NL2034563A - Indole compound, its preparation method and application in detection of aldehydes and ketones - Google Patents

Indole compound, its preparation method and application in detection of aldehydes and ketones Download PDF

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NL2034563A
NL2034563A NL2034563A NL2034563A NL2034563A NL 2034563 A NL2034563 A NL 2034563A NL 2034563 A NL2034563 A NL 2034563A NL 2034563 A NL2034563 A NL 2034563A NL 2034563 A NL2034563 A NL 2034563A
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ketones
aldehydes
indole
detection
compound
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Cao Ying
Wang Sufang
Feng Xueliang
Dong Huaijin
Li Mingxiao
Meng Tian
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Chinese Res Acad Env Sciences
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
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    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
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Abstract

The present invention discloses a new indole compound, which is used as a derivatization reagent in the detection of aldehydes and ketones in water environment by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS). The reaction of the new indole compound with aldehydes and ketones has simple reaction conditions, and the product has sensitive mass spectrum response. The detection method has the advantages of mall matrix interference, low detection limit, short analysis time, and accurate quantification. The present invention also discloses a preparation method of the indole compound, which adopts known and available raw materials, and multi-step reaction to successfully synthesize a new compound that can be used for the the detection of aldehydes and ketones in water by UHPLC-MS/MS.

Description

INDOLE COMPOUND, ITS PREPARATION METHOD AND APPLICATION IN
DETECTION OF ALDEHYDES AND KETONES
TECHNICAL FIELD
The present invention relates to the field of aldehvde and ketone detection, and in particular to an indole compound, its preparation method and application in detection of aldehydes and ketones.
BACKGROUND
Aldehydes and ketones have severe irritation to human eyes, skin and respiratory mucosa, and partial aldehydes and ketones can induce carcinogenesis in animals. Detection mehod of aldehydes and ketones generally includes spectrophotometric methods, liquid chromatography methods, liquid chromatography-mass spectrometry methods, gas chromatography methods, etc. Currently, 2 4-dinitrophenyl hydrazine (DNPH) is generally used to react with aldehvdes and ketones to obtain hydrazone compounds, which are separated by liquid chromatography or gas chromatography, and then detected by ultraviolet or electron capture detector. However, the existing technology has the following disadvantages: 1, cumbersome pretreatment, and great differences of the optimal derivation conditions of various aldehydes and ketones; 2, large dosage of solvent, which is easy to cause secondary environment pollution and is not conducive to environmental protection; 3, low sensitivity, high detection limit and poor accuracy of UV detector; 4, long analysis time and low detection efficiency, which are not conducive to the detection of a large number of samples: 5, the hydrazone compounds obtained by the reaction of DNPH with aldehydes and ketones is difficult to achieve baseline separation, and it is easy to obtain false positive detection results.
SUMMARY
An object of the present invention is to solve at least above problems, and to provide, at least, the advantages that will be described later.
Another object of the present invention is to provide a indole compound, which is easy to react with aldehydes and ketones. The reaction products are separated by ultra-high performance liquid chromatography and detected by mass spectrometry detector, and the derivatization products of indole compound and aldehydes and ketones has sensitive mass spectrometry response, good lingar relationship, low detection limit, short analysis time and accurate quantification.
Another object of the present invention is to provide a preparation method of the indole compound, which adopts known and available raw materials, and multi-step reaction to successfully synthesize a new compound that can be used for the the detection of aldehydes and ketones in water by ultra-high performance liquid chromatography-mass spectrometry.
Another object of the present invention is to provide an application of the indole compound as an aldehyde-ketone derivatization reagent in the detection of aldehydes and ketones in water environment,
In order to achieve these objects and other advantages according to the present invention, the present invention provides an indole compound of formula (I):
R4
R
2 \ O
Rs N HN—NH,
Ry Rs (1) wherein R; and R; are each independently F, R; and Ry are each independently H, and Rs is
CH.
The present invention also provides a preparation method of the indole compound, including the following steps: step one, dissolving 4.6-difluoro-1H-indole-2-formic acid into anhvdrous methanol, adding a catalytic amount of concentrated sulfuric acid under stirring, heating to reflux, reacting for 3 h, cooling, filtering and washing with petroleum ether to obtain methyl 4,6-difluoro-1H4-indole-2-carboxylate: step two, performing methvlation of methyl 4,6-difluoro-1H-indole-2-carboxyvlate to obtain methyl 4,6-difluoro-1-methyl-1H-indole-2-carboxylate; step three, reacting of methyl 4,6-difluoro -1-methyl-1H-indole-2-carboxylate with hydrazine hydrate to obtain a compound of formula (I).
Preferably, wherein the step two specifically includes: dissolving a product obtained in the step one into N, N-dimethylformamide, stirring in an ice water bath, adding sodium hydride and iodomethane, reacting in the ice water bath to room temperature for 2 h, adding ice water for quenching the reaction, washing with saturated salt water, drying. and performing column chromatography to obtain a methylation product.
Preferably, wherein the step three specifically includes: issolving the methylation product obtained in the step two into anhydrous ethanol, adding hydrazine hydrate, reacting under reflux for 5 h, cooling to room temperature, removing solvent by suction filtration, and washing with petroleum ether.
Preferably, wherein a molar ratio of the product obtained in the step one, sodium hydride and 1odomethane is 1:3:3.
The present invention also provides an application of the indole compound as an aldehyde-ketone derivatization reagent in the detection of aldehydes and ketones m water environment.
The present invention includes at least the following substantial improvements and beneficial effects:
I. The indole compound of the present invention contains hydrazide groups, which can react rapidly with aldehydes and ketones. The ionization ability of tertiary amine is improved by introducing methyl or deuterated methyl to a N atom, thus improving the detection sensitivity of mass spectrometry. 2. The preparation method of the present invention has easily accessible raw material, simple synthetic conditions, high preparation yield, and easily ionized product. 3. The indole compound of the present invention can be applied for the detection of aldehydes and ketones in the water environment, and has sensitive mass spectrum response, good reproducibility, and low detection limit.
Other advantages, objects, and features of the present invention will be shown in part through the following description, and in part will be understood by those skilled in the art from study and practice of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a nuclear magnetic resonance hydrogen spectrum of a compound 1 according to embodiment 1 of the present invention.
Fig. 2 is a nuclear magnetic resonance carbon spectrum of the compound 1 according to embodiment 1 of the present invention.
Fig. 3 is a nuclear magnetic resonance hydrogen spectrum of a compound 2 according to embodiment 1 of the present invention.
Fig. 4 is a nuclear magnetic resonance carbon spectrum of the compound 2 according to embodiment | of the present invention.
Fig. 5 is a nuclear magnetic resonance hydrogen spectrum of a target compound DFICH according to embodiment | of the present invention.
Fig. 6 is a nuclear magnetic resonance carbon spectrum of the target compound DFICH according to embodiment | of the present invention.
Fig. 7 is a nuclear magnetic resonance hydrogen spectrum of a reaction product of DFICH and benzaldehyde according to embodiment 1 of the present invention.
Fig. 8 is a nuclear magnetic resonance carbon spectrum of the reaction product of DFICH and benzaldehyde according to embodiment 1 of the present invention.
Fig. 9 is an ultra-high performance liquid chromatography-triple quadrupole mass spectrometry of the target compound DFICH in the detection of aldehydes and ketones according to embodiment 1 of the present invention.
DETAILED DESCRIPTION
The present invention will now be described in further detail concerning the embodiments, to enable a person skilled in the field to practice regarding the literal description of the specification.
It should be noted that terms such as "having", "including" and "comprising" as used herein do not exclude presence or addition of one or more other elements or combinations thereof.
It should be noted that the experimental methods described in the following embodiments are all conventional methods unless otherwise specified, and the reagents and materials are commercially available unless otherwise specified.
Embodiment
An indole compound DFICH with a formula as follows:
F oer
E N HN-NH, 5 A specific synthesis route is as follows:
F F F
O4 CH3OH 004 NaH, CH O4
E N OH conc.H,SO, E N O— DME E N O— 1 2
E
NH,NH,.H,0 One
EtOH, reflux ~~ F N HNN,
DFICH
A specific preparation method is as follows: step one, synthetise of a compound 1 (methyl 4,6-difluoro -1H-indole-2-carboxylate) 4,6-d difluoro -1H-indole-2-formic acid (0.79 g, 4.00 mmol) 1s dissolved into anhydrous methanol (15 mL), the solution is allowed to stir, a catalytic amount of concentrated sulfuric acid is added, the reaction mixture is heated to reflux and then is detected with TLC. After 3 h, the reaction is stopped, the reaction mixture is cooled. filtered, washed with petroleum ether and dried to obtain a white solid compound 1 (0.80 g, 94.7%). The nuclear magnetic resonance hydrogen spectrum of the compound 1 is shown as Fig. 1 and the nuclear magnetic resonance carbon spectrum is shown as Fig. 2.
MS (ESI) m/z: 212 (M+H°, 100); 'H NMR (300 MHz, DMSO-d) & 12.39 (s. 1H). 7.18 (d, J = 1.4 Hz, IH), 7.04 (d. J = 9.0 Hz, 1H), 6.95 (td, J = 10.4, 1.7 Hz, IH), 3.88 (s, 3H). ’C NMR (75
MHz, DMSO-d) 6 162.14, 161.98, 161.46, 158.96, 158.80, 158.16, 157.95, 154.84, 154.63, 139.08. 138.90, 138.71, 128.67, 128.63, 113.65, 113.35, 103.85, 96.36, 96.27, 95.96, 95.44, 9538, 95.10, 95.03, 52.47. step two, synthesis of compound 2 (methyl 4,6-difluoro-1-methyl1-1#-indole-2-carboxylate) the compound 1 (0.64 g, 3.00 mmol) is dissolved in DMF (10 mL) at 0°C, is fully stirred, and
NaH (0.22 g, 9.00 mmol) and iodomethane (1.27 g, 9.00 mmol) are added. The reaction mixture is stirred in a ice bath to room temperature for 2 h until TLC indicated no more starting material, and a small amount of ice water is added to quench the reaction. The reaction mixture is washed with brine (20 mL=4)}, is dried, 1s concentrated, and is rapidly purified by silica gel chromatography to obtain a white solid compound 2 (0.63 g. 93.4%). The nuclear magnetic resonance hydrogen spectrum of the compound 2 is shown as Fig. 3 and the nuclear magnetic resonance carbon spectrum is shown as Fig. 4.
MS (ESI) m/z: 226 (M+H", 100); 'H NMR (300 MHz, DMSO-4s) 6 7.43 (d. J = 9.3 Hz, 1H), 7.27 (s, IH), 7.00 (td, J = 10.3, 1.9 Hz, 1H), 3.99 (s. 3H). 3.86 (s. 3H). PC NMR (75 MHz
DMSO-ds) ò 162.43, 162.27, 161.46, 159.25, 159.08, 158.06, 157.85, 157.74, 154.74, 154.53, 141.05, 140.85, 140.68, 128.89, 128.85, 112.01, 111.71, 105.53, 96.92, 96.61, 96.52, 96.21, 94.62, 94.56, 94.26, 94.20, 52.33, 32.74. step three, synthesis of compound DFICH (4,6-difluoro-1-methyl-14-indole-2-hydrazide) the compound 2 (0.45 g. 2 mmol) is dissolved in anhydrous ethanol, and hydrazine hydrate is added. The reaction mixture is heated to reflux for 5 h until no more starting material. The reaction mixture is cooled to room temperature to generate white precipitate. The white precipitate is filtered and washed with petroleum ether to obtain white flocculent solid compound DFICH (0.37g, 82.2%).
The NMR hydrogen spectrum of the compound DFICH is shown in Fig. 5 and the NMR carbon spectrum is shown in Fig. 6.
MS (ESI) m/z: 226 (M+H', 100); melting point, 153.7°C-155.1°C; 'H NMR (300 MHz.
DMSO-ds) 6 9.85 (s, IH), 7.35 (d, J = 9.4 Hz, 1H), 7.08 (s, 1H), 6.95 (s, IH). 4.58 (s. 2H), 3.96 (s. 3H). °C NMR (75 MHz, DMSO-d) 3 161.46, 161.32, 158.30, 158.13, 157.63, 157.42, 154.33, 154.13, 140.28, 140.09. 139.91, 132.45, 112.06, 111.77, 99.89, 96.01, 95.92, 95.61, 94.30, 94.24, 93.94, 93.88, 32.47. HRMS (ES+) caled for C10H10F2N30 (M+H)+: 226.1988, found 226. 1984.
Embodiment 2
The compound DFICH is applied for the detection of of aldehydes and ketones in water (the detection of benzaldehyde as an example)
A standard compound obtained from the reaction of DFICH with benzaldehyde is Z/E-N '- benzylidene-4,6-difluoro-1-methyl-1H-indole-2- hydrazide, whose structural formula is as follows:
F
04
E N HN-N, =
Specific detection principle is as follows:
F ; Oo i 004 RR 0
F \ HNTNH: HO, rt. 4
F N HN-N
DFICH \ V-R;(H)
R
Specific detection process is as follows (the detection of benzaldehyde as an example): step one, preparation the standard compound obtained from the reaction of DFICH with benzaldehyde the compound DFICH (0.06 g. 0.25 mmol) is dissolved in anhydrous ethanol. and excessive benzaldehvde is added. The reaction mixture is heated to 40°C for 0.5 h until no more starting material. The solvent is removed under vacuum, and the residue is purified by silica gel chromatography to obtain a white solid standard compound (0.07 g, 90.0%). The nuclear magnetic resonance hydrogen spectrum of the product obtained from the reaction of DFICH with benzaldehyde is shown as Fig. 7 and the nuclear magnetic resonance carbon spectrum is shown as
Fig. 8.
MS (ESI) m/z: 314 (M+H', 100); melting point, 142.2°C-143.5°C; 'H NMR (300 MHz.
DMSO-á) 6 11.97 (s, 1H), 8.43 (s, IH), 7.73 (s, 2H), 7.57 — 7.25 (m, 5H), 7.00 (t, J = 9.8 Hz, 1H), 4.00 (s, 3H). "C NMR (75 MHz, DMSO-d;) & 161.91, 157.90, 148.20, 141.29, 134.70, 131.99, 130.60, 129.34, 127.55, 101.66, 96.26, 94.51, 94.16, 56.48, 32.68, 19.01. HRMS (ES+) calcd for
C17H14F2N30 (M+H)+: 313.1027, found 313.1025
The preparation process of the reference standard compounds obtained from reactions of
DFICH with other aldehydes and ketones are the same as above, and will not be repeated here. step two, the detection of aldehydes and ketones in water with DFICH
DFICH is used as a derivatization reagent in the detection of aldehydes and ketones in water environment by UHPLC-MS/MS. 2.1, preparation of a standard solution of aldehydes and ketones-DFICH mg of DFICH is added into 5% HCI aqueous solution, and is diluted to 10 mL to prepare a 500 pg/mL DFICH derivative solution. 1 mL of 10, 20, 50, 100, 200, 500, 1000 pg/mL standard aqueous solution of aldehydes and ketones is added into a 100 pL of 500 pg/mL DFICH derivative solution, and is stood at 40°C for 1 h to prepare the standard solution of aldehvdes and 5 ketones-DFICH. 2.2, pretreatment reaction of DFICH to detect aldehydes and ketones in water
I mL of a water sample is added into the 100 pL of 500 pg/mL. DFICH derivative solution, and is stood at 40°C for 1 h. 2.3, instrument conditions 2.3.1, ultra-high performance liquid chromatographic conditions
Flow speed: 0.5 mL/min, column temperature: 40°C, injection volume: 5 uL, mobile phase: 50% acetonitrile and 50% water. 2.3.2, mass spectrum conditions
Positive ion mode, capillary voltage: 2.8 kV, ion source temperature: 120°C; atomization temperature: 350°C; atomized gas flow rate: 800 L/h; backflushmg gas flow rate: 10 L/h; collision gas flow rate: 0.10 mL/min. The characteristic ions of the mass spectrum multi-reaction monitoring mode of aldehyde and ketone derivatives are shown as Table 1.
Table 1 retention time, characteristic ions and linear parameters of aldehyde and ketone derivatives quantitative ion qualitative 10n retention ~———————————————————————— linear related compounds parent ion (m/z)> parent ion (m/z)> time equation coefficient daughter ion (m/z) daughter ion (m/z) crotonaldehy Y=3556X+ 1.75 277.9>168.1 277.9>193.95 0.9991 de -DFICH 2530 butanone Y=3557X+ 1.80 279.9>168.1 279.9>193.95 0.9993 -DFICH 2530 pentanal Y=8260X+ 2.02 294.3>168.1 294.3>193.95 0.9992 -DFICH 2510 benzaldehyde 2.50 314.2>168.1 314.2>193.95 Y=3715X- 0.9998
-DFICH 31531 methylbenzal
Y=12274X dehyde 3.50 328.3>168.1 328.3>193.95 0.9994 +21879 -DFICH hexanal Y=1210X+ 5.18 308>168.1 308>193.95 0.9998 -DFICH 913 2.4, ultra-high performance liquid chromatography-triple quadrupole mass spectrometry
The retention time, characteristic ions and linear parameters of aldehydes and ketones - DFICH derivatives are shown as Table I, and it can be seen from Table 1 that the linear relationship of aldehydes and ketones - DFICH derivatives is good within a concentration range of 10-1000 pg/L (mass concentration is calculated by aldehydes and ketones), and a related coefficient is greater than 0.999. Total ion flow spectrum of aldehydes and ketones - DFICH derivatives is shown as Fig. 9, and spectra of crotonaldehyde - DFICH, butanone - DFICH, pentanal -DFICH, benzaldehyde -
DFICH, methylbenzaldehyde - DFICH, and hexanal - DFICH are in sequence according to the order of the retention time.
DFICH is suitable for high-throughput rapid detection of aldehvdes and ketones in water samples. The derivative product obtained by the reaction of the indole compound DFICH with aldehydes and ketones has sensitive mass spectrum response, low matrix interference and good reproducibility. All substances have reached the baseline separation, and the analysis of aldehydes and ketones can be completed within 7 minutes. Therefore, the new compound DFICH of the present invention can be applied for the detection of aldehydes and ketones in water by ultra-high performance liquid chromatography-mass spectrometry.
Comparative example 1
The derivative products of DNPH (2.4-dinitrophenylhydrazine) that is used for the detection of aldehydes and ketones in water in the prior art has low mass spectrum response sensitivity, so that liquid chromatography-ultraviolet detection is generally used as its detection method. Although liquid chromatography detection method has the advantages of quantitative accuracy and good reproducibility, the UV detector has low sensitivity. so that DNPH is only suitable for the detection of aldehydes and ketones with relatively high concentration in the water environment. In addition,
the derivative products of DNPH and aldehydes and ketones need to be extracted and concentrated in a pretreatment process. which is easy to cause the loss of target compound and poor recovery. The detection method of liquid chromatography-ultraviolet detector for the detection of aldehydes and ketones in water with DNPH has low detection limit, complicated pretreatment, many water samples and derivative solutions. long analysis time and large amount of solvent, which are not conducive to the detection of low concentration and large batches of samples.
The comparative data of the existing DNPH (2,4-dinitrophenyl hydrazine) compound for the detection of aldehydes and ketones in water and DFICH compound of the present invention for the detection of aldehydes and ketones in water are shown in Table 2.
Table 2 comparison DNPH and DFICH for the detection of aldehydes and ketones in water derivatization reagent DNPH DFICH liquid chromatography-ultraviolet liquid chromatography-mass detection mehod method spectrometry required volume of 250 mL 1 mL water samples
DNPH is prepared into a 600 mg/L DFICH is dissolved into 5% derivative solution with water and a hydrochloric acid to buffer solution of pH=3 with citric prepare a 500 mg/L reaction conditions acid and sodium citrate. 3 mL of the derivative solution, and 100 buffer solution and excessive DNPH ul. of the derivative derivative solution are added into solution is added into 1 mL 250 mL of water. of water. derivatization 40 40 temperature (°C) derivatization time (h) 1 1 mL of dichloromethane to extract extraction of target Non extraction, directly the reaction solution, and to dilute it compound detection with methanol detection limit{pg/L) 0.04-0.06 0.01 analysis time 40 min 7 min
Ultra-high performance liquid chromatography-mass spectrometry combines the advantages of liquid chromatography and mass spectrometry, which has higher selectivity and sensitivity, and strong qualitative and quantitative capabilities. It can be seen from Fig. 9 that the derivatization reagent of DFICH designed in the present invention has high sensitive mass spectrometry response, low detection limit, short analysis time, simple pretreatment, and few required water samples and derivative solutions, and can be used for high-throughput rapid detection of aldehvdes and ketones with low content in the water environment.
Although the embodiments of the present invention have been disclosed above, they are not limited to the applications previously mentioned in the specification and embodiments and can be applied in various fields suitable for the present invention. For an ordinary skilled person in the field, other changes may be easily achieved. Therefore, without departing the general concept defined by the claims and their equivalents, the present invention is not limited to particular details and embodiments shown and described herein.

Claims (6)

CONCLUSIESCONCLUSIONS I. Indoolverbinding, gekenmerkt doordat de indoolverbinding een formule heeft (I): R4 R 2 A oO Rs N HN—NH, R, Rs 1) waarbij R; en R; elk onafhankelijk F, R, enR,4 elk onafhankelijk H, en Rs is CH; .I. Indole compound, characterized in that the indole compound has a formula (I): R4 R 2 A oO Rs N HN—NH, R, Rs 1) where R; and R; each independently F, R, and R,4 each independently H, and Rs is CH; . 2. Bereidingswerkwijze van de indoolverbindmg volgens een van de conclusie 1, gekenmerkt doordat de bereidings werkwijze de volgende stappen omvat: stap één, het oplossen van 4, 6-difluor-1H-indool-2-methaanzuur in watervrij methanol, het toevoegen van cen katalytische hoeveelheid geconcentreerd zwavelzuur onder het roeren. het verwarmen aan terugvloeiing, het reageren gedurende 3 uur, het koelen, het filtreren en het wassen met petroleumether om methyl 4.6-difluor-1H-1indool-2-carboxylaat te verkrijgen: stap twee, het uitvoeren van methylatie van methyl 4,6-difluor-1H-indool-2-carboxylaat om methyl 4,6-difluor-1-methyl-1H-indool-2-carboxylaat te verkrijgen: stap drie, het reageren van methyl 4.6-difluor -1-methyl-1H-indool-2-carboxylaat met hydrazine hydraat om een verbinding van Formule (I) te verkrijgen.2. Preparation method of the indole compound according to any one of claim 1, characterized in that the preparation method comprises the following steps: step one, dissolving 4,6-difluoro-1H-indole-2-methanoic acid in anhydrous methanol, adding c catalytic amount of concentrated sulfuric acid while stirring. heating at reflux, reacting for 3 hours, cooling, filtering and washing with petroleum ether to obtain methyl 4,6-difluoro-1H-1indole-2-carboxylate: step two, carrying out methylation of methyl 4,6- difluoro-1H-indole-2-carboxylate to obtain methyl 4,6-difluoro-1-methyl-1H-indole-2-carboxylate: step three, reacting methyl 4,6-difluoro-1-methyl-1H-indole- 2-carboxylate with hydrazine hydrate to obtain a compound of Formula (I). 3. Bereidingswerkwijze volgens conclusie 2, gekenmerkt doordat stap twee specifiek omvat: het oplossen van een m stap één verkregen product m N, N-dimethylformamide, het roeren m een ijswaterbad, het toevoegen van natriumhydride en jodomethaan, het reageren in het ijswaterbad op kamertemperatuur gedurende 2 uur, het toevoegen van ijswater voor het blussen van de reactive, het wassen met verzadigd zout water, het drogen, en het uitvoeren van kolomchromatografie om een methylatieproduct te verkrijgen.Preparation method according to claim 2, characterized in that step two specifically comprises: dissolving a product obtained in step one in N,N-dimethylformamide, stirring in an ice-water bath, adding sodium hydride and iodomethane, reacting in the ice-water bath at room temperature for 2 hours, adding ice water to quench the reactive, washing with saturated salt water, drying, and performing column chromatography to obtain a methylation product. 4. Bereidingswerkwijze volgens conclusie 2, gekenmerkt doordat stap drie specifiek omvat: het oplossen van het methylatieproduct verkregen in stap twee in watervrije ethanol, het toevoegen van hydrazine hydraat, het reageren onder terugvloeiing gedurende 5 uur, het koelen aan kamertemperatuur, het verwijderen van oplosmiddel door zuigfiltratie, en het wassen met petroleumether.Preparation method according to claim 2, characterized in that step three specifically comprises: dissolving the methylation product obtained in step two in anhydrous ethanol, adding hydrazine hydrate, reacting under reflux for 5 hours, cooling to room temperature, removing solvent by suction filtration, and washing with petroleum ether. 5. Bereidingswerkwijze volgens conclusie 3, gekenmerkt doordat een molaire verhouding van het in stap één verkregen product, natriumhyvdride en jodomethaan 1:3:3 is.Preparation method according to claim 3, characterized in that a molar ratio of the product obtained in step one, sodium hydride and iodomethane is 1:3:3. 6. Toepassing van de indoolverbinding volgens conclusie 1 als een aldehyde-ketonderivatiseringsreagens bij de detectie van aldehyden en ketonen in watermilieu.Use of the indole compound according to claim 1 as an aldehyde-ketone derivative reagent in the detection of aldehydes and ketones in water environments.
NL2034563A 2022-05-27 2023-04-13 Indole compound, its preparation method and application in detection of aldehydes and ketones NL2034563A (en)

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