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[ CAS No. 2926-29-6 ] {[proInfo.proName]}

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Chemical Structure| 2926-29-6
Chemical Structure| 2926-29-6
Structure of 2926-29-6 * Storage: {[proInfo.prStorage]}
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Quality Control of [ 2926-29-6 ]

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Product Details of [ 2926-29-6 ]

CAS No. :2926-29-6 MDL No. :MFCD03092989
Formula : CF3NaO2S Boiling Point : -
Linear Structure Formula :- InChI Key :KAVUKAXLXGRUCD-UHFFFAOYSA-M
M.W :156.06 Pubchem ID :23690734
Synonyms :

Calculated chemistry of [ 2926-29-6 ]

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 5.0
Num. H-bond donors : 0.0
Molar Refractivity : 15.11
TPSA : 59.34 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.84 cm/s

Lipophilicity

Log Po/w (iLOGP) : -8.6
Log Po/w (XLOGP3) : 0.58
Log Po/w (WLOGP) : 2.51
Log Po/w (MLOGP) : -0.22
Log Po/w (SILICOS-IT) : 1.62
Consensus Log Po/w : -0.82

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.11
Solubility : 12.2 mg/ml ; 0.0782 mol/l
Class : Very soluble
Log S (Ali) : -1.4
Solubility : 6.22 mg/ml ; 0.0399 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.18
Solubility : 104.0 mg/ml ; 0.667 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.58

Safety of [ 2926-29-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P264-P280-P337+P313-P305+P351+P338-P302+P352-P332+P313-P362 UN#:N/A
Hazard Statements:H315-H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 2926-29-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 2926-29-6 ]

[ 2926-29-6 ] Synthesis Path-Downstream   1~80

  • 1
  • [ 108-75-8 ]
  • [ 2926-29-6 ]
  • [ 107264-00-6 ]
  • 2
  • [ 2926-29-6 ]
  • [ 99-76-3 ]
  • [ 115933-50-1 ]
  • 3
  • [ 2926-29-6 ]
  • [ 32854-09-4 ]
  • methyl S-trifluoromethyl-(L)-cysteinate hydrochloride [ No CAS ]
  • 4
  • [ 2926-29-6 ]
  • [ 120068-79-3 ]
  • [ 120068-37-3 ]
YieldReaction ConditionsOperation in experiment
80.20% With trichlorophosphate;dimethylamine p-toluenesulfonate; at 40℃; for 14h;Product distribution / selectivity; Comparative Example 13; [0123] Direct sulfinylation of N-phenyl pyrazole starting material (III) according to known methods was tested. As such, sulfinylation was attempted using CF3SO2Na in the presence of a halogenating agent such as POCl3, SOCl2 or PBr3. <n="35"/>(III) (II)The reaction reagents and conditions tested are provided in Table I below. <n="36"/>Table IUl <n="37"/>The results are provided in Table II below: Table II[0124] The reaction proceeded to the desired product, Fipronil, when SOCl2 or POCl3 were used as halogenating agents. However, PBr3 did not yield the desired product, or at least not in acceptable yield (about 6%~8% (II) in the reaction mixture, according to HPLC).
74.80% With thionyl chloride;dimethylamine p-toluenesulfonate; at 40℃; for 10h;Product distribution / selectivity; Comparative Example 13; [0123] Direct sulfinylation of N-phenyl pyrazole starting material (III) according to known methods was tested. As such, sulfinylation was attempted using CF3SO2Na in the presence of a halogenating agent such as POCl3, SOCl2 or PBr3. <n="35"/>(III) (II)The reaction reagents and conditions tested are provided in Table I below. <n="36"/>Table IUl <n="37"/>The results are provided in Table II below: Table II[0124] The reaction proceeded to the desired product, Fipronil, when SOCl2 or POCl3 were used as halogenating agents. However, PBr3 did not yield the desired product, or at least not in acceptable yield (about 6%~8% (II) in the reaction mixture, according to HPLC).
73% Example 1; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 13 ml. an- hydrous toluene (6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under an argon atmosphere. After cooling to 00C to 5 0C with an ice bath, thionylchloride (3.57 g, 30 mmol) was added slowly while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.03 g, 25 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 50 ml. of saturated NaHCO3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separa- tion the organic layer was washed once with saturated NaHCtheta3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (8.06 g, 70 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Comparative Examples; In order to demonstrate the advantages of the inventive process, the following examples are conducted employing the preparation procedure given above for example 1.
73 - 76% Example 1; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 13 ml. an- hydrous toluene (6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under an argon atmosphere. After cooling to 00C to 5 0C with an ice bath, thionylchloride (3.57 g, 30 mmol) was added slowly while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.03 g, 25 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 50 ml. of saturated NaHCO3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separa- tion the organic layer was washed once with saturated NaHCtheta3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (8.06 g, 70 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Example 12; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3- carbonitrile with trimethylamine tosylate, sodium trifluoromethylsulfinate and thionyl- chloride, in 6.5 molar equivalents of tolueneThe preparation procedure was conducted as described above for example 1. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (76 % yield, 96 % purity by quantitative HPLC).; Example 14; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with trimethylamine tosylate, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneThe preparation procedure was conducted as described above for example 11. The crude product was crystallized from refluxing toluene (100 g) affording the title com- pound as a white crystalline powder (73 % yield, 98 % purity by quantitative HPLC).
72 - 75% Example 1; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 13 ml. an- hydrous toluene (6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under an argon atmosphere. After cooling to 00C to 5 0C with an ice bath, thionylchloride (3.57 g, 30 mmol) was added slowly while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.03 g, 25 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 50 ml. of saturated NaHCO3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separa- tion the organic layer was washed once with saturated NaHCtheta3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (8.06 g, 70 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Example 7; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with pyridine tosylate, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneThe preparation procedure was conducted as described above for example 1. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (75 % yield, 94 % purity by quantitative HPLC).; Example 11; Sulfinylation of 5-amino-1 -[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with thionylchloride, triethylamine hydrochloride and dosage of potassium trifluoromethylsulfinateWithin a 750 mL reactor with a mechanical stirrer and a thermometer were placed vac- uum dried triethylamine hydrochloride (51.1 g, 368 mmol), 147 g anhydrous toluene(6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile), and thionylchloride (35.7 g, 294 mmol) under an argon atmosphere. After cooling to 00C to 5 0C with external cooling, vacuum dried potassium trifluoromethylsulfinate (50.4 g, 296 mmol) was added in three equal portions every 10 min while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (79.5 g, 245 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was kept at 5 0C for 60 min and then heated to 35 0C within 45 min. The temperature of 35 0C was kept for another 10 hours before quenching the reaction with 200 g of sodium hydroxide solution (10 wt.%).The resulting suspension was diluted with 176 mL of ethylacetate. After phase separation the organic layer was washed once with sodium hydroxide solution (10 wt.%). After phase separation, the organic layer was analyzed by quantitative HPLC (79 % yield). The content of compound F was below 2.9 weight percent in the crude mixture (without solvent). The product was crystallized from a mixture of ethylacetate and toluene affording the title compound as a white crystalline powder (77.1 g, 75 % yield, 98 % purity by quantitative HPLC).; Example 16; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3- carbonitrile with pyridine tosylate, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of toluene EPO <DP n="30"/>The preparation procedure was conducted as described above for example 11. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (72 % yield, 98 % purity by quantitative HPLC).
71% Example 1; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 13 ml. an- hydrous toluene (6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under an argon atmosphere. After cooling to 00C to 5 0C with an ice bath, thionylchloride (3.57 g, 30 mmol) was added slowly while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.03 g, 25 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 50 ml. of saturated NaHCO3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separa- tion the organic layer was washed once with saturated NaHCtheta3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (8.06 g, 70 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Example 8; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with trimethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneThe preparation procedure was conducted as described above for example 1. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (71 % yield, 97 % purity by quantitative HPLC).
67% With potassium fluoride; thionyl chloride;triethylamine hydrochloride; In toluene; at 0 - 50℃; for 5.08333h;Product distribution / selectivity; Example 5; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride under addition of potassium fluorideAn oven dried 100 mL 3 neck round bottom flask equipped with a magnetic stir bar, thermocouple, condenser, ISb inlet, and rubber septum, was charged with vacuum dried potassium fluoride (1.53 g, 26.1 mmol), anhydrous toluene (20.1 g), vacuum dried sodium trifluoromethylsulfinate (4.53 g, 29.0 mmol), and thionylchloride (3.76 g, 31.6 mmol) under nitrogen. The solution was cooled to 00C and triethylamine hydrochloride (5.44g, 39.5 mmol) was added slowly, controlling the temperature to less than 10 0C. Vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.48 g, 26.1 mmol, 99 % pure) was added at 00C. The solution was then quickly warmed to 50 0C, in less then 5 minutes, using a hot water bath. The reaction was allowed to stir for 5 hrs at 50 0C before quenching with 50 ml of saturated aqueous NaHCtheta3. The resulting suspension was diluted with 30 mL of ethylacetate and then allowed to phase separate. The aqueous phase was extracted with 30 mL ethyl acetate and the combined organic phases were washed with 30 ml of saturated aqueous NaCU3. The organic phase was concentrated under reduced pressure until dryness, affording the crude title compound (11.6 g, 67 % yield, 68.5 % purity). 1H-NMR (Bruker DRX-500, d6-DMSO): delta [ppm]: 8.33 (s), 7.57 (s).
67% Example 1; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 13 ml. an- hydrous toluene (6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under an argon atmosphere. After cooling to 00C to 5 0C with an ice bath, thionylchloride (3.57 g, 30 mmol) was added slowly while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.03 g, 25 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 50 ml. of saturated NaHCO3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separa- tion the organic layer was washed once with saturated NaHCtheta3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (8.06 g, 70 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Example 9; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with pyridine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneThe preparation procedure was conducted as described above for example 1. The crude product was crystallized from refluxing toluene (100 g) affording the title com- pound as a white crystalline powder (67 % yield, 95 % purity by quantitative HPLC).; Example 13; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3- carbonitrile with pyridine hydrochloride, sodium trifluoromethylsulfinate and thionylchlo- ride, in 6.5 molar equivalents of tolueneThe preparation procedure was conducted as described above for example 1. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (67 % yield, 95 % purity by quantitative HPLC).
65% Example 1; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 13 ml. an- hydrous toluene (6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under an argon atmosphere. After cooling to 00C to 5 0C with an ice bath, thionylchloride (3.57 g, 30 mmol) was added slowly while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.03 g, 25 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 50 ml. of saturated NaHCO3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separa- tion the organic layer was washed once with saturated NaHCtheta3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (8.06 g, 70 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Comparative Examples; In order to demonstrate the advantages of the inventive process, the following examples are conducted employing the preparation procedure given above for example 1.
63 - 75% Example 1; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 13 ml. an- hydrous toluene (6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under an argon atmosphere. After cooling to 00C to 5 0C with an ice bath, thionylchloride (3.57 g, 30 mmol) was added slowly while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.03 g, 25 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 50 ml. of saturated NaHCO3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separa- tion the organic layer was washed once with saturated NaHCtheta3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (8.06 g, 70 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Example 3; Sulfinylation of 5-amino-1 -[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile via addition of a mixture of sodium trifluoromethylsulfinate, triethylamine hydrochloride and thionylchloride to 5-amino-1-[2,6-dichloro-4- (trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrileWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 10 g anhydrous toluene under an argon atmosphere. After cooling to 0 - 5 0C with an ice bath thionylchloride (3.57 g, 30 mmol) was added while keeping the reaction temperature below 5 0C. After stirring for another 30 min the cooled sulfinic acid solution was added at once to a stirred suspension of vacuum dried 5-amino-1-(2,6-dichloro-4- trifluoromethyl-phenyl)-1 H-pyrazole-3-carbonitrile (8.03 g, 25 mmol, 99 % purity) in 5 g toluene with a temperature of 50 0C. The temperature of 50 0C was kept for another 5 hours before quenching the reaction with 50 ml. of saturated NaHCU3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separation the organic layer was washed once with saturated NaHCU3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (7.25 g, 63 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Example 11; Sulfinylation of 5-amino-1 -[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with thionylchloride, triethylamine hydrochloride and dosage of potassium trifluoromethylsulfinateWithin a 750 mL reactor with a mechanical stirrer and a thermometer were placed vac- uum dried triethylamine hydrochloride (51.1 g, 368 mmol), 147 g anhydrous toluene(6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile), and thionylchloride (35.7 g, 294 mmol) under an argon atmosphere. After cooling to 00C to 5 0C with external cooling, vacuum dried potassium trifluoromethylsulfinate (50.4 g, 296 mmol) was added in three equal portions every 10 min while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (79.5 g, 245 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was kept at 5 0C for 60 min and then heated to 35 0C within 45 min. The temperature of 35 0C was kept for another 10 hours before quenching the reaction with 200 g of sodium hydroxide solution (10 wt.%).The resulting suspension was diluted with 176 mL of ethylacetate. After phase separation the organic layer was washed once with sodium hydroxide solution (10 wt.%). After phase separation, the organic layer was analyzed by quantitative HPLC (79 % yield). The content of compound F was below 2.9 weight percent in the crude mixture (without solvent). The product was crystallized from a mixture of ethylacetate and toluene affording the title compound as a white crystalline powder (77.1 g, 75 % yield, 98 % purity by quantitative HPLC).; Example 15; Sulfinylation of 5-amino-1-[2,6...
57% Example 1; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 13 ml. an- hydrous toluene (6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under an argon atmosphere. After cooling to 00C to 5 0C with an ice bath, thionylchloride (3.57 g, 30 mmol) was added slowly while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.03 g, 25 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 50 ml. of saturated NaHCO3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separa- tion the organic layer was washed once with saturated NaHCtheta3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (8.06 g, 70 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Comparative Examples; In order to demonstrate the advantages of the inventive process, the following examples are conducted employing the preparation procedure given above for example 1.
55% Example 1; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 13 ml. an- hydrous toluene (6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under an argon atmosphere. After cooling to 00C to 5 0C with an ice bath, thionylchloride (3.57 g, 30 mmol) was added slowly while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.03 g, 25 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 50 ml. of saturated NaHCO3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separa- tion the organic layer was washed once with saturated NaHCtheta3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (8.06 g, 70 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Comparative Examples; In order to demonstrate the advantages of the inventive process, the following examples are conducted employing the preparation procedure given above for example 1.
44% Example 1; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and thionylchloride, in 6.5 molar equivalents of tolueneWithin a 3-neck, 50 ml. round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed vacuum dried sodium trifluoromethylsulfinate (4.29 g, 27.5 mmol), vacuum dried triethylamine hydrochloride (5.16 g, 37.5 mmol), and 13 ml. an- hydrous toluene (6.5 molar equivalents relative to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under an argon atmosphere. After cooling to 00C to 5 0C with an ice bath, thionylchloride (3.57 g, 30 mmol) was added slowly while keeping the reaction temperature below 5 0C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-1 H-pyrazole-3- carbonitrile (8.03 g, 25 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 50 ml. of saturated NaHCO3 solution. The resulting suspension was diluted with 30 ml. of ethylacetate. After phase separa- tion the organic layer was washed once with saturated NaHCtheta3 solution and concentrated under reduced pressure until dryness. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (8.06 g, 70 % yield, 94 % purity by quantitative HPLC). 1H-NMR (Bruker DRX-500, d6- DMSO): delta [ppm]: 8.33 (s), 7.57 (s).; Example 17; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H-pyrazole-3- carbonitrile with triethylamine tosylate, sodium trifluoromethylsulfinate and thionylchlo- ride, in 6.5 molar equivalents of tolueneThe preparation procedure was conducted as described above for example 1. The crude product was crystallized from refluxing toluene (100 g) affording the title compound as a white crystalline powder (44 % yield, 76 % purity by quantitative HPLC). No formation of insoluble material (as with diethylamine tosylate as the amine acid complex, compare example C4 of Table 3) was observed.
6 - ~ 8% With phosphorus tribromide;dimethylamine p-toluenesulfonate; at -15 - 57℃; for 2 - 14h;Product distribution / selectivity; Comparative Example 13; [0123] Direct sulfinylation of N-phenyl pyrazole starting material (III) according to known methods was tested. As such, sulfinylation was attempted using CF3SO2Na in the presence of a halogenating agent such as POCl3, SOCl2 or PBr3. <n="35"/>(III) (II)The reaction reagents and conditions tested are provided in Table I below. <n="36"/>Table IUl <n="37"/>The results are provided in Table II below: Table II[0124] The reaction proceeded to the desired product, Fipronil, when SOCl2 or POCl3 were used as halogenating agents. However, PBr3 did not yield the desired product, or at least not in acceptable yield (about 6%~8% (II) in the reaction mixture, according to HPLC).
57.3%Chromat. Example 6; Sulfinylation of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1 H- pyrazole-3-carbonitrile with triethylamine hydrochloride, sodium trifluoromethylsulfinate and phosporoxychlorideWithin a 3-neck, 50 mL round bottom flask equipped with a magnetic stirrer bar and a thermometer were placed sodium trifluoromethylsulfinate (8.84 g, 55.0 mmol) and 40 mL dried toluene (6.8 molar equivalents relative to 5-amino-1-[2,6-dichloro-4- (trifluoromethyl)phenyl]-1 H-pyrazole-3-carbonitrile) under a nitrogen atmosphere. After cooling to 00C to 5 0C with an ice bath, phosphoroxychloride (9.20 g, 60.0 mmol) was added slowly while keeping the reaction temperature below 5 0C. After complete addi- tion of phosphoroxychloride, triethylamine hydrochloride (10.32g, 75.0 mmol) was added at 5C. After stirring for another 30 min, vacuum dried 5-amino-1-(2,6-dichloro-4- EPO <DP n="27"/>trifluoromethyl-phenyl)-1 H-pyrazole-3-carbonitnle (16.06 g, 50 mmol, 99 % purity) was added at 5 0C, and the reaction mixture was heated to 50 0C within 5 min by a preheated water bath. The temperature of 50 0C was kept for another 6 hours before quenching the reaction with 100 g of 10% NaHCO3 solution. The resulting suspension was diluted with 100 ml. of ethylacetate. After phase separation, the organic layer was analyzed by quantitative HPLC (57.3% yield).

  • 5
  • [ 2926-29-6 ]
  • [ 120068-79-3 ]
  • [ 120067-83-6 ]
YieldReaction ConditionsOperation in experiment
>= 96% In a three-necked flask equipped with a dropping funnel, a stirrer and a thermometer was added lmol of 5-amino-3-cyano-1-(2,6-dichloro-4- (trifluoromethyl) phenyl) -pyrazole (II), 1.5piomicron1 sodium trifluoromethylsulfinate, 800ml of toluene and 0.08 mol (III) ionic liquid,After stirring for 5 min, the mixture was cooled to -2 C with stirring under ice-cooling. The mixture was stirred under stirringIn the above reactor, a solution of 1.2 mol of phosphorus trichloride in 80 ml of toluene was slowly added dropwise, stirred and heated to 50 C for 5 h,The reaction was quenched with ice water, extracted with methylene chloride, the organic phase was kept and washed once with saturated sodium bicarbonate, washed with brine. 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-(trifluoromethylthio)-1H-pyrazole-3-carbonitrile(0.965mol, ? 96% yield) (I),, the purity was 97.7%; further recrystallization was carried out using toluene, and the yield was 90%To give a purity of ? 99% (yield ? 94%)
66.7% Example 7 - Laboratory scale preparation of compound of formula I[0101] In a 3 L four-necked flask equipped with a thermometer, a drop funnel and a mechanical stirrer, 200 g of 5-amino-l-(2,6-dichloro-4- (trifluoromethyl)phenyl)-lH-pyrazole-3-carbonitrile (compound of formula III), 194.4 g of CF3SO2Na obtained in Example 5, 206.2 g of catalyst PTSA.NetaMe2 obtained in Example 6, and 1750 mL of toluene were added. The resulting mixture was stirred at room temperature (25 +/- 5C) for 15 minutes, and 2.00 mL of DMF was added. The resulting mixture was stirred at room temperature for 30 minutes. The mixture was cooled to 0 +/- 2C, and PCl3 (85.0 g) was added dropwise at that temperature. The resulting mixture was stirred at 0 +/- 2C for 1 hour. It was then warmed to room temperature and stirred for 1 hour at 20 +/- 5C. The mixture was <n="30"/>then heated to 70C+/- 5C, and was stirred at that temperature for 6 hours. [0102] Water (800 mL) and 300 mL of ethyl acetate were added. The resulting mixture was stirred for 30 minutes, cooled at room temperature and separated. The organic layer was concentrated under vacuum at 50C to give 350.7 g of residue. Toluene (600 mL) was added to the residue. The resulting mixture was heated to 90 +/- 5C, then slowly cooled to ~10-15C, and stirred for 2 hours at that temperature. The mixture was filtered, and the filter cake was dried under vacuum at 60 +/- 2C to give 181.7 g of desired product (66.7% yield; 97.7% pure). [0103] The reaction was also conducted in a variety of other solvents in good yields. For example, the thioether (I) can be prepared from 5-amino-l-(2,6- dichloro-4-(trifluoromethyl)phenyl)- lH-pyrazole-3-carbonitrile (compound of formula III) using the experimental protocol described above, wherein DMF is replaced with n-heptane, cyclohexane, benzene, xylene, tert-butyl methyl ether (TBME), TetaF, chloroform, ethyl acetate, dichloromethane, 1,2-dichloroethane, 2- methyltetrahydrofuran, acetonitrile or CCl4.
Example 3 - Industrial scale preparation of compound of formula I [0092] In a 200 L reactor, 12.0 kg of 5-amino-l-(2,6-dichloro-4- (trifluoromethyl)phenyl)-lH-pyrazole-3-carbonitrile (compound of formula III), 11.7 kg of CF3SO2Na obtained in Example 1, 12.4 kg of catalyst PTSA.NetaMe2 obtained in Example 2, and 90.8 kg of toluene were added. The resulting mixture was stirred at room temperature (25 +/- 5C) for 15 minutes, and 0.11 kg of DMF was added. The resulting mixture was stirred at room temperature for 30 minutes. The mixture was cooled to 0 +/- 20C, and PCl3 (5.1 g) was added dropwise at that temperature. The resulting mixture was stirred at 0 +/- 2C for 1 hour. It was then warmed to room temperature and stirred for 1 hour at 20 +/- 50C. The mixture was then heated to ~65-70C, and was stirred at that temperature for 8 hours. [0093] Water (48.0 kg) and 16.1 kg of ethyl acetate were added. The resulting mixture was stirred for 30 minutes, cooled at room temperature and separated. The organic layer was concentrated under vacuum at 65C. Toluene (31.1 kg) was added to the residue. The resulting mixture was heated to 90 +/- 50C, then slowly cooled to -10- 150C, and stirred for 2 hours at that temperature. The mixture was filtered, and the filter cake was dried under vacuum at 60 +/- 2C. If the purity of the crude product was < 96%, it was recrystallized from toluene.
  • 6
  • [ 40299-87-4 ]
  • [ 2926-29-6 ]
  • [ 1315549-93-9 ]
YieldReaction ConditionsOperation in experiment
52% In N,N-dimethyl acetamide; at 70℃; for 72h;Inert atmosphere; 2-bromo-1-morpholinoethanone (202 mg, 0.97 mmol, 1.0 equiv.) and sodium trifluoromethanesulfinate (311 mg, 1.94 mmol, 2.0 equiv.) were dissolved in DMA (2 mL), and the mixture was stirred for 3 days at 70 C under N2. The reaction was cooled to 60 C, concentrated to dryness, diluted with ether, filtered over Celite, and concentrated to dryness again. The resulting residue was purified by automated flash chromatography (10 g silica column, 50% EtOAc/hex) to afford 2-(trifluoromethanesulfonyl)-1-morpholinoethanone 11 (133 mg, 0.51 mmol, 52%) as a white solid.
  • 7
  • [ 5720-05-8 ]
  • [ 2926-29-6 ]
  • [ 6140-17-6 ]
  • 8
  • [ 16419-60-6 ]
  • [ 2926-29-6 ]
  • [ 13630-19-8 ]
  • 9
  • [ 101251-09-6 ]
  • [ 2926-29-6 ]
  • [ 349-97-3 ]
  • 10
  • [ 15715-58-9 ]
  • [ 2926-29-6 ]
  • [ 6858-46-4 ]
  • C16H23F3N2O17P2*2.3C6H15N [ No CAS ]
  • 11
  • [ 2050-46-6 ]
  • [ 2926-29-6 ]
  • [ 639462-74-1 ]
  • 12
  • [ 6099-03-2 ]
  • [ 2926-29-6 ]
  • [ 1373497-84-7 ]
  • 13
  • [ 2316-26-9 ]
  • [ 2926-29-6 ]
  • [ 1418317-22-2 ]
  • [ 1418317-38-0 ]
  • 14
  • [ 850623-36-8 ]
  • [ 2926-29-6 ]
  • [ 455-18-5 ]
  • 15
  • [ 2926-29-6 ]
  • [ 374564-35-9 ]
  • [ 402-43-7 ]
  • 16
  • [ 2926-29-6 ]
  • potassium o-tolyltrifluoroborate [ No CAS ]
  • [ 13630-19-8 ]
  • 17
  • [ 2926-29-6 ]
  • [ 253342-48-2 ]
  • [ 401-79-6 ]
  • 18
  • [ 2926-29-6 ]
  • potassium (4-methylphenyl)trifluoroborate [ No CAS ]
  • [ 6140-17-6 ]
  • 19
  • [ 73-31-4 ]
  • [ 2926-29-6 ]
  • [ 205675-33-8 ]
  • 20
  • [ 2926-29-6 ]
  • [ 92-48-8 ]
  • [ 1562426-71-4 ]
YieldReaction ConditionsOperation in experiment
57% With dipotassium hydrogenphosphate; In acetone; at 20℃; for 12h;Inert atmosphere; Irradiation; Green chemistry; General procedure: To a tube were added 1a (1.0 equiv), CF 3 SO 2 Na(4.0 equiv),K 2 HPO 4 , Acetone (2 mL). Then the tube was evacuated and backlledwith argon for three times. The tube around condensate water wasstirred at room temperature in argon with the irradiation of Xenon lampfor 12 h. After the reaction was nished, the mixture was washed withsaturated sodium chloride solution and then extracted with ethylacetate for three times. The combined organic layers were dried overNa 2 SO 4 and concentrated under reduced pressure, then puried bychromatography on silica gel.
  • 21
  • [ 1810-66-8 ]
  • [ 2926-29-6 ]
  • [ 1579270-42-0 ]
  • 23
  • [ 2926-29-6 ]
  • [ 66-22-8 ]
  • [ 54-20-6 ]
YieldReaction ConditionsOperation in experiment
91.9% With sodium persulfate; copper(II) sulfate; In water; at 60 - 65℃; for 6h; With a thermometer,11.2 g of uracil (0.1 mol) was added to the reaction vessel of the stirrer.23.4 g of sodium trifluoromethylsulfinate (0.15 mol), dissolved in 150 ml of water,Raise the temperature to 60 C, control the reaction temperature at 60 ~ 65 C,Add 50 grams of sodium persulfate and 5 grams in batchesThrough a mixture of copper sulfate,After reacting for 6 hours, after evaporating 100 ml of water,It was cooled and precipitated, and dried by filtration to obtain 14.7 g of 5-trifluoromethyluracil (I). HPLC was more than 99%.The yield was 91.9%.
71.1% With di-tert-butyl peroxide; sodium sulfite; In dichloromethane; water; at 0 - 10℃; for 8h; The mixture was treated with dichloromethane and water as the reaction solvent and tert-butyl peroxide as catalyst. The synthesis route was as follows:The specific steps are:[0016] (1) Under stirring conditions,To a 10 L three-necked flask was added 112 g of ureidine,Lkg of sodium trifluoromethanesulfinate, 2 L of deionized water at a temperature of 0 C and 4 L of dichloromethane, and the mixture was homogeneously added to a three-necked flask.9L mass fraction70% of the aqueous solution of t-butyl peroxide, the temperature of the process does not exceed 10 C,Dropwise for 2 hours; during the dropwise addition, 12.6 g of sodium sulfite was added in 3 batches, plus 4.2 g per batch;(2) The reaction was stopped after 8 hours of continued reaction; the temperature of the reaction system was slowly increased during the reaction. After the solution in the three-necked flask was cooled to room temperature (25 C), add sodium carbonate to the solution to the solution. The solution was filtered and the filtrate was extracted with 10 L of ethyl acetate three times. The organic layer was washed with deionized water, dried over anhydrous sodium sulfate and concentrated to give a white solid 5-trifluoromethyluracil. The mass of the product was 128 g, and the yield was 71.1%, which was significantly higher than that of the prior art. By mass spectrometry, the results are as follows:
Pretreatment of Commercial Grade Sodium Trifluoromethanesulfinate (CF3SO2Na)10055] A 1 L jacket reactor (reactor A) is charged with CF3SO2Na (125.0 g, 65% purity, 0.52 mol, 2.89 eq.) followed by ethyl acetate (625.0 g). The resulting suspension is heated to 40-50 C. and kept stirring at this temperature for 1 h. The suspension is filtered with the aid of Celite (5.0 g) at 30-50 C. and the cake is washed with ethyl acetate (50 g). The combined filtrate is transferred to a 500 mLjacket reactor (reactor B) and concentrated to about 80-100 mE (jacket temperature 70 C./100-500 mbar). Water (100 mE) is added into the mixture. The resulting biphasic mixture is concentrated to about 90 mE (jacket temperature 70 C./100-500 mbar) to remove residual ethyl acetate.TrifluoromethylationUracil (20.0 g, 0.18 mol, 1.0 eq.), silica gel (4.0 g), ferrous sulfate (Fe504) heptahydrate (2.0 g, 0.007 mol, 0.04 eq.) and water (100.0 mE) are charged into reactor B. The resulting suspension is heated to 45-50 C., tert-butyl hydroperoxide (91.8 g, 0.71 mol, 70% aqueous solution, 3.9 eq.) is added slowly into the mixture through an addition funnel while keeping the internal temperature between 45-55 C. during addition by controlling the addition rate and jacket reactor in about 30 mm. A strong exotherm together with release of gas is observed during the addition of the tert-butyl hydroperoxide. A large amount of SO3 and trace amount of HF are detected. Silica gel is used to minimize the corrosion of the glass reactot After the addition, the internal temperature is kept to 60-70 C. for 1.0-1.5 h. The reaction is monitored by HPEC until ratio ofuracil:5-TFU 97% (220 nm). (Note: The resulting product containing some inorganic impurities was used directly in the following chlorination step. Around 4 g of product is lost in the aqueous mother liquor, which can be recovered by extraction with THF if necessary.) (Note: From a quality point of view the reaction without FeSO4 and silica gel gives similar results)5-trifluoromethyluracil (5-TFU)White solid.?H NMR (CD3COCD3): oe 8.1 (s, 1H), 10.5 (brs,10058] ?9F NMR (CD3COCD3): oe -63.810059] ESI MS (mlz) 179 [M-1]10056]10057]2H).
73%Chromat. With tert.-butylhydroperoxide; ferrous(II) sulfate heptahydrate; In water; at 45 - 70℃; Pretreatment of commercial grade sodium trifluoromethanesulfinate (CF3S02Na) A 1 L jacket reactor (reactor A) is charged with CF3S02Na (125.0 g, ~ 65 % purity, ~ 0.52 mol, 2.89 eq.) followed by ethyl acetate (625.0 g). The resulting suspension is heated to 40-50 C and kept stirring at this temperature for 1 h. The suspension is filtered with the aid of Celite (5.0 g) at 30-50 C and the cake is washed with ethyl acetate (50 g). The combined filtrate is transferred to a 500 mL jacket reactor (reactor B) and concentrated to about 80-100 mL (jacket temperature 70 C/100-500 mbar). Water (100 mL) is added into the mixture. The resulting biphasic mixture is concentrated to about 90 mL (jacket temperature 70 C/100-500 mbar) to remove residual ethyl acetate. Trifluoromethylation Uracil (20.0 g, 0.18 mol, 1 .0 eq.), silica gel (4.0 g), ferrous sulfate (FeS04) heptahydrate (2.0 g, 0.007 mol, 0.04 eq.) and water (100.0 mL) are charged into reactor B. The resulting suspension is heated to 45-50 C, ie f-butyl hydroperoxide (91 .8 g, 0.71 mol, 70 % aqueous solution, 3.9 eq.) is added slowly into the mixture through an addition funnel while keeping the internal temperature between 45-55 C during addition by controlling the addition rate and jacket reactor in about 30 min. A strong exotherm together with release of gas is observed during the addition of the ie f-butyl hydroperoxide. A large amount of S03 and trace amount of HF are detected. Silica gel is used to minimize the corrosion of the glass reactor. After the addition, the internal temperature is kept to 60-70 C for 1.0-1.5 h. The reaction is monitored by HPLC until ratio of uracil:5-TFU < 3:97 (HPLC area). Aqueous sodium sulfite solution (15 g (15 weight %), 0.0178 mol, 0.1 eq.) is added and stirred for another 30 min between 60-70 C to quench residual ie f-butyl hydroperoxide. The peroxide level is checked with test strip (Merckoquant 1 1001 1 test strips until it is lower than 10 ppm). The mixture is then cooled to 25-35 C, diluted with THF (40 ml_), the resulting mixture is filtered (to remove silica gel) and the filter cake is washed with THF (20 ml_). The combined filtrate is concentrated to about 170-190 mL (jacket temperature 70 C/100-500 mbar). The resulting suspension is cooled to 10-15 C in 2 h and held at this temperature for 1 h. The suspension is filtered, the filter cake is washed with cold water (20 mL) and dried at 45-50 C to obtain white crystal (24 g; crude yield 75 %, HPLC assay yield is 73 %, area purity > 97% (220 nm). (Note: The resulting product containing some inorganic impurities was used directly in the following chlorination step. Around 4 g of product is lost in the aqueous mother liquor, which can be recovered by extraction with THF if necessary.) (Note: From a quality point of view the reaction without FeS04 and silica gel gives similar results) 5-trifluoromethyluracil (5-TFU) White solid. 1H NMR (CD3COCD3): delta 8.1 (s, 1 H), 10.5 (brs, 2H). 19F NMR (CD3COCD3): delta -63.8 ESI MS (m/z) 179 [M-1 ]"

  • 24
  • [ 2926-29-6 ]
  • [ 106-40-1 ]
  • [ 445-02-3 ]
  • 25
  • [ 455-14-1 ]
  • [ 2926-29-6 ]
  • [ 367-71-5 ]
  • 26
  • [ 2926-29-6 ]
  • [ 100-01-6 ]
  • [ 121-01-7 ]
  • 27
  • [ 2926-29-6 ]
  • [ 153286-94-3 ]
  • 3,3,3-trifluoro-1-(pyrimidin-5-yl)propan-1-one [ No CAS ]
  • 28
  • [ 13737-36-5 ]
  • [ 2926-29-6 ]
  • C10H9F3O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With potassium iodide; In N,N-dimethyl-formamide; at 120℃; for 0.25h; Example 1 Synthesis of Compound I-35 Step 1 A solution of compound 4 (525 mg, 2.29 mmol), sodium trifluoromethanesulfinate (1.07 g, 6.88 mmol) and potassium iodide (76.0 mg, 0.458 mmol) in DMF (5 mL) was stirred at 120 C. for 15 minutes. To the reaction mixture was added water -2 mol/L hydrochloric acid and the precipitate was filtered. The resulting solid was washed by water and dried over to afford compound 5 (580 mg, yield: 90%). 1H-NMR (CDCl3) delta: 3.70 (2H, s), 4.46 (2H, s), 7.34-7.43 (4H, m).
  • 29
  • [ 2926-29-6 ]
  • [ 4044-98-8 ]
  • 6-bromo-2-phenyl-3-(trifluoromethyl)imidazo[1,2-a]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With 3,6?di?tert?butyl?9?mesityl?10?phenylacridin?10?ium tetrafluoroborate; In 1,2-dichloro-ethane; at 20℃; for 24h;Inert atmosphere; Irradiation; Add 2-phenyl-6-bromoimidazo [1,2-a] pyridine 0.3mmol,sodium trifluoromethanesulfinate 0.2mmol,0.01 mmol of 3,6-di-tert-butyl-9- mesityl-10-phenylacridine-10-tetrafluoroborate photocatalyst was added to the reaction tube,Add 2.0 mL of 1,2-dichloroethane solvent and react at room temperature for 24 hours under the irradiation of a blue LED lamp;After the reaction, the reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure, and purified by column chromatography to obtain the target product in a yield of 62%.
  • 30
  • [ 19063-55-9 ]
  • [ 2926-29-6 ]
  • 6-bromo-3-(trifluoromethyl)-2H-1-benzopyran-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With dipotassium hydrogenphosphate; In acetone; at 20℃; for 12h;Inert atmosphere; Irradiation; Green chemistry; General procedure: To a tube were added 1a (1.0 equiv), CF 3 SO 2 Na(4.0 equiv),K 2 HPO 4 , Acetone (2 mL). Then the tube was evacuated and backlledwith argon for three times. The tube around condensate water wasstirred at room temperature in argon with the irradiation of Xenon lampfor 12 h. After the reaction was nished, the mixture was washed withsaturated sodium chloride solution and then extracted with ethylacetate for three times. The combined organic layers were dried overNa 2 SO 4 and concentrated under reduced pressure, then puried bychromatography on silica gel.
  • 31
  • [ 2926-29-6 ]
  • [ 1193-02-8 ]
  • [ 372-16-7 ]
  • 32
  • [ 5585-96-6 ]
  • [ 2926-29-6 ]
  • 3-((trifluoromethyl)thio)-1H-indol-4-yl acetate [ No CAS ]
  • 33
  • [ 2926-29-6 ]
  • [ 33332-29-5 ]
  • 5-chloro-3-(trifluoromethyl)pyrazin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With tert.-butylhydroperoxide; In dichloromethane; for 8h; Step A: To a solution of sodium trifluoromethanesulfinate (1.2 g, 7.7 mmol) in water (12 ml) was added a solution of <strong>[33332-29-5]5-chloropyrazin-2-amine</strong> (1.0 g, 7.7 mmol) in DCM (30 ml), tert- Butylhydroperoxide (1.0 ml, 5.5 M in nonane, 5.5 mmol) was added dropwise over 2 h. A second portion of sodium trifluoromethanesulfinate (1.2 g, 7.7 mmol) was then added followed by a second portion of tert-butylhydroperoxide (1.0 ml, 5.5 M in nonane, 5.5 mmol) was added dropwise over 6 h. The reaction was repeatedly extracted with DCM and the combined organic extracts washed with brine, dried (Na2S04) and concentrated. Purification by flash column chromatography on silica gel (DCM) afforded 5-chloro-3-(trifluoromethyl)pyrazin-2-amine as yellow crystals (0.9 g, 57%). MS (m/e): 198.0. (M+H+, CI)
  • 34
  • [ 2926-29-6 ]
  • [ 52421-75-7 ]
  • 6-ethyl-2-methyl-5-(trifluoromethyl)pyrimidin-4(3H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With tert-Butyl peroxybenzoate; In water; at 80.0℃; for 2.0h; 1 mmol of pyrimidinone compound, 1 mmol of sodium trifluoromethylsulfinate, 2 mmol of tert-butyl perbenzoate, and 1 mL of water were added to the reaction tube, and the reaction was carried out at 80 C for 2 hours, and the reaction was completed by column chromatography to obtain the following target. After identification, the spectral data corresponded to the structural formula, and it was confirmed that the synthesis was 6-ethyl-2-methyl-5-(trifluoromethyl)pyrimidin-4(3H)-one in a yield of 97%.
73% With manganese(III) triacetate dihydrate; In acetic acid; at 25.0℃; for 12.0h; General procedure: To a solution of 2,6-diphenylpyrimidinone (1a) (0.16 g, 0.5 mmol) and sodium trifluoromethanesulfinate 2 (0.258 g, 1.5 mmol) in acetic acid (10 mL), was added manganese triacetate hydrate (0.402 g, 1.5 mmol) in batches. The mixture was stirred at 25 C in air for 12 h. After the completion of the reaction, water (20 mL) was added to the reaction mixture, extracted with ethyl acetate (15 mL*3). The combined organic fractions were dried over anhydrous Na2SO4, and concentrated under vacuum to give the crude product, which was purified by flash column chromatography (silica gel, petroleum ether/ethyl acetate=2:1) to give 2,6-diphenyl-5-trifluoromethylpyrimidinone (3a). 6-Ethyl-2-methyl-5-(trifluoromethyl)pyrimidin-4(3H)-one (3k). White solid, 73% yield (75 mg), mp 163-165 C. 1H NMR (DMSO-d6, 400 MHz): delta 12.95 (s, 1H), 2.67-2.57 (m, 2H), 2.32 (s, 3H), 1.15 (t, J=7.5 Hz, 3H). 13C NMR (DMSO-d6, 101 MHz): delta 167.4, 162.1, 159.7, 124.6 (q, J=273.1 Hz), 110.0 (q, J=29.1 Hz), 29.4, 21.7, 13.5. 19F NMR (DMSO-d6, 376 MHz): delta -56.1 (CF3). HRMS (CI-TOF) m/z: (M+H)+ Anal. Calcd for C8H9F3N2O 207.0745, found 207.0743.
  • 35
  • [ 693-98-1 ]
  • [ 2926-29-6 ]
  • [ 33468-67-6 ]
  • 36
  • [ 951-78-0 ]
  • [ 2926-29-6 ]
  • [ 70-00-8 ]
YieldReaction ConditionsOperation in experiment
94.3% With tert.-butylhydroperoxide; In water; at -3 - 60℃; for 2.0h;Inert atmosphere; 456 g (2 mol) of 2'-deoxyuridine and 985.2 g (6 mol)95% sodium trifluoromethanesulfinate was added to 7.98 L of purified water, stirred down to -3 C, protected by nitrogen stream,After stirring, 772 g (6 mol) of 70% t-butyl hydroperoxide was added dropwise, and the temperature was less than 5 C during the dropwise addition,After the dropwise addition, the temperature was raised to 60 C, the reaction was stirred for 2 hours, and the reaction was completed.Drop to room temperature, respectively, 8L ethyl acetate extraction 3 times, the combined extract,50 deg.] C and concentrated under reduced pressure to give 558g trifluridine, yield: 94.3%, purity: 97.2%.
59% With tert-butyl alcohol; In water; at 0 - 20℃; for 3.0h; To a solution of 2'-deoxyuridine (1, 381 mg, 1.67 mmol) and CF3SO2Na (782 mg, 5.01 mmol) in H2O (5 mL), t-BuOOH (70% solution in H2O, 0.81 mL, 8.35 mmol) was slowly added at 0C. The reaction mixture was then warmed up to room temperature. After being stirred for 3 h, the reaction mixture was concentrated in vacuo. The crude residue was purified by column chromatography (CHCl3-MeOH=10 : 1 to 5 : 1) to give compound 2 as a white solid (264 mg, 59%). The NMR spectral data were identical to those reported in the literature.19)
  • 37
  • [ 57190-17-7 ]
  • [ 2926-29-6 ]
  • 2-bromo-1,3-diisopropyl-5-(trifluoromethyl)benzene [ No CAS ]
  • 38
  • [ 17217-57-1 ]
  • [ 2926-29-6 ]
  • 4,4'-dimethoxy-5-(trifluoromethyl)-2,2'-bipyridine [ No CAS ]
  • 39
  • [ 238098-26-5 ]
  • [ 2926-29-6 ]
  • 4-heptafluoroisopropyl-2-methyl-6-trifluoromethylaniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
19.5 g With tert.-butylhydroperoxide; iron(II) sulfate; In water; acetonitrile; at 34℃; for 5.5h;Inert atmosphere; 11077] In a 1000 ml three-neck flask, 25 g (91 mmol) of<strong>[238098-26-5]4-heptafluoroisopropyl-2-methylaniline</strong> were added to a mixture of 363.4 ml of water and 181.7 ml of acetonitrile. Then 27.3 ml (27.3 mmol) of aqueous 1 molar iron(II) sulphate solution and 31.19 g (200 mmol) of sodium trifluoromethylsulphinate were added. The mixture was blanketed with argon and then 35.1 g (273 mmol) of a 70percent aqueous tert-butyl hydroperoxide solution were metered in with a syringe pump within 4.5 hours without cooling. The temperature rose to 34° C. Afier the addition had ended, stirring was continued for another 1 hout For workup, the mixture was poured onto 425 ml of saturated aqueous sodium hydrogensulphite solution and stirred for 15 minutes. Then 425 ml of saturated sodium hydrogen carbonate solution were added and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed first with water and then with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. The crude product was chromatographed in two portions using a cartridge containing 120 g of silica gel and a cyclohexane/ethyl acetate gradient of 95:5 to 85:15 (v/v). 19.5 g of 4-heptafluoroisopropyl-2-methyl-6-trifluorometh- ylaniline were obtained.11078] HpLCMSa): log P=4.6711079] GC/MS: mass (mlz)=343, retention time: 2.98 mm, Kovats index: 108911080] (Agilent 6890 GC, HP5979 MSD, 10 m DR-i, iD=0.18 mm, FILM=0.4 tm, Inj.:250° C., const. flow: 1.6 nmilmin He, Det.:MSD:280° C., FID: 320° C., Oven:50° C. (1 min)-40° C./min-320° C. (3.25 mm))11081] ?H NMR (AV400, 400 MHz, d3-acetonitrile): oe (ppm)=7.50 (s, 1H), 7.48 (s, 1H), 5.03 (s, 2H, broad), 2.23 (s, 3H).
19.5 g With tert.-butylhydroperoxide; iron(II) sulfate; In water; acetonitrile; at 34℃;Inert atmosphere; In 1000ml three-necked flask, 25g (91mmol) 4- heptafluoro-isopropyl-2-methylaniline was added to a mixture of 181.7ml 363.4ml of water and acetonitrile.Followed by addition of 27.3ml (27.3mmol) 1 mole of iron sulfate (II) solution and 31.19g (200mmol) trifluoromethanesulfinic sodium.The mixture was then evacuated with argon, under without cooling, using a syringe pump 4.5 hours 35.1g (273mmol) 70percent tertiary butyl strength aqueous hydrogen peroxide metered injection.The temperature rose to 34 .After completion of the addition, the mixture was further stirred for 1 hour.In the latter treatment, the mixture was poured into 425ml of saturated aqueous sodium hydrogen sulfate and stirred for 15 minutes.Followed by addition of 425ml saturated aqueous sodium bicarbonate, the mixture was extracted three times with ethyl acetate.The combined organic phases were washed first with water, then washed with saturated aqueous sodium chloride, dried over sodium sulfate, and was concentrated under reduced pressure in a rotary evaporator.The crude product was fastened to cassettes containing 120g silica gel, using cyclohexane / ethyl acetate 95: 5 to 85:15 (v / v) gradient chromatography into two parts.This give 19.5g 4- heptafluoro-isopropyl-2-methyl-6-trifluoromethyl aniline.
19.5 g With tert.-butylhydroperoxide; iron(II) sulfate; In water; acetonitrile; at 34℃; for 5.5h;Inert atmosphere; Process 2 Example 4-heptafluoroisopropyl-2-methyi-6-trifluoromethyaniline D-1a in a 1000 ml three -neck flask, 25 g (91 mmol) of <strong>[238098-26-5]4-heptafluoroisopropyl-2-methylaniline</strong> were added to a mixture of 363.4 ml of water and 181.7 ml of acetonitrile. Then 27.3 ml (27.3 mmol) of aqueous 1 molar iron(II) sulphate solution and 31.19 g (200 mmol) of sodium trifluoromethylsulphinate were added. The mixture was blanketed with argon and then 35.1 g (273 mmol) of a 70percent aqueous tert-butyl hydroperoxide solution were metered in with a syringe pump within 4.5 hours without cooling. The temperature rose to 34°C. After the addition had ended, stirring was continued for another 1 hour. For workup, the mixture was poured onto 425 ml of saturated aqueous sodium hydrogensulphite solution and stirred for 15 minutes. Then 425 ml of saturated sodium hydrogen carbonate solution were added and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed first with water and then with saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated on a rotary evaporator under reduced pressure. The crude product was chromatographed in two portions using a cartridge containing 120 g of silica gel and a eye lohexane/ethyl acetate gradient of 95:5 to 85:15 (v/v). 19.5 g of 4-heptafluoroisopropyl-2-methyl-6- trifluoromethylaniline were obtained. HPLC-MS"': logP GC/MS: mass (m/z) = 343, retention time: 2.98 min, Kovats index: 1089 (Agilent 6890 GC, HP5979 MSD, 10m DB-i, iD=0.18mm, FILM=0^m, Inj.:250°C, const, flow: 1.6mm/min He, Det.:MSD:280°C, FID: 320°C, Oven:50°C(l min) - 40°C/min - 320°C (3.25 min)) NMR (AV400, 400 MHz, d3-acetonitrile): delta (ppm) = 7.50 (s, 1 H), 7.48 (s, 1H), 5.03 (s, 2H, broad), 2.23 (s, 3 H).
  • 40
  • [ 358-23-6 ]
  • [ 1625-91-8 ]
  • [ 2926-29-6 ]
  • 3,7-di-tert-butyl-S-(trifluoromethyl)dibenzothiophenium trifluoromethanesulfonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% In nitromethane; at 20℃; for 19.3333h;Inert atmosphere; Cooling with ice; A reactor (a round-bottomed flask) was charged with 6.44g (41.3 mmol) of dried sodium trifluoromethanesulfinate, 5.0 g (18.8mmol) of 4,4?-di-tert-butylbiphenyl, and 25 mL of dry nitromethane. The reactor was purged with N2 gas and cooled on an ice bath. Into the stirred mixture, 12.7 g (45.0 mmol) of trifluoromethanesulfonic anhydridewas drop-wise addedfor 20 mm. The reaction mixture was gradually warmed to room temperature and stirred at room temperature for 19 hours. ?9FNMR analysis of the reaction solution using benzotrifluoride as a standard showed that the product, 3,7-di-tert-butyl-S- (trifluoromethyl)dibenzothiophenium trifluoromethanesulfonate, was produced in 87percent yield. After the reaction solution was evaporated to dryness, 25 mL of toluene was added and evaporated up. This evaporation process of toluene was repeated three times to completely remove the nitromethane solvent. Into the residue, 35m1 of water and 35m1 of diethyl ether were added and the mixture was stirred for about 1 hour. The resulting precipitates were collected by filtration, giving 8.3 g (86percent yield) of pure 3,7- di-tert-butyl-S-(trifluoromethyl)dibenzothiophenium trifluoromethanesulfonate as crystalline solid. The spectral analysis of this product proved the assigned chemical structure. The physical and spectral data are shown as follows: Decomposition-starting point 211 °C (by TGA/DSC);?H NMR (400.2 MHz, DMSO-d6) 8.75 (2H, d, 1=1.7 Hz, 4,6-H), 8.41 (2H, d, 1=8.3 Hz, 1,9-H), 8.09 (2H, dd, 1=1.7, 8.3 Hz, 2,8-H), 1.39 (18H, s, tert-Bu); ?9F NMR (376.5 MHz, DMSO-d6) -54.13 (3F, s, CF3), -77.75 (3F, s, SO2CF3).
  • 41
  • [ 1493-13-6 ]
  • [ 1625-91-8 ]
  • [ 2926-29-6 ]
  • 3,7-di-tert-butyl-S-(trifluoromethyl)dibenzothiophenium trifluoromethanesulfonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% A reactor (a round-bottomed flask) was charged with 3.8g (24.4mol) of dried sodium trifluoromethanesulfinate, 5.0 g (18.8mmol) of 4,4?-di-tert-butylbiphenyl, and 25 mL of dry nitromethane. The reactor was purged with N2 gas. Into the stirred mixture, 9.9 g (47.0 mmol) of trifluoroacetic anhydridewas drop-wise addedfor 10 mm, and the mixture was stirred for 1.5 hours. Trifluoromethanesulfonic acid (7.1 g, 47.0 mmol) was then added slowly in a period of about 15 mm so that the temperature of the reaction mixture did not exceed 25 °C under cooling with an ice bath.After the addition, the benzotrifluoride as a reaction mixture was stirred for 30 mm on an ice bath and then the bath was removed. The mixture was then stirred at room temperature for 22 hours. ?9FNMR analysis of the reaction solution using standard showed that the product, 3,7-di-tert-butyl-S- (trifluoromethyl)dibenzothiophenium trifluoromethanesulfonate, was produced in 51percent yield. After the reaction solution was evaporated to dryness, 25 mL of toluene was added and evaporated to dryness. The evaporation process of toluene was repeated three times. Into the residue, were added 35m1 of water and 35m1 of diethyl ether, and then the mixture was stirred for about 60 mm. The resulting precipitates were collecting by filtration, giving 4.8 g (50percent yield) of pure 3,7-di-tert-butyl-S- (trifluoromethyl)dibenzothiophenium trifluoromethanesulfonate as crystalline solid. The spectral data agreed with those of an authentic sample.
  • 42
  • [ 637-89-8 ]
  • [ 2926-29-6 ]
  • [ 461-84-7 ]
YieldReaction ConditionsOperation in experiment
72% With dipotassium peroxodisulfate; silver nitrate; In water; acetonitrile; at 80℃; for 24h;Inert atmosphere; General procedure: A reaction tube was charged with 4-methylbenzenethiol (1b) (24.8 mg, 0.2 mmol) at room temperature, then trifluoromethanesulfinate (62.4 mg, 0.4 mmol), silver nitrate (3.4 mg, 0.02 mmol), potassium persulfate (108 mg, 0.4 mmol) and MeCN/H2O (1:1, 0.8 mL) were added. The resulting mixture was stirred at 80 under argon atmosphere for 24 h. After cooling to room temperature, the reaction mixture was quenched and purified by flash silica gel column chromatography (eluent: petroleum ether/EtOAc) to afford the desired product 3b (23.0 mg, 60%).
  • 43
  • [ 2926-29-6 ]
  • [ 95-50-1 ]
  • [ 328-84-7 ]
  • [ 54773-19-2 ]
  • 44
  • [ 2926-29-6 ]
  • [ 100-47-0 ]
  • [ 368-77-4 ]
  • [ 455-18-5 ]
  • [ 447-60-9 ]
  • 45
  • [ 2926-29-6 ]
  • [ 108-88-3 ]
  • [ 6140-17-6 ]
  • [ 401-79-6 ]
  • [ 13630-19-8 ]
  • 46
  • [ 2926-29-6 ]
  • [ 174775-48-5 ]
  • ethyl 5-isothiocyanatobenzofuran-2-carboxylate [ No CAS ]
  • 47
  • [ 51792-34-8 ]
  • [ 2926-29-6 ]
  • 3,4-dimethoxy-2-(trifluoromethyl)thiophene [ No CAS ]
  • 48
  • [ 2926-29-6 ]
  • [ 93247-78-0 ]
  • 3-trifluoromethylsulfanyl-7,1H-indolecarboxylic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With N-chlorophthalimide; triphenylphosphine; eosin y; In acetonitrile; at 20℃; for 6h;Inert atmosphere; Schlenk technique; Irradiation; 10 mL of Schlenk tube was added Eosin Y (0.01 mmol), sodium trifluoromethanesulfinate (0.3 mmol), triphenylphosphine(0.6 mmol), N-chlorophthalimide (0.3 mmol), evacuated and washed into dry nitrogen (this procedure was repeated three times)7-methylindole (0.2 mmol) was dissolved in the ultra-dry solvent acetonitrile and the resulting solution was passed through a syringe into a Schlenk tube. Room temperature, The reaction was allowed to stand under a white LED lamp and stirred for 6 hours. After completion of the reaction, the solvent was evaporated and the residue was passed through the residuePurification by silica gel column chromatography gave 33 mg of product, yield 60percent.
  • 49
  • [ 2926-29-6 ]
  • [ 106-49-0 ]
  • [ 6140-17-6 ]
  • 50
  • [ 462-08-8 ]
  • [ 2926-29-6 ]
  • [ 3796-23-4 ]
  • 51
  • [ 2926-29-6 ]
  • [ 5203-77-0 ]
  • 1,3-dimethyl-4-((trifluoromethyl)thio)-1H-pyrazol-5-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With Dichlorophenylphosphine; In 1,4-dioxane; at 60 - 70℃; for 3h;Schlenk technique; General procedure: To a flame-dried Schlenk tube was added electron-rich aromatic (0.5mmol), CF3SO2Na (118mg, 0.7mmol) dry 1,4-dioxane or CH3CN (1mL). The mixture was heated to 60C by a preheated oil bath. PhPCl2 (125mg, 0.7 mmoL) was added. The reaction mixture was stirred at 70C for the indicated time. Then the reaction mixture was cooled to room temperature. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to afford the pure product.
  • 52
  • [ 2926-29-6 ]
  • [ 2382-79-8 ]
  • N-acetyl-2-trifluoromethyl-L-tryptophanamide [ No CAS ]
  • 53
  • [ 2926-29-6 ]
  • [ 485-71-2 ]
  • (R)-((1S,2S,4S,5R)-5-((R)-1-chloro-3,3,3-trifluoropropyl)quinuclidin-2-yl)(quinolin-4-yl)methanol [ No CAS ]
  • C20H22ClF3N2O [ No CAS ]
  • 54
  • [ 1034287-04-1 ]
  • [ 2926-29-6 ]
  • (E)-2-(4-(1-chloro-3,3,3-trifluoroprop-1-en-1-yl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ No CAS ]
  • (Z)-2-(4-(1-chloro-3,3,3-trifluoroprop-1-en-1-yl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ No CAS ]
  • 55
  • [ 3752-25-8 ]
  • [ 2926-29-6 ]
  • 1-(2-chlorophenyl)-2-((trifluoromethyl)thio)ethanone [ No CAS ]
  • 56
  • [ 79128-08-8 ]
  • [ 2926-29-6 ]
  • 1,3-diisopropoxy-2-(trifluoromethyl)benzene [ No CAS ]
  • 1,3-diisopropoxy-4-(trifluoromethyl)benzene [ No CAS ]
  • 57
  • [ 4107-65-7 ]
  • [ 2926-29-6 ]
  • 2,4-dimethoxy-5-(trifluoromethyl)benzonitrile [ No CAS ]
  • C10H8F3NO2 [ No CAS ]
  • 58
  • [ 2489-86-3 ]
  • [ 2926-29-6 ]
  • 1-(2-azido-4,4,4-trifluorobutyl)naphthalene [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With tert.-butylhydroperoxide; trimethylsilylazide; manganese(III) triacetate dihydrate; In water; acetonitrile; at 45℃; for 12h;Inert atmosphere; Adding a catalyst manganese acetate (Mn(OAc)3·2H2O, 16.1 mg, to a 15 ml reaction tube,0.06 mmol, <strong>[2489-86-3]1-allyl naphthalene</strong> (50.5 mg, 0.3 mmol), followed by sodium trifluoromethylsulfinate(CF3SO2Na, 93.6 mg, 0.6 mmol), the pump was evacuated, filled with argon, repeated 3 times, azide trimethylsilane (118 micron)L, 0.9 mmol), t-butyl hydroperoxide (TBHP (70% in water), 124 mul, 0.9 mmol)The injector was added and 2 ml of acetonitrile was added using a syringe. Heat this mixture through an oil bath to 45 degrees Celsius in an argon ringStir for 12 hours. Then stop heating, cool to room temperature, spin off the solvent acetonitrile, and directly separate by column chromatography (petroleumEther) gave the product 41.9 mg in a total yield of 50%
  • 59
  • [ 2495-37-6 ]
  • [ 2926-29-6 ]
  • [ 1602485-37-9 ]
YieldReaction ConditionsOperation in experiment
42% With tert.-butylhydroperoxide; trimethylsilylazide; manganese(III) triacetate dihydrate; In water; acetonitrile; at 45℃; for 12h;Inert atmosphere; a catalyst of 1.5 ml was added to the catalyst manganese acetate (Mn(OAc)3·2H2O, 16.1 mg,0.06 mmol), additional sodium trifluoromethanesulfinate (CF3SO2Na, 93.6 mg, 0.6 mmol), vacuum pumped, argon-filled, repeated 3 times, <strong>[2495-37-6]benzyl methacrylate</strong> (51 mul, 0.3 Millimol), azide trimethylsilane(118 muL, 0.9 mmol), tert-butyl hydroperoxide (TBHP (70% in water), 124 mul, 0.9 mmol) was added separately using a micro-injector, and 2 ml of acetonitrile was added by syringe. The mixture was heated to 45 degrees Celsius by an oil bath.Stir under argon for 12 hours. Then stop heating, cool to room temperature, spin off the solvent acetonitrile, and directly use column chromatographyThe product was obtained from (petroleum ether) 36.2 mg, with a total yield of 42%.
  • 60
  • [ 700-06-1 ]
  • [ 2926-29-6 ]
  • [2-trifluoromethyl-(1H)-indol-3-yl]-methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
25% With 1,1,1,3',3',3'-hexafluoro-propanol; 2-tert-butylanthraquinine; ammonium carbonate; In acetonitrile; at 33℃; for 24h;Irradiation; Sealed tube; General procedure: The desired indole (0.3 mmol, 1 eq) was mixed with sodium trifluoromethylsulfinate (0.6 mmol, 2 eq), 2-tert-butyl anthraquinone (0.06 mmol, 0.2 eq), ammonium carbonate (0.18 mmol, 0.6 eq), hexafluoroisopropyl alcohol (0.075 mmol, 0.25 eq), and acetonitrile (3 mL, 0.1 M) in a quartz tube and irradiated at 255 nm for 24 hours. The reaction was quenched with water and extracted with DCM or EtOAc (3 x 30 mL). The combined organic layers were dried over sodium sulfate, and the solvent removed in vacuo. The desired product was then isolated using preparative TLC with the appropriate solvent system.
  • 61
  • [ 2926-29-6 ]
  • [ 82019-32-7 ]
  • [ 1225322-64-4 ]
YieldReaction ConditionsOperation in experiment
54% With bis-[(trifluoroacetoxy)iodo]benzene; In acetonitrile; at 20.0℃; for 12.0h;Inert atmosphere; Add the substrate <strong>[82019-32-7]1-methyl-7-bromoquinoxaline-2(1H)-one</strong> to a 15 ml reaction tube 71.7 mg, 0.3 mmol, the substituent on the structural formula R1 is a methyl group, and R2 is a bromine atom), Sodium trifluoromethylsulfinate (CF3SO2Na, 140.5 mg, 0.9 mmol), An oxidizing agent iodobenzene bis(trifluoroacetate) (387.0 mg, 0.9 mmol) was added. The oil pump was evacuated, filled with argon gas, and repeated 3 times, and 3 ml of acetonitrile was added by a syringe. The mixture was stirred at room temperature under an argon atmosphere for 12 hours. The reaction was confirmed to be completely complete by TLC. The solvent acetonitrile was distilled off and then directly purified by column chromatography (ethyl acetate / petroleum ether = 1/3) to give the produc 1-methyl-3-trifluoromethyl-7-bromoquinoxaline-2(1H)-one 49.8 mg, total yield 54%.
  • 62
  • [ 827-52-1 ]
  • [ 2926-29-6 ]
  • (4-cyclohexylphenyl)(trifluoromethyl)sulfane [ No CAS ]
  • 63
  • [ 827-52-1 ]
  • [ 2926-29-6 ]
  • 1-cyclohexyl-4-((trifluoromethyl)sulfinyl)benzene [ No CAS ]
  • 64
  • [ 41604-19-7 ]
  • [ 2926-29-6 ]
  • (4'-bromo-2'-fluoro[1,1'-biphenyl]-4-yl)(trifluoromethyl)sulfane [ No CAS ]
  • 65
  • [ 159-66-0 ]
  • [ 2926-29-6 ]
  • 9,9'-spirobi[fluoren]-2-yl(trifluoromethyl)thioether [ No CAS ]
  • 66
  • [ 15878-00-9 ]
  • [ 622-97-9 ]
  • [ 2926-29-6 ]
  • 4-chloro-1-(3,3,3-trifluoro-1-(p-tolyl)propyl)-1H-pyrazole [ No CAS ]
  • 67
  • C11H12 [ No CAS ]
  • [ 2926-29-6 ]
  • [ 5779-93-1 ]
  • 68
  • [ 637-69-4 ]
  • [ 29906-67-0 ]
  • [ 2926-29-6 ]
  • 1-methyl-5-nitro-3-(3,3,3-trifluoro-1-(4-methoxyphenyl)propyl)-1H-indole [ No CAS ]
  • 69
  • [ 637-69-4 ]
  • [ 5840-01-7 ]
  • [ 2926-29-6 ]
  • 1-(3,3,3-trifluoro-1-(4-methoxyphenyl)propyl)-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline [ No CAS ]
  • 70
  • [ 621-38-5 ]
  • [ 2926-29-6 ]
  • [ 833-15-8 ]
  • 71
  • [ 939-57-1 ]
  • [ 2926-29-6 ]
  • [ 1357615-52-1 ]
  • 72
  • [ 779-89-5 ]
  • [ 2926-29-6 ]
  • [ 78622-59-0 ]
  • 73
  • [ 14473-91-7 ]
  • [ 2926-29-6 ]
  • [ 1559077-94-9 ]
  • 74
  • [ 3752-25-8 ]
  • [ 2926-29-6 ]
  • [ 78622-60-3 ]
  • 75
  • [ 2316-26-9 ]
  • [ 2926-29-6 ]
  • [ 1418317-22-2 ]
  • 76
  • [ 2495-37-6 ]
  • [ 2926-29-6 ]
  • benzyl 4,4,4-trifluoro-2-hydroxy-2-methylbutanoate [ No CAS ]
  • 77
  • [ 4107-65-7 ]
  • [ 2926-29-6 ]
  • 2,4-dimethoxy-5-(trifluoromethyl)benzonitrile [ No CAS ]
  • 78
  • [ 2926-29-6 ]
  • [ 108831-66-9 ]
  • [ 106691-21-8 ]
  • 79
  • [ 1455-20-5 ]
  • [ 2926-29-6 ]
  • 2-butyl-5-(trifluoromethyl)thiophene [ No CAS ]
  • C10H10F6S [ No CAS ]
  • 80
  • [ 876919-08-3 ]
  • [ 2926-29-6 ]
  • methyl 2-trifluoromethyl-3-fluoro-4-pyridinecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tert.-butylhydroperoxide; In dichloromethane; water; at 20℃; for 12h; In a 5L three-neck reaction flask, add 1.25L of methylene chloride,500mL water and compound of formula (V)3-fluoro-4-picolinic acid methyl ester (250g, 1.0eq)After stirring well, add 250mL tert-butoxy peroxybutanol and 360gSodium trifluoromethylsulfinate (5.0eq). The mixture was stirred at room temperature for 12 hours to monitor the completion of the reaction.The methylene chloride solvent was carefully removed at room temperature, and the residue was carefully added to crushed ice, stirred well, and extracted twice with diethyl ether. After washing the combined organic phase with ice water three times, the organic phase was dried and concentrated at low temperature, and the obtained product (VI) was directly put into the next reaction.
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