CN107417679A - 1,3 azoles substitute the preparation method of pyrazine compounds - Google Patents
1,3 azoles substitute the preparation method of pyrazine compounds Download PDFInfo
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- CN107417679A CN107417679A CN201710659976.3A CN201710659976A CN107417679A CN 107417679 A CN107417679 A CN 107417679A CN 201710659976 A CN201710659976 A CN 201710659976A CN 107417679 A CN107417679 A CN 107417679A
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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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/20—Synthetic spices, flavouring agents or condiments
- A23L27/205—Heterocyclic compounds
- A23L27/2056—Heterocyclic compounds having at least two different hetero atoms, at least one being a nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention belongs to technical field of organic synthesis, specifically discloses a kind of preparation method of 1,3 azoles substitution pyrazine compounds, comprises the following steps：（1）By base catalyst, pyrazine oxynitrides and 1,3 azole compounds, which are added in organic solvent, to be reacted, and is subsequently cooled to room temperature, is obtained reaction solution；（2）By step（1）Gained reaction solution is concentrated, and is isolated and purified, and is produced.The present invention is using the method treated different things alike, using alkali as catalyst, with economical and easily available pyrazine oxynitrides and 1,3 azole compounds are raw material, coupling reaction directly occurs in atmosphere and generates corresponding Pyrazine biaryl compound, the azole of product 1,3 substitution pyrazine compounds can be used as antiseptic and insecticide pharmaceutical intermediate, especially fragrance precursors.The synthetic system scope of application of the present invention is wider, and the functional group such as compatible alkyl, technique is simple, easy to operate, and reaction condition is gentle, and substrate spectrum is wider, has higher yield, is adapted to popularization and application.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to 1,3- of one kind azoles substitute the preparation of pyrazine compounds
Method.
Background technology
1,3- azole substitution pyrazine compounds are the more extensive organic synthesis intermediates of a kind of purposes, and also known as heterocycle joins
Aromatic compound, it has important application value in medical production, organic synthesis, electrochemical material.It is existing in the prior art
Synthetic method successfully prepares such pyrazine compound, as palladium chtalyst occurs for 2- tributylstamlyls thiophene and 2- chloropyrazines
Stille coupling reactions, the reaction of benzothiazole and iodo pyrazine etc..However, these synthetic methods still suffer from problems,
Such as react that used catalyst is sufficiently expensive, reaction substrate toxicity is very big and expensive, severe reaction conditions, be not met by industry
The requirement of production.
The content of the invention
In view of the above-mentioned problems, the present invention provides the preparation method of 1,3- of one kind azoles substitution pyrazine compounds, to solve
Existing synthetic method can not meet the problem of demand of industrial production.
To achieve the above object, the technical solution adopted in the present invention is：
1,3- of one kind azoles substitute the preparation method of pyrazine compounds, comprise the following steps：
（1）Base catalyst, pyrazine oxynitrides and 1,3- azole compounds are added in organic solvent and reacted, Ran Houleng
But to room temperature, reaction solution is obtained；
（2）By step（1）Gained reaction solution is concentrated, and is isolated and purified, and is produced.
Preferably, the base catalyst, pyrazine oxynitrides, the mol ratio of 1,3- azole compounds are（2.5~5）:
1:（2~5）.
Preferably, the base catalyst is tert-butyl alcohol lithium, sodium tert-butoxide, potassium tert-butoxide, lithium hydroxide, sodium hydroxide, hydrogen
At least one of potassium oxide, lithium methoxide, sodium methoxide, caustic alcohol, potassium carbonate and triethylamine.
Preferably, the pyrazine oxynitrides is 2,5- dimethyl pyrazines oxynitrides, 2,3- dimethyl pyrazine nitrogen
At least one of oxygen compound, 2,3- diethyl pyrazines oxynitrides and quinoxaline nitrogen oxides.
Preferably, 1, the 3- azole compounds include thiazole, 4- methylthiazols, 4,5- dimethylthiazoles, benzothiazole,
At least one of oxazole, benzoxazoles and 5- methyl benzothiazoles.
Preferably, the organic solvent be toluene, dimethylbenzene, mesitylene, acetonitrile, Isosorbide-5-Nitrae-dioxane, N, N- diformazans
Base formamide, 1,2- dichloroethanes, chlorobenzene, dimethyl sulfoxide (DMSO), N, in accelerine and DMAC N,N' dimethyl acetamide extremely
Few one kind.
Preferably, the dosage of the organic solvent is：Every mole of pyrazine oxynitrides 2~5L organic solvent.
Preferably, step（1）In reaction temperature be 100~160 DEG C, the reaction time is 12~48h.
Preferably, step（2）Described in isolate and purify and concretely comprise the following steps：Caused concentrate is with second after reaction solution is concentrated
Acetoacetic ester/petroleum ether volume ratio 1/（1~3）Or dichloromethane/petroleum ether volume ratio 20/1 is solvent, thin-layer chromatography is carried out
Separation.
The preparation method of 1, the 3- azoles substitution pyrazine compounds of the present invention, reaction principle are as follows（Substituted with 2,5- bis-
Exemplified by pyrazine oxynitrides）：
。
The present invention has following positive beneficial effect：
（1）The present invention is using the method treated different things alike, using alkali as catalyst, with economical and easily available pyrazine oxynitrides and 1,3- azoles
Class compound is raw material, and coupling reaction directly occurs in atmosphere and generates corresponding Pyrazine biaryl compound, product 1,3- azoles
Class substitution pyrazine compounds can be used as antiseptic and insecticide pharmaceutical intermediate, fragrance precursors.
（2）The synthetic system scope of application of the present invention is wider, the functional group such as compatible alkyl.
（3）Preparation method technique of the present invention is simple, and easy to operate, reaction condition is gentle, and substrate spectrum is wider, has higher
Yield, be adapted to popularization and application.
Brief description of the drawings
Fig. 1 is 2,5- dimethyl -3-（2- thiazolyls）The thermal cracking analysis chart of pyrazine.
Embodiment
With reference to specific embodiment, the present invention is described further, but protection scope of the present invention is not limited to
This.
The synthesis of pyrazine oxynitrides：In dry round-bottomed flask, 10mmol pyrazine compounds and 10mL second are added
Solution is made in acid, then adds 1.4mL hydrogenperoxide steam generators（30%）, stirred 72 hours under the conditions of 70 DEG C.Vacuum condition moves down
Except solvent, pH value is adjusted to 9 by remaining mixture with sodium carbonate liquor, uses dichloromethane（3×20mL）Extraction is three times.Merge organic
Solvent is removed under phase, anhydrous sodium sulfate drying, filtering, vacuum condition.Residue pillar layer separation（Silica gel, ethyl acetate first
Alcohol 8:1）.Product passes through1H NMR and high resolution mass spectrum confirm.
。
Embodiment 1
2,5- dimethyl -3-（2- thiazolyls）The preparation method of pyrazine, comprises the following steps：
（1）2,5- dimethyl pyrazine oxynitrides 0.6mmol, thiazole 1.2mmol, tert-butyl alcohol lithium 1.5mmol are taken, adds 2mL
Dimethylbenzene in mixture is made, the mixture is placed in 5mL Schlenk pipes, is placed in 160 DEG C of oil bath and heats, instead
After answering 24h, room temperature is cooled to, obtains reaction solution；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with ethyl acetate/petroleum ether=1/3
(v/v) it is solvent, carries out TLC separation, obtain 53mg target products.
The target product yield of the present embodiment is 46%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 8.35 (s,
1H), 7.98 (d, J = 3.24 Hz, 1H), 7.47 (d, J = 3.20 Hz, 1H), 3.01 (s, 3H), 2.58
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 169.2, 150.1, 148.2, 144.2, 143.7, 143.3,
121.9, 23.5, 21.0。
The gained target product of embodiment 1 is entered using simultaneous thermal analysis instrument (F3 of NETZSCH STA 449, Germany)
Row thermal stability analysis, and be compared by TG-DTG and dsc analysis method.The experiment is run under a nitrogen atmosphere, and flow velocity is
60 mL·min-1, the sample size often run once is 5mg.The temperature range of thermal cracking is 30~900 DEG C, with 10 DEG C of min-1
Constant rate heating.TG curves and DTG curves are obtained simultaneously, sees Fig. 1.The chemical combination can be seen that by thermal cracking analysis chart
Within the temperature range of the mass loss of thing occurs mainly in 112~270 DEG C, mass loss rate reaches 94.9%.When temperature rises to
At 237 DEG C, mass loss rate reaches peak value：25%·min-1.THERMAL STABILITY shows：The compound has fine in room temperature
Stability and it is most of under the high temperature conditions can be cracked into perfume monomer, therefore the compound can be used as hot-working bar
Food flavor under part.
Embodiment 2
2,5- dimethyl -3-（4- methyl -2- thiazolyls）The preparation method of pyrazine, comprises the following steps：
（1）2,5- dimethyl pyrazine oxynitrides 0.6mmol, 4- methylthiazols 1.2mmol, tert-butyl alcohol lithium 1.5mmol are taken, is added
Enter in 2mL dimethylbenzene and mixture is made, the mixture is placed in 5mL Schlenk pipes, be placed in and be heated to 160 DEG C of oil
In bath, after reacting 48h, room temperature is cooled to, obtains reaction solution；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with ethyl acetate/petroleum ether=1/3
(v/v) it is solvent, carries out TLC separation, obtain 48mg target products.
The target product yield of the present embodiment is 39%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 8.32 (s,
1H), 7.01 (s, 1H), 3.00 (s, 3H), 2.57 (s, 3H), 2.54 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 168.0, 154.4, 150.1, 148.2, 143.9, 143.0, 116.6, 23.5, 21.0, 17.5。
Embodiment 3
2,5- dimethyl -3-（4,5- dimethyl -2- thiazolyls）The preparation method of pyrazine, comprises the following steps：
（1）Take 2,5-dimethyl pyrazine oxynitrides 0.6mmol, 4,5- dimethylthiazole 1.2mmol, tert-butyl alcohol lithium
1.5mmol, add in 2mL dimethylbenzene and mixture is made, the mixture is placed in 5mL Schlenk pipes, is placed in and is heated to
In 160 DEG C of oil bath, after reacting 48h, room temperature is cooled to, obtains reaction solution；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with ethyl acetate/petroleum ether=1/3
(v/v) it is solvent, carries out TLC separation, obtain 40mg target products.
The target product yield of the present embodiment is 30%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 8.28 (s,
1H), 2.96 (s, 3H), 2.55 (s, 3H), 2.41 (s, 3H), 2.41 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 163.7, 150.1, 149.9, 147.9, 144.1, 142.5, 129.9, 23.4, 21.0, 15.1,
11.5。
Embodiment 4
2-（3,6- dimethyl -2- pyrazinyls）The preparation method of benzo [d] thiazole, comprises the following steps：
（1）2,5- dimethyl pyrazine oxynitrides 0.6mmol, benzothiazole 1.2mmol, tert-butyl alcohol lithium 1.5mmol are taken, is added
Mixture is made in 2mL dimethylbenzene, the mixture is placed in 5mL Schlenk pipes, is placed in and is heated to 160 DEG C of oil bath
In, after reacting 48h, room temperature is cooled to, obtains reaction solution；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with dichloromethane/petroleum ether=20/1
(v/v) it is solvent, carries out TLC separation, obtain 97mg target products.
The target product yield of the present embodiment is 67%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 8.40 (s,
1H),8.12 (d, J = 8.00 Hz, 1H),7.96 - 7.94 (m, 1H), 7.53 - 7.49 (m, 1H), 7.45
- 7.41 (m, 1H), 3.13 (s, 3H), 2.62 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 169.2,
154.7, 150.4, 149.5, 143.9, 143.7, 136.0, 126.1, 125.8, 124.1, 121.6, 23.7,
21.0。
Embodiment 5
2,5- dimethyl -3-（2- oxazolyls）The preparation method of pyrazine, comprises the following steps：
（1）2,5- dimethyl pyrazine oxynitrides 0.6mmol, oxazole 1.2mmol, tert-butyl alcohol lithium 1.5mmol are taken, adds 2mL
Dimethylbenzene in mixture is made, the mixture is placed in 5mL Schlenk pipes, is placed in and is heated in 160 DEG C of oil bath,
After reacting 48h, room temperature is cooled to, obtains reaction solution；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with ethyl acetate/petroleum ether=1/2
(v/v) it is solvent, carries out TLC separation, obtain 36mg target products.
The target product yield of the present embodiment is 34%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 8.43 (s,
1H), 7.87 (d, J = 0.40 Hz, 1H), 7.38 (d, J = 0.40 Hz, 1H), 2.96 (s, 3H), 2.65
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 159.5, 150.6, 150.2, 144.0, 139.9,
139.2, 128.8, 23.3, 21.2。
Embodiment 6
2-（3,6- dimethyl -2- pyrazinyls）The preparation method of benzo [d] oxazole, comprises the following steps：
（1）2,5- dimethyl pyrazine oxynitrides 0.6mmol, benzoxazoles 1.2mmol, tert-butyl alcohol lithium 1.5mmol are taken, is added
Mixture is made in 2mL dimethylbenzene, the mixture is placed in 5mL Schlenk pipes, is placed in and is heated to 160 DEG C of oil bath
In, after reacting 48h, room temperature is cooled to, obtains reaction solution；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with ethyl acetate/petroleum ether=1/3
(v/v) it is solvent, carries out TLC separation, obtain 58mg target products.
The target product yield of the present embodiment is 43%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 8.50 (s,
1H),7.89 - 7.87 (m, 1H), 7.72 - 7.70 (m, 1H), 7.47 - 7.39 (m, 2H), 3.08 (s,
3H), 2.70 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.3, 151.6, 151.0, 150.6,
144.7, 141.7, 139.3, 126.3, 124.9, 120.9, 111.3, 23.7, 21.3。
Embodiment 7
2-（3,6- dimethyl -2- pyrazinyls）The preparation method of -5- methyl benzo [d] oxazole, comprises the following steps：
（1）2,5- dimethyl pyrazine oxynitrides 0.6mmol, 5- methyl benzothiazoles 1.2mmol, tert-butyl alcohol lithium 1.5mmol are taken,
Add in 2mL dimethylbenzene and mixture is made, the mixture is placed in 5mL Schlenk pipes, is placed in and is heated to 160 DEG C
In oil bath, after reacting 48h, room temperature is cooled to, obtains reaction solution；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with ethyl acetate/petroleum ether=1/3
(v/v) it is solvent, carries out TLC separation, obtain 57mg target products.
The target product yield of the present embodiment is 40%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 8.48 (s,
1H),7.66 (s, 1H),7.57 (d, J = 8.36 Hz, 1H), 7.24 (dd, J = 8.36, 1.04 Hz, 1H),
3.06 (s, 3H), 2.69 (s, 3H), 2.51 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.4,
151.5, 150.9, 148.9, 144.6, 142.0, 139.4, 134.8, 127.5, 120.7, 110.6, 23.7,
21.5, 21.3。
Embodiment 8
2,3- dimethyl -5-（2- thiazolyls）The preparation method of pyrazine, comprises the following steps：
（1）2,3- dimethyl pyrazine oxynitrides 0.6mmol, thiazole 1.2mmol, tert-butyl alcohol lithium 1.5mmol are taken, adds 2mL
Dimethylbenzene in mixture is made, the mixture is placed in 5mL Schlenk pipes, is placed in and is heated in 160 DEG C of oil bath,
After reacting 48h, room temperature is cooled to, obtains reaction solution；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with ethyl acetate/petroleum ether=1/1
(v/v) it is solvent, carries out TLC separation, obtain 30mg target products.
The target product yield of the present embodiment is 26%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 9.12 (s,
1H), 7.94 (d, J = 2.88 Hz, 1H), 7.46 (d, J = 2.92 Hz, 1H), 2.60 (s, 3H), 2.60
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 167.2, 153.3, 152.0, 144.3, 143.7, 137.5,
121.3, 22.1, 22.0。
Embodiment 9
2,3- diethyl -5-（2- thiazolyls）The preparation method of pyrazine, comprises the following steps：
（1）2,3- diethyl pyrazine oxynitrides 0.6mmol, thiazole 1.2mmol, tert-butyl alcohol lithium 1.5mmol are taken, adds 2mL
Dimethylbenzene in mixture is made, the mixture is placed in 5mL Schlenk pipes, is placed in and is heated in 160 DEG C of oil bath,
After reacting 48h, room temperature is cooled to, obtains reaction solution；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with ethyl acetate/petroleum ether=1/2
(v/v) it is solvent, carries out TLC separation, obtain 38mg target products.
The target product yield of the present embodiment is 29%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 9.15 (s,
1H), 7.94 (d, J = 3.20 Hz, 1H), 7.45 (d, J = 3.20 Hz, 1H), 2.91 (q, J = 7.52
Hz, 4H), 1.38 (t, J = 7.48 Hz, 3H), 1.34 (t, J = 7.64 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ 167.7, 157.2, 155.5, 144.2, 143.5, 137.3, 121.3, 27.6, 27.2,
12.8, 12.3。
Embodiment 10
2-（2- thiazolyls）The preparation method of quinoxaline, comprises the following steps：
（1）Quinoxaline nitrogen oxygen 0.6mmol, thiazole 1.2mmol, tert-butyl alcohol lithium 1.5mmol are taken, adds in 2mL dimethylbenzene and is made
Mixture, the mixture is placed in 5mL Schlenk pipes, is placed in and is heated in 160 DEG C of oil bath, after reacting 48h, cooling
To room temperature, reaction solution is obtained；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with ethyl acetate/petroleum ether=1/2
(v/v) it is solvent, carries out TLC separation, obtain 46mg target products.
The target product yield of the present embodiment is 36%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 9.75 (s,
1H), 8.17 - 8.13 (m, 2H), 8.06 (d, J = 3.16 Hz, 1H), 7.83 - 7.78 (m, 2H),
7.59 (d, J = 3.12 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 167.1, 145.9, 144.7,
142.9, 142.6, 141.8, 130.7, 130.5, 129.4, 129.4, 122.8。
Embodiment 11
2-（4- methyl -2- thiazolyls）The preparation method of quinoxaline, comprises the following steps：
（1）Quinoxaline nitrogen oxygen 0.6mmol, 4- methylthiazol 1.2mmol, tert-butyl alcohol lithium 1.5mmol are taken, adds 2mL dimethylbenzene
In mixture is made, the mixture is placed in 5mL Schlenk pipes, is placed in and is heated in 160 DEG C of oil bath, react 48h
Afterwards, room temperature is cooled to, obtains reaction solution；
（2）By step（1）Gained reaction solution directly carries out being concentrated to give concentrate, by concentrate with dichloromethane/petroleum ether=20/1
(v/v) it is solvent, carries out TLC separation, obtain 42mg target products.
The target product yield of the present embodiment is 31%.
Nuclear-magnetism sign is carried out to target product, it is as follows：1H NMR (400 MHz, CDCl3) ppm: δ 9.71 (s,
1H), 8.15 - 8.12 (m, 2H), 7.80 - 7.77 (m, 2H), 7.13 (s, 1H), 2.60 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 166.0, 155.1, 145.9, 142.8, 142.6, 141.8, 130.6,
130.3, 129.4, 129.4, 117.6, 17.3。
The present invention is described in detail above in conjunction with embodiment, still, person of ordinary skill in the field can
Understand, on the premise of present inventive concept is not departed from, each design parameter in above-described embodiment can also be changed, shape
Into multiple specific embodiments, it is common excursion of the invention, is no longer described in detail one by one herein.
Claims (10)
1. one kind 1,3- azoles substitute the preparation method of pyrazine compounds, it is characterised in that comprise the following steps：
（1）Base catalyst, pyrazine oxynitrides and 1,3- azole compounds are added in organic solvent and reacted, Ran Houleng
But to room temperature, reaction solution is obtained；
（2）By step（1）Gained reaction solution is concentrated, and is isolated and purified, and produces 1,3- azoles substitution pyrazine compounds.
2. the preparation method of 1,3- azoles substitution pyrazine compounds according to claim 1, it is characterised in that：The alkali is urged
Agent, pyrazine oxynitrides, the mol ratio of 1,3- azole compounds are（2.5~5）:1:（2~5）.
3. the preparation method of 1,3- azoles substitution pyrazine compounds according to claim 1, it is characterised in that：The alkali is urged
Agent is tert-butyl alcohol lithium, sodium tert-butoxide, potassium tert-butoxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium methoxide, sodium methoxide, second
At least one of sodium alkoxide, potassium carbonate and triethylamine.
4. the preparation method of 1,3- azoles substitution pyrazine compounds according to claim 1, it is characterised in that：The pyrazine
Oxynitrides is 2,5-dimethyl pyrazine oxynitrides, 2,3- dimethyl pyrazines oxynitrides, 2,3- diethyl pyrazines
At least one of oxynitrides and quinoxaline nitrogen oxides.
5. the preparation method of 1,3- azoles substitution pyrazine compounds according to claim 1, it is characterised in that：The 1,3-
Azole compounds include thiazole, 4- methylthiazols, 4,5- dimethylthiazoles, benzothiazole, oxazole, benzoxazoles and 5- methylbenzenes
And at least one of azoles.
6. the preparation method of 1,3- azoles substitution pyrazine compounds according to claim 1, it is characterised in that：It is described organic
Solvent is toluene, dimethylbenzene, mesitylene, acetonitrile, 1,4- dioxane, N,N-dimethylformamide, 1,2- dichloroethanes, chlorine
Benzene, dimethyl sulfoxide (DMSO), N, at least one of accelerine and DMAC N,N' dimethyl acetamide.
7. the preparation method of 1,3- azoles substitution pyrazine compounds according to claim 1, it is characterised in that：It is described organic
The dosage of solvent is：Every mole of pyrazine oxynitrides 2~5L organic solvent；Step（1）In reaction temperature for 100~
160 DEG C, the reaction time is 12~48h.
8. the preparation method of 1,3- azoles substitution pyrazine compounds according to claim 1, it is characterised in that：Step（2）
Described in isolate and purify and concretely comprise the following steps：Caused concentrate is with ethyl acetate/petroleum ether volume ratio 1/ after reaction solution is concentrated
（1~3）Or dichloromethane/petroleum ether volume ratio 20/1 is solvent, TLC separation is carried out.
9. one kind 1,3- azoles substitution pyrazine compounds, are prepared by any one of claim 1~9.
10. application of the 1,3- azoles substitution pyrazine compounds in thermally processed foods fragrance precursor described in claim 9.
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| CN110372613A (en) * | 2019-08-21 | 2019-10-25 | 江南大学 | A kind of 2,3,6- tri- replaces the high efficiency preparation method of pyrazine nitrogen oxygen class compound |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110372613A (en) * | 2019-08-21 | 2019-10-25 | 江南大学 | A kind of 2,3,6- tri- replaces the high efficiency preparation method of pyrazine nitrogen oxygen class compound |
| CN110372613B (en) * | 2019-08-21 | 2020-09-04 | 江南大学 | Preparation method of 2,3, 6-trisubstituted pyrazine nitroxide compound |
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