A preparation method of dichloromethane-d2

Abstract

The present invention discloses a method for preparing dichloromethane-d2, comprising the following steps: performing an electrolytic reaction in an electrolytic cell using chloroform-d1 as a raw material and heavy water as a deuterium source in the presence of an electrolyte; and then reducing the chloroform-d1 at the cathode of the electrolytic cell to produce dichloromethane-d2. The present invention does not require the use of expensive catalysts or reaction raw materials, utilizes inexpensive and readily available raw materials, has simple steps, mild reaction conditions, low costs, high product yield and high degree of deuteration, and is suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of deuterated compound production, in particular to a method for preparing dichloromethane (D2). Background Art

[0002] Dichloromethane-d2 can be used as a solvent for inorganic and organic compounds in chemical reactions. Many compounds have a higher solubility in dichloromethane-d2 than in chloroform-d1. Therefore, dichloromethane-d2 also has important applications as a solvent in NMR spectroscopy.

[0003] In the prior art, the synthesis process for dichloromethane-d2 includes the following:

[0004] Patent US3666821A discloses the deuteration of dichloromethane using heavy water as a deuterium source in the presence of a catalyst (sodium deuteride) and a solvent (dimethyl sulfoxide). Specifically, after the reactants are mixed and heated under reflux for 24 hours, the dichloromethane-d2 is collected and tested to determine its deuteration degree of 33%. After a second round of reflux for 48 hours, the deuteration degree reaches 42%. Therefore, in order to prepare dichloromethane-d2 with a deuteration degree of more than 99%, multiple rounds of iterations are required under high temperature conditions, which consumes a lot of energy and is time-consuming. In addition, the above method requires the use of high-purity sodium deuteride, which is more expensive.

[0005] Patent EP0246805B1 discloses contacting dichloromethane with an aqueous phase containing heavy water and a base (sodium deuteride) in the presence of a phase transfer catalyst to produce dichloromethane-d2. The phase transfer catalysts, including methyltrioctylammonium chloride and tetrabutylammonium bromide, can promote the hydrogen-deuterium exchange reaction. However, this method also requires the use of high-purity sodium deuteride, and the high concentration of base used in this method places higher corrosion resistance requirements on the materials used in the reaction equipment.

[0006] In addition, some methods for preparing dichloromethane-d2 have been reported in domestic and foreign literature. For example, Myers et al. (J. Chem. Phys. 1952, 20, 1420-1427) obtained dichloromethane-d2 by selectively reducing chloroform-d1 in the presence of metallic zinc and acetic acid-d1. However, this method has a low yield and easily produces a large amount of zinc-containing byproducts, which are difficult to separate and purify. In addition, the use of acetic acid-d1 as a deuterium source in this method is more expensive, which is not conducive to industrial scale-up production. Bannard et al. (Can. J. Chem. 1953, 351-356) prepared dichloromethane-d2 by reacting phosphorus pentachloride with formaldehyde-d2. The formaldehyde-d2 in this method is relatively expensive.

[0007] Deuterated dichloromethane has many advantages, but its high price greatly limits its application range. Therefore, it is of great significance to develop an efficient method for preparing dichloromethane-d2. Summary of the Invention

[0008] The object of the present invention is to provide a method for preparing dichloromethane-d2, which has the advantages of mild reaction conditions, low cost, high yield and deuteration degree, and is suitable for industrial production.

[0009] The technical solution adopted by the present invention to solve its technical problem is:

[0010] A method for preparing dichloromethane-d2 comprises the following steps:

[0011] An electrolytic reaction is carried out in an electrolytic cell using chloroform-d1 as a raw material and heavy water as a deuterium source in the presence of an electrolyte. The chloroform-d1 undergoes a reduction reaction at the cathode of the electrolytic cell to produce dichloromethane-d2. The raw material chloroform-d1 has a deuterium substitution degree greater than 99.8%, and the deuterium substitution degree of the heavy water is greater than 99.8%.

[0012] The electrolyte is selected from at least one of tetrabutylammonium fluoroborate, tetrabutylammonium perchlorate, tetrabutylammonium iodide, tetrabutylammonium chloride, and potassium chloride.

[0013] The amount of electrolyte added is 0.1-1.0 mol per 1L of heavy water.

[0014] The volume ratio of chloroform-d1: heavy water = 1:1-1.5.

[0015] The material of the cathode in the electrolytic cell is at least one of Zn, Pb, Sn, Pt, Al, Fe, and Ni.

[0016] The material of the anode in the electrolytic cell is one of platinum, graphite, carbon cloth, RVC, and stainless steel.

[0017] The electrolysis reaction conditions are: direct current electrolysis, electrolysis voltage of 2.8-3.2V, current density of 1-20A / dm 2 , the cathode potential is -0.1 to -2.0 V, and the reaction temperature is controlled at 10-40°C. During the electrolysis reaction of the present invention, the cathode potential relative to the Ag / AgCl (2.5M KCl) reference electrode is -0.1 to -2.0 V, preferably -0.5 to -0.8 V; the current density is preferably 7 to 8 A / dm 2 .

[0018] The process also includes a dichloromethane-d2 separation step: After the reaction is completed, the cathode product of the electrolytic cell is allowed to stand and separate into layers. The lower layer is removed and subjected to distillation to obtain purified dichloromethane-d2. The lower layer is the crude dichloromethane-d2. Conventional distillation of the lower layer can produce nuclear magnetic grade dichloromethane-d2 (purity >99.99%, deuteration >99.5%).

[0019] The method further comprises an anode product treatment step: passing the anode product of the electrolytic cell into a saturated sodium hydroxide aqueous solution for absorption treatment. The anode product is chlorine, which is directly passed into the saturated sodium hydroxide aqueous solution for absorption treatment.

[0020] The electrolytic cell is a diaphragmless electrolytic cell. The electrolysis reaction of the present invention can be carried out intermittently or in a continuous or semi-continuous manner. The electrolytic cell can be a diaphragmless DC stirred tank containing electrodes or a flow DC electrolytic cell of any conventional design.

[0021] The design concept of this technology is based on the fact that chloroform-d1 is a commonly used deuterated solvent with high production and usage, and is relatively inexpensive compared to other deuterated reagents. Under electrochemical reduction conditions, heavy water molecules or deuterium ions gain electrons on the electrode surface and are converted into deuterium atoms. The adsorbed deuterium atoms then undergo a reduction reaction with chloroform-d1 adsorbed on the electrode surface, producing the deuterated product, dichloromethane-d2.

[0022] Cathodic dechlorination reaction

[0023] D2O→D + +OD -

[0024] D + +e - →[D]

[0025] CDCl3+[D]+e - →CD2Cl2+Cl -

[0026] Anodic chlorine evolution reaction

[0027] 2Cl - →Cl2+2e - .

[0028] Based on the above design ideas, the present invention provides a method for preparing deuterated dichloromethane by dechlorination of deuterated chloroform as shown in formula (I).

[0029] CDCl3+D2O→CD2Cl2 (I).

[0030] The present invention uses an electrolytic cell as a reactor to electrolyze the raw material; chloroform-d1 undergoes a reduction reaction at the cathode of the electrolytic cell to produce dichloromethane-d2. The progress of the electrolytic reaction is monitored by conventional methods in the art, including GC, 1 HNMR and 2 The reaction was monitored by H NMR, and the disappearance of chloroform-d1 was generally regarded as the end point of the reaction.

[0031] The beneficial effects of the present invention are: the present invention does not require the use of expensive catalysts or reaction raw materials, the raw materials are cheap and easily available, the steps are simple, the reaction conditions are mild, the cost is low, the product yield and deuteration degree are high, and it is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is the NMR detection image of the product. DETAILED DESCRIPTION

[0033] The technical solution of the present invention is further described in detail below through specific embodiments.

[0034] In the present invention, unless otherwise specified, the raw materials and equipment used can be purchased from the market or are commonly used in the art. The methods in the following examples, unless otherwise specified, are all conventional methods in the art.

[0035] Example 1

[0036] A diaphragmless electrolytic cell was used as the reactor, with a nickel cathode and graphite anode. The distance between the cathode and anode was 0.5 cm. The electrolyte consisted of 10 mL of chloroform-d1 (deuterated > 99.8%) and 10 mL of a 0.5 mol / L nBu4NBF4 deuterated water solution.

[0037] During the electrolysis process, the temperature was controlled at 30°C and the current density was controlled at 10A / dm 2 The electrolysis voltage was 3.0 V, the cathode potential was -0.5 to -0.8 V (reference electrode Ag / AgCl (2.5 M KCl)), and the electrolysis was stopped after reacting at room temperature for 12 hours.

[0038] After separating the electrolyte, the lower organic layer was dried over anhydrous sodium sulfate and filtered to obtain a colorless liquid. The target product, dichloromethane-d2, was obtained by simple distillation and collection of the 45°C fraction. 1 H NMR (400 MHz) δ 5.33 (CD2Cl2), 1.53 (water peak), see Figure 1 .

[0039] In this embodiment, the yield of dichloromethane-d2 is 91%, the purity is >99%, and the deuteration degree is 99.61%.

[0040] Yield detection: The calculation formula is: actual weight of dichloromethane-d2 / theoretical weight of dichloromethane-d2*100%.

[0041] Purity detection: gas chromatography is used for detection.

[0042] Deuterium substitution detection: The deuterium substitution degree was detected by nuclear magnetic resonance hydrogen spectroscopy, and quantified by capillary internal standard method.

[0043] Examples 2-5

[0044] The preparation method of this embodiment is the same as that of Example 1, except for the choice of anode material. Specifically, Example 2 uses platinum as the anode material; Example 3 uses carbon cloth as the anode material; Example 4 uses RVC as the anode material; and Example 5 uses stainless steel as the anode material. See Table 1 for details.

[0045] Examples 6-11

[0046] The preparation method of this example is the same as that of Example 1, except for the choice of cathode material. Specifically, Example 6 uses zinc as the cathode material; Example 7 uses lead as the cathode material; Example 8 uses tin as the cathode material; Example 9 uses platinum as the cathode material; Example 10 uses aluminum as the cathode material; and Example 11 uses iron as the cathode material. See Table 1 for details.

[0047] Examples 12-17

[0048] The preparation method of this example is the same as that of Example 1, except for the choice of electrolyte. Specifically, Example 12 uses tetrabutylammonium perchlorate as the electrolyte; Example 13 uses tetrabutylammonium iodide as the electrolyte; Example 14 uses tetrabutylammonium chloride as the electrolyte; Example 15 uses tetrabutylammonium dihydrogen phosphate as the electrolyte; Example 16 uses potassium chloride as the electrolyte; and Example 17 does not add an electrolyte. See Table 1 for details.

[0049] Examples 18-23

[0050] The preparation method of this embodiment is the same as that of embodiment 1, except for the control of reaction conditions. Specifically, the reaction temperature of embodiment 18 is 10°C; the reaction temperature of embodiment 19 is 40°C; the electrolysis voltage of embodiment 20 is 2.8V, and the cathode current density is 1A / dm 2 The electrolysis voltage of Example 21 is 3.2V, and the cathode current density is 20A / dm 2 ; The cathode potential of Example 22 is -0.1 to -0.3V; the cathode potential of Example 23 is -1.8 to -2.0V.

[0051] Table 1 Reaction conditions and test data of Examples 1-23

[0052]

[0053]

[0054] Example 24

[0055] The preparation method of this example is the same as that of Example 1, except that 10 mL of chloroform-d1 (deuterated >99.8%) and 15 mL of 0.1 mol / L nBu4NBF4 deuterated water solution are used as the electrolyte. The yield of dichloromethane-d2 is 91%, the purity is 94%, and the deuterated degree is 99.5%.

[0056] Example 25

[0057] The preparation method of this example is the same as that of Example 1, except that 10 mL of chloroform-d1 (deuterium substitution > 99.8%) and 10 mL of 1 mol / L nBu4NBF4 deuterated water solution are used as the electrolyte. The yield of dichloromethane-d2 is 88%, the purity is 90%, and the deuterium substitution is 99.5%.

[0058] The embodiment described above is only a preferred solution of the present invention and does not limit the present invention in any form. Other variations and modifications are possible without exceeding the technical solution described in the claims.

Claims

1. A method for preparing dichloromethane-d2, characterized in that, The following steps are involved: In an electrolytic cell, an electrolytic reaction is carried out using chloroform-d1 as a raw material and heavy water as a deuterium source in the presence of an electrolyte; chloroform-d1 undergoes a reduction reaction at the cathode of the electrolytic cell to obtain dichloromethane-d2; The material of the cathode in the electrolytic cell is at least one of Zn, Pb, Sn, Pt, Al, Fe, and Ni; The electrolysis reaction conditions are: direct current electrolysis, electrolysis voltage of 2.8-3.2V, current density of 1-20A / dm 2 , the cathode potential is -0.1~-2.0V, and the reaction temperature is controlled at 10-40℃.

2. The preparation method according to claim 1, characterized in that The electrolyte is selected from at least one of tetrabutylammonium fluoroborate, tetrabutylammonium perchlorate, tetrabutylammonium iodide, tetrabutylammonium chloride, and potassium chloride.

3. The preparation method according to claim 1, characterized in that The amount of electrolyte added is 0.1-1.0 mol per 1L of heavy water.

4. The preparation method according to claim 1, 2 or 3, characterized in that: The volume ratio of chloroform-d1: heavy water = 1:1-1.

5.

5. The preparation method according to claim 1, 2 or 3, characterized in that: The material of the anode in the electrolytic cell is one of platinum, graphite, carbon cloth, RVC, and stainless steel.

6. The preparation method according to claim 1, 2 or 3, characterized in that: It also includes a dichloromethane-d2 separation step: after the reaction is completed, the cathode product of the electrolytic cell is allowed to stand and separate into layers, and the lower layer liquid is taken out for distillation to obtain purified dichloromethane-d2.

7. The preparation method according to claim 1, 2 or 3, characterized in that: The method also includes an anode product treatment step: passing the anode product of the electrolytic cell into a saturated sodium hydroxide aqueous solution for absorption treatment.

8. The preparation method according to claim 1, 2 or 3, characterized in that: The electrolytic cell is a diaphragm-free electrolytic cell.

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