CN109320476A - A kind of preparation method of Norleucyl base benzenethiol - Google Patents
A kind of preparation method of Norleucyl base benzenethiol Download PDFInfo
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- CN109320476A CN109320476A CN201710637519.4A CN201710637519A CN109320476A CN 109320476 A CN109320476 A CN 109320476A CN 201710637519 A CN201710637519 A CN 201710637519A CN 109320476 A CN109320476 A CN 109320476A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/104—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/108—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
- C07C319/06—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols from sulfides, hydropolysulfides or polysulfides
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- 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
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of preparation methods of compound Norleucyl base benzenethiol shown in formula (I).Using corresponding Dimethyl sulfide compound as raw material, chlorination reaction first is carried out with chlorination reagent such as chlorine, chlorosulfuric acid or phosphorus pentachloride, then obtain target product through alcoholysis reaction and purification process.
Description
Technical field
The present invention relates to a kind of preparation methods of compound Norleucyl base benzenethiol shown in formula (I), especially 2- first
The preparation method of base -2- (4- morpholinyl) -1- (4- mercaptophenyl) -1- acetone.
Background technique
Alpha-amido phenyl isobutyl ketone compound is a kind of effective UV photoinitiator, such as 2- methyl -2- (4- morpholine
Base) -1- [4- (methyl mercapto) phenyl] -1- acetone in UV-curing technology in ink formulations, especially printing ink,
Solder mask and photoresist.But part is had after photocuring, ink film forming is not remained in by the small molecule compound of photodegradation
In, it is readily migrate into film surface and forms pollution, or extracted by solvent or contactant and contactant is caused to be contaminated；And in photoetching
In glue application, residual small-molecule substance can volatilize or distil in hot procedure and comes out, encounter the cooler wall of heating furnace and
It is condensed into powder again, is used for a long time and occurs accumulate, disperse, falling situation, machined object is caused to pollute, reduces yield rate,
Also lack effective solution method in the industry.
And compound similar with its Norleucyl base thiophenols as shown in formula I, such as 2- methyl -2-
(4- morpholinyl) -1- (4- mercaptophenyl) -1- acetone is the molecule with sulfydryl, and research finds this sulfydryl easily and double bond compound
Addition reaction occurs, entire photoinitiator molecules are connected on acrylate monomer or oligomer to a side for becoming them
Chain finally becomes crosslinked polymeric a part, so that its migration and volatility is effectively reduced, therefore in Light Curing
It can be used for manufacturing the non-migratory ink of food packaging applications and the low volatilization photoresist of display industry.
Method that there are mainly three types of current synthesis 2- methyl -2- (4- morpholinyl) -1- (4- mercaptophenyl) -1- acetone, the
One is Ciba-Geigy house journal EP0088050, with 2- methyl -2- (4- morpholinyl) -1- (4- chlorphenyl) -1- acetone with
Vulcanized sodium reaction, obtains target product.But in reaction process, it is easy to generate 2- methyl -2- (4- morpholinyl) -1- (4- chlorobenzene
Base) -1- acetone thioetherification by-product, influence yield, and due to using vulcanized sodium, thus the smell problem in reaction process and
Toxicity problem, and the processing problem of the waste water containing vulcanized sodium all become the industrialized obstacle of this method.
Second method is patent CN2010102332145, is mentioned with 2- methyl -2- (4- morpholinyl) -1- (4- chlorobenzene
Base) -1- acetone and rosickyite base sodium react in N-Methyl pyrrolidone and obtain target product, while by-product is dipropyl sulphur
Ether.The main problem of this method is by-product dipropyl thioether, and toxicity is strong, and this method fails to obtain the experiment card of the present inventor
It is real.
The third method is that patent JP2012007070 and patent JP2012007071 are disclosed, with 2- methyl -2- (4- morpholine
Base) -1- (4- methyl mercapto phenyl) -1- acetone be raw material, with MCPBA (m-chloro-benzoic acid peroxide) and trifluoracetic acid or trifluoro vinegar
Acid anhydrides conditioned response generates target product.The main problem of this method is that the use risk of peroxide is big, and trifluoracetic acid is not
But price, corrosivity is also big, and fluoride waste is difficult to handle.
So existing preparation method all exists or reagent toxicity is big or by-product toxicity is big, waste water is difficult etc.
Disadvantage.
Summary of the invention
Research finds a kind of preparation method of Norleucyl base thiophenols shown in formula I, reaction equation:
Wherein
R1, R2It is C1-C4 alkyl each independently, or by R5O、R5R6The C1-C4 alkylidene that N replaces；
Or R1R2N is together
R3, R4It is C1-C4 alkyl each independently, benzyl, wherein phenyl is unsubstituted or is replaced by C1-C4 alkyl；
R5It is H, C1-C4 alkyl；
M=2 or 3；
Method characteristic is, includes the following steps:
(1) structure formula (II) compound is dissolved in solvent, carries out chlorination reaction, obtains chloride (m shown in formula (III)
Or mixtures thereof 3) for 2 or hydrochloride；
(2) into the hydrochloride of or mixtures thereof chloride shown in formula (III) (m is 2 or 3), alcohol compound is added, stirs
It mixes heating and carries out alcoholysis reaction, generate the hydrochloride of structure formula (I) compound.
(3) by the hydrochloride of obtained structure formula (I) compound represented, neutralized, purification obtains structure formula (I) chemical combination
Object.
Wherein chlorination reagent used in the chlorination reaction of step (1) is chlorine, chlorosulfuric acid or phosphorus pentachloride, it is preferable to use sulfonyl
Chlorine, the solvent of reaction can be alkane, chloralkane, such as heptane, 1,2- dichloroethanes.
Wherein alcohol compound used in the alcoholysis reaction of step (2) is C1-C4Alcohol compound, such as methanol, second
Alcohol, isopropanol or butanol are, it is preferable to use methanol.
The hydrochloride for the structure formula (I) compound that above-mentioned reaction obtains, for example neutralizes through widely-known technique method, pure
Change obtains structure formula (I) pure compounds, and the methods of common extraction or recrystallization can be used in purifying.
The particular compound of Norleucyl base thiophenols shown in formula I includes (I -1)~(I -6):
Invention effect
New preparation process provided by the present invention, reaction condition is simple and easy, and raw materials used routine is easy to get, stable yield,
Suitable for industrial production.
Specific embodiment
The preparation of embodiment 1 2- methyl -2- (4- morpholinyl) -1- (4- mercaptophenyl) -1- acetone
(1) in 100ml there-necked flask, 2- methyl -2- (4- morpholinyl) -1- [4- (methylsulfany) phenyl] -1- acetone is added
11.2g and dichloroethanes 30g installs snorkel and device for absorbing tail gas additional；Stirring is cooled to 0 DEG C in after uniform solution, slowly logical
Enter chlorine reaction；Sampling in every 1 hour is primary, until 2- methyl -2- (4- morpholinyl) -1- [4- (methylsulfany) phenyl] -1- acetone
It disappears, analyzes and contain 2- methyl -2- (4- morpholinyl) -1- [4- (dichloromethyl sulfenyl) phenyl] -1- acetone and 2- in reaction solution
Methyl -2- (4- morpholinyl) -1- [4- (trichloromethyl sulfenyl) phenyl] -1- acetone stops reaction, with nitrogen stripping dechlorination, takes off
Except dichloroethanes, filtering obtains 2- methyl -2- (4- morpholinyl) -1- [4- (dichloromethyl sulfenyl) phenyl] -1- acetone and 2- first
The hydrochloride mixture of base -2- (4- morpholinyl) -1- [4- (trichloromethyl sulfenyl) phenyl] -1- acetone (is analyzed to identify through LC-MS
Structure, the ratio that HPLC analyzes them is 3:6) 12.2g；
(2) 2- methyl -2- (4- morpholinyl) -1- [4- (dichloromethyl sulfenyl) phenyl] -1- acetone and 2- methyl -2- are weighed
The hydrochloride mixture 11.0g of (4- morpholinyl) -1- [4- (trichloromethyl sulfenyl) phenyl] -1- acetone in 100ml there-necked flask,
Methanol 30g is added, stirred under nitrogen atmosphere heating flows back 6 hours.
(3) methanol and all low-boiling-point substances are distilled out, residue is added in 50ml dimethyl carbonate, and 30ml 10% is added
NaOH solution under nitrogen protection, stirs 15 minutes, stands liquid separation, separate water phase.Under nitrogen protection, with dilute hydrochloric acid by water phase pH
The extraction of 30ml dimethyl carbonate is added with being adjusted to 5-6 in value, and dimethyl carbonate is recovered under reduced pressure in dimethyl carbonate solution, remaining
Object 5.1g, faint yellow solid, 69.5-71.6 DEG C of fusing point, it is 2- methyl -2- (4- morpholinyl)-that nucleus magnetic hydrogen spectrum analysis, which is object,
1- (4- mercaptophenyl) -1- acetone.1H-NMR data (solvent C DCl3): δ 1.31ppm, s, 6H；δ2.56ppm,d,4H；δ
3.69ppm,d,4H；δ3.60ppm,s,1H；δ7.25ppm,d,2H；δ8.45ppm,d,2H.
The preparation of embodiment 2 2- methyl -2- (4- morpholinyl) -1- (4- mercaptophenyl) -1- acetone
(1) in 100ml there-necked flask, 2- methyl -2- (4- morpholinyl) -1- [4- (methylsulfany) phenyl] -1- acetone is added
14.0g and dichloroethanes 28g installs snorkel and device for absorbing tail gas additional；Stirring is cooled to 20 DEG C in after uniform solution, is added dropwise
Chlorosulfuric acid 20g；20-30 DEG C is reacted 4 hours, and reaction solution is cooled to -10 DEG C, there is solid precipitation, is filtered, is obtained 2- methyl -2- (4-
Morpholinyl) -1- [4- (dichloromethyl sulfenyl) phenyl] -1- acetone and 2- methyl -2- (4- morpholinyl) -1- [4- (trichloromethyl sulphur
Base) phenyl] -1- acetone hydrochloride mixture (ratio that HPLC analyzes them is 1:9) 16.5g.
(2) 2- methyl -2- (4- morpholinyl) -1- [4- (dichloromethyl sulfenyl) phenyl] -1- acetone and 2- methyl -2- are weighed
The hydrochloride mixture 16.0g of (4- morpholinyl) -1- [4- (trichloromethyl sulfenyl) phenyl] -1- acetone in 100ml there-necked flask,
Methanol 50g is added, stirred under nitrogen atmosphere heating flows back 6 hours.
(3) methanol and all low-boiling-point substances are distilled out, residue is added in 60ml dimethyl carbonate, and 50ml 10% is added
NaOH solution under nitrogen protection, stirs 15 minutes, stands liquid separation, separate water phase.Under nitrogen protection, with dilute hydrochloric acid by water phase pH
Value is adjusted to 5-6, and the extraction of 40ml dimethyl carbonate is added, and dimethyl carbonate, residue is recovered under reduced pressure in dimethyl carbonate solution
8.5g；Nucleus magnetic hydrogen spectrum analysis is object 2- methyl -2- (4- morpholinyl) -1- (4- mercaptophenyl) -1- acetone.
The preparation of embodiment 3 2- methyl -2- (1- piperidyl) -1- (4- mercaptophenyl) -1- acetone
(1) in 100ml there-necked flask, 2- methyl -2- (1- piperidyl) -1- [4- (methylsulfany) phenyl] -1- acetone is added
13.8g and dichloroethanes 25g installs snorkel and device for absorbing tail gas additional；Stirring is cooled to 20 DEG C in after uniform solution, is added dropwise
Chlorosulfuric acid 20g；20-30 DEG C is reacted 4 hours, and reaction solution is cooled to -10 DEG C, there is solid precipitation, is filtered, is obtained solid 16.2g,
HPLC analyzes 2- methyl -2- (4- morpholinyl) -1- [4- (dichloromethyl sulfenyl) phenyl] -1- acetone and 2- methyl -2- (4- morpholine
Base) -1- [4- (trichloromethyl sulfenyl) phenyl] -1- acetone hydrochloride mixture, their ratio is 1:9.
(2) 2- methyl -2- (1- piperidyl) -1- [4- (dichloromethyl sulfenyl) phenyl] -1- acetone and 2- methyl -2- are weighed
The hydrochloride mixture 15.0g of (1- piperidyl) -1- [4- (trichloromethyl sulfenyl) phenyl] -1- acetone in 100ml there-necked flask,
Methanol 50g is added, stirred under nitrogen atmosphere heating flows back 6 hours.
(3) methanol and all low-boiling-point substances are distilled out, residue is added in 60ml dimethyl carbonate, and 45g 10%NaOH is added
Solution under nitrogen protection, stirs 15 minutes, stands liquid separation, separate water phase.Under nitrogen protection, with dilute hydrochloric acid by aqueous pH values tune
To 5-6, and the extraction of 40ml dimethyl carbonate is added, dimethyl carbonate is mutually evaporated in vacuo, recycles dimethyl carbonate, it is remaining
Object is pale yellow viscous liquid, and quality 8g is analyzed to identify as 2- methyl -2- (1- piperidyl) -1- (4- mercaptophenyl) -1- third
Ketone.1H-NMR data (solvent C DCl3): δ 1.51ppm, m, 2H (CH2)；δ1.53ppm,m,4H(2CH2)；δ1.27ppm,s,6H
(2CH3)；δ2.48ppm,m,4H(2NCH2)；δ3.58ppm,s,1H(SH)；δ7.23/7.26ppm,d,2H(2ArH)；δ8.50/
8.53ppm,d,2H(2ArH)。
Claims (7)
1. the preparation method of compound Norleucyl base benzenethiol shown in a kind of formula (I), reaction equation:
Wherein
R1, R2It is C1-C4 alkyl each independently, or by R5O、R5R6The C1-C4 alkylidene that N replaces；
Or R1R2N is together
R3, R4It is C1-C4 alkyl each independently, benzyl, wherein phenyl is unsubstituted or is replaced by C1-C4 alkyl；
R5It is H, C1-C4 alkyl；
M=2 or 3；
Method characteristic is, includes the following steps:
(1) structure formula (II) compound is dissolved in solvent, carry out chlorination reaction, obtain chloride shown in formula (III) (m be 2 or
Or mixtures thereof 3) hydrochloride；
(2) into the hydrochloride of or mixtures thereof chloride shown in formula (III) (m is 2 or 3), alcohol compound is added, stirring adds
Heat carries out alcoholysis reaction, generates the hydrochloride of structure formula (I) compound；
(3) by the hydrochloride of obtained structure formula (I) compound represented, neutralized, purification obtains structure formula (I) compound.
2. preparation method according to claim 1, wherein chlorination reagent used in chlorination reaction is chlorine.
3. preparation method according to claim 1, wherein chlorination reagent used in chlorination reaction is chlorosulfuric acid.
4. preparation method according to claim 1, wherein chlorination reagent used in chlorination reaction is phosphorus pentachloride.
5. preparation method according to claim 1, wherein alcohol compound used in alcoholysis reaction is C1-C4Alcohols chemical combination
Object.
6. preparation method according to claim 1, wherein alcohol compound used in alcoholysis reaction is methanol.
7. preparation method according to claim 1, wherein formula (I) compound specific structure is formula (I -1)~(I -6):
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012007070A (en) * | 2010-06-24 | 2012-01-12 | Fujifilm Corp | Ink composition, ink set and image forming method |
| JP2012007071A (en) * | 2010-06-24 | 2012-01-12 | Fujifilm Corp | Ink composition, ink set and image forming method |
| CN102924352A (en) * | 2011-08-10 | 2013-02-13 | 北京英力科技发展有限公司 | Method for synthesizing 4-mercaptobenzoate |
| CN102958946A (en) * | 2011-07-29 | 2013-03-06 | 北京英力科技发展有限公司 | Mercapto-benzophenone compounds, compositions and preparation methods thereof |
-
2017
- 2017-07-31 CN CN201710637519.4A patent/CN109320476A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012007070A (en) * | 2010-06-24 | 2012-01-12 | Fujifilm Corp | Ink composition, ink set and image forming method |
| JP2012007071A (en) * | 2010-06-24 | 2012-01-12 | Fujifilm Corp | Ink composition, ink set and image forming method |
| CN102958946A (en) * | 2011-07-29 | 2013-03-06 | 北京英力科技发展有限公司 | Mercapto-benzophenone compounds, compositions and preparation methods thereof |
| CN102924352A (en) * | 2011-08-10 | 2013-02-13 | 北京英力科技发展有限公司 | Method for synthesizing 4-mercaptobenzoate |
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Application publication date: 20190212 |