CN104829493A - Synthetic method for romatic carbamic acid ester - Google Patents
Synthetic method for romatic carbamic acid ester Download PDFInfo
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Abstract
The invention relates to a synthetic method for romatic carbamic acid ester. The method comprises the following steps: adding diaryliodonium salt, amine, alkali and an organic solvent into a high-pressure reaction kettle, wherein diaryliodonium salt and amine are as raw materials, alkali is used as an accelerator and the organic solvent is used as a solvent; introducing carbon dioxide, and carrying out reaction under stirring at 40 to 150 DEGC for 2 to 24 hours; when the reaction is completed, carrying out cooling to room temperature, then slowly releasing unreacted carbon dioxide to normal pressure, filtering reaction liquid, and carrying out pressure reduced evaporation to remove the solvent so as to obtain a crude product; and carrying out purifying through column chromatography so as to obtain a series of romatic carbamic acid ester compounds. The synthetic method for the romatic carbamic acid ester provided by the invention avoids usage of phosgene or isocyanate, is simple and safe in operation and friendly to the environment, has wide substrate applicability and high yield, employs reusable raw materials, is beneficial for industrial production and has an extensive application scope in pesticides, medicines and natural product syntheses.
Description
Technical field
The present invention relates to medication chemistry synthesis technical field, be specifically related to a kind of method of synthesizing amino formic acid aromatic ester.
Background technology
Carboxylamine aromatic ester chemical combination material is a class general formula is the compound of RNHCOOAr, and in formula, R is hydrogen, aliphatic radical or aryl, and Ar is aryl or heteroaryl.Carboxylamine aromatic ester is the basic framework of a lot of natural product, as Physostigmine, has important biological activity.Carboxylamine aromatic ester plays effect greatly in agriculture production, is widely used as sterilant, miticide, weedicide and sterilant etc. (as carbofuran, F-1991, Herba ainsliaeae yunnanensis etc.); It is applied widely pharmaceutically have also been obtained, and the Exelon being such as used for the treatment of Alzheimer's disease belongs to a kind of carboxylamine aromatic ester compound exactly.In addition, carboxylamine aromatic ester is also important synthetic intermediate and industrial chemicals, has important purposes in organic synthesis.
The synthesis of carboxylamine aromatic ester compound has following several method traditionally: (1) is by chloroformic acid aromatic ester and ammonia or amine Reactive Synthesis; (2) by urea chloride and phenol Reactive Synthesis (K.W.Quasdorf, M.Riener, K.V.Petrova, N.K.Garg, J.Am.Chem.Soc.2009,131,17748 – 17749); (3) carboxylamine aromatic ester also can be obtained by reacting by isocyanic ester and phenol.It is to be noted, chloroformic acid aromatic ester, urea chloride and isocyanic ester that above three kinds of methods use are all obtain using hypertoxic phosgene as Material synthesis, the safety of the environmental pollution easily caused in production process, serious threat people, so be subject to great restriction (S.Ozaki in industrial application, Chem.Rev.1972,72,457-496; R.A.Batey, V.Santhakumar, C.Y.Ishii, S.D.Taylor, Tetrahedron Lett.1998,39,6267-6270).Therefore, the synthetic method of the carboxylamine aromatic ester of development environment close friend is subject to the extensive concern of scientific circles and industry member always.
At present about the report of non-phosgene synthesis carboxylamine aromatic ester is little, most study be utilize the phenol of methane amide and 2-carbonyl substituted that oxidative coupling reaction occurs under the catalysis of copper to carry out synthesizing amino formic acid aromatic ester (G.S.Kumar, C.U.Maheswari, R.A.Kumar, M.L.Kantam, K.R.Reddy, Angew.Chem.Int.Ed.2011,50,11748-11751; N.T.S.Phan, T.T.Nguyen, P.H.L.Vu, ChemCatChem 2013,5,3068-3077), but the substrate spectrum that the method is suitable for is little, and the phenol of 2-carbonyl substituted is not easy to obtain.
Carbonic acid gas is due to its rich content on earth, low price, the feature such as nontoxic, reproducible, phosgene is replaced to cause everybody great interest as the raw material of synthesis of carbamates with it, can realize utilizing carbonic acid gas for raw material is by the alkyl carbamate (W.McGhee corresponding to the Reactive Synthesis such as alcohol, alkynol that amine and Terminal Acetylenes, ethyl vinyl ether, fatty alcohol, halogenated aliphatic hydrocarbon, ortho-formiate, epoxide, Ts protect at present, D.Riley, K.Christ, Y.Pan, B.Parnas, J.Org.Chem.1995,60,2820-2830; M.Abla, J.-C.Choi, T.Sakakura, Chem.Commun.2001,2238-2239; J.M.Hooker, A.T.Reibel, S.M.Hill, M.J.Schueller, J.S.Fowler, Angew.Chem.Int.Ed.2009,48,3482-3485; S.L.Peterson, S.M.Stucka, C.J.Dinsmore, Org.Lett.2010,12,1340-1343; Y.Takeda, S.Okumura, S.Tone, I.Sasaki, S.Minakata, Org.Lett.2012,14,4874-4877; D.Chaturvedi, Tetrahedron 2012,68,15-45).But also do not utilize carbonic acid gas for the report of raw material direct synthesizing amino formic acid aromatic ester at present.
Summary of the invention
The invention provides a kind of novel method of synthesizing amino formic acid aromatic ester, the method operational safety is simple, and be raw material with carbonic acid gas, do not need transition-metal catalyst, environmental friendliness, the aryl iodide by product produced in reaction process can be used as the raw material recycling of synthesis of diaryl salt compounded of iodine, cost-saving, is conducive to industrial production.
Principle of the present invention is with carbonic acid gas, amine and high price salt compounded of iodine for raw material, under the promotion of alkali, three components reaction one-step synthesis carboxylamine aromatic ester occurs.The method take carbonic acid gas as raw material, environmentally friendly, and method is simple, and operational safety, has potential practical value.
Object of the present invention is achieved through the following technical solutions:
A method for synthesizing amino formic acid aromatic ester, in autoclave, adds diaryl group iodized salt and amine as raw material, alkali is promotor, be solvent with organic solvent, pass into carbonic acid gas, stirring reaction 2 ~ 24 hours at 40 ~ 150 DEG C, room temperature is cooled to after reaction terminates, the carbonic acid gas that release is not reacted is to normal pressure, and reacting liquid filtering, removes solvent under reduced pressure and obtain crude product, to purify the carboxylamine aromatic ester compound obtained described in series through column chromatography, its reaction is shown below:
Wherein, Ar
1, Ar
2comprise phenyl, to bromophenyl, a bromophenyl, o-bromophenyl, rubigan, between chloro-phenyl-, Chloro-O-Phenyl, p-methylphenyl, to cyano-phenyl, adjacent cyano-phenyl, between cyano-phenyl, p-trifluoromethyl phenyl, p-nitrophenyl, O-Nitrophenylfluorone, m-nitro base, to tert-butyl-phenyl, o-isopropyl phenyl, an aminomethyl phenyl, o-methyl-phenyl-, 2,5-3,5-dimethylphenyl, 2,4,6 – trimethylphenyls, 2,4,6 – triisopropyl phenyl or p-methoxyphenyls;
X comprises trifluoromethanesulfonic acid base, tosic acid base, Tetrafluoroboric acid base, chlorine or bromine;
R
1, R
2comprise hydrogen, methyl, ethyl, propyl group, sec.-propyl, cyclohexyl, normal-butyl, benzyl or allyl group; Or
for Pyrrolidine, hexahydropyridine or morpholine.
In aforesaid method, autoclave adopts gap type high-pressure reactor or continuous high pressure reactor.
In aforesaid method, the mol ratio of diaryl group iodized salt and amine is 1:(1 ~ 10).
In aforesaid method, alkali is sodium carbonate, salt of wormwood, cesium carbonate, sodium hydroxide, sodium methylate, potassium tert.-butoxide, sodium tert-butoxide, trimethyl carbinol lithium, Isosorbide-5-Nitrae-diazabicylo [2.2.2] octane or 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene.
In aforesaid method, the mol ratio of the amount and diaryl group iodized salt that add alkali is (1 ~ 3): 1.
In aforesaid method, solvent is the one in acetonitrile, tetrahydrofuran (THF), DMF, dimethyl sulfoxide (DMSO), methyl alcohol.
In aforesaid method, the pressure of carbonic acid gas is 0.2 ~ 8MPa.
In aforesaid method, reaction terminates rear employing column chromatography by product separation purifying; Described column chromatography elutriant is the mixed solvent of sherwood oil and ethyl acetate.Described column chromatography elutriant is the mixed solvent of sherwood oil and ethyl acetate, and the volume ratio between sherwood oil and ethyl acetate is (10 ~ 30): 1.
The present invention has the following advantages and effect relative to existing technology:
The synthetic method of carboxylamine aromatic ester of the present invention raw materials used nontoxic, easily obtain, react good to functional group adaptability, to substrate wide adaptability, by product aryl iodide compound can reclaim again as the raw material of synthesis of diaryl salt compounded of iodine, can save production cost, and simple to operate, safety, reaction conditions is gentle, thus has good prospects for commercial application.
Accompanying drawing explanation
Fig. 1 is embodiment 1-7 products therefrom hydrogen spectrogram;
Fig. 2 is embodiment 1-7 products therefrom carbon spectrogram;
Fig. 3 is embodiment 8 products therefrom hydrogen spectrogram;
Fig. 4 is embodiment 8 products therefrom carbon spectrogram;
Fig. 5 is embodiment 9 products therefrom hydrogen spectrogram;
Fig. 6 is embodiment 9 products therefrom carbon spectrogram;
Fig. 7 is embodiment 10 products therefrom hydrogen spectrogram;
Fig. 8 is embodiment 10 products therefrom carbon spectrogram;
Fig. 9 is embodiment 11 products therefrom hydrogen spectrogram;
Figure 10 is embodiment 11 products therefrom carbon spectrogram;
Figure 11 is embodiment 12 products therefrom hydrogen spectrogram;
Figure 12 is embodiment 12 products therefrom carbon spectrogram;
Figure 13 is embodiment 13 products therefrom hydrogen spectrogram;
Figure 14 is embodiment 13 products therefrom carbon spectrogram;
Figure 15 is embodiment 14 products therefrom hydrogen spectrogram;
Figure 16 is embodiment 14 products therefrom carbon spectrogram;
Figure 17 is embodiment 15 products therefrom hydrogen spectrogram;
Figure 18 is embodiment 15 products therefrom carbon spectrogram;
Figure 19 is embodiment 16 products therefrom hydrogen spectrogram;
Figure 20 is embodiment 16 products therefrom carbon spectrogram.
Embodiment
Below in conjunction with specific embodiments and the drawings, the present invention is described in further detail, but the substrate of embodiments of the present invention and adaptation is not limited thereto.
Embodiment 1
0.25 mmole two (2 is added in autoclave, 4,6-trimethylphenyl) iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene (DBU), 3 milliliters of DMF, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 72%.
Embodiment 2
0.25 mmole two (2 is added in autoclave, 4,6-trimethylphenyl) iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole Isosorbide-5-Nitrae-diazabicylo [2.2.2] octane (DABCO), 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 63%.
Embodiment 3
0.25 mmole two (2 is added in autoclave, 4,6-trimethylphenyl) iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene (DBU), 3 milliliters of acetonitriles, are filled with the CO of 0.7MPa
2, at 40 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 41%.
Embodiment 4
In autoclave, add 0.25 mmole two (2,4,6-trimethylphenyl) iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 86%.
Embodiment 5
In autoclave, add 0.25 mmole two (2,4,6-trimethylphenyl) iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole triethylamine, 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 67%.
Embodiment 6
In autoclave, add 0.25 mmole two (2,4,6-trimethylphenyl) iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole DBU, 3 milliliters of THF, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 70%.
Embodiment 7
In autoclave, add 0.25 mmole two (2,4,6-trimethylphenyl) iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 0.75MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 75%.
The structural characterization data of embodiment 1-7 products therefrom are as follows (nuclear magnetic spectrogram is as depicted in figs. 1 and 2):
1H NMR(400MHz,CDCl
3):δ＝6.74(s,2H),3.42–3.34(m,2H),3.32–3.25(m,2H),2.15(s,3H),2.05(s,6H),1.18(t,J＝6.83H),1.10(t,J＝6.8,3H).
13C NMR(100MHz,CDCl
3):δ＝146.4,139.3,127.4,123.1,121.9,35.1,34.7,13.6,9.1,7.2,6.3.
IR(KBr):2976,2926,2868,1720,1470,1415,1378,1314,1275,1199,1158,1095,1040,963,858(cm
-1).
MS(EI):m/z(％)＝235[M
+],135,100(100),72.
HRMS-ESI(m/z):calcd for C
14H
22NO
2(M+H)
+:236.1645,found:236.1651.
As follows according to the structure of above inferred from input data products therefrom:
Embodiment 8
0.25 mmole 2-methyl-4 is added in autoclave '-methoxyl group phenylbenzene iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 43%.
The structural characterization data of embodiment 8 products therefrom are as follows (nuclear magnetic spectrogram is as shown in Figure 3 and Figure 4):
1H NMR(400MHz,CDCl
3):δ＝7.24–7.15(m,2H),7.14–7.03(m,2H),3.52–3.36(m,7.1,4H),2.23(s,3H),1.31–1.19(m,6H).
13C NMR(100MHz,CDCl
3):δ＝154.0,150.0,130.9,130.4,126.7,125.3,122.2,42.2,41.9,16.3,14.3,13.4.
IR(KBr):2977,2931,2879,1722,1631,1469,1417,1378,1274,1225,1183,1154,1112,1041,962,750(cm
-1).
MS(EI):m/z(％)＝207[M
+],151,100(100),77,72.
HRMS-ESI(m/z):calcd for C
12H
18NO
2(M+H)
+:208.1332,found:208.1332.
As follows according to the structure of above inferred from input data products therefrom
Embodiment 9
0.25 mmole 3-methyl-4 is added in autoclave '-methoxyl group phenylbenzene iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 54%.
The structural characterization data of embodiment 9 products therefrom are as follows (nuclear magnetic spectrogram is as shown in Figure 5 and Figure 6):
1H NMR(400MHz,CDCl
3):δ＝7.25–7.20(m,1H),6.99(d,J＝7.5,1H),6.97–6.87(m,2H),3.46–3.36(m,4H),2.35(s,3H),1.26–1.18(m,6H).
13C NMR(100MHz,CDCl
3):δ＝154.4,151.5,139.3,128.9,125.9,122.4,118.7,42.2,41.9,21.3,14.2,13.4.
IR(KBr):2972,2929,2874,1721,1610,1469,1415,1244,1159,964,762,687(cm
-1).
MS(EI):m/z(％)＝207[M
+],151,100(100),77,72.
HRMS-ESI(m/z):calcd for C
12H
18NO
2(M+H)
+:208.1332,found:208.1330.
As follows according to the structure of above inferred from input data products therefrom:
Embodiment 10
0.25 mmole 4-methyl-4 is added in autoclave '-methoxyl group phenylbenzene iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 30%.
The structural characterization data of embodiment 10 products therefrom are as follows (nuclear magnetic spectrogram is as shown in Figure 7 and Figure 8):
1H NMR(400MHz,CDCl
3):δ＝7.14(d,J＝8.0,2H),6.99(d,J＝8.0,2H),3.46–3.36(m,4H),2.33(s,3H),1.26–1.17(m,6H).
13C NMR(100MHz,CDCl
3):δ＝154.5,149.3,134.5,129.7,121.4,42.2,41.8,20.8,14.2,13.4.
IR(KBr):2978,2934,1720,1512,1472,1417,1273,1206,1155,1099,961(cm
-1).
MS(EI):m/z(％)＝207[M
+],151,100(100),77,72.
HRMS-ESI(m/z):calcd for C
12H
18NO
2(M+H)
+:208.1332,found:208.1332.
As follows according to the structure of above inferred from input data products therefrom:
Embodiment 11
In autoclave, add 0.25 mmole phenylbenzene iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 80%.
The structural characterization data of embodiment 11 products therefrom are as follows (nuclear magnetic spectrogram is as shown in Figure 9 and Figure 10):
1H NMR(400MHz,CDCl
3):δ＝7.35(t,J＝7.7,2H),7.18(t,J＝7.4,1H),7.12(d,J＝7.7,2H),3.48–3.35(m,4H),1.29–1.18(m,6H).
13C NMR(100MHz,CDCl
3):δ＝154.2,151.5,129.1,125.0,121.7,42.2,41.9,14.2,13.4.
IR(KBr):2977,2933,1721,1470,1419,1273,1205,1158,1097,961,747,689(cm
-1).
MS(EI):m/z(％)＝193[M
+],149,100(100),72.
HRMS ESI(m/z):calcd for C
11H
15NO
2Na(M+Na)
+:216.0995,found:216.1001.
As follows according to the structure of above inferred from input data products therefrom:
Embodiment 12
In autoclave, add 0.25 mmole two (2,4,6-trimethylphenyl) iodine fluoroform sulphonate, 1.25 mmole methylamines, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 62%.
The structural characterization data of embodiment 12 products therefrom are as follows (nuclear magnetic spectrogram is as is illustrated by figs. 11 and 12):
1H NMR(400MHz,CDCl
3):δ＝6.85(s,2H),5.04(br,1H),2.99–2.84(m,3H),2.26(s,3H),2.15(s,6H).
13C NMR(100MHz,CDCl
3):δ＝154.8,145.8,134.9,130.5,129.1,27.8,20.7,16.1.
IR(KBr):2919,2851,1706,1536,1481,1267,1199,1146,937,852(cm
-1).
MS(EI):m/z(％)＝193[M
+],136(100),121,91,77.
HRMS-ESI(m/z):calcd for C
11H
16NO
2(M+H)
+:194.1176,found:194.1170.
As follows according to the structure of above inferred from input data products therefrom:
Embodiment 13
0.25 mmole 2 – sec.-propyl-4 is added in autoclave '-methoxyl group phenylbenzene iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 80%.
The structural characterization data of embodiment 13 products therefrom are as follows (nuclear magnetic spectrogram is as shown in Figure 13 and Figure 14):
1H NMR(400MHz,CDCl
3):δ＝7.33–7.23(m,1H),7.22–7.14(m,2H),7.10–7.04(m,1H),3.52–3.38(m,4H),3.17–3.07(m,1H),1.29–1.20(m,12H).
13C NMR(100MHz,CDCl
3):δ＝154.3,148.8,140.3,126.4,126.2,125.5,122.5,42.1,41.8,27.3,22.8,14.2,13.4.
IR(KBr):2968,2931,2872,1725,1418,1273,1220,1186,1155,1083,962,753(cm
-1).
MS(EI):m/z(％)＝235[M
+],100(100),72.
HRMS-ESI(m/z):calcd for C
14H
22NO
2(M+H)
+:236.1645,found:236.1646.
As follows according to the structure of above inferred from input data products therefrom:
Embodiment 14
In autoclave, add 0.25 mmole 4 – nitro phenylbenzene iodide ion fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 86%.
The structural characterization data of embodiment 14 products therefrom are as follows (nuclear magnetic spectrogram is as shown in Figure 15 and Figure 16):
1H NMR(400MHz,CDCl
3):δ＝8.23(d,J＝7.9,2H),7.30(d,J＝7.9,2H),3.48–3.37(m,4H),1.28–1.19(m,6H).
13C NMR(100MHz,CDCl
3):δ＝156.5,152.7,144.6,125.0,122.2,42.5,42.1,14.2,13.2.
IR(KBr):2978,2934,1728,1523,1469,1418,1346,1272,1233,1209,1149,957,861,746(cm
-1).
MS(EI):m/z(％)＝238[M
+],100(100),72.
HRMS ESI(m/z):calcd for C
11H
14N
2O
4Na(M+Na)
+:261.0846,found:261.0846.
As follows according to the structure of above inferred from input data products therefrom:
Embodiment 15
In autoclave, add 0.25 mmole two (2,4,6-trimethylphenyl) iodine fluoroform sulphonate, 1.25 mmole morpholines, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 0.75MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 30:1: ethyl acetate mixed solvent, productive rate 90%.
The structural characterization data of embodiment 15 products therefrom are as follows (nuclear magnetic spectrogram is as shown in Figure 17 and Figure 18):
1H NMR(400MHz,CDCl
3):δ＝6.86(s,2H),3.78–3.73(m,5H),3.71–3.56(m,3H),2.27(s,3H),2.15(s,6H).
13C NMR(100MHz,CDCl
3):δ＝153.1,146.1,134.9,130.0,129.1,66.7,45.0,44.2,20.7,16.1.
IR(KBr):2921,2854,1722,1415,1276,1241,1195,1146,1116,1061,1020,858,755.
MS(EI):m/z(％)＝249[M
+],135,114(100),91,70.
HRMS ESI(m/z):calcd for C
14H
20NO
3(M+H)
+:250.1438,found:250.1438.
Embodiment 16
In autoclave, add 0.25 mmole 4 – bromo-4 '-methoxyl group phenylbenzene iodine fluoroform sulphonate, 2.5 mmole diethylamine, 0.5 mmole DBU, 3 milliliters of acetonitriles, are filled with the CO of 4MPa
2, at 80 DEG C of stirring reactions after 12 hours, stop heating and stir, being cooled to room temperature, the unreacted CO of slow emptying
2.Extraction into ethyl acetate reaction solution, vacuum rotary steam removes solvent, then by column chromatographic isolation and purification, obtains target product, the sherwood oil of column chromatography elutriant used to be volume ratio be 20:1: ethyl acetate mixed solvent, productive rate 20%.
The structural characterization data of embodiment 16 products therefrom are as follows (nuclear magnetic spectrogram is as illustrated in figures 19 and 20):
1H NMR(400MHz,CDCl
3):δ＝7.46(d,J＝8.7,2H),7.01(d,J＝8.7,2H),3.46–3.34(m,4H),1.26–1.17(m,6H).
13C NMR(100MHz,CDCl
3):δ＝153.8,150.6,132.2,123.6,118.0,42.3,41.9,14.2,13.3.
IR(KBr):2976,2932,1724,1523,1475,1419,1274,1208,1153,1069,960,860,750.
MS(EI):m/z(％)＝271[M
+],256,183,100(100).
HRMS ESI(m/z):calcd for C
11H
14BrNO
2Na
+(M+Na)
+:294.0100,found:294.0106.
The above embodiment of the present invention is only for example of the present invention is clearly described, and is not the restriction to embodiments of the present invention.For those of ordinary skill in the field, can also make other changes in different forms on the basis of the above description.Here exhaustive without the need to also giving all embodiments.All any amendments done within the spirit and principles in the present invention, equivalent to replace and improvement etc., within the protection domain that all should be included in the claims in the present invention.
Claims (8)
1. the method for a synthesizing amino formic acid aromatic ester, it is characterized in that, in autoclave, add diaryl group iodized salt and amine as raw material, alkali is promotor, take organic solvent as solvent, pass into carbonic acid gas, stirring reaction 2 ~ 24 hours at 40 ~ 150 DEG C, is cooled to room temperature after reaction terminates, and the carbonic acid gas that release is not reacted is to normal pressure, reacting liquid filtering, remove solvent under reduced pressure and obtain crude product, to purify the carboxylamine aromatic ester compound obtained described in series through column chromatography, its reaction is shown below:
Wherein, Ar
1, Ar
2comprise phenyl, to bromophenyl, a bromophenyl, o-bromophenyl, rubigan, between chloro-phenyl-, Chloro-O-Phenyl, p-methylphenyl, to cyano-phenyl, adjacent cyano-phenyl, between cyano-phenyl, p-trifluoromethyl phenyl, p-nitrophenyl, O-Nitrophenylfluorone, m-nitro base, to tert-butyl-phenyl, o-isopropyl phenyl, an aminomethyl phenyl, o-methyl-phenyl-, 2,5-3,5-dimethylphenyl, 2,4,6 – trimethylphenyls, 2,4,6 – triisopropyl phenyl or p-methoxyphenyls;
X comprises trifluoromethanesulfonic acid base, tosic acid base, Tetrafluoroboric acid base, chlorine or bromine;
R
1, R
2comprise hydrogen, methyl, ethyl, propyl group, sec.-propyl, cyclohexyl, normal-butyl, benzyl or allyl group; Or
for Pyrrolidine, hexahydropyridine or morpholine.
2. the method for synthesizing amino formic acid aromatic ester according to claim 1, is characterized in that, autoclave adopts gap type high-pressure reactor or continuous high pressure reactor.
3. the method for synthesizing amino formic acid aromatic ester according to claim 1, is characterized in that, the mol ratio of diaryl group iodized salt and amine is 1:(1 ~ 10).
4. the method for synthesizing amino formic acid aromatic ester according to claim 1, it is characterized in that, alkali is sodium carbonate, salt of wormwood, cesium carbonate, sodium hydroxide, sodium methylate, potassium tert.-butoxide, sodium tert-butoxide, trimethyl carbinol lithium, 1,4-diazabicylo [2.2.2] octane or 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene.
5. the method for synthesizing amino formic acid aromatic ester according to claim 4, is characterized in that: the mol ratio of the amount and diaryl group iodized salt that add alkali is (1 ~ 3): 1.
6. the method for synthesizing amino formic acid aromatic ester according to claim 1, is characterized in that: solvent is the one in acetonitrile, tetrahydrofuran (THF), DMF, dimethyl sulfoxide (DMSO), methyl alcohol.
7. the method for synthesizing amino formic acid aromatic ester according to claim 1, is characterized in that: the pressure of carbonic acid gas is 0.2 ~ 8MPa.
8. the method for synthesizing amino formic acid aromatic ester according to claim 1, is characterized in that, reaction terminates rear employing column chromatography by product separation purifying; Described column chromatography elutriant is the mixed solvent of sherwood oil and ethyl acetate.Described column chromatography elutriant is the mixed solvent of sherwood oil and ethyl acetate, and the volume ratio between sherwood oil and ethyl acetate is (10 ~ 30): 1.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106220533A (en) * | 2016-08-13 | 2016-12-14 | 华南理工大学 | A kind of utilize ketone, amine and the method for carbon dioxide synthesis of carbamates |
| CN107674044A (en) * | 2017-09-30 | 2018-02-09 | 华南理工大学 | A kind of method using carbon dioxide, amine and aryldiazonium acetic acid esters synthesis of carbamates |
| CN110028435A (en) * | 2019-04-01 | 2019-07-19 | 浙江工业大学 | A method of synthesis 3- formic acid esters -2- pyrrolines |
| CN110156721A (en) * | 2019-05-16 | 2019-08-23 | 华南理工大学 | Utilize diazotate, cyclic ethers, amine and CO2The method of synthesis of carbamates |
| CN112920004A (en) * | 2021-01-19 | 2021-06-08 | 华南理工大学 | Beta-iodoalkenyl carbamate compound and preparation method and application thereof |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5144634A (en) * | 1974-10-15 | 1976-04-16 | Mitsubishi Chem Ind | TEIKO SEITSUMAGUROYOKOBAI YOSATSUCHUZAI |
| CN104355955A (en) * | 2014-10-20 | 2015-02-18 | 华南理工大学 | Method for synthetizing carbamate |
-
2015
- 2015-04-20 CN CN201510189518.9A patent/CN104829493B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5144634A (en) * | 1974-10-15 | 1976-04-16 | Mitsubishi Chem Ind | TEIKO SEITSUMAGUROYOKOBAI YOSATSUCHUZAI |
| CN104355955A (en) * | 2014-10-20 | 2015-02-18 | 华南理工大学 | Method for synthetizing carbamate |
Non-Patent Citations (4)
| Title |
|---|
| TARUN KANTI PRADHAN ET AL.: "Application of directed metalation in synthesis. Part 6: A novel anionic rearrangement under directed metalation conditions leading to heteroannulation", 《TETRAHEDRON》 * |
| YIGANG ZHAO ET AL.: "Beyond Directed ortho Metalation: Ru-Catalyzed CAr−O Activation/Cross-Coupling Reaction by Amide Chelation", 《JOURNAL OF THE AMERICAN SOCIETY》 * |
| YIGANG ZHAO ET AL.: "Beyond Directed ortho Metalation: Ru-Catalyzed CAr−O Activation/Cross-Coupling Reaction by Amide Chelation", 《JOURNAL OF THE AMERICAN SOCIETY》, vol. 136, 21 July 2014 (2014-07-21), pages 11224 - 11227 * |
| 戚朝荣等: "超临界二氧化碳介质中的有机反应", 《化学进展》 * |
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