Synthetic method of deuterated dichloromethane

Abstract

The invention discloses a synthetic method of deuterated dichloromethane, and belongs to the technical field of organic synthesis. The invention provides a synthetic method of deuterated dichloromethane, which comprises the following steps: mixing deuterated chloroform, an active deuterium substrate, a deuterated phosphine oxide compound, a cationic organic small molecule catalyst and alkali for reaction, and after the reaction, performing post-treatment to obtain the deuterated dichloromethane. According to the invention, deuterated chloroform is taken as a main raw material, and deuterated dichloromethane can be obtained through smooth reaction in a deuterated phosphine oxide compound, an active deuterium substrate, alkali and a cationic organic small molecule catalyst. The reaction strategy is carried out under mild reaction conditions, and byproducts can be directly sold as products or recycled, so that the influence on the environment is greatly reduced, and the preparation cost of the products is effectively reduced.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing deuterated dichloromethane. Background Technology

[0002] Deuterated dichloromethane is a common organic compound with the chemical formula CD₂Cl₂, which is a colorless liquid at room temperature. This type of compound has wide applications in scientific research and industrial production, and has high economic value; therefore, developing efficient and low-cost synthetic methods is of great significance.

[0003] The most convenient synthesis of deuterated dichloromethane can be achieved through the hydrogen-deuterium exchange reaction of dichloromethane. However, dichloromethane can only produce about 33% deuterated dichloromethane through a simple hydrogen-deuterium exchange reaction, and even with further enrichment, only 42% of the deuterated product can be obtained. The literature Chem. Abstr. 1970, 72, II0766y and J. Chem. Phys. 1952, 20, 1420 established a method for the direct reaction of CH3CO2D with deuterated chloroform to produce deuterated dichloromethane, but this method has low yield and loses a large number of deuterium atoms, resulting in high cost. Leitch et al. (Can. J. Chem. 1953, 351) also obtained deuterated dichloromethane using the reaction of CD2O and PCl5, but the cost remained high. Interestingly, EP0246805A1 further developed a synthetic method for preparing deuterated dichloromethane via a hydrogen-deuterium exchange reaction. In CN118388312A, dichloromethane was successfully converted to deuterated dichloromethane under the action of a phase transfer catalyst, with a deuterium content as high as 99% in the product. Recently, it has also been reported that carbon tetrachloride can be converted to deuterated dichloromethane using a heterogeneous catalyst, with a conversion rate of about 60% and a purity of over 99%.

[0004] Although the synthesis methods of deuterated dichloromethane have been thoroughly studied, the production cost of deuterated dichloromethane remains high due to the waste of deuterium atoms and the added costs of other reactants. Summary of the Invention

[0005] This invention addresses the problems of low conversion rate and high cost in existing methods for preparing deuterated dichloromethane by developing a new synthetic method for deuterated dichloromethane. This method utilizes deuterated chloroform to generate deuterated dichloromethane with the molecular formula CD2Cl2.

[0006] This invention provides a method for synthesizing deuterated dichloromethane, comprising the following steps: adding deuterated chloroform, an active deuterated substrate, a deuterated phosphine oxide compound, a cationic small organic molecule catalyst and a base into a reaction vessel, carrying out the reaction, and after post-processing, obtaining deuterated dichloromethane; The reactive deuterium substrate is selected from R1 ND2, R 2 R 3 ND, R 1 OD, deuterated diamine, deuterated diol, deuterated triamine, or deuterated triol; R 1 Selected from substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted 3-10 cycloalkyl, substituted or unsubstituted 3-10 heterocycloalkyl, substituted or unsubstituted 6-10 aryl, substituted or unsubstituted 5-10 heteroaryl; R 1 In this context, the substituents of the substituted C1-C10 alkyl group are selected from C1-C4 alkoxy, 3-6 membered cycloalkyl, halogen, morpholinyl, tetrahydropyrroleyl, 6-10 membered aryl, pyridinyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl. R 1 In this context, the substituents of the substituted 3-10 cycloalkyl, substituted 3-10 heterocycloalkyl, substituted 6-10 aryl, and substituted 5-10 heteroaryl are selected from C1-C6 alkyl, C1-C6 alkoxy, 3-6 cycloalkyl, halogen, morpholino, tetrahydropyrrole, 6-10 aryl, pyridinyl, quinolino, isoquinolino, thiopheno, furanyl, thiazolyl, oxazolyl, benzothiopheno, or benzofuranyl. R 1 In this context, the 3-10 heterocyclic alkyl groups contain 1-2 heteroatoms selected from N, S, and O; R 1 In this context, the 5-10 member heteroaryl group is selected from pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; R 2 R 3 Independently selected from D, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted 3-10 cycloalkyl, substituted or unsubstituted 3-10 heterocycloalkyl, substituted or unsubstituted 6-10 aryl, substituted or unsubstituted 5-10 heteroaryl, and R 2 R 3 Not both D; or, R 2 R 3 It connects with ND to form a 3-12 membered alkyl heterocycle; R 2 R 3 In this context, the substituents of the substituted C1-C10 alkyl group are selected from C1-C4 alkoxy, 3-6 membered cycloalkyl, halogen, morpholinyl, tetrahydropyrroleyl, 6-10 membered aryl, pyridinyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl. R2 R 3 In this context, the substituents of the substituted 3-10 cycloalkyl, substituted 3-10 heterocycloalkyl, substituted 6-10 aryl, and substituted 5-10 heteroaryl are selected from C1-C6 alkyl, C1-C6 alkoxy, 3-6 cycloalkyl, halogen, morpholino, tetrahydropyrrole, 6-10 aryl, pyridinyl, quinolino, isoquinolino, thiopheno, furanyl, thiazolyl, oxazolyl, benzothiopheno, or benzofuranyl. R 2 R 3 In this context, the 3-10 heterocyclic alkyl groups contain 1-2 heteroatoms selected from N, S, and O; R 2 R 3 In this context, the 5-10 member heteroaryl group is selected from pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; R 2 R 3 In, the R 2 R 3 In the 3-12 membered alkyl heterocycles formed by the connection with ND, in addition to the N of ND, there are 0-2 S or O heteroatoms; The structural formula of the deuterated diamine is: R 4 -ND-X-ND-R 5 Alternatively, the deuterated diamine is selected from 4- to 10-membered alkyl heterocycles containing only 2 ND groups or only 1 ND group and 1 ND2 group; The structural formula of the deuterated diol is: DO-X-OD; R 4 R 5 Independently selected from D, C1-C10 alkyl, 3-10 membered cycloalkyl, 6-10 membered aryl, pyridyl; X is selected from -(CH2) n - 3-10 membered cycloalkyl, 6-10 membered aryl, pyridyl, where n is an integer selected from 1 to 10; The deuterated triamine is selected from... or ; The deuterated triol is selected from , or ; The structural formula of the deuterated phosphine oxide compound is: ; R 6 R 7Independently selected from substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3-10 membered cycloalkyl, substituted or unsubstituted 6-10 membered aryloxy, substituted or unsubstituted 6-10 membered arylmethyl, substituted or unsubstituted 6-10 membered arylmethoxy; R 6 R 7 In this context, the substituents of the substituted C1-C4 alkyl groups and substituted C1-C4 alkoxy groups are selected from 6-10 aryl groups and halogens; R 6 R 7 In this context, the substituents of the substituted 3-10 cycloalkyl, substituted 6-10 aryl, substituted 6-10 aryloxy, substituted 6-10 arylmethyl, and substituted 6-10 arylmethoxy groups are selected from C1-C4 alkyl, C1-C4 alkoxy, 6-10 aryl, or halogens. The cationic organic small molecule catalyst is a quaternary ammonium salt N(R) 8 )4Y or quaternary phosphonium salt P(R) 9 )3R 10 Y; Y is selected from fluoride ion, chloride ion, bromide ion or iodide ion; R 8 Selected from C1~C16 alkyl groups; R 9 Selected from 6-10 aryl-substituted or unsubstituted C1-C4 alkyl, halogen-substituted or 5-6 membered cycloalkyl or C1-C4 alkyl-substituted or C1-C4 alkoxy-substituted or unsubstituted phenyl groups; R 10 Selected from 6-10 aryl-substituted or unsubstituted C1-C4 alkyl, halogen-substituted, or 5-6 membered cycloalkyl or C1-C4 alkyl-substituted or C1-C4 alkoxy-substituted or unsubstituted phenyl groups.

[0007] In the above-mentioned method for synthesizing deuterated dichloromethane, R 1 Selected from substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted 3-6 cycloalkyl groups, substituted or unsubstituted 3-6 heterocycloalkyl groups, substituted or unsubstituted 6-10 aryl groups, and substituted or unsubstituted 5-10 heteroaryl groups; R 1 In this context, the substituents of the substituted C1-C6 alkyl groups are selected from methoxy, ethoxy, cyclohexyl, halogen, morpholinyl, tetrahydropyrrolyl, phenyl, pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; R 1In this context, the substituents of the substituted 3-6 cycloalkyl, substituted 3-6 heterocycloalkyl, substituted 6-10 aryl, and substituted 5-10 heteroaryl are selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-hexyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, cyclohexyl, halogen, morpholino, tetrahydropyrrolyl, phenyl, naphthyl, pyridyl, quinolino, isoquinolino, thiophene, furanyl, thiazolyl, oxazolyl, benzothiophene, or benzofuranyl; R 1 In this context, the 3-6 heterocyclic alkyl group contains one heteroatom selected from N, S, and O; R 1 In this context, the 5-10 heteroaryl group is selected from pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl.

[0008] Preferably, in the above-mentioned method for synthesizing deuterated dichloromethane, R1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, cyclohexyl, tetrahydrofuranyl, tetrahydrothiophene, benzyl, phenyl, methyl-substituted phenyl, methoxy-substituted phenyl, tert-butyl-substituted phenyl, halogen-substituted phenyl, phenyl-substituted phenyl, N-morpholinyl-substituted phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl, thiophene, furanyl, thiazolyl, oxazolyl, benzothiophene, or benzofuranyl.

[0009] More preferably, in the above-described method for synthesizing deuterated dichloromethane, R1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, cyclohexyl, tetrahydrofuranyl, tetrahydrothiophenyl, benzyl, 2-pyridyl-methyl, 3-pyridyl-methyl, phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 2-methoxyphenyl, 2-naphthyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-phenylphenyl, 4-(N-morpholinyl)phenyl, 2-pyridyl, 3-pyridyl, 6-quinolinyl, and thiazolyl.

[0010] Most preferably, in the above-mentioned method for synthesizing deuterated dichloromethane, the R... 1 ND2 is selected from methyl-ND2, ethyl-ND2, n-propyl-ND2, isopropyl-ND2, n-butyl-ND2, tert-butyl-ND2, n-pentyl-ND2, n-hexyl-ND2, cyclohexyl-ND2, benzyl-ND2, phenyl-ND2, p-tolyl-ND2, p-methoxyphenyl-ND2, 2-naphthyl-ND2, 4-fluorophenyl-ND2, 4-tert-butylphenyl-ND2, 3-pyridyl-ND2, or 6-ND2-quinoline; R 1OD is selected from methyl-OD, ethyl-OD, n-propyl-OD, isopropyl-OD, n-butyl-OD, tert-butyl-OD, n-pentyl-OD, n-hexyl-OD, cyclohexyl-OD, benzyl-OD, phenyl-OD, p-tolyl-OD, p-methoxyphenyl-OD, 2-naphthyl-OD, 4-fluorophenyl-OD, 4-tert-butylphenyl-OD, 3-pyridyl-OD, or 6-OD-quinoline.

[0011] In the above-mentioned method for synthesizing deuterated dichloromethane, R 2 R 3 Independently selected from D, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted 3-6 cycloalkyl, substituted or unsubstituted 3-6 heterocycloalkyl, substituted or unsubstituted 6-10 aryl, substituted or unsubstituted 5-10 heteroaryl, and R 2 R 3 Not both D; or, R 2 R 3 It forms a 4-10 membered alkyl heterocycle by attaching to ND; R 2 R 3 In this context, the substituents of the substituted C1-C6 alkyl groups are selected from methoxy, ethoxy, cyclohexyl, halogen, morpholinyl, tetrahydropyrrolyl, phenyl, pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; R 2 R 3 In this context, the substituents of the substituted 3-6 cycloalkyl, substituted 3-6 heterocycloalkyl, substituted 6-10 aryl, and substituted 5-10 heteroaryl are selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-hexyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, cyclohexyl, halogen, morpholino, tetrahydropyrrolyl, phenyl, naphthyl, pyridyl, quinolino, isoquinolino, thiophene, furanyl, thiazolyl, oxazolyl, benzothiophene, or benzofuranyl; R 2 R 3 In this context, the 3-6 heterocyclic alkyl group contains one heteroatom selected from N, S, and O; R 2 R 3 In this context, the 5-10 membered heteroaryl group is selected from pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; R 2 R 3 In, the R 2 R 3 In the 4- to 10-membered alkyl heterocycles formed by the connection with ND, in addition to the N in ND, there are 0 to 1 S or O heteroatoms.

[0012] Preferably, in the above-mentioned method for synthesizing deuterated dichloromethane, R 2 R3 Independently selected from D, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, cyclohexyl, tetrahydrofuranyl, tetrahydrothiophene, benzyl, phenyl, methyl-substituted phenyl, methoxy-substituted phenyl, tert-butyl-substituted phenyl, halogen-substituted phenyl, phenyl-substituted phenyl, N-morpholinyl-substituted phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl, thiophene, furanyl, thiazolyl, oxazolyl, benzothiophene, or benzofuranyl, and R 2 R 3 Not both D; or, R 2 R 3 It can be linked with ND to form ND morpholine, ND aziridine, ND tetrahydropyrrole, ND hexahydropyridine, ND aziridine heptane or ND aziridine octane.

[0013] More preferably, in the above-described method for synthesizing deuterated dichloromethane, R 2 R 3 Independently selected from D, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, cyclohexyl, tetrahydrofuranyl, tetrahydrothiopheneyl, benzyl, 2-pyridyl-methyl, 3-pyridyl-methyl, phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 2-methoxyphenyl, 2-naphthyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-phenylphenyl, 4-(N-morpholinyl)phenyl, 2-pyridyl, 3-pyridyl, 6-quinolinyl, thiazolyl, and R 2 R 3 Not both D; or, R 2 R 3 It can be linked with ND to form ND morpholine, ND aziridine, ND tetrahydropyrrole, ND hexahydropyridine, ND aziridine heptane or ND aziridine octane.

[0014] Most preferably, in the above-mentioned method for synthesizing deuterated dichloromethane, the R... 2 R 3ND is selected from (methyl)2-ND, (ethyl)2-ND, (n-propyl)2-ND, (isopropyl)2-ND, (n-butyl)2-ND, (tert-butyl)2-ND, (n-pentyl)2-ND, (n-hexyl)2-ND, (cyclohexyl)2-ND, (benzyl)2-ND, (phenyl)2-ND, (p-tolyl)2-ND, (p-methoxyphenyl)2-ND, (2-naphthyl)2-ND, (4-fluorophenyl)2-ND, (4-tert-butylphenyl)2-ND, (3-pyridyl)2-ND, (6-quinoline)2-ND, ND morpholine, ND azacyclobutane, ND tetrahydropyrrole, ND hexahydropyridine, ND azacycloheptane, or ND azacyclooctane (i.e., in morpholine, azacyclobutane, etc., the H in NH is deuterated).

[0015] In the above-mentioned method for synthesizing deuterated dichloromethane, the deuterated diamine has the following structural formula: R 4 -ND-X-ND-R 5 Alternatively, the deuterated diamine is selected from 4- to 8-membered alkyl heterocycles containing only 2 ND groups, or only 1 ND group and 1 ND2 group; the deuterated diol has the structural formula: DO-X-OD; R 4 R 5 Independently selected from D, C1-C6 alkyl, 3-6 membered cycloalkyl, 6-10 membered aryl, pyridyl; X selected from -(CH2). n - 3-6 membered cycloalkyl, 6-10 membered aryl, pyridyl, n is selected from integers from 2 to 8.

[0016] Preferably, in the above method for synthesizing deuterated dichloromethane, the deuterated diamine has the following structural formula: R 4 -ND-X-ND-R 5 Alternatively, the deuterated diamine is selected from 4- to 6-membered alkyl heterocycles containing only 2 ND groups, or only 1 ND group and 1 ND2 group; the deuterated diol has the structural formula: DO-X-OD; R 4 R 5 Independently selected from D, C1-C4 alkyl, cyclohexyl, phenyl, pyridyl; X is selected from -(CH2). n - Cyclohexyl, phenyl, pyridyl, n is an integer selected from 2 to 6.

[0017] More preferably, in the above method for synthesizing deuterated dichloromethane, the deuterated diamine is selected from... , , , , , , , or The deuterated diol is selected from... , , , , or .

[0018] In the above-mentioned method for synthesizing deuterated dichloromethane, X is selected from... Ring A is selected from 3-10 membered cycloalkyl, 6-10 membered aryl or pyridyl, and X1 and X2 are independently selected from C1-C6 alkyl chains.

[0019] Preferably, in the above method for synthesizing deuterated dichloromethane, X is selected from... Ring A is selected from 3-6 membered cycloalkyl, phenyl, naphthyl or pyridyl, and X1 and X2 are independently selected from C1-C4 alkyl chains.

[0020] This invention is applicable to a wide range of active deuterium substrates, including not only deuterated monoamines and deuterated monools, but also deuterated diamines, deuterated triamines, deuterated diols, and deuterated triols; the amines can be either two-D or one-D; and not only alkyl-chain deuterated amines, but also deuterated azaalkyl rings. Therefore, the method of this invention has excellent versatility, and the above description does not actually cover all compounds applicable to this method.

[0021] In the above-mentioned method for synthesizing deuterated dichloromethane, R 6 R 7 Independently selected from substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3-6 membered cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenoxy, substituted or unsubstituted benzyl, substituted or unsubstituted benzoxy; R 6 R 7 In this context, the substituents of the substituted C1-C4 alkyl group and the substituted C1-C4 alkoxy group are selected from phenyl, fluorine, chlorine, bromine, and iodine; R 6 R 7 In this context, the substituents of the substituted 3-6 membered cycloalkyl, substituted phenyl, substituted phenoxy, substituted benzyl, and substituted benzoxy are selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, aryl, fluorine, chlorine, bromine, or iodine.

[0022] Preferably, in the above-mentioned method for synthesizing deuterated dichloromethane, R 6 R 7It is independently selected from methyl, methoxy, ethyl, ethoxy, tert-butyl, tert-butoxy, phenoxy, benzyl, benzyloxy, 4-methylphenyl, 4-methoxyphenyl, 4-biphenyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl or 3,5-dimethylphenyl.

[0023] More preferably, in the above-described method for synthesizing deuterated dichloromethane, the deuterated phosphine oxide compound is selected from (CH3)2P(O)D, (cyclohexyl)2P(O)D, (CH3O)2P(O)D, Ph2P(O)D, (PhCH2)2P(O)D, (4-MeO-C6H4)2P(O)D, (4-Me-C6H4)2P(O)D, (4-F-C6H4)2P(O)D, (4-Cl-C6H4)2P(O)D, or (4-Br-C6H4)2P(O)D.

[0024] In the above-mentioned method for synthesizing deuterated dichloromethane, R 8 Selected from methyl, n-butyl, tert-butyl, and hexadecyl; R 9 Selected from methyl, cyclohexyl, phenyl, benzyl, 4-methoxyphenyl, 4-fluorophenyl; R 10 Selected from methyl, cyclohexyl, phenyl, benzyl, 4-methoxyphenyl, and 4-fluorophenyl.

[0025] Preferably, in the above-mentioned method for synthesizing deuterated dichloromethane, the cationic organic small molecule catalyst is selected from NBu4Br, NBu4I, PCy3MeBr, PCy3MeI, PPh3MeBr or PPh3MeI.

[0026] In the above-mentioned method for synthesizing deuterated dichloromethane, when the active deuterium substrate is R... 1 ND2, R 2 R 3 ND or R 1 At OD, the molar ratio of the deuterated chloroform, the active deuterated substrate, the deuterated phosphine oxide compound, the cationic small organic molecule catalyst and the base is 1~30:1:1~3:0.01~0.2:1~3.

[0027] Preferably, in the above method for synthesizing deuterated dichloromethane, when the active deuterium substrate is R... 1 ND2, R 2 R 3 ND or R 1 At OD, the molar ratio of the deuterated chloroform, the active deuterated substrate, the deuterated phosphine oxide compound, the cationic small organic molecule catalyst and the base is 1~30:1:1~2:0.01~0.2:1~2.

[0028] In the above-mentioned method for synthesizing deuterated dichloromethane, when the active deuterated substrate is a deuterated diamine or a deuterated diol, the molar ratio of the deuterated chloroform, the active deuterated substrate, the deuterated phosphine oxide compound, the cationic small organic molecule catalyst, and the base is 2~60:1:2~6:0.01~0.4:2~6.

[0029] Preferably, in the above-mentioned method for synthesizing deuterated dichloromethane, when the active deuterium substrate is a deuterated diamine or a deuterated diol, the molar ratio of the deuterated chloroform, the active deuterium substrate, the deuterated phosphine oxide compound, the cationic small organic molecule catalyst, and the base is 2~60:1:2~4:0.01~0.4:2~4.

[0030] In the above-mentioned method for synthesizing deuterated dichloromethane, when the active deuterated substrate is a deuterated triamine or a deuterated triol, the molar ratio of the deuterated chloroform, the active deuterated substrate, the deuterated phosphine oxide compound, the cationic small organic molecule catalyst, and the base is 3~90:1:3~9:0.01~0.6:3~9.

[0031] Preferably, in the above method for synthesizing deuterated dichloromethane, when the active deuterated substrate is a deuterated triamine or a deuterated triol, the molar ratio of the deuterated chloroform, the active deuterated substrate, the deuterated phosphine oxide compound, the cationic small organic molecule catalyst, and the base is 3~90:1:3~6:0.01~0.6:3~6.

[0032] In the above-mentioned method for synthesizing deuterated dichloromethane, the base is selected from sodium hydroxide, potassium hydroxide, sodium phosphate, potassium phosphate, potassium carbonate, sodium carbonate, cesium carbonate, lithium tert-butoxide, sodium tert-butoxide, sodium ethoxide, sodium methoxide, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]-5-nonene, 7-methylhexa-bicyclic guanidine, 1,5,7-triazabicyclo[4.4.0]dec-5-ene, tetramethylguanidine, triethylenediamine, or triethylamine.

[0033] Preferably, in the above-mentioned method for synthesizing deuterated dichloromethane, the base is selected from 1,8-diazabicyclo[5.4.0]undec-7-ene or cesium carbonate.

[0034] In the above-mentioned method for synthesizing deuterated dichloromethane, the reaction temperature is room temperature to 50°C. o C.

[0035] Preferably, in the above-described method for synthesizing deuterated dichloromethane, the reaction temperature is room temperature.

[0036] In the above-mentioned method for synthesizing deuterated dichloromethane, the reaction time is 1 to 24 hours.

[0037] Preferably, in the above-described method for synthesizing deuterated dichloromethane, the reaction time is 1 to 2 hours.

[0038] In the above-mentioned method for synthesizing deuterated dichloromethane, the post-processing operation is as follows: filtering to remove insoluble matter and distilling under normal pressure to obtain the deuterated dichloromethane product.

[0039] In the above-mentioned synthesis method of deuterated dichloromethane, deuterated dichloromethane can be prepared without the addition of a cationic small organic molecule catalyst.

[0040] The above-mentioned method for synthesizing deuterated dichloromethane further includes adding an organic solvent to a reaction vessel; the organic solvent is selected from at least one of petroleum ether, n-hexane, n-heptane, cyclohexane, toluene, xylene, diethyl ether, deuterated chloroform, tetrahydrofuran, 1,4-dioxane, acetonitrile, or N,N-dimethylformamide.

[0041] Preferably, in the above-described method for synthesizing deuterated dichloromethane, the organic solvent is selected from at least one of toluene, xylene, diethyl ether, deuterated chloroform, tetrahydrofuran, 1,4-dioxane, acetonitrile, or N,N-dimethylformamide.

[0042] More preferably, in the above method for synthesizing deuterated dichloromethane, the organic solvent is selected from at least one of toluene, xylene, deuterated chloroform, or acetonitrile.

[0043] In the above-mentioned method for synthesizing deuterated dichloromethane, the molar ratio of the organic solvent to the active deuterium substrate is 5~50:1.

[0044] The beneficial effects of this invention are: This invention provides a method for the efficient preparation of deuterated dichloromethane from deuterated chloroform under mild reaction conditions. The method can be carried out smoothly at or near room temperature. The reaction uses deuterated chloroform as the main raw material, and involves deuterated phosphine oxide compounds and reactive deuterium substrates (such as R...). 1 ND2, R 2 R 3 ND, R 1 Deuterated dichloromethane can be readily produced by reacting with OD, bases, cationic small molecule organic catalysts, and aprotic organic solvents. This reaction strategy is carried out under mild reaction conditions, and the byproducts can be directly sold as products or recycled, greatly reducing the environmental impact and effectively lowering the product preparation cost. Detailed Implementation

[0045] The present invention will be further described in detail below through embodiments, but the scope of protection of the present invention is not limited to the embodiments described herein.

[0046] Example 1 Deuterated chloroform (100 mmol), PhOD (10 mmol), Ph₂P(O)D (10 mmol), PPh₃MeI (1 mmol), and cesium carbonate (10 mmol) were added sequentially to a reaction vessel, and the mixture was stirred at room temperature for 1 hour. After the reaction was complete, insoluble matter was removed by filtration, and the product was distilled under normal pressure to obtain deuterated dichloromethane product with a yield of 90% and a deuterium content of 99%.

[0047] The deuterated dichloromethane product was confirmed by NMR (5.29 ppm was CH2Cl2, 5.27 ppm was CHDCl2) and GC-MS.

[0048] Example 2 Deuterated chloroform (10 mmol), PhOD (10 mmol), Ph₂P(O)D (10 mmol), PPh₃MeI (1 mmol), cesium carbonate (10 mmol), and toluene (100 mmol) were added sequentially to a reaction vessel, and the mixture was stirred at room temperature for 1 hour. After the reaction was complete, insoluble matter was removed by filtration, and the product, deuterated dichloromethane, was obtained by atmospheric distillation with a yield of 91% and a deuterium content of 99%.

[0049] Based on Example 2, the present invention also tested the effect of the catalyst on the reaction. As shown in Table 1. Due to the high activity of phenolic compounds, the catalyst had little effect on the yield of deuterated dichloromethane, with the product yield remaining around 90%.

[0050] Table 1 Effect of catalyst on reaction

[0051] Based on Example 2, this invention further tested the effect of solvents. As shown in Table 2, except for petroleum ether and n-hexane, which have too low polarity and result in incomplete dissolution of the reactants, the conversion rates in other solvents were around 90%.

[0052] Table 2 Effect of solvent on reaction

[0053] Based on Example 2, the present invention further tested the effect of bases. The results are shown in Table 3. The results show that cesium carbonate, 1,8-diazabicyclo[5.4.0]undec-7-ene and similar organic bases can efficiently generate the product, but other bases are less effective.

[0054] Table 3 Effect of base on reaction

[0055] Example 3 Deuterated chloroform (10 mmol), MeOD (10 mmol), Ph₂P(O)D (10 mmol), PPh₃MeI (1 mmol), cesium carbonate (10 mmol), and toluene (100 mmol) were added sequentially to a reaction vessel, and the mixture was stirred at room temperature for 1 hour. After the reaction was complete, insoluble matter was removed by filtration, and the product was distilled under atmospheric pressure to obtain deuterated dichloromethane with a yield of 91% and a deuterium content of 99%.

[0056] Building upon Example 3, this invention further tested the effects of substituents in the alcohol and phosphine oxide on the reaction. The structures of the compounds used are as follows. The use of these raw materials had almost no effect on the use of deuterated dichloromethane, maintaining it at approximately 90%.

[0057] Table 4 Alcohol Substituents (R) 1 The effect of -OD) on the reaction

[0058] Table 5 Phosphine oxide substituents (R) 6 R 7 The effect of P(O)D on the reaction

[0059] Example 4 Deuterated chloroform (10 mmol), PhND2 (10 mmol), Ph2P(O)D (10 mmol), PPh3MeI (1 mmol), cesium carbonate (10 mmol), and toluene (100 mmol) were added sequentially to the reaction vessel and heated to 50 °C. o The reaction was stirred at C for 1 hour. After the reaction was completed, the insoluble matter was removed by filtration, and the product was distilled at atmospheric pressure to obtain deuterated dichloromethane with a yield of 85% and a deuterium content of 99%.

[0060] Example 5 Deuterated chloroform (10 mmol), C6H 13 ND2 (10 mmol), Ph2P(O)D (10 mmol), PPh3MeI (1 mmol), cesium carbonate (10 mmol), and toluene (100 mmol) were added sequentially to the reaction vessel, and the mixture was heated to 50 °C. o The reaction was stirred at C for 1 hour. After the reaction was completed, the insoluble matter was removed by filtration, and the product was distilled at atmospheric pressure to obtain deuterated dichloromethane with a yield of 88% and a deuterium content of 99%.

[0061] Example 6 Deuterated chloroform (10 mmol), (C6H) 132ND (10 mmol), Ph2P(O)D (10 mmol), PPh3MeI (1 mmol), cesium carbonate (10 mmol), and toluene (100 mmol) were added sequentially to the reaction vessel, and the mixture was heated to 50 °C. o The reaction was stirred at C for 1 hour. After the reaction was completed, the insoluble matter was removed by filtration, and the product was distilled at atmospheric pressure to obtain deuterated dichloromethane with a yield of 80% and a deuterium content of 99%.

[0062] Example 7 Deuterated chloroform (10 mmol), (3-C5H5N)ND2 (pyridine-3-amine, 10 mmol), Ph2P(O)D (10 mmol), PPh3MeI (1 mmol), cesium carbonate (10 mmol), and toluene (100 mmol) were added sequentially to the reaction vessel and heated to 50 °C. o The reaction was stirred at C for 1 hour. After the reaction was completed, the insoluble matter was removed by filtration, and the product was distilled at atmospheric pressure to obtain deuterated dichloromethane with a yield of 70% and a deuterium content of 99%.

[0063] Example 8 Deuterated chloroform (10 mmol), d2-1,4-benzyl diethanol (10 mmol), Ph2P(O)D (20 mmol), PPh3MeI (1 mmol), cesium carbonate (20 mmol), and toluene (100 mmol) were added sequentially to a reaction vessel, and the mixture was stirred at room temperature for 1 hour. After the reaction was complete, insoluble matter was removed by filtration, and the product was distilled under normal pressure to obtain deuterated dichloromethane in 43% yield with a deuterium content of 99%.

Claims

1. A method for synthesizing deuterated dichloromethane, characterized in that: Includes the following steps: Deuterated chloroform, an active deuterated substrate, a deuterated phosphine oxide compound, a cationic small organic molecule catalyst, and a base were added to a reaction vessel to carry out the reaction. After the reaction was completed, the product was post-processed to obtain deuterated dichloromethane. The reactive deuterium substrate is selected from R 1 ND2, R 2 R 3 ND, R 1 OD, deuterated diamine, deuterated diol, deuterated triamine, or deuterated triol; R 1 Selected from substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted 3-10 cycloalkyl, substituted or unsubstituted 3-10 heterocycloalkyl, substituted or unsubstituted 6-10 aryl, substituted or unsubstituted 5-10 heteroaryl; R 1 In this context, the substituents of the substituted C1-C10 alkyl group are selected from C1-C4 alkoxy, 3-6 membered cycloalkyl, halogen, morpholinyl, tetrahydropyrroleyl, 6-10 membered aryl, pyridinyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl. R 1 In this context, the substituents of the substituted 3-10 cycloalkyl, substituted 3-10 heterocycloalkyl, substituted 6-10 aryl, and substituted 5-10 heteroaryl are selected from C1-C6 alkyl, C1-C6 alkoxy, 3-6 cycloalkyl, halogen, morpholino, tetrahydropyrrole, 6-10 aryl, pyridinyl, quinolino, isoquinolino, thiopheno, furanyl, thiazolyl, oxazolyl, benzothiopheno, or benzofuranyl. R 1 In this context, the 3-10 heterocyclic alkyl groups contain 1-2 heteroatoms selected from N, S, and O; R 1 In this context, the 5-10 member heteroaryl group is selected from pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; R 2 R 3 Independently selected from D, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted 3-10 cycloalkyl, substituted or unsubstituted 3-10 heterocycloalkyl, substituted or unsubstituted 6-10 aryl, substituted or unsubstituted 5-10 heteroaryl, and R 2 R 3 Not both D; or, R 2 R 3 It connects with ND to form a 3-12 membered alkyl heterocycle; R 2 R 3 In this context, the substituents of the substituted C1-C10 alkyl group are selected from C1-C4 alkoxy, 3-6 membered cycloalkyl, halogen, morpholinyl, tetrahydropyrroleyl, 6-10 membered aryl, pyridinyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl. R 2 R 3 In this context, the substituents of the substituted 3-10 cycloalkyl, substituted 3-10 heterocycloalkyl, substituted 6-10 aryl, and substituted 5-10 heteroaryl are selected from C1-C6 alkyl, C1-C6 alkoxy, 3-6 cycloalkyl, halogen, morpholino, tetrahydropyrrole, 6-10 aryl, pyridinyl, quinolino, isoquinolino, thiopheno, furanyl, thiazolyl, oxazolyl, benzothiopheno, or benzofuranyl. R 2 R 3 In this context, the 3-10 heterocyclic alkyl groups contain 1-2 heteroatoms selected from N, S, and O; R 2 R 3 In this context, the 5-10 member heteroaryl group is selected from pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; R 2 R 3 In, the R 2 R 3 In the 3-12 membered alkyl heterocycles formed by the connection with ND, in addition to the N of ND, there are 0-2 S or O heteroatoms; The structural formula of the deuterated diamine is: R 4 -ND-X-ND-R 5 Alternatively, the deuterated diamine is selected from 4- to 10-membered alkyl heterocycles containing only 2 ND groups or only 1 ND group and 1 ND2 group; The structural formula of the deuterated diol is: DO-X-OD; R 4 R 5 Independently selected from D, C1-C10 alkyl, 3-10 membered cycloalkyl, 6-10 membered aryl, pyridyl; X is selected from -(CH2) n - 3-10 membered cycloalkyl, 6-10 membered aryl, pyridyl, where n is an integer selected from 1 to 10; The deuterated triamine is selected from... or ; The deuterated triol is selected from , or ; The structural formula of the deuterated phosphine oxide compound is: ; R 6 R 7 Independently selected from substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3-10 membered cycloalkyl, substituted or unsubstituted 6-10 membered aryloxy, substituted or unsubstituted 6-10 membered arylmethyl, substituted or unsubstituted 6-10 membered arylmethoxy; R 6 R 7 In this context, the substituents of the substituted C1-C4 alkyl groups and substituted C1-C4 alkoxy groups are selected from 6-10 aryl groups and halogens; R 6 R 7 In this context, the substituents of the substituted 3-10 cycloalkyl, substituted 6-10 aryl, substituted 6-10 aryloxy, substituted 6-10 arylmethyl, and substituted 6-10 arylmethoxy groups are selected from C1-C4 alkyl, C1-C4 alkoxy, 6-10 aryl, or halogens. The cationic organic small molecule catalyst is a quaternary ammonium salt N(R) 8 )4Y or quaternary phosphonium salt P(R) 9 )3R 10 Y; Y is selected from fluoride ion, chloride ion, bromide ion or iodide ion; R 8 Selected from C1~C16 alkyl groups; R 9 Selected from 6-10 aryl-substituted or unsubstituted C1-C4 alkyl, halogen-substituted or 5-6 membered cycloalkyl or C1-C4 alkyl-substituted or C1-C4 alkoxy-substituted or unsubstituted phenyl groups; R 10 Selected from 6-10 aryl-substituted or unsubstituted C1-C4 alkyl, halogen-substituted, or 5-6 membered cycloalkyl or C1-C4 alkyl-substituted or C1-C4 alkoxy-substituted or unsubstituted phenyl groups.

2. The method for synthesizing deuterated dichloromethane according to claim 1, characterized in that: R 1 Selected from substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted 3-6 cycloalkyl groups, substituted or unsubstituted 3-6 heterocycloalkyl groups, substituted or unsubstituted 6-10 aryl groups, and substituted or unsubstituted 5-10 heteroaryl groups; R 1 In this context, the substituents of the substituted C1-C6 alkyl groups are selected from methoxy, ethoxy, cyclohexyl, halogen, morpholinyl, tetrahydropyrrolyl, phenyl, pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; R 1 In this context, the substituents of the substituted 3-6 cycloalkyl, substituted 3-6 heterocycloalkyl, substituted 6-10 aryl, and substituted 5-10 heteroaryl are selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-hexyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, cyclohexyl, halogen, morpholino, tetrahydropyrrolyl, phenyl, naphthyl, pyridyl, quinolino, isoquinolino, thiophene, furanyl, thiazolyl, oxazolyl, benzothiophene, or benzofuranyl; R 1 In this context, the 3-6 heterocyclic alkyl group contains one heteroatom selected from N, S, and O; R 1 In this context, the 5-10 member heteroaryl group is selected from pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; Preferably, R1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, cyclohexyl, tetrahydrofuranyl, tetrahydrothiophenyl, benzyl, phenyl, methyl-substituted phenyl, methoxy-substituted phenyl, tert-butyl-substituted phenyl, halogen-substituted phenyl, phenyl-substituted phenyl, N-morpholinyl-substituted phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; More preferably, R1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, cyclohexyl, tetrahydrofuranyl, tetrahydrothiophenyl, benzyl, 2-pyridyl-methyl, 3-pyridyl-methyl, phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 2-methoxyphenyl, 2-naphthyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-phenylphenyl, 4-(N-morpholinyl)phenyl, 2-pyridyl, 3-pyridyl, 6-quinolinyl, thiazolyl; Most preferably, the R 1 ND2 is selected from methyl-ND2, ethyl-ND2, n-propyl-ND2, isopropyl-ND2, n-butyl-ND2, tert-butyl-ND2, n-pentyl-ND2, n-hexyl-ND2, cyclohexyl-ND2, cyclohexyl-ND2, benzyl-ND2, phenyl-ND2, p-tolyl-ND2, p-methoxyphenyl-ND2, 2-naphthyl-ND2, 4-fluorophenyl-ND2, 4-tert-butylphenyl-ND2, 3-pyridyl-ND2, or 6-ND2-quinoline; R 1 OD is selected from methyl-OD, ethyl-OD, n-propyl-OD, isopropyl-OD, n-butyl-OD, tert-butyl-OD, n-pentyl-OD, n-hexyl-OD, cyclohexyl-OD, benzyl-OD, phenyl-OD, p-tolyl-OD, p-methoxyphenyl-OD, 2-naphthyl-OD, 4-fluorophenyl-OD, 4-tert-butylphenyl-OD, 3-pyridyl-OD, or 6-OD-quinoline.

3. The method for synthesizing deuterated dichloromethane according to claim 1, characterized in that: R 2 R 3 Independently selected from D, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted 3-6 cycloalkyl, substituted or unsubstituted 3-6 heterocycloalkyl, substituted or unsubstituted 6-10 aryl, substituted or unsubstituted 5-10 heteroaryl, and R 2 R 3 Not both D; or, R 2 R 3 It forms a 4-10 membered alkyl heterocycle by attaching to ND; R 2 R 3 In this context, the substituents of the substituted C1-C6 alkyl groups are selected from methoxy, ethoxy, cyclohexyl, halogen, morpholinyl, tetrahydropyrrolyl, phenyl, pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; R 2 R 3 In this context, the substituents of the substituted 3-6 cycloalkyl, substituted 3-6 heterocycloalkyl, substituted 6-10 aryl, and substituted 5-10 heteroaryl are selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-hexyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, cyclohexyl, halogen, morpholino, tetrahydropyrrolyl, phenyl, naphthyl, pyridyl, quinolino, isoquinolino, thiophene, furanyl, thiazolyl, oxazolyl, benzothiophene, or benzofuranyl; R 2 R 3 In this context, the 3-6 heterocyclic alkyl group contains one heteroatom selected from N, S, and O; R 2 R 3 In this context, the 5-10 membered heteroaryl group is selected from pyridyl, quinolinyl, isoquinolinyl, thiophenyl, furanyl, thiazolyl, oxazolyl, benzothiophenyl, or benzofuranyl; R 2 R 3 In, the R 2 R 3 In the 4- to 10-membered alkyl heterocycles formed by the connection with ND, in addition to the N of ND, there are 0 to 1 S or O heteroatoms. Preferred, R 2 R 3 Independently selected from D, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, cyclohexyl, tetrahydrofuranyl, tetrahydrothiophene, benzyl, phenyl, methyl-substituted phenyl, methoxy-substituted phenyl, tert-butyl-substituted phenyl, halogen-substituted phenyl, phenyl-substituted phenyl, N-morpholinyl-substituted phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl, thiophene, furanyl, thiazolyl, oxazolyl, benzothiophene, or benzofuranyl, and R 2 R 3 Not both D; or, R 2 R 3 It can be linked with ND to form ND morpholine, ND aziridine, ND tetrahydropyrrole, ND hexahydropyridine, ND aziridine heptane or ND aziridine octane; More preferably, R 2 R 3 Independently selected from D, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, cyclohexyl, tetrahydrofuranyl, tetrahydrothiopheneyl, benzyl, 2-pyridyl-methyl, 3-pyridyl-methyl, phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 2-methoxyphenyl, 2-naphthyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-phenylphenyl, 4-(N-morpholinyl)phenyl, 2-pyridyl, 3-pyridyl, 6-quinolinyl, thiazolyl, and R 2 R 3 Not both D; or, R 2 R 3 It can be linked with ND to form ND morpholine, ND aziridine, ND tetrahydropyrrole, ND hexahydropyridine, ND aziridine heptane or ND aziridine octane; Most preferably, the R 2 R 3 ND is selected from (methyl)2-ND, (ethyl)2-ND, (n-propyl)2-ND, (isopropyl)2-ND, (n-butyl)2-ND, (tert-butyl)2-ND, (n-pentyl)2-ND, (n-hexyl)2-ND, (cyclohexyl)2-ND, (benzyl)2-ND, (phenyl)2-ND, (p-tolyl)2-ND, (p-methoxyphenyl)2-ND, (2-naphthyl)2-ND, (4-fluorophenyl)2-ND, (4-tert-butylphenyl)2-ND, (3-pyridyl)2-ND, (6-quinoline)2-ND, ND morpholine, ND aziridine, ND tetrahydropyrrole, ND hexahydropyridine, ND aziridine heptane, or ND aziridine octane.

4. The method for synthesizing deuterated dichloromethane according to claim 1, characterized in that: The structural formula of the deuterated diamine is: R 4 -ND-X-ND-R 5 Alternatively, the deuterated diamine is selected from 4- to 8-membered alkyl heterocycles containing only 2 ND groups, or only 1 ND group and 1 ND2 group; the deuterated diol has the structural formula: DO-X-OD; R 4 R 5 Independently selected from D, C1-C6 alkyl, 3-6 membered cycloalkyl, 6-10 membered aryl, pyridyl; X selected from -(CH2). n - 3-6 membered cycloalkyl, 6-10 membered aryl, pyridyl, n is selected from an integer from 2 to 8; Preferably, the structural formula of the deuterated diamine is: R 4 -ND-X-ND-R 5 Alternatively, the deuterated diamine is selected from 4- to 6-membered alkyl heterocycles containing only 2 ND groups, or only 1 ND group and 1 ND2 group; the deuterated diol has the structural formula: DO-X-OD; R 4 R 5 Independently selected from D, C1-C4 alkyl, cyclohexyl, phenyl, pyridyl; X is selected from -(CH2). n - Cyclohexyl, phenyl, pyridyl, n is an integer selected from 4 to 8; More preferably, the deuterated diamine is selected from... , , , , , , , or The deuterated diol is selected from... , , , , or ; Or, X is selected from Ring A is selected from 3-10 membered cycloalkyl, 6-10 membered aryl or pyridyl groups, and X1 and X2 are independently selected from C1-C6 alkyl chains; preferably, X is selected from... Ring A is selected from 3-6 membered cycloalkyl, phenyl, naphthyl or pyridyl, and X1 and X2 are independently selected from C1-C4 alkyl chains.

5. The method for synthesizing deuterated dichloromethane according to claim 1, characterized in that: R 6 R 7 Independently selected from substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy, substituted or unsubstituted 3-6 membered cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenoxy, substituted or unsubstituted benzyl, substituted or unsubstituted benzoxy; R 6 R 7 In this context, the substituents of the substituted C1-C4 alkyl group and the substituted C1-C4 alkoxy group are selected from phenyl, fluorine, chlorine, bromine, and iodine; R 6 R 7 In this context, the substituents of the substituted 3-6 membered cycloalkyl, substituted phenyl, substituted phenoxy, substituted benzyl, and substituted benzoxy are selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, aryl, fluorine, chlorine, bromine, or iodine. Preferred, R 6 R 7 It is independently selected from methyl, methoxy, ethyl, ethoxy, tert-butyl, tert-butoxy, phenoxy, benzyl, benzyloxy, 4-methylphenyl, 4-methoxyphenyl, 4-biphenyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl or 3,5-dimethylphenyl; More preferably, the deuterated phosphine oxide compound is selected from (CH3)2P(O)D, (cyclohexyl)2P(O)D, (CH3O)2P(O)D, Ph2P(O)D, (PhCH2)2P(O)D, (4-MeO-C6H4)2P(O)D, (4-Me-C6H4)2P(O)D, (4-F-C6H4)2P(O)D, (4-Cl-C6H4)2P(O)D, or (4-Br-C6H4)2P(O)D.

6. The method for synthesizing deuterated dichloromethane according to claim 1, characterized in that: R 8 Selected from methyl, n-butyl, tert-butyl, and hexadecyl; R 9 Selected from methyl, cyclohexyl, phenyl, benzyl, 4-methoxyphenyl, 4-fluorophenyl; R 10 Selected from methyl, cyclohexyl, phenyl, benzyl, 4-methoxyphenyl, and 4-fluorophenyl; Preferably, the cationic organic small molecule catalyst is selected from NBu4Br, NBu4I, PCy3MeBr, PCy3MeI, PPh3MeBr or PPh3MeI.

7. The method for synthesizing deuterated dichloromethane according to claim 1, characterized in that: When the reactive deuterium substrate is R 1 ND2, R 2 R 3 ND or R 1 At OD, the molar ratio of the deuterated chloroform, the active deuterated substrate, the deuterated phosphine oxide compound, the cationic small organic molecule catalyst, and the base is 1~30:1:1~3:0.01~0.2:1~3; preferably 1~30:1:1~2:0.01~0.2:1~2; When the active deuterium substrate is a deuterated diamine or a deuterated diol, the molar ratio of the deuterated chloroform, the active deuterium substrate, the deuterated phosphine oxide compound, the cationic small organic molecule catalyst, and the base is 2~60:1:2~6:0.01~0.4:2~6; preferably 2~60:1:2~4:0.01~0.4:2~4. When the active deuterium substrate is a deuterated triamine or a deuterated triol, the molar ratio of the deuterated chloroform, the active deuterium substrate, the deuterated phosphine oxide compound, the cationic small organic molecule catalyst, and the base is 3~90:1:3~9:0.01~0.6:3~9; preferably 3~90:1:3~6:0.01~0.6:3~6.

8. The method for synthesizing deuterated dichloromethane according to claim 1, characterized in that: At least one of the following must be met: The base is selected from sodium hydroxide, potassium hydroxide, sodium phosphate, potassium phosphate, potassium carbonate, sodium carbonate, cesium carbonate, lithium tert-butoxide, sodium tert-butoxide, sodium ethoxide, sodium methoxide, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]-5-nonene, 7-methylhexa-bicyclic guanidine, 1,5,7-triazabicyclo[4.4.0]dec-5-ene, tetramethylguanidine, triethylenediamine, or triethylamine; preferably, the base is selected from 1,8-diazabicyclo[5.4.0]undec-7-ene or cesium carbonate; The reaction temperature is room temperature to 50°C. o C; room temperature is preferred; The reaction time is 1 to 24 hours; preferably 1 to 2 hours. The post-processing operation is as follows: filtration to remove insoluble matter, and atmospheric distillation to obtain deuterated dichloromethane product.

9. The method for synthesizing deuterated dichloromethane according to any one of claims 1 to 8, characterized in that: No cationic organic small molecule catalysts are added.

10. The method for synthesizing deuterated dichloromethane according to any one of claims 1 to 9, characterized in that: The method also includes adding an organic solvent to the reaction vessel; the organic solvent is selected from at least one of petroleum ether, n-hexane, n-heptane, cyclohexane, toluene, xylene, diethyl ether, deuterated chloroform, tetrahydrofuran, 1,4-dioxane, acetonitrile, or N,N-dimethylformamide; preferably, the organic solvent is selected from at least one of toluene, xylene, diethyl ether, deuterated chloroform, tetrahydrofuran, 1,4-dioxane, acetonitrile, or N,N-dimethylformamide; more preferably, the organic solvent is selected from at least one of toluene, xylene, deuterated chloroform, or acetonitrile; the molar ratio of the organic solvent to the active deuterium substrate is 5 to 50:1.

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