CN111100058A - 3, 3-dicarboxylic ester-indoline-2-thioketone compound and synthesis method and application thereof - Google Patents

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

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CN111100058A
CN111100058A CN201911158491.1A CN201911158491A CN111100058A CN 111100058 A CN111100058 A CN 111100058A CN 201911158491 A CN201911158491 A CN 201911158491A CN 111100058 A CN111100058 A CN 111100058A
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姜丽琴
姚智
蔡忠良
杨俊�
于淼
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East China Normal University
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    • 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
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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 the dehydrogenation coupling reaction of intramolecular C (sp2) -H and intramolecular C (sp3) -H is carried out 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 ester-indoline-2-thioketone compound and synthesis 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 ester-indoline-2-thioketone compound, and 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 quickly 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,
R1hydrogen, alkyl, ester, acyl, halogen, alkoxy, sulfonamide, etc.;
R2alkyl, benzyl, substituted alkyl, etc.;
R3、R4independently alkyl, benzyl, etc.
Preferably, R1Hydrogen, methyl, methoxy, sulfonamide, halogen, ethyl formate, acetyl, etc.;
R2methyl, isopropyl, n-hexyl, benzyl, 3-methoxypropyl, etc.;
R3、R4independently 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 (sp2) -H and C (sp3) -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 is1Hydrogen, alkyl, ester, acyl, halogen, alkoxy, sulfonamide, etc.;
R2alkyl, benzyl, substituted alkyl, etc.;
R3、R4independently alkyl, benzyl, etc.
Preferably, R1Hydrogen, methyl, methoxy, sulfonamide, halogen, ethyl formate, acetyl, etc.;
R2methyl, isopropyl, n-hexyl, benzyl, 3-methoxypropyl, etc.;
R3、R4independently 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, it is 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 1-2 hours.
Wherein, the method also comprises the steps of post-treatment and column chromatography separation and purification; the separation and purification is to perform column chromatography separation by using an ethyl acetate/petroleum ether mixed solvent as an eluent, wherein the volume ratio of the ethyl acetate to the petroleum ether mixed solvent is 1: 3-1: 10.
In one embodiment, the method of the present invention comprises: the N-alkyl/N-aryl thioamide shown in the formula (1), an oxidant, a catalyst and a base are subjected to intramolecular dehydrogenation coupling reaction of C (sp2) -H and C (sp3) -H 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 separation 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 a formula (1) as a raw material, and generates dehydrogenation coupling reaction of intramolecular C (sp2) -H and intramolecular C (sp3) -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 ester-indoline-2-thioketone compound in the synthesis of 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 (sp2) -H and C (sp3) -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 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 the NMR spectra of 3, 3-dicarboxylate-indoline-2-thione compounds synthesized in examples 1 to 26 of the present invention1H NMR、13A C NMR spectrum;
Detailed Description
The present invention will be described in further detail with reference to the following embodiments and the accompanying drawings, and the present invention is not limited to the following 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 (95.2mg, 0.4mmol) were added to a reaction flask, anhydrous acetonitrile 4mL was added, reaction was conducted at 50 ℃ for 1 hour, TLC detection was 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 give pure product 40.4 mg. The structure is shown as formula (2-1). The yield was 72%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 1, and the product:1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)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 C13H13NO4S[M]+279.0565,found 279.0567.
example 2
Figure BDA0002285435600000042
The experimental procedure of this example was substantially the same as in example 1, the starting material used in this example was dimethyl 2- ((4-methoxyphenyl) (methyl) carbamoyl) malonate, and the reaction time was 1 hour at 50 ℃ to obtain the product represented by the formula (2-2). The yield was 77%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 2, and the product:1H NMR(600MHz,CDCl3)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).13C NMR (151MHz,CDCl3)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 C14H15NO5S[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 resonance1H NMR、13The C NMR spectrum is shown in FIG. 3, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151 MHz,CDCl3)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 C14H15NO4S[M]+293.0722,found 293.0720.
example 4
Figure BDA0002285435600000052
This example was conducted in substantially the same manner as in example 1 except that 2- ((4- (N, 4-dimethylphenylsulfonamido) phenyl) (methyl) aminomethylsulfonyl) dimethylmalonate was used as a starting material in this example and reacted at 50 ℃ for 1.5 hours to obtain a product represented by the formula (2-4). The yield was 74%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 4, and the product:1H NMR(600MHz,CDCl3) 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).13C NMR(151MHz,CDCl3)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 C21H22N2O6S2[M]+462.0919,found 462.0915.
example 5
Figure BDA0002285435600000061
This example was conducted in substantially the same manner as in example 1 except that dimethyl 2- ((4-fluorophenyl) (methyl) 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 (2-5). The yield was 69%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 5, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C13H12FNO4S[M]+297.0471,found 297.0469.
example 6
Figure BDA0002285435600000062
The experimental procedure of this example was substantially the same as in example 1, wherein dimethyl 2- ((4-chlorophenyl) (methyl) carbamoyl) malonate was used as the starting material, 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 resonance1H NMR、13The C NMR spectrum is shown in FIG. 6, and the product:1H NMR(600MHz,CDCl3)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).13C NMR (151MHz,CDCl3)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 C13H12ClNO4S[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 resonance1H NMR、13The C NMR spectrum is shown in FIG. 7, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C13H12BrNO4S[M]+356.9670,found 356.9668.
example 8
Figure BDA0002285435600000072
The experimental procedure of this example was substantially the same as in example 1, except that dimethyl 2- ((4-iodophenyl) (methyl) aminomethylcarbamoyl) 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 (2-8). The yield was 42%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 8, and the product:1H NMR(600MHz,CDCl3)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).13C NMR (151MHz,CDCl3)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 C13H12INO4S[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 (70.6mg, 0.2mmol), anhydrous cobalt bromide (4.4mg, 0.02mmol), DBU (76.1mg, 0.5mmol), sodium persulfate (95.2mg, 0.4mmol) and acetonitrile (4mL) 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 resonance1H NMR、13The C NMR spectrum is shown in FIG. 9, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C16H17NO6S[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 (64.6mg, 0.2mmol), anhydrous cobalt bromide (4.4mg, 0.02mmol), DBU (76.1mg, 0.5mmol), sodium persulfate (95.2mg, 0.4mmol) and acetonitrile (4mL) 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 resonance1H NMR、13The C NMR spectrum is shown in FIG. 10, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3) 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 C15H15NO5S[M]+321.0671,found 321.0675.
example 11
Figure BDA0002285435600000091
This example was carried out in substantially the same manner as in example 1, except that dimethyl 2- ((2-methoxyphenyl) (methyl) carbamoyl) malonate (62.2mg, 0.2mmol), anhydrous cobalt bromide (4.4mg, 0.02mmol), DBU (76.1mg, 0.5mmol), persulfuric acidSodium (95.2mg, 0.4mmol) and acetonitrile (4mL) were reacted at 80 ℃ for 2 hours to give the product of formula (2-11). The yield was 61%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 11, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C14H15NO5S[M]+309.0671,found 309.0668.
example 12
Figure BDA0002285435600000092
This example was conducted in substantially the same manner as in example 1 except that dimethyl 2- (methyl (o-tolyl) carbamoyl) malonate (59.0mg, 0.2mmol), anhydrous cobalt bromide (4.4mg, 0.02mmol), DBU (76.1mg, 0.5mmol), sodium persulfate (95.2mg, 0.4mmol) and acetonitrile (4mL) were used as starting materials, and a reaction time of 1 hour at 80 ℃ gave the product represented by the structural formula (2-12). The yield was 69%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 12, and the product:1H NMR(600 MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C14H15NO4S[M]+293.0722,found 293.0723.
example 13
Figure BDA0002285435600000101
The experimental procedure of this example was substantially the same as in example 1, and the starting materials used in this example wereIs dimethyl 2- ((3-methoxyphenyl) (methyl) carbamoyl) malonate, and the reaction time is 1 hour at 50 ℃, and the obtained product is shown as a structural formula (2-13). The yield was 40%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 13, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C14H15NO5S[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 resonance1H NMR、13The C NMR spectrum is shown in FIG. 14, and the product:1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)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 C13H12ClNO4S[M]+313.0176,found 313.0181.
example 15
Figure BDA0002285435600000103
The experimental procedure of this example is essentially the same as in example 1, the starting material used in this example being dimethyl 2- ((3, 5-dimethoxyphenyl) (methyl) aminomethylcarbonyl) malonate, at 50 ℃The reaction time was 1 hour, and the obtained product was represented by the formula (2-15). The yield was 90%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 15, and the product:1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)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 C15H17NO6S[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 resonance1H NMR、13The C NMR spectrum is shown in FIG. 16, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C15H17NO4S[M]+307.0878,found 307.0875.
example 17
Figure BDA0002285435600000112
This example was carried out in essentially the same manner as example 1, using dibenzyl 2- (methyl (phenyl) carbamoyl) malonate as the starting material, reacting at 50 ℃ for 1.5 hours to obtain the product of the same structureThe formula (2-17). The yield was 70%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 17, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz, CDCl3)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 C25H21NO4S[M]+431.1191,found 431.1193.
example 18
Figure BDA0002285435600000121
The experimental procedure of this example was substantially the same as in example 1, except that diisopropyl 2- (methyl (phenyl) 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 (2-18). The yield was 83%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 18, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C17H21NO4S[M]+335.1191,found 335.1189.
example 19
Figure BDA0002285435600000122
The experimental procedure of this example is essentially the same as example 1, the starting material used in this example is dimethyl 2- (isopropyl (phenyl) carbamoyl) malonate, which is reacted at 50 deg.CThe reaction time was 1.5 hours, and the obtained product was represented by the structural formula (2-19). The yield was 78%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 19, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C15H17NO4S[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 resonance1H NMR、13The C NMR spectrum is shown in FIG. 20, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C18H23NO4S[M]+349.1348,found 349.1351.
example 21
Figure BDA0002285435600000132
The experimental procedure of this example is substantially the same as that of example 1, and the experimental procedure used in this exampleThe raw material is 2- ((3-methoxy propyl) (phenyl) carbamoyl) malonic acid dimethyl ester, the reaction time is 1 hour at 50 ℃, and the obtained product is shown as a structural formula (2-21). The yield was 62%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 21, and the product:1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)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 C16H19NO5S[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 resonance1H NMR、13The C NMR spectrum is shown in FIG. 22, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C19H17NO4S[M]+355.0878,found 355.0876.
example 23
Figure BDA0002285435600000142
Experimental method of the present exampleSubstantially the same as in example 1, the starting material used in this example was dimethyl 2- (benzyl (4-methoxyphenyl) aminomonoyl) malonate, and the reaction time was 1 hour at 50 ℃ to obtain the product represented by the formula (2-23). The yield was 68%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 23, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C20H19NO5S[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 resonance1H NMR、13The C NMR spectrum is shown in FIG. 24, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C13H12ClNO4S[M]+313.0176,found 313.0172.
example 25
Figure BDA0002285435600000152
The true bookEXAMPLES Experimental procedures were essentially the same as in example 1, using dimethyl 2- (benzyl (4-bromophenyl) aminomethylcarbonyl) malonate as the starting material, and reacting at 50 ℃ for 2 hours to obtain the product represented by structural formula (2-25). The yield was 46%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 25, and the product:1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)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 C19H16BrNO4S[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) aminomethylcarbonyl) malonate (85.8mg, 0.2mmol), anhydrous cobalt bromide (4.4mg, 0.02mmol), DBU (76.1mg, 0.5mmol), sodium persulfate (95.2mg, 0.4mmol) and acetonitrile (4mL) were used as starting materials, and the reaction time was 2 hours at 80 ℃ to obtain the product represented by the formula (2-26). The yield was 59%. Nuclear magnetic resonance1H NMR、13The C NMR spectrum is shown in FIG. 26, and the product:1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)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 C22H21NO6S[M]+427.1090,found427.1094。

Claims (12)

1. a3, 3-dicarboxylic ester-indoline-2-thioketone compound is characterized by having a structure shown in the following formula (2):
Figure FDA0002285435590000011
wherein,
R1hydrogen, alkyl, ester group, acyl, halogen, alkoxy, sulfonamide;
R2is alkyl, benzyl, substituted alkyl;
R3、R4independently is alkyl or benzyl.
2. A method for synthesizing a 3, 3-dicarboxylate-indoline-2-thione compound, which 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 carry out dehydrogenation coupling reaction of C (sp2) -H and C (sp3) -H in molecules to obtain a 3, 3-dicarboxylic ester-indoline-2-thioketone compound shown in the formula (2); the reaction process is shown as a reaction formula (I):
Figure FDA0002285435590000012
wherein,
R1hydrogen, alkyl, ester group, acyl, halogen, alkoxy, sulfonamide;
R2is alkyl, benzyl, substituted alkyl;
R3、R4independently is alkyl or benzyl.
3. The synthesis method according to claim 2, 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).
4. The synthesis method of claim 2, wherein the oxidant is potassium persulfate, sodium persulfate, DDQ, iodobenzene acetate, copper acetate, DTBP, TBHP, silver oxide, silver carbonate; preferably, sodium persulfate.
5. The synthesis method of claim 2, wherein the catalyst is anhydrous cobalt bromide, anhydrous cobalt chloride, anhydrous cobalt acetate, cobalt (II) acetylacetonate, cobalt (III) tris (2, 4-pentanedionate); preferably, it is anhydrous cobalt bromide.
6. The synthesis method of claim 2, wherein the base is potassium carbonate, potassium phosphate, cesium carbonate, potassium hydroxide, potassium tert-butoxide, triethylamine, DBU, DIPEA; preferably, it is DBU.
7. The synthesis method according to claim 2, 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.
8. The synthesis method according to claim 2, characterized in that the temperature of the reaction is 50 ℃.
9. The synthesis method according to claim 2, wherein the reaction time is 1 to 2 hours.
10. The synthesis method according to claim 2, characterized in that the method further comprises the steps of post-treatment and column chromatographic separation and purification; the separation and purification is to perform column chromatography separation by using an ethyl acetate/petroleum ether mixed solvent as an eluent, wherein the volume ratio of the ethyl acetate to the petroleum ether mixed solvent is 1: 3-1: 10.
11. The synthesis method according to claim 2, characterized in that it comprises in particular: carrying out intramolecular dehydrogenation coupling reaction of C (sp2) -H and C (sp3) -H in an organic solvent at 50-80 ℃ by using N-alkyl/N-aryl thioamide shown in formula (1), an oxidant, a catalyst and a base; TLC monitoring till the raw material reaction is finished, filtering to remove solid, concentrating the filtrate under reduced pressure, and performing column chromatography separation 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).
12. The use of 3, 3-dicarboxylate-indoline-2-thione compounds according to claim 1 for the synthesis of pharmaceutical and optoelectronic materials.
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