CN103554002B - 1-Phenylindole and preparation method thereof - Google Patents

Abstract

1-Phenylindole of the present invention and preparation method thereof, belongs to organic synthesis field.The present invention is with indoles and bromobenzene for starting raw material, and bromobenzene is from as reaction solvent, and cuprous chloride is catalyzer, and potassium hydroxide is acid binding agent, L-PROLINE is additive synthesis 1-Phenylindole.Instant invention overcomes many deficiencies of prior art, reaction solvent DMSO, DMF etc. in original process are replaced to make solvent with reaction raw materials bromobenzene, copper class catalyzer is recyclable to be reused, productive rate reaches more than 90%, the synthesis cost of 1-Phenylindole can be made generally greatly to reduce, there is good industrial prospect.

Description

1-phenylindole and its preparation method

technical field

The invention relates to 1-phenylindole and a preparation method thereof, belonging to the field of organic synthesis.

Background technique

Indole compounds are an important branch of heterocyclic compounds. Because of their various physiological activities, they are widely used as intermediates of medicines, pesticides, spices, dyes and other fine chemical products. The compound 1-phenylindole of the present invention is not only an important raw material for the preparation of other indole derivatives, but also an important raw material for the synthesis of the pharmaceutical intermediate iminostilbene (iminostilbene itself can not only be used for the prevention and treatment of hepatitis C, but also for the synthesis of important intermediates of antiepileptic drugs carbamazepine, oxcarbazepine and antidepressant imipramine), therefore, the synthesis of 1-phenylindole is very important.

Synthetic reports of 1-phenylindole (1) (MonatshChem, 2011, 142:801-806, SynthCommun, 2012, 42:114-121, ChemCatChem, 2010, 2:1312-1317, ChinChemLett, 2006, 17(3 ): 313-316, CN, 101463010A.2009-06-24. and related citations) Most of them use iodobenzene and indole as starting materials, inorganic bases or organic bases as acid binding agents, copper and copper compounds As a catalyst, DMSO, DMF, ethylene glycol, etc. are used as solvents to react for 24-48 hours to obtain 1-phenylindole. The shortcoming or deficiency of this reaction has: (1) raw material iodobenzene and catalyzer cuprous iodide are expensive and difficult to obtain; (2) there are many by-products in the reaction, and the indole cannot be reacted all the time, which affects the output; (3) The use of solvents such as DMSO, DMF, and ethylene glycol in the reaction is difficult to recycle and reuse, with high cost and heavy pollution; (4) The reaction cycle is long and does not meet the conditions of industrialized large-scale production.

Structural formula 1 1-phenylindole

Contents of the invention

In order to solve the above-mentioned problems, that is, problems such as expensive raw and auxiliary materials, heavy pollution, incomplete reaction of raw materials, and long reaction cycle, the present invention provides a method for synthesizing 1-phenylindole with low cost, low pollution, and short reaction cycle .

The invention uses indole and bromobenzene as starting materials, bromobenzene itself as a reaction solvent, cuprous chloride as a catalyst, potassium hydroxide as an acid-binding agent and L-proline as an additive to synthesize 1-phenylindole. The method provides a method for synthesizing 1-phenylindole with low cost, less pollution and high yield.

The synthetic reaction formula is as follows:

The synthetic method of 1-phenylindole of the present invention, carries out according to the following steps:

(1) Add bromobenzene and indole into a four-neck flask, stir, and heat to reflux at 150-160°C;

(2) Add cuprous chloride, L-proline and potassium hydroxide to react for 8-12 hours, and follow the reaction by TLC; after the indole reaction is completed, cool slightly, filter, wash the brown solid with water, and the insoluble matter is chloride Cuprous, dried, recovered and reused, the organic layer filtrate was washed three times with water, firstly distilled under reduced pressure to recover bromobenzene, and finally distilled under reduced pressure to obtain 1-phenylindole.

In the step (1), bromobenzene is both the reaction raw material and the reaction solvent, and the weight-to-volume ratio of indole to bromobenzene is: 1/(10-30) (g/mL).

Wherein the molar ratio of cuprous chloride to indole in step (2) is 1:4-1:20.

Wherein the molar ratio of L-proline to indole in step (2) is 1:2-1:10.

Wherein the molar ratio of potassium hydroxide to indole in step (2) is: 2:1-10:1.

The present invention overcomes many deficiencies in the prior art, and replaces the reaction solvents DMSO and DMF in the original process with bromobenzene as the reaction raw material, which not only can completely react the raw material indole, but also can be recycled and reused to protect the environment and save costs , the copper catalyst can be recycled and reused, and the yield can reach more than 90%, which can greatly reduce the synthesis cost of 1-phenylindole on the whole, and has a good industrialization prospect.

detailed description

The present invention is described in detail with specific embodiments. The protection scope of the present invention is not limited by the specific embodiments, but by the claims.

Example 1

(1) Add 11.7g (0.1mol) of indole and 117mL of bromobenzene into a four-neck flask, stir, and heat to reflux at 150-160°C. (2) Add 2.47g (0.025mol) of cuprous chloride, 5.75g (0.05mol) of L-proline and 11.22g (0.2mol) of potassium hydroxide to react for 8-12 hours, follow the reaction by TLC, and wait for indole After the reaction, cool slightly, filter, wash the brown solid with water, the insoluble matter is cuprous chloride, dry, recover and reuse, wash the organic layer filtrate with water, recover bromobenzene by distillation under reduced pressure, and finally obtain 1-phenylindole by distillation under reduced pressure Indole 17.76g, yield 92.02%.

Example 2

(1) Add 11.7g (0.1mol) of indole and 351mL of bromobenzene into a four-neck flask, stir, and heat to reflux at 150-160°C. (2) Add 0.49g (0.005mol) of cuprous chloride, 1.15g (0.01mol) of L-proline and 56.11g (1mol) of potassium hydroxide to react for 8-12 hours, follow the reaction by TLC, wait for indole to react Complete, cool slightly, filter, wash the brown solid with water, the insoluble matter is cuprous chloride, dry, recover and reuse, wash the organic layer filtrate with water, recover bromobenzene by distillation under reduced pressure, and finally obtain 1-phenylindole by distillation under reduced pressure 17.17g, yield 88.96%.

Example 3

(1) Add 11.7g (0.1mol) of indole and 175.5mL of bromobenzene into a four-neck flask, stir, and heat to reflux at 150-160°C. (2) Add 0.99g (0.01mol) of cuprous chloride, 2.30g (0.02mol) of L-proline and 28.05g (0.5mol) of potassium hydroxide to react for 8-12 hours, and follow the reaction by TLC. After the reaction, cool slightly, filter, wash the brown solid with water, the insoluble matter is cuprous chloride, dry, recover and reuse, wash the organic layer filtrate with water, recover bromobenzene by distillation under reduced pressure, and finally obtain 1-phenylindole by distillation under reduced pressure Indole 17.19g, yield 89.06%.

Example 4

(1) Add 11.7g (0.1mol) of indole and 234mL of bromobenzene into a four-neck flask, stir, and heat to reflux at 150-160°C. (2) Add 0.66g (0.0066mol) of cuprous chloride, 1.44g (0.012mol) of L-proline and 44.88g (0.8mol) of potassium hydroxide to react for 8-12 hours, follow the reaction by TLC, and wait for indole After the reaction, cool slightly, filter, wash the brown solid with water, the insoluble matter is cuprous chloride, dry, recover and reuse, wash the organic layer filtrate with water, recover bromobenzene by distillation under reduced pressure, and finally obtain 1-phenylindole by distillation under reduced pressure Indole 17.04g, yield 88.29%.

Example 5

(1) Add 11.7g (0.1mol) of indole and 175.5mL of bromobenzene into a four-neck flask, stir, and heat to reflux at 150-160°C. (2) Add 0.49g (0.005mol) of cuprous chloride, 1.15g (0.01mol) of L-proline and 11.22g (0.2mol) of potassium hydroxide to react for 8-12 hours, follow the reaction by TLC, and wait for indole After the reaction, cool slightly, filter, wash the brown solid with water, the insoluble matter is cuprous chloride, dry, recover and reuse, wash the organic layer filtrate with water, recover bromobenzene by distillation under reduced pressure, and finally obtain 1-phenylindole by distillation under reduced pressure Indole 17.37g, yield 90%.

Claims (1)

1. The synthetic method of 1.1-Phenylindole, is characterized in that carrying out according to following step:

   (1) in four-hole boiling flask, add bromobenzene and indoles, stir, be heated to 150-160 DEG C of backflow;

   (2) add the reaction of cuprous chloride, L-PROLINE and potassium hydroxide 8-12 hour, TLC respectively and follow the tracks of reaction; Treat that indole reaction is complete, slightly cold, filtration, brown solid washes with water, and insolubles is cuprous chloride, and dry, recovery is reused, and organic layer filtrate water washs, and bromobenzene is reclaimed in underpressure distillation, and last underpressure distillation obtains 1-Phenylindole;

   Wherein in step (1), the weightmeasurement ratio of indoles and bromobenzene is: 1g/ (10-30) mL;

   In step (2), the mol ratio of cuprous chloride and indoles is 1:4-1:20;

   Wherein in step (2), the mol ratio of L-PROLINE and indoles is 1:2-1:10;

   Wherein in step (2), the mol ratio of potassium hydroxide and indoles is: 2:1-10:1.