CN102924330A - Method for large-scale preparation of 5-amino-1-naphthyl nitrile - Google Patents

Abstract

The invention relates to a method for large-scale preparation of 5-amino-1-naphthyl nitrile. The method mainly comprises the steps of: by adopting nitronaphthalene as a starting material, carrying out bromination reaction on nitronaphthalene, so as to obtain 5-bromine-1-nitronaphthalene; reacting 5-bromine-1-nitronaphthalene with cuprous cyanide to obtain 5-nitro-1-naphthyl nitrile; and finally reducing 5-nitro-1-naphthyl nitrile to obtain the target product 5-amino-1-naphthyl nitrile. The method has the advantages that: (1) the starting raw material (nitronaphthalene) is cheap; (2) the reaction condition is relatively mild; and (3) the operation is simple and safe (no column chromatography isolation is carried out, and hazardous reagents is avoided using), so that the method is the method easy for large-scale commercial preparation of 5-amino-1-naphthyl nitrile.

Description

A kind of method of large-scale preparation 5-amino-1-naphthalene nitrile

technical field

The invention relates to a method for large-scale preparation of naphthalene ring compounds, in particular to a method for large-scale preparation of 5-amino-1-naphthalene nitrile.

Background technique

5-Amino-1-naphthonitrile is a dye and an intermediate (it can be used to prepare nitric oxide fluorescent probes and a series of other compounds).

There are mainly two kinds of existing methods for preparing 5-amino-1-naphthalene nitrile, one of which is: taking naphthoic acid as starting material, and obtaining target (Schuster, I.I.Magn.Reson.Chem.1996,34 through three-step reaction) , 301-310; Repine, J.T., Johnson, D.S., White, A.D., Favor, D.A., Stier, M.A., Yip, J., Rankin, T., Ding, Q., Maiti, S.N., Tetrahedron Lett., 2007, 48 , 5539-5541), the synthetic route is as follows:

The defect of this method is that the price of used naphthoic acid (starting material) is relatively expensive, needs to use the stronger reagent (sodium azide) of danger, and yield is lower (the reaction yield of first two steps is respectively 62% and 58%, the third step yield has no report), and product separation difficulties etc.; the second is: take naphthalene nitrile as starting raw material, obtain target (Peng, X., Fukui, N., Mizuta, M., Suzuki, H., Org.Biomol.Chem.2003, 1, 2326-2335), the synthesis strategy is as follows:

The deficiency of this method is: the price of used starting material (naphthalene nitrile) is very expensive, intermediate product has (isomer) isomer (requiring column chromatography to separate), yield is lower (two-step reaction is respectively 40% and 90%).

In summary, there are problems such as higher preparation cost of 5-amino-1-naphthalene nitrile (target object), harsh reaction conditions, and low yield of the target object in the prior art, resulting in 5-amino-1-naphthalene nitrile Difficult for large-scale commercial preparation.

Contents of the invention

The object of the present invention is to provide a method for easy large-scale commercial preparation of 5-amino-1-naphthonitrile, which overcomes the problems in the prior art.

The method for preparing 5-amino-1-naphthalene nitrile of the present invention, comprises the steps:

(1) the step of preparing 1-bromo-5-nitronaphthalene by nitronaphthalene,

(2) the step of preparing 5-nitro-1-naphthalene nitrile by 1-bromo-5-nitronaphthalene, and

(3) A step of producing 5-amino-1-naphthonitrile (target substance) from 5-nitro-1-naphthonitrile.

The present invention has the advantages of: 1. the price of the starting material (nitronaphthalene) used is low; Process for the commercial preparation of 5-amino-1-naphthonitrile.

Detailed ways

In a preferred technical solution of the present invention, nitronaphthalene can be brominated with liquid bromine to obtain 1-bromo-5-nitronaphthalene, and the temperature of the bromination reaction is 80°C to 85°C.

In another preferred technical solution of the present invention, in the presence of a base (such as (but not limited to): Na ₂ CO ₃ or K ₂ CO _{3 ,} etc.), 1-bromo-5-nitronaphthalene is prepared at 100 ℃～152℃, react with cuprous cyanide (CuCN) in an aprotic polar organic solvent (preferably N,N-dimethylformamide) to obtain 5-nitro-1-naphthalenenitrile.

In the present invention, various methods can be adopted for preparing 5-amino-1-naphthalene nitrile (target object) by 5-nitro-1-naphthalene nitrile, such as "catalytic hydrogenation reduction method" or using other reducing reagents (such as (but Not limited to): zinc, iron, tin, stannous chloride, ferrous sulfate, sodium dithionite, sulfur, sodium hydrosulfide, sodium sulfide, ammonium oxalate or oxalic acid, etc.) reduction. In yet another preferred technical solution of the present invention, the "catalytic hydrogenation reduction method" is used to reduce 5-nitro-1-naphthalenenitrile to obtain the target (5-amino-1-naphthalenenitrile);

In the "catalytic hydrogenation reduction method", the present invention recommends the use of a palladium/carbon catalyst, preferably a palladium/carbon catalyst with a palladium content of 5wt% or 10wt% (the total weight of the palladium/carbon catalyst is 100wt%); The hydrogen pressure is preferably 0.4MPa.

The present invention will be further described below in conjunction with embodiment, and its purpose is only to understand content of the present invention better. It should be understood that the examples given do not limit the protection scope of the present invention:

Example 1

(1) Preparation of 1-bromo-5-nitronaphthalene:

Heat 500g of nitronaphthalene (2.89mol) to 80-85°C to melt into a deep red liquid, keep the temperature constant and slowly add 450g of liquid bromine (2.81mol) dropwise within 2-3 hours. A large amount of acid gas released by the reaction is collected with lye. After one hour of reaction, the heating was stopped, and the reaction solution was poured into about 3 liters of ice water, and a large amount of yellow precipitate was precipitated, which was vacuum filtered to obtain a yellow solid, which was recrystallized with ethanol. 343 g of yellow needle crystals were obtained. Yield: 47%.

(2) Preparation of 5-nitro-1-naphthalene nitrile:

Dissolve 343g (1.36mol) of 1-bromo-5-nitronaphthalene, 125g (1.4mol) of cuprous cyanide, and 193g (1.4mol) of potassium carbonate in 1500ml of N,N-dimethylformamide (DMF) , heated for 12 hours, the reaction solution was poured into a large amount of ice water (5 liters), and a large amount of needle-shaped crystals were precipitated. The solid was collected by vacuum filtration, washed with water repeatedly (500 ml for 3 times), and 237 g of a yellow solid was obtained. Yield: 88%.

(3) Preparation of 5-amino-1-naphthalene nitrile (target object):

Dissolve 50 g (2 mol) of 5-nitro-1-naphthalene nitrile in 1000 ml of methanol, carefully add 1 g of palladium/carbon catalyst (containing 10% palladium) under the protection of argon, pass hydrogen (0.4 MPa), under vigorous stirring After 3 hours of reaction at room temperature. The palladium/carbon catalyst was filtered off, and 40.3 g of a colorless solid was spin-dried. Yield: 95%.

Claims (8)

1. A method for preparing 5-amino-1-naphthalene nitrile, comprising the steps of: (1) the step of preparing 1-bromo-5-nitronaphthalene by nitronaphthalene, (2) the step of preparing 5-nitro-1-naphthalene nitrile by 1-bromo-5-nitronaphthalene, and (3) The step of preparing the target substance from 5-nitro-1-naphthonitrile. 2. the method for claim 1 is characterized in that, in described step (1), nitronaphthalene undergoes liquid bromination bromination reaction, obtains 1-bromo-5-nitronaphthalene, and described liquid bromine The temperature of the bromination reaction is 80°C to 85°C. 3. The method according to claim 1, characterized in that, in the step (2), under the condition that there is a base, the 1-bromo-5-nitronaphthalene is heated at 100° C. to 152° C. React with cuprous cyanide in an aprotic polar organic solvent to obtain 5-nitro-1-naphthalene nitrile. 4. The method according to claim 3, wherein said alkali is sodium carbonate or salt of wormwood. 5. The method according to claim 3, wherein said aprotic polar organic solvent is N,N-dimethylformamide. 6. The method according to claim 1, characterized in that, in the step (3), the "catalytic hydrogenation reduction method" is used to reduce 5-nitro-1-naphthalene nitrile to obtain the target object. 7. the method for claim 6 is characterized in that, in described " catalytic hydrogenation reduction method ", catalyzer is palladium/carbon catalyst, is 100wt% with the gross weight of palladium/carbon catalyst, and palladium content is 5wt% or 10wt%. 8. The method according to claim 6, wherein the hydrogen pressure is 0.4MPa.