CN108863980A - A method of synthesis 1- (5- benzothiazolyl) ethyl ketone - Google Patents
A method of synthesis 1- (5- benzothiazolyl) ethyl ketone Download PDFInfo
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Abstract
The invention discloses a kind of new methods of 1- (5- benzothiazolyl) ethyl ketone, using parachloroacetophenone, the concentrated sulfuric acid, concentrated nitric acid, nine water vulcanized sodium, zinc powder and formic acid as raw material, compared with the synthesis that 1- (5- benzothiazolyl) ethyl ketone may be implemented under temperate condition.The low raw-material cost that the present invention uses, economic benefit are higher；Reaction condition is milder, and reaction speed is very fast, and conversion ratio is higher；Safety and environmental protection, it is easy to operate, it is more advantageous to its application in organic intermediate synthesis.
Description
(1) technical field
Present invention relates particularly to a kind of methods of 1- (5- benzothiazolyl) ethyl ketone.
(2) background technique
1- (5- benzothiazolyl) ethyl ketone is a kind of important medicine intermediate and pesticide intermediate in organic synthesis,
It can be used as photographic material and rubber accelerator.So develop novel 1- (5- benzothiazolyl) ethyl ketone synthetic method no matter
It is all to be of great significance for scientific research or actual production.But up to the present, about the synthesis of such compound
Method report is very few.The pertinent literature for announcing out only has two, one is with bromo benzothiazole and tributyl (1- second
Ethoxy ethylene) tin progress electrophilic substitution reaction (Preparation of substituted heteroaryl piperazines
and piperidines as glycosidase inhibitors； Quattropani,Anna；Kulkarni,Santosh
S.；Giri,Awadut Gajendra；Mar 3, 2016；WO 2016030443A1)；The second is with 4,5 dibromo methylthiazols
(Generation and Diels-Alder trapping of 4,5-bis is reacted with butenone
(bromomethylene) -4,5-dihydrothiazole；Jouve,Karine；Pautet,Felix；Domard,
Monique； Fillion,Houda；European Journal of Organic Chemistry, Pages 2047-2050；
1998).Both methods raw material is not easy to obtain, and economic cost is high, and reaction yield is lower, thus greatly limit this two
The large-scale application of kind method.
(3) summary of the invention
The object of the present invention is to provide a kind of new method of 1- (5- benzothiazolyl) ethyl ketone, with parachloroacetophenone,
The concentrated sulfuric acid, concentrated nitric acid, nine water vulcanized sodium, zinc powder and formic acid are raw material, compared with 1- (5- benzo thiophene may be implemented under temperate condition
Oxazolyl) ethyl ketone synthesis.
In order to achieve the above objectives, the technical solution adopted by the present invention is as follows：
1- (5- benzothiazolyl) ethyl ketone synthetic method shown in a kind of formula IV, it is characterised in that：The synthetic method
Specifically prepared in accordance with the following steps：
(1) by parachloroacetophenone shown in Formulas I under -20 DEG C~5 DEG C (preferably 0 DEG C), being dissolved in mass fraction is 98%
Concentrated sulfuric acid solvent in, the concentrated sulfuric acid solution of parachloroacetophenone is obtained, then to the concentrated sulfuric acid solution of the parachloroacetophenone
Middle addition nitration mixture is reacted at -20 DEG C~10 DEG C (preferably 0 DEG C), is tracked and is reacted by TLC, is obtained after fully reacting anti-
Liquid A is answered, it is post-treated to obtain 3- nitro -4- chloro-acetophenone shown in formula II；The additional amount of the concentrated sulfuric acid is with pair
The mass ratio of chloro-acetophenone is 1-5ml/g；The nitration mixture is that volume ratio is 1：1~3 (preferably 1：1.5) mass fraction
The mixed liquor for the concentrated sulfuric acid that concentrated nitric acid and mass fraction for 65%~68% are 98%；To chlorobenzene second shown in the Formulas I
Feed intake the ratio between the amount of substance of concentrated nitric acid in ketone and the nitration mixture is 1:1~2 (preferably 1:1.5)；
(2) 3- nitro -4- chloro-acetophenone shown in formula II obtained by step (1) is dissolved in organic solvent, nine water is added
Vulcanized sodium, at room temperature fully reacting obtain reaction solution B, post-treated to obtain 3- nitro -4- sulfydryl benzene second shown in formula III
Ketone；The additional amount of 3- nitro -4- chloro-acetophenone and the ratio between the amount of the nine aqueous sodium persulfate substances shown in the formula II be
1:0.8~2 (preferably 1:1.2)；
(3) 3- nitro -4- sulfydryl acetophenone shown in formula III obtained by step (2) is dissolved in formic acid, adds Zn
Powder is heated to 50~110 DEG C of (preferably 75 DEG C) fully reactings, obtains reaction liquid C, post-treated to obtain 1- shown in formula IV
(5- benzothiazolyl) ethyl ketone；The ratio between 3- nitro -4- sulfydryl acetophenone and the amount of substance of Zn powder shown in the formula III are
1:2~1:5 (preferably 1:3.5)；
Further, in step (1), preferred reaction time 0.5-2h.
Further, in step (1), the post-processing approach of the reaction solution A is：After reaction, reaction solution A is poured into
It in a large amount of ice water, is filtered under diminished pressure, collects filter cake and is recrystallized again after white solid is precipitated, is filtered under diminished pressure after cooling
To white crystal, with being drained after ice ethanol washing to get 3- nitro -4- chloro-acetophenone shown in the formula II.
Further, in step (2), preferred reaction time 1-6h.
Further, in step (2), the organic solvent is n,N-Dimethylformamide or dimethyl sulfoxide.
Further, in step (2), the additional amount of the organic solvent is with 3- nitro -4- chloro-acetophenone shown in formula II
The amount of substance is calculated as 0.5~2ml/mmol.
Further, in step (2), the post-processing approach of the reaction solution B is：After reaction, reaction solution B is fallen
Enter in a large amount of water, the PH to acid (preferably PH=4) of filtrate is adjusted after filtering, yellow solid is precipitated, is received after being filtered, washed
Collection filter cake is drained to get crude product, then carries out column chromatography for separation again to the crude product, is 6/1- with volume ratio
20/1 petrol ether/ethyl acetate mixed liquor is eluant, eluent, collects the eluent containing target compound, and drying after solvent is evaporated off,
Up to 3- nitro -4- sulfydryl acetophenone shown in the formula III.
Further, in step (3), preferred reaction time 1-5h.
Further, in step (3), the additional amount of the formic acid is with 3- nitro -4- sulfydryl benzene second shown in the formula III
The amount of the substance of ketone is calculated as 1~3ml/mmol.
Further, in step (3), the post-processing approach of the reaction liquid C is：After reaction, first by reaction liquid C mistake
Filter, then filtrate is rotated to one third, it is subsequently poured into the aqueous solution of sodium carbonate, is extracted with ethyl acetate after being sufficiently stirred,
It is washed with water after ethyl acetate layer is collected 3 times, then washed once with saturated salt solution, collect mistake after ethyl acetate layer drying
It filters, be spin-dried for carrying out column chromatography for separation again up to crude product to gained crude product, being petroleum ether/second of 6/1-20/1 with volume ratio
Acetoacetic ester mixed liquor is eluant, eluent, collects the eluent containing target compound, is dried after solvent is evaporated off to get 1- shown in formula IV
(5- benzothiazolyl) ethyl ketone.
Compared with prior art, the beneficial effects of the invention are as follows：
(1) low raw-material cost, economic benefit are higher；
(2) compared with prior art, reaction condition is milder, and reaction speed is very fast, and conversion ratio is higher；
(3) safety and environmental protection, it is easy to operate, it is more advantageous to its application in organic intermediate synthesis.
(4) specific embodiment
The present invention is described in further detail combined with specific embodiments below, but protection scope of the present invention and not only
It is limited to this.
Embodiment 1
(1) concentrated nitric acid that 4ml mass fraction is 65%~68% and the concentrated sulfuric acid that 6ml mass fraction is 98% are taken, it will be dense
Nitric acid dropping is prepared into nitration mixture into the concentrated sulfuric acid.6.2g (40mmol) parachloroacetophenone and the 10ml concentrated sulfuric acid are taken, it will be to chlorobenzene second
Ketone is dissolved in the concentrated sulfuric acid at 0 DEG C, is added the nitration mixture previously prepared and is sufficiently mixed, and 2h is reacted.TLC detection reaction terminates
Afterwards, reaction solution is poured into 1 liter of ice water, white solid is precipitated, then be filtered under diminished pressure, collect filter cake and recrystallized, it is cold
But it is filtered under diminished pressure to obtain white crystal afterwards, arrives 3- nitro -4- chloro-acetophenone 5.6g, yield with draining after ice ethanol washing
70%.
Characterization of The Products：White crystal, m.p.298 DEG C.HNMR characterize data：1H NMR(500 MHz,CDCl3)δ8.44
(d, J=2.0Hz, 1H), 8.10 (dd, J=8.4,2.0Hz, 1H), 7.70 (d, J=8.4Hz, 1H), 2.67 (s, 3H)
(2) it takes 4g (20mmol) 3- nitro -4- chloro-acetophenone to be dissolved in 25mlDMSO solvent, is added 5.8g (24mmol)
Nine water vulcanized sodium, and react 6h at room temperature, and TLC is detected after reaction, and reaction solution is poured into a large amount of water, and filter is adjusted after filtering
Yellow solid is precipitated in the PH to 4 of liquid, and filter cake is collected after being filtered, washed and is drained to get crude product；Gained crude product again into
Row column chromatography for separation, using volume ratio for 6/1-20/1 petrol ether/ethyl acetate mixed liquor as eluant, eluent, collect chemical combination containing target
The eluent of object is dried after solvent is evaporated off to get 3- nitro -4- sulfydryl acetophenone 3.2g, yield 80%.
Characterization of The Products：Yellow solid, mass spectroscopy molecular amount are 197, HNMR characterize data：1H NMR(500MHz,CDCl3)δ
8.81 (d, J=1.9Hz, 1H), 8.03 (dd, J=8.3,1.9 Hz, 1H), 7.56 (d, J=8.3Hz, 1H), 4.25 (s, 1H),
2.66(s,3H).
(3) 2g (10mmol) 3- nitro -4- sulfydryl acetophenone and 2.3g (35mmol) Zn powder are mixed in 25ml formic acid
In, 5h is reacted at 75 DEG C.TLC is detected after reaction, reaction solution is filtered, then filtrate is rotated to one third, is then fallen
Enter in the aqueous solution of sodium carbonate, is extracted with ethyl acetate after being sufficiently stirred.It is washed with water 3 times after ethyl acetate layer is collected, so
Washed once afterwards with saturated salt solution, collect ethyl acetate layer it is dry after filter, be spin-dried for up to crude product, gained crude product again into
Row column chromatography for separation, using volume ratio for 6/1-20/1 petrol ether/ethyl acetate mixed liquor as eluant, eluent, collect chemical combination containing target
The eluent of object is dried after solvent is evaporated off to get product 1- (5- benzothiazolyl) ethyl ketone 0.9g, yield 51%.
Characterization of The Products：Faint yellow solid, mass spectroscopy molecular amount are 177, HNMR characterize data： 1H NMR(500MHz,
CDCl3) δ 9.08 (s, 1H), 8.69 (d, J=1.2Hz, 1H), 8.16-7.89 (m, 2H), 2.70 (s, 3H)
Embodiment 2
(1) concentrated nitric acid that 4ml mass fraction is 65%~68% and the concentrated sulfuric acid that 4ml mass fraction is 98% are taken, it will be dense
Nitric acid dropping is prepared into nitration mixture into the concentrated sulfuric acid.6.2g (40mmol) parachloroacetophenone and the 15ml concentrated sulfuric acid are taken, it will be to chlorobenzene second
Ketone is dissolved in the concentrated sulfuric acid at 5 DEG C, is added the nitration mixture previously prepared and is sufficiently mixed, and 0.5h is reacted.TLC detection reaction terminates
Afterwards, reaction solution is poured into 1 liter of ice water, white solid is precipitated, then be filtered under diminished pressure, collect filter cake and recrystallized, it is cold
But it is filtered under diminished pressure to obtain white crystal afterwards, arrives 3- nitro -4- chloro-acetophenone 5.4g, yield with draining after ice ethanol washing
67%.
Characterization of The Products：White crystal, m.p.298 DEG C.HNMR characterize data：1H NMR(500 MHz,CDCl3)δ8.44
(d, J=2.0Hz, 1H), 8.10 (dd, J=8.4,2.0Hz, 1H), 7.70 (d, J=8.4Hz, 1H), 2.67 (s, 3H)
(2) it takes 4g (20mmol) 3- nitro -4- chloro-acetophenone to be dissolved in 20mlDMSO solvent, is added 7.2g (30mmol)
Nine water vulcanized sodium, and react 1h at room temperature, and TLC is detected after reaction, and reaction solution is poured into a large amount of water, and filter is adjusted after filtering
Yellow solid is precipitated in the PH to 4 of liquid, and filter cake is collected after being filtered, washed and is drained to get crude product；Gained crude product again into
Row column chromatography for separation, using volume ratio for 6/1-20/1 petrol ether/ethyl acetate mixed liquor as eluant, eluent, collect chemical combination containing target
The eluent of object is dried after solvent is evaporated off to get 3- nitro -4- sulfydryl acetophenone 3g, yield 75%.
Characterization of The Products：Yellow solid, mass spectroscopy molecular amount are 197, HNMR characterize data：1H NMR(500MHz,CDCl3)δ
8.81 (d, J=1.9Hz, 1H), 8.03 (dd, J=8.3,1.9 Hz, 1H), 7.56 (d, J=8.3Hz, 1H), 4.25 (s, 1H),
2.66(s,3H).
(3) 2g (10mmol) 3- nitro -4- sulfydryl acetophenone and 1.95g (30mmol) Zn powder are mixed in 20ml formic acid
In, 1h is reacted at 110 DEG C.TLC is detected after reaction, reaction solution is filtered, then filtrate is rotated to one third, is then fallen
Enter in the aqueous solution of sodium carbonate, is extracted with ethyl acetate after being sufficiently stirred.It is washed with water 3 times after ethyl acetate layer is collected, so
Washed once afterwards with saturated salt solution, collect ethyl acetate layer it is dry after filter, be spin-dried for up to crude product, gained crude product again into
Row column chromatography for separation, using volume ratio for 6/1-20/1 petrol ether/ethyl acetate mixed liquor as eluant, eluent, collect chemical combination containing target
The eluent of object is dried after solvent is evaporated off to get product 1- (5- benzothiazolyl) ethyl ketone 0.8g, yield 45%.
Characterization of The Products：Faint yellow solid, mass spectroscopy molecular amount are 177, HNMR characterize data： 1H NMR(500MHz,
CDCl3) δ 9.08 (s, 1H), 8.69 (d, J=1.2Hz, 1H), 8.16-7.89 (m, 2H), 2.70 (s, 3H)
Embodiment 3
(1) concentrated nitric acid that 4ml mass fraction is 65%~68% and the concentrated sulfuric acid that 12ml mass fraction is 98% are taken, it will be dense
Nitric acid dropping is prepared into nitration mixture into the concentrated sulfuric acid.6.2g (40mmol) parachloroacetophenone and the 20ml concentrated sulfuric acid are taken, it will be to chlorobenzene second
Ketone is dissolved in the concentrated sulfuric acid at 5 DEG C, is added the nitration mixture previously prepared and is sufficiently mixed, and 0.5h is reacted.TLC detection reaction terminates
Afterwards, reaction solution is poured into 1 liter of ice water, white solid is precipitated, then be filtered under diminished pressure, collect filter cake and recrystallized, it is cold
But it is filtered under diminished pressure to obtain white crystal afterwards, arrives 3- nitro -4- chloro-acetophenone 5.2g, yield with draining after ice ethanol washing
65%.
Characterization of The Products：White crystal, m.p.298 DEG C.HNMR characterize data：1H NMR(500 MHz,CDCl3)δ8.44
(d, J=2.0Hz, 1H), 8.10 (dd, J=8.4,2.0Hz, 1H), 7.70 (d, J=8.4Hz, 1H), 2.67 (s, 3H)
(2) it takes 4g (20mmol) 3- nitro -4- chloro-acetophenone to be dissolved in 25mlDMF solvent, is added 7.2g (30mmol)
Nine water vulcanized sodium, and react 1h at room temperature, and TLC is detected after reaction, and reaction solution is poured into a large amount of water, and filter is adjusted after filtering
Yellow solid is precipitated in the PH to 4 of liquid, and filter cake is collected after being filtered, washed and is drained to get crude product；Gained crude product again into
Row column chromatography for separation, using volume ratio for 6/1-20/1 petrol ether/ethyl acetate mixed liquor as eluant, eluent, collect chemical combination containing target
The eluent of object is dried after solvent is evaporated off to get 3- nitro -4- sulfydryl acetophenone 2.8g, yield 70%.
Characterization of The Products：Yellow solid, mass spectroscopy molecular amount are 197, HNMR characterize data：1H NMR(500MHz,CDCl3)δ
8.81 (d, J=1.9Hz, 1H), 8.03 (dd, J=8.3,1.9 Hz, 1H), 7.56 (d, J=8.3Hz, 1H), 4.25 (s, 1H),
2.66(s,3H).
(3) 2g (10mmol) 3- nitro -4- sulfydryl acetophenone and 1.3g (20mmol) Zn powder are mixed in 30ml formic acid
In, 6h is reacted at 50 DEG C.TLC is detected after reaction, reaction solution is filtered, then filtrate is rotated to one third, is then fallen
Enter in the aqueous solution of sodium carbonate, is extracted with ethyl acetate after being sufficiently stirred.It is washed with water 3 times after ethyl acetate layer is collected, so
Washed once afterwards with saturated salt solution, collect ethyl acetate layer it is dry after filter, be spin-dried for up to crude product, gained crude product again into
Row column chromatography for separation, using volume ratio for 6/1-20/1 petrol ether/ethyl acetate mixed liquor as eluant, eluent, collect chemical combination containing target
The eluent of object is dried after solvent is evaporated off to get product 1- (5- benzothiazolyl) ethyl ketone 0.73g, yield 42%.
Characterization of The Products：Faint yellow solid, mass spectroscopy molecular amount are 177, HNMR characterize data： 1H NMR(500MHz,
CDCl3) δ 9.08 (s, 1H), 8.69 (d, J=1.2Hz, 1H), 8.16-7.89 (m, 2H), 2.70 (s, 3H)
Embodiment 4
(1) concentrated nitric acid that 4ml mass fraction is 65%~68% and the concentrated sulfuric acid that 12ml mass fraction is 98% are taken, it will
Concentrated nitric acid, which is added drop-wise in the concentrated sulfuric acid, is prepared into nitration mixture.6.2g (40mmol) parachloroacetophenone and the 25ml concentrated sulfuric acid are taken, it will be to chlorobenzene
Ethyl ketone is dissolved in the concentrated sulfuric acid at -20 DEG C, is added the nitration mixture previously prepared and is sufficiently mixed, and 1.5h is reacted.TLC detection reaction
After, reaction solution is poured into 1 liter of ice water, white solid is precipitated, then be filtered under diminished pressure, filter cake is collected and is tied again
Crystalline substance is filtered under diminished pressure to obtain white crystal after cooling, arrives 3- nitro -4- chloro-acetophenone 5.6g with draining after ice ethanol washing,
Yield 70%.
Characterization of The Products：White crystal, m.p.298 DEG C.HNMR characterize data：1H NMR(500 MHz,CDCl3)δ8.44
(d, J=2.0Hz, 1H), 8.10 (dd, J=8.4,2.0Hz, 1H), 7.70 (d, J=8.4Hz, 1H), 2.67 (s, 3H)
(2) it takes 4g (20mmol) 3- nitro -4- chloro-acetophenone to be dissolved in 20mlDMF solvent, is added 7.2g (30mmol)
Nine water vulcanized sodium, and react 1h at room temperature, and TLC is detected after reaction, and reaction solution is poured into a large amount of water, and filter is adjusted after filtering
Yellow solid is precipitated in the PH to 4 of liquid, and filter cake is collected after being filtered, washed and is drained to get crude product；Gained crude product again into
Row column chromatography for separation, using volume ratio for 6/1-20/1 petrol ether/ethyl acetate mixed liquor as eluant, eluent, collect chemical combination containing target
The eluent of object is dried after solvent is evaporated off to get 3- nitro -4- sulfydryl acetophenone 2.9g, yield 72%.
Characterization of The Products：Yellow solid, mass spectroscopy molecular amount are 197, HNMR characterize data：1H NMR(500MHz,CDCl3)δ
8.81 (d, J=1.9Hz, 1H), 8.03 (dd, J=8.3,1.9 Hz, 1H), 7.56 (d, J=8.3Hz, 1H), 4.25 (s, 1H),
2.66(s,3H).
(3) 2g (10mmol) 3- nitro -4- sulfydryl acetophenone and 1.95g (30mmol) Zn powder are mixed in 20ml formic acid
In, 3h is reacted at 80 DEG C.TLC is detected after reaction, reaction solution is filtered, then filtrate is rotated to one third, is then fallen
Enter in the aqueous solution of sodium carbonate, is extracted with ethyl acetate after being sufficiently stirred.It is washed with water 3 times after ethyl acetate layer is collected, so
Washed once afterwards with saturated salt solution, collect ethyl acetate layer it is dry after filter, be spin-dried for up to crude product, gained crude product again into
Row column chromatography for separation, using volume ratio for 6/1-20/1 petrol ether/ethyl acetate mixed liquor as eluant, eluent, collect chemical combination containing target
The eluent of object is dried after solvent is evaporated off to get product 1- (5- benzothiazolyl) ethyl ketone 0.85g, yield 48%.
Characterization of The Products：Faint yellow solid, mass spectroscopy molecular amount are 177, HNMR characterize data： 1H NMR(500MHz,
CDCl3) δ 9.08 (s, 1H), 8.69 (d, J=1.2Hz, 1H), 8.16-7.89 (m, 2H), 2.70 (s, 3H)
Embodiment 5
(1) concentrated nitric acid that 4ml mass fraction is 65%~68% and the concentrated sulfuric acid that 8ml mass fraction is 98% are taken, it will be dense
Nitric acid dropping is prepared into nitration mixture into the concentrated sulfuric acid.6.2g (40mmol) parachloroacetophenone and the 30ml concentrated sulfuric acid are taken, it will be to chlorobenzene second
Ketone is dissolved in the concentrated sulfuric acid at 5 DEG C, is added the nitration mixture previously prepared and is sufficiently mixed, and 1.5h is reacted.TLC detection reaction terminates
Afterwards, reaction solution is poured into 1 liter of ice water, white solid is precipitated, then be filtered under diminished pressure, collect filter cake and recrystallized, it is cold
But it is filtered under diminished pressure to obtain white crystal afterwards, arrives 3- nitro -4- chloro-acetophenone 5.2g, yield with draining after ice ethanol washing
65%.
Characterization of The Products：White crystal, m.p.298 DEG C.HNMR characterize data：1H NMR(500 MHz,CDCl3)δ8.44
(d, J=2.0Hz, 1H), 8.10 (dd, J=8.4,2.0Hz, 1H), 7.70 (d, J=8.4Hz, 1H), 2.67 (s, 3H)
(2) it takes 4g (20mmol) 3- nitro -4- chloro-acetophenone to be dissolved in 30mlDMSO solvent, is added 7.2g (30mmol)
Nine water vulcanized sodium, and react 1h at room temperature, and TLC is detected after reaction, and reaction solution is poured into a large amount of water, and filter is adjusted after filtering
Yellow solid is precipitated in the PH to 4 of liquid, and filter cake is collected after being filtered, washed and is drained to get crude product；Gained crude product again into
Row column chromatography for separation, using volume ratio for 6/1-20/1 petrol ether/ethyl acetate mixed liquor as eluant, eluent, collect chemical combination containing target
The eluent of object is dried after solvent is evaporated off to get 3- nitro -4- sulfydryl acetophenone 3g, yield 75%.
Characterization of The Products：Yellow solid, mass spectroscopy molecular amount are 197, HNMR characterize data：1H NMR(500MHz,CDCl3)δ
8.81 (d, J=1.9Hz, 1H), 8.03 (dd, J=8.3,1.9 Hz, 1H), 7.56 (d, J=8.3Hz, 1H), 4.25 (s, 1H),
2.66(s,3H).
(3) 2g (10mmol) 3- nitro -4- sulfydryl acetophenone and 1.95g (30mmol) Zn powder are mixed in 20ml formic acid
In, 3h is reacted at 100 DEG C.TLC is detected after reaction, reaction solution is filtered, then filtrate is rotated to one third, is then fallen
Enter in the aqueous solution of sodium carbonate, is extracted with ethyl acetate after being sufficiently stirred.It is washed with water 3 times after ethyl acetate layer is collected, so
Washed once afterwards with saturated salt solution, collect ethyl acetate layer it is dry after filter, be spin-dried for up to crude product, gained crude product again into
Row column chromatography for separation, using volume ratio for 6/1-20/1 petrol ether/ethyl acetate mixed liquor as eluant, eluent, collect chemical combination containing target
The eluent of object is dried after solvent is evaporated off to get product 1- (5- benzothiazolyl) ethyl ketone 0.8g, yield 45%.
Characterization of The Products：Faint yellow solid, mass spectroscopy molecular amount are 177, HNMR characterize data： 1H NMR(500MHz,
CDCl3) δ 9.08 (s, 1H), 8.69 (d, J=1.2Hz, 1H), 8.16-7.89 (m, 2H), 2.70 (s, 3H).
Claims (10)
- The synthetic method of 1- shown in a kind of formula IV 1. (5- benzothiazolyl) ethyl ketone, it is characterised in that：The method is specific It is prepared in accordance with the following steps：(1) parachloroacetophenone shown in Formulas I is dissolved in the concentrated sulfuric acid at -20 DEG C~5 DEG C, obtains the dense sulphur of parachloroacetophenone Then nitration mixture is added into the concentrated sulfuric acid solution of the parachloroacetophenone in acid solution, the fully reacting at -20 DEG C~10 DEG C, Reaction solution A is obtained, it is post-treated to obtain 3- nitro -4- chloro-acetophenone shown in formula II；The additional amount of the concentrated sulfuric acid is with institute The mass ratio for the parachloroacetophenone stated is 1-5ml/g；The nitration mixture is the mixed liquor of concentrated nitric acid and the concentrated sulfuric acid；The Formulas I Shown in feed intake the ratio between the amount of substance of concentrated nitric acid in parachloroacetophenone and the nitration mixture be 1:1~2；(2) 3- nitro -4- chloro-acetophenone shown in formula II obtained by step (1) is dissolved in organic solvent, nine water vulcanized sodium is added, Fully reacting at room temperature obtains reaction solution B, post-treated to obtain 3- nitro -4- sulfydryl acetophenone shown in formula III；It is described Formula II shown in 3- nitro -4- chloro-acetophenone additional amount and the ratio between the amount of nine aqueous sodium persulfate substances be 1:0.8~ 2；(3) 3- nitro -4- sulfydryl acetophenone shown in formula III obtained by step (2) is dissolved in formic acid, Zn powder is added, 50~ Fully reacting at 110 DEG C obtains reaction liquid C, post-treated to obtain 1- shown in formula IV (5- benzothiazolyl) ethyl ketone；The formula The ratio between amount of substance of 3- nitro -4- sulfydryl acetophenone shown in III and Zn powder is 1:2~1:5；
- 2. the method as described in claim 1, it is characterised in that：In step (1), the reaction temperature is 0 DEG C, the reaction time For 0.5-2h.
- 3. the method as described in claim 1, it is characterised in that：In step (1), the post-processing approach of the reaction solution A is： After reaction, reaction solution A is poured into ice water, is filtered under diminished pressure after solid is precipitated, collect filter cake and recrystallized, it is cold But it is filtered under diminished pressure to obtain crystal afterwards, with being drained after ice ethanol washing to get 3- nitro -4- chloro-acetophenone shown in the Formulas I.
- 4. the method as described in claim 1, it is characterised in that：In step (2), the organic solvent is N, N- dimethyl methyl Amide or dimethyl sulfoxide.
- 5. the method as described in claim 1, it is characterised in that：In step (2), the additional amount of the organic solvent is with II institute of formula The amount of the substance of the 3- nitro -4- chloro-acetophenone shown is calculated as 0.5~2ml/mmol.
- 6. the method as described in claim 1, it is characterised in that：In step (2), the post-processing approach of the reaction solution B is： After reaction, reaction solution B is poured into water, the PH of filtrate is adjusted after filtering to acidity, solid is precipitated, is received after being filtered, washed Collection filter cake is drained, and crude product is obtained, and the crude product is carried out column chromatography for separation, is the petroleum of 6/1-20/1 with volume ratio Ether/ethyl acetate mixtures are eluant, eluent, collect the eluent containing target compound, are dried after solvent is evaporated off to get described 3- nitro -4- sulfydryl acetophenone shown in formula III.
- 7. the method as described in claim 1, it is characterised in that：In step (3), the additional amount of the formic acid is with the formula III Shown in the amount of substance of 3- nitro -4- sulfydryl acetophenone be calculated as 1~3ml/mmol.
- 8. the method as described in claim 1, it is characterised in that：In step (3), the reaction temperature is 75 DEG C, when reaction Between be 1~5h.
- 9. the method as described in claim 1, it is characterised in that：In step (3), the post-processing approach of the reaction liquid C is： After reaction, first reaction liquid C is filtered, then filtrate is rotated to one third, be subsequently poured into the aqueous solution of sodium carbonate, fill It is extracted with ethyl acetate after dividing stirring, is washed with water after ethyl acetate layer is collected 3 times, then uses saturated common salt water washing one It is secondary, it filters, be spin-dried for up to crude product after collection ethyl acetate layer is dry, gained crude product carries out column chromatography for separation again, with volume Than being eluant, eluent for the petrol ether/ethyl acetate mixed liquor of 6/1-20/1, the eluent containing target compound is collected, solvent is evaporated off It dries afterwards to get target product 1- (5- benzothiazolyl) ethyl ketone.
- 10. the method as described in one of claim 1~9, it is characterised in that：The method specifically in accordance with the following steps into Row：(1) it by parachloroacetophenone shown in Formulas I at 0 DEG C, is dissolved in the concentrated sulfuric acid solvent that mass fraction is 98%, obtains to chlorine Then nitration mixture is added into the concentrated sulfuric acid solution of the parachloroacetophenone in the concentrated sulfuric acid solution of acetophenone, carry out at 0 DEG C anti- 0.5-2h is answered, reaction solution A is obtained after fully reacting, it is post-treated to obtain 3- nitro -4- chloro-acetophenone shown in formula II；Described The additional amount of the concentrated sulfuric acid is 1-5ml/g with the mass ratio of the parachloroacetophenone；The nitration mixture is that volume ratio is 1：1.5 Mass fraction be 65%~68% concentrated nitric acid and mass fraction be 98% the concentrated sulfuric acid mixed liquor；Shown in the Formulas I Parachloroacetophenone and the nitration mixture in feed intake the ratio between the amount of substance of concentrated nitric acid be 1:1.5；(2) 3- nitro -4- chloro-acetophenone shown in formula II obtained by step (1) is dissolved in organic solvent, the vulcanization of nine water is added Sodium reacts 1-6h at room temperature, obtains reaction solution B, post-treated to obtain 3- nitro -4- sulfydryl acetophenone shown in formula III；Institute The ratio between the additional amount of 3- nitro -4- chloro-acetophenone and the amount of nine aqueous sodium persulfate substances shown in the formula II stated are 1:1.2； The additional amount of the organic solvent is calculated as 0.5~2ml/mmol with the amount of the substance of 3- nitro -4- chloro-acetophenone shown in formula II；(3) 3- nitro -4- sulfydryl acetophenone shown in formula III obtained by step (2) is dissolved in formic acid, adds Zn powder, adds Heat obtains reaction liquid C to 75 DEG C of 1~5h of reaction, post-treated to obtain 1- shown in formula IV (5- benzothiazolyl) ethyl ketone；It is described The ratio between amount of substance of 3- nitro -4- sulfydryl acetophenone shown in formula III and Zn powder is 1：3.5；The additional amount of the formic acid with The amount of the substance of 3- nitro -4- sulfydryl acetophenone shown in the formula III is calculated as 1~3ml/mmol.
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