CN114656369A - High allylamine compound, synthesis method and application thereof - Google Patents
High allylamine compound, synthesis method and application thereof Download PDFInfo
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- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
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- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
Abstract
The invention provides a high allylamine compound, a synthesis method and application thereof, belonging to the field of organic chemistry. Under the conditions of room temperature and inert gas protection, and in the presence of an organic photosensitizer and an electron donor, imine reacts with 1, 3-butadiene derivatives and halogenated alkane under blue light irradiation, and the high allylamine compound is obtained with high selectivity. The method has the advantages of mild reaction conditions, short reaction steps, simple post-treatment, and high stereoselectivity and regional selection of reaction products. Meanwhile, the method can be used for derivatization of natural products and post-modification of drug molecules.
Description
Technical Field
The invention belongs to the field of organic synthesis, and relates to a high allylamine compound, a synthesis method and application thereof.
Background
The homoallylamine compounds are important components for synthesizing various medicaments and natural substances with biological activity. The addition of allyl metal complexes to the carbon-nitrogen double bond of imines is one of the most efficient methods for obtaining homoallylic amines, which has promoted the rapid development of synthetic and pharmaceutical chemistry over the last decades. However, the process of preparation relying on preactivated allylhalohydrocarbons and stoichiometric amounts of metal reducing agents is cumbersome and uneconomical and results in environmental pollution and waste of resources. Therefore, the simple, economical and environment-friendly synthesis method of the high allylamine compound is developed, and the high allylamine compound is applied to the synthesis of natural substances with biological activity and has great promotion effect on synthetic chemistry and pharmaceutical chemistry.
Disclosure of Invention
The invention provides a high allylamine compound, a synthesis method and application thereof.
The technical scheme adopted by the invention is as follows:
a high allylamine compound has the following structure:
wherein Ar is2Is a substituted phenyl group; ar (Ar)1Is substituted phenyl or heterocyclyl;
R1selected from hydrogen, C1-C6 primary alkyl, C1-C6 secondary alkyl, C1-C6 tertiary alkyl, cycloalkane or heterocompoundA cycloalkyl group;
R2selected from hydrogen, primary alkyl groups of C1-C6, secondary alkyl groups of C1-C6, tertiary alkyl groups of C1-C6, cycloalkane or heterocycloalkyl radicals;
R3selected from hydrogen, C1-C6 primary alkyl, C1-C6 secondary alkyl, C1-C6 tertiary alkyl, cycloalkane or heterocycloalkane;
r4 is selected from hydrogen, C1-C6 primary alkyl, C1-C6 secondary alkyl, C1-C6 tertiary alkyl, cycloalkane or heterocycloalkane;
r5 is selected from hydrogen, C1-C6 primary alkyl, C1-C6 secondary alkyl, C1-C6 tertiary alkyl, cycloalkane or heterocycloalkane;
the substituent in the substituted phenyl is selected from halogen, alkyl, alkoxy, alkoxycarbonyl or amino.
The invention also provides a synthetic method of the high allylamine compound, and the synthetic route is as follows:
the method comprises the following steps: under the conditions of room temperature and the protection of inert gases, illumination, the presence of an organic photosensitizer and an electron donor, the halogenated alkane 1 reacts with the 1, 3-butadiene derivative 2 and the imine 3 in a solvent to obtain the homoallylamine compound 4.
The organic photosensitizer may be 4 CzIPN.
The electron donor may be diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate (HE) or triethylamine.
The molar ratio of the halogenated alkane 1, the 1, 3-butadiene 2, the imine 3, the organic photosensitizer and the HE is 2.0:2.0:1.0:0.01: 2.0;
the molar ratio of the halogenated alkane 1, the 1, 3-butadiene 2, the imine 3, the organic photosensitizer and the triethylamine is 2.0:2.0:1.0:0.01: 4.0.
the solvent is Dichloroethane (DCE).
The method of the invention can be applied to derivatization of natural substances with biological activity or post-modification of drug molecules, based on homoallylic amination of various compounds and high-yield derivatization of natural active substances (such as lithocholic acid and estrone) or drug molecules (such as indomethacin and probenecid), and has a promoting effect on the development of synthetic chemistry and pharmaceutical chemistry.
The method is applicable to imine reaction substrates with similar structures, and has the advantages of high reaction yield and high selectivity. Meanwhile, the reaction has better application in derivatization of natural active substances and post-modification of drug molecules.
Drawings
FIG. 1 is a schematic representation of the imine quenched 4CzIPN of example 16.
FIG. 2 is a schematic representation of triethylamine quenched 4CzIPN in example 16.
FIG. 3 is a schematic representation of 3-iodooxetane quenched 4CzIPN of example 16.
In the figure: i is0Fluorescence intensity without addition of a quencher; i is the fluorescence intensity after addition of the quencher.
FIG. 4 is a graph showing the change of the main species in the fluorescence quenching reaction system of example 16.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to the following specific examples.
Exploration test of reaction conditions: (taking the example of the reaction of 2a, 1, 3-butadiene and 3a to give 5 a)
Typically, compound 2a (2.0mmol), 1, 3-butadiene (2.0mmol), compound 3a (1.0mmol), 4CzIPN (0.01mmol), HE (2.0mmol) and 5mL DCE were mixed and reacted by irradiation with a 10W 450nm LED lamp at room temperature under inert gas protection for 4h, and the complete disappearance of the starting material 3a was monitored by thin layer plate (TLC) (4 h); the solvent was dried by spin-drying and column chromatography (eluent petroleum ether/ethyl acetate 20/1) gave colorless liquid 4 a.
The reaction equation is as follows:
TABLE 1
| Numbering | Reaction conditions | 4a yield/% |
| 1 | none | 89％ |
| 2 | No PC, | 40％ |
| 3 | No light | N.R |
| 4 | Ir-1instead of 4CzPIN | 88％ |
| 5 | Ir-2instead of 4CzPIN | 91％ |
| 6 | TEA instead of HE | N.R |
| 7 | DIPEA instead of HE | N.R |
| 8 | DBACO instead of HE | N.R |
| 9 | THF instead of DCE | 57％ |
| 10 | ACN instead of DCE | 71％ |
| 11 | DCM instead of DCE | 66％ |
| 12 | Under | 0 |
| 13 | No PC,400nm | 23％ |
As shown in the table, the boundary conditions of the reaction were investigated, and it was found that the target product was obtained in different yields under all other possible reaction conditions. Finally, the optimal reaction conditions are determined as follows: under the protection of inert gas at room temperature, 4CzIPN is used as photosensitizer, HE is used as electron donor, and the mixture is irradiated by a 450nm LED lamp in trichloroethane (DCE) solvent.
Example 1:
4a, the experimental procedures and purification methods were carried out with reference to the search experiment. RF 0.5(EA: PE 1:5), eluent: petroleum ether/ethyl acetate 10/1, 87% yield, product was a colorless liquid.
1H NMR(400MHz,CDCl3):δ7.18–7.07(m,2H),6.81(d,J＝8.7Hz,2H),6.74(s, 2H),5.55–5.43(m,1H),5.44–5.26(m,1H),4.10(dd,J＝7.7,5.9Hz,1H),3.78(s, 3H),3.24(s,1H),2.72–2.45(m,2H),2.27–2.17(m,7H),2.12(s,6H),1.43(s,9H). 13C NMR(101MHz,CDCl3):δ172.43,158.45,142.08,135.80,131.37,130.52, 129.44,129.06,127.84,127.47,113.57,80.07,61.15,55.13,39.95,35.26,28.06, 28.03,20.46,18.98.HRMS-ESI(m/z)[M+H]+calculated for C27H38NO3,424.2852, found:424.2841.
Example 2:
1H NMR(400MHz,CDCl3):δ7.24(dd,J＝26.8,8.4Hz,2H),7.13(d,J＝8.4Hz, 2H),6.74(dd,J＝128.5,48.0Hz,2H),5.61–5.44(m,1H),5.34(d,J＝7.1Hz,1H), 4.14(dt,J＝399.6,7.5,5.9Hz,1H),3.25(s,1H),2.57(ddd,J＝37.4,14.0,7.1Hz, 2H),2.21(d,J＝8.7Hz,7H),2.10(s,6H),1.43(s,9H).13C NMR(101MHz, CDCl3):δ172.34,142.22,132.48,132.05,130.76,130.40,129.56,128.91,128.33, 128.22,126.75,80.13,61.13,40.02,35.17,28.06,27.99,20.45,19.00.HRMS-ESI (m/z)[M+H]+calculated for C26H35ClNO2,428.2356,found:428.2344.
Example 3:
1H NMR(400MHz,CDCl3):δ7.39(d,J＝8.4Hz,2H),7.08(dd,J＝8.6,2.1Hz, 2H),6.74(s,2H),5.58–5.46(m,1H),5.39–5.28(m,1H),4.19–4.09(m,1H),3.25 (s,1H),2.55(dq,J＝36.8,7.1Hz,2H),2.20(d,J＝9.1Hz,7H),2.10(d,J＝4.4Hz, 6H),1.42(s,9H).13C NMR(101MHz,CDCl3):δ172.33,142.78,141.89,132.06, 131.25,130.67,129.54,128.82,128.55,126.70,120.56,80.12,61.10,40.02,35.14, 28.04,27.97,20.43,19.01.HRMS-ESI(m/z)[M+H]+calculated for C26H35BrNO2, 474.1831,found:474.1814.
Example 4:
1H NMR(400MHz,CDCl3):δ7.32–7.20(m,5H),6.76(s,2H),5.74–5.44(m, 1H),5.38(dd,J＝14.6,7.5Hz,1H),4.43–3.80(m,1H),3.29(s,1H),2.95–2.51 (m,2H),2.22(d,J＝4.0Hz,8H),2.13(s,5H),1.44(s,9H).13C NMR(101MHz, CDCl3):δ172.43,143.72,142.18,131.52,130.43,129.45,128.91,128.22,127.28, 126.84,126.77,80.08,61.70,40.02,35.24,28.05,20.46,18.99.HRMS-ESI(m/z) [M+H]+calculated for C26H36NO2,394.2746,found:394.2737.
Example 5:
1H NMR(400MHz,CDCl3):δ7.19–7.12(m,2H),7.01–6.92(m,2H),6.74(s, 2H),5.50(dddd,J＝15.4,7.7,4.5,1.2Hz,1H),5.38–5.29(m,1H),4.13(dd,J＝7.6, 5.9Hz,1H),3.21(s,1H),2.61(td,J＝7.6,6.9,4.1Hz,1H),2.55–2.47(m,1H), 2.29–2.16(m,7H),2.10(s,6H),1.42(s,9H).13C NMR(101MHz,CDCl3):δ 172.39,161.74(d,J＝244.8Hz),141.92,139.43(d,J＝2.0Hz),131.83,130.72, 129.51,129.02,128.29(d,J＝7.9Hz),126.99,115.09,114.88,80.13,61.05,40.06, 35.20,28.05,28.0,20.46,18.96.HRMS-ESI(m/z)[M+H]+calculated for C26H35NO2, 412.2652,found:412.2640.
Example 6:
1H NMR(400MHz,CDCl3):δ7.51(dd,J＝8.0,1.3Hz,1H),7.46(dd,J＝7.8,1.7 Hz,1H),7.31(td,J＝7.5,1.3Hz,1H),7.10(ddd,J＝7.9,7.3,1.7Hz,1H),6.77(s, 2H),5.64–5.50(m,1H),5.43–5.25(m,1H),4.71(t,J＝5.8Hz,1H),3.63(s,1H), 2.64–2.48(m,1H),2.32–2.22(m,4H),2.21(d,J＝2.7Hz,4H),2.17(s,6H),1.45 (s,9H).13C NMR(101MHz,CDCl3):δ172.35,143.41,142.69,132.71,132.64, 129.85,129.63,128.52,128.11,127.53,127.21,126.09,122.87,80.15,60.29,39.80, 35.13,28.04,20.36,19.17.HRMS-ESI(m/z)[M+H]+calculated for C26H35BrNO2, 472.1851,found:472.1842.
Example 7:
1H NMR(400MHz,CDCl3):δ7.39(d,J＝8.4Hz,1H),7.34(d,J＝2.1Hz,1H), 7.23(dd,J＝8.3,2.2Hz,1H),6.76(s,2H),5.62–5.50(m,1H),5.33–5.22(m,1H), 4.67(t,J＝5.7Hz,1H),3.56(s,1H),2.53(tq,J＝14.3,7.8Hz,2H),2.27–2.15(m, 7H),2.13(s,6H),1.43(s,9H).13C NMR(101MHz,CDCl3):δ172.31,142.52, 140.55,133.02,132.98,132.73,130.18,129.70,129.45,129.15,127.63,126.93, 125.72,80.22,57.85,39.50,35.09,28.06,28.02,20.37,19.12.HRMS-ESI(m/z) [M+H]+calculated for C26H34Cl2NO2,462.1967,found:462.1957.
Example 8:
1H NMR(400MHz,CDCl3):δ7.43(dd,J＝7.7,1.4Hz,1H),7.23(td,J＝7.5,1.7 Hz,1H),7.14(td,J＝7.3,1.4Hz,1H),7.11–7.08(m,1H),6.76(s,2H),5.56–5.44 (m,1H),5.39–5.26(m,1H),4.46(dd,J＝7.5,5.8Hz,1H),3.33(s,1H),2.61–2.45 (m,2H),2.22(s,6H),2.18(s,3H),2.15(d,J＝6.5Hz,7H),1.45(d,J＝8.1Hz,9H). 13C NMR(101MHz,CDCl3):δ172.41,142.58,142.52,135.16,131.56,130.29, 130.25,129.48,128.62,127.18,126.52,126.13,125.71,80.08,57.26,39.71,35.22, 28.03,28.00,20.43,19.27,18.90.HRMS-ESI(m/z)[M+H]+calculated for C27H38NO2,408.2903,found:408.2892.
Example 9:
1H NMR(400MHz,CDCl3):δ7.08(d,J＝2.7Hz,4H),6.74(s,2H),5.56–5.43(m, 1H),5.41–5.25(m,1H),4.13(dd,J＝7.6,5.9Hz,1H),3.24(s,1H),2.70–2.44(m, 1H),2.56(dtd,J＝21.3,13.9,13.5,6.2Hz,2H),2.31(d,J＝2.9Hz,3H),2.20(d,J＝ 4.7Hz,6H),2.11(d,J＝2.9Hz,6H),1.43(d,J＝9.2Hz,9H).13C NMR(101MHz, CDCl3):δ172.43,142.22,140.70,136.30,131.34,130.32,129.43,128.89,127.43, 126.64,80.05,61.38,40.03,35.24,28.04,21.02,20.44,19.01.HRMS-ESI(m/z) [M+H]+calculated for C27H38NO2,408.2903,found:408.2889.
Example 10:
1H NMR(400MHz,CDCl3):δ7.16(dd,J＝5.0,1.2Hz,1H),6.90(dd,J＝5.1,3.5 Hz,1H),6.77(s,2H),6.74(d,J＝3.4Hz,1H),5.60–5.42(m,2H),4.43–4.37(m, 1H),3.22(s,1H),2.75–2.54(m,2H),2.24(dd,J＝6.8,2.4Hz,4H),2.21(s,3H), 2.12(s,6H),1.43(s,9H).13C NMR(101MHz,CDCl3):δ172.51,147.98,141.62, 131.98,131.04,129.52,129.47,127.08,126.64,123.92,123.77,80.20,57.28,40.47, 35.24,28.14,28.10,20.58,18.79.HRMS-ESI(m/z)[M+H]+calculated for C24H34NO2S,400.2310,found:400.2300.
Example 11:
1H NMR(400MHz,CDCl3):δ7.56(dd,J＝7.9,1.2Hz,1H),7.37–7.29(dd,3H), 7.22(td,J＝7.5,1.2Hz,1H),7.10(td,J＝7.6,1.8Hz,1H),6.20(d,2H),5.56(dt,J＝ 15.0,6.5Hz,1H),5.42(dt,1H),4.78(ddd,J＝7.8,6.0,2.9Hz,2H),4.70(dt,J＝8.5, 4.5Hz,1H),4.35(t,J＝6.0Hz,2H),4.27(d,J＝4.2Hz,1H),3.02(tt,J＝7.6,5.9Hz, 1H),2.61(dt,J＝14.4,5.6Hz,1H),2.38(m,J＝11.7,6.9Hz,3H).13C NMR(101 MHz,CDCl3):δ146.30,141.05,137.70,133.10,130.91,128.69,127.81,127.55, 127.35,122.92,115.55,78.38,76.62,55.98,39.54,36.01,34.28.HRMS-ESI(m/z) [M+H]+calculated for C20H22BrINO,497.9929,found:497.9930.
Example 12: derivatization of lithocholic acid
Lithocholic acid is a secondary bile acid, also known as cholalic acid, 3 a-dihydroxy -carboxylic acid, and is present in higher vertebrate bile. The molecular structure of the bile acid contains both hydrophilic groups and hydrophobic groups, so that the spatial configuration of the bile acid has two properties of hydrophilicity and hydrophobicity, and the bile acid has strong interfacial activity. Meanwhile, lithocholic acid has more pharmacological activities, such as: inhibiting tumor growth, selectively killing breast cancer cells, and selectively inhibiting the activity of mammalian DNA polymerase.
The steps of the derivatization of lithocholic acid in the invention are as follows:
first, lithocholic acid is derivatized to an imine by reaction with an imine:
and reacting the derived imine with 1, 3-butadiene and an alkyl halide to obtain the homoallylic amine compound derived from lithocholic acid.
The experimental procedures and purification were carried out according to the search experiment. RF 0.5(EA: PE 1:2), eluent: petroleum ether/ethyl acetate 20/1, 51% yield, the product was a colorless liquid.
1H NMR(400MHz,CDCl3):δ7.30(dd,J＝8.6,3.6Hz,4H),7.02(d,J＝8.5Hz, 2H),6.30–6.23(m,2H),5.60(dt,J＝15.2,5.8Hz,1H),5.38(dt,J＝14.8,7.0Hz, 1H),4.29(d,J＝11.0Hz,2H),3.63(dt,J＝11.0,6.2Hz,1H),2.64–2.35(m,4H), 2.29(q,J＝1.7Hz,3H),2.03–1.71(m,9H),1.50(dd,J＝15.5,7.2Hz,3H),1.43(s, 15H),1.32–1.21(m,4H),1.21–1.03(m,5H),0.97(d,J＝6.3Hz,4H),0.92(s,3H), 0.66(s,3H).13C NMR(101MHz,CDCl3):172.75,172.33,149.69,146.76,140.34, 137.56,133.15,127.09,126.40,121.65,115.79,80.32,78.08,71.85,58.46,56.51(d, J＝4.3Hz),55.95,42.75,42.07,41.87,40.41,40.16,36.43,35.83,35.34,35.24, 34.55,31.37,30.94,30.53,28.22,28.10,27.17,26.39,24.19,23.35,20.81,18.29, 12.06.HRMS-ESI(m/z)[M+H]+calculated for C47H67INO5,852.4064,found: 852.4055.
Example 13: derivatization of estrone
Estrone, also known as feminone, is a white crystalline powder, soluble in ethanol and insoluble in water. Is obtained from pregnant woman urine or livestock ovary. It is the original hormone secreted by female animal ovary, has been used in clinic, is an important medical intermediate, is the intermediate of hormone ethinylestradiol for No. 1 contraceptive, and is mainly used for treating uterine hypoplasia, menstrual disorder, climacteric disturbance and the like.
The steps of the derivatization of estrone in the invention are as follows:
firstly, estrone reacts with 1, 3-diiodopropane to be derived into iodide:
and reacting the derived iodo product with 1, 3-butadiene and imine to obtain the homoallylic amine compound derived from estrone.
The experimental procedures and purification were carried out according to the search experiment. RF 0.5(EA: PE 1:4), eluent: petroleum ether/ethyl acetate 20/1, 58% yield, product was a colorless liquid.
1H NMR(400MHz,CDCl3):δ7.56(dd,J＝7.9,1.3Hz,1H),7.35(dd,J＝7.8,1.8 Hz,1H),7.31(dd,J＝8.7,3.4Hz,2H),7.22(ddd,J＝10.3,7.8,2.6Hz,2H),7.09 (dd,J＝7.6,1.8Hz,1H),6.71(dd,J＝8.6,2.7Hz,1H),6.65(d,J＝2.8Hz,1H), 6.19(d,J＝8.7Hz,2H),5.62(dt,J＝15.0,6.6Hz,1H),5.41(dt,J＝14.9,7.7Hz, 1H),4.68(dt,J＝8.7,4.3Hz,1H),4.29(d,J＝4.6Hz,1H),3.93(t,J＝6.4Hz,2H), 3.10–2.77(m,2H),2.70–2.58(m,1H),2.51(dd,J＝18.8,8.6Hz,1H),2.40(dd,J ＝8.0,4.9Hz,1H),2.36–2.24(m,2H),2.19–2.08(m,3H),2.08–1.93(m,3H), 1.82–1.72(m,2H),1.67–1.38(m,8H),0.92(s,3H).13C NMR(101MHz,CDCl3): δ157.02,146.41,141.24,137.70,137.64,134.67,133.06,131.91,128.61,127.79, 127.56,126.29,125.82,122.84,115.59,114.52,112.02,78.28,77.21,67.52,56.06, 50.36,47.98,43.94,39.55,38.33,35.84,32.15,31.54,29.63,28.71,26.53,25.89, 25.75,21.55.HRMS-ESI(m/z)[M+H]+calculated for C38H44BrINO2,752.1600, found:752.1590.
Example 14: derivatization of indomethacin
Indomethacin, a white-like to yellowish crystalline powder, dissolved in acetone and insoluble in water. Is an artificially synthesized indole derivative. Indomethacin is one of the strongest PG synthetase inhibitors, has remarkable anti-inflammatory and antipyretic effects, and has obvious analgesic effect on inflammatory pain.
The steps of the derivatization of the indometacin in the invention are as follows:
indometacin is firstly derived from imine reaction and then reacts with butadiene and alpha-bromoacetic acid tert-butyl ester:
the experimental procedures and purification were carried out according to the search experiment. RF 0.5(EA: PE 1:2), eluent: petroleum ether/ethyl acetate 20/1, 52% yield, the product was a colorless liquid.
1H NMR(400MHz,CDCl3):δ7.67(d,J＝8.6Hz,2H),7.47(d,J＝8.5Hz,2H), 7.32–7.27(m,3H),7.05(d,J＝2.5Hz,3H),7.01(d,J＝8.5Hz,1H),6.88(d,J＝ 9.1Hz,1H),6.69(dd,J＝9.0,2.5Hz,1H),6.26(dd,J＝8.9,2.7Hz,2H),5.60(dd,J ＝15.2,6.4Hz,1H),5.38(dt,J＝12.9,7.7Hz,1H),4.65(tdd,J＝10.9,8.2,4.4Hz, 1H),4.26(dt,J＝12.1,4.5Hz,2H),3.89(s,2H),3.83(s,3H),2.55–2.48(m,1H), 2.45(s,2H),2.35(d,J＝3.1Hz,4H),1.93–1.79(m,2H),1.70–1.64(m,2H),1.50 –1.23(m,3H),1.06–0.92(m,2H),0.88(dd,J＝6.9,2.1Hz,5H),0.84(d,J＝6.5 Hz,2H),0.73(dd,J＝14.3,7.0Hz,3H).13C NMR(101MHz,CDCl3):δ172.51, 169.27,168.28,156.09,149.59,146.68,140.76,139.33,136.19,133.79,132.99, 131.19,130.81,130.47,129.14,127.09,127.07,126.74,126.62,121.50,115.82, 115.00,111.98,111.77,101.17,78.17,77.20,74.25,74.15,56.52,56.44,55.71,46.94, 42.02,41.90,40.99,40.94,34.48,34.17,31.35,31.28,30.56,28.13,26.21,23.35, 22.00,20.75,16.29,16.26,13.40.HRMS-ESI(m/z)[M+H]+calculated for C48H53ClIN2O6,915.2637,found:915.2631。
Example 15: derivatization of probenecid
Probenecid is also called carbosulfan, white crystalline powder, is dissolved in acetone and is not dissolved in water. Is a renal tubule blocking drug, inhibits the reabsorption of urate by renal tubules, promotes the excretion of uric acid, reduces the concentration of uric acid plasma, reduces the deposition of uric acid, promotes the reabsorption of uric acid sediments, and thus plays a role in resisting chronic gout.
The steps of derivatization of propane sulfonic acid in the invention are as follows:
firstly, probenecid reacts with imine to derive a new imine compound, and then reacts with butadiene and alpha-tert-butyl bromoacetate:
1H NMR(400MHz,CDCl3):δ8.30(d,J＝8.5Hz,2H),7.94(d,J＝8.5Hz,2H), 7.38(d,J＝8.5Hz,2H),7.32(d,J＝8.7Hz,2H),7.17(d,J＝8.6Hz,2H),6.29(d,J ＝8.8Hz,2H),5.62(dt,J＝14.8,6.0Hz,1H),5.40(dt,J＝14.8,7.0Hz,1H),4.35– 4.30(m,2H),3.18–3.08(m,4H),2.63–2.38(m,2H),2.34–2.25(m,4H),1.57(dd, J＝15.1,7.3Hz,4H),1.43(s,9H),0.88(t,J＝7.4Hz,6H).13C NMR(101MHz, CDCl3):δ172.30,163.80,149.51,146.71,144.89,141.05,137.58,133.29,132.81, 130.74,127.33,127.15,126.27,121.57,115.81,80.31,78.17,56.54,49.92,41.87, 35.21,28.09,28.07,21.92,11.13.HRMS-ESI(m/z)[M+H]+calculated for C36H46IN2O6S,761.2121,found:761.2111.
Example 16: fluorescence quenching experiments, as shown in fig. 1, 2, 3 and 4.
In FIG. 1, the Stern-Volmer equation: f0/F＝1+Kqτ0[Q]，Kqτ0＝964.65L/mol，τ0＝5100 ns，Kq＝1.89×108L/(mol*s)；
In FIG. 2, the Stern-Volmer equation: f0/F＝1+Kqτ0[Q]，Kqτ0＝107.31L/mol，τ0＝5100 ns，Kq＝2.1×107L/(mol*s)
In FIG. 3, the Stern-Volmer equation: f0/F＝1+Kqτ0[Q]，Kqτ0＝0.85L/mol，τ0＝5100ns， Kq＝1.67×105L/(mol*s)。
FIG. 4 is a graph showing the change of the main species in the fluorescence quenching reaction system.
The emission intensity of all experiments was recorded using an Edinburgh FS920 fluorescence spectrophotometer. All 4CzIPN solutions were excited at 468nm and emission intensities were collected at 500-800 nm. In a typical experiment, 4CzIPN (10)-5M) adding a proper amount of quenching agent into the DCE solution, placing the solution into a quartz test tube with a spiral top of 4.5cm, degassing by nitrogen, and collectingEmission spectrum of the sample. The results show that imine and triethylamine have a faster quenching effect on photoexcited 4 CzIPN.
Based on the above experimental results, the reaction process is presumed to be as follows. Firstly, the reaction is started, and the activated imine is reduced into an N-alpha free radical by single-electron reduction with an excited-state photosensitizer 4CzIPN, meanwhile, an alkyl halide is reduced to generate an alkyl free radical, then, 1, 3-butadiene is immediately added to generate an allyl free radical, and then, the allyl free radical and the N-alpha free radical are subjected to cross coupling to generate a final target product of the homoallylamine.
Claims (8)
1. A homoallylamine compound is characterized in that the structural formula is as follows:
R1selected from hydrogen, C1-C6 primary alkyl, C1-C6 secondary alkyl, C1-C6 tertiary alkyl, cycloalkane or heterocycloalkane;
R2selected from hydrogen, C1-C6 primary alkyl, C1-C6 secondary alkyl, C1-C6 tertiary alkyl, cycloalkane or heterocycloalkane;
R3selected from hydrogen, primary alkyl groups of C1-C6, secondary alkyl groups of C1-C6, tertiary alkyl groups of C1-C6, cycloalkane or heterocycloalkyl radicals;
r4 is selected from hydrogen, C1-C6 primary alkyl, C1-C6 secondary alkyl, C1-C6 tertiary alkyl, cycloalkane or heterocycloalkane;
r5 is selected from hydrogen, C1-C6 primary alkyl, C1-C6 secondary alkyl, C1-C6 tertiary alkyl, cycloalkane or heterocycloalkane;
the substituent in the substituted phenyl is selected from halogen, alkyl, alkoxy, alkoxycarbonyl or amino.
2. The method for synthesizing the homoallylamine compound of claim 1, wherein the synthetic route is as follows:
under the protection of inert gas and illumination at room temperature and in the presence of an organic photosensitizer and an electron donor, halogenated alkane reacts with 1, 3-butadiene derivative and imine in a solvent to obtain the homoallylamine compound.
3. The synthesis of claim 2, wherein the organic photosensitizer is 4 CzIPN.
4. The synthetic method of claim 2 or 3 wherein the electron donor is 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid diethyl ester HE or triethylamine.
5. The method of claim 4, wherein the molar ratio of haloalkane, 1, 3-butadiene derivative, imine, organic photosensitizer, HE is 2.0:2.0:1.0:0.01: 2.0; the molar ratio of the halogenated alkane 1, the 1, 3-butadiene derivative 2, the imine 3, the organic photosensitizer and the triethylamine is 2.0:2.0:1.0:0.01: 4.0.
6. The method of synthesis according to claim 2, 3 or 5, wherein the solvent is 1, 2-Dichloroethane (DCE).
7. The method for synthesizing the homoallylamine compound of any of claims 2 to 6, wherein the method is used for derivatization of natural active substances.
8. The use according to claim 7, wherein the natural active substances comprise lithocholic acid and estrone and the drug molecules comprise indomethacin and probenecid.
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