CN114163385B - Method for promoting oxidation of tetrahydroisoquinoline compounds to lactam compounds by using surfactant - Google Patents
Method for promoting oxidation of tetrahydroisoquinoline compounds to lactam compounds by using surfactant Download PDFInfo
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- CN114163385B CN114163385B CN202111318078.4A CN202111318078A CN114163385B CN 114163385 B CN114163385 B CN 114163385B CN 202111318078 A CN202111318078 A CN 202111318078A CN 114163385 B CN114163385 B CN 114163385B
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- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
The invention relates to a method for promoting oxidation of tetrahydroisoquinoline compounds into lactam compounds by using a surfactant, belonging to the technical field of organic synthesis. The synthesis of lactam compounds is to take aryl substituted tetrahydroisoquinoline compounds on nitrogen as reaction substrates, pure water as solvent, oxygen as oxidant, and heat under the promotion of surfactant to react, thereby preparing the isoquinolinone compounds containing lactam fragments. The synthesis method of the invention does not need to adopt equivalent oxidant, ligand and alkali, does not need to adopt organic solvent, is green and environment-friendly, has simple synthesis steps, mild reaction conditions, simple and easy operation, high reaction yield up to 95 percent and wide applicable substrate range, provides a new way for converting tetrahydroisoquinoline compounds into corresponding lactam compounds, and has stronger industrial application prospect.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for promoting oxidation of tetrahydroisoquinoline compounds into lactam compounds by using a surfactant.
Background
Since amide bonds are commonly present in compounds having biological activity, such as peptides, proteins, penicillins, and the like, particularly lactam fragments, they are of interest as important components of antibacterial agents, antidiabetic agents, antibiotics, and drugs directed to the central nervous system. Furthermore, lactam fragments are also widely present in chemical raw materials, synthetic intermediates and agrochemicals. Therefore, the construction of amide bonds is a relatively important research direction in synthetic chemistry. And because of the important application of the lactam compound, the synthesis research of the isoquinolinone compound containing the lactam fragment is very necessary. Aiming at the synthesis method of isoquinoline ketone compounds containing lactam fragments, students at home and abroad have conducted extensive researches.
In 2012, the relaxation group of university of south Kokai was NaClO 2 Is an oxidizing agent in a mixed solvent (Cl 3 CMe/H 2 O=4:1) successfully oxidizes N-substituted tetrahydroisoquinoline derivatives to N-substituted 3, 4-dihydroisoquinolinones in reaction yields up to 94% (a.—r.song et al synthesis 2012,44,2903-2909).
In 2019, anna Lee group used Eosin Y as a photocatalyst under irradiation of blue light, K was used 2 CO 3 And NaN 3 At O 2 N-phenyl tetrahydroisoquinoline was successfully oxidized to N-phenyl-3, 4-dihydro-isoquinolone in an atmosphere, and the reaction was carried out in an organic solvent DMSO in a yield of up to 95% (A. Lee et al. Adv. Synth. Catalyst. 2019,361, 1124-1129).
In 2019, tsogaeva group of Ellangen-Nerenberg university uses Rose Bengal as a photocatalyst, and N-phenyl tetrahydroisoquinoline is oxidized into N-phenyl-3, 4-dihydroisoquinolinone by molecular oxygen oxidation under irradiation of green light using NaOAc as a base, and the reaction is similarly carried out in an organic solvent DMSO, and the yield reaches 72% (A.A. Guryev et al. Chem. Eur. J.2019,25, 4062-4066).
The above is about the synthesis of isoquinolinones containing lactam fragmentsIn the reports, it is often necessary to use environmentally unfriendly oxidizing agents, such as NaClO 2 Or requires an equivalent amount of base to promote the reaction, e.g. K 2 CO 3 ，NaN 3 NaOAc. In addition, the above reported synthetic methods generally employ organic solvents as the reaction medium. At present, few reports are made on synthesizing isoquinoline ketone compounds containing lactam fragments under the conditions of no environment-friendly oxidant, no equivalent base and no organic solvent. Therefore, the development of an environment-friendly synthesis method for synthesizing the isoquinolinone compound containing the lactam fragment has extremely important significance.
Disclosure of Invention
The invention aims to provide a method for promoting tetrahydroisoquinoline compounds to be oxidized into lactam compounds by using a surfactant, which is used for solving the technical problems that the existing synthesis method of isoquinoline ketone compounds containing lactam fragments often needs to adopt an oxidant which is not friendly to the environment, needs equivalent alkali and organic solvent, and does not meet the development requirements of green and environment protection.
A method for promoting the oxidation of tetrahydroisoquinoline compounds to lactam compounds by using a surfactant, wherein the reaction formula is as follows, and the method comprises the following steps:
step (1): taking an aryl substituted tetrahydroisoquinoline compound on nitrogen as a reaction substrate, dissolving a surfactant in pure water, then adding the reaction substrate, stirring and heating to react, wherein the reaction gas atmosphere is oxygen;
step (2): after the reaction is finished, the reaction system is restored to room temperature, an organic solvent is added to extract a crude product of the organic product, then the organic solvent is concentrated, and the obtained crude product of the organic product is separated and purified by column chromatography to obtain a final product.
Preferably, the aryl substituent is any one of aromatic hydrocarbon, heterocyclic aromatic hydrocarbon and polycyclic aromatic hydrocarbon.
Preferably, the amount of the surfactant is 5-10% of the mass fraction of the aryl-substituted tetrahydroisoquinoline compounds on nitrogen.
Preferably, the surfactant is any one of didodecyl dimethyl ammonium bromide, dioctadecyl dimethyl ammonium bromide and D-alpha-tocopheryl polyethylene glycol.
Preferably, the oxidant used in the reaction system is oxygen, the pressure of which is 0.1-0.5MPa.
Preferably, the reaction temperature in the step (1) is 60-110 ℃ and the reaction time is 4-24h.
The invention has the beneficial effects that: the method has the advantages of simple synthesis steps, mild reaction conditions, simple post-treatment, higher reaction yield, wide application range and stronger industrial application prospect compared with the traditional synthesis method, and the method has the advantages of environmental protection compared with the traditional synthesis method.
Drawings
FIG. 1 is N-phenyl-3, 4-dihydroisoquinolinone prepared in example 1 1 H NMR spectrum;
FIG. 2 is a diagram of N-phenyl-3, 4-dihydroisoquinolinone prepared in example 1 13 CNMR spectra.
Detailed Description
The following describes in detail the examples of the present invention, which are implemented on the premise of the technical solution of the present invention, and detailed embodiments and specific operation procedures are given, but the scope of protection of the present invention is not limited to the following examples.
A method for promoting the oxidation of tetrahydroisoquinoline compounds to lactam compounds by using a surfactant, which is characterized by comprising the following steps: the method comprises the following steps:
step (1): taking an aryl substituted tetrahydroisoquinoline compound on nitrogen as a reaction substrate, dissolving a surfactant in pure water, then adding the reaction substrate, stirring and heating to react, wherein the reaction gas atmosphere is oxygen;
step (2): after the reaction is finished, the reaction system is restored to room temperature, an organic solvent is added to extract a crude product of the organic product, then the organic solvent is concentrated, and the obtained crude product of the organic product is separated and purified by column chromatography to obtain a final product.
The aryl substituent is any one of aromatic hydrocarbon, heterocyclic aromatic hydrocarbon and polycyclic aromatic hydrocarbon.
The dosage of the surfactant is 5-10% of the mass fraction of the tetrahydroisoquinoline compound substituted by the aryl on nitrogen.
The surfactant is any one of didodecyl dimethyl ammonium bromide, dioctadecyl dimethyl ammonium bromide and D-alpha-tocopheryl polyethylene glycol.
The oxidant used in the reaction system is oxygen, and the pressure of the oxygen is 0.1-0.5MPa.
The reaction temperature in the step (1) is 60-110 ℃ and the reaction time is 4-24h.
Example 1
Preparation method of N-phenyl-3, 4-dihydro-isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 2.1mg (10 w.t.%) of didodecyl dimethyl ammonium bromide was dissolved in water, followed by 20.9mg (0.1 mmol) of the substrate N-phenyltetrahydroisoquinoline, and the mixture was added under 0.3MPa O 2 Stirring and reacting for 12h in an oil bath at 110 ℃ in a gas atmosphere, extracting the reaction liquid by using dichloromethane after the reaction is finished, and separating and purifying the crude product by column chromatography to obtain 21.2mg of target product. The product was found to have a structure of N-phenyl-3, 4-dihydroisoquinolinone by NMR and a yield of 95%. Target product characterization data: white solid. 1 H NMR(400MHz,CDCl 3 )δ8.19(dd,J＝7.7,1.1Hz,1H),7.53–7.33(m,6H),7.32–7.23(m,2H),4.07–3.90(m,2H),3.17(t,J＝6.4Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ164.25,143.13,138.34,132.08,129.73,128.95,128.77,127.23,126.99,126.29,125.36,49.45,28.65.MS(EI)m/z calcd for C 15 H 13 NO[M] + :223,found 223.
Example 2
Preparation method of N- (4-chloro-phenyl) -3, 4-dihydro-isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 2.4mg (10 w.t.%) of didodecyl dimethyl ammonium bromide was dissolved in water, followed by 24.3mg (0.1 mmol) of the substrate N- (4-chloro-phenyl) tetrahydroisoquinoline, and the mixture was added under 0.3MPa O 2 Stirring and reacting for 24 hours in an oil bath at 110 ℃ in a gas atmosphere, extracting a reaction liquid by using methylene dichloride after the reaction is finished, and separating and purifying a crude product by column chromatography to obtain 17.9mg of a target product, wherein the yield is 70%.
Example 3
Preparation method of N- (4-methoxy-phenyl) -3, 4-dihydro-isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 1.9mg (8 w.t.%) of dioctadecyl dimethyl ammonium bromide was dissolved in water, followed by 23.9mg (0.1 mmol) of the substrate N- (4-methoxy-phenyl) tetrahydroisoquinoline, at 0.2MPa O 2 Stirring and reacting for 8 hours in an oil bath at 90 ℃ in a gas atmosphere, extracting a reaction liquid by using methylene dichloride after the reaction is finished, and separating and purifying a crude product by column chromatography to obtain 18.2mg of a target product, wherein the yield is 72%.
Example 4
Preparation method of N-naphthyl-3, 4-dihydroisoquinolinone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 2.6mg (10 w.t.%) of didodecyl dimethyl ammonium bromide was dissolved in water, followed by 25.9mg (0.1 mmol) of the substrate N-naphthyl tetrahydroisoquinoline, and the mixture was added under 0.3MPa O 2 Stirring and reacting for 12h in an oil bath at 100 ℃ in a gas atmosphere, extracting the reaction liquid by using dichloromethane after the reaction is finished, and separating and purifying the crude product by column chromatography to obtain the target product 19.9mg, wherein the yield is 73%.
Example 5
Preparation method of N-pyridyl-3, 4-dihydro-isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 1.1mg (5 w.t.%) of D-alpha-tocopheryl polyethylene glycol was dissolved in water, followed by 21mg (0.1 mmol) of the substrate N-pyridyltetrahydroisoquinoline, at 0.3MPa O 2 Stirring and reacting for 24 hours in an oil bath at 60 ℃ in a gas atmosphere, extracting a reaction liquid by using methylene dichloride after the reaction is finished, and separating and purifying a crude product by column chromatography to obtain 13.4mg of a target product, wherein the yield is 60%.
Example 6
Preparation method of N-pyridyl-3, 4-dihydro isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 1.3mg (6w.t.%) of didodecyl dimethyl ammonium bromide was dissolved in water, followed by 21mg (0.1 mmol) of the substrate N-pyridyltetrahydroisoquinoline, and the mixture was added under 0.1MPa O 2 Stirring and reacting for 16h in an oil bath at 100 ℃ in a gas atmosphere, extracting the reaction liquid by using dichloromethane after the reaction is finished, and separating and purifying the crude product by column chromatography to obtain 14.6mg of a target product with the yield of 65%.
Example 7
Preparation method of N-pyridyl-3, 4-dihydro isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 1.5mg (7w.t.%) of dioctadecyl dimethyl ammonium bromide was dissolved in water, followed by 21mg (0.1 mmol) of the substrate N-pyridyltetrahydroisoquinoline, and the mixture was stirred under 0.5MPa O 2 Stirring and reacting for 4 hours in an oil bath at 90 ℃ in a gas atmosphere, extracting a reaction liquid by using methylene dichloride after the reaction is finished, and separating and purifying a crude product by column chromatography to obtain 15.2mg of a target product, wherein the yield is 68%.
The reaction results of synthesizing isoquinolinones containing lactam fragments under different reaction conditions are shown in Table 1:
TABLE 1
What has been described above is merely some embodiments of the present invention. It will be apparent to those skilled in the art that various modifications and improvements can be made without departing from the spirit of the invention.
Claims (2)
1. A method for promoting the oxidation of tetrahydroisoquinoline compounds to lactam compounds by using a surfactant, which is characterized by comprising the following steps: the method comprises the following steps:
step (1): taking an aryl substituted tetrahydroisoquinoline compound on nitrogen as a reaction substrate, dissolving a surfactant in pure water, then adding the reaction substrate, stirring and heating to react, wherein the reaction gas atmosphere is oxygen;
step (2): after the reaction is finished, the reaction system is restored to room temperature, an organic solvent is added to extract a crude product of the organic product, then the organic solvent is concentrated, and the obtained crude product of the organic product is separated and purified by column chromatography to obtain a final product;
ar is any one of phenyl, p-chlorophenyl, p-methoxyphenyl, 1-naphthyl and 1-pyridyl;
the dosage of the surfactant is 5-10% of the mass fraction of the tetrahydroisoquinoline compound substituted by the aryl on nitrogen;
the surfactant is any one of didodecyl dimethyl ammonium bromide, dioctadecyl dimethyl ammonium bromide and D-alpha-tocopheryl polyethylene glycol;
the pressure of the oxygen is 0.1-0.5MPa.
2. The method for promoting the oxidation of tetrahydroisoquinoline compounds to lactam compounds by using the surfactant according to claim 1, wherein the method comprises the following steps: the reaction temperature of the step (1) is 60-110 ℃ and the reaction time is 4-24h.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105153029A (en) * | 2015-08-27 | 2015-12-16 | 陕西师范大学 | Method for synthesizing isoquinoline ketone compounds |
| CN106588965A (en) * | 2015-10-15 | 2017-04-26 | 北京大学 | Urea peptidomimetic boric acid compound as well as pharmaceutical composition, preparation method and application thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105153029A (en) * | 2015-08-27 | 2015-12-16 | 陕西师范大学 | Method for synthesizing isoquinoline ketone compounds |
| CN106588965A (en) * | 2015-10-15 | 2017-04-26 | 北京大学 | Urea peptidomimetic boric acid compound as well as pharmaceutical composition, preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| Isoindolinone Synthesis: Selective Dioxane-Mediated Aerobic Oxidation of Isoindolines;Pawan Thapa，等;《The Journal of Organic Chemistry》;第84卷;第1025-1034页 * |
| Reaction of N-nitroaryl-1,2,3,4-tetrahydroisoquinoline derivatives with oxygen;Shawcross, A. P.，等;《Journal of Heterocyclic Chemistry》;第27卷(第2期);第367-369页 * |
| Thiyl radical promoted iron-catalyzed-selective oxidation of benzylic sp3 C–H bonds with molecular oxygen;Shasha Geng，等;《Chem. Commun.》;第55卷;第12699-12702页 * |
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