CN112961115A - Method and compound for preparing (E) -alpha-aryl-alpha, beta-unsaturated oxazoline or carboxylic acid - Google Patents
Method and compound for preparing (E) -alpha-aryl-alpha, beta-unsaturated oxazoline or carboxylic acid Download PDFInfo
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Abstract
The invention discloses a method for preparing (E) -alpha-aryl-alpha, beta-unsaturated oxazoline or carboxylic acid, which comprises the following steps: in the presence of TMSOTf and alkali, aryl high-valence iodine shown in a structural formula (I) and alpha, beta-unsaturated oxazoline shown in a structural formula (II) react in a solvent to synthesize (E) -alpha-aryl-alpha, beta-unsaturated oxazoline shown in a structural formula (III), and finally, the (E) -alpha, beta-unsaturated carboxylic acid shown in a structural formula (II) is obtained by hydrolysis under an acidic condition. The method synthesizes (E) -alpha-aryl-alpha, beta-unsaturated oxazoline under mild conditions by aryl high-valence iodine and alpha, beta-unsaturated oxazoline, and finally obtains (E) -alpha-aryl-alpha, beta-unsaturated carboxylic acid by hydrolysis under acidic conditions. The method has the advantages of mild reaction conditions, wide substrate application range, good selectivity, high yield, easy product separation and simple operation.
Description
Technical Field
The invention belongs to the field of organic chemical synthesis, and particularly relates to a method and a compound for preparing (E) -alpha-aryl-alpha, beta-unsaturated oxazoline or carboxylic acid.
Background
Alpha-aryl-alpha, beta-unsaturated carbonyl building blocks are an important class of organic functional groups. The fragment is widely present in drugs and natural products. For example, cocaldehyde in perfume cosmetics, glycitein, perampanel, isoflavone, and luteolin, a natural product of anti-inflammatory and antiviral drugs, all contain α -aryl- α, β -unsaturated carbonyl fragments. Therefore, the synthesis of α -aryl- α, β -unsaturated carbonyl groups is one of the important research targets of synthetic chemistry.
Conventional α -aryl- α, β -unsaturated carbonyl compounds require synthesis through multiple reactions. For example, alpha-halogen (or metal) -alpha, beta-unsaturated carbonyl compounds are synthesized by nucleophilic substitution reaction, and then coupled with aromatic hydrocarbon metal reagent or halogenated aromatic hydrocarbon to obtain alpha-aryl-alpha, beta-unsaturated carbonyl compounds (J.Org.chem.2006,71, 5743-5747; tetrahedron.1997,53, 16711-16720). In addition, in 2009, chengweiwu project group reported that the synthesis of α -aryl- α, β -unsaturated carbonyl compounds was achieved using benzyl bromide and α -aryldiazoacetic acid methyl ester under palladium catalysis (org. lett.2009,11, 469-. This reaction also has the problem that the diazo starting material is not readily available.
In 2004, the Krische group discovered that arylation of α -C-H bond of 2-cyclohexen-1-one (or 2-cyclopenten-1-one) could be achieved using tributylphosphine as a catalyst and aryl bismuth as an arylating agent (j.am. chem. soc.2004,126, 5350-5351.). Although the reaction conditions are mild and the selectivity is excellent, the reaction needs an organic bismuth reagent which is not easy to obtain, and the application range of the substrate is narrow.
Wangwen adopts a strategy of organic small molecule catalysis in 2011 to realize the alpha-C-H bond arylation reaction of alpha, beta-unsaturated aldehyde (nat. Commun.2011,2, 524-534.). The reaction does not need metal participation, is environment-friendly and has high selectivity, but the reaction is only suitable for aromatic hydrocarbon substrates with electron-withdrawing functional groups.
In summary, the α -C-H bond arylation of α, β -unsaturated carbonyl compounds is still a problem to be solved in synthetic chemistry.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a novel method for preparing (E) -alpha-aryl-alpha, beta-unsaturated oxazoline or (E) -alpha-aryl-alpha, beta-unsaturated carboxylic acid, and the method has the advantages of mild reaction conditions, wide substrate application range, good selectivity, higher yield, easy product separation, simple operation and the like.
The invention also provides a (E) -alpha-aryl-alpha, beta-unsaturated oxazoline or (E) -alpha-aryl-alpha, beta-unsaturated carboxylic acid compound, and various important derivative compounds can be obtained by utilizing the compounds; and the above (E) -alpha-aryl-alpha, beta-unsaturated oxazoline or (E) -alpha-aryl-alpha, beta-unsaturated carboxylic acid itself can be sold as an important organic intermediate.
The technical scheme adopted by the invention is as follows:
a method for preparing (E) -alpha-aryl-alpha, beta-unsaturated carboxylic acid comprises the steps of reacting aryl high-valence iodine shown in a structural formula (I) with alpha, beta-unsaturated oxazoline shown in a structural formula (II) in a solvent in the presence of an activating agent (preferably TMSOTf, namely trimethylsilyl trifluoromethanesulfonate) and alkali to synthesize (E) -alpha-aryl-alpha, beta-unsaturated oxazoline shown in a structural formula (III), and finally hydrolyzing under an acidic condition to obtain the (E) -alpha, beta-unsaturated carboxylic acid shown in the structural formula (II). The general formula of the reaction is as follows:
wherein R is1Selected from hydrogen, halogen, alkyl, alkoxy, substituted alkoxy, amido or aryl, heteroaryl; r1Represents one or more substituents substituted on the aromatic ring in the above formula, and the substituents are independent of each other, and may be the same or different; r2Selected from hydrogen, alkyl, cycloalkyl and aryl.
The mechanism of the reaction is shown below:
we have constructed, by means of the MBH reaction, a rearrangement precursor IM of our [3,3] -sigma rearrangement reaction, thus developing an "assembly/addition" type of [3,3] -sigma rearrangement reaction. Specifically, the rearrangement reaction is carried out in four stages, including: (1) electrophilic 'assembly' of activated aryl hypervalent iodine with alpha, beta unsaturated oxazoline; (2) introducing Lewis base to carry out 1, 4-addition to construct an enol salt type intermediate IM; (3) carrying out [3,3] -rearrangement and aromatization on the intermediate IM; (4) elimination by β -H gives a product, thereby effecting MBH type [3,3] - σ rearrangement reactions. Finally hydrolyzing the rearrangement product under acidic condition to obtain (E) -alpha, beta-unsaturated carboxylic acid
Preferably, in the structural formulae (I) to (IV), R1Selected from hydrogen, halogen, C1～C4Alkyl radical, C1～C3Alkoxy, substituted C1～C3Alkoxy, amido or heteroaryl; r2Selected from hydrogen, C1～C4Alkyl radical, C3～C6Cycloalkyl and aryl. As a particularly preferred embodiment, said R1Selected from hydrogen, cyanomethoxy, methyl; r1Selected from hydrogen, methyl, ethyl, propyl, and the like.
Preferably, the feeding molar ratio of the aryl high-valence iodine to an activating agent (preferably TMSOTf) is 1: 1-2; as a further preference, the aryl hypervalent iodine to activator (preferably TMSOTf) feed molar ratio is 1: 2.
Preferably, the feeding molar ratio of the aryl high-valence iodine to the alpha, beta-unsaturated oxazoline is 1: 1-2; more preferably, the molar ratio of the aryl higher iodine to the alpha, beta-unsaturated oxazoline is 1: 2.
Preferably, the feeding molar ratio of the activating agent (preferably TMSOTf) to the Lewis base is 1: 1.1-2; as a further preference, the activator (preferably TMSOTf) is dosed in a molar ratio to lewis base of 1: 2.
The solvent used in the present invention is dichloromethane.
The Lewis base used in the present invention is a tertiary amine or a pyridine base, preferably 4-methylpyridine.
The reaction temperature is-80-0 ℃, and the reaction time is 12-36 h; the reaction temperature is preferably-80 to-10 ℃ and the reaction time is 24 hours.
Preferably, the acid used for hydrolysis is hydrochloric acid or sulfuric acid or an aqueous solution of the above acid, and more preferably, the acid used for hydrolysis is HCl (3.5M) or H2SO4(4M)/dioxane(1/1)。
In the present invention, the configuration of the product is E formula.
Compared with the prior art, the method synthesizes (E) -alpha-aryl-alpha, beta-unsaturated oxazoline under mild conditions by aryl high-valence iodine and an alpha, beta-unsaturated oxazoline compound, and then synthesizes (E) -alpha-aryl-alpha, beta-unsaturated carboxylic acid by hydrolysis, and has the advantages that: the advantages are that:
(1) the method has the advantages of mild reaction conditions, wide substrate application range, good selectivity, high yield, easy product separation and simple operation;
(2) the raw materials used in the method are cheap and easy to obtain, and the defects that the traditional method uses an organic metal reagent, the reaction condition requirements are strict, and the reaction substrate is limited are avoided;
(3) no matter the configuration of the raw material alpha, beta-unsaturated oxazoline is Z formula or E formula, the product is a single E formula, and a new reaction strategy is provided for the synthesis of (E) -alpha-aryl-alpha, beta-unsaturated carboxylic acid.
Drawings
FIG. 1 is a NOE spectrum of the product obtained in example 2.
FIG. 2 is a NOE spectrum of the product obtained in example 3.
FIG. 3 is a NOE spectrum of the product obtained in example 5.
FIG. 4 is a single crystal diagram of the product obtained in example 6, which was subjected to X-ray test.
Detailed Description
Example 1
TMSOTf (181. mu.L, 1.0mmol) was added to a solution of iodobenzene diacetate (161mg,0.5mmol) in DCM (5mL) at-78 deg.C, and after stirring for 15min, the mixture was added to an α, β -unsaturated oxazoline compound represented by the above formulaSubstance (97.1mg,1.0 mmol). After stirring for 15min, 4-methylpyridine (93mg, 1.0mmol) was added. Then gradually heating to-10 ℃, continuing to react for 24h, and then adding saturated NaHCO3The reaction was quenched with aqueous solution (5mL) and extracted with DCM (10 mL. times.3). The organic phase is passed through anhydrous Na2SO4After drying, concentration and purification by column chromatography (Rf 0.32, developing solvent: petroleum ether/ethyl acetate 2/1, v/v) gave the product 2- (1- (2-iodophenyl) vinyl) -oxazoline as a colorless oily liquid, 106.2mg, 71% yield.
1H NMR(600MHz,CDCl3):δ7.86(dd,J＝7.9,0.9Hz,1H),7.37–7.34(m,1H),7.31–7.26(m,1H),7.03–7.00(m,1H),6.27(s,1H),5.61(s,1H),4.38(t,J＝9.5Hz,2H),3.97(t,J＝9.5Hz,2H).
13C NMR(151MHz,CDCl3):δ163.7,143.3,140.8,139.2,130.1,129.5,128.2,125.5,98.9,67.8,55.6.
IR(neat):3048,2927,2873,2170,1646,1601,1178,725.
HRMS(ESI-TOF):calculated for[C11H11INO(M+H+)]:299.9880,found:299.9882.
Example 2
TMSOTf (181. mu.L, 1.0mmol) was added to a solution of iodobenzene diacetate (161mg,0.5mmol) in DCM (5mL) at-78 deg.C, and after stirring for 15min, the α, β -unsaturated oxazoline compound (111.1mg,1.0mmol) represented by the above formula was added to the mixture. After stirring for 15min, 4-methylpyridine (93mg, 1.0mmol) was added. Then gradually heating to-10 ℃, continuing to react for 24h, and then adding saturated NaHCO3The reaction was quenched with aqueous solution (5mL) and extracted with DCM (10 mL. times.3). The organic phase is passed through anhydrous Na2SO4After drying, concentration and purification by column chromatography (Rf 0.37, developing solvent: petroleum ether/ethyl acetate 2/1, v/v) gave the product (E) -2- (1- (2-iodophenyl) prop-1-en-1-yl) -oxazoline as a colorless oily liquid, 112.7mg, 72% yield.
1H NMR(600MHz,CDCl3):δ7.88(d,J＝7.9Hz,1H),7.38–4.35(m,1H),7.17(dd,J＝7.6,1.5Hz,1H),7.03–6.98(m,1H),6.84(q,J＝7.0Hz,1H),4.38–4.26(m,2H),3.94–3.89(m,2H),1.60(d,J＝7.1Hz,3H).
13C NMR(151MHz,CDCl3):δ164.2,141.3,139.2,136.3,134.2,130.4,129.2,128.3,100.0,67.5,55.3,15.3.
IR(neat):3053,2940,2888,2872,2283,1916,1618,753.
HRMS(ESI-TOF):calculated for[C12H13INO(M+H+)]:314.0036,found:314.0036.
FIG. 1 is the NOE spectrum of the product, confirming the product configuration as E configuration.
Example 3
TMSOTf (181. mu.L, 1.0mmol) was added to a solution of iodobenzene diacetate (161mg,0.5mmol) in DCM (5mL) at-78 deg.C, and after stirring for 15min, the α, β -unsaturated oxazoline compound (139.2mg,1.0mmol) represented by the above formula was added to the mixture. After stirring for 15min, 4-methylpyridine (93mg, 1.0mmol) was added. Then gradually heating to-10 ℃, continuing to react for 24h, and then adding saturated NaHCO3The reaction was quenched with aqueous solution (5mL) and extracted with DCM (10 mL. times.3). The organic phase is passed through anhydrous Na2SO4After drying, concentration and purification by column chromatography (Rf 0.27, developing solvent: petroleum ether/ethyl acetate 2/1, v/v) gave the product (E) -2- (1- (2-iodophenyl) pent-1-en-1-yl) -oxazoline as a colorless oily liquid 117.7mg, 69% yield.
1H NMR(600MHz,CDCl3):δ7.87(dd,J＝8.0,1.1Hz,1H),7.37–7.34(m,1H),7.16(dd,J＝7.6,1.7Hz,1H),7.01–6.99(m,1H),6.76(t,J＝7.6Hz,1H),4.37–4.25(m,2H),3.93–3.89(m,2H),1.97–1.83(m,2H),1.50–1.39(m,2H),0.87(t,J＝7.4Hz,3H).
13C NMR(151MHz,CDCl3):δ164.0,141.5,141.2,139.0,133.1,130.2,129.1,128.0,100.1,67.3,55.2,31.4,21.7,14.0.
IR(neat):3053,2954,2888,2870,1916,1618,988,753.
HRMS(ESI-TOF):calculated for[C14H17INO(M+H+)]:342.0349,found:342.0347.
FIG. 2 is the NOE spectrum of the product, the product configuration being identified as the E configuration.
Example 4
TMSOTf (181. mu.L, 1.0mmol) was added to a solution of iodobenzene diacetate (161mg,0.5mmol) in DCM (5mL) at-78 deg.C, and after stirring for 15min, the α, β -unsaturated oxazoline compound (139.2mg,1.0mmol) represented by the above formula was added to the mixture. After stirring for 15min, 4-methylpyridine (93mg, 1.0mmol) was added. Then gradually heating to-10 ℃, continuing to react for 24h, and then adding saturated NaHCO3The reaction was quenched with aqueous solution (5mL) and extracted with DCM (10 mL. times.3). The organic phase is passed through anhydrous Na2SO4After drying, concentration and purification by column chromatography (Rf 0.27, developing solvent: petroleum ether/ethyl acetate 2/1, v/v) gave the product (E) -2- (1- (2-iodophenyl) pent-1-en-1-yl) -oxazoline as a colorless oily liquid, 116.0mg, in 68% yield.
1H NMR(600MHz,CDCl3):δ7.87(dd,J＝8.0,1.1Hz,1H),7.37–7.34(m,1H),7.16(dd,J＝7.6,1.7Hz,1H),7.01–6.99(m,1H),6.76(t,J＝7.6Hz,1H),4.37–4.25(m,2H),3.93–3.89(m,2H),1.97–1.83(m,2H),1.50–1.39(m,2H),0.87(t,J＝7.4Hz,3H).
13C NMR(151MHz,CDCl3):δ164.0,141.5,141.2,139.0,133.1,130.2,129.1,128.0,100.1,67.3,55.2,31.4,21.7,14.0.
IR(neat):3053,2954,2888,2870,1916,1618,988,753.
HRMS(ESI-TOF):calculated for[C14H17INO(M+H+)]:342.0349,found:342.0347.
Example 5
TMSOTf (181. mu.L, 1.0mmol) was added to a solution of iodobenzene diacetate (161mg,0.5mmol) in DCM (5mL) at-78 deg.C, and after stirring for 15min, the α, β -unsaturated oxazoline compound (179.3mg,1.0mmol) represented by the above formula was added to the mixture. After stirring for 15min, 4-methylpyridine (93mg, 1.0mmol) was added. Then gradually heating to-10 ℃, continuing to react for 24h, and then adding saturated NaHCO3The reaction was quenched with aqueous solution (5mL) and extracted with DCM (10 mL. times.3). The organic phase is passed through anhydrous Na2SO4After drying, concentration and purification by column chromatography (Rf 0.53, developing solvent: petroleum ether/ethyl acetate 2/1, v/v) gave the product (E) -2- (2-cyclohexyl-1- (2-iodophenyl) vinyl) -oxazoline as a colorless oily liquid, 106.6mg, 56% yield.
FIG. 3 is the NOE spectrum of the product, with the product configuration identified as the E configuration.
Example 6
TMSOTf (181. mu.L, 1.0mmol) was added to a solution of aryl hypervalent iodine (188.5mg,0.5mmol) represented by the above formula in DCM (5mL) at-78 deg.C, and after stirring for 15min, the α, β -unsaturated oxazoline compound (111.1mg,1.0mmol) represented by the above formula was added to the mixture. After stirring for 15min, 4-methylpyridine (93mg, 1.0mmol) was added. Then gradually heating to-10 ℃, continuing to react for 24h, and then adding saturated NaHCO3The reaction was quenched with aqueous solution (5mL) and extracted with DCM (10 mL. times.3). The organic phase is passed through anhydrous Na2SO4After drying, concentration and purification by column chromatography (Rf 0.16, developing solvent: petroleum ether/ethyl acetate 2/1, v/v) gave the product (E) -2- (4- (1- (azolin-2-yl) prop-1-en-1-yl) -3-iodophenoxy) acetonitrile as a white solid in 149.1mg, 81% yield. (and further define its structure by X-ray)
1H NMR(600MHz,CDCl3):δ7.48(d,J＝2.6Hz,1H),7.12(d,J＝8.4Hz,1H),7.01–6.99(m,1H),6.84(q,J＝7.1Hz,1H),4.72(s,2H),4.37–4.27(m,2H),3.92–3.88(m,2H),1.61(d,J＝7.1Hz,3H).
13C NMR(151MHz,CDCl3):δ164.2,155.9,136.9,136.2,133.2,131.0,125.5,114.9,100.2,67.5,55.2,53.7,15.3.
IR(neat):3312,2921,2159,2011,1715,1610,1510,990,749.
HRMS(ESI-TOF):calculated for[C14H13IN2O2Na(M+Na+)]:390.9914,found:390.9931.
We performed X-ray tests on the product obtained in this example, as shown in FIG. 4, further verifying the structure of formula E.
Example 7
TMSOTf (181. mu.L, 1.0mmol) was added to a solution of aryl hypervalent iodine (175mg,0.5mmol) represented by the above formula in DCM (5mL) at-78 deg.C, and after stirring for 15min, the α, β -unsaturated oxazoline compound (111.1mg,1.0mmol) represented by the above formula was added to the mixture. After stirring for 15min, 4-methylpyridine (93mg, 1.0mmol) was added. Then gradually heating to-10 ℃, continuing to react for 24h, and then adding saturated NaHCO3The reaction was quenched with aqueous solution (5mL) and extracted with DCM (10 mL. times.3). The organic phase is passed through anhydrous Na2SO4After drying, concentration and purification by column chromatography (Rf 0.38, developing solvent: petroleum ether/ethyl acetate 2/1, v/v) gave the product (E) -2- (1- (2-iodo-3, 4-dimethylphenyl) prop-1-en-1-yl) -oxazoline as a white solid in 141.6mg, 83% yield.
1H NMR(600MHz,CDCl3):δ7.12(d,J＝7.6Hz,1H),6.88(d,J＝7.6Hz,1H),6.81(q,J＝7.1Hz,1H),4.38–4.26(m,2H),3.92–3.89(m,2H),2.48(s,3H),2.35(s,3H),1.59(d,J＝7.1Hz,3H).
13C NMR(151MHz,CDCl3):δ164.4,140.3,139.9,136.3,135.7,135.5,129.8,127.3,108.3,67.4,55.3,26.3,22.0,15.2.
IR(neat):3288,2933,2857,2111,1670,1611,1094,989
HRMS(ESI-TOF):calculated for[C14H16INONa(M+Na+)]:364.0169,found:364.0182.
Example 8
2- (1- (2-iodophenyl) vinyl) -4, 5-dihydrooxazoline (1.88g, 6.3mmol) was dissolved in 3.5M HCl (100mL), stirred at 80 ℃ for 15h, cooled to room temperature, and concentrated. Extracting with DCM, and extracting the organic phase with anhydrous Na2SO4After drying, concentration was carried out to give 2- (2-iodophenyl) acrylic acid (CAS: 2353621-35-7) as a white solid, 1.69g, yield 98%. (Rf 0.28, developing solvent: dichloromethane/methanol 15/1).
1H NMR(600MHz,CDCl3):δ7.86(d,J＝7.9Hz,1H),7.37(dd,J＝10.8,4.1Hz,1H),7.26–7.23(m,1H),7.06–7.03(m,1H),6.67(s,1H),5.87(s,1H).
13C NMR(151MHz,CDCl3):δ170.2,144.1,142.0,139.1,131.5,130.3,129.8,128.3,98.9.
IR(neat):2923,1931,1685,1611,1418,1256,1219,1012,728.
HRMS(ESI-TOF):calculated for[C9H6IO2(M–H+)]:272.9418,found:272.9428.
Example 9
(E) -2- (1- (2-iodophenyl) propenyl) -4, 5-dihydrooxazoline (2.07g, 6.6mmol) was dissolved in H2SO4(4M)/dioxane (1/1,28mL), stirred at 90 ℃ for 18h, cooled to room temperature, neutralized with sodium hydroxide solution (2M), and concentrated. After dissolution in DCM, pH 1 was adjusted with hydrochloric acid (1M), then extracted with DCM and the organic phase with anhydrous Na2SO4After drying, concentration gave (E) -2- (2-iodophenyl) but-2-enoic acid as a white solid, 1.86g, 98% yield. (Rf 0.28, developing solvent: dichloromethane/methanol 15/1).
Claims (10)
1. A preparation method of (E) -alpha-aryl-alpha, beta-unsaturated oxazoline or carboxylic acid is characterized in that aryl hypervalent iodine shown in a structural formula (I) and alpha, beta-unsaturated oxazoline shown in a structural formula (II) react in a solvent in the presence of an activating agent and alkali to obtain (E) -alpha-aryl-alpha, beta-unsaturated oxazoline shown in a structural formula (III); optionally further hydrolyzing the (E) -alpha-aryl-alpha, beta-unsaturated oxazoline represented by the structural formula (III) to obtain the (E) -alpha-aryl-alpha, beta-unsaturated carboxylic acid.
Wherein R is1Selected from hydrogen, halogen, alkyl, alkoxy, substituted alkoxy, amino, amido or aryl, heteroaryl, R1Is one or more; r2Selected from hydrogen, alkyl, cycloalkyl and aryl.
2. The method for producing (E) - α -aryl- α, β -unsaturated oxazoline or carboxylic acid according to claim 1, wherein R is R1Selected from hydrogen, halogen, C1～C4Alkyl radical, C1～C3Alkoxy, substituted C1～C3Alkoxy, amido or heteroaryl; r2Selected from hydrogen, C1～C4Alkyl radical, C3～C6Cycloalkyl and aryl.
3. The method for producing an (E) - α -aryl- α, β -unsaturated oxazoline or carboxylic acid according to claim 1, wherein the molar ratio of the aryl hypervalent iodine to the activator is 1:1 to 2.
4. The method for producing an (E) - α -aryl- α, β -unsaturated oxazoline or carboxylic acid according to claim 1, wherein the molar ratio of the aryl higher iodine to the α, β -unsaturated oxazoline is 1:1 to 2.
5. The process for producing (E) - α -aryl- α, β -unsaturated oxazoline or carboxylic acid according to claim 1, wherein the base is a tertiary amine; the feeding molar ratio of the activating agent to the alkali is 1: 1.1-2.
6. The process for producing (E) - α -aryl- α, β -unsaturated oxazoline or carboxylic acid according to claim 1, wherein the solvent is methylene chloride; the activating agent is trimethylsilyl trifluoromethanesulfonate; the alkali is tertiary amine or pyridine alkali.
7. The method for producing (E) - α -aryl- α, β -unsaturated oxazoline or carboxylic acid according to claim 1, wherein the reaction temperature of the aryl hypervalent iodine with the α, β -unsaturated oxazoline is from-80 to 0 ℃ and the reaction time is from 12 to 36 hours.
8. The process for producing (E) - α -aryl- α, β -unsaturated oxazoline or carboxylic acid as claimed in claim 1, wherein the acid used for the hydrolysis is hydrochloric acid or sulfuric acid.
9. An (E) - α -aryl- α, β -unsaturated oxazoline having a structure represented by the structural formula (III):
wherein R is1Selected from hydrogen, halogen, alkyl, alkoxy, substituted alkoxy, amino, amido or aryl, heteroaryl, R1Is one or more; r2Selected from hydrogen, alkyl, cycloalkyl and aryl.
10. An (E) - α -aryl- α, β -unsaturated carboxylic acid having the structure of formula (IV):
wherein R is1Selected from hydrogen, halogen, alkyl, alkoxy, substituted alkoxy, amino, amido or aryl, heteroaryl, R1Is one or more; r2Selected from hydrogen, alkyl, cycloalkyl and aryl.
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|---|---|---|---|---|
| CN114773285A (en) * | 2022-03-25 | 2022-07-22 | 大连理工大学 | Efficient preparation method of alpha-amino oxazoline compound |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105566021A (en) * | 2015-12-30 | 2016-05-11 | 中国科学技术大学 | Preparation method of alpha, beta-unsaturated carboxylic acid compounds |
| CN109776295A (en) * | 2019-02-18 | 2019-05-21 | 浙江师范大学 | A kind of aryl iodine compound and preparation method of the ortho position containing difluoro methylene |
| CN109824501A (en) * | 2019-02-18 | 2019-05-31 | 浙江师范大学 | A kind of the aryl iodine compound and preparation method of ortho position difluoro methylene containing carboxylic |
-
2021
- 2021-02-27 CN CN202110221396.2A patent/CN112961115A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105566021A (en) * | 2015-12-30 | 2016-05-11 | 中国科学技术大学 | Preparation method of alpha, beta-unsaturated carboxylic acid compounds |
| CN109776295A (en) * | 2019-02-18 | 2019-05-21 | 浙江师范大学 | A kind of aryl iodine compound and preparation method of the ortho position containing difluoro methylene |
| CN109824501A (en) * | 2019-02-18 | 2019-05-31 | 浙江师范大学 | A kind of the aryl iodine compound and preparation method of ortho position difluoro methylene containing carboxylic |
Non-Patent Citations (4)
| Title |
|---|
| JUNSONG TIAN ET AL.: "Selective ortho C-H Cyanoalkylation of (Diacetoxyiodo)arenes through [3,3]-Sigmatropic Rearrangement", 《ANGEW.CHEM.INT.ED.》 * |
| 包王镇: "芳基高价碘参与的Morita-Baylis-Hillman型[3,3]-σ重排反应", 《中国优秀博硕士学位论文全文数据库(硕士)工程科技Ⅰ辑》 * |
| 彭勃 等: "芳基高价碘与烯丙基硅烷的[3,3]-重排反应研究进展", 《浙江师范大学学报(自然科学版)》 * |
| 彭勃 等: "芳基高价碘的邻位炔丙基化和氰烷基化反应进展", 《浙江师范大学学报( 自然科学版)》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114773285A (en) * | 2022-03-25 | 2022-07-22 | 大连理工大学 | Efficient preparation method of alpha-amino oxazoline compound |
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