CN106167473B - 1,4,2- dioxy nitrogen azole compounds and its synthetic method - Google Patents
1,4,2- dioxy nitrogen azole compounds and its synthetic method Download PDFInfo
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Abstract
The invention provides one kind 1,4,2- dioxy nitrogen azole compounds and its synthetic method, the method is that reaction raw materials A, B, catalyst are added in organic solvent, is sufficiently reacted at 0~60 DEG C, after reaction decompression removal solvent, 1 that general formula is I is obtained by column chromatographic isolation and purification, 4,2- dioxy nitrogen azole compounds, reaction equation are as follows:
Description
Technical field
The invention belongs to organic compound synthesis field, more particularly, to a kind of Isosorbide-5-Nitrae, 2- dioxy nitrogen azole compounds
And its synthetic method.
Background technique
Isosorbide-5-Nitrae, 2- dioxy nitrogen azoles and its derivative are widely used in chemical field, frequently as mild nitrogen in chemical synthesis
Guest's transfering reagent (Chemical Communications 2016,37,6324-6327), amide reagent (Angewandte
Chemie International Edition 2015,47,14103-14107), moreover it is possible to the protection form as hydroxamic acid
(The Journal of Organic Chemistry 2002,14,4833-4838)；In addition to this, Isosorbide-5-Nitrae, 2- dioxy nitrogen azoles
Bioactivity also with higher and potential physiology, pharmacological activity contain Isosorbide-5-Nitrae, 2- bis- for example, Amir Azam et al. has found
The compound of oxygen nitrogen azoles skeleton has preferable anti-amoeba activity (European Journal of Medicinal
Chemistry 2011,9,4742-4752)。
Reported in document synthesis 1,4,2- dioxy nitrogen azole compounds method mainly include the following types:
Mukaiyama reaction (Bull.Chem.Soc.Jpn.1967,3,664-668) passes through 1, the 3- cycloaddition of nitrile oxide and aldehyde, ketone
Reaction synthesis (Tetrahedron Letters 1967,4,331-334) etc..
As described above, some Isosorbide-5-Nitraes have been disclosed in the prior art, the synthetic method of 2- dioxy nitrogen azole compounds, so
And synthetic method still compares limitation, product is relatively simple.Therefore, for the novel method for synthesizing of such compound, there are still
Continue deeper into necessity and demand of research.
Summary of the invention
In view of this, the invention is directed to a kind of Isosorbide-5-Nitrae, 2- dioxy nitrogen azole compounds and its synthetic method, with
It solves the problems, such as of the existing technology.
In order to achieve the above objectives, the technical solution of the invention is achieved in that
A kind of Isosorbide-5-Nitrae, 2- dioxy nitrogen azole compounds, the general formula of the compound are shown in formula I:
Wherein, carbonyl and Isosorbide-5-Nitrae, be linked as carbon-carbon single bond or phenyl ring between 2- dioxy nitrogen azoles；
R1For at least one of hydrogen, alkyl, nitro or halogen；X is methylene or aryl；
R2For at least one of hydrogen, halogen, alkyl or alkoxy.
Wherein R1, R2Number it is different according to the type of its group connected, such as R1Or R2It can also be and be selected from
A substituent group or more than two identical or different substituent groups in above-mentioned group.
The another object of the invention is to propose the Isosorbide-5-Nitrae, the synthetic method of 2- dioxy nitrogen azole compounds, institute
The method of stating is that reaction raw materials A, B, catalyst are added in organic solvent, sufficiently reacts at 0~60 DEG C, subtracts after reaction
Pressure removal solvent obtains the Isosorbide-5-Nitrae that general formula is I by column chromatographic isolation and purification, and 2- dioxy nitrogen azole compounds, reaction equation is such as
Under:
Wherein, carbonyl and Isosorbide-5-Nitrae in raw material A and product I, be linked as carbon-carbon single bond or phenyl ring between 2- dioxy nitrogen azoles, R is hydrogen
Or chloromethyl, R1For at least one of hydrogen, alkyl, nitro or halogen, Y is bromomethyl or adjacent trimethyl silicon substrate trifluoromethanesulfonic acid
Aromatic ester, X are one of methylene or aryl；R2For at least one of hydrogen, halogen, alkyl or alkoxy, catalyst is fluorine
Salt or villiaumite add alkali.
Further, the catalyst is villiaumite, wherein the villiaumite is tetrabutyl ammonium fluoride and its hydrate.
Further, the catalyst is that villiaumite adds alkali, wherein the alkali is cesium fluoride, cesium carbonate, calcium carbonate, carbonic acid
One or more mixtures of sodium, potassium carbonate and sodium bicarbonate, the villiaumite are tetrabutyl ammonium fluoride and its hydration
Object.
Further, the organic solvent be toluene, methylene chloride, chloroform, Isosorbide-5-Nitrae-dioxane, hexamethylene, just oneself
One or more kinds of mixtures of alkane, bromochloromethane.
Further, the raw material A, raw material B, villiaumite, alkali molar ratio be 1:(1.2~6): (0.6~5): (0~6).
Further, the additional amount of the organic solvent is that 0.25~4mL solvent is added in every 0.25mmol raw material A.
Further, the reaction temperature is 0~60 DEG C, and the reaction time is 10~90 minutes；Preferably, the reaction temperature
Degree is 40 DEG C, and the reaction time is 30 minutes.
Further, it for volume ratio is petroleum ether that the column chromatography for separation step, which uses eluant, eluent: ethyl acetate=(5~
50): 1 mixtures of eluents.
Compared with the existing technology, Isosorbide-5-Nitrae described in the invention, 2- dioxy nitrogen azole compounds and its synthetic method have
Following advantage:
This method is easy to operate, synthetic thread is short out, mild condition, good yields, product are easily separated, in organic synthesis field
And it has a good application prospect in field of medicaments.
Specific embodiment
Unless otherwise stated, term used herein all has the meaning that those skilled in the art routinely understand, in order to
It is easy to understand the present invention, some terms used herein have been subjected to following definitions.
It using in the specification and in the claims, singular type "one" and " this " they include plural reference, unless on
Hereafter separately there is clear statement.For example, term " (one) cell " includes the cell of plural number, including its mixture.
All number marks, such as pH, temperature, time, concentration, including range, are all approximations.It is to be understood that although
Term " about " is all added before always not describing all number marks explicitly.While it will also be understood that, although always not clear
Narration, reagent described herein is only example, and equivalent is known in the art.
It is further illustrated below with reference to specific embodiment, but protection scope of the present invention is not limited to the embodiment expression
Range.
The synthesis of embodiment 1:2- (3-1,4,2- dioxy nitrogen azoles) phenol benzoate (1a)
N-Hydroxyphthalimide (0.25mmol), 2- (trimethyl silicon substrate) phenyl trifluoromethanesulfonate first are added in the reactor
Sulphonic acid ester (0.3mmol), tetrabutyl ammonium fluoride (0.3mmol), methylene chloride (2mL), sealing, are stirred to react 60 points at 60 DEG C
Clock.Be cooled to room temperature, after solvent is removed under reduced pressure, by column chromatographic isolation and purification (eluant, eluent is petroleum ether: ethyl acetate=50:
1) 2- (3-1,4,2- dioxy nitrogen azoles) phenol benzoate (1a) 7.3mg, yield 11% are obtained.
1H NMR(400MHz,Chloroform-d)δ8.12–8.03(m,1H),7.83–7.75(m,1H),7.72–7.62
(m, 2H), 7.44 (t, J=7.8Hz, 2H), 7.29 (t, J=7.4Hz, 1H), 7.24 (t, J=5.9Hz, 2H), 5.85 (s,
2H)；13C NMR(101MHz,CDCl3)δ164.9,159.7,150.7,132.3,131.7,131.2,130.7,130.6,
129.7,126.3,122.8,121.4,99.0；HRMS(ESI):calcd for C15H12NO4 +[M+H]+:270.0761,
found 270.0765.
The synthesis of embodiment 2:2- (3-1,4,2- dioxy nitrogen azoles) phenol benzoate (1a)
N-Hydroxyphthalimide (0.25mmol), 2- (trimethyl silicon substrate) phenyl trifluoromethanesulfonate first are added in the reactor
Sulphonic acid ester (0.3mmol), cesium carbonate (0.9mmol), tetrabutyl ammonium fluoride (0.9mmol), methylene chloride (2mL), sealing, 60
It is stirred to react at DEG C 60 minutes.Put to room temperature, after solvent is removed under reduced pressure, by column chromatographic isolation and purification (eluant, eluent is petroleum ether:
Ethyl acetate=50:1) obtain 2- (3-1,4,2- dioxy nitrogen azoles) phenol benzoate (1a) 14.3mg, yield 21%.
The synthesis of embodiment 3:2- (3-1,4,2- dioxy nitrogen azoles) phenol benzoate (1a)
N- chloromethane epoxide phthalimide (0.25mmol), 2- (trimethyl silicon substrate) phenyl three are added in the reactor
Fluorine methanesulfonates (0.75mmol), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate (0.9mmol), methylene chloride
(6mL), sealing, is stirred to react 90 minutes at 0 DEG C.It is cooled to room temperature, after solvent is removed under reduced pressure, passes through column chromatographic isolation and purification
(eluant, eluent is petroleum ether: ethyl acetate=50:1) obtains 2- (3-1,4,2- dioxy nitrogen azoles) phenol benzoate (1a) 38.0mg,
Yield 57%.
The synthesis of embodiment 4:2- (3-1,4,2- dioxy nitrogen azoles) phenol benzoate (1a)
N- chloromethane epoxide phthalimide (0.25mmol), 2- (trimethyl silicon substrate) phenyl three are added in the reactor
Fluorine methanesulfonates (0.75mmol), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate (0.9mmol), methylene chloride
(2mL), sealing, is stirred to react 30 minutes at 40 DEG C.It is cooled to room temperature, it is pure by column chromatography for separation after solvent is removed under reduced pressure
Change (eluant, eluent is petroleum ether: ethyl acetate=50:1) and obtains 2- (3-1,4,2- dioxy nitrogen azoles) phenol benzoate (1a)
52.0mg, yield 78%.
The synthesis of embodiment 5:2- (3-1,4,2- dioxy nitrogen azoles) phenol benzoate (1a)
N- chloromethane epoxide phthalimide (0.25mmol), 2- (trimethyl silicon substrate) phenyl three are added in the reactor
Fluorine methanesulfonates (0.75mmol), potassium carbonate (1.15mmol), 4-butyl ammonium fluoride trihydrate (0.9mmol), methylene chloride
(2mL), sealing, is stirred to react 30 minutes at 40 DEG C.It is cooled to room temperature, it is pure by column chromatography for separation after solvent is removed under reduced pressure
Change (eluant, eluent is petroleum ether: ethyl acetate=50:1) and obtains 2- (3-1,4,2- dioxy nitrogen azoles) phenol benzoate (1a)
49.1mg, yield 73%.
The synthesis of embodiment 6:2- (3-1,4,2- dioxy nitrogen azoles) Betanaphthyl Benzoate (2a)
N- chloromethane epoxide phthalimide (0.25mmol), trifluoromethanesulfonic acid 3- (trimethyl are added in the reactor
Silicon substrate) -2- naphthalene ester (0.75mmol), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate (0.9mmol), methylene chloride
(2mL), sealing, is stirred to react 30 minutes at 40 DEG C.It is cooled to room temperature, it is pure by column chromatography for separation after solvent is removed under reduced pressure
Change (eluant, eluent is petroleum ether: ethyl acetate=50:1) and obtains 2- (3-1,4,2- dioxy nitrogen azoles) Betanaphthyl Benzoate (2a)
33.4mg, yield 42%.
1H NMR(400MHz,Chloroform-d)δ8.17–8.09(m,1H),7.93–7.79(m,4H),7.74–7.65
(m, 3H), 7.55-7.46 (m, 2H), 7.38 (d, J=8.9Hz, 1H), 5.85 (s, 2H)；13C NMR(101MHz,CDCl3)δ
165.0,159.7,148.4,133.8,132.4,131.7,131.7,131.2,130.7,130.7,129.7,127.8,
127.8,126.7,125.9,122.9,120.7,118.5,99.0；HRMS(ESI):calcd for C19H14NO4 +[M+H]+:
320.0917,found 320.0923.
Embodiment 7:2- (3-1,4,2- dioxy nitrogen azoles) benzoic acid -3,4- dimethoxy-phenyl ester (3a) synthesis
N- chloromethane epoxide phthalimide (0.25mmol), 4,5- dimethoxy -2- (front three are added in the reactor
Base silicon substrate) phenyl trifluoromethanesulfonate methanesulfonates (0.75mmol), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate
(0.9mmol), methylene chloride (2mL), sealing, is stirred to react 30 minutes at 40 DEG C.It is cooled to room temperature, solvent is removed under reduced pressure
Afterwards, 2- (3-1,4,2- dioxy nitrogen azoles) benzene first is obtained by column chromatographic isolation and purification (eluant, eluent is petroleum ether: ethyl acetate=5:1)
Acid -3,4- dimethoxy-phenyl ester (3a) 64.2mg, yield 78%.
1H NMR(400MHz,Chloroform-d)δ8.06(s,1H),7.76(s,1H),7.66(s,2H),6.88(d,J
=8.1Hz, 1H), 6.79 (s, 2H), 5.85 (s, 2H), 3.88 (s, 6H)；13C NMR(101MHz,CDCl3)δ165.3,
159.6,149.5,147.1,144.3,132.3,131.7,131.2,130.6,130.5,122.7,112.7,111.2,
105.4,99.0,56.2,56.0；HRMS(ESI):calcd for C17H16NO6 +[M+H]+:330.0972,found
330.0973.
The synthesis of embodiment 8:2- (3-1,4,2- dioxy nitrogen azoles) benzoic acid -3,4- (methylene-dioxy) phenyl ester (4a)
N- chloromethane epoxide phthalimide (0.25mmol), 4,5- methylene-dioxy -2- (three are added in the reactor
Methylsilyl) phenyl trifluoromethanesulfonate methanesulfonates (0.75mmol), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate
(0.9mmol), methylene chloride (2mL), sealing, is stirred to react 30 minutes at 40 DEG C.It is cooled to room temperature, solvent is removed under reduced pressure
Afterwards, 2- (3-1,4,2- dioxy nitrogen azoles) benzene is obtained by column chromatographic isolation and purification (eluant, eluent is petroleum ether: ethyl acetate=20:1)
Formic acid -3,4- (methylene-dioxy) phenyl ester (4a) 45.6mg, yield 58%.
1H NMR(400MHz,Chloroform-d)δ8.03(s,1H),7.77(s,1H),7.67(s,2H),6.82(d,J
=7.7Hz, 1H), 6.76 (s, 1H), 6.67 (d, J=8.3Hz, 1H), 6.00 (s, 2H), 5.86 (s, 2H)；13C NMR
(101MHz,CDCl3)δ165.3,159.6,148.2,145.7,144.9,132.3,131.7,131.1,130.6,130.5,
122.7,113.8,108.1,103.5,101.9,99.0；HRMS(ESI):calcd for C16H12NO6 +[M+H]+:
314.0659,found 314.0657.
The synthesis of two fluoro- phenyl ester (5a) of embodiment 9:2- (3-1,4,2- dioxy nitrogen azoles) benzoic acid -3,4-
N- chloromethane epoxide phthalimide (0.25mmol), the fluoro- 2- (trimethyl silicane of 4,5- bis- are added in the reactor
Base) phenyl trifluoromethanesulfonate methanesulfonates (0.75mmol), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate (0.9mmol),
Methylene chloride (2mL), sealing, is stirred to react 30 minutes at 40 DEG C.It is cooled to room temperature, after solvent is removed under reduced pressure, passes through column layer
Analysis isolates and purifies (eluant, eluent is petroleum ether: ethyl acetate=20:1) and obtains 2- (3-1,4,2- dioxy nitrogen azoles) benzoic acid -3,4- two
Fluoro- phenyl ester (5a) 33.4mg, yield 44%.
1H NMR(400MHz,Chloroform-d)δ8.05–7.98(m,1H),7.84–7.76(m,1H),7.72–7.64
(m, 2H), 7.22 (d, J=9.8Hz, 1H), 7.19-7.11 (m, 1H), 7.01 (d, J=9.0Hz, 1H), 5.86 (s, 2H)；13C
NMR(101MHz,CDCl3)δ164.7,159.3,151.5,151.4,149.8,149.7,149.0,148.9,147.4,
147.2,146.3,146.2,146.2,146.2,132.5,131.7,130.6,130.5,130.4,122.6,117.6,
117.5,117.5,117.5,117.4,111.7,111.5,99.0；HRMS(ESI):calcd for C15H10F2NO4 +[M+H]+:
306.0572,found 306.0569.
The synthesis of embodiment 10:2- (3-1,4,2- dioxy nitrogen azoles) benzoic acid -2,5- dimethyl-phenyl ester (6a)
N- chloromethane epoxide phthalimide (0.25mmol), 3,6- dimethyl -2- (trimethyl are added in the reactor
Silicon substrate) phenyl trifluoromethanesulfonate methanesulfonates (0.75mmol), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate
(0.9mmol), methylene chloride (2mL), sealing, is stirred to react 30 minutes at 40 DEG C.It is cooled to room temperature, solvent is removed under reduced pressure
Afterwards, 2- (3-1,4,2- dioxy nitrogen azoles) benzene is obtained by column chromatographic isolation and purification (eluant, eluent is petroleum ether: ethyl acetate=20:1)
Formic acid -2,5- dimethyl-phenyl ester (6a) 58.7mg, yield 79%.
1H NMR(400MHz,Chloroform-d)δ8.19–8.12(m,1H),7.81–7.75(m,1H),7.72–7.65
(m, 2H), 7.16 (d, J=7.6Hz, 1H), 7.01 (d, J=10.1Hz, 2H), 5.86 (s, 2H), 2.36 (s, 3H), 2.20 (s,
3H)；13C NMR(101MHz,CDCl3)δ164.4,159.8,149.1,137.2,132.5,131.7,131.1,131.0,
130.9,130.7,127.3,126.9,123.2,122.1,99.0,21.0,15.9；HRMS(ESI):calcd for
C17H16NO4 +[M+H]+:298.1074,found 298.1074.
The synthesis of embodiment 11:2- (3-1,4,2- dioxy nitrogen azoles) -6- nitrobenzoyl acid phenenyl ester (7a)
3- nitro-N- chloromethane epoxide phthalimide (0.25mmol), 2- (trimethyl silicane are added in the reactor
Base) phenyl trifluoromethanesulfonate methanesulfonates (0.75mmol), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate (0.9mmol),
Methylene chloride (2mL), sealing, is stirred to react 30 minutes at 40 DEG C.It is cooled to room temperature, after solvent is removed under reduced pressure, passes through column layer
Analysis isolates and purifies (eluant, eluent is petroleum ether: ethyl acetate=15:1) and obtains 2- (3-1,4,2- dioxy nitrogen azoles) -6- nitrobenzoic acid
Phenyl ester (7a) 9.5mg, yield 12%.
1H NMR (400MHz, Chloroform-d) δ 8.39 (d, J=8.2Hz, 1H), 8.20 (d, J=7.8Hz, 1H),
7.74 (t, J=8.1Hz, 1H), 7.44 (t, J=7.9Hz, 2H), 7.36 (d, J=7.2Hz, 2H), 7.33-7.25 (m, 1H),
5.91(s,2H)；13C NMR(101MHz,CDCl3)δ163.1,156.8,150.4,146.4,134.0,130.9,129.7,
128.5,127.4,126.6,122.4,121.4,99.4；HRMS(ESI):calcd for C15H11N2O6 +[M+H]+:
315.0612,found 315.0613.
The synthesis of the chloro- 6- of embodiment 12:2,3,4,5- tetra- (3-1,4,2- dioxy nitrogen azoles)-phenol benzoate (8a)
The chloro- N- chloromethane epoxide phthalimide (0.25mmol) of 3,4,5,6- tetra-, 2- (front three are added in the reactor
Base silicon substrate) phenyl trifluoromethanesulfonate methanesulfonates (0.75mmol), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate
(0.9mmol), methylene chloride (2mL), sealing, is stirred to react 30 minutes at 40 DEG C.It is cooled to room temperature, solvent is removed under reduced pressure
Afterwards, by column chromatographic isolation and purification (eluant, eluent is petroleum ether: ethyl acetate=50:1) 2,3,4,5- tetra- chloro- 6- (3-1,4,
2- dioxy nitrogen azoles)-phenol benzoate (8a) 23.4mg, yield 27%.
1H NMR (400MHz, Chloroform-d) δ 7.42 (t, J=7.7Hz, 2H), 7.29 (d, J=7.4Hz, 1H),
7.21 (d, J=8.0Hz, 2H), 5.90 (s, 2H)；13C NMR(101MHz,CDCl3)δ161.9,155.8,150.2,137.6,
136.4,134.4,133.6,130.6,129.8,126.8,121.3,121.2,99.7；HRMS(ESI):calcd for
C15H8Cl4NO4 +[M+H]+:405.9202,found 405.9199.
The synthesis of embodiment 13:3- (3-1,4,2- dioxy nitrogen azoles)-phenyl propionate (9a)
N- chloromethane epoxide fourth dicarboximide (0.25mmol), 2- (trimethyl silicon substrate) phenyl trifluoromethanesulfonate are added in the reactor
Methanesulfonates (0.75mmol), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate (0.9mmol), methylene chloride
(2mL), sealing, is stirred to react 30 minutes at 40 DEG C.It is cooled to room temperature, it is pure by column chromatography for separation after solvent is removed under reduced pressure
Change (eluant, eluent is petroleum ether: ethyl acetate=20:1) and obtain 3- (3-1,4,2- dioxy nitrogen azoles)-phenyl propionate (9a) 35.0mg, produces
Rate 63%.
1H NMR (400MHz, Chloroform-d) δ 7.42 (t, J=7.9Hz, 2H), 7.29 (d, J=7.9Hz, 1H),
7.14 (d, J=7.8Hz, 2H), 5.73 (s, 2H), 2.98 (t, J=7.0Hz, 2H), 2.87 (t, J=7.0Hz, 2H)；13C NMR
(101MHz,CDCl3)δ170.1,160.3,150.5,129.5,126.1,121.5,98.2,29.9,19.3；HRMS(ESI):
calcd for C11H12NO4 +[M+H]+:222.0761,found 222.0761.
The synthesis of embodiment 14:2- (3-1,4,2- dioxy nitrogen azoles)-benzoate (10a)
N- chloromethane epoxide phthalimide (0.25mmol) is added in the reactor, (1.5mmol makees bromochloromethane
Reactant B), cesium carbonate (0.9mmol), 4-butyl ammonium fluoride trihydrate (0.9mmol), bromochloromethane (1.9mL makees solvent)
Sealing, is stirred to react 60 minutes at 60 DEG C.It is cooled to room temperature, after solvent is removed under reduced pressure, passes through column chromatographic isolation and purification (elution
Agent is petroleum ether: ethyl acetate=50:1) obtain 2- (3-1,4,2- dioxy nitrogen azoles)-benzoate (10a) 25.1mg, yield
46%.
1H NMR (400MHz, Chloroform-d) δ 7.93 (d, J=6.5Hz, 1H), 7.76 (d, J=7.9Hz, 1H),
7.68-7.60 (m, 2H), 5.91 (d, J=5.1Hz, 4H)；13C NMR(101MHz,CDCl3)13C NMR(101MHz,CDCl3)
δ164.3,159.4,132.6,131.6,130.7,130.5,130.1,122.9,99.0,69.5；HRMS(ESI):calcd
for C10H9ClNO4 +[M+H]+:242.0215,found 242.0220.
The foregoing is merely the preferred embodiments of the invention, are not intended to limit the invention creation, all at this
Within the spirit and principle of innovation and creation, any modification, equivalent replacement, improvement and so on should be included in the invention
Protection scope within.
Claims (8)
1. a kind of Isosorbide-5-Nitrae, the synthetic method of 2- dioxy nitrogen azole compounds, which is characterized in that the general formula of the compound such as Formulas I institute
Show:
Wherein, carbonyl and Isosorbide-5-Nitrae, be linked as carbon-carbon single bond or phenyl ring between 2- dioxy nitrogen azoles；
R1For at least one of hydrogen, alkyl, nitro or halogen；X is methylene or aryl；
R2For at least one of hydrogen, halogen, alkyl or alkoxy；
The synthetic method of the compound is that reaction raw materials A, B, catalyst are added in organic solvent, is filled at 0~60 DEG C
Divide reaction, after reaction decompression removal solvent, the Isosorbide-5-Nitrae that general formula is I, 2- dioxy nitrogen azole are obtained by column chromatographic isolation and purification
Compound, reaction equation are as follows:
Wherein, carbonyl and Isosorbide-5-Nitrae in raw material A and product I, be linked as carbon-carbon single bond or phenyl ring between 2- dioxy nitrogen azoles；R is hydrogen or chlorine
Methyl；R1For at least one of hydrogen, alkyl, nitro or halogen；Y is bromomethyl or adjacent trimethyl silicon substrate trifluoromethanesulfonic acid virtue
Ester；X is one of methylene or aryl；R2For at least one of hydrogen, halogen, alkyl or alkoxy；Catalyst is villiaumite
Or villiaumite adds alkali, wherein the villiaumite is tetrabutyl ammonium fluoride and its hydrate.
2. Isosorbide-5-Nitrae according to claim 1, the synthetic method of 2- dioxy nitrogen azole compounds, it is characterised in that: the catalysis
Agent is that villiaumite adds alkali, wherein the alkali is one in cesium fluoride, cesium carbonate, calcium carbonate, sodium carbonate, potassium carbonate and sodium bicarbonate
Kind or two or more mixtures, the villiaumite are tetrabutyl ammonium fluoride and its hydrate.
3. Isosorbide-5-Nitrae according to claim 1, the synthetic method of 2- dioxy nitrogen azole compounds, it is characterised in that: described has
Solvent be toluene, methylene chloride, chloroform, 1,4- dioxane, hexamethylene, n-hexane, bromochloromethane it is one or two kinds of with
Upper mixture.
4. Isosorbide-5-Nitrae according to claim 1, the synthetic method of 2- dioxy nitrogen azole compounds, it is characterised in that: the raw material
A, raw material B, villiaumite, alkali molar ratio be 1:(1.2~6): (0.6~5): (0~6).
5. Isosorbide-5-Nitrae according to claim 1, the synthetic method of 2- dioxy nitrogen azole compounds, it is characterised in that: described organic
The additional amount of solvent is that 0.25~4mL solvent is added in every 0.25mmol raw material A.
6. Isosorbide-5-Nitrae according to claim 1, the synthetic method of 2- dioxy nitrogen azole compounds, it is characterised in that: the reaction
Temperature is 0~60 DEG C, and the reaction time is 10~90 minutes.
7. Isosorbide-5-Nitrae according to claim 1, the synthetic method of 2- dioxy nitrogen azole compounds, it is characterised in that: the column layer
It for volume ratio is petroleum ether that analysis separating step, which uses eluant, eluent: ethyl acetate=(5~50): 1 mixtures of eluents.
8. Isosorbide-5-Nitrae according to claim 1 or 6, the synthetic method of 2- dioxy nitrogen azole compounds, it is characterised in that: described
Reaction temperature is 40 DEG C, and the reaction time is 30 minutes.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1125931B (en) * | 1960-04-05 | 1962-03-22 | Hoechst Ag | Process for the preparation of 1, 3, 4-dioxazolines |
| US3178426A (en) * | 1962-10-29 | 1965-04-13 | Olin Mathieson | 1, 3, 4-dioxazolyl-cephalosporin derivatives |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1125931B (en) * | 1960-04-05 | 1962-03-22 | Hoechst Ag | Process for the preparation of 1, 3, 4-dioxazolines |
| US3178426A (en) * | 1962-10-29 | 1965-04-13 | Olin Mathieson | 1, 3, 4-dioxazolyl-cephalosporin derivatives |
Non-Patent Citations (2)
| Title |
|---|
| X: Aroylnitrenes for Heterocycle Synthesis.《Synthesis》.2001,(第8期), |
| Y.Roeske等.The Photochemistry of Acyl Azides |
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