CN108047018B - Synthetic method of ninhydrin - Google Patents
Synthetic method of ninhydrin Download PDFInfo
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- CN108047018B CN108047018B CN201711313650.1A CN201711313650A CN108047018B CN 108047018 B CN108047018 B CN 108047018B CN 201711313650 A CN201711313650 A CN 201711313650A CN 108047018 B CN108047018 B CN 108047018B
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- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000010189 synthetic method Methods 0.000 title claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 6
- 238000006467 substitution reaction Methods 0.000 claims abstract description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 33
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
- UHKAJLSKXBADFT-UHFFFAOYSA-N 1,3-indandione Chemical compound C1=CC=C2C(=O)CC(=O)C2=C1 UHKAJLSKXBADFT-UHFFFAOYSA-N 0.000 claims description 13
- 239000007788 liquid Substances 0.000 claims description 9
- 235000010288 sodium nitrite Nutrition 0.000 claims description 8
- 229920002472 Starch Polymers 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 235000019698 starch Nutrition 0.000 claims description 7
- 239000008107 starch Substances 0.000 claims description 7
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 6
- 239000012043 crude product Substances 0.000 claims description 6
- 229910017604 nitric acid Inorganic materials 0.000 claims description 6
- 239000002244 precipitate Substances 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- 238000000605 extraction Methods 0.000 claims description 5
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 4
- 239000001110 calcium chloride Substances 0.000 claims description 4
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 3
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 claims description 3
- ZQQVLLUALVAKKD-UHFFFAOYSA-N 2-nitrosoindene-1,3-dione Chemical compound C1=CC=C2C(=O)C(N=O)C(=O)C2=C1 ZQQVLLUALVAKKD-UHFFFAOYSA-N 0.000 claims description 2
- NNEAKBWZBQOQDH-UHFFFAOYSA-N 3-(1h-inden-2-yl)pyridine Chemical compound C=1C2=CC=CC=C2CC=1C1=CC=CN=C1 NNEAKBWZBQOQDH-UHFFFAOYSA-N 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 3
- WVZWEMOFSIEEMU-UHFFFAOYSA-N indene-1,2,3-trione Chemical compound C1=CC=C2C(=O)C(=O)C(=O)C2=C1 WVZWEMOFSIEEMU-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 6
- 238000006396 nitration reaction Methods 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000010923 batch production Methods 0.000 abstract description 2
- 125000005594 diketone group Chemical group 0.000 abstract description 2
- 230000003647 oxidation Effects 0.000 abstract description 2
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- LWFPYLZOVOCBPZ-UHFFFAOYSA-N hydrindantin Chemical compound O=C1C2=CC=CC=C2C(=O)C1(O)C1(O)C(=O)C2=CC=CC=C2C1=O LWFPYLZOVOCBPZ-UHFFFAOYSA-N 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002274 desiccant Substances 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LWWPFGMJMOLTIM-UHFFFAOYSA-N 3-nitroso-3H-indene-1,2-dione Chemical compound O=NC1C(=O)C(=O)c2ccccc12 LWWPFGMJMOLTIM-UHFFFAOYSA-N 0.000 description 1
- ATEFPOUAMCWAQS-UHFFFAOYSA-N 7,8-dihydroxycoumarin Chemical compound C1=CC(=O)OC2=C(O)C(O)=CC=C21 ATEFPOUAMCWAQS-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulphite Substances [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/75—Reactions with formaldehyde
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
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- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthetic method of ninhydrin, which comprises the following reaction route:
. The invention provides a new preparation method of ninhydrin, namely, a product with better quality is prepared by selecting appropriate diketone compounds through nitration reaction and substitution (oxidation) reaction, the yield is improved to more than 60 percent, the toxicity of the used raw materials is greatly reduced, the cost is reduced, and the preparation method is suitable for batch production.
Description
Technical Field
The invention relates to a synthesis method of ninhydrin, in particular to synthesis of 2, 2-dihydroxy-1H-indeno-1, 3(2H) -diketone.
Background
Ninhydrin has the formula 2, 2-dihydroxy-1H-indeno-1, 3(2H) -dione, english name: ninhydrin hydrate, formula C9H6O4. The product is white or yellowish crystal, and is heated to above 100 deg.C or kept for a long time to turn red. The product can form dark blue or red substance when meeting alpha-amino acid or any alpha-amino-containing substance in solution, so the product is commonly used as a reagent for prion degradation and alpha-amino compounds and is used for identifying amino acid, protein, polypeptide, vitamin C and the like.
According to the past foreign literature, Journal of the American Chemical Society (1933) reports that the product can be cyclized, hydrolyzed and decarboxylated by diethyl phthalate and ethyl acetate to obtain indan-1, 3-dione, and then selenium dioxide is added in the presence of dioxane to oxidize to obtain ninhydrin, the yield is usually below 40%, and the selenium dioxide required by the process is easy to deliquesce in air and toxic and harmful to human body.
Disclosure of Invention
In order to solve the problems, the invention provides a synthetic method of ninhydrin.
In order to achieve the purpose, the technical scheme of the invention is as follows:
the synthetic method of ninhydrin comprises the following reaction route:
preferably, step S1 specifically includes the following operations:
dissolving indane-1, 3-dione in ethanol, adding a sulfuric acid solution, dropwise adding a sodium nitrite solution, controlling the reaction temperature to be 15-20 ℃, and testing the reaction end point by using potassium iodide starch test paper to obtain the fine powder 2-nitroso-1H-indene-1, 3(2H) -dione.
Preferably, the mass fraction of the sulfuric acid solution is 50-60%, and the mass fraction of the sodium nitrite solution is 25-30%.
Preferably, in step S1, the reaction is terminated by using a potassium iodide starch strip until no color is developed.
Preferably, step S2 specifically includes the following operations:
carrying out substitution reaction on 2-nitroso-1H-indene-1, 3(2H) -diketone and formaldehyde at 15-20 ℃ in the presence of hydrochloric acid to obtain indene-1, 2, 3-triketone.
Preferably, the mass fraction of the hydrochloric acid is 25-30%, and the mass fraction of the formaldehyde is 35-37%.
Preferably, step S3 specifically includes the following operations:
adding ninhydrin-1, 2,3 into the extraction liquid, separating out a precipitate, and drying the precipitate at 50-60 ℃ under reduced pressure to obtain hydrindantin; the extraction liquid is a solution composed of sodium hydrosulfite and 35-37 wt% of industrial formaldehyde in a mass ratio of 1: 1.
Preferably, step S4 specifically includes the following operations:
carrying out oxidation reaction on the ninhydrin in a nitric acid solution at 60-80 ℃ to obtain a ninhydrin crude product, recrystallizing the ninhydrin crude product and water in a mass ratio of 1:5, drying the obtained solid with calcium chloride, and carrying out vacuum drying at 45-50 ℃ to obtain ninhydrin.
The invention provides another preparation method of ninhydrin, namely, a product with better quality is prepared by selecting appropriate diketone compounds through nitration reaction and substitution (oxidation) reaction, the yield is improved to more than 60 percent, the toxicity of the used raw materials is greatly reduced, the cost is reduced, and the preparation method is suitable for batch production.
Therefore, the invention has the advantages that:
1. according to the invention, the appropriate raw material indane-1, 3-dione is selected and prepared into ninhydrin through three steps of reactions, so that the reaction process is optimized, the quality is high, and the reaction yield is high;
2. in the nitration reaction, the indane-1, 3-dione is dissolved in the ethanol, the substances are more uniform, the concentration of the acidic liquid is 50-60% of sulfuric acid solution, and the concentration of the sodium nitrite solution adopted in the nitration reaction is 25-30%.
3. In the substitution reaction, 25-30% of hydrochloric acid and 35-37% of formaldehyde are prepared, nitroso-indene dione is added, the mixture is uniformly stirred and cooled to 15-20 ℃, an extraction liquid which is composed of sodium hydrosulfite and 35-37% of industrial formaldehyde in a ratio of 1:1 is added into the diluted solution, and the separated precipitate is treated to obtain the reductionne.
4. In the oxidation reaction, the ninhydrin is mixed in a nitric acid solution with the concentration of 10-15%, and the mixture is heated in a water bath to complete the reaction at a certain temperature.
5. The crude product obtained by the oxidation reaction is recrystallized in water at a certain temperature, the prepared product is put into a stainless steel disc, calcium chloride is used as a drying agent, and the product is dried in a vacuum oven under reduced pressure to obtain ninhydrin with better quality, the melting point range is 240-245 ℃, the content is more than 96 percent, and the ninhydrin yield is 65.2 percent based on raw material indane-1, 3-dione.
Drawings
Other features, objects and advantages of the invention will become more apparent upon reading of the detailed description of non-limiting embodiments with reference to the following drawings:
FIG. 1 shows preparation of ninhydrin according to the invention13CNMR (nuclear magnetic resonance spectroscopy);
FIG. 2 shows preparation of ninhydrin according to the invention1HNMR (nuclear magnetic spectrum);
FIG. 3 is a mass spectrum of ninhydrin prepared by the invention.
Detailed Description
The present invention will be described in detail with reference to specific examples. The following examples will aid those skilled in the art in further understanding the present invention, but are not intended to limit the invention in any manner. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention.
Example 1
(1) Adding 1000 ml of ethanol into a 3000 ml three-neck glass flask, respectively adding 146 g (1mol) of indan-1, 3-dione into the flask under stirring to dissolve the indan-1, 3-dione, adding 600 g of 50-60% sulfuric acid solution, slowly adding 700 g of 30% sodium nitrite solution dropwise under vigorous stirring (the sodium nitrite solution is not too much), controlling the reaction temperature to be between 15 and 20 ℃ until potassium iodide starch test paper does not develop color, using the reaction temperature for 1 to 2 hours, completely converting the indan-1, 3-dione into fine powder 2-nitroso-1H-indenedione, performing suction filtration on crystals (50% of excessive ethanol can be recovered in the reaction), fully washing the crystals with pure water, and drying the crystals to obtain 162 g, and measuring the boiling point range of the crystals to be 355.5-357.0C (at760 mmHg).
(2) Putting 850 g of 25-30% hydrochloric acid and 460 g of 35-37% industrial formaldehyde into a 3000 ml three-neck glass flask, intensively stirring to uniformly cool the mixture to 15-20 ℃, adding 162 g of the 2-nitroso-1H-indandione, stirring for 2-3 hours, diluting with 1200 ml of water, adding into a 5000 ml beaker, quickly adding a self-made extract (a solution consisting of 90 g of low-sodium sulfite and 90 g of 35-37% industrial formaldehyde), immediately precipitating and precipitating, filtering, sufficiently washing with pure water to pH 5-7, washing with a small amount of ethanol until the washing liquid is colorless, drying in a glass rotary evaporator under reduced pressure, keeping the temperature at 50-60 ℃ for 1.5-2.0 hours to obtain 132 g of reduced ninhydrin, wherein the melting point ranges from 248-252 ℃.
(3) Mixing 132 g of the ninhydrin with the following solution (500 ml of water and 85 g of 70% nitric acid), heating in a water bath, rapidly stirring, keeping the temperature at 60-80 ℃ for 40-50 minutes, releasing nitric oxide gas in the reaction, expanding the solution until the solution becomes thin, filtering out a small amount of insoluble substances, and cooling the filtrate to 0-5 ℃.
(4) Recrystallizing the filtered crude product in water according to the ratio of 1:5, adding 7-10 g of activated carbon, controlling the temperature to be 50-60 ℃, cooling the filtrate to be 0-5 ℃, placing the filtered solid into a stainless steel disc, drying the solid in a vacuum oven under reduced pressure for 5-6 hours (a small amount of calcium chloride is placed in the oven as a drying agent), keeping the temperature at 45-50 ℃ to obtain 116 g of white crystalline solid, wherein the melting point is 240-245 ℃, the yield of ninhydrin is 65.2 percent and the content is 96.7 percent based on indan-1, 3-dione.
The ninhydrin prepared in this example was subjected to mass spectrometry and nuclear magnetic detection, and the spectrograms are shown in fig. 1, fig. 2 and fig. 3, respectively, wherein in the nuclear magnetic spectrum,13CNMR (DMSO) has characteristic peaks at 196.93ppm, 138.40ppm, 137.13ppm, 123.78ppm, 87.51ppm respectively; 1HNMR (DMSO) produced chemical shifts of hydrogen at 8.082ppm, 8.052ppm, 8.040ppm, 8.034ppm, 7.530ppm, respectively.
Example 2
In example 1(1), the other conditions were not changed, that is, 1000 ml of ethanol was added to a 3000 ml three-necked glass flask, 146 g of indane-1, 3-dione and 600 g of 50% sulfuric acid solution were added thereto, 900 g of 25% sodium nitrite solution was slowly dropped while vigorously stirring, the reaction temperature was controlled at 15 ℃ to 20 ℃ until no color development was detected by potassium iodide starch paper, and the reaction time was 1 to 2 hours, 160 g of 2-nitroso-1H-indandione was obtained.
Example 3:
in example 1(1), under the same conditions, 850 g (25-30%) of hydrochloric acid and 460 g of 35-37% of industrial formaldehyde are placed into a 3000 ml three-neck glass flask, the mixture is uniformly cooled to 15-20 ℃ by stirring, 162 g of 2-nitroso-1H-indandione is added, the mixture is stirred for 2-3 hours, the diluted mixture is diluted with 1200 ml of water, a little of activated carbon is added, the mixture is filtered into a 5000 ml beaker, a self-made extract (a solution consisting of 80 g of sodium formaldehyde sulfoxylate and 200 g of water) is added, precipitates are immediately separated out, the filtrate is fully washed with pure water until the pH value is 5-7, a small amount of ethanol is used for washing until the washing liquid is colorless, the washing liquid is dried in a glass rotary evaporator under reduced pressure, the temperature is kept between 50-60 ℃, 1.5-2.0 hours are needed, 129 g of reduced ninhydrin is obtained, and the melting point range is 245-250 ℃.
Example 4:
in example 1(3), 132 g of ninhydrin was mixed with the following solution (500 ml of water and 120 g of 70% nitric acid), heated in a water bath, rapidly stirred, kept at 60 to 80 ℃ for 40 to 50 minutes, and the other steps and conditions were not changed, and the obtained solid was recrystallized and dried to obtain 115 g of ninhydrin, the melting point range was 240 to 245 ℃, and the yield of ninhydrin was 64.6% based on indane-1, 3-dione.
Example 5:
in example 1 and 2, 140 g of the ninhydrin B substance was mixed with the following solution (500 ml of water and 45 g of 70% nitric acid), heated in a water bath and rapidly stirred, the temperature was maintained at 60 to 80 ℃ for 70 to 80 minutes, the other steps and conditions were not changed, and the obtained solid was recrystallized and dried to obtain 109.5 g of ninhydrin, the melting point range was 240 to 245 ℃, and the ninhydrin yield was 61.52% based on indane-1, 3-dione.
Therefore, the invention is not limited to the specific embodiments, but rather, all changes and modifications that can be made without departing from the spirit and scope of the invention are intended to be embraced by the appended claims.
Claims (4)
1. The synthetic method of ninhydrin is characterized by comprising the following reaction route:
wherein: step S1 specifically includes the following operations:
dissolving indane-1, 3-dione in ethanol, adding sulfuric acid solution, dropwise adding sodium nitrite solution, controlling the reaction temperature to be 15-20 ℃, testing the reaction end point by using potassium iodide starch test paper to obtain fine powder 2-nitroso-1H-indene-1, 3(2H) -dione,
step S2 specifically includes the following operations:
carrying out substitution reaction on 2-nitroso-1H-indene-1, 3(2H) -diketone and formaldehyde at 15-20 ℃ in the presence of hydrochloric acid to obtain indene-1, 2, 3-triketone,
step S3 specifically includes the following operations:
adding indene-1, 2,3 trione into the extraction liquid, separating out a precipitate, and drying the precipitate under reduced pressure at 50-60 ℃ to obtain the ninhydrin; the extraction liquid is a solution composed of sodium hydrosulfite and 35-37 wt% of industrial formaldehyde in a mass ratio of 1:1,
step S4 specifically includes the following operations:
carrying out oxidation reaction on the ninhydrin in a nitric acid solution at 60-80 ℃ to obtain a ninhydrin crude product, recrystallizing the ninhydrin crude product and water in a mass ratio of 1:5, drying the obtained solid with calcium chloride, carrying out vacuum drying at 45-50 ℃ to obtain ninhydrin,
the yield of the ninhydrin is improved to more than 60%.
2. The method for synthesizing ninhydrin according to claim 1, wherein the mass fraction of the sulfuric acid solution is 50 to 60% and the mass fraction of the sodium nitrite solution is 25 to 30%.
3. The method for synthesizing ninhydrin according to claim 1, wherein in step S1, the reaction is terminated by a test using potassium iodide starch paper until no color is developed as measured by the potassium iodide starch paper.
4. The method for synthesizing ninhydrin according to claim 1, wherein the mass fraction of hydrochloric acid is 25 to 30% and the mass fraction of formaldehyde is 35 to 37%.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB993299A (en) * | 1962-11-29 | 1965-05-26 | Rhone Poulenc Sa | Process for the preparation of ninhydrin |
| GB1035180A (en) * | 1964-06-12 | 1966-07-06 | Riedel De Haen Ag | Process for the preparation of ninhydrin |
| US3366690A (en) * | 1966-06-07 | 1968-01-30 | Grace W R & Co | Production of ninhydrin |
| US3419616A (en) * | 1966-08-22 | 1968-12-31 | Grace W R & Co | Preparation of ninhydrin |
| JPS5791947A (en) * | 1980-11-28 | 1982-06-08 | Kawasaki Kasei Chem Ltd | Preparation of ninhydrin |
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2017
- 2017-12-12 CN CN201711313650.1A patent/CN108047018B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB993299A (en) * | 1962-11-29 | 1965-05-26 | Rhone Poulenc Sa | Process for the preparation of ninhydrin |
| GB1035180A (en) * | 1964-06-12 | 1966-07-06 | Riedel De Haen Ag | Process for the preparation of ninhydrin |
| US3366690A (en) * | 1966-06-07 | 1968-01-30 | Grace W R & Co | Production of ninhydrin |
| US3419616A (en) * | 1966-08-22 | 1968-12-31 | Grace W R & Co | Preparation of ninhydrin |
| JPS5791947A (en) * | 1980-11-28 | 1982-06-08 | Kawasaki Kasei Chem Ltd | Preparation of ninhydrin |
Non-Patent Citations (2)
| Title |
|---|
| "A New preparation of ninhydrin";Teeters, W. O.等;《Journal of the American Chemical Society》;19331231;第3026-3028页 * |
| "Transient Spectroscopy of Ninhydrin";Mark H. Kleinman等;《Photochemistry and Photobiology》;20031231;第10-17页 * |
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