CN110818541A - Preparation method of (E) -1-aryl-4, 4, 4-trifluorobutan-2-en-1-one compound - Google Patents
Preparation method of (E) -1-aryl-4, 4, 4-trifluorobutan-2-en-1-one compound Download PDFInfo
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Abstract
The invention discloses a preparation method of (E) -1-aryl-4, 4, 4-trifluorobutan-2-en-1-one compounds, belonging to the field of compound preparation. The (E) -1-aryl-4, 4, 4-trifluorobutan-2-ene-1-ketone takes a compound shown in a general formula II as a raw material, and reacts according to the following reaction formula in the presence of an oxidant and alkali to obtain the compound shown in the general formula I.
Description
Technical Field
The invention relates to a preparation method of (E) -1-aryl-4, 4, 4-trifluorobutan-2-en-1-one compounds, belonging to the field of compound preparation.
Background
It is well known that the introduction of CF into organic molecules is due to the special properties of the fluorine element3The physical, chemical and biological properties of the molecule can be significantly altered (chem. rev.2016, 116, 422). Therefore, the fluorine-containing compound has important application in the fields of medicine, agriculture, materials and the like. (E) The (E) -1-aryl-4, 4, 4-trifluorobut-2-en-1-one compound is an important reaction intermediate in organic synthesis reaction and an important building block for synthesizing a trifluoromethyl-containing compound, and can construct a novel trifluoromethyl-containing active molecule through various reactions. For example, it can be applied to michael addition reaction (org.lett.2017,19,5102), friedel-crafts reaction (chem.eur.j.2010,16,9117), diels-alder reaction (Tetrahedron 2018,74, 5232).
Currently, relatively few reports have been made on the synthesis of (E) -1-aryl-4, 4, 4-trifluorobut-2-en-1-one compounds. A common synthetic method is to obtain the compound by converting trifluoromethyl substituted propargyl alcohol (J.org.chem.2011,76,1957; org.Lett.2004,6,4073; Synlett2019,30,356). However, these methods use relatively expensive reagents and are harsh in reaction conditions, and sometimes use metal reagents, thereby greatly limiting the application of these methods.
Disclosure of Invention
The invention aims to provide a method for synthesizing (E) -1-aryl-4, 4, 4-trifluorobutan-2-en-1-one compounds (compounds shown in a general formula I) in one step, which has low cost and wide and easily obtained raw materials, directly uses 4-methylpyridine-N-oxide as an oxidant, uses triethylamine as a base, and uses trifluoromethyl substituted enol sulfonate (compounds shown in a general formula II) as a raw material, and is efficient, simple, convenient and economical.
A process for preparing (E) -1-aryl-4, 4, 4-trifluorobut-2-en-1-one compound includes such steps as reaction of the compound shown in general formula II in the presence of oxidant and alkali in solvent or in solvent under the condition of no solvent to obtain the compound shown in general formula I,
wherein the content of the first and second substances,
ar is selected from
Wherein X is selected from O, S, N (CH)3) (ii) a n is 1,2, 3,4 and 5, and the wavy line is a connecting position;
r is selected from H, C1-C6 alkyl, phenyl, halogen, trifluoromethyl, trifluoromethoxy, C1-C4 alkoxy, C2-C5 ester group or cyano;
the oxidant is one of pyridine-N-oxide, 2-chloro-pyridine-N-oxide, 2-methyl-pyridine-N-oxide, 4-nitro-pyridine-N-oxide, 4-methyl-pyridine-N-oxide, 2, 6-dichloro-pyridine-N-oxide and 2, 6-dimethyl-pyridine-N-oxide;
the alkali is one of triethylamine, pyrrolidine, 1, 8-diazabicycloundec-7-ene, 4-dimethylamino pyridine, tri-N-butylamine, tetramethyl ethylenediamine, diisopropylethylamine and N, N-dimethylbenzylamine.
The solvent is preferably one of tetrahydrofuran, 1, 2-dichloroethane, dichloromethane, chloroform, toluene, N-dimethylformamide and dimethyl sulfoxide;
the invention can also be carried out in the absence of a solvent;
the solvent of the invention can be used in an amount meeting the reaction requirement, and the ratio of the amount of the compound substance shown in the general formula II to the volume of the solvent is preferably 1mmol (5-15) mL.
Unless otherwise indicated, the terms used herein have the following meanings.
The term "alkyl" as used herein includes straight chain and branched chain alkyl groups. Reference to a single alkyl group, such as "methyl", is intended to refer only to straight chain alkyl groups, and reference to a single branched alkyl group, such as "isopropyl", is intended to refer only to branched alkyl groups. For example, "C4 lower alkyl" includes methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, and the like. Similar rules apply to other groups used in this specification.
The term "halogen" as used herein includes fluorine, chlorine, bromine, iodine.
The C2-C5 ester group is a group with the following structure: -COOR, wherein R is C1-C4 alkyl.
The C1-C4 alkoxy group is a group having the following structure: -O-M1Wherein M is1Is C1-C4 alkyl, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy.
In the above scheme, the
(n-1, 2,3,4, 5) and the position of the wavy line is a connecting position, wherein (R)nWhere n ═ 1,2, 3,4,5 means that the substitution of R on the phenyl group can be mono-or multi-substituted, and can be 1,2, 3,4 or 5 substituted. When n is 1, the substituent is monosubstituted, and the monosubstituted substituent can be 2,3 or 4; when n is 2,3,4 or 5, the substituent is multi-position substitution, wherein, n is 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3, 5-; n-3 is trisubstituted with the trisubstituted substitution positions being 2,3,4-, 2,3,5-, 2,3,6-, 3,4, 5-.
In the (E) -1-aryl-4, 4, 4-trifluorobut-2-en-1-one compound of the present invention, Ar is selected from the group consisting of
Wherein X is selected from O, S, N (CH)3)；n＝1、2、3、4、5；
R is selected from one of alkyl H, C1-C6, phenyl, halogen, trifluoromethyl, trifluoromethoxy and cyano; further, R is selected from one of H, methyl, isopropyl, phenyl, halogen, trifluoromethyl and cyano;
according to the preparation method of the (E) -1-aryl-4, 4, 4-trifluorobutan-2-en-1-one compound, the amount of the oxidant is 1.0-2.0 times of that of the compound shown in the general formula II;
in the method for preparing the (E) -1-aryl-4, 4, 4-trifluorobutan-2-en-1-one compound, the amount of the alkali substance is 0.2-1.0 time of that of the compound substance shown in the general formula II;
in the method for preparing the (E) -1-aryl-4, 4, 4-trifluorobutan-2-en-1-one compound, the reaction temperature of the reaction is preferably 15-25 ℃, and the reaction time is preferably 3-6 h. A preferred technical scheme of the invention is as follows:
a preparation method of (E) -1-aryl-4, 4, 4-trifluorobutan-2-en-1-one compounds takes compounds shown in a general formula II as raw materials, and the compounds are reacted according to the following reaction formula in a solvent or under the condition of no solvent in the presence of an oxidant and alkali to obtain the compounds shown in the general formula I, wherein the reaction temperature is 25 ℃, and the reaction time is 3 h-6 h.
Wherein the content of the first and second substances,
ar is selected fromWherein X is selected from O, S, N (CH)3)；n＝1、2、3、4、5；
R is selected from H, methyl, isopropyl, phenyl, halogen, trifluoromethyl, methoxy, carbethoxy or cyano;
the oxidant is one of pyridine-N-oxide, 2-chloro-pyridine-N-oxide, 2-methyl-pyridine-N-oxide, 4-nitro-pyridine-N-oxide, 4-methyl-pyridine-N-oxide, 2, 6-dichloro-pyridine-N-oxide and 2, 6-dimethyl-pyridine-N-oxide;
the alkali is one of triethylamine, pyrrolidine, 1, 8-diazabicycloundec-7-ene, 4-dimethylamino pyridine, tri-N-butylamine, tetramethylethylenediamine, diisopropylethylamine and N, N-dimethylbenzylamine;
the solvent is preferably one of tetrahydrofuran, 1, 2-dichloroethane, dichloromethane, chloroform, toluene, N-dimethylformamide and dimethyl sulfoxide;
the invention can also be carried out in the absence of a solvent;
specific structures of substituents of the respective raw material compounds in the above reaction formulae are listed in table 1. But is not limited to these structures.
TABLE 1
(Note: the position of the wavy line is a connection position)
Table 2 lists the structures, physical properties and properties of specific compounds 1 to 18 synthesized by the present invention1H NMR data, but the present invention is not limited to these compounds.
TABLE 2
Of the above products1H NMR data show that the coupling constant between CH and hydrogen on CH is 15-16, and the structure belongs to the (E) configuration.
The method directly uses cheap and commercially available pyridine-N-oxide as an oxidant, and provides a convenient and low-cost method for synthesizing the (E) -1-aryl-4, 4, 4-trifluorobutan-2-en-1-one compound. The method does not require the use of metal reagents, while avoiding the use of expensive trifluoromethylating reagents.
Detailed Description
The following non-limiting examples are presented to enable those of ordinary skill in the art to more fully understand the present invention and are not intended to limit the invention in any way.
The test methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
Example 1
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
To a 25mL Schlenk flask under protection of argon at room temperature were added 334mg (1.0mmol) of 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, 4mL of anhydrous solvent 1, 2-dichloroethane, 2.0 times the molar amount of 4-phenylpyridine-N-oxide, 218mg (2.0mmol) of 4-methylpyridine-N-oxide, 1, 1-trifluoro-2-butene, and 101mg (1.0mmol) of triethylamine, 1.0 times the molar amount of 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, in this order, and the mixture was allowed to react at 25 ℃ for 3 hours. After the solvent was removed by rotary evaporation under reduced pressure, the target compound was obtained by column chromatography with silica gel as the filler and petroleum ether as the eluent in 81% isolation yield.
Example 2
(E) Preparation of (E) -1- (4-methylphenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 2)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (4-methylphenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 84%.
Example 3
(E) Preparation of (E) -1- (3-methylphenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 3)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (3-methylphenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 82%.
Example 4
(E) Preparation of (E) -1- (2-methylphenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 4)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (2-methylphenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 78%.
Example 5
(E) Preparation of (E) -1- (4-isopropylphenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 5)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (4-isopropylphenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, and the isolation yield of the objective compound was 85%.
Example 6
(E) Preparation of (E) -1- (4-Biphenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 6)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (4-biphenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the objective compound in an isolation yield of 80%.
Example 7
(E) Preparation of (E) -1- (2-naphthyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 7)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (2-naphthyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 82%.
Example 8
(E) Preparation of (E) -1- (1-naphthyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 8)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (1-naphthyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the objective compound in an isolated yield of 73%.
Example 9
(E) Preparation of (E) -1- (4-bromophenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 9)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (4-bromophenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 84%.
Example 10
(E) Preparation of (E) -1- (4-fluorophenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 10)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (4-fluorophenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 85%.
Example 11
(E) Preparation of (E) -1- (4-chlorophenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 11)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (4-chlorophenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 86%.
Example 12
(E) Preparation of (E) -1- (3-chlorophenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 12)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (3-chlorophenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 86%.
Example 13
(E) Preparation of (E) -1- (2-chlorophenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 13)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (2-chlorophenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 80%.
Example 14
(E) Preparation of (E) -1- (2-trifluoromethylphenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 14)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (2-trifluoromethylphenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 81%.
Example 15
(E) Preparation of (E) -1- (4-cyanophenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 15)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (4-cyanophenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 87%.
Example 16
(E) Preparation of (E) -1- (3-chloro-2-fluorophenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 16)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (2-fluoro-3-chlorophenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 79%.
Example 17
(E) Preparation of (E) -1- (2-chloro-4-fluorophenyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 17)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 4- (2-chloro-4-fluorophenyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, whereby the isolation yield of the objective compound was 77%.
Example 18
(E) Preparation of (E) -1- (2-thienyl) -4,4, 4-trifluorobut-2-en-1-one (Compound 18)
The procedure was carried out in the same manner as in example 1 except for replacing 4-phenyl-2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene in example 1 with the same molar amount of 1- (2-thienyl) -2-trifluoromethanesulfonic acid group-1, 1, 1-trifluoro-2-butene, to obtain the desired compound in an isolated yield of 82%.
Example 19
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated except for using 2-chloropyridine-N-oxide as the 4-methylpyridine-N-oxide and dichloromethane as the 1, 2-dichloroethane in example 1 to obtain a hydrogen nuclear magnetic yield of the objective compound of 65% (using methyl terephthalate as an internal standard).
Example 20
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated except for using 2-methylpyridine-N-oxide as the 4-methylpyridine-N-oxide and dichloromethane as the 1, 2-dichloroethane in example 1 to obtain a hydrogen nuclear magnetic yield of the objective compound of 82% (using methyl terephthalate as an internal standard).
Example 21
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated except for using 4-methylpyridine-N-oxide and 1, 2-dichloroethane as 4-nitropyridine-N-oxide and dichloromethane in example 1 to obtain a hydrogen nuclear magnetic yield of 55% (based on methyl terephthalate as an internal standard) of the objective compound.
Example 22
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated except for using pyridine-N-oxide as the 4-methylpyridine-N-oxide and dichloromethane as the 1, 2-dichloroethane in example 1 to obtain a hydrogen nuclear magnetic yield of the objective compound of 84% (using methyl terephthalate as an internal standard).
Example 23
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that 4-methylpyridine-N-oxide was replaced with 2, 6-dichloropyridine-N-oxide and 1, 2-dichloroethane was replaced with dichloromethane, whereby a hydrogen nuclear magnetic yield of the objective compound (using methyl terephthalate as an internal standard) was 43%.
Example 24
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that 4-methylpyridine-N-oxide was replaced with 2, 6-dimethylpyridine-N-oxide and 1, 2-dichloroethane was replaced with dichloromethane, whereby 71% of the nuclear magnetic yield of the objective compound (using methyl terephthalate as an internal standard) was obtained.
Example 25
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated except that the amount of 4-methylpyridine-N-oxide in example 1 was changed to 1.0mmol and 1, 2-dichloroethane was changed to dichloromethane, to obtain a hydrogen nuclear magnetic yield of the objective compound of 57% (using methyl terephthalate as an internal standard).
Example 26
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that triethylamine in example 1 was replaced with pyrrolidine and 1, 2-dichloroethane was replaced with dichloromethane, whereby a hydrogen nuclear magnetic yield of the objective compound (based on methyl terephthalate as an internal standard) was obtained at 30%.
Example 27
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that triethylamine was replaced with 1, 8-diazabicycloundecen-7-ene and 1, 2-dichloroethane was replaced with dichloromethane, to obtain 29% of the target compound (internal standard methyl terephthalate).
Example 28
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that triethylamine in example 1 was replaced with 4-dimethylaminopyridine and 1, 2-dichloroethane was replaced with dichloromethane, whereby 47% of hydrogen nuclear magnetic yield of the objective compound (using methyl terephthalate as an internal standard) was obtained.
Example 29
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that triethylamine was replaced with tri-n-butylamine and 1, 2-dichloroethane was replaced with dichloromethane, whereby a hydrogen nuclear magnetic yield of the objective compound of 77% (using methyl terephthalate as an internal standard) was obtained.
Example 30
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that triethylamine in example 1 was replaced with tetramethylethylenediamine and 1, 2-dichloroethane was replaced with dichloromethane, whereby 78% of hydrogen nuclear magnetic yield (based on methyl terephthalate as an internal standard) of the objective compound was obtained.
Example 31
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that triethylamine in example 1 was changed to diisopropylethylamine and 1, 2-dichloroethane was changed to dichloromethane, whereby 26% of the target compound (internal standard methyl terephthalate) was obtained as a hydrogen nuclear magnetic yield.
Example 32
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated except for using N, N-dimethylbenzylamine as triethylamine and dichloromethane as 1, 2-dichloroethane in example 1 to obtain a hydrogen nuclear magnetic yield of the objective compound of 19% (using methyl terephthalate as an internal standard).
Example 33
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that the amount of triethylamine in example 1 was changed to 20 mol% and 1, 2-dichloroethane was changed to dichloromethane, whereby a hydrogen nuclear magnetic yield of the objective compound (based on methyl terephthalate as an internal standard) was obtained at 10%.
Example 34
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except for replacing anhydrous 1, 2-dichloroethane with N, N-dimethylformamide to obtain a hydrogen nuclear magnetic yield of the objective compound of 32% (using methyl terephthalate as an internal standard).
Example 35
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that anhydrous 1, 2-dichloroethane in example 1 was changed to dimethyl sulfoxide to obtain a hydrogen nuclear magnetic yield of the objective compound of 48% (using methyl terephthalate as an internal standard).
Example 36
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The same procedures as in example 1 were repeated except for changing the anhydrous 1, 2-dichloroethane to tetrahydrofuran in example 1 to obtain a hydrogen nuclear magnetic yield of the objective compound of 76% (using methyl terephthalate as an internal standard).
Example 37
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The same procedures as in example 1 were repeated except for changing the anhydrous 1, 2-dichloroethane to toluene in example 1 to obtain a hydrogen nuclear magnetic yield of the objective compound of 50% (using methyl terephthalate as an internal standard).
Example 38
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that anhydrous 1, 2-dichloroethane in example 1 was changed to chloroform, whereby 78% of the nuclear magnetic yield of the objective compound (based on methyl terephthalate as an internal standard) was obtained.
Example 39
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The procedure of example 1 was repeated in the same manner as in example 1 except that anhydrous 1, 2-dichloroethane in example 1 was changed to dichloromethane, whereby a hydrogen nuclear magnetic yield of the objective compound of 81% (using methyl terephthalate as an internal standard) was obtained.
Example 40
(E) Preparation of (E) -1-phenyl-4, 4, 4-trifluorobut-2-en-1-one (Compound 1)
The reaction was carried out in the same manner as in example 1 except that the reaction temperature in example 1 was changed to 15 ℃ to obtain a hydrogen nuclear magnetic yield of the objective compound of 80% (using methyl terephthalate as an internal standard).
Claims (8)
1. A process for producing (E) -1-aryl-4, 4, 4-trifluorobut-2-en-1-one compound, which comprises: taking a compound shown in a general formula II as a raw material, and reacting according to the following reaction formula in the presence of an oxidant and alkali to obtain a compound shown in a general formula I;
wherein the content of the first and second substances,
ar is selected from
Wherein X is selected from O, S, N (CH)3) (ii) a n is 1,2, 3,4 and 5, and the wavy line is a connecting position;
r is selected from H, C1-C6 alkyl, phenyl, halogen, trifluoromethyl, trifluoromethoxy, C1-C4 alkoxy, C2-C5 ester group or cyano;
the oxidant is one of pyridine-N-oxide, 2-chloro-pyridine-N-oxide, 2-methyl-pyridine-N-oxide, 4-nitro-pyridine-N-oxide, 4-methyl-pyridine-N-oxide, 2, 6-dichloro-pyridine-N-oxide and 2, 6-dimethyl-pyridine-N-oxide;
the alkali is one of triethylamine, pyrrolidine, 1, 8-diazabicycloundec-7-ene, 4-dimethylamino pyridine, tri-N-butylamine, tetramethyl ethylenediamine, diisopropylethylamine and N, N-dimethylbenzylamine.
2. The method of claim 1, wherein: the amount of the oxidant is 1.0-2.0 times of that of the compound shown in the general formula II.
3. The method of claim 1, wherein: the amount of the alkali substance is 0.2-1.0 times of that of the compound substance shown in the general formula II.
4. The method of claim 1, wherein: the reaction can be carried out under the condition of no solvent or in a solvent, and the solvent is one of tetrahydrofuran, 1, 2-dichloroethane, dichloromethane, chloroform, toluene, N-dimethylformamide and dimethyl sulfoxide.
5. The method of claim 1, wherein: when the reaction is carried out in a solvent, the ratio of the amount of the compound substance represented by the general formula II to the volume of the solvent is 1mmol: 5-15 mL.
6. The method of claim 1, wherein: the reaction temperature is 15-25 ℃, and the reaction time is 3-6 h.
7. The method of claim 1, wherein: and R is one of H, methyl, isopropyl, phenyl, halogen, trifluoromethyl and cyano.
8. The method of claim 1, wherein: the halogen is one of fluorine, chlorine, bromine and iodine.
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