Preparation method of a 4H-benzo[d][1,3]oxazin-4-one compound

Abstract

The present invention discloses a preparation method of 4H-benzo[d][1,3]oxazin-4-one compounds, comprising the following steps: mixing an acyl aniline compound or an aniline compound, a rhodium catalyst, an oxidant, and an additive in a molar ratio of 1:(0.001-0.1):(0.1-5):(0-2) with dichloroethane to make the molar concentration of the acyl aniline 0.05-0.5 M, and reacting at 50-120 °C for 12-30 h under a carbon monoxide gas atmosphere; separating and purifying to obtain the 4H-benzo[d][1,3]oxazin-4-one compound. The present invention has the characteristics of simplicity, high efficiency, and good functional group tolerance.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical engineering, and particularly relates to a preparation method of 4H-benzo[d][1,3]oxazin-4-one compounds. Background Art

[0002] Benzoxazinones exist in many compounds with pharmacological and biological activities. For example, antibacterial agents, inhibitors of many proteases, antituberculosis drugs, and potential drugs for treating HIV. Additionally, it is also a starting material for constructing many important nitrogen heterocyclic compounds in synthetic chemistry, such as quinazolinone compounds, isocoumarin derivatives, and so on.

[0003] Currently, there are mainly two known synthesis methods for 4H-benzo[d][1,3]oxazin-4-one: the first is the cyclization of anthranilic acid and its derivatives N-acylanthranilic acid and acid anhydrides; the other is the cyclization of o-haloarylanilines or amides catalyzed by transition metals. However, these two methods either have difficult-to-prepare raw materials or require substrate pre-activation steps, which greatly limit their applications. Summary of the Invention

[0004] The purpose of the present invention is to provide a preparation method of 4H-benzo[d][1,3]oxazin-4-one compounds that is simple, efficient, and has good functional group tolerance, overcoming the above-mentioned drawbacks.

[0005] The purpose of the present invention and the solution to its main technical problems are achieved by adopting the following technical solutions:

[0006] A preparation method of 4H-benzo[d][1,3]oxazin-4-one compounds of the present invention includes the following steps:

[0007] (1) Mix an aniline compound or an acyl aniline compound, a rhodium catalyst, an oxidant, and an additive in a molar ratio of 1:(0.001 - 0.1):(0.1 - 5):(0 - 2), and mix with dichloroethane to make the acyl aniline molar concentration 0.05 - 0.5 M, and react at 50 - 120 °C for 12 - 30 h under a carbon monoxide gas atmosphere;

[0008] (2) Separate and purify to obtain 4H-benzo[d][1,3]oxazin-4-one compounds.

[0009] In the above-mentioned preparation method of 4H-benzo[d][1,3]oxazin-4-one compounds, the acyl aniline compound has the following structural formula:

[0010]

[0011] Among them, R1 is an aryl group, a substituted aryl group, a fused-ring aryl group, or a substituted fused-ring aryl group. R2 is an alkyl group, a cycloalkyl group, an amino group, or an aryl group;

[0012] The aniline compound has the following structural formula:

[0013]

[0014] Wherein, R is an aryl group, a substituted aryl group, a fused-ring aryl group or a substituted fused-ring aryl group;

[0015] The rhodium catalyst is [RhCp*Cl2] or [RhCp*(MeCN)3][SbF6]2;

[0016] The oxidant is silver acetate, silver pivalate;

[0017] The additive is AgNTf2, acetic anhydride.

[0018] The preparation method of the above-mentioned 4H-benzo[d][1,3]oxazin-4-one compound, wherein: preferably, the molar ratio of N-trimethylacetanilide, rhodium catalyst, oxidant, and additive is 1:0.1:3:1.5.

[0019] The preparation method of the above-mentioned 4H-benzo[d][1,3]oxazin-4-one compound, wherein: the molar concentration of acetanilide or aniline is 0.1 M.

[0020] The preparation method of the above-mentioned 4H-benzo[d][1,3]oxazin-4-one compound, wherein: the reaction temperature is 90-100 °C.

[0021] The preparation method of the above-mentioned 4H-benzo[d][1,3]oxazin-4-one compound, wherein: preferably, the catalyst is [RhCp*(MeCN)3][SbF6].

[0022] The preparation method of the above-mentioned 4H-benzo[d][1,3]oxazin-4-one compound, wherein: the oxidant is silver acetate.

[0023] The preparation method of the above-mentioned 4H-benzo[d][1,3]oxazin-4-one compound, wherein: the additive is acetic anhydride.

[0024] Compared with the prior art, the present invention has obvious advantages and beneficial effects. As can be seen from the above technical solutions, the present invention uses amide as a directing group (which can be generated in situ) to assist the direct C-H functionalization, which has the characteristics of high efficiency, excellent site selectivity and atom economy. The direct C-H functionalization is catalyzed by rhodium metal to directly generate benzoxazinone compounds from aniline or amide derivatives in one step. The present invention has the advantages of simplicity, high efficiency and good functional group tolerance. The 4H-benzo[d][1,3]oxazin-4-one hydrolyzes itself in the presence of water to obtain o-aminocarboxylic acid derivatives, which have a wide range of applications in the fields of medicine and materials and are excellent organic synthesis intermediates. Detailed Description of the Invention

[0025] The following will describe in detail the specific implementation manner, structure and characteristics of a preparation method of a 4H-benzo[d][1,3]oxazin-4-one compound according to the present invention with reference to the accompanying drawings and preferred embodiments.

[0026] Example 1:

[0027] A preparation method of a 4H-benzo[d][1,3]oxazin-4-one compound of the present invention includes:

[0028] Add N-trimethylacetanilide (0.1 mmol), [Cp * Rh(MeCN)3][SbF6]2 (10 mol%), silver acetate (0.3 mmol), and acetic anhydride (0.05 mmol) into a dry 10 mL reaction tube in sequence. Add 1 mL of dichloroethane solution, and use a carbon monoxide balloon to pump and replace the gas three times. Stir and react at 95 °C in an oil bath for 24 h. After the reaction is completed, purify by silica gel column chromatography (the eluent is PE / EA = 20:1 (v / v)) to obtain a white solid 2-(tert-butyl)-4H-benzo[d][1,3]oxazin-4-one (17.1 mg, 84% yield). The structure of the product is as follows:

[0029]

[0030] The structure characterization data is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 8.19 (d, J = 7.9 Hz, 1H), 7.78 (t, J = 7.7 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 1.40 (d, J = 0.6 Hz, 9H). 1313C NMR (125 MHz, Chloroform-d) δ 168.2, 160.1, 146.5, 136.2, 128.2, 128.0, 126.9, 116.8, 37.9, 27.7. HRMS (ESI) m / z:

[0031] [M+H]+ Calcd. for C 12 H 14 NO2 204.1019 found 204.1016

[0032] Example 2:

[0033] A preparation method of a 4H-benzo[d][1,3]oxazin-4-one compound of the present invention includes:

[0034] 4-Methyl-N-trimethylacetanilide (0.1 mmol), [Cp * Rh(MeCN)3][SbF6]2 (10 mol%), silver acetate (0.3 mmol), and acetic anhydride (0.05 mmol) were successively added to a dry 10 mL reaction tube. 1 mL of dichloroethane solution was added, and the mixture was evacuated and replaced with carbon monoxide gas three times using a carbon monoxide balloon. The reaction was stirred at 95 °C in an oil bath for 24 h. After the reaction was completed, Et3N (0.1 mmol, 13.5 μL) was added, and the product was purified by silica gel column chromatography (eluent: PE / EA = 20:1 (v / v)) to obtain a white solid 2-(tert-butyl)-6-methyl-4H-benzo[d][1,3]oxazin-4-one (19.3 mg, 89% yield). The structure of the product is as follows:

[0035]

[0036] Structure characterization is as follows: 1H NMR (500 MHz, Chloroform-d) δ 7.98 (s, 1H), 7.59 (dd, J = 8.2, 1.8 Hz, 1H), 7.48 (d, J = 8.2 Hz, 1H), 2.46 (s, 3H), 1.39 (s, 9H). 13C NMR (125 MHz, Chloroform-d) δ 167.5, 160.4, 144.4, 138.3, 137.5, 127.8, 126.7, 116.5, 37.8, 27.7, 21.2. HRMS (ESI) m / z: [M+H]+ Calcd. for C13H16NO2: 218.1176, found 218.1169.

[0037] Example 3:

[0038] A preparation method of a 4H-benzo[d][1,3]oxazin-4-one compound of the present invention includes: successively adding aniline (0.1 mmol), [Cp * Rh(MeCN)3][SbF6]2 (10 mol%), silver acetate (0.3 mmol), and acetic anhydride (0.15 mmol) into a dry 10 mL reaction tube, adding 1 mL of dichloroethane solution, purging and replacing with a carbon monoxide balloon three times, stirring and reacting at 95 °C in an oil bath for 24 h. After the reaction is completed, add Et3N (0.1 mmol, 13.5 μL), and purify by silica gel column chromatography (eluent: PE / EA = 3:1 (v / v)) to obtain the white solid 2-methyl-4H-benzo[d][1,3]oxazin-4-one (11.1 mg, 69% yield).

[0039] The structure of the product is as follows:

[0040]

[0041] The structure characterization is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 8.19 (dd, J = 7.9, 1.3 Hz, 1H), 7.82 - 7.76 (m, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 2.47 (s, 3H). 13 C NMR (125 MHz, Chloroform-d) δ 160.2, 159.7, 146.4, 136.5, 128.4, 128.2, 126.4, 116.6, 21.4. HRMS (ESI) m / z: [M+H] + Calcd. for C9H8NO2, 162.0550, found 162.0548.

[0042] Example 4:

[0043] A preparation method of a 4H-benzo[d][1,3]oxazin-4-one compound of the present invention includes:

[0044] To a dry 10 mL reaction tube, N-trimethylacetylaniline (0.1 mmol), [RhCp*Cl2] (5 mol%), silver pivalate (0.3 mmol), acetic anhydride (0.15 mmol), and AgNTf2 (0.02 mmol) were successively added. 1 mL of dichloroethane solution was added, and the mixture was evacuated and backfilled with carbon monoxide three times. The reaction was stirred at 95 °C in an oil bath for 24 h. After the reaction was completed, purification was carried out by silica gel column chromatography (eluent: PE / EA = 20:1 (v / v)), and the white solid 2-(tert-butyl)-4H-benzo[d][1,3]oxazin-4-one (11.4 mg, 56% yield) was obtained.

[0045] The structure of the product is as follows:

[0046]

[0047] The structure characterization data are as follows: 1 H NMR (500 MHz, Chloroform-d) δ 8.19 (d, J = 7.9 Hz, 1H), 7.78 (t, J = 7.7 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 1.40 (d, J = 0.6 Hz, 9H). 13 C NMR (125 MHz, Chloroform-d) δ 168.2, 160.1, 146.5, 136.2, 128.2, 128.0, 126.9, 116.8, 37.9, 27.7. HRMS (ESI) m / z:

[0048] [M+H]+ Calcd. for C 12 H 14 NO2 204.1019 found 204.1016.

[0049] Example 5:

[0050] A method for preparing a 4H-benzo[d][1,3]oxazin-4-one compound of the present invention includes:

[0051] To a dry 10 mL reaction tube, N-trimethylacetyl-2-naphthylamine (0.1 mmol), [Cp *[Rh(MeCN)3][SbF6]2 (10 mol %), silver acetate (0.3 mmol), acetic anhydride (0.05 mmol) were added to 1 mL of dichloroethane solution. The mixture was evacuated and backfilled with carbon monoxide balloon three times, and then stirred at 105 °C in an oil bath for 24 h. After the reaction, it was purified by silica gel column chromatography (eluent: PE / EA = 10:1 (v / v)) to obtain the white solid 2-(tert-butyl)-4H-naphtho[2,3-d][1,3]oxazin-4-one (18.2 mg, 72% yield). The structure of the product is as follows:

[0052]

[0053] The structure characterization data are as follows: 1 1H NMR (500 MHz, Chloroform-d) δ 8.82 (s, 1H), 8.05 (s, 1H), 8.02 (d, J = 8.3 Hz, 1H), 7.95 (d, J = 8.3 Hz, 1H), 7.66 (d, J = 7.0 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 1.44 (s, 9H). 13 13C NMR (125 MHz, Chloroform-d) δ

[0054] 166.3, 160.5, 141.0, 137.5, 132.1, 130.7, 129.5, 129.5, 128.1, 126.9, 124.8, 115.5, 37.9, 27.7. HRMS (ESI) m / z: [M + H] + Calcd. for C 16 H 15 NO2, 254.1176 found 254.1173.

[0055]

[0056] As described above, it is only the preferred embodiment of the present invention, and it does not impose any form of limitation on the present invention. Any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A preparation method of 4H-benzo[d][1,3]oxazin-4-one compounds, comprising the following steps: (1) Mix anilide compounds or aniline compounds, a rhodium catalyst, an oxidant, and an additive in a molar ratio of 1:(0.001 - 0.1):(0.1 - 5):(0 - 2) with dichloroethane, such that the molar concentration of the anilide compounds or aniline compounds is 0.05 - 0.5 M, and react at 50 - 120 °C for 12 - 30 h under a carbon monoxide gas atmosphere; (2) Separate and purify to obtain 4H-benzo[d][1,3]oxazin-4-one compounds, and their structural formula is as follows: The rhodium catalyst is [RhCp*(MeCN)3][SbF6]2; The oxidant is silver acetate, silver pivalate; The additive is AgNTf2, acetic anhydride.

2. The preparation method of a 4H-benzo[d][1,3]oxazin-4-one compound according to claim 1, wherein: The molar ratio of anilide compounds or aniline compounds, a rhodium catalyst, an oxidant, and an additive is 1:0.1:3:1.

5.

3. The preparation method of a 4H-benzo[d][1,3]oxazin-4-one compound as claimed in claim 1, wherein: The molar concentration of the anilide compounds or aniline compounds is 0.1 M.

4. The preparation method of a 4H-benzo[d][1,3]oxazin-4-one compound as claimed in claim 1, wherein: The reaction temperature is 90 - 100 °C.

5. A method for preparing a 4H-benzo[d][1,3]oxazin-4-one compound according to any one of claims 1-4, wherein: The oxidant is silver acetate.

6. The preparation method of a 4H-benzo[d][1,3]oxazin-4-one compound according to any one of claims 1-4, wherein: The additive is acetic anhydride.

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