DataBase Reference)
• NIST Chemistry Reference: 2,3-Dichlorobenzoylcyanide(77668-42-9)
• EPA Substance Registry System: 2,3-Dichlorobenzoylcyanide(77668-42-9)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 77668-42-9(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

2,3-Dichlorobenzoyl cyanide is an impurity of Lamotrigine (L173250), an anticonvulsant that is used in the treatment of bipolar and depression.

InChI:InChI=1/C8H3Cl2NO/c9-6-3-1-2-5(8(6)10)7(12)4-11/h1-3H

Synthetic route

2,3-dichlorobenzoyl chloride (2905-60-4) + copper(I) cyanide (544-92-3) → 2,3-dichlorobenzoyl cyanide (77668-42-9)

Conditions	Yield
at 160 - 165℃; for 7h;	94.2%
at 35 - 165℃; for 4h; Product distribution / selectivity;	74%
With potassium iodide In chlorobenzene at 132 - 135℃; for 6h;

2,3-dichlorobenzoyl chloride (2905-60-4) + copper(l) cyanide → 2,3-dichlorobenzoyl cyanide (77668-42-9)

Conditions	Yield
With potassium iodide In toluene for 1h; Inert atmosphere; Reflux;	84%
With cetyltrimethylammonim bromide In toluene at 110℃; for 12h; Kinetics; Reagent/catalyst; Solvent; Large scale;	77%
at 160℃; for 6h;

2,3-dichlorobenzoyl chloride (2905-60-4) + sodium cyanide (143-33-9) → 2,3-dichlorobenzoyl cyanide (77668-42-9)

Conditions	Yield
With copper(l) iodide In acetonitrile at 20℃; for 6 - 9h;	80%

2,3-dichlorobenzoyl chloride (2905-60-4) + copper(I) cyanide (544-92-3) → 2,3-dichlorobenzoyl cyanide (77668-42-9) + 2,3-dichlorobenzoic acid anhydride (252186-80-4)

Conditions	Yield
at 35 - 165℃; for 6h; Product distribution / selectivity;	A 57% B 6.9%

2,3-dichlorobenzoyl chloride (2905-60-4) → 2,3-dichlorobenzoyl cyanide (77668-42-9)

Conditions	Yield
With copper(l) cyanide at 160 - 165℃; for 6h;

2,3-dichlorbenzoic acid (50-45-3) → 2,3-dichlorobenzoyl cyanide (77668-42-9)

Conditions	Yield
With thionyl chloride; mercury
Multi-step reaction with 2 steps 1: thionyl chloride / 2 h / Inert atmosphere; Reflux 2: cetyltrimethylammonim bromide / toluene / 12 h / 110 °C / Large scale View Scheme
Multi-step reaction with 2 steps 1: thionyl chloride / 6 h 2: 6 h / 160 °C View Scheme

2,3-dichlorobenzoyl chloride (2905-60-4) + sodium cyanide (143-33-9) + copper(I) cyanide (544-92-3) → 2,3-dichlorobenzoyl cyanide (77668-42-9) + 2,3-dichlorobenzoic acid anhydride (252186-80-4)

Conditions	Yield
at 35 - 165℃; for 10h; Product distribution / selectivity;

2,3-dichlorbenzoic acid (50-45-3) + copper(l) cyanide → 2,3-dichlorobenzoyl cyanide (77668-42-9)

Conditions	Yield
Stage #1: 2,3-dichlorbenzoic acid With thionyl chloride Stage #2: copper(l) cyanide

sodium cyanide (773837-37-9) + 2,3-dichlorobenzoyl chloride (2905-60-4) → 2,3-dichlorobenzoyl cyanide (77668-42-9) + 2,3-dichlorobenzoic acid anhydride (252186-80-4) + 2,3-dichlorbenzoic acid (50-45-3) + C16H6Cl4N2O2

Conditions	Yield
With copper(l) chloride In para-xylene; acetonitrile Reagent/catalyst; Solvent;

2,3-dichlorobenzoyl cyanide (77668-42-9) + aminoguanidine bicarbonate (2582-30-1) → 2-(2,3-dichlorophenyl)-2-(aminoguanidine)-acetonitrile

Conditions	Yield
With methanesulfonic acid at 45℃; for 5h; Heating / reflux;	82%
With methanesulfonic acid In toluene at 45℃; for 10h; Heating / reflux;	79%
Stage #1: aminoguanidine bicarbonate With sulfuric acid In water at 25℃; for 0.5h; Stage #2: 2,3-dichlorobenzoyl cyanide In water at 60℃; for 6h; Stage #3: With sodium hydroxide; water at 25 - 60℃; for 1h; Product distribution / selectivity;	76.8%

2,3-dichlorobenzoyl cyanide (77668-42-9) + 3-phenylimino-2-indolinone (33828-98-7, 101671-27-6) → 2‐oxo‐3‐(phenylamino)indoline‐3‐carbonitrile (32816-69-6)

Conditions	Yield
In methanol at 20℃; for 12h;	80%

2,3-dichlorobenzoyl cyanide (77668-42-9) + aminoguanidine bicarbonate (2582-30-1) → 2-(2,3-dichlorophenyl)-2-(guanidinylamino)acetonitrile

Conditions	Yield
Stage #1: 2,3-dichlorobenzoyl cyanide; aminoguanidine bicarbonate With sulfuric acid In water at 55 - 60℃; for 6h; Stage #2: With sodium hydroxide In water at 20℃; for 0.5h; pH=9 - 10;	78%

2,3-dichlorobenzoyl cyanide (77668-42-9) → 2-(2,3-dichlorophenyl)-2-(guanidinoimino)acetonitrile (84689-20-3)

Conditions	Yield
Stage #1: 2,3-dichlorobenzoyl cyanide With sulfuric acid; aminoguanidine bicarbonate In water; acetonitrile at 25 - 50℃; for 30h; Stage #2: With ammonia; water pH=6 - 7; Stage #3: With sodium hydroxide; water at 15 - 25℃; pH=9.5 - 10;	70.3%

2,3-dichlorobenzoyl cyanide (77668-42-9) + aminoguanidine (79-17-4) → 2-(2,3-dichlorophenyl)-2-guanidinyliminoacetonitrile (84689-20-3)

Conditions	Yield
With PPA In 1,2-dimethoxyethane	67%

2,3-dichlorobenzoyl cyanide (77668-42-9) → (Z)-N-guanyl-2-(2,3-dichlorophenyl)-2-imino-acetonitrile sulfate

Conditions	Yield
Stage #1: aminoguanidine bicarbonate With sulfur trioxide In methanesulfonic acid at 20℃; for 0.333333h; Stage #2: 2,3-dichlorobenzoyl cyanide In methanesulfonic acid at 45℃; for 4h;

2,3-dichlorobenzoyl cyanide (77668-42-9) + aminoguanidinium tetrafluoroborate → (Z)-N-guanyl-2-(2,3-dichlorophenyl)-2-imino-acetonitrile tetrafluoroborate

Conditions	Yield
In diethyl ether; acetonitrile at 45℃; for 4h; Product distribution / selectivity;

2,3-dichlorobenzoyl cyanide (77668-42-9) + aminoguanidinium tetrafluoroborate → lamotrigine (84057-84-1)

Conditions	Yield
Stage #1: 2,3-dichlorobenzoyl cyanide; aminoguanidinium tetrafluoroborate In diethyl ether; acetonitrile at 45℃; for 4h; Stage #2: With sodium hydroxide In diethyl ether; water; acetonitrile at 50 - 70℃; for 1h; pH=> 12; Product distribution / selectivity;

tetrafluoroboric acid + 2,3-dichlorobenzoyl cyanide (77668-42-9) → (Z)-N-guanyl-2-(2,3-dichlorophenyl)-2-imino-acetonitrile tetrafluoroborate

Conditions	Yield
Stage #1: tetrafluoroboric acid; aminoguanidine bicarbonate In water; acetonitrile at 15 - 30℃; for 0.166667 - 0.5h; Stage #2: 2,3-dichlorobenzoyl cyanide In water; acetonitrile at 45℃; for 5 - 6h; Product distribution / selectivity;

2,3-dichlorobenzoyl cyanide (77668-42-9) + aminoguanidine bismesylate → lamotrigine (84057-84-1)

Conditions	Yield
Stage #1: 2,3-dichlorobenzoyl cyanide; aminoguanidine bismesylate With methanesulfonic acid In acetonitrile at 65 - 70℃; for 1h; Stage #2: With magnesium oxide In water; acetonitrile at 70℃; for 3.16667h;

2,3-dichlorobenzoyl cyanide (77668-42-9) → lamotrigine (84057-84-1)

Conditions	Yield
With potassium hydroxide
With potassium hydroxide
Stage #1: aminoguanidine bicarbonate With sulfur trioxide In methanesulfonic acid at 25℃; for 1h; Stage #2: 2,3-dichlorobenzoyl cyanide In methanesulfonic acid at 45℃; for 5h; Stage #3: With sodium hydroxide In methanesulfonic acid; water; acetonitrile at 20 - 70℃; for 3.5h; pH=> 12; Product distribution / selectivity;

2,3-dichlorobenzoyl cyanide (77668-42-9) + aminoguanidine bicarbonate (2582-30-1) → 2-(2,3-dichlorophenyl)-2-guanidinyliminoacetonitrile (84689-20-3)

Conditions	Yield
Stage #1: aminoguanidine bicarbonate With sulfuric acid; toluene-4-sulfonic acid In toluene at 110℃; for 0.25h; Stage #2: 2,3-dichlorobenzoyl cyanide In toluene at 80℃; for 3.5h; Heating / reflux;

2,3-dichlorobenzoyl cyanide (77668-42-9) + methanesulfonic acid (75-75-2) + aminoguanidine hydrogencarbonate (2200-97-7, 2582-30-1, 10587-01-6, 13998-67-9) → 2-(2,3-dichlorophenyl)-2-(aminoguanidine)-acetonitrile monomesylate

Conditions	Yield
Stage #1: methanesulfonic acid With phosphorus pentoxide for 2h; Stage #2: aminoguanidine hydrogencarbonate at 25 - 30℃; for 1h; Stage #3: 2,3-dichlorobenzoyl cyanide at 20℃; for 24h;

2,3-dichlorobenzoyl cyanide (77668-42-9) → methyl 2-(2,3-dichlorophenyl)-2-(2-p-tolylhydrazono)acetate

Conditions	Yield
Multi-step reaction with 3 steps 1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2: thionyl chloride / 4.5 h / 40 - 64 °C 3: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C View Scheme

2,3-dichlorobenzoyl cyanide (77668-42-9) → methyl 2-(2,3-dichlorophenyl)-2-(2-p-tolylhydrazono)acetate

Conditions	Yield
Multi-step reaction with 3 steps 1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2: thionyl chloride / 4.5 h / 40 - 64 °C 3: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C View Scheme

2,3-dichlorobenzoyl cyanide (77668-42-9) → 7-chloro-1-methyl-1H-indazole-3-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2.1: thionyl chloride / 4.5 h / 40 - 64 °C 3.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 4.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 95 - 100 °C 4.2: pH 2 - 2.5 View Scheme

2,3-dichlorobenzoyl cyanide (77668-42-9) → 7-chloro-1-ethyl-1H-indazole-3-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2.1: thionyl chloride / 4.5 h / 40 - 64 °C 3.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 4.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 7 h / 75 - 80 °C 4.2: pH 2 - 2.5 View Scheme

2,3-dichlorobenzoyl cyanide (77668-42-9) → 7-chloro-1-phenyl-1H-indazole-3-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2.1: thionyl chloride / 4.5 h / 40 - 64 °C 3.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 4.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 6 h / 75 - 80 °C 4.2: pH 2 - 2.5 View Scheme

2,3-dichlorobenzoyl cyanide (77668-42-9) → 7-chloro-1-(4-methoxyphenyl)-1H-indazole-3-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2.1: thionyl chloride / 4.5 h / 40 - 64 °C 3.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 4.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 6 h / 70 - 75 °C 4.2: pH 2 - 2.5 View Scheme

2,3-dichlorobenzoyl cyanide (77668-42-9) → 7-chloro-1-p-tolyl-1H-indazole-3-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2.1: thionyl chloride / 4.5 h / 40 - 64 °C 3.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 4.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 6 h / 75 - 80 °C 4.2: pH 2 - 2.5 View Scheme

2,3-dichlorobenzoyl cyanide (77668-42-9) → 7-chloro-1-(2,4-dichlorophenyl)-1H-indazole-3-carboxylic acid

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; sodium chloride; sulfuric acid / 1.5 h / 40 - 45 °C 2.1: thionyl chloride / 4.5 h / 40 - 64 °C 3.1: potassium carbonate / isopropyl alcohol / 6 h / 60 - 65 °C 4.1: L-proline; caesium carbonate; copper(l) iodide / dimethyl sulfoxide / 6 h / 95 - 100 °C 4.2: pH 2 - 2.5 View Scheme

Upstream product

• 50-45-3 2,3-dichlorbenzoic acid 
• 773837-37-9 sodium cyanide 
• 2905-60-4 2,3-dichlorobenzoyl chloride 
• 143-33-9 sodium cyanide 
• 544-92-3 copper(I) cyanide 

Downstream Products

• 84057-84-1 lamotrigine 
• 84689-20-3 2-(2,3-dichlorophenyl)-2-guanidinyliminoacetonitrile 
• 180868-97-7 2-(2,3-dichlorophenyl)-2-oxoacetamide 
• 1646328-15-5 (2,3-dichlorophenyl)-oxoacetic acid methyl ester 
• 32816-69-6 2‐oxo‐3‐(phenylamino)indoline‐3‐carbonitrile 
• 84689-20-3 2-(2,3-dichlorophenyl)-2-(guanidinoimino)acetonitrile 

Relevant articles and documents

An Evaluation of Multiple Catalytic Systems for the Cyanation of 2,3-Dichlorobenzoyl Chloride: Application to the Synthesis of Lamotrigine

2,3-Dichlorobenzoyl cyanide is a key intermediate in the synthesis of Lamotrigine. An assessment of various catalytic systems for the cyanation of 2,3-dichlorobenzoyl chloride with cyanide salts is described. High-throughput experimentation identified many conditions for effecting the requisite chemistry, including amine bases and phase-transfer catalysts, as well as catalyst-free conditions utilizing acetonitrile as a polar cosolvent. A novel catalyst, CuBr2, was identified by consideration of the possible oxidation of Cu(I) during high-throughput screening experimentation. CuCN was found to be the best cyanide source for achieving clean conversion; however, the solubility of CuCN was the major factor limiting reaction rate under many conditions. Improving CuCN solubility by using acetonitrile as solvent enhanced the reaction rate even in the absence of the catalysts tested but significantly complicated isolation of the product. With no acetonitrile cosolvent, phase-transfer catalysts such as tetrabutylammonium bromide (TBABr) are effective; however, use of TBABr led to inconsistent reaction profiles from run-to-run, due to an unexpected clumping of the CuCN solid. Switching to cetyltrimethylammonium bromide (CTAB) alleviated this clumping behavior, leading to consistent reactivity. This CTAB-catalyzed process was scaled up, giving 560 kg of 2,3-dichlorobenzoyl cyanide in 77% isolated yield.

Regioselective synthesis of 1-substituted indazole-3-carboxylic acids

In this article, we study the synthesis of 1-substituted indazole-3-carboxylic acids from 2-halobenzoic acids.

METHOD FOR PREPARING LAMOTRIGINE AND ITS INTERMEDIATE 2,3-DICHLOROBENZOYL CHLORIDE

The invention relates to an improved method for preparing 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine, also commonly known as lamotrigine. The present invention also relates to a method for preparing the intermediate 2,3-dichlorobenzoyl chloride, which comprises the synthesis by photochlorination of 2,3-dichlorobenzotrichloride followed by hydrolysis thereof. Said 2,3-dichlorobenzoyl chloride intermediate is useful for preparing lamotrigine.