CN1263092A - Carboxylic compound and its preparation method and application - Google Patents

Carboxylic compound and its preparation method and application Download PDF

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CN1263092A
CN1263092A CN 99123076 CN99123076A CN1263092A CN 1263092 A CN1263092 A CN 1263092A CN 99123076 CN99123076 CN 99123076 CN 99123076 A CN99123076 A CN 99123076A CN 1263092 A CN1263092 A CN 1263092A
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compound
carbazole
bromo
acetate
propionic acid
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劳文剑
尤进茂
游静
王国俊
欧庆瑜
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Lanzhou Institute of Chemical Physics LICP of CAS
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Lanzhou Institute of Chemical Physics LICP of CAS
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Abstract

The present invention discloses a carboxylic acid compound, its preparation method and application. Its preparation method includes the following steps: mixing carbazole raw material and potassium hydroxide and bromate according to mole ratio of 1 : 5-12 : 11-1.5, using N,N-dimethyl formamide as solvent, at normal pressure using microwave to heat for 2-15 min.. Said invented compound can be used as derivatization reagent in front of high-performance liquid-phase chromatographic column and capillary electrophoretic column, and can be used for fluorescence detection and UV detection of amino acid, amine and aliphatic alcohol.

Description

Carboxylic acid cpd and its production and use
The present invention relates to a kind of carboxylic acid cpd, and its production and use.Say that more specifically what the present invention relates to is a kind of carbazole-9-carboxylic acid cpd of novelty, and preparation method thereof method and purposes.
Japan's publication (No.91,251,564) has disclosed a kind of preparation 1, the method for 4-dimethyl carbazole-9-acetate.Mixture and the carbazole and the ethyl bromoacetate reaction of sodium hydride and methyl-sulphoxide of this method, the reaction times is tens hours.The people who possesses expertise knows that sodium hydride and methyl-sulphoxide mix, and the danger of blast is arranged.Document (J.org.chem 1959.[24] 324) has been reported a kind of method for preparing carbazole-9-propionic acid.This method is raw material with the carbazole, and the first step is made β-(2-nitrile ethyl) carbazole earlier, and second step was that itrile group is hydrolyzed to carboxyl, needs two-step reaction just can make carbazole-9-propionic acid.This method the first step need be made catalyzer with special quaternary amine, just can react.Second one-step hydrolysis is wanted nitrogen protection, and wants strict controlled temperature, and the reaction times is twenties hours.As seen this method operation steps is many, long reaction time, severe reaction conditions.
The purpose of this invention is to provide a kind of carboxylic acid cpd.
Another object of the present invention provides a kind of preparation method of carboxylic acid cpd.
Another purpose of the present invention provides a kind of purposes of carboxylic acid cpd.
The present invention implements by following measure:
A kind of carbazole of novelty-9-carboxylic acid cpd is found, represents with formula (I) compound:
R wherein 1-5, be selected from Cl, Br, I, CH 3, CH 2, CH 2CH 2The particular compound that the present invention relates to general formula (I) expression has: 1. carbazole-9-(2-ethyl) acetate (R 1-4=H, R 5=-CH (C 2H 5)-): fusing point: 125-126 ℃. infrared spectra (KBr): ν (cm -1): 3050 (m), 2900 (w), 1770 (s), 1650 (m), 1540 (m), 1510 (s), 1400 (m), 1280 (m), 1260 (m), 1210 (w), 760 (s), 730 (m). proton nmr spectra δ (ppm): 0.73 (3H, t, J=7.2Hz (CH 3)), 2.06 (2H, m, (CH 2-)), 5.52 (1H, t, J=7.5Hz, (CH-)), 7.22-8.22 (8H, m, (aromatic ring proton)). mass spectrum m/z (relative intensity): 253 (M +, 28) and .2. 3-chloro-carbazole-9-acetate (R 1,3,4=H, R 2=Cl, R 5=-CH 2-): fusing point: 185-186 ℃. infrared spectra (KBr): ν (cm -1) 3050 (m), 2920 (m), 1730 (s), 1640 (w), 1615 (w), 1495 (s), 1380 (w), 1340 (w), 1290 (m), 1243 (s), 950 (w), 900 (w), 845 (m), 820 (m), 755 (m), 730 (m). proton nmr spectra δ (ppm): 5.22 (2H, s, (CH 2-)), 7.18-8.16 (7H, m, (aromatic ring proton)). mass spectrum m/z (relative intensity): 259 (M +, 43) and .3. 3-bromo-carbazole-9-acetate (R 1,3,4=H, R 2=Br, R 5=-CH 2-): fusing point: 194-196 ℃. infrared spectra (KBr): ν (cm -1) 3050 (m), 2925 (m), 1730 (s), 1645 (w), 1615 (w), 1495 (s), 1470 (s), 1380 (w), 1295 (m), 1265 (s), 920 (w), 900 (m), 810 (s), 805 (s), 760 (m), 750 (m). proton nmr spectra δ (ppm): 5.23 (2H, s, (CH 2-)), 7.20-8.18 (7H, m, (aromatic ring proton)). mass spectrum m/z (relative intensity): 303 (M +, 54) and .4. 3-bromo-carbazole-9-propionic acid (R 1,3,4=H, R 2=Br, R 5=-CH 2CH-): fusing point: 130-132 ℃. infrared spectra (KBr): ν (cm -1) 3050 (m), 2925 (m), 1725 (s), 1640 (w), 1610 (m), 1495 (m), 1470 (s), 1360 (m), 1290 (m), 1260 (m), 940 (m), 900 (m), 810 (s), 805 (s), 750 (s), 730 (s). proton nmr spectra δ (ppm): 2.88 (2H, t, J=7Hz, (CH 2-)), 4.72 (2H, t, J=7.2Hz, (N-CH 2)) 7.18-8.32, (7H, m, (aromatic ring proton)). mass spectrum m/z (relative intensity): 317 (M +, 51) and .5. 3,6-two bromo-carbazole-9-propionic acid (R 1,3=H, R 2,4=Br, R 5=-CH 2CH-): fusing point: 185-187 ℃. infrared spectra (KBr): ν (cm -1) 3050 (m), 2925 (m), 1730 (s), 1605 (w), 1490 (s), 1450 (m), 1370 (m), 1310 (m), 1290 (m), 1260 (m), 940 (m), 880 (m), 815 (s), 750 (w), 730 (w). proton nmr spectra δ (ppm): 2.89 (2H, t, J=7.2Hz, (CH 2-)), 4.72 (2H, t, J=7.2Hz, (N-CH 2)) 7.65-8.37, (6H, m, (aromatic ring proton)). mass spectrum m/z (relative intensity): 381 (M +, 17) and .6. 1,3,6-three bromo-carbazole-9-acetate (R 3=H, R 1,2,4=Br, R 5=-CH 2-): fusing point: 177-178 ℃. infrared spectra (KBr): ν (cm -1) 3050 (m), 2920 (m), 1730 (s), 1 650 (w), 1595 (w), 1490 (m), 1460 (m), 1390 (w), 1310 (m), 1260 (m), 1225 (m), 960 (w), 890 (w), 850 (w), 810 (m), 805 (w), 760 (w), 730 (w). proton nmr spectra δ (ppm): 5.62 (2H, s, (CH 2-)) .7..66-8.43, (5H, m, (aromatic ring proton)). mass spectrum m/z (relative intensity): 459 (M +, 9) and .7. 1,3,6-three bromo-carbazole-9-propionic acid (R 3=H, R 1,2,4=Br, R 5=-CH 2CH-): fusing point: 185-186 ℃. infrared spectra (KBr): ν (cm -1) 3050 (m), 2930 (m), 1735 (s), 1610 (w), 1595 (w), 1490 (m), 1455 (m), 1395 (w), 1305 (m), 1260 (m), 1240 (m), 940 (w), 890 (w), 840 (w), 810 (m), 800 (w), 750 (w), 730 (w). proton nmr spectra δ (ppm): 2.06 (2H, t, J=2.4Hz, (CH 2-)), 4.72 (2H, t, J=6.4Hz, (N-CH 2)) 7.64-8.37, (6H, m, (aromatic ring proton)). mass spectrum m/z (relative intensity): 473 (M +, 5) and .8. 1,4-dimethyl-carbazole-9-propionic acid (R 2,4=H, R 1,3=CH 3, R 5=-CH 2CH-): fusing point: 175-177 ℃. infrared spectra (KBr): ν (cm -1) 3050 (m), 2910 (m), 1723 (s), 1630 (w), 1595 (w), 1530 (m), 1490 (m), 1450 (m), 1380 (w), 1310 (m), 1250 (m), 1160 (m), 960 (w), 940 (w), 820 (m), 760 (m), 740 (m). proton nmr spectra δ (ppm): 2.75-2.95 (8H, m, (CH 2-), (CH 3)), 4.91 (2H, t, J=8.0Hz, (N-CH 2)) 7.07-8.25, (6H, m, (aromatic ring proton)). mass spectrum m/z (relative intensity): 267 (M +, 43).
The preparation method of carboxylic acid cpd of the present invention is characterized in that: the carbazole raw material mixed with potassium hydroxide and bromic acid ester, and with N, dinethylformamide is a solvent, under the normal pressure, takes place with microwave induced reaction, intermediate product only just can obtain final product through single step reaction without separation.Need not use catalyzer, aftertreatment is simple, the productive rate height.
Below, preparation method of the present invention is done more detailed description.
The raw material carbazole is mixed with potassium hydroxide, add N, dinethylformamide, subsequently, the dripping bromine acid esters is put into microwave oven and is heated, after question response is finished, add entry, cooling is filtered then, filtrate transfers to acidity with hydrochloric acid, the precipitation that filtration is separated out is after the vacuum-drying, with the mixed solution recrystallization of chloroform and ethanol mixed solvent or acetonitrile and water.Raw material carbazole and potassium hydroxide, bromic acid ester and N, the proportioning of dinethylformamide (mol ratio) is: 1: 5-12: 1.1-1.5: 8-30.Microwave power is in the 225-525W scope.Be 2-15 minute heat-up time in the microwave oven.Chloroform and alcoholic acid proportioning (volume ratio) are: 70-90: 30-10.The proportioning of acetonitrile and water (volume ratio) is 70-95: 30-5.
Compound of the present invention can be used in high performance liquid chromatography and the capillary electrophoresis, as pre-column derivatization reagent, with fluorescence and ultraviolet detection amino acid, amine and Fatty Alcohol(C12-C14 and C12-C18).
Compare the present invention with prior art substantial advantage is arranged: 1. reaction does not need catalyzer, the reaction conditions gentleness, and intermediate product is without separation, and it is few that behaviour does step.2. speed of response is fast, the productive rate height.3. reaction raw materials is easy to get, and reaction cost is low.
Embodiment 1
Synthesize 1,4-dimethyl-carbazole-9-propionic acid.6.0g (0.03mol) 1,4-dimethyl-carbazole, 12.8g (0.225mol) KOH mix in a round-bottomed flask, add 30 milliliters of N, and dinethylformamide drips bromo-propionic acid ethyl ester 6.7g (0.036mol) then.Reaction vessel is put into microwave oven, under microwave power 450W, heated 7 minutes.Take out reaction vessel, add entry, filter, filtrate uses the hydrochloric acid adjust pH of 6N to 1-2.Sedimentation and filtration, vacuum-drying.Thick product obtains white crystal with the mixed solvent recrystallization of chloroform and ethanol (90: 10).The heavy 6.4g of anhydrous product, productive rate 78.5%.Ultimate analysis C 17H 17NO 2: theoretical value (%): C, 76.38; H, 6.41; N, 5.24.; Measured value: C, 75.75; H, 6.34; N, 5.34.
Embodiment 2
Synthesize 1,3,6-three bromo-carbazole-9-propionic acid.4.0g (0.01mol) 1,3,6-three bromo-carbazoles, 5.7g (0.1mol) KOH mix in a round-bottomed flask, add 20 milliliters of N, and dinethylformamide drips bromo-propionic acid ethyl ester 2.2g (0.013mol) then.Reaction vessel is put into microwave oven, under microwave power 375W, heated 6 minutes.Take out reaction vessel, add entry, filter, filtrate uses the hydrochloric acid adjust pH of 6N to 1-2.Sedimentation and filtration, vacuum-drying.Thick product obtains white crystal with the mixed solvent recrystallization of acetonitrile and water (95: 5).The heavy 4.0g of anhydrous product, productive rate 84%.Ultimate analysis C 15H 10NO 2Br 3: theoretical value (%): C, 39.51; H, 2.21; N, 3.07; Measured value: C, 39.26; H, 2.01; N, 2.83.
Embodiment 3
Synthetic carbazole-9-(2-ethyl) acetate.5.0g (0.03mol) carbazole, 9.7g (0.17mol) KOH are mixed in a round-bottomed flask, add 25 milliliters of N, dinethylformamide drips α-bromo-butyric acid methyl esters 7.1g (0.039mol) then.Under microwave power 450w, heated 8 minutes.All the other operations are with embodiment 1.The heavy 4.2g of anhydrous product, productive rate 56%.Ultimate analysis C 16H 15NO 2: theoretical value (%): C, 75.87; H, 5.97; N, 5.53; Measured value: C, 75.80; H, 5.84; N, 5.50.
Embodiment 4
Synthetic 3-chloro-carbazole-9-acetate.2.4g (0.012mol) 3-chloro-carbazole, 4.8g (0.084mol) KOH are mixed in a round-bottomed flask, add 15 milliliters of N, dinethylformamide, dripping bromine ethyl acetate 2.4g (0.014mol) then.Under microwave power 450w, heated 5 minutes.All the other operations are with embodiment 1.The heavy 2.7g of anhydrous product, productive rate 87%.Ultimate analysis C 16H 10NO 2Cl: theoretical value (%): C, 64.75; H, 3.88; N, 5.39; Measured value: C, 64.66; H, 3.91; N, 5.52.
Embodiment 5
Synthetic 3-bromo-carbazole-9-acetate.4.9g (0.02mol) 3-bromo-carbazole, 5.7g (0.1mol) KOH are mixed in a round-bottomed flask, add 20 milliliters of N, dinethylformamide, dripping bromine ethyl acetate 4.3g (0.026mol) then.Under microwave power 375W, heated 7.5 minutes.All the other operations are with embodiment 1.The heavy 5.2g of anhydrous product, productive rate 85%.Ultimate analysis C 14H 10NO 2Br: theoretical value (%): C, 55.29; H, 3.31; N, 4.61; Measured value: C, 55.24; H, 3.18; N, 4.63.
Embodiment 6
Synthetic 3-bromo-carbazole-9-propionic acid.7.95g (0.025mol) 3-bromo-carbazole, 11.4g (0.2mol) KOH are mixed in a round-bottomed flask, add 30 milliliters of N, dinethylformamide drips β-ethyl bromoacetate 5.97g (0.033mol) then.Under microwave power 375W, heated 9 minutes.All the other operations are with embodiment 1.The heavy 6.4g of anhydrous product, productive rate 80%.Ultimate analysis C 15H 12NO 2Br: theoretical value (%): C, 56.62; H, 3.80; N, 4.40; Measured value: C, 56.35; H, 3.53; N, 4.32.
Embodiment 7
Synthesize 3,6-two bromo-carbazole-9-propionic acid.3.25g (0.01mol) 3,6-two bromo-carbazoles, 5.7g (0.1mol) KOH mix in a round-bottomed flask, add 20 milliliters of N, and dinethylformamide drips bromo-propionic acid ethyl ester 2.35g (0.013mol) then.Under microwave power 450w, heated 6 minutes.All the other operations are with embodiment 2.The heavy 3.1g of anhydrous product, productive rate 83%.Ultimate analysis C 15H 11NO 2Br 2: theoretical value (%): C, 47.78; H, 2.94; N, 3.71; Measured value: C, 47.40; H, 2.58; N, 3.59.
Embodiment 8
Synthesize 1,3,6-three bromo-carbazole-acetate.4.0g (0.01mol) 1,3,6-three bromo-carbazoles, 5.7g (0.1mol) KOH mix in a round-bottomed flask, add 20 milliliters of N, dinethylformamide, dripping bromine ethyl acetate 2.35g (0.013mol) then.Under microwave power 450W, heated 10 minutes.All the other operations are with embodiment 2.The heavy 2.2g of anhydrous product, productive rate 47%.Ultimate analysis C 14H 8NO 2Br 3: theoretical value (%): C, 36.40; H, 1.75; N, 3.03; Measured value: C, 35.96; H, 1.62; N, 2.87.

Claims (11)

1. carboxylic acid cpd is characterized in that representing with formula (I) compound: R wherein 1-5, be selected from Cl, Br, I, CH 3, CH 2, CH 2CH 2
2. as the said compound of claim 1, it is characterized in that compound is carbazole-9-(2-ethyl) acetate.
3. as the said compound of claim 1, it is characterized in that compound is 3-chloro-carbazole-9-acetate.
4. as the said compound of claim 1, it is characterized in that compound is 3-bromo-carbazole-9-acetate.
5. as the said compound of claim 1, it is characterized in that compound is 3-bromo-carbazole-9-propionic acid.
6. as the said compound of claim 1, it is characterized in that compound is 3,6-two bromo-carbazole-9-propionic acid.
7. as the said compound of claim 1, it is characterized in that compound is 1,3,6-three bromo-carbazole-9-acetate.
8. as the said compound of claim 1, it is characterized in that compound is 1,3,6-three bromo-carbazole-9-propionic acid.
9. as the said compound of claim 1, it is characterized in that compound is 1,4-dimethyl-carbazole-9-propionic acid.
10. the method for a preparation formula (I) compound,
Figure A9912307600031
R wherein 1-5, be selected from Cl, Br, I, CH 3, CH 2, CH 2CH 2It is characterized in that the carbazole raw material is mixed with potassium hydroxide, add solvent N, dinethylformamide, dripping bromine acid esters, wherein carbazole raw material and potassium hydroxide, bromic acid ester and N then, the mol ratio of dinethylformamide is: 1: 5-12: 1.1-1.5: 8-30, put into microwave oven and heat, power is controlled at 225-525 watt, synthesis under normal pressure 2-15 minute.
11. a formula (I) carboxylic acid cpd, R wherein 1-5, be selected from Cl, Br, I, CH 3, CH 2, CH 2CH 2, can be used in high performance liquid chromatography and the capillary electrophoresis, as pre-column derivatization reagent, with fluorescence and ultraviolet detection amino acid, amine and Fatty Alcohol(C12-C14 and C12-C18).
CN 99123076 1999-11-17 1999-11-17 Carboxylic compound and its preparation method and application Pending CN1263092A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002265446A (en) * 2001-03-06 2002-09-18 Jsr Corp New carbazole derivative and chemically amplified radiation-sensitive resin composition
CN108409634A (en) * 2018-05-10 2018-08-17 曲阜师范大学 Carbazoles fluorescence amine compound label reagent, synthesis and application

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002265446A (en) * 2001-03-06 2002-09-18 Jsr Corp New carbazole derivative and chemically amplified radiation-sensitive resin composition
CN108409634A (en) * 2018-05-10 2018-08-17 曲阜师范大学 Carbazoles fluorescence amine compound label reagent, synthesis and application
CN108409634B (en) * 2018-05-10 2021-04-27 曲阜师范大学 Carbazole fluorescamine compound labeling reagent, synthesis and application

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