CN117820249A - 2-oxazoline compound and preparation method thereof - Google Patents

2-oxazoline compound and preparation method thereof Download PDF

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CN117820249A
CN117820249A CN202410026211.6A CN202410026211A CN117820249A CN 117820249 A CN117820249 A CN 117820249A CN 202410026211 A CN202410026211 A CN 202410026211A CN 117820249 A CN117820249 A CN 117820249A
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oxazolidin
ethynyl
oxazoline compound
hydrogen gas
reaction
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何广科
叶星缘
李秋文
肖含
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Nanjing Tech University
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Nanjing Tech University
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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
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D263/12—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with radicals containing only hydrogen and carbon atoms
    • 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
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
    • C07J1/0051—Estrane derivatives
    • C07J1/0059—Estrane derivatives substituted in position 17 by a keto group

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

The invention discloses a preparation method of a 2-oxazoline compound. The method takes methanol, ethanol and dimethyl sulfoxide as solvents, and adds alkali at the temperature of 0-100 ℃ for 2-10 hours, then adds water for quenching, and carries out vacuum concentration to obtain the 2-oxazoline compound with the yield of 74-99%. The invention realizes the preparation of N-alkynyl oxazolidine-2-ketone alkynylamide for the first time (structural formula is:) The 2-oxazoline compound (structural formula:) Is prepared in green with high efficiency; the reaction operation is simple and convenient, the yield is high, the application range of the substrate is wide, and the 2-oxazoline compound can be synthesized in gram scale; the method also has the advantages that the product does not need column chromatography separation, a large amount of reaction solvent can be recovered, the production cost is reduced, and the like. The method is adopted to modify the natural product estrone molecule with biological activity to obtain the 2-oxazoline compound 1 with the estrone methylene substitution. And (3) injection: the attached drawing of the abstract is a nuclear magnetic resonance carbon spectrum of an estrone methylene substituted 2-oxazoline compound 1 in the embodiment of the invention.

Description

2-oxazoline compound and preparation method thereof
Technical Field
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a 2-oxazoline compound and a preparation method thereof.
Background
The 2-oxazoline compound is a valuable organic synthesis intermediate in an organic synthesis path, and the derivative thereof can be widely applied to the preparation of industrial-grade medicaments such as chloramphenicol, thiamphenicol, fluomycin and the like. In addition, chiral oxazolines and bisoxazolines may also be widely present as ligands in asymmetric catalysis. The synthesis method of the 2-oxazoline compound is growing due to important application of the 2-oxazoline compound in the fields of medicine, biology, industry and the like. Therefore, the research on 2-oxazoline heterocyclic compounds, a preparation method and application thereof is very focused.
In 2011, the Chen Huiying subject group adopted PPh 3 DDQ is a dehydration and activation reagent, and under neutral conditions, 2-oxazoline compounds and 2-benzoxazole compounds are synthesized by taking acylamino alcohol and acyl phenol as raw materials respectively, and the yield is 44-99% (Xu, Q.; li, Z.; chen, H.Chin.J.Chem.2011, 29, 925-932).
In 2012, the Pathak group synthesized N- (β -hydroxyethyl) sulfonamide rings using deamination of the sulfonamide with 2-aminoethanol, followed by dehydrosulfidation under alkaline conditions, a mild and efficient synthesis of 2-oxazolines in yields of 35-87% (Goud, d.; pathak, u. Synthesis 2012, 44, 3678-3682).
In 2016, the Orelli group adopted polyphosphoric acid (PPA) ester/chloroform system, and the microwave assisted omega-amidol cyclizing at 90 ℃ generated 5-7 membered ring 2-oxazoline compound, the reaction was efficient, the yield was medium to good (Mollo, M.; orelli, L.org. Lett.2016, 18, 6116-6119).
In summary, although there are many synthetic methods related to the synthesis of 2-oxazolines, there is no report in the literature about the synthesis of 2-oxazolines heterocyclic compounds using N-alkynyl oxazolidin-2-one alkynylamides as raw materials. Therefore, from the standpoint of environmental protection and economy, the method for developing the efficient synthesis of the 2-oxazoline heterocyclic compound by adopting the cheap and easily available N-alkynyl oxazolidine-2-ketone alkynamide as the raw material is very attractive.
Disclosure of Invention
Firstly, the invention aims to provide a preparation method of 2-oxazoline compounds, which aims to solve the problem that the prior literature does not relate to the synthesis of 2-oxazoline compounds by using N-alkynyl oxazolidine-2-ketone alkynylamide as a raw material; secondly, the invention aims to provide the 2-oxazoline compound obtained by the preparation method; finally, the invention aims to provide the application of the 2-oxazoline compound.
The invention is realized in such a way that a preparation method of a 2-oxazoline compound comprises the following steps:
(1) Sequentially adding alkali and alkynylamide into a reaction solvent, and stirring and reacting for 2-10 hours at the temperature of 0-100 ℃ to obtain a reaction solution; wherein, the molar volume ratio of the alkynylamide to the alkali to the reaction solvent is (0.2-0.4) mmol to (0.2-0.8) mmol to (2-6) mL respectively;
(2) And removing the reaction solvent in the reaction liquid to obtain the 2-oxazoline compound.
Preferably, in step (1), the base is any one of potassium bicarbonate, sodium bicarbonate, potassium phosphate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, and diethylamine.
Preferably, in the step (1), the alkynylamide is an N-alkynyloxazolidine-2-one compound with a structural formula of
Preferably, the alkynylamide is selected from any one of table 1.
TABLE 1
Alkynylamides R 1 Representative group R 2 Representative group Chemical name of the starting alkynylamide
1 4-fluorophenyl group Hydrogen gas 3- ((4-fluorophenyl) ethynyl) oxazolidin-2-one
2 4-chlorophenyl group Hydrogen gas 3- ((4-chlorophenyl) ethynyl) oxazolidin-2-one
3 4-bromophenyl group Hydrogen gas 3- ((4-bromophenyl) ethynyl) oxazolidin-2-one
4 2-methylphenyl radical Hydrogen gas 3- ((2-methylphenyl) ethynyl) oxazolidin-2-one
5 3-methylphenyl radical Hydrogen gas 3- ((3-methylphenyl) ethynyl) oxazolidin-2-one
6 4-methylphenyl radical Hydrogen gas 3- ((4-methylphenyl) ethynyl) oxazolidin-2-one
7 4-trifluoromethylphenyl group Hydrogen gas 3- ((4-trifluoromethylphenyl) ethynyl) oxazolidin-2-one
8 4-nitrophenyl group Hydrogen gas 3- ((4-nitrophenyl) ethynyl) oxazolidin-2-one
9 2-naphthyl radical Hydrogen gas 3- ((1-naphthyl) ethynyl) oxazolidin-2-one
10 3-pyridyl group Hydrogen gas 3- ((3-pyridinyl) ethynyl) oxazolidin-2-one
11 1-cyclohexenyl Hydrogen gas 3- ((1-cyclohexylenyl) ethynyl) oxazolidin-2-one
12 Triisopropyl (III)Silicon-based Hydrogen gas 3- ((triisopropylsilyl) ethynyl) oxazolidin-2-one
13 Estrononyl group Hydrogen gas Estrone ethynyl oxazolidin-2-ones
Preferably, in step (1), the reaction solvent is selected from any one of methanol, ethanol and dimethyl sulfoxide. Preferably, the reaction solvent is methanol.
Preferably, in step (1), the reaction temperature is any temperature of 0 to 100 ℃. Preferably, the reaction temperature is 25 ℃.
The invention further provides the 2-oxazoline compound obtained by the preparation method.
The invention further discloses that the above steps can be used to prepare estrone methylene substituted 2-oxazoline compounds having biologically active fragments.
The method of the invention has the following advantages:
(1) The method adopts the convenient and easily available alkynylamide as the raw material, the raw material can be obtained through commercial paths or is obtained by coupling reaction of alkyne bromine and corresponding amide through carbon-nitrogen bond, and the obtaining cost is low; and the reaction is applicable to a wide range of substrates, such as various aryl and alkyl substituted alkynylamides;
(2) The method adopts a solvent which is low in cost, stable and easy to store as a reaction solvent, and can be largely recovered;
(3) The method adopts common alkali and has low cost; the reaction condition is mild, and high temperature and high pressure are not needed;
the invention adopts the estrone ethynyl substituted oxazolidine-2-ketone as the raw material, can be used for preparing the estrone methylene substituted 2-oxazoline compound 1, and can be used as a potential bioactive molecule.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of 2- (2-methylbenzyl) -4, 5-dihydro-oxazole;
FIG. 2 is a nuclear magnetic resonance carbon spectrum of 2- (2-methylbenzyl) -4, 5-dihydro-oxazole;
FIG. 3 is a nuclear magnetic resonance carbon spectrum of estrone methylene substituted 2-oxazoline compound 1.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1
(1) To a 10mL Schlenk tube, 0.4mmol 3- ((2-methylphenyl) ethynyl) oxazolidin-2-one, 0.8mmol cesium carbonate and 6mL dimethyl sulfoxide were added, and the reaction was stirred at room temperature, wherein the reaction equation was:
(2) After completion of the reaction by TLC, the solvent was removed by vacuum rotary evaporator and the product was 2- (2-methylbenzyl) -4, 5-dihydrooxazole as a colorless transparent oily liquid in 87% yield. 1 H NMR(400MHz，CDCl 3 )δ6.97-7.39(m，4H)，4.21(t，J＝9.5Hz，2H)，3.82(t，J＝9.5Hz，2H)，3.60(s，2H)，2.35(s，3H). 13 C NMR(100MHz，CDCl 3 )δ166.6，136.6，133.6，120.2，129.7，127.2，126.0，67.4，54.3，32.3，19.5。
Example 2
(1) This example is essentially the same as example 1 above, except that the alkynylamide is 3- ((4-fluorophenyl) ethynyl) oxazolidin-2-one, 0.2mmol of 3- ((4-fluorophenyl) ethynyl) oxazolidin-2-one, 0.6mmol of sodium bicarbonate are added to a 10mL schlenk tube, 3mL of ethanol are added and the reaction is stirred at room temperature, equation:
(2) After the completion of the reaction by TLC, the solvent was removed by vacuum rotary evaporator, and the product was colorless transparent oily liquid 2- (4-fluorobenzyl) -4, 5-dihydrooxazole in 88% yield. 1 H NMR(400MHz，CDCl 3 )δ7.58(d，J＝8.0Hz，2H)，7.43(d，J＝8.0Hz，2H)，4.25(t，J＝9.5Hz，2H)，3.82(t，J＝9.5Hz，2H)，3.67(s，2H). 13 C NMR(100MHz，CDCl 3 )δ166.8，162.5(d，J＝243.6Hz)，130.8(d，J＝3.4Hz)，130.5(d，J＝8.0Hz)，130.3(d，J＝21.4Hz)，67.6，54.4，33.8. 19 F NMR(376MHz，CDCl 3 )δ-62.5。
Example 3
(1) This example is essentially the same as example 1 above, except that the alkynylamide is 3- ((4-trifluoromethylphenyl) ethynyl) oxazolidin-2-one, 0.4mmol sodium carbonate, and 4mL methanol are added to a 10mL Schlenk tube, and the reaction is stirred at 80deg.C, as follows:
(2) After completion of the reaction by TLC, the solvent was removed by vacuum rotary evaporator and the product was 2- (4-trifluoromethylbenzyl) -4, 5-dihydrooxazole as a colorless transparent oily liquid in 84% yield. 1 H NMR(400MHz，CDCl 3 ，ppm)：δ7.19-7.36(m，2H)，6.87-7.13(m，2H)，4.24(t，J＝9.5Hz，1H)，3.84(t，J＝9.5Hz，1H)，3.58(s，2H). 13 C NMR(100MHz，CDCl 3 )δ166.1，139.1，129.30(q，J＝32.3Hz)，129.37，125.5(q，J＝3.8Hz)，124.1(q，J＝270.4Hz)，67.7，54.4，34.4. 19 F NMR(376MHz，CDCl 3 )δ-62.5。
Example 4
(1) This example is essentially the same as example 1 above, except that the alkynylamide is 3- ((1-naphthyl) ethynyl) oxazolidin-2-one, 0.4mmol 3- ((1-naphthyl) ethynyl) oxazolidin-2-one, 0.6mmol potassium bicarbonate are added to a 10mL schlenk tube, 4mL dimethyl sulfoxide is added and the reaction is stirred at 80 ℃ as follows:
(2) After completion of the reaction by TLC, the solvent was removed by vacuum rotary evaporator and the product was 2- ((1-naphthyl) methyl) -4, 5-dihydrooxazole as a colorless transparent oily liquid in 99% yield. 1 H NMR(400MHz，CDCl 3 ，ppm)：δ8.12(d，J＝8.4Hz，1H)，7.85(d，J＝7.9Hz，1H)，7.75-7.82(m，1H)，7.40-7.57(m，4H)，4.20(t，J＝9.5Hz，1H)，4.06(s，2H)，3.83(t，J＝9.5Hz，1H)； 13 C NMR(100MHz，CDCl 3 )δ166.7，133.7，131.9，131.3，128.5，127.8，127.5，126.1，125.6，125.4，123.8，67.5，54.3，32.3。
Example 5
(1) This example is essentially the same as example 1 above, except that the alkynylamide is 3- ((1-cyclohexenyl) ethynyl) oxazolidin-2-one, 0.2mmol 3- ((1-cyclohexenyl) ethynyl) oxazolidin-2-one, 0.6mmol potassium hydroxide, and 3mL methanol are added to a 10mL schlenk tube, and the reaction is stirred at 80 ℃ as follows:
(2) After the reaction was complete by TLC, the solvent was removed by vacuum rotary evaporator and the product was colorless transparent oily liquid 2- ((1-cyclohexenyl) methyl) -4, 5-dihydrooxazole in 87% yield. 1 H NMR(400MHz，CDCl 3 )δ5.47-5.69(m，1H)，4.24(t，J＝9.5Hz，2H)，3.84(t，J＝9.4Hz，2H)，2.94(s，2H)，1.94-1.98(m，4H)，1.51-1.69(m，4H)； 13 C NMR(100MHz，CDCl 3 )δ166.8，131.9，124.7，67.2，54.3，36.8，28.0，25.1，22.6，21.9。
Example 6
(1) This example is essentially the same as example 1 above, except that the alkynylamide is 3- ((3-pyridinyl) ethynyl) oxazolidin-2-one, 0.3mmol 3- ((3-pyridinyl) ethynyl) oxazolidin-2-one, 0.6mmol potassium phosphate are added to a 10mL schlenk tube, 3mL ethanol is added and the reaction is stirred at 80 ℃ as follows:
(2) After completion of the reaction by TLC, the solvent was removed by vacuum rotary evaporator and the product was 2- ((1-cyclohexyl) methyl) -4, 5-dihydrooxazole as a colorless transparent oily liquid in 94% yield. 1 H NMR(400MHz，CDCl 3 )δ8.55(d，J＝2.3Hz，1H)，8.48-8.53(dd，J 1 ＝4.8Hz，J 2 ＝1.7Hz，1H)，7.58-7.74(dt，J 1 ＝7.8Hz，J 2 ＝2.0Hz，1H)，7.20-7.29(ddd，J 1 ＝7.8Hz，J 2 ＝4.9Hz，J 3 ＝0.9Hz，1H)，4.21-4.31(m，2H)，3.85(t，J＝9.5Hz，2H)，3.62(s，2H). 13 C NMR(100MHz，CDCl 3 )δ166.0，150.1，148.3，136.5，130.8，123.4，67.7，54.4，31.9.
Example 7
(1) This example is essentially the same as example 1 above, except that the alkynylamide is 3- ((triisopropylsilyl) ethynyl) oxazolidin-2-one, 0.3mmol 3- ((triisopropylsilyl) ethynyl) oxazolidin-2-one, 0.6mmol diethylamine, and 3mL methanol are added to a 10mL schlenk tube, and the reaction is stirred at 50 ℃ as follows:
(2) After completion of the TLC monitoring the reaction, the solvent was removed by vacuum rotary evaporator and the product was 2- ((1-triisopropylsilyl) methylketone as a colorless transparent oily liquidPhenyl) -4, 5-dihydro oxazole in 97% yield. 1 H NMR(400MHz，CDCl 3 )δ4.16(t，J＝9.4Hz，2H)，3.77(t，J＝9.5Hz，2H)，1.82(s，2H)，1.02-1.89(m，21H). 13 C NMR(100MHz，CDCl 3 )δ168.1，66.9，54.4，18.3，11.1，10.9。
Example 8
(1) This example is essentially the same as example 1 above, except that the alkynylamide is 3- ((4-nitrophenyl) ethynyl) oxazolidin-2-one, 0.4mmol 3- ((4-nitrophenyl) ethynyl) oxazolidin-2-one, 0.6mmol sodium hydroxide are added to a 10mL schlenk tube, 4mL ethanol is added and the reaction is stirred at 50 ℃ as follows:
(2) After completion of the reaction by TLC, the solvent was removed by vacuum rotary evaporator and the product was 2- (4-nitrobenzyl) -4, 5-dihydrooxazole as a colorless transparent oily liquid in 74% yield. 1 H NMR(400MHz，CDCl 3 )δ8.08-8.29(m，2H)，7.39-7.60(m，2H)，4.28(t，J＝9.5Hz，2H)，3.87(t，J＝9.5Hz，2H)，3.72(s，2H). 13 C NMR(100MHz，CDCl 3 )δ165.4，147.0，142.6，129.9，123.7，67.7，54.4，34.3。
Example 9
(1) The embodiment is the application of the 2-oxazoline compound in synthesis, and can be used for modifying the biological macromolecular structure with activity. To a 10mL Schlenk tube, 0.2mmol of estrone ethynyl substituted oxazolidin-2-one and 0.8mmol of potassium carbonate were added, 4mL of dimethyl sulfoxide was added, and the reaction was stirred at 50℃to give the following reaction equation:
(2) TLC (developing agent is petroleum ether/ethyl acetate) monitoring reaction completely, vacuum concentrating to remove solvent to obtain estrone methylene substituted 2-oxazolineCompound 1, as a pale yellow liquid, yield 94%. 1 H NMR(400MHz，CDCl 3 )δ7.25(d，J＝8.5Hz，1H)，7.09(d，J＝8.0Hz，1H)，7.03(s，1H)，4.23(t，J＝9.5Hz，2H)，3.83(t，J＝9.5Hz，2H)，3.58(s，2H)，2.86-2.99(dd，J 1 ＝8.9Hz，J 2 ＝4.2Hz，2H)，2.45-2.53(dd，J 1 ＝18.7Hz，J 2 ＝8.6Hz，1H)，2.38-2.44(m，1H)，2.24-2.32(m，1H)，1.91-2.20(m，4H)，1.36-1.72(m，6H)，0.90(s，3H). 13 C NMR(100MHz，CDCl 3 )δ220.8，167.1，138.3，136.6，132.4，129.5，126.3，125.5，67.5，54.3，50.3，47.8，44.1，37.9，35.7，34.1，31.4，29.2，26.3，25.5，21.4，13.7。

Claims (8)

1. The preparation method of the 2-oxazoline compound is characterized by comprising the following steps of:
(1) Sequentially adding alkali and alkynylamide into a reaction solvent, and stirring and reacting for 2-10 hours at the temperature of 0-100 ℃ to obtain a reaction solution; wherein, the molar volume ratio of the alkynylamide to the alkali to the reaction solvent is (0.2-0.4) mmol to (0.2-0.8) mmol to (2-6) mL respectively;
(2) Removing the reaction solvent in the reaction solution to obtain the 2-oxazoline compound with the structural formula ofThe alkali is selected from potassium bicarbonate, sodium bicarbonate, potassium phosphate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide and diethylamine, and the alkynylamide is N-alkynyl oxazolidin-2-one molecule with a structural formula of->Selected from any one of table 1. R in the raw material alkynylamide molecule 1 And R is 2 Representative groups and R in 2-oxazoline compound molecules of the product 1 And R is 2 Representative groups are in one-to-one correspondence.
TABLE 1
Alkynylamides R 1 Representative group R 2 Representative group Chemical name of the starting alkynylamide 1 4-fluorophenyl group Hydrogen gas 3- ((4-fluorophenyl) ethynyl) oxazolidin-2-one 2 4-chlorophenyl group Hydrogen gas 3- ((4-chlorophenyl) ethynyl) oxazolidin-2-one 3 4-bromophenyl group Hydrogen gas 3- ((4-bromophenyl) ethynyl) oxazolidin-2-one 4 2-methylphenyl radical Hydrogen gas 3- ((2-methylphenyl) ethynyl) oxazolidin-2-one 5 3-methylphenyl radical Hydrogen gas 3- ((3-methylphenyl) ethynyl) oxazolidin-2-one 6 4-methylphenyl radical Hydrogen gas 3- ((4-methylphenyl) ethynyl) oxazolidin-2-one 7 4-trifluoromethylphenyl group Hydrogen gas 3- ((4-trifluoromethylphenyl) ethynyl) oxazolidin-2-one 8 4-nitrophenyl group Hydrogen gas 3- ((4-nitrophenyl) ethynyl) oxazolidin-2-one 9 2-naphthyl radical Hydrogen gas 3- ((1-naphthyl) ethynyl) oxazolidin-2-one 10 3-pyridyl group Hydrogen gas 3- ((3-pyridinyl) ethynyl) oxazolidin-2-one 11 1-cyclohexenyl Hydrogen gas 3- ((1-cyclohexylenyl) ethynyl) oxazolidin-2-one 12 Triisopropyl silicon base Hydrogen gas 3- ((triisopropylsilyl) ethynyl) oxazolidin-2-one 13 Estrononyl group Hydrogen gas Estrone ethynyl oxazolidin-2-ones
。
Note that: estrone group as
2. The method for producing a 2-oxazoline compound according to claim 1, wherein in the step (1), the base comprises any one of potassium hydrogencarbonate, sodium hydrogencarbonate, potassium phosphate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, diethylamine.
3. The method for producing 2-oxazoline compound according to claim 2, wherein the base is potassium carbonate.
4. The method for producing a 2-oxazoline compound according to claim 1, wherein in the step (1), the reaction solvent is selected from any one of methanol, ethanol and dimethyl sulfoxide.
5. The method for producing 2-oxazoline compound according to claim 4, wherein the reaction solvent is methanol.
6. The method for producing a 2-oxazoline compound according to claim 1, wherein in the step (1), the reaction temperature is any temperature of 0 to 100 ℃.
7. The method for producing a 2-oxazoline compound according to claim 6, wherein the reaction temperature is 25 ℃.
8. The 2-oxazoline heterocyclic compound obtained by the production method according to any one of claims 1 to 7.
CN202410026211.6A 2024-01-08 2024-01-08 2-oxazoline compound and preparation method thereof Pending CN117820249A (en)

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