CN116874418A - Process for preparing 2- (methylsulfonyl) nicotinaldehyde - Google Patents

Process for preparing 2- (methylsulfonyl) nicotinaldehyde Download PDF

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CN116874418A
CN116874418A CN202310790615.8A CN202310790615A CN116874418A CN 116874418 A CN116874418 A CN 116874418A CN 202310790615 A CN202310790615 A CN 202310790615A CN 116874418 A CN116874418 A CN 116874418A
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methylsulfonyl
methyl
nicotinaldehyde
reaction
manufacturing according
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方慧康
苏强
林进
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Suzhou Yuanqi Material Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • C07D213/71—Sulfur atoms to which a second hetero atom is attached
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/803—Processes of preparation

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

The invention relates to a preparation method of 2- (methylsulfonyl) nicotinaldehyde, belonging to the technical field of organic synthesis. The invention comprises the following steps: under the protective atmosphere, 2-mercaptonicotinic acid and potassium carbonate are dissolved in an organic solvent, methyl iodide is added for reaction, and white solid 2-methylthio nicotinic acid methyl ester is obtained; dissolving the obtained 2-methylthio methyl nicotinate and sodium tungstate hydrate in acetic acid, adding an oxidant at the temperature of-5 ℃ to react at room temperature, and collecting a product to obtain white solid 2- (methylsulfonyl) methyl nicotinate; under the protective atmosphere, the obtained methyl 2- (methylsulfonyl) nicotinate is dissolved in tetrahydrofuran, a reducing agent is added at the temperature of-83 ℃ to-73 ℃ for stirring reaction, and after the reaction is finished, the product is collected to obtain the 2- (methylsulfonyl) nicotinaldehyde. The purity of the product 2- (methylsulfonyl) nicotinaldehyde obtained by the invention is 97% -99%, and the total yield is more than 70%.

Description

Process for preparing 2- (methylsulfonyl) nicotinaldehyde
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of 2- (methylsulfonyl) nicotinaldehyde.
Background
2- (methylsulfonyl) nicotinaldehyde is an important chemical raw material and an organic building block, is an important intermediate for synthesizing nicotinamide and nicotinic acid ester compounds, and researches show that the nicotinamide compounds play an important role in resisting skin aging and are used as additives of skin care products, and in addition, 2- (methylsulfonyl) nicotinaldehyde is also an essential structural unit for synthesizing a plurality of novel antihypertensive drugs, so that the research on how to prepare 2- (methylsulfonyl) nicotinaldehyde with high efficiency, high yield and low cost is a subject with important application value.
In the prior art, most of raw materials for preparing the methyl 2- (methylsulfonyl) nicotinate are 2-methylthio nicotinic acid, and the method has the problems of higher cost of starting materials, complex post-reaction treatment and the like. Although literature (Heteromyces 2010,81,413;Journal ofthe Korean Chemical Society 2021,65,166) uses 2-mercaptonicotinic acid as a starting material and uses sulfuric acid as a catalyst to carry out reflux reaction in methanol to obtain the methyl 2-methylthionicotinate, the method has the problems of low yield, long reaction time and the like, and relates to the use and post-treatment of the sulfuric acid, thereby having higher requirements on the production environment. The reaction route is as follows:
from this, the prior art has the disadvantages of high cost of starting materials, lower reaction conversion rate, long reaction time and the like in the process of preparing the 2- (methylsulfonyl) methylnicotinate, and no report of synthesizing 2- (methylsulfonyl) nicotinaldehyde by using the 2- (methylsulfonyl) methylnicotinate is available in the prior art. Accordingly, there is a need to provide a process for preparing 2- (methylsulfonyl) nicotinaldehyde in high yield and at low cost.
Disclosure of Invention
In order to solve the technical problems, the invention provides a preparation method of 2- (methylsulfonyl) nicotinaldehyde. The 2- (methylsulfonyl) nicotinaldehyde has more active aldehyde groups, can be conveniently applied to various chemical reactions and is derived into various structural units, and based on the reasons, the invention provides a method for preparing the 2- (methylsulfonyl) nicotinaldehyde with high yield and low cost.
The invention is realized by the following steps:
the invention aims to provide a preparation method of 2- (methylsulfonyl) nicotinaldehyde, which comprises the following steps:
(1) Under the protective atmosphere, 2-mercaptonicotinic acid and an alkaline agent are dissolved in an organic solvent, methyl iodide is added for reaction, and 2-methylthio nicotinic acid methyl ester is obtained;
(2) Reacting the methyl 2-methylthionicotinate obtained in the step (1) with a catalytic system in an organic solvent to obtain methyl 2- (methylsulfonyl) nicotinate;
(3) And (3) under the protective atmosphere, dissolving the methyl 2- (methylsulfonyl) nicotinate obtained in the step (2) in an organic solvent, adding a reducing agent, and stirring for reaction to obtain the 2- (methylsulfonyl) nicotinaldehyde.
In one embodiment of the present invention, the organic solvent is selected from one or more of acetonitrile, tetrahydrofuran, acetic acid, N-dimethylformamide and N, N-dimethylacetamide.
In one embodiment of the present invention, in the step (1), the molar ratio of the 2-mercaptonicotinic acid, methyl iodide and the alkaline agent is 1:2:2.5 to 1:4:5.
In one embodiment of the invention, in step (1), the reaction time is 4 to 8 hours.
In one embodiment of the invention, the alkaline agent is selected from one or more of potassium carbonate, potassium bicarbonate, dipotassium hydrogen phosphate, triethylamine and N, N-diisopropylethylamine.
In one embodiment of the present invention, in the step (2), the catalytic system is sodium tungstate/hydrogen peroxide, sodium periodate/rhodium chloride, cyanuric acid/sodium hypochlorite or mCPBA.
In one embodiment of the invention, the molar ratio of the methyl 2-methylthionicotinate to the hydrogen peroxide and the sodium tungstate in the catalytic system is 1:2:0.05-1:2.5:0.1.
In one embodiment of the invention, in step (2), the reaction time is 8 to 12 hours.
In one embodiment of the present invention, in the step (3), the molar ratio of the methyl 2- (methylsulfonyl) nicotinate to the reducing agent is 1:1 to 1:1.2.
In one embodiment of the present invention, in step (3), the reducing agent is diisobutylaluminum hydride and/or red aluminum.
In one embodiment of the present invention, in step (3), the reaction conditions are: reacting for 3-6 h at-83-73 ℃.
In one embodiment of the invention, in step (3), the method further comprises subjecting the 2- (methylsulfonyl) nicotinaldehyde to a recrystallization treatment.
In one embodiment of the present invention, the recrystallization treatment method comprises: adding ethyl acetate into the 2- (methylsulfonyl) nicotinaldehyde crude product, stirring and heating, controlling the temperature at 45-50 ℃, filtering to remove insoluble substances, adding n-hexane into the filtrate, controlling the temperature at about 45 ℃, stirring for a period of time, removing the heating, cooling until solid is separated out, and filtering to obtain the product.
In one embodiment of the invention, the synthetic route for the 2- (methylsulfonyl) nicotinaldehyde of the invention is as follows:
compared with the prior art, the technical scheme of the invention has the following advantages:
(1) The invention synthesizes the target product 2- (methylsulfonyl) nicotinaldehyde with high yield and high purity by taking 2-mercaptonicotinic acid as the initial raw material through three steps of methylation, oxidation and reduction, the raw material is cheap and easy to obtain, the reaction is easy to operate, the post-treatment is simpler, the synthesis cost is effectively reduced, and simultaneously, the higher purity can be stably obtained, thereby having good prospect of industrial production.
(2) The nuclear magnetic resonance hydrogen spectrum of the synthesized product shows that the final product synthesized by the invention is 2- (methylsulfonyl) nicotinaldehyde, the purity is 97% -99%, and the total yield is more than 70%.
Drawings
In order that the invention may be more readily understood, a more particular description of the invention will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings, in which,
FIG. 1 is a nuclear magnetic resonance spectrum of 2- (methylsulfonyl) nicotinaldehyde in the present invention.
Detailed Description
The present invention will be further described with reference to the accompanying drawings and specific examples, which are not intended to be limiting, so that those skilled in the art will better understand the invention and practice it.
Example 1
(1) Synthesis of methyl 2-methylthionicotinate
To a 500mL three-necked flask, 2-mercaptonicotinic acid (15.5 g,0.1 mol), potassium carbonate (34.6 g,0.25 mol) and DMF (75 mL) were added under nitrogen atmosphere, and the temperature was slowly lowered to 0.+ -. 5 ℃. Methyl iodide (28.4 g,0.2 mol) was slowly added dropwise (note that the temperature was not higher than 5 ℃ C.), and the reaction was resumed at room temperature for 4 hours after the completion of the dropwise addition. Then, 1M diluted hydrochloric acid was added to adjust the pH to about 2 to 3, at this time, solids were precipitated, about 300mL of water was slowly added, and the mixture was stirred at 0℃for 0.5 hours, filtered, and the solids were washed with cold water to give 16.7g of methyl 2-methylthionicotinate as a white solid, with a yield of 91.2%.
(2) Synthesis of methyl 2- (methylsulfonyl) nicotinate
In a 250mL three-necked flask, methyl 2-methylthionicotinate (9.15 g,50 mmol), sodium tungstate hydrate (0.82 g,2.5 mmol) and acetic acid (50 mL) were added to a 500mL three-necked flask, the temperature was lowered to 0.+ -. 5 ℃, 30wt% hydrogen peroxide (11.3 g,100 mmol) was slowly added, and the reaction was resumed at room temperature for 8 hours after the completion of the dropwise addition. After the reaction was completed, 200mL of water was added to the reaction mixture, and extracted with ethyl acetate (100 ml×3), the organic phase was washed successively with water, brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give 10.0g of methyl 2- (methylsulfonyl) nicotinate as a white solid in 93.6% yield.
(3) Synthesis of 2- (methylsulfonyl) nicotinaldehyde
To a 500mL three-necked flask, methyl 2- (methylsulfonyl) nicotinate (8.6 g,40 mmol) and tetrahydrofuran (100 mL) were added under nitrogen atmosphere and slowly cooled to-78.+ -. 5 ℃. DIBAL (40mL,40mmol,1M in n-hexane) was slowly added dropwise. The temperature is controlled to be minus 78 plus or minus 5 ℃ and the reaction is stirred for 3 hours. After the system is reacted completely, adding 1.6mL of water, 1.6mL of 15% NaOH solution and 4mL of water for quenching, adding anhydrous sodium sulfate, stirring for 0.5h, filtering, concentrating an organic phase to dryness to obtain a crude product, adding ethyl acetate into a 2- (methylsulfonyl) nicotinaldehyde crude product, stirring and heating, controlling the temperature to be 45-50 ℃, filtering to remove insoluble matters, adding n-hexane into the filtrate, controlling the temperature to be about 45 ℃, after stirring for a period of time, removing heating, cooling until solid is separated out, filtering to obtain 6.1g of white solid 2- (methylsulfonyl) nicotinaldehyde, and obtaining the yield of 82.7%. The overall yield of the final product was 70.6%.
The product was characterized by nuclear magnetism as shown in figure 1.
Example 2
(1) Synthesis of methyl 2-methylthionicotinate
To a 500mL three-necked flask, 2-mercaptonicotinic acid (15.5 g,0.1 mol), potassium carbonate (34.6 g,0.25 mol) and acetonitrile (100 mL) were added under nitrogen atmosphere, and the temperature was slowly lowered to 0.+ -. 5 ℃. Methyl iodide (28.4 g,0.2 mol) was slowly added dropwise (note that the temperature was not higher than 5 ℃ C.), and the reaction was resumed at room temperature for 4 hours after the completion of the dropwise addition. Then, 1M diluted hydrochloric acid was added to adjust the pH to about 2 to 3, at this time, solids were precipitated, about 300mL of water was slowly added, and the mixture was stirred at 0℃for 0.5 hours, filtered, and the solids were washed with cold water to give 15.3g of methyl 2-methylthionicotinate as a white solid in a yield of 83.6%.
(2) Synthesis of methyl 2- (methylsulfonyl) nicotinate
In a 250mL three-necked flask, methyl 2-methylthionicotinate (9.15 g,50 mmol), sodium tungstate hydrate (0.82 g,2.5 mmol) and acetic acid (50 mL) were added to a 500mL three-necked flask, the temperature was lowered to 0.+ -. 5 ℃, 30wt% hydrogen peroxide (11.3 g,100 mmol) was slowly added, and the reaction was resumed at room temperature for 12 hours after the dropwise addition. After the reaction was completed, 200mL of water was added to the reaction mixture, and extracted with ethyl acetate (100 ml×3), the organic phase was washed successively with water, brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give 9.6g of methyl 2- (methylsulfonyl) nicotinate as a white solid in 89.8% yield.
(3) Synthesis of 2- (methylsulfonyl) nicotinaldehyde
To a 500mL three-necked flask, methyl 2- (methylsulfonyl) nicotinate (8.6 g,40 mmol) and tetrahydrofuran (100 mL) were added under nitrogen atmosphere and slowly cooled to-78.+ -. 5 ℃. DIBAL (40mL,40mmol,1M DIBAL in n-hexane) was slowly added dropwise. The temperature is controlled to be minus 78 plus or minus 5 ℃ and the reaction is stirred for 6 hours. After the system is reacted completely, adding 1.6mL of water, 1.6mL of 15% NaOH solution and 4mL of water for quenching, adding anhydrous sodium sulfate, stirring for 0.5h, filtering, concentrating an organic phase to dryness to obtain a crude product, adding ethyl acetate into a 2- (methylsulfonyl) nicotinaldehyde crude product, stirring and heating, controlling the temperature to be 45-50 ℃, filtering to remove insoluble matters, adding n-hexane into the filtrate, controlling the temperature to be about 45 ℃, after stirring for a period of time, removing heating, cooling until solid is separated out, filtering to obtain 6.3g of white solid 2- (methylsulfonyl) nicotinaldehyde, and obtaining the yield of 85.4%. The final product yield was 64.1%.
Example 3
(1) Synthesis of methyl 2-methylthionicotinate
2-mercaptonicotinic acid (62.1 g,0.4 mol), potassium carbonate (276 g,2 mol) and DMF (300 mL) were added to a 2L three-necked flask under nitrogen atmosphere, and the temperature was lowered to 0.+ -. 5 ℃. Methyl iodide (125.2 g,1.6 mol) was slowly added dropwise (note that the temperature was not higher than 5 ℃ C.), and the reaction was resumed at room temperature for 8 hours after the completion of the dropwise addition. Then 1M dilute hydrochloric acid is added to adjust the pH value to about 2-3, at this time, solid is separated out, about 1.2L of water is slowly added, and the mixture is stirred for 0.5h at 0 ℃, filtered, and the solid is washed with cold water to obtain 67.8g of white solid methyl 2-methylthionicotinate, and the yield is 92.6%.
(2) Synthesis of methyl 2- (methylsulfonyl) nicotinate
In a 250mL three-necked flask, methyl 2-methylthionicotinate (45.8 g,0.25 mol), sodium tungstate hydrate (6 g,0.02 mol) and acetic acid (200 mL) were added to a 2L three-necked flask, the temperature was lowered to 0.+ -. 5 ℃, 30wt% hydrogen peroxide (56.5 g,0.55 mol) was slowly added, and the reaction was resumed at room temperature for 8 hours after the dropwise addition. After completion of the reaction, 800mL of water was added to the reaction mixture and extracted with ethyl acetate (250 mL x 3), the organic phase was washed successively with water, brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give 9.9g of methyl 2- (methylsulfonyl) nicotinate as a white solid in 92.9% yield.
(3) Synthesis of 2- (methylsulfonyl) nicotinaldehyde
To a 2L three-necked flask, methyl 2- (methylsulfonyl) nicotinate (43 g,0.2 mmol) and tetrahydrofuran (500 mL) were added under nitrogen atmosphere and slowly cooled to-78.+ -. 5 ℃. DIBAL (240mL,0.24mol,1M DIBAL in n-hexane) was slowly added dropwise. The temperature is controlled to be minus 78 plus or minus 5 ℃ and the reaction is stirred for 3 hours. After the system is completely reacted, 9.6mL of water, 9.6mL of 15% NaOH solution and 24mL of water are sequentially added for quenching, anhydrous sodium sulfate is added, stirring is carried out for 0.5h, filtering is carried out, the organic phase is concentrated to dryness, the crude product is obtained, and ethyl acetate/n-hexane is used for recrystallization to obtain 32.7g of white solid 2- (methylsulfonyl) nicotinaldehyde, and the yield is 88.6%. The overall yield of the final product was 76.2%.
Comparative example 1
The comparative example provides a synthesis method of methyl 2-methylthionicotinate, which comprises the following specific steps:
2-mercaptonicotinic acid (62.1 g,0.4 mol), concentrated sulfuric acid (98%, 10 mL) and methanol (1L) were added to a 2L three-necked flask under nitrogen atmosphere, and the mixture was refluxed for 24 hours after the completion of the dropwise addition. Then adding sodium carbonate solution for quenching, extracting ethyl acetate (200 mL of 3) and drying anhydrous sodium sulfate, separating by flash column chromatography (silica gel), wherein the eluent is n-hexane/ethyl acetate (20:1, v/v), and obtaining 32.4g of white solid methyl 2-methylthio nicotinate, and the yield is 44.3%.
Comparative example 2
The preparation of 2- (methylsulfonyl) nicotinaldehyde in this comparative example was similar to that of example 1, except that:
the reducing agent used in the step (3) is LiAlH 4 The method comprises the steps of carrying out a first treatment on the surface of the The yield of the finally obtained white solid was 32.4%.
It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations and modifications of the present invention will be apparent to those of ordinary skill in the art in light of the foregoing description. It is not necessary here nor is it exhaustive of all embodiments. And obvious variations or modifications thereof are contemplated as falling within the scope of the present invention.

Claims (10)

1. A method for preparing 2- (methylsulfonyl) nicotinaldehyde, comprising the steps of:
(1) Under the protective atmosphere, 2-mercaptonicotinic acid and an alkaline agent are dissolved in an organic solvent, methyl iodide is added for reaction, and 2-methylthio nicotinic acid methyl ester is obtained;
(2) Reacting the methyl 2-methylthionicotinate obtained in the step (1) with a catalytic system in an organic solvent to obtain methyl 2- (methylsulfonyl) nicotinate;
(3) And (3) under the protective atmosphere, dissolving the methyl 2- (methylsulfonyl) nicotinate obtained in the step (2) in an organic solvent, adding a reducing agent, and stirring for reaction to obtain the 2- (methylsulfonyl) nicotinaldehyde.
2. The method of manufacturing according to claim 1, characterized in that: the organic solvent is selected from one or more of acetonitrile, tetrahydrofuran, acetic acid, N-dimethylformamide and N, N-dimethylacetamide.
3. The method of manufacturing according to claim 1, characterized in that: in the step (1), the molar ratio of the 2-mercaptonicotinic acid to the methyl iodide to the alkaline agent is 1:2:2.5-1:4:5.
4. The method of manufacturing according to claim 1, characterized in that: in the step (1), the alkaline agent is selected from one or more of potassium carbonate, potassium bicarbonate, dipotassium hydrogen phosphate, triethylamine and N, N-diisopropylethylamine.
5. The method of claim 1, wherein: in the step (2), the catalytic system is sodium tungstate/hydrogen peroxide, sodium periodate/rhodium chloride, cyanuric acid/sodium hypochlorite or mCPBA.
6. The method of manufacturing according to claim 1, characterized in that: in the step (2), the reaction time is 8-12 h.
7. The method of manufacturing according to claim 1, characterized in that: in the step (3), the molar ratio of the 2- (methylsulfonyl) methyl nicotinate to the reducing agent is 1:1-1:1.2.
8. The method of manufacturing according to claim 1, characterized in that: in the step (3), the reducing agent is diisobutylaluminum hydride and/or red aluminum.
9. The method of manufacturing according to claim 1, characterized in that: in the step (3), the reaction conditions are as follows: reacting for 3-6 h at-83-73 ℃.
10. The method of manufacturing according to claim 1, characterized in that: in the step (3), the method also comprises the step of recrystallizing the 2- (methylsulfonyl) nicotinaldehyde.
CN202310790615.8A 2023-06-30 2023-06-30 Process for preparing 2- (methylsulfonyl) nicotinaldehyde Pending CN116874418A (en)

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