CN117903008B - Method for synthesizing oxynitride by using aniline - Google Patents

Abstract

The present invention discloses a method for synthesizing nitrogen oxides from aniline. Using a micro-droplet reaction device, an aqueous solution of an aniline compound of a certain concentration is sprayed. The resulting target product is collected in a round-bottom flask and separated to obtain nitrogen oxides. This method solves the problem of harsh reaction conditions and the need for catalysts in the prior art of preparing nitrogen oxides from aromatic amines. Furthermore, the method is green, mild, catalyst-free, rapid, and has a high yield.

Description

Method for synthesizing oxynitride by using aniline

Technical Field

The invention relates to the field of green synthetic chemistry, in particular to a method for synthesizing oxynitride by using aniline.

Background

Small size, high electric field microdroplets have very unique chemical properties, such as being able to accelerate chemical reactions, or to achieve some reactions in the liquid phase that cannot occur. Recently, it has been found that even without applying high pressure, electrochemical cell phenomenon exists on the surface of some micro-droplets, and active species such as electrons, hydroxyl radicals and water radical cations can be generated, and spontaneous oxidation or reduction reaction can be further induced. Because of the ultrahigh electric field at the air-water interface of the droplet reaction, hydroxyl radical and water radical cationic dimer can be formed, and the dimer is easy to decompose to generate active oxygen species such as protonized water and hydroxyl radical, so as to promote continuous initiation of various oxidation reactions in the micro-droplets.

N, N-Dimethylaniline (DMA) is commonly used in medicine as a raw material for synthesizing pharmaceutical intermediates, and can be used for synthesizing vanillin in the aspect of food. At present, researches on the substances mainly focus on quantitative detection, and researches on oxidation reaction and gas phase dissociation reaction mechanisms of the substances are less. The detection of a transient intermediate DMA ^+· with a half-life of less than 1 microsecond using electrochemical mass spectrometry techniques has been reported by the scholars, and the generation of this intermediate results from the electrochemical oxidation process. The task group of novalum explored the C-H/N-H cross-coupling reaction of DMA ^+· with phenoxazine.

Amine N-oxide (R ₃N⁺-O^-) was first described in 1899 by Dunston and Goulding and was named "oxamines". For example, they have synthesized triethylamine oxide of the formula (C ₂H₅)₃ NO) from hydroxylamine and ethyl iodide they have also published a first method of synthesizing amine N-oxide from tertiary amines with hydrogen peroxide Meisenheimer in 1913 and 1919 further experiments were conducted to oxidize amine N-oxide with hydrogen peroxide he described a method of synthesizing N-allyl-N-methylaniline with N-allyl-N-methylaniline and hydrogen peroxide in 60 and 70 th century, and interest in amine oxides has increased due to the discovery that some compounds can be used as detergents and foam stabilizers.

Disclosure of Invention

The invention aims to at least solve one of the technical problems in the prior art, and provides a novel reaction for forming micro-droplets by spraying an aniline compound aqueous solution into micro-droplets to quickly synthesize nitrogen oxides, wherein the reaction is quick in atomic economy, green, pollution-free and free of catalyst, and is a model of green synthetic chemistry.

N, N-dimethylaniline is used as a raw material of a drug synthesis intermediate, has great application potential in synthesis, utilizes the high electric field effect of micro-droplets as a synthesis trigger, utilizes the gas source of a metal pipe to blow off the reaction liquid at the capillary orifice to form small droplets with high electric field, and utilizes the characteristics of the micro-droplets to generate free radical reaction to form the N, N-dimethylaniline oxynitride with m/z of 138.

A method for synthesizing oxynitride by using aniline adopts a micro-droplet reaction device, so that aniline compound aqueous solution is blown off to form micro-spray under the drive of carrier gas flow, solute aniline compound can form aniline compound free radical in spray, solvent water can form hydroxyl free radical, and aniline compound free radical and hydroxyl free radical act to generate oxynitride.

Preferably, the aniline compound comprises at least one of N, N-dimethylaniline, N-dimethyl-m-hydroxyaniline, N-diethylaniline, N-dimethyl-p-methoxyaniline, N-dimethyl-p-chloroaniline, N-dimethyl-p-bromoaniline and N, N-dimethyl-p-methylaniline.

Taking N, N-dimethylaniline as an example, the reaction principle is as follows:

Preferably, the carrier gas is air and/or an inert gas.

Preferably, the concentration of the aqueous solution of the aniline compound is 10-1000ppm.

Preferably, the flow rate of the carrier gas stream is 0.8-1.0MPa.

Preferably, the micro-droplet reaction device comprises a capillary tube, a metal outer tube and a tee joint, wherein the metal outer tube is sleeved at the outer end of the capillary tube, a cavity formed between the metal outer tube and the capillary tube is used for gas circulation, the cavity is communicated with a gas pipeline, the tee joint is used for connecting the metal outer tube and the gas pipeline, the tee joint is positioned outside the capillary tube, and the front end of the capillary tube is exposed out of an outlet of the metal outer tube by 0.1-0.3mm.

Preferably, the inlet of the capillary tube is connected with a sample injector through a sample injection passage.

Preferably, the capillary is made of quartz glass.

Preferably, the method specifically comprises the following steps:

Preparing aniline compound water solution, making it pass through capillary tube at a certain flow rate, forming micro-liquid drop by means of blowing-off impact of carrier gas, in the interior of micro-liquid drop the intermediate free radical cation and hydroxyl free radical are contained, and making them implement reaction to form oxynitride, adopting isotope deuterium mark and isotope ¹⁸ O mark, and adopting other conditions to retain them, and utilizing correspondent first-stage mass spectrum data and second-stage mass spectrum data analysis to obtain the ion with correspondent additive magnitude, so that it can define the compound product formed from hydroxyl free radical and aniline compound.

The invention has the following beneficial effects:

By adopting the free radical coupling reaction in the micro liquid drops, the invention avoids the traditional tedious and lengthy reaction processes of high temperature and high pressure, acid-soluble alkali dissolution, catalyst and the like, the cost of the spray formed by the invention is low, air can be used as an air source, and the source of the air source is convenient. The whole reaction time is extremely short, a product signal can be obviously seen through mass spectrometry at the moment of forming spray, the free radical coupling reaction can be instantly generated, the reaction can be efficiently generated by regulating and controlling experimental conditions such as air pressure, flow rate, distance and the like, the whole device is simple, the modification cost is low, the online in-situ analysis can be realized, the offline modification of the prepared product can be realized, the product can be generated at the moment of forming the spray, and the whole process is efficient, rapid, green and environment-friendly. The method has no strict requirement on the external conditions of the reaction, can be carried out at normal temperature and normal pressure, uses water as a solvent, has clean products, few byproducts, convenient source of air sources and no pollution. The method provides a new thought for the synthesis reaction of the nitrogen oxides, avoids the defects of large using amount and long reaction time in the prior art, and has great significance for synthesizing the nitrogen oxides. The research utilizes micro-droplet reaction to obtain stable intermediate free radical cations which are difficult to capture in other modes, is helpful to deepen understanding of oxidation reaction characteristics of water droplet chemistry promotion, and is expected to apply the technical method to the fields of chemical industry, pharmacy and the like.

Drawings

The above advantages of the present invention will become apparent and readily appreciated in connection with the following drawings, wherein;

FIG. 1 is a schematic diagram of the apparatus for synthesizing N, N-dimethylaniline nitroxide according to the present invention;

FIG. 2 is a general signal comparison of water radical cations before and after sample injection and a product signal before and after sample injection;

FIG. 3 is a primary and secondary mass spectrum of the free radical cation product (m/z 138) formed by the free radical coupling reaction after spray formation, and the corresponding isotopic label;

FIG. 4 is a graph showing the results of the condition optimization of DMA aqueous solution micro-droplet reaction to generate hydroxylamine compounds, wherein a-d respectively correspond to different condition optimization, and respectively correspond to carrier gas pressure (a), sample outlet-mass spectrometry port distance (b), flow rate (c) and sample concentration (d);

FIG. 5 is a mass spectrum of the reaction of different types of substituted anilines with hydroxyl radicals, wherein a is DMA (N, N-dimethylaniline), b is meta-hydroxy substituted (N, N-dimethyl-m-hydroxyaniline), c is N, N-diethylaniline, d is N, N-dimethyl-p-methoxyaniline, e is N, N-dimethyl-p-chloroaniline, f is N, N-dimethyl-p-bromoaniline, and g is N, N-dimethyl-p-methylaniline.

Detailed Description

For the purposes of promoting an understanding of the principles of the invention, reference will now be made in detail to the embodiments of the invention, examples of which are illustrated in the accompanying drawings. Several reaction examples of the present invention are given in the accompanying drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the examples set forth herein. Rather, these reaction examples are provided to make the disclosure of the present invention more public and transparent.

In this document, unless explicitly stated or limited otherwise, the terms "connected," "affixed," "connected," and the like are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected, mechanically connected, or non-mechanically connected, directly connected, or connected via an intermediary, or internally communicated between elements. The specific meaning of the above terms in the present invention can be understood by those of ordinary skill in the art according to the specific circumstances.

Referring to fig. 1, a schematic structure of an experimental apparatus of the present invention;

The device comprises a capillary tube 2, a metal outer tube 3, a tee joint, an air path 4, a sample injection passage 6 and a mass spectrometer 5.

The capillary tube 2 is sleeved in the metal outer tube 3, protrudes out of the outer tube by 0.2mm approximately, is parallel to the metal outer tube, the position of the capillary tube 2 is fixed through a tee joint, the capillary tube 2 is connected with the sample injection passage 6, and the sample injection passage 6 is connected with the injector 1 in a specific test, and DMA aqueous solution is filled in the injector. The metal outer tube 3 is fixedly connected to the tee joint and sleeved outside the capillary tube 2, a nitrogen source passage is arranged in a space between the metal outer tube 3 and the capillary tube 2, the upper end of the tee joint is fixedly connected with the air inlet passage 4, and the nitrogen source can reach the liquid outlet of the capillary tube 2 from the passage through the tee joint by the metal outer tube 3 to blow off the reaction liquid to form micro liquid drops. The three cervical vertebrae bottle is used for collecting the spray containing the product, and has three necks, the middle is used for fixing the reaction device, the metal outer tube 3 sleeved with the capillary tube 2 is fixed on the middle mouth, the liquid outlets of the metal outer tube 3 and the capillary tube 2 are at a certain distance from the bottle bottom, and the other two mouths are respectively used as an air outlet and a liquid taking mouth, so that the collected solution containing the product can be extracted.

The capillary is a quartz capillary with the diameter of 0.19mm, and the reaction liquid is injected into the capillary from an external injector and passes through the capillary at a certain flow rate, but the method is not limited to the method.

The metal outer tube is a metal middle through tube with the inner diameter of 0.4mm, is sleeved outside the capillary tube, is fixed on the tee joint, and gas passes through the outside of the capillary tube and the metal outer tube at a certain pressure flow rate to reach the front section capillary tube orifice to blow off the reaction liquid to form tiny liquid drops.

Based on the device and the functions of the elements, a method for synthesizing N, N-dimethylaniline comprises the following steps:

The sample is injected into the capillary tube 2 through the sample injection passage 6, the sample is passed through the capillary tube 2, passes through a tee joint, reaches a liquid outlet of the capillary tube 2 through a gas circuit, passes through a metal outer tube 3 through the tee joint, blows off reaction liquid at the tube orifice to form micro-droplets, stable aniline compound free radicals (DMA < + >) and water free radical cations are decomposed into hydroxyl free radicals due to the high electric field characteristic of the micro-droplets, the DMA < + > and the hydroxyl free radicals are subjected to free radical coupling, and N, N-dimethylaniline nitrogen oxides are synthesized, wherein a gas source is mainly nitrogen, and air can be used as a nitrogen source. The product base peak can be detected by the mass spectrometer 5, under the same conditions, the product is collected by using a three-cervical flask, the product peak can be detected on the mass spectrometer 5 by using ESI-MS, and verification shows that the product can be collected by using the three-cervical flask.

In the specific application, the spraying state is related to the air pressure of the air source and the sample injection amount of the reaction liquid, and the spraying state can directly influence the reaction effect. The optimal reaction conditions are found by exploring and optimizing the reaction conditions, wherein the air pressure is 0.9MPA, the sample injection flow is 7 mu L/min, but the method is not limited to the method, the pressure can be 0.8-1.0Mpa, and the sample injection flow is 6-8 mu L/min.

In specific applications, it was also found that the concentration of the reaction solution had a great influence on the efficiency of the coupling reaction, and from 1ppm, 10ppm, 100ppm, 1000ppm of the reaction solution was reacted on line, the product signal of 138 of the reaction solutions of 100ppm and 1000ppm was detected as a basal peak in the mass spectrometer, and the product signal increased with increasing concentration.

The gas stream in the process of the present invention may cause the solvent water to form water radical cations that may decompose to form hydroxyl radicals. The reactants can also form DMA + & free radicals in the microdroplets, which are coupled to form N, N-dimethylanilinium oxides. The spray reaction of the reaction solution with pure water shows that the cation signal of the water radical in the reaction solution is reduced compared with that of pure water, and the generated hydroxyl radical participates in the reaction, so that the signal detected by mass spectrum is reduced.

The hydroxyl free radical in the method comes from a solvent, through verification by using D ₂ O and H ₂ ¹⁸ O, under the condition that other conditions are consistent, the solvent water is changed into deuterated water and heavy oxygen water, signals of 139 and 140 can be obviously enhanced through a mass spectrometer, and the coupling product of the deuterium-labeled hydroxyl free radical and the heavy oxygen-labeled hydroxyl free radical with DMA ^+· can be confirmed through secondary and tertiary analysis.

The invention is further illustrated by the following examples.

The metal outer tube in the following examples was a quartz capillary tube having an inner diameter of 0.4mm and a capillary tube having a diameter of 0.19 mm. The following conditions are not specified as preferable conditions.

Example 1

With the apparatus of FIG. 1, the sample was injected through the injection needle in the injection path, the carrier gas was turned on, and other conditions were the same (the air pressure was 0.9MPA, the injection flow rate was 7. Mu.L/min), and a significant water radical cation (a decrease in H ₂O)²⁺. M/z36 signal and a significant increase in the product signal m/z 138) was observed on the mass spectrometer as compared with the pure water feed, as shown in FIG. 2.

Example 2

With the apparatus shown in FIG. 1, a concentration (1 ppm, 10ppm, 100ppm, 1000 ppm) of aqueous N, N-dimethylaniline solution was fed into the sample injection passage and was blown off by the air supply to form micro droplets, thereby forming DMA+ & and water free cations, both of which can be observed by the mass spectrometer as corresponding ion signals m/z121 and m/z36, and a product peak of a new peak m/z138 added with 17Da was formed, as shown in FIG. 2. At the same time, a trend of decreasing the signal of m/z36 compared with pure water can be observed, and the side surface shows that the water radical cation of m/z36 participates in the action and reacts with the reactant ion of m/z121 to generate the product of synthesizing m/z138 by coupling hydroxyl radical with DMA+. Further, by using isotope deuterium labeling and isotope ¹⁸ O labeling experiments to change the solvent H ₂ O into D ₂ O and H _c ¹⁸ O, and keeping other conditions unchanged, adding 18Da and 19Da product signals respectively, and using corresponding primary and secondary mass spectrum data analysis to determine that the ions with mass number added with 17Da are the products of the actions of OH and DMA+ from the solvent, as shown in FIG. 3, further analyzing the secondary and tertiary mass spectrum data, it can be found that the product [ M+OH ] + & lt is mainly lost 17Da after collision and cleavage, the product [ M+OD ] + & is mainly lost 18Da, and the product [ M+ ^c OH ] is mainly lost 19Da, so that M/z121 fragment ions are obtained, and thus it can be determined that the 17Da with increased mass number is the hydroxyl radical formed from the solvent.

Referring to FIG. 2, FIG. 2 shows a total ion flow diagram (TIC) and a selective ion flow diagram (EIC) obtained by introducing a certain amount of pure water into a sample channel and introducing an aqueous solution of N, N-dimethylaniline after a period of time, and it can be found that m/z36 is rapidly decreased and m/z138, m/z121 and m/z122 are rapidly increased after introducing the aqueous solution of N, N-dimethylaniline. Indicating that m/z36 is reacted to form a new m/z138.

Example 3

The method performance of the device was evaluated using the device shown in fig. 1. Meanwhile, by adopting the same method, the same experimental parameter conditions and the same mass spectrum experimental conditions as in the example 2, N-dimethylaniline aqueous solutions (1 ppm,10ppm,100ppm and 1000 ppm) with different concentrations are sequentially added into the sample injection channel, so that a better linear relation between the different concentrations of the N, N-dimethylaniline aqueous solutions and the m/z138 of the water radical cation coupling product can be obtained (figure 4 d), and when the concentration of the N, N-dimethylaniline aqueous solution is 10ppm, obvious m/z138 ions can be still detected (figure 4). The device was optimized for conditions under which the m/z138 signal intensity was found to be E4 (FIG. 4).

Example 4

The universality of the method was evaluated using the apparatus shown in fig. 1. The same experiment was performed on a series of N, N-dimethylaniline compounds, the structure of which is shown in FIG. 5. By adopting the same method, the same experimental parameter conditions and the same mass spectrum conditions as those of the embodiment 2, N-dimethylaniline compound aqueous solutions with different substituent groups are sequentially added into the sample injection channel, signals (shown in figures 2 and 3) of the actions of various N, N-dimethylaniline compounds and hydroxyl radicals can be obtained, which shows that the N, N-dimethylaniline compound comparative solution and the hydroxyl radicals undergo free radical coupling reaction to generate a 17Da added free radical cation peak, and the device can be suitable for synthesizing corresponding nitrogen oxides by the N, N-dimethylaniline compounds, and is particularly suitable for the drug synthesis research of the compounds.

In summary, by adopting the device and the method for synthesizing the oxynitride, under the condition of no electricity, the reaction liquid is directly blown away by a nitrogen gas source (which can be air) to form micro-droplets, so that the raw material is convenient. The method has the advantages that the air pressure is controlled, the spraying state is regulated, the pure water can generate m/z36 water radical cations to obtain signals, the water radical cations can form hydroxyl radicals, then the pure water is converted into N, N-dimethylaniline aqueous solution, the radical coupling reaction in micro-droplets is carried out under the condition of the previous regulation, N-dimethylaniline nitrogen oxides are generated, the whole device is simple, the object color is pollution-free, the reaction time of forming the hydroxyl radicals by water radical cation clusters and the action of DMA+ is fast, the high-flux analysis can be realized, and the method has important significance for synthesizing the nitrogen oxides of aniline compounds in a gas source.

In the description of the present specification, a description referring to terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

The foregoing examples illustrate only a few embodiments of the invention and are described in detail herein without thereby limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims (7)

1. A method for synthesizing nitrogen oxides from aniline, characterized in that a micro-droplet reaction device is used to disperse an aqueous solution of an aniline compound under the influence of a carrier gas flow to form a micro-spray, wherein the solute aniline compound forms aniline compound free radicals in the spray, and the solvent water forms hydroxyl radicals, and the aniline compound free radicals and the hydroxyl radicals react to form nitrogen oxides; The aniline compound includes at least one of N,N-dimethylaniline, N,N-dimethyl-m-hydroxyaniline, N,N-diethylaniline, N,N-dimethyl-p-methoxyaniline, N,N-dimethyl-p-chloroaniline, N,N-dimethyl-p-bromoaniline, and N,N-dimethyl-p-methylaniline; The micro-droplet reaction device includes a capillary, a metal outer tube and a tee. The metal outer tube is sleeved on the outer end of the capillary. The cavity formed between the metal outer tube and the capillary is used for gas circulation. The cavity is connected to the gas pipeline. The tee interface is used to connect the metal outer tube and the gas pipeline. It is located outside the capillary, and the front end of the capillary is exposed 0.1-0.3 mm from the outlet of the metal outer tube. 2. The method for synthesizing nitrogen oxides using aniline according to claim 1, wherein the carrier gas is air and/or an inert gas. 3. The method for synthesizing nitrogen oxides using aniline according to claim 1, wherein the concentration of the aniline compound aqueous solution is 10-1000 ppm. 4. The method for synthesizing nitrogen oxides from aniline according to claim 1, wherein the flow rate of the carrier gas is 0.8-1.0 MPa, and/or the injection flow rate is 6-8 μL/min. 5 . The method for synthesizing nitrogen oxides using aniline according to claim 1 , wherein the inlet of the capillary is connected to a sample injector through a sample injection passage. 6. The method for synthesizing nitrogen oxides using aniline according to claim 1, wherein the capillary is made of quartz glass. 7. The method for synthesizing nitrogen oxides using aniline according to claim 1, characterized in that it specifically comprises the following steps: An aqueous solution of aniline compounds was prepared and passed through a capillary at a certain flow rate. When reaching the capillary outlet, it was blown away by the carrier gas to form microdroplets. The microdroplets contained intermediate free radical cations and hydroxyl radicals, which reacted to form nitrogen oxides. Deuterium isotope labeling and ¹⁸ O isotope labeling were used, and other conditions remained unchanged. The corresponding primary and secondary mass spectrometry data were analyzed to show the presence of ions of corresponding order of magnitude, which can be determined to be the composite product formed by the reaction of hydroxyl radicals and aniline compound radicals.