CN114436846B - Nitrate ester transfer reagent and preparation method and application thereof - Google Patents

Nitrate ester transfer reagent and preparation method and application thereof Download PDF

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CN114436846B
CN114436846B CN202210032363.8A CN202210032363A CN114436846B CN 114436846 B CN114436846 B CN 114436846B CN 202210032363 A CN202210032363 A CN 202210032363A CN 114436846 B CN114436846 B CN 114436846B
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nitrate
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transfer reagent
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aryl iodide
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CN114436846A (en
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邓清海
成轩
殷权
江岭峰
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Shanghai Normal University
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    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/02—Preparation of esters of nitric acid
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    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C205/11—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings
    • C07C205/12—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings the six-membered aromatic ring or a condensed ring system containing that ring being substituted by halogen atoms
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    • C07C67/00—Preparation of carboxylic acid esters
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    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
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    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
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Abstract

The invention relates to a nitrate ester transfer reagent and a preparation method and application thereof, in particular to a novel organic acyclic trivalent iodine nitrate ester transfer reagent and a preparation method thereof. The nitrate radical transfer reagent has a general formula:

Description

Nitrate ester transfer reagent and preparation method and application thereof
Technical Field
The invention relates to the field of organic synthetic chemistry, in particular to a nitrate radical transfer reagent compound and a synthetic method thereof, and especially relates to a novel aryl acyclic trivalent iodine nitrate radical transfer reagent, a preparation method thereof and application of the reagent in the field of organic synthetic methodologies.
Background
The nitrate compound not only has wide application in the fields of petrochemical industry, material science, military field, dye, sugar production and the like; it is used as the most common donor of Nitric Oxide (NO), has wide application in treating cardiovascular, immune and nervous system diseases and is also potential antitumor medicine. Among the drugs commonly used in clinic are Nitroglycerin (NTG), isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), nipradilol (Nipradilol), nicotidil (Nicorandil), and the like. In addition, it was found that the introduction of nitrate functional groups into drug molecules can greatly reduce drug toxicity and toxic side effects (Mini Reviews in Medicinal Chemistry,2001,1,57-70). Therefore, how to introduce nitrate functional groups into molecules with high efficiency is an important research topic.
Regarding the preparation of nitrate compounds, the industrial process mainly uses strong acid nitration of alcohol, usually uses concentrated nitric acid as nitrating agent to realize the nitration of alcohol, and the strong oxidizing property of concentrated nitric acid makes the nitric acid have poor compatibility with substrates, and the post-treatment of the reaction has serious harm to the environment (Journal of the American Pharmaceutical Association,1958,47,368). In recent years, many chemists have also started to address the synthesis of nitrate compounds. Sources of nitrate esters can be classified into the following three categories: the first type is to use nitric acid or nitrate as nitrate source. In 2019, igor group of university of Columbia Andbis synthesized benzyl nitrate by a pre-diazotization strategy of benzyl phenylacetate using ferric nitrate as nitrate source (org. Lett.2019,21, 6909-6913). The second is to provide the nitrate source as tert-butyl nitrite or sodium nitrite and oxygen. Kang Yanbiao subject group of university of science and technology in 2016 uses allyloxime as substrate at TBN +.O 2 Nitrate containing isoxazole skeleton was synthesized in the system (adv. Synth. Catalyst., 2016,358,1942-1945). The third class is that of nitrate transfer reagents represented by cyclic trivalent iodides with o-iodobenzoic acid as a backbone, which are nitrate sources but which can only be used for the nitrosation of 1, 3-dicarbonyl compounds (Heterocycles, 1996,42,47; angel. Chem., int.Ed.,2020,59,17162;Org.Chem.Front, 2020,7,3509).
In summary, by comparing various nitrate synthesis methods, it was found that: the existing nitrate synthesis generally has the problems of poor atom economy, poor selectivity, narrow substrate application range, low safety, complex post-treatment process, serious material waste and the like.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a nitrate ester transfer reagent, a preparation method and application thereof. Aims at breaking through the limitation of the prior art on raw materials and substrates, developing a new reagent which is more efficient, green, safe and capable of preparing a large number of nitrate compounds, and developing the application of the reagent in the nitrate radical transfer reaction under the condition of no catalyst based on the high reaction activity of the trivalent iodine nitrate radical transfer reagent.
The aim of the invention can be achieved by the following technical scheme: a nitrate transesterification reagent having the structure:
wherein r=hydrogen, halogen, alkyl, alkoxycarbonyl, acyl, aryl, trifluoromethyl, cyano, nitro or alkoxy.
Further preferably, the nitric acid transesterification reagent is structured as follows:
wherein r=hydrogen, 4-fluoro, 3-chloro, 3-bromo, 2-bromo, 4-methyl, 4-methoxycarbonyl, 4-ethoxycarbonyl, 4-acetyl, 4-phenyl, 4-trifluoromethyl, 4-cyano, 4-nitro or 4-methoxy.
The invention also provides a preparation method of the nitrate radical transfer reagent, which comprises the following steps: the method is characterized in that a dichloro aryl iodide compound 2 and silver nitrate are used as raw materials, a ligand exchange reaction is carried out to obtain a bis (aryl iodide) nitrate compound 4, and the bis (aryl iodide) nitrate compound 4 is hydrolyzed to obtain a nitrate ester transfer reagent 1, wherein the reaction formula is as follows:
wherein r=hydrogen, halogen, alkyl, alkoxycarbonyl, acyl, aryl, trifluoromethyl, cyano, nitro or alkoxy.
The preparation of the nitrate radical transfer reagent 1 specifically comprises the following steps: dissolving the dichloroaryl iodide compound 2 into an organic solvent in a nitrogen atmosphere at room temperature, adding silver nitrate, stirring for 3-8 hours, filtering to remove silver chloride, obtaining a concentrated solution of the compound 4, adding a proper amount of water, and stirring for 5-30 minutes to obtain the nitrate radical transfer reagent 1.
The organic solvent is dichloromethane;
the mol ratio of the dichloro aryl iodide compound 2 to the silver nitrate is 1:2.5-1:3.5;
the amount of water used was 0.5 l/mol of compound 2.
The dichloro aryl iodide compound 2 is synthesized by the following method: the method takes aryl iodide compound 3 and sodium hypochlorite as raw materials, and the dichloro aryl iodide compound 2 can be obtained through oxidation reaction, and the steps are as follows:
wherein r=hydrogen, halogen, alkyl, alkoxycarbonyl, acyl, aryl, trifluoromethyl, cyano, nitro or alkoxy.
The synthesis method of the dichloro aryl iodide compound 2 specifically comprises the following steps: at room temperature, the aryl iodide compound 3 is dissolved in an organic solvent, sodium hypochlorite, water and concentrated hydrochloric acid are sequentially added under the condition of stirring, stirring reaction is carried out for 0.5-2 hours, and the dichloro aryl iodide compound 2 can be obtained after filtration, water washing and drying.
The organic solvent is acetonitrile, and the volume ratio of acetonitrile to water is 1:1-1:2.
The dosage of the concentrated hydrochloric acid is 2 liters per mole based on 3 moles of aryl iodides; the amount of the sodium hypochlorite is 2 liters per mole, and the concentration of the hypochlorous acid is 10 weight percent.
The invention also provides application of the nitrate ester transfer reagent, wherein the nitrate ester transfer reagent 1 is used as a nitrate ester transfer reagent to carry out metal-free catalytic nitrate esterification reaction of various organic matters.
Compared with the prior art, the invention has the following beneficial effects:
1. the invention designs and synthesizes a novel aryl non-cyclic trivalent iodinated ester transfer reagent, which has the structure of non-cyclic trivalent iodized ether with an iodine-oxygen-iodine framework, and the reagent takes easily available aryl iodine (such as iodobenzene) as a starting material, and can obtain a high-purity product through two-step reaction and crystallization, thereby avoiding column chromatography, and having simple and convenient operation and high synthesis efficiency. When the reagent reacts, the aryl iodide obtained after giving the nitrate radical can be continuously recycled, and the reagent is environment-friendly. Can overcome the defects of harsh reaction conditions, dangerous reagent use, complicated dangerous post-treatment, limited applicable substrates and the like of the traditional technology for synthesizing the nitrate compound.
2. The invention provides a new way for efficiently introducing nitrate functional groups into molecules, provides a new method for synthesizing a large amount of aryl non-cyclic trivalent iodine reagent and nitrate compounds and widely applying the aryl non-cyclic trivalent iodine reagent and the nitrate compounds, and has remarkable expected social benefit and economic benefit.
3. The aryl non-cyclic trivalent iodine nitrate transfer reagent provided by the invention has good stability and high reaction activity. The pure product has good reaction effect after being stored for one year at room temperature, and is decomposed into aryl iodine only by a small amount after being stored in deuterated chloroform for one week; compared with the cyclic trivalent iodine nitrate transfer reagent, the phenyl acyclic trivalent iodine nitrate transfer reagent provided by the invention has higher activity, and can perform a plurality of reactions under the condition of no metal catalysis.
Detailed Description
The following describes in detail the examples of the present invention, which are implemented on the premise of the technical solution of the present invention, and detailed embodiments and specific operation procedures are given, but the scope of protection of the present invention is not limited to the following examples.
All solvents, iodobenzene, sodium hypochlorite, concentrated hydrochloric acid, silver nitrate, used in the examples below were purchased from commercial sources.
Example 1
Preparation of phenyl acyclic trivalent iodinated ester transfer reagent, the reaction was carried out according to the following reaction equation:
the specific operation steps are as follows:
1) Compound 3a (iodobenzene, 12.2 g, 0.06 mol) was dissolved in 200 ml acetonitrile at room temperature, sodium hypochlorite (10 wt%,120 ml), water (200 ml) and analytically pure concentrated hydrochloric acid (120 ml) were added in turn under stirring, and the mixture was stirred for 1 hour, filtered, washed with water and dried to obtain dichloroiodobenzene 2a (14.7 g, 89% yield);
2) Compound 2a (dicloroiodobenzene, 13.8 g, 0.05 mol) was dissolved in 300 ml of dichloromethane under nitrogen atmosphere at room temperature, silver nitrate (25.5 g, 0.15 mol) was added, stirred overnight, the silver chloride was removed by filtration, the yellow oil was concentrated, after dissolving in 50 ml of dichloromethane, a proper amount of water (0.5 l/mol) was added and stirred for 30 minutes to obtain a nitrate transesterification reagent compound 1a (10.7 g, 78% yield) as a yellow solid; characterization data are as follows:
1 H NMR(400MHz,CDCl 3 ):δ7.91(d,J＝8.0Hz,4H),7.64(t,J＝7.6Hz,2H),7.48(t,J＝8.0Hz,2H)； 13 C{ 1 H}NMR(101MHz,CD 3 CN):δ135.3,133.8,132.4,125.0；IR(KBr,cm -1 ):3056,2399,1677,1470,1384,994,732,681；HRMS(ESI,m/z):calcd for C 12 H 10 I 2 NO 4 + [M-NO 3 - ] + :485.8694；found 485.8650；Elemental Analysis:calcd(％)for C 12 H 10 I 2 N 2 O 7 :[C]26.30,[H]1.84,[I]46.31,[N]5.11,[O]20.44；found[C]25.59,[H]1.93,[N]5.01,[O]20.78。
from the above characterization test, it was confirmed that compound 1a obtained by the method described in example 1 had the above structure.
Example 2
Preparation of p-fluorophenyl acyclic trivalent iodinated ester transfer reagent, according to the following reaction equation:
the specific operation steps are as follows:
1) Dissolving compound 3b (0.005 mol) in 20 ml of acetonitrile at room temperature, adding sodium hypochlorite (10 wt%,10 ml), water (20 ml) and analytically pure concentrated hydrochloric acid (10 ml) in sequence under stirring, stirring for reacting for 1 hour, filtering, washing with water, and drying to obtain the dichloroiodobenzene 2b (71% yield);
2) Compound 2b (0.003 mol) was dissolved in 20 ml of methylene chloride under nitrogen atmosphere at room temperature, silver nitrate (0.09 mol) was added thereto, and the mixture was stirred overnight, the silver chloride was removed by filtration, and a yellow oil was obtained by concentration, and after dissolving in 10 ml of methylene chloride, a drop of water was added thereto and stirring was carried out for 10 minutes, to obtain a nitrate transesterification reagent compound 1b (64% yield) as a yellow solid; characterization data are as follows:
1 H NMR(400MHz,CD 3 CN):δ8.55-7.95(m,4H),7.68-6.94(m,4H)； 13 C{ 1 H}NMR(101MHz,CD 3 CN):δ165.5(J C-F ＝253.8Hz),138.2(J C-F ＝9.2Hz),119.6(J C-F ＝23.3Hz)；IR(KBr,cm -1 ):3091,2399,1766,1576,1481,1383,1230,822,716；HRMS(ESI,m/z):calcd for C 12 H 8 F 2 I 2 NO 4 + [M-NO 3 - ] + :521.8505；found 521.8514。
from the above characterization test, it was confirmed that compound 1b obtained by the method described in example 2 had the above structure.
Example 3
The preparation of the m-chlorophenyl non-cyclic trivalent iodine nitrate transfer reagent is carried out according to the following reaction equation:
the specific operation steps are as follows:
1) Dissolving compound 3c (0.005 mol) in 20 ml of acetonitrile at room temperature, adding sodium hypochlorite (10 wt%,10 ml), water (20 ml) and analytically pure concentrated hydrochloric acid (10 ml) in sequence under stirring, stirring for reacting for 1 hour, filtering, washing with water, and drying to obtain the dichloroiodobenzene 2c (60% yield);
2) Compound 2c (0.003 mol) was dissolved in 20 ml of methylene chloride under nitrogen atmosphere at room temperature, silver nitrate (0.09 mol) was added thereto, and stirred overnight, silver chloride was removed by filtration, and concentrated to give a yellow oil, which was dissolved in 10 ml of methylene chloride, and then added with a drop of water and stirred for 10 minutes to give a nitrate transesterification reagent compound 1c (86% yield) as a yellow solid; characterization data are as follows:
1 H NMR(400MHz,CD 3 CN):δ8.12-7.82(m,4H),7.59(d,J＝8.0Hz,2H),7.45(t,J＝8.0Hz,2H)； 13 C{ 1 H}NMR(101MHz,CD 3 CN):δ136.5,134.4,133.9,133.5,133.4；IR(KBr,cm -1 ):3149,3088,2398,1765,1563,1454,1382,1285,772,741；HRMS(ESI,m/z):calcd for C 12 H 8 Cl 2 I 2 NO 4 + [M-NO 3 - ] + :553.7914；found 553.7921。
from the above characterization test, it was confirmed that compound 1c obtained by the method described in example 3 had the above structure.
Example 4
The preparation of the o-bromophenyl acyclic trivalent iodinated ester transfer reagent is carried out according to the following reaction equation:
the specific operation steps are as follows:
1) Dissolving compound 3d (0.005 mol) in 20 ml of acetonitrile at room temperature, adding sodium hypochlorite (10 wt%,10 ml), water (20 ml) and analytically pure concentrated hydrochloric acid (10 ml) in sequence under stirring, stirring for reacting for 1 hour, filtering, washing with water, and drying to obtain dichloroiodobenzene 2d (79% yield);
2) Compound 2d (0.003 mol) was dissolved in 20 ml of methylene chloride under nitrogen atmosphere at room temperature, silver nitrate (0.09 mol) was added thereto, and the mixture was stirred overnight, the silver chloride was removed by filtration, and a yellow oil was obtained by concentration, and after dissolving in 10 ml of methylene chloride, a drop of water was added thereto and stirring was carried out for 10 minutes, to obtain a nitrate transesterification reagent compound 1d (62% yield) as a yellow solid; characterization data are as follows:
1 H NMR(400MHz,CD 3 CN):δ8.12(s,2H),7.82(s,2H),7.51(s,2H),7.37(s,2H)； 13 C{ 1 H}NMR(101MHz,CD 3 CN):δ139.4,136.1,134.4,131.2,127.5；IR(KBr,cm -1 ):3055,2399,1766,1437,1368,1001,745；HRMS(ESI,m/z):calcd for C 12 H 8 Br 2 I 2 NO 4 + [M-NO 3 - ] + :641.6904；found 641.6911；Elemental Analysis:calcd(％)for C 12 H 8 Br 2 I 2 N 2 O 7 :[C]20.42,[H]1.14；[Br]22.64,[I]35.96,[N]3.97,[O]15.87；found[C]20.24,[H]1.22,[N]3.84,[O]16.18。
from the above characterization test, it was confirmed that compound 1d obtained by the method described in example 4 had the above structure.
Example 5
Preparation of p-ethoxycarbonylphenyl acyclic trivalent iodinated nitrate transfer reagent, the reaction is carried out according to the following reaction equation:
the specific operation steps are as follows:
1) Dissolving compound 3e (0.005 mol) in 20 ml of acetonitrile at room temperature, adding sodium hypochlorite (10 wt%,10 ml), water (20 ml) and analytically pure concentrated hydrochloric acid (10 ml) in sequence under stirring, stirring for reacting for 1 hour, filtering, washing with water, and drying to obtain the dichloroiodobenzene 2e (69% yield);
2) Compound 2e (0.003 mol) was dissolved in 20 ml of methylene chloride under nitrogen atmosphere at room temperature, silver nitrate (0.09 mol) was added thereto, and the mixture was stirred overnight, the silver chloride was removed by filtration, and a yellow oil was obtained by concentration, and after dissolving in 10 ml of methylene chloride, a drop of water was added thereto and stirring was carried out for 10 minutes, to obtain a nitrate transesterification reagent compound 1e (95% yield) as a yellow solid; characterization data are as follows:
1 H NMR(400MHz,CDCl 3 ):δ7.90(s,8H),4.40(q,J＝7.6Hz,4H),1.41(t,J＝7.6Hz,6H)； 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ164.5,134.3,134.2,132.2,127.3,62.19,14.3；IR(KBr,cm -1 ):3065,2981,2399,1766,1720,1587,1355,1286,1270,1103,1008,753；HRMS(ESI,m/z):calcd for C 18 H 18 I 2 NO 8 + [M-NO 3 - ] + :629.9116；found 629.9122。
from the above characterization test, it was confirmed that compound 1e obtained by the method described in example 5 had the above structure.
Example 6
Preparation of the p-cyanophenyl acyclic trivalent iodinated ester transfer reagent, the reaction was carried out according to the following reaction equation:
the specific operation steps are as follows:
1) Dissolving compound 3f (0.005 mol) in 20 ml of acetonitrile at room temperature, adding sodium hypochlorite (10 wt%,10 ml), water (20 ml) and analytically pure concentrated hydrochloric acid (10 ml) in sequence under stirring, stirring for reacting for 1 hour, filtering, washing with water, and drying to obtain the dichloroiodobenzene 2f (69% yield);
2) Compound 2f (0.003 mol) was dissolved in 20 ml of methylene chloride under nitrogen atmosphere at room temperature, silver nitrate (0.09 mol) was added thereto, and the mixture was stirred overnight, the silver chloride was removed by filtration, and a yellow oil was obtained by concentration, and after dissolving in 10 ml of methylene chloride, a drop of water was added thereto and stirring was carried out for 10 minutes, to obtain a nitrate transesterification reagent compound 1f (64% yield) as a yellow solid; characterization data are as follows:
1 H NMR(400MHz,CD 3 CN):δ8.21(s,4H),7.86(s,4H)； 13 C{ 1 H}NMR(101MHz,CD 3 CN):δ135.6；IR(KBr,cm -1 ):3092,2400,1766,1570,1514,1353,850,735；HRMS(ESI,m/z):calcd for C 14 H 8 I 2 N 3 O 4 + [M-NO 3 - ] + :535.8599；found 535.8602。
from the above characterization test, it was confirmed that compound 1f obtained by the method described in example 6 had the above structure.
Example 7
Preparation of p-nitrophenyl acyclic trivalent iodinated ester transfer reagent, the reaction is carried out according to the following reaction equation:
the specific operation steps are as follows:
1) 3g (0.005 mol) of the compound is dissolved in 20 ml of acetonitrile at room temperature, sodium hypochlorite (10 wt%,10 ml), water (20 ml) and analytically pure concentrated hydrochloric acid (10 ml) are sequentially added under stirring, and the mixture is stirred and reacted for 1 hour, and 2g (65% yield) of the dichloroiodobenzene is obtained after filtration, water washing and drying;
2) 2g (0.003 mol) of the compound was dissolved in 20 ml of methylene chloride under nitrogen atmosphere at room temperature, silver nitrate (0.09 mol) was added thereto, and the mixture was stirred overnight, filtered to remove silver chloride, and concentrated to give a yellow oil, which was dissolved in 10 ml of methylene chloride, and then added with a drop of water and stirred for 10 minutes to give 1g (66% yield) of the compound as a nitrate transesterification reagent as a yellow solid; characterization data are as follows:
1 H NMR(400MHz,CD 3 CN):δ8.11(s,8H)； 13 C{ 1 H}NMR(101MHz,CD 3 CN):δ150.7,139.8,126.9,125.9；IR(KBr,cm -1 ):3065,2981,2399,1766,1720,1587,1355,1286,1270,1103,1008,753；HRMS(ESI,m/z):calcd for C 12 H 8 I 2 N 3 O 8 + [M-NO 3 - ] + :575.8395；found 575.8394。
from the above characterization test, it was confirmed that 1g of the compound obtained by the method described in example 7 had the above structure.
The compound 1a obtained in the method of example 1 is used as a transfer reagent of nitrate groups to carry out metal-free catalytic nitrate esterification reaction of various types of organic matters, and the effect is verified as follows:
test example 1: nitric esterification of beta-ketoesters
The specific operation steps are as follows: beta-ketoester S1a (0.2 mmol,1.0 equiv.) was then added to the phenyl acyclic trivalent iodinated transesterification reagent 1a (0.11 mmol,0.55 equiv.) obtained in example 1, followed by CH 2 Cl 2 (2 mL) is added into a reaction tube, stirred at room temperature and reacted for 1 minute, after TLC detection is finished, petroleum ether/ethyl acetate is used as eluent, and silica gel (200-300 meshes) is adopted for column chromatography purification to obtain a nitric acid esterification product S1b, and the yield is 99 percent (64.0 mg) and is white solid; the characterization is as follows:
1 H NMR(400MHz,CDCl 3 ):δ7.75(d,J＝8.4Hz,1H),6.97(dd,J＝2.4,8.4Hz,1H),6.92(s,1H),4.18(d,J＝17.6Hz,1H),3.92(s,3H),3.33(d,J＝17.6Hz,1H),1.45(s,9H)。
test example 2: nitric esterification of beta-keto amides
The specific operation steps are as follows: beta-ketoamide S2a (0.2 mmol,1.0 equiv.) was reacted with phenyl acyclic trivalent iodine nitrate transesterification reagent 1a (0.11 mmol,0.55 equiv.) obtained in example 1, followed by CH 2 Cl 2 (2 mL) was added to the reaction tube, stirred at room temperature for 1 minute, and after completion of TLC detection, purified by column chromatography on silica gel (200-300 mesh) using petroleum ether/ethyl acetate as eluent to give the nitrate product S2b in 74% yield (52.7 mg) as a white solid; the characterization is as follows:
1 H NMR(400MHz,CDCl 3 ):δ7.77-7.72(m,1H),7.37-7.22(m,5H),7.00-6.93(m,2H),6.81(s,1H),4.55-4.47(m,1H),4.45-4.33(m,1H),3.92(s,3H),3.28(d,J＝17.6Hz,1H)。
test example 3: nitric acid esterification of 1, 3-diones
The specific operation steps are as follows: 1, 3-Dione S3a (0.2 mmol,1.0 equiv.) was sequentially reacted with phenyl acyclic trivalent iodine nitrate transesterification reagent 1a (0.11 mmol,0.55 equiv.) obtained in example 1, and CH 2 Cl 2 (2 mL) was added to the reaction tube, stirred at room temperature for 10 minutes, and after completion of TLC detection, purified by column chromatography on silica gel (200-300 mesh) using petroleum ether/ethyl acetate as eluent to give the product S3b in 82% yield (53.7 mg) as a white solid; the characterization is as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.32(d,J＝8.8Hz,2H),7.77(d,J＝8.0Hz,1H),7.73(t,J＝7.8Hz,1H),7.57(d,J＝7.8Hz,1H),7.44(t,J＝7.8Hz,1H),6.97(d,J＝9.2Hz,2H),4.52(d,J＝16.8Hz,1H),3.88(s,3H),3.35(d,J＝16.8Hz,1H)； 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ192.5,188.2,164.3,151.7,137.2,132.8,132.6,128.7,126.4,126.1,125.9,114.1,97.6,55.7,38.8；HRMS(ESI,m/z):calcd for C 17 H 14 NO 6 + [M+H] + :328.0816；found 328.0811。
test example 4: dearomatization and nitric esterification of beta-naphthol
The specific operation steps are as follows: beta-naphthol S4a (0.2 mmol,1.0 equiv.) and phenyl acyclic trivalent iodinated transesterification reagent 1a obtained in example 1 (0.11 mmol,0.55 equiv.) were sequentially added to CH 2 Cl 2 (2 mL) was added to the reaction tube, stirred at room temperature for 30 minutes, and after completion of TLC detection, the reaction was purified by column chromatography using petroleum ether/ethyl acetate as eluent and silica gel (200-300 mesh) to give the nitrate product S4b in 71% yield (60.8 mg) as a yellow solid; the characterization is as follows:
1 H NMR(400MHz,CDCl 3 ):δ7.61(d,J＝10.0Hz,1H),7.48-7.42(m,1H),7.40-7.33(m,5H),7.33-7.28(m,1H),7.21(t,J＝7.2Hz,1H),7.15(d,J＝7.6Hz,1H),7.07(t,J＝7.6Hz,1H),7.02-6.92(m,1H),6.52(d,J＝7.6Hz,1H),6.10(d,J＝10.0Hz,1H),5.00(d,J＝16.0Hz,1H),4.86(s,2H),4.47(d,J＝16.0Hz,1H)； 13 C{ 1 H}NMR(101MHz,CDCl 3 ):δ197.6,167.8,147.2 143.7,136.5,135.9,130.9,130.8,130.4,130.1,129.6,128.9,128.2,128.1,127.76,127.71,127.69,127.59,125.9,123.2,64.1,50.8,50.7；HRMS(ESI,m/z):calcd for C 25 H 21 N 2 O 5 + [M+H] + :429.1445；found 429.1448。

Claims (7)

1. a method for preparing a nitrate radical transfer reagent, which is characterized by comprising the following steps: the method is characterized in that a dichloro aryl iodide compound 2 and silver nitrate are used as raw materials, a ligand exchange reaction is carried out to obtain a bis (aryl iodide) nitrate compound 4, and the bis (aryl iodide) nitrate compound 4 is hydrolyzed to obtain a nitrate ester transfer reagent 1, wherein the reaction formula is as follows:
；
wherein r=hydrogen, 4-fluoro, 3-chloro, 3-bromo, 2-bromo, 4-methyl, 4-methoxycarbonyl, 4-ethoxycarbonyl, 4-acetyl, 4-phenyl, 4-trifluoromethyl, 4-cyano, 4-nitro or 4-methoxy.
2. The method for preparing the nitrate ester transfer reagent according to claim 1, wherein the preparation of the nitrate ester transfer reagent 1 specifically comprises the following steps: dissolving the dichloroaryl iodide compound 2 into an organic solvent in a nitrogen atmosphere at room temperature, adding silver nitrate, stirring for 3-8 hours, filtering to remove silver chloride, obtaining a concentrated solution of the compound 4, adding a proper amount of water, and stirring for 5-30 minutes to obtain the nitrate radical transfer reagent 1.
3. The method for preparing a nitrate radical transfer reagent according to claim 1 or 2, wherein the organic solvent is methylene chloride;
the mol ratio of the dichloro aryl iodide compound 2 to the silver nitrate is 1:2.5-1:3.5;
the amount of water used was 0.5 l/mol of compound 2.
4. The method for preparing the nitrate radical transfer reagent according to claim 1 or 2, wherein the dichloroaryl iodide compound 2 is synthesized by the following method: the method takes aryl iodide compound 3 and sodium hypochlorite as raw materials, and the dichloro aryl iodide compound 2 can be obtained through oxidation reaction, and the steps are as follows:
；
wherein r=hydrogen, 4-fluoro, 3-chloro, 3-bromo, 2-bromo, 4-methyl, 4-methoxycarbonyl, 4-ethoxycarbonyl, 4-acetyl, 4-phenyl, 4-trifluoromethyl, 4-cyano, 4-nitro or 4-methoxy.
5. The method for preparing a nitrate radical transfer reagent according to claim 4, wherein the synthesis method of the dichloroaryl iodide compound 2 is specifically as follows: at room temperature, the aryl iodide compound 3 is dissolved in an organic solvent, sodium hypochlorite, water and concentrated hydrochloric acid are sequentially added under the condition of stirring, stirring reaction is carried out for 0.5-2 hours, and the dichloro aryl iodide compound 2 can be obtained after filtration, water washing and drying.
6. The method for preparing a nitrate radical transfer reagent according to claim 5, wherein the organic solvent is acetonitrile, and the volume ratio of acetonitrile to water is 1:1-1:2.
7. The method for producing a nitrate ester transfer agent according to claim 5, wherein the amount of the concentrated hydrochloric acid is 2 liters per mole based on 3 moles of the aryl iodide; the dosage of the sodium hypochlorite is 2 liters per mole, and the concentration of the hypochlorous acid is 10wt percent.
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