CN106699777B - A kind of heterocycle compound and synthetic method - Google Patents
A kind of heterocycle compound and synthetic method Download PDFInfo
- Publication number
- CN106699777B CN106699777B CN201611109042.4A CN201611109042A CN106699777B CN 106699777 B CN106699777 B CN 106699777B CN 201611109042 A CN201611109042 A CN 201611109042A CN 106699777 B CN106699777 B CN 106699777B
- Authority
- CN
- China
- Prior art keywords
- compound
- added
- reaction
- triethylamine
- tetrahydrofuran
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Abstract
The invention belongs to field of chemical technology, especially a kind of novel heterocyclic compounds, the chemical structural formula of the heterocyclic compound are as follows:Wherein, substituent R1And R2It is not fixed for hydrogen or alkyl or nitro or halogen or aldehyde radical, substituting group position, number.Synthetic method is with benzothiazole analog derivative, bromination nitrile and alkali one-step method, without catalyst, obtained a kind of novel heterocyclic compounds compound, key point is one-step method, the new synthetic method without catalyst and mild reaction conditions, again because of its heterocycle structure, be conducive to active application in vivo.
Description
Technical field
The present invention relates to field of chemical technology, especially a kind of new heterocycle compound synthetic method.
Background technique
Heterocyclic compound has wide spectrum biological activity, is commonly applied to medicine, many field of fine chemical such as pesticide.In order to
Better bioactive molecule is obtained, constructing new heterocycle is the key that the development of the fine chemical technologies such as medicine, pesticide and core.
In view of the good bioactivity of heterocyclic compound, synthesizes new heterocycle and be of great significance and scientific value.
Summary of the invention
The main purpose of the present invention is to provide the heterocycle compound synthetic methods of a kind of nitrogenous, oxygen and sulphur.
Technical scheme is as follows:
The nitrogenous, oxygen of one kind and thia cyclics, the heterocyclic compound chemical structural formula are as follows:
Wherein, substituent R1And R2For substituent R1And R2For hydrogen or alkyl or nitro or halogen or aldehyde radical, substituent group position
It sets, number is not fixed.
Synthesis nitrogenous, oxygen and thia cyclics the method, the method includes following synthesis paths:
It the described method comprises the following steps:
1) bromination nitrile compound 1, organic solvent is added into reaction flask at room temperature, alkali is cooled to 0 DEG C；
The compound 1 is benzothiazole derivant；
2) it in organic solvent by the dissolution of compound 1, is slowly added into the step 1) mixture, then heats to
25-50 DEG C of reaction.Obtained solid compound purifies to obtain yellow solid compound 2；
Complete the synthesis of new heterocycle compound.
The feed ratio of the step 1) compound 1 and bromination nitrile is 1:1-100.Change feed ratio, the yield of compound 2 has
Large increase.
Step 1) the alkali is triethylamine.If other alkali, reaction does not occur or yield is very low.
Step 1) the solvent is tetrahydrofuran.If other solvents, reaction does not occur or yield is very low.
The sequence that the step 1) feeds intake is bromination nitrile, alkali and compound 1.If other charging sequences can make reaction not
Occur or yield is very low.
Step 1) the reaction condition is to be warming up to 25-50 DEG C, is flowed back 0.5-12 hours.Reach temperature, reaction could be suitable
Benefit carries out, and otherwise reacts insufficient, yield is low, and the reaction time is long.
The feed ratio of the step 1) compound 1 and alkali is 1:1-100.Change feed ratio, the yield of compound 2 has very big
It improves, the range of feed ratio is also larger, is conducive to the production of fine chemicals.
Reaction mechanism is positively charged CN in the present invention+, 1 hydroxyl oxygen atom of attack compound generates intermediate A, and water can be into
Cyano group is attacked, addition reaction occurs and obtains compound B, the sulphur atom intramolecular attack N of electron rich is former on compound B thiazole ring
Son forms intermediate C, and C-S breaks to form compound D, and the another secondary response of water generates compound E, in moving by intramolecular bond
It moves, dehydration generates compound 2.
The present invention has the beneficial effect that:
1, the present invention is reacted with benzothiazole derivant with bromination nitrile, obtains new heterocycle compound 2；
2, the present invention synthesizes a kind of novel nitrogen-containing, oxygen and thia cyclics, provides a kind of no catalyst, one-step method
Simple new synthetic method.
3, the present invention has synthesized a kind of novel nitrogen-containing, oxygen and thia cyclics, and such compound resists insane antitumor
Epilepsy, it is antiviral, there are wide research and application in the fields such as antibacterial.
Specific embodiment
The present invention is further illustrated below with reference to embodiment, but the scope of protection of present invention is not limited to implement
The range of example statement.
Embodiment one
BrCN (157.5mg, 1.5mmol) is added into reaction flask, under nitrogen protection, 1ml tetrahydro furan is added at 0 DEG C
It mutters.It is added in reaction flask after compound 1a (120.5mg, 0.5mmol) is dissolved in 2mL tetrahydrofuran and the mixing of 0.5mL triethylamine,
1h is reacted at 25 DEG C.Reaction system, which chromatographs (eluant, eluent is methylene chloride: petroleum ether=1:1) by simple column, can be obtained mesh
It marks product 20.7mg (0.074mmol).Yellow solid 2a, yield 14.8%.
Embodiment two
BrCN (157.5mg, 1.5mmol) is added into reaction flask, under nitrogen protection, 1ml tetrahydro furan is added at 0 DEG C
It mutters.It is added in reaction flask after compound 1b (113.5mg, 0.5mmol) is dissolved in 2ml tetrahydrofuran and the mixing of 0.5mL triethylamine,
25 DEG C of reaction 1h.Reaction system chromatographed by simple column (eluant, eluent is methylene chloride: petroleum ether: ethyl acetate=20:15:
2) target product 38.5mg (0.14mmol) can be obtained.Yellow solid 2b, yield 28.8%.
Embodiment three
BrCN (157.5mg, 1.5mmol) is added into reaction flask, under nitrogen protection, 1ml tetrahydro furan is added at 0 DEG C
It mutters.It is added in reaction flask after compound 1c (130.5mg, 0.5mmol) is dissolved in 2ml tetrahydrofuran and the mixing of 0.5mL triethylamine,
1h is reacted at 25 DEG C.Reaction system, which chromatographs (eluant, eluent is methylene chloride: petroleum ether=1:3) by simple column, can be obtained mesh
It marks product 108.7mg (0.36mmol).Yellow solid 2c, yield 72%.
Example IV
BrCN (157.5mg, 1.5mmol) is added into reaction flask, under nitrogen protection, 1ml tetrahydro furan is added at 0 DEG C
It mutters.Reaction flask is added after compound 1d (152.5mg, 0.5mmol) is dissolved in 2ml tetrahydrofuran and the mixing of 0.5mL drop triethylamine
In, 1h is reacted under room temperature.Reaction system chromatographs (eluant, eluent is methylene chloride: petroleum ether=1:6) by simple column and can obtain
To target product 92.2mg (0.27mmol).Yellow solid 2d, yield 53.3%.
Embodiment five
BrCN (157.5mg, 1.5mmol) is added into reaction flask, under nitrogen protection, 1ml tetrahydro furan is added at 0 DEG C
It mutters.It is added in reaction flask after compound 1e (136mg, 0.5mmol) is dissolved in 2ml tetrahydrofuran and the mixing of 0.5mL triethylamine, often
Temperature is lower to react 1h.Reaction system, which chromatographs (eluant, eluent is methylene chloride: petroleum ether=1:6) by simple column, can be obtained target
Product 43.5mg (0.14mmol).Yellow solid 2e, yield 27.8%.
Embodiment six
BrCN (157.5mg, 1.5mmol) is added into reaction flask, under nitrogen protection, 1ml tetrahydro furan is added at 0 DEG C
It mutters.It is added in reaction flask after compound 1f (127.5mg, 0.5mmol) is dissolved in 2ml tetrahydrofuran and the mixing of 0.5mL triethylamine,
1h is reacted under room temperature.Reaction system chromatographs (eluant, eluent is ethyl acetate: petroleum ether=1:10) by simple column and can be obtained
Target product 15.5mg (0.053mmol).Yellow solid 2f, yield 10.6%.
Embodiment seven
BrCN (157.5mg, 1.5mmol) is added into reaction flask, under nitrogen protection, 1ml tetrahydro furan is added at 0 DEG C
It mutters.It is added in reaction flask after compound 1g (120.5mg, 0.5mmol) is dissolved in 2ml tetrahydrofuran and the mixing of 0.5mL triethylamine,
1h is reacted under room temperature.Reaction system, which chromatographs (eluant, eluent is methylene chloride: petroleum ether=1:6) by simple column, can be obtained mesh
It marks product 15.2mg (0.054mmol).Yellow solid 2g, yield 10.8%.
Embodiment eight
BrCN (157.5mg, 1.5mmol) is added into reaction flask, under nitrogen protection, 1ml tetrahydro furan is added at 0 DEG C
It mutters.It is added in reaction flask after compound 1h (130.5mg, 0.5mmol) is dissolved in 2ml tetrahydrofuran and the mixing of 0.5mL triethylamine,
1h is reacted under room temperature.Reaction system, which chromatographs (eluant, eluent is methylene chloride: petroleum ether=1:8) by simple column, can be obtained mesh
It marks product 39.1mg (0.13mmol).Yellow solid 2h, yield 26%.
Embodiment nine
BrCN (157.5mg, 1.5mmol) is added into reaction flask, under nitrogen protection, 1ml tetrahydro furan is added at 0 DEG C
It mutters.It is added in reaction flask after compound 1i (152.5mg, 0.5mmol) is dissolved in 2ml tetrahydrofuran and the mixing of 0.5mL triethylamine,
1h is reacted under room temperature.Reaction system, which chromatographs (eluant, eluent is methylene chloride: petroleum ether=1:8) by simple column, can be obtained mesh
It marks product 45.8mg (0.13mmol).Yellow solid 2i, yield 26.5%.
Embodiment ten
BrCN (157.5mg, 1.5mmol) is added into reaction flask, under nitrogen protection, 1ml tetrahydro furan is added at 0 DEG C
It mutters.It is added in reaction flask after compound 1j (192.5mg, 0.5mmol) is dissolved in 2ml tetrahydrofuran and the mixing of 0.5mL triethylamine,
1h is reacted under room temperature.Reaction system, which chromatographs (eluant, eluent is methylene chloride: petroleum ether=1:8) by simple column, can be obtained mesh
It marks product 63.6mg (0.15mmol).Yellow solid 2j, yield 30%.
The foregoing is merely section Examples of the invention, are not intended to limit the invention, it is all in spirit of the invention and
Within principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
The above embodiments are only the preferred technical solution of the present invention, and are not construed as limitation of the invention, this Shen
Please in embodiment and embodiment in feature in the absence of conflict, can mutual any combination.Protection model of the invention
The technical solution that should be recorded with claim is enclosed, the equivalent replacement side of technical characteristic in the technical solution recorded including claim
Case is protection scope.Equivalent replacement i.e. within this range is improved, also within protection scope of the present invention.
Claims (3)
1. a kind of preparation method of heterocyclic compound, which is characterized in that the compound is benzothiazole derivant, structural formula
Are as follows:
Wherein, substituent R1And R2It is not fixed for hydrogen or alkyl or nitro or halogen or aldehyde radical, substituting group position, number, the side
Method includes following synthesis path:
Method the following steps are included:
Bromination nitrile is added into reaction flask at room temperature, tetrahydrofuran is cooled to 0 DEG C, nitrogen protection；Compound 1 and triethylamine
It is dissolved in tetrahydrofuran, then is added drop-wise in mixture above-mentioned, then heat to 25-50 DEG C and be stirred to react 0.5-12h, carry out
Purification by filtration obtains compound 2, completes the synthesis of heterocyclic compound.
2. according to the method described in claim 1, it is characterized by: the feed ratio of the compound 1, bromination nitrile, triethylamine is
1:1-100:1-100.
3. according to the method described in claim 1, reaction 1 is small it is characterized by: the reaction condition is 25 DEG C of reaction temperature
When.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611109042.4A CN106699777B (en) | 2016-12-06 | 2016-12-06 | A kind of heterocycle compound and synthetic method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611109042.4A CN106699777B (en) | 2016-12-06 | 2016-12-06 | A kind of heterocycle compound and synthetic method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106699777A CN106699777A (en) | 2017-05-24 |
| CN106699777B true CN106699777B (en) | 2019-01-15 |
Family
ID=58936082
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611109042.4A Active CN106699777B (en) | 2016-12-06 | 2016-12-06 | A kind of heterocycle compound and synthetic method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106699777B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016209619A1 (en) * | 2015-06-23 | 2016-12-29 | Thesan Pharmaceuticals, Inc. | 12h-benzo[a]xanthen-12-ones, compositions containing, and uses of, same |
-
2016
- 2016-12-06 CN CN201611109042.4A patent/CN106699777B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016209619A1 (en) * | 2015-06-23 | 2016-12-29 | Thesan Pharmaceuticals, Inc. | 12h-benzo[a]xanthen-12-ones, compositions containing, and uses of, same |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106699777A (en) | 2017-05-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104910104B (en) | A kind of method of utilization copper catalysis synthesizing dihydro furan derivatives | |
| CN108794426B (en) | Heterocyclic dithiocarbamate compound and preparation method thereof | |
| CN102001979B (en) | Preparation method of 2-(2', 2'-difluoroethoxyl)-6-trifluoromethyl phenyl propyl sulfide | |
| CN103804432B (en) | Double-functionalized amine-thiourea organic catalyst based on ferrocene and preparation method and application thereof | |
| CN106699777B (en) | A kind of heterocycle compound and synthetic method | |
| Adib et al. | Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of 4, 5-diphenyl-1, 3-dihydro-2H-imidazol-2-one. One-pot synthesis of 5H-imidazo [2, 1-b][1, 3] oxazine derivatives | |
| CN105820202B (en) | A kind of avermectin derivatives and its preparation method and application | |
| CN115197153B (en) | Preparation method of 1, 4-diazacycloalkane compound | |
| CN109651385A (en) | A kind of preparation method of pyrans [3,2-a] carbazole compound | |
| CN103254191B (en) | Substituted aroma four lopps antifungal compound and preparation method thereof and application | |
| CN106397381B (en) | 2- alkoxy chromone 9 oxime derivate and the preparation method and application thereof | |
| CN104610267A (en) | Method for efficiently synthetizing 6-alkylpyrazol-[1,5-c]-quinazoline skeleton compounds under no catalytic condition | |
| CN105330590B (en) | The preparation method of sitafloxacin five-membered ring side chain intermediate | |
| CN110804012B (en) | Method for reducing mercaptal or thioketone for desulfurization | |
| CN103288757B (en) | Preparation method of 6-amino-7-hydroxyl-3,4-dihydroquinazoline-4-ketone | |
| CN110698422A (en) | Synthetic method of aromatic mercapto-diazole derivative | |
| CN102718694B (en) | 3-cyan substituted indole compound and synthetic method thereof | |
| CN108250152B (en) | 3, 4-dihydroquinazoline derivative with antibacterial activity and synthetic method and application thereof | |
| CN106316999B (en) | A kind of preparation method and application of two ketoximes derivatives of benzofuran -2,3- | |
| CN104860880A (en) | Method for synthesizing 8-(nitro methyl) quinoline compounds | |
| CN105646288A (en) | Preparation method of carbamate derivatives | |
| CN101544636A (en) | Polyhalogenated isoquinoline class derivate and synthetic method thereof | |
| CN104151274A (en) | Synthetic method for gamma-crotonolactone and derivative thereof | |
| CN105237432B (en) | The synthetic method of N, N di-2-ethylhexylphosphine oxide benzamide compound | |
| CN104860881A (en) | Methods for synthesizing 8-(nitro methyl) quinoline compounds and 8-methylamino tetrahydroquinoline compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220629 Address after: 445700 Lvshui Sihe Industrial Park, Laifeng County, Enshi Tujia and Miao Autonomous Prefecture, Hubei Province Patentee after: HUBEI LAIFENG TENGSHEN FLAVOR CHEMICAL Co.,Ltd. Address before: 443002 No. 8, University Road, Yichang, Hubei Patentee before: CHINA THREE GORGES University |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A Heterocyclic Compound and Its Synthesis Method Effective date of registration: 20230613 Granted publication date: 20190115 Pledgee: Hubei Laifeng Rural Commercial Bank Co.,Ltd. Pledgor: HUBEI LAIFENG TENGSHEN FLAVOR CHEMICAL Co.,Ltd. Registration number: Y2023420000229 |