CN110156716A - A kind of synthetic method of benzothiazole ester derivative - Google Patents
A kind of synthetic method of benzothiazole ester derivative Download PDFInfo
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- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
The present invention provides a kind of synthetic methods of benzothiazole ester derivative, it is characterized in that, it include: under mixing condition, benzothiazole derivant shown in formula I, organic carboxyl acid, copper catalyst and silver salt are heated to reaction in organic solvent, the benzothiazole ester derivative as shown in formula II is obtained, X is the ester group in the organic carboxyl acid in formula II；Wherein, R1For H or 6-OCH3；R2For 2 '-CH3、3′‑CH3,4′-Cl.This method carries out in air atmosphere, at low cost, does not have to use highly toxic substrate or organic solvent, does not also need your catalyst such as precious metal palladium, and the raw material in the present invention is easy to get, and synthesis step is simple, and side reaction is few, and target product yield is high, and promotional value is high.
Description
Technical field
The invention belongs to organic synthesis fields, and in particular, to a kind of synthetic method of benzothiazole ester derivative.
Background technique
Benzothiazole compound is widely present in natural prodcuts, because it is with good biology and physiological activity, and
It is widely used in pesticide, pharmaceuticals industry etc..It industrially, is the raw material for preparing fluorescent dye, fluorescent whitening agent, medicine
On, for the treatment of the diseases such as tumour, rheumatoid arthritis and the detection of a variety of bacterial strains and cancerous cell line.Because it is in life
It produces, the application value that field of medicaments is important, it is particularly important to the research of its synthetic method.
Reported in document synthesis benzothiazole compound method mainly include the following types:
(1) 2013 year, Wu seminar reported with Pd (OAc)2Catalyzing aromatic hydrocarbon ortho position C (sp2)-H be acylated experiment side
Case.(2) the same year, Ding seminar have developed the reaction that the ortho position of palladium chtalyst aromatic hydrocarbons is acylated.(3) 2014 years, Kuang project
Group has developed the reaction of palladium chtalyst 1,2,3- triazole class compounds ortho position acyloxylation.(4) 2015 years, Patel seminar passed through
Catalyst Pd (OAc)2, oxidant ammonium ceric nitrate (CAN) realizes benzothiazole ester derivative ortho position and ester, fragrant oxygen occurs
The reaction of base.(5) 2017 years, Chakraborti was additive using NHPI, with Pd (II)-catalytic activation C (sp2)-H
Key realizes the arylation that heterocyclic skeleton intersects dehydrogenation coupling (CDC) with arylmethane.
In conclusion in conclusion there are many method of prior art synthesis benzothiazole ester derivative compound, still
Some needs of these methods are by complicated synthesis step and side reaction is more and yield is relatively low；Some use highly toxic bottom
Object or organic solvent easily cause environmental pollution；Some are catalyst using precious metal palladium etc., and cost costly, is not suitable for work
The disadvantages of industry produces.Therefore it provides a kind of novel green synthesis method for synthesizing benzothiazole ester derivative is necessary.
Summary of the invention
It is not deposited for solution is existing in the prior art, the present invention provides a kind of conjunctions for synthesizing benzothiazole ester derivative
At method, using silver salt as oxidant, cheap copper catalyst such as (copper acetate, copper sulphate, cuprous bromide, cuprous oxide and iodine
Change one of cuprous or a variety of) catalysis benzothiazole derivant reacted in organic solvent with organic carboxyl acid, benzene can be obtained
And thiazole ester derivative, without also not needing using highly toxic substrate or organic solvent, precious metal palladium etc. is expensive to urge this method
Agent, the raw material in the present invention are easy to get, and synthesis step is simple, and side reaction is few, and target product yield is high, and promotional value is high.
To achieve the goals above, the present invention provides a kind of synthetic methods of benzothiazole ester derivative, comprising:
Under mixing condition, benzothiazole derivant shown in formula I, organic carboxyl acid, copper catalyst and silver salt are heated in organic solvent
Reaction, obtains the benzothiazole ester derivative as shown in formula II, and X is the ester group in the organic carboxyl acid in formula II；
Wherein, R1For H or 6-OCH3；R2
For 2 '-CH3、3′-CH3、4′-Cl。
Through the above technical solutions, all existing for benzothiazole ester derivative the present invention overcomes synthesizing in the prior art
More defects provide a kind of synthetic method for synthesizing benzothiazole ester derivative, using silver salt as oxidant, cheap copper catalysis
Agent such as (one of copper acetate, copper sulphate, cuprous bromide, cuprous oxide and cuprous iodide or a variety of) is catalyzed benzothiazole and spreads out
Biology reacts in organic solvent with organic carboxyl acid, and benzothiazole ester derivative can be obtained.Compared with prior art, this hair
It is bright to have the advantage that (1) carries out in air atmosphere, it is at low cost；(2) not using noble metals such as palladium, rutheniums, but oxidation is utilized
It is cuprous etc. to make catalyst, save the cost；(3) reaction raw materials are cheap and are easy to get；(4) synthetic method is high-efficient, and use scope is wide,
It is suitble to a variety of substrate reactions.This method carries out in air atmosphere, at low cost, does not have to use highly toxic substrate or organic molten
Agent does not need your catalyst such as precious metal palladium yet, and the raw material in the present invention is easy to get, and synthesis step is simple, and side reaction is few, and target produces
Produce rate is high, and promotional value is high.
Other features and advantages of the present invention will the following detailed description will be given in the detailed implementation section.
Detailed description of the invention
The drawings are intended to provide a further understanding of the invention, and constitutes part of specification, with following tool
Body embodiment is used to explain the present invention together, but is not construed as limiting the invention.In the accompanying drawings:
Fig. 1 is the reaction equation of 2- o-methyl-phenyl benzothiazole and aromatic acid；
Fig. 2 a is the 2-[4-morpholinodithio -3- aminomethyl phenyl benzoic ether of preparation1H NMR。
Fig. 2 b is the 2-[4-morpholinodithio -3- aminomethyl phenyl benzoic ether of preparation13C NMR。
Fig. 3 a is the 2-[4-morpholinodithio -3- aminomethyl phenyl -4- methoxy benzoic acid ester of preparation1H NMR。
Fig. 3 b is the 2-[4-morpholinodithio -3- aminomethyl phenyl -4- methoxy benzoic acid ester of preparation13C NMR。
Fig. 4 a is the 2-[4-morpholinodithio -3- aminomethyl phenyl -4- chlorobenzoic acid ester of preparation1H NMR。
Fig. 4 b is the 2-[4-morpholinodithio -3- aminomethyl phenyl -4- chlorobenzoic acid ester of preparation13C NMR。
Fig. 5 a is 2-[4-morpholinodithio -3- aminomethyl phenyl -2-Thiophene Carboxylic Acid ester of preparation1H NMR。
Fig. 5 b is 2-[4-morpholinodithio -3- aminomethyl phenyl -2-Thiophene Carboxylic Acid ester of preparation13C NMR。
Fig. 6 a is the 2-[4-morpholinodithio -3- aminomethyl phenyl propionic ester of preparation1H NMR。
Fig. 6 b is the 2-[4-morpholinodithio -3- aminomethyl phenyl propionic ester of preparation13C NMR。
Fig. 7 a is the 2-[4-morpholinodithio -4- aminomethyl phenyl benzoic ether of preparation1H NMR。
Fig. 7 b is the 2-[4-morpholinodithio -4- aminomethyl phenyl benzoic ether of preparation13C NMR。
Fig. 8 a is 2- (6 '-methoxybenzothiazole) -3- aminomethyl phenyl benzoic ether of preparation1H NMR。
Fig. 8 b is 2- (6 '-methoxybenzothiazole) -3- aminomethyl phenyl benzoic ether of preparation13C NMR。
Specific embodiment
Detailed description of the preferred embodiments below.It should be understood that described herein specific
Embodiment is merely to illustrate and explain the present invention, and is not intended to restrict the invention.
The endpoint of disclosed range and any value are not limited to the accurate range or value herein, these ranges or
Value should be understood as comprising the value close to these ranges or value.For numberical range, between the endpoint value of each range, respectively
It can be combined with each other between the endpoint value of a range and individual point value, and individually between point value and obtain one or more
New numberical range, these numberical ranges should be considered as specific open herein.
The present invention provides a kind of synthetic methods of benzothiazole ester derivative characterized by comprising in blended sliver
Under part, benzothiazole derivant shown in formula I, organic carboxyl acid, copper catalyst and silver salt are heated to reaction in organic solvent, obtained
To the benzothiazole ester derivative as shown in formula II, X is the ester group in the organic carboxyl acid in formula II；
Wherein, R1For H or 6-OCH3；R2
For 2 '-CH3、3′-CH3、4′-Cl。
Through the above technical solutions, all existing for benzothiazole ester derivative the present invention overcomes synthesizing in the prior art
More defects provide a kind of synthetic method for synthesizing benzothiazole ester derivative, using silver salt as oxidant, cheap copper catalysis
Agent such as (one of copper acetate, copper sulphate, cuprous bromide, cuprous oxide and cuprous iodide or a variety of) is catalyzed benzothiazole and spreads out
Biology reacts in organic solvent with organic carboxyl acid, and benzothiazole ester derivative can be obtained.Compared with prior art, this hair
It is bright to have the advantage that (1) carries out in air atmosphere, it is at low cost；(2) not using noble metals such as palladium, rutheniums, but oxidation is utilized
It is cuprous etc. to make catalyst, save the cost；(3) reaction raw materials are cheap and are easy to get；(4) synthetic method is high-efficient, and use scope is wide,
It is suitble to a variety of substrate reactions.This method carries out in air atmosphere, at low cost, does not have to use highly toxic substrate or organic molten
Agent does not need your catalyst such as precious metal palladium yet, and the raw material in the present invention is easy to get, and synthesis step is simple, and side reaction is few, and target produces
Produce rate is high, and promotional value is high.
In the above-mentioned technical solutions, organic carboxyl acid can there are many selections, on benzothiazole derivant and different carboxylic acids
It states and is reacted under technical solution, the benzothiazole ester derivative that available different ester group replaces.In order to improve target product
Yield, in a kind of preferred embodiment of the present invention, it is preferable that the organic carboxyl acid is thiophene -2-carboxylic acid, propionic acid, 2-
Phenylbutyric acid or the aromatic acid as shown in formula III；
Wherein R3For H, 4-CH3、4-OCH3, 4-Cl, n=0,1.I.e. when n is 0, formula V
Shown in aromatic acid be benzoic acid or the benzoic acid containing substituent group；When n is 1, aromatic acid shown in formula V be cinnamic acid or
Cinnamic acid containing substituent group.
In the above-mentioned technical solutions, the dosage of each raw material can be selected in a wider range, of the invention a kind of preferred
Embodiment in, in order to improve the yield of target product, reduce side reaction, and be conducive to the purifying of subsequent products, it is preferable that formula
The molar ratio of benzothiazole derivant, organic carboxyl acid shown in I, copper catalyst and silver salt is 1:1.5-2.2:0.05-0.2:1-
2。
In the above-mentioned technical solutions, the condition for heating reaction can adjust in a wider range, of the invention a kind of preferred
In embodiment, in order to improve the yield of target product, side reaction is reduced, and be conducive to the purifying of subsequent products, it is preferable that heating
The temperature of reaction is 130 DEG C -140 DEG C.Further, reaction process does not need isolation air, can be in the feelings of ingress of air
It is carried out under condition.
In the above-mentioned technical solutions, the condition for heating reaction can adjust in a wider range, of the invention a kind of preferred
In embodiment, in order to improve the yield of target product, side reaction is reduced, and be conducive to the purifying of subsequent products, it is preferable that reaction
Time is 18-24h.
In the above-mentioned technical solutions, copper catalyst can there are many selections, in a kind of preferred embodiment of the present invention,
In order to improve the yield of target product, side reaction is reduced, it is preferable that copper catalyst is copper acetate, copper sulphate, cuprous bromide, oxygen
Change one of cuprous and cuprous iodide or a variety of.Different copper catalysts is selected, the yield difference for obtaining product is little, exists
Within 10%, in embodiment later, it is illustrated with cuprous oxide.
In the above-mentioned technical solutions, silver salt can there are many selections, in a kind of preferred embodiment of the present invention, in order to
The yield of target product is improved, side reaction is reduced, it is preferable that silver salt is one of silver carbonate, silver acetate and silver oxide or more
Kind.Different silver salt is selected, the yield difference for obtaining product is little, within 10%, in embodiment later, with carbonic acid
Silver is illustrated.
In the above-mentioned technical solutions, organic solvent can there are many selections, in a kind of preferred embodiment of the present invention,
In order to improve the yield of target product, reducing side reaction and be conducive to the purifying of product, it is preferable that the organic solvent is selected from chlorobenzene
With or one of paraxylene or a variety of.In embodiment later, it is illustrated with chlorobenzene.
In the above-mentioned technical solutions, target product further includes in a kind of preferred embodiment of the present invention in order to obtain
The step of mixture obtained after heating reaction is isolated and purified.
For the purification process of target product, it can be carried out by the way of conventional, in order to simplify purification step, and be obtained
The target product of higher yields, in a kind of preferred embodiment of the present invention, described the step of isolating and purifying includes: will be to adding
It is dry with anhydrous sodium sulfate after the mixture obtained after thermal response is extracted with ethyl acetate, it is then concentrated under reduced pressure, obtains crude product；
Using volume ratio as petroleum ether: ethyl acetate=10:1 mixed solvent is that solvent by column chromatography for separation obtains benzothiazole
Ester derivative.
The present invention will be described in detail by way of examples below.
Embodiment 1
The synthesis of 2-[4-morpholinodithio -3- aminomethyl phenyl benzoic ether, comprising the following steps:
A, 0.2mmol o-methyl-phenyl benzothiazole is taken, 0.4mmol benzoic acid is placed in reaction tube, is subsequently successively added
Enter 0.02mmol Cu2O、0.4mmol Ag2CO3, 3mL PhCl, be stirred to react 18h at 140 DEG C.
B, product is extracted with ethyl acetate, anhydrous sodium sulfate is dry, is concentrated under reduced pressure, crude product is obtained, by crude product
White solid is purified to obtain with silica gel column chromatography (solvent volume ratio is petroleum ether: ethyl acetate=10:1).As a result such as Fig. 2 a and figure
Shown in 2b, it was demonstrated that be target product, be computed, yield 83%.
1H NMR(500MHz,CDCl3): δ 8.06 (d, J=8.0Hz, 1H), 7.94 (d, J=7.5Hz, 2H), 7.85 (d, J
=8.0Hz, 1H), 7.52-7.45 (m, 3H), 7.39-7.32 (m, 3H), 7.27 (d, J=7.5Hz, 1H), 7.22 (d, J=
8.0Hz,1H),2.38(s,3H).13C NMR(125MHz,CDCl3):δ165.1,162.8,153.2,149.4,139.8,
136.1,133.6,130.6,130.2,129.1,128.5,128.2,127.0,126.0,125.3,123.5,121.5,
120.1,20.4.HRMS(ESI):Calcd for C21H16NO2S[M+H]+364.0902,found 346.0910.
Individual's guess principle are as follows: first, Cu2O is oxidized, and the active catalyst and 2- phenylbenzothiazol of generation form ring
Metallated intermediate, later by benzoic acid free-radical oxidation at Cu (III) intermediate of high activity, finally, being eliminated by reduction
Journey releases product.Reaction process is as shown in Figure 1.
Embodiment 2
The synthesis of 2-[4-morpholinodithio -3- aminomethyl phenyl -4- methoxy benzoic acid ester, comprising the following steps:
A, 0.2mmol o-methyl-phenyl benzothiazole is taken, 0.4mmol 4- methoxy benzoic acid is placed in reaction tube, then so
After sequentially add 0.02mmol Cu2O、0.4mmol Ag2CO3, 3mL PhCl, be stirred to react 18h at 140 DEG C.
B, product is extracted with ethyl acetate, anhydrous sodium sulfate is dry, is concentrated under reduced pressure, crude product is obtained, by crude product
Colourless liquid is purified to obtain with silica gel column chromatography (solvent volume ratio is petroleum ether: ethyl acetate=10:1).As a result such as Fig. 3 a and figure
Shown in 3b, it was demonstrated that be target product, be computed, yield 73%
1H NMR(500MHz,CDCl3): δ 7.97 (d, J=8.0Hz, 1H), 7.81-7.79 (m, 2H), 7.73 (d, J=
8.0Hz,1H),7.37-7.32(m,2H),7.27-7.24(m,1H),7.15-7.09(m,2H),6.71-6.69(m,2H),
3.67(s,3H),2.27(s,3H).13C NMR(100MHz,CDCl3):δ164.5,163.5,162.6,152.9,149.1,
139.4,135.8,132.0,130.3,127.8,126.7,125.7,124.9,123.2,121.2,121.0,113.4,55.1,
20.1.HRMS(ESI):Calcd for C22H18NO3S[M+H]+376.1007,found 376.1003。
Embodiment 3
The synthesis of 2-[4-morpholinodithio -3- aminomethyl phenyl -4- chlorobenzoic acid ester, comprising the following steps:
A, take 0.2mmol o-methyl-phenyl benzothiazole, 0.4mmol 4- chlorobenzoic acid is placed in reaction tube, subsequently according to
Secondary addition 0.02mmol Cu2O、0.4mmol Ag2CO3, 3mL PhCl, be stirred to react 18h at 140 DEG C.
B, product is extracted with ethyl acetate, anhydrous sodium sulfate is dry, is concentrated under reduced pressure, crude product is obtained, by crude product
Yellow liquid is purified to obtain with silica gel column chromatography (solvent volume ratio is petroleum ether: ethyl acetate=10:1).As a result such as Fig. 4 a and figure
Shown in 4b, it was demonstrated that be target product, be computed, yield 83%
1H NMR(500MHz,CDCl3): δ 7.96 (d, J=8.0Hz, 1H), 7.77-7.74 (m, 3H), 7.39-7.34 (m,
2H), 7.30-7.28 (m, 1H), 7.21-7.16 (m, 3H), 7.12 (d, J=8.5Hz, 1H), 2.28 (s, 3H)13C NMR
(100MHz,CDCl3):δ164.2,162.6,153.2,149.2,140.1,139.9,136.0,131.6,130.7,128.9,
128.4,127.5,127.0,126.2,125.4,123.6,121.6,120.5,20.4.HRMS(ESI):Calcd for
C21H15ClNO2S[M+H]+380.0512,found 380.0507.
Embodiment 4
The synthesis of 2-[4-morpholinodithio -3- aminomethyl phenyl -2-Thiophene Carboxylic Acid ester, comprising the following steps:
A, take 0.2mmol o-methyl-phenyl benzothiazole, 0.4mmol thiophene -2-carboxylic acid is placed in reaction tube, subsequently according to
Secondary addition 0.02mmol Cu2O、0.4mmol Ag2CO3, 3mL PhCl, be stirred to react 18h at 140 DEG C.
B, product is extracted with ethyl acetate, anhydrous sodium sulfate is dry, is concentrated under reduced pressure, crude product is obtained, by crude product
Yellow liquid is purified to obtain with silica gel column chromatography (solvent volume ratio is petroleum ether: ethyl acetate=10:1).As a result such as Fig. 5 a and figure
Shown in 5b, it was demonstrated that be target product, be computed, yield 41%
1H NMR(400MHz,CDCl3): δ 8.10 (d, J=8.0Hz, 1H), 7.90 (d, J=7.6Hz, 1H), 7.77 (dd,
J=3.6,1.2Hz, 1H), 7.54-7.46 (m, 3H), 7.43-7.39 (m, 1H), 7.30-7.28 (m, 2H), 7.03 (dd, J=
5.2,4.0Hz,1H),2.40(s,3H).13C NMR(100MHz,CDCl3):δ162.7,160.4,153.2,148.9,139.9,
136.2,134.9,133.8,132.3,130.7,128.4,128.0,127.0,126.1,125.3,123.6,121.6,
120.5,20.4.HRMS(ESI):Calcd for C19H14NO2S2[M+H]+352.0466,found 352.0467.
Embodiment 5
The synthesis of 2-[4-morpholinodithio -3- aminomethyl phenyl propionic ester, comprising the following steps:
A, 0.2mmol o-methyl-phenyl benzothiazole is taken, 0.4mmol propionic acid is placed in reaction tube, subsequently sequentially adds
0.02mmol Cu2O、0.4mmol Ag2CO3, 3mL PhCl, be stirred to react 18h at 140 DEG C.
B, product is extracted with ethyl acetate, anhydrous sodium sulfate is dry, is concentrated under reduced pressure, crude product is obtained, by crude product
Yellow liquid is purified to obtain with silica gel column chromatography (solvent volume ratio is petroleum ether: ethyl acetate=10:1).As a result such as Fig. 6 a and figure
Shown in 6b, it was demonstrated that be target product, be computed, yield 53%
1H NMR(400MHz,CDCl3): δ 8.13 (d, J=8.0Hz, 1H), 7.94 (d, J=8.0Hz, 1H), 7.55-
7.51 (m, 1H), 7.46-7.39 (m, 2H), 7.06 (d, J=8.0Hz, 1H), 7.22 (d, J=7.6Hz, 1H), 2.36-2.30
(m, 5H), 1.00 (t, J=7.6Hz, 3H)13C NMR(100MHz,CDCl3):δ173.0,163.0,153.4,149.3,
139.7,136.3,130.7,128.2,127.1,126.3,125.5,123.7,121.7,120.6,27.7,20.4,
9.1.HRMS(APCI):Calcd for C17H16NO2S[M+H]+298.0901,found 298.0898.
Embodiment 6
The synthesis of 2-[4-morpholinodithio -4- aminomethyl phenyl benzoic ether, comprising the following steps:
A, take aminomethyl phenyl benzothiazole between 0.2mmol, 0.4mmol benzoic acid is placed in reaction tube, subsequently successively plus
Enter 0.02mmol Cu2O、0.4mmol Ag2CO3, 3mL PhCl, be stirred to react 18h at 140 DEG C.
B, product is extracted with ethyl acetate, anhydrous sodium sulfate is dry, is concentrated under reduced pressure, crude product is obtained, by crude product
White solid is purified to obtain with silica gel column chromatography (solvent volume ratio is petroleum ether: ethyl acetate=10:1).As a result such as Fig. 7 a and figure
Shown in 7b, it was demonstrated that be target product, be computed, yield 45%
1H NMR(400MHz,CDCl3): δ 8.32 (dd, J=8.4,1.2Hz, 2H), 8.23 (s, 1H), 7.95 (d, J=
8.0Hz, 1H), 7.81 (d, J=8.0Hz, 1H), 7.23-7.68 (m, 1H), 7.59-7.55 (m, 2H), 7.47-7.42 (m,
1H), 7.38-7.32 (m, 2H), 7.22 (d, J=8.0Hz, 1H), 2.49 (s, 3H)
13C NMR(100MHz,CDCl3):δ165.5,162.8,152.9,146.7,136.6,135.6,134.0,
132.5,130.9,130.6,129.7,128.9,126.4,126.1,125.4,123.8,123.4,121.6,21.0.HRMS
(APCI):Calcd for C21H16NO2S[M+H]+346.0902,found346.0901.
Embodiment 7
The synthesis of 2- (6 '-methoxybenzothiazole) -3- aminomethyl phenyl benzoic ether, comprising the following steps:
A, 0.2mmol 2- (2- aminomethyl phenyl) -6- methoxybenzothiazole is taken, 0.4mmol benzoic acid is placed in reaction tube
In, subsequently sequentially add 0.02mmol Cu2O、0.4mmol Ag2CO3, 3mL PhCl, be stirred to react 18h at 140 DEG C.
B, product is extracted with ethyl acetate, anhydrous sodium sulfate is dry, is concentrated under reduced pressure, crude product is obtained, by crude product
Colourless liquid is purified to obtain with silica gel column chromatography (solvent volume ratio is petroleum ether: ethyl acetate=10:1).As a result such as Fig. 8 a and figure
Shown in 8b, it was demonstrated that be target product, be computed, yield 88%
1H NMR(400MHz,CDCl3): δ 7.97-7.91 (m, 3H), 7.51 (t, J=7.6Hz, 1H), 7.44 (t, J=
8.0Hz, 1H), 7.35 (t, J=8.0Hz, 2H), 7.28-7.25 (m, 2H), 7.19 (d, J=8.0Hz, 1H), 7.06 (dd, J=
9.2,2.8Hz,1H),3.84(s,3H),2.38(s,3H).13C NMR(100MHz,CDCl3):δ165.3,160.1,157.8,
149.5,147.9,140.0,137.6,133.7,130.6,130.4,129.2,128.6,128.3,127.1,124.1,
120.6,115.7,103.8,55.9,20.6.HRMS(APCI):Calcd for C22H18NO3S[M+H]+376.1007,found
376.1014
The preferred embodiment of the present invention has been described above in detail, still, during present invention is not limited to the embodiments described above
Detail within the scope of the technical concept of the present invention can be with various simple variants of the technical solution of the present invention are made, this
A little simple variants all belong to the scope of protection of the present invention.
It is further to note that specific technical features described in the above specific embodiments, in not lance
In the case where shield, can be combined in any appropriate way, in order to avoid unnecessary repetition, the present invention to it is various can
No further explanation will be given for the combination of energy.
In addition, various embodiments of the present invention can be combined randomly, as long as it is without prejudice to originally
The thought of invention, it should also be regarded as the disclosure of the present invention.
Claims (9)
1. a kind of synthetic method of benzothiazole ester derivative characterized by comprising, will be shown in formula I under mixing condition
Benzothiazole derivant, organic carboxyl acid, copper catalyst and silver salt reaction is heated in organic solvent, obtain as shown in formula II
Benzothiazole ester derivative, X is the ester group in the organic carboxyl acid in formula II；
Wherein, R1For H or 6-OCH3；R2It is 2 '-
CH3、3′-CH3、4′-Cl。
2. synthetic method according to claim 1, wherein the organic carboxyl acid is thiophene -2-carboxylic acid, propionic acid, 2- phenyl
Butyric acid or the aromatic acid as shown in formula III；
Wherein R3For H, 4-CH3、4-OCH3, 4-Cl, n=0,1.
3. synthetic method according to claim 2, wherein benzothiazole derivant shown in formula I, organic carboxyl acid, copper are urged
Agent and the molar ratio of silver salt are 1:1.5-2.2:0.05-0.2:1-2.
4. synthetic method according to claim 2, wherein it is 130 DEG C -140 DEG C that the condition for heating reaction, which includes: temperature,；
And/or reaction time 18-24h.
5. synthetic method according to claim 1-4, wherein copper catalyst is copper acetate, copper sulphate, protobromide
One of copper, cuprous oxide and cuprous iodide are a variety of.
6. synthetic method according to claim 1-4, wherein silver salt is in silver carbonate, silver acetate and silver oxide
It is one or more.
7. synthetic method according to claim 1-4, wherein the organic solvent is selected from chlorobenzene and/or to two
One of toluene is a variety of.
8. synthetic method according to claim 1-4, wherein further include to the mixture obtained after heating reaction
The step of isolating and purifying.
9. synthetic method described in -4 according to claim 1, wherein described the step of isolating and purifying includes:
It is dry with anhydrous sodium sulfate after the mixture obtained after heating reaction is extracted with ethyl acetate, then it is concentrated under reduced pressure,
Obtain crude product；
Using volume ratio as petroleum ether: ethyl acetate=10:1 mixed solvent is that solvent by column chromatography for separation obtains benzo
Thiazole ester derivative.
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Non-Patent Citations (6)
| Title |
|---|
| ASHFAQ AHMAD ET AL.: "Cu（I）-Catalyzed Site Selective Acyloxylation of Indoline Using O2 as the Sole Oxidant", 《ADV. SYNTH. CATAL.》 * |
| CHAO-JUN HU ET AL.: "‘Ligand-free’ palladium-catalyzed direct C–H bond oxidative acyloxylation of 2-arylpyridines with aromatic carboxylic acids", 《TETRAHEDRON LETTERS》 * |
| FEIFAN WANG ET AL.: "Copper-catalyzed C–H acyloxylation of 2-phenylpyridine using oxygen as the oxidant", 《RSC ADVANCES》 * |
| FEIFAN WANG ET AL.: "Copper-Catalyzed Direct Acyloxylation of C(sp2)-H Bonds in Aromatic Amides", 《ORGANIC LETTERS》 * |
| GANG-JIAN LI ET AL.: "Direct Acyloxylation of C(sp2)-H and C(sp2)-X (X = Cl, Br) Bonds in Aromatic Amides Using Copper Bromide and 2-(4,5-Dihydro-oxazol-2-yl)-phenylamine", 《ORGANIC LETTERS》 * |
| SOURAV KUMAR SANTRA ET AL.: "Ceric Ammonium Nitrate (CAN) Promoted PdII-Catalyzed Substrate-Directed o-Benzoxylation and Decarboxylative o-Aroylation", 《EUR. J. ORG. CHEM.》 * |
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