CN115403505A - A kind of preparation method of the thioester compound containing indolinone structure - Google Patents
A kind of preparation method of the thioester compound containing indolinone structure Download PDFInfo
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- -1 thioester compound Chemical class 0.000 title claims abstract description 53
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical group C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 13
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical group C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052750 molybdenum Inorganic materials 0.000 claims abstract description 9
- 239000011733 molybdenum Substances 0.000 claims abstract description 9
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims abstract description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims abstract description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 claims abstract description 6
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 229910052763 palladium Inorganic materials 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 5
- 239000003446 ligand Substances 0.000 claims 3
- 239000003513 alkali Substances 0.000 claims 2
- 239000002585 base Substances 0.000 claims 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract description 7
- 229910052717 sulfur Inorganic materials 0.000 abstract description 7
- 239000011593 sulfur Substances 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 5
- 239000003638 chemical reducing agent Substances 0.000 abstract description 4
- 238000010276 construction Methods 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000001514 detection method Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000005810 carbonylation reaction Methods 0.000 description 4
- 238000005936 thiocarbonylation reaction Methods 0.000 description 4
- 230000007704 transition Effects 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910005948 SO2Cl Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
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- Chemical & Material Sciences (AREA)
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Abstract
本发明公开了一种含有吲哚酮结构的硫酯化合物的制备方法，包括如下步骤：将醋酸钯，三环己基膦，羰基钼、碳酸铯、水、碘代芳烃以及磺酰氯化合物于100℃进行反应24小时，反应完全后，后处理得到所述的含有吲哚酮结构的硫酯化合物。该反应原料廉价易得，底物适用性好，反应效率高，同时以羰基钼既作为羰基来源又作为还原剂，操作简单。此外，该方法以磺酰氯化合物作为硫源，为含有吲哚酮结构的硫酯化合物的构建提供了新的途径。The invention discloses a preparation method of a thioester compound containing an indolone structure, which comprises the following steps: preparing palladium acetate, tricyclohexylphosphine, molybdenum carbonyl, cesium carbonate, water, iodoarene and sulfonyl chloride at 100°C The reaction was carried out for 24 hours. After the reaction was complete, post-treatment was carried out to obtain the thioester compound containing the indolinone structure. The reaction raw material is cheap and easy to obtain, the substrate applicability is good, and the reaction efficiency is high. At the same time, molybdenum carbonyl is used as both a carbonyl source and a reducing agent, and the operation is simple. In addition, this method uses sulfonyl chloride compounds as sulfur sources, which provides a new way for the construction of thioester compounds containing indolinone structures.
Description
技术领域technical field
本发明属于有机合成领域，尤其涉及一种含有吲哚酮结构的硫酯化合物的制备方法。The invention belongs to the field of organic synthesis, in particular to a preparation method of a thioester compound containing an indolinone structure.
背景技术Background technique
吲哚酮是一类十分重要的杂环分子，广泛存在于各种天然产物、生物活性分子和药物中(Eur.J.Med.Chem.2021,216,113334)。此外，作为关键的反应中间体，吲哚酮在有机合成中有着非常广泛的应用。因此，多种合成吲哚酮的方法被开发出来。其中最具有吸引力的方法是基于过渡金属催化的级联环化反应，因为在反应中生成的有机金属络合物可以通过进一步的转化来合成官能团化的吲哚酮衍生物。Indolinones are a very important class of heterocyclic molecules that widely exist in various natural products, bioactive molecules and drugs (Eur.J.Med.Chem.2021, 216, 113334). In addition, as a key reaction intermediate, indolinone has a very wide range of applications in organic synthesis. Therefore, various methods for synthesizing indolinones have been developed. Among them, the most attractive approach is based on transition metal-catalyzed cascade cyclization reactions, because the organometallic complexes generated in the reaction can be further transformed to synthesize functionalized indolinone derivatives.
近年来，过渡金属催化的羰基化反应作为合成含羰基化合物的重要方法在学术和工业领域都取得了重大的进展(Chem 2019,5,526)。吲哚酮衍生物也同样能够通过过渡金属催化的环化/羰基化反应来构建。在这些反应中，含有吲哚酮结构的硫酯化合物的合成引起了广泛的关注，因为硫酯化合物被认为是生命科学和合成化学中具有独特化学性质的一类有机化合物。然而，有关合成含有吲哚酮结构的硫酯化合物的报道却非常有限。因此，探索更多的反应途径来构建含有吲哚酮结构的硫酯化合物是十分必要的。In recent years, transition metal-catalyzed carbonylation reactions, as an important method for the synthesis of carbonyl-containing compounds, have made significant progress in both academic and industrial fields (Chem 2019, 5, 526). Indolinone derivatives can also be constructed by transition metal-catalyzed cyclization/carbonylation reactions. Among these reactions, the synthesis of thioester compounds containing indolinone structures has attracted extensive attention because thioester compounds are considered as a class of organic compounds with unique chemical properties in life sciences and synthetic chemistry. However, reports on the synthesis of thioester compounds containing indolinone structures are very limited. Therefore, it is necessary to explore more reaction pathways to construct thioester compounds containing indolinone structure.
近年来，过渡金属催化的硫羰基化反应已成为合成硫酯化合物的重要手段。在大多数硫羰基化反应中，通常使用硫醇作为硫源，硫醇由于其对过渡金属的强亲硫性，容易使催化剂中毒，使该类反应具有一定的局限性(Chem.Rev.1989,89,1)。因此，开发基于替代硫源的羰基化反应仍然是化学家们工作的重点之一。磺酰氯作为一类廉价易得、操作简单的化学试剂，在有机合成中有着非常重要的应用。近年来，我们团队开发了一系列以磺酰氯作为硫源的硫羰基化反应。因此，在前期工作的基础上，我们发展了钯催化的环化/硫羰基化反应来合成含有吲哚酮结构的硫酯化合物。值得注意的是，磺酰氯在反应中作为重要的硫源，不论是芳基还是烷基取代的磺酰氯都可以很好的兼容该反应。同时羰基钼既作为羰源又作为还原剂，使该方法有着良好的应用前景。In recent years, transition metal-catalyzed thiocarbonylation has become an important method for the synthesis of thioester compounds. In most thiocarbonylation reactions, mercaptans are usually used as sulfur sources, and mercaptans are likely to poison the catalyst due to their strong thiolophilicity to transition metals, which makes this type of reaction have certain limitations (Chem.Rev.1989 ,89,1). Therefore, the development of carbonylation reactions based on alternative sulfur sources is still one of the priorities of chemists. Sulfonyl chloride, as a class of chemical reagents that are cheap, easy to obtain and easy to operate, has a very important application in organic synthesis. In recent years, our group has developed a series of thiocarbonylation reactions using sulfuryl chloride as a sulfur source. Therefore, on the basis of previous work, we developed a palladium-catalyzed cyclization/thiocarbonylation reaction to synthesize thioester compounds containing indolinone structure. It is worth noting that sulfonyl chloride is an important sulfur source in the reaction, and both aryl and alkyl substituted sulfonyl chlorides are well compatible with the reaction. At the same time, molybdenum carbonyl acts as both carbonyl source and reducing agent, which makes this method have a good application prospect.
发明内容Contents of the invention
本发明提供了一种含有吲哚酮结构的硫酯化合物的制备方法，该反应原料廉价易得，底物适用性好，反应效率高，同时以羰基钼既作为羰基来源又作为还原剂，操作简单。此外，该方法以磺酰氯化合物作为硫源，为含有吲哚酮结构的硫酯化合物的构建提供了新的途径，并突出了磺酰氯化合物在羰基化反应中的应用。The invention provides a method for preparing a thioester compound containing an indolone structure. The reaction raw material is cheap and easy to obtain, the substrate applicability is good, and the reaction efficiency is high. At the same time, molybdenum carbonyl is used as both a carbonyl source and a reducing agent. Simple. In addition, this method uses sulfonyl chloride compounds as sulfur sources, which provides a new way for the construction of thioester compounds containing indolinone structures, and highlights the application of sulfonyl chloride compounds in carbonylation reactions.
一种含有吲哚酮结构的硫酯化合物的制备方法，包括如下步骤：将钯催化剂、三环己基膦、羰基钼、碳酸铯、水、碘代芳烃以及磺酰氯化合物于90～110℃反应20～28小时，反应完全后，后处理得到所述的含有吲哚酮结构的硫酯化合物；A preparation method of a thioester compound containing an indolinone structure, comprising the steps of: reacting a palladium catalyst, tricyclohexylphosphine, molybdenum carbonyl, cesium carbonate, water, iodoarene and a sulfonyl chloride compound at 90-110°C for 20 After ~28 hours, after the reaction is complete, the post-treatment obtains the thioester compound containing the indolinone structure;
所述的碘代芳烃的结构如式(II)所示：The structure of described iodoarene is shown in formula (II):
所述的磺酰氯化合物的结构如式(III)所示：The structure of the sulfonyl chloride compound is shown in formula (III):
R4-SO2Cl (III)；R4 - SO2Cl (III);
所述的含有吲哚酮结构的硫酯化合物的结构如式(I)所示：The structure of the described thioester compound containing indolinone structure is shown in formula (I):
式(Ⅰ)～(III)中，R1为H，C1～C4烷基，三氟甲基或卤素；In formulas (I) to (III), R 1 is H, C 1 to C 4 alkyl, trifluoromethyl or halogen;
R2为C1～C4烷基或对甲苯磺酰基；R 2 is C 1 -C 4 alkyl or p-toluenesulfonyl;
R3为H或C1～C7烃基；R 3 is H or C 1 -C 7 hydrocarbon group;
R4为C1～C6烷基、C1～C6环烷基或取代的苯基，所述苯基上的取代基为C1～C4烷基，甲氧基，苯基。R 4 is C 1 -C 6 alkyl, C 1 -C 6 cycloalkyl or substituted phenyl, and the substituent on the phenyl is C 1 -C 4 alkyl, methoxy, phenyl.
所述的钯催化剂、三环己基膦和碳酸铯的摩尔比为0.01:0.04:0.3；The mol ratio of described palladium catalyst, tricyclohexylphosphine and cesium carbonate is 0.01:0.04:0.3;
R1的取代位置为对位和间位。The substitution positions of R 1 are para-position and meta-position.
反应式如下：The reaction formula is as follows:
本发明中，可选用的后处理过程包括：过滤，硅胶拌样，最后经过柱层析纯化得到相应的含有吲哚酮结构的硫酯化合物，采用柱层析纯化为本领域常用的技术手段。In the present invention, the optional post-treatment process includes: filtration, sample mixing with silica gel, and finally purification by column chromatography to obtain the corresponding thioester compound containing an indolinone structure. Purification by column chromatography is a commonly used technical means in the field.
作为优选，R1为H，甲基，叔丁基，三氟甲基，F或Br；R2为甲基，乙基，正丁基或对甲苯磺酰基；R3为甲基或苄基。此时，所述的碘代芳烃容易得到，并且反应的产率较高。As preferred, R1 is H, methyl, tert - butyl, trifluoromethyl, F or Br; R2 is methyl, ethyl, n - butyl or p-toluenesulfonyl; R3 is methyl or benzyl . At this time, the iodoarene is easy to obtain, and the yield of the reaction is relatively high.
作为优选，R4为环己基，取代的苯基，所述苯基上的取代基为甲基，异丙基，叔丁基，甲氧基或苯基。此时，所述的磺酰氯化合物容易得到，并且反应的产率较高。Preferably, R 4 is cyclohexyl, substituted phenyl, and the substituent on the phenyl is methyl, isopropyl, tert-butyl, methoxy or phenyl. At this time, the sulfonyl chloride compound is easy to obtain, and the yield of the reaction is relatively high.
所述的用来制备含有吲哚酮结构的硫酯化合物的碘代芳烃和磺酰氯化合物价格较便宜，在自然界中广泛存在，作为优选，以摩尔量计，碘代芳烃：磺酰氯化合物：钯催化剂＝1:1～1.5:0.05～0.1；作为进一步的优选，以摩尔量计，碘代芳烃：磺酰氯化合物：钯催化剂＝1:1.5:0.05。The described iodoarenes and sulfonyl chloride compounds used to prepare the thioester compounds containing the indolinone structure are cheaper and widely exist in nature. As preferred, in molar weight, iodoarenes: sulfonyl chloride compounds: palladium Catalyst=1:1～1.5:0.05～0.1; as a further preference, in terms of molar weight, iodoarene:sulfonyl chloride compound:palladium catalyst=1:1.5:0.05.
作为优选，所述的反应的时间为24小时，反应时间过长增加反应成本，相反则难以保证反应的完全。Preferably, the reaction time is 24 hours, if the reaction time is too long, the reaction cost will be increased, and on the contrary, it is difficult to ensure the completeness of the reaction.
作为优选，反应在N,N-二甲基甲酰胺中进行，所述的N,N-二甲基甲酰胺的用量能将原料较好的溶解即可，0.2mmol的碘代芳烃使用的N,N-二甲基甲酰胺的量约为1～2mL。As a preference, the reaction is carried out in N,N-dimethylformamide, the amount of N,N-dimethylformamide can dissolve the raw materials well, and the N , The amount of N-dimethylformamide is about 1-2 mL.
作为优选，所述的钯催化剂为醋酸钯，在众多钯催化剂中醋酸钯价格比较便宜，而且使用醋酸钯为催化剂时反应效率较高。As a preference, the palladium catalyst is palladium acetate, and the price of palladium acetate is relatively cheap among many palladium catalysts, and the reaction efficiency is higher when palladium acetate is used as the catalyst.
作为进一步的优选，所述的含有吲哚酮结构的硫酯化合物为式(I-1)-式(I-5)所示化合物中的一种：As a further preference, the described thioester compound containing indolinone structure is one of the compounds shown in formula (I-1)-formula (I-5):
上述制备方法中，所述的醋酸钯、三环己基膦以及碳酸铯一般采用市售产品，都能从市场上方便地得到。In the above preparation method, the palladium acetate, tricyclohexylphosphine and cesium carbonate are generally commercially available products, which can be easily obtained from the market.
同现有技术相比，本发明的有益效果体现在：该反应原料廉价易得，制备方法简单，易于操作，后处理简便，底物官能团兼容性强，反应效率高。该方法以磺酰氯化合物作为硫源，以羰基钼既作为羰基来源又作为还原剂，为含有吲哚酮结构的硫酯化合物的构建提供了新的途径。可根据实际需要合成多种含有吲哚酮结构的硫酯化合物，实用性较强。Compared with the prior art, the beneficial effect of the present invention is reflected in that the reaction raw materials are cheap and easy to obtain, the preparation method is simple, the operation is easy, the aftertreatment is simple, the functional group compatibility of the substrate is strong, and the reaction efficiency is high. The method uses the sulfonyl chloride compound as the sulfur source, and the molybdenum carbonyl as both the carbonyl source and the reducing agent, which provides a new way for the construction of the thioester compound containing the indolinone structure. A variety of thioester compounds containing indolinone structure can be synthesized according to actual needs, which is more practical.
具体实施方式Detailed ways
下面结合具体实施例对本发明做进一步的描述。The present invention will be further described below in conjunction with specific embodiments.
实施例1～15Examples 1-15
按照表1的原料配比在15mL的封管中加入醋酸钯、三环己基膦、羰基钼、碳酸铯、水、碘代芳烃(II)和磺酰氯化合物(III)，然后加入N,N-二甲基甲酰胺(1mL)，混合搅拌均匀，按照表2的反应条件反应，反应完成后，过滤，硅胶拌样，经过柱层析纯化得到相应的含有吲哚酮结构的硫酯化合物(Ⅰ)，反应过程如下式所示：Add palladium acetate, tricyclohexylphosphine, molybdenum carbonyl, cesium carbonate, water, iodoarene (II) and sulfuryl chloride compound (III) into a 15mL sealed tube according to the raw material ratio in Table 1, and then add N,N- Dimethylformamide (1mL), mixed and stirred evenly, reacted according to the reaction conditions in Table 2, after the reaction was completed, filtered, sample mixed with silica gel, and purified by column chromatography to obtain the corresponding thioester compound (Ⅰ) containing the indolinone structure ), the reaction process is shown in the following formula:
表1实施例1～15的原料加入量The raw material addition of table 1 embodiment 1～15
表2Table 2
表1和表2中，T为反应温度，t为反应时间，Me为甲基，Bu为正丁基，Cy为环己基，CF3为三氟甲基，iPr为异丙基，tBu为叔丁基，OMe为甲氧基，Ph为苯基，Et为乙基，Ts为对甲苯磺酰基，Bn为苄基。In Table 1 and Table 2, T is the reaction temperature, t is the reaction time, Me is methyl, Bu is n - butyl, Cy is cyclohexyl, CF is trifluoromethyl, iPr is isopropyl, tBu is tertiary Butyl, OMe is methoxy, Ph is phenyl, Et is ethyl, Ts is p-toluenesulfonyl, Bn is benzyl.
实施例1～5制备得到化合物的结构确认数据：The structural confirmation data of the compounds prepared in Examples 1-5:
由实施例1制备得到的含有吲哚酮结构的硫酯化合物(I-1)的核磁共振(1H NMR和13C NMR)检测数据为：The nuclear magnetic resonance ( 1 H NMR and 13 C NMR) detection data of the thioester compound (I-1) containing the indolinone structure prepared in Example 1 is:
1H NMR(400MHz,CDCl3)δ7.28–7.24(m,2H),7.12(d,J＝8.1Hz,2H),7.07–7.03(m,3H),6.82(d,J＝8.0Hz,1H),3.27(d,J＝16.0Hz,1H),3.25–3.19(m,4H),2.31(s,3H),1.40(s,3H). 1 H NMR (400MHz, CDCl 3 ) δ7.28–7.24(m,2H),7.12(d,J=8.1Hz,2H),7.07–7.03(m,3H),6.82(d,J=8.0Hz, 1H), 3.27(d, J=16.0Hz, 1H), 3.25–3.19(m, 4H), 2.31(s, 3H), 1.40(s, 3H).
13C NMR(101MHz,CDCl3)δ193.9,179.3,143.4,139.7,134.3,132.2,129.9,128.1,123.6,122.8,122.3,108.2,49.7,46.2,26.4,24.1,21.3. 13 C NMR (101MHz, CDCl 3 ) δ193.9, 179.3, 143.4, 139.7, 134.3, 132.2, 129.9, 128.1, 123.6, 122.8, 122.3, 108.2, 49.7, 46.2, 26.4, 24.1, 21.3.
由实施例2制备得到的含有吲哚酮结构的硫酯化合物(I-2)的核磁共振(1H NMR和13C NMR)检测数据为：The nuclear magnetic resonance ( 1 H NMR and 13 C NMR) detection data of the thioester compound (I-2) containing the indolinone structure prepared in Example 2 is:
1H NMR(400MHz,CDCl3)δ7.27–7.22(m,2H),7.12(d,J＝8.1Hz,2H),7.06(d,J＝8.2Hz,2H),7.02(t,J＝7.5Hz,1H),6.83(d,J＝7.8Hz,1H),3.77–3.62(m,2H),3.25–3.16(m,2H),2.31(s,3H),1.69–1.62(m,2H),1.40–1.35(m,5H),0.93(t,J＝7.4Hz,3H). 1 H NMR (400MHz, CDCl 3 ) δ7.27–7.22(m, 2H), 7.12(d, J=8.1Hz, 2H), 7.06(d, J=8.2Hz, 2H), 7.02(t, J= 7.5Hz,1H),6.83(d,J=7.8Hz,1H),3.77–3.62(m,2H),3.25–3.16(m,2H),2.31(s,3H),1.69–1.62(m,2H ),1.40–1.35(m,5H),0.93(t,J＝7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ193.7,179.1,142.8,139.6,134.3,132.4,129.9,128.0,123.9,123.1,122.0,108.5,49.6,46.2,39.9,29.4,24.2,21.2,20.1,13.7. 13 C NMR (101MHz, CDCl 3 ) δ193.7, 179.1, 142.8, 139.6, 134.3, 132.4, 129.9, 128.0, 123.9, 123.1, 122.0, 108.5, 49.6, 46.2, 39.9, 29.4, 24.2, 21.13.7.1,
由实施例3制备得到的含有吲哚酮结构的硫酯化合物(I-3)的核磁共振(1H NMR和13C NMR)检测数据为：The nuclear magnetic resonance ( 1 H NMR and 13 C NMR) detection data of the thioester compound (I-3) containing the indolinone structure prepared in Example 3 is:
1H NMR(400MHz,CDCl3)δ7.27–7.24(m,1H),7.21–7.19(m,1H),7.03(td,J＝7.5,0.8Hz,1H),6.84(d,J＝7.8Hz,1H),3.33–3.27(m,1H),3.25(s,3H),3.16(d,J＝15.7Hz,1H),3.06(d,J＝15.7Hz,1H),1.75–1.54(m,4H),1.36(s,3H),1.33–1.15(m,6H). 1 H NMR (400MHz, CDCl 3 ) δ7.27–7.24(m,1H),7.21–7.19(m,1H),7.03(td,J=7.5,0.8Hz,1H),6.84(d,J=7.8 Hz, 1H), 3.33–3.27(m, 1H), 3.25(s, 3H), 3.16(d, J＝15.7Hz, 1H), 3.06(d, J＝15.7Hz, 1H), 1.75–1.54(m ,4H),1.36(s,3H),1.33–1.15(m,6H).
13C NMR(101MHz,CDCl3)δ195.0,179.6,143.4,132.3,128.0,122.7,122.2,108.1,50.4,46.2,42.2,32.8,32.6,26.4,25.71,25.70,25.4,24.1. 13 C NMR (101MHz, CDCl 3 ) δ195.0, 179.6, 143.4, 132.3, 128.0, 122.7, 122.2, 108.1, 50.4, 46.2, 42.2, 32.8, 32.6, 26.4, 25.71, 25.70, 25.4, 24.1.
由实施例4制备得到的含有吲哚酮结构的硫酯化合物(I-4)的核磁共振(1H NMR和13C NMR)检测数据为：The nuclear magnetic resonance ( 1 H NMR and 13 C NMR) detection data of the thioester compound (I-4) containing the indolinone structure prepared in Example 4 is:
1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.2Hz,1H),7.47(s,1H),7.13(d,J＝8.1Hz,2H),7.08(d,J＝8.2Hz,2H),6.87(d,J＝8.2Hz,1H),3.33(d,J＝16.4Hz,1H),3.27–3.23(m,4H),2.31(s,3H),1.41(s,3H). 1 H NMR (400MHz, CDCl 3 ) δ7.54(d, J=8.2Hz, 1H), 7.47(s, 1H), 7.13(d, J=8.1Hz, 2H), 7.08(d, J=8.2Hz ,2H),6.87(d,J=8.2Hz,1H),3.33(d,J=16.4Hz,1H),3.27–3.23(m,4H),2.31(s,3H),1.41(s,3H) .
13C NMR(101MHz,CDCl3)δ194.0,179.3,146.5,140.0,134.4,132.9,130.1,126.0(q,J＝3.9Hz),124.5(q,J＝32.4Hz),124.4(q,J＝271.5Hz),123.3,119.7(q,J＝3.5Hz),108.0,49.5,46.0,26.6,24.1,21.3. 13 C NMR (101MHz, CDCl 3 ) δ194.0, 179.3, 146.5, 140.0, 134.4, 132.9, 130.1, 126.0(q, J=3.9Hz), 124.5(q, J=32.4Hz), 124.4(q, J=271.5 Hz), 123.3, 119.7 (q, J=3.5Hz), 108.0, 49.5, 46.0, 26.6, 24.1, 21.3.
由实施例5制备得到的含有吲哚酮结构的硫酯化合物(I-5)的核磁共振(1H NMR和13C NMR)检测数据为：The nuclear magnetic resonance ( 1 H NMR and 13 C NMR) detection data of the thioester compound (I-5) containing the indolinone structure prepared in Example 5 is:
1H NMR(400MHz,CDCl3)δ7.18(dd,J＝8.2,5.3Hz,1H),7.13(d,J＝8.0Hz,2H),7.08(d,J＝8.2Hz,2H),6.71(ddd,J＝10.3,8.3,2.3Hz,1H),6.55(dd,J＝8.9,2.3Hz,1H),3.26(d,J＝16.1Hz,1H),3.21–3.17(m,4H),2.31(s,3H),1.38(s,3H). 1 H NMR (400MHz, CDCl 3 ) δ7.18(dd, J=8.2,5.3Hz,1H),7.13(d,J=8.0Hz,2H),7.08(d,J=8.2Hz,2H),6.71 (ddd, J=10.3,8.3,2.3Hz,1H),6.55(dd,J=8.9,2.3Hz,1H),3.26(d,J=16.1Hz,1H),3.21–3.17(m,4H), 2.31(s,3H),1.38(s,3H).
13C NMR(101MHz,CDCl3)δ193.9,179.6,163.0(d,J＝244.6Hz),144.9(d,J＝11.6Hz),139.8,134.3,130.0,127.4(d,J＝2.8Hz),123.7(d,J＝9.8Hz),123.5,108.2(d,J＝22.4Hz),97.1(d,J＝27.6Hz),49.7,45.7,26.5,24.1,21.2。 13 C NMR (101MHz, CDCl 3 ) δ193.9, 179.6, 163.0 (d, J = 244.6Hz), 144.9 (d, J = 11.6Hz), 139.8, 134.3, 130.0, 127.4 (d, J = 2.8Hz), 123.7 (d, J=9.8Hz), 123.5, 108.2 (d, J=22.4Hz), 97.1 (d, J=27.6Hz), 49.7, 45.7, 26.5, 24.1, 21.2.
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