697-83-6

Basic information

• Product Name: 5-Chloro-2,4,6-trifluoropyrimidine
• Synonyms: 5-CHLORO-2,4,6-TRIFLUOROPYRIMIDINE;AKOS BBS-00006250;5-Chloro-2,4,6-Trifluoropyrimide;2,4,6-TRIFLUORO-5-CHLOROPYRIMIDINE;5-CHLORO-2,4,6-TRIFLUORO-PYRIMIDIN;Pyrimidine, 5-chloro-2,4,6-trifluoro-;5-Chloro-2,4,6-trifluoropyrimidine,97%
• CAS NO: 697-83-6
• Molecular Formula: C₄ClF₃N₂
• Molecular Weight: 168.5
• EINECS: 211-807-4
• Product Categories: Pyrimidine;Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Pyrimidines;PyrimidinesHeterocyclic Building Blocks;Building Blocks;C4 to C5;Chemical Synthesis;Fluorinated Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Heterocyclic Fluorinated Building Blocks;Other Fluorinated Heterocycles
• Mol File: 697-83-6.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 116 °C(lit.)
• Flash Point: >230 °F
• Appearance: Clear colorless/Liquid
• Density: 1.626 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.501mmHg at 25°C
• Refractive Index: n20/D 1.439(lit.)
• BRN: 610168
• CAS DataBase Reference: 5-Chloro-2,4,6-trifluoropyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Chloro-2,4,6-trifluoropyrimidine(697-83-6)
• EPA Substance Registry System: 5-Chloro-2,4,6-trifluoropyrimidine(697-83-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39
• WGK Germany: 3
• HazardClass: IRRITANT, MOISTURE SENSITIVE
• Hazardous Substances Data: 697-83-6(Hazardous Substances Data)

Usage

Chemical Properties

clear colorless liquid

Uses

5-Chloro-2,4,6-trifluoropyrimidine can be used as a starting material to synthesize: 4-azido-5-chloro-2,6-difluoro-pyrimidine by azidation reaction with sodium azide. 5-chloro triphenoxy pyrimidine by reacting with tetraphenoxysilane in the presence of tetra butyl ammonium fluoride (TBAF). 5-chloro-2,6-difluoropyrimidin-4-amine, and 5-chloro-4,6-difluoropyrimidin-2-amine (9:1 ratio) by reacting with ammonia. 5-Chloro-N,N -diethyl-2,6-dipyrimidin-4-amine, by treating with diethylamine and DIPEA.

InChI:InChI=1/C5HCl2F2N/c6-2-1-3(7)5(9)10-4(2)8/h1H

Synthetic route

2,4,5,6-tetrachloropyrimidine (1780-40-1) → 2,4,6-trifluoro-5-chloropyrimidine (697-83-6)

Conditions	Yield
With potassium fluoride; 18-crown-6 ether In sulfolane at 190℃; for 15h;	91%

2,4,6-trifluoropyrimidine (696-82-2) → 2,4,5,6-tetrafluoropyrimidine (767-79-3) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6)

Conditions	Yield
With chlorine pentafluoride In various solvent(s) at 0℃;	A 14.8% B 8.7%

2,4,5,6-tetrafluoropyrimidine (767-79-3) → 2,4,6-trifluoro-5-chloropyrimidine (697-83-6)

2,3,4,6-Tetra-O-benzyl-D-glucopyranose (4291-69-4, 6386-24-9, 6564-72-3, 59531-24-7, 69257-52-9, 78184-89-1, 78609-16-2, 78609-17-3, 78609-18-4, 96553-53-6, 104111-61-7, 131347-08-5, 4132-28-9) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 5-chloro-2,6-difluoro-4-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyloxy)pyrimidine

Conditions	Yield
With 15-crown-5; sodium hydride In dichloromethane -40 deg C, 15 min, then room temp.;	85%

tetraphenoxysilane (1174-72-7) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 2,4,6-triphenoxy-5-chloropyrimidine

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran; acetone at 50℃; for 16h;	85%

tetramethylorthosilicate (681-84-5) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 5-chloro-2,4,6-trimethoxy-pyrimidine (4319-89-5)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran; acetone at 50℃; for 24h;	81%

2,3,4,5-tetra-O-acetyl-D-glucopyranose (3947-62-4, 6207-76-7, 19235-21-3, 22554-70-7, 22860-22-6, 47339-09-3, 57884-82-9, 62057-79-8, 70191-05-8, 109525-54-4, 140147-37-1, 10343-06-3) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 5-chloro-2,6-difluoro-4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)pyrimidine

Conditions	Yield
With 15-crown-5; sodium hydride In dichloromethane -20 deg C, 15 min, then room temp.;	80%

tetraallyloxysilane (1067-43-2) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → C13H15ClN2O3

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran; acetone at 50℃; for 24h;	79%

tetraethoxy orthosilicate (78-10-4) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 5-chloro-2,4,6-triethoxy-pyrimidine (4319-91-9)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran; acetone at 50℃; for 24h;	75%

tetrakis(triphenylphosphine) palladium(0) (14221-01-3) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → trans-[PdCl(5-C4N2F3)(PPh3)2] (863225-16-5)

Conditions	Yield
In toluene soln. of Pd complex in toluene treated with ligand (1 equiv.); heated toreflux for 2 h; cooled to room temp.; filtered; volatiles removed from filtrate under vac.; washed with hexane; dried in vac.; elem. anal.;	73%

2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 4-azido-5-chloro-2,6-difluoropyrimidine (76411-48-8) + 4,6-diazido-5-chloro-2-fluoropyrimidine

Conditions	Yield
With sodium azide In acetonitrile 0 deg C, 6 h, RT, 30 min;	A 60% B 16%

2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 4,6-diamino-5-chloro-2-fluoropyrimidine (1353054-67-7) + 2,4-diamino-5-chloro-6-fluoropyrimidine (1353054-66-6)

Conditions	Yield
With ammonia In water; acetonitrile at 0 - 45℃; for 10h;	A 57% B 31%

bis(1,5-cyclooctadiene)nickel (0) (1295-35-8) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) + tris(1-methylethyl)phosphine (6476-36-4) → trans-[NiF(4-C4N2ClF2)(P-i-Pr3)2] (863225-13-2)

Conditions	Yield
In tetrahydrofuran suspn. of Ni complex in THF treated with phosphine (2 equiv.); 10 min; ligand (1 equiv.) added; stirred at room temp. for 2 h; volatiles removed under vac.; extd. with hexane; volatiles removed from extract in vac.; elem. anal.;	42%

bis(1,5-cyclooctadiene)nickel (0) (1295-35-8) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) + tricyclohexylphosphine (2622-14-2) → trans-[NiF(4-C4N2ClF2)(P(C6H11)3)2] (433725-49-6)

Conditions	Yield
In hexane Ni complex was treated sequantially with PCy3 and pyrimidine in hexane soln. at room temp.; NMR monitoring; recrystd. (hexane, -20°C); elem. anal.;	34%

bis(1,5-cyclooctadiene)nickel (0) (1295-35-8) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) + triphenylphosphine (603-35-0) → trans-[NiCl(4-C4N2ClF2)(PPh3)2] (863225-15-4) + trans-[NiF(4-C4N2ClF2)(PPh3)2] (863225-14-3)

Conditions	Yield
In tetrahydrofuran suspn. of Ni complex in THF treated with phosphine (2.3 equiv.); stirredat room temp. for 5 min; ligand (1 equiv.) added; stirred for 4 h; volatiles removed under vac.; washed with cold hexane; dried in vac.; elem. anal.;	A n/a B 31%

bis(1,5-cyclooctadiene)nickel (0) (1295-35-8) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) + triethylphosphine (554-70-1) → trans-[NiCl(5-C4N2F3)(PEt3)2] (433725-48-5)

Conditions	Yield
In hexane Ni complex was treated sequantially with PEt3 and pyrimidine in hexane soln. at room temp.; crystd. at -20°C; elem. anal.;	20%

2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 4-azido-5-chloro-2,6-difluoropyrimidine (76411-48-8)

Conditions	Yield
With sodium azide In acetonitrile

2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → Di-fluoro-mono-chloro-pyrimidine (25151-07-9)

Conditions	Yield
Stage #1: 2,4,6-trifluoro-5-chloropyrimidine With bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine In hexane at 20℃; for 2h; Stage #2: With hydrogenchloride In diethyl ether; benzene-d6 Further stages.;

2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 5-chloro-2,6-difluoro-4-iodopyrimidine

Conditions	Yield
Stage #1: 2,4,6-trifluoro-5-chloropyrimidine With bis(1,5-cyclooctadiene)nickel (0); tricyclohexylphosphine In hexane at 20℃; for 2h; Stage #2: With iodine In benzene-d6 Further stages.;

morpholine (110-91-8) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 4-(5-chloro-2,6-difluoropyrimidin-4-yl)morpholine (639855-32-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 20℃; for 16h;

cis-3,5-dimethylpiperidine + trans-3,5-dimethylpiperidine + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → 5-chloro-2,4-difluoro-6-(3,5-dimethylpiperidino)pyrimidine + 5-chloro-2,4-difluoro-6-(3,5-dimethylpiperidino)pyrimidine

Conditions	Yield
In tetrahydrofuran at 20℃; for 1.5h;

trimethyl-(3-aminophenyl)-ammonium chloride (6375-71-9) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → Azure B

Conditions	Yield
With sodium carbonate; sodium chloride In water

trimethyl-(4-aminophenyl)-ammonium chloride + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → Azure B

Conditions	Yield
With sodium carbonate In water

5-nitro-2-(β-sulphoethylamino)-benzenesulphonamide (107342-21-2) + Tau (107-35-7) + 2-chloro-5-nitrobenzenesulfonamide (96-72-0) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) + 4-chloro-2,5,6-trifluoropyrimidine (96819-50-0) → 5-amino-2-(β-sulphoethylamino)-benzenesulphonamide (107342-25-6)

Conditions	Yield
With sodium hydroxide; potassium chloride In aluminum nickel; water

(1S,4R)-7,7-dimethyl-1-({[(3R)-3-methyl-1-piperazinyl]sulfonyl}methyl)bicyclo[2.2.1]heptan-2-one (943238-10-6) + 2,4,6-trifluoro-5-chloropyrimidine (697-83-6) → (1S,4R)-1-({[(3R)-4-(5-chloro-2,6-difluoro-4-pyrirnidinyl)-3-methyl-1-piperazinyl]sulfonyl}methyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-one + (1S,4R)-1-({[(3R)-4-(5-chloro-4,6-difluoro-2-pyrirnidinyl)-3-methyl-1-piperazinyl]sulfonyl}methyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-one

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 50℃; for 16h;

Upstream product

• 696-82-2 2,4,6-trifluoropyrimidine 
• 767-79-3 2,4,5,6-tetrafluoropyrimidine 
• 1780-40-1 2,4,5,6-tetrachloropyrimidine 

Downstream Products

• 863225-15-4 trans-[NiCl(4-C₄N₂ClF₂)(PPh₃)2] 
• 863225-14-3 trans-[NiF(4-C₄N₂ClF₂)(PPh₃)2] 
• 863225-16-5 trans-[PdCl(5-C₄N₂F₃)(PPh₃)2] 
• 433725-49-6 trans-[NiF(4-C₄N₂ClF₂)(P(C₆H₁₁)3)2] 
• 107342-25-6 5-amino-2-(β-sulphoethylamino)-benzenesulphonamide 
• 25151-07-9 Di-fluoro-mono-chloro-pyrimidine 

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