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1, 3, 4-oxadiazole ethyl acetate and synthesis method thereof
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A technology of ethyl oxadiazole acetate and synthesis method, applied in 1 field, can solve problems such as preparing
Pending Publication Date: 2022-08-02
TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE
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Problems solved by technology
Therefore, some substrates containing sensitive functional groups are difficult to prepare the corresponding 1,3,4-oxadiazole acetate by this method
Method used
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Embodiment 1
[0015] Example 1: Ethyl 5-phenyl-1,3,4-oxadiazole-2-acetate (Compound 1)
[0016]
[0017] In a dry sealed tube (15 mL) were added benzohydrazide (0.50 mmol), ethyl 3,3,3-trifluoropropionate (0.55 mmol), Na 2 CO 3 (0.75 mmol) and absolute ethanol (5 mL). The resulting mixture was then heated at 80°C until complete consumption of the starting material was monitored by TLC or GC-MS analysis. After cooling, the reaction solution was filtered through celite and washed with ethyl acetate. The obtained mixture was concentrated under reduced pressure and purified by silica gel column to obtain Compound 1 (110 mg, 95%). 1 H NMR (500MHz, CDCl 3 )δ8.08-8.00(m, 2H), 7.59-7.45(m, 3H), 4.24(q, J=7.1Hz, 2H), 4.03(s, 2H), 1.29(t, J=7.1Hz, 3H) ); 13 C NMR (125MHz, CDCl 3 )δ166.41, 165.77, 160.43, 131.96, 129.18, 127.08, 123.84, 62.26, 32.20, 14.19.
Embodiment 2
[0018] Example 2: Ethyl 5-p-methylphenyl-1,3,4-oxadiazole-2-acetate (compound 2)
[0019]
[0020] In a similar method to Example 1, using 4-methylbenzohydrazide as a raw material, the reaction was carried out to obtain compound 2 (106 mg, 86%). 1 H NMR (500MHz, CDCl 3 )δ7.93(d, J=7.8Hz, 2H), 7.30(d, J=7.8Hz, 2H), 4.24(q, J=7.1Hz, 2H), 4.02(s, 2H), 2.42(s, 3H), 1.28 (t, J=7.1Hz, 3H); 13 C NMR (125MHz, CDCl 3 )δ166.47, 165.92, 160.19, 142.50, 129.86, 127.01, 121.03, 62.22, 32.18, 21.75, 14.18.
Embodiment 3
[0021] Example 3: Ethyl 5-p-fluorophenyl-1,3,4-oxadiazole-2-acetate (compound 3)
[0022]
[0023] In a similar method to Example 1, using 4-fluorobenzoic hydrazide as the raw material, the reaction was carried out to obtain compound 3 (114 mg, 91%). 1 H NMR (500MHz, CDCl 3 )δ8.08-8.00(m, 2H), 7.22-7.14(m, 2H), 4.24(q, J=7.1Hz, 2H), 4.02(s, 2H), 1.28(t, J=7.1Hz, 3H) ); 13 C NMR (125MHz, CDCl 3 )δ166.35, 164.95(d, J=253.0Hz), 164.93, 160.44, 129.35(d, J=9.0Hz), 120.15(d, J=3.2Hz), 116.51(d, J=22.3Hz), 62.26 , 32.12, 14.16; 19 F NMR (376MHz, CDCl 3 )δ-106.70.
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Abstract
The invention provides 1, 3, 4-oxadiazoleethyl acetate and a synthesis method of the 1, 3, 4-oxadiazoleethyl acetate. According to the method, under the alkaline condition, acylhydrazine and ethyl 3, 3, 3-trifluoropropionate are subjected to [4 + 1] cycloaddition reaction, and 1, 3, 4-oxadiazoleethyl acetate can be obtained with good yield and wide substrate universality. Compared with the traditional method for synthesizing the 1, 3, 4-oxadiazole structure, the method provided by the invention has the following obvious advantages of short synthesis route, cheap and easily available raw materials, mild reaction conditions and simplicity in operation, and is particularly suitable for preparing related products in a large scale.
Description
technical field [0001] The invention relates to an ethyl 1,3,4-oxadiazole acetate and a synthesis method thereof, belonging to the field of organic synthesischemistry. Background technique [0002] 1,3,4-oxadiazole structure, as an important advantageous skeleton, widely exists in organic compounds with physiological activity, and exhibits anticancer, antibacterial, anti-inflammatory, antispasmodic, antiangiogenesis, analgesic, etc. kind of activity. Many commercially available drugs, such as nexadil, raltegravir, zipotetan, etc., contain a 1,3,4-oxadiazole backbone. 1,3,4-oxadiazoles can act as bioisosteres for carboxylic acid, ester and amide functional groups during drug development; in many agrochemicals, such as some herbicides, pesticides and plant growth regulators The structure also contains this dominant skeleton. In addition to a wide range of biological activities, the 1,3,4-oxadiazole structure also exhibits excellent electron transport properties, so it has ...
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IPC IPC(8): C07D271/10C07D413/04C07D417/04
CPCC07D271/10C07D413/04C07D417/04Y02A50/30
Inventor 李方怿赵兰所同川
Owner TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE