CN109574894A - A kind of (I) synthetic method for the benzamide that N- (3- (dimethyl amido) -3- rosickyite acyl group)-replaces - Google Patents
A kind of (I) synthetic method for the benzamide that N- (3- (dimethyl amido) -3- rosickyite acyl group)-replaces Download PDFInfo
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- CN109574894A CN109574894A CN201811512919.3A CN201811512919A CN109574894A CN 109574894 A CN109574894 A CN 109574894A CN 201811512919 A CN201811512919 A CN 201811512919A CN 109574894 A CN109574894 A CN 109574894A
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- Prior art keywords
- rosickyite
- acyl group
- benzamide
- reaction
- dimethyl amido
- Prior art date
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- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 125000002252 acyl group Chemical group 0.000 title claims abstract description 34
- 238000010189 synthetic method Methods 0.000 title claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 51
- -1 benzoyl allylamine Chemical compound 0.000 claims abstract description 25
- VVJKKWFAADXIJK-UHFFFAOYSA-N allylamine Natural products NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 claims abstract description 23
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000005864 Sulphur Substances 0.000 claims abstract description 17
- 239000003054 catalyst Substances 0.000 claims abstract description 16
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 12
- 238000006467 substitution reaction Methods 0.000 claims abstract description 10
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000005977 Ethylene Substances 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 238000005576 amination reaction Methods 0.000 claims abstract description 6
- 238000012805 post-processing Methods 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 150000001721 carbon Chemical group 0.000 claims abstract description 5
- 238000004073 vulcanization Methods 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
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 42
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- 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 compound [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
- 150000001408 amides Chemical class 0.000 claims description 7
- 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 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
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- 239000003513 alkali Substances 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
- 238000001914 filtration Methods 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims 1
- 229910052744 lithium Inorganic materials 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 239000007858 starting material Substances 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 13
- 238000000034 method Methods 0.000 description 11
- LSBDFXRDZJMBSC-UHFFFAOYSA-N Amide-Phenylacetic acid Natural products NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-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
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 125000001544 thienyl group Chemical group 0.000 description 5
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 4
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 3
- QIOZLISABUUKJY-UHFFFAOYSA-N Thiobenzamide Chemical compound NC(=S)C1=CC=CC=C1 QIOZLISABUUKJY-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 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
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 150000003936 benzamides Chemical class 0.000 description 2
- 239000002027 dichloromethane extract Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- RDRCCJPEJDWSRJ-UHFFFAOYSA-N pyridine;1h-pyrrole Chemical compound C=1C=CNC=1.C1=CC=NC=C1 RDRCCJPEJDWSRJ-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- QYZLKGVUSQXAMU-UHFFFAOYSA-N penta-1,4-diene Chemical group C=CCC=C QYZLKGVUSQXAMU-UHFFFAOYSA-N 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- WPZSAUFQHYFIPG-UHFFFAOYSA-N propanethioamide Chemical compound CCC(N)=S WPZSAUFQHYFIPG-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003556 thioamides Chemical class 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
Landscapes
- 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 kind of synthetic methods of N- (3- (dimethyl amido) -3- rosickyite acyl group)-benzamide (I) replaced; by benzoyl allylamine (II), sulphur and the N replaced; dinethylformamide (DMF) is in catalyst or in the presence of without catalyst; it is directly made by the vulcanization for the ethylene linkage end position carbon being connected with saturated carbon atom, amination, reaction equation are as follows:；Substituted benzoyl allylamine (II), wherein R1~R5For identical or different hydrogen, alkyl, halogenated alkyl, aryl, halogen, nitro, sulphur carboxyl, carboxyl, ester group, cyano.The substituted benzoyl allylamine (II) that the present invention is easy to get with market quickly and easily obtains the benzamide (I) of N- (3- (dimethyl amido) -3- rosickyite acyl group)-substitution by single step reaction for starting material.Reaction process of the invention is novel, convenient, and reaction condition is mildly easily-controllable, and reaction dissolvent system is simple, easy post-processing.
Description
Technical field
The present invention relates to the intermediate synthetic method of a kind of chemical industry, medicine and pesticide, specially a kind of N- (3- (dimethyl
Amido) -3- rosickyite acyl group)-replace benzamide (I) new synthetic method.
Background technique
The benzamide (I) that N- (3- (dimethyl amido) -3- rosickyite acyl group)-replaces is the important chemical industry of one kind, medicine
And pesticide intermediate, however the problems such as traditional synthetic method step is more, and raw material is rare, severe reaction conditions, limit it has
The acquisition of effect.
Document Organic Letters, 2014,16 (1), 310-313 and Organic Letters, 2018,
20 (8), 2228-2231 individually disclose the method for synthesizing thio phenyl acetamide and thiobenzamide using phenylacetylene；
Organic & Biomolecular Chemistry, 12 (4), 700-707, which is reported, synthesizes sulphur using phenylacetylene halide
For the method for phenyl acetamide；Organic Letters, 2014,16 (14), 3624-3627 and Tetrahedron, 2016,
72 (16), 2012-2017 report the side using phenylacetic acid or cinnamic acid synthesis thiobenzamide and thio phenyl acetamide
Method；ChemistrySelect, 2017,2 (20), 5532-5535 report thio using acetophenone and its derivative synthesis
The method of phenyl acetamide；Advanced Synthesis & Catalysis, 2017,359 (24), 4300-4304 and
Synthesis, 1989, (3), 202-204 reports the side for synthesizing thio phenyl acetamide in acid condition using styrene
Method；
Above is referred to synthetic method have the obvious disadvantage that: 1) the involved acetylene bond for participating in reaction and ethylene linkage are all total with aromatic ring
The acetylene bond and ethylene linkage of yoke, to the acetylene bond and ethylene linkage not being conjugated, without any information or hint；2) it is participated in by acetylene bond and ethylene linkage
Reaction only generates thio phenyl acetamide and thiobenzamide, and can not generate thiopropionamide.3) using acetophenone and its spread out
The method of the thio phenyl acetamide of biosynthesis cannot be directly used to the synthesis of benzamido thiopropionamide (I).
Therefore it provides a kind of mild synthesis easily-controllable, reaction system is simple, reaction step is few, raw material is easy to get of reaction condition
Method is necessary.
Summary of the invention
In order to overcome the deficiencies in the prior art described above, the present invention provides a kind of convenient, reaction condition is mildly easily-controllable, anti-
The benzene first for answering the synthesis N- (3- (dimethyl amido) -3- rosickyite acyl group)-that system is simple, reaction step is few, raw material is easy to get to replace
The synthetic method of amide (I).
The object of the present invention is achieved like this:
A kind of synthetic method for the benzamide (I) that N- (3- (dimethyl amido) -3- rosickyite acyl group)-replaces, by the benzene replaced
Formyl allylamine (II), sulphur (S) and N,N-dimethylformamide (DMF) are in catalyst or pass through one in the presence of without catalyst
It walks reaction process to be directly made, reaction equation are as follows:
；
The synthetic method for the benzamide (I) that the N- (3- (dimethyl amido) -3- rosickyite acyl group)-replaces, by with it is full
Vulcanization, the amination for the ethylene linkage end position carbon being connected with carbon atom, the rosickyite amide functional group replaced to regioselectivity, in turn
It is readily synthesized the benzamide (I) of N- (3- (dimethyl amido) -3- rosickyite acyl group)-substitution；
The substituted benzoyl allylamine (II), wherein R1~R5For identical or different hydrogen, alkyl, halogenated alkyl, aryl,
Halogen, nitro, sulphur carboxyl, carboxyl, ester group, cyano；
It is reactant that the N,N-dimethylformamide (DMF) that the reaction uses is reaction dissolvent again.
The catalyst is alkali carbonate, including potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate；Alkali metal hydrogen-oxygen
Compound includes sodium hydroxide, potassium hydroxide, lithium hydroxide and cesium hydroxide；Organic base includes triethylamine, triethylene diamine and pyrrole
Pyridine.
The molar ratio of the substituted benzoyl allylamine (II) and sulphur is 1 ︰ 1 ~ 10；
The molar ratio of the substituted benzoyl allylamine (II) and catalyst is 1 ︰ 0 ~ 5；
The molar ratio of the substituted benzoyl allylamine (II) and reaction dissolvent is 1 ︰ 20-50；
Feeding mode is to put into the benzoyl allylamine (II) replaced and sulphur in N,N-dimethylformamide (DMF)；
The reaction time is 1 ~ 20 hour, and reaction temperature is 60 ~ 150oC。
The reaction process of the benzamide (I) for preparing N- (3- (dimethyl amido) -3- rosickyite acyl group)-substitution
Post-processing approach are as follows: temperature of reaction system is cooled to room temperature filtering after reaction, removes excessive sulphur and catalyst, and filtrate is negative
Pressure steams excessive n,N-Dimethylformamide (DMF), extracts, is concentrated after residue washing, and recrystallization or silica gel column chromatography are
Obtain the benzamide (I) of pure N- (3- (dimethyl amido) -3- rosickyite acyl group)-substitution.
A kind of positive beneficial effect: chemical intermediate N- (3- (dimethyl amido) -3- rosickyite acyl group)-disclosed by the invention
The novel synthesis of substituted benzamide (I), the substituted benzoyl allylamine (II) being easy to get with market is starting material, warp
It crosses single step reaction and conveniently and efficiently obtains purpose product.The sulphur that this method passes through the ethylene linkage end position carbon being connected with saturated carbon atom
Change, amination, the rosickyite amide functional group replaced to regioselectivity, is N- (3- (dimethyl amido) -3- rosickyite acyl group) -
The synthesis and acquisition of substituted benzamide (I) provide a kind of convenient and fast route of synthesis.It was reacted involved by the synthetic method
Cheng Xinying is convenient, and reaction condition is mildly easily-controllable, and reaction dissolvent system is simple, easy post-processing.
Specific embodiment
Combined with specific embodiments below, the present invention is described further:
A kind of synthetic method for the benzamide (I) that N- (3- (dimethyl amido) -3- rosickyite acyl group)-replaces, by the benzene replaced
Formyl allylamine (II), sulphur (S) and N,N-dimethylformamide (DMF) are in catalyst or pass through one in the presence of without catalyst
It walks reaction process to be directly made, reaction equation are as follows:
；
This synthetic method is completely newly by vulcanization, the amination of the ethylene linkage end that is connected with saturated carbon atom position carbon, regioselectivity
The rosickyite amide functional group replaced, and then it is readily synthesized the benzene of N- (3- (dimethyl amido) -3- rosickyite acyl group)-substitution
Formamide (I).
The substituted benzoyl allylamine (II), R1~R5For identical or different hydrogen, alkyl, halogenated alkyl, aryl,
Halogen, nitro, sulphur carboxyl, carboxyl, ester group and cyano.
It is reactant that the N,N-dimethylformamide (DMF) that the reaction uses is reaction dissolvent again.
The catalyst is alkali carbonate, including potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate；Alkali metal hydrogen-oxygen
Compound includes sodium hydroxide, potassium hydroxide, lithium hydroxide and cesium hydroxide；Organic base includes triethylamine, triethylene diamine and pyrrole
Pyridine.
The molar ratio of the substituted benzoyl allylamine (II) and sulphur is 1 ︰ 1 ~ 10；
The molar ratio of the substituted benzoyl allylamine (II) and catalyst is 1 ︰ 0 ~ 5；
The molar ratio of the substituted benzoyl allylamine (II) and reaction dissolvent is 1:20-50；
Feeding mode is that the sulphur of the benzoyl allylamine (II) replaced and calculation amount is put into an appropriate number of N, N- dimethyl
In formamide (DMF)；
The reaction process of the benzamide (I) for preparing N- (3- (dimethyl amido) -3- rosickyite acyl group)-substitution, reaction
Time is 1 ~ 20 hour, and reaction temperature is 60 ~ 150oC。
The reaction process of the benzamide (I) for preparing N- (3- (dimethyl amido) -3- rosickyite acyl group)-substitution
Post-processing approach are as follows: temperature of reaction system is cooled to room temperature filtering after reaction, and negative pressure steams excessive N, N- dimethyl methyl
Amide (DMF) is extracted after residue washing, is concentrated, and recrystallization or silica gel column chromatography obtain pure N- (3- (dimethyl amine
Base) -3- rosickyite acyl group)-replace benzamide (I).
Embodiment 1
The synthesis of N- (3- (dimethyl amido) -3- rosickyite acyl group)-benzamide
By benzoyl allyl amine (1.61 g, 10 mmol) addition fill n,N-Dimethylformamide (DMF) (16 g, 0.22
Mol) three mouthfuls of reaction flasks in, while sulphur (1.6 g, 50 mmol) are added, are in atmospheric conditions gradually raised to temperature
120oC reacts 12 hours, and the conversion of tlc analysis reactant is complete.Then temperature of charge is dropped into room temperature, filters, removed
The sulphur of amount.Filtrate deviates from a large amount of solvent under vacuum, and raffinate is washed with water, methylene chloride extraction.Dichloromethane extract is dry
Concentration, residue are separated with silica gel column chromatography, obtain N- (3- (dimethyl amido) -3- rosickyite acyl group)-benzamide 1.44g, are received
Rate 61%.
1H NMR (400MHz, CDCl3) δ: 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) δ: 201.0, 167.2, 134.4, 131.5,
128.5, 127.0, 44.6, 41.6, 41.3, 38.0。HPLC-MS m/z: 259.0872 [M+Na]+。
Embodiment 2
The chloro- N- of 2- (3- (dimethyl amido) -3- rosickyite acyl group) -6- (1 hydrogen -1,2,4- triazol-1-yl) benzamide
Synthesis
The chloro- 6- of N- allyl -2- (1 hydrogen -1,2,4- triazol-1-yl) benzamide (2.6 g, 10 mmol) addition is filled
In three mouthfuls of reaction flasks of n,N-Dimethylformamide (DMF) (26 g, 0.35 mol), while sulphur (2.6 g, 80 mmol) are added,
K2CO3(2.8 g, 20 mmol), are gradually raised to 110 for temperature in atmospheric conditionsoC reacts 15 hours, tlc analysis reaction
Object conversion is complete.Then temperature of charge is dropped into room temperature, filters, removes excessive sulphur and potassium carbonate.Filtrate takes off under vacuum
A large amount of solvent, raffinate are washed with water out, methylene chloride extraction.The dry concentration of dichloromethane extract, residue silica gel column layer
Analysis separation, obtains the chloro- N- of 2- (3- (dimethyl amido) -3- rosickyite acyl group) -6- (1 hydrogen -1,2,4- triazol-1-yl) benzamide
2.2 g, yield 65%.
1H NMR (400MHz, CDCl3) δ: 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) δ: 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-MS m/z: 360.0664 [M+Na]+。
The substituted benzoyl allylamine (II) that the present invention is easy to get with market is starting material, in sulphur, DMF and catalyst
In the presence of, the benzamide product (I) of N- (3- (dimethyl amido) -3- rosickyite acyl group)-substitution is obtained by single step reaction.It should
Method is converted into thioamides Guan Nengtuan by vulcanization, the amination of allyl ethylene linkage end position carbon, and then is N- (3- (diformazan
Base amido) -3- rosickyite acyl group)-the acquisition of benzamide (I) product that replaces provides a kind of convenient and fast route of synthesis.The conjunction
Novel, simple, convenient at reaction process involved by method, reaction condition is mildly easily-controllable, reaction dissolvent system is simple, post-processing side
Just etc..
The above case study on implementation is merely to illustrate the preferred embodiment of the present invention, but the present invention is not limited to above-mentioned embodiment party
Formula, the field those of ordinary skill within the scope of knowledge, it is made any within the spirit and principles in the present invention
Modification, equivalent substitute and improvement etc., are regarded as the protection scope of the application.
Claims (7)
1. a kind of synthetic method for the benzamide (I) that N- (3- (dimethyl amido) -3- rosickyite acyl group)-replaces, feature exist
In: by the benzoyl allylamine (II), sulphur and the n,N-Dimethylformamide that replace in catalyst or in the presence of without catalyst,
By vulcanization, the amination of the ethylene linkage end position carbon being connected with saturated carbon atom, the rosickyite amide official replaced to regioselectivity
It can roll into a ball, and then be readily synthesized the benzamide (I) of N- (3- (dimethyl amido) -3- rosickyite acyl group)-substitution, reaction equation are as follows:
；
The substituted benzoyl allylamine (II), wherein R1~R5For identical or different hydrogen, alkyl, halogenated alkyl, aryl, halogen
Element, nitro, sulphur carboxyl, carboxyl, ester group, cyano.
2. the benzamide (I) that a kind of N- (3- (dimethyl amido) -3- rosickyite acyl group)-according to claim 1 replaces
Synthetic method, it is characterised in that: the molar ratio of the substituted benzoyl allylamine (II) and sulphur is 1 ︰ 1 ~ 10.
3. the benzamide (I) that a kind of N- (3- (dimethyl amido) -3- rosickyite acyl group)-according to claim 1 replaces
Synthetic method, it is characterised in that: it is also reaction dissolvent that the n,N-Dimethylformamide (DMF), which is reactant, described
The molar ratio of substituted benzoyl allylamine (II) and n,N-Dimethylformamide (DMF) is 1:20-50.
4. the benzamide (I) that a kind of N- (3- (dimethyl amido) -3- rosickyite acyl group)-according to claim 1 replaces
Synthetic method, it is characterised in that: the catalyst is alkali carbonate, including potassium carbonate, sodium carbonate, cesium carbonate and carbon
Sour lithium；Alkali metal hydroxide includes sodium hydroxide, potassium hydroxide, lithium hydroxide and cesium hydroxide；Organic base include triethylamine,
Triethylene diamine and pyridine.
5. the benzamide that a kind of N- (3- (dimethyl amido) -3- rosickyite acyl group)-according to claim 1 or 4 replaces
(I) synthetic method, it is characterised in that: 1 ︰ 0 ~ 5 of molar ratio of the substituted benzoyl allylamine (II) and catalyst.
6. the benzene first that a kind of described in any item N- (3- (dimethyl amido) -3- rosickyite acyl group)-replace according to claim 1 ~ 5
The synthetic method of amide (I), it is characterised in that: the reaction process, the reaction time be 1 ~ 20 hour, reaction temperature be 60 ~
150oC。
7. the benzene first that a kind of described in any item N- (3- (dimethyl amido) -3- rosickyite acyl group)-replace according to claim 1 ~ 6
The synthetic method of amide (I), it is characterised in that: the post-processing approach of the reaction process are as follows: reaction system after reaction
Temperature is cooled to room temperature filtering, and negative pressure steams excessive n,N-Dimethylformamide (DMF), extracts after residue washing, dense
Contracting, recrystallization or column chromatograph to obtain the benzamide (I) of N- (3- (dimethyl amido) -3- rosickyite acyl group)-substitution.
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