CN107746391A - Synthetic method of isoxazoline compound - Google Patents
Synthetic method of isoxazoline compound Download PDFInfo
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- CN107746391A CN107746391A CN201710990710.7A CN201710990710A CN107746391A CN 107746391 A CN107746391 A CN 107746391A CN 201710990710 A CN201710990710 A CN 201710990710A CN 107746391 A CN107746391 A CN 107746391A
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- -1 isoxazoline compound Chemical class 0.000 title claims description 17
- 238000010189 synthetic method Methods 0.000 title claims description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 46
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
- 239000000758 substrate Substances 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 claims description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 11
- 239000000741 silica gel Substances 0.000 claims description 11
- 229910002027 silica gel Inorganic materials 0.000 claims description 11
- 238000001514 detection method Methods 0.000 claims description 10
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 238000012360 testing method Methods 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- 229940125904 compound 1 Drugs 0.000 claims 2
- 229940125782 compound 2 Drugs 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 11
- 239000002253 acid Substances 0.000 abstract description 6
- 150000002148 esters Chemical class 0.000 abstract description 6
- 239000002879 Lewis base Substances 0.000 abstract description 4
- 150000007527 lewis bases Chemical class 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 150000002547 isoxazolines Chemical class 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 229930014626 natural product Natural products 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 abstract 1
- 239000007810 chemical reaction solvent Substances 0.000 abstract 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
- 150000002923 oximes Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 238000005660 chlorination reaction Methods 0.000 description 4
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- 150000001361 allenes Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- DFOQDORWNLHNCK-ALCCZGGFSA-O CC(C)=C/C=[NH+]\C Chemical compound CC(C)=C/C=[NH+]\C DFOQDORWNLHNCK-ALCCZGGFSA-O 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses a method for synthesizing isoxazoline compounds, which comprises the step of reacting in a reaction solvent by taking allenoic acid ester and aldehyde oxime chloride as reaction raw materials and Lewis base as a catalyst to obtain the isoxazoline compounds. The method has the advantages of mild reaction conditions, easily obtained and cheap raw materials, simple reaction operation and higher yield, provides a key framework structure for the synthesis of a plurality of natural products and medicines, and can be widely applied to industrial mass production.
Description
Technical field
Present invention relates particularly to a kind of synthetic method for preparing isoxazoles compound, and belonging to organic compound technique should
Use technical field.
Background technology
Isoxazoles compound is a kind of extremely important pharmaceutical-chemical intermediate, has very high application value.Very
Drug and bioactive molecule all have the skeleton of isoxazoline.Synthesis isoxazoles compound conventional method be mainly
Prepared by the method for metal catalytic.But in the method, the use of heavy metal can cause seriously to pollute to environment, make this side
The application of method is restricted.
The content of the invention
The present invention overcomes the disadvantages described above of prior art, innovatively proposes a kind of green, simple efficiently system first
The new method of standby loop coil isoxazoles compound, is catalyst by using lewis base, can efficiently realize reaction
Conversion.As shown in above formula (I), the present invention is utilized to join olefin(e) acid ester and chlorination aldoxime as reaction raw materials, using lewis base to urge
Agent, reacted in reaction dissolvent, synthesizing spiro isoxazoles compound.
In the present invention, R is alkyl, aromatic radical or substituted aromatic ring and heterocycle, all kinds of side chains.
In the present invention, the usage ratio of the initiation material connection olefin(e) acid ester and chlorination aldoxime is 1:3.Preferably, Liang Zheyong
Amount ratio is 1:5.
In the present invention, the catalyst is Δ ABCO；The dosage of the catalyst is 1-100%.The use of the catalyst
Measure the 1-100mol% for joining olefin(e) acid ester for raw material.Preferably, the catalyst amount is 20mol%.
In the present invention, the reaction dissolvent is toluene, chloroform, tetrahydrofuran, Δ MA, 1,2- dichloroethanes, THF or second
Nitrile.The reaction dissolvent can also be chlorobenzene, Isosorbide-5-Nitrae-dioxane, Δ MF, Δ MSO more than including but is not limited to.
In the present invention, the synthetic reaction is carried out at a temperature of 20-80 DEG C.Preferably, it is to be reacted at 50 DEG C.
Specifically, synthetic reaction of the present invention is in reaction bulb A, by allene acid esters (substrate 1, X mmol) and chlorination aldehyde
Oxime (substrate 2, Y mmol) is dissolved in Z mL reaction dissolvents, at room temperature, adds triethylamine (W mmol) and Δ ABCO (Z
mmol).12 hours are reacted in reaction at 20-80 DEG C.Reaction process is detected with TLC.After completion of the reaction, silica gel, rotation are directly added
Dry chromatography, isolated target product 3.
The advantages of synthetic reaction of the present invention, includes：Each raw material is very simple used in synthetic method of the present invention, is work
Industry commodity, simple and easy to get, wide material sources, and performance is highly stable, it is not necessary to special preservation condition.It is each used in the present invention
Kind catalyst is also all conventional commercial reagents, highly stable.Traditional method one of synthesizing spiro isoxazoline compound
As be to be realized using the method for metal catalytic.But the use of heavy metal can cause seriously to pollute to environment, to industrial metaplasia
Production causes very big limitation.The present invention is using allene acid esters and chlorination aldoxime simple and easy to get as reaction raw materials, in lewis base
Under effect, reaction obtains loop coil isoxazoles compound.Operation is fairly simple, and reaction condition is gentle, and yield is higher, fits
Close large-scale industrial production.The loop coil isoxazoles compound that the present invention synthesizes is many natural products and active medicine point
The core skeleton of son, the reaction scheme of innovative design of the present invention provide a generally applicable preparation to synthesize this kind of compound
Method.
Embodiment
With reference to specific examples below, the present invention is described in further detail, and of the invention protects content not limit to
In following examples.Under the spirit and scope without departing substantially from inventive concept, those skilled in the art it is conceivable that change and excellent
Point is all included in the present invention, and using appended claims as protection domain.Implement the present invention process, condition,
Reagent, experimental method etc., it is the universal knowledege and common knowledge of this area in addition to the following content specially referred to, this hair
It is bright that content is not particularly limited.Data given by following examples include concrete operations and reaction condition and product.Product is pure
Degree is identified by nuclear magnetic resonance.
Embodiment 1
In 25 mL test tube reactor, with nitrogen exchange of air 3 times.By substrate 1a (0.1 mmol, 11.2 mg), substrate
2b (0.3 mmol, 46.5 mg), triethylamine (0.3 mmol, 30.3 mg), Δ ABCO (0.02 mmol, 2.24 mg)
Reaction tube is weighed into successively, and nitrogen is changed in evacuation, and adds dichloromethane (0.3 mL) under nitrogen atmosphere, and it is small to react 24 at room temperature
When.After TLC detection reactions terminate, directly add silica gel, be spin-dried for column chromatography, obtain yellow oily 3aa (96 %).1H NMR (CΔ
Cl3, 500 MHz): δ (ppm) 7.81-7.79 (m, 2H), 7.45-7.44 (m, 3H), 6.60 (s, 1H),
4.24 (q, J = 10.0 Hz, 2H), 3.87 (s, 2H), 1.30 (t, J = 10.0 Hz, 3H). 13C NMR (C
ΔCl3, 125 MHz): δ (ppm) 167.6, 165.7, 162.6, 130.0, 129.0, 128.9, 126.8,
101.4, 61.7, 32.9, 14.1. HRMS (ESI): exact mass calculateδ for M+ (C13H14NO3)
requires m/z 232.0974, founδ m/z 232.0978.
Embodiment 2
In 25 mL test tube reactor, with nitrogen exchange of air 3 times.By substrate 1a (0.1 mmol, 11.2 mg), substrate
2c (0.3 mmol, 46.5 mg), triethylamine (0.3 mmol, 30.3 mg), Δ ABCO (0.02 mmol, 2.24 mg)
Reaction tube is weighed into successively, and nitrogen is changed in evacuation, and adds dichloromethane (0.3 mL) under nitrogen atmosphere, reacts 24 at room temperature
Hour.After TLC detection reactions terminate, directly add silica gel, be spin-dried for column chromatography, obtain white solid 3ab (87 %).1H NMR (CΔ
Cl3, 500 MHz): δ (ppm) 7.68-7.67 (m, 2H), 7.59-7.58 (m, 2H), 6.58 (s, 1H),
4.24 (q, J= 10.0 Hz, 2H), 3.87 (s, 2H), 1.31 (t, J = 10.0 Hz, 3H). 13C NMR (C
ΔCl3, 125 MHz): δ (ppm) 167.6, 166.2, 161.8, 132.2, 128.4, 128.0, 124.4,
101.4, 61.9, 32.9, 14.2. HRMS (ESI): exact mass calculateδ for M+ (C13H13BrNO3)
requires m/z 310.0079, founδ m/z 310.0082.
Embodiment 3
In 25 mL test tube reactor, with nitrogen exchange of air 3 times.By substrate 1a (0.1 mmol, 11.2 mg), substrate
2 δ (0.3 mmol, 46.5 mg), triethylamine (0.3 mmol, 30.3 mg), Δ ABCO (0.02 mmol, 2.24 mg)
Reaction tube is weighed into successively, and nitrogen is changed in evacuation, and adds dichloromethane (0.3 mL) under nitrogen atmosphere, reacts 24 at room temperature
Hour.After TLC detection reactions terminate, directly add silica gel, be spin-dried for column chromatography, obtain yellow oily 3ac (96 %).1H NMR (C
ΔCl3, 500 MHz): δ (ppm) 7.58-7.57 (m, 1H), 7.53-7.51 (m, 1H), 7.44-7.40 (m,
1H), 7.15-7.12 (m, 1H), 6.59 (s, 1H), 4.24 (q, J = 10.0 Hz, 2H), 3.87 (s,
2H), 1.30 (t, J = 10.0 Hz, 3H). 13C NMR (CΔCl3, 125 MHz): δ (ppm) 167.5,
166.2, 163.0 (J = 820.0 Hz), 161.7, 130.1 (J = 25.0 Hz), 130.6 (J = 25.0 Hz),
122.6, 117.0 (J = 65.0 Hz), 113.8 (J = 80.0 Hz), 101.5, 61.9, 32.9, 14.1.
HRMS (ESI): exact mass calculateδ for M+ (C13H13FNO3) requires m/z 250.0879,
founδ m/z 250.0885.
Embodiment 4
In 25 mL test tube reactor, with nitrogen exchange of air 3 times.By substrate 1a (0.1 mmol, 11.2 mg), substrate
2e (0.3 mmol, 46.5 mg), triethylamine (0.3 mmol, 30.3 mg), Δ ABCO (0.02 mmol, 2.24 mg)
Reaction tube is weighed into successively, and nitrogen is changed in evacuation, and adds dichloromethane (0.3 mL) under nitrogen atmosphere, reacts 24 at room temperature
Hour.After TLC detection reactions terminate, directly add silica gel, be spin-dried for column chromatography, obtain yellow oily 3a δ (80 %).1H NMR (C
ΔCl3, 500 MHz): δ (ppm) 7.64 (s, 1H), 7.59-7.58 (m, 1H), 7.35-7.33 (m, 1H),
7.26-7.25 (m, 1H), 6.59 (s, 1H), 4.24 (q, J = 10.0 Hz, 2H), 3.87 (s, 2H),
2.41 (s, 3H), 1.30 (t, J = 10.0 Hz, 3H). 13C NMR (CΔCl3, 125 MHz): δ (ppm)
167.7, 165.7, 162.9, 138.7, 131.0, 130.8, 128.9, 127.5, 124.1, 101.6, 61.9,
33.0, 21.5, 14.2. HRMS (ESI): exact mass calculateδ for M+ (C14H16NO3) requires
m/z 246.1130, founδ m/z 246.1134.
Embodiment 5
In 25 mL test tube reactor, with nitrogen exchange of air 3 times.By substrate 1a (0.1 mmol, 11.2 mg), substrate
2f (0.3mmol, 46.5 mg), triethylamine (0.3 mmol, 30.3 mg), Δ ABCO (0.02 mmol, 2.24 mg)
Reaction tube is weighed into successively, and nitrogen is changed in evacuation, and adds dichloromethane (0.3 mL) under nitrogen atmosphere, reacts 24 at room temperature
Hour.After TLC detection reactions terminate, directly add silica gel, be spin-dried for column chromatography, obtain yellow oily 3ae (92 %).1H NMR (C
ΔCl3, 500 MHz): δ (ppm) 7.98-7.96 (m, 1H), 7.43-7.41 (m, 1H), 7.24-7.23 (m,
1H), 7.19-7.15 (m, 1H), 6.72 (s, 1H), 4.24 (q, J = 10.0 Hz, 2H), 3.88 (s,
2H), 1.30 (t, J = 10.0 Hz, 3H). 13C NMR (CΔCl3, 125 MHz): δ (ppm) 167.6,
165.7, 160.4 (J = 835.0 Hz), 158.2, 131.7 (J = 30.0 Hz), 129.2, 124.7 (J =
15.0 Hz), 117.1 (J = 40.0 Hz), 116.4 (J = 75.0 Hz), 104.1 (J = 30.0 Hz),
61.9, 33.0, 14.2. HRMS (ESI): exact mass calculateδ for M+ (C13H13FNO3)
requires m/z 250.0879, founδ m/z 250.0884.
Embodiment 6
In 25 mL test tube reactor, with nitrogen exchange of air 3 times.By substrate 1a (0.1 mmol, 11.2 mg), substrate
2g (0.3 mmol, 46.5 mg), triethylamine (0.3 mmol, 30.3 mg), Δ ABCO (0.02 mmol, 2.24 mg)
Reaction tube is weighed into successively, and nitrogen is changed in evacuation, and adds dichloromethane (0.3 mL) under nitrogen atmosphere, reacts 24 at room temperature
Hour.After TLC detection reactions terminate, directly add silica gel, be spin-dried for column chromatography, obtain yellow oily 3af (84 %).1H NMR (C
ΔCl3, 500 MHz): δ (ppm) 7.69-7.67 (m, 1H), 7.65-7.63 (m, 1H), 7.39-7.38 (m,
1H), 7.32-7.30 (m, 1H), 6.72 (s, 1H), 4.24 (q, J = 10.0 Hz, 2H), 3.90 (s,
2H), 1.31 (t, J = 10.0 Hz, 3H). 13C NMR (CΔCl3, 125 MHz): δ (ppm) 167.5,
164.8, 162.6, 133.6, 131.3, 131.0, 130.4, 127.6, 122.2, 104.8, 61.7, 32.9,
14.1. HRMS (ESI): exact mass calculateδ for M+ (C13H13BrNO3) requires m/z
310.0079, founδ m/z 310.0085.
Embodiment 7
In 25 mL test tube reactor, with nitrogen exchange of air 3 times.By substrate 1a (0.1 mmol, 11.2 mg), substrate
2h (0.3mmol, 46.5 mg), triethylamine (0.3 mmol, 30.3 mg), Δ ABCO (0.02 mmol, 2.24 mg)
Reaction tube is weighed into successively, and nitrogen is changed in evacuation, and adds dichloromethane (0.3 mL) under nitrogen atmosphere, reacts 24 at room temperature
Hour.After TLC detection reactions terminate, directly add silica gel, be spin-dried for column chromatography, obtain yellow oily 3ag (92 %).1H NMR (C
ΔCl3, 500 MHz): δ (ppm) 7.74-7.73 (m, 1H), 7.49-7.48 (m, 1H), 7.40-7.35 (m,
2H), 6.75 (s, 1H), 4.24 (q, J = 10.0 Hz, 2H), 3.89 (s, 2H), 1.30 (t, J = 10.0
Hz, 3H). 13C NMR (CΔCl3, 125 MHz): δ (ppm) 167.5, 165.0, 161.2, 133.0, 131.0,
130.8, 130.4, 128.3, 127.1, 104.7, 61.8, 32.9, 14.1. HRMS (ESI): exact mass
calculateδ for M+ (C13H13ClNO3) requires m/z 266.0584, founδ m/z 266.0589.
Embodiment 8
In 25 mL test tube reactor, with nitrogen exchange of air 3 times.By substrate 1a (0.1 mmol, 11.2 mg), substrate
2i (0.3mmol, 46.5 mg), triethylamine (0.3 mmol, 30.3 mg), Δ ABCO (0.02 mmol, 2.24 mg)
Reaction tube is weighed into successively, and nitrogen is changed in evacuation, and adds dichloromethane (0.3 mL) under nitrogen atmosphere, reacts 24 at room temperature
Hour.After TLC detection reactions terminate, directly add silica gel, be spin-dried for column chromatography, obtain yellow oily 3ah (85 %).1H NMR (C
ΔCl3, 500 MHz): δ (ppm) 7.40-7.39 (m, 1H), 7.11-7.07 (m, 2H), 6.44 (s, 1H),
4.24 (q, J = 10.0 Hz, 2H), 3.87 (s, 2H), 2.45 (s, 3H), 2.36 (s, 3H), 1.30 (t,J = 10.0 Hz, 3H). 13C NMR (CΔCl3, 125 MHz): δ (ppm) 167.8, 164.7, 163.3,
139.5, 136.8, 132.0, 131.9, 129.4, 126.8, 104.1, 61.8, 32.9, 21.3, 21.1,
14.2. HRMS (ESI): exact mass calculateδ for M+ (C15H18NO3) requires m/z
260.1287, founδ m/z 260.1290.
Embodiment 9
In 25 mL test tube reactor, with nitrogen exchange of air 3 times.By substrate 1a (0.1 mmol, 11.2 mg), substrate
2j (0.3 mmol, 46.5 mg), triethylamine (0.3 mmol, 30.3 mg), Δ ABCO (0.02 mmol, 2.24 mg)
Reaction tube is weighed into successively, and nitrogen is changed in evacuation, and adds dichloromethane (0.3 mL) under nitrogen atmosphere, reacts 24 at room temperature
Hour.After TLC detection reactions terminate, directly add silica gel, be spin-dried for column chromatography, obtain yellow oily 3ai (71 %).1H NMR (C
ΔCl3, 500 MHz): δ (ppm) 8.24 (s, 1H), 7.96-7.90 (m, 4H), 7.54-7.52 (m, 2H),
6.75 (s, 1H), 4.26 (q, J = 10.0 Hz, 2H), 3.91 (s, 2H), 1.32 (t, J = 10.0 Hz,
3H). 13C NMR (CΔCl3, 125 MHz): δ (ppm) 167.7, 165.9, 162.8, 134.1, 133.3,
128.9, 128.6, 127.9, 127.1, 126.8, 126.7, 126.5, 124.0, 101.7, 61.9, 33.0,
14.2. HRMS (ESI): exact mass calculateδ for M+ (C17H16NO3) requires m/z
282.1230, founδ m/z 282.1232。
Claims (5)
1. a kind of synthetic method of isoxazoles compound, it is characterised in that with compound 1 be reaction raw materials, with Louis
Alkali is catalyst, is reacted under certain temperature in reaction dissolvent and obtains isoxazoles compound；Wherein, the temperature is 20-
80℃；Shown in course of reaction such as formula (I)；
Wherein R is alkyl, aromatic radical or heterocycle.
2. the synthetic method of isoxazoles compound as claimed in claim 1, it is characterised in that the catalyst is Δ
ABCO；The dosage of the catalyst is 1-100%.
3. the synthetic method of isoxazoles compound as claimed in claim 1, it is characterised in that the reaction dissolvent is first
Benzene, chloroform, tetrahydrofuran, Δ MA, 1,2- dichloroethanes, THF, chlorobenzene, Isosorbide-5-Nitrae-dioxane, Δ MF, Δ MSO or acetonitrile.
4. the synthetic method of isoxazoles compound as claimed in claim 1, it is characterised in that the compound 1 and change
The ratio of compound 2 is 1:3.
5. a kind of synthetic method of isoxazoles compound, course of reaction is as shown in formulas below；
In 25 mL test tube reactor, with nitrogen exchange of air 3 times；By 0.1mmol substrates 1a, 0.3 mmol substrates 2a,
0.3 mmol triethylamines and 0.02mmol Δs ABCO are weighed into reaction tube successively, and nitrogen is changed in evacuation, and adds under nitrogen atmosphere
0.15 mL chloroforms；Reaction system is reacted at room temperature 24 hours；After TCL detection reactions terminate, directly add silica gel, rotation
Dry chromatography, obtain 3aa.
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2017
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| Title |
|---|
| K. BAST, ET AL: "Additionen des Benzonitriloxides an olefinische und acetylenische Dipolarophile", 《CHEM BER》 * |
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