Iron-visible light co-catalysis carbon-carbon repeat bond addition chlorination method
Through the iron-visible light cocatalytic method, inorganic salt chloride is used as the chlorine source, and under the presence of iron powder or iron salt under visible light, the problems of low selectivity and high energy consumption of carbon-carbon repeated bond addition in the prior art are solved, and a high selectivity and low energy consumption of carbon-carbon repeated bond addition chlorination reaction is achieved.
Patent Information
- Application Number
- CN202410011670.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-01-04
- Publication Date
- 2025-07-04
AI Technical Summary
The existing carbon-carbon repeated bond addition chlorination methods have low selectivity, high energy consumption, and the use of chlorine gas has safety and contamination problems.
The iron-visible light cocatalytic method is used to use the inorganic salt chloride as the chlorine source, and the carbon-carbon repeated bond addition chlorination of olefins or alkynes under visible light radiation is achieved.
It realizes carbon-carbon repeated bond addition chlorination with high selectivity and low energy consumption, and prepares dihalide products, which is environmentally friendly and practical.
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Figure CN120247644A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to a chlorination method, and in particular to a method for addition chlorination of carbon-carbon multiple bonds, belonging to the technical field of organic chemistry. Background Art
[0002] Chlorination is one of the common main reactions in organic synthesis and fine chemical production. In the prior art, there are methods of chlorination with chlorine using hydrocarbons as basic raw materials, methods of addition with chlorine as the chlorine source to unsaturated systems, or co-catalysis of visible light with catalysts based on precious metals or non-ferrous metals for the addition of chlorine derivatives to alkenes. Although these technologies are relatively mature, the light corrosiveness, high hazard, and high pollution of chlorine make their inherent safety poor and do not conform to the basic principles of green chemistry.
[0003] In addition, during the process of halogen addition reaction on the double bond of alkenes or derivatives of alkenes, it often causes the halogen to simultaneously replace the hydrogen atoms on other carbons, resulting in a large variety of products, low purity of the target product, and great difficulty in separation and purification. Therefore, a new type, environmentally friendly, highly selective, and low-energy-consuming addition chlorination reaction method for multiple bonds is the goal pursued by chemical engineering. The present invention uses readily available and inexpensive iron as a visible light catalyst, and under the conditions of light radiation and in the absence of strong oxidants, uses inorganic chloride as the chlorine source to achieve addition chlorination of multiple bonds with high conversion and high selectivity, and is used to synthesize corresponding chlorides from alkenes or alkynes as raw materials. This method has not been reported yet. Summary of the Invention
[0004] In view of the above problems, the present invention provides an iron-visible light co-catalyzed method for addition chlorination of carbon-carbon multiple bonds to solve the technical problems of low selectivity and high energy consumption during the existing addition chlorination of carbon-carbon multiple bonds.
[0005] To achieve the above object, the technical solution of an iron-visible light co-catalyzed method for addition chlorination of carbon-carbon multiple bonds of the present invention is as follows: This method uses an alkene as a reaction substrate and an inorganic chloride as the chlorine source. Under the conditions of the absence of strong oxidants and the presence of iron powder or iron salt, through visible light radiation, selective addition of carbon-carbon multiple bonds in the reaction substrate is achieved to prepare a dihalide product, and its reaction general formula is:
[0006]
[0007] In the reaction general formula, the structures of R and Y are not limited; n is 1, 2, or 3; M is a cation, including metal ions and ammonium ions.
[0008] Further, the cation is any one of sodium, potassium, magnesium, calcium, lithium, iron, copper, and ammonium ions.
[0009] Further, the method includes the following steps:
[0010] S1 Place the inorganic salt chloride MCln as the chlorine source, an acid, iron or an iron salt, and the reaction substrate in a photoreactor containing an organic solvent;
[0011] S2 Under stirring, catalyze the reaction under illumination with LED light or 300W xenon light. After the reaction for a period of time, stop stirring;
[0012] S3 After the reaction solution is allowed to stand, filter, wash, and dry the organic phase. The dried organic phase is fractionated to recover the solvent, and the residue is subjected to vacuum distillation to obtain the corresponding carbon-carbon multiple bond addition product.
[0013] Further, in step S1, the inorganic salt chloride as the chlorine source is any one of magnesium chloride, sodium chloride, potassium chloride, calcium chloride, lithium chloride, ammonium chloride, iron chloride, and quaternary ammonium chloride; the acid is any one of acetic acid, benzoic acid, chloroacetic acid, trichloroacetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, chlorosulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, nitrobenzenesulfonic acid, or benzenedisulfonic acid.
[0014] Further, the iron or iron salt in step S1 is selected from one or two of iron powder, iron chloride, ferrous chloride, iron acetate, iron sulfate, ferrous sulfate, iron nitrate, magnetite, and iron oxide.
[0015] Further, the reaction substrate includes an alkene or an alkyne;
[0016] Among them, the alkene includes an olefin and a substituted olefin, and is selected from any one of aliphatic olefins, cycloaliphatic olefins, and aryl olefins; the aryl olefin is a benzocycloolefin or a benzheterocyclic compound;
[0017] Among them, the alkyne includes an alkyne and a substituted alkyne, and is selected from any one of aliphatic alkynes and aryl alkynes;
[0018] Among them, R and Y can be hydrogen, alkyl, aryl, carboxyl, alkoxy, halogen, or acyl, and the two are independent of each other.
[0019] Further, the organic solvent in step S1 is any one of acetonitrile, dichloromethane, chloroform, fluorobenzene, methyl tert-butyl ether, tetrahydrofuran, dimethylformamide, and dimethylacetamide.
[0020] Further, the reaction time in step S2 is 6 - 14 hours.
[0021] Further, the molar ratio of chloride ions in the added inorganic salt chloride to the reaction substrate is between 1.5:1 and 28:1.
[0022] Further, the molar ratio of the added acid to the chloride ions in the inorganic salt chloride is between 1:1 and 1:10; the mass ratio of the amount of the used iron or iron salt to the reaction substrate is between 1.0 - 30%.
[0023] The beneficial effects of an iron-visible light co-catalyzed addition chlorination method of carbon-carbon multiple bonds according to the present invention are as follows:
[0024] The present invention provides a chlorination method for selectively adding an inorganic salt chloride as a chlorine source at room temperature by using iron or an iron salt as a visible light catalyst and providing reaction energy with visible light or LED light, and catalyzing the selective addition of a carbon-carbon multiple bond of an alkene or alkyne to prepare a dichloride.
[0025] The method of the present invention directly realizes the selective addition chlorination of an alkene or alkyne multiple bond by using chloride ions instead of chlorine gas, which has great theoretical significance and practical value.
[0026] The addition of the multiple bond in the alkene or alkyne of the present invention and the inorganic salt chloride under the co-catalysis of iron or its salt and visible light can be carried out at room temperature and normal pressure, with low cost, simple equipment and easy operation. It is a new, environmentally friendly, highly selective and low-energy consumption green synthesis route for organic chlorides, and has important potential applications in industrial production. Description of the Drawings
[0027] The present invention will be further described in detail below with reference to the drawings and specific embodiments.
[0028] Figure 1 It is the 1 HNMR spectrum of the chloroaddition product 1,2-dichlorocyclohexane of cyclohexene;
[0029] Figure 2 It is the 1 HNMR spectrum of the chloroaddition product (1,2-dichloroethyl)benzene of styrene;
[0030] Figure 3 It is the 1 HNMR spectrum of the chloroaddition product benzodichlorocyclopentane of benzocyclopentene (indene);
[0031] Figure 4 It is the 1 HNMR spectrum of the chloroaddition product of N-Boc-tryptophan methyl ester. Detailed Embodiments
[0032] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention. Many specific details are set forth in the following description in order to fully understand the present invention, but the present invention may also be implemented in other ways different from those described herein. Those skilled in the art can make similar extensions without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.
[0033] The technical solution of an iron-visible light co-catalyzed addition chlorination method of carbon-carbon multiple bonds is as follows: This method uses olefins as reaction substrates and inorganic chlorides as chlorine sources. In the absence of strong oxidants and in the presence of iron powder or iron salts, selective addition of carbon-carbon multiple bonds in the reaction substrates is achieved through visible light irradiation to prepare dihalogenated products. The reaction general formula is:
[0034]
[0035] In the reaction general formula, the structures of R and Y are not limited; n is 1, 2, or 3; M is a cation, including metal ions and ammonium ions.
[0036] Further, the cation is any one of sodium, potassium, magnesium, calcium, lithium, iron, copper, and ammonium ions.
[0037] The method includes the following steps:
[0038] S1 Place the inorganic salt chloride MCln as the chlorine source, an acid, iron or an iron salt, and the reaction substrate in a photoreactor containing an organic solvent;
[0039] The inorganic salt chloride as the chlorine source is any one of magnesium chloride, sodium chloride, potassium chloride, calcium chloride, lithium chloride, ammonium chloride, iron chloride, and quaternary ammonium chloride; the acid is any one of acetic acid, benzoic acid, chloroacetic acid, trichloroacetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, chlorosulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, nitrobenzenesulfonic acid, or benzenedisulfonic acid;
[0040] The iron or iron salt is selected from one or two of iron powder, iron chloride, ferrous chloride, iron acetate, iron sulfate, ferrous sulfate, iron nitrate, magnetite, and iron oxide;
[0041] The reaction substrate includes an alkene or an alkyne;
[0042] Among them, the alkene includes olefins and substituted olefins, and is selected from any one of aliphatic olefins, alicyclic olefins, and aryl olefins; the aryl olefin is a benzocyclic olefin or a benzheterocyclic compound;
[0043] Among them, the alkyne includes alkynes and substituted alkynes, and is selected from any one of aliphatic alkynes and aryl alkynes;
[0044] Among them, R and Y can be hydrogen, alkyl, aryl, carboxyl, alkoxy, halogen, or acyl, and the two are independent of each other;
[0045] The organic solvent is any one of acetonitrile, dichloromethane, chloroform, fluorobenzene, methyl tert-butyl ether, tetrahydrofuran, dimethylformamide, and dimethylacetamide;
[0046] Under stirring, the catalytic reaction is carried out under the irradiation of LED light or 300W xenon light. After the reaction for a period of time, the stirring is stopped; preferably, the reaction time is 6 - 14 hours
[0047] After the reaction solution is allowed to stand, it is filtered, the organic phase is washed and dried. The dried organic phase is fractionated to recover the solvent, and the residue is subjected to vacuum distillation to obtain the corresponding carbon-carbon multiple bond addition product.
[0048] The molar ratio of chloride ions in the inorganic salt chloride added in the above method to the reaction substrate is between 1.5:1 - 28:1; the molar ratio of the acid added to the chloride ions in the inorganic salt chloride is between 1:1 - 1:10; the dosage of iron or iron salt used is between 1.0 - 30% of the mass of the reaction substrate.
[0049] Example 1: Addition chlorination of cyclohexene
[0050] 3.5 g of sodium chloride, 5 ml of glacial acetic acid, and 50 ml of acetonitrile are placed in a photoreactor, and then 0.45 g of ferric chloride and 15 ml of cyclohexene (reaction substrate) are added. The LED lamp is turned on for irradiation, and the reaction is stirred at room temperature for 9 h, and then the stirring is stopped; the catalyst is recovered by filtration, and acetonitrile is recovered by vacuum concentration. Water and methyl tert-butyl ether are added to the residue, and the aqueous phase is extracted 3 times with methyl tert-butyl ether. The organic phases are combined, washed with saturated brine, dried, and the dried organic phase is separated and concentrated under reduced pressure. The residue is subjected to vacuum distillation, and the fraction at 96 - 99 °C / 10 mmHg is collected, which is 1,2-dichlorocyclohexane with a yield of 83%; as Figure 1 shown in the 1 HNMR spectrum of the cyclohexene chloroaddition product 1,2-dichlorocyclohexane.
[0051]
[0052] Example 2: Addition chlorination of cyclohexene
[0053] The same procedure as in Example 1 is used, with magnesium chloride replacing sodium chloride and 1.5 mL of trifluoromethylsulfonic acid replacing acetic acid, and the reaction time is controlled at 6 h. The yield of 1,2-dichlorocyclohexane is 86%.
[0054]
[0055] Example 3: Addition chlorination of cyclohexene
[0056] The same procedure as in Example 1 is used, with 1.5 mL of trifluoromethylsulfonic acid replacing acetic acid, fluorobenzene replacing acetonitrile, and iron powder replacing ferric chloride, and the reaction time is controlled at 8 h. The yield of 1,2-dichlorocyclohexane is 78%.
[0057] Example 4: Addition chlorination of cyclohexene
[0058] The same procedure as in Example 1 was used, with equimolar tetrabutylammonium chloride replacing sodium chloride, 1.5 mL of methanesulfonic acid replacing acetic acid, equimolar iron sulfate replacing ferric chloride, and methyl tert-butyl ether replacing the solvent acetonitrile. The reaction time was controlled at 8 h. The yield of 1,2-dichlorocyclohexane was 84%.
[0059]
[0060] Example 5: Addition Chlorination of Propylene
[0061] The same procedure as in Example 1 was used, with the substrate replaced by a solution of propylene in dichloromethane instead of cyclohexene and the solvent acetonitrile.
[0062] After treatment of the reaction solution, the fraction of 1,2-dichloropropane with a boiling point of 94 - 96 °C was collected by distillation, and the yield was 89%.
[0063]
[0064] Example 6: Addition Chlorination of Styrene
[0065] 0.8 mol of calcium chloride, 2.8 mL of chlorosulfonic acid, and 50 mL of acetonitrile were placed in a photoreactor, and then 0.08 mol of ferric chloride and 10 mL of styrene (the reaction substrate) were added. The xenon lamp was turned on for irradiation, and the reaction was stirred at room temperature for 8 h, then the stirring was stopped; the catalyst was recovered by filtration, and acetonitrile was recovered by concentration under reduced pressure. Water and methyl tert-butyl ether were added to the residue, and the aqueous phase was extracted 3 times with methyl tert-butyl ether. The organic phases were combined, washed with saturated brine, dried, and the dried organic phase was separated and concentrated under reduced pressure. The residue was rectified under reduced pressure to obtain (1,2-dichloroethyl)benzene with a boiling point of 105 - 108 °C / 5 mmHg and a yield of 88%. As Figure 2 shown in the 1 HNMR spectrum of the styrene chlorination product (1,2-dichloroethyl)benzene.
[0066]
[0067] Example 7: Addition Chlorination of Styrene
[0068] The same procedure as in Example 6 was used, with 5 mL of trichloroacetic acid replacing chlorosulfonic acid and 60 mL of a mixed solvent of acetonitrile / water (10:1) replacing acetonitrile to obtain a mixture of 5:2 dichlorination addition product and chlorohydroxylation product.
[0069]
[0070] Example 8: Addition Chlorination of Phenylacetylene
[0071] Place 0.8 mol of magnesium chloride, 2.8 ml of chlorosulfonic acid, and 60 ml of acetonitrile in a photoreactor, and then add 0.13 mol of ferrous chloride and 12 ml of phenylacetylene (reaction substrate). Turn on the xenon lamp for irradiation, stir the reaction at room temperature for 10 h, and stop stirring; filter to recover the catalyst and concentrate under reduced pressure to recover acetonitrile. Add water and methyl tert-butyl ether to the residue, and extract the aqueous phase 3 times with methyl tert-butyl ether. Combine the organic phases, wash with saturated brine, dry the organic phase, and separate and concentrate the dried organic phase under reduced pressure. The residue is subjected to vacuum distillation to obtain (1,2-dichloroethenyl)benzene, boiling point 116 - 118 °C / 6 mmHg, with a yield of 76%.
[0072]
[0073] Example 9: Addition chlorination of 1-octyne
[0074] Using the same procedure as in Example 7, replace phenylacetylene with 1-octyne and ferrous chloride with an equimolar amount of ferric sulfate. The reaction product is separated by column chromatography to obtain 1,2-dichloro-1-octene with a yield of 77%.
[0075]
[0076] Example 10: Addition chlorination of indene
[0077] Under stirring conditions, add 2 mL (20 mmol) of indene, 1.5 g of p-toluenesulfonic acid, and 1.6 g (10 mmol) of ferric chloride successively to a quartz photoreactor containing 40 mL of acetonitrile and 80 mmol of magnesium chloride. Turn on the LED lamp for irradiation and stir the reaction at room temperature for 10 h. After the reaction is completed, filter with suction to collect the reaction solution, concentrate under reduced pressure, and recover the solvent. Dilute the residue with saturated NaCl solution and extract 3 times with ethyl acetate. Wash the organic phase with saturated NaHCO3 solution and saturated NaCl solution respectively, and dry with anhydrous Na2SO4. Concentrate to recover ethyl acetate, and separate the residue by silica gel column chromatography using a 10:1 mixture of ethyl acetate and petroleum ether as the eluent to obtain the carbon-carbon double bond chlorination product with a yield of 76%. As Figure 3 shown, the chlorination product of benzocyclopentene (indene) is benzodichlorocyclopentane 1 HNMR spectrum.
[0078]
[0079] Example 11: Addition chlorination of N-Boc-indole
[0080] Under stirring conditions, 20 mmol of N-Boc-indole, 3.5 mL of acetic acid, and 80 mmol of magnesium chloride were successively added to a quartz photoreactor containing 35 mL of acetonitrile and 1.6 g (10 mmol) of iron(III) chloride. The xenon lamp was turned on for irradiation, and the reaction was stirred at room temperature for 8.5 h. After the reaction was completed, the reaction solution was collected by suction filtration, concentrated under reduced pressure, and the solvent was recovered. The residue was diluted with saturated NaCl solution and extracted with ethyl acetate three times. The organic phase was washed with saturated NaHCO3 solution and saturated NaCl solution respectively, and dried over anhydrous Na2SO4. Ethyl acetate was concentrated and recovered, and the residue was separated by silica gel column chromatography using a 10:1 mixture of ethyl acetate and petroleum ether as the eluent to obtain the carbon-carbon double bond chlorine addition product with a yield of 78%.
[0081]
[0082] Example 12 Addition Chlorination of Benzofuran
[0083] Using the same procedure as in Example 11, benzofuran was used instead of N-Boc-indole. The residue after concentration of the ethyl acetate extract was separated by silica gel column chromatography using a 3:2 mixture of n-hexane / ethyl acetate as the eluent to obtain the carbon-carbon double bond chlorine addition product with a yield of 75%.
[0084]
[0085] Example 13 Addition Chlorination of N-Boc-L-tryptophan Methyl Ester
[0086] Using the same procedure as in Example 11, N-Boc-L-tryptophan methyl ester was used instead of N-Boc-indole. The residue after concentration of the ethyl acetate extract was separated by silica gel column chromatography using a 1:1 mixture of n-hexane / ethyl acetate as the eluent to obtain the carbon-carbon double bond chlorine addition product with a yield of 68%. As Figure 4 shown in the N-Boc-tryptophan methyl ester chlorine addition product 1 1H NMR spectrum.
[0087]
[0088] Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of them. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the scope of protection of the present invention.
Claims
1. A method for iron-visible light co-catalyzed addition chlorination of carbon-carbon multiple bonds, characterized in that, This method uses olefins as reaction substrates and inorganic chlorides as chlorine sources. In the absence of strong oxidants and in the presence of iron powder or iron salts, under visible light irradiation, selective addition of carbon-carbon multiple bonds in the reaction substrates is achieved to prepare dihalogenated products, and its reaction general formula is: In the reaction general formula, the structures of R and Y are not limited; n is 1, 2, or 3; M is a cation, including metal ions and ammonium ions.
2. The method for iron-visible light co-catalyzed addition chlorination of carbon-carbon multiple bonds according to claim 1, wherein The cation is any one of sodium, potassium, magnesium, calcium, lithium, iron, copper, and ammonium ions.
3. A method for iron-visible light co-catalyzed addition chlorination of carbon-carbon multiple bonds according to claim 1 or 2, characterized in that, The method includes the following steps: S1 Place the inorganic salt chloride MCln as the chlorine source, an acid, iron or an iron salt, and the reaction substrate in a photoreactor containing an organic solvent. S2 Under stirring, catalyze the reaction under irradiation with LED light or 300W xenon light. After reacting for a period of time, stop stirring. S3 After the reaction solution stands still, filter, wash, and dry the organic phase. The dried organic phase is fractionated to recover the solvent, and the residue is subjected to vacuum distillation to obtain the corresponding carbon-carbon multiple bond addition product.
4. A method for iron-visible light co-catalyzed addition chlorination of carbon-carbon multiple bonds according to claim 3, characterized in that In step S1, the inorganic salt chloride as the chlorine source is any one of magnesium chloride, sodium chloride, potassium chloride, calcium chloride, lithium chloride, ammonium chloride, iron chloride, and quaternary ammonium chloride; the acid is any one of acetic acid, benzoic acid, chloroacetic acid, trichloroacetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, chlorosulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, nitrobenzenesulfonic acid, or benzenedisulfonic acid.
5. A method for iron-visible light co-catalyzed addition chlorination of carbon-carbon multiple bonds according to claim 1, characterized in that, The iron or iron salt in step S1 is selected from one or two of iron powder, iron chloride, ferrous chloride, iron acetate, iron sulfate, ferrous sulfate, iron nitrate, magnetite, and iron oxide.
6. A method for the addition chlorination of carbon-carbon multiple bonds by iron-visible light co-catalysis according to claim 1, characterized in that, The reaction substrate includes alkenes or alkynes; Among them, alkenes include olefins and substituted olefins, and are selected from any one of aliphatic alkenes, cycloaliphatic alkenes, and aryl alkenes; the aryl alkene is a benzocycloalkene or a benzheterocyclic compound; Among them, alkynes include alkynes and substituted alkynes, and are selected from any one of aliphatic alkynes and aryl alkynes; Among them, R and Y can be hydrogen, alkyl, aryl, carboxyl, alkoxy, halogen, or acyl, and the two are independent of each other.
7. A method for iron-visible light co-catalyzed addition chlorination of carbon-carbon multiple bonds according to claim 1, characterized in that, The organic solvent in step S1 is any one of acetonitrile, dichloromethane, chloroform, fluorobenzene, methyl tert-butyl ether, tetrahydrofuran, dimethylformamide, and dimethylacetamide.
8. A method for iron-visible light co-catalyzed addition chlorination of carbon-carbon multiple bonds according to claim 1, characterized in that, The reaction time in step S2 is 6 - 14 hours.
9. A method for iron-visible light co-catalyzed addition chlorination of carbon-carbon multiple bonds according to claim 1, characterized in that, The molar ratio of chloride ions in the added inorganic salt chloride to the reaction substrate is between 1.5:1 and 28:
1.
10. A method for iron-visible light co-catalyzed addition chlorination of carbon-carbon multiple bonds according to claim 1, characterized in that, The molar ratio of the added acid to chloride ions in the inorganic salt chloride is between 1:1 and 1:10; The dosage of the used iron or iron salt and the mass ratio of the reaction substrate is between 1.0 - 30%.