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CN-122010654-A - Preparation method and application of aromatic amide compound

CN122010654ACN 122010654 ACN122010654 ACN 122010654ACN-122010654-A

Abstract

The invention relates to a preparation method and application of an aromatic amide compound, in particular to an aromatic amide compound obtained by amidation reaction of a triazine ester compound under the catalysis of metallic iron (0), which uses cheap and widely stored iron as a catalyst, has simple process conditions, good yield and wide functional group tolerance.

Inventors

  • WANG QINGDONG
  • YANG JINMING

Assignees

  • 盐城锦明药业有限公司

Dates

Publication Date
20260512
Application Date
20260123

Claims (9)

  1. 1. A process for preparing a compound of formula I, Comprising the step of reacting a compound represented by formula II with a compound represented by formula III in the presence of metallic iron, , Wherein Ar 1 is selected from aryl or heteroaryl optionally substituted with one or more substituents selected from halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 3-6 cycloalkyl; Ar 2 is selected from aryl or heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, ester, C 3-6 cycloalkyl or phenyl.
  2. 2. The process of claim 1 wherein the reaction further comprises a lewis acid, preferably trimethylchlorosilane.
  3. 3. The process according to claim 1 or 2, wherein the solvent used for the reaction is selected from the group consisting of N-methylpyrrolidone, N-dimethylformamide or N, N-dimethylacetamide.
  4. 4. A process according to any one of claims 1 to 3, wherein the amount of metallic iron is 2 to 5 times, for example 4 times, the molar amount of the compound of formula II.
  5. 5. The method of any one of claims 1-4, wherein the compound of formula II is selected from the group consisting of: 、 、 、 、 、 、 、 、 、 Or (b) 。
  6. 6. The method of any one of claims 1-5, wherein the compound of formula III is selected from the group consisting of: 、 、 、 、 、 、 、 、 、 、 、 Or (b) 。
  7. 7. The method according to any one of claims 1 to 6, wherein the molar ratio of the compound of formula II to the compound of formula III is 1:1 to 1:4, preferably 1:1.5 to 1:3, for example 1:2.5.
  8. 8. The method according to any of claims 1-7, wherein the reaction temperature is 80-140 ℃, preferably 100-130 ℃, such as 120 ℃.
  9. 9. Use of the method of any one of claims 1-8 in the preparation of a medicament, fragrance or pesticide.

Description

Preparation method and application of aromatic amide compound Technical Field The invention belongs to the field of chemical medicines, and relates to a preparation method and application of an aromatic amide compound. Background Amides are an important class of molecules that are not only widely found in natural products, bioactive compounds and functional materials, but are also key components of synthetic organic chemistry. Generally, amides can be synthesized by coupling carbonyl compounds (e.g., carboxylic acids, esters) with amines. The use of nitroarenes as an attractive nitrogen source for the coupling of esters to amides has received considerable attention over the last decades because nitroarenes are also readily available and more stable than aryl amines. For example, in 2017, hu and colleagues semi-finished products reported that nickel could catalyze the reductive amidation of esters with nitroarenes in the presence of Zn and TMSCl (Nat. Commun. 2017, 8, 14878-14888 and ACS catalyst 2020, 10, 2845-2854). In 2019, the Cheung/Ma and Luo/Zeng groups reported that the same type of amidation could be performed by using Mn/tmcl and CrCl3// Mg/tmcl, respectively (org. Chem. Front. 2019, 6, 756-761 and org. Lett. 2019, 21, 1912-1916.). In addition, reductive transamidation of amides with nitroarenes has also been developed for the preparation of amides, primarily by the use of reduced metals (e.g., zn, mn) and TMSCl, as disclosed in Hu, ma, li, et al (ACS Catal 2017, 7, 7092-7096, J. Am. chem. Soc. 2018, 140, 6789-6792 and chem. Sci. 2018, 9, 655-659, etc.). The invention provides an aromatic amide compound which is applied to the amidation reaction of a triazine ester compound under the catalysis of metallic iron (0). Disclosure of Invention In one aspect, the present invention provides a process for preparing a compound of formula I Comprising the step of reacting a compound represented by formula II with a compound represented by formula III in the presence of metallic iron, , Wherein Ar 1 is selected from aryl or heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 3-6 cycloalkyl; Ar 2 is selected from aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted with one or more substituents selected from halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy, ester (e.g., methyl formate CH 3COO-）、C3-6 cycloalkyl or phenyl). In some embodiments, ar 1 in the compound of formula II is selected from phenyl optionally substituted with one or more substituents selected from halogen, cyano, C 1-6 alkyl, or C 1-6 alkoxy. In some embodiments, ar 1 in the compound of formula II is selected from phenyl optionally substituted with one or more substituents selected from halo C 1-6 alkyl or halo C 1-6 alkoxy. In some embodiments, ar 1 in the compound of formula II is selected from phenyl optionally substituted with one or more substituents selected from cyano, halo (e.g., fluoro, chloro or bromo), methyl, t-butyl, methoxy, trifluoromethyl or trifluoromethoxy. In some embodiments, the compound of formula II in the method is selected from: 、、、、、、、、、 Or (b) 。 In some embodiments, ar 2 in the compound of formula III is selected from phenyl or naphthyl optionally substituted with one or more substituents selected from halogen, cyano, C 1-6 alkyl, or C 1-6 alkoxy. In some embodiments, ar 2 in the compound of formula III is selected from phenyl or naphthyl optionally substituted with one or more substituents selected from halo C 1-6 alkyl or halo C 1-6 alkoxy. In some embodiments, ar 2 in the compound of formula III is selected from phenyl or naphthyl optionally substituted with one or more substituents selected from cyano, halo (e.g., fluoro, chloro or bromo), methyl, t-butyl, methoxy, trifluoromethyl, methyl formate (CH 3 COO-), trifluoromethoxy, or phenyl. In some embodiments, ar 2 in the compound of formula III is selected from thienyl optionally substituted with one or more substituents selected from halogen, cyano, C 1-6 alkyl, or C 1-6 alkoxy. In some embodiments, ar 2 in the compound of formula III is selected from thienyl optionally substituted with one or more substituents selected from halo C 1-6 alkyl or halo C 1-6 alkoxy. In some embodiments, ar 2 in the compound of formula III is selected from thienyl optionally substituted with one or more substituents selected from cyano, halo (e.g., fluoro, chloro or bromo), methyl, t-butyl, methoxy, trifluoromethyl, methyl formate (CH 3 COO-), trifluoromethoxy, or phenyl. In some embodiments, the compound of formula III in the method is selected from: 、、、、、、、、、、、 Or (b) 。 The method ensures that the reaction is carried out smoothly, wherein the use amount of the metallic iron is 2-5 times of the molar amount of the compound of the formula II, and can be 2.5, 2.6, 2.7, 2.8,