A process for the highly selective ammoxidation of aromatic alcohols to aromatic nitriles

Abstract

The application provides a method for one-step conversion of aromatic alcohol into aromatic nitrile, which comprises the following steps: using a metal salt as a catalyst, a hydroxylamine salt as an ammonia source, air or oxygen as an oxidant, and performing an ammoxidation reaction of the aromatic alcohol under light conditions to convert the aromatic alcohol into the aromatic nitrile in one step. The application does not use any expensive or toxic photocatalyst, material or reagent, the raw material is easy to obtain, the operation is simple, the reaction is carried out at normal temperature and pressure, the conditions are mild, and the application has an industrial amplification prospect; and the safety, environmental protection, economy and social benefit of the application have remarkable advantages.

Description

TECHNICAL FIELD

[0001] The present invention relates to the field of organic synthesis, in particular to a process for the highly selective ammoxidation of aromatic alcohols to aromatic nitriles. BACKGROUND

[0002] Nitriles are one of the most important intermediates in organic synthesis, which have been widely used in the synthesis of fine chemicals such as pesticides, pharmaceuticals, dyes, etc. Traditionally, most nitriles are prepared by Sandmeyer reaction (Chem. Rev. 1947, 40(2): 251-277), nucleophilic substitution of halogenated compounds with metal cyanide (Synthetic Communications, 1979, 9(7): 625-630.; J. Org. Chem. 1990, 55(10): 3274-3277) or cyanylation of aryl C-H bond (J. Org. Chem. 1998, 63(23): 8224-8228.; Org. Lett. 2010, 12(11): 2517-2519; Angew. Chem. Int. Ed. 2014, 53(8), 2186-2189.). However, these methods have many defects: stoichiometric toxic metal cyanide as cyanide source; inorganic salts and other by-products are produced, which can cause secondary pollution; poor atom economy and selectivity; harsh reaction conditions (high temperature and high pressure); tedious work-up and high cost, etc. In the past few decades, to avoid the use of toxic metal cyanide, the dehydration of aldoxime (or oxime) (Tetrahedron Lett. 2010, 51(34): 4479-4481; Tetrahedron. 2012, 68(13): 2899-2905; Chin. J. Chem. 2015, 33(9): 1011-1014.), the dehydration of amide (Org. Biomol. Chem. 2004, 2(14): 1979-1986; Chem. Commun. 2009, 40(32): 4883-4885; Chem. Commun. 2010, 46(43): 8243-8245.), transition metal-catalyzed oxidation of primary amine (Chem. Commun. 1996, 20(20): 2343-2344; Catal. Sci. Technol. 2013, 3(10): 2646-2653; ACS Catal. 2015, 5(1): 34-38.) have been widely reported as alternative methods. However, the reaction process often requires the use of phosphorus-containing dehydrating agent or noble metal catalyst, and the reaction often needs to be carried out under harsh reaction conditions. Therefore, it is of great significance to develop green and environmentally friendly synthetic methods to prepare nitriles. Alcohols are potential raw materials for the production of various chemicals due to their low price and easy availability. Therefore, selective oxidation of alcohols to prepare nitriles is a very important reaction in organic synthesis.From a large number of literatures, it can be obtained that the preparation of nitrile compounds from alcohols by oxidation pathway mostly needs various oxidants such as elemental iodine (Bull. Korean Chem. Soc. 2011, 32(12): 4191-4194; Synth. Commun. 2013, 43(1): 52-58.), persulfate (Chem. Lett. 1990, (4): 571-574.), TBHP (Tetrahedron Lett. 2009, 50(18): 2050-2053; Org. Biomol. Chem. 2014, 12(3): 414-417; Chem. Commun. 2015, 51(24): 5085-5088.), DDQ (J. Org. Chem. 2004, 69(7): 2562-2564; Chem. Commun. 2012, 48(44): 5506-5508.) and the like. The use of these oxidants involves complicated operation and harsh reaction conditions (high temperature, high pressure), and these limitations limit their further application. SUMMARY

[0003] In view of the deficiencies in the synthesis of existing aromatic nitriles, the present application provides a method for high-selective aminooxidation of aromatic alcohols to aromatic nitriles, which solves the problems in the background.

[0004] The technical scheme adopted by the present application is: a method for high-selective aminooxidation of aromatic alcohols to aromatic nitriles, characterized by comprising the following steps:

[0005] The aromatic alcohol is subjected to aminooxidation reaction under the conditions of normal temperature and pressure, with a metal salt as a catalyst, a hydroxylamine salt as an ammonia source, and air or oxygen as a catalyst, and is converted into an aromatic nitrile under light irradiation;

[0006] The reaction is represented by the following formula,

[0007]

[0008] In the formula,

[0009] Ar represents a benzene ring or an aromatic heterocycle;

[0010] hv represents light irradiation conditions;

[0011] X is one of t-butyl, phenyl, -OR, -OCOR, halogen (F, Cl), -CF3, -OCF3 or -NHCOR; wherein R is one of H, methyl, ethyl or phenyl.

[0012] Further, the metal salt is specifically one of ferrous sulfate heptahydrate, copper acetate, copper chloride, iron sulfate, ferric chloride, copper bromide, copper iodide, and iron triflate.

[0013] Furthermore, the hydroxylamine salt is specifically one of hydroxylamine hydrochloride and hydroxylamine sulfate.

[0014] Furthermore, the aromatic alcohol is a substituted aromatic alcohol compound or an aromatic heterocyclic methanol compound, wherein the aromatic ring is a benzene ring, a naphthalene ring, or a biphenyl ring with -H, -OH, -OMe, -OEt, -OPh, -NHAc, -Ph, -F, -Cl, -CF3, or -OCF3 substituents;

[0015] Aromatic heterocycle: a five-membered heterocycle containing sulfur, nitrogen, and oxygen, such as thiophene, furan, or pyrazole.

[0016] Furthermore, the aromatic alcohol reaction is carried out in a solvent, and the solvent is one of water, acetonitrile, ethanol, methanol, tetrahydrofuran, N,N-dimethylformamide, or a mixture of two thereof.

[0017] Furthermore, the molar amount of the metal salt is 0.5 to 2.5 times that of the aromatic alcohol.

[0018] Furthermore, the molar amount of the hydroxylamine salt is 0.5 to 3.0 times that of the aromatic alcohol.

[0019] Furthermore, the reaction temperature is 10-60° C., and the aromatic alcohol reaction is carried out under illumination conditions where the wavelength of the light source is in the range of 300-450 nm.

[0020] Furthermore, the reaction is carried out at normal temperature and pressure.

[0021] The beneficial effects of the present invention are: no expensive or toxic photocatalysts, materials or reagents are used, the operation is simple, the conditions are mild, the raw materials are easily available, and it has broad application prospects; it has significant advantages in safety, environmental protection, economy and social benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Schematic diagram of the reaction structure of the present invention. DETAILED DESCRIPTION

[0023] The present invention will be described in detail below with reference to the accompanying drawings and in combination with embodiments. It should be noted that, unless there is a conflict, the embodiments and features in the embodiments of the present application can be combined with each other.

[0024] like Figure 1 As shown, the present application provides a method for converting aromatic alcohols into aromatic nitriles, wherein the aromatic alcohols are highly selectively ammoxidized to aromatic nitriles under normal temperature and pressure, using metal salts as catalysts, hydroxylamine salts as nitrogen sources, and air or oxygen as oxidants under light conditions.

[0025] A method for converting an aromatic alcohol into an aromatic nitrile, comprising the following steps:

[0026] S1, Catalyst dosage ratio: the dosage of metal salt catalyst is 0.5-2.5 times (mol) of the aromatic alcohol;

[0027] S2, Catalyst addition: the metal salt is used as catalyst in the reaction of aromatic alcohol, wherein the metal salt specifically includes one of ferrous sulfate heptahydrate, copper acetate, copper chloride, iron sulfate, ferric chloride, copper bromide, copper iodide, and iron triflate;

[0028] S3, Ammonia source dosage ratio: the dosage of hydroxylamine in the ammonia source is 0.5-3.0 times (mol) of the aromatic alcohol;

[0029] S4, Ammonia source addition: the ammonia source is specifically hydroxylamine salt, including hydroxylamine hydrochloride and hydroxylamine sulfate, and one of them is selected according to the situation;

[0030] S5, Aromatic alcohol reaction solvent: including one or a mixture of two of water, acetonitrile, ethanol, methanol, tetrahydrofuran, and N,N-dimethylformamide;

[0031] S6, Aromatic alcohol reaction light and temperature conditions: the reaction temperature of the aromatic alcohol is 10-60°C, and the reaction of the aromatic alcohol is carried out under the light condition of a light source with a wavelength range of 300-450 nm;

[0032] S7, Synthesis of aromatic nitrile: the product of the high-selectivity ammoxidation reaction of aromatic alcohol is the corresponding aromatic nitrile.

[0033] Combining the above steps:

[0034] Example 1: Synthesis of benzonitrile

[0035] In a 25.0 mL quartz reaction tube containing a built-in magnet, 1.0 mmol of iron sulfate, 1.5 mmol of hydroxylamine hydrochloride, 1.0 mmol of benzyl alcohol, 1.0 mL of water, and 5.0 mL of acetonitrile were sequentially added. A three-way tube was connected to the mouth of the test tube to communicate with oxygen (air). Start stirring, and irradiate the reaction solution with a 50W LED ultraviolet light with a wavelength of 365 nm at room temperature and normal pressure for 48h. Monitor the reaction results by spotting, and stop the reaction when there is no benzyl alcohol. Add 6.0 mL of ethyl acetate to the reaction solution, and wash it thoroughly with water (2.0 mL x 3). Dry the organic layer with anhydrous sodium sulfate, and remove the excess organic solvent on a rotary evaporator. Finally, purify the colorless oil of benzonitrile (76.2 mg, separation yield 74%) by PTLC (EA: PE = 1:10).

[0036] Example 2: Synthesis of 3-phenoxybenzonitrile

[0037] In a 25.0 mL quartz reaction tube with built-in magnetic bar, 1.0 mmol of iron (II) sulfate heptahydrate, 1.5 mmol of hydroxylamine hydrochloride, 1.0 mmol of 3- phenoxybenzyl alcohol, 1.0 mL of water, 5.0 mL of acetonitrile were added in sequence. A three-way tube was connected to the mouth of the test tube to connect the oxygen (air). Start stirring, under normal temperature and pressure, use 50W LED ultraviolet light with wavelength of 350-370nm to irradiate the reaction solution for 60h. Monitor the reaction results by spotting on a plate, stop the reaction when there is no 3-phenoxybenzyl alcohol, add 6.0 mL of ethyl acetate to the reaction solution, and wash with water (2.0 mL x 3) to fully wash the organic layer, dry the organic layer with anhydrous sodium sulfate and remove the excess organic solvent on the rotary evaporator, and finally purify by PTLC (EA:PE = 1:2) to obtain 3-phenoxybenzonitrile (140.2 mg, separation yield 70%) as a colorless oil.

[0038] Example Three: Synthesis of p-Trifluoromethylbenzonitrile

[0039] In a 25.0 mL quartz reaction tube with built-in magnetic bar, 1.0 mmol of iron (II) sulfate heptahydrate, 1.5 mmol of hydroxylamine hydrochloride, 1.0 mmol of 3- phenoxybenzyl alcohol, 1.0 mL of water, 5.0 mL of acetonitrile were added in sequence. A three-way tube was connected to the mouth of the test tube to connect the oxygen (air). Start stirring, under normal temperature and pressure, use 50W LED ultraviolet light with wavelength of 350-370nm to irradiate the reaction solution for 60h. Monitor the reaction results by spotting on a plate, stop the reaction when there is no 3-phenoxybenzyl alcohol, add 6.0 mL of ethyl acetate to the reaction solution, and wash with water (2.0 mL x 3) to fully wash the organic layer, dry the organic layer with anhydrous sodium sulfate and remove the excess organic solvent on the rotary evaporator, and finally purify by PTLC (EA:PE = 1:2) to obtain 3-phenoxybenzonitrile (140.2 mg, separation yield 70%) as a colorless oil.

[0040] Example Four: Synthesis of 4-Methoxybenzonitrile

[0041] In a 25.0 mL quartz reaction tube with built-in magnetic bar, 1.0 mmol of iron (II) sulfate heptahydrate, 1.5 mmol of hydroxylamine hydrochloride, 1.0 mmol of 3- phenoxybenzyl alcohol, 1.0 mL of water, 5.0 mL of acetonitrile were added in sequence. A three-way tube was connected to the mouth of the test tube to connect the oxygen (air). Start stirring, under normal temperature and pressure, use 50W LED ultraviolet light with wavelength of 350-370nm to irradiate the reaction solution for 60h. Monitor the reaction results by spotting on a plate, stop the reaction when there is no 3-phenoxybenzyl alcohol, add 6.0 mL of ethyl acetate to the reaction solution, and wash with water (2.0 mL x 3) to fully wash the organic layer, dry the organic layer with anhydrous sodium sulfate and remove the excess organic solvent on the rotary evaporator, and finally purify by PTLC (EA:PE = 1:2) to obtain 3-phenoxybenzonitrile (140.2 mg, separation yield 70%) as a colorless oil.

[0042] Example Five: Synthesis of 3,4-difluorobenzonitrile

[0043] In a 25.0 mL quartz reaction tube with built-in magnetic bar, 1.0 mmol of copper iodide, 1.5 mmol of hydroxylamine hydrochloride, 1.0 mmol of 3,4-difluorobenzyl alcohol, 1.0 mL of water, 5.0 mL of acetonitrile were added in sequence. A three-way tube was connected to the mouth of the test tube to connect the oxygen (air). Start stirring, under normal temperature and pressure, use 50W LED ultraviolet light with wavelength of 395nm to irradiate the reaction solution for 36h. Monitor the reaction results by spotting on silica gel plate, stop the reaction when there is no 3,4-difluorobenzyl alcohol, add 6.0 mL of ethyl acetate to the reaction solution, and wash with water (2.0 mL x 3) to dryness. The organic layer was dried over anhydrous sodium sulfate and the excess organic solvent was removed on a rotary evaporator, and finally purified by PTLC (EA:PE = 1:10) to obtain white solid 3,4-difluorobenzonitrile (94.6 mg, separation yield 68%).

[0044] Example Six: Synthesis of 2,6-dichlorobenzonitrile

[0045] In a 25.0 mL quartz reaction tube with built-in magnetic bar, 1.0 mmol of iron triflate, 1.5 mmol of hydroxylamine hydrochloride, 1.0 mmol of 2,6-dichlorobenzyl alcohol, 1.0 mL of water, 5.0 mL of acetonitrile were added in sequence. A three-way tube was connected to the mouth of the test tube to connect the oxygen balloon. Start stirring, under normal temperature and pressure, use 50W LED ultraviolet light with wavelength of 350-370nm to irradiate the reaction solution for 36h. Monitor the reaction results by spotting on silica gel plate, stop the reaction when there is no 2,6-dichlorobenzyl alcohol, add 6.0 mL of ethyl acetate to the reaction solution, and wash with water (2.0 mL x 3) to dryness. The organic layer was dried over anhydrous sodium sulfate and the excess organic solvent was removed on a rotary evaporator, and finally purified by PTLC (EA:PE = 1:10) to obtain white solid 2,6-dichlorobenzonitrile (135.9 mg, separation yield 79%).

[0046] Example Seven: Synthesis of 2-cyanothiophene

[0047] In a 25.0 mL quartz reaction tube containing built-in magnetic, 1.0 mmol of copper bromide, 1.5 mmol of hydroxylamine sulfate, 1.0 mmol of 2-thiophenemethanol, 1.0 mL of water, 5.0 mL of acetonitrile were sequentially added. A three-way pipe was connected to the mouth of the test tube to communicate with oxygen (air). Start stirring, irradiate the reaction solution with a 50W LED ultraviolet light of wavelength 365nm at room temperature and normal pressure for 36h. Monitor the reaction results by spotting, stop the reaction when there is no 2-thiophenemethanol, add 6.0 mL of ethyl acetate to the reaction solution, and wash with water (2.0 mL x 3) to dry the organic layer with anhydrous sodium sulfate and remove the excess organic solvent on the rotary evaporator, and finally purify by PTLC (EA: PE = 1:10) to obtain 2-cyanothiophene as an oily liquid (48.0 mg, separation yield 44%).

[0048] Of course, the above description is not a limitation of the present application, and the present application is not limited to the above examples. Changes, modifications, additions or substitutions made by those skilled in the art within the scope of the present application,

[0049] The specification also belongs to the scope of protection of the present application.

Claims

1. Process for the highly selective ammoxidation of aromatic alcohols to aromatic nitriles, characterized in that: The method comprises the following steps: The aromatic alcohol is subjected to an ammoxidation reaction under the light condition at normal temperature and pressure, with the metal salt as a catalyst and the hydroxylamine salt as an ammonia source, so as to be converted into an aromatic nitrile in one step; The reaction formula is represented by the following formula: In the formula, hv represents the light condition; X-Ar is a benzene ring or a naphthalene ring with -OH, -OMe, -OEt, -OPh, -NHAc, -F, -Cl, -CF3, -OCF3 substituents; The metal salt is specifically one of ferrous sulfate heptahydrate, copper acetate, copper chloride, iron sulfate, ferric chloride, copper bromide, copper iodide and iron triflate.

2. The process for the high selective ammoxidation of aromatic alcohols to aromatic nitriles according to claim 1, characterized by: The hydroxylamine salt is specifically one of hydroxylamine hydrochloride and hydroxylamine sulfate.

3. The process for the high selective ammoxidation of aromatic alcohols to aromatic nitriles according to claim 1, characterized by: The aromatic alcohol reaction is carried out in a solvent, and the solvent is one of water, acetonitrile, ethanol, methanol, tetrahydrofuran and N,N-dimethylformamide or a mixture of two thereof.

4. The process for the high selective ammoxidation of aromatic alcohols to aromatic nitriles according to claim 1, characterized by: The molar amount of the metal salt is 0.5-2.5 times that of the aromatic alcohol.

5. The process for the high selective ammoxidation of aromatic alcohols to aromatic nitriles according to claim 2, characterized by: The molar amount of the hydroxylamine salt is 0.5-3.0 times that of the aromatic alcohol.

6. The process for the high selective ammoxidation of aromatic alcohols to aromatic nitriles according to claim 1, characterized by: During the reaction of the aromatic alcohol, the light source has a wavelength range of 300-450 nm.

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