A method for synthesizing an aromatic aldehyde compound or a deuterated aromatic aldehyde compound

Abstract

The application discloses a synthesis method of aromatic aldehyde compounds or deuterated aromatic aldehyde compounds, which comprises the following steps: mixing a compound shown in formula I, a manganese catalyst, an alkaline substance, a nitrogen-containing ligand and a solvent, introducing CO, and reacting under heating to obtain the aromatic aldehyde compounds, wherein the manganese catalyst is a manganese (I) compound, a structural formula of the aromatic aldehyde compounds is shown in formula II: ring A is a five-membered or six-membered ring with aromaticity, a substituent R includes at least one of a hydrocarbon group, a halogen, a substituted hydrocarbon group, an alkoxy group, a carbonyl group, an ester group, a nitro group and a cyano group, or the substituent R and the ring A form a fused ring or a fused heterocycle, and X is a halogen. If the deuterated aromatic aldehyde compounds are prepared, a deuterium source reagent needs to be further added in the raw material. The manganese catalyst is used to prepare the aromatic aldehyde compounds, the catalyst is widely sourced, low in cost, simple in steps, strong in operability and easy to realize industrial large-scale production, and the method is good in universality and wide in application prospect.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for synthesizing aromatic aldehydes or deuterated aromatic aldehydes. Background Technology

[0002] Hydroformylation / carboformylation is one of the most commonly used large-scale homogeneous catalytic reactions in the chemical industry today, efficiently converting olefins, hydrogen, and carbon monoxide into aldehydes and related chemicals, with an annual output exceeding 12 million tons. Besides using ethylene as a feedstock, hydroformylation generally produces two types of products: linear and branched products. Historically, the first hydroformylation catalyst was cobalt-coated HCo(CO)₄, accidentally discovered in 1938 by Otto Roelen of Ruhrchemie in Germany. Using this catalyst requires high pressure; the CO partial pressure must increase sharply with increasing temperature to suppress catalyst decomposition (Roelen, O. German Patent DE 849548, 1938 / 1952). Currently, only cobalt and rhodium are used in industrial hydroformylation production. In the early 1980s, rhodium catalysts, with activity hundreds of times higher than cobalt catalysts, were introduced. The rhodium-phosphine catalyst HRh(CO)(PPh₃)₂, which later became the industry standard, not only has high activity but can also operate at relatively low pressures. However, the use of this catalyst also has drawbacks. Besides the high cost and low reserves of rhodium metal, the triphenylphosphine (PPh3) ligand readily dissociates from cobalt metal, requiring an excess of PPh3 to maintain catalyst performance. Nevertheless, the direct reaction products of hydroformylation can be further converted into a series of high-value-added chemicals such as alcohols, acids, esters, and Aldol condensation products. These chemicals are the main raw materials for generating various detergents, surfactants, and high-value-added fine chemicals such as pharmaceuticals and fragrances. Therefore, hydroformylation has developed into one of the most important and largest-scale industrial homogeneous catalytic reactions to date, with global annual production of carbonyl chemical products such as aldehydes and alcohols via hydroformylation exceeding ten million tons. Currently, mature industrial catalytic systems for hydroformylation are all developed and applied by foreign chemical giants such as Ruhrchemie, Shell, Dow, BASF, Exxon, and Esatman. The vast majority of advanced hydroformylation processes use HRh(CO)(PPh3)2 as a catalyst, while cobalt catalysts are rarely used due to their lower activity, large catalyst dosage, and numerous byproducts (Chem. Rev. 2012, 112, 5675). my country heavily relies on imports for some important hydroformylation chemical products, such as higher alcohols. Therefore, developing novel and efficient hydroformylation catalytic systems is of significant strategic importance in breaking the monopoly of foreign patents at its source.

[0003] Manganese is the third most abundant transition metal in the Earth's crust, possessing advantages such as abundant source, low price, environmental friendliness, and diverse oxidation states. Therefore, developing novel hydroformylation catalysts based on inexpensive manganese is an ideal choice. Novel manganese-based catalytic systems may exhibit unique reaction chemistry different from other transition metals. However, manganese-catalyzed hydroformylation reactions have been rarely reported, and the reactivity of HMn(CO)5 is only 10 times that of HCo(CO)5. -4 Therefore, finding new manganese catalysts for deuteration / hydroformylation would be of great significance.

[0004] In addition, deuterated compounds are an important class of high-value-added chemicals. Besides being used as solvents in nuclear magnetic resonance spectroscopy, they also have important applications in exploring drug metabolism, revealing organic reaction mechanisms, and improving material properties. However, there are still some bottlenecks in the synthesis of deuterated compounds: (1) Chemical deuteration synthesis methods generally involve many steps and have low deuteration yields. Furthermore, the transfer of deuterated labeling sites and deuteration phenomena are prone to occur in subsequent reactions, and the research lacks systematicity; (2) Transition metal-catalyzed hydrogen-deuterium exchange methods have mild conditions, but they depend on the chemical environment of carbon-hydrogen bonds and are mainly for the deuteration of alkenes, lacking universality. These factors severely restrict the development and application of deuterium chemistry. Therefore, it is particularly important to utilize manganese catalysts to catalyze the deuteration / hydroformylation reaction to synthesize aryl deuterated aldehydes and carry out subsequent chemical transformations. Summary of the Invention

[0005] This invention aims to solve at least one of the technical problems existing in the prior art. To this end, this invention proposes a method for synthesizing aromatic aldehydes or deuterated aromatic aldehydes, which can prepare the target product using widely available and inexpensive catalysts.

[0006] According to one aspect of the present invention, a method for synthesizing aromatic aldehyde compounds is provided, comprising the following steps:

[0007] The compound shown in Formula I, a manganese catalyst, a basic substance, a nitrogen-containing ligand, and a solvent are mixed, CO is introduced, and the mixture is heated to react, thereby obtaining the product. The manganese catalyst is a manganese (I) compound, and the aromatic aldehyde compound has the structural formula shown in Formula II.

[0008] In the formula, ring A is an aromatic five- or six-membered ring, substituent R includes at least one of hydrocarbon group, halogen, substituted hydrocarbon group, alkoxy group, carbonyl group, ester group, nitro group and cyano group, or substituent R forms a fused ring or fused hetero ring with ring A, and X is a halogen; preferably, the substituted hydrocarbon group is a haloalkyl group; more preferably, the substituted hydrocarbon group is a trifluoromethyl group.

[0009] According to a preferred embodiment of the present invention, at least the following beneficial effects are achieved: aromatic aldehydes can be prepared using halogen-containing aromatic compounds, CO, etc., as raw materials and manganese catalyst. The catalyst is widely available, inexpensive, simple to operate, highly operable, and easy to achieve large-scale industrial production. The method has good universality, and aromatic aldehydes with various substituents can be prepared through the scheme of the present invention, which has broad application prospects.

[0010] In some embodiments of the present invention, X and the halogen in the substituent R are independently selected from F, Cl, Br, or I. When R is a halogen, R may be the same as or different from X.

[0011] In some preferred embodiments of the present invention, the manganese catalyst is selected from manganese compounds containing carbonyl groups.

[0012] In some preferred embodiments of the present invention, the manganese catalyst is selected from manganese compounds with a pincer-like structure.

[0013] In some embodiments of the present invention, the manganese catalyst is selected from at least one of manganese pentacarbonyl bromide, manganese tricarbonylcyclopentadiene, MnCl, MnBr, and MnI. Both organic and inorganic manganese compounds are acceptable, but manganese pentacarbonyl bromide and manganese tricarbonylcyclopentadiene are more preferred.

[0014] In some embodiments of the present invention, the alkaline substance is selected from strong base-weak acid salts. Compared with organic bases such as pyridine, triethylamine, and 4-p-dimethylaminopyridine, using strong base-weak acid salts can achieve higher yields.

[0015] In some preferred embodiments of the present invention, the alkaline substance is selected from at least one of carbonates, bicarbonates, or acetates. Examples include cesium carbonate, potassium carbonate, sodium carbonate, sodium bicarbonate, sodium acetate, and potassium acetate.

[0016] In some more preferred embodiments of the present invention, the alkaline substance is selected from at least one of cesium carbonate, potassium carbonate, sodium carbonate, sodium bicarbonate, sodium acetate, and potassium acetate.

[0017] In some embodiments of the present invention, the solvent is selected from at least one of ether solvents, aromatic hydrocarbons, or haloalkanes. Using ether solvents, aromatic hydrocarbons, or haloalkanes is more effective than using esters, alcohols, or solvents containing carbon-oxygen or sulfur-oxygen double bonds.

[0018] In some embodiments of the present invention, the solvent is selected from at least one of THF, 1,4-dioxane, toluene, and dichloroethane.

[0019] In some embodiments of the present invention, the nitrogen-containing ligand is selected from ligands containing both nitrogen and phosphine; preferably, it is an NNP-type ligand.

[0020] In some embodiments of the present invention, the nitrogen-containing ligand is selected from one of the following structural formulas:

[0021]

[0022] In some embodiments of the present invention, the nitrogen-containing ligand is selected from one of the following structural formulas:

[0023]

[0024] In some embodiments of the present invention, the heating temperature is 60–100°C; preferably 80°C. The reaction can occur when heated to below 100°C, and the reaction conditions are relatively mild.

[0025] In some embodiments of the present invention, the reaction time is 18 to 30 hours; preferably 24 hours.

[0026] In some preferred embodiments of the present invention, the aromatic aldehyde compound is selected from at least one of the following compounds: 4-methoxybenzaldehyde, 4-methylbenzaldehyde, 4-halobenzaldehyde, piperaldehyde, 3-benzofuranaldehyde, 1-naphthaldehyde, and 1,1'-biphenyl-4-carboxaldehyde.

[0027] According to another aspect of the present invention, a method for synthesizing deuterated aromatic aldehydes is provided, comprising the following steps:

[0028] The compound shown in Formula I, a manganese catalyst, a basic substance, a nitrogen-containing ligand, a deuterium source reagent, and a solvent are mixed, CO is introduced, and the reaction is carried out under heating to obtain the product. The manganese catalyst includes a pincer-type manganese catalyst containing a carbonyl group. The structural formula of the deuterated aromatic aldehyde compound is shown in Formula III.

[0029] In the formula, ring A is an aromatic five- or six-membered ring, substituent R includes at least one of hydrocarbon group, halogen, substituted hydrocarbon group, alkoxy group, carbonyl group, ester group, nitro group and cyano group, or substituent R forms a fused ring or fused hetero ring with ring A, and X is a halogen; preferably, the substituted hydrocarbon group is a haloalkyl group; more preferably, the substituted hydrocarbon group is a trifluoromethyl group.

[0030] According to a preferred embodiment of the present invention, at least the following beneficial effects are achieved: aromatic aldehydes can be prepared using halogen-containing aromatic compounds, CO, etc., as raw materials and manganese catalysts. The catalysts are widely available, inexpensive, simple in procedure, highly operable, and easy to implement for large-scale industrial production; the method has good universality, and deuterated aromatic aldehydes with various substituents can be prepared through the scheme of the present invention, which has broad application prospects; the deuterated aromatic aldehydes prepared by the scheme of the present invention have a high deuteration rate.

[0031] In some embodiments of the present invention, X and the halogen in the substituent R are independently selected from F, Cl, Br, or I. When R is a halogen, R may be the same as or different from X.

[0032] In some preferred embodiments of the present invention, the manganese catalyst is selected from manganese compounds containing carbonyl groups.

[0033] In some preferred embodiments of the present invention, the manganese catalyst is selected from manganese compounds with a pincer-like structure.

[0034] In some embodiments of the present invention, the manganese catalyst is selected from at least one of manganese pentacarbonyl bromide, manganese tricarbonylcyclopentadiene, MnCl, MnBr, and MnI. Both organic and inorganic manganese compounds are acceptable, with manganese pentacarbonyl bromide and manganese tricarbonylcyclopentadiene being more preferred. In some embodiments of the present invention, the basic substance is selected from strong base-weak acid salts. Compared to organic bases such as pyridine, triethylamine, and 4-p-dimethylaminopyridine, using strong base-weak acid salts can achieve higher yields.

[0035] In some preferred embodiments of the present invention, the alkaline substance is selected from at least one of carbonates, bicarbonates, or acetates. Examples include cesium carbonate, potassium carbonate, sodium carbonate, sodium bicarbonate, sodium acetate, and potassium acetate.

[0036] In some more preferred embodiments of the present invention, the alkaline substance is selected from at least one of cesium carbonate, potassium carbonate, sodium carbonate, sodium bicarbonate, sodium acetate, and potassium acetate.

[0037] In some embodiments of the present invention, the deuterium source reagent includes heavy water.

[0038] In some embodiments of the present invention, the solvent is selected from at least one of ether solvents, aromatic hydrocarbons, or haloalkanes. Using ether solvents, aromatic hydrocarbons, or haloalkanes is more effective than using esters, alcohols, or solvents containing carbon-oxygen or sulfur-oxygen double bonds.

[0039] In some embodiments of the present invention, the solvent is selected from at least one of ether solvents containing 2 to 6 carbons, aromatic hydrocarbons containing phenyl groups, and chloroalkanes.

[0040] In some embodiments of the present invention, the solvent is selected from at least one of THF, 1,4-dioxane, toluene, and dichloroethane.

[0041] In some embodiments of the present invention, the nitrogen-containing ligand is selected from ligands containing both nitrogen and phosphine; preferably, it is an NNP-type ligand.

[0042] In some embodiments of the present invention, the nitrogen-containing ligand is selected from one of the following structural formulas:

[0043]

[0044] In some embodiments of the present invention, the nitrogen-containing ligand is selected from one of the following structural formulas:

[0045]

[0046] In some embodiments of the present invention, the heating temperature is 60–100°C; preferably 80°C. The reaction can occur when heated to below 100°C, and the reaction conditions are relatively mild.

[0047] In some embodiments of the present invention, the reaction time is 18 to 30 hours; preferably 24 hours.

[0048] In some preferred embodiments of the present invention, the deuterated aromatic aldehyde compound is selected from at least one of the following compounds: 4-methoxybenzaldehyde-α-d 1 4-Methylbenzaldehyde-α-d 1 4-Halobenzaldehyde-α-d 1 Piperaldehyde-α-d 1 3-Benzofuranaldehyde-α-d 1 1-Naphthaldehyde-α-d 1 1,1'-Biphenyl-4-formaldehyde-α-d 1 .

[0049] As used in this specification and in the claims, "a five- or six-membered aromatic ring" refers to an aromatic ring consisting of a five- or six-membered aromatic ring or a heteroaromatic ring, such as a benzene ring, a furan ring, a thiophene ring, a pyrrole ring, a thiazole ring, an imidazole ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, etc.

[0050] As used in this specification and in the claims, "alkyl" includes alkyl and aromatic groups. The term "alkyl" refers to a saturated straight-chain or branched aliphatic hydrocarbon group. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, and hexadecyl, preferably alkyl groups with 1 to 6 carbon atoms. The term "aromatic" represents an aromatic hydrocarbon group comprising one or more phenyl groups, preferably aromatic hydrocarbon groups with 6 to 10 carbon atoms, more preferably phenyl.

[0051] As used in this specification and in the claims, "alkoxy" refers to a group of the formula "-O-alkyl", including but not limited to methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, preferably alkoxy with 1 to 6 carbon atoms.

[0052] As used in this specification and in the claims, "substitution" means that a group may be further substituted by one or more groups selected from the following: alkyl, alkenyl, alkynyl, aryl, halogen, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, hydroxyl, alkoxy, alkenyloxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, heteroaryl, nitro, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroheterocyclic, amino, alkylamino, dialkylamino, alkenylamino, alkynylamino, arylamino, diarylamino, phenylamino, diphenylamino, benzylamino, dibenzylamino, hydrazyl, acyl, acylamino, diacylamino, acyloxy, heterocyclic, heterocyclic oxy, heterocyclic amino, haloheterocyclic, carboxyl ester, carboxyl, carboxylamide, mercapto, alkylthio, benzylthio, acylthio, and phosphorus-containing groups. Preferably, the substituted hydrocarbon group is a haloalkyl group.

[0053] As used in this specification and in the claims, "compound" means all stereoisomers, geometric isomers, tautomers, and isotopes including the described structure. Unless otherwise stated, compounds identified herein as a particular tautomer by name or structure are intended to include other tautomers. It should be understood that some compounds provided herein may contain one or more asymmetric centers and can therefore be prepared and isolated as mixtures of isomers, such as racemic mixtures, or in enantiomeric purity.

[0054] As used in this specification and in the claims, "tautomer" means a compound whose structure is significantly different in atomic arrangement but exists in a simple and rapid equilibrium, and it should be understood that the compounds provided herein can be described as different tautomers, and when a compound has a tautomer form, all tautomer forms are within the scope of this invention, and the naming of the compound does not exclude any tautomer.

[0055] As used in this specification and in the claims, "manganese(I) compound" means that the manganese in the compound has a valence of +1.

[0056] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Attached Figure Description

[0057] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:

[0058] Figure 1 This is the product obtained in Embodiment 1 of the present invention. 1 Figure of HNMR characterization results.

[0059] Figure 2 This is the product obtained in Embodiment 1 of the present invention. 13 CNMR characterization results diagram.

[0060] Figure 3 This is the product obtained in Embodiment 2 of the present invention. 1 Figure of HNMR characterization results.

[0061] Figure 4 This is the product obtained in Embodiment 2 of the present invention. 13 CNMR characterization results diagram. Detailed Implementation

[0062] The following will clearly and completely describe the concept and technical effects of the present invention in conjunction with embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention. Unless otherwise specified, the experimental methods used in the embodiments are conventional methods; the materials and reagents used, unless otherwise specified, are commercially available. Unless otherwise specified, the same parameter value is the same in all embodiments. The embodiments described below are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0063] The term "room temperature" as used in this invention refers to any temperature between 25 and 5°C, and specifically 25°C in the embodiments.

[0064] Example 1

[0065] This example prepared 4-methoxybenzaldehyde-α-d 1 The preparation route is as follows:

[0066]

[0067] The specific process is as follows:

[0068] In a 25 mL reaction tube, p-methoxybromobenzene (93 mg, 0.5 mmol), manganese pentacarbonyl bromide (10 mol%), heavy water (2.0 mmol), and NNP-type ligand L1 (20 mol%) were added, along with cesium carbonate (163 mg, 0.5 mmol) as a basic agent and tetrahydrofuran (Solvent, 2 mL) as a solvent. CO (1 atm) was then introduced, and the reaction was stirred at 80 °C for 24 h. After the reaction was complete, the temperature was lowered to room temperature, and the reaction was quenched with ethyl acetate. The mixture was then washed with saturated brine, and the organic phase was separated. The aqueous phase was repeatedly extracted three times with ethyl acetate, and the combined organic phases were dried over anhydrous sodium sulfate. The solvent was removed by vacuum distillation, followed by column chromatography to obtain a pale yellow liquid (58.3 mg, 85% yield). Nuclear magnetic resonance (NMR) analysis of the pale yellow liquid after the reaction showed a deuteration rate of 95%.

[0069] The product of this embodiment 1 The H NMR characterization results are as follows: Figure 1 As shown, 13 The C NMR characterization results are as follows: Figure 2 As shown. The NMR characterization data are as follows:

[0070] Pale yellow liquid (yield: 85%, deuteration rate: 96%); 1 H NMR (400MHz, CDCl3) δ9.87 (s, 0.04H), 7.83 (dt, J = 8.8, 2.4Hz, 2H), 6.99 (dt, J = 8.8, 2.4Hz, 2H), 3.87 (s, 3H); 13 C NMR (100MHz, CDCl3) δ190.8,164.5,132.0(2C),129.9,114.3(2C),55.5; 2 ¹H NMR (77MHz, CH₂Cl₂) δ 9.88 (s, 1D). Example 2

[0071] This example demonstrates a synthetic method for 4-methoxybenzaldehyde, and the preparation route is as follows:

[0072]

[0073] The specific procedure was as follows: In a 25 mL reaction tube, p-methoxyiodobenzene (118 mg, 0.5 mmol), manganese tricarbonylcyclopentadiene (10 mol%), water (2.0 mmol), and NNP-type ligand L1 (20 mol%) were added, along with cesium carbonate (163 mg, 0.5 mmol) as a base and tetrahydrofuran (Solvent, 2 mL) as a solvent. CO (1 atm) was then introduced, and the reaction was stirred for 24 h at 80 °C. After the reaction was complete, the temperature was lowered to room temperature, and the reaction was quenched with ethyl acetate. The mixture was then washed with saturated brine, and the organic phase was separated. The aqueous phase was repeatedly extracted three times with ethyl acetate, and the organic phases were combined. Anhydrous sodium sulfate was added for drying, and the solvent was removed by vacuum distillation. The mixture was then separated by column chromatography, yielding a pale yellow liquid (56.4 mg, 83% yield).

[0074] The product of this embodiment 1 The H NMR characterization results are as follows: Figure 3 As shown, 13 The C NMR characterization results are as follows: Figure 4 As shown. The NMR characterization data are as follows:

[0075] 1 H NMR (400MHz, CDCl3) δ9.87 (s, 1H), 7.82 (d, J = 8.8Hz, 2H), 6.99 (d, J = 8.8Hz, 2H), 3.87 (s, 3H); 13 C NMR (100MHz, CDCl3) δ190.7,164.5,131.9(2C),129.9,114.2(2C),55.5.

[0076] Example 3

[0077] This example prepared 4-methylbenzaldehyde-α-d 1 Its preparation route and process are basically the same as in Example 1, except that the raw material is p-bromotoluene.

[0078] The characterization data of the product in this embodiment are as follows:

[0079] Pale yellow liquid (yield: 88%, deuteration rate: 93%); 1 H NMR (400MHz, CDCl3) δ9.95 (s, 0.07H), 7.78 (d, J = 8.1Hz, 2H), 7.33 (dd, J = 7.9Hz, 2H), 2.44 (s, 3H); 13 C NMR (100MHz, CDCl3) δ191.7,145.6,134.1,129.9,129.7,21.9; 2H NMR(77MHz,CH2Cl2)δ9.95(s,1D).

[0080] Example 4

[0081] This example prepared 4-chlorobenzaldehyde-α-d 1 Its preparation route and process are basically the same as in Example 1, except that the raw material is p-bromochlorobenzene.

[0082] The characterization data of the product in this embodiment are as follows:

[0083] Pale yellow liquid (yield: 89%, deuteration rate: 97%); 1 H NMR (400MHz, CDCl3): δ9.96 (s, 0.03H), 7.82 (d, J = 8.6Hz, 2H), 7.50 (d, J = 8.6Hz, 2H); 13 C NMR (100MHz, CDCl3): δ190.5,141.0,134.5,130.8,129.4; 2 H NMR(77MHz,CH2Cl2)δ10.02(s,1D).

[0084] Example 5

[0085] This example prepared 4-fluorobenzaldehyde-α-d 1 Its preparation route and process are basically the same as in Example 1, except that the raw material is p-bromofluorobenzene.

[0086] The characterization data of the product in this embodiment are as follows:

[0087] Pale yellow liquid (yield: 86%, deuteration rate: 96%); 1 H NMR (400MHz, CDCl3) δ9.89 (s, 0.04H), 7.87-7.83 (m, 2H), 7.14 (t, J = 8.6Hz, 2H); 13 C NMR (100MHz, CDCl3) δ190.1, 166.5 (d, J = 256.6Hz), 132.8 (t, J = 3.4Hz), 132.3 (d, J = 9.6Hz), 116.3 (d, J = 22.3Hz); 2 H NMR(77MHz,CH2Cl2)δ9.95(s,1D).

[0088] Example 6

[0089] This example prepared 4-trifluoromethylbenzaldehyde-α-d 1 Its preparation route and process are basically the same as in Example 1, except that the raw material is p-trifluoromethylbromobenzene.

[0090] The characterization data of the product in this embodiment are as follows:

[0091] Pale yellow liquid (yield: 81%, deuteration rate: 95%); 1 H NMR (400MHz, CDCl3) δ10.08 (s, 0.05H), 8.00 (d, J = 8.0Hz, 2H), 7.79 (d, J = 8.0Hz, 2H); 13 C NMR (100MHz, CDCl3) δ190.7, 138.5, 135.4 (q, J = 32.6Hz), 129.8, 126.0 (q, J = 3.8Hz), 123.3 (d, J = 273Hz); 2 H NMR(77MHz,CH2Cl2)δ10.15(s,1D).

[0092] Example 7

[0093] This example prepared piperonal-α-d 1 Its preparation route and process are basically the same as in Example 1, except that the raw material is 4-bromo-1,2-methylenedioxybenzene.

[0094] The characterization data of the product in this embodiment are as follows:

[0095] Pale yellow liquid (yield: 83%, deuteration rate: 93%); 1 H NMR (400MHz, CDCl3) δ9.77(s,0.07H),7.38(dd,J=7.9,1.5Hz,1H),7.30(d,J=1.5Hz,1H),6.91(d,J=7.9Hz,1H),6.05(s,2H); 13 C NMR (100MHz, CDCl3) δ190.0,153.0,148.6,131.7,128.6,108.3,106.8,102.0; 2 H NMR(77MHz,CH2Cl2)δ9.82(s,1D).

[0096] Example 8

[0097] This example prepared 3-benzofuranaldehyde-α-d 1 Its preparation route and process are basically the same as in Example 1, the difference being: the raw material is

[0098] The characterization data of the product in this embodiment are as follows:

[0099] Pale yellow liquid (yield: 78%, deuteration rate: 92%); 1H NMR (400MHz, CDCl3) δ10.156(s,0.08H),8.27(s,1H),8.25-8.17(m,1H),7.59-7.53(m,1H),7.44-7.36(m,2H); 13 C NMR (100MHz, CDCl3) δ184.5,156.0,155.4,126.3,124.9,123.6,122.9,122.6,111.7; 2 H NMR(77MHz,CH2Cl2)δ10.20(s,1D).

[0100] Example 9

[0101] This example prepared 1-naphthaldehyde-α-d 1 Its preparation route and process are basically the same as in Example 1, except that the raw material is 1-bromonaphthalene.

[0102] The characterization data of the product in this embodiment are as follows:

[0103] White solid (yield: 86%, deuteration rate: 96%); 1 H NMR (400MHz, CDCl3) δ10.26 (s, 0.04H), 9.21 (d, J = 8.6Hz, 1H), 7.93 (d, J = 8.2Hz, 1H), 7.85-7.81 (m, 2H), 7.64-7.58 (m, 1H), 7.52-7.43 (m, 2H); 13 C NMR (100MHz, CDCl3) δ193.2,136.7,135.2,133.7,131.4-131.1(m),130.4,129.0,128.5,126.9,124.9; 2 H NMR(77MHz,CH2Cl2)δ10.30(s,1D).

[0104] Example 10

[0105] This example prepared [1,1'-Biphenyl]-4-carbaldehyde-α-d 1 Its preparation route and process are basically the same as in Example 1, except that the raw material is 4-bromobiphenyl.

[0106] The characterization data of the product in this embodiment are as follows:

[0107] Yellow solid (yield: 87%, deuteration rate: 94%); 1H NMR (400MHz, CDCl3) δ10.05 (s, 0.06H), 7.956 (d, J = 8.1Hz, 2H), 7.74 (d, J = 8.1Hz, 2H), 7.63 (d, J = 7.5Hz, 2H), 7.48 (t, J = 7.4Hz, 2H), 7.47-7.42 (m, 1H); 13 C NMR (100MHz, CDCl3) δ191.6,147.2,139.6,135.1,130.2,129.2,128.4,127.6,127.3; 2 H NMR(77MHz,CH2Cl2)δ10.11(s,1D).

[0108] Example 11

[0109] This example prepared 4-methoxybenzaldehyde-α-d 1 The difference between this example and Example 1 is that the ligand is different; the ligand used is... Separation was performed by column chromatography, yielding a pale yellow liquid (52.1 mg, 76% yield). After the reaction was complete, the pale yellow liquid was analyzed by nuclear magnetic resonance (NMR), showing a deuteration rate of 93%.

[0110] Example 12

[0111] This example prepared 4-methoxybenzaldehyde-α-d 1 The difference between this example and Example 1 is that the ligand is different; the ligand used is... After separation by column chromatography, a small amount of light yellow liquid was obtained (separation yield less than 5%).

[0112] Example 13

[0113] This example prepared 4-methoxybenzaldehyde-α-d 1 The difference between this example and Example 1 is that the ligand is different; the ligand used is...

[0114] Separation was performed by column chromatography, yielding a pale yellow liquid (59.7 mg, separation yield 87%). After the reaction was complete, the pale yellow liquid was analyzed by nuclear magnetic resonance (NMR), and the deuteration rate was 95%.

[0115] Example 14

[0116] This example prepared 4-methoxybenzaldehyde-α-d 1 The difference between this example and Example 1 is that the ligand is different; the ligand used is...

[0117] Separation was performed by column chromatography, yielding a pale yellow liquid (57.6 mg, separation yield 84%). After the reaction was complete, the pale yellow liquid was analyzed by nuclear magnetic resonance (NMR), and the deuteration rate was 96%.

[0118] Example 15

[0119] This example prepared 4-methoxybenzaldehyde-α-d 1 The difference between this example and Example 1 is that the ligand is different; the ligand used is...

[0120] After separation by column chromatography, a small amount of light yellow liquid was obtained (separation yield less than 5%).

[0121] Example 16

[0122] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the type of alkaline substance used is different; potassium carbonate was used instead. The yield of the prepared product was measured, and the results were comparable to those of Example 2; the structure was also measured, and the results were consistent with those of Example 2.

[0123] Example 17

[0124] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the type of alkaline substance used is different; sodium carbonate was used instead. The yield of the obtained product was measured, and the results were comparable to those of Example 2; the structure was also measured, and the results were consistent with those of Example 2.

[0125] Example 18

[0126] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the type of alkaline substance used is different; sodium bicarbonate was used instead. The yield of the prepared product was measured, and the results were comparable to those of Example 2; the structure was also measured, and the results were consistent with those of Example 2.

[0127] Example 19

[0128] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the type of alkaline substance used is different; sodium acetate was used instead. The yield of the prepared product was measured, and the results were comparable to those of Example 2; the structure was also measured, and the results were consistent with those of Example 2.

[0129] Example 20

[0130] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the type of alkaline substance used is different; potassium acetate was used instead. The yield of the prepared product was measured, and the results were comparable to those of Example 2; the structure was also measured, and the results were consistent with those of Example 2.

[0131] Example 21

[0132] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the solvent used is different; THF was used. The yield of the obtained product was measured, and the results were comparable to those of Example 2; the structure was also determined, and the results were consistent with those of Example 2.

[0133] Example 22

[0134] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the solvent used is different: 1,4-dioxane was used. The yield of the prepared product was measured, and the results were comparable to those of Example 2; the structure was also measured, and the results were consistent with those of Example 2.

[0135] Example 23

[0136] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the solvent used is toluene. The yield of the product was measured, and the results were comparable to those of Example 2; the structure was also determined, and the results were consistent with those of Example 2.

[0137] Example 24

[0138] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the solvent used is different; dichloromethane was used. The yield of the obtained product was measured, and the results were comparable to those of Example 2; the structure was also measured, and the results were consistent with those of Example 2.

[0139] Example 25

[0140] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the solvent used is different; DMSO was used, and the yield was 20%.

[0141] Example 26

[0142] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the solvent used is DMF, and the yield is 18%.

[0143] Example 27

[0144] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the solvent used is different; DMAc was used, and the yield was 23%.

[0145] Example 28

[0146] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the solvent used is ethyl acetate, and the yield is 8%.

[0147] Example 29

[0148] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the solvent used is methanol, and the yield is 12%.

[0149] Example 30

[0150] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the type of alkaline substance used is different; the alkaline substance used is pyridine, and the yield is 9%.

[0151] Example 31

[0152] This example prepared 4-methoxybenzaldehyde, which differs from Example 2 in that the type of alkaline substance used is different; the alkaline substance used is triethylamine, and the yield is 35%.

[0153] Example 32

[0154] In this example, 4-methoxybenzaldehyde was prepared. The difference between this example and Example 2 is that the type of alkaline substance used is different. The alkaline substance used is 4-p-dimethylaminopyridine, and the yield is 13%.

[0155] The embodiments of the present invention have been described in detail above, but the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention.

Claims

1. A method for synthesizing aromatic aldehyde compounds, characterized in that: Includes the following steps: The compound shown in Formula I, a manganese catalyst, a basic substance, a nitrogen-containing ligand, and a solvent are mixed, CO is introduced, and the mixture is heated to react, thereby obtaining the product. The manganese catalyst is a manganese (I) compound, and the aromatic aldehyde compound has the structural formula shown in Formula II. In the formula, ring A is an aromatic five- or six-membered ring, substituent R is at least one of a hydrocarbon group, halogen, substituted hydrocarbon group, alkoxy group, carbonyl group, ester group, nitro group, and cyano group, or substituent R forms a fused ring or fused heterocyclic ring with ring A, and X is a halogen; the manganese (I) compound is selected from manganese compounds containing a carbonyl group; the basic substance is selected from strong base weak acid salts; the solvent is selected from ether solvents, aromatic hydrocarbons, or haloalkanes; the nitrogen-containing ligand is selected from one of the following structural formulas:

2. The method for synthesizing aromatic aldehydes according to claim 1, characterized in that: The substituted hydrocarbon group is a haloalkyl group.

3. The method for synthesizing aromatic aldehydes according to claim 1, characterized in that: The substituted hydrocarbon group is trifluoromethyl.

4. The method for synthesizing aromatic aldehydes according to claim 1, characterized in that: The aromatic aldehydes are selected from at least one of the following compounds: 4-methoxybenzaldehyde, 4-methylbenzaldehyde, 4-halobenzaldehyde, piperaldehyde, 3-benzofuranaldehyde, 1-naphthaldehyde, and 1,1'-biphenyl-4-carboxaldehyde.

5. A method for synthesizing deuterated aromatic aldehydes, characterized in that: Includes the following steps: The compound shown in Formula I, a manganese catalyst, a basic substance, a nitrogen-containing ligand, a deuterium source reagent, and a solvent are mixed, CO is introduced, and the reaction is carried out under heating to obtain the product. The manganese catalyst is a manganese (I) compound, and the structural formula of the deuterated aromatic aldehyde compound is shown in Formula III. In the formula, ring A is an aromatic five- or six-membered ring, substituent R is at least one of a hydrocarbon group, halogen, substituted hydrocarbon group, alkoxy group, carbonyl group, ester group, nitro group, and cyano group, or substituent R forms a fused ring or fused heterocyclic ring with ring A, and X is a halogen; the manganese (I) compound is selected from manganese compounds containing a carbonyl group; the basic substance is selected from strong base weak acid salts; the solvent is selected from ether solvents, aromatic hydrocarbons, or haloalkanes; the nitrogen-containing ligand is selected from one of the following structural formulas:

6. The method for synthesizing deuterated aromatic aldehydes according to claim 5, characterized in that: The substituted hydrocarbon group is a haloalkyl group.

7. The method for synthesizing deuterated aromatic aldehydes according to claim 5, characterized in that: The substituted hydrocarbon group is trifluoromethyl.

8. The method for synthesizing deuterated aromatic aldehydes according to claim 5, characterized in that: The deuterium source reagent includes heavy water.

9. The method for synthesizing deuterated aromatic aldehydes according to claim 5, characterized in that: The deuterated aromatic aldehyde compound is selected from at least one of the following compounds: 4-methoxybenzaldehyde-α-d 1 4-Methylbenzaldehyde-α-d 1 4-Halobenzaldehyde-α-d 1 Piperaldehyde-α-d 1 3-Benzofuranaldehyde-α-d 1 1-Naphthaldehyde-α-d 1 1,1'-Biphenyl-4-formaldehyde-α-d 1 .

10. The method for synthesizing aromatic aldehydes according to claim 1 or the method for synthesizing deuterated aromatic aldehydes according to claim 5, characterized in that: The aromatic five- or six-membered ring includes a benzene ring, a furan ring, a thiophene ring, a pyrrole ring, a thiazole ring, an imidazole ring, a pyridine ring, a pyrimidine ring, a pyrazine ring; and / or, the hydrocarbon group is an alkyl or an aromatic group.

11. The method for synthesizing aromatic aldehydes according to any one of claims 1 to 4 or the method for synthesizing deuterated aromatic aldehydes according to any one of claims 5 to 9, characterized in that: The manganese catalyst is selected from manganese compounds containing carbonyl groups and having a pincer-like structure.

12. The method for synthesizing aromatic aldehydes according to any one of claims 1 to 4 or the method for synthesizing deuterated aromatic aldehydes according to any one of claims 5 to 9, characterized in that: The manganese catalyst is selected from at least one of manganese pentacarbonyl bromide and manganese tricarbonylcyclopentadiene; the alkaline substance is selected from at least one of carbonate, bicarbonate or acetate; and / or the solvent is selected from at least one of ether solvents containing 2 to 6 carbons, aromatic hydrocarbons containing phenyl groups, and chloroalkanes.

13. The method for synthesizing aromatic aldehydes according to any one of claims 1 to 4 or the method for synthesizing deuterated aromatic aldehydes according to any one of claims 5 to 9, characterized in that: The alkaline substance is selected from at least one of cesium carbonate, potassium carbonate, sodium carbonate, sodium bicarbonate, sodium acetate, and potassium acetate; and / or the solvent is selected from at least one of THF, 1,4-dioxane, toluene, and dichloroethane.

14. The method for synthesizing aromatic aldehydes according to any one of claims 1 to 4 or the method for synthesizing deuterated aromatic aldehydes according to any one of claims 5 to 9, characterized in that: The heating temperature is 60–100°C; and / or the reaction time is 18–30 h.

15. The method for synthesizing aromatic aldehydes according to any one of claims 1 to 4 or the method for synthesizing deuterated aromatic aldehydes according to any one of claims 5 to 9, characterized in that: The heating temperature is 80°C; and / or the reaction time is 24 hours.

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