A method for synthesizing deuterated nitromethane based on continuous flow photocatalysis technology

Abstract

The application provides a deuterated nitromethane synthesis method based on a continuous flow photocatalysis technology. The method uses deuterated methane obtained in a Fischer-Tropsch synthesis or an electrocatalytic reduction of CO2 as a raw material, and realizes direct nitration in a continuous flow microreactor under the joint action of an iron-based photocatalyst and specific wavelength light. The reaction effectively inhibits side reactions such as over-nitration, so that the selectivity of the deuterated nitromethane reaches more than 90%, and the product has high purity. The method uses an iron-based photocatalytic system to realize direct nitration of deuterated methane under ultraviolet light and / or visible light irradiation, has the advantages of safe and reliable process, recyclable use and the like, and is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the technical field of deuterated reagent preparation, specifically relating to a method for synthesizing deuterated nitromethane based on continuous flow photocatalysis technology. Background Technology

[0002] Deuterated nitromethane is an important deuterated labeling reagent and synthetic building block, widely used in basic research and drug development: in mechanistic studies, it serves as a deuterated probe to track reaction pathways; in the pharmaceutical field, it is a key starting material for deuterated drugs (such as deuterated lexicitinib and donafenib), improving the metabolic stability and efficacy of drugs through deuterium atoms; it is also used as a nuclear magnetic resonance solvent or an internal standard for chromatography-mass spectrometry.

[0003] Currently, the industrial production of deuterated nitromethane mainly adopts the route of "first preparing nitromethane, then through hydrogen-deuterium exchange," that is, nitromethane and deuterium water exchange stepwise under catalytic conditions to obtain a product with a high deuteration rate. However, this route is highly dependent on a stable supply of nitromethane, and the industrial production of nitromethane itself has obvious bottlenecks: First, the substitution method (such as the reaction of dimethyl sulfate and nitrite) is simple to operate, but the raw materials are highly toxic and produce a lot of inorganic salt byproducts, resulting in significant environmental and cost pressures (see patent CN102659602, etc.); Second, the gas-phase nitration method (the reaction of alkanes and nitric acid under high temperature and pressure) has lower raw material costs, but the product selectivity is poor, the conditions are harsh, equipment corrosion is severe, and safety risks are high (see patent CN102574770, etc.).

[0004] On the other hand, deuterated methane, as a specialty gas, can be produced as a byproduct of Fischer-Tropsch synthesis or by the electrocatalytic reduction of heavy water (D2O). Angew. Chem. - Int. Ed 2025, 64 (e202511459.), but its high-value applications are currently extremely limited, only seen in the preparation of deuterated chloroform (CN 119462324). The technology for directly converting deuterated methane into deuterated nitromethane remains to be developed. The core challenge of this conversion lies in the fact that the C–D bond energy is higher than that of the C–H bond, making it more inert and difficult to achieve mild and highly selective nitration under conventional conditions. Furthermore, traditional batch photocatalysis suffers from low mass transfer efficiency, insufficient photon utilization, difficulty in controlling reaction conditions, and high scale-up risks.

[0005] Therefore, there is an urgent need in this field to develop a new method that can directly and efficiently convert deuterated methane into high-value-added deuterated nitromethane, which has clear economic and technological value. Summary of the Invention

[0006] This invention aims to develop a novel method for the direct and efficient conversion of deuterated methane into high-value-added deuterated nitromethane. Specifically, it relates to a method for synthesizing deuterated nitromethane based on continuous flow photocatalysis technology. This method utilizes an iron-based photocatalytic system to achieve the direct nitration of deuterated methane under ultraviolet and / or visible light irradiation, thereby efficiently preparing deuterated nitromethane.

[0007] In a first aspect of the invention, a method for synthesizing deuterated nitromethane based on continuous flow photocatalysis technology is provided, the method comprising the steps of: (1) Continuous supply and mixing of raw materials: (a) deuterated methane gas and (b) homogeneous reaction liquid are provided, wherein the homogeneous reaction liquid contains nitrating agent, additive, iron-based photocatalyst and solvent; (a) and (b) are continuously fed into a continuous flow microchannel reactor, thereby forming a gas-liquid two-phase reaction system in the liquid phase of the deuterated methane gas. (2) Continuous flow photocatalytic nitration reaction: The gas-liquid two-phase reaction system obtained in step (1) is subjected to photocatalytic nitration reaction in a microchannel reactor under ultraviolet light and / or visible light irradiation to generate reaction effluent containing deuterated nitromethane; (3) Recovery of deuterated methane and collection and purification of products: The reaction effluent obtained in step (2) is separated to obtain a gas phase rich in unreacted deuterated methane and a liquid phase containing deuterated nitromethane. The liquid phase is separated and purified to obtain the deuterated nitromethane product. The nitrating agent is an aqueous solution of nitric acid, fuming nitric acid, or a nitrification system composed of nitrate and protic acid; The iron-based photocatalyst is an iron salt or iron complex selected from the group consisting of: ferric chloride FeCl3, ferric bromide FeBr3, ferric trifluoromethanesulfonate Fe(OTf)3, ferric trifluoroacetate Fe(TFA)3, ferric sulfate Fe2(SO4)3, ferric nitrate Fe(NO3)3, ferric phosphate FePO4, ferric tetrafluoroborate Fe(BF4)3, ferric perchlorate Fe(ClO4)3, ferric oxalate Fe2(C2O4)3, ferric acetylacetone Fe(acac)3, ferric p-toluenesulfonate Fe(OTs)3, ferric ethylenediaminetetraacetic acid, and corresponding ferrous salts and their anhydrous / hydrated forms or corresponding iron complexes, or combinations thereof; The additives include chloride ion sources and / or nitrites; The wavelength of the ultraviolet and / or visible light is 300 nm to 780 nm.

[0008] In another preferred embodiment, the partial pressure of deuterated methane is 1 to 50 bar (absolute pressure), more preferably 10 to 20 bar.

[0009] In another preferred embodiment, the nitrating agent is an aqueous solution of nitric acid or fuming nitric acid, preferably an aqueous solution of nitric acid with a mass fraction of 60-75 wt.%, and more preferably an aqueous solution of nitric acid with a mass fraction of 68 wt.%.

[0010] In another preferred embodiment, the ferrous salt is selected from the group consisting of FeCl2, FeBr2, and FeSO4.

[0011] In another preferred embodiment, the iron-based photocatalyst is selected from the group consisting of FeCl3, FeCl2, Fe(ClO4)3, Fe(NO3)3, Fe(BF4)3, or combinations thereof.

[0012] In another preferred embodiment, the continuous flow microchannel reactor comprises one or more microchannel reactors connected in series.

[0013] In another preferred embodiment, (a) and (b) are respectively fed into the continuous flow microchannel reactor via their respective independent delivery systems.

[0014] In another preferred embodiment, the iron-based photocatalyst further includes a ligand selected from the group consisting of pyridines, bipyridines, terpyridines, tetrapyridines, phenanthroline compounds, Py-Box compounds, tetraphenylporphyrins and their derivatives, or combinations thereof.

[0015] In another preferred embodiment, the ligand is a bipyridine ligand.

[0016] In another preferred embodiment, the iron-based photocatalyst can be pre-synthesized and then added, or it can be formed by the in-situ complexation of iron salt and ligand in the reaction system.

[0017] In another preferred embodiment, the iron-based photocatalyst is formed by in-situ complexation of an iron salt and a ligand in the reaction system, wherein the iron salt is selected from the group consisting of FeCl3, FeCl2, Fe(ClO4)3, Fe(NO3)3, and Fe(BF4)3, and the ligand is selected from the group consisting of pyridines, bipyridines, terpyridines, tetrapyridines, phenanthroline compounds, Py-Box compounds, tetraphenylporphyrins and their derivatives, or combinations thereof.

[0018] In another preferred embodiment, the molar ratio of the iron salt / iron complex to the ligand is 1:0 to 10, more preferably 1:0.01 to 5.

[0019] In another preferred embodiment, the molar ratio of the iron salt / iron complex to the ligand is 1:1 to 3.

[0020] In another preferred embodiment, the molar ratio of the iron salt or iron complex to the chloride-containing additive is 1:0 to 1000, more preferably 1:10 to 50.

[0021] In another preferred embodiment, the iron-based photocatalyst is formed by in-situ complexation of an iron salt and a ligand in the reaction system, wherein the iron salt is selected from the group consisting of FeCl3, FeCl2, and Fe(ClO4)3, and the ligand is a bipyridine ligand.

[0022] In another preferred embodiment, the solvent is selected from the group consisting of esters, halogenated hydrocarbons, alcohols, nitriles, amides, sulfoxides, water, or combinations thereof.

[0023] In another preferred embodiment, the solvent is selected from one or more of ethyl acetate, hexafluoroisopropanol, acetonitrile, and water; preferably acetonitrile.

[0024] In another preferred embodiment, the chloride ion source is selected from the group consisting of quaternary ammonium salts such as lithium chloride, ammonium chloride, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, and tetrabutylammonium chloride, as well as solids or corresponding aqueous solutions such as concentrated hydrochloric acid and pyridine hydrochloride, or combinations thereof.

[0025] In another preferred embodiment, the chloride ion source is a saturated aqueous solution of ammonium chloride.

[0026] In another preferred embodiment, the nitrite is selected from the group consisting of nitrite, sodium nitrite, potassium nitrite, silver nitrite, calcium nitrite, tetrabutylammonium nitrite, sodium hexanonitroscobaltate, sodium cobalt nitrite, potassium cobalt nitrite, or combinations thereof.

[0027] In another preferred embodiment, the nitrite is sodium nitrite and potassium nitrite.

[0028] In another preferred embodiment, the ultraviolet light and / or visible light is generated by an LED light source.

[0029] In another preferred embodiment, the wavelength of the ultraviolet light and / or visible light is 360 nm to 420 nm.

[0030] In another preferred embodiment, the nitration reaction in step (2) is carried out at a temperature of 5°C to 80°C.

[0031] In another preferred embodiment, the nitration reaction is carried out at room temperature of 20°C to 30°C.

[0032] In another preferred embodiment, the molar ratio of the deuterated methane to the nitric acid (HNO3) in the nitrifying agent is 1 to 20:1.

[0033] In another preferred embodiment, the molar ratio of the nitrifying agent to the nitrite additive is 1:0 to 0.01.

[0034] In another preferred embodiment, the molar ratio of the nitrifying agent to the nitrite additive is 1:0.0001~0.001.

[0035] In another preferred embodiment, the residence time of the reactants in the flow microchannel reactor is 1 to 180 min.

[0036] In another preferred embodiment, the residence time of the reactants in the flow microchannel reactor is 20 to 100 minutes.

[0037] In another preferred embodiment, the flow microchannel reactor is selected from a glass microchannel reactor module.

[0038] In another preferred embodiment, the glass microchannel reactor is made of borosilicate glass or an equivalent corrosion-resistant, light-transmitting material.

[0039] In another preferred embodiment, the reaction module may be used individually or in series.

[0040] In another preferred embodiment, the reaction module includes a static mixing structure to enhance gas-liquid dispersion and mixing.

[0041] In another preferred embodiment, the reaction process and product composition can be monitored using conventional analytical methods in the art, such as gas chromatography-flame ionization detector (GC-FID) or gas chromatography-mass spectrometry (GC-MS).

[0042] In another preferred embodiment, the method further includes: after the reaction is completed, recovering the unreacted deuterated methane through the tail gas end of an online gas-liquid separator and recycling it.

[0043] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description

[0044] Figure 1 A diagram of a continuous flow microchannel photoreactor device is shown. Detailed Implementation

[0045] Through extensive and in-depth research and numerous experimental screenings, the inventors have developed a method for synthesizing deuterated nitromethane based on continuous flow photocatalysis. This method uses deuterated methane obtained from Fischer-Tropsch synthesis or electrocatalytic reduction of CO2 as raw material. Direct nitration is achieved in a continuous flow microreactor under the combined action of an iron-based photocatalyst and specific wavelength light irradiation. This effectively suppresses side reactions such as over-nitration, achieving high selectivity (over 90%) and high product purity based on deuterated nitromethane content. This method not only enhances the comprehensive utilization value of deuterated resources but also utilizes an iron-based catalytic system that is widely available, low-cost, and environmentally friendly. It avoids the use of highly toxic dimethyl sulfate and traditional high-temperature, high-pressure gas-phase nitration processes. This continuous flow process is safe, reliable, recyclable, and suitable for industrial production. Based on this, the inventors completed this invention.

[0046] Terminology Explanation Preparation method of deuterated nitromethane Most existing processes for preparing deuterated nitromethanes employ an indirect route: first preparing nitromethane, then performing deuteration. However, the synthesis of nitromethanes inherently presents numerous problems: high toxicity of raw materials, severe pollution, high energy consumption, or poor selectivity, making it difficult to meet the requirements of green chemistry. Furthermore, the C–D bonds in deuterated methane molecules are chemically inert, making it difficult to achieve direct and efficient nitration under mild conditions using traditional methods. Simultaneously, the currently employed batch photocatalytic reaction mode also has inherent drawbacks, such as insufficient mass and heat transfer efficiency, low light energy utilization, difficulty in precisely controlling reaction conditions, and high technical risks during scale-up.

[0047] To address the above problems, this invention proposes a method for preparing deuterated nitromethane in a continuous flow microchannel photoreactor, specifically including the following steps: (1) Continuous supply and mixing of raw materials Deuterated methane gas and an organic solution containing nitrating agents, additives, and iron-based photocatalysts (which may contain ligands) are continuously and stably fed into one or more series-connected continuous flow microchannel reactors via independent delivery systems. The static mixing structure within the reactors allows the gas to form a highly dispersed gas-liquid two-phase system in the liquid phase, thereby improving the mass transfer and effective contact area of ​​deuterated methane in the liquid phase.

[0048] (2) Continuous flow photocatalytic nitration reaction The gas-liquid reaction system obtained in step (1) undergoes photocatalytic nitration reaction in a microchannel reactor under ultraviolet light and / or visible light irradiation and preset temperature and pressure conditions to generate deuterated nitromethane. The reaction system can maintain the required pressure through a back pressure regulating device, maintain the required temperature through a constant temperature module, and control the degree of reaction by controlling the residence time.

[0049] (3) Recovery of deuterated methane and product collection and purification The reaction effluent enters an online gas-liquid separator located at the reactor outlet for separation: the gas phase mainly consists of unreacted deuterated methane and a small amount of nitrogen oxides, which can be compressed and recovered for recycling as feed gas; after the reaction liquid is collected, it undergoes subsequent distillation separation and purification to obtain high-purity deuterated nitromethane product.

[0050] Preferably, the partial pressure of deuterated methane is 1 to 50 bar (absolute pressure), more preferably 10 to 20 bar.

[0051] Preferably, the nitrating agent is an aqueous solution of nitric acid, fuming nitric acid, or a nitrification system composed of nitrate and protic acid, more preferably an aqueous solution of nitric acid or fuming nitric acid, and even more preferably an aqueous solution of nitric acid with a mass fraction of 68 wt.%.

[0052] Preferably, the iron-based photocatalyst is an iron salt or iron complex selected from (including but not limited to) the following group: ferric chloride FeCl3, ferric bromide FeBr3, ferric trifluoromethanesulfonate Fe(OTf)3, ferric trifluoroacetate Fe(TFA)3, ferric sulfate Fe2(SO4)3, ferric nitrate Fe(NO3)3, ferric phosphate FePO4, ferric tetrafluoroborate Fe(BF4)3, ferric perchlorate Fe(ClO4)3, ferric oxalate Fe2(C2O4)3, ferric acetylacetone Fe(acac)3, ferric p-toluenesulfonate Fe(OTs)3, ferric ethylenediaminetetraacetate, and corresponding ferrous salts (FeCl2, FeBr2, FeSO4, etc.) and their anhydrous / hydrated forms or corresponding iron complexes, or combinations thereof.

[0053] Preferably, the iron-based photocatalyst is selected from the group consisting of FeCl3, FeCl2, Fe(ClO4)3, Fe(NO3)3, Fe(BF4)3, or combinations thereof.

[0054] Preferably, the iron-based photocatalyst further includes a ligand, and the ligand may be selected from the group consisting of pyridines, bipyridines, terpyridines, tetrapyridines, phenanthrolines, Py-Boxes, tetraphenylporphyrins and their derivatives, or combinations thereof, preferably bipyridine ligands. The iron-based photocatalyst may be pre-synthesized and then added, or it may be formed by the in-situ complexation of iron salts and ligands in the reaction system.

[0055] Preferably, the iron-based photocatalyst is formed by in-situ complexation of an iron salt and a ligand in the reaction system, wherein the iron salt is selected from the group consisting of FeCl3, FeCl2, Fe(ClO4)3, Fe(NO3)3, and Fe(BF4)3, and the ligand is selected from the group consisting of pyridines, bipyridines, terpyridines, tetrapyridines, phenanthrolines, Py-Boxes, tetraphenylporphyrins and their derivatives, or combinations thereof.

[0056] Preferably, the iron-based photocatalyst is formed by in-situ complexation of iron salt and ligand in the reaction system, and the iron salt is selected from the group consisting of FeCl3, FeCl2, and Fe(ClO4)3, and the ligand is a bipyridine ligand.

[0057] Preferably, the solvent is selected from esters, halogenated hydrocarbons, alcohols, nitriles, amides, sulfoxides, water, or mixtures thereof. More preferably, the solvent is selected from one or more of ethyl acetate, hexafluoroisopropanol, acetonitrile, and water; even more preferably, acetonitrile.

[0058] Preferably, the additive includes a chloride ion source and / or nitrite.

[0059] Preferably, the chloride ion source is selected from the group consisting of quaternary ammonium salts such as lithium chloride, ammonium chloride, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, and tetrabutylammonium chloride, as well as solids or corresponding aqueous solutions such as concentrated hydrochloric acid and pyridine hydrochloride, or combinations thereof, and more preferably a saturated aqueous solution of ammonium chloride.

[0060] Preferably, the nitrite additive is selected from the group consisting of nitrite, sodium nitrite, potassium nitrite, silver nitrite, calcium nitrite, tetrabutylammonium nitrite, sodium hexanotopcobaltate, sodium cobalt nitrite, potassium cobalt nitrite, or combinations thereof, preferably sodium nitrite and potassium nitrite.

[0061] Preferably, the light source is ultraviolet light and / or visible light with a wavelength of 300 nm to 780 nm, and more preferably, the light source is an LED light source with a wavelength of 360 nm to 420 nm.

[0062] Preferably, the reaction is carried out at a temperature of 5°C to 80°C, and more preferably at a room temperature of 20°C to 30°C.

[0063] Preferably, the molar ratio of the deuterated methane to the nitric acid (HNO3) in the nitrifying reagent is 1~20:1.

[0064] Preferably, the molar ratio of the iron salt / iron complex to the ligand is 1:0~10, more preferably 1:1~3.

[0065] Preferably, the molar ratio of the iron salt or iron complex to the chloride-containing additive is 1:0 to 1000, and more preferably 1:10 to 50.

[0066] Preferably, the molar ratio of the nitrifying agent to the nitrite additive is 1:0~0.1, more preferably 1:0.0001~0.01.

[0067] Preferably, the residence time of the reactants in the flow microchannel reactor is 1 to 180 min, more preferably 20 to 100 min.

[0068] Preferably, the flow microchannel reactor is a glass microchannel reactor module (high borosilicate glass or equivalent corrosion-resistant, light-transmitting material), which can be used individually or in series; it may include a static mixing structure to enhance gas-liquid dispersion and mixing.

[0069] Preferably, the reaction process and product composition can be monitored using conventional analytical methods in the art, such as gas chromatography-flame ionization detector (GC-FID) or gas chromatography-mass spectrometry (GC-MS).

[0070] The reagents and raw materials used in this invention are all commercially available.

[0071] Compared with the prior art, the beneficial effects of the present invention are as follows: 1) High-value utilization of resources: Provide high-value-added conversion pathways for deuterated methane obtained in processes such as Fischer-Tropsch synthesis and electrocatalytic reduction of CO2, and enhance the comprehensive utilization value of deuterated resources.

[0072] 2) Activation of C–D bonds under mild conditions: Through the combined action of iron-based photocatalysis and specific wavelength light irradiation, direct nitration is achieved under enhanced mass transfer conditions in a continuous flow microreactor, with significantly lower temperature and pressure conditions than the traditional gas-phase nitration method.

[0073] 3) High selectivity and process controllability: Continuous flow operation ensures the uniformity and controllability of concentration, light dose, temperature, and residence time, which is beneficial for suppressing side reactions such as over-nitration. Under optimal conditions (such as in Example 1), high selectivity of deuterated nitromethane relative to the byproduct deuterated methyl nitrate can be achieved (CN / CO peak area ratio can reach 11:1, corresponding to a deuterated nitromethane selectivity >90%), and the catalyst turnover number (TON) is as high as 591, significantly better than the control experiment without catalyst, ligand, or additives. Simultaneously, the continuous flow process can achieve a comprehensive utilization rate of over 85% for deuterated methane.

[0074] 4) Greening and safety enhancement at the source: Avoid the use of highly toxic dimethyl sulfate and traditional high-temperature and high-pressure gas-phase nitration processes. The continuous flow system has a small liquid holdup, easy heat control, and high inherent safety.

[0075] 5) Catalysts are inexpensive and readily available: Iron-based catalytic systems are widely available, low in cost, environmentally friendly, and have the potential for recycling.

[0076] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Percentages and parts are by weight unless otherwise stated.

[0077] Example 1: Preparation of deuterated nitromethane Preparation of the reaction solution: In a 250 mL reagent bottle, add anhydrous ferric chloride (FeCl3, 8.0 mg, 0.05 mmol), 4,4'-dichloro-2,2'-bipyridine (22.5 mg, 0.10 mmol), saturated ammonium chloride aqueous solution (120 μL, 0.6 mmol, 5 M), sodium nitrite (3.4 mg, 0.05 mmol), and 68 wt.% nitric acid aqueous solution (4.5 mL). Add acetonitrile to a total volume of 150 mL and mix thoroughly to obtain a homogeneous reaction solution. The concentration of nitric acid is approximately 0.5 mol / L (calculated as HNO3).

[0078] System preparation and reaction operation: A glass microchannel reactor module was used (one or more modules can be connected in series; in this embodiment, multiple modules are connected in series, with a total volume of 42 mL). A 400 nm LED array light source and its supporting cooling system were turned on, and the reactor jacket temperature was set to 25 °C, and the back pressure valve was set to 15 bar. First, pure acetonitrile was pumped into the system at a flow rate of 0.25 mL / min for rinsing and wetting. Then, the deuterated methane cylinder was opened, and the flow rate of deuterated methane was controlled at 15 mL / min (standard conditions) using a mass flow controller. After the system pressure stabilized, the injection line was switched to the above reaction solution, and the reaction solution was continuously pumped into the reactor at 0.25 mL / min. A continuous flow photocatalytic nitration reaction was carried out under illumination at 25 °C and 15 bar. Based on the feed, the molar ratio of deuterated methane to nitric acid (calculated as HNO3) was approximately 5.3:1. The reaction effluent enters an online gas-liquid separator: the gas phase mainly consists of unreacted deuterated methane, which can be compressed, recovered, and recycled; the liquid phase is the reaction effluent. After the system has been running stably for 30 minutes, product collection begins at the outlet.

[0079] Product processing and analysis: 100 mL of the reaction effluent was continuously collected. A portion of the sample was analyzed using GC-FID with a DB-WAX column. The results showed that the main product was deuterated nitromethane (CD3NO2), and the main byproduct was deuterated methyl nitrate (CD3ONO2), with a peak area ratio (CN / CO selectivity) of approximately 11:1. The collected 100 mL of reaction solution was subjected to atmospheric distillation, and the fraction collected at 98–106 °C yielded 1.26 g (approximately 19.7 mmol) of a colorless, transparent liquid product.

[0080] The calculated yield of deuterated nitromethane is 4.5 g / d, with a conversion rate of approximately 7.4% based on the feed deuterated methane, approximately 39% based on nitric acid, and 591 iron turnovers (TON). The purity of the deuterated nitromethane in the product is ≥98%.

[0081] The residence time is the total retention volume of the reactor divided by the total flow rate of gas and liquid. The specific calculation process is as follows: 42mL÷[0.25 mL / min + (15 mL / min)÷15 bar) ]= 34 min.

[0082] The yield per unit time is the mass of deuterated nitromethane obtained in 100 mL of reaction solution divided by the running time to obtain 100 mL of reaction solution (100 mL ÷ 0.25 mL / min = 400 min). The specific calculation process is as follows: 1.26 g ÷ 400 min = 7.42 mg / min = 4.5 g / d.

[0083] The conversion rate of deuterated methane is the number of moles of deuterated nitromethane obtained in 100 mL of reaction solution divided by the number of moles of deuterated methane added during the reaction run (400 min). The specific calculation process is as follows: (1.26 g ÷ 64 g / mol) ÷ [(15 mL / min × 400 min ÷ 1000) ÷ 22.4 L / mol] = 7.4%.

[0084] The conversion rate of nitric acid is calculated as follows: (1.26 g ÷ 64 g / mol) ÷ [0.5 M × 0.1 L] = 39%.

[0085] The turnover rate of the iron catalyst is the number of moles of deuterated nitromethane obtained in 100 mL of reaction solution divided by the number of moles of iron catalyst added in 100 mL of reaction solution. The specific calculation process is as follows: (1.26 g ÷ 64 g / mol) ÷ [0.05 mmol × (100 mL ÷ 150 mL) ÷ 1000] = 591.

[0086] Example 2: Based on Example 1, the flow rate of deuterated methane was changed from 15 mL / min (standard conditions) to 20 mL / min (standard conditions), while other conditions remained unchanged. The residence time, calculated using the same method, became 26.5 min. The molar ratio of deuterated methane to nitric acid (calculated as HNO3) was approximately 7.1:1 based on the feed. GC-FID showed a CN / CO selectivity of approximately 11:1. After atmospheric distillation, 1.21 g (18.9 mmol) of a colorless, transparent liquid product was obtained. Based on this, the yield per unit time was calculated to be approximately 4.4 g / d; the conversion of deuterated methane was approximately 5.3%; the conversion of nitric acid was approximately 38%; the TON of the iron catalyst was approximately 567; and the purity of deuterated nitromethane in the product was ≥98%.

[0087] Example 3 (without iron salts, control): Based on Example 1, ferric chloride (FeCl3) was not added, while all other conditions remained unchanged.

[0088] GC-FID showed a CN / CO selectivity of approximately 2.3:1. After atmospheric distillation, 0.08 g of product (approximately 1.25 mmol) was obtained. Based on this, the yield per unit time is approximately 0.3 g / d; the conversion of deuterated methane is approximately 0.47%; and the conversion of nitric acid is approximately 2.5%. Since no iron catalyst was added, TON is not applicable.

[0089] Example 4 (without ligand): Based on Example 1, 4,4′-dichloro-2,2′-bipyridine was not added, and all other conditions remained unchanged.

[0090] GC-FID showed a CN / CO selectivity of approximately 6.7:1. After atmospheric distillation, 0.91 g (approximately 14.2 mmol) of product was obtained. Based on this, the yield per unit time is calculated to be approximately 3.3 g / d; the conversion of deuterated methane is approximately 5.3%; the conversion of nitric acid is 28%; the TON of the iron catalyst is approximately 427; and the purity of deuterated nitromethane in the product is ≥98%.

[0091] Example 5 (without adding saturated ammonium chloride solution additive): Based on Example 1, without adding saturated ammonium chloride solution, all other conditions remain unchanged.

[0092] GC-FID showed a CN / CO selectivity of approximately 10:1. After atmospheric distillation, 1.14 g (approximately 17.8 mmol) of product was obtained. Based on this, the yield per unit time is calculated to be approximately 4.1 g / d; the conversion of deuterated methane is approximately 6.7%; the conversion of nitric acid is 36%; the TON of the iron catalyst is approximately 534; and the purity of deuterated nitromethane in the product is ≥98%.

[0093] Example 6 (without sodium nitrite additive): Based on Example 1, sodium nitrite was not added, and all other conditions remained unchanged.

[0094] GC-FID showed a CN / CO selectivity of approximately 9.8:1. After atmospheric distillation, 1.02 g (approximately 15.9 mmol) of product was obtained. Based on this, the yield per unit time is calculated to be approximately 3.7 g / d; the conversion of deuterated methane is approximately 6.0%; the conversion of HNO3 to nitric acid is 32%; the TON of the iron catalyst is approximately 478; and the purity of deuterated nitromethane in the product is ≥98%.

[0095] Example 7 (using recycled deuterated methane): Based on Example 1, the deuterated methane feedstock was replaced with deuterated methane recovered from the tail gas end of an online gas-liquid separator (which is then compressed and recycled), while all other conditions remained unchanged.

[0096] GC-FID showed a CN / CO selectivity of approximately 12:1. After atmospheric distillation, 1.13 g (approximately 17.7 mmol) of product was obtained. Based on this, the yield per unit time is calculated to be approximately 4.1 g / d; the conversion of deuterated methane is approximately 6.6%; the conversion of HNO3 to nitric acid is 35%; the TON of the iron catalyst is approximately 530; and the purity of deuterated nitromethane in the product is ≥98%.

[0097] Therefore, it can be seen that using recovered deuterated methane for the reaction can maintain the original catalytic efficiency and yield. By recovering and recycling unreacted deuterated methane in the tail gas, the comprehensive utilization rate of deuterated methane can reach more than 85%.

[0098] Example 8 (Light-protected control experiment) Based on Example 1, the 400 nm LED array light source and its associated cooling system were not turned on, while all other conditions remained unchanged. GC-FID analysis showed no detection of the target product, deuterated nitromethane.

[0099] Example 9 (Experiment with different wavelengths of light) Based on Example 1, the 460 nm LED array light source and its supporting cooling system were turned on (the light intensity was calibrated to be equivalent to that of the 400 nm light source), while the other conditions remained unchanged.

[0100] GC-FID showed a CN / CO selectivity of approximately 16:1. After atmospheric distillation, 0.97 g (approximately 15.2 mmol) of product was obtained. Based on this, the yield per unit time is calculated to be approximately 3.5 g / d; the conversion rate of deuterated methane is approximately 5.7%; the conversion rate of HNO3 to nitric acid is 30%; the TON of the iron catalyst is approximately 454; and the purity of deuterated nitromethane in the product is ≥98%.

[0101] The data from each embodiment are summarized in Table 1.

[0102] Table 1: Data Summary Table Note 1: Standard Condition 1 refers to the reaction liquid composition and operating conditions of Example 1 (25 ℃, 15 bar, 400 nm LED, liquid 0.25 mL / min, gas 15 mL / min (standard conditions).

[0103] Experimental data show that this method successfully achieves the direct and efficient nitration of deuterated methane through the synergistic effect of photocatalysis and continuous flow process. Light-shielded experiments (Example 8) and catalyst-free systems (Example 3) confirm the crucial necessity of both light and iron-based catalysts—the absence of either leads to complete reaction stagnation or extremely low efficiency. The introduction of ligands (such as bipyridine derivatives) significantly improved reaction selectivity (CN / CO ratio increased from 6.7:1 to 11:1) and nitric acid conversion (28%→39%), while additives such as ammonium chloride and sodium nitrite further optimized reaction performance (Examples 5 and 6). The process conditions exhibited good robustness: the reaction efficiency remained stable when the gas flow rate fluctuated within the range of 15-20 mL / min (Examples 1 and 2); the recycling of deuterated methane (Example 7) not only maintained the original yield but also increased the overall utilization rate of raw materials to over 85%. Furthermore, the wavelength of the light source has a significant impact on the reaction performance (Example 9). The 400 nm illumination phase exhibits better overall efficiency than the 460 nm phase (4.5 g / d vs 3.5 g / d, TON 591 vs 454), highlighting the potential of light wavelength as a key control parameter.

[0104] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A method for synthesizing deuterated nitromethane based on continuous flow photocatalysis technology, characterized in that, The method includes the following steps: (1) Continuous supply and mixing of raw materials: (a) deuterated methane gas and (b) homogeneous reaction liquid are provided, wherein the homogeneous reaction liquid contains nitrating agent, additive, iron-based photocatalyst and solvent; (a) and (b) are continuously fed into a continuous flow microchannel reactor, thereby forming a gas-liquid two-phase reaction system in the liquid phase of the deuterated methane gas. (2) Continuous flow photocatalytic nitration reaction: The gas-liquid two-phase reaction system obtained in step (1) is subjected to photocatalytic nitration reaction in a microchannel reactor under ultraviolet light and / or visible light irradiation to generate reaction effluent containing deuterated nitromethane; (3) Recovery of deuterated methane and collection and purification of products: The reaction effluent obtained in step (2) is separated to obtain a gas phase rich in unreacted deuterated methane and a liquid phase containing deuterated nitromethane. The liquid phase is separated and purified to obtain the deuterated nitromethane product. The nitrating agent is an aqueous solution of nitric acid, fuming nitric acid, or a nitrification system composed of nitrate and protic acid; The iron-based photocatalyst is an iron salt or iron complex selected from the group consisting of: ferric chloride FeCl3, ferric bromide FeBr3, ferric trifluoromethanesulfonate Fe(OTf)3, ferric trifluoroacetate Fe(TFA)3, ferric sulfate Fe2(SO4)3, ferric nitrate Fe(NO3)3, ferric phosphate FePO4, ferric tetrafluoroborate Fe(BF4)3, ferric perchlorate Fe(ClO4)3, ferric oxalate Fe2(C2O4)3, ferric acetylacetone Fe(acac)3, ferric p-toluenesulfonate Fe(OTs)3, ferric ethylenediaminetetraacetic acid, and corresponding ferrous salts and their anhydrous / hydrated forms or corresponding iron complexes, or combinations thereof; The additives include chloride ion sources and / or nitrites; The wavelength of the ultraviolet and / or visible light is 300 nm to 780 nm.

2. The method as described in claim 1, characterized in that, The iron-based photocatalyst further includes ligands, and the ligands are selected from the group consisting of pyridines, bipyridines, terpyridines, tetrapyridines, phenanthrolines, Py-Boxes, tetraphenylporphyrins and their derivatives, or combinations thereof.

3. The method as described in claim 1, characterized in that, The iron-based photocatalyst is formed by the in-situ complexation of an iron salt and a ligand in the reaction system. The iron salt is selected from the group consisting of FeCl3, FeCl2, Fe(ClO4)3, Fe(NO3)3, and Fe(BF4)3. The ligand is selected from the group consisting of pyridines, bipyridines, terpyridines, tetrapyridines, phenanthrolines, Py-Boxes, tetraphenylporphyrins and their derivatives, or combinations thereof.

4. The method as described in claim 2, characterized in that, The molar ratio of the iron salt / iron complex to the ligand is 1:1~3.

5. The method as described in claim 1, characterized in that, The solvent is selected from the group consisting of esters, halogenated hydrocarbons, alcohols, nitriles, amides, sulfoxides, water, or combinations thereof.

6. The method as described in claim 1, characterized in that, The chloride ion source is selected from the following group: quaternary ammonium salts such as lithium chloride, ammonium chloride, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, and tetrabutylammonium chloride, concentrated hydrochloric acid, pyridine hydrochloride, etc., or corresponding aqueous solutions, or combinations thereof.

7. The method as described in claim 1, characterized in that, The nitrite is selected from the group consisting of nitrite, sodium nitrite, potassium nitrite, silver nitrite, calcium nitrite, tetrabutylammonium nitrite, sodium hexanonitroscobaltate, sodium cobalt nitrite, potassium cobalt nitrite, or combinations thereof.

8. The method as described in claim 1, characterized in that, The nitration reaction described in step (2) is carried out at a temperature of 5°C to 80°C.

9. The method as described in claim 1, characterized in that, The molar ratio of the deuterated methane to the nitric acid (HNO3) in the nitrifying reagent is 1~20:

1.

10. The method as described in claim 1, characterized in that, The residence time of the reactants in the flow microchannel reactor is 1 to 180 minutes.

11. The method as described in claim 1, characterized in that, The method further includes: after the reaction is completed, recovering the unreacted deuterated methane through the tail gas end of an online gas-liquid separator and recycling it.

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