CN115746020A - Preparation of novel tetra-cyclic compounds without metal - Google Patents
Preparation of novel tetra-cyclic compounds without metal Download PDFInfo
- Publication number
- CN115746020A CN115746020A CN202211409378.8A CN202211409378A CN115746020A CN 115746020 A CN115746020 A CN 115746020A CN 202211409378 A CN202211409378 A CN 202211409378A CN 115746020 A CN115746020 A CN 115746020A
- Authority
- CN
- China
- Prior art keywords
- solvent
- reaction
- crude product
- preparation
- tetra
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 229910052751 metal Inorganic materials 0.000 title abstract description 5
- 239000002184 metal Substances 0.000 title abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 239000012043 crude product Substances 0.000 claims abstract description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 7
- 239000011630 iodine Substances 0.000 claims abstract description 7
- NVFIKNIKBITITJ-UHFFFAOYSA-N n-phenylmethoxybenzamide Chemical compound C=1C=CC=CC=1C(=O)NOCC1=CC=CC=C1 NVFIKNIKBITITJ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000010898 silica gel chromatography Methods 0.000 claims abstract description 4
- 238000003756 stirring Methods 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 238000001311 chemical methods and process Methods 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 4
- 238000001308 synthesis method Methods 0.000 abstract description 4
- 238000000746 purification Methods 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 238000004458 analytical method Methods 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000001923 cyclic compounds Chemical class 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 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 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 238000007832 transition metal-catalyzed coupling reaction Methods 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a preparation method of a novel tetra-heterocyclic compound without metal participation, belonging to the technical field of organic synthesis. The method comprises the following steps: to the reactor, N-benzyloxybenzamide and a higher valent iodine reagent were added. Stirring in a solvent, removing the solvent by using a rotary evaporator after the reaction is finished to obtain a crude product, and separating the crude product by silica gel column chromatography to obtain the target compound. The synthesis method of the novel tetra-heterocyclic compound provided by the invention has the characteristics of scientificity, reasonableness, simplicity in operation, high yield of the target compound, easiness in purification of the product and the like. The reaction equation is as follows:
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to preparation of a novel tetra-cyclic compound without participation of metal.
Background
The tetra-fused ring backbone is a very important occurrence, which is widely present in natural products and drug molecules. The traditional synthetic method usually needs multi-step reaction and treatment process, and development of a simple and efficient strategy is always concerned. In recent years, transition metal-catalyzed coupling reactions and hydrocarbon functionalization reactions have progressed rapidly and are being used effectively for the construction of four-fused-ring frameworks. Since the reaction involving the transition metal can cause metal residue in the final product, and the method cannot be applied to the industrial production of drug molecules, it is of great significance to develop an efficient metal-participation-free method for preparing the four-ring skeleton.
Disclosure of Invention
The purpose of the invention is as follows: to overcome the above-described deficiencies of the prior art, the present invention provides a method for preparing a novel tetranuclear compound by using a high-valent iodine reagent, as a supplement to the existing synthesis method of the tetranuclear compound.
The technical scheme is as follows: in order to achieve the purpose, the invention adopts the technical scheme that:
preparation of a novel metal-free tetra-cyclic compound having the structure shown in formula I:
R 1 the substituent is selected from phenyl, p-methylphenyl and p-methoxyphenyl, R 2 The substituent is selected from trifluoromethyl, R 3 The substituent is selected from methyl; the method is characterized in that N-benzyloxy benzamide and a high-valence iodine reagent are added into a reactor. Stirring in a solvent, removing the solvent by using a rotary evaporator after the reaction is finished to obtain a crude product, and separating the crude product by silica gel column chromatography to obtain the target compound. The chemical process is shown in a reaction formula II:
the molar ratio of the N-benzyloxy benzamide to the high-valence iodine reagent is 1: 1.1. The solvent is dichloromethane, the reaction temperature is room temperature, and the reaction time is 3 hours.
The invention has the beneficial effects that: the novel tetra-fused cyclic compound provided by the invention is scientific and reasonable in synthesis method, provides a new way for synthesizing the novel tetra-fused cyclic compound, obtains the novel tetra-fused cyclic compound with multiple substituents by the method, and is characterized by simple synthesis method, high yield of target products and easy purification of products.
Drawings
FIG. 1 is a chemical reaction scheme for the preparation of novel tetracyclic compounds;
FIG. 2 is an NMR spectrum of Compound 3a prepared in example 1;
FIG. 3 is an NMR spectrum of Compound 3b prepared in example 2;
FIG. 4 is an NMR spectrum of compound 3c prepared in example 3;
Detailed Description
The invention is described in further detail below with reference to the figures and specific examples.
The test methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials can be obtained from commercial sources or reported methods, unless otherwise specified.
Example 1
A5 mL reaction flask was charged with N-benzyloxybenzamide 1a (0.1mmol, 32.7mg), higher iodine reagent 2a (0.11mmol, 46.0mg) and methylene chloride (1 mL), and the mixture was stirred at room temperature for 3 hours. After the reaction was completed, the solvent was removed by using a rotary evaporator to obtain a crude product, and the crude product was separated by silica gel column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate = 1/1), and the solvent was removed by using a rotary evaporator to obtain the objective product 3a with a yield of 62%.
1 H NMR(600MHz，CDCl 3 )δ8.60(dd，J＝7.8，1.6Hz，1H)，7.58-7.50(m，5H)，7.33-7.29(m，2H)，7.27-7.21(m，3H)，6.95(ddd，J＝8.6，7.0，1.9Hz，1H)，6.80(d，J＝8.1Hz，1H)，5.27(s，2H). 13 C NMR(101MHz，CDCl 3 )δ156.6，136.4，136.3，135.2，132.1，131.7，131.4，129.4，129.4，128.7，128.2，127.8，127.4，127.1，126.2，126.0，125.8，124.7，116.4，73.3.
Example 2
The experimental results are shown in Table 1, except that 1b is used instead of 1a in example 1 and the conditions are the same as in example 1.
1 H NMR(600MHz，CDCl 3 )δ8.59(dd，J＝7.9，1.6Hz，1H)，7.57-7.49(m，2H)，7.31(d，J＝7.6Hz，2H)，7.28-7.20(m，3H)，7.17(d，J＝7.5Hz，2H)，6.97(td，J＝7.6，7.1，1.6Hz，1H)，6.87(d，J＝8.1Hz，1H)，5.26(s，2H)，2.48(s，3H). 13 C NMR(101MHz，CDCl 3 )δ156.6，138.0，136.5，135.2，133.3，132.0，131.7，131.2，130.2，129.5，128.6，127.7，127.4，127.0，126.3，126.0，125.8，124.7，116.4，73.3，21.4.
Example 3
The experimental results are shown in Table 1, except that 1c is used instead of 1a in example 1 and the conditions are the same as in example 1.
1 H NMR(400MHz，CDCl 3 )δ8.59(dd，J＝7.8，1.7Hz，1H)，7.59-7.49(m，2H)，7.30(d，J＝1.5Hz，1H)，7.26-7.19(m，4H)，7.06-6.98(m，3H)，6.88(d，J＝8.1Hz，1H)，5.26(s，2H)，3.92(s，3H). 13 C NMR(101MHz，CDCl 3 )δ159.4，156.6，136.6，135.1，132.5，132.0，131.8，129.4，128.6，128.3，127.7，127.4，127.0，126.4，126.0，125.8，124.7，116.0，114.8，112.3，73.2，55.3.
Example 4
The same conditions as in example 1 were used except that 1d was used instead of 1a in example 1, and the results of the experiment are shown in Table 1.
Spectrogram analysis data 3d
1 H NMR(600MHz，CDCl 3 )δ8.6(dd，J＝7.9，1.6Hz，1H)，7.6-7.5(m，1H)，7.5-7.5(m，4H)，7.3(t，J＝5.8Hz，3H)，7.1-7.0(m，2H)，6.5(s，1H)，5.2(s，2H)，2.0(s，3H). 13 C NMR(101MHz，CDCl 3 )δ156.7，136.9，136.5，136.2，132.3，132.0，131.9，131.4，130.3，129.4，129.3，128.1，127.7，127.0，125.9，125.9，125.8，124.4，116.2，73.2，21.2.
Example 5
The same conditions as in example 1 were used except that 1e was used instead of 1a in example 1, and the results of the experiment are shown in Table 1.
Spectrogram analysis data 3e
1 H NMR(600MHz，CDCl 3 )δ8.60(dd，J＝7.6，1.8Hz，1H)，7.61-7.52(m，5H)，7.49(d，J＝1.8Hz，1H)，7.32-7.28(m，2H)，7.26(dd，J＝7.8，1.5Hz，1H)，7.20(dd，J＝8.5，1.9Hz，1H)，6.90(d，J＝8.5 Hz，1H)，5.32(s，2H). 13 C NMR(101MHz，CDCl 3 )δ156.4，135.9，135.8，135.8，132.4，131.2，130.4，130.3，130.0，129.8，129.7，129.7，128.7，127.9，127.8，126.3，126.2，124.2(q，J＝3.6 Hz)，122.1，121.8(q，J＝3.6 Hz)，117.9，72.9. 19 F NMR(565MHz，CDCl 3 )δ-63.0.
TABLE 1
Claims (3)
1. Preparation of a novel metal-free tetra-cyclic compound having the structure shown in formula I:
R 1 the substituents are selected fromFrom phenyl, p-methylphenyl and p-methoxyphenyl, R 2 The substituent is selected from trifluoromethyl, R 3 The substituent is selected from methyl; the method is characterized in that N-benzyloxy benzamide and a high-valence iodine reagent are added into a reactor. Stirring in a solvent, removing the solvent by using a rotary evaporator after the reaction is finished to obtain a crude product, and separating the crude product by silica gel column chromatography to obtain the target compound. The chemical process is shown in a reaction formula II:
2. the method according to claim 1, wherein the molar ratio of the N-benzyloxybenzamide to the higher iodine reagent is 1: 1.1.
3. The method of claim 1, wherein: the solvent is dichloromethane, the reaction temperature is room temperature, and the reaction time is 3 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211409378.8A CN115746020A (en) | 2022-11-10 | 2022-11-10 | Preparation of novel tetra-cyclic compounds without metal |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211409378.8A CN115746020A (en) | 2022-11-10 | 2022-11-10 | Preparation of novel tetra-cyclic compounds without metal |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115746020A true CN115746020A (en) | 2023-03-07 |
Family
ID=85369324
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211409378.8A Pending CN115746020A (en) | 2022-11-10 | 2022-11-10 | Preparation of novel tetra-cyclic compounds without metal |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115746020A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS203756B1 (en) * | 1979-04-06 | 1981-03-31 | Bohumil Proksa | Tetracyclic compounds derived from narceonic acid and process for preparing thereof |
-
2022
- 2022-11-10 CN CN202211409378.8A patent/CN115746020A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS203756B1 (en) * | 1979-04-06 | 1981-03-31 | Bohumil Proksa | Tetracyclic compounds derived from narceonic acid and process for preparing thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109053661B (en) | Synthesis method of C-3 arylseleno substituted coumarin promoted by visible light | |
| CN113896674A (en) | Synthetic method of apremilast | |
| CN115746020A (en) | Preparation of novel tetra-cyclic compounds without metal | |
| CN110922369A (en) | Trifluoromethyl substituted dihydrofuran amine compound and preparation method and application thereof | |
| CN111848480A (en) | Method for synthesizing aryl difluoromethyl seleno ether from arylboronic acid and application thereof | |
| CN108947995B (en) | Preparation method of polysubstituted oxadiazine derivative | |
| CN110790708B (en) | Preparation method of Ailixipine intermediate | |
| CN108191736B (en) | 2, 3-disubstituted indole derivatives and preparation method thereof | |
| CN109851599B (en) | Preparation method of 2-aminobenzofuran compound | |
| CN109678862B (en) | Preparation method of polysubstituted distyryl indole derivative | |
| CN115785121A (en) | Preparation of novel spiro compounds catalyzed by high-valence iodine | |
| CN107445835B (en) | Synthesis method of 1, 2-dihydro cyclobuteno [ a ] naphthalene derivative and precursor thereof | |
| CN111471005A (en) | Indole-dihydronaphthalene compound and preparation method and application thereof | |
| CN112094234B (en) | Synthesis method of 6-phenyl-2, 3,4, 7-tetrahydro-1H-3-azepine derivative | |
| CN110078699B (en) | Synthesis method of C-3 thiocyanate substituted 4-amino coumarin derivative promoted by visible light | |
| CN115385835B (en) | Synthesis method of selenate compound | |
| CN111410656B (en) | Preparation method of isoquinolone derivative | |
| CN113480549B (en) | Imidazo [1,2-a ] pyrimidine compound and preparation method thereof | |
| CN114380743B (en) | Method for introducing trifluoromethylthio into nitrogen-containing compound | |
| CN114133389B (en) | Process for preparing isoindolin-1-one fused rings and analogues thereof | |
| CN114195820B (en) | Isoserine derivative, preparation thereof and application thereof in taxol synthesis | |
| CN104628644A (en) | 3-azabicyclo [4,1,0] heptyl aldehydes and preparation method thereof | |
| JP2002080415A (en) | Method for producing optically active 2,2'-binaphthol | |
| CN117263830A (en) | Method for synthesizing gamma-sulfonyl-alpha, alpha-difluoro aromatic compound | |
| CN117143066A (en) | Synthesis method of selenylbenzoxepin compound |
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 |