Chlorination method of iron-catalyzed carbonyl compound alpha-H

Abstract

The invention provides a chlorination method of an iron-catalyzed carbonyl compound alpha-H, and relates to a carbonyl alpha-Cl substitution method taking iron as a catalyst and inorganic salt as a chlorinating agent. Comprising the following steps: S1, putting a solution of inorganic salt chloride and inorganic acid or organic acid into a photoreactor, and then adding an iron catalyst and a carbonyl compound; s2, under the condition of room temperature, carrying out catalytic reaction under the illumination of sunlight or a 300W xenon lamp or an LED lamp; and S3, standing the reaction solution, washing the organic phase with a saturated saline solution, drying the organic phase, and separating and purifying the dried organic phase to obtain a corresponding organic halogenated product. The carbonyl compound alpha-H chlorination method provided by the invention has the characteristics of low cost, high product selectivity, easiness in separation and the like, can be used for large-scale production, and provides a brand-new and feasible green way for formation of C-Cl.

Description

Technical Field

[0001] The invention relates to a general reaction method of organic matter, in particular to a green, efficient and highly selective synthesis method of chlorocarbonyl α-H using iron as a catalyst and inorganic salt chloride as a chlorinating agent, belonging to the technical field of chemical industry. Background Art

[0002] α-Chloroketones (aldehydes) are a representative class of halogenated hydrocarbons. They are important intermediates for fine chemicals (such as pharmaceuticals, agrochemicals, and polymers) and are fundamental building blocks in organic synthesis. Because chlorination can improve the physicochemical properties of drug molecules, imparting unique physiological and pharmacological activities, α-chloroketones (aldehydes) also hold broad development prospects in the pharmaceutical field.

[0003] The traditional method for the chlorination of carbonyl α-C(sp3)-H compounds uses chlorine gas as the chlorinating agent. Chlorine is produced in the chlor-alkali industry, and its production, transportation, and use are not only dangerous but also have serious environmental impacts. Furthermore, this traditional chlorination process only achieves a maximum chlorine utilization rate of 50%, with the remaining 50% forming hydrogen chloride as a byproduct or being absorbed by the alkali and converted into sodium chloride. However, these chlorination methods often suffer from harsh reaction conditions, expensive chemical reagents, and the production of α,α-dichloro products. This approach is neither atom-economical nor meets the basic requirements of sustainable chemical processes. Therefore, developing a method for the direct chlorination of carbonyl α-H compounds using inorganic chlorides as the chlorine source in the absence of strong oxidants would overcome the theoretical barrier of 50% maximum chlorine utilization while ensuring green chemical development, and would have significant technical and economic value.

[0004] Nano-precious metal / semiconductor photocatalysts coupled with visible light catalysis can achieve chemical transformations at room temperature that are inaccessible to traditional methods. These include reactions such as photocatalytic water splitting to produce hydrogen, oxidation of alkanes, oxidation of alkenes, oxidation of alcohols, direct oxidative hydroxylation of aromatic rings, and oxidation of fused rings. While the chlorination of α-H groups of cycloalkanes and alkyl aromatics using inorganic chlorides as chlorinating agents has been reported, the chlorination of α-H groups of carbonyl compounds using readily available and inexpensive iron as a visible light catalyst and inorganic chlorides as the chlorine source under light irradiation with high conversion and selectivity has not yet been reported. Summary of the Invention

[0005] In response to the above problems, the present invention provides an iron-catalyzed chlorination method for carbonyl compounds α-H, which saves reaction costs and makes the product more selective and easier to separate.

[0006] To achieve the above object, the technical solution of the present invention is a method for chlorinating a carbonyl compound α-H catalyzed by iron, and the reaction process of the chlorinating method is shown in the following formula:

[0007]

[0008] The carbonyl compound containing α-H is selected from the following group: R 1 or R 2 It is any one of H, alkyl aromatic hydrocarbon group, heterocyclic hydrocarbon group, aliphatic hydrocarbon group and alicyclic group.

[0009] Further, the following steps are included:

[0010] S1: placing an inorganic salt chloride and an inorganic acid or organic acid as a chlorine source, an organic solvent and an α-H-containing carbonyl compound in a photoreactor;

[0011] S2: While stirring, under sunlight or 300W xenon lamp or LED light, add iron catalyst in batches to catalyze the reaction. After the reaction period, stop stirring;

[0012] S3: After the reaction solution is allowed to stand, the organic phase is washed and dried, and the dried organic phase is subjected to rectification or recrystallization separation, or chromatography purification to obtain the corresponding organic halogenated product.

[0013] Furthermore, in step S1, the inorganic salt chloride serving as a chlorine source is any one of magnesium chloride, sodium chloride, potassium chloride, calcium chloride, lithium chloride, ammonium chloride, and ferric chloride.

[0014] Furthermore, in step S1, the carbonyl compound containing α-H is a ketone or an aldehyde;

[0015] wherein the ketone or aldehyde containing α-H is selected from aliphatic ketones, alicyclic ketones, alkyl aryl ketones, aliphatic aldehydes or alicyclic aldehydes;

[0016] Among them, aliphatic ketones include methyl ketones;

[0017] Among them, the alicyclic ketones are cyclopentanone, cyclohexanone, cycloheptanone or their benzo derivatives, aromatic heterocyclic alicyclic ketones and aliphatic condensed ring derivatives, the above alicyclic ketones also include but are not limited to camphor ketone, anisone and macrocyclic ketones, macrocyclic ketones include but are not limited to musk ketone;

[0018] Wherein, the alkyl aryl ketone is acetophenone, aromatic heterocyclic ethyl ketone, propiophenone, aromatic heterocyclic ethyl ketone series compounds or aromatic ring substituted derivatives, which include but are not limited to halogenated aryl, alkoxyaryl, nitroaryl, aminoaryl, sulfonylaryl, tertiary alkyl aryl;

[0019] The halogenated aryl group includes fluoro, chloro, bromo or iodo.

[0020] Furthermore, in step S1, the inorganic acid used is any one of hydrochloric acid, sulfuric acid, phosphoric acid or sulfonic acid; the organic acid used is any one of acetic acid, benzoic acid, chloroacetic acid, trichloroacetic acid, and trifluoroacetic acid.

[0021] Furthermore, the sulfonic acid is selected from any one of methanesulfonic acid, trifluoromethanesulfonic acid, chlorosulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, nitrobenzenesulfonic acid or benzene disulfonic acid.

[0022] Furthermore, in step S1, the iron catalyst used is selected from any one of iron powder, ferric chloride, ferrous chloride, ferric sulfate, ferrous sulfate, ferric nitrate, ferrosoferric oxide, ferric oxide, and iron salt hydrate.

[0023] Furthermore, in step S1, the organic solvent is selected from one or any two of acetonitrile, acetonitrile aqueous solution, DMF, chlorobenzene, fluorobenzene, 1,4-dioxane or 1,2-dichloroethane.

[0024] Furthermore, in step S1, the molar ratio of the added inorganic salt chloride ion to the reaction substrate is between 0.5:1 and 28:1.

[0025] Furthermore, in step S1, the molar ratio of the added organic acid or inorganic acid to the chloride ion in the inorganic salt chloride is between 1:1-1:10; in the reaction, the molar ratio of the amount of the iron catalyst used to the α-H-containing carbonyl compound is between 1.0-40%.

[0026] The beneficial effects of the iron-catalyzed chlorination method of carbonyl compounds α-H of the present invention are:

[0027] Iron is one of the most abundant elements in the Earth's crust. Iron, its salts, and its complexes are common catalysts and are environmentally friendly, renewable, low-cost, and high-value-added. In response to the current scientific challenges and technical bottlenecks in the CH halogenation of organic compounds, the present invention develops a novel chlorination pathway. This pathway directly uses inorganic salts as chlorinating agents and utilizes visible light, sunlight, or LED light in conjunction with iron for synergistic catalysis, resulting in highly selective chlorination of carbonyl α-H bonds. This allows for the low-cost conversion of inorganic chlorides into organic chlorides, providing a new, simpler, and more effective strategy for resolving the chlorine balance dilemma in chlorine-related industrial systems.

[0028] The present invention is in a heterogeneous system, with the chloride ions in the inorganic salt chloride as the chlorine source, and Fe as the photocatalyst. Under the radiation of sunlight, visible light or LED light, the valence electrons receive photons and undergo electronic transitions, resulting in the formation of photogenerated electrons and holes. In this way, the electrons of the chloride ions are transferred to the holes to generate chlorine free radicals to trigger free radical reactions. Subsequently, the chloride ions of the inorganic salts are then supplemented with chloride ions on the catalyst surface to maintain the composition of the catalyst. The driving force of the reaction comes from the hydrogen peroxide formed by the reduction of the oxygen molecules dissolved in the reaction system by the generated photogenerated electrons, and then the latter oxidize the chloride ions in situ to form chlorine molecules under acidic conditions to promote the reaction. Since the speed of photogenerated electron formation is relatively slow, the concentration of chlorine is ultimately extremely low, so the speed of chlorination can be effectively controlled, so that the method provided by the present invention has extremely high selectivity.

[0029] The method for chlorinating the carbonyl compound α-H provided by the present invention has low cost, simple and easy-to-operate equipment, high product selectivity, easy separation, and can be produced on a large scale. It is a new, environmentally friendly, highly selective, low-energy, and feasible green approach for the chlorination of organic matter and has very good industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0031] Figure 1 This is the GC-MS chart of acetophenone-2-chloroacetophenone.

[0032] Figure 2 2-chloroacetophenone 1 HNMR spectrum.

[0033] Figure 3 2-chloroacetophenone 13 CNMR image.

[0034] Figure 4 This is the GC-MS chart of 4-chloroacetophenone-2,4-dichloroacetophenone.

[0035] Figure 5 2,4-dichloroacetophenone 1 HNMR spectrum.

[0036] Figure 6 2,4-dichloroacetophenone 13 CNMR image.

[0037] Figure 7 This is the GC-MS chart of cyclohexanone-chlorocyclohexanone.

[0038] Figure 8 For chlorocyclohexanone 1 HNMR spectrum.

[0039] Figure 9 For chlorocyclohexanone 13 CNMR image.

[0040] Figure 10 This is the GC-MS chart of pinacolone-chloropinacolone.

[0041] Figure 11 for chloropinacolone 1 HNMR spectrum.

[0042] Figure 12 for chloropinacolone 13 CNMR image. DETAILED DESCRIPTION

[0043] The following is a clear and complete description of the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings in the embodiments of the present invention. In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention can also be implemented in other ways different from those described herein, and those skilled in the art can make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0044] A technical solution for an iron-catalyzed chlorination method of carbonyl compounds α-H is as follows. The reaction process of the chlorination method is shown in the following formula:

[0045]

[0046] The carbonyl compound containing α-H is selected from the following group: R 1 or R 2 It is any one of H, alkyl aromatic hydrocarbon group, heterocyclic hydrocarbon group, aliphatic hydrocarbon group and alicyclic group.

[0047] The steps include:

[0048] S1: placing an inorganic salt chloride and an inorganic acid or organic acid as a chlorine source, an organic solvent and an α-H-containing carbonyl compound in a photoreactor;

[0049] Wherein, the inorganic salt chloride as a chlorine source is any one of magnesium chloride, sodium chloride, potassium chloride, calcium chloride, lithium chloride, ammonium chloride, and ferric chloride;

[0050] The carbonyl compound containing α-H is a ketone or an aldehyde; preferably, the ketone or aldehyde containing α-H is selected from aliphatic ketones, alicyclic ketones, alkylaryl ketones, aliphatic aldehydes or alicyclic aldehydes; wherein the aliphatic ketone includes methyl ketone;

[0051] Among them, the alicyclic ketones are cyclopentanone, cyclohexanone, cycloheptanone or their benzo derivatives, aromatic heterocyclic alicyclic ketones and aliphatic condensed ring derivatives, the above alicyclic ketones also include but are not limited to camphor ketone, anisone and macrocyclic ketones, macrocyclic ketones include but are not limited to musk ketone;

[0052] Wherein, the alkyl aryl ketone is acetophenone, aromatic heterocyclic ethyl ketone, propiophenone, aromatic heterocyclic ethyl ketone series compounds or aromatic ring substituted derivatives, which include but are not limited to halogenated aryl, alkoxyaryl, nitroaryl, aminoaryl, sulfonylaryl, tertiary alkyl aryl;

[0053] The halogenated aryl group includes fluoro, chloro, bromo or iodo.

[0054] The inorganic acid used is any one of hydrochloric acid, sulfuric acid, phosphoric acid or sulfonic acid; the organic acid used is any one of acetic acid, benzoic acid, chloroacetic acid, trichloroacetic acid and trifluoroacetic acid;

[0055] The sulfonic acid is selected from any one of methanesulfonic acid, trifluoromethanesulfonic acid, chlorosulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, nitrobenzenesulfonic acid or benzene disulfonic acid;

[0056] The iron catalyst used is selected from any one of iron powder, ferric chloride, ferrous chloride, ferric sulfate, ferrous sulfate, ferric nitrate, ferrosoferric oxide, ferric oxide, and iron salt hydrate;

[0057] The organic solvent is selected from one or any two of acetonitrile, acetonitrile aqueous solution, DMF, chlorobenzene, fluorobenzene, 1,4-dioxane or 1,2-dichloroethane;

[0058] The molar ratio of the added inorganic salt chloride ion to the reaction substrate is between 0.5:1 and 28:1;

[0059] The molar ratio of the added organic acid or inorganic acid to the chloride ion in the inorganic chloride salt is between 1:1 and 1:10. In the reaction, the molar ratio of the amount of the iron catalyst used to the α-H-containing carbonyl compound is between 1.0 and 40%.

[0060] S2: While stirring, under sunlight or 300W xenon lamp or LED light, add iron catalyst in batches to catalyze the reaction. After the reaction period, stop stirring;

[0061] S3: After the reaction solution is allowed to stand, the organic phase is washed and dried, and the dried organic phase is subjected to rectification or recrystallization separation, or chromatography purification to obtain the corresponding organic halogenated product.

[0062] Example 1 Chlorination of acetophenone

[0063] Take 0.07g (1.2mmol) of magnesium chloride, 5.0mL of acetonitrile, 0.3ml (5.0mol) of glacial acetic acid, and 0.08mL (0.6mmol) of acetophenone and add them to the photoreactor in sequence; while stirring, add 0.010g of ferric chloride catalyst, and under the irradiation of LED white light, stir and react at room temperature for 3h; track the reaction by gas chromatography; after the reaction solution is allowed to stand, add 30ml of saturated brine, extract with ethyl acetate, wash with water and saturated brine, dry the organic phase, and purify by column chromatography to precipitate a white solid with mp.54-57℃. Samples were taken and analyzed by GS, the conversion rate was 89%, no polychlorinated products were detected, and the yield was 88%. Figure 1 GC-MS chart of a mixture of acetophenone and chloromethylacetophenone.

[0064] Example 2 Chlorination of acetophenone

[0065] Take 0.22g (3.6mmol chloride ion) of sodium chloride and 0.12mL (3.6mmol) of concentrated hydrochloric acid, 5.0mL of acetonitrile, and 0.08mL (0.6mmol) of acetophenone and add them to the photoreactor in sequence; under stirring, add 0.012g of ferric chloride catalyst, turn on the LED 400nm light source, and react at room temperature for 8h; track the reaction with gas chromatography; after the reaction solution is allowed to stand, add 30ml of saturated brine, extract with ethyl acetate, wash with water and saturated brine, dry the organic phase, and purify by column chromatography to precipitate a white solid with mp.54-57℃. Samples were taken and analyzed by GS, with a conversion rate of 87%, no polychlorinated products detected, and a yield of 85%. Figure 2 2-chloroacetophenone 1 HNMR spectrum.

[0066] Example 3 Chlorination of acetophenone

[0067] 0.07 g (1.2 mmol) of magnesium chloride, 5.0 mL of acetonitrile, 0.196 g (2.0 mmol) of phosphoric acid, and 0.08 mL (0.6 mmol) of acetophenone were added sequentially to a photoreactor. With stirring, 0.01 g of ferrous chloride catalyst was added, and a 420 nm LED light source was used. The reaction was allowed to react at room temperature for 8 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 30 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by column chromatography to precipitate a white solid. A sample was taken and analyzed by GC, revealing an 87% conversion rate, no polychlorinated products, and an 85% yield. Figure 3 2-chloroacetophenone 13 CNMR image.

[0068] Example 4 Chlorination of acetophenone

[0069] 0.175 g (3.0 mmol chloride ion) of calcium chloride, 0.12 mL (2.0 mmol) of hydrochloric acid, 5.0 mL of acetonitrile, and 0.06 mL (0.5 mmol) of acetophenone were added sequentially to a photoreactor. With stirring, 0.015 g of ferric nitrate catalyst was added, and a 445 nm LED light source was used. The reaction was allowed to react at room temperature for 8 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 30 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by column chromatography to precipitate a white solid with an mp of 54-57°C. A sample was analyzed by GC, revealing a 97% conversion rate, no polychlorinated products, and a 95% yield.

[0070] Example 5 Chlorination of acetophenone

[0071] 0.05 mg (1.0 mmol) of magnesium chloride, 0.053 mL (1.0 mmol) of acetic acid, 5.0 mL of acetonitrile, and 0.06 mL (0.5 mmol) of acetophenone were added to a photoreactor in sequence. While stirring, 0.015 g of ferric acetate iron catalyst was added. A 450 nm LED light source was turned on and the reaction was allowed to proceed at room temperature for 6 h. The reaction was monitored by gas chromatography.

[0072] After the reaction mixture was allowed to stand, 30 ml of saturated brine was added and extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by column chromatography to precipitate a white solid with an mp of 54-57°C. Samples were analyzed by GC, revealing a conversion of 95%, no polychlorinated products detected, and a yield of 92%.

[0073] Example 6 Chlorination of acetophenone

[0074] 0.05 mg (1.0 mmol) of magnesium chloride, 0.158 g (1.0 mmol) of benzenesulfonic acid, 5.0 mL of acetonitrile, and 0.06 mL (0.5 mmol) of acetophenone were added to a photoreactor in this order. With stirring, 0.015 g of ferrosoferric oxide catalyst was added, and a 470 nm LED light source was used. The reaction was allowed to react at room temperature for 24 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 30 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by column chromatography to precipitate a white solid with an mp of 54-57°C. A sample was analyzed by GC, revealing an 81% conversion rate, no polychlorinated products, and a 78% yield.

[0075] Example 7 Chlorination of acetophenone

[0076] 0.05 mg (1.0 mmol) of magnesium chloride, 0.189 g (2.0 mmol) of chloroacetic acid, 5.0 mL of acetonitrile, and 0.06 mL (0.5 mmol) of acetophenone were added to a photoreactor in this order. With stirring, 0.015 g of ferric oxide catalyst was added, and a 365 nm LED light source was used. The reaction was allowed to react at room temperature for 6 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 30 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by column chromatography to precipitate a white solid with an mp of 54-57°C. A sample was taken and analyzed by GC, revealing an 83% conversion rate, no polychlorinated products, and an 80% yield.

[0077] Example 8 Chlorination of acetophenone

[0078] A solution of 0.054 mg (1.0 mmol) of ammonium chloride, 0.053 mL (1.0 mmol) of acetic acid, 5.0 mL of acetonitrile, and 0.06 mL (0.5 mmol) of acetophenone was added to a photoreactor. With stirring, 0.015 g of ferric sulfate catalyst was added, and a 470 nm LED light source was used. The reaction was allowed to react at room temperature for 12 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 30 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by column chromatography to precipitate a white solid with an mp of 54-57°C. A sample was analyzed by GC, revealing an 88% conversion rate, no polychlorinated products, and an 86% yield.

[0079] Example 9 Chlorination of acetophenone

[0080] 8.1 mg (83.0 mmol) of magnesium chloride, 9.7 mL (166.0 mmol) of acetic acid, 130 mL of acetonitrile, and 10.0 mL (83.0 mmol) of acetophenone were added sequentially to a photoreactor. With stirring, 4.0 g of iron powder catalyst was added, and a 300 W xenon lamp was turned on. The reaction was allowed to react at room temperature for 6 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 60 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by rectification to precipitate a white solid with an mp of 54-57°C. A sample was taken and analyzed by GC, revealing an 89% conversion rate, no polychlorinated products, and an 84% yield.

[0081] Example 10 Chlorination of 3-acetylpyridine

[0082] 8.0 mL of brine, 9.7 mL (166.0 mmol) of acetic acid, 130 mL of acetonitrile, and 83.0 mmol of 3-acetylthiophene were added to a photoreactor in this order. With stirring, 4.0 g of ferric chloride catalyst was added, and a 300 W xenon lamp was turned on. The reaction was allowed to react at room temperature for 6 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 60 mL of saturated brine was added. The aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with water and saturated brine, dried, and purified by rectification to precipitate a white solid. A sample was taken and analyzed by GC, revealing an 89% conversion rate, no polychlorinated products, and an 84% yield.

[0083] Example 11 Chlorination of acetonapthone

[0084] 0.228 mg (3.0 mmol) of potassium chloride, 0.079 mL (1.5 mmol) of sulfuric acid, 5.0 mL of acetonitrile, and 0.5 mmol of β-acetonapthone were added to a photoreactor in this order. With stirring, 0.015 g of iron powder catalyst was added, and a 365 nm LED light source was used. The reaction was allowed to react at room temperature for 5 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 60 mL of saturated brine was added. The aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with water and saturated brine, dried, and purified by rectification to precipitate a white solid. A sample was taken and analyzed by GC, revealing an 83% conversion rate, no polychlorinated products, and an 81% yield.

[0085] Example 12 Chlorination of p-chloroacetophenone

[0086] Take 0.07g (1.2mmol) lithium chloride, 3.0mL 1,4-dioxane, 0.5mL (5.0mmol) concentrated hydrochloric acid, 0.09mL (0.6mmol) p-chloroacetophenone, add p-chloroacetophenone and add the photoreactor in sequence; while stirring, add 0.015g nano-ferroferric oxide photocatalyst, under the irradiation of LED light, stir and react at room temperature for 3h; track the reaction with gas chromatography; after the reaction solution is allowed to stand, add 50ml saturated brine, extract with ethyl acetate, wash with water and saturated brine, dry the organic phase, purify by column chromatography, and precipitate a white solid product with mp.20-21℃. Samples were analyzed by GS, the conversion rate was 78%, no polychlorinated products were detected, and the yield was 90%. Figure 4 This is the GC-MS chart of 4-chloroacetophenone-2,4-dichloroacetophenone. Figure 5 2,4-dichloroacetophenone 1 HNMR spectrum.

[0087] Example 13 Chlorination of p-chloroacetophenone

[0088] 0.05 mg (1.0 mmol) of magnesium chloride, 3.0 mL of 1,4-dioxane, 0.5 mL (5.0 mmol) of trifluoroacetic acid, and 0.09 mL (0.6 mmol) of p-chloroacetophenone were sequentially added to a photoreactor. While stirring, 0.015 g of ferric chloride catalyst was added. Under LED white light, the reaction was stirred at room temperature for 3 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 50 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by column chromatography to precipitate a white solid product with an mp of 20-21°C. A sample was analyzed by GC, revealing an 86% conversion rate, no polychlorinated products, and a 95% yield. Figure 6 2,4-dichloroacetophenone 13 CNMR image.

[0089] Example 14 Chlorination of p-chloroacetophenone

[0090] 8.0 mL of potassium chloride, 9.7 mL (166.0 mmol) of acetic acid, 140 mL of 1,4-dioxane, and 11.0 mL (83.0 mmol) of p-chloroacetophenone were added to the photoreactor in sequence. While stirring, 0.015 g of ferric chloride catalyst was added. Under irradiation with a 300 W xenon lamp, the mixture was stirred at room temperature for 6 h. The reaction was monitored by gas chromatography.

[0091] After the reaction mixture was allowed to stand, 50 ml of saturated brine was added. The aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried, and purified by rectification to precipitate a white solid product with an mp of 20-21°C. A sample was taken and analyzed by GC, revealing a conversion of 85%, no polychlorinated products detected, and a yield of 91%.

[0092] Example 15 Chlorination of cyclohexanone

[0093] Take 1.0mL acetonitrile and 3.0mL chlorobenzene, 0.3ml (5.0mol) glacial acetic acid, and 1.0mL (9.0mmol) cyclohexanone and add them to the photoreactor in sequence; while stirring, add 1.08g FeCl3 photocatalyst, and react at room temperature for 6 hours under the irradiation of LED 470nm lamp; track the reaction by gas chromatography; after the reaction solution is allowed to stand, add 50ml saturated brine, extract with ethyl acetate, wash with water and saturated brine, dry the organic phase, and rectify the organic phase to collect the fraction at 80-82℃ / 10mmHg, which is 2-chlorocyclohexanone. Samples were taken and analyzed by GS, and the conversion rate was 91%, no polychlorinated products were detected, and the yield was 89%. Figure 7 GC-MS chart of cyclohexanone-chlorocyclohexanone mixture. Figure 9 Chlorocyclohexanone 13 CNMR image.

[0094] Example 16 Chlorination of cyclohexanone

[0095] Take 1.0mL acetonitrile and 4.0mL fluorobenzene, 0.3ml (5.0mol) glacial acetic acid, and 1.0mL (9.0mmol) cyclohexanone and add them to the photoreactor in sequence; while stirring, add 1.08g FeCl3 photocatalyst, and react at room temperature for 6h under the irradiation of LED 470nm lamp; track the reaction by gas chromatography; after the reaction solution is allowed to stand, add 50ml saturated brine, extract with ethyl acetate, wash with water and saturated brine, dry the organic phase, and rectify the organic phase to collect the fraction at 80-82℃ / 10mmHg, which is 2-chlorocyclohexanone. Samples were taken and analyzed by GS, the conversion rate was 93%, no polychlorinated products were detected, and the yield was 90%. Figure 8 For chlorocyclohexanone 1 HNMR spectrum.

[0096] Example 17 Chlorination of cyclohexanone

[0097] 19.8g of magnesium chloride (0.2mol of chloride ion), 24.0mL (0.4mol) of acetic acid, 20.0mL of acetonitrile, 150.0mL of fluorobenzene, and 10.0mL (90.0mmol) of cyclohexanone were added sequentially to a photoreactor. With stirring, 0.5g of ferric sulfate catalyst was added, and a 300W xenon lamp was turned on. The reaction was allowed to react at room temperature for 4 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 50ml of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and subjected to rectification. The fraction at 80-82°C / 10mmHg was collected, which was 2-chlorocyclohexanone. A sample was taken and analyzed by GC, revealing a conversion of 95%, no polychlorinated products, and a yield of 90%.

[0098] Example 18 Chlorination of cyclohexanone

[0099] 19.8g of magnesium chloride (0.2mol of chloride ion), 24.0mL (0.4mol) of hydrochloric acid, 20.0mL of acetonitrile, 120.0mL of chlorobenzene, and 10.0mL (90.0mmol) of cyclohexanone were added sequentially to a photoreactor. With stirring, 0.5g of ferric chloride and 0,2-dichloroferric chloride catalyst were added. A 300W xenon lamp was turned on and the reaction was allowed to proceed at room temperature for 6 hours. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 50ml of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and subjected to rectification. The fraction at 80-82°C / 10mmHg was collected, which was 2-chlorocyclohexanone. A sample was taken and analyzed by GC, revealing a conversion of 91%, no polychlorinated products, and an 89% yield.

[0100] Example 19 Chlorination of cyclohexanone

[0101] S1: 3.6 g of sodium chloride (0.6 mol of chloride ion), 24.0 mL of hydrochloric acid (0.4 mol), 150 mL of acetonitrile, and 10.0 mL (90 mmol) of cyclohexanone were added sequentially to a photoreactor. With stirring, 0.5 g of iron powder catalyst was added, and a 400 nm LED light source was used. The reaction was allowed to react at room temperature for 8 h. The reaction was monitored by gas chromatography. After the reaction solution was allowed to stand, 50 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and subjected to rectification. The fraction at 80-82°C / 10 mmHg was collected, which was 2-chlorocyclohexanone. A sample was taken and analyzed by GC, revealing an 82% conversion, no polychlorinated products, and an 80% yield.

[0102] Example 20 Chlorination of cyclohexanone

[0103] Take 0.05 mg (1.0 mmol) of magnesium chloride, 0.03 mL (1.0 mmol) of hydrochloric acid, 5.0 mL of acetonitrile, and 0.06 mL (0.5 mmol) of cyclohexanone and add them to the photoreactor in sequence; under stirring, add 0.01 g of iron powder catalyst, turn on the LED 365 nm light source, and react at room temperature for 8 hours; use gas chromatography to track the reaction; after the reaction is completed, let the reaction liquid stand, add 50 ml of saturated brine, extract with ethyl acetate, wash the organic phase with water and saturated brine, dry the organic phase, and purify the dried organic phase by distillation to obtain the corresponding chlorinated product.

[0104] The sample was analyzed by GS, and the conversion rate was 77%, no polychlorinated products were detected, and the yield was 72%.

[0105] Example 21 Chlorination of benzocyclohexanone

[0106] 0.05 mg (1.0 mmol) of magnesium chloride, 0.053 mL (1.0 mmol) of acetic acid, 5.0 mL of acetonitrile, and 0.5 mmol of benzocyclohexanone were added to a photoreactor in this order. With stirring, 0.012 g of ferric nitrate nonahydrate catalyst was added, and the reaction was conducted at room temperature for 4 hours under a 420 nm LED light source. The reaction was monitored by gas chromatography. After completion, the reaction mixture was allowed to stand, 40 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by rectification to obtain the corresponding chlorinated product. A sample was taken and analyzed by GC, revealing a conversion of 95%, no polychlorinated products detected, and a yield of 90%.

[0107] Example 22 Chlorination of cyclohexanone

[0108] 0.042g (1.0mmol) of lithium chloride, 0.058mL (1.0mmol) of acetic acid, 3.0mL of 1,4-dioxane, and 0.06mL (0.5mmol) of cyclohexanone were added sequentially to a photoreactor. With stirring, 0.014g of ferrous chloride catalyst was added, and a 440nm LED light source was used. The reaction was allowed to react at room temperature for 6 hours. The reaction was monitored by gas chromatography. After completion of the reaction, the reaction mixture was allowed to stand, 30ml of saturated brine was added, and extraction with ethyl acetate was performed. The organic phase was washed with water and saturated brine, dried, and purified by rectification to obtain the corresponding chlorinated product. Samples were analyzed by GC, revealing a conversion of 79%, no polychlorinated products were detected, and a yield of 76%.

[0109] Example 23 Chlorination of cyclohexanone

[0110] 0.054 g (1.0 mmol) of ammonium chloride, 0.20 g (1.0 mmol) of p-nitrobenzenesulfonic acid, 1.0 mL of acetonitrile, 3.0 mL of fluorobenzene, and 0.06 mL (0.5 mmol) of cyclohexanone were sequentially added to a photoreactor. With stirring, 0.01 g of iron powder catalyst was added, and a 450 nm LED light source was used. The reaction was allowed to react at room temperature for 5 hours. The reaction was tracked by gas chromatography. After completion of the reaction, the reaction solution was allowed to stand, 30 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by rectification to obtain the corresponding chlorinated product. Samples were analyzed by GC, revealing a conversion of 82%, no polychlorinated products, and an 81% yield.

[0111] Example 24 Chlorination of cyclohexanone

[0112] Take 0.324g (2.0mmol) of magnesium chloride and 0.15g (1.0mmol) of trifluoromethanesulfonic acid, 5.0mL of DMF, and 0.06mL (0.5mmol) of cyclohexanone and add them to the photoreactor in sequence; under stirring, add 0.32g of iron acetate catalyst, turn on the LED white light source, and react at room temperature for 2h; track the reaction by gas chromatography; after the reaction is completed, let the reaction liquid stand, add 30ml of saturated brine, extract with ethyl acetate, wash the organic phase with water and saturated brine, dry the organic phase, and distill and purify the dried organic phase to obtain the corresponding chlorinated product.

[0113] The sample was analyzed by GS, and the conversion rate was 88%, no polychlorinated products were detected, and the yield was 87%.

[0114] Example 25 Chlorination of pyridin[b]cyclopentanone-5

[0115] S1: 0.05 g (1.0 mmol) of magnesium chloride, 3.0 mmol of acetic acid, 2.0 mL of acetonitrile, 0.5 mL of water, and 0.5 mmol of pyridin[b]cyclopentanone-5 were added sequentially to a photoreactor. Under stirring, 0.01 g of ferrous chloride catalyst was added, and the reaction was conducted at room temperature for 7 h under an LED white light source. The reaction was monitored by gas chromatography. After completion of the reaction, the reaction solution was allowed to stand, 30 mL of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by rectification to obtain the corresponding chlorinated product. A sample was taken and analyzed by GC, revealing an 83% conversion rate, no polychlorinated products, and an 82% yield.

[0116] Example 26 Chlorination of pyridin[b]cyclopentanone-7

[0117] 0.051g (1.0mmol) of magnesium chloride, 0.25g (2.0mmol) of benzenesulfonic acid, 5.0mL of acetonitrile, and 0.5mmol of pyridin[b]cyclopentanone-7 were added sequentially to a photoreactor. With stirring, 0.03g of ferric chloride catalyst was added, and the reaction was carried out at room temperature for 4 hours under an LED light source. The reaction was monitored by gas chromatography. After completion of the reaction, the reaction solution was allowed to stand, 30ml of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by rectification to obtain the corresponding chlorinated product. Samples were analyzed by GC, revealing an 81% conversion rate, no polychlorinated products, and an 80% yield.

[0118] Example 27 Chlorination of cyclohexanone

[0119] 0.05g (1.0mmol) of magnesium chloride, 0.15mL (2.0mmol) of trifluoroacetic acid, 5.0mL of acetonitrile, and 0.07mL (0.6mmol) of cyclohexanone were added sequentially to a photoreactor. With stirring, 0.015g of an iron catalyst was added, and the reaction was conducted at room temperature for 2 hours under an LED light source. The reaction was monitored by gas chromatography. After completion of the reaction, the reaction solution was allowed to stand, 30ml of saturated brine was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried, and purified by rectification to obtain the corresponding chlorinated product. Samples were analyzed by GC, revealing an 83% conversion rate, no polychlorinated products, and an 80% yield.

[0120] Example 28 Chlorination of Pinacolone

[0121] Take 0.05g (1.0mmol) of magnesium chloride and 0.15mL (2.0mmol) of acetic acid, 5.0mL of fluorobenzene, and 0.6mmol of pinacol, and add them to the photoreactor in sequence; under stirring, add 0.015g of iron catalyst, turn on the LED light source, and react at room temperature for 3h; use gas chromatography to track the reaction; after the reaction is completed, let the reaction liquid stand, add 30ml of saturated brine, extract with ethyl acetate, wash the organic phase with water and saturated brine, dry the organic phase, and purify the dried organic phase by distillation to obtain the corresponding chlorinated product. Samples were analyzed by GS, and the conversion rate was 88%, no polychlorinated products were detected, and the yield was 85%. Figure 10 is the GC-MS chart of pinacolone-chloropinacolone, Figure 11 is the 1HNMR diagram of chloropinacolone, Figure 12 This is the 13CNMR diagram of chloropinacolone.

[0122] Because iron catalysts have similar physical and chemical properties, they have strong absorption efficiency for visible light, including sunlight and LED lights, and can generate halogen radicals from halide ions X-, initiating halogenation reactions. Therefore, this list of other nanometal / semiconductor composite photocatalysts that can photocatalyze the halogenation of cycloalkanes is not exhaustive.

[0123] The beneficial effects that can be achieved by the present invention are as follows:

[0124] 1. This invention utilizes inexpensive iron as a photocatalyst and an inorganic salt as a chlorine source in a heterogeneous system to directly achieve monochlorination of various carbonyl C-H bonds under irradiation with visible light, sunlight, or LED light. This development represents a novel, environmentally friendly, highly selective, and energy-efficient green pathway for the synthesis of monochlorides.

[0125] 2. The present invention addresses the drawbacks of the conventional method of synthesizing organic chlorides using toxic chlorine gas under illumination. Instead, it uses a non-toxic inorganic salt as a chlorine source and iron as a photocatalyst to selectively chlorinate different types of CH at room temperature, atmospheric pressure, and illumination. Therefore, the present invention provides a new chlorination method that is energy-saving, environmentally friendly, and low-cost.

[0126] 3. The method of the present invention can be implemented at room temperature and normal pressure. The substitution reaction is carried out under heterogeneous conditions. The substitution reaction does not require heating and can be carried out at room temperature only under visible light irradiation (including sunlight).

[0127] 4. method of the present invention, resulting chloroproduct, mainly is the product of single chloro, and the selectivity of single chlorine replacement is higher than 95%.Therefore, the present invention has low cost, and equipment is simple and easy to operate, and product selectivity is high, easily separates, and can be the advantage of large-scale production, is a kind of novel, environmentally friendly, highly selective, low-energy-consumption organic halogenation brand-new, feasible green approach, has potential industrial application value.

[0128] Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

Claims

1. A method for the chlorination of carbonyl compounds α-H by iron catalysis, characterized in that: The chlorination process is shown below: The carbonyl compound containing α-H is selected from the following group: R 1 or R 2 It is any one of H, alkyl aromatic hydrocarbon group, heterocyclic hydrocarbon group, aliphatic hydrocarbon group and alicyclic group.

2. The method for chlorinating an iron-catalyzed carbonyl compound α-H according to claim 1, characterized in that: The steps include: S1: placing an inorganic salt chloride and an inorganic acid or organic acid as a chlorine source, an organic solvent and an α-H-containing carbonyl compound in a photoreactor; S2: While stirring, under sunlight or 300W xenon lamp or LED light, add iron catalyst in batches to catalyze the reaction. After the reaction period, stop stirring; S3: After the reaction solution is allowed to stand, the organic phase is washed and dried, and the dried organic phase is subjected to rectification or recrystallization separation, or chromatography purification to obtain the corresponding organic halogenated product.

3. The method for chlorinating an iron-catalyzed carbonyl compound α-H according to claim 2, wherein: In step S1, the inorganic salt chloride serving as a chlorine source is any one of magnesium chloride, sodium chloride, potassium chloride, calcium chloride, lithium chloride, ammonium chloride, and ferric chloride.

4. The method for chlorinating an iron-catalyzed carbonyl compound α-H according to claim 2, wherein: In step S1, the carbonyl compound containing α-H is a ketone or an aldehyde; wherein the ketone or aldehyde containing α-H is selected from aliphatic ketones, alicyclic ketones, alkyl aryl ketones, aliphatic aldehydes or alicyclic aldehydes; Among them, aliphatic ketones include methyl ketones; Among them, the alicyclic ketones are cyclopentanone, cyclohexanone, cycloheptanone or their benzo derivatives, aromatic heterocyclic alicyclic ketones and aliphatic condensed ring derivatives, the above alicyclic ketones also include but are not limited to camphor ketone, anisone and macrocyclic ketones, macrocyclic ketones include but are not limited to musk ketone; Wherein, the alkyl aryl ketone is acetophenone, aromatic heterocyclic ethyl ketone, propiophenone, aromatic heterocyclic ethyl ketone series compounds or aromatic ring substituted derivatives, which include but are not limited to halogenated aryl, alkoxyaryl, nitroaryl, aminoaryl, sulfonylaryl, tertiary alkyl aryl; The halogenated aryl group includes fluoro, chloro, bromo or iodo.

5. The method for chlorinating carbonyl compounds α-H by iron catalysis according to claim 2, characterized in that: In step S1, the inorganic acid used is any one of hydrochloric acid, sulfuric acid, phosphoric acid or sulfonic acid; the organic acid used is any one of acetic acid, benzoic acid, chloroacetic acid, trichloroacetic acid and trifluoroacetic acid.

6. The method for chlorinating carbonyl compounds α-H by iron catalysis according to claim 5, characterized in that: The sulfonic acid is selected from any one of methanesulfonic acid, trifluoromethanesulfonic acid, chlorosulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, nitrobenzenesulfonic acid or benzene disulfonic acid.

7. The method for chlorinating carbonyl compounds α-H by iron catalysis according to claim 2, characterized in that: In step S1, the iron catalyst used is selected from any one of iron powder, ferric chloride, ferrous chloride, ferric sulfate, ferrous sulfate, ferric nitrate, ferrosoferric oxide, ferric oxide, and iron salt hydrate.

8. The method for chlorinating carbonyl compounds α-H by iron catalysis according to claim 2, characterized in that: In step S1, the organic solvent is selected from one or any two of acetonitrile, acetonitrile aqueous solution, DMF, chlorobenzene, fluorobenzene, 1,4-dioxane or 1,2-dichloroethane.

9. The method for chlorinating carbonyl compounds α-H by iron catalysis according to claim 2, characterized in that: In step S1, the molar ratio of the added inorganic chloride ion to the reaction substrate is between 0.5:1 and 28:

1.

10. The method for chlorinating carbonyl compounds α-H by iron catalysis according to claim 2, characterized in that: In step S1, the molar ratio of the added organic acid or inorganic acid to the chloride ion in the inorganic chloride salt is between 1:1 and 1:10; in the reaction, the molar ratio of the amount of the iron catalyst used to the α-H-containing carbonyl compound is between 1.0 and 40%.

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