CN111269185A - Benzimidazole based on dicarboxylic acid and preparation and application thereof - Google Patents
Benzimidazole based on dicarboxylic acid and preparation and application thereof Download PDFInfo
- Publication number
- CN111269185A CN111269185A CN201811480165.8A CN201811480165A CN111269185A CN 111269185 A CN111269185 A CN 111269185A CN 201811480165 A CN201811480165 A CN 201811480165A CN 111269185 A CN111269185 A CN 111269185A
- Authority
- CN
- China
- Prior art keywords
- dicarboxylic acid
- benzimidazole
- solution
- reaction
- serum albumin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 title claims description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 7
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000012065 filter cake Substances 0.000 claims description 28
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 18
- 229940098773 bovine serum albumin Drugs 0.000 claims description 18
- 238000005406 washing Methods 0.000 claims description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 10
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 8
- 150000001991 dicarboxylic acids Chemical class 0.000 claims description 8
- 239000007850 fluorescent dye Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 7
- 238000000967 suction filtration Methods 0.000 claims description 7
- 238000001215 fluorescent labelling Methods 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 239000002131 composite material Substances 0.000 claims description 3
- 239000003550 marker Substances 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 238000000108 ultra-filtration Methods 0.000 claims description 3
- 229940041181 antineoplastic drug Drugs 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 238000006482 condensation reaction Methods 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims description 2
- 238000006297 dehydration reaction Methods 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 230000000507 anthelmentic effect Effects 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 claims 1
- 238000005260 corrosion Methods 0.000 claims 1
- 230000007797 corrosion Effects 0.000 claims 1
- 238000003234 fluorescent labeling method Methods 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 8
- 150000001556 benzimidazoles Chemical class 0.000 abstract description 8
- 239000003513 alkali Substances 0.000 abstract description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 abstract 2
- QQHJDPROMQRDLA-UHFFFAOYSA-N hexadecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCC(O)=O QQHJDPROMQRDLA-UHFFFAOYSA-N 0.000 description 9
- HQHCYKULIHKCEB-UHFFFAOYSA-N tetradecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCC(O)=O HQHCYKULIHKCEB-UHFFFAOYSA-N 0.000 description 7
- TVIDDXQYHWJXFK-UHFFFAOYSA-N dodecanedioic acid Chemical compound OC(=O)CCCCCCCCCCC(O)=O TVIDDXQYHWJXFK-UHFFFAOYSA-N 0.000 description 6
- 239000007810 chemical reaction solvent Substances 0.000 description 5
- QCNWZROVPSVEJA-UHFFFAOYSA-N Heptadecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCCC(O)=O QCNWZROVPSVEJA-UHFFFAOYSA-N 0.000 description 4
- BTZVDPWKGXMQFW-UHFFFAOYSA-N Pentadecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCC(O)=O BTZVDPWKGXMQFW-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- BNJOQKFENDDGSC-UHFFFAOYSA-N octadecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCCCC(O)=O BNJOQKFENDDGSC-UHFFFAOYSA-N 0.000 description 4
- JJOJFIHJIRWASH-UHFFFAOYSA-N icosanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCCCCCC(O)=O JJOJFIHJIRWASH-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FKUPPRZPSYCDRS-UHFFFAOYSA-N Cyclopentadecanolide Chemical compound O=C1CCCCCCCCCCCCCCO1 FKUPPRZPSYCDRS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000005536 corrosion prevention Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- DXNCZXXFRKPEPY-UHFFFAOYSA-N tridecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCC(O)=O DXNCZXXFRKPEPY-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- RHXSYTACTOMVLJ-UHFFFAOYSA-N 1H-benzimidazole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=NC2=C1 RHXSYTACTOMVLJ-UHFFFAOYSA-N 0.000 description 1
- CJPNOLIZCWDHJK-UHFFFAOYSA-N 2-Pentadecanone Chemical compound CCCCCCCCCCCCCC(C)=O CJPNOLIZCWDHJK-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- XGSGTQJIWNAGCC-UHFFFAOYSA-N CCCCCCCCCCCCCCCCCC(C1=NC2=CC=CC=C2N1)C(=O)O Chemical compound CCCCCCCCCCCCCCCCCC(C1=NC2=CC=CC=C2N1)C(=O)O XGSGTQJIWNAGCC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 229940122236 Histamine receptor antagonist Drugs 0.000 description 1
- 101100280298 Homo sapiens FAM162A gene Proteins 0.000 description 1
- 101100537375 Homo sapiens TMEM107 gene Proteins 0.000 description 1
- 241000972155 Moschus Species 0.000 description 1
- ALHUZKCOMYUFRB-OAHLLOKOSA-N Muscone Chemical compound C[C@@H]1CCCCCCCCCCCCC(=O)C1 ALHUZKCOMYUFRB-OAHLLOKOSA-N 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 102100023788 Protein FAM162A Human genes 0.000 description 1
- 102100036728 Transmembrane protein 107 Human genes 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 229940125687 antiparasitic agent Drugs 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- -1 benzimidazole compound Chemical class 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000011162 downstream development Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- YAQXGBBDJYBXKL-UHFFFAOYSA-N iron(2+);1,10-phenanthroline;dicyanide Chemical compound [Fe+2].N#[C-].N#[C-].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1 YAQXGBBDJYBXKL-UHFFFAOYSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- ALHUZKCOMYUFRB-UHFFFAOYSA-N muskone Natural products CC1CCCCCCCCCCCCC(=O)C1 ALHUZKCOMYUFRB-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/16—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/76—Albumins
- C07K14/765—Serum albumin, e.g. HSA
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- 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
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- 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
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Analytical Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Optics & Photonics (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention provides a binary carboxylic acid-based benzimidazole and a preparation method and application thereof, wherein the binary carboxylic acid-based benzimidazole has the following structural general formula:
Description
Technical Field
The invention belongs to the field of organic chemistry, and particularly relates to carboxyl benzimidazole and a preparation method and application thereof.
Background
The benzimidazole compound is a heterocyclic compound containing two nitrogen atoms, and the structural formula of the compound is as follows:
the structure can form hydrogen bond with enzyme and receptor in organism, coordinate with metal ion, and generate hydrophobic-hydrophobic and pi-pi interaction, so it has multiple biological physiological activities. The benzimidazole and the derivative thereof have pharmacological effects of expelling parasites, sterilizing, resisting cancers and the like, and are widely applied to the fields of high-energy density compounds, high-performance composite materials, metal corrosion prevention, photosensitive fluorescent materials and the like. Especially in the medical field: as histamine receptor antagonists, proton pump inhibitors, antihypertensive agents, antiparasitic agents, antibacterial agents, antifungal agents, antiviral agents, anticancer agents, analgesic agents, etc., they also exhibit excellent effects in terms of anti-inflammatory agents, analgesic agents, enzyme inhibitors, antispasmodic agents, receptor agonists, etc. The research and development of novel benzimidazole structural fragment-containing medicines are the key development directions of future benzimidazole medicine research, and through continuous screening, the benzimidazole structural fragment-containing medicines are expected to play an important role in the fields of cancer resistance, AIDS resistance and the like which are relatively troublesome to treat.
Disclosure of Invention
Aiming at the defects in the field, the invention provides benzimidazole based on dicarboxylic acid.
Another object of the present invention is to propose a process for the preparation of said benzimidazoles based on dicarboxylic acids.
A third object of the present invention is to propose the use of said benzimidazoles based on dicarboxylic acids.
The fourth purpose of the invention is to provide a photosensitive fluorescence labeling method.
The technical scheme for realizing the aim of the invention is as follows:
a dicarboxylic acid based benzimidazole having the general structural formula:
r is a saturated or unsaturated carbon chain with 2-18 carbon atoms.
A preparation method of benzimidazole based on dicarboxylic acid comprises the steps of carrying out dehydration condensation reaction on o-phenylenediamine (OPD) and dicarboxylic acid, wherein the dicarboxylic acid is saturated or unsaturated dicarboxylic acid with 2-18 carbon atoms; preferably, the carboxylic acid is a saturated dicarboxylic acid having 10 to 18 carbon atoms.
Based on the technical scheme of the invention, the series of benzimidazole derivatives containing the free carboxyl long-chain fatty carboxyl can be prepared by using long-chain dibasic acids such as tridecanedioic acid, tetradecanedioic acid, pentadecanedioic acid, hexadecanedioic acid, heptadecanedioic acid, octadecanedioic acid and the like.
Further, the preparation method comprises the following steps:
1) mixing o-phenylenediamine and dicarboxylic acid, and performing reflux reaction by using 1-6 mol/L HCl solution as a solvent and a catalyst of a reaction system.
2) After the reaction is finished, separating and purifying.
Wherein the mass ratio of the o-phenylenediamine (OPD) to the dicarboxylic acid is 0.1-2.
Wherein the mass-volume ratio of the o-phenylenediamine (OPD) to the HCl solution is 10 g: (100-300) mL.
Preferably, in the step 1), the reflux reaction is carried out for 3-24 hours. When the dicarboxylic acid is an unsaturated dicarboxylic acid, the reflux reaction is carried out under the protection of an inert gas (such as nitrogen or argon).
Wherein the step 2) is as follows: after the reaction is finished, carrying out suction filtration to obtain a solid filter cake, washing the solid filter cake with NaOH solution until the pH of the eluate is 7-8, and finishing washing; filtering to obtain a filter cake, and drying the filter cake.
The application of the benzimidazole based on the dicarboxylic acid is applied to insect expelling, sterilization, preparation of anti-cancer drugs, preparation of high-performance composite materials, metal corrosion prevention and photosensitive fluorescence labeling.
A method of photoluminescing a fluorescent label comprising the acts of:
s1: coupling the activated carboxyl with free amino of lysine in bovine serum albumin to form a bovine serum albumin solution with a fluorescent marker;
s2: dissolving the binary carboxylic acid-based benzimidazole of claim 1 in acetone, adding Dicyclohexylcarbodiimide (DCC) in an equal amount, shaking at room temperature, gradually adding dropwise the solution into the bovine serum albumin solution prepared in step S1, and reacting at 0-5 ℃;
s3: after the reaction is finished, the washing product is concentrated by a centrifugal ultrafiltration membrane and then is freeze-dried to obtain the bovine serum albumin with the fluorescent label.
Preferably, step S2 is: dissolving 2- (1-carboxyl n-decane) benzimidazole in acetone, wherein the mass volume ratio of the 2- (1-carboxyl n-decane) benzimidazole to the acetone is (0.01-0.2) g: 10 mL; adding Dicyclohexylcarbodiimide (DCC) with the same amount of substances, and shaking at room temperature to obtain a labeling solution; and (3) dropwise adding the marking solution into the bovine serum albumin solution according to the volume ratio of the marking solution to the bovine serum albumin solution of 1 (3-6), and reacting for 1-3 hours at 4 ℃.
The beneficial technical effects of the invention are embodied in the following aspects:
the long-chain dibasic acid is an important chemical intermediate, and large-scale industrial production is realized. Polyanhydrides are becoming more and more widely used as downstream derivatives in the medical field. A series of different perfumes can be synthesized by using dibasic acid with more than ten carbons as raw material. Moschus synthesized from thirteen carbon sources can be used as perfume fixative. Pentadecanone, muscone and cyclopentadecanolide can be synthesized from pentadecanoic acid or hexadecanedioic acid. The long-chain dibasic acid has wide application prospect in the field of fine industry such as medical intermediates and the like. The benzimidazole derivative containing the free fatty carboxyl provided by the invention is based on the excellent performance of a benzimidazole parent nucleus and the safety, fat solubility and alkali solubility of long-chain dibasic acid in a living body, and provides wider application for the benzimidazole derivative.
The invention utilizes the 'splicing principle' to prepare the benzimidazole derivative containing the free fatty carboxyl, can be used as a fluorescent probe, can also be used as a novel medicament containing a benzimidazole parent nucleus and (or) an intermediate for downstream development and other fields. In the present invention, 2- (1-carboxy-n-decane) benzimidazole was prepared using dodecanedioic acid. Based on the preparation method provided by the invention, the series of benzimidazole derivatives containing the free carboxyl long-chain fatty carboxyl can also be prepared by using long-chain dibasic acids such as tridecanedioic acid, tetradecanedioic acid, pentadecanedioic acid, hexadecanedioic acid, heptadecanedioic acid, octadecanedioic acid and the like.
Detailed Description
The following examples further illustrate the present invention but are not to be construed as limiting the invention.
Example 1
The preparation method of 2- (1-carboxyl n-decane) benzimidazole is as follows:
10g of o-phenylenediamine (OPD) and 20g of dodecanedioic acid (DC12) were weighed out, and the mixture was refluxed for 12 hours using 200mL of a 3M HCl solution as a reaction solvent.
And after the reaction is finished, carrying out suction filtration to obtain a solid filter cake, washing the solid filter cake with NaOH solution, and finishing washing when the solution is 7-8. Filtering to obtain a filter cake. And drying the filter cake to obtain the 2- (1-carboxyl n-decane) benzimidazole.
The detection data of the obtained product are as follows:1H NMR(500MHz，DMSO-d6)：11.93(s，1H)，7.61(m，2H)，7.31(m，2H)，3.64(s，1H)，2.95(m，2H)，2.18(m，2H)，1.80(d，2H)，1.48(m，2H)，1.28(d，12H)。
proved to be 2- (1-carboxyl n-decane) benzimidazole with the structural formula
Example 2
The preparation method of 2- (1-carboxyl n-dodecane) benzimidazole is as follows:
10g of o-phenylenediamine (OPD) and 20g of tetradecanedioic acid (DC14) were weighed out, and the mixture was refluxed for 14 hours using 200mL of a 3M HCl solution as a reaction solvent.
And after the reaction is finished, carrying out suction filtration to obtain a solid filter cake, washing the solid filter cake with NaOH solution, and finishing washing when the solution is 7-8. Filtering to obtain a filter cake. And drying the filter cake to obtain the 2- (1-carboxyl n-dodecane) benzimidazole.
Example 3
The preparation method of 2- (1-carboxyl n-tetradecane) benzimidazole comprises the following steps:
10g of o-phenylenediamine (OPD) and 20g of hexadecanedioic acid (DC16) were weighed out, and the mixture was refluxed for 14 hours using 200mL of a 3M HCl solution as a reaction solvent.
And after the reaction is finished, carrying out suction filtration to obtain a solid filter cake, washing the solid filter cake with NaOH solution, and finishing washing when the solution is 7-8. Filtering to obtain a filter cake. Drying the filter cake to obtain the 2- (1-carboxyl n-tetradecane) benzimidazole.
Example 4
The preparation method of 2- (1-carboxyl n-hexadecane) benzimidazole comprises the following steps:
10g of o-phenylenediamine (OPD) and 20g of heptadecadicarboxylic acid (DC17) were weighed out, and the mixture was refluxed for 14 hours using 200mL of a 3M HCl solution as a reaction solvent.
And after the reaction is finished, carrying out suction filtration to obtain a solid filter cake, washing the solid filter cake with NaOH solution, and finishing washing when the solution is 7-8. Filtering to obtain a filter cake. And drying the filter cake to obtain the 2- (1-carboxyl n-hexadecane) benzimidazole.
Example 5
The preparation method of 2- (1-carboxyl n-octadecane) benzimidazole is as follows:
10g of o-phenylenediamine (OPD) and 20g of eicosanedioic acid (DC20) were weighed out, and reacted with 200mL of a 3M HCl solution as a reaction solvent under reflux for 15 hours.
And after the reaction is finished, carrying out suction filtration to obtain a solid filter cake, washing the solid filter cake with NaOH solution, and finishing washing when the solution is 7-8. Filtering to obtain a filter cake. Drying the filter cake to obtain the 2- (1-carboxyl n-octadecyl) benzimidazole.
Application examples
Example 1 application of 2- (1-carboxy-n-decane) benzimidazole labeled bovine serum albumin:
the activated carboxyl is coupled with the free amino of lysine in the bovine serum albumin to form a bovine serum albumin solution with a fluorescent marker.
2- (1-carboxy-n-decane) benzimidazole 0.01g dissolved in 1mL of acetone, then adding Dicyclohexylcarbodiimide (DCC) in equal amount, shaking at room temperature for 30min to activate the carboxyl group, then gradually dropping into 4mL of bovine serum albumin solution, and reacting at 4 ℃ for 2 hours.
After the reaction is finished, repeatedly concentrating and washing the product by using a centrifugal ultrafiltration membrane, removing small molecular substances, and freeze-drying to obtain the bovine serum albumin labeled by fluorescence.
The obtained fluorescence labeled bovine serum albumin has fluorescence generation under ultraviolet excitation.
Although the present invention has been described in detail above with reference to a general description, specific embodiments and examples, certain additions and optimizations to the discriminant model of the present method may be made on the basis of the present invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (10)
1. A dicarboxylic acid based benzimidazole having the general structural formula:
r is a saturated or unsaturated carbon chain with 2-18 carbon atoms.
2. A preparation method of benzimidazole based on dicarboxylic acid is characterized in that o-phenylenediamine and dicarboxylic acid are subjected to dehydration condensation reaction; the dicarboxylic acid is a saturated or unsaturated dicarboxylic acid with 2-18 carbon atoms, and preferably a saturated dicarboxylic acid with 10-18 carbon atoms.
3. The method for preparing benzimidazole based on dicarboxylic acid according to claim 1, comprising the steps of:
1) mixing o-phenylenediamine and dicarboxylic acid, and performing reflux reaction by using 1-6 mol/L HCl solution as a solvent and a catalyst of a reaction system;
2) after the reaction is finished, separating and purifying.
4. The method for preparing benzimidazole based on dicarboxylic acid according to claim 1, wherein the mass ratio of the o-phenylenediamine to the dicarboxylic acid is 0.1-2.
5. The method for preparing benzimidazole based on dicarboxylic acid according to claim 1, wherein the mass-to-volume ratio of the o-phenylenediamine to the HCl solution is 10 g:
(100～300)mL。
6. the method for preparing benzimidazole based on dicarboxylic acid according to claim 1, wherein the step 1) comprises a reflux reaction for 3-24 h; and when the dicarboxylic acid is unsaturated dicarboxylic acid, carrying out reflux reaction under the protection of inert gas.
7. The method for preparing benzimidazole based on dicarboxylic acid according to claim 1, wherein the step 2) is: after the reaction is finished, carrying out suction filtration to obtain a solid filter cake, washing the solid filter cake with NaOH solution until the pH of the eluate is 7-8, and finishing washing; filtering to obtain a filter cake, and drying the filter cake.
8. The use of a dicarboxylic acid based benzimidazole according to claim 1, wherein the use is in the preparation of anthelmintic, bactericidal, anticancer drugs, high performance composites, metal corrosion protection, photosensory fluorescence labeling.
9. A photosensitive fluorescence labeling method is characterized by comprising the following operations:
s1: coupling the activated carboxyl with free amino of lysine in bovine serum albumin to form a bovine serum albumin solution with a fluorescent marker;
s2: dissolving the dicarboxylic acid-based benzimidazole of claim 1 in acetone, adding dicyclohexylcarbodiimide in an equal amount, shaking at room temperature, gradually adding dropwise the solution into the bovine serum albumin solution prepared in step S1, and reacting at 0-5 ℃;
s3: after the reaction is finished, the washing product is concentrated by a centrifugal ultrafiltration membrane and then is freeze-dried to obtain the bovine serum albumin with the fluorescent label.
10. The photosensitive fluorescent labeling method of claim 9, wherein step S2 is: dissolving 2- (1-carboxyl n-decane) benzimidazole in acetone, wherein the mass volume ratio of the 2- (1-carboxyl n-decane) benzimidazole to the acetone is (0.01-0.2) g: 10 mL; adding dicyclohexylcarbodiimide with the same amount of substances, and shaking at room temperature to obtain a marking solution; and (3) dropwise adding the marking solution into the bovine serum albumin solution according to the volume ratio of the marking solution to the bovine serum albumin solution of 1 (3-6), and reacting for 1-3 hours at 4 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811480165.8A CN111269185B (en) | 2018-12-05 | 2018-12-05 | Benzimidazole based on dicarboxylic acid and preparation and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811480165.8A CN111269185B (en) | 2018-12-05 | 2018-12-05 | Benzimidazole based on dicarboxylic acid and preparation and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111269185A true CN111269185A (en) | 2020-06-12 |
| CN111269185B CN111269185B (en) | 2021-06-11 |
Family
ID=70995010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811480165.8A Active CN111269185B (en) | 2018-12-05 | 2018-12-05 | Benzimidazole based on dicarboxylic acid and preparation and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111269185B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107118249A (en) * | 2017-05-16 | 2017-09-01 | 沈阳药科大学 | 18 β Enoxolone derivatives and its application |
-
2018
- 2018-12-05 CN CN201811480165.8A patent/CN111269185B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107118249A (en) * | 2017-05-16 | 2017-09-01 | 沈阳药科大学 | 18 β Enoxolone derivatives and its application |
Non-Patent Citations (9)
Also Published As
| Publication number | Publication date |
|---|---|
| CN111269185B (en) | 2021-06-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69818987T2 (en) | COMPOSITION AND METHOD FOR DELAYING THE TRANSPORT BY BIOLOGICAL MEMBRANES | |
| CN102898641A (en) | Single active functional group-containing Y-type polyethylene glycol and preparation method thereof | |
| CN111718395B (en) | Prodrug activating compound, prodrug system, preparation method and application thereof | |
| CN102101847A (en) | Method for preparing N-methyl-N'-(2-chloroethyl)piperazine | |
| CN111269185B (en) | Benzimidazole based on dicarboxylic acid and preparation and application thereof | |
| CN110156659B (en) | Preparation method of polyfluoro-substituted 3-hydroxyl oxindole compound | |
| Sepahvand et al. | The magnetic graphene oxide/NHC catalyzed aerobic direct amidation and cross-dehydrogenative coupling of aldehydes | |
| CN107698697A (en) | A kind of triazole of claw type 1,4 connects cyclodextrin molecular and preparation method and application more | |
| CN111848658A (en) | Mitochondrion-targeted BODIPY compound and preparation method and application of liposome-coated nanoparticles thereof | |
| CN109232559B (en) | Synthesis method of [60] fullerene dihydrocarboline derivative | |
| CN100478333C (en) | Chiral and non-chiral diimidazolinylbenzene compounds and synthesis method | |
| CN108864089B (en) | Indolopyridone drug molecule and preparation method and application thereof | |
| CN111166882A (en) | Phthalocyanine-RGD polypeptide-graphene oxide composite nano material and preparation method and application thereof | |
| Bizzarri et al. | Multicomponent synthesis of diaminopurine and guanine PNA’s analogues active against influenza a virus from prebiotic compounds | |
| CN105463439B (en) | The titanium metal material and its preparation method and application of rhodium complex modification | |
| CN100378073C (en) | Dindoly methylane and preparation process thereof | |
| CN103664875B (en) | Isosorbide-5-Nitrae, the synthetic method of 5,6-tetrahydropyrimidinederivatives derivatives | |
| CN109867709B (en) | Preparation method and application of glycyrrhetinic acid series derivatives (TOGA-X) with anti-tumor effect | |
| CN106883185B (en) | Preparation method of 4-chloro-2-trifluoromethylpyrimidine | |
| CN111138435A (en) | Modified methotrexate and preparation method and application thereof | |
| Patil et al. | A Review: Alternative Methods of Preparing 1, 4-Dihydropyridine Derivatives by Hantzsch Reaction | |
| CN106946920A (en) | A kind of preparation method of 4 amino phenyl boronic acid derivative | |
| CN115160234B (en) | Aryl acetate-containing 1,4, 5-trisubstituted imidazole compound, preparation method and application | |
| Ge et al. | Iron-catalyzed C–O bond functionalization of butyrolactam derivatives with various N-/C-nucleophiles | |
| CN108727360A (en) | A kind of preparation method of 2- pyrrole radicals -1,3- morpholine class compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |