WO2017159750A1 - Alkoxysilyl group-containing phosphorescent pigment and production method therefor - Google Patents

Alkoxysilyl group-containing phosphorescent pigment and production method therefor Download PDF

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WO2017159750A1
WO2017159750A1 PCT/JP2017/010497 JP2017010497W WO2017159750A1 WO 2017159750 A1 WO2017159750 A1 WO 2017159750A1 JP 2017010497 W JP2017010497 W JP 2017010497W WO 2017159750 A1 WO2017159750 A1 WO 2017159750A1
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group
bond
reaction
phosphorescent dye
substituted
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Japanese (ja)
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信一郎 礒部
洋平 松岡
駿太郎 又賀
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信一郎 礒部
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    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B57/00—Other synthetic dyes of known constitution
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B62/00—Reactive dyes, i.e. dyes which form covalent bonds with the substrates or which polymerise with themselves
    • C09B62/44—Reactive dyes, i.e. dyes which form covalent bonds with the substrates or which polymerise with themselves with the reactive group not directly attached to a heterocyclic ring
    • C09B62/78—Reactive dyes, i.e. dyes which form covalent bonds with the substrates or which polymerise with themselves with the reactive group not directly attached to a heterocyclic ring with other reactive groups
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence

Definitions

  • the present invention relates to an alkoxysilyl group-containing phosphorescent dye and a method for producing the same, and more particularly, an alkoxysilyl group-containing phosphorescent used for producing phosphorescent dye-containing silica particles used for detection of biomolecules such as nucleic acids, proteins, peptides, and saccharides.
  • the present invention relates to a dye and a method for producing the same.
  • Fluorescent nanoparticles are present in addition to organic fluorescent dyes.
  • Quantum Dots are well known as well-known fluorescent nanoparticles, with relatively high stability, strong fluorescence, multi-wavelength fluorescence with a single excitation light, and abundant color variations. Yes.
  • fluorescent dye-containing silica particles containing harmless organic fluorescent dyes
  • the fluorescent dye-containing silica particles are characterized by strong fluorescence because a large number of organic fluorescent dyes can be contained in silica.
  • silica particles containing phosphorescent dyes that can be expected to have higher quantum efficiency than fluorescent dyes have not been studied.
  • Silica particles containing organic phosphorescent dyes do not require an expensive filter that is necessary when using fluorescent dye-containing silica particles, and are not affected by background such as autofluorescence. There are advantages. Further, although the fluorescent dye-containing silica particles cannot be confirmed as fluorescence unless they are continuously excited, the phosphorescent dye-containing silica particles can be visually confirmed with phosphorescence once excited. However, organic phosphorescent dyes have very low luminous efficiency at room temperature, and few are known to emit light at room temperature in a solid state. Therefore, the phosphorescent pigment-containing silica particles have a problem that they do not emit light in a solid state at room temperature.
  • the present invention provides an alkoxysilyl group-containing phosphorescent dye and a method for producing the same, which can be used for the production of phosphorescent dye-containing silica particles capable of emitting light in a solid state at room temperature, by solving the above problems. Aimed at that.
  • the alkoxysilyl group-containing phosphorescent dye of the present invention is represented by the general formula X—Y—Q—Z—Si (R 1 ) n (OR 2 ) 3-n , where X is an organic phosphorescent dye.
  • Y is a direct bond, or — (CH 2 ) p — (p is an integer of 1 to 10) or — (O—CH 2 CH 2 ) q — (q is an integer of 1 to 10), and Q is an amide bond , Ether bond, thioether bond, thioester bond, thiourea bond, disulfide bond and polyoxyethylene bond, and Z is — (CH 2 ) m — or — (CH 2 ) 2 NH ( CH 2 ) 3 —, R 1 and R 2 are alkyl groups having 1 to 4 carbon atoms, n is 0 or 1, and m is an integer of 1 to 10.
  • the production method of the present invention is a production method of the above alkoxysilyl group-containing phosphorescent dye, wherein the organic phosphorescent dye comprises a succinimidyl ester group, an alcoholate group, an amino group, a mercapto group, a halogenated alkyl group, and It has one type of reactive group selected from the group consisting of terminal hydroxy group-containing polyoxyethylene groups, and includes a step of mixing the organic phosphorescent dye and a silane coupling agent.
  • the phosphor dye-containing silica particles of the present invention are characterized by containing a condensate of the above alkoxysilyl group-containing phosphor dye.
  • an expensive filter required when using fluorescent dye-containing silica particles is not required, and not only is not affected by the background such as autofluorescence, but also emits light in a solid state at room temperature. It has the excellent effect of being possible.
  • the alkoxysilyl group-containing phosphorescent dye of the present invention is represented by the general formula XYQZ-Si (R 1 ) n (OR 2 ) 3-n , where X is an organic phosphorescent dye and Y is a direct bond or- (CH 2 ) p — (p is an integer of 1 to 10) or — (O—CH 2 CH 2 ) q — (q is an integer of 1 to 10), Q is an amide bond, an ether bond, a thioether bond, At least one selected from a thioester bond, a thiourea bond, a disulfide bond, and a polyoxyethylene bond, and Z is — (CH 2 ) m — or — (CH 2 ) 2 NH (CH 2 ) 3 — , R 1 and R 2 are alkyl groups having 1 to 4 carbon atoms, n is 0 or 1, and m is
  • the organic phosphorescent dye (hereinafter also referred to as phosphorescent dye) used in the present invention is substituted or unsubstituted carbazole, substituted or unsubstituted dibenzofuran, substituted or unsubstituted thionaphthene, substituted or unsubstituted indole, substituted or unsubstituted. Mention may be made of at least one compound selected from the group consisting of 1,3,5-triazine. Preferably, it is carbazole and its substituted products.
  • substituted or unsubstituted carbazole can be represented by the following general formula.
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 are each independently a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkenyl group, Alkynyl group, alkyl ester group, phosphate ester group, sulfate ester group, nitrile group, hydroxyl group, cyano group, sulfonyl group, aldehyde group, pyridyl group, carboxylic acid group, amino group, quaternary ammonium salt, or substituent
  • the aromatic hydrocarbon group which may have is shown.
  • the substituent of the aromatic hydrocarbon group which may have a substituent includes a halogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an alkyl ester group, a phosphate ester group, a sulfate ester group, a nitrile.
  • N-substituted carbazole is preferable.
  • R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 other than N-substituted carbazole R 1 are a hydrogen atom, R 1 is an alkyl group having 1 to 4 carbon atoms, substituted Or it is an unsubstituted aromatic hydrocarbon.
  • the substituent of the substituted aromatic hydrocarbon include one or more halogen atoms, alkyl groups having 1 to 4 carbon atoms, or alkoxy groups having 1 to 4 carbon atoms.
  • N-methylphenyl carbazole N-ethyl carbazole, N-methoxyphenyl carbazole, N-phenyl carbazole, N-chlorophenyl carbazole, N-bromophenyl carbazole, N-iodophenyl carbazole, and the like.
  • the substituent includes a halogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an alkyl ester group, and a phosphate ester.
  • a halogen atom an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an alkyl ester group, and a phosphate ester.
  • the substituent of the aromatic hydrocarbon group which may have a substituent includes a halogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an alkyl ester group, a phosphate ester group, a sulfate ester group, a nitrile.
  • Y represents a direct bond or — (CH 2 ) p — (p is an integer of 1 to 10) or — (O—CH 2 CH 2 ) q — (q is an integer of 1 to 10).
  • p is preferably from 1 to 8, more preferably from 1 to 4.
  • Q is preferably 1 to 8, more preferably 1 to 4.
  • the Q is at least one bond selected from an amide bond, an ether bond, a thioether bond, a thioester bond, a thiourea bond, a disulfide bond, and a polyoxyethylene bond.
  • a polyoxyethylene bond Preferably, one of them, more preferably an amide bond or a polyoxyethylene bond.
  • the amide bond can be represented by —CO (NR) —, wherein R is hydrogen or an alkyl group having 1 to 4 carbon atoms, preferably R is hydrogen or a methyl group, more preferably a methyl group. This is because in the case of a methyl group (hereinafter referred to as N-methylamide bond), stronger phosphorescence can be obtained.
  • the polyoxyethylene bond can be represented by — (O—CH 2 CH 2 ) r —, where r is an integer of 1 to 10, preferably 1 to 5.
  • a plurality of bonds selected from amide bonds, ether bonds, thioether bonds, thioester bonds, thiourea bonds, disulfide bonds, and polyoxyethylene bonds can be used.
  • light can be emitted in a solid state at room temperature as in the case of using a single bond.
  • the above Q can be represented by-[Q1-Q2]-.
  • a bond selected from an amide bond, an ether bond, a thioether bond, a thioester bond, a thiourea bond, a disulfide bond, and a polyoxyethylene bond can be used independently.
  • an N-methylamide bond can be used for Q1 and an ether bond can be used for Q2.
  • the example is demonstrated using the following reaction formula.
  • Compound I is an active ester of phosphorescent dye X, which is reacted with N-methylhydroxylamine to obtain N-methylhydroxyl of Compound II, and Compound II is reacted with a halogenated alkylsilane.
  • compound IV in which an N-methylamide bond and an ether bond are linked can be obtained.
  • the Q may include a direct bond of three types of bonds-[Q1-Q2-Q3]-, or a linking group L between the bonds.
  • the linking group L examples include-[Q1-Q2-L-Q3]-.
  • Q1, Q2, and Q3 a bond selected from an amide bond, an ether bond, a thioether bond, a thioester bond, a thiourea bond, a disulfide bond, and a polyoxyethylene bond can be used independently.
  • L is — (CH 2 ) n — (n is an integer of 1 to 10).
  • an N-methylamide bond can be used for Q1
  • an ether bond can be used for Q2
  • a thioester bond, an amide bond, or an N-methylamide bond can be used for Q3.
  • the N-methylhydroxyl compound of compound II is reacted with a halogenated alkyl N-hydroxysuccinimide to obtain compound III which is an active ester in which an N-methylamide bond and an ether bond are linked.
  • n in the formula of the halogenated alkyl N-hydroxysuccinimide and n in the formula of the compound III are integers of 1 to 10.
  • compound III is reacted with mercaptosilane to obtain compound V.
  • Compound V has a thioester bond as Q3.
  • compound III is reacted with aminosilane to obtain compound VI.
  • Compound VI has an amide bond as Q3.
  • compound III is reacted with methylaminosilane to give compound VII.
  • Compound VII has an N-methylamide bond as Q3.
  • the example of the combination of a plurality of bonds described in the above reaction formula is an example, and combinations other than the above are also possible. Moreover, the combination of 4 or more types can also be used as needed.
  • n in the formula of mercaptosilane, aminosilane, and methylaminosilane is an integer of 1 to 10.
  • Z is — (CH 2 ) m — or — (CH 2 ) 2 NH (CH 2 ) 3 —, and m is an integer of 1 to 10. Preferred is — (CH 2 ) 3 —.
  • R 1 and R 2 of Si (R 1 ) n (OR 2 ) 3-n are alkyl groups having 1 to 4 carbon atoms, preferably a methyl group, an ethyl group, an n-propyl group, more preferably a methyl group. Group or ethyl group.
  • N is 0 or 1.
  • the alkoxysilyl group-containing phosphorescent dye of the present invention can be produced using the following method. That is, the organic phosphorescent dye has one reactive group selected from the group consisting of a succinimidyl ester group, an alcoholate group, an amino group, a mercapto group, and a terminal hydroxy group-containing polyoxyethylene group,
  • the method includes a step of mixing an organic phosphorescent dye and a silane coupling agent.
  • the phosphorescent dye used in the present invention has the reactive group described above, and reacts with the silane coupling agent to form a covalent bond and bind to the silane coupling agent.
  • the covalent bond is an amide bond, N-methylamide bond, ether bond, thioether bond, thioester bond, thiourea bond, disulfide bond or polyoxyethylene bond.
  • aminoalkylsilane can be used as the silane coupling agent
  • a succinimidyl ester group can be used as the reactive group of the phosphorescent dye.
  • a methyl-substituted aminoalkylsilane can be used as the silane coupling agent, and a succinimidyl ester group can be used as the reactive group of the phosphorescent dye.
  • a halogenated alkylsilane can be used as the silane coupling agent, and an alcoholate group can be used as the reactive group of the phosphorescent dye.
  • mercaptosilane can be used as the silane coupling agent, and a halogenated alkyl group can be used as the reactive group of the phosphorescent dye.
  • mercaptosilane When forming a thioester bond, mercaptosilane can be used as the silane coupling agent, and a succinimidyl ester group can be used as the reactive group of the phosphorescent dye.
  • isothiocyanate silane When forming a thiourea bond, isothiocyanate silane can be used as the silane coupling agent, and an amino group can be used as the reactive group of the phosphorescent dye.
  • mercaptosilane When a disulfide bond is formed, mercaptosilane can be used as the silane coupling agent, and a mercapto group can be used as the reactive group of the phosphorescent dye.
  • glycidyloxyalkylsilane When forming a polyoxyethylene bond, glycidyloxyalkylsilane can be used as the silane coupling agent, and a terminal hydroxy group-containing polyoxyethylene group can be used as the reactive group of
  • silane coupling agent aminoalkylsilane, glycidyloxyalkylsilane, mercaptosilane, isothiocyanate, isocyanate silane, halogenated silane and the like can be used.
  • Aminoalkylsilane is preferable.
  • aminoalkylsilanes include 3-aminopropyltriethoxysilane, 3- (2-aminoethylamino) propyltrimethoxysilane, 3- (2-aminoethylamino) propyldimethoxymethylsilane, 3- (2- Aminoethylamino) propyltriethoxysilane, 3-aminopropyldiethoxymethylsilane, 3-aminopropyltrimethoxysilane and the like can be mentioned, and 3-aminopropyltrimethoxysilane is preferred.
  • glycidyloxyalkylsilane examples include diethoxy (3-glycidyloxypropyl) methylsilane, 3-glycidyloxypropyltrimethoxysilane, 3-glycidyloxypropyl (dimethoxy) methylsilane, and triethoxy (3-glycidyloxypropyl) silane.
  • Examples of mercaptosilane include 3-mercaptopropylmethylmethoxysilane and 3-mercaptopropyltrimethoxysilane.
  • isocyanate silane examples include 3-isocyanatopropyltriethoxysilane and 3-isocyanatopropyltrimethoxysilane.
  • examples of the isothiocyanate include 3-thiocyanatopropyltriethoxysilane.
  • examples of the halogenated silane include (3-bromopropyl) trimethoxysilane, 3-trimethoxysilylpropyl chloride, 3-chloropropyldimethoxymethylsilane, 3-iodopropyltrimethoxysilane and the like.
  • the reaction between the phosphorescent dye and the silane coupling agent can be performed by mixing and stirring at a temperature of room temperature to 60 ° C. using dichloromethane, chloroform, DMF or the like as a solvent. If necessary, the solvent can be removed under reduced pressure and the reaction product can be taken out.
  • phosphorescent dye-containing silica particles can be produced using the alkoxysilyl group-containing phosphorescent dye of the present invention.
  • the method for producing phosphorescent pigment-containing silica particles is not particularly limited as long as it is a method for producing silica particles using a silane coupling agent.
  • a method in which an alkoxysilyl group-containing phosphorescent dye is mixed with an aqueous solution to form a dense fluorescent core, and the dense fluorescent core and a silica precursor are mixed to form a silica shell on the dense core can be used.
  • Synthesis example 1 The synthesis of a carbazole-substituted product containing 3-aminopropyltrimethoxysilane (hereinafter abbreviated as APS) as an alkoxysilyl group will be described. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
  • APS 3-aminopropyltrimethoxysilane
  • bromophenylcarbazole body 2 The synthesis procedure of bromophenylcarbazole body 2 is shown below.
  • Synthesis example 2 The synthesis of a carbazole substituted product containing 3-mercaptopropyltrimethoxysilane (hereinafter abbreviated as MPS) as an alkoxysilyl group will be described. In this synthesis example, a thioester bond was used for the bond to the alkoxysilyl group. A reaction example is shown below.
  • the yield was 0.04 g and the yield was 35%.
  • Synthesis example 3 The synthesis of a carbazole substituted product containing 3-mercaptopropyltrimethoxysilane (hereinafter abbreviated as MPS) as an alkoxysilyl group will be described. In this synthesis example, a thioether bond was used for the bond to the alkoxysilyl group. A reaction example is shown below.
  • Synthesis example 4 The synthesis of a carbazole substituted product containing 3-methylaminopropyltriethoxysilane (hereinafter abbreviated as MAPS) as an alkoxysilyl group will be described. In this synthesis example, an N-methylamide bond was used for the bond to the alkoxysilyl group. A reaction example is shown below.
  • MAPS 3-methylaminopropyltriethoxysilane
  • Synthesis example 5 Chlorophenylcarbazole was used as the carbazole substituent, and 3-aminopropyltrimethoxysilane was used as the alkoxysilyl group. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
  • Synthesis Example 6 The synthesis of a chlorocarbazole compound containing 3-methylaminopropyltriethoxysilane as an alkoxysilyl group will be described. In this synthesis example, an N-methylamide bond was used for the bond to the alkoxysilyl group. A reaction example is shown below.
  • Synthesis example 8 The synthesis of methylphenylcarbazole containing 3-methylaminopropyltriethoxysilane as an alkoxysilyl group will be described. In this synthesis example, an N-methylamide bond was used for the bond to the alkoxysilyl group. A reaction example is shown below.
  • Synthesis Example 9 The synthesis of a thionaphthene substituted product containing 3-aminopropyltriethoxysilane as an alkoxysilyl group will be described. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
  • Synthesis Example 10 The synthesis of an indole substitution product containing 3-aminopropyltriethoxysilane as an alkoxysilyl group will be described. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
  • Synthesis Example 11 The synthesis of a dibenzofuran substituted product containing 3-aminopropyltriethoxysilane as an alkoxysilyl group will be described. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
  • Bromophenylcarbazole-APS body 1 dissolved in chloroform was hung on a slide glass and dried to prepare a film sample.
  • the prepared sample was irradiated with ultraviolet rays, and the fading of the sample was observed with a digital camera or a fluorescence microscope every hour.
  • FIG. 1 shows images observed by a digital camera before UV irradiation and after 1 to 6 hours of UV irradiation. No fading was observed even after 6 hours of UV irradiation.
  • 2 and 3 show images observed with a fluorescence microscope. FIG. 2 and FIG. 3 differ in the observation location. Even when observed with a fluorescence microscope, no fading was observed after 6 hours of UV irradiation. A similar test was conducted on bromophenylcarbazole-APS bodies 2 and 3, but no photoregression was observed after 6 hours of ultraviolet irradiation.
  • FIG. 4 to 8 are images observed with a fluorescence microscope
  • FIG. 4 is a bromophenylcarbazole-MAPS form of Synthesis Example 4
  • FIG. 5 is a chlorophenylcarbazole form-APS form of Synthesis Example 5
  • FIG. 7 is an image of the methylphenylcarbazole-MAPS form of Synthesis Example 7
  • FIG. 8 is an image of the methylphenylcarbazole-MAPS form of Synthesis Example 8.
  • no fading was observed after 6 hours of ultraviolet irradiation. Similar effects were also observed in Synthesis Examples 9-11.
  • the alkoxysilyl group-containing phosphorescent dye of the present invention can emit phosphorescence at room temperature in a solid state.
  • organic phosphorescent dyes have a very low luminous efficiency at room temperature, and few are known to emit light at room temperature in a solid state.
  • Conventional phosphorescent dye-containing silica particles do not emit light at room temperature in a solid state.
  • the alkoxysilyl group-containing phosphorescent dye of the present invention emits phosphorescence at room temperature in a solid state, many uses can be expected as new nanoparticles containing the phosphorescent dye.

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Abstract

Provided are an alkoxysilyl group-containing phosphorescent pigment that can be used in production of phosphorescent pigment-containing silica particles that can emit light in a solid state at room temperature, and a method for producing the pigment. The alkoxysilyl group-containing phosphorescent pigment according to the present invention is represented by general formula X-Y-Q-Z-Si(R1)n(OR2)3-n, wherein X represents an organic phosphorescent pigment, Y represents a direct bond or -(CH2)p- (p represents an integer of 1-10) or -(O-CH2CH2)q- (q represents an integer of 1-10), Q represents at least one bond selected from an amide bond, an ether bond, a thioether bond, a thioester bond, a thiourea bond, a disulfide bond, and a polyoxyethylene bond, Z represents -(CH2)m- or -(CH2)2NH(CH2)3-, R1 and R2 represent an alkyl group having 1-4 carbon atoms, n represents 0 or 1, and m represents an integer of 1-10.

Description

アルコキシシリル基含有燐光色素およびその製造方法Alkoxysilyl group-containing phosphorescent dye and method for producing the same
　本発明は、アルコキシシリル基含有燐光色素およびその製造方法に関し、さらに詳しくは核酸、タンパク質、ペプチド類、そして糖類等の生体分子の検出に用いる燐光色素含有シリカ粒子の製造に用いるアルコキシシリル基含有燐光色素およびその製造方法に関する。 TECHNICAL FIELD The present invention relates to an alkoxysilyl group-containing phosphorescent dye and a method for producing the same, and more particularly, an alkoxysilyl group-containing phosphorescent used for producing phosphorescent dye-containing silica particles used for detection of biomolecules such as nucleic acids, proteins, peptides, and saccharides. The present invention relates to a dye and a method for producing the same.
　ニューバイオケミストリー分野では、現在特定遺伝子解析、遺伝子治療、テーラーメイド医療を目的とした研究が盛んに行われている。この分野では有機蛍光試薬を用いる研究が殆どであり蛍光色素が存在しなければ、ＤＮＡ解析や抗体を含むタンパク質を用いた解析技術は完成しなかったと言われている。これらの分野で主に使用されている既存の蛍光試薬として、シアニン骨格を有するＣｙ－ｄｙｅやローダミン骨格を有するＡｌｅｘａ　Ｆｌｕｏｒなどの有機蛍光色素が多く用いられている。 In the field of new biochemistry, research aimed at specific gene analysis, gene therapy, and tailor-made medicine is being actively conducted. In this field, most studies use organic fluorescent reagents, and it is said that analysis techniques using DNA analysis and proteins including antibodies have not been completed without the presence of fluorescent dyes. As an existing fluorescent reagent mainly used in these fields, organic fluorescent dyes such as Cy-dye having a cyanine skeleton and Alexa Fluor having a rhodamine skeleton are often used.
　また、有機蛍光色素の他に蛍光ナノ粒子が存在している。有名な蛍光ナノ粒子としてＱｕａｎｔｕｍ　Ｄｏｔｓなどが良く知られており、比較的安定性も高く、強い蛍光や単一の励起光による多波長蛍光、色調のバリエーションが豊富であるなどの特徴を有している。しかし、セレンやカドミウムなどの毒性元素を含んでいるため、安全性に問題を抱えている。これに代わる新たな技術として無害な有機蛍光色素を含むシリカ粒子（以下、蛍光色素含有シリカ粒子という）の開発が行われている（例えば、特許文献１）。この蛍光色素含有シリカ粒子は、シリカの中に有機蛍光色素を多数含有させる事が可能なため蛍光が強いなどの特徴がある。一方、蛍光色素に比べ高い量子効率の期待できる燐光色素を含むシリカ粒子については検討されていない。 Fluorescent nanoparticles are present in addition to organic fluorescent dyes. Quantum Dots are well known as well-known fluorescent nanoparticles, with relatively high stability, strong fluorescence, multi-wavelength fluorescence with a single excitation light, and abundant color variations. Yes. However, since it contains toxic elements such as selenium and cadmium, it has a safety problem. Development of silica particles containing harmless organic fluorescent dyes (hereinafter referred to as fluorescent dye-containing silica particles) has been performed as a new technology that replaces this (for example, Patent Document 1). The fluorescent dye-containing silica particles are characterized by strong fluorescence because a large number of organic fluorescent dyes can be contained in silica. On the other hand, silica particles containing phosphorescent dyes that can be expected to have higher quantum efficiency than fluorescent dyes have not been studied.
特開２００６－５１４７０８号公報JP 2006-514708 A
　有機燐光色素を含むシリカ粒子（以下、燐光色素含有シリカ粒子という）は、蛍光色素含有シリカ粒子を使用の際に必要となる高価なフィルターが不要となり、自家蛍光などのバックグラウンドの影響を受けない利点が存在する。また、蛍光色素含有シリカ粒子は励起させ続けなければ蛍光として確認ができないが、燐光色素含有シリカ粒子は、一旦励起させれば燐光を目視で確認することができる。しかしながら、有機燐光色素は、室温での発光効率が非常に低く、室温、固体状態で発光するものはほとんど知られていない。そのため、燐光色素含有シリカ粒子は、室温、固体状態で発光しないという問題がある。 Silica particles containing organic phosphorescent dyes (hereinafter referred to as phosphorescent dye-containing silica particles) do not require an expensive filter that is necessary when using fluorescent dye-containing silica particles, and are not affected by background such as autofluorescence. There are advantages. Further, although the fluorescent dye-containing silica particles cannot be confirmed as fluorescence unless they are continuously excited, the phosphorescent dye-containing silica particles can be visually confirmed with phosphorescence once excited. However, organic phosphorescent dyes have very low luminous efficiency at room temperature, and few are known to emit light at room temperature in a solid state. Therefore, the phosphorescent pigment-containing silica particles have a problem that they do not emit light in a solid state at room temperature.
　そこで、本発明は、上記の課題を解決し、室温、固体状態で発光することの可能な燐光色素含有シリカ粒子の製造に用いることができる、アルコキシシリル基含有燐光色素およびその製造方法を提供することを目的とした。 Accordingly, the present invention provides an alkoxysilyl group-containing phosphorescent dye and a method for producing the same, which can be used for the production of phosphorescent dye-containing silica particles capable of emitting light in a solid state at room temperature, by solving the above problems. Aimed at that.
　上記課題を解決するため、本発明のアルコキシシリル基含有燐光色素は、一般式Ｘ―Ｙ－Ｑ－Ｚ－Ｓｉ（Ｒ１）ｎ（ＯＲ２）３－ｎで表され、Ｘが有機燐光色素、Ｙが直接結合あるいは－（ＣＨ２）ｐ－（ｐは１から１０の整数）または－（Ｏ－ＣＨ２ＣＨ２）ｑ－（ｑは１から１０の整数）であり、Ｑはアミド結合、エーテル結合、チオエーテル結合、チオエステル結合、チオウレア結合、ジスルフィド結合およびポリオキシエチレン結合から選択される少なくとも１種の結合であり、Ｚは－（ＣＨ２）ｍ－または－（ＣＨ２）２ＮＨ（ＣＨ２）３－であり、Ｒ１とＲ２は炭素数１から４のアルキル基であり、ｎは０または１であり、ｍは１から１０の整数であることを特徴とする。 In order to solve the above problems, the alkoxysilyl group-containing phosphorescent dye of the present invention is represented by the general formula X—Y—Q—Z—Si (R 1 ) n (OR 2 ) 3-n , where X is an organic phosphorescent dye. , Y is a direct bond, or — (CH 2 ) p — (p is an integer of 1 to 10) or — (O—CH 2 CH 2 ) q — (q is an integer of 1 to 10), and Q is an amide bond , Ether bond, thioether bond, thioester bond, thiourea bond, disulfide bond and polyoxyethylene bond, and Z is — (CH 2 ) m — or — (CH 2 ) 2 NH ( CH 2 ) 3 —, R 1 and R 2 are alkyl groups having 1 to 4 carbon atoms, n is 0 or 1, and m is an integer of 1 to 10.
　また、本発明の製造方法は、上記のアルコキシシリル基含有燐光色素の製造方法であって、前記有機燐光色素が、スクシンイミジルエステル基、アルコラート基、アミノ基、メルカプト基、ハロゲン化アルキル基および末端ヒドロキシ基含有ポリオキシエチレン基からなる群から選択される１種の反応性基を有し、前記有機燐光色素とシランカップリング剤を混合する工程を含むことを特徴とする。 The production method of the present invention is a production method of the above alkoxysilyl group-containing phosphorescent dye, wherein the organic phosphorescent dye comprises a succinimidyl ester group, an alcoholate group, an amino group, a mercapto group, a halogenated alkyl group, and It has one type of reactive group selected from the group consisting of terminal hydroxy group-containing polyoxyethylene groups, and includes a step of mixing the organic phosphorescent dye and a silane coupling agent.
　また、本発明の燐光色素含有シリカ粒子は、上記のアルコキシシリル基含有燐光色素の縮合体を含むことを特徴とする。 The phosphor dye-containing silica particles of the present invention are characterized by containing a condensate of the above alkoxysilyl group-containing phosphor dye.
　本発明によれば、蛍光色素含有シリカ粒子を使用の際に必要となる高価なフィルターが不要となり、自家蛍光などのバックグラウンドの影響を受けないだけでなく、室温、固体状態で発光することが可能なという優れた効果を有する。 According to the present invention, an expensive filter required when using fluorescent dye-containing silica particles is not required, and not only is not affected by the background such as autofluorescence, but also emits light in a solid state at room temperature. It has the excellent effect of being possible.
本発明のアルコキシシリル基含有燐光色素の紫外線退光試験の結果を示す画像である。It is an image which shows the result of the ultraviolet-ray fading test of the alkoxy silyl group containing phosphorescent dye of this invention. 本発明のアルコキシシリル基含有燐光色素の別の紫外線退光試験の結果を示す画像である。It is an image which shows the result of another ultraviolet-ray fading test of the alkoxy silyl group containing phosphorescent dye of this invention. 本発明のアルコキシシリル基含有燐光色素の別の紫外線退光試験の結果を示す画像である。It is an image which shows the result of another ultraviolet-ray fading test of the alkoxy silyl group containing phosphorescent dye of this invention. 本発明のアルコキシシリル基含有燐光色素の別の紫外線退光試験の結果を示す画像である。It is an image which shows the result of another ultraviolet-ray fading test of the alkoxy silyl group containing phosphorescent dye of this invention. 本発明のアルコキシシリル基含有燐光色素の別の紫外線退光試験の結果を示す画像である。It is an image which shows the result of another ultraviolet-ray fading test of the alkoxy silyl group containing phosphorescent dye of this invention. 本発明のアルコキシシリル基含有燐光色素の別の紫外線退光試験の結果を示す画像である。It is an image which shows the result of another ultraviolet-ray fading test of the alkoxy silyl group containing phosphorescent dye of this invention. 本発明のアルコキシシリル基含有燐光色素の別の紫外線退光試験の結果を示す画像である。It is an image which shows the result of another ultraviolet-ray fading test of the alkoxy silyl group containing phosphorescent dye of this invention. 本発明のアルコキシシリル基含有燐光色素の別の紫外線退光試験の結果を示す画像である。It is an image which shows the result of another ultraviolet-ray fading test of the alkoxy silyl group containing phosphorescent dye of this invention.
　以下、本発明の実施の形態について詳細に説明する。
　本発明のアルコキシシリル基含有燐光色素は、一般式Ｘ―Ｙ－Ｑ－Ｚ－Ｓｉ（Ｒ１）ｎ（ＯＲ２）３－ｎで表され、Ｘが有機燐光色素、Ｙが直接結合あるいは－（ＣＨ２）ｐ－（ｐは１から１０の整数）または－（Ｏ－ＣＨ２ＣＨ２）ｑ－（ｑは１から１０の整数）であり、Ｑはアミド結合、エーテル結合、チオエーテル結合、チオエステル結合、チオウレア結合、ジスルフィド結合およびポリオキシエチレン結合から選択される少なくとも１種の結合であり、Ｚは－（ＣＨ２）ｍ－または－（ＣＨ２）２ＮＨ（ＣＨ２）３－であり、Ｒ１とＲ２は炭素数１から４のアルキル基であり、ｎは０または１であり、ｍは１から１０の整数であることを特徴とするものである。 Hereinafter, embodiments of the present invention will be described in detail.
The alkoxysilyl group-containing phosphorescent dye of the present invention is represented by the general formula XYQZ-Si (R 1 ) n (OR 2 ) 3-n , where X is an organic phosphorescent dye and Y is a direct bond or- (CH 2 ) p — (p is an integer of 1 to 10) or — (O—CH 2 CH 2 ) q — (q is an integer of 1 to 10), Q is an amide bond, an ether bond, a thioether bond, At least one selected from a thioester bond, a thiourea bond, a disulfide bond, and a polyoxyethylene bond, and Z is — (CH 2 ) m — or — (CH 2 ) 2 NH (CH 2 ) 3 — , R 1 and R 2 are alkyl groups having 1 to 4 carbon atoms, n is 0 or 1, and m is an integer of 1 to 10.
　本発明に用いる有機燐光色素（以下、燐光色素ともいう）は、置換または無置換のカルバゾール、置換または無置換のジベンゾフラン、置換または無置換のチオナフテン、置換または無置換のインドール、置換または無置換の１，３，５－トリアジンから成る群から選択される少なくとも１種の化合物を挙げることができる。好ましくは、カルバゾールおよびその置換体である。 The organic phosphorescent dye (hereinafter also referred to as phosphorescent dye) used in the present invention is substituted or unsubstituted carbazole, substituted or unsubstituted dibenzofuran, substituted or unsubstituted thionaphthene, substituted or unsubstituted indole, substituted or unsubstituted. Mention may be made of at least one compound selected from the group consisting of 1,3,5-triazine. Preferably, it is carbazole and its substituted products.
　例えば、置換または無置換のカルバゾールは、以下の一般式で表すことができる。 For example, substituted or unsubstituted carbazole can be represented by the following general formula.
Figure JPOXMLDOC01-appb-C000001
Figure JPOXMLDOC01-appb-C000001
　ここで、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５、Ｒ６、Ｒ７、Ｒ８、Ｒ９は、それぞれ独立に、水素原子、ハロゲン原子、アルキル基、アルコキシ基、アルケニル基、アルキニル基、アルキルエステル基、リン酸エステル基、硫酸エステル基、ニトリル基、ヒドロキシル基、シアノ基、スルホニル基、アルデヒド基、ピリジル基、カルボン酸基、アミノ基、四級アンモニウム塩、または置換基を有してもよい芳香族炭化水素基を示す。ここで、四級アンモニウム塩の対イオンとしては、Ｃｌ－、Ｂｒ－、Ｉ－、ＣＨ３ＳＯ３ －、ＣＦ３ＳＯ３ －等を挙げることができる。また、置換基を有してもよい芳香族炭化水素基の置換基としては、ハロゲン原子、アルキル基、アルコキシ基、アルケニル基、アルキニル基、アルキルエステル基、リン酸エステル基、硫酸エステル基、ニトリル基、ヒドロキシル基、シアノ基、スルホニル基、アルデヒド基、ピリジル基、カルボン酸基、アミノ基または四級アンモニウム塩を挙げることができる。 Here, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 are each independently a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkenyl group, Alkynyl group, alkyl ester group, phosphate ester group, sulfate ester group, nitrile group, hydroxyl group, cyano group, sulfonyl group, aldehyde group, pyridyl group, carboxylic acid group, amino group, quaternary ammonium salt, or substituent The aromatic hydrocarbon group which may have is shown. Here, as a counter ion of the quaternary ammonium salt, Cl − , Br − , I − , CH 3 SO 3 − , CF 3 SO 3 — and the like can be mentioned. In addition, the substituent of the aromatic hydrocarbon group which may have a substituent includes a halogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an alkyl ester group, a phosphate ester group, a sulfate ester group, a nitrile. Groups, hydroxyl groups, cyano groups, sulfonyl groups, aldehyde groups, pyridyl groups, carboxylic acid groups, amino groups or quaternary ammonium salts.
　置換カルバゾールとしては、Ｎ－置換カルバゾールが好ましい。Ｎ－置換カルバゾールＲ１以外のＲ２、Ｒ３、Ｒ４、Ｒ５、Ｒ６、Ｒ７、Ｒ８、Ｒ９が水素原子であり、Ｒ１が炭素数１から４のアルキル基、置換または無置換の芳香族炭化水素である。置換芳香族炭化水素の置換基としては、単数または複数の、ハロゲン原子、炭素数１から４のアルキル基、または炭素数１から４のアルコキシ基を挙げることができる。具体例としては、Ｎ－メチルフェニルカルバゾール、Ｎ－エチルカルバゾール、Ｎ－メトキシフェニルカルバゾール、Ｎ－フェニルカルバゾール、Ｎ－クロロフェニルカルバゾール、Ｎ－ブロモフェニルカルバゾール、Ｎ－ヨードフェニルカルバゾール等を挙げることができる。 As the substituted carbazole, N-substituted carbazole is preferable. R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 other than N-substituted carbazole R 1 are a hydrogen atom, R 1 is an alkyl group having 1 to 4 carbon atoms, substituted Or it is an unsubstituted aromatic hydrocarbon. Examples of the substituent of the substituted aromatic hydrocarbon include one or more halogen atoms, alkyl groups having 1 to 4 carbon atoms, or alkoxy groups having 1 to 4 carbon atoms. Specific examples include N-methylphenyl carbazole, N-ethyl carbazole, N-methoxyphenyl carbazole, N-phenyl carbazole, N-chlorophenyl carbazole, N-bromophenyl carbazole, N-iodophenyl carbazole, and the like.
　また、置換ジベンゾフラン、置換チオナフテン、置換インドール、および置換１，３，５－トリアジンの場合の置換基としては、ハロゲン原子、アルキル基、アルコキシ基、アルケニル基、アルキニル基、アルキルエステル基、リン酸エステル基、硫酸エステル基、ニトリル基、ヒドロキシル基、シアノ基、スルホニル基、アルデヒド基、ピリジル基、カルボン酸基、アミノ基、四級アンモニウム塩、または置換基を有してもよい芳香族炭化水素基を示す。ここで、四級アンモニウム塩の対イオンとしては、Ｃｌ－、Ｂｒ－、Ｉ－、ＣＨ３ＳＯ３ －、ＣＦ３ＳＯ３ －等を挙げることができる。また、置換基を有してもよい芳香族炭化水素基の置換基としては、ハロゲン原子、アルキル基、アルコキシ基、アルケニル基、アルキニル基、アルキルエステル基、リン酸エステル基、硫酸エステル基、ニトリル基、ヒドロキシル基、シアノ基、スルホニル基、アルデヒド基、ピリジル基、カルボン酸基、アミノ基または四級アンモニウム塩を挙げることができる。 In the case of substituted dibenzofuran, substituted thionaphthene, substituted indole, and substituted 1,3,5-triazine, the substituent includes a halogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an alkyl ester group, and a phosphate ester. Group, sulfate group, nitrile group, hydroxyl group, cyano group, sulfonyl group, aldehyde group, pyridyl group, carboxylic acid group, amino group, quaternary ammonium salt, or aromatic hydrocarbon group which may have a substituent Indicates. Here, as a counter ion of the quaternary ammonium salt, Cl − , Br − , I − , CH 3 SO 3 − , CF 3 SO 3 — and the like can be mentioned. In addition, the substituent of the aromatic hydrocarbon group which may have a substituent includes a halogen atom, an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, an alkyl ester group, a phosphate ester group, a sulfate ester group, a nitrile. Groups, hydroxyl groups, cyano groups, sulfonyl groups, aldehyde groups, pyridyl groups, carboxylic acid groups, amino groups or quaternary ammonium salts.
　前記のＹは、直接結合あるいは－（ＣＨ２）ｐ－（ｐは１から１０の整数）または－（Ｏ－ＣＨ２ＣＨ２）ｑ－（ｑは１から１０の整数）を示す。ｐは好ましくは１から８、より好ましくは１から４である。また、ｑは好ましくは１から８、より好ましくは１から４である。 Y represents a direct bond or — (CH 2 ) p — (p is an integer of 1 to 10) or — (O—CH 2 CH 2 ) q — (q is an integer of 1 to 10). p is preferably from 1 to 8, more preferably from 1 to 4. Q is preferably 1 to 8, more preferably 1 to 4.
　また、前記のＱは、アミド結合、エーテル結合、チオエーテル結合、チオエステル結合、チオウレア結合、ジスルフィド結合およびポリオキシエチレン結合から選択される少なくとも１種の結合である。好ましくは、それらの中の１種の結合、より好ましくは、アミド結合またはポリオキシエチレン結合である。なお、アミド結合は、－ＣＯ（ＮＲ）－で表すことができ、Ｒは水素または炭素数１から４のアルキル基であり、好ましくはＲは水素またはメチル基、より好ましくはメチル基である。メチル基の場合（以下、Ｎ－メチルアミド結合という）、より強い燐光を得ることができるからである。また、ポリオキシエチレン結合は、－（Ｏ－ＣＨ２ＣＨ２）ｒ－で表すことができ、ｒは１から１０の整数、好ましくは１から５の整数である。 The Q is at least one bond selected from an amide bond, an ether bond, a thioether bond, a thioester bond, a thiourea bond, a disulfide bond, and a polyoxyethylene bond. Preferably, one of them, more preferably an amide bond or a polyoxyethylene bond. The amide bond can be represented by —CO (NR) —, wherein R is hydrogen or an alkyl group having 1 to 4 carbon atoms, preferably R is hydrogen or a methyl group, more preferably a methyl group. This is because in the case of a methyl group (hereinafter referred to as N-methylamide bond), stronger phosphorescence can be obtained. The polyoxyethylene bond can be represented by — (O—CH 2 CH 2 ) r —, where r is an integer of 1 to 10, preferably 1 to 5.
　前記のＱとして、アミド結合、エーテル結合、チオエーテル結合、チオエステル結合、チオウレア結合、ジスルフィド結合およびポリオキシエチレン結合から選択される複数の結合を用いることもできる。この場合も単数の結合を用いた場合と同様に、室温、固体状態で発光することができる。例えば、２種の結合を用いる場合、前記のＱは、－[Ｑ１－Ｑ２]－で表すことができる。ここで、Ｑ１とＱ２には、それぞれ独立に、アミド結合、エーテル結合、チオエーテル結合、チオエステル結合、チオウレア結合、ジスルフィド結合およびポリオキシエチレン結合から選択される結合を用いることができる。例えば、Ｑ１にＮ－メチルアミド結合、Ｑ２にエーテル結合を用いることができる。その例について以下の反応式を用いて説明する。 As the Q, a plurality of bonds selected from amide bonds, ether bonds, thioether bonds, thioester bonds, thiourea bonds, disulfide bonds, and polyoxyethylene bonds can be used. In this case, light can be emitted in a solid state at room temperature as in the case of using a single bond. For example, when two types of bonds are used, the above Q can be represented by-[Q1-Q2]-. Here, for Q1 and Q2, a bond selected from an amide bond, an ether bond, a thioether bond, a thioester bond, a thiourea bond, a disulfide bond, and a polyoxyethylene bond can be used independently. For example, an N-methylamide bond can be used for Q1 and an ether bond can be used for Q2. The example is demonstrated using the following reaction formula.
Figure JPOXMLDOC01-appb-C000002
Figure JPOXMLDOC01-appb-C000002
　上記の反応式中、化合物Ｉは、燐光色素Ｘの活性エステル体であり、Ｎ－メチルヒドロキシルアミンと反応させて化合物ＩＩのＮ－メチルヒドロキシル体を得、化合物ＩＩをハロゲン化アルキルシランと反応させて、Ｎ－メチルアミド結合とエーテル結合が連結した化合物ＩＶを得ることができる。 In the above reaction formula, Compound I is an active ester of phosphorescent dye X, which is reacted with N-methylhydroxylamine to obtain N-methylhydroxyl of Compound II, and Compound II is reacted with a halogenated alkylsilane. Thus, compound IV in which an N-methylamide bond and an ether bond are linked can be obtained.
　前記のＱとして、３種の結合を用いる場合、前記のＱは、３種の結合の直接結合－[Ｑ１－Ｑ２－Ｑ３]－、または各結合の間に連結基Ｌを含んでもよい。連結基Ｌを含む場合として、例えば、－[Ｑ１－Ｑ２－Ｌ－Ｑ３]－を挙げることができる。ここで、Ｑ１，Ｑ２，Ｑ３には、それぞれ独立に、アミド結合、エーテル結合、チオエーテル結合、チオエステル結合、チオウレア結合、ジスルフィド結合およびポリオキシエチレン結合から選択される結合を用いることができる。また、Ｌは、－（ＣＨ２）ｎ－（ｎは１から１０の整数）である。例えば、Ｑ１にＮ－メチルアミド結合を用い、Ｑ２にエーテル結合を用い、Ｑ３にチオエステル結合、アミド結合、またはＮ－メチルアミド結合を用いることができる。それらの例について以下の反応式を用いて説明する。 When three types of bonds are used as the Q, the Q may include a direct bond of three types of bonds-[Q1-Q2-Q3]-, or a linking group L between the bonds. Examples of the case where the linking group L is included include-[Q1-Q2-L-Q3]-. Here, as Q1, Q2, and Q3, a bond selected from an amide bond, an ether bond, a thioether bond, a thioester bond, a thiourea bond, a disulfide bond, and a polyoxyethylene bond can be used independently. L is — (CH 2 ) n — (n is an integer of 1 to 10). For example, an N-methylamide bond can be used for Q1, an ether bond can be used for Q2, and a thioester bond, an amide bond, or an N-methylamide bond can be used for Q3. These examples will be described using the following reaction formula.
Figure JPOXMLDOC01-appb-C000003
Figure JPOXMLDOC01-appb-C000003
　上記の反応式では、化合物ＩＩのＮ－メチルヒドロキシル体をハロゲン化アルキルＮ－ヒドロキシコハク酸イミドと反応させて、Ｎ－メチルアミド結合とエーテル結合が連結した活性エステル体である化合物ＩＩＩを得る。なお、上記の反応式中のハロゲン化アルキルＮ－ヒドロキシコハク酸イミドの式中のｎと化合物ＩＩＩの式中のｎは１から１０の整数である。次に、以下に示す反応を行う。 In the above reaction formula, the N-methylhydroxyl compound of compound II is reacted with a halogenated alkyl N-hydroxysuccinimide to obtain compound III which is an active ester in which an N-methylamide bond and an ether bond are linked. In the above reaction formula, n in the formula of the halogenated alkyl N-hydroxysuccinimide and n in the formula of the compound III are integers of 1 to 10. Next, the following reaction is performed.
Figure JPOXMLDOC01-appb-C000004
Figure JPOXMLDOC01-appb-C000004
　上記の反応式中、化合物ＩＩＩをメルカプトシランと反応させて、化合物Ｖを得る。化合物Ｖは、Ｑ３としてチオエステル結合を有している。また、上記の反応式中、化合物ＩＩＩをアミノシランと反応させて、化合物ＶＩを得る。化合物ＶＩは、Ｑ３としてアミド結合を有している。また、上記の反応式中、化合物ＩＩＩをメチルアミノシランと反応させて、化合物ＶＩＩを得る。化合物ＶＩＩは、Ｑ３としてＮ－メチルアミド結合を有している。
なお、上記の反応式で説明した複数の結合の組み合わせの例は、一例であって、上記以外の組み合わせも可能である。また、必要に応じて４種以上の組み合わせも用いることができる。なお、上記の反応式中、メルカプトシラン、アミノシラン、メチルアミノシランの式中のｎは１から１０の整数である。 In the above reaction formula, compound III is reacted with mercaptosilane to obtain compound V. Compound V has a thioester bond as Q3. Further, in the above reaction formula, compound III is reacted with aminosilane to obtain compound VI. Compound VI has an amide bond as Q3. In the above reaction formula, compound III is reacted with methylaminosilane to give compound VII. Compound VII has an N-methylamide bond as Q3.
The example of the combination of a plurality of bonds described in the above reaction formula is an example, and combinations other than the above are also possible. Moreover, the combination of 4 or more types can also be used as needed. In the above reaction formula, n in the formula of mercaptosilane, aminosilane, and methylaminosilane is an integer of 1 to 10.
　また、前記のＺは－（ＣＨ２）ｍ－または－（ＣＨ２）２ＮＨ（ＣＨ２）３－であり、ｍは１から１０の整数である。好ましくは－（ＣＨ２）３－である。 Z is — (CH 2 ) m — or — (CH 2 ) 2 NH (CH 2 ) 3 —, and m is an integer of 1 to 10. Preferred is — (CH 2 ) 3 —.
　また、Ｓｉ（Ｒ１）ｎ（ＯＲ２）３－ｎのＲ１とＲ２は炭素数１から４のアルキル基であり、好ましくはメチル基、エチル基、ｎ－プロピル基、より好ましくはメチル基またはエチル基である。また、ｎは０または１である。 In addition, R 1 and R 2 of Si (R 1 ) n (OR 2 ) 3-n are alkyl groups having 1 to 4 carbon atoms, preferably a methyl group, an ethyl group, an n-propyl group, more preferably a methyl group. Group or ethyl group. N is 0 or 1.
　また、本発明のアルコキシシリル基含有燐光色素は、以下の方法を用いて製造できる。すなわち、前記有機燐光色素が、スクシンイミジルエステル基、アルコラート基、アミノ基、メルカプト基、および末端ヒドロキシ基含有ポリオキシエチレン基からなる群から選択される１種の反応性基を有し、前記有機燐光色素とシランカップリング剤を混合する工程を含むことを特徴とするものである。 Further, the alkoxysilyl group-containing phosphorescent dye of the present invention can be produced using the following method. That is, the organic phosphorescent dye has one reactive group selected from the group consisting of a succinimidyl ester group, an alcoholate group, an amino group, a mercapto group, and a terminal hydroxy group-containing polyoxyethylene group, The method includes a step of mixing an organic phosphorescent dye and a silane coupling agent.
　本発明に用いる燐光色素は、上記の反応性基を有しており、シランカップリング剤と反応することで共有結合を形成してシランカップリング剤と結合する。共有結合として、アミド結合、Ｎ－メチルアミド結合、エーテル結合、チオエーテル結合、チオエステル結合、チオウレア結合、ジスルフィド結合またはポリオキシエチレン結合である。アミド結合を形成する場合、シランカップリング剤にはアミノアルキルシランを用い、燐光色素の反応性基としては、スクシンイミジルエステル基を用いることができる。また、Ｎ－メチルアミド結合を形成する場合、シランカップリング剤にはメチル置換アミノアルキルシランを用い、燐光色素の反応性基としては、スクシンイミジルエステル基を用いることができる。また、エーテル結合を形成する場合、シランカップリング剤にはハロゲン化アルキルシランを用い、燐光色素の反応性基としては、アルコラート基を用いることができる。また、チオエーテル結合を形成する場合、シランカップリング剤にはメルカプトシランを用い、燐光色素の反応性基としては、ハロゲン化アルキル基を用いることができる。また、チオエステル結合を形成する場合、シランカップリング剤にはメルカプトシランを用い、燐光色素の反応性基としては、スクシンイミジルエステル基を用いることができる。また、チオウレア結合を形成する場合、シランカップリング剤にはイソチオシアネートシランを用い、燐光色素の反応性基としては、アミノ基を用いることができる。また、ジスルフィド結合を形成する場合、シランカップリング剤にはメルカプトシランを用い、燐光色素の反応性基としては、メルカプト基を用いることができる。また、ポリオキシエチレン結合を形成する場合、シランカップリング剤にはグリシジルオキシアルキルシランを用い、燐光色素の反応性基としては、末端ヒドロキシ基含有ポリオキシエチレン基を用いることができる。 The phosphorescent dye used in the present invention has the reactive group described above, and reacts with the silane coupling agent to form a covalent bond and bind to the silane coupling agent. The covalent bond is an amide bond, N-methylamide bond, ether bond, thioether bond, thioester bond, thiourea bond, disulfide bond or polyoxyethylene bond. When an amide bond is formed, aminoalkylsilane can be used as the silane coupling agent, and a succinimidyl ester group can be used as the reactive group of the phosphorescent dye. When an N-methylamide bond is formed, a methyl-substituted aminoalkylsilane can be used as the silane coupling agent, and a succinimidyl ester group can be used as the reactive group of the phosphorescent dye. When an ether bond is formed, a halogenated alkylsilane can be used as the silane coupling agent, and an alcoholate group can be used as the reactive group of the phosphorescent dye. When forming a thioether bond, mercaptosilane can be used as the silane coupling agent, and a halogenated alkyl group can be used as the reactive group of the phosphorescent dye. When forming a thioester bond, mercaptosilane can be used as the silane coupling agent, and a succinimidyl ester group can be used as the reactive group of the phosphorescent dye. When forming a thiourea bond, isothiocyanate silane can be used as the silane coupling agent, and an amino group can be used as the reactive group of the phosphorescent dye. When a disulfide bond is formed, mercaptosilane can be used as the silane coupling agent, and a mercapto group can be used as the reactive group of the phosphorescent dye. When forming a polyoxyethylene bond, glycidyloxyalkylsilane can be used as the silane coupling agent, and a terminal hydroxy group-containing polyoxyethylene group can be used as the reactive group of the phosphorescent dye.
　シランカップリング剤には、アミノアルキルシラン、グリシジルオキシアルキルシラン、メルカプトシラン、イソチオシアネート、イソシアネートシラン、ハロゲン化シラン等を用いることができる。好ましくは、アミノアルキルシランである。アミノアルキルシランの具体例としては、３－アミノプロピルトリエトキシシラン、３－（２－アミノエチルアミノ）プロピルトリメトキシシラン、３－（２－アミノエチルアミノ）プロピルジメトキシメチルシラン、３－（２－アミノエチルアミノ）プロピルトリエトキシシラン、３－アミノプロピルジエトキシメチルシラン、３－アミノプロピルトリメトキシシラン等を挙げることができるが、好ましくは３－アミノプロピルトリメトキシシランである。また、グリシジルオキシアルキルシランの具体例としては、ジエトキシ（３－グリシジルオキシプロピル）メチルシラン、３－グリシジルオキシプロピルトリメトキシシラン、３－グリシジルオキシプロピル（ジメトキシ）メチルシラン、トリエトキシ（３－グリシジルオキシプロピル）シラン等を挙げることができる。また、メルカプトシランには、３－メルカプトプロピルメチルメトキシシランや３－メルカプトプロピルトリメトキシシランを挙げることができる。また、イソシアネートシランには、３－イソシアネートプロピルトリエトキシシランや３－イソシアネートプロピルトリメトキシシランを挙げることができる。また、イソチオシアネートには、３－チオシアナトプロピルトリエトキシシランを挙げることができる。また、ハロゲン化シランには、（３－ブロモプロピル）トリメトキシシラン、３－トリメトキシシリルプロピルクロライド、３－クロロプロピルジメトキシメチルシラン、３－ヨードプロピルトリメトキシシラン等を挙げることができる。 As the silane coupling agent, aminoalkylsilane, glycidyloxyalkylsilane, mercaptosilane, isothiocyanate, isocyanate silane, halogenated silane and the like can be used. Aminoalkylsilane is preferable. Specific examples of aminoalkylsilanes include 3-aminopropyltriethoxysilane, 3- (2-aminoethylamino) propyltrimethoxysilane, 3- (2-aminoethylamino) propyldimethoxymethylsilane, 3- (2- Aminoethylamino) propyltriethoxysilane, 3-aminopropyldiethoxymethylsilane, 3-aminopropyltrimethoxysilane and the like can be mentioned, and 3-aminopropyltrimethoxysilane is preferred. Specific examples of glycidyloxyalkylsilane include diethoxy (3-glycidyloxypropyl) methylsilane, 3-glycidyloxypropyltrimethoxysilane, 3-glycidyloxypropyl (dimethoxy) methylsilane, and triethoxy (3-glycidyloxypropyl) silane. Etc. Examples of mercaptosilane include 3-mercaptopropylmethylmethoxysilane and 3-mercaptopropyltrimethoxysilane. Examples of the isocyanate silane include 3-isocyanatopropyltriethoxysilane and 3-isocyanatopropyltrimethoxysilane. In addition, examples of the isothiocyanate include 3-thiocyanatopropyltriethoxysilane. Examples of the halogenated silane include (3-bromopropyl) trimethoxysilane, 3-trimethoxysilylpropyl chloride, 3-chloropropyldimethoxymethylsilane, 3-iodopropyltrimethoxysilane and the like.
　燐光色素とシランカップリング剤との反応は、溶媒にジクロロメタン、クロロホルム、ＤＭＦ等を用い、室温から６０℃の温度で、混合攪拌することにより行うことができる。必要に応じて溶媒を減圧等により除去して反応物を取り出すことができる。 The reaction between the phosphorescent dye and the silane coupling agent can be performed by mixing and stirring at a temperature of room temperature to 60 ° C. using dichloromethane, chloroform, DMF or the like as a solvent. If necessary, the solvent can be removed under reduced pressure and the reaction product can be taken out.
　また、本発明のアルコキシシリル基含有燐光色素を用いて燐光色素含有シリカ粒子を製造することができる。燐光色素含有シリカ粒子を製造する方法は、シランカップリング剤を用いてシリカ粒子を製造する方法であれば特に限定されない。例えば、アルコキシシリル基含有燐光色素を水溶液と混合して密集蛍光コアを形成し、その密集蛍光コアとシリカ前駆体を混合して密集コア上にシリカ殻を形成する方法を用いることができる。 In addition, phosphorescent dye-containing silica particles can be produced using the alkoxysilyl group-containing phosphorescent dye of the present invention. The method for producing phosphorescent pigment-containing silica particles is not particularly limited as long as it is a method for producing silica particles using a silane coupling agent. For example, a method in which an alkoxysilyl group-containing phosphorescent dye is mixed with an aqueous solution to form a dense fluorescent core, and the dense fluorescent core and a silica precursor are mixed to form a silica shell on the dense core can be used.
　以下、実施例を用いて本発明をさらに詳細に説明するが、本発明の範囲は以下の実施例により限定されるものではない。 Hereinafter, the present invention will be described in more detail using examples, but the scope of the present invention is not limited by the following examples.
合成例１
　アルコキシシリル基として３－アミノプロピルトリメトキシシラン（以下、ＡＰＳと略す）を含むカルバゾール置換体の合成について説明する。本合成例では、アルコキシシリル基との結合にアミド結合を用いた。
（１）ブロモフェニルカルバゾール体２の合成
　ブロモフェニルカルバゾール体２の合成手順を以下に示す。 Synthesis example 1
The synthesis of a carbazole-substituted product containing 3-aminopropyltrimethoxysilane (hereinafter abbreviated as APS) as an alkoxysilyl group will be described. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
(1) Synthesis of bromophenylcarbazole body 2 The synthesis procedure of bromophenylcarbazole body 2 is shown below.
Figure JPOXMLDOC01-appb-C000005
Figure JPOXMLDOC01-appb-C000005
　５０ｍｌの二つ口フラスコに化合物１を０．２ｇ［０．９４７ｍｍｏｌ，ｒａｔｉｏ：１．０］、１－ブロモ－４－ヨードベンゼンを０．４ｇ［１．４２ｍｍｏｌ，ｒａｔｉｏ：１．５］、銅を０．１２ｇ［１．８９ｍｍｏｌ，ｒａｔｉｏ：２．０］、炭酸カリウムを０．７９ｇ［５．６８ｍｍｏｌ，ｒａｔｉｏ：６．０］、ＤＭＦ　１０ｍｌを入れ１１０℃で撹拌した。反応が進行したのを確認後、反応溶液をセライト濾過し、水に入れ室温で撹拌しながらｐＨが１以下になるように塩酸を加え、生じた沈殿を吸引濾過した。その後、真空乾燥させ化合物２を得た。収量は０．１２ｇ、収率は３５％であった。 In a 50 ml two-necked flask, 0.2 g [0.947 mmol, ratio: 1.0] of Compound 1 and 0.4 g [1.42 mmol, ratio: 1.5] of 1-bromo-4-iodobenzene, copper 0.12 g [1.89 mmol, ratio: 2.0], potassium carbonate 0.79 g [5.68 mmol, ratio: 6.0], and DMF 10 ml were added and stirred at 110 ° C. After confirming that the reaction had progressed, the reaction solution was filtered through Celite, hydrochloric acid was added so that the pH was 1 or less while stirring at room temperature, and the resulting precipitate was filtered with suction. Thereafter, it was vacuum dried to obtain Compound 2. The yield was 0.12 g, and the yield was 35%.
（２）活性エステル体３の合成
　活性エステル体３の合成手順を以下に示す。 (2) Synthesis of active ester body 3 The synthesis procedure of the active ester body 3 is shown below.
Figure JPOXMLDOC01-appb-C000006
Figure JPOXMLDOC01-appb-C000006
　ナス型フラスコに化合物２を０．１２ｇ（０．３３ｍｍｏｌ，ｒａｔｉｏ：１．０）、Ｎ－ヒドロキシコハク酸イミド０．０４ｇ（０．３６ｍｍｏｌ，ｒａｔｉｏ：１．１）を入れ、ＴＨＦ：クロロホルム＝３：１の３０ｍＬで溶解させた。これに、ＴＨＦ：クロロホルム＝１：４の２０ｍＬに溶解させたＷＳＣＩ・ＨＣｌ（水溶性カルボジイミド塩酸塩）の０．０７ｇ（０．３６ｍｍｏｌ，ｒａｔｉｏ：１．１）を２０分かけてゆっくりと滴下し、滴下後３分間反応させた。反応が進行したことを確認した後、反応液を減圧留去させた。残渣をクロロホルムで溶解し蒸留水で３回洗浄を行った。その後クロロホルム層に無水硫酸マグネシウムを入れ、濾過、減圧留去して、真空乾燥させた。これをシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム１００％）して活性エステル体３を得た。収量は０．０９ｇ、収率は５９％であった。 In an eggplant-shaped flask, 0.12 g (0.33 mmol, ratio: 1.0) of Compound 2 and 0.04 g (0.36 mmol, ratio: 1.1) of N-hydroxysuccinimide were added, and THF: chloroform = 3. 1 was dissolved in 30 mL. To this, 0.07 g (0.36 mmol, ratio: 1.1) of WSCI · HCl (water-soluble carbodiimide hydrochloride) dissolved in 20 mL of THF: chloroform = 1: 4 was slowly added dropwise over 20 minutes. The mixture was reacted for 3 minutes after the dropping. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure. The residue was dissolved in chloroform and washed 3 times with distilled water. Thereafter, anhydrous magnesium sulfate was added to the chloroform layer, filtered, evaporated under reduced pressure, and vacuum dried. This was purified by silica gel column chromatography (Kanto 60N, chloroform 100%) to obtain active ester 3. The yield was 0.09 g, and the yield was 59%.
（３）活性エステル体３とＡＰＳとの反応
　活性エステル体３とＡＰＳとの反応を以下に示す。 (3) Reaction of active ester 3 and APS The reaction of active ester 3 and APS is shown below.
Figure JPOXMLDOC01-appb-C000007
Figure JPOXMLDOC01-appb-C000007
　ナス型フラスコに活性エステル体３を０．０９ｇ（０．１９ｍｍｏｌ，ｒａｔｉｏ：１．０）、３－アミノプロピルトリエトキシシラン０．０４２ｍＬ（０．１９ｍｍｏｌ，ｒａｔｉｏ：１．０）を入れ、ＤＭＦ１０ｍＬで溶解させて室温で反応を開始した。反応が進行したことを確認した後、反応液を減圧留去させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：酢酸エチル＝９．５：０．５）して目的物４（以下、ブロモフェニルカルバゾール－ＡＰＳ体１という）を得た。収量は０．０３ｇ、収率は２７％であった。 In an eggplant-shaped flask, 0.09 g (0.19 mmol, ratio: 1.0) of active ester 3 and 0.042 mL (0.19 mmol, ratio: 1.0) of 3-aminopropyltriethoxysilane were placed, and 10 mL of DMF was added. Once dissolved, the reaction was started at room temperature. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: ethyl acetate = 9.5: 0.5) to obtain the desired product 4 (hereinafter referred to as bromophenylcarbazole-APS isomer 1). The yield was 0.03 g, and the yield was 27%.
合成例２
　アルコキシシリル基として３－メルカプトプロピルトリメトキシシラン（以下、ＭＰＳと略す）を含むカルバゾール置換体の合成について説明する。本合成例では、アルコキシシリル基との結合にチオエステル結合を用いた。以下に反応例を示す。 Synthesis example 2
The synthesis of a carbazole substituted product containing 3-mercaptopropyltrimethoxysilane (hereinafter abbreviated as MPS) as an alkoxysilyl group will be described. In this synthesis example, a thioester bond was used for the bond to the alkoxysilyl group. A reaction example is shown below.
Figure JPOXMLDOC01-appb-C000008
Figure JPOXMLDOC01-appb-C000008
　ナス型フラスコに炭酸カリウムを０．０５３ｇ（０．３８ｍｍｏｌ，ｒａｔｉｏ：２．０）、３－メルカプトプロピルトリエトキシシラン０．０６９ｍＬ（０．２８５ｍｍｏｌ，ｒａｔｉｏ：１．５）を入れ、１,４－Ｄｉｏｘａｎｅ　５ｍＬで溶解させてアルゴン雰囲気下、室温で撹拌した。これに１,４－Ｄｉｏｘａｎｅ　５ｍＬに溶解させた活性エステル体３を０．０９ｇ（０．１９ｍｍｏｌ，ｒａｔｉｏ：１．０）を滴下した。滴下後、８０℃で反応を開始した。反応が進行したことを確認した後、反応液を吸引濾過し減圧留去させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：酢酸エチル＝９．５：０．５）して目的物５（以下、ブロモフェニルカルバゾール－ＡＰＳ体２という）を得た。収量は０.０４ｇ、収率は３５％であった。 In an eggplant-shaped flask, 0.053 g (0.38 mmol, ratio: 2.0) of potassium carbonate and 0.069 mL (0.285 mmol, ratio: 1.5) of 3-mercaptopropyltriethoxysilane were placed. Dioxane was dissolved in 5 mL and stirred at room temperature under an argon atmosphere. To this, 0.09 g (0.19 mmol, ratio: 1.0) of active ester 3 dissolved in 5 mL of 1,4-Dioxane was added dropwise. After dropping, the reaction was started at 80 ° C. After confirming that the reaction had progressed, the reaction solution was suction filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: ethyl acetate = 9.5: 0.5) to obtain the target product 5 (hereinafter referred to as bromophenylcarbazole-APS isomer 2). The yield was 0.04 g and the yield was 35%.
合成例３
　アルコキシシリル基として３－メルカプトプロピルトリメトキシシラン（以下、ＭＰＳと略す）を含むカルバゾール置換体の合成について説明する。本合成例では、アルコキシシリル基との結合にチオエーテル結合を用いた。以下に反応例を示す。 Synthesis example 3
The synthesis of a carbazole substituted product containing 3-mercaptopropyltrimethoxysilane (hereinafter abbreviated as MPS) as an alkoxysilyl group will be described. In this synthesis example, a thioether bond was used for the bond to the alkoxysilyl group. A reaction example is shown below.
Figure JPOXMLDOC01-appb-C000009
Figure JPOXMLDOC01-appb-C000009
　ナス型フラスコに化合物２（本合成例ではブロモフェニルカルバゾール体）を２．０ｇ（５．４６ｍｍｏｌ，ｒａｔｉｏ：１．０）、塩化チオニル０．７９ｍＬ（１０．９ｍｍｏｌ，ｒａｔｏ：２．０）を入れ、クロロホルム　５０ｍＬで溶解させてアルゴン雰囲気下、６０℃で反応を開始した。反応が進行したことを確認した後、反応液を減圧留去した。これに、エタノール１０ｍＬを加え室温で再度反応した。反応が進行したことを確認した後、反応液を減圧留去させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：ヘキサン＝８：２）して化合物２ａを得た。収量は１.４ｇ、収率は６５％であった。 In an eggplant-shaped flask, 2.0 g (5.46 mmol, ratio: 1.0) of compound 2 (bromophenylcarbazole in this synthesis example) and 0.79 mL (10.9 mmol, rato: 2.0) of thionyl chloride were placed. The reaction was started at 60 ° C. in an argon atmosphere after dissolving in 50 mL of chloroform. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure. To this, 10 mL of ethanol was added and reacted again at room temperature. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: hexane = 8: 2) to give compound 2a. The yield was 1.4 g, and the yield was 65%.
　次に、ナス型フラスコに化合物２ａを１．４ｇ（３．５５ｍｍｏｌ，ｒａｔｉｏ：１．０）、水素化ホウ素ナトリウム１．３４ｇ（３５．５ｍｍｏｌ，ｒａｔｏ：１０．０）、を入れ、エタノール　１００ｍＬで溶解させて８０℃で反応を開始した。反応が進行したことを確認した後、反応液を飽和重曹水に入れ室温で撹拌後、吸引濾過、真空乾燥させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：酢酸エチル＝８：２）して化合物６を得た。収量は０.８６ｇ、収率は６９％であった。 Next, 1.4 g (3.55 mmol, ratio: 1.0) of compound 2a and 1.34 g (35.5 mmol, rato: 10.0) of sodium borohydride were placed in an eggplant-shaped flask, and 100 mL of ethanol was added. After dissolution, the reaction was started at 80 ° C. After confirming that the reaction had progressed, the reaction solution was placed in a saturated aqueous sodium bicarbonate solution and stirred at room temperature, followed by suction filtration and vacuum drying. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: ethyl acetate = 8: 2) to give compound 6. The yield was 0.86 g and the yield was 69%.
　次に、ナス型フラスコに化合物６を０．８６ｇ（２．４４ｍｍｏｌ，ｒａｔｉｏ：１．０）、塩化チオニル１．７７ｍＬ（２４．４ｍｍｏｌ，ｒａｔｉｏ：１０．０）を入れ、クロロホルム　５０ｍＬで溶解させて６０℃で反応を開始した。反応が進行したことを確認した後、反応液を水、飽和重曹水の順に洗浄してクロロホルムで抽出した。これに硫酸マグネシウムを入れ、吸引濾過後、減圧留去させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：ヘキサン＝６：４）して化合物７を得た。収量は０.５５ｇ、収率は６０％であった。 Next, 0.86 g (2.44 mmol, ratio: 1.0) of compound 6 and 1.77 mL (24.4 mmol, ratio: 10.0) of thionyl chloride are placed in an eggplant-shaped flask and dissolved in 50 mL of chloroform. The reaction was started at 60 ° C. After confirming that the reaction had progressed, the reaction solution was washed with water and saturated aqueous sodium bicarbonate in this order and extracted with chloroform. Magnesium sulfate was added thereto, and the solution was suction filtered and distilled off under reduced pressure. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: hexane = 6: 4) to obtain Compound 7. The yield was 0.55 g, and the yield was 60%.
　次に、ナス型フラスコに炭酸カリウムを０．０７５ｇ（０．５４ｍｍｏｌ，ｒａｔｉｏ：２．０）、３－メルカプトプロピルトリエトキシシラン０．０９８ｍＬ（０．４０５ｍｍｏｌ，ｒａｔｏ：１．５）、化合物７を０．１ｇ（０．２７ｍｍｏｌ，ｒａｔｉｏ：１．０）を入れ、アセトニトリル　１０ｍＬで溶解させてアルゴン雰囲気下、７５℃で反応を開始した。反応が進行したことを確認した後、反応液を吸引濾過し減圧留去させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：ヘキサン＝８：２）して目的物８（以下、ブロモフェニルカルバゾール－ＡＰＳ体３という）を得た。収量は０.０６３ｇ、収率は４３％であった。 Next, 0.075 g (0.54 mmol, ratio: 2.0) of potassium carbonate, 0.098 mL (0.405 mmol, rato: 1.5) of 3-mercaptopropyltriethoxysilane, and compound 7 were added to the eggplant type flask. 0.1 g (0.27 mmol, ratio: 1.0) was added, dissolved in 10 mL of acetonitrile, and the reaction was started at 75 ° C. under an argon atmosphere. After confirming that the reaction had progressed, the reaction solution was suction filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: hexane = 8: 2) to obtain the desired product 8 (hereinafter referred to as bromophenylcarbazole-APS form 3). The yield was 0.063 g and the yield was 43%.
合成例４
　アルコキシシリル基として３－メチルアミノプロピルトリエトキシシラン（以下、ＭＡＰＳと略す）を含むカルバゾール置換体の合成について説明する。本合成例では、アルコキシシリル基との結合にＮ－メチルアミド結合を用いた。以下に反応例を示す。 Synthesis example 4
The synthesis of a carbazole substituted product containing 3-methylaminopropyltriethoxysilane (hereinafter abbreviated as MAPS) as an alkoxysilyl group will be described. In this synthesis example, an N-methylamide bond was used for the bond to the alkoxysilyl group. A reaction example is shown below.
Figure JPOXMLDOC01-appb-C000010
Figure JPOXMLDOC01-appb-C000010
　ナス型フラスコに化合物３を０．０９ｇ［０．１９ｍｍｏｌ，ｒａｔｉｏ：１．０］、３－メチルアミノプロピルトリエトキシシラン０．０４２ｍｌ［０．１９ｍｍｏｌ，ｒａｔｉｏ：１．０］を入れ、ＤＭＦ　１０ｍＬで溶解させて室温で反応を開始した。反応が進行したことを確認した後、反応液を減圧留去、真空乾燥させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：酢酸エチル＝９．５：０．５）して目的物５（以下、ブロモフェニルカルバゾール－ＭＡＰＳ体という）を得た。収量は０．０３ｇ、収率は２７％であった。 In an eggplant-shaped flask, 0.09 g [0.19 mmol, ratio: 1.0] of compound 3 and 0.042 ml [0.19 mmol, ratio: 1.0] of 3-methylaminopropyltriethoxysilane were placed, and 10 mL of DMF was added. Once dissolved, the reaction was started at room temperature. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure and vacuum dried. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: ethyl acetate = 9.5: 0.5) to obtain the target product 5 (hereinafter referred to as bromophenylcarbazole-MAPS form). The yield was 0.03 g, and the yield was 27%.
合成例５
　カルバゾール置換体としてクロロフェニルカルバゾールを用い、アルコキシシリル基として３－アミノプロピルトリメトキシシランを用いた。本合成例では、アルコキシシリル基との結合にアミド結合を用いた。 Synthesis example 5
Chlorophenylcarbazole was used as the carbazole substituent, and 3-aminopropyltrimethoxysilane was used as the alkoxysilyl group. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
（１）クロロフェニルカルバゾール体６の合成
　クロロフェニルカルバゾール体６の合成手順を以下に示す。 (1) Synthesis of chlorophenylcarbazole body 6 A synthesis procedure of chlorophenylcarbazole body 6 is shown below.
Figure JPOXMLDOC01-appb-C000011
Figure JPOXMLDOC01-appb-C000011
　５０ｍｌの二つ口フラスコに化合物1を０．４ｇ[１．８９ｍｍｏｌ，ｒａｔｉｏ：１．０]、１－クロロ－４－ヨードベンゼンを０．６８ｇ［２．８４ｍｍｏｌ，ｒａｔｉｏ：１．５］、銅を０．２４ｇ［３．７８ｍｍｏｌ，ｒａｔｉｏ：２．０］、炭酸カリウムを１．５６ｇ［１１．３ｍｍｏｌ，ｒａｔｉｏ：６．０］、ＤＭＦ　２０ｍｌを入れ室温で撹拌した。反応が進行したのを確認後、反応溶液をセライト濾過し、水に入れ室温で撹拌しながらｐＨは１以下になるように塩酸を加え、生じた沈殿を吸引濾過した。その後、真空乾燥させ化合物６を得た。収量は０．１８ｇ、収率は３０％であった。 In a 50 ml two-necked flask, 0.4 g of compound 1 [1.89 mmol, ratio: 1.0], 1-chloro-4-iodobenzene 0.68 g [2.84 mmol, ratio: 1.5], copper 0.24 g [3.78 mmol, ratio: 2.0], 1.56 g [11.3 mmol, ratio: 6.0] of potassium carbonate, and 20 ml of DMF were added and stirred at room temperature. After confirming that the reaction had progressed, the reaction solution was filtered through Celite, hydrochloric acid was added so that the pH was 1 or less while stirring at room temperature, and the resulting precipitate was filtered with suction. Thereafter, it was vacuum dried to obtain Compound 6. The yield was 0.18 g, and the yield was 30%.
（２）活性エステル体７の合成
　活性エステル体７の合成手順を以下に示す。 (2) Synthesis of active ester body 7 The synthesis procedure of the active ester body 7 is shown below.
Figure JPOXMLDOC01-appb-C000012
Figure JPOXMLDOC01-appb-C000012
　ナス型フラスコに化合物６を０．１８ｇ［０．５５９ｍｍｏｌ，ｒａｔｉｏ：１．０］、Ｎ－ヒドロキシコハク酸イミド０．０７ｇ［０．６１５ｍｍｏｌ，ｒａｔｉｏ：１．１］を入れ、［ＴＨＦ：クロロホルム＝３：１］３０ｍｌで溶解させた。これに、［ＴＨＦ：クロロホルム＝１：４］３０ｍｌに溶解させたＷＳＣＩ／ＨＣｌ　０．１２ｇ［０．６１５ｍｍｏｌ，ｒａｔｉｏ：１．１］を２０分かけてゆっくりと滴下し、滴下後３時間反応させた。反応が進行したことを確認した後、反応液を減圧留去させた。残渣をクロロホルムで溶解し蒸留水で３回洗浄を行った。その後クロロホルム層に無水硫酸マグネシウムを入れ、濾過、減圧留去して、真空乾燥させた。これをシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム１００％）して目的物７を得た。収量は０．１５ｇ、収率は６４％であった。 In an eggplant-shaped flask, 0.18 g [0.559 mmol, ratio: 1.0] of compound 6 and 0.07 g [0.615 mmol, ratio: 1.1] of N-hydroxysuccinimide were placed, and [THF: chloroform = 3: 1] Dissolved in 30 ml. To this, 0.12 g [0.615 mmol, ratio: 1.1] of WSCI / HCl dissolved in 30 ml of [THF: chloroform = 1: 4] was slowly added dropwise over 20 minutes, followed by reaction for 3 hours. It was. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure. The residue was dissolved in chloroform and washed 3 times with distilled water. Thereafter, anhydrous magnesium sulfate was added to the chloroform layer, filtered, evaporated under reduced pressure, and vacuum dried. This was purified by silica gel column chromatography (Kanto 60N, chloroform 100%) to obtain the intended product 7. The yield was 0.15 g, and the yield was 64%.
（３）活性エステル体７とＡＰＳとの反応
　活性エステル体７とＡＰＳとの反応を以下に示す。 (3) Reaction of active ester 7 and APS The reaction of active ester 7 and APS is shown below.
Figure JPOXMLDOC01-appb-C000013
Figure JPOXMLDOC01-appb-C000013
　ナス型フラスコに化合物７を０．１５ｇ［０．３５８ｍｍｏｌ，ｒａｔｉｏ：１．０］、３－アミノプロピルトリエトキシシラン０．０９１ｍｌ［０．３９４ｍｍｏｌ，ｒａｔｉｏ：１．１］を入れ、ＤＭＦ　１０ｍｌで溶解させて室温で反応を開始した。反応が進行したことを確認した後、反応液を減圧留去、真空乾燥させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：酢酸エチル＝９．５：０．５）して目的物８（以下、クロロフェニルカルバゾール－ＡＰＳ体１という）を得た。収量は０．０６４ｇ、収率は３４％であった。 Add 0.15 g [0.358 mmol, ratio: 1.0] of compound 7 and 0.091 ml [0.394 mmol, ratio: 1.1] of 3-aminopropyltriethoxysilane to an eggplant-shaped flask and dissolve in 10 ml of DMF. The reaction was started at room temperature. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure and vacuum dried. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: ethyl acetate = 9.5: 0.5) to obtain the target product 8 (hereinafter referred to as chlorophenylcarbazole-APS isomer 1). The yield was 0.064 g, and the yield was 34%.
合成例６
　アルコキシシリル基として３－メチルアミノプロピルトリエトキシシランを含むクロロカルバゾール体の合成について説明する。本合成例では、アルコキシシリル基との結合にＮ－メチルアミド結合を用いた。以下に反応例を示す。 Synthesis Example 6
The synthesis of a chlorocarbazole compound containing 3-methylaminopropyltriethoxysilane as an alkoxysilyl group will be described. In this synthesis example, an N-methylamide bond was used for the bond to the alkoxysilyl group. A reaction example is shown below.
Figure JPOXMLDOC01-appb-C000014
Figure JPOXMLDOC01-appb-C000014
　ナス型フラスコに化合物７を０．１ｇ［０．２３９ｍｍｏｌ，ｒａｔｉｏ：１．０］、３－メチルアミノメチルプロピルトリエトキシシラン０．０６５ｍｌ［０．２３６ｍｍｏｌ，ｒａｔｉｏ：１．１］を入れ、ＤＭＦ　７ｍｌで溶解させて室温で反応を開始した。反応が進行したことを確認した後、反応液を減圧留去、真空乾燥させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：酢酸エチル＝９：１）して目的物９（以下、クロロフェニルカルバゾール－ＭＡＰＳ体という）を得た。収量は０．０３８ｇ、収率は３０％であった。 In an eggplant-shaped flask, 0.1 g [0.239 mmol, ratio: 1.0] of Compound 7 and 0.065 ml [0.236 mmol, ratio: 1.1] of 3-methylaminomethylpropyltriethoxysilane were placed, and 7 ml of DMF was added. And the reaction was started at room temperature. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure and vacuum dried. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: ethyl acetate = 9: 1) to obtain the desired product 9 (hereinafter referred to as chlorophenylcarbazole-MAPS form). The yield was 0.038 g, and the yield was 30%.
合成例７
　カルバゾール置換体としてメチルフェニルカルバゾール体を用い、アルコキシシリル基として３－アミノプロピルトリメトキシシランを用いた。本合成例では、アルコキシシリル基との結合にアミド結合を用いた。 Synthesis example 7
Methylphenylcarbazole was used as the carbazole substituent, and 3-aminopropyltrimethoxysilane was used as the alkoxysilyl group. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
（１）メチルフェニルカルバゾール体１０の合成
　メチルフェニルカルバゾール体１０の合成手順を以下に示す。 (1) Synthesis of methylphenylcarbazole body 10 A synthesis procedure of methylphenylcarbazole body 10 is shown below.
Figure JPOXMLDOC01-appb-C000015
Figure JPOXMLDOC01-appb-C000015
　５０ｍｌの二つ口フラスコに化合物１を０．４ｇ［１．８９ｍｍｏｌ，ｒａｔｉｏ：１．０］、１－クロロ－４－ヨードベンゼンを０．６２ｇ［２．８４ｍｍｏｌ，ｒａｔｉｏ：１．５］、銅を０．２４ｇ［３．７８ｍｍｏｌ，ｒａｔｉｏ：２．０］、炭酸カリウムを１．５６ｇ［１１．３ｍｍｏｌ，ｒａｔｉｏ：６．０］、ＤＭＦ　２０ｍｌを入れ室温で撹拌した。反応が進行したのを確認後、反応溶液をセライト濾過し、水に入れ室温で撹拌しながらｐＨが１以下になるように塩酸を加え、生じた沈殿を吸引濾過した。その後、真空乾燥させ化合物１０を得た。収量は０．２１ｇ、収率は３７％であった。 In a 50 ml two-necked flask, 0.4 g of compound 1 [1.89 mmol, ratio: 1.0], 0.62 g of 1-chloro-4-iodobenzene [2.84 mmol, ratio: 1.5], copper 0.24 g [3.78 mmol, ratio: 2.0], 1.56 g [11.3 mmol, ratio: 6.0] of potassium carbonate, and 20 ml of DMF were added and stirred at room temperature. After confirming that the reaction had progressed, the reaction solution was filtered through Celite, hydrochloric acid was added so that the pH was 1 or less while stirring at room temperature, and the resulting precipitate was filtered with suction. Thereafter, it was vacuum dried to obtain Compound 10. The yield was 0.21 g and the yield was 37%.
（２）活性エステル体１１の合成
　活性エステル体１１の合成手順を以下に示す。 (2) Synthesis of active ester 11 The procedure for synthesizing the active ester 11 is shown below.
Figure JPOXMLDOC01-appb-C000016
Figure JPOXMLDOC01-appb-C000016
（３）活性エステル体１１とＡＰＳとの反応
　活性エステル体１１とＡＰＳとの反応を以下に示す。 (3) Reaction of active ester 11 and APS The reaction of active ester 11 and APS is shown below.
Figure JPOXMLDOC01-appb-C000017
Figure JPOXMLDOC01-appb-C000017
　ナス型フラスコに化合物１１を０．１ｇ［０．２５１ｍｍｏｌ，ｒａｔｉｏ：１．０］、３－アミノプロピルトリエトキシシラン０．０６４ｍｌ［０．２７６ｍｍｏｌ，ｒａｔｉｏ：１．１］を入れ、ＤＭＦ　７ｍｌで溶解させて室温で反応を開始した。反応が進行したことを確認した後、反応液を減圧留去、真空乾燥させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：酢酸エチル＝９．５：０．５）して目的物１２（以下、メチルフェニルカルバゾール－ＡＰＳ体という）を得た。収量は０．０４９ｇ、収率は３９％であった。 In an eggplant-shaped flask, 0.1 g [0.251 mmol, ratio: 1.0] and 0.064 ml [0.276 mmol, ratio: 1.1] of 3-aminopropyltriethoxysilane were placed and dissolved in 7 ml of DMF. The reaction was started at room temperature. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure and vacuum dried. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: ethyl acetate = 9.5: 0.5) to obtain the desired product 12 (hereinafter referred to as methylphenylcarbazole-APS form). The yield was 0.049 g, and the yield was 39%.
合成例８
　アルコキシシリル基として３－メチルアミノプロピルトリエトキシシランを含むメチルフェニルカルバゾールの合成について説明する。本合成例では、アルコキシシリル基との結合にＮ－メチルアミド結合を用いた。以下に反応例を示す。 Synthesis example 8
The synthesis of methylphenylcarbazole containing 3-methylaminopropyltriethoxysilane as an alkoxysilyl group will be described. In this synthesis example, an N-methylamide bond was used for the bond to the alkoxysilyl group. A reaction example is shown below.
Figure JPOXMLDOC01-appb-C000018
Figure JPOXMLDOC01-appb-C000018
　ナス型フラスコに化合物１１を０．１ｇ［０．２５１ｍｍｏｌ，ｒａｔｉｏ：１．０］、３－アミノメチルプロピルトリエトキシシラン０．０６８ｍｌ［０．２７６ｍｍｏｌ，ｒａｔｉｏ：１．１］を入れ、ＤＭＦ　７ｍｌで溶解させて室温で反応を開始した。反応が進行したことを確認した後、反応液を減圧留去、真空乾燥させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：酢酸エチル＝９：１）して目的物１３（以下、メチルフェニルカルバゾール－ＭＡＰＳ体という）を得た。収量は０．０４５ｇ、収率は３５％であった。 In an eggplant-shaped flask, 0.1 g [0.251 mmol, ratio: 1.0] of compound 11 and 0.068 ml [0.276 mmol, ratio: 1.1] of 3-aminomethylpropyltriethoxysilane were placed, and 7 ml of DMF was added. Once dissolved, the reaction was started at room temperature. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure and vacuum dried. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: ethyl acetate = 9: 1) to obtain the desired product 13 (hereinafter referred to as methylphenylcarbazole-MAPS form). The yield was 0.045 g, and the yield was 35%.
合成例９
　アルコキシシリル基として３－アミノプロピルトリエトキシシランを含むチオナフテン置換体の合成について説明する。本合成例では、アルコキシシリル基との結合にアミド結合を用いた。 Synthesis Example 9
The synthesis of a thionaphthene substituted product containing 3-aminopropyltriethoxysilane as an alkoxysilyl group will be described. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
（１）活性エステル体１５の合成
　活性エステル体１５の合成手順を以下に示す。 (1) Synthesis of active ester 15 The procedure for synthesizing the active ester 15 is shown below.
Figure JPOXMLDOC01-appb-C000019
Figure JPOXMLDOC01-appb-C000019
　ナス型フラスコに化合物１４を０．２ｇ［１．１２ｍｍｏｌ，ｒａｔｉｏ：１．０］、Ｎ－ヒドロキシコハク酸イミド０．１４ｇ［１．２３ｍｍｏｌ，ｒａｉｏ：１．１］を入れ、［ＴＨＦ：クロロホルム＝３：１］の３０ｍｌで溶解させた。これに、［ＴＨＦ：クロロホルム＝１：４］３０ｍｌに溶解させたＷＳＣＩ・ＨＣｌ　０．２４ｇ［１．２３ｍｍｏｌ，ｒａｔｉｏ：１．１］を２０分かけてゆっくりと滴下し、滴下後３時間反応させた。反応が進行したことを確認した後、反応液を減圧留去させた。残渣をクロロホルムで溶解し蒸留水で３回洗浄を行った。その後クロロホルム層に無水硫酸マグネシウムを入れ、濾過、減圧留去して、真空乾燥させた。これをシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム１００％）して目的物１５を得た。収量は０．１３ｇ、収率は４２％であった。 In an eggplant-shaped flask, 0.2 g [1.12 mmol, ratio: 1.0] of compound 14 and 0.14 g [1.23 mmol, ratio: 1.1] of N-hydroxysuccinimide were placed, and [THF: chloroform = 3: 1] was dissolved in 30 ml. To this, 0.24 g [1.23 mmol, ratio: 1.1] of WSCI · HCl dissolved in 30 ml of [THF: chloroform = 1: 4] was slowly added dropwise over 20 minutes, followed by reaction for 3 hours. It was. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure. The residue was dissolved in chloroform and washed 3 times with distilled water. Thereafter, anhydrous magnesium sulfate was added to the chloroform layer, filtered, evaporated under reduced pressure, and vacuum dried. This was purified by silica gel column chromatography (Kanto 60N, chloroform 100%) to give the intended product 15. The yield was 0.13 g, and the yield was 42%.
（２）活性エステル体１５とＡＰＳとの反応
　活性エステル体１５とＡＰＳとの反応を以下に示す。 (2) Reaction of active ester 15 and APS The reaction of active ester 15 and APS is shown below.
Figure JPOXMLDOC01-appb-C000020
Figure JPOXMLDOC01-appb-C000020
　ナス型フラスコに化合物１５を０．１ｇ[０．３６３ｍｍｏｌ，ｒａｔｉｏ：１．０]、３－アミノプロピルトリエトキシシラン０．０９３ｍｌ［０．３９９ｍｍｏｌ，ｒａｔｉｏ：１．１］を入れ、ＤＭＦ　７ｍｌで溶解させて室温で反応を開始した。反応が進行したことを確認した後、反応液を減圧留去、真空乾燥させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム：ヘキサン＝９：１）して目的物１６（以下、チオナフテン－ＡＰＳ体という）を得た。収量は０．０５６ｇ、収率は４０％であった。 In an eggplant-shaped flask, 0.1 g [0.363 mmol, ratio: 1.0] of compound 15 and 0.093 ml [0.399 mmol, ratio: 1.1] of 3-aminopropyltriethoxysilane were placed and dissolved in 7 ml of DMF. The reaction was started at room temperature. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure and vacuum dried. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform: hexane = 9: 1) to obtain the target product 16 (hereinafter referred to as thionaphthene-APS form). The yield was 0.056 g, and the yield was 40%.
合成例１０
　アルコキシシリル基として３－アミノプロピルトリエトキシシランを含むインドール置換体の合成について説明する。本合成例では、アルコキシシリル基との結合にアミド結合を用いた。 Synthesis Example 10
The synthesis of an indole substitution product containing 3-aminopropyltriethoxysilane as an alkoxysilyl group will be described. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
（１）活性エステル体１８の合成
　活性エステル体１８の合成手順を以下に示す。 (1) Synthesis of active ester form 18 The synthesis procedure of the active ester form 18 is shown below.
Figure JPOXMLDOC01-appb-C000021
Figure JPOXMLDOC01-appb-C000021
　ナス型フラスコに化合物１７を０．２ｇ［１．２４ｍｍｏｌ，ｒａｔｉｏ：１．０］、Ｎ－ヒドロキシコハク酸イミド０．１５６ｇ［１．３６ｍｍｏｌ，ｒａｉｏ：１．１］を入れ、［ＴＨＦ：クロロホルム＝３：１］　３０ｍｌで溶解させた。これに、［ＴＨＦ：クロロホルム＝１：４］　３０ｍｌに溶解させたＷＳＣＩ・ＨＣｌ　０．２６ｇ［１．３６ｍｍｏｌ，ｒａｔｉｏ：１．１］を２０分かけてゆっくりと滴下し、滴下後３時間反応させた。反応が進行したことを確認した後、反応液を減圧留去させた。残渣をクロロホルムで溶解し蒸留水で３回洗浄を行った。その後クロロホルム層に無水硫酸マグネシウムを入れ、濾過、減圧留去して、真空乾燥させた。これをシリカゲルカラムクロマトグラフィー精製（Ｋａｎｏ　６０Ｎ，クロロホルム１００％）して目的物１８を得た。収量は０．１２ｇ、収率は３７％であった。 In an eggplant-shaped flask, 0.2 g [1.24 mmol, ratio: 1.0] of Compound 17 and 0.156 g [1.36 mmol, ratio: 1.1] of N-hydroxysuccinimide were placed, and [THF: chloroform = 3: 1] Dissolved in 30 ml. [THF: chloroform = 1: 4] WSCI · HCl 0.26 g [1.36 mmol, ratio: 1.1] dissolved in 30 ml was slowly added dropwise over 20 minutes, and the mixture was reacted for 3 hours after the addition. It was. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure. The residue was dissolved in chloroform and washed 3 times with distilled water. Thereafter, anhydrous magnesium sulfate was added to the chloroform layer, filtered, evaporated under reduced pressure, and vacuum dried. This was purified by silica gel column chromatography (Kano 60N, chloroform 100%) to obtain the target product 18. The yield was 0.12 g, and the yield was 37%.
（２）活性エステル体１８とＡＰＳとの反応
　活性エステル体１８とＡＰＳとの反応を以下に示す。 (2) Reaction between active ester 18 and APS The reaction between active ester 18 and APS is shown below.
Figure JPOXMLDOC01-appb-C000022
Figure JPOXMLDOC01-appb-C000022
　ナス型フラスコに化合物１８を０．１ｇ［０．３８７ｍｍｏｌ，ｒａｔｉｏ：１．０］、３－アミノプロピルトリエトキシシラン０．０９９ｍｌ［０．４２６ｍｍｏｌ，ｒａｔｉｏ：１．１］を入れ、ＤＭＦ　７ｍｌで溶解させて室温で反応を開始した。反応が進行したことを確認した後、反応液を減圧留去、真空乾燥させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム１００％）して目的物１９（以下、インドール－ＡＰＳ体という）を得た。収量は０．０３８ｇ、収率は２７％であった。 In an eggplant-shaped flask, 0.1 g [0.387 mmol, ratio: 1.0] of compound 18 and 0.099 ml [0.426 mmol, ratio: 1.1] of 3-aminopropyltriethoxysilane were placed and dissolved in 7 ml of DMF. The reaction was started at room temperature. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure and vacuum dried. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform 100%) to obtain the desired product 19 (hereinafter referred to as indole-APS form). The yield was 0.038 g, and the yield was 27%.
合成例１１
　アルコキシシリル基として３－アミノプロピルトリエトキシシランを含むジベンゾフラン置換体の合成について説明する。本合成例では、アルコキシシリル基との結合にアミド結合を用いた。 Synthesis Example 11
The synthesis of a dibenzofuran substituted product containing 3-aminopropyltriethoxysilane as an alkoxysilyl group will be described. In this synthesis example, an amide bond was used for the bond to the alkoxysilyl group.
（１）活性エステル体２１の合成
　活性エステル体２１の合成手順を以下に示す。 (1) Synthesis of active ester 21 The procedure for synthesizing the active ester 21 is shown below.
Figure JPOXMLDOC01-appb-C000023
Figure JPOXMLDOC01-appb-C000023
　ナス型フラスコに化合物２０を０．２ｇ［０．９４２ｍｍｏｌ，ｒａｔｉｏ：１．０］Ｎ－ヒドロキシコハク酸イミド　０．１１９ｇ［１．０３ｍｍｏｌ，ｒａｔｉｏ：１．１］を入れ、［ＴＨＦ：クロロホルム＝３：１］　３０ｍｌで溶解させた。これに、［ＴＨＦ：クロロホルム＝１：４］　３０ｍｌに溶解させたＷＳＣＩ・ＨＣｌ　０．１９８ｇ［１．０３ｍｍｏｌ，ｒａｔｉｏ：１．１］を２０分かけてゆっくりと滴下し、滴下後３時間反応させた。反応が進行したことを確認した後、反応液を減圧留去させた。残渣をクロロホルムで溶解し蒸留水で３回洗浄を行った。その後クロロホルム層に無水硫酸マグネシウムを入れ、濾過、減圧留去して、真空乾燥させた。これをシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム１００％）して目的物２１を得た。収量は０．１３ｇ、収率は４５％であった。 0.2 g [0.942 mmol, ratio: 1.0] N-hydroxysuccinimide 0.119 g [1.03 mmol, ratio: 1.1] was placed in an eggplant-shaped flask, and [THF: chloroform = 3]. : 1] 30 ml was dissolved. To this, 0.198 g [1.03 mmol, ratio: 1.1] of WSCI · HCl dissolved in 30 ml of [THF: chloroform = 1: 4] was slowly added dropwise over 20 minutes, followed by reaction for 3 hours. It was. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure. The residue was dissolved in chloroform and washed 3 times with distilled water. Thereafter, anhydrous magnesium sulfate was added to the chloroform layer, filtered, evaporated under reduced pressure, and vacuum dried. This was purified by silica gel column chromatography (Kanto 60N, chloroform 100%) to give the intended product 21. The yield was 0.13 g, and the yield was 45%.
（２）活性エステル体２１とＡＰＳとの反応
　活性エステル体２１とＡＰＳとの反応を以下に示す。 (2) Reaction of active ester 21 and APS The reaction of active ester 21 and APS is shown below.
Figure JPOXMLDOC01-appb-C000024
Figure JPOXMLDOC01-appb-C000024
　ナス型フラスコに化合物２１を０．１ｇ［０．３２３ｍｍｏｌ，ｒａｔｉｏ：１．０］、３－アミノプロピルトリエトキシシラン０．０８３ｍｌ［０．３５５ｍｍｏｌ，ｒａｔｉｏ：１．１］を入れ、ＤＭＦ　７ｍｌで溶解させて室温で反応を開始した。反応が進行したことを確認した後、反応液を減圧留去、真空乾燥させた。残渣をシリカゲルカラムクロマトグラフィー精製（Ｋａｎｔｏ　６０Ｎ，クロロホルム１００％）して目的物２２（以下、ジベンゾフラン－ＡＰＳ体という）を得た。収量は０．０５ｇ、収率は３７％であった。 In an eggplant-shaped flask, 0.1 g [0.323 mmol, ratio: 1.0] of compound 21 and 0.083 ml [0.355 mmol, ratio: 1.1] of 3-aminopropyltriethoxysilane were placed and dissolved in 7 ml of DMF. The reaction was started at room temperature. After confirming that the reaction had progressed, the reaction solution was distilled off under reduced pressure and vacuum dried. The residue was purified by silica gel column chromatography (Kanto 60N, chloroform 100%) to obtain the desired product 22 (hereinafter referred to as dibenzofuran-APS form). The yield was 0.05 g and the yield was 37%.
（紫外線退光試験）
　クロロホルムに溶解させたブロモフェニルカルバゾール－ＡＰＳ体１をスライドガラス上に垂らし、乾燥させ膜状のサンプルを作製した。作製したサンプルに紫外線を照射して、１時間おきにデジタルカメラまたは蛍光顕微鏡でサンプルの退光を観察した。 (Ultraviolet light fading test)
Bromophenylcarbazole-APS body 1 dissolved in chloroform was hung on a slide glass and dried to prepare a film sample. The prepared sample was irradiated with ultraviolet rays, and the fading of the sample was observed with a digital camera or a fluorescence microscope every hour.
　紫外線退光試験には、以下の装置を用いた。
紫外線ランプ：アズワンＳＬＵＶ－４、照射波長　３６５ｎｍ
デジタルカメラ：ＲＩＣＯＨ　ＣＸ４
蛍光顕微鏡：ＯＬＹＭＰＵＳ　ＢＸ５０
励起フィルター：ＥＴ３９５／４０Ｘ
※ダイクロイックミラー　Ｔ４７０ｐｘｒ
吸収フィルター：ＥＴ５２５／２０ｍ The following apparatus was used for the ultraviolet light fading test.
Ultraviolet lamp: ASONE SLUV-4, irradiation wavelength 365 nm
Digital camera: RICOH CX4
Fluorescence microscope: OLYMPUS BX50
Excitation filter: ET395 / 40X
* Dichroic mirror T470pxr
Absorption filter: ET525 / 20m
　顕微鏡撮影条件は、以下の通りである。
　露出時間：１．０ｓｅｃ
ＩＳＯ感度：２００
対物レンズ：１０ｘ The microscope photographing conditions are as follows.
Exposure time: 1.0 sec
ISO sensitivity: 200
Objective lens: 10x
（結果）
　図１に、紫外線照射前と紫外線照射１時間～６時間後のデジタルカメラによる観察画像を示す。紫外線照射６時間後でも退光は認められなかった。また、図２と図３に蛍光顕微鏡による観察画像を示す。図２と図３では、観察箇所が異なる。蛍光顕微鏡で観察した場合でも、紫外線照射６時間後で退光は認められなかった。なお、ブロモフェニルカルバゾール－ＡＰＳ体２と３についても同様の試験を行ったが、紫外線照射６時間後で退光は認められなかった。 (result)
FIG. 1 shows images observed by a digital camera before UV irradiation and after 1 to 6 hours of UV irradiation. No fading was observed even after 6 hours of UV irradiation. 2 and 3 show images observed with a fluorescence microscope. FIG. 2 and FIG. 3 differ in the observation location. Even when observed with a fluorescence microscope, no fading was observed after 6 hours of UV irradiation. A similar test was conducted on bromophenylcarbazole-APS bodies 2 and 3, but no photoregression was observed after 6 hours of ultraviolet irradiation.
　また、図４～図８は蛍光顕微鏡による観察画像であり、図４は合成例４のブロモフェニルカルバゾール－ＭＡＰＳ体、図５は合成例５のクロロフェニルカルバゾール体－ＡＰＳ体、図６は合成例６のクロロフェニルカルバゾール－ＭＡＰＳ体、図７は合成例７のメチルフェニルカルバゾール－ＡＰＳ体、図８は合成例８のメチルフェニルカルバゾール－ＭＡＰＳ体の画像である。いずれにおいても紫外線照射６時間後で退光は認められなかった。また、合成例９～１１についても同様の効果が認められた。このように、本発明のアルコキシシリル基含有燐光色素は、室温、固体状態で燐光を発光することが可能であることを確認した。 4 to 8 are images observed with a fluorescence microscope, FIG. 4 is a bromophenylcarbazole-MAPS form of Synthesis Example 4, FIG. 5 is a chlorophenylcarbazole form-APS form of Synthesis Example 5, and FIG. 7 is an image of the methylphenylcarbazole-MAPS form of Synthesis Example 7, and FIG. 8 is an image of the methylphenylcarbazole-MAPS form of Synthesis Example 8. In any case, no fading was observed after 6 hours of ultraviolet irradiation. Similar effects were also observed in Synthesis Examples 9-11. As described above, it was confirmed that the alkoxysilyl group-containing phosphorescent dye of the present invention can emit phosphorescence at room temperature in a solid state.
　従来、有機燐光色素は、室温での発光効率が非常に低く、室温、固体状態で発光するものはほとんど知られておらず、従来の燐光色素含有シリカ粒子は、室温、固体状態で発光しない。これに対し、本発明のアルコキシシリル基含有燐光色素は、室温、固体状態で燐光を発光することから、燐光色素を含む新たなナノ粒子として多くの用途が期待できる。 Conventionally, organic phosphorescent dyes have a very low luminous efficiency at room temperature, and few are known to emit light at room temperature in a solid state. Conventional phosphorescent dye-containing silica particles do not emit light at room temperature in a solid state. On the other hand, since the alkoxysilyl group-containing phosphorescent dye of the present invention emits phosphorescence at room temperature in a solid state, many uses can be expected as new nanoparticles containing the phosphorescent dye.

Claims (4)

  1. 　一般式Ｘ―Ｙ－Ｑ－Ｚ－Ｓｉ（Ｒ１）ｎ（ＯＲ２）３－ｎで表され、Ｘが有機燐光色素、Ｙが直接結合あるいは－（ＣＨ２）ｐ－（ｐは１から１０の整数）または－（Ｏ－ＣＨ２ＣＨ２）ｑ－（ｑは１から１０の整数）であり、Ｑはアミド結合、エーテル結合、チオエーテル結合、チオエステル結合、チオウレア結合、ジスルフィド結合およびポリオキシエチレン結合から選択される少なくとも１種の結合であり、Ｚは－（ＣＨ２）ｍ－または－（ＣＨ２）２ＮＨ（ＣＨ２）３－であり、Ｒ１とＲ２は炭素数１から４のアルキル基であり、ｎは０または１であり、ｍは１から１０の整数であるアルコキシシリル基含有燐光色素。 Represented by the general formula X—Y—Q—Z—Si (R 1 ) n (OR 2 ) 3-n , where X is an organic phosphorescent dye and Y is a direct bond or — (CH 2 ) p — (p is from 1 Q is an integer of 10) or — (O—CH 2 CH 2 ) q — (q is an integer of 1 to 10), and Q is an amide bond, an ether bond, a thioether bond, a thioester bond, a thiourea bond, a disulfide bond, and a polyoxy At least one bond selected from ethylene bonds, Z is — (CH 2 ) m — or — (CH 2 ) 2 NH (CH 2 ) 3 —, and R 1 and R 2 are each from 1 to C carbon atoms An alkoxysilyl group-containing phosphorescent dye which is an alkyl group of 4, n is 0 or 1, and m is an integer of 1 to 10.
  2. 　前記有機燐光色素が、置換または無置換のカルバゾール、置換または無置換のジベンゾフラン、置換または無置換のチオナフテン、置換または無置換のインドール、置換または無置換の１，３，５－トリアジンから成る群から選択される少なくとも１種の化合物である、請求項１記載のアルコキシシリル基含有燐光色素。 The organic phosphorescent dye is selected from the group consisting of substituted or unsubstituted carbazole, substituted or unsubstituted dibenzofuran, substituted or unsubstituted thionaphthene, substituted or unsubstituted indole, substituted or unsubstituted 1,3,5-triazine. The alkoxysilyl group-containing phosphorescent dye according to claim 1, which is at least one selected compound.
  3. 　前記のカルバゾールが、Ｎ－置換カルバゾールである、請求項２記載のアルコキシシリル基含有燐光色素。 The alkoxysilyl group-containing phosphorescent dye according to claim 2, wherein the carbazole is N-substituted carbazole.
  4. 　請求項１記載のアルコキシシリル基含有燐光色素の製造方法であって、
    　前記有機燐光色素が、スクシンイミジルエステル基、アルコラート基、アミノ基、メルカプト基、ハロゲン化アルキル基および末端ヒドロキシ基含有ポリオキシエチレン基からなる群から選択される１種の反応性基を有し、前記有機燐光色素とシランカップリング剤を混合する工程を含む、該製造方法。     A method for producing an alkoxysilyl group-containing phosphorescent dye according to claim 1,
    The organic phosphorescent dye has one reactive group selected from the group consisting of a succinimidyl ester group, an alcoholate group, an amino group, a mercapto group, a halogenated alkyl group, and a terminal hydroxy group-containing polyoxyethylene group. The production method comprising a step of mixing the organic phosphorescent dye and a silane coupling agent.
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