13600-43-6

Basic information

• Product Name: 4-(Trifluoromethyl)nicotinonitrile
• Synonyms: BUTTPARK 43\57-45;3-CYANO-4-(TRIFLUOROMETHYL)PYRIDINE;4-TRIFLUOROMETHYL-3-PYRIDINENITRILE;4-(TRIFLUOROMETHYL)NICOTINONITRILE;3-Cyano-4-(trifluoromethyl)pyridine95+%;4-(trifluoroMethyl)pyridine-3-carbonitrile;3-Cyano-4-(trifluoromethyl)pyridine, 4-(Trifluoromethyl)pyridine-3-carbonitrile;4-(Trifluoromethyl)nicotinonitrile 95+%
• CAS NO: 13600-43-6
• Molecular Formula: C₇H₃F₃N₂
• Molecular Weight: 172.11
• Product Categories: Boron, Nitrile, Thio,& TM-Cpds;Heterocycles;Pyridines;Pyridine
• Mol File: 13600-43-6.mol

Chemical Properties

• Boiling Point: 75-77°C 15mm
• Flash Point: 97.1 °C
• Appearance: /
• Density: 1.37 g/cm³
• Vapor Pressure: 0.0452mmHg at 25°C
• Refractive Index: 1.456
• PKA: -0.57±0.18(Predicted)
• CAS DataBase Reference: 4-(Trifluoromethyl)nicotinonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(Trifluoromethyl)nicotinonitrile(13600-43-6)
• EPA Substance Registry System: 4-(Trifluoromethyl)nicotinonitrile(13600-43-6)

Safety Data

• Hazard Codes: Xi,Xn,T
• Statements: 36/37/38-20/21/22-25
• Safety Statements: 26-36-36/37-45
• HazardClass: IRRITANT
• Hazardous Substances Data: 13600-43-6(Hazardous Substances Data)

Usage

Chemical Properties

Pale yellow solid

InChI:InChI=1/C7H3F3N2/c8-7(9,10)5-1-2-12-6(3-5)4-11/h1-3H

Synthetic route

2,6-dichloro-4-(trifluoromethyl)pyridine-3-carbonitrile (13600-42-5) → 4-(trifluoromethyl)nicotinonitrile (13600-43-6)

Conditions	Yield
With pyridine; hydrogen In ethanol at 30℃; under 760.051 Torr; for 4h; Reagent/catalyst; Temperature; Solvent; Green chemistry;	98.5%
With palladium on activated carbon; hydrogen; triethylamine In tetrahydrofuran for 4h; Time;	95.22%

4-ethoxy-1,1,1-trifluoro-3-butene-2-one (59938-06-6, 17129-06-5) + (E/Z)-3-aminoprop-2-enenitrile (19866-98-9) → 4-(trifluoromethyl)nicotinonitrile (13600-43-6)

Conditions	Yield
Stage #1: 4-ethoxy-1,1,1-trifluoro-3-butene-2-one; (E/Z)-3-aminoprop-2-enenitrile In ethanol for 3h; Reflux; Sealed tube; Stage #2: With sodium ethanolate In ethanol for 5h; Reagent/catalyst; Solvent; Reflux; Sealed tube;	96.7%

(Z)-3-[(4,4,4-trifluoro-3-oxo-1-butenyl)amino]-2-propenenitrile (533932-97-7) + (E)-3-[(4,4,4-trifluoro-3-oxo-1-butenyl)amino]-2-propenenitrile (533932-96-6) → 4-(trifluoromethyl)nicotinonitrile (13600-43-6)

Conditions	Yield
With sodium methylate In methanol at 20℃; for 2h; Heating / reflux;	56.5%
With potassium carbonate In methanol for 2h; Heating / reflux;	32.7%

(Z)-3-[(4,4,4-trifluoro-3-oxo-1-butenyl)amino]-2-propenenitrile (533932-97-7) → 4-(trifluoromethyl)nicotinonitrile (13600-43-6)

Conditions	Yield
With sodium methylate In methanol at 20℃; for 2h; Heating / reflux;	47.2%

3-cyanopyridin-1-ium-1-yl tris(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)borate + (trifluoromethyl)trimethylsilane (81290-20-2) → 4-(trifluoromethyl)nicotinonitrile (13600-43-6) + 6-(trifluoromethyl)nicotinonitrile (216431-85-5)

Conditions	Yield
Stage #1: 3-cyanopyridin-1-ium-1-yl tris(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)borate; (trifluoromethyl)trimethylsilane With tetrabutylammonium triphenyldifluorosilicate In ethyl acetate at -40℃; for 11h; Molecular sieve; Inert atmosphere; Stage #2: With bis-[(trifluoroacetoxy)iodo]benzene In ethyl acetate at 25℃; for 10h; Inert atmosphere; regioselective reaction;	A 45% B 18%

(E)-3-[(4,4,4-trifluoro-3-oxo-1-butenyl)amino]-2-propenenitrile (533932-96-6) → 4-(trifluoromethyl)nicotinonitrile (13600-43-6)

Conditions	Yield
With sodium methylate In methanol at 20℃; for 2h; Heating / reflux;	41.5%

3-(4,4,4-trifluoro-3-oxo-1-butenyl)-2-propenenitrile → 4-(trifluoromethyl)nicotinonitrile (13600-43-6)

Conditions	Yield
With hydrogenchloride; Li2CO3 In methanol
With Li2CO3 In hydrogenchloride; methanol

(1,10-phenanthroline)(trifluoromethyl)copper (I) + 4-bromopyridine-3-carbonitrile (154237-70-4) → 4-(trifluoromethyl)nicotinonitrile (13600-43-6)

Conditions	Yield
In N,N-dimethyl-formamide at 80℃; for 8h; Sealed tube; Inert atmosphere;	92 %Spectr.

pyridine-3-carbonitrile (100-54-9) → 4-(trifluoromethyl)nicotinonitrile (13600-43-6) + 6-(trifluoromethyl)nicotinonitrile (216431-85-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: n-butyllithium / diethyl ether; hexane / 1 h / -78 °C / Inert atmosphere 1.2: -50 - 25 °C / Inert atmosphere 1.3: 12 h / 25 °C / Inert atmosphere 2.1: tetrabutylammonium triphenyldifluorosilicate / ethyl acetate / 11 h / -40 °C / Molecular sieve; Inert atmosphere 2.2: 10 h / 25 °C / Inert atmosphere View Scheme

2,6-dihydroxy-3-cyano-4-trifluoromethylpyridine N-methylmorpholine → 4-(trifluoromethyl)nicotinonitrile (13600-43-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: trichlorophosphate / 18 h / 130 °C / Inert atmosphere 2: triethylamine; hydrogen; palladium on activated carbon / tetrahydrofuran / 4 h View Scheme

4-(trifluoromethyl)nicotinonitrile (13600-43-6) → 4-(trifluoromethyl)nicotinic acid (158063-66-2)

Conditions	Yield
With water; sodium hydroxide at 100℃; Temperature;	98.3%
With sodium hydroxide In ethanol at 80℃; for 10h; Temperature; Inert atmosphere;	90.1%
Stage #1: 4-(trifluoromethyl)nicotinonitrile With potassium hydroxide; water In water; ethylene glycol at 200℃; for 4h; Stage #2: With hydrogenchloride In water; ethylene glycol at 20℃;	84%
With sulfuric acid In water at 110℃; for 12h;

4-(trifluoromethyl)nicotinonitrile (13600-43-6) → {[4-(trifluoromethyl)-3-pyridinyl]methyl}amine (771580-70-2)

Conditions	Yield
With ammonia; hydrogen; nickel In ethanol under 25858.1 Torr; for 1h;	98%

4-(trifluoromethyl)nicotinonitrile (13600-43-6) → 3-cyano-4-(trifluoromethyl)pyridine 1-oxide (287922-66-1)

Conditions	Yield
With dihydrogen peroxide; trifluoroacetic anhydride In dichloromethane; water at 0 - 40℃;	96%
With urea hydrogen peroxide adduct; trifluoroacetic anhydride In dichloromethane at 0 - 20℃; for 3h;	87%
With urea hydrogen peroxide adduct; trifluoroacetic anhydride In dichloromethane at 0 - 20℃; Inert atmosphere;	42%
With dihydrogen peroxide; trifluoroacetic acid In dichloromethane; water at 0 - 40℃; for 16h; Inert atmosphere;

4-(trifluoromethyl)nicotinonitrile (13600-43-6) → 4-(trifluoromethyl)-1,4,5,6-tetrahydropyridine-3-carbonitrile

Conditions	Yield
With C46H49CoN3P4(2+)*2BF4(1-); hydrogen; potassium hydroxide In isopropyl alcohol; acetonitrile at 100℃; under 22801.5 Torr; for 48h; Autoclave; Glovebox; chemoselective reaction;	89%

4-(trifluoromethyl)nicotinonitrile (13600-43-6) + trifluoroacetic acid (76-05-1) → {[4-(trifluoromethyl)-3-pyridinyl]methyl}amine bistrifluoroacetate

Conditions	Yield
Stage #1: 4-(trifluoromethyl)nicotinonitrile With ammonia; hydrogen; Raney-Ni In methanol for 16h; Stage #2: trifluoroacetic acid	47%

Upstream product

• 154237-70-4 4-bromopyridine-3-carbonitrile 
• 100-54-9 pyridine-3-carbonitrile 
• 59938-06-6 4-ethoxy-1,1,1-trifluoro-3-butene-2-one 
• 19866-98-9 (E/Z)-3-aminoprop-2-enenitrile 
• 120417-45-0 4-amino-1,1,1-trifluoro-3-butene-2-one 
• 13600-42-5 2,6-dichloro-4-(trifluoromethyl)pyridine-3-carbonitrile 
• 81290-20-2 (trifluoromethyl)trimethylsilane 
• 533932-97-7 (Z)-3-[(4,4,4-trifluoro-3-oxo-1-butenyl)amino]-2-propenenitrile 
• 533932-96-6 (E)-3-[(4,4,4-trifluoro-3-oxo-1-butenyl)amino]-2-propenenitrile 

Downstream Products

• 158063-66-2 4-(trifluoromethyl)nicotinic acid 
• 771580-70-2 {[4-(trifluoromethyl)-3-pyridinyl]methyl}amine 
• 198401-76-2 (4-(trifluoromethyl)pyridin-3-yl)methanol 
• 896447-72-6 2-chloro-4-(trifluoromethyl)nicotinonitrile 
• 175204-85-0 N'-hydroxy-4-(trifluoromethyl)pyridine-3-carboximidamide 

Relevant articles and documents

Preparation process 4 - trifluoromethyl nicotinic acid

The invention discloses a preparation process of 4 -trifluoromethyl nicotinic acid and vinyl ether. Trifluoracetyl chloride and catalyst were added to the reactor and stirred. Acylation to obtain 4 - ethoxy -1, 1, 1 -trifluoro -3 - alkene -2 - ketone, reacting 4 - with a catalyst and an oxidizing agent to -1 ethoxy 1, 1 -3 -trifluoro -2 -butenone, 25 - 90 °C g 30 - 60min of 1-trifluoroethyl 1-butenecone, adding 1 - equivalents of alkali lye, and then acidifying to obtain -4 - 2-trifluoromethylnicotiniconicotinic acid, followed by acidification with -3 - 4 -chloro 1 - 5-4 - trifluoromethyl POCl3 picolinic 6 - acid -4 . The preparation method of 4 -trifluoromethyl nicotinic acid is optimized. Only the reaction temperature is controlled, the intermediate product can be used for subsequent reaction steps, the reaction requirements in the step process are reduced, the requirement for equipment is low, and industrialization can be conveniently realized.

Method for preparing 3-cyano-4-trifluoromethylpyridine by using Ni-Fe/C bimetallic supported catalyst

The invention belongs to the technical field of preparation of flonicamid, and particularly relates to a method for preparing 3-cyan-4-trifluoromethylpyridine by using a Ni-Fe/C bimetallic supported catalyst. The method comprises the following steps: by taking 2,6-dichloro-3-cyano-4-trifluoromethylpyridine as a raw material, carrying out normal-pressure hydrogenation by using a Ni-Fe/C bimetallicsupported catalyst to obtain a crude product 3-cyano-4-trifluoromethylpyridine, and purifying to obtain the high-purity 3-cyano-4-trifluoromethylpyridine. Compared with a conventional dechlorination hydrogenation catalyst, the Ni/Fe bimetallic loaded catalyst has the advantages of stable activity, recyclability, low cost, high selectivity in the dechlorination process and high yield.

Method for preparing 4-(trifluoromethyl)nicotinic acid

The invention discloses a method for preparing 4-(trifluoromethyl)nicotinic acid, and belongs to the technical field of methods for preparing chemical pharmaceutical intermediates. The method comprises steps of using trifluoroacetyl chloride, vinyl ethyl ether and 3-aminoacrylonitrile as raw materials to prepare the 4-(trifluoromethyl)nicotinic acid through acylation, cyclization and hydrolysis reactions. The method provided by the invention is relatively cheap and easily available in adopted raw material, simple and convenient to operate, easy in separation and purification of products in each step, high in yield, and more suitable for industrial production.

Preparation methods of flonicamid and intermediate 4-(trifluoromethyl)nicotinic acid thereof

The invention relates to preparation methods of flonicamid and an intermediate 4-(trifluoromethyl)nicotinic acid thereof. The preparation method of 4-(trifluoromethyl)nicotinic acid comprises the steps that cyanoacetamide, ethyl 4,4,4-trifluoroacetoacetate and organic alkali serve as the raw materials, 2,6-dyhydroxy-3-cyano-4-tirfluoromethylpyridine N-methylmorpholine salt is prepared first, and then phosphorus oxychloride chlorination, catalytic hydrogenation and hydrolyzation are conducted in sequence to obtain 4-(trifluoromethyl)nicotinic acid; the preparation method of the flonicamid comprises the steps that 4-(trifluoromethyl)nicotinic acid is prepared and then mixed with glycinonitrile hydrochloride, and after an amidation reaction is conducted, the flonicamid is obtained. Compared with the prior art, the total recovery of the prepared flonicamid is high, the cost is low, operation is easy, the equipment requirement is low, and the requirement of industrial production can be met;the technological process is simple, separation and purification are easy, and the reaction condition is mild.

4-Position-Selective C-H Perfluoroalkylation and Perfluoroarylation of Six-Membered Heteroaromatic Compounds

The first 4-position-selective C-H perfluoroalkylation and perfluoroarylation of six-membered heteroaromatic compounds were achieved using nucleophilic perfluoroalkylation and perfluoroarylation reagents. The regioselectivity was controlled by electrophilically activating the heteroaromatic rings, while sterically hindering the 2-position, with a sterically bulky borane Lewis acid. The reaction proceeded in good yield, even in gram scale, and by a sequential reaction without isolating the intermediates. This reaction could be applied to late-stage trifluoromethylation of a bioactive compound.

Copper-mediated perfluoroalkylation of heteroaryl bromides with (phen)CuRF

The attachment of perfluoroalkyl groups onto organic compounds has been a major synthetic goal over the past several decades. Previously, our group reported phenanthroline-ligated perfluoroalkyl copper reagents, (phen)CuR F, which react with aryl iodides and aryl boronates to form the corresponding benzotrifluorides. Herein the perfluoroalkylation of a series of heteroaryl bromides with (phen)CuCF3 and (phen)CuCF 2CF3 is reported. The mild reaction conditions allow the process to tolerate many common functional groups. Perfluoroethylation with (phen)CuCF2CF3 occurs in somewhat higher yields than trifluoromethylation with (phen)CuCF3, creating a method to generate fluoroalkyl heteroarenes that are less accessible from trifluoroacetic acid derivatives.

N-HETEROARYLNICOTINAMIDE DERIVATIVES

An N-heteroaryl-4-(haloalkyl)nicotinamide derivative represented by formula (I): [wherein R represents a C1-C6 haloalkyl group; R1 represents a hydrogen atom, a C1-C6 alkyl group which may be substituted a C2-C6 alkenyl group or an acyl group; X represents a group represented by formula C-R2, or a nitrogen atom; R2 and R3 each independently represent a hydrogen atom, a halogen atom, a C1-C6 alkyl group which may be substituted, a C3-C7 cycloalkyl group, a C2-C6 alkenyl group, a C3-C7 cycloalkenyl group, a formyl group, a group represented by formula CH=NOR4, a cyano group, a phenyl group which may be substituted, a heterocyclic group which may be substituted, a C1-C6 alkoxy group which may be substituted, a C1-C6 alkylthio group or a phenoxy group]; or a salt thereof, a pesticide containing it as an active component, a method for producing it and intermediates thereof.

Process for the preparation of 4-Haloalkylnicotinonitriles

4-Haloalkylnicotinonitriles having the formula (I) which are suitable as intermediates in the preparation of pesticides, are obtained by: (a) reacting a 3-amino-1-haloalkyl-2-propen-1-one RF—C(O)—CH═CH—NH2??(II) in a condensation reaction with a compound of the formula (III) to (VII), (R1Z)CH═CH—CN??(III) (R1Z)2CH—CH2—CN??(IV) Hal—CH═CH—CN??(V) Hal2CH—CH2CN??(VI) HC≡C—CN??(VII), to give a compound of the formula (VIII), (IX) and/or (X), RF—C(O)—CH═CH—NH—CH═CH—CN??(VIII) RF—C(O)—CH═CH—NH—CH(ZR1)—CH2—CN??(IX) RF—C(O)—CH═CH—NH—CH(Hal)—CH2—CN??(X), wherein RF is (C1-C4)-haloalkyl, R1 is alkyl, Hal is Cl or Br and each Z, independently, is O, S, NR1 or OCO; and (b) subjecting the reaction product to a ring closure reaction.