CN100412060C - Prepn of-2-(N-carbazolyl)-ethoxy carbohydrazide - Google Patents
Prepn of-2-(N-carbazolyl)-ethoxy carbohydrazide Download PDFInfo
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- CN100412060C CN100412060C CNB2005100062653A CN200510006265A CN100412060C CN 100412060 C CN100412060 C CN 100412060C CN B2005100062653 A CNB2005100062653 A CN B2005100062653A CN 200510006265 A CN200510006265 A CN 200510006265A CN 100412060 C CN100412060 C CN 100412060C
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Abstract
The present invention relates to a preparation method for 2-(N-carbazolyl)-ethoxy carbohydrazide. Potassium hydroxide is used as catalytic agents, 2-(N-carbazolyl)-ethanol is obtained by the reaction of carbazole and 2-bromoethanol in dimethyl sulfoxide solvent, the 2-(N-carbazolyl)-ethanol reacts with phosgene in a dichloromethane solution, srirring is carried out for 24 hours for reaction, and product 2-(N-carbazolyl)-ethyl chloride formic acid ester is obtained. The reaction product is purified through recrystallization, 2-(N-carbazolyl)-ethyl chloride formic acid ester pure products are obtained, the 2-(N-carbazolyl)-ethyl chloride formic acid ester pure products react with hydrazine hydrate, and goal product 2-(N-carbazolyl)-ethoxy carbohydrazide is obtained. The goal product is purified through recrystallization and can be used for derivatization reaction experiments.
Description
Technical field
The present invention relates to a kind of preparation method of fluorescent reagent, relate in particular to the preparation method of a kind of 2-(N-carbazyl)-oxyethyl group carbohydrazide.
Background technology
Because the special construction character of carbazyl, in existing report, research mainly concentrates on the discussion aspect to its quantum nature.As the transition of π-electronics, solvent property to influence of carbazole derivative photoluminescent property etc.The carbazole derivant structure that had been studied photoluminescent property sees attached list 1.On the other hand, carbazole and complexing of metal ion, also can obtain having the material of special optical and electrical properties with copolymerization such as vinylformic acid.With the simple derivatives of carbazole, as the research of fluorescence derivation reagent report is arranged also as carbazole-N-Acetyl Chloride 98Min. etc.According to existing report, available reagent has following defective: reactive behavior is lower, and the speed of deriving is slower, the derived products instability, fluorescence quantum efficiency is higher, and the component detection sensitivity is little before and after the wash-out, must directly answer chromatographically again through the reduction reaction of 8 hours (90 ℃).
Such as primary amine groups fluorescence derivation reagent derived products is Schiff's base (Schiff base) instability, must just can generate the tertiary amines derived thing that usefulness is analyzed in stable being used to through the reduction reaction of 8 hours (90 ℃), and can not reduce ketose.
Summary of the invention
The object of the present invention is to provide a kind of preparation method who can be used as 2-(N-the carbazyl)-oxyethyl group carbohydrazide of fluorescent derivatizing agent.
For achieving the above object, technical scheme of the present invention is that parent adopts suitable reaction conditions with the carbazole, the synthetic target product that obtains.Because the big π key that exists the N atom to get involved in 2-(N-carbazyl)-oxyethyl group carbohydrazide molecule, the synergistic effect of oxyethyl group carbohydrazide excites and the remarkable red shift of emission wavelength it simultaneously, and the molar absorptivity of molecule increases, water-soluble enhancing.Also, can improve the detection sensitivity of sample significantly because the suitable reactivity and the stability of oxyethyl group carbohydrazide make it be more suitable for being used for the fluoroscopic examination of non-fluorescent samples as fluorescence derivation reagent.
The concrete preparation method of the present invention is:
A) with potassium hydroxide be catalyzer, carbazole and ethylene bromohyrin in dimethyl sulfoxide solvent, react 2-(N-carbazyl)-ethanol; Wherein the mass ratio between carbazole, ethylene bromohyrin and the potassium hydroxide is 2-3: 3-4: 1; Temperature of reaction 80-100 ℃, total reaction time 4-6 hour; Mixture is cooled to room temperature, steams solvent, the resistates washing is dried the back and is heated to the boiling extraction with normal hexane, separates out white solid after the cooling;
B) step a product and phosgene are reacted in dichloromethane solution, wherein the mass ratio of step a product and phosgene is 1-1.5: below 1,0 ℃, and stirring reaction 4 hours; Reacting liquid temperature is risen to room temperature kept 10 hours, reaction finishes, and steams solvent, obtains the white solid sample;
C) step b product and hydrazine hydrate were reacted 25-30 minute under the room temperature condition of normal pressure, wherein step b product and hydrazine hydrate mass ratio are 1: 10-12; Unreacted hydrazine and solvent in the reaction solution are removed in evaporation, get target product 2-(N-carbazyl)-oxyethyl group carbohydrazide.
Described preparation method, the product of step a carries out step b again behind the normal hexane recrystallization purifying.
Described preparation method, the product of step b carries out step c again behind the mixed solvent recrystallization purifying of ether and methylene dichloride, and wherein the mixed solvent of ether and methylene dichloride is 3: 1 by volume.
Described preparation method, the product of step c ethyl alcohol recrystallization purifying.
The present invention promptly can be used for the derivative reaction experiment through the target product of above-mentioned steps preparation through recrystallization purifying.
The fluorescent reagent fluorescence intensity of the present invention's preparation is bigger, and reagent react is active high, and derivatize speed is fast, and derived products is stable, the fluorescence quantum efficiency height.
Preparation condition of the present invention requires not harsh.Owing to excite the remarkable red shift with emission wavelength, the background interference that solvent composition causes in the testing process reduced.The component detection sensitivity is little before and after the wash-out, and product can be used for stratographic analysis at once, and need not further reduce
Preparation of the present invention and fluorescent reagent can be used as fluorescence, the ultraviolet derivative reagent is used for stratographic analysis, can improve detection sensitivity greatly and separate with improving, and have a good application prospect.
Description of drawings
Fig. 1 is that 2-of the present invention (N-carbazyl)-oxyethyl group carbohydrazide carries out column front derivation fluoroscopic examination color atlas to 5 kinds of sugar.
Fig. 2 is that 2-of the present invention (N-carbazyl)-oxyethyl group carbohydrazide carries out column front derivation ultraviolet detection color atlas to 5 kinds of sugar.
Peak value sequence number among above-mentioned Fig. 1 and Fig. 2 is represented respectively: 1-lactose (lactose), 2-seminose (mannose), 3-glucose (glucose), 4-rhamnosyl (rhamnose), 5-sorbose (sorbose).
Embodiment
In the round-bottomed flask of 500ml, add carbazole 30g, methyl-sulphoxide 150mL, start induction stirring and heating, in 20 minutes, 10g potassium hydroxide is added in batches, solution temperature keeps 100 ℃ of following reflux to stir 30 minutes, the ethylene bromohyrin of 40g was added in 1 hour, and temperature continues to keep 100 ℃ to continue the reflux stirring reaction 2.5 hours down, and solution changes dun gradually into.Mixture in the flask is cooled to room temperature, after reaction finishes, solvent is steamed under the condition of oil bath heating with Rotary Evaporators, the resistates water is given a baby a bath on the third day after its birth inferior, dry the back and be heated to the boiling extraction with normal hexane, separate out white solid after the cooling, filter cake is used normal hexane recrystallization twice again behind the suction filtration, gets white needle-like crystals.
The 15g phosgene is dissolved in the 100ml methylene dichloride, pour in the three-necked flask of 500ml, under the condition of induction stirring and cryosel bath, 22.5g 2-(N-carbazyl)-ethyl chloroformate is dissolved in the methylene dichloride of 40ml and kept 0 ℃ of following induction stirring 4 hours, slowly reacting liquid temperature being risen to room temperature kept 10 hours, reaction finishes and with Rotary Evaporators solvent is steamed, and obtains the white solid sample.Press the mixed solvent recrystallization of (3: 1) with ether and methylene dichloride again, product is a white needle-like crystals.
About 1g 2-(N-carbazyl)-ethyl chloroformate is dissolved in the 30mL acetonitrile, under quick agitation condition, above-mentioned solution slowly is added drop-wise in the 10g hydrazine hydrate, behind the question response 30 minutes, reaction solution is removed unreacted hydrazine and solvent being lower than under 40 ℃ of conditions rotary evaporation in vacuo, get the white solid thing, can pass through ethyl alcohol recrystallization, get white needle-like crystals.
Reagent operational condition and effect:
Carbazole-9-oxyethyl group carbohydrazide solution: accurately take by weighing 32mg carbazole-9-oxyethyl group carbohydrazide and add in the 10mL volumetric flask, be diluted to scale with anhydrous acetonitrile, concentration is 1.2 * 10
-2Mol/L; Neutral sugar solution: accurately take by weighing each 10mg of a certain amount of 5 kinds of neutral sugars (lactose, seminose, glucose, rhamnosyl, sorbose) and insert in the 10mL volumetric flask, be diluted with water to scale, total concn is 10g/L.
Get 100 μ L neutral sugar standard substance mixed solutions, add isopyknic carbazole-9-oxyethyl group carbohydrazide solution, add 10 μ L Glacial acetic acid then, behind 65 ℃ of heating in water bath for reaction 5h, be cooled to room temperature, get 10 μ L and be diluted to 200 μ L, sample introduction 5 μ L.Experimentize by following chromatographic separation condition, the results are shown in Figure 1, Fig. 2.
Chromatographic separation condition:
Mobile phase A: ammonium acetate buffer solution (50mmol/L, pH=5), Mobile phase B: acetonitrile; Gradient condition: 0min=70%A, 10min=70%A, 11min=0%A, 30min=0%A; Flow velocity: 1mL/min; Column temperature: room temperature; The fluorescence excitation of derivative and emission wavelength are λ ex/ λ em=293/360nm; Ultraviolet detection wavelength: 254nm.Hypersil ODS2 chromatographic column (150 * 4.6mm, i.d, Dalian Yi Lite scientific instrument company limited).
Subordinate list 1: " carbazole " derivant structure of bibliographical information:
| Carbazole derivates | Document |
| (Carbazole)-(CH2)n-(Terephthalic Acid Methyl Ester) | J.Phys.Chem.1996，100：5019295-19302. |
| 11-(9-carbazole)urdecanoic acid | J.Phys.Chem.B 1999，103：408514-8523. |
| 2-hydroxy-1-carbazole carboxylate | Publication date 22 Jun 1993 Analytical Abstracts |
| 3-methacrylamide-9-carbazole | Publication date 2000 Plastics Rubber Fibers |
| 5H-benzo[b]carbazole | Publication date 15 Dec 1988 Analytical Abstracts Publication date Sep 1992 Analytical Abstracts |
| 7H-dibenzo[c，g]carbazole | Chem Biol Interact 1994 Nov，93：2：139-53 Carcinogenesis 1989 Dec，10：12：2187-95 Carcinogenesis 1989 Mar，10：3：419-27 Chem Res Toxicol 1993 May-Jun，6：3：345-50 Chem Res Toxicol 1992 Jan-Feb，5：1：130-3 |
| 9-(4-cyanophenyl)-carbazole Abstracts | Publication date 1999 Beilstein |
| carbazole acetic acid derivative | J Chromatogr 1991 Jun 14，567：1：175-83 Publication date 14Jun 1991 Analytical Abstracts |
| carbazole alkaloid derivatives | Publication date Feb 1995 Analytical Abstracts |
| carbazole derivatives | Can.J.Chem.1989，67：2142-2147. |
| carbazole derivatives in cationic polymerization | Publication date 2000 Plastics Rubber Fibers |
| carbazole*B complexes(B＝H2O， D2O，NH3) | J.Chem.Phys.1986，85：31234-1246. |
| carbazole-9-acetylbenzenedisulfonate | Publication date Jun 1999 Analytical Abstracts |
| carbazole-9-N-(2-methyl)-acetyl-benze ne-disulfonate | Publication date Nov 1999 Analytical Abstracts |
| carbazole-9-propionyl chloride | Analytica Chimica Acta 1998，367：1-3：81-91 |
| carbazole-9-yl-acetyl chloride | Analytica Chimica Acta 1999，382：l-2：5l-65 |
| carbazole-9-ylpropionic acid | Publication date Mar 1999 Analytical Abstracts |
| carbazole-labeled phospholipid | Chem Biol Interact 1980 Jur，30：3：309-23 Chem Phys Lipids 1980 Jan，26：1：1-40 |
| carbazole-N-(2-methyl)acetyl chloride | Publiation date 2 Jul 1999 Analytical Abstracts |
| carbazole-ruthenium complexes | Inorganica Chimica Acta 1999，288：2：134-141 |
| Carbazole-Viologen Linked Compounds | Tetrahedron Lett.1998，39：386915-6918 |
| methylene-linked carbazole | Chem.Phys.Lett.1999，307：1-28-14. |
| N-(2-chloroethyl)carbazole | J.Phys.Chem.1981，85：142047-2050 |
| N-(2-cyanoethyl)carbazole | J.Phys.Chem.1981，85：142047-2050 |
| N-(2-iodoethyl)carbazole | J.Phys.Chem.1981，85：142047-2050 |
| N-(2-Naphthylmethyl)carbazole | Bull.Chem.Soc.Jpn.1996，69：71849-1854. |
| N-(4-Cyanophenyl)carbazole | J.Chem.Soc.Faraday Trans.1992，88：192799-2804 |
| N-(9-anthryl)carbazole | J.Phys.Chem.1996，100：4718392-18398. |
| N-Methyl Carbazole | Russ.J.Phys.Chem.(Engl.Transl.)1997，71：7 1177-1178. |
| N-vinyl carbazole | Publication date 1997 Plastics Rubber Fibers |
| Oligomers and polymers of carbazole | Publication date 1995 Chemical Engineering and Biotechnology Abstracts |
| peptidyl-3-amino-9-ethyl-carbazole | EMBO J 1982，1：3：303-6 |
| poly[N-(2′-ethylhexyl)-carbazole-3，6-d iyl-1，3，4-oxadiazole-2，5-diyl](PCO) | Synthetic Metals 1999，100：3：297-301 |
| pyrazidole [2，3，3a，4，5，6-hexahydro-8-methyl-1H- pyrazino[3，2，1-jk]carbazole hydrochloride] | Publication date Jan-Feb 1988 Analytical Abstracts |
| tetrahydrocarbazole | Anal Chem 1976 Jan，48：1：144-55 |
Claims (4)
1. the preparation method of a 2-(N-carbazyl)-oxyethyl group carbohydrazide, its key step is:
A) with potassium hydroxide be catalyzer, carbazole and ethylene bromohyrin in dimethyl sulfoxide solvent, react 2-(N-carbazyl)-ethanol; Wherein the mass ratio between carbazole, ethylene bromohyrin and the potassium hydroxide is 2-3: 3-4: 1; Temperature of reaction 80-100 ℃, total reaction time 4-6 hour; Mixture is cooled to room temperature, steams solvent, the resistates washing is dried the back and is heated to the boiling extraction with normal hexane, separates out white solid after the cooling;
B) step a product and phosgene are reacted in dichloromethane solution, wherein the mass ratio of step a product and phosgene is 1-1.5: below 1,0 ℃, and stirring reaction 4 hours; Reacting liquid temperature is risen to room temperature kept 10 hours, reaction finishes, and steams solvent, obtains the white solid sample;
C) step b product and hydrazine hydrate were reacted 25-30 minute under the room temperature condition of normal pressure, wherein step b product and hydrazine hydrate mass ratio are 1: 10-12; Unreacted hydrazine and solvent in the reaction solution are removed in evaporation, get target product 2-(N-carbazyl)-oxyethyl group carbohydrazide.
2. by the preparation method of claim 1, it is characterized in that the product of step a carries out step b again behind the normal hexane recrystallization purifying.
3. by the preparation method of claim 1, it is characterized in that the product of step b carries out step c again behind the mixed solvent recrystallization purifying of ether and methylene dichloride, wherein the mixed solvent of ether and methylene dichloride is 3: 1 by volume.
4. by the preparation method of claim 1, it is characterized in that the product of step c ethyl alcohol recrystallization purifying.
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| CNB2005100062653A CN100412060C (en) | 2005-01-27 | 2005-01-27 | Prepn of-2-(N-carbazolyl)-ethoxy carbohydrazide |
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| CNB2005100062653A CN100412060C (en) | 2005-01-27 | 2005-01-27 | Prepn of-2-(N-carbazolyl)-ethoxy carbohydrazide |
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| CN100412060C true CN100412060C (en) | 2008-08-20 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5079260A (en) * | 1989-06-22 | 1992-01-07 | Nova Pharmaceutical Corporation | Method for treating inflammation and compounds and compositions suitable for use therein |
| US5101059A (en) * | 1989-12-05 | 1992-03-31 | Research Corporation Technologies, Inc. | Amino acid protecting groups |
| CN1415605A (en) * | 2002-11-29 | 2003-05-07 | 南京大学 | Method for preparing N-ethyl carbazole |
-
2005
- 2005-01-27 CN CNB2005100062653A patent/CN100412060C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5079260A (en) * | 1989-06-22 | 1992-01-07 | Nova Pharmaceutical Corporation | Method for treating inflammation and compounds and compositions suitable for use therein |
| US5101059A (en) * | 1989-12-05 | 1992-03-31 | Research Corporation Technologies, Inc. | Amino acid protecting groups |
| CN1415605A (en) * | 2002-11-29 | 2003-05-07 | 南京大学 | Method for preparing N-ethyl carbazole |
Non-Patent Citations (4)
| Title |
|---|
| synthesis and application of fmoc-hydrazine for thequantitative determination of saccharides by reversed-phasehigh-performance liquid chromatography in the low andsubpicomole range. Ren-En Zhang, et al.analytical biochemistry,Vol.195 . 1991 * |
| 咔唑－9－乙基氯甲酸酯柱前衍生氨基酸胶束电动色谱分离. 张琳，尤进茂等.色谱，第22卷第2期. 2004 * |
| 昨唑-9-乙氧基碳酰肼柱前衍生中性糖的高效液相色谱分析. 张琳，张曦等.分析化学，第32卷第8期. 2004 * |
| 痕量氨基糖和中性单糖的高效毛细管电泳及液相色谱分析. 林启山等.色谱，第13卷第1期. 1995 * |
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