CN113861108B - Method for synthesizing carbamate compound by esterification reaction of amide and alcohol at room temperature - Google Patents
Method for synthesizing carbamate compound by esterification reaction of amide and alcohol at room temperature Download PDFInfo
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- CN113861108B CN113861108B CN202111253779.4A CN202111253779A CN113861108B CN 113861108 B CN113861108 B CN 113861108B CN 202111253779 A CN202111253779 A CN 202111253779A CN 113861108 B CN113861108 B CN 113861108B
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- -1 carbamate compound Chemical class 0.000 title claims abstract description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 150000001408 amides Chemical class 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 title claims abstract description 22
- 238000005886 esterification reaction Methods 0.000 title claims abstract description 15
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 239000011259 mixed solution Substances 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 8
- 150000003624 transition metals Chemical class 0.000 claims abstract description 8
- 238000004440 column chromatography Methods 0.000 claims abstract description 6
- 239000000706 filtrate Substances 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 239000007800 oxidant agent Substances 0.000 claims abstract description 4
- 230000001590 oxidative effect Effects 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 238000003756 stirring Methods 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical group Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical compound [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 claims description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 abstract description 9
- 239000000758 substrate Substances 0.000 abstract description 9
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 231100000252 nontoxic Toxicity 0.000 abstract description 2
- 230000003000 nontoxic effect Effects 0.000 abstract description 2
- 239000000376 reactant Substances 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- OOCCDEMITAIZTP-QPJJXVBHSA-N (E)-cinnamyl alcohol Chemical compound OC\C=C\C1=CC=CC=C1 OOCCDEMITAIZTP-QPJJXVBHSA-N 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical class [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- UPBDTNXNZHJUMB-UHFFFAOYSA-N n-(3-methylpyridin-2-yl)-2,2-diphenylacetamide Chemical compound CC1=CC=CN=C1NC(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 UPBDTNXNZHJUMB-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 239000013132 MOF-5 Substances 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- OOCCDEMITAIZTP-UHFFFAOYSA-N allylic benzylic alcohol Natural products OCC=CC1=CC=CC=C1 OOCCDEMITAIZTP-UHFFFAOYSA-N 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 238000007248 oxidative elimination reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- KFHRHCHIPAPKLI-UHFFFAOYSA-N 2,2-diphenyl-n-pyridin-2-ylacetamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)C(=O)NC1=CC=CC=N1 KFHRHCHIPAPKLI-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 229940076286 cupric acetate Drugs 0.000 description 1
- 229960004643 cupric oxide Drugs 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- USFPINLPPFWTJW-UHFFFAOYSA-N tetraphenylphosphonium Chemical compound C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 USFPINLPPFWTJW-UHFFFAOYSA-N 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000004454 trace mineral analysis Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a method for synthesizing carbamate compounds by utilizing esterification reaction of amide and alcohol at room temperature, which comprises the following steps of dissolving amide, a transition metal catalyst and alcohol in an organic solvent, and stirring for 1-6 hours at room temperature to obtain a mixed solution; filtering the mixed solution, concentrating the filtrate, and performing column chromatography to obtain the carbamate compound. The method directly uses common non-toxic amide as a substrate, and the substrate range is wide. The reaction uses oxygen in air as an oxidant, the reactants do not need to be excessive, the utilization rate of raw materials is high, the range of substrates is wide, the reaction condition is mild, the operation is simple, the time is short, the yield is high, and the method is suitable for being applied to industrial production.
Description
Technical Field
The invention relates to a method for synthesizing a carbamate compound, in particular to a method for synthesizing a carbamate compound by utilizing esterification reaction of amide and alcohol, belonging to the technical field of preparation of carbamate compounds.
Background
The carbamate compound is widely used as an important compound in chemical fertilizers, pesticides, medicines and fine chemical products. The traditional method for synthesizing the carbamate compound is synthesized by utilizing nucleophilic addition reaction of isocyanate and alcohol. However, the requirement for sustainable development is not met due to the highly toxic nature of the isocyanate, the environmental unfriendly nature and the limited substrate. In recent years, chemists have increasingly tended to synthesize carbamate compounds using transition metal catalyzed processes under mild conditions to increase synthesis yields and substrate versatility. However, these known reactions tend to be substrate toxic, have limited substrate range, and require high temperatures and other harsh conditions that are not widely applicable to industrial processes. At room temperature, the reaction of directly preparing the carbamate compound by using the amide and the alcohol without toxicity is not reported so far.
Disclosure of Invention
The invention provides a method for synthesizing carbamate compounds by utilizing esterification reaction of amide and alcohol at room temperature, which can be used for efficiently preparing various carbamate compounds.
The method mainly uses various copper salts, copper oxides, supported nano copper catalysts and homogeneous/heterogeneous palladium catalysts as catalysts, oxygen in air is used as an oxidant, and various carbamate derivatives are prepared through C-C bond oxidative cleavage of amide and addition reaction of alcohol at room temperature, wherein the reaction adopts a combined strategy of chelate assistance and C-C bond oxidative cleavage, and the technical barrier that the amide cannot directly react with the alcohol to prepare the carbamate compounds through C-C bond cleavage at room temperature is broken.
The chemical reaction equation involved in the method of the invention is as follows:
the method for synthesizing the carbamate compound by utilizing the esterification reaction of the amide and the alcohol comprises the following steps:
(1) Dissolving amide, a transition metal catalyst and alcohol in an organic solvent to obtain a mixed solution A; preferably, the molar ratio of the amide, the transition metal catalyst and the alcohol is 1:0.02 to 0.5:1-4.
The amide isWherein R is-> (n＝1,2,3,4,5,6)；(n＝1,2,3,4,5,6)；/>(X＝-CN,-NO 2 ,-F,-Cl,-Br,-I,-OH,-OCH 3 ,-OC 2 H 5 ,-SH,-NH 2 ,-SO 3 H,-COOH,-COOCH 3 ,-COOC 2 H 5 ,-CONH 2 ,-CONHCH 3 ,-COCH 3 ,-COC 2 H 5 -CHO); wherein hetAr is->
The transition metal catalyst is copper chloride, copper sulfate, cuprous bromide, cupric acetate, cuprous iodide, cuprous cyanide, cupric oxide, cuprous oxide, and supported nano copper catalyst (Cu/Al) 2 O 3 Cu/C, cu/MOF-5) or palladium acetate, palladium trifluoroacetate, palladium chloride, tetraphenylphosphine palladium, supported nano-palladium catalyst (Pd/Al) 2 O 3 ，Pd/C,Pd/MOF-5)；
The alcohol is R 1 OH, wherein R is 1 Is that(n＝0,1,2,3,4,5,6)，/>(n＝0,1,2,3,4,5,6)，(n＝0,1,2,3,4,5,6)，/>(n＝0,1,2,3,4,5,6)，/>
The organic solvent is acetonitrile, dichloromethane, dichloroethane, tetrahydrofuran, toluene, chlorobenzene, chloroform, N-dimethylformamide, dimethyl sulfoxide;
(2) Stirring the mixed solution A for 1-6 hours at room temperature to obtain mixed solution B;
the reaction in the step (2) is not limited in terms of reaction time, and the reaction may be carried out by taking samples at regular time and performing trace analysis by conventional means such as Thin Layer Chromatography (TLC), and the end point of the reaction may be regarded as the end point of the reaction when one or more of the raw materials are reacted.
(3) Filtering the mixed solution B, concentrating the filtrate, and performing column chromatography to obtain various carbamate compounds.
Compared with the prior art, the invention has the following beneficial effects:
according to the method, the carbamate compound is synthesized through the esterification reaction of the amide and the alcohol, and the reactants are not required to be excessive. Compared with the prior art, the method directly uses common non-toxic amide as a substrate without using extremely toxic or toxic substances such as isocyanate and the like as a reaction substrate. At room temperature, oxygen in the air is used as an oxidant, and the method realizes the chemical specificity C-C bond rupture of the amide and further performs esterification reaction with alcohol to obtain various carbamate compounds. The method has the advantages of mild reaction conditions, simple operation, short time and high yield, and is suitable for being applied to industrial production.
Detailed Description
Example 1
This example prepares ethyl (3-methylpyridin-2-yl) carbamate by esterification of N- (3-methylpyridin-2-yl) -2-naphthamide with ethanol.
0.1mmol of N- (3-methylpyridin-2-yl) -2-naphthamide, 0.01mmol of copper chloride and 0.2mmol of ethanol are dissolved in 1mL of dichloromethane, and the obtained reaction mixture is stirred at room temperature for 6 hours; the obtained mixed solution was filtered, the filtrate was concentrated, and column chromatography was performed to obtain ethyl (3-methylpyridin-2-yl) carbamate in a yield of about 73%.
The nuclear magnetic monitoring data are as follows: 1 HNMR(600MHz,CDCl 3 )δ8.27(d,J＝4.2Hz,1H),7.54(d,J＝7.4Hz,2H),7.06(dd,J＝7.4,4.9Hz,1H),4.22(q,J＝7.1Hz,2H),2.30(s,3H),1.31(t,J＝7.1Hz,3H)； 13 CNMR(151MHz,CDCl 3 )δ153.9,149.6,145.8,139.9,127.1,121.0,61.5,18.0,14.5.
example 2
This example prepares methyl (3-methylpyridin-2-yl) carbamate by esterification of N- (3-methylpyridin-2-yl) -2, 2-diphenylacetamide with methanol.
0.5 mmole of N- (3-methylpyridin-2-yl) -2, 2-diphenylacetamide, 0.05 mmole of palladium acetate, 1 mmole of methanol were dissolved in 2mL of acetonitrile, and the resulting reaction mixture was stirred for 6 hours; the obtained mixed solution was filtered, the filtrate was concentrated, and column chromatography was performed to obtain methyl (3-methylpyridin-2-yl) carbamate in a yield of about 59%.
The nuclear magnetic monitoring data are as follows: 1 HNMR(600MHz,CDCl 3 )δ8.26(d,J＝4.1Hz,1H),7.54(d,J＝7.5Hz,1H),7.37(s,1H),7.07(dd,J＝7.4,4.9Hz,1H),3.78(s,3H),2.30(s,3H)； 13 C NMR(151MHz,CDCl 3 )δ154.3,149.4,145.8,139.9,127.0,121.1,52.6,17.9.
example 3
This example prepares cinnamyl (3-methylpyridin-2-yl) carbamate by esterification of N- (3-methylpyridin-2-yl) -2, 2-diphenylacetamide with cinnamyl alcohol.
0.1 mmole of N- (pyridin-2-yl) -2, 2-diphenylacetamide, 0.005 mmole of copper acetate, 0.1 mmole of cinnamyl alcohol were dissolved in 1mL of dichloroethane, and the resulting reaction mixture was stirred at room temperature for 2 hours; filtering the obtained mixed solution, concentrating the filtrate, and performing column chromatography to obtain cinnamyl (3-methylpyridin-2-yl) carbamate with the yield of about 87%.
The nuclear magnetic monitoring data are as follows: 1 H NMR(600MHz,CDCl 3 )δ8.28(s,1H),7.53(d,J＝7.5Hz,2H),7.39(d,J＝7.4Hz,2H),7.32(t,J＝7.6Hz,2H),7.26(t,J＝7.3Hz,1H),7.06(dd,J＝7.3,4.9Hz,1H),6.68(d,J＝15.9Hz,1H),6.36-6.29(m,1H),4.83(d,J＝6.4Hz,2H),2.30(s,3H)； 13 C NMR(151MHz,CDCl 3 )δ153.6,149.4,145.9,139.9,136.3,134.20,128.6,128.1,127.0,126.7,123.4,121.1,66.0,18.0.
examples 4 to 13
In examples 4 to 13, the reaction conditions and the material ratios of example 3 were used, and only the types of the amide and the alcohol were changed, and the raw materials used in each example and the obtained products and the product yields were shown in Table 1.
TABLE 1
The nuclear magnetic resonance monitoring data of the target products in examples 4 to 13 are as follows:
example 4: n-hexyl (3-methylpyridin-2-yl) carbamate
1 H NMR(600MHz,CDCl 3 )δ8.27(d,J＝4.2Hz,1H),7.54(d,J＝7.4Hz,2H),7.06(dd,J＝7.4,4.9Hz,1H),4.16(t,J＝6.8Hz,2H),2.30(s,3H),1.69-1.61(m,2H),1.41-1.34(m,2H),1.33-1.27(m,4H),0.89(t,J＝6.8Hz,3H)； 13 C NMR(151MHz,CDCl 3 )δ154.0,149.6,145.8,139.8,127.1,121.0,65.7,31.5,28.9,25.5,22.6,18.0,14.0.
Example 5: benzyl (3-methylpyridin-2-yl) carbamate
1 H NMR(600MHz,CDCl 3 )δ8.23(d,J＝3.4Hz,1H),7.65(s,1H),7.52(d,J＝7.5Hz,1H),7.41-7.31(m,5H),7.03(dd,J＝7.4,4.7Hz,1H),5.20(s,2H),2.28(s,3H)； 13 C NMR(151MHz,CDCl 3 )δ153.6,149.4,145.9,139.9,136.1,128.6,128.3,128.3,127.0,121.1,67.3,18.0.
Example 6: pyridin-2-methyl (3-methylpyridin-2-yl) carbamic acid ester
1 H NMR(600MHz,CDCl 3 )δ8.60(d,J＝4.6Hz,1H),8.27(d,J＝4.1Hz,1H),7.70(t,J＝6.9Hz,1H),7.54(d,J＝7.4Hz,1H),7.41(d,J＝7.8Hz,1H),7.24(dd,J＝7.3,5.0Hz,1H),7.06(dd,J＝7.5,4.9Hz,1H),5.33(s,2H),2.31(s,3H)； 13 C NMR(151MHz,CDCl 3 )δ156.0,153.4,149.4,149.3,145.9,139.8,136.8,126.9,122.9,121.9,121.2,67.7,17.9
Example 7: isobutyl (3-methylpyridin-2-yl) carbamate
1 H NMR(600MHz,CDCl 3 )δ8.27(d,J＝4.2Hz,1H),7.54(d,J＝7.4Hz,1H),7.36(s,1H),7.06(dd,J＝7.4,4.9Hz,1H),4.88-4.80(m,1H),2.30(s,3H),1.70-1.62(m,1H),1.61-1.53(m,1H),1.27(d,J＝6.3Hz,3H),0.93(t,J＝7.5Hz,3H)； 13 C NMR(151MHz,CDCl3)δ153.6,149.6,145.8,139.8,127.0,121.0,73.6,29.0,20.0,18.0,9.7.
Example 8: cyclohexyl (3-methylpyridin-2-yl) carbamate
1 H NMR(600MHz,CDCl 3 )δ8.27(d,J＝4.2Hz,1H),7.54(d,J＝7.4Hz,1H),7.48(s,J＝65.9Hz,1H),7.06(dd,J＝7.5,4.9Hz,1H),4.78-4.69(m,1H),2.30(s,3H),1.97-1.91(m,2H),1.76-1.70(m,2H),1.58-1.52(m,1H),1.49-1.42(m,2H),1.41-1.34(m,2H),1.29-1.22(m,1H)； 13 CNMR(151MHz,CDCl 3 )δ153.4,149.7,145.7,139.9,127.2,121.0,74.0,31.9,25.4,23.8,18.0.
Example 9: bis (4-chlorophenyl) methyl (3-methylpyridin-2-yl) carbamate
1 H NMR(600MHz,CDCl 3 )δ8.24(d,J＝3.3Hz,1H),7.94(s,1H),7.55(d,J＝6.9Hz,1H),7.29(d,J＝8.5Hz,4H),7.24(d,J＝8.5Hz,4H),7.07(dd,J＝7.3,4.9Hz,1H),6.80(s,1H),2.26(s,3H)； 13 C NMR(151MHz,CDCl 3 )δ152.6,149.2,145.8,140.0,138.3,134.0,128.8,128.7,128.5,127.9,127.3,121.4,76.7,17.9.
Example 10: nerol- (3-methylpyridin-2-yl) carbamate
1 H NMR(600MHz,CDCl 3 )δ8.26(d,J＝4.1Hz,1H),7.54(d,J＝7.4Hz,1H),7.06(dd,J＝7.3,4.9Hz,1H),5.41(t,J＝7.1Hz,1H),5.10(t,J＝6.8Hz,1H),4.66(d,J＝7.2Hz,2H),2.29(s,3H),2.17–2.11(m,2H),2.11–2.05(m,2H),1.78(s,3H),1.68(s,3H),1.60(s,3H)； 13 C NMR(151MHz,CDCl 3 )δ153.7,149.5,145.8,142.7,139.8,132.2,126.8,123.6,121.0,119.3,62.1,32.2,26.7,25.7,23.5,18.0,17.7
Example 11: borneol- (3-methylpyridin-2-yl) carbamate
1 H NMR(600MHz,CDCl 3 )δ8.26(d,J＝4.2Hz,1H),7.55(d,J＝7.4Hz,1H),7.07(dd,J＝7.4,4.9Hz,1H),4.93(d,J＝9.5Hz,1H),2.41-2.34(m,1H),2.32(s,3H),1.93-1.86(m,1H),1.79-1.71(m,1H),1.68(t,J＝4.4Hz,1H),1.33-1.22(m,2H),1.11(dd,J＝13.8,3.3Hz,1H),0.91(s,3H),0.88(s,6H)； 13 C NMR(151MHz,CDCl 3 )δ154.2,149.5,145.6,139.9,127.4,121.1,81.2,48.9,47.9,44.9,36.7,28.1,27.1,19.8,18.9,18.1,13.6
Example 12: menthol- (3-methylpyridin-2-yl) carbamic acid ester
1 H NMR(600MHz,CDCl 3 )δ8.25(d,J＝4.2Hz,1H),7.54(d,J＝7.3Hz,1H),7.06(dd,J＝7.4,4.9Hz,1H),4.66(td,J＝10.9,4.4Hz,1H),2.30(s,3H),2.11(d,J＝11.9Hz,1H),2.02-1.91(m,1H),1.74-1.62(m,2H),1.55-1.43(m,1H),1.42-1.32(m,1H),1.12-1.00(m,2H),0.95-0.88(m,7H),0.80(d,J＝6.9Hz,3H)； 13 C NMR(151MHz,CDCl 3 )δ153.4,149.6,145.7,139.9,127.1,121.0,75.5,47.4,41.3,34.3,31.4,26.3,23.6,22.1,20.8,18.0,16.5.
Example 13: cholesterol- (3-methylpyridin-2-yl) carbamate
1 H NMR(600MHz,CDCl 3 )δ8.25(d,J＝3.5Hz,1H),7.55(d,J＝7.2Hz,1H),7.10-7.01(m,1H),5.39(s,1H),4.65-4.55(m,1H),2.48-2.40(m,1H),2.39-2.32(m,1H),2.31(s,3H),2.04-1.92(m,3H),1.91-1.79(m,2H),1.67-1.41(m,8H),1.40-1.30(m,3H),1.29-1.22(m,2H),1.18-1.05(m,7H),1.03(s,3H),1.01-0.95(m,2H),0.92(d,J＝6.4Hz,3H),0.86(dd,J＝6.5,2.4Hz,6H),0.68(s,3H)； 13 C NMR(151MHz,CDCl 3 )δ153.1,149.5,145.6,139.9,139.7,127.0,122.7,121.0,75.4,56.7,56.2,50.1,42.3,39.8,39.5,38.4,37.0,36.6,36.2,35.8,31.9,31.9,28.2,28.0,24.3,23.9,22.8,22.6,21.1,19.4,18.7,18.0,11.9.
Claims (4)
1. A method for synthesizing a carbamate compound by utilizing an esterification reaction of amide and alcohol at room temperature is characterized by comprising the following steps: the method comprises the following steps:
s1, dissolving amide, a transition metal catalyst and alcohol in an organic solvent to obtain a mixed solution A, wherein the chemical reaction equation is as follows;
r in the carbamate compound 1 HetAr is as defined in the starting materials;
the amide isWherein R is n＝1,2,3,4,5,6；/>n＝1,2,3,4,5,6；/>X＝-CN,-NO 2 ,-F,-Cl,-Br,-I,-OH,-OCH 3 ,-OC 2 H 5 ,-SH,-NH 2 ,-SO 3 H,-COOH,-COOCH 3 ,-COOC 2 H 5 ,-CONH 2 ,-CONHCH 3 ,-COCH 3 ,-COC 2 H 5 -CHO; wherein hetAr is
The alcohol is R 1 OH, wherein R is 1 Is thatn＝0,1,2,3,4,5,6；/>n＝0,1,2,3,4,5,6；n＝0,1,2,3,4,5,6；/>n＝0,1,2,3,4,5,6，
S2, stirring the mixed solution A at room temperature for 1-6 hours to obtain mixed solution B;
s3, filtering the mixed solution B, concentrating the filtrate, and performing column chromatography to obtain the carbamate compound;
the reaction uses oxygen in the air as an oxidant;
the transition metal catalyst is copper chloride, copper acetate, palladium acetate, copper sulfate, palladium trifluoroacetate or palladium chloride.
2. The method for synthesizing a carbamate compound by an esterification reaction of an amide and an alcohol at room temperature according to claim 1, wherein: the organic solvent is acetonitrile, dichloromethane, dichloroethane, tetrahydrofuran, toluene, chlorobenzene, chloroform, N-dimethylformamide, and dimethyl sulfoxide.
3. The method for synthesizing a carbamate compound by an esterification reaction of an amide and an alcohol at room temperature according to claim 1, wherein: the molar ratio of the amide to the transition metal catalyst is 1:0.02 to 0.5.
4. The method for synthesizing a carbamate compound by an esterification reaction of an amide and an alcohol at room temperature according to claim 1, wherein: the molar ratio of the amide to the alcohol is 1:1 to 4.
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| CN104744356A (en) * | 2015-03-24 | 2015-07-01 | 上海大学 | Synthesis method of disubstituted urea compounds |
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