80194-70-3

Basic information

• Product Name: 2-Cyano-3-chloro-5-(trifluoromethyl)-pyridine
• Synonyms: 3-chloro-2-cyano-5-(trifluoromethyl)pyridine;3-Chloro-5-(trifluoroMethyl)picolinonitrile;3-Chloro-2-cyano-5-(trifluoromethyl)pyridine, 3-Chloro-5-(trifluoromethyl)picolinonitrile;3-Chloro-5-(Trifluoromethylpicolinonitr
• CAS NO: 80194-70-3
• Molecular Formula: C₇H₂ClF₃N₂
• Molecular Weight: 206.56
• Mol File: 80194-70-3.mol
• Article Data: 16

Chemical Properties

• Boiling Point: 250.4 °C at 760 mmHg
• Flash Point: 105.2 °C
• Appearance: /
• Density: 1.51 g/cm³
• Vapor Pressure: 0.0218mmHg at 25°C
• Refractive Index: 1.482
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -5.03±0.20(Predicted)
• CAS DataBase Reference: 2-Cyano-3-chloro-5-(trifluoromethyl)-pyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Cyano-3-chloro-5-(trifluoromethyl)-pyridine(80194-70-3)
• EPA Substance Registry System: 2-Cyano-3-chloro-5-(trifluoromethyl)-pyridine(80194-70-3)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 80194-70-3(Hazardous Substances Data)

Usage

General Description

2-Cyano-3-chloro-5-(trifluoromethyl)-pyridine, also known as CTFP, is a chemical compound with the formula C7H2ClF3N2. It is a pyridine derivative that contains a cyano, chloro, and trifluoromethyl group. CTFP is a highly versatile building block in organic synthesis, used for the production of various pharmaceuticals, agrochemicals, and materials. It has been employed in the synthesis of novel heterocyclic compounds with potential biological activities. CTFP is also used as an intermediate in the manufacturing of active pharmaceutical ingredients and is frequently employed in research and development laboratories for its unique chemical properties. Additionally, it is important to handle CTFP with caution as it is flammable and may cause skin and eye irritation.

InChI:InChI=1/C7H2ClF3N2/c8-5-1-4(7(9,10)11)3-13-6(5)2-12/h1,3H

Synthetic route

potassium cyanide + 2,3-dichloro-5-trifluoromethylpyridine (69045-84-7) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
Stage #1: 2,3-dichloro-5-trifluoromethylpyridine With dmap In acetone for 5h; Reflux; Large scale; Stage #2: potassium cyanide In dichloromethane; water at 10℃; for 2h; Large scale;	91%
dmap In acetonitrile at 84℃; for 10h; Conversion of starting material;

2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
With potassium cyanide; Aliquat 336 In water at 30℃; for 5h;	90%
With sodium cyanide; tetrabutylammomium bromide at 20 - 25℃; for 23h;	82%

sodium cyanide (773837-37-9) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
Stage #1: 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine With dmap In acetone for 5h; Reflux; Large scale; Stage #2: sodium cyanide In chloroform; water at 20℃; for 2.5h; Large scale;	89%
dmap In water; propiononitrile at 20℃; for 5h;	83%
With tetrabutylammomium bromide In water; dimethyl sulfoxide at 45 - 50℃; Concentration;	74.3%
With N-benzyl-N,N,N-triethylammonium chloride at 20℃; for 10h; Temperature;	46.7 g

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + lithium cyanide (788104-34-7, 25733-05-5) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
Stage #1: 2-bromo-3-chloro-5-(trifluoromethyl)pyridine With 4-pyrrolidin-1-ylpyridine In ethanol for 6h; Reflux; Large scale; Stage #2: lithium cyanide In water; 1,2-dichloro-ethane at 80℃; for 2h; Large scale;	88.1%

potassium cyanide + 1,2-dichloro-ethane (107-06-2) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → butanedinitrile (110-61-2) + 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
With dmap In water at 75 - 78℃; for 12h; Reagent/catalyst; Temperature;	A 81.8% B 86.7%

hydrogen cyanide (74-90-8) + 2,3-dichloro-5-trifluoromethylpyridine (69045-84-7) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
Stage #1: 2,3-dichloro-5-trifluoromethylpyridine With triethylamine In methanol for 4h; Reflux; Large scale; Stage #2: hydrogen cyanide In dichloromethane; water at 0℃; for 3h; Large scale;	85.7%

potassium cyanide (151-50-8) + 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine (72537-17-8) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
In dimethyl sulfoxide at 30℃; for 0.833333h;	84%

sodium cyanide (143-33-9) + 2,3-dichloro-5-trifluoromethylpyridine (69045-84-7) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
Stage #1: 2,3-dichloro-5-trifluoromethylpyridine With dmap In propiononitrile Heating / reflux; Stage #2: sodium cyanide In water; propiononitrile for 5h;	75.7%

sodium cyanide (773837-37-9) + 2,3-dichloro-5-trifluoromethylpyridine (69045-84-7) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
Stage #1: 2,3-dichloro-5-trifluoromethylpyridine; dmap In propiononitrile for 5h; Heating / reflux; Stage #2: sodium cyanide In water at 15℃; for 5h;	73%
dmap In 1,2-dimethoxyethane at 85℃; for 4h; Conversion of starting material;
dmap In acetonitrile at 82℃; for 21h; Conversion of starting material;
dmap In propiononitrile at 98℃; for 10.5h; Conversion of starting material;
In N,N-dimethyl-formamide at 120℃; for 8h;

tetra-n-butylammonium cyanide (10442-39-4) + 2,3-dichloro-5-trifluoromethylpyridine (69045-84-7) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
dmap In propiononitrile at 98℃; for 4h; Conversion of starting material;

2-bromo-3-chloro-5-(trifluoromethyl)pyridine (75806-84-7) + copper(l) cyanide + ammonium hydroxide → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
In N-methyl-acetamide; diethyl ether

3-chloro-5-(trifluoromethyl)picolinaldehydeoxime (246022-23-1) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
With Burgess Reagent In tetrahydrofuran at 65℃; for 1h;
With Burgess Reagent In tetrahydrofuran at 65℃; for 1h;

(3-chloro-5-trifluoromethyl-pyridin-2-yl)methylamine (175277-74-4) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
With ammonium hydroxide; oxygen In tert-Amyl alcohol at 110℃; under 2250.23 Torr; for 15h; Autoclave; Green chemistry;	92 %Chromat.

3-chloro-5-(trifluoromethyl)picolinaldehyde (175277-50-6) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; pyridine / ethanol / 1 h / 95 °C 2: Burgess Reagent / tetrahydrofuran / 1 h / 65 °C View Scheme
Multi-step reaction with 2 steps 1: pyridine; hydroxylamine hydrochloride / ethanol / 1 h / 95 °C 2: Burgess Reagent / tetrahydrofuran / 1 h / 65 °C View Scheme

2,3-dichloro-5-trifluoromethylpyridine (69045-84-7) → 3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium fluoride / dimethyl sulfoxide / 115 - 120 °C / Inert atmosphere 2: tetrabutylammomium bromide / dimethyl sulfoxide; water / 45 - 50 °C View Scheme

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) → 3-fluoro-5-(trifluoromethyl)picolinonitrile (80194-71-4)

Conditions	Yield
With potassium carbonate; cesium fluoride In dimethyl sulfoxide at 80 - 95℃; for 0.5h;	100%
With N-benzyl-N,N,N-triethylammonium chloride; sodium fluoride In N,N-dimethyl acetamide at 125 - 130℃; under 760.051 Torr; for 15h; Reagent/catalyst; Large scale;	95.2%
With potassium carbonate; dimethyl sulfoxide; cesium fluoride
With potassium carbonate; dimethyl sulfoxide; cesium fluoride
With potassium carbonate; dimethyl sulfoxide; cesium fluoride

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) → (3-chloro-5-trifluoromethyl-pyridin-2-yl)methylamine (175277-74-4)

Conditions	Yield
Stage #1: 3-chloro-2-cyano-5-(trifluoromethyl)pyridine With sodium hydroxide In methanol at 70℃; Stage #2: With sodium hypochlorite In methanol at 10℃; Solvent; Reagent/catalyst; Temperature;	98%
With sulfuric acid; 20% palladium hydroxide-activated charcoal; tetrabutylammomium bromide; hydrogen In methanol at 20℃; under 15001.5 Torr;	96.4%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) + acetic acid (64-19-7) → 1-[-3-chloro-5-(trifluoromethyl)pyridin-2-yl]methanamine acetate

Conditions	Yield
With hydrogen at 80℃; under 750.075 - 1500.15 Torr; for 15h; Temperature; Pressure; Autoclave;	97.8%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) → (3-chloro-5-trifluoromethyl-pyridin-2-yl)methylamine (175277-74-4) + 1-[5-(trifluoromethyl)pyridin-2-yl]methanamine (164341-39-3)

Conditions	Yield
With hydrogen; acetic acid; nickel at 40 - 45℃; under 13501.4 Torr; for 4h;	A 97% B 0.05%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) → 1-[5-(trifluoromethyl)-2-pyridinyl]methanamine hydrochloride (871826-12-9)

Conditions	Yield
With hydrogenchloride; 5% rhodium-on-charcoal; hydrogen In methanol; water at 100℃; under 7500.75 - 11251.1 Torr; for 10h; Catalytic behavior; Pressure; Autoclave;	96.5%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) + acetic acid (64-19-7) → 2-aminomethyl-5-trifluoromethylpyridine acetic acid

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In ethanol; water at 80℃; under 30003 - 33753.4 Torr; for 3h; Catalytic behavior; Pressure; Temperature; Autoclave;	96.4%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) → [3-chloro-5-(trifluoromethyl)-pyridin-2-yl]methanamine hydrochloride

Conditions	Yield
With hydrogenchloride; hydrogen; palladium on activated charcoal In methanol; water at 20℃; under 760.051 Torr; for 4h;	95%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) → 2-aminomethyl-5-trifluoromethylpyridine sulfate

Conditions	Yield
With sulfuric acid; 5% active carbon-supported ruthenium; hydrogen In water; isopropyl alcohol at 30℃; under 30003 - 33753.4 Torr; for 10h; Autoclave;	95%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) + ethyl 2-cyanoacetate (105-56-6) → ethyl 2-cyano-2-[2-cyano-5-(trifluoromethyl)-3-pyridyl]acetate

Conditions	Yield
Stage #1: ethyl 2-cyanoacetate With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: 3-chloro-2-cyano-5-(trifluoromethyl)pyridine In N,N-dimethyl-formamide at 70℃; for 2h;	91%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) + ethanol (64-17-5) → 3-chloro-5-trifluoromethylpyridine-2-carboxylic acid ethyl ester

Conditions	Yield
Stage #1: 3-chloro-2-cyano-5-(trifluoromethyl)pyridine; ethanol With pyridine; hydrogenchloride at 0 - 80℃; for 19h; Pinner Imino Ether Synthesis; Stage #2: In water at 25 - 30℃; for 2h; Concentration; Temperature;	87.6%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) + 2,4-difluorophenol (367-27-1) → 3-(2,4-difluorophenoxy)-5-trifluoromethylpyridine-2-carbonitrile

Conditions	Yield
Stage #1: 2,4-difluorophenol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.166667h; Inert atmosphere; Stage #2: 3-chloro-2-cyano-5-(trifluoromethyl)pyridine In N,N-dimethyl-formamide for 1h; Inert atmosphere;	71%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) + sodium phenoxide (139-02-6) → 3-phenoxy-5-(trifluoromethyl)picolinonitrile (1065607-70-6)

Conditions	Yield
In N,N-dimethyl-formamide at 80℃; for 1h;	67.5%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) + methylmagnesium bromide (75-16-1) → 1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethanone (207994-12-5)

Conditions	Yield
Stage #1: 3-chloro-2-cyano-5-(trifluoromethyl)pyridine; methylmagnesium bromide In tetrahydrofuran; toluene at -5 - 20℃; for 7h; Stage #2: With hydrogenchloride; water In tetrahydrofuran; toluene at 20℃; for 3h;	46%
Stage #1: 3-chloro-2-cyano-5-(trifluoromethyl)pyridine; methylmagnesium bromide In tetrahydrofuran; toluene at 0 - 20℃; for 7h; Stage #2: With hydrogenchloride In tetrahydrofuran; water; toluene at 20℃; for 3h;	40%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) → 1-[5-(trifluoromethyl)pyridin-2-yl]methanamine (164341-39-3)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In ethanol; water at 60℃; under 15001.5 - 18751.9 Torr; for 25h; Autoclave;	38%

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) → 3-chloro-5-trifluoromethylpyridine-2-carboxylic acid (80194-68-9)

Conditions	Yield
With sodium hydroxide In diethyl ether; ethanol; water

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) + 2-(tert-butoxycarbonylamino)phenylboronic acid (115377-94-1) → 2-(trifluoromethyl)benzo[f][1,7]naphthyridin-5-amine (1186635-27-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene at 100℃; Suzuki Coupling;
With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In water; toluene at 100℃;

3-chloro-2-cyano-5-(trifluoromethyl)pyridine (80194-70-3) + 2,4-difluorophenol (367-27-1) → 3-(2,4-difluorophenoxy)-5-trifluoromethylpyridine-2-carboxamide

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.17 h / 0 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sulfuric acid / 2 h / 50 °C / Inert atmosphere View Scheme

Upstream product

• 69045-84-7 2,3-dichloro-5-trifluoromethylpyridine 
• 151-50-8 potassium cyanide 
• 72537-17-8 2-fluoro-3-chloro-5-(trifluoromethyl)pyridine 
• 107-06-2 1,2-dichloro-ethane 
• 75806-84-7 2-bromo-3-chloro-5-(trifluoromethyl)pyridine 
• 788104-34-7 lithium cyanide 
• 74-90-8 hydrogen cyanide 
• 175277-50-6 3-chloro-5-(trifluoromethyl)picolinaldehyde 
• 175277-74-4 (3-chloro-5-trifluoromethyl-pyridin-2-yl)methylamine 
• 246022-23-1 3-chloro-5-(trifluoromethyl)picolinaldehydeoxime 
• 143-33-9 sodium cyanide 
• 10442-39-4 tetra-n-butylammonium cyanide 
• 773837-37-9 sodium cyanide 

Downstream Products

• 175277-74-4 (3-chloro-5-trifluoromethyl-pyridin-2-yl)methylamine 
• 164341-39-3 (5-(trifluoromethyl)pyridin-2-yl)methanamine 
• 80194-71-4 3-fluoro-5-(trifluoromethyl)picolinonitrile 
• 80194-68-9 3-chloro-5-trifluoromethylpyridine-2-carboxylic acid 
• 1065607-70-6 3-phenoxy-5-(trifluoromethyl)picolinonitrile 
• 128073-16-5 3-chloro-5-trifluoromethylpyridine-2-carboxylic acid ethyl ester 
• 871826-12-9 1-[5-(trifluoromethyl)pyridin-2-yl]methanamine hydrochloride 
• 89402-28-8 3-Fluoro-5-(Trifluoromethyl)Picolinic Acid 
• 89402-29-9 2-bromo-3-fluoro-5-(trifluoromethyl)-pyridine 
• 1065604-33-2 1-(4-(2-(3-phenoxy-5-(trifluoromethyl)pyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone 
• 1065607-76-2 1-benzoyl-3-(3-phenoxy-5-(trifluoromethyl)pyridin-2-yl)thiourea 
• 1065607-78-4 1-(3-phenoxy-5-(trifluoromethyl)pyridin-2-yl)thiourea 
• 1065607-72-8 3-phenoxy-5-(trifluoromethyl)picolinamide 
• 1065607-74-0 3-phenoxy-5-(trifluoromethyl)pyridin-2-amine 

Relevant articles and documents

Combined preparation method of 2-cyano-3-chloro-5-trifluoromethylpyridine and succinonitrile

The invention discloses a combined preparation method of 2-cyano-3-chloro-5-trifluoromethylpyridine and succinonitrile, and belongs to the field of organic chemistry. The method comprises the following steps: taking 2-fluoro-3-chloro-5-trifluoromethylpyridine and dichloroethane as raw materials, reacting in a potassium cyanide/sodium solution under the action of a phase transfer catalyst to obtaina mixed solution of 2-cyano-3-chloro-5-trifluoromethylpyridine and succinonitrile, layering, washing with water, and rectifying to obtain the 2-cyano-3-chloro-5-trifluoromethylpyridine with the content of more than 99% and the succinonitrile with the content of more than 99.9%. According to the method, the yield is high, the wastewater treatment is simple, byproducts are fully utilized, the yieldof the 2-cyano-3-chloro-5-trifluoromethylpyridine can reach 93%, and the yield of the succinonitrile can reach 95%.

3 - chloro -5 - trifluoromethyl pyridine compounds and intermediates method (by machine translation)

The invention discloses a 3 - chloro -5 - trifluoromethyl pyridine compound and preparation method of the midbody. The invention of the formula 3 a compound represented by the preparation method, comprising the following steps: organic solvent and water in the mixed solvent, under the action of the phase transfer catalyst, shown as 2 shown with the metal cyanide compounds of the substitution reaction, carbonized 3 compound of formula; further comprises the following steps: in the solvent, under the effect of the fluorination reagent, shown as 1 shown in the fluorination reaction of the compound, prepared states like the type 2 compound of formula; and can also be further comprises the following steps: under the action of the hydrogen and ethanol, shown as 3 shown in the Pinner reaction compound, then hydrolyzing the ester reaction, carbonized 4 compounds are shown. The invention of 3 - chloro -5 - trifluoromethyl pyridine compound preparation method of low cost, high production safety, simple operation, high yield, it is suitable for industrial production. (by machine translation)

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