CN118479977A - A method for preparing amides from tertiary amines - Google Patents

Abstract

The invention discloses a method for preparing amides from tertiary amines, wherein an anhydride compound, a photocatalyst and a tertiary amine compound are dissolved in a dry organic solvent under an inert gas atmosphere, and a target amide compound is obtained by irradiating with blue light at room temperature. The photocatalyst is 4CzIPN, [Ir(dF)(CF ₃ )ppy ₂ (dtbbpy)]PF ₆ , Mes‑Acr ⁺ ClO ₄ , fac‑Ir(ppy) ₃ or Eosin Y. The invention mixes an anhydride compound and a tertiary amine compound, adds a metal-free organic photocatalyst and places it under light, and the amide compound can be successfully prepared. The method can reduce the cost required for the experiment and greatly reduce the production cost. The invention has mild reaction conditions, high reaction selectivity, is green and environmentally friendly, and is low in price, and is worthy of promotion and application.

Description

A method for preparing amides from tertiary amines

Technical Field

The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for preparing amide from tertiary amine.

Background Art

Tertiary amines and their derivatives, such as alpitant (anxiolytic), bupivacaine (labor analgesia), enzalutamide (anti-prostate cancer), and polyflubenzuronide (insecticide), have important application value in drug synthesis, biomedicine, and pesticides due to their unique biological activity. Therefore, the green and efficient synthesis of tertiary amide bonds has become a research hotspot in recent years.

Tertiary amides are synthesized by the reaction of carboxylic acids or pre-activated carboxylic acids (esters, acid chlorides, anhydrides, etc.) with secondary amines, and an equivalent condensing agent or activating agent needs to be added; transition metal-catalyzed carbonylation coupling reactions can synthesize tertiary amides using carbon monoxide (the source of carbonyl groups) and secondary amines (the source of amines); tertiary amines are a cheap and readily available raw material reagent. Utilizing the research results in photoredox catalysis in recent years, metal photosensitizers are used to carry out visible light-mediated amidation strategies for carboxylic acids and tertiary amines. Although the above methods have made significant progress, most of these methods still require precious metals and high-temperature heating, which are costly and cause environmental pollution.

The present invention aims to provide a method for directly converting tertiary amine into amide by using organic photocatalyst under mild conditions.

Summary of the invention

The object of the present invention is to provide a method for preparing amides from tertiary amines.

The object of the present invention is achieved by a method for preparing amides from tertiary amines, wherein an acid anhydride compound, a photocatalyst and a tertiary amine compound are dissolved in a dry organic solvent under an inert gas atmosphere, and a target amide compound is obtained by irradiating with blue light at room temperature. The general reaction formula is as follows:

;

Wherein, R is selected from any one of an alkyl group and a heterocycle; R ₁ , R ₂ , and R ₃ are independently selected from any one of an alkyl group and an aryl group;

The photocatalyst is 4CzIPN, [Ir(dF)(CF ₃ )ppy ₂ (dtbbpy)]PF ₆ , Mes-Acr ⁺ ClO ₄ , fac-Ir(ppy) ₃ or Eosin Y.

The present invention mixes anhydride compounds and tertiary amine compounds, adds a metal-free organic photocatalyst and irradiates the mixture under blue light to successfully prepare amide compounds. The photocatalyst used in the method of the present invention does not involve transition metals in the reaction, which not only reduces the cost required for the experiment, but also greatly reduces the production cost. The method of the present invention has strong substrate applicability, mild reaction conditions, high reaction selectivity, is green and environmentally friendly, and is low in price, and is worthy of promotion and application.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is a nuclear magnetic resonance H spectrum of the amide compound prepared in Example 1;

FIG2 is a C NMR spectrum of the amide compound prepared in Example 1;

FIG3 is a nuclear magnetic resonance H spectrum of the amide compound prepared in Example 2;

FIG4 is a C NMR spectrum of the amide compound prepared in Example 2;

FIG5 is a nuclear magnetic resonance H spectrum of the amide compound prepared in Example 3;

FIG6 is a C NMR spectrum of the amide compound prepared in Example 3;

FIG7 is a H NMR spectrum of the amide compound prepared in Example 4;

FIG8 is a C NMR spectrum of the amide compound prepared in Example 4;

FIG9 is a H NMR spectrum of the amide compound prepared in Example 5;

FIG10 is a C NMR spectrum of the amide compound prepared in Example 5;

FIG11 is a H NMR spectrum of the amide compound prepared in Example 6;

FIG12 is a C NMR spectrum of the amide compound prepared in Example 6;

FIG13 is a H NMR spectrum of the amide compound prepared in Example 7;

FIG14 is a C NMR spectrum of the amide compound prepared in Example 7;

FIG15 is a H NMR spectrum of the amide compound prepared in Example 8;

FIG16 is a C NMR spectrum of the amide compound prepared in Example 8;

FIG17 is a H NMR spectrum of the amide compound prepared in Example 9;

FIG. 18 is a C NMR spectrum of the amide compound prepared in Example 9.

DETAILED DESCRIPTION

The present invention is further described below in conjunction with the embodiments and drawings, but the present invention is not limited in any way. Any changes or substitutions made based on the teachings of the present invention belong to the protection scope of the present invention.

The present invention discloses a method for preparing amide from tertiary amine, which comprises dissolving an anhydride compound, a photocatalyst and a tertiary amine compound in a dry organic solvent under an inert gas atmosphere, and irradiating the compound with blue light at room temperature to obtain a target amide compound. The general reaction formula is as follows:

;

Wherein, R is selected from any one of an alkyl group and a heterocycle; R ₁ , R ₂ , and R ₃ are independently selected from any one of an alkyl group and an aryl group;

The photocatalyst is 4CzIPN, [Ir(dF)(CF ₃ )ppy ₂ (dtbbpy)]PF ₆ , Mes-Acr ⁺ ClO ₄ , fac-Ir(ppy) ₃ or Eosin Y.

The molar ratio of the acid anhydride compound, the photocatalyst and the tertiary amine compound is 1:0.01-0.05:2-5.

The inert gas is nitrogen or argon.

The dry organic solvent is one or more of dry acetonitrile, dry ethylene dichloride, dry methanol or dry 1,4-dioxane.

The blue light irradiation power is 20 W and the wavelength is 450-455nm.

Example 1

Under argon atmosphere, benzoic anhydride (42.5 mg, 0.2 mmol), triethylamine (40.5 mg, 0.4 mmol), Mes-Acr ⁺ ClO ₄ (2.5 mg, 0.006 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 2 ml of dry methanol was added. The mixture was irradiated under blue light and monitored by TLC until the benzoic anhydride was completely consumed. The molar ratio of benzoic anhydride, triethylamine, and Mes-Acr ⁺ ClO ₄ was 1:2:0.03. The residue was purified by silica gel column chromatography (using petroleum ether: ethyl acetate = 3:1 as eluent) to obtain the product N,N-diethylbenzamide (31.5 mg, 89% yield). ¹³ C NMR (101 MHz, Chloroform - ^d ) δ 171.6, 137.6, 129.4, 128.7, 126.6, 43.6, 39.6, 14.6, 13.3.

Example 2

Under argon atmosphere, p-toluic anhydride (50.8 mg, 0.2 mmol), triethylamine (83 ul, 0.6 mmol),

Eosin Y (2.6 mg, 0.004 mmol) was added to a Schlenk tube equipped with a magnetic stirrer, and 2 ml of dry acetonitrile was added. The mixture was irradiated under blue light and monitored by TLC until p-toluic anhydride was completely consumed. The molar ratio of p-toluic anhydride, triethylamine, and Eosin Y was 1:3:0.02. The residue was purified by silica gel column chromatography to obtain the product N,N-diethyl-4-methylbenzamide (37.8 mg, 99% yield). ¹ H NMR (400 MHz, Chloroform- d ) δ7.34 – 7.27 (m, 2H), 7.22 (d, J = 7.9 Hz, 2H), 3.57 (s, 2H), 3.30 (s, 2H), 2.40 (s, 3H), 1.20 (d, J = 47.7 Hz, 6H). ¹³ C NMR (101 MHz, Chloroform -d ) δ 171.3, 138.8, 134.0, 128.7, 126.1, 43.1, 39.0, 21.1, 14.0, 12.7.

Example 3

Under argon atmosphere, 4-naphthoic anhydride (65.4 mg, 0.2 mmol), triethylamine (83 ul, 0.6 mmol),

[Ir(dF)(CF ₃ )ppy ₂ (dtbbpy)]PF ₆ (4.5 mg, 0.004 mmol) was added to a Schlenk tube equipped with a magnetic stirrer, and 2 ml of dry acetonitrile was added. The mixture was irradiated under blue light and monitored by TLC until the naphthylic anhydride was completely consumed. The molar ratio of naphthylic anhydride, triethylamine, and [Ir(dF)(CF ₃ )ppy ₂ (dtbbpy)]PF ₆ was 1:3:0.02. The residue was purified by silica gel column chromatography to obtain the product N,N-diethyl-2-naphthamide (43.7 mg, 96% yield). ¹ H NMR (400 MHz, Chloroform- d ) δ 7.90 – 7.82 (m, 4H), 7.56 – 7.44 (m, 3H), 3.60 (d, J = 7.5 Hz, 2H), 3.32 – 3.26 (m, 2H), 1.29 (t, J = 7.2 Hz, 3H), 1.12 (t, J = 7.3 Hz, 3H). ¹³ CNMR (101 MHz, Chloroform- d ) δ 171.7, 135.0, 133.7, 133.1, 128.7 (d, J = 2.2Hz), 128.2, 127.2, 127.0, 126.1, 124.3 , 43.8, 39.7, 14.7, 13.4.

Example 4

Under argon atmosphere, 4-tert-butylbenzoic anhydride (67.7 mg, 0.2 mmol), triethylamine (113 ul, 0.8 mmol), Mes-Acr ⁺ ClO ₄ (1.6 mg, 0.004 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 2 ml of dry acetonitrile was added. The mixture was irradiated under blue light and monitored by TLC until 4-tert-butylbenzoic anhydride was completely consumed. The molar ratio of 4-tert-butylbenzoic anhydride, triethylamine, and Mes-Acr ⁺ ClO ₄ was 1:4:0.02. The residue was purified by silica gel column chromatography to obtain the product 4-(tert-butyl)-N,N-diethylbenzamide (30.9 mg, 75% yield). ¹ H NMR (400 MHz, Chloroform- d ) δ 7.42 – 7.35 (m, 2H), 7.32 – 7.28 (m, 2H), 3.53 (s, 2H), 3.28 (s, 2H), 1.31 (s, 9H), 1.23 (s, 3H), 1.12 (s, 3H) . ¹³ C NMR (101 MHz, Chloroform -d ) δ 170.5, 164.4, 161.9, 133.4, 133.3, 128.6, 128.6, 115.7, 115.5.

Example 5

Under argon atmosphere, 4-phenylbenzoic anhydride (75.6 mg, 0.2 mmol), triethylamine (83 ul, 0.6 mmol), Mes-Acr ⁺ ClO ₄ (1.6 mg, 0.004 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 2 ml of dry 1,4-dioxane was added. The mixture was irradiated under blue light and monitored by TLC until 4-phenylbenzoic anhydride was completely consumed. The molar ratio of 4-phenylbenzoic anhydride, triethylamine, and Mes-Acr ⁺ ClO ₄ was 1:3:0.02. The residue was purified by silica gel column chromatography to obtain the product N,N-diethyl-[1,1'-biphenyl]-4-carboxamide (43.5 mg, 86% yield). ¹ H NMR (400 MHz, Chloroform- d ) δ 7.65 – 7.56 (m, 4H), 7.49 – 7.41 (m, 4H), 7.39 – 7.34 (m,1H), 3.57 (d, J = 7.9 Hz, 2H), 3.34 – 3.28 (m, 2H), 1.2 7 (d, J = 7.5 Hz, 3H),1.14 (t, J = 7.1 Hz, 3H). ¹³ C NMR (101 MHz, Chloroform- d ) δ 171.2, 142.0, 140.4,136.1, 128.9, 127.7, 127.2, 126.9, 43.4, 39.3, 14.4, 13.0.

Example 6

Under argon atmosphere, 4-methoxybenzoic anhydride (57.3 mg, 0.2 mmol), triethylamine (83 ul, 0.6 mmol), Mes-Acr ⁺ ClO ₄ (1.6 mg, 0.004 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 2 ml of dry dichloroethane was added. The mixture was irradiated under blue light and monitored by TLC until 4-methoxybenzoic anhydride was completely consumed. The molar ratio of 4-methoxybenzoic anhydride, triethylamine, and Mes-Acr ⁺ ClO ₄ was 1:3:0.02. The residue was purified by silica gel column chromatography to obtain the product N,N-diethyl-4-methoxybenzamide (30.9 mg, 75% yield). ¹ H NMR (400 MHz, Chloroform- d ) δ 7.36 – 7.30 (m, 2H), 6.91 – 6.86 (m, 2H), 3.81 (s, 3H), 3.39 (d, J = 63.2 Hz, 4H), 1.16 (s, 6H). ¹³ C NMR (101 MHz, Ch loroform- d ) δ 173.1, 160.1, 131.3, 127.2, 116.9, 57.0, 47.7, 39.2, 36.9, 14.5, 13.0.

Example 7

Under argon atmosphere, thiophene anhydride (47.6 mg, 0.2 mmol), triethylamine (83 ul, 0.6 mmol), fac-Ir(ppy) ₃ (2.6 mg, 0.004 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 2 ml of dry acetonitrile was added. The mixture was irradiated under blue light and monitored by TLC until the thiophene anhydride was completely consumed. The molar ratio of thiophene anhydride, triethylamine, and fac-Ir(ppy) ₃ was 1:3:0.02. The residue was purified by silica gel column chromatography to obtain the product N,N-diethylthiophene-2-carboxamide (24.9 mg, 68% yield). ¹ H NMR (400 MHz, Chloroform- d ) δ 7.41 (dd, J =5.0, 1.1 Hz, 1H), 7.31 (dd, J = 3.6, 1.1 Hz, 1H), 7.02 (dd, J = 5.0, 3.7 Hz, 1H), 3.53 (q, J = 7.1 Hz, 4H), 1.24 (t, J = 7.1 Hz, 6H). ¹³ C NMR (101 MHz, Chloroform-d) δ 163.6, 138.1, 128.0, 127.7, 126.5, 49.7, 11.6.

Example 8

Under argon atmosphere, benzoic anhydride (45.2 mg, 0.2 mmol), tripropylamine (57.3 mg, 0.6 mmol), Mes-Acr ⁺ ClO ₄ (4.1 mg, 0.01 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 2 ml of dry acetonitrile was added. The mixture was irradiated under blue light and monitored by TLC until the benzoic anhydride was completely consumed. The molar ratio of benzoic anhydride, tripropylamine, and Mes-Acr ⁺ ClO ₄ was 1:3:0.05. The residue was purified by silica gel column chromatography to obtain the product N,N-dipropylbenzamide (37.6 mg, 92% yield). ¹ H NMR (400 MHz, Chloroform- d ) δ 7.38 – 7.31 (m, 5H), 3.44(t, J = 7.7 Hz, 2H), 3.14 (t, 1H), 1.72 – 1.62 (m, 2H), 1.50 (m, J = 6.7 Hz, 2H),0.96 (t, J = 7.4 Hz, 3H), 0.71 (t, J = 7.4 Hz, 3H). ¹³ C NMR (101 MHz, Chloroform- d )δ 172.2, 137.7, 129.4, 128.7, 126.8, 51.0, 46.6, 22.3, 21.1, 11.8, 11.4.

Embodiment 9

Under argon atmosphere, benzoic anhydride (45.2 mg, 0.2 mmol), N,N-dimethylaniline (72.7 mg, 0.6 mmol), Mes-Acr ⁺ ClO ₄ (4.1 mg, 0.01 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 2 ml of dry methanol was added. The mixture was irradiated under blue light and monitored by TLC until the benzoic anhydride was completely consumed. The molar ratio of benzoic anhydride, N,N-dimethylaniline, and Mes-Acr ⁺ ClO ₄ was 1:3:0.05. The residue was purified by silica gel column chromatography to obtain the product N-methyl-N-phenylbenzamide (21.1 mg, 50% yield). ¹ H NMR (400 MHz, Chloroform- d ) δ 7.33 –7.27 (m, 2H), 7.25 – 7.19 (m, 3H), 7.15 (ddd, J = 10.2, 8.2, 4.1 Hz, 3H), 7.07– 7.00 (m, 2H), 3.50 (d, J = 1.6 Hz, 3H). ¹³ C NMR (101 MHz, Chloroform- d ) δ170.5, 144.8, 135.7, 129.4, 129.0, 128.5, 127.5, 126.7,126.3, 38.2.

Claims (5)

1. A method for preparing amide from tertiary amine is characterized in that an anhydride compound, a photocatalyst and a tertiary amine compound are dissolved in a dry organic solvent under the atmosphere of inert gas, and the amide compound is obtained by adopting blue light irradiation at room temperature, wherein the reaction general formula is as follows:

；

Wherein R is selected from any one of alkyl and heterocycle; r ₁、R₂、R₃ is independently selected from any one of alkyl and aryl;

The photocatalyst is 4CzIPN,[Ir(dF)(CF₃)ppy₂(dtbbpy)]PF₆,Mes-Acr⁺ClO₄,fac-Ir(ppy)₃ or Eosin Y.

2. The method for producing an amide from a tertiary amine according to claim 1, wherein the mass ratio of the acid anhydride-based compound, the photocatalyst, and the tertiary amine-based compound is 1: 0.01-0.05: 2-5.

3. The method for producing amides from tertiary amines according to claim 1, characterized in that the inert gas is nitrogen or argon.

4. The method for producing an amide from a tertiary amine according to claim 1, wherein the dry organic solvent is one or more of dry acetonitrile, dry dichloroethane, dry methanol, and dry 1, 4-dioxane.

5. The method for producing amides from tertiary amines according to claim 1, characterized in that the blue light irradiation power is 20W and the wavelength is 450-455nm.