CN108997145B - Method for catalyzing aromatic secondary amine trifluoroethylation by ferriporphyrin - Google Patents

Method for catalyzing aromatic secondary amine trifluoroethylation by ferriporphyrin Download PDF

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CN108997145B
CN108997145B CN201810767858.9A CN201810767858A CN108997145B CN 108997145 B CN108997145 B CN 108997145B CN 201810767858 A CN201810767858 A CN 201810767858A CN 108997145 B CN108997145 B CN 108997145B
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secondary amine
aromatic secondary
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trifluoroethylation
ferriporphyrin
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CN108997145A (en
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刘强
许桂铭
郭灿城
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Yuanjiang Hualong Catalyst Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
    • C07C209/22—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of other functional groups
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    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
    • B01J31/2208—Oxygen, e.g. acetylacetonates
    • B01J31/2217—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
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    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/26—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
    • B01J31/28—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24 of the platinum group metals, iron group metals or copper
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    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
    • B01J2231/4283—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using N nucleophiles, e.g. Buchwald-Hartwig amination
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    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
    • B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution
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    • B01J2531/84—Metals of the iron group
    • B01J2531/842—Iron

Abstract

The invention provides a method for catalyzing aromatic secondary amine trifluoroethylation by ferriporphyrin, which comprises the steps of firstly adding trifluoroethylamine salt and nitrite to carry out diazotization reaction in an acidic solution system, and then adding aromatic secondary amine and ferriporphyrin catalysts to carry out trifluoroethylation reaction to obtain a trifluoroethylated aromatic secondary amine compound; the two-step reaction is carried out by a one-pot method under mild conditions, no intermediate product is required to be separated, the reaction steps are few, the operation is simple, the substrate application range is wide, the raw material source is wide, and the yield of the reaction product is high.

Description

Method for catalyzing aromatic secondary amine trifluoroethylation by ferriporphyrin
Technical Field
The invention relates to a method for catalyzing aromatic secondary amine trifluoroethylation by ferriporphyrin, in particular to a method for generating a trifluoroethylated aromatic secondary amine compound by diazotizing trifluoroethylamine and substituting aromatic secondary amine; belonging to the field of organic intermediate synthesis.
Background
N-trifluoroethylated aromatic amine is a chemical with biological activity and widely applied to the fields of medicine and agricultural chemistry. The construction of N-trifluoroethylated aromatic amines has been an interesting research direction, and a large number of documents report the synthesis of N-trifluoroethylated aromatic amines. There are currently mainly two methods of constructing N-trifluoroethylated aromatic amines (Haghighi, F.; Panahi, F.; Golbon, M.H., Khalafine zhad. chem. Commun. 2017,53, 12650-S.1265), one using aryl halides coupled with 2,2, 2-trifluoroethylamine, and the second using N-H insertion of aromatic amines with different trifluoroethylating agents, such as 2,2, 2-trifluorodiazoethane, etc. However, these methods all suffer from the following drawbacks to varying degrees: 1. the reaction temperature is high (250 ℃), and the tolerance of the substrate functional group is poor; a noble metal catalyst such as a metallic palladium catalyst is required; the trifluorodiazonium salt needs to be isolated; only for primary amines, not for secondary amines.
Disclosure of Invention
Aiming at the defects of the method for introducing 2,2, 2-trifluoroethyl to the nitrogen atom of an amine compound in the prior art, the invention aims to provide the method for obtaining the trifluoroethylated aromatic secondary amine compound by a one-pot reaction under mild conditions at high yield, compared with the prior art, the method has the advantages of mild reaction conditions, avoidance of the use of noble metal or heavy metal catalysts, no need of separation of intermediate products through in-situ one-pot reaction, simpler operation and short flow, particularly, the method can introduce 2,2, 2-trifluoroethyl to the secondary amine, and overcomes the defect that the prior art is only suitable for introducing 2,2, 2-trifluoroethyl to primary amine.
In order to realize the technical purpose, the invention provides a method for catalyzing aromatic secondary amine trifluoroethylation by ferriporphyrin, which comprises the steps of firstly adding trifluoroethylamine salt and nitrite to carry out diazotization reaction in an acidic solution system, and then adding aromatic secondary amine and ferriporphyrin catalysts to carry out trifluoroethylation reaction to obtain a trifluoroethylated aromatic secondary amine compound;
the secondary aromatic amine has the structure of formula 1:
Figure BDA0001729497850000021
the trifluoroethylated aromatic secondary amine compound has the structure of formula 2:
Figure BDA0001729497850000022
wherein the content of the first and second substances,
R1and R2Independently selected from hydrogen, halogen substituent, aliphatic alkyl, alkoxy, alkylthio, aromatic alkyl or heterocyclic radical;
R3selected from alkyl groups.
In the technical scheme of the invention, the aryl of the aromatic secondary amine is mainly aromaticTo be phenyl or substituted phenyl, the number of substituents can be 1 or 2 (R)1And R2) The position of the substituent is not limited, and can be ortho-position, meta-position or para-position of the amino. The substituents can be selected from hydrogen or other inert substituents, which are generally substituents free of active hydrogen protons, such as halogen substituents, aliphatic alkyl groups, alkoxy groups, alkylthio groups, aromatic alkyl groups, heterocyclic groups, or the like. The halogen comprises chlorine, bromine or iodine, and the aromatic secondary amine substituted by chlorine, bromine and iodine has higher reactivity in the process of the trifluoroacetylation reaction. The aliphatic hydrocarbon group includes saturated aliphatic hydrocarbon group and unsaturated aliphatic hydrocarbon group, preferably C1～C6The alkyl group of (2) may be a straight-chain alkyl group or a branched-chain alkyl group. Alkoxy radicals comprising C1～C6The alkoxy group of (2) may be a straight-chain or branched alkyl group. Alkylthio radicals including C1～C6The alkyl group in the alkylthio group may be a straight-chain alkyl group or a branched-chain alkyl group. The aromatic hydrocarbon group includes a phenyl group or a substituted phenyl group, and also, the substituted phenyl group may have one or two substituents such as a halogen substituent, an aliphatic hydrocarbon group, an alkoxy group, an alkylthio group, and the like. Heterocyclyl includes thienyl or furyl. The most preferred aromatic secondary amines include N-methylaniline, N, 3-dimethylaniline, 3-chloro-N-methylaniline, N, 4-dimethylaniline, 4-chloro-N-methylaniline, 4-bromo-N-methylaniline, 4-methoxy-N-methylaniline. The substituents on the benzene ring have an influence on the activity of the trifluoroacetylation reaction. When the benzene ring contains an electron-donating substituent group, the activity of the trifluoroethylation reaction can be improved, and relatively high yield can be obtained, such as alkoxy, methyl and other electron-donating substituent groups, and particularly when the ortho-para position contains two electron-donating substituent groups simultaneously, higher yield can be obtained; if the benzene ring contains an electron withdrawing substituent, the activity of the trifluoroethylation reaction is reduced relative to the benzene ring, and relatively low yield is obtained, such as a chlorine substituent.
In the technical scheme of the invention, the substituent group on the N atom of the aromatic secondary amine is influenced by electronic effect and steric effect to limit the selection range, R3Preferably, C is selected1～C5Such as methyl, ethyl, isopropyl, etc.
In a preferable scheme, the molar ratio of the trifluoroethylamine salt to the nitrite is 1: 0.2-0.5.
Preferably, the molar ratio of the trifluoroethylamine salt to the aromatic secondary amine is 1: 0.1-0.2.
In a preferable scheme, the molar ratio of the aromatic secondary amine to the iron porphyrin catalyst is 1000: 3-15.
More preferably, the nitrite comprises sodium nitrite.
In a more preferred embodiment, the trifluoroethylamine salt is trifluoroethylamine hydrochloride.
In a preferable scheme, the ferriporphyrin catalyst comprises a monoferriporphyrin catalyst shown in a formula 3 and/or a 4 mu-oxybiferroporphyrin catalyst, and/or a solid catalyst formed by loading the monoferriporphyrin catalyst and/or the mu-oxybiferroporphyrin catalyst on an organic or inorganic carrier;
Figure BDA0001729497850000031
Figure BDA0001729497850000041
wherein the content of the first and second substances,
R1、R2and R3Independently selected from hydrogen, hydroxy, nitro, trifluoromethyl, halogen substituents, hydrocarbyl, alkoxy, cyano, amino, pyridyl, methylpyridyl, carboxy, sulfonic acid, cyclodextrin groups or calixarene groups;
l is selected from hydroxide radical, nitrate radical, trifluoro sulfonate radical, perchlorate radical, halide ion, acetate radical, carbonyl ligand, pyridine ligand or imidazole ligand.
R in the ferriporphyrin catalyst of formula 3 or formula 41、R2And R3When selected from halogen substituents, the halogen substituents can be fluorine, chlorine, bromine or iodine; r1、R2And R3When selected from hydrocarbon radicalsPreferably selected from alkyl radicals, e.g. C1～C5Typical alkyl groups such as methyl, ethyl, isopropyl, etc.; r1、R2And R3When selected from alkoxy, the alkoxy is C1～C5Alkoxy group of (2).
R in the iron porphyrin catalysts of formula 3 and formula 4 of the invention1、R2And R3The selection of (A) has no great influence on the catalytic effect and has equivalent effect.
In a preferred embodiment, the acidic solution system is a water/organic solvent mixed solution system containing an organic acid and/or an inorganic acid.
More preferably, the organic acid comprises formic acid and/or acetic acid. Acetic acid is preferred.
More preferably, the inorganic acid comprises hydrochloric acid and/or sulfuric acid. Dilute hydrochloric acid or dilute sulfuric acid is used.
In a preferred embodiment, the organic solvent includes at least one of dichloromethane and 1, 2-dichloroethane. 1, 2-dichloroethane is preferred.
In a preferable scheme, the volume ratio of water to the organic solvent in the acidic solution system is 1: 0.5-1.5.
In a preferred embodiment, the diazotization reaction conditions are as follows: reacting for 0.3-2 h at-10-40 ℃.
In a preferred embodiment, the trifluoroethylation conditions are: reacting for 8-24 h at 40-80 ℃.
After the trifluoroacetylation reaction is finished, a product is separated and purified by adopting a column chromatography method, wherein an eluent adopted by the column chromatography is a mixed solvent of petroleum ether and acetone, and the volume ratio of the petroleum ether to the acetone is 100: 1.
The reaction equation involved in the invention is as follows:
Figure BDA0001729497850000051
compared with the prior art, the technical scheme of the invention has the beneficial technical effects that:
1) in the synthesis process of the trifluoroethylated aromatic secondary amine compound, two steps of reactions are carried out at a lower temperature, the reaction conditions are mild, and the method has obvious technical advantages compared with the existing high-temperature synthesis method.
2) The method for synthesizing the trifluoroethylated aromatic secondary amine compound has the advantage of high yield, and the yield of a series of compounds is 45-93%.
3) The synthesis process of the trifluoroethylated aromatic secondary amine compound provided by the invention is carried out by a one-pot reaction, no intermediate product needs to be separated, the reaction steps are few, and the operation is simple.
4) The method for synthesizing the trifluoroethylated aromatic secondary amine compound has wide substrate application range, can obtain various trifluoroethylated aromatic secondary amine compounds, and has wide raw material sources and low cost.
5) The synthesis method of the trifluoroethylated aromatic secondary amine compound is green, environment-friendly and beneficial to industrial production.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of 4-methoxy-N-methyl-N- (2,2, 2-trifluoroethyl) aniline.
FIG. 2 is a nuclear magnetic carbon spectrum of 4-methoxy-N-methyl-N- (2,2, 2-trifluoroethyl) aniline.
Detailed Description
The present invention is further described in detail with reference to specific examples, but the embodiments of the present invention are not limited thereto, and may be performed with reference to conventional techniques for process parameters not particularly noted.
Example 1
Synthesis of N-methyl-N- (2,2, 2-trifluoroethyl) aniline
2mmol of trifluoroethylamine hydrochloride, 1mL of water, 34uL of acetic acid and 1mL of dichloroethane were added to the reaction tube, and a rubber stopper was fitted and fixed to the stirrer. 42mg of sodium nitrite is put into a 1.5mL sample tube, 1mL of water is added into the sample tube, and the sample tube is shaken to dissolve the sodium nitrite. The dissolved sodium nitrite solution was added dropwise to the reaction tube using a syringe and stirred continuously at room temperature for half an hour. TPPFeCl (catalytic amount, 9/1000 as molar amount of secondary amine) was dissolved in 1mL of dichloroethane, and 0.24mmol of N-methylaniline was taken in a sample tube. And after half an hour, dropwise adding the mixed solution in the sample tube into the reaction tube while stirring, and heating to 80 ℃ for reaction for 12 hours. Cooling the reaction liquid to room temperature, filtering to remove part of impurities, concentrating, and purifying by column chromatography to obtain the target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and acetone. The structure of the N-methyl-N- (2,2, 2-trifluoroethyl) aniline is shown as the following formula:
Figure BDA0001729497850000061
the compound is a light yellow liquid with a yield of 80%, and the nuclear magnetic data are as follows:
1H NMR(400MHz,CDCl3)δ7.19(d,J＝4.5Hz,2H),6.75(t,J＝6.9Hz,3H), 3.79(q,J＝8.9Hz,2H),2.98(s,3H).13C NMR(100MHz,CDCl3)δ＝148.7,130.0,125.6(q,J＝281.0Hz),118.3,112.7,54.4(q,J＝32.0Hz),39.2.19F NMR (377MHz,CDCl3)δ-70.49(t,J＝8.9Hz).
control experimental group:
the following control experimental group was mainly examined with respect to the conditions of the trifluoroethylation reaction of the secondary amine, such as the amount of nitrite, the kind of catalyst, the kind of acid, the kind of solvent, the reaction time and temperature, and the like. A condition optimization experiment was performed by taking the reaction of trifluoroethylamine hydrochloride and N-methylaniline as an example, and the specific reaction process was as in example 1.
1) Amount of sodium nitrite
In the reaction system, sodium nitrite is used as the nitrogen source indispensable for generating trifluoromethyl diazomethane in situ by using trifluoroethylamine hydrochloride, the added amount of sodium nitrite also has an important influence on the reaction, other conditions are kept the same as example 1, and the influence of the added amount of sodium nitrite on the reaction is examined, and the results are shown in table 1.
TABLE 1 different NaNO2Results at dose
Figure BDA0001729497850000062
As can be seen from table 1: when the amount of sodium nitrite added was 2eq, the yield of the trifluoroethylated product was 68%; when the amount of sodium nitrite added was 2.5eq, the yield of the trifluoroethylated product was 80%; when the amount of sodium nitrite added was 3eq, the trifluoroethylated product was 81%. It is shown that the amount of the product increases with the increase of sodium nitrite, but the amount of the product increase is not obvious later with the increase of sodium nitrite. When the amount of sodium nitrite is 2.5eq, the optimum amount is used.
2) Influence of the type of catalyst
The effect of the selection of the type of catalyst on the reaction was examined, keeping the other conditions the same as in example 1, and the results are shown in Table 2.
TABLE 2 reaction results for different catalysts
Figure BDA0001729497850000071
As can be seen from Table 2, only the ferriporphyrin-based catalysts, such as TPPFeCl or (TPPFe)2O and the like have good catalytic effect on the trifluoroethylation reaction of aromatic secondary amine, and other iron salt catalysts or cobalt, manganese, nickel and other metalloporphyrin compounds have no catalytic activity.
3) Kind of acid
The reaction was examined for the effect of the acid species on the reaction, while keeping the conditions the same as in example 1, and the results are shown in Table 3.
TABLE 3 results of the reactions of different types of acids
Figure BDA0001729497850000072
Figure BDA0001729497850000081
Using weak acids HCOOH and CH3COOH, the effect of the reaction is remarkableUsing strong acids HCl and H2SO4Good results are obtained. Since the acid acts to react with the sodium nitrite and then with the trifluoroethylamine hydrochloride to generate the diazonium salt in situ, the strong acid may not continue to react with the trifluoroethylamine hydrochloride due to the violent reaction rate with the sodium nitrite. And for two weak acids, CH3COOH was found to be somewhat more effective than HCOOH.
4) Kind of solvent
In the organic reaction, the solvent greatly influenced the reaction, and the influence of the organic solvent on the reaction was examined while keeping the other conditions the same as in example 1, and the results are shown in Table 4.
TABLE 4 reaction results for different solvents
Figure BDA0001729497850000082
According to the experimental results, the reaction is carried out at H2O:CH2ClCH2Cl and H2O:CH2Cl2All systems can react in H2O:DMSO、H2O Toluene and H2Almost no product is generated in the O-hexane system, and the main reason is that DMSO, Toluene and n-hexane are non-benign solvents of iron porphyrin, so that the catalyst does not play a catalytic role, and almost no reaction occurs. The solvency of dichloromethane for metalloporphyrin is the best, the solubility of 1, 2-dichloroethane for ferriporphyrin is the second best, H at room temperature2O:CH2Cl2And H2O:CH2ClCH2The yields of the two systems of Cl are respectively 40% and 37%. However, the boiling point of dichloromethane is too low, and H is selected for the convenience of increasing the temperature later to improve the reaction yield2O:CH2ClCH2A Cl solvent system.
5) Optimization of reaction temperature
The reaction was examined for the effect of the temperature of the trifluoroethylation reaction, keeping the other conditions the same as in example 1, and the temperature range mainly examined was from 40 ℃ to 80 ℃ based on the boiling point of 1, 2-dichloroethane of about 80 ℃, see table 5.
TABLE 5 results of the reactions at different temperatures
Figure BDA0001729497850000091
According to the experimental result, the higher the temperature is, the more beneficial the trifluoroethylation reaction of the secondary amine is, and when the temperature is 40 ℃, the trifluoroethylation yield of the aromatic secondary amine is 40%; the trifluoroethylation yield of the aromatic secondary amine was 57% at a temperature of 60 ℃; the yield of the trifluoroethylation of the aromatic secondary amine was 80% at a temperature of 80 ℃. However, the temperature at which the yield is highest can only be selected to be 80 ℃ since the maximum temperature has already reached the boiling point of the organic solvent.
6) Optimization of reaction time
The reaction time also has a great influence on the reaction result. The reaction time in the first step is half an hour in order to ensure the formation of trifluoromethyl diazomethane. The effect of the change in the reaction time of the second step on the yield of the product of the trifluoroacetylation reaction was examined while keeping the other conditions the same as in example 1, and is shown in Table 6.
TABLE 6 results of the reactions at different reaction times
Figure BDA0001729497850000092
From the experimental results it can be seen that the longer the reaction time of the second step, the higher the yield of the product of the trifluoroethylation, and that at 6h the yield of the product is only 55%. When the reaction time was increased to 12 hours, the yield of the product increased to 80% but when the reaction time of the second step was increased to 14 hours, the reaction tended to stabilize with little increase in yield. And 12h is the optimal reaction time in combination.
Example 2
Synthesis of 4-methoxy-N-methyl-N- (2,2, 2-trifluoroethyl) aniline
2mmol of trifluoroethylamine hydrochloride, 1mL of water, 34uL of acetic acid and 1mL of dichloroethane were added to the reaction tube, and a rubber stopper was fitted and fixed to the stirrer. 42mg of sodium nitrite was taken in 1.In a 5mL sample tube, 1mL of water was added to the sample tube, and the sample tube was shaken to dissolve the sodium nitrite. The dissolved sodium nitrite solution was added dropwise to the reaction tube using a syringe and stirred continuously at room temperature for half an hour. Dissolving iron porphyrin (R) of formula 3 with 1mL of dichloromethane2＝R3＝H，R1Cl ═ Cl, L ═ Cl) (catalytic amount, 9/1000, molar amount of secondary amine), 0.24mmol of 4-methoxy-N-methylaniline was taken in a sample tube. And after half an hour, dropwise adding the mixed solution in the sample tube into the reaction tube while stirring, and heating to 80 ℃ for reaction for 12 hours. Cooling the reaction liquid to room temperature, filtering to remove part of impurities, concentrating, and purifying by column chromatography to obtain the target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and acetone. The structure of the 4-methoxy-N-methyl-N- (2,2, 2-trifluoroethyl) aniline is shown as the following formula:
Figure BDA0001729497850000101
the compound was a pale yellow liquid with a yield of 75% and the nuclear magnetic data as follows:
1H NMR(400MHz,CDCl3)δ6.77(d,J＝8.8Hz,2H),6.70(d,J＝8.3Hz,2H), 3.74-3.64(m,5H),2.92(s,3H).13C NMR(100MHz,CDCl3)δ＝151.7,142.4,123.7(q, J＝281.0Hz),113.7,54.6(q,J＝32.0Hz),54.7,38.6.19F NMR(377MHz,CDCl3)δ -77.53(t,J＝9.0Hz).
example 3
Synthesis of N, 4-dimethyl-N- (2,2, 2-trifluoroethyl) aniline
2mmol of trifluoroethylamine hydrochloride, 1mL of water, 34uL of acetic acid and 1mL of dichloroethane were added to the reaction tube, and a rubber stopper was fitted and fixed to the stirrer. 42mg of sodium nitrite is put into a 1.5mL sample tube, 1mL of water is added into the sample tube, and the sample tube is shaken to dissolve the sodium nitrite. The dissolved sodium nitrite solution was added dropwise to the reaction tube using a syringe and stirred continuously at room temperature for half an hour. Dissolving iron porphyrin (R) of formula 3 with 1mL of dichloromethane1＝H，R2＝R3＝CF3L ═ OAc) (catalysis)Amount, 9/1000 as molar amount of secondary amine), 0.24mmol of N, 4-dimethylaniline was taken in a sample tube. And after half an hour, dropwise adding the mixed solution in the sample tube into the reaction tube while stirring, and heating to 80 ℃ for reaction for 12 hours. Cooling the reaction liquid to room temperature, filtering to remove part of impurities, concentrating, and purifying by column chromatography to obtain the target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and acetone. The structure of N, 4-dimethyl-N- (2,2, 2-trifluoroethyl) aniline is shown as the following formula:
Figure BDA0001729497850000111
the compound was a pale yellow liquid with 73% yield and the nuclear magnetic data were as follows:
1H NMR(400MHz,CDCl3)δ6.99(d,J＝7.9Hz,2H),6.65(d,J＝7.9Hz,2H), 3.74(q,J＝9.0Hz,2H),2.94(s,3H),2.19(s,3H).13C NMR(100MHz,CDCl3) δ＝145.6,128.7,126.5,124.6(q,J＝281.0Hz),112.0,53.7(q,J＝32.0Hz),38.2,19.2. 19F NMR(377MHz,CDCl3)δ-70.46(t,J＝9.0Hz).
example 4
Synthesis of N, 3-dimethyl-N- (2,2, 2-trifluoroethyl) aniline
2mmol of trifluoroethylamine hydrochloride, 1mL of water, 34uL of acetic acid and 1mL of dichloroethane were added to the reaction tube, and a rubber stopper was fitted and fixed to the stirrer. 42mg of sodium nitrite is put into a 1.5mL sample tube, 1mL of water is added into the sample tube, and the sample tube is shaken to dissolve the sodium nitrite. The dissolved sodium nitrite solution was added dropwise to the reaction tube using a syringe and stirred continuously at room temperature for half an hour. Dissolving iron porphyrin (R) of formula 4 with 1mL of dichloromethane1＝H，R2＝R3COOH) (catalytic amount, 9/1000 for secondary amine molar amount), 0.24mmol of N, 3-dimethylaniline was taken in a sample tube. And after half an hour, dropwise adding the mixed solution in the sample tube into the reaction tube while stirring, and heating to 80 ℃ for reaction for 12 hours. Cooling the reaction liquid to room temperature, filtering to remove part of impurities, concentrating, and purifying by column chromatography to obtain target productThe eluent of column chromatography is the mixed solvent of petroleum ether and acetone. The structure of the N, 3-dimethyl-N- (2,2, 2-trifluoroethyl) aniline is shown as the following formula:
Figure BDA0001729497850000112
the compound was a pale yellow liquid with a yield of 72% and the nuclear magnetic data as follows:
1H NMR(400MHz,CDCl3)δ7.07(t,J＝8.2Hz,1H),6.56(d,J＝15.7Hz,3H), 3.75(q,J＝9.0Hz,2H),2.95(s,3H),2.25(s,3H).13C NMR(100MHz,CDCl3)δ 147.8,138.0,128.1,124.6(q,J＝281.0Hz),118.2,112.5,109.0,53.4(q,J＝32.0Hz), 38.1,20.8.19F NMR(376MHz,CDCl3)δ-70.45(t,J＝9.0Hz).
example 5
Synthesis of 4-chloro-N-methyl-N- (2,2, 2-trifluoroethyl) aniline
2mmol of trifluoroethylamine hydrochloride, 1mL of water, 34uL of acetic acid and 1mL of dichloroethane were added to the reaction tube, and a rubber stopper was fitted and fixed to the stirrer. 42mg of sodium nitrite is put into a 1.5mL sample tube, 1mL of water is added into the sample tube, and the sample tube is shaken to dissolve the sodium nitrite. The dissolved sodium nitrite solution was added dropwise to the reaction tube using a syringe and stirred continuously at room temperature for half an hour. Dissolving iron porphyrin (R) of formula 4 with 1mL of dichloromethane1＝SO3Na，R2＝R3H) (catalytic amount, 9/1000 for secondary amine molar amount), 0.24mmol of 4-chloro-N-methylaniline was taken in a sample tube. And after half an hour, dropwise adding the mixed solution in the sample tube into the reaction tube while stirring, and heating to 80 ℃ for reaction for 12 hours. Cooling the reaction liquid to room temperature, filtering to remove part of impurities, concentrating, and purifying by column chromatography to obtain the target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and acetone. The structure of the 4-chloro-N-methyl-N- (2,2, 2-trifluoroethyl) aniline is shown as the following formula:
Figure BDA0001729497850000121
the compound was a pale yellow liquid with a yield of 70%, and its nuclear magnetic data were as follows:
1H NMR(400MHz,CDCl3)δ7.12(d,J＝7.9Hz,2H),6.63(d,J＝8.2Hz,2H), 3.74(q,J＝8.9Hz,2H),2.94(s,3H).13C NMR(100MHz,CDCl3)δ146.2,128.0, 124.4(q,J＝281.0Hz),122.2,112.9,53.3(q,J＝33.0Hz),38.3.19F NMR(377MHz, CDCl3)δ-70.42(t,J＝8.9Hz).
example 6
Synthesis of 4-bromo-N-methyl-N- (2,2, 2-trifluoroethyl) aniline
2mmol of trifluoroethylamine hydrochloride, 1mL of water, 34uL of acetic acid and 1mL of dichloroethane were added to the reaction tube, and a rubber stopper was fitted and fixed to the stirrer. 42mg of sodium nitrite is put into a 1.5mL sample tube, 1mL of water is added into the sample tube, and the sample tube is shaken to dissolve the sodium nitrite. The dissolved sodium nitrite solution was added dropwise to the reaction tube using a syringe and stirred continuously at room temperature for half an hour. Dissolving iron porphyrin (R) of formula 3 with 1mL of dichloromethane1As calixarenes, R2＝R3CN, L ═ OAc) (catalytic amount, 9/1000, molar amount of secondary amine), 0.24mmol of 4-bromo-N-methylaniline was taken in a sample tube. And after half an hour, dropwise adding the mixed solution in the sample tube into the reaction tube while stirring, and heating to 80 ℃ for reaction for 12 hours. Cooling the reaction liquid to room temperature, filtering to remove part of impurities, concentrating, and purifying by column chromatography to obtain the target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and acetone. The structure of the 4-bromo-N-methyl-N- (2,2, 2-trifluoroethyl) aniline is shown as the following formula:
Figure BDA0001729497850000131
the compound was a pale yellow liquid with 73% yield and the nuclear magnetic data were as follows:
1H NMR(400MHz,CDCl3)δ7.25(d,J＝8.2Hz,2H),6.58(d,J＝8.3Hz,2H), 3.75(q,J＝8.7Hz,2H),2.94(s,3H).13C NMR(100MHz,CDCl3)δ147.6,131.9, 125.4(q,J＝281.0Hz),114.4,110.4,54.2(q,J＝32.0Hz),39.3.19F NMR(377MHz, CDCl3)δ-70.37(t,J＝8.8Hz).
example 7
Synthesis of 3-chloro-N-methyl-N- (2,2, 2-trifluoroethyl) aniline
2mmol of trifluoroethylamine hydrochloride, 1mL of water, 34uL of acetic acid and 1mL of dichloroethane were added to the reaction tube, and a rubber stopper was attached and fixed to a stirrer. 42mg of sodium nitrite is put into a 1.5mL sample tube, 1mL of water is added into the sample tube, and the sample tube is shaken to dissolve the sodium nitrite. The dissolved sodium nitrite solution was added dropwise to the reaction tube using a syringe and stirred continuously at room temperature for half an hour. Dissolving iron porphyrin (R) of formula 4 with 1mL of dichloromethane1＝CF3，R2＝R3H) (catalytic amount, 9/1000 for secondary amine molar amount), 0.24mmol of 3-chloro-N-methylaniline was taken in a sample tube. And after half an hour, dropwise adding the mixed solution in the sample tube into the reaction tube while stirring, and heating to 80 ℃ for reaction for 12 hours. Cooling the reaction liquid to room temperature, filtering to remove part of impurities, concentrating, and purifying by column chromatography to obtain the target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and acetone. The structure of the 3-chloro-N-methyl-N- (2,2, 2-trifluoroethyl) aniline is shown as the following formula:
Figure BDA0001729497850000132
the compound was a pale yellow liquid with a yield of 72% and the nuclear magnetic data as follows:
1H NMR(400MHz,CDCl3)δ7.08(t,J＝8.1Hz,1H),6.70(d,J＝9.0Hz,2H), 6.59(d,J＝8.5Hz,1H),3.76(q,J＝8.8Hz,2H),2.96(s,3H).13C NMR(100MHz, CDCl3)δ＝148.7,134.2,129.1,124.3(q,J＝281.0 Hz),117.2,111.7,109.8,53.0(q,J＝33.0 Hz),38.2.19F NMR(377 MHz,CDCl3)δ-70.39(t,J＝8.8 Hz)。

Claims (7)

1. a method for catalyzing aromatic secondary amine trifluoroethylation by ferriporphyrin is characterized in that: in an acid solution system, firstly adding 2,2, 2-trifluoroethylamine salt and nitrite to carry out diazotization reaction, and then adding aromatic secondary amine and ferriporphyrin catalyst to carry out trifluoroethylation reaction to obtain a trifluoroethylated aromatic secondary amine compound;
the secondary aromatic amine has the structure of formula 1:
Figure DEST_PATH_IMAGE002
formula 1
The trifluoroethylated aromatic secondary amine compound has the structure of formula 2:
Figure DEST_PATH_IMAGE004
formula 2
Wherein the content of the first and second substances,
R1and R2Independently selected from hydrogen, chlorine substituent, bromine substituent, iodine substituent, C1~C6Alkyl of (C)1~C6Alkoxy group of (C)1~C6Alkylthio, phenyl, thienyl or furyl of;
R3is selected from C1~C5Alkyl groups of (a);
the ferriporphyrin catalyst is a monoferriporphyrin catalyst shown in a formula 3 and/or a 4 mu-oxyferriporphyrin catalyst, and/or a solid catalyst formed by loading the monoferriporphyrin catalyst shown in the formula 3 and/or the 4 mu-oxyferriporphyrin catalyst on an organic or inorganic carrier;
Figure DEST_PATH_IMAGE006
formula 3
Figure DEST_PATH_IMAGE008
Formula 4
Wherein the content of the first and second substances,
R1、R2and R3Independently selected from hydrogen, hydroxy, nitro, trifluoromethyl, halogen substituents, C1~C5Alkyl of (A), C1~C5Alkoxy, cyano, amino, pyridyl, methylpyridyl, carboxyl or sulfonic acid group;
l is selected from hydroxide, nitrate, trifluoro sulfonate, perchlorate, halide or acetate;
the acidic solution system is a water/organic solvent mixed solution system containing organic acid and/or inorganic acid; the organic acid is formic acid and/or acetic acid; the inorganic acid is hydrochloric acid and/or sulfuric acid; the organic solvent is at least one of dichloromethane and 1, 2-dichloroethane.
2. The method for catalyzing trifluoroethylation of aromatic secondary amine by ferriporphyrin according to claim 1, wherein: the aromatic secondary amine isN-methylaniline,N3-dimethylaniline, 3-chloro-N-methylaniline,N4-dimethylaniline, 4-chloro-N-methylaniline, 4-bromo-N-methylaniline or 4-methoxy-N-methylaniline.
3. The method for catalyzing trifluoroethylation of aromatic secondary amine by ferriporphyrin according to claim 1, wherein:
the molar ratio of the 2,2, 2-trifluoroethylamine salt to the nitrite is 1: 0.2-0.5;
the molar ratio of the 2,2, 2-trifluoroethylamine salt to the aromatic secondary amine is 1: 0.1-0.2;
the molar ratio of the aromatic secondary amine to the metalloporphyrin catalyst is 1000: 3-15.
4. The method for catalyzing trifluoroethylation of aromatic secondary amine by ferriporphyrin according to claim 2, wherein:
the nitrite is sodium nitrite;
the 2,2, 2-trifluoroethylamine salt is 2,2, 2-trifluoroethylamine hydrochloride.
5. The method for catalyzing trifluoroethylation of aromatic secondary amine by ferriporphyrin according to claim 1, wherein: the volume ratio of water to the organic solvent in the acidic solution system is 1: 0.5-1.5.
6. A process according to any one of claims 1,2, 3 and 5, wherein the ferriporphyrin is used for the trifluoroethylation of an aromatic secondary amine, and the process comprises: the diazotization reaction conditions are as follows: reacting for 0.3-2 h at-10-40 ℃.
7. A process according to any one of claims 1,2, 3 and 5, wherein the ferriporphyrin is used for the trifluoroethylation of an aromatic secondary amine, and the process comprises: the conditions of the trifluoroethylation are as follows: reacting for 8-24 h at 40-80 ℃.
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