Stepped bridged ring compound as well as preparation method and application thereof

Abstract

The invention provides a stepped bridged ring compound and a preparation method and application thereof, tetra-alkyne compounds and 6, 13-bis (triisopropyl silyl ethynyl) pentacene react to obtain the stepped bridged ring compound, the preparation method is simple and efficient, a catalyst is not needed, high yield can be obtained by controlling the reaction temperature, and the preparation method is mild, simple and green. The synthesized stepped bridged ring compound has high atom economy, and the Abs of the product can reach 2.0 or above in the interval of 250 nm to 350 nm, which shows that the absorbance of the substance is good, and the substance can be well used for preparation of optical materials.

Description

Technical Field

[0001] The invention relates to the technical field of organic compound synthesis, and in particular to a ladder-type bridged ring compound and a preparation method and application thereof. Background Art

[0002] Aromatic hydrocarbons offer great potential for the diversification of benzene ring compounds, which have different application prospects in chiral ligands / catalysts, precursors / monomers, materials and functional systems, and molecular devices. However, obtaining these high-energy intermediates requires the synthesis of precursors, which involves harsh conditions or multi-step syntheses. It is necessary to develop methods to obtain aromatic hydrocarbons and their related derivatives using simpler substrates and milder conditions.

[0003] As hole transport materials in organic photoluminescent devices, bridged compounds help improve the photoelectric conversion efficiency of the device and extend its service life. In the pharmaceutical field, bridged compounds can regulate the activity of farnesoid X receptor (FXR) and are used to treat diseases mediated by FXR, such as cognitive disorders, psychotic disorders, neurotransmitter-mediated disorders, and neuronal disorders. Bridged compounds are also widely present in nature and usually have important physiological activities, such as the famous anticancer drug paclitaxel and the antimalarial drug artemisinin. In summary, bridged compounds have a wide range of applications in organic electronic devices, drug synthesis, and the treatment of specific diseases.

[0004] As an important skeleton, bridged benzoheterocycles are widely present in many natural products and bioactive molecules, attracting more and more attention from chemists. However, the development of these valuable bridged ring systems is limited by many problems in synthesis, such as the need for pre-modification of substrates, lengthy synthesis steps, and poor atom economy. How to efficiently construct bridged ring systems and synthesize complex bridged ring natural products still faces challenges.

[0005] Bridged ring compounds are widely used, and ladder-type bridged ring compounds with multiple bridged rings will surely be used in more fields. Therefore, the obtained ladder-type bridged ring compounds have good development prospects. Summary of the invention

[0006] The purpose of the present invention is to provide a step-type bridged ring compound and a preparation method thereof. A tetrayne compound is reacted with 6,13-bis(triisopropylsilylethynyl)pentacene to obtain a step-type bridged ring compound. The preparation method is simple and efficient, and a high yield can be obtained by controlling the reaction temperature without a catalyst. The preparation method is mild, simple and green.

[0007] Another object of the present invention is to provide an application of a ladder-type bridged ring compound for use in optical materials. The prepared ladder-type bridged ring compound has an Abs of more than 2.0 in the range of 250nm to 350nm, indicating that the substance has good absorbance and can be well used in the preparation of optical materials.

[0008] The specific technical solutions of the present invention are as follows:

[0009] A method for preparing a ladder-type bridged ring compound, specifically comprising:

[0010] The tetraacene compound and 6,13-bis(triisopropylsilylethynyl)pentacene are mixed in a solvent, heated for reaction, and separated and purified after the reaction to obtain a ladder-type bridged ring compound.

[0011] The molar ratio of the tetraacene compound to 6,13-bis(triisopropylsilylethynyl)pentacene is 2.0-2.2:1;

[0012] The concentration of 6,13-bis(triisopropylsilylethynyl)pentacene in the solvent is 0.2-0.3 mol / L;

[0013] The solvent is selected from toluene;

[0014] The heating reaction refers to reacting at 100-110°C for 6-8h;

[0015] The structural formula of the 6,13-bis(triisopropylsilylethynyl)pentacene is

[0016]

[0017] The separation and purification method comprises the following steps: extracting the crude product with a saturated sodium chloride aqueous solution and ethyl acetate, collecting the organic phase, performing decompression spin drying, wet column loading, and performing column chromatography separation and purification using ethyl acetate: petroleum ether in a volume ratio of 1:20-40 as an eluent to obtain a white solid product, namely, a ladder-type bridged ring compound.

[0018] The tetraacetylene compound has the structural formula E is COOR, R is a straight-chain alkyl group with less than 6 carbon atoms, a branched alkyl group or an unsaturated hydrocarbon, preferably a methyl group; 1 is hydrogen, a straight-chain alkyl group with less than 6 carbon atoms, a branched alkyl group, an ester group, an alkoxy group or a halogen, preferably hydrogen; R 2 It is hydrogen, a straight-chain alkyl group with less than 6 carbon atoms, a branched-chain alkyl group, an ester group, an alkoxy group or a halogen, preferably hydrogen.

[0019] The preparation method of the tetraacetylene compound is:

[0020] 1) Add malonic acid ester and propargyl bromide to anhydrous acetonitrile in an ice-water bath, use sodium hydride as a base, react, and then separate and purify to obtain compound 1;

[0021] 2) Compound 1 prepared in step 1) is mixed with phenylethynyl bromide in a CuCl anhydrous and oxygen-free catalytic system, an aqueous solution of n-butylamine and hydroxylamine hydrochloride are added, the mixture is stirred under ice bath for reaction, and the product is separated and purified to obtain a tetraacetylene compound.

[0022] In step 1), the molar ratio of sodium hydride, malonic acid ester, propargyl bromide and anhydrous acetonitrile is 4-5:1:2.1-2.4:20-23.

[0023] Preferably, the malonate in step 1) is selected from dimethyl malonate or diethyl malonate.

[0024] In step 1), the reaction temperature is 0-5°C under ice-water bath conditions; the reaction time is more than 8 hours; the preferred reaction time is 8.5 hours;

[0025] The separation and purification in step 1) is specifically as follows: the product is washed with a saturated sodium chloride aqueous solution, extracted with ethyl acetate, dried under reduced pressure, and subjected to column chromatography using a mixed solvent of ethyl acetate: petroleum ether in a volume ratio of 1:80 to obtain the product, namely compound 1.

[0026] The structural formula of compound 1 in step 1) is: Where E 1 and E 2 Same as CO 2 R, R is a straight-chain alkyl group, branched-chain alkyl group or unsaturated hydrocarbon with less than six carbon atoms, preferably a methyl group;

[0027] Preferably, the structural formula of compound 1 is:

[0028] In step 2), the molar ratio of the compound 1 in step 1): phenylethynyl bromide: CuCl: hydroxylamine hydrochloride = 1: 2-2.5: 0.15-0.16: 0.07-0.08.

[0029] In step 2), the n-butylamine aqueous solution is used as solvent with a mass concentration of 30%; the hydroxylamine hydrochloride is used as a base to extract hydrogen from the diyne.

[0030] In step 2), the dosage ratio of compound 1 to the aqueous solution of n-butylamine is 0.4-0.5 mol / L;

[0031] In step 2), the stirring reaction time is at least 12 hours;

[0032] In step 2), the preparation method of phenylacetylene bromide is as follows: phenylacetylene and N-bromosuccinimide are reacted in acetone solvent, AgNO 3The reaction was carried out at room temperature for 3 hours under the catalysis of the catalyst, and the crude product was washed with a saturated sodium chloride aqueous solution and extracted with n-hexane to obtain phenylacetylene bromide; wherein phenylacetylene: N-bromosuccinimide and AgNO 3 The molar ratio is 1:1-1.2:0.05.

[0033] In step 2), the separation and purification refers to: washing the product with a saturated sodium chloride solution, extracting with dichloromethane, drying under reduced pressure, and separating by column chromatography with a volume ratio of ethyl acetate: petroleum ether = 1:60-80 to obtain a solid product, i.e., a tetraacetylene compound;

[0034] Preferably, the tetraacetylene compound has the structural formula:

[0035] The present invention provides a ladder-type bridged ring compound, which is prepared by the above-mentioned preparation method; the structural formula of the ladder-type bridged ring compound is:

[0036]

[0037] Wherein, E is COOR, R is a straight-chain alkyl group, a branched alkyl group or an unsaturated hydrocarbon with less than six carbon atoms, preferably a methyl group; 1 is hydrogen, a straight-chain alkyl group with less than 6 carbon atoms, a branched alkyl group, an ester group, an alkoxy group or a halogen, preferably hydrogen; R 2 is hydrogen, a straight-chain alkyl group with less than six carbon atoms, a branched alkyl group, an ester group, an alkoxy group or a halogen, preferably hydrogen; Y is triisopropylsilylethynyl

[0038] The structural formula of the ladder-type bridged ring compound is:

[0039] or

[0040] The invention provides an application of a ladder-type bridged ring compound for optical materials.

[0041] The present invention uses tetraacetylene compounds and 6,13-bis(triisopropylsilylethynyl)pentacene as raw materials, reacts in a toluene solvent at 100-110°C for 6-8h, and under heating conditions, the tetraacetylene itself undergoes HDDA reaction to form a benzyne intermediate, and then the benzyne intermediate undergoes a [4+2] cycloaddition reaction with 6,13-bis(triisopropylsilylethynyl)pentacene to form a ladder-type bridged ring compound. The mechanism diagram is as follows: Fig.11 shown. Fig.11The tetraacetylene compound a undergoes a [4+2] HDDA reaction at high temperature to generate a benzyne compound b. The benzyne compound b reacts with 6,13-bis(triisopropylsilylethynyl)pentacene c in toluene solvent at 110°C for 8 hours. 7 , C 12 With C 5 , C 14 A symmetrical [4+2] cycloaddition reaction occurs at the symmetrical positions, and the terminal carbon atoms of the conjugated system of the benzyne compound b and 6,13-bis(triisopropylsilylethynyl)pentacene c are connected head to tail to form a double six-membered ring transition state compound d. The alkynyl position of the benzyne compound b is rich in electrons and acts as a dienophile. 6,13-bis(triisopropylsilylethynyl)pentacene c acts as a diene, and a [4+2] cycloaddition reaction occurs simultaneously at the symmetrical positions, with the endo addition product being preferentially generated.

[0042] Compared with the prior art, the present invention provides a new method for preparing a ladder-type bridged ring compound to generate a ladder-type bridged ring compound. The synthesized ladder-type bridged ring compound has a high atom economy, and the Abs of the product in the range of 250nm to 350nm can reach more than 2.0, indicating that the substance has good absorbance and can be well used in the preparation of optical materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 It is the general structural formula of a ladder-type bridged ring compound;

[0044] Figure 2 is the structural formula of the ladder-type bridged ring compound prepared in Example 1;

[0045] Figure 3 is the structural formula of the ladder-type bridged ring compound prepared in Example 2;

[0046] Figure 4 is the synthetic reaction formula of the ladder-type bridged ring compound in Example 1;

[0047] Figure 5 is the synthetic reaction formula of the ladder-type bridged ring compound in Example 2;

[0048] Figure 6 The hydrogen nuclear magnetic resonance spectrum of the ladder-type bridged ring compound prepared in Example 1;

[0049] Figure 7 The hydrogen nuclear magnetic resonance spectrum of the ladder-type bridged ring compound prepared in Example 2;

[0050] Figure 8 The carbon NMR spectrum of the ladder-type bridged ring compound prepared in Example 1;

[0051] Fig. 9 The carbon NMR spectrum of the ladder-type bridged ring compound prepared in Example 2;

[0052] Fig.10 The diagram is a mechanism for the preparation of tetrayne compounds;

[0053] Fig.11 is the reaction mechanism diagram of ladder-type bridged ring compound example 1;

[0054] Fig.12 The UV spectrum of the ladder-type bridged ring compound prepared in Example 1;

[0055] Fig.13 The UV spectrum of the ladder-type bridged ring compound prepared in Example 2;

[0056] Fig.14 This is the IUCr structure detection diagram of the ladder-type bridged ring compound prepared in Example 1. DETAILED DESCRIPTION

[0057] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0058] Unless otherwise specified, the test materials and reagents used in the following examples can be obtained from commercial sources.

[0059] If no specific techniques or conditions are specified in the examples, they can be carried out according to the techniques or conditions described in the literature in the art or according to the product instructions.

[0060] Example 1

[0061] A ladder-type bridged ring compound, the structural formula of which is:

[0062]

[0063] The preparation method of the ladder-type bridged ring compound comprises the following steps:

[0064] 1) Using 830mmol sodium hydride as a catalyst, 200mmol dimethyl malonate and 440mmol propargyl bromide were added to 210mL anhydrous acetonitrile, and the mixture was stirred mechanically in an ice-water bath at 0-5°C for 8 hours. The product was washed with a saturated sodium chloride aqueous solution, extracted with ethyl acetate, and dried under reduced pressure. Column chromatography was performed using a mixed solvent of ethyl acetate: petroleum ether in a volume ratio of 1:80 to obtain the product, i.e., compound 1, with the structural formula

[0065]

[0066] 2) Take 100mmol of phenylacetylene and 120mmol of N-bromoacetyl succinimide in a two-necked flask, add an appropriate amount of acetone solvent (the solvent should cover the solid reactant by 0.5cm), add 5mmol of AgNO 3 Catalyzed by a catalyst, the reaction was carried out under magnetic stirring at room temperature for 3 hours. The crude product was washed with a saturated sodium chloride aqueous solution and extracted with n-hexane to obtain phenylacetylene bromide.

[0067] 3) In a 500ml three-necked flask, 40mmol of compound 1 and 0.2g (2.88mmol) of hydroxylamine hydrochloride as a base were mixed in an anhydrous and oxygen-free catalyst system of 0.6g CuCl (6mmol) (a vacuum device for evacuating and releasing argon was used, evacuating first and then releasing, and this was repeated 3 times), and then 100ml of a 30% by mass aqueous solution of n-butylamine (63g water + 27g n-butylamine) was used as a solvent. Half of the solvent was first poured in, and then 90mmol of phenylacetylene bromide prepared in step 3) was poured in, and finally the remaining solvent was poured in. The reaction was carried out under an ice bath with magnetic stirring for 12 hours. The product was washed with a saturated sodium chloride solution and extracted with dichloromethane. The organic phase was collected and dried under reduced pressure. Column chromatography (volume ratio of ethyl acetate: petroleum ether = 1:80) obtained a white solid product, i.e., a tetraacetylene compound, with the structural formula shown in FIG. Figure 4 .

[0068] 4) At 110° C., 2 mmol of the tetrayne compound prepared in step 3) was reacted with 1 mmol of 6,13-bis(triisopropylsilylethynyl)pentacene in 4 mL of toluene for 8 hours. The reaction solution was extracted with a saturated sodium chloride aqueous solution and ethyl acetate, and the organic phase was collected and dried under reduced pressure. The organic phase was loaded onto a column by wet chromatography and separated by column chromatography with a volume ratio of ethyl acetate: petroleum ether = 1:40 to obtain a white solid product, i.e., a ladder-type bridged ring compound, and the column chromatography yield was about 48%.

[0069] The product is a white powder and its structure is shown in Table 1. 1 H NMR, 13 C NMR was used to determine Figure 6 , Figure 8 As shown, the results are as follows:

[0070] 1 H NMR (400 MHz, CDCl 3 )δ7.51-7.45(m,6H),7.43-7.36(m,5H),7.31-7.31(m,1H),7.23-7.17(m,8H),7.15-7.11(m,4H),7.06-7.02(m,4H),6.04-6.03(m,

[0071] 2H),5.94-5.93(m,2H),3.95-3.84(m,4H),3.81-3.78(m,6H),3.75-3.74(m,

[0072] 6H),3.73-3.64(m,4H),1.46-1.40(m,21H),1.02-0.99(m,9H),0.95-0.93(m,

[0073] 9H), 0.67-0.60 (m, 3H);

[0074] 13 C NMR (101 MHz, CDCl 3 )δ172.04,171.79,145.22,144.68,144.16,143.89,

[0075] 141.93,140.44,140.17,138.94,138.44,133.34,131.27,130.88,129.76,128.08,

[0076] 127.85,127.81,127.75,127.03,125.81,125.31,124.05,123.62,123.55,116.06,

[0077] 116.02,114.65,102.14,99.95,98.98,98.48,95.15,87.62,59.39,53.10,53.03,

[0078] 49.74,49.46,41.17,39.25,19.12,19.04,18.66,18.54,11.58,11.41,1.05ppm.

[0079] Optical properties of the ladder-type bridged ring compound prepared above: The ultraviolet spectrum data of the ladder-type bridged ring compound with a concentration of 5.30 mg / ml was measured in an ethanol solvent with a wavelength limit of 235 nm. Fig.12 , Abs in the range of 250nm to 350nm can reach above 2.5, indicating that the absorbance of the substance is good and can be well used in the preparation of optical materials.

[0080] Example 2

[0081] A ladder-type bridged ring compound, the structural formula of which is:

[0082]

[0083] The preparation method of the ladder-type bridged ring compound comprises the following steps:

[0084] 1) Using 830mmol sodium hydride as a catalyst, 200mmol diethyl malonate and 440mmol propargyl bromide were added to 210mL anhydrous acetonitrile, and the mixture was stirred mechanically in an ice-water bath at 0-5°C for 8 hours. The product was washed with a saturated sodium chloride aqueous solution, extracted with ethyl acetate, and dried under reduced pressure. Column chromatography was performed using a mixed solvent of ethyl acetate: petroleum ether in a volume ratio of 1:80 to obtain the product, i.e., compound 1, with the structural formula

[0085]

[0086] 2) Take 100mmol of phenylacetylene and 120mmol of N-bromoacetyl succinimide in a two-necked flask, add an appropriate amount of acetone solvent (the solvent should cover the solid reactant by 0.5cm), add 5mmol of AgNO 3 Catalyzed by a catalyst, the reaction was carried out under magnetic stirring at room temperature for 3 hours. The crude product was washed with a saturated sodium chloride aqueous solution and extracted with n-hexane to obtain phenylacetylene bromide.

[0087] 3) In a 500ml three-necked flask, 40mmol of compound 1 and 0.2g of hydroxylamine hydrochloride as a base were mixed in an anhydrous and oxygen-free catalytic system of 0.6gCuCl (a vacuum device for evacuating and releasing argon was used, evacuating first and then releasing, and this was repeated 3 times), and then 100ml of a 30% by mass aqueous solution of n-butylamine (63g water + 27g n-butylamine) was used as a solvent. Half of the solvent was first poured in, and then 90mmol of phenylacetylene bromide prepared in step 3) was poured in, and finally the remaining solvent was poured in. The reaction was carried out under an ice bath with magnetic stirring for 12 hours. The product was washed with a saturated sodium chloride solution and extracted with dichloromethane. The organic phase was collected and dried under reduced pressure. Column chromatography (volume ratio of ethyl acetate: petroleum ether = 1:80) was performed to obtain a white solid product, i.e., a tetraacetylene compound, with the structural formula shown in FIG. Figure 5 .

[0088] 4) At 110° C., 2 mmol of the tetrayne compound prepared in step 3) was reacted with 1 mmol of 6,13-bis(triisopropylsilylethynyl)pentacene in 4 mL of toluene for 8 hours. The reaction solution was extracted with a saturated sodium chloride aqueous solution and ethyl acetate, and the organic phase was collected and dried under reduced pressure. The organic phase was loaded onto a column by wet chromatography and separated by column chromatography with a volume ratio of ethyl acetate: petroleum ether = 1:40 to obtain a white solid product, i.e., a ladder-type bridged ring compound, and the column chromatography yield was about 42%.

[0089] The product is a white powder and its structure is shown in Table 1. 1 H NMR, 13 C NMR was used to determine Figure 7 , Fig. 9As shown, the results are as follows:

[0090] 1 H NMR (400 MHz, CDCl 3 )δ7.52-7.45(m,6H),7.43-7.34(m,5H),7.31-7.29(m,1H),7.22-7.17(m,8H) ,7.15-7.12(m,4H),7.05-7.01(m,4H),6.04(s,2H),5.93(s,2H),4.26-4.16(m ,8H),3.89-3.81(m,4H),3.74-3.65(m,4H),1.46-1.40(m,21H),1.31-1.23(m ,12H),1.01-0.99(d,J=8Hz,9H),0.94-0.92(d,J=8Hz,9H),0.64-0.60(m,3H);

[0091] 13 C NMR (101 MHz, CDCl 3 )δ171.57,171.27,145.25,144.72,144.16,143.91,141.83,140.41,140.32,138.85,138.4 9,133.52,131.27,130.90,129.79,128.06,127.79,127.71,126.99,125.77,125.26,123.9 9,123.61,116.03,115.99,114.60,102.23,99.97,98.92,98.46,95.03,87.69,61.77,59.6 2,49.75,49.45,41.07,39.09,19.14,19.05,18.65,18.54,14.05,14.01,11.58,11.41ppm.

[0092] The optical properties of the ladder-type bridged ring compound prepared above are measured in an ethanol solvent with a wavelength limit of 235 nm at a concentration of 4.30 mg / ml. Fig.13 , Abs in the range of 250nm to 350nm can reach above 2.0, indicating that the substance has good absorbance and can be well used in the preparation of optical materials.

[0093] The description of the above embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the protection scope of the present invention.

Claims

1. A method for preparing a ladder-type bridged ring compound, characterized in that: The preparation method is specifically: The tetraacene compound and 6,13-bis(triisopropylsilylethynyl)pentacene are mixed in a solvent, heated for reaction, and separated and purified after the reaction to obtain a ladder-type bridged ring compound.

2. The preparation method according to claim 1, characterized in that: The molar ratio of the tetraacene compound to 6,13-bis(triisopropylsilylethynyl)pentacene is 2.0-2.2:

1.

3. The preparation method according to claim 1, characterized in that: The concentration of the 6,13-bis(triisopropylsilylethynyl)pentacene in the solvent is 0.2-0.3 mol / L.

4. The preparation method according to claim 1 or 3, characterized in that: The solvent is selected from toluene.

5. The preparation method according to claim 1, characterized in that: The heating reaction refers to reacting at 100-110° C. for 6-8 hours.

6. The preparation method according to claim 1, characterized in that: The separation and purification method comprises the following steps: extracting the crude product with a saturated sodium chloride aqueous solution and ethyl acetate, collecting the organic phase, performing decompression spin drying, wet column loading, and performing column chromatography separation and purification using ethyl acetate: petroleum ether in a volume ratio of 1:20-40 as an eluent to obtain a white solid product, namely, a ladder-type bridged ring compound.

7. The preparation method according to claim 1 or 3, characterized in that: The tetraacetylene compound has the structural formula E is COOR, R is a straight-chain alkyl group with less than 6 carbon atoms, a branched-chain alkyl group or an unsaturated hydrocarbon; R1 is hydrogen, a straight-chain alkyl group with less than 6 carbon atoms, a branched-chain alkyl group, an ester group, an alkoxy group or a halogen; R2 is hydrogen, a straight-chain alkyl group with less than 6 carbon atoms, a branched-chain alkyl group, an ester group, an alkoxy group or a halogen.

8. A ladder-type bridged ring compound prepared by the preparation method according to any one of claims 1 to 7, characterized in that: The structural formula of the ladder-type bridged ring compound is: Wherein, E is COOR, R is a straight chain alkyl group with less than 6 carbon atoms, a branched chain alkyl group or an unsaturated hydrocarbon; R1 is hydrogen, a straight chain alkyl group with less than 6 carbon atoms, a branched chain alkyl group, an ester group, an alkoxy group or a halogen; R2 is hydrogen, a straight chain alkyl group with less than 6 carbon atoms, a branched chain alkyl group, an ester group, an alkoxy group or a halogen; Y is triisopropylsilylethynyl 9. The ladder-type bridged ring compound according to claim 8, characterized in that: The structural formula of the ladder-type bridged ring compound is: or 10. Use of the ladder-type bridged ring compound according to claim 8 or 9, characterized in that: The ladder-type bridged ring compound is used for optical materials.

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