A method for synthesizing C-1 deuterated aromatic aldehyde catalyzed by palladium

Abstract

The invention discloses a method for synthesizing C-1 deuterated aromatic aldehydes by palladium-catalyzed aryl sulfide salt compounds, and belongs to the field of organic deuterated compound synthesis. The present invention uses aryl sulfide salt compounds, sodium deuterate formate and carbon monoxide as raw materials, palladium salt as catalyst, tri(1-naphthyl)phosphine as ligand, adds triethylamine, reacts at 120 DEG C in N, N-dimethylformamide solvent for 12 hours, and obtains C-1 deuterated aromatic aldehyde compounds after the reaction ends. The synthetic method of the present invention, substrate and deuterated reagent are cheap and easy to obtain, reaction efficiency is high, deuteration rate is high, adaptability of functional group is very good, and reaction conditions are simple to operate, with good industrial application prospects.

Description

Technical Field

[0001] The invention belongs to the field of synthesis of organic deuterated compounds, and in particular relates to a method for synthesizing a C-1 deuterated aromatic aldehyde using palladium catalysis. Background Art

[0002] Deuterium substitution technology has a great impact on the fields of pharmacy, material science, biochemistry, and experimental testing. In 2017, Austedo, developed by TEVA, became the first deuterated drug approved by the US Food and Drug Administration. Therefore, the synthesis of deuterated compounds has attracted much attention from organic chemists. Aromatic aldehydes are an important class of organic compounds. They are not only important fragments of many biologically active molecules, but also important intermediates for synthetic materials, drugs, and agricultural chemicals.

[0003] In recent years, organic chemists from various countries have devoted themselves to the synthesis of C-1 deuterated aromatic aldehydes. The classical methods for generating C-1 deuterated aromatic aldehydes mainly rely on the reduction-(oxidation) reaction of carboxylates or amides with deuterated reducing agents (Angew. Chem. Int. Ed. 2015, 54, 15525, J. Am. Chem. Soc. 2007, 129, 3408-3419); photocatalytic dehydroxydeuteration of benzoic acid (Angew. Chem. Int. Ed. 2019, 58, 312-316); palladium / rhodium co-catalyzed aryl halide aldehyde reaction (Angew. Chem. Int. Ed. 2018, 57, 10362-10367) and free radical-mediated hydrogen / deuterium exchange reaction strategy of aldehyde compounds (Angew. Chem. Int. Ed. 2017, 56, 7808-7812, Nature Catal.2019, 2, 1071-1077, ACS Catal.2021, 11, 14561-14569, Chem 2019, 5, 2484-2494, ACS Catal.2020, 10, 2226-2230, Chem.Sci.2020, 11, 1026-1031, Chem.Sci.2020, 11, 8912-8918). However, these methods are often limited by harsh reaction conditions and thus affect the scope of application of the substrate, and under some conditions, the product deuterated chlorine is low, and the deuterated selectivity is poor. It is difficult to apply to industrial production applications. Therefore, the development of a synthetic C-1 deuterated aromatic aldehyde with easy raw materials, wide substrate application range, high efficiency, high selectivity and high deuteration rate has important practical significance in the synthesis of deuterated chemicals and deuterated drugs. Summary of the invention

[0004] The object of the present invention is to provide a method for synthesizing a palladium-catalyzed C-1 deuterated aromatic aldehyde. The method has low-cost and readily available reaction substrates and deuterated reagents, high reaction efficiency, high deuterated rate, good adaptability of functional groups, simple reaction conditions and operation, and has good industrial application prospects.

[0005] A method for synthesizing a palladium-catalyzed C-1 deuterated aromatic aldehyde, the method comprising the following steps:

[0006] Dispersing an aryl sulfide salt, a deuterated salt, a palladium catalyst, a phosphine ligand, and a base in a solvent and reacting them in a carbon monoxide atmosphere, and obtaining a C-1 deuterated aromatic aldehyde after the reaction is completed;

[0007] The structural formula of the aryl sulfide salt compound is: The deuterated salt is sodium deuterated formate; the structural formula of the C-1 deuterated aromatic aldehyde is:

[0008] Wherein R is a substituted or unsubstituted aromatic ring, a substituted or unsubstituted aromatic heterocycle; substitution includes mono- or di-substitution, and the substituent is selected from: C1-2 alkoxy, halogen (Cl, F), hydroxyl, acetyl, phenyl, C1-6 alkyl, etc.

[0009] In one embodiment of the present invention, the reaction temperature is 120° C. and the reaction time is 12 h.

[0010] In one embodiment of the present invention, the aromatic ring is a benzene ring or a heterocyclic ring.

[0011] In one embodiment of the present invention, the aromatic heterocycle is a 5-membered or 6-membered aromatic heterocycle having at least one heteroatom selected from N and S. Specific options include:

[0012] In one embodiment of the present invention, the method according to claim 1 is characterized in that the molar ratio of the aryl sulfide salt compound to sodium deuterated formate is 1:3, 1:2 or 1:1.5.

[0013] In one embodiment of the present invention, the ligand includes any one or more of the following structures: tri(1-naphthyl)phosphine as a ligand, triphenylphosphine, tri(4-methoxyphenyl)phosphine.

[0014] In one embodiment of the present invention, the amount of the ligand relative to the arylsulfide salt compound is 20 mol%.

[0015] In one embodiment of the present invention, the amount of the palladium salt relative to the aryl sulfide salt compound is 10 mol %.

[0016] In one embodiment of the present invention, the palladium salt is selected from any one or more of the following: PdCl2, PdCl2(PPh3)2, and Pd(OAc)2.

[0017] In one embodiment of the present invention, the alkaline reagent is selected from any one or more of the following: Na2CO3, iPr2NEt and Et3N.

[0018] In one embodiment of the present invention, the molar ratio of the base reagent to the aryl sulfide salt compound is 2:1.

[0019] In one embodiment of the present invention, the organic solvent is acetonitrile, N,N-dimethylformamide or toluene.

[0020] In one embodiment of the present invention, the amount of the organic solvent used is 1 mL / 0.2 mmol of the aryl sulfide compound reagent, that is, 5 mL / mmol of the aryl sulfide compound.

[0021] In one embodiment of the present invention, the reaction is carried out under a carbon monoxide atmosphere.

[0022] In one embodiment of the present invention, the synthetic route of the reaction is as follows:

[0023]

[0024] In one embodiment of the present invention, R is a substituted or unsubstituted aromatic ring, a substituted or unsubstituted aromatic heterocycle; substitution includes one to three substitutions, and the substituents are selected from: C1-2 alkoxy, halogen (Cl, F), hydroxyl, acetyl, phenyl, C1-6 alkyl, etc.

[0025] In one embodiment of the present invention, the aromatic aldehyde compound specifically comprises the following structure:

[0026]

[0027] In one embodiment of the present invention, the method comprises the following specific steps:

[0028] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, PdCl2(PPh3)2, tri(1-naphthyl)phosphine, aryl sulfide compound, sodium deuterated formate, Et3N, solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12 hours. After the reaction was completed, the reaction mixture was filtered through diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the target compound.

[0029] Beneficial effects:

[0030] The invention uses an aryl sulfide salt compound, sodium deuterated formate and carbon monoxide as raw materials, a palladium salt as a catalyst, tri(1-naphthyl)phosphine as a ligand, adds triethylamine, reacts at 120° C. for 12 hours in an N,N-dimethylformamide solvent, and obtains a C-1 deuterated aromatic aldehyde compound after the reaction. The synthesis method of the invention has low-cost and easy-to-obtain substrates and deuterated reagents, high reaction efficiency, high deuteration rate, good adaptability of functional groups, and simple and convenient reaction conditions, and has good industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 The schematic diagram of the synthesis method of the present invention is shown in FIG. DETAILED DESCRIPTION

[0032] In order to make the contents of the present invention easier to understand, the technical solution of the present invention is further described below in conjunction with specific implementation methods, but the present invention is not limited to the scope of the embodiments.

[0033] Example 1

[0034] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), arylsulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12h. After the reaction was completed, the reaction mixture was filtered with diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 1 (isolation yield 83%) was obtained.

[0035]

[0036] 1 H NMR (400MHz, CDCl3) δ7.87-7.82 (m, 2H), 7.02-6.99 (m, 2H), 3.89 (s, 3H); 13 CNMR (151MHz, CDCl3) δ190.6 (t, J=26.5Hz), 164.6, 132.0, 129.9 (t, J=3.8Hz), 114.3, 55.5.

[0037] Example 2

[0038] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), arylsulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12h. After the reaction was completed, the reaction mixture was filtered with diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 2 (isolation yield 64%) was obtained.

[0039]

[0040] 1 H NMR (600MHz, CDCl3) δ7.85-7.82(m, 2H), 7.53-7.51(m, 2H); 13 C NMR (151MHz, CDCl3) δ190.6 (t, J=26.9Hz), 141.0, 134.6 (t, J=4.0Hz), 130.9, 129.5.

[0041] Example 3

[0042] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), arylsulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12h. After the reaction was completed, the reaction mixture was filtered with diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 3 (isolation yield 65%) was obtained.

[0043]

[0044] 1H NMR (400MHz, CDCl3) δ9.96 (s, 0.01H), 7.82-7.79 (m, 2H), 7.37-7.35 (m, 2H), 2.61-2.55(m, 1H), 1.91-1.74(m, 5H), 1.49-1.35(m, 4H), 1.30-1.24(m, 1H); 13 C NMR (101MHz, CDCl3) δ191.9 (t, J=26.6Hz), 155.4, 134.4 (t, J=3.5Hz), 129.9, 127.5, 44.9, 34.0, 26.7, 26.0.

[0045] Example 4

[0046] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), arylsulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12h. After the reaction was completed, the reaction mixture was filtered with diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 4 (isolation yield 72%) was obtained.

[0047]

[0048] 1 H NMR (400MHz, CDCl3) δ7.97-7.92(m, 2H), 7.39-7.36(m, 2H), 3.32(s, 3H), 1.97(s, 3H); 13 C NMR (151MHz, CDCl3) δ190.6 (t, J=27.1Hz), 170.0, 149.7, 134.9, 131.0, 127.4, 37.1, 22.6.

[0049] Example 5

[0050] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), arylsulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12h. After the reaction was completed, the reaction mixture was filtered with diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 5 (isolation yield 61%) was obtained.

[0051]

[0052] 1 H NMR (600MHz, CDCl3) δ7.67 (d, J=3.9Hz, 1H), 7.37-7.35 (m, 2H), 7.25 (d, J=3.9Hz, 1H), 7.09-7.07 (m, 1H); 13 C NMR (151MHz, CDCl3) δ182.4 (t, J=27.6Hz), 147.2, 141.7 (t, J=5.2Hz), 137.3, 136.0, 128.4, 127.1, 126.2, 124.3.

[0053] Example 6

[0054] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), arylsulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12h. After the reaction was completed, the reaction mixture was filtered with diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 6 (isolation yield 64%) was obtained.

[0055]

[0056] 1H NMR (600MHz, CDCl3) δ7.97-7.95 (m, 2H), 7.76 (d, J=8.1Hz, 2H), 7.66-7.63 (m, 2H), 7.49 (t, J=7.6Hz, 2H), 7.44-7.42 (m, 1H); 13 C NMR (151MHz, CDCl3) δ191.7 (t, J=26.6Hz), 147.2, 139.7, 135.1 (t, J=3.5Hz), 130.2, 129.0, 128.4, 127.7, 127.3.

[0057] Example 7

[0058] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), arylsulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12h. After the reaction was completed, the reaction mixture was filtered with diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 7 (isolation yield 52%) was obtained.

[0059]

[0060] 1 H NMR (600MHz, CDCl3) δ12.83 (s, 1H), 8.31 (d, J = 2.0Hz, 1H), 8.02-8.00 (m, 1H), 7.11 (d, J = 8.6Hz, 1H), 2.73 (s, 3H); 13 C NMR (151MHz, CDCl3) δ204.5, 189.3 (t, J=13.1Hz), 167.3, 137.0, 133.5, 128.2 (t, J=3.8Hz), 119.5, 110.8, 26.7.

[0061] Example 8

[0062] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), arylsulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12h. After the reaction was completed, the reaction mixture was filtered with diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 8 (isolation yield 63%) was obtained.

[0063]

[0064] 1 H NMR (600MHz, CDCl3) δ7.42 (dd, J=8.0, 1.6Hz, 1H), 7.34 (d, J=1.6Hz, 1H), 6.93 (d, J=8.0Hz, 1H), 6.08 (s, 2H); 13 C NMR (151MHz, CDCl3) δ190.1 (t, J=26.4Hz), 153.1, 148.7, 131.8 (t, J=3.5Hz), 128.6, 108.4, 106.9, 102.1.

[0065] Example 9

[0066] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), arylsulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12h. After the reaction was completed, the reaction mixture was filtered with diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 9 (isolation yield 46%) was obtained.

[0067]

[0068] 1H NMR (400MHz, CDCl3) δ8.17-8.14 (m, 1H), 7.83-7.80 (m, 2H), 7.59-7.55 (m, 1H), 7.03-6.96 (m, 6H), 6.88-6,85 (m, 1H), 6.76-6,73 (m, 1H), 5.64-5.56 (m, 1H), 4.23-4.08 (m, 2H), 1.49 (d, J=6.4Hz, 3H); 13 C NMR (101MHz, CDCl3) δ183.6 (t, J=14.3Hz), 164.1, 163.1, 156.2, 148.3, 146. 8, 138.7, 131.9, 130.8, 121.8, 116.8, 116.8, 116.0, 111.6, 71.0, 69.1, 17.0.

[0069] Example 10

[0070] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), arylsulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and stirred at 120°C for 12h. After the reaction was completed, the reaction mixture was filtered with diatomaceous earth, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography, using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 10 (isolation yield 73%) was obtained.

[0071]

[0072] 1 H NMR (600MHz, CDCl3) δ7.96-7.94 (m, 2H), 7.71-7.69 (m, 2H), 7.42 (t, J=8.0Hz, 1H ), 7.20-7.15 (m, 2H), 3.78 (q, J=7.2Hz, 1H), 3.70 (s, 3H), 1.54 (d, J=7.4Hz, 3H); 13C NMR (151MHz, CDCl3) δ191.5 (t, J=26.5Hz), 174.2, 159.7 (d, J=250.0Hz), 143.1 (t, J=7.8Hz), 141.6, 135.3, 130.7 (d, J=3 .4Hz), 129.8, 129.5 (d, J=3.3Hz), 126.5 (d, J=13.3Hz), 123.8 (d, J=3.9Hz), 115.5 (d, J=23.3Hz), 52.2, 44.9, 18.4, 18.3; 19 F NMR (377MHz, CDCl3) δ-116.8.

[0073] Example 11 Synthesis of target product with different ligands

[0074] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), ligand (0.04mmol, 20mol%), aryl sulfide compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv) were added in sequence, and the solvent was N,N-dimethylformamide solvent, and stirred at 120°C for 12h. The reaction results are shown in Table 1

[0075] Table 1 Synthesis results of different ligands

[0076]

[0077]

[0078] Example 12 Synthesis of target product from different palladium salts

[0079] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, a catalyst (0.02 mmol, 10 mol%), tri(1-naphthyl)phosphine as a ligand (0.04 mmol, 20 mol%), an aromatic sulfide compound (0.2 mmol, 1 equiv), sodium deuterated formate (0.6 mmol, 3 equiv), and triethylamine (0.4 mmol, 2 equiv) were added in sequence. The solvent was N,N-dimethylformamide solvent, and the mixture was stirred at 120°C for 12 hours.

[0080] Table 2 Synthesis results of different palladium salts

[0081] Palladium salts The NMR yield of the compound of formula 1 <![CDATA[PdCl2]]> 62％ <![CDATA[Pd(PPh3)2Cl2]]> 90％ <![CDATA[Pd(OAc)2]]> 52％

[0082] Example 13 Synthesis of target product using different alkaline reagents

[0083] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), aromatic sulfide salt compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), base (0.4mmol, 2equiv), and solvent N,N-dimethylformamide were added in sequence, and the mixture was stirred at 120°C for 12h.

[0084] Table 3 Synthesis results of different alkaline reagents

[0085]

[0086]

[0087] Example 14 Synthesis of target product using different organic solvents

[0088] In a reaction tube with a stirrer, under a carbon monoxide atmosphere, catalyst PdCl2(PPh3)2 (0.02mmol, 10mol%), tri(1-naphthyl)phosphine as a ligand (0.04mmol, 20mol%), aromatic sulfide salt compound (0.2mmol, 1equiv), sodium deuterated formate (0.6mmol, 3equiv), triethylamine (0.4mmol, 2equiv), and 1mL of solvent were added in sequence and stirred at 120°C for 12h.

[0089] Table 4 Synthesis results of different organic solvents

[0090] Organic solvents The NMR yield of the compound of formula 1 Toluene 30％ N,N-Dimethylformamide 90％ Acetonitrile 35％

[0091] Although the present invention has been described by the specific embodiments above, it should not be construed as being limited thereto; rather, the present invention encompasses the general aspects disclosed above. Various modifications and various embodiments are possible without departing from the spirit and scope of the present invention.

Claims

1. A method for synthesizing C-1 deuterated aromatic aldehydes using a palladium-catalyzed aryl sulfide compound, characterized in that: The method comprises the following steps: Dispersing an aryl sulfide salt, a deuterated salt, a palladium catalyst, a phosphine ligand, and a base in a solvent and reacting them in a carbon monoxide atmosphere, and obtaining a C-1 deuterated aromatic aldehyde after the reaction; The structural formula of the aryl sulfide salt compound is: The deuterated salt is sodium deuterated formate; the structural formula of the C-1 deuterated aromatic aldehyde is: Wherein R is a substituted or unsubstituted aromatic ring, a substituted or unsubstituted aromatic heterocycle; substitution includes mono- or di-substitution, and the substituent is selected from: C1-2 alkoxy, halogen, hydroxyl, acetyl, phenyl, C1-6 alkyl; The palladium catalyst is selected from any one or more of the following: PdCl2, PdCl2(PPh)2, and Pd(OAc)2; The phosphine ligand includes any one or more of the following structures: tri(1-naphthyl)phosphine, triphenylphosphine, tri(4-methoxyphenyl)phosphine; The base is selected from any one or more of the following: Na2CO3, iPr2NEt and Et3N; The solvent is selected from any one or more of the following: acetonitrile, N,N-dimethylformamide or toluene.

2. The method according to claim 1, characterized in that The synthetic route of the reaction is as follows:

3. The method according to claim 1, characterized in that The molar ratio of the aryl sulfide salt compound to sodium deuterated formate is 1:3, 1:2 or 1:1.

5.

4. The method according to claim 1, characterized in that: The amount of the phosphine ligand used is 20 mol % based on the arylsulfide salt compound.

5. The method according to claim 1, characterized in that The amount of the palladium catalyst used is 10 mol % relative to the arylsulfide salt compound.

6. The method according to claim 1, characterized in that The molar ratio of the base to the aryl sulfide salt compound is 2:1.

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