696-82-2

Basic information

• Product Name: 2,4,6-TRIFLUOROPYRIMIDINE
• Synonyms: 2,4,6-TRIFLUOROPYRIMIDINE;Pyrimidine, 2,4,6-trifluoro- (6CI,7CI,8CI,9CI);2,4,6-Trifluoropyrimidine,98%;2,4,6-Trifluoropyrimidine 98%;2,4,6-TRIFLUOROPYRIMIDE;PyriMidine,2,4,6-trifluoro-
• CAS NO: 696-82-2
• Molecular Formula: C₄HF₃N₂
• Molecular Weight: 134.06
• EINECS: 211-801-1
• Product Categories: PYRIMIDINE
• Mol File: 696-82-2.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 83 °C
• Flash Point: >100°C
• Appearance: /
• Density: 1.514 g/cm³
• Vapor Pressure: 0.584mmHg at 25°C
• Refractive Index: 1.405
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -7.88±0.30(Predicted)
• Sensitive: Moisture Sensitive
• BRN: 607190
• CAS DataBase Reference: 2,4,6-TRIFLUOROPYRIMIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 2,4,6-TRIFLUOROPYRIMIDINE(696-82-2)
• EPA Substance Registry System: 2,4,6-TRIFLUOROPYRIMIDINE(696-82-2)

Safety Data

• Hazard Codes: C,Xi
• Statements: 34-37
• Safety Statements: 26-36/37/39-45
• RIDADR: 3265
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 696-82-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2,4,6-Trifluoropyrimidine is used as a key intermediate in the synthesis of various pharmaceuticals. Its fluorine-containing structure contributes to the enhancement of drug properties, such as bioavailability, metabolic stability, and target binding affinity.
Used in Agrochemical Industry:
In the agrochemical sector, 2,4,6-Trifluoropyrimidine is utilized as a precursor for the development of new pesticides and herbicides. Its incorporation into these compounds can improve their effectiveness and selectivity in controlling pests and weeds.
Used in Organic Synthesis:
2,4,6-Trifluoropyrimidine is employed as a versatile building block in organic synthesis for the creation of a wide range of fluorine-containing compounds. Its reactivity and stability make it suitable for various chemical reactions, leading to the formation of novel molecules with potential applications in different fields.
Used in Drug Discovery:
2,4,6-TRIFLUOROPYRIMIDINE is used as a starting material in drug discovery processes, where its unique structural features can be exploited to design and develop new therapeutic agents with improved pharmacological properties.
Used in Materials Science:
2,4,6-Trifluoropyrimidine's properties also make it a candidate for the development of new materials with specific characteristics, such as high thermal stability, chemical resistance, or specialized electronic properties, for use in various industries.

InChI:InChI=1/C4HF3N2/c5-2-1-3(6)9-4(7)8-2/h1H

Synthetic route

2,4,6-trichloropyrimidine (3764-01-0) → 2,4,6-trifluoropyrimidine (696-82-2)

Conditions	Yield
With 1,8-bis(dimethylamino)naphthalene (hydrogen fluoride) In acetonitrile Ambient temperature;	79%
With potassium fluoride; 18-crown-6 ether In sulfolane at 150℃; for 3.5h;	56%
With tetrabutyl phosphonium hydrogen difluoride at 50℃; for 4h;	85 % Chromat.

2,4,6-trichloropyrimidine (3764-01-0) → 2,4-dichloro-6-fluoropyrimidine (3833-57-6) + 2-fluoro-4,6-dichloropyrimidine (3824-45-1) + 2,4,6-trifluoropyrimidine (696-82-2)

Conditions	Yield
With potassium fluoride at 300℃; for 2h; Product distribution; C4HCl3N2/KF = 4 x 10 E-2, other times, other temperatures, other molar ratios, other fluorinated products;	A n/a B n/a C 37%

morpholine (110-91-8) + 2,4,6-trifluoropyrimidine (696-82-2) → 2,4-bis(morpholino)-6-fluoropyrimidine

Conditions	Yield
In N,N-dimethyl-formamide at 50 - 60℃; for 1h;	95%

2-methylpropylmagnesium chloride (5674-02-2) + 2,4,6-trifluoropyrimidine (696-82-2) → 2,4-difluoro-6-(2-methylpropyl)pyrimidine (1246034-33-2)

Conditions	Yield
iron(III)-acetylacetonate In tetrahydrofuran at -75 - -65℃; for 1.75h; Inert atmosphere;	94%

piperidine (110-89-4) + 2,4,6-trifluoropyrimidine (696-82-2) → 4-Fluoro-2,6-di-piperidin-1-yl-pyrimidine

Conditions	Yield
In N,N-dimethyl-formamide at 50 - 60℃; for 1h;	90%

hexamethylene imine (111-49-9) + 2,4,6-trifluoropyrimidine (696-82-2) → 2,4-bis(azepan-1-yl)-6-fluoropyrimidine

Conditions	Yield
In N,N-dimethyl-formamide at 50 - 60℃; for 1h;	90%

2,4,6-trifluoropyrimidine (696-82-2) + benzylamine (100-46-9) → N2,N4-Dibenzyl-6-fluoro-pyrimidine-2,4-diamine

Conditions	Yield
In N,N-dimethyl-formamide at 50 - 60℃; for 1h;	90%

ethylamine (75-04-7) + 2,4,6-trifluoropyrimidine (696-82-2) → N2,N4-Diethyl-6-fluoro-pyrimidine-2,4-diamine

Conditions	Yield
In water; N,N-dimethyl-formamide at 50 - 60℃; for 1h;	90%

phenylglyoxylic acid ethyl ester (1603-79-8) + tert-butyldimethylsilyloxydiethyl phosphonic ester (120341-31-3) + 2,4,6-trifluoropyrimidine (696-82-2) → ethyl 2-(diethoxyphosphoryloxy)-2-(2,6-difluoropyrimidin-4-yl)-2-phenylacetate

Conditions	Yield
With 1-tert-butyl-2,2,4,4,4-pentakis(dimethylamino)-2Λ5,4Λ5-catenadi(phosphazene) In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 4h; Inert atmosphere;	90%

dibutylamine (111-92-2) + 2,4,6-trifluoropyrimidine (696-82-2) → N2,N2,N4,N4-Tetrabutyl-6-fluoro-pyrimidine-2,4-diamine

Conditions	Yield
In N,N-dimethyl-formamide at 50 - 60℃; for 1h;	85%

N-butylamine (109-73-9) + 2,4,6-trifluoropyrimidine (696-82-2) → N2,N4-Dibutyl-6-fluoro-pyrimidine-2,4-diamine

Conditions	Yield
In N,N-dimethyl-formamide at 50 - 60℃; for 1h;	85%

piperazine (110-85-0) + 2,4,6-trifluoropyrimidine (696-82-2) → 4-Fluoro-2,6-di-piperazin-1-yl-pyrimidine

Conditions	Yield
In N,N-dimethyl-formamide at 50 - 60℃; for 1h;	80%

2,4,6-trifluoropyrimidine (696-82-2) + benzylmagnesium chloride (6921-34-2) → 2,4-difluoro-6-(phenylmethyl)pyrimidine (1246033-77-1)

Conditions	Yield
In tetrahydrofuran at -75 - -65℃; for 1.5h; Inert atmosphere;	79%

guanidine hydrochloride (50-01-1) + 2,4,6-trifluoropyrimidine (696-82-2) → 2-guanidino-4,6-difluoropyrimidine

Conditions	Yield
With sodium hydroxide In water at 0 - 10℃;	76%

4-[4-((S)-1-aminoethyl)benzyl]piperazine-1-carboxylic acid tert-butyl ester + 2,4,6-trifluoropyrimidine (696-82-2) → tert-butyl (S)-4-(4-(1-((4,6-difluoropyrimidin-2-yl)amino)ethyl)benzyl)piperazine-1-carboxylate

Conditions	Yield
In diethyl ether at -20 - 20℃;	74%

tert-butyl 4-[1-[4-[(1S)-1-aminoethyl]phenyl]-2-cyclopropylethyl]piperazine-1-carboxylate + 2,4,6-trifluoropyrimidine (696-82-2) → tert-butyl 4-(2-cyclopropyl-1-(4-((S)-1-((4,6-difluoropyrimidin-2-yl)amino)ethyl)phenyl)ethyl)piperazine-1-carboxylate

Conditions	Yield
In diethyl ether at -40 - 20℃;	74%

bis(1,5-cyclooctadiene)nickel (0) (1295-35-8) + 2,4,6-trifluoropyrimidine (696-82-2) + triethylphosphine (554-70-1) → [NiF(P(C2H5)3)2(C4HN2F2)] (256234-36-3)

Conditions	Yield
In hexane addn. of PEt3 to the Ni complex in hexane, stirring (room temp., 5 min),addn. of the pyrimidine, stirring (10 min); removal of volatiles (vac.), dissoln. (hexane), filtration, concn., crystn. on cooling tp -20°C overnight;	72%

1-Adamantanamine (768-94-5) + 2,4,6-trifluoropyrimidine (696-82-2) → Adamantan-1-yl-(2,6-difluoro-pyrimidin-4-yl)-amine + Adamantan-1-yl-(4,6-difluoro-pyrimidin-2-yl)-amine

Conditions	Yield
With sodium carbonate In water at 0 - 10℃; for 1h; Yields of byproduct given;	A n/a B 70%
With sodium carbonate In water at 0 - 10℃; for 1h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

ethylamine (75-04-7) + 2,4,6-trifluoropyrimidine (696-82-2) → 2-ethylamino-4,6-difluoropyrimidine (165258-59-3) + 4-ethylamino-2,6-difluoropyrimidine

Conditions	Yield
In water at 0 - 10℃; for 1h;	A 70% B 30%

2,4,6-trifluoropyrimidine (696-82-2) → 4-amino-2,6-difluoropyrimidine (675-12-7) + 2-amino-4,6-difluoropyrimidine (675-11-6) + 2,4-diamino-6-fluoropyrimidine (696-83-3)

Conditions	Yield
With ammonia In methanol at 20℃;	A n/a B n/a C 67%

[Ni(FHF)(P(C2H5)3)2(C4HN2F2)] + 2,4,6-trifluoropyrimidine (696-82-2) → [Ni(P(C2H5)3)2(C4HN2F2)(C4HN2F2O)] (256234-43-2)

Conditions	Yield
With CsOH*H2O In tetrahydrofuran stirring (room temp., 20 h); removal of volatiles (vac.), extn. (hexane), filtration, pptn. on concn.in vacuo;	67%

piperidine (110-89-4) + 2,4,6-trifluoropyrimidine (696-82-2) → 4,6-Difluoro-2-piperidin-1-yl-pyrimidine + 2,4-Difluoro-6-piperidin-1-yl-pyrimidine

Conditions	Yield
In water at 0 - 10℃; for 1h; Yields of byproduct given;	A 65% B n/a
In water at 0 - 10℃; for 1h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

2,4,6-trifluoropyrimidine (696-82-2) + benzylamine (100-46-9) → 2-benzylamino-4,6-difluoropyrimidine (130866-84-1) + 4-benzylamino-2,6-difluoropyrimidine

Conditions	Yield
In water at 0 - 10℃; for 1h; Yields of byproduct given;	A 65% B n/a
In water at 0 - 10℃; for 1h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

ethanolamine (141-43-5) + 2,4,6-trifluoropyrimidine (696-82-2) → 4,6-difluoro-(2-hydroxyethylamino)pyrimidine + 2-(2,6-difluoro-pyrimidin-4-ylamino)-ethanol

Conditions	Yield
In ethanol at 20℃;	A 65% B n/a

helium + 2,4,6-trifluoropyrimidine (696-82-2) → 2,4,5,6-tetrafluoropyrimidine (767-79-3)

Conditions	Yield
With fluorine; sodium fluoride In trichlorofluoromethane	64%

D-Alanine (338-69-2) + 2,4,6-trifluoropyrimidine (696-82-2) → N-(4,6-Difluoro-2-pyrimidyl)-D-α-alanine + N-(2,6-Difluoro-4-pyrimidyl)-D-α-alanine

Conditions	Yield
With sodium carbonate In water at 50℃; for 2h;	A 63% B 32%

2,4,6-trifluoropyrimidine (696-82-2) + glycine (56-40-6) → N-(2,6-Difluoro-4-pyrimidyl)glycine + N-(4,6-Difluoro-2-pyrimidyl)glycine (205817-03-4)

Conditions	Yield
With sodium carbonate In water at 50℃; for 2h;	A 28% B 62%

2,4,6-trifluoropyrimidine (696-82-2) + 3-amino propanoic acid (107-95-9) → N-(2,6-Difluoro-4-pyrimidyl)-β-alanine + N-(4,6-Difluoro-2-pyrimidyl)-β-alanine

Conditions	Yield
With sodium carbonate In water at 50℃; for 2h;	A 30% B 61%

morpholine (110-91-8) + 2,4,6-trifluoropyrimidine (696-82-2) → 4-morpholino-2,6-difluoropyrimidine + 2-morpholino-4,6-difluoropyrimidine

Conditions	Yield
In water at 0 - 10℃; for 1h; Yields of byproduct given;	A n/a B 60%
In water at 0 - 10℃; for 1h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

2,4,6-trifluoropyrimidine (696-82-2) + 4-amino-n-butyric acid (56-12-2) → N-(2,6-Difluoro-4-pyrimidyl)-γ-aminobutyric acid + N-(4,6-Difluoro-2-pyrimidyl)-γ-aminobutyric acid

Conditions	Yield
With sodium carbonate In water at 50℃; for 2h;	A 38% B 60%

2-(N,N-dimethylamino)ethanol (108-01-0) + 2,4,6-trifluoropyrimidine (696-82-2) → 2-((4,6-difluoropyrimidin-2-yl)oxy)-N,N-dimethylethanamine + 2-((2,6-difluoropyrimidin-4-yl)oxy)-N,N-dimethylethanamine

Conditions	Yield
In tetrahydrofuran at -78 - 20℃; for 1h;	A 55% B 5%

Upstream product

• 3764-01-0 2,4,6-trichloropyrimidine 

Downstream Products

• 696-83-3 2,4-diamino-6-fluoropyrimidine 
• 1429182-33-1 (S)-4,6-difluoro-N-(1-phenylethyl)pyrimidin-2-amine 
• 1631051-46-1 C₂₃H₁₉F₂N₃O₃ 
• 1246033-77-1 2,4-difluoro-6-(phenylmethyl)pyrimidine 
• 214897-29-7 C₁₀H₈F₂N₄O₃S 
• 252291-80-8 C₁₀H₈F₂N₄O₃S 
• 869676-57-3 [(PdMe)2(μ-κ2(P,P)Cy2PCH2PCy2)2(μ-F)][SiMeF4 
• 767-79-3 2,4,5,6-tetrafluoropyrimidine 
• 27078-75-7 4.6-Difluoro-2-methoxypyrimidin 
• 27078-76-8 2,4-difluoro-6-methoxy-pyrimidine 

Relevant articles and documents

Arylation of halogenated pyrimidines via a suzuki coupling reaction

The Suzuki coupling reaction has been used extensively for the synthesis of a wide variety of unsymmetrical biaryl compounds. We have extended this reaction to demonstrate the utility of preparing monophenyl-, diphenyl-, or triphenylpyrimidine depending on the reaction conditions. Further, it has been shown that chloropyrimidine substrates are preferable over iodo-, bromo-, or fluoropyrimidines.

Selective fluorination by halogen exchange of chlorodiazines and chloropyridines promoted by the 'proton sponge' - Triethylamine tris(hydrogen fluoride) system

The 'proton sponge' - triethylamine tris(hydrogen fluoride) mixtures provide a mild and efficient fluorinating reagent to introduce selectively fluorine atoms by halogen exchange into chlorodiazines and chloronitropyridine series.

Reactions involving fluoride ion. Part 37. "Proton Sponge" hydrofluoride as a fluoride ion donor

"Proton Sponge" hydrofluoride has been prepared and is totally soluble in acetonitrile; this system has been used to generate carbanions from hexafluoropropene and to form carbon-fluorine bonds by reaction with both 2,4,6-trichloropyrimidine and benzoyl chloride.

Proton Sponge Hydrofluoride as a Soluble Fluoride Ion Source

Proton Sponge (PS) hydrofluoride has been prepared and is totally soluble in acetonitrile; this system was used to generate carbanions from hexafluoropropene and to form carbon-fluorine bonds by reaction with 2,4,6-trichloropyrimidine and by reaction with benzoyl chloride (Proton Sponge hydrochloride is insoluble in acetonitrile).

NUCLEOPHILIC FLUORINATION OF CHLORINATED N-HETEROCYCLES WITH TETRABUTYLPHOSPHONIUM HYDROGENDIFLUORIDE AND DIHYDROGENTRIFLUORIDE

Fluorination of various chlorinated N-heterocycles with tetrabutylphosphonium hydrogendifluoride (1) or dihydrogentrifluoride (2) readilly proceeded in high yields under mild conditions.

LES FLUORATIONS COMPAREES DES CHLOROPYRIMIDINES ET DE LA CHLORO-S-TRIAZINE

The fluorinations of tetrachloropyrimidine, 2,4,6-trichloropyrimidine and trichloro-s-triazine were carried out in sealed tubes with KF in presence of inert gas and then compared.The fluorinated derivatives C4FxClyN2 with x + y = 4, O - were investigated and compared; the molar yields were found to be always higher than 50percent in our experimental conditions.We compare with the fluorinations of 2,4 and 4,6-dichloropyrimidine.It is possible to obtain directlyin good proportions, such fluorinated derivatives as 5-chlorotrifluoropyrimidine, trifluoropyrimidine and others.At high temperature (4OO deg C for 16h), tetrachloropyrimidine, in presence of KF, gave products of pyrolysis and condensation such as the fluorinated derivatives of C6Cl6 and C5Cl5N: C6FCl5, C6F2Cl4... or C5FCl4N, C5F2Cl3N...