CN113292443B - Process for producing amides - Google Patents
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- CN113292443B CN113292443B CN202011330372.2A CN202011330372A CN113292443B CN 113292443 B CN113292443 B CN 113292443B CN 202011330372 A CN202011330372 A CN 202011330372A CN 113292443 B CN113292443 B CN 113292443B
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- 150000001408 amides Chemical class 0.000 title claims abstract description 44
- 238000000034 method Methods 0.000 title claims abstract description 30
- 230000008569 process Effects 0.000 title claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 56
- 238000002360 preparation method Methods 0.000 claims abstract description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
- 239000001301 oxygen Substances 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- -1 compound amide Chemical class 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 11
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 9
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 239000012298 atmosphere Substances 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 150000002540 isothiocyanates Chemical class 0.000 abstract description 9
- 239000003054 catalyst Substances 0.000 abstract description 7
- 230000009471 action Effects 0.000 abstract description 6
- 229910052751 metal Inorganic materials 0.000 abstract description 5
- 239000002184 metal Substances 0.000 abstract description 5
- 239000003999 initiator Substances 0.000 abstract description 4
- 239000012948 isocyanate Substances 0.000 abstract description 4
- 150000002513 isocyanates Chemical class 0.000 abstract description 4
- 239000012190 activator Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000009467 reduction Effects 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 2
- 150000003948 formamides Chemical class 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 88
- 238000003786 synthesis reaction Methods 0.000 description 26
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 24
- 230000015572 biosynthetic process Effects 0.000 description 24
- 239000007787 solid Substances 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 12
- 238000005859 coupling reaction Methods 0.000 description 11
- UNNGUFMVYQJGTD-UHFFFAOYSA-N 2-Ethylbutanal Chemical compound CCC(CC)C=O UNNGUFMVYQJGTD-UHFFFAOYSA-N 0.000 description 9
- 150000001299 aldehydes Chemical class 0.000 description 9
- ABQKHKWXTUVKGF-UHFFFAOYSA-N 1-isothiocyanato-4-methylbenzene Chemical compound CC1=CC=C(N=C=S)C=C1 ABQKHKWXTUVKGF-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 229940117953 phenylisothiocyanate Drugs 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000002955 isolation Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- LGYNIFWIKSEESD-UHFFFAOYSA-N 2-ethylhexanal Chemical compound CCCCC(CC)C=O LGYNIFWIKSEESD-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- FTZILAQGHINQQR-UHFFFAOYSA-N 2-Methylpentanal Chemical compound CCCC(C)C=O FTZILAQGHINQQR-UHFFFAOYSA-N 0.000 description 2
- BYGQBDHUGHBGMD-UHFFFAOYSA-N 2-methylbutanal Chemical compound CCC(C)C=O BYGQBDHUGHBGMD-UHFFFAOYSA-N 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- JUQXPGLTLBUSIO-UHFFFAOYSA-N N=C=S.COC1=CC=CC=C1 Chemical compound N=C=S.COC1=CC=CC=C1 JUQXPGLTLBUSIO-UHFFFAOYSA-N 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 239000001893 (2R)-2-methylbutanal Substances 0.000 description 1
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 1
- BDPQUWSFKCFOST-UHFFFAOYSA-N 1-isothiocyanato-3-methylbenzene Chemical compound CC1=CC=CC(N=C=S)=C1 BDPQUWSFKCFOST-UHFFFAOYSA-N 0.000 description 1
- KZJRKRQSDZGHEC-UHFFFAOYSA-N 2,2,2-trifluoro-1-phenylethanone Chemical compound FC(F)(F)C(=O)C1=CC=CC=C1 KZJRKRQSDZGHEC-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 150000003930 2-aminopyridines Chemical class 0.000 description 1
- NIXUOGKVYMTEBP-UHFFFAOYSA-N 2-ethylcyclohexane-1-carbaldehyde Chemical compound CCC1CCCCC1C=O NIXUOGKVYMTEBP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- XYRYDVSXZCBWQD-UHFFFAOYSA-N fluorobenzene;isothiocyanic acid Chemical compound N=C=S.FC1=CC=CC=C1 XYRYDVSXZCBWQD-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000005691 oxidative coupling reaction Methods 0.000 description 1
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 1
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
Images
Classifications
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a preparation method of amide, in particular to a method for generating amide by reacting isothiocyanate and aldehyde under the action of oxygen, wherein the reaction temperature can be effectively obtained only when not less than 110 ℃. The process is also suitable for reacting isocyanates with aldehydes to form amides. The preparation method has the advantages of cheap raw materials, wide substrate application, no need of a metal catalyst, an initiator or other activators in the reaction process, greenness and economy, and effective reduction of the cost.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a preparation method of amide.
Background
The amide compound is one of chemical bonds with the strongest functionality accepted in the organic synthesis world, widely exists in a series of natural products, medicines, agricultural chemicals, polymers and functional materials, is a basic component for forming peptide bonds in proteins, and has important significance in pharmaceutical chemistry and material chemistry.
Conventional methods for synthesizing amides are based on coupling of amines to carboxylic acids, or conversion of-OH to a good leaving group (e.g., acid chloride, anhydride) to activate carboxylic acids. However, these processes typically employ stoichiometric amounts of coupling agents and additives, and produce large amounts of toxic chemicals or byproducts. Or a An oxidation process for the synthesis of N-picolinamides from aldehydes and 2-aminopyridines using water as solvent, Sodium Dodecyl Sulfate (SDS) as phase transfer catalyst, based on Cu (OTf)2And iodine; or a method of coupling aldehyde and amine cross-dehydrogenises by nickel catalysis, the success of such oxidative coupling depending on the proper choice of catalyst and organic oxidant by combining [ Ni (cod) ]2]And an organic oxidant (α, α, α -trifluoroacetophenone), to convert aldehydes directly to amides, however, both require the use of metal catalysts, etc.
Therefore, it is of great importance to develop a method for directly synthesizing amides without a coupling agent and a metal catalyst.
Disclosure of Invention
Based on this, there is a need for a process for the preparation of amides. The preparation method does not need a catalyst, an explosive initiator or other activating agents.
A method for preparing amide is characterized by comprising the following steps:
dissolving a compound of a formula (II) and a compound of a formula (III) in an organic solvent, and reacting at a temperature of more than or equal to 110 ℃ in an oxygen atmosphere to prepare a compound amide of a formula (I); or
Dissolving a compound shown in a formula (IV) and a compound shown in a formula (III) in an organic solvent, and reacting at a temperature of more than or equal to 110 ℃ in an oxygen atmosphere to prepare a compound amide shown in a formula (I);
The structures of the compound of formula (I), the compound of formula (II), the compound of formula (III) and the compound of formula (IV) are as follows:
in some of these embodiments, the amide is prepared by a process wherein the reaction temperature is from 110 ℃ to 140 ℃.
In some of the examples, the amide is prepared by a process wherein the reaction temperature is 115 ℃.
In some of these embodiments, the amide is prepared in a process wherein the molar ratio of the compound of formula (ii) to the compound of formula (iii) is 1: (6 to 14), or
The molar ratio of the compound of formula (IV) to the compound of formula (III) is 1: (6-14).
In some of these embodiments, the amide is prepared in a molar ratio of the compound of formula (ii) to the compound of formula (iii) of 1: 10, or
The molar ratio of the compound of formula (IV) to the compound of formula (III) is 1: 10.
in some embodiments, the organic solvent is selected from the group consisting of dichloroethane, dimethylsulfoxide, N, N-dimethylformamide, ethyl acetate, toluene, chlorobenzene, and dichloromethane.
In some of the examples, the amide is prepared in a process wherein the reaction concentration is between 0.1M and 1M.
In some embodiments, the reaction time in the preparation method of the amide is 24-48 h.
In some of the examples, in the process for the preparation of amides, R is characterized1～R5Is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; r6Straight chain alkyl, branched chain alkyl, cycloalkyl and aryl; r7Is hydrogen or halogen.
In some of the embodiments, in the process for preparing an amide, the alkyl group is methyl; the alkoxy is methoxy; the halogen is chlorine or fluorine; the straight-chain alkyl is methyl, ethyl or propyl; the branched alkyl is isopropyl, sec-butyl, tert-butyl, 2-pentyl, 3-pentyl or 3-heptyl; the cycloalkyl is cyclopropyl or cyclohexyl.
Compared with the prior art, the invention has the following beneficial effects:
the inventor obtains a method for generating amide by the reaction of isothiocyanate and aldehyde under the action of oxygen through a large number of experiments, the application range of the substrate is wide, and the effective yield can be obtained only when the reaction temperature is not less than 110 ℃. Further, isocyanate and aldehyde can react to generate amide under the action of oxygen.
The preparation method has the advantages of cheap raw materials, no need of a metal catalyst, an initiator or other activators in the reaction process, greenness, economy, effective cost reduction and good development prospect.
Drawings
FIG. 1 is a photograph of a compound of formula I-1 prepared in example 11An H NMR spectrum;
FIG. 2 shows the preparation of the compound of formula I-1 in example 113C NMR spectrum.
Detailed Description
The process for producing the amide of the present invention will be described in further detail with reference to specific examples. The present invention may be embodied in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
A method for preparing an amide comprising the steps of:
dissolving a compound shown in a formula (I) and a compound shown in a formula (II) in an organic solvent, and reacting at a temperature of more than or equal to 110 ℃ in an oxygen atmosphere to prepare a compound amide shown in a formula (III); and/or
Dissolving a compound shown in a formula (IV) and a compound shown in a formula (II) in an organic solvent, and reacting in an oxygen atmosphere at a temperature of more than or equal to 110 ℃ to prepare a compound amide shown in a formula (III);
the structures of the compounds of formula (I), formula (II), formula (III) and formula (IV) are as follows:
it can be understood that under the action of oxygen, isothiocyanate or isocyanate and aldehyde can produce amide at the temperature of more than or equal to 110 ℃.
In some of the examples, the amide is prepared by a process in which the organic solvent is selected from one of dichloroethane, dimethylsulfoxide, N, N-dimethylformamide, ethyl acetate, toluene, chlorobenzene, and dichloromethane.
In some of the embodiments, the amide is prepared by a method in which the organic solvent is selected from one of dichloroethane, dichloromethane, and ethyl acetate.
Preferably, the organic solvent is selected from dichloroethane.
In some of the examples, the amide preparation method, the reaction temperature is 110 ℃ to 140 ℃.
In some of the examples, the amide preparation method, the reaction temperature is 115 ℃ to 140 ℃.
Preferably, the reaction temperature is 115 ℃.
In some of the examples, the amide is prepared in a process wherein the reaction concentration is between 0.1M and 1M.
In some of the examples, the amide is prepared in a process wherein the reaction concentration is between 0.5M and 1M.
Preferably, the reaction concentration is 0.8M.
In some of these embodiments, the amide is prepared in a molar ratio of the compound of formula (i) to the compound of formula (ii) of 1: (6-14).
In some of these embodiments, the amide is prepared in a molar ratio of the compound of formula (i) to the compound of formula (ii) of 1: (8-14).
Preferably, the molar ratio of the compound of formula (i) to the compound of formula (ii) is 1: 10.
in some embodiments, the reaction time in the preparation method of the amide is 24-48 h.
Preferably, the reaction time is 36 h.
In some of the examples, in the preparation of the amides, R1～R5Is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; r is6Are straight chain alkyl, branched alkyl, cycloalkyl and aryl; r7Is hydrogen or halogenAnd (4) element.
In some of the embodiments, the amide is prepared by a process wherein the alkyl group is methyl; alkoxy is methoxy; halogen is chlorine or fluorine; straight chain alkyl is methyl, ethyl or propyl; the branched alkyl group is isopropyl, sec-butyl, tert-butyl, 2-pentyl, 3-pentyl or 3-heptyl; cycloalkyl is cyclopropyl or cyclohexyl.
Compared with the prior art, the invention has the following beneficial effects:
the invention provides a method for producing amide by reacting isothiocyanate and aldehyde under the action of oxygen, the application of the substrate is wide, and the effective yield can be obtained only when the reaction temperature is not less than 110 ℃. Further, isocyanate and aldehyde can react to generate amide under the action of oxygen.
The preparation method has the advantages of cheap raw materials, no need of a metal catalyst, an initiator or other activators in the reaction process, greenness, economy, effective cost reduction and good development prospect.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
Example 1
In a 10mL sealed tube, isothiocyanate (0.2mmol), aldehyde (2mmol), dichloroethane (0.25mL,0.8M), O were added in this order2And reacting at 115 ℃ for 36 h. TLC monitoring until the isothiocyanate reaction is complete, and stopping the reaction. Extraction with ethyl acetate and water, drying of the organic phase with anhydrous sodium sulfate and spin-drying, and purification of the collected crude product by column chromatography [ eluent petroleum ether: ethyl acetate 10:1(v/v)]Purifying and collecting the product I-1 with the yield of 86%.
White solid, mp127-128 ℃.1H NMR(400MHz,CDCl3)δ7.55(d,J＝7.7Hz, 2H),7.38(s,1H),7.31(t,J＝7.9Hz,2H),7.10(t,J＝7.4Hz,1H),2.08–2.01(m, 1H),1.77–1.66(m,2H),1.61–1.50(m,2H),0.95(t,J＝7.4Hz,6H).13C NMR(100 MHz,CDCl3)δ174.4,138.0,129.0,124.2,120.0,52.4,25.9,12.1.HRMS(ESI): Calcd for C12H18NO[M+H]+:192.13829；Found:192.13796.
Yield ═ molar amount of compound of formula (I-1)/molar amount of phenylisothiocyanate × 100%
Example 2
Essentially the same as in example 1, the volume of only dichloromethane added was different, i.e. the concentration was different.
Phenyl isothiocyanate (0.2mmol), 2-ethylbutyraldehyde (2mmol) and dichloroethane (different in concentration) in different volumes (0.1, 0.3, 0.5, 0.8 and 1.0M) were sequentially added to a 10mL pressure-resistant tube, and O was added to the tube2And reacting at 115 ℃ for 36 h. TLC monitoring until the isothiocyanate reaction is complete, and stopping the reaction. Extraction with ethyl acetate and water, drying of the organic phase with anhydrous sodium sulfate and spin-drying, and purification of the collected crude product by column chromatography [ eluent petroleum ether: ethyl acetate 10:1(v/v)]Purification, isolation of the coupled product I-1, and calculation of the isolated yields are shown in Table 1.
TABLE 1 Effect of different concentrations on the coupling reaction
Example 3
Effect of reaction temperature on the coupling reaction of the invention
The reaction conditions were the same as in example 1 except that the solvents were different (dichloroethane, 1, 4-dioxane, N, N-dimethylformamide, water, ethyl acetate, methanol, toluene, chlorobenzene, acetonitrile, dichloromethane), and the influence of the solvents on the coupling reaction yield was examined, and the isolation yield of product I-1 was determined as shown in Table 2.
TABLE 2 Effect of different reaction solvents on the coupling reaction
Example 4
Effect of the ratio of phenyl isothiocyanate to 2-ethylbutanal on the coupling reaction of the present invention
The reaction conditions were the same as in example 1 except that the molar ratio of phenyl isothiocyanate to 2-ethylbutylaldehyde was different (1:6,1:8,1:10,1:12,1:14), and the influence of the molar ratio of phenyl isothiocyanate to 2-ethylbutylaldehyde on the coupling reaction yield was examined, and the isolation yield of product I-1 was determined as shown in Table 3.
TABLE 3 influence of the molar ratio of phenylisothiocyanate to 2-ethylbutylaldehyde on the coupling reaction
Example 5
Effect of reaction temperature on the coupling reaction of the present invention
The reaction conditions were the same as in example 1 except that the reaction temperatures were different (80 ℃, 100 ℃, 110 ℃, 115 ℃, 120 ℃, 140 ℃), the influence of the reaction temperature on the coupling reaction yield was examined, and the isolation yield measurement results of the product I-1 are shown in Table 4.
TABLE 4 Effect of different temperatures on the dehydrocoupling reaction
Example 6
Synthesis of I-2 Compound of formula
P-toluene isothiocyanate (0.2mmol), 2-ethylbutyraldehyde (2mmol) and dichloroethane (0.8M) were sequentially added to a 10mL pressure-resistant tube, O2And reacting at 115 ℃ for 36 h. TLC monitoring until the isothiocyanate reaction is complete, and stopping the reaction. Extraction with ethyl acetate and water, drying of the organic phase with anhydrous sodium sulfate and spin-drying, and purification of the collected crude product by column chromatography [ eluent petroleum ether: ethyl acetate 10:1(v/v) ]And purifying and collecting the product I-2 with the yield of 82%.
White solid, mp107-108 ℃.
1H NMR(400MHz,CDCl3)δ7.42(d,J＝8.4Hz,2H),7.17(s,1H),7.12(d,J＝ 8.3Hz,2H),2.31(s,3H),2.05–1.97(m,1H),1.77–1.66(m,2H),1.60–1.50(m, 2H),0.95(t,J＝7.4Hz,6H).13C NMR(101MHz,CDCl3)δ174.1,135.4,133.8, 129.4,120.0,52.4,25.9,20.8,12.1.Calcd for C13H20NO[M+H]+:256.15394； Found:256.15338.
Example 7
Synthesis of Compound I-3 represented by the formula
The reaction conditions were the same as in example 5 except that p-tolylisothiocyanate was p-methoxybenzene isothiocyanate, and the yield was 83%.
White solid, mp128-129 ℃.
1H NMR(400MHz,CDCl3)δ7.50–7.42(m,2H),7.25(s,1H),6.87–6.83(m, 2H),3.78(s,3H),2.05–1.97(m,1H),1.77–1.65(m,2H),1.60–1.49(m,2H), 0.95(t,J＝7.4Hz,6H).13C NMR(101MHz,CDCl3)δ174.1,156.4,131.1,121.9, 114.1,55.5,52.2,25.9,12.1.Calcd for C13H20NO2[M+H]+:222.14886；Found: 222.14816.
Example 8
Synthesis of Compound I-4 of formula
The reaction conditions were the same as in example 5 except that p-tolylisothiocyanate was p-chlorobenzenethiocyanate, and the yield was 87%.
White solid, mp132-133 ℃.
1H NMR(400MHz,CDCl3)δ7.49(t,J＝5.8Hz,2H),7.32(s,1H),7.27(dd,J ＝9.1,2.6Hz,2H),2.07–2.00(m,1H),1.77–1.65(m,2H),1.61–1.51(m,2H), 0.95(t,J＝7.4Hz,6H).13C NMR(101MHz,CDCl3)δ174.4,136.5,129.2,128.9, 121.2,52.3,25.8,12.1.Calcd for C12H17ClNO[M+H]+:226.09932；Found: 226.09892.
Example 9
Synthesis of Compound I-5 represented by the formula
The reaction conditions were the same as in example 5 except that p-tolylisothiocyanate was p-fluorobenzene isothiocyanate, and the yield was 84%.
White solid, mp104-106 ℃.
1H NMR(400MHz,CDCl3)δ7.50(dd,J＝8.8,4.8Hz,2H),7.34(s,1H),7.00 (t,J＝8.6Hz,2H),2.06–1.99(m,1H),1.77–1.66(m,2H),1.61–1.51(m,2H), 0.95(t,J＝7.4Hz,6H).13C NMR(101MHz,CDCl3)δ174.3,159.3(d,J＝242Hz), 133.9(d,J＝2.7Hz),121.9(d,J＝7.8Hz),115.5(d,J＝22.3Hz),52.2,25.8,12.1. Calcd for C12H17FNO[M+H]+:210.12887；Found:210.12872.
Example 10
Synthesis of Compound I-6 represented by the formula
The reaction conditions were the same as in example 5 except that p-tolylisothiocyanate was p-trifluorobenzene isothiocyanate, and the yield was 72%.
White solid, mp125-126 ℃.
1H NMR(400MHz,CDCl3)δ7.69(d,J＝8.5Hz,2H),7.57(d,J＝8.6Hz,2H), 7.44(s,1H),2.10–2.04(m,1H),1.78–1.67(m,2H),1.63–1.53(m,2H),0.96(t,J ＝7.4Hz,6H).13C NMR(101MHz,CDCl3)δ174.7,140.9,126.2(q,J＝3.8Hz), 124.1(q,J＝269.8Hz),119.5,52.4,25.8,12.0.Calcd for C13H17F3NO[M+H]+: 260.12568；Found:260.12506.
Example 11
Synthesis of Compound I-7 represented by the formula
The reaction conditions were the same as in example 5 except that p-tolylisothiocyanate was m-tolylisothiocyanate, and the yield was 83%.
White solid, mp81-82 ℃.
1H NMR(400MHz,CDCl3)δ7.45(s,1H),7.30(d,J＝8.1Hz,1H),7.24(s, 1H),7.19(t,J＝7.8Hz,1H),6.92(d,J＝7.5Hz,1H),2.33(s,3H),2.05–2.00(m, 1H),1.77–1.66(m,2H),1.61–1.50(m,2H),0.95(t,J＝7.4Hz,6H).13C NMR (101MHz,CDCl3)δ174.3,138.9,137.9,128.8,125.0,120.6,117.0,52.5,25.9,21.5, 12.1.Calcd for C13H20NO[M+H]+:206.15394；Found:206.15349.
Example 12
Synthesis of Compounds of formula I-8
The reaction conditions were the same as in example 5 except that p-tolylisothiocyanate was m-methoxybenzene isothiocyanate, and the yield was 78%.
White solid, mp104-106 ℃.
1H NMR(400MHz,CDCl3)δ7.40(t,J＝2.0Hz,1H),7.24(s,1H),7.20(t,J＝ 8.1Hz,1H),6.97(d,J＝8.0Hz,1H),6.66(dd,J＝8.2,2.2Hz,1H),3.80(s,3H), 2.04–2.00(m,1H),1.78–1.66(m,2H),1.61–1.51(m,2H),0.96(t,J＝7.4Hz, 6H).13C NMR(101MHz,CDCl3)δ174.3,160.2,139.2,129.6,111.81,110.3,105.4, 55.3,52.6,25.9,12.1.Calcd for C13H20NO2[M+H]+:222.14886；Found: 222.14832.
Example 13
Synthesis of Compounds of formula I-9
The reaction conditions were the same as in example 5 except that the p-tolylisothiocyanate was m-chlorobenzenethiocyanate, and the yield was 86%.
White solid, mp101-102 ℃.
1H NMR(400MHz,CDCl3)δ7.69(d,J＝1.7Hz,1H),7.52(s,1H),7.39(d,J ＝8.1Hz,1H),7.22(t,J＝8.1Hz,1H),7.07(d,J＝8.0Hz,1H),2.09–2.02(m,1H), 1.78–1.65(m,2H),1.61–1.50(m,2H),0.94(t,J＝7.4Hz,6H).13C NMR(101 MHz,CDCl3)δ174.7,139.1,134.6,129.9,124.2,120.1,117.9,52.3,25.8,12.1. Calcd for C12H17ClNO[M+H]+:226.09932；Found:226.09882.
Example 14
Synthesis of I-10 Compound of formula
The reaction conditions were the same as in example 5 except that 2-ethylbutyraldehyde was 2-ethylhexanal, and the yield was 83%.
White solid, mp110-111 ℃.
1H NMR(400MHz,CDCl3)δ7.42(d,J＝7.6Hz,2H),7.12(d,J＝7.0Hz,3H), 2.31(s,3H),2.10–2.03(m,2H),1.77–1.66(m,2H),1.58–1.50(m,2H),1.29(d,J ＝20.5Hz,4H),0.95(t,J＝7.2Hz,3H),0.89(d,J＝5.3Hz,3H).13C NMR(101 MHz,CDCl3)δ174.2,135.3,133.8,129.4,120.0,50.8,32.6,29.9,26.2,22.8,20.8, 14.0,12.1.Calcd for C15H24NO[M+H]+:234.18524；Found:234.18459.
Example 15
Synthesis of Compound I-11 represented by the formula
The reaction conditions were the same as in example 5 except that p-tolylisothiocyanate was p-chlorobenzenethiocyanate and 2-ethylbutyraldehyde was 2-ethylhexanal, and the yield was 79%.
White solid, mp122-123 ℃.
1H NMR(400MHz,CDCl3)δ7.50(d,J＝8.8Hz,2H),7.30(s,1H),7.29–7.25 (m,2H),2.12–2.05(m,1H),1.76–1.64(m,2H),1.60–1.45(m,2H),1.35–1.25 (m,4H),0.94(t,J＝7.4Hz,3H),0.88(t,J＝6.7Hz,3H).13C NMR(101MHz, CDCl3)δ174.5,136.5,129.2,128.9,121.2,50.8,32.5,29.9,26.2,22.8,14.0,12.1. Calcd for C14H21ClNO[M+H]+:254.13062；Found:254.12991.
Example 16
Synthesis of I-12 Compounds of formula
The reaction conditions were the same as in example 1 except that 2-ethylbutyraldehyde was 2-ethylhexanal, and the yield was 85%.
White solid, mp89-90 ℃.
1H NMR(400MHz,CDCl3)δ7.55(d,J＝7.7Hz,2H),7.32(t,J＝7.9Hz,2H), 7.19(s,1H),7.10(t,J＝7.4Hz,1H),2.11–2.05(m,1H),1.76–1.63(m,2H),1.59 –1.47(m,2H),1.36–1.26(m,4H),0.96(t,J＝7.4Hz,3H),0.88(t,J＝6.9Hz,3H). 13C NMR(101MHz,CDCl3)δ174.4,137.9,129.0,124.2,119.9,50.9,32.6,29.9, 26.2,22.8,14.0,12.1.Calcd for C14H22NO[M+H]+:220.16959；Found:220.16911.
Example 17
Synthesis of Compounds of formula I-13
The reaction conditions were the same as in example 1 except that 2-ethylbutyraldehyde was 2-methylpentanal, and the yield was 84%.
White solid, mp98-99 ℃.
1H NMR(400MHz,CDCl3)δ7.54(d,J＝7.8Hz,2H),7.33(s,1H),7.31(t,J＝ 7.9Hz,2H),7.09(t,J＝7.4Hz,1H),2.40–2.31(m,1H),1.77–1.69(m,1H),1.48 –1.32(m,3H),1.22(d,J＝6.8Hz,3H),0.92(t,J＝7.2Hz,3H).13C NMR(101 MHz,CDCl3)δ175.1,138.0,128.9,124.2,119.9,42.46,36.61,20.7,17.9,14.1. Calcd for C12H18NO[M+H]+:192.13829；Found:192.13774.
Example 18
Synthesis of Compounds of formula I-14
The reaction conditions were the same as in example 1 except that 2-ethylbutylaldehyde was 2-methylbutyraldehyde, and the yield was 83%.
White solid, mp119-120 ℃.
1H NMR(400MHz,CDCl3)δ7.54(d,J＝7.8Hz,2H),7.33(s,1H),7.31(t,J＝ 7.8Hz,2H),7.09(t,J＝7.4Hz,1H),2.31–2.23(m,1H),1.82–1.71(m,1H),1.57 –1.46(m,1H),1.22(d,J＝6.8Hz,3H),0.96(t,J＝7.4Hz,3H).13C NMR(101 MHz,CDCl3)δ174.9,138.0,129.0,124.2,119.9,44.2,27.4,17.5,11.9.Calcd for C11H16NO[M+H]+:178.12264；Found:178.12228.
Example 19
Synthesis of I-15 Compound of formula
The reaction conditions were the same as in example 1 except that 2-ethylbutylaldehyde was tert-butylaldehyde, and the yield was 76%.
White solid, mp126-127 ℃.
1H NMR(500MHz,CDCl3)δ7.53(d,J＝7.8Hz,2H),7.32(t,J＝7.9Hz,3H), 7.10(t,J＝7.4Hz,1H),1.32(s,6H).13C NMR(101MHz,CDCl3)δ176.5,138.0, 129.0,124.2,120.0,39.6,27.7.Calcd for C11H16NO[M+H]+:178.12264；Found: 178.12228.
Example 20
Synthesis of Compounds of formula I-16
The reaction conditions were the same as in example 1 except that 2-ethylbutylaldehyde was 2-methylpropionaldehyde, and the yield was 78%.
White solid, mp105-107 ℃.
1H NMR(400MHz,CDCl3)δ7.53(d,J＝7.9Hz,2H),7.31(t,J＝7.9Hz,2H), 7.22(s,1H),7.10(t,J＝7.4Hz,1H),2.51(dt,J＝13.7,6.9Hz,1H),1.26(d,J＝6.9 Hz,6H).13C NMR(101MHz,CDCl3)δ175.2,138.0,129.0,124.2,119.8,36.7,19.6. Calcd for C10H14NO[M+H]+:164.10699；Found:164.10660.
Example 21
Synthesis of Compounds of formula I-17
The reaction conditions were the same as in example 1 except that 2-ethylbutylaldehyde was used in the yield of 79%.
A white solid; mp95-96 ℃.
1H NMR(400MHz,CDCl3)δ7.52(d,J＝7.9Hz,2H),7.36(s,1H),7.31(t,J＝ 7.7Hz,2H),7.09(t,J＝7.3Hz,1H),2.33(t,J＝7.4Hz,2H),1.76(dd,J＝14.9,7.4 Hz,2H),1.00(t,J＝7.4Hz,3H).13C NMR(101MHz,CDCl3)δ171.4,138.0,129.0, 124.2,119.9,39.7,19.1,13.8.Calcd for C10H14NO[M+H]+:164.10699；Found: 164.10669.
Example 22
Synthesis of I-18 Compound represented by the formula
The reaction conditions were the same as in example 1 except that 2-ethylbutylaldehyde was propionaldehyde, and the yield was 72%.
White solid, mp98-99 ℃.
1H NMR(400MHz,CDCl3)δ7.64(s,1H),7.52(d,J＝7.9Hz,2H),7.29(t,J＝ 7.9Hz,2H),7.08(t,J＝7.4Hz,1H),2.37(q,J＝7.6Hz,2H),1.22(t,J＝7.6Hz, 3H).13C NMR(101MHz,CDCl3)δ172.4,138.1,128.9,124.2,120.0,30.7,9.7. Calcd for C9H12NO[M+H]+:150.09134；Found:150.09100.
Example 23
Synthesis of Compounds of formula I-19
The reaction conditions were the same as in example 1 except that 2-ethylbutylaldehyde was acetaldehyde, and the yield was 70%.
White solid, mp115-116 ℃.
1H NMR(400MHz,CDCl3)δ7.65(s,1H),7.54(d,J＝7.8Hz,2H),7.34(t,J＝ 7.8Hz,2H),7.14(t,J＝7.4Hz,1H),2.20(s,3H).13C NMR(101MHz,CDCl3)δ
168.6,138.0,129.0,124.3,120.0,24.5.Calcd for C8H10NO[M+H]+:136.07569；Found:136.07553.
Example 24
Synthesis of I-20 Compound represented by the formula
The reaction conditions were the same as in example 1 except that 2-ethylbutyraldehyde was 2-ethylcyclohexanal, and the yield was 87%.
White solid, mp135-136 ℃.
1H NMR(400MHz,CDCl3)δ7.53(d,J＝7.9Hz,2H),7.32–7.26(m,3H), 7.09(t,J＝7.4Hz,1H),2.23(tt,J＝11.6,3.4Hz,1H),1.95(d,J＝13.0Hz,2H), 1.83(d,J＝11.9Hz,2H),1.70(d,J＝5.2Hz,1H),1.59–1.49(m,2H),1.35–1.23 (m,3H).13C NMR(101MHz,CDCl3)δ174.4,138.1,129.0,124.1,119.8,46.6,29.7, 25.7.Calcd for C13H18NO[M+H]+:204.13829；Found:204.13783.
Example 25
Synthesis of I-21 Compounds of formula
The reaction conditions were the same as in example 1 except that 2-ethylbutylaldehyde was cyclopropylaldehyde, and the yield was 72%.
White solid, mp110-111 ℃.
1H NMR(400MHz,CDCl3)δ7.55(s,1H),7.51(d,J＝7.7Hz,2H),7.30(t,J＝ 7.8Hz,2H),7.08(t,J＝7.2Hz,1H),1.54–1.48(m,1H),1.10–1.06(m,2H),0.85– 0.81(m,2H).13C NMR(101MHz,CDCl3)δ171.9,138.1,129.0,124.0,119.7,15.7, 7.9.Calcd for C10H12NO[M+H]+:162.09134；Found:162.09094.
Example 26
Synthesis of I-22 Compound represented by formula
The reaction conditions were the same as in example 1 except that 2-ethylbutylaldehyde was p-tolualdehyde, and the yield was 62%.
1H NMR(400MHz,DMSO)δ10.14(s,1H),7.87(d,J＝8.2Hz,2H),7.78–7.76(m,2H),7.36–7.32m,4H),7.09(t,J＝7.4Hz,1H),2.39(s,3H).13C NMR (101MHz,DMSO)δ165.8,142.0,139.7,132.5,129.4,129.0,128.1,124.0,120.8, 21.5.
Example 27
Synthesis of Compound I-23 of formula
The reaction conditions were the same as in example 1 except that 2-ethylbutylaldehyde was p-methoxybenzaldehyde, and the yield was 58%.
1H NMR(400MHz,DMSO)δ10.07(s,1H),7.95(d,J＝8.8Hz,2H),7.75(d,J ＝7.8Hz,2H),7.33(t,J＝7.8Hz,2H),7.07(dd,J＝12.5,8.1Hz,3H),3.83(s,3H). 13C NMR(101MHz,DMSO)δ162.3,139.8,130.1,129.0,127.4,123.9,120.8, 114.1,55.9.
Example 28
Synthesis of I-24 Compound represented by formula
The reaction conditions were the same as in example 1 except that the isothiocyanate was 3, 4-dichloroisocyanate, and the yield was 69%.
White solid, mp96-97 ℃.
1H NMR(400MHz,CDCl3)δ7.81(s,1H),7.36(s,2H),7.25(s,1H),2.05– 2.00(m,1H),1.75–1.65(m,2H),1.62–1.52(m,2H),0.95(t,J＝7.4Hz,6H).13C NMR(101MHz,CDCl3)δ174.4,137.3,132.8,130.5,127.4,121.6,119.0,52.4,25.8, 12.1.Calcd for C12H16Cl2NO[M+H]+:260.06035；Found:260.05994.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is specific and detailed, but not to be understood as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent should be subject to the appended claims.
Claims (8)
1. A method for preparing amide is characterized by comprising the following steps:
dissolving a compound shown in a formula (II) and a compound shown in a formula (III) in an organic solvent, and reacting at a temperature of more than or equal to 110 ℃ in an oxygen atmosphere to prepare a compound amide shown in a formula (I); or
Dissolving a compound shown in a formula (IV) and a compound shown in a formula (III) in an organic solvent, and reacting at a temperature of more than or equal to 110 ℃ in an oxygen atmosphere to prepare a compound amide shown in a formula (I);
the structures of the compound of formula (I), the compound of formula (II), the compound of formula (III) and the compound of formula (IV) are as follows:
the organic solvent is selected from one of dichloroethane, 1, 4-dioxane, N, N-dimethylformamide, ethyl acetate, toluene, chlorobenzene and dichloromethane, R 1～R5Is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; r is6Straight chain alkyl, branched chain alkyl, cycloalkyl and aryl; r7Is hydrogen or halogen.
2. The process for producing an amide according to claim 1, wherein the reaction temperature is 110 ℃ to 140 ℃.
3. The process for producing an amide according to claim 2, wherein the reaction temperature is 115 ℃.
4. The process for the preparation of amides according to claim 1, wherein the molar ratio of the compound of formula (ii) to the compound of formula (iii) is 1: (6 to 14), or
The molar ratio of the compound of formula (IV) to the compound of formula (III) is 1: (6-14).
5. The process for the preparation of amides according to claim 4, characterized in that the molar ratio of the compound of formula (II) to the compound of formula (III) is 1: 10, or
The molar ratio of the compound of formula (IV) to the compound of formula (III) is 1: 10.
6. the process for producing an amide according to claim 1, wherein the reaction concentration is 0.1 to 1M.
7. The method for producing an amide according to claim 1, wherein the reaction time is 24 to 48 hours.
8. The process for producing an amide according to claim 1, wherein the alkyl group is a methyl group; the alkoxy is methoxy; the halogen is chlorine or fluorine; the straight-chain alkyl is methyl, ethyl or propyl; the branched alkyl is isopropyl, sec-butyl, tert-butyl, 2-pentyl, 3-pentyl or 3-heptyl; the cycloalkyl is cyclopropyl or cyclohexyl.
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| CN103130696A (en) * | 2013-03-21 | 2013-06-05 | 山东大学 | Anthranilamide compound as well as preparation method and application thereof |
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