CN109400464B - Preparation method of 5-bromolevulinic acid - Google Patents
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Abstract
A preparation method of 5-bromolevulinic acid, belonging to the field of chemical preparation. The preparation method of the 5-bromolevulinic acid comprises the following steps: dissolving 5-bromo-4-pentynoic acid in a solvent, adding water, a copper (II) salt and a ligand, reacting for 4-6 h at 25-90 ℃, and separating to obtain 5-bromolevulinic acid; the ligand is selected from at least one of 1, 10-phenanthroline or derivatives thereof. The preparation method of 5-bromolevulinic acid provided by the invention does not generate a byproduct, namely 3-bromolevulinic acid, and has the advantages of high utilization rate of raw materials, easy separation of products and high yield.
Description
Technical Field
The invention relates to the field of chemical preparation, and in particular relates to a preparation method of 5-bromolevulinic acid.
Background
5-bromolevulinic acid is an important alpha-halogenated ketone compound which can be used as a raw material for preparing 5-aminolevulinic acid, ranolactone, 4, 5-dihydropyridazinone derivatives and other products, wherein, the 4, 5-dihydropyridazinone derivative has the function of expanding blood vessels, the ranunculide can be used for treating tuberculosis, the 5-aminolevulinic acid can be used for treating various skin diseases, acne, upper digestive tract cancer, breast cancer, condyloma acuminatum, rheumatoid arthritis, nevus flammeus, age-related macular degeneration and other diseases, in addition, in the agricultural field, the 5-aminolevulinic acid can be used as pesticide and plant growth regulator, the method can promote photosynthesis, improve photosynthesis efficiency, promote chlorophyll preparation, and increase chlorophyll stability. Since 5-bromolevulinic acid can be used for preparing various important bioactive substances, especially 5-aminolevulinic acid with wide application, the development of a novel method for efficiently preparing 5-bromolevulinic acid is of great significance.
Currently, the main preparation method of 5-bromolevulinic acid and carboxylic ester thereof (such as methyl 5-bromolevulinate, ethyl 5-bromolevulinate, butyl 5-bromolevulinate and the like) is to utilize bromine or NBS (N-bromosuccinimide) to perform bromination reaction on levulinic acid and derivatives thereof, but the method generates more by-products of 3-bromolevulinate substances, so that the yield of 5-bromolevulinate or ester thereof is low.
In addition, the literature reports that the yield of the method for preparing 5-bromolevulinate by bromination of methyl (or ethyl) 5-trimethylsilyl levulinate is up to 90%, but the raw material preparation uses explosive diazomethane substances and is not suitable for industrial production. Research reports on the preparation of alpha-halomethyl ketones from haloalkynes are also numerous, with gold-containing catalysts having good results, e.g. Ph3PAuNTf2(Org.Biomol.Chem.，2012，10：3168)、XPhosAuNTf2[J.Org.Chem.，2013，78(18)：9190]、Ph3PAuCl/AgSbF3(J.org.chem.2014, 79: 2453) and AuCl3/AgNTf2[Eur.J.Org.Chem.，2017，2017(4)：781]The method can be used for preparing alpha-halogenated methyl ketone by catalysis, wherein the hydration reaction yield of the end-position halide of the alkyl alkyne is generally 42-92%, but the preparation methods need expensive gold-containing catalysts, have high production cost and are not suitable for large-scale industrial production.
FeCl in addition to gold3·6H2O、Ce(SO4)2Or in (OTf)3[ chemical journal of higher school, 2014, 35 (12): 2563; chen, 2016, 34 (12): 1251; tetrahedron, 2016, 72, 3818]The catalyst can also be used for catalyzing the hydration reaction of halogenated alkyne respectively to generate alpha-halogenated methyl ketone substances, the yield of the terminal halogenated alkyl alkyne can reach 59-93%, and in addition, tetrafluoroboric acid or AgF/TFA is only suitable for converting aryl alkyne halides into the alpha-halogenated methyl ketone.
In summary, although alkyl-haloalkynes can be converted to α -halomethyl ketones as described above, no method has been found for preparing 5-bromolevulinic acid from 5-bromo-4-pentynoic acid.
Disclosure of Invention
The invention aims to provide a preparation method of 5-bromolevulinic acid, which has the advantages of high utilization rate of raw materials, few byproducts, easy separation of products and high yield.
The technical problem to be solved by the invention is realized by adopting the following technical scheme.
A preparation method of 5-bromolevulinic acid comprises the following steps: dissolving 5-bromo-4-pentynoic acid in a solvent, adding water, a copper (II) salt and a ligand, reacting for 4-6 h at 25-90 ℃, and separating to obtain 5-bromolevulinic acid;
wherein the ligand is selected from at least one of 1, 10-phenanthroline or derivatives thereof.
Further, in a preferred embodiment of the present invention, the solvent is selected from any one of trifluoroacetic acid, acetonitrile, acetic acid, dichloroethane and toluene, or a mixture of trifluoroacetic acid and any one of acetonitrile, acetic acid, dichloroethane and toluene.
Further, in a preferred embodiment of the present invention, when the solvent is composed of two raw materials, the volume ratio of the two raw materials is 1 to 9: 3
Further, in a preferred embodiment of the present invention, the solvent is a mixture of trifluoroacetic acid and dichloroethane.
Further, in a preferred embodiment of the present invention, the copper (II) salt is at least one selected from the group consisting of copper acetate monohydrate, copper trifluoroacetate, copper sulfate, copper chloride and copper bromide.
Further, in a preferred embodiment of the present invention, the ligand is at least one selected from the group consisting of 1, 10-phenanthroline, 2, 9-dimethyl-1, 10-phenanthroline, and 3, 4, 7, 8-tetramethyl-1, 10-phenanthroline.
Further, in a preferred embodiment of the present invention, the above-mentioned 5-bromo-4-pentynoic acid and copper (II) salt are present in a mass ratio of 1:0.01 to 0.2.
Further, in a preferred embodiment of the present invention, the above-mentioned 5-bromo-4-pentynoic acid and ligand are present in a mass ratio of 1:0.01 to 0.2.
Further, in a preferred embodiment of the present invention, the reaction is carried out at 75-85 ℃ for 4-5 hours.
Further, in a preferred embodiment of the present invention, the above separation is performed by column chromatography or recrystallization.
The preparation method of the 5-bromolevulinic acid provided by the embodiment of the invention has the beneficial effects that: the preparation method of the 5-bromolevulinic acid provided by the embodiment of the invention comprises the following steps: dissolving 5-bromo-4-pentynoic acid in a solvent, adding water, a copper (II) salt and a ligand, reacting for 4-6 h at 25-90 ℃, and separating to obtain 5-bromolevulinic acid; the ligand is selected from at least one of 1, 10-phenanthroline or derivatives thereof. The preparation method of 5-bromolevulinic acid provided by the invention does not produce 3-bromolevulinic acid as a byproduct, and has the advantages of high utilization rate of raw materials, easy separation of products and high yield.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1 shows the preparation of 5-bromolevulinic acid according to an embodiment of the invention1H-NMR spectrum;
FIG. 2 shows the preparation of 5-bromolevulinic acid according to the invention13A C-NMR spectrum;
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The following is a specific description of the preparation method of 5-bromolevulinic acid provided in the embodiment of the invention.
A preparation method of 5-bromolevulinic acid comprises the following steps: dissolving 5-bromo-4-pentynoic acid in a solvent, adding water, a copper (II) salt and a ligand, reacting for 4-6 h at 25-90 ℃, and separating to obtain 5-bromolevulinic acid; wherein the ligand is selected from at least one of 1, 10-phenanthroline or derivatives thereof.
The preparation method of 5-bromolevulinic acid provided by the embodiment of the invention is to dissolve 5-bromo-4-pentynoic acid serving as a raw material in a solvent, and after water is added, copper (II) salt and 1, 10-phenanthroline or a derivative thereof serving as a ligand are added for heating reaction, so as to prepare the 5-bromolevulinic acid, wherein the specific reaction equation is as follows:
the preparation method of 5-bromolevulinic acid provided by the embodiment of the invention can obtain 5-bromolevulinic acid with high selectivity and high yield, and compared with a method for preparing 5-bromolevulinic acid by using levulinic acid bromination reaction, the preparation method provided by the invention overcomes the problem that the byproduct 3-bromolevulinic acid is easily generated, so that the utilization rate of raw materials is improved, and the product is easily separated.
In a preferred embodiment of the present invention, the solvent is selected from any one of trifluoroacetic acid, acetonitrile, acetic acid, dichloroethane, and toluene, or a mixture of trifluoroacetic acid and any one of acetonitrile, acetic acid, dichloroethane, and toluene. Preferably, the solvent is a mixture of trifluoroacetic acid and dichloroethane; more preferably, when the solvent consists of two raw materials, the volume ratio of the two raw materials is 1-9: 3.
in a preferred embodiment of the present invention, the copper (II) salt is selected from at least one of copper acetate monohydrate, copper trifluoroacetate, copper sulfate, copper chloride and copper bromide; preferably, the copper (II) salt is copper acetate monohydrate. The salt of divalent copper ions is used as a catalyst, and can be matched with a ligand to perform catalytic reaction to prepare the high-yield 5-bromolevulinic acid.
In a preferred embodiment of the present invention, the ligand is selected from at least one of 1, 10-phenanthroline, 2, 9-dimethyl-1, 10-phenanthroline and 3, 4, 7, 8-tetramethyl-1, 10-phenanthroline; preferably, the ligand is 1, 10-phenanthroline. The selected specific dinitrogen ligand can be effectively matched with the divalent copper ion salt, so that the raw materials are fully reacted, and the yield of the prepared 5-bromolevulinic acid is improved.
In a preferred embodiment of the invention, the mass ratio of 5-bromo-4-pentynoic acid and copper (II) salt is 1:0.01 to 0.2; preferably, the mass ratio of 5-bromo-4-pentynoic acid to copper (II) salt is 1: 0.1; more preferably, the mass ratio of 5-bromo-4-pentynoic acid to ligand is 1:0.01 to 0.2; further preferably, the mass ratio of 5-bromo-4-pentynoic acid to ligand is 1: 0.05. by selecting a proper ratio of the raw material 5-bromo-4-pentynoic acid, the catalyst copper (II) salt and the ligand, the minimum amount of the catalyst and the ligand can be used, and the raw materials can be maximally utilized to prepare the 5-bromolevulinic acid with high yield.
In a preferred embodiment of the present invention, the reaction is carried out at 75-85 ℃ for 4-5 h. By selecting proper reaction temperature and time, the generation of impurities can be reduced, and the yield of the prepared 5-bromolevulinic acid is improved.
In a preferred embodiment of the present invention, the separation is performed by column chromatography or recrystallization. Impurities in the product obtained by the preparation can be removed by using column chromatography or recrystallization to obtain 5-bromolevulinic acid with high purity.
The copper (II) salt in the present example is a divalent copper salt, TFA is an English abbreviation for trifluoroacetic acid, DCE is an English abbreviation for dichloroethane, CH3CN is the molecular formula of acetonitrile, AcOH is the English abbreviation of acetic acid, and the used chromatographic column is a silica gel column.
The features and properties of the present invention are described in further detail below with reference to examples.
Example 1
The embodiment of the invention provides 5-bromolevulinic acid, and the specific preparation method comprises the following steps:
a 100mL flask was prepared, 0.531g of 5-bromo-4-pentynoic acid (3.0mmol) was dissolved in 36mL of TFA, and after stirring uniformly, 0.162mL of water (9.0mmol) and 0.048g of anhydrous copper sulfate (0.30mmol) were added, and after heating to 70 ℃ and reacting for 4 hours, the solvent was evaporated under reduced pressure, and separation by column chromatography (eluting the adsorption column with an eluent of ethyl acetate/petroleum ether ═ 1: 3) gave 0.374g of 5-bromolevulinic acid in 64% yield.
Example 2
Example 2 the procedure of example 1 was repeated, except that the catalyst anhydrous copper sulfate was changed to 0.040g of anhydrous copper chloride (0.30mmol), and the other procedure was identical to example 1, to give 0.404g of 5-bromolevulinic acid in 69% yield.
Example 3
Example 3 the procedure of example 1 was repeated, except that the catalyst anhydrous copper sulfate was changed to 0.067g of anhydrous copper bromide (0.30mmol), and the other procedure was identical to example 1, to give 0.421g of 5-bromolevulinic acid in a yield of 72%.
Example 4
Example 4 the procedure of example 1 was repeated, except that the catalyst anhydrous copper sulfate was changed to 0.087g anhydrous copper trifluoroacetate (0.30mmol), and the other procedure was identical to example 1, to give 0.439g of 5-bromolevulinic acid in a yield of 75%.
Example 5
Example 5 the procedure of example 1 was repeated, except that the catalyst anhydrous copper sulfate was changed to 0.060g of copper acetate monohydrate (0.30mmol), and the other procedure was identical to example 1, to give 0.521g of 5-bromolevulinic acid with a yield of 89%.
Example 6
Example 6 the procedure of example 1 was followed, except that anhydrous copper sulfate was changed to 0.030g of copper acetate monohydrate (0.15mmol), and the other procedures were repeated as in example 1 to obtain 0.363g of 5-bromolevulinic acid with a yield of 62%.
Example 7
Example 7 the procedure of example 1 was repeated, except that anhydrous copper sulfate was changed to 0.120g of copper acetate monohydrate (0.6mmol), and the other procedure was repeated as in example 1 to obtain 0.521g of 5-bromolevulinic acid with a yield of 89%.
Example 8
The embodiment of the invention provides 5-bromolevulinic acid, and the specific preparation method comprises the following steps:
preparing a 100mL flask, dissolving 0.531g of 5-bromo-4-pentynoic acid (3.0mmol) into 36mL of TFA, uniformly stirring, adding 0.162mL of water (9.0mmol), 0.060g of copper acetate monohydrate (0.30mmol) and 0.027g of 1, 10-phenanthroline (0.15mmol), heating to 70 ℃ for reaction for 4h, evaporating the solvent under reduced pressure, and separating by column chromatography (eluting an adsorption column with an eluent of ethyl acetate/petroleum ether (1: 3)) to obtain 0.544g of 5-bromolevulinic acid, wherein the yield is 93%.
Example 9
The embodiment of the invention provides 5-bromolevulinic acid, and the specific preparation method comprises the following steps:
preparing a 100mL flask, dissolving 0.531g of 5-bromo-4-pentynoic acid (3.0mmol) in 36mL of TFA, uniformly stirring, adding 0.162mL of water (9.0mmol), 0.060g of copper acetate monohydrate (0.30mmol), 0.031g of 2, 9-dimethyl-1, 10-phenanthroline (0.15mmol), and heating to 70 ℃ for reacting for 4 hours. The solvent was evaporated under reduced pressure and the residue was mixed with 25mL of diethyl ether, heated under reflux, filtered to remove insoluble material, the diethyl ether solution was cooled to precipitate a solid, which was collected and dried to give 0.509g of 5-bromolevulinic acid in 87% yield.
Example 10
Example 10 the procedure of example 8 was followed in a similar manner except that 1, 10-phenanthroline was changed to 0.035g3, 4, 7, 8-dimethyl-1, 10-phenanthroline (0.15mmol), and the other procedure was followed as in example 8 to obtain 0.527g of 5-bromolevulinic acid with a yield of 90%.
Example 11
Example 11 the procedure of example 8 was similar except that 1, 10-phenanthroline was added in an amount of 0.011g (0.06mmol), and the other procedure was the same as example 8 to obtain 0.527g of 5-bromolevulinic acid with a yield of 90%.
Example 12
Example 12 the procedure of example 8 was followed except that 1, 10-phenanthroline was added in an amount of 0.054g (0.300mmol), and the other procedure was the same as example 8 to obtain 0.415g of 5-bromolevulinic acid with a yield of 71%.
Example 13
The embodiment of the invention provides 5-bromolevulinic acid, and the specific preparation method comprises the following steps:
preparing a 100mL flask, dissolving 0.531g of 5-bromo-4-pentynoic acid (3.0mmol) into 36mL of TFA, uniformly stirring, adding 0.162mL of water (9.0mmol), 0.060g of copper acetate monohydrate (0.30mmol) and 0.027g of 1, 10-phenanthroline (0.15mmol), heating to 25 ℃ for reaction for 4h, evaporating the solvent under reduced pressure, and separating by column chromatography (eluting an adsorption column with an eluent of ethyl acetate/petroleum ether (1: 3)) to obtain 0.117g of 5-bromolevulinic acid, wherein the yield is 20%.
Example 14
Example 14 similar to example 13 implementation steps, except that the reaction mixture heated to 60 degrees C reaction for 4h, other steps and example 13, obtained 5-bromine levulinic acid 0.246g, yield 42%.
Example 15
The embodiment of the invention provides 5-bromolevulinic acid, and the specific preparation method comprises the following steps:
preparing a 100mL flask, dissolving 0.885g of 5-bromo-4-pentynoic acid (5.0mmol) into a solvent formed by mixing 30mL of TFA and 30mL of DCE, uniformly stirring, adding 0.270mL of water (15.0mmol), 0.100g of copper acetate monohydrate (0.50mmol) and 0.045g of 1, 10-phenanthroline (0.25mmol), heating to 80 ℃ for reaction for 4 hours, evaporating the solvent under reduced pressure, and separating by using column chromatography (washing an adsorption column by using an eluent of ethyl acetate/petroleum ether which is 1: 3) to obtain 0.956g of 5-bromolevulinic acid, wherein the yield is 98%.
Example 16
The embodiment of the invention provides 5-bromolevulinic acid, and the specific preparation method comprises the following steps:
preparing a 100mL flask, dissolving 0.885g of 5-bromo-4-pentynoic acid (5.0mmol) into a solvent formed by mixing 30mL of TFA and 30mL of acetonitrile, uniformly stirring, adding 0.270mL of water (15.0mmol), 0.100g of copper acetate monohydrate (0.50mmol) and 0.045g of 1, 10-phenanthroline (0.25mmol), heating to 75 ℃ for reaction for 4h, evaporating the solvent under reduced pressure, and separating by using column chromatography (washing an adsorption column by using an eluent of ethyl acetate/petroleum ether ═ 1: 3) to obtain 0.780g of 5-bromolevulinic acid, wherein the yield is 80%.
Example 17
The embodiment of the invention provides 5-bromolevulinic acid, and the specific preparation method comprises the following steps:
preparing a 100mL flask, dissolving 0.885g of 5-bromo-4-pentynoic acid (5.0mmol) into a solvent formed by mixing 30mL of TFA and 30mL of AcOH, uniformly stirring, adding 0.270mL of water (15.0mmol), 0.100g of copper acetate monohydrate (0.50mmol) and 0.045g of 1, 10-phenanthroline (0.25mmol), heating to 75 ℃ for reaction for 4h, evaporating the solvent under reduced pressure, and separating by using column chromatography (washing an adsorption column by using an eluent of ethyl acetate/petroleum ether which is 1: 3) to obtain 0.800g of 5-bromolevulinic acid, wherein the yield is 82%.
Example 18
The embodiment of the invention provides 5-bromolevulinic acid, and the specific preparation method comprises the following steps:
preparing a 100mL flask, dissolving 0.885g of 5-bromo-4-pentynoic acid (5.0mmol) in 60mL of acetic acid, uniformly stirring, adding 0.270mL of water (15.0mmol), 0.100g of copper acetate monohydrate (0.50mmol) and 0.045g of 1, 10-phenanthroline (0.25mmol), heating to 75 ℃ for reaction for 4 hours, evaporating the solvent under reduced pressure, and separating by column chromatography (washing an adsorption column by using an eluent of ethyl acetate/petroleum ether 1: 3) to obtain 0.663g of 5-bromolevulinic acid, wherein the yield is 68%.
Example 19
The embodiment of the invention provides 5-bromolevulinic acid, and the specific preparation method comprises the following steps:
preparing a 100mL flask, dissolving 0.885g of 5-bromo-4-pentynoic acid (5.0mmol) into a solvent formed by mixing 30mL of TFA and 30mL of toluene, uniformly stirring, adding 0.270mL of water (15.0mmol), 0.100g of copper acetate monohydrate (0.50mmol) and 0.045g of 1, 10-phenanthroline (0.25mmol), heating to 75 ℃ for reaction for 4h, evaporating the solvent under reduced pressure, and separating by using column chromatography (washing an adsorption column by using an eluent of ethyl acetate/petroleum ether which is 1: 3) to obtain 0.741g of 5-bromolevulinic acid, wherein the yield is 76%.
Example 20
The embodiment of the invention provides 5-bromolevulinic acid, and the specific preparation method comprises the following steps:
preparing a 100mL flask, dissolving 0.885g of 5-bromo-4-pentynoic acid (5.0mmol) into a solvent formed by mixing 30mL of TFA and 30mL of DCE, uniformly stirring, adding 0.270mL of water (15.0mmol), 0.100g of copper acetate monohydrate (0.50mmol) and 0.045g of 1, 10-phenanthroline (0.25mmol), heating to 80 ℃ for reaction for 3h, evaporating the solvent under reduced pressure, and separating by using column chromatography (washing an adsorption column by using an eluent of ethyl acetate/petroleum ether which is 1: 3) to obtain 0.809g of 5-bromolevulinic acid, wherein the yield is 83%.
The results of nuclear magnetic resonance detection of 5-bromolevulinic acid prepared in the embodiment of the invention are shown in figures 1 and 2, and the nuclear magnetic resonance hydrogen spectrum thereof1H NMR(600MHz，CDCl3)：δ3.95(s，2H，BrCH2-)，2.96(t，J＝12.6Hz，2H，-COCH2-)，2.70(t，J＝12.6Hz，2H，-CH2COO-); nuclear magnetic resonance carbon spectrum13C NMR(150MHz，CDCl3)：δ170.7，170.6，52.2，41.2，22.7。
In conclusion, the preparation method of 5-bromolevulinic acid provided by the embodiment of the invention does not generate 3-bromolevulinic acid as a byproduct, has the advantages of high utilization rate of raw materials, low cost of the catalyst, easy separation and high yield of products, and is simple, reliable and easy to operate, and suitable for large-scale preparation of 5-bromolevulinic acid.
The embodiments described above are some, but not all embodiments of the invention. The detailed description of the embodiments of the present invention is not intended to limit the scope of the invention as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Claims (7)
1. A preparation method of 5-bromolevulinic acid is characterized by comprising the following steps: dissolving 5-bromo-4-pentynoic acid in a solvent, adding water, a copper (II) salt and a ligand, reacting for 4-6 h at 70-90 ℃, and separating to obtain 5-bromolevulinic acid;
wherein the ligand is selected from at least one of 1, 10-phenanthroline or derivatives thereof;
the mass ratio of the 5-bromo-4-pentynoic acid to the copper (II) salt is 1:0.01 to 0.2, and the mass ratio of the 5-bromo-4-pentynoic acid to the ligand is 1:0.01 to 0.2.
2. The method for producing 5-bromolevulinic acid according to claim 1, wherein the solvent is selected from any one of trifluoroacetic acid, acetonitrile, acetic acid, dichloroethane, and toluene, or a mixture of trifluoroacetic acid and any one of acetonitrile, acetic acid, dichloroethane, and toluene.
3. The method according to claim 1, wherein the solvent is a mixture of trifluoroacetic acid and dichloroethane.
4. The method of claim 1, wherein the copper (II) salt is at least one selected from the group consisting of copper acetate monohydrate, copper trifluoroacetate, copper sulfate, copper chloride and copper bromide.
5. The method for preparing 5-bromolevulinic acid according to claim 1, wherein the ligand is at least one selected from the group consisting of 1, 10-phenanthroline, 2, 9-dimethyl-1, 10-phenanthroline, and 3, 4, 7, 8-tetramethyl-1, 10-phenanthroline.
6. The method for preparing 5-bromolevulinic acid according to claim 1, wherein the reaction is carried out at 75 to 85 ℃ for 4 to 5 hours.
7. The method for producing 5-bromolevulinic acid according to claim 1, wherein the separation is performed by column chromatography or recrystallization.
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| "Exploration of Novel 2-Alkylimino-1,3-thiazolines: T-Type Calcium";Minsoo Han等;《J. Comb. Chem》;20101231;第12卷;Scheme 1 * |
| "First Catalyzed Hydration of Haloalkynes by a Recyclable Catalytic System";Huaxu Zou等;《Eur. J. Org. Chem》;20161231;Scheme 2 * |
| "Gold-Catalyzed Hydration of Haloalkynes to α‑Halomethyl Ketones";Longyong Xie等;《The Journal of Organic Chemistry》;20130816;第78卷;第9191页右栏最后一段-第9192页左栏第一段 * |
| "Probing the active site of rat porphobilinogen synthase using newly developed inhibitors";Nan Li等;《Bioorganic Chemistry》;20081217;第37卷;第37页figure 5，第37页左栏最后一段-右栏第一段 * |
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