CN111116421B - Preparation method of amide derivative - Google Patents
Preparation method of amide derivative Download PDFInfo
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- CN111116421B CN111116421B CN201911409119.3A CN201911409119A CN111116421B CN 111116421 B CN111116421 B CN 111116421B CN 201911409119 A CN201911409119 A CN 201911409119A CN 111116421 B CN111116421 B CN 111116421B
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- 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
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- 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
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 processing conditions of the Kitius rearrangement and the Hofmann rearrangement. The substrate has wide applicability, and corresponding asymmetric urea and thiocarbamate can be obtained with better yieldA compound is provided. 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 Lossen rearrangement (Lossen rearrangement) 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) or t-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,after the reaction is finished, filtering is carried out, and 10mL of acetonitrile is used for leaching to be white, so that 26.g of (III-2) 1-benzyl-3-phenylurea can be obtained, and the yield is 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 ═ are sequentially added4-CH3Ph)17.39g (140mmol), 600mL ethyl acetate, 45.24g (1.0eq, 140mmol) of DIPEA in SO2F2Stirring the mixture at 50 ℃ for 7 hours in an atmosphere, after the reaction is finished, adding 200mL of 5% HCl aqueous solution by mass concentration into the reaction solution, washing the organic layer with 200mL of 5% NaOH aqueous solution by mass concentration, washing the organic layer with 300mL of saturated saline solution, drying 30g of anhydrous sodium sulfate, and concentrating to remove the solvent to obtain 27.25g of S- (p-tolyl) phenylcarbamate shown in formula (III-4) with the yield of 80%.
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, D)MSO-d6)(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 is 4-methoxyphenyl, benzyl or 4-methylphenyl; x is NH or S; r, X in formula (III) is the same as R, X in formula (II);
or of the formula (II)
Then the formula (III) is
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 ═ NH, 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 ═ S, the reaction solution post-treatment method is: 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.
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| CN104710259A (en) * | 2015-03-16 | 2015-06-17 | 浙江工业大学 | Synthesizing method for amide compound |
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| DK2934135T3 (en) * | 2012-12-19 | 2018-04-23 | Dow Agrosciences Llc | PESTICIDE COMPOSITIONS AND PROCEDURES RELATED TO IT |
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| 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 |
| 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 |
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| Ethyl 2-(tert-Butoxycarbonyloxyimino)-2-cyanoacetate (Boc-Oxyma): An Efficient Reagent for the Racemization Free Synthesis of Ureas, Carbamates and Thiocarbamates via Lossen Rearrangement;Bhubaneswar Mandal et al;《Adv. Synth. Catal.》;20161209;第359卷;168-176 * |
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