A method for synthesizing a nitrosated compound of a secondary amine
By reacting secondary amine compounds with nitro sources under the action of sulfonyl fluoride, the problem of using strong acids and oxidants in the existing nitrogen nitrosation methods is solved, and a single bond synthesis of nitrogen and nitrogen without oxidant is achieved, with a mild reaction Conditions and high yields, suitable for green chemical production.
Patent Information
- Application Number
- CN202310236843.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-03-13
- Publication Date
- 2024-12-10
- Estimated Expiration
- 2043-03-13
AI Technical Summary
The existing nitrogen nitrosation reaction methods have problems such as using strong acid media, difficult to deal with and store reagents, harsh reaction conditions, expensive oxidants and environmental pollution, which has led to the search for simple and safe nitrogen-nitrogen bonding methods becoming a research hotspot.
By mixing secondary amine compounds with nitro source, adding solvents and introducing sulfonyl fluorine for reaction, extraction, washing, drying, concentration and separation and purification, a nitrogen nitroscopic compound was prepared, avoiding the use of oxidizing agents, and magnetic stirring was used Treatment with silica gel column chromatography.
It realizes single-bonding synthesis of nitrogen and nitrogen under oxidant-free and mild reaction conditions, reduces environmental pollution, is simple to operate, has good functional compatibility and high yield, and meets the concept of green chemistry.
Smart Images
Figure CN116162040B_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing a nitrosated compound of a secondary amine. Background Art
[0002] Nitrogen-containing compounds are playing an increasingly important role in today's medicine, natural materials and other fields. Among them, nitrosamine compounds have attracted extensive attention and research due to their mature technology and unique biological and medicinal properties. Nitrosamine derivatives have carcinogenic, teratogenic and mutagenic characteristics, but these properties can be used to treat difficult and complicated diseases such as cancer. In addition, they play a very important role in the production and preparation of pesticides, providing raw materials for organic synthesis, the production and application of lubricant derivatives, and even vasodilation.
[0003] Nitrogen nitrosation is traditionally prepared by polar addition, using nitrous acid generated by sodium nitrite in water and inorganic acid to carry out nitrogen nitrosation. At the same time, a variety of different combination methods have been developed, such as: NaNO2-Phl(OAc)2, sodium nitrite-PTSA, sodium nitrite-alumina-methanesulfonic acid, etc. In addition, in the nitrogen nitrosation of secondary amines, the use of oxidants such as IBX / TBAF and Cu(OTf)2 / DBU / O2 has also received widespread attention and application.
[0004] According to literature reports, a lot of research has been done on the synthesis of nitrogen nitrosation reactions. However, most methods have limitations such as the use of strong acid media, difficult handling and storage of reagents, harsh reaction conditions, expensive oxidants, and environmental pollution. Therefore, finding a simpler and safer nitrogen-nitrogen bond synthesis method to synthesize nitrosamine compounds has always been one of the hot topics for chemists. Summary of the invention
[0005] The present invention is made to solve the above problems, and its purpose is to provide a method for synthesizing a nitrosated compound of a secondary amine.
[0006] The present invention provides a method for synthesizing a nitrosated compound of a secondary amine, which has the following characteristics and comprises the following steps:
[0007] Step S1, mixing the secondary amine compound and the nitro source uniformly, and then adding a solvent to obtain a mixed solution;
[0008] Step S2, introducing sulfonyl fluoride into the mixed solution for reaction, obtaining a reaction solution after the reaction is completed, extracting, washing, drying, concentrating, separating and purifying the reaction solution in sequence to obtain a nitrogen nitrosated compound,
[0009] Among them, the structural formula of the nitrogen nitrosated compound is: In the structural formula, R1 and R2 are one or more of an alkyl group, an aryl group, a substituted aryl group and a cyclic compound.
[0010] The method for synthesizing the nitrosated compound of a secondary amine provided by the present invention may also have the following characteristics: wherein the nitro source is a metal nitrite, and the molar ratio of the secondary amine compound to the metal nitrite is 1:1 to 1:100.
[0011] The method for synthesizing the nitrosated compound of a secondary amine provided by the present invention may also have the following characteristics: wherein the solvent is a mixed solvent of an organic substance and water, the volume ratio of the organic solvent to water is 1:1 to 100:1, and the total volume of the solvent is 1 ml to 1000 ml.
[0012] The method for synthesizing the nitrosated compound of a secondary amine provided by the present invention may also have the following characteristics: wherein, in step S2, when sulfonyl fluoride is introduced into the mixed solution for reaction, magnetic stirring is performed, and the reaction temperature is 0° C. to 100° C., and the reaction time is 1 h to 24 h.
[0013] The method for synthesizing the nitrosated compound of a secondary amine provided by the present invention may also have the following characteristics: wherein, in step S2, when performing extraction, the extractant is ethyl acetate, the volume of the extractant is 30 ml, and the number of extractions is 3 times.
[0014] The method for synthesizing the nitrosated compound of a secondary amine provided by the present invention may also have the following characteristics: wherein, in step S2, when washing is performed, the washing agent is a saturated sodium chloride solution, and when drying is performed, the drying agent is anhydrous sodium sulfate.
[0015] The method for synthesizing the nitrosated compound of a secondary amine provided by the present invention may also have the following feature: wherein, in step S2, the concentration is reduced-pressure concentration.
[0016] The method for synthesizing the nitrosated compound of a secondary amine provided by the present invention may also have the following characteristics: wherein, in step S2, silica gel column chromatography is used for separation and purification, the silica gel mesh number used in the silica gel column chromatography is 100 mesh to 400 mesh, the eluent is ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate to petroleum ether is 1:10 to 1:50.
[0017] Functions and Effects of the Invention
[0018] According to the synthesis method of a nitrosated compound of a secondary amine involved in the present invention, after the secondary amine compound and the nitro source are evenly mixed, a reaction solvent is added, and then sulfonyl fluoride is introduced into the reaction system to carry out a chemical reaction to prepare a nitrogen nitrosated compound. The present invention realizes a new nitrogen-nitrogen single bond synthesis method to synthesize nitrosamine compounds, and compared with the traditional synthesis method, the synthesis method of the present invention does not need to use an oxidant or a catalyst, reduces pollution to the environment, and is simple to operate, mild reaction conditions, good substrate universality, and has good functional compatibility. At the same time, cheap and easily available sulfonyl fluoride is used as a reaction promoter, which has lower cost and higher yield, and can better meet the concept of green production and green chemistry. BRIEF DESCRIPTION OF THE DRAWINGS
[0019] Figure 1 This is a physical diagram of a reaction device used in a method for synthesizing a nitrosated compound of a secondary amine in an embodiment of the present invention;
[0020] Figure 2 This is the reaction route of the nitrosated compound of the secondary amine in Example 1 of the present invention;
[0021] Figure 3 is the N-methyl-N-nitrosobenzylamine compound in Example 1 of the present invention 1 H NMR spectra;
[0022] Figure 4 is the N-methyl-N-nitrosobenzylamine compound in Example 1 of the present invention 13 C NMR spectra;
[0023] Figure 5 is the N-allyl-N-nitrosobenzylamine compound in Example 2 of the present invention 1 H NMR spectra;
[0024] Figure 6 is the N-allyl-N-nitrosobenzylamine compound in Example 2 of the present invention 13 C NMR spectra;
[0025] Figure 7 is the N-methyl-N-nitroso-p-methoxybenzylamine compound in Example 3 of the present invention 1 H NMR spectra;
[0026] Figure 8 is the N-methyl-N-nitroso-p-methoxybenzylamine compound in Example 3 of the present invention 13 C NMR spectra;
[0027] Fig. 9 is the N-methyl-N-nitroso-p-chlorobenzylamine compound in Example 4 of the present invention 1HNMR spectra;
[0028] Fig.10 is the N-methyl-N-nitroso-p-chlorobenzylamine compound in Example 4 of the present invention 13 CNMR images;
[0029] Fig.11 is the N-nitrosoiminodiacetonitrile compound in Example 5 of the present invention 1 H NMR spectra;
[0030] Fig.12 is the N-nitrosoiminodiacetonitrile compound in Example 5 of the present invention 13 C NMR spectrum. DETAILED DESCRIPTION
[0031] A method for synthesizing a nitrosated compound of a secondary amine of the present invention comprises the following steps:
[0032] Step S1, mixing the secondary amine compound and the nitro source evenly, and then adding a solvent to obtain a mixed solution.
[0033] The nitro source is a metal nitrite, including sodium nitrite, potassium nitrite and the like, and the molar ratio of the secondary amine compound to the metal nitrite is 1:1 to 1:100.
[0034] The solvent is a mixed solvent of organic matter and water, the volume ratio of the organic solvent to water is 1:1 to 100:1, and the total volume of the solvent is 1 ml to 1000 ml.
[0035] Step S2, introducing sulfonyl fluoride into the mixed solution for reaction, obtaining a reaction solution after the reaction is completed, and extracting, washing, drying, concentrating, separating and purifying the reaction solution in sequence to obtain a nitrogen nitrosated compound.
[0036] In step S2, sulfonyl fluoride is used as a reaction accelerator. When sulfonyl fluoride is introduced into the mixed solution for reaction, magnetic stirring is performed, and the reaction temperature is 0° C. to 100° C., and the reaction time is 1 h to 24 h.
[0037] In step S2, when the extraction is performed, the extractant is ethyl acetate, the volume of the extractant is 30 ml, and the number of extractions is 3 times.
[0038] In step S2, when the washing is performed, the detergent is a saturated sodium chloride solution, and when the drying is performed, the desiccant is anhydrous sodium sulfate.
[0039] In step S2, the concentration is concentration under reduced pressure.
[0040] In step S2, silica gel column chromatography is used for separation and purification. The silica gel mesh used in the silica gel column chromatography is 100-400 mesh, and the eluent is ethyl acetate and petroleum ether. The volume ratio of ethyl acetate to petroleum ether is 1:10-1:50.
[0041] The structural formula of nitrogen nitrosated compounds is: In the structural formula, R1 and R2 are one or more of an alkyl group, an aryl group, a substituted aryl group and a cyclic compound.
[0042] In the present invention, in the corresponding substituted aromatic group, the substituent groups include: methyl, methoxy, halogen, nitro and other electron-donating groups or electron-withdrawing groups, and also include different positions of different substituents, and carbon atoms on the aromatic group are replaced by different heteroatoms. At the same time, the cyclic compound also involves different sizes of the cyclic compound, and a wide variety of functional groups on the cyclic compound and different substitution positions of the functional groups.
[0043] In order to make the technical means, creative features, objectives and effects of the present invention easier to understand, the following examples are combined with the accompanying drawings to specifically describe the synthesis method of the nitrosated secondary amine compound of the present invention.
[0044] Figure 1 This is a physical diagram of a reaction device used in a method for synthesizing a nitrosated compound of a secondary amine in an embodiment of the present invention.
[0045] like Figure 1 As shown, in the embodiments of the present invention, a three-necked flask is used as a reaction container, a magnetic stirrer and a constant temperature magnetic stirrer are used to perform magnetic stirring, a balloon is selected as a gas storage tool to store sulfonyl fluoride, and a long needle is used to introduce the mixed solution of the three-necked flask in the form of bubbling.
[0046] <Example 1>
[0047] The synthesis method of a nitrosated compound of a secondary amine of the present embodiment comprises the following steps:
[0048] Step S1, prepare a 25ml three-necked flask required for the reaction, add a magnetic stirrer into the flask, add weighed N-methylbenzylamine (2mmol) and nitrite (10mmol) in sequence and mix well, then add a solvent with a syringe, the solvent is a mixed solvent of organic matter (8ml) and water (2ml), to obtain a mixed solution.
[0049] Step S2, using a balloon as a gas storage tool, collecting sulfonyl fluoride from a gas cylinder, using a long needle (diameter = 0.9 mm) to introduce it into the mixed solution in the form of bubbling, then putting it into a constant temperature magnetic stirrer, magnetically stirring it at room temperature, reacting for 2 hours, tracking the reaction progress according to TLC, and obtaining a reaction solution after the reaction is completed. The reaction solution is extracted three times with ethyl acetate (30 ml) and water, and the organic phase is collected. The inorganic salt is removed with saturated sodium chloride, and then dried with anhydrous Na2SO4, and the solvent is removed by concentration under reduced pressure. Finally, the pure target product N-methyl-N-nitrosobenzylamine compound is obtained by silica gel column chromatography.
[0050] Figure 2 This is the reaction route of the nitrosated compound of the secondary amine in Example 1 of the present invention.
[0051] like Figure 2 As shown, in this embodiment, the secondary amine compound is N-methylbenzylamine, and the product prepared under the reaction conditions of nitrite and sulfonyl fluoride is N-methyl-N-nitrosobenzylamine compound.
[0052] Figure 3 is the N-methyl-N-nitrosobenzylamine compound in Example 1 of the present invention 1 HNMR spectra; Figure 4 is the N-methyl-N-nitrosobenzylamine compound in Example 1 of the present invention 13 C NMR spectrum.
[0053] like Figure 3 and Figure 4 As shown, the spectrum analysis results of the finished product prepared in this embodiment are as follows: 1H NMR (400MHz, Chloroform-d) δ7.54-6.82 (m, 5H), 5.26 (s, 2H), 4.76 (s, 1H), 3.64 (s, 1H), 2.89 (d, J = 0.8Hz, 3H). 13C NMR (101MHz, Chloroform-d) δ134.57, 133.85, 129.01, 128.85, 128.49, 128.30, 128.03, 127.89, 57.45, 47.69, 38.36, 30.83. This embodiment successfully prepared N-methyl-N-nitrosobenzylamine compound, and the structural formula of N-methyl-N-nitrosobenzylamine compound is as follows:
[0054]
[0055] In this embodiment, N-methylbenzylamine is the raw material for preparation, and N-methyl-N-nitrosobenzylamine compound is the product for preparation, and the calculated yield is 83%.
[0056] <Example 2>
[0057] The synthesis method of a nitrosated compound of a secondary amine of the present embodiment comprises the following steps:
[0058] Step S1, prepare a 25 ml three-necked flask required for the reaction, add a magnetic stirrer into the flask, add weighed N-allylbenzylamine (2 mmol) and nitrite (10 mmol) in sequence and mix well, then add a solvent with a syringe, the solvent is a mixed solvent of organic matter (8 ml) and water (2 ml), to obtain a mixed solution.
[0059] Step S2, using a balloon as a gas storage tool, collecting sulfonyl fluoride from a gas cylinder, using a long needle (diameter = 0.9 mm) to introduce it into the mixed solution in the form of bubbling, then putting it into a constant temperature magnetic stirrer, magnetically stirring it at room temperature, reacting for 2 hours, tracking the reaction progress according to TLC, and obtaining a reaction solution after the reaction is completed. The reaction solution is extracted three times with ethyl acetate (30 ml) and water, and the organic phase is collected. The inorganic salt is removed with saturated sodium chloride, and then dried with anhydrous Na2SO4, and the solvent is removed by concentration under reduced pressure. Finally, the pure target product N-allyl-N-nitrosobenzylamine compound is obtained by silica gel column chromatography.
[0060] Figure 5 is the N-allyl-N-nitrosobenzylamine compound in Example 2 of the present invention 1 HNMR spectra; Figure 6 is the N-allyl-N-nitrosobenzylamine compound in Example 2 of the present invention 13 C NMR spectrum.
[0061] like Figure 5 and Figure 6As shown, the spectrum analysis results of the finished product prepared in this example are as follows: 1H NMR(400MHz,Chloroform-d)δ7.46–7.32(m,2H),7.32–7.24(m,3H),7.19–7.0 0(m,1H),5.88(ddt,J=16.6,10.2,6.2Hz,1H),5.55(ddt,J=16.4,10.2,6.1Hz, 1H),5.38–5.22(m,3H),5.15(dq,J=10.2,1.3Hz,1H),5.03(dq,J=17.1,1.4Hz, 1H),4.78(s,1H),4.66(dt,J=6.3,1.4Hz,1H),4.07(dt,J=6.1,1.4Hz,2H).13C NMR (101MHz, Chloroform-d) δ134.67, 134.05, 131.81, 129.21, 128.97, 128.78, 128.49, 128.35, 128.29, 127.81, 120.29, 119.23, 55.20, 53.91, 45.32, 44.89. This example successfully prepared an N-allyl-N-nitrosobenzylamine compound. The structural formula of the N-allyl-N-nitrosobenzylamine compound is as follows:
[0062]
[0063] In this example, N-allyl benzylamine is the raw material, and N-allyl-N-nitrosobenzylamine compound is the product, and the calculated yield is 94%.
[0064] <Example 3>
[0065] The synthesis method of a nitrosated compound of a secondary amine of the present embodiment comprises the following steps:
[0066] Step S1, prepare a 25 ml three-necked flask required for the reaction, add a magnetic stirrer into the flask, add weighed N-(4-methoxybenzyl)-N-methylamine (2 mmol) and nitrite (10 mmol) in sequence and mix well, then add a solvent with a syringe, the solvent is a mixed solvent of organic matter (8 ml) and water (2 ml), to obtain a mixed solution.
[0067] Step S2, using a balloon as a gas storage tool, collecting sulfonyl fluoride from a gas cylinder, using a long needle (diameter = 0.9 mm) to introduce it into the mixed solution in the form of bubbling, then putting it into a constant temperature magnetic stirrer, magnetically stirring it at room temperature, reacting for 2 hours, tracking the reaction progress according to TLC, and obtaining a reaction solution after the reaction is completed. The reaction solution is extracted three times with ethyl acetate (30 ml) and water, and the organic phase is collected. The inorganic salt is removed with saturated sodium chloride, and then dried with anhydrous Na2SO4, and the solvent is removed by vacuum concentration. Finally, the pure target product N-methyl-N-nitroso-p-methoxybenzylamine compound is obtained by silica gel column chromatography.
[0068] Figure 7 is the N-methyl-N-nitroso-p-methoxybenzylamine compound in Example 3 of the present invention 1 H NMR spectra; Figure 8 is the N-methyl-N-nitroso-p-methoxybenzylamine compound in Example 3 of the present invention 13 C NMR spectrum.
[0069] like Figure 7 and Figure 8 As shown, the spectrum analysis results of the finished product prepared in this example are as follows: 1H NMR (400MHz, Chloroform-d) δ7.23-7.15 (m, 2H), 6.94-6.86 (m, 2H), 5.23 (s, 2H), 3.79 (d, J = 8.4 Hz, 3H), 3.65 (s, 1H), 2.91 (s, 2H). 13C NMR (101MHz, Chloroform-d) δ159.76, 129.62 (d, J = 38.0Hz), 126.35, 125.88, 114.27 (d, J = 17.6Hz), 77.48, 56.91, 55.21 (d, J = 4.5Hz), 47.11, 38.17, 30.60. In this example, N-methyl-N-nitroso-p-methoxybenzylamine was successfully prepared. The structural formula of N-methyl-N-nitroso-p-methoxybenzylamine is as follows:
[0070]
[0071] In this example, N-(4-methoxybenzyl)-N-methylamine is the raw material, and N-methyl-N-nitroso-p-methoxybenzylamine is the product, with a yield of 77%.
[0072] <Example 4>
[0073] The synthesis method of a nitrosated compound of a secondary amine of the present embodiment comprises the following steps:
[0074] Step S1, prepare a 25ml three-necked flask required for the reaction, add a magnetic stirrer into the flask, add weighed 1-(4-chlorophenyl)-N-methylmethylamine (2mmol) and nitrite (10mmol) in sequence and mix well, then add a solvent with a syringe, the solvent is a mixed solvent of organic matter (8ml) and water (2ml), to obtain a mixed solution.
[0075] Step S2, using a balloon as a gas storage tool, collecting sulfonyl fluoride from a gas cylinder, using a long needle (diameter = 0.9 mm) to introduce it into the mixed solution in the form of bubbling, then putting it into a constant temperature magnetic stirrer, magnetically stirring it at room temperature, reacting for 2 hours, tracking the reaction progress according to TLC, and obtaining a reaction solution after the reaction is completed. The reaction solution is extracted three times with ethyl acetate (30 ml) and water, and the organic phase is collected. The inorganic salt is removed with saturated sodium chloride, and then dried with anhydrous Na2SO4, and the solvent is removed by concentration under reduced pressure. Finally, the pure target product N-methyl-N-nitroso-p-chlorobenzylamine compound is obtained by silica gel column chromatography.
[0076] Fig. 9 is the N-methyl-N-nitroso-p-chlorobenzylamine compound in Example 4 of the present invention 1 H NMR spectra; Fig.10 is the N-methyl-N-nitroso-p-chlorobenzylamine compound in Example 4 of the present invention 13 C NMR spectrum.
[0077] like Fig. 9 and Fig.10 As shown, the spectrum analysis results of the finished product prepared in this example are as follows: 1H NMR (400MHz, Chloroform-d) δ7.37-7.30 (m, 1H), 7.30-7.22 (m, 1H), 7.19 (d, J = 8.5Hz, 1H), 7.08-7.01 (m, 1H), 5.26 (s, 1H), 4.74 (s, 1H), 3.68 (s, 1H), 2.91 (s, 2H). 13C NMR (101MHz, Chloroform-d) δ134.41, 133.73, 133.16, 132.41, 129.68, 129.42, 129.19, 128.97, 56.72, 47.06, 38.42, 30.84. This example successfully prepared N-methyl-N-nitroso-p-chlorobenzylamine compound. The structural formula of the N-methyl-N-nitroso-p-chlorobenzylamine compound is as follows:
[0078]
[0079] In this embodiment, 1-(4-chlorophenyl)-N-methylmethylamine is the raw material, and N-methyl-N-nitroso-p-chlorobenzylamine compound is the product, and the calculated yield is 74%.
[0080] <Example 5>
[0081] The synthesis method of a nitrosated compound of a secondary amine of the present embodiment comprises the following steps:
[0082] Step S1, prepare a 25ml three-necked flask required for the reaction, add a magnetic stirrer into the flask, add weighed iminodiacetonitrile (2mmol) and nitrite (10mmol) in sequence and mix well, then add a solvent with a syringe, the solvent is a mixed solvent of organic matter (8ml) and water (2ml), to obtain a mixed solution.
[0083] Step S2, using a balloon as a gas storage tool, collecting sulfonyl fluoride from a gas cylinder, using a long needle (diameter = 0.9 mm) to introduce it into the mixed solution in the form of bubbling, then putting it into a constant temperature magnetic stirrer, magnetically stirring it at room temperature, reacting for 2 hours, tracking the reaction progress according to TLC, and obtaining a reaction solution after the reaction is completed. The reaction solution is extracted three times with ethyl acetate (30 ml) and water, and the organic phase is collected. The inorganic salt is removed with saturated sodium chloride, and then dried with anhydrous Na2SO4, and then concentrated under reduced pressure to remove the solvent. Finally, the pure target product N-nitrosoiminodiacetonitrile is obtained by silica gel column chromatography.
[0084] Fig.11 is the N-nitrosoiminodiacetonitrile compound in Example 5 of the present invention 1 HNMR spectra; Fig.12 is the N-nitrosoiminodiacetonitrile compound in Example 5 of the present invention 13 C NMR spectrum.
[0085] like Fig.11 and Fig.12 As shown, the spectrum analysis results of the finished product prepared in this embodiment are as follows: 1H NMR (400MHz, DMSO-d6) δ5.62 (d, J = 0.8Hz, 1H), 4.78 (d, J = 0.8Hz, 1H). 13C NMR (101MHz, DMSO-d6) δ115.22, 113.37, 40.71, 40.02, 32.50. This embodiment successfully prepared an N-nitrosoiminodiacetonitrile compound, and the structural formula of the N-nitrosoiminodiacetonitrile compound is as follows:
[0086]
[0087] In this embodiment, iminodiacetonitrile is the preparation raw material, N-nitrosoiminodiacetonitrile is the preparation product, and the calculated yield is 88%.
[0088] Functions and Effects of the Embodiments
[0089] According to Example 1-Example 5, a method for synthesizing a nitrosated compound of a secondary amine of the present invention is to mix a secondary amine compound with a nitro source, add a reaction solvent, and then introduce sulfonyl fluoride into the reaction system to carry out a chemical reaction to prepare a nitrogen nitrosated compound. The present invention uses a secondary amine compound as a reaction substrate, can successfully prepare a nitrogen nitrosated compound, realizes a new nitrogen-nitrogen single bond synthesis method to synthesize nitrosamine compounds, and has a higher yield. In addition, the synthesis method of the present invention does not need to use an oxidant or a catalyst, reduces pollution to the environment, and is simple to operate, mild reaction conditions, good substrate universality, has good functional compatibility, and uses cheap and readily available sulfonyl fluoride as a reaction promoter, which is lower in cost and can better meet the concept of green production and green chemistry.
[0090] The above-mentioned embodiments are preferred examples of the present invention and are not intended to limit the protection scope of the present invention.
Claims
1. A method for synthesizing a nitrosated compound of a secondary amine, characterized in that: The following steps are involved: Step S1, mixing the secondary amine compound and the nitro source uniformly, and then adding a solvent to obtain a mixed solution; Step S2, introducing sulfonyl fluoride into the mixed solution for reaction, obtaining a reaction solution after the reaction is completed, extracting, washing, drying, concentrating, separating and purifying the reaction solution in sequence to obtain a nitrogen nitrosated compound, Wherein, the structural formula of the nitrogen nitrosated compound is: In the structural formula, R1 and R2 are one or more of alkyl, aryl and substituted aryl. The nitro source is a metal nitrite, and the metal nitrite is sodium nitrite or potassium nitrite. The solvent is a mixed solvent of an organic solvent and water, The substituted aryl group is a methyl-substituted, methoxy-substituted, nitro-substituted or halogen-substituted aryl group.
2. The method for synthesizing the nitrosated compound of a secondary amine according to claim 1, characterized in that: in, The molar ratio of the secondary amine compound to the metal nitrite is 1:1 to 1:
100.
3. The method for synthesizing the nitrosated compound of a secondary amine according to claim 1, characterized in that: in, The volume ratio of the organic solvent to the water is 1:1 to 100:1, and the total volume of the solvent is 1 ml to 1000 ml.
4. The method for synthesizing the nitrosated compound of a secondary amine according to claim 1, characterized in that: in, In step S2, when the sulfonyl fluoride is introduced into the mixed solution for reaction, magnetic stirring is performed, and the reaction temperature is 0° C. to 100° C., and the reaction time is 1 h to 24 h.
5. The method for synthesizing the nitrosated compound of a secondary amine according to claim 1, characterized in that: in, In step S2, when the extraction is performed, the extractant is ethyl acetate, the volume of the extractant is 30 ml, and the number of extractions is 3 times.
6. The method for synthesizing the nitrosated compound of a secondary amine according to claim 1, characterized in that: in, In step S2, when the washing is performed, the detergent is a saturated sodium chloride solution, and when the drying is performed, the desiccant is anhydrous sodium sulfate.
7. The method for synthesizing the nitrosated compound of a secondary amine according to claim 1, characterized in that: in, In step S2, the concentration is concentration under reduced pressure.
8. The method for synthesizing the nitrosated compound of a secondary amine according to claim 1, characterized in that: in, In step S2, silica gel column chromatography is used for separation and purification. The silica gel mesh used in the silica gel column chromatography is 100-400 mesh, and the eluent is ethyl acetate and petroleum ether. The volume ratio of ethyl acetate to petroleum ether is 1:10-1:50.