A kind of free radical cyclization method of 1,6- enyne compounds and azo alkyl nitrile
阅读说明：本技术 一种1,6-烯炔类化合物与偶氮烷基腈的自由基环化反应方法 (A kind of free radical cyclization method of 1,6- enyne compounds and azo alkyl nitrile ) 是由 曹婷婷 魏文廷 黄训杰 宋思哲 于 2019-09-05 设计创作，主要内容包括：本发明涉及一种1,6-烯炔类化合物与偶氮烷基腈在温和条件下的区域选择性自由基环化反应方法。该方法通过向Schlenk反应瓶中加入1,6-烯炔类化合物、偶氮烷基腈类化合物、催化剂、碱和溶剂,在一定温度、空气气氛条件下搅拌反应,得到环化产物。(The present invention relates to one kind 1,6- enyne compounds and the regioselectivity free radical cyclization method of azo alkyl nitrile in a mild condition.This method is stirred to react under the conditions of certain temperature, air atmosphere by the way that 1,6- enyne compounds, azo alkyl nitrile compounds, catalyst, alkali and solvent are added into Schlenk reaction flask, obtains cyclisation product.)
1. one kind 1, the free radical cyclization method of 6- enyne compounds and azo alkyl nitrile, which is characterized in that including such as Lower step:
Be added into Schlenk reaction flask 1,6- yne compounds shown in formula 1, azo alkyl nitrile, catalyst shown in formula 2, Reaction flask is placed under the conditions of certain temperature, air atmosphere and is stirred to react by alkali and solvent, monitors reaction process through TLC or GC, until Raw material fully reacting, it is post-treated to obtain cyclisation product (I)；
In the compound that formula 1, formula 2 and Formulas I indicate, R1Selected from hydrogen, C5-C14Aryl, C1-C10Alkyl, C1-C6Acyl group；
R2Selected from hydrogen, C1-C6Alkyl, C5-C14Aryl；
R3Selected from C1-C8Alkyl, C5-C14Aryl；
R4Selected from C1-C6Alkyl, C5-C14Aryl；
R5Selected from C1-C6Alkyl, C5-C14Aryl；
Wherein, above-mentioned each R1-R5In substituent group there is the carbon atom number purpose aryl, alkyl and acyl group to be optionally substituted Base replaces, and the substituent group is selected from halogen, C1-C6Alkyl, C1-C6Alkoxy, C5-C14The C that aryl, halogen replace1-C6Alkane Base ,-NO2、-CN、C1-C6Alkyl-C (=O)-, C1-C6Alkyl-OC (O=)-.
2. the method according to claim 1, wherein R1Selected from C1-C10Alkyl, C5-C14Aryl；The wherein C1- C10Alkyl, C5-C14Aryl is optionally substituted base substitution, and the substituent group is selected from halogen, C1-C6Alkyl, C1-C6Alkoxy, C5-C14The C that aryl, halogen replace1-C6Alkyl ,-NO2、-CN、C1-C6Alkyl-C (=O)-, C1-C6Alkyl-OC (O=)-；
R2Selected from hydrogen；
R3Selected from hydrogen, C1-C8Alkyl, C5-C14Aryl, wherein the C1-C6Alkyl, C5-C14Aryl is optionally substituted base substitution, The substituent group is selected from halogen, C1-C6Alkyl, C1-C6Alkoxy, C5-C14The C that aryl, halogen replace1-C6Alkyl ,-NO2、- CN、C1-C6Alkyl-C (=O)-, C1-C6Alkyl-OC (O=)-；
R4Selected from C1-C6Alkyl；
R5Selected from C1-C6Alkyl.
3. method described in -2 any one according to claim 1, which is characterized in that the catalyst be selected from cuprous iodide, Cuprous bromide, stannous chloride, copper bromide, any one or a few the mixture in copper acetate, preferably cuprous iodide.
4. method according to claim 1 to 3, which is characterized in that the alkali is selected from triethylamine, 1,8- bis- 11 carbon -7- alkene of azabicyclic, potassium acetate, any one or a few the mixture in tetra-n-butyl ammonium acetate, preferably three Ethamine.
5. method according to any of claims 1-4, which is characterized in that the solvent is in acetonitrile, water Any one or a few mixture, the solvent are preferably H2O/MeCN (v: v=4: 1,2.0mL).
6. method described in -5 any one according to claim 1, which is characterized in that the certain temperature is 40-80 DEG C, excellent It is selected as 60 DEG C.
7. method described in -6 any one according to claim 1, which is characterized in that 1, the 6- yne compounds of formula 1 and formula 2 The molar ratio of azo alkyl nitrile is 1: 1.2~1: 3, it is preferable that the azo alkyl nitrile of 1, the 6- yne compounds and formula 2 of formula 1 Molar ratio is 1: 2.
8. method described in -7 any one according to claim 1, which is characterized in that the post-processing operation is as follows: will be anti- Reaction solution after the completion of answering is extracted with ethyl acetate, and organic phase dries, filters with anhydrous sodium sulfate and be concentrated under reduced pressure removing solvent, By residue through column chromatography for separation, eluting solvent are as follows: ethyl acetate/n-hexane obtains the cyclisation product (I) of target.
Technical field
The application belongs to organic synthesis field, and in particular to one kind 1,6- enyne compounds are with azo alkyl nitrile mild Under the conditions of regioselectivity free radical cyclization method.
Background technique
In polymer chemistry, azo alkyl nitrile is widely used as radical initiator.Traditionally, only cause free radical Process, and it is not involved in chemical reaction.In recent years, in the system existing for copper catalysis and/or oxidant, azo alkyl nitrile energy conduct A kind of cyanylation agent use of safety and low toxicity.In this context, chemists developed azo alkyl nitrile and alkene, alkynes and The cyanalation reaction of eneyne derivative.However, azo alkyl nitrile is after occurring cyanalation reaction further by intramolecular cyclization Reaction is but rarely reported to participate in radical cycloaddition reaction as double carbon units.
The free radical cyclization that inventor participates in azo alkyl nitrile under temperate condition conducts in-depth research, In In the present invention, we have proposed one kind with 1,6- enyne compounds and azo alkyl nitrile for reaction raw materials, cheap and easy to get Under catalyst and base catalysis system through the high regioselectivity of free radical process it is cyanalation/new method of cyclization.
Summary of the invention
The purpose of the present invention is to overcome the deficiency in the prior art, provides a kind of green high-efficient, low cost, highly selective 1, Cyanalation/cyclization method of 6- enyne compounds and azo alkyl nitrile, this method are highly selective in a mild condition Cyclisation product is prepared with higher yields.
Free radical cyclization method provided by the invention, this method are with 1,6- enyne compounds and azo alkyl nitrile Raw material is prepared through the following steps:
1,6- yne compounds shown in formula 1, azo alkyl nitrile shown in formula 2, catalysis are added into Schlenk reaction flask Reaction flask is placed under the conditions of certain temperature, air atmosphere and is stirred to react by agent, alkali and solvent, through TLC or GC monitoring react into Journey, until raw material fully reacting, post-treated to obtain cyclisation product (I).
1,6- eneyne provided by the invention and the highly selective free radical cyclization method of azo alkyl nitrile, chemical reaction Formula can be expressed as (see formula one):
In the reaction of above-mentioned formula one, the reaction atmosphere is the air atmosphere of 1atm, also could alternatively be the nitrogen of 1atm Gas atmosphere or other inert gas atmospheres consider, preferably air atmosphere from economic cost etc..
The post-processing operation is as follows: reaction solution after the reaction was completed being extracted with ethyl acetate, organic phase is with anhydrous Sodium sulphate dries, filters and is concentrated under reduced pressure removing solvent, by residue through column chromatography for separation, eluting solvent are as follows: and ethyl acetate/just Hexane obtains the cyclisation product (I) of target.
In the compound that formula 1, formula 2 and Formulas I indicate, R1Selected from hydrogen, C5-C14Aryl, C1-C10Alkyl, C1-C6Acyl group；
R2Selected from hydrogen, C1-C6Alkyl, C5-C14Aryl；
R3Selected from C1-C8Alkyl, C5-C14Aryl；
R4Selected from C1-C6Alkyl, C5-C14Aryl；
R5Selected from C1-C6Alkyl, C5-C14Aryl；
Wherein, above-mentioned each R1-R5In substituent group have the carbon atom number purpose aryl, alkyl and acyl group optionally by Substituent group replaces, and the substituent group is selected from halogen, C1-C6Alkyl, C1-C6Alkoxy, C5-C14The C that aryl, halogen replace1-C6 Alkyl ,-NO2、-CN、C1-C6Alkyl-C (=O)-, C1-C6Alkyl-OC (O=)-.
Preferably, R1Selected from C1-C10Alkyl, C5-C14Aryl；The wherein C1-C10Alkyl, C5-C14Aryl optionally by Substituent group replaces, and the substituent group is selected from halogen, C1-C6Alkyl, C1-C6Alkoxy, C5-C14The C that aryl, halogen replace1-C6Alkane Base ,-NO2、-CN、C1-C6Alkyl-C (=O)-, C1-C6Alkyl-OC (O=)-；
R2Selected from hydrogen；
R3Selected from hydrogen, C1-C8Alkyl, C5-C14Aryl, wherein the C1-C6Alkyl, C5-C14Aryl is optionally substituted base Replace, the substituent group is selected from halogen, C1-C6Alkyl, C1-C6Alkoxy, C5-C14The C that aryl, halogen replace1-C6Alkyl ,- NO2、-CN、C1-C6Alkyl-C (=O)-, C1-C6Alkyl-OC (O=)-；
R4Selected from C1-C6Alkyl；
R5Selected from C1-C6Alkyl.
In the reaction of the present invention, the catalyst is selected from cuprous iodide, cuprous bromide, stannous chloride, copper bromide, vinegar Any one or a few mixture in sour copper, preferably cuprous iodide.
In the reaction of the present invention, the alkali be selected from triethylamine, 1,8- diazabicylo, 11 carbon -7- alkene, potassium acetate, Any one or a few mixture in tetra-n-butyl ammonium acetate, preferably triethylamine.
In the reaction of the present invention, any one or a few mixture of the solvent in acetonitrile, water, it is described Solvent be preferably H2O/MeCN (v: v=4: 1,2.0mL).
In the reaction of the present invention, the certain temperature is 40-80 DEG C, and temperature is most preferably 60 DEG C.
In the reaction of the present invention, the molar ratio of the azo alkyl nitrile of 1, the 6- yne compounds and formula 2 of the formula 1 is 1: 1.2~1: 3.Preferably, the molar ratio of the azo alkyl nitrile of 1, the 6- yne compounds and formula 2 of formula 1 is 1: 2.
The beneficial effects of the present invention are: proposing 1,6- yne compounds and the free basic ring of azo alkyl nitrile under temperate condition Change reaction method, this method is freely cyclization by intramolecular twice, to obtain a series of target product in high yield.This method Have the advantages that reaction substrate adaptation range is extensive, be simple and efficient, particularly suitable for industrialized production.
Specific embodiment
Below in conjunction with specific embodiment, further detailed description is carried out to the present invention, but the present invention is not limited thereto.
Experimental method described in following embodiments is unless otherwise specified conventional method；The reagent and raw material, such as Without specified otherwise, it can obtain and/or prepare according to known methods from commercial channels.
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