CN116396180A - Preparation method of formamide compound - Google Patents
Preparation method of formamide compound Download PDFInfo
- Publication number
- CN116396180A CN116396180A CN202310393751.3A CN202310393751A CN116396180A CN 116396180 A CN116396180 A CN 116396180A CN 202310393751 A CN202310393751 A CN 202310393751A CN 116396180 A CN116396180 A CN 116396180A
- Authority
- CN
- China
- Prior art keywords
- compound
- reaction
- amine
- preparation
- formamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- -1 formamide compound Chemical class 0.000 title claims abstract description 41
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000010949 copper Substances 0.000 claims abstract description 13
- 229910052802 copper Inorganic materials 0.000 claims abstract description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 47
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 238000004440 column chromatography Methods 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 150000003141 primary amines Chemical class 0.000 claims description 6
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 150000003335 secondary amines Chemical class 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 150000001412 amines Chemical class 0.000 abstract description 7
- 239000000758 substrate Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 6
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 5
- 239000011259 mixed solution Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 238000007789 sealing Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 2
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
- 239000003377 acid catalyst Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- XCEYKKJMLOFDSS-UHFFFAOYSA-N 4-chloro-n-methylaniline Chemical compound CNC1=CC=C(Cl)C=C1 XCEYKKJMLOFDSS-UHFFFAOYSA-N 0.000 description 1
- JFXDIXYFXDOZIT-UHFFFAOYSA-N 4-methoxy-n-methylaniline Chemical compound CNC1=CC=C(OC)C=C1 JFXDIXYFXDOZIT-UHFFFAOYSA-N 0.000 description 1
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical class NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000005937 allylation reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 150000008363 butyronitriles Chemical class 0.000 description 1
- 230000021235 carbamoylation Effects 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of a formamide compound, which comprises the following steps: copper trifluoromethyl compound is used as trifluoromethyl source and reacts with amine compound to obtain the formamide compound. The invention uses cheap and easily available amine as a substrate and prepares the formamide compound with a specific high-valence copper trifluoromethyl compound efficiently and simply, and the method has the characteristics of low cost, good selectivity, wide substrate range, simple operation, environmental protection and the like, and is very expected to carry out large-scale industrial production.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and relates to a preparation method of a formamide compound.
Background
The process of converting an amine to formamide is interesting due to the many uses of formamide as a synthetic intermediate. These include stoichiometric reactions of formylating reagents and catalytic reactions with CO as a carbon-based source. Formamide is an important class of compounds as an intermediate in the synthesis of bactericides and pharmaceuticals, and the formation of isocyanates, formamidines and butyronitriles. Formamide can also be used as a reagent for functional group conversion, wilsmei diformylation, allylation of carbon-based compounds and hydrogenation. Because of its wide range of applications, a number of methods have been developed to synthesize formamide.
Current methods of preparing formamide include the use of stoichiometric formylating agents, acid catalysts, organic catalysts, transition metal catalysts, and catalytic carbonization reactions. Both the acid catalyst and the organic catalyst can produce formamide with formic acid and formate. The metal catalyst may formate the amine with formic acid, paraformaldehyde, formaldehyde and methanol as the source of formyl groups. Catalytic carbosylation pathways produce formamide from CO in the presence of ionic liquids, transition metals, or oxidants. Base-mediated CO glycosylation has also been reported. These methods are applicable to a wide range of amines, such as primary, cyclic and acyclic secondary, sterically hindered, aromatic, amino acids and amino acid esters. The process can be used to formylate amines and maintain the purity of the enantiomer. Although formylation chemistry has a long history, there is room for development in new catalytic processes.
In the above reaction, a transition metal catalyst or a catalytic condition is generally required to be complicated, so how to simply and efficiently achieve carbamylation under mild conditions is an important research in the art.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a preparation method of a formamide compound. The method belongs to a one-pot method and has the characteristics of simple and efficient reaction, low cost, simple operation and the like.
To achieve the purpose, the invention adopts the following technical scheme:
in one aspect, the present invention provides a method for preparing a carboxamide compound, the method comprising the steps of:
copper trifluoromethyl compound is used as trifluoromethyl source and reacts with amine compound to obtain the formamide compound.
In the present invention, the copper trifluoromethyl compound includes a compound having the following structure,
in the present invention, the amine compound includes a primary amine and a secondary amine.
Preferably, the structural formula of the amine compound is R-NH 2 Or (b)
Wherein Ar is selected from the group consisting of unsubstituted or substituted aryl; the substituent comprises any one or a combination of at least two of alkyl, alkoxy, halogen or phenyl; wherein R and R 1 Each independently selected from unsubstituted or substituted aryl; the substituents include alkyl and/or phenyl.
In the present invention, the aryl group is selected from C6-C18 aryl groups, such as C6, C7, C8, C10, C12, C15 or C18 aryl groups, such as phenyl, biphenyl, naphthyl, anthracenyl, and the like.
In the present invention, the alkyl group is preferably a C1-C5 alkyl group, for example, a C1, C2, C3, C4 or C5 alkyl group. The alkoxy group is preferably a C1-C5 alkoxy group, such as a C1, C2, C3, C4 or C5 alkoxy group.
In the present invention, the halogen is F, cl, br or I.
Preferably, the amine compound is selected from
Preferably, the molar ratio of amine compound to copper trifluoromethyl compound is from 1:1 to 1:1.3, for example 1:1, 1:1.1, 1:1.2 or 1:1.3.
In the invention, the synthetic route of the preparation method is as follows:
wherein Ar, R and R 1 Is the same as defined above.
Preferably, the amine compound is a primary amine, and the reaction is performed in the presence of an acidic substance selected from any one or a combination of at least two of trifluoroacetic acid, hydrochloric acid, sulfuric acid or phosphoric acid, and the acidic substance is preferably trifluoroacetic acid.
In the present invention, when the amine compound is a secondary amine, the reaction process can be completed in a solvent without any additives.
Preferably, the molar ratio of amine compound to acidic species is from 1:1 to 1:1.3, for example 1:1, 1:1.1, 1:1.2 or 1:1.3.
Preferably, the reaction is carried out in an organic solvent selected from any one or a combination of at least two of N, N-Dimethylformamide (DMF), 1, 4-dioxane, dimethyl sulfoxide (DMSO), dichloroethane (DCE), N-methylpyrrolidone (NMP), anhydrous N, N-dimethylacetamide (dry DMA), toluene, tetrahydrofuran or acetonitrile (MeCN).
Preferably, the temperature of the reaction is 80-100 ℃ (e.g. 80 ℃, 85 ℃, 90 ℃, 95 ℃ or 100 ℃) and the reaction time is 6-12 hours (e.g. 6 hours, 8 hours, 10 hours, 11 hours or 12 hours).
In the invention, after the reaction is completed, the reaction system is cooled to room temperature, dichloromethane is added for dilution and filtration, and finally silica gel spin-dry column chromatography is added to obtain the target product.
Compared with the prior art, the invention has the following beneficial effects:
the invention takes cheap and easily available amine (including primary amine and secondary amine) as a substrate, and prepares the formamide compound with specific high-valence copper trifluoromethyl compound efficiently and simply. In addition, the formamide is considered as a raw material for synthesizing medicines, fragrances, dyes and the like, and the method has the characteristics of wide application in the aspect of synthesis, low cost, good selectivity, wide substrate range, simplicity in operation, environment friendliness and the like, and is very expected to carry out large-scale industrial production.
Detailed Description
The technical scheme of the invention is further described by the following specific embodiments. It will be apparent to those skilled in the art that the examples are merely to aid in understanding the invention and are not to be construed as a specific limitation thereof.
In the following examples (phen) Cu III (CF 3 ) 3 Representative of
Example 1
After placing a stirrer in a 25mL Schlenk tube, the (phen) Cu was added III (CF 3 ) 3 (1) (90 mg,0.2mmol,1 equiv) the nozzle was sealed with a rubber stopper and sealing film, and three more repeated vacuum and nitrogen fills were performed. N-methylaniline (22 mg,0.2mmol,1 equiv) was mixed with 2mL of 1, 4-dioxane, and the mixture was slowly added to the reaction tube by syringe, and the reaction was stirred in an oil bath at 100deg.C for 12 hours. After the reaction, the reaction tube was cooled to room temperature, and then the mixed solution was post-treated, and the reaction solution was diluted with an appropriate amount of dichloromethane, filtered, and subjected to column chromatography on a small amount of silica gel, to give a yellow oily liquid 3a (yield 88%).
The reaction process of the steps is shown as follows:
the nuclear magnetic data of product 3a are as follows:
1 H NMR(400MHz,CDCl 3 )δ8.48(s,1H),7.42(t,J＝7.9Hz,2H),7.28(t,J＝7.4Hz,1H),7.20–7.15(m,2H),3.32(s,3H)。
13 C NMR(101MHz,CDCl 3 )δ162.3,142.1,129.6,126.3,122.3,32.0。
example 2
At 25mL SAdding stirring rod into the chlenk tube, adding (phen) Cu III (CF 3 ) 3 (1) (90 mg,0.2mmol,1 equiv) the nozzle was sealed with a rubber stopper and sealing film, and three more repeated vacuum and nitrogen fills were performed. N-methyl-4-methoxyaniline (28 mg,0.2mmol,1 equiv) was mixed with 2mL of 1, 4-dioxane, and the mixture was slowly added to the reaction tube via syringe, and reacted in an oil bath at 100℃under stirring for 12 hours. After the reaction, the reaction tube was cooled to room temperature, and then the mixed solution was post-treated, and the reaction solution was diluted with an appropriate amount of dichloromethane, filtered, and subjected to column chromatography by spin-drying with a small amount of silica gel to give a yellowish brown oily liquid 3b (yield 95%).
The reaction process of the steps is shown as follows:
the nuclear magnetic data of product 3b are as follows:
1 H NMR(400MHz,CDCl 3 )δ8.49(s,1H),7.25(d,J＝9.0Hz,2H),7.08(d,J＝8.9Hz,2H),3.97(s,3H),3.42(s,3H)。
13 C NMR(101MHz,CDCl 3 )δ162.3,158.2,135.1,124.5,114.6,55.4,32.5。
example 3
After placing a stirrer in a 25mL Schlenk tube, the (phen) Cu was added III (CF 3 ) 3 (1) (90 mg,0.2mmol,1 equiv) the nozzle was sealed with a rubber stopper and sealing film, and three more repeated vacuum and nitrogen fills were performed. 4-chloro-N-methylaniline (29 mg,0.2mmol,1 equiv) was mixed with 2mL of 1, 4-dioxane, and the mixture was slowly added to the reaction tube by syringe, and reacted in an oil bath at 100℃under stirring for 12 hours. After the reaction, the reaction tube was cooled to room temperature, and then the mixed solution was post-treated, and the reaction solution was diluted with an appropriate amount of dichloromethane, filtered, and subjected to column chromatography on a small amount of silica gel, to give a tan solid 3c (yield 95%).
The reaction process of the steps is shown as follows:
the nuclear magnetic data of product 3c are as follows:
1 H NMR(400MHz,CDCl 3 )δ8.43(s,1H),7.37(d,J＝8.8Hz,2H),7.10(d,J＝8.8Hz,2H),3.28(s,3H).。
13 C NMR(101MHz,CDCl 3 )δ162.0,140.7,132.0,129.7,123.5,32.0.。
example 4
After placing a stirrer in a 25mL Schlenk tube, the (phen) Cu was added III (CF 3 ) 3 (1) (90 mg,0.2mmol,1 equiv) the nozzle was sealed with a rubber stopper and sealing film, and three more repeated vacuum and nitrogen fills were performed. Aniline (19 mg,0.2mmol,1 equiv) and trifluoroacetic acid (23 mg,0.2mmol,1 equiv) were mixed with 2mL of acetonitrile and then slowly added to the reaction tube by syringe, and the reaction was stirred in an oil bath at 100℃for 12 hours. After the reaction, the reaction tube was cooled to room temperature, and then the mixed solution was post-treated, and the reaction solution was diluted with an appropriate amount of dichloromethane, filtered, and subjected to column chromatography on a small amount of silica gel, to give a yellow oily liquid 3d (yield 54%).
The reaction process of the steps is shown as follows:
the nuclear magnetic data of product 3d are as follows:
1 H NMR(400MHz,CDCl 3 )δ8.71(d,J＝9.2Hz,1H),8.45(br s,1H),8.37(s,1H),7.55(d,J＝7.9Hz,2H),7.39–7.30(m,4H),7.19(t,J＝7.4Hz,1H),7.14(t,J＝7.4Hz,1H),7.10(d,J＝7.7Hz,2H)。
13 C NMR(101MHz,CDCl 3 )δ162.7,159.1,136.8,136.7,129.7,129.1,125.3,124.8,120.0,118.8。
example 5
Put in 25mL Schlenk tubeAdding (phen) Cu after stirring III (CF 3 ) 3 (1) (90 mg,0.2mmol,1 equiv) the nozzle was sealed with a rubber stopper and sealing film, and three more repeated vacuum and nitrogen fills were performed. P-methoxyaniline (25 mg,0.2mmol,1 equiv) and trifluoroacetic acid (23 mg,0.2mmol,1 equiv) were mixed with 2mL of acetonitrile and then slowly added to the reaction tube by syringe, and reacted in an oil bath at 100℃for 12 hours with stirring. After the reaction, the reaction tube was cooled to room temperature, and then the mixed solution was post-treated, and the reaction solution was diluted with an appropriate amount of dichloromethane, filtered, and subjected to column chromatography on a small amount of silica gel, to give a brown oily liquid 3e (yield 47%).
The reaction process of the steps is shown as follows:
the nuclear magnetic data of product 3e are as follows:
1 H NMR(400MHz,CDCl 3 )δ8.52(br s,1H),8.31(s,1H),8.13(br s,1H),7.44(d,J＝8.8Hz,2H),7.03(d,J＝8.8Hz,2H),6.87(m,4H),3.80(s,3H),3.78(s,3H)。
13 C NMR(101MHz,CDCl 3 )δ163.1,158.9,157.6,156.7,129.9,129.5,121.8,121.6,114.9,114.2,55.5,55.4。
example 6: screening of reaction conditions
Referring to example 1, different reaction conditions were replaced to give the corresponding product. The specific reaction process is as follows:
the specific results are shown in Table 1.
TABLE 1 Synthesis results of different reactions
Wherein, the yields are all separation yields; wherein the material dosage of the raw material compounds is as follows: 1 (0.2 mmol), 2a (0.2 mmol). Wherein item 7 is example 1.
As can be seen from Table 1, when the amine is primary amine, trifluoroacetic acid is selected as the additive, and acetonitrile is used as the solvent, the selectivity and yield of the target product are both good; when the amine is secondary amine, the selectivity and the yield of the target product are good when the 1, 4-dioxane is selected as a solvent.
The applicant states that the present invention describes the preparation method of the carboxamide compound of the present invention by the above examples, but the present invention is not limited to the above examples, i.e. it does not mean that the present invention must be practiced by relying on the above examples. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of raw materials for the product of the present invention, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present invention and the scope of disclosure.
Claims (10)
1. A process for the preparation of a carboxamide compound, comprising the steps of:
copper trifluoromethyl compound is used as trifluoromethyl source and reacts with amine compound to obtain the formamide compound.
2. The method of preparing according to claim 1, wherein the copper trifluoromethyl compound comprises a compound of the structure:
3. the production method according to claim 1 or 2, wherein the amine compound comprises a primary amine and a secondary amine;
preferably, the amine compound has the structural formula of or
Wherein Ar is selected from the group consisting of unsubstituted or substituted aryl; the substituent comprises any one or a combination of at least two of alkyl, alkoxy, halogen or phenyl; r and R 1 Each independently selected from unsubstituted or substituted aryl; the substituents include alkyl and/or phenyl.
4. A method of preparation according to claim 3, wherein the aryl is selected from C6-C18 aryl;
preferably, the alkyl group is preferably a C1-C5 alkyl group;
preferably, the alkoxy group is preferably a C1-C5 alkoxy group.
5. The method according to claim 3 or 4, wherein the amine compound is selected from the group consisting of
6. The method according to any one of claims 1 to 5, wherein the amine compound is a primary amine, and the reaction is carried out in the presence of an acidic substance selected from any one or a combination of at least two of trifluoroacetic acid, hydrochloric acid, sulfuric acid, and phosphoric acid, and the acidic substance is preferably trifluoroacetic acid.
7. The method according to any one of claims 1 to 6, wherein the molar ratio of the amine compound to the copper trifluoromethyl compound is 1:1 to 1:1.3.
8. The preparation method according to any one of claims 1 to 7, wherein the reaction is performed in an organic solvent selected from any one or a combination of at least two of N, N-dimethylformamide, 1, 4-dioxane, dimethyl sulfoxide, dichloroethane, N-methylpyrrolidone, anhydrous N, N-dimethylacetamide, toluene, tetrahydrofuran, or acetonitrile.
9. The process according to any one of claims 1 to 8, wherein the reaction is carried out at a temperature of 80 to 100 ℃ for a reaction time of 6 to 12 hours.
10. The preparation method according to any one of claims 1 to 9, wherein after the reaction is completed, the reaction system is cooled to room temperature, diluted and filtered by adding dichloromethane, and finally the target product formamide compound is obtained by adding silica gel spin-dry column chromatography.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310393751.3A CN116396180A (en) | 2023-04-13 | 2023-04-13 | Preparation method of formamide compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310393751.3A CN116396180A (en) | 2023-04-13 | 2023-04-13 | Preparation method of formamide compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116396180A true CN116396180A (en) | 2023-07-07 |
Family
ID=87015706
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310393751.3A Pending CN116396180A (en) | 2023-04-13 | 2023-04-13 | Preparation method of formamide compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116396180A (en) |
-
2023
- 2023-04-13 CN CN202310393751.3A patent/CN116396180A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101952298B (en) | Ligands for transition-metal-catalyzed cross-couplings, and methods of use thereof | |
| DE60131985T2 (en) | CATALYST FOR AROMATIC C-O, C-N AND C-C BINDING | |
| CN108640869B (en) | Transition metal catalyzed C-H coupling high-efficiency preparation of o-amidated aryl heterocyclic derivatives | |
| CN108380245B (en) | Bidentate phosphorus-aza-carbene p-cymene type ruthenium complex catalyst, preparation method and synthesis application thereof | |
| CN110105305B (en) | Transition metal catalyzed C-H activation/cyclization synthesis 1,2-benzothiazine derivative green synthesis method | |
| CN111675662A (en) | Preparation method of 2-trifluoromethyl substituted quinazolinone compound | |
| CN110041235B (en) | N-phenyl-N-p-toluenesulfonyl trifluoroacetamide and application thereof | |
| CN111233617A (en) | Synthesis method of 1-iodoalkyne compound | |
| CN111484396A (en) | Method for denitration of nitroaromatic hydrocarbon by transition metal catalysis | |
| CN112375105B (en) | Application of N, N-coordinated divalent nickel complex containing meta-carborane ligand | |
| CN106008265B (en) | A kind of method of palladium chtalyst benzyl quaternary ammonium salt C-N key fracture Suzuki coupling | |
| CN111116416B (en) | Preparation method of beta-amino acrylonitrile compound | |
| CN116396180A (en) | Preparation method of formamide compound | |
| CN113336665B (en) | Preparation method of bromobenzene para-aminated compound mediated by high-valence iodine reagent | |
| CN111229312B (en) | Solvent-free catalyst and preparation method and application thereof | |
| CN114989178A (en) | Spiro [ beta-lactam-3, 3' -oxindole ] derivative and preparation method and application thereof | |
| CN107353217B (en) | Preparation method of anthranilate and amide compound | |
| CN113443950A (en) | Method for reducing carbonyl into methylene under illumination | |
| CN111517903B (en) | Aromatic C-NO catalyzed by transition metal 2 Hiyama coupling method of | |
| CN110003062B (en) | N-phenyl-N-p-toluenesulfonyl difluoroacetamide and application thereof | |
| KR101522464B1 (en) | New process for the production of arensulfonyl chloride from arensulfonic acid | |
| CN113402361B (en) | Gem difluoro vinyl transfer reagent and preparation method thereof | |
| CN111440052B (en) | Stille coupling method for aromatic nitro compound catalyzed by transition metal | |
| CN115197124B (en) | Method for synthesizing polysubstituted pyridine derivative based on alpha, beta-unsaturated oxime ester under catalysis of ammonium iodide | |
| CN112538045B (en) | Method for synthesizing quinoline derivative by copper catalysis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |