CN107162954B - A kind of synthetic method of indole-2-ketone class compound - Google Patents

A kind of synthetic method of indole-2-ketone class compound Download PDF

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CN107162954B
CN107162954B CN201710607677.5A CN201710607677A CN107162954B CN 107162954 B CN107162954 B CN 107162954B CN 201710607677 A CN201710607677 A CN 201710607677A CN 107162954 B CN107162954 B CN 107162954B
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ketone
indole
benzyl
arh
carbazole
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CN107162954A (en
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孙晶
杨仁银
颜朝国
韩莹
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Yangzhou University
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Yangzhou University
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    • 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
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/82—Carbazoles; Hydrogenated carbazoles
    • C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
    • 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
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • 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
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/94—[b, c]- or [b, d]-condensed containing carbocyclic rings other than six-membered

Abstract

A kind of synthetic method of indole-2-ketone class compound, belongs to technical field of organic synthesis.It, will in solvent and acidic catalyst under nitrogen protection effectNMethyl indol, ketone and the mixing of 3- alkylidene indol-2-one carry out cyclization dehydration to get compound.Raw material of the invention is simple and easy to get, does not need previously prepared, and reaction condition is simple, and substrate spectrum is wide, and without the participation of metallic catalyst, yield is high.

Description

A kind of synthetic method of indole-2-ketone class compound
Technical field
The invention belongs to technical field of organic synthesis.
Background technique
There is the structural framing of carbazole, some of compounds not only have biology in many nitrogenous heterocyclic natural products Activity can also be used in luminescent material.(Zhang, Y. D.; Wada, T.; Sasabe, H. J. Mater. Chem. 1998, 8, 809. Hong, M. K.; Ravva, M. K.; Winget, P.; Bredas, J. L. Chem. Mater. 2016, 28, 5791. Jiang, H. J.; Sun, J.; Zhang, J. L. Curr. Org. Chem.2012, 16, 2014.) and since carbazole compound is in the great function of every field, the study on the synthesis of carbazole structure All have great importance in terms of medicine, material science.
In early days, Fischer-Borsche utilizes multi-step synthesis carbazole compound.(Robinson, B.Chem. Rev.1969, 69, 227.) in recent years, people have developed transition metal-catalyzed intramolecular coupling synthesis synthesizing carbazole chemical combination Object.But these most of methods require to pre-process reactant.In Wayland E. Noland project in 1979 Group occurs Diels-Alder with naphthoquinones with 3- vinyl indoles and reacts, and continues through oxidation and obtains carbazole compound (Wayland E. Noland and Steven R. Wann, J . Org. Chem., 1979,44, 4403).2016 Guo Qixiang seminar reacts to obtain carbazoles using replacing 3- vinyl indoles and phenylglyoxal under chiral phosphoric acid catalysis Conjunction object (Huang, Y. W., Li X. Y., Fu L. N., and Guo Q. X.,Org. Lett.2016, 18, 6200).Equally, pretreatment synthesis 3- vinyl indoles is carried out in these synthetic methods.
Currently without polysubstituted 3- (9HCarbazole -2- base) indole-2-ketone class compound study on the synthesis document report.
Summary of the invention
Present invention aims to overcome that the above problem, a kind of simple and easy to get, succinct, the efficient, substrate using raw material is provided and is opened up Open up the synthetic method of the big indole-2-ketone class compound of range.
The technical scheme is that: it, will in solvent and acidic catalyst under nitrogen protection effectNMethyl indol, Ketone and the mixing of 3- alkylidene indol-2-one carry out cyclization dehydration, obtain 3- (9HCarbazole -2- base) indole-2-ketone class Object is closed, structural formula is as follows:
Wherein, R1For C4~C5Alkyl, any one in phenyl or substituted-phenyl；
R2For H or methylene CH2In any one；
R3For any one in H, F or Cl；
R4For any one in normal-butyl or benzyl；
R5For H, Cl, CH3、CH3Any one in O.
Reaction formula of the invention are as follows:
The reaction mechanism is as follows by the present invention:NMethyl indol and ketone carry out addition reaction in acid condition, and dehydration obtains double The double bond of alkene body A, A and 3- alkylidene indol-2-one carries out Micheal addition and obtains intermediate B, and B intramolecular addition obtains The water that C, C slough a molecule under the conditions of Bronsted acid obtains 3- (9HCarbazole -2- base) indole-2-ketone class compound.
Acid catalysis Domino reaction is that one of building polycyclic compound commonly uses effective method, and the present invention willNMethyl Yin Diindyl, ketone and 3- alkylidene indol-2-one are added at one time, and " treating different things alike " one-step method is utilized to provide for the synthesis of carbazole compound One succinct, efficient synthetic route.
Raw material of the invention is simple and easy to get, does not need previously prepared, and reaction condition is simple, and substrate spectrum is wide, is not necessarily to metal The participation of catalyst, yield are high.
Further, of the present inventionNThe molar ratio of methyl indol, ketone and 3- alkylidene indol-2-one is 1: 3: 1.Such asNMethyl indol and ketone are fed intake with the ratio of 1: 2 and 1: 1, then N- methyl indol cannot react completely, and use 1: 3 throwing Material, then can completely consumeNMethyl indol, therefore the ratio can achieve excellent effect, higher yield.
The ketone is acetophenone, melilotal, parachloroacetophenone, cyclohexanone, cycloheptanone, cyclooctanone or 1- naphthane Any one in ketone.Since the carbonyl activity in above-mentioned ketone molecule is higher, acidic catalyst catalysis under withNMethyl indol Reaction, it may be convenient to obtain 3- vinyl indoles, become conjugated diene body intermediate and participate in subsequent reactions.
The 3- alkylidene indol-2-one is 1- benzyl -3- (2- oxo -2- (p-methylphenyl) ethylidene) indoline - 2- ketone, the chloro- 3- of 1- butyl -5- (2- (4- methoxyphenyl) -2- oxo ethylidene) indole-2-ketone, the fluoro- 3- of 1- benzyl -5- (2- (4- aminomethyl phenyl) -2- oxo ethylidene) indole-2-ketone, 1- benzyl -3- (2- (4- chlorphenyl) -2- oxo ethylidene) Indole-2-ketone, 1- benzyl -5- methyl -3- (2- (phenyl) -2- oxo ethylidene) indole-2-ketone or 1- benzyl -5- are chloro- One of 3- (2- (4- aminomethyl phenyl) -2- oxo ethylidene) indole-2-ketone.3- alkylidene indol-2-one is due to having With the electron deficient double bond of ketone carbonyl conjugation, double bond and carbonyl are easy to happen cyclization reaction, can advantageously construct containing indoles Structural compounds.The present invention utilizesNThree component reactions of methyl indol and ketone and 3- alkylidene indol-2-one, a step construct Carbazole indoline-like compound.This method is easy to operate and yield is good.
The solvent is dry toluene.Using the specific product, synthetic yield is made to reach 62%~90%.
In order to guarantee that higher synthetic yield, the acidic catalyst are trifluoromethane sulfonic acid.
The molar ratio of the trifluoromethane sulfonic acid and 3- alkylidene indol-2-one is 0.05: 1.The catalyst is this The necessary auxiliary reagent of reaction, excessive catalyst waste of resource, very few catalyst cannot be catalyzed reaction completely, this feeds intake Ratio can achieve good catalytic effect.
The temperature condition of the cyclization dehydration is 0~120 DEG C, is reacted 4~24 hours.Preferred reaction temperature is It 80 DEG C, reacts 16 hours.Because low temperature the reaction time is too long, reaction is not thorough；Temperature is excessively high, generates by-product, influences to produce Rate.Experiment shows that at such a temperature, reaction rate is most fast, yield highest.
Water is added to system after reaction in the higher product of purity in order to obtain, after being extracted with ethyl acetate, merges Organic layer, then by organic layer anhydrous Na2SO4It is dry, then filtered through decompression, by filtrate rotary evaporation, using ethyl acetate and gently Petroleum ether obtains 3- (9 as solvent, by silica gel column layer chromatographic isolationHCarbazole -2- base) indole-2-ketone class compound Sterling.
Specific embodiment
Below with reference to embodiment, the present invention is described in more detail, but protection scope of the present invention is not limited only to these realities Apply example.
Embodiment 1: the following 1- benzyl -3- (9- methyl 4-phenyl -1- (p-methylphenyl) -9 of preparation structure formulaHClick Azoles -2- base) indole-2-ketone, reaction equation is as follows:
The preparation method is as follows:
Under the protection of nitrogen, 0.5 mmol(0.066g is added in the Shrek pipe (Schlenck) of 10 mL) N- first Base indoles, 1.5 mmol ketone, 2 mL dry toluenes, 0.5 mmol(0.176g) (2- oxo -2- is (to methylbenzene by 1- benzyl -3- Base) ethylidene) indole-2-ketone and 5 mol%(0.004g) trifluoromethanesulfonic acid, it is warming up to 80 DEG C and is stirred to react 36 hours.TLC Reaction process is detected, when after reaction, 5mL water is added to system, is extracted with ethyl acetate (5mL × 3), merges organic layer, Organic layer anhydrous Na2SO4Dry, decompression filters, by filtrate rotary evaporation, using ethyl acetate and light sherwood oil as expansion Agent obtains 1- benzyl -3- (9- methyl 4-phenyl -1- (p-methylphenyl) -9 by silica gel column layer chromatographic isolationHCarbazole -2- Base) indole-2-ketone, separation yield 83%, 0.236 g.
Structural characterization data are as follows:
m.p. 219-221℃; 1H NMR (400 MHz, CDCl3) δ: 7.81 (d, J = 7.6 Hz, 1H, ArH), 7.57-7.44 (m, 6H, ArH), 7.39-7.27 (m, 8H, ArH), 7.24-7.20 (m, 2H, ArH), 7.11 (t, J = 7.6 Hz, 1H, ArH), 7.04 (d, J = 7.6 Hz, 1H, ArH), 6.95-6.93 (m, 1H, ArH), 6.92-6.90 (m, 1H, ArH), 6.71 (d, J = 8.0 Hz, 1H, ArH), 6.44 (s, 1H, ArH), 5.00 (d, J = 15.6 Hz, 1H, CH), 4.86-4.81 (m, 2H, CH), 3.29 (s, 3H, CH3), 2.47 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ: 177.0, 143.3, 142.3, 141.0, 139.1, 137.7, 137.1, 136.0, 134.9, 134.0, 132.1, 131.1, 130.7, 129.3, 128.8, 128.6, 127.8, 127.5, 127.4, 127.3, 125.6, 125.4, 124.6, 122.6, 122.1, 122.0, 120.0, 119.6, 118.6, 108.9, 108.5, 48.8, 43.8, 32.1, 21.3; IR (KBr) υ: 3026, 2921, 1710, 1609, 1560, 1474, 1349, 1326, 1270, 1225, 1165, 1124, 1071, 1017, 910, 831, 741, 700 cm-1; MS (m/z): HRMS (ESI) theoretical value C41H33N2O([M+H]+): 569.2593. measured value 569.2579.
Embodiment 2: the preparation structure formula following chloro- 3- of 1- normal-butyl -5- (1- (4- methoxyphenyl) -9- methyl -4- benzene Base-9HCarbazole -2- base) indole-2-ketone:
In embodiment 1,1- benzyl -3- used (2- oxo -2- (p-methylphenyl) ethylidene) indole-2-ketone is used The chloro- 3- of 1- butyl -5- (2- (4- the methoxyphenyl) -2- oxo ethylidene) indole-2-ketone of equimolar amounts is replaced, other steps Rapid method is identical as example 1, obtains the chloro- 3- of 1- normal-butyl -5- (1- (4- methoxyphenyl) -9- methyl 4-phenyl -9HClick Azoles -2- base) indole-2-ketone, separation yield 80%, 0.234 g.
Structural characterization data are as follows:
m.p. 204-206℃; 1H NMR (600 MHz, CDCl3) δ: 7.81 (s, 1H, ArH), 7.51- 7.46 (m, 6H, ArH), 7.37-7.35 (m, 1H, ArH), 7.30 (brs, 2H, ArH), 7.18 (brs, 1H, ArH), 7.09-7.07 (m, 2H, ArH), 7.00 (s, 1H, ArH), 6.94-6.92 (m, 1H, ArH), 6.74 (s, 1H, ArH), 6.37 (s, 1H, ArH), 4.71 (s, 1H, CH), 3.90 (s, 3H, OCH3), 3.72-3.67 (m, 2H, CH), 3.30 (s, 3H, CH3), 1.63 (brs, 2H, CH), 1.36 (brs, 2H, CH), 0.92 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ: 176.3, 159.4, 142.3, 140.9, 139.3, 137.2, 133.4, 133.3, 132.9, 131.8, 129.8, 129.3, 128.3, 127.8, 127.6, 127.5, 125.5, 125.4, 125.0, 122.1, 121.9, 120.3, 119.3, 118.7, 113.8, 109.0, 108.6, 55.3, 48.8, 40.0, 32.2, 29.4, 20.2, 13.7; IR (KBr) υ: 3059, 3003, 2929, 2864, 1717, 1605, 1561, 1517, 1476, 1436, 1378, 1332, 1275, 1243, 1177, 1112, 1070, 1030, 914, 876, 837, 804, 747, 703 cm-1; MS (m/z): HRMS (ESI) theoretical value Calcd. for C38H34ClN2O2 ([M+H]+): 585.2309. measured value 585.2298.
Embodiment 3: the following fluoro- 3- of the 1- benzyl -5- (9- methyl 4-phenyl -1- (p-methylphenyl) -9 of preparation structure formulaH- Carbazole -2- base) indole-2-ketone:
In embodiment 1,1- benzyl -3- used (2- oxo -2- (p-methylphenyl) ethylidene) indole-2-ketone It is replaced with the fluoro- 3- of 1- benzyl -5- (2- (4- the aminomethyl phenyl) -2- oxo ethylidene) indole-2-ketone of equimolar amounts, other steps Rapid method is identical as example 1, obtains the fluoro- 3- of 1- benzyl -5- (9- methyl 4-phenyl -1- (p-methylphenyl) -9HCarbazole -2- base) Indole-2-ketone, separation yield 78%, 0.229 g.
Structural characterization data are as follows:
m.p. 207-209℃; 1H NMR (400 MHz, CDCl3) δ: 7.81 (d, J = 7.2 Hz, 1H, ArH), 7.51-7.46 (m, 7H, ArH), 7.39-7.33 (m, 5H, ArH), 7.31-7.28 (m, 4H, ArH), 6.94 (t, J = 7.6 Hz, 1H, ArH), 6.82-6.78 (m, 2H, ArH), 6.60 (brs, 1H, ArH), 6.42 (s, 1H, ArH), 4.99 (d, J = 15.2 Hz, 1H, CH), 4.83-4.80 (m, 2H, CH), 3.29 (s, 3H, CH3), 2.48 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ: 176.8, 159.3 (d, J = 239.2 Hz), 142.3, 140.9, 139.2, 139.2, 137.9, 137.2, 135.7, 134.7, 133.3, 132.8, 132.7, 132.0, 130.7, 129.4, 129.3, 128.9, 128.7, 128.3, 127.6, 127.5, 127.3, 125.6, 125.5, 122.2, 121.9, 119.4, 118.7, 114.2 (d, J = 23.6 Hz), 112.7 (d, J = 25.2 Hz), 109.3, 108.6, 49.1, 43.9, 32.1, 21.3; IR (KBr) υ: 3032, 2925, 1709, 1614, 1562, 1525, 1484, 1454, 1378, 1331, 1270, 1224, 1166, 1125, 1071, 1019, 945, 909, 876, 821, 752 cm-1; MS (m/z): HRMS (ESI) theoretical value C41H32FN2O([M+H]+): 587.2499. measured value 587.2485.
Embodiment 4: the following 1- benzyl -3- of preparation structure formula (1- (4- chlorphenyl) -9- methyl -4- (p-methylphenyl) - 9HCarbazole -2- base) indole-2-ketone:
In embodiment 1,1- benzyl -3- used (2- oxo -2- (p-methylphenyl) ethylidene) indole-2-ketone is used 1- benzyl -3- (2- (4- the chlorphenyl) -2- oxo ethylidene) indole-2-ketone of equimolar amounts is replaced, acetophenone equimolar The melilotal of amount is replaced, other step methods are identical as example 1, obtain 1- benzyl -3- (1- (4- chlorphenyl) -9- first Base -4- (p-methylphenyl) -9HCarbazole -2- base) indole-2-ketone, separation yield 70%.0.211 g.
Structural characterization data are as follows:
m.p. 238-240℃; 1H NMR (400 MHz, CDCl3) δ: 7.94 (d, J = 7.6 Hz, 1H, ArH), 7.56 (d, J = 7.6 Hz, 1H, ArH), 7.52 (brs, 2H, ArH), 7.42-7.36 (m, 5H, ArH), 7.31-7.27 (m, 7H, ArH), 7.14-7.10 (m, 1H, ArH), 7.02-7.01 (m, 1H, ArH), 6.98-6.91 (m, 2H, ArH), 6.72 (d, J = 7.6 Hz, 1H, ArH), 6.42 (s, 1H, ArH), 4.98 (d, J = 15.6 Hz, 1H, CH), 4.85 (d, J = 15.2 Hz, 1H, CH), 4.71 (s, 1H, CH), 3.30 (s, 3H, CH3), 2.46 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ: 176.7, 143.4, 142.3, 139.0, 137.8, 137.6, 137.2, 136.6, 135.9, 134.1, 133.8, 133.7, 132.1, 130.8, 129.1, 128.7, 128.3, 128.0, 127.5, 127.3, 125.5, 124.6, 124.0, 122.7, 122.2, 122.0, 120.4, 119.7, 118.8, 109.0, 108.6, 48.7, 43.8, 32.4, 21.3; IR (KBr) υ: 3029, 2922, 2857, 1712, 1609, 1561, 1467, 1366, 1318, 1240, 1172, 1124, 1089, 1011, 912, 826, 742 cm-1; MS (m/z): HRMS (ESI) theoretical value C41H32ClN2O([M+H]+): 603.2203. measured value 603.2200.
Embodiment 5: (9- methyl-1-phenyl-4- is (to methylbenzene by the following 1- benzyl-5- methyl-3- of preparation structure formula Base)-9HCarbazole -2- base) indole-2-ketone:
In example 4,1- benzyl -3- used (2- (4- chlorphenyl) -2- oxo ethylidene) indole-2-ketone use etc. 1- benzyl -5- methyl -3- (2- (the phenyl) -2- oxo ethylidene) indole-2-ketone of mole is replaced, other step methods with Example 4 is identical, obtains 1- benzyl-5- methyl-3- (9- methyl-1-phenyl-4- (p-methylphenyl)-9HCarbazole -2- base) indoles Quinoline -2- ketone, separation yield 66%, 0.192 g.
Structural characterization data are as follows:
m.p. 215-217℃; 1H NMR (400 MHz, CDCl3) δ: 7.94 (d, J = 7.6 Hz, 1H, ArH), 7.61-7.55 (m, 2H, ArH), 7.52-7.41 (m, 5H, ArH), 7.38-7.29 (m, 4H, ArH), 7.27-7.21 (m, 5H, ArH), 6.95 (t, J = 7.2 Hz, 1H, ArH), 6.89 (d, J = 8.0 Hz, 1H, ArH), 6.86 (s, 1H, ArH), 6.58 (d, J = 7.6 Hz, 1H, ArH), 6.44 (s, 1H, ArH), 4.99 (d, J = 15.2 Hz, 1H, CH), 4.79 (d, J = 15.6 Hz, 1H, CH), 4.74 (s, 1H, CH), 3.25 (s, 3H, CH3), 2.46 (s, 3H, CH3), 2.19 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ: 176.9, 142.4, 141.0, 139.1, 138.1, 138.0, 137.3, 137.1, 136.2, 134.0, 132.4, 132.2, 131.2, 130.9, 129.2, 128.6, 128.6, 128.1, 128.0, 127.4, 127.3, 125.4, 125.4, 122.2, 122.1, 120.2, 119.8, 119.7, 118.6, 108.6, 108.5, 48.8, 43.8, 32.1, 21.3, 21.0; IR (KBr) υ: 3029, 2926, 2859, 1708, 1606, 1560, 1492, 1376, 1331, 1270, 1224, 1179, 1122, 1074, 1018, 904, 813, 741, 700 cm-1; MS (m/z): HRMS (ESI) theoretical value C42H35N2O([M+H]+): 583.2749. measured value 583.2739.
Embodiment 6: the following 1- benzyl-3- of preparation structure formula (4- (4- chlorphenyl)-9- methyl-1-(p-methylphenyl)-9HCarbazole -2- base) indole-2-ketone:
In embodiment 1, the parachloroacetophenone replacement of acetophenone equimolar amounts used, other step methods and example 1 is identical, obtains 1- benzyl-3- (4- (4- chlorphenyl)-9- methyl-1-(p-methylphenyl)-9HCarbazole -2- base) indoline -2- Ketone, separation yield 84%, 0.253 g.
Structural characterization data are as follows:
m.p. 224-226℃; 1H NMR (600 MHz, CDCl3) δ: 7.80 (s, 1H, ArH), 7.42- 7.37 (m, 10H, ArH), 7.30-7.24 (m, 5H, ArH), 7.12 (s, 1H, ArH), 7.02 (s, 1H, ArH), 6.97-6.92 (m, 2H, ArH), 6.73 (s, 1H, ArH), 6.39 (s, 1H, ArH), 5.01 (d,J = 15.6 Hz, 1H, CH), 4.82-4.80 (m, 2H, CH), 3.28 (s, 3H, CH3), 2.47 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ: 177.0, 143.3, 142.3, 139.4, 137.8, 136.0, 135.7, 134.7, 134.1, 133.4, 132.0, 131.1, 130.6, 129.3, 128.8, 128.6, 128.4, 127.8, 127.5, 127.3, 126.0, 125.5, 124.6, 122.6, 121.9, 121.7, 119.9, 119.4, 118.8, 108.9, 108.7, 48.8, 43.8, 32.1, 21.3; IR (KBr) υ: 3056, 2951, 2919, 1714, 1608, 1562, 1475, 1354, 1268, 1227, 1171, 1122, 1090, 1013, 973, 911, 826, 791, 740 cm-1; MS (m/z): HRMS (ESI) theoretical value C41H32ClN2O([M+H]+): 603.2203. Measured value 603.2197.
Embodiment 7: the following chloro- 3- of 1- benzyl -5- of preparation structure formula (7- methyl -6- (p-methylphenyl) -2,3,4,7- four Hydrogen -1HBenzo [c] carbazole -5- base) indole-2-ketone:
In embodiment 3, the fluoro- 3- of 1- benzyl -5- used (2- (4- aminomethyl phenyl) -2- oxo ethylidene) indoline - The chloro- 3- of 1- benzyl -5- (2- (4- the aminomethyl phenyl) -2- oxo ethylidene) indole-2-ketone of 2- ketone equimolar amounts is replaced, benzene The cyclohexanone of ethyl ketone equimolar amounts is replaced, other step methods are identical as example 3, obtain 1- benzyl -5- chloro- 3- (7- methyl - 6- (p-methylphenyl) -2,3,4,7- tetrahydro -1HBenzo [c] carbazole -5- base) indole-2-ketone, separation yield 78%, 0.226 g。
Structural characterization data are as follows:
m.p. 242-244℃; 1H NMR (400 MHz, CDCl3) δ: 8.21 (d, J = 8.0 Hz, 1H, ArH), 7.54 (d, J = 7.2 Hz, 1H, ArH), 7.45 (t, J = 7.6 Hz, 1H, ArH), 7.40-7.27 (m, 9H, ArH), 7.22 (t, J = 7.6 Hz, 1H, ArH), 7.11 (d, J = 8.4 Hz, 1H, ArH), 6.91 (s, 1H, ArH), 6.69 (d, J = 8.4 Hz, 1H, ArH), 5.10 (d, J = 15.6 Hz, 1H, CH), 4.99 (s, 1H, CH), 4.78 (d, J = 15.2 Hz, 1H, CH), 3.40-3.39 (m, 2H, CH), 3.17 (s, 3H, CH3), 2.44 (s, 3H, CH3), 2.25-2.18 (m, 1H, CH), 1.89-1.83 (m, 2H, CH), 1.79-1.72 (m, 1H, CH), 1.62-1.59 (m, 1H, CH), 1.52-1.49 (m, 1H, CH); 13C NMR (100 MHz, CDCl3) δ: 176.3, 142.3, 141.1, 137.8, 137.0, 136.1, 135.6, 132.8, 131.5, 131.3, 130.5, 129.4, 129.1, 128.7, 127.8, 127.7, 127.3, 126.6, 125.9, 124.9, 123.5, 123.2, 122.8, 121.4, 118.7, 109.6, 108.4, 49.6, 44.2, 31.8, 28.7, 26.1, 22.9, 22.5, 21.3; IR (KBr) υ: 3035, 2931, 2868, 1717, 1606, 1480, 1324, 1252, 1164, 1114, 1022, 932, 821, 743, 698 cm-1; MS (m/z): HRMS (ESI) theoretical value C39H34ClN2O([M+H]+): 581.2360. measured value 581.2350.
Embodiment 8: the following chloro- 3- of 1- benzyl -5- of preparation structure formula (8- methyl -7- (p-methylphenyl) -1,2,3,4,5, 8- hexahydro cycloheptyl simultaneously [c] carbazole -6- base) indole-2-ketone:
In embodiment 7, the cycloheptanone of cyclohexanone equimolar amounts used is replaced, other step methods and 7 phase of example Together, obtain the chloro- 3- of 1- benzyl -5- (8- methyl -7- (p-methylphenyl) -1,2,3,4,5,8- hexahydro cycloheptyls simultaneously [c] carbazole -6- base) Indole-2-ketone, separation yield 71%.0.211 g.
Structural characterization data are as follows:
m.p. 238-240℃; 1H NMR (400 MHz, CDCl3) δ: 8.31 (d, J = 8.0 Hz, 1H, ArH), 7.56 (d, J = 7.6 Hz, 1H, ArH), 7.43 (t, J = 7.6 Hz, 1H, ArH), 7.38-7.27 (m, 9H, ArH), 7.20 (t, J = 7.6 Hz, 1H, ArH), 7.09 (d, J = 8.4 Hz, 1H, ArH), 6.89 (s, 1H, ArH), 6.66 (d, J = 8.4 Hz, 1H, ArH), 4.99 (d, J = 15.6 Hz, 1H, CH), 4.96 (s, 1H, CH), 4.87 (d, J = 15.6 Hz, 1H, CH), 3.53-3.49 (m, 2H, CH), 3.14 (s, 3H, CH3), 2.44 (s, 3H, CH3), 2.26-2.20 (m, 1H, CH), 2.16-2.10 (m, 1H, CH), 1.84-1.77 (m, 2H, CH), 1.72-1.66 (m, 2H, CH), 1.22-1.15 (m, 1H, CH), 1.06-1.01 (m, 1H, CH); 13C NMR (100 MHz, CDCl3) δ: 176.7, 142.7, 140.8, 139.0, 137.7, 136.5, 135.7, 133.4, 132.8, 131.6, 130.6, 129.9, 129.4, 129.0, 128.7, 127.8, 127.7, 127.2, 125.3, 125.1, 123.8, 122.5, 121.3, 118.7, 109.7, 108.6, 49.7, 44.3, 31.9, 31.4, 30.3, 26.6, 25.9, 24.1, 21.4; IR (KBr) υ: 3025, 2921, 2855, 1721, 1605, 1481, 1440, 1390, 1329, 1252, 1163, 1113, 1077, 1026, 949, 816, 742, 701 cm-1; MS (m/z): HRMS (ESI) theoretical value C40H36ClN2O([M+H]+): 595.2516. Measured value 595.2516.
Embodiment 9: the following chloro- 3- of 1- benzyl -5- of preparation structure formula (9- methyl -8- (p-methylphenyl) -2,3,4,5,6, 9- hexahydro -1HRing it is pungent simultaneously [c] carbazole -7- base) indole-2-ketone:
In embodiment 7, the cyclooctanone of cyclohexanone equimolar amounts used is replaced, other step methods and 7 phase of example Together, 1- benzyl -5- chloro- 3- (9- methyl -8- (p-methylphenyl) -2,3,4,5,6,9- hexahydros -1 are obtainedHRing it is pungent simultaneously [c] carbazole- 7- yl) indole-2-ketone, separation yield 62%, 0.189 g.
Structural characterization data are as follows:
m.p. 246-248℃; 1H NMR (400 MHz, CDCl3) δ: 8.22 (d, J = 8.0 Hz, 1H, ArH), 7.57 (d, J = 7.2 Hz, 1H, ArH), 7.45 (t, J = 7.6 Hz, 1H, ArH), 7.37 (t,J = 8.0 Hz, 1H, ArH), 7.34-7.28 (m, 7H, ArH), 7.22 (t, J = 7.6 Hz, 1H, ArH), 7.10 (d, J = 7.6 Hz, 1H, ArH), 6.87 (s, 1H, ArH), 6.67 (d, J = 8.4 Hz, 1H, ArH), 5.03 (s, 1H, CH), 4.96 (d, J = 14.8 Hz, 1H, CH), 4.91 (d, J = 15.6 Hz, 1H, CH), 3.44-3.35 (m, 2H, CH), 3.15 (s, 3H, CH3), 2.44 (s, 3H, CH3), 2.34- 2.28 (m, 2H, CH), 2.03-1.97 (m, 2H, CH), 1.37-1.31 (m, 4H, CH), 1.26-1.24 (m, 1H, CH), 0.90-0.84 (m, 1H, CH); 13C NMR (100 MHz, CDCl3) δ: 176.6, 142.5, 140.9, 137.7, 136.8, 136.6, 135.6, 132.8, 131.6, 130.8, 130.7, 130.6, 129.4, 129.0, 128.7, 127.8, 127.7, 127.2, 126.3, 125.0, 123.8, 122.8, 122.1, 121.2, 118.9, 109.7, 108.5, 49.9, 44.3, 31.8, 30.6, 28.5, 28.4, 28.3, 26.6, 26.5, 21.3; IR (KBr) υ: 3055, 2923, 2856, 1718, 1603, 1576, 1482, 1441, 1392, 1328, 1256, 1163, 1111, 1072, 1027, 977, 926, 883, 820, 742, 700 cm-1; MS (m/z): HRMS (ESI) theoretical value C41H38ClN2O([M+H]+): 609.2673. measured value 609.2668.
Embodiment 10: the preparation structure formula following chloro- 3- of 1- benzyl -5- (9- methyl -8- (p-methylphenyl) -6,9- dihydro - 5HBenzo [2,1-c] carbazole -7- base) indole-2-ketone:
In embodiment 7, the 1-tetralone of cyclohexanone equimolar amounts used is replaced, other step methods and reality Example 7 is identical, obtains the chloro- 3- of 1- benzyl -5- (9- methyl -8- (p-methylphenyl) -6,9- dihydro -5HBenzo [2,1-c] carbazole -7- Base) indole-2-ketone, separation yield 90%, 0.283 g.
Structural characterization data are as follows:
m.p. 256-258℃; 1H NMR (400 MHz, CDCl3) δ: 8.35 (d, J = 8.0 Hz, 1H, ArH), 8.20 (d, J = 7.2 Hz, 1H, ArH), 7.65 (d, J = 6.4 Hz, 1H, ArH), 7.44-7.40 (m, 2H, ArH), 7.37-7.34 (m, 4H, ArH), 7.33-7.27 (m, 5H, ArH), 7.24-7.21 (m, 2H, ArH), 7.10 (d, J = 8.0 Hz, 1H, ArH), 7.06-7.02 (m, 1H, ArH), 6.91 (s, 1H, ArH), 6.71 (d, J = 8.4 Hz, 1H, ArH), 5.12 (d, J = 14.8 Hz, 1H, CH), 5.00 (s, 1H, CH), 4.76 (d, J = 15.2 Hz, 1H, CH), 3.20 (s, 3H, CH3), 2.60-2.57 (m, 1H, CH), 2.45 (s, 3H, CH3), 2.41-2.37 (m, 1H, CH), 1.98 (brs, 1H, CH), 1.74-1.67 (m, 1H, CH); 13C NMR (100 MHz, CDCl3) δ: 176.1, 142.7, 141.0, 139.3, 138.7, 138.0, 135.9, 135.6, 134.0, 131.6, 131.5, 131.4, 130.5, 129.8, 129.7, 129.4, 129.1, 128.7, 128.4, 128.0, 127.9, 127.8, 127.4, 126.9, 125.7, 125.6, 123.8, 122.9, 121.7, 119.4, 118.0, 109.7, 108.7, 49.4, 44.2, 32.1, 29.3, 26.3, 21.3; IR (KBr) υ: 3036, 2922, 2855, 1717, 1605, 1482, 1440, 1329, 1253, 1163, 1110, 1075, 1027, 926, 821, 740 cm-1; MS (m/z): HRMS (ESI) theoretical value C43H33ClN2NaO([M+ Na]+): 651.2179. measured value 651.2170.

Claims (7)

1.3-(9HCarbazole -2- base) indole-2-ketone class compound synthetic method, it is characterised in that: nitrogen protection act on Under, it, will in dry toluene and trifluoromethane sulfonic acidNMethyl indol, ketone and the mixing of 3- alkylidene indol-2-one carry out cyclization Dehydration obtains 3- (9HCarbazole -2- base) indole-2-ketone class compound, structural formula is as follows:
Wherein,
R3For any one in H, F or Cl；
R4For any one in normal-butyl or benzyl；
R5For H, Cl, CH3、CH3Any one in O；
The ketone is cyclohexanone, cycloheptanone, cyclooctanone or 1-tetralone；
The 3- alkylidene indol-2-one be 1- benzyl -3- (2- oxo -2- (p-methylphenyl) ethylidene) indole-2-ketone, The chloro- 3- of 1- butyl -5- (2- (4- methoxyphenyl) -2- oxo ethylidene) indole-2-ketone, the fluoro- 3- of 1- benzyl -5- (2- (4- Aminomethyl phenyl) -2- oxo ethylidene) indole-2-ketone, 1- benzyl -3- (2- (4- chlorphenyl) -2- oxo ethylidene) indoles One of quinoline -2- ketone or the chloro- 3- of 1- benzyl -5- (2- (4- aminomethyl phenyl) -2- oxo ethylidene) indole-2-ketone.
2.3-(9HCarbazole -2- base) indole-2-ketone class compound synthetic method, it is characterised in that: nitrogen protection act on Under, it, will in dry toluene and trifluoromethane sulfonic acidNMethyl indol, ketone and the mixing of 3- alkylidene indol-2-one carry out cyclization Dehydration obtains 3- (9HCarbazole -2- base) indole-2-ketone class compound, structural formula is as follows:
Wherein, R1For any one in phenyl or p-methylphenyl；
R2For H；
R3For any one in H, F or Cl；
R4For any one in normal-butyl or benzyl；
R5For H, Cl, CH3、CH3Any one in O；
The ketone is acetophenone, melilotal, any one in parachloroacetophenone；
The 3- alkylidene indol-2-one be 1- benzyl -3- (2- oxo -2- (p-methylphenyl) ethylidene) indole-2-ketone, The chloro- 3- of 1- butyl -5- (2- (4- methoxyphenyl) -2- oxo ethylidene) indole-2-ketone, the fluoro- 3- of 1- benzyl -5- (2- (4- Aminomethyl phenyl) -2- oxo ethylidene) indole-2-ketone, 1- benzyl -3- (2- (4- chlorphenyl) -2- oxo ethylidene) indoles One of quinoline -2- ketone or the chloro- 3- of 1- benzyl -5- (2- (4- aminomethyl phenyl) -2- oxo ethylidene) indole-2-ketone.
3. synthetic method according to claim 1 or 2, it is characterised in that: describedNMethyl indol, ketone and 3- alkylidene Yin The molar ratio of diindyl -2- ketone is 1: 3: 1.
4. synthetic method according to claim 3, it is characterised in that: the trifluoromethane sulfonic acid and 3- alkylidene indoles- The molar ratio of 2- ketone is 0.05: 1.
5. synthetic method according to claim 4, it is characterised in that: the temperature condition of the cyclization dehydration is 0 It~120 DEG C, reacts 4~36 hours.
6. synthetic method according to claim 5, it is characterised in that: the reaction temperature of the cyclization dehydration is 80 DEG C, it reacts 16 hours.
7. synthetic method according to claim 1 or 2, it is characterised in that: after reaction, water is added to system, uses second After acetoacetic ester extraction, merge organic layer, then by organic layer anhydrous Na2SO4It is dry, then filtered through decompression, filtrate is rotated and is steamed Hair, using ethyl acetate and light sherwood oil as solvent, obtains 3- (9 by silica gel column layer chromatographic isolationHCarbazole -2- base) Indole-2-ketone class pure compounds.
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CN106831802A (en) * 2017-04-12 2017-06-13 扬州大学 A kind of synthetic method of the benzofuran compounds of spiral shell indoline four

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