Preparation method of 1-fluoro-2-nitronaphthalene

Abstract

The invention relates to the technical field of medicine synthesis, and particularly discloses a preparation method of 1-fluoro-2-nitronaphthalene. According to the preparation method of the 1-fluoro-2-nitronaphthalene, provided by the invention, the 1-fluoro-2-nitronaphthalene is prepared by taking 1-fluoro-2-naphthylboronic acid as a raw material and carrying out in-situ nitration reaction in the presence of a nitration reagent; the nitration reagent is one or two of ferric nitrate and bismuth nitrate. According to the preparation method of the 1-fluoro-2-nitronaphthalene provided by the invention, a catalyst and alkali do not need to be used during preparation, only a nitration reagent is used, the 1-fluoro-2-naphthyl boric acid is used as a raw material, and the 1-fluoro-2-nitronaphthalene can be prepared at a high yield by in-situ nitration at a relatively low temperature and normal pressure; the method is mild in reaction condition, low in cost, simple to operate, green, environment-friendly, safe, efficient, extremely high in practical value and beneficial to industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical synthesis, and particularly to a method for preparing 1-fluoro-2-nitronaphthalene. Background Art

[0002] Aromatic nitro compounds are a very important class of organic compounds and have extensive applications in the fields of medicine, pesticides, dyes, spices, explosives, etc. However, the nitration reaction involving concentrated nitric acid and concentrated sulfuric acid commonly used in the preparation of aromatic nitro compounds is listed as a class of hazardous chemical reactions.

[0003] Currently, there are very few reports on the synthesis methods of aromatic compounds such as 1-fluoro-2-nitronaphthalene, and their preparation yields are extremely low and the selectivity is poor. For example, it is reported in J.Chem.Soc.(C), 1966 that by diazotizing the corresponding nitro naphthylamine fluoroborate in a tetrahydrofuran solvent and then decomposing the diazonium fluoroborate, 1-fluoro-2-nitronaphthalene can be prepared with a yield of 10 - 15%, and the reaction formula is as follows:

[0004]

[0005] This method has the problem of extremely low yield and is not conducive to large-scale production.

[0006] Based on the above situation, how to provide a method for preparing 1-fluoro-2-nitronaphthalene with mild reaction conditions, simple operation, green environmental protection, safety and high efficiency, high yield and high purity to solve the problem of low yield in the above process has become an urgent technical problem to be solved.

[0007] Therefore, the present invention aims to develop a new method for preparing 1-fluoro-2-nitronaphthalene. Summary of the Invention

[0008] The main technical problem to be solved by the present invention is to provide a method for preparing 1-fluoro-2-nitronaphthalene.

[0009] To solve the above technical problem, the technical solution adopted by the present invention is: a method for preparing 1-fluoro-2-nitronaphthalene, which uses 1-fluoro-2-naphthylboronic acid as a raw material and prepares 1-fluoro-2-nitronaphthalene through an in-situ nitration reaction in the presence of a nitrating reagent; the nitrating reagent is one or two of iron nitrate and bismuth nitrate.

[0010] The method for preparing 1-fluoro-2-nitronaphthalene provided by the present invention involves the following reaction formula:

[0011]

[0012] As an embodiment of the present invention, the molar ratio of the 1-fluoro-2-naphthylboronic acid to the nitrating reagent is 1:(1-2).

[0013] As an embodiment of the present invention, the in-situ nitration reaction is carried out in toluene and / or 1,4-dioxane solvent.

[0014] As an embodiment of the present invention, the reaction temperature of the in-situ nitration reaction is 60-85 °C.

[0015] As an embodiment of the present invention, the reaction time of the in-situ nitration reaction is 12-18 h.

[0016] As a preferred embodiment of the present invention, the reaction temperature of the in-situ nitration reaction is 80-85 °C.

[0017] As a preferred embodiment of the present invention, the reaction time of the in-situ nitration reaction is 12-15 h.

[0018] As an embodiment of the present invention, the in-situ nitration reaction is carried out under normal pressure.

[0019] Preferably, the molar ratio of the 1-fluoro-2-naphthylboronic acid to the nitrating reagent is 1:(1.4-1.6). Specifically, the molar ratio of the 1-fluoro-2-naphthylboronic acid to the nitrating reagent can be 1:1.4, 1:1.45, 1:1.5, 1:1.55, 1:1.6 or any other value within the range of 1:(1.4-1.6).

[0020] Preferably, the in-situ nitration reaction is carried out in toluene solvent.

[0021] The preparation method of 1-fluoro-2-nitronaphthalene provided by the present invention does not require the use of a catalyst and a base during preparation, only uses a nitrating reagent, and uses 1-fluoro-2-naphthylboronic acid as a raw material to carry out in-situ nitration at a lower temperature and normal pressure, and 1-fluoro-2-nitronaphthalene can be prepared in a high yield. This method has mild reaction conditions, low cost, simple operation, environmental friendliness, safety and high efficiency, has extremely high practical value, and is conducive to industrial production.

[0022] In the preparation method of 1-fluoro-2-nitronaphthalene provided by the present invention, after the reaction is completed, the reactants are filtered, extracted, and then subjected to column chromatography to obtain a high-purity 1-fluoro-2-nitronaphthalene product. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 is the 1 1H-NMR spectrum of 1-fluoro-2-nitronaphthalene prepared in Example 1 of the present invention;

[0024] Figure 2It is the GC chromatogram of 1-fluoro-2-nitronaphthalene prepared in Example 1 of the present invention;

[0025] Figure 3 It is the GC-MS chromatogram of 1-fluoro-2-nitronaphthalene prepared in Example 1 of the present invention. Detailed implementation manners

[0026] The technical solution of the present invention will be described in detail below through specific examples. The following examples are intended to further illustrate the content of the present invention in detail, rather than limiting the scope of protection of the claims of the present invention.

[0027] In the following examples, unless otherwise specified, the reagents used are all commercially available products.

[0028] Example 1

[0029] This example provides a preparation method of 1-fluoro-2-nitronaphthalene, and the reaction formula is:

[0030]

[0031] Take a 1L three-necked flask as the reaction vessel, add 50 g of 1-fluoro-2-naphthylboronic acid (263 mmol) to 500 mL of toluene, and then add 159 g of iron(III) nitrate nonahydrate (394 mmol). The temperature of the system is raised to 85 °C, and the reaction is stirred for 14 h under atmospheric pressure. The reaction is detected to be complete by TLC.

[0032] Cool the system to 20 °C, and filter to remove insoluble substances. Then concentrate to remove the solvent, and purify by column chromatography (the eluent is PE:EA = 80:1) to obtain 25.7 g (134 mmol) of yellow solid, that is, 1-fluoro-2-nitronaphthalene, with a yield of 51%.

[0033] Example 2

[0034] This example provides a preparation method of 1-fluoro-2-nitronaphthalene, and the reaction formula is the same as that shown in Example 1. Take a 1L three-necked flask as the reaction vessel, add 50 g of 1-fluoro-2-naphthylboronic acid (263 mmol) to 500 mL of toluene, and then add 106 g of iron(III) nitrate nonahydrate (263 mmol). The temperature of the system is raised to 85 °C, and the reaction is stirred for 14 h under atmospheric pressure. The reaction is detected to be complete by TLC.

[0035] Cool the system to 17 °C, and filter to remove insoluble substances. Then concentrate to remove the solvent, and purify by column chromatography (the eluent is PE:EA = 80:1) to obtain 22.6 g (118 mmol) of yellow solid, that is, 1-fluoro-2-nitronaphthalene, with a yield of 45%.

[0036] Example 3

[0037] This example provides a method for preparing 1-fluoro-2-nitronaphthalene. The reaction formula is the same as that shown in Example 1. Take a 1 L three-necked flask as the reaction vessel, add 50 g of 1-fluoro-2-naphthylboronic acid (263 mmol) to 500 mL of toluene, and then add 213 g of iron(III) nitrate nonahydrate (526 mmol). Heat the system to 85 °C and stir the reaction under atmospheric pressure for 14 h. TLC detection shows that the reaction is complete.

[0038] Cool the system to 18 °C and filter off the insoluble matter. Then concentrate to remove the solvent and purify by column chromatography (eluent: PE:EA = 80:1) to obtain 19.1 g (100 mmol) of a yellow solid, which is 1-fluoro-2-nitronaphthalene, with a yield of 38%.

[0039] Example 4

[0040] This example provides a method for preparing 1-fluoro-2-nitronaphthalene. The reaction formula is the same as that shown in Example 1. Take a 1 L three-necked flask as the reaction vessel, add 50 g of 1-fluoro-2-naphthylboronic acid (263 mmol) to 500 mL of toluene, and then add 156 g of bismuth nitrate (395 mmol). Heat the system to 85 °C and stir the reaction under atmospheric pressure for 14 h. TLC detection shows that the reaction is complete.

[0041] Cool the system to 15 °C and filter off the insoluble matter. Then concentrate to remove the solvent and purify by column chromatography (eluent: PE:EA = 80:1) to obtain 20.6 g (108 mmol) of a yellow solid, which is 1-fluoro-2-nitronaphthalene, with a yield of 41%.

[0042] Example 5

[0043] This example provides a method for preparing 1-fluoro-2-nitronaphthalene. The reaction formula is the same as that shown in Example 1. Take a 1 L three-necked flask as the reaction vessel, add 50 g of 1-fluoro-2-naphthylboronic acid (263 mmol) to 500 mL of 1,4-dioxane, and then add 159 g of iron(III) nitrate nonahydrate (394 mmol). Heat the system to 85 °C and stir the reaction under atmospheric pressure for 14 h. TLC detection shows that there is remaining reaction raw material. Continue to stir the reaction for 3 h with no change, and then end the reaction.

[0044] Cool the system to 18 °C and filter off the insoluble matter. Then concentrate to remove the solvent and purify by column chromatography (eluent: PE:EA = 80:1) to obtain 17.6 g (92 mmol) of a yellow solid, which is 1-fluoro-2-nitronaphthalene, with a yield of 35%.

[0045] The 1-fluoro-2-nitronaphthalene prepared in Example 1 was subjected to nuclear magnetic resonance analysis, and the resulting nuclear magnetic resonance1 The H-NMR spectrum is as follows Figure 1 shown. The GC spectrum of 1-fluoro-2-nitronaphthalene is shown in Figure 2 , and the GC-MS spectrum is shown in Figure 3 . From Figure 1 , Figure 2 and Figure 3 , it can be seen that the target product 1-fluoro-2-nitronaphthalene was successfully prepared, and the purity was greater than 99%.

[0046] As can be seen from the above examples, when the molar ratio of the feed of 1-fluoro-2-naphthylboronic acid to the nitrating reagent is about 1:1.5, the product yield is relatively high. The nitration reaction is preferably carried out in toluene.

[0047] The above are only the embodiments of the present invention, and do not limit the patent scope of the present invention accordingly. Any equivalent transformation made by using the content of the specification of the present invention, directly or indirectly applied in other related technical fields, is included in the patent protection scope of the present invention.

Claims

1. A method for preparing 1-fluoro-2-nitronaphthalene, characterized in that, Using 1-fluoro-2-naphthylboronic acid as a raw material, in the presence of a nitrating reagent, 1-fluoro-2-nitronaphthalene is prepared through an in-situ nitration reaction; the nitrating reagent is one or two of iron nitrate and bismuth nitrate.

2. The preparation method according to claim 1, wherein The molar ratio of the feed of the 1-fluoro-2-naphthylboronic acid to the nitrating reagent is 1:(1-2).

3. The preparation method according to claim 1, wherein The in-situ nitration reaction is carried out in a toluene and / or 1,4-dioxane solvent.

4. The preparation method according to claim 1, wherein, The reaction temperature of the in-situ nitration reaction is 60-85 °C.

5. The preparation method according to claim 4, characterized in that, The reaction time of the in-situ nitration reaction is 12-18 h.

6. The preparation method according to claim 4, characterized in that, The reaction temperature of the in-situ nitration reaction is 80-85 °C.

7. The preparation method according to claim 6, characterized in that, The reaction time of the in-situ nitration reaction is 12-15 h.

8. The preparation method according to claim 1, characterized in that, The in-situ nitration reaction is carried out under atmospheric pressure.

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