CN113135869B - Method for preparing alpha-aryl carbonyl compound and product - Google Patents

Method for preparing alpha-aryl carbonyl compound and product Download PDF

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CN113135869B
CN113135869B CN202010062704.7A CN202010062704A CN113135869B CN 113135869 B CN113135869 B CN 113135869B CN 202010062704 A CN202010062704 A CN 202010062704A CN 113135869 B CN113135869 B CN 113135869B
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CN113135869A (en
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李开笑
詹亚玲
李东阳
罗凡
田俊松
彭勃
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Zhejiang Normal University CJNU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
    • C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D263/06—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by oxygen atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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Abstract

The invention discloses a method for preparing an alpha-aryl carbonyl compound, which comprises the following steps: r1The substituted iodobenzene diacetate compound is activated by Lewis acid and then reacts with R2Reacting a substituted oxazoline compound in the presence of alkali to obtain the alpha-aryl carbonyl compound; the R is1Selected from H, one or more alkyl groups, one or more haloalkyl groups, alkoxycarbonyl groups, halogen, or polysubstitution of combinations of the foregoing atoms; r2Selected from H, alkyl, substituted alkyl, wherein the substituents are selected from cycloalkyl, halogen, alkoxy, heterocycloalkyl, substituted heterocycloalkyl, aryl, cyano, aryloxy, carbonyl. The method has mild reaction conditions, easy product separation and simple operation.

Description

Method for preparing alpha-aryl carbonyl compound and product
Technical Field
The invention belongs to the field of organic chemical synthesis, and particularly relates to a novel method for preparing an alpha-aryl carbonyl compound and a product.
Background
Due to the importance of α -arylcarbonyl compounds, extensive research has been undertaken. Are currently important intermediates in the synthesis of many pharmaceutically active molecules. The alpha-arylcarbonyl compounds are mainly used for the development of new drugs in the field of medicine.
Compounds containing an α -arylcarbonyl fragment have important pharmaceutical activities and physiology in the medical field. (J.org.chem.2001,66: 3653; J.Med.chem.1986,29: 523; J.Am.chem.Soc.1985,107: 435; J.Am.chem.Soc.1999,121: 2147.).
To date, several methods for the synthesis of α -arylcarbonyl compounds have been reported in succession.
The cyclic ketone compound can react with diaryl iodonium salt under the action of a metal reagent to prepare an alpha-aryl carbonyl compound (Tetrahedron Lett.1997,38: 5061; Organometallics 1997,16: 3241.). However, this type of reaction requires an equivalent amount of metal catalyst and uses a strong base, which is poor in functional group compatibility.
Carbonyl compounds and haloaromatics can also be used in the synthesis of alpha-arylcarbonyl compounds catalyzed by metallic palladium, nickel or copper (Angew. chem. int. Ed.1997,36: 1740; J.Am. chem.Soc.1997,119: 1110; J.Org. chem.2007,72: 5069; J.chem.Soc.1929, 1870.). However, the method has poor selectivity, narrow substrate range and poor functional group compatibility.
The [3,3] migration rearrangement reaction between aryl sulfoxide and 1, 3-dicarbonyl compound or nitrile compound can also be used for synthesizing alpha-aryl carbonyl compound (J.Am.chem.Soc.2011,133: 8510; J.Am.chem.Soc.2017,139: 4211). However, the method has special substrates and the reaction is sensitive to moisture.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a novel method for preparing an alpha-aryl carbonyl compound, which has the advantages of mild reaction conditions, easy product separation, simple operation and the like.
A method of making an α -arylcarbonyl compound, comprising: r1The substituted iodobenzene diacetate compound is activated by Lewis acid and then reacts with R2Reacting a substituted oxazoline compound in the presence of alkali to obtain the alpha-arylcarbonyl compound;
Figure BDA0002375003560000021
the R is1Selected from H, one or more alkyl groups, one or more haloalkyl groups, alkoxycarbonyl groups, halogen, or polysubstitution of combinations of the foregoing atoms; r2Selected from H, alkyl, substituted alkyl, wherein the substituents are selected from cycloalkyl, halogen, alkoxy, heterocycloalkyl, substituted heterocycloalkyl, aryl, cyano, aryloxy, carbonyl.
The present invention provides a novel method for preparing an alpha-arylcarbonyl compound by synthesizing the alpha-arylcarbonyl compound through [3,3] migratory rearrangement reaction of iodobenzene diacetate and oxazoline in the presence of an organic solvent.
Preferably, R is1Is selected from H, one or more C1-C3 alkyl, one or more halogenated C1-C3 alkyl, C1-C3 alkoxycarbonyl, halogen or polysubstitution formed by the combination of the atoms; r is2Is selected from H, C1-C10 alkyl and substituted C1-C10 alkyl, wherein the substituent is selected from cyclohexyl, halogen, C1-C3 alkoxy, piperidyl, substituted piperidyl, phenyl, halogen substituted phenyl, cyano, phenoxy, halogen substituted phenoxy, styrene substituted carbonyl and thiophene substituted carbonyl.
As a further preference, the R group1Selected from H, methyl, multiple methyl multiple substitutions, halogenated methyl, multiple halogenated methyl multiple substitutions, methoxycarbonyl, halogen or multiple substitutions consisting of halogen and one or more methyl; when the substituent is a poly-substituted substituent, it may be a meta-substituted substituent or a para-substituted substituent.
As a further preference, the R group2Selected from H, N-butyl, methyl, isopropyl substituted ethyl (substituted at the 1 or 2 position), isobutyl, isopropyl, cyclohexylmethyl, chloropropyl (substituted at the 1, 2, and 3 positions), bromo N-hexyl (optionally substituted at the 1 to 6 positions), I11 alkyl, 6- (p-toluenesulfonyloxy) hexyl, methoxy substituted N-hexyl (optionally substituted at the 1 to 6 positions), N-substituted piperidin-6-yl (such as N-p-toluenesulfonyl substituted) ethyl, 2-p-bromophenylethyl, cyano substituted pentyl, 4-p-chloromethyloxy N-butyl, 1-hepten-7-yl, 2-methoxycarbonylethyl and the like.
As an alternative, the α -arylcarbonyl compound is further hydrolyzed to give the corresponding carboxylic acid compound:
Figure BDA0002375003560000031
the compounds can be used to synthesize a variety of existing or new compounds. R1、R2The substitution is as described above.
The hydrolysis can be carried out in inorganic acid solution such as sulfuric acid, the reaction solvent can be 1, 4-dioxane, toluene and the like, and the reaction temperature can be 80-120 ℃.
Figure BDA0002375003560000032
The carboxylic acid compound may be further reduced to obtain a corresponding alcohol compound, or may be reacted with an alcohol compound or an ammonia compound to obtain a corresponding ester compound, amide compound, or the like. The iodine substituted position on the carboxylic acid compound can react with an alkene compound (such as styrene) or an alkyne compound (phenylacetylene) to obtain a corresponding phenylalkene compound (styrene substituted benzene carboxylic acid compound) or phenylalkyne compound (phenylacetylene substituted benzene carboxylic acid compound); or a biphenyl-substituted carboxylic acid compound with phenylboronic acid. Or the combination of the above reaction types is used for preparing the existing medicament or medicament intermediate, or preparing a new medicament or medicament intermediate and the like.
Preferably, the Lewis acid is one or more of trimethylsilyl trifluoromethanesulfonate, triethylsilyl trifluoromethanesulfonate and triisopropylsilyl trifluoromethanesulfonate.
Preferably, the reaction temperature is: -50 ℃ to 30 ℃; more preferably: -40 ℃ to 25 ℃. The reaction is carried out in an organic solvent, wherein the organic solvent is one or a mixture of dichloromethane and acetonitrile.
Preferably, the base used is one or more of 2-methylpyridine, triethylenediamine, triethylamine, diisopropylethylamine and 1, 8-diazabicycloundecen-7-ene.
Preferably, R is1Substituted iodobenzene diacetate compounds and R2The mol ratio of the substituted oxazoline compound is 1: (1-3); the R is1The molar ratio of the substituted iodobenzene diacetate compound to the Lewis acid is 1: (1-3); the R is1The molar ratio of the substituted iodobenzene diacetate compound to the alkali is 1: (1-3). That is, the equivalents of each species in the process are: r1Substituted iodobenzene diacetate 1.0equiv, R2Substituted oxazoline of 1.0 to 3.0equiv, LewisAcid 1.0 to 3.0equiv, base 1.0 to 3.0 equiv.
The specific process of the method comprises the following steps: r was weighed at-40 ℃ in a 100mL reaction flask1Adding solvent into substituted iodobenzene diacetate, adding Lewis acid, stirring, adding R2The substituted oxazoline is taken up, after a suitable time, the reaction progress is followed by thin layer chromatography, and the volume ratio of petroleum ether to ethyl acetate is (3/1) as a developing agent. After the reaction is finished, the reaction materials are decompressed and concentrated, and are separated by column chromatography to obtain the alpha-aryl carbonyl compound.
A compound having the structure shown in the formula:
Figure BDA0002375003560000041
the R is1Selected from H, one or more alkyl groups, one or more haloalkyl groups, alkoxycarbonyl groups, halogen, or polysubstitution of combinations of the foregoing atoms; r2Selected from H, alkyl, substituted alkyl, wherein the substituents are selected from cycloalkyl, halogen, alkoxy, heterocycloalkyl, substituted heterocycloalkyl, aryl, cyano, aryloxy, carbonyl.
A common structure is as follows:
Figure BDA0002375003560000051
a compound having the structure shown in the formula:
Figure BDA0002375003560000052
the R is1Selected from H, one or more alkyl groups, one or more haloalkyl groups, alkoxycarbonyl groups, halogen, or polysubstitution of combinations of the foregoing atoms; r2Selected from alkyl, substituted alkyl, wherein the substituents are selected from cycloalkyl, halogen, alkoxy, heterocycloalkyl, substituted heterocycloalkyl, aryl, cyano, aryloxy, carbonyl.
As a preferred scheme, the structure is shown as the following formula:
Figure BDA0002375003560000061
in the invention, R1Substituted iodobenzene diacetate compounds and R2The substituted oxazoline compound can be directly purchased in the market and can also be prepared by self.
Compared with the prior art, the method has the advantages that the method adopts R1Substituted iodobenzene diacetate and R2Substituted oxazoline [3,3]]The migration rearrangement reaction for synthesizing the alpha-aryl carbonyl compound has the advantages that:
the method has mild reaction conditions, good selectivity, easy product separation and simple operation;
the raw materials used in the method are cheap and easy to obtain, thus avoiding the catalyst which is used in the traditional method and is difficult to prepare and purchase, and the reaction condition is harsh;
the alpha-aryl carbonyl compound with stable chemical property can be prepared by the [3,3] migration rearrangement reaction of iodobenzene diacetate and oxazoline, and a new reaction strategy is provided for the synthesis of the compound.
Detailed Description
The following presents specific embodiments of the novel process for the preparation of α -arylcarbonyl compounds provided by the present invention, and a number of specific embodiments are provided. It should be noted that the practice of the present invention is not limited to the following practical examples.
Examples R1The substituted iodobenzene diacetate is prepared from a commercially available product R2The substituted oxazoline part is commercially available, and the preparation method of the partial compound comprises the following steps:
Figure BDA0002375003560000062
2-pentyl-4, 5-dihydrooxazole (4 a):
to 2-chloroethylamino hydrochloride (10.21g,88mmol) and Et at 0 deg.C3Hexanoyl chloride (11.2mL,80mmol) was added dropwise to a solution of N (28mL,200mmol) in DCM (267 mL). System liquid literThe mixture is warmed to room temperature and stirred for 3 hours. Quench the system with water, extract with DCM, Na2SO4Drying, concentration, recrystallization of the concentrate (DCM and PE) gave 9.67g of N- (2-chloroethyl) hexanamide as a white solid in 68% yield. (Rf: 0.48, eluent: PE/EtOAc: 1/1).
To a solution of N- (2-chloroethyl) hexanamide (9.67g,54mmol) in MeOH (360mL) was added NaOH (3.02g,76 mmol). Reflux overnight, concentrate, sat NaHCO3Diluting with water solution, and extracting with DCM. The organic layers were combined and Na2SO4Drying and concentrating. The residue was purified by column chromatography to give compound 4a as a pale yellow oil: 2-pentyl-4, 5-dihydrooxazole, 5.95g, yield 78%. (Rf 0.20, eluent: PE/EtOAc 3/1).1H NMR(600MHz,CDCl3):δ4.18(t,J＝9.5Hz,2H),3.78(t,J＝9.5Hz,2H),2.22(t,J＝7.7Hz,2H),1.66–1.54(m,2H),1.35–1.24(m,4H),0.86(t,J＝6.6Hz,3H)。
2- (4-methylpentyl) -4, 5-dihydrooxazole (4 e):
to a solution of 2-methyl-4, 5-dihydrooxazole (1.70g,20mmol) in THF (67mL) was added n-BuLi (2.5M,8.8mL) dropwise at-78 ℃. Stirring was carried out for 3h and a solution of 1-bromo-3-methylbutane (3.02g,20mmol) in THF (14.0mL) was added dropwise at-78 deg.C. Stirring is continued for 1h, and the system liquid is warmed to room temperature and stirred overnight. Adding water, extracting with DCM, mixing organic layers, and adding Na2SO4Drying, concentration and column chromatography of the residue afforded compound 4e, 2.30g, 74% yield. (Rf 0.25, eluent: PE/EtOAc 2/1).1H NMR(600MHz,CDCl3):δ4.21(t,J＝9.5Hz,2H),3.81(t,J＝9.5Hz,2H),2.26–2.21(m,2H),1.65–1.58(m,2H),1.58–1.51(m,1H),1.24–1.18(m,2H),0.87(d,J＝6.6Hz,6H)。
2- (2- (1-Ts-piperidin-4-yl) ethyl) -4, 5-dihydrooxazole (4 l):
according to the preparation of compound 4e, using 15mmol of the corresponding bromoalkyl group, the compound (4l) was obtained as a white solid m.p.134-136 ℃ in 2.37g, 47% yield. (Rf 0.33, eluent: PE/EtOAc 1/2).1H NMR(600MHz,CDCl3):δ7.60(d,J＝8.2Hz,2H),7.29(d,J＝8.0Hz,2H),4.16(t,J＝9.5Hz,2H),3.78–3.68(m,4H),2.40(s,3H),2.24–2.15(m,4H),1.75–1.67(m,2H),1.57–1.49(m,2H),1.31–1.15(m,3H)。
2- (7-methoxyheptyl) -4, 5-dihydrooxazole (4m):
following the preparation of compound 4e, using 8mmol of the corresponding bromoalkyl group, compound 4m was obtained as a yellow oil: 924.8mg, 58% yield (Rf 0.21, eluent: PE/EtOAc 1/1).1H NMR(600MHz,CDCl3):δ4.20(t,J＝9.5Hz,2H),3.80(t,J＝9.5Hz,2H),3.34(t,J＝6.6Hz,2H),3.31(s,3H),2.25(t,J＝7.7Hz,2H),1.65–1.58(m,2H),1.58–1.51(m,2H),1.38–1.28(m,6H)。
Other substrates may be prepared by similar methods as described above, or may be commercially available.
The preparation method comprises the following steps:
Figure BDA0002375003560000081
vacuumizing a 100ml reaction bottle, replacing nitrogen for three times, and adding R under the protection of nitrogen1Substituted iodobenzene diacetate (1.0mmol,1.0eq) and anhydrous DCM (10mL,0.1M) were placed at-40 ℃ and trimethylsilyl trifluoromethanesulfonate (2.0mmol,2.0eq.) was added after 10 minutes of reaction and R was added2The substituted oxazoline (2.0mmol,2.0eq.) was replaced and after a further 10 minutes, 2-methylpyridine (2.0mmol,2.0eq.) was added. After 24 hours the progress of the reaction was followed by thin layer chromatography using a volume ratio petroleum ether/ethyl acetate of 3/1 as developing agent, the reaction was monitored to be complete, treated with saturated sodium bicarbonate, extracted with DCM, the organic phases were combined and Na was added2SO4Drying, concentrating the organic phase under reduced pressure, and separating by column chromatography to obtain the product.
Example 1
R1Taking H, R2Taking n-butyl, 212.8mg of compound 1 was obtained as a yellow liquid in a yield of 62% according to the above-mentioned method.
1H NMR(600MHz,CDCl3):δ7.83(d,J＝7.9Hz,1H),7.38–7.34(m,1H),7.30(t,J＝7.5Hz,1H),6.95–6.88(m,1H),4.26–4.19(m,1H),4.19–4.13(m,1H),4.01(t,J＝7.5Hz,1H),3.85(t,J＝9.5Hz,2H),2.07–1.97(m,1H),1.83–1.74(m,1H),1.39–1.29(m,3H),1.25–1.18(m,1H),0.86(t,J＝7.2Hz,3H).
13C NMR(151MHz,CDCl3):δ169.1,143.2,139.7,128.8,128.7,127.9,101.8,67.4,54.4,48.9,34.0,29.6,22.7,14.0.
IR(neat):2954,2929,2871,1659,1583,1561,1460,1435,1171,1108,732.
HRMS(ESI-TOF):calculated for[C14H19INO(M+H+)]:344.0506,found:344.0508.
Example 2
R1Taking H, R2By the same procedure, 225.0mg of Compound 2 was obtained as a yellow liquid in a yield of 63% in the same manner as described above.
1H NMR(600MHz,CDCl3):δ7.86–7.82(m,1H),7.39–7.35(m,1H),7.33–7.29(m,1H),6.95–6.90(m,1H),4.26–4.14(m,2H),3.99(t,J＝7.5Hz,1H),3.90–3.80(m,2H),2.06–1.98(m,1H),1.84–1.76(m,1H),1.59–1.51(m,1H),1.32–1.23(m,1H),1.14–1.06(m,1H),0.88–0.83(m,6H).
13C NMR(151MHz,CDCl3):δ169.2,143.3,139.8,128.8,128.7,128.0,101.9,67.5,54.5,49.2,36.5,32.2,28.1,22.7,22.6.
IR(neat):2952,2901,2869,1660,1465,1435,1383,1365,1171,732.
HRMS(ESI-TOF):calculated for[C15H21INO(M+H+)]:358.0662,found:358.0662.
Example 3
R1Taking H, R2The same procedure as described above gave 210.8mg of Compound 3 as a white solid, in 55% yield, of cyclohexylmethyl group. 1H NMR (600MHz, CDCl3): delta 7.88-7.80 (m,1H), 7.41-7.37 (m,1H), 7.33-7.28 (m,1H), 6.96-6.89 (m,1H), 4.26-4.20 (m,1H), 4.19-4.12 (m,2H), 3.89-3.79 (m,2H), 1.96-1.89 (m,1H), 1.84-1.74 (m,2H), 1.70-1.58 (m,4H), 1.28-1.12 (m,4H), 1.00-0.89 (m,2H).
13C NMR(151MHz,CDCl3):δ169.3,143.6,139.9,128.8,128.7,128.1,101.6,67.4,54.5,46.3,42.0,35.3,33.7,33.4,26.6,26.3,26.2.
IR(neat):2921,2886,2849,2836,1665,1464,1446,1180,765.
HRMS(ESI-TOF):calculated for[C17H23INO(M+H+)]:384.0819,found:384.0813.
Example 4
R1Taking H, R2Using the same procedure, 196.3mg of compound 4 was obtained as a yellow liquid in a yield of 60%. 1H NMR (600MHz, CDCl3): δ 7.85-7.80 (m,1H), 7.35-7.32 (m,1H), 7.32-7.28 (m,1H), 6.96-6.87 (m,1H), 4.25-4.19 (m,1H), 4.19-4.12 (m,1H),4.03(t, J ═ 7.3Hz,1H),3.84(t, J ═ 9.7Hz,2H),3.51(t, J ═ 6.5Hz,2H), 2.20-2.12 (m,1H), 1.98-1.84 (m,2H), 1.76-1.68 (m,1H).
13C NMR(151MHz,CDCl3):δ168.5,142.5,139.8,129.0,128.8,127.8,101.6,67.5,54.4,48.2,44.7,31.5,30.4.
IR(neat):2954,2879,1659,1583,1562,1464,1434,1010,750,728.
HRMS(ESI-TOF):calculated for[C13H16ClINO(M+H+)]:363.9960,found:363.9958.
Example 5
R1Taking H, R2By the same procedure, 240.8mg of compound 5 was obtained as a yellow liquid in a yield of 60% using 6-methoxyhexyl.
1H NMR(600MHz,CDCl3):δ7.85–7.81(m,1H),7.37–7.33(m,1H),7.32–7.28(m,1H),6.94–6.90(m,1H),4.25–4.19(m,1H),4.19–4.13(m,1H),4.01(t,J＝7.5Hz,1H),3.88–3.81(m,2H),3.34–3.31(m,2H),3.30(s,3H),2.06–1.98(m,1H),1.82–1.74(m,1H),1.55–1.50(m,2H),1.39–1.25(m,6H).
13C NMR(151MHz,CDCl3):δ169.1,143.2,139.8,128.8,128.7,128.0,101.8,73.0,67.4,58.6,54.5,48.9,34.2,29.7,29.4,27.4,26.0.
IR(neat):2928,2855,1660,1463,1435,1115,1010,982,729.
HRMS(ESI-TOF):calculated for[C17H25INO2(M+H+)]:402.0924,found:402.0912。
Example 6
R1Taking H, R2Taking N-Ts piperidin-1-yl-methyl group, 323.0mg of compound 6 as a yellow liquid was obtained in the same manner, and the yield was 60%.1H NMR(600MHz,CDCl3):δ7.60–7.72(m,1H),7.58–7.52(m,2H),7.29–7.26(m,1H),7.26–7.21(m,3H),6.88–6.82(m,1H),4.16–4.10(m,1H),4.09–4.00(m,2H),3.75(t,J＝9.5Hz,2H),3.68(d,J＝11.5Hz,2H),2.35(s,3H),2.17–2.09(m,2H),1.94–1.87(m,1H),1.81(d,J＝12.7Hz,1H),1.73(d,J＝12.8Hz,1H),1.64–1.58(m,1H),1.38–1.23(m,2H),1.21–1.16(m,1H).
13C NMR(151MHz,CDCl3):δ168.6,143.4,142.7,139.8,133.1,129.6,129.0,128.8,127.8,127.7,101.4,67.4,54.3,46.3,46.2,46.0,40.4,32.7,31.7,31.4,21.5.
IR(neat):2917,2843,1658,1596,1435,1194,1144,1094,814.
HRMS(ESI-TOF):calculated for[C23H28IN2O3S(M+H+)]:539.0860,found:539.0830.
Example 7
R1Taking methyl (I-substituted para), R2Taking n-butyl, 235.8mg of Compound 7 was obtained as a yellow liquid in a yield of 66% by the same method.
1H NMR(600MHz,CDCl3):δ7.69(d,J＝8.1Hz,1H),7.17–7.14(m,1H),6.78–6.73(m,1H),4.27–4.14(m,2H),3.97(t,J＝7.5Hz,1H),3.90–3.82(m,2H),2.28(s,3H),2.07–1.96(m,1H),1.82–1.73(m,1H),1.39–1.30(m,3H),1.25–1.19(m,1H),0.87(t,J＝7.2Hz,3H).
13C NMR(151MHz,CDCl3):δ169.4,142.9,139.4,138.7,130.0,128.6,97.8,67.5,54.4,48.7,34.1,29.6,22.8,21.2,14.1.
IR(neat):2954,2928,2871,1159,1466,1171,1008,984,806,731.
HRMS(ESI-TOF):calculated for[C15H21INO(M+H+)]:358.0662,found:358.0656.
Example 8
R1Taking Cl (I substituted pairBit), R2Taking n-butyl, 151.1mg of compound 8 as a yellow liquid was obtained in the same manner, and the yield was 40%.
1H NMR(400MHz,CDCl3):δ7.73(d,J＝8.4Hz,1H),7.35(d,J＝2.5Hz,1H),6.94–6.89(m,1H),4.27–4.15(m,2H),3.96(t,J＝7.5Hz,1H),3.86(t,J＝9.6Hz,2H),2.05–1.96(m,1H),1.78–1.71(m,1H),1.37–1.28(m,3H),1.25–1.19(m,1H),0.87(t,J＝7.2Hz,3H).
13C NMR(101MHz,CDCl3):δ168.4,145.2,140.6,135.0,129.0,128.1,98.7,67.5,54.5,48.9,34.0,29.5,22.6,14.0.
IR(neat):2953,2927,2870,1656,1575,1478,1455,1193,1105,732.
HRMS(ESI-TOF):calculated for[C14H18ClINO(M+H+)]:378.0116,found:378.0104.
Example 9
R1Taking H, R2Taking the methyl group, 225.8mg of a yellow liquid compound, 9, 2- (1- (2-iodophenyl) ethyl) -4, 5-dihydrooxazole, 75% yield, (Rf ═ 0.20, element: PE/EtOAc ═ 3/1) was obtained in the same manner.
1H NMR(600MHz,CDCl3):δ7.83(d,J＝7.9Hz,1H),7.30(d,J＝4.0Hz,2H),6.96–6.88(m,1H),4.28–4.15(m,2H),4.13–4.04(m,1H),3.92–3.81(m,2H),1.48(d,J＝7.1Hz,3H).
13C NMR(151MHz,CDCl3):δ169.8,144.3,139.8,128.80,128.79,127.5,100.8,67.7,54.5,43.7,19.2.
IR(neat):2975,2932,2901,2878,1659,1584,1466,1433,1181,1118,747.
HRMS(ESI-TOF):calculated for[C11H13INO(M+H+)]:302.0036,found:302.0030。
Example 10
R1Taking H, R2Taking H, 89mg of yellow liquid compound 10 can be obtained by the same method: 2- (2-iodophenyl) -4, 5-dihydrooxazole, 31% yield (Rf ═ 0.33, eluent: PE/EtOAc ═ 1/1).
1H NMR(600MHz,CDCl3):δ7.86–7.81(m,1H),7.36–7.28(m,2H),6.97–6.92(m,1H),4.26(t,J＝9.5Hz,2H),3.84(t,J＝9.5Hz,2H),3.75(s,2H).
13C NMR(151MHz,CDCl3):δ166.0,139.7,138.6,130.2,128.9,128.5,100.9,67.8,54.7,39.8.
IR(neat):2902,2878,1662,1585,1563,1464,1206,1107,733.
HRMS(ESI-TOF):calculated for[C10H11INO(M+H+)]:287.9880,found:287.9879。
Preparation of carboxylic acid:
Figure BDA0002375003560000121
obtaining a corresponding carboxylic acid compound from the compound 1-10 according to the following method:
to a 25mL reaction tube was added compound I (1.0mmol), 4M H2SO4(2.0mL) and 1, 4-dioxane (2.0mL), followed by reaction at 100 ℃ for 15 h. After the reaction was completed, it was cooled to room temperature, and 2M NaOH was added thereto to make it alkaline, followed by concentration under reduced pressure. The residue is acidified with 1M HCl and extracted with dichloromethane, and the organic phase is freed from anhydrous Na2SO4Drying and concentrating under reduced pressure to obtain the product, which does not need further purification.
For compounds 1, 9, 10, the corresponding carboxylic acid products are:
Figure BDA0002375003560000131
Figure BDA0002375003560000132
and the like, these compounds can be synthesized into various compounds (e.g., alcohol compounds, styrene-substituted benzene carboxylic acid compounds, biphenyl carboxylic acid compounds).

Claims (3)

1. A method of preparing an α -arylcarbonyl compound, comprising: r1The substituted iodobenzene diacetate compound is activated by Lewis acid and then reacts with R2Substituted oxazoline compounds in the presence of a baseReacting under the condition to obtain the alpha-aryl carbonyl compound;
Figure FDA0003544745770000011
the R is1Is selected from H, one or more C1-C3 alkyl, one or more halogenated C1-C3 alkyl, halogen or polysubstitution formed by the combination of the substituents;
R2selected from H, C1-C10 alkyl and substituted C1-C10 alkyl, wherein the substituent is selected from cyclohexyl, halogen, C1-C3 alkoxy and piperidyl;
the Lewis acid is one or more of trimethylsilyl trifluoromethanesulfonate, triethylsilyl trifluoromethanesulfonate and triisopropylsilyl trifluoromethanesulfonate;
the reaction temperature is as follows: -50 ℃ to 30 ℃; the reaction is carried out in an organic solvent, wherein the organic solvent is one or a mixture of dichloromethane and acetonitrile;
the base used is one or more of 2-methylpyridine, triethylenediamine, triethylamine, diisopropylethylamine and 1, 8-diazabicycloundecen-7-ene.
2. A process according to claim 1, wherein the α -arylcarbonyl compound is further hydrolyzed to give the corresponding carboxylic acid compound:
Figure FDA0003544745770000012
3. the method for producing an α -arylcarbonyl compound according to claim 1, wherein R is1Substituted iodobenzene diacetate compounds and R2The mol ratio of the substituted oxazoline compound is 1: (1-3); the R is1The molar ratio of the substituted iodobenzene diacetate compound to the Lewis acid is 1: (1-3); the R is1Iodobenzene reaction of substituted diacetic acidThe molar ratio of compound to base is 1: (1-3).
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