CN117865871A - Light and organic co-catalysis synthesis of alpha- (2 or 3-indole) ketone derivative and application thereof - Google Patents

Light and organic co-catalysis synthesis of alpha- (2 or 3-indole) ketone derivative and application thereof Download PDF

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CN117865871A
CN117865871A CN202311497071.2A CN202311497071A CN117865871A CN 117865871 A CN117865871 A CN 117865871A CN 202311497071 A CN202311497071 A CN 202311497071A CN 117865871 A CN117865871 A CN 117865871A
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nmr
chloroform
methyl
indole
hrms
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任世超
聂桂花
刘东汉
涂婷
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Guizhou University
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Guizhou University
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Abstract

The invention discloses a- (2 or 3-indolyl) ketone derivative, which is represented by the following general formula (1):wherein the method comprises the steps of，R 1 Is hydrogen, halogen, methyl or methoxy, R 2 Is alkyl or substituted alkyl, R 3 Is alkyl, aromatic heterocycle or substituted phenyl. The 2 or 3-methylindole and the acyl imidazole disclosed by the invention undergo a free radical coupling reaction to prepare the a- (2 or 3-indolyl) ketone derivative, and the derivative has good universality and good yield which is up to 88%.

Description

Light and organic co-catalysis synthesis of alpha- (2 or 3-indole) ketone derivative and application thereof
Technical Field
The invention relates to a preparation method for synthesizing an alpha- (2 or 3-indole) ketone derivative by catalyzing light and an azacyclo-carbene organic small molecule and a derivatization research.
Background
In recent years, plant fungi and bacteria seriously affect the yield and quality of crops worldwide, and plant fungi diseases directly cause the yield and quality reduction of crops, thereby bringing great economic loss to farmers. For example, gibberella wheat (gibberella zeae. Retch) is a filamentous ascomycete that is a disease that occurs on wheat caused by multiple fusarium infestations. The germ can cause seedling rot, stem basal rot, stem rot and spike rot of wheat, and brings at least 10-20% yield reduction to the country where the wheat is planted each year. Furthermore, phytophthora capsici (Phytophthora capsici) is a pathogenic fungus of the genus Phytophthora subgenera. The germ cyst stems branch irregularly or umbrella, which brings at least a dollar loss of 1 million to the country each year. The pepper anthracnose (Colletotrichum capsicum) can cause pepper rot, which affects the yield of peppers worldwide. In the agricultural production process, plant pathogenic bacteria are made to have a certain resistance to the traditional medicines due to the long-term use of the medicines. Therefore, the creation of a novel efficient, low-toxicity and safe green pesticide has very important significance
Indole skeletons are often found in natural and unnatural compounds, with good biological activity. Various molecules containing indole nucleus have been widely studied in terms of antiviral, antibacterial, antifungal, anticancer, and agricultural chemicals. Therefore, the synthesis of indole compounds has received a great deal of attention. The development of a preparation method of the efficient alpha- (2 or 3-indole) ketone derivative has important application value.
Disclosure of Invention
The invention aims to design and synthesize alpha- (2 or 3-indole) ketone derivatives with novel structures and good substrate universality, and further apply the derivatives to agricultural researches.
The technical scheme of the invention is as follows: an alpha- (2 or 3-indolone derivative represented by the following general formula (1):
wherein R is 1 Is hydrogen, halogen, methyl or methoxy, R 2 Is alkyl or substituted alkyl, R 3 Is alkyl, aromatic heterocycle or substituted phenyl.
Preferably, R 2 Is methyl or CH 2 Ph。
Preferably, the substituent of the substituted phenyl which is benzene ring is halogen, methyl, methoxy, trifluoromethyl or nitro.
Preferably, the halogen is fluorine, chlorine or bromine.
The preparation method of the alpha- (2 or 3-indole) ketone derivatives comprises the following steps:
(1) Substituted methylindole reacts with a photocatalyst to obtain an intermediate I;
(2) Removing protons from the intermediate I to obtain an intermediate II;
(3) The acyl imidazole reacts with the carbene catalyst to obtain an intermediate III, and the intermediate III is reduced by a photocatalyst to obtain an intermediate IV;
(4) And (3) performing free radical coupling on the intermediate II and the intermediate IV to obtain an intermediate V, and finally leaving the carbene to obtain the compound 4.
The reaction general formula and the process are as follows:
the derivatives are used for preventing and controlling agricultural diseases and insect pests.
The agricultural plant diseases and insect pests are plant fungi or bacterial diseases.
The agricultural plant diseases and insect pests are wheat fusarium, potato late blight, blueberry root rot, pepper fusarium, rape sclerotium, rape anthracnose, grape base cavity, rice sheath blight, rice bacterial blight, tobacco bacterial wilt, citrus canker, kiwi fruit canker, cucumber bacterial blight, konjak bacterial blight, grape canker, pepper phytophthora and pepper anthracnose.
The invention has the beneficial effects that: the method comprises the steps of taking common 2-or 3-methylindole and modified carboxylic acid as raw materials, synthesizing a series of a- (2-or 3-indolone derivatives through catalysis of N-heterocyclic carbene (NHC), and then performing a series of derivative synthesis on the synthesized products to obtain indole derivatives with biological activity; it was found to have good universality and good conversion. The indole skeleton synthesized by using the organic micromolecule is a brand new and efficient synthesis method of the indolone compounds, has potential application prospects in the aspects of new pesticide creation and green chiral pesticide creation, and provides a brand new solution and synthesis strategy for the development of new structures on pesticides.
Detailed description of the preferred embodiments
General examples
(1) Synthetic route for the preparation of a- (2 or 3-indolone derivatives):
the preparation implementation method and the conditions are as follows:
0.10mmol of substituted 2 or 3-methylindole 1/2, 0.20mmol of substituted acylimidazole 3, 0.02mmol of azacyclo-carbene catalyst, and 0.001mmol of photocatalyst are respectively weighed into a 10mL Schlenk reaction tube equipped with a magnetic stirrer, 0.05mmol of cesium carbonate (Cs 2 CO 3 ) And 2.0mL of acetonitrile as solvent. The bottle cap is covered, and the mixture is placed in a blue light reactor to be fully stirred for reaction for 12 hours. After the TLC monitoring reaction is finished, separating by column chromatography, obtaining the target compound by eluting with polar petroleum ether of ethyl acetate=30:1, weighing, calculating the corresponding yield, and characterizing the compound by a melting point instrument, a polarimeter, a nuclear magnetic resonance spectrometer NMR and a high resolution mass spectrometer HRMS.
(2) Derivatization studies on the synthesized a- (2 or 3-indolone derivatives:
the target compound was obtained, the corresponding yield was calculated after weighing, and the compound was characterized by a melting point apparatus, polarimeter, nuclear magnetic resonance NMR, high resolution mass spectrometer HRMS.
Process for the preparation by conversion of compounds
Process for the preparation of compound 5h to compound 9
A10.0 mL clean bottle equipped with a magnetic stirrer was charged with 37.45mg of 5h in 1.0mL dibutyl ether and 13 μLTfOH was added for 4 hours at room temperature. After the TLC monitoring, the reaction was quenched by adding sodium bicarbonate, extracted three times with ethyl acetate, dried, spun-dried, and separated by column chromatography, eluting with polar petroleum ether, ethyl acetate=20:1 to give the target compound 9 in 75% yield.
Process for the preparation of compound 5h to compound 10
A10.0 mL clean bottle equipped with a magnetic stirrer was charged with 37.45mg of 5h in 1.0mL of toluene and reacted for 24 hours at room temperature with 40. Mu.LMsOH. After the TLC monitoring reaction was completed, the reaction was quenched by adding sodium bicarbonate, extracted three times with ethyl acetate, dried, spun-dried, and separated by column chromatography, eluting with polar petroleum ether, ethyl acetate=20:1 to yield the target compound 10, 36%.
Process for the preparation of compound 4u to compound 11
A10.0 mL clean bottle equipped with a magnetic stirrer was charged with 37.45mg of 4u in 1.0mL of toluene, and 7mg of D-CSA was added thereto and reacted at room temperature for 60 hours at 60 ℃. After the TLC monitoring, the reaction was quenched by adding sodium bicarbonate, extracted three times with ethyl acetate, dried, spun-dried, and separated by column chromatography, eluting with polar petroleum ether, ethyl acetate=20:1 to give the target compound 11 in 59% yield.
Process for the preparation of compound 4a to compound 12
A10.0 mL clean bottle equipped with a magnetic stirrer was charged with 37.45mg of 4u in 1.0mL of toluene, and 14mg of D-CSA was added thereto and reacted at room temperature for 24 hours at 60 ℃. After the TLC monitoring reaction was completed, the reaction was quenched by adding sodium bicarbonate, extracted three times with ethyl acetate, dried, spun-dried, and separated by column chromatography, eluting with polar petroleum ether, ethyl acetate=20:1 to yield the target compound 12, 64% yield.
The synthetic compounds were experimentally characterized as follows: 1- (4-methoxyphenyl) -2- (1-methyl-1H-2-indol) one (4 a)
Yield; 21mg; melting point: 175-177 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.06–8.03(m,2H),7.55–7.52(m,1H),7.30–7.28(m,1H),7.21–7.16(m,1H),7.09–7.05(m,1H),6.95–6.92(m,2H),6.36(d,J＝0.8Hz,1H),4.41(s,2H),3.87(s,3H),3.69(s,3H).
13 C NMR(101MHz,Chloroform-d)δ194.4,163.8,137.7,133.8,131.0,129.3,127.7,121.2,120.1,119.4,113.9,109.1,102.0,55.5,37.6,30.0.
HRMS(ESI-TOF,m/z):Mass calcd.for C 18 H 17 NO 2 + [M+Na] + ,302.1152；found:302.1149.
1- (4-tert-butylphenyl) -2- (1-methyl-1H-2-indole) (4 c)
Yield; 27mg; melting point: 158-160 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.03–8.00(m,2H),7.57–7.49(m,3H),7.30(dd,J＝8.2,1.0Hz,1H),7.22–7.18(m,1H),7.11–7.07(m,1H),6.40(s,1H),4.45(s,2H),3.70(s,3H),1.36(s,9H).
13 C NMR(101MHz,Chloroform-d)δ195.4,157.3,137.7,133.6,133.6,128.6,127.7,125.7,121.2,120.1,119.4,109.1,102.0,37.7,35.2,31.0,30.0.
HRMS(ESI-TOF,m/z):Mass calcd.for C 21 H 23 NONa + [M+Na] + ,328.1672；found:328.1673.
1- (4-chlorophenyl) -2- (1-methyl-1H-2-indole) (4 d)
A rate; 21mg; melting point: 160-162 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.01–7.97(m,2H),7.54(dt,J＝7.8,1.1Hz,1H),7.11–7.07(m,1H),6.37–7.36(m,1H),4.43(d,J＝0.8Hz,2H),3.69(s,3H).
13 C NMR(101MHz,Chloroform-d)δ194.7,140.0,137.7,134.4,132.8,130.0,129.1,127.6,121.4,120.2,119.6,109.1,102.2,37.9,30.0.
HRMS(ESI-TOF,m/z):Mass calcd.for C 17 H 14 ClNONa + [M+Na] + ,306.0656；found:306.0655.
1- (4-fluorophenyl) -2- (1-methyl-1H-2-indole) (4 e)
23mg; melting point: 165-167 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.11–8.06(m,2H),7.56–7.53(m,1H),7.30(dd,J＝8.2,1.0Hz,1H),7.22–7.12(m,3H),7.11–7.07(m,1H),6.38(s,1H),4.43(s,2H),3.69(s,3H).
13 C NMR(101MHz,Chloroform-d)δ194.3,166.0(d,J＝256.0Hz),137.8,133.0,132.6(d,J＝4.0Hz),131.3(d,J＝9.4Hz),127.7,121.4,120.2,119.6,115.9(d,J＝21.9Hz),109.1,102.2,37.8,30.0.
19 F NMR(377MHz,Chloroform-d)δ-104.24.
HRMS(ESI-TOF,m/z):Mass calcd.for C 17 H 14 FNONa + [M+Na] + ,290.0952；found:290.0952.
1- (4-trifluoromethylphenyl) -2- (1-methyl-1H-2-indole) (4 f)
Yield; 24.7mg; melting point: 194-196 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.17–8.14(m,2H),7.75(d,J＝8.2Hz,2H),7.55(dt,J＝7.8,1.0Hz,1H),7.31(dd,J＝8.2,1.0Hz,1H),7.23–7.19(m,1H),7.11–7.07(m,1H),6.38(s,1H),4.48(s,2H),3.70(s,3H).
13 C NMR(101MHz,Chloroform-d)δ194.9,138.8,137.8,134.8(q,J＝32.7Hz),132.4,129.0,127.6,125.8(q,J＝3.7Hz),123.5(d,J＝273.1Hz),121.5,120.3,119.7,109.2,102.4,38.1,30.0.
19 F NMR(377MHz,Chloroform-d)δ-63.18.
HRMS(ESI-TOF,m/z):Mass calcd.for C 18 H 14 F 3 NONa + [M+Na] + ,340.0920；found:340.0918.
2- (1-methyl-1H-2-indol) -1-phenyl-one (4H)
Melting point: 121-123 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.08–8.05(m,2H),7.62–7.47(m,4H),7.31(dd,J＝8.4,1.0Hz,1H),7.22–7.18(m,1H),7.11–7.07(m,1H),6.39(s,1H),4.47(s,2H),3.70(s,3H).
13 C NMR(101MHz,Chloroform-d)δ195.8,137.8,136.2,133.5,133.3,128.7,128.6,127.7,121.2,120.2,119.5,109.1,102.1,37.7,30.0.
HRMS(ESI-TOF,m/z):Mass calcd.for C 17 H 15 NONa + [M+Na] + ,272.1046；found:272.1049.
1- (3-methoxyphenyl) -2- (1-methyl-1H-2-indole) (4 i)
A rate; 24mg; melting point: 156-158 ℃.
1 H NMR(400MHz,Chloroform-d)δ7.66(dt,J＝7.8,1.2Hz,1H),7.58–7.54(m,2H),7.40(t,J＝8.0Hz,1H),7.30(dd,J＝8.2,1.0Hz,1H),7.22–7.18(m,1H),7.16–7.07(m,2H),6.39(s,1H),4.45(s,2H),3.86(s,3H),3.69(s,3H).
13 C NMR(101MHz,Chloroform-d)δ195.7,159.9,137.8,137.6,133.3,129.7,127.7,121.2,121.2,120.2,112.0,119.5,112.9,109.1,102.1,55.4,37.8,30.0.
HRMS(ESI-TOF,m/z):Mass calcd.for C 18 H 17 NO 2 Na + [M+Na] + ,302.1152；found:302.1153.
1- (3-chlorophenyl) -2- (1-methyl-1H-2-indole) (4 k)
24.1mg; melting point: 176-178 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.02(t,J＝1.8Hz,1H),7.93(dt,J＝7.8,1.4Hz,1H),7.57–7.53(m,2H),7.43(t,J＝8.0Hz,1H),7.33–7.28(m,1H),7.22–7.18(m,1H),7.10–7.06(m,1H),6.38(s,1H),4.44(s,2H),3.68(s,3H).
13 C NMR(101MHz,Chloroform-d)δ194.6,137.8,137.7,135.2,133.4,132.6,130.1,128.7,127.6,126.7,121.4,120.3,119.6,109.1,102.3,37.8,30.0.
HRMS(ESI-TOF,m/z):Mass calcd.for C 17 H 14 ClNONa + [M+Na] + ,306.0656；found:306.0657.
1- (3-fluorophenyl) -2- (1-methyl-1H-2-indole) (4 l)
22.3mg; melting point: 149-151 ℃.
1 H NMR(400MHz,Chloroform-d)δ7.85(dt,J＝7.8,1.2Hz,1H),7.75–7.72(m,1H),7.55(dt,J＝7.8,1.2Hz,1H),7.50–7.44(m,1H),7.32–7.27(m,2H),7.18–7.12(m,1H),7.11–7.07(m,1H),6.39(s,1H),4.44(s,2H),3.69(s,3H).
13 C NMR(101MHz,Chloroform-d)δ194.6(d,J＝2.7Hz),162.9(d,J＝248.5Hz),138.3(d,J＝6.5Hz),137.8,132.7,130.5(d,J＝7.9Hz),127.7,124.4(d,J＝2.9Hz),121.4,120.6(d,J＝21.4Hz),120.3,119.6,115.4(d,J＝22.4Hz),109.2,102.3,37.9,30.0.
19 F NMR(377MHz,Chloroform-d)δ-111.34.
HRMS(ESI-TOF,m/z):Mass calcd.for C 17 H 14 FNONa + [M+Na] + ,290.0952；found:290.0951.
1- (3-Methylesterphenyl) -2- (1-methyl-1H-2-indole) (4 m)
A rate; 21.4mg; melting point: 182-184 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.72(t,J＝1.8Hz,1H),8.27–8.22(m,2H),7.60–7.53(m,2H),7.30(dd,J＝8.2,1.0Hz,1H),7.22–7.18(m,1H),7.10–7.06(m,1H),6.40(s,1H),4.51(s,2H),3.97(s,3H),3.70(s,3H).
13 C NMR(101MHz,Chloroform-d)δ195.0,166.1,137.8,136.4,134.2,132.77,132.7,130.9,129.7,129.1,127.7,121.4,120.2,119.5,109.1,102.3,52.4,37.8,30.0.
HRMS(ESI-TOF,m/z):Mass calcd.for C 19 H 17 NO 3 Na + [M+Na] + ,330.1100；found:330.1103.
1- (2-chlorophenyl) -2- (1-methyl-1H-2-indole) (4 o)
12.7mg; melting point: 168-170 ℃.
1 H NMR(400MHz,Chloroform-d)δ7.54(d,J＝7.8Hz,1H),7.47–7.37(m,3H),7.32–7.28(m,2H),7.22–7.18(m,1H),7.10–7.06(m,1H),6.37(s,1H),4.47(s,2H),3.70(s,3H).
13 C NMR(101MHz,Chloroform-d)δ198.9,138.66,137.8,132.3,132.0,130.9,130.6,129.3,127.7,127.0,121.4,120.3,119.5,109.2,102.4,41.6,30.0.
HRMS(ESI-TOF,m/z):Mass calcd.for C 17 H 14 ClNONa + [M+Na] + ,306.0656；found:306.0657.
2- (1-methyl-1H-2-indol) -1- (naphtyl) one (4 p)
17.3mg; melting point: 163-165 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.62–8.61(m,1H),8.09(dd,J＝8.6,1.8Hz,1H),8.00–7.98(m,1H),7.93–7.88(m,2H),7.65–7.53(m,3H),7.31(dd,J＝8.4,1.0Hz,1H),7.22–7.18(m,1H),7.10–7.06(m,1H),6.43(d,J＝0.8Hz,1H),4.61(s,2H),3.73(s,3H).
13 C NMR(101MHz,Chloroform-d)δ195.8,137.8,135.8,133.6,133.4,132.5,130.4,129.7,128.8 128.7,127.8,127.7,126.3,124.1,121.3,120.2,119.5,109.1,102.2,37.8,30.1.
HRMS(ESI-TOF,m/z):Mass calcd.for C 21 H 17 NONa + [M+Na] + ,322.1202；found:322.11199.
2- (1-methyl-1H-2-indol) -1- (3-pyridine) one (4 r)
20.7mg; melting point: 127-129 ℃.
1 H NMR(400MHz,Chloroform-d)δ9.29(dd,J＝2.4,0.8Hz,1H),8.79(dd,J＝4.8,1.8Hz,1H),8.30(dt,J＝8.0,2.0Hz,1H),7.54(dt,J＝8.0,1.0Hz,1H),7.45–7.41(m 1H),7.31–7.29(m,1H),7.22–7.18(m,1H),7.11–7.07(m,1H),6.40(s,1H),4.47(s,2H),3.70(s,3H).
13 C NMR(101MHz,Chloroform-d)δ194.7,153.8,150.0,137.8,135.9,132.1,131.4,127.6,123.8,121.5,120.3,119.6,109.2,102.4,38.0,30.0.
HRMS(ESI-TOF,m/z):Mass calcd.for C 16 H 15 N 2 O + [M+H] + ,251.1179；found:251.1181.
2- (1-methyl-1H-2-indol) -1- (2-thiophene) one (4 s)
16.8mg; melting point: 99-101 ℃.
1 H NMR(400MHz,Chloroform-d)δ7.83(dd,J＝3.8,1.2Hz,1H),7.66(dd,J＝5.0,1.2Hz,1H),7.56(dt,J＝8.0,1.0Hz,1H),7.31–7.28(m,1H),7.22–7.18(m,1H),7.13(dd,J＝5.0,3.8Hz,1H),7.11–7.07(m,1H),6.44(d,J＝0.9Hz,1H),4.39(s,1H),4.39(s,2H),3.72(s,3H).
13 C NMR(101MHz,Chloroform-d)δ188.6,143.2,137.8,134.3,133,132.9,128.3,127.6,121.4,120.2,119.6,109.2,102.3,38.8,30.1.
HRMS(ESI-TOF,m/z):Mass calcd.for C 15 H 13 NOSNa + [M+Na] + ,278.0610；found:278.0613.
1- (furan-2-yl) -2- (1-methyl-1H-2-indol) one (4 t)
15.6mg; melting point: 102-104 ℃.
1 H NMR(400MHz,Chloroform-d)δ7.61(dd,J＝1.8,0.8Hz,1H),7.54(dt,J＝8.0,1.0Hz,1H),7.29(dd,J＝8.2,1.0Hz,1H),7.25–7.24(m,1H),7.21–7.17(m,1H),7.10–7.06(m,1H),6.54(dd,J＝3.6,1.8Hz,1H),6.43(q,J＝0.8Hz,1H),4.32(d,J＝0.7Hz,2H),3.72(s,3H).
13 C NMR(101MHz,Chloroform-d)δ184.6,152.0,146.7,137.8,132.7,127.7,121.3,120.2,119.5,118.2,112.6,109.2,102.2,37.5,30.1.
HRMS(ESI-TOF,m/z):Mass calcd.for C 15 H 13 NO 2 Na + [M+Na] + ,262.0839；found:262.0841.
1- (1-methyl-1H-2-indol-2-yl) acetone (4 u)
1 H NMR(400MHz,Chloroform-d)δ7.58(dt,J＝8.0,1.0Hz,1H),7.31–7.28(m,1H),7.23–7.19(m,1H),7.13–7.09(m,1H),6.41(d,J＝0.8Hz,1H),3.87(s,2H),3.65(s,3H),2.20(s,3H).
13 C NMR(101MHz,Chloroform-d)δ205.0,137.8,133.0,127.7,121.5,120.2,119.7,109.2,102.0,42.9,29.8,28.9.
HRMS(ESI-TOF,m/z):Mass calcd.for C 12 H 14 NO + [M+H] + ,188.1070；found:188.1073.
2- (6-methoxy-1-methyl-1H-2-indol) -1- (4-methoxyphenyl) one (4 ad)
Example I; white solid, 49% yield; 15mg; melting point: 161-162 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.06–8.02(m,2H),7.41–7.39(m,1H),6.96–6.93(m,2H),6.75(d,J＝7.8Hz,2H),6.29(d,J＝0.8Hz,1H),4.37(d,J＝0.8Hz,2H),3.87(s,6H),3.64(s,3H).
13 C NMR(101MHz,Chloroform-d)δ194.6,163.8,156.0,138.4,132.6,130.9,129.3,122.0,120.7,113.9,109.1,101.8,93.1,55.8,55.5,37.6,30.1.
HRMS(ESI-TOF,m/z):Mass calcd.for C 19 H 19 NO 3 Na + [M+Na] + ,332.1257；found:332.1257.
2-methoxy-1- (4-methoxybenzene) -2- (1-methyl-1H-2-indol) one (4 ak)
Yield; 20.5mg; melting point: 123-125 ℃.
1 H NMR(400MHz,Chloroform-d)δ8.07–8.03(m,2H),7.55(dt,J＝8.0,1.0Hz,1H),7.32–7.30(m,1H),7.25–7.20(m,1H),7.10–7.06(m,1H),6.89–6.86(m,2H),6.53(s,1H),5.77(s,1H),3.83(s,3H),3.80(s,3H),3.48(s,3H).
13 C NMR(101MHz,Chloroform-d)δ193.8,163.8,138.4,134.1,131.4,128.0,127.1,122.3,120.9,119.7,113.7,109.3,104.5,80.1,57.1,55.4,30.4.
HRMS(ESI-TOF,m/z):Mass calcd.for C 19 H 19 NO 3 + [M+Na] + ,332.1257；found:332.1257.
1- (4-tert-butylphenyl) -2- (1-methyl-1H-3-indol) one (5 b)
21mg。
1 H NMR(400MHz,Chloroform-d)δ8.02–7.99(m,2H),7.62(dt,J＝7.8,1.0Hz,1H),7.47–7.45(m,2H),7.30(dt,J＝8.2,1.0Hz,1H),7.26–7.21(m,1H),7.16–7.12(m,1H),7.01(d,J＝1.0Hz,1H),4.38(d,J＝1.0Hz,2H),3.74(s,3H),1.33(s,9H).
13 C NMR(101MHz,Chloroform-d)δ197.5,156.7,136.9,134.1,128.6,127.8,125.5,121.7,119.2,118.9,109.3,107.5,35.31,35.07,32.69,31.06.
HRMS(ESI-TOF,m/z):Mass calcd.for C 21 H 23 NONa + [M+Na] + ,328.1672；found:328.1664.
1- (4- (allyloxy) phenyl) -2- (1-methyl-1H-3-indol) one (5 c)
1 H NMR(400MHz,Chloroform-d)δ8.05–8.01(m,2H),7.61(dt,J＝7.8,1.0Hz,1H),7.29(dt,J＝8.2,1.0Hz,1H),7.25–7.21(m,1H),7.15–7.11(m,1H),6.98(d,J＝1.0Hz,1H),6.94–6.90(m,2H),6.09–5.99(m,1H),5.57–5.25(m,2H),5.42(dq,J＝17.4,1.6Hz,1H),5.31(dq,J＝10.6,1.4Hz,1H),4.34(d,J＝0.4Hz,2H),3.74(s,3H).
13 C NMR(101MHz,Chloroform-d)δ196.6,162.4,136.9,132.5,130.9,129.9,127.8,127.7,121.7,119.1,118.9,118.1,114.4,109.2,107.6,68.9,35.2,32.7.
HRMS(ESI-TOF,m/z):Mass calcd.for C 20 H 19 NO 2 Na + [M+Na] + ,328.1308；found:328.1309.
1- (4-Acetylbenzene) -2- (1-methyl-1H-3-indol) one (5 d)
1 H NMR(400MHz,Chloroform-d)δ8.13–8.10(m,2H),8.01–7.98(m,2H),7.60(dt,J＝8.0,1.0Hz,1H),7.30(dt,J＝8.2,1.0Hz,1H),7.26–7.22(m,1H),7.16–7.12(m,1H),6.99(d,J＝1.0Hz,1H),4.42(d,J＝1.0Hz,2H),3.74(s,3H),2.62(s,3H).
13 C NMR(101MHz,Chloroform-d)δ197.5,197.3,140.1,139.9,137.0,128.8,128.5,127.9,127.6,121.9,119.4,118.7,109.4,106.7,35.9,32.7,26.8.
HRMS(ESI-TOF,m/z):Mass calcd.for C 19 H 17 NO 2 Na + [M+Na] + ,314.1152；found:314.1150.
1- (3-Methylesterphenyl) -2- (1-methyl-1H-3-indol) one (5 e)
A rate; 20.3mg.
1 H NMR(400MHz,Chloroform-d)δ8.74(t,J＝1.8Hz,1H),8.24–8.19(m,2H),7.63(dt,J＝7.8,1.0Hz,1H),7.52(td,J＝7.8,0.6Hz,1H),7.30(dt,J＝8.4,1.0Hz,1H),7.26–7.22(m,1H),7.16–7.12(m,1H),7.02(d,J＝1.0Hz,1H),4.44(d,J＝1.0Hz,2H),3.95(s,3H),3.74(s,3H).
13 C NMR(101MHz,Chloroform-d)δ196.9,166.3,136.9,136.8,133.7,132.7,130.6,129.7,128.8,127.9,127.7,121.8,119.2,118.8,109.3,106.7,52.3,35.6,32.7.
HRMS(ESI-TOF,m/z):Mass calcd.for C 19 H 17 NO 3 Na + [M+Na] + ,330.1100；found:330.1102.
2- (1-methyl-1H-3-indol) -1- (2-Neyl-) one (5 f)
1 H NMR(400MHz,Chloroform-d)δ8.62–8.61(m,1H),8.10(dd,J＝8.6,1.8Hz,1H),7.96–7.93(m,1H),7.89–7.85(m,2H),7.67(dt,J＝7.8,1.0Hz,1H),7.61–7.57(m,1H),7.56–7.52(m,1H),7.30(dt,J＝8.2,1.0Hz,1H),7.26–7.22(m,1H),7.18–7.14(m,1H),7.03(d,J＝1.0Hz,1H),4.53(d,J＝1.0Hz,2H),3.74(s,3H).
13 C NMR(101MHz,Chloroform-d)δ197.9,137.0,135.6,134.1,132.6,130.3,129.6,128.4,127.85,127.8,127.7,126.7,124.4,121.8,119.2,118.9,109.3,107.4,35.5,32.7.
HRMS(ESI-TOF,m/z):Mass calcd.for C 21 H 17 NONa + [M+Na] + ,322.1202；found:322.1203.
1- (1-methyl-1H indol-3-yl) 2-propanone (5H)
1 H NMR(400MHz,Chloroform-d)δ7.53(dt,J＝8.0,1.0Hz,1H),7.32(dt,J＝8.2,1.0Hz,1H),7.26–7.22(m,1H),7.15–7.11(m,1H),7.00(d,J＝1.0Hz,1H),3.81(s,2H),3.78(s,3H),2.17(s,3H).
13 C NMR(101MHz,Chloroform-d)δ207.5,137.0,127.8,127.7,121.9,119.3,119.3,118.8,109.3,107.1,40.7,32.7,28.9.
HRMS(ESI-TOF,m/z):Mass calcd.for C 12 H 13 NONa + [M+Na] + ,210.0889；found:210.0894.
2- (1-benzyl-1H-3-indol) -1- (4-methoxyphenyl) one (5 n)
1 H NMR(400MHz,Chloroform-d)δ8.06–8.00(m,2H),7.65–7.63(m,1H),7.29–7.23(m,4H),7.19–7.13(m,2H),7.11–7.06(m,3H),6.94–6.89(m,2H),5.27(s,2H),4.36(d,J＝1.0Hz,2H),3.85(s,3H).
13 C NMR(101MHz,Chloroform-d)δ196.5,163.4,137.5,136.6,130.9,130.4,129.8,128.7,128.1,127.5,127.2,126.8,121.9,119.4,119.0,114.1,113.7,109.8,108.5,55.42,49.99,35.32.
HRMS(ESI-TOF,m/z):Mass calcd.for C 24 H 21 NO 2 Na + [M+Na] + ,378.1455；found:378.1453.
2- (3-ethyl-1-methyl-1H-2-indol-) -1- (4-methylbenzene) one (7 e)
Yield, 16.1mg.
1 H NMR(400MHz,Chloroform-d)δ8.07–8.02(m,2H),7.58(dt,J＝8.0,1.0Hz,1H),7.29–7.25(m,2H),7.20–7.16(m,1H),7.10–7.06(m,1H),6.99–6.95(m,2H),4.41(s,2H),3.89(s,3H),3.62(s,3H),2.76(q,J＝7.6Hz,2H),1.20(t,J＝7.6Hz,3H).
13 C NMR(101MHz,Chloroform-d)δ194.6,163.8,137.2,130.7,129.6,129.3,127.2,121.1,118.6,118.6,115.5,113.9,108.9,55.5,34.9,30.0,17.9,15.8.
HRMS(ESI-TOF,m/z):Mass calcd.for C 20 H 21 NO 2 Na + [M+Na] + ,330.1465；found:330.1464.
3- (4-Isobutylbenzene) -1- (1-methyl-1H-2-indole) 2-butanone (8 e)
1 H NMR(400MHz,Chloroform-d)δ7.56(dt,J＝7.8,1.0Hz,1H),7.24–7.17(m,2H),7.13–7.05(m,5H),6.29(s,1H),3.95(q,J＝7.0Hz,1H),3.87–3.77(m,2H),3.39(s,3H),2.47(d,J＝7.2Hz,2H),1.87(dt,J＝13.6,6.8Hz,1H),1.39(d,J＝7.0Hz,3H),0.93(dd,J＝6.6,1.4Hz,6H).
13 C NMR(101MHz,Chloroform-d)δ207.0,140.9,137.6,137.2,133.1,129.7,127.7,127.7,121.2,120.1,119.5,109.1,102.0,51.1,45.0,40.1,30.2,29.5,22.4,22.3,17.5.
HRMS(ESI-TOF,m/z):Mass calcd.for C 23 H 27 NONa + [M+Na] + ,356.1985；found:356.1981.
3- (4-isobutylbenzene) -1- (1-methyl-1H-3-indole) 2-butanone (8 f)
1 H NMR(400MHz,Chloroform-d)δ7.31(dt,J＝7.8,1.0Hz,1H),7.28(dt,J＝8.2,1.0Hz,1H),7.22–7.18(m,1H),7.11(s,4H),7.09–7.02(m,1H),6.86(s,1H),3.90(q,J＝6.8Hz,1H),3.80–3.69(m,5H),2.47(d,J＝7.2Hz,2H),1.87(dt,J＝13.6,6.8Hz,1H),1.34(d,J＝6.8Hz,3H),0.92(d,J＝6.6Hz,6H).
13 C NMR(101MHz,Chloroform-d)δ209.0,140.6,138.0,136.8,129.6,128.0,127.8,127.7,121.7,119.1,118.8,109.2,107.1,51.1,45.0,37.7,32.7,30.2,22.4,17.8.
HRMS(ESI-TOF,m/z):Mass calcd.for C 23 H 27 NONa + [M+Na] + ,356.1985；found:356.1984.
3- (2-fluoro- [1,1' -4-biphenyl) -1- (1-methyl-1H-3-indole) 2-butanone (8H)
1 H NMR(400MHz,Chloroform-d)δ7.55–7.53(m,2H),7.47–7.43(m,2H),7.40–7.35(m,3H),7.30(dt,J＝8.4,1.0Hz,1H),7.25–7.21(m,1H),7.12–7.07(m,1H),7.02(dd,J＝8.0,1.8Hz,1H),6.96(dd,J＝11.6,1.8Hz,1H),6.91(s,1H),3.97(q,J＝7.0Hz,1H),3.89–3.77(m,2H),3.76(s,3H),1.39(d,J＝7.0Hz,3H).
13 C NMR(101MHz,Chloroform-d)δ208.2,159.8(d,J＝248.8Hz),142.1(d,J＝7.4Hz),136.9,135.4,131.0(d,J＝4.2Hz),128.9(d,J＝2.9Hz),128.5,128.0,127.8,127.7,123.9(d,J＝3.6Hz),121.8,119.3,118.7,115.6(d,J＝23.3Hz),109.3,106.7,50.6,38.3,32.7,17.9.
19 F NMR(377MHz,Chloroform-d)δ-117.39.
HRMS(ESI-TOF,m/z):Mass calcd.for C 25 H 22 FNONa + [M+Na] + ,394.1578；found:394.1572.
5,6,12, 13-tetramethyl-6, 13-cyclooctyl [1,2-b:5,6-b' ] diindole (9)
(m,2H),7.03–6.99(m,2H),3.78(s,6H),3.22–3.10(m,4H),1.91(s,6H).
13 C NMR(101MHz,Chloroform-d)δ137.7,137.5,126.1,121.2,118.9,117.7,108.8,107.0,72.1,34.1,31.3,27.0.
HRMS(ESI-TOF,m/z):Mass calcd.for C 24 H 24 N 2 ONa + [M+Na] + ,379.1781；found:379.1775.
1,3, 9-trimethyl-2- (1-methyl-1H-3-indole) -9H-carbazole (10)
7.29–7.19(m,3H),7.10–7.06(m,1H),6.95(s,1H),4.12(s,3H),3.90(s,3H),2.58(s,3H),2.21(s,3H).
13 C NMR(101MHz,Chloroform-d)δ142.5,139.1,136.8,132.9,129.8,128.3,127.6,125.3,122.9,122.7,121.5,121.1,120.2,119.8,119.1,118.7,118.1,115.2,109.1,108.6,33.0,32.8,21.7,17.4.
HRMS(ESI-TOF,m/z):Mass calcd.for C 24 H 23 N 2 + [M+H] + ,339.1856；found:339.1850.
5,7,12,14-tetramethyl-7, 14-cyclooctyl [1,2-b:5,6-b' ] diindole (11)
6H),3.15–3.01(m,4H),1.99(s,6H).
13 C NMR(101MHz,Chloroform-d)δ137.0,134.4,123.9,120.2,118.8,118.3,112.6,109.0,72.2,34.7,29.0,28.2.
HRMS(ESI-TOF,m/z):Mass calcd.for C 24 H 24 N 2 ONa + [M+Na] + ,379.1781；found:379.1775.
(6Z, 13Z) -7, 14-bis (4-methoxybenzene) -5, 12-dimethyl-5, 12-cyclooctene [1,2-b:5,6-b' ] diindole (12)
(m,4H),7.20(dt,J＝8.2,0.8Hz,2H),7.10–7.05(m,2H),6.85–6.80(m,8H),6.70(dt,J＝7.8,1.0Hz,2H),3.82(s,6H),3.75(s,6H).
13 C NMR(101MHz,Chloroform-d)δ159.6,144.7,138.1,138.1,134.3,129.1,127.2,121.3,120.5,119.1,117.0,113.9,113.6,108.9,55.3,29.9.
HRMS(ESI-TOF,m/z):Mass calcd.for C 36 H 30 N 2 O 2 Na + [M+Na] + ,545.2199；found:545.2194.
2, 6-4 methylpiperidin-1-yl 4-p-methoxybenzoic acid methyl ester (13)
2H),6.96–6.93(m,2H),3.87(s,3H),1.82–1.63(m,3H),1.60–1.56(m,2H),1.48–1.42(m,1H),1.26(s,6H),1.11(s,6H).
13 C NMR(101MHz,Chloroform-d)δ166.0,163.2,131.4,121.9,113.6,60.2,55.3,38.9,31.8,20.7,16.9.
Pharmacological example 1 application of alpha- (2 or 3-indolyl) ketone derivative to pathogenic fungi resistance the obtained compounds were tested for bacteriostatic activity against phytophthora capsici (p.capsici), gibberella wheat (g.zeae (schw.) Petch), sclerotinia sclerotiorum (s.sclerotiorum) and aspergillus flavus (a.flavus) plant pathogens. The test results show that the target part of the compound has a certain inhibitory activity on the germs at the concentration of 50 mug/mL. For phytophthora capsici (P.capsici), the compounds with better activity comprise 4d,4p,4r,4u and 5b, and the inhibition rate reaches 40-50%. For sclerotinia sclerotiorum (S.sclerotiorum), the compounds have 4u,4ak,4n and 7e, and the inhibition rate reaches 40-60%. Is superior to the control medicine Azoxystrobin (37%). For Aspergillus flavus (A.flavus), the compounds include compounds such as 4e,4m,4p,4u,5c,5e,5n, 8h and the like, and the inhibition rate reaches 40-52%. Is superior to the control Azoxystrobin (34%). For the wheat gibberella (G.zeae (Schw.) Petch), the compounds have compounds of 4h,4i,4k, 4o and the like, and the inhibition rate reaches 50-64%. Is superior to the control medicine Azoxystrobin (41%).
Table one: inhibition rate of target compound alpha- (2 or 3-indolone derivative on plant fungal disease
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Claims (10)

1. A class of a- (2 or 3-indole) ketone derivatives is characterized in that: the derivative is represented by the following general formula (1):
wherein R is 1 Is hydrogen, halogen, methyl or methoxy, R 2 Is alkyl or substituted alkyl, R 3 Is alkyl, aromatic heterocycle or substituted phenyl.
2. A class of a- (2 or 3-indolone derivatives according to claim 1, characterized in that: r is R 2 Is methyl or CH 2 Ph。
3. A class of a- (2 or 3-indolone derivatives according to claim 1, characterized in that: the substituent of the substituted phenyl which is a benzene ring is halogen, methyl, methoxy, trifluoromethyl or nitro.
4. A- (2 or 3-indolone derivative according to claim 1 or 3, characterized in that: the halogen is fluorine, chlorine or bromine.
5. A class of a- (2 or 3-indolone derivatives according to claim 1, characterized in that: the aromatic heterocycle is quinoline, pyridine, thiophene and furan.
6. A process for the preparation of the a- (2 or 3-indolone derivatives as claimed in claim 1, wherein: the method comprises the following steps:
(1) Substituted methylindole reacts with a photocatalyst to obtain an intermediate I;
(2) Removing protons from the intermediate I to obtain an intermediate II;
(3) The acyl imidazole reacts with the carbene catalyst to obtain an intermediate III, and the intermediate III is reduced by a photocatalyst to obtain an intermediate IV;
(4) The intermediate II and the intermediate IV are subjected to free radical coupling to obtain an intermediate V, and finally the compound 4 is obtained after the carbene leaves;
the reaction general formula and the process are as follows:
7. use of the derivatives according to any one of claims 1 to 5 for controlling agricultural pests.
8. Use according to claim 7, characterized in that: the agricultural plant diseases and insect pests are plant fungi or bacterial diseases.
9. Use according to claim 8, characterized in that: the agricultural plant diseases and insect pests are phytophthora infestans, botrytis cinerea, aspergillus flavus and sclerotinia rot of rape.
10. Use according to claim 8, characterized in that: the agricultural plant diseases and insect pests are wheat fusarium, potato late blight, blueberry root rot, pepper fusarium, rape sclerotium, rape anthracnose, grape base cavity, rice sheath blight, rice bacterial blight, tobacco bacterial wilt, citrus canker, kiwi fruit canker, cucumber bacterial blight, konjak bacterial blight, grape canker, pepper phytophthora and pepper anthracnose.
CN202311497071.2A 2023-11-10 2023-11-10 Light and organic co-catalysis synthesis of alpha- (2 or 3-indole) ketone derivative and application thereof Pending CN117865871A (en)

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