CN107840831A - The synthetic method of quaternary ammonium salt 73 - Google Patents
The synthetic method of quaternary ammonium salt 73 Download PDFInfo
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- CN107840831A CN107840831A CN201710890607.5A CN201710890607A CN107840831A CN 107840831 A CN107840831 A CN 107840831A CN 201710890607 A CN201710890607 A CN 201710890607A CN 107840831 A CN107840831 A CN 107840831A
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- quaternary ammonium
- ammonium salt
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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Abstract
The present invention relates to the synthetic method of quaternary ammonium salt 73, comprise the following steps：(1) in alcohols solvent, the mercaptan of 4 methylthiazol 2 reacts with iodo normal heptane in the presence of base, obtain 2 heptan 4 methylthiazol of sulfenyl, the temperature of the reaction is 60 90 DEG C；(2) methylthiazol of sulfenyl in 2 heptan 4 is reacted under conditions of 110~140 DEG C with iodo normal heptane, cools down, obtain the iodo salt of 3 heptyl sulfenyl in 2 heptan, 4 methylthiazol 3；(3) in organic solvent, the iodo salt of 2 heptan of 3 heptyl, 4 methylthiazol of sulfenyl 3 the iodo salt back flow reaction of 4 dimethylthiazole 3, produces the quaternary ammonium salt 73 with 2 in the presence of organic base.The present invention synthetic method can be in high yield quaternary ammonium salt 73 is prepared, yield can reach more than 90%, and product purity reaches more than 99.9%, reach medicinal rank.
Description
Technical field
The present invention relates to technical field of organic synthesis, more particularly to a kind of synthetic method of quaternary ammonium salt -73.
Background technology
Thiazole quaternary ammonium salt has excellent antistatic, sterilization and antiseptic power, can be used as antistatic additive and softening agent etc.
It is widely used in weaving, recovers the oil, the field such as fiber, leather；Skin proud peaceful (quaternary ammonium salt -73) can be used for controlling for dark sore, whelk etc.
Treat, there is important application in cosmetic field, be widely used in shampoo as conditioner, bactericide, whitening agent etc., face is used
The personal-care supplies such as product, skin lotion field；The product, applied to pharmaceuticals industry, treats whelk acne as medical components
And dermatitis etc..
Up to this point, the synthesis case document report of double thiazole quaternary ammonium salt is seldom, and specific to Pi Aoning, China is specially
Sharp CN201410127645.1 discloses its synthetic method, and specific synthetic route is as follows：
The synthetic method is repeated in the present inventor, it is found that the yield of the 4th step is very low, and accessory substance is more in products therefrom,
Product purity is low.
The content of the invention
Based on this, the invention provides the novel synthesis of quaternary ammonium salt -73, this method can greatly improve quaternary ammonium salt -73
Synthesis yield and purity.
Concrete technical scheme is as follows：
A kind of synthetic method of quaternary ammonium salt -73, comprises the following steps：
(1) in alcohols solvent, 4- methylthiazol -2- mercaptan reacts with iodo normal heptane in the presence of base, obtains 2- heptan
Sulfenyl -4- methylthiazols, the temperature of the reaction is 60-90 DEG C；
(2) sulfenyl -4- methylthiazols in 2- heptan are reacted under conditions of 110~140 DEG C with iodo normal heptane, it is cold
But, 3- heptyl -2- sulfenyl in heptan -4- methylthiazol -3- iodo salt is obtained；
(3) in organic solvent, 3- heptyl -2- sulfenyls in heptan -4- methylthiazol -3- iodos salt the depositing in organic base
In lower and 2,4- dimethylthiazole -3- iodo salt back flow reactions, the quaternary ammonium salt -73 is produced；
Reaction scheme is as follows：
In wherein some embodiments, step (1) described alcohols solvent is methanol and/or ethanol.
In wherein some embodiments, step (1) includes：Added in reaction vessel the 4- methylthiazols -2- mercaptan,
The iodo normal heptane, the alkali and the alcohols solvent, are heated to flowing back, and it is small to react 1.5-2.5 at a reflux temperature
When, produce sulfenyl -4- in the 2- heptan methylthiazols.
In wherein some embodiments, step (1) described alkali is selected from NaOH, KOH, caustic alcohol, potassium tert-butoxide, 1,8- phenodiazines
At least one of the miscellaneous carbon -7- alkene of two ring 11, DIPEA and triethylamine.
In wherein some embodiments, step (1) described alkali is selected from NaOH or triethylamine.
In wherein some embodiments, mole of step (1) 4- methylthiazols -2- mercaptan and the iodo normal heptane
Than for 1：1~2.
In wherein some embodiments, the mol ratio of step (1) 4- methylthiazols -2- mercaptan and the alkali is 1:1
~2.
In wherein some embodiments, step (1) also includes：After reaction terminates, reaction mixture is evaporated under reduced pressure,
120~140 DEG C of cut is collected, produces sulfenyl -4- in the 2- heptan methylthiazols.
In wherein some embodiments, the reaction temperature in step (2) is 115~125 DEG C.
In wherein some embodiments, the reaction time in step (2) is 8~36h.
In wherein some embodiments, the reaction time in step (2) is 10~14h.
In wherein some embodiments, step (2) sulfenyl in the 2- heptan -4- methylthiazols rub with the iodo normal heptane
You are than being 1：1~5.
In wherein some embodiments, step (2) sulfenyl in the 2- heptan -4- methylthiazols rub with the iodo normal heptane
You are than being 1：2.5~3.5.
In wherein some embodiments, step (3) sulfenyl in the 3- heptyl -2- heptan -4- methylthiazols -3- iodos salt with
The mol ratio of 2, the 4- dimethylthiazoles -3- iodo salt is 1：1~1.2.
In wherein some embodiments, step (3) sulfenyl in the 3- heptyl -2- heptan -4- methylthiazols -3- iodos salt with
The mol ratio of 2, the 4- dimethylthiazoles -3- iodo salt is 1：1~1.05.
In wherein some embodiments, the time of the back flow reaction described in step (3) is 8~24h.
In wherein some embodiments, the time of the back flow reaction described in step (2) is 10~14h.
In wherein some embodiments, the organic solvent described in step (3) is ethanol.
In wherein some embodiments, the organic base described in step (3) is DIPEA
The quaternary ammonium salt -73 of the present invention has advantages below and beneficial effect：
The present inventor is found surprisingly that in long-term experimentation, by controlling reaction condition, 4- methyl thiazoliums
Azoles -2- mercaptan and iodo normal heptane react, can selectivity substitution reaction occurs on sulphur atom, so as to obtain newization
Compound 2- sulfenyl in heptan -4- methylthiazols.And it is found surprisingly that, can be with as reaction raw materials using 2- sulfenyl in the heptan -4- methylthiazols
In high yield quaternary ammonium salt -73 are prepared, yield can reach more than 90%, and product purity reaches more than 99.9%, reach
Medicinal rank.The synthetic method of the quaternary ammonium salt -73 of the present invention is very simple, and high income, and the reaction time is short, combined coefficient
Height, be advantageous to the large-scale production of quaternary ammonium salt -73.
Brief description of the drawings
Fig. 1 is 2- sulfenyl in heptan -4- methylthiazols13C spectrograms；
Fig. 2 is the HMBC spectrograms of 2- sulfenyl in heptan -4- methylthiazols；
Fig. 3 is 2- sulfenyl in heptan -4- methylthiazols1H spectrograms；
Fig. 4 is 2,4- dimethylthiazole -3- iodo salt1H spectrograms；
Fig. 5 is the MS spectrograms of 2,4- dimethylthiazole -3- iodo salt；
Fig. 6 is quaternary ammonium salt -731H spectrograms；
Fig. 7 is the MS spectrograms of quaternary ammonium salt -73.
Embodiment
The synthetic method of the quaternary ammonium salt -73 of the present invention is further described in detail below in conjunction with specific embodiment.
The synthesis of 2- sulfenyl in the heptan -4- methylthiazols of embodiment 1
In 250ml there-necked flasks add 2- sulfydryl -4- methylthiazols (5.0g, 38.1mmol), iodo normal heptane (12.9g,
57.16mmol), sodium hydroxide (1.52g, 38.1mmol), ethanol 60ml, are heated to flow back, and react 2h, and point plate to raw material point disappears
Lose, be evaporated under reduced pressure, collect 120~140 DEG C of cut, obtain yellow liquid 7.1g, yield 80.3%.Structural identification spectrogram is as schemed
Shown in 1- Fig. 3.
By the sodium hydroxide in embodiment 1 replace with other alkali (KOH, caustic alcohol, potassium tert-butoxide, DBU, DIPEA or
TEA), 2- sulfenyl in heptan -4- methylthiazols can smoothly be prepared, yield is between 50-80%.
The synthesis of 2- sulfenyl in the heptan -4- methylthiazols of embodiment 2
In 250ml there-necked flasks add 2- sulfydryl -4- methylthiazols (5.0g, 38.1mmol), iodo normal heptane (8.6g,
38.1mmol), triethylamine (3.86g, 38.1mmol), methanol 60ml, are heated to flow back, and react 2h, and point plate to raw material point disappears,
It is evaporated under reduced pressure, collects 120~140 DEG C of cut, obtain yellow liquid 7.0g, yield 80.0%.
The synthesis of the quaternary ammonium salt -73 of embodiment 3
Step 1) 2, the synthesis of 4- dimethylthiazole -3- iodos salt (intermediate 1)
In 100ml there-necked flasks add 2.4- dimethylthiazoles (5.0g, 44.18mmol), iodo normal heptane (30.0g,
132.54mmol), 120 DEG C are heated to, reacts 12h, is cooled down, filtering, ethyl acetate washing filter cake, obtains white solid 11.9g,
Yield 79.4%.Structural identification spectrogram is as shown in fig. 4-5.
The synthesis of step 2) 3- heptyl -2- sulfenyl in heptan -4- methylthiazol -3- iodos salt (intermediate 2)
In 250ml there-necked flasks add embodiment 1 synthesize 2- sulfenyl in heptan -4- methylthiazols (12.78g, 55.7mmol),
Iodo normal heptane (37.79g, 167.1mmol) is heated to 120 DEG C, reacts 12h, obtains brown oil, do not process and be directly used in
React in next step.
The synthesis of step 3) quaternary ammonium salt -73
Added in the brown oil obtained to step 2) 2,4- dimethylthiazole -3- iodos salt (18.9g,
55.7mmol), ethanol 100ml, DIPEA 100ml, reaction 12h is stirred at reflux, point plate to raw material point disappears, and stops stirring, quiet
Put and be cooled to room temperature, separate out solid, filter and washed with ethanol, obtain yellow solid 27.3g, yield 91.0%, HPLC purity
99.9%.Structural identification spectrogram is as Figure 6-Figure 7.
The synthesis of 2- sulfenyl in the heptan -4- methylthiazols of comparative example 1
In 250ml there-necked flasks add 2- sulfydryl -4- methylthiazols (5.0g, 38.1mmol), iodo normal heptane (12.9g,
57.16mmol), sodium hydroxide (1.52g, 38.1mmol), ethyl acetate 60ml, are heated to flow back, and react 2h, are evaporated under reduced pressure,
120~140 DEG C of cut is collected, obtains yellow liquid 4.36g, yield 50%.
The synthesis of the quaternary ammonium salt -73 of comparative example 2
Synthetic route is as follows：
Step 1) 2, the synthesis of 4- dimethylthiazole -3- iodo salt
In 100ml there-necked flasks add 2.4- dimethylthiazoles (5.0g, 44.18mmol), iodo normal heptane (30.0g,
132.54mmol), 120 DEG C are heated to, reacts 12h, is cooled down, filtering, ethyl acetate washing filter cake, obtains white solid 11.9g,
Yield 79.4%.
The synthesis of step 2) 3- heptyl -4- dimethylthiazoles -2 (3H)-thio ketone
2- sulfydryl 4- methylthiazols (5.0g, 38.1mmol) are added in 250ml there-necked flask, add 60ml methanol,
Stir, iodo normal heptane (12.9g, 57.16mmol) is then added dropwise, plate is put after 20h is stirred at room temperature；After raw material point disappears,
Natrium carbonicum calcinatum (2.0g) is added, distilled water 190ml, regulation reaction solution pH is alkalescent；With ethanol extraction until aqueous phase is nothing
Color, aqueous phase point plate is without product；With anhydrous sodium sulfate drying and organic phase is evaporated under reduced pressure, steams ethanol, obtains brown oil 7.0g,
Yield 79.9%.
The synthesis of step 3) 3- heptyl -2- sulfenyl in heptan -4- methylthiazol -3- iodo salt
3- heptyl -4- methylthiazol -2 (the 3H)-thio ketone that synthesizes is added in step 2 in 250ml there-necked flasks
(12.78g, 55.7mmol), iodo normal heptane (37.79g, 167.1mmol), under nitrogen protection, 140 DEG C of stirring reaction 16h, obtain
Brown oil, do not process to be directly used in and react in next step.
The synthesis of step 4) quaternary ammonium salt -73
Added in the brown oil obtained to step 3) 2,4- dimethylthiazole -3- iodos salt (18.9g,
55.7mmol), ethanol 100ml, DIPEA 100ml, 90 DEG C of reaction 12h, point plate to raw material point disappear, stop stirring, stand cold
But to room temperature, solid is separated out, filters and is washed with ethanol, obtain yellow solid 23.7g, yield 79.6%, HPLC purity
91.8%, purity is relatively low, and gained solid is washed with ethanol again, obtains yellow solid 10.8g, yield 36.0%, HPLC is pure
Degree 97.1%.
Each technical characteristic of embodiment described above can be combined arbitrarily, to make description succinct, not to above-mentioned reality
Apply all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, the scope that this specification is recorded all is considered to be.
Embodiment described above only expresses the several embodiments of the present invention, and its description is more specific and detailed, but simultaneously
Can not therefore it be construed as limiting the scope of the patent.It should be pointed out that come for one of ordinary skill in the art
Say, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the protection of the present invention
Scope.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (10)
1. a kind of synthetic method of quaternary ammonium salt -73, it is characterised in that comprise the following steps：
(1) in alcohols solvent, 4- methylthiazol -2- mercaptan in the presence of base with iodo normal heptane react, obtain 2- sulfenyls in heptan -
4- methylthiazols, the temperature of the reaction is 60-90 DEG C；
(2) sulfenyl -4- methylthiazols in 2- heptan are reacted under conditions of 110~140 DEG C with iodo normal heptane, cools down, obtain
3- heptyl -2- sulfenyl in heptan -4- methylthiazol -3- iodo salt；
(3) in organic solvent, 3- heptyl -2- sulfenyls in the heptan -4- methylthiazol -3- iodo salt is in the presence of organic base
With 2,4- dimethylthiazole -3- iodo salt back flow reactions, the quaternary ammonium salt -73 is produced；
Reaction scheme is as follows：
2. the synthetic method of quaternary ammonium salt -73 according to claim 1, it is characterised in that step (1) described alcohols solvent is
Methanol and/or ethanol.
3. the synthetic method of quaternary ammonium salt -73 according to claim 2, it is characterised in that step (1) includes：Hold in reaction
4- methylthiazols -2- the mercaptan, the iodo normal heptane, the alkali and the alcohols solvent are added in device, is heated to back
Stream, and 1.5-2.5 hours are reacted at a reflux temperature, produce sulfenyl -4- in the 2- heptan methylthiazols.
4. the synthetic method of the quaternary ammonium salt -73 according to claim any one of 1-3, it is characterised in that step (1) described alkali
Selected from NaOH, KOH, caustic alcohol, potassium tert-butoxide, the carbon -7- alkene of 1,8- diazabicylos 11, DIPEA and three second
At least one of amine.
5. the synthetic method of the quaternary ammonium salt -73 according to claim any one of 1-3, it is characterised in that step (1) described 4-
The mol ratio of methylthiazol -2- mercaptan and the iodo normal heptane is 1：1~2；And/or step (1) the 4- methylthiazols-
The mol ratio of 2- mercaptan and the alkali is 1:1~2.
6. the synthetic method of the quaternary ammonium salt -73 according to claim any one of 1-3, it is characterised in that step (1) is also wrapped
Include：After reaction terminates, reaction mixture is evaporated under reduced pressure, collects 120~140 DEG C of cut, produce the sulfenyl in 2- heptan-
4- methylthiazols.
7. the synthetic method of the quaternary ammonium salt -73 according to claim any one of 1-3, it is characterised in that anti-in step (2)
It is 115~125 DEG C to answer temperature；And/or the reaction time in step (2) is 8~36h.
8. the synthetic method of the quaternary ammonium salt -73 according to claim any one of 1-3, it is characterised in that step (2) described 2-
Heptan sulfenyl -4- methylthiazols and the mol ratio of the iodo normal heptane be 1：1~5；And/or step (3) 3- heptyl -2-
Heptan sulfenyl -4- methylthiazols -3- iodos salt and the mol ratio of 2, the 4- dimethylthiazoles -3- iodo salt be 1：1~
1.2。
9. the synthetic method of the quaternary ammonium salt -73 according to claim any one of 1-3, it is characterised in that described in step (3)
Time of back flow reaction be 8~24h.
10. the synthetic method of the quaternary ammonium salt -73 according to claim any one of 1-3, it is characterised in that institute in step (3)
The organic solvent stated is ethanol；And/or the organic base described in step (3) is DIPEA.
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| CN110305074A (en) * | 2019-04-02 | 2019-10-08 | 上海克琴科技有限公司 | A kind of green synthesis method of quaternary ammonium salt -73 |
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| CN110305074A (en) * | 2019-04-02 | 2019-10-08 | 上海克琴科技有限公司 | A kind of green synthesis method of quaternary ammonium salt -73 |
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Application publication date: 20180327 |