2-Hydroxy-6-(trifluoromethyl)pyridine (HTF) - Huimeng Bio-tech

2-Hydroxy-6-(trifluoromethyl)pyridine (HTF)

CAS NO.: -06-1 

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Capacity T/Y:  

Assay: ≥ 99%

Molecular formula: C6H4F3NO

Molecular weight: 163.1

Appearance shape: white crystal

Properties of 2-Hydroxy-6-(trifluoromethyl)pyridine (HTF)

Density: 1.4±0.1 g/cm3

Boiling point: 265.6±35.0 °C at 760 mmHg

Flash point: 114.4±25.9 °C

Exact mass: 163.

PSA: 32.

LogP: 1.23

Appearance: off-white powder)

Vapor pressure: 0.0±0.6 mmHg at 25°C

Refractive index: 1.457

Storage conditions: stored under room temperature.

Applicayion of 2-Hydroxy-6-(trifluoromethyl)pyridine

Pharmaceutical Applications
Versatile Intermediate: 2-Hydroxy-6-(trifluoromethyl)pyridine is a valuable intermediate in the synthesis of complex organic molecules, including active pharmaceutical ingredients (APIs). Its unique structure allows it to be used in the production of drugs with specific properties, such as increased bioavailability or improved pharmacokinetics.The trifluoromethyl group in 2-Hydroxy-6-(trifluoromethyl)pyridine can enhance the lipophilicity of pharmaceutical compounds, potentially improving their ability to penetrate biological membranes and increasing their effectiveness.

Agrochemical Applications
Selective Herbicide Production: 2-Hydroxy-6-(trifluoromethyl)pyridine is used in the synthesis of selective herbicides, providing targeted control of unwanted plant species without harming crops. Its chemical properties help in creating herbicides that are more effective at lower doses, reducing the environmental impact. The trifluoromethyl group contributes to the thermal and chemical stability of pesticides, extending their shelf life and efficacy in various environmental conditions.

Safety Statement of 2-Hydroxy-6-(trifluoromethyl)pyridine (HTF)

Symbol(GHS) 
         GHS07             GHS08 Signal word  Warning Hazard statements  H315-H319-H341 Precautionary statements  P501-P202-P201-P264-P280-P302+P352-P308+P313-P337+P313-P305+P351+P338-P362+P364-P332+P313-P405 Hazard Codes  T, Xi Risk Statements  36/37/38-36-25 Safety Statements  26-36/37/39-45 RIDADR  HazardClass  IRRITANT PackingGroup  Ⅲ

2-Hydroxy-6-(trifluoromethyl)pyridine is a versatile compound with significant advantages in pharmaceuticals, agrochemicals, materials science, and chemical synthesis. Its unique chemical properties enable the development of advanced products with enhanced performance, stability, and environmental safety.

以下实施例有助于理解本发明，但不限于本发明的内容The following examples help to understand the present invention, but are not limited to the content of the present invention

                          实施例1Example 1

If you want to learn more, please visit our website 2-Chloro-6-trichloromethyl pyridine.

                 2-羟基-4-三氟甲基吡啶的制备 Preparation of 2-Hydroxy-4-trifluoromethylpyridine

通氮气保护，搅拌下，将1.5mol锌粉加到500ml四氢呋喃溶液中，然后滴加0.1mol三甲基氯硅烷，加热至回流，活化0.5h，停止加热后，滴加化合物1.0mol 1，1，1-三氟-4-烷氧基-3-丁烯-2-酮和1.1mol氯乙腈的四氢呋喃的混合溶液，滴加完毕后回流3h，停止加热，滴加400ml浓盐酸，再回流2h，冷却至室温，10％氢氧化钠中和，水相用乙酸乙酯萃取，合并有机相，无水硫酸钠干燥，浓缩，所得粗品再用氯仿重结晶，得到130.2g 2-羟基-4-三氟甲基吡啶，收率80％。Under nitrogen protection, under stirring, add 1.5mol zinc powder to 500ml tetrahydrofuran solution, then dropwise add 0.1mol trimethylchlorosilane, heat to reflux, activate for 0.5h, stop heating, dropwise add compound 1.0mol 1,1 , a mixed solution of 1-trifluoro-4-alkoxy-3-buten-2-one and 1.1mol chloroacetonitrile in tetrahydrofuran, reflux for 3h after the dropwise addition, stop heating, add 400ml of concentrated hydrochloric acid dropwise, and then reflux for 2h , cooled to room temperature, neutralized with 10% sodium hydroxide, the aqueous phase was extracted with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and the resulting crude product was recrystallized with chloroform to obtain 130.2g 2-hydroxyl-4- Trifluoromethylpyridine, yield 80%.

IR v(cm-1)：(N-II)，，(C＝0)，，(CF3)IR v (cm -1 ): (N-II), , (C=0), , (CF 3 )

1HNMR(CDCl3)：δ6.49(dd，1H，J＝1.6，6.9Hz)，6.78(d，1H，J＝0.85Hz)，7.75(d，1H，J＝7.0Hz)； 1 HNMR (CDCl 3 ): δ6.49 (dd, 1H, J=1.6, 6.9Hz), 6.78 (d, 1H, J=0.85Hz), 7.75 (d, 1H, J=7.0Hz);

MS(70eV)，m/e(relative intensity)：163(M+，100)，144(M+，12)，135(83)，116(99)，85(25)，69(CF3，15)，57(15)，43(15).MS (70eV), m/e (relative intensity): 163 (M + , 100), 144 (M + , 12), 135 (83), 116 (99), 85 (25), 69 (CF 3 , 15 ), 57(15), 43(15).

                         实施例2Example 2

                  2-氯-4-三氟甲基吡啶的制备Preparation of 2-chloro-4-trifluoromethylpyridine

室温下，将1.0mol 2-羟基-4-三氟甲基吡啶加到160mlDMF中，然后再加入2.0mol五氯化磷，反应5h，反应完全后，再进行减压蒸馏，收集78-80℃/75mmHg馏分，得到152.5g 2-氯-4-三氟甲基吡啶，收率为84.3％。At room temperature, add 1.0mol 2-hydroxy-4-trifluoromethylpyridine to 160ml DMF, then add 2.0mol phosphorus pentachloride, react for 5h, after the reaction is complete, carry out vacuum distillation, collect 78-80℃ /75mmHg fraction, obtain 152.5g 2-chloro-4-trifluoromethylpyridine, yield is 84.3%.

19FNMR-13(S，CF3)：-11.5ppm(TFA)； 19 FNMR-13 (S, CF 3 ): -11.5ppm (TFA);

MS(70eV)，m/e(relative intensity)：181(M+，3.58)，146(M+-C1,100)，69(CF3，54)，126(25).MS (70eV), m/e (relative intensity): 181 (M + , 3.58), 146 (M + -C1, 100), 69 (CF 3 , 54), 126 (25).

                        实施例3Example 3

                 2-氯-4-三氟甲基吡啶的制备Preparation of 2-chloro-4-trifluoromethylpyridine

通氮气保护，搅拌下，将1.5mol锌粉加到500mlN，N-二甲基甲酰胺溶液中，然后滴加0.005mol三甲基氯硅烷，加热至60℃，活化0.5h，停止加热后，滴加化合物1mol 1，1，1一三氟-4一烷氧基-3-丁烯一2一酮和1.1mol氯乙腈的N，N-二甲基甲酰胺的混合溶液，滴加完毕后回流3h，停止加热，冷却至室温，然后向该体系中通干燥的氯化氢气体，反应完全后，倒入冰水中，用乙酸乙酯萃取，合并有机相，无水硫酸钠干燥，浓缩，减压蒸馏，收集78-80℃/75mmHg馏分，得到80.7g 2-氯-4-三氟甲基吡啶，收率44％。Under nitrogen protection, under stirring, add 1.5mol zinc powder to 500ml N,N-dimethylformamide solution, then dropwise add 0.005mol trimethylchlorosilane, heat to 60°C, activate for 0.5h, stop heating, Add dropwise the mixed solution of N,N-dimethylformamide of compound 1mol 1,1,1-trifluoro-4-alkoxy-3-butene-2-ketone and 1.1mol chloroacetonitrile, after the dropwise addition is completed Reflux for 3 hours, stop heating, cool to room temperature, and then pass dry hydrogen chloride gas into the system. After the reaction is complete, pour into ice water, extract with ethyl acetate, combine organic phases, dry over anhydrous sodium sulfate, concentrate, and reduce pressure After distillation, the 78-80°C/75mmHg fraction was collected to obtain 80.7g of 2-chloro-4-trifluoromethylpyridine, with a yield of 44%.

                        实施例4Example 4

                 2-氯-4-三氟甲基吡啶的制备Preparation of 2-chloro-4-trifluoromethylpyridine

通氮气保护，搅拌下，将1.5mol锌粉加到500mlN，N-二甲基甲酰胺溶液中，然后滴加0.005mol三甲基氯硅烷，加热至60℃，活化0.5h，停止加热后，滴加化合物1mol 1，1，1一三氟-4一烷氧基-3-丁烯一2一酮和1.1mol氯乙腈的N，N-二甲基甲酰胺的混合溶液，滴加完毕后回流3h，停止加热，冷却至室温。将此反应液滴加到含有1.1mol五氯化磷的N，N-二甲基甲酰胺的混合溶液中，然后向该体系中通干燥的氯化氢气体，反应完全后，倒入冰水中，用乙酸乙酯萃取，合并有机相，无水硫酸钠干燥，浓缩，减压蒸馏，收集78-80℃/75mmHg馏分，得到110.7g 2-氯-4-三氟甲基吡啶，收率61.5％。Under nitrogen protection, under stirring, add 1.5mol zinc powder to 500ml N,N-dimethylformamide solution, then dropwise add 0.005mol trimethylchlorosilane, heat to 60°C, activate for 0.5h, stop heating, Add dropwise the mixed solution of N,N-dimethylformamide of compound 1mol 1,1,1-trifluoro-4-alkoxy-3-butene-2-ketone and 1.1mol chloroacetonitrile, after the dropwise addition is completed Reflux for 3h, stop heating, and cool to room temperature. Add this reaction solution dropwise to the mixed solution of N,N-dimethylformamide containing 1.1mol phosphorus pentachloride, then pass dry hydrogen chloride gas into the system, after the reaction is complete, pour it into ice water, and use Extract with ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, concentrate, and distill under reduced pressure, collect 78-80°C/75mmHg fractions to obtain 110.7g of 2-chloro-4-trifluoromethylpyridine with a yield of 61.5%.

                         实施例5Example 5

实验步骤同实施例3、实施例4，所不同的是反应物，反应条件和结果见下表：Experimental procedure is with embodiment 3, embodiment 4, and difference is reactant, and reaction condition and result see the following table:

第一步反应结果：   序号    1，1，1-三氟-4-烷氧基-3-烷基丁烯-2-酮    2-卤代烷基腈          第一步反应条件       原料摩尔比*  R1  R3 R2  X   1  CH3  苯基 H  Cl  Zn/DMSO/(CH3)3SiCl/60℃  1∶1∶1.5∶0.01   2  C2H5  吡啶基 H  Br  Mg/THF/(CH3)3SiBr/80℃  1∶1.5∶2∶0.02   3  C3H7  CH3 C4H11  I  Zn-Ag/HMPA/(C2H5)3SiCl/50℃  1∶2∶1∶0.005   4  CH3  呋喃基 CH3  Cl  Zn-Cu/DMF/(C2H5)3SiBr/75℃  1∶2∶2∶0.02   5  C4H11  H 苯基  I  Zn/苯/(CH3)3SiCl/65℃     1∶1.5∶1.5∶0.015   6  H  苄基 CH3  Br  Zn/二甲苯/(CH3)3SiCl/70℃  1∶1∶2∶0.02   7  CH3  CH3 吡啶基  Br  Zn-Ag/甲苯/(C2H5)3SiCl/80℃  1∶1∶1.5∶0.02   8  C2H5  2-甲基吡啶 H  Br  Zn-Cu/DMSO/(C2H5)3SiBr/77℃  1∶2∶1.8∶0.015   9  C3H7  H 呋喃基  I  Zn/DMF/(C2H5)3SiBr/68℃  1∶2∶2∶0.015   10  CH3  C4H11 C2H5  Cl  Zn-Ag/HMPA/(C2H5)3SiCl/72℃  1∶1∶1∶0.01   11  C4H11  CH3 H  Cl  Zn/THF/(CH3)3SiCl/64℃     1∶1.2∶1.2∶0.02   12  H  C3H7 CH3  Cl  Mg/苯/(CH3)3SiBr/60℃  1∶1∶1.5∶0.015   13  CH3  H H  Cl  Zn-Cu/DMSO/(C2H5)3SiBr/57℃  1∶2∶1∶0.015   14  C2H5  苯基 H  I  Zn/DMF/(C2H5)3SiBr/60℃  1∶2∶2∶0.005   15  C3H7  H H  Br  Zn-Ag/HMPA/(C2H5)3SiCl/55℃  1∶1.5∶1∶0.01   16  CH3  H H  Br  Zn/THF/(CH3)3SiCl/74℃     1∶1∶1.2∶0.02   17  C4H11  H H  Br  Mg/苯/(CH3)3SiBr/66℃  1∶2∶1.5∶0.015 The result of the first step reaction: serial number 1,1,1-Trifluoro-4-alkoxy-3-alkylbuten-2-one 2-haloalkylnitrile First step reaction conditions Raw material molar ratio* R1 R3 R2 x 1 CH3 Phenyl h Cl Zn/DMSO/(CH 3 ) 3 SiCl/60℃ 1:1:1.5:0.01 2 C 2 H 5 pyridyl h Br Mg/THF/(CH 3 ) 3 SiBr/80℃ 1:1.5:2:0.02 3 C 3 H 7 CH3 C 4 H 11 I Zn-Ag/HMPA/(C 2 H 5 ) 3 SiCl/50℃ 1:2:1:0.005 4 CH3 furyl CH3 Cl Zn-Cu/DMF/(C 2 H 5 ) 3 SiBr/75℃ 1:2:2:0.02 5 C 4 H 11 h Phenyl I Zn/Benzene/(CH 3 ) 3 SiCl/65℃ 1:1.5:1.5:0.015 6 h Benzyl CH3 Br Zn/Xylene/(CH 3 ) 3 SiCl/70℃ 1:1:2:0.02 7 CH3 CH3 pyridyl Br Zn-Ag/Toluene/(C 2 H 5 ) 3 SiCl/80℃ 1:1:1.5:0.02 8 C 2 H 5 2-Methylpyridine h Br Zn-Cu/DMSO/(C 2 H 5 ) 3 SiBr/77℃ 1:2:1.8:0.015 9 C 3 H 7 h furyl I Zn/DMF/(C 2 H 5 ) 3 SiBr/68℃ 1:2:2:0.015 10 CH3 C 4 H 11 C 2 H 5 Cl Zn-Ag/HMPA/(C 2 H 5 ) 3 SiCl/72℃ 1:1:1:0.01 11 C 4 H 11 CH3 h Cl Zn/THF/(CH 3 ) 3 SiCl/64℃ 1:1.2:1.2:0.02 12 h C 3 H 7 CH3 Cl Mg/Benzene/(CH 3 ) 3 SiBr/60℃ 1:1:1.5:0.015 13 CH3 h h Cl Zn-Cu/DMSO/(C 2 H 5 ) 3 SiBr/57℃ 1:2:1:0.015 14 C 2 H 5 Phenyl h I Zn/DMF/(C 2 H 5 ) 3 SiBr/60℃ 1:2:2:0.005 15 C 3 H 7 h h Br Zn-Ag/HMPA/(C 2 H 5 ) 3 SiCl/55℃ 1:1.5:1:0.01 16 CH3 h h Br Zn/THF/(CH 3 ) 3 SiCl/74℃ 1:1:1.2:0.02 17 C 4 H 11 h h Br Mg/Benzene/(CH 3 ) 3 SiBr/66℃ 1:2:1.5:0.015

注：*：1，1，1-三氟-4-烷氧基-3-烷基丁烯-2-酮∶2-卤代烷基腈∶金属试剂∶三烷基卤代硅烷的摩尔比Note: *: Molar ratio of 1,1,1-trifluoro-4-alkoxy-3-alkylbutene-2-one:2-haloalkylnitrile:metal reagent:trialkylhalosilane

第二步反应结果：  序号  PX5和/或HCl   有机溶剂 摩尔比#                    产物  得率 R2 R3 R4 R5  1  PCl5 二氯乙烷 1∶2 H 苯基 Cl  H   80  2  PCl5 二氯乙烷 1∶2.5 H 吡啶基 Cl  H   75  3  PCl5 二氯乙烷 1∶1.5 C4H9 CH3 Cl  H   85  4  HCl DMF 1∶4 CH3 呋喃基 Cl  H   54  5  PCl5 四氯化碳 1∶1.2 苯基 H Cl  H   65  6  PCl5 二氯甲烷 1∶4 CH3 苯基 Cl  H   70  7  PCl5 氯仿 1∶3 吡啶基 CH3 Cl  H   77  8  PCl5 四氯化碳 1∶4 H 2-甲基吡啶 Cl  H   66  9  HCl DMF 1∶3.5 呋喃基 H Cl  H   45  10  PCl5 二氯甲烷 1∶2 C2H5 C4H9 Cl  H   87  11  PCl5 四氯化碳 1∶2.5 H CH3 Cl  H   76  12  PCl5 氯仿 1∶1.5 CH3 C3H7 Cl  H   83  13  PBr5 二氯乙烷 1∶1.5 H H Br  H   90  14  PBr5 二氯乙烷 1∶2 H 苯基 Br  H   77  15  PCl5     / 1∶4 H H Cl  Cl   55  16  PCl5 DMF 1∶1 H H Cl  OC2H5   44  17  P/I2 二氯乙烷 1∶2 H H I  H   57 The result of the second step reaction: serial number PX 5 and/or HCl Organic solvents The molar ratio of# product Yield R2 R3 R4 R5 1 PCl 5 Dichloroethane 1:2 h Phenyl Cl h 80 2 PCl 5 Dichloroethane 1:2.5 h pyridyl Cl h 75 3 PCl 5 Dichloroethane 1:1.5 C 4 H 9 CH3 Cl h 85 4 HCl DMF 1:4 CH3 furyl Cl h 54 5 PCl 5 carbon tetrachloride 1:1.2 Phenyl h Cl h 65 6 PCl 5 Dichloromethane 1:4 CH3 Phenyl Cl h 70 7 PCl 5 Chloroform 1:3 pyridyl CH3 Cl h 77 8 PCl 5 carbon tetrachloride 1:4 h 2-Methylpyridine Cl h 66 9 HCl DMF 1:3.5 furyl h Cl h 45 10 PCl 5 Dichloromethane 1:2 C 2 H 5 C 4 H 9 Cl h 87 11 PCl 5 carbon tetrachloride 1:2.5 h CH3 Cl h 76 12 PCl 5 Chloroform 1:1.5 CH3 C 3 H 7 Cl h 83 13 PBr 5 Dichloroethane 1:1.5 h h Br h 90 14 PBr 5 Dichloroethane 1:2 h Phenyl Br h 77 15 PCl 5 / 1:4 h h Cl Cl 55 16 PCl 5 DMF 1:1 h h Cl OC 2 H 5 44 17 P/I 2 Dichloroethane 1:2 h h I h 57

注：#：中间产物烯丙醇∶HCl或PX5的摩尔比Note: #: Molar ratio of intermediate product allyl alcohol: HCl or PX 5

                        实施例6Example 6

2-巯基-4-三氟甲基吡啶的制备Preparation of 2-mercapto-4-trifluoromethylpyridine