CN113214158A - Preparation method of 2-trifluoromethyl imidazoline compound - Google Patents
Preparation method of 2-trifluoromethyl imidazoline compound Download PDFInfo
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- CN113214158A CN113214158A CN202110644644.4A CN202110644644A CN113214158A CN 113214158 A CN113214158 A CN 113214158A CN 202110644644 A CN202110644644 A CN 202110644644A CN 113214158 A CN113214158 A CN 113214158A
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- -1 2-trifluoromethyl imidazoline compound Chemical class 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 claims abstract description 30
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims abstract description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 12
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 239000002808 molecular sieve Substances 0.000 claims abstract description 6
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 239000000654 additive Substances 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- QJQYPZZUKLQGGT-UHFFFAOYSA-N methyl hypobromite Chemical compound COBr QJQYPZZUKLQGGT-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 abstract description 28
- 239000002994 raw material Substances 0.000 abstract description 7
- 150000002462 imidazolines Chemical class 0.000 abstract description 6
- 230000035484 reaction time Effects 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 2
- 229910001385 heavy metal Inorganic materials 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 30
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000004293 19F NMR spectroscopy Methods 0.000 description 5
- 238000004983 proton decoupled 13C NMR spectroscopy Methods 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 150000004982 aromatic amines Chemical class 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000005860 Heine reaction Methods 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- BWLHGYWAFIMGJI-GJZGRUSLSA-N (3S,6S)-3-[(3-fluoro-4-hydroxyphenyl)methyl]-6-[(4-hydroxyphenyl)methyl]piperazine-2,5-dione Chemical compound C1=CC(=CC=C1C[C@H]2C(=O)N[C@H](C(=O)N2)CC3=CC(=C(C=C3)O)F)O BWLHGYWAFIMGJI-GJZGRUSLSA-N 0.000 description 1
- AJVDOFRZQWMSLK-UHFFFAOYSA-N 2-(trifluoromethyl)-4,5-dihydro-1h-imidazole Chemical compound FC(F)(F)C1=NCCN1 AJVDOFRZQWMSLK-UHFFFAOYSA-N 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- MGFYSGNNHQQTJW-UHFFFAOYSA-N iodonium Chemical compound [IH2+] MGFYSGNNHQQTJW-UHFFFAOYSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a preparation method of a 2-trifluoromethyl imidazoline compound, which comprises the following steps: adding N-iodosuccinimide, a 4A molecular sieve, trifluoroethylimidoyl chloride and allyl amine into an organic solvent, reacting at room temperature for 1-2 hours completely, and performing post-treatment to obtain the 2-trifluoromethyl imidazoline compound. The preparation method is simple to operate, the initial raw materials are cheap and easy to obtain, the reaction conditions are mild, the reaction time is short, the reaction does not need to be operated under the anhydrous and anaerobic conditions, heavy metals are not used as catalysts, the reaction can be expanded to gram level, imidazoline compounds with trifluoromethyl groups, which are variously substituted at different positions, can be synthesized through substrate design, and the applicability of the method is expanded while the operation is convenient.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a 2-trifluoromethyl imidazoline compound.
Background
Imidazoline compounds are important five-membered nitrogen-containing heterocycles with a wide range of biological and pharmaceutical activities, such as anti-cancer, anti-inflammatory, anti-diabetic and anti-hypertensive activities (j.med.chem.2009,52,1302). Some imidazoline structures can also be used as synthesis intermediates, organic adjuvants, and chiral ligands (org. lett.2020,22,2868). Therefore, many synthetic methods have been developed to construct such important nitrogen-containing heterocyclic compounds.
The traditional methods for preparing imidazolines reported in the literature today are the Heine reaction and related methods derived from the Heine reaction. These methods have the disadvantages of various synthetic steps and low total reaction yield. In addition, efficient synthesis methods have not been widely reported for some specially functionalized imidazoline compounds, such as trifluoromethyl substituted imidazolines.
Based on the method, a method for synthesizing 2-trifluoromethyl imidazoline simply and efficiently by using allyl amine and trifluoroethylimidoyl chloride which are simple and easy to obtain as starting materials and performing iodo cyclization reaction promoted by N-iodo succinimide is developed.
Disclosure of Invention
The invention provides a preparation method of a 2-trifluoromethyl imidazoline compound, which has the advantages of simple steps, cheap and easily-obtained starting raw materials, mild reaction conditions, short reaction time, no need of anhydrous and anaerobic conditions, avoidance of the use of toxic heavy metal catalysts and convenience in operation and application; the reaction can be easily expanded to gram-scale reaction, and the iodomethyl in the product is easy to be subjected to derivatization, so that the possibility is provided for future large-scale production and application.
A preparation method of a 2-trifluoromethyl imidazoline compound comprises the following steps: adding N-iodosuccinimide, a 4A molecular sieve, trifluoroethylimidoyl chloride and allyl amine into an organic solvent, reacting at room temperature for 1-2 hours completely, and performing post-treatment to obtain the 2-trifluoromethyl imidazoline compound;
the structure of the trifluoroethylimidoyl chloride is shown as a formula (II):
the allyl amine has a structure shown in formula (III):
the structure of the 2-trifluoromethyl imidazoline compound is shown as the formula (I):
in formulae (I) to (III), R1Is a substituted or unsubstituted aryl group;
R2is H, C1～C4Alkyl, substituted or unsubstituted aryl;
at R1Wherein the substituents on the aryl group are selected from C1～C4Alkyl radical, C1～C4Alkoxy, halogen or trifluoromethyl.
The equivalent of the N-iodosuccinimide is 1-3 equivalents;
R1the substitution position of the upper aryl group can be ortho-position, para-position or meta-position.
The reaction formula is exemplified as follows:
during the reaction, firstly, the coupling reaction of trifluoroethylimidoyl chloride and allylamine is probably carried out to generate an amidine intermediate, then N-iodosuccinimide and a double bond are subjected to iodination reaction to obtain a ternary iodonium ion, and then intramolecular nucleophilic attack and deprotonation are carried out to obtain the final 2-trifluoromethyl imidazoline compound. The reaction may proceed by ionic processes.
In the present invention, the optional post-processing procedure includes: filtering, mixing the sample with silica gel, and finally performing column chromatography purification to obtain the corresponding 2-trifluoromethyl imidazoline compound, wherein the column chromatography purification is a technical means commonly used in the field.
Preferably, R1The substituted or unsubstituted phenyl is selected from methyl, methoxy, bromine or trifluoromethyl, and in this case, the aromatic amine and the trifluoroethylimidoyl chloride are easily obtained and the reaction yield is high.
Preferably, R2H, methyl, phenyl or naphthyl, in which case the allylamine is readily prepared and the reaction yields are high.
Preferably, the iodide is N-iodosuccinimide, which is used in the reaction at a high yield.
Preferably, the 4A molecular sieve is used as the additive, the molecular sieve is cheaper and commonly used, and the reaction yield is higher.
The allylamine is relatively easy to prepare, and is preferably used in excess of the p-trifluoroethylimidoyl chloride, and the molar ratio of trifluoroethylimidoyl chloride: allyl amine: n-iodosuccinimide is 1: 2-3: 1-3; as a further preference, the molar amount of trifluoroethylimidoyl chloride: allyl amine: n-iodosuccinimide ═ 1:2.5: 2.
In the present invention, the organic solvent capable of sufficiently dissolving the raw material can cause the reaction, but the difference in reaction efficiency is large, and the aprotic solvent is preferably an aprotic solvent which can effectively promote the reaction; preferably, the organic solvent is acetonitrile, DMSO or DMF; more preferably, the organic solvent is acetonitrile, in which case the starting materials are converted to the product in high conversion.
The amount of the organic solvent can be used for better dissolving the raw materials, and the amount of the organic solvent used for 1mmol of trifluoroethylimidoyl chloride is about 5-10 mL.
Preferably, the iodide is N-iodosuccinimide, and the reaction efficiency is high when the N-iodosuccinimide is used as an accelerator.
As a further preference, the 2-trifluoromethyl imidazoline compound is one of the compounds shown in the formula (I-1) and the formula (I-5):
in the preparation method, the aromatic amine, the individual allylamine and the N-iodosuccinimide are generally commercially available products and can be conveniently obtained from the market, and the trifluoroethylimidoyl chloride can be quickly synthesized from the corresponding aromatic amine, triphenylphosphine, carbon tetrachloride and trifluoroacetic acid.
Compared with the prior art, the invention has the beneficial effects that: the preparation method does not need anhydrous and anaerobic conditions, has room temperature reaction, high reaction efficiency, easy operation and simple and convenient post-treatment, and can expand the reaction to gram level; the reaction starting raw materials are cheap and easy to obtain, the designability of the reaction substrate is strong, the tolerance range of the substrate functional group is wide, different substituted imidazoline compounds can be designed and synthesized according to actual needs, and the practicability is strong.
Detailed Description
The invention is further described with reference to specific examples.
Examples 1 to 15
Adding N-iodosuccinimide, a 4A molecular sieve, trifluoroethylimidoyl chloride (II), allyl amine (III) and 2mL of an organic solvent into a 35mL Schlenk tube according to the raw material ratio of Table 1, mixing and stirring uniformly, reacting according to the reaction conditions of Table 2, filtering after the reaction is finished, mixing a sample with silica gel, and purifying by column chromatography to obtain a corresponding 2-trifluoromethyl imidazoline compound (I), wherein the reaction process is shown as the following formula:
TABLE 1 raw material addition amounts of examples 1 to 15
TABLE 2
In tables 1 and 2, T is the reaction temperature, T is the reaction time, Ph is phenyl, Me is methyl, SMe is methylthio, and T-Bu is tert-butyl.
Structure confirmation data of the compounds prepared in examples 1 to 5:
nuclear magnetic resonance of 2-trifluoromethylimidazoline Compound (I-1) prepared in example 1 (II-1)1H NMR、13C NMR and19f NMR) the data were:
1H NMR(400MHz,CDCl3)δ7.22(s,4H),4.15(d,J＝17.1Hz,1H),3.96(d,J＝17.1Hz,1H),3.28(d,J＝10.7Hz,1H),3.21(d,J＝10.7Hz,1H),2.40(s,3H),1.47(s,3H).
13C{1H}NMR(101MHz,CDCl3)δ152.6(C-F,q,2JC-F＝35.7Hz),139.5,131.0,130.1,129.9,117.2(C-F,q,1JC-F＝276.5Hz),67.8,65.4,24.6,21.1,15.8.
19F NMR(377MHz,CDCl3)δ-65.8.
M.p.112.4-113.5℃
HRMS(ESI):[M+H]+Calcd.for C13H14F3IN2 383.0227；Found 383.0236.
nuclear magnetic resonance of 2-trifluoromethylimidazoline Compound (I-2) prepared in example 2 ((II-2))1H NMR、13C NMR and19f NMR) the data were:
1H NMR(400MHz,CDCl3)δ7.32(s,1H),7.14(t,J＝8.2Hz,1H),4.17(d,J＝16.7Hz,1H),3.92(d,J＝16.5Hz,1H),3.24(q,J＝10.7Hz,1H),1.45(s,2H)
13C{1H}NMR(101MHz,CDCl3)δ162.7(C-F,d,1JC-F＝250.1Hz),152.1(C-F,q,2JC-F＝35.5Hz),152.2,151.9,132.4(C-F,d,3JC-F＝8.8Hz),130.4,117.4(C-F,q,1JC-F＝286.2Hz),117.2,116.2(C-F,q,2JC-F＝22.7Hz),67.4,66.7,24.6,15.7.
19F NMR(377MHz,CDCl3)δ-111.3,-65.8.
HRMS(ESI):[M+H]+Calcd.for C12H11F4IN2 386.9976；Found 386.9984.
nuclear magnetic resonance of 2-trifluoromethylimidazoline Compound (I-3) prepared in example 3 ((II-3))1H NMR、13C NMR and19f NMR) the data were:
1H NMR(400MHz,CDCl3)δ7.71(d,J＝8.4Hz,2H),7.44(d,J＝8.2Hz,2H),4.18(d,J＝17.8Hz,1H),3.93(d,J＝17.7Hz,1H),3.23(q,J＝10.8Hz,1H),1.45(s,3H).
13C{1H}NMR(101MHz,CDCl3)δ151.7(C-F,q,2JC-F＝35.7Hz),138.2,131.1(C-F,q,2JC-F＝33.0Hz),130.7,126.4,123.6(C-F,q,1JC-F＝272.3Hz),117.4(C-F,q,1JC-F＝275.7Hz),67.8,66.9,24.6,15.5.
19F NMR(377MHz,CDCl3)δ-62.7,-65.5.
M.p.102.4–104.3℃
HRMS(ESI):[M+H]+Calcd.for C13H11F6IN2 436.9944；Found 436.9950.
nuclear magnetic resonance of 2-trifluoromethylimidazoline Compound (I-4) prepared in example 4 (II)1H NMR、13C NMR and19f NMR) the data were:
1H NMR(400MHz,CDCl3)δ7.28–6.86(m,4H),4.12(d,J＝17.2Hz,1H),3.86(d,J＝20.6Hz,4H),3.25(d,J＝10.6Hz,1H),3.17(d,J＝10.5Hz,1H),1.41(s,3H).
13C{1H}NMR(101MHz,CDCl3)δ157.8(C-F,q,2JC-F＝37.3Hz),130.2,130.1,129.1,115.7(C-F,q,1JC-F＝287.7Hz),114.9,113.4,53.1,44.2,20.5,9.7.
19F NMR(377MHz,CDCl3)δ-75.6.
HRMS(ESI):[M+H]+Calcd.for C11H10F3IN2 369.0070；Found 369.0068.
nuclear magnetic resonance of 2-trifluoromethylimidazoline Compound (I-5) prepared in example 5 (II)1H NMR、13C NMR and19f NMR) the data were:
1H NMR(400MHz,CDCl3)δ7.44–7.17(m,5H),6.96(d,J＝8.1Hz,2H),6.68(d,J＝7.9Hz,2H),4.62(d,J＝17.9Hz,1H),4.46(d,J＝18.3Hz,1H),3.72(q,J＝10.6Hz,2H),2.27(s,3H).
13C{1H}NMR(101MHz,CDCl3)δ152.4(C-F,q,2JC-F＝35.3Hz),140.4,138.8,131.6,129.8,129.4,128.7,128.5,127.0,117.6(C-F,q,1JC-F＝275.7Hz),71.9,69.6,21.1,13.3.
19F NMR(377MHz,CDCl3)δ-65.5.
M.p.118.3–119.2℃.
HRMS(ESI):[M+H]+Calcd.for C18H16F3IN2 445.0383；Found 445.0390.
Claims (8)
1. a preparation method of a 2-trifluoromethyl imidazoline compound is characterized by comprising the following steps: adding an iodide, an additive, trifluoroethylimidoyl chloride and allyl amine into an organic solvent, reacting at room temperature for 1-2 hours, and performing post-treatment to obtain the 2-trifluoromethyl imidazoline compound;
the structure of the trifluoroethylimidoyl chloride is shown as a formula (II):
the allyl amine has a structure shown in formula (III):
the structure of the 2-trifluoromethyl imidazoline compound is shown as the formula (I):
in formulae (I) to (III), R1Is a substituted or unsubstituted aryl group;
R2is H, C1～C4Alkyl, substituted or unsubstituted aryl;
at R1Wherein the substituents on the aryl group are selected from C1～C4Alkyl radical, C1～C4Alkoxy radical, C1～C4Alkylthio, halogen or trifluoromethyl;
at R2In (1), the substituent on the aryl group is halogen.
2. The method for producing 2-trifluoromethylimidazoline compound according to claim 1, wherein R is1Is substituted or unsubstituted phenyl;
the substituent on the phenyl is selected from methyl, methoxy, bromine or trifluoromethyl.
3. The method for producing 2-trifluoromethylimidazoline compound according to claim 1, wherein R is2Is H, methyl, substituted or unsubstituted phenyl or naphthyl;
the substituent on the phenyl group is Cl.
4. The method for producing a 2-trifluoromethylimidazoline compound according to claim 1, wherein the molar amount of trifluoroethylimidoyl chloride: allyl amine: the iodide is 1:2 to 3:1 to 3.
5. The method for preparing 2-trifluoromethylimidazoline compound according to claim 1, wherein the organic solvent is acetonitrile.
6. The method for preparing 2-trifluoromethylimidazoline compound according to claim 1, wherein the iodide is N-iodosuccinimide.
7. The method for preparing 2-trifluoromethyl imidazoline compound according to claim 1, wherein the additive is 4A molecular sieve.
8. The method for preparing a 2-trifluoromethylimidazoline compound according to claim 1, wherein the 2-trifluoromethylimidazoline compound is one of compounds represented by formula (I-1) to formula (I-5):
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Non-Patent Citations (3)
| Title |
|---|
| ELHAM KAZEMI ET AL.: ""Intramolecular oxidative cyclization of N-(2,2,2-trifluoro-1-(phenylimino)ethyl)benzimidamide"", 《MOLECULAR DIVERSITY》 * |
| SHAN LI ET AL.: ""Iodine-mediated aminohalogenation-oxidation to synthesize 2-fluoroalkyl imidazole derivatives"", 《CHEMICAL PAPERS》 * |
| YUFEI SONG ET AL.: ""The cascade coupling/iodoaminocyclization reaction of trifluoroacetimidoyl chlorides and allylamines: metal-free access to 2-trifluoromethyl-imidazolines"", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 * |
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Application publication date: 20210806 |