CN111116421A - Preparation method of amide derivative - Google Patents
Preparation method of amide derivative Download PDFInfo
- Publication number
- CN111116421A CN111116421A CN201911409119.3A CN201911409119A CN111116421A CN 111116421 A CN111116421 A CN 111116421A CN 201911409119 A CN201911409119 A CN 201911409119A CN 111116421 A CN111116421 A CN 111116421A
- Authority
- CN
- China
- Prior art keywords
- formula
- reaction
- compound
- solvent
- reaction solution
- 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.)
- Granted
Links
- 150000001408 amides Chemical class 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 12
- -1 thiol compounds Chemical class 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 6
- VDEUYMSGMPQMIK-UHFFFAOYSA-N benzhydroxamic acid Chemical compound ONC(=O)C1=CC=CC=C1 VDEUYMSGMPQMIK-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000003513 alkali Substances 0.000 claims abstract description 3
- 239000002994 raw material Substances 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 8
- 239000012044 organic layer Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- 238000002386 leaching Methods 0.000 claims description 5
- 239000000047 product Substances 0.000 claims description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Chemical group 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- WLHCBQAPPJAULW-UHFFFAOYSA-N 4-methylbenzenethiol Chemical compound CC1=CC=C(S)C=C1 WLHCBQAPPJAULW-UHFFFAOYSA-N 0.000 claims description 3
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 claims description 3
- 239000012065 filter cake Substances 0.000 claims description 3
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 abstract description 10
- 239000004202 carbamide Substances 0.000 abstract description 10
- 150000003558 thiocarbamic acid derivatives Chemical class 0.000 abstract description 9
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 abstract description 8
- 239000012948 isocyanate Substances 0.000 abstract description 8
- 150000002513 isocyanates Chemical class 0.000 abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 6
- 238000007167 Hofmann rearrangement reaction Methods 0.000 abstract description 4
- 229910052736 halogen Inorganic materials 0.000 abstract description 4
- 150000002367 halogens Chemical class 0.000 abstract description 4
- 150000001540 azides Chemical class 0.000 abstract description 3
- 239000012295 chemical reaction liquid Substances 0.000 abstract description 3
- 230000008707 rearrangement Effects 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 238000011272 standard treatment Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 235000013877 carbamide Nutrition 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- 150000003573 thiols Chemical class 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- OBTWBSRJZRCYQV-UHFFFAOYSA-N sulfuryl difluoride Chemical compound FS(F)(=O)=O OBTWBSRJZRCYQV-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 4
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- NTRVJFMCRHBODE-UHFFFAOYSA-N 1-(4-methoxyphenyl)-3-phenylurea Chemical compound C1=CC(OC)=CC=C1NC(=O)NC1=CC=CC=C1 NTRVJFMCRHBODE-UHFFFAOYSA-N 0.000 description 2
- XXFBRXQVPJVXFB-UHFFFAOYSA-N 1-benzyl-3-phenylurea Chemical compound C=1C=CC=CC=1NC(=O)NCC1=CC=CC=C1 XXFBRXQVPJVXFB-UHFFFAOYSA-N 0.000 description 2
- RLGZENVXTXVWJN-UHFFFAOYSA-N 1-methyl-1,3-diphenylurea Chemical compound C=1C=CC=CC=1N(C)C(=O)NC1=CC=CC=C1 RLGZENVXTXVWJN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 238000006644 Lossen rearrangement reaction Methods 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 239000005935 Sulfuryl fluoride Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- CXQQNBVIWGUDOJ-UHFFFAOYSA-N [O-]C(NNC1=CC=CC=C1)=[S+]CC1=CC=CC=C1 Chemical compound [O-]C(NNC1=CC=CC=C1)=[S+]CC1=CC=CC=C1 CXQQNBVIWGUDOJ-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 238000006713 insertion reaction Methods 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- DEOCPFBVSXMOQA-UHFFFAOYSA-N s-(4-methylphenyl) n-phenylcarbamothioate Chemical compound C1=CC(C)=CC=C1SC(=O)NC1=CC=CC=C1 DEOCPFBVSXMOQA-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C273/18—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas
- C07C273/1809—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas with formation of the N-C(O)-N moiety
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C333/02—Monothiocarbamic acids; Derivatives thereof
- C07C333/08—Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to carbon atoms of six-membered aromatic rings
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 present invention provides a method for producing an amide derivative, the method comprising: taking benzohydroxamic acid and amine or thiol compounds as raw materials, sequentially adding alkali and solvent into SO2F2Reacting for 2-7 h at 25-50 ℃ in the atmosphere, and after the reaction is finished, carrying out post-treatment on the reaction liquid to obtain the asymmetric urea compound or the thiocarbamate compound; the invention uses cheap, easily obtained and environment-friendly SO2F2As an accelerator, the compound efficiently promotes the generation of an isocyanate intermediate to form a C-N, C-S bond. The generation of isocyanate avoids using a large amount of halogen or azide dangerous reagents, so the isocyanate can be used as a green substitute for the standard treatment conditions of the Coriolis rearrangement and the Hofmann rearrangement. The substrate has wide applicability, and corresponding asymmetric urea and thiocarbamate compounds can be obtained with better yield. The operation process is simple and is suitable for large-scale preparation.
Description
(I) technical field
The present invention relates to the utilization of sulfuryl fluoride (SO)2F2) The compound is used as an accelerant to promote the hydroximic acid to generate the Lossen rearrangement and react with amines or thiols to synthesize the amide derivative: asymmetric urea and thiocarbamate compounds.
(II) background of the invention
The asymmetric urea and thiocarbamate compounds in the amide derivatives, particularly the aromatic asymmetric urea and thiocarbamate compounds, have special physical properties and chemical stability, so that the amide derivatives are widely applied to natural products, medicines, agricultural chemicals and catalysts. One of the more conventional methods for the preparation of asymmetric ureas is via the stepwise reaction of phosgene and its derivatives with amines or amines and thiols. However, the use of highly toxic reagents and the low atom utilization limit the large-scale application of such methods. In recent years, a method of synthesizing asymmetric urea by directly carbonylating carbon monoxide or carbon dioxide with amines or thiols in the presence of a transition metal catalyst has been emerging. Wu et al report that under the action of palladium-catalyzed sodium azide for promotion and ligand, amine and iodobenzene are placed in a carbon monoxide and oxygen atmosphere and heated at 60 ℃ for 12 hours to complete the carbonyl insertion reaction, and an asymmetric urea compound [ adv. Synth. Catal.,2018,360,2820 ]. Valente et al reported the reaction of amines and mercaptans with carbon monoxide to form thiocarbamates over the co-action of two palladium catalysts [ Organometallics,2001,20,5,1028.(DOI:10.1021/om000947+) ]. Asymmetric ureas and thiocarbamates can also be obtained by reacting isocyanates formed by the Hofmann rearrangement (Hofmann rearrangement) of amides or acyl azides by the Cholesh rearrangement (Curtius rearrangement) with amines or thiols in the presence of halogens. Mandal et al reported that hydroxamic acid reacted at 0 ℃ for 15 minutes and then continued at room temperature for 6 hours under the acceleration of ethyl 2-cyano-2- (4-nitrobenzenesulfonyloxyimino) acetate (4-NBsOXY) and N, N-Diisopropylethylamine (DIPEA) to produce isocyanates via the Lossenrearangement (Lossenrearangement) and amines or thiols to give the desired product [ adv.Synth.Catal.,2017,359,168 ]. However, the above methods have some disadvantages, such as the need of transition metal, harsh reaction conditions, low conversion rate, and high toxicity of halogen or azide reagent, and the system is not environment-friendly and not suitable for large-scale application.
Sulfuryl fluoride (SO)2F2) Is a cheap and easily-obtained reagent, and is widely applied to preparing various compounds due to the unique chemical property. Sharpless and Dong Jia, etc. reported for the first time the use of SO under mild conditions2F2The reaction with phenol realizes the high-efficiency connection of sulfonyl fluoride and phenolic hydroxyl, and has quantitative reaction and high conversion rate. The method has the advantages of cheap and easily obtained reagents, solvents and organic bases, no need of transition metals [ Angew.chem., int.Ed.,2014,53,9430 and the like]。-OSO2The structure F can not only serve as an effective linking unit, but also as a good leaving group.
Disclosure of the invention
Aiming at the defects in the prior art, the invention provides a novel method for efficiently, environmentally and economically synthesizing asymmetric urea or thiocarbamate compounds, and the method adopts cheap, easily obtained and environmentally-friendly SO2F2As an accelerant, hydroximic acid compounds and amines or thiols are used as substrates to carry out Lossen rearrangement, so that asymmetric urea or thiocarbamate compounds are efficiently synthesized, the reaction time is obviously shortened, and the operation process is simplified.
The technical scheme adopted by the invention is as follows:
the invention provides a preparation method of an amide derivative shown as a formula (III), which comprises the following steps:
taking benzohydroxamic acid shown in formula (I) and a compound shown in formula (II) as raw materials, sequentially adding alkali and a solvent into SO2F2Reacting for 2-7 h at 25-50 ℃ in the atmosphere, and after the reaction is finished, carrying out post-treatment on the reaction solution to obtain a compound shown in a formula (III); the base is one of the following: DIPEA (N, N-diisopropylethylamine), DBU (1, 8-diazabicycloundecen-7-ene), Et3N (triethylamine), DMAP (4-dimethylaminopyridine), Na2CO3(sodium carbonate), K2CO3(potassium carbonate), CH3ONa (sodium methoxide) ort-BuONa (sodium tert-butoxide); the solvent is one of the following: acetonitrile, dichloromethane, ethyl acetate, water, toluene, dimethylformamide, tetrahydrofuran;
in the formula (II), R comprises 4-methoxyphenyl (4-OCH)3-Ph), methylphenyl (Ph-CH)2-), N-methylanilino or 4-methylphenyl (4-CH)3-Ph); x is nitrogen (N) or sulfur (S); r and X in the formula (III) are the same as R and X in the formula (II).
Further, the compound represented by the formula (II) includes p-anisidine, benzylamine, N-methylaniline, p-methylthiophenol or benzylthiol.
Further, the ratio of the amount of the base to the amount of the substance of hydroxamic acid represented by the formula (I) is 1 to 3: 1; the volume usage of the solvent is 1-5ml/mmol based on the amount of the benzohydroxamic acid substance shown in the formula (I).
Further, the reaction temperature is 25-30 ℃, and the reaction time is 2 h.
Further, the post-treatment method of the reaction liquid is one of the following methods: (1) when X is nitrogen (N), filtering the reaction liquid, and leaching a filter cake to be white by using acetonitrile to obtain the product; (2) when X is sulfur (S), after the reaction is completed, a 5% by mass aqueous HCl solution is added to the reaction solution, and the reaction solution is washed, an organic layer is washed with a 5% by mass aqueous NaOH solution, an organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to remove the solvent, thereby obtaining the product.
Compared with the prior art, the invention has the following beneficial effects:
1. the invention uses cheap, easily obtained and environment-friendly SO2F2As an accelerator, the compound efficiently promotes the generation of an isocyanate intermediate to form a C-N, C-S bond.
2. The generation of isocyanate avoids using a large amount of halogen or azide dangerous reagents, so the isocyanate can be used as a green substitute for the standard treatment condition of the Cholesh rearrangement Hofmann rearrangement.
3. The substrate has wide applicability, and corresponding asymmetric urea and thiocarbamate compounds can be obtained with better yield.
4. The operation process is simple and is suitable for large-scale preparation.
(IV) detailed description of the preferred embodiments
The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto:
example 1: preparation of 1- (4-methoxyphenyl) -3-phenylurea
In a 500mL single-neck flask, 19.20g (140mmol) of hydroxamic acid (I) and p-anisidine (II-1, X ═ N, R) were sequentially added2=4-OCH3Ph)17.24g (140mmol), 150mL of water, 45.24g (2.5eq, 350mmol) of DIPEA in SO2F2Stirring for 2h at 25 ℃ in the atmosphere, filtering after the reaction is finished, washing and leaching a filter cake to be white by using 10mL of acetonitrile to obtain 30.87g of 1- (4-methoxyphenyl) -3-phenylurea shown in the formula (III-1) with the yield of 91%.
NMR hydrogen spectrum (500MHz, DMSO-d)6)(δ,ppm):8.57(s,1H),8.46(s,1H),7.44(d,J=7.6Hz,2H),7.39–7.33(m,2H),7.27(t,J=7.9Hz,2H),6.95(t,J=7.3Hz,1H),6.90–6.84(m,2H),3.36(s,3H).
Nuclear magnetic resonance carbon spectrum (126MHz, DMSO-d)6)(δ,ppm):154.93,153.19,140.36,133.17,129.20,122.06,120.49,118.54,114.45,55.64.
Example 2: preparation of 1-benzyl-3-phenylurea
In a 500mL single-neck flask, 19.20g (140mmol) of hydroxamic acid (I) and benzylamine (II-2, X ═ N, R) were sequentially added2=Ph-CH2-)15.00g (140mmol), 150mL of dichloromethane, 63.94g (3.0eq, 420mmol) of DBU in SO2F2Stirring for 1h at 25 ℃ in the atmosphere, filtering after the reaction is finished, and leaching to white with 10mL of acetonitrile to obtain 26.g of (III-2) 1-benzyl-3-phenylurea with the yield of 83%.
NMR hydrogen spectrum (500MHz, DMSO-d)6)(δ,ppm):8.58(s,1H),7.44–7.40(m,2H),7.33(dt,J=10.9,7.1Hz,4H),7.27–7.18(m,3H),6.90(t,J=7.3Hz,1H),6.64(t,J=5.7Hz,1H),4.31(d,J=5.9Hz,2H).
Nuclear magnetic resonance carbon spectrum (126MHz, DMSO-d)6)(δ,ppm):155.24,140.46,128.63,128.29,127.76,127.10,126.70,121.07,117.69,42.73.
Example 3: preparation of 3-phenyl-N-methyl-N-phenylurea
In a 500mL single-neck flask, 19.20g (140mmol) of hydroxamic acid (I) and N-methylaniline (II-3, X ═ N, R) were added in this order215.00g (140mmol) of N-methylanilino), 150mL of acetonitrile, 18.10g (3.0eq, 420mmol) of Na2CO3In SO2F2Stirring for 6 hours at 30 ℃ in the atmosphere, filtering after the reaction is finished, and leaching with 10mL of acetonitrile to white to obtain 25.98g of 3-phenyl-N-methyl-N-phenylurea shown in the formula (III-3) with the yield of 82%.
NMR hydrogen spectrum (500MHz, DMSO-d)6)(δ,ppm):8.12(s,1H),7.46–7.38(m,4H),7.33(dd,J=8.4,1.1Hz,2H),7.27–7.20(m,3H),6.95(t,J=7.3Hz,1H),3.28(s,3H).
Nuclear magnetic resonance carbon spectrum (126MHz, DMSO-d)6)(δ,ppm):154.74,144.09,140.05,129.24,128.26,126.22,125.77,122.04,119.90,37.55.
Example 4: preparation of S- (p-tolyl) phenylthiocarbamate
In a 500mL single-neck flask, 19.20g (140mmol) of hydroxamic acid (I) and p-methylthiophenol (II-4, X ═ S, R ═ 4-CH) were sequentially added3Ph)17.39g (140mmol), 600mL ethyl acetate, 45.24g (1.0eq, 140mmol) of DIPEA in SO2F2Stirring for 7h at 50 deg.C in atmosphere, adding 200mL of 5% HCl aqueous solution, washing, collecting organic layer, and adding200mL of a 5% NaOH aqueous solution was washed, the organic layer was washed with 300mL of saturated brine, and the mixture was dried over anhydrous sodium sulfate (30 g) and concentrated to remove the solvent, whereby 27.25g of S- (p-tolyl) phenylcarbamate represented by the formula (III-4) was obtained in 80% yield.
NMR hydrogen spectrum (500MHz, DMSO-d)6)(δ,ppm):10.47(s,1H),7.50(d,J=8.5Hz,2H),7.41(d,J=8.0Hz,2H),7.33–7.28(m,2H),7.26(d,J=7.9Hz,2H),7.06(t,J=7.4Hz,1H),2.35(s,3H)。
Nuclear magnetic resonance carbon spectrum (126MHz, DMSO-d)6)(δ,ppm):163.10,138.84,135.29,129.67,128.88,124.52,123.52,119.05,113.93,20.79.
Example 5: preparation of S-benzylphenylaminothiocarbamate
In a 500mL single-neck flask, 19.20g (140mmol) of hydroxamic acid (I) and benzyl mercaptan (II-5, X ═ S, R) were added in this order2=Ph-CH2-)17.39g (140mmol), 300mL toluene, 15.13g (2.0eq, 280mmol) CH3ONa in SO2F2Stirring for 4 hours at 40 ℃ in the atmosphere, after the reaction is finished, adding 200mL of 5% HCl aqueous solution with mass concentration into the reaction solution for washing, taking the organic layer for washing with 200mL of 5% NaOH aqueous solution with mass concentration, taking the organic layer for washing with 300mL of saturated saline solution, drying 30g of anhydrous sodium sulfate, and concentrating to remove the solvent to obtain 26.23g of 1, 3-S-benzyl phenyl carbamate with the yield of 77%.
NMR hydrogen spectrum (500MHz, DMSO-d)6)(δ,ppm):10.35(s,1H),7.53(d,J=7.6Hz,2H),7.37(d,J=7.4Hz,2H),7.35–7.29(m,4H),7.25(t,J=7.2Hz,1H),7.06(t,J=7.4Hz,1H),4.17(s,2H)。
Nuclear magnetic resonance carbon spectrum (126MHz, DMSO-d)6)(δ,ppm):164.33,138.86,138.72,128.87,128.70,128.43,126.96,123.42,119.02,32.91.
Claims (7)
1. A process for producing an amide derivative represented by the formula (III), which comprises:
taking benzohydroxamic acid shown in formula (I) and a compound shown in formula (II) as raw materials, sequentially adding alkali and a solvent into SO2F2Reacting for 2-7 h at 25-50 ℃ in the atmosphere, and after the reaction is finished, carrying out post-treatment on the reaction solution to obtain a compound shown in a formula (III); the base is one of the following: n, N-diisopropylethylamine, 1, 8-diazabicycloundecen-7-ene, triethylamine, 4-dimethylaminopyridine, sodium carbonate, potassium carbonate, sodium methoxide or sodium tert-butoxide; the solvent is one of the following: acetonitrile, dichloromethane, ethyl acetate, water, toluene, dimethylformamide or tetrahydrofuran;
in the formula (II), R comprises 4-methoxyphenyl, methylphenyl, N-methylanilino or 4-methylphenyl; x is nitrogen or sulfur; r, X in formula (III) is the same as R, X in formula (II).
2. The method according to claim 1, wherein the compound of formula (II) is p-anisidine, benzylamine, N-methylaniline, p-methylthiophenol, or benzylthiol.
3. The method according to claim 1, wherein the ratio of the amount of base to the amount of hydroxamic acid compound of formula (I) is 1 to 3: 1.
4. the process according to claim 1, wherein the solvent is used in a volume of 1 to 5ml/mmol based on the amount of the hydroxamic acid compound of formula (I).
5. The process according to claim 1, wherein the reaction temperature is 25 to 30 ℃ and the reaction time is 2 hours.
6. The method according to claim 1, wherein when X ═ nitrogen, the reaction solution post-treatment method is: and filtering the reaction solution, and leaching a filter cake to be white by using acetonitrile to obtain the product.
7. The method according to claim 1, wherein when X ═ sulfur, the reaction solution is worked up by: after the reaction is finished, adding an HCl aqueous solution with the mass concentration of 5% into the reaction solution for washing, taking the organic layer, then washing with an NaOH aqueous solution with the mass concentration of 5%, taking the organic layer, washing with saturated saline solution, drying with anhydrous sodium sulfate, and concentrating to remove the solvent to obtain the product.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911409119.3A CN111116421B (en) | 2019-12-31 | 2019-12-31 | Preparation method of amide derivative |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911409119.3A CN111116421B (en) | 2019-12-31 | 2019-12-31 | Preparation method of amide derivative |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111116421A true CN111116421A (en) | 2020-05-08 |
CN111116421B CN111116421B (en) | 2022-01-25 |
Family
ID=70506572
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911409119.3A Active CN111116421B (en) | 2019-12-31 | 2019-12-31 | Preparation method of amide derivative |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111116421B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114213286A (en) * | 2021-12-13 | 2022-03-22 | 湖北文理学院 | Synthetic method of urea derivative |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0789924A (en) * | 1993-09-21 | 1995-04-04 | Shiratori Seiyaku Kk | Production of carbamate compounds |
CN104710259A (en) * | 2015-03-16 | 2015-06-17 | 浙江工业大学 | Synthesizing method for amide compound |
CN106242989A (en) * | 2015-06-15 | 2016-12-21 | 浙江工业大学 | A kind of synthetic method of oxanilide analog derivative |
US20170158598A1 (en) * | 2012-12-19 | 2017-06-08 | Dow Agrosciences Llc | Pesticidal compositions and processes related thereto |
CN108290832A (en) * | 2015-09-04 | 2018-07-17 | 美国陶氏益农公司 | There are molecule and relative intermediate, the composition and method of desinsection effectiveness |
-
2019
- 2019-12-31 CN CN201911409119.3A patent/CN111116421B/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0789924A (en) * | 1993-09-21 | 1995-04-04 | Shiratori Seiyaku Kk | Production of carbamate compounds |
US20170158598A1 (en) * | 2012-12-19 | 2017-06-08 | Dow Agrosciences Llc | Pesticidal compositions and processes related thereto |
CN104710259A (en) * | 2015-03-16 | 2015-06-17 | 浙江工业大学 | Synthesizing method for amide compound |
CN106242989A (en) * | 2015-06-15 | 2016-12-21 | 浙江工业大学 | A kind of synthetic method of oxanilide analog derivative |
CN108290832A (en) * | 2015-09-04 | 2018-07-17 | 美国陶氏益农公司 | There are molecule and relative intermediate, the composition and method of desinsection effectiveness |
Non-Patent Citations (6)
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114213286A (en) * | 2021-12-13 | 2022-03-22 | 湖北文理学院 | Synthetic method of urea derivative |
CN114213286B (en) * | 2021-12-13 | 2022-12-30 | 湖北文理学院 | Synthetic method of urea derivative |
Also Published As
Publication number | Publication date |
---|---|
CN111116421B (en) | 2022-01-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110683969B (en) | Urea derivative and synthetic method thereof | |
CN101863858A (en) | Synthetic method of bentazone | |
CN111116421B (en) | Preparation method of amide derivative | |
CN113735751B (en) | Method for preparing aryl isothiourea | |
JP5681985B2 (en) | Production method of urea compounds by carbon dioxide fixation | |
CN111116420B (en) | Preparation method of symmetrical urea compound | |
CN110156721B (en) | Using diazo esters, cyclic ethers, amines and CO 2 Method for synthesizing carbamate | |
EP2821389A1 (en) | Production method for compound comprising amino group and/or hydroxyl group | |
CN101671299A (en) | Method for synthesizing Nexavar | |
CN1039804A (en) | The preparation method of aryl sulfuryl isocyanate and derivative thereof | |
JP2021191734A (en) | Method for producing urea derivative | |
CN109761882A (en) | The synthetic method of Carprofen and its intermediate | |
CN109734650A (en) | The synthetic method of Carprofen and its intermediate | |
CN115340471B (en) | One-pot preparation process of cyanamide compound | |
CN113912526B (en) | Preparation method of N-acetyl tellurium carbamic acid ester compound | |
CN118496177B (en) | Method for preparing kali lazine and intermediate thereof | |
CN116462611B (en) | Method for preparing polyarylguanidine by using diaryl hypervalent iodine reagent | |
CN116396196B (en) | Method for preparing amido isothiocyanate/amido thiourea compound in one pot | |
CN115536557B (en) | Photoacid generator intermediate and preparation method of photoacid generator | |
CN114163395B (en) | Chiral oxazolinone derivative, synthesis method and application thereof in preparation of linezolid and rivaroxaban | |
CN115368258A (en) | Preparation process of amide compound | |
CN110590641B (en) | Green preparation method of 3-hydroxyisoindole-1-ketone series compounds | |
CN115784937A (en) | Preparation method of N-aromatic ureide compound | |
EP2305634A1 (en) | The new preparation of aliphatic amines with sulphonyl group and their salts | |
CN113979885A (en) | Method for synthesizing amide compound |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right |
Effective date of registration: 20240912 Address after: No. 9777, hongshiwu Road, Xiaoshan Linjiang Industrial Park, Xiaoshan District, Hangzhou, Zhejiang 311200 Patentee after: HANGZHOU YINGTAI BIOTECHNOLOGY Co.,Ltd. Country or region after: China Address before: 310014 No. 18 Chao Wang Road, Xiacheng District, Zhejiang, Hangzhou Patentee before: JIANG University OF TECHNOLOGY Country or region before: China |