Method for preparing tartaric acid derivative through visible light catalysis of oxamic acid derivative decarboxylation

Abstract

The invention discloses a method for preparing a tartaric acid derivative through visible light catalysis of oxamic acid derivative decarboxylation, and belongs to the technical field of chemical synthesis.The method uses a photocatalyst, the oxamic acid derivative and alpha-keto ester react under photocatalysis to obtain the tartaric acid derivative at the medium yield, the process conditions are mild, operation is easy, and the method is suitable for industrial production. No stoichiometric oxidant is added, no oxygen participates in the whole synthesis process, the safety is high, and meanwhile, the generation of stoichiometric wastes is avoided. The synthesis method is different from the existing synthesis technology in the aspects of reaction types, initial raw materials, reverse synthesis broken bond selection and the like, and a new synthesis path is provided for the tartaric acid derivative.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for preparing a tartaric acid derivative by decarboxylation of an oxamic acid derivative catalyzed by visible light. Background Art

[0002] Hydroxymalonic acid, commonly known as tartaric acid, is an organic compound with carboxyl and hydroxyl functional groups. Tartaric acid and its derivatives are widely used, such as as reverse peptide substitutes (J.Med.Chem., 1998, 41, 339-345) and biodegradable surfactant synthesis building blocks (Polym.Adv.Technol.2001, 12, 697-710). The oxidation reaction between malonate and chemical oxidant (such as heavy metal oxidant or peroxy acid) is a classic method for preparing tartaric acid derivatives. Under the catalysis of transition metals, malonate can also react with oxygen to obtain malonate by introducing hydroxyl functional groups. The general chemical reaction formula is: However, the traditional methods have problems such as the generation of stoichiometric waste, the use of special catalysts or low yield. In view of the above problems, some new methods have been developed to synthesize tartaric acid derivatives. Carlos F. Marcos et al. reported that tartaric acid derivatives can be prepared by a continuous process of Passerini three-component reaction of glyoxylic acid esters or amides and zinc-catalyzed hydrolysis (Green Chem., 2006, 8, 787-789). The general chemical reaction formula is Akichika Itoh et al. found that β-ketoesters can react with oxygen under visible light irradiation to obtain tartaric acid derivatives through a tandem oxidation and rearrangement process (Org. Lett. 2010, 12, 1948-1951; RSC Adv. 2016, 6, 42596-42599). The general chemical reaction formula is: Nevertheless, these methods still have shortcomings in terms of raw material availability, ease of operation or reaction efficiency, so it is very necessary to develop new and efficient methods for synthesizing tartaric acid derivatives. Summary of the invention

[0003] In view of the problem that the existing technology mainly relies on some oxidation reactions when synthesizing tartaric acid derivatives, which will produce stoichiometric waste, and the use of oxygen in chemical production has certain safety risks, the present invention provides a method for preparing tartaric acid derivatives by decarboxylation of oxalic acid derivatives catalyzed by visible light, and intends to achieve efficient synthesis of tartaric acid derivatives through redox neutral reactions.

[0004] A method for preparing tartaric acid derivatives by decarboxylation of oxamate derivatives catalyzed by visible light comprises the following steps: mixing α-keto acid ester, oxamate derivative, photocatalyst and base in an organic solvent, removing oxygen, and synthesizing the tartaric acid derivative by free radical coupling reaction under visible light irradiation.

[0005] The method of the present invention uses oxalic acid derivatives and α-keto esters as starting materials, and synthesizes tartaric acid derivatives through a one-step redox neutral photocatalytic process. On the one hand, the photocatalyst is excited to oxidize the oxalic acid derivative to obtain an amide free radical intermediate. On the other hand, the α-keto ester is reduced by a reduced photocatalyst to generate an α-hydroxyl free radical intermediate, and the above two free radicals are coupled to construct a CC (CO) bond to achieve the synthesis of tartaric acid derivatives.

[0006] The free radical coupling reaction is as follows:

[0007]

[0008] Among them, R 1 is selected from Ph or 4-Cl-Ph; R 2 Selected from Et or Me; R 3 Selected from N( n Pr)2 or N(Et)2.

[0009] The molar ratio of the α-keto acid ester to the oxamic acid derivative is 3:2.

[0010] The amount of the photocatalyst is 2 mol% of the oxamic acid derivative.

[0011] The photocatalyst is selected from 4CzIPN, 3DPA2FBN or [Ir(dtbbpy)(ppy)2]PF6; the chemical structural formula of the photocatalyst is:

[0012]

[0013] The molar ratio of the base to the oxamic acid derivative is 2:1.

[0014] The base is cesium carbonate.

[0015] The organic solvent is selected from acetonitrile or dichloromethane.

[0016] The free radical coupling reaction time is 24h, and the temperature is 25-55°C; the temperature of the free radical coupling reaction is preferably 35°C.

[0017] The present invention realizes photocatalysis by placing Kessil LED lamps on one side or both sides of the reaction device, and controls the reaction temperature by adjusting the number of Kessil LED lamps and their positional relationship with the reaction device.

[0018] Compared with the prior art, the present invention has the following advantages and technical effects:

[0019] The present invention uses a photocatalyst, and under the action of photocatalysis, an oxamic acid derivative reacts with an α-keto acid ester to obtain a tartaric acid derivative with a medium yield. The process has mild conditions and is simple to operate. No stoichiometric oxidant needs to be added. No oxygen is involved in the entire synthesis process, and the safety is high. At the same time, stoichiometric waste is avoided. The present invention is different from the existing synthesis technology in terms of reaction type, starting material, and reverse synthesis bond breaking selection, and provides a new synthesis route for tartaric acid derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0021] Figure 1 The schematic diagram of the chemical principle of synthesizing tartaric acid derivatives of the present invention;

[0022] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the tartaric acid derivative III-a synthesized in Example 1;

[0023] Figure 3 This is the H NMR spectrum of the tartaric acid derivative III-b synthesized in Example 2;

[0024] Figure 4 This is the hydrogen nuclear magnetic resonance spectrum of the tartaric acid derivative III-c synthesized in Example 3;

[0025] Figure 5 This is the hydrogen nuclear magnetic resonance spectrum of the tartaric acid derivative III-d synthesized in Example 4. DETAILED DESCRIPTION

[0026] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0027] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0028] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0029] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present application description and examples are exemplary only.

[0030] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0031] The present invention uses oxalic acid derivatives and α-keto esters as starting materials to synthesize tartaric acid derivatives through a one-step redox neutral photocatalytic process. On the one hand, the photocatalyst is excited to oxidize the oxalic acid derivative to obtain an amide free radical intermediate. On the other hand, the α-keto ester is reduced by a reduced photocatalyst to generate an α-hydroxyl free radical intermediate. The above two free radicals are coupled to construct a CC (CO) bond to achieve the synthesis of tartaric acid derivatives. Figure 1 The figure is a schematic diagram of the chemical principle of synthesizing tartaric acid derivatives of the present invention.

[0032] In some embodiments of the present invention, the route for synthesizing tartaric acid derivatives is as follows:

[0033]

[0034] The α-keto esters, photocatalysts, and bases used in the embodiments of the present invention are all obtained through conventional commercial channels, and the oxamate derivatives can be synthesized in one step according to the literature method (Org. Lett. 2023, 25, 1829-1833).

[0035] Example 1

[0036] α-ketoester II-a (0.3 mmol, 1.5 eq), oxamate derivative Ia (0.2 mmol, 1.0 eq), 3DPA2FBN (0.004 mmol, 2.6 mg, 2 mol%), Cs2CO3 (0.4 mmol, 130.3 mg, 2.0 eq) and acetonitrile (4 mL) were added to a 20 mL glass bottle equipped with a stirrer. After the glass bottle was sealed with a polytetrafluoroethylene septum, it was degassed using a freeze-pump-thaw method. Two 440 nm Kessil LED lamps were placed 7 cm away from the glass bottle (the two Kessil LED lamps were located on both sides of the glass bottle, forming a three-point line), and a fan was placed 10 cm above the bottle to keep the internal temperature of the glass bottle at 35°C ± 1°C. After the reaction mixture was stirred and irradiated for 24 h, it was directly concentrated under reduced pressure and separated by column chromatography (petroleum ether / ethyl acetate = 10:1) to obtain tartaric acid derivative III-a (37.0 mg, 42% NMR yield, yellow oil).

[0037] The H NMR spectrum of the tartaric acid derivative III-a prepared in Example 1 is shown in Figure 2 , the hydrogen spectrum data are as follows:

[0038] 1 H NMR (400MHz, CDCl3) δ7.54-7.29(m,5H),5.03(s,1H),4.35-4.15(m,2H),3.39-3.32(m,1H),3.18-3.11(m,1H),3.08-3.01(m,1H),2.96-2 .88(m,1H),1.64-1.53(m,2H),1.28-1.21(m,1H),1.25(t,J=7.1Hz,3H),1.10-1.00(m,1H),0.89(t,J=7.4Hz,3H),0.53(t,J=7.4Hz,3H).

[0039] Example 2

[0040] α-ketoester II-b (0.3 mmol, 1.5 eq), oxamate derivative Ia (0.2 mmol, 1.0 eq), 3DPA2FBN (0.004 mmol, 2.6 mg, 2 mol%), Cs2CO3 (0.4 mmol, 130.3 mg, 2.0 eq) and acetonitrile (4 mL) were added to a 20 mL glass bottle equipped with a stirrer. After the glass bottle was sealed with a polytetrafluoroethylene septum, it was degassed using a freeze-pump-thaw method. Two 440 nm Kessil LED lamps were placed 7 cm away from the glass bottle (the two Kessil LED lamps were located on both sides of the glass bottle, forming a three-point line), and a fan was placed 10 cm above the bottle to keep the internal temperature of the glass bottle at 35°C ± 1°C. After the reaction mixture was stirred and irradiated for 24 h, it was directly concentrated under reduced pressure and separated by column chromatography (petroleum ether / ethyl acetate = 5:1) to obtain a tartaric acid derivative III-b (43.7 mg, 55%, yellow oil).

[0041] The H NMR spectrum of the tartaric acid derivative III-b prepared in Example 2 is shown in Figure 3 , the hydrogen spectrum data are as follows:

[0042] 1 H NMR (400MHz, CDCl3) δ7.56-7.27(m,5H),5.03(s,1H),3.79(s,3H),3.43-3.27(m,1H),3.20-3.09(m,1H),3.09-2.99(m,1H) ,2.94-2.86(m,1H),1.70-1.48(m,2H),1.36-1.18(m,1H),1.15-0.98(m,1H),0.88(t,J=7.4Hz,3H),0.54(t,J=7.4Hz,3H).

[0043] Example 3

[0044] α-ketoester II-c (0.3 mmol, 1.5 eq), oxamate derivative Ia (0.2 mmol, 1.0 eq), 3DPA2FBN (0.004 mmol, 2.6 mg, 2 mol%), Cs2CO3 (0.4 mmol, 130.3 mg, 2.0 eq) and acetonitrile (4 mL) were added to a 20 mL glass bottle equipped with a stirrer. After the glass bottle was sealed with a polytetrafluoroethylene septum, it was degassed using the freeze-pump-thaw method. Two 440 nm Kessil LED lamps were placed 7 cm away from the glass bottle (the two Kessil LED lamps were located on both sides of the glass bottle, forming a three-point line), and a fan was placed 10 cm above the bottle to keep the internal temperature of the glass bottle at 35°C ± 1°C. After the reaction mixture was stirred and irradiated for 2 h, it was directly concentrated under reduced pressure and separated by column chromatography (petroleum ether / ethyl acetate = 10:1) to obtain tartaric acid derivative III-c (39.8 mg, 40% NMR yield, yellow oil).

[0045] The H NMR spectrum of the tartaric acid derivative III-c prepared in Example 3 is shown in Figure 4 , the hydrogen spectrum data are as follows:

[0046] 1 H NMR (400MHz, CDCl3) δ7.49-7.30(m,5H),4.97(s,1H),4.33-4.12(m,2H),3.38-3.31(m,1H),3.15-3.08(m,1H),3.07-2.99(m,1H),2.92-2 .84(m,1H),1.63-1.50(m,2H),1.39-1.22(m,1H),1.23(t,J=7.2Hz,3H),1.16-1.07(m,1H),0.87(t,J=7.4Hz,3H),0.58(t,J=7.4Hz,3H).

[0047] Example 4

[0048] α-ketoester II-a (0.3 mmol, 1.5 eq), oxamate derivative Ib (0.2 mmol, 1.0 eq), 3DPA2FBN (0.004 mmol, 2.6 mg, 2 mol%), Cs2CO3 (0.4 mmol, 130.3 mg, 2.0 eq) and acetonitrile (4 mL) were added to a 20 mL glass bottle equipped with a stirrer. After the glass bottle was sealed with a polytetrafluoroethylene septum, it was degassed using a freeze-pump-thaw method. Two 440 nm Kessil LED lamps were placed 7 cm away from the glass bottle (the two Kessil LED lamps were located on both sides of the glass bottle, forming a three-point line), and a fan was placed 10 cm above the bottle to keep the internal temperature of the glass bottle at 35°C ± 1°C. After the reaction mixture was stirred and irradiated for 24 h, it was directly concentrated under reduced pressure and separated by column chromatography (petroleum ether / ethyl acetate = 5:1) to obtain a tartaric acid derivative III-d (36.2 mg, 50% NMR yield, yellow oil).

[0049] The H NMR spectrum of the tartaric acid derivative III-d prepared in Example 4 is shown in Figure 5 , the hydrogen spectrum data are as follows:

[0050] 1 H NMR (400MHz, CDCl3) δ7.52-7.30(m,5H),5.03(s,1H),4.34-4.15(m,2H),3.51-3.42(m,1H),3.30-3.22(m,1H ),3.21-3.14(m,1H),3.08-3.01(m,1H),1.25(t,J=7.0Hz,3H),1.15(t,J=7.0Hz,3H),0.76(t,J=7.0Hz,3H).

[0051] Example 5

[0052] α-ketoester II-a (0.3 mmol, 1.5 eq), oxamate derivative Ia (0.2 mmol, 1.0 eq), 4CzIPN (0.004 mmol, 3.2 mg, 2 mol%), Cs2CO3 (0.4 mmol, 130.3 mg, 2.0 eq) and acetonitrile (4 mL) were added to a 20 mL glass bottle equipped with a stirrer. After the glass bottle was sealed with a polytetrafluoroethylene septum, it was degassed using a freeze-pump-thaw method. Two 440 nm Kessil LED lamps were placed 7 cm away from the glass bottle (the two Kessil LED lamps were located on both sides of the glass bottle, forming a three-point line), and a fan was placed 10 cm above the bottle to keep the internal temperature of the glass bottle at 35°C ± 1°C. After the reaction mixture was stirred and irradiated for 24 h, it was directly concentrated under reduced pressure and separated by column chromatography (petroleum ether / ethyl acetate = 10:1) to obtain tartaric acid derivative III-a (28.0 mg, 32% NMR yield, yellow oil).

[0053] Example 6

[0054] Into a 20 mL glass bottle equipped with a stirrer, α-ketoester II-a (0.3 mmol, 1.5 eq), oxalic acid derivative Ia (0.2 mmol, 1.0 eq), Ir(dtbbpy)(ppy)2]PF6 (0.004 mmol, 3.7 mg, 2 mol%), Cs2CO3 (0.4 mmol, 130.3 mg, 2.0 eq) and acetonitrile (4 mL) were added in sequence. After the glass bottle was sealed with a polytetrafluoroethylene septum, it was degassed using the freeze-pump-thaw method. Two 440nm Kessil LED lamps were placed 7 cm away from the glass bottle (the two Kessil LED lamps were located on both sides of the glass bottle, forming a straight line), and a fan was placed 10 cm above the bottle to maintain the internal temperature of the glass bottle at 35°C ± 1°C. The reaction mixture was stirred and irradiated for 24 h, then directly concentrated under reduced pressure and separated by column chromatography (petroleum ether / ethyl acetate = 10:1) to obtain tartaric acid derivative III-a (34.4 mg, 39% NMR yield, yellow oil).

[0055] Example 7

[0056] α-ketoester II-a (0.3 mmol, 1.5 eq), oxamate derivative Ia (0.2 mmol, 1.0 eq), 3DPA2FBN (0.004 mmol, 2.6 mg, 2 mol%), Cs2CO3 (0.4 mmol, 130.3 mg, 2.0 eq) and acetonitrile (4 mL) were added to a 20 mL glass bottle equipped with a stirrer. After the glass bottle was sealed with a polytetrafluoroethylene septum, it was degassed using a freeze-pump-thaw method. Two 440 nm Kessil LED lamps were placed 7 cm away from the glass bottle (the two Kessil LED lamps were located on both sides of the glass bottle, forming a three-point line), so that the internal temperature of the glass bottle was maintained at 55°C ± 1°C. After the reaction mixture was stirred and irradiated for 24 h, it was directly concentrated under reduced pressure and separated by column chromatography (petroleum ether / ethyl acetate = 10:1) to obtain tartaric acid derivative III-a (31.7 mg, 36% NMR yield, yellow oil).

[0057] Example 8

[0058] α-ketoester II-a (0.3 mmol, 1.5 eq), oxamate derivative Ia (0.2 mmol, 1.0 eq), 3DPA2FBN (0.004 mmol, 2.6 mg, 2 mol%), Cs2CO3 (0.4 mmol, 130.3 mg, 2.0 eq) and acetonitrile (4 mL) were added to a 20 mL glass bottle equipped with a stirrer. After the glass bottle was sealed with a polytetrafluoroethylene septum, it was degassed using a freeze-pump-thaw method. A 440 nm Kessil LED lamp was placed 7 cm away from the glass bottle, and a fan was placed 10 cm above the bottle to keep the internal temperature of the glass bottle at 25°C ± 1°C. After the reaction mixture was stirred and irradiated for 24 h, it was directly concentrated under reduced pressure and separated by column chromatography (petroleum ether / ethyl acetate = 10:1) to obtain a tartaric acid derivative III-a (28.2 mg, 32% NMR yield, yellow oil).

[0059] Comparative Example 1

[0060] α-ketoester II-a (0.3 mmol, 1.5 eq), oxalic acid derivative Ia (0.2 mmol, 1.0 eq), (Ir{dF(CF3)ppy}2(dtbpy))PF6 (0.004 mmol, 4.5 mg, 2 mol%), Cs2CO3 (0.4 mmol, 130.3 mg, 2.0 eq) and acetonitrile (4 mL) were added to a 20 mL glass bottle equipped with a stirrer. After the glass bottle was sealed with a polytetrafluoroethylene septum, it was degassed using a freeze-pump-thaw method. Two 440 nm Kessil LED lamps were placed 7 cm away from the glass bottle, and a fan was placed 10 cm above the bottle to keep the internal temperature of the glass bottle at 35°C ± 1°C. After the reaction mixture was stirred and irradiated for 24 h, it was directly concentrated under reduced pressure and separated by column chromatography (petroleum ether / ethyl acetate = 10:1) to obtain a tartaric acid derivative III-a (9.69 mg, 11% NMR yield, yellow oil).

[0061] Comparative Example 2

[0062] α-ketoester II-a (0.3 mmol, 1.5 eq), oxamate derivative Ia (0.2 mmol, 1.0 eq), 3DPA2FBN (0.004 mmol, 2.6 mg, 2 mol%), CsF (0.4 mmol, 60.8 mg, 2.0 eq) and acetonitrile (4 mL) were added to a 20 mL glass bottle equipped with a stirrer. After the glass bottle was sealed with a polytetrafluoroethylene septum, it was degassed using a freeze-pump-thaw method. Two 440 nm Kessil LED lamps were placed 7 cm away from the glass bottle, and a fan was placed 10 cm above the bottle to keep the internal temperature of the glass bottle at 35°C ± 1°C. After the reaction mixture was stirred and irradiated for 24 h, it was directly concentrated under reduced pressure and separated by column chromatography (petroleum ether / ethyl acetate = 10:1) to obtain a tartaric acid derivative III-a (4.4 mg, 5% NMR yield, yellow oil).

[0063] The above are only preferred specific implementations of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims

1. A method for preparing tartaric acid derivatives by decarboxylation of oxamic acid derivatives catalyzed by visible light, characterized in that: The following steps are involved: Alpha-keto acid ester, oxamic acid derivative, photocatalyst and base are mixed in an organic solvent, and after removing oxygen, tartaric acid derivative is synthesized through free radical coupling reaction under visible light irradiation.

2. The method for preparing tartaric acid derivatives by decarboxylation of oxamic acid derivatives catalyzed by visible light according to claim 1, characterized in that: The molar ratio of the α-keto acid ester to the oxamic acid derivative is 3:

2.

3. The method for preparing tartaric acid derivatives by decarboxylation of oxamic acid derivatives catalyzed by visible light according to claim 1, characterized in that: The amount of the photocatalyst is 2 mol% of the oxamic acid derivative.

4. The method for preparing tartaric acid derivatives by decarboxylation of oxamic acid derivatives catalyzed by visible light according to claim 3, characterized in that: The photocatalyst is selected from 4CzIPN, 3DPA2FBN or [Ir(dtbbpy)(ppy)2]PF6.

5. The method for preparing tartaric acid derivatives by decarboxylation of oxamic acid derivatives catalyzed by visible light according to claim 1, characterized in that: The molar ratio of the base to the oxamic acid derivative is 2:

1.

6. The method for preparing tartaric acid derivatives by decarboxylation of oxamic acid derivatives catalyzed by visible light according to claim 1, characterized in that: The base is cesium carbonate.

7. The method for preparing tartaric acid derivatives by decarboxylation of oxamic acid derivatives catalyzed by visible light according to claim 1, characterized in that: The organic solvent is selected from acetonitrile or dichloromethane.

8. The method for preparing tartaric acid derivatives by decarboxylation of oxamic acid derivatives catalyzed by visible light according to claim 1, characterized in that: The free radical coupling reaction time is 24 hours and the temperature is 25-55°C.

9. The method for preparing tartaric acid derivatives by decarboxylation of oxamic acid derivatives catalyzed by visible light according to claim 8, characterized in that: The temperature of the free radical coupling reaction was 35°C.

Images