Amide compound and synthesis method thereof

Abstract

The synthesis method comprises the following steps: by taking a carboxylic acid compound and a secondary amine compound as reaction raw materials and triphenyl phosphite and p-xylene with the equivalent weight of 0.5 as solvents, heating to 160 DEG C in a nitrogen atmosphere, and effectively reacting for 24 hours, so as to obtain the phosphite-mediated amide compound generated by carboxylic acid and secondary amine. And the amide compound is obtained with high yield. The method has the advantages of high yield, simplicity and convenience in operation, few additives, low cost, no pollution and the like, and has certain feasibility for realizing industrial production.

Description

[Technical field]

[0001] The invention belongs to the field of organic synthesis, and in particular relates to an amide compound generated by carboxylic acid and amine mediated by phosphite and a synthesis method thereof. [Background technology]

[0002] Amide bonds are widely present in bioactive molecules, organic functional materials and fine chemicals, and have very rich molecular structures and unique biological activities. For example, compounds with the structure of β-lactam compounds have a wide range of antibacterial activity, can inhibit bacterial cell wall synthesis, and activate bacterial autolytic enzymes (GSSingh, P.Luntha, Eur.J.Med.Chem., 2009, 44, 2265.). In addition, amide bonds can also be used to combine carboxylic acids and amino drugs for prodrug design to improve drug efficacy and reduce side effects. For example, aryl alkanoic acid non-steroidal anti-inflammatory drug ibuprofen is condensed with piperazine antihistamine diphenylmethyl piperazine to obtain an amide prodrug, which can reduce the direct stimulation of ibuprofen carboxyl to the gastrointestinal tract, and at the same time, it can cooperate with diphenylmethyl piperazine to enhance the anti-allergic effect (RJWoJnar, T.Hearn, S.Starkweather., Journal of Allergy and Clinical Immunology, 1980, 66, 37-45.). In addition, amide bonds are also chemical bonds connecting carboxylic acids and amines, and play a very important role in the fields of peptide synthesis and protein (R. Maini, H. Kimura, R. Takatsu Ji, et al., J. Am. Chem. Soc., 2019, 141, 20004-20008.). Therefore, how to quickly and efficiently construct amide bonds has always been an important part of the field of organic synthesis.

[0003] The traditional direct amidation reaction requires the addition of an equivalent amount of coupling reagent to activate the carboxylic acid, and for some less active carboxylic acids and amines, an additional equivalent amount of activating reagent, such as 1-hydroxybenzotriazole (HOBT), is required to improve the reactivity of the active intermediate (DSTreitler, A.S. Marriott, J. Chadwick, et al., Org. Process Res. Dev., 2019, 23, 2562-2566.). These methods have low atomic utilization, and HOBT may explode when heated under closed conditions. Therefore, in the past few decades, chemists have developed many methods for synthesizing amide compounds, such as metal catalysis ( D. Kumar , SR Vemula , GR Cook ,ACS Catal.,2016,6,4920-4945.), anhydride activation ( N.Takahashi, H. Iwasawa , T. Kinashi , Chem. Commun., 2023, 59, 7391-7394.), acyl chloride amination ( M. Balkenhohl , C. DS Roman ,et al.,Org.Lett.,2017,19,536-539.) etc. These methods also have some shortcomings, such as metal catalysis requires the use of equivalent oxidants, and acid anhydrides and acyl chlorides require the activation of carboxylic acids into active derivatives. Therefore, the development of new mild and efficient synthetic methods to construct structurally diverse amides is still of great research value.

[0004] Phosphite is a trivalent organic phosphate compound, which is mainly used as an antioxidant stabilizer for high molecular polymers such as polyethylene, polypropylene, polyvinyl chloride, ABS resin, epoxy resin, synthetic rubber and polyester. In addition, due to its unique chemical activity, it is widely used as a ligand or reagent in the synthesis of various natural products and drug molecules. Therefore, we have invented a method for synthesizing amide compounds by direct condensation of carboxylic acid and amine mediated by phosphite. This method does not require special equipment, does not require the addition of metal catalysts, oxidants and strong bases, etc., is simple to operate, has few additives, high yield, a wide range of applications, and has certain industrial application value. At present, there are no public documents and patents at home and abroad on the synthesis of amide compounds by the reaction of carboxylic acid and amine mediated by phosphite. [Summary of the invention]

[0005] The object of the present invention is to provide a method for efficiently synthesizing amide compounds by using phosphite as an additive and carboxylic acid compounds and amine compounds as raw materials. The method does not require the addition of metal catalysts, oxidants and strong bases, has the advantages of simple operation and high yield, and has certain feasibility for realizing its industrial production.

[0006] In order to achieve the above-mentioned object of the invention, the present invention proposes the following technical solutions:

[0007] A phosphite-mediated reaction of carboxylic acid and amine to generate an amide compound and a synthesis method thereof, wherein the general structural formula of the amide compound I is as follows:

[0008]

[0009] R includes, but is not limited to, phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-aminophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-iodophenyl, and 1-adamantyl. 1 , R 2Including but not limited to hydrogen, methyl, benzyl, ethyl, 4-phenylbenzyl, phenyl, 3-methylphenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-cyanophenyl, 4-nitrophenyl, 2,4-dichlorophenyl, 2-methylphenyl, 2-biphenyl, 4-trifluoromethylphenyl, 2-naphthyl, 2-pyridyl, 2-propyl, tert-butyl, 2-furylmethyl, n-octyl and the like.

[0010] The structural formulas of the raw material carboxylic acid ⅠⅠ and the raw material amine Ш are as follows:

[0011]

[0012] The synthesis method of compound I is characterized in that, under a nitrogen atmosphere, the additive is 0.5 equivalent of triphenyl phosphite, p-xylene is used as the solvent, the reaction time is 24 hours at 160°C.

[0013] Wherein R is, but is not limited to, phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-aminophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-iodophenyl, and 1-adamantyl. 1 , R 2 Including but not limited to hydrogen, methyl, benzyl, ethyl, 4-phenylbenzyl, phenyl, 3-methylphenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-cyanophenyl, 4-nitrophenyl, 2,4-dichlorophenyl, 2-methylphenyl, 2-biphenyl, 4-trifluoromethylphenyl, 2-naphthyl, 2-pyridyl, 2-propyl, tert-butyl, 2-furylmethyl, n-octyl and the like.

[0014] Preferably, the phosphorus activator may be: triaryl phosphite, trialkyl phosphite, diaryl phosphite, dialkyl phosphite.

[0015] Preferably, the organic solvent may be p-xylene, toluene, 1,4-dioxane, or tetrahydrofuran.

[0016] The synthesis method of a class of amide compounds provided by the present invention is a class of green and efficient synthesis route, which has the advantages of: no need to add metal catalysts, oxidants and strong bases, high yield of target products, simple reaction operation, few additives, and green and pollution-free.

Brief Description of the Drawings

[0017] Attached photos Figure 1 Shown is a route map for preparing amide compounds provided by the present invention. [Specific implementation method]

[0018] The present invention provides a method for synthesizing amide compounds, see the attached drawings Figure 1: Carboxylic acid compounds and amines are used as raw materials, p-xylene is used as solvent, 0.5 equivalents of triphenyl phosphite are placed in a reaction container, heated to 160°C under a nitrogen atmosphere, and reacted for 24 hours. After the reaction is completed, the corresponding target product is separated and purified by column chromatography to obtain the corresponding target product.

[0019] The present invention is further described below in conjunction with some specific preparation examples:

[0020] Preparation Example 1

[0021] 0.2 mmol of benzoic acid, 1.5 equivalents of diethylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 70%. 1 H NMR (400 MHz, CDCl 3 ): δ7.36(s,5H),3.53(s,2H),3.23(s,2H),1.23(s,3H),1.09(s,3H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ171.3,137.2,129.0,128.3,126.2,43.2,39.2,14.1,12.9.

[0022] Preparation Example 2

[0023] 0.2 mmol of p-toluic acid, 1.5 equivalents of diethylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 75%. 1 H NMR (400 MHz, CDCl 3 ): δ7.08(d,J=6.8Hz,2H),7.00(d,J=7.6Hz,2H),3.34(s,2H),3.08(s,2H),2.18(s,3H),1.07-0.93(m,6H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ171.4,139.0,134.2,128.9,126.3,43.2,39.2,21.3,14.1,12.9.

[0024] Preparation Example 3

[0025] 0.2 mmol of p-methoxybenzoic acid, 1.5 equivalents of diethylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 68%. 1 H NMR (400 MHz, CDCl 3 ): δ7.33(d,J=8.4Hz,2H),6.88(d,J=8.8Hz,2H),3.81(s,3H),3.40(s,4H),1.20(d,J=29.6Hz,6H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ171.2,160.2,129.4,128.1,113.6,55.2,43.3,39.3,14.1,13.0.

[0026] Preparation Example 4

[0027] 0.2 mmol of p-phenoxybenzoic acid, 1.5 equivalents of diethylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 60%. 1 H NMR (400 MHz, CDCl 3 ): δ7.38-7.32(m,4H),7.13(t,J=7.6Hz,1H),7.03-6.97(m,4H),3.41(d,J=72.0Hz,4H),1.18(s,6H). 13 C{ 1 H}NMR (100MHz, CDCl 3 ): δ170.8,158.2,156.3,131.7,129.8,128.2,123.7,119.3,118.0,43.3,39.3,14.0,12.9.

[0028] Preparation Example 5

[0029] Add the Amino 0.2 mmol of benzoic acid, 1.5 equivalents of diethylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 49%. 1 H NMR (400 MHz, CDCl 3): δ7.23 -7.22(m,1H),7.21-7.20(m,1H),6.66-6.65(m,1H),6.63-6.62(m,1H),3.84(s,2H),3.41(s,4H),1.16(t,J=6.8Hz,6H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ171.6,147.5,128.3,127.0,114.3,40.5,13.4.

[0030] Preparation Example 6

[0031] 0.2 mmol of p-fluorobenzoic acid, 1.5 equivalents of diethylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 66%. 1 H NMR (400 MHz, CDCl 3 ): δ7.38-7.33(m,2H),7.09-7.03(m,2H),3.51(s,2H),3.24(s,2H),1.23-1.11(m,6H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ170.3, 162.97 (d, J = 248.8Hz), 133.17 (d, J = 3.5Hz), 128.42 (d, J = 8.5Hz), 115.39 (d, J = 21.7Hz), 43.3, 39.4, 14.0, 12.8.

[0032] Preparation Example 7

[0033] 0.2 mmol of p-chlorobenzoic acid, 1.5 equivalents of diethylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 58%. 1 H NMR (400 MHz, CDCl 3 ): δ7.36-7.34(m,2H),7.31-7.28(m,2H),3.51(s,2H),3.22(s,2H),1.23-1.09(m,6H). 13 C{1H}NMR (100MHz, CDCl 3): δ170.1,135.5,135.0,128.6,127.7,43.2,39.3,14.1,12.8.

[0034] Preparation Example 8

[0035] 0.2 mmol of p-chlorobenzoic acid, 1.5 equivalents of diethylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 49%. 1 H NMR (400 MHz, CDCl 3 ): δ7.48-7.45(m,2H),7.20-7.17(m,2H),3.47(s,2H),3.17(s,2H),1.11(d,J=49.2Hz,6H). 13 C{ 1 H}NMR (100MHz, CDCl 3 ): δ170.1,136.0,131.6,128.0,123.3,43.2,39.3,14.2,12.8.

[0036] Preparation Example 9

[0037] 0.2 mmol of p-iodobenzoic acid, 1.5 equivalents of diethylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 61%. 1 H NMR (400 MHz, CDCl 3 ): δ7.72(t,J=2.0Hz,1H),7.71(t,J=1.6Hz,1H),7.10(t,J=2.0Hz,1H),7.08(t,J=2.0Hz,1H),3.50(s,2H),3.21(s,2H),1.23-1.08(m,6H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ170.2,137.4,136.5,128.0,95.0,43.2,39.3,14.1,12.8.

[0038] Preparation Example 8

[0039] Add 0.2 mmol of benzoic acid, 1.5 equivalents of N-methylbenzylamine, 0.5 equivalent of triphenyl phosphite, and 1 mL of p-xylene to a 10 mL tubular reactor. Under a nitrogen atmosphere, heat to 160 °C and react for 24 h. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 69%. 1 H NMR(400MHz,CDCl 3 ):δ7.47-7.45(m,2H),7.36(s,6H),7.31-7.27(m,1H),7.18(s,1H),4.64(d,J=100.8Hz,2H),2.95(d,J=68.4Hz,3H). 13 C{1H}NMR(100MHz,CDCl 3 ):δ172.3,171.5,137.0-136.1(m),129.6,128.8-128.1(m),124.5(d,J=7.0Hz),126.8(d,J=21.2Hz),55.1,50.7,36.9,33.1.

[0040] Preparation Example 9

[0041] Add 0.2 mmol of benzoic acid, 1.5 equivalents of N-ethylaniline, 0.5 equivalent of triphenyl phosphite, and 1 mL of p-xylene to a 10 mL tubular reactor. Under a nitrogen atmosphere, heat to 160 °C and react for 24 h. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 73%. 1 H NMR(400MHz,CDCl 3 ):δ7.22-6.95(m,10H),3.92-3.90(m,2H),1.16-1.13(m,3H). 13 C{1H}NMR(100MHz,CDCl 3 ):δ170.1,143.1,136.2,129.4,129.0,128.6,127.9,127.6,126.5,45.3,12.9.

[0042] Preparation Example 10

[0043] Add 0.2 mmol of benzoic acid, 1.5 equivalents of aniline, 0.5 equivalent of triphenyl phosphite, and 1 mL of p-xylene to a 10 mL tubular reactor. Under a nitrogen atmosphere, heat to 160 °C and react for 24 h. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 84%. 1 H NMR(400MHz,CDCl 3): δ7.89-7.84(m,3H),7.65(dd,J=8.8,1.2Hz,2H),7.56-7.53(m,1H),7.51-7.47(m,2H),7.40-7.36(m,2H),7.18-7.14(m,1H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.8,137.9,135.0,131.8,129.1,128.8,127.0,124.6,120.2.

[0044] Preparation Example 11

[0045] 0.2 mmol of benzoic acid, 1.5 equivalents of m-methylaniline, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 70%. 1 H NMR (400 MHz, CDCl 3 ): δ7.90-7.88(m,3H),7.60-7.54(m,2H),7.53-7.48(m,2H),7.45(d,J=8.0Hz,1H),7.30-7.28(m,1H),7.00(d,J=7.6Hz,1H),2.39(s,3H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.7,139.0,137.8,135.0,131.8,128.9,128.7,127.0,125.3,120.8,117.2,21.5.

[0046] Preparation Example 12

[0047] 0.2 mmol of benzoic acid, 1.5 equivalents of p-methylaniline, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 69%. 1 H NMR (400 MHz, CDCl 3 ): δ7.88-7.85(m,2H),7.77(s,1H),7.56-7.46(m,5H),7.18(d,J=8.0Hz,2H),2.34(s,3H). 13 C{1H}NMR (100MHz, CDCl 3): δ165.7,135.3,135.0,134.2,131.6,129.5,128.6,127.0,120.3,21.0.

[0048] Preparation Example 13

[0049] 0.2 mmol of benzoic acid, 1.5 equivalents of p-tert-butylaniline, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 70%. 1 H NMR (400 MHz, CDCl 3 ): δ8.01(s,1H),7.86(s,1H),7.84(d,J=1.6Hz,1H),7.57(d,J=8.1Hz,2H) ,7.54-7.50(m,1H),7.46-7.42(m,2H),7.38(t,J=2.0Hz,1H),1.33(s,9H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.8,147.5,135.3,135.0,131.6,128.7,128.6,127.0,126.9,125.8,120.1,120.0,34.4,31.3.

[0050] Preparation Example 14

[0051] 0.2 mmol of benzoic acid, 1.5 equivalents of p-cyanoaniline, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 40%. 1 H NMR (400 MHz, CDCl 3 ): δ8.16(s,1H),7.88-7.86(m,2H),7.80(d,J=8.4Hz,2H),7.64(d,J=8.8Hz,2H),7.60-7.57(m,1H),7.52-7.48(m,2H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.9,142.0,134.1,133.4,132.5,129.0,127.1,119.9,118.8,107.4.

[0052] Preparation Example 15

[0053] 0.2 mmol of benzoic acid, 1.5 equivalents of p-nitroaniline, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 45%. 1 H NMR (400 MHz, CDCl 3 ): δ8.29-8.28(m,1H),8.27-8.25(m,1H),8.11(s,1H),7.90-7.88(m,2H),7.87-7.83(m,2H),7.63-7.60(m,1H),7.55-7.52(m,2H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ168.9,148.0,143.3,127.3,123.8,43.2,39.5,14.2,12.8.

[0054] Preparation Example 16

[0055] 0.2 mmol of benzoic acid, 1.5 equivalents of benzocaine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 50%. 1 H NMR (400 MHz, CDCl 3 ): δ8.24-7.48(m,4H),6.63-6.62(m,2H),4.31-4.08(m,4H),1.74-1.25(m,5H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ166.7,150.7,132.1,131.5,130.8,128.8,127.1,120.0,119.1,113.7,60.3,14.4.

[0056] Preparation Example 17

[0057] 0.2 mmol of benzoic acid, 1.5 equivalents of 2,4-dichloroaniline, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 40%. 1 H NMR (400 MHz, CDCl 3): δ8.56-8.53(d,J=8.8Hz,1H),8.39(s,1H),7.92-7.90(m,2H),7.62-7.58( m,1H),7.55-7.51(m,2H),7.43(d,J=2.4Hz,1H),7.32(dd,J=8.8,2.0Hz,1H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.2,134.2,133.5,132.4,129.2,129.0,128.7,128.0,127.1,123.5,122.1.

[0058] Preparation Example 18

[0059] 0.2 mmol of benzoic acid, 1.5 equivalents of o-methylaniline, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 68%. 1 H NMR (400 MHz, CDCl 3 ): δ7.91(d,J=8.0Hz,1H),7.88-7.86(m,2H),7.70(s,1H),7.57-7.52(m,1H),7 .50-7.46(m,2H),7.24-7.21(t,J=7.2Hz,2H),7.12-7.08(m,1H),2.32(s,3H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.6,135.7,135.0,131.8,130.5,129.2,128.8,127.0,126.9,125.3,123.1,17.8.

[0060] Preparation Example 19

[0061] 0.2 mmol of benzoic acid, 1.5 equivalents of o-phenylaniline, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 48%. 1 H NMR (400 MHz, CDCl 3): δ8.43(d,J=8.4Hz,1H),7.90(s,1H),7.50-7.48(m,2H),7.43-7.28(m,9H),7.20(dd,J=7.6,1.6Hz,1H),7.12(t,J=7.2Hz,1H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.0,138.0,134.9,134.7,132.3,131.7,130.0,129.3,129.2,128.7,128.6,128.2,126.8,124.3,121.1.

[0062] Preparation Example 20

[0063] 0.2 mmol of benzoic acid, 1.5 equivalents of p-trifluoromethylaniline, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 80%. 1 H NMR (400 MHz, CDCl 3 ): δ7.94(s,1H),7.90-7.89(m,1H),7.87(t,J=2.0Hz,1H),7.79(d,J=8.8Hz,2H),7.64(d,J=8.4Hz,2H),7.61-7.57(m,1H),7.54-7.50(m,2H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.8,140.9,134.4(d,J=4.1Hz),132.3,129.6,128.9,127.0,126.4(d,J=3.9Hz),120.1,119.7,111.1,29.7.

[0064] Preparation Example 21

[0065] 0.2 mmol of 1-adamantanic acid, 1.5 equivalents of aniline, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 83%. 1 H NMR (400 MHz, CDCl 3): δ7.55-7.52(m,2H),7.33-7.29(m,3H),7.09(t,J=7.2Hz,1H),2.10(s,3H),1.97(d,J=2.4Hz,6H),1.80-1.72(m,6H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.8,140.9,134.4(d,J=4.1Hz),132.3,129.6,128.9,127.0,126.4(d,J=3.9Hz),120.1,119.7,111.1,29.7.

[0066] Preparation Example 22

[0067] 0.2 mmol of benzoic acid, 1.5 equivalents of 2-naphthylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 46%. 1 H NMR (400 MHz, CDCl 3 ): δ8.33(s,1H),8.16(s,1H),7.92-7.90(m,2H),7.82-7.78(m,3H),7.61(dd,J=4.8,2.0Hz,1H),7.57-7.53(m,1H),7.49-7.40(m,4H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.9,135.3,134.9,133.8,131.9,130.7,128.9,128.8,127.7,127.6,127.0,126.5,125.1,120.1,117.0.

[0068] Preparation Example 23

[0069] 0.2 mmol of benzoic acid, 1.5 equivalents of pyridine 2-amine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 30%. 1 H NMR (400 MHz, CDCl 3): δ8.87(s,1H),8.40(d,J=8.4Hz,1H),8.25(dd,J=4.8,0.8k Hz,1H),7.95-7.92(m,2H),7.78-7.74(m,1H),7.59-7.55(m,1H),7.51-7.47(m,2H),7.08-7.05(m,1H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ165.8,151.6,147.8(d,J=2.7Hz),138.5,134.2,132.2,128.8,127.2,119.9,114.2(d,J=3.9Hz).

[0070] Preparation Example 24

[0071] 0.2 mmol of benzoic acid, 1.5 equivalents of monoisopropylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 56%. 1 H NMR (400 MHz, CDCl 3 ): δ7.75-7.73(m,2H),7.48-7.44(m,1H),7.41-7.37(m,2H),6.11(s,1H),4.39-4.17(m,1H),1.25(s,3H),1.24(s,3H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ166.7,134.9,131.2,128.4,126.8,41.8,22.8.

[0072] Preparation Example 25

[0073] 0.2 mmol of benzoic acid, 1.5 equivalents of tert-butylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 60%. 1 H NMR (400 MHz, CDCl 3 ): δ7.72-7.70(m,2H),7.48-7.44(m,1H),7.41-7.37(m,2H),6.08-5.86(m,1H),1.46(s,9H). 13 C{1H}NMR (100MHz, CDCl 3): δ166.9,135.8,131.0,128.4,126.6,51.5,28.8.

[0074] Preparation Example 26

[0075] 0.2 mmol of benzoic acid, 1.5 equivalents of p-phenylbenzylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 74%. 1 H NMR (400 MHz, CDCl 3 ): δ7.82-7.80(m,2H),7.60-7.57(m,4H),7.53-7.50(m,1H),7.46-7.43(m,6H),7.37-7.33(m,1H),6.43(s,1H),4.70(d,J=5.6Hz,2H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ167.3,140.7,137.2,134.3,131.6,128.8,128.6,128.4,127.5,127.4,127.1,126.9,43.9.

[0076] Preparation Example 27

[0077] 0.2 mmol of benzoic acid, 1.5 equivalents of p-furan 2-methylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 60%. 1 H NMR (400 MHz, CDCl 3 ): δ7.79-7.77(m,2H),7.49-7.37(m,3H),6.53(s,1H),6.32(d,J=2.4Hz,2H),4.64(d,J=3.2Hz,2H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ167.2,151.1,142.3,134.1,131.6,128.5,127.0,110.5,107.7,37.0.

[0078] Preparation Example 28

[0079] 0.2 mmol of benzoic acid, 1.5 equivalents of p-n-octylamine, 0.5 equivalents of triphenyl phosphite, and 1 mL of p-xylene were added to a 10 mL tubular reactor, and heated to 160° C. for 24 hours under a nitrogen atmosphere. After the reaction, the product was separated and purified by column chromatography, and the separation yield was 55%. 1 H NMR (400 MHz, CDCl 3 ): δ7.76-7.74(m,2H),7.51-7.47(m,1H),7.44-7.41(m,2H),6.11(s,1H),3.46( dd,J=13.2,7.2Hz,2H),1.65-1.58(m,4H),1.38-1.27(m,8H),0.89-0.86(m,2H). 13 C{1H}NMR (100MHz, CDCl 3 ): δ167.5,134.9,131.3,128.5,126.8,40.1,31.8,29.7,29.3,29.2,27.0,22.6,14.1.

[0080] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention should be based on the attached claims.

Claims

1. An amide compound and a method for synthesizing the same, wherein the general structural formula of the amide compound I is as follows: Wherein R includes but is not limited to phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-aminophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-iodophenyl, 1-adamantyl. R1 and R2 include but are not limited to hydrogen, methyl, benzyl, ethyl, 4-phenylbenzyl, phenyl, 3-methylphenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-cyanophenyl, 4-nitrophenyl, 2,4-dichlorophenyl, 2-methylphenyl, 2-biphenyl, 4-trifluoromethylphenyl, 2-naphthyl, 2-pyridyl, 2-propyl, tert-butyl, 2-furylmethyl, n-octyl, etc. The synthesis method of compound I is characterized by: Using carboxylic acid compounds and secondary amine compounds as raw materials, 0.5 equivalent of triphenyl phosphite and p-xylene as solvent, the reaction was carried out at 160°C in a nitrogen environment for 24 hours to obtain amide compound I in high yield.

2. The synthesis method according to claim 1, characterized in that The structural formulas of the raw material carboxylic acid compound II and the raw material amine compound Ш are as follows: Wherein said R includes but is not limited to phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-aminophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-iodophenyl, 1-adamantyl. R1 and R2 include but are not limited to hydrogen, methyl, benzyl, ethyl, 4-phenylbenzyl, phenyl, 3-methylphenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-cyanophenyl, 4-nitrophenyl, 2,4-dichlorophenyl, 2-methylphenyl, 2-biphenyl, 4-trifluoromethylphenyl, 2-naphthyl, 2-pyridyl, 2-propyl, tert-butyl, 2-furylmethyl, n-octyl, etc.

3. The synthesis method according to claim 1, characterized in that Under nitrogen atmosphere, the catalyst is 0.5 equivalent of triphenyl phosphite, p-xylene is the solvent, the temperature is 160°C, and the reaction time is 24 hours.

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