CN106431800B - (E) synthetic method of -4- oxo -2- butylene aldehyde compound - Google Patents

(E) synthetic method of -4- oxo -2- butylene aldehyde compound Download PDF

Info

Publication number
CN106431800B
CN106431800B CN201610735202.XA CN201610735202A CN106431800B CN 106431800 B CN106431800 B CN 106431800B CN 201610735202 A CN201610735202 A CN 201610735202A CN 106431800 B CN106431800 B CN 106431800B
Authority
CN
China
Prior art keywords
added
oxo
ethyl acetate
dry
reaction
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
Application number
CN201610735202.XA
Other languages
Chinese (zh)
Other versions
CN106431800A (en
Inventor
范学森
何艳
张新迎
田苗苗
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Henan Normal University
Original Assignee
Henan Normal University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Henan Normal University filed Critical Henan Normal University
Priority to CN201610735202.XA priority Critical patent/CN106431800B/en
Publication of CN106431800A publication Critical patent/CN106431800A/en
Application granted granted Critical
Publication of CN106431800B publication Critical patent/CN106431800B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/06—Formation or introduction of functional groups containing oxygen of carbonyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C07D213/50—Ketonic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

The invention discloses it is a kind of (E) -4- oxo -2- butylene aldehyde compound synthetic method, belong to the synthesis technical field of aldehyde compound.Technical solution of the present invention main points are：Will (E)-4- nitro-2- butene-1 -one class compound 1 is dissolved in organic solvent, and oxidant is then added, be made in air or oxygen atmosphere in 40-100 DEG C of reaction (E) -4- oxo -2- butylene aldehyde compound 2.Synthesis process of the present invention is single step reaction, and method is simple, and raw material is easily prepared, and reaction is carried out at 100 DEG C or less, and mild condition is easy to operate, applied widely, the product configuration stereoselectivity height of substrate.

Description

(E) synthetic method of -4- oxo -2- butylene aldehyde compound
Technical field
The invention belongs to technical field of organic synthesis, and in particular to one kind (E) -4- oxo -2- butylene aldehyde compound Synthetic method.
Background technique
4- oxo -2- crotonaldehyde belongs to Isosorbide-5-Nitrae-dicarbapentaborane class compound, is having because having active, multiplicity reactivity worth The fields such as machine synthesis, medicine, chemical industry and material have important application value.Currently, the method for synthesis 4- oxo -2- crotonaldehyde The oxygen of the main hydrolysis including acid catalysis dimethoxy dihydrofuran, furan derivatives or 2- butylene-1,4-diol class compound The intermolecular cross-coupling and palladium chtalyst acyl chlorides and tin of change, 1,3- dicarbonyl compound and methyl ketone are for ketene compounds Reductive coupling reaction etc..The above method although 4- oxo -2- butylene aldehyde compound can be synthesized effectively, there are still it is some not Foot place, if you need to use, the mixture of noble metal catalyst, different stereoisomers easily generated, functional group compatibility is poor, reacts Condition is violent, reaction step is cumbersome etc., so that the practicality be made to be restricted.Therefore, it is necessary to further study and develop 4- oxygen The simplicity of generation -2- butylene aldehyde compound, efficiently synthesizes new method at economy.
Summary of the invention
The technical problem to be solved by the present invention is to provide the synthesis sides of one kind (E) -4- oxo -2- butylene aldehyde compound Method, the synthetic method is from the raw material simply easily prepared, by single step reaction, directly obtains (E) -4- oxo -2- crotonaldehyde Class compound, easy to operate, mild condition, wide application range of substrates are suitable for industrialized production.
The present invention adopts the following technical scheme that solve above-mentioned technical problem, (E) -4- oxo -2- butylene aldehyde compound Synthetic method, it is characterised in that：(E)-4- nitro-2- butene-1 -one class compound 1 is dissolved in organic solvent, then plus Enter oxidant, is reacted in air or oxygen atmosphere in 40-100 DEG C and (E) -4- oxo -2- butylene aldehyde compound 2 is made, it should Reaction equation in synthetic method is：
Wherein R1For 1- naphthalene, 4- pyridyl group, 2- thienyl, phenyl or substituted-phenyl, taking on the substituted-phenyl phenyl ring One of Dai Jiwei fluorine, chlorine, bromine, methyl, trifluoromethyl or methoxyl group are a variety of, and the position of substituent group is the neighbour on phenyl ring Position, meta or para position, R2For hydrogen, alkyl or phenyl, R3For hydrogen or alkyl, oxidant is tetramethyl piperidine nitrogen oxides (TEMPO), di-tert-butyl peroxide (TBP) or manganese dioxide (MnO2), organic solvent is toluene, acetonitrile, Isosorbide-5-Nitrae dioxane Or dichloroethanes.
It further limits, the substance that feeds intake of (E)-4- nitro-2- butene-1 -one class compound 1 and oxidant The ratio between amount is 1:0.5-2.
Compared with the prior art, the present invention has the following advantages：(1) synthesis process is single step reaction, and method is simple；(2) former Expect easily prepared；(3) reaction is carried out at 100 DEG C or less, and mild condition is easy to operate；(4) substrate is applied widely；(5) it produces Object configuration stereoselectivity is high.Therefore, the present invention provides a kind of warp for the synthesis of (E) -4- oxo -2- butylene aldehyde compound Ji, practical, green new method.
Specific embodiment
Above content of the invention is described in further detail by the following examples, but this should not be interpreted as to this The range for inventing above-mentioned theme is only limitted to embodiment below, and all technologies realized based on above content of the present invention belong to this hair Bright range.
Embodiment 1
1a (0.5mmol, 96mg) and dichloroethanes (DCE, 3mL) are added in the reaction flask of 25mL, TEMPO is then added (0.5mmol,78mg).It is stirred to react under oxygen (1atm) atmosphere in 70 DEG C 10 hours, it is molten that 8mL saturated sodium-chloride is then added Liquid quenching reaction is extracted with ethyl acetate (8mL × 3), merges organic phase, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel Post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- phenyl -2- crotonaldehyde 2a (72mg, 90%).The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:7.00(dd,J1=16.0Hz, J2= 7.6Hz, 1H), 7.54 (t, J=7.6Hz, 2H), 7.66 (t, J=7.6Hz, 1H), 7.72 (d, J=15.6Hz, 1H), 7.99 (d, J=7.2Hz, 2H), 9.90 (d, J=7.6Hz, 1H)13C NMR(150MHz,CDCl3)δ:128.9,129.1,134.2, 136.3,139.2,142.1,189.8,192.8.MS:m/z 161[MH]+。
Embodiment 2
By method described in embodiment 1,1a (0.5mmol, 96mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react in 70 DEG C 10 hours, is then added in air atmosphere 8mL saturated sodium chloride solution quenching reaction, is extracted with ethyl acetate (8mL × 3), merges organic phase, and anhydrous sodium sulfate is dry.It crosses Filter, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- phenyl -2- is obtained Crotonaldehyde 2a (61mg, 76%).
Embodiment 3
By method described in embodiment 1,1a (0.5mmol, 96mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under nitrogen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- benzene is obtained Base -2- crotonaldehyde 2a (16mg, 20%).
Embodiment 4
By method described in embodiment 1,1a (0.5mmol, 96mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (1mmol, 156mg) is added in (3mL).It is stirred to react in air atmosphere in 70 DEG C 10 hours, 8mL is then added Saturated sodium chloride solution quenching reaction is extracted with ethyl acetate (8mL × 3), merges organic phase, and anhydrous sodium sulfate is dry.Filtering, It is spin-dried for, crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- phenyl -2- fourth is obtained Olefine aldehydr 2a (70mg, 88%).
Embodiment 5
By method described in embodiment 1,1a (0.5mmol, 96mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.25mmol, 39mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, so 8mL saturated sodium chloride solution quenching reaction is added afterwards, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- is obtained Phenyl -2- crotonaldehyde 2a (44mg, 55%).
Embodiment 6
By method described in embodiment 1,1a (0.5mmol, 96mg) and dichloroethanes are added in the reaction flask of 25mL Then TBP (0.5mmol, 58 μ L) are added in (3mL).Be stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then plus Enter 8mL saturated sodium chloride solution quenching reaction, be extracted with ethyl acetate (8mL × 3), merge organic phase, anhydrous sodium sulfate is dry. Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- phenyl-is obtained 2- crotonaldehyde 2a (16mg, 20%).
Embodiment 7
By method described in embodiment 1,1a (0.5mmol, 96mg) and dichloroethanes are added in the reaction flask of 25mL (3mL), is then added MnO2(0.5mmol,44mg).It is stirred to react in air atmosphere in 70 DEG C 10 hours, 8mL is then added Saturated sodium chloride solution quenching reaction is extracted with ethyl acetate (8mL × 3), merges organic phase, and anhydrous sodium sulfate is dry.Filtering, It is spin-dried for, crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- phenyl -2- fourth is obtained Olefine aldehydr 2a (13mg, 16%).
Embodiment 8
By method described in embodiment 1,1a (0.5mmol, 96mg) and toluene (3mL) are added in the reaction flask of 25mL, Then TEMPO (0.5mmol, 78mg) is added.It is stirred to react 10 hours under oxygen (1atm) atmosphere in 70 DEG C, is then added 8mL saturated sodium chloride solution quenching reaction, is extracted with ethyl acetate (8mL × 3), merges organic phase, and anhydrous sodium sulfate is dry.It crosses Filter, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- phenyl -2- is obtained Crotonaldehyde 2a (56mg, 70%).
Embodiment 9
By method described in embodiment 1,1a (0.5mmol, 96mg) and acetonitrile (3mL) are added in the reaction flask of 25mL, Then TEMPO (0.5mmol, 78mg) is added.It is stirred to react 10 hours under oxygen (1atm) atmosphere in 70 DEG C, is then added 8mL saturated sodium chloride solution quenching reaction, is extracted with ethyl acetate (8mL × 3), merges organic phase, and anhydrous sodium sulfate is dry.It crosses Filter, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- phenyl -2- is obtained Crotonaldehyde 2a (49mg, 61%).
Embodiment 10
By method described in embodiment 1,1a (0.5mmol, 96mg) and Isosorbide-5-Nitrae-dioxy six are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in ring (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, so 8mL saturated sodium chloride solution quenching reaction is added afterwards, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- is obtained Phenyl -2- crotonaldehyde 2a (45mg, 56%).
Embodiment 11
By method described in embodiment 1,1a (0.5mmol, 96mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 40 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- benzene is obtained Base -2- crotonaldehyde 2a (42mg, 52%).
Embodiment 12
By method described in embodiment 1,1a (0.5mmol, 96mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 100 DEG C under oxygen (1atm) atmosphere, so 8mL saturated sodium chloride solution quenching reaction is added afterwards, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product (E) -4- oxo -4- is obtained Phenyl -2- crotonaldehyde 2a (66mg, 83%).
Embodiment 13
By method described in embodiment 1,1b (0.5mmol, 135mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product 2b (106mg, 89%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:6.74(dd,J1=15.6Hz, J2=7.6Hz, 1H), 7.36 (d, J=16.0Hz, 1H), 7.39-7.47 (m, 3H), 7.66 (d, J=7.6Hz, 1H), 9.88 (d, J=7.6Hz, 1H) .13C NMR(150MHz,CDCl3)δ:119.7,127.8,129.8,132.8,133.8,139.2,139.3,144.2,192.9, 193.5.MS:m/z 239[MH]+。
Embodiment 14
By method described in embodiment 1,1c (0.5mmol, 113mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product 2c (83mg, 86%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:7.00(dd,J1=15.6Hz, J2=7.2Hz, 1H), 7.49 (t, J=8.0Hz, 1H), 7.62-7.85 (m, 2H), 7.86 (d, J=8.0Hz, 1H), 7.96 (d, J=1.6Hz, 1H), 9.90 (d, J=7.2Hz, 1H)13C NMR(100MHz,CDCl3)δ:126.9,128.8,130.4,134.1,135.4, 137.8,139.6,141.1,188.5,192.5.MS:m/z 195[MH]+。
Embodiment 15
By method described in embodiment 1,1d (0.5mmol, 103mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product 2d (80mg, 92%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.39(s,3H),6.93(dd,J1=16.0Hz, J2 =7.6Hz, 1H), 7.26 (d, J=8.0Hz, 2H), 7.66 (d, J=15.6Hz, 1H), 7.84 (d, J=8.8Hz, 2H), 9.83 (d, J=7.6Hz, 1H)13C NMR(100MHz,CDCl3)δ:21.8,129.1,129.8,133.9,138.9,142.5, 145.4,189.3,192.9.MS:m/z 175[MH]+。
Embodiment 16
By method described in embodiment 1,1e (0.5mmol, 105mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product 2e (72mg, 81%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:6.94(dd,J1=15.6Hz, J2=7.2Hz, 1H), 7.14 (t, J=7.6Hz, 2H), 7.63 (d, J=15.6Hz, 1H), 7.96-7.99 (m, 2H), 9.82 (d, J=7.2Hz, 1H) .13C NMR(100MHz,CDCl3)δ:116.2(d,2JC-F=22.3Hz), 131.6 (d,3JC-F=9.8Hz), 132.7 (d,4JC-F =3.0Hz), 139.2,141.6,166.4 (d,1JC-F=254.9Hz), 188.2,192.6.MS:m/z 179[MH]+。
Embodiment 17
By method described in embodiment 1,1f (0.5mmol, 126mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=10:1) yellow liquid product 2f (90mg, 82%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:3.96(s,3H),3.97(s,3H),6.92-7.02 (m, 2H), 7.57 (d, J=2.0Hz, 1H), 7.63 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.74 (d, J=15.6Hz, 1H), 9.87 (d, J=7.6Hz, 1H)13C NMR(100MHz,CDCl3)δ:56.1,56.2,110.1,110.6,124.2, 129.7,138.6,142.3,149.7,154.5,187.8,193.0.MS:m/z 221[MH]+。
Embodiment 18
By method described in embodiment 1,1g (0.5mmol, 112mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product 2g (88mg, 92%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.39 (d, J=1.2Hz, 3H), 6.18 (dd, J1= 7.2Hz,J2=1.6Hz, 1H), 7.20-7.26 (m, 1H), 7.39-7.43 (m, 2H), 7.48 (dd, J1=6.0Hz, J2= 1.2Hz, 1H), 10.20 (d, J=7.2Hz, 1H)13C NMR(100MHz,CDCl3)δ:14.0,116.4(d,2JC-F= 22.6Hz),120.6(d,2JC-F=21.6Hz), 125.6 (d,4JC-F=3.1Hz), 130.5 (d,3JC-F=7.6Hz), 133.2, 137.4(d,3JC-F=5.6Hz), 152.5,162.7 (d,1JC-F=247.1Hz), 191.3,196.6 (d,4JC-F=2.0Hz) .MS:m/z 193[MH]+。
Embodiment 19
By method described in embodiment 1,1h (0.5mmol, 142mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow solid product 2h (120mg, 95%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.36 (d, J=1.6Hz, 3H), 6.12 (dd, J1= 7.6Hz,J2=1.2Hz, 1H), 7.52-7.58 (m, 4H), 10.17 (d, J=7.6Hz, 1H)13C NMR(100MHz,CDCl3) δ:14.1,128.8,131.2,132.0,132.8,134.1,152.6,191.3,196.8.MS:m/z 253[MH]+。
Embodiment 20
By method described in embodiment 1,1i (0.5mmol, 133mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow solid product 2i (111mg, 95%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.41 (d, J=1.6Hz, 3H), 3.89 (s, 3H), 3.92(s,3H),6.13(dd,J1=8.0Hz, J2=1.2Hz, 1H), 6.85 (d, J=8.4Hz, 1H), 7.35 (dd, J1= 8.0Hz,J2=2.0Hz, 1H), 7.41 (d, J=2.0Hz, 1H), 10.20 (d, J=7.6Hz, 1H)13C NMR(100MHz, CDCl3)δ:14.6,56.0,56.1,109.8,111.0,125.4,127.7,131.0,149.4,154.0,154.1,191.3, 196.1.MS:m/z 235[MH]+。
Embodiment 21
By method described in embodiment 1,1j (0.5mmol, 128mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product 2j (104mg, 93%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.55 (d, J=1.2Hz, 3H), 6.28 (dd, J1= 7.2Hz,J2=1.2Hz, 1H), 7.49-7.59 (m, 4H), 7.92 (m, 1H), 8.03 (d, J=8.0Hz, 1H), 8.12 (d, J= 8.8Hz, 1H), 10.32 (d, J=7.2Hz, 1H)13C NMR(100MHz,CDCl3)δ:13.1,124.3,125.2,126.8, 127.8,128.4,128.6,130.8,132.4,133.8,134.4,135.3,153.7,192.1,200.1.MS:m/z 225 [MH]+。
Embodiment 22
By method described in embodiment 1,1k (0.5mmol, 103mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=10:1) yellow liquid product 2k (69mg, 79%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.48 (d, J=1.6Hz, 3H), 6.31 (d, J= 7.2Hz,1H),7.55(dd,J1=4.4Hz, J2=1.6Hz, 2H), 8.82-8.83 (m, 2H), 10.33 (d, J=7.2Hz, 1H).13C NMR(100MHz,CDCl3)δ:13.3,119.9,122.4,134.9,142.5,150.8,191.3,197.1.MS: m/z 176[MH]+。
Embodiment 23
By method described in embodiment 1,1l (0.5mmol, 134mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product 2l (106mg, 90%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:6.33 (d, J=7.6Hz, 1H), 7.42-7.50 (m, 7H),7.58-7.61(m,1H),7.90(dd,J1=7.2Hz, J2=1.2Hz, 2H), 9.83 (d, J=7.2Hz, 1H)13C NMR(100MHz,CDCl3)δ:128.7,128.9,129.7,130.0,130.2,130.7,132.4,134.0,135.1, 157.2,192.7,195.3.MS:m/z 237[MH]+。
Embodiment 24
By method described in embodiment 1,1m (0.5mmol, 137mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow liquid product 2m (115mg, 95%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.06 (d, J=1.6Hz, 3H), 7.36 (d, J= 1.6Hz, 1H), 7.74 (d, J=8.8Hz, 2H), 8.02 (d, J=8.4Hz, 2H), 9.66 (s, 1H)13C NMR(150MHz, CDCl3)δ:11.6,123.6(d,1JC-F=271.2Hz), 126.5 (d,4JC-F=3.6Hz), 128.9 (d,3JC-F=5.9Hz), 130.9,135.2(d,2JC-F=32.7Hz), 139.9,149.4,190.8,194.3.MS:m/z 243[MH]+。
Embodiment 25
By method described in embodiment 1,1n (0.5mmol, 118mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow solid product 2n (94mg, 92%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.03 (s, 3H), 3.90 (s, 3H), 7.00 (d, J= 9.6Hz, 2H), 7.38 (d, J=1.2Hz, 1H), 7.95 (d, J=9.2Hz, 2H), 9.67 (s, 1H)13C NMR(100MHz, CDCl3)δ:11.3,55.5,127.0,130.0,131.0,141.0,147.0,164.3,190.5,194.7.MS:m/z 205 [MH]+。
Embodiment 26
By method described in embodiment 1,1o (0.5mmol, 128mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow solid product 2o (90mg, 80%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.11 (d, J=1.2Hz, 3H), 7.35 (d, J= 1.6Hz, 1H), 7.52-7.69 (m, 3H), 7.90-7.95 (m, 2H), 8.08 (d, J=8.4Hz, 1H), 8.78 (d, J= 8.8Hz,1H),9.69(s,1H).13C NMR(100MHz,CDCl3)δ:11.3,124.5,125.6,126.9,128.6, 128.8,130.0,130.3,134.0,134.2,134.8,143.1,147.4,194.9,195.1.MS:m/z 225[MH]+。
Embodiment 27
By method described in embodiment 1,1p (0.5mmol, 106mg) and dichloroethanes are added in the reaction flask of 25mL Then TEMPO (0.5mmol, 78mg) is added in (3mL).It is stirred to react 10 hours in 70 DEG C under oxygen (1atm) atmosphere, then 8mL saturated sodium chloride solution quenching reaction is added, is extracted with ethyl acetate (8mL × 3), merges organic phase, anhydrous sodium sulfate is dry It is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petrol ether/ethyl acetate=20:1) yellow solid product 2p (85mg, 94%) is obtained. The characterize data of the compound is as follows：1H NMR(400MHz,CDCl3)δ:2.17 (s, 3H), 7.20 (t, J=4.4Hz, 1H), 7.36 (s, 1H), 7.77 (d, J=4.0Hz, 1H), 7.81 (d, J=4.0Hz, 1H), 9.67 (s, 1H)13C NMR(100MHz, CDCl3)δ:11.3,128.6,132.8,135.5,138.3,145.0,148.8,183.3,194.7.MS:m/z 181[MH]+。
Embodiment above describes basic principles and main features of the invention and advantages.The technical staff of the industry should Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within In the scope of protection of the invention.

Claims (2)

  1. The synthetic method of (1. E) -4- oxo -2- butylene aldehyde compound, it is characterised in that：By (E)-4- nitro-2- butene-1- Ketone compounds 1 are dissolved in organic solvent, and oxidant is then added, and are made in air or oxygen atmosphere in 40-100 DEG C of reaction (E) -4- oxo -2- butylene aldehyde compound 2, the reaction equation in the synthetic method are：
    Wherein R1For 1- naphthalene, 4- pyridyl group, 2- thienyl, phenyl or substituted-phenyl, the substituent group on the substituted-phenyl phenyl ring is One of fluorine, chlorine, bromine, methyl, trifluoromethyl or methoxyl group are a variety of, and the position of substituent group is the ortho position on phenyl ring, meta position Or contraposition, R2For hydrogen, alkyl or phenyl, R3For hydrogen or alkyl, oxidant is tetramethyl piperidine nitrogen oxides, and organic solvent is first Benzene, acetonitrile, 1,4 dioxane or dichloroethanes.
  2. 2. the synthetic method of (E) -4- oxo -2- butylene aldehyde compound according to claim 1, it is characterised in that：Institute The ratio between amount for the substance that feeds intake of (the E)-4- nitro-2- butene-1 -one class compound 1 and oxidant stated is 1:0.5-2.
CN201610735202.XA 2016-08-26 2016-08-26 (E) synthetic method of -4- oxo -2- butylene aldehyde compound Active CN106431800B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610735202.XA CN106431800B (en) 2016-08-26 2016-08-26 (E) synthetic method of -4- oxo -2- butylene aldehyde compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610735202.XA CN106431800B (en) 2016-08-26 2016-08-26 (E) synthetic method of -4- oxo -2- butylene aldehyde compound

Publications (2)

Publication Number Publication Date
CN106431800A CN106431800A (en) 2017-02-22
CN106431800B true CN106431800B (en) 2018-11-23

Family

ID=58181869

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610735202.XA Active CN106431800B (en) 2016-08-26 2016-08-26 (E) synthetic method of -4- oxo -2- butylene aldehyde compound

Country Status (1)

Country Link
CN (1) CN106431800B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108863750B (en) * 2018-09-10 2021-02-19 河南师范大学 Synthetic method of 2-butene-1, 4-diketone compound
CN108976106B (en) * 2018-09-10 2021-02-19 河南师范大学 (E) Synthesis method of (E) -2-methylene-1, 4-butanedione compounds
CN114671746A (en) * 2022-03-31 2022-06-28 安徽中羰碳一工业技术有限责任公司 Synthesis method of 4-substituted cyclohexanone

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
First Exclusive Regioselective Fragmentation of Primary Ozonides Controlled by Remote Carbonyl Groups and a New Method for Determining the Regiochemistry of Carbonyl Oxide Formation;Hsien-Jen Wu等;《J. Org. Chem.》;19961231;第61卷;第3820-3828页 *
Titanium Silicalite 1（TS-1） Catalyzed Oxidative Transformations of Furan Derivatives with Hydrogen Peroxide;Joos Wahlen等;《Adv. Synth. Catal.》;20041231;第346卷;第333-338页 *

Also Published As

Publication number Publication date
CN106431800A (en) 2017-02-22

Similar Documents

Publication Publication Date Title
CN106431800B (en) (E) synthetic method of -4- oxo -2- butylene aldehyde compound
CN106631646B (en) The synthetic method of one kind (E) -4- oxo -2- butylene aldehyde compound
CN100391945C (en) S-(-)-indolyl-2-carboxylic acid synthesizing method
CN105801575B (en) A kind of synthetic method of imidazo [1,2-a] pyridine
CN107141207B (en) Synthetic method of 3 '-acyl-2, 4' -dihydroxy benzophenone compound
CN110511221A (en) A kind of synthetic method of polysubstituted aromatic ring simultaneously [1 ', 2 ': 4,5] imidazo [1,2-a] pyridine compounds and their
CN107501278A (en) A kind of synthetic method of the ketone of 5H furans 2 and piperidines
CN107629064B (en) A kind of synthetic method of Azacyclooctane and Furanones compound
CN107602452B (en) Synthetic method of 3-acyl pyridine compound
CN106892863B (en) The preparation method of vismodegib and its intermediate
CN107739332A (en) A kind of synthetic method of the formic ether compounds of pyridine 3
CN107827755A (en) A kind of synthetic method of ticagrelor midbody (1R, 2S) 2 (3,4 difluorophenyl) cyclopropylamine
CN107501277B (en) A kind of furanone and the synthetic method for hydrogenating azepines compound
CN110272403A (en) A method of carbamate of the synthesis containing chroman ring and trifluoromethyl
CN109369495A (en) A kind of synthetic method of pyrrolidones
KR101049475B1 (en) Aza-bicyclo [2.2.1] heptene derivative, preparation method thereof and preparation method of oseltamivir intermediate using the same
CN108516940A (en) A kind of synthetic method of 2- aminobenzophenones class compound
CN108516952A (en) A kind of synthetic method of the hexa-atomic nitrogen-containing hetero cyclics of 3- acyl groups
CN108586340A (en) A kind of synthetic method of 3- acyl groups hydrogenation azepines compound
CN103073520B (en) Method for synthesizing 2-phenyl benzothiazole and derivative thereof
CN102079720B (en) Method for preparing 1-benzylpiperidine-4-carboxaldehyde
CN106565604B (en) A kind of synthetic method of 5- nitro -8- amide groups quinolines
CN108503572A (en) A kind of synthetic method of 3- acyl pyrrolines class compound
CN106565625B (en) A kind of antiplatelet reduces the preparation method of disease new drug Lusutrombopag intermediates
CN110294758A (en) 2- replaces 5,6- dihydro-pyrazolo [5,1- α] isoquinolin, derivative and its synthetic method

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant