单/二/三氟甲氧基化试剂的制备方法的研究进展

doi:10.6023/cjoc202403011

摘要/Abstract

含氟有机分子在制药、农业化学和材料科学领域具有广泛应用. 在制药领域, 引入含氟甲氧基基团可提高药物的生物利用度、代谢稳定性, 并调控分子的立体化学和电子结构, 从而改善药物疗效和选择性; 在农业领域, 含氟有机化合物具有防虫和杀菌作用; 在材料科学中, 含氟甲氧基化合物因其优异的电化学性能和热稳定性, 广泛应用于电池、涂层和催化剂的合成与改性. 因此, 如何高效地引入含氟甲氧基基团成为有机化学领域的研究热点. 对单氟甲氧基(OCH₂F)、二氟甲氧基(OCF₂H)、三氟甲氧基(OCF₃)试剂的制备方法以及三氟甲氧基试剂的发展进行了综述.

关键词: 单氟甲氧基试剂, 二氟甲氧基试剂, 三氟甲氧基试剂, 制备

Fluorine-containing organic molecules have broad applications in the fields of pharmaceuticals, agrochemicals, and material science. In the pharmaceutical industry, the incorporation of fluorine-containing methoxy groups can enhance the bioavailability and metabolic stability of drugs, while also modulating the stereochemistry and electronic structure of the molecules, thereby improving drug efficacy and selectivity. In the agricultural sector, fluorine-containing organic compounds exhibit significant insecticidal and fungicidal properties. In materials science, fluorine-containing methoxy compounds are widely used in the synthesis and modification of materials, such as batteries, coatings, and catalysts due to their excellent electrochemical performance and thermal stability. Consequently, the efficient introduction of fluorine-containing methoxy groups has become a focal point of research in organic chemistry. This review provides an overview of the preparation methods for monofluoromethoxy (OCH₂F), difluoromethoxy (OCF₂H), and trifluoromethoxy (OCF₃) reagents, as well as the development of trifluoromethoxy reagents.

Key words: monofluoromethoxy reagent, difluoromethoxy reagent, trifluoromethoxy reagent, preparation

引用此文

郑威, 刘凤雪, 赵红琼, 许颖, 陈宁, 刘颖杰. 单/二/三氟甲氧基化试剂的制备方法的研究进展[J]. 有机化学, 2024, 44(11): 3321-3334.

Wei Zheng, Fengxue Liu, Hongqiong Zhao, Ying Xu, Ning Chen, Yingjie Liu. Recent Progress on Methods for the Preparation of Mono/Di/Trifluoromethoxylation Reagents[J]. Chinese Journal of Organic Chemistry, 2024, 44(11): 3321-3334.

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图/表 29

图式1. O-[11C]甲基-l-酪氨酸和O-[18F]氟甲基-l-酪氨酸的合成

Scheme 1. Synthesis of O-[11C] methyl-l-tyrosine and O-[18F] fluoromethyl-l-tyrosine

图式2. 1-(氟甲氧基)-3-甲基-苯并三氮唑(FMBT)的合成

Scheme 2. Synthesis of 1-(fluoromethoxy)-3-methylbenzotriazole (FMBT)

图式3. N-(氟甲氧基)苯并三唑的合成

Scheme 3. Synthesis of N-(fluoromethoxy) benzotriazole

图式4. 2,6-二氯-(二氟甲氧基)苯胺的合成及应用

Scheme 4. Synthesis and application of 2,6-dichloro-(difluoro- methoxy) aniline

图式5. 二氟甲氧基试剂32的合成与应用

Scheme 5. Synthesis and application of difluoromethoxy reagent 32

图式6. TEMPO?催化的(杂)芳烃的C—H二氟/三氟甲氧基化反应

Scheme 6. TEMPO? catalyzed C—H difluoro/trifluoromethoxylation of (hetero) aromatic hydrocarbons

图式7. N-(二氟甲氧基)吡啶盐的合成及应用

Scheme 7. Synthesis and application of N-(difluoromethoxy) pyridine salt

图式8. 亲核三氟甲氧基化反应及可获得的三氟甲氧基阴离子源

Scheme 8. Nucleophilic trifluoromethoxylation reactions and obtainable trifluoro methoxide anion sources

图式9. 早期的三氟甲氧基试剂的制备

Scheme 9. Preparation of early trifluoromethoxy reagents

图式10. 自由基试剂N-三氟甲氧基邻苯二甲酰亚胺及其衍生物的制备

Scheme 10. Preparation of radical reagents N-(trifluorometh- oxy)phthalimide and its derivative

图式11. PhthOCF3的制备与应用

Scheme 11. Preparation and application of PhthOCF3

图式12. N-三氟甲氧基吡啶鎓盐试剂79的制备

Scheme 12. Preparation of N-trifluoromethoxy pyridinium salt reagent 79

图式13. 试剂81的制备与应用

Scheme 13. Preparation and application of reagent 81

图式14. 1-OCF3-苯并三唑试剂88的制备与应用

Scheme 14. Preparation and application of 1-OCF3 benzotriazole reagent 88

图式15. TAS OCF3的制备与应用

Scheme 15. Preparation and application of TAS OCF3

图式16. (Aryl-BIAN)AgOCF3的制备与应用

Scheme 16. Preparation and application of (Aryl-BIAN)- AgOCF3

图式17. 三氟甲基芳基磺酸盐试剂108的制备及应用

Scheme 17. Preparation and application of trifluoromethylaryl sulfonate reagent 108

图式18. (E)-O-三氟甲基苯甲醛肟的合成及应用

Scheme 18. Synthesis and application of (E)-O-trifluoromethyl benzaldehydeoxime

图式19. α-溴苄基三氟甲基醚(116)的制备与应用

Scheme 19. Preparation and application of α-bromobenzyl trifluoromethyl ether (116)

图式20. [Ag(bpy)(PPhtBu2)(OCF3)] (125)的制备与应用

Scheme 20. Preparation and application of [Ag(bpy)(PPhtBu2)(OCF3)] (125)

图式21. 三氟甲基三氟酸酯(130)的制备与应用

Scheme 21. Preparation and application of trifluoromethyl trifluoroate (130)

图式22. 三氟甲基苯甲酸酯(TFBz) (151)的制备与应用

Scheme 22. Preparation and application of trifluoromethyl benzoate(TFBz) (151)

图式23. AgOCF3的制备与应用

Scheme 23. Preparation and application of AgOCF3

图式24. PyOCF3的制备与应用

Scheme 24. Preparation and application of PyOCF3

图式25. 三氟甲基全氟丁烷磺酸(TFNf)的制备及应用

Scheme 25. Preparation and application of trifluoromethyl perfluorobutane sulfonic acid (TFNF)

图式26. 三氟甲氧基烯丙基碳酸酯的制备与应用

Scheme 26. Preparation and application of trifluoromethoxyallyl carbonate

图式27. 试剂N,N-二甲基吡咯烷鎓三氟甲氧基189的制备与应用

Scheme 27. Preparation and application of reagent N,N-dime- thylpyrrolium trifluoromethoxy 189

图式28. 试剂195的制备及应用

Scheme 28. Preparation and application of reagent 195

图式29. 试剂[Ag(PPhtBu2)(OCF3)]的制备及应用

Scheme 29. Preparation and application of reagent [Ag(PPh- tBu2)(OCF3)]

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