CN109574894B - Synthesis method of N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) - Google Patents
Synthesis method of N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) Download PDFInfo
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- CN109574894B CN109574894B CN201811512919.3A CN201811512919A CN109574894B CN 109574894 B CN109574894 B CN 109574894B CN 201811512919 A CN201811512919 A CN 201811512919A CN 109574894 B CN109574894 B CN 109574894B
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- -1 3- (dimethylamino) -3-propylsulfonyl Chemical group 0.000 title claims abstract description 32
- 150000003936 benzamides Chemical class 0.000 title claims abstract description 31
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 238000001308 synthesis method Methods 0.000 title description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 60
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 18
- 239000003054 catalyst Substances 0.000 claims abstract description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 15
- 239000011593 sulfur Substances 0.000 claims abstract description 15
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 10
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000005576 amination reaction Methods 0.000 claims abstract description 6
- 238000005987 sulfurization reaction Methods 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
- 125000004185 ester group Chemical group 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 238000003786 synthesis reaction Methods 0.000 claims description 9
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 239000000376 reactant Substances 0.000 claims description 5
- 150000001721 carbon Chemical group 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 claims description 3
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 3
- 150000008041 alkali metal carbonates Chemical group 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 3
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 229940054066 benzamide antipsychotics Drugs 0.000 claims 5
- 238000004440 column chromatography Methods 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 claims 1
- 238000005580 one pot reaction Methods 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 238000010189 synthetic method Methods 0.000 description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FEYGBGVBTKYFOF-UHFFFAOYSA-N 1-(sulfamoylamino)propane Chemical group CCCNS(N)(=O)=O FEYGBGVBTKYFOF-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- DECGHALMAREZMV-UHFFFAOYSA-N N'-propanethioylbenzohydrazide Chemical compound C(C1=CC=CC=C1)(=O)NNC(=S)CC DECGHALMAREZMV-UHFFFAOYSA-N 0.000 description 1
- QIOZLISABUUKJY-UHFFFAOYSA-N Thiobenzamide Chemical compound NC(=S)C1=CC=CC=C1 QIOZLISABUUKJY-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- UEXCJVNBTNXOEH-UHFFFAOYSA-N phenyl acethylene Natural products C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical group CCCS(N)(=O)=O DROIHSMGGKKIJT-UHFFFAOYSA-N 0.000 description 1
- WPZSAUFQHYFIPG-UHFFFAOYSA-N propanethioamide Chemical group CCC(N)=S WPZSAUFQHYFIPG-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/38—Amides of thiocarboxylic acids
- C07C327/40—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C327/42—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a method for synthesizing N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I), which is prepared from substituted benzoylAllylamine (II), sulfur and N, N-Dimethylformamide (DMF) are directly prepared by sulfuration and amination of olefinic bond terminal carbon connected with saturated carbon atoms in the presence of a catalyst or without the catalyst, and the reaction formula is as follows:
(ii) a Substituted benzoylallylamines (II) wherein R1~R5The same or different hydrogen, alkyl, halogenated alkyl, aryl, halogen, nitro, sulfocarboxyl, carboxyl, ester group and cyano. The invention uses substituted benzoylallylamine (II) which is easily obtained in the market as an initial raw material, and quickly and conveniently obtains the N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) through one-step reaction. The invention has the advantages of novel and convenient reaction process, mild and easily-controlled reaction conditions, simple reaction solvent system and easy post-treatment.
Description
Technical Field
The invention relates to a method for synthesizing intermediates of chemical industry, medicine and pesticide, in particular to a novel method for synthesizing N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I).
Background
The N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) is an important chemical, medicine and pesticide intermediate, but the traditional synthetic method has the problems of multiple steps, difficult raw material acquisition, harsh reaction conditions and the like, and limits the effective acquisition of the N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide.
The documents Organic Letters, 2014, 16 (1), 310-; organic & Biomolecular Chemistry, 12(4), 700-707 reported the synthesis of thiophenylacetamides using phenylacetylene halides; organic Letters, 2014, 16(14), 3624-; chemistry select, 2017, 2(20), 5532-; advanced Synthesis & Catalysis, 2017, 359(24), 4300-;
the synthetic methods referred to above have obvious drawbacks: 1) the acetylene bonds and olefinic bonds involved in the reaction are both conjugated with aromatic rings and there is no information or suggestion that there is no conjugated acetylene bond and olefinic bond; 2) the reaction involving the acetylene bond and the olefinic bond produces only thioacetamide and thiobenzamide, but not thioaropionamide. 3) The method for synthesizing the thioacetamide by utilizing the acetophenone and the derivative thereof cannot be directly used for synthesizing the benzamido thiopropionamide (I).
Therefore, it is necessary to provide a synthesis method with mild and easily controlled reaction conditions, simple reaction system, few reaction steps and easily available raw materials.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a synthesis method for synthesizing the N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I), which is convenient, mild and easily controlled in reaction conditions, simple in reaction system, few in reaction steps and easy in raw material acquisition.
The purpose of the invention is realized as follows:
a synthetic method of N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) is directly prepared by substituted benzoylallylamine (II), sulfur (S) and N, N-Dimethylformamide (DMF) in the presence of a catalyst or no catalyst through a one-step reaction process, and the reaction formula is as follows:
the synthesis method of the N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) comprises the steps of carrying out sulfuration and amination on the carbon at the end position of an olefinic bond connected with a saturated carbon atom to obtain substituted propylsulfonyl amide functional groups in a position-selective manner, and further conveniently synthesizing the N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I);
the substituted benzoylallylamine (II) wherein R1~R5The same or different hydrogen, alkyl, halogenated alkyl, aryl, halogen, nitro, sulfocarboxyl, carboxyl, ester group and cyano;
n, N-Dimethylformamide (DMF) used in the reaction is a reaction solvent and a reactant.
The catalyst is alkali metal carbonate, including potassium carbonate, sodium carbonate, cesium carbonate and lithium carbonate; alkali metal hydroxides include sodium hydroxide, potassium hydroxide, lithium hydroxide, and cesium hydroxide; the organic base includes triethylamine, triethylenediamine and pyridine.
The feeding molar ratio of the substituted benzoylallylamine (II) to sulfur is 1: 1-10;
the feeding molar ratio of the substituted benzoylallylamine (II) to the catalyst is 1: 0-5;
the feeding molar ratio of the substituted benzoylallyl amine (II) to the reaction solvent is 1: 20-50;
the feeding mode is that the substituted benzoylallylamine (II) and sulfur are put into N, N-Dimethylformamide (DMF);
the reaction time is 1-20 hours, and the reaction temperature is 60-150 DEG CoC。
The post-treatment method of the reaction process for preparing the N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) comprises the following steps: and after the reaction is finished, cooling the reaction system to room temperature, filtering, removing excessive sulfur and catalyst, evaporating excessive N, N-Dimethylformamide (DMF) from the filtrate under negative pressure, washing the residue, extracting, concentrating, recrystallizing or carrying out silica gel column chromatography to obtain pure N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I).
Has the positive and beneficial effects that: the invention discloses a new synthesis method of a chemical intermediate N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I), which takes substituted benzoylallylamine (II) which is easily obtained in the market as a starting material and obtains a target product conveniently and quickly through one-step reaction. The method selectively obtains the substituted propanethioamide functional group in position through sulfuration and amination of the end site carbon of the olefinic bond connected with the saturated carbon atom, and provides a convenient synthetic approach for synthesizing and obtaining the N- (3- (dimethylamino) -3-propanethioacyl) -substituted benzamide (I). The synthesis method has the advantages of novel and convenient reaction process, mild and easily-controlled reaction conditions, simple reaction solvent system and easy post-treatment.
Detailed Description
The invention will be further described with reference to specific examples:
a synthetic method of N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) is directly prepared by substituted benzoylallylamine (II), sulfur (S) and N, N-Dimethylformamide (DMF) in the presence of a catalyst or no catalyst through a one-step reaction process, and the reaction formula is as follows:
the synthesis method completely and newly obtains the substituted propyl sulfamide functional group through sulfuration and amination of the end position carbon of the olefinic bond connected with the saturated carbon atom, and then conveniently synthesizes the N- (3- (dimethylamino) -3-propyl sulfenyl) -substituted benzamide (I).
The substituted benzoylallylamines (II), R thereof1~R5The same or different hydrogen, alkyl, halogenated alkyl, aryl, halogen, nitro, sulfocarboxyl, carboxyl, ester group and cyano.
N, N-Dimethylformamide (DMF) used in the reaction is a reaction solvent and a reactant.
The catalyst is alkali metal carbonate, including potassium carbonate, sodium carbonate, cesium carbonate and lithium carbonate; alkali metal hydroxides include sodium hydroxide, potassium hydroxide, lithium hydroxide, and cesium hydroxide; the organic base includes triethylamine, triethylenediamine and pyridine.
The feeding molar ratio of the substituted benzoylallylamine (II) to sulfur is 1: 1-10;
the feeding molar ratio of the substituted benzoylallylamine (II) to the catalyst is 1: 0-5;
the feeding molar ratio of the substituted benzoylallylamine (II) to the reaction solvent is 1: 20-50 parts of;
the feeding mode is that the substituted benzoylallylamine (II) and calculated amount of sulfur are put into N, N-Dimethylformamide (DMF) with proper amount;
the reaction process for preparing the N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) has the reaction time of 1-20 hours and the reaction temperature of 60-150 DEG CoC。
The post-treatment method of the reaction process for preparing the N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) comprises the following steps: and after the reaction is finished, cooling the reaction system to room temperature, filtering, evaporating excessive N, N-Dimethylformamide (DMF) under negative pressure, washing residues, extracting, concentrating, recrystallizing or carrying out silica gel column chromatography to obtain pure N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I).
Example 1
Synthesis of N- (3- (dimethylamino) -3-propylsulfonyl) -benzamide
Benzoylallylamine (1.61 g, 10 mmol) was added to a three-necked flask containing N, N-Dimethylformamide (DMF) (16 g, 0.22 mol) with sulfur (1.6 g, 50 mmol), and the temperature was gradually increased to 120 deg.C under normal pressureoC, reacting for 12 hours, and analyzing a thin layer to completely convert reactants. The reaction was then cooled to room temperature and filtered to remove excess sulfur. The filtrate is freed of the solvent in vacuo, the residue is washed with water and extracted with dichloromethane. Drying the dichloromethane extractThe mixture was dried and concentrated, and the residue was separated by silica gel column chromatography to give 1.44g of N- (3- (dimethylamino) -3-propylsulfonyl) -benzamide in 61% yield.
1H NMR (400MHz, CDCl3) : 7.873-7.78(m, 2H)；7.56 (br s, 1H)；7.49-7.27(m, 3H)；3.95-3.91 (q,J= 6, 5.6 Hz, 2H)；3.51 (s, 3H)；3.33(s, 3H)；2.97-2.94( t,J= 5.6 Hz, 2H)。13C NMR (100MHz, CDCl3) : 201.0, 167.2, 134.4, 131.5,128.5, 127.0, 44.6, 41.6, 41.3, 38.0。HPLC-MSm/z: 259.0872 [M+Na]＋。
Example 2
Synthesis of 2-chloro-N- (3- (dimethylamino) -3-propylthioacyl) -6- (1H-1, 2, 4-triazol-1-yl) benzamide
N-allyl-2-chloro-6- (1H-1, 2, 4-triazol-1-yl) benzamide (2.6 g, 10 mmol) was added to a three-necked reaction flask containing N, N-Dimethylformamide (DMF) (26 g, 0.35 mol), while adding sulfur (2.6 g, 80 mmol), K2CO3(2.8 g, 20 mmol) and the temperature was gradually raised to 110 ℃ under normal pressureoC, reacting for 15 hours, and analyzing a thin layer to completely convert reactants. The reaction was then cooled to room temperature and filtered to remove excess sulfur and potassium carbonate. The filtrate is freed of the solvent in vacuo, the residue is washed with water and extracted with dichloromethane. The dichloromethane extract was dried and concentrated, and the residue was separated by silica gel column chromatography to give 2.2 g of 2-chloro-N- (3- (dimethylamino) -3-propylsulfonyl) -6- (1-hydro-1, 2, 4-triazol-1-yl) benzamide, yield 65%.
1H NMR (400MHz, CDCl3) : 8.48 (s, 1H)；8.00 (s, 1H)；7.51-7.46 (m, 3H)；7.08-7.06 (t,J=5.6Hz, 1H)；3.84-3.80 (q,J= 6, 5.6 Hz, 2H)；3.47 (s, 3H)；3.31(s, 3H)；2.72-2.69 ( t,J= 5.6 Hz, 2H)。13C NMR (100MHz, CDCl3) : 199.9,164.0, 152.3, 144.0, 135.2, 132.3, 132.0, 130.8, 130.3, 123.8, 44.6, 41.5,40.2, 38.1。 HPLC-MSm/z: 360.0664 [M+Na]＋。
The invention takes substituted benzoylallylamine (II) which is easily obtained in the market as an initial raw material, and obtains an N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide product (I) through one-step reaction in the presence of sulfur, DMF and a catalyst. The method directly converts the allyl olefinic bond terminal carbon into thioamide tubular energy group through sulfuration and amination, thereby providing a convenient synthetic approach for obtaining the N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) product. The synthesis method has the advantages of novel, simple and convenient reaction process, mild and easily-controlled reaction conditions, simple reaction solvent system, convenient post-treatment and the like.
The above embodiments are only for illustrating the preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention within the knowledge of those skilled in the art should be considered as the protection scope of the present application.
Claims (7)
1. A method for synthesizing N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) is characterized in that: substituted benzoylallylamine (II), sulfur and N, N-dimethylformamide are subjected to sulfuration and amination of carbon at the end of an olefinic bond connected with a saturated carbon atom in the presence of a catalyst or without the catalyst to obtain substituted prothiocyanide functional group in a position-selective manner, and then N- (3- (dimethylamino) -3-propylthioacyl) -substituted benzamide (I) is synthesized, wherein the reaction formula is as follows:
the substituted benzoylallylamine (II) wherein R1~R5The same or different hydrogen, alkyl, halogenated alkyl, aryl, halogen, nitro, sulfocarboxyl, carboxyl, ester group and cyano.
2. The process according to claim 1 for the synthesis of N- (3- (dimethylamino) -3-propanethioacyl) -substituted benzamides (I) characterized by: the feeding molar ratio of the substituted benzoylallylamine (II) to sulfur is 1: 1-10.
3. The method for synthesizing N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) according to claim 1, wherein: the N, N-Dimethylformamide (DMF) is a reactant and a reaction solvent, and the feeding molar ratio of the substituted benzoylallylamine (II) to the N, N-Dimethylformamide (DMF) is 1: 20-50.
4. The process according to claim 1 for the synthesis of N- (3- (dimethylamino) -3-propanethioacyl) -substituted benzamides (I) characterized by: the catalyst is alkali metal carbonate selected from potassium carbonate, sodium carbonate, cesium carbonate and lithium carbonate; the alkali metal hydroxide is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide and cesium hydroxide; or an organic base selected from triethylamine, triethylenediamine and pyridine.
5. The process according to claim 1 or 4 for the synthesis of N- (3- (dimethylamino) -3-propanethioacyl) -substituted benzamides (I) characterized by the following steps: the molar ratio of the substituted benzoylallylamine (II) to the catalyst is 1: 0-5.
6. The process according to claim 1 for the synthesis of N- (3- (dimethylamino) -3-propanethioacyl) -substituted benzamides (I) characterized by: the reaction process has the reaction time of 1-20 hours and the reaction temperature of 60-150 DEG CoC。
7. The process according to claim 1 for the synthesis of N- (3- (dimethylamino) -3-propanethioacyl) -substituted benzamides (I) characterized by: the post-treatment method of the reaction process comprises the following steps: and after the reaction is finished, cooling the reaction system to room temperature, filtering, evaporating excessive N, N-Dimethylformamide (DMF) under negative pressure, washing residues, extracting, concentrating, recrystallizing or carrying out column chromatography to obtain the N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I).
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| CN201811512919.3A Expired - Fee Related CN109574894B (en) | 2018-12-11 | 2018-12-11 | Synthesis method of N- (3- (dimethylamino) -3-propylsulfonyl) -substituted benzamide (I) |
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