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Preparation method of amide derivative

A technology of amide derivatives and substances, which is applied in the field of asymmetric urea and thiocarbamate compounds, can solve the problems of harsh reaction conditions, low conversion rate, unfavorable large-scale application, etc., and achieve simple operation process and good yield , The effect of wide substrate applicability

Active Publication Date: 2020-05-08
ZHEJIANG UNIV OF TECH
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  • Abstract
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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.

Method used

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  • Preparation method of amide derivative
  • Preparation method of amide derivative
  • Preparation method of amide derivative

Examples

Experimental program
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Effect test

Embodiment 1

[0024] Embodiment 1: Preparation of 1-(4-methoxyphenyl)-3-phenylurea

[0025] 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 2 hours, 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%.

[0026] 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).

[0027] 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.

[0028]

Embodiment 2

[0029] Embodiment 2: Preparation of 1-benzyl-3-phenylurea

[0030] 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%.

[0031] 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).

[0032] 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.

[0033]

Embodiment 3

[0034] Embodiment 3: Preparation of 3-phenyl-N-methyl-N-phenylurea

[0035] In a 500mL single-necked flask, add 19.20g (140mmol) of benzohydroxamic acid (I), N-methylaniline (II-3, X=N, R2 =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%.

[0036] 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).

[0037] 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.

[0038]

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Abstract

The invention provides a preparation method of an amide derivative. The method comprises the following steps: taking hydroxamic acid and an amine or thiol compound as raw materials, sequentially adding alkali and a solvent, carrying out a reaction for 2-7 hours at the temperature of 25-50 DEG C in an SO2F2 atmosphere, and after the reaction is finished, carrying out aftertreatment on a reaction solution to obtain the asymmetric urea compound or thiocarbamate compound. According to the invention, cheap, easily available and environment-friendly SO2F2 is used as an accelerant to efficiently promote the generation of isocyanate intermediates and form C-N and C-S bonds. The generation of isocyanate avoids the use of a large amount of halogen or azide dangerous reagents, so that the compound can be used as a green substitute for standard treatment conditions in Curtius rearrangement and Hofmann rearrangement reactions. The substrate is wide in applicability, and the corresponding asymmetricurea and thiocarbamate compounds can be obtained at a relatively good yield. The operation process is simple and suitable for large-scale preparation.

Description

[0001] (1) Technical field [0002] 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. [0003] (2) Background technology [0004] 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 ...

Claims

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Application Information

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Patent Type & Authority Applications(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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