CN114671834A - Synthesis method of gem-dibromo alkenyl dihydrofuran compound - Google Patents

Synthesis method of gem-dibromo alkenyl dihydrofuran compound Download PDF

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CN114671834A
CN114671834A CN202210201313.8A CN202210201313A CN114671834A CN 114671834 A CN114671834 A CN 114671834A CN 202210201313 A CN202210201313 A CN 202210201313A CN 114671834 A CN114671834 A CN 114671834A
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dibromoalkenyl
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dihydrofuran
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伍婉卿
陈扬
马瑞泽
方松佳
江焕峰
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South China University of Technology SCUT
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    • 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
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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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    • 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
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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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Abstract

The invention discloses a synthetic method of a gem-dibromo alkenyl dihydrofuran compound. The synthesis method of the gem-dibromo alkenyl dihydrofuran compound comprises the following steps: mixing the 5-triisopropyl silyl enealkynone compound and the alcohol compound for reaction to obtain the gem-dibromo alkenyl dihydrofuran compound. The invention constructs a series of gem-dibromo alkenyl dihydrofuran compounds with unique performance by utilizing 5-triisopropyl silyl enealkynone compounds and monohydric alcohol to carry out 5-exo-dig cyclization reaction, and has the advantages of simple and easily obtained raw materials, safe operation, mild reaction conditions, wide substrate applicability and the like.

Description

Synthesis method of gem-dibromo alkenyl dihydrofuran compound
Technical Field
The invention relates to the technical field of furan compound synthesis, in particular to a synthetic method of a gem-dibromo alkenyl dihydrofuran compound.
Background
The furan compound is a common oxygen-containing five-membered heterocyclic compound, can show special chemical properties and biological activity, and is widely applied to the fields of novel medicines, material science, spices, chemical auxiliaries and the like. Furthermore, furan rings have multiple reactive sites and are often used as building blocks for the synthesis of complex heterocyclic compounds. Therefore, the synthesis and modification of such heterocyclic compounds is of great importance in the field of synthetic chemistry.
Alkynyl is an important structural motif in organic chemistry and is an excellent reaction precursor for participating in various types of transformations. The enynone compound is a unique functionalized alkyne, and has a larger conjugated system and larger charge deviation compared with the common alkyne, so that the enynone compound has richer reaction sites and stronger reactivity. At present, the construction of furan compounds by using eneynone compounds as raw materials has become an important component in the synthetic chemistry of furan compounds. Generally, alkenyl, alkynyl and carbonyl carbon in the alkenone compound all have certain electrophilic activity, and all the three can react with a nucleophilic reagent under certain conditions. In the methods reported so far for constructing furan skeleton with enynone compounds, most of the reactions are realized by forming metal carbene, and the metal carbene intermediate formed in the reaction can accept attack of nucleophilic reagent in the system, or accept insertion of silicon hydrogen bond, alkyne and isonitrile, or realize construction of furan skeleton by subsequent tandem cyclization (for example, J.Huang, F.Li and L.Cui, chem.Commun.,2020,56, 4555; M.Y.Huang, J.M.Yang and Y.T.Zhao, ACS.Cat., 2019,9, 5353; L.Chen, K.Waand Y.Shao, org.Lett.,2019,21, 3804; H.Zhang, T.Cao and H.Luo, org.Front., Chent., 2019,6, 1118; H.Peng.Wan.W.14156, Zhang, 26, 2020). However, the furan skeleton synthesized by these methods is often of simpler structure, and the research on synthesis of some furan compounds with higher degree of functionalization (especially furan compounds containing multiple bromine atoms) is still very lacking. It is well known that carbon-bromine bonds are easily converted into other functional groups by easily operable cross-coupling reactions, and the introduction of carbon-bromine bonds is of great significance for the post-modification of furan skeletons.
Therefore, the development of a method for synthesizing the gem-dibromoalkenyl dihydrofuran compound different from the metal carbene catalysis is of great significance.
Disclosure of Invention
The invention aims to provide a synthetic method of a geminal dibromoalkenyl dihydrofuran compound.
The technical scheme adopted by the invention is as follows:
the synthesis method of the gem-dibromo alkenyl dihydrofuran compound comprises the following steps: mixing the 5-triisopropyl silyl enealkynone compound and monohydric alcohol for reaction to obtain the gem-dibromo alkenyl dihydrofuran compound.
Preferably, the synthesis method of the geminal dibromoalkenyl dihydrofuran compound comprises the following steps: dispersing a palladium catalyst, a ligand, N-bromosuccinimide (NBS) and an additive in an organic solvent, adding a 5-triisopropyl silyl enealkynone compound and monohydric alcohol, and reacting in a protective atmosphere to obtain the geminal dibromoalkenyl dihydrofuran compound.
Preferably, the structural formula of the 5-triisopropylsilylenynone compound is shown in the specification
Figure BDA0003527550110000021
In the formula, R1One selected from methyl, propyl, cyclopropyl and cyclobutyl, R2Is selected from one of acetyl, ethoxyacyl, propoxyl and butoxyacyl. Note: TIPS stands for triisopropylsilyl
Figure BDA0003527550110000022
Preferably, the monohydric alcohol is selected from one of methanol, ethanol, isoamyl alcohol, benzyl alcohol, 4-chlorobenzyl alcohol, 4-methylbenzyl alcohol, 6-chlorohexanol, 2-methoxyacyl ethanol and 2-methoxyethanol.
Preferably, the molar ratio of the 5-triisopropylsilylenynone compound to the monohydric alcohol is 1: 3-6.
Preferably, the reaction is carried out at normal temperature, and the reaction time is 6-8 h.
Preferably, the palladium catalyst is at least one selected from palladium dichloride, bis-triphenylphosphine palladium dichloride and 1, 3-bis-diphenylphosphinopropane palladium dichloride.
Preferably, the molar ratio of the 5-triisopropylsilylenynone compound to the palladium catalyst is 1: 0.05-0.20.
Preferably, the ligand is at least one selected from the group consisting of 1, 10-phenanthroline, 2-methyl-1, 10-phenanthroline, 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline.
Preferably, the molar ratio of the 5-triisopropylsilylenynone compound to the ligand is 1: 0.05-0.20.
Preferably, the molar ratio of the 5-triisopropylsilylenynone compound to the N-bromosuccinimide is 1: 1.5-2.0.
Preferably, the additive is a mixture of silver trifluoroacetate, potassium fluoride and a crown ether.
Preferably, the crown ether is 18-crown-6.
Preferably, the molar ratio of the 5-triisopropylsilylenynone compound to the silver trifluoroacetate is 1: 0.05-0.50.
Preferably, the molar ratio of the 5-triisopropylsilylenynone compound to the potassium fluoride is 1: 1.0-1.5.
Preferably, the molar ratio of the 5-triisopropylsilylenynone compound to the crown ether is 1: 1.0-1.5.
Preferably, the organic solvent is at least one selected from acetonitrile and tetrahydrofuran.
Preferably, the protective atmosphere is a nitrogen atmosphere.
Preferably, after the reaction is finished, a product purification operation is further performed, and the specific operation is as follows: extracting the reaction liquid with ethyl acetate, combining organic phases, drying with anhydrous magnesium sulfate, filtering, distilling the filtrate under reduced pressure, and purifying by column chromatography.
Preferably, the eluent adopted by the column chromatography purification is composed of petroleum ether and ethyl acetate according to the volume ratio of 10-50: 1.
Further preferably, the eluent adopted by the column chromatography purification is composed of petroleum ether and ethyl acetate according to the volume ratio of 20-30: 1.
The reaction formula of the 5-triisopropylsilylenynone compound and the monohydric alcohol in the invention is as follows:
Figure BDA0003527550110000031
In the formula, R1One selected from methyl, propyl, cyclopropyl and cyclobutyl, R2One selected from acetyl, ethoxyacyl, propoxoyl and butoxyacyl, R3Is selected from one of methyl, ethyl, isoamyl, benzyl, 4-chlorobenzyl, 4-methylbenzyl, 6-chlorohexyl, 2-methoxylethyl and 2-methoxyethyl.
The invention has the beneficial effects that: the invention constructs a series of gem-dibromo alkenyl dihydrofuran compounds with unique performance by utilizing 5-triisopropyl silyl enealkynone compounds and monohydric alcohol to carry out 5-exo-dig cyclization reaction, and has the advantages of simple and easily obtained raw materials, safe operation, mild reaction conditions, wide substrate applicability and the like.
Specifically, the method comprises the following steps:
1) the basic raw material 5-triisopropylsilyl enynone compound adopted in the invention can be synthesized by cheap 1, 3-diketone compounds and 3- (triisopropylsilyl) propynal, and the raw material is simple and easy to obtain and has low production cost;
2) the method for synthesizing the gem-dibromo alkenyl dihydrofuran compound has the advantages of simple and easily obtained raw materials, safe operation, mild reaction conditions, wide substrate applicability, good tolerance to functional groups, low cost and the like, and is suitable for industrial production and further derivatization.
Drawings
FIG. 1 shows the NMR spectrum of the gem-dibromoalkenyl dihydrofuran compound of example 1.
FIG. 2 shows the NMR carbon spectrum of the geminal dibromoalkenyl dihydrofuran compound of example 1.
FIG. 3 shows the NMR spectrum of the dibromoalkenyldihydrofuran compound of example 2.
FIG. 4 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 2.
FIG. 5 shows the NMR spectra of the gem-dibromoalkenyl dihydrofurans of example 3.
FIG. 6 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 3.
FIG. 7 shows the NMR spectra of the gem-dibromoalkenyl dihydrofurans of example 4.
FIG. 8 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 4.
FIG. 9 shows the NMR spectra of the gem-dibromoalkenyl dihydrofurans of example 5.
FIG. 10 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 5.
FIG. 11 shows the NMR spectra of the gem-dibromoalkenyl dihydrofurans of example 6.
FIG. 12 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 6.
FIG. 13 shows the NMR spectrum of the gem-dibromoalkenyl dihydrofurans of example 7.
FIG. 14 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 7.
FIG. 15 shows the NMR spectrum of the gem-dibromoalkenyl dihydrofurans of example 8.
FIG. 16 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 8.
FIG. 17 shows the NMR spectrum of the gem-dibromoalkenyl dihydrofurans of example 9.
FIG. 18 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 9.
FIG. 19 shows the NMR spectrum of the gem-dibromoalkenyl dihydrofurans of example 10.
FIG. 20 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 10.
FIG. 21 shows the NMR spectrum of the gem-dibromoalkenyl dihydrofurans of example 11.
FIG. 22 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 11.
FIG. 23 shows the NMR spectrum of the gem-dibromoalkenyl dihydrofurans of example 12.
FIG. 24 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 12.
FIG. 25 shows the NMR spectrum of the gem-dibromoalkenyl dihydrofurans of example 13.
FIG. 26 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 13.
FIG. 27 shows the NMR spectrum of the gem-dibromoalkenyl dihydrofurans of example 14.
FIG. 28 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 14.
FIG. 29 shows the NMR spectrum of the gem-dibromoalkenyl dihydrofurans of example 15.
FIG. 30 shows the NMR spectrum of the geminal dibromoalkenyl dihydrofurans of example 15.
Detailed Description
The invention will be further explained and illustrated with reference to specific examples.
Example 1:
the synthesis method of the gem-dibromo alkenyl dihydrofuran compound comprises the following steps:
adding 0.02mmol of palladium dichloride, 0.02mmol of 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline, 0.2mmol of N-bromosuccinimide, 0.05mmol of silver trifluoroacetate, 0.12mmol of potassium fluoride and 0.12mmol of 18-crown ether-6 into 1mL of dry acetonitrile, stirring for dispersion, and adding 0.1mmol of 1-methyl-2-acetyl (5-triisopropylsilyl) eneynone
Figure BDA0003527550110000051
) And 0.5mmol of methanol, stirring at normal temperature in nitrogen atmosphere at 700rpm for 6 hr, stopping stirring, and adding 5And then extracting the reaction liquid with ethyl acetate for 3 times by using mL of water, combining organic phases, drying the organic phases by using 0.5g of anhydrous magnesium sulfate, filtering, distilling the filtrate under reduced pressure, and then carrying out column chromatography purification, wherein eluent adopted by the column chromatography purification consists of petroleum ether and ethyl acetate according to the volume ratio of 20:1, so that the dibromoalkenyl dihydrofuran compound (yield: 74%) is obtained.
The nmr hydrogen spectrum of the synthesized gem-dibromoalkenyl dihydrofuran compound is shown in fig. 1, the nmr carbon spectrum is shown in fig. 2, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CD3CN)：δ7.37(s,1H),3.06(s,3H),2.40(s,3H),1.63(s,3H)；
13C NMR(100MHz,CD3CN)：δ193.4,155.3,143.7,132.7,116.2,69.9,27.3,23.7；
IR(KBr)νmax：3391,2927,1676,1234,789cm-1；
HRMS(ESI)Calcd for C9H10Br2NaO3[M+Na]+：346.8894,Found 346.8894；
in conclusion, the structural formula of the gem-dibromoalkenyl dihydrofuran compound synthesized in the embodiment is as follows:
Figure BDA0003527550110000052
example 2:
a gem-dibromoalkenyl dihydrofuran compound which is the same as the example 1 except that the raw material (monohydric alcohol) is replaced by methanol to ethanol in the synthesis process.
The yield of the geminal dibromoalkenyldihydrofurans in this example was 83%.
The nmr hydrogen spectrum and nmr carbon spectrum of the synthesized gem-dibromoalkenyl dihydrofurans compound in this example are shown in fig. 3 and fig. 4 respectively, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.19(s,1H),3.53-3.38(m,1H),3.32-3.12(m,1H),2.44(s,3H),1.77(s,3H),1.21(t,J＝7.0Hz,3H)；
13C NMR(100MHz,CDCl3)：δ192.2,154.3,144.1,131.6,115.5,71.0,59.1,27.5,24.3,14.8；
IR(KBr)νmax：3595,3387,3114,1702,982,561cm-1；
HRMS(ESI)Calcd for C10H12Br2NaO3[M+Na]+：360.9045,Found 360.9043；
In conclusion, the structural formula of the gem-dibromoalkenyl dihydrofuran compound synthesized in the embodiment is as follows:
Figure BDA0003527550110000061
example 3:
a geminal dibromoalkenyl dihydrofuran compound which is the same as the compound in the embodiment 1 except that the raw material (monohydric alcohol) is replaced by methanol into isoamyl alcohol in the synthesis process.
The yield of the gem-dibromoalkenyldihydrofurans in this example was 85%.
The nmr hydrogen spectrum of the synthesized gem-dibromoalkenyl dihydrofuran compound in this example is shown in fig. 5, the nmr carbon spectrum is shown in fig. 6, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.26(s,1H),4.16-3.90(m,2H),3.50-3.40(m,1H),3.33-3.14(m,1H),1.99(m,1H),1.75(s,3H),1.17(t,J＝7.0Hz,3H),0.96(d,J＝6.7Hz,6H)；
13C NMR(100MHz,CDCl3)：δ161.7,154.6,138.9,132.8,115.4,71.4,70.6,59.4,27.8,24.7,19.1,15.1；
IR(KBr)νmax：3447,1672,1413,1237,927,628cm-1；
HRMS(ESI)Calcd for C13H18Br2NaO3[M+Na]+：402.9515,Found 402.9517；
in conclusion, the structural formula of the gem-dibromoalkenyl dihydrofurans synthesized in the example is as follows:
Figure BDA0003527550110000062
example 4:
a gem-dibromoalkenyl dihydrofuran compound which is the same as the example 1 except that the reaction raw material (monohydric alcohol) is replaced by benzyl alcohol, the volume ratio of petroleum ether and ethyl acetate in eluent is adjusted to 30:1 from 20:1 in the synthesis process.
The yield of the geminal dibromoalkenyldihydrofurans in this example was 84%.
The nmr hydrogen spectrum and nmr carbon spectrum of the synthesized gem-dibromoalkenyl dihydrofurans compound in this example are shown in fig. 7 and 8 respectively, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.28-7.26(m,5H),7.17(s,1H),4.46(d,J＝8.8Hz,1H),4.26(d,J＝9.2Hz,1H),)2.33(s,3H),1.82(s,3H)；
13C NMR(100MHz,CDCl3)：δ154.4,144.2,136.8,131.7,128.1,127.8,127.5,115.5,71.5,65.8,29.4,27.5,24.4；
IR(KBr)νmax：2927,2044,1691,1390,1162,624cm-1；
HRMS(ESI)Calcd for C15H14Br2NaO3[M+Na]+：422.9189,Found 422.9207；
In conclusion, the structural formula of the gem-dibromoalkenyl dihydrofurans synthesized in the example is as follows:
Figure BDA0003527550110000071
example 5:
the same procedure used in example 1 was repeated except that the starting material (monohydric alcohol) was replaced with 4-chlorobenzyl alcohol during the synthesis.
The yield of the geminal dibromoalkenyldihydrofurans in this example was 89%.
The nmr hydrogen spectrum and nmr carbon spectrum of the synthesized gem-dibromoalkenyl dihydrofurans compound in this example are shown in fig. 9 and 10 respectively, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.34-7.24(m,4H),7.22(s,1H),4.43(d,J＝11.2Hz,1H),4.24(d,J＝11.2Hz,1H),2.40(s,3H),1.83(s,3H)；
13C NMR(100MHz,CDCl3)：δ192.5,154.5,144.1,135.6,133.6,132.1,129.3,128.5,115.7,72.1,65.2,27.8,24.6；
IR(KBr)νmax：3407,3094,1682,1575,1164,638cm-1；
HRMS(ESI)Calcd for C15H13Br2ClNaO3[M+Na]+：456.9089,Found 456.8816；
in conclusion, the structural formula of the gem-dibromoalkenyl dihydrofurans synthesized in the example is as follows:
Figure BDA0003527550110000072
example 6:
the same procedure used in example 1 was repeated except that the starting material (monohydric alcohol) was replaced with 4-methylbenzyl alcohol during the synthesis.
The yield of the geminal dibromoalkenyldihydrofurans in this example was 92%.
The nmr hydrogen spectrum and nmr carbon spectrum of the synthesized gem-dibromoalkenyl dihydrofurans compound in this example are shown in fig. 11 and 12 respectively, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.29-7.10(m,5H),4.46(d,J＝10.8Hz,1H),4.25(d,J＝10.8Hz,1H),2.32(s,6H),1.80(s,3H)；
13C NMR(100MHz,CDCl3)：δ192.4,154.8,144.6,137.4,134.8,131.8,130.4,128.3,125.8,115.7,71.6,64.5,27.8,24.6,19.0；
IR(KBr)νmax：3597,1684,1560,1164,962,639cm-1；
HRMS(ESI)Calcd for C16H16Br2NaO3[M+Na]+：436.8889,Found 436.9365；
In conclusion, the structural formula of the gem-dibromoalkenyl dihydrofurans synthesized in the example is as follows:
Figure BDA0003527550110000081
example 7:
a gem-dibromoalkenyldihydrofuran compound which is the same as the compound in the embodiment 1 except that the reaction raw material (monohydric alcohol) is replaced by 6-chlorohexanol instead of methanol in the synthesis process.
The yield of the geminal dibromoalkenyldihydrofurans in this example was 86%.
The nmr hydrogen spectrum and nmr carbon spectrum of the synthesized gem-dibromoalkenyl dihydrofurans compound in this example are shown in fig. 13 and 14 respectively, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.16(s,1H),3.35(q,J＝6.8Hz,1H),3.13(q,J＝7.0Hz,1H),2.41(s,3H),1.74(s,2H),1.59(s,2H),1.32-1.25(m,6H),0.88(s,J＝6.5Hz,3H)；
13C NMR(100MHz,CDCl3)：δ192.5,154.7,144.6,131.8,115.9,71.2,63.9,31.5,29.5,27.8,25.6,24.6,22.5,14.0；
IR(KBr)νmax：3413,2926,1679,1399,1239,693,627cm-1；
HRMS(ESI)Calcd for C14H19Br2ClNaO3[M+Na]+：450.8879,Found 450.9291；
in conclusion, the structural formula of the gem-dibromoalkenyl dihydrofurans synthesized in the example is as follows:
Figure BDA0003527550110000082
example 8:
a gem-dibromoalkenyl dihydrofuran compound is completely the same as the example 1 except that the reaction raw material (monohydric alcohol) is replaced by 2-methoxy acyl ethanol from methanol, and the volume ratio of petroleum ether to ethyl acetate in eluent is adjusted to 30:1 from 20:1 in the synthesis process.
The yield of the geminal dibromoalkenyldihydrofurans in this example was 81%.
The nmr hydrogen spectrum and nmr carbon spectrum of the synthesized gem-dibromoalkenyl dihydrofurans compound in this example are shown in fig. 15 and 16, respectively, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.18(s,1H),3.67(s,3H),3.61(t,J＝7.6Hz,1H),3.49-3.41(m,1H),2.58(q,J＝7.2,6.0Hz,2H),2.42(s,3H),1.73(s,3H)；
13C NMR(100MHz,CDCl3)：δ192.45,171.6,154.5,143.9,132.0,115.6,71.8,59.2,51.8,34.5,27.9,24.5；
IR(KBr)νmax：3405,2926,1680,1339,1236,625cm-1；
HRMS(ESI)Calcd for C12H14Br2NaO5[M+Na]+：418.9089,Found 418.9109；
In conclusion, the structural formula of the gem-dibromoalkenyl dihydrofuran compound synthesized in the embodiment is as follows:
Figure BDA0003527550110000091
example 9:
a gem-dibromoalkenyl dihydrofuran compound is the same as in example 1 except that methanol is replaced by 2-methoxyethanol as a reaction raw material (monohydric alcohol), and the volume ratio of petroleum ether to ethyl acetate in eluent is adjusted to 10:1 from 20:1 in the synthesis process.
The yield of the gem-dibromoalkenyldihydrofurans in this example was 69%.
The nmr hydrogen spectrum of the synthesized gem-dibromoalkenyl dihydrofuran compound is shown in fig. 17, the nmr carbon spectrum is shown in fig. 18, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.17(s,1H),3.50(d,J＝7.1Hz,3H),3.33(m,4H),2.41(s,3H),1.76(s,3H)；
13C NMR(100MHz,CDCl3)：δ192.5,154.7,144.5,132.0,115.8,71.6,71.1,62.9,58.9,27.9,24.5；
IR(KBr)νmax：3400,2925,2855,1678,1236,785,626cm-1；
HRMS(ESI)Calcd for C11H14Br2NaO4[M+Na]+：390.9154,Found 390.9156；
in conclusion, the structural formula of the gem-dibromoalkenyl dihydrofuran compound synthesized in the embodiment is as follows:
Figure BDA0003527550110000101
example 10:
the synthesis method of the gem-dibromo alkenyl dihydrofuran compound comprises the following steps:
0.02mmol of palladium dichloride, 0.02mmol of 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline, 0.2mmol of N-bromosuccinimide, 0.05mmol of silver trifluoroacetate and 0.12mAdding 0.12mmol of 18-crown-6 and potassium fluoride into 1mL of dry acetonitrile, stirring for dispersion, adding 0.1mmol of 1-propyl-2-ethoxyacyl (5-triisopropylsilyl) enynone
Figure BDA0003527550110000102
And 0.5mmol of ethanol, stirring for 6 hours at normal temperature in a nitrogen atmosphere, stopping stirring, adding 5mL of water, extracting the reaction liquid for 3 times by using ethyl acetate, combining organic phases, drying by using 0.5g of anhydrous magnesium sulfate, filtering, distilling the filtrate under reduced pressure, and purifying by column chromatography, wherein an eluent used for the purification by the column chromatography consists of petroleum ether and ethyl acetate according to the volume ratio of 50:1, so that the gem-dibromoalkenyl dihydrofuran compound (yield: 74%) is obtained.
The nmr hydrogen spectrum and nmr carbon spectrum of the synthesized gem-dibromoalkenyl dihydrofurans compound in this example are shown in fig. 19 and 20 respectively, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.29(s,1H),4.28(q,J＝7.1Hz,2H),3.50-3.40(m,1H),3.32-3.23(m,1H),2.07(m,2H),1.33(t,J＝7.2Hz,3H),1.18(t,J＝7.0Hz,3H),0.91(t,J＝7.4Hz,3H)；
13C NMR(100MHz,CDCl3)：δ161.3,154.7,137.5,132.9,117.3,67.0,61.0,58.7,39.0,16.1,14.8,13.8,13.6；
IR(KBr)νmax：2976,1718,1330,1241,1099,903,766cm-1；
HRMS(ESI)Calcd for C13H18Br2NaO4[M+Na]+：404.9375,Found 404.9375；
in conclusion, the structural formula of the gem-dibromoalkenyl dihydrofuran compound synthesized in the embodiment is as follows:
Figure BDA0003527550110000103
example 11:
gem-dibromoThe alkenyl dihydrofuran compound is synthesized by replacing the reaction raw material (5-triisopropylsilyl-alkenylalkynone compound) with 1-propyl-2-ethoxyacyl (5-triisopropylsilyl) alkenylalkynone
Figure BDA0003527550110000111
The same procedure as in example 10 was repeated except that the volume ratio of petroleum ether to ethyl acetate in the eluate was adjusted from 50:1 to 20: 1.
The yield of the geminal dibromoalkenyldihydrofurans in this example was 63%.
The nmr hydrogen spectrum and nmr carbon spectrum of the synthesized gem-dibromoalkenyl dihydrofurans compound in this example are shown in fig. 21 and 22 respectively, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.22(s,1H),4.30(q,J＝7.2Hz,2H),3.58-3.49(m,1H),3.42-3.33(m,1H),1.58(m,1H),1.34(t,J＝7.2Hz,3H),1.20(t,J＝7.0Hz,3H),0.93(m,1H),0.65-0.56(m,1H),0.45-0.36(m,1H),0.21(m,1H)；
13C NMR(100MHz,CDCl3)：δ161.4,154.6,138.9,131.6,115.1,69.9,60.9,59.4,16.3,14.9,13.8,2.2；
IR(KBr)νmax：2973,1717,,1242,1101,983,901,767,623cm-1；
HRMS(ESI)Calcd for C13H16Br2NaO4[M+Na]+：416.9311,Found 416.9314；
in conclusion, the structural formula of the gem-dibromoalkenyl dihydrofurans synthesized in the example is as follows:
Figure BDA0003527550110000112
example 12:
a gem-dibromo alkenyl dihydrofuran compound, which is prepared by removing reaction raw material (5-triisopropyl silyl alkene) in the synthesis processAcetylenic ketone compound) is replaced by 1-propyl-2-ethoxyacyl (5-triisopropylsilyl) eneacetylenic ketone to 1-cyclobutyl-2-ethoxyacyl (5-triisopropylsilyl) eneacetylenic ketone
Figure BDA0003527550110000113
The same procedure as in example 10 was repeated except that the volume ratio of petroleum ether to ethyl acetate in the eluate was adjusted from 50:1 to 30: 1.
The yield of the geminal dibromoalkenyldihydrofurans in this example was 76%.
The nmr hydrogen spectrum of the synthesized gem-dibromoalkenyl dihydrofuran compound is shown in fig. 23, the nmr carbon spectrum is shown in fig. 24, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.28(s,1H),4.26(q,J＝7.1Hz,2H),3.44(dq,J＝9.1,7.1Hz,2H),3.27(dq,J＝9.1,7.0Hz,2H),3.09(p,J＝8.3Hz,1H),2.38-2.26(m,1H),2.05(m,1H),1.83-1.76(m,2H),1.71-1.58(m,2H),1.32(t,J＝7.1Hz,3H),1.17(t,J＝7.0Hz,3H)；
13C NMR(100MHz,CDCl3)：δ161.6,155.2,137.2,133.3,117.8,70.0,61.3,59.5,40.4,22.45,22.2,17.8,15.2,14.2；
IR(KBr)νmax：3394,2980,1721,1528,1236,773,682cm-1；
HRMS(ESI)Calcd for C14H18Br2NaO4[M+Na]+：430.9472,Found 430.9472；
In conclusion, the structural formula of the gem-dibromoalkenyl dihydrofurans synthesized in the example is as follows:
Figure BDA0003527550110000121
example 13:
a gem-dibromo alkenyl dihydrofuran compound is prepared from 1-propyl-2-ethoxy (5-triisopropyl) acyl (5-triisopropyl) as raw material through synthesizingSilyl) alkenone for 1-methyl-2-ethoxyacyl (5-triisopropylsilyl) alkenone
Figure BDA0003527550110000122
The same procedure as in example 10 was repeated except that the volume ratio of petroleum ether to ethyl acetate in the eluate was adjusted from 50:1 to 40: 1.
The yield of the geminal dibromoalkenyldihydrofurans in this example was 79%.
The nmr hydrogen spectrum of the synthesized gem-dibromoalkenyl dihydrofurans in the example is shown in fig. 25, the nmr carbon spectrum is shown in fig. 26, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.30(s,1H),4.31(q,J＝7.1Hz,2H),3.56-3.42(m,1H),3.37-3.22(m,1H),1.79(s,3H),1.36(t,J＝7.1Hz,3H),1.22(t,J＝7.0Hz,3H)；
13C NMR(100MHz,CDCl3)：δ161.6,154.6,138.8,132.6,115.4,70.6,61.3,59.4,24.67,15.2,14.2；
IR(KBr)νmax：3411,2928,1712,1387,1255,1088,955,741cm-1；
HRMS(ESI)Calcd for C11H14Br2NaO4[M+Na]+：390.9154,Found 390.9155；
in conclusion, the structural formula of the gem-dibromoalkenyl dihydrofurans synthesized in the example is as follows:
Figure BDA0003527550110000131
example 14:
during the synthesis process, except that 1-propyl-2-ethoxy acyl (5-triisopropyl silicon base) eneyne ketone is replaced by 1-propyl-2-ethoxy acyl (5-triisopropyl silicon base) eneyne ketone to 1-methyl-2-propoxy acyl (5-triisopropyl silicon base) eneyne ketone
Figure BDA0003527550110000132
The same procedure as in example 10 was repeated except that the volume ratio of petroleum ether to ethyl acetate in the eluate was adjusted from 50:1 to 20: 1.
The yield of the gem-dibromoalkenyldihydrofurans in this example was 79%.
The nmr hydrogen spectrum of the synthesized gem-dibromoalkenyl dihydrofuran compound is shown in fig. 27, the nmr carbon spectrum is shown in fig. 28, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CD3CN)：δ7.35-7.27(m,1H),4.18(t,J＝6.5Hz,2H),3.41(dq,J＝9.2,7.1Hz,1H),3.29(dq,J＝9.1,7.0Hz,1H),1.75-1.70(m,5H),1.14(t,J＝7.0Hz,3H),0.99(t,J＝7.4Hz,3H)；
13C NMR(100MHz,CD3CN)：δ162.01,155.6,139.8,132.8,116.1,70.0,67.3,59.9,24.8,22.3,15.2,10.4；
IR(KBr)νmax：3403,2926,1712,1387,1254,1161,955,740cm-1；
HRMS(ESI)Calcd for C12H16Br2NaO4[M+Na]+：404.9309,Found 404.9309；
in conclusion, the structural formula of the gem-dibromoalkenyl dihydrofuran compound synthesized in the embodiment is as follows:
Figure BDA0003527550110000133
example 15:
during the synthesis process, except that 1-propyl-2-ethoxy acyl (5-triisopropyl silicon base) eneyne ketone is replaced by 1-propyl-2-ethoxy acyl (5-triisopropyl silicon base) eneyne ketone to 1-methyl-2-butoxy acyl (5-triisopropyl silicon base) eneyne ketone
Figure BDA0003527550110000141
Adjusting the volume ratio of petroleum ether to ethyl acetate in the eluent from 50:1The procedure was repeated in the same manner as in example 10 except that the ratio was 30: 1.
The yield of the geminal dibromoalkenyldihydrofurans in this example was 82%.
The nmr hydrogen spectrum of the synthesized gem-dibromoalkenyl dihydrofuran compound in the example is shown in fig. 29, the nmr carbon spectrum is shown in fig. 30, and the resolution analysis (hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrum) is as follows:
1H NMR(400MHz,CDCl3)：δ7.29(s,1H),4.25(m,2H),3.54-3.42(m,1H),3.35-3.21(m,1H),1.78(s,3H),1.75-1.66(m,2H),1.52-1.40(m,2H),1.21(t,J＝7.0Hz,3H),0.98(t,J＝7.4Hz,3H)；
13C NMR(100MHz,CDCl3)：δ161.7,154.6,138.8,132.7,115.4,70.6,65.2,59.4,30.6,24.7,19.1,15.2,13.7；
IR(KBr)νmax：3416,2927,2929,1712,1388,1254,1088,954cm-1；
HRMS(ESI)Calcd for C13H18Br2NaO4[M+Na]+：418.9469,Found 418.9465；
In conclusion, the structural formula of the gem-dibromoalkenyl dihydrofuran compound synthesized in the embodiment is as follows:
Figure BDA0003527550110000142
the above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (10)

1. A synthetic method of a gem-dibromo alkenyl dihydrofuran compound is characterized by comprising the following steps: mixing the 5-triisopropyl silyl enealkynone compound and monohydric alcohol for reaction to obtain the gem-dibromo alkenyl dihydrofuran compound.
2. The method for synthesizing the gem-dibromoalkenyl dihydrofurans according to claim 1, comprising the following steps: dispersing a palladium catalyst, a ligand, N-bromosuccinimide and an additive in an organic solvent, adding a 5-triisopropyl silicon-based eneynone compound and monohydric alcohol, and reacting in a protective atmosphere to obtain the gem-dibromo alkenyl dihydrofuran compound.
3. The method for synthesizing a geminal dibromoalkenyl dihydrofuran compound as claimed in claim 1 or 2, wherein: the structural formula of the 5-triisopropylsilyl enynone compound is shown in the specification
Figure FDA0003527550100000011
In the formula, R1One selected from methyl, propyl, cyclopropyl and cyclobutyl, R2Is selected from one of acetyl, ethoxyacyl, propoxyl and butoxyacyl.
4. The method for synthesizing a geminal dibromoalkenyl dihydrofuran compound as claimed in claim 1 or 2, wherein: the monohydric alcohol is selected from one of methanol, ethanol, isoamyl alcohol, benzyl alcohol, 4-chlorobenzyl alcohol, 4-methylbenzyl alcohol, 6-chlorohexanol, 2-methoxyacetyl alcohol and 2-methoxyethanol.
5. The method for synthesizing a geminal dibromoalkenyl dihydrofuran compound as claimed in claim 1 or 2, wherein: the molar ratio of the 5-triisopropylsilyl enynone compound to the monohydric alcohol is 1: 3-6.
6. The method for synthesizing a geminal dibromoalkenyl dihydrofuran compound as claimed in claim 1 or 2, wherein: the reaction is carried out at normal temperature, and the reaction time is 6-8 h.
7. The method for synthesizing a geminal dibromoalkenyl dihydrofuran compound as claimed in claim 2, wherein: the palladium catalyst is at least one of palladium dichloride, bis-triphenylphosphine palladium dichloride and 1, 3-bis-diphenylphosphinopropane palladium dichloride.
8. The method for synthesizing a geminal dibromoalkenyl dihydrofuran compound as claimed in claim 2 or 7, wherein: the ligand is at least one selected from 1, 10-phenanthroline, 2-methyl-1, 10-phenanthroline, 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline.
9. The method for synthesizing a geminal dibromoalkenyl dihydrofuran compound as claimed in claim 2 or 7, wherein: the additive is a mixture of silver trifluoroacetate, potassium fluoride and crown ether.
10. The method for synthesizing a geminal dibromoalkenyl dihydrofuran compound as claimed in claim 2 or 7, wherein: the organic solvent is at least one of acetonitrile and tetrahydrofuran.
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Citations (2)

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CN111205277A (en) * 2018-11-22 2020-05-29 青岛博远高分子材料研究院有限公司 Use of organic small molecule fluorescent compounds in phototherapy
CN113336743A (en) * 2021-06-24 2021-09-03 青岛科技大学 Compound with active and passive dual targeting, and pharmaceutical composition and application thereof

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