77326-36-4

Basic information

• Product Name: 2-Amino-6-fluorobenzonitrile
• Synonyms: 2-FLUORO-6-AMINOBENZONITRILE;2-AMINO-6-FLUOROBENZONITRILE;6-FLUOROANTHRANILONITRILE;6-AMINO-2-FLUOROBENZONITRILE;2-Amino-6-fluorobenzonitrile, 97+% (6-Fluoroanthranilonitrile);Benzonitrile, 2-amino-6-fluoro- (9CI);2-Amino-6-fluorobenzonitrile 98%;2-Amino-6-fluorobenzonitrile98%
• CAS NO: 77326-36-4
• Molecular Formula: C₇H₅FN₂
• Molecular Weight: 136.13
• Product Categories: NITRILE;Aromatic Nitriles;Benzene series;Amines;Aromatics;Miscellaneous Reagents
• Mol File: 77326-36-4.mol
• Article Data: 10

Chemical Properties

• Melting Point: 125-128 °C(lit.)
• Boiling Point: 275.775 °C at 760 mmHg
• Flash Point: 120.585 °C
• Appearance: white to light yellow crystal powder
• Density: 1.256 g/cm³
• Vapor Pressure: 0.805mmHg at 25°C
• Refractive Index: 1.399
• Storage Temp.: Refrigerator
• Solubility: Chloroform
• PKA: 0.80±0.10(Predicted)
• BRN: 3588945
• CAS DataBase Reference: 2-Amino-6-fluorobenzonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Amino-6-fluorobenzonitrile(77326-36-4)
• EPA Substance Registry System: 2-Amino-6-fluorobenzonitrile(77326-36-4)

Safety Data

• Hazard Codes: Xi,T,Xn
• Statements: 36-36/37/38-20/21/22
• Safety Statements: 26-36-36/37/39-22
• RIDADR: 3439
• WGK Germany: 2
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 77326-36-4(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powder

Uses

2-Amino-6-fluorobenzonitrile, a medicinal chemistry intermediate, has been employed for the preparation of tacrine-related compounds. It may be used for the synthesis of antifolate and antibacterial quinazoline derivatives. It may be used for the synthesis bis(4-oxoquinazolin-2-yl)pyridine and fluoro-containing quinazolin-4(1H)-ones. It may be employed for the synthesis of the following novel huprines:12-amino-3-chloro-6,7,10,11-tetrahydro-9-isopropyl-7,11-methanocycloocta[b]quinoline hydrochloride9-allyl-12-amino-3-chloro-6,7,10,11-tetrahydro-7,11-methanocycloocta[b]quinoline hydrochloride12-amino-1-fluoro-6,7,10,11-tetrahydro-9-isopropyl-7,11-methanocycloocta[b]quinoline hydrochloride9-allyl-12-amino-1-fluoro-6,7,10,11-tetrahydro-7,11-methanocycloocta[b]quinoline hydrochloride

General Description

2-Amino-6-fluorobenzonitrile can be prepared by treatment of 2,6- difluorobenzonitrile with ammonia, which involves displacement of one of the activated fluorine atoms.

InChI:InChI=1/C9H18F3NOSi/c1-8(2,3)15(5,6)13(4)7(14)9(10,11)12/h1-6H3

Synthetic route

2,6 difluorobenzonitrile (1897-52-5) → 2-amino-6-fluorobenzonitrile (77326-36-4)

Conditions	Yield
With ammonia In dimethyl sulfoxide at 80℃; for 80h; closed bottle;	99%
With ammonia In ethanol at 140℃; under 10343.2 Torr; for 6h;	97%
With ammonia In dimethyl sulfoxide at 80 - 120℃;	97.5%

meta-fluoroaniline (372-19-0) + trichloroacetonitrile (545-06-2) → 2-amino-6-fluorobenzonitrile (77326-36-4)

Conditions	Yield
With boron trichloride; tin(IV) chloride; potassium carbonate 1.) CH2Cl2, reflux, 24 h, 2.) CH3OH, reflux, 2.5 h; Yield given. Multistep reaction;

2,6-dichloro-benzonitrile (1194-65-6) → 2-amino-6-fluorobenzonitrile (77326-36-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: KF; 18-crown-6 / 3 h / 180 °C 2: NH3 / 10 h / 100 °C View Scheme

NH4 OAc + 2,6 difluorobenzonitrile (1897-52-5) → 2-amino-6-fluorobenzonitrile (77326-36-4)

Conditions	Yield
In formamide

2-(aminomethyl)-3-fluoroaniline → 2-amino-6-fluorobenzonitrile (77326-36-4)

Conditions	Yield
With ammonium hydroxide; oxygen In tert-Amyl alcohol at 110℃; under 2250.23 Torr; for 24h; Autoclave; Green chemistry;	92 %Chromat.

2-amino-6-fluorobenzonitrile (77326-36-4) → 2-amino-6-fluorobenzamide (115643-59-9)

Conditions	Yield
With water; potassium carbonate at 150℃; for 0.25h; Microwave irradiation;	99%
With water; potassium carbonate at 150℃; for 0.5h; Microwave irradiation;	94%
With water; potassium carbonate In water at 150℃; for 0.5h; Microwave irradiation;	94%

2-amino-6-fluorobenzonitrile (77326-36-4) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → N’-(2-cyano-3-fluorophenyl)-N,N-dimethylformimidamide

Conditions	Yield
at 100℃; for 0.5h;	99%
In toluene at 120℃; for 1.5h;

2-amino-6-fluorobenzonitrile (77326-36-4) + 4-trifluoromethyl-phenyl acetyl chloride (329-15-7) → N-(2-cyano-3-fluorphenyl)-4-(trifluoromethyl)benzamide

Conditions	Yield
With pyridine at 20℃; for 16h; Inert atmosphere;	99%

2-amino-6-fluorobenzonitrile (77326-36-4) + chloroformic acid ethyl ester (541-41-3) → ethyl (2-cyano-3-fluorophenyl)carbamate

Conditions	Yield
at 100℃; for 18h;	99%

2-amino-6-fluorobenzonitrile (77326-36-4) → 2-amino-6-fluorobenzothioamide

Conditions	Yield
With sodium hydrogen sulfide monohydrate; magnesium chloride In N,N-dimethyl-formamide at 20℃; for 72h; Sealed tube;	97%

2-amino-6-fluorobenzonitrile (77326-36-4) → 6-amino-3-bromo-2-fluorobenzonitrile (845866-92-4)

Conditions	Yield
With N-Bromosuccinimide; acetic acid at 30℃; for 18h; Temperature;	95.3%

2-amino-6-fluorobenzonitrile (77326-36-4) + phenyl isothiocyanate (103-72-0) → 4-anilino-5-fluoroquinazoline-2-thiol (1098337-03-1)

Conditions	Yield
at 100℃; for 3.5h;	95%

2-amino-6-fluorobenzonitrile (77326-36-4) + phenyl isothiocyanate (103-72-0) → 2,2'-dithiobis(5-fluoro-4-phenylaminoquinazoline)

Conditions	Yield
at 100℃; for 3.5h;	95%

piperazine (110-85-0) + 2-amino-6-fluorobenzonitrile (77326-36-4) → 2-amino-6-(piperazin-1-yl)benzonitrile

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 160℃; for 5h;	95%

2-amino-6-fluorobenzonitrile (77326-36-4) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 5-fluoro-1H-quinazoline-2,4(1H,3H)-dione (192570-33-5)

Conditions	Yield
With carbon dioxide In water at 150℃; under 37503.8 Torr; for 5h;	94.8%

bromobenzene (108-86-1) + 2-amino-6-fluorobenzonitrile (77326-36-4) + molybdenum hexacarbonyl (13939-06-5, 199620-15-0) → N-(2-cyano-3-fluorophenyl)benzonitrile (606145-77-1)

Conditions	Yield
With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In N,N-dimethyl-formamide at 130℃; for 16h; Inert atmosphere; Sealed tube;	92%

2-amino-6-fluorobenzonitrile (77326-36-4) → 2,2'-(triazene-1,3-diyl)-bis(6-fluorobenzonitrile) (1600526-88-2)

Conditions	Yield
With hydrogenchloride; sodium nitrite In water at 0 - 20℃; for 20h;	92%

methanol (67-56-1) + 2-amino-6-fluorobenzonitrile (77326-36-4) → 2-amino-6-fluoro-benzoic acid,methyl ester (86505-94-4)

Conditions	Yield
With hydrogenchloride Pinner reaction;	91%

2-amino-6-fluorobenzonitrile (77326-36-4) + 3-fluorobenzoyl chloride (1711-07-5) → N-(2-cyano-3-fluorophenyl)-3-fluorobenzamide (1153761-87-5)

Conditions	Yield
With pyridine In tetrahydrofuran at 0 - 20℃; for 3h;	91%

2-amino-6-fluorobenzonitrile (77326-36-4) + 3-Fluorobenzaldehyde (456-48-4) → 2-fluoro-6-(3-fluorobenzylamino)benzonitrile (1153511-93-3)

Conditions	Yield
Stage #1: 2-amino-6-fluorobenzonitrile; 3-Fluorobenzaldehyde With trifluoroacetic acid In acetic acid at 35 - 40℃; for 1.5h; Large scale reaction; Stage #2: With sodium tris(acetoxy)borohydride In acetic acid at 40℃; for 1h;	90.3%

2-amino-6-fluorobenzonitrile (77326-36-4) → 2-amino-6-fluorobenzoic acid (434-76-4)

Conditions	Yield
With sodium hydroxide In water for 12h; Heating;	90%
With sodium hydroxide In ethanol
With sodium hydroxide In ethanol; water

[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]acetic acid ethyl ester (402948-37-2) + 2-amino-6-fluorobenzonitrile (77326-36-4) → 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one (405169-16-6)

Conditions	Yield
Stage #1: [6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]acetic acid ethyl ester; 2-amino-6-fluorobenzonitrile In toluene at 20 - 65℃; for 2h; Inert atmosphere; Stage #2: With potassium tert-butylate In toluene at 50℃; for 2h; Temperature;	88.4%
With potassium tert-butylate In tetrahydrofuran; toluene at 17 - 30℃; for 2h;	85.4%
Stage #1: [6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]acetic acid ethyl ester; 2-amino-6-fluorobenzonitrile In toluene at 63℃; Stage #2: With potassium tert-butylate In tetrahydrofuran; toluene at 17 - 30℃; for 2h; Product distribution / selectivity;	85.4%

2-amino-6-fluorobenzonitrile (77326-36-4) + 4-ethoxy-1,1,1-trichloro-3-buten-2-one (83124-74-7) → (Z)-2-fluoro-6-((4,4,4-trichloro-3-oxobut-1-en-1-yl)amino)benzonitrile

Conditions	Yield
In ethanol for 3h; Reflux;	88%

Hexafluorobenzene (392-56-3) + 2-amino-6-fluorobenzonitrile (77326-36-4) → 2-fluoro-6-(perfluorophenylamino)benzonitrile

Conditions	Yield
Stage #1: 2-amino-6-fluorobenzonitrile With potassium tert-butylate In tetrahydrofuran at 60℃; Glovebox; Stage #2: Hexafluorobenzene In tetrahydrofuran at 60℃; for 5h;	86%

(S)-1-(3-(hydroxymethyl)piperidin-1-yl)-3-methylbutan-1-one (1554631-83-2) + 2-amino-6-fluorobenzonitrile (77326-36-4) → (S)-2-amino-6-((1-(3-methylbutanoyl)piperidin-3-yl)methoxy)benzonitrile (1554631-80-9)

Conditions	Yield
Stage #1: (S)-1-(3-(hydroxymethyl)piperidin-1-yl)-3-methylbutan-1-one With sodium hydride In tetrahydrofuran; mineral oil at 0 - 25℃; for 1h; Stage #2: 2-amino-6-fluorobenzonitrile In tetrahydrofuran; mineral oil Reflux;	83.87%

2-amino-6-fluorobenzonitrile (77326-36-4) + sodium methylate (124-41-4) → 2-amino-6-methoxybenzonitrile (1591-37-3)

Conditions	Yield
With methanol In N,N-dimethyl-formamide at 20℃; for 18h; Inert atmosphere;	83%
In methanol; DMF (N,N-dimethyl-formamide) at 20℃; for 9h; Heating / reflux;	63%
In methanol; N,N-dimethyl-formamide at 20℃; for 9h; Heating / reflux;	63%

N-(2-(benzyloxy)ethyl)-3-hydroxy-2,2-dimethylpropanamide (1093206-04-2) + 2-amino-6-fluorobenzonitrile (77326-36-4) → 3-(3-amino-2-cyanophenoxy)-N-(2-(benzyloxy)ethyl)-2,2-dimethylpropanamide (1093206-03-1)

Conditions	Yield
	82%

carbon monoxide (201230-82-2) + (4-bromophenyl)thioanisole (104-95-0) + 2-amino-6-fluorobenzonitrile (77326-36-4) → 5-fluoro-2-(4-(methylthio)phenyl)quinazolin-4(3H)-one (1570097-49-2)

Conditions	Yield
With water; palladium diacetate; potassium carbonate; catacxium A In dimethyl sulfoxide at 120℃; under 7500.75 Torr; for 16h; Inert atmosphere; Autoclave;	82%

2-bromobenzo[2,3][1,4]oxazepino[7,6-b]quinoline + 2-amino-6-fluorobenzonitrile (77326-36-4) → 2-(benzo[2,3][1,4]oxazepino[7,6-b]quinolin-2-ylamino)-6-fluorobenzonitrile

Conditions	Yield
With chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); sodium t-butanolate In 1,4-dioxane at 90℃; for 0.75h; Buchwald-Hartwig Coupling; Microwave irradiation;	82%

2-amino-6-fluorobenzonitrile (77326-36-4) → 2-bromo-6-fluorobenzonitrile (79544-27-7)

Conditions	Yield
Stage #1: 2-amino-6-fluorobenzonitrile With sulfuric acid; sodium nitrite In water at 10℃; Stage #2: With hydrogen bromide; copper(I) bromide at 45℃;	81%
Stage #1: 2-amino-6-fluorobenzonitrile With hydrogen bromide; sodium nitrite In 1,4-dioxane; water at 0℃; for 3h; Stage #2: With hydrogen bromide; copper(I) bromide In 1,4-dioxane; water at 0 - 50℃; for 0.583333h;	70%
With copper(I) bromide; hydrogen bromide; sodium nitrite 1.)0 to -5 deg C, 1.5 h 2.)r.t., 15 h; Yield given. Multistep reaction;

bromobenzene (108-86-1) + carbon monoxide (201230-82-2) + 2-amino-6-fluorobenzonitrile (77326-36-4) → 5-fluor-2-phenylquinazolin-4(3Η)-one (1098336-86-7)

Conditions	Yield
With water; palladium diacetate; potassium carbonate; catacxium A In dimethyl sulfoxide at 120℃; under 7500.75 Torr; for 16h; Inert atmosphere; Autoclave;	81%

2-amino-6-fluorobenzonitrile (77326-36-4) + anthranilic acid nitrile (1885-29-6) → 5-fluor-2-phenylquinazolin-4(3Η)-one (1098336-86-7)

Conditions	Yield
Stage #1: anthranilic acid nitrile With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; butyraldehyde oxime In para-xylene at 70℃; for 12h; Inert atmosphere; Schlenk technique; Stage #2: 2-amino-6-fluorobenzonitrile In para-xylene at 110℃; for 4h; Inert atmosphere; Schlenk technique;	80%

2-amino-6-fluorobenzonitrile (77326-36-4) + benzaldehyde (100-52-7) → 5-fluor-2-phenylquinazolin-4(3Η)-one (1098336-86-7)

Conditions	Yield
Stage #1: 2-amino-6-fluorobenzonitrile With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; butyraldehyde oxime In para-xylene at 70℃; for 12h; Schlenk technique; Stage #2: benzaldehyde In para-xylene at 20 - 110℃; for 4h; Schlenk technique;	80%
With valeraldoxime In tert-Amyl alcohol at 125℃; for 15h; Inert atmosphere;	80%

2-methyl-2-((5-methylpyrimidin-2-yl)amino)propan-1-ol + 2-amino-6-fluorobenzonitrile (77326-36-4) → 2-amino-6-(2-methyl-2-((5-methylpyrimidin-2-yl)amino)propoxy)benzonitrile

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃; for 0.352833h; Inert atmosphere; Reflux;	80%

Upstream product

• 1897-52-5 2,6 difluorobenzonitrile 
• 372-19-0 meta-fluoroaniline 
• 545-06-2 trichloroacetonitrile 
• 1194-65-6 2,6-dichloro-benzonitrile 

Downstream Products

• 119584-70-2 2,4-diamino-5-fluoroquinazoline 
• 65610-13-1 3-fluoro-1,2-benzenedicarbonitrile 
• 79544-27-7 2-bromo-6-fluorobenzonitrile 
• 79544-29-9 2-fluoro-6-iodobenzonitrile 
• 143306-27-8 2-fluoro-6-nitrobenzonitrile 
• 77349-34-9 N-(2-Cyano-3-fluoro-phenyl)-oxalamic acid ethyl ester 
• 606145-77-1 N-(2-cyano-3-fluorophenyl)benzonitrile 
• 86505-94-4 2-amino-6-fluoro-benzoic acid,methyl ester 
• 148901-51-3 2-Fluoro-6-pyrrol-1-yl-benzonitrile 
• 1591-37-3 2-amino-6-methoxybenzonitrile 
• 878156-15-1 2-amino-6-(1-aminomethyl-propoxy)-benzonitrile 
• 405170-90-3 6-amino-2-(2-morpholin-4-ylethoxy)benzenecarbonitrile 
• 123241-47-4 2-phenoxy-6-aminobenzonitrile 
• 1093204-60-4 2-amino-6-isobutoxybenzonitrile 

Relevant articles and documents

Preparation method of 2,6-dibromoaniline

The invention discloses a preparation method of 2,6-dibromoaniline. According to the method, 2,6-difluorobenzonitrile is used as an initial raw material, and the 2,6-dibromoaniline is synthesized through six steps of reactions including ammonolysis, diazotization bromination, re-ammonolysis, re-diazotization bromination, amidation and Hofmann degradation. The 2,6-dibromoaniline obtained in the process is a brown solid, and the purity of the 2,6-dibromoaniline is 98% or above.

Changes in the activity and selectivity of herbicides by selective fluorine substitution, taking bentranil and classic analogues as examples

The introduction of fluorine atoms into 2-phenyl-4H-3,1-benzoxazin-4-one (bentranil) led to sweeping changes in its herbicidal properties in some cases, and 5-fluoro-2-phenyl-4H-3,1-benzoxazin-4-one ('fluorobentranil') was found to be the most active compound. It can be prepared from 2-amino-6-fluoro-benzoic acid or by direct halogen exchange of 5-chloro-2-phenyl-4H-3,1-benzoxazin-4-one. The latter reaction was investigated on a pilot scale, including a high-temperature (350°C) potassium fluoride halogen exchange without solvent. When sulfolane was used as a solvent, a side reaction at 220°C - partial decomposition to a diphenylether - could be prevented by addition of a small amount of a radical scavenger. Other intermediates with a pseudohalogen substitution were obtained by side-chain chlorination of suitable methylsulfanyl benzoic acid precursors and halogen exchange. 'Fluorobentranil' shows good broad-leaf activity and selectivity on rice, cereals and maize. In a second case study, the fluoro-substituted anthranilic acids mentioned above were also found to be appropriate for synthesizing herbicidal sulfonylurea (SU) compounds via Meerwein reaction of their aniline function. Methyl 2-[({[(4-chloro-6-methoxy-2- pyrimidinyl)-amino]carbonyl}amino)sulfonyl]-6-fluorobenzoate is an example of a SU that is compatible with maize, whereas the unsubstituted Classic analogue is not selective.

Ambident Behavior of Ketone Enolate Anions in SNAr Substitutions on Fluorobenzonitrile Substrates

2,6-Difluorobenzonitrile was found to be a suitable substrate for studying carbon versus oxygen nucleophilic attack by enolate anions of weakly acidic ketones.The influence of the nucleophile structure and the solvent are investigated.The charge control character of the reaction and the influence of the substrate are discussed.