CN105820137A - Novel method for synthesizing ortho diamido aromatic hydrocarbon through domino aryne precursor - Google Patents
Novel method for synthesizing ortho diamido aromatic hydrocarbon through domino aryne precursor Download PDFInfo
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- CN105820137A CN105820137A CN201610177424.4A CN201610177424A CN105820137A CN 105820137 A CN105820137 A CN 105820137A CN 201610177424 A CN201610177424 A CN 201610177424A CN 105820137 A CN105820137 A CN 105820137A
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- domino
- diamido
- ortho position
- aromatic hydrocarbon
- synthesis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/14—Thiadiazoles; Hydrogenated thiadiazoles condensed with carbocyclic rings or ring systems
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a novel method for synthesizing ortho diamido aromatic hydrocarbon through a domino aryne precursor. The synthesizing process comprises the steps that sulfonyl bridged diamine (such as alkylamine or arylamine), potassium carbonate and 18-crown-6 are mixed in a reaction solvent acetonitrile, the domino aryne precursor is slowly added at the temperature of 80 DEG C for a reaction for 8 h, and the ortho diamido aromatic hydrocarbon is efficiently prepared. The method for efficiently synthesizing the ortho diamido aromatic hydrocarbon through the domino aryne precursor has the advantages that reaction conditions are mild, no transition metal is needed, synthetic steps are short, and the yield is high. The method has the important value in the field of medicine synthesis and organic synthesis.
Description
Technical field
The present invention proposes a kind of new method utilizing the aminated aromatic hydrocarbons in domino aryne precursor synthesis ortho position two.
Background technology
Ortho position two amido aromatic hydrocarbons is a kind of important feature in machine compound, and this class formation is present in native compound, bioactive molecule, drug molecule, dyestuff and organic material in a large number.It is important research direction in synthetic organic chemistry by method realizes aromatic ring ortho position two aminated simply, efficiently.
The traditional preparation methods of the aminated aromatic hydrocarbons in ortho position two, it is generally required to experience multi-step chemical reaction and purification step, limits the extensive application of this compounds.Utilizing transition metal-catalyzed coupling reaction can realize the synthesis of these two amidos aromatic hydrocarbons, the synthesis for asymmetric product needs for multistep reaction, and meanwhile, the later stage of pharmaceutical synthesis generally requires to be avoided using transition metal.Therefore, seek one simply, efficiently synthetic method realize two and aminated have great importance.
This patent proposition is a kind of utilizes domino aryne precursor to react with the diamidogen of sulfonyl bridging, is prepared for the aminated aromatic hydrocarbons in ortho position two efficiently.Highly shortened synthesis step, turn avoid use transition metal simultaneously and participate in reaction.Additionally, this method is not only applicable to arylamine and the alkylamine of symmetry, and it is applicable to asymmetrical various diamidogen substrate.This meets requirement economic in pharmaceutical synthesis organic chemistry, efficient.
Summary of the invention
1, the main object of the present invention: in view of the aminated aromatic hydrocarbons in ortho position two is a kind of important molecular structure, traditional synthetic method complex steps, needs transition metal to participate in reaction.The present invention utilizes domino aryne precursor to react with the diamidogen of sulfonyl bridging, is prepared for the aminated aromatic hydrocarbons in ortho position two efficiently, by changing different bridged groups, has obtained the aromatic hydrocarbons that different two are aminated.This has important value in the drug molecule synthesis with native compound.
2, the principle of the present invention: the diamidogen designing sulfonyl bridging reacts with domino aryne as substrate; behind No. 1 position of first nucleophilic moiety attack aryne; No. 2 positions of the aryne that another nucleophilic moiety generates intramolecular attack second, obtain the aminated aromatic hydrocarbons in ortho position two.
Detailed description of the invention:
Below in conjunction with concrete reaction, further illustrate the present invention.As a example by sulfonyl bridging diphenylamines reacts with domino aryne.
First, by the diphenylamines substrate (50.0mg, 0.2mmol, 1.0equiv.) of sulfonyl bridging, K2CO3(110.4mg, 0.8mmol, 4.0equiv.), 18 crown ether six (211.4mg, 0.8mmol, 4.0equiv.) is dissolved in second cyanogen (10mL) reaction dissolvent, refluxes 30 minutes at 80 DEG C.
Secondly, then being slowly dropped in reaction solution through 8 hours at 80 DEG C by second cyanogen (10mL) solution of TPBT (268.0mg, 0.6mmol, 1.5equiv), mix homogeneously also reacts.
Finally, post processing: after reaction terminates, remove second cyanogen with Rotary Evaporators, obtain product ortho position two amido benzene through silica gel chromatography column separating purification, productivity is 85%.
Accompanying drawing explanation
Fig. 1 is diamidogen (in equation, R, R ＇ can be alkyl or aryl) and the aminated aromatic hydrocarbons in domino aryne precursor synthesis ortho position two that chemical equation describes sulfonyl bridging.
Fig. 2 is diphenylamines (when R, R ＇ is phenyl) and the domino aryne precursor synthesis ortho position two amido benzene that chemical equation describes sulfonyl bridging.
Compound property
Ortho position two amido benzene:
Mp:114-116℃；1HNMR(500MHz,CDCl3) δ 7.64 (d, J=7.5Hz, 4H), 7.57 (t, J=7.5Hz, 4H), 7.51 (t, J=7.5Hz, 2H), 6.98-6.94 (m, 2H), 6.72-6.68 (m, 2H) ppm；13CNMR(125MHz,CDCl3)δ132.6,130.4,130.3,129.8,128.6,122.3,109.5ppm；IR(thinfilm)1592,1484,1330,1301,1173,1155,947,738,691,568(cm-1)；HRMS-MALDI(m/z)calcdfor[C18H14NaN2O2S]+,345.0668；found,345.0673.
The medicine used
Claims (1)
1. the synthesis (as a example by the synthesis of ortho position two amido benzene) of the new method ortho position two amido aromatic hydrocarbons utilizing the aminated aromatic hydrocarbons in domino aryne precursor synthesis ortho position two,
It is characterized in that, specifically comprise the following steps that
Step one: by diphenylamines and the potassium carbonate (K of sulfonyl bridging2CO3), 18 crown ether six (18-c-6) mixing, add second cyanogen (MeCN) make solvent, under anhydrous, anaerobic conditions backflow 30 minutes.
Step 2: at keeping 80 DEG C, be slowly added to domino aryne precursor (TPBT) in 8 hours and react.
Step 3: remove second cyanogen with rotating additional issue instrument, obtained ortho position two amido benzene, be 85% through column chromatography purification yield.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610177424.4A CN105820137B (en) | 2016-03-25 | 2016-03-25 | A method of synthesizing two aminated aromatic hydrocarbons of ortho position using domino aryne precursor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610177424.4A CN105820137B (en) | 2016-03-25 | 2016-03-25 | A method of synthesizing two aminated aromatic hydrocarbons of ortho position using domino aryne precursor |
Publications (2)
| Publication Number | Publication Date |
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| CN105820137A true CN105820137A (en) | 2016-08-03 |
| CN105820137B CN105820137B (en) | 2018-10-30 |
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| CN201610177424.4A Expired - Fee Related CN105820137B (en) | 2016-03-25 | 2016-03-25 | A method of synthesizing two aminated aromatic hydrocarbons of ortho position using domino aryne precursor |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107935927A (en) * | 2017-12-01 | 2018-04-20 | 重庆大学 | A kind of synthesis of the more yuan of rings of benzo-aza |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104177395A (en) * | 2014-07-31 | 2014-12-03 | 重庆大学 | Benzyne precursor and synthesis method thereof |
| CN104829553A (en) * | 2015-03-16 | 2015-08-12 | 重庆大学 | New method of synthesizing 2,4-di-substituted benzothiazole |
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2016
- 2016-03-25 CN CN201610177424.4A patent/CN105820137B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104177395A (en) * | 2014-07-31 | 2014-12-03 | 重庆大学 | Benzyne precursor and synthesis method thereof |
| CN104829553A (en) * | 2015-03-16 | 2015-08-12 | 重庆大学 | New method of synthesizing 2,4-di-substituted benzothiazole |
Non-Patent Citations (1)
| Title |
|---|
| LU LI ET AL.: "Vicinal Diamination of Arenes with Domino Aryne Precursors", 《ORG. LETT.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107935927A (en) * | 2017-12-01 | 2018-04-20 | 重庆大学 | A kind of synthesis of the more yuan of rings of benzo-aza |
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| CN105820137B (en) | 2018-10-30 |
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