A method for photocatalytic preparation of benzylic deuterated chemicals and deuterated chemicals

Abstract

The present invention discloses a method for photocatalytic preparation of benzylic deuterated chemicals and the deuterated chemicals. The method comprises the steps of: an organic compound containing a benzylic C-H bond is mixed with a mixed system of a deuterium source and a photo-sacrificial agent under the catalytic action of a photocatalyst and a light source, and a direct hydrogen-deuterium exchange reaction occurs to obtain the deuterated chemicals. In the present invention, deuterium oxide is used instead of deuterium gas as the deuterium source, and a room-temperature photocatalytic method is adopted to achieve an efficient and mild direct hydrogen-deuterium exchange reaction, which can solve many problems in the existing preparation of deuterated compounds, such as the need to use high-pressure deuterium gas / hydrogen gas, other expensive deuterium sources, and high-temperature environments. In addition, since low-cost heavy water can be directly used as the deuterium source and the reaction conditions are milder, the new method of the present invention can prepare a series of benzylic deuterated organic compounds and can be applied in chemical production, pharmaceutical preparation, isotope labeling, etc.

Description

Technical Field

[0001] The present invention belongs to the field of photocatalytic preparation of chemicals, and in particular relates to a method for preparing benzyl-deuterated chemicals and the deuterated chemicals. Background Art

[0002] Deuterium is an isotope of hydrogen, consisting of one proton, one electron, and one neutron. It has a higher mass than hydrogen, hence its name, heavy hydrogen. In organic chemistry and biochemistry, deuterated organic chemicals play an important role in structural analysis, kinetic studies, biopharmaceuticals, and drug metabolism due to the deuterium isotope effect.

[0003] The traditional synthesis of deuterated organic compounds requires the introduction of deuterium into the target compound through a multi-step synthesis process. This method is cumbersome, has many by-products, and has a low final yield. However, the synthesis of deuterated chemicals by directly performing hydrogen-deuterium exchange on organic compounds has the advantages of simple steps, high target selectivity, and high reaction economy. However, most of these current synthetic pathways require high temperature, high pressure (deuterium / hydrogen), strong acid, and strong base. Therefore, the industrial preparation of deuterated organic chemicals by direct hydrogen-deuterium exchange faces huge challenges. Summary of the Invention

[0004] In view of the above-mentioned problems of the prior art, the object of the present invention is to provide a method for preparing benzylic deuterated chemicals and deuterated chemicals. The present invention uses deuterated water instead of deuterium gas as the deuterium source, adopts room temperature photocatalysis to achieve an efficient and mild direct hydrogen-deuterium exchange reaction. The present invention can solve many problems in the existing preparation of deuterated compounds, such as the need to use high-pressure deuterium gas / hydrogen, other expensive deuterium sources, and high-temperature environments.

[0005] The technical solution of the present invention is:

[0006] The present invention relates to a method for preparing benzylic deuterated chemicals by photocatalysis. An organic compound containing a benzylic C-H bond on a phenyl ring is mixed with a mixed system of a deuterium source and a photo-sacrificial agent under the catalytic action of a photocatalyst and a light source, and a direct hydrogen-deuterium exchange reaction occurs to prepare the deuterated chemical.

[0007] The reaction formula is as follows:

[0008]

[0009] wherein R is a benzyl group having a substituent, and D is a deuterium atom.

[0010] Preferably, the reaction temperature is 10-60°C.

[0011] Preferably, the photocatalyst is a catalyst containing metallic palladium.

[0012] Preferably, the photocatalyst consists of palladium metal and catalyst A, and the catalyst A is selected from any one of organic dye catalysts, inorganic semiconductor catalysts, and organic semiconductor catalysts. In the preparation method of the present invention, the loading of metal Pd particles is achieved by photodeposition at the initial stage of the reaction process, and a photocatalyst, such as C3N4-Pd, is prepared in-situ, thereby photocatalyzing the subsequent direct hydrogen-deuterium exchange reaction.

[0013] Preferably, the light source is light in any wavelength band from 200 to 500 nm.

[0014] Preferably, the deuterium source is at least one of deuterium water, deuterated methanol, deuterated ethanol, and deuterated acetone.

[0015] Preferably, the photo sacrificial agent is at least one of methanol, ethanol, n-propanol, and isopropanol.

[0016] Preferably, the mass ratio of the organic compound containing a benzylic C-H bond to the deuterium source and the photo sacrificial agent is 1:(1 - 100):(1 - 100).

[0017] The present invention also relates to a deuterated chemical product prepared by the above method and having the structure shown in the following formula (1):

[0018]

[0019] Wherein, R1 to R7 are each one of a hydrogen atom, a carbon atom with a substituent, an oxygen atom with a substituent, a nitrogen atom with a substituent, and a sulfur atom with a substituent.

[0020] The beneficial effects of the present invention are as follows:

[0021] (1) The present invention uses mild and inexpensive deuterium water or deuterated solvents to replace deuterium gas, and realizes a high-conversion direct hydrogen-deuterium exchange reaction under visible light. The reaction conditions are milder, solving the problems of using expensive deuterium sources such as deuterium gas and harsh reaction conditions in existing deuteration reaction schemes;

[0022] (2) The reaction site targeted by the present invention is the benzylic hydrogen atom of the organic compound. The main reaction mechanism is that first, the hydroxyl group of the photo sacrificial agent (alcohol) rapidly undergoes hydrogen-deuterium exchange with heavy water. Under light irradiation, the metal Pd particles can extract the active hydrogen / deuterium atoms of the photo sacrificial agent (alcohol) to form hydrogen (deuterium)ated Pd, and then form a complex coordination with the C-H bond at the benzylic position to undergo a direct hydrogen-deuterium exchange reaction, thereby obtaining the target deuterated organic compound;

[0023] (3) The method of the present invention can directly use relatively inert and low-cost aromatic hydrocarbons (such as toluene, etc.) as reaction raw materials, and can achieve a more difficult direct hydrogen-deuterium exchange reaction. The deuterated product obtained has a C-D bond at the benzylic carbon atom. The new method of the present invention can prepare a series of benzylic deuterated organic compounds, which can be applied in chemical production, pharmaceutical preparation, isotope labeling and other aspects. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The present invention will be further described below in conjunction with the drawings and embodiments:

[0025] Figure 1 is the transmission electron microscope picture of the catalyst sample prepared in Example 1;

[0026] Figure 2 are the XRD characterization data of the catalyst samples C3N4-Pd and C3N4 prepared in Example 1;

[0027] Figure 3 is the H-NMR spectrum of the raw material in Example 2;

[0028] Figure 4 is the H-NMR spectrum of the product in Example 2;

[0029] Figure 5 is the C-NMR spectrum of the product in Example 2. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0030] To make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with the specific embodiments and with reference to the drawings. It should be understood that these descriptions are merely exemplary and are not intended to limit the scope of the present invention. In addition, in the following description, the descriptions of well-known structures and technologies are omitted to avoid unnecessarily confusing the concepts of the present invention.

[0031] Example 1: Preparation of the photocatalyst

[0032] Taking the two-dimensional layered C3N4-Pd as an example of the photocatalyst, the preparation method is as follows:

[0033] Weigh 40 g of urea crystals in a crucible, place it in a muffle furnace, and heat it to 600 °C at a heating rate of 2 °C / min and calcine for 2 hours. After the calcination is completed, wait for it to cool naturally, then take it out of the furnace to obtain about 2 g of C3N4 product.

[0034] Weigh 50 mg of the as-prepared C3N4 sample, add 250 μL of a K2PdCl4 solution with a concentration of 2 mg / L, add 0.6 mL of isopropanol and 1.35 mL of deionized water. Then place the reaction flask into a light-transmitting reaction kettle, replace the reaction system with an argon protection state, and react under 410 nm LED light irradiation for 2 hours. After the reaction is completed, turn off the light source, take out the reaction flask, centrifuge the reaction mixture, remove the supernatant, and then wash and centrifuge the catalyst solid with isopropanol three times to obtain a two-dimensional layered C3N4-Pd catalyst solid sample.

[0035] The characterization of the catalyst prepared in this example is shown in Figures 1 to 2 as follows. Figure 1 Figure (a) is the transmission electron microscopy (TEM) image of the catalyst sample, Figure 2 and Figure (b) is the X-ray diffraction (XRD) data of the catalyst sample and C3N4. Figure 1 The TEM image of Figure (a) shows that the palladium metal particles are successfully and uniformly loaded on the carbon nitride C3N4 support, and the Pd particle size is about 3 - 5 nm; Figure 2 The XRD pattern of Figure (b) only shows the characteristic diffraction signals of carbon nitride C3N4, indicating that the size of the metal Pd particles is very small and cannot be detected by XRD, which is also consistent with the Figure 1 TEM results of Figure (a).

[0036] Example 2: Preparation of diphenylmethane-d2

[0037] Weigh 50 mg of C3N4 into a reaction flask, add 0.1 mmol of diphenylmethane, 0.6 mL of isopropanol, 1.35 mL of deuterated water, and 250 μL of a deuterated K2PdCl4 aqueous solution with a concentration of 2 mg / L. Then ultrasonically oscillate the reaction flask for 2 minutes to mix evenly. Then place the reaction flask into a light-transmitting reaction kettle, replace the reaction system with an argon protection state, turn on the 410 nm LED light source, and irradiate for 10 hours. After the reaction is completed, turn off the light source, centrifuge and separate the reaction mixture, pour out the upper clear liquid, extract the catalyst solid with 1 mL of acetone, filter off the catalyst, and evaporate the solvent. The target product can be obtained without further purification.

[0038] The structure of the obtained product was determined by tests such as H-NMR, C-NMR, and GC-MS. The deuteration rate was calculated by the integration of H-NMR. Figure 3 Figure (c) is the H-NMR spectrum of the raw material, Figure 4 Figure (d) is the H-NMR spectrum of the product, Figure 5 and Figure (e) is the C-NMR spectrum of the product. Comparing the raw material ( Figure 3 ) and the product ( Figure 4) From the H-NMR spectrum, it can be seen that the integral area of the signal of the benzylic hydrogen atoms (chemical shift at 4.0 ppm) of diphenylmethane after the reaction decreased to 0.1, while the integral area of the unreacted raw material at this position should be 2, indicating a deuteration rate of 95%. And the chemical shifts of all hydrogen atoms are the same as those of the raw material, indicating that only the hydrogen-deuterium exchange reaction occurred, and the product on the right side in formula (2) was obtained. Figure 5 The C-NMR spectrum of the product further corroborates that no other side reactions (such as addition reactions, etc.) occurred to the raw material, and only the benzylic C (at 41 ppm) disappeared due to the substitution of the H atom by a deuterium atom.

[0039] The above reaction formula and the deuteration rate of its corresponding product are shown in the following formula (2):

[0040]

[0041] Example 3: Preparation of toluene-d3

[0042] Weigh 50 mg of C3N4 into a reaction flask, add 0.1 mmol of toluene, 0.6 mL of isopropanol, 1.35 mL of deuterated water, and 250 μL of a deuterated aqueous solution of K2PdCl4 with a concentration of 2 mg / L. Then ultrasonically oscillate the reaction flask for 2 minutes to mix it evenly. Then place the reaction flask into a light-transmitting reaction kettle, replace the reaction system with an argon protection state, turn on the 410 nm LED light source, and irradiate for 10 hours. After the reaction is completed, turn off the light source, extract with dichloromethane, and take 0.5 mL of the organic phase for analysis. The deuteration rate of the product can be determined by H-NMR and GC-MS. The above reaction formula and the yield of its corresponding product are shown in the following formula (3):

[0043]

[0044] It should be understood that the above specific embodiments of the present invention are only used for exemplary illustration or explanation of the principle of the present invention, and do not constitute a limitation to the present invention. Therefore, any modifications, equivalent replacements, improvements, etc. made without departing from the spirit and scope of the present invention shall be included within the protection scope of the present invention. In addition, the appended claims of the present invention are intended to cover all changes and modification examples falling within the scope and boundaries of the appended claims, or equivalent forms of such scope and boundaries.

Claims

1. A method for preparing benzylic deuterated chemicals by photocatalysis, characterized in that, An organic compound containing a benzylic C-H bond in the benzene ring is mixed with a mixed system of a deuterium source and a photo-sacrificial agent under the catalysis of a photocatalyst and a light source to undergo a direct hydrogen-deuterium exchange reaction to obtain a deuterated chemical; Among them, the photocatalyst is composed of metallic palladium and C3N4, the deuterium source is at least one of deuterium water, deuterated methanol, deuterated ethanol, and deuterated acetone, and the photo-sacrificial agent is at least one of methanol, ethanol, n-propanol, and isopropanol.

2. The method according to claim 1, characterized in that, The reaction temperature is 10 to 60 °C.

3. The method according to claim 1, wherein The light source is light in any wavelength band from 200 to 500 nm.

4. The method according to claim 1, wherein The mass ratio of the organic compound containing a benzylic C-H bond in the benzene ring to the deuterium source and the photo-sacrificial agent is 1:(1 - 100):(1 - 100).

Images