CN108358868A - 2- replaces the novel processing step of benzothiazole compound - Google Patents
2- replaces the novel processing step of benzothiazole compound Download PDFInfo
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- CN108358868A CN108358868A CN201810342647.0A CN201810342647A CN108358868A CN 108358868 A CN108358868 A CN 108358868A CN 201810342647 A CN201810342647 A CN 201810342647A CN 108358868 A CN108358868 A CN 108358868A
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- toluene
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- 0 C(*=CC=C1)C2=C1SC(/C1=C\C/C=C/C/C=C1)N2 Chemical compound C(*=CC=C1)C2=C1SC(/C1=C\C/C=C/C/C=C1)N2 0.000 description 1
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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
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
- C07D277/66—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 with aromatic rings or ring systems directly attached in position 2
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Abstract
The present invention provides a kind of novel processing steps of 2 substitution benzothiazole compound, are related to synthetic organic chemical art.Novel processing step provided by the invention generates 2 substitution benzothiazole compounds in the presence of catalyst, oxidant and additive, using toluene or derivatives thereof by free radical reaction course and near amino thiophenols single step reaction.For example and without limitation, scheme provided by the invention, advantage are：The present invention makes toluene or derivatives thereof and near amino thiophenols generate 2 substitution benzothiazoles by building C S keys and the coupling of one step of C N keys using free based method for the first time, with many advantages, such as efficient, succinct, environmental-friendly, raw material is easy to get, product purity is high, there are good application value and Research Prospects.
Description
Technical field
The invention belongs to synthetic organic chemical arts, and in particular to a kind of novel system of 2- substitutions benzothiazole compound
Preparation Method.
Background technology
Benzothiazole compound is that secondary metabolism produces in organism as a kind of very important nitrogen-containing heterocycle compound
The common structural unit of object, while being also a kind of dicyclic compound with pharmaceutical activity.Due to sulphur atom have kill bacterium,
The characteristics such as fluorescence radiation, therefore benzothiazole and its derivative not only have extremely important work in terms of biological medicine, agricultural
With, such as in agriculture field, benzothiazole compound has anti-phytoviral activity, insecticidal activity, activity of weeding and inhibition
The characteristic of plant cell division and be widely used agriculturally；In field of medicaments, clinical medicine proves benzothiazoles medicine
Object has the function of anticancer, antibacterial, antiviral, anti-inflammatory and antitumor etc..In addition, benzothiazole compound in fluorescence analysis and
Organometallic chemistry field is widely used.Benzothiazole compound structure is easy to be modified simultaneously, can be used as chemistry
Intermediate participates in the synthesis of complicated organic matter.
2- replaces the synthetic method of benzothiazole very much, mainly carries out intermolecular coupling as raw material using aromatic aldehyde, acid anhydrides, or
Person carries out intramolecular coupling cyclization formation by raw material of adjacent halogen thioamides.The above method is in spite of its feature and certain
Potential using value, but since there is wherein many methods raw material to be not easy to obtain, severe reaction conditions, post-treatment condition are cumbersome etc.
Disadvantage, therefore limit the application of these methods.
Invention content
It is an object of the present invention to overcome the deficiencies of the prior art and provide a kind of 2- substitution benzothiazole compound
Novel processing step.
The present invention utilizes toluene or derivatives thereof directly to make by Radical Addition near amino thiophenols for the first time
sp3C-H activation structure C-S keys and C-N keys, one-step synthesis go out 2- substitution benzothiazole compounds, have abandoned in conventional method
Utilize the defect that unstable aldehydes and anhydride are raw material.The present invention is directly replaced using toluene or derivatives thereof to synthesize 2-
Benzothiazole compound, catalytic activity is high in reaction process, condition is relatively mild, atom utilization is high, meets greenization scientific principle
It reads；Meanwhile the raw material used is easy to get being dirt cheap on the market, reaction process is easy to operate.
In order to realize above-mentioned target, the present invention provides following technical solutions：
Using toluene or derivatives thereof (II) and near amino thiophenols in mantoquita as catalyst, pyrovinic acid existence condition
Under, mono- steps of 18-24h are reacted at 120 DEG C with di-t-butyl peroxide (DTBP) generates 2- substitution benzothiazole compounds
(I), reaction equation (1) is：
Wherein：
R=hydrogen, fluorine, chlorine, bromine are one or more of in methyl or phenyl.
Further, the novel processing step of 2- substitutions benzothiazole compound provided by the invention, is as follows：
By 0.06mmol copper salt catalysts, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL toluene or derivatives thereof, are flowed back 20 hours at 120 DEG C；It is cooling after reaction is completed
To room temperature, reaction mixture is diluted with the ethyl acetate of 30mL, then uses the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3
Solution, the washing of 8mL saturated common salt aqueous solutions, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column layer
Analyse (petrol ether/ethyl acetate) isolated product.
In a preferred embodiment, the copper salt catalyst is cuprous oxide or cuprous iodide or copper acetate or chlorine
Change cuprous；It is further preferred that the copper salt catalyst is cuprous oxide.
In a preferred embodiment, described toluene or derivatives thereof is 4- toluene fluorides or 4- chlorotoluenes or 4- bromine first
Benzene or 2- methyl naphthalenes or 2- methyl toluenes or 4- methyl toluenes or 3,5- dimethyl toluene or 3.4- dichlorotoleune or 3-
Toluene fluoride or 2- toluene fluorides or 3- chlorotoluenes or 3- toluene bromides.
The present invention has reaction process succinct, and post-processing is simple, and environmentally protective, raw material is easy to get, and comprehensive yield is higher to wait spies
Point.
Further to understand fully the mechanism of the reaction：First, when use 0.06mmol cuprous oxide for catalyst, 0.3mmol
In the presence of pyrovinic acid, reacted in 120 DEG C of Toluenes and near amino thiophenols with 1.2mmol di-t-butyl peroxides (DTBP)
The yield highest of the obtained 2- phenylbenzothiazols of 20h, and experimentation is easy to operate, by-product is less, therefore we are just
It is " optimum experimental condition " to select the condition.
The present invention has carried out following experiment：When just starting, the present invention speculates toluene initial oxidation into benzaldehyde, and benzaldehyde is again
It is reacted near amino thiophenols and generates benzothiazole.In order to confirm the supposition of the present invention, the benzaldehyde and 0.3mmol of 2mL are allowed
Near amino thiophenols are reacted under " optimum experimental condition ", and chemical formula (2) is as follows：
The yield of 2- phenylbenzothiazols is 0%.Therefore can negate it is of the present invention reaction be by benzaldehyde this
Intermediate steps.
Further, it is a free radical process that the present invention, which speculates that toluene and near amino thiophenols reaction generate benzothiazole,.
In order to confirm that some following experiments have been done in the supposition, the present invention：
When the 2,2,6,6- tetramethyl piperidine oxides (TEMPO) of 0.3mmol are added in we under " optimum experimental condition "
After the TEMPO of 0.6mmol, reaction yield is respectively 61% and 37%, when the amount of TEMPO increases to 0.9mmol, no production
Object generates, and reaction equation (3) is as follows：
Since 2,2,6,6- tetramethyl piperidine oxides (TEMPO) are a kind of free radical quenchers, when being separately added into
When 0.3mmol, 0.6mmol TEMPO, reaction yield is gradually reduced, and when 0.9mmol is added, reaction does not occur, therefore demonstrate,proves
The reaction of the real present invention experienced a free radical process really when occurring.
In order to prove the fracture of methyl C-H on toluene be reaction rate determining step it is rapid, we are by the deuterium of the toluene of 1mL and 1mL
It for toluene, is blended under " optimum experimental condition " and reacts near amino thiophenols, reaction equation (4) is as follows：
Pass through1HNMR (Fig. 1) analysis shows, by the product of reaction equation (4) and the 2- phenylbenzothiazols of standard1HNMR
It is found that the 2- phenylbenzothiazols of standard should have 3.00 in the sections 7.58-7.46ppm after spectrogram (Fig. 2) comparison
Hydrogen, but the product of reaction equation (4) but has 2.62, therefore product 2- phenylbenzothiazols and the deuterated methylbenzothiazoles of 2-
The ratio between rate is 6.8:1, this indicates that the rate determining step reacted when the c h bond fracture of benzyl is rapid.
In order to understand fully an intermediate of reaction experience, we just try to make 2- (benzylthio) aniline compound (possible
Reaction intermediate) it is reacted under " optimum experimental condition ", final result obtains 65% 2- phenylbenzothiazols, reaction equation
(5) as follows：
Reaction equation (5) illustrates the intermediate provided by the invention for reacting and have passed through 2- (benzylthio) aniline.
It is tested by the analogy of above series of it is found that novel processing step provided by the invention, reaction mechanism are as follows
(as shown in Figure 2)：
(a) first as the DTBP of radical initiator by Cu+Fracture is divided into tert-butoxy free radical I and Cu+It is aoxidized
At Cu2+With tert-butoxy conjugate II；
(b) tert-butoxy free radical obtains a hydrogen from toluene becomes tert-butyl hydroperoxide, and toluene is changed into benzene
Methyl free radicals III；Benzyl radical II I can both be coupled to product 6 with itself, can also participate in subsequent reaction.
(c) compound II is combined near amino thiophenols generates metal complex IV；
(d) before generate benzyl radical II I combined with metal complex IV to be formed 2- (benzylthio) aniline 5 (lead to
Crossing reaction equation (5), we can determine whether reactions have passed through midbody compound 5 really)；2- (benzylthio) aniline 5 in mantoquita and
In the presence of DTBP, the carbon atom adjacent with sulphur loses a hydrogen and obtains intermediate V, then by single electron transfer process, further
Oxidation forms compound VI, then nitrogen-atoms attack, and intramolecular cyclization occurs and forms VII, is generated most finally by DTBP oxidations
Whole product benzothiazole.
Compared with prior art, the beneficial effects of the present invention are：The present invention is directly by toluene or derivatives thereof come one
It walks and synthesizes 2- substitution benzothiazole compounds, catalytic activity is high, condition is relatively mild in reaction process, atom utilization height, accords with
Close green chemical concept；Meanwhile the raw material used is easy to get being dirt cheap on the market, reaction process is easy to operate.
Description of the drawings
Fig. 1 is mixed with deuterated toluene for toluene provided by the invention and near amino thiophenols institute under " optimum experimental condition "
Obtain product nuclear-magnetism figure；
Fig. 2 is the 2- phenylbenzothiazol nuclear-magnetism figures of standard provided by the invention；
Fig. 3 is the reaction mechanism schematic diagram of novel processing step provided by the invention.
Specific implementation mode
With reference to specific embodiment, the present invention is further illustrated.
Reaction raw materials such as toluene used in following each embodiments or derivatives thereof (II) and near amino thiophenols etc.
Can conveniently it buy.
Following each embodiments are to enable those skilled in the art to be better understood from the present invention, but the present invention's is interior
Appearance is not limited to illustrated embodiment.
Embodiment 1
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL toluene, are flowed back 20 hours at 120 DEG C.It after reaction is completed, is cooled to room temperature, reacts
Mixture is diluted with the ethyl acetate of 30mL, then uses the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3Solution, 8mL are full
It is washed with common salt aqueous solution, then uses anhydrous Na2SO4It is dry, filter, be spin-dried for, finally use thin-layer chromatography or column chromatography (petroleum ether/
Ethyl acetate) isolated product 45.6mg, yield 72%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.09 (dd, J=8.7,
4.5Hz, 3H), 7.90 (d, J=7.9Hz, 1H), 7.52-7.46 (m, 4H), 7.38 (t, J=7.6Hz, 1H)13C NMR
(101MHz,CDCl3,25℃,TMS):δ=168.07,154.15,135.07,133.64,130.97,129.02,127.57,
126.32,125.19,123.24,121.62.HRMS(ESI):calculated for C13H10NS(M+H)+:212.0528,
found:212.0540.
Embodiment 2
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous iodides, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL toluene, are flowed back 20 hours at 120 DEG C.It after reaction is completed, is cooled to room temperature, reacts
Mixture is diluted with the ethyl acetate of 30mL, then uses the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3Solution, 8mL are full
It is washed with common salt aqueous solution, then uses anhydrous Na2SO4It is dry, filter, be spin-dried for, finally use thin-layer chromatography or column chromatography (petroleum ether/
Ethyl acetate) isolated product 31.7mg, yield 50%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.09 (dd, J=8.7,
4.5Hz, 3H), 7.90 (d, J=7.9Hz, 1H), 7.52-7.46 (m, 4H), 7.38 (t, J=7.6Hz, 1H)13C NMR
(101MHz,CDCl3,25℃,TMS):δ=168.07,154.15,135.07,133.64,130.97,129.02,127.57,
126.32,125.19,123.24,121.62.HRMS(ESI):calculated for C13H10NS(M+H)+:212.0528,
found:212.0540.
Embodiment 3
One kind replacing benzothiazole compound (2- phenylbenzothiazols) by toluene and derivative one-step synthesis 2-
Method includes the following steps：
By 0.06mmol copper acetates, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides and 0.3mmol
Pyrovinic acid is added in 2mL toluene, is flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room temperature, reaction mixture
It is diluted with the ethyl acetate of 30mL, then uses the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3Solution, 8mL saturated common salts
Aqueous solution washs, then uses anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography (petroleum ether/acetic acid second
Ester) isolated product 38.6mg, yield 61%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.09 (dd, J=8.7,
4.5Hz, 3H), 7.90 (d, J=7.9Hz, 1H), 7.52-7.46 (m, 4H), 7.38 (t, J=7.6Hz, 1H)13C NMR
(101MHz,CDCl3,25℃,TMS):δ=168.07,154.15,135.07,133.64,130.97,129.02,127.57,
126.32,125.19,123.24,121.62.HRMS(ESI):calculated for C13H10NS(M+H)+:212.0528,
found:212.0540.
Embodiment 4
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol stannous chlorides, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL toluene, are flowed back 20 hours at 120 DEG C.It after reaction is completed, is cooled to room temperature, reacts
Mixture is diluted with the ethyl acetate of 30mL, then uses the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3Solution, 8mL are full
It is washed with common salt aqueous solution, then uses anhydrous Na2SO4It is dry, filter, be spin-dried for, finally use thin-layer chromatography or column chromatography (petroleum ether/
Ethyl acetate) isolated product 34.8mg, yield 55%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.09 (dd, J=8.7,
4.5Hz, 3H), 7.90 (d, J=7.9Hz, 1H), 7.52-7.46 (m, 4H), 7.38 (t, J=7.6Hz, 1H)13C NMR
(101MHz,CDCl3,25℃,TMS):δ=168.07,154.15,135.07,133.64,130.97,129.02,127.57,
126.32,125.19,123.24,121.62.HRMS(ESI):calculated for C13H10NS(M+H)+:212.0528,
found:212.0540.
Embodiment 5
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL 4- toluene fluorides, are flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room
Temperature, reaction mixture are diluted with the ethyl acetate of 30mL, then use the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3It is molten
Liquid, the washing of 8mL saturated common salt aqueous solutions, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography
(petrol ether/ethyl acetate) isolated product 50.7mg, yield 80%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.12-8.00 (m, 3H),
7.88 (d, J=7.9Hz, 1H), 7.48 (t, J=7.7Hz, 1H), 7.37 (t, J=8.0Hz, 1H), 7.17 (t, J=8.6Hz,
2H).13C NMR(101MHz,CDCl3,25℃,TMS):δ=166.72,165.68,163.18,154.08,135.04,
129.55,126.40,125.23,123.18,121.60,116.03.HRMS(ESI):calculated for C13H9FNS(M+
H)+:230.0434,found:230.0431.
Embodiment 6
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL4- chlorotoluenes, are flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room temperature,
Reaction mixture is diluted with the ethyl acetate of 30mL, then uses the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3Solution,
8mL saturated common salt aqueous solutions wash, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography (stone
Oily ether/ethyl acetate) isolated product 56.6mg, yield 77%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.04 (dd, J=16.8,
8.3Hz, 3H), 7.90 (d, J=8.0Hz, 1H), 7.48 (dd, J=10.8,8.5Hz, 3H), 7.40 (t, J=7.6Hz, 1H)
.13C NMR(101MHz,CDCl3,25℃,TMS):δ=166.62,154.05,137.03,135.04,132.10,129.27,
128.71,126.48,125.41,123.29,121.65.HRMS(ESI):calculated for C13H9ClNS(M+H)+:
246.0139,found:246.0168.
Embodiment 7
One kind replacing benzothiazole compound (2- (4- bromophenyls) benzo thiophene by toluene and derivative one-step synthesis 2-
Azoles) method, include the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL 4- toluene bromides, are flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room
Temperature, reaction mixture are diluted with the ethyl acetate of 30mL, then use the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3It is molten
Liquid, the washing of 8mL saturated common salt aqueous solutions, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography
(petrol ether/ethyl acetate) isolated product 54.8mg, yield 63%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.06 (d, J=8.1Hz,
1H), 7.95 (d, J=8.5Hz, 2H), 7.89 (d, J=7.9Hz, 1H), 7.62 (d, J=8.5Hz, 2H), 7.50 (t, J=
7.7Hz, 1H), 7.39 (t, J=7.6Hz, 1H)13C NMR(101MHz,CDCl3,25℃,TMS):δ=166.67,154.05,
135.02,132.52,132.21,128.88,126.49,125.43,125.40,123.30,121.65.HRMS(ESI):
calculated for C13H9BrNS(M+H)+:289.9634,found:289.9627.
Embodiment 8
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL 2- methyl naphthalenes, are flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room
Temperature, reaction mixture are diluted with the ethyl acetate of 30mL, then use the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3It is molten
Liquid, the washing of 8mL saturated common salt aqueous solutions, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography
(petrol ether/ethyl acetate) isolated product 27.4mg, yield 35%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.57 (s, 1H), 8.21
(dd, J=8.6,1.6Hz, 1H), 8.12 (d, J=8.1Hz, 1H), 7.95 (q, J=8.0,7.2Hz, 3H), 7.90-7.86 (m,
1H), 7.58-7.48 (m, 3H), 7.40 (t, J=7.6Hz, 1H)13C NMR(101MHz,CDCl3,25℃,TMS):δ=
168.12,154.24,135.13,134.61,133.19,130.99,128.82,127.87,127.59,127.46,126.88,
126.39,125.25,124.44,123.24,121.64.HRMS(ESI):calculated for C17H12NS(M+H)+:
262.0685,found:262.0666.
Embodiment 9
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL2- methyl toluenes, are flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room
Temperature, reaction mixture are diluted with the ethyl acetate of 30mL, then use the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3It is molten
Liquid, the washing of 8mL saturated common salt aqueous solutions, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography
(petrol ether/ethyl acetate) isolated product 29.7mg, yield 44%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.10 (d, J=8.1Hz,
1H), 7.93 (d, J=7.9Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 7.51 (t, J=7.7Hz, 1H), 7.43-7.29 (m,
4H),2.66(s,3H).13C NMR(101MHz,CDCl3,25℃,TMS):δ=167.98,153.77,137.23,135.58,
133.07,131.51,130.52,129.98,126.11,125.07,123.36,121.34,21.33.HRMS(ESI):
calculated for C14H12NS(M+H)+:226.0685,found:226.0693.
Embodiment 10
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL4- methyl toluenes, are flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room
Temperature, reaction mixture are diluted with the ethyl acetate of 30mL, then use the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3It is molten
Liquid, the washing of 8mL saturated common salt aqueous solutions, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography
(petrol ether/ethyl acetate) isolated product 35.8mg, yield 53%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.06 (d, J=8.1Hz,
1H), 7.98 (d, J=8.1Hz, 2H), 7.89 (d, J=8.0Hz, 1H), 7.52-7.45 (m, 1H), 7.40-7.34 (m, 1H),
7.30 (d, J=7.9Hz, 2H), 2.42 (s, 3H)13C NMR(101MHz,CDCl3,25℃,TMS):δ=168.24,
154.16,141.42,134.94,130.95,129.71,127.48,126.23,124.99,123.04,121.55,
21.52.HRMS(ESI):calculated for C14H12NS(M+H)+:226.0685,found:226.0674.
Embodiment 11
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added to 2mL 3, in 5- dimethyl toluene, flow back 20 hours at 120 DEG C.It is cooling after reaction is completed
To room temperature, reaction mixture is diluted with the ethyl acetate of 30mL, then uses the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3
Solution, the washing of 8mL saturated common salt aqueous solutions, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column layer
Analyse (petrol ether/ethyl acetate) isolated product 29.3mg, yield 41%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.07 (d, J=8.1Hz,
1H), 7.89 (d, J=8.0Hz, 1H), 7.71 (s, 2H), 7.48 (t, J=7.7Hz, 1H), 7.37 (t, J=7.6Hz, 1H),
7.12(s,1H),2.40(s,6H).13C NMR(101MHz,CDCl3,25℃,TMS):δ=168.57,154.10,138.72,
134.99,133.44,132.75,126.24,125.34,125.04,123.10,121.57,21.22.HRMS(ESI):
calculated for C15H14NS(M+H)+:240.0841,found:240.0844.
Embodiment 12
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added to 2mL 3, in 4- dichlorotoleune, flow back 20 hours at 120 DEG C.After reaction is completed, it is cooled to
Room temperature, reaction mixture are diluted with the ethyl acetate of 30mL, then use the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3It is molten
Liquid, the washing of 8mL saturated common salt aqueous solutions, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography
(petrol ether/ethyl acetate) isolated product 50.4mg, yield 60%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.19 (s, 1H), 8.06
(d, J=8.1Hz, 1H), 7.92-7.84 (m, 2H), 7.56-7.48 (m, 2H), 7.44-7.38 (m, 1H)13C NMR
(101MHz,CDCl3,25℃,TMS):δ=165.03,153.91,135.07,133.42,130.95,129.01,126.65,
125.71,123.54,121.70.HRMS(ESI):calculated for C13H8NSCl2(M+H)+:279.9749,found:
279.9739.
Embodiment 13
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL 3- toluene fluorides, are flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room
Temperature, reaction mixture are diluted with the ethyl acetate of 30mL, then use the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3It is molten
Liquid, the washing of 8mL saturated common salt aqueous solutions, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography
(petrol ether/ethyl acetate) isolated product 48.4mg, yield 70%.
Product data：White solid.1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.08 (d, J=8.1Hz,
1H), 7.89 (d, J=8.0Hz, 1H), 7.86-7.79 (m, 2H), 7.53-7.37 (m, 3H), 7.21-7.14 (m, 1H)13C
NMR(101MHz,CDCl3,25℃,TMS):δ=166.48,164.28,161.82,153.97,135.72,135.64,
135.09,130.66,130.58,126.52,125.55,123.45,123.30,121.68,117.93,117.71,114.43,
114.20,58.45,53.43,18.43.HRMS(ESI):calculated for C13H8NSNaF(M+Na)+:252.0254,
found:252.0269.
Embodiment 14
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL 2- toluene fluorides, are flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room
Temperature, reaction mixture are diluted with the ethyl acetate of 30mL, then use the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3It is molten
Liquid, the washing of 8mL saturated common salt aqueous solutions, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography
(petrol ether/ethyl acetate) isolated product 44.1mg, yield 64%.
Product data：1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.42 (td, J=7.7,1.5Hz, 1H),
8.13 (d, J=8.2Hz, 1H), 7.95 (d, J=8.0Hz, 1H), 7.56-7.38 (m, 3H), 7.31 (t, J=7.6Hz, 1H),
7.28–7.23(m,1H).13C NMR(101MHz,CDCl3,25℃,TMS):δ=161.80,161.12,161.06,159.28,
152.53,135.76,135.68,132.18,132.09,129.73,126.31,125.30,124.67,123.27,121.47,
121.37,116.50,116.28.HRMS(ESI):calculated for C13H10NSNa(M+Na)+:252.0254,found:
252.0263.
Embodiment 15
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL3- chlorotoluenes, are flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room temperature,
Reaction mixture is diluted with the ethyl acetate of 30mL, then uses the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3Solution,
8mL saturated common salt aqueous solutions wash, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography (stone
Oily ether/ethyl acetate) isolated product 44.8mg, yield 61%.
Product data：1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.12 (s, 1H), 8.08 (d, J=8.2Hz,
1H), 7.93 (dd, J=12.2,7.7Hz, 2H), 7.51 (t, J=7.7Hz, 1H), 7.48-7.39 (m, 3H)13C NMR
(101MHz,CDCl3,25℃,TMS):δ=166.30,153.97,135.26,135.16,135.08,130.86,130.26,
127.41,126.55,125.69,125.57,123.45,121.69.HRMS(ESI):calculated for C13H9NSCl(M
+H)+:246.0139,found:246.0123.
Embodiment 16
A kind of novel processing step of 2- substitutions benzothiazole compound, includes the following steps：
By 0.06mmol cuprous oxide, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides, and
0.3mmol pyrovinic acids are added in 2mL3- toluene bromides, are flowed back 20 hours at 120 DEG C.After reaction is completed, it is cooled to room temperature,
Reaction mixture is diluted with the ethyl acetate of 30mL, then uses the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3Solution,
8mL saturated common salt aqueous solutions wash, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography (stone
Oily ether/ethyl acetate) isolated product 51.3mg, yield 59%.
Product data：1H NMR(400MHz,CDCl3,25℃,TMS):δ=8.27 (s, 1H), 8.08 (d, J=8.1Hz,
1H), 7.98 (d, J=7.8Hz, 1H), 7.91 (d, J=8.0Hz, 1H), 7.61 (d, J=8.0Hz, 1H), 7.51 (t, J=
7.7Hz, 1H), 7.38 (dt, J=20.5,7.6Hz, 2H)13C NMR(101MHz,CDCl3,25℃,TMS):δ=166.15,
153.96,135.48,135.08,133.78,130.49,130.26,126.55,126.15,125.57,123.44,123.18,
121.69.HRMS(ESI):calculated for C13H9NSBr(M+H)+:289.9634,found:289.9627.
Foregoing description is only the description to present pre-ferred embodiments, is not any restriction to the scope of the invention.Appoint
Any change or modification what those skilled in the art makes according to the technology contents of the disclosure above should all regard
For equivalent effective embodiment, the range of technical solution of the present invention protection is belonged to.
Claims (5)
1. a kind of novel processing step of 2- substitutions benzothiazole compound, it is characterised in that：By toluene or derivatives thereof
(II) near amino thiophenols in mantoquita as catalyst, under pyrovinic acid existence condition, with di-t-butyl peroxide (DTBP)
Mono- steps of 18-24h are reacted at 120 DEG C and generate 2- substitution benzothiazole compounds (I), and reaction equation (1) is：
Wherein：
R=hydrogen, fluorine, chlorine, bromine are one or more of in methyl or phenyl.
2. the novel processing step of 2- substitutions benzothiazole compound according to claim 1, which is characterized in that specific
Steps are as follows：
By 0.06mmol copper salt catalysts, 0.3mmol near amino thiophenols, 1.2mmol di-t-butyl peroxides and 0.3mmol
Pyrovinic acid is added in 2mL toluene or derivatives thereof, is flowed back 20 hours at 120 DEG C；After reaction is completed, it is cooled to room temperature,
Reaction mixture is diluted with the ethyl acetate of 30mL, then uses the NaHSO of the saturated salt solution of 8mL, 8mL respectively successively3Solution,
8mL saturated common salt aqueous solutions wash, then use anhydrous Na2SO4It is dry, it filters, is spin-dried for, finally use thin-layer chromatography or column chromatography (stone
Oily ether/ethyl acetate) isolated product.
3. the novel processing step of 2- substitutions benzothiazole compound according to claim 2, it is characterised in that：It is described
Copper salt catalyst is cuprous oxide or cuprous iodide or copper acetate or stannous chloride.
4. the novel processing step of 2- substitutions benzothiazole compound according to claim 3, it is characterised in that：It is described
Copper salt catalyst is cuprous oxide.
5. the novel processing step of 2- substitutions benzothiazole compound according to claim 2, it is characterised in that：It is described
Toluene derivative is 4- toluene fluorides or 4- chlorotoluenes or 4- toluene bromides or 2- methyl naphthalenes or 2- methyl toluenes or 4- methyl first
Benzene or 3,5- dimethyl toluene or 3.4- dichlorotoleune or 3- toluene fluorides or 2- toluene fluorides or 3- chlorotoluenes or 3- bromine first
Benzene.
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| CN113979966A (en) * | 2021-11-16 | 2022-01-28 | 聊城大学 | Preparation method of 2-phenylbenzothiazole |
| CN115504942A (en) * | 2022-09-15 | 2022-12-23 | 汕头大学 | Synthesis method of alkyl or acyl substituted benzothiazole derivative |
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