CN113292462A - Substituted allene thioether compound and preparation method thereof - Google Patents
Substituted allene thioether compound and preparation method thereof Download PDFInfo
- Publication number
- CN113292462A CN113292462A CN202110213423.1A CN202110213423A CN113292462A CN 113292462 A CN113292462 A CN 113292462A CN 202110213423 A CN202110213423 A CN 202110213423A CN 113292462 A CN113292462 A CN 113292462A
- Authority
- CN
- China
- Prior art keywords
- allene
- reaction
- producing
- compound according
- substituted allene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 allene thioether compound Chemical class 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 150000005676 cyclic carbonates Chemical class 0.000 claims abstract description 9
- 239000002585 base Substances 0.000 claims abstract description 8
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 5
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims abstract description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000001879 copper Chemical class 0.000 claims abstract description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 66
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 23
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 23
- 238000004440 column chromatography Methods 0.000 claims description 11
- 238000000746 purification Methods 0.000 claims description 11
- 238000000926 separation method Methods 0.000 claims description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 2
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- QVQGTNFYPJQJNM-UHFFFAOYSA-N dicyclohexylmethanamine Chemical compound C1CCCCC1C(N)C1CCCCC1 QVQGTNFYPJQJNM-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical group CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 2
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical group CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 19
- BTOWYENYYXRZMV-UHFFFAOYSA-N 2-methylidenethiirane Chemical compound C=C1CS1 BTOWYENYYXRZMV-UHFFFAOYSA-N 0.000 abstract description 8
- 239000002904 solvent Substances 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 15
- 239000000047 product Substances 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 238000001819 mass spectrum Methods 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- 238000001228 spectrum Methods 0.000 description 8
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001361 allenes Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 150000002596 lactones Chemical class 0.000 description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 2
- UIYCHXAGWOYNNA-UHFFFAOYSA-N vinyl sulfide Chemical compound C=CSC=C UIYCHXAGWOYNNA-UHFFFAOYSA-N 0.000 description 2
- PNAZUQUHTIOEHF-UHFFFAOYSA-N (3-methylphenyl)methanethiol Chemical compound CC1=CC=CC(CS)=C1 PNAZUQUHTIOEHF-UHFFFAOYSA-N 0.000 description 1
- GKQXPTHQTXCXEV-UHFFFAOYSA-N (4-chlorophenyl)methanethiol Chemical compound SCC1=CC=C(Cl)C=C1 GKQXPTHQTXCXEV-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- XMSFNEZQRPOHAR-UHFFFAOYSA-N 4-methylazetidin-2-one Chemical group CC1CC(=O)N1 XMSFNEZQRPOHAR-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/11—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/16—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/46—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms
- C07C323/49—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms to sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a substituted allene thioether compound and a preparation method thereof, belonging to the technical field of organic chemical synthesis, wherein the preparation method comprises the steps of dissolving a catalyst copper salt, alkali, acetylene base cyclic carbonate (II) or alkynyl carbamate lactone (III) and mercaptan/phenol (IV) in a reaction solvent, stirring for reaction at the temperature of 20-40 ℃, and separating and purifying after the reaction is finished to obtain the substituted allene thioether compound; the preparation method disclosed by the invention can be used for preparing a novel substituted allene sulfide compound, and the variety of functional organic synthetic building block allene sulfide is expanded; moreover, the preparation method has the advantages of novelty, simplicity in operation, mild reaction conditions, high selectivity, high yield and the like.
Description
Technical Field
The invention relates to the technical field of organic chemical synthesis, in particular to a substituted allene thioether compound and a preparation method thereof.
Background
Allenes and derivatives thereof are often used as important organic synthesis intermediates for the synthesis of structurally specific or pharmaceutically active molecules. Over the past few decades, a number of efficient methods have been developed for constructing various functional allenes.
Among these structurally diverse allenes, allene sulfide is widely used in the synthesis of complex compounds, and is a multifunctional organic synthetic block, as shown in fig. 1. For example, the synthesis of polysubstituted olefins from a bisalkenyl sulfide with nucleophiles such as halogens (e.g., iv in FIG. 1); the allene sulfide is also applied to the synthesis of thiazole, furan and pyran (such as v in figure 1); in addition, the allene thioether is also a precursor for synthesizing alpha-alkenyl beta-butyrolactam (such as vi in figure 1), and the alpha-alkenyl beta-lactam is a key structure of natural carbapenem antibiotics and is also an important synthetic intermediate thereof. Thus, the multifunctional substituted allene sulfides have a wide potential for use in the synthesis of complex compounds. The efficient synthesis of allene sulfides under simple and mild conditions remains a research area worth discussing and developing.
At present, the reaction of sulfide and alkynyl compound is one of the widely used methods for synthesizing allene sulfide. However, strong bases such as butyl lithium, potassium tert-butoxide and the like are commonly used in the reaction, the reaction needs low temperature and inert gas protection, and the operation is inconvenient; or the reaction selectivity is not high, and the products are accompanied by side products such as alkynyl sulfide (e.g. i in fig. 1), polymer (e.g. ii in fig. 1), sulfide oxide (e.g. iii in fig. 1) and the like besides the allene sulfide.
Therefore, it is an urgent need in the art to develop an effective method for synthesizing the allene sulfide to reduce the operation difficulty and improve the reaction selectivity.
Disclosure of Invention
One of the objectives of the present invention is to provide a substituted allene sulfide compound to solve the above problems.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows: the substituted allene thioether compound has a structure shown as the following formula (I):
wherein X is selected from hydroxyl, p-toluenesulfonamide or methanesulfonamide, R1Selected from H, halogen atoms or alkyl groups, R2Selected from alkyl or aryl.
The application value of the compound with novel structure provided by the invention is as follows: is a multifunctional organic synthesis intermediate, can be used for synthesizing polysubstituted olefin, aromatic heterocycle and natural product or medicine containing beta-butyrolactam structure skeleton.
The second purpose of the invention is to provide a preparation method of a substituted allene thioether compound, which adopts the technical scheme that: dissolving a catalyst, alkali, acetylene base cyclic carbonate (II) or alkynyl carbamate lactone (III) and mercaptan/phenol (IV) in a reaction solvent, stirring for reaction at 20-40 ℃, and separating and purifying after the reaction to obtain a product (I), wherein the product (I) is shown as follows:
wherein the catalyst is copper salt, and the reaction solvent is organic solvent.
As a preferred technical scheme: the copper salt is selected from one of copper acetate, copper trifluoromethanesulfonate, copper sulfate, copper tetraacetonitrile hexafluorophosphate, copper tetraacetonitrile tetrafluoroborate, cuprous chloride, cuprous bromide and cuprous iodide.
Among them, cuprous iodide is further preferably used as the catalyst because the yield is the highest.
As a preferred technical scheme: the alkali is at least one of triethylamine, diisopropylethylamine, dicyclohexylmethylamine, 4- (N, N-dimethylamino) pyridine, triethylene diamine and cesium carbonate.
Among them, diisopropylethylamine is further preferably used because the yield is highest.
As a preferred technical scheme: the organic solvent is at least one of dichloromethane, chloroform, tetrahydrofuran, acetonitrile, 1, 4-dioxane and ethyl acetate.
Among these, methylene chloride is more preferable.
As a preferred technical scheme: the amount of the catalyst used was 10 mol%.
As a preferred technical scheme: the amount of the base used was 1.0 equivalent.
As a preferred technical scheme: the minimum amount of the reaction solvent used is 0.5 mL per 0.1 mmol of the compound represented by the structural formula II or III.
As a preferred technical scheme: the separation and purification mode is column chromatography.
Compared with the prior art, the invention has the advantages that: the invention discloses a novel substituted allene sulfide compound for the first time, expands the variety of functional organic synthetic building block allene sulfide, and provides larger synthetic application space for the allene sulfide; the preparation method has the advantages of novelty, simplicity in operation, mild reaction conditions, high reaction selectivity, high yield and the like.
Drawings
FIG. 1 illustrates the side reactions of a common application and preparation method of a divinyl sulfide in the prior art;
FIG. 2 is a hydrogen spectrum of I-d obtained in example 4;
FIG. 3 is a carbon spectrum of I-d obtained in example 4;
FIG. 4 is a high resolution mass spectrum of I-d obtained in example 4.
Detailed Description
The invention will be further explained with reference to the drawings.
Example 1: synthesis of Compound (I-a)
To a dry reaction tube, cuprous iodide (0.02 mmol, 10 mol%), diisopropylethylamine (0.2 mmol, 1.0 eq.) solvent dichloromethane (1.0 mL, 0.2M) and 4-ethynyl-4-phenylcyclocarbonate (0.2 mmol, 1.0 eq.) were added in sequence, heated to 40 ℃, benzyl mercaptan (0.4 mmol, 2.0 eq.) was added dropwise, and stirred for 15 h. After the reaction was completed, the solvent was removed under reduced pressure, and column chromatography separation and purification (petroleum ether/ethyl acetate = 10/1) was carried out to obtain the product I-a as a white solid (48.0 mg, yield 90%).
The melting point, hydrogen spectrum, carbon spectrum and mass spectrum data of the obtained compound I-a are as follows:
m.p. 45.9-46.3 °C; 1H NMR (300 MHz, DMSO-d 6) δ 7.26 (m, 10H), 6.47 (s, 1H), 5.16 (t, J = 5.7 Hz, 1H), 4.41-4.25 (m, 2H), 3.92 (d, J = 13.3 Hz, 1H), 3.85 (d, J = 13.3 Hz, 1H); 13C NMR (151 MHz, DMSO-d 6 ) δ 200.9, 138.1, 134.6, 129.1, 128.7, 128.6, 127.5, 127.2, 126.6, 111.8, 91.6, 60.4, 36.1; HRMS (ESI) m/z: [M+Na]+ Calcd. for C17H16NaOS 291.0820; found: 291.0817.
example 2: synthesis of Compound (I-b)
To a dry reaction tube, cuprous iodide (0.02 mmol, 10 mol.), diisopropylethylamine (0.2 mmol, 1.0 eq.) solvent dichloromethane (1.0 mL, 0.2M) and 4-ethynyl-4- (3-methylphenyl) cyclic carbonate (0.2 mmol, 1.0 eq.) were added in sequence, heated to 40 deg.C, benzyl mercaptan (0.4 mmol, 2.0 eq.) was added dropwise, and stirred for 15 h. After the reaction was completed, the solvent was removed under reduced pressure, and column chromatography separation and purification (petroleum ether/ethyl acetate = 10/1) was carried out to obtain product I-b as a yellow oil 51.7 mg with a yield of 91%.
The hydrogen, carbon and mass spectra data of the obtained compound I-b are as follows:
1H NMR (300 MHz, DMSO-d 6) δ 7.34-7.15 (m, 6H), 7.11-7.00 (m, 3H), 6.46 (s, 1H), 5.14 (s, 1H), 4.39-4.22 (m, 2H), 3.92 (d, J = 13.3 Hz, 1H), 3.84 (d, J = 13.3 Hz, 1H), 2.25 (s, 3H); 13C NMR (101 MHz, DMSO-d 6) δ 200.4, 137.9, 137.4, 134.4, 128.9, 128.34, 128.3, 127.9, 127.0, 126.9, 123.6, 111.9, 91.3, 60.4, 35.8, 21.2;HRMS (ESI) m/z: [M+K]+ Calcd. for C18H18KOS 321.0710; found: 321.0706.
example 3: synthesis of Compound (I-c)
To a dry reaction tube, cuprous iodide (0.02 mmol, 10 mol.), diisopropylethylamine (0.2 mmol, 1.0 eq.) solvent dichloromethane (1.0 mL, 0.2M) and 4-ethynyl-4- (3-methylphenyl) cyclic carbonate (0.2 mmol, 1.0 eq.) were added in sequence, heated to 40 deg.C, benzyl mercaptan (0.4 mmol, 2.0 eq.) was added dropwise, and stirred for 15 h. After the reaction was completed, the solvent was removed under reduced pressure, and column chromatography separation and purification (petroleum ether/ethyl acetate = 10/1) was carried out to obtain 56.4 mg of a yellow oily substance as a product I-c in 99% yield.
The hydrogen, carbon and mass spectra data of the obtained compounds I-c are as follows:
1H NMR (300 MHz, DMSO-d 6) δ 7.35-7.25 (m, 5H), 7.25-7.10 (m, 4H), 6.36 (t, J = 2.2 Hz, 1H), 5.17 (br s, 1H), 4.35-4.21 (m, 2H), 3.93 (d, J = 13.2 Hz, 1H), 3.87 (d, J = 13.2 Hz, 1H); 13C NMR (151 MHz, DMSO-d 6) δ 201.3, 159.7 (d, J = 248.4 Hz), 137.7, 129.8 (d, J = 3.3 Hz), 129.3 (d, J = 8.5 Hz), 128.9, 128.4, 127.0, 124.4 (d, J = 3.5 Hz), 122.8 (d, J = 12.0 Hz), 115.9 (d, J = 22.0 Hz), 107.3, 90.2, 61.6, 35.8; HRMS (ESI) m/z: [M+K]+ Calcd. for C17H15FKOS 325.0465; found: 325.0476.
example 4: synthesis of Compound (I-d)
To a dry reaction tube, cuprous iodide (0.02 mmol, 10 mol.), diisopropylethylamine (0.2 mmol, 1.0 eq.) solvent, dichloromethane (1.0 mL, 0.2M) and 4-ethynyl-4-phenylcyclocarbonate (0.2 mmol, 1.0 eq.) were added in sequence, heated to 40 deg.C, 4-chlorobenzyl mercaptan (0.4 mmol, 2.0 eq.) was added dropwise, and stirred for 15 h. After the reaction was completed, the solvent was removed under reduced pressure, and column chromatography separation and purification (petroleum ether/ethyl acetate = 10/1) was carried out to obtain the product I-d as a white solid 52.0 mg with a yield of 86%.
The hydrogen spectrum (shown in FIG. 2), carbon spectrum (shown in FIG. 3) and high resolution mass spectrum (shown in FIG. 4) of the obtained compounds I-d were as follows:
m.p.97.6-97.8℃；1H NMR(300MHz,DMSO-d6)δ7.42-7.07(m,9H),6.46 (s,1H),5.19(t,J＝4.8Hz,1H),4.55-4.10(m,2H),3.92(d,J＝13.7Hz,1H),3.86 (d,J＝13.7Hz,1H)；13C NMR(101MHz,DMSO-d6)δ200.9,137.2,134.3,131.5, 130.7,128.3,128.26,127.2,126.4,111.6,91.0,60.3,35.0.HRMS(ESI)m/z: [M+Na]+Calcd.for C17H15ClNaOS 325.0424；found:325.0436。
example 5: synthesis of Compound (I-e)
To a dry reaction tube, cuprous iodide (0.02 mmol, 10 mol.), diisopropylethylamine (0.2 mmol, 1.0 eq.) solvent, dichloromethane (1.0 mL, 0.2M) and 4-ethynyl-4-phenylcyclocarbonate (0.2 mmol, 1.0 eq.) were added in sequence, heated to 40 deg.C, 3-methylbenzylthiol (0.4 mmol, 2.0 eq.) was added dropwise, and stirred for 15 h. After the reaction was completed, the solvent was removed under reduced pressure, and column chromatography separation and purification (petroleum ether/ethyl acetate = 10/1) was carried out to obtain the product I-e as a yellow oil 44.4 mg with a yield of 79%.
The hydrogen, carbon and mass spectra data of the obtained compounds I-e are as follows:
1H NMR (300 MHz, DMSO-d 6) δ 7.35- 7.17 (m, 5H), 7.16-7.05 (m, 3H), 7.02 (d, J = 6.4 Hz, 1H), 6.47 (s, 1H), 5.15 (t, J = 6.0 Hz, 1H), 4.34 (d, J= 5.6 Hz, 2H), 3.88 (d, J = 12.6 Hz, 1H), 3.80 (d, J = 13.2 Hz, 1H), 2.19 (s, 3H); 13C NMR (101 MHz, DMSO-d 6) δ 200.5, 137.8, 137.5, 134.4, 129.5, 128.4, 128.3, 127.6, 127.2, 126.4, 126.0, 111.7, 91.5, 60.4, 35.8, 20.9; HRMS (ESI) m/z: [M+Na]+ Calcd. for C18H18NaOS 305.0971; found: 305.0966.
example 6: synthesis of Compound (I-f)
To a dry reaction tube, cuprous iodide (0.02 mmol, 10 mol.), diisopropylethylamine (0.2 mmol, 1.0 eq.) solvent, dichloromethane (1.0 mL, 0.2M) and 4-ethynyl-4-phenyl-p-toluenesulfonylcarbamic acid lactone (0.2 mmol, 1.0 eq.) were added in that order, heated to 40 deg.C, benzyl mercaptan (0.4 mmol, 2.0 eq.) was added dropwise, and stirred for 15 h. After the reaction was completed, the solvent was removed under reduced pressure, and column chromatography separation and purification (petroleum ether/ethyl acetate = 10/1) was carried out to obtain the product I-f as a yellow solid 81.4 mg with a yield of 97%.
The melting point, hydrogen spectrum, carbon spectrum and mass spectrum data of the obtained compound I-f are as follows:
m.p. 48.9-49.7 oC; 1H NMR (300 MHz, DMSO-d 6) δ 7.92 (t, J = 6.1 Hz, 1H), 7.70 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H), 7.33-7.14 (m, 10H), 6.48 (s, 1H), 3.92 (d, J = 13.3 Hz, 1H), 3.83 (d, J = 13.3 Hz, 1H), 3.79-3.74 (m, 1H), 3.69 (dd, J = 12.6, 5.9 Hz, 1H), 2.38 (s, 3H); 13C NMR (101 MHz, DMSO-d 6) δ 201.0, 142.7, 137.6, 133.8, 129.61, 129.6, 128.8, 128.4, 128.3, 127.4, 127.0, 126.6, 126.2, 108.1, 92.7, 43.1, 35.6, 21.0; HRMS (ESI) m/z: [M+Na]+ Calcd. for C24H23NNaO2S2 444.1068; found: 444.1061.
example 7: synthesis of Compound (I-g)
To a dry reaction tube, cuprous iodide (0.02 mmol, 10 mol.), diisopropylethylamine (0.2 mmol, 1.0 eq.) and solvent dichloromethane (1.0 mL, 0.2M) and 4-ethynyl-4- (3-methyl) phenyl-p-toluenesulfonylcarbamic acid lactone (0.2 mmol, 1.0 eq.) were added in that order, heated to 40 deg.C, and benzylmercaptan IV (0.4 mmol, 2.0 eq.) was added dropwise and stirred for 15 h. After the reaction was completed, the solvent was removed under reduced pressure, and column chromatography separation and purification (petroleum ether/ethyl acetate = 10/1) was carried out to obtain product I-g, yellow oil 82.7 mg, yield 95%.
The hydrogen, carbon and mass spectra data of the obtained compounds I-g are as follows:
1H NMR (300 MHz, DMSO-d 6) δ 7.91 (t, J = 6.1 Hz, 1H), 7.71 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.31-7.26 (m, 2H), 7.25-7.13 (m, 4H), 7.07-6.95 (m, 3H), 6.45 (s, 1H), 3.92 (d, J = 13.4 Hz, 1H), 3.83 (d, J = 13.3 Hz, 1H), 3.80-3.75 (m, 1H), 3.70 (dd, J = 14.3, 5.6 Hz, 1H), 2.38 (s, 3H), 2.23 (s, 3H); 13C NMR (101 MHz, DMSO-d 6) δ 200.8, 142.7, 137.7, 137.6, 137.5, 133.8, 129.6, 128.8, 128.3, 128.2, 126.9, 126.86, 126.7, 123.4, 108.3, 92.6, 43.1, 35.5, 26.4, 21.1, 21.0; HRMS (ESI) m/z: [M+K]+ Calcd. for C25H25KNO2S2474.0964; found: 474.0962.
example 8: synthesis of Compound (I-h)
To a dry reaction tube, cuprous iodide (0.02 mmol, 10 mol.), diisopropylethylamine (0.2 mmol, 1.0 eq.) solvent, dichloromethane (1.0 mL, 0.2M) and 4-ethynyl-4-phenyl-methanesulfonyl carbamate lactone (0.2 mmol, 1.0 eq.) were added in that order, heated to 40 deg.C, benzylmercaptan IV (0.4 mmol, 2.0 eq.) was added dropwise and stirred for 15 h. After the reaction was completed, the solvent was removed under reduced pressure, and column chromatography separation and purification (petroleum ether/ethyl acetate = 10/1) was carried out to obtain product I-g, 62.0 mg of yellow oil, yield 90%.
The melting point, hydrogen, carbon and mass spectra data of the obtained compounds I-h are as follows:
m.p. 69.7-70.3 oC; 1H NMR (300 MHz, DMSO-d 6) δ 7.43-7.16 (m, 11H), 6.61 (s, 1H), 4.12-3.92 (m, 3H), 3.86 (d, J = 13.1 Hz, 1H), 2.93 (s, 3H); 13C NMR (101 MHz, DMSO-d 6) δ 200.6, 137.7, 134.0, 128.9, 128.5, 128.4, 127.5, 127.0, 126.3, 108.8, 93.3, 42.7, 39.9, 35.7; HRMS (ESI) m/z: [M+Na]+ Calcd. for C18H19NNaO2S2 368.0755; found: 368.0740.
example 9: synthesis of Compound (I-I)
To a dry reaction tube, cuprous iodide (0.02 mmol, 10 mol.), diisopropylethylamine (0.2 mmol, 1.0 eq.) solvent, dichloromethane (1.0 mL, 0.2M) and 4-ethynyl-4-phenyl-p-toluenesulfonylcarbamic acid lactone (0.2 mmol, 1.0 eq.) were added in that order, heated to 40 deg.C, 4-methylbenzylthiol IV (0.4 mmol, 2.0 eq.) was added dropwise and stirred for 15 h. After the reaction was completed, the solvent was removed under reduced pressure, and column chromatography separation and purification (petroleum ether/ethyl acetate = 10/1) was carried out to obtain product I-g, yellow oil 77.7 mg, yield 89%.
The hydrogen, carbon and mass spectra data of the obtained compounds I-I are as follows:
1H NMR (300 MHz, DMSO-d 6) δ 7.90 (t, J = 6.4 Hz, 1H), 7.69 (d, J = 8.2 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.32-7.22 (m, 3H), 7.22-7.13 (m, 4H), 7.03 (d, J = 7.8 Hz, 2H), 6.45 (s, 1H), 3.87 (d, J = 13.2 Hz, 1H), 3.84-3.63 (m, 3H), 2.39 (s, 3H), 2.24 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 200.9, 142.7, 137.6, 136.1, 134.4, 133.9, 129.6, 128.9, 128.8, 128.4, 127.4, 126.6, 126.3, 108.1, 92.8, 43.1, 35.3, 21.0, 20.7; HRMS (ESI) m/z: [M+Na]+ Calcd. for C25H25NNaO2S2 458.1219; found: 458.1198.
comparative examples 1 to 12
The following comparative examples were based on the above example 1, with different reaction conditions being changed, and the results are shown in Table 1 below.
TABLE 1 reaction conditions and results for different comparative examples
| Serial number | Catalyst (dosage) | Alkali (dosage) | Solvent (dosage) | Yield/%) |
| 1 | Cuprous iodide (10 mol%) | Diisopropylethylamine (1.0 eq) | Dichloromethane (1.0 mL) | 90 |
| 2 | Copper acetate (10 mol%) | Diisopropylethylamine (1.0 eq) | Dichloromethane (1.0 mL) | 82 |
| 3 | Trifluoromethanesulfonic acid ketone (10 mol%) | Diisopropylethylamine (1.0 eq) | Dichloromethane (1.0 mL) | 73 |
| 4 | Cuprous iodide (10 mol%) | Triethylene diamine (1.0 equivalent) | Dichloromethane (1.0 mL) | 83 |
| 5 | Cuprous iodide (10 mol%) | 4- (N, N-dimethyl) -pyridine (1.0 eq) | Dichloromethane (1.0 mL) | 53 |
| 6 | Cuprous iodide (10 mol%) | Cesium carbonate (1.0 eq) | Dichloromethane (1.0 mL) | 48 |
| 7 | Cuprous iodide (10 mol%) | Diisopropylethylamine (1.0 eq) | Toluene (1.0 mL) | 10 |
| 8 | Cuprous iodide (10 mol%) | Diisopropylethylamine (1.0 eq) | Acetonitrile (1.0 mL) | 19 |
| 9 | Cuprous iodide (10 mol%) | Diisopropylethylamine (1.0 eq) | Tetrahydrofuran (1.0 mL) | 65 |
| 10 | Cuprous iodide (5 mol%) | Diisopropylethylamine (1.0 eq) | Dichloromethane (1.0 mL) | 80 |
| 11 | Cuprous iodide (10 mol%) | Diisopropylethylamine (0.5 eq) | Dichloromethane (1.0 mL) | 88 |
| 12 | Cuprous iodide (10 mol%) | Diisopropylethylamine (1.0 eq) | Dichloromethane (2.0 mL) | 86 |
Note: reaction conditions in table 1: 0.2 mmol of 4-ethynyl-4-phenylcyclocarbonate, 0.4 mmol of benzylthiol, reaction time of 15 hours at 40 ℃ and isolated yield.
As can be seen from the above comparative examples, the catalyst used 10 mol% cuprous iodide, 1.0 equivalent diisopropylethylamine as a base, and 1.0 mL dichloromethane as a solvent under the same conditions gave the highest yield.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (9)
1. The substituted allene thioether compound is characterized in that: has the structure shown in the following formula (I):
wherein X is selected from hydroxyl, p-toluenesulfonamide or methanesulfonamide, R1Selected from H, halogen atoms or alkyl groups, R2Selected from alkyl or aryl.
2. The method for producing a substituted allene sulfide compound according to claim 1, wherein: dissolving a catalyst, alkali, acetylene base cyclic carbonate (II) or alkynyl carbamate lactone (III) and mercaptan/phenol (IV) in a reaction solvent, stirring for reaction at 20-40 ℃, and separating and purifying after the reaction to obtain a product (I), wherein the product (I) is shown as follows:
wherein the catalyst is copper salt, and the reaction solvent is organic solvent.
3. The method for producing a substituted allene sulfide compound according to claim 2, wherein: the copper salt is at least one selected from copper acetate, copper trifluoromethanesulfonate, copper sulfate, copper tetraacetonitrile hexafluorophosphate, copper tetraacetonitrile tetrafluoroborate, cuprous chloride, cuprous bromide and cuprous iodide.
4. The method for producing a substituted allene sulfide compound according to claim 2, wherein: the base is selected from triethylamine, diisopropylethylamine, dicyclohexylmethylamine, 4- (N-ethyl-N-methyl-4-methyl-ethyl-methyl-ethylN,N-dimethylamino) pyridine, triethylene diamine, cesium carbonate.
5. The method for producing a substituted allene sulfide compound according to claim 2, wherein: the organic solvent is at least one of dichloromethane, chloroform, tetrahydrofuran, acetonitrile, 1, 4-dioxane and ethyl acetate.
6. The method for producing a substituted allene sulfide compound according to claim 2, wherein: the amount of the catalyst used was 10 mol%.
7. The method for producing a substituted allene sulfide compound according to claim 2, wherein: the amount of the base used was 1.0 equivalent.
8. The method for producing a substituted allene sulfide compound according to claim 2, wherein: the reaction solvent was used in an amount of 0.5 mL per 0.1 mmol of the compound represented by the formula (II) or (III).
9. The method for producing a substituted allene sulfide compound according to claim 2, wherein: the separation and purification mode is column chromatography.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110213423.1A CN113292462B (en) | 2021-02-26 | 2021-02-26 | Substituted allene thioether compound and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110213423.1A CN113292462B (en) | 2021-02-26 | 2021-02-26 | Substituted allene thioether compound and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113292462A true CN113292462A (en) | 2021-08-24 |
| CN113292462B CN113292462B (en) | 2022-09-23 |
Family
ID=77319125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110213423.1A Expired - Fee Related CN113292462B (en) | 2021-02-26 | 2021-02-26 | Substituted allene thioether compound and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113292462B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20100078939A (en) * | 2008-12-30 | 2010-07-08 | 강원대학교산학협력단 | Novel allenyl sulfide compounds and synthesis of them |
-
2021
- 2021-02-26 CN CN202110213423.1A patent/CN113292462B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20100078939A (en) * | 2008-12-30 | 2010-07-08 | 강원대학교산학협력단 | Novel allenyl sulfide compounds and synthesis of them |
Non-Patent Citations (5)
| Title |
|---|
| GUO, K.ET AL: "Cu-Catalyzed Synthesis of Tetrasubstituted 2,3-Allenols through Decarboxylative Silylation of Alkyne-Substituted Cyclic Carbonates", 《ORG. LETT.》 * |
| KUN GUO ET AL: "Copper-Mediated Dichotomic Borylation of Alkyne Carbonates: Stereoselective Access to (E)-1,2-Diborylated 1,3-Dienes versus Traceless Monoborylation Affording a-Hydroxyallenes", 《ANGEW. CHEM. INT. ED.》 * |
| TAEKYU RYU ET AL: "Synthesis of Multisubstituted Allenes, Furans, and Pyrroles via Tandem Palladium-Catalyzed Substitution and Cycloisomerization", 《ORG. LETT.》 * |
| TANG, X.ET AL: "Synthesis of α-Hydroxyallenes by Copper-Catalyzed SN2′ Substitution of Propargylic Dioxolanones", 《EUR. J. ORG. CHEM.》 * |
| TOSHIAKI MURAI 等: "Synthesis and Properties of 1-Methylthiopropargylammonium Salts and Their Use as Key Precursors to Sulfur-Containing Enediynes", 《ORGANIC LETTERS》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113292462B (en) | 2022-09-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1826196B1 (en) | Vinyl ether compounds | |
| JP6396462B2 (en) | Mono- and dialkyl ethers of furan-2,5-dimethanol and (tetrahydrofuran-2,5-diyl) dimethanol and their amphiphilic derivatives | |
| JP2017504562A (en) | Furan-2,5-dimethanol and (tetrahydrofuran-2,5-diyl) dimethanol sulfonate and its derivatives | |
| CN108473454B (en) | A process for the preparation of formula (1) and intermediates therefor | |
| CN111978229B (en) | Synthesis method of dialkyl diselenide compound | |
| CN113292462B (en) | Substituted allene thioether compound and preparation method thereof | |
| CN111269156B (en) | Synthesis method of 1,2, 4-tricarbonyl sulfoxide ylide compound | |
| CN109535120B (en) | Preparation method of 7-substituted-3, 4,4, 7-tetrahydrocyclobutane coumarin-5-ketone | |
| CN113527173B (en) | Method for synthesizing indole terpene analogues through Heck tandem reaction | |
| CN110590621B (en) | Method for synthesizing 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne | |
| CN111793047B (en) | Preparation method of eribulin intermediate | |
| CN108947995B (en) | Preparation method of polysubstituted oxadiazine derivative | |
| CN108727323B (en) | Method for catalytically synthesizing trifluoromethyl substituted homoisoflavone compound by using N-heterocyclic carbene | |
| Li et al. | Silylative aromatization of p-quinone methides under metal and solvent free conditions | |
| CN115925673B (en) | Preparation method of six-membered ring monothiocarbonate | |
| CN114213298B (en) | Method for preparing thiosulfonate compound by directly oxidizing thiophenol | |
| CN112125843B (en) | Preparation method of 3-hydroxymethyl-4-phenyl-3, 4-dihydroquinolinone compound | |
| CN113620795B (en) | Method for synthesizing benzocycloheptenone compounds | |
| CN111018779A (en) | 2- (3-isoquinolyl) -ethyl propionate derivative and synthetic method thereof | |
| JP4635251B2 (en) | Organic bismuth compound and process for producing the same | |
| CN106905098B (en) | A kind of synthetic method of neighbour's iodo alpha-acyloxy carbonyls | |
| JP6659445B2 (en) | Debenzylation method | |
| CN105601597B (en) | A kind of method of the synthesizing tricyclic class compound of anion driving | |
| CN113845530A (en) | Convenient Michal addition reaction of 2-phenylbenzimidazole [2,1-b ] thiazole | |
| CN117603128A (en) | Preparation method of (3R, 6S) -3-amino-6-methylpiperidine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20220923 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |