A kind of preparation method of amide derivative

A technology of amide derivatives and substances, applied in the field of asymmetric urea and thiocarbamate compounds, can solve the problems of unfavorable large-scale application, harsh reaction conditions, unfriendly environment, etc., and achieve a process suitable for large-scale preparation and operation Simple, good yield effect

Active Publication Date: 2022-01-25
ZHEJIANG UNIV OF TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the above methods have some disadvantages, such as the need for transition metals, harsh reaction conditions, low conversion rates, and highly toxic substances such as halogens or azide reagents. The system is not friendly to the environment and is not conducive to large-scale application.

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  • A kind of preparation method of amide derivative
  • A kind of preparation method of amide derivative
  • A kind of preparation method of amide derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Embodiment 1: Preparation of 1-(4-methoxyphenyl)-3-phenylurea

[0021] In a 500mL single-necked flask, add 19.20g (140mmol) of benzohydroxamic acid (I), p-methoxyaniline (II-1, X=N, R 2 = 4-OCH 3 -Ph) 17.24g (140mmol), 150mL water, 45.24g (2.5eq, 350mmol) DIPEA, in SO 2 f 2 In the atmosphere, stir at 25°C for 2h, filter after the reaction, and wash the filter cake with 10mL of acetonitrile until white to obtain 1-(4-methoxyphenyl)-3-benzene represented by formula (Ⅲ-1). Base urea 30.87g, yield 91%.

[0022] Proton NMR spectrum: (500MHz, DMSO-d 6 )(δ,ppm):8.57(s,1H),8.46(s,1H),7.44(d,J=7.6Hz,2H),7.39–7.33(m,2H),7.27(t,J=7.9Hz ,2H),6.95(t,J=7.3Hz,1H),6.90–6.84(m,2H),3.36(s,3H).

[0023] Carbon NMR spectrum: (126MHz, DMSO-d 6 )(δ, ppm): 154.93, 153.19, 140.36, 133.17, 129.20, 122.06, 120.49, 118.54, 114.45, 55.64.

[0024]

Embodiment 2

[0025] Embodiment 2: Preparation of 1-benzyl-3-phenylurea

[0026] In a 500mL single-necked flask, add 19.20g (140mmol) of benzohydroxamic acid (I), benzylamine (II-2, X=N, R 2 =Ph-CH 2 -) 15.00g (140mmol), 150mL dichloromethane, 63.94g (3.0eq, 420mmol) DBU, in SO 2 f 2 In the atmosphere, stir at 25°C for 1 h. After the reaction, filter and rinse with 10 mL of acetonitrile until white to obtain (Ⅲ-2) 1-benzyl-3-phenylurea 26.g with a yield of 83%.

[0027] Proton NMR spectrum: (500MHz, DMSO-d 6 )(δ,ppm):8.58(s,1H),7.44–7.40(m,2H),7.33(dt,J=10.9,7.1Hz,4H),7.27–7.18(m,3H),6.90(t, J=7.3Hz, 1H), 6.64(t, J=5.7Hz, 1H), 4.31(d, J=5.9Hz, 2H).

[0028] Carbon NMR spectrum: (126MHz, DMSO-d 6 )(δ, ppm): 155.24, 140.46, 128.63, 128.29, 127.76, 127.10, 126.70, 121.07, 117.69, 42.73.

[0029]

Embodiment 3

[0030] Embodiment 3: Preparation of 3-phenyl-N-methyl-N-phenylurea

[0031] In a 500mL single-necked flask, add 19.20g (140mmol) of benzohydroxamic acid (I), N-methylaniline (II-3, X=N, R 2=N-methylanilino) 15.00g (140mmol), 150mL acetonitrile, 18.10g (3.0eq, 420mmol) Na 2 CO 3 , at SO 2 f 2 In the atmosphere, stir at 30°C for 6h, filter after the reaction, rinse with 10mL of acetonitrile until white, and you can get 3-phenyl-N-methyl-N-phenylurea 25.98 shown in formula (III-3). g, yield 82%.

[0032] Proton NMR spectrum: (500MHz, DMSO-d 6 )(δ,ppm):8.12(s,1H),7.46–7.38(m,4H),7.33(dd,J=8.4,1.1Hz,2H),7.27–7.20(m,3H),6.95(t, J=7.3Hz,1H),3.28(s,3H).

[0033] Carbon NMR spectrum: (126MHz, DMSO-d 6 )(δ, ppm): 154.74, 144.09, 140.05, 129.24, 128.26, 126.22, 125.77, 122.04, 119.90, 37.55.

[0034]

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Abstract

The invention provides a method for preparing amide derivatives, the method comprising: using phenylhydroxamic acid and amines or thiol compounds as raw materials, adding alkali and solvent in sequence, 2 f 2 In the atmosphere, react at 25-50°C for 2-7h, after the reaction, the reaction solution is post-treated to obtain the asymmetric urea compound or thiocarbamate compound; friendly SO 2 f 2 As an accelerator, it can efficiently promote the formation of isocyanate intermediates and form C‑N and C‑S bonds. The formation of isocyanate avoids the use of a large amount of halogen or azide dangerous reagents, so it can be used as a green alternative to the standard treatment conditions of Curtis rearrangement and Hoffmann rearrangement. The substrate has wide applicability, and the corresponding asymmetric urea and thiocarbamate compounds can be obtained in good yield. The operation process is simple and suitable for large-scale preparation.

Description

(1) Technical field [0001] The present invention relates to utilizing sulfuryl fluoride (SO 2 f 2 ) as an accelerator to promote the Rosen rearrangement of hydroxamic acid to react with amines or thiols to synthesize amide derivatives: asymmetric urea and thiocarbamate compounds. (2) Background technology [0002] Asymmetric urea and thiocarbamate compounds in amide derivatives, especially aromatic asymmetric urea and thiocarbamate compounds, are widely used in natural products due to their special physical properties and chemical stability , pharmaceuticals, agrochemicals and catalysts. One of the more traditional methods for the preparation of asymmetric ureas is the stepwise reaction of phosgene and its derivatives with amines or amines and thiols. However, disadvantages such as the use of highly toxic reagents and low atom utilization limit the large-scale application of such methods. In recent years, in the presence of transition metal catalysts, the method of carbo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C273/18C07C275/34C07C275/28C07C333/08
CPCC07C273/1809C07C333/08C07C275/34C07C275/28
Inventor 丁成荣崔银张国富赵以勇吕井辉
Owner ZHEJIANG UNIV OF TECH
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