CN117534596A - Method for preparing beta-sulfonyl methyl acrylate compound - Google Patents
Method for preparing beta-sulfonyl methyl acrylate compound Download PDFInfo
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- CN117534596A CN117534596A CN202210921269.8A CN202210921269A CN117534596A CN 117534596 A CN117534596 A CN 117534596A CN 202210921269 A CN202210921269 A CN 202210921269A CN 117534596 A CN117534596 A CN 117534596A
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- methanol
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- terminal alkyne
- methyl acrylate
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- 238000000034 method Methods 0.000 title claims abstract description 48
- BAPJBEWLBFYGME-UHFFFAOYSA-N acrylic acid methyl ester Natural products COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 title claims description 17
- 150000001345 alkine derivatives Chemical group 0.000 claims abstract description 20
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims abstract description 13
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 13
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 13
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 13
- 239000011734 sodium Substances 0.000 claims abstract description 13
- 239000012298 atmosphere Substances 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 59
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- 150000001875 compounds Chemical class 0.000 claims description 21
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 15
- -1 acrylate compound Chemical class 0.000 claims description 13
- 239000007800 oxidant agent Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 239000011630 iodine Substances 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 6
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- UNMYWSMUMWPJLR-UHFFFAOYSA-L Calcium iodide Chemical compound [Ca+2].[I-].[I-] UNMYWSMUMWPJLR-UHFFFAOYSA-L 0.000 claims description 3
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 3
- 229940046413 calcium iodide Drugs 0.000 claims description 3
- 229910001640 calcium iodide Inorganic materials 0.000 claims description 3
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 235000009518 sodium iodide Nutrition 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- 125000001424 substituent group Chemical group 0.000 claims 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 150000002496 iodine Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000004492 methyl ester group Chemical group 0.000 claims 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 239000002994 raw material Substances 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 4
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 230000003647 oxidation Effects 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 150000003254 radicals Chemical class 0.000 abstract description 3
- 229910052723 transition metal Inorganic materials 0.000 abstract description 3
- 150000003624 transition metals Chemical class 0.000 abstract description 3
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 238000001228 spectrum Methods 0.000 description 30
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- 239000001257 hydrogen Substances 0.000 description 15
- 238000001819 mass spectrum Methods 0.000 description 15
- 230000005311 nuclear magnetism Effects 0.000 description 15
- 239000007858 starting material Substances 0.000 description 15
- 230000000052 comparative effect Effects 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000005810 carbonylation reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- CHLCPTJLUJHDBO-UHFFFAOYSA-M sodium;benzenesulfinate Chemical compound [Na+].[O-]S(=O)C1=CC=CC=C1 CHLCPTJLUJHDBO-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- 229940005561 1,4-benzoquinone Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for preparing beta-sulfonyl methyl acrylate compounds. In particular to a one-pot method for preparing the terminal alkyne and the organic sodium sulfinate under the condition of oxidation in a carbon monoxide atmosphere. The invention starts from a substrate which is widely and commercially available, namely terminal alkyne and organic sodium sulfinate, and obtains a series of beta-sulfonyl methyl acrylate compounds through a free radical process under the conditions of oxidation and no need of transition metal catalysis.
Description
Technical Field
The invention relates to a method for synthesizing beta-sulfonyl methyl acrylate compounds.
Background
Beta-sulfonyl methyl acrylate is a very important chemical structural fragment because it is widely found in various natural products and modern drugs and has good biological activity. Furthermore, it is also a very important and valuable fragment in organic synthesis. The synthesis of methyl β -sulfonyl acrylate has been generally achieved by a multi-step reaction and requires the use of air-labile butyl lithium reagents. In recent years, the difunctional carbonylation reaction to produce polyfunctional carbonyl-containing compounds has become a promising approach.
Compared with the prior synthesis method of the beta-sulfonyl methyl acrylate compound, the method develops a difunctional carbonylation reaction of alkyne to synthesize the beta-sulfonyl methyl acrylate in one step. By using simple and easy-to-prepare terminal alkyne and organic sodium sulfinate, we can synthesize beta-sulfonyl methyl acrylate with a wide substrate in one step.
In summary, a process is described herein for obtaining a series of beta-methyl sulfonyl acrylate compounds via a free radical process under oxidizing conditions and without the need for transition metal catalysis.
Disclosure of Invention
The invention aims to provide a method for synthesizing a beta-sulfonyl methyl acrylate derivative.
Reaction equation 1: synthesis of beta-sulfonyl methyl acrylate derivatives wherein the wavy line represents a trans or cis structure linkage;
the specific operation steps are as follows (reaction equation 1):
performing reaction in a high-pressure reaction kettle, weighing oxidant, iodized salt, terminal alkyne 1 and organic sodium sulfinate 2, and reacting at 90-150 ℃ in a carbon monoxide atmosphere under 10-60 atm, preferably 130 ℃; the reaction time is 10.0 to 24.0 hours, preferably 20.0 hours; after the reaction is finished, separating to obtain the beta-sulfonyl methyl acrylate compound 3.
The molar ratio of the terminal alkyne 1 to the organic sodium sulfinate 2 compound is 1:1.0-3.0, preferably 1:1.5-2.5, more preferably 1:2.0.
The carbon monoxide gas pressure is 10 to 60 atmospheres, preferably 40 to 45 atmospheres.
The solvent is one or more of 1, 2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide, 1, 4-dioxane, acetonitrile, methanol, and methanol-water mixture, preferably methanol-water mixture (methanol and water volume ratio is 0.5-5:1, preferably 3-5:1, more preferably 3.5-4:1); the solvent is used in an amount of 1.0 to 5.0 ml, preferably 2.0 ml, per 0.2mmol of terminal alkyne 1.
The oxidant is one or more than two of potassium persulfate, sodium persulfate, ammonium persulfate, and potassium peroxymonosulfonate, preferably sodium persulfate; the amount of the oxidizing agent used is 2 to 4 times, preferably 2.2 to 2.5 times, the number of moles of the terminal alkyne 1.
The iodine-containing salt is one or more of potassium iodide, sodium iodide, lithium iodide, calcium iodide, tetrabutylammonium iodide, and elemental iodine, preferably potassium iodide; the amount of the iodine-containing salt is 1 to 3 times, preferably 1.1 to 1.5 times the mole number of the terminal alkyne 1.
The invention starts from a substrate which is widely and commercially available, namely terminal alkyne and organic sodium sulfinate, and obtains a series of beta-sulfonyl methyl acrylate compounds through a free radical process under the conditions of oxidation and no need of transition metal catalysis.
The invention has the following advantages:
firstly, the reaction does not need to use metal reagents such as n-butyllithium and the like to synthesize the beta-sulfonyl methyl acrylate derivative, thereby greatly expanding the substrate range. Second, all the compounds including aryl terminal alkyne, alkyl terminal alkyne, sodium aryl sulfinate and sodium alkyl sulfinate can be converted in the reaction, so that the applicability of the reaction is widened. Thirdly, the beta-sulfonyl methyl acrylate is prepared by a one-pot method in one step, and the reaction steps are reduced.
Detailed Description
For a better understanding of the present invention, it is illustrated by the following examples. The starting materials and results for examples 1-14 are shown in Table 1.
TABLE 1 reaction results of different substituted terminal alkynes 1 and organic sodium sulfinate 2
Example 1
The reaction was carried out in a autoclave, first phenylacetylene 1a (0.2 mmol), sodium phenylsulfinate 2a (0.4 mmol), sodium persulfate (0.44 mmol) and potassium iodide (0.22 mmol) were added to a 4 ml glass vial, magneton was added, and 2.0 ml methanol/water volume ratio was 4:1, tightly covering the bottle mouth of a small glass bottle by using a rubber bottle cap, inserting one end of a needle point of a syringe needle into the small bottle through the bottle cap to enable the small bottle to be communicated with the outside through the needle, putting the reaction small bottle into a high-pressure reaction kettle, enabling the inside of the small bottle to be communicated with the inside of the outside reaction kettle through the needle, replacing carbon monoxide with the high-pressure reaction kettle, filling carbon monoxide with 40 atmospheres to enable the inside of the high-pressure reaction kettle to rise to 40 atmospheres, enabling the carbon monoxide in the kettle to be communicated with the inside of the small bottle through the needle at the moment, stirring and reacting at 130 ℃ for 20.0 hours; after the reaction was completed, the yield of the beta-sulfonyl methyl acrylate compound 3a was 68% by separation by column chromatography, wherein the trans structure/cis structure ratio (molar ratio, the same applies hereinafter) was 3:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
The detection data are as follows:
3a yellow oil (41 mg, 68%). 1 H NMR(700MHz,Chloroform-d)δ7.98–7.92(m,0.65H),7.51(s,1.00H),7.48(dd,J＝8.4,1.5Hz,2.31H),7.46–7.44(m,1.02H),7.36–7.31(m,1.60H),7.29(tt,J＝7.4,1.6Hz,2.96H),7.22(dd,J＝8.5,7.0Hz,1.96H),7.08–7.03(m,1.95H),6.55(s,0.34H)3.94(s,1.01H),3.69(s,3.00H). 13 C NMR(176MHz,CDCl3)δ166.5,165.5,146.1,143.1,140.5,140.2,139.7,133.9,133.7,132.1,131.3,130.8,129.4,129.4,129.3,129.2,129.0,128.0,127.8,127.0,126.5,53.4,53.2.HRMS(ESI-TOF)m/z:[M+H]+Calcd for C 16 H 14 O 4 S 303.0686；Found:303.0685.
Example 2
The procedure and conditions were as in example 1, except that the yields of starting materials 1 and/or 2,3b from Table 1 were 55%, with a trans structure/cis structure ratio of 10:3, identifying the structure of the compound through nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum.
Example 3
The procedure and conditions were as in example 1, except that the yields of starting materials 1 and/or 2,3c from Table 1 were 50% and the trans structure/cis structure ratio was 15:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
Example 4
The procedure and conditions were as in example 1, except that starting material 1 and/or 2,3d yields of Table 1 were 49%, with a trans structure/cis structure ratio of greater than 20:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
Example 5
The procedure and conditions were as in example 1, except that starting material 1 and/or 2,3e yields of Table 1 were 55%, with a trans structure/cis structure ratio of 10:3, identifying the structure of the compound through nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum.
Example 6
The procedure and conditions were as in example 1, except that starting material 1 and/or 2,3f yields of Table 1 were 60%, with a trans structure/cis structure ratio of 20:3, identifying the structure of the compound through nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum.
Example 7
The procedure and conditions were as in example 1, except that starting materials 1 and/or 2,3g yield from Table 1 were 67%, with a trans structure/cis structure ratio of 10:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
Example 8
The procedure and conditions were as in example 1, except that starting material 1 and/or 2,3h yields of Table 1 were 82% and the trans structure/cis structure ratio was 5:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
Example 9
The procedure and conditions were as in example 1, except that the yields of starting materials 1 and/or 2,3i of Table 1 were 58% and the trans structure/cis structure ratio was 5:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
Example 10
The procedure and conditions were as in example 1, except that starting material 1 and/or 2,3j yields of Table 1 were 45% with a trans structure/cis structure ratio of 4:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
Example 11
The procedure and conditions were as in example 1, except that starting material 1 and/or 2,3k yields of Table 1 were 67% and the trans structure/cis structure ratio was 5:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
Example 12
The procedure and conditions were as in example 1, except that starting materials 1 and/or 2,3l yields of Table 1 were 43% and the trans structure/cis structure ratio was greater than 20:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
Example 13
The procedure and conditions are as in example 1, except that starting material 1 and/or 2,3m yields of table 1 are 50% with a trans structure/cis structure ratio of greater than 20:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
Example 14
The procedure and conditions are as in example 1, except that starting material 1 and/or 2,3n yields of Table 1 are 31% and the trans structure/cis structure ratio is greater than 20:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
Application example 1:
reaction equation 2: synthesis of methyl beta-sulfonyl acrylate
Product 3a can be synthesized in one step by this reaction, while 3a is a building block in organic chemistry of relatively great importance (known compounds, which require multi-step synthesis in the literature, and also involve the use of n-butyllithium, reference can be made to S.Paul and J.Guin, green chem.,2017,19,2530-2534. 1w of compounds in this document). The specific operation is as follows:
the reaction was carried out in a autoclave, first phenylacetylene 1a (0.2 mmol), sodium phenylsulfinate 2a (0.4 mmol), sodium persulfate (0.44 mmol) and potassium iodide (0.22 mmol) were added to a 4 ml glass vial, magneton was added, and 2.0 ml methanol/water volume ratio was 4:1, tightly covering the bottle mouth of a small glass bottle by using a rubber bottle cap, inserting one end of a needle point of a syringe needle into the small bottle through the bottle cap to enable the small bottle to be communicated with the outside through the needle, putting the reaction small bottle into a high-pressure reaction kettle, enabling the inside of the small bottle to be communicated with the inside of the outside reaction kettle through the needle, replacing carbon monoxide with the high-pressure reaction kettle, filling carbon monoxide with 40 atmospheres to enable the inside of the high-pressure reaction kettle to rise to 40 atmospheres, enabling the carbon monoxide in the kettle to be communicated with the inside of the small bottle through the needle at the moment, stirring and reacting at 130 ℃ for 20.0 hours; after the reaction, separating by column chromatography to obtain the beta-sulfonyl methyl acrylate compound 3a with the yield of 68%, wherein the ratio of the trans structure to the cis structure is 3:1, the compound is subjected to nuclear magnetism (hydrogen spectrum and carbon spectrum) and high-resolution mass spectrum identification.
3a yellow oil (41 mg, 68%). 1 H NMR(700MHz,Chloroform-d)δ7.98–7.92(m,0.65H),7.51(s,1.00H),7.48(dd,J＝8.4,1.5Hz,2.31H),7.46–7.44(m,1.02H),7.36–7.31(m,1.60H),7.29(tt,J＝7.4,1.6Hz,2.96H),7.22(dd,J＝8.5,7.0Hz,1.96H),7.08–7.03(m,1.95H),6.55(s,0.34H)3.94(s,1.01H),3.69(s,3.00H). 13 C NMR(176MHz,CDCl3)δ166.5,165.5,146.1,143.1,140.5,140.2,139.7,133.9,133.7,132.1,131.3,130.8,129.4,129.4,129.3,129.2,129.0,128.0,127.8,127.0,126.5,53.4,53.2.HRMS(ESI-TOF)m/z:[M+H]+Calcd for C 16 H 14 O 4 S 303.0686；Found:303.0685.
Example 15
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1) except that the oxidizing agent of the reaction was changed to equimolar potassium persulfate, and the yield of the objective β -sulfonylmethyl acrylate compound was 61%.
Example 16
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1) except that the oxidizing agent for the reaction was changed to equimolar ammonium persulfate, and the yield of the objective β -sulfonyl methyl acrylate compound was 41%.
Example 17
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the pressure of the reacted carbon monoxide was reduced to 10 atm, and the yield of the objective β -sulfonylmethyl acrylate compound was reduced to 23%.
Example 18
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the pressure of the reacted carbon monoxide was reduced to 20 atm, and the yield of the objective β -sulfonylmethyl acrylate compound was reduced to 52%.
Example 19
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1) except that the iodine-containing salt of the reaction was changed to equimolar calcium iodide, and the yield of the objective β -sulfonylmethyl acrylate compound was 13%.
Example 20
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1) except that the iodine-containing salt of the reaction was changed to equimolar tetrabutylammonium iodide, and the yield of the objective β -sulfonylmethyl acrylate compound was 33%.
Example 21
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the solvent of the reaction was changed to methanol/water=1: 1, the yield of the target product beta-sulfonyl methyl acrylate compound will be 25%.
Example 22
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the solvent of the reaction was methanol/water=1: 1, the yield of the target product beta-sulfonyl methyl acrylate compound will be 25%.
Example 23
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that 4.0 ml of the solvent was used, and the yield of the objective β -sulfonylmethyl acrylate compound was reduced to 40%.
Comparative example 1
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the temperature of the reaction was lowered to 50 degrees celsius and the yield of the target product β -sulfonylmethyl acrylate compound was lowered to 1%.
Comparative example 2
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the reaction time was reduced to 5 hours, the yield of the objective β -sulfonylmethyl acrylate compound was reduced to 10%, and the starting material was not sufficiently converted.
Comparative example 3
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the iodinated salt of the reaction was removed, the yield of the objective beta-methyl sulfonyl acrylate compound was reduced to 0%,
comparative example 4
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the reaction was carried out with the oxidizing agent removed, and the yield of the objective β -sulfonylmethyl acrylate compound was reduced to 0%.
Comparative example 5
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the oxidizing agent was replaced with equimolar 1, 4-benzoquinone, and the yield of the objective β -sulfonylmethyl acrylate compound was reduced to 0%.
Comparative example 6
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the oxidizing agent was replaced with equimolar silver carbonate, and the yield of the objective β -sulfonyl methyl acrylate compound was reduced to 0%.
Comparative example 7
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1) except that the solvent was changed to pure water and the yield of the objective β -sulfonylmethyl acrylate compound was 0%.
Comparative example 8
The other reaction conditions set forth in example 1 were kept unchanged (i.e., the procedure and conditions were the same as in example 1), except that the solvent was changed to pure methanol, and the yield of the target product β -sulfonylmethyl acrylate compound was 0%.
Claims (7)
1. A method for preparing beta-sulfonyl methyl acrylate compounds is characterized in that:
the beta-sulfonyl methyl acrylate derivative 3 is produced by taking terminal alkyne 1 and organic sodium sulfinate 2 shown in the following formula as raw materials, wherein the reaction formula is as follows:
R 1 is one or more of 3-thienyl, n-hexyl, phenyl or substituted phenyl, wherein the substituent on the benzene ring of the substituted phenyl comprises methyl, tertiary butyl, fluorine atom, chlorine atom, bromine atom, formic acidOne to five, preferably 1 to 2, methyl ester groups and trifluoromethoxy groups, and 1 to 5, preferably 1 to 2 substituents;
R 2 is one or more of phenyl, 4-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, ethyl and methyl.
2. The method for producing a beta-sulfonylmethyl acrylate compound according to claim 1, characterized in that:
the specific operation steps are as follows:
performing reaction in a high-pressure reaction kettle, weighing oxidant, iodized salt, terminal alkyne 1, organic sodium sulfinate 2 and a solvent containing methanol, placing the oxidant, the iodine salt, the terminal alkyne 1, the organic sodium sulfinate 2 and the solvent containing methanol in the high-pressure reaction kettle, and replacing the atmosphere in the reaction kettle with a carbon monoxide atmosphere under 10-60 atm, and performing reaction at 90-150 ℃, preferably 130-140 ℃; the reaction time is 10.0 to 24.0 hours, preferably 20.0 to 24.0 hours; after the reaction is finished, separating to obtain the beta-sulfonyl methyl acrylate compound 3.
3. A method according to claim 1 or 2, characterized in that:
the molar ratio of the terminal alkyne 1 to the organic sodium sulfinate 2 compound is 1:1.0-3.0, preferably 1:1.5-2.5, more preferably 1:2.0.
4. A method according to claim 1 or 2, characterized in that:
the carbon monoxide gas pressure is 10 to 60 atmospheres, preferably 40 to 45 atmospheres.
5. A method according to claim 1 or 2, characterized in that:
the solvent containing methanol is a mixture of methanol and other solvents, the other solvents are one or more than two of 1, 2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide, 1, 4-dioxane, acetonitrile and water, the mixture of methanol and other solvents is preferably a mixture of methanol and water, and the volume ratio of methanol to other solvents (preferably water) is 0.5-5:1, preferred range 3-5:1, more preferably 3.5-4:1, a step of;
the amount of the methanol-containing solvent used is 1.0 to 5.0 ml, preferably 2.0 ml, per 0.2mmol of the terminal alkyne 1.
6. A method according to claim 1 or 2, characterized in that:
the oxidant is one or more than two of potassium persulfate, sodium persulfate, ammonium persulfate, and potassium peroxymonosulfonate, preferably sodium persulfate; the amount of the oxidizing agent used is 2 to 4 times, preferably 2.2 to 2.5 times, the number of moles of the terminal alkyne 1.
7. A method according to claim 1 or 2, characterized in that:
the iodine-containing salt is one or more of potassium iodide, sodium iodide, lithium iodide, calcium iodide, tetrabutylammonium iodide, and elemental iodine, preferably potassium iodide; the amount of the iodine-containing salt is 1 to 3 times, preferably 1.1 to 1.5 times the mole number of the terminal alkyne 1.
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