CN106380430A - Synthetic method of 3-(triphenylmethylthio)propionic acid - Google Patents
Synthetic method of 3-(triphenylmethylthio)propionic acid Download PDFInfo
- Publication number
- CN106380430A CN106380430A CN201610801304.7A CN201610801304A CN106380430A CN 106380430 A CN106380430 A CN 106380430A CN 201610801304 A CN201610801304 A CN 201610801304A CN 106380430 A CN106380430 A CN 106380430A
- Authority
- CN
- China
- Prior art keywords
- acid
- synthetic method
- reaction
- triphenylmethylthio
- dissolved
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
Abstract
The invention relates to a synthetic method of 3-(triphenylmethylthio)propionic acid. The technical problems of high cost, participation of a toxic raw material in a reaction, and adverseness to massive production of present synthetic methods are mainly solved. The synthetic method of 3-(triphenylmethylthio)propionic acid comprises the following steps: 1, dissolving 3-thiopropionic acid in acetate acid gracial at room temperature; 2, dissolving triphenylmethanol in tetrahydrofuran at room temperature; 3, adding the obtained tetrahydrofuran solution of triphenylmethanol to the acetate acid gracial solution of 3-thiopropionic acid in step 1; 4, dropwise adding concentrated sulfuric acid; 5, carrying out a heat insulation reaction for 3-5 h; and 6, filtering a solid obtained after the reaction, dissolving the filtered solid in dimethyl formamide, adding water, and crystallizing to obtain fine 3-(triphenylmethylthio)propionic acid. The synthetic method provided by the invention is a method for large-scale production of 3-(triphenylmethylthio)propionic acid.
Description
Technical field
The present invention relates to a kind of synthetic method of 3- (three benzene methyl sulfonium) propanoic acid.
Background technology
Existing preparation 3- (three benzene methyl sulfonium) propanoic acid method is generally：The first step, under room temperature, 3- thiohydracrylic acid is dissolved in ice
Acetic acid, adds trityl chloride.Second step, adds boron trifluoride diethyl etherate.3rd step is incubated 45 DEG C and reacts 3 hours.4th step, body
System adds 10 times amount sodium acetate aqueous solutions to crystallize to obtain crude product.5th step, crude product heats recrystallization with 20 times of methanol, obtains fine work.This
Kind method synthesis condition is harsher, and the very unstable price of raw material boron trifluoride diethyl etherate is higher, and recrystallizing methanol loss is unfavorable greatly
In environmental protection, also it is unfavorable for producing in a large number.
Content of the invention
The present invention relates to a kind of synthetic method of 3- (three benzene methyl sulfonium) propanoic acid.Mainly solve existing synthetic method cost
Higher, and need toxic raw materials to participate in reaction, it is unfavorable for the technical problem producing in a large number.
Technical scheme：The present invention relates to a kind of synthetic method of 3- (three benzene methyl sulfonium) propanoic acid, it is characterized in that
Comprise the following steps：One, under room temperature, 3- thiohydracrylic acid is dissolved in glacial acetic acid.Two, under room temperature, Trt-OH is dissolved in THF.Three, by Trt-
The THF solution of OH is added in step one mixed solution.Four, Deca concentrated sulphuric acid.Five, insulation reaction 3-5 hour.Six, reaction is produced
Raw solid is dissolved in DMF after filtering.Seven, system adds water and crystallizes to obtain fine work.
Described first step reaction, under room temperature, 3- thiohydracrylic acid is dissolved in glacial acetic acid, the glacial acetic acid of prioritizing selection 3 times amount（3- sulfur
Base propanoic acid:Glacial acetic acid m:v =1:3）.
Described second step reaction, Trt-OH (Trt-OH under room temperature:3-MPA mol:mol 1:1) it is dissolved in THF, preferential choosing
Select the THF (Trt-OH of 3 times amount:THF m:v =1:3).
Told three-step reaction, the THF solution of Trt-OH is added in step one.
Described four-step reaction, Deca concentrated sulphuric acid, the amount of concentrated sulphuric acid is 0.18-0.2mol times of (H of 3- thiohydracrylic acid2SO4:
3-MPA mol:mol 0.18-0.2 :1), 0.18mol times of prioritizing selection.
Described 5th step reaction, insulation reaction 4 hours.
Described six-step process, reaction produces the DMF being dissolved in doubling dose after solid filters（Solid: DMF m:v =1:2）
In.
Described 7th step is reacted, plus 5 times of volume water crystallizations of system obtain fine work.
In the present invention, some conventional abbreviations have following meanings：
Trt-OH：Tritanol.
THF：Oxolane
DMF：Dimethylformamide
3-MPA ：3- thiohydracrylic acid.
Beneficial effects of the present invention：The cost of material of the present invention is relatively low, and all very stable, does not have special storage bar
Part.Do not need in production process to use boron trifluoride diethyl etherate, and whole production process solvent for use amount is smaller, is conducive to ring
Protect.
Brief description
Fig. 1 is product infared spectrum of the present invention.
Fig. 2 is product nuclear magnetic spectrum of the present invention.
Specific embodiment
Referring to example, the present invention is described in further detail, but the present invention does not limit and these instantiations.
Embodiment 1
A. at room temperature by 100g 3- thiohydracrylic acid（106.14 942.15nmol）It is dissolved in 300ml glacial acetic acid,
B. at room temperature by 245.27g Trt-OH（ 260.33 942.15nmol）It is dissolved in 736.79mlTHF,
C. a step products are slowly added in b step product,
D.28 DEG C -30 DEG C of Deca 16.62g concentrated sulphuric acids（ 98 169.587nmol）,
E. insulation reaction 4 hours,
F. reaction produces solid and filters to obtain crude product 360g, and solid is dissolved in 720ml DMF,
G. plus system 5 times amount water crystallization, filtering drying obtains fine work 295.5g yield 90%.Just confirming structure through infrared, nuclear-magnetism
Really, Fig. 1, Fig. 2 are seen.
Embodiment 2
A. at room temperature by 100g 3- thiohydracrylic acid（106.14 942.15nmol）It is dissolved in 300ml glacial acetic acid,
B. at room temperature by 294.32g Trt-OH（ 260.33 1130.58nmol）It is dissolved in 736.79mlTHF,
C. a step products are slowly added in b step product,
D.28 DEG C -30 DEG C of Deca 16.62g concentrated sulphuric acids（ 98 169.587nmol）,
E. insulation reaction 5 hours,
F. reaction produces solid and filters to obtain crude product 380g, and solid is dissolved in 760ml DMF,
G. plus system 5 times amount water crystallization, filtering drying obtains fine work 292.2g yield 89%.Just confirming structure through infrared, nuclear-magnetism
Really, Fig. 1, Fig. 2 are seen.
Embodiment 3
A. at room temperature by 100g 3- thiohydracrylic acid（106.14 942.15nmol）It is dissolved in 300ml glacial acetic acid,
B. at room temperature by 245.27g Trt-OH（ 260.33 942.15nmol）It is dissolved in 736.79mlTHF,
C. a step products are slowly added in b step product,
D.28 DEG C -30 DEG C of Deca 18.47g concentrated sulphuric acids（ 98 188.43nmol）,
E. insulation reaction 3 hours,
F. reaction produces solid and filters to obtain crude product 350g, and solid is dissolved in 700ml DMF,
G. plus system 5 times amount water crystallization, filtering drying obtains fine work 262.6g yield 80%.Just confirming structure through infrared, nuclear-magnetism
Really, Fig. 1, Fig. 2 are seen.
Embodiment 4
A. at room temperature by 100g 3- thiohydracrylic acid（106.14 942.15nmol）It is dissolved in 300ml glacial acetic acid,
B. at room temperature by 245.27g Trt-OH（ 260.33 942.15nmol）It is dissolved in 736.79mlTHF,
C. a step products are slowly added in b step product,
D. 20 DEG C of Deca 16.62g concentrated sulphuric acids（ 98 169.587nmol）,
E. room temperature reaction 4 hours,
F. reaction produces solid and filters to obtain crude product 300g, and solid is dissolved in 720ml DMF,
G. plus system 5 times amount water crystallization, filtering drying obtains fine work 164.2g yield 50%.Just confirming structure through infrared, nuclear-magnetism
Really, Fig. 1, Fig. 2 are seen.
Claims (6)
1. a kind of synthetic method of 3- (three benzene methyl sulfonium) propanoic acid, is characterized in that comprising the following steps：One, 3- sulfenyl third under room temperature
Acid is dissolved in glacial acetic acid；Two, under room temperature, tritanol. is dissolved in oxolane；Three, the tetrahydrofuran solution of tritanol. is added
To in step one mixed solution；Four, Deca concentrated sulphuric acid；Five, insulation reaction 3-5 hour；Six, reaction produces after solid filters and is dissolved in
In dimethylformamide, add water and crystallize to obtain fine work.
2. the synthetic method of a kind of 3- (three benzene methyl sulfonium) propanoic acid according to claim 1, the first step described in its feature is anti-
Should, 3- thiohydracrylic acid:The quality of glacial acetic acid and volume ratio=1:3.
3. the synthetic method of a kind of 3- (three benzene methyl sulfonium) propanoic acid according to claim 1, second step described in its feature is anti-
Should, tritanol. and 3- thiohydracrylic acid mol ratio=1:1；Tritanol. and oxolane quality and volume ratio=1:3.
4. a kind of synthetic method of 3- (three benzene methyl sulfonium) propanoic acid according to claim 1, is characterized in that described 4th step
Reaction, 28 DEG C -30 DEG C Deca concentrated sulphuric acids；The amount of concentrated sulphuric acid is 0.18-0.2mol times of 3- thiohydracrylic acid.
5. a kind of synthetic method of 3- (three benzene methyl sulfonium) propanoic acid according to claim 1, is characterized in that described 5th step
Reaction, insulation reaction 3-5 hour.
6. a kind of synthetic method of 3- (three benzene methyl sulfonium) propanoic acid according to claim 1, is characterized in that described 6th step
Reaction, solid and dimethylformamide quality and volume ratio=1:2, plus 5 times of volume of water of system.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610801304.7A CN106380430A (en) | 2016-09-05 | 2016-09-05 | Synthetic method of 3-(triphenylmethylthio)propionic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610801304.7A CN106380430A (en) | 2016-09-05 | 2016-09-05 | Synthetic method of 3-(triphenylmethylthio)propionic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106380430A true CN106380430A (en) | 2017-02-08 |
Family
ID=57937972
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610801304.7A Pending CN106380430A (en) | 2016-09-05 | 2016-09-05 | Synthetic method of 3-(triphenylmethylthio)propionic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106380430A (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0013261A1 (en) * | 1978-12-21 | 1980-07-09 | Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. | Guaiacol esters of alpha- and beta-mercaptopropionylalanine and alpha- and beta-mercaptopropionylglycine, process for their preparation and pharmaceutical compositions containing same |
| US5011975A (en) * | 1988-03-04 | 1991-04-30 | Nippon Miktron Limited | Novel (trans 1-propenyl)disulfide derivative and process for preparing the same |
| WO1995020404A1 (en) * | 1994-01-31 | 1995-08-03 | University Of Medicine & Dentistry Of New Jersey | Triplex-forming paired-ion oligonucleotides and methods for preparing and using same |
| WO1999020649A1 (en) * | 1997-10-22 | 1999-04-29 | Merck Patent Gmbh | Spacer peptides and membranes containing same |
| WO2002053624A1 (en) * | 2001-01-05 | 2002-07-11 | Kings College London | Crosslinked disulphide containing polymers for drug delivery |
| US20030220245A1 (en) * | 2000-06-02 | 2003-11-27 | Hubbell Jeffrey A | Conjugate addition reactions for the controlled delivery of pharmaceutical active compounds |
| US20040082079A1 (en) * | 2001-02-05 | 2004-04-29 | Ralf Besenbruch | Low affinity screening method |
| JP2013048833A (en) * | 2011-08-31 | 2013-03-14 | Terumo Corp | Medical instrument with antibacterial surface |
-
2016
- 2016-09-05 CN CN201610801304.7A patent/CN106380430A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0013261A1 (en) * | 1978-12-21 | 1980-07-09 | Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. | Guaiacol esters of alpha- and beta-mercaptopropionylalanine and alpha- and beta-mercaptopropionylglycine, process for their preparation and pharmaceutical compositions containing same |
| US5011975A (en) * | 1988-03-04 | 1991-04-30 | Nippon Miktron Limited | Novel (trans 1-propenyl)disulfide derivative and process for preparing the same |
| WO1995020404A1 (en) * | 1994-01-31 | 1995-08-03 | University Of Medicine & Dentistry Of New Jersey | Triplex-forming paired-ion oligonucleotides and methods for preparing and using same |
| WO1999020649A1 (en) * | 1997-10-22 | 1999-04-29 | Merck Patent Gmbh | Spacer peptides and membranes containing same |
| US20030220245A1 (en) * | 2000-06-02 | 2003-11-27 | Hubbell Jeffrey A | Conjugate addition reactions for the controlled delivery of pharmaceutical active compounds |
| WO2002053624A1 (en) * | 2001-01-05 | 2002-07-11 | Kings College London | Crosslinked disulphide containing polymers for drug delivery |
| US20040082079A1 (en) * | 2001-02-05 | 2004-04-29 | Ralf Besenbruch | Low affinity screening method |
| JP2013048833A (en) * | 2011-08-31 | 2013-03-14 | Terumo Corp | Medical instrument with antibacterial surface |
Non-Patent Citations (2)
| Title |
|---|
| PETER N. CONESKI 等: "Synthesis of nitric oxide-releasing polyurethanes with S-nitrosothiol-containing hard and soft segments", 《POLYM. CHEM.》 * |
| RONALD G. SCHOENMAKERS 等: "The effect of the linker on the hydrolysis rate of drug-linked ester bonds", 《JOURNAL OF CONTROLLED RELEASE》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108610324B (en) | Preparation method of vinyl sulfate | |
| CN106279097B (en) | A kind of preparation method of acrylic -1,3- sultones | |
| CN110862323A (en) | Synthesis method of diaminodiphenylethane compound | |
| CN103864802A (en) | Preparation method of high-purity asenapine maleate | |
| CN103012437B (en) | The preparation method of antibacterial drugs cefoxitin acid | |
| CN102617335B (en) | Process for synthesizing p-tert-butylbenzoic acid | |
| CN106892823A (en) | The method for synthesizing the chloro- 3,5- dinitro-p-trifluorotoluenes of 2,4- bis- in microreactor | |
| CN110627754B (en) | Method for preparing 2-oxo-2-furyl acetic acid by using continuous flow microchannel reactor | |
| CN102199073A (en) | Method for preparing 4,4'-dihydroxydiphenylmethane | |
| CN106380430A (en) | Synthetic method of 3-(triphenylmethylthio)propionic acid | |
| CN104892389B (en) | Technique for preparing oxalic acid by performing continuous reaction rectification hydrolysis on dimethyl oxalate | |
| CN110922373A (en) | Synthesis method of methyl platinolate | |
| CN106748770A (en) | A kind of simple and convenient process for preparing of felbinac | |
| CN113861034A (en) | Preparation method of 2-fluoro-3-nitrobenzoic acid | |
| CN107311950A (en) | A kind of preparation method of cyanuric acid lanthanum | |
| CN103613536B (en) | The industrialized process for preparing of 2-pyridine carboxylic acid copper | |
| CN112778094A (en) | Preparation process of high-purity tetrabromobisphenol A | |
| CN104628526B (en) | A kind of preparation method of adamantane triol | |
| CN110143861A (en) | A kind of preparation method of brufen | |
| CN105461718A (en) | 5-Bromo-7-azaindole synthesis process | |
| CN110759840A (en) | Synthesis method of 1, 1-dibromo-2, 2-bis (chloromethyl) cyclopropane | |
| CN106866378B (en) | Synthetic process of phloroglucinol | |
| CN108341770A (en) | A kind of preparation method of Sorafenib compound | |
| CN102453068B (en) | Improvement preparation method for oxabolone cipionate | |
| CN112142635B (en) | Preparation method of olefine acid impurity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170208 |