2-Amino-6-fluorobenzonitrile

white to light yellow crystal powder

A mixture [OF 2, 6-DIFLUOROBENZONITRILE] (19.0 g, 137 mmol) and ethanol (200 ml) pre-saturated with ammonia gas was heated at [140°C] in an autoclave for 6 h (terminal pressure 200 psi). The mixture was allowed to cool to ambient temperature, evaporated to dryness and triturated with water (200 ml). The solid was filtered and left to air-dry to afford 2-amino- 6-fluorobenzonitrile (18.0 g, 97percent) as an off-white solid: [8H] (360 MHz, [CDCL3)] 4.53 (3H, s), 6.44-6. 52 (2H, m), 7.24-7. 30 [(1H, M).] 2-Amino-6-fluorobenzonitrile (18.0 g, 132 mmol) was dissolved in hot 1, 4-dioxane (20 ml), 48percent hydrobromic acid (200 [ML)] was added and the mixture cooled to [0°C] before dropwise addition of sodium nitrite (10.5 g, 152 mmol) in water (20 [ML)] over 1.5 h. The resulting mixture was stirred at 0°C for 1.5 h then poured onto a cooled [(0°C)] solution of copper [(I)] bromide (56.8 g, 396 mmol) in 48percent hydrobromic acid (50 ml). The solution was stirred at [0°C] for 15 min then heated at [50°C] for 20 min. The mixture was cooled to ambient temperature, diluted with water (1200 [ML)] and extracted with ethyl acetate (2 x 400 [ML).] The combined organics were washed with [10percent] aqueous ammonia solution (400 ml), water (400 ml) and brine (500 ml), dried over anhydrous magnesium sulphate, filtered and evaporated to give an orange oil. Purification by chromatography on silica gel, eluting with isohexane on a gradient of ethyl acetate (2-4percent), gave 2- bromo-6-fluorobenzonitrile (18.5 g, 70percent) as a white solid: [8H] (400 MHz, [CDCL3)] 7.17-7. 23 [(1H, ] ddd, [J8, 8] and 1), 7.44-7. 52 (2H, m). [2-BROMO-6-FLUOROBENZONITRILE] and [2- (2-FLUORO-5-NITROPHENYL)-4, ] 4, 5, 5- tetramethyl- [1, 3, [2]] dioxaborolane were coupled following the procedure in to afford 3, 2'-difluoro-5'-nitrobiphenyl-2-carbonitrile as a black solid: [5H] (360 MHz, [CDCL3)] 7.32-7. 44 (3H, m), 7.71-7. 77 [(1H, ] m), 8. 35-8. 41 (2H, m). 3, [2APOS;-DIFLUORO-5APOS;-NITROBIPHENYL-2-CARBONITRILE] was reduced following the procedure in to give 5'-amino-3, 2'-difluorobiphenyl-2- carbonitrile as a brown solid: [SN] (360 MHz, [CDCL3)] 3.74 (2H, s), 6.66-6. 75 (2H, m), 7.01 [(1H, ] dd, J 9 and 9), 7.19-7. 30 (2H, m), 7.59-7. 65 [(1H, ] m). 5'-Amino-3, 2'-difluorobiphenyl-2-carbonitrile was bromo-de- aminated following the procedure in to give 5'-bromo-3, 2'- difluorobiphenyl-2-carbonitrile as a white solid: AH (400 MHz, [CDCL3)] 7.13 [(1H, ] dd, J 9 and 9), 7.27-7. 30 (2H, m), 7.53-7. 59 (2H, m), 7.64-7. 69 [(1H, ] m). [5APOS;-BROMO-3, ] [2APOS;-DIFLUOROBIPHENYL-2-CARBONITRILE WAS] converted, following the procedure in Example 2, to 3, [2APOS;-DIFLUORO-5APOS;- (5, ] 5-dimethyl- [1, 3, 2] dioxaborinan-2-yl) biphenyl-2-carbonitrile, a brown oil that crystallised on standing: [SN] (360 MHz, [CDCL3)] 1.03 (6H, s), 3.77 (4H, s), 7.17-7. 25 (2H, m), 7.30 [(1H, ] d, J8), [7.] 59-7.65 [(1H, ] m), 7.81-7. 91 (2H, m). 3-Bromo-8-fluoro-7- [(1-HYDROXY-1-METHYLETHYL)] imidazo [1, 2-a] pyridine (0.10 g, 0.36 mmol) and 3, [2APOS;-DIFLUORO-5APOS;- (5, 5-DIMETHYL- [1, ] 3, 2] [DIOXABORINAN-] 2-yl) biphenyl-2-carbonitrile (0.16 g, 0.47 mmol) were coupled following the procedure in to afford [3, 2APOS;-DIFLUORO-5APOS;- [8-FLUORO-7- (L-HYDROXY-L-] methylethyl) imidazo [1, 2-a] pyridin-3-yl] biphenyl-2-carbonitrile as a white amorphous solid (110 mg, 74percent): [8H] (360 MHz, [CDCL3)] 1.73 (6H, s), 2.10 [(1H, ] s), 7.21 [(1H, ] dd, J 7 and 7), 7.30 [(1H, ] dd, J 8 and [8), 7. 38-7.] 44 (2H, m), 7.61-7. 72 (4H, m), 8. 23 [(1H, ] d, [J 7) ; M/Z] (ES+) [408] [(M++H).]

Used as pesticide and pharmaceutical intermediate

Molecular Weight:136.13
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:136.04367633
Monoisotopic Mass:136.04367633
Topological Polar Surface Area:49.8
Heavy Atom Count:10
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes