A kind of preparation method of 4-substituted phenylthioisoquinolin-1(2h)-one compound

A technology of phenylthioisoquinoline and ketone compounds, which is applied in the field of organic synthetic chemistry, can solve problems such as harsh reaction conditions, long reaction routes, and poor atom economy, and achieve easy-to-obtain raw materials, mild conditions, and high atom economy Effect

Inactive Publication Date: 2021-05-07
NANKAI UNIV
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Problems solved by technology

However, there are obvious disadvantages in this method: (1) harsh reaction conditions, such as the need to react with butyllithium and methyllithium under low temperature, anhydrous and oxygen-free conditions; (2) the reaction route is long and needs to undergo bromination , two-step lithium salination and reaction with disulfide in four steps to obtain the target product
Poor atom economy, produces a lot of waste

Method used

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  • A kind of preparation method of 4-substituted phenylthioisoquinolin-1(2h)-one compound
  • A kind of preparation method of 4-substituted phenylthioisoquinolin-1(2h)-one compound
  • A kind of preparation method of 4-substituted phenylthioisoquinolin-1(2h)-one compound

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017]

[0018] At room temperature, add isoquinolin-1(2H)-one (10mmol), bis(4-methylphenyl) disulfide (15mmol), silver hexafluoroantimonate (7mmol) and Dichloroethane (6 mL). The reaction mixture was then reacted at 80°C for 12 hours. Stop reaction, concentrate under reduced pressure to obtain crude product, wash with the mixed eluent of sherwood oil and ethyl acetate at last, flash column chromatography obtains corresponding product 4-(4-methylphenylsulfanyl) isoquinoline-1 ( 2H)-ketone. Yield 96%; white solid, melting point 165-167°C; 1 H NMR (400MHz, CDCl 3 )δ11.74(s, 1H), 8.41(d, J=8.0Hz, 1H), 7.96(d, J=8.1Hz, 1H), 7.71(s, 1H), 7.62(t, J=7.5Hz, 1H), 7.41(t, J=7.6Hz, 1H), 7.03(dd, J=20.6, 8.1Hz, 4H), 2.26(s, 3H); 13 C NMR (101MHz, CDCl 3 )δ164.11, 138.31, 135.79, 135.25, 133.38, 130.81, 129.83, 127.83, 127.40, 127.11, 126.11, 125.51, 109.06, 20.91.

Embodiment 2

[0020]

[0021] At room temperature, sequentially add isoquinolin-1(2H)-one (10mmol), bis(4-chlorophenyl) disulfide (11mmol), silver hexafluoroantimonate (8mmol) and di Ethyl chloride (6 mL). The reaction mixture was then reacted at 80°C for 11 hours. Stop reaction, concentrate under reduced pressure to obtain crude product, wash with the mixed eluent of sherwood oil and ethyl acetate at last, flash column chromatography obtains corresponding product 4-(4-chlorophenylsulfanyl) isoquinoline-1 (2H )-ketone. Yield 90%; white solid, melting point 158-160°C; 1 H NMR (400MHz, CDCl 3 )δ11.36(s, 1H), 8.46(d, J=7.9Hz, 1H), 7.91(d, J=8.0Hz, 1H), 7.68(d, J=9.0Hz, 2H), 7.56(t, J=7.5Hz, 1H), 7.17(d, J=8.1Hz, 2H), 7.06(d, J=8.1Hz, 2H); 13 C NMR (101MHz, CDCl 3 )δ164.01, 137.89, 135.90, 135.84, 133.56, 131.64, 129.17, 127.97, 127.70, 126.44, 125.38, 107.47, 100.00.

Embodiment 3

[0023]

[0024] At room temperature, sequentially add isoquinolin-1(2H)-one (10mmol), bis(2-fluorophenyl) disulfide (10mmol), silver hexafluoroantimonate (11mmol) and di Ethyl chloride (6 mL). The reaction mixture was then reacted at 100°C for 9 hours. Stop reaction, concentrate under reduced pressure to obtain crude product, wash with the mixed eluent of sherwood oil and ethyl acetate at last, flash column chromatography obtains corresponding product 4-(2-fluorophenylsulfanyl) isoquinoline-1 (2H )-ketone. Yield 90%; light yellow solid, melting point 175-177°C; 1 H NMR (400MHz, CDCl 3 )δ11.81(s, 1H), 8.46(d, J=9.0Hz, 1H), 8.00(d, J=8.0Hz, 1H), 7.75(s, 1H), 7.71(ddd, J=8.3, 7.3 , 1.4Hz, 1H), 7.59-7.53(m, 1H), 7.19-7.03(m, 2H), 6.95-6.84(m, 2H); 13 C NMR (101MHz, CDCl 3 )δ164.39, 159.49 (d, J C-F =244.8Hz), 138.15, 136.36, 133.57, 128.71 (d, J C-F =1.5Hz), 127.88, 127.66, 127.44 (d, J C-F =7.5Hz), 126.32, 125.34, 124.63 (d, J C-F =3.3Hz), 115.71, 115.50, 106.31.

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Abstract

The present invention relates to a kind of preparation method of 4-substituted phenylthioisoquinolin-1(2H)-ketone compound, comprising the following steps: raw material isoquinolin-1(2H)-ketone and diaryl disulfide Dissolve in dichloroethane, then add silver hexafluoroantimonate, react at 60-140°C for 6-12 hours, separate and purify the crude product after the reaction is terminated, and obtain 4-substituted phenylthioisoquinoline-1 (2H )-ketone compounds. The method has the advantages of simple and easy-to-obtain raw materials, simple operation without harsh reaction conditions such as anhydrous and oxygen-free, high yield, high selectivity, wide substrate adaptability, and easy purification of prepared products.

Description

[0001] (1) Technical field [0002] The invention belongs to the field of organic synthetic chemistry, and relates to a preparation method of 4-substituted phenylthioisoquinolin-1(2H)-one compounds, in particular to a direct utilization of isoquinone mediated by silver hexafluoroantimonate A method for synthesizing 4-substituted phenylthioisoquinolin-1(2H)-one compounds by oxidative coupling of lin-1(2H)-one and diaryl disulfide. [0003] (2) Background technology [0004] Isoquinolin-1(2H)-one compounds are an important class of organic structural units, which widely exist in various natural products, drug molecules and pharmaceutical intermediates with anticancer activities. 4-Thioisoquinoline- 1(2H)-one compound is one of the important branches, and its synthetic method mainly includes: first reacting isoquinolin-1(2H)-one with bromine to generate 4-bromoisoquinolin-1(2H)-one , and then react with methyllithium and butyllithium respectively at low temperature, and then reac...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D217/24
CPCC07D217/24
Inventor 朱有全何敬立牛芸霞韩廷峰李浩宇
Owner NANKAI UNIV
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