KR100530345B1 - Method for preparing amine compound from nitro compound using indium metal wire - Google Patents

Abstract

The present invention relates to a method for reducing the nitro compound represented by the following formula (1) to an amine compound represented by the formula (2) at room temperature and in an aqueous solution using an indium metal wire, wherein R represents an aliphatic or aromatic compound.

[Formula 1]

[Formula 2]

Description

METHOD FOR PREPARING AMINE COMPOUND FROM NITRO COMPOUND USING INDIUM METAL WIRE}

The present invention relates to a method for preparing an amine compound by reducing an aliphatic or aromatic nitro compound using an indium metal.

Reactions to reduce nitro groups to amine groups are well known. Examples of commonly known methods include SmI ₂ ( Tetrahedron Lett ., 1991 , 32 , 1699), Cu (acac) ₂ ( J. Chem. Soc., Perkin trans, 1 , 1979 , 2409), Ni (OAc) ₂ ( Synlett ., 1993 , 135), In ( Synlett ., 1998 , 1028), LiAlH ₄ ( J. Am. Chem. Soc . 1952 , 74 , 1837), H ₂ / PtO ₂ ( Bull. Chem. Soc. Jpn . 1960 , 34 , 32), etc. can be mentioned.

However, these methods require vigorous reaction conditions such as using hydrogen or other flammable materials as reactants, or refluxing the solvent.

The inventors have found that when indium metal is used, the nitro group can be reduced to the amine group under mild conditions. The aliphatic or aromatic nitro compound can be converted into an amine compound in an aqueous organic solvent using an indium metal and an acid as a catalyst. A method of reducing has been filed as a patent (Korean Patent Application No. 2000-21258).

However, even the method of reduction under mild conditions such as shown in Scheme 1 below, in which nitrobenzene is reduced to aminobenzene using an indium powder and an acid catalyst in room temperature and aqueous tetrahydrofuran in aqueous solution, increases the reaction scale. Since the powder shows a problem of agglomeration with each other, it is necessary to improve it.

The object of the present invention is not only to prevent the aggregation of indium metal that occurs when the indium metal powder is used even if the reaction scale is large, but also to reduce the nitro compound to the amine compound under milder conditions than conventional methods. To provide a new way.

The object of the present invention as described above can be achieved by performing a reduction reaction of the nitro compound in an aqueous solution using an indium metal wire. That is, the inventors of the present invention, when the nitro group present in the aliphatic or aromatic nitro compound is reduced in an aqueous solution using an indium metal wire, even if the reaction scale is large, agglomeration of indium metal does not occur, and in the case of using indium in powder form It has been found that a small amount of indium metal is consumed compared to the present invention, thus completing the present invention.

Accordingly, the present invention provides a method for producing an amine compound represented by the formula (2) by reducing the aliphatic or aromatic nitro compound represented by the following formula (1) using an indium metal wire in an aqueous solution.

In Formulas 1 and 2, R represents an aliphatic or aromatic compound, which may have a double bond in the molecular structure, or may be substituted by a hydroxy group, a halogen atom, an ester group and the like.

The amount of indium metal consumed in the reduction reaction according to the invention is in the range of 1-3.5 equivalents, preferably 1.5-2.5 equivalents, and most preferably 1.5-2.0 equivalents per nitro group. The amount of indium consumed in this range is smaller than that of using indium metal in powder form, and since the indium metal is expensive, the present invention is more economical than the conventional method.

The reduction reaction can be promoted by adding a small amount of acid. The type of acid that can be used as the catalyst is not particularly limited, but it is preferable to use an acid such as hydrochloric acid (HCl) or bromic acid (HBr) which is most commonly used. The amount of acid added to the reactants is not particularly limited as long as the pH of the reaction mixture can be maintained at 1 to 2, which is the range in which the metal surface can be activated.

Performing the reduction reaction in an aqueous solution means using only water as the reaction solvent without adding other organic solvents. At this time, since the nitro compound to be reduced has low solubility in water, it may be desirable to sonicate the reaction mixture to promote the reaction by increasing the contact area between the nitro compound and the indium metal. On the other hand, the reaction temperature is controlled in the range of 0-30 占 폚, preferably 20-25 占 폚. The temperature range of 20-25 ° C. corresponds to a range recognized by a person of ordinary skill in the art to be “room temperature”.

Example

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the embodiments are only examples of the present invention, and the scope of the present invention is not limited thereto.

Example 1

Preparation of 3,4-difluorophenylamine

473.3 mg (2.97 mmol) of 1,2-difluoro-4-nitrobenzene was placed in a beaker, 1 ml of water and a sufficient amount of indium wire (5.0 g) were placed in a sonicator. Concentrated hydrochloric acid was added to adjust the pH of the reaction mixture to a range of 1-2, and slightly ultrasonically applied at room temperature. After 75 minutes, the remaining indium wire was removed (consumption amount 5.08 mmol), and the pH of the reaction mixture was adjusted to 9-10 by adding an aqueous solution of Na ₂ CO ₃ , and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated under reduced pressure to obtain 350 mg (yield: 91%) of the desired product.

¹ H-NMR (300 MHz) δ: 6.94 (m, 1 H), 6.48 (m, 1 H), 6.35 (m, 1 H), 3.61 (s, -NH ₂ )

Example 2

Preparation of Aniline

505 mg (4.10 mmol) of nitrobenzene were placed in a beaker, 1 ml of water and a sufficient amount of indium wire were placed, and then placed in a sonicator. Concentrated hydrochloric acid was added to adjust the pH of the reaction mixture to a range of 1-2, and slightly ultrasonically applied at room temperature. After 60 minutes, the remaining indium wire was taken out (7.92 mmol of consumed amount), and the reaction mixture was adjusted to 9-10 by adding Na ₂ CO ₃ aqueous solution, and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated under reduced pressure to obtain 359 mg (yield: 94%) of the desired product.

¹ H-NMR (300 MHz) δ: 7.24 (t, 2H), 6.85 (t, 1H), 6.71 (d, 2H), 3.64 (s, -NH ₂ )

Example 3

Preparation of 4-aminobenzyl alcohol

172 mg (1.12 mmol) of 4-nitrobenzyl alcohol were added to the beaker, 1 ml of water and a sufficient amount of indium wire were placed, and then placed in a sonicator. Concentrated hydrochloric acid was added to adjust the pH of the reaction mixture to a range of 1-2, and slightly ultrasonically applied at room temperature. After 15 minutes, the remaining indium wire was taken out (consumption amount 2.27 mmol), an aqueous solution of Na ₂ CO ₃ was added to adjust the pH of the reaction mixture to 9-10, and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated under reduced pressure to obtain 130 mg (yield: 94%) of the desired product.

¹ H-NMR (300 MHz) δ: 7.15 (t, 2H), 6.67 (d, 2H), 4.54 (s, 2H), 3.60 (s, -NH ₂ )

Example 4

Preparation of 1- (4-amino-2-fluorophenyl) pyrrolidin-3-ol

54 mg (0.24 mmol) of 1- (4-nitro-2-fluorophenyl) pyrrolidine-3-ol was placed in a beaker, 1 ml of water and a sufficient amount of indium wire were placed, and then placed in a sonicator. . Concentrated hydrochloric acid was added to adjust the pH of the reaction mixture to a range of 1-2, and slightly ultrasonically applied at room temperature. After 15 minutes, the remaining indium wire was taken out (consumption amount 2.27 mmol), an aqueous solution of Na ₂ CO ₃ was added to adjust the pH of the reaction mixture to 9-10, and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated under reduced pressure to obtain 45 mg (yield: 95%) of the desired product.

¹ H-NMR (300 MHz) δ: 6.57 (m, 1H), 6.40 (m, 2H), 4.45 (m, 1H), 3.48 (m, 1H), 3.37 (m, 1H), 3.12 (m, 6H) , 2.14 (m, 1 H), 1.93 (m, 1 H)

Example 5

Preparation of 4-bromo-3-methylphenylamine

250 mg (1.16 mmol) of 1-bromo-2-methyl-4-nitrobenzene was placed in a beaker, 1 ml of water and a sufficient amount of indium wire were placed, and then placed in a sonicator. Concentrated hydrochloric acid was added to adjust the pH of the reaction mixture to a range of 1-2, and slightly ultrasonically applied at room temperature. After 210 minutes, the remaining indium wire was taken out (consumption amount 2.39 mmol), an aqueous solution of Na ₂ CO ₃ was added to adjust the pH of the reaction mixture to 9-10, and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated under reduced pressure to obtain 210 mg (yield: 98%) of the desired product.

¹ H-NMR (300 MHz) δ: 7.27 (d, 1H), 6.58 (s, 1H), 6.40 (d, m, 1H), 3.60 (s, -NH ₂ ), 2.30 (s, 3H)

Example 6

Preparation of 4-phenyl-3-butenylamine

54 mg (0.30 mmol) of 4-nitro-1-butenylbenzene were placed in a beaker, 1 ml of water and a sufficient amount of indium wire were placed, and then placed in a sonicator. Concentrated hydrochloric acid was added to adjust the pH of the reaction mixture to a range of 1-2, and slightly ultrasonically applied at room temperature. After 65 minutes had elapsed, the remaining indium wire was taken out (0.53 mmol of consumed amount), and the pH of the reaction mixture was adjusted to 9-10 by addition of aqueous Na ₂ CO ₃ solution, and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated under reduced pressure to obtain 33 mg (yield: 85%) of the desired product.

¹ H-NMR (300 MHz) δ: 7.28 (m, 5H), 6.43 (d, 1H), 6.17 (m, 1H), 2.84 (t, 2H), 2.38 (m, 2H, -NH ₂ )

Example 7

Preparation of 2- (2-aminophenyl) ethan-1-ol

203 mg (1.21 mmol) of 2- (2-nitrophenyl) ethan-1-ol was placed in a beaker, 1 ml of water and a sufficient amount of indium wire were placed, and then placed in a sonicator. Concentrated hydrochloric acid was added to adjust the pH of the reaction mixture to a range of 1-2, and slightly ultrasonically applied at room temperature. After 10 minutes, the remaining indium wire was taken out (consumption amount 2.39 mmol), an aqueous solution of Na ₂ CO ₃ was added to adjust the pH of the reaction mixture to 9-10, and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated under reduced pressure to obtain 165 mg (yield: 99%) of the desired product.

¹ H-NMR (300 MHz) δ: 7.03 (m, 2H), 6.74 (t, 1H), 6.66 (d, 1H), 3.81 (t, 2H), 2.73 (t, 2H)

Example 8

Preparation of 3-chloro-phenylamine

82.5 mg (0.52 mmol) of 1-chloro-3-nitrobenzene was added to the beaker, 1 mL of water and a sufficient amount of indium wire were added thereto, and then placed in a sonicator. Concentrated hydrochloric acid was added to adjust the pH of the reaction mixture to a range of 1-2, and slightly ultrasonically applied at room temperature. After 60 minutes, the remaining indium wire was taken out (consumption amount 1.20 mmol), and the pH of the reaction mixture was adjusted to 9-10 by adding an aqueous solution of Na ₂ CO ₃ , and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated under reduced pressure to give 63.3 mg (yield: 95%) of the desired product.

¹ H-NMR (300 MHz) δ: 7.60 (t, 1 H), 6.70 (m, 2 H), 6.54 (d, 1 H), 3.71 (s, -NH ₂ )

Example 9

Preparation of 4- (2-aminophenyl) -but-2-enoic acid ethyl ester

53 mg (0.23 mmol) of 4- (2-nitrophenyl) -but-2-enoic acid ethyl ester was placed in a beaker, 0.5 mL of water and a sufficient amount of indium wire were added thereto, and then placed in a sonicator. Concentrated hydrochloric acid was added to adjust the pH of the reaction mixture to a range of 1-2, and slightly ultrasonically applied at room temperature. After 25 minutes, the remaining indium wire was taken out (consumption amount 0.44 mmol), the pH of the reaction mixture was adjusted to 9-10 by addition of aqueous Na ₂ CO ₃ solution, and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated under reduced pressure to obtain 46 mg (yield: 99%) of the desired product.

¹ H-300 MHz (CDCl ₃ ) δ: 7.19-7.03 (m, 2H), 6.81 (6.53 (m, 2H), 6.18 (m, 1H), 4.19 (m, 2H), 3.72 (s, -NH ₂ ) , 3.44 (d, 1H, J = 8.35), 3.35 (d, 2H, J = 8.26), 1.28 (m, 3H)

Example 10

Preparation of 3-methyl-2-aminophenol

172 mg (1.12 mmol) of 3-methyl-2-nitrophenol was placed in a beaker, 1 ml of water and a sufficient amount of indium wire were placed in a beaker, and then placed in a sonicator. Concentrated hydrochloric acid was added to adjust the pH of the reaction mixture to a range of 1-2, and slightly ultrasonically applied at room temperature. After 3 minutes, the remaining indium wire was taken out (consumption amount 0.44 mmol), an aqueous solution of Na ₂ CO ₃ was added to adjust the pH of the reaction mixture to 9-10, and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The obtained filtrate was concentrated under reduced pressure to obtain 135.5 mg (yield: 98%) of the desired product.

¹ H-300 MHz (CDCl ₃ ) δ: 6.70 (t, 1H), 6.60 (d, 2H), 3.60 (s, -NH ₂ ), 2.20 (s, 3H)

According to the present invention there is provided a method for reducing aliphatic or aromatic nitro compounds to amine compounds in aqueous solution using indium metal wires and acid catalysts. In the present invention, indium metal wires can be prevented from being aggregated by an acid catalyst in a large-scale reaction by using an indium metal wire, and in a short time at room temperature from a nitro compound while using a small amount of indium metal as compared to the conventional method. The amine compound can be obtained in high yield and the process according to the invention has the advantage of being an environmentally friendly manufacturing process since the reaction is carried out in an aqueous solution.

Claims (4)

Method for preparing an amine compound by reducing the nitro compound represented by the following formula (1) while sonicating in an aqueous solution of pH 1-2 using an indium metal wire: [Formula 1] In the formula, R represents an aliphatic or aromatic compound. The method of claim 1 wherein the reduction reaction is carried out in the range of 20-25 ° C. The method of claim 1 wherein the amount of indium metal used is 1.5-2.0 equivalents to one nitro group. The method of claim 1, wherein hydrochloric or bromic acid is added to adjust the pH of the aqueous solution to 1-2.