4-BROMOPHTHALONITRILE

Synthetic Synthesis of 4-bromophthalonitrile (hereinafter abbreviated as 4-BPN);4-BPN represented as the formula (22) was synthesized from 4-BPA, obtained in Synthetic Example 3, according to the following procedure with reference to Synthesis, 1993, pp. 194-196. In a 200-ml eggplant flask, 100 ml of dried N, N-dimethylformamide was placed in which 70 ml of thionyl chloride was dropped so as not to allow a rise of temperature over 5°C while stirring in an ice bath of 0°C. After completion of the dropping, tha mixture was allowed to stand at 0°C for two hours. Next, 20.9032 g (0.086 mols) of 4-BPA was gently added to in the form of powder so as not to permit a rise of temperature over 5°C. Subsequently, while keeping the reaction temperature within 0 to 5°C, the reaction was carried out for five hours, followed by removing the ice bath and raising the temperature up to 23°C and carrying out the reaction for 24 hours while keeping the temperature. After completion of the reaction, the reaction solution in the form of a whitish yellow suspension was gently poured into a one-liter beaker in which 300 g of ice pieces was placed. Precipitated whitish yellow crystals were filtrated under reduced pressure, washed with 100 ml of pure water and further washed with 100 ml of methanol. Ten times by weight of methanol was added to the whitish yellow crude product, which was completely dissolved by use of an oil bath and stored at 23°C for recrystallization. The resulting white crystals were dried for 24 hours with a reduced pressure dryer to obtain 17.80 g (yield: 80percent) of 4-BPN as white crystals. The thus obtained white crystals were subjected to identification of the structure thereof from NMR spectra and confirmed as 4-BPN. Compound E-1 (110 mmmol) was refluxed in formamide for 4 hours to obtain compound E-2 (103 mmol, 94percent).Compound E-2 (100 mmol) was reacted in 28percent ammonia solution at room temperature for 24 hours to obtain compound E-3 (74 mmol, 74percent).Compound E-3 (70 mmol) was dissolved in DMF, The mixture was allowed to react with thionyl chloride in an ice bath for 24 hours to obtain compound E-4 (53 mmol, 75percent).Synthetic Synthesis of 4-bromophthalonitrile (hereinafter abbreviated as 4-BPN); [Show Image] 4-BPN represented as the formula (22) was synthesized from 4-BPA, obtained in Synthetic Example 3, according to the following procedure with reference to Synthesis, 1993, pp. 194-196. In a 200-ml eggplant flask, 100 ml of dried N, N-dimethylformamide was placed in which 70 ml of thionyl chloride was dropped so as not to allow a rise of temperature over 5C while stirring in an ice bath of 0C. After completion of the dropping, the mixture was allowed to stand at 0C for two hours. Next, 20.9032 g (0.086 mols) of 4-BPA was gently added to in the form of powder so as not to permit a rise of temperature over 5C. Subsequently, while keeping the reaction temperature within 0 to 5C, the reaction was carried out for five hours, followed by removing the ice bath and raising the temperature up to 23C and carrying out the reaction for 24 hours while keeping the temperature. After completion of the reaction, the reaction solution in the form of a whitish yellow suspension was gently poured into a one-liter beaker in which 300 g of ice pieces was placed. Precipitated whitish yellow crystals were filtrated under reduced pressure, washed with 100 ml of pure water and further washed with 100 ml of methanol. Ten times by weight of methanol was added to the whitish yellow crude product, which was completely dissolved by use of an oil bath and stored at 23C for recrystallization. The resulting white crystals were dried for 24 hours with a reduced pressure dryer to obtain 17.80 g (yield: 80%) of 4-BPN as white crystals. The thus obtained white crystals were subjected to identification of the structure thereof from NMR spectra and confirmed as 4-BPN. 1H-NMR (ppm/CDCl3):7.96(dd, 1H), 7.90(dd, 1H), 7.67(d, 1H).Compound E-1 (110 mmmol) was refluxed in formamide for 4 hours to obtain compound E-2 (103 mmol, 94%).Compound E-2 (100 mmol) was reacted in 28% ammonia solution at room temperature for 24 hours to obtain compound E-3 (74 mmol, 74%).Compound E-3 (70 mmol) was dissolved in DMF, The mixture was allowed to react with thionyl chloride in an ice bath for 24 hours to obtain compound E-4 (53 mmol, 75%).Synthetic Synthesis of diethyl-(3, 4-dicyanophenyl)phosphonate (hereinafter abbreviated as 4-P=O(OEt); 2PN) [Show Image] 4-P=O(OEt)2PN represented as the formula (23) was synthesized from 4-BPN, obtained in Synthetic Example 4, according to the following procedure (reaction formula 5) with reference to Helvetica Chimica Acta, 2004, pp. 825-844. In a 50-ml eggplant flask, 3.1055 g (15 mmols) of 4-BPN was placed and the system was purged with nitrogen, followed by adding 0.1944 g (0.15 mmols, 0.1 equivalents relative to 4-BPN) of nickel (II) chloride and further purging the system with nitrogen. Next, 3.42 ml (d = 0.97, 20 mmols, 1.3 equivalents relative to 4-BPN) of triethyl phosphite was added by means of a syringe on an oil bath of 160C, followed by reaction for one hour while keeping the temperature at 160C under stirring. After completion of the reaction, the crude product obtained as a reddish green viscous liquid was purified by use of silica gel column chromatography using silica gel 7734 (0.063 to 0.02 mm), made by Merck Co., & Inc., as a solid phase and chloroform as an eluate to obtain 2.65 g (yield: 67%) of a colorless transparent liquid of 4-P=O(OEt)2PN. The thus obtained colorless transparent liquid was identified from NMR with respect to the structure thereof and confirmed as 4-P=O(OEt)2PN. 1H-NMR (ppm/CDCl3):8.19(s, 1H), 7.94(d, 1H), 7.77(d, 1H), 4.18(m, 4H), 1.35(tt, 6H).In a 250 ml round bottom flask, H001-3 (15 mmol), cuprous iodide (30 mmol), t-BuOK (20 mmol) and A roundbottomedflask equipped with a reflux condenser and athermometer was charged with 1 g (0.0048 mol) of4-bromo-phthalonitrile (0.414 g), 4-borate-4', 4'-dimethoxytriphenylamine (1.725 g), Tetrakis(triphenylphosphine)palladium (0.231 g) and potassium carbonate (2.764 g) were placed in a mixed solution of water (3 mL) and tetrahydrofuran (50 mL). Nitrogen gas was used as a shielding gas, and aeration-degassing was carried out three times to obtain a nitrogen atmosphere. Then, the mixture was stirred at 80 C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and magnesium sulfate was added to remove water; the solution after water removal was dried. To obtain a solid product, The obtained solid product was subjected to column chromatography using an eluent (petroleum ether: ethyl acetate: dichloromethane in a volume ratio of 20:1:2); after column chromatography, The obtained solution was spin-dried to obtain an phthalic acid derivative, which was confirmed by nuclear magnetic analysis.Its structure is as shown in Formula I, which is 4-o-phenylenedicyano-4', 4'-dimethoxytriphenylamine. The nuclear magnetic analysis chart is shown in Figure 1;General procedure: A 10 mL Schlenk tube equipped with a stir bar was sealed with a rubber septum, It was dried using a heat gun under reduced pressure (about 400 C.)It was then filled with argon.Further, reduced pressure - argon filling was repeated twice to make the inside of the Schlenk tube completely under an argon atmosphere.0.5 mL of N, N'-dimethylpropyleneurea (hereinafter referred to as DMPU) as a solvent, 0.71 mL of diethylzinc (1.02 M hexane solution: 1.5 eq), 386.25 mg of nonafluorobutyl iodide (1.125 mmol, 2.25 eq) were sequentially added at room temperature using a syringe.Further, 0.5 mmol of 208.2 mg of dodecyl 2-iodobenzoate (0.5 mmol, 1 equivalent) as an electrophile, 9.5 mg of copper iodide (0.05 mmol: 0.1 eq) was added, After replacing the rubber septum with a glass stopper, it was heated at 90 C. for 16 hours.After allowing the reaction mixture to cool to room temperature, the reaction was stopped with 20 mL of 1 N hydrochloric acid, And extracted three times with diethyl ether having a total volume of 100 mL.The combined organic layer was washed with saturated brine, After drying with magnesium sulfate, the solvent was distilled off with a rotary evaporator.The crude product was purified by flash column chromatography (methylene chloride / hexane 1: 7)226.2 mg of the desired product was obtained (89%, pale yellow oil).

Molecular Weight:207.03
XLogP3:2.1
Hydrogen Bond Acceptor Count:2
Exact Mass:205.94796
Monoisotopic Mass:205.94796
Topological Polar Surface Area:47.6
Heavy Atom Count:11
Complexity:231
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes