Multifunctional silanol compound as well as preparation method and application thereof

Abstract

The invention discloses a multifunctional silanol compound and a preparation method and application thereof.The structural formula of the multifunctional silanol compound is shown in the formula (I), and the multifunctional silanol compound is synthesized in the presence of water and a solvent in a catalytic system of a phosphine ligand and a palladium catalyst. The benzo-silacyclobutane compound and alkyne ester can be subjected to intermolecular addition ring-opening reaction and synchronous synthesis to obtain a series of silanol; the compound provided by the invention can be applied to additive products in the organosilicon industry, and the product can be widely used as an intermediate and a formula product; in the field of material science, the polymer can be used for improving surface characteristics of materials, such as improving hydrophilicity or changing adhesion of coatings, or can be used as a polymer modifier. In addition, the coating also has a wide application prospect in the coating industry, medicine and biotechnology. According to the method disclosed by the invention, a chemical selective hydrolysis process is realized, and the multifunctional silanol compound is prepared from silazetane of benzo and an alkyne ester derivative, so that the method has good yield and substrate universality. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the field of organosilanes, and specifically relates to a multifunctional silanol compound and a preparation method and application thereof. Background Art

[0002] As an important silicon-based material, silanol has been widely used in many fields in recent years. As a silicon analog of alcohol, it is a valuable and important compound with wide applications in materials science, synthetic chemistry and medicinal chemistry. Multifunctional silanol compounds are a class of silanol derivatives containing multiple functional groups, which can be alkoxysilyl moieties, acryloxy moieties, epoxide moieties, etc. Due to their diverse functional groups, this type of compound shows a wide range of application potential, especially in synthetic chemistry, medicinal chemistry, materials science and other fields. At present, in terms of the synthesis technology of silanols, the method of hydrolyzing silanes is relatively mature and can efficiently synthesize a variety of silanols. And through chemical modification, researchers can synthesize silanols with specific functions, such as hydrophilic or hydrophobic silanols, to meet specific application requirements. Although there are many synthesis methods, the production cost of some silanols is still high, which limits their competitiveness in large-scale applications. During the synthesis process, problems of inconsistent product performance may occur, especially when the production scale increases, and controlling reaction conditions and product characteristics becomes more complicated. Although many silanols show good biocompatibility, more biosafety assessments are needed to ensure their safety in pharmaceutical and biological applications. Despite their excellent performance, silanols have limited acceptance in some markets, mainly due to the widespread use of traditional materials and their cost advantages.

[0003] In the process of synthesizing silanol products, silicon-containing tetracyclic compounds are usually used as raw materials. This is a class of silicon-containing ring compounds with stable structure but good reactivity. They have a wide range of synthetic uses in synthetic chemistry and functional materials. As the ring strain ability inherent to the small ring system, the ring opening or ring expansion process of silicon-containing tetracyclic rings may occur through the cleavage of silicon-carbon bonds. These organosilicon compounds have unique reactivity and can obtain organosilicon compounds with diverse structures. In this context, silylcyclobutanes (SCBs), including benzosilyl tetracyclic rings (BSCBs), are one of the most important silyl rings and have attracted extensive attention due to their controllable reactivity and Lewis acidity. Therefore, the inherent properties of tetracyclic compounds and the high coordination of organosilicon compounds always provide unexpected possibilities for exploring new transformations of the synthetic value of silylcyclobutanes in constructs. Benzylsilyl tetracyclic rings are also considered to be important tetracyclic rings for the synthesis of a variety of organosilicon compounds with diverse structures because of their strong affinity for Si-C (sp 2 ) and Si-C(sp 3) bonds and the potential for variable chemical selective cleavage. As is known to all, a variety of Si-C (sp 2 ) bond cleavage, including [4+2] cyclization, carbene insertion, and acylsilane ring expansion. However, unlike general silacyclobutanes, transition metal-catalyzed conversions are carried out by Si-C(sp 3 ) bond activation proceeds smoothly, the Si-C (sp 3 ) bonds has proven to be very difficult. Summary of the invention

[0004] The first purpose of the present invention is to provide a multifunctional silanol compound in view of the deficiencies of the prior art. The structure of the present invention is a multifunctional silanol compound constructed with a directing group and different types of steric hindrance and electronic effects. The directing silanol can be used as a coupling reagent for the Hiyama-Denmark reaction, and exhibits the function of the directing group in the C-H functionalization reaction. In addition, organic catalytic reactions can also be achieved by forming hydrogen bonds between the hydroxyl groups in the silanol compound molecules and the substrate. And the directing silanol can be used as an intermediate in drug synthesis, and through later modification and synthetic transformation of functional groups, it is helpful to develop new drugs or improve the synthesis route of existing drugs. The introduction of the directing group of the present invention, and the excellent chemical selectivity to generate complex and diverse silanol compounds, make the present invention have a very broad application prospect in modern chemical synthesis and materials science.

[0005] The present invention is achieved through the following technical solutions:

[0006] A multifunctional silanol compound, the structural formula of which is shown in (I):

[0007]

[0008] R1 is selected from one of hydrogen, monosubstituted halogen atom, C1-10 alkyl, C3-10 cycloalkyl, C1-10 haloalkyl, C1-5 alkoxy, and phenyl;

[0009] R2 is selected from C1-10 alkyl, C3-10 cycloalkyl, C4-10 aryl or substituted phenyl; the substitution is C1-10 alkyl, C1-5 alkoxy, C1-3 haloalkyl, cyano or halogen substitution;

[0010] R3 is selected from C1-10 alkyl, C3-10 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, C4-10 aryl or substituted phenyl; the substitution is C1-10 alkyl, C1-5 alkoxy, C1-3 haloalkyl or halogen substitution;

[0011] R4 is selected from C1-10 alkyl, benzyl, p-toluenesulfonyl, ester or substituted benzyl; the substitution is C1-10 alkyl, C1-5 alkoxy, C1-3 haloalkyl or halogen substitution.

[0012] Preferably, the compound represented by structural formula (I) is selected from one of the compounds represented by the following formulae (Ia) to (Iq).

[0013]

[0014] The second object of the present invention is to provide a method for preparing the above-mentioned multifunctional silanol compound, comprising: reacting a benzosilyl four-membered ring represented by formula (III) by breaking Si-C (sp 3 ) bond with acetylene ester compounds, ring-opening hydrolysis and generation of silanol compounds; the reaction conditions are mild, the reaction is efficient and rapid, the raw materials are cheap and easy to obtain, the obtained product is stable in the air, the yield is high, the product has a single chemical selectivity, and the product is easy to separate and purify.

[0015] The preparation method comprises the following steps:

[0016] Under an inert gas atmosphere, the ligand, palladium catalyst and solvent are pre-stirred for 30 minutes, and then the acetylene ester compound represented by formula (II) and the benzosilane compound represented by formula (III) are added and reacted for 10 hours to 16 hours to obtain a multifunctional silanol compound, wherein the molar ratio of the acetylene ester compound represented by formula (II), the benzosilane compound represented by formula (III), the ligand and the palladium catalyst is 0.9:1:(0.011%-11%):(0.01%-10%); the reaction formula is shown below:

[0017]

[0018] The ligand is selected from one of the following structures:

[0019]

[0020] R=Ph,o-MePh,p-MePh,m-MePh X,Y=O,SiMe 2 ,CH 2 ,CMe 2

[0021]

[0022] Preferably, the palladium catalyst is selected from any one of palladium acetate (II), tris(dibenzylideneacetone)dipalladium (0), (dibenzylideneacetone)palladium (0), allyl(cyclopentadienyl)palladium (II), tris(dibenzylideneacetone)dipalladium, chloroform adduct (0), and the amount used is 5%-10% of the molar amount of the compound represented by the structural formula (II).

[0023] Preferably, the solvent is selected from one or more of alcohols, alkanes, ethers, ketones, aromatic hydrocarbons, and halogenated hydrocarbons. More preferably, the solvent is selected from any one of toluene, tetrahydrofuran, dichloromethane, acetonitrile, n-hexane, dimethyl sulfoxide, or ethylene dichloride.

[0024] Preferably, the reaction temperature is 60-120°C and the reaction time is 10-16h.

[0025] Preferably, after the reaction is completed, a post-treatment step is further included; the post-treatment includes: extraction with ethyl acetate, washing with saturated sodium chloride water, removing the solvent by rotary evaporation, and separating and purifying the crude product by silica gel column chromatography.

[0026] The third object of the present invention is to provide the application of the above-mentioned multifunctional silanol compounds. The compounds of the present invention can be applied to the auxiliary products of the organosilicon industry, and the products can be widely used as intermediates and formulated products, such as as key components in moisture curing sealants. In the field of materials science, it can be used to improve the surface properties of materials, such as improving hydrophilicity or changing the adhesion of coatings, and as a polymer modifier, it is used to improve the performance of plastics, rubbers or fibers. The insulating properties of silanols make them candidates for electronic packaging materials, particularly in applications requiring high temperature stability. In the coating industry, silanols can be used as crosslinking agents or thickeners to improve the durability and adhesion of coatings. In medicine and biotechnology, due to the biocompatibility and chemical stability of silanols, they can be used in the development of drug delivery systems or biomedical materials. And the oxidized forms of its silanols, such as silanols oxidized by peracetic acid, can be used in environmental engineering fields such as water treatment, sterilization and disinfection. The method of the present invention realizes a chemical selective hydrolysis process, and originally adopts benzosilanol and acetylene ester derivatives to prepare multifunctional silanol compounds, and has good yield and substrate universality.

[0027] Specifically, the multifunctional silanol compounds of the present invention can be used for downstream conversion to synthesize new functional silanols. For example, we use LiAlH 4The classical ester partial reduction conversion was carried out, wherein the corresponding silanol IVa containing an additional alcohol group can be obtained in a yield of up to 77%. And silanol IVa can be used for the oxidative synthesis of a novel silanol Va with an aldehyde moiety in a yield of 90%. In addition, the synthetic potential of this Pd-catalyzed benzosilanecyclobutene framework conversion can be further demonstrated in the simple synthesis of silanol IVb containing an acid moiety, which will be an important synthon in the multiple conversion of the acid or silanol group. In addition, the silanol product 7a, which can be further converted into a series of amides IVc containing silanols, can be used as possible building blocks in synthetic chemistry. The structural formula shown in (Ia) can be used for downstream conversions to synthesize novel functionalized silanols:

[0028]

[0029] Therefore, the present invention discloses that the above-mentioned multifunctional silanol compounds have very broad application prospects in modern chemical synthesis and material science.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] (1) The present invention proposes a direct method for catalytic synthesis of novel multifunctional silanols, which achieves unexpected Si-C (sp 3 ) bond activation and addition with acetylene ester compounds, ring-opening hydrolysis to form new silanols. In the method of the present invention, a palladium catalyst and a large sterically hindered phosphine ligand are added to react with acetylene ester compounds and benzo silicon-containing four-membered rings and their derivatives to obtain a series of multifunctional silanols with good yields and a wide range of substrates. The present invention is also successfully used for downstream conversion to synthesize new functionalized silanols. The Pd-catalyzed Si-C (sp 3 ) bond activation, revealing the first example of palladium-catalyzed double Si-C bond activation and its tandem ring expansion and opening transformation in a benzo-containing silanyl tetracyclic ring.

[0032] (2) The present invention realizes the control of single chemical selectivity. At present, the development of new reaction systems for the tandem connection of silicon rings and the activation of double Si-C bonds is lagging behind. In this regard, there is no Si-C (sp) benzo-containing silicon four-membered ring. 3 ) bond activation and its tandem transformation, and the present invention can completely control the chemical selectivity of the reaction in the benzo-containing silicon four-membered ring Si-C (sp 3 ) key to activate.

[0033] (3) The scope of the substrate and the reaction rate of the present invention are greatly improved. By adopting this synthetic route, more diverse substituents can be introduced into the substrate to enrich the substrate structure. At the same time, the presence of the ester group provides the possibility for the introduction of complex drug molecules and functional molecules in the later stage. The reaction can be completed quickly under mild conditions, which is a promising method for the synthesis of benzo-containing silicon-containing four-membered ring Si-C (sp 3 ) key to activate the road and open up a new path. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The crystal structure of compound Iq prepared in Example 21. DETAILED DESCRIPTION

[0035] The present invention is further described below in conjunction with specific examples, but the present invention is not limited to the following examples. Unless otherwise specified, the raw materials used in the examples can be purchased from the market or prepared by conventional methods.

[0036] In the present invention, the alkynyl ester compounds are preferably prepared by the following method. It should be noted that in the following method, R 1 , R 2 , R 3 , R 4 etc. are all as defined in the present invention.

[0037] Example 1: General method for preparing the compound represented by formula (II)

[0038]

[0039] In a 25 mL Shrek tube, 2 mol% of palladium catalyst and 1.5 mol% of cuprous iodide were added, followed by S2 and tetrahydrofuran as solvent. Deoxygenation was performed for 2 minutes, followed by the addition of triethylamine (3.0 equivalents) and S1, and the mixture was stirred at room temperature for 12 hours to obtain compound II.

[0040] Example 2: General method for preparing the compound represented by formula (III)

[0041]

[0042] The ether solution containing S3 (1.0 eq.) and S4 (1.2 eq.) was added dropwise to the ether solution of magnesium (3.1 eq.). The reaction mixture was refluxed for 24 h, then cooled to room temperature and treated with saturated aqueous ammonium chloride. The mixture was extracted three times with ethyl acetate. The combined organic phases were then washed with water and brine and washed with anhydrous Na 2 SO 4 The residue was purified by silica gel column chromatography to obtain compound III.

[0043] Example 3

[0044] Selective Si-C (sp 3 ) bond cleavage, olefin migration, and ring-opening hydrolysis to form silanols

[0045] Reaction conditions: (1) Under nitrogen atmosphere, the compound represented by formula (II) (0.18 mmol), the compound represented by formula (III) (0.2 mmol), 10 mol% Pd / ligand (1:1.1), 2 mL dimethyl sulfoxide, H 2 O (0.18 mmol) was reacted overnight; wherein the ligand is selected from L1 to L10;

[0046]

[0047] The construction of multifunctional chiral silanol 7a was studied using benzosilyl tetracyclic ring 1a. 2 As the optimal catalyst, L10 as the optimal ligand, DMSO as the optimal solvent, the reaction was completed at 120°C for 16 hours, and a yield of 50% was obtained.

[0048] Example 4

[0049] General method for preparing the compound represented by formula (I):

[0050] Pd(OAc)2 (10 mol%, 4.5 mg 0.02 mmol), Xantphos (i.e., ligand L10) (11 mol%, 12.73 mg 0.022 mmol) were added to a dry 25 mL Schlenk tube equipped with a magnetic stirring bar, which was evacuated and backfilled with N2. Solvent DMSO (2 mL) was added to the mixture under N2. The mixture was then stirred at room temperature for 30 minutes. Subsequently, formula (II) (0.9 eq, 0.18 mmol) and formula (III) (1.0 eq, 0.2 mmol) were added to the reaction mixture, and the reactants were stirred at 120°C for 16 h. After the reaction was completed, the mixture was cooled to room temperature. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed with water and brine, and washed with anhydrous Na 2 SO 4 After removal of the solvent under reduced pressure, the residue was purified by column chromatography on silica gel (PE / EA) to give the product (I).

[0051] Example 5

[0052]

[0053] Preparation of compound Ia: Ia was prepared by the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 33.0 mg of compound Ia with a yield of 50%, as a yellow oil.

[0054] 1 H NMR(400MHz,Chloroform-d)δ7.80(s,1H),7.59(dd,J=7.2,1.2Hz,1H),7.50(dd,J=7.6,1.6Hz,2 H),7.35–7.25(m,5H),7.01(d,J=7.6Hz,1H),3.66(s,3H),3.56(s,3H),3.18(s,2H),0.59(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ173.44,168.02,146.09,141.83,138.36,137.84,136.04,134.69,130.81,130.47,128.6 2,128.45,128.37,127.60,53.26,53.04,33.59,0.00.HRMS(ESI+)m / z:[M+Na]+calculated for C 20 H 22 O 5 NaSi:393.1129,found:393.1123

[0055] Example 6

[0056]

[0057] Preparation of compound Ib: Ib was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 38.0 mg of compound Ib with a yield of 53%, as a yellow oil.

[0058] 1 H NMR(400MHz,Chloroform-d)δ7.80(s,1H),7.60(dd,J=7.6,1.6Hz,1H),7.52(dt,J=5.6,1.6Hz,2H),7.36–7.24(m,5H),7.02(d,J=7. 2Hz,1H),4.12(q,J=7.2Hz,2H),4.03(qd,J=7.2,2.8Hz,2H),3.19(s,2H),1.19(t,J=7.2Hz,3H),1.14(t,J=7.2Hz,3H),0.60(s,3H). 13C NMR (101 MHz, CDCl 3 )δ172.98,167.53,145.49,141.90,138.46,137.88,135.97,134.62,130.71,130.38,128.58,128. 48,128.26,128.01,62.12,61.87,33.89,14.93,14.86,-0.00.HRMS(ESI+)m / z:[M+Na]+calculated for C 22 H 26 O 5 NaSi:421.1442,found:421.1436.

[0059] Example 7

[0060]

[0061] Preparation of compound Ic: Ic was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 42.0 mg of compound Ic with a yield of 55%, as a yellow oil.

[0062] 1 H NMR(400MHz,Chloroform-d)δ7.83(s,1H),7.59(dd,J=7.2,1.6Hz,1H),7.51(dd,J=7.6,1.2Hz,2H),7.35–7.24(m,5H),7.03(d,J=7.2Hz,1H),4.02( t,J=6.4Hz,2H),3.93(td,J=6.8,3.2Hz,2H),3.20(s,2H),1.61–1.55(m,2 H),1.55–1.49(m,2H),0.87–0.83(m,3H),0.83–0.79(m,3H),0.59(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ172.99,167.47,145.44,141.91,138.29,137.72,135.92,134.53,130.65,130.35,128.53,128.42,128 .16,128.09,67.68,67.43,33.78,22.66,22.54,11.19,11.01,-0.00.HRMS(ESI+)m / z:[M+Na]+calculated for C 24 H 30 NaO 5Si:449.1755,found:449.1703

[0063] Example 8

[0064]

[0065] Preparation of compound Id: Id was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 47.5 mg of compound Id with a yield of 62% as a yellow oil.

[0066] 1 H NMR(400MHz,Chloroform-d)δ7.79(s,1H),7.60(dd,J=7.2,1.2Hz,1H),7.55–7.47(m,2H),7.34–7.24(m,5H),7. 02(d,J=7.6Hz,1H),4.99(p,J=6.4Hz,1H),4.88(p,J=6.4Hz,1H),3.15(s,2H),1.18–1.09(m,12H),0.59(s,3H). 13 CNMR (101MHz, CDCl 3 )δ172.50,166.85,145.07,142.06,138.42,137.70,135.84,134.52,130.62,130.30,128.62,128.55,12 8.39,128.06,69.62,69.28,34.09,22.53,22.49,22.39,22.35,0.00HRMS(ESI+)m / z:[M+Na]+calculated for C 24 H 30 NaO 5 Si:449.1755,found:449.1724

[0067] Example 9

[0068]

[0069] Preparation of compound Ie: Ie was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 37.6 mg of compound Ie with a yield of 40%, as a yellow oil.

[0070] 1H NMR(400MHz,Chloroform-d)δ7.90(s,1H),7.59(dd,J=6.8,1.6Hz,1H),7.48–7.44(m,2H),7.32 –7.19(m,15H),7.00(d,J=7.2Hz,1H),5.15–5.06(m,2H),4.96(s,2H),3.26(s,2H),0.58(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ145.39,144.14,140.94,135.77,134.25,133.86,129.70,128.55,127.60,127.0 5,126.45,65.11,31.59,30.21,29.79,-0.72.HRMS(ESI+)m / z:[M+Na]+calculated for C 32 H 30 NaO 5 Si:545.1755,found:545.1747.

[0071] Example 10

[0072]

[0073] Preparation of compound If: If was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 27.2 mg of compound If with a yield of 45%, as a yellow oil.

[0074] 1 H NMR(400MHz,Chloroform-d)δ8.14(s,1H),7.53(dd,J=7.2,1.6Hz,1H),7.35–7.25(m,2H),7.07 (d,J=7.6Hz,1H),3.76(s,3H),3.59(s,3H),3.30(s,2H),0.92–0.88(m,5H),0.83–0.76(m,5H). 13 C NMR (101 MHz, CDCl 3 )δ172.30,167.45,145.50,140.86,136.91,134.86,129.53,127.82,127.51, 126.46,52.44,52.36,32.90,6.78,6.64.HRMS(ESI+)m / z:[M+Na]+calculated for C 17 H 24NaO 5 Si:359.1285,found:359.1280.

[0075] Embodiment 11

[0076]

[0077] Preparation of compound Ig: Ig was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 28.6 mg of compound Ig with a yield of 42%, as a yellow oil.

[0078] 1 H NMR (400MHz, Chloroform-d) δ8.05(s,1H),7.53(dd,J=7.2,1.2Hz,1H),7.31(td,J=7.2,1.2Hz,1H),7.23(t,J=7.6Hz,1H),7.16(d ,J=7.6Hz,1H),3.67(d,J=2.8Hz,3H),3.66–3.61(m,3H),3.26(s,2H),1.18–1.04(m,8H),0.79–0.70(m,5H),0.28(d,J=5.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ171.79,167.58,144.14,140.17,138.61,134.70,129.60,128.33,127.88,126.23, 52.23,33.50,33.17,31.56,23.23,22.67,17.99,14.22,0.09,-0.00.HRMS(ESI+)m / z:[M+H]+calculated for C 20 H 31 O 5 Si:379.1935,found:379.1940.

[0079] Example 12

[0080]

[0081] Preparation of compound Ih: Ih was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 40.9 mg of compound Ih with a yield of 50%, as a yellow oil.

[0082] 1H NMR(400MHz,Chloroform-d)δ7.86(s,1H),7.59(dd,J=7.6,1.6Hz,1H),7.49-7.47(m,2H),7.33–7.22(m,5H),7.06–7.02(m,1 H),3.84(dd,J=6.8,2.4Hz,2H),3.74(dd,J=6.4,3.6Hz,2H),3.19(s,2H),1.86-1.76(m,2H),0.84–0.78(m,12H),0.58(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ172.84,167.38,145.34,141.83,138.16,137.66,135.89,134.47,130.58,130.31,128.48,128.41,128.13,12 7.97,72.10,71.88,33.74,28.38,28.24,19.80,19.78,19.74,19.66,-0.00.HRMS(ESI+)m / z:[M+Na]+calculated for C 26 H 34 NaO 5 Si:447.2068,found:447.2049.

[0083] Embodiment 13

[0084]

[0085] Preparation of compound Ii: Ii was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 29.5 mg of compound Ii with a yield of 45%, as a yellow oil.

[0086] 1 H NMR(400MHz,Chloroform-d)δ8.13(s,1H),7.53(dd,J=7.2,1.6Hz,1H),7.33–7.24(m,2H),7.06(d,J=7. 6Hz,1H),3.76(s,3H),3.60(s,3H),3.30(s,2H),0.88(t,J=7.2Hz,6H),0.82–0.71(m,5H),-0.00(s,3H). 13 C NMR (101 MHz, CDCl 3)δ171.23,166.41,144.47,139.65,136.52,133.68,128.42,126.76,126.49,125.32, 51.38,51.31,31.86,17.18,17.14,15.57,0.00.HRMS(ESI+)m / z:[M+Na]+calculated for C 19 H 28 NaO 5 Si:387.1598,found:387.1577.

[0087] Embodiment 14

[0088]

[0089] Preparation of compound Ij: Ij was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 45.8 mg of compound Ij with a yield of 56%, as a yellow oil.

[0090] 1 H NMR(400MHz,Chloroform-d)δ7.82(t,J=3.2Hz,1H),7.59(dq,J=7.6,1.6Hz,1H),7.53–7.50(m,2H),7.34–7.26(m,5H),7.04(d ,J=7.2Hz,1H),4.87–4.79(m,1H),4.76–4.70(m,1H),3.18(s,2H),1.19–1.03(m,8H),0.85–0.72(m,8H),0.60(d,J=1.2Hz,3H). 13 CNMR (101MHz, CDCl 3 )δ171.96,166.31,144.31,141.38,135.17,133.82,129.93,129.62,127.92,127.86,127.68,127.37,73.53,73 .11,33.33,31.96,29.74,29.41,28.81,22.74,19.23,14.19,9.64,-0.64.HRMS(ESI+)m / z:[M+Na]+calculated for C 26 H 34 NaO 5 Si:477.2068,found:477.2052.

[0091] Embodiment 15

[0092]

[0093] Preparation of compound Ik: Ik was prepared according to the same method as in Example 4. The reaction conditions and other parameters were the same as in Example 4 to obtain 32 mg of compound Ik with a yield of 46%, as a yellow oil.

[0094] 1 H NMR(400MHz,Chloroform-d)δ7.72(s,1H),7.57(d,J=1.6Hz,1H),7.47(dd,J=7.6, 1.2Hz,2H),7.32–7.25(m,5H),3.65(s,3H),3.58(s,3H),3.16(s,2H),0.57(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ173.18,167.64,144.60,142.98,138.32,138.24,138.06,134.59,130 .73,130.55,128.63,128.55,128.32,128.03,53.31,53.09,33.52,0.00. 19 FNMR (471MHz, CDCl 3 )δ-110.08.HRMS(ESI+)m / z:[M+Na]+calculated for C 20 H 21 FNaO 5 Si:411.1034,found:411.1023.

[0095] Example 16

[0096]

[0097] Preparation of compound Il: Il was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 23 mg of compound Il with a yield of 40%, as a yellow oil.

[0098] 1H NMR(400MHz,Chloroform-d)δ8.05(s,1H),7.56–7.48(m,1H),7.31(td,J=7.6,1.6Hz,1H),7.26–7.21(m,1H),7 .16(d,J=7.6Hz,1H),3.67(d,J=2.8Hz,3H),3.63(s,3H),3.26(s,2H),0.80–0.74(m,5H),0.29(d,J=3.2Hz,3H). 13 CNMR (101MHz, CDCl 3 )δ171.67,167.50,143.99,140.16,138.14,134.67,129.54,128.27,127.76,126 .18,52.19,52.13,33.38,9.51,6.81,-0.68.HRMS(ESI+)m / z:[M+Na]+calculated for C 16 H 22 NaO 5 Si:345.1129,found:345.1125.

[0099] Embodiment 17

[0100]

[0101] Preparation of compound Im: Im was prepared according to the same method as in Example 4. The stoichiometric ratio of reactants, reaction conditions and other parameters were the same as in Example 4 to obtain 31 mg of compound Im with a yield of 45% as a yellow oil.

[0102] 1 H NMR(400MHz,Chloroform-d)δ7.77(s,1H),7.51–7.45(m,3H),7.29–7.22(m,3H),7.08–7.03 (m,1H),6.84–6.79(m,1H),3.63(s,3H),3.54(s,3H),3.17(s,2H),2.24(s,3H),0.54(s,3H). 13 C NMR (101 MHz, CDCl 3)δ173.42,168.05,146.21,141.87,140.78,138.61,136.15,134.65,134.32,130.33,129.13,1 29.08,128.52,127.34,53.18,52.98,33.61,22.24,0.00.HRMS(ESI+)m / z:[M+Na]+calculated for C 21 H 24 NaO 5 Si:407.1285,found:407.1275.

[0103] Embodiment 18

[0104]

[0105] Preparation of compound In: In was prepared according to the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 36.6 mg of In compound with a yield of 53%, as a yellow oil.

[0106] 1 H NMR(400MHz,Chloroform-d)δ7.78(s,1H),7.61(dd,J=7.2,1.6Hz,1H),7.51–7.45(m,2H),7.32–7.22( m,5H),7.03–6.97(m,1H),3.62(s,3H),3.54(s,3H),3.16(s,2H),1.09–1.02(m,2H),0.97–0.92(m,3H). 13 C NMR (101 MHz, CDCl 3 )δ172.60,167.25,145.38,141.21,136.63,136.31,135.34,134.11,129.93,129.60,127.77, 127.74,127.53,126.61,52.43,52.20,32.80,6.87,6.63.HRMS(ESI+)m / z:[M+Na]+calculated for C 21 H 24 NaO 5 Si:407.1285,found:407.1271.

[0107] Embodiment 19

[0108]

[0109] Preparation of compound Io: Io was prepared by the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 28.6 mg of compound Io with a yield of 40%, as a yellow oil.

[0110] 1 H NMR(400MHz,Chloroform-d)δ7.78(s,1H),7.68–7.64(m,1H),7.50(dt,J=5.6,1.6Hz,2H),7.33–7.23(m, 5H),7.01–6.99(m,1H),3.64(s,3H),3.56(s,3H),3.17(s,2H),1.50–1.41(m,1H),1.00(t,J=7.6Hz,6H). 13 C NMR (101 MHz, CDCl 3 )δ172.67,167.22,145.73,141.46,135.91,135.70,135.40,134.36,129.85,129.52,127.83,127.71 ,127.42,126.47,52.46,52.20,32.74,17.20,16.98,12.93.HRMS(ESI+)m / z:[M+Na]+calculatedfor C 22 H 26 NaO 5 Si:421.1442,found:421.1436.

[0111] Embodiment 20

[0112]

[0113] Preparation of compound Ip: Ip was prepared according to the same method as in Example 4. The stoichiometric ratio of reactants, reaction conditions and other parameters were the same as in Example 4 to obtain 32.5 mg of compound Ip with a yield of 47% as a yellow oil.

[0114] 1 H NMR(400MHz,Chloroform-d)δ7.77(s,1H),7.52–7.47(m,2H),7.42(d,J=2Hz,1H),7.31–7.25(m,3H),7.13 (dd,J=8,1.8Hz,1H),6.91(d,J=8Hz,1H),3.64(s,3H),3.56(s,3H),3.19(s,2H),2.27(s,3H),0.57(s,3H). 13 C NMR (101 MHz, CDCl3 )δ173.42,168.12,146.14,138.82,138.46,138.06,137.71,136.72,134.66,131.45,130.42,12 8.58,128.50,127.16,53.18,52.95,33.58,22.18,1.84,-0.00.HRMS(ESI+)m / z:[M]+calculated forC 21 H 24 O 5 Si:384.1393,found:384.1009.

[0115] Embodiment 21

[0116]

[0117] Preparation of compound Iq: Iq was prepared by the same method as in Example 4, with the same parameters as in Example 4 such as the stoichiometric ratio of reactants and reaction conditions, to obtain 38.9 mg of compound Iq with a yield of 50%, as a yellow solid with a melting point of 124-127°C.

[0118] 1 H NMR(400MHz,Chloroform-d)δ7.69(s,1H),7.60–7.54(m,4H),7.39(dd,J=7.6,1.6Hz, 1H),7.34–7.26(m,7H),7.02(d,J=7.6Hz,1H),3.56(s,3H),3.54(s,3H),3.17(s,2H). 13 C NMR (101 MHz, CDCl 3 )δ172.88,167.07,145.55,141.67,136.75,135.69,135.33,134.85,130.25,129.94,12 7.90,127.68,127.46,126.84,52.56,52.11,32.80.HRMS(ESI+)m / z:[M+Na]+calculated for C 25 H 24 NaO 5 Si:455.1285,found:455.1277.

[0119] The configuration of compound Iq was determined by X-ray single crystal diffraction.

[0120] Compound Iq was precipitated in a culture system of dichloromethane and n-hexane, and the X-ray crystal structure data was deposited in the Cambridge Crystallographic Data Center with the number CCDC2368448. Figure 1 The detailed information is shown in Table 2 below.

[0121] Table 2 Compound Iq crystal information

[0122]

[0123]

[0124] Example 22: Late conversion of the compound shown in (Ia)

[0125] General method for preparing compound (IVa)

[0126]

[0127] Preparation of compound Iva: A 50 mL round bottom flask was charged with a magnetic stirring bar, 370 (1 mmol, 1 eq.), and 10 mL of THF. After cooling to 0°C, 76 mg (2 mmol, 2 eq.) of lithium aluminum hydride was added. The reaction mixture was then stirred for 10 minutes, and then the cold bath was removed. The mixture was then heated to reflux for 12 hours. After the reaction mixture was cooled to 0°C, 5 mL of saturated aqueous ammonium sulfate solution was slowly added to the mixture, followed by 5 mL of 2.5 M NaOH (aqueous solution) and 5 mL of saturated Rochelle salt. After stirring for 3 hours, the product was extracted from the mixture with ethyl acetate, and then with Na 2 SO 4 Drying gave product IVa in 77% yield.

[0128] 1 H NMR(400MHz,Chloroform-d)δ7.44–7.11(m,9H),6.74(s,1H),4.07–3.94(m,4 H),2.28(s,1H),1.97(s,1H),1.44(s,1H),1.18(t,J=7.2Hz,1H),0.50(s,3H). 13 C NMR (101 MHz, CDCl 3 )δ143.78,139.61,137.01,136.14,134.81,130.71,130.53,129.81,128.88,127.42,67.12,62.27,32.33,-0.00.HRMS(ESI+)m / z:[M+Na]+calculated forC 18 H 22 NaO3 Si:337.123,found:337.1196.

[0129] Embodiment 23

[0130]

[0131] Preparation of compound Va: Add 242 mg (0.77 mmol, 1.0 eq) of IVa to a 50 mL round bottom flask equipped with a magnetic stir bar, then add 10 mL of dimethyl sulfoxide. After adding 240 mg (0.85 mmol, 1.1 eq) of IBX, stir the suspension for 3 hours, then add 10 mL of deionized water at 0°C. Then filter the suspension and wash with 20 mL portions of CH 2 Cl 2 The filtered suspension was washed four times. The combined organic volume was then washed with three 50 mL portions of deionized water. The organic mixture was then passed directly through Na 2 SO 4 Filtration and concentration gave product Va with a yield of 90%.

[0132] 1 H NMR(400MHz,Chloroform-d)δ9.23(s,1H),7.61(d,J=6.8Hz,1H),7.49(d,J=7.2Hz,2H),7.31(dd,J=12.4 ,10.8Hz,6H),7.11(d,J=7.6Hz,1H),3.52(m,2H),2.47(t,J=5.9Hz,2H),2.01–1.88(m,1H),0.57(s,3H). 13 C NMR (101MHz, CDCl3) δ196.64,155.66,141.79,140.90,138.32,137.40,135.96,134.42,134.34,134. 19,130.72,130.57,130.57,128.72,128.49,61.36,27.97,-0.00.HRMS(ESI+)m / z:[M+H]+calculated for C 18 H 21 O 3 Si:313.1254,found:313.1223.

[0133] Embodiment 24

[0134]

[0135] Preparation of compound IVb: Ia was dissolved in MeOH-H2O (8 mL, MeOH:H2O=3:1) and slowly added to 167 mg (7 mmol, 8.75 eq) LiOH at 0°C. The reaction mixture was then heated to room temperature overnight. Methanol was removed by vacuum evaporation, and the residual aqueous solution was partitioned with EA (20 mL). The organic phase was extracted twice with H2O, and the combined aqueous extracts were acidified to pH=2 with 1N HCl. The aqueous phase was extracted 3 times with CHCl3, and the combined organic extracts were dried over Na2SO4 and concentrated to give product IVb with a yield of 90%.

[0136] 1 H NMR (400MHz, DMSO-d6) δ7.93(d,J=4.4Hz,1H),7.63(t,J=7.6Hz,1H),7.51–7.42(m,2H),7.38–7.09(m,7H),5.21(s,1H),3.08(s,2H),0.53(s,3H). 13 C NMR (101MHz, DMSO) δ173.35,168.75,141.22,135.20,135.17,133.93,133.89,129.68,129.44, 128.05,127.98,127.65,127.43,33.46,33.30,21.02,-0.50.HRMS(ESI+)m / z:[M]+calculated forC 18 H 18 O 5 Si:342.0924,found:314.0821.

[0137] Embodiment 25

[0138]

[0139] Preparation of compound IVca: A toluene solution (8 mL) of Ia (0.5 mmol) was added to 117.9 mg (1.1 mmol, 2.2 eq) of 11a and 2 mL (4 mmol, 8.0 eq) of NaHMDS. The reaction mixture was stirred at room temperature overnight and treated with saturated ammonium chloride solution. The mixture was extracted three times with ethyl acetate, and the combined organic phases were washed with water and brine, and then washed with anhydrous Na 2 After removal of the solvent under reduced pressure, the residue was purified by column chromatography on silica gel (PE / EA) to afford the desired product Ivca in 30% yield.

[0140] 1H NMR(400MHz,)δ8.97(s,1H),8.15(s,1H),7.58(d,J=7.2Hz,1H),7.53(d,J=6.8Hz,2H),7.39–7.16(m,11H),7.08(d,J =7.6Hz,1H),7.00(d,J=8.0Hz,2H),6.89(d,J=8.0Hz,2H),3.36–3.12(m,2H),2.22(s,3H),2.16(s,3H),0.57(s,3H). 13 C NMR(101MHz,)δ169.85,169.00,141.44,139.35,138.89,137.08,135.83,135.72,135.56,134.90,134.42,134.15,132.77,130.75, 130.38,129.96,129.78,128.75,128.63,127.97,121.07,120.65,37.13,21.48,21.40,-0.00.HRMS(ESI+)m / z:[M+Na]+calculated for C 32 H 32 N 2 NaO 3 Si:543.2074,found:543.2081.

[0141] Embodiment 26

[0142]

[0143] Preparation of compound IVcb: IVca was prepared according to substantially the same method as in Example 28, with the stoichiometric ratio of reactants, reaction conditions and other parameters being the same as in Example 28, to obtain 116 mg of compound IVcb with a yield of 42%, as a yellow oil.

[0144] 1 H NMR(400MHz,)δ9.09(s,1H),8.21(s,1H),7.62(dd,J=7.2,1.6Hz,1H),7.58–7.55(m,2H),7.41–7.32(m,4H),7.30–7.21(m, 6H),7.11(d,J=7.4Hz,1H),6.82–6.73(m,3H),6.67–6.62(m,2H),3.72(s,3H),3.67(s,3H),3.36–3.20(m,2H),0.60(s,3H). 13C NMR(101MHz,)δ169.81,168.95,157.17,156.81,141.48,139.27,138.97,137.14,135.84,134.15,132.82,131.49,131.20,130.72 ,130.36,128.74,128.64,127.94,122.82,122.34,114.58,114.39,56.00,55.94,36.91,0.00.HRMS(ESI+)m / z:[M+Na]+calculated forC 32 H 32 N 2 NaO 5 Si:575.1973,found:575.1988.

[0145] Embodiment 27

[0146]

[0147] Preparation of compound IVcc: IVca was prepared according to substantially the same method as in Example 28, with the stoichiometric ratio of reactants, reaction conditions and other parameters being the same as in Example 28, to obtain 81 mg of compound IVcc with a yield of 33%, as a yellow oil.

[0148] 1 H NMR(400MHz,)δ9.15–9.03(m,1H),8.35(d,J=5.6Hz,1H),7.57(d,J=7.2Hz,1H),7.52(d,J=7.2Hz,2H),7.41(d,J=8.0Hz,3H),7.35– 7.31(m,3H),7.26–7.16(m,6H),7.09(d,J=7.6Hz,3H),7.02(t,J=7.6Hz,2H),6.94(d,J=7.6Hz,2H),3.35–3.16(m,2H),0.58(s,3H). 13 C NMR(101MHz,)δ170.01,169.19,141.29,139.67,138.67,138.25,138.15,137.07,135.84,134.14,132.49,130.75,130.41,129.4 6,129.42,129.30,128.74,128.63,128.03,125.24,124.87,120.96,120.58,37.13,0.00.HRMS(ESI+)m / z:[M+Na]+calculatedfor C 30 H28 N 2 NaO 3 Si:515.1761,found:515.1758.

[0149] Embodiment 28

[0150]

[0151] Preparation of compound IVcd: IVca was prepared according to substantially the same method as in Example 28, with the stoichiometric ratio of reactants, reaction conditions and other parameters being the same as in Example 28, to obtain 59 mg of compound IVcd with a yield of 23%, as a yellow oil.

[0152] 1 H NMR(400MHz,)δ7.91(s,1H),7.67(d,J=7.2Hz,1H),7.56–7.53(m,1H),7.50–7. 46(m,3H),7.41–7.22(m,19H),4.65(s,2H),3.22(t,J=3.2Hz,2H),0.67(s,3H). 13 C NMR(101MHz,)δ173.85,170.42,136.06,135.79,133.77,130.20,129.93,128.98,128.71,128.68 ,128.01,127.93,127.88,124.51,42.42,33.53,29.73,-0.26.HRMS(ESI+)m / z:[M+H]+calculated for C 32 H 33 N 2 O 3 Si:521.2255.,found:521.2204.

[0153] Embodiment 29

[0154]

[0155] Preparation of compound IVce: IVca was prepared according to substantially the same method as in Example 28, with the stoichiometric ratio of reactants, reaction conditions and other parameters being the same as in Example 28, to obtain 82 mg of compound IVce with a yield of 30%, as a yellow oil.

[0156] 1H NMR(400MHz,)δ7.88(d,J=2.4Hz,1H),7.65(dd,J=7.2,1.2Hz,1H),7.53–7.47(m,2H),7.41–7.11(m ,14H),3.73–3.66(m,2H),3.20(t,J=2.8Hz,2H),2.84–2.77(m,2H),1.21–1.14(m,4H),0.65(s,3H). 13 C NMR(101MHz,)δ174.13,170.79,139.88,139.85,137.99,137.44,136.03,135.96,134.00,130.32,130.11,129.01,128.8 8,128.75,128.13,128.07,126.87,124.48,40.20,33.88,33.63,29.89,1.21,-0.00.HRMS(ESI+)m / z:[M+H]+calculated for C 34 H 37 N 2 O 3 Si:549.2568,found:549.2512.

[0157] The examples in the above specific implementation scheme are illustrative rather than restrictive, and several examples can be cited according to the limited scope. Therefore, any changes and modifications made without departing from the overall concept of the present invention should fall within the scope of protection defined by the present invention.

Claims

1. A multifunctional silanol compound, characterized in that: The structural formula is shown in (I): Among them, R 1 One selected from hydrogen, halogen, C1-10 alkyl, C3-10 cycloalkyl, C1-10 haloalkyl, C1-5 alkoxy, and phenyl; R 2 Selected from C1-10 alkyl, C3-10 cycloalkyl, C4-10 aryl or substituted phenyl; the substitution is C1-10 alkyl, C1-5 alkoxy, C1-3 haloalkyl, cyano or halogen substitution; R 3 Selected from C1-10 alkyl, C3-10 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, C4-10 aryl or substituted phenyl; the substitution is C1-10 alkyl, C1-5 alkoxy, C1-3 haloalkyl or halogen substitution; R 4 Selected from C1-10 alkyl, benzyl, p-toluenesulfonyl, ester group or substituted benzyl; the substitution is C1-10 alkyl, C1-5 alkoxy, C1-3 haloalkyl or halogen substitution.

2. The multifunctional silanol compound according to claim 1, characterized in that: The multifunctional silanol compound is selected from one of the compounds represented by the following formulas (Ia) to (Iq):

3. A method for preparing a multifunctional silanol compound according to any one of claims 1 to 2, characterized in that: The preparation method comprises the following steps: Under an inert gas atmosphere, the ligand, the palladium catalyst and the solvent are pre-stirred, and then the acetylene ester compound represented by formula (II) and the benzosilacyclobutane compound represented by formula (III) are added to react to obtain a multifunctional silanol compound; The molar ratio of the acetylene ester compound represented by formula (II), the benzosilacyclobutane compound represented by formula (III), the ligand, and the palladium catalyst is 0.9:1:(0.011%-11%):(0.01%-10%); Its synthetic route is as follows:

4. The preparation method according to claim 3, characterized in that: The ligand is selected from one of the following structures:

5. The preparation method according to claim 3, characterized in that: The palladium catalyst is selected from one of palladium acetate (II), tris(dibenzylideneacetone)dipalladium (0), (dibenzylideneacetone)palladium (0), allyl(cyclopentadienyl)palladium (II), tris(dibenzylideneacetone)dipalladium, and chloroform adduct (0).

6. The preparation method according to claim 3, characterized in that: The solvent is selected from toluene, tetrahydrofuran, dichloromethane, acetonitrile, n-hexane, dimethyl sulfoxide or ethylene dichloride.

7. The preparation method according to claim 3, characterized in that: The reaction temperature is 60-120°C and the reaction time is 10-16h.

8. The preparation method according to claim 3, characterized in that: After the reaction is completed, a post-treatment step is also included; the post-treatment includes: extraction with ethyl acetate, washing with saturated sodium chloride water, removing the solvent by rotary evaporation, and separating and purifying the crude product by silica gel column chromatography.

9. Use of the multifunctional silanol compound according to any one of claims 1 to 2 in the preparation of a drug delivery system or a biomedical material.

10. Use of the multifunctional silanol compound according to any one of claims 1 to 2 in the organosilicon industry, coating industry or material science field.

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