CN1323791A - Prepn. of N-butyl benzoyl-2-sulfonyl inner imine - Google Patents
Prepn. of N-butyl benzoyl-2-sulfonyl inner imine Download PDFInfo
- Publication number
- CN1323791A CN1323791A CN 01115315 CN01115315A CN1323791A CN 1323791 A CN1323791 A CN 1323791A CN 01115315 CN01115315 CN 01115315 CN 01115315 A CN01115315 A CN 01115315A CN 1323791 A CN1323791 A CN 1323791A
- Authority
- CN
- China
- Prior art keywords
- sulfonyl
- imine
- butylbenzene formyl
- crystal water
- reaction
- 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
- 150000002466 imines Chemical class 0.000 title claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 5
- 150000001350 alkyl halides Chemical class 0.000 claims abstract 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims abstract 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 239000013078 crystal Substances 0.000 claims description 6
- 230000002152 alkylating effect Effects 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical group [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 4
- -1 polyoxyethylene Polymers 0.000 claims description 4
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical group [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 3
- LQOBMKYCRQDMTN-UHFFFAOYSA-N 3-(2-ethylphenyl)pentan-3-amine;hydrochloride Chemical compound Cl.CCC1=CC=CC=C1C(N)(CC)CC LQOBMKYCRQDMTN-UHFFFAOYSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims 1
- 125000002091 cationic group Chemical group 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000008595 infiltration Effects 0.000 claims 1
- 238000001764 infiltration Methods 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims 1
- 239000002994 raw material Substances 0.000 claims 1
- 239000011347 resin Substances 0.000 claims 1
- 229920005989 resin Polymers 0.000 claims 1
- 229940081974 saccharin Drugs 0.000 claims 1
- 235000019204 saccharin Nutrition 0.000 claims 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 abstract 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 229940085605 saccharin sodium Drugs 0.000 description 5
- 229940093265 berberine Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000031709 bromination Effects 0.000 description 3
- 238000005893 bromination reaction Methods 0.000 description 3
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 3
- 238000010298 pulverizing process Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- OCKPCBLVNKHBMX-UHFFFAOYSA-N butylbenzene Chemical compound CCCCC1=CC=CC=C1 OCKPCBLVNKHBMX-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 235000014347 soups Nutrition 0.000 description 2
- 238000010025 steaming Methods 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- 241001615463 Trichogenes Species 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 description 1
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000035617 depilation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003746 feather Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention discloses method of preparing N-orthobutyl benzoyl-2-sulfonylendo imine, it includes that under the existance of phase transfer catalyst and in the phydrocarbon solvent, to proceed reaction between benzosulfimide and alkyl halide.
Description
The present invention relates to the method for a kind of synthetic N-n-butylbenzene formyl-2-sulfonyl inner imine, utilize phase-transfer catalyst exactly in the solid-liquid two-phase, with the saccharin sodium one-step synthesis N-n-butylbenzene formyl-2-sulfonyl inner imine that contains crystal water.N-n-butylbenzene formyl-2-sulfonyl inner imine is for having following structural
A kind of white crystal.
The existing technology of preparation N-n-butylbenzene formyl-2-sulfonyl inner imine is the alkylating reagent saccharin sodium reaction good with pulverizing drying treatment in advance, manys pulverizing and dry two procedures than the present invention, and is time-consuming also uneconomical.
At the shortcoming of prior art, the present invention proposes improving one's methods of a kind of N-of production n-butylbenzene formyl-2-sulfonyl inner imine.According to the present invention, this compound is that directly usefulness contains the saccharin sodium and the alkylating reagent reaction of crystal water and makes.
The used phase-transfer catalyst of the present invention is Tetrabutyl amonium bromide, triethyl benzyl ammonia chloride, cetyl trimethylammonium bromide, polyoxyethylene glycol, Zeo-karb etc., preferably Tetrabutyl amonium bromide.Catalyst levels is 2%～7% mole, is preferably 5% mole.
The used alkylating reagent of the present invention is a bromination of n-butane, and the mol ratio of this alkylating reagent and saccharin sodium is 0.7～1.4, preferred ratio 1.1.
The reaction required time of the present invention time more required than prior art is wanted much shorter, has simplified the purifying formality, makes operation more simple and easy to do.
The productive rate of N-n-butylbenzene formyl of the present invention-2-sulfonyl inner imine is up to more than 95%.And prior art will be 86.2% (Zhong Qi with the prior productive rate of pulverizing the good saccharin sodium of drying, chemical reagent 198810 (1) 47～48) and 90% (Celso F.Perez, Organic Prepartions and Procedures INT16 (1) 37～41,1984).
Reaction process of the present invention does not need other monitoring, and for example whether the thin-layer chromatography monitoring reaction carries out fully.The present invention then determines reaction process according to aquifer yield in reaction process.Save the operation of other detection.
Another advantage of the present invention is the reaction yield height, and generally between 96%～98%, product purity is also high for productive rate, 98%～99%, and mp39～41 ℃.
Be reflected in the four-hole bottle and carry out, this four-hole bottle is equipped with agitator, thermometer, water trap and reflux cooler.
Embodiment one:
In being housed, 1000 milliliters of four-hole bottles of agitator, thermometer, water trap and reflux cooler add o-benzoic sulfimide sodium salt (C
7H
4O
3NSNa2H
2O) 121 grams (0.5mol), 350 milliliters of toluene, reflux, after minute water outlet is near 18 milliliters, stop heating, after reacting liquid temperature drops to below 80 ℃, add Tetrabutyl amonium bromide (TBAB) 8 grams respectively, 54 milliliters of bromination of n-butane, heating reflux reaction 12 hours stops heating, after reaction mixture drops to below 85 ℃, add 100 milliliters in water, stirred standing demix, branch vibration layer 30 minutes.Behind the oil reservoir pressure reducing and steaming toluene, 134～136 ℃/23-30Pa cut is collected in rectification under vacuum, product 117 grams, mp40～41 ℃, productive rate 97.4%.
Embodiment two:
In 1000 milliliters of four-hole bottles of agitator, water trap, thermometer and reflux cooler are housed, add o-benzoyl sulfonyl inner imine sodium salt (C
7H
4O
3NSNa2H
aO) 242 grams, 650 milliliters of toluene.Reflux three hours, tell 35 ml waters after, stop heating, reacting liquid temperature drops to below 80 ℃ the back and adds cetyl trimethylammonium bromide (HTMAB) 18 grams, 110 milliliters of bromination of n-butane.Reflux 12 hours, stop the heating, cool to below 85 ℃ after, add 200 milliliters in water, stir after 30 minutes, standing demix discards water layer, oil reservoir pressure reducing and steaming toluene, rectification under vacuum, 134～136 ℃/25～30Pa of collection slips and divides, and gets product 227.1 grams, productive rate 95%.mp40℃～41℃。
Embodiment three:
Measure the short effect of oozing of N-n-butylbenzene formyl-2-sulfonyl inner imine.
With φ=75% ethanol preparation 1.67GBqL
-1 3The contrast liquid of H-Berberine is got 1.92mL
3H-Berberine contrast liquid adds the azone soup that 80 μ L azones are mixed with φ=4%, uses the N-n-butylbenzene formyl-2-sulfonyl inner imine soup that contains φ=4% with the quadrat method preparation.Get 10 of mouse, losing hair or feathers with trichogen in the back, exposes skin, gets the back that 1.5cm * 1.5cm gauze is layered on the depilation mouse open and flatly, gets
3H-Berberine contrast liquid 100 μ L evenly coat on the gauze, use immobilization with adhesive tape then, get blood 20 μ L respectively at 0.5,1,2,4,6,12,24 hour from mouse socket of the eye vein and place small test tube, add formic acid, H
2O
2Each 100uL is at 60 ℃ of digestion 30min.Get Digestive system 100uL and add and to have surveyed background and be added with in the scintillation vial of 7mL scintillation solution, place liquid to dodge spectrometer and measure, measure 10min, with F
TSIECarrying out DPM for the quench correction factor restores.With with quadrat method replication φ=4% azone and φ=4%N-n-butylbenzene formyl-2-sulfonyl inner imine sample sets, its result such as table 1.
Table 1N-n-butylbenzene formyl-2-sulfonyl inner imine and the short effect of oozing of azone.
| Sample | Contrast | Azone | N-n-butylbenzene formyl-2-sulfonyl inner imine |
| S/GBq·L -1h -1 | ?9.168 | ??35.388 | ???????????106.016 |
| ???S/S Contrast | ?1.00 | ??3.86 | ???????????11.56 |
| ???S/S Azone | ?- | ??1.00 | ???????????2.99 |
Azone can improve 3.86 times of the bioavailabilities of the Berberine of transdermal administration as shown in Table 1, and N-n-butylbenzene formyl-2-sulfonyl inner imine can improve 11.56 times.This shows that N-n-butylbenzene formyl-2-sulfonyl inner imine has the stronger short effect of oozing than azone, and it is short, and to ooze effect be 2.99 times of azone.
Claims (9)
1, a kind of method for preparing N-n-butylbenzene formyl 2-sulfonyl inner imine, it has comprised under the situation of phase-transfer catalyst existence, the saccharin and the haloalkane that contain crystal water is reacted.
2, the method for claim 1, wherein said varsol is cyclohexane, normal hexane, benzene, toluene, sherwood oil.
3, the method for claim 1, wherein said phase-transfer catalyst is a Tetrabutyl amonium bromide, triethyl benzyl ammonia chloride, polyoxyethylene glycol, cetyl trimethylammonium bromide or cationic exchange resin.
4, the method for claim 1, wherein said reaction are to carry out 55 ℃～140 ℃ temperature range.
5, the method for claim 1 is comprising the step of removing moisture and crystal water in the raw material in reaction process.
6, method as claimed in claim 5, wherein moisture and crystal water are removed by water trap.
7, the method for claim 1, wherein catalyst levels is 2%～7% mole.
8, the mol ratio of imines is 0.7～1.4 in the method for claim 1, alkylating reagent and adjacent sulfonyl-benzoyl.
9, by the N-n-butylbenzene formyl 2-sulfonyl inner imine of the method for claim 1-8 preparation as the transdermal infiltration accelerating agent.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01115315 CN1323791A (en) | 2001-04-19 | 2001-04-19 | Prepn. of N-butyl benzoyl-2-sulfonyl inner imine |
| AU2002308926A AU2002308926A1 (en) | 2001-04-19 | 2002-04-17 | The method of preparing of n-n-alkyl benzoyl-2-sulfonylendoimine |
| PCT/CN2002/000265 WO2003074503A1 (en) | 2001-04-19 | 2002-04-17 | The method of preparing of n-n-alkyl benzoyl-2-sulfonylendoimine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01115315 CN1323791A (en) | 2001-04-19 | 2001-04-19 | Prepn. of N-butyl benzoyl-2-sulfonyl inner imine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1323791A true CN1323791A (en) | 2001-11-28 |
Family
ID=4661881
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 01115315 Pending CN1323791A (en) | 2001-04-19 | 2001-04-19 | Prepn. of N-butyl benzoyl-2-sulfonyl inner imine |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN1323791A (en) |
| AU (1) | AU2002308926A1 (en) |
| WO (1) | WO2003074503A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945349A (en) * | 2015-07-16 | 2015-09-30 | 河南省化工研究所有限责任公司 | Method for preparing 1,2-benzisothiazole-3 (2H) ketone-2-butyl-1,1-dioxide |
| CN114453027A (en) * | 2021-12-17 | 2022-05-10 | 苏州大学 | A kind of catalyst composition, its application and the synthetic method of bixazone |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5618970A (en) * | 1979-07-25 | 1981-02-23 | Mitsui Toatsu Chem Inc | Preparation of alpha-halogeno-beta-benzosulfimido- propionitrile |
| JPS5618971A (en) * | 1979-07-26 | 1981-02-23 | Mitsui Toatsu Chem Inc | Alpha-halogeno-beta-benzosulfimidopropionitrile and its preparation |
| US5512589A (en) * | 1990-11-01 | 1996-04-30 | Sterling Winthrop Inc. | 2-saccharinylmethyl aryl carboxylates useful as proteolytic enzyme inhibitors and compositions and method of use thereof |
| CN1139402C (en) * | 2000-09-05 | 2004-02-25 | 北京科莱斯特医药技术研究所 | Usage of benzoisothiazole ketone compound being used as percutaneous medicine-feeding osmotic promoting agent and preparation process thereof |
-
2001
- 2001-04-19 CN CN 01115315 patent/CN1323791A/en active Pending
-
2002
- 2002-04-17 WO PCT/CN2002/000265 patent/WO2003074503A1/en not_active Ceased
- 2002-04-17 AU AU2002308926A patent/AU2002308926A1/en not_active Abandoned
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945349A (en) * | 2015-07-16 | 2015-09-30 | 河南省化工研究所有限责任公司 | Method for preparing 1,2-benzisothiazole-3 (2H) ketone-2-butyl-1,1-dioxide |
| CN114453027A (en) * | 2021-12-17 | 2022-05-10 | 苏州大学 | A kind of catalyst composition, its application and the synthetic method of bixazone |
| CN114453027B (en) * | 2021-12-17 | 2023-12-15 | 苏州大学 | A kind of catalyst composition, its application and the synthesis method of bistrifen |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002308926A1 (en) | 2003-09-16 |
| WO2003074503A1 (en) | 2003-09-12 |
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |