A method for synthesizing isochroman-1,4-dione containing germanium group

Abstract

Allochran-1,4-diketones are a class of important benzo[a]oxo-heterocyclic compounds with unique structures and wide applications, playing a crucial role in organic synthesis, medicinal chemistry, and natural product chemistry. They form the core structure of many bioactive natural products. Organogermanium compounds, with their moderate reactivity, good biocompatibility, and structural tunability, have become key frameworks connecting organic synthesis, drug development, and functional materials. This invention patent realizes a method for the synthesis of germanium-containing allochran-1,4-diketones under mild conditions. This method features mild reaction conditions and simple operation, providing an efficient synthetic method for germanium-substituted allochran-1,4-diketones containing quaternary carbon centers.

Description

Technical Field

[0001] This invention relates to compound preparation, belonging to the field of organic compound synthesis. Specifically, it relates to a method for synthesizing germanium-based isochromic 1,4-dione under mild conditions. Background Technology

[0002] Isochran-1,4-diones are a class of important benzo[a]oxane heterocyclic compounds with unique structures and wide applications, playing a vital role in organic synthetic chemistry, medicinal chemistry, and natural product chemistry. They form the core skeleton of many bioactive natural products, such as the antifungal metabolite monocerin and the antioxidant molecule Norbergenin, exhibiting various pharmacological activities including antimalarial, antioxidant, and antibacterial effects. As a key synthetic intermediate, they can be efficiently converted into the 1,4-naphthoquinone skeleton, making them an important precursor for the preparation of clinical drugs such as the antiparasitic drug atovaquinone. Their 3-substituted derivatives, especially those containing a quaternary carbon center, have extremely high application value in drug molecule design and structure-activity relationship optimization due to their unique spatial structure and metabolic stability (Equation 1).

[0003]

[0004] On the other hand, organogermanium compounds, as important members of group 14 organic molecules, have become a key framework connecting organic synthesis, drug development, and functional materials due to their moderate reactivity, good biocompatibility, and structural tunability. They not only enrich synthetic methodologies as novel coupling reagents but also optimize the lipophilicity and metabolic properties of drug molecules through structural modification, demonstrating irreplaceable research and application value in the development of innovative drugs and advanced functional materials.

[0005] Therefore, developing mild, efficient, and universally applicable methods to synthesize germanium-substituted isochromic 1,4-diones, especially derivatives containing quaternary carbon centers, has significant practical value. Summary of the Invention

[0006] Given the importance of isochorium-1,4-dione and organogermanium compounds in organic chemistry, medicinal chemistry and materials science, this invention patent realizes a method for synthesizing germanium-containing isochorium-1,4-dione under mild conditions.

[0007] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: a method for synthesizing germanium-containing heterochromatic 1,4-dione, characterized in that: using ortho-substituted acryloylbenzoic acid and triphenyl germanium hydrogenation as raw materials, under the promotion of tris(2,2'-bipyridine)ruthenium tetrafluoroborate photosensitizer and tert-butyl peroxide, the reaction is carried out in acetonitrile (CH3CN) solvent at room temperature under 420 nm light for 6 hours, to obtain a class of germanium-substituted heterochromatic 1,4-diones with the general formula:

[0008]

[0009] Where R represents methyl, ethyl, propyl, or butyl.

[0010] Preferably, the amount of triphenylgermanium hydrogenation is twice the amount of acryloylbenzoic acid.

[0011] Preferably, the amount of tris(2,2'-bipyridine)ruthenium tetrafluoroborate is 3% of the amount of acryloylbenzoic acid.

[0012] Preferably, the amount of tert-butyl peroxide is twice the amount of acryloylbenzoic acid.

[0013] This method offers mild reaction conditions and simple operation. It provides an efficient synthetic route for germanium-substituted isochromatic 1,4-diones containing quaternary carbon centers. It has significant application value in organic chemistry, medicinal chemistry, and materials science. Detailed Implementation

[0014] The technical solution of the present invention will be further described below through specific embodiments:

[0015] Example 1

[0016] The reaction formula for this embodiment is as follows:

[0017]

[0018] (1) Acryloylbenzoic acid (0.1 mmol, 1.0 equiv), triphenylgermanium hydrogen (0.2 mmol, 2.0 equiv), and (2,2'-bipyridine)ruthenium tetrafluoroborate (3 mol%) were added to a sealed reaction tube with a side arm and a magnetic inlet under air. The reaction tube was evacuated and then filled with nitrogen. 1 mL of acetonitrile was added to the reaction tube and the reaction was carried out at room temperature under 420 nm light for 6 hours.

[0019] (2) The solvent in the organic phase obtained in step (1) was evaporated to obtain the crude product. The crude product was then purified by silica gel column chromatography. The separation yield was 62% and the product purity was greater than 99%.

[0020] Example 2

[0021] The reaction formula for this embodiment is as follows:

[0022]

[0023] (1) Acryloylbenzoic acid (0.1 mmol, 1.0 equiv), triphenylgermanium hydrogen (0.2 mmol, 2.0 equiv), and (2,2'-bipyridine)ruthenium tetrafluoroborate (3 mol%) were added to a sealed reaction tube with a side arm and a magnetic inlet under air. The reaction tube was evacuated and then filled with nitrogen. 1 mL of acetonitrile was added to the reaction tube and the reaction was carried out at room temperature under 420 nm light for 6 hours.

[0024] (2) The solvent in the organic phase obtained in step (1) was evaporated to obtain the crude product. The crude product was then purified by silica gel column chromatography with a separation yield of 60% and a product purity of more than 99%.

[0025] Example 3

[0026] The reaction formula for this embodiment is as follows:

[0027]

[0028] (1) Acryloylbenzoic acid (0.1 mmol, 1.0 equiv), triphenylgermanium hydrogen (0.2 mmol, 2.0 equiv), and (2,2'-bipyridine)ruthenium tetrafluoroborate (3 mol%) were added to a sealed reaction tube with a side arm and a magnetic inlet under air. The reaction tube was evacuated and then filled with nitrogen. 1 mL of acetonitrile was added to the reaction tube and the reaction was carried out at room temperature under 420 nm light for 6 hours.

[0029] (2) The solvent in the organic phase obtained in step (1) was evaporated to obtain the crude product. The crude product was then purified by silica gel column chromatography. The separation yield was 65% and the product purity was greater than 99%.

[0030] Example 4

[0031] The reaction formula for this embodiment is as follows:

[0032]

[0033] (1) Acryloylbenzoic acid (0.1 mmol, 1.0 equiv), triphenylgermanium hydrogen (0.2 mmol, 2.0 equiv), and (2,2'-bipyridine)ruthenium tetrafluoroborate (3 mol%) were added to a sealed reaction tube with a side arm and a magnetic inlet under air. The reaction tube was evacuated and then filled with nitrogen. 1 mL of acetonitrile was added to the reaction tube and the reaction was carried out at room temperature under 420 nm light for 6 hours.

[0034] (2) The solvent in the organic phase obtained in step (1) was evaporated to obtain the crude product. The crude product was then purified by silica gel column chromatography. The separation yield was 58%, and the product purity was greater than 99%.

[0035] The amounts of each substance used and the reaction conditions were experimentally extended to the examples to demonstrate that the technical solution of the present invention has good functional group compatibility.

[0036] The present invention has been described in detail above. The above description is only an embodiment of the present invention and should not be construed as limiting the scope of this application. All equivalent changes and modifications made within the scope of this application should still fall within the scope of the present invention.

[0037] Attached Figure Description

[0038] Figure 1 The proton NMR spectrum of compound 1 prepared in this invention;

[0039] Figure 2 The carbon NMR spectrum of compound 1 prepared in this invention;

[0040] Figure 3 The proton NMR spectrum of compound 3 prepared in this invention;

[0041] Figure 4 The carbon NMR spectrum of compound 3 prepared in this invention.

Claims

1. A method for synthesizing a germanium-containing heterochromatic 1,4-dione, characterized in that: Using ortho-substituted acryloylbenzoic acid and triphenyl germanium hydrogenate as raw materials, and under the photosensitizer of tris(2,2'-bipyridine)ruthenium tetrafluoroborate and the promoter of tert-butyl peroxide, the reaction was carried out in acetonitrile solvent at room temperature under 420 nm light for 6 hours to obtain a class of heterochromatic 1,4-dione compounds with the general formula: Where R represents methyl, ethyl, propyl, or butyl.

2. The method for synthesizing a germanium-containing heterochromatic 1,4-dione according to claim 1, wherein the amount of triphenylhydrogermanium is twice the amount of acryloylbenzoic acid; the amount of tris(2,2'-bipyridine)ruthenium tetrafluoroborate is 3% of the amount of acryloylbenzoic acid; and the amount of tert-butyl peroxyacetate is twice the amount of acryloylbenzoic acid.

Images