CN110483449A - A kind of preparation method of gamma lactone derivative - Google Patents
A kind of preparation method of gamma lactone derivative Download PDFInfo
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
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Abstract
The invention discloses a kind of preparation methods of gamma lactone derivative, the following steps are included: using aromatic derivant carboxylate, alkene derivatives and alcohol as reaction substrate, using halide as catalyst, in the presence of oxidant, 60-100 DEG C of reaction temperature, reaction time 8-16 hour prepares gamma lactone derivative；The dosage of the alkene is 4~6 times of the amount of the substance of the aromatic derivant carboxylate；The dosage of the alcohol is 40~60 times of the amount of the substance of the aromatic derivant carboxylate；The dosage of the catalyst is the 40~60% of the amount of the substance of the aromatic derivant carboxylate；The dosage of the oxidant is 4~6 times of the amount of the substance of the aromatic derivant carboxylate.The present invention is used using aromatic derivant carboxylate, alkene derivatives and alcohol as reaction substrate, and using halide as catalyst preparation gamma lactone derivative, mild condition avoids the use of transition metal without the condition of anaerobic, reduces the harm to environment.
Description
Technical field
The present invention relates to a kind of lactone compound more particularly to a kind of preparation methods of gamma lactone derivative.
Background technique
Gamma lactone is a kind of very important structural unit, is widely present in many active natural with important biomolecule
In product and drug molecule, with significant application value and various pharmacological action in pharmaceutical chemistry, if any stronger anti-
The effects of cancer, antibacterial, in addition in synthetic intermediate and food additives are also often seen.Therefore development efficiently synthesizes γ-
The new method of lactone derivatives is very active one of research field.It is needed in γ-lactones derivative method currently, preparing
Using noble metal, not only price costly, be more toxic, and synthetic route there is also the synthesis of raw material complicated, reaction item
Harsh, cumbersome, substrate use scope the is narrow disadvantage of part.Such as:
(1) Huanfeng Jiang etc. is using high alkenyl 01 derivatives in palladium acetate, copper chloride and ligand united effect
Under, nucleophilicity palladium intermediate, which is generated, with the hydroxyl in high alkenyl alcohol is obtained then to alkene nucleophilic attack with preferable yield
Gamma lactone derivative, but need that the transition metal such as palladium are added in reaction system.(referring to: Zheng, M.；Chen,P.；
Huang,L.；Wu,W.；Jiang,H.Org.Lett.2017,19,5756-5759).
(2) Longwu Ye etc. reports gold and is catalyzed high alkenyl 01 derivatives series connection ring isomerism/oxidation reaction, and the reaction is first
Connection alkene gold intermediate is first undergone, gold card guest is then generated by the hydroxyl capture of intramolecular, most gamma lactone is obtained through oxidation afterwards and derives
Object, but the use of Au catalyst greatly limits its application in industry generates.(referring to: Shu, C.；Liu,M-q.；
Sun,Y-Z.；Ye,L-W.Org.Lett.2012,14,4958–4961).
Therefore find that a kind of raw material sources are simple, reactivity is higher, preparation at low cost, safe and environment-friendly, good operability
Method is necessary to be effectively synthesized gamma lactone derivative.
Summary of the invention
Goal of the invention of the invention is to provide a kind of preparation method of gamma lactone derivative, so that reaction is in mild item
While reaction under part, the use of catalyst expensive or that toxicity is high is avoided.
The technical solution of the present invention is as follows:
A kind of preparation method of gamma lactone derivative, comprising the following steps: derivative with aromatic derivant carboxylate, alkene
Object and alcohol are reaction substrate, using halide as catalyst, in the presence of oxidant, 60-100 DEG C of reaction temperature, it is seasonable between 8-
Gamma lactone derivative is prepared within 16 hours；
Wherein: the chemical structural formula of the aromatic derivant carboxylate isR in formula1Be selected from: naphthalene, heterocycle or
Monosubstituted arylR2It is selected from: hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, phenyl, trifluoromethyl or nitro；It is described
Heterocycle is selected from thienyl or pyridyl group；The chemical structural formula of the alkene derivatives isThe 01 derivatives
Chemical structural formula isThe halide is selected from: sodium iodide, iodine
Change one of potassium, tetrabutylammonium iodide or tetrabutylammonium chloride；The oxidant is selected from: tert-butyl hydroperoxide, mistake
Aoxidize one of di-t-butyl, hydrogen peroxide or potassium peroxydisulfate complex salt；The dosage of the alkene is that the aromatic carboxylic acid spreads out
4~6 times of the amount of the substance of biology；The dosage of the alcohol is the 40~60 of the amount of the substance of the aromatic derivant carboxylate
Times；The dosage of the catalyst is the 40~60% of the amount of the substance of the aromatic derivant carboxylate；The use of the oxidant
Amount is 4~6 times of the amount of the substance of the aromatic derivant carboxylate.
Reaction formula of the invention are as follows:
Wherein R1For aryl, R4For alkyl.
After the reaction was completed, with saturated sodium sulfite quenching reaction, be extracted with ethyl acetate, saturated common salt water washing three times,
Anhydrous sodium sulfate dries organic layer, and then carrying out simple column chromatography with the mixed solvent of ethyl acetate and petroleum ether can obtain finally
Product.
Preferably, the dosage of the alkene is 5 times of the amount of the substance of the aromatic derivant carboxylate.
Preferably, the dosage of the alcohol is 50 times of the amount of the substance of the aromatic derivant carboxylate.
Preferably, the dosage of the catalyst is the 50% of the amount of the substance of the aromatic derivant carboxylate.
Preferably, the dosage of the oxidant is 5 times of the amount of the substance of the aromatic derivant carboxylate.
Preferably, the reaction temperature is 80 DEG C；Reaction time 12 hours.
Preferably, the reaction carries out in a solvent, and the solvent is acetonitrile, tetrahydrofuran, ethyl acetate, dioxane
Or N,N-dimethylformamide.
The invention has the benefit that
In the method for preparing gamma lactone class compound of the prior art, transition-metal catalyst, transition gold are generally required
Catalyst containing precious metal elements such as gold, palladiums in category not only high production cost, and complex disposal process thereafter, environmental pollution are tight
Weight；And with the production method containing other transition metal elements as catalyst, it can be because of transition-metal catalyst in air
It is easily oxidized into other valence states and then makes catalyst inactivation, cause the efficiency entirely reacted to substantially reduce, therefore producing
The environment using anaerobic is needed in the process, and working condition is harsh.And with aromatic derivant carboxylate, alkene derivatives in the present invention
With alcohol as reaction substrate, using halide as catalyst preparation gamma lactone derivative, which can be steady in oxygen or air
It is fixed to exist, it is not influenced by the oxygen in air, therefore can be produced under conditions of aerobic, reaction condition is mild, reduces
Working condition and production cost improve production efficiency, while avoiding the use of noble metal or transition metal, reduce to ring
The harm in border and the cumbersome process of post-processing.
Specific embodiment
It elaborates With reference to embodiment to the present invention.
Embodiment 1:
Reaction equation in the present embodiment are as follows:
Compound 1a (1mmol), compound 2a (5mmol), 3a (50mmol), sodium iodide are sequentially loaded into reaction flask
(abbreviation NaI) (0.50mmol), tert-butyl hydroperoxide (abbreviation TBHP) (5mmol) and solvent ethyl acetate (abbreviation EtOAc)
5mL, with saturated sodium sulfite quenching reaction, uses ethyl acetate after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing
Extract (20mL × 3), saturated common salt water washing three times, the dry organic layer of anhydrous sodium sulfate can be obtained by simple column chromatography
Product 4a, yield 54%.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.47
(d, J=8.3Hz, 2H), 5.81 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,8.7Hz, 1H), 2.26-2.14 (m,
1H),1.56(s,3H),1.49(s,3H),1.33(s,9H)；13C NMR(101MHz,CDCl3)δ171.92,165.04,
157.14,129.61,125.74,125.23,82.08,69.28,40.89,34.87,30.79,28.77,27.61；HRMS
(ESI-TOF):Anal.Calcd.For C17H22O4:219.1591,Found:219.1589(M+H+)。
Embodiment 2:
Reaction equation in the present embodiment are as follows:
Compound 1a (1mmol), compound 2a (5mmol), 3a (50mmol), potassium iodide are sequentially loaded into reaction flask
(abbreviation KI) (0.50mmol), TBHP (5mmol) and solvent acetonitrile (abbreviation CH3CN) 5mL, then the system is in 80 DEG C of items of tube sealing
After heating 12 hours under part, with saturated sodium sulfite quenching reaction, (20mL × 3), saturated common salt washing is extracted with ethyl acetate
It washs three times, the dry organic layer of anhydrous sodium sulfate can obtain product 4a, yield 67% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.47
(d, J=8.3Hz, 2H), 5.81 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,8.7Hz, 1H), 2.26-2.14 (m,
1H),1.56(s,3H),1.49(s,3H),1.33(s,9H)；13C NMR(101MHz,CDCl3)δ171.92,165.04,
157.14,129.61,125.74,125.23,82.08,69.28,40.89,34.87,30.79,28.77,27.61；HRMS
(ESI-TOF):Anal.Calcd.For C17H22O4:219.1591,Found:219.1589(M+H+)。
Embodiment 3:
Reaction equation in the present embodiment are as follows:
Compound 1a (1mmol), compound 2a (5mmol), 3a (50mmol), tetra-n-butyl are sequentially loaded into reaction flask
Ammonium chloride (abbreviation TBAC) (0.50mmol), TBHP (5mmol) and solvents tetrahydrofurane (abbreviation THF) 5mL, then the system exists
After being heated 12 hours under the conditions of 80 DEG C of tube sealing, with saturated sodium sulfite quenching reaction, (20mL × 3) is extracted with ethyl acetate, satisfy
Three times with brine It, the dry organic layer of anhydrous sodium sulfate can obtain product 4a by simple column chromatography, and yield is
33%.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.47
(d, J=8.3Hz, 2H), 5.81 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,8.7Hz, 1H), 2.26-2.14 (m,
1H),1.56(s,3H),1.49(s,3H),1.33(s,9H)；13C NMR(101MHz,CDCl3)δ171.92,165.04,
157.14,129.61,125.74,125.23,82.08,69.28,40.89,34.87,30.79,28.77,27.61；HRMS
(ESI-TOF):Anal.Calcd.For C17H22O4:219.1591,Found:219.1589(M+H+)。
Embodiment 4:
Reaction equation in the present embodiment are as follows:
Compound 1a (1mmol), compound 2a (5mmol), 3a (50mmol), tetra-n-butyl are sequentially loaded into reaction flask
Ammonium iodide (abbreviation TBAI) (0.50mmol), di-t-butyl peroxide (abbreviation DTBP) (5mmol) and solvent 1,4- dioxane
(abbreviation Dioxane) 5mL is quenched instead after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing with saturated sodium sulfite
It answers, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, the dry organic layer of anhydrous sodium sulfate, by simple
Column chromatography can obtain product 4a, yield 76%.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.47
(d, J=8.3Hz, 2H), 5.81 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,8.7Hz, 1H), 2.26-2.14 (m,
1H),1.56(s,3H),1.49(s,3H),1.33(s,9H)；13C NMR(101MHz,CDCl3)δ171.92,165.04,
157.14,129.61,125.74,125.23,82.08,69.28,40.89,34.87,30.79,28.77,27.61；HRMS
(ESI-TOF):Anal.Calcd.For C17H22O4:219.1591,Found:219.1589(M+H+)。
Embodiment 5:
Reaction equation in the present embodiment are as follows:
Compound 1a (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI are sequentially loaded into reaction flask
(0.50mmol), hydrogen peroxide (abbreviation H2O2) (5mmol) and solvent n,N-Dimethylformamide (abbreviation DMF) 5mL, the then body
After being heated 12 hours under the conditions of tying up to 80 DEG C of tube sealing, with saturated sodium sulfite quenching reaction, be extracted with ethyl acetate (20mL ×
3), three times, the dry organic layer of anhydrous sodium sulfate can obtain product 4a, yield by simple column chromatography to saturated common salt water washing
It is 43%.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.47
(d, J=8.3Hz, 2H), 5.81 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,8.7Hz, 1H), 2.26-2.14 (m,
1H),1.56(s,3H),1.49(s,3H),1.33(s,9H)；13C NMR(101MHz,CDCl3)δ171.92,165.04,
157.14,129.61,125.74,125.23,82.08,69.28,40.89,34.87,30.79,28.77,27.61；HRMS
(ESI-TOF):Anal.Calcd.For C17H22O4:219.1591,Found:219.1589(M+H+)。
Embodiment 6:
Reaction equation in the present embodiment are as follows:
Compound 1a (1mmol), compound 2a (4mmol), 3a (40mmol), tetra-n-butyl are sequentially loaded into reaction flask
Ammonium iodide (abbreviation TBAI) (0.50mmol), potassium peroxydisulfate complex salt (i.e. K2S2O8) (5mmol) and solvent ethyl acetate 5mL, so
After the system heats 12 hours under the conditions of 80 DEG C of tube sealing afterwards, with saturated sodium sulfite quenching reaction, it is extracted with ethyl acetate
Three times, the dry organic layer of anhydrous sodium sulfate can obtain product by simple column chromatography for (20mL × 3), saturated common salt water washing
4a, yield 35%.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.47
(d, J=8.3Hz, 2H), 5.81 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,8.7Hz, 1H), 2.26-2.14 (m,
1H),1.56(s,3H),1.49(s,3H),1.33(s,9H)；13C NMR(101MHz,CDCl3)δ171.92,165.04,
157.14,129.61,125.74,125.23,82.08,69.28,40.89,34.87,30.79,28.77,27.61；HRMS
(ESI-TOF):Anal.Calcd.For C17H22O4:219.1591,Found:219.1589(M+H+)。
Embodiment 7:
Reaction equation in the present embodiment are as follows:
Compound 1a (1mmol), compound 2a (6mmol), 3a (60mmol), tetra-n-butyl are sequentially loaded into reaction flask
Ammonium iodide (abbreviation TBAI) (0.50mmol), TBHP (5mmol) and solvent ethyl acetate 5mL, then the system is at 80 DEG C of tube sealing
Under the conditions of heat 12 hours after, with saturated sodium sulfite quenching reaction, (20mL × 3), saturated salt solution are extracted with ethyl acetate
Three times, the dry organic layer of anhydrous sodium sulfate can obtain product 4a, yield 88% by simple column chromatography for washing.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.47
(d, J=8.3Hz, 2H), 5.81 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,8.7Hz, 1H), 2.26-2.14 (m,
1H),1.56(s,3H),1.49(s,3H),1.33(s,9H)；13C NMR(101MHz,CDCl3)δ171.92,165.04,
157.14,129.61,125.74,125.23,82.08,69.28,40.89,34.87,30.79,28.77,27.61；HRMS
(ESI-TOF):Anal.Calcd.For C17H22O4:219.1591,Found:219.1589(M+H+)。
Embodiment 8:
Reaction equation in the present embodiment are as follows:
Compound 1a (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI are sequentially loaded into reaction flask
(0.40mmol), TBHP (4mmol) and solvent ethyl acetate 5mL, then the system heats 8 hours under the conditions of 60 DEG C of tube sealing
Afterwards, with saturated sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous slufuric acid
Sodium dries organic layer, can obtain product 4a, yield 72% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.47
(d, J=8.3Hz, 2H), 5.81 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,8.7Hz, 1H), 2.26-2.14 (m,
1H),1.56(s,3H),1.49(s,3H),1.33(s,9H)；13C NMR(101MHz,CDCl3)δ171.92,165.04,
157.14,129.61,125.74,125.23,82.08,69.28,40.89,34.87,30.79,28.77,27.61；HRMS
(ESI-TOF):Anal.Calcd.For C17H22O4:219.1591,Found:219.1589(M+H+)。
Embodiment 9:
Reaction equation in the present embodiment are as follows:
Compound 1a (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI are sequentially loaded into reaction flask
(0.60mmol), TBHP (6mmol) and solvent ethyl acetate 5mL, then the system heats 16 hours under the conditions of 100 DEG C of tube sealing
Afterwards, with saturated sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous slufuric acid
Sodium dries organic layer, can obtain product 4a, yield 85% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.47
(d, J=8.3Hz, 2H), 5.81 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,8.7Hz, 1H), 2.26-2.14 (m,
1H),1.56(s,3H),1.49(s,3H),1.33(s,9H)；13C NMR(101MHz,CDCl3)δ171.92,165.04,
157.14,129.61,125.74,125.23,82.08,69.28,40.89,34.87,30.79,28.77,27.61；HRMS
(ESI-TOF):Anal.Calcd.For C17H22O4:219.1591,Found:219.1589(M+H+)。
Embodiment 10:
Reaction equation in the present embodiment are as follows:
Compound 1a (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI are sequentially loaded into reaction flask
(0.50mmol), TBHP (5mmol) and solvent ethyl acetate 5mL, then the system heats 12 hours under the conditions of 80 DEG C of tube sealing
Afterwards, with saturated sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous slufuric acid
Sodium dries organic layer, can obtain product 4a, yield 90% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.47
(d, J=8.3Hz, 2H), 5.81 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,8.7Hz, 1H), 2.26-2.14 (m,
1H),1.56(s,3H),1.49(s,3H),1.33(s,9H)；13C NMR(101MHz,CDCl3)δ171.92,165.04,
157.14,129.61,125.74,125.23,82.08,69.28,40.89,34.87,30.79,28.77,27.61；HRMS
(ESI-TOF):Anal.Calcd.For C17H22O4:219.1591,Found:219.1589(M+H+)。
Embodiment 11:
Reaction equation in the present embodiment are as follows:
It is sequentially loaded into reaction flask compound 1b (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), solvent ethyl acetate 5mL, then the system heats 12 hours under the conditions of 80 DEG C of tube sealing
Afterwards, with saturated sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous slufuric acid
Sodium dries organic layer, can obtain product 4b, yield 93% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.08 (d, J=7.7Hz, 2H), 7.60
(t, J=7.4Hz, 1H), 7.46 (t, J=7.6Hz, 2H), 5.81 (t, J=9.1Hz, 1H), 2.72 (dd, J=12.9,
8.8Hz, 1H), 2.21 (dd, J=12.7,9.8Hz, 1H), 1.57 (s, 3H), 1.51 (s, 3H)；13C NMR(101MHz,
CDCl3)δ172.03,165.31,133.64,129.89,128.60,128.42,82.31,69.57,41.13,28.97,
27.82；HRMS(ESI-TOF):Anal.Calcd.For C13H14O4:235.0965,Found:235.0964(M+H+)。
Embodiment 12:
It is sequentially loaded into reaction flask compound 1c (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), solvent ethyl acetate 5mL, then the system heats 12 hours under the conditions of 80 DEG C of tube sealing
Afterwards, with saturated sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous slufuric acid
Sodium dries organic layer, can obtain product 4c, yield 94% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 7.96 (d, J=7.8Hz, 2H), 7.96
(d, J=7.8Hz, 2H), 7.26 (t, J=8.0Hz, 2H), 7.25 (d, J=7.8Hz, 2H), 5.79 (t, J=9.1Hz, 1H),
5.79 (t, J=9.1Hz, 1H), 2.71 (dd, J=12.9,8.8Hz, 1H), 2.41 (s, 3H), 2.20 (dd, J=12.7,
9.7Hz,1H),1.57(s,3H),1.50(s,3H)；13C NMR(101MHz,CDCl3)δ172.13,165.32,144.45,
129.90,129.11,125.83,82.26,69.41,41.14,28.94,27.80,21.64；HRMS(ESI-TOF):
Anal.Calcd.For C14H16O4:249.1121,Found:249.1121(M+H+).
Embodiment 13:
It is sequentially loaded into reaction flask compound 1d (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), solvent ethyl acetate 5mL, then the system heats 12 hours under the conditions of 80 DEG C of tube sealing
Afterwards, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous sodium sulfate in saturated sodium sulfite quenching reaction
Dry organic layer can obtain product 4d, yield 91% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.03 (d, J=8.4Hz, 2H), 6.93
(d, J=8.4Hz, 2H), 5.78 (t, J=9.1Hz, 1H), 3.86 (s, 3H), 2.70 (dd, J=12.9,8.8Hz, 1H), 2.20
(dd, J=12.8,9.9Hz, 1H), 1.57 (s, 3H), 1.50 (s, 3H)；13C NMR(101MHz,CDCl3)δ172.23,
164.93,163.76,131.97,120.85,113.60,82.22,69.28,55.36,41.13,28.92,27.76；HRMS
(ESI-TOF):Anal.Calcd.For C14H16O5:265.1071,Found:265.1070(M+H+).
Embodiment 14:
It is sequentially loaded into reaction flask compound 1e (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), solvent ethyl acetate 5mL, then the system heats 12 hours under the conditions of 80 DEG C of tube sealing
Afterwards, with saturated sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous slufuric acid
Sodium dries organic layer, can obtain product 4e, yield 83% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=8.2Hz, 2H), 7.43
(d, J=8.2Hz, 2H), 5.80 (t, J=9.2Hz, 1H), 2.72 (dd, J=12.9,8.8Hz, 1H), 2.21 (dd, J=
12.8,9.8Hz,1H),1.57(s,3H),1.51(s,3H)；13C NMR(101MHz,CDCl3)δ171.78,164.39,
140.04,131.22,128.74,127.05,82.28,69.71,40.98,28.92,27.74；HRMS(ESI-TOF):
Anal.Calcd.For C13H13ClO4:269.0575,Found:269.0574(M+H+).
Embodiment 15:
It is sequentially loaded into reaction flask compound 1f (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, satisfy
With sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous sodium sulfate is dry
Organic layer can obtain product 4f, yield 85% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.10 (dd, J=7.4,5.7Hz, 2H),
7.14 (t, J=8.2Hz, 2H), 5.81 (t, J=9.2Hz, 1H), 2.73 (dd, J=12.8,8.8Hz, 1H), 2.22 (dd, J=
12.5,10.1Hz,1H),1.58(s,3H),1.51(s,3H)；13C NMR(101MHz,CDCl3)δ171.89,167.25,
164.72,164.26,132.55,132.45,124.87,124.84,115.72,115.50,82.28,69.63,41.00,
28.92,27.73；HRMS(ESI-TOF):Anal.Calcd.For C13H13FO4:253.0871,Found:253.0871(M+H
+).
Embodiment 16:
It is sequentially loaded into reaction flask compound 1g (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4g, yield 85% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 7.93 (d, J=8.0Hz, 2H), 7.60
(d, J=8.0Hz, 2H), 5.80 (t, J=9.2Hz, 1H), 2.72 (dd, J=12.9,8.8Hz, 1H), 2.20 (dd, J=
22.1,9.4Hz,1H),1.57(s,3H),1.51(s,3H)；13C NMR(101MHz,CDCl3)δ171.76,164.53,
131.73,131.32,128.80,127.48,82.28,69.71,40.95,28.92,27.74；HRMS(ESI-TOF):
Anal.Calcd.For C13H13BrO4:313.0070,Found:313.0070(M+H+)。
Embodiment 17:
It is sequentially loaded into reaction flask compound 1h (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4h, yield 89% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.13 (d, J=8.3Hz, 2H), 7.66
(d, J=8.3Hz, 2H), 7.61 (d, J=7.4Hz, 2H), 7.46 (t, J=7.4Hz, 2H), 7.39 (t, J=7.2Hz, 1H),
5.81 (t, J=9.1Hz, 1H), 2.71 (dd, J=13.0,8.7Hz, 1H), 2.21 (dd, J=12.9,9.5Hz, 1H), 1.57
(s,3H),1.50(s,3H)；13C NMR(101MHz,CDCl3)δ171.96,165.17,146.26,139.60,130.42,
128.86,128.23,127.37,127.17,127.03,82.23,69.62,41.19,28.97,27.82；HRMS(ESI-
TOF):Anal.Calcd.For C19H18O4:311.1278,Found:311.1277(M+H+).
Embodiment 18:
It is sequentially loaded into reaction flask compound 1i (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4i, yield 78% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.20 (d, J=8.1Hz, 2H), 7.73
(d, J=8.2Hz, 2H), 5.84 (t, J=9.2Hz, 1H), 2.74 (dd, J=13.0,8.8Hz, 1H), 2.24 (dd, J=
12.9,9.7Hz,1H),1.59(s,3H),1.52(s,3H)；13C NMR(101MHz,CDCl3)δ171.63,164.24,
135.56,135.23,134.90,134.58,132.06,130.41,125.57,125.54,125.50,124.85,122.14,
82.41,70.14,41.14,29.05,27.89；HRMS(ESI-TOF):Anal.Calcd.For C14H13F3O4:303.0839,
Found:303.0837(M+H+)。
Embodiment 19:
It is sequentially loaded into reaction flask compound 1j (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, satisfy
With sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous sodium sulfate is dry
Organic layer can obtain product 4j, yield 78% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 7.98 (d, J=7.6Hz, 1H), 7.43
(t, J=7.4Hz, 1H), 7.25 (t, J=7.1Hz, 2H), 5.80 (t, J=9.1Hz, 1H), 2.70 (dd, J=12.9,
8.7Hz, 1H), 2.61 (s, 3H), 2.19 (dd, J=12.9,9.6Hz, 1H), 1.56 (s, 3H), 1.49 (s, 3H)；13C NMR
(101MHz,CDCl3)δ172.04,165.92,140.78,132.63,131.69,130.88,127.85,125.72,82.16,
69.26,41.16,28.94,27.75,21.69；HRMS(ESI-TOF):Anal.Calcd.For C14H16O4:249.1121,
Found:249.1121(M+H+)。
Embodiment 20:
It is sequentially loaded into reaction flask compound 1k (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4k, yield 86% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 7.88 (d, J=7.8Hz, 1H), 7.50
(t, J=7.8Hz, 1H), 6.98 (t, J=7.3Hz, 2H), 5.76 (t, J=8.9Hz, 1H), 3.90 (s, 3H), 2.69 (dd, J
=13.0,8.7Hz, 1H), 2.19 (dd, J=12.9,9.2Hz, 1H), 1.55 (s, 3H), 1.49 (s, 3H)；13C NMR
(101MHz,CDCl3)δ172.06,164.34,159.58,134.32,131.97,119.99,118.05,111.95,82.25,
69.28,55.81,41.18,28.82,27.78；HRMS(ESI-TOF):Anal.Calcd.For C14H16O5:265.1071,
Found:265.1069(M+H+)。
Embodiment 21:
It is sequentially loaded into reaction flask compound 1l (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4l, yield 75% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 7.90 (dd, J=6.3,2.9Hz, 1H),
7.68 (d, J=8.6Hz, 1H), 7.38 (p, J=7.3Hz, 2H), 5.82 (t, J=9.1Hz, 1H), 2.74 (dd, J=13.0,
8.8Hz,1H),2.29–2.18(m,1H),1.57(s,3H),1.50(s,3H)；13C NMR(101MHz,CDCl3)δ171.56,
164.58,134.44,133.24,131.81,130.31,127.23,122.06,82.34,69.96,40.99,28.97,
27.80；HRMS(ESI-TOF):Anal.Calcd.For C13H13BrO4:313.0070,Found:313.0069(M+H+)。
Embodiment 22:
It is sequentially loaded into reaction flask compound 1m (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4m, yield 88% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=7.9Hz, 1H), 7.91
(d, J=7.8Hz, 1H), 7.42 (t, J=7.6Hz, 1H), 7.19 (dd, J=11.0,4.3Hz, 1H), 5.82 (t, J=
9.1Hz, 1H), 2.75 (dd, J=13.0,8.7Hz, 1H), 2.24 (dd, J=12.9,9.6Hz, 1H), 1.57 (s, 3H), 1.50
(s,3H)；13C NMR(101MHz,CDCl3)δ171.51,164.85,141.42,133.27,133.01,131.47,127.94,
94.40,82.28,69.98,40.93,28.95,27.73；HRMS(ESI-TOF):Anal.Calcd.For C13H13IO4:
360.9931,Found:360.9931(M+H+)。
Embodiment 23:
It is sequentially loaded into reaction flask compound 1n (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(50mol%), TBHP (5mmol), ethyl acetate 5mL, after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, with full
With sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous sodium sulfate is dry
Organic layer can obtain product 4n, yield 90% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 7.91 (d, J=7.7Hz, 1H), 7.54
(t, J=7.5Hz, 1H), 7.45-7.33 (m, 5H), 7.30 (d, J=6.7Hz, 2H), 5.63 (t, J=9.0Hz, 1H), 2.35
(dd, J=13.1,8.8Hz, 1H), 1.63 (dd, J=13.0,9.2Hz, 1H), 1.36 (s, 3H), 1.34 (s, 3H)；13C NMR
(101MHz,CDCl3)δ171.49,166.90,142.86,141.10,131.79,130.71,130.21,129.16,
128.43,127.93,127.17,82.00,69.12,40.23,28.72,27.67；HRMS(ESI-TOF):
Anal.Calcd.For C19H18O4:311.1278,Found:311.1278(M+H+)。
Embodiment 24:
It is sequentially loaded into reaction flask compound 1o (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(50mol%), TBHP (5mmol), ethyl acetate 5mL, after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, with full
With sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous sodium sulfate is dry
Organic layer can obtain product 4o, yield 87% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 7.87 (d, J=8.5Hz, 2H), 7.39
(d, J=7.5Hz, 1H), 7.33 (t, J=7.5Hz, 1H), 5.77 (t, J=9.0Hz, 1H), 2.70 (dd, J=13.0,
8.7Hz, 1H), 2.40 (s, 3H), 2.19 (dd, J=13.0,9.4Hz, 1H), 1.56 (s, 3H), 1.50 (s, 3H)；13C NMR
(101MHz,CDCl3)δ171.91,165.53,138.31,134.38,130.42,128.79,128.35,127.12,82.15,
69.63,41.37,29.05,27.92,21.14；HRMS(ESI-TOF):Anal.Calcd.For C14H16O4:249.1121,
Found:249.1121(M+H+)。
Embodiment 25:
It is sequentially loaded into reaction flask compound 1p (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(50mol%), TBHP (5mmol), ethyl acetate 5mL, after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, with full
With sodium sulfite quenching reaction, (20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times, anhydrous sodium sulfate is dry
Organic layer can obtain product 4p, yield 86% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 7.66 (d, J=7.7Hz, 1H), 7.57
(s, 1H), 7.35 (t, J=8.0Hz, 1H), 7.13 (dd, J=8.2,2.1Hz, 1H), 5.78 (t, J=9.0Hz, 1H), 3.85
(s, 3H), 2.69 (dd, J=13.0,8.7Hz, 1H), 2.20 (dd, J=13.0,9.3Hz, 1H), 1.57 (s, 3H), 1.50 (s,
3H)；13C NMR(101MHz,CDCl3)δ171.79,165.26,159.67,130.13,129.50,122.39,120.19,
114.43,82.17,77.32,77.00,76.68,69.77,55.46,41.31,29.04,27.94；HRMS(ESI-TOF):
Anal.Calcd.For C14H16O5:265.1071,Found:265.1071(M+H+)。
Embodiment 26:
It is sequentially loaded into reaction flask compound 1q (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4q, yield 80% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 7.87 (d, J=7.7Hz, 1H), 7.74
(d, J=9.1Hz, 1H), 7.44 (dd, J=13.5,8.0Hz, 1H), 7.33-7.25 (m, 1H), 5.79 (t, J=9.1Hz,
1H), 2.71 (dd, J=13.0,8.8Hz, 1H), 2.21 (dd, J=13.0,9.5Hz, 1H), 1.57 (s, 3H), 1.50 (s,
3H)；13C NMR(101MHz,CDCl3)δ171.54,164.26,164.23,163.74,161.28,131.02,130.94,
130.21,130.13,125.71,125.69,120.82,120.61,116.91,116.68,82.22,77.32,77.00,
76.68,69.97,41.20,29.03,27.88；HRMS(ESI-TOF):Anal.Calcd.For C13H13FO4:253.0871,
Found:253.0870(M+H+)。
Embodiment 27:
It is sequentially loaded into reaction flask compound 1r (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4r, yield 70% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.88 (s, 1H), 8.45 (d, J=
8.2Hz, 1H), 8.40 (d, J=7.8Hz, 1H), 7.68 (t, J=8.0Hz, 1H), 5.86 (t, J=9.2Hz, 1H), 2.73
(dd, J=13.0,8.8Hz, 1H), 2.27 (dd, J=12.9,9.8Hz, 1H), 1.60 (s, 3H), 1.52 (s, 3H)；13C NMR
(101MHz,CDCl3)δ171.23,163.40,148.42,135.54,130.68,129.83,128.04,124.92,82.29,
70.36,41.09,29.09,27.92；HRMS(ESI-TOF):Anal.Calcd.For C13H13NO6:280.0816,Found:
280.0815(M+H+)。
Embodiment 28:
It is sequentially loaded into reaction flask compound 1s (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(50mol%), TBHP (5mmol), ethyl acetate 5mL after then the system heats about 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4s, yield 84% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.93 (d, J=8.7Hz, 1H), 8.27
(d, J=7.3Hz, 1H), 8.03 (d, J=8.2Hz, 1H), 7.87 (d, J=8.2Hz, 1H), 7.62 (t, J=7.7Hz, 1H),
7.50 (dt, J=18.2,7.7Hz, 2H), 5.90 (t, J=9.1Hz, 1H), 2.73 (dd, J=13.0,8.8Hz, 1H), 2.23
(dd, J=13.0,9.5Hz, 1H), 1.55 (s, 3H), 1.50 (s, 3H)；13C NMR(101MHz,CDCl3)δ171.99,
165.98,134.15,133.78,131.38,130.95,128.57,128.05,126.31,125.55,125.41,124.38,
82.20,69.62,41.32,29.02,27.87；HRMS(ESI-TOF):Anal.Calcd.For C17H16O4:285.1121,
Found:285.1121(M+H+)。
Embodiment 29:
It is sequentially loaded into reaction flask compound 1t (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4t, yield 89% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.63 (s, 1H), 8.05 (dd, J=
8.6,1.3Hz, 1H), 7.92 (d, J=8.0Hz, 1H), 7.85 (dd, J=8.3,3.9Hz, 2H), 7.55 (ddd, J=21.4,
14.0,6.9Hz, 2H), 5.85 (t, J=9.1Hz, 1H), 2.72 (dd, J=13.0,8.8Hz, 1H), 2.24 (dd, J=13.0,
9.4Hz,1H),1.56(s,3H),1.49(s,3H)；13C NMR(101MHz,CDCl3)δ171.88,165.41,135.70,
132.29,131.62,129.30,128.51,128.21,127.67,126.71,125.97,125.06,82.15,69.76,
41.26,28.96,27.81；HRMS(ESI-TOF):Anal.Calcd.For C17H16O4:285.1121,Found:285.1121
(M+H+)。
Embodiment 30:
It is sequentially loaded into reaction flask compound 1u (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4u, yield 89% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.81 (d, J=5.5Hz, 2H), 7.87
(d, J=5.6Hz, 2H), 5.82 (t, J=9.1Hz, 1H), 2.72 (dd, J=13.0,8.8Hz, 1H), 2.23 (dd, J=
13.0,9.5Hz,1H),1.58(s,3H),1.51(s,3H)；13C NMR(101MHz,CDCl3)δ171.16,164.00,
150.68,136.03,122.90,82.28,70.28,41.03,29.00,27.84；HRMS(ESI-TOF):
Anal.Calcd.For C12H13NO4:236.0917,Found:236.0917(M+H+)。
Embodiment 31:
It is sequentially loaded into reaction flask compound 1v (1mmol), compound 2a (5mmol), 3a (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4v, yield 85% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 7.86 (d, J=3.7Hz, 1H), 7.62
(d, J=4.9Hz, 1H), 7.12 (t, J=4.3Hz, 1H), 5.75 (t, J=9.0Hz, 1H), 2.66 (dd, J=13.0,
8.7Hz, 1H), 2.21 (dd, J=13.0,9.3Hz, 1H), 1.56 (s, 3H), 1.48 (s, 3H)；13C NMR(101MHz,
CDCl3)δ171.51,160.73,134.46,133.47,131.98,127.84,82.16,69.67,41.04,28.89,
27.81；HRMS(ESI-TOF):Anal.Calcd.For C11H12O4S:241.0529,Found:241.0528(M+H+)。
Embodiment 32:
It is sequentially loaded into reaction flask compound 1a (1mmol), compound 2a (5mmol), 3b (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4w, yield 67% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.00 (d, J=7.4Hz, 2H), 7.47
(d, J=7.4Hz, 2H), 5.71 (t, J=9.1Hz, 1H), 2.67 (dd, J=12.5,10.2Hz, 1H), 2.11 (dd, J=
12.8,9.6Hz,1H),1.87–1.64(m,4H),1.34(s,10H),1.02–0.89(m,6H)；13C 13C NMR(101MHz,
CDCl3)δ172.39,165.48,157.47,129.88,126.01,125.46,87.54,69.30,37.12,35.14,
31.63,31.05,30.89,7.93,7.55；HRMS(ESI-TOF):Anal.Calcd.For C19H26O4:319.1904,
Found:319.1904(M+H+)。
Embodiment 33:
It is sequentially loaded into reaction flask compound 1a (1mmol), compound 2a (5mmol), 3c (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4x, yield 65% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.01 (d, J=7.5Hz, 2H), 7.47
(d, J=7.6Hz, 2H), 5.76 (t, J=9.0Hz, 1H), 2.74 (dd, J=12.7,8.4Hz, 1H), 2.46-2.35 (m,
1H), 2.17 (d, J=13.9Hz, 1H), 2.02 (d, J=8.7Hz, 1H), 1.89 (d, J=11.8Hz, 2H), 1.78 (d, J=
5.5Hz, 3H), 1.34 (s, 9H), 1.27 (d, J=11.4Hz, 3H)；13C NMR(101MHz,CDCl3)δ172.12,165.50,
157.52,129.92,126.04,125.50,92.10,69.50,39.22,39.15,38.84,35.19,31.09,24.16,
23.32；HRMS(ESI-TOF):Anal.Calcd.For C19H24O4:317.1747,Found:317.1748(M+H+)。
Embodiment 34:
It is sequentially loaded into reaction flask compound 1a (1mmol), compound 2a (5mmol), 3d (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4y, yield 74% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.00 (d, J=7.7Hz, 2H), 7.47
(d, J=7.7Hz, 2H), 5.73 (t, J=9.0Hz, 1H), 2.72 (dd, J=12.9,9.2Hz, 1H), 2.06 (dd, J=
12.7,9.5Hz, 1H), 1.89 (dd, J=24.0,14.2Hz, 2H), 1.79-1.63 (m, 4H), 1.54 (s, 2H), 1.34 (s,
9H), 1.27 (d, J=11.4Hz, 2H)；13C NMR(101MHz,CDCl3)δ172.21,165.50,157.51,129.92,
126.06,125.50,84.25,69.08,39.98,38.25,37.03,35.18,31.09,24.78,22.55,22.41；
HRMS(ESI-TOF):Anal.Calcd.For C20H26O4:331.1904,Found:331.1902(M+H+)。
Embodiment 35:
It is sequentially loaded into reaction flask compound 1a (1mmol), compound 2a (5mmol), 3e (50mmol), TBAI
(0.50mmol), TBHP (5mmol), ethyl acetate 5mL after then the system heats 12 hours under the conditions of 80 DEG C of tube sealing, are used
(20mL × 3), saturated common salt water washing is extracted with ethyl acetate three times in saturated sodium sulfite quenching reaction, and anhydrous sodium sulfate is dry
Dry organic layer can obtain product 4z, yield 85% by simple column chromatography.
Product is analyzed, as a result as follows:1H NMR(400MHz,CDCl3) δ 8.00 (d, J=8.3Hz, 2H), 7.47
(d, J=7.7Hz, 2H), 5.76 (dt, J=17.6,9.1Hz, 1H), 2.68 (ddd, J=46.4,12.5,9.3Hz, 1H),
2.23-2.07 (m, 1H), 1.88-1.67 (m, 2H), 1.46 (s, 3H), 1.34 (s, 9H), 1.01 (t, J=7.4Hz, 3H)；13C
NMR(101MHz,CDCl3)δ172.20,172.08,165.31,157.39,129.80,125.95,125.39,85.18,
84.55,69.48,69.17,39.38,39.11,35.07,34.40,33.62,30.98,26.46,25.24,8.25,7.79；
HRMS(ESI-TOF):Anal.Calcd.For C18H24O4:305.1747,Found:305.1746(M+H+)。
It should be noted that being used to help understand the present invention above for the explanation of these embodiments, but not
Constitute limitation of the invention.As long as in addition, technical characteristic involved in each embodiment of the present invention described above
Not constituting a conflict with each other can be combined with each other.In addition the above is only section Examples of the invention, rather than all real
Example is applied, based on the embodiments of the present invention, those of ordinary skill in the art are obtained without making creative work
The every other embodiment obtained, shall fall within the protection scope of the present invention.
Claims (7)
1. a kind of preparation method of gamma lactone derivative, which comprises the following steps: with aromatic derivant carboxylate,
Alkene derivatives and alcohol are reaction substrate, using halide as catalyst, in the presence of oxidant, and 60-100 DEG C of reaction temperature,
Gamma lactone derivative is prepared within 8-16 hours between seasonable；
Wherein:
The chemical structural formula of the aromatic derivant carboxylate isR in formula1It is selected from: naphthalene, heterocycle or monosubstituted virtue
BaseR2It is selected from: hydrogen, methyl, normal-butyl, methoxyl group, fluorine, chlorine, bromine, iodine, phenyl, trifluoromethyl or nitro；It is described miscellaneous
Ring is selected from thienyl or pyridyl group；
The chemical structural formula of the alkene derivatives is
The chemical structural formula of the 01 derivatives is
The halide is selected from: one of sodium iodide, potassium iodide, tetrabutylammonium iodide or tetrabutylammonium chloride；
The oxidant is selected from: one in tert-butyl hydroperoxide, di-t-butyl peroxide, hydrogen peroxide or potassium peroxydisulfate complex salt
Kind；
The dosage of the alkene is 4~6 times of the amount of the substance of the aromatic derivant carboxylate；
The dosage of the alcohol is 40~60 times of the amount of the substance of the aromatic derivant carboxylate；
The dosage of the catalyst is the 40%~60% of the amount of the substance of the aromatic derivant carboxylate；
The dosage of the oxidant is 4~6 times of the amount of the substance of the aromatic derivant carboxylate.
2. the preparation method of gamma lactone derivative as described in claim 1, which is characterized in that the dosage of the alkene is institute
5 times for stating the amount of the substance of aromatic derivant carboxylate.
3. the preparation method of gamma lactone derivative as described in claim 1, which is characterized in that the dosage of the alcohol is described
50 times of the amount of the substance of aromatic derivant carboxylate.
4. the preparation method of gamma lactone derivative as described in claim 1, which is characterized in that the dosage of the catalyst is
The 50% of the amount of the substance of the aromatic derivant carboxylate.
5. the preparation method of gamma lactone derivative as described in claim 1, which is characterized in that the dosage of the oxidant is
5 times of the amount of the substance of the aromatic derivant carboxylate.
6. the preparation method of gamma lactone derivative as described in claim 1, which is characterized in that the reaction temperature is 80 DEG C；
Reaction time 12 hours.
7. the preparation method of gamma lactone derivative as described in claim 1, which is characterized in that it is described reaction in a solvent into
Row, the solvent are acetonitrile, tetrahydrofuran, ethyl acetate, dioxane or n,N-Dimethylformamide.
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| CN113105416A (en) * | 2021-04-09 | 2021-07-13 | 万华化学集团股份有限公司 | Method for preparing gamma-lactone compounds |
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