4-SULFUR PENTAFLUORIDE PHENOL COMPOUND AND PREPARATION METHOD THEREFOR, AND PREPARATION METHOD FOR SULFUR PENTAFLUORIDE SUBSTITUTED BENZOPYRAN COMPOUND

Abstract

Provided are a 4-sulfur pentafluoride phenol compound and a preparation method therefor, and a preparation method for a sulfur pentafluoride substituted benzopyran compound. According to the present invention, sulfur pentafluoride salicylaldehyde with multiple substituent groups is synthesized through a plurality of steps by using sulfur pentafluoride phenol as a raw material, and then the sulfur pentafluoride substituted benzopyran compound is synthesized on this basis. The method is simple and convenient, and low in cost; overcomes the defects that, at present, the number of types of sulfur pentafluoride phenols is small, and the synthesis of various sulfur pentafluoride substituted benzopyran compounds cannot be met; and has wide industrial application prospects.

Claims

1-12. (canceled)

13. A 4-sulfur pentafluoride phenol-based compound, wherein the compound has a structure as shown by formula II below: ##STR00059## wherein, R.sub.1 is any one selected from a group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.15 alkylaryl and C.sub.3-C.sub.8 heterocyclic radical.

14. The 4-sulfur pentafluoride phenol-based compound according to claim 13, wherein R.sub.1 is any one selected from a group consisting of C.sub.1-C.sub.8 alkyl, C.sub.6-C.sub.11 alkylaryl and C.sub.4-C.sub.6 heterocyclic radical.

15. The 4-sulfur pentafluoride phenol-based compound according to claim 14, wherein R.sub.1 is any one selected from a group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, phenyl, benzyl, substituted benzyl and ##STR00060##

16. A preparation method for the 4-sulfur pentafluoride phenol-based compound of claim 13, wherein the preparation method comprises the following steps: compound I reacts with sodium borohydride or a Grignard reagent to obtain compound II, as shown by the following reaction formula: ##STR00061## wherein, R.sub.1 is any one selected from a group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.15 alkylaryl and C.sub.3-C.sub.8 heterocyclic radical.

17. The preparation method according to claim 16, wherein compound I is prepared by using 4-sulfur pentafluoride phenol as a raw material, and the preparation method thereof is as follows: 4-sulfur pentafluoride phenol reacts with hexamethylenetetramine in an acid solution to obtain compound I, as shown by the following reaction formula: ##STR00062##

18. The preparation method according to claim 17, wherein the acid solution is any one or a combination of at least two selected from a group consisting of polyphosphoric acid, glacial acetic acid and trifluoroacetic acid, wherein the molar ratio of 4-sulfur pentafluoride phenol to hexamethylenetetramine is from 1:1.2 to 1:2, wherein the acid solution is used in an amount from 5 to 15 mL on the basis of 1 g of 4-sulfur pentafluoride phenol; wherein the temperature at which 4-sulfur pentafluoride phenol and hexamethylenetetramine react in an acid solution is from 70 C. to 90 C.; wherein the time for the reaction between 4-sulfur pentafluoride phenol and hexamethylenetetramine in an acid solution is from 5 to 24 hours.

19. The preparation method according to claim 16, wherein the Grignard reagent has a molecular formula of R.sub.3MgX, R.sub.3 is any one selected from a group consisting of C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.15 alkylaryl and C.sub.3-C.sub.8 heterocyclic radical, and X is a halogen; wherein the molar ratio of compound I to sodium borohydride or the Grignard reagent is from 1:2 to 1:4; wherein the solvent for the reaction between compound I and sodium borohydride or a Grignard reagent is C.sub.1-C.sub.4 alcohol; wherein the solvent is used in an amount from 10 to 20 mL on the basis of 1 g of compound I; wherein the reaction of compound I with sodium borohydride or a Grignard reagent is carried out under a reflux condition; wherein the time for the reaction between compound I and sodium borohydride or a Grignard reagent is from 1 to 5 hours.

20. A 4-sulfur pentafluoride phenol-based compound, wherein the compound has a structure as shown by the formula III(b) below: ##STR00063## wherein, R.sub.1 is any one selected from a group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.15 alkylaryl and C.sub.3-C.sub.8 heterocyclic radical, and R.sub.2 is halogen.

21. The 4-sulfur pentafluoride phenol-based compound according to claim 20, wherein R.sub.1 is any one selected from a group consisting of C.sub.1-C.sub.8 alkyl, C.sub.6-C.sub.11 alkylaryl and C.sub.4-C.sub.6 heterocyclic radical.

22. The 4-sulfur pentafluoride phenol-based compound according to claim 21, wherein R.sub.1 is any one selected from a group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, phenyl, benzyl, substituted benzyl and ##STR00064## and R.sub.2 is selected from a group consisting of F, Br, Cl and I.

23. A preparation method for 4-sulfur pentafluoride phenol-based compound according to claim 20, wherein the method comprises the following steps: compound II reacts with a halogenated reagent to obtain compound III (b), as shown by the following reaction formula: ##STR00065## wherein, R.sub.1 is any one selected from a group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.15 alkylaryl and C.sub.3-C.sub.8 heterocyclic radical, and R.sub.2 is halogen.

24. The preparation method according to claim 20, wherein the halogenated reagent is N-chlorosuccinimide and/or N-bromosuccinimide; wherein the molar ratio of compound II to the halogenated reagent is from 1:2 to 1:4; wherein the reaction temperature is from 60 C. to 100 C.; wherein the reaction time is from 8 to 24 hours.

25. A preparation method for a sulfur pentafluoride substituted benzopyran-based compound, wherein the method comprises the following steps: (1) Compound II reacts with chloroformate, and then reacts with sodium borohydride to obtain compound III (a), as shown by the following reaction formula: ##STR00066## (2) Compound III (a) reacts with hexamethylenetetramine in an acid solution to obtain compound IV, as shown by the following reaction formula: ##STR00067## (3) Compound IV reacts with ethyl 4,4,4-trifluorocrotonate and a weak base in a solvent to obtain compound V, as shown by the following reaction formula: ##STR00068## (4) Compound V is hydrolyzed with a base, and then neutralized with an acid to obtain product VI, as shown by the following reaction formula: ##STR00069## wherein, each of R.sub.1 and R is any one independently selected from a group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.15 alkylaryl and C.sub.3-C.sub.8 heterocyclic radical.

26. The preparation method according to claim 25, wherein the chloroformate in step (1) is any one or a combination of at least two selected from a group consisting of methyl chloroformate, ethyl chloroformate, propyl chloroformate and butyl chloroformate, wherein the molar ratio of compound II to chloroformate in step (1) is from 1:2 to 1:3; wherein the molar ratio of compound II to sodium borohydride in step (1) is from 1:8 to 1:10; wherein the solvent used in the reaction of compound II with chloroformate in step (1) is dichloromethane and/or chloroform; wherein the reaction of compound II with chloroformate in step (1) is carried out in the presence of a weakly basic substance; wherein the molar ratio of compound II to the weakly basic substance is from 1:2 to 1:10; wherein the temperature for the reaction between compound II and chloroformate in step (1) is from 0 C. to 30 C.; wherein the time for the reaction between compound II and chloroformate in step (1) is from 1 to 5 hours; wherein the temperature for the reaction between compound II and sodium borohydride in step (1) is from 0 C. to 30 C.; wherein the time for the reaction between compound II and sodium borohydride in step (1) is from 1 to 5 hours; wherein the acid solution in step (2) is any one or a combination of at least two selected from a group consisting of trifluoroacetic acid, polyphosphoric acid and glacial acetic acid; wherein the molar ratio of compound III(a) to hexamethylenetetramine in step (2) is from 1:1.2 to 1:2; wherein the amount of the acid solution used in step (2) is from 10 to 30 mL on the basis of 1 g of compound III(a); wherein the reaction temperature in step (2) is from 60 C. to 100 C.; wherein the reaction time in step (2) is from 8 to 48 hours; wherein the molar ratio of compound IV to ethyl 4,4,4-trifluorocrotonate in step (3) is from 1:1.2 to 1:10; wherein the weak base in step (3) is any one or a combination of at least two selected from a group consisting of triethylamine, potassium carbonate, cesium carbonate and cesium fluoride; wherein the amount of the weak base used in step (3) is from 10 to 20 mL on the basis of 1 g of compound IV; wherein the solvent used in step (3) is any one or a combination of at least two selected from a group consisting of triethylamine, tetrahydrofuran, N,N-dimethylformamide and dimethyl sulfoxide; wherein the reaction temperature in step (3) is from 80 C. to 120 C.; wherein the reaction time in step (3) is from 10 to 72 hours; wherein the base in step (4) is any one or a combination of at least two selected from a group consisting of potassium hydroxide, sodium hydroxide and lithium hydroxide; wherein the molar ratio of compound V to the base in step (4) is from 1:10 to 1:20; wherein the temperature for the hydrolysis with a base in step (4) is from 20 C. to 30 C.; wherein the time for the hydrolysis with a base in step (4) is from 1 to 5 hours; wherein the acid in step (4) is hydrochloric acid and/or sulfuric acid.

27. The preparation method according to claim 26, wherein the preparation method comprises the following steps: (1) 4-sulfur pentafluoride phenol reacts with hexamethylenetetramine in trifluoroacetic acid to obtain compound I, as shown by the following reaction formula: ##STR00070## (2) Compound I reacts with sodium borohydride or a Grignard reagent to obtain compound II, as shown by the following reaction formula: ##STR00071## (3) Compound II reacts with ethyl chloroformate in the presence of triethylamine, and then reacts with sodium borohydride to obtain compound III (a), as shown by the following reaction formula: ##STR00072## (4) Compound III (a) reacts with hexamethylenetetramine in trifluoroacetic acid to obtain compound IV, as shown by the following reaction formula: ##STR00073## (5) Compound IV reacts with ethyl 4,4,4-trifluorocrotonate and triethylamine in a solvent to obtain compound V, as shown by the following reaction formula: ##STR00074## (6) Compound V is hydrolyzed with a base, and then neutralized with an acid to obtain product VI, as shown by the following reaction formula: ##STR00075## wherein, each of R.sub.1 and R is any one independently selected from a group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.15 alkylaryl and C.sub.3-Cs heterocyclic radical.

28. The preparation method according to claim 27, wherein product VI is a racemate compound, and in order to obtain a chiral compound thereof, a chiral catalyst is added to the reaction of compound IV with ethyl 4,4,4-trifluorocrotonate.

29. The preparation method according to claim 28, wherein the chiral catalyst is a diphenylprolinol silyl ether-based compound or a dinaphthylprolinol silyl ether-based compound, wherein the molar ratio of the chiral catalyst to compound IV is from 1:4 to 1:6.

30. A preparation method for a sulfur pentafluoride substituted benzopyran-based compound, wherein the preparation method comprises the following steps: A. compound III (b) reacts with an oxidant to obtain compound IV (b), as shown by the following reaction formula: ##STR00076## B. Compound IV (b) reacts with ethyl 4,4,4-trifluorocrotonate and a weak base in a solvent to obtain compound V(b), as shown by the following reaction formula: ##STR00077## C. Compound V (b) is hydrolyzed with a base, and then neutralized with an acid to obtain the product VI (b), as shown by the following reaction formula: ##STR00078## wherein, R.sub.1 is any one selected from a group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.15 alkylaryl and C.sub.3-C.sub.8 heterocyclic radical, and R.sub.2 is halogen.

31. The preparation method according to claim 30, wherein: the oxidant in step A is pyridinium chlorochromate and/or manganese dioxide; the molar ratio of compound III (b) to the oxidant in step A is from 1:2 to 1:20; the reaction temperature in step A is from 10 C. to 30 C.; the reaction time in step A is from 5 to 24 hours; the molar ratio of compound IV (b) to ethyl 4,4,4-trifluorocrotonate in step B is from 1:1.2 to 1:10; the weak base in step B is any one or a combination of at least two selected from a group consisting of triethylamine, potassium carbonate, cesium carbonate and cesium fluoride; the amount of the weak base used in step B is from 10 to 20 mL on the basis of 1 g of compound IV(b); the solvent in step B is any one or a combination of at least two selected from a group consisting of triethylamine, tetrahydrofuran, N,N-dimethylformamide and dimethyl sulfoxide; the reaction temperature in step B is from 80 C. to 120 C.; the reaction time in step B is from 10 to 72 hours; the base in step C is any one or a combination of at least two selected from a group consisting of potassium hydroxide, sodium hydroxide and lithium hydroxide; the molar ratio of compound V(b) to the base in step C is from 1:10 to 1:20; the temperature for the hydrolysis with a base in step C is from 20 C. to 30 C.; the time for the hydrolysis with a base in step C is from 1 to 5 hours; the acid in step C is hydrochloric acid and/or sulfuric acid.

32. The preparation method according to claim 30, wherein the method comprises the following steps: (1) 4-sulfur pentafluoride phenol reacts with hexamethylenetetramine in an acid solution to obtain compound I, as shown by the following reaction formula: ##STR00079## (2) compound I reacts with sodium borohydride or a Grignard reagent to obtain compound II, as shown by the following reaction formula: ##STR00080## (3) Compound II reacts with a halogenated reagent to obtain compound III (b), as shown by the following reaction formula: ##STR00081## (4) compound III(b) reacts with an oxidant to obtain compound IV(b), as shown by the following reaction formula: ##STR00082## (5) Compound IV(b) reacts with ethyl 4,4,4-trifluorocrotonate and a weak base in a solvent to obtain compound V, as shown by the following reaction formula: ##STR00083## (6) Compound V (b) is hydrolyzed with a base, and then neutralized with an acid to obtain product VI (b), as shown by the following reaction formula: ##STR00084## wherein, R.sub.1 is any one selected from a group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.6-C.sub.15 alkylaryl and C.sub.3-C.sub.8 heterocyclic radical, and R.sub.2 is halogen.

Description

DETAILED DESCRIPTION

[0117] The technical solutions of the present disclosure will be further described below by way of specific embodiments. It will be apparent to those skilled in the art that the embodiments are merely illustrations of the present disclosure and should not be construed as specific limitations to the present disclosure.

Example 1

Synthesis of 6-sulfur pentafluoride-8-methyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid

[0118] The synthetic route is as follows:

##STR00032##

[0119] (1) Synthesis of 5-sulfur pentafluoride-2-hydroxybenzaldehyde

##STR00033##

[0120] Under protection of argon, p-sulfur pentafluoride phenol (1.0 g, 4.5 mmol) was dissolved in trifluoroacetic acid (6 mL), and then hexamethylenetetramine (1.0 g, 7.1 mmol) was slowly added to the above solution, the reaction was maintained at a temperature of 80 C. for 12 h, the reaction solution was cooled to room temperature, to which 6 mL of hydrochloric acid (3 mol/L) was added and then stirred for another 0.5 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate, and the resulting organic phase was washed with brine, dried, and rotary evaporated under reduced pressure, then purified through column chromatography to give the product (0.53 g, 47%).

[0121] .sup.1H NMR (400 MHz,CDCl.sub.3) 11.31 (s, 1H), 9.94 (s, 1H), 7.99 (d, J=2.7 Hz, 1H), 7.90 (dd, J=9.2, 2.7 Hz, 1H), 7.02 (dd, J=35.3, 11.0 Hz, 1H). MS (MMES+APCI), m/z: 247.0(MH.sup.+).

[0122] (2) Synthesis of 4-sulfur pentafluoride-2-hydroxymethylphenol

##STR00034##

[0123] 5-sulfur pentafluoride-2-hydroxybenzaldehyde (0.40 g, 1.61 mmol) and ethanol (6 mL) were added to a single-necked flask, to which solid sodium borohydride (0.080 g, 2.2 mmol) was slowly added, the mixture was heated to reflux for 2 h, then cooled to room temperature and adjusted to a pH of less than 3 with hydrochloric acid (3 mol/L), which was then extracted three times with dichloromethane (20 mL), the resulting organic phase was washed with brine, dried over anhydrous sodium sulfate for 15 minutes and directly used for the next reaction.

[0124] .sup.1NMR (400 MHz, CDCl.sub.3) 10.559 (s, 1H), 7.75 (s, 1H), 7.57 (d, J=8 Hz, 1H), 6.88 (dd, J=8 Hz, 1H), 4.49 (s, 2H).

[0125] (3) Synthesis of 4-sulfur pentafluoride-2-methylphenol

##STR00035##

[0126] Under protection of argon, the dichloromethane solution containing crude product (theoretical value 0.40 g, 1.61 mmol) obtained in step 2 was cooled in an ice bath, to which triethylamine (9.6 mmol, 1.05 g) was added, subsequently ethyl chloroformate (0.52 g, 4.80 mmol) was added dropwise, the mixture was stirred for 30 minutes, then warmed to room temperature and stirred for 1.5 h. At the end of the reaction, the solvent was distilled off under reduced pressure to give a solid residue, which was dissolved in ethanol (3 mL), and slowly added dropwise to an aqueous solution (5 mL) of sodium borohydride (1.5 g, 38.4 mmol) in ice bath, then the mixture was stirred for 0.5 h, and warmed to room temperature and stirred for 1.5 h.

[0127] After the reaction was completed, the mixture was adjusted to a pH of less than 3 by carefully adding dropwise dilute hydrochloric acid (3 mol/L) in ice bath, then extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure, the crude product was isolated by column chromatography to give the product (0.30 g, 1.3 mmol, 80%).

[0128] .sup.1H NMR (400 MHz, CDCl.sub.3) 7.53 (t, J=5.8 Hz, 1H), 7.46 (dd, J=8.8, 2.7 Hz, 1H), 6.79 (d, J=8.8 Hz, 1H), 2.28 (s, 3H). MS (MMES+APCI), m/z: 233 (MH.sup.+). (4) Synthesis of 5-sulfur pentafluoride-2-hydroxy-3-methylbenzaldehyde

##STR00036##

[0129] Under protection of argon, the resulting product 4-sulfur pentafluoride-2-methylphenol (0.30 g, 1.3 mmol) obtained in step 3 was dissolved in trifluoroacetic acid (6 mL), and then hexamethylenetetramine (0.31 g, 2.22 mmol) was slowly added to the above solution, the reaction was maintained at a temperature of 80 C. for 12 h, and then the reaction solution was cooled to room temperature, to which 3 mL of hydrochloric acid (3 mol/L) was added and then stirred for another 0.5 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate, and the resulting organic phase was washed with brine, dried, and rotary evaporated under reduced pressure, then purified through column chromatography to give the product (0.16 g, 0.61 mmol, 47%).

[0130] .sup.1H NMR (400 MHz, CDCl.sub.3) 11.56 (s, 1H), 9.91 (s, 1H), 7.83 (d, J=2.5 Hz, 1H), 7.76 (s, 1H), 2.33 (s, 3H).

[0131] MS (MMES+APCI), m/z: 261.0(MH.sup.+).

[0132] (5) Synthesis of Ethyl 6-sulfur pentafluoride-8-methyl-2-trifluoromethyl-2H-benzopyran-3-carboxylate

##STR00037##

[0133] 5-sulfur pentafluoride-2-hydroxy-3-methylbenzaldehyde (0.16 g, 0.61 mmol), ethyl 4,4,4-trifluorocrotonate (0.50 g, 3.0 mmol), and triethylamine (2 mL) were dissolved in DMF (5 ml), then stirred in a sealed tube at 110 C. for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature and adjusted to a pH of less than 3 with hydrochloric acid (3 mol/L), then extracted with ethyl acetate, and the resulting organic phase was dried, and rotary evaporated under reduced pressure, then purified through column chromatography to give the product (0.12 g, 0.29 mmol, 48%).

[0134] .sup.1H NMR (400 MHz, CDCl.sub.3) 7.70 (s, 1H), 7.56 (d, J=2.3 Hz, 1H), 7.48 (d, J=2.5 Hz, 1H), 5.81 (q, J=6.7 Hz, 1H), 4.41-4.26 (m, 2H), 2.31 (s, 3H), 1.35 (dd, J=12.6, 5.4 Hz, 3H).

[0135] MS (MMES+APCI), m/z: 411(MH.sup.+).

[0136] (6) Synthesis of 6-sulfur pentafluoride-8-methyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid

##STR00038##

[0137] The product obtained in step 5 (0.12 g, 0.29 mmol), potassium hydroxide (0.16 g, 2.9 mmol), ethanol (3 ml), and water (1 ml) were added in sequence to a single-necked flask. The mixture was stirred at room temperature for 3 h, the pH was adjusted to less than 3 after the completion of the reaction, which was then extracted with ethyl acetate, washed with saturated sodium chloride aqueous solution, dried and rotary evaporated under reduced pressure to give the product (0.10 g, 0.26 mmol, 90%).

[0138] .sup.1H NMR (400 MHz, CDCl.sub.3) 7.81 (s, 1H), 7.60 (d, J=2.1 Hz, 1H), 7.51 (d, J=2.5 Hz, 1H), 5.80 (q, J=6.6 Hz, 1H), 2.31 (s, 3H).

[0139] MS (MMES+APCI), m/z: 383.0(MH.sup.+).

Example 2

Synthesis of 6-sulfur pentafluoride-8-ethyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid

[0140] The synthetic route is as follows:

##STR00039##

[0141] (1) Synthesis of 5-sulfur pentafluoride-2-hydroxybenzaldehyde

##STR00040##

[0142] The p-sulfur pentafluoride phenol (1.0 g, 4.5 mmol) was dissolved in trifluoroacetic acid (6 mL), and then hexamethylenetetramine (1.0 g, 7.1 mmol) was slowly added to the above solution, the reaction was maintained at a temperature of 80 C. for 12 h, the reaction solution was cooled to room temperature, to which 6 mL of hydrochloric acid (3 mol/L) was added and then stirred for another 0.5 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate, and the resulting organic phase was washed with brine, dried, and rotary evaporated under reduced pressure, then purified through column chromatography to give the product (0.53 g, 2.4 mmol, 47%).

[0143] .sup.1H NMR (400 MHz,CDCl.sub.3) 11.31 (s, 1H), 9.94 (s, 1H), 7.99 (d, J=2.7 Hz, 1H), 7.90 (dd, J=9.2, 2.7 Hz, 1H), 7.02 (dd, J=35.3, 11.0 Hz, 1H).

[0144] MS (MMES+APCI), m/z: 247.0(MH.sup.+).

[0145] (2) Synthesis of 4-sulfur pentafluoride-2-(1-hydroxyethyl)phenol

##STR00041##

[0146] Under protection of argon, 5-sulfur pentafluoride-2-hydroxybenzaldehyde (0.53 g, 2.4 mmol), and dry tetrahydrofuran (6 mL) were added to a two-necked flask, methyl magnesium bromide (3.7 mL, 4.8 mmol, 1.3 mol/L solution) was slowly added at room temperature, and the reaction was stirred overnight. After the reaction was completed, the reaction mixture was adjusted to a pH of less than 3 with hydrochloric acid (3 mol/L), and extracted three times with ethyl acetate (20 mL), the organic phase was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to give the product (0.52 g, 2.0 mmol, 81%).

[0147] .sup.1NMR (400 MHz,CDCl.sub.3) 8.60 (s, 1H), 7.56 (dd, J=8.9, 2.6 Hz, 1H), 7.38 (d, J=2.5 Hz, 1H), 6.89 (d, J=9.0 Hz, 1H), 5.12 (q, J=6.5 Hz, 1H), 1.61 (d, J=6.6 Hz, 3H). MS (MMES+APCI), m/z: 263.0(MH.sup.+).

[0148] (3) Synthesis of 4-sulfur pentafluoride-2-ethylphenol

##STR00042##

[0149] Under protection of argon, the product (0.52 g, 2.0 mmol) obtained in step 2 was dissolved in dichloromethane (5 mL), the solution was cooled in an ice bath, to which triethylamine (12 mmol, 12.20 g) was added, subsequently ethyl chloroformate (0.65 g, 6 mmol) was added dropwise, the mixture was stirred for 30 minutes, then warmed to room temperature and stirred for 3 h. At the end of the reaction, the solvent was distilled off under reduced pressure to give a solid residue, which was dissolved in ethanol (10 mL), and slowly added dropwise to an aqueous solution (20 mL) of sodium borohydride (1.82 g, 48 mmol), then the mixture was stirred for 0.5 h, and warmed to room temperature and stirred overnight.

[0150] After the reaction was completed, the mixture was adjusted to a pH of less than 3 by carefully adding dropwise dilute hydrochloric acid (3 mol/L) in an ice bath, then extracted with dichloromethane, the organic phase was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure, the crude product was directly used for the next reaction.

[0151] MS (MMES+APCI), m/z: 247.0(MH.sup.+).

[0152] (4) Synthesis of 5-sulfur pentafluoride-2-hydroxy-3-ethylbenzaldehyde

##STR00043##

[0153] Under protection of argon, the crude product 4-sulfur pentafluoride-2-ethyl-phenol (Theoretical content 0.48 g, 2.0 mmol) obtained in step 3 was dissolved in trifluoroacetic acid (6 mL), and then hexamethylenetetramine (0.440 g, 3.14 mmol) was slowly added to the above solution, the reaction was maintained at a temperature of 80 C. for 12 h, the reaction solution was cooled to room temperature, to which 12 mL of hydrochloric acid (3 mol/L) was added and then stirred for another 0.5 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate, and the resulting organic phase was washed with brine, dried, and rotary evaporated under reduced pressure, then purified through column chromatography to give the product (0.160 g, 0.56 mmol, 28%).

[0154] .sup.1NMR (400 MHz, CDCl.sub.3) 11.58 (s, 1H), 9.91 (s, 1H), 7.83 (d, J=2.7 Hz, 1H), 7.76 (d, J=2.6 Hz, 1H), 2.75 (q, J=7.5 Hz, 2H), 1.30-1.22 (m,3H). MS (MMES+APCI), m/z: 275.0(MH.sup.+).

[0155] (.sup.5) Synthesis of Ethyl 6-sulfur pentafluoride-8-ethyl-2-trifluoromethyl-2H-benzopyran-3-carboxylate

##STR00044##

[0156] 5-sulfur pentafluoride-2-hydroxy-3-ethylbenzaldehyde (0.160 g, 0.56 mmol), ethyl 4,4,4-trifluorocrotonate (0.47 g, 2.80 mmol), and triethylamine (2 mL) were dissolved in DMF (5 ml), then stirred in a sealed tube at 110 C. overnight. After the reaction was completed, the reaction solution was cooled to room temperature and adjusted to a pH of less than 3 with hydrochloric acid (3 mol/L), then extracted with ethyl acetate, and the resulting organic phase was dried, and rotary evaporated under reduced pressure, then purified through column chromatography to give the product (0.12 g, 0.28 mmol, 50%).

[0157] .sup.1H NMR (400 MHz, CDCl.sub.3) 7.70 (s, 1H), 7.56 (d, J=2.6 Hz, 1H), 7.49 (d, J=2.6 Hz, 1H), 5.82 (q, J=6.7 Hz, 1H), 4.40-4.26 (m, 2H), 2.81-2.58 (m, 2H), 1.36 (t, J=7.1 Hz, 3H), 1.28-1.18 (t, J=7.2 Hz, 3H). MS (MMES+APCI), m/z: 425.0(MH.sup.+).

[0158] (6) Synthesis of 6-sulfur pentafluoride-8-ethyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid

##STR00045##

[0159] The product obtained in step 5 (0.12 g, 0.28 mmol), potassium hydroxide (0.16 g, 2.8 mmol), ethanol (12 ml), and water (4 ml) were added in sequence to a single-necked flask. The mixture was stirred at room temperature for 3 h, the pH was adjusted to less than 3 after the completion of the reaction, which was then extracted with ethyl acetate, washed with saturated sodium chloride aqueous solution, dried and rotary evaporated under reduced pressure to give the product (0.080 g, 0.20 mmol, 70%).

[0160] .sup.1H NMR (400 MHz, CDCl.sub.3) 7.82 (s, 1H), 7.60 (d, J=2.6 Hz, 1H), 7.52 (d, J=2.5 Hz, 1H), 5.80 (q, J=6.6 Hz, 1H), 2.71 (ddd, J=30.8, 14.5, 7.3 Hz, 2H), 1.36-1.17 (m, 3H). MS (MMES+APCI), m/z: 397.0(MH.sup.+).

Example 3

Synthesis of 6-sulfur pentafluoride-8-propyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid

[0161] The synthesis method in this Example differs from that in Example 2 only in that the Grignard reagent used in step (2) is ethyl magnesium bromide, which is used in a molar ratio of 4:1 to 5-sulfur pentafluoride-2-hydroxybenzaldehyde. In addition, the preparation methods and conditions are the same as those in Example 2, and by characterization via 1H NMR spectroscopy and mass spectrometry, 6-sulfur pentafluoride-8-propyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid is determined to have the following structure:

##STR00046##

[0162] The characterization results of 1H NMR spectroscopy and mass spectrometry are as follows: .sup.1H NMR (400 MHz, CDCl.sub.3) 7.82 (s, 1H), 7.58 (d, J=2.6 Hz, 1H), 7.51 (s, J=2.6 Hz, 1H), 5.79 (q, J=6.7 Hz, 1H), 2.78-2.54 (m, 2H), 1.71-1.57 (m, 2H), 0.97 (t, J=7.4 Hz, 3H). MS (MMES+APCI), m/z: 411.0(MH.sup.).

Example 4

Synthesis of 6-sulfur pentafluoride-8-butyl-2-(trifluoromethyl)-2H-benzopyran-3-carboxylic acid

[0163] The synthesis method in this Example differs from that in Example 2 only in that the Grignard reagent used in step (2) is propyl magnesium bromide, which is used in a molar ratio of 4:1 to 5-sulfur pentafluoride-2-hydroxybenzaldehyde. In addition, the preparation methods and conditions are the same as those in Example 2, and by characterization via 1H NMR spectroscopy and mass spectrometry, the product is determined to have the following structure:

##STR00047##

[0164] .sup.1H NMR (400 MHz, CDCl.sub.3) 7.83 (s, 1H), 7.58 (d, J=2.2 Hz, 1H), 7.51 (d, J=2.2 Hz, 1H), 5.80 (q, J=6.7 Hz, 1H), 2.80-2.55 (m, 2H), 1.59 (dt, J=15.6, 7.7 Hz, 2H), 1.38 (dq, J=14.7, 7.3 Hz, 2H), 0.95 (t, J=7.3 Hz, 3H). MS (MMES+APCI), m/z: 425.0(MH.sup.+).

Example 5

Synthesis of 6-sulfur pentafluoride-8-pentyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid

[0165] The synthesis method in this Example differs from that in Example 2 only in that the Grignard reagent used in step (2) is butyl magnesium bromide, which is used in a molar ratio of 3:1 to 5-sulfur pentafluoride-2-hydroxybenzaldehyde. In addition, the preparation methods and conditions are the same as those in Example 2, and by characterization via 1H NMR spectroscopy and mass spectrometry, 6-sulfur pentafluoride-8-pentyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid is determined to have the following structure:

##STR00048##

[0166] The characterization results of 1H NMR spectroscopy and mass spectrometry are as follows: .sup.1H NMR (400 MHz, CDCl.sub.3) 7.71 (s, 1H), 7.58 (d, J=2.4 Hz, 1H), 7.55-7.49 (m, 1H), 5.62 (t, J=6.9 Hz, 1H), 3.95-3.82 (m, 2H), 2.78-2.65 (m, 2H), 1.61 (dd, J=14.9, 7.5 Hz, 2H), 1.41-1.29 (m, 2H), 1.15 (t, J=7.1 Hz, 3H). MS (MMES+APCI), m/z: 439.0(MH.sup.+).

Example 6

Synthesis of 6-sulfur pentafluoride-8-benzyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid

[0167] The synthesis method in this Example differs from that in Example 2 only in that the Grignard reagent used in step (2) is phenyl magnesium bromide, which is used in a molar ratio of 2:1 to 5-sulfur pentafluoride-2-hydroxybenzaldehyde. In addition, the preparation methods and conditions are the same as those in Example 2, and by characterization via 1H NMR spectroscopy and mass spectrometry, 6-sulfur pentafluoride-8-benzyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid is determined to have the following structure:

##STR00049##

[0168] The characterization results of 1H NMR spectroscopy and mass spectrometry are as follows: .sup.1H NMR (400 MHz, CDCl.sub.3) 7.83 (s, 1H), 7.56 (s, 2H), 7.31 (t, J=7.3 Hz, 2H), 7.23 (d, J=7.4 Hz, 1H), 7.18 (d, J=7.1 Hz, 2H), 5.79 (q, J=6.6 Hz, 1H), 4.03 (d, J=3.7 Hz, 2H). MS (MMES+APCI), m/z: 459.0(MH+).

Example 7

Synthesis of 6-sulfur pentafluoride-8-(3-methyl-2-pyridylmethylene)-2-trifluoromethyl-2H-benzopyra n-3-carboxylic acid

[0169] The synthesis method in this Example differs from that in Example 2 only in that the Grignard reagent used in step (2) is 3-methyl-2-pyridyl magnesium bromide, which is used in a molar ratio of 2:1 to 5-sulfur pentafluoride-2-hydroxybenzaldehyde. In addition, the preparation methods and conditions are the same as those in Example 2, and by characterization via mass spectrometry, 6-sulfur pentafluoride-8-benzyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid is determined to have the following structure:

##STR00050##

m/z: 475.0(MH+).

Example 8

Synthesis of (S)-6-sulfur pentafluoride-8-chloro-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid

[0170] The synthetic route is as follows:

##STR00051##

[0171] (1) Synthesis of 5-sulfur pentafluoride-2-hydroxybenzaldehyde

##STR00052##

[0172] Under protection of argon, the p-sulfur pentafluoride phenol (1.0 g, 4.5 mmol) was dissolved in trifluoroacetic acid (6 mL), and then hexamethylenetetramine (1.0 g, 7.1 mmol) was slowly added to the above solution, the reaction was maintained at a temperature of 80 C. for 12 h, the reaction solution was cooled to room temperature, to which 6 mL of hydrochloric acid (3 mol/L) was added and then stirred for another 0.5 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate, and the resulting organic phase was washed with brine, dried, and rotary evaporated under reduced pressure, then purified through column chromatography to give the product (0.53 g, 47%).

[0173] .sup.1H NMR (400 MHz,CDCl.sub.3) 11.31 (s, 1H), 9.94 (s, 1H), 7.99 (d, J=2.7 Hz, 1H), 7.90 (dd, J=9.2, 2.7 Hz, 1H), 7.02 (dd, J=35.3, 11.0 Hz, 1H). MS (MMES+APCI), m/z: 247.0(MH.sup.+).

[0174] (2) Synthesis of 4-sulfur pentafluoride-2-hydroxymethyl-phenol

##STR00053##

[0175] 5-sulfur pentafluoride-2-hydroxybenzaldehyde (0.40 g, 1.61 mmol) and ethanol (6 mL) were added to a single-necked flask, to which solid sodium borohydride (0.080 g, 2.2 mmol) was slowly added, the mixture was heated to reflux for 2 h, then cooled to room temperature and adjusted to a pH of less than 3 with hydrochloric acid (3 mol/L), which was then extracted three times with dichloromethane (20 mL), the resulting organic phase was washed with brine, dried over anhydrous sodium sulfate for 15 minutes, rotary evaporated under reduced pressure, then purified through column chromatography to give the product (0.38 g, 94%).

[0176] .sup.1NMR (400 MHz, CDCl.sub.3) 7.92 (s, 1H), 7.61 (d, J=9.0, 2.6 Hz, 1H), 6.92 (d, J=8.9 Hz, 1H), 4.94 (s, 2H). MS (MMES+APCI), m/z: 249.0(MH.sup.+).

[0177] (3) Synthesis of 4-sulfur pentafluoride-2-hydroxymethyl-6-chlorophenol

##STR00054##

[0178] Under protection of argon, 4-sulfur pentafluoride-2-hydroxymethyl-phenol (0.38 g, 1.51 mmol), chlorosuccinimide (i.e., NCS, 0.40 g, 3.03 mmol), p-toluenesulfonic acid monohydrate (i.e., TsOH.Math.H.sub.2O, 0.58 g, 3.03 mmol), sodium chloride (0.26 g, 4.53 mmol) and saturated sodium chloride aqueous solution (2 mL) were mixed in the sealed tube, which was then sealed. The reaction system was stirred and heated at 60 C. overnight. After the reaction was completed, the reaction system was diluted with water (10 mL), and then extracted three times with ethyl acetate (10 mL), the organic phases were combined and washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure, the crude product was isolated by column chromatography to give the product (0.15 g, 35.2%).

[0179] .sup.1NMR (400 MHz, CDCl.sub.3) 7.70 (dd, J=14.3, 3.0 Hz, 1H), 7.54 (dd, J=8.3, 2.6 Hz, 1H), 4.86 (s, 2H). MS (MMES+APCI), m/z: 283.0(MH.sup.+).

[0180] (4) Synthesis of 5-sulfur pentafluoride-2-hydroxy-3-chlorobenzaldehyde

##STR00055##

[0181] 4-sulfur pentafluoride-2-hydroxymethyl-6-chlorophenol (0.15 g, 0.53 mmol), pyridinium chlorochromate (i.e., PCC, 0.23 g, 1.06 mmol) and dichloromethane (10 mL) were mixed and then stirred at room temperature overnight. After the reaction was completed, the solvent was distilled off under reduced pressure, the crude product was isolated by column chromatography to give the product (0.12 g, 80%).

[0182] .sup.1H NMR (400 MHz, CDCl.sub.3) 11.81 (s, 1H), 9.94 (s, 1H), 7.72 (dd, J=8.5, 4.1 Hz, 1H), 7.57-7.50 (dd,J=8.2, 2.7 Hz, 1H). MS (MMES+APCI), m/z: 281.0(MH.sup.+).

[0183] (5) Synthesis of (S)-6-sulfur pentafluoride-8-chloro-2-trifluoromethyl-2H-benzopyran-3-formaldehyde

##STR00056##

[0184] The compound 5-sulfur pentafluoride-2-hydroxy-3-chlorobenzaldehyde (0.12 g, 0.42 mmol), 4,4,4-trifluorobut-2-enal (0.10 g, 0.82 mmol), (2S)-2-[diphenyl[(trimethylsilyl)oxy]methyl]-pyrrolidine (0.026 g, 0.08 mmol), and p-nitrobenzoic acid (0.014 g, 0.08 mmol) were mixed in 50 mL ethyl acetate, then stirred overnight. After the reaction was completed, the crude product was isolated by column chromatography to give the product (0.046 g, yield 28%).

[0185] .sup.1NMR (400 MHz, CDCl.sub.3) 9.72 (s, 1H), 8.02 (s, 1H), 7.94 (s, 1H), 7.64 (s, 1H), 5.89 (q, J=6.6 Hz, 1H). MS (MMES+APCI), m/z: 387.0(MH.sup.+).

[0186] (6) Synthesis of (S)-6-sulfur pentafluoride-8-chloro-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid

##STR00057##

[0187] The compound (S)-6-sulfur pentafluoride-8-chloro-2-trifluoromethyl-2H-benzopyran-3-formaldehyde (0.046 g, 0.12 mmol), and potassium peroxymonosulfate complex salt (0.11 g, 0.18 mmol) were mixed in DMF (5 mL), and the mixture was stirred overnight. After the reaction was completed, water was added to the reaction system and the reaction system was extracted with ethyl acetate, the resulting organic phase was washed with saturated sodium chloride aqueous solution, dried, and rotary evaporated under reduced pressure, then purified through column chromatography to give the product (0.036 g, 75%). After analysis via chiral AD column, its EE value was higher than 92%.

[0188] .sup.1H NMR (400 MHz, CDCl.sub.3) 8.10 (s, 1H), 7.98 (s, 1H), 7.71 (s, 1H), 5.88 (q, J=6.7 Hz, 1H). MS (MMES+APCI), m/z: 403.0(MH.sup.+).

Example 9

Synthesis of (S)-6-sulfur pentafluoride-8-methyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid

[0189] The synthesis method in this Example differs from that in Example 1 only in that the chiral catalyst used in the reaction of step (5) is 2-[diphenyl[(trimethylsilyl)oxy]methyl]-pyrrolidine, which is used in a molar ratio of 4:1 to 5-sulfur pentafluoride-2-hydroxy-3-methylbenzaldehyde. In addition, the preparation methods and conditions are the same as those in Example 1, and by characterization via 1H NMR spectroscopy and mass spectrometry, (S)-6-sulfur pentafluoride-8-methyl-2-trifluoromethyl-2H-benzopyran-3-carboxylic acid is determined to have the following structure:

##STR00058##

[0190] .sup.1H NMR (400 MHz, CDCl.sub.3) 7.63 (s, 1H), 7.56 (s, 1H), 7.54 (s, 1H), 5.81 (q, J=6.7 Hz, 1H), 2.32 (s, 3H). After analysis via chiral AD column, its EE value was higher than 92%.

[0191] Applicant has stated that although the detailed methods of the present disclosure have been described by the above Examples, the present disclosure is not limited thereto, that is to say, it is not meant that the present disclosure has to be implemented depending on the above detailed methods. It will be apparent to those skilled in the art that any improvements made to the present disclosure, equivalent replacements and addition of adjuvant ingredients to the raw materials of the products of the present disclosure, and selections of the specific implementations, etc., all fall within the protection scope and the disclosed scope of the present disclosure.