Trifluoromethyl alkenylphosphonate and preparation method therefor

Abstract

Disclosed are a trifluoromethyl alkenylphosphonate derivative and preparation method therefor. The preparation method comprises the following steps: dissolving an acetylene derivative, an iodine compound, and a phosphorus reagent in a solvent for reaction at the temperature from the room temperature to 100 C. to obtain the trifluoromethyl alkenylphosphonate derivative. In the present invention, the acetylene derivative is used as a starting material, and the raw materials are easily available and diversified; products obtained by using the method of the present invention have various types and can be directly used and also used for other further reactions; moreover, the method disclosed in the present invention has the advantages of short steps, mild reaction conditions, simple reaction operation and post-treatment processes, and high yield, and is suitable for large-scale production.

Claims

1. A method for preparing a trifluoromethyl alkenylphosphonate derivative comprising: reacting an acetylene derivative, an iodine compound, and a phosphorus reagent in a solvent at room temperature to obtain the trifluoromethyl alkenylphosphonate derivative, wherein: the acetylene derivative has the following structure: ##STR00007## the iodine compound has the following structure: ##STR00008## the phosphorus reagent has the following structure:
P(OR.sup.4).sub.3; the trifluoromethyl alkenylphosphonate derivative has the following structure: ##STR00009## R.sup.1 is aryl, cyano, or ester; R.sup.2 is hydrogen, cyano or ester; and R.sup.4 is methyl, ethyl, isopropyl or butyl.

2. The method according to claim 1, wherein the solvent is the group consisting of acetone, ethyl acetate, toluene, and N, N-dimethylformamide.

3. The method according to claim 1, wherein the acetylene derivative is selected from the group consisting of phenylacetylene, 4-methylphenylacetylene, 4-methoxyphenyl-acetylene, 4-fluorophenylacetylene, 4-chlorophenyl-acetylene, 4-bromophenylacetylene, 4-nitrophenylacetylene, 4-methoxycarbonylphenylacetylene, 4-cyanophenylacetylene, 1-trifluoromethyl-2-cyanoacetylene, 2-ethynylthiophene, 2-bromophenyl-acetylene, and 3-fluorophenyl-acetylene; the phosphorus reagent is selected from the group consisting of trimethyl phosphite, triethyl phosphite, and tri-n-butyl phosphate.

4. The method according to claim 1, further comprising: tracking reaction to completion by a thin layer chromatography.

5. The method according to claim 1, wherein a molar ratio of the acetylene derivative:the iodine compound:the phosphorus reagent is 1:1.5:(3 to 7).

6. The method according to claim 1, wherein the reaction of the acetylene derivative, the iodine compound, and the phosphorus reagent is conducted in the solvent without a catalyst.

Description

EMBODIMENTS OF THE INVENTION

(1) The following further describes the present invention with reference to the embodiments:

(2) In the embodiments, the iodine compound has the following structure:

(3) ##STR00006##

Example 1 Synthesis of (1-phenyl-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(4) Taking phenylacetylene as starting material, the reaction steps were as follow:

(5) (1) Phenylacetylene (20.4 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (99.4 mg, 0.6 mmol) were dissolved in 1 mL of acetone in a reaction flask. The reaction mixture was stirred at 60 C.;

(6) (2) The reaction was tracked to completion by TLC.

(7) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 93%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.54-7.36 (m, 3H), 7.30 (dd, J=6.7, 2.8 Hz, 2H), 6.81 (dq, J=23.0, 7.7 Hz, 1H), 4.27-4.01 (m, 4H), 1.41-1.24 (m, 6H); HRMS (ESI-TOF) m/z: (M+Na): calculated value: 331.0687, measured value: 331.0691.

Example 2 Synthesis of (1-(4-tolyl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(8) Taking 4-methylphenylacetylene as starting material, the reaction steps were as follow:

(9) (1) 4-Methylphenylacetylene (23.2 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (132.8 mg, 0.8 mmol) were dissolved in 1 mL of acetone in a reaction flask. The reaction mixture was stirred at 50 C.;

(10) (2) The reaction was tracked to completion by TLC.

(11) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 87%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.17 (q, J=8.2 Hz, 3H), 6.74 (dq, J=23.0, 7.7 Hz, 1H), 4.18-3.95 (m, 4H), 2.37 (s, 3H), 1.28 (t, J=7.1 Hz, 6H); HRMS (ESI-TOF) m/z: (M+Na): calculated value: 345.0843, measured value: 345.0857.

Example 3 Synthesis of (1-(4-methoxyphenyl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(12) Taking 4-methoxyphenylacetylene as starting material, the reaction steps were as follow:

(13) (1) 4-Methoxyphenylacetylene (26.4 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (166 mg, 1.0 mmol) were dissolved in 1 mL of ethyl acetate in a reaction flask. The reaction mixture was stirred at 40 C.;

(14) (2) The reaction was tracked to completion by TLC.

(15) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 83%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.20 (dd, J=8.7, 1.9 Hz, 2H), 6.90 (t, J=5.5 Hz, 2H), 6.70 (dq, J=23.0, 7.8 Hz, 1H), 4.12-4.02 (m, 4H), 3.81 (s, 3H), 1.27 (t, J=7.1 Hz, 6H); HRMS (ESI-TOF) m/z: (M+H): calculated value: 339.0973, measured value: 339.0984.

Example 4 Synthesis of (1-(4-fluorophenyl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(16) Taking 4-fluorophenylacetylene as starting material, the reaction steps were as follow:

(17) (1) 4-Fluorophenylacetylene (24 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (199.2 mg, 1.2 mmol) were dissolved in 1 mL of ethyl acetate in a reaction flask. The reaction mixture was stirred at room temperature;

(18) (2) The reaction was tracked to completion by TLC.

(19) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 75%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.32-7.20 (m, 2H), 7.07 (dd, J=15.4, 7.0 Hz, 2H), 6.75 (dq, J=22.8, 7.6 Hz, 1H), 4.23-3.99 (m, 4H), 1.28 (t, J=12.3, 6.0 Hz, 6H); HRMS (ESI-TOF) m/z: (M+Na): calculated value: 349.0593, measured value: 349.0600.

Example 5 Synthesis of (1-(4-chlorophenyl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(20) Taking 4-chlorophenylacetylene as starting material, the reaction steps were as follow:

(21) (1) 4-Chlorophenylacetylene (27.2 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (232 mg, 1.4 mmol) were dissolved in 1 mL of ethyl acetate in a reaction flask. The reaction mixture was stirred at 70 C.;

(22) (2) The reaction was tracked to completion by TLC.

(23) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 77%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.37-7.33 (m, 2H), 7.24-7.15 (m, 2H), 6.75 (dq, J=22.9, 7.6 Hz, 1H), 4.13-4.04 (m, 4H), 1.31-1.25 (m, 6H). HRMS (ESI-TOF) m/z: (M+H); HRMS (ESI-TOF) m/z: (M+H): calculated value: 343.0478, measured value: 343.0485.

Example 6 Synthesis of (1-(4-bromophenyl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(24) Taking 4-bromophenylacetylene as starting material, the reaction steps were as follow:

(25) (1) 4-Bromophenylacetylene (36.2 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (99.4 mg, 0.6 mmol) were dissolved in 1 mL of toluene in a reaction flask. The reaction mixture was stirred at 100 C.;

(26) (2) The reaction was tracked to completion by TLC.

(27) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 81%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.50 (d, J=8.2 Hz, 2H), 7.12 (dd, J=8.5, 1.9 Hz, 2H), 6.74 (dq, J=22.9, 7.6 Hz, 1H), 4.12-4.03 (m, 4H), 1.27 (t, J=7.1 Hz, 6H); HRMS (ESI-TOF) m/z: (M+Na): calculated value: 408.9792, measured value: 8.9810.

Example 7 Synthesis of (1-(4-cyanophenyl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(28) Taking 4-cyanophenylacetylene as starting material, the reaction steps were as follow:

(29) (1) 4-Cyanophenylacetylene (25.4 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (166 mg, 1.0 mmol) were dissolved in 1 mL of N, N-dimethylformamide in a reaction flask. The reaction mixture was stirred at room temperature;

(30) (2) The reaction was tracked to completion by TLC.

(31) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 88%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.67 (t, J=7.2 Hz, 2H), 7.37 (dd, J=8.3, 1.7 Hz, 2H), 6.79 (dq, J=22.8, 7.5 Hz, 1H), 4.16-4.07 (m, 4H), 1.29 (t, J=7.1 Hz, 6H); HRMS (ESI-TOF) m/z: (M+Na): calculated value: 356.0639, measured value: 356.0645.

Example 8 Synthesis of (1-(4-nitrophenyl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(32) Taking 4-nitrophenylacetylene as starting material, the reaction steps were as follow:

(33) (1) 4-Nitrophenylacetylene (29.4 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (166 mg, 1.0 mmol) were dissolved in 1 mL of N, N-dimethylformamide in a reaction flask. The reaction mixture was stirred at 90 C.;

(34) (2) The reaction was tracked to completion by TLC.

(35) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 82%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 8.28 (d, J=8.3 Hz, 2H), 7.46 (dd, J=8.7, 1.8 Hz, 2H), 6.85 (dq, J=22.7, 7.5 Hz, 1H), 4.21-4.07 (m, 4H), 1.31 (t, J=7.0 Hz, 6H); HRMS (ESI-TOF) m/z: (M+H): calculated value: 354.0718, measured value: 354.0731.

Example 9 Synthesis of (1-(4-methoxycarbonylphenyl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(36) Taking 4-methoxycarbonylphenylacetylene as starting material, the reaction steps were as follow:

(37) (1) 4-Methoxycarbonylphenylacetylene (32 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (199.2 mg, 1.2 mmol) were dissolved in 1 mL of N, N-dimethylformamide in a reaction flask. The reaction mixture was stirred at 80 C.;

(38) (2) The reaction was tracked to completion by TLC.

(39) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 81%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 8.07 (d, J=8.1 Hz, 2H), 7.35 (dd, J=8.3, 1.7 Hz, 2H), 6.80 (dq, J=22.9, 7.6 Hz, 1H), 4.17-4.03 (m, 4H), 3.94 (s, 3H), 1.29 (t, J=7.1 Hz, 6H); HRMS (ESI-TOF) m/z: (M+H): calculated value: 367.0922, measured value: 367.0935.

Example 10 Synthesis of (1-phenyl-2-trifluoromethyl)dimethylvinylphosphonate

(40) Taking phenylacetylene as starting material, the reaction steps were as follow:

(41) (1) Phenylacetylene (20.4 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (99.4 mg, 0.6 mmol) were dissolved in 1 mL of acetone in a reaction flask. The reaction mixture was stirred at 50 C.;

(42) (2) The reaction was tracked to completion by TLC.

(43) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 81%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.43-7.33 (m, 3H), 7.26 (dd, J=7.8, 4.3 Hz, 2H), 6.79 (dq, J=23.0, 7.6 Hz, 1H), 3.74 (d, J=11.1 Hz, 6H); HRMS (ESI-TOF) m/z: (M+Na): calculated value: 303.0374, measured value: 303.0381.

Example 11 Synthesis of (1-phenyl-2-trifluoromethyl)vinylphosphonic acid dibutyl ester

(44) Taking phenylacetylene as starting material, the reaction steps were as follow:

(45) (1) Phenylacetylene (20.4 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), tri-n-butyl phosphite (300 mg, 1.2 mmol) were dissolved in 1 mL of acetone in a reaction flask. The reaction mixture was stirred at 30 C.;

(46) (2) The reaction was tracked to completion by TLC.

(47) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 71%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.45-7.33 (m, 3H), 7.31-7.19 (m, 2H), 6.76 (dq, J=23.0, 7.7 Hz, 1H), 4.11-3.91 (m, 4H), 1.66-1.51 (m, 4H), 1.40-1.24 (m, 4H), 0.88 (t, J=7.4 Hz, 6H); HRMS (ESI-TOF) m/z: (M+H): calculated value: 365.1493, measured value: 365.1505.

Example 12 Synthesis of (1-cyano-2,2-bis(trifluoromethyl)vinylphosphonic acid diethyl ester

(48) Taking 1-trifluoromethyl-2-cyanoacetylene as starting material, the reaction steps were as follow:

(49) (1) 1-Trifluoromethyl-2-cyanoacetylene (23.6 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (99.4 mg, 0.6 mmol) were dissolved in 1 mL of N, N-dimethylformamide in a reaction flask. The reaction mixture was stirred at 60 C.;

(50) (2) The reaction was tracked to completion by TLC.

(51) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 77%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 4.54-4.30 (m, 4H), 1.22 (t, J=7.4 Hz, 6H); HRMS (ESI-TOF) m/z: (M+H): calculated value: 326.0381, measured value: 326.0392.

Example 13 Synthesis of (1-(thiophen-2-yl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(52) Taking 2-ethynylthiophene as starting material, the reaction steps were as follow:

(53) (1) 2-Ethynylthiophene (21.6 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (99.4 mg, 0.6 mmol) were dissolved in 1 mL of N, N-dimethylformamide in a reaction flask. The reaction mixture was stirred at room temperature;

(54) (2) The reaction was tracked to completion by TLC.

(55) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 84%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.50-7.40 (m, 1H), 7.19 (t, J=2.5 Hz, 1H), 7.06 (dd, J=6.5, 2.2 Hz, 1H), 6.79 (dq, J=22.3, 7.9 Hz, 1H), 4.18-4.07 (m, 4H), 1.30 (t, J=7.1 Hz, 6H); HRMS (ESI-TOF) m/z: (M+Na): calculated value: 337.0251, measured value: 337.0263.

Example 14 Synthesis of (1-(2-bromophenyl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(56) Taking 2-bromophenylacetylene as starting material, the reaction steps were as follow:

(57) (1) 2-Bromophenylacetylene (36 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (199.2 mg, 1.2 mmol) were dissolved in 1 mL of N, N-dimethylformamide in a reaction flask. The reaction mixture was stirred at 40 C.;

(58) (2) The reaction was tracked to completion by TLC.

(59) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 93%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.48-7.43 (m, 1H), 7.36-7.29 (m, 2H), 7.25-7.20 (m, 1H), 6.88 (dq, J=22.6, 7.5 Hz, 1H), 4.23-4.08 (m, 4H), 1.33 (t, J=10.6, 7.0, 0.4 Hz, 6H); HRMS (ESI-TOF) m/z: (M+H): calculated value: 386.9973, measured value: 386.9984.

Example 15 Synthesis of (1-(3-fluorophenyl)-2-trifluoromethyl)vinylphosphonic acid diethyl ester

(60) Taking 3-fluorophenylacetylene as starting material, the reaction steps were as follow:

(61) (1) 3-fluorophenylacetylene (24 mg, 0.2 mmol), the iodine compound (94.8 mg, 0.3 mmol), triethyl phosphite (199.2 mg, 1.2 mmol) were dissolved in 1 mL of N, N-dimethylformamide in a reaction flask. The reaction mixture was stirred at room temperature;

(62) (2) The reaction was tracked to completion by TLC.

(63) (3) After the reaction was complete, the reaction mixture containing a crude product was purified by column chromatography (petroleum ether:acetone=1:8) to obtain the title compound (a yield of 8%). The analytical data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3): 7.34-7.19 (m, 2H), 7.05 (dd, J=15.4, 7.0 Hz, 2H), 6.74 (dq, J=22.8, 7.6 Hz, 1H), 4.22-4.01 (m, 4H), 1.27 (t, J=12.3, 6.0 Hz, 6H); HRMS (ESI-TOF) m/z: (M+Na): calculated value: 349.0593, measured value: 349.0586.