CN116791110A - Method for electrocatalytic synthesis of benzimidazoloisoquinoline analogue - Google Patents

Method for electrocatalytic synthesis of benzimidazoloisoquinoline analogue Download PDF

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CN116791110A
CN116791110A CN202210244446.3A CN202210244446A CN116791110A CN 116791110 A CN116791110 A CN 116791110A CN 202210244446 A CN202210244446 A CN 202210244446A CN 116791110 A CN116791110 A CN 116791110A
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benzo
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hydrogen
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李江胜
戴嘉颖
高伊涵
赵子信
李志伟
卢翠红
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Changsha University of Science and Technology
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    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
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    • C—CHEMISTRY; METALLURGY
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    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
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Abstract

The invention relates to a preparation method of a trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative, which comprises the following steps: 1-allyl-2-phenyl-1H-benzo [ d ] imidazole compound, sodium trifluoromethylsulfinate, acid and solvent are mixed for electrolytic reaction to obtain the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative. The method has the advantages of simple steps, low cost, no metal catalyst and the like, and can play an important role in the research field of benzimidazole isoquinoline derivatives.

Description

Method for electrocatalytic synthesis of benzimidazoloisoquinoline analogue
Technical Field
The invention relates to the technical field of medicine synthesis, in particular to a preparation method of a trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative.
Background
Trifluoromethyl has a unique beneficial effect in enhancing chemical and metabolic stability, bioavailability, and interactions with living beings, and has recently become a very useful tool in the fields of medicine and agrochemistry.
Polycyclic fused 5, 6-dihydrobenzo [4,5] imidazo [2,1a ] isoquinolines as one branch of benzimidazole compounds are the structural cores that constitute a variety of bioactive products. Such as 5-methyl-5, 6-dihydrobenzo [4,5] imidazo [2,1-a ] isoquinoline-8, 11-dione, is specific cytotoxic to two cancer cells (HeLa and DU 145); 5-methyl-5, 6-dihydrobenzo [4,5] imidazo [2,1-a ] isoquinolin-10-amine is capable of modulating potassium ion flux through voltage dependence, and thereby treating diseases; pentacyclic lactam 5, 6-dihydrobenzo [4,5] imidazo [2,1a ] isoquinolines are useful for the treatment of hemoglobinopathies such as beta thalassemia and sickle cell anemia.
The traditional synthesis method of 5, 6-dihydrobenzo [4,5] imidazo [2,1-a ] isoquinoline comprises two steps of synthesis of benzimidazole, palladium acetate, copper acetate, potassium carbonate and pivalic acid through intermediate phenethyl benzimidazole. However, this route has the disadvantages of requiring multiple conversions, expensive reagents, metal catalysis, etc.
Therefore, the trifluoromethyl and polycyclic fused 5, 6-dihydrobenzo [4,5] imidazo [2,1a ] isoquinoline are combined as benzimidazole compounds, and the synthesis method of the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline analogue has simple steps, low cost and simple operation, and has important significance.
Disclosure of Invention
Based on the above, the invention provides a preparation method of the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative, which has simple steps, low cost and no participation of metal catalyst.
The technical scheme for solving the technical problems is as follows.
A process for the preparation of a trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative comprising the steps of:
mixing a compound of the formula I, sodium trifluoromethylsulfinate, acid and a solvent for electrolytic reaction to obtain a compound of the formula II; the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative is shown as a formula II;
wherein X is selected from hydrogen or nitrogen; when X is hydrogen, m is any integer from 1 to 4, and n is any integer from 1 to 5; when X is nitrogen, m is any integer from 1 to 4, and n is any integer from 1 to 4;
R 1 each independently selected from hydrogen, alkyl or halogen;
R 2 each independently selected from hydrogen, alkyl, alkoxy, halogen, or trifluoromethyl;
R 3 independently selected from hydrogen and methyl.
In some of these embodiments, the trifluoromethyl benzo [4,5]]Imidazo [2,1-a ]]In the preparation method of isoquinoline derivative, R 1 Each independently selected from hydrogen, methyl, ethyl, fluoro, chloro or bromo.
In some of these embodiments, the trifluoromethyl benzo [4,5]]Imidazo [2,1-a ]]In the preparation method of isoquinoline derivative, R 2 Each independently selected from hydrogen, methyl, ethyl, methoxy, fluoro, chloro or bromo.
In some of these embodiments, the method for preparing the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative comprises the steps of using a positive electrode selected from graphite felt, graphite rod or RVC for the electrolysis reaction, and using a negative electrode selected from graphite felt, platinum sheet, iron sheet or nickel sheet for the electrolysis reaction.
In some of these embodiments, the current of the electrolytic reaction is 2-4 mA in the preparation of the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative.
In some of these embodiments, the solvent is selected from one of dichloromethane, dichloroethane, acetonitrile; or alternatively
The solvent is selected from a mixed solution of water and one of 1, 4-dioxane, acetonitrile, ethanol, methanol and hexafluoroisopropanol.
In some of these embodiments, the acid is at least one selected from the group consisting of trifluoroacetic acid, formic acid, acetic acid, and trifluoromethanesulfonic acid.
In some of these embodiments, the equivalent ratio of the acid to the compound of formula I is (1-35): 1 in the process for preparing the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative.
In some of these embodiments, the equivalent ratio of sodium trifluoromethylsulfinate to the compound of formula I is (2-4): 1 in the process for preparing a trifluoromethylbenzo [4,5] imidazo [2,1-a ] isoquinoline derivative.
In some of these embodiments, the process for preparing the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative is carried out at a temperature of from 70 to 90℃for a period of from 4 to 7 hours.
The preparation method of the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative (a compound shown in a formula II) takes a 1-allyl-2-phenyl-1H-benzo [ d ] imidazole compound (a compound shown in a formula I), sodium trifluoromethyl sulfinate and acid as raw materials, and the trifluoromethyl benzo [2,1-a ] isoquinoline derivative is directly obtained through four-component electrolysis reaction, and the raw materials are easy to obtain, do not need a metal catalyst, and are low in cost, economical and green.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a compound of formula I-1;
FIG. 2 is a nuclear magnetic resonance spectrum of a compound of formula I-1;
FIG. 3 is a nuclear magnetic resonance hydrogen spectrum of a compound of formula II-1;
FIG. 4 is a nuclear magnetic resonance hydrogen spectrum of a compound of formula II-1;
FIG. 5 is a nuclear magnetic resonance hydrogen spectrum of a compound of formula II-13;
FIG. 6 is a nuclear magnetic resonance hydrogen spectrum of the compound of formula II-13.
Detailed Description
The technical scheme of the invention is further described in detail below with reference to specific embodiments. The present invention may be embodied in many different forms and is not limited to the embodiments described herein. It should be understood that these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
In the description of the present invention, the meaning of "a plurality" is two or more, unless explicitly defined otherwise.
The weights of the relevant components mentioned in the description of the embodiments of the present invention may refer not only to the specific contents of the components, but also to the proportional relationship between the weights of the components, so long as the contents of the relevant components in the description of the embodiments of the present invention are scaled up or down within the scope of the disclosure of the embodiments of the present invention. Specifically, the weight described in the specification of the embodiment of the present invention may be mass units known in the chemical industry field such as μ g, mg, g, kg.
One embodiment of the invention provides a trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative, which has a structural formula shown in formula II:
wherein X is selected from hydrogen or nitrogen; when X is hydrogen, m is any integer from 1 to 4, and n is any integer from 1 to 5; when X is nitrogen, m is any integer from 1 to 4, and n is any integer from 1 to 4;
R 1 each independently selected from hydrogen, alkyl or halogen;
R 2 each independently selected from hydrogen, alkyl, alkoxy, halogen, or trifluoromethyl;
R 3 independently selected from hydrogen and methyl.
An embodiment of the present invention provides a method for preparing a trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative, comprising the steps of:
mixing a compound of the formula I, sodium trifluoromethylsulfinate, acid and a solvent for electrolytic reaction to obtain a compound of the formula II; the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative is shown as a formula II;
wherein X is selected from hydrogen or nitrogen; when X is hydrogen, m is any integer from 1 to 4, and n is any integer from 1 to 5; when X is nitrogen, m is any integer from 1 to 4, and n is any integer from 1 to 4;
R 1 each independently selected from hydrogen, alkyl or halogen;
R 2 each independently selected from hydrogen, alkyl, alkoxy, halogen, or trifluoromethyl;
R 3 independently selected from hydrogen and methyl.
The compound shown in the formula II is directly obtained by four-component electrolytic reaction by taking a 1-allyl-2-phenyl-1H-benzo [ d ] imidazole compound (a compound shown in the formula I), sodium triflate and acid as raw materials, and the raw materials are easy to obtain, do not need a metal catalyst, and have low cost, economy and environmental protection.
In some examples, in the preparation of the compound of formula II, R 1 Each independently selected from hydrogen, methyl, ethyl, fluoro, chloro or bromo. Further, R 1 Each independently selected from hydrogen, methyl or chlorine.
In some examples, in the preparation of the compound of formula II, R 2 Each independently selected from hydrogen, methyl, ethyl, methoxy, fluoro, chloro or bromo.
In some examples, the method for preparing the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative comprises the steps of using a positive electrode selected from graphite felt, graphite rod or RVC for electrolysis, and using a negative electrode selected from platinum sheet, iron sheet or nickel sheet for electrolysis. Optionally, the positive electrode used in the electrolysis reaction is selected from graphite felt, graphite rod or RVC, and the negative electrode used in the electrolysis reaction is selected from graphite felt or platinum sheet.
Preferably, the positive electrode used in the electrolysis reaction is graphite felt, and the negative electrode is a platinum sheet.
In some examples, the current of the electrolytic reaction is 2-4 mA in the preparation of trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivatives. Further, the current of the electrolytic reaction is 2.5-4 mA. Preferably, the current of the electrolytic reaction is 3mA.
In some examples, the solvent is selected from one of dichloromethane, dichloroethane and acetonitrile in the preparation method of the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative; or the solvent is selected from a mixed solution of water and one of 1, 4-dioxane, acetonitrile, ethanol, methanol and hexafluoroisopropanol. Optionally, the solvent is selected from a mixed solution of water and one of 1, 4-dioxane, acetonitrile, ethanol, methanol and hexafluoroisopropanol. Preferably, the solvent is a mixed solvent of acetonitrile and water. Further, the volume ratio of acetonitrile to water is 1:1.
In some examples, the acid is selected from at least one of trifluoroacetic acid, formic acid, acetic acid and trifluoromethanesulfonic acid in a process for preparing a trifluoromethylbenzo [4,5] imidazo [2,1-a ] isoquinoline derivative. Preferably, the acid is trifluoromethanesulfonic acid.
In some of these examples, the equivalent ratio of acid to compound of formula I is (1-35): 1 in the process for the preparation of trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivatives. Further, the equivalent ratio of acid to compound of formula I is (20-35): 1. Preferably, the equivalent ratio of acid to compound of formula I is 30:1.
In some of these examples, the equivalent ratio of sodium trifluoromethylsulfinate to the compound of formula I is (2-4): 1 in the process for the preparation of a trifluoromethylbenzo [4,5] imidazo [2,1-a ] isoquinoline derivative. Further, the equivalent ratio of sodium trifluoromethylsulfinate to the compound of formula I is (3-4): 1. Preferably, the equivalent ratio of sodium trifluoromethylsulfinate to the compound of formula I is 3:1.
In some examples, the process for preparing the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative comprises the step of carrying out an electrolysis reaction at a temperature of from 70 to 90℃for a period of from 4 to 7 hours. Further, the temperature of the electrolytic reaction is 80-90 ℃ and the time is 6-7 h. Preferably, the temperature of the electrolysis reaction is 80℃and the time is 6 hours.
In some examples, electrolyte may be added to the electrolytic reaction in the preparation method of the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative.
In some of these examples, trifluoromethyl benzo [4,5]]Imidazo [2,1-a ]]In the preparation method of isoquinoline derivative, electrolyte is selected from NH 4 Br、LiClO 4 、TBAB、TBAI、Bu 4 NBF 4 、Et 4 NBF 4 、Me 4 NBF 4 、NH 4 I、NH 4 PF 6 、Bu 4 NPF 6 、Et 4 NPF 6 、Me 4 NPF 6 、Bu 4 At least one of NF. Further, the electrolyte is selected from NH 4 Br or TBAB.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The following preparation methods of the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivatives according to the present invention are exemplified, and it is understood that the preparation methods of the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivatives of the present invention are not limited to the following examples.
The 1-allyl-2-phenyl-1H-benzo [ d ] imidazole used in the examples below was synthesized according to the following procedure:
substituted benzoic acid (10 mmol) and substituted 1, 2-phenylenediamine (10 mmol) were added to a flask equipped with polyphosphoric acid (PPA) (28 g) and a magnetic stirrer and the mixture was heated at 150℃to 180℃for 10 hours (oil bath). Pouring the reaction mixture into crushed ice, stirring with NH 3 Aqueous solution (60% -70%) adjusts ph=7-8. The precipitate was filtered and washed to give the crude product.
A40 mL flask was charged with substituted benzaldehyde (10 mmol) and NaHSO was added 3 (110 mmol) was heated in an oil bath and stirred to reflux temperature, then rapidly adding the substituted 1, 2-phenylenediamine ((10 mmol), after a certain period of reaction, adding ice water to quench the reaction, continuing to stir the reaction for 30 minutes, then extracting the system to obtain a solid compound, and washing 3 times with deionized water to obtain a crude product.
The resulting benzimidazole (8 mmol) and dried DMF (20 mL) were added to a flask attached to an argon balloon, and the solution was cooled to 0deg.C. NaH (640.0 mg,60wt%,16 mmol) was added in portions to the cooled system, and after stirring at 0deg.C for 30min, allyl bromide (1.935 g,16 mmol) C was added to the 0℃reaction solution, and the reaction was maintained at room temperature for 4 hours while stirring. After that, the solution was poured into ice water and extracted as usual. The crude mixture was subjected to flash column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1:10) as eluent to obtain the target precursor (60% -85% yield).
Wherein, the structural formula of the compound of the formula I-1 is as follows:
the nuclear magnetic hydrogen spectrum of the compound of the formula I-1 is shown in figure 1, and the nuclear magnetic carbon spectrum is shown in figure 2.
Example 1
(1) Synthesis of 5- (2, 2-trifluoroethyl) -5, 6-dihydrobenzo [4,5] imidazo [2,1-a ] isoquinoline from 1-allyl-2-phenyl-1H-benzo [ d ] imidazole (Compound of formula I-1) with sodium trifluoromethylsulfinate
The method specifically comprises the following steps:
to a three-necked flask equipped with a graphite rod anode and a platinum sheet cathode, 1-allyl-2-phenyl-1H-benzo [ d ] imidazole (0.1 mmol), sodium trifluoromethylsulfinate (0.3 mmol) and a solvent were successively added, and the mixture was refluxed at 80℃and reacted at a constant current of 3mA for 4 hours. Treating the reaction system with ethyl acetate and water, evaporating the organic phase under reduced pressure, and subjecting the obtained product to flash column chromatography (petroleum ether/ethyl acetate, 4:1) to obtain the target product with the structural formula shown in formula II-1; the nuclear magnetic hydrogen spectrum is shown in fig. 3, and the nuclear magnetic carbon spectrum is shown in fig. 4.
The isolation yields of the different solvents are shown in table 1:
TABLE 1
Group of Solvent(s) Yield%
1 H 2 O/Dioxane(1:1) 8
2 H 2 O/CH 3 CN(1:1) 12
3 H 2 O/EtOH(1:1) 4
4 H 2 O/CH 3 OH(1:1) 6
5 H 2 O/HFIP(1:1) 5
6 CH 3 OH Micro-quantity
7 EtOH Micro-quantity
8 Dioxane Micro-quantity
9 DCE 7
10 DCM 7
11 CH 3 CN 8
12 H 2 O/CH 3 CN(3:1) 8
13 H 2 O/CH 3 CN(1:3) 7
14 H 2 O/CH 3 CN(1:1) 15
15 H 2 O/CH 3 CN(1:1) 14
(2) The same procedure as in (1) was adopted except that electrolyte (0.01 mmol) was added; the separation yields of the different electrolytes are shown in table 2:
TABLE 2
Group of Electrolyte composition Yield%
1 NH 4 Br 15
2 LiClO 4 8
3 TBAB 18
4 TBAI 7
5 Bu 4 NBF 4 5
6 Et 4 NBF 4 6
7 Me 4 NBF 4 6
8 NH 4 I 7
9 NH 4 PF 6 8
10 Bu 4 NPF 6 6
11 Et 4 NPF 6 7
12 Me 4 NPF 6 5
13 Bu 4 NF 3
(3) The same procedure as in (2) was adopted, wherein the electrolyte was TBAB; further adding an acid (equivalent ratio of acid to compound of formula I1:1); the isolated yields of the different acids are shown in table 3:
TABLE 3 Table 3
Group of Acid(s) Yield%
1 / 18
2 CH 3 COOH 20
3 HCOOH 18
4 CF 3 COOH 21
5 CF 3 SO 3 H 23
(4) The same procedure as in (3) was followed, the acid being CF 3 SO 3 H, only differing from the equivalent ratio of the compound of formula I, isolation yields are shown in table 4:
TABLE 4 Table 4
(5) The same procedure as in (4) was followed with an equivalent ratio of acid to compound of formula I of 30:1, except that the electrodes were different and the separation yields for the different electrodes are shown in Table 5:
TABLE 5
Group of Positive electrode (+) -negative electrode Yield%
1 Graphite rod |Pt 43
2 RVC|Pt 32
3 Graphite felt |Pt 48
4 Pt|Pt Trace
5 Graphite felt|graphite felt 28
6 Graphite felt |Fe 14
7 Graphite felt |Ni 23
(6) The same procedure as in (5) was followed, except that the electrode was graphite felt |pt, except that the equivalent ratio of sodium trifluoromethylsulfinate to the compound of formula I was varied, and the isolation yields are shown in table 6:
TABLE 6
(7) The same procedure as in (5) was adopted, and the electrode was graphite felt |pt, except that only the temperature of the electrolytic reaction was different, and the separation yields were as shown in table 7:
TABLE 7
Group of Electrolysis temperature Yield%
1 70 36
2 80 48
3 90 43
(8) The same procedure as in (5) was used, the electrode was graphite felt |pt, except that the current for the electrolytic reaction was different, and the separation yield was as shown in table 8:
TABLE 8
Group of Current (mA) Yield%
1 2 32
2 2.5 41
3 3 48
4 4 50
5 Without any means for 0
(9) The same procedure as in (5) was used, the electrode was graphite felt |pt, except that the time of the electrolytic reaction was different, and the separation yields were as shown in table 9:
TABLE 9
Group of Time (h) Yield%
1 4 48
2 5 59
3 6 80
4 7 80
(10) The same procedure as in (9) was adopted, and the time of the electrolytic reaction was 6 hours, except that no electrolyte was added, and the isolation yield was 80%.
(11) The same procedure as in (9) was adopted, the time of the electrolytic reaction was 6 hours, except that the electrolytic reaction was carried out under a nitrogen atmosphere, and the isolation yield was 43%.
The preferred test conditions were obtained by the steps (1) to (11) of example 1 as follows:
to a three-necked flask equipped with a graphite felt anode and a platinum sheet cathode, 1-allyl-2-phenyl-1H-benzo [ d ] imidazole (0.1 mmol), sodium trifluoromethylsulfinate (0.3 mmol), trifluoromethanesulfonic acid (3 mmol), acetonitrile and water (1:1, 4 mL) were successively added, and the mixture was refluxed at 80℃and reacted at a constant current of 3mA for 6 hours. Treating the reaction system with ethyl acetate and water, evaporating the organic phase under reduced pressure, and subjecting the obtained product to flash column chromatography (petroleum ether/ethyl acetate, 4:1) to obtain the target product, wherein the calculated separation yield is 80%;
an oily liquid. 1 HNMR(400MHz,DMSO-d6)δ8.15(s,1H),7.71(d,J＝7.4Hz,1H),7.60(d,J＝7.8Hz,1H),7.51(s,3H),7.30-7.22(m,2H),4.61(d,J＝13.1Hz,1H),4.33(d,J＝12.9Hz,1H),3.76(s,1H),2.50(s,2H). 13 CNMR(101MHz,DMSO-d6)δ148.3,144.0,137.2,135.4,130.8,129.1,128.7,127.2(d, 1 J C-F(CF3) ＝276Hz),126.1,125.6,123.0,122.6,119.6,110.5,44.3,37.0(q, 2 J C-F(CF3) ＝27Hz),32.6(d, 3 J C-F(CF3) ＝2Hz). 19 FNMR(376MHz,DMSO-d6)δ-61.5.
Example 2
Synthesizing a compound shown in a formula II-2, replacing 1-allyl-2-phenyl-1H-benzo [ d ] imidazole in the example 1 with 1-allyl-2- (4-methylphenyl) -1H-benzo [ d ] imidazole, carrying out flash column chromatography (petroleum ether/ethyl acetate/ammonia water, 100:20:1) on the obtained product under the same reaction conditions as the example 1 to obtain a target product, and calculating the separation yield to be 83%;
oily liquidA body. 1 HNMR(400MHz,CDCl 3 )δ8.20(d,J＝7.9Hz,1H),7.85-7.82(m,1H),7.38-7.35(m,1H),7.32-7.28(m,1H),7.17(s,1H),4.54(dd,J＝12.8,1.6Hz,1H),4.23(dd,J＝12.8,4.0Hz,1H),3.59-3.56(m,1H),2.43(s,3H),2.40-2.29(m,2H). 13 CNMR(101MHz,CDCl 3 )δ148.6,144.0,141.3,136.4,134.9,129.6,128.3,126.2(d, 1 JC-F(CF3) ＝272.5Hz),126.1,123.0,122.7,119.8,109.0,43.6,37.5(q, 2 J C-F(CF3) ＝27.8Hz),33.4(d, 3 J C-F(CF3) ＝2.8Hz),21.6. 19 FNMR(376MHz,CDCl 3 )δ-63.6.
Example 3
Synthesis of a Compound of formula II-3 1-allyl-2- (4-ethylphenyl) -1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 1, with a yield of 87%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.22(d,J＝7.9Hz,1H),7.84-7.82(m,1H),7.37-7.35(m,1H),7.33-7.29(m,3H),7.18(s,1H),4.54(d,J＝12.9Hz,1H),4.23(dd,J＝12.8,3.6Hz,1H),3.60-3.58(m,1H),2.72(q,J＝7.6Hz,2H),2.43-2.25(m,2H),1.29(t,J＝7.6Hz,3H). 13 CNMR(101MHz,CDCl 3 )δ148.6,147.6,144.0,136.5,134.9,128.4,127.1,126.21(q, 1 J C-F(CF3) ＝276.1Hz),126.20,123.3,122.9,122.7,119.8,109.0,43.7,37.5(q, 2 J C-F(CF3) ＝27.7Hz),33.45(d, 3 J C-F(CF3) ＝2.5Hz),28.95,15.31. 19 FNMR(376MHz,CDCl 3 )δ-63.5.
Example 4
Synthesis of a Compound of formula II-4 1-allyl-2- (4-methoxyphenyl) -1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 1, giving a yield of 81%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.26(d,J＝8.6Hz,1H),7.83-7.80(m,1H),7.36-7.34(m,,1H),7.31-7.27(m,,2H),7.01(dd,J＝8.4,2.4Hz,1H),6.87(d,J＝2.1Hz,1H),4.52(dd,J＝12.8,1.6Hz,1H),4.22(dd,J＝12.8,3.6Hz,1H),3.89(s,3H),3.58-3.56(m,1H),2.44-2.22(m,2H). 13 CNMR(101MHz,CDCl 3 )δ161.6,148.6,143.9,138.3,134.8,128.0,126.2(d, 1 J C-F(CF3) ＝276.2Hz),122.7,119.5,118.5,114.1,113.4,108.8,55.5,43.6,37.4(q, 2 J C-F(CF3) ＝27.8Hz),33.7(d, 3 J C-F(CF3) ＝2.6Hz). 19 FNMR(376MHz,CDCl 3 )δ-63.5.
Example 5
Synthesis of a Compound of formula II-5 1-allyl-2- (4-fluorophenyl) -1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 1, with a yield of 75%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.36-8.32(m,1H),7.86-7.85(m,1H),7.38-7.33(m,3H),7.23-7.18(m,1H),7.10(d,J＝8.7Hz,1H),4.55(d,J＝13.0Hz,1H),4.28(d,J＝12.6Hz,1H),3.64(s,1H),2.47-2.30(m,2H). 13 CNMR(101MHz,CDCl 3 )δ163.9(d, 1 J C-F ＝250.6Hz),147.6,144.0,138.7(d, 3 J C-F ＝7.9Hz),134.8,128.5(d, 3 J C-F ＝8.8Hz),126.0(q, 1 J C-F(CF3) ＝276Hz),123.2,122.9,122.3(d, 4 J C-F ＝3.1Hz),119.9,116.2(d, 2 J C-F ＝21.8Hz),114.8(d, 2 J C-F ＝22.6Hz),109.0,43.6,37.3(q, 2 J C-F(CF3) ＝28.1Hz),33.4. 19 FNMR(376MHz,CDCl 3 )δ-63.5,-108.2.
Example 6
Synthesis of a Compound of formula II-6 1-allyl-2- (4- (trifluoromethyl) phenyl) -1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 1, yielding 71%;
white solid, m.p.101-102 ℃. 1 HNMR(400MHz,CDCl 3 )δ8.44(d,J＝8.1Hz,1H),7.86(d,J＝7.3Hz,1H),7.74(d,J＝8.1Hz,1H),7.63(s,1H),7.42-7.34(m,3H),4.60(d,J＝13.1Hz,1H),4.30(d,J＝13.0Hz,1H),3.72(s,1H),2.47-2.28(m,2H). 13 CNMR(101MHz,CDCl 3 )δ146.7,144.0,136.7,134.9,132.3(q, 2 J C-F(CF3,Ar) ＝32.6Hz),129.6,129.2,126.6,125.9(q, 1 J C-F(CF3) ＝276Hz),125.7(q, 3 J C-F(CF3,Ar) ＝3.8Hz),124.8(q, 3 J C-F(CF3,Ar) ＝3.6Hz),123.9,123.6(q, 1 J C-F(CF3,Ar) ＝270.9Hz),123.3,120.3,109.3,43.6,37.3(q, 2 J C-F(CF3) ＝28.1Hz),33.4(d, 3 J C-F(CF3) ＝2.3Hz). 19 FNMR(376MHz,CDCl 3 )δ-62.8,-63.4.
Example 7
Synthesis of a Compound of formula II-7, substituting 1-allyl-2- (o-tolyl) -1H-benzo [ d ] imidazole for 1-allyl-2-phenyl-1H-benzo [ d ] imidazole in example 1, and carrying out flash column chromatography (Petroleum ether/dichloromethane, 1:6) on the obtained product under the same reaction conditions as in example 1 to obtain the target product in 81% yield;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ7.30-7.87(m,1H),7.38-7.36(m,1H),7.35-7.30(m,4H),7.20-7.18(m,1H),4.54(dd,J＝12.8,1.6Hz,1H),4.22(dd,J＝13.2,3.6Hz,1H),3.60-3.54(m,1H),2.97(s),2.26-2.16(m,2H). 13 CNMR(101MHz,CDCl 3 )δ148.4,143.9,139.1,137.8,134.1,131.8,129.8,126.2(q, 1 J C-F(CF3) ＝276Hz),125.5,124.5,123.1,122.4,120.2,108.8,43.2,37.1(q, 2 J C-F(CF3) ＝27.7Hz),34.5(d, 3 J C-F(CF3) ＝2.7Hz),22.5. 19 FNMR(376MHz,CDCl 3 )δ-63.6.
Example 8
Synthesis of a Compound of formula II-8 1-allyl-2- (2-methoxyphenyl) -1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 7, with a yield of 60%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ7.92(dd,J＝7.2,2.4Hz,1H),7.43-7.39(m,1H),7.36-7.28(m,3H),7.08-7.03(m,1H),6.97(d,J＝7.5Hz,1H),4.53(dd,J＝13.2,2.0Hz,1H),4.22(dd,J＝12.8,3.6Hz,1H),4.08(s,3H),3.60-3.53(m,1H),2.25-2.18(m,2H). 13 CNMR(101MHz,CDCl 3 )δ158.2,146.1,144.0,139.2,133.5,131.5,126.1(q, 1 J C-F(CF3) ＝276Hz),123.2,122.4,120.6,119.9,114.8,111.6,108.5,56.4,43.2(d, 4 J C-F(CF3) ＝1.0Hz),36.9(q, 2 J C-F(CF3) ＝27.8Hz),34.4(d, 3 J C-F(CF3) ＝2.6Hz). 19 FNMR(376MHz,CDCl 3 )δ-63.60.
Example 9
Synthesis of a Compound of formula II-9 1-allyl-2- (2-chlorophenyl) -1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 1, with a yield of 73%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ7.98-7.95(m,1H),7.55(dd,J＝8.0,1.2Hz,1H),7.39-7.34(m,3H),7.34-7.28(m,2H),4.55(dd,J＝13.2,2.0Hz,1H),4.26(dd,J＝13.2,3.2Hz,1H),3.63-3.58(m,1H),2.23-2.13(m,2H). 13 CNMR(101MHz,CDCl 3 )δ145.5,143.7,139.5,134.0,133.3,131.8,130.6,126.6,126.0(d, 1 J C-F(CF3) ＝278Hz),124.2,123.9,122.8,120.9,108.8,43.15,36.8(q, 2 J C-F(CF3) ＝28Hz),34.7(d, 3 J C-F(CF3) ＝2.6Hz). 19 FNMR(376MHz,CDCl 3 )δ-63.5.
Example 10
Synthesis of a Compound of formula II-10 1-allyl-2- (2-bromophenyl) -1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 7, giving a yield of 76%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ7.98-7.95(m,1H),7.77(dd,J＝8.0,1.2Hz,1H),7.37-7.36(m,2H),7.34-7.30(m,2H),7.28-7.24(m,1H),4.55(dd,J＝13.2,2.0Hz,1H),4.26(dd,J＝12.8,3.6Hz,1H),3.61-3.56(m,1H),2.21-2.11(m,1H). 13 CNMR(101MHz,CDCl 3 )δ145.9,143.4,139.8,135.4,134.2,130.7,127.2,126.0(d, 1 J C-F(CF3) ＝276Hz),125.8,123.9,122.8,121.5,120.9,108.9,43.1,36.8(q, 2 J C-F(CF3) ＝27.9Hz),34.8(d, 3 J C-F(CF3) ＝2.6Hz). 19 FNMR(376MHz,CDCl 3 )δ-63.5.
Example 11
Synthesis of Compounds of formulas II-11-1 and II-11-2, substituting 1-allyl-2- (3-bromophenyl) -1H-benzo [ d ] imidazole for 1-allyl-2-phenyl-1H-benzo [ d ] imidazole in example 1, and performing flash column chromatography (Petroleum ether/ethyl acetate, 5:1) on the obtained product under the same reaction conditions as in example 1 to obtain the target product and its isomer, wherein the yields are 39% and 33%, respectively;
formula II-11-1, oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.49(d,J＝2.0Hz,1H),7.87-7.83(m,1H),7.58(dd,J＝8.4,2.4Hz,1H),7.41-7.31(m,3H),7.25(d,J＝8.0Hz,2H),4.55(dd,J＝13.2,2.4Hz,1H),4.27(dd,J＝13.2,4.0Hz,1H),3.65-3.60(m,1H),2.43-2.24(m,2H). 13 CNMR(101MHz,CDCl 3 )δ146.9,143.9,134.9,134.8,133.6,129.4,129.0,127.6,126.0(d, 1 J C-F(CF3) ＝276Hz),123.6,123.2,122.8,120.2,109.2,43.69,37.4(q, 2 J C-F(CF3) ＝28Hz),33.0(d, 3 J C-F(CF3) ＝2.5Hz). 19 FNMR(376MHz,CDCl 3 )δ-63.5.
Formula II-11-2, oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.32(d,J＝8.0Hz,1H),7.86-7.82(m,1H),7.69(dd,J＝8.0,1.0Hz,1H),7.43-7.39(m,1H),7.38-7.31(m,3H),4.72(d,J＝13.3Hz,1H),4.20(dd,J＝13.2,4.0Hz,1H),4.10(d,J＝10.7Hz,1H),2.34-2.19(m,2H). 13 CNMR(101MHz,CDCl 3 )δ147.3,144.1,135.5,134.8,134.7,130.0,128.1,126.0(q, 1 J C-F(CF3) ＝276.3Hz),125.4,123.6,123.4,123.1,120.1,109.3,42.3(d, 4 J C-F(CF3) ＝1.7Hz),34.5(q, 2 J C-F(CF3) ＝28.1Hz),33.19(d, 3 J C-F(CF3) ＝2.6Hz). 19 FNMR(376MHz,CDCl 3 )δ-63.3.
Example 12
Synthesis of a Compound of formula II-12 1-allyl-2- (pyridin-3-yl) -1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 7, yield 63%; the nuclear magnetic hydrogen spectrum is shown in fig. 5, and the nuclear magnetic carbon spectrum is shown in fig. 6.
An oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.64(dd,J＝4.8,1.6Hz,1H),8.57(dd,J＝7.6,1.6Hz,1H),7.85-7.83(m,1H),7.45-7.41(m,2H),7.38-7.31(m,2H),4.62(dd,J＝12.8,5.6Hz,1H),4.36(dd,J＝12.8,7.6Hz,1H),3.89-3.82(m,1H),3.22-3.19(m,1H),2.45-2.36(m,1H). 13 CNMR(101MHz,CDCl 3 )δ154.4,150.6,147.0,144.1,134.6,126.7(d, 1 J C-F(CF3) ＝275.6Hz),123.7,123.6,123.1,122.4,120.0,109.4,43.8,35.3(d, 3 J C-F(CF3) ＝2.5Hz),34.4(q, 2 J C-F(CF3) ＝28.7Hz). 19 FNMR(376MHz,CDCl 3 )δ-63.3.
Example 13
Synthesis of a Compound of formula II-13 1-allyl-2- (2, 4-dimethylphenyl) -1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 11, yielding 78%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ7.87-7.83(m,1H),7.37-7.32(m,1H),7.30-7.26(m,2H),7.12(s,1H),7.00(s,1H),4.51(dd,J＝12.8,1.6Hz,1H),4.17(dd,J＝12.8,3.2Hz,1H),3.56-3.45(m,1H),2.93(s,3H),2.37(s,3H),2.26-2.14(m,2H). 13 CNMR(101MHz,CDCl 3 )δ148.7,143.9,140.1,139.0,137.9,134.1,132.5,126.1,122.9,122.3,121.8,120.0,108.7,43.2(d, 4 J C-F(CF3) ＝1.0Hz),37.1(q, 2 J C-F(CF3) ＝27.6Hz),34.5(d, 3 J C-F(CF3) ＝2.6Hz),22.4,21.3. 19 FNMR(376MHz,CDCl 3 )δ-63.62.
Example 14
Synthesis of a Compound of formula II-14 1-allyl-2- (2, 4-dichlorophenyl) -1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 7, with a yield of 67%;
white solid, m.p.194-195 ℃. 1 HNMR(400MHz,CDCl 3 )δ7.96-7.93(m,1H),7.57(d,J＝2.0Hz,1H),7.36-7.35(m,2H),7.34-7.28(m,2H),4.55(dd,J＝13.2,1.6Hz,1H),4.25(dd,J＝13.2,3.2Hz,1H),3.60-3.56(m,1H),2.24-2.15(m,2H). 13 CNMR(101MHz,CDCl 3 )δ144.7,143.7,140.5,135.7,134.2,133.9,131.5,126.8,125.8(d, 1 J C-F(CF3) ＝276Hz),124.1,123.0,122.9,121.0,108.9,43.0,36.6(q, 2 J C-F(CF3) ＝28.3Hz),34.68(d, 3 J C-F(CF3) ＝2.6Hz). 19 FNMR(376MHz,CDCl 3 )δ-63.5.
Example 15
Synthesizing a compound shown in a formula II-15, replacing 1-allyl-2-phenyl-1H-benzo [ d ] imidazole in the example 1 with 1-allyl-2- (3, 4-dichlorophenyl) -1H-benzo [ d ] imidazole, carrying out flash column chromatography (petroleum ether/ethyl acetate/acetic acid, 96:24:1) on the obtained product under the same reaction conditions as the example 1 to obtain a target product with a yield of 64%;
white solid, m.p.200-201 ℃. 1 HNMR(400MHz,CDCl 3 )δ8.22(d,J＝8.4Hz,1H),7.85-7.83(m,1H),7.61(d,J＝8.4Hz,1H),7.43-7.40(m,1H),7.38-7.34(m,2H),4.73(d,J＝12.2Hz,1H),4.19(d,J＝12.4Hz,2H),2.35-2.22(m,2H). 13 CNMR(101MHz,CDCl 3 )δ146.8,144.1,135.8,135.4,134.8,131.5,130.6,126.2,125.9(d, 1 J C-F(CF3) ＝276.3Hz),125.2,123.8,123.30,120.1,109.3,42.4,34.5(q, 2 J C-F(CF3) ＝28.5Hz),31.53(d, 3 J C-F(CF3) ＝1.9Hz). 19 FNMR(376MHz,CDCl 3 )δ-63.4.
Example 16
Synthesis of Compounds of formula II-16 1-allyl-2-phenyl-1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-4-methyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 11, yield 79%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.37-8.35(m,1H),7.50-7.42(m,2H),7.35-7.33(m,1H),7.22-7.19(m,2H),7.12-7.08(m,1H),4.52(dd,J＝13.2,2.0Hz,1H),4.25(dd,J＝12.8,4.0Hz,1H),3.63-3.59(m,1H),2.74(s,3H),2.41-2.23(m,2H). 13 CNMR(101MHz,CDCl 3 )δ
147.6,143.3,136.3,134.5,130.6,130.1,128.7,127.7,126.3,126.2(q, 1 J C-F(CF3) ＝276.1Hz),126.1,123.2,122.1,106.5,43.8(d, 4 J C-F(CF3) ＝1.1Hz),37.4(q, 2 J C-F(CF3) ＝27.8Hz),33.42(d, 3 J C-F(CF3) ＝2.5Hz),16.8. 19 FNMR(376MHz,CDCl 3 )δ-63.5.
Example 17
Synthesis of a Compound of formula II-17 1-allyl-2-phenyl-1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-7-methyl-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 11, giving a yield of 71%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.33-8.31(m,1H),7.69(d,J＝8.1Hz,1H),7.50-7.43(m,2H),7.37-7.34(m,1H),7.21-7.15(t,J＝7.8Hz,1H),7.03(d,J＝7.3Hz,1H),5.08(dd,J＝12.8,2.0Hz,1H),4.44(dd,J＝13.2,4.0Hz,1H),3.62-3.58(m,1H),2.72(s,3H),2.57-2.43(m,1H),2.39-2.21(m,1H). 13 CNMR(101MHz,CDCl 3 )δ144.1,136.1,133.6,130.7,128.8,127.3,126.23,126.21(q, 1 J C-F(CF3) ＝278.2Hz),125.7,122.7,121.0,118.0,45.7,37.2(q, 2 J C-F(CF3) ＝28Hz),33.6(d, 3 J C-F(CF3) ＝2.5Hz),18.7. 19 FNMR(376MHz,CDCl 3 )δ-63.6.
Example 18
Synthesis of a Compound of formula II-18, 1-allyl-5, 6-dimethyl-2-phenyl-1H-benzo [ d ] imidazole was used instead of 1-allyl-2-phenyl-1H-benzo [ d ] imidazole in example 1, and the other reaction conditions were the same as in example 2, with a yield of 82%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.29-8.27(m,1H),7.60(s,1H),7.48-7.41(m,2H),7.35-7.33(m,1H),7.14(s,1H),4.49(dd,J＝12.8,2.0Hz,1H),4.22(dd,J＝12.8,4.0Hz,1H),3.67-3.54(m,1H),2.41(s,3H),2.40(s,3H),2.36-2.23(m,2H). 13 CNMR(101MHz,CDCl 3 )δ147.5,142.5,136.1,133.4,132.5,131.8,130.4,128.7,127.7,126.2(d, 1 J C-F(CF3) ＝276Hz),126.1,125.9,119.9,109.3,43.63,37.5(q, 2 J C-F(CF3) ＝27.7Hz),33.4(d, 3 J C-F(CF3) ＝2.4Hz),20.63,20.40. 19 FNMR(376MHz,CDCl 3 )δ-63.6.
Example 19
Synthesis of Compounds of formulas II-19 1-allyl-2-phenyl-1H-benzo [ d ] imidazole in example 1 was replaced with 1-allyl-5, 6-dichloro-2-phenyl-1H-benzo [ d ] imidazole, and the other reaction conditions were the same as in example 2, yield 77%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.27-8.24(m,1H),7.88(s,1H),7.51-7.48(m,2H),7.46(s,1H),7.39-7.36(m,1H),4.46(dd,J＝13.2,2.4Hz,1H),4.25(dd,J＝12.8,4.0Hz,1H),3.68-3.63(m,1H),2.41-2.23(m,2H). 13 CNMR(101MHz,CDCl 3 )δ150.1,143.3,136.3,134.1,131.5,129.0,127.8,127.2,126.9,126.4,126.0(d, 1 J C-F(CF3) ＝276Hz),125.1,121.0,110.4,43.9,37.5(q, 2 J C-F(CF3) ＝27.9Hz),33.2(d, 3 J C-F(CF3) ＝2.5Hz). 19 FNMR(376MHz,CDCl 3 )δ-63.4.
Example 20
Synthesis of a Compound of formula II-20 1- (2-methallyl) -2-phenyl-1H-benzo [ d ] imidazole instead of 1-allyl-2-phenyl-1H-benzo [ d ] imidazole in example 1, other reaction conditions were the same as in example 1, yield 71%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.37-8.35(m,1H),7.86-7.83(m,1H),7.50-7.45(m,3H),7.40-7.36(m,1H),7.33-7.29(m,2H),4.47(d,J＝12.9Hz,1H),3.98(d,J＝12.9Hz,1H),2.41-2.26(m,2H),1.74(s,3H). 13 CNMR(101MHz,CDCl 3 )δ148.4,143.8,140.7,134.6,130.9,128.4,126.3,126.0(q, 1 J C-F(CF3) ＝277.2Hz),125.2,124.8,123.1,122.8,119.9,109.1,49.42,41.6(q, 2 J C-F(CF3) ＝26.9Hz),36.3(d, 3 J C-F(CF3) ＝1.3Hz),22.6. 19 FNMR(376MHz,CDCl 3 )δ-59.7.
Example 21
The synthesis of the compound of formula II-21, replacing sodium triflate in example 1 with sodium difluoromethylsulfinate, and the other reaction conditions were the same as in example 11, with a yield of 53%;
an oily liquid. 1 HNMR(400MHz,CDCl 3 )δ8.34-8.32(m,1H),7.86-7.84(m,1H),7.52-7.43(m,2H),7.39-7.29(m,4H),5.79(tdd,J＝56.2,5.3,3.1Hz,1H),4.46(dd,J＝12.4,2.0Hz,1H),4.30(dd,J＝12.4,3.6Hz,1H),3.59-3.57(m,1H),2.21-2.09(m,2H). 13 CNMR(101MHz,CDCl 3 )δ148.2,143.8,136.6,134.8,130.6,128.6,127.8,126.3,125.8,123.1,122.8,119.9,115.9(t, 1 J C-F(CF2) ＝238.1Hz),109.0,44.8,37.8(t, 2 J C-F(CF2) ＝20.9Hz),33.2(t, 3 J C-F(CF2) ＝5.1Hz). 19 FNMR(376MHz,CDCl 3 )δ-115.2--118.1(m).
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples merely represent a few embodiments of the present invention, which facilitate a specific and detailed understanding of the technical solutions of the present invention, but are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. It should be understood that, based on the technical solutions provided by the present invention, those skilled in the art may obtain technical solutions through logical analysis, reasoning or limited experiments, which are all within the scope of protection of the appended claims. The scope of the patent is therefore intended to be covered by the appended claims, and the description and drawings may be interpreted as illustrative of the contents of the claims.

Claims (10)

1. A process for the preparation of a trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative comprising the steps of:
mixing a compound shown in a formula I, sodium trifluoromethylsulfinate, acid and a solvent for electrolytic reaction to obtain a trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative; the trifluoromethyl benzo [4,5] imidazo [2,1-a ] isoquinoline derivative is shown as a formula II;
wherein X is selected from hydrogen or nitrogen; when X is hydrogen, m is any integer from 1 to 4, and n is any integer from 1 to 5; when X is nitrogen, m is any integer from 1 to 4, and n is any integer from 1 to 4;
R 1 each independently selected from hydrogen, alkyl or halogen;
R 2 each independently selected from hydrogen, alkyl, alkoxy, halogen, or trifluoromethyl;
R 3 independently selected from hydrogen and methyl.
2. The process of claim 1, wherein R is 1 Each independently selected from hydrogen, methyl, ethyl, fluoro, chloro or bromo.
3. The process of claim 1, wherein R is 2 Each independently selected from hydrogen, methyl, ethyl, methoxy, fluoro, chloro or bromo.
4. A method of manufacture as claimed in any one of claims 1 to 3 wherein the positive electrode used in the electrolysis reaction is selected from graphite felt, graphite rod or RVC and the negative electrode used in the electrolysis reaction is selected from graphite felt, platinum sheet, iron sheet or nickel sheet.
5. A method according to any one of claims 1 to 3, wherein the current of the electrolytic reaction is 2 to 4mA.
6. A process according to any one of claims 1 to 3, wherein the solvent is selected from one of dichloromethane, dichloroethane and acetonitrile; or alternatively
The solvent is selected from a mixed solution of water and one of 1, 4-dioxane, acetonitrile, ethanol, methanol and hexafluoroisopropanol.
7. A method according to any one of claims 1 to 3, wherein the acid is selected from at least one of trifluoroacetic acid, formic acid, acetic acid and trifluoromethanesulfonic acid.
8. A process according to any one of claims 1 to 3, wherein the equivalent ratio of the acid to the compound of formula I is (1 to 35): 1.
9. A process according to any one of claims 1 to 3, wherein the equivalent ratio of sodium triflate to the compound of formula I is (2 to 4): 1.
10. A process according to any one of claims 1 to 3, wherein the electrolysis is carried out at a temperature of 70 to 90 ℃ for a time of 4 to 7 hours.
CN202210244446.3A 2022-03-14 2022-03-14 Method for electrocatalytic synthesis of benzimidazoloisoquinoline analogue Pending CN116791110A (en)

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