JP2000034239A - Production of trifluoromethylated aromatic compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce the subject compound easy in supplying its raw material and useful for producing medicines, etc., with a slight production of by-products, and high in purity and yield, by reacting a specific iodinated aromatic compound with a specified compound in the presence of copper bromide, etc., and trifluoromethylating the iodine atoms. SOLUTION: An iodinated aromatic compound in which iodine atoms are bonded to one or more carbon atoms forming an aromatic ring such as a compound represented by formula I or II (n) is 1-6; (m) is 0-5; [(m)+(n)] is 6; R2 is H, a 1-5C alkyl or the like; (k) is 1-4; (p) is 0-3; [(k)+(p)] is 4; R3 is R2} is reacted with a compound represented by the formula FSO2CF2COOR1 (R1 is a 1-5C alkyl) in the presence of copper (I) bromide and 1-methyl-2-pyrrolidone to trifluoromethylate the iodine atoms. Thereby, a trifuloromethylated aromatic compound such as a compound represented by formula III or IV is produced.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing a trifluoromethylated aromatic compound useful as a pharmaceutical, agricultural chemical, or other functional material.

[0002]

2. Description of the Related Art Trifluoromethylated aromatic compounds such as trifluoromethylated benzene derivatives and trifluoromethylated thiophene derivatives are compounds useful as pharmaceuticals, agricultural chemicals, and other functional materials. An introduction method has been developed.

[0003] For example, trifluoromethyluracil derivatives are expected to be useful as pharmaceuticals, particularly as anticancer agents and antiviral agents. Examples of the synthesis include (1) a method in which an iodouridine derivative is reacted with CF ₃ Br in the presence of metallic copper (Japanese Patent Laid-Open No. 2-72190), and (2) a method in which an iodouridine derivative and CF ₃ I are mixed with metallic copper. (Kobayashi, J. Chem. Soc. Perkin Trans.,
1,2755-2761 (1980)), (3) CF ₃ N
(N → O) Method of introducing —CF ₃ group by reacting SO ₂ CF ₃ (Umemoto, Bull. Chem. Soc. Japan., 59, 447-452 (198
6)) and (4) uridine derivative, trifluoroacetic acid-X
Method of reacting eF ₂ to introduce a —CF ₃ group (Tanabe, J.
Org. Chem., 53, 4582-4585 (1988)) and the like.

As a method for synthesizing a trifluoromethylated aromatic compound, (5) a method of reacting an aromatic halide with methyl chlorodifluoroacetate in the presence of potassium fluoride and CuI (I) (Burton , MacNe
il, J. Fluorine Chem., 55, 225 (1991).
61,279 (1993)), (6) aromatic halides and FSO ₂
A method of reacting CF ₂ COOR in dimethylformamide, dimethyl sulfoxide, or p-dinitrobenzene in the presence of CuI (I) (J. Chem. Soc. Chem. Commu.
n., (1989) 705) (7) 2,4,5-trifluoro-3-
Iodobenzoic acid esters and FSO ₂ CF ₂ COOR
A method of reacting in dimethylformamide or dimethylacetamide in the presence of copper (I) iodide
-114711) is known.

[0005]

However, in the conventional synthesis method, as an industrial production method, the reaction is not easy, the reproducibility is poor, the raw material is difficult to procure, the by-products are generated and the yield is low. There was a problem. Further, in the method using copper (I) iodide, the copper (I) iodide is relatively expensive and has low compatibility with the reaction system. Was. In addition, the reaction using copper (I) iodide has a problem that the reaction time becomes long.

According to the present invention, the reaction is simple, the raw material can be easily obtained, the yield is high, the generation of by-products is small, and the use amount of the copper catalyst is small. It is an object of the present invention to provide a novel method for producing a trifluoromethylated aromatic compound.

[0007]

SUMMARY OF THE INVENTION The present invention has been made to solve the above problems. That is, the present invention provides a method for converting an iodide aromatic compound having an iodine atom bonded to at least one of carbon atoms forming an aromatic ring in the presence of copper (I) bromide and 1-methyl-2-pyrrolidone. A method for producing a trifluoromethylated aromatic compound, characterized by reacting to obtain a trifluoromethylated aromatic compound in which the iodine atom is trifluoromethylated.

FSO ₂ CF ₂ COOR ¹ Formula 1 wherein R ^{1 in} Formula 1 represents an alkyl group having 1 to 5 carbon atoms.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION In the following description, a compound represented by the following formula 1 is referred to as “compound 1”. The same applies to other compounds.

[0010] The aromatic ring in this specification refers to an aromatic ring in a broad sense which is not limited to a benzene ring. The aromatic ring may be a ring consisting of only carbon atoms and hydrogen atoms, or a ring consisting of carbon atoms, hydrogen atoms and hetero atoms. As the hetero atom, a nitrogen atom, an oxygen atom and a sulfur atom are preferable, and a sulfur atom is particularly preferable. The aromatic ring in the present invention is preferably a single ring, particularly preferably a benzene ring, a pyridine ring, a thiophene ring, a naphthalene ring or a furan ring, and particularly preferably a benzene ring or a thiophene ring.

The aromatic iodide compound in the present invention refers to a compound in which one or more iodine atoms are bonded to a carbon atom forming the above-mentioned aromatic ring, and one or two iodine atoms are bonded thereto. Compounds are preferred. In the aromatic iodide compound, a substituent other than a hydrogen atom may be bonded to a carbon atom forming a ring. Here, as the substituent, a group containing no halogen atom is preferable, and a hydrocarbon group or a hetero atom-containing group is preferable from the viewpoint of reactivity described below.

The iodinated aromatic compound of the present invention includes iodine having at least one carbon atom forming a ring of a benzene ring to which an iodine atom is bonded and another carbon atom to which a hydrogen atom and / or a substituent are bonded. A benzene compound or a thiophene iodide compound in which an iodine atom is bonded to one or more carbon atoms forming a ring of a thiophene ring and a hydrogen atom and / or a substituent is bonded to another carbon atom is preferable.

As the iodide benzene compound, a compound represented by the following formula 2 is preferable.

[0014]

Embedded image However, the symbols in the formula have the following meanings. n: an integer from 1 to 6. m: an integer from 0 to 5 and m + n = 6. R ² : a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, or a monovalent substituent having a hetero atom, and when m is 2 or more, R ² may be the same or different .

Further, as the thiophene iodide compound,
The compound represented by the following formula 4 is preferred.

[0016]

Embedded image However, the symbols in the formula have the following meanings. k: an integer from 1 to 4. p: an integer of 0 to 3 and k + p = 4. R ³ : a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, or a monovalent substituent having a hetero atom, and when p is 2 or more, R ³ may be the same or different .

R in the iodobenzene compound (formula 2)
² and R ³ in the thiophene iodide compound (Formula 4)
Is a hydrogen atom, an alkyl group having 1 to 5 carbon atoms,
Or a monovalent substituent having a hetero atom.

When R ² and R ³ are each an alkyl group having 1 to 5 carbon atoms, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl or sec-butyl Groups are preferred, especially methyl or ethyl groups. When R ² and R ³ are each a monovalent substituent having a hetero atom, a hydroxyl group, a hydroxyl group with a protective group, an alkoxy group, a substituted alkoxy group, a nitro group, an amino group, an amino group with a protective group Group,
A mercapto group, a protected mercapto group, a carboxyl group, an alkoxycarbonyl group, or a group containing a hetero atom represented by the following formula 6 is preferable.

R ⁴ —X—C (R ⁵ ) (R ⁶ ) — Formula 6 where the symbols in the formula 6 have the following meanings. X: represents a heteroatom and represents -O-, -S- or -NH-
Is preferred. R ^{4 is a} hydrogen atom or an alkyl group having 1 to 5 carbon atoms. When X is -O-, a protecting group for a hydroxyl group;
When X is -S-, it may be a protecting group for a mercapto group, and when X is -NH-, it may be a protecting group for an amino group. R ⁵ and R ⁶ may be the same or different, and each is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms. The alkyl group is preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an n-pentyl group, or a sec-butyl group.

R ² and R ³ in Formula 2 or Formula ³ are
When each is a hydroxyl group having a protecting group, specific examples of the protecting group include an acetyl group, an acyl group (such as an n-propionyl group, a pivaloyl group, a benzoyl group, and a p-phenylbenzoyl group), a benzyl group, and a p-phenylbenzoyl group. -Methoxybenzyl group, trityl group, 4,4'-dimethoxytrityl group, methoxyethoxymethyl group, aryloxycarbonyl group, tetrahydrofuranyl group, methyl group, t-butyl group, trimethylsilyl group, t-butyldimethylsilyl group, Examples thereof include an isopropylsilyl group and a diphenylmethylsilyl group, and a tetrahydrofuranyl group and an acetyl group are preferable.

When R ² and R ³ are each an alkoxy group or a substituted alkoxy group, a methoxy group, an ethoxy group, a propyloxy group, an (isopropyl) oxy group, a butoxy group, an (isobutyl) oxy group, a (t-butyl) group ) An oxy group, a (pentyl) oxy group, a (benzyl) oxy group or a (p-methoxybenzyl) oxy group is preferred, and a methoxy group is particularly preferred.

When two alkoxy groups are present in the formula (2) or (4), the alkyl portion of the alkoxy group may be bonded to form a ring.

When R ² and R ³ are each an amino group having a protecting group, the group is a group in which one or two hydrogen atoms of the amino group have been substituted with a protecting group. Examples of the protecting group include an acetyl group, an n-propionyl group, a pivaloyl group, a benzoyl group, a p-phenylbenzoyl group, a benzyl group, a p-methoxybenzyl group, a trityl group,
Examples include a 4'-dimethoxytrityl group, a methoxyethoxymethyl group, an aryloxycarbonyl group, a benzyloxycarbonyl group, and a t-butoxycarbonyl group.

When R ² and R ³ are each a mercapto group having a protective group, the group is a group in which a hydrogen atom of the mercapto group is substituted with a protective group. Specific examples of the protecting group are preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a t-butyl group, a pentyl group, a benzyl group or a p-methoxybenzyl group. Particularly, a methyl group is preferable.

When R ² and R ³ are each an alkoxycarbonyl group, the group is preferably a group represented by the following formula 7. Here, R ^{7 in} Formula 7 represents an alkyl group having 1 to 5 carbon atoms.

-COOR ⁷ Formula 7 R ⁷ represents a methyl group, an ethyl group, an n-propyl group,
An isopropyl group, an n-butyl group, an n-pentyl group or a sec-butyl group is preferred.

In the group containing a hetero atom represented by the formula 6, R ⁴ is a protecting group for a hydroxyl group, a protecting group for a mercapto group,
Alternatively, when the protective group is an amino group, the protective group includes an acetyl group, an acyl group (such as an n-propionyl group, a pivaloyl group, a benzoyl group or a p-phenylbenzoyl group), a benzyl group, and a p-methoxybenzyl group. , Trityl, 4,4′-dimethoxytrityl, methoxyethoxymethyl, aryloxycarbonyl, tetrahydrofuranyl, methyl, t-butyl, trimethylsilyl, t-butyldimethylsilyl, triisopropylsilyl or And a diphenylmethylsilyl group.

When R ⁵ and R ^{6 in} Formula 6 are each an alkyl group having 1 to 5 carbon atoms, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group,
An n-pentyl group or a sec-butyl group is preferred.

When R ^{2 in} Formula ² and R ^{3 in} Formula 3 are each a monovalent substituent having a hetero atom, an alkoxy group or a nitro group is preferable.

In the formula 2, n is preferably 1 or 2, and particularly preferably 1. That is, as the compound (formula 2), a monoiodinated benzene compound is preferable. When Formula 2 is a monoiodinated benzene compound, five R ^{2 s} are all hydrogen atoms, or three to four hydrogen atoms and the remaining one to two alkyl groups having 1 to 5 carbon atoms. If it is a monovalent substituent containing a group or a heteroatom, is preferred.

Specific examples of the formula 2 include the following compounds.

Iodobenzene, 4-methyliodobenzene, 4-methoxyiodobenzene, 4-nitroiodobenzene.

In the formula 4, k is preferably 1 or 2. That is, Formula 4 is preferably thiophene monoiodide or thiophene diiodide. When Formula 4 is thiophene monoiodide or thiophene diiodide, 2-3 R ³ preferably contain one or more hydrogen atoms, and when all are hydrogen atoms, or when hydrogen atoms and hydrogen atoms and In the case where it is composed of an alkyl group or a monovalent substituent containing a hetero atom of from 5 to 5, it is preferable.

Specific examples of Formula 4 include the following compounds.

2-iodothiophene, 5-methyl-2-
Iodothiophene, 3-methyl-2-iodothiophene, 2,5-diiodothiophene.

In the present invention, the aromatic iodide compound is reacted with the compound (formula 1) in the presence of copper (I) bromide and 1-methyl-pyrrolidone.

R ¹ in the compound (formula 1) has 1 to 5 carbon atoms.
And a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an n-pentyl group or a sec-butyl group is preferred, and a methyl group is particularly preferred. As the compound (formula 1), methyl 2,2-difluoro- (fluorosulfonyl) acetate is preferable.
The amount of the compound (formula 1) is preferably from 0.1 to 50 times, more preferably from 1 to 10 times, the moles of the iodinated aromatic compound.

As the copper (I) bromide, commercially available copper (I) bromide can be used and has a purity of 95 to 99.9999.
%, And may be purified before the reaction to improve the purity. In the present invention, the use of copper bromide is essential.
Copper bromide has a higher solubility in the reaction system than other copper halides (copper iodide), so that the amount of copper bromide can be reduced. Further, the yield of the reaction is high, and the generation of by-products can be reduced. The amount of copper (I) bromide is preferably from 0.0001 to 100 times, more preferably from 0.001 to 10 times, the weight of the aromatic iodide compound.

In the present invention, 1-methyl-2-pyrrolidone (hereinafter, referred to as NMP) is also essential. NMP
Has high solubility of copper bromide. Further, by using NMP, the yield can be increased and the generation of by-products can be reduced as compared with the case where a conventional aprotic solvent is used. The amount of NMP is 0.1 to 1000 with respect to the iodinated aromatic compound.
Double weight is preferable, and 1 to 200 times weight is particularly preferable.
NMP can be used after being dried by a method such as molecular sieves or distillation before use.

In the reaction according to the present invention, the iodine atom in the iodinated aromatic compound is replaced by a trifluoromethyl group. The pressure for this trifluoromethylation reaction is not limited, and normal pressure is preferred from the viewpoint of workability. The reaction temperature is 110 ° C
~ 130 ° C is preferred. If the reaction temperature is too high or too low, the yield may decrease. The reaction time is 0.1
-100 hours, preferably 0.5-50 hours, particularly preferably 0.5-3 hours. The method of the present invention can be sufficiently carried out even if the reaction time is within 3 hours. Further, the trifluoromethylation reaction is preferably performed in an atmosphere of an inert gas such as argon or nitrogen.

In the reaction of the present invention, a trifluoromethylated aromatic compound is obtained in which the iodine atom of the iodinated aromatic compound is trifluoromethylated. When the compound (Formula 2) is used as the iodinated aromatic compound, a compound (Formula 3) is produced, and when the compound (Formula 4) is used, the compound (Formula 5) is produced.

[0042]

Embedded image

Embedded image

However, the symbols in Formulas 3 and 5 have the same meanings as in Formulas 2 and 4, respectively.
In Formula 3, CF ₃ is present at a position corresponding to the bond position of I in Formula 2, and the same R ² is present at the same bond position as R ² in Formula 2. In equation 5, I of equation 4
CF ₃ is present at a position corresponding to the bonding position of, and the same R ² is present at the same bonding position as R ² in Formula 4.

Specific examples of the compound (Formula 3) include the following compounds.

Trifluoromethylbenzene, 4-methyl-trifluoromethylbenzene, 4-methoxy-trifluoromethylbenzene, 4-nitro-trifluoromethylbenzene.

Specific examples of the compound (Formula 5) include the following compounds.

2-trifluoromethylthiophene, 5-
Methyl-2-trifluoromethylthiophene, 3-methyl-2-trifluoromethylthiophene, 2,5-bis (trifluoromethyl) thiophene.

The trifluoromethylated aromatic compound obtained by the present invention may be added to a protected group such as a protected amino group, a protected mercapto group, or a protected hydroxyl group. Is present, a deprotection reaction may be performed as necessary. When an alkoxycarbonyl group is present, it may be converted to a carboxyl group by hydrolysis or the like. As the method and conditions of the deprotection reaction, the methods and conditions in a usual organic synthesis method can be employed as they are.

When the obtained trifluoromethylated aromatic compound is desired to be highly purified, it may be purified. Examples of the purification method include a recrystallization method, a distillation method, a chromatographic method, a method based on a combination thereof, and the like. The trifluoromethylated aromatic compound produced according to the present invention is useful as a medicine, an agricultural chemical, other functional materials, or as a raw material thereof.

[0050]

[Examples] [Examples 1 to 9] Iodide aromatic compounds in Table 1
(0.020 mol), FSO_TwoCF_TwoCOOCH
_Three(5.76 g, 0.030 mol) dried NM
P (20 ml), and copper (I) bromide (0.34 g,
0.00024 mol) at 120 ° C. in a nitrogen atmosphere.
Was reacted. Gas chromatography for the progress of the reaction
The reaction was carried out for 2 hours while confirming with a mouse. Conversion rate rises
Water (20 ml) was added and steam distilled.
Was. The aqueous layer of the fraction was extracted with ether and the ether was extracted.
After mixing the organic layer and the organic layer,
Obtaining the trifluoromethylated aromatic compound in Table 1
Was. The above reaction was performed on the starting compounds of Examples 1 to 9 in Table 1.
The conversion and yield are shown in Table 1. What
In Example 9, 2,5-diiodide thiophene
FSO_TwoCF_TwoCOOCH_Three3 equivalents of copper (I) bromide
Was used in 0.25 equivalents.

[0051]

[Table 1] The spectrum data of the trifluoromethylated aromatic compounds obtained in Examples 1 to 9 are shown below.

Example 1 Trifluoromethylbenzene bp (760 mmHg) = 100-102 ° C. ¹ H-NMR (CDCl ₃ ) δ _H (ppm): 7.42-7.75 (m, aromatics proton
s). ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ) δ _F (ppm): -62.6 (s, C F ₃ ). ¹³ C-NMR (CDCl ₃ ) δ _C (ppm): 124.2 (q, C F ₃ , ¹ J _CF = 270 Hz), 1
25.2 (q, C H, J _CF = 4.0Hz), 128.8 (s, C H), 130.5 (q, C -CF ₃ , ² J
_{CF = 45Hz), 131.8 (q} , C H, J CF = 1Hz), MS m / z (EIMS): 146 (M +, 100), 127 (M + -F, 95).

[0053] [Example 2] 4-methyl - trifluoromethylbenzene bp (760 mmHg) = 128-130 ℃ 1 H-NMR (CDCl 3) δ H (ppm): 2.43 (3H, s, C H 3), 7.28 (2H, d, C H ,
_{^{. 3 J HH = 8.0Hz),}} 7.53 (2H, d, C H, 3 J HH = 8.0Hz) 19 F-NMR (CDCl 3, CFCl 3) δ F (ppm): - 62.2 (s, C F 3 ). ¹³ C-NMR (CDCl ₃ ) δ _C (ppm): 21.2 (s, C H ₃ ), 124.5 (q, C F ₃ , ¹ J
_{CF = 270Hz), 125.2 (s} , C H), 127.9 (q, C -CF 3, 2 J CF = 32Hz), 12
9.5 (s, C H), 142.1 (s, C -CH 3) MS m / z (EIMS):. 160 (M +, 78), 141 (M + -F, 32).

[0054] [Example 3] 4-Methoxy - trifluoromethylbenzene bp (760 mmHg) = 166-168 ℃ 1 H-NMR (CDCl 3) δ H (ppm): 3.85 (3H, s, C H 3), 6.98 (2H, d, C H ,
_{^{. 3 J HH = 8.0 Hz)}} , 7.57 (2H, d, C H, 3 J HH = 8.0Hz) 19 F-NMR (CDCl 3, CFCl 3) δ F (ppm): - 61.4 (s, C F 3 ). ¹³ C-NMR (CDCl ₃ ) δ _C (ppm): 55.3 (s, O C H ₃ ), 113.8 (s, C H), 12
_{2.8 (q, C -CF 3,} 2 J CF = 34Hz), 126.8 (q, C H, 4 J CF = 4 Hz), 161.9
(s, C -OCH ₃ ), Not seen CF ₃ .MS m / z (EIMS): 176 (M ⁺ , 100), 157 (M ⁺ -F, 44).

Example 4 4-nitro-trifluoromethyl
Benzene m.p. = 37-39 ℃¹ H-NMR (CDCl_Three) δ_H(ppm): 7.84 (2H, d, CH,^ThreeJ_HH= 9.0Hz), 8.3
6 (2H, d, CH,^ThreeJ_HH= 9.0 Hz).¹⁹ F-NMR (CDCl_Three, CFCl_Three) δ_F(ppm): -63.1 (s, CF _Three).¹³ C-NMR (CDCl_Three) δ_C(ppm): 124.1 (s,CH), 126.8 (q,CH,^FourJ
_CF= 4 Hz), 136.1 (q,C-CF_Three, ^TwoJ_CF= 32Hz), Not seenCF_Three and
 C-NO_Two.MS m / z (EIMS): 191 (M⁺, 65), 172 (M⁺-F, 10), 145
(M⁺-NO_Two, 100).

Example 5 2-methyl-3-nitro-trifluoromethylbenzene bp (760 mmHg) = 188-190 ° C. ¹ H-NMR (CDCl ₃ ) δ _H (ppm): 2.54 (3H, q, C H ₃ , ⁵ J _HF = 1.5 Hz), 7.
46 (1H, dd, C H , ³ J _HH = 8.2Hz, ³ J _HH = 7.8Hz), 7.85 (1H, d, C H , ³ J
_HH = 7.8 Hz), 7.89 (1 H, d, C H , ³ J _HH = 8.2 Hz). ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ) δ _F (ppm): -60.7 (s, C F ₃ ). ¹³ C-NMR (CDCl ₃ ) δ _C (ppm): 14.6 (s, C H ₃ ), 123.4 (q, C F ₃ , ¹ J
_CF = 270 Hz), 126.8 (s, C H), 127.1 (s, C H), 129.5 (q, C H, ³ J _CF
= 6Hz), 131.3 (s, C -CH 3), 131.4 (q, C -CF 3, 2 J CF = 34Hz), 152.
_{. 1 (s, C -NO 2} ) MS m / z (EIMS): 205 (M +, 12), 188 (M + -OH, 100), 160 (M + -N
O ₂ , 37).

Example 6 2-trifluoromethylthiophene
B.p. (760 mmHg) = 93-95 ° C¹ H-NMR (CDCl_Three) δ_H(ppm): 7.07 (1H, ddq, Hb,^ThreeJ_HbHa= 3.7Hz,
^ThreeJ_HbHc= 4.8Hz,^FiveJH_bF= 1.1Hz), 7.46 (1H, ddq, Ha,^ThreeJ_HaHb= 3.
7Hz,^FourJ_HaHc= 1.1Hz,^FourJ_HaF= 1.1Hz), 7.50 (1H, dd, Hc, ^ThreeJ_HcHb
= 4.8Hz,^FourJ_HcHa= 1.1Hz).¹⁹ F-NMR (CDCl_Three, CFCl_Three) δ_F(ppm): -55.0 (s, CF _Three).¹³ C-NMR (CDCl_Three) δ_C(ppm): 122.7 (q, CF_Three,¹J_CF= 269Hz), 12
7.0 (s,CH), 128.7 (s,CH), 128.9 (s,CH), 131.4 (q,C-CF_Three,^TwoJ
_CF= 38Hz) .MS m / z (EIMS): 152 (M⁺, 50), 133 (M⁺-F, 45).

[0058] [Example 7] 5-methyl-2-trifluoromethyl-thiophene bp (760 mmHg) = 120 ℃ 1 H-NMR (CDCl 3) δ H (ppm): 2.52 (3H, s, C H 3), 6.72 (1H, dq, C
H , ³ J _HH = 3.6 Hz, ⁴ J _HF = 1.5 Hz), 7.23 (1H, dq, C H , ³ J _HH = 3.6 Hz,
⁴ J _HH = 1.1 Hz). ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ) δF (ppm): -55.2 (s, C F 3). ¹³ C-NMR (CDCl ₃ ) δ _C (ppm): 15.1 (s, C H ₃ ), 122.6 (q, CF ₃ , ¹ J
_CF = 268 Hz), 125.1 (s, C H), 128.5 (q, C -CF ₃ , ² J _CF = 34 Hz), 12
8.6 (q, C H, ⁴ J _CF = 4 Hz), 144.3 (q, C -CH ₃ , ⁴ J _CF = 1 Hz) .MS m / z (EIMS): 166 (M ⁺ , 100), 147 (M ⁺ -F, 20).

[0059] [Example 8] 3-methyl-2-trifluoromethyl-thiophene bp (760 mmHg) = 120-122 ℃ 1 H-NMR (CDCl 3) δ H (ppm): 2.35 (3H, q, C H 3 , ⁵ J _HF = 1.8Hz), 6.
86 (1H, dq, C H , ³ J _HH = 5.0 Hz, ⁴ J _HF = 0.9 Hz), 7.30 (1 H, d, C H , ³ J
_HH = 5.06 Hz). ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ) δ _F (ppm): -54.3 (s, C F ₃ ). ¹³ C-NMR (CDCl ₃ ) δ _C (ppm): 13.9 (s, C H ₃ ), 123.2 (q, C F ₃ , ¹ J
_CF = 269Hz), 125.0 (q, C -CF ₃ , ² J _CF = 38Hz), 126.6 (q, C H, ⁴ J _CF
= 2 Hz), 131.2 (s , C H), 140.0 (q, C -CH 3, 3 J CF = 3Hz) MS m / z (EIMS): 166 (M +, 100), 147 (M + -. F, 17).

Example 9 2,5-bis (trifluoromethyl) thiophene bp (760 mmHg) = 95 ° C. ¹ H-NMR (CDCl ₃ ) δ _H (ppm): 7.41 (s, C H ). ¹⁹ F- NMR (CDCl ₃ , CFCl ₃ ) δ _F (ppm): -55.8 (s, C F ₃ ). ¹³ C-NMR (CDCl ₃ ) δ _C (ppm): 128.2 (s, C H): Not seen, C -CF ₃
and C F ₃ .

[0061]

According to the production method of the present invention, easily available raw materials can be used without using special reaction procedures and conditions.
The desired trifluoromethylated aromatic compound can be synthesized. The method of the present invention can be carried out in a short time, is suitable for large-volume production, has good reproducibility of the reaction, and suppresses the generation of by-products, and is therefore useful as an industrial production method.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Alison Jay Foster Birmingham B15 2TT, England, University of Birmingham, University of Birmingham, School of Chemistry F-term (reference) 4H006 AA02 AC22 AC30 BA05 BA37 BB24 BC10

Claims (5)

[Claims] 1. An aromatic iodide compound having an iodine atom bonded to at least one of carbon atoms forming an aromatic ring is reacted with copper (I) bromide and 1-methyl-2-pyrrolidone in the presence of A method for producing a trifluoromethylated aromatic compound, which comprises reacting the compound with the compound represented by Formula 1 to obtain a trifluoromethylated aromatic compound in which the iodine atom is trifluoromethylated. FSO ₂ CF ₂ COOR ¹ Formula 1 wherein R ^{1 in} Formula 1 represents an alkyl group having 1 to 5 carbon atoms. 2. An iodinated aromatic compound is a benzene iodide compound and a trifluoromethylated aromatic compound is a trifluoromethylbenzene compound, or an iodinated aromatic compound is a thiophene iodide compound and trifluoromethyl The production method according to claim 1, wherein the fluorinated aromatic compound is a trifluoromethylthiophene compound. 3. The iodinated aromatic compound is an iodinated benzene compound represented by the following formula 2, and the trifluoromethylated aromatic compound is a trifluoromethylated benzene derivative represented by the following formula 3. 2. The production method according to 1. Embedded image Embedded image However, the symbols in the formula have the following meanings. In Formula 3, CF is located at a position corresponding to the bonding position of I in Formula 2.
₃ is present, and at the same bond position as R ² in Formula 2, the same R ²
Exists. n: an integer from 1 to 6. m: an integer from 0 to 5 and m + n = 6. R ² : a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, or a monovalent substituent having a hetero atom, and when m is 2 or more, R ² may be the same or different . 4. An iodinated aromatic compound is a thiophene iodide compound represented by the following formula (4), and a trifluoromethylated aromatic compound is a trifluoromethylated thiophene compound represented by the following formula (5). 2. The production method according to 1. Embedded image Embedded image However, the symbols in the formula have the following meanings. In addition, in Formula 5, CF at the position corresponding to the bonding position of I in Formula 4
₃ is present, and at the same bonding position as R ³ in Formula 4, the same R ³
Exists. k: an integer from 1 to 4. p: an integer of 0 to 3 and k + p = 4. R ³ : a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, or a monovalent substituent having a hetero atom, and when p is 2 or more, R ³ may be the same or different . 5. The method according to claim 1, wherein the reaction temperature is 110 ° C. to 130 ° C.