KR20010097299A - A method for reducing nitro group to amine group using indium - Google Patents

Abstract

The present invention provides a method for reducing a compound having a nitro group (-NO ₂ ) to an amine (-NH ₂ ) compound using an indium metal. More specifically, a method of reducing an aliphatic or aromatic compound having Formula 1 to a compound of Formula 2 using indium metal is provided.

[Formula 1]

[Formula 2]

In Formulas 1 and 2, R represents an aliphatic or aromatic compound, n is an integer of 1-5, preferably an integer of 1-3, most preferably 1 or 2.

The reduction reaction of the present invention using indium metal not only proceeds in a short time at room temperature but also can reduce several nitro groups at once in a short time. In addition, only nitro groups can be selectively reduced without affecting other functional groups in the molecule, and since the reaction proceeds easily in an aqueous solution, it is an environmentally friendly industrial process. Therefore, it can be variously applied in the chemical industry.

Description

Reduction of nitro groups to amine groups using indium {A METHOD FOR REDUCING NITRO GROUP TO AMINE GROUP USING INDIUM}

The present invention relates to a method for reducing a compound having a nitro group (-NO ₂ ) to an amine (-NH ₂ ) compound using an indium metal. More specifically, the present invention relates to a method of reducing an aliphatic or aromatic compound having formula (1) to a compound of formula (2) using indium metal (Scheme 1).

In Formulas 1 and 2, R represents an aliphatic or aromatic compound, n is an integer of 1-5, preferably an integer of 1-3, most preferably 1 or 2.

Reactions to reduce nitro groups to amine groups are well known. Examples of commonly known methods include LiAlH ₄ ( J. Am. Chem. Soc . 1952 , 74 , 1837), H ₂ / PtO ₂ ( Bull. Chem. Soc. Jpn . 1960 , 34 , 32), HCO ₂ H / Cu or Ni ( J. Chem. Soc . 1943 , 281) and N ₂ H ₄ / Raney Nickel ( J. Org. Chem . 1958 , 23 , 680) and the like.

However, these methods require the use of dangerous hydrogen, the use of flammable materials or the intense reaction conditions to reflux the solvent. In addition, the above methods not only reduce the nitro group but also other functional groups in the molecule (for example, double bonds, triple bonds, carbonyl groups, etc.) have the drawback of advancing the reaction. I have a hard time going through a few steps.

For example, using H ₂ / RhCl ( J. Org. Chem. , 1969 , 34 , 3684) in the method of reducing trans-beta nitrostilylene 3 as in Scheme 2 below, instead of reducing the nitro group, Beta-nitroethylbenzene 4 with saturated bonds is obtained, and betaaminoethylbenzene 5 with both nitro and double bonds reduced is obtained using 10% Pd / HCl ( Helv. Chim. Acta 1968 , 51 , 1965). . To date, there is no way to obtain compound 6 which is selectively reduced by only nitro groups.

It is therefore an object of the present invention to provide a new method of reducing nitro groups to ami groups.

Another object of the present invention is to provide a method for selectively reducing nitro groups.

The above and other objects of the present invention can be achieved by a method of reducing a nitro group to an amine group using indium metal.

The inventors have diligently studied how to reduce the nitro group to amine groups under mild conditions and found that this can be achieved when using indium metal. That is, when using indium metal, even if there are other functional groups capable of participating in a reduction reaction such as a double bond in the molecular structure, it was found that only nitro groups to be reduced can be selectively reduced without affecting these functional groups.

Accordingly, the present invention relates to a method for reducing nitro group (-NO ₂ ) to amine group (-NH ₂ ) using indium metal. More specifically, the present invention relates to a method of reducing an aliphatic or aromatic compound having formula (1) to a compound of formula (2) using indium metal (Scheme 1).

[Formula 1]

[Formula 2]

Scheme 1

In Formulas 1 and 2, R represents an aliphatic or aromatic compound, and may be substituted by a double bond, a triple bond, a hydroxyl group, a halogen atom, an ester group, or the like in the molecular structure. n is an integer of 1-5, preferably an integer of 1-3, most preferably 1 or 2.

The amount of indium used in the reduction reaction can be adjusted in the range of 1-6 equivalents, preferably 2-5 equivalents, most preferably 3.5-4.5 equivalents, per one nitro group.

The reduction reaction may promote the reaction by adding a small amount of acid. The kind of acid that can be added to the reaction is not particularly limited, but HCl and HBr which are most widely used are preferred. The amount of acid added to the reaction is not particularly limited and may be added in excess, but preferably about 1-2 equivalents to indium.

The reduction reaction is preferably carried out in an aqueous organic solvent phase. In the present specification, the aqueous organic solvent refers to an organic solvent including water, and examples thereof include alcohols such as tetrahydrofuran, acetonitrile, methanol, ethanol or isopropyl alcohol, and the like.

The reaction temperature of the reduction reaction can be controlled within the range of 0-30 ℃, preferably 20-25 ℃, if there is no other functional group capable of participating in the reduction reaction in the molecule to be reduced to reflux the reaction solution Reaction can be carried out.

Hereinafter, the present invention will be described in more detail with reference to the following examples, but the scope of the present invention is not limited to these examples.

Example 1

Preparation of 3,4-difluorophenylamine

143.7 mg (0.90 mmol) of 1,2-difluoro-4-nitrobenzene were dissolved in 3 ml of 25% aqueous tetrahydrofuran solution, and the resulting solution was added with 500 µl of concentrated hydrochloric acid and 414.8 mg (3.61 mmol) of indium. After stirring at room temperature for 30 minutes. The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to obtain 87 mg (yield: 75%) of the desired product.

¹ H-NMR (300 MHz) δ; 6.95 (m, 1H), 6.50 (m, 1H), 6.45 (m, 1H), 3.65 (s, -NH ₂ )

Example 2

Preparation of Aniline

95.7 mg (0.78 mmol) of nitrobenzene were dissolved in 3 ml of 25% aqueous tetrahydrofuran solution, and the resulting solution was added with 450 µl of concentrated hydrochloric acid and 357 mg (3.11 mmol) of indium, followed by stirring at room temperature for 30 minutes. The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to obtain 60.4 mg (yield: 84%) of the desired product.

¹ H-NMR (300 MHz) δ; 7.24 (t, 2H), 6.85 (t, 1H), 6.75 (d, 2H), 3.66 (s, -NH ₂ )

Example 3

Preparation of 2- (4-aminophenyl) ethan-1-ol

101 mg (0.60 mmol) of 2- (4-nitrophenyl) ethan-1-ol was dissolved in 25% aqueous tetrahydrofuran solution (3 ml), and the resulting solution was stirred with 350 µl of concentrated hydrochloric acid and 276.4 mg (2.41 mmol) of indium. After the addition, the mixture was stirred at room temperature for 1.5 hours. The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to obtain 81 mg (yield: 98%) of the desired product.

¹ H-NMR (300 MHz) δ; 7.09 (d, 2H), 6.64 (d, 2H), 3.79 (t, 2H), 2.76 (d, 2H)

Example 4

Preparation of 2-Aminophenol

88.0 mg (0.63 mmol) of 2-nitrophenyl was dissolved in 25% aqueous tetrahydrofuran solution (3 ml), and the resulting solution was added with 350 µl of concentrated hydrochloric acid and 291 mg (2.53 mmol) of indium, followed by stirring at room temperature for 1 hour. Stirred. The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to obtain 53 mg (yield: 76%) of the desired product.

¹ H-NMR (300 MHz) δ; 7.98 (m, 1H), 7.82 (d, 2H), 7.53 (t, 1H), 7.34 (t, 1H)

Example 5

Preparation of 4-bromo-3-methylphenylamine

108.0 mg (0.50 mmol) of 1-bromo-2-methyl-4-nitrobenzene was dissolved in 25% aqueous tetrahydrofuran solution (3 ml), and the resulting solution was stirred with 350 µl of concentrated hydrochloric acid and 230.0 mg (2.00 mmol) of indium. After the addition, the mixture was stirred at room temperature for 1 hour. The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to obtain 78 mg (yield: 84%) of the desired product.

¹ H-NMR (300 MHz) δ; 7.27 (d, 1H), 6.58 (s, 1H), 6.41 (d, m, 1H), 3.56 (s, -NH ₂ ), 2.30 (s, 3H)

Example 6

Preparation of 2-amino-5-fluorophenol

70.0 mg (0.44 mmol) of 2-nitro-5-fluorophenol was dissolved in 25% aqueous tetrahydrofuran solution (4 ml), and the resulting solution was added with 250 µl of concentrated hydrochloric acid and 203.0 mg (1.77 mmol) of indium, followed by stirring. Stir at room temperature for 1 hour. The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to obtain 41 mg (yield: 73%) of the desired product.

¹ H-NMR (300 MHz) δ; 6.85 (d, 1H), 7.55 (m, 2H), 4.60 (s, -NH ₂ ), 1.35 (s, -OH)

Example 7

Preparation of hexylamine

94.0 mg (0.72 mmol) of nitrohexane were dissolved in 25% aqueous tetrahydrofuran solution (5 ml), and the resulting solution was added with 450 µl of concentrated hydrochloric acid and 329.0 mg (2.87 mmol) of indium, followed by stirring at room temperature for 0.5 hours. . The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to obtain 65 mg (yield: 90%) of the desired product.

¹ H-NMR (300 MHz) δ; 3.34 (s, -NH ₂ ), 2.68 (t, 2H, J = 6.99 Hz), 1.50 (t, 2H, J = 6.54 Hz), 1.23 (s, 6H), 0.86 (t, 3H, J = 4.92 Hz )

Example 8

Preparation of Cyclopentylamine

109 mg (0.94 mmol) of nitrocyclopentane were dissolved in 25% aqueous tetrahydrofuran solution (5 ml), and 600 µl of concentrated hydrochloric acid and 433.0 mg (3.77 mmol) of indium were added with stirring, followed by stirring at room temperature for 0.5 hours. It was. The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to obtain 63 mg (yield: 78%) of the desired product.

¹ H-NMR (300 MHz) δ; 6.34 (s, -NH ₂ ), 3.51 (m, 1H), 1.89-1.72 (m, 2H), 1.70-1.63 (m, 2H), 1.60-1.40 (m, 4H)

Example 9

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

161 mg (0.69 mmol) of 4- (2-nitro-phenyl) -but-2-enoic acid ethyl ester were dissolved in 5 ml of 25% aqueous tetrahydrofuran solution, and the resulting solution was stirred with 600 µl of concentrated hydrochloric acid and 315 mg of indium. (2.74 mmol) was added, followed by stirring at room temperature for 0.5 hours. The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to obtain 107.9 mg (yield: 77%) 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 Styrylamine

100 mg (0.67 mmol) of (2-nitro-vinyl) -benzene was dissolved in 3 ml of 25% aqueous tetrahydrofuran solution, and the resulting solution was added with 350 µl of concentrated hydrochloric acid and 308 mg (2.68 mmol) of indium, followed by room temperature. Stirred for 1 hour. The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to obtain 75 mg (yield: 94%) of the desired product.

¹ H-300 MHz (CDCl ₃ ) δ; 7.50-6.95 (m, 5H), 3.80 (d, 1H), 3.55 (d, 1H)

Example 11

Preparation of 2-chlorobenzene-1,4-diamine

96.0 mg (0.47 mmol) of 2-chloro-1,4-dinitrobenzene was dissolved in 3 ml of 25% aqueous tetrahydrofuran solution, and the resulting solution was added with 550 µl of concentrated hydrochloric acid and 434.0 mg (3.78 mmol) of indium, followed by stirring. , Was stirred for 2 hours. The pH of the reaction mixture was adjusted to 7-8 with 3N-NaOH, 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, and then purified by neutral alumina to give 63.4 mg (yield: 94%) of the desired product.

¹ H-300 MHz (CDCl ₃ ) δ; 7.00 (d, 1H), 6.07 (m, 2H), 3.72 (s, -NH ₂ )

According to the present invention, the reaction can be carried out in a short time at room temperature by reducing the nitro group with an amine group using an indium metal as well as reducing several nitro groups at once in a short time. It also has the advantage of selectively reducing nitro groups without affecting other functional groups in the molecule, and has the advantage of being an environmentally friendly industrial process because the reaction proceeds easily in aqueous solution.

Claims (9)

A method for reducing a compound having a nitro group to an amine compound, wherein the method uses indium metal. The method of claim 1, wherein the compound having a nitro group has the following formula (1). [Formula 1] In Formula 1, R represents an aliphatic or aromatic compound, n represents an integer of 1-5. The method of claim 1, wherein the compound having a nitro group has a double bond or a triple bond in a molecule. The method according to any one of claims 1 to 3, wherein the amount of indium used is 2-5 equivalents to one nitro group. The method according to claim 4, wherein the reduction reaction is carried out in an aqueous organic solvent phase. The method of claim 5, wherein the organic solvent is tetrahydrofuran, acetonitrile, methanol, ethanol or isopropyl alcohol. 6. The method of claim 5 wherein the acid is further added. 8. The method of claim 7, wherein the acid is HCl or HBr, the amount of which is 1-2 equivalents to indium. A process according to claim 5, wherein the reaction is carried out in the range of 20-25 ° C.