CN111100058B - 3, 3-dicarboxylic acid ester-indoline-2-thioketone compound and synthetic method and application thereof - Google Patents

3, 3-dicarboxylic acid ester-indoline-2-thioketone compound and synthetic method and application thereof Download PDF

Info

Publication number
CN111100058B
CN111100058B CN201911158491.1A CN201911158491A CN111100058B CN 111100058 B CN111100058 B CN 111100058B CN 201911158491 A CN201911158491 A CN 201911158491A CN 111100058 B CN111100058 B CN 111100058B
Authority
CN
China
Prior art keywords
nmr
anhydrous
alkyl
indoline
formula
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.)
Active
Application number
CN201911158491.1A
Other languages
Chinese (zh)
Other versions
CN111100058A (en
Inventor
姜丽琴
姚智
蔡忠良
杨俊�
于淼
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
East China Normal University
Original Assignee
East China Normal University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by East China Normal University filed Critical East China Normal University
Priority to CN201911158491.1A priority Critical patent/CN111100058B/en
Publication of CN111100058A publication Critical patent/CN111100058A/en
Application granted granted Critical
Publication of CN111100058B publication Critical patent/CN111100058B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
    • Y02E10/00—Energy generation through renewable energy sources
    • Y02E10/50—Photovoltaic [PV] energy
    • Y02E10/542—Dye sensitized solar cells

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Indole Compounds (AREA)

Abstract

The invention discloses a 3, 3-dicarboxylic ester-indoline-2-thioketone compound and a synthesis method thereof, which takes N-alkyl/N-aryl thioamide shown in a formula (1) as a raw material, and generates dehydrogenation coupling reaction of intramolecular C (sp 2) -H and C (sp 3) -H in an organic solvent at the temperature of 50-80 ℃ in the presence of an oxidant, a catalyst and alkali to obtain the 3, 3-dicarboxylic ester-indoline-2-thioketone compound. The synthesis method of the 3, 3-dicarboxylic ester-indoline-2-thioketone compound has the advantages of good yield, simplicity, high efficiency, convenience in post-treatment and the like by controlling conditions. The invention also discloses application of the 3, 3-dicarboxylic ester-indoline-2-thioketone compound in synthesizing medicines and photoelectric materials.

Description

3, 3-dicarboxylic acid ester-indoline-2-thioketone compound and synthetic method and application thereof
Technical Field
The invention belongs to the field of synthetic medicine and chemical engineering, and mainly relates to a 3, 3-dicarboxylic acid ester-indoline-2-thioketone compound, a synthetic method and application thereof.
Background
2, 3-indoline is also called indoline, the most main application is an intermediate for synthesizing medicines and pesticides, triethyl benzyl ammonium chloride is used as a catalyst to react with aromatic aldehyde to synthesize a series of (E) -3-benzylidene-2, 3-indoline-2-ketone derivatives, and sodium bromfenac can also be synthesized, so that the compound is a non-steroidal anti-inflammatory drug and has a powerful analgesic effect. The indoline dye is used as a sensitizer of the quasi-solid dye-sensitized solar cell and has good photoelectric conversion performance. The series of derivatives of the compound have good application prospect, so that the development of a novel indoline-2-thioketone compound is an attempt with great application value in the field.
Disclosure of Invention
The invention aims to provide a 3, 3-dicarboxylic ester-indoline-2-thioketone compound and a synthesis method thereof aiming at the defects of the prior art, wherein the synthesis method adopts cheap and easily-obtained catalyst, oxidant and alkali, and synthesizes the 3, 3-dicarboxylic ester-indoline-2-thioketone compound efficiently and rapidly with moderate to good yield. The method has the advantages of simple operation, rapid reaction, convenient treatment, good yield and certain functional group tolerance.
The invention provides a 3, 3-dicarboxylic ester-indoline-2-thioketone compound and a synthetic method thereof.
The 3, 3-dicarboxylic ester-indoline-2-thioketone compound provided by the invention has the following structure (2):
Figure BDA0002285435600000011
wherein,
R 1 hydrogen, alkyl, ester, acyl, halogen, alkoxy, sulfonamide, etc.;
R 2 alkyl, benzyl, substituted alkyl, etc.;
R 3 、R 4 independently alkyl, benzyl, etc.
Preferably, R 1 Hydrogen, methyl, methoxy, sulfonamide, halogen, ethyl formate, acetyl, etc.;
R 2 methyl, isopropyl, n-hexyl, benzyl, 3-methoxypropyl, etc.;
R 3 、R 4 independently methyl, ethyl, isopropyl, benzyl, etc.
The invention provides a synthesis method of a 3, 3-dicarboxylic ester-indoline-2-thioketone compound, which comprises the following steps: in an organic solvent, under the temperature condition of 50-80 ℃, the N-alkyl/N-aryl thioamide shown in the formula (1), an oxidant, a catalyst and alkali carry out dehydrogenation coupling reaction of C (sp 2) -H and C (sp 3) -H in molecules to obtain the 3, 3-dicarboxylic ester-indoline-2-thioketone compound shown in the formula (2).
The reaction process is shown as a reaction formula (I):
Figure BDA0002285435600000021
wherein R is 1 Hydrogen, alkyl, ester, acyl, halogen, alkoxy, sulfonamide, etc.;
R 2 alkyl, benzyl, substituted alkyl, etc.;
R 3 、R 4 independently an alkyl group, benzyl group, and the like.
Preferably, R 1 Hydrogen, methyl, methoxy, sulfonamide, halogen, ethyl formate, acetyl, etc.;
R 2 methyl, isopropyl, n-hexyl, benzyl, 3-methoxypropyl, etc.;
R 3 、R 4 independently methyl, ethyl, isopropyl, benzyl, etc.
Wherein the molar ratio of the N-alkyl/N-aryl thioamide represented by the formula (1) to the oxidizing agent is 1:2; the molar ratio of N-alkyl/N-aryl thioamide to catalyst is 1:0.1; the molar ratio of N-alkyl/N-aryl thioamide to base is 1: (1.2-3); preferably, 1: 3. 1:2.5, 1:2. 1:1.5, 1: 1.2; further preferably 1:2.
wherein the oxidant is potassium persulfate, sodium persulfate, DDQ, iodobenzene acetate, copper acetate, DTBP, TBHP, silver oxide and silver carbonate; preferably, sodium persulfate.
Wherein the catalyst is anhydrous cobalt bromide, anhydrous cobalt chloride, anhydrous cobalt acetate, cobalt acetylacetonate (II) and cobalt tris (2, 4-pentanedionate) (III); preferably, it is anhydrous cobalt bromide.
Wherein the alkali is potassium carbonate, potassium phosphate, cesium carbonate, potassium hydroxide, potassium tert-butoxide, triethylamine, DBU and DIPEA; preferably, DBU.
Wherein the organic solvent is anhydrous acetonitrile, anhydrous tetrahydrofuran, anhydrous toluene, anhydrous N, N-dimethylformamide, anhydrous dimethyl sulfoxide, anhydrous 1, 1-dichloroethane, anhydrous 1, 4-dioxane, preferably anhydrous acetonitrile.
Wherein the reaction temperature is 50 ℃ or 80 ℃; preferably 50 deg.c.
Wherein the reaction time is 1 to 2 hours.
Wherein, the method also comprises the steps of post-treatment and column chromatography separation and purification; wherein, the separation and purification is to use ethyl acetate/petroleum ether mixed solvent as eluent to carry out column chromatography separation, and the volume ratio of the ethyl acetate to the petroleum ether mixed solvent is 1.
In one embodiment, the method of the invention comprises: an N-alkyl/N-aryl thioamide represented by formula (1), an oxidizing agent, a catalyst and a base are subjected to intramolecular dehydrogenation coupling reaction at 50-80 ℃ in an organic solvent. TLC monitoring till the raw material reaction is finished, filtering to remove solid, concentrating the filtrate under reduced pressure, and performing column chromatography on the residue by using a mixed solvent of petroleum ether/ethyl acetate to obtain the 3, 3-dicarboxylic ester-indoline-2-thioketone compound shown in the formula (2).
The invention provides a method for synthesizing a 3, 3-dicarboxylic ester-indoline-2-thioketone compound, which takes N-alkyl/N-aryl thioamide shown in formula (1) as a raw material, and generates dehydrogenation coupling reaction of intramolecular C (sp 2) -H and intramolecular C (sp 3) -H in an organic solvent at the temperature of 50-80 ℃ in the presence of a catalyst, an oxidant and alkali to obtain the 3, 3-dicarboxylic ester-indoline-2-thioketone compound; after post-treatment and column chromatography separation and purification, the purified 3, 3-dicarboxylic ester-indoline-2-thioketone compound is obtained.
The invention also provides application of the 3, 3-dicarboxylic acid ester-indoline-2-thioketone compound in synthesizing medicines and photoelectric materials.
The invention adopts raw materials which are easy to prepare, and simply and efficiently constructs the 3, 3-dicarboxylic ester-indoline-2-thioketone compound by dehydrogenation coupling reaction of C (sp 2) -H and C (sp 3) -H in molecules. The method has the advantages of simple operation, rapid and efficient reaction, convenient post-treatment and high yield up to 90%. The 3, 3-dicarboxylic acid ester-indoline-2-thioketone compound synthesized by the invention is a new compound, is synthesized for the first time, and can be applied to the fields of synthetic medicines, photoelectric materials and the like.
Drawings
FIGS. 1 to 26 are respectively nuclear magnetic copolymers of 3, 3-dicarboxylate-indoline-2-thione compounds synthesized according to examples 1 to 26 of the present inventionVibration device 1 H NMR、 13 A C NMR spectrum;
Detailed Description
The present invention will be described in further detail with reference to specific embodiments and drawings, and the present invention is not limited to the embodiments. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected.
Example 1
Figure BDA0002285435600000041
Dimethyl 2- (methyl (phenyl) carbamoyl) malonate (56.2mg, 0.2mmol), anhydrous cobalt bromide (4.4mg, 0.02mmol), DBU (60.9mg, 0.4mmol) and sodium persulfate (95.2 mg,0.4 mmol) were added to a reaction flask, anhydrous acetonitrile 4mL was added, reaction was conducted at 50 ℃ for 1 hour, TLC detection was carried out for complete consumption of the starting material, insoluble solids were removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 40.4mg of a pure product. The structure is shown as formula (2-1). The yield was 72%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 1, and the product: 1 H NMR(500MHz,CDCl 3 )δ7.53 (d,J＝7.4Hz,1H),7.44(td,J＝7.8,1.0Hz,1H),7.22(t,J＝7.6Hz,1H),7.00(d,J＝ 7.9Hz,1H),3.79(s,6H),3.63(s,3H). 13 C NMR(126MHz,CDCl 3 )δ193.68,165.22, 145.85,130.23,127.95,125.67,124.78,109.83,75.13,53.87,31.79.
HRMS(EI)m/z calculated for C 13 H 13 NO 4 S[M] + 279.0565,found 279.0567.
example 2
Figure BDA0002285435600000042
In this example, the experimental method is basically the same as in example 1, and the raw material used in this example is 2- ((4-methoxyphenyl) ((s))Methyl) carbamoyl) malonic acid dimethyl ester, reacting at 50 ℃ for 1 hour to obtain the product shown as a structural formula (2-2). The yield was 77%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 2, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.34(s,1H),7.23(d,J＝8.0 Hz,1H),6.90(d,J＝8.1Hz,1H),3.79(s,6H),3.61(s,3H),2.38(s,3H). 13 C NMR (151MHz,CDCl 3 )δ193.20,165.40,143.64,134.87,130.70,127.96,126.27,109.60, 75.09,53.88,31.88,21.19.
HRMS(EI)m/z calculated for C 14 H 15 NO 5 S[M] + 309.0671,found 309.0674.
example 3
Figure BDA0002285435600000051
This example was conducted in substantially the same manner as in example 1 except that dimethyl 2- (methyl (p-tolyl) carbamoyl) malonate was used as a starting material, and the reaction was conducted at 50 ℃ for 1 hour to obtain a product represented by the following structural formula (2-3). The yield was 79%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 3, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.34(s,1H),7.23(d,J＝8.0Hz, 1H),6.90(d,J＝8.1Hz,1H),3.79(s,6H),3.61(s,3H),2.38(s,3H). 13 C NMR(151 MHz,CDCl 3 )δ193.20,165.39,143.64,134.87,130.70,127.96,126.27,109.60, 75.10,53.88,31.88,21.19.
HRMS(EI)m/z calculated for C 14 H 15 NO 4 S[M] + 293.0722,found 293.0720.
example 4
Figure BDA0002285435600000052
This example was carried out in substantially the same manner as example 1 except that the starting material used in this example was 2- ((4- (N, 4-dimethylphenylsulfonamido) phenyl) (methyl) aminomethylcarbonyl) Dimethyl malonate at 50 ℃ for 1.5 hours to obtain a product shown as a structural formula (2-4). The yield was 74%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 4, and the product: 1 H NMR(600MHz,CDCl 3 ) δ7.33(d,J＝7.8Hz,2H),7.21(d,J＝9.8Hz,1H),7.18(d,J＝7.8Hz,2H),7.09(s, 1H),6.87(d,J＝8.4Hz,1H),3.70(s,6H),3.54(s,3H),3.08(s,3H),2.35(s,3H). 13 C NMR(151MHz,CDCl 3 )δ193.66,164.79,144.75,143.81,138.50,133.01,129.60, 129.52,128.10,127.91,123.71,109.73,74.86,53.96,38.15,31.89,21.61.
HRMS(EI)m/z calculated for C 21 H 22 N 2 O 6 S 2 [M] + 462.0919,found 462.0915.
example 5
Figure BDA0002285435600000061
This example was conducted in substantially the same manner as example 1 except that dimethyl 2- ((4-fluorophenyl) (methyl) carbamoyl) malonate was used as the starting material, and the reaction was carried out at 50 ℃ for 1.5 hours to obtain a product represented by the formula (2-5). The yield was 69%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 5, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.29(dd,J＝7.6,2.6Hz,1H), 7.16(td,J＝8.7,2.6Hz,1H),6.95(dd,J＝8.7,4.0Hz,1H),3.81(s,6H),3.62(s, 3H). 13 C NMR(151MHz,CDCl 3 )δ193.11,164.75,161.20,159.58,142.00,129.23(d, J＝9.2Hz),116.93(d,J＝24.0Hz),114.01(d,J＝26.0Hz),110.39(d,J＝8.6Hz), 75.02,54.08,31.96.
HRMS(EI)m/z calculated for C 13 H 12 FNO 4 S[M] + 297.0471,found 297.0469.
example 6
Figure BDA0002285435600000062
The experimental procedure of this example was substantially the same as example 1, except that dimethyl 2- ((4-chlorophenyl) (methyl) carbamoyl) malonate was used as the starting material in this example, and the reaction time was 2 hours at 50 ℃ to obtain the product represented by the formula (2-6). The yield was 65%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 6, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.51(d,J＝1.8Hz,1H),7.41 (dd,J＝8.4,1.9Hz,1H),6.93(d,J＝8.4Hz,1H),3.82(s,6H),3.61(s,3H). 13 C NMR (151MHz,CDCl 3 )δ193.22,164.71,144.47,130.50,130.33,129.16,126.20,110.58, 74.89,54.12,31.89.
HRMS(EI)m/z calculated for C 13 H 12 ClNO 4 S[M] + 313.0176,found 313.0172.
example 7
Figure BDA0002285435600000071
The experimental procedure of this example was substantially the same as in example 1, except that dimethyl 2- ((4-bromophenyl) (methyl) carbamoyl) malonate was used as the starting material in this example, and the reaction was carried out at 50 ℃ for 1 hour to obtain the product represented by the formula (2-7). The yield was 65%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 7, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.65(d,J＝1.8Hz,1H),7.56 (dd,J＝8.4,1.9Hz,1H),6.88(d,J＝8.4Hz,1H),3.81(s,6H),3.60(s,3H). 13 C NMR(151MHz,CDCl 3 )δ193.16,164.71,144.95,133.22,129.45,128.91,117.85, 111.02,74.86,54.13,31.86.
HRMS(EI)m/z calculated for C 13 H 12 BrNO 4 S[M] + 356.9670,found 356.9668.
example 8
Figure BDA0002285435600000072
The experimental methods of the present examples are substantially the same as those of the examples1, the raw material adopted in the example is 2- ((4-iodophenyl) (methyl) aminomethylsulfonyl) malonic acid dimethyl ester, the reaction time is 2 hours at 50 ℃, and the obtained product is shown as a structural formula (2-8). The yield was 42%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 8, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.74(d,J＝1.4Hz,1H),7.68(dd, J＝8.3,1.5Hz,1H),6.69(d,J＝8.3Hz,1H),3.74(s,6H),3.52(s,3H). 13 C NMR (151MHz,CDCl 3 )δ193.15,164.72,145.65,139.12,134.41,129.73,111.44,87.87, 74.79,54.06,31.74.
HRMS(EI)m/z calculated for C 13 H 12 INO 4 S[M] + 404.9532,found 404.9534.
example 9
Figure BDA0002285435600000073
This example was conducted in substantially the same manner as in example 1, using dimethyl 2- ((4- (ethoxycarbonyl) phenyl) (methyl) carbamoyl) malonate (70.6 mg, 0.2mmol), anhydrous cobalt bromide (4.4 mg, 0.02mmol), DBU (76.1mg, 0.5mmol), sodium persulfate (95.2 mg,0.4 mmol) and acetonitrile (4 mL) as starting materials, and reacting at 80 ℃ for 1 hour to obtain the product represented by the structural formula (2-9). The yield was 63%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 9, and the product: 1 H NMR(600MHz,CDCl 3 )δ8.10(dd,J＝6.0,1.6Hz,2H),6.97(d,J＝8.8 Hz,1H),4.31(q,J＝7.1Hz,2H),3.74(s,6H),3.58(s,3H),1.33(t,J＝7.1Hz,3H). 13 C NMR(151MHz,CDCl 3 )δ194.75,165.74,164.80,149.31,132.59,127.83, 127.06,126.83,109.39,74.80,61.33,54.09,31.94,14.39.
HRMS(EI)m/z calculated for C 16 H 17 NO 6 S[M] + 351.0777,found 351.0779.
example 10
Figure BDA0002285435600000081
This example was conducted in substantially the same manner as in example 1, using dimethyl 2- ((4-acetylphenyl) (methyl) carbamoyl) malonate (64.6 mg, 0.2mmol), anhydrous cobalt bromide (4.4 mg, 0.02mmol), DBU (76.1mg, 0.5mmol), sodium persulfate (95.2 mg,0.4 mmol) and acetonitrile (4 mL) as starting materials, and reacting at 80 ℃ for 1 hour to obtain the product represented by the structural formula (2-10). The yield was 81%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 10, and the product: 1 H NMR(600MHz,CDCl 3 )δ8.04(s,1H),8.02(d,J＝8.4Hz,1H),7.00(d, J＝8.3Hz,1H),3.74(s,6H),3.58(s,3H),2.54(s,3H). 13 C NMR(151MHz,CDCl 3 ) δ196.38,194.85,164.77,149.44,133.82,131.60,128.10,125.71,109.49,74.80, 54.13,31.95,26.66.
HRMS(EI)m/z calculated for C 15 H 15 NO 5 S[M] + 321.0671,found 321.0675.
example 11
Figure BDA0002285435600000091
This example was conducted in substantially the same manner as in example 1, using dimethyl 2- ((2-methoxyphenyl) (methyl) carbamoyl) malonate (62.2 mg,0.2 mmol), anhydrous cobalt bromide (4.4 mg, 0.02mmol), DBU (76.1mg, 0.5mmol), sodium persulfate (95.2 mg,0.4 mmol) and acetonitrile (4 mL) as starting materials, and reacting at 80 ℃ for 2 hours to obtain the product represented by the structural formula (2-11). The yield was 61%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 11, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.11–7.04(m,2H),6.91(d,J＝8.0Hz,1H), 3.87(s,3H),3.84(s,3H),3.71(s,6H). 13 C NMR(151MHz,CDCl 3 )δ193.18,165.37, 145.02,133.86,129.55,125.68,117.97,113.72,75.31,56.08,53.87,35.73.
HRMS(EI)m/z calculated for C 14 H 15 NO 5 S[M] + 309.0671,found 309.0668.
example 12
Figure BDA0002285435600000092
This example was conducted in substantially the same manner as in example 1, using dimethyl 2- (methyl (o-tolyl) carbamoyl) malonate (59.0 mg,0.2 mmol), anhydrous cobalt bromide (4.4 mg, 0.02mmol), DBU (76.1mg, 0.5 mmol), sodium persulfate (95.2 mg,0.4 mmol) and acetonitrile (4 mL) as starting materials, and reacted at 80 ℃ for 1 hour to obtain the product represented by the structural formula (2-12). The yield was 69%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 12, and the product: 1 H NMR(600 MHz,CDCl 3 )δ7.29(d,J＝7.4Hz,1H),7.09(d,J＝7.6Hz,1H),7.02(t,J＝7.5Hz, 1H),3.88(s,3H),3.71(s,6H),2.58(s,3H). 13 C NMR(151MHz,CDCl 3 )δ194.46, 165.51,143.91,134.26,128.47,124.73,123.59,120.97,74.91,53.86,35.65,19.80.
HRMS(EI)m/z calculated for C 14 H 15 NO 4 S[M] + 293.0722,found 293.0723.
example 13
Figure BDA0002285435600000101
The experimental procedure of this example was substantially the same as in example 1, the starting material used in this example was dimethyl 2- ((3-methoxyphenyl) (methyl) carbamoyl) malonate, and the reaction time was 1 hour at 50 ℃ to obtain the product represented by the formula (2-13). The yield was 40%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 13, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.34(d,J＝8.3Hz, 1H),6.64(d,J＝8.3Hz,1H),6.48(s,1H),3.79(s,3H),3.72(s,6H),3.53(s,3H). 13 C NMR(151MHz,CDCl 3 )δ194.66,165.54,161.70,147.15,126.26,119.71,109.02, 97.39,74.52,55.80,53.84,31.83.
HRMS(EI)m/z calculated for C 14 H 15 NO 5 S[M] + 309.0671,found 309.0674.
example 14
Figure BDA0002285435600000102
The experimental procedure of this example was substantially the same as in example 1, except that dimethyl 2- ((3-chlorophenyl) (methyl) carbamoyl) malonate was used as the starting material in this example, and the reaction time was 1 hour at 50 ℃ to obtain a product represented by the following structural formula (2-14). The yield was 20%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 14, and the product: 1 H NMR(500MHz,CDCl 3 )δ7.37(d,J＝8.1Hz,1H),7.12 (dd,J＝8.1,1.7Hz,1H),6.93(d,J＝1.7Hz,1H),3.73(s,6H),3.53(s,3H). 13 C NMR(126MHz,CDCl 3 )δ194.13,164.85,146.93,136.32,126.54,126.10,124.62, 110.47,74.67,54.06,31.85.
HRMS(EI)m/z calculated for C 13 H 12 ClNO 4 S[M] + 313.0176,found 313.0181.
example 15
Figure BDA0002285435600000103
This example was conducted in substantially the same manner as in example 1 except that dimethyl 2- ((3, 5-dimethoxyphenyl) (methyl) aminomethylcarbamoyl) malonate was used as a starting material, and a reaction was carried out at 50 ℃ for 1 hour to obtain a product represented by the following structural formula (2-15). The yield was 90%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 15, and the product: 1 H NMR(500MHz,CDCl 3 )δ6.21(d,J＝1.8Hz, 1H),6.15(d,J＝1.9Hz,1H),3.79(s,3H),3.75(s,3H),3.66(s,6H),3.50(s,3H). 13 C NMR(126MHz,CDCl 3 )δ195.57,164.56,163.06,156.64,148.18,107.82,94.45, 89.63,73.44,55.92,55.82,53.48,32.07.
HRMS(EI)m/z calculated for C 15 H 17 NO 6 S[M] + 339.0777,found 339.0780.
example 16
Figure BDA0002285435600000111
The experimental procedure of this example was substantially the same as in example 1, the starting material used in this example was diethyl 2- (methyl (phenyl) carbamoyl) malonate, and the reaction time was 1 hour at 50 ℃ to obtain the product represented by formula (2-16). The yield was 77%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 16, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.47(d,J＝7.5Hz,1H),7.35(t,J＝7.8 Hz,1H),7.14(t,J＝7.6Hz,1H),6.93(d,J＝7.9Hz,1H),4.19(q,J＝7.1Hz,4H), 3.54(s,3H),1.19(t,J＝7.1Hz,6H). 13 C NMR(151MHz,CDCl 3 )δ193.84,164.75, 145.86,130.10,128.15,125.69,124.65,109.81,75.22,62.91,31.76,13.89.
HRMS(EI)m/z calculated for C 15 H 17 NO 4 S[M] + 307.0878,found 307.0875.
example 17
Figure BDA0002285435600000112
This example was conducted in substantially the same manner as in example 1 except that dibenzyl 2- (methyl (phenyl) carbamoyl) malonate was used as a starting material, and the reaction was conducted at 50 ℃ for 1.5 hours to obtain a product represented by the formula (2-17). The yield was 70%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 17, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.35(d,J＝7.5Hz,1H),7.31(t, J＝7.8Hz,1H),7.23–7.19(m,6H),7.18–7.14(m,4H),7.06(t,J＝7.6Hz,1H), 6.87(d,J＝7.9Hz,1H),5.15–5.09(m,4H),3.50(s,3H). 13 C NMR(151MHz, CDCl 3 )δ193.30,164.50,145.94,134.91,130.26,128.51,128.34,128.00,127.75, 125.78,124.66,109.88,75.20,68.42,31.79.
HRMS(EI)m/z calculated for C 25 H 21 NO 4 S[M] + 431.1191,found 431.1193.
example 18
Figure BDA0002285435600000121
The experimental procedure of this example was substantially the same as example 1, except that diisopropyl 2- (methyl (phenyl) carbamoyl) malonate was used as the starting material and reacted at 50 ℃ for 2 hours to obtain the product represented by formula (2-18). The yield was 83%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 18, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.55(d,J＝7.5Hz,1H),7.42(t,J＝ 7.8Hz,1H),7.21(t,J＝7.6Hz,1H),6.99(d,J＝7.9Hz,1H),5.16–5.08(m,2H), 3.61(s,3H),1.28(dd,J＝14.0,6.3Hz,12H). 13 C NMR(151MHz,CDCl 3 )δ193.94, 164.22,145.86,129.97,128.32,125.71,124.49,109.74,75.22,70.65,31.70,21.42, 21.40.
HRMS(EI)m/z calculated for C 17 H 21 NO 4 S[M] + 335.1191,found 335.1189.
example 19
Figure BDA0002285435600000122
The experimental procedure of this example was substantially the same as in example 1, the starting material used in this example was dimethyl 2- (isopropyl (phenyl) carbamoyl) malonate, and the reaction time was 1.5 hours at 50 ℃ to obtain the product represented by the formula (2-19). The yield was 78%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 19, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.45(d,J＝7.5Hz,1H),7.32(t, J＝7.8Hz,1H),7.21(d,J＝8.0Hz,1H),7.12(t,J＝7.5Hz,1H),5.63(s,1H),3.71 (s,6H),1.48(d,J＝7.1Hz,6H). 13 C NMR(151MHz,CDCl 3 )δ193.41,165.38, 143.96,129.80,128.46,125.77,124.29,111.75,75.25,53.85,48.78,18.51.
HRMS(EI)m/z calculated for C 15 H 17 NO 4 S[M] + 307.0878,found 307.0882.
example 20
Figure BDA0002285435600000131
The experimental procedure of this example was substantially the same as in example 1, the starting material used in this example was dimethyl 2- (hexyl (phenyl) carbamoyl) malonate, and the reaction time was 1 hour at 50 ℃ to obtain the product represented by the formula (2-20). The yield was 75%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 20, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.45(d,J＝7.5Hz,1H),7.35(t,J＝7.7 Hz,1H),7.13(t,J＝7.5Hz,1H),6.93(d,J＝7.9Hz,1H),4.10(t,J＝7.5Hz,2H), 3.71(s,6H),1.74–1.66(m,2H),1.33(dd,J＝13.7,6.6Hz,2H),1.30–1.20(m,4H), 0.81(t,J＝6.3Hz,3H). 13 C NMR(151MHz,CDCl 3 )δ193.24,165.30,145.39, 130.17,128.18,125.66,124.60,110.03,75.23,53.84,44.91,31.45,26.49,26.00, 22.54,14.00.
HRMS(EI)m/z calculated for C 18 H 23 NO 4 S[M] + 349.1348,found 349.1351.
example 21
Figure BDA0002285435600000132
The experimental procedure of this example was substantially the same as in example 1, the starting material used in this example was dimethyl 2- ((3-methoxypropyl) (phenyl) carbamoyl) malonate, and the reaction time was 1 hour at 50 ℃ to give the product represented by the formula (2-21). The yield was 62%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 21, and the product: 1 H NMR(500MHz,CDCl 3 )δ7.45(dd,J＝7.5,0.5 Hz,1H),7.36(td,J＝7.9,1.1Hz,1H),7.13(td,J＝7.6,0.7Hz,1H),7.04(d,J＝8.0 Hz,1H),4.21(t,J＝7.0Hz,2H),3.72(s,6H),3.32(t,J＝5.8Hz,2H),3.25(s,3H), 2.04–1.97(m,2H). 13 C NMR(126MHz,CDCl 3 )δ193.36,165.29,145.66,130.23, 128.00,125.59,124.65,110.18,75.20,69.19,58.61,53.88,42.04,26.27.
HRMS(EI)m/z calculated for C 16 H 19 NO 5 S[M] + 337.0984,found 337.0981.
example 22
Figure BDA0002285435600000141
The experimental procedure of this example was substantially the same as in example 1, except that dimethyl 2- (benzyl (phenyl) aminomonoyl) malonate was used as the starting material, and the reaction was carried out at 50 ℃ for 1 hour to obtain a product represented by the following structural formula (2-22). The yield was 82%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 22, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.53(d,J＝7.5Hz,1H),7.33–7.24 (m,6H),7.17(t,J＝7.6Hz,1H),6.84(d,J＝8.0Hz,1H),5.46(s,2H),3.81(s,6H). 13 C NMR(151MHz,CDCl 3 )δ194.60,165.27,145.15,133.97,130.22,128.95, 127.97,127.88,126.91,125.53,124.81,110.79,75.34,53.94,48.15.
HRMS(EI)m/z calculated for C 19 H 17 NO 4 S[M] + 355.0878,found 355.0876.
example 23
Figure BDA0002285435600000142
The experimental procedure of this example was substantially the same as in example 1, except that dimethyl 2- (benzyl (4-methoxyphenyl) aminomethylcarbamoyl) malonate was used as the starting material, and the reaction was carried out at 50 ℃ for 1 hour to obtain a product represented by the following structural formula (2-23). The yield was 68%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 23, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.25–7.16(m,5H),7.04(d, J＝2.5Hz,1H),6.73(dd,J＝8.7,2.5Hz,1H),6.65(d,J＝8.7Hz,1H),5.35(s,2H), 3.74(s,6H),3.69(s,3H). 13 C NMR(151MHz,CDCl 3 )δ193.41,165.25,157.60, 138.65,134.00,129.22,128.93,127.87,126.92,115.08,112.16,111.25,75.37,55.88, 53.95,48.27.
HRMS(EI)m/z calculated for C 20 H 19 NO 5 S[M] + 385.0984,found 385.0980.
example 24
Figure BDA0002285435600000151
The experimental procedure of this example was substantially the same as in example 1, except that dimethyl 2- (benzyl (4-chlorophenyl) aminomethylmethionyl) malonate was used as the starting material, and the reaction time was 2 hours at 50 ℃ to obtain the product represented by the following structural formula (2-24). The yield was 68%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 24, and the product: 1 H NMR(600MHz,CDCl 3 )δ7.44(d,J＝2.0Hz,1H),7.23 (t,J＝7.2Hz,2H),7.21–7.16(m,4H),6.67(d,J＝8.5Hz,1H),5.35(s,2H),3.76(s, 6H). 13 C NMR(151MHz,CDCl 3 )δ194.12,164.74,143.72,133.59,130.54,130.29, 129.22,129.03,128.04,126.85,126.05,111.50,75.10,54.16,48.20.
HRMS(EI)m/z calculated for C 13 H 12 ClNO 4 S[M] + 313.0176,found 313.0172.
example 25
Figure BDA0002285435600000152
This example was conducted in substantially the same manner as in example 1 except that dimethyl 2- (benzyl (4-bromophenyl) aminomethylcarbonyl) malonate was used as the starting material, and the reaction was carried out at 50 ℃ for 2 hours to obtain a product represented by the following structural formula (2-25). The yield was 46%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 25, and the product: 1 H NMR(500MHz,CDCl 3 )δ7.57(d,J＝1.9Hz,1H),7.33 (dd,J＝8.4,1.9Hz,1H),7.25–7.15(m,5H),6.62(d,J＝8.5Hz,1H),5.34(s,2H), 3.76(s,6H). 13 C NMR(126MHz,CDCl 3 )δ194.03,164.73,144.18,133.55,133.16, 129.50,129.03,128.76,128.03,126.83,117.91,111.93,75.05,54.17,48.15.
HRMS(EI)m/z calculated for C 19 H 16 BrNO 4 S[M] + 432.9983,found432.9980.
example 26
Figure BDA0002285435600000161
This example was conducted in substantially the same manner as in example 1 except that dimethyl 2- (benzyl (4- (ethoxycarbonyl) phenyl) aminomonoyl) malonate (85.8mg, 0.2mmol), anhydrous cobalt bromide (4.4mg, 0.02mmol), DBU (76.1mg, 0.5mmol), sodium persulfate (95.2 mg, 0.4mmol) and acetonitrile (4 mL) were used as starting materials, and the reaction time was 2 hours at 80 ℃ to obtain the product represented by the structural formula (2-26). The yield was 59%. Nuclear magnetic resonance 1 H NMR、 13 The C NMR spectrum is shown in FIG. 26, and the product: 1 H NMR(600MHz,CDCl 3 )δ8.11(s,1H),7.96(d,J＝8.3Hz,1H),7.26– 7.22(m,2H),7.21–7.17(m,3H),6.80(d,J＝8.4Hz,1H),5.40(s,2H),4.28(q,J＝ 7.1Hz,2H),3.77(s,6H),1.30(t,J＝7.1Hz,3H). 13 C NMR(151MHz,CDCl 3 )δ 195.57,165.70,164.83,148.61,133.58,132.50,129.03,128.04,127.88,127.10, 126.82,126.71,110.27,75.01,61.30,54.12,48.19,14.37.
HRMS(EI)m/z calculated for C 22 H 21 NO 6 S[M] + 427.1090,found427.1094。

Claims (6)

1. a method for synthesizing 3, 3-dicarboxylic ester-indoline-2-thioketone compounds is characterized by comprising the following steps: in an organic solvent, under the temperature condition of 50-80 ℃, the N-alkyl/N-aryl thioamide shown in the formula (1), an oxidant, a catalyst and alkali generate dehydrogenation coupling reaction of C (sp 2) -H and C (sp 3) -H in molecules to obtain a 3, 3-dicarboxylic ester-dihydro indole-2-thioketone compound shown in the formula (2); the reaction process is shown as a reaction formula (I):
Figure FDA0003549813210000011
wherein,
R 1 hydrogen, alkyl, ester group, acyl, halogen, alkoxy, sulfonamide;
R 2 is alkyl, benzyl, substituted alkyl;
R 3 、R 4 independently is alkyl or benzyl;
the oxidant is potassium persulfate, sodium persulfate, DDQ, iodobenzene acetate, copper acetate, DTBP, TBHP, silver oxide and silver carbonate;
the catalyst is anhydrous cobalt bromide, anhydrous cobalt chloride, anhydrous cobalt acetate, cobalt acetylacetonate (II) and cobalt tris (2, 4-pentanedionate) (III);
the alkali is potassium carbonate, potassium phosphate, cesium carbonate, potassium hydroxide, potassium tert-butoxide, triethylamine, DBU and DIPEA.
2. The synthesis method according to claim 1, wherein the molar ratio of the N-alkyl/N-aryl thioamide represented by the formula (1) to the oxidizing agent is 1:2; the molar ratio of N-alkyl/N-aryl thioamide to catalyst is 1:0.1; the molar ratio of N-alkyl/N-aryl thioamide to base is 1: (1.2-3).
3. The method of claim 1, wherein the organic solvent is anhydrous acetonitrile, anhydrous tetrahydrofuran, anhydrous toluene, anhydrous N, N-dimethylformamide, anhydrous dimethylsulfoxide, anhydrous 1, 1-dichloroethane, or anhydrous 1, 4-dioxane.
4. The method of claim 1, wherein the reaction time is 1 to 2 hours.
5. The synthesis method according to claim 1, characterized in that the method further comprises the steps of post-treatment and column chromatographic separation and purification; wherein, the separation and purification is to use ethyl acetate/petroleum ether mixed solvent as eluent to carry out column chromatography separation, and the volume ratio of the ethyl acetate to the petroleum ether mixed solvent is 1.
6. The synthesis method according to claim 1, characterized in that it comprises in particular: carrying out dehydrogenation coupling reaction of intramolecular C (sp 2) -H and C (sp 3) -H on N-alkyl/N-aryl thioamide shown in a formula (1), an oxidant, a catalyst and a base in an organic solvent at 50-80 ℃; TLC monitoring till the raw material reaction is finished, filtering to remove solid, concentrating the filtrate under reduced pressure, and performing column chromatography on the residue by using a mixed solvent of petroleum ether/ethyl acetate to obtain the 3, 3-dicarboxylic ester-indoline-2-thioketone compound shown in the formula (2).
CN201911158491.1A 2019-11-22 2019-11-22 3, 3-dicarboxylic acid ester-indoline-2-thioketone compound and synthetic method and application thereof Active CN111100058B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201911158491.1A CN111100058B (en) 2019-11-22 2019-11-22 3, 3-dicarboxylic acid ester-indoline-2-thioketone compound and synthetic method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201911158491.1A CN111100058B (en) 2019-11-22 2019-11-22 3, 3-dicarboxylic acid ester-indoline-2-thioketone compound and synthetic method and application thereof

Publications (2)

Publication Number Publication Date
CN111100058A CN111100058A (en) 2020-05-05
CN111100058B true CN111100058B (en) 2023-02-07

Family

ID=70421324

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201911158491.1A Active CN111100058B (en) 2019-11-22 2019-11-22 3, 3-dicarboxylic acid ester-indoline-2-thioketone compound and synthetic method and application thereof

Country Status (1)

Country Link
CN (1) CN111100058B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112778267A (en) * 2020-12-31 2021-05-11 华东师范大学 Thiophene-3 (2H) -ketone compound and synthetic method thereof
CN114262290B (en) * 2021-12-20 2024-03-22 华东师范大学 4-methylene pyrrolidine-2-thioketone compound, and synthetic method and application thereof

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ283965B6 (en) * 1992-08-06 1998-07-15 Warner-Lambert Company 2-thioindoles, 2-indolinethiones and polysulfides, their selenium analogs and pharmaceutical preparations based thereon
DE19853558A1 (en) * 1998-11-20 2000-05-31 Aventis Res & Tech Gmbh & Co Process for the preparation of 2,3-dihydroindoles (indolines), novel 2,3-dihydroindoles and their use
EP1971496B1 (en) * 2006-01-10 2010-09-08 The Yokohama Rubber Co., Ltd. Laminate of thermoplastic polymer composition having low air permeability and pneumatic tire using same as inner liner
WO2008046087A2 (en) * 2006-10-12 2008-04-17 Xenon Pharmaceuticals Inc. Spiro compounds and their uses as therapeutic agents
US20120093793A1 (en) * 2010-08-06 2012-04-19 Slichter Sherrill J Methods of Preventing Platelet Alloimmunization and Alloimmune Platelet Refractoriness and Induction of Tolerance in Transfused Recipients
WO2017184589A1 (en) * 2016-04-18 2017-10-26 The Scripps Research Institute A versatile ligand for palladium-catalyzed meta-c-h functionalizations
CN109574904A (en) * 2018-09-20 2019-04-05 郑州大学 A kind of trifluoromethyl substituted-dihydro Benzazole compounds and preparation method thereof
CN109721523B (en) * 2018-12-24 2021-12-21 江苏理工学院 Indoline derivative and preparation method thereof
CN109836365B (en) * 2019-01-15 2021-02-26 华东师范大学 Amine thioacyl fluoride derivatives and synthetic method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
A Direct C-H/Ar-H Coupling Approach to Oxindoles, Thio-oxindoles, 3,4-Dihydro-1 H-quinolin-2-ones, and 1,2,3,4-Tetrahydroquinolines;Hurst, Timothy E等;《Chemistry - A European Journal 》;20141231;第20卷(第43期);第14065页Scheme 3以及第14068-14069页化合物16g的制备 *

Also Published As

Publication number Publication date
CN111100058A (en) 2020-05-05

Similar Documents

Publication Publication Date Title
Ju et al. Synthesis of oxindoles via visible light photoredox catalysis
CN108409747B (en) Synthetic method of 2-aminoquinoline dihydrofuran compound
CN111100058B (en) 3, 3-dicarboxylic acid ester-indoline-2-thioketone compound and synthetic method and application thereof
WO2021169359A1 (en) Benzodihydrofuro heterocyclic compound and preparation method therefor
CN111056889B (en) N-alkyl/N-aryl thioamide derivatives and synthesis method and application thereof
CN110240554B (en) Alpha-thioether aryl acetonitrile compound and synthetic method thereof
CN102863371B (en) Fluoro pyrrolin or fluoro pyrroles
CN113651788B (en) 3-aminoalkylchromone compound and preparation method thereof
CN112194608B (en) Synthesis method of visible light promoted 3-methyl-3-difluoroethyl-2-oxindole compound
Ji et al. Copper-catalyzed cyclization reaction: synthesis of trifluoromethylated indolinyl ketones
CN102531995A (en) 3,3'-disubstituted-3-hydroxy bis-indolinone derivative and preparation method and application thereof
CN110028448B (en) Preparation method of 3-hydroxy-2,3-dihydroisoquinoline-1, 4-diketone compound
CN112920072A (en) NOBIN biaryl compound and synthetic method thereof
CN113264850A (en) Synthetic method of nootropic ketonic A
CN103342674B (en) One class optical activity pyrrole derivative and synthetic method thereof
CN103539754B (en) A kind of 4-replaces the cyclisation method of-2-oxazolidone
CN111205202A (en) Quaternary carbon center-containing symmetric gem-difluoroolefin derivative and synthesis method thereof
CN114262290B (en) 4-methylene pyrrolidine-2-thioketone compound, and synthetic method and application thereof
CN111116510B (en) 2-substituted methylene dihydrobenzo [ d ] thiazole derivatives and synthesis method and application thereof
CN110590641B (en) Green preparation method of 3-hydroxyisoindole-1-ketone series compounds
CN116462619B (en) Preparation method of cyclopentenone derivative
CN109438309B (en) Z-2-selenocyanatyl alkenyl aryl sulfone compound and synthetic method thereof
CN105294517B (en) Method for preparing chiral 1, 3-diamine
CN113754597B (en) Benzhydryl piperazine compound containing linear olefin and preparation method thereof
CN115536494B (en) Synthesis method of 1- (4-bromophenyl) -1, 4-butanediol

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