A kind of preparation method of 4-chloroindole-3-acetic acid

Abstract

The invention discloses a 4-chloroindole-3-acetic acid preparing method. The method specifically comprises the steps of 1, conducting condensation reaction of a compound i and DMFDMA at the temperature of 80-120 DEG C in anhydrous DMF solvent, so that a compound ii is generated; 2, dissolving the compound ii in solvent formed by mixing THF with alcohol, adding Raney nickel and adding hydrazine hydrate dropwise for reaction at the temperature of 15-30 DEG C in an inert atmosphere, and obtaining a compound iii after reaction ends completely; 3, dissolving the compound iii in solvent, adding inorganic strong base and a phase transfer catalyst, adding a compound iv dropwise at the temperature of 20-35 DEG C for substitution reaction, conducting heating for backflow after the compound iv is added, and obtaining a compound v after reaction ends completely; 4, hydrolyzing the compound v to obtain the target product 4-chloroindole-3-acetic acid. According to the preparing method, no highly-toxic product is adopted as raw materials, and the whole reaction process is safe.

Description

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a preparation method of 4-chloroindole-3-acetic acid. Background technique

[0002] 4-chloroindole-3-acetic acid (4-CIAA), is a kind of IAA (indole acetic acid) plant growth hormone, which can not only promote growth, but also inhibit growth; both can accelerate germination, and can also inhibit germination; It can prevent flowers and fruits from falling, and it can also thin flowers and fruits, which has duality.

[0003] The synthetic method of existing 4-chloroindole-3-acetic acid has the following several kinds:

[0004] Masato et al. (Biosci.Biotechnol.Biochem.,64(4),808-815,2000) synthesized 4-chloroindole-3-acetic acid and its related ester compounds, the method has a long route, the total yield of the three-step reaction is 58.9%, the product purity is low, and a highly toxic cyanide is used simultaneously, which is not conducive to the industrial production of the prod...

Examples

Embodiment 1

[0038] A preparation method of 4-chloroindole-3-acetic acid, the steps are as follows:

[0039] 1) Synthesis of N,N-dimethyl-2-chloro-6-nitrostyrylamine: 200g of 2-chloro-6-nitrotoluene and 183g of DMFDMA were added to 150ml of anhydrous DMF solution, heated To 80 ~ 120 ℃, heat preservation reaction for 4 hours, use GC detector to detect the reaction end point, after the reaction is complete, cool the obtained product to room temperature, and add 1L toluene solution to the reaction system to dissolve the product, after dissolution, use saturated salt Wash with water, then dry over anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain 290 g of crude N,N-dimethyl-2-chloro-6-nitrostyrylamine;

[0040] 2) Synthesis of 4-chloroindole: 290g of crude N,N-dimethyl-2-chloro-6-nitrostyrylamine was dissolved in a mixed solvent of 250mlTHF and 250ml methanol, and after dissolution, the , At 30°C, add 40g of Raney nickel, and dropwise add 300ml of hydrazine hy...

Embodiment 2

[0061] A preparation method of 4-chloroindole-3-acetic acid, the steps are as follows:

[0062] 1) Synthesis of N,N-dimethyl-2-chloro-6-nitrostyrylamine: same as Example 1.

[0063] 2) Synthesis of ethyl 4-chloroindole-3-acetate: 290 g of N,N-dimethyl-2-chloro-6-nitrostyrylamine crude product prepared in step 1) was dissolved in 500 ml of methanol solvent After dissolving, add 40g of Raney nickel and dropwise add 300ml of hydrazine hydrate with a concentration of 80% under nitrogen protection at 15°C to make N,N-dimethyl-2-chloro-6-nitro -NO in styrylamine 2 Reduction to -NH 2 , The C-N bond in -C=C-N- in N,N-dimethyl-2-chloro-6-nitrostyrylamine is broken, and the ring closure reaction is carried out in the reaction system, the obtained product is filtered, the filtrate is concentrated, Distillation under reduced pressure gave 112 g of pure 4-chloroindole, and the combined steps 1) and 2) were used to calculate the yield. The molar yield of 4-chloroindole was 63.5%, and its...

Embodiment 3

[0067] A preparation method of 4-chloroindole-3-acetic acid, the steps are as follows:

[0068] 1) Synthesis of N,N-dimethyl-2-chloro-6-nitrostyrylamine: same as Example 1.

[0069] 2) Synthesis of 4-chloroindole-3-ethyl acetate: same as Example 1.

[0070] 3) Synthesis of 4-chloroindole-3-ethyl acetate: same as Example 1.

[0071] 4) Synthesis of 4-chloroindole-3-acetic acid: the 4-chloroindole-3-ethyl acetate crude product of 130g is dissolved in the mixed solvent of 500ml water and 500ml methyl alcohol, adds the sodium hydroxide of 120g, is heated to Reflux at 60-70°C for 3 hours. Then the reaction solution was concentrated to dryness under reduced pressure, the residue was dissolved in 500ml of water, 500ml of dichloromethane was added for washing and layering, the pH of the aqueous phase was adjusted to 1-2 with concentrated hydrochloric acid, and then extracted with ethyl acetate, Merge with the organic phase, then dry over anhydrous sodium sulfate, concentrate to obt...

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a preparation method of 4-chloroindole-3-acetic acid. Background technique

[0002] 4-chloroindole-3-acetic acid (4-CIAA), is a kind of IAA (indole acetic acid) plant growth hormone, which can not only promote growth, but also inhibit growth; both can accelerate germination, and can also inhibit germination; It can prevent flowers and fruits from falling, and it can also thin flowers and fruits, which has duality.

[0003] The synthetic method of existing 4-chloroindole-3-acetic acid has the following several kinds:

[0004] Masato et al. (Biosci.Biotechnol.Biochem.,64(4),808-815,2000) synthesized 4-chloroindole-3-acetic acid and its related ester compounds, the method has a long route, the total yield of the three-step reaction is 58.9%, the product purity is low, and a highly toxic cyanide is used simultaneously, which is not conducive to the industrial production of the prod...

Examples

Embodiment 1

[0038] A preparation method of 4-chloroindole-3-acetic acid, the steps are as follows:

[0039] 1) Synthesis of N,N-dimethyl-2-chloro-6-nitrostyrylamine: 200g of 2-chloro-6-nitrotoluene and 183g of DMFDMA were added to 150ml of anhydrous DMF solution, heated To 80 ~ 120 ℃, heat preservation reaction for 4 hours, use GC detector to detect the reaction end point, after the reaction is complete, cool the obtained product to room temperature, and add 1L toluene solution to the reaction system to dissolve the product, after dissolution, use saturated salt Wash with water, then dry over anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain 290 g of crude N,N-dimethyl-2-chloro-6-nitrostyrylamine;

[0040] 2) Synthesis of 4-chloroindole: 290g of crude N,N-dimethyl-2-chloro-6-nitrostyrylamine was dissolved in a mixed solvent of 250mlTHF and 250ml methanol, and after dissolution, the , At 30°C, add 40g of Raney nickel, and dropwise add 300ml of hydrazine hy...

Embodiment 2

[0061] A preparation method of 4-chloroindole-3-acetic acid, the steps are as follows:

[0062] 1) Synthesis of N,N-dimethyl-2-chloro-6-nitrostyrylamine: same as Example 1.

[0063] 2) Synthesis of ethyl 4-chloroindole-3-acetate: 290 g of N,N-dimethyl-2-chloro-6-nitrostyrylamine crude product prepared in step 1) was dissolved in 500 ml of methanol solvent After dissolving, add 40g of Raney nickel and dropwise add 300ml of hydrazine hydrate with a concentration of 80% under nitrogen protection at 15°C to make N,N-dimethyl-2-chloro-6-nitro -NO in styrylamine 2 Reduction to -NH 2 , The C-N bond in -C=C-N- in N,N-dimethyl-2-chloro-6-nitrostyrylamine is broken, and the ring closure reaction is carried out in the reaction system, the obtained product is filtered, the filtrate is concentrated, Distillation under reduced pressure gave 112 g of pure 4-chloroindole, and the combined steps 1) and 2) were used to calculate the yield. The molar yield of 4-chloroindole was 63.5%, and its...

Embodiment 3

[0067] A preparation method of 4-chloroindole-3-acetic acid, the steps are as follows:

[0068] 1) Synthesis of N,N-dimethyl-2-chloro-6-nitrostyrylamine: same as Example 1.

[0069] 2) Synthesis of 4-chloroindole-3-ethyl acetate: same as Example 1.

[0070] 3) Synthesis of 4-chloroindole-3-ethyl acetate: same as Example 1.

[0071] 4) Synthesis of 4-chloroindole-3-acetic acid: the 4-chloroindole-3-ethyl acetate crude product of 130g is dissolved in the mixed solvent of 500ml water and 500ml methyl alcohol, adds the sodium hydroxide of 120g, is heated to Reflux at 60-70°C for 3 hours. Then the reaction solution was concentrated to dryness under reduced pressure, the residue was dissolved in 500ml of water, 500ml of dichloromethane was added for washing and layering, the pH of the aqueous phase was adjusted to 1-2 with concentrated hydrochloric acid, and then extracted with ethyl acetate, Merge with the organic phase, then dry over anhydrous sodium sulfate, concentrate to obt...

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