A method of synthesizing an asymmetrically substituted reaction intermediate
A one-pot synthesis method was used to achieve controllable asymmetric substitution of conjugated molecules under mild conditions, solving the problem of controllable asymmetric substitution of the three arms of star-shaped aromatics, providing a functional modification pathway for aldehyde groups, and improving the diversity and efficiency of optoelectronic materials.
Patent Information
- Application Number
- CN202310367628.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-04-07
- Publication Date
- 2026-02-06
- Estimated Expiration
- 2043-04-07
AI Technical Summary
Existing technologies make it difficult to achieve controllable asymmetric substitution of conjugated molecules with multiple rotational axial symmetries, especially controllable asymmetric substitution of the three arms of star-shaped aromatics, which affects the research and application of their optoelectronic materials.
A one-pot synthesis method using bromine-substituted conjugated molecules with multiple rotational axes of symmetry and aldehyde-containing arylboronic acid/boronic esters under conventional Suzuki reaction conditions was adopted. By adjusting the reaction conditions and feed ratio, the controllable synthesis of asymmetric substitution reaction intermediates was achieved.
Controllable asymmetric substitution of conjugated molecules was achieved under mild conditions, the yield of different numbers of substituents was adjusted, a functional modification pathway for aldehyde groups was provided, and the diversity and efficiency of optoelectronic materials were improved.
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Figure CN116574117B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing an asymmetrically substituted reaction intermediate. BACKGROUND
[0002] Organic semiconductor materials have many advantages such as complex and variable types, convenient structural design, convenient preparation and processing, and low application cost. Through the design of the structure of organic molecules, specific functions can be realized in response to environmental factors such as light, electricity, sound, heat, force and chemistry. Conjugated molecules with multiple rotational axis symmetry have three or more identical branch structures, more skeleton branches and active sites than linear molecules, and higher molar extinction coefficients, so they are popular molecules in the research of organic semiconductor materials. In the design and development of such molecules with multiple identical branch structures, substitution at the peripheral active sites is a common modification method. Taking star-shaped molecules with triple rotational axis symmetry as an example, some star-shaped molecules with different peripheral group substitutions and synthesis methods are shown below (J. Mater. Chem., 2005, 15, 2393-2398 | 2393, Adv. Funct. Mater. 2005, 15, No. 5, May, Chem. Eur. J. 2017, 23, 11611-11619). As can be seen, these synthesis methods are based on the symmetric substitution of star-shaped arenes. Due to the equivalence of the three-arm active sites of star-shaped arenes, it is difficult to achieve controllable asymmetric substitution of the three arms of star-shaped arenes by common synthesis methods. In addition, each branch of the molecule with multiple rotational axis symmetry has different influences on the photophysical properties and charge properties of the molecule, so the asymmetrically substituted derivatives of such molecules have broad research prospects in the field of optoelectronic materials. Therefore, it is necessary to develop a simple, efficient and universal asymmetric substitution synthesis method for conjugated molecules with multiple rotational axis symmetry.
[0003]
[0004] (a-c) Structure and synthesis method of star-shaped conjugated molecules with phenyl, triazine and fused ring arene as core SUMMARY
[0005] In view of the deficiencies in the prior art, one of the purposes of the present application is to provide a method for synthesizing an asymmetrically substituted reaction intermediate; a one-pot synthesis method for controllable asymmetric substitution between a bromine-substituted conjugated molecule with multiple rotational axis symmetry and an aldehyde-containing boronic acid / boronic acid ester.
[0006] The second purpose of the present application is to provide a method for adjusting the yield of target molecules with different numbers of substituents based on the above synthesis route.
[0007] The conjugated molecule with multiple rotational axis symmetry of the present application can be a star molecule, a triangular molecule, a polygonal molecule, etc. Specifically, the present application is illustrated by taking the reaction of a star azine molecule with triple rotational axis symmetry with 5-aldehyde-2-thiophene boronic acid as an example. The star azine molecule (NSA) was first reported by Xie's group in 2018 (Gao, H. Design and synthesis of luminescent materials based on BODIPY and B-N coordination chelates and their photophysical properties. [D]. South China University of Technology, 2018), which was synthesized by taking cyanuric chloride as the core and obtained by symmetric substitution. First, a star azine molecule with three bromine groups is prepared by a similar symmetric substitution route, and then under the mild conditions of a conventional Suzuki reaction, Suzuki coupling reaction and aldehyde group catalyzed hydrogenation substitution reaction occur simultaneously, and aldehyde group thiophene group monosubstituted, aldehyde group thiophene group disubstituted, aldehyde group thiophene group trisubstituted molecules are obtained in one step. Further, by optimizing the reaction conditions and adjusting the feed ratio, the yield of molecules with different number of substituents is adjusted.
[0008] In addition, the molecules synthesized by this route contain aldehyde groups on the outside, and the aldehyde group, as a group with high reactivity, can be conveniently functionalized and modified. As follows, two functionalization and modification routes of aldehyde groups are provided, using 3-(dicyanomethylene) indanone and melamine to react with aldehyde groups, respectively. The former can form the end group structure (IC end group) commonly used in solar cell acceptor materials, and the latter can introduce a diamino triazine group to construct a hydrogen-bonded organic framework material (HOF).
[0009]
[0010] (a-b) Two functionalization and modification routes of the aldehyde-containing intermediates synthesized by the present application
[0011] The technical solution adopted by the present application is:
[0012] A method for synthesizing an asymmetrically substituted reaction intermediate, which is a one-pot synthesis of controllable asymmetric substitution of a bromine-substituted conjugated molecule with multiple rotational axis symmetry and an aldehyde-containing aryl boronic acid / aryl borate, the reaction general formula is as follows:
[0013]
[0014] Wherein, n is an integer of 3 and above, and ○ is a conjugated molecule with n-fold rotational axis symmetry; Ar is an aromatic group in an aldehyde-containing aryl boronic acid / aryl borate; the product is an aldehyde-containing aryl monosubstituted, disubstituted, …, n-substituted conjugated molecule.
[0015] Preferably, the conjugated molecule with n-fold rotational axis symmetry has the following structure:
[0016]
[0017] wherein Ar1-Ar4 are conjugated aryl groups, and the bromination sites are at the hydrogen-containing sites of the conjugated aryl groups.
[0018] Further preferably, the conjugated aryl groups include thiophene, thiazole, pyrazole, pyridine, pyrimidine, pyrazine, pyridazine, triazine, thiazine, phenyl, and carbazole.
[0019] Preferably, the aromatic groups include thiophene, thiazole, pyrazole, pyridine, pyrimidine, pyrazine, pyridazine, triazine, thiazine, phenyl, and carbazole.
[0020] Preferably, the method for synthesizing the asymmetrically substituted reaction intermediate comprises the following steps: under conventional Suzuki reaction conditions, obtaining the asymmetrically substituted reaction intermediate by one-pot reaction of the aldehyde-containing aryl boronic acid / ester and the bromine-substituted conjugated molecule with multiple rotational axis symmetry.
[0021] Preferably, the bromine-substituted conjugated molecule with multiple rotational axis symmetry is a star-shaped azine molecule with three-fold rotational axis symmetry, and the aldehyde-containing aryl boronic acid / ester is 5-aldehyde-2-thiophene boronic acid.
[0022] Further preferably, the synthesis route is as follows:
[0023]
[0024] Further preferably, the method for synthesizing the asymmetrically substituted reaction intermediate comprises the following steps: adding the star-shaped azine molecule with three-fold rotational axis symmetry, 5-aldehyde-2-thiophene boronic acid, potassium carbonate, and solvent into a reaction vessel, connecting a condenser, and adding a palladium catalyst under inert atmosphere; and then placing the reaction vessel in an oil bath for heating to perform the reaction, to obtain three intermediates: the star-shaped azine molecule with aldehyde-thiophenyl group mono-substitution, aldehyde-thiophenyl group di-substitution, and aldehyde-thiophenyl group tri-substitution.
[0025] More preferably, the molar ratio of the star-shaped azine molecule with three-fold rotational axis symmetry and 5-aldehyde-2-thiophene boronic acid is 1:2-8; the palladium catalyst is tetrakis(triphenylphosphine)palladium; the amount of the palladium catalyst is 3% of the molar amount of the star-shaped azine molecule with three-fold rotational axis symmetry; the reaction temperature is 80-110°C, and the reaction time is 12-24h.
[0026] More preferably, the inert atmosphere is argon.
[0027] More preferably, the potassium carbonate is used in the form of a 2 mol / L aqueous solution.
[0028] More preferably, the solvent is a mixture of toluene, ethanol and water, the volume ratio of toluene, ethanol and water is 3:1:1, the amount of toluene, ethanol and water is 30ml, 10ml and 10ml respectively, the reaction temperature is 85℃, and the 5-aldehyde-2-thiophene boronic acid is 3-3.3 times of the equivalent of the star azine molecule with three-fold rotational axis symmetry, so that the star azine molecule with mono-, di- and tri- aldehyde-thiophene group substitution can be obtained.
[0029] More preferably, the solvent is a mixture of toluene, ethanol and water, the volume ratio of toluene, ethanol and water is 3:1:1, the amount of toluene, ethanol and water is 30ml, 10ml and 10ml respectively, the reaction temperature is 80-85℃, and the 5-aldehyde-2-thiophene boronic acid is 2-2.5 times of the equivalent of the star azine molecule with three-fold rotational axis symmetry, so that the star azine molecule with mono- aldehyde-thiophene group substitution has the highest yield;
[0030] More preferably, the solvent is a mixture of toluene, ethanol and water, the volume ratio of toluene, ethanol and water is 3:1:1, the amount of toluene, ethanol and water is 30ml, 10ml and 10ml respectively, the reaction temperature is 85-100℃, and the 5-aldehyde-2-thiophene boronic acid is 4-6 times of the equivalent of the star azine molecule with three-fold rotational axis symmetry, so that the star azine molecule with di- aldehyde-thiophene group substitution has the highest yield;
[0031] More preferably, the solvent is toluene, the amount of toluene is 40ml, the reaction temperature is 110℃, and the 5-aldehyde-2-thiophene boronic acid is 7-8 times of the equivalent of the star azine molecule with three-fold rotational axis symmetry, so that the star azine molecule with tri- aldehyde-thiophene group substitution has the highest yield.
[0032] The present application has the following advantages:
[0033] The present application can realize the controllable asymmetric substitution of the conjugated molecule with multiple rotational axis symmetry through one-step synthesis reaction under mild reaction conditions, and further adjusting the reaction conditions and the feeding ratio can adjust the yield of the product with different number of substitutions. BRIEF DESCRIPTION OF DRAWINGS
[0034] Figure 1 The reaction general formula for realizing the controllable asymmetric substitution is provided.
[0035] Figure 2a The nuclear magnetic resonance hydrogen spectrum of the product 5-CHO-Th-NSA-1 obtained in Example 1.
[0036] Figure 2bNMR spectrum of hydrogen of the product 5-CHO-Th-NSA-2 obtained in Example 1.
[0037] Figure 2c NMR spectrum of hydrogen of the product 5-CHO-Th-NSA-3 obtained in Example 1.
[0038] Figure 3 Crystal structure of the product 5-CHO-Th-NSA-1 / 3 obtained in Example 1 (top view and side view of molecular conformation in single crystal structure). DETAILED DESCRIPTION
[0039] The present application will be described in detail below with reference to the drawings and specific examples, which are intended to help better understand the content of the present application. The present examples are implemented on the premise of the technical solutions of the present application, and detailed implementation manners and specific operation steps are given, but these implementation manners do not limit the protection scope of the present application in any way.
[0040] The practice of the present application can employ conventional techniques of compound chemistry within the skill of the art. In the following examples, efforts have been made to ensure the accuracy of the numbers (including amounts, temperature, reaction times, etc.) presented, but some experimental error and deviation should be accounted for; temperature is in degrees Celsius in the following examples, and pressure is at or near atmospheric pressure. All solvents are purchased as analytical or chromatographic grade, and all reactions are carried out under an argon inert atmosphere. Unless otherwise indicated, all reagents are commercially available.
[0041] The reaction scheme for realizing the controllable asymmetric substitution provided by the present application is as follows Figure 1 .
[0042] The present application first uses a conventional substitution method to prepare a symmetric brominated conjugated molecule with multiple rotation axis symmetry, and then realizes controllable asymmetric substitution on the brominated molecule by using an aryl boronic acid / ester containing aldehyde.
[0043] Preferably, the synthesis method has the reaction route as shown in the following formula:
[0044]
[0045] Under the conditions of a conventional Suzuki reaction, the Suzuki coupling reaction and the catalytic hydrogenation substitution reaction of the aldehyde group occur simultaneously, and three intermediates: star-shaped azine molecules with aldehyde thienyl group single substitution, aldehyde thienyl group double substitution, and aldehyde thienyl group triple substitution are synthesized in one step.
[0046] Preferably, the coupling reaction is carried out in a mixed solvent of toluene, ethanol and aqueous potassium carbonate solution, the reaction temperature is 85°C, and the feeding amount of 5-aldehyde-2-thiophene boronic acid is 3.1 times of the equivalent amount, so as to obtain the star-shaped azine molecule with mono-substituted aldehyde-thiophene group, di-substituted aldehyde-thiophene group and tri-substituted aldehyde-thiophene group.
[0047] Preferably, the coupling reaction is carried out in a mixed solvent of toluene, ethanol and aqueous potassium carbonate solution, the reaction temperature is 85°C, and the feeding amount of 5-aldehyde-2-thiophene boronic acid is 2 times of the equivalent amount, so as to obtain the star-shaped azine molecule with mono-substituted aldehyde-thiophene group.
[0048] Preferably, the coupling reaction is carried out in a mixed solvent of toluene, ethanol and aqueous potassium carbonate solution, the reaction temperature is 85°C, and the feeding amount of 5-aldehyde-2-thiophene boronic acid is 5 times of the equivalent amount, so as to obtain the star-shaped azine molecule with di-substituted aldehyde-thiophene group.
[0049] Preferably, the coupling reaction is carried out in a mixed solvent of toluene, ethanol and aqueous potassium carbonate solution, the reaction temperature is 85°C, and the feeding amount of 5-aldehyde-2-thiophene boronic acid is 5 times of the equivalent amount, so as to obtain the star-shaped azine molecule with di-substituted aldehyde-thiophene group.
[0050] The crystal structure of the product 5-CHO-Th-NSA-1 / 3 (top view and side view of the molecular conformation in the single crystal structure) is as follows: Figure 3 .
[0051] Example 1:
[0052] The synthesis route of the asymmetric substitution based on the star-shaped azine molecule (NSA) is as follows:
[0053]
[0054] The synthesis of 5-Br-NSA adopts the conventional symmetric substitution method, which is not described here.
[0055] One-pot synthesis steps of the star-shaped azine molecule with different number of aldehyde-thiophene groups:
[0056] In a 100 ml round bottom flask, 108 mg (0.1 mmol) of 5-Br-NSA, 49 mg (0.31 mmol) of 5- aldehyde-2-thiopheneboronic acid, 30 ml of anhydrous toluene, 10 ml of anhydrous ethanol, 10 ml of 2M potassium carbonate solution were added, and the condenser was connected and sealed. Then the round bottom flask was frozen in liquid nitrogen until the liquid was completely frozen, and the oxygen in the bottle was removed by pumping for several minutes, then argon was introduced into the bottle, and the round bottom flask was placed in ethanol for thawing. After repeating the above steps three times, open the device, quickly add 3.5 mg of tetrakis(triphenylphosphine)palladium, and repeat the air exchange step once. Heat and stir at 85°C under argon for 12 h. After the reaction was completed, there was a blue-black precipitate at the bottom of the round bottom flask, and the upper layer was a yellow-green transparent solution. The product was transferred to a separatory funnel and extracted with dichloromethane and water, repeated 3 times, the organic phase was collected and rotary evaporated, then dissolved in a small amount of dichloromethane and separated and purified by silica gel column chromatography. First use DCM:PE = 1:1 mixed solvent as developing agent, then change the mixed solvent ratio to DCM:PE = 3:1, and finally use THF:PE = 2:1 mixed solvent as developing agent, three yellow-green products can be obtained in turn. The three products were identified as 5-CHO-Th-NSA-1, 5-CHO-Th-NSA-2 and 5-CHO-Th-NSA-3 by nuclear magnetic resonance and mass spectrometry.
[0057] 5-CHO-NSA-1 NMR hydrogen spectrum Figure 2a ) and mass spectrum: 1 H NMR (500 MHz, DMSO-d6) δ 9.84 (s, 1H), 8.15 (dd, J = 8.8, 2.4 Hz, 1H), 7.96 (d, J = 4.0 Hz, 1H), 7.77 - 7.69 (m, 3H), 7.62 - 7.57 (m, 2H), 7.45 (d, J = 4.0 Hz, 1H), 7.39 - 7.31 (m, 12H), 7.25 - 7.13 (m, 18H), 6.97 - 6.88 (m, 2H), 6.22 (dt, J = 8.5, 2.3 Hz, 3H). MALDI-TOF MS: calcd. 959.5530; found 883.413 [M-Ph] + (100%), 960.554 [M+H] + (40%).
[0058] 5-CHO-NSA-2 NMR hydrogen spectrum Figure 2b ) and mass spectrum: 1H NMR (400 MHz, DMSO-d6) δ 9.84 (s, 2H), 8.18 (ddd, J = 8.8, 3.8, 2.4 Hz, 2H), 7.96 (dd, J = 4.0, 1.0 Hz, 2H), 7.81 - 7.72 (m, 3H), 7.62 (dd, J = 6.3, 1.8 Hz, 1H), 7.46 (dd, J = 4.0, 1.2 Hz, 2H), 7.40 - 7.31 (m, 12H), 7.28 - 7.15 (m, 18H), 6.29 - 6.19 (m, 3H). MALDI-TOF MS: calcd. 1069.6830; found 993.584 [M-Ph] + (100%), 1070.708 [M+H] + (30%).
[0059] 5-CHO-Th-NSA-3 NMR hydrogen spectrum Figure 2c and mass spectrum: 1 H NMR (400 MHz, DMSO-d6) δ 9.84 (s, 3H), 8.21 (dd, J = 8.9, 2.4 Hz, 3H), 7.97 (d, J = 4.0 Hz, 3H), 7.80 (d, J = 2.4 Hz, 3H), 7.48 (d, J = 4.0 Hz, 3H), 7.41 - 7.35 (m, 12H), 7.26 - 7.16 (m, 18H), 6.25 (d, J = 8.8 Hz, 3H). MALDI-TOF MS: calcd. 1179.8130; found 1103.785 [M-Ph] + (100%), 1180.834 [M+H] + (30%).
[0060] Example 2:
[0061] Reaction conditions, operation steps and post-treatment for the reaction with monosubstituted star azine molecule 5-CHO-Th-NSA-1 as the main product:
[0062] Into a 100 ml round bottom flask, 108 mg (0.1 mmol) of 5-Br-NSA, 32 mg (0.2 mmol) of 5-CHO-Thiopheneboronic acid, 30 ml of anhydrous toluene, 10 ml of anhydrous ethanol, 10 ml of 2M potassium carbonate solution were added. The condenser was connected and the flask was sealed. Then the flask was frozen in liquid nitrogen until the liquid was completely solidified. The oxygen in the flask was removed by vacuum for several minutes. The flask was filled with argon and thawed in ethanol. The above steps were repeated three times. Then 3.5 mg of tetrakis(triphenylphosphine)palladium was quickly added. The oxygen in the flask was removed by vacuum again. The flask was heated and stirred at 85°C for 12 hours under argon protection. After the reaction was completed, there was a blue-black precipitate at the bottom of the flask, and the upper layer was a yellow-green transparent solution. The product was transferred to a separatory funnel and extracted with dichloromethane and water three times. The organic phase was collected and rotary evaporated. A small amount of dichloromethane was used to dissolve the product, which was then separated and purified by silica gel column chromatography. DCM:PE = 1:1 mixed solvent was used as the developing agent. A yellow solid was obtained. The yellow solid was recrystallized with dichloromethane and methanol. After suction filtration, a yellow crystal was obtained. The yellow-green crystal was confirmed as the final product 5-CHO-Th-NSA-1 by nuclear magnetic resonance and mass spectrometry. The yield was about 40%. By increasing the polarity of the developing agent, a small amount of 5-CHO-Th-NSA-2 was obtained using DCM:PE = 3:1 as the developing agent. No product was obtained using THF:PE = 2:1 as the developing agent. 1 H NMR (500 MHz, DMSO-d6) δ 9.84 (s, 1H), 8.15 (dd, J = 8.8, 2.4 Hz, 1H), 7.96 (d, J = 4.0 Hz, 1H), 7.77 - 7.69 (m, 3H), 7.62 - 7.57 (m, 2H), 7.45 (d, J = 4.0 Hz, 1H), 7.39 - 7.31 (m, 12H), 7.25 - 7.13 (m, 18H), 6.97 - 6.88 (m, 2H), 6.22 (dt, J = 8.5, 2.3 Hz, 3H). MALDI-TOF MS: calcd. 959.5530; found 883.413 [M-Ph] + (100%), 960.554 [M+H] + (40%).
[0063] Example 3:
[0064] Reaction conditions, operation steps and post-treatment of the double-substituted star azine molecule 5-CHO-Th-NSA-2 as the main product:
[0065] In a 100 ml round bottom flask, 108 mg (0.1 mmol) of 5-Br-NSA, 78 mg (0.5 mmol) of 5-CHO-2-thiopheneboronic acid, 30 ml of anhydrous toluene, 10 ml of anhydrous ethanol, 10 ml of 2M potassium carbonate solution were added, and the condenser was connected and sealed. Then the round bottom flask was frozen in liquid nitrogen until the liquid was completely frozen, and the oxygen in the bottle was removed by pumping for several minutes, then argon was introduced into the bottle, and the round bottom flask was placed in ethanol for thawing. Repeat the above steps three times, then open the device, quickly add 3.5 mg of tetrakis(triphenylphosphine)palladium, and repeat the air exchange step once. Heat and stir at 85°C for 12h under argon protection. After the reaction is completed, there is a blue-black precipitate at the bottom of the round bottom flask, and the upper layer is a yellow-green transparent solution. The product was transferred to a separatory funnel and extracted with dichloromethane and water, repeated 3 times, the organic phase was collected and rotary evaporated, then dissolved in a small amount of dichloromethane and separated and purified by silica gel column chromatography, using a mixture of DCM:PE=3:1 as the developing agent, to obtain a yellow-green solid. Recrystallize using dichloromethane as a good solvent and methanol, filter and get a yellow-green crystal, which is confirmed by nuclear magnetic resonance and mass spectrometry to be the final product 5-CHO-Th-NSA-2, with a yield of about 30%. Increase the polarity of the developing agent, and use THF:PE=2:1 as the developing agent to obtain a small amount of 5-CHO-Th-NSA-3. 1 H NMR (400 MHz, DMSO-d6) δ 9.84 (s, 2H), 8.18 (ddd, J = 8.8, 3.8, 2.4 Hz, 2H), 7.96 (dd, J = 4.0, 1.0 Hz, 2H), 7.81 - 7.72 (m, 3H), 7.62 (dd, J = 6.3, 1.8 Hz, 1H), 7.46 (dd, J = 4.0, 1.2 Hz, 2H), 7.40 - 7.31 (m, 12H), 7.28 - 7.15 (m, 18H), 6.29 - 6.19 (m, 3H). MALDI-TOF MS: calcd. 1069.6830; found 993.584 [M-Ph] + (100%), 1070.708 [M+H] + (30%).
[0066] Example 4:
[0067] Reaction conditions, operation steps and post-treatment of the trisubstituted star azine molecule 5-CHO-Th-NSA-3 as the main product:
[0068] In a 100ml flask, 108mg (0.1mmol) 5-Br-NSA, 110mg (0.7mmol) 5- aldehyde-2-thiopheneboronic acid, 30ml dry toluene, 1g potassium carbonate were added, and the condenser was connected and sealed. Then the flask was frozen in liquid nitrogen until the liquid was completely solidified, and the oxygen in the bottle was removed by pumping for several minutes, and then argon was introduced into the bottle, and the flask was placed in ethanol for thawing. After repeating the above steps three times, open the device, quickly add 3.5mg tetrakis(triphenylphosphine)palladium, and repeat the air exchange step once. Heat and stir the reaction at 110°C under argon for 12h. After the reaction was completed, the solution in the bottle was yellow. The product was transferred to a separatory funnel and extracted with dichloromethane and water, repeated 3 times, the organic phase was collected and rotary evaporated, then dissolved in a small amount of dichloromethane and separated and purified by silica gel column chromatography, using THF:PE = 2:1 mixed solvent as developing agent, yellow solid was obtained. Recrystallized with dichloromethane and methanol, filtered and dried to obtain yellow crystals, which were confirmed by nuclear magnetic resonance and mass spectrometry to be the final product 5-CHO-Th-NSA-3, with a yield of about 60%. 1 H NMR (400 MHz, DMSO-d6) δ 9.84 (s, 3H), 8.21 (dd, J = 8.9, 2.4 Hz, 3H), 7.97 (d, J = 4.0 Hz, 3H), 7.80 (d, J = 2.4 Hz, 3H), 7.48 (d, J = 4.0 Hz, 3H), 7.41 - 7.35 (m, 12H), 7.26 - 7.16 (m, 18H), 6.25 (d, J = 8.8 Hz, 3H). MALDI-TOF MS: calcd. 1179.8130; found 1103.785 [M-Ph] + (100%), 1180.834 [M+H] + (30%).
[0069] The above examples are the preferred embodiments of the present application, but the embodiments of the present application are not limited to the above examples, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application shall be equivalent replacement methods, and shall be within the scope of protection of the present application.
Claims
1. A method of synthesizing an asymmetrically substituted reaction intermediate, characterized in that, The one-pot synthesis of the controlled asymmetric substitution of bromo star-shaped azine molecules with 5-aldehyde-2-thiophene boronic acid is carried out in a mixed solvent of toluene, ethanol and water, the volume ratio of toluene, ethanol and water is 3:1:1, the reaction temperature is 80-110℃, the reaction time is 12-24 hours, the feeding amount of 5-aldehyde-2-thiophene boronic acid is 2-8 times of the equivalent of bromo star-shaped azine molecules, and the palladium catalyst is tetra(triphenylphosphine)palladium, the amount of which is 3% of the molar amount of bromo star-shaped azine molecules, to obtain star-shaped azine molecule intermediates which are monosubstituted, disubstituted or trisubstituted with aldehyde thiophenyl groups; the synthesis route is as follows: 。 2. The method of synthesizing asymmetrically substituted reaction intermediates of claim 1, wherein, The method comprises the following steps: adding a star-shaped azine molecule with triple rotational axis symmetry, 5-aldehyde-2-thiophene boronic acid, potassium carbonate and a solvent into a reaction container, connecting a condenser, adding a palladium catalyst under an inert atmosphere, and then heating the reaction container in an oil bath to carry out the reaction, thereby obtaining three intermediates: star-shaped azine molecule intermediates which are monosubstituted, disubstituted and trisubstituted with aldehyde thiophenyl groups.
3. The method of synthesizing asymmetrically substituted reaction intermediates of claim 1, wherein, The temperature of the reaction is 85℃, and the feeding amount of 5-aldehyde-2-thiophene boronic acid is 3-3.3 times of the equivalent of the star-shaped azine molecule with triple rotational axis symmetry.
4. The method for synthesizing an asymmetric substitution reaction intermediate according to claim 1, characterized in that, The temperature of the reaction is 80-85℃, and the feeding amount of 5-aldehyde-2-thiophene boronic acid is 2-2.5 times of the equivalent of the star-shaped azine molecule with triple rotational axis symmetry.
5. The method of synthesizing asymmetrically substituted reaction intermediates of claim 1, wherein, The temperature of the reaction is 85-100℃, and the feeding amount of 5-aldehyde-2-thiophene boronic acid is 4-6 times of the equivalent of the star-shaped azine molecule with triple rotational axis symmetry.
6. The method of synthesizing asymmetrically substituted reaction intermediates of claim 1, wherein, The temperature of the reaction is 110℃, and the feeding amount of 5-aldehyde-2-thiophene boronic acid is 7-8 times of the equivalent of the star-shaped azine molecule with triple rotational axis symmetry.