CN103086917B - Synthetic method of aromatic organic cyanide - Google Patents
Synthetic method of aromatic organic cyanide Download PDFInfo
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- CN103086917B CN103086917B CN201310013272.0A CN201310013272A CN103086917B CN 103086917 B CN103086917 B CN 103086917B CN 201310013272 A CN201310013272 A CN 201310013272A CN 103086917 B CN103086917 B CN 103086917B
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Abstract
The invention provides a synthetic method of aromatic organic cyanide. The synthetic method comprises the following steps of: with aromatic halide and cyanoacetic acid as raw materials as well as 1, 2-bis(diphenylphosphino) ethane (DPPE) and lewis acid as catalysts, carrying out reaction in an organic solvent to produce the aromatic organic cyanide. The synthetic method can be widely applied to various aromatic cyanides and is suitable for forming arbitrary aromatic organic cyanide and also suitable for the aromatic halide containing other organic side chains; and with the adoption of the synthetic method, raw materials are cheap and are easy to acquire, the operation is simple, the yield is high, and the synthetic method is suitable for mass production.
Description
Technical field
The present invention relates to a kind of method of synthetic aroma race organic cyanide (Ar-CN).Especially relate to and a kind of use aromatic halides, cyanoacetic acid is raw material, two (diphenylphosphine) ethane of 1,2-and Lewis acid as catalyzer, the method for synthetic aroma race organic cyanide in organic solvent.
Background technology
Aromatic organic cyanide is the very important intermediate of a class in organic synthesis.They are easy to be converted into other useful functional compounds, as aldehyde, ketone, carboxylic acid and derivative thereof etc.In organic compound molecule, introducing cyano group by the formation of C-C is one of mode the most basic in organic synthesis.As everyone knows, the nucleophilic substitution reaction of aliphatic halogenated hydrocarbon and cyano group negative ion is the classical way preparing aliphatics prussiate; The nucleophilic addition of cyano group negative ion to carbonyl compound and imines is the important method of synthesizing α-hydroxyl (ammonia) base prussiate.In addition, sandmeyer reaction and Luo Senmengde-von Braun reaction are the traditional methods of synthetic aroma race prussiate.But these two kinds of methods all need to wait the cuprous cyanide of amount of substance and the reaction conditions of harshness.
The people such as Martin use (NH
4)
2[(VO)
3(P
2o
7)
2] prepare 3,4-dichlorobenzonitrile as ammoxidation catalyst, productive rate is only 50%, is difficult to the requirement reaching suitability for industrialized production.In addition, this catalytic mechanical intensity is not high, and Catalyst Production cost is higher, cannot be used for fluidized-bed reactor yet.This method requires equipment high temperature high voltage resistant, and cost is higher.
The people such as Liu Qibo take phenylformic acid as raw material, and through amidation, then with phosphorus pentachloride 200 DEG C dehydration, underpressure distillation obtains cyanophenyl, and total coreaction 10 hours, productive rate is only 64%.This method reaction times is longer, and synthesis step is more, and temperature of reaction is too high, and reaction conditions is difficult to control.
The people such as Jun are with 3,4-Dihydroxy benzaldehydes for raw material, and formic acid silica dioxide is catalyzer, react under microwave with oxammonium hydrochloride, and yield is 70%.The shortcoming of this method is that difficulty or ease realize industrialization.
People's reported first such as Takagi cyanogenation of palladium chtalyst aryl iodide and bromide. the work of this initiative led the cyanogenation of domestic and international organic chemists to transition metal-catalyzed halogenated aryl hydrocarbon to conduct extensive research.But it is higher that this reaction uses transition-metal catalyst price, is therefore not suitable for industrialization.
The people such as Anderson finds in the system of palladium chtalyst aryl halide cyanogenation, and add the efficiency that the mantoquita of catalytic amount or zinc salt greatly can improve reaction, corresponding cyaniding product yield is 71% ~ 92%.
Therefore, need a kind of method that raw material is cheap and easy to get, productive rate is high, simple to operate, the needs of scale operation can be more suitable for like this
Summary of the invention
The object of the present invention is to provide a kind of synthetic method of aromatic organic cyanide, a kind of raw material be cheap and easy to get, productive rate is high, simple to operate, be applicable to the method for scale operation aromatic organic cyanide (Ar-CN).
For solving the problems of the technologies described above, the technical solution adopted in the present invention is: a kind of synthetic method of aromatic organic cyanide, with aromatic base halogenide and cyanoacetic acid for raw material, with 1, two (diphenylphosphine) ethane (i.e. DPPE) of 2-and Lewis acid are as catalyzer, and reaction generates aromatic organic cyanide in organic solvent; Its reaction formula is:
In formula, X is Cl, Br, I etc.; R is organic side chain.
Its concrete steps are: add 1 successively in a reservoir, 2-two (diphenylphosphine) ethane, organic solvent, aromatic base halogenide, cyanoacetic acid, Lewis acid, the lower reaction of backflow, after TLC tracking reaction terminates, filtering catalyst, removal of solvent under reduced pressure, obtains thick liquid, recrystallization purifying in ethanol, obtains product.
Described reflux time is 2 ~ 5h.
Described back flow reaction temperature is 50-150 DEG C.
Described cyanoacetic acid and the halid mol ratio 1 ~ 1.5:1 of aromatic base.
Described aromatic base halogenide can be chlorobenzene, bromobenzene, iodobenzene or the aromatic base halogenide containing any organic side chain; In reaction formula, R is organic side chain, and can be arbitrary organic side chain, and X is Cl, Br, I.
Described Lewis acid is aluminum chloride, zinc chloride, iron trichloride or boron trifluoride; Preferred zinc chloride.
Described solvent is arbitrary organic solvent, organic solvent is preferably toluene, dioxane, tetrahydrofuran (THF) (THF), methyl-sulphoxide, ethyl acetate, methyl-sulphoxide, methyl alcohol, N, one in dinethylformamide (DMF), acetone, N-methylmorpholine, N-Methyl pyrrolidone, methylene dichloride etc., preferred acetone or dipole solvent etc.
Compared with the synthetic method of existing aromatic organic cyanide, the present invention has following outstanding advantages and technological achievement:
1. can be widely applied to various aromatic chlorinated thing;
2. catalyzer is cheap, easily obtains;
3. completed by a step, simple to operate, do not need ultralow or ultrahigh-temperature;
4. many kinds of organic solvents all efficiently can complete reaction.
In addition, the present invention is not only suitable for forming arbitrary aromatic organic cyanide, and is suitable for the aromatic halide containing other organic side chains.
Embodiment
Further illustrate the present invention below in conjunction with embodiment, but embodiment is only the present invention is described, instead of is limited.
Example 1: add 20 mg1 successively in the round-bottomed flask of 25mL, two (diphenylphosphine) ethane of 2-, the p-isopropyl chlorobenzene of the DMSO of 15 mL, 5mmol, the cyanoacetic acid of 6 mmol, and 20 zinc chloride of mg, make it back flow reaction 5h, temperature maintains 50-80 DEG C, after TLC tracking reaction terminates, filtering catalyst, removal of solvent under reduced pressure, obtains the thick product of thick white.Recrystallization purifying in ethanol, obtains product, productive rate 89.2%.
Example 2: add 20 mg 1 in the round-bottomed flask of 25mL successively, two (diphenylphosphine) ethane of 2-, the THF of 10 mL, 5mmol to tertiary butyl bromobenzene, the cyanoacetic acid of 6.5mmol, and 25 iron trichlorides of mg, make it back flow reaction 3h, temperature maintains 80-100 DEG C, after TLC tracking reaction terminates, filtering catalyst, removal of solvent under reduced pressure, add 40 mL methylene dichloride, wash with 2 × 10mL, discard water layer, organic phase uses the NaOH solution of 20mL 1 mol/L respectively, 10mL saturated nacl aqueous solution washs, underpressure distillation removing methylene dichloride, obtain white viscous liquid.Obtain the thick product of thick white.Recrystallization purifying in ethanol, obtains product, productive rate 92.8%.
Example 3: add 20 mg 1 in the round-bottomed flask of 25mL successively, two (diphenylphosphine) ethane of 2-, the toluene of 10 mL, 5mmol to tertiary butyl iodobenzene, the cyanoacetic acid of 5.5 mmol, and 20 aluminum chlorides of mg, make it back flow reaction 2 h, temperature maintains 120-150 DEG C, after TLC tracking reaction terminates, filtering catalyst, removal of solvent under reduced pressure, add 40 mL methylene dichloride, wash with 2 × 10mL, discard water layer, organic phase uses the NaOH solution of 20mL 1 mol/L respectively, 10mL saturated nacl aqueous solution washs, underpressure distillation removing methylene dichloride, obtain white viscous liquid.Obtain the thick product of thick white.Recrystallization purifying in ethanol, obtains product, productive rate 90.5%.
Example 4: add 20 mg 1 in the round-bottomed flask of 25mL successively, two (diphenylphosphine) ethane of 2-, the DMF of 10 mL, 5mmol to tertiary butyl bromobenzene, the cyanoacetic acid of 5 mmol, and 20 zinc chloride of mg, make it back flow reaction 3 h, temperature maintains 80-120 DEG C, after TLC tracking reaction terminates, filtering catalyst, removal of solvent under reduced pressure, add 40 mL methylene dichloride, wash with 2 × 10mL, discard water layer, organic phase uses the NaOH solution of 20mL 1 mol/L respectively, 10mL saturated nacl aqueous solution washs, underpressure distillation removing methylene dichloride, obtain brown viscous liquid.Obtain the thick product of thick white.Recrystallization purifying in ethanol, obtains product, productive rate 93.7%.
Example 5: add 20 mg 1 in the round-bottomed flask of 25mL successively, two (diphenylphosphine) ethane of 2-, the toluene of 10 mL, the p-Nitrophenyl chloride of 5mmol, the cyanoacetic acid of 7 mmol, and 25 iron trichlorides of mg, make it back flow reaction 3.5 h, temperature maintains 80-120 DEG C, after TLC tracking reaction terminates, filtering catalyst, removal of solvent under reduced pressure, add 40 mL methylene dichloride, wash with 2 × 10mL, discard water layer, organic phase uses the NaOH solution of 20mL 1 mol/L respectively, 10mL saturated nacl aqueous solution washs, underpressure distillation removing methylene dichloride, obtain white viscous liquid.Obtain the thick product of thick white.Recrystallization purifying in ethanol, productive rate 87.5%.
Example 6: add 20 mg 1 in the round-bottomed flask of 25mL successively, two (diphenylphosphine) ethane of 2-, the acetone of 10 mL, 5 mmol to methoxyl group iodobenzene, the cyanoacetic acid of 7.5 mmol, and 20 aluminum chlorides of mg, make it back flow reaction 4 h, temperature maintains 60-90 DEG C, after TLC tracking reaction terminates, filtering catalyst, removal of solvent under reduced pressure, add 40 mL methylene dichloride, wash with 2 × 10mL, discard water layer, organic phase uses the NaOH solution of 20mL 1 mol/L respectively, 10mL saturated nacl aqueous solution washs, underpressure distillation removing methylene dichloride, obtain white viscous liquid.Obtain the thick product of thick white.Recrystallization purifying in ethanol, productive rate 91.8%.
Example 7: add 10mg 1 successively in the round-bottomed flask of 25mL, two (diphenylphosphine) ethane of 2-, the dioxane of 15mL, the p-isopropyl bromobenzene of 5mmol, the cyanoacetic acid of 6 mmol, and 20 boron trifluorides of mg, make it back flow reaction 2.5 h, temperature maintains 120-130 DEG C, after TLC tracking reaction terminates, filtering catalyst, removal of solvent under reduced pressure, add 40 mL methylene dichloride, wash with 2 × 10mL, discard water layer, organic phase uses the NaOH solution of 20mL 1 mol/L respectively, 10mL saturated nacl aqueous solution washs, underpressure distillation removing methylene dichloride, obtain white viscous liquid.Obtain the thick product of thick white.Recrystallization purifying in ethanol, obtains product, productive rate 88.5%.
Claims (1)
1.
a kind of synthetic method of aromatic organic cyanide, it is characterized in that: with aromatic base halogenide and cyanoacetic acid for raw material, with 1, two (diphenylphosphine) ethane (i.e. DPPE) of 2-and Lewis acid are as catalyzer, and reaction generates aromatic organic cyanide in organic solvent; Its reaction formula is:
；
Be specially: in the round-bottomed flask of 25mL, add 20 mg 1 successively, two (diphenylphosphine) ethane of 2-, the DMF of 10 mL, 5mmol to tertiary butyl bromobenzene, the cyanoacetic acid of 5 mmol, and 20 zinc chloride of mg, make it back flow reaction 3 h, temperature maintains 80-120 DEG C, after TLC tracking reaction terminates, filtering catalyst, removal of solvent under reduced pressure, add 40 mL methylene dichloride, wash with 2 × 10mL, discard water layer, organic phase uses the NaOH solution of 20mL 1 mol/L respectively, 10mL saturated nacl aqueous solution washs, underpressure distillation removing methylene dichloride, obtain brown viscous liquid, recrystallization purifying in ethanol, obtains product.
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| CN101717350A (en) * | 2009-12-08 | 2010-06-02 | 南京工业大学 | Synthetic method of aryl cyanide in water solution |
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Non-Patent Citations (3)
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| Ethyl Cyanoacetate: A New Cyanating Agent for the Palladium-Catalyzed Cyanation of Aryl Halides;Shuyan Zheng等;《Organic Chemistry》;20120711;第14卷(第14期);第3646页表格2 * |
| Novel Trans-Spanned Palladium Complexes as Efficient Catalysts in Mild and Amine-Free Cyanation of Aryl Bromides under Air;Olga Grossman等;《Organic Chemistry》;20060222;第8卷(第6期);第1189-1191页 * |
| 对正烷基氰基苯的合成;董兆恒等;《浙江化工》;20011231;第32卷(第3期);第27-28页 * |
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