CN102516122A - Environment friendly method for preparing DMF (Dimethyl Formamide) solution of 2-hydroxy-benzonitril, DMF solution of 2-hydroxy-benzonitril and application thereof - Google Patents

Abstract

The invention discloses an environment friendly method for preparing a DMF (Dimethyl Formamide) solution of 2-hydroxy-benzonitril, which is characterized in that triphosgene and salicylamide are respectively added into DMF to be fully reacted. With the preparation method disclosed by the invention, more than 98% of 2-hydroxy-benzonitril (excluding solvent) can be obtained, the chemical conversion and the selectivity are both greater than 98%, and no problems exist if the 2-hydroxy-benzonitril is directly applied for the next step of reaction. In the process of production, no polluting waste gas and waste water are discharged, scraps are inorganic salts which can directly used or organic amine hydrochlorides which can be recycled, the comprehensive production cost of the 2-hydroxy-benzonitril is greatly reduced, and the production process is environment friendly.

Description

Environmentally friendly method for preparing DMF solution of o-hydroxybenzonitrile, DMF solution of o-hydroxybenzonitrile and application thereof

technical field

The discovery relates to an environmentally friendly method for preparing a DMF solution of o-hydroxybenzonitrile, a DMF solution of o-hydroxybenzonitrile and applications thereof. the

Background technique

O-hydroxybenzonitrile, commonly known as salicylonitrile, also known as 2-hydroxybenzonitrile, o-hydroxybenzonitrile, 2-cyanophenol, etc., molecular formula C7H5NO, CAS registration number 611-20-1, has certain water solubility, Pka =7.17, unstable to strong bases and oxidants. As a pharmaceutical intermediate, it can be used to synthesize Bunirolol hydrochloride, a drug for treating hypertension and angina pectoris. As a pesticide intermediate, it can be used to synthesize the fungicide azoxystrobin. In addition, it can also synthesize a variety of spices and liquid crystal materials. the

Salicylamide, white or slightly pink crystalline powder. The melting point is 140°C. Salicylamide is easily soluble in hot water, alcohol, ether and chloroform, slightly soluble in cold water. The pH of a saturated aqueous solution at 28°C is about 5. Salicylamide has a slightly bitter taste. Antipyretic and analgesic drugs are also used to prepare drugs such as o-ethoxybenzamide (ie Zhitongling). the

There are many research materials on the preparation of o-hydroxybenzonitrile, but there are not many with large-scale production value, mainly including: (1) salicylaldehyde and hydroxylamine to obtain oxime, and then dehydrate to obtain the product, US5637750, CN201010106946; (2) salicylaldehyde The product is obtained by one-step dehydration of the amide, and the high-temperature dehydration is catalyzed by a fixed bed, and the yield is 87%, which is suitable for continuous large-scale production of more than 1,000 tons, US6248917; (3) dehydration of ammonium salicylate (or a mixture of salicylic acid and ammonia) to obtain Products, US7629486, CN201110058467. The advantages and disadvantages of various methods CN201110058467 are introduced in more detail, and what needs to be added here is: (1) from the perspective of production cost, only salicylamide or ammonium salicylate dehydration to prepare o-hydroxybenzonitrile has obvious advantages; (2) From the perspective of market demand, the current annual demand is expected to be around 1,000 tons. Continuous production equipment requires a large investment, and technical stability requires long-term reliability test verification to truly realize large-scale production. Therefore, the dehydration method of salicylamide to prepare o-hydroxybenzonitrile is a method suitable for large-scale production. the

The use of amide dehydration method to prepare nitrile compounds is a basic method in organic synthesis, see the chapter "Amides to Nitriles" in "Comprehensive Organic Transformations", author Richard C. Larock. The common methods are: (1) direct dehydration method of strong dehydrating agents such as thionyl chloride, phosphorus oxychloride, phosphorus pentachloride, phosgene, phosphorus pentoxide, acid anhydride and acid chloride; (2) HMPA assisted dehydration, Canadian Journal of Chemistry, 1971, 49, 2897; (3) Lewis acid titanium tetrachloride/triethylamine, aluminum trichloride/potassium iodide and other unconventional reagents. Among them, the first type has industrial prospects. Considering that there is an ortho hydroxyl group in the molecule, it is easy to obtain other by-products instead of o-hydroxybenzonitrile by using phosphorus pentoxide, acid anhydride and acid chloride. Thionyl chloride, phosphorus oxychloride, phosphorus pentachloride and phosgene are difficult to meet the requirements of modern environment-friendly and safe chemical production processes in actual production due to their toxicity, extreme fear of moisture and other reasons. the

Huang Shan et al. reported the technology of preparing salicylonitrile by dehydration of triphosgene and salicylamide (Shanxi Chemical Industry, 2009, 29, 4). Salicylamide and triphosgene were reacted in toluene at 100-105°C, and the crude product was recrystallized with toluene. Although the small test gives a yield of about 90%, the yield is not high in the actual industrial production process, the product quality is difficult to improve, it is difficult to exceed 95%, and there are many impurities, which affect the production of subsequent products and lead to the failure of azoxystrobin. Synthesis is difficult to obtain high-quality products. Although the crude product o-hydroxybenzonitrile can reach a content of more than 98% after multiple purifications, the production cost has risen sharply, which has no practical significance. the

Contents of the invention

The purpose of the present invention is in order to overcome the deficiencies in the prior art, and a kind of method for the DMF solution of the preparation o-hydroxybenzonitrile of environmental friendliness is provided. the

To achieve the above object, the present invention is realized through the following technical solutions:

An environment-friendly method for preparing a DMF solution of o-hydroxybenzonitrile is characterized in that triphosgene and salicylamide are respectively added to DMF for full reaction. the

Preferably, the molar ratio of salicylamide to triphosgene is 1:0.33-1.0. the

Preferably, the molar ratio of salicylamide to triphosgene is 1:0.34-0.5. the

Considering that it is impossible to strictly remove water under the reaction conditions, and there is a small amount of water in the industrial-grade solvents and raw materials generally used, it is necessary to increase the amount of triphosgene appropriately, but excessive use of triphosgene does not affect the recovery of o-hydroxybenzonitrile. Generally speaking, the amount of triphosgene is 0.34-0.5 of the amount of salicylamide, which is more economical. the

Preferably, the reaction temperature is -20-50°C. the

Preferably, the reaction temperature is 5°C to 15°C. the

If the temperature is too low, the energy consumption is high, and the by-products are more when the temperature exceeds 50°C, which affects the product quality. Therefore, in the actual preparation, as long as the temperature is not lower than 5°C and not higher than 15°C; the reaction temperature does not need to be intervened. If it exceeds this temperature range, it needs to be cooled or heated. the

Preferably, triphosgene is added to DMF first, and then salicylamide is added. the

Preferably, the triphosgene is firstly dissolved in an inert solvent, and then added into DMF. the

Preferably, salicylamide is firstly added in DMF, and then triphosgene is added. the

Preferably, triphosgene is dissolved in an inert solvent and then added to the DMF dissolved in salicylamide. the

Preferably, it is characterized in that the inert solvent is selected from hydrocarbons, ethers, ketones or ester inert solvents. the

Preferably, the hydrocarbon inert solvent is selected from alkanes, aromatic hydrocarbons or substituted derivatives thereof. the

Preferably, the ether inert solvent is selected from aliphatic ethers, aromatic ethers or substituted derivatives thereof. the

Preferably, the ketone inert solvent is selected from lower aliphatic ketones or substituted derivatives thereof. the

Preferably, the ester inert solvent is selected from fatty acid esters, aromatic acid esters or substituted derivatives thereof. the

Preferably, after the reaction is completed, add alkali to neutralize and filter to obtain a DMF solution of o-hydroxybenzonitrile. the

Preferably, the base includes one or a mixture of inorganic bases and organic bases. the

Preferably, the inorganic base includes one or more of oxides, hydroxides, carbonates and bicarbonates of alkali metals or alkaline earth metals. Such as ammonia, lithium hydroxide, lithium carbonate, sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, potassium carbonate, potassium bicarbonate, magnesium oxide, magnesium hydroxide, magnesium carbonate, calcium oxide, calcium hydroxide, Calcium carbonate, calcium bicarbonate, etc. or a mixture thereof. the

Preferably, the organic base includes one or more of triethylamine, diethylamine and aniline. Such as triethylamine, tributylamine, diethylisopropylamine, urotropine, triethylenediamine, aniline, N-methylaniline, N,N-dimethylaniline, etc. or their mixtures. the

The present invention adopts two methods. The first method is to add triphosgene to DMF to form Vilsmeier reagent, and then add salicylamide to be dehydrated by Vilsmeier reagent to form o-hydroxybenzonitrile. The second method is to add triphosgene to the DMF solution of salicylamide, and Vilsmeier reagent can get the same result as the catalyst of the reaction process. the

The minimum amount of DMF used is 6 times the amount of triphosgene, preferably, the minimum amount of DMF is 6-20 times the amount of triphosgene. Its purpose is to control the concentration of o-hydroxybenzonitrile in DMF in the range of 5%-40%. This is because considering the needs of actual production and application, too thin will reduce production efficiency, and too thick will make product separation and next reaction stirring difficult. It is better to control the concentration range between 15% and 25%. At this time, the DMF is greatly in excess of the theoretical amount, and there is no need to consider the influence of DMF absorbing hydrogen chloride in the reaction process. the

Second object of the present invention is to provide a kind of DMF solution of o-hydroxybenzonitrile, it is characterized in that, adopt aforementioned method to produce. the

The third object of the present invention is to provide a kind of o-hydroxybenzonitrile, it is characterized in that, adopt the DMF solution of the o-hydroxybenzonitrile produced by aforementioned method, separate and obtain o-hydroxybenzonitrile. the

The fourth object of the present invention is to provide the application of a DMF solution of o-hydroxybenzonitrile in the synthesis of azoxystrobin and bunilol. The DMF solution of o-hydroxybenzonitrile in the present invention can be directly applied to the synthesis of azoxystrobin and bunylol hydrochloride. It can also be used in the synthesis of azoxystrobin and Bunirolol hydrochloride after neutralization with alkali. the

The preparation method in the present invention can obtain o-hydroxybenzonitrile (deducting the solvent) with a content greater than 98%, the chemical conversion rate and selectivity are greater than 99%, and there is no problem in directly applying to the next step reaction. In the production process, there is no polluting waste gas and waste water discharge, and the residue is inorganic salt that can be directly used or organic amine hydrochloride that can be recycled, which greatly reduces the comprehensive production cost of o-hydroxybenzonitrile, and is an environmentally friendly production craft. the

Detailed ways

The present invention will be further described below in conjunction with embodiment. the

Example 1

Under the cooling of the ice-water mixture, 11.88 g (0.04 mol) of triphosgene was added in batches to 50 ml of DMF. Stirring was continued for 30 minutes after the addition was complete. Control the temperature not to exceed 15°C. 13.7 grams of salicylamide (0.1mol) was added to the above reaction solution in batches, and the temperature was controlled at 5-15°C. After the addition was complete, the ice-water cooling bath was removed, the temperature was naturally raised to room temperature, and stirring was continued for one hour to obtain a DMF solution of o-hydroxybenzonitrile. The o-hydroxybenzonitrile content is 98.3%. The chemical conversion rate is 99.1%; the selectivity is 98.2%. the

Example 2

Under the cooling of the ice-water mixture, 11.88 g (0.04 mol) of triphosgene was added in batches to 50 ml of DMF. Stirring was continued for 30 minutes after the addition was complete. Control the temperature not to exceed 15°C. 13.7 g of salicylamide (0.1 mol) was added in batches to the above reaction solution, and the temperature was controlled at 5-15°C. After the addition was complete, the ice-water cooling bath was removed, the temperature was naturally raised to room temperature, and the stirring was continued for one hour; the ice-water mixture was cooled to 15°C again. Add 16.56 g (0.12 mol) of potassium carbonate, stir for 15 minutes, remove the ice-water bath, naturally warm up to room temperature and continue stirring for 6 hours, and filter to obtain a DMF solution of o-hydroxybenzonitrile. The o-hydroxybenzonitrile content is 98.6%. The chemical conversion rate is 99.4%; the selectivity is 98.4%. the

Example 3

Under the cooling of the ice-water mixture, 11.88 g (0.04 mol) of triphosgene dissolved in 25 ml of ethyl acetate was added dropwise to 50 ml of DMF, and stirring was continued for 30 minutes after the addition was complete. Control the temperature not to exceed 15°C. 13.7 g of salicylamide (0.1 mol) was added in batches to the above reaction solution, and the temperature was controlled at 5-15°C. After the feeding was completed, the ice-water cooling bath was removed, the temperature was naturally raised to room temperature, and the stirring was continued for one hour. The ethyl acetate was distilled off by concentration with a rotary evaporator under reduced pressure to obtain a DMF solution of o-hydroxybenzonitrile. The o-hydroxybenzonitrile content is 98.7%. The chemical conversion rate is 99.5%; the selectivity is 98.5%. the

Example 4

Under ice-water mixture cooling, 11.88 g (0.04 mol) of triphosgene dissolved in 25 ml of ethyl acetate was added dropwise to 40 ml of DMF, and stirring was continued for 30 minutes after the addition was complete. Control the temperature not to exceed 15°C. 13.7 g of salicylamide (0.1 mol) was dissolved in 10 ml of DMF and added dropwise to the above reaction solution, controlling the temperature at 5-15°C. Remove the ice-water cooling bath after the feeding is completed, naturally warm up to room temperature, and continue to stir for one hour; re-cool to 15°C with ice-water mixture, add 16.56 grams of potassium carbonate (0.12mol), stir for 15 minutes, remove the ice-water bath, and naturally heat up to Continue to stir at room temperature for 6 hours, filter, concentrate under reduced pressure on a rotary evaporator to remove ethyl acetate to obtain a DMF solution of o-hydroxybenzonitrile. The o-hydroxybenzonitrile content is 98.5%. The chemical conversion rate is 99.2%; the selectivity is 98.3%. the

Example 5

Under the cooling of ice-water mixture, 13.7 g of salicylamide (0.1 mol) was first added into 50 ml of DMF. Then 11.88 g (0.04 mol) of triphosgene was added in batches, and stirring was continued for 30 minutes after the addition was completed. Control temperature 5-15 ℃. After the addition was complete, the ice-water cooling bath was removed, the temperature was naturally raised to room temperature, and stirring was continued for one hour to obtain a DMF solution of o-hydroxybenzonitrile. The o-hydroxybenzonitrile content is 98.2%. The chemical conversion rate is 99.1%; the selectivity is 98.3%. the

Example 6

Under the cooling of the ice-water mixture, 13.7 g of salicylamide (0.1 mol) was first added to 50 ml of DMF, and then 11.88 g (0.04 mol) of triphosgene was added in batches. Control temperature 5-15 ℃. Remove the ice-water cooling bath after the feeding is completed, naturally warm up to room temperature, and continue to stir for one hour; re-cool to 15°C with ice-water mixture, add 16.56 grams of potassium carbonate (0.12mol), stir for 15 minutes, remove the ice-water bath, and naturally heat up to Stirring was continued at room temperature for 6 hours, and a DMF solution of o-hydroxybenzonitrile was obtained by filtration. The o-hydroxybenzonitrile content is 98.3%. The chemical conversion rate is 99.2%; the selectivity is 98.4%. the

Example 7

Under the cooling of ice-water mixture, first add 13.7 grams of salicylamide (0.1mol) in 50 milliliters of DMF, then dissolve 11.88 grams (0.04mol) of triphosgene in 25 milliliters of ethyl acetate, and add dropwise to the DMF of salicylamide In the solution, continue to stir for 30 minutes after the addition, and control the temperature at 5-15°C. Remove the ice-water cooling bath after the feeding is completed, naturally warm up to room temperature, and continue to stir for one hour; re-cool to 15°C with ice-water mixture, add 16.56 grams of potassium carbonate (0.12mol), stir for 15 minutes, remove the ice-water bath, and naturally heat up to Stirring was continued at room temperature for 6 hours, and ethyl acetate was concentrated by filtration to obtain a DMF solution of o-hydroxybenzonitrile. The o-hydroxybenzonitrile content is 98.5%. The chemical conversion rate is 99.4%; the selectivity is 98.3%. the

Application Example 1

In the DMF solution of o-hydroxybenzonitrile obtained in Example 1, add 32 grams (0.095mol, content 95%, provided by Shanghai Heben Pharmaceutical Co., Ltd.) (E)-2-[2-(6-chloro Pyrimidin-4-yloxy)phenyl]-3-methoxymethyl acrylate, 24.84 grams (0.18mol) of anhydrous potassium carbonate, heated to 50°C, stirred for one hour; then continued to heat up to 100-110°C and stirred After 5 hours, DMF was distilled off under reduced pressure, and the residue was cooled to 80°C, and 100 ml of toluene and 50 ml of water were added; the toluene phase was separated and washed successively with 20 ml of 5% dilute hydrochloric acid and 20 ml of saturated sodium bicarbonate; after concentrating the toluene The oil was obtained, and recrystallized once with 15 ml of methanol to obtain 36 g of azoxystrobin, with a content of 98.1% (external standard method), and a yield of 92.2%. the

Application Example 2

In the DMF solution of o-hydroxybenzonitrile obtained in Example 2, add 32 grams (0.095mol, content 95%, provided by Shanghai Heben Pharmaceutical Industry) (E)-2-[2-(6-chloropyrimidine- 4-yloxy)phenyl]-3-methoxymethyl acrylate, 8.28 grams (0.06mol) of anhydrous potassium carbonate, heated to 100-110°C, stirred for 5 hours, evaporated DMF under reduced pressure, and cooled the raffinate To 80°C, add 100 ml of toluene and 50 ml of water; separate the toluene phase, wash it successively with 20 ml of 5% dilute hydrochloric acid and 20 ml of saturated sodium bicarbonate; concentrate the toluene to obtain an oil, and recrystallize once with 15 ml of methanol to obtain 36.5 grams of azoxystrobin, content 98.5% (external standard method), yield 93.9%. the

Application Example 3

In the o-hydroxybenzonitrile DMF solution prepared in Example 3, add 9.25 grams (0.1mol) of epichlorohydrin, 30.36 grams (0.22mol) of anhydrous potassium carbonate, heat up to 80 ° C and stir for 3 hours, and cool to room temperature Add 10.97 grams (0.15mol) of tert-butylamine, stir at room temperature for 6 hours, evaporate excess tert-butylamine and solvent DMF under reduced pressure, add 50 milliliters of ethyl acetate and 15 milliliters of water to the raffinate; separate the organic phase, and use 30 milliliters of saturated brine Wash twice, dry, and concentrate to obtain 25 grams of crude product 2-[3-(1,1-dimethylethylamino)-2-hydroxypropoxyl]benzonitrile (bunirolol), and then use 85 Milliliters of 15% hydrogen chloride/ethanol solution was processed to obtain 26.2 grams of Bunirolol hydrochloride, the content>99% (HPLC), and the yield was 91%. the

Application Example 4

In the o-hydroxybenzonitrile DMF solution prepared in Example 4, add 9.25 grams (0.1mol) of epichlorohydrin, 13.8 grams (0.1mol) of anhydrous potassium carbonate, heat up to 80°C and stir for 3 hours, then cool to room temperature Add 10.97 grams (0.15mol) of tert-butylamine, stir at room temperature for 6 hours, evaporate excess tert-butylamine and solvent DMF under reduced pressure, add 50 milliliters of ethyl acetate and 15 milliliters of water to the raffinate; separate the organic phase, and use 30 milliliters of saturated brine Wash twice, dry, and concentrate to obtain 25.3 grams of crude product 2-[3-(1,1-dimethylethylamino)-2-hydroxypropoxyl]benzonitrile (bunirolol), and then use 85 Milliliters of 15% hydrogen chloride/ethanol solution were treated to obtain 26.7 grams of Bunirolol hydrochloride, the content>99% (HPLC), and the yield was 92.8%. the

Application Example 5

In the DMF solution of o-hydroxybenzonitrile obtained in Example 5, add 32 grams (0.095mol, content 95%, provided by Shanghai Heben Pharmaceutical Industry) (E)-2-[2-(6-chloropyrimidine- 4-yloxy)phenyl]-3-methoxymethyl acrylate, 24.84 grams (0.18mol) of anhydrous potassium carbonate, heated to 50°C, stirred for one hour; then continued to heat up to 100-110°C and stirred for 5 hours , DMF was evaporated under reduced pressure, the raffinate was cooled to 80°C, 100 milliliters of toluene and 50 milliliters of water were added; the toluene phase was separated, washed successively with 20 milliliters of 5% dilute hydrochloric acid and 20 milliliters of saturated sodium bicarbonate; after concentrating the toluene, an oily The product was recrystallized once with 15 milliliters of methanol to obtain 35.8 grams of azoxystrobin, with a content of 98.1% (external standard method), and a yield of 91.7%. the

Application Example 6

In the DMF solution of o-hydroxybenzonitrile obtained in Example 6, add 32 grams (0.095mol, content 95%, provided by Shanghai Heben Pharmaceutical Industry) (E)-2-[2-(6-chloropyrimidine- 4-yloxy)phenyl]-3-methoxymethyl acrylate, 8.28 grams (0.06mol) of anhydrous potassium carbonate, heated up to 100-110°C and stirred for 5 hours, evaporated DMF under reduced pressure, and the raffinate was cooled to 80°C, add 100 ml of toluene and 50 ml of water; separate the toluene phase, wash with 20 ml of 5% dilute hydrochloric acid and 20 ml of saturated sodium bicarbonate successively; concentrate the toluene to obtain an oily substance, recrystallize once with 15 ml of methanol to obtain 36.1 Azoxystrobin, content 98.6% (external standard method), yield 93%. the

Application Example 7

In the o-hydroxybenzonitrile DMF solution prepared in Example 7, add 9.25 grams (0.1mol) of epichlorohydrin, 13.8 grams (0.22mol) of anhydrous potassium carbonate, heat up to 80°C and stir for 3 hours, then cool to room temperature Add 10.97 grams (0.15mol) of tert-butylamine, stir at room temperature for 6 hours, evaporate excess tert-butylamine and solvent DMF under reduced pressure, add 50 milliliters of ethyl acetate and 15 milliliters of water to the raffinate; separate the organic phase, and use 30 milliliters of saturated brine Wash twice, dry, and concentrate to obtain 25.2 grams of crude product 2-[3-(1,1-dimethylethylamino)-2-hydroxypropoxyl]benzonitrile (bunirolol), and then use 85 Milliliters of 15% hydrogen chloride/ethanol solution were treated to obtain 26.4 grams of Bunirolol hydrochloride, the content>99% (HPLC), and the yield was 91.8%. the

The embodiments in the present invention are only used to illustrate the present invention, and do not constitute a limitation to the scope of the claims. Other substantially equivalent substitutions that can be thought of by those skilled in the art are within the protection scope of the present invention. the

Claims (21)

1. the method for the DMF solution of an eco-friendly preparation salicylonitrile is characterized in that, TRIPHOSGENE 99.5 and salicylic amide is added respectively among the DMF, fully reaction.

2. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 1 is characterized in that, described salicylic amide is 1: 0.33～1.0 with the amount of substance ratio of TRIPHOSGENE 99.5.

3. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 2 is characterized in that, described salicylic amide is 1: 0.34～0.5 with the amount of substance ratio of TRIPHOSGENE 99.5.

4. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 1 is characterized in that, temperature of reaction is-20～50 ℃.

5. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 4 is characterized in that, temperature of reaction is 5～15 ℃.

6. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 1 is characterized in that, in DMF, adds TRIPHOSGENE 99.5 earlier, adds salicylic amide again.

7. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 6 is characterized in that said TRIPHOSGENE 99.5 is dissolved in inert solvent earlier, is added among the DMF again.

8. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 1 is characterized in that, in DMF, adds salicylic amide earlier, adds TRIPHOSGENE 99.5 again.

9. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 8 is characterized in that, TRIPHOSGENE 99.5 is dissolved in to add in the lump behind the inert solvent again and is dissolved with among the DMF of salicylic amide.

10. according to the method for the DMF solution of claim 7 and 9 described eco-friendly preparation salicylonitriles, it is characterized in that described inert solvent is selected from hydro carbons, ethers, ketone or ester class inert solvent.

11. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 10 is characterized in that, said hydro carbons inert solvent is selected from alkane, aromatic hydrocarbon or its substitutive derivative.

12. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 10 is characterized in that, said ethers inert solvent is selected from aliphatic ether, aromatic hydrocarbons ether or its substitutive derivative.

13. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 10 is characterized in that, said ketone inert solvent is selected from lower aliphatic ketone or its substitutive derivative.

14. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 10 is characterized in that, said ester class inert solvent is selected from fatty ester, aromatic esters or its substitutive derivative.

15. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 1 is characterized in that, after reaction is accomplished, adds the alkali neutralization, filters the DMF solution that obtains salicylonitrile.

16. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 15 is characterized in that, described alkali comprises a kind of or its mixture in mineral alkali and the organic bases.

17. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 16 is characterized in that, said mineral alkali comprises one or more in the oxide compound, oxyhydroxide, carbonate, supercarbonate of basic metal or earth alkali metal.

18. the method for the DMF solution of eco-friendly preparation salicylonitrile according to claim 16 is characterized in that said organic bases comprises one or more in triethylamine, diethylamine and the aniline.

19. the DMF solution of salicylonitrile is characterized in that, adopts the described method production of the arbitrary claim of claim 1-16.

20. salicylonitrile is characterized in that, adopts the DMF solution of the salicylonitrile of the described method production of the arbitrary claim of claim 1-16, separates obtaining salicylonitrile.

21. the application of the DMF solution of salicylonitrile in synthetic ICIA 5504 and bunitrolol.