CN103232462A - Synthetic method of coumarin-pyrrole compound - Google Patents
Synthetic method of coumarin-pyrrole compound Download PDFInfo
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Abstract
The invention discloses a synthetic method of a coumarin-pyrrole compound. The synthetic method comprises the following step of: in a reactive solvent, with 4-amino coumarin compounds and disubstituted acetylene compounds as raw materials, under the catalysis of palladium (II) and action of an oxidant, carrying out a reaction to obtain the coumarin-pyrrole compound. The synthetic method is mild in reaction conditions, simple and convenient in route and high in atom economy and has a favorable industrial application prospect; and raw materials are low in cost and easy to obtain.
Description
Technical field
The invention belongs to organic compound process application technical field, be specifically related to a kind of tonka bean camphor-azoles synthetic method.
Background technology
Because nitrogen heterocyclic is prevalent in natural product and the medicine, is people's priority fields of studies.As everyone knows, the pyrroles is Five-membered Heterocyclic Compounds, and many drug molecules comprise this type of skeleton, therefore is used as basic structural unit in pharmaceutical chemistry, suc as formula A, be called the blood lipid-lowering medicine atorvastatin (Atorvastatin) of Lipitor by the trade name of Pfizer's sale
1, the different cancer cells of many kinds is had cytotoxicity and the mankind's topoisomerase I 60 is had the Lamellarin D (Lamellarin D) of strongly inhibited effect
2, have NSAID (non-steroidal anti-inflammatory drug) (NSAID) zomepirac (Zomepirac) of antipyretic effect
3With potential cancer therapy drug
4
The several drug molecules that contain the pyrrole structure unit of formula A.
Many synthetic pyrroles' method is reported.Traditional method has Knorr, Paal-Knorr and Hantzsch reaction.Although these methods can effectively be synthesized pyrrole derivative, still there are many obvious defects in the reaction of these classics, and is low as the utilization ratio of starting raw material, reactions steps is many, severe reaction conditions etc., and these have all limited the use range of above method.Except traditional method, the synthetic of pyrrole derivative mainly is to use transition metal-catalyzed cycloaddition reaction now, as shown in the formula B(a) shown in, utilize the active C of Rh (III) or Ru (III) catalyzed oxidation coupling aromatic ring-the orienting group (DG) on the H key and the basic pyrrole derivative of the different replacements of alkynes generation.Though the introducing of orienting group has obtained huge progress, need through polystep reaction the synthetic one-step synthesis B(b that is more prone to avoid using orienting group of azole compounds).
The present invention has realized Pd(II) catalyzed oxidation cycloaddition " lock "-auxiliary trans-enamine and one step of alkynes structure tonka bean camphor-azoles, synthetic method route of the present invention is easy, reaction conditions is gentle, atom economy type height, usefulness are superior, obtain the breakthrough of this system chemosynthesis, and promoted the profound level expansion of this system related drugs chemical research.
Formula B. utilizes active C-and the H key prepares pyrroles's synthetic schemes.A) orienting group (DG) secondary path; B) " lock " secondary path (omnidirectional substituting group).
Summary of the invention
The object of the present invention is to provide a kind of synthetic method of tonka bean camphor-azoles, in reaction solvent, be raw material with 4-aminocoumarin compounds and two replaced acetylene compounds, under palladium (II) catalysis, oxygenant effect, reaction obtains tonka bean camphor-azoles.Reaction process is suc as formula shown in (I):
Formula (I)
Wherein, R
1Be hydrogen atom, alkyl, methoxyl group, aryl or halogen; R
2, R
3Be alkyl, ester group, aryl, benzene, company's benzene or heterocycle.Among the present invention, R
1, R
2, R
3Include but are not limited to above-mentioned group.
Among the present invention, in reaction flask, with 4-aminocoumarin compounds 1(X mmol), two replaced acetylene compounds 2(Y mmol), metallic palladium (U mmol) and oxygenant (V mmol) be dissolved in DMSO(Z mL) in, at r.t., reaction is W hour under the oxygen atmosphere foxing spare, TLC detects, and after reaction finished, rapid column chromatography got product 3(tonka bean camphor-azoles).
In the synthetic method of tonka bean camphor-azoles of the present invention, described metallic palladium is Pd (OAc)
2
Wherein, described metallic palladium consumption is 0.1 equivalent of 4-aminocoumarin compounds.
Wherein, described oxygenant is AgOAc, CuCl
2, Cu (OAc)
2, 1,4-benzoquinones, DDQ, oxygen or ozone.
Wherein, described oxygenant consumption is for being 0.2 equivalent of 4-aminocoumarin compounds.
Wherein, described reaction solvent is any one or arbitrary combination of N,N-dimethylacetamide, methyl-2-pyrrolidone, acetonitrile, methyl-sulphoxide.
Wherein, described 4-aminocoumarin compounds concentration is 0.1 mmol/L, and described pair of replaced acetylene compounds concentration is 0.3 mmol/L.
Wherein, described pair of replaced acetylene compounds equivalents is 3 equivalents.
Wherein, describedly be reflected at 25-120
oCarry out under the C temperature.
Advantage of the present invention comprises: employed each raw material is simple and easy in the synthetic method of the present invention, is the industrialization commodity, and wide material sources are cheap, and stable in properties, and preservation condition is not harsh; Secondly, this synthetic method is simple, processing ease, product yield height, and practicality is especially remarkable; In addition, the present invention has the characteristic that cost is low, efficient is high, technology is simple, pollution is few, has obtained the breakthrough of this system chemosynthesis, and promotes the profound level expansion of this system related drugs chemical research.
Tonka bean camphor-azoles that the present invention makes up has good biological activity, core skeleton for the high amount of drug bioactive molecule, as: blood lipid-lowering medicine atorvastatin (Atorvastatin) with the different cancer cells of many kinds is had Cytotoxic Lamellarin D (Lamellarin D) etc., simultaneously, this structure also is very important a kind of structure design unit, pharmaceutical chemistry field.This compounds biological activity is good, and using value is higher, and the present invention provides practical, novel method efficiently for the high flux screening of medicament research and development, small-molecule drug and complicated natural product complete synthesis.
Embodiment
In conjunction with following specific embodiment, the present invention is described in further detail, and protection content of the present invention is not limited to following examples.Under the spirit and scope that do not deviate from inventive concept, variation and advantage that those skilled in the art can expect all are included in the present invention, and are protection domain with the appending claims.Implement process of the present invention, condition, reagent, experimental technique etc., except the following content of mentioning specially, be universal knowledege and the common practise of this area, the present invention is not particularly limited content.The given data of following examples comprise concrete operations and reaction conditions and product.Product purity is identified by nuclear-magnetism.
Embodiment 1
With coumarin kind compound
1a(0.2 mmol), two replaced acetylene compounds
2a(0.6 mmol), palladium (0.02 mmol) and neutralized verdigris (0.04 mmol) join among the DMSO (2 mL).This reaction mixture stirred 72 hours under the oxygen atmosphere at normal temperature and pressure.After the TLC monitoring reaction finished, underpressure distillation was removed organic solvent and is got crude product, and rapid column chromatography (ethyl acetate: normal hexane=1:4) must product
3aa(90%).
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.80 (s, 1H), 8.37 – 8.17 (m, 1H), 7.56 – 7.20 (m, 13H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.74,151.61, and 135.78,133.88,133.55,131.49,131.07,129.24,128.82,128.18,128.09,127.14,124.39,122.11,121.09,117.00,113.86,107.29,40.73,40.46,40.18,39.90,39.62,39.35,39.07. HRMS (ESI): calculated value [C
23H
15NO
2+ H]
+338.1176, actual value 338.1177.
Embodiment 2
Operation steps is with embodiment 1, productive rate 89%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.72 (s, 1H), 8.11 (s, 1H), 7.65 – 7.08 (m, 12H), 2.43 (s, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.87,149.80, and 135.82,133.73,133.61,133.49,131.48,131.06,130.09,128.80,128.70,128.13,128.10,127.14,121.91,121.06,116.77,113.52,107.32,40.73,40.46,40.18,39.90,39.62,39.35,39.07,20.99. HRMS (ESI): calculated value [C
24H
17NO
2-H]
-350.1187, actual value 350.1197.
Embodiment 3
Operation steps is with embodiment 1, productive rate 99%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.75 (s, 1H), 8.16 (s, 1H), 7.65 – 6.92 (m, 12H), 2.74 (q,
J=7.6 Hz, 2H), 1.30 (t,
J=7.6 Hz, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 158.01,150.04, and 139.93,136.07,133.85,133.70,131.62,131.17,129.18,128.93,128.85,128.27,128.22,127.25,121.15,120.79,116.91,113.68,107.36,40.73,40.46,40.18,39.90,39.62,39.35,39.07,28.18,15.89. HRMS (ESI): calculated value [C
25H
19NO
2-H]
-364.1343, actual value 364.1346.
Embodiment 4
Operation steps is with embodiment 1, productive rate 92%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.59 (s, 1H), 8.18 (d,
J=8.4 Hz, 1H), 7.51 – 7.08 (m, 10H), 7.18 – 6.78 (m, 2H), 3.85 (s, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 160.59,158.04, and 153.31,136.70,133.80,133.07,131.74,131.16,128.91,128.78,128.18,128.10,127.17,123.22,120.82,112.20,107.18,105.62,101.67,56.12,40.73,40.46,40.18,39.90,39.62,39.35,39.07. HRMS (ESI): calculated value [C
24H
17NO
3-H]
-366.1136, actual value 366.1138.
Embodiment 5
Operation steps is with embodiment 1, productive rate 72%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.76 (s, 1H), 8.07 (dd,
J=9.2,3.0 Hz, 1H), 7.45 (m, 1H), 7.40 – 7.23 (m, 11H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 159.48,157.58, and 148.00,135.03,135.02,134.42,133.45,131.43,131.15,129.00,128.79,128.43,128.24,127.36,121.33,119.06,118.99,116.39,116.19,114.93,114.85,107.99,107.78,107.73,40.73,40.46,40.18,39.90,39.62,39.35,39.07. HRMS (ESI): calculated value [C
23H
14FNO
2-H]
-354.0936, actual value 354.0931.
Embodiment 6
Operation steps is with embodiment 1, productive rate 89%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.81 (s, 1H), 8.54 (d,
J=2.2 Hz, 1H), 7.62 (dd,
J=8.8,2.2 Hz, 1H), 7.45 – 7.22 (m, 11H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.37,150.70, and 134.47,134.46,133.43,131.65,131.37,131.13,128.99,128.69,128.44,128.29,127.42,124.56,121.39,119.38,116.36,115.89,107.87,40.73,40.46,40.18,39.90,39.62,39.35,39.07. HRMS (ESI): calculated value [C
23H
14BrNO
2-H]
-414.0135, actual value 414.0141.
Embodiment 7
Operation steps is with embodiment 1, productive rate 79%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.80 (s, 1H), 8.39 (d,
J=2.3 Hz, 1H), 7.52 – 7.42 (m, 2H), 7.40 – 7.20 (m, 10H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.39,150.27, and 134.56,134.45,133.44,131.37,131.13,128.98,128.83,128.70,128.48,128.43,128.27,127.40,121.60,121.39,119.04,115.38,107.85,40.73,40.46,40.18,39.90,39.62,39.35,39.07. HRMS (ESI): calculated value [C
23H
14ClNO
2-H]
-370.0640, actual value 370.0643.
Embodiment 8
Operation steps is with embodiment 1, productive rate 95%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.69 (s, 1H), 7.84 (d,
J=2.5 Hz, 1H), 7.54 – 7.15 (m, 11H), 7.02 (dd,
J=8.9,2.5 Hz, 1H), 3.85 (s, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 158.01,155.99, and 146.06,135.98,133.94,133.65,131.64,131.18,128.97,128.86,128.31,128.20,127.25,121.20,118.20,116.76,114.24,107.50,104.90,56.15,40.73,40.46,40.18,39.90,39.62,39.35,39.07. HRMS (ESI): calculated value [C
24H
17NO
3-H]
-366.1136, actual value 366.1139.
Embodiment 9
Operation steps is with embodiment 1, productive rate 97%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.83 (s, 1H), 8.26 (d,
J=8.4 Hz, 1H), 7.56 (s, 1H), 7.51 – 7.42 (m, 1H), 7.40 – 7.21 (m, 10H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.31,152.05, and 135.12,134.26,133.45,133.27,131.43,131.13,128.95,128.86,128.38,128.24,127.34,124.73,123.54,121.29,117.16,112.99,107.23,40.73,40.46,40.18,39.90,39.62,39.35,39.07. HRMS (ESI): calculated value [C
23H
14ClNO
2-H]
-370.0640, actual value 370.0628.
Embodiment 10
Operation steps is with embodiment 1, productive rate 60%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.74 (s, 1H), 8.12 (d,
J=7.5 Hz, 1H), 7.60 – 6.85 (m, 12H), 2.42 (s, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.30,149.55, and 135.82,133.48,133.21,131.13,130.67,130.06,128.48,128.43,127.78,127.72,126.75,125.39,123.51,120.57,119.43,113.13,106.76,40.73,40.46,40.18,39.90,39.62,39.35,39.07,15.75. HRMS (ESI): calculated value [C
24H
17NO
2-H]
-350.1187, actual value 350.1181.
Embodiment 11
Operation steps is with embodiment 1, productive rate 96%.
1H NMR (500 MHz,
d 6-DMSO, 373 K): δ 12.66 (s, 1H), 8.05 (s, 1H), 7.65 – 6.85 (m, 11H), 2.33 (s, 6H).
13C NMR (125 MHz,
d 6-DMSO, 373 K): δ 158.11,150.21, and 138.57,136.25,133.81,133.43,132.69,131.67,131.17,128.91,128.76,128.20,128.17,127.22,122.34,121.05,117.57,111.40,106.95,40.73,40.46,40.18,39.90,39.62,39.35,39.07,20.08,19.60. HRMS (ESI): calculated value [C
25H
19NO
2-H]
-364.1343, actual value 364.1342.
Embodiment 12
Operation steps is with embodiment 1, productive rate 98%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.79 (s, 1H), 8.36 (d,
J=8.0 Hz, 1H), 8.32 (d,
J=8.6 Hz, 1H), 7.97 (d,
J=8.0 Hz, 1H), 7.86 (d,
J=8.6 Hz, 1H), 7.65 (t,
J=7.2 Hz, 1H), 7.60 (t,
J=7.1 Hz, 1H), 7.42 – 7.23 (m, 10H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.71,147.25, and 136.84,134.12,133.65,133.36,131.61,131.21,128.99,128.93,128.56,128.30,128.24,127.63,127.28,124.35,123.35,121.76,121.15,119.45,109.19,107.32,40.73,40.46,40.18,39.90,39.62,39.35,39.07. HRMS (ESI): calculated value [C
27H
17NO
2-H]
-386.1187, actual value 386.1177.
Embodiment 13
Operation steps is with embodiment 1, productive rate 60%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 8.08 (d,
J=8.0 Hz, 1H), 7.60 – 7.36 (m, 6H), 7.32-7.26 (m, 2H), 7.24 – 7.11 (m, 5H), 4.25 (s, 2H), 2.16 – 1.70 (m, 1H), 0.67 (d,
J=5.9 Hz, 6H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.52,151.79, and 139.07,133.87,133.35,132.32,131.31,130.78,129.15,129.09,128.91,127.61,126.86,124.81,122.74,122.34,117.90,114.33,107.67,53.05,40.51,40.34,40.17,40.01,39.84,39.67,39.51,29.23,19.82. HRMS (EI): calculated value [C
27H
23NO
2]
+393.1729, actual value 393.1727.
Embodiment 14
Operation steps is with embodiment 1, productive rate 85%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 11.68 (s, 1H), 7.73 – 6.72 (m, 10H), 2.76 (s, 2H), 2.24 (s, 2H), 1.10 (s, 6H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 192.43,143.53, and 135.62,132.58,131.01,129.38,128.73,127.92,127.71,127.02,126.53,119.61,117.30,53.38,40.51,40.34,40.17,40.01,39.84,39.67,39.51,36.70,35.34,28.66. HRMS (ESI): calculated value [C
22H
21NO+ H]
+316.1696, actual value 316.1694.
Embodiment 15
Operation steps is with embodiment 1, productive rate 85%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 11.73 (s, 1H), 7.21 (m, 10H), 2.87 (t,
J=5.8,2H), 2.33 (t,
J=6.0,2H), 2.12 – 2.03 (m, 2H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 192.97,144.74, and 135.77,132.56,130.99,129.17,128.73,127.92,127.71,127.04,126.52,119.78,118.53,40.51,40.34,40.17,40.01,39.84,39.67,39.51,39.29,23.82,22.98. HRMS (ESI): calculated value [C
20H
17NO+ H]
+288.1388, actual value 288.1388.
Embodiment 16
Operation steps is with embodiment 1, productive rate 94%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.68 (s, 1H), 8.26 (d,
J=7.6,1H), 7.51 – 7.45 (m, 1H), 7.44 – 7.34 (m, 2H), 7.29 – 7.23 (m, 2H), 7.22 – 7.16 (m, 4H), 7.15 – 7.10 (m, 2H), 2.32 (s, 3H), 2.30 (s, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.86,151.67, and 137.67,136.23,135.64,133.92,131.02,130.73,129.51,129.24,128.85,128.81,128.75,124.47,122.17,120.79,117.09,114.03,107.40,40.76,40.48,40.20,39.93,39.65,39.37,39.09,21.30,21.24. HRMS (ESI): calculated value [C
25H
19NO
2-H]
-364.1343, actual value 364.1348.
Embodiment 17
Operation steps is with embodiment 1, productive rate 95%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.63 (s, 1H), 8.25 (d,
J=7.6 Hz, 1H), 7.41 (m, 3H), 7.29 (d,
J=8.6 Hz, 2H), 7.21 (d,
J=8.5 Hz, 2H), 6.94 (d,
J=8.6 Hz, 2H), 6.88 (d,
J=8.5 Hz, 2H), 3.77 (s, 3H), 3.76 (s, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 159.32,158.57, and 157.94,151.62,135.36,133.70,132.26,130.18,129.10,125.88,124.44,124.08,122.09,120.05,117.07,114.45,114.07,113.72,107.37,55.65,55.44,40.76,40.48,40.20,39.93,39.65,39.37,39.09. HRMS (ESI): calculated value [C
25H
19NO
4-H]
-396.1241, actual value 396.1249.
Embodiment 18
Operation steps is with embodiment 1, productive rate 86%.
1H NMR (500 MHz,
d 6-DMSO, 373 K): δ 12.58 (s, 1H), 8.26 (d,
J=7.2 Hz, 1H), 7.66 – 7.12 (m, 11H).
13C NMR (125 MHz,
d 6-DMSO, 373 K): δ 157.69,152.07, and 136.33,133.36,133.09,132.86,132.59,132.40,130.63,130.43,129.46,129.00,128.27,124.37,122.28,120.61,117.11,114.02,107.76,40.76,40.48,40.20,39.93,39.65,39.37,39.09. HRMS (ESI): calculated value [C
23H
13Cl
2NO
2-H]
-404.0251, actual value 404.0256.
Embodiment 19
Operation steps is with embodiment 1, productive rate 80%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.75 (s, 1H), 8.29 (d,
J=7.4 Hz, 1H), 7.81 – 7.49 (m, 9H), 7.47 – 7.33 (m, 2H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.62,152.19, and 137.93,136.94,135.45,133.07,131.89,129.74,129.62,129.17,128.91,128.50,128.25,125.99,125.82,125.79,125.76,125.67,125.08,125.05,125.02,124.99,124.45,123.82,123.51,122.41,121.28,117.18,113.91,107.92,40.76,40.48,40.20,39.93,39.65,39.37,39.09. HRMS (ESI): calculated value [C
25H
13F
6NO
2-H]
-472.0778, actual value 472.0793.
Embodiment 20
Operation steps is with embodiment 1, productive rate 84%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.82 (s, 1H), 8.16 (d,
J=7.6 Hz, 1H), 7.54 – 7.32 (m, 3H), 7.32 – 7.07 (m, 6H), 7.05 – 6.95 (m, 2H), 2.12 (s, 6H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.84,151.66, and 137.66,137.58,135.26,134.08,133.53,131.61,131.58,131.42,130.47,129.74,129.11,128.97,127.35,125.94,125.27,124.44,121.76,121.04,117.06,114.10,107.56,40.76,40.48,40.20,39.93,39.65,39.37,39.09,20.07,20.03. HRMS (ESI): calculated value [C
25H
19NO
2-H]
-364.1343, actual value 364.1348.
Embodiment 21
Operation steps is with embodiment 1, productive rate 90%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.74 (s, 1H), 8.29 (d,
J=7.7 Hz, 1H), 7.50 – 7.47 (m, 1H), 7.45 – 7.35 (m, 2H), 7.28 (s, 1H), 7.24 – 7.17 (m, 2H), 7.17 – 7.10 (m, 3H), 7.09 – 7.02 (m, 2H), 2.29 (s, 3H), 2.27 (s, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.82,151.71, and 138.03,137.01,135.74,133.97,133.65,131.75,131.54,129.30,128.87,128.71,128.26,128.04,127.91,126.05,124.47,122.22,121.26,117.10,114.00,107.43,40.76,40.48,40.20,39.93,39.65,39.37,39.09,21.52. HRMS (ESI): calculated value [C
25H
19NO
2-H]
-364.1343, actual value 364.1349.
Embodiment 22
Operation steps is with embodiment 1, productive rate 93%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.65 (s, 1H), 8.29 (dd,
J=7.6,1.1 Hz, 1H), 7.50 – 7.44 (m, 1H), 7.44 – 7.34 (m, 2H), 6.99 (s, 2H), 6.96 – 6.93 (m, 2H), 6.91 (s, 2H), 2.23 (s, 6H), 2.20 (s, 6H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.78,151.72, and 137.69,136.76,135.58,133.95,133.61,131.47,129.60,129.25,128.89,128.65,126.48,124.43,122.22,121.34,117.09,114.03,107.47,40.76,40.48,40.20,39.93,39.65,39.37,39.09,21.39. HRMS (ESI): calculated value [C
27H
23NO
2-H]
-392.1656, actual value 392.1669.
Embodiment 23
Operation steps is with embodiment 1, productive rate 62%.
1H NMR (500 MHz,
d 6-DMSO, 373 K): δ 12.91 (s, 1H), 8.27 (d,
J=7.7 Hz, 1H), 7.96 – 7.78 (m, 5H), 7.73 (m, 1H), 7.59 – 7.25 (m, 11H).
13C NMR (125 MHz,
d 6-DMSO, 373 K): δ 157.61,152.26, and 135.95,134.15,133.70,133.57,133.52,132.87,132.09,129.79,129.59,129.21,128.87,128.50,128.21,127.69,126.85,126.56,126.42,126.12,125.91,125.73,125.40,125.26,124.38,122.17,121.10,117.16,114.55,108.96,40.76,40.48,40.20,39.93,39.65,39.37,39.09. HRMS (ESI): calculated value [C
31H
19NO
2-H]
-436.1343, actual value 436.1356.
Embodiment 24
Operation steps is with embodiment 1, productive rate 60%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.91 (s, 1H), 8.25 (d,
J=7.6 Hz, 1H), 7.61 (d,
J=5.1 Hz, 1H), 7.57 (d,
J=5.1 Hz, 1H), 7.53 – 7.45 (m, 2H), 7.44 – 7.35 (m, 2H), 7.21 – 7.16 (m, 1H), 7.16 – 7.07 (m, 2H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.36,151.91, and 136.05,133.45,132.25,129.89,129.73,128.06,127.66,127.58,127.48,124.62,122.35,117.21,113.65,113.60,108.25,40.76,40.48,40.20,39.93,39.65,39.37,39.09. HRMS (ESI): calculated value [C
19H
11NO
2S
2-H]
-348.0158, actual value 348.0158.
Embodiment 25
Operation steps is with embodiment 1, productive rate 63%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.07 (s, 1H), 7.99 (d,
J=7.3 Hz, 1H), 7.43 – 7.29 (m, 3H), 2.68 (qd,
J=7.4,4.7 Hz, 4H), 1.24 (t,
J=7.6 Hz, 3H), 1.14 (t,
J=7.4 Hz, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 158.61,151.43, and 135.80,134.04,128.36,124.33,121.27,120.53,117.08,114.39,106.79,40.76,40.48,40.20,39.93,39.65,39.37,39.09,18.74,17.57,16.75,15.40. HRMS (ESI): calculated value [C
15H
15NO
2-H]
-240.1030, actual value 240.1038.
Embodiment 26
Operation steps is with embodiment 1, productive rate 88%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.78 (m, 1H), 8.27 (m, 1H), 7.70 – 6.90 (m, 12H), 0.26 (m, 9H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.86,157.82, and 151.72,151.69,139.95,138.19,135.99,135.94,134.15,134.08,133.90,133.70,133.00,132.04,131.64,131.15,130.51,129.38,129.12,128.97,128.38,128.25,128.06,127.30,124.51,122.23,122.20,121.36,121.04,117.11,113.93,107.51,107.26,40.76,40.48,40.20,39.93,39.65,39.37,39.09 ,-0.56 ,-0.74. HRMS (ESI): calculated value [C
26H
23NO
2Si-H]
-408.1425, actual value 408.1428.
Embodiment 27
Operation steps is with embodiment 1, productive rate 92%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.72 (s, 1H), 8.35 – 8.13 (m, 1H), 7.57 – 7.09 (m, 10H), 7.02 – 6.80 (m, 2H), 3.77 (m, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 159.39,158.66, and 157.92,157.88,151.70,151.63,135.74,135.53,134.04,133.83,133.66,132.25,131.76,131.19,130.26,129.30,129.20,128.96,128.86,128.19,127.14,125.66,124.50,123.88,122.19,122.13,120.96,120.28,117.11,114.44,114.02,113.74,107.44,107.30,55.65,55.45,40.76,40.48,40.20,39.93,39.65,39.37,39.09. HRMS (ESI): calculated value [C
24H
17NO
3-H]
-366.1136, actual value 366.1144.
Embodiment 28
Operation steps is with embodiment 1, productive rate 81%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.82 (s, 1H), 8.25 (m, 1H), 7.60 – 7.08 (m, 12H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 163.10,162.74, and 161.15,160.80,157.92,157.82,151.71,135.90,135.89,134.12,133.47,133.11,133.05,133.03,131.42,131.15,131.10,131.04,129.94,129.92,129.43,129.04,128.96,128.41,128.29,128.09,128.06,127.33,124.57,124.55,122.23,122.18,121.19,120.03,117.16,116.07,115.90,115.21,115.04,113.94,107.40,107.33,40.76,40.48,40.20,39.93,39.65,39.37,39.09. HRMS (ESI): calculated value [C
23H
14FNO
2-H]
-354.0936, actual value 354.0942.
Embodiment 29
Operation steps is with embodiment 1, productive rate 83%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.85 (s, 1H), 8.34 – 8.19 (m, 1H), 7.55 – 7.34 (m, 9H), 7.32 – 7.13 (m, 1H), 7.12 – 7.00 (m, 1H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 157.62,157.61, and 151.86,151.81,136.04,135.81,135.33,134.18,133.28,132.87,131.34,129.53,129.50,129.25,129.02,128.96,128.78,128.35,128.31,127.85,127.50,127.32,127.24,126.95,126.66,124.54,122.31,122.25,121.70,117.16,117.12,113.81,113.79,113.50,107.81,107.64,40.76,40.48,40.20,39.93,39.65,39.37,39.09. HRMS (ESI): calculated value [C
21H
13NO
2S-H]
-342.0594, actual value 342.0588.
Embodiment 30
Operation steps is with embodiment 1, productive rate 85%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.74 (s, 1H), 8.25 (m, 1H), 7.55 – 7.12 (m, 9H), 6.94 (m, 2H), 3.78 (m, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 163.04,162.66, and 161.08,160.73,159.47,158.71,157.94,157.88,151.72,151.64,135.74,135.54,134.17,133.11,133.05,132.70,132.24,131.01,130.95,130.28,130.14,130.12,129.33,129.25,128.26,128.24,125.49,124.51,123.71,122.14,120.97,119.14,117.12,116.06,115.89,115.18,115.01,114.54,113.99,113.82,107.39,107.32,55.67,55.46,40.76,40.48,40.20,39.93,39.65,39.37,39.09. HRMS (ESI): calculated value [C
24H
16FNO
3-H]
-384.1041, actual value 384.1049.
Embodiment 31
Operation steps is with embodiment 1, productive rate 70%.
1H NMR (500 MHz,
d 6-DMSO, 298 K): δ 12.48 (s, 1H), 8.19 (d,
J=7.0 Hz, 1H), 7.69 – 7.60 (m, 2H), 7.59 – 7.49 (m, 2H), 7.48 – 7.27 (m, 4H), 2.47 (s, 3H).
13C NMR (125 MHz,
d 6-DMSO, 298 K): δ 158.89,151.65, and 135.07,133.35,131.81,130.60,129.10,128.90,128.15,127.89,124.38,121.94,117.09,115.78,114.12,108.49,40.76,40.48,40.20,39.93,39.65,39.37,39.09,10.92. HRMS (ESI): calculated value [C
18H
13NO
2-H]
-274.0874, actual value 274.0872.
Embodiment 32
Operation steps is with embodiment 1, productive rate 40%.
1H NMR (300 MHz,
d 6-DMSO, 298 K): δ 13.38 (s, 1H), 8.51 (dd,
J=7.8,1.2 Hz, 1H), 7.63 – 7.49 (m, 1H), 7.48 – 7.24 (m, 7H), 4.15 (q,
J=7.1 Hz, 2H), 1.06 (t,
J=7.1 Hz, 3H).
13C NMR (75 MHz,
d 6-DMSO, 298 K): δ 160.61,157.22, and 152.33,137.32,132.48,130.97,130.91,130.69,127.65,127.23,124.60,123.43,123.39,117.18,113.29,107.76,60.79,40.76,40.48,40.20,39.93,39.65,39.37,39.09,14.09. HRMS (ESI): calculated value [C
20H
15NO
2-H]
-332.0928, actual value 332.0928.
Claims (9)
1. the synthetic method of a tonka bean camphor-azoles, it is characterized in that, in reaction solvent, be raw material with 4-aminocoumarin compounds and two replaced acetylene compounds, under palladium (II) catalysis, oxygenant effect, reaction obtains tonka bean camphor-azoles, and reaction process is suc as formula shown in (I):
Formula (I)
Wherein, R
1Be hydrogen atom, alkyl, methoxyl group, aryl or halogen; R
2, R
3Be alkyl, ester group, aryl, benzene, company's benzene or heterocycle; Among the present invention, R
1, R
2, R
3Include but are not limited to above-mentioned group.
2. the synthetic method of tonka bean camphor-azoles according to claim 1 is characterized in that described metallic palladium is Pd (OAc)
2
3. the synthetic method of tonka bean camphor-azoles as claimed in claim 1 or 2 is characterized in that described metallic palladium consumption is 0.1 equivalent of 4-aminocoumarin compounds.
4. the synthetic method of tonka bean camphor-azoles according to claim 1 is characterized in that described oxygenant is AgOAc, CuCl
2, Cu (OAc)
2, 1,4-benzoquinones, DDQ, oxygen or ozone.
5. as the synthetic method of tonka bean camphor-azoles as described in claim 1 or 4, it is characterized in that described oxygenant consumption is 0.2 equivalent of 4-aminocoumarin compounds.
6. the synthetic method of tonka bean camphor-azoles according to claim 1 is characterized in that, described reaction solvent is any one or arbitrary combination of N,N-dimethylacetamide, methyl-2-pyrrolidone, acetonitrile, methyl-sulphoxide.
7. the synthetic method of tonka bean camphor-azoles according to claim 1 is characterized in that described 4-aminocoumarin compounds concentration is 0.1 mmol/L, and described pair of replaced acetylene compounds concentration is 0.3 mmol/L.
8. the synthetic method of tonka bean camphor-azoles according to claim 1 is characterized in that described pair of replaced acetylene compounds equivalents is 3 equivalents.
9. the synthetic method of tonka bean camphor-azoles according to claim 1 is characterized in that, describedly is reflected at 25-120
oCarry out under the C temperature.
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CN103992298A (en) * | 2014-06-06 | 2014-08-20 | 广西师范大学 | Method for synthesizing 3-styryl coumarin compounds |
CN103992332A (en) * | 2014-06-06 | 2014-08-20 | 广西师范大学 | Method for preparing furan [3,2-C] coumarin compound |
CN104387405A (en) * | 2014-12-11 | 2015-03-04 | 长沙理工大学 | Method for synthesizing furo [3,2-c ] coumarin derivative |
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CN104387405A (en) * | 2014-12-11 | 2015-03-04 | 长沙理工大学 | Method for synthesizing furo [3,2-c ] coumarin derivative |
CN113072477A (en) * | 2021-03-29 | 2021-07-06 | 郑州轻工业大学 | Method for synthesizing polysubstituted pyrrole derivative |
CN113072477B (en) * | 2021-03-29 | 2022-07-22 | 郑州轻工业大学 | Method for synthesizing polysubstituted pyrrole derivative |
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