O-dinitrate compound as well as preparation method and application thereof

Abstract

The invention discloses an o-dinitrate compound as well as a preparation method and application thereof, the general formula is as follows: # imgabs0 #, and R, R1, R2 and R3 are alkyl, aryl or hydrogen. According to the compound, simple olefin is used as a starting material, an acyclic high-iodine nitrate reagent is used as a nitrate source, and the ortho-dinitrate compound is prepared in one step under the conditions of a specific solvent and a specific temperature. Compared with the prior art, the method has the advantages that the high-valence iodine ortho-dinitrate compound is generated in situ, simple olefin raw materials are utilized, and the ortho-dinitrate compound which is efficient, green, safe and capable of being prepared in a large scale is developed through one-step bifunctionalization.

Description

Technical Field

[0001] The invention belongs to the field of organic synthetic chemistry and relates to an in-situ generated high-valent iodine o-dinitrate compound and a preparation method and application thereof. Background Art

[0002] Over the past century, nitric oxide, as a key signaling molecule, has played a variety of biological roles in a variety of physiological and pathological processes, such as vasodilation, platelet aggregation, neurotransmission and immune regulation. Nitrate compounds are one of the most effective donors of nitric oxide (NO) and are often used as drugs and bioactive molecules. For example, nitroglycerin (GTN), isoprenaline (ISMN), changxinda (ISDN), Nipradilol, Nicorandil, etc. are all commonly used and effective emergency drugs for cardiovascular diseases. The key to the synthesis of organic nitrate compounds is the selection of nitrate groups. With the continuous development of many chemists, the nitrate source has evolved from the more toxic ammonium cerium nitrate (Tetrahedron Letters 2011, 52, 4654-4657), cheap metal nitrates (ACS Catalysis 2021, 11, 14188-14193), tert-butyl nitrite (TBN) and oxygen (Advanced Synthesis & Catalysis 2016, 358, 1942-1945), and periodic nitrate (Angewandte Chemie International Edition 2020, 59, 17162-17168). However, there are still limitations such as limited substrates, high pollution toxicity, and harsh experimental conditions.

[0003] Olefin difunctionalization refers to the introduction of two functional groups into the carbon-carbon double bond of an olefin. In this reaction, the functional group is nitrate (NO 3 ) and form an ortho-dinitrate unit (i.e. two nitrate groups attached to adjacent carbon atoms). This type of reaction is very valuable in synthetic chemistry because it allows the creation of highly functionalized compounds in molecules that can be used to develop explosives, plasticizers or other specialty materials. It is worth noting that in 1988, the Sebastiani group and the Baciocchi group reported the dinitration of olefins using ammonium cerium nitrate under ultraviolet light (Tetrahedron 1988, 44, 6651-6660), but the substrate range was small and the use of ammonium cerium nitrate as a nitrate source was highly toxic.

[0004] Professor Deng Qinghai's team at Shanghai Normal University has developed a non-cyclic periodinitiator nitrate transfer reagent (Chinese patent applications CN 114436846 A and CN 116178162 A). This type of reagent has been successfully applied to direct nitration reactions using non-metallic nitrates as nitrate sources, including: (1) safe and efficient direct nitration of compounds such as β-ketoesters / amides, 1,3-diketones, and β-naphthol; (2) ring-opening nitration of cyclopropylsilyl ethers to obtain a series of β-nitrate ester ketone compounds (Angew. Chem. Int. Ed. 2023, 62, e202302521).

[0005] The types of the above-mentioned disclosed organic nitrates are limited, and there are problems such as narrow application range of the synthesis method substrate, low safety, poor selectivity, and the use of more metal nitrates. In particular, how to achieve the synthesis of olefin dinitrates without using mixed acids or metal nitrates is a great challenge. The present invention provides an ortho-dinitrate compound and a preparation method thereof. Summary of the invention

[0006] The purpose of the present invention is to overcome the defects of the above-mentioned prior art and provide a method for in-situ generation of a high-valent iodine o-dinitrate compound and a preparation method and application thereof, aiming to utilize simple olefin raw materials and develop an efficient, green, safe and large-scale preparable o-dinitrate compound through a one-step double functionalization.

[0007] The purpose of the present invention can be achieved by the following technical scheme: an o-dinitrate compound, the general formula of which is as follows:

[0008]

[0009] Among them, R, R 1 , R 2 , R 3 is alkyl, aryl or hydrogen.

[0010] Furthermore, R is an alkyl group (1-decyl, benzyl, 1-phenylethyl, 1-(CH 2 ) n -Br, 1-(CH 2 ) n -OOCAr, etc.), aryl (phenyl, 4-chloromethylphenyl, 4-tert-butylphenyl, 4-acetoxyphenyl, 4-methoxycarbonylphenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 4-nitrophenyl, 4-fluorophenyl, 4-iodophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, etc.) or hydrogen; R 1 and R 2 is an alkyl group (methyl, etc.) or hydrogen; R 3 It is an alkyl group (methyl group, etc.), an aryl group (phenyl group) or hydrogen.

[0011] The present invention also provides a method for preparing o-dinitrate compounds, wherein an in-situ generated non-cyclic periodinitrate reagent is used as a nitrate source in an organic solvent, and olefins are directly added to the reaction system for reaction to generate o-dinitrate compounds.

[0012] Furthermore, the method is specifically as follows: at 25 to 35° C., in an air atmosphere, firstly, diacetyl iodobenzene and nitric acid are added to a solvent solution, stirred for 20 to 60 minutes to obtain a non-cyclic periodinitrate reagent, then olefin is added, and the reaction is continued for 5 to 8 hours. Finally, the reaction solution is concentrated and subjected to column chromatography to obtain a pure o-dinitrate product.

[0013] The reaction formula is as follows:

[0014]

[0015] Furthermore, the molar ratio of diacetyl iodobenzene to nitric acid is 1:2-1:3.

[0016] Furthermore, the volume concentration of the nitric acid is 60-70%.

[0017] Furthermore, the solvent is dichloromethane, 1,2-dichloroethane, toluene or chloroform.

[0018] Furthermore, the amount of the solvent used is 10 liters of solvent per mole of diacetyl iodobenzene.

[0019] Furthermore, the molar ratio of the olefin to the acyclic periodinitrate reagent is 1:(1.2-1.8).

[0020] The molar ratio of the olefin to diacetoxy iodobenzene and nitric acid is 1:1.5:3-1:2:4;

[0021] The present invention also provides an application of an o-dinitrate compound, wherein the o-dinitrate compound is used to convert a nitrate group to other functional groups, such as a hydroxyl group or an azide group.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] (1) The o-dinitrate compound provided by the present invention has a C2 symmetrical structure, good stability and high reactivity. It not only has great potential for drug development, but also is an excellent leaving group, capable of converting between functional groups under corresponding reaction conditions, such as hydroxyl and azide groups. It has a high prospect for synthetic application.

[0024] (2) The o-dinitrate compounds of the present invention use simple olefins as starting materials, generate high-valent iodine o-dinitrate compounds in situ, directly add olefins to the reaction system for reaction, and generate o-dinitrate compounds, thereby realizing the dinitration synthesis of olefins without using mixed acid or metal nitrates. Compared with the previous dinitration reaction, which requires the use of cerium ammonium nitrate and harsh conditions of light, and the substrate range is relatively limited. The substrate of the present invention has a wide range of application, high safety, high selectivity, and no need to use metal nitrates. The olefins used in the present invention are cheap and easy to obtain, and are widely present in natural products and drug molecules. The ability to directly realize the dinitration reaction of olefins has already reflected its research significance in organic synthesis and medicinal chemistry.

[0025] (3) The present invention utilizes the characteristics of the dinitrate group of the product to further derivatize the product to generate compounds with other important groups. At the same time, a method for introducing an ortho-dinitrate group into an existing drug molecule is disclosed, which has broad potential application value in scientific research such as organic synthesis and drug development.

[0026] (4) Compared with other methods, the method of the present invention has the following advantages:

[0027] The operation is simple: there is no need to separate and purify the high-valent iodine nitrate reagent, and it can be directly generated in situ in the system. By double functionalization with the added olefin, the o-dinitrate compound is obtained, thus avoiding the waste of raw materials and solvents.

[0028] Green and safe: Avoiding the use of cerium ammonium nitrate or mixed acid system of nitric acid and sulfuric acid, it has also made great improvements in environmental protection. At the same time, compared with other methods, the present invention avoids the use of finished periodic nitrate reagents, and has also significantly improved the safety of large-scale synthesis. DETAILED DESCRIPTION

[0029] The following is a detailed description of an embodiment of the present invention. This embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation method and a specific operation process are given, but the protection scope of the present invention is not limited to the following embodiment.

[0030] The olefins, diacetoxyiodobenzene (PhI(OAc)) used in the following examples are 2 ), nitric acid, and dichloromethane were purchased from commercial sources.

[0031] Example 1

[0032] The preparation of 1,2-octyl dinitrate is carried out according to the following reaction equation:

[0033]

[0034] The specific steps are:

[0035] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% aqueous nitric acid solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 1-octene (22.42 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 36 mg, 76% yield) was obtained after spin drying.

[0036] The characterization data are as follows:

[0037] 1 H NMR (400 MHz, CDCl 3 )δ5.28(qd,J=6.8,2.8Hz,1H),4.74(dd,J=12.8,3.2Hz,1H),4.46(dd,J=12.8,6.8H z,1H),1.83-1.63(m,2H),1.52-1.38(m,2H),1.38-1.26(m,6H),0.94-0.83(m,3H). 13 C NMR (101 MHz, CDCl 3 )δ79.4,71.4,31.5,29.4,28.9,25.0,22.6,14.1.

[0038] Example 2

[0039] The preparation of 1,2-decyl dinitrate is carried out according to the following reaction equation:

[0040]

[0041] The specific steps are:

[0042] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 1-decene (28.05 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 38 mg, 72% yield) was obtained after spin drying.

[0043] The characterization data are as follows:

[0044] 1 H NMR (400 MHz, CDCl 3 )δ5.28(qd,J=6.8,2.8Hz,1H),4.74(dd,J=12.8,2.8Hz,1H),4.46(dd,J=12.8,6.8Hz, 1H),1.82-1.63(m,2H),1.52-1.38(m,2H),1.37-1.18(m,10H),0.88(t,J=6.8Hz,3H); 13 C NMR (101 MHz, CDCl 3 )δ79.4,71.4,31.9,29.4,29.3,29.3,29.2,25.0,22.7,14.2.

[0045] Example 3

[0046] The preparation of 1,2-undecyl dinitrate is carried out according to the following reaction equation:

[0047]

[0048] The specific steps are:

[0049] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% aqueous nitric acid solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 1-undecene (30.86 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 41 mg, 74% yield) was obtained after spin drying.

[0050] The characterization data are as follows:

[0051] 1 H NMR (400 MHz, CDCl 3 )δ5.28(qd,J=6.8,2.8Hz,1H),4.74(dd,J=12.8,2.8Hz,1H),4.46(dd,J=12.8,6.8Hz, 1H),1.84-1.63(m,2H),1.52-1.38(m,2H),1.35-1.21(m,12H),0.88(t,J=6.6Hz,3H); 13 C NMR (101 MHz, CDCl 3)δ79.4,71.4,31.9,29.5,29.4,29.4,29.3,29.3,25.0,22.8,14.2.

[0052] Example 4

[0053] The preparation of 1,2-dinitrate is carried out according to the following reaction equation:

[0054]

[0055] The specific steps are:

[0056] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% aqueous nitric acid solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 1-dodecene (33.66 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 51 mg, 88% yield) was obtained after spin drying.

[0057] The characterization data are as follows:

[0058] 1 H NMR (400 MHz, CDCl 3 )δ5.36-5.22(m,1H),4.74(dd,J=12.8,2.8Hz,1H),4.46(dd,J=12.8,6.8Hz,1 H),1.77-1.69(m,2H),1.49-1.39(m,2H),1.26(s,14H),0.88(t,J=6.7Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ79.4,71.4,32.0,29.6,29.5,29.4,29.4,29.3,29.2,25.0,22.8,14.2.

[0059] Example 5

[0060] The preparation of 1,2-tridecyl dinitrate is carried out according to the following reaction equation:

[0061]

[0062] The specific steps are:

[0063] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 1-tridecene (36.47 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 47 mg, 77% yield) was obtained after spin drying.

[0064] The characterization data are as follows:

[0065] 1 H NMR (400 MHz, CDCl 3 )δ5.28(qd,J=6.8,2.8 Hz,1H),4.74(dd,J=12.8,2.Hz,1H),4.46(dd,J=12.8,6.8 Hz,1H),1.79-1.66(m,2H),1.48-1.35(m,3H),1.26(s,16H),0.88(t,J=6.7 Hz,3H). 13 C NMR (101 MHz, CDCl 3 )δ79.4,71.4,32.0,29.7,29.7,29.5,29.46,29.44,29.39,29.27,25.0,22.8,14.2.

[0066] Example 6

[0067] The preparation of 1-benzyl-1,2-ethyl dinitrate is carried out according to the following reaction equation:

[0068]

[0069] The specific steps are:

[0070] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, allylbenzene (23.64 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 26.4 mg, 55% yield) was obtained after spin drying.

[0071] The characterization data are as follows:

[0072] 1 H NMR (400 MHz, CDCl 3 )δ7.39-7.28(m,3H),7.28-7.21(m,2H),5.47(qd,J=6.8,2.8 Hz,1H),4.76-4.70(m,1H),4.43(dd,J=12.8,6.4 Hz,1H),3.12(dd,J=14.0,6.8 Hz,1H),3.01(dd,J=14.4,7.2 Hz,1H); 13 C NMR (101 MHz, CDCl 3 )δ134.2,129.3,129.2,127.8,79.6,70.2,35.7.

[0073] Example 7

[0074] The preparation of 1-benzyl methyl ether-1,2-ethyl dinitrate is carried out according to the following reaction equation:

[0075]

[0076] The specific steps are:

[0077] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, allyl benzyl ether (29.64 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 30.7 mg, 57% yield) was obtained after spin drying.

[0078] The characterization data are as follows:

[0079] 1 H NMR (400 MHz, CDCl 3 )δ7.39-7.28(m,3H),7.28-7.21(m,2H),5.47(qd,J=6.8,2.8Hz,1H),4.76-4.70(m,1H), 4.43(dd,J=12.8,6.4Hz,1H), 3.12(dd,J=14.0,6.8Hz,1H), 3.01(dd,J=14.4,7.2Hz,1H); 13 C NMR (101 MHz, CDCl 3)δ134.2,129.3,129.2,127.8,79.6,70.2,35.7.

[0080] Example 8

[0081] The preparation of 11-chloro-1,2-dinitrate undecyl ester is carried out according to the following reaction equation:

[0082]

[0083] The specific steps are:

[0084] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 11-chloro-1-undecene (37.75 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 55 mg, 88% yield) was obtained after spin drying.

[0085] The characterization data are as follows:

[0086] 1 H NMR (400 MHz, CDCl 3 )δ5.28(ddt,J=9.6,6.8,3.6Hz,1H),4.74(dd,J=12.8,2.8Hz,1H),4.46(dd,J=12.8,6.8 Hz,1H),3.52(t,J=6.8Hz,2H),1.81-1.66(m,4H),1.51-1.36(m,5H),1.37-1.23(m,9H). 13 C NMR (101 MHz, CDCl 3 )δ79.4,71.4,45.3,32.7,29.4,29.3,29.2,29.1,28.9,26.9,25.0.

[0087] Example 9

[0088] The preparation of 8-bromo-1,2-octyl dinitrate is carried out according to the following reaction equation:

[0089]

[0090] The specific steps are:

[0091] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% aqueous nitric acid solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 8-bromo-1-octene (38.22 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 50 mg, 80% yield) was obtained after spin drying.

[0092] The characterization data are as follows:

[0093] 1 H NMR (400MHz, CDCl3) δ5.28 (ddt, J=9.2, 6.8, 3.2Hz, 1H), 4.74 (dd, J=12.8, 3.2Hz, 1H), 4.47 (dd, J=12.8, 6.8 Hz,1H),3.41(t,J=6.8Hz,2H),1.92-1.80(m,2H),1.80-1.68(m,2H),1.55-1.41(m,4H),1.43-1.33(m,2H). 13 C NMR (101MHz, CDCl3) δ79.2,71.3,33.7,32.5,29.3,28.4,27.9,24.9.

[0094] Example 10

[0095] The preparation of 9,10-decyl dinitrate of acetic acid is carried out according to the following reaction equation:

[0096]

[0097] The specific steps are:

[0098] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 9-decenyl acetate (39.66 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 52 mg, 81% yield) was obtained after spin drying.

[0099] The characterization data are as follows:

[0100] 1H NMR (400 MHz, CDCl 3 )δ5.27(qd,J=6.8,2.8Hz,1H),4.73(dd,J=12.8,2.8Hz,1H),4.46(dd,J=12.8,6.8Hz,1H),4.04(t ,J=6.8Hz,2H),2.04(s,3H),1.79-1.66(m,2H),1.65-1.55(m,3H),1.51-1.37(m,2H),1.31(s,9H). 13 C NMR (101 MHz, CDCl 3 )δ171.4,79.3,71.4,64.6,29.4,29.2,29.1,29.1,28.6,25.9,25.0,21.1.

[0101] Embodiment 11

[0102] The preparation of 4,5-pentyl dinitrate of fluorobenzoic acid is carried out according to the following reaction equation:

[0103]

[0104] The specific steps are:

[0105] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 4-pentenyl-4-fluorobenzoate (41.65 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 10:1. The pure product was obtained after drying (colorless to light yellow liquid, 42 mg, 64% yield).

[0106] The characterization data are as follows:

[0107] 1 H NMR (400 MHz, CDCl 3 )δ8.04(dd,J=8.8,5.6Hz,2H),7.12(t,J=8.8Hz,2H),5.50-5.29(m,1H),4.77(dd,J=12 .8,3.2Hz,1H),4.50(dd,J=12.8,6.4Hz,1H),4.36(q,J=5.2Hz,2H),2.07-1.82(m,4H). 13 C NMR (101 MHz, CDCl 3)δ165.6(t,J=89.8Hz),132.3(d,J=10.1Hz),126.17(d,J=3.1Hz),115.7(d,J=22.2Hz),78.6,71.2,63.9,26.3,24.5. 19 FNMR (376MHz, CDCl 3 )δ-105.2.

[0108] Example 12

[0109] The preparation of 4-trifluorobenzoic acid-7,8-dinitrate octyl ester is carried out according to the following reaction equation:

[0110]

[0111] The specific steps are:

[0112] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 7-octenyl trifluorobenzoate (60.47 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 4:1. The pure product (colorless to light yellow liquid, 62 mg, 74% yield) was obtained after spin drying.

[0113] The characterization data are as follows:

[0114] 1 H NMR (400 MHz, CDCl 3 )δ8.14(d,J=8.0Hz,2H),7.70(d,J=8.0Hz,2H),5.28(qd,J=6.8,2.8Hz,1H),4.74(dd,J=12.8,3.2 Hz,1H),4.46(dd,J=12.8,6.8Hz,1H),4.35(t,J=6.8Hz,2H),1.85-1.68(m,4H),1.55-1.35(m,6H). 13 C NMR (101 MHz, CDCl 3 )δ165.5,134.4(q,J=32.3Hz),130.6,125.5(q,J=4.04Hz),123.7(q,J=273.7Hz),79.2,71.3,65.4,29.3,28.9,28.6,25.8,24.9. 19 F NMR (376 MHz, CDCl3 )δ-63.1

[0115] Example 13

[0116] The preparation of 4-acetylbenzoic acid-7,8-dinitrate octyl ester is carried out according to the following reaction equation:

[0117]

[0118] The specific steps are:

[0119] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 7-octenyl-4-acetylbenzoate (54.87 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 4:1. The pure product was obtained after drying (colorless to light yellow liquid, 47 mg, 59% yield).

[0120] The characterization data are as follows:

[0121] 1 H NMR (400 MHz, CDCl 3 )δ8.10(d,J=8.4Hz,2H),8.00(d,J=8.4Hz,2H),5.34-5.20(m,1H),4.73(dd,J=12.8,3.2Hz,1H),4.4 6(dd,J=12.8,6.8Hz,1H),4.34(t,J=6.4Hz,2H),2.63(s,3H),1.90-1.66(m,4H),1.54-1.38(m,6H); 13 CNMR (101MHz, CDCl 3 )δ197.6,165.8,140.3,134.2,129.9,128.3,79.2,71.3,65.3,29.3,28.9,28.6,26.9,25.8,24.9.

[0122] Embodiment 14

[0123] The preparation of octyl 4-methylsulfonylbenzoate-7,8-dinitrate is carried out according to the following reaction equation:

[0124]

[0125] The specific steps are:

[0126] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% aqueous nitric acid solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 7-octenyl-p-methylsulfonylbenzoate (62.08 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 4:1. The pure product (colorless to light yellow liquid, 84 mg, 99% yield) was obtained after spin drying.

[0127] The characterization data are as follows:

[0128] 1 H NMR (400 MHz, CDCl 3 )δ8.21(d,J=8.0Hz,2H),8.02(d,J=8.0Hz,2H),5.28(qd,J=6.4,2.8Hz,1H),4.73(dd,J=12.8,2.8Hz, 1H),4.46(dd,J=12.8,6.4Hz,1H),4.36(t,J=6.4Hz,2H),3.07(s,3H),1.86-1.68(m,4H),1.44(s,6H); 13 C NMR (101 MHz, CDCl 3 )δ165.1,144.3,135.2,130.6,127.6,79.2,71.3,65.7,44.4,29.3,28.8,28.5,25.8,24.9.

[0129] Embodiment 15

[0130] The preparation of 2-iodo-4-bromo-benzoic acid-7,8-dinitrate octyl ester is carried out according to the following reaction equation:

[0131]

[0132] The specific steps are:

[0133] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% aqueous nitric acid solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 2-iodo-4-bromo-benzoic acid-7-octenyl ester (87.42 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 4:1. The pure product (colorless to light yellow liquid, 60 mg, 54% yield) was obtained after spin drying.

[0134] The characterization data are as follows:

[0135] 1 H NMR (400 MHz, CDCl 3 )δ7.89(d,J=2.4Hz,1H),7.83(d,J=8.4Hz,1H),7.28(dd,J=8.4,2.4Hz,1H),5.39-5.22(m,1H),4.74(dd,J= 12.8,3.2Hz,1H),4.47(dd,J=12.8,6.8Hz,1H),4.33(t,J=6.6Hz,2H),1.89-1.65(m,4H),1.55-1.36(m,6H); 13 C NMR (101 MHz, CDCl 3 )δ165.4,142.7,137.0,135.7,133.8,122.3,92.1,79.2,71.3,66.0,29.3,28.9,28.4,25.8,24.9

[0136] Example 16

[0137] The preparation of 9-(diethoxyphosphoryl)butene-1,2-dinitrate is carried out according to the following reaction equation:

[0138]

[0139] The specific steps are:

[0140] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% aqueous nitric acid solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, 9-(diethoxyphosphoryl)butene (52.86 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 4:1. The pure product was obtained after drying (colorless to light yellow liquid, 58 mg, 78% yield).

[0141] The characterization data are as follows:

[0142] 1 H NMR (400 MHz, CDCl 3 )δ5.41-5.17(m,1H),4.75(dd,J=12.8,2.8Hz,1H),4.46(dd,J=12.8,6.4Hz,1H),4.17-3. 99(m,4H),1.78-1.65(m,4H),1.62-1.48(m,2H),1.47-1.32(m,6H),1.29(t,J=7.2Hz,6H); 13 C NMR (101 MHz, CDCl 3 )δ79.4,71.4,62.2,30.2,30.0,29.2,28.6,25.9,24.6,24.5,22.0,21.9,16.4,16.4; 31 P NMR (162 MHz, CDCl 3 )δ31.93.

[0143] Embodiment 17

[0144] The preparation of 1-(4-fluorophenyl)ethane-1,2-dinitrate is carried out according to the following reaction equation:

[0145]

[0146] The specific steps are:

[0147] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, p-fluorostyrene (24.43 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 35.3 mg, 71% yield) was obtained after spin drying.

[0148] The characterization data are as follows:

[0149] 1 H NMR (400 MHz, CDCl 3 )δ7.46-7.36(m,2H),7.15(t,J=8.4Hz,2H),6.09(dd,J=7.8,4.4Hz,1H),4.86-4.60(m,2H). 13 C NMR (101 MHz, CDCl 3 )δ163.7(d,J=251.5Hz),128.9(d,J=8.08Hz),128.8(d,J=4.04Hz),116.6(d,J=22.22Hz),79.93,71.18. 19 F NMR (376 MHz, CDCl 3 )δ-109.97.

[0150] Embodiment 18

[0151] The preparation of 1-(4-cyanophenyl)ethane-1,2-dinitrate is carried out according to the following reaction equation:

[0152]

[0153] The specific steps are:

[0154] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, p-cyanostyrene (24.43 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product was obtained after drying (colorless to light yellow liquid, 39.3 mg, 68% yield).

[0155] The characterization data are as follows:

[0156] 1 H NMR (400 MHz, CDCl 3 )δ7.76(d,J=8.4Hz,2H),7.56(d,J=8.4Hz,2H),6.14(dd,J=7.2,4.4Hz,1H),4.81-4.67(m,2H). 13 C NMR (101 MHz, CDCl 3 )δ137.9,133.2,127.4,117.9,114.3,79.5,70.7.

[0157] Embodiment 19

[0158] The preparation of 1-(4-bromophenyl)ethane-1,2-dinitrate is carried out according to the following reaction equation:

[0159]

[0160] The specific steps are:

[0161] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% aqueous nitric acid solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, p-bromostyrene (36.60 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The iodobenzene was washed out by column chromatography with n-pentane, and then the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 54.1 mg, 88% yield) was obtained after spin drying.

[0162] The characterization data are as follows:

[0163] 1 H NMR (400 MHz, CDCl 3 ): δ7.59(d,J=8.4Hz,2H),7.30(d,J=8.4Hz,2H),6.06(dd,J=6.8,5.1Hz,1H),4.76-4.67(m,2H). 13 C NMR (101 MHz, CDCl 3 ): δ132.7,131.9,128.4,124.6,79.9,71.0.

[0164] Embodiment 20

[0165] The preparation of 1-(4-trifluoromethylphenyl)ethane-1,2-dinitrate is carried out according to the following reaction equation:

[0166]

[0167] The specific steps are:

[0168] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, p-trifluoromethylstyrene (24.43 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 39.3 mg, 68% yield) was obtained after spin drying.

[0169] The characterization data are as follows:

[0170] 1 H NMR (400 MHz, CDCl 3 )δ7.73(d,J=8.0Hz,2H),7.56(d,J=8.0Hz,2H),6.16(t,J=6.0Hz,1H),4.74(d,J=5.6Hz,2H). 13 C NMR (101 MHz, CDCl 3 )δ136.88(d,J=1.01Hz),132.4(q,J=33.33Hz),127.20,126.5(q,J=4.04Hz),,123.5(q,J=273.7 1Hz),79.8,70.9.

[0171] Embodiment 21

[0172] The preparation of 1-o-chlorophenylethane-1,2-dinitrate is carried out according to the following reaction equation:

[0173]

[0174] The specific steps are:

[0175] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Then, p-chlorostyrene (27.72 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 40.1 mg, 76% yield) was obtained after spin drying.

[0176] The characterization data are as follows:

[0177] 1 H NMR (400 MHz, CDCl 3 )δ7.52-7.43(m,2H),7.42-7.34(m,2H),6.58(dd,J=8.,3.2Hz,1H),4.83-4.68(m,2H). 13 C NMR (101 MHz, CDCl 3 )δ132.5,131.0,130.8,130.2,127.8,127.1,77.0,69.8.

[0178] Embodiment 22

[0179] The preparation of 1,2-ethyl dinitrate is carried out according to the following reaction equation:

[0180]

[0181] The specific steps are:

[0182] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% aqueous nitric acid solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, a balloon filled with ethylene was inserted, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 10 mg, 34% yield) was obtained after spin drying.

[0183] The characterization data are as follows:

[0184] 1 H NMR (400 MHz, CDCl 3 )δ4.75(s,4H); 13 C NMR (101 MHz, CDCl 3 )δ68.3.

[0185] Embodiment 23

[0186] The preparation of (8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]benzanthrene-3-yl 6,7-bis(nitrooxy)heptanoate is carried out according to the following reaction formula:

[0187]

[0188] The specific steps are:

[0189] At room temperature, diacetoxyiodobenzene (64.42 mg, 0.2 mmol), 65% nitric acid aqueous solution (38.8 μl, 0.6 mmol) and 2 ml of dichloromethane were added to the reaction flask in sequence, and the reaction was stirred at 30°C for 30 minutes. Subsequently, a styrene substrate (76.11 mg, 0.2 mmol) was added, and the reaction was continued at 30°C for 6 hours. The dichloromethane was removed by rotary evaporation to obtain a purple-black oil. The iodobenzene was washed out by column chromatography with n-pentane, and the product was washed out with petroleum ether: ethyl acetate 15:1. The pure product (colorless to light yellow liquid, 10 mg, 34% yield) was obtained after spin drying.

[0190] The characterization data are as follows:

[0191] 1 H NMR (400 MHz, CDCl 3 )δ7.28(d,J=8.4Hz,1H),6.84(dd,J=8.4,2.4Hz,1H),6.80(s,1H),5.36-5.26(m,1H ),4.75(dd,J=12.8,3.2Hz,1H),4.48(dd,J=12.8,6.4Hz,1H),2.97-2.85(m,2H),2. 58(t,J=7.2Hz,2H),2.55-2.46(m,1H),2.44-2.37(m,1H),2.33-2.23(m,1H),2.20- 2.11(m,1H),2.11-1.91(m,3H),1.86-1.73(m,4H),1.69-1.39(m,8H),0.90(s,3H); 13 C NMR (101 MHz, CDCl 3 )δ172.0,148.5,138.2,137.6,126.5,121.5,118.7,78.9,71.2,50.5,48.0, 44.2,38.0,35.9,33.8,31.6,29.4,29.1,26.4,25.8,24.5,24.4,21.6,13.9.

[0192] The o-dinitrate of the present invention can be converted between functional groups, that is, the nitrate group of the o-dinitrate compound obtained by the present invention can be converted with other functional groups, such as hydroxyl or azide functional groups, for the development of explosives, plasticizers or other special materials. The following is an example of 1-(4-bromophenyl)ethane-1,2-dinitrate obtained in Example 19, which is described as follows:

[0193] Application Example 1:

[0194] The 1-(4-bromophenyl)ethane-1,2-dinitrate prepared in Example 19 was used to prepare 1-(4-bromophenyl)ethane-1,2-diol according to the following reaction equation:

[0195]

[0196] The specific operation steps are as follows: at room temperature, 1-(4-bromophenyl)ethane-1,2-dinitrate (61.01 mg, 0.2 mmol), zinc powder (130 mg, 20 mmol) and 2 ml of acetic acid were added to the reaction bottle in sequence, and the reaction was carried out at 0°C for 60 minutes. The product was flushed out by column chromatography with petroleum ether: ethyl acetate 15:1, and the pure product was obtained after spin drying (white solid, 39 mg, 90% yield).

[0197] The characterization data of the obtained product are as follows:

[0198] 1 H NMR (300 MHz, CDCl 3 ): δ7.49(d,J=8.4Hz,2H),7.25(d,J=8.4Hz,2H),4.79(dd,J=8.0,3.2Hz,1H),3.75(d,J=11.2Hz,1H),3.66–3.59(m,1H).

[0199] It can be seen that the o-dinitrate compounds prepared by the method of the present invention can simply and conveniently realize the conversion of functional groups with high yield.

[0200] Application Example 2:

[0201] The 1-(4-bromophenyl)ethane-1,2-dinitrate prepared in Example 19 was used to prepare 1-bromo-4-(1,2-diazideethyl)benzene according to the following reaction equation:

[0202]

[0203] The specific operation steps are: at room temperature, add 1-(4-bromophenyl)ethane-1,2-dinitrate (61.01 mg, 0.2 mmol), sodium azide (36 mg, 6 mmol) and 2 ml of dimethyl sulfoxide to the reaction bottle in sequence, react at 60°C for 10 hours, and flush out the product by column chromatography with petroleum ether: ethyl acetate 10:1. After spin drying, the pure product (colorless oil, 41 mg, 77% yield) was obtained.

[0204] The characterization data of the obtained product are as follows:

[0205] 1 H NMR (300 MHz, CDCl3 ): δ7.55(d,J=8.4Hz,2H),7.22(d,J=8.4Hz,2H),4.64(dd,J=8.0,5.2Hz,1H),3.45(qd,J=12.8,6.4Hz,2H).

[0206] It can be seen that the o-dinitrate compounds prepared by the method of the present invention can simply and conveniently realize the conversion of functional groups with high yield.

Claims

1. An o-dinitrate compound, characterized in that: The general formula is as follows: Among them, R, R 1 , R 2 , R 3 is alkyl, aryl or hydrogen.

2. The o-dinitrate compound according to claim 1, characterized in that The alkyl group includes 1-decyl, benzyl, 1-phenylethyl, 1-(CH2) n -Br or 1-(CH2) n -OOCAr; The aryl group includes phenyl, 4-chloromethylphenyl, 4-tert-butylphenyl, 4-acetoxyphenyl, 4-methoxycarbonylphenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 4-nitrophenyl, 4-fluorophenyl, 4-iodophenyl, 2,6-dichlorophenyl or 3,5-dichlorophenyl.

3. A method for preparing an o-dinitrate compound as claimed in claim 1 or 2, characterized in that: In an organic solvent, an in-situ generated non-cyclic periodinitiate nitrate reagent is used as a nitrate source, and olefins are directly added to the reaction system for reaction to generate ortho-dinitrate compounds.

4. The preparation method according to claim 3, characterized in that: The method is specifically as follows: at 25 to 35° C., in an air atmosphere, firstly, diacetyl iodobenzene and nitric acid are added to a solvent solution, stirred for 20 to 60 minutes to obtain a non-cyclic periodinitrate reagent, then olefin is added, and the reaction is continued for 5 to 8 hours. Finally, the reaction solution is concentrated and subjected to column chromatography to obtain a pure o-dinitrate product.

5. The preparation method according to claim 4, characterized in that: The molar ratio of diacetyl iodobenzene to nitric acid is 1:2-1:

3.

6. The preparation method according to claim 4, characterized in that: The volume concentration of the nitric acid is 60-70%.

7. The preparation method according to claim 4, characterized in that: The solvent is dichloromethane, 1,2-dichloroethane, toluene or chloroform.

8. The preparation method according to claim 4 or 7, characterized in that: The amount of the solvent used is 10 liters of solvent per mole of diacetyl iodobenzene.

9. The preparation method according to claim 4, characterized in that: The molar ratio of the olefin to the non-cyclic periodinitrate reagent is 1:(1.2-1.8).

10. A use of the o-dinitrate compound as claimed in claim 1, characterized in that: The o-dinitrate compounds are used to convert the nitrate group into other functional groups.

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