METHOD FOR PREPARING PYRIDINE COMPOUND SUBSTITUTED WITH TRIFLUOROMETHYLTHIO, DIFLUOROMETHYLTHIO OR TRIFLUOROMETHYL IN META POSITION

Abstract

A method for preparing a pyridine compound substituted with trifluoromethylthio, difluoromethylthio or trifluoromethyl in the meta position is provided, which includes S1. in a glove box filled with nitrogen, adding a catalyst, a solvent, pinacolborane, and pyridine to a reaction flask, stirring the mixture, and performing a reaction at 40-100° C. for 2-12 hours to obtain dihydropyridine; S2. adding a trifluoromethylthio reagent, a difluoromethylthio reagent, or a trifluoromethyl reagent to the reaction flask, stirring the mixture, and performing a reaction at room temperature to 80° C. for 2-12 hours to obtain trifluoromethylthio-, difluoromethylthio- or trifluoromethyl-substituted dihydropyridine; and S3. placing the reaction flask in the air or adding 2,3-dichloro-5,6-dicyanobenzoquinone, stirring same, and performing a reaction at room temperature for 4-12 hours, followed by distillation under reduced pressure to remove the solvent and column chromatography separation to obtain the meta-substituted pyridine compound.

Claims

1. A method for preparing a pyridine compound substituted with trifluoromethylthio, difluoromethylthio, or trifluoromethyl in a meta position, comprising the following steps: S1. a preparation of 1,4-dihydropyridine or 1,2-dihydropyridine: in a glove box filled with nitrogen, adding a catalyst, a solvent, pinacolborane, and pyridine to a reaction flask to obtain a first mixture, and stirring the first mixture for a first reaction to obtain dihydropyridine, with a reaction formula being as follows: ##STR00043## wherein: the catalyst is triarylboron, a molar ratio of the triarylboron to the pyridine is (5-10): 100, and a structural formula of the triarylboron is B(R.sup.4).sub.3 in which R.sup.4 is phenyl, pentafluorophenyl, 3,5-bis(trifluoromethyl)-substituted phenyl, or 2,4,6-trifluoro-substituted phenyl; an equivalent ratio of the pinacolborane to the pyridine is 1.1:1; the solvent is tetrahydrofuran, dichloromethane, dioxane, 1,2-dichloroethane, or an aromatic solvent; and a reaction temperature is 40-100° C. and a reaction time is 2-12 hours; S2. an electrophilic substitution reaction of the dihydropyridine: adding a trifluoromethylthio reagent, a difluoromethylthio reagent, or a trifluoromethyl reagent to the reaction flask to obtain a second mixture, and stirring the second mixture for a second reaction in a nitrogen atmosphere until the second reaction is complete to obtain dihydropyridine substituted with the trifluoromethylthio, the difluoromethylthio, or the trifluoromethyl in the meta position, with a reaction formula being as follows: ##STR00044## wherein a reaction temperature is room temperature to 80° C., and a reaction time is 2 to 12 hours; and S3. an oxidative aromatization to obtain the pyridine compound substituted with the trifluoromethylthio, the difluoromethylthio, or the trifluoromethyl in the meta position: placing the reaction flask in an air or adding 2,3-dichloro-5,6-dicyanobenzoquinone to allow a third reaction, stirring until the third reaction is complete, performing a distillation under a reduced pressure to remove the solvent, and then performing a column chromatography separation to obtain the pyridine compound substituted with the trifluoromethylthio, the difluoromethylthio, or the trifluoromethyl in the meta position, with a reaction formula being as follows: ##STR00045## wherein: an equivalent ratio of the 2,3-dichloro-5,6-dicyanobenzoquinone to the pyridine is 1.5:1; a reaction temperature is the room temperature, and a reaction time is 4 to 12 hours; and in the structural formulas of the pyridine, the dihydropyridine, and the pyridine compound substituted with the trifluoromethylthio, the difluoromethylthio, or the trifluoromethyl in the meta position, R.sup.1 is hydrogen, alkyl, aryl, substituted aryl, or heteroaryl substituent; R.sup.2 is hydrogen, alkyl, halogen, amino, ether group, ester group, aryl, substituted aryl, or heteroaryl substituent; and R.sup.3 is hydrogen, alkyl, aryl, substituted aryl, or heteroaryl substituent.

2. The method according to claim 1, wherein in step S2, the trifluoromethylthio reagent is: ##STR00046## the difluoromethylthio reagent is ##STR00047## and the trifluoromethyl reagent is ##STR00048##

3. The method according to claim 2, wherein the X.sup.− is BF.sub.4.sup.−, TfO.sup.−, Cl.sup.−, Br.sup.−, or I.sup.−.

4. The method according to claim 2, wherein the R.sup.5 is aryl or substituted aryl.

5. The method according to claim 2, wherein the R.sup.6 is hydrogen or fluorine.

6. The method according to claim 1, wherein when the R.sup.1 is heteroaryl, the heteroaryl is furyl or thienyl.

7. The method according to claim 1, wherein when the R.sup.2 is heteroaryl, the heteroaryl is furyl, thienyl, or pyridyl.

8. The method according to claim 1, wherein when the R.sup.2 is halogen, the halogen is chlorine, bromine, or iodine.

9. The method according to claim 1, wherein when the R.sup.3 is heteroaryl, the heteroaryl is furyl, thienyl, or pyridyl.

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0045] The method of the present application will be illustrated in detail in conjunction with specific examples.

[0046] In the reaction formulas of the following examples, LA is a catalyst; HBpin is pinacolborane; THF is tetrahydrofuran; DCM is dichloromethane; toluene is methylbenzene; and equiv is equivalent.

Example 1

[0047] A method for preparing 3-phenyl-5-trifluoromethylthiopyridine, comprising the following steps:

[0048] S1. preparation of dihydropyridine by a hydroboration reaction, wherein in a glove box filled with nitrogen, 8 mg (0.02 mmol, 10.0 mol %) of a catalyst (LA), 1 mL of tetrahydrofuran, 28.2 mg (0.22 mmol, 1.1 equiv) of pinacolborane, and 31.0 mg (0.2 mmol, 1.0 equiv) of 3-phenylpyridine (1a) were added to an 8 mL small reaction flask, and the mixture was stirred and reacted at 80° C. for 5 hours to obtain 3-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-1,4-dihydropyridine, with the reaction formula being as follows:

##STR00011##

[0049] wherein the catalyst LA was B(2,4,6-F.sub.3C.sub.6H.sub.2).sub.3, and the structural formula thereof was as follows:

##STR00012##

[0050] S2. electrophilic substitution reaction of dihydropyridine, wherein the system was cooled to room temperature, and 62.3 mg (0.22 mmol, 1.1 equiv) of N-trifluoromethylthiosaccharin (2a) was added to the above small reaction flask and reacted at 80° C. for 2 hours to produce 3-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-5-trifluoromethylthio-1,4-dihy dropyridine, with the reaction formula being as follows:

##STR00013##

and

[0051] S3. oxidative aromatization to obtain a meta-substituted pyridine compound, wherein the system was cooled to room temperature, the small reaction flask was removed from the glove box, and the system was stirred in the air for 4 hours to produce 3-phenyl-5-trifluoromethylthiopyridine (3a), with the reaction formula being as follows:

##STR00014##

[0052] After the reaction was complete, the solvent was removed by rotary evaporation, and the residue was separated and purified by silica gel column chromatography to obtain the product 3-phenyl-5-trifluoromethylthiopyridine as a colorless oil with a yield of 94%.

[0053] The product was characterized as follows:

[0054] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.94 (s, 1H), 8.81 (s, 1H), 8.16 (s, 1H), 7.61-7.57 (m, 2H), 7.54-7.49 (m, 2H), 7.48-7.43 (m, 1H). 13C NMR (101 MHz, CDCl.sub.3) δ 154.0, 150.2, 141.8, 137.7, 136.1, 129.4, 129.2 (q, J=308.8 Hz, SCF.sub.3), 128.9, 127.3, 122.1 (q, J=1.5 Hz). .sup.19F NMR (376 MHz, CDCl.sub.3) δ −42.14 (s, SCF.sub.3). HRMS (ESI) calcd. for C.sub.12H.sub.9F.sub.3NS+(M+H).sup.+: 256.0402, Found: 256.0402.

Example 2

[0055] A method for preparing 4-phenyl-3-trifluoromethylthiopyridine, comprising the following steps:

[0056] S1. in a glove box filled with nitrogen, 8 mg (0.02 mmol, 10.0 mol %) of a catalyst (LA), 1 mL of tetrahydrofuran, 28.2 mg (0.22 mmol, 1.1 equiv) of pinacolborane, and 31.0 mg (0.2 mmol, 1.0 equiv) of 4-phenylpyridine (1b) were added to an 8 mL small reaction flask, and the mixture was stirred and reacted at 80° C. for 12 hours to obtain 4-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-1,2-dihydropyridine, with the reaction formula being as follows:

##STR00015##

[0057] wherein the catalyst LA was the same as in Example 1, i.e., B(2,4,6-F.sub.3C.sub.6H.sub.2).sub.3;

[0058] S2. the system was cooled to room temperature, and 62.3 mg (0.22 mmol, 1.1 equiv) of N-trifluoromethylthiosaccharin (2a) was added to the above small reaction flask and reacted at room temperature for 12 hours to produce 4-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-3-trifluoromethylthio-1,2-dihydropyridine, with the reaction formula being as follows:

##STR00016##

and

[0059] S3. the system was cooled to room temperature, the small reaction flask was removed from the glove box, and the system was stirred in the air for 4 hours to produce 4-phenyl-3-trifluoromethylthiopyridine (3b), with the reaction formula being as follows:

##STR00017##

[0060] After the reaction was complete, the solvent was removed by rotary evaporation, and the residue was separated and purified by silica gel column chromatography to obtain the product 4-phenyl-3-trifluoromethylthiopyridine as a white solid with a yield of 56%.

[0061] The product was characterized as follows:

[0062] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.96 (s, 1H), 8.72 (d, J=5.0 Hz, 1H), 7.50-7.43 (m, 3H), 7.38 (d, J=5.0 Hz, 1H), 7.36-7.33 (m, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 157.2, 155.5, 151.6, 137.5, 129.2, 129.1 (q, J=309.3 Hz, SCF.sub.3), 128.9, 128.4, 125.5, 120.5 (q, J=2.0 Hz). 19F NMR (376 MHz, CDCl.sub.3) δ −41.83 (s, SCF.sub.3). HRMS (ESI) calcd. for C.sub.12H.sub.9F.sub.3NS+(M+H).sup.+: 256.0402, Found: 256.0400.

Example 3

[0063] A method for preparing 2-phenyl-3,5-bis(trifluoromethylthio)pyridine, comprising the following steps:

[0064] S1. in a glove box filled with nitrogen, 13 mg (0.02 mmol, 10.0 mol %) of a catalyst (LA), 1 mL of tetrahydrofuran, 28.2 mg (0.22 mmol, 1.1 equiv) of pinacolborane, and 31.0 mg (0.2 mmol, 1.0 equiv) of 2-phenylpyridine (1c) were added to an 8 mL small reaction flask, and the mixture was stirred and reacted at 40° C. for 2 hours to obtain 2-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-1,4-dihydropyridine, with the reaction formula being as follows:

##STR00018##

[0065] wherein the catalyst LA was B(3,5-(CF.sub.3).sub.2C.sub.6H.sub.3).sub.3, and the structural formula thereof was as follows:

##STR00019##

[0066] S2. the system was cooled to room temperature, and 124.6 mg (0.44 mmol, 2.2 equiv) of N-trifluoromethylthiosaccharin (2a) was added to the above small reaction flask and reacted at 40° C. for 3 hours to produce 2-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-3,5-bis(trifluoromethylthio)-1,4-dihydropyridine, with the reaction formula being as follows:

##STR00020##

and

[0067] S3. the system was cooled to room temperature, the small reaction flask was removed from the glove box, 68.1 mg (0.3 mmol, 1.5 equiv) of 2,3-dichloro-5,6-dicyanobenzoquinone was added, and the mixture was stirred in the air for 4 hours to produce 2-phenyl-3,5-bis(trifluoromethylthio)pyridine (3c), with the reaction formula being as follows:

##STR00021##

[0068] after the reaction was complete, the solvent was removed by rotary evaporation, and the residue was separated and purified by silica gel column chromatography to obtain the product 2-phenyl-3,5-bis(trifluoromethylthio)pyridine as a colorless oil with a yield of 68%.

[0069] The product was characterized as follows:

[0070] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.94 (d, J=1.7 Hz, 1H), 8.41 (s, 1H), 7.65-7.56 (m, 2H), 7.55-7.48 (m, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 165.0, 156.3, 151.3, 137.7, 129.8, 129.7, 128.9 (q, J=309.2 Hz, SCF.sub.3), 128.9 (q, J=309.9 Hz, SCF.sub.3), 128.4, 121.9 (q, J=1.7 Hz), 121.0 (q, J=2.0 Hz). .sup.19F NMR (376 MHz, CDCl.sub.3) δ −41.45 (s, SCF.sub.3), −42.04 (s, SCF.sub.3). HRMS (ESI) calcd. for C.sub.13H.sub.8F.sub.6NS.sub.2.sup.+ (M+H).sup.+: 355.9997, Found: 355.9993.

Example 4

[0071] A method for preparing methyl 6-methyl-5-trifluoromethylthionicotinate, comprising the following steps:

[0072] S1. in a glove box filled with nitrogen, 8 mg (0.02 mmol, 10.0 mol %) of a catalyst (LA), 1 mL of tetrahydrofuran, 28.2 mg (0.22 mmol, 1.1 equiv) of pinacolborane, and 30.2 mg (0.2 mmol, 1.0 equiv) of methyl 6-methylnicotinate (1d) were added to an 8 mL small reaction flask, and the mixture was stirred and reacted at 40° C. for 4 hours to obtain methyl 6-methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-1,4-dihydropyridine-3-carboxylate, with the reaction formula being as follows:

##STR00022##

[0073] wherein the catalyst LA was the same as in Example 1, i.e., B(2,4,6-F.sub.3C.sub.6H.sub.2).sub.3;

[0074] S2. the system was cooled to room temperature, and 62.3 mg (0.22 mmol, 1.1 equiv) of N-trifluoromethylthiosaccharin (2a) was added to the above small reaction flask and reacted at room temperature for 12 hours to produce methyl 6-methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-5-trifluoromethylthio-1,4-dihydropyridine-3-carboxylate, with the reaction formula being as follows:

##STR00023##

and

[0075] S3. the system was cooled to room temperature, the small reaction flask was removed from the glove box, and the system was stirred in the air for 12 hours to produce methyl 6-methyl-5-trifluoromethylthionicotinate (3d), with the reaction formula being as follows:

##STR00024##

[0076] After the reaction was complete, the solvent was removed by rotary evaporation, and the residue was separated and purified by silica gel column chromatography to obtain the product methyl 6-methyl-5-trifluoromethylthionicotinate as a white solid with a yield of 56%.

[0077] The product was characterized as follows:

[0078] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 9.16 (d, J=1.7 Hz, 1H), 8.53 (d, J=1.7 Hz, 1H), 3.96 (s, 3H), 2.85 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 168.0, 164.7, 152.2, 146.4, 129.3 (q, J=311.1 Hz, SCF.sub.3), 125.0, 121.0 (q, J=2.0 Hz), 52.75, 24.2. .sup.19F NMR (376 MHz, CDCl.sub.3) δ −41.78 (s, SCF.sub.3). HRMS (ESI) calcd. for C.sub.9H.sub.9F.sub.3NO.sub.2S+(M+H).sup.+: 252.0301, Found: 252.0297.

Example 5

[0079] A method for preparing 5-chloro-6′-methyl-3-methylsulfonyl-5-trifluoromethylthio-2,3′-bipyridine, comprising the following steps:

[0080] S1. in a glove box filled with nitrogen, 8 mg (0.02 mmol, 10.0 mol %) of a catalyst (LA), 1 mL of tetrahydrofuran, 28.2 mg (0.22 mmol, 1.1 equiv) of pinacolborane, and 71.8 mg (0.2 mmol, 1.0 equiv) of etoricoxib (le) were added to an 8 mL small reaction flask, and the mixture was stirred and reacted at 80° C. for 8 hours to obtain 5-chloro-6′-methyl-3-(4-(methylsulfonyl)phenyl)-1′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-1′,4′-dihydro-2,3′-bipyridine, with the reaction formula being as follows:

##STR00025##

[0081] wherein the catalyst LA was the same as in Example 1, i.e., B(2,4,6-F.sub.3C.sub.6H.sub.2).sub.3;

[0082] S2. the system was cooled to room temperature, and 62.3 mg (0.22 mmol, 1.1 equiv) of N-trifluoromethylthiosaccharin (2a) was added to the above small reaction flask and reacted at 80° C. for 4 hours to obtain 5-chloro-6′-methyl-3-(4-(methylsulfonyl)phenyl)-1′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-5′-trifluoromethylthio-1′,4′-dihydro-2,3′-bipyridine, with the reaction formula being as follows:

##STR00026##

and

[0083] S3. the system was cooled to room temperature, the small reaction flask was removed from the glove box, and the system was stirred in the air for 4 hours to produce 5-chloro-6′-methyl-3-(4-(methylsulfonyl)phenyl)-5′((trifluoromethyl)thio)-2,3′-bipyridine (3e), with the reaction formula being as follows:

##STR00027##

[0084] After the reaction was complete, the solvent was removed by rotary evaporation, and the residue was separated and purified by silica gel column chromatography to obtain the product 5-chloro-6′-methyl-3-methylsulfonyl-5-trifluoromethylthio-2,3′-bipyridine as a white solid with a yield of 65%.

[0085] The product was characterized as follows:

[0086] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.73 (d, J=1.7 Hz, 1H), 8.66 (d, J=1.7 Hz, 1H), 7.93 (d, J=8.1 Hz, 2H), 7.77-7.74 (m, 2H), 7.40 (d, J=8.1 Hz, 2H), 3.06 (s, 3H), 2.75 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 163.2, 151.9, 150.5, 148.7, 146.1, 143.1, 140.6, 138.2, 135.7, 132.9, 131.8, 130.3, 129.2 (q, J=309.3 Hz, SCF.sub.3), 128.3, 112.0 (d, J=1.8 Hz), 44.41, 23.67. .sup.19F NMR (376 MHz, CDCl.sub.3) δ −41.82 (s, SCF.sub.3). HRMS (ESI) calcd. for C.sub.19H.sub.15ClF.sub.3N.sub.2O.sub.2S.sub.2.sup.+ (M+H).sup.+: 459.0210, Found: 459.0208.

Example 6

[0087] A method for preparing N,N-diethyl-5-trifluoromethylthionicotinamide, comprising the following steps:

[0088] S1. in a glove box filled with nitrogen, 8 mg (0.02 mmol, 10.0 mol %) of a catalyst (LA), 1 mL of tetrahydrofuran, 28.2 mg (0.22 mmol, 1.1 equiv) of pinacolborane, and 35.6 mg (0.2 mmol, 1.0 equiv) of nicotinoyl diethylamine (1f) were added to an 8 mL small reaction flask, and the mixture was stirred and reacted at 80° C. for 8 hours to obtain NA-diethyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-1,4-dihydropyridine-3-carboxamide, with the reaction formula being as follows:

##STR00028##

[0089] wherein the catalyst LA was the same as in Example 1, i.e., B(2,4,6-F.sub.3C.sub.6H.sub.2).sub.3;

[0090] S2. the system was cooled to room temperature, and 62.3 mg (0.22 mmol, 1.1 equiv) of N-trifluoromethylthiosaccharin (2a) was added to the above small reaction flask and reacted at 80° C. for 4 hours to produce NA-diethyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-5-trifluoromethylthio-1,4-dihydropyridine-3-carboxamide, with the reaction formula being as follows:

##STR00029##

and

[0091] S3. the system was cooled to room temperature, the small reaction flask was removed from the glove box, and the system was stirred in the air for 12 hours to produce NA-diethyl-5-trifluoromethylthionicotinamide (3f), with the reaction formula being as follows:

##STR00030##

[0092] After the reaction was complete, the solvent was removed by rotary evaporation, and the residue was separated and purified by silica gel column chromatography to obtain the product N,N-diethyl-5-trifluoromethylthionicotinamide as a colorless oil with a yield of 76%.

[0093] The product was characterized as follows:

[0094] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.85 (s, 1H), 8.74 (s, 1H), 8.01 (s, 1H), 3.56 (q, J=6.7 Hz, 2H), 3.25 (q, J=6.7 Hz, 2H), 1.27 (t, J=6.5 Hz, 3H), 1.15 (t, J=6.5 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 166.9, 156.0, 149.4, 141.6, 133.8, 129.0 (q, J=309.2 Hz, SCF.sub.3), 122.1 (q, J=2.0 Hz), 43.6, 39.9, 14.3, 12.9. .sup.19F NMR (376 MHz, CDCl.sub.3) δ −42.06 (s, SCF.sub.3). HRMS (ESI) calcd. for C.sub.11H.sub.14F.sub.3N.sub.2OS.sup.+ (M+H).sup.+: 279.0773, Found: 279.0774.

Example 7

[0095] A method for preparing 3-difluoromethylthio-5-phenylpyridine, comprising the following steps:

[0096] S1. in a glove box filled with nitrogen, 8 mg (0.02 mmol, 10.0 mol %) of a catalyst (LA), 1 mL of tetrahydrofuran, 28.2 mg (0.22 mmol, 1.1 equiv) of pinacolborane, and 31.0 mg (0.2 mmol, 1.0 equiv) of 3-phenylpyridine (1a) were added to an 8 mL small reaction flask, and the mixture was stirred and reacted at 80° C. for 5 hours to obtain 3-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-1,4-dihydropyridine, with the reaction formula being as follows:

##STR00031##

[0097] wherein the catalyst LA was the same as in Example 1, i.e., B(2,4,6-F.sub.3C.sub.6H.sub.2).sub.3;

[0098] S2. the system was cooled to room temperature, and 50.4 mg (0.22 mmol, 1.1 equiv) of 2-(difluoromethylthio)isoindole-1,3-dione (2b) was added to the above small reaction flask and reacted at 80° C. for 6 hours to produce 3-difluoromethylthio-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-5-phenyl-1,4-dihydropyridine, with the reaction formula being as follows:

##STR00032##

and

[0099] S3. the system was cooled to room temperature, the small reaction flask was removed from the glove box, and the system was stirred in the air for 4 hours to produce 3-difluoromethylthio-5-phenylpyridine (3g), with the reaction formula being as follows:

##STR00033##

[0100] After the reaction was complete, the solvent was removed by rotary evaporation, and the residue was separated and purified by silica gel column chromatography to obtain the product 3-difluoromethylthio-5-phenylpyridine as a colorless oil with a yield of 82%.

[0101] The product was characterized as follows:

[0102] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.89 (d, J=1.8 Hz, 1H), 8.75 (d, J=1.8 Hz, 1H), 8.10 (t, J=1.8 Hz, 1H), 7.61-7.57 (m, 2H), 7.54-7.48 (m, 2H), 7.47-7.42 (m, 1H), 6.89 (t, J=56.3 Hz, 1H, SCF.sub.2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 153.5, 149.3, 141.2, 137.4, 136.4, 129.3, 128.8, 127.3, 123.1 (t, J=2.7 Hz), 119.8 (t, J=278.8 Hz, SCF.sub.2H). .sup.19F NMR (376 MHz, CDCl.sub.3) δ −91.17 (d, J=56.5 Hz, SCF.sub.2H). HRMS (ESI) calcd. for C.sub.12H.sub.10F.sub.2NS.sup.+ (M+H).sup.+: 238.0497, Found: 238.0494.

Example 8

[0103] A method for preparing 3-difluoromethylthio-4-phenylpyridine, comprising the following steps:

[0104] S1. in a glove box filled with nitrogen, 8 mg (0.02 mmol, 10.0 mol %) of a catalyst (LA), 1 mL of tetrahydrofuran, 28.2 mg (0.22 mmol, 1.1 equiv) of pinacolborane, and 31.0 mg (0.2 mmol, 1.0 equiv) of 4-phenylpyridine (1a) were added to an 8 mL small reaction flask, and the mixture was stirred and reacted at 80° C. for 12 hours to obtain 4-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-1,2-dihydropyridine, with the reaction formula being as follows:

##STR00034##

[0105] wherein the catalyst LA was the same as in Example 1, i.e., B(2,4,6-F.sub.3C.sub.6H.sub.2).sub.3;

[0106] S2. the system was cooled to room temperature, and 50.4 mg (0.22 mmol, 1.1 equiv) of 2-(difluoromethylthio)isoindole-1,3-dione (2b) was added to the above small reaction flask and reacted at 80° C. for 6 hours to obtain 3-difluoromethylthio-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-4-phenyl-1,2-dihydropyridine, with the reaction formula being as follows:

##STR00035##

and

[0107] S3. the system was cooled to room temperature, the small reaction flask was removed from the glove box, and the system was stirred in the air for 4 hours to produce 3-difluoromethylthio-4-phenylpyridine (3h), with the reaction formula being as follows:

##STR00036##

[0108] After the reaction was complete, the solvent was removed by rotary evaporation, and the residue was separated and purified by silica gel column chromatography to obtain the product 3-difluoromethylthio-4-phenylpyridine as a white solid with a yield of 50%.

[0109] The product was characterized as follows:

[0110] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.88 (s, 1H), 8.66 (d, J=5.0 Hz, 1H), 7.49-7.44 (m, 3H), 7.40-7.36 (m, 2H), 7.34 (d, J=5.0 Hz, 1H), 6.64 (t, J=56.4 Hz, 1H, SCF.sub.2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 156.0, 154.4, 150.7, 137.7, 129.2, 128.9, 128.4, 125.3, 122.0 (t, J=2.6 Hz), 119.8 (t, J=277.1 Hz, SCF.sub.2H). .sup.19F NMR (376 MHz, CDCl.sub.3) δ −91.25 (d, J=56.3 Hz, SCF.sub.2H). HRMS (ESI) calcd. for C.sub.12H.sub.10F.sub.2NS.sup.+ (M+H).sup.+: 238.0497, Found: 238.0495.

Example 9

[0111] A method for preparing 3-phenyl-5-trifluoromethylpyridine, comprising the following steps:

[0112] S1. in a glove box filled with nitrogen, 8 mg (0.02 mmol, 10.0 mol %) of a catalyst (LA), 1 mL of tetrahydrofuran, 28.2 mg (0.22 mmol, 1.1 equiv) of pinacolborane, and 31.0 mg (0.2 mmol, 1.0 equiv) of 3-phenylpyridine (1a) were added to an 8 mL small reaction flask in this order, and the mixture was stirred and reacted at 80° C. for 5 hours to obtain 3-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-1,4-dihydropyridine, with the reaction formula being as follows:

##STR00037##

[0113] wherein the catalyst LA was the same as in Example 1, i.e., B(2,4,6-F.sub.3C.sub.6H.sub.2).sub.3;

[0114] S2. the system was cooled to room temperature, and 69.5 mg (0.22 mmol, 1.1 equiv) of 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (2c) was added to the above small reaction flask and reacted at room temperature for 1 hours to obtain 3-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-5-trifluoromethyl-1,4-dihydropyridine, with the reaction formula being as follows:

##STR00038##

and

[0115] S3. the system was cooled to room temperature, the small reaction flask was removed from the glove box, 68.1 mg (0.3 mmol, 1.5 equiv) of 2,3-dichloro-5,6-dicyanobenzoquinone was added, and the mixture was stirred in the air for 4 hours to produce 3-phenyl-5-(trifluoromethyl)pyridine (3i), with the reaction formula being as follows:

##STR00039##

[0116] After the reaction was complete, the solvent was removed by rotary evaporation, and the residue was separated and purified by silica gel column chromatography to obtain the product 3-phenyl-5-trifluoromethylpyridine as a white solid with a yield of 48%.

[0117] The product was characterized as follows:

[0118] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 9.02 (d, J=1.6 Hz, 1H), 8.87 (d, J=1.6 Hz, 1H), 8.09 (s, 1H), 7.66-7.56 (m, 2H), 7.55-7.45 (m, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 151.5, 145.2 (q, J=4.0 Hz), 136.8, 136.3, 131.3 (q, J=3.5 Hz), 129.4, 128.97, 127.30, 126.8 (q, J=32.7 Hz), 123.6 (q, J=272.8 Hz). .sup.19F NMR (376 MHz, CDCl.sub.3) δ −62.40 (s, CF.sub.3). HRMS (ESI) calcd. for C.sub.12H.sub.9F.sub.3N.sup.+ (M+H).sup.+: 224.0682, Found: 224.0679.

Example 10

[0119] A method for preparing 2-methyl-3-phenyl-5-trifluoromethylpyridine, comprising the following steps:

[0120] S1. in a glove box filled with nitrogen, 8 mg (0.02 mmol, 10.0 mol %) of a catalyst (LA), 1 mL of tetrahydrofuran, 28.2 mg (0.22 mmol, 1.1 equiv) of pinacolborane, and 33.8 mg (0.2 mmol, 1.0 equiv) of 2-methyl-3-phenylpyridine (1g) were added to an 8 mL small reaction flask in this order, and the mixture was stirred and reacted at 40° C. for 4 hours to obtain 2-methyl-3-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-1,4-dihydropyridine, with the reaction formula being as follows:

##STR00040##

[0121] wherein the catalyst LA was the same as in Example 1, i.e., B(2,4,6-F.sub.3C.sub.6H.sub.2).sub.3;

[0122] S2. the system was cooled to room temperature, and 69.5 mg (0.22 mmol, 1.1 equiv) of 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (2c) was added to the above small reaction flask and reacted at room temperature for 1 hours to obtain 2-methyl-3-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)-5-trifluoromethyl-1,4-dihydropyridine, with the reaction formula being as follows:

##STR00041##

and

[0123] S3. the system was cooled to room temperature, the small reaction flask was removed from the glove box, and the system was stirred in the air for 4 hours to produce 2-methyl-3-phenyl-5-(trifluoromethyl)pyridine (3j), with the reaction formula being as follows:

##STR00042##

[0124] After the reaction was complete, the solvent was removed by rotary evaporation, and the residue was separated and purified by silica gel column chromatography to obtain the product 2-methyl-3-phenyl-5-trifluoromethylpyridine as a colorless oil with a yield of 55%.

[0125] The product was characterized as follows:

[0126] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.76 (s, 1H), 7.74 (s, 1H), 7.49-7.40 (m, 3H), 7.34-7.29 (m, 2H), 2.57 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.2, 144.6 (q, J=4.1 Hz), 138.4, 137.0, 134.1 (q, J=3.4 Hz), 128.9, 128.7, 128.2, 123.8 (q, J=272.2 Hz), 124.3 (q, J=32.9 Hz), 23.6. .sup.19F NMR (376 MHz, CDCl.sub.3) δ −62.10 (s, CF.sub.3). HRMS (ESI) calcd. for C.sub.13H.sub.11F.sub.3N.sup.+ (M+H).sup.+: 238.0838, Found: 238.0839.