JP7635962B2 - Method for producing fluoroalkyl-substituted vinyl fluoroalkanesulfonyl amides - Google Patents

Description

The present invention relates to a method for producing fluoroalkyl-substituted vinyl fluoroalkanesulfonylamides, preferably perfluoroalkyl-substituted vinyl perfluoroalkanesulfonylamides.

Organofluorine compounds are known to have effects due to the characteristic size and electronic properties of fluorine atoms, such as the mimic effect of three-dimensional molecular recognition in living organisms, which is due to the fact that the atomic radii of fluorine and hydrogen are almost the same; the blocking effect, which protects metabolic sites and avoids the associated toxicity because C-F bonds are stronger than C-H bonds; and the lipophilic effect, which promotes absorption and transport in the body by improving lipid solubility. Numerous medical and agricultural chemicals have been developed through chemical modifications that take advantage of these effects. In addition, methods are being developed to introduce the trifluoromethyl group, which is a mimicking substituent of the methyl group and is more chemically stable than the difluoromethyl and monofluoromethyl groups, and is the substituent with the most proven track record in the practical application of organofluorine compounds.

Sulfonamide compounds are also widely used in herbicides and fungicides. Patent Document 1 discloses a herbicide containing vinyl trifluoromethanesulfonylamide as an active ingredient. On the other hand, vinyl perfluoroalkanesulfonylamides substituted with perfluoroalkyl groups such as trifluoromethyl are expected to be used as agricultural chemical intermediates in view of the properties of the trifluoromethyl group described above, but to the present inventor's knowledge, no examples of their synthesis have been reported.

Japanese Unexamined Patent Publication No. 150258/1983

The present invention aims to provide a method for producing fluoroalkyl-substituted vinyl fluoroalkanesulfonylamides, such as perfluoroalkyl-substituted vinyl perfluoroalkanesulfonylamides, for which no synthesis method has been established until now.

As a result of intensive research to achieve the above object, the inventors discovered that fluoroalkyl-substituted vinyl fluoroalkanesulfonyl amides can be produced by reacting an imine (ketimine) or N-fluoroalkylsulfonylenamine with an excess of fluoroalkylsulfonic anhydride, a base, and a radical initiator, and thus completed the present invention.

That is, the present invention relates to the following.
[1] A method for producing a fluoroalkyl-substituted vinyl fluoroalkanesulfonylamide, comprising reacting a radical initiator in the presence of an imine or N-fluoroalkylsulfonylenamine, a fluoroalkylsulfonic anhydride in an amount exceeding 1 molar equivalent relative to the imine or N-fluoroalkylsulfonylenamine, and a base in an amount exceeding 1 molar equivalent relative to the imine or N-fluoroalkylsulfonylenamine.

（式中、Ｒ^１は、置換基を有していてもよい鎖状炭化水素基、置換基を有していてもよい環状脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、置換基を有していてもよい複素環基、－ＯＲ^３、－ＮＲ^４Ｒ^５、又は、置換基を有していてもよい鎖状炭化水素基と、置換基を有していてもよい環状脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基及び置換基を有していてもよい複素環基からなる群から選択される少なくとも一つの基とが複合した基を表し、 [2] The imine is represented by the following formula (1):

(In the formula, R ¹ represents a chain hydrocarbon group which may have a substituent, a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, -OR ³ , -NR ⁴ R ⁵ , or a group in which a chain hydrocarbon group which may have a substituent and at least one group selected from the group consisting of a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, and a heterocyclic group which may have a substituent are combined,

^R2 represents a hydrogen atom, a chain hydrocarbon group which may have a substituent, a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, or a group in which a chain hydrocarbon group which may have a substituent and at least one group selected from the group consisting of a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, and a heterocyclic group which may have a substituent are combined;

^R3 represents a hydrogen atom, a chain hydrocarbon group which may have a substituent, a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, or a group in which a chain hydrocarbon group which may have a substituent and at least one group selected from the group consisting of a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, and a heterocyclic group which may have a substituent are combined;
R ⁴ and R ⁵ may be the same or different and represent a hydrogen atom, a chain hydrocarbon group which may have a substituent, a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, or a group in which a chain hydrocarbon group which may have a substituent and at least one group selected from the group consisting of a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, and a heterocyclic group which may have a substituent are combined.
The N-fluoroalkylsulfonylenamine is represented by the following formula (2):

（式中、Ｒ^１及びＲ^２は、式（１）におけるＲ^１及びＲ^２と同じ定義であり、Ｒ^ｆはＣ１～Ｃ１０フルオロアルキル基を表す。）で表される
上記〔１〕に記載の製造方法。
〔３〕フルオロアルキルスルホン酸無水物が、以下の式（３）
（Ｒ^ｆＳＯ_２）_２Ｏ （３）
（式中、Ｒ^ｆはＣ１～Ｃ１０フルオロアルキル基を示す）で表される上記〔１〕又は〔２〕に記載の製造方法。

(wherein R ¹ and R ² are defined the same as R ¹ and R ² in formula (1), and R ^f represents a C1-C10 fluoroalkyl group.)
[3] The fluoroalkylsulfonic anhydride is represented by the following formula (3):
(R ^f SO ₂ ) ₂ O (3)
(wherein R ^f represents a C1-C10 fluoroalkyl group).

[4] The method according to any one of the above [1] to [3], wherein the base is selected from 2,6-di-tert-butylpyridine and 2,4,6-tri-tert-butylpyrimidine.
[5] The method according to any one of the above [1] to [4], wherein the radical initiator is selected from azobisisobutyronitrile and 2,2'-azobis(isobutyrate)dimethyl.

By using the manufacturing method of the present invention, it has become possible to provide a method for manufacturing fluoroalkyl-substituted vinyl fluoroalkanesulfonylamides, such as perfluoroalkyl-substituted vinyl perfluoroalkanesulfonylamides, for which no synthesis method has been established until now. The above-mentioned fluoroalkyl-substituted vinyl fluoroalkanesulfonylamides can be used as intermediates for pharmaceuticals and agrochemicals, or as liquid crystal materials, and various fluoroalkyl-substituted vinyl fluoroalkanesulfonylamides can be manufactured by the manufacturing method of the present invention.

The method for producing a fluoroalkyl-substituted vinyl fluoroalkanesulfonylamide of the present invention is a method in which a radical initiator is reacted in the presence of an imine or N-fluoroalkylsulfonylenamine, a fluoroalkylsulfonic anhydride in an amount exceeding 1 molar equivalent relative to the imine or N-fluoroalkylsulfonylenamine, and a base in an amount exceeding 1 molar equivalent relative to the imine or N-fluoroalkylsulfonylenamine. Here, the imine is not particularly limited as long as it is a compound having the following structure (in the formula below, R, R', and R" represent alkyl groups).

The N-fluoroalkylsulfonylenamine is not particularly limited as long as it is a compound containing the following structure (in the following formula, R, R', and R" each represent an alkyl group, and ^Rf represents a fluoroalkyl group).

Specific examples of imines in the present invention include compounds represented by the following formula (1):

（式中、Ｒ^１は、置換基を有していてもよい鎖状炭化水素基、置換基を有していてもよい環状脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、置換基を有していてもよい複素環基、－ＯＲ^３、－ＮＲ^４Ｒ^５、又は、置換基を有していてもよい鎖状炭化水素基と、置換基を有していてもよい環状脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基及び置換基を有していてもよい複素環基からなる群から選択される少なくとも一つの基とが複合した基を表し、

(In the formula, R ¹ represents a chain hydrocarbon group which may have a substituent, a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, -OR ³ , -NR ⁴ R ⁵ , or a group in which a chain hydrocarbon group which may have a substituent and at least one group selected from the group consisting of a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, and a heterocyclic group which may have a substituent are combined,

^R2 represents a hydrogen atom, a chain hydrocarbon group which may have a substituent, a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, or a group in which a chain hydrocarbon group which may have a substituent and at least one group selected from the group consisting of a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, and a heterocyclic group which may have a substituent are combined;

^R3 represents a hydrogen atom, a chain hydrocarbon group which may have a substituent, a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, or a group in which a chain hydrocarbon group which may have a substituent and at least one group selected from the group consisting of a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, and a heterocyclic group which may have a substituent are combined;
^R4 and ^R5 may be the same or different and represent a hydrogen atom, a chain hydrocarbon group which may have a substituent, a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, a heterocyclic group which may have a substituent, or a group in which a chain hydrocarbon group which may have a substituent and at least one group selected from the group consisting of a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, and a heterocyclic group which may have a substituent are combined.

In formula (1), specific examples of the "chain hydrocarbon group" in the "chain hydrocarbon group which may have a substituent" include alkyl groups, alkenyl groups, and alkynyl groups, and may also be groups in which two or three carbon-carbon bonds in an alkyl group have been converted to double bonds, such as alkadienyl groups and alkatrienyl groups.

The alkyl group may be linear or branched, and specific examples include C1-10 alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, and n-decyl.

The term "C1-10" indicates that the parent group has 1 to 10 carbon atoms. This number of carbon atoms does not include the number of carbon atoms in the substituents. For example, a butyl group having an ethoxy group as a substituent is classified as a C2 alkoxy C4 alkyl group. The same meaning will be used throughout the rest of this specification.

The alkenyl group may be linear or branched, and specific examples include C2-10 alkenyl groups such as vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 1-hexenyl, 1-heptenyl, 1-octenyl, 1-nonenyl, and 1-decenyl.

The alkynyl group may be linear or branched, and specific examples include C2-10 alkynyl groups such as ethynyl, 1-propynyl, 1-butynyl, 1-pentynyl, 1-hexynyl, 1-heptynyl, 1-octynyl, and 1-nonyl.

Specific examples of groups in which 2 to 3 carbon-carbon bonds in an alkyl group have been converted to double bonds include alkadienyl groups having 4 to 6 carbon atoms, such as 1,3-butadienyl, and alkatrienyi groups, such as 1,3,5-hexatrienyl, which are groups in which 2 to 3 carbon-carbon bonds in an alkyl group having 1 to 10 carbon atoms have been converted to double bonds.

In formula (1), specific examples of the "cyclic aliphatic hydrocarbon group" in the "cyclic aliphatic hydrocarbon group which may have a substituent" include monocyclic aliphatic hydrocarbon groups or condensed cyclic aliphatic hydrocarbon groups having 3 to 10 members. Specific examples of the monocyclic aliphatic hydrocarbon group include saturated or unsaturated cyclic aliphatic hydrocarbon groups such as cycloalkyl groups, cycloalkenyl groups, and cycloalkadienyl groups.

Specific examples of the cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group, and a cyclodecyl group.

Specific examples of the cycloalkenyl group include 1-cyclopentenyl, 2-cyclopentenyl, 1-cyclohexenyl, 1-cyclobutenyl, and 1-cycloheptenyl groups.

Specific examples of the cycloalkadienyl group include a 2,4-cyclopentadienyl group, a 2,4-cyclohexadienyl group, and a 2,5-cyclohexadienyl group.

The above-mentioned condensed cyclic aliphatic hydrocarbon groups also include those formed by condensing the above-mentioned monocyclic aliphatic hydrocarbon groups with aromatic hydrocarbons which may have a substituent, and specifically include 1-indanyl groups, 2-indanyl groups, 1,2,3,4-tetrahydronaphthalene-1-yl groups, 1,2,3,4,5,6,7,8,9,10-decahydronaphthalene-1-yl groups, 1-hydrindanyl groups, exo- or endo-tricyclo[5.2.1.0]decan-4-yl groups, 2-bornen-5-yl groups, 2-nor Examples include a bornen-5-yl group, an exo- or endo-tricyclo[5.2.1.0]dec-3-en-8-yl group, a 1,2,3,4,5,6,7,8-octahydronaphthalen-1-yl group, a tricyclo[6.2.1.0]undec-4-en-8-yl group, a tetracyclo[6.2.1.1.0]dodec-4-en-9-yl group, a bicyclo[2.2.1]hepta-2,5-dien-3-yl group, and a 3a,4,7,7a-tetrahydroinden-3-yl group.

In formula (1), the "aromatic hydrocarbon group" in the "aromatic hydrocarbon group which may have a substituent" may be a monocyclic or condensed polycyclic group, and specific examples include a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 1-azulenyl group, a 3-indenyl group, a 1-indanyl group, and a 5-tetralinyl group.

In formula (1), specific examples of the "heterocyclic group" in the "heterocyclic group which may have a substituent" include a 5-10 membered monocyclic heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom, a 5-10 membered monocyclic aromatic heterocyclic group, or a fused aromatic heterocycle, and the like. The fused aromatic heterocyclic group includes a benzene ring fused with a monocyclic heterocycle containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom.

Specific examples of the heterocyclic group include a 1-piperidinyl group, a 1-morpholinyl group, a 2-pyrrolyl group, a 2-imidazolyl group, a 2-benzimidazolyl group, a 3-pyrazolyl group, a 2-thiazolyl group, a 3-isothiazolyl group, a 2-oxazolyl group, a 3-isoxazolyl group, a 4-furazanyl group, a 2-pyridinyl group, a 2-pyrazinyl group, a 2-pyrimidinyl group, a 3-pyridazinyl group, a 2-furanyl group, a 2-pyra a 2-phenyl group, a 2-thienyl group, a 2-benzothiophenyl group, a 2-thiopyranyl group, a 1-isothiochromenyl group, a 2-thiochromenyl group, a 9-thioxanthenyl group, a 1-thianthrenyl group, a 1-phenoxathiinyl group, a 1-pyrrolidinyl group, a 5H-1-pyrindin-5-yl group, an indolizin-1-yl group, a 1-isoindolyl group, a 1-indolyl group, a 1-indazolinyl group, a 2-purinyl group, a 1-kylinyl group, a 2-phenylind ... aliphatic acid group, 1-isoquinolinyl group, 2-quinolinyl group, 2,6-naphthyridin-1-yl group, 2,7-naphthyridin-1-yl group, 1-phthalazinyl group, 2-quinoxalinyl group, 2-quinazolinyl group, 3-cinnolinyl group, 2-pteridinyl group, 9-carbazolyl group, 9-β-carbolinyl group, 10-phenanthridinyl group, 9-acridinyl group, 2-perimidinyl group, 1,10-phenanthridinyl group, Examples include 2-aminopropyl group, 1-phenazinyl group, 1-phenothiazinyl group, 1-phenoxazinyl group, 2-antiridinyl group, 1-isobenzofuranyl group, 2-benzofuranyl group, 1-isochromenyl group, 2-chromenyl group, 9-xanthenyl group, parathiazinyl group, 1,2,4-triazol-3-yl group, 1,2,3-triazol-1-yl group, and 5-tetrazolyl group.

In formula (1), "a group in which a chain-like hydrocarbon group which may have a substituent and at least one group selected from the group consisting of a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, and a heterocyclic group which may have a substituent" refers to a group in which the chain-like hydrocarbon group which may have a substituent and at least one group selected from the group consisting of a cyclic aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, and a heterocyclic group which may have a substituent are combined. Specifically, preferred examples of the group in which the chain-like hydrocarbon group which may have a substituent and the cyclic aliphatic hydrocarbon group which may have a substituent are combined, the chain-like hydrocarbon group which may have a substituent and the aromatic hydrocarbon group which may have a substituent are combined, and the chain-like hydrocarbon group which may have a substituent and the heterocyclic group which may have a substituent are combined.

Specific examples of the above "group formed by combining an optionally substituted chain hydrocarbon group and an optionally substituted cyclic aliphatic hydrocarbon group" include cycloalkylalkyl groups such as cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, cycloheptylmethyl group, cyclooctylmethyl group, cyclononylmethyl group, and cyclodecylmethyl group.

Specific examples of the above "group formed by combining an optionally substituted chain hydrocarbon group and an optionally substituted aromatic hydrocarbon group" include a benzyl group, a phenethyl group, and a naphthylmethyl group.

Specific examples of the above "group formed by combining an optionally substituted chain hydrocarbon group and an optionally substituted heterocyclic group" include a 2-piperidinylmethyl group, a 1-morpholinylmethyl group, a 2-pyrrolylmethyl group, a 2-imidazolylmethyl group, a 2-imidazolidinylmethyl group, a 2-benzimidazolylmethyl group, a 3-pyrazolylmethyl group, and a 2-thiazolylmethyl group.

In formula (1), the "substituents" in the "chain hydrocarbon group which may have a substituent", the "cyclic aliphatic hydrocarbon group which may have a substituent", the "aromatic hydrocarbon group which may have a substituent", and the "heterocyclic group which may have a substituent" are not particularly limited as long as they are chemically permissible and have the effect of the present invention.

in particular,
C1 to C10 alkyl groups such as a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an s-butyl group, an i-butyl group, a t-butyl group, an n-pentyl group, an n-hexyl group, an n-heptyl group, an n-octyl group, an n-nonyl group, or an n-decyl group;
C2-6 alkenyl groups such as a vinyl group, a 1-propenyl group, a 2-propenyl group (allyl group), a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 1-methyl-2-propenyl group, or a 2-methyl-2-propenyl group;
C2-6 alkynyl groups such as an ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, or a 1-methyl-2-propynyl group;

C3-8 cycloalkyl groups such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, or a cubanyl group;
C6-10 aryl groups such as a phenyl group or a 1-naphthyl group;
C6-10 aryl C1-6 alkyl groups such as a benzyl group or a phenethyl group;
3- to 6-membered heterocyclyl groups;
3-6 membered heterocyclyl C1-6 alkyl group;

Hydroxyl group;
C1 to C6 alkoxy groups such as a methoxy group, an ethoxy group, an n-propoxy group, an i-propoxy group, an n-butoxy group, an s-butoxy group, an i-butoxy group, or a t-butoxy group;
C2-6 alkenyloxy groups such as a vinyloxy group, an allyloxy group, a propenyloxy group, or a butenyloxy group;
C2-6 alkynyloxy groups such as an ethynyloxy group or a propargyloxy group;
C6-10 aryloxy groups such as a phenoxy group or a 1-naphthoxy group;
C6-10 aryl C1-6 alkoxy groups such as a benzyloxy group or a phenethyloxy group;
5- to 6-membered heteroaryloxy groups such as a 2-thiazolyloxy group or a 2-pyridyloxy group;
5- to 6-membered heteroaryl C1-6 alkyloxy groups such as a 2-thiazolylmethyloxy group or a 2-pyridylmethyloxy group;

Formyl group;
C1-6 alkylcarbonyl groups such as an acetyl group or a propionyl group;
Formyloxy group;
C1-6 alkylcarbonyloxy groups such as an acetyloxy group or a propionyloxy group;
C6-10 arylcarbonyl groups such as a benzoyl group;
C6-10 arylcarbonyloxy groups such as a benzoyloxy group;
C1-6 alkoxycarbonyl groups such as a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an i-propoxycarbonyl group, an n-butoxycarbonyl group, or a t-butoxycarbonyl group;
C1-6 alkoxycarbonyloxy groups such as a methoxycarbonyloxy group, an ethoxycarbonyloxy group, an n-propoxycarbonyloxy group, an i-propoxycarbonyloxy group, an n-butoxycarbonyloxy group, or a t-butoxycarbonyloxy group;
Carboxyl group;

a halogeno group such as a fluoro group, a chloro group, a bromo group, or an iodo group;
C1-6 haloalkyl groups such as a chloromethyl group, a chloroethyl group, a trifluoromethyl group, a 1,2-dichloro-n-propyl group, a 1-fluoro-n-butyl group, or a perfluoro-n-pentyl group;
C2-6 haloalkenyl groups such as a 2-chloro-1-propenyl group or a 2-fluoro-1-butenyl group;
C2-6 haloalkynyl groups such as a 4,4-dichloro-1-butynyl group, a 4-fluoro-1-pentynyl group, or a 5-bromo-2-pentynyl group;
C1-6 haloalkoxy groups such as a trifluoromethoxy group, a 2-chloro-n-propoxy group, or a 2,3-dichlorobutoxy group;
C2-6 haloalkenyloxy groups such as a 2-chloropropenyloxy group or a 3-bromobutenyloxy group;
C1-6 haloalkylcarbonyl groups such as a chloroacetyl group, a trifluoroacetyl group, or a trichloroacetyl group;

Amino group;
C1-6 alkyl-substituted amino groups such as methylamino, dimethylamino, or diethylamino;
C6-10 arylamino groups such as anilino group or 1-naphthylamino group;
C6-10 aryl C1-6 alkylamino groups such as a benzylamino group or a phenethylamino group;
Formylamino group;
C1-6 alkylcarbonylamino groups such as an acetylamino group, a propanoylamino group, a butyrylamino group, or an i-propylcarbonylamino group;
C6-10 arylcarbonylamino groups such as a benzoylamino group;
C1-6 alkoxycarbonylamino groups such as a methoxycarbonylamino group, an ethoxycarbonylamino group, an n-propoxycarbonylamino group, or an i-propoxycarbonylamino group;

unsubstituted or substituted aminocarbonyl groups, such as an aminocarbonyl group, a dimethylaminocarbonyl group, a phenylaminocarbonyl group, or an N-phenyl-N-methylaminocarbonyl group;
imino C1-6 alkyl group such as an iminomethyl group, a 1-iminoethyl group, or a 1-imino-n-propyl group;
Unsubstituted or substituted N-hydroxyimino C1-6 alkyl groups such as an N-hydroxy-iminomethyl group, a 1-(N-hydroxyimino)ethyl group, a 1-(N-hydroxyimino)-n-propyl group, an N-methoxyiminomethyl group, or a 1-(N-methoxyimino)ethyl group;

Aminocarbonyloxy group;
C1-6 alkyl-substituted aminocarbonyloxy groups such as an ethylaminocarbonyloxy group or a dimethylaminocarbonyloxy group;

Mercapto group;
C1 to C6 alkylthio groups, such as a methylthio group, an ethylthio group, an n-propylthio group, an i-propylthio group, an n-butylthio group, an i-butylthio group, an s-butylthio group, or a t-butylthio group;
C1-6 haloalkylthio groups such as a trifluoromethylthio group or a 2,2,2-trifluoroethylthio group;
C6-10 arylthio groups such as a phenylthio group or a 1-naphthylthio group;
5- to 6-membered heteroarylthio groups such as a 2-thiazolylthio group or a 2-pyridylthio group;
C1-6 alkylsulfinyl groups such as a methylsulfinyl group, an ethylsulfinyl group, or a t-butylsulfinyl group;
C1-6 haloalkylsulfinyl groups such as a trifluoromethylsulfinyl group or a 2,2,2-trifluoroethylsulfinyl group;
C6-10 arylsulfinyl groups such as a phenylsulfinyl group or a 1-naphthylsulfinyl group;
5- to 6-membered heteroarylsulfinyl groups such as a 2-thiazolylsulfinyl group or a 2-pyridylsulfinyl group;
C1 to C6 alkylsulfonyl groups such as a methylsulfonyl group, an ethylsulfonyl group, or a t-butylsulfonyl group;
C1-6 haloalkylsulfonyl groups such as a trifluoromethylsulfonyl group or a 2,2,2-trifluoroethylsulfonyl group;
C6-10 arylsulfonyl groups such as a phenylsulfonyl group or a 1-naphthylsulfonyl group;
5- to 6-membered heteroarylsulfonyl groups such as a 2-thiazolylsulfonyl group or a 2-pyridylsulfonyl group;
C1 to C6 alkylsulfonyloxy groups such as a methylsulfonyloxy group, an ethylsulfonyloxy group, or a t-butylsulfonyloxy group;
C1-6 haloalkylsulfonyloxy groups such as a trifluoromethylsulfonyloxy group or a 2,2,2-trifluoroethylsulfonyloxy group;

Tri-C1-6 alkyl-substituted silyl groups such as a trimethylsilyl group, a triethylsilyl group, or a t-butyldimethylsilyl group;
triC1-6 alkyl-substituted silyloxy groups such as a trimethylsilyloxy group, a triethylsilyloxy group, or a t-butyldimethylsilyloxy group;
Tri-C6-10 aryl-substituted silyl groups such as triphenylsilyl groups;
Tri-C6-10 aryl-substituted silyloxy groups such as triphenylsilyloxy groups;
Examples include a cyano group or a nitro group.

In addition, any of the hydrogen atoms in these "substituents" may be replaced with a group of a different structure. Specific examples of the "substituents" in this case include a C1-6 alkyl group, a C1-6 haloalkyl group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, a halogeno group, a cyano group, and a nitro group.

The above "3- to 6-membered heterocyclyl group" includes 1 to 4 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur atoms as ring constituent atoms. The heterocyclyl group may be either monocyclic or polycyclic. In the case of a polycyclic heterocyclyl group, as long as at least one ring is a heterocycle, the remaining rings may be either a saturated alicyclic ring, an unsaturated alicyclic ring, or an aromatic ring. Specific examples of the "3- to 6-membered heterocyclyl group" include a 3- to 6-membered saturated heterocyclyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered partially unsaturated heterocyclyl group.

Specific examples of 3- to 6-membered saturated heterocyclyl groups include 2-aziridinyl groups, 2-epoxy groups, 2-pyrrolidinyl groups, 2-tetrahydrofuranyl groups, 2-thiazolidinyl groups, 2-piperidyl groups, 2-piperazinyl groups, 1-morpholinyl groups, 2-dioxolanyl groups, and 2-dioxanyl groups.

Specific examples of 5-membered heteroaryl groups include 2-pyrrolyl, 2-furyl, 2-thienyl, 2-imidazolyl, 3-pyrazolyl, 2-oxazolyl, 3-isoxazolyl, 2-thiazolyl, 3-isothiazolyl, 1,2,4-triazol-3-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-thiadiazol-3-yl, and 5-tetrazolyl groups.

Specific examples of six-membered heteroaryl groups include 2-pyridyl groups, 3-pyrazinyl groups, 2-pyrimidinyl groups, 2-pyridazinyl groups, and 1,3,5-triazin-2-yl groups.

The 5- to 6-membered partially unsaturated heterocyclyl group is, for example, a 2-oxazolinyl group or a 3-isoxazolinyl group.

Specific examples of 3- to 6-membered heterocyclyl C1-6 alkyl groups include 2-aziridinylmethyl, glycidyl, 2-pyrrolidylmethyl, 2-tetrahydrofuranylmethyl, 2-thiazolidinylmethyl, 2-pyrrolylmethyl, 2-furylmethyl, 2-imidazolylmethyl, 2-pyridylmethyl, and 4-pyridylmethyl groups.

In R ¹ of formula (1), specific examples of R ³ in "-OR ³ " include the same functional groups as those exemplified as the functional groups of R ¹ . Specific examples of "-OR ³ " include C1-6 alkoxy groups such as methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, i-butoxy, or t-butoxy; C2-6 alkenyloxy groups such as vinyloxy, allyloxy, propenyloxy, or butenyloxy; C2-6 alkynyloxy groups such as ethynyloxy or propargyloxy; C6-10 aryloxy groups such as phenoxy or 1-naphthoxy; C6-10 aryl C1-6 alkoxy groups such as benzyloxy or phenethyloxy; 5- to 6-membered heteroaryloxy groups such as 2-thiazolyloxy or 2-pyridyloxy; and 5- to 6-membered heteroaryl C1-6 alkyloxy groups such as thiazolylmethyloxy or pyridylmethyloxy.

In R ¹ of formula (1), specific examples of R ⁴ and R ⁵ of "-NR ⁴ R ⁵ " include the same functional groups as those exemplified as the functional group of R ^1. Specific examples of "-NR ⁴ R ⁵ " include C1-6 alkyl-substituted amino groups such as a methylamino group, a dimethylamino group, or a diethylamino group, C6-10 arylamino groups such as an anilino group or a 1-naphthylamino group, or C6-10 aryl C1-6 alkylamino groups such as a benzylamino group or a phenethylamino group.

Specific examples of N-fluoroalkylsulfonylenamines in the present invention include compounds represented by the following formula (2):

In formula (2), R ¹ and R ² are defined the same as R ¹ and R ² in formula (1), and R ^f represents a C1 to C10 fluoroalkyl group.

In formula (2), the "C1-C10 fluoroalkyl group" of ^Rf may be an alkyl group in which all of the hydrogen atoms are replaced by fluorine atoms ₍ perfluoroalkyl group), or an alkyl group in which some of _the hydrogen atoms are replaced by fluorine atoms, and _{specifically includes} perfluoroalkyl groups such _{as CF3 , C2F5} , _C3F7 , _{C4F9 , C5F11 , C6F13 , C7F15 , or C8F17 , CF2H , CFH2 , CF2CF2H , CH2CF3 , CH2CH2CF3 , CH2C2F5 , CH2CH2C2F5 , CH2C3F7 , CH2CH2C3F7 , CH2} Examples include partially fluorinated alkyl groups such as _C4F9 or _CH2CH2C4F9 . Among these, fluoroalkyl groups in which 60% or more of _the hydrogen atoms in _the alkyl group are substituted with fluorine atoms are preferred, _with 70% or more, 80% or more _, and 90% or more being more preferred. Furthermore, among these, C1-C6 fluoroalkyl groups are preferred, and C1-C3 fluoroalkyl groups are more preferred, _{with CF3, CF2CF2H} , and _{CF2CF3 being} particularly preferred.

Specific examples of the fluoroalkylsulfonic anhydride in the present invention include compounds represented by the following formula (3).
(R ^f SO ₂ ) ₂ O (3)
(In the formula, ^Rf has the same definition as ^Rf in formula (2).)

In the present invention, when an N-fluoroalkylsulfonylenamine is used as a starting material, the fluoroalkyl groups of the N-fluoroalkylsulfonylenamine and the fluoroalkylsulfonic anhydride may be made different from each other to produce a fluoroalkyl-substituted vinylfluoroalkanesulfonylamide having two different fluoroalkyl groups. Here, the N-fluoroalkylsulfonylenamine may be synthesized by reacting an imine with a fluoroalkylsulfonic anhydride in the presence of more than 1 molar equivalent of a base relative to the imine.

In the production method of the present invention, the reaction can be carried out without a solvent or in an organic solvent. Specific examples of the organic solvent used include organic halogen-based solvents such as chloroform, dichloromethane, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane, chlorobenzene, o-dichlorobenzene, 1,3,5-trichlorobenzene, bromobenzene, iodobenzene, trifluoromethylbenzene, fluorobenzene, and difluorobenzene; aromatic hydrocarbons such as benzene, toluene, xylene, and mesitylene; dimethylformamide (DMF), dimethyl sulfoxide (DMSO), diethyl ether, diisopropyl ether, and di(n-butyl) ether. Examples of suitable solvents include aprotic polar solvents such as ether, monoglyme, diglyme, triglyme, tetrahydrofuran, 1,4-dioxane, anisole, veratrole, diethyl sulfide, di(n-butyl) sulfide, acetonitrile, propionitrile, or benzonitrile; and aliphatic hydrocarbons such as pentane, hexane, cyclopentane, or cyclohexane. Among these, organic halogen-based solvents are preferred, and further, dichloromethane or 1,2-dichloroethane, and more preferably dehydrated dichloromethane or dehydrated 1,2-dichloroethane, can be used.

The amount of these organic solvents used is not particularly limited, but is preferably in the range of 0.5 to 20 times by weight relative to the imine or N-fluoroalkylsulfonylenamine.

In the production method of the present invention, the amount of fluoroalkylsulfonic anhydride used relative to the imine or N-fluoroalkylsulfonylenamine may be more than 1 molar equivalent, for example, 1.1 molar equivalents or more, 1.5 molar equivalents or more, 2 molar equivalents or more, 3 molar equivalents or more, and although there is no particular upper limit, for example, 5 molar equivalents or less.

Specific examples of the base in the present invention include organic bases such as triethylamine, diisopropylethylamine, pyridine, 2,6-lutidine, 2,6-dichloropyridine, 2,4,6-trimethylpyridine, 2,4,6-tri-tert-butylpyridine, 2,6-di-tert-butyl-4-methylpyridine, 2,6-di-tert-butylpyridine, and 2,4,6-tri-tert-butylpyrimidine, and inorganic bases such as potassium carbonate and sodium carbonate. Among these, the bulky bases 2,4,6-tri-tert-butylpyridine, 2,6-di-tert-butyl-4-methylpyridine, 2,6-di-tert-butylpyridine, and 2,4,6-tri-tert-butylpyrimidine are preferred.

The amount of base used relative to the imine or N-fluoroalkylsulfonylenamine in the production method of the present invention may be more than 1 molar equivalent, for example 2 molar equivalents or more, 3 molar equivalents or more, 4 molar equivalents or more, 5 molar equivalents or more, and although there is no particular upper limit, for example 10 molar equivalents or less.

The radical initiator in the manufacturing method of the present invention is not particularly limited as long as it generates radicals from the starting material, but specific examples include a trialkylborane compound such as triethylborane or tributylborane and molecular oxygen, a dialkylzinc such as diethylzinc and molecular oxygen, an azo compound such as azobisisobutyronitrile or 2,2'-azobis(isobutyrate)dimethyl, or a peroxide compound such as di(t-butyl)peroxide. Of these, a combination of a trialkylborane compound and molecular oxygen, azobisisobutyronitrile, or 2,2'-azobis(isobutyrate)dimethyl is preferred, and triethylborane is preferred as the trialkylborane compound.

In the production method of the present invention, the amount of radical initiator used relative to the imine or N-fluoroalkylsulfonylenamine is preferably in the range of 0.1 to 1.0 equivalents in molar ratio. A trace amount of molecular oxygen is sufficient. In addition, methods for generating radicals from the starting material can also be used in which an azo compound is added and irradiated with light, or in which a peroxide is added and irradiated with light.

The reaction temperature in the production method of the present invention is not particularly limited, but is usually -100°C to 150°C, preferably 0°C to 100°C, more preferably 10°C to 50°C, and even more preferably 15°C to 30°C. The reaction can also be carried out at room temperature. The reaction pressure can be carried out under normal pressure or pressure, but normal pressure is preferred. The reaction time is usually 1 minute to 200 hours, preferably 1 hour to 10 hours, more preferably 1 hour to 5 hours, and even more preferably 1 hour to 3 hours. It is desirable to carry out the reaction under sufficient stirring. After the reaction, an acid such as acetic acid or hydrochloric acid or water is added to inactivate the reaction agent and insoluble matter is removed, and then the fluoroalkyl-substituted vinyl fluoroalkanesulfonylamide can be isolated by purification such as known distillation, extraction, crystallization, recrystallization, and chromatography.

The fluoroalkyl-substituted vinyl fluoroalkanesulfonylamide obtained by the manufacturing method of the present invention is a reaction product of the above-mentioned imine and a fluoroalkylsulfonic acid anhydride, and specifically includes a compound represented by the following formula (4):

In formula (4), R ¹ , R ² and R ^f are defined the same as R ¹ and R ² in formula (1) and R ^f in formula (2). When an N-fluoroalkylsulfonylenamine is used as a starting material, the two R ^fs may be the same or different.

The compound represented by the above formula (4) may have one or more asymmetric carbon atoms and may have geometric isomerism or axial chirality, and may exist as multiple stereoisomers. These stereoisomers, their mixtures, and racemates are included in the compound represented by formula (4). The fluoroalkyl-substituted vinyl fluoroalkanesulfonylamide obtained by the production method of the present invention can be suitably used as a synthetic intermediate for pharmaceuticals and agricultural chemicals.

The production method of the present invention is a very simple and distinctive method in that it can carry out a three-step reaction in one pot using an imine and a fluoroalkylsulfonic anhydride as starting materials, and a radical initiator acts on the N-fluoroalkylsulfonylenamine intermediate formed by the addition of fluoroalkylsulfonic acid to the N of the imine, and then a fluoroalkyl group is added. Alternatively, it is a very simple and distinctive method in that it can carry out a two-step reaction in one pot using an N-fluoroalkylsulfonylenamine as a starting material, and then a radical initiator acts on the N-fluoroalkyl group is added. Therefore, it is expected to be widely used in the synthesis of pharmaceuticals and agricultural chemicals.

The present invention will be described in more detail below using examples, but the technical scope of the present invention is not limited to these examples.
[Example 1] to [Example 9]

Using the manufacturing method of the present invention, fluoroalkyl-substituted vinyl fluoroalkanesulfonylamide (compound 2 in Table 1) was manufactured as shown in Table 1 below. The detailed procedure is as described below.

Example 1: Synthesis of 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-methoxyphenyl)-1-propen-1-yl)methanesulfonamide

A stirrer was added to a 10 mL two-necked eggplant flask and the flask was flame-dried. 62.7 mg (0.28 mmol) of (E)-1-(4-methoxyphenyl)-N-phenylethane-1-imine, 217.9 mg (0.88 mmol, 3.1 equiv) of 2,4,6-tri-tert-butylpyrimidine (TTBP), and 11.2 mg (0.05 mmol) of 2,2'-azobis(isobutyrate)dimethyl (V-601) were added thereto and substituted with nitrogen. Next, 2 mL of 1,2-dichloroethane and 0.13 mL (0.77 mmol, 2.8 equiv) of Tf ₂ O were added and stirred for 3 hours while heating at 80°C. After stirring to room temperature, 10 mL of 1M hydrochloric acid was added and stirred for 30 minutes. The mixture was then extracted with dichloromethane and dehydrated with sodium sulfate. The mixture was transferred to a one-necked eggplant flask and concentrated. 15.9 mg (0.09 mmol) of 1,1,2,2-tetrachloroethane was added as an internal standard and NMR measurement was performed. The yield was calculated from the obtained integral ratio, and the target product 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-methoxyphenyl)-1-propen-1-yl)methanesulfonamide (72%) and intermediate 1,1,1-trifluoro-N-(1-(4-methoxyphenyl)vinyl)-N-phenylmethanesulfonamide (19%) were obtained, respectively. Isolation and purification were performed by silica gel column chromatography, and 70.0 mg (0.16 mmol, 59%) of the target product and 26.6 mg (0.07 mmol, 27%) of the intermediate were obtained.
1H-NMR (500MHz, CDCl3) δ7.29 (q, J = 2.5Hz, 3H), 7.18-7.21 (m, 4H ), 6.80 (dt, J=9.2, 2.4Hz, 2H), 6.25 (q, J=7.1Hz, 1H), 3.78 (s, 3H)

Example 2 Synthesis of 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-fluorophenyl)-1-propen-1-yl)methanesulfonamide

A stirrer was added to a 10 mL two-necked eggplant flask and the flask was flame-dried. 53.7 mg (0.25 mmol) of (E)-1-(4-fluorophenyl)-N-phenylethane-1-imine, 215.3 mg (0.87 mmol, 3.5 equiv) of 2,4,6-tri-tert-butylpyrimidine (TTBP), and 12.1 mg (0.05 mmol) of 2,2'-azobis(isobutyrate)dimethyl (V-601) were added thereto and substituted with nitrogen. Next, 2 mL of 1,2-dichloroethane and 0.13 mL (0.77 mmol, 3.1 equiv) of Tf ₂ O were added and stirred for 3 hours while heating at 80°C. After stirring to room temperature, 10 mL of 1M hydrochloric acid was added and stirred for 30 minutes. The mixture was then extracted with dichloromethane and dehydrated with sodium sulfate. The mixture was transferred to a one-necked eggplant flask and concentrated. 14.4 mg (0.09 mmol) of 1,1,2,2-tetrachloroethane was added as an internal standard and NMR measurement was performed. The yield was calculated from the obtained integral ratio, and the target product 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-fluorophenyl)-1-propen-1-yl)methanesulfonamide (60%) and intermediate 1,1,1-trifluoro-N-(1-(4-fluorophenyl)vinyl)-N-phenylmethanesulfonamide (26%) were obtained, respectively. Isolation and purification were performed by silica gel column chromatography, and 48.0 mg (0.12 mmol, 46%) of the target product and 20.8 mg (0.06 mmol, 21%) of the intermediate were obtained.
1H-NMR (500MHz, CDCl3) δ7.33-7.28 (m, 3H), 7.22-7.16 (m, 4H), 6.98 (tt, J=9.0, 2.4Hz, 2H), 6.32 (q, J=7.3Hz, 1H); 13C-NMR (126MHz, CDC l3) δ163.54 (d, JC-F=252Hz), 147.28 (q, JC-F=4.8Hz), 135.70, 131. 21 (d, JC-F=8.4Hz), 129.81, 129.58, 129.48, 128.16 (d, JC-F=3.6Hz ), 121.74 (q, JC-F = 271 Hz), 119.97 (q, JC-F = 324 Hz), 117.97 (q, JC-F = 36 Hz), 115.54 (d, JC-F = 22 Hz); 19F-NMR (471 MHz, CDCl3) δ - 56.21 (d , J=6.8Hz, 3F), -72.51 (s, 3F), -109.13 (tt, J=8.2, 5.5Hz, 1F); HRMS (ESI-TOF) calcdforC16H9NO2F7S ([M-1]-)412.0242, found412.0242

Example 3 Synthesis of 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-chlorophenyl)-1-propen-1-yl)methanesulfonamide

A stirrer was added to a 10 mL two-necked eggplant flask and the flask was flame-dried. 58.8 mg (0.26 mmol) of (E)-1-(4-chlorophenyl)-N-phenylethane-1-imine, 216.4 mg (0.87 mmol, 3.4 equiv) of 2,4,6-tri-tert-butylpyrimidine (TTBP), and 13.0 mg (0.06 mmol) of 2,2'-azobis(isobutyrate)dimethyl (V-601) were added thereto and substituted with nitrogen. Next, 2 mL of 1,2-dichloroethane and 0.13 mL (0.77 mmol, 3.0 equiv) of Tf ₂ O were added and stirred for 3 hours while heating at 80°C. After stirring to room temperature, 10 mL of 1M hydrochloric acid was added and stirred for 30 minutes. The mixture was then extracted with dichloromethane and dehydrated with sodium sulfate. The mixture was transferred to a one-necked eggplant flask and concentrated. 13.3 mg (0.09 mmol) of 1,1,2,2-tetrachloroethane was added as an internal standard and NMR measurement was performed. The yield was calculated from the obtained integral ratio, and the target product 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-chlorophenyl)-1-propen-1-yl)methanesulfonamide (77%) and intermediate 1,1,1-trifluoro-N-(1-(4-chlorophenyl)vinyl)-N-phenylmethanesulfonamide (20%) were obtained. Isolation and purification were performed by silica gel column chromatography, and 55.0 mg (0.13 mmol, 50%) of the target product and 13.9 mg (0.04 mmol, 15%) of the intermediate were obtained.
1H-NMR (500MHz, CDCl3) δ7.34-7.25 (m, 5H), 7.19-7.14 (m, 4H), 6.33 (q, J = 7.3Hz, 1H); 13C-NMR (126MHz, C DCl3) δ147.12 (q, JC-F=6Hz), 136.51, 135.60, 130.58, 130.41, 129.88, 129.64, 129.45, 128.62, 121.69 ( 19F-NMR (471 MHz, CDCl3) δ-56.21 (d, J= 6.8Hz, 3F), -72.51 (s, 3F); HRMS (ESI-TOF) calcdforC16H9NO2F6S35Cl ([M-1]-)427.9947, found427.9947

Example 4 Synthesis of 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-bromophenyl)-1-propen-1-yl)methanesulfonamide

A stirrer was added to a 10 mL two-necked eggplant flask and the flask was flame-dried. 69.3 mg (0.25 mmol) of (E)-1-(4-bromophenyl)-N-phenylethane-1-imine, 216.3 mg (0.87 mmol, 3.5 equiv) of 2,4,6-tri-tert-butylpyrimidine (TTBP), and 14.2 mg (0.06 mmol) of 2,2'-azobis(isobutyrate)dimethyl (V-601) were added thereto and substituted with nitrogen. Next, 2 mL of 1,2-dichloroethane and 0.13 mL (0.77 mmol, 3.1 equiv) of Tf ₂ O were added and stirred for 3 hours while heating at 80°C. After stirring to room temperature, 10 mL of 1M hydrochloric acid was added and stirred for 30 minutes. The mixture was then extracted with dichloromethane and dehydrated with sodium sulfate. The mixture was transferred to a one-necked eggplant flask and concentrated. 14.8 mg (0.09 mmol) of 1,1,2,2-tetrachloroethane was added as an internal standard and NMR measurement was performed. The yield was calculated from the obtained integral ratio, and the target product 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-bromophenyl)-1-propen-1-yl)methanesulfonamide (70%) and intermediate 1,1,1-trifluoro-N-(1-(4-bromophenyl)vinyl)-N-phenylmethanesulfonamide (17%) were obtained. Isolation and purification were performed by silica gel column chromatography, and 60.7 mg (0.13 mmol, 51%) of the target product and 34.4 mg (0.08 mmol, 34%) of the intermediate were obtained.

13C-NMR (126MHz, CDCl3) δ147.14 (q, JC-F=6Hz), 135.57, 131.58, 131.06, 130.58, 1 29.89, 129.65, 129.44, 124.85, 121.67 (q, JC-F=271Hz), 119.94 (q, JC-F=324Hz), 11 8.22 (q, JC-F = 34 Hz); 19F-NMR (471 MHz, CDCl3) δ -56.20 (d, J = 8.2 Hz, 3F), -72.52 (s, 3F); HRMS (ESI-TOF) calcdforC16H9NO2F6S79Br ([M-1]-)471.9442, found471.9440

Example 5 Synthesis of 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-iodophenyl)-1-propen-1-yl)methanesulfonamide A stirrer was added to a 10 mL two-necked eggplant flask and flame dried. 80.8 mg (0.25 mmol) of (E)-1-(4-iodophenyl)-N-phenylethan-1-imine, 220.3 mg (0.89 mmol, 3.5 equiv) of 2,4,6-tri-tert-butylpyrimidine (TTBP), and 11.7 mg (0.05 mmol) of 2,2'-azobis(isobutyrate) dimethyl (V-601) were added and replaced with nitrogen. Next, 2 mL of 1,2-dichloroethane and 0.13 mL (0.77 mmol, 3.1 equiv) of Tf ₂ O were added and stirred for 3 hours while heating at 80°C. After stirring to room temperature, 10 mL of 1 M hydrochloric acid was added and stirred for 30 minutes. It was then extracted with dichloromethane and dehydrated with sodium sulfate. It was transferred to a one-necked eggplant flask and concentrated. 15.0 mg (0.09 mmol) of 1,1,2,2-tetrachloroethane was added as an internal standard and NMR measurement was performed. The yield was calculated from the integral ratio, and the target product 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-iodophenyl)-1-propen-1-yl)methanesulfonamide (72%) and intermediate 1,1,1-trifluoro-N-(1-(4-iodophenyl)vinyl)-N-phenylmethanesulfonamide (26%) were obtained. Isolation and purification were carried out by silica gel column chromatography, and 68.1 mg (0.13 mmol, 52%) of the target product and 29.2 mg (0.06 mmol, 22%) of the intermediate were obtained.

1H-NMR (500MHz, CDCl3) δ7.63 (dt, J=8.6, 2.0Hz, 2H), 7.33-7.29 (m, 3H), 7.16 (dd, J=8.0, 1.7Hz, 2H), 6.93 (dt, J=8.8, 2. 1Hz, 2H), 6.31 (q, J = 7.3Hz, 1H); 13C-NMR (126MHz, CDCl3) δ147.25 (q, JC-F = 6Hz), 137.50, 135.56, 131.64, 130.57, 129.89 , 129.65, 129.43, 121.66 (q, JC-F = 271 Hz), 119.93 (q, JC-F = 325 Hz), 118.20 (q, JC-F = 36 Hz), 96.93; 19F-NMR (471 MHz, CDC l3) δ-56.17 (d, J=8.2Hz, 3F), -72.47 (s, 3F); HRMS (ESI-TOF) calcdforC16H9NO2F6SI ([M-1]-) 519.9303, found519.9303

Example 6 Synthesis of 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-(methylsulfonyl)phenyl)-1-propen-1-yl)methanesulfonamide

A stirrer was added to a 10 mL two-necked eggplant flask and the flask was flame-dried. 52.3 mg (0.19 mmol) of (E)-1-(4-(methylsulfonyl)phenyl)-N-phenylethane-1-imine, 219.5 mg (0.88 mmol, 4.7 equiv) of 2,4,6-tri-tert-butylpyrimidine (TTBP), and 14.0 mg (0.06 mmol) of 2,2'-azobis(isobutyrate)dimethyl (V-601) were added thereto and substituted with nitrogen. Next, 2 mL of 1,2-dichloroethane and 0.13 mL (0.77 mmol, 4.1 equiv) of Tf ₂ O were added and stirred for 3 hours while heating at 80°C. After stirring to room temperature, 10 mL of 1M hydrochloric acid was added and stirred for 30 minutes. The mixture was then extracted with dichloromethane and dehydrated with sodium sulfate. This was transferred to a one-necked eggplant flask and concentrated. 10.8 mg (0.09 mmol) of 1,1,2,2-tetrachloroethane was added as an internal standard and NMR measurement was performed. The yield was calculated from the obtained integral ratio, and the target product 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-(methylsulfonyl)phenyl)-1-propen-1-yl)methanesulfonamide (61%) and intermediate 1,1,1-trifluoro-N-(1-(4-(methylsulfonyl)phenyl)vinyl)-N-phenylmethanesulfonamide (39%) were obtained, respectively. Isolation and purification were performed by silica gel column chromatography, and 42.0 mg (0.09 mmol, 46%) of the target product and 24.7 mg (0.06 mmol, 18%) of the intermediate were obtained.

1H-NMR (500MHz, CDCl3) δ7.87 (d, J = 8.0Hz, 2H), 7.41 (d, J = 8.6Hz, 2H), 7.30-7.35 (m, 3H), 7.16 (d, J = 6.9Hz) , 2H), 6.41 (q, J = 7.3Hz, 1H), 3.04 (s, 3H); 19F-NMR (471MHz, CDCl3) δ -56.14 (d, J = 8.2Hz, 3F), -72.43 (s, 3F)

Example 7 Synthesis of methyl 4-(3,3,3-trifluoro-1-((1,1,1-trifluoro-N-phenylmethyl)sulfonamido)-1-propen-1-yl)benzoate

A stirrer was added to a 10 mL two-necked eggplant flask and the flask was flame-dried. 63.1 mg (0.25 mmol) of (E)-4-(1-(phenylimino)ethyl)methyl benzoate, 217.1 mg (0.87 mmol, 3.5 equiv) of 2,4,6-tri-tert-butylpyrimidine (TTBP), and 12.8 mg (0.06 mmol) of 2,2'-azobis(isobutyrate)dimethyl (V-601) were added thereto and substituted with nitrogen. Next, 2 mL of 1,2-dichloroethane and 0.13 mL (0.77 mmol, 3.1 equiv) of Tf ₂ O were added and stirred for 3 hours while heating at 80°C. After stirring to room temperature, 10 mL of 1M hydrochloric acid was added and stirred for 30 minutes. The mixture was then extracted with dichloromethane and dehydrated with sodium sulfate. The mixture was transferred to a one-necked eggplant flask and concentrated. 21.3 mg (0.09 mmol) of 1,1,2,2-tetrachloroethane was added as an internal standard and NMR measurement was performed. The yield was calculated from the obtained integral ratio, and the target product 4-(3,3,3-trifluoro-1-((1,1,1-trifluoro-N-phenylmethyl)sulfonamido)-1-propen-1-yl)methyl benzoate (71%) and intermediate 4-(1-((1,1,1-trifluoro-N-phenylmethyl)sulfonamido)vinyl)methyl benzoate (24%) were obtained. Isolation and purification were performed by silica gel column chromatography, and 59.2 mg (0.13 mmol, 52%) of the target product and 17.9 mg (0.05 mmol, 17%) of the intermediate were obtained.

1H-NMR (500MHz, CDCl3) δ7.95 (dt, J = 8.4, 1.9Hz, 2H), 7.32-7.27 (m, 5H), 7.16 (dt, J = 6.3, 1.9Hz, 2H), 6.37 (q, J = 7.3Hz, 1 H), 3.90 (s, 3H); 13C-NMR (126MHz, CDCl3) δ166.08, 147.12 (q, JC-F=6Hz), 136.46, 135.47, 131.61, 129.91, 129.62, 129.5 1,129.37, 129.16, 121.61 (q, JC-F = 271 Hz), 119.93 (q, JC-F = 324 Hz), 118.25 (q, JC-F = 35 Hz), 52.34; 19F-NMR (471 MHz, CD Cl3) δ-56.21 (d, J = 6.8 Hz, 3F), -72.53 (s, 3F); HRMS (ESI-TOF) calcd for C18H12NO4F6S ([M-1]-) 452.0391, found 452.0392

Example 8 Synthesis of 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-cyanophenyl)-1-propen-1-yl)methanesulfonamide

A stirrer was added to a 10 mL two-necked eggplant flask and the flask was flame-dried. 54.4 mg (0.25 mmol) of (E)-1-(4-cyanophenyl)-N-phenylethane-1-imine, 215.4 mg (0.87 mmol, 3.5 equiv) of 2,4,6-tri-tert-butylpyrimidine (TTBP), and 13.6 mg (0.06 mmol) of 2,2'-azobis(isobutyrate)dimethyl (V-601) were added thereto and substituted with nitrogen. Next, 2 mL of 1,2-dichloroethane and 0.13 mL (0.77 mmol, 3.1 equiv) of Tf ₂ O were added and stirred for 3 hours while heating at 80°C. After stirring to room temperature, 10 mL of 1M hydrochloric acid was added and stirred for 30 minutes. The mixture was then extracted with dichloromethane and dehydrated with sodium sulfate. The mixture was transferred to a one-necked eggplant flask and concentrated. 10.1 mg (0.09 mmol) of 1,1,2,2-tetrachloroethane was added as an internal standard and NMR measurement was performed. The yield was calculated from the obtained integral ratio, and the target product 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-cyanophenyl)-1-propen-1-yl)methanesulfonamide (58%) and intermediate 1,1,1-trifluoro-N-(1-(4-cyanophenyl)vinyl)-N-phenylmethanesulfonamide (26%) were obtained, respectively. Isolation and purification were performed by silica gel column chromatography, and 45.6 mg (0.11 mmol, 44%) of the target product and 20.7 mg (0.06 mmol, 25%) of the intermediate were obtained.
1H-NMR (500MHz, CDCl3) δ7.58 (d, J = 8.0Hz, 2H), 7.31-7.36 (m, 5H), 7.15-7.16 (m, 2H), 6.39 ( q, J = 7.3Hz, 1H); 19F-NMR (471MHz, CDCl3) δ -56.20 (d, J = 8.2Hz, 3F), -72.47 (d, J = 2.7Hz, 3F)

Example 9: Synthesis of 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(naphthalene-1-yl)-1-propen-1-yl) methanesulfonamide

A stirrer was added to a 10 mL two-necked eggplant flask and the flask was flame-dried. 63.3 mg (0.26 mmol) of (E)-1-(naphthalene-1-yl)-N-phenylethane-1-imine, 218.4 mg (0.88 mmol, 3.4 equiv) of 2,4,6-tri-tert-butylpyrimidine (TTBP), and 11.0 mg (0.05 mmol) of 2,2'-azobis(isobutyrate)dimethyl (V-601) were added thereto and substituted with nitrogen. Next, 2 mL of 1,2-dichloroethane and 0.13 mL (0.77 mmol, 3.0 equiv) of Tf ₂ O were added and stirred for 3 hours while heating at 80°C. After stirring to room temperature, 10 mL of 1M hydrochloric acid was added and stirred for 30 minutes. The mixture was then extracted with dichloromethane and dehydrated with sodium sulfate. The mixture was transferred to a one-necked eggplant flask and concentrated. 13.4 mg (0.09 mmol) of 1,1,2,2-tetrachloroethane was added as an internal standard and NMR measurement was performed. The yield was calculated from the obtained integral ratio, and the target product 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(naphthalene-1-yl)-1-propen-1-yl)methanesulfonamide (9%) and intermediate 1,1,1-trifluoro-N-(1-(naphthalene-1-yl)vinyl)-N-phenylmethanesulfonamide (79%) were obtained, respectively. Isolation and purification were performed by silica gel column chromatography, and 8.5 mg (0.02 mmol, 7%) of the target product and 61.1 mg (0.16 mmol, 52%) of the intermediate were obtained.

1H-NMR (500MHz, CDCl3) δ7.80 (d, J = 8.0Hz, 1H), 7.77 (d, J = 8.6Hz, 1H), 7.77 (d, J=8.0Hz, 1H), 7.67 (s, 1H), 7.54-7.47 (m, 2H), 7.35 (dd, J=8.6, 1.7Hz, 1H), 7.25-7.19 (m, 5H), 6.39 (q, J = 7.3Hz, 1H); 13C-NMR (126MHz , CDCl3) δ148.28 (q, JC-F=6Hz), 135.78, 133.61, 132.27, 129.79, 129.6 8,129.47,129.38,128.50,128.16,127.71,127.55,126.75,125.24,1 21.88 (q, JC-F=270Hz), 120.04 (q, JC-F=325Hz), 117.93 (q, JC-F=35Hz) ; 19F-NMR (471 MHz, CDCl3) δ -56.05 (d, J = 8.2 Hz, 3F), -72.38 (s, 3F); HRM S(ESI-TOF)calcdforC20H12NO2F6S([M-1]-)444.0493, found444.0493
[Example 10]

Synthesis of 1,1,1-trifluoro-N-(3,3,4,4,5,5,6,6,6-nonafluoro-1-(4-methoxyphenyl)-1-hexen-1-yl)-N-phenylmethanesulfonamide

A stirrer was added to a 10 mL two-necked eggplant flask and flame dried. 118.0 mg (0.233 mmol) of 1,1,2,2,3,3,4,4,4-nonafluoro-N-(1-(4-methoxyphenyl)vinyl)-N-phenylbutane-1-sulfonamide, 145.5 mg (0.586 mmol, 2.5 equiv) of 2,4,6-tri-tert-butylpyrimidine (TTBP), and 11.8 mg (0.05 mmol) of 2,2'-azobis(isobutyrate)dimethyl (V-601) were added thereto and substituted with nitrogen. Next, 2 mL of 1,2-dichloroethane and 0.08 mL (0.47 mmol, 2.0 equiv) of Tf ₂ O were added and stirred for 3 hours while heating at 80°C. After stirring to room temperature, 10 mL of 1 M hydrochloric acid was added and stirred for 30 minutes. It was then extracted with dichloromethane and dehydrated with sodium sulfate. It was transferred to a one-necked eggplant flask and concentrated. 10.1 mg (0.09 mmol) of 1,1,2,2-tetrachloroethane was added as an internal standard and NMR measurement was performed. The yield was calculated from the obtained integral ratio, and the target product 1,1,1-trifluoro-N-(3,3,4,4,5,5,6,6,6-nonafluoro-1-(4-methoxyphenyl)-1-hexen-1-yl)-N-phenylmethanesulfonamide (71%) and the raw material 1,1,2,2,3,3,4,4,4-nonafluoro-N-(1-(4-methoxyphenyl)vinyl)-N-phenylbutane-1-sulfonamide (22%) were obtained, respectively. Isolation and purification were carried out by silica gel column chromatography to obtain 71.1 mg (0.124 mmol, 53%) of the target product and 23.8 mg (0.05 mmol, 20%) of the starting material.

1H-NMR (500MHz, CDCl3) δ7.27-7.31 (m, 3H), 7.15-7.19 (m, 4H), 6.78 (d, J = 9.4Hz, 2H), 6.26 (t, J = 13.2Hz, 1H), 5.2 9 (s, 1H), 3.77 (s, 3H), 1.25-1.33 (m, 6H), 0.89 (t, J = 6.9Hz, 4H); 19F-NMR (471MHz, CDCl3) δ-72.73--72.69 (m, 3F), -81.02--80.97 (m, 3F), -104.97--104.97 (m, 2F), -123.89--123.87 (m, 2F), -125.74--125.69 (m, 2F)
[Example 11]

Examination of the number of equivalents The number of equivalents of Tf ₂ O relative to the imine was examined as shown in Table 2. The reaction was carried out in the same manner as in Example 1, except for the amounts of Tf ₂ O and 2,4,6-tri-tert-butylpyrimidine (TTBP) used.

From the results here, when the amount of Tf ₂ O relative to the imine was 1.1 molar equivalents or more, the target product, 1,1,1-trifluoro-N-phenyl-N-3,3,3-trifluoro-1-(4-methoxyphenyl)-1-propen-1-yl)methanesulfonamide (compound 2 in Table 2) was confirmed.

The manufacturing method of the present invention makes it possible to easily synthesize fluoroalkyl-substituted vinyl fluoroalkanesulfonylamides such as perfluoroalkyl-substituted vinyl perfluoroalkanesulfonylamides, for which no synthesis method has been established until now, and can contribute to the development of pharmaceuticals, agricultural chemicals, etc. Therefore, the present invention has extremely high applicability in the pharmaceutical and agricultural chemical fields.

Claims (4)

A method for producing a fluoroalkyl-substituted vinyl fluoroalkanesulfonylamide, comprising reacting a radical initiator in the presence of an imine or an N-fluoroalkylsulfonylenamine, a fluoroalkylsulfonic anhydride in an amount greater than 1 molar equivalent relative to the imine or N-fluoroalkylsulfonylenamine, and a base in an amount greater than 1 molar equivalent relative to the imine or N-fluoroalkylsulfonylenamine,
The imine is represented by the following formula (1):
(wherein R ¹ and R ² represent an aromatic hydrocarbon group which may have a substituent),
The N-fluoroalkylsulfonylenamine is represented by the following formula (2):
(wherein R ¹ and R ² are defined the same as R ¹ and R ² in formula (1) , and R ^f represents a C ₁ -C ₁₀ fluoroalkyl group);
The base is selected from the organic bases triethylamine, diisopropylethylamine, pyridine, 2,6-lutidine, 2,6-dichloropyridine, 2,4,6-trimethylpyridine, 2,4,6-tri-tert-butylpyridine, 2,6-di-tert-butyl-4-methylpyridine, 2,6-di-tert-butylpyridine or 2,4,6-tri-tert-butylpyrimidine;
The manufacturing method. The fluoroalkylsulfonic anhydride is represented by the following formula (3):
(R ^f SO ₂ ) ₂ O (3)
The method according to claim 1 , wherein R ^f represents a C ₁ -C ₁₀ fluoroalkyl group. The process according to claim 1 or 2 , wherein the base is selected from the group consisting of 2,6-di-tert-butylpyridine and 2,4,6-tri-tert-butylpyrimidine. The process according to any one of claims 1 to 3 , wherein the radical initiator is selected from the group consisting of azobisisobutyronitrile and 2,2'-azobis(isobutyrate)dimethyl.