CN110229092A - A kind of method of efficient production epiphysin - Google Patents
A kind of method of efficient production epiphysin Download PDFInfo
- Publication number
- CN110229092A CN110229092A CN201910475744.1A CN201910475744A CN110229092A CN 110229092 A CN110229092 A CN 110229092A CN 201910475744 A CN201910475744 A CN 201910475744A CN 110229092 A CN110229092 A CN 110229092A
- Authority
- CN
- China
- Prior art keywords
- compound
- epiphysin
- methoxy
- indole
- proportion
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 34
- DWAQDRSOVMLGRQ-UHFFFAOYSA-N 5-methoxyindole Chemical compound COC1=CC=C2NC=CC2=C1 DWAQDRSOVMLGRQ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 238000006722 reduction reaction Methods 0.000 claims abstract description 19
- 239000002994 raw material Substances 0.000 claims abstract description 16
- 230000009467 reduction Effects 0.000 claims abstract description 14
- 239000012280 lithium aluminium hydride Substances 0.000 claims abstract description 12
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 9
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000000908 ammonium hydroxide Substances 0.000 claims abstract description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 5
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 claims abstract description 3
- 229940127113 compound 57 Drugs 0.000 claims abstract description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 6
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 claims description 4
- -1 sodium aluminum hydride Chemical compound 0.000 claims description 4
- YCNZFPXXIWEFCF-UHFFFAOYSA-N alumane;sodium Chemical class [Na].[AlH3] YCNZFPXXIWEFCF-UHFFFAOYSA-N 0.000 claims description 3
- 230000008859 change Effects 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 238000005649 metathesis reaction Methods 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- 229910001148 Al-Li alloy Inorganic materials 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- FCVHBUFELUXTLR-UHFFFAOYSA-N [Li].[AlH3] Chemical compound [Li].[AlH3] FCVHBUFELUXTLR-UHFFFAOYSA-N 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 238000011084 recovery Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 230000028327 secretion Effects 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229960000935 dehydrated alcohol Drugs 0.000 description 3
- 206010062767 Hypophysitis Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 2
- 229910020828 NaAlH4 Inorganic materials 0.000 description 2
- 238000004176 ammonification Methods 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- 229960003987 melatonin Drugs 0.000 description 2
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000004560 pineal gland Anatomy 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 241000195493 Cryptophyta Species 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940088623 biologically active substance Drugs 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002561 ketenes Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000003452 oxalyl group Chemical group *C(=O)C(*)=O 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a kind of methods of efficiently production epiphysin, are related to epiphysin synthesis technical field, purity recovery rate is lower during producing production and produces higher cost to solve the problem of epiphysin in the prior art.Including being 100% by raw material proportion of 5- methoxy-Indole, phosgene proportion is the 98% of raw material, ammonium hydroxide proportion is generate compound 57%, lithium aluminium hydride reduction proportion is generate compound 80%, 5- methoxy-Indole (1) is raw material, and phosgene reaction dissolvent is added, make 5- methoxy-Indole oxalyl group, compound (2) are generated to react, the compound (2) for producing generation is stood, later ammonium hydroxide solvent mix with it according to doses and generates compound (3), after compound (3) generate, a kind of lithium aluminium hydride reduction reagent is added again, it is set to generate reduction reaction, to generate compound (4).
Description
Technical field
The present invention relates to epiphysin synthesis technical field, specially a kind of method of efficiently production epiphysin.
Background technique
Epiphysin is a kind of amine bormones generated by the pineal body of mammal and the mankind, can make a kind of generation black
The cell of element is shinny, thus is named as epiphysin.It is present in from algae to the mankind etc. in numerous biologies, and contents level is with daily
Time change, epiphysin is the biologically active substance being found earliest in pineal body, mammal be in it is black
When in the dark, melatonin secretion activity is reinforced immediately；Then stop secretion when turning in bright environment.The rhythm and pace of moving things of melatonin secretion,
It can be measured from urine with the variation of light.Other factors such as sleep, diet, the state of mind and stress situation also have one
Fixing is rung.Injection epiphysin can inhibit the secretion of promoting sexual gland hormone in hypothalamus, but also observe that epiphysin can be acted on directly
In hypophysis.Therefore epiphysin can inhibit the secretion of promoting sexual gland hormone by hypothalamus and (or) hypophysis.In addition in ovary
Also it has been found that there is the receptor of epiphysin, illustrate that this is also the action site of epiphysin.
But existing epiphysin purity recovery rate during producing production is lower, and produces higher cost；Cause
This, is unsatisfactory for existing demand, and to this, we have proposed a kind of methods of efficiently production epiphysin.
Summary of the invention
The purpose of the present invention is to provide a kind of methods of efficiently production epiphysin, to solve to propose in above-mentioned background technique
Epiphysin during producing production purity recovery rate it is lower, and the problem of produce higher cost.
To achieve the above object, the invention provides the following technical scheme: a kind of method of efficiently production epiphysin, with material
Quantity is 100% than meter, including by raw material proportion of 5- methoxy-Indole, and phosgene proportion is the 98% of raw material,
Ammonium hydroxide proportion is generate compound 57%, and lithium aluminium hydride reduction proportion is generate compound 80%.
Preferably, include the following steps:
Step 1: 5- methoxy-Indole (1) is raw material, and phosgene reaction dissolvent is added, and makes 5- methoxy-Indole oxalyl
Base generates compound (2) to react；
Step 2: will produce generation compound (2) stand, later by ammonium hydroxide solvent according to doses and its into
Row mixing generates compound (3)；
Step 3: after compound (3) generate, then adding a kind of lithium aluminium hydride reduction reagent, it is made to generate reduction reaction, thus
It generates compound (4)；
Step 4: a certain amount of acetic anhydride reagent is added in the compound (5) of generation as last reaction dissolvent, instead
Compound (6), that is, epiphysin should be generated.
Preferably, in the step 1, need to be added a certain amount of tetrahydrofuran solvent conduct in 5- methoxy-Indole
Basic reaction solvent.
Preferably, in the step 3, lithium aluminium hydride reduction is produced by sodium aluminum hydride, using the synthesizing hydrogenated aluminium sodium of high temperature and pressure,
Then metathesis reaction is carried out with lithium chloride.
Compared with prior art, the beneficial effects of the present invention are:
1, the present invention passes through oxalyl group by being raw material as the raw material of producing of epiphysin using 5- methoxy-Indole later
Change, ammonification, reduction and dealing with alcohol carry out it is whole produce reaction, the short operation of entire operation process period is simple, and finally
The total recovery rate of epiphysin is higher；
2, the present invention is producing reaction by the way that tetrahydrofuran solvent to be added in 5- methoxy-Indole as reaction dissolvent
In need to be added a certain amount of dehydrated alcohol as reaction dissolvent, but dehydrated alcohol produces higher cost, passes through tetrahydrofuran
Solvent substitutes dehydrated alcohol as new reaction dissolvent, to maximize degree guarantee epiphysin extraction efficiency while
Reduction produce cost.
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical scheme in the embodiment of the invention is clearly and completely described,
Obviously, described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.
A kind of embodiment provided by the invention: a method of efficiently production epiphysin, in terms of material quantity ratio, including with
5- methoxy-Indole is that raw material proportion is 100%, and phosgene proportion is the 98% of raw material, ammonium hydroxide proportion
It is the 57% of generation compound, lithium aluminium hydride reduction proportion is generate compound 80%.
Further, include the following steps:
Step 1: 5- methoxy-Indole (1) is raw material, and phosgene reaction dissolvent is added, and makes 5- methoxy-Indole oxalyl
Base generates compound (2) to react；
Step 2: will produce generation compound (2) stand, later by ammonium hydroxide solvent according to doses and its into
Row mixing generates compound (3), and the raw material that goes out for producing it generates ammonification；
Step 3: after compound (3) generate, then adding a kind of lithium aluminium hydride reduction reagent, it is made to generate reduction reaction, thus
It generates compound (4)；
Step 4: a certain amount of acetic anhydride reagent is added in the compound (5) of generation as last reaction dissolvent, second
Cracking can obtain ketenes to acid at high temperature, then absorb to obtain acetic anhydride with acetic acid again, and when purification is removed by the way that benzene azeotropic distillation is added
It removes acetic acid or high purity acetic acid acid anhydride can be made by high effect of reducing pressure rectifying, reaction generates compound (6), that is, epiphysin.
Further, in step 1, based in 5- methoxy-Indole needing that a certain amount of tetrahydrofuran solvent is added
Cost is produced in reaction dissolvent, reduction.
Further, in step 3, lithium aluminium hydride reduction is produced by sodium aluminum hydride, in this way can be with save the cost, using high temperature and pressure
Synthesizing hydrogenated aluminium sodium, then with lithium chloride carry out metathesis reaction Na+Al+2H2 → NaAlH4, NaAlH4+LiCl-Et2O →
LiAlH4+NaC。
Working principle: in use, needing that a certain amount of tetrahydrofuran solvent conduct is added first in 5- methoxy-Indole
Later using 5- methoxy-Indole as raw material, and phosgene reaction dissolvent is added in basic reaction solvent, keeps 5- methoxy-Indole careless
Be acylated, thus react generate compound (2), will produce generation compound (2) stand, later by ammonium hydroxide solvent according to
Doses, which mix with it, generates compound (3), after compound (3) generate, then adds a kind of lithium aluminium hydride reduction reagent, makes
It generates reduction reaction, to generate compound (4), a certain amount of acetic anhydride reagent is added in the compound (5) of generation and makees
For last reaction dissolvent, reaction generates compound (6), that is, epiphysin.
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case where without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Benefit requires rather than above description limits, it is intended that all by what is fallen within the meaning and scope of the equivalent elements of the claims
Variation is included within the present invention.Any reference signs in the claims should not be construed as limiting the involved claims.
Claims (4)
1. a kind of method of efficiently production epiphysin, which is characterized in that be in terms of material quantity ratio, including with 5- methoxy-Indole
Raw material proportion is 100%, and phosgene proportion is the 98% of raw material, and ammonium hydroxide proportion is to generate compound
57%, lithium aluminium hydride reduction proportion is generate compound 80%.
2. a kind of method of efficiently production epiphysin according to claim 1, which comprises the steps of:
Step 1: 5- methoxy-Indole (1) is raw material, and phosgene reaction dissolvent is added, and makes 5- methoxy-Indole oxalyl group,
Compound (2) are generated to react；
Step 2: the compound (2) for producing generation is stood, later mixes ammonium hydroxide solvent with it according to doses
Symphysis is at compound (3)；
Step 3: after compound (3) generate, then adding a kind of lithium aluminium hydride reduction reagent, so that it is generated reduction reaction, to generate
Compound (4)；
Step 4: a certain amount of acetic anhydride reagent is added in the compound (5) of generation as last reaction dissolvent, reaction life
At compound (6), that is, epiphysin.
3. a kind of method of efficiently production epiphysin according to claim 2, it is characterised in that: in the step 1,
Need to be added a certain amount of tetrahydrofuran solvent in 5- methoxy-Indole as basic reaction dissolvent.
4. a kind of method of efficiently production epiphysin according to claim 2, it is characterised in that: in the step 3, hydrogen
Change aluminium lithium to be produced by sodium aluminum hydride, using the synthesizing hydrogenated aluminium sodium of high temperature and pressure, then carries out metathesis reaction with lithium chloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910475744.1A CN110229092A (en) | 2019-06-03 | 2019-06-03 | A kind of method of efficient production epiphysin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910475744.1A CN110229092A (en) | 2019-06-03 | 2019-06-03 | A kind of method of efficient production epiphysin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110229092A true CN110229092A (en) | 2019-09-13 |
Family
ID=67859172
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910475744.1A Pending CN110229092A (en) | 2019-06-03 | 2019-06-03 | A kind of method of efficient production epiphysin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110229092A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113072479A (en) * | 2021-03-26 | 2021-07-06 | 罗田县新普生药业有限公司 | Method for extracting melatonin from melatonin crystallization mother liquor |
-
2019
- 2019-06-03 CN CN201910475744.1A patent/CN110229092A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113072479A (en) * | 2021-03-26 | 2021-07-06 | 罗田县新普生药业有限公司 | Method for extracting melatonin from melatonin crystallization mother liquor |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105780049B (en) | A kind of Trace Amounts of Platinum modification efficient liberation of hydrogen catalyst of molybdenum sulfide and preparation method thereof | |
| Soler et al. | Hydrogen generation by aluminum corrosion in seawater promoted by suspensions of aluminum hydroxide | |
| CN102925492A (en) | Method for restoring carbon dioxide to produce methane and acetic acid by utilizing biological electrochemical system | |
| CN109267092A (en) | A kind of molybdenum disulfide composite material and preparation method and purposes | |
| EA201100571A1 (en) | RECEIVING SILICON FOR SOLAR BATTERIES FROM SILICON DIOXIDE | |
| BR112014021850B1 (en) | METHOD FOR RECOVERING RUTENIUM FROM ALUMINUM OXIDE CATALYST WASTE CHARGED WITH RUTHIUM | |
| RU2013117459A (en) | SIMULTANEOUS HYDROLYSIS AND HYDROGENIZATION OF CELLULOSE | |
| CN103603014B (en) | Electrolytic aluminum production method taking elpasolite as supplemental system | |
| CN1615270A (en) | Aqueous borohydride compositions | |
| CN104372030A (en) | Method for coproducing hydrogen gas and methane by sludge-kitchen waste mixed fermentation | |
| CN110229092A (en) | A kind of method of efficient production epiphysin | |
| EP3569739A1 (en) | Method of producing ammonium persulfate | |
| JP2020005599A (en) | Protein production system and protein production method | |
| CN108796530B (en) | Novel method for electrochemically synthesizing ammonia | |
| CN101967567A (en) | Method for preparing metal vanadium | |
| CN101746727B (en) | Method for preparing LiBH4 xNH3 compounds | |
| CN101139086A (en) | Method and equipment for generating hydrogen by using magnesium metal waste | |
| ATE501107T1 (en) | METHOD FOR CONVERTING LEVULIC ACID TO PENTANIC ACID | |
| CN102557869A (en) | Method for preparing methanol fuel by utilizing biomass charcoal | |
| CN109912154A (en) | Method for efficiently producing hydrogen and inhibiting methane production in a microbial electrolytic cell | |
| CN102423623A (en) | Multifunctional raw material gas purifying agent and preparation and application methods thereof | |
| CN107142285A (en) | Method for producing biogas based on carbon electrode electrolysis coupling anaerobic fermentation | |
| CN108315357A (en) | The method and system of combustible are coupled using regenerative resource and biomass | |
| CN109811362A (en) | A method for photoelectric catalytic oxidation of xylose using indium sulfide/nickel-cobalt-aluminum hydrotalcite composite film | |
| CN107597116A (en) | A kind of method that 1,4 pentanediols are prepared by copper-based catalysts direct hydrogenation levulic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190913 |