CN114456115A - Preparation method of 3,6-diamino-1,8-naphthalimide series compounds - Google Patents
Preparation method of 3,6-diamino-1,8-naphthalimide series compounds Download PDFInfo
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Abstract
The invention provides a preparation method of 3,6-diamino-1,8-naphthalimide series compounds, relating to the technical field of chemical synthesis. The method comprises the following steps of carrying out nucleophilic addition-elimination reaction on 4-bromo-1, 8-naphthalic anhydride and an amine compound in a first solvent to obtain a first intermediate compound; in a second solvent, carrying out nitration reaction on the first intermediate compound and nitric acid under the catalytic action of concentrated sulfuric acid to obtain a second intermediate compound; and carrying out reduction reaction on the second intermediate compound and stannous chloride under the catalytic action of concentrated hydrochloric acid to obtain the 3,6-diamino-1,8-naphthalimide series compounds. The invention takes 4-bromo-1, 8-naphthalic anhydride as the starting material, and the cost of the raw material is low; the reduction process is reduced and catalyzed by concentrated hydrochloric acid and stannous chloride without Pd/C and H2The synthesis cost can be further reduced, and the operation is easy.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a preparation method of 3,6-diamino-1,8-naphthalimide series compounds.
Background
The 3,6-diamino-1,8-naphthalimide series compounds are compounds with push-pull electronic effect, have higher fluorescence quantum yield and larger Stokes shift, and are widely applied in a plurality of fields, such as fluorescent materials, fluorescent probes or fluorescent labels and the like.
The synthesis scheme of the 3,6-diamino-1,8-naphthalimide series compound mainly comprises the following steps:
1) the Rosanna Filosa project group reported a synthetic scheme of formula I (Pedubo A, Pagano B, Petronzi C, et al. design, synthesis, biological and biological students of trisustried naphthalimides as G-quadruplex ligands [ J ]. Bioorganic & medical chemistry,2011,19(21): 6419-:
2) the ChunQiong Zhou project group reported the synthetic scheme shown in formula II (Dong C, Zhou C Q, Yang J W, et al. A novel 3,6-diamino-1,8-naphthalimide derivative as a highlyselective fluorescent "turn-on" probe for colors [ J ]. RSC Advances,2015,5(42): 32990-32993.):
3) the group of Zhongyi Yuan topics reported in 2018 the synthesis scheme of formula III (Zhu G, Zhuang Y, Hu Y, et al. jointed polymers based on 1,8-naphthalene monoimide with high electron mobility [ J ]. Journal of Polymer Science Part A: Polymer Chemistry,2018,56(3): 276-:
the synthesis schemes of the 3,6-diamino-1,8-naphthalimide series compounds all use 1, 8-naphthalic anhydride or 3-nitro-1, 8-naphthalic anhydride as the starting material, and the reduction process with higher material cost needs to add H into Pd/C2Of (2) aThe method is carried out under the condition, so that the synthesis cost is further improved, the operation difficulty of the experiment is increased, the experiment is not facilitated, and the method cannot be carried out in laboratories without professional catalytic hydrogenation equipment.
Disclosure of Invention
In view of the above, the present invention aims to provide a method for preparing 3,6-diamino-1,8-naphthalimide series compounds. The preparation method provided by the invention has the advantages of low cost, easy operation and no need of Pd/C and H in the reduction process2。
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a preparation method of a 3,6-diamino-1,8-naphthalimide series compound, which comprises the following steps:
(1) carrying out nucleophilic addition-elimination reaction on 4-bromo-1, 8-naphthalic anhydride and an amine compound in a first solvent to obtain a first intermediate compound;
the amine compound has a structure shown in formula 1:
R-NH2in the formula 1, the raw material is shown in the specification,
in the formula 1, R is-CH2CH3、-CH2CH2CH3、-CH2CH2CH2CH3、-CH2CH2NH2、-CH2CH2CH2NH2、-CH2CH2OH、-CH2CH2CH2OH、-CH2CH2OCH2CH2OH or-CH2CHC8H17C10H21；
The first intermediate compound is N-R-4-bromo-1, 8-naphthalimide;
(2) in a second solvent, carrying out nitration reaction on the first intermediate compound and nitric acid under the catalytic action of concentrated sulfuric acid to obtain a second intermediate compound; the second intermediate compound is N-R-3, 6-dinitro-4-bromo-1, 8-naphthalimide;
(3) the second intermediate compound is subjected to reduction reaction in the presence of stannous chloride and concentrated hydrochloric acid to obtain a 3,6-diamino-1,8-naphthalimide series compound; the 3,6-diamino-1,8-naphthalimide series compound has a structure shown in a formula 2:
preferably, the molar ratio of the 4-bromo-1, 8-naphthalic anhydride to the amine compound in the step (1) is 1: 1.9-3; the temperature of the nucleophilic addition-elimination reaction is 79-81 ℃, and the time is 8-9 h.
Preferably, after the nucleophilic addition-elimination reaction in the step (1), the method further comprises post-treating the obtained nucleophilic addition-elimination reaction product; the post-processing method comprises the following steps:
cooling the nucleophilic addition-elimination reaction product to room temperature, and then carrying out suction filtration to obtain a solid phase substance;
recrystallizing the solid phase substance by using absolute ethyl alcohol to obtain a crystal substance;
and drying the crystal to obtain a first intermediate compound.
Preferably, the mass concentration of the nitric acid in the step (2) is 65-68%; the mass concentration of the concentrated sulfuric acid is 95-98%; the dosage ratio of the first intermediate compound, nitric acid and concentrated sulfuric acid is (0.331-0.542) g: (0.5-1.0) mL: (0.5-1.0) mL.
Preferably, the nitration reaction in the step (2) comprises a first nitration reaction stage and a second nitration reaction stage which are sequentially carried out; the temperature of the first nitration stage is 0-5 ℃, and the time is 5-6 h; the temperature of the second nitration stage is room temperature, and the time of the second nitration stage is 1-1.5 h.
Preferably, after the nitration reaction, the method further comprises the step of carrying out post-treatment on the obtained nitration reaction product; the post-processing method comprises the following steps:
quenching and filtering the nitration reaction product to obtain a solid phase substance;
washing and drying the solid phase substance in sequence to obtain a second intermediate compound; the washing detergent is acetonitrile.
Preferably, the mass concentration of the concentrated hydrochloric acid in the step (3) is 36-38%; the mass ratio of the second intermediate compound to the stannous chloride to the concentrated hydrochloric acid is (0.421-0.631) g: (2.5-3.75) g: (5-7.5) mL.
Preferably, the temperature of the reduction reaction in the step (3) is 80-85 ℃, and the time is 2-3 h.
Preferably, after the reduction reaction in the step (3), the method further comprises post-treating the obtained reduction reaction product; the post-processing method comprises the following steps:
cooling the reduction reaction product to room temperature, and then adjusting the pH value to be neutral to obtain a neutral reaction product;
extracting the neutral reaction product to obtain an organic phase; the extracting agent for extraction is dichloromethane;
and washing, concentrating and drying the organic phase sequentially to obtain the 3,6-diamino-1,8-naphthalimide series compounds.
Preferably, the first solvent is ethanol; the second solvent is concentrated sulfuric acid.
The invention provides a preparation method of a 3,6-diamino-1,8-naphthalimide series compound, which comprises the following steps: carrying out nucleophilic addition-elimination reaction on 4-bromo-1, 8-naphthalic anhydride and an amine compound in a first solvent to obtain a first intermediate compound; in a second solvent, carrying out nitration reaction on the first intermediate compound and nitric acid under the catalytic action of concentrated sulfuric acid to obtain a second intermediate compound; the second intermediate compound and stannous chloride are subjected to reduction reaction under the catalytic action of concentrated hydrochloric acid to obtain the 3,6-diamino-1,8-naphthalimide series compounds. The invention adopts 4-bromo-1, 8-naphthalic anhydride as the starting material, and the cost of the raw material is low; the reaction condition in the nitration process is mild and easy to control; in the reduction process, concentrated hydrochloric acid and stannous chloride are used for reduction and catalysis, and Pd/C and H are not needed2The method not only further reduces the synthesis cost, but also does not need catalytic hydrogenation equipment, is easy to operate and can be carried out in a common laboratory. The preparation method provided by the invention has low costLow cost, simple operation, mild condition and stable yield.
Drawings
FIG. 1 is a high resolution mass spectrum of N-butyl-3, 6-dinitro-4-bromo-1, 8-naphthalimide of example 1;
FIG. 2 is a drawing showing the preparation of N-butyl-3, 6-diamino-1,8-naphthalimide in example 11H NMR chart;
FIG. 3 is a drawing showing the preparation of N-butyl-3, 6-diamino-1,8-naphthalimide in example 113C NMR chart;
FIG. 4 is a high resolution mass spectrum of N-butyl-3, 6-diamino-1,8-naphthalimide of example 1.
Detailed Description
The invention provides a preparation method of a 3,6-diamino-1,8-naphthalimide series compound, which comprises the following steps:
(1) carrying out nucleophilic addition-elimination reaction on 4-bromo-1, 8-naphthalic anhydride and an amine compound in a first solvent to obtain a first intermediate compound;
the amine compound has a structure shown in formula 1:
R-NH2in the formula 1, the compound is shown in the specification,
in the formula 1, R is-CH2CH3、-CH2CH2CH3、-CH2CH2CH2CH3、-CH2CH2NH2、-CH2CH2CH2NH2、-CH2CH2OH、-CH2CH2CH2OH、-CH2CH2OCH2CH2OH or-CH2CHC8H17C10H21；
The first intermediate compound is N-R-4-bromo-1, 8-naphthalimide;
(2) in a second solvent, carrying out nitration reaction on the first intermediate compound and nitric acid under the catalytic action of concentrated sulfuric acid to obtain a second intermediate compound; the second intermediate compound is N-R-3, 6-dinitro-4-bromo-1, 8-naphthalimide;
(3) carrying out reduction reaction on the second intermediate compound in the presence of stannous chloride and concentrated hydrochloric acid to obtain 3,6-diamino-1,8-naphthalimide series compounds; the 3,6-diamino-1,8-naphthalimide series compound has a structure shown in a formula 2:
the method comprises the step of carrying out nucleophilic addition-elimination reaction on 4-bromo-1, 8-naphthalic anhydride and an amine compound in a first solvent to obtain a first intermediate compound. The source of the 4-bromo-1, 8-naphthalic anhydride is not particularly critical to the present invention, and commercially available products known to those skilled in the art may be used. The invention adopts 4-bromo-1, 8-naphthalic anhydride as the starting material, and the cost of the raw material is low. The source of the amine compound is not particularly limited in the present invention, and commercially available products known to those skilled in the art may be used. In the present invention, the molar ratio of the 4-bromo-1, 8-naphthalic anhydride to the amine compound is preferably 1:1.9 to 3, more preferably 1: 2. In the present invention, the first solvent is preferably ethanol, more preferably absolute ethanol; the invention has no special requirement on the adding amount of the first solvent, and can dissolve the 4-bromo-1, 8-naphthalic anhydride and the amine compound to ensure that the reaction is smoothly carried out. In the invention, the temperature of the nucleophilic addition-elimination reaction is preferably 79-81 ℃, and the time is preferably 8-9 h. In the invention, the first intermediate compound is N-R-4-bromo-1, 8-naphthalimide, R in the N-R-4-bromo-1, 8-naphthalimide is consistent with R in the structure of the amine compound shown in the formula 1, and the amine compound is NH2CH2CH2CH2CH3(i.e., N-butylamine) as an example, the first intermediate compound obtained in the reaction is N-butyl-4-bromo-1, 8-naphthalimide. In the present invention, the specific operation method of the nucleophilic addition-elimination reaction is preferably: dissolving 4-bromo-1, 8-naphthalic anhydride in a first solvent to obtain a 4-bromo-1, 8-naphthalic anhydride solution; adding amine compounds into the 4-bromo-1, 8-naphthalic anhydride solution, mixing, and performing condensation refluxReacting to obtain a first intermediate compound. In the present invention, the nucleophilic addition-elimination reaction has the formula shown in formula IV:
after the nucleophilic addition-elimination reaction, the present invention also preferably subjects the resulting nucleophilic addition-elimination reaction product to a post-treatment; the method of post-treatment preferably comprises the steps of:
cooling the nucleophilic addition-elimination reaction product to room temperature, and then carrying out suction filtration to obtain a solid phase substance;
recrystallizing the solid phase substance by using absolute ethyl alcohol to obtain a crystal substance;
and drying the crystal to obtain a first intermediate compound.
The present invention does not require any particular type of cooling, and may be carried out by cooling methods known to those skilled in the art, such as natural cooling. The present invention does not require any particular method for drying, and drying to a constant weight may be carried out by a drying method known to those skilled in the art.
After a first intermediate compound is obtained, carrying out nitration reaction on the first intermediate compound and nitric acid in a second solvent under the catalytic action of concentrated sulfuric acid to obtain a second intermediate compound; the second intermediate compound is N-R-3, 6-dinitro-4-bromo-1, 8-naphthalimide. In the invention, the mass concentration of the nitric acid is preferably 65-68%; the mass concentration of the concentrated sulfuric acid is preferably 95-98%; the dosage ratio of the first intermediate compound, nitric acid and concentrated sulfuric acid is preferably (0.331-0.542) g: (0.5-1.0) mL: (0.5-1.0) mL. In the invention, the second solvent is preferably concentrated sulfuric acid, and the mass concentration of the concentrated sulfuric acid is preferably 95-98%; in the present invention, the amount of the second solvent to be added is not particularly limited, and the first intermediate compound may be dissolved. In the present invention, the nitration reaction preferably includes a first nitration reaction stage and a second nitration reaction stage which are sequentially performed; the temperature of the first nitration stage is preferably 0-5 ℃, and the time is preferably 5-6 h; the temperature of the second nitration stage is room temperature, and the time of the second nitration stage is preferably 1-1.5 h. In the invention, the nitration reaction condition is mild and easy to control. In the present invention, the specific operation method of the nitration reaction is preferably: dissolving the first intermediate compound in a second solvent under the conditions of ice-water bath at 0-5 ℃ and stirring to obtain a first intermediate compound solution; dropwise adding a mixed solution of nitric acid and concentrated sulfuric acid into the first intermediate compound solution to perform a first nitration reaction stage; after the first nitration stage is finished, removing the ice water bath, and heating to room temperature to carry out a second nitration stage; the room temperature is specifically 25 ℃. In the invention, the time of the first nitration stage is calculated by the completion of the dropwise addition of the mixed solution of nitric acid and concentrated sulfuric acid; the time of the second nitration stage is the reaction time at room temperature after removing the ice water bath and raising the temperature to room temperature. In the present invention, the reaction formula of the nitration reaction is shown in formula V:
after the nitration reaction, the invention also preferably carries out post-treatment on the obtained nitration reaction product; the method of post-treatment preferably comprises the steps of:
quenching and filtering the nitration reaction product to obtain a solid phase substance;
washing and drying the solid phase substance in sequence to obtain a second intermediate compound; the washing detergent is acetonitrile.
In the present invention, it is preferable to add ice water to the nitration product for quenching. In the invention, the temperature of the acetonitrile is preferably 5-10 ℃. The present invention does not require any particular method for drying, and drying to a constant weight may be carried out by a drying method known to those skilled in the art.
After the second intermediate compound is obtained, the second intermediate compound is subjected to reduction reaction in the presence of stannous chloride and concentrated hydrochloric acid to obtain 3The 6-diamino-1,8-naphthalimide series of compounds. In the invention, the mass concentration of the concentrated hydrochloric acid is preferably 36-38%, the concentrated hydrochloric acid provides an acidic environment, the solubility of stannous chloride is increased, and the hydrolysis of the stannous chloride is inhibited; the mass ratio of the second intermediate compound to the stannous chloride to the concentrated hydrochloric acid is preferably (0.421-0.631) g: (2.5-3.75) g: (5-7.5) mL. In the invention, the temperature of the reduction reaction is preferably 80-85 ℃, and the time is preferably 2-3 h. In the present invention, the specific operation method of the reduction reaction is preferably: dissolving the second intermediate compound in concentrated hydrochloric acid to obtain a second intermediate compound solution; under the condition of stirring, dropwise adding a concentrated hydrochloric acid solution of stannous chloride into the second intermediate compound solution to obtain a mixed solution; and condensing and refluxing the mixed solution at the temperature of 80-85 ℃ for reduction reaction. In the invention, the time of the reduction reaction is calculated by the time of adding stannous chloride. In the invention, the 3,6-diamino-1,8-naphthalimide series compound has a structure shown in a formula 2, R in the structure shown in the formula 2 is consistent with R in the formula 1, and the amine compound is NH2CH2CH2CH2CH3(i.e., N-butylamine) as an example, the 3,6-diamino-1,8-naphthalimide series of compounds obtained by the reaction is N-butyl-3, 6-diamino-1, 8-naphthalimide. In the invention, the reduction reaction process is reduced and catalyzed by concentrated hydrochloric acid and stannous chloride without Pd/C and H2Not only further reduces the synthesis cost, but also is easy to operate. In the present invention, the reaction formula of the reduction reaction is represented by formula VI:
after the reduction reaction, the invention also preferably carries out post-treatment on the obtained reduction reaction product; the method of post-treatment preferably comprises the steps of:
cooling the reduction reaction product to room temperature, and then adjusting the pH value to be neutral to obtain a neutral reaction product;
extracting the neutral reaction product to obtain an organic phase; the extractant for extraction is Dichloromethane (DCM);
and washing, concentrating and drying the organic phase sequentially to obtain the 3,6-diamino-1,8-naphthalimide series compounds.
The present invention does not require any particular cooling means, such as natural cooling, as is well known to those skilled in the art. In the present invention, the concentration method is preferably rotary evaporation, and the present invention preferably concentrates the organic phase to dryness by rotary evaporation. In the present invention, the drying is preferably vacuum drying, and the present invention does not require any particular temperature or time for the drying, and the drying may be carried out to a constant weight.
The preparation method of the 3,6-diamino-1,8-naphthalimide series compounds provided by the invention has the advantages of low cost, simple operation, mild condition and stable yield.
The following examples are provided to illustrate the preparation of 3,6-diamino-1,8-naphthalimide compounds of the present invention in detail, but they should not be construed as limiting the scope of the invention.
Example 1
The preparation of N-butyl-3, 6-diamino-1,8-naphthalimide has a route shown in formula VII:
the preparation method comprises the following steps:
(1) 4-bromo-1, 8-naphthalic anhydride (3.5g, 12.6mmol) was dissolved in 30mL of anhydrous ethanol, 1.35mL (25mmol) of n-butylamine was added, and the reaction was refluxed at 80 ℃ for 8 h; after the reaction is finished, cooling to room temperature, performing suction filtration to obtain a solid phase, recrystallizing with absolute ethyl alcohol, and drying to obtain 3.132g N-butyl-4-bromo-1, 8-naphthalimide yellow flocculent solid with the yield of 95.1%.
(2) Dissolving N-butyl-4-bromo-1, 8-naphthalimide (0.480g, 1.45mmol) in 2mL of concentrated sulfuric acid (98% by mass) at 0 ℃ under magnetic stirringThen 0.5mL of HNO was added dropwise thereto at 0 deg.C3(67% by mass) and 0.5mL of H2SO4(the mass concentration is 98 percent), and reacting for 5 hours at 0 ℃ after the dropwise addition is finished; the ice-water bath was removed and the reaction was continued for 1h at room temperature. After the reaction is finished, ice water is added to quench the reaction, a solid phase is obtained by suction filtration, the solid phase is washed by a cold acetonitrile solvent, and the light yellow solid of 0.288g N-butyl-3, 6-dinitro-4-bromo-1, 8-naphthalimide is obtained after drying, the yield is 47.2 percent, and a high-resolution mass spectrum chart is shown in figure 1.
(3) N-butyl-3, 6-dinitro-4-bromo-1, 8-naphthalimide (0.526g, 1.25mmol) is dissolved in 2mL of concentrated hydrochloric acid (mass concentration: 37%), 2.5g of stannous chloride solution dissolved in 3mL of concentrated hydrochloric acid (mass concentration: 37%) is added dropwise under stirring, and the mixture is condensed and refluxed at 80 ℃ for 2 hours. After the reaction is finished, cooling to room temperature, adjusting the pH value to be neutral, extracting with dichloromethane and water, transferring a lower organic phase, carrying out spin drying with a rotary evaporator, carrying out vacuum drying to obtain a yellow crude product, recrystallizing with absolute ethyl alcohol to obtain 0.180g N-butyl-3, 6-diamino-1,8-naphthalimide, wherein the yield is 50.8%, the purity is more than 98%, the nuclear magnetic hydrogen spectrum, the carbon spectrum and the mass spectrum of the product are respectively shown as in fig. 2, fig. 3 and fig. 4, and the nuclear magnetic hydrogen spectrum, the carbon spectrum and the mass spectrum data are as follows:
1H NMR(400MHz,DMSO-d6)δ7.63(s,2H),6.98(s,2H),5.72(s,4H),4.12–3.95(m,2H),1.62(p,J＝7.5Hz,2H),1.38(h,J＝7.3Hz,2H),0.97(t,J＝7.3Hz,3H).
13C NMR(100MHz,DMSO-d6)δ163.26,146.97,134.88,121.69,116.31,113.81,108.95,38.27,29.09,19.15,13.07.
ESI-MS m/z:284.1398([M+H]+) Calculating the value: 284.1399.
example 2
The preparation method of the N-aminoethyl-3, 6-diamino-1,8-naphthalimide has a route shown in a formula VIII:
the preparation method comprises the following steps:
(1) 4-bromo-1, 8-naphthalic anhydride (3.5g, 12.6mmol) is dissolved in 30mL of anhydrous ethanol, 1.69mL (25mmol) of ethylenediamine is added, and the mixture is subjected to condensation reflux reaction at 80 ℃ for 8 hours; after the reaction is finished, cooling to room temperature, performing suction filtration to obtain a solid phase, recrystallizing with absolute ethyl alcohol, and drying to obtain 3.654g N-aminoethyl-4-bromo-1, 8-naphthalimide yellow flocculent solid with the yield of 91.2%.
(2) Dissolving N-aminoethyl-4-bromo-1, 8-naphthalimide (0.461g, 1.45mmol) in 2mL of concentrated sulfuric acid (98% by mass) under magnetic stirring at 0 deg.C, and dropwise adding 0.5mL of HNO thereto at 0 deg.C3(67% by mass) and 0.5mL of H2SO4(the mass concentration is 98 percent), and reacting for 5 hours at 0 ℃ after the dropwise addition is finished; the ice-water bath was removed and the reaction was continued for 1h at room temperature. After the reaction is finished, ice water is added to quench the reaction, a solid phase is obtained by suction filtration, the solid phase is washed by a cold acetonitrile solvent, and the light yellow solid of 0.275g N-aminoethyl-3, 6-dinitro-4-bromo-1, 8-naphthalimide is obtained after drying, wherein the yield is 46.5%.
(3) N-aminoethyl-3, 6-dinitro-4-bromo-1, 8-naphthalimide (0.510g, 1.25mmol) was dissolved in 2mL of concentrated hydrochloric acid (37% by mass), and 2.5g of stannous chloride solution dissolved in 3mL of concentrated hydrochloric acid (37% by mass) was added dropwise with stirring, and the mixture was condensed and refluxed at 80 ℃ for 2 hours. After the reaction is finished, cooling to room temperature, adjusting the pH value to be neutral, extracting with dichloromethane and water, transferring a lower organic phase, drying by a rotary evaporator, drying in vacuum to obtain a yellow crude product, and recrystallizing with absolute ethyl alcohol to obtain 0.166g of N-aminoethyl-3, 6-diamino-1,8-naphthalimide with the yield of 49.1%.
Example 3
The preparation of N-hydroxyethyl-3, 6-diamino-1,8-naphthalimide is shown in formula IX:
the preparation method comprises the following steps:
(1) dissolving 4-bromo-1, 8-naphthalic anhydride (3.5g, 12.6mmol) in 30mL of anhydrous ethanol, adding 1.55mL (25mmol) of 2-hydroxyethylamine, and carrying out condensation reflux reaction at 80 ℃ for 8 h; after the reaction is finished, cooling to room temperature, obtaining a solid phase by suction filtration, recrystallizing by absolute ethyl alcohol, and drying to obtain 3.706g N-hydroxyethyl-4-bromo-1, 8-naphthalimide yellow flocculent solid with the yield of 92.2%.
(2) Dissolving N-hydroxyethyl-4-bromo-1, 8-naphthalimide (0.462g, 1.45mmol) in 2mL of concentrated sulfuric acid (98% by mass) under magnetic stirring at 0 ℃, and then dropwise adding 0.5mL of HNO thereto at 0 ℃3(67% by mass) and 0.5mL of H2SO4(the mass concentration is 98%) and reacting for 5h at 0 ℃ after the dropwise addition; the ice-water bath was removed and the reaction was continued for 1h at room temperature. After the reaction is finished, ice water is added to quench the reaction, a solid phase is obtained by suction filtration, and the solid phase is washed by a cold acetonitrile solvent and dried to obtain 0.278g of N-ethoxyl-3, 6-dinitro-4-bromine-1, 8-naphthalimide light yellow solid with the yield of 46.8 percent.
(3) N-hydroxyethyl-3, 6-dinitro-4-bromo-1, 8-naphthalimide (0.511g, 1.25mmol) is dissolved in 2mL of concentrated hydrochloric acid (mass concentration: 37%), 2.5g of stannous chloride solution dissolved in 3mL of concentrated hydrochloric acid (mass concentration: 37%) is added dropwise under stirring, and the mixture is condensed and refluxed at 80 ℃ for 2 hours. After the reaction is finished, cooling to room temperature, adjusting the pH value to be neutral, extracting with dichloromethane and water, transferring a lower organic phase, drying by a rotary evaporator, drying in vacuum to obtain a yellow crude product, and recrystallizing with absolute ethyl alcohol to obtain 0.162g of N-hydroxyethyl-3, 6-diamino-1,8-naphthalimide, wherein the yield is 47.9%.
As can be seen from the above examples, the invention adopts 4-bromo-1, 8-naphthalic anhydride as the starting material, and the cost of the raw material is low; the reaction condition in the nitration process is easy to control and mild; in the reduction process, concentrated hydrochloric acid and stannous chloride are used for reduction and catalysis, and Pd/C and H are not needed2Not only further reduces the synthesis cost, but also is easy to operate. The preparation method of the 3,6-diamino-1,8-naphthalimide series compounds provided by the invention has the advantages of low cost, simple operation and stripThe temperature is moderate.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. A method for preparing 3,6-diamino-1,8-naphthalimide series compounds is characterized by comprising the following steps:
(1) carrying out nucleophilic addition-elimination reaction on 4-bromo-1, 8-naphthalic anhydride and an amine compound in a first solvent to obtain a first intermediate compound;
the amine compound has a structure shown in formula 1:
R-NH2in the formula 1, the compound is shown in the specification,
in the formula 1, R is-CH2CH3、-CH2CH2CH3、-CH2CH2CH2CH3、-CH2CH2NH2、-CH2CH2CH2NH2、-CH2CH2OH、-CH2CH2CH2OH、-CH2CH2OCH2CH2OH or-CH2CHC8H17C10H21；
The first intermediate compound is N-R-4-bromo-1, 8-naphthalimide;
(2) in a second solvent, carrying out nitration reaction on the first intermediate compound and nitric acid under the catalytic action of concentrated sulfuric acid to obtain a second intermediate compound; the second intermediate compound is N-R-3, 6-dinitro-4-bromo-1, 8-naphthalimide;
(3) carrying out reduction reaction on the second intermediate compound in the presence of stannous chloride and concentrated hydrochloric acid to obtain a 3,6-diamino-1,8-naphthalimide series compound; the 3,6-diamino-1,8-naphthalimide series compound has a structure shown in a formula 2:
2. the preparation method according to claim 1, wherein the molar ratio of the 4-bromo-1, 8-naphthalic anhydride to the amine compound in step (1) is 1: 1.9-3; the temperature of the nucleophilic addition-elimination reaction is 79-81 ℃, and the time is 8-9 h.
3. The production method according to claim 1 or 2, wherein the step (1) further comprises, after the nucleophilic addition-elimination reaction, post-treating the resulting product of the nucleophilic addition-elimination reaction; the post-processing method comprises the following steps:
cooling the nucleophilic addition-elimination reaction product to room temperature, and then carrying out suction filtration to obtain a solid phase substance;
recrystallizing the solid phase substance by using absolute ethyl alcohol to obtain a crystal substance;
and drying the crystal to obtain a first intermediate compound.
4. The preparation method according to claim 1, wherein the mass concentration of the nitric acid in the step (2) is 65-68%; the mass concentration of the concentrated sulfuric acid is 95-98%; the dosage ratio of the first intermediate compound, nitric acid and concentrated sulfuric acid is (0.331-0.542) g: (0.5-1.0) mL: (0.5-1.0) mL.
5. The production method according to claim 1, wherein the nitration reaction in the step (2) comprises a first nitration reaction stage and a second nitration reaction stage which are sequentially carried out; the temperature of the first nitration stage is 0-5 ℃, and the time is 5-6 h; the temperature of the second nitration stage is room temperature, and the time of the second nitration stage is 1-1.5 h.
6. The production method according to claim 1, 4 or 5, characterized by further comprising, after the nitration reaction, post-treating the obtained nitration reaction product; the post-processing method comprises the following steps:
quenching and filtering the nitration reaction product to obtain a solid phase substance;
washing and drying the solid phase substance in sequence to obtain a second intermediate compound; the washing detergent is acetonitrile.
7. The preparation method according to claim 1, characterized in that the mass concentration of the concentrated hydrochloric acid in the step (3) is 36-38%; the mass ratio of the second intermediate compound to the stannous chloride to the concentrated hydrochloric acid is (0.421-0.631) g: (2.5-3.75) g: (5-7.5) mL.
8. The preparation method according to claim 1, wherein the temperature of the reduction reaction in the step (3) is 80-85 ℃ and the time is 2-3 h.
9. The production method according to claim 1, 7 or 8, characterized in that after the reduction reaction in the step (3), the method further comprises post-treating the resulting reduction reaction product; the post-processing method comprises the following steps:
cooling the reduction reaction product to room temperature, and then adjusting the pH value to be neutral to obtain a neutral reaction product;
extracting the neutral reaction product to obtain an organic phase; the extracting agent for extraction is dichloromethane;
and washing, concentrating and drying the organic phase in sequence to obtain the 3,6-diamino-1,8-naphthalimide series compounds.
10. The production method according to claim 1, wherein the first solvent is ethanol; the second solvent is concentrated sulfuric acid.
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