1-Phenylcyclopropanecarbonitrile

Clear colorless to slightly yellow liquid

Step 1: Preparation of l-phenylcyclopropanecarbonitrileTo a stirred solution of phenylacetonitrile (100 g, 0.8547 mol) in aqueous solution of KOH (447g in 420 mL of water) and 2.7g of tetrabutyl ammonium bromide was added 1, 2-dibromoethane (147ml, 1.709mol) drop wise by maintaining exothermicity at 50 °C.The reaction mixture was stirred at 50 °C for 1 hr, and then poured in cold water and extracted in diisopropyl ether .Crude product was purified by high vacuum distillation which afforded 90g of colourless liquid compound in 73 percent yield.2-Phenyl-2-cyclopropyl ethylamine; To a cooled solution of 2-phenylacetonitrile (5.85 g, 50 mmol) in THF (200 ml) was added potassium bis (trimethylsiylyl) amide (29.92 g, 150 MMOL). The resulting mixture was stirred under N2 at 0°C for 30 min. To the resulting mixture was added dropwise a solution of 1, 2-dibromoethane (10.33 g, 55 mmol) in THF (30 ml). The reaction mixture was stirred under N2 at 0°C and gradually allowed to warm to room temperature. Then it was stirred at room temperature overnight. It was concentrated in vacuo. The 1-PHENYL-1-CYCLOPROPANECARBONITRILE was obtained by distillation (3.6 g, 50percent). 1H NMR (CDC13, 300 MHz) 8 7.27-7. 38 (m, 5H), 1.69-1. 76 (m, 2H), 1.37-1. 44 (m, 2H). 1-PHENYL-1-CYCLOPROPANECARBONITRILE (1.0 g, 6.98 mmol) was added to a stirred suspension of lithium aluminum hydride (0.27 g, 6.98 mmol) in ether (25 ml). The resulting suspension was refluxed for 2 hrs, them cooled to 0°C by applying an external ice bath. The excess hydride was quenched by careful addition of H2O. The resulting mixture was filtered. The solid was washed with ether and filtered. The filtrate was dried (MgS04), and filtered. The filtrate was concentrated in vacuo to give 2-CYCLOPROPYL-2-PHENYLETHYLAMINE. HNMR (DMSO-d6, 300 MHz) 8 7.28 (M, 4H), 7.17 (M, 1H), 2.70 (s, 2H), 1.45 (br s, 2H), 0.78 (dd, J = 6.2, 3.8 H, 2H), 0.67 (dd, J = 6. 2, 3. 8HZ, 2H).Step (v): Synthesis of 1-phenylcyclopropanecarbonitrileExperimental procedure : To a solution of NaH ( 12.6 g, 525 mmoles) in DMSO (300 mL) was added phenylacetonitrile (20 g, 170.9 mmoles) in DMSO at 0 °C and the mixture was stirred for 5 min. 1, 2 dibromoethane (16.29 mL 86.6 mmoles) in DMSO was added to the reaction mixture and the contents were stirred for 2 h at about 20-35 °C. The reaction mixture was treated with isopropanol (10 mL), ice cold water (150 mL) and extracted with ethyl acetate (200 mL). The organic layer was washed with brine solution (2 x 100 mL), dried over NaPreparation of 1-phenylcyclopropanecarbonitrile General procedure: Ethylene carbonate (30.0 eq.) was loaded at room temperature in a 100 ml reactor. The internal temperature of the reactor was brought to 50C. After all the solid was melted, 0.05 eq. of PEG-200 and the compound of Formula (II) (1.0 eq.) (see table 1) were charged in the reactor. 3, 1 eq. of potassium tert-butoxide were added portion-wise under stirring to the resulting clear colorless solution. Then, the mixture was heated to 126-135C and kept under stirring until complete reaction, for about 4-8 hours. The mixture was cooled to 50C and then toluene and deionised water were added. The mixture was kept under stirring for 15 minutes, then the stirring was stopped. The aqueous layer was discharged and the organic phase was washed three times with deionised water. The organic layer was concentrated to dryness at reduced pressure to obtain the end product with a molar yield reported in table 1.To a stirred solution of sodium hydride (60%) (16.4 g) in dry DMSO (160 mL), benzyl cyanide (20 g) in THF (20 mL) was slowly added under nitrogen atmosphere at 0C. The reaction mixture was stirred at 0C for 30 minutes, before bromo chloro ethane (29 g) in dry THF (20 mL) was added dropwise under nitrogen atmosphere at 0C. After stirring at room temperature for 2 hours, the reaction was slowly quenched with saturated ammonium chloride solution (250 mL). The reaction mixture was diluted with ethyl acetate (500 mL) and the aqueous phase was extracted with ethyl acetate (2 x 100 mL). The combined organic layer was washed with brine (250 mL) and dried over anhydrous Na2S04. Evaporation of solvents under reduced pressure gave crude 1- phenylcyclopropanecarbonitrile (20 g) as a yellow liquid, which was used as was for further reaction. XH-NMR (CDC13): delta 1.48-1.55(m, 2H), 1.66-1.73 (m, 2H), 7.30-7.40 (m, 5H).

Molecular Weight:143.18
XLogP3:1.9
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:143.073499291
Monoisotopic Mass:143.073499291
Topological Polar Surface Area:23.8
Heavy Atom Count:11
Complexity:188
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes