CN1254468C - Preparation method of carboxyalkyl lotanning - Google Patents
Preparation method of carboxyalkyl lotanning Download PDFInfo
- Publication number
- CN1254468C CN1254468C CN 03114078 CN03114078A CN1254468C CN 1254468 C CN1254468 C CN 1254468C CN 03114078 CN03114078 CN 03114078 CN 03114078 A CN03114078 A CN 03114078A CN 1254468 C CN1254468 C CN 1254468C
- Authority
- CN
- China
- Prior art keywords
- mentioned
- preparation
- temperature
- carboxylic acid
- hours
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a preparation method of carboxyalkyl lotanning. The preparation method comprises preparation of a cyclized compound crude product and post treatment. The preparation of the cyclized compound crude product comprises the following steps: amino carboxylic acid and chlorocarboxylic acid are respectively formed into salt; after the amino carboxylic acid is formed into the salt, the amino carboxylic acid is resulfurized; an acidifying step and a cyclization step are orderly carried out, and the cyclized compound crude product is obtained. The post treatment of the crude product orderly comprises the following steps: a filtering step, a cooling step, a standing step, a crystallizing step, a separating step, a dissolving step, a refining step, a drying step, a pulverizing step, a sieving step and a detecting step, and finally, a finished product is prepared. Compared with the prior art, the present invention has the advantages of simple synthetic route, low requirement of purity of raw material, low environmental pollution degree and easy industrial application. Especially, the present invention has the characteristics of high purity, high yield and low cost. Before the acidifying step, a proper adjustment process ph value mode is adopted, the partial raw material is cooled in advance, and the synthesis period is shortened. The present invention can also use purified water as solvent to refine products. Various performance data of the finished product is stable. The requirements of preparing sensitive film sensitizing dye and medicine for treating diabetes can be better satisfied.
Description
Technical field the present invention relates to the preparation of heterogeneous ring compound, relates in particular to the preparation method of a kind of carboxyalkyl Lip river tannin.
Background technology 3～carboxyalkyl Lip river tannin (3～Carboxyalkyl rhodanine), the light yellow crystal powder, 145～148 ℃ of fusing points, water-soluble, be a kind of organic synthesis intermediate, as the acidic heterocyclic compound intermediate of sensitive film sensitizing dye and the raw material of treatment diabetes medicament.So far do not see the domestic report that its synthesis technique is arranged, the synthetic route and the process for refining of foreign literature report are loaded down with trivial details, ingredient requirement purity height, and reaction time is long, and environmental pollution is serious.
Summary of the invention is the defective that remedies prior art, and the present invention proposes the preparation method of a kind of carboxyalkyl Lip river tannin, and the technical scheme of employing is as follows respectively:
The preparation method of this carboxyalkyl Lip river tannin comprises preparation cyclisation thing crude product and aftertreatment thereof, it is characterized in that:
Preparation cyclisation thing crude product is first with aminocarboxylic acid, chlorinated carboxylic acid difference salify, revulcanization behind the aminocarboxylic acid salify, and acidified successively then, cyclization operation obtains cyclisation thing crude product.
The crude product aftertreatment has filtration successively, cools off, leaves standstill, crystallization, separation, dissolving, refining, dry, pulverize, screening and detect operation, make finished product at last.
In the above-mentioned aminocarboxylic acid salify operation, with dissolving in 9.5～11 kilograms of sodium hydroxide input 64～66 premium on currency, under 15～20 ℃ of temperature, again 15～18 kilograms of aminocarboxylic acids are dropped into aqueous sodium hydroxide solution earlier, make the aminocarboxylic acid salts solution of pH value=6.8～7.2, standby.
In the above-mentioned chlorinated carboxylic acid salify operation, will dissolve in 20～23 kilograms of chlorinated carboxylic acid input 58～62 premium on currency earlier, drop into 10～14 kilograms of yellow soda ash dissolvings again, make the chlorinated carboxylic acid salts solution of pH value=6.8～7.2, standby.
Revulcanization operation behind the above-mentioned aminocarboxylic acid salify under 7～12 ℃ of temperature, drops into standby aminocarboxylic acid salts solution with 12～16 liters of dithiocarbonic anhydride.
Before entering acidizing process, adopt the mode of proprietary regulate process potential of hydrogen, promptly after dropping into the chlorinated carboxylic acid salts solution, with above-mentioned two kinds of solution under 15～20 ℃ of temperature, carry out reaction in 5～6 hours, reacting liquid pH value=6.8～7.0, the temperature that input is prepared in advance by 455～465 gram sodium hydroxide and 455～465 ml waters in reaction solution is 10～15 ℃ a aqueous sodium hydroxide solution, stir after 15～25 minutes, left standstill 5～10 minutes, left standstill 10～14 hours conditioned reaction liquid pH value=8.5～8.9 again, behind conditioned reaction liquid pH value=6.8～7.2, enter acidizing process.
In the above-mentioned acidizing process, under 15～20 ℃ of temperature, in 37～41 liters of inputs of the sulfuric acid reaction solution with concentration 27～30%, regulate pH value=2～3, left standstill 3.5～4.5 hours.
In above-mentioned cyclization, the filtration operation, make reacting liquid temperature rise to 85～95 ℃, 1.8～2.2 hours ring-closure reaction time, filtered while hot thereafter by 15～20 ℃ of heating.
In the above-mentioned refrigerating work procedure, make reacting liquid temperature be reduced to 15～20 ℃ naturally by 85～95 ℃.
Above-mentionedly leave standstill, in the Crystallization Procedure, under 15～20 ℃ of temperature, leave standstill 24～28 hours after, at the uniform velocity reducing in the temperature course, stirred once in 0.5 hour at every interval, carries out crystallization.
In the above-mentioned separation circuit, till centrifuge dripping to dripless flows out in whizzer with material, make the wet type coarse crystal.
In above-mentioned dissolving, the refining step, with weight is that its pure water of 4～5 times injects the wet type coarse crystal, stirring and dissolving, feed liquid after will dissolving again is heated to 50～70 ℃, stirs after 40～60 minutes, and filtered while hot also is cooled to room temperature with filtrate, left standstill 10～14 hours, separate out pure crystal, crystal is collected in vacuum filtration again.
In above-mentioned drying, the pulverizing process, under 60～80 ℃ of temperature, crystal is dried in drying plant, be 2～2.5 hours time of drying, and material was stirred at every interval in 10～15 minutes, and with its grinding.
In the above-mentioned screening operation, the crystal sieve size is 40～60 orders.
The preparation method's of this carboxyalkyl Lip river tannin further feature is:
Abovementioned alkyl can be a methyl, also can be ethyl, can also be propyl group.
Above-mentioned aminocarboxylic acid can be a Padil, also can be alanine.
Above-mentioned chlorinated carboxylic acid can be a Monochloro Acetic Acid.
Above-mentioned Padil can substitute with alanine.
The acid that above-mentioned acidizing process adopts can be sulfuric acid, also can be hydrochloric acid.
The solvent that above-mentioned dissolving, refining step adopt can be a pure water, also can be ethanol.
The present invention's beneficial effect against existing technologies is, the synthetic route of the inventive method is simple, and material purity requires low, and the environmental pollution degree is light, is easy to industrial applications, especially has high purity, high yield, characteristics cheaply.Before acidizing process, adopted proprietary regulate process potential of hydrogen mode, part material is carried out pre-cooled, can shorten synthesis cycle, can also make the solvent treatment product with pure water.Every performance index of finished product are stable, can satisfy the requirement of producing sensitive film sensitizing dye and treatment diabetes medicament preferably.
The preparation method of a kind of carboxyalkyl of embodiment Lip river tannin
The preparation method of this carboxyalkyl Lip river tannin comprises preparation cyclisation thing crude product and aftertreatment thereof.
When alkyl is substituent methyl, the component that this preparation method adopted is as follows: 16.5 kilograms of major ingredient Padils, 21.8 kilograms of Monochloro Acetic Acids, dithiocarbonic anhydride: 14.7 liters, and 39.2 liters in the sulfuric acid of 10.5 kilograms in auxiliary material sodium hydroxide, 12 kilograms in yellow soda ash, 29% concentration.
Preparation cyclisation thing crude product is first with Padil, Monochloro Acetic Acid difference salify, revulcanization behind the Padil salify, and acidified successively then, cyclization operation obtains cyclisation thing crude product.
The crude product aftertreatment has filtration successively, cools off, leaves standstill, crystallization, separation, dissolving, refining, dry, pulverize, screening and detect operation, make finished product at last.
Earlier 10.5 kilograms of sodium hydroxide are dropped in 65.2 premium on currency and dissolve, under 16～18 ℃ of temperature, again 16.5 kilograms of Padils are dropped into aqueous sodium hydroxide solution, make the Glycinates solution for standby of pH value=6.8～7.2, under 7～12 ℃ of temperature, 14.7 liters of dithiocarbonic anhydride are dropped into standby Padil salts solution again.Again 21.8 kilograms of Monochloro Acetic Acids are dropped in 59 premium on currency and dissolve, drop into 12 kilograms of yellow soda ash dissolvings again, make the chloracetic acid salts solution of pH value=6.8～7.2, standby.
With above-mentioned two kinds of solution under 16～18 ℃ of temperature, carry out reaction in 5 hours, reacting liquid pH value=6.8～7.0, the temperature that input is prepared in advance by 458 gram sodium hydroxide and 458 ml waters in reaction solution is 12～14 ℃ a aqueous sodium hydroxide solution, stirs after 20 minutes, leaves standstill 8 minutes, conditioned reaction liquid pH value=8.7, left standstill again 12 hours, and behind conditioned reaction liquid pH value=6.9, entered acidizing process.
After from reaction solution, reclaiming dithiocarbonic anhydride, under 16～18 ℃ of temperature, in 39 liters of inputs of the sulfuric acid reaction solution with concentration 29%, regulate pH value=2.8, left standstill 4 hours.Then, make reacting liquid temperature rise to 90 ℃, 2 hours ring-closure reaction time, filtered while hot thereafter by 16～18 ℃ of heating.Make reacting liquid temperature be reduced to 15 ℃ naturally again by 90 ℃.
Under 15 ℃ of temperature, leave standstill 24 hours after, at the uniform velocity reducing in the temperature course, stir once at every interval 0.5 hour, carries out crystallization.Then, till centrifuge dripping to dripless flows out in whizzer with material, make the wet type coarse crystal.Be that its pure water of 4.3 times injects the wet type coarse crystal then with weight, stirring and dissolving, the feed liquid after will dissolving again is heated to 60 ℃, stir after 55 minutes, filtered while hot also is cooled to room temperature with filtrate, leaves standstill 12 hours, separate out pure crystal, crystal is collected in vacuum filtration again.Under 75 ℃ of temperature, crystal to be dried in drying plant, be 2 hours time of drying, material was stirred at every interval in 15 minutes, and with its grinding.Carry out the crystal screening at last, crystal size is 40 orders, is the pale yellow powder shape.
The fusing point of finished product is 145～148 ℃ after testing, and weight is 5 kilograms.
Claims (4)
1, the preparation method of a kind of carboxyalkyl Lip river tannin comprises preparation cyclisation thing crude product and aftertreatment thereof, it is characterized in that:
11 preparation cyclisation thing crude products are first with aminocarboxylic acid, chlorinated carboxylic acid difference salify, revulcanization behind the aminocarboxylic acid salify, and acidified successively then, cyclization operation obtains cyclisation thing crude product;
12 crude product aftertreatments have filtration successively, cool off, leave standstill, crystallization, separation, dissolving, refining, dry, pulverize, screening and detect operation, make finished product at last;
In the 13 above-mentioned aminocarboxylic acid salify operations, with dissolving in 9.5～11 kilograms of sodium hydroxide input 64～66 premium on currency, under 15～20 ℃ of temperature, again 15～18 kilograms of aminocarboxylic acids are dropped into aqueous sodium hydroxide solution earlier, make the aminocarboxylic acid salts solution of pH value=6.8～7.2, standby;
In the 14 above-mentioned chlorinated carboxylic acid salify operations, will dissolve in 20～23 kilograms of chlorinated carboxylic acid input 58～62 premium on currency earlier, drop into 10～14 kilograms of yellow soda ash dissolvings again, make the chlorinated carboxylic acid salts solution of pH value=6.8～7.2, standby;
Revulcanization operation behind the 15 above-mentioned aminocarboxylic acid salifies under 7～12 ℃ of temperature, drops into standby aminocarboxylic acid salts solution with 12～16 liters of dithiocarbonic anhydride;
16 before entering acidizing process, adopt the mode of proprietary regulate process potential of hydrogen, after dropping into the chlorinated carboxylic acid salts solution, with above-mentioned two kinds of solution under 15～20 ℃ of temperature, carry out reaction in 5～6 hours, reacting liquid pH value=6.8～7.0, the temperature that input is prepared in advance by 455～465 gram sodium hydroxide and 455～465 ml waters in reaction solution is 10～15 ℃ a aqueous sodium hydroxide solution, stir after 15～25 minutes, left standstill 5～10 minutes, left standstill 10～14 hours conditioned reaction liquid pH value=8.5～8.9 again, behind conditioned reaction liquid pH value=6.8～7.2, enter acidizing process;
In the 17 above-mentioned acidizing process, under 15～20 ℃ of temperature, in the sulfuric acid or 37～41 liters of inputs of hydrochloric acid reaction solution with concentration 27～30%, regulate pH value=2～3, left standstill 3.5～4.5 hours;
In 18 above-mentioned cyclizations, the filtration operation, make reacting liquid temperature rise to 85～95 ℃, 1.8～2.2 hours ring-closure reaction time, filtered while hot thereafter by 15～20 ℃ of heating;
In the 19 above-mentioned refrigerating work procedures, make reacting liquid temperature be reduced to 15～20 ℃ naturally by 85～95 ℃;
110 above-mentionedly leave standstill, in the Crystallization Procedure, under 15～20 ℃ of temperature, leave standstill 24～28 hours after, at the uniform velocity reducing in the temperature course, stirred once in 0.5 hour at every interval, carries out crystallization;
In the 111 above-mentioned separation circuits, till centrifuge dripping to dripless flows out in whizzer with material, make the wet type coarse crystal;
In 112 above-mentioned dissolvings, the refining step, with weight is that its pure water of 4～5 times injects the wet type coarse crystal, stirring and dissolving, feed liquid after will dissolving again is heated to 50～70 ℃, stirs after 40～60 minutes, and filtered while hot also is cooled to room temperature with filtrate, left standstill 10～14 hours, separate out pure crystal, crystal is collected in vacuum filtration again;
In 113 above-mentioned dryings, the pulverizing process, under 60～80 ℃ of temperature, crystal is dried in drying plant, be 2～2.5 hours time of drying, and material was stirred at every interval in 10～15 minutes, and with its grinding;
In the 114 above-mentioned screening operations, the crystal sieve size is 40～60 orders.
2, the preparation method of carboxyalkyl as claimed in claim 1 Lip river tannin is characterized in that abovementioned alkyl is methyl, ethyl or propyl group.
3, the preparation method of carboxyalkyl as claimed in claim 1 Lip river tannin is characterized in that above-mentioned aminocarboxylic acid is Padil or alanine.
4, the preparation method of carboxyalkyl as claimed in claim 1 Lip river tannin is characterized in that above-mentioned chlorinated carboxylic acid is a Monochloro Acetic Acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03114078 CN1254468C (en) | 2003-03-28 | 2003-03-28 | Preparation method of carboxyalkyl lotanning |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03114078 CN1254468C (en) | 2003-03-28 | 2003-03-28 | Preparation method of carboxyalkyl lotanning |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1443760A CN1443760A (en) | 2003-09-24 |
| CN1254468C true CN1254468C (en) | 2006-05-03 |
Family
ID=27814773
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03114078 Expired - Lifetime CN1254468C (en) | 2003-03-28 | 2003-03-28 | Preparation method of carboxyalkyl lotanning |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1254468C (en) |
-
2003
- 2003-03-28 CN CN 03114078 patent/CN1254468C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CN1443760A (en) | 2003-09-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6218574B1 (en) | Process for purifying long-chain dicarboxylic acid | |
| JPH0390054A (en) | Preparation of cyclic amino acid and its interme- diate | |
| WO2021022788A1 (en) | Composition of 5-fluorouracil and refining method therefor | |
| CN110452255A (en) | Crystal form of Ceftriaxone Sodium and preparation method thereof | |
| CN102351847B (en) | Industrial method for refining esomeprazole sodium salt | |
| CN1254468C (en) | Preparation method of carboxyalkyl lotanning | |
| CN102924311A (en) | L-ornithine-L-aspartate preparation method | |
| CN102329276B (en) | Method for recovering valsartan mother liquid | |
| CN106749226A (en) | A kind of preparation method of avatrombopag maleates crystal formation C | |
| CN102321040B (en) | Method for preparing linezolid intermediate and linezolid | |
| RU96121255A (en) | IMPROVED METHOD FOR PRODUCING 6,9-BIS - [(2-AMINOETHYL) -AMINO] BENZO [G] Isoquinoline-5,10-DIONE AND ITS DIMALEATE SALTS | |
| CN101200451A (en) | Method for preparing hydrochloride urapidil | |
| CN1490297A (en) | Preparation of dextroilbuprofen | |
| US2542869A (en) | N-pyridoxyl-amino acids and process of preparing the same | |
| CN115745897B (en) | Clozapine recrystallization method | |
| CN108864090B (en) | A kind of preparation method of Eliquis N-1 crystal | |
| CN102731340A (en) | Preparation method of demethyl aureomycin hydrochloride | |
| CN106810458B (en) | A method of it splitting DL-2- aminopropanol and prepares L-2- aminopropanol | |
| JPH0859517A (en) | Optical resolution agent and production of optically active tetrahydrofuran-carboxylic acid using the same | |
| CN103274998B (en) | Preparation method of flupirtine maleate | |
| CN102206185B (en) | Process for refining bendazac lysine and analogs thereof | |
| CN117510444B (en) | Refining process of furosemide | |
| CN102976980B (en) | Probenecid purification method | |
| CN114634408B (en) | Purification method of ultraviolet light absorber oxybenzone | |
| CN115850056B (en) | Preparation method of ibuprofen L-lysine salt |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: XILONG CHEMICAL CO., LTD. Free format text: FORMER OWNER: SHANTOU XILONG CHEMICAL FACTORY Effective date: 20090918 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20090918 Address after: Guangdong city of Shantou province Chaoshan Road West Long Street 1-3 Patentee after: XILONG CHEMICAL Co.,Ltd. Address before: Guangdong city of Shantou province Chaoshan Road West Long Street 1-3 Patentee before: Xilong Chemical Plant, Shantou City |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20151225 Address after: 528100 Guangdong Province, Foshan City Sanshui Industrial Park District Tang Hing Road No. 29 Patentee after: FOSHAN XILONG CHEMICAL CO.,LTD. Address before: 515064 Guangdong city of Shantou province Chaoshan Road West Long Street No. 1-3 Patentee before: XILONG CHEMICAL Co.,Ltd. |
|
| CX01 | Expiry of patent term |
Granted publication date: 20060503 |
|
| CX01 | Expiry of patent term |