CN115073285A - Synthetic method of 3, 5-diiodo salicyloyl chloride - Google Patents
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- GPAVORZIWQTJJQ-UHFFFAOYSA-N 2-(benzylazaniumyl)-3-methylpentanoate Chemical compound CCC(C)C(C(O)=O)NCC1=CC=CC=C1 GPAVORZIWQTJJQ-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 238000010189 synthetic method Methods 0.000 title description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 47
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 32
- DHZVWQPHNWDCFS-UHFFFAOYSA-N 2-hydroxy-3,5-diiodobenzoic acid Chemical compound OC(=O)C1=CC(I)=CC(I)=C1O DHZVWQPHNWDCFS-UHFFFAOYSA-N 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 27
- 239000002904 solvent Substances 0.000 claims abstract description 23
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910021389 graphene Inorganic materials 0.000 claims abstract description 12
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 238000010992 reflux Methods 0.000 claims abstract description 11
- 238000010438 heat treatment Methods 0.000 claims abstract description 10
- 238000003756 stirring Methods 0.000 claims abstract description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 42
- ODXPJUJPWFDXOR-UHFFFAOYSA-N 2-hydroxy-3,5-diiodobenzoyl chloride Chemical compound OC1=C(I)C=C(I)C=C1C(Cl)=O ODXPJUJPWFDXOR-UHFFFAOYSA-N 0.000 claims description 20
- 230000002194 synthesizing effect Effects 0.000 claims description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- 238000002390 rotary evaporation Methods 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 7
- 239000012295 chemical reaction liquid Substances 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- 150000001263 acyl chlorides Chemical class 0.000 abstract description 7
- 239000000543 intermediate Substances 0.000 abstract description 5
- 238000001308 synthesis method Methods 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 230000035484 reaction time Effects 0.000 abstract description 4
- 239000000376 reactant Substances 0.000 abstract description 3
- 230000007797 corrosion Effects 0.000 abstract description 2
- 238000005260 corrosion Methods 0.000 abstract description 2
- 239000012467 final product Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- -1 carboxylate ions Chemical class 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DVIHKVWYFXLBEM-UHFFFAOYSA-N 2-hydroxybenzoyl chloride Chemical compound OC1=CC=CC=C1C(Cl)=O DVIHKVWYFXLBEM-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000005915 ammonolysis reaction Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a synthesis method of 3, 5-diiodo salicyloyl chloride, belonging to the technical field of synthesis of acyl chloride medical intermediates. Adding 3, 5-diiodosalicylic acid, a catalyst, an organic solvent and thionyl chloride into a reaction vessel, heating and stirring at 40-65 ℃, carrying out reflux reaction, reacting for 1-3 hours after a reaction solution becomes clear, and removing the solvent to obtain the 3, 5-diiodosalicyloyl chloride. According to the method, graphene oxide is introduced as a catalyst for the first time, reaction sites can be increased by the graphene oxide, the reaction can be rapidly initiated, the reaction is easier to carry out, and the reaction temperature, the reactant proportion and the reaction time are optimized. The method has the advantages of high atom economy of chemical reaction, high purity of the 3, 5-diiodo salicyloyl chloride up to 99.9%, high yield up to 99.6%, mild reaction conditions, obvious reduction of corrosion and loss to reaction equipment, easy operation and simple post-treatment.
Description
Technical Field
The invention relates to a synthesis method of 3, 5-diiodo salicyloyl chloride, belonging to the technical field of synthesis of acyl chloride medical intermediates.
Background
The pharmaceutical intermediates are fine chemical products with high added values, are various in types, strong in matching, high in added value, good in economic benefit and short in market, and are the main way for enterprises to seek new economic growth points. The acyl chloride compound is a compound containing a functional group-C (O) Cl, is a very important organic intermediate, has very active property, can react with water to generate carboxylic acid, reacts with ammonia or amine to generate amide (ammonolysis), reacts with alcohol to generate ester (alcoholysis), reacts with carboxylate ions to generate anhydride, reacts with Grignard reagent to generate ketone or alcohol, and can be reduced to alcohol or aldehyde by hydrogen. By utilizing the active groups and the catalytic action in the acyl chloride compound, a plurality of pharmaceutical and chemical products and intermediates thereof with novel structures and excellent performance can be synthesized, and meanwhile, preparation approaches of some pharmaceutical derivatives can be provided, and the preparation method has wide application in the aspects of medicines, pesticides, resource environments and the like.
3, 5-diiodosalicyloyl chloride is an acyl chloride compound, is used for synthesizing various raw material medicaments and biochemical reagents as a medical intermediate, and the conventional synthesis method is to react 3, 5-diiodosalicylic acid with an acyl chloride reagent, but the molecular structure of the compound contains not only carboxyl but also phenolic hydroxyl. In general, the acid chloride reagent will preferentially react with the carboxyl group to give the acid chloride. However, when the acyl chlorination reagent is in excess or the reaction conditions are severe, the phenolic hydroxyl group in the molecule also participates in the reaction and is substituted by chlorine atom. In addition, the acyl chloride compound is active in property, is easy to react with water to deteriorate, and is not suitable for being exposed in air for a long time, so that the requirements on the treatment and purification processes of the product are strict. Most of the commercially available 3, 5-diiodo salicyl chloride has a purity of only 98% at the maximum.
Wuyuelin et al reported a synthesis route of 3, 5-diiodo salicyloyl chloride (Wuyuelin et al, "research on synthesis process of 3, 5-diiodo salicyloyl chloride," national society of academic exchange of fine chemical engineering, China chemical society, 2002.), mainly comprising the reaction of 3, 5-diiodo salicylic acid with thionyl chloride, using chlorobenzene as a solvent, and having the following reaction formula:
under the process conditions, the purity of the product is 98.3%, the yield is only 69.3%, the boiling point of chlorobenzene is 132 ℃, the solvent is difficult to evaporate in the post-treatment process, the product purification difficulty is high, and the production energy consumption cost and the time cost are both obviously increased. The high-temperature reaction has higher requirements on production equipment, and the corresponding potential safety hazard is increased.
Wang et al reported that salicyloyl chloride was synthesized by refluxing at 40 ℃ using methylene chloride as a solvent and thionyl chloride as an acid chlorinating agent (Wang, S., et al, "Scaffold university by the Natural Product odor: Discovery of high elevation post and Multitargeting anti Agents," Journal of medical Chemistry (2015):6678.), the reaction formula was as follows:
however, the salicyl chloride in the literature is only an intermediate product in the whole synthesis reaction process, the obtained product is directly used for the next reaction, the reaction temperature and the reaction time are not optimized, the yield of the obtained salicyl chloride is 98%, and the purity is not explicitly reported.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention aims to provide a method for synthesizing 3, 5-diiodo salicyloyl chloride.
In order to achieve the purpose of the invention, the following technical scheme is provided.
A method for synthesizing 3, 5-diiodo salicyl chloride comprises the following steps:
adding 3, 5-diiodosalicylic acid, a catalyst, an organic solvent and thionyl chloride into a reaction vessel, heating and stirring at 40-65 ℃ for reflux reaction, reacting for 1-3 hours after reaction liquid becomes clear, and removing the solvent to obtain solid powder, namely 3, 5-diiodosalicyloyl chloride. The reaction formula is as follows:
wherein the catalyst is graphene oxide.
The organic solvent is a mixed solution of a solvent A, hexane and the solvent A or a mixed solution of dichloroethane and the solvent A, and the solvent A is at least one of pentane, dichloromethane and chloroform.
The molar ratio of the 3, 5-diiodosalicylic acid to the thionyl chloride is 1: 1.5-1: 5, preferably 1: 1.5-1: 3.
The molar ratio of the 3, 5-diiodosalicylic acid to the catalyst is 50: 1-400: 1, preferably 100: 1-200: 1.
The mass ratio of the 3, 5-diiodosalicylic acid to the organic solvent is 1: 10-1: 100, preferably 1: 15-1: 50.
Preferably, the heating temperature is 45 ℃ to 60 ℃.
Preferably, the reaction solution is clarified and then reacted for 1-2 hours.
Preferably, the solvent is removed by rotary evaporation under reduced pressure.
Advantageous effects
1. The invention provides a synthesis method of 3, 5-diiodo salicyloyl chloride, which introduces graphene oxide as a catalyst for the first time, wherein the graphene oxide can increase reaction sites and quickly initiate a reaction, so that the reaction is easier to carry out; the method has high atom economy of chemical reaction, the 3, 5-diiodosalicylic acid as the raw material is basically and completely reacted, and the yield can reach 99.6 percent to the maximum.
2. The invention provides a method for synthesizing 3, 5-diiodo salicyloyl chloride, which optimizes the reaction temperature, the reactant proportion and the reaction time, and can accelerate the reflux reaction at the reaction temperature of 40-65 ℃ and ensure that the hydroxyl on the benzene ring of the raw material 3, 5-diiodo salicyloyl chloride cannot be replaced by chlorine atoms in thionyl chloride to generate byproducts; the purity of the product is further improved by optimizing the reactant proportion and the reaction time, and the purity of the 3, 5-diiodo salicyloyl chloride prepared by the method can reach 99.9 percent to the maximum.
3. The invention provides a synthesis method of 3, 5-diiodo salicyloyl chloride, which has mild reaction conditions, obviously reduces the corrosion and loss to reaction equipment, is easy to operate and has simple post-treatment.
Drawings
FIG. 1 is an infrared spectrum of 3, 5-diiodosalicyloyl chloride prepared in example 1 and 3, 5-diiodosalicylic acid as a raw material.
FIG. 2 is a liquid chromatogram of the reaction of 3, 5-diiodosalicyl chloride obtained in example 1 with methanol to produce methyl carboxylate.
FIG. 3 shows the reaction of 3, 5-diiodosalicyl chloride prepared in example 1 in CDCl 3 In (1) 1 H-NMR spectrum.
Detailed Description
The invention is described in detail below with reference to the drawings and specific examples, but the invention is not limited thereto.
The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
Example 1
A method for synthesizing 3, 5-diiodo salicyl chloride comprises the following steps:
30mmol of 3, 5-diiodosalicylic acid, 0.3mmol of graphene oxide, dichloromethane and 45mmol of thionyl chloride are added into a 250mL three-necked flask, and the mass ratio of the 3, 5-diiodosalicylic acid to the dichloromethane is 1: 15. Heating and stirring at 55 ℃ for reflux reaction, reacting for 1.5 hours after the reaction solution becomes clear, and distilling under reduced pressure to remove the solvent to obtain a final product which is yellow solid powder with the mass of 12.18 g.
Example 2
A method for synthesizing 3, 5-diiodo salicyl chloride comprises the following steps:
adding 30mmol of 3, 5-diiodosalicylic acid, 0.3mmol of graphene oxide, dichloromethane and 90mmol of thionyl chloride into a 250mL three-necked flask, wherein the mass ratio of the 3, 5-diiodosalicylic acid to the dichloromethane is 1:15, heating, stirring and refluxing at 45 ℃, reacting for 1.5 hours after a reaction solution becomes clear, and carrying out reduced pressure rotary evaporation to remove a solvent to obtain a final product which is yellow solid powder with the mass of 12.19 g.
Example 3
A method for synthesizing 3, 5-diiodo salicyl chloride comprises the following steps:
30mmol of 3, 5-diiodosalicylic acid, 0.15mmol of graphene oxide, dichloromethane and 45mmol of thionyl chloride are added into a 250mL three-necked flask, the mass ratio of 3, 5-diiodosalicyloyl chloride to dichloromethane is 1:15, the mixture is heated and stirred at 55 ℃ for reflux reaction, the reaction solution is clarified and then reacts for 1.5 hours, the solvent is removed by reduced pressure rotary evaporation, and the final product is yellow solid powder with the mass of 12.19 g.
Example 4
A method for synthesizing 3, 5-diiodo salicyl chloride comprises the following steps:
adding 30mmol of 3, 5-diiodosalicylic acid, 0.3mmol of graphene oxide, dichloromethane and 45mmol of thionyl chloride into a 250mL three-necked flask, heating and stirring at 55 ℃ for reflux reaction, reacting for 1 hour after the reaction liquid becomes clear, and carrying out reduced pressure rotary evaporation to remove the solvent to obtain a final product which is yellow solid powder with the mass of 12.18g, wherein the mass ratio of the 3, 5-diiodosalicylic acid to the dichloromethane is 1: 50.
Example 5
A method for synthesizing 3, 5-diiodo salicyl chloride comprises the following steps:
adding 30mmol of 3, 5-diiodosalicylic acid, 0.3mmol of graphene oxide, an organic solvent and 45mmol of thionyl chloride into a 250mL three-necked flask, wherein the organic solvent is a mixed solvent of dichloromethane and n-hexane, the mass ratio of 3, 5-diiodosalicyloyl chloride to the organic solvent is 1:50, heating and stirring at 60 ℃, carrying out reflux reaction, reacting for 3 hours after the reaction liquid becomes clear, and carrying out reduced pressure rotary evaporation to remove the solvent, so as to obtain a final product which is yellow solid powder with the mass of 12.19 g.
Example 6
A method for synthesizing 3, 5-diiodo salicyl chloride comprises the following steps:
30mmol of 3, 5-diiodosalicylic acid, 0.3mmol of graphene oxide, dichloromethane and 90mmol of thionyl chloride are added into a 250mL three-necked flask, the mass ratio of the 3, 5-diiodosalicylic acid to the dichloromethane is 1:30, the mixture is heated and stirred at 55 ℃ for reflux reaction, the reaction liquid is reacted for 2.5 hours after becoming clear, and the solvent is removed by reduced pressure rotary evaporation, so that the final product is yellow solid powder with the mass of 12.20 g.
Infrared spectroscopy was performed on the final product prepared in example 1 and the starting material, 3, 5-diiodosalicylic acid, and the results are shown in FIG. 1. As can be seen from FIG. 1, 3, 5-diiodosalicyloyl chloride is 3200cm in length compared with 3, 5-diiodosalicylic acid as a raw material -1 ～2500cm -1 Disappearance of broad peak of (1788 cm) -1 And 1752cm -1 Two peaks appear indicating that the hydroxyl group on the carboxyl group was replaced with chlorine and changed to an acid chloride. The end product of example 1 was demonstrated to be 3, 5-diiodosalicyl chloride.
The infrared spectra of examples 2-6 are similar to example 1.
The final product prepared in example 1 was subjected to nmr hydrogen spectroscopy, and the results are shown in fig. 3. As can be seen from FIG. 3, the peaks are 10.45ppm(s), 8.34ppm(s) and 8.32ppm(s), respectively, which correspond to the hydroxyl hydrogen on carbon No. 6, the hydrogen on carbon No. 2 and the hydrogen on carbon No. 4 of the benzene ring, respectively. Because the chemical shifts of the hydrogens corresponding to carbons No. 2 and No. 4 are relatively close, there is some degree of overlap in the appearance of the peaks. The end product of example 1 was demonstrated to be 3, 5-diiodosalicyl chloride.
The nuclear magnetic spectra of examples 2-6 were similar to example 1.
Since 3, 5-diiodosalicyloyl chloride is active in chemical properties and cannot be directly subjected to liquid chromatography, the final product prepared in example 1 is dissolved in methanol to prepare the corresponding methyl carboxylate, and the obtained methyl carboxylate is subjected to liquid chromatography, and the result is shown in fig. 2, and the purity of the 3, 5-diiodosalicyloyl chloride prepared in example 1 is 99.3% according to the ratio of peak areas.
The liquid chromatogram of examples 2-6 was similar to that of example 1.
The purity of 3, 5-diiodosalicyloyl chloride prepared in examples 1-6 is shown in table 1:
TABLE 1 purity of 3, 5-diiodosalicyloyl chloride prepared in examples 1-6
The calculated yield of 3, 5-diiodosalicyloyl chloride prepared in examples 1-6 is shown in table 2:
TABLE 2 yield of 3, 5-diiodosalicyloyl chloride prepared in examples 1-6
The test results show that the synthetic method of the 3, 5-diiodo salicyloyl chloride has high economy of chemical reaction atoms, the yield can reach 99.6 percent at most, and the purity can reach 99.9 percent at most.
Claims (9)
1. A method for synthesizing 3, 5-diiodo salicyloyl chloride is characterized in that: the method comprises the following steps:
adding 3, 5-diiodosalicylic acid, a catalyst, an organic solvent and thionyl chloride into a reaction vessel, heating and stirring at 40-65 ℃, carrying out reflux reaction, reacting for 1-3 hours after reaction liquid becomes clear, and removing the solvent to obtain solid powder, namely 3, 5-diiodosalicyloyl chloride;
wherein the catalyst is graphene oxide;
the organic solvent is a mixed solution of a solvent A, hexane and the solvent A or a mixed solution of dichloroethane and the solvent A, and the solvent A is at least one of pentane, dichloromethane and chloroform;
the molar ratio of the 3, 5-diiodosalicylic acid to the thionyl chloride is 1: 1.5-1: 5;
the molar ratio of the 3, 5-diiodosalicylic acid to the catalyst is 50: 1-400: 1;
the mass ratio of the 3, 5-diiodosalicylic acid to the organic solvent is 1: 10-1: 100.
2. The method for synthesizing 3, 5-diiodosalicyl chloride according to claim 1, wherein: the molar ratio of the 3, 5-diiodosalicylic acid to the thionyl chloride is 1: 1.5-1: 3.
3. The method for synthesizing 3, 5-diiodosalicyl chloride according to claim 1, wherein: the molar ratio of the 3, 5-diiodosalicylic acid to the catalyst is 100: 1-200: 1.
4. The method for synthesizing 3, 5-diiodosalicyl chloride according to claim 1, wherein: the mass ratio of the 3, 5-diiodosalicylic acid to the organic solvent is 1: 15-1: 50.
5. The method for synthesizing 3, 5-diiodosalicyl chloride according to claim 1, wherein: the molar ratio of the 3, 5-diiodosalicylic acid to the thionyl chloride is 1: 1.5-1: 3; the molar ratio of the 3, 5-diiodosalicylic acid to the catalyst is 100: 1-200: 1; the mass ratio of the 3, 5-diiodosalicylic acid to the organic solvent is 1: 15-1: 50.
6. The method for synthesizing 3, 5-diiodosalicyl chloride according to any one of claims 1 to 5, wherein: the heating temperature is 45-60 ℃.
7. The method for synthesizing 3, 5-diiodosalicyl chloride according to any one of claims 1 to 5, wherein: and reacting the reaction solution for 1-2 hours after the reaction solution becomes clear.
8. The method for synthesizing 3, 5-diiodosalicyl chloride according to any one of claims 1 to 5, wherein: the solvent was removed by rotary evaporation under reduced pressure.
9. The method for synthesizing 3, 5-diiodosalicyl chloride according to any one of claims 1 to 5, wherein: the heating temperature is 45-60 ℃; reacting for 1-2 hours after the reaction solution becomes clear; the solvent was removed by rotary evaporation under reduced pressure.
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