CN103848706A - Synthesis method of substituted nitroaniline - Google Patents

Abstract

The invention discloses a synthesis method of substituted o-nitroaniline, which comprises the following steps: under the action of an oxidizing agent, nitrate the substituted aniline and nitrite in a solvent at 20-80°C to obtain substituted nitroaniline, the substituted The structural formula of aniline is: , wherein, R ₁ is p-toluenesulfonyl, acetyl, tert-butoxycarbonyl, benzoyl, -COC(CH ₃ ) ₃ , benzyl or methyl; R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are each independently C1-C4 alkyl, C1-C4 alkoxy, halogen, H, NO ₂ , OCF ₃ or aryloxy, and at least one of R ₂ , R ₄ and R ₆ is H; The nitration reaction means that at least one of R ₂ , R ₄ and/or R ₆ whose value is H on the substituted aniline is replaced by NO ₂ . The synthesis method of the present invention does not require high temperature and high pressure, the conditions are milder, and the operation is safer; no strong acid is used, the aftertreatment is simple, and the environmental pollution and harm are light.

Description

The synthetic method of substituted nitroaniline

technical field

The invention belongs to the field of organic synthesis, and in particular relates to a synthesis method of substituted nitroanilines.

Background technique

Various substituted nitroanilines are important pharmaceutical, agricultural and chemical raw materials, and important intermediates of dyes and pigments. All along with the rapid development of the domestic organic pigment industry, more and more manufacturers have turned their attention to the production of these intermediates. In order to narrow the gap between my country's organic pigment industry and foreign countries, it is imminent to develop a more economical and advanced synthesis process for organic pigment intermediates. The preparation methods of existing nitroaniline mainly contain the following two kinds: 1. It is obtained by ammonolysis of o-chloronitrobenzene. Chloronitrobenzene and ammonia enter the reaction pipeline and stay for 20 minutes. The pressure is reduced to 98kPa once by the pneumatic film regulating valve, and then enter the expansion tank for evaporation and deamination. After adding part of liquid ammonia, continue to be used for ammonolysis, and the deammoniated material can be processed to obtain the product. The existing method needs to be carried out under high temperature and high pressure conditions, and the post-treatment steps are many and cumbersome, resulting in low yield, high cost, and a large amount of difficult-to-treat wastewater; 2. The most classic method is to use concentrated nitrogen-protected aniline The mixed acid of sulfuric acid and concentrated nitric acid is used to digest and then remove the protective agent. This method is widely used in laboratories and industrial production. However, this method uses strong acid and produces a large amount of waste acid, which will pollute the environment and the production process is not safe. .

Contents of the invention

The purpose of the present invention is to overcome the above-mentioned defects in the existing nitroaniline synthesis, and provide a synthetic method of substituted o-nitroaniline with mild reaction conditions and less pollution.

The technical scheme adopted by the present invention to realize the above object is as follows:

A kind of synthetic method of substituted nitroaniline,

Including the following steps:

Under the action of an oxidant, substituted aniline and nitrite are nitrated in a solvent at 20-80°C to obtain substituted nitroaniline,

，其中，R₁为对甲基苯磺酰基、乙酰基、叔丁氧羰基、苯甲酰基、-COC(CH₃)₃、苄基或甲基；R₂、R₃、R₄、R₅和R₆各自独立的为C1-C4烷基、C1-C4烷氧基、卤素、H、NO₂、OCF₃或芳氧基，且R₂、R₄和R₆中至少有一个为H； The structural formula of the substituted aniline is:

, wherein, R ₁ is p-toluenesulfonyl, acetyl, tert-butoxycarbonyl, benzoyl, -COC(CH ₃ ) ₃ , benzyl or methyl; R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are each independently C1-C4 alkyl, C1-C4 alkoxy, halogen, H, NO ₂ , OCF ₃ or aryloxy, and at least one of R ₂ , R ₄ and R ₆ is H;

The nitration reaction means that at least one of R ₂ , R ₄ and/or R ₆ whose value is H on the substituted aniline is replaced by NO ₂ .

Depending on whether R ₂ , R ₄ and/or R ₆ have H, the nitration reaction can be substituted with ortho or para nitro. For example, when R ₂ is H, the structural formula of the substituted nitroaniline obtained by the above nitration reaction is:

，

,

When both R ₂ and R ₄ are H, NO ₂ can replace R ₂ or R ₄ , and the substituted nitroaniline has the following para-substituted structural formula in addition to the above-mentioned ortho-substituted structural formula:

。

.

Further, the aryloxy group is preferably , wherein, R ₇ is C1-C4 alkoxy, C1-C4 alkyl or H.

Preferably, the solvent is an organic solvent such as acetonitrile, dichloromethane, tetrahydrofuran, dioxane, dimethylformamide, nitromethane, toluene or dichloroethane.

Preferably, the nitrite is sodium nitrite, silver nitrite or potassium nitrite.

The substituted aniline is nitrated with excess nitrite, preferably, the molar ratio of the substituted aniline to nitrite is 1: (1-5), most preferably 1:2.

Preferably, the oxidizing agent is ammonium persulfate, ammonium persulfate, potassium persulfate, potassium persulfate or iodobenzene acetate.

Preferably, the molar ratio of the substituted aniline to the oxidizing agent is 1:(0.6-5).

Beneficial effect

(1) The reaction does not require high temperature and high pressure, the conditions are milder, and the operation is safer; (2) No strong acid is required, the post-treatment is simple, and the environmental pollution and harm are light.

Description of drawings

Fig. 1 is the hydrogen spectrum of embodiment 1 gained product a '.

Fig. 2 is the hydrogen spectrum of embodiment 2 gained product b '.

Fig. 3 is the hydrogen spectrum of embodiment 2 gained product b ''.

Fig. 4 is the hydrogen spectrum of embodiment 3 gained product c '.

Fig. 5 is the hydrogen spectrum of embodiment 4 gained product d '.

Fig. 6 is the hydrogen spectrum of embodiment 5 gained product e '.

Fig. 7 is the carbon spectrum of embodiment 5 gained product e '.

Detailed ways

The present invention will be described in further detail below in conjunction with preferred embodiments of the present invention. It should be understood that the preferred embodiments described here are only used to illustrate and explain the present invention, and are not intended to limit the present invention.

Example 1

，Ts为对甲苯磺酰基。

, Ts is p-toluenesulfonyl.

Add compound a (0.3mmol), 0.6mmol NaNO ₂ and 0.2mmol potassium hydrogen persulfate to the reaction vessel, add 3ml of nitromethane, and stir at 50°C for 2 hours; after the detection reaction is completed, remove the nitromethane by rotary evaporation 1. The mixture of ethyl acetate and petroleum ether (volume ratio 1:10) was used as the eluent to pass through a silica gel column to obtain the product a' with a yield (98%).

Example 2

Add compound b (0.3mmol), 0.6mmol of NaNO ₂ and 0.2mmol of potassium hydrogen persulfate to the reaction vessel, add 3ml of nitromethane, and stir at 50°C for 3 hours; Methyl methane was passed through a silica gel column with a mixture of ethyl acetate and petroleum ether (volume ratio 1:8) to obtain products b' (50% yield) and b'' (32% yield).

Example 3

Add compound c (0.3mmol), 0.6mmol of NaNO ₂ and 0.2mmol of potassium hydrogen persulfate to the reaction vessel, add 3ml of nitromethane as a solvent, and stir at 50°C for 3 hours; Nitromethane was removed, and a mixture of ethyl acetate and petroleum ether (volume ratio 1:8) was used as the eluent to pass through a silica gel column to obtain the product c' with a yield of 62%.

Example 4

Add compound d (0.3mmol), 0.6mmol of KNO ₂ and 0.2mmol of potassium hydrogen persulfate to the reaction vessel, add 5ml of nitromethane, and stir at 60°C for 4 hours; after the detection reaction is completed, the solvent is removed by rotary evaporation , using a mixture of ethyl acetate and petroleum ether (volume ratio 1:6) as the eluent to pass through a silica gel column to obtain the product d' with a yield of 32%.

Example 5

Add compound e (0.3mmol), 0.6mmol of AgNO ₂ and 0.2mmol of potassium hydrogen persulfate to the reaction vessel, add 3ml of nitromethane, and stir at 50°C for 3 hours; Methyl methane, using a mixture of ethyl acetate and petroleum ether (volume ratio 1:6) as the eluent, passed through a silica gel column to obtain the product e', with a yield of 43%.

Example 6

Add compound f (0.3mmol), 0.6mmol of NaNO ₂ and 0.2mmol of commercially available Oxone (the amount is based on potassium persulfate) into the reaction vessel, add 3ml of nitromethane, and stir at 50°C for 1.5 hours; detect After the reaction was completed, the nitromethane was removed by rotary evaporation, and the mixture of ethyl acetate and petroleum ether (volume ratio 1:10) was used as the eluent to pass through a silica gel column to obtain the product f' with a yield of 98%.

Example 7

The difference from Example 1 is that compound a (0.3mmol), 0.6mmol NaNO ₂ and 0.9mmol iodobenzene acetate (PhI(OAc) ₂ ) were added to the reaction vessel, 3ml of dichloromethane (DCM) was added, and the 25°C) and stirred for 3 hours; after the completion of the detection reaction, the DCM was removed by rotary evaporation, and the mixture of ethyl acetate and petroleum ether (volume ratio 1:10) was used as the eluent to pass through the silica gel column to obtain the product a', the yield ( 82%).

Example 8

The difference from Example 1 is that the yield of compound a' was 98% after each raw material was added into the reaction vessel and stirred at room temperature (25°C) for 36 hours.

Example 9

Add compound a (0.3mmol), 0.6mmol KNO ₂ and 0.2mmol potassium hydrogen persulfate to the reaction vessel, add 3ml of nitromethane, and stir at 50°C for 2 hours; after the detection reaction is completed, nitromethane is removed by rotary evaporation 1. The mixture of ethyl acetate and petroleum ether (volume ratio 1:10) was used as the eluent to pass through a silica gel column to obtain the product a' with a yield (89%).

Example 10

The difference from Example 1 is that 0.3mmol of compound a , 0.36mol of NaNO ₂ and 0.2mmol of potassium hydrogen persulfate were added to the reaction vessel, and the yield of product a' was 90%.

Example 11

，硝化反应得到：，GC检测化合物g’的产率为58%。 Unlike Example 8, compound a is replaced by compound g,

, the nitrification reaction gives: , GC detected that the yield of compound g' was 58%.

Example 11

，硝化反应得到：

，GC检测化合物h’的产率为41%。 Unlike Example 8, compound a is replaced by compound h,

, the nitrification reaction gives:

, GC detected that the yield of compound h' was 41%.

The above-mentioned substituted aniline raw materials of the present invention can be prepared from commercially available ones, or by using corresponding aniline raw materials through amino protection reaction according to the prior art. The prior art has a detailed description of this kind of amino protection reaction. For specific operations, please refer to: Gao Xuhong, Li Bingqi, Amino Protection and Application in Organic Synthesis (Review), Journal of Shihezi University (Natural Science Edition ), Volume 3, No. 1999 Phase 1 p76-86.

Described each substituted aniline raw material also can adopt following method preparation:

，

,

For example, the preparation process of compound a: add 5mmol p-methylaniline and 1.05eq TsCl into a round bottom flask, stir slowly with a magnet, slowly add 3eq pyridine dropwise into the above reaction flask, and remove pyridine by rotary evaporation after 12 hours of reaction , after adding water, extract with ethyl acetate, wash the extracted organic phase with water for 3-6 times repeatedly, then wash the organic phase with saturated brine, spin the organic phase to remove the solvent to obtain a solid substance, wash with petroleum ether several times (remove residual pyridine ) and then dried to obtain the target product.

Finally, it should be noted that: the above is only a preferred embodiment of the present invention, and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, for those skilled in the art, it still The technical solutions recorded in the foregoing embodiments may be modified, or some technical features thereof may be equivalently replaced. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims (6)

1. a synthetic method for substituted-nitrobenzene amine,

Comprise the steps:

Under oxygenant effect, substituted aniline and nitrite obtain substituted-nitrobenzene amine in 20～80 DEG C of nitration reactions in solvent,

The structural formula of described substituted aniline is:

, wherein, R ₁for to Methyl benzenesulfonyl base, ethanoyl, tertbutyloxycarbonyl, benzoyl ,-COC (CH ₃) ₃, benzyl or methyl; R ₂, R ₃, R ₄, R ₅and R ₆be independently C1-C4 alkyl, C1-C4 alkoxyl group, halogen, H, NO separately ₂, OCF ₃or aryloxy, and R ₂, R ₄and R ₆in have one at least for H;

Nitration reaction refers to the R that on described substituted aniline, at least one value is H ₂, R ₄and/or R ₆by NO ₂institute replaces.

2. the synthetic method of substituted-nitrobenzene amine according to claim 1, is characterized in that, described solvent is acetonitrile, methylene dichloride, tetrahydrofuran (THF), dioxane, dimethyl formamide, Nitromethane 99Min., toluene or ethylene dichloride.

3. the synthetic method of substituted-nitrobenzene amine according to claim 1, is characterized in that, described nitrite is Sodium Nitrite, silver nitrite or potassium nitrite.

4. according to the synthetic method of substituted-nitrobenzene amine described in claim 1 or 3, it is characterized in that, the mol ratio of described substituted aniline and nitrite is 1:(1～5).

5. the synthetic method of substituted-nitrobenzene amine according to claim 1, is characterized in that, described oxygenant is hydrogen persulfate amine, ammonium persulphate, potassium hydrogen persulfate, Potassium Persulphate or acetic acid iodobenzene.

6. according to the synthetic method of substituted-nitrobenzene amine described in claim 1 or 5, it is characterized in that, the mol ratio of described substituted aniline and oxygenant is 1:(0.6～5).

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