Method for preparing phenylboronic acid neopentyl glycol ester

Abstract

The present invention discloses a method for preparing a phenylboronic acid neopentyl glycol ester. A mixed nickel(II) complex with a formula of Ni[P(OR.sup.1).sub.3][(R.sup.2NCH.sub.2CH.sub.2NR.sup.2)C]X.sub.2 is used as a catalyst. The method comprises: in the presence of potassium methoxide, efficiently catalyze a cross coupling reaction between a phenyl chloride and a bis(neopentyl glycolato)-diboron to prepare a phenylboronic acid neopentyl glycol ester. The invention provides the first embodiment of using a mixed nickel(II) complex with phosphonate ester and nitrogen heterocyclic carbene ancillary ligands to catalyze a cross coupling reaction.

Claims

1. A method for preparing phenylboronic acid neopentyl glycol ester, comprising the steps of: sequentially adding catalyst, potassium methoxide, bis(neopentyl glycolato)-diboron, phenyl chloride and organic solvent in an inert gas atmosphere; reacting at 40 C. for 6 hours to obtain phenylboronic acid neopentyl glycol ester; the phenyl chloride is p-chlorophenol, p-chloroaniline, p-chlorobenzophenone or p-cyanochlorobenzene; the catalyst is used in an amount of 5% by mole of the phenyl chloride; the chemical structure of the catalyst is as follows: ##STR00002## wherein R.sup.1 is ethyl or isopropyl; R.sup.2 is 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl or tert-butyl; and X is bromine or chlorine.

2. The method for preparing phenylboronic acid neopentyl glycol ester according to claim 1, characterized in that after the reaction is completed, the reaction is terminated with water, the reaction product is extracted with ethyl acetate, and finally subjected to column chromatography to obtain phenylboronic acid neopentyl glycol ester.

3. The method for preparing phenylboronic acid neopentyl glycol ester according to claim 1, characterized in that the inert gas is argon; and the organic solvent is 1,4-dioxane.

4. The method for preparing phenylboronic acid neopentyl glycol ester according to claim 1, characterized in that the molar ratio of the catalyst, potassium methoxide, bis(neopentyl glycolato)-diboron and phenyl chloride is 0.05:1.5:1.5:1.

5. The method for preparing phenylboronic acid neopentyl glycol ester according to claim 1, characterized in that the catalyst is prepared as follows: when X is bromine, the bis(phosphite) nickel dibromide and the nitrogen heterocyclic carbene are dissolved in a solvent in an inert gas, and reacted at room temperature for 2 to 4 hours; then the solvent is removed in vacuo, and the residue is extracted with toluene after washed with an n-hexane, and the clear solution was transferred and removed the solvent toluene to obtain a nickel (II) complex that is catalyst; when X is chlorine, in an inert gas, the bis(triphenylphosphine)nickel dichloride and nitrogen heterocyclic carbene are dissolved in a solvent, and reacted at room temperature for 2 to 4 hours; then the solvent is removed in vacuo, and the residue is extracted with toluene after washed with an n-hexane, the clear solution is transferred and removed the solvent toluene to obtain nickel (II) complex containing triphenylphosphine and nitrogen heterocyclic carbene; then dissolving the mixed nickel (II) complex and phosphite in a solvent, and reacted at room temperature for 1 hour; then the solvent was removed in vacuo, the residue was washed with n-hexane and then extracted with toluene, and the clear solution was transferred and removed the solvent toluene to obtain nickel(II) complex, which was the catalyst.

6. The method for preparing phenylboronic acid neopentyl glycol ester according to claim 5, characterized in that in the preparation method of the catalyst, the inert gas is argon; the molar ratio of the bis(phosphite) nickel dibromide to the nitrogen heterocyclic carbene is 1:1; the molar ratio of bis(triphenylphosphine)nickel dichloride to nitrogen heterocyclic carbene is 1:1; the molar ratio of the mixed nickel (II) complex containing triphenylphosphine to the nitrogen heterocyclic carbene to the phosphite is 1:1; the solvent is tetrahydrofuran.

Description

EXAMPLES FOR THE INVENTION

Detailed Description of the Embodiments

(1) The present invention is further described below in conjunction with the embodiments:

Example 1: Synthesis of Ni[P(OR.SUP.1.).SUB.3.][(R.SUP.2.NCH.SUB.2.CH.SUB.2.NR.SUP.2.)C]X.SUB.2 .(R.SUP.1.=CH.SUB.2.CH.SUB.3., R.SUP.2.=2,4,6-trimethylphenyl, X=Br)

(2) Add a nitrogen heterocyclic carbene (R.sup.2NCH.sub.2CH.sub.2NR.sup.2) C (0.2464 g, 0.8 mmol) to the solution of di(triethyl phosphite) nickel dibromide (0.4400 g, 0.8 mmol) in tetrahydrofuran, react at room temperature for 2 hours, the solvent was removed in vacuum, the residue was washed with n-hexane, and the obtained residue is extracted by toluene, and the clear liquid is transferred, and solvent toluene is removed, so as to obtain a red solid, wherein the yield is 68%.

(3) The results of elemental analysis of the product are shown in Table 1:

(4) TABLE-US-00001 TABLE 1 Elemental analysis results C: (%) H: (%) N: (%) Theoretical value 46.86 6.12 4.05 Actual value 47.04 6.21 3.99

(5) The product was subjected to nuclear magnetic characterization and the results are as follows:

(6) The product was dissolved in C.sub.6D.sub.6 (ca. 0.4 mL), sealed, and characterized by Unity Inova-400 NMR apparatus at room temperature: .sup.1H NMR (400 MHz, C.sub.6D.sub.6): 6.88 (s, 4H), 3.97 (s, 6H), 3.13 (s, 4H), 2.64 (s, 12H), 2.15 (s, 6H), 1.02 (s, 9H) ppm.

Example 2: Synthesis of Ni[P(OR.SUP.1.).SUB.3.][(R.SUP.2.NCH.SUB.2.CH.SUB.2.NR.SUP.2.)C]X.SUB.2.=CH.SUB.2.CH.SUB.3., R.SUP.2.=2,6-diisopropylphenyl, X=Br)

(7) Add a nitrogen heterocyclic carbene (R.sup.2NCH.sub.2CH.sub.2NR.sup.2) C (0.3627 g, 0.93 mmol) to a solution of bis(triethyl phosphite) nickel dibromide (0.5115 g, 0.93 mmol) in tetrahydrofuran, react at room temperature for 2 hours, the solvent was removed in vacuum, the residue was washed with n-hexane, and the obtained residue is extracted by toluene, and the clear liquid is transferred, and solvent toluene is removed, so as to obtain a red crystals, wherein the yield is 77%.

(8) The results of elemental analysis of the product are shown in Table 2:

(9) TABLE-US-00002 TABLE 2 Elemental analysis C: (%) H: (%) N: (%) Theoretical value 51.06 7.01 3.61 Actual value 51.33 7.19 3.49

(10) The product was subjected to nuclear magnetic characterization and the results are as follows:

(11) The product was dissolved in C.sub.6D.sub.6 (ca. 0.4 mL), sealed, and characterized by Unity Inova-400 NMR apparatus at room temperature: .sup.1H NMR (400 MHz, C.sub.6D.sub.6): 7.29 (s, 6H), 3.91 (d, 6H), 3.88-3.71 (m, 4H), 3.58 (s, 4H), 1.75 (d, 12H), 1.18 (d, 12H), 1.02 (s, 9H) ppm.

Example 3: Synthesis of Ni[P(OR.SUP.1.).SUB.3.][(R.SUP.2.NCH.SUB.2.CH.SUB.2.NR.SUP.2.)C]X.SUB.2.=CH(CH.SUB.3.).SUB.2., R.SUP.2.=2,6-diisopropylphenyl, X=Br)

(12) Add a nitrogen heterocyclic carbene (R.sup.2NCH.sub.2CH.sub.2NR.sup.2) C (0.3627 g, 0.93 mmol) to a solution of di(triisopropyl phosphite) nickel dibromide (0.5905 g, 0.93 mmol) in tetrahydrofuran, and react at room temperature for 3 hours. The solvent was removed in vacuo, and the residue was washed with n-hexane, and the residue obtained was extracted with toluene, and the clear liquid was transferred and remove the solvent toluene to give red-black crystals in a yield of 70%.

(13) The results of elemental analysis of the product are shown in Table 3:

(14) TABLE-US-00003 TABLE 3 Elemental analysis C: (%) H: (%) N: (%) Theoretical value 52.84 7.39 3.42 Actual value 53.11 7.51 3.28

(15) The product was subjected to nuclear magnetic characterization. The results were as follows: The product was dissolved in C.sub.6D.sub.6 (about 0.4 mL), sealed, and characterized on a Unity Inova-400 NMR apparatus at room temperature: .sup.1H NMR (400 MHz, C.sub.6D.sub.6): 7.28 (s, 6H), 4.94 (s, 3H), 3.83 (s, 4H), 3.57 (s, 4H), 1.73 (s, 12H), 1.16 (s, 30H) ppm.

Example 4: Synthesis of Ni[P(OR.SUP.1.).SUB.3.][(R.SUP.2.NCH.SUB.2.CH.SUB.2.NR.SUP.2.)C]X.SUB.2 .(R=CH.SUB.2.CH.SUB.3., R.SUP.2.=C(CH.SUB.3.).SUB.3., X=Br)

(16) Add a nitrogen heterocyclic carbene (R.sup.2NCH.sub.2CH.sub.2NR.sup.2) C (0.1438 g, 0.78 mmol) to a solution of di(triethyl phosphite) nickel dibromide (0.4290 g, 0.78 mmol) in tetrahydrofuran, react at room temperature for 1 hour, the solvent was removed in vacuum, the residue was washed with n-hexane, and the obtained residue is extracted by toluene, and the clear liquid is transferred, and solvent toluene is removed, so as to obtain a yellow solid, wherein the yield is 60%. The results of elemental analysis of the product are shown in Table 4:

(17) TABLE-US-00004 TABLE 4 Elemental analysis C: (%) H: (%) N: (%) Theoretical value 35.95 6.74 4.93 Actual value 36.22 6.88 4.81

(18) The product was subjected to nuclear magnetic characterization and the results are as follows:

(19) The product was dissolved in C.sub.6D.sub.6 (ca. 0.4 mL), sealed, and characterized on a Unity Inova-400 NMR apparatus at room temperature: .sup.1H NMR (400 MHz, C.sub.6D.sub.6): 4.29-4.07 (m, 5H), 2.73 (t, 4H), 2.26 (s, 6H), 2.00 (s, 9H), 1.10 (dt, 9H), 0.45 (s, 4H) ppm.

Example 5: Synthesis of Ni[P(OR.SUP.1.).SUB.3.][(R.SUP.2.NCH.SUB.2.CH.SUB.2.NR.SUP.2.)C]X.SUB.2 .(R.SUP.1.=CH.SUB.2.CH.SUB.3., R.SUP.2.=C(CH.SUB.3.).SUB.3., X=Cl)

(20) Add a nitrogen heterocyclic carbene (R.sup.2NCH.sub.2CH.sub.2NR.sup.2)C (0.1438 g, 0.78 mmol) to a solution of bis(triphenylphosphine)nickelchloride (0.5101 g, 0.78 mmol) in tetrahydrofuran, react at room temperature for 1 hour, and remove solvent in vacuo. The residue was washed with n-hexane, and the residue obtained was extracted with toluene, and the clear liquid is transferred, and solvent toluene is removed to give a pink solid, wherein the yield is 65%. Further, the pink solid (0.2870 g, 0.5 mmol) was mixed with triethyl phosphite (86 L, 0.5 mmol), and tetrahydrofuran was added as a solvent, and the mixture was reacted at room temperature for 1 hour, and the solvent was evaporated in vacuo. The residue was washed with n-hexane, and the residue obtained was extracted with toluene, and t the clear liquid is transferred, and solvent toluene is removed to give a yellow solid, wherein the yield is 90%.

(21) The results of elemental analysis of the product are shown in Table 5:

(22) TABLE-US-00005 TABLE 5 Elemental analysis C: (%) H: (%) N: (%) Theoretical value 42.62 8.00 5.85 Actual value 42.95 8.11 5.73

(23) The product was subjected to nuclear magnetic characterization and the results are as follows:

(24) The product was dissolved in C.sub.6D.sub.6 (ca. 0.4 mL), sealed, and characterized on a Unity Inova-400 NMR apparatus at room temperature: .sup.1H NMR (400 MHz, C.sub.6D.sub.6): 4.21 (dp, 6H), 2.91-2.59 (m, 4H), 2.31 (s, 6H), 2.04 (s, 12H), 1.20 (t, 3H), 1.00 (t, 6H) ppm.

Example 6: Ni[P(OR.SUP.1.).SUB.3.][(R.SUP.2.NCH.SUB.2.CH.SUB.2.NR.SUP.2.)C]X.SUB.2.=CH.SUB.2.CH.SUB.3., R.SUP.2.=2,4,6-trimethylphenyl, X=Br) Catalyzed Cross-Coupling Reaction of p-Chlorophenol and Bis(Neopentyl Glycolato)-Diboron

(25) Under argon protection, catalyst (17.3 mg, 0.025 mmol, 5 mol %), potassium methoxide (52.6 mg, 0.75 mmol), bis(neopentyl glycolato)-diboron (169.5 mg, 0.75 mmol), p-chlorophenol (49 l, 0.50 mmol), 1.5 ml of 1,4-dioxane were sequentially added to the reaction flask, reacted at 40 C. for 6 hours, and quenched with water, the product was extracted with ethyl acetate and purified by column chromatography (a mixed solvent of ethyl acetate/petroleum ether in a volume ratio of 1:5 was used as a developing solvent), and the yield was 54%.

(26) The product was dissolved in CDCl.sub.3 (ca. 0.4 mL), sealed, and characterized on a Unity Inova-400 NMR apparatus at room temperature: .sup.1H NMR (400 MHz, CDCl.sub.3, TMS): 7.70 (d, 2H), 6.81 (d, 2H), 5.35 (s, 1H), 3.75 (s, 4H), 1.01 (s, 6H) ppm.

Example 7: Ni[P(OR.SUP.1.).SUB.3.][(R.SUP.2.NCH.SUB.2.CH.SUB.2.NR.SUP.2.)C]X.SUB.2 .(R.SUP.1.=CH.SUB.2.CH.SUB.3., R.SUP.2.=2,4,6-trimethylphenyl, X=Br) Catalyzed Cross-Coupling Reaction of p-Chloroaniline and Bis(Neopentyl Glycolato)-Diboron

(27) Under argon protection, catalyst (17.3 mg, 0.025 mmol, 5 mol %), potassium methoxide (52.6 mg, 0.75 mmol), bis(neopentyl glycolato)-diboron (169.5 mg, 0.75 mmol), p-chloroaniline (63.8 mg, 0.50 mmol), 1.5 ml of 1,4-dioxane were sequentially added to the reaction flask, reacted at 40 C. for 6 hours, and quenched with water, and the product was extracted with ethyl acetate and purified by column chromatography (a mixed solvent of ethyl acetate/petroleum ether in a volume ratio of 1:5 was used as a developing solvent), and the yield was 66%.

(28) The product was dissolved in CDCl.sub.3 (ca. 0.4 mL), sealed, and characterized on a Unity Inova-400 NMR apparatus at room temperature: .sup.1H NMR (400 MHz, CDCl.sub.3, TMS): 7.61 (d, 2H), 6.66 (d, 2H), 3.78 (s, 2H), 3.74 (s, 4H), 1.01 (s, 6H) ppm.

Example 8: Ni[P(OR.SUP.1.).SUB.3.][(R.SUP.2.NCH.SUB.2.CH.SUB.2.NR.SUP.2.)C]X.SUB.2 .(R.SUP.1.=CH.SUB.2.CH.SUB.3., R.SUP.2.=2,4,6-trimethylphenyl, X=Br) Catalyzed Cross-Coupling Reaction of p-Chlorobenzophenone and Bis(Neopentyl Glycolato)-Diboron

(29) Under argon protection, catalyst (17.3 mg, 0.025 mmol, 5 mol %), potassium methoxide (52.6 mg, 0.75 mmol), bis(neopentyl glycolato)-diboron (169.5 mg, 0.75 mmol), p-chlorobenzophenone (108 mg, 0.50 mmol), 1.5 ml of 1,4-dioxane were sequentially added to the reaction flask, reacted at 40 C. for 6 hours, quenched with water, and the product was extracted with ethyl acetate. The product was extracted with ethyl acetate and purified by column chromatography (mixed solvent of ethyl acetate/petroleum ether in a volume ratio of 1:20 as a developing solvent) in a yield of 58%.

(30) The product was dissolved in CDCl.sub.3 (ca. 0.4 mL), sealed, and characterized on a Unity Inova-400 NMR apparatus at room temperature: .sup.1H NMR (400 MHz, CDCl.sub.3, TMS): 7.97 (d, 2H), 7.88-7.79 (m, 4H), 7.64 (t, 1H), 7.53 (t, 2H), 3.86 (s, 4H), 1.10 (s, 6H) ppm.

Example 9: Ni[P(OR.SUP.1.).SUB.3.][(R.SUP.2.NCH.SUB.2.CH.SUB.2.NR.SUP.2.)C]X.SUB.2 .(R.SUP.1.=CH.SUB.2.CH.SUB.3., R.SUP.2.=2,4,6-trimethylphenyl, X=Br) Catalyzed Cross-Coupling Reaction of p-Cyanochlorobenzene and Bis(Neopentyl Glycolato)-Diboron

(31) Under argon protection, catalyst (6.9 mg, 0.01 mmol, 2 mol %), potassium methoxide (52.6 mg, 0.75 mmol), bis(neopentyl glycolato)-diboron (169.5 mg, 0.75 mmol), p-cyanochlorobenzene (69 mg, 0.50 mmol), 1.5 ml of 1,4-dioxane were sequentially added to the reaction flask, reacted at 40 C. for 6 hours, quenched with water, the reaction product was extracted with ethyl acetate and purified by column chromatography(mixing solvent of ethyl acetate/petroleum ether in a volume ratio of 1:20 as a developing solvent) in a yield of 41%.

(32) The product was dissolved in CDCl.sub.3 (ca. 0.4 mL), sealed, and characterized on a Unity Inova-400 NMR apparatus at room temperature: .sup.1H NMR (400 MHz, CDCl3, TMS): 7.93 (d, 2H), 7.67 (d, 2H), 3.83 (s, 4H), 1.08 (s, 6H) ppm.