CN112159375A - Green preparation method of 2, 3-dihydrofuran compound - Google Patents
Green preparation method of 2, 3-dihydrofuran compound Download PDFInfo
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- CN112159375A CN112159375A CN202011006500.8A CN202011006500A CN112159375A CN 112159375 A CN112159375 A CN 112159375A CN 202011006500 A CN202011006500 A CN 202011006500A CN 112159375 A CN112159375 A CN 112159375A
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- 238000002360 preparation method Methods 0.000 title description 3
- -1 2, 3-dihydrofuran compound Chemical class 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 68
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 18
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical class C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 78
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 22
- 239000002994 raw material Substances 0.000 claims description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 11
- 238000004440 column chromatography Methods 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 11
- 238000001914 filtration Methods 0.000 claims description 11
- 239000012046 mixed solvent Substances 0.000 claims description 11
- 239000012074 organic phase Substances 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 claims description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 238000012805 post-processing Methods 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000000654 additive Substances 0.000 abstract description 5
- 230000000996 additive effect Effects 0.000 abstract description 5
- 239000007864 aqueous solution Substances 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- 230000002140 halogenating effect Effects 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 12
- 238000001035 drying Methods 0.000 description 10
- 239000012156 elution solvent Substances 0.000 description 10
- 238000012544 monitoring process Methods 0.000 description 9
- 230000035484 reaction time Effects 0.000 description 9
- 239000012295 chemical reaction liquid Substances 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 3
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical class CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/28—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及一种无任何添加剂体系下1，3‑二羰基化合物通过卤环化反应制备2，3‑二氢呋喃类化合物的绿色方法，反应在水溶液中室温下敞开在空气中进行。该方法通过向Schlenk反应瓶中加入1，3‑二羰基化合物、卤化试剂和溶剂，在室温下搅拌反应，得到目标产物。The invention relates to a green method for preparing 2,3-dihydrofuran compounds through halogen cyclization of 1,3-dicarbonyl compounds without any additive system, and the reaction is carried out in an aqueous solution in an open atmosphere at room temperature. In the method, a 1,3-dicarbonyl compound, a halogenated reagent and a solvent are added into a Schlenk reaction flask, and the reaction is stirred at room temperature to obtain the target product.
Description
Technical Field
The application belongs to the field of organic synthesis, and particularly relates to a green method for preparing 2, 3-dihydrofuran compounds from 1, 3-dicarbonyl compounds through halogen cyclization reaction without any additive system, wherein the reaction can be carried out in water solution at room temperature in the open air.
Background
Water, of low cost, safe, non-toxic and environmentally friendly nature, is certainly the most attractive chemical reaction medium in the green and sustainable chemical field. In addition, dimethyl sulfoxide (DMSO) is used as a general green solvent, and provides a wider space for the development of green organic reaction. On the other hand, the realization of organic reactions in air open at room temperature is one of the most desirable methods, since costs and energy consumption can be minimized. Therefore, organic transformations in water/DMSO mixed media open in air at room temperature are an attractive but challenging goal.
Electrophilic halocyclization of olefins has become an efficient strategy for the efficient preparation of cyclic compounds by introducing new halogen groups and generating new rings. In this context, there have been numerous investigations into the halocyclization of 1, 3-dicarbonyl compounds having allyl substitution. However, from the viewpoint of ecological friendliness and practicality, these achievements are still plagued by some disadvantages, such as the use of catalysts, the necessity of bases or oxidizing agents in the reaction, the need for higher reaction temperatures or toxic organic solvents. The present inventors have made intensive studies on the halocyclization reaction of a 1, 3-dicarbonyl compound, and in the present invention, we have proposed a halocyclization reaction method which can be carried out in an aqueous solution at room temperature in the open air. The method does not need to use any additive, and the reaction condition is mild and green.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for preparing 2, 3-dihydrofuran compounds from 1, 3-dicarbonyl compounds through halogen cyclization reaction, which is green, efficient and low in cost, does not need any additive, and can be used for preparing target products mildly with high yield.
The invention provides a halo cyclization reaction method, which takes a 1, 3-dicarbonyl compound and a halogenating reagent as raw materials and is prepared by the following steps:
adding a 1, 3-dicarbonyl compound shown in formula 1, a halogenating reagent shown in formula 2 and a solvent into a Schlenk reaction bottle, placing the reaction bottle at room temperature, stirring for reaction, monitoring the reaction progress by TLC or GC until the raw materials are completely reacted, and carrying out post-treatment to obtain a halogen cyclization product 2, 3-dihydrofuran (I).
The chemical reaction formula of the method for the halocyclization reaction of the 1, 3-dicarbonyl compound and the halogenating reagent provided by the invention can be expressed as (see formula I):
the post-processing operation is as follows: extracting the reaction solution after the reaction is finished with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove a solvent, and separating the residue by column chromatography, wherein the elution solvent is: ethyl acetate/n-hexane to give 2, 3-dihydrofuran (I).
In the compounds represented by formula 1 and formula I, R1Is selected from C5-C14Aryl radical, C1-C10An alkyl group;
R2is selected from C5-C14Aryl radical, C1-C10An alkyl group;
R3is selected from C5-C14Aryl radical, C1-C10Alkyl radical, C1-C6An ester group;
[X]selected from N-iodosuccinimide (NIS), trimethyl iodosilane (TMSI), iodine simple substance (I)2) Iodine chloride (ICl), N-bromosuccinimide (NBS);
wherein each R is1-R3The aryl and alkyl groups having the number of carbon atoms in the substituents are optionally substituted by a substituent selected from the group consisting of halogen, C1-C6Alkyl radical, C1-C6Alkoxy radical, C5-C14Aryl, halogen substituted C1-C6Alkyl, -NO2、-CN、C1-C6alkyl-C (═ O) -, C1-C6alkyl-OC (O ═ O) -.
Preferably, R1Is selected from C1Alkyl radical, C5-C14An aryl group;
R2is selected from C1Alkyl radical, C5-C14An aryl group;
R3is selected from C1Alkyl radical, C6Aryl radical, C1-C6An ester group.
In the reaction of the present invention, the solvent is selected from any one of a mixed solvent of dimethyl sulfoxide (DMSO)/water, Tetrahydrofuran (THF)/water, ethanol (EtOH)/water, and ethyl acetate (EtOAc)/water, and is preferably dimethyl sulfoxide (DMSO)/water.
In the reaction of the present invention, the amount of water in the mixed solvent of dimethyl sulfoxide (DMSO)/water is 1.5mL, and the amount of DMSO is 0.2-0.6mL, preferably 0.5 mL.
In the reaction of the present invention, the halogenating agent is used in an amount of 1.2 to 2 equivalents, preferably 1.2 equivalents.
The invention has the beneficial effects that: a process for preparing 2, 3-dihydrofurans from 1, 3-dicarbonyl compound and halogenating reagent by halocyclization reaction features that the reaction can be carried out in aqueous solution at room temp in air without any additive and a series of target products can be obtained in high yield. The method has the advantages of wide reaction substrate application range, greenness and high efficiency, and is particularly suitable for industrial production.
Detailed Description
The present invention will be described in further detail with reference to specific examples, but the present invention is not limited thereto.
The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and starting materials, if not otherwise specified, are commercially available and/or may be prepared according to known methods.
Examples 1-7 are experiments optimized for reaction conditions.
Example 1
A Schlenk flask was charged with a compound of formula 1a (55.6mg, 0.2mmol), a halogenating agent of formula 2a (54.0mg, 0.24mmol), DMSO/H2O (0.5mL/1.5mL), then stirring the reactor at room temperature for reaction, monitoring the reaction progress by TLC until the raw material disappears (the reaction time is 8 hours), after the reaction is finished, extracting the reaction liquid by using ethyl acetate, drying an organic phase by using anhydrous sodium sulfate, filtering and concentrating under reduced pressure to remove a solvent, and carrying out column chromatography separation on the residue (an elution solvent is ethyl acetate/n-hexane) to obtain a target product I-1 (95% yield);1H NMR(500MHz，CDCl3)：7.37-7.36(m，2H)，7.18-7.08(m，4H)，7.00-6.96(m，4H)，3.50-3.43(m，2H)，3.25-3.14(m，2H)，1.67(s，3H)；13C NMR(125MHz，CDCl3)：193.4，164.4，138.9，131.2，130.1，130.0，129.3，129.0，127.7，111.9，85.2，44.2，26.2，15.0。
example 2
The amount of the halogenating agent NIS used was 2.0eq (90.0mg), and the other conditions were the same as in example 1, whereby the yield of the objective product I-1 was 96%.
Example 3
The DMSO content was 0.2mL, and the yield of the target product I-1 was 20% under the same conditions as in example 1.
Example 4
The DMSO content was 0.6mL, and the yield of the target product I-1 was 95% under the same conditions as in example 1.
Example 5
The DMSO/water mixed solvent was replaced by a THF/water mixed solvent under the same conditions as in example 1 to obtain the desired product I-1 in a yield of 61%.
Example 6
The DMSO/water mixed solvent was replaced by EtOH/water mixed solvent, and the other conditions were the same as in example 1, to obtain the desired product I-1 with a yield of 88%.
Example 7
The DMSO/water mixed solvent was replaced by EtOAc/water mixed solvent under the same conditions as in example 1 to obtain the desired product I-1 in a yield of 91%.
As can be seen from the above examples 1-7, the optimum reaction conditions were those of example 1, i.e., the amount of halogenating agent NIS used was 1.2eq (54.0mg), DMSO/H2O (0.5mL/1.5mL) was used as a mixed solvent, and then the reactor was reacted at room temperature. On the basis of obtaining the optimal reaction condition, the inventor further selects 1, 3-dicarbonyl compounds with different substituents and halogenating reagents as raw materials under the optimal reaction condition to develop a method for preparing 2, 3-dihydrofuran compounds by green halocyclization reaction.
Example 8
A Schlenk flask was charged with a compound of formula 1a (55.6mg, 0.2mmol), a halogenating agent of formula 2b (48.0mg, 0.24mmol), DMSO/H2O (0.5mL/1.5mL), then stirring the reactor at room temperature for reaction, monitoring the reaction progress by TLC until the raw material disappears (the reaction time is 8 hours), after the reaction is finished, extracting the reaction liquid by ethyl acetate, drying the organic phase by anhydrous sodium sulfate, filtering and decompressing and concentrating to remove the solvent, and separating the residue by column chromatography (the elution solvent is ethyl acetate/n-hexane) to obtain the target product I-1 (13% yield).
Example 9
A Schlenk flask was charged with a compound of formula 1a (55.6mg, 0.2mmol), a halogenating agent of formula 2c (61.0mg, 0.24mmol), DMSO/H2O (0.5mL/1.5mL), then stirring the reactor at room temperature for reaction, monitoring the reaction progress by TLC until the raw material disappears (the reaction time is 8 hours), after the reaction is completed, extracting the reaction liquid with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, filtering and concentrating under reduced pressure to remove the solvent, and separating the residue by column chromatography (the elution solvent is ethyl acetate/n-hexane) to obtain the target product I-1 (89% yield).
Example 10
To a Schlenk flask was added a compound of formula 1a (55.6mg, 0.2mmol), a halogenating agent of formula 2d (38.9mg, 0.24mmol), DMSO/H2O (0.5mL/1.5mL), stirring the reactor at room temperature, monitoring the reaction progress by TLC until the raw material disappears (reaction time is 8 hours), extracting the reaction solution with ethyl acetate after the reaction is completed, drying the organic phase with anhydrous sodium sulfate, filtering and concentrating under reduced pressure to remove the solvent, and separating the residue by column chromatography (elution solvent: ethyl acetate/n-hexane)Alkane) to obtain the target product I-1 (32% yield).
Example 11
To a Schlenk flask was added a compound of formula 1a (55.6mg, 0.2mmol), a halogenating agent of formula 2e (42.7mg, 0.24mmol), DMSO/H2O (0.5mL/1.5mL), then stirring the reactor at room temperature for reaction, monitoring the reaction progress by TLC until the raw material disappears (the reaction time is 8 hours), after the reaction is finished, extracting the reaction liquid by ethyl acetate, drying an organic phase by anhydrous sodium sulfate, filtering and decompressing and concentrating to remove a solvent, and separating the residue by column chromatography (an elution solvent is ethyl acetate/n-hexane) to obtain a target product I-2 (72% yield);1H NMR(500MHz，CDCl3)：7.44-7.42(m，2H)，7.21-7.16(m，4H)，7.09-7.04(m，4H)，3.70-3.61(m，2H)，3.38(d，J＝19.5Hz，1H)，3.20(d，J＝19.0Hz，1H)，1.71(s，3H)；13C NMR(125MHz，CDCl3)：193.5，164.5，138.9，131.2，130.2，130.1，129.9，129.3，128.9，127.7，111.8，85.6，43.1，39.7，25.4。
example 12
A Schlenk flask was charged with a compound of formula 1b (76.4mg, 0.2mmol), a halogenating agent of formula 2a (54.0mg, 0.24mmol), DMSO/H2O (0.5mL/1.5mL), then stirring the reactor at room temperature for reaction, monitoring the reaction progress by TLC until the raw material disappears (the reaction time is 8 hours), after the reaction is finished, extracting the reaction liquid by ethyl acetate, drying an organic phase by anhydrous sodium sulfate, filtering and decompressing and concentrating to remove a solvent, and separating the residue by column chromatography (an elution solvent is ethyl acetate/n-hexane) to obtain a target product I-3 (96% yield); yellow oil (0.0975g, 96% yield);1H NMR(500MHz，CDCl3)：8.02-8.01(m，4H)，6.94-6.89(m，4H)，3.86(d，J＝6.0Hz，2H)，3.84(s，6H)，3.77(s，3H)，3.74(d，J＝7.0Hz，1H)，3.08(d，J＝6.5Hz，1H)；13C NMR(125MHz，CDCl3)：194.1，173.8，167.5，163.9，163.8，136.5，131.4，131.2，130.0，129.7，129.1，114.0，85.7，55.5，54.7，51.9，32.6，14.1。
example 13
A Schlenk flask was charged with a compound of formula 1c (43.2mg, 0.2mmol), a halogenating agent of formula 2a (54.0mg, 0.24mmol), DMSO/H2O (0.5mL/1.5mL), then stirring the reactor at room temperature for reaction, monitoring the reaction progress by TLC until the raw material disappears (the reaction time is 8 hours), after the reaction is completed, extracting the reaction solution with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, filtering and concentrating under reduced pressure to remove the solvent, and separating the residue by column chromatography (the elution solvent is ethyl acetate/n-hexane) to obtain the target products I-4 and I-4' (I-4: I-4 ═ 2: 1, 78% yield);1H NMR(500MHz，CDCl3)：7.60-7.57(m，2H)，7.50-7.44(m，3H)，3.49-3.41(m，2H)，3.21-3.13(m，1H)，3.04-2.95(m，1H)，1.98(s，1H)，1.85(s，2H)，1.70(s，1H)，1.64(s，2H)；13C NMR(125MHz，CDCl3)：194.8，193.2，167.8，165.5，140.6，131.2，130.8，130.7，129.2，128.4，128.3，127.8，114.6，112.3，85.8，85.7，42.8，42.6，28.8，26.2，26.1，15.7，15.0。
example 14
To a Schlenk flask was added a compound of formula 1d (58.6mg, 0.2mmol), a halogenating agent of formula 2a (54.0mg, 0.24mmol), DMSO/H2O (0.5mL/1.5mL), then the reactor was stirred at room temperature and the progress of the reaction was monitored by TLCWhen the raw materials disappear (the reaction time is 8 hours), after the reaction is finished, extracting the reaction liquid by ethyl acetate, drying an organic phase by anhydrous sodium sulfate, filtering and concentrating under reduced pressure to remove a solvent, and separating the residue by column chromatography (the elution solvent is ethyl acetate/n-hexane) to obtain target products I-5 and I-5 '(I-5: I-5' ═ 4: 1, 73% yield);1H NMR(500MHz，CDCl3)：8.08(t，J＝7.5Hz，0.8H)，7.67-7.66(m，2H)，7.52-7.47(m，3H)，7.23(d，J＝4.0Hz，3H)，7.04-7.01(m，1.2H)，3.53-3.47(m，2H)，3.25(d，J＝15.5Hz，1H)，3.11(d，J＝15.5Hz，1H)，1.76(s，0.6H)，1.70(s，2.4H)；13C NMR(125MHz，CDCl3)：192.4，162.8，158.5，138.0，135.3，134.2(2)，131.1，130.9，129.9，129.7(2)，129.1，128.9，128.8(2)，128.6，127.6，123.8，119.2，106.8，84.7，43.3，26.1，15.1。
example 15
A Sehlenk flask was charged with a compound of formula 1e (68.0mg, 0.2mmol), a halogenating agent of formula 2a (54.0mg, 0.24mmol), DMSO/H2O (0.5mL/1.5mL), then stirring the reactor at room temperature for reaction, monitoring the reaction progress by TLC until the raw material disappears (the reaction time is 8 hours), after the reaction is finished, extracting the reaction liquid by ethyl acetate, drying an organic phase by anhydrous sodium sulfate, filtering and decompressing and concentrating to remove a solvent, and separating the residue by column chromatography (an elution solvent is ethyl acetate/n-hexane) to obtain a target product I-6 (85% yield);1H NMR(500MHz，CDCl3)：7.51(d，J＝7.5Hz，2H)，7.46(d，J＝7.0Hz，2H)，7.42(t，J＝8.0Hz，2H)，7.35(t，J＝8.0Hz，3H)，7.22(t，J＝7.5Hz，2H)，7.13-7.07(m，4H)，3.80-3.77(m，2H)，3.75(d，J＝3.0Hz，1H)，3.71(d，J＝15.5Hz，1H)；13C NMR(125MHz，CDCl3)：193.0，164.1，142.5，138.8，131.3，130.2，129.8，129.4，129.0，128.8，128.2，127.7(2)，125.0，112.2，87.5，45.4，16.9。
example 16 reaction mechanism control experiment
To further verify the reaction mechanism of this reaction, the following two sets of control experiments were performed. By adding 2.0 equivalents of tetramethylpiperidine nitroxide (TEMPO) or 2, 6-di-tert-butyl-4-methylphenol (BHT) as a radical scavenger to the reaction of example 1, the desired product was still obtained in 77% and 88% yields, respectively, eliminating the possibility of the reaction going through a radical reaction process.
It follows that the possible reaction mechanism of the present invention can be deduced as shown in the following formula:
the embodiments described above are only preferred embodiments of the invention and are not exhaustive of the possible implementations of the invention. Any obvious modifications to the above would be obvious to those of ordinary skill in the art, but would not bring the invention so modified beyond the spirit and scope of the present invention.
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