CN105130863A - Synthetic method of novel N-methylated sulfoximine derivative - Google Patents
Synthetic method of novel N-methylated sulfoximine derivative Download PDFInfo
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- CN105130863A CN105130863A CN201510437621.0A CN201510437621A CN105130863A CN 105130863 A CN105130863 A CN 105130863A CN 201510437621 A CN201510437621 A CN 201510437621A CN 105130863 A CN105130863 A CN 105130863A
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Abstract
A simple, clean and high-effective synthetic method of a novel N-methylated sulfoximine derivative is provided in the invention. The invention relates to the fields of pesticides, organic chemical engineering and fine chemical engineering. The method essentially is an organic synthesis reaction that a methyl free radical, which is generated from peroxides, and a sulfoximine compound are subjected to free radical coupling to form new C-N bonds. The method includes the step of carrying out a reaction to obtain the N-methylated sulfoximine derivative in a common organic solvent under a heating condition from the raw materials including diphenyl sulfoximine and a methylating reagent (peroxides) under the catalysis by copper. The method is 2-20 h in reaction time under a heating and stirring condition. The molar ratio of the raw materials is that the diphenyl sulfoximine to the methylating reagent is 1:0.5-3.0. The raw materials are reacted under the heating condition and then reaction products are subjected to simple after treatments to obtain the N-methylated sulfoximine derivative at a yield being 36-87%. The invention develops a series of N-methylating methods based on a free radical process to prepare a series of N-methylated sulfoximine derivatives. The method is simple in operation and after treatments, and is simple and practical in synthesis of these compounds.
Description
Technical field
The present invention relates to agricultural chemicals, organic chemical industry and field of fine chemical, be related specifically to a kind of by the carbonnitrogen bond forming reactions of superoxide as methylating reagent, is that a kind of novel N-methylates sulphoxide imine derivative synthesizing process.
Background technology
Methyl group as the very important functional group of a class, in the middle of the molecule being present in many drug molecules and natural product widely.The introducing of methyl group, obviously can improve solvability and the physiologically active of molecule.Traditional methylated method mainly concentrates on and utilizes methyl iodide or methyl boron reagent etc. to be methylating reagent, but these traditional methylating reagents have toxic, volatile, the unstable or drawback that easily causes environmental pollution many.In recent years, flourish along with free-radical chemistry, a new stage has been stepped in the research of methylation reaction.Reporting from the seminar of Li in 2008 has utilized dicumyl peroxide as [Zhang, Y. since methylating reagent; Feng, J.; Li, C.-J.J.Am.Chem.Soc.2008,130,2900.], increasing organic chemist joins in the methylation reaction how utilizing the method by generating methyl free radicals to realize organic compound.
Sulphoxide imine compounds is the core skeleton of very important agricultural chemical insecticide and medical molecule.Meanwhile, can also asymmetry catalysis synthesis be used for as part and realize the activation of c h bond as homing device.In addition, sulphoxide imine class substrate can also as the intermediate building aromatic ring frame.There are many reports for the nitrogen-atoms of this kind of substrate carrying out functionalization in recent years, but fewer all the time for sulphoxide imine compound nitrogen-atoms carrying out methylated report.Can realize at present sulphoxide imine class substrate nitrogen-atoms carries out methylated method, mainly utilize formic acid, formaldehyde and sulfuric acid, under the condition of backflow, super the time obtains methylated product two days later in reaction.This kind of method, long reaction time, and used this kind of toxic substance of formaldehyde.
Therefore, for how finding one rapidly and efficiently, and nontoxic, one of method simple to operate problem of always being that the educational circles that organises urgently saves of methylating realizing sulphoxide imine nitrogen-atoms.And in whether can being applied to for sulphoxide imine substrate the methylated reaction of N-as a kind of method studying the very popular methyl free radicals utilizing superoxide to produce in recent years be worth we pay close attention to.
Our research is exactly with diphenyl sulfoxide imines for substrate, and experience free radical proceed, treats different things alike, and occurs to build the reaction of carbonnitrogen bond, obtains a series of N-and to methylate sulphoxide imine derivative.
The present invention adopts diphenyl sulfoxide imines and peroxide reactions, and under the condition of copper catalysis, preparation N-methylates sulphoxide imine compounds.Compared with the preparation method in document, this experimentation reaction times is shorter, avoids using poisonous chemical reagent, has the tolerance of reasonable functional group simultaneously; Reaction efficiency is high; Reaction conditions is gentle, radical initiator (methylating reagent) low price, and separating-purifying is convenient, and waste discharge is few, and to the substrate of reaction without particular requirement, the plurality of advantages such as applied widely, has very high using value.
Summary of the invention
Technical problem solved by the invention is to provide a kind of radical initiator that simply utilizes and methylates the approach of sulphoxide imine for methylating reagent forms N-.The method is easy and simple to handle, is that a kind of efficient radical mechanism synthesis N-methylates the reaction of sulphoxide imine derivative.
The invention relates to a kind of N-to methylate the preparation method of sulphoxide imine, with diphenyl sulfoxide imines and superoxide for raw material, after adding copper catalyst and appropriate organic solvent, stirring reaction, the linked reaction synthesis N-being formed carbonnitrogen bond by free radical is methylated sulphoxide imine compounds.Reaction conditions is: air or in protection of inert gas, and under the condition of heating, the reaction times is 2-20 hour.
Described methylating reagent is the one in the common superoxide such as tertbutyl peroxide, dicumyl peroxide, peroxidized t-butyl perbenzoate.
The consumption of described radical initiator is 0.5-3.0 times of diphenyl sulfoxide imines mole number.
Described catalyzer mol ratio is thionyl benzene imines: catalyzer=1:0.1.
Described solvent is acetonitrile, benzene, DMF, fluorobenzene, chlorobenzene etc.Solvent load is 10mL/mmol diphenyl sulfoxide imines.
Substituting group on two aromatic rings of described raw material diphenyl sulfoxide imines can be methyl, methoxyl group, bromine, chlorine, benzene etc., can both obtain corresponding product.
The N-sulphoxide imine class product that methylates can under the above-described reaction conditions, generate smoothly.
Described post-reaction treatment is easy, only needs simple pillar layer separation method, to methylate sulphoxide imine product for eluent just can obtain pure N-with the mixed solvent of sherwood oil and ethyl acetate.
The present invention is better than the synthetic method reported in document, and the reaction times is short, avoids the reagent using toxicity large, is that methylating reagent green is clean with superoxide.。
Embodiment
Embodiment 1
Thionyl benzene imines 1a (2mmol), tertbutanol peroxide (4mmol) are mixed with cupric chloride (0.2mmol), adding chlorobenzene 20mL is solvent, and react under heating state, the reaction times experiences 4 hours.The transformation efficiency of thionyl benzene imines is the productive rate of 96%, 3a is 85%.
Embodiment 2
By 4,4 '-dimethyl thionyl benzene imines 1b (2mmol), dicumyl peroxide (1mmol) mix with cupric bromide (0.2mmol), adding fluorobenzene 20mL is solvent, and react under heating state, the reaction times experiences 2 hours.1b transformation efficiency is the productive rate of 89%, 3b is 77%.
Embodiment 3
By 4,4 '-dichloro sulphoxide imine 1c (2mmol), peroxidized t-butyl perbenzoate (6mmol) mix with cupric chloride (0.2mmol), adding toluene 20mL is solvent, and react under heating state, the reaction times experiences 16 hours.The transformation efficiency of 1c is the productive rate of 92%, 3c is 74%.
Embodiment 4
4-methyldiphenyl sulphoxide imine 1d (2mmol), dicumyl peroxide (4mmol) are mixed with cupric chloride (0.2mmol), adding acetonitrile 20mL is solvent, and react under heating state, the reaction times experiences 16 hours.The transformation efficiency of 1d is the productive rate of 92%, 3d is 59%.
Embodiment 5
4-phenyl thionyl benzene imines 1e (2mmol), tertbutanol peroxide (3mmol) are mixed with cuprous iodide (0.2mmol), adding benzene 20mL is solvent, and react under heating state, the reaction times experiences 6 hours.The transformation efficiency of 1e is the productive rate of 98%, 3e is 87%.
Embodiment 6
4-methoxyl group thionyl benzene imines 1f (2mmol), dicumyl peroxide (6mmol) are mixed with copper sulfate (0.2mmol), adding acetone 20mL is solvent, and react under heating state, the reaction times experiences 9 hours.The transformation efficiency of 1f is the productive rate of 98%, 3f is 81%.
Embodiment 7
4-bromine thionyl benzene imines 1g (2mmol), di-t-butyl peroxide (1mmol) are mixed with cupric chloride (0.2mmol), add N, dinethylformamide 20mL is solvent, reacts under heating state, and the reaction times experiences 20 hours.The transformation efficiency of 1g is the productive rate of 89%, 3g is 59%.
Embodiment 8
Bromo-for 4-2 '-methyldiphenyl sulphoxide imine 1h (2mmol), dicumyl peroxide (6mmol) are mixed with cupric chloride (0.2mmol), adding benzene sulfone 20mL is solvent, react under heating state, the reaction times experiences 8 hours.The transformation efficiency of 1h is the productive rate of 96%, 3h is 43%.
Embodiment 9
4-ethanoyl thionyl benzene imines 1i (2mmol), tertbutanol peroxide (4mmol) are mixed with cupric bromide (0.2mmol), adding chlorobenzene 20mL is solvent, and react under heating state, the reaction times experiences 12 hours.The transformation efficiency of 1i is the productive rate of 89%, 3i is 51%.
Embodiment 10
By 4-methyl-4 '-phenyl thionyl benzene imines 1j (2mmol), dicumyl peroxide (5mmol) mix with cuprous iodide (0.2mmol), adding chlorobenzene 20mL is solvent, react under heating state, the reaction times experiences 2 hours.The transformation efficiency of 1j is the productive rate of 95%, 3j is 62%.
Embodiment 11
By 4-methyl-4 '-bromine thionyl benzene imines 1k (2mmol), peroxidized t-butyl perbenzoate (6mmol) mix with copper sulfate (0.2mmol), adding acetonitrile 20mL is solvent, react under heating state, the reaction times experiences 12 hours.The transformation efficiency of 1k is the productive rate of 99%, 3k is 93%.
Embodiment 12
Phenylcyclohexyl sulphoxide imine 1l (2mmol), tertbutanol peroxide (6mmol) are mixed with cupric chloride (0.2mmol), add N, dinethylformamide 20mL is solvent, reacts under heating state, and the reaction times experiences 20 hours.The transformation efficiency of 1l is the productive rate of 89%, 3l is 73%.
Embodiment 13
Phenyl methyl sulphoxide imine 1m (2mmol), dicumyl peroxide (2mmol) are mixed with cupric chloride (0.2mmol), adding chlorobenzene 20mL is solvent, and react under heating state, the reaction times experiences 4 hours.The transformation efficiency of 1m is the productive rate of 95%, 3m is 65%.
Embodiment 14
Phenylethyl sulphoxide imine 1n (2mmol), peroxidized t-butyl perbenzoate (6mmol) are mixed with neutralized verdigris (0.2mmol), adding acetonitrile 20mL is solvent, and react under heating state, the reaction times experiences 8 hours.The transformation efficiency of 1n is the productive rate of 86%, 3n is 42%.
Embodiment 15
Phthalic imidine 1o (2mmol), tertbutanol peroxide (6mmol) are mixed with copper sulfate (0.2mmol), add N, dinethylformamide 20mL is solvent, reacts under heating state, and the reaction times experiences 13 hours.The transformation efficiency of 1o is the productive rate of 51%, 3o is 36%.
Advantage of the present invention
Synthesized the methylate method of sulphoxide imine of N-all to relate to use formaldehyde and formic acid to react 2 to 3 days in a heated condition in the past, reaction efficiency is poor, and raw materials used poisonous and do not meet the theory of environmental protection, react for very multi-functional tolerance in acid condition is also a larger test simultaneously.Our strategy utilizes radical mechanism, is that methyl is originated with superoxide, utilizes cheap copper catalyst to impel carbonnitrogen bond generation linked reaction, practical.
Claims (7)
1. a novel N-methylates the synthetic method of sulphoxide imine derivative; it is characterized in that reaction is carried out according to following steps: mixed with superoxide by diphenyl sulfoxide imines; add copper catalyst and a small amount of solvent; in room temperature to 150 DEG C; air or react under protection of inert gas; stopped reaction after lasting 2-20 hour, simple process high yield can obtain target product N-and to methylate sulphoxide imine, and productive rate is 36-87%.
2. a kind of novel N-according to claim 1 methylates the synthetic method of sulphoxide imine derivative, it is characterized in that the molar weight of wherein said diphenyl sulfoxide imines and superoxide (methylating reagent) than being 1:0.5-3.0.
3. a kind of novel N-according to claim 1 methylates the synthetic method of sulphoxide imine derivative, it is characterized in that wherein used radical initiator (methylating reagent) can be di-t-butyl peroxide, tertbutyl peroxide, dicumyl peroxide, peroxidized t-butyl perbenzoate etc.
4. a kind of novel N-according to claim 1 methylates the synthetic method of sulphoxide imine derivative, it is characterized in that used solvent is acetonitrile, benzene, DMF, tetrahydrofuran (THF), chlorobenzene etc.
5. the catalyzer mol ratio stated according to claim 1 be thionyl benzene imines: catalyzer=1:0.1.
6. the catalyzer stated according to claim 1 can be cupric chloride, copper sulfate, cupric bromide, cuprous iodide etc.
7. a kind of novel N-according to claim 1 methylates the synthetic method of sulphoxide imine derivative, it is characterized in that the substrate applicability reacted is comparatively wide, good yield can both be obtained for containing the substituent diaryl sulphoxide imines such as methyl, methoxyl group, chlorine, bromine, phenyl etc.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106278970A (en) * | 2016-08-09 | 2017-01-04 | 孙冉 | A kind of synthetic method of diaryl sulphoxide aminated compounds |
| CN109390631A (en) * | 2018-09-30 | 2019-02-26 | 东莞东阳光科研发有限公司 | A kind of nickelic tertiary cathode material electrolyte |
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2015
- 2015-07-23 CN CN201510437621.0A patent/CN105130863B/en active Active
Non-Patent Citations (3)
| Title |
|---|
| CARL R. JOHNSON, ET AL.: "Preparation of a-Halo Sulfoximines", 《J. ORG. CHEM.》 * |
| HUI ZHU, ET AL.: "Radical N-arylation/alkylation of sulfoximines", 《TETRAHEDRON LETTERS》 * |
| YING CHENG, ET AL.: "Iron-Catalyzed Hetero-Cross-Dehydrogenative Coupling Reactions of Sulfoximines with Diarylmethanes: A New Route to N‑Alkylated Sulfoximines", 《ORGANIC LETTERS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106278970A (en) * | 2016-08-09 | 2017-01-04 | 孙冉 | A kind of synthetic method of diaryl sulphoxide aminated compounds |
| CN109390631A (en) * | 2018-09-30 | 2019-02-26 | 东莞东阳光科研发有限公司 | A kind of nickelic tertiary cathode material electrolyte |
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