CN1214337A - Ultramicro test method for condensed aromatic ring substituted acyl chlorides and its derivative - Google Patents
Ultramicro test method for condensed aromatic ring substituted acyl chlorides and its derivative Download PDFInfo
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- CN1214337A CN1214337A CN 97119148 CN97119148A CN1214337A CN 1214337 A CN1214337 A CN 1214337A CN 97119148 CN97119148 CN 97119148 CN 97119148 A CN97119148 A CN 97119148A CN 1214337 A CN1214337 A CN 1214337A
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Abstract
The condensed aromatic ring substituted acyl chloride is excellent UV and fluorescent probe for HPLC pre-column and post-column derivating ultramicro separation and detection for hydroxyl containing matters, and it has important application value in chemical, medicine, material, environment and life sciences.
Description
The present invention relates to the synthetic and derivatize ultramicro test method that thick aromatic ring replaces the acyl chloride compound.
The medicine of many efficient hydroxyls such as choline medicine, hormone, toxin and anticarcinogen etc. are because consumption is very few, Plasma Concentration is lower after causing the distribution general metabolism, and they often do not contain the intensive luminophore again, therefore can not detect with common opticinstrument method in pharmacokinetics and clinical study.Overcoming the effective means of this difficulty is that medicine is carried out chemical derivatization, promptly by chemical reaction simply fast, fluorescence chromophoric group in the connection (being fluorescent probe), thus available luminoscope detection by quantitative it.This method than optoacoustic, electricity lead, quantitative detecting method sensitivity such as refractive power, IR and NMR will greatly improve, can avoid simultaneously problems such as radiocontamination in the Radiolabelling method, labeling effciency are lower again, in detecting, medicine poisonous substance ultramicron has important value, and very wide in Application for Field prospects such as fine chemistry industry, environmental engineering and medical and health.
Ultraviolet or fluorescent probe technique are a kind of optical physics and photochemical characteristics of utilizing probe compound, physics and chemical process, the structure that detects certain exotic materials and the physical properties of some system of research and the method for quantitative analysis allied compound on molecular level, its basic characteristics are the dynamic time responding ranges with high sensitivity and broad.The synthetic effective derivatization reagent of design is one of committed step in fluorescence derivation-instrument detecting method.A good derivatization reagent must have reaction active groups and the big detection of active group of instrument detecting response that reacts rapidly with medicine simultaneously.Fluorescence detection method is very extensive at trace or ultramicron application in pharmaceutical analysis.Therefore design is synthesized ultraviolet or fluorescent detection probe compound and is carried out applied research, will improve the sensitivity of analyzing and testing greatly, thereby promote relevant therewith pharmaceutical chemistry, analytical chemistry and organic chemistry, biological chemistry and environment and the development of Materials science, and will play a significant role in fields such as medical and health, fine chemistry industry and national defence.Very active at this area research both at home and abroad, the ultraviolet or the fluorescent probe of compounds such as detection amino are a lot of, use also more extensive.But the research of the ultraviolet of oxy-compound or fluorescent probe is less relatively, and derivative reaction is subject to disturb, so this respect makes little progress, and waits further reinforcement.
The objective of the invention is design and synthesized a series of thick aromatic rings replacement acyl chloride compounds and derivative thereof, and it is used as the ultraviolet or the fluorescent probe of derivatize oxy-compound, can ultramicron detect hydroxyl medicine and steroid hormone and T-2 toxin etc., improve 1～3 more than the order of magnitude than usual method, be in international most advanced level.
According to the quantum optics theory, fluorescence is the radiation of molecular excitation singlet degradation to the generation of ground state singlet, is everlasting 10
-9Finish in second, because the special conjugated structure system of aromatic condensed ring, make excited state be difficult for releasing energy by modes such as vibrations, and easily emitting fluorescence is got back to ground state, and conjugated system is bigger, the fluorescent quantum emission probability height of may healing, this has just determined condensed ring fragrance to replace the special significance of acyl chloride compound aspect the derivatize fluoroscopic examination.This class acyl chloride fluorescent probe can be quickly and alcohol compound generation derivative reaction, has very high detection sensitivity, be used widely in researchs such as the ultramicro-analysis of contraceptive steroid, atropic category anticholinergic drug etc. and T-2 toxin dynamic metabolism, detectability is expected to reach fmol or Fg level level.The present invention designs the derivative reaction that the branched probe of synthetic is particularly suitable for high steric hindrance oxy-compound.
The derivative reaction of high steric hindrance oxy-compound
The thick aromatic aldehyde of synthetic important intermediate of the present invention can fine derivatize ultramicron detect hydrazine class rocket propellant, hydrazine class medicine and other hydrazine class compound, detectability can reach fmol or fg level level, improves 3 more than the order of magnitude than common chemical method, vapor-phase chromatography.
The derivative reaction of rocket propellant unsymmetrical dimethyl hydrazine
Be the synthesis route of the present invention 9-anthracene acrylate chloride, 9-anthracene propionyl chloride and the 1-pyrene acrylate chloride designed and Implemented below.Many steps can be improved with physical techniques such as ultrasonic wave, infrared, microwave catalysis or its reasonable combination method.
The route of synthesis of 9-anthracene acrylate chloride
The route of synthesis of 9-anthracene propionyl chloride
The route of synthesis of Fig. 1-pyrene acrylate chloride
Above-mentioned 9-anthracene propionic acid can prepare with 9-anthracene vinylformic acid catalytic hydrogenation.
The present invention has also prepared various thick aromatic rings with similar method and has replaced acyl chlorides.The present invention adopts ultrasonic wave, infrared and physical technique and the above-mentioned relevant synthetic chemistry reactions steps of reasonable combination method catalysis thereof such as microwave, has shortened the reaction times than usual method, has improved reaction yield; Ultramicron detects oxy-compound, and detectability improves 1～3 more than the order of magnitude than usual method.
Be that example is specifically set forth the present invention with the synthetic etc. of 9-anthracene propionyl chloride, 9-anthracene propionyl chloride and 1-pyrene acrylate chloride below, but the compound that the present invention relates to is not limited to this.
Synthesizing of embodiment one 9-anthracene acrylate chloride
The 9-anthraldehyde that in the 250mL round-bottomed flask, adds 2.06g (0.01mol), 1.41g (0.013mol) propanedioic acid, 3mL pyridine and 0.5mL piperidines, induction stirring backflow 4h (about 80 ℃ of oil bath temperatures).Continue after reaction is finished to stir to be cooled to room temperature, add 20mL distilled water, add dilute hydrochloric acid and make solution be acid; To put into another round-bottomed flask behind the solid drying of separating out, heat 15min in temperature is 120 ℃ oil bath, be warming up to 180～190 ℃ of decarboxylation 1h then or use microwave reaction 8min, solid begins dissolving at 138 ℃, and liquid is black.Be cooled to room temperature, liquid becomes the dark red dope.Glacial acetic acid with 12mL chlorinated benzene and 0.5mL carries out recrystallization, drying; Use 8mL chlorinated benzene and 0.3mL glacial acetic acid recrystallization again, drying is used the methyl aceto acetate recrystallization at last, yellow needle-like crystal 9-anthracene vinylformic acid, output 2.01g, productive rate 81.0%, mp.247～248 ℃.Ultimate analysis C
17H
12O
2(M=248.3), calculated value (%): C82.24, H4.87; Experimental value (%): C82.09, H4.57.IR (cm
-1): 1695 (C=O), 1643 (C=C) .MS (m/z): 248 (M
+), 231 (M
+-OH), 203 (M
+-CO
2H), 176 (M
+-CH=CHCO
2H-1), 101 (C
8H
5), 75 (C
6H
3), 44 (CO
2).
9-is feared vinylformic acid 1.24g (0.005mol) and thionyl chloride 2ml, anhydrous chloroform 4ml mixes, stirring and refluxing 1h in the oil bath, steam and remove low-boiling-point substance, use normal heptane: mixed solvent dissolved solids, the suction filtration of anhydrous chloroform=1: 4, repeat this operation for several times, yellow needle-like crystal 1.04g, productive rate 77.6%, mp.119～121 ℃. ultimate analysis C
17H
11OCl (M=266.73), calculated value (%): C76.55, H4.16. experimental value (%): C76.65, H4.29.IR (liquid-film method) cm
-1: 1690 (C=O), 1630 (C=C) .MS (m/z): 266 (M
+), 231 (M
+-Cl), 202 (M
+-COCl-1), 176 (M
+-CH=CHCOCl), 150 (C
12H
6), 116 (C
9H
8), 101 (C
8H
5), 88 (CH ≡ CCOCl), 75 (C
6H
3).
1H NMR (CDCl
3), δ (ppm): 6.73 (1H, d), 7.5-7.6 (4H, m), 8.05 (2H, d), 8.22 (2H, d), 8.54 (1H, s), 8.9 (1H, d).
13C NMR (CDCl
3), δ (ppm): 148 (COCl), 124-131.5 (C-14), 77 (C-2).
Synthesizing of embodiment two 9-anthracene propionyl chlorides
With 1.22g (0.02mol) potassium hydroxide, 22mL dehydrated alcohol, 0.14g Tetrabutyl amonium bromide place three mouthfuls of round-bottomed flasks of 100mL, stir and add 2.78g (0.014mol) 9-anthrone down, add 1.05mL (0.015mol) vinyl cyanide under the room temperature, drip in the process control reaction system warm below 45 ℃.Dropwise post-heating backflow 2h, in treating below the temperature drop to 50 ℃ after, it be acid dripping 1: 1 hydrochloric acid soln to reaction solution, adds water 4mL, normal pressure steams except that most of organic solvent down, brown oil occurs, cools off hypsokinesis and goes out aqueous acid.Add the 15mL concentrated hydrochloric acid, stirring and refluxing 3h or ultrasonic wave catalysis 0.5h, cooled and filtered is washed 3 times, gets brown solid 9-anthrone-10-propionic acid with the glacial acetic acid recrystallization, output 2.31g, productive rate 60.4%, mp.253～255 ℃. ultimate analysis C
17H
14O
3(M=266.3), calculated value (%): C76.42, H5.40.
Get 2.66g (0.01mol) 9-anthrone-10-propionic acid and place there-necked flask, add the 68mL strong aqua, stir gradation adding 12.6g zinc powder down, and in oil bath, react 5h (bathing 90～95 ℃ of temperature).Be yellow liquid after reaction is finished, lower floor is the gray solid precipitation, filters, and washes zinc powder 1 time with 1: 1 weak ammonia.Merge washings and filtrate, add hydrochloric acid soln (1: 1) under stirring, get yellow cotton-shaped solid to acid.Solid collected by filtration is washed 3 times, and oven dry back adds an amount of glacial acetic acid, heated and boiled 5～10min, cooled and filtered, with glacial acetic acid washing 1 time, dry faint yellow solid.Use the methyl aceto acetate recrystallization, faint yellow needle-like crystal, output 2.15g, productive rate 86.0%, mp186～187 ℃.Ultimate analysis C
17H
14O
3(M=250.3), calculated value (%): C81.58, H5.64; Experimental value (%): C81.90, H5.32.
1H NMR (CDCl
3), δ (ppm): 2.9 (2H, t), 4.05 (2H, t), 7.55 (4H, m), 8.08 (2H, d), 8.30 (3H, d).
The experimental implementation of preparation 9-anthracene propionyl chloride is similar with the above-mentioned method for preparing 9-anthracene acrylate chloride, and the raw material consumption is 9-anthracene propionic acid 12.5g (0.005mol), thionyl chloride 2ml, and anhydrous chloroform 4ml. is last must product crystal 1.056g, productive rate 78.6%. ultimate analysis C
17H
13OCl (M=268.79), calculated value (%): C75.97, H4.87. experimental value (%): C75.91, H4.90.MS (m/z): 268 (M
+), 33 (M-Cl), 204 (M-COCl), 203 (C
16H
11), 191 (C
15H
11), 189 (C
15H
9).
Synthesizing of embodiment three 1-pyrene acrylate chlorides
The acrylic acid preparation of 1-pyrene
With 1-pyrene formaldehyde 2.30g (0.01mol), propanedioic acid 1.41g (0.013mol), pyridine 6ml and piperidinyl-1 ml add in the round-bottomed flask of 250ml successively, stirring and refluxing 4h or microwave catalysis 8min in the oil bath.After the cooling, add 5mol/L
-1Hydrochloric acid soln, filter, drying solid.Be placed on again in the oil bath, be warming up to 180-190 ℃ of 1h,, use 70ml methyl aceto acetate recrystallization again with 100ml chlorinated benzene and 5ml glacial acetic acid recrystallization, yellow needle-like crystal 1g, productive rate 36.8%, mp.279～281 ℃, ultimate analysis C
19H
12O
2(M=272.20), calculated value (%): C83.84, H4.44. experimental value (%): C84.11, H4.23.IR (liquid-film method) cm
-1: 1690 (C=O), 1640 (C=C) .MS (m/z): 273 (M
++ 1), 272 (M
+), 228 (M
+-COOH), 200 (M-CH=CHCOOH), 136 (C
11H
4), 113 (C
9H
5), 100 (C
18H
4), 44 (CO
2).
Synthesizing of 1-pyrene acrylate chloride
Experimental implementation is synthetic with above-mentioned 9-anthracene acrylate chloride, and the raw material consumption is 1-pyrene vinylformic acid 1.36g (0.005mol), thionyl chloride 2ml, anhydrous chloroform 5ml.Get product crystal 1.03g, productive rate 71.2%.Ultimate analysis C
19H
11OCl (M=290.79), calculated value (%): C78.48, H3.81. experimental value (%): C78.40, H3.74.FAB-MS (m/z): 292 (M
++ 1), 56 (M-Cl), 228 (M-COCl), 200 (M-CH=CHCOCl).
Embodiment four ultramicron detect
The present invention's usefulness 9-anthracene acrylate chlorides etc. are as HPLC pre-column derivatization reagent, and ultramicron ultraviolet detection anticholinergic agents and steroid hormone and T-2 toxin etc. have obtained satisfied result.Partial results is seen attached list.If further optimal conditions, minimum detectability can reach fg level level.
The HPLC characteristic of subordinate list 9-anthracene acrylate chloride derivatize oxy-compound
| Compound | The hydroxyl classification | Moving phase acetonitrile: water | Retention time R t(min) | Detectability *(pmol) |
| Coromegine Scopolamine testosterone T-2 toxin | One-level hydroxyl one-level hydroxyl two basic hydroxyl two basic hydroxyls | ????65∶35 ????65∶35 ????75∶25 ????70∶30 | ????30.08 ????19.24 ????22.60 ????16.78 | ????0.02 ????0.05 ????0.001 ????0.05 |
*Detect in the UV380nm place.
Claims (6)
1. thick aromatic ring replaces acyl chloride compound and derivative and their synthesis route and improves one's methods.
2. according to claim 1, the general structure that wherein said thick aromatic ring replaces acyl chloride compound and derivative thereof is R-Ar-(X)
nCOCl
R=H, halogen contains the alkyl or the alkoxyl group of 1～18 carbon atom; X=CH
2, CH=CH;
N=0,1,2,3,18 (except the 9-anthracene acyl chlorides of n=0)
3. institute's synthetic compound comprises before the HPLC post or post-column derivatization at the derivatize oxy-compound in the claim 1, and separation, ultraviolet or fluorescent quantitation detect in as the application of ultraviolet probe or fluorescent probe.
4. the ultraviolet of the claim 1 thick aromatic aldehyde derivatize of a synthetic important intermediate hydrazine class compound or the method for fluoroscopic examination.
5. according to claim 4, wherein said thick aromatic aldehyde chemical structure of general formula is:
R-Ar-CHO
R=H, halogen contains the alkyl of 1～18 carbon atom, alkoxyl group and aryl; Ar explains as claim 2.
6. according to claim 1, wherein said improving one's methods is meant method with physical technique such as ultrasonic wave, infrared and microwave and the relevant reaction of reasonable combination catalysis thereof, raising reaction efficiency.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97119148A CN1075491C (en) | 1997-10-15 | 1997-10-15 | Ultramicro test method for condensed aromatic ring substituted acyl chlorides and its derivative |
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|---|---|---|---|
| CN97119148A CN1075491C (en) | 1997-10-15 | 1997-10-15 | Ultramicro test method for condensed aromatic ring substituted acyl chlorides and its derivative |
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|---|---|
| CN1214337A true CN1214337A (en) | 1999-04-21 |
| CN1075491C CN1075491C (en) | 2001-11-28 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106946677A (en) * | 2017-04-20 | 2017-07-14 | 深圳市华星光电技术有限公司 | Fused ring compound and its application, electroluminescent device and preparation method thereof |
-
1997
- 1997-10-15 CN CN97119148A patent/CN1075491C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106946677A (en) * | 2017-04-20 | 2017-07-14 | 深圳市华星光电技术有限公司 | Fused ring compound and its application, electroluminescent device and preparation method thereof |
| CN106946677B (en) * | 2017-04-20 | 2019-07-12 | 深圳市华星光电半导体显示技术有限公司 | Fused ring compound and its application, electroluminescent device and preparation method thereof |
| US10424738B2 (en) | 2017-04-20 | 2019-09-24 | Shenzhen China Star Optoelectronics Semiconductor Display Technology Co., Ltd | Condensed-cyclic compound, electroluminescent device and method for manufacturing thereof |
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