CN103232462A - Synthetic method of coumarin-pyrrole compound - Google Patents

Synthetic method of coumarin-pyrrole compound Download PDF

Info

Publication number
CN103232462A
CN103232462A CN2013101744993A CN201310174499A CN103232462A CN 103232462 A CN103232462 A CN 103232462A CN 2013101744993 A CN2013101744993 A CN 2013101744993A CN 201310174499 A CN201310174499 A CN 201310174499A CN 103232462 A CN103232462 A CN 103232462A
Authority
CN
China
Prior art keywords
synthetic method
dmso
nmr
mhz
tonka bean
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN2013101744993A
Other languages
Chinese (zh)
Other versions
CN103232462B (en
Inventor
彭艳红
高涛
汪舰
孙绍发
吴鸣虎
郭海滨
朱晓明
黄文平
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hubei University of Science and Technology
Original Assignee
Hubei University of Science and Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hubei University of Science and Technology filed Critical Hubei University of Science and Technology
Priority to CN201310174499.3A priority Critical patent/CN103232462B/en
Publication of CN103232462A publication Critical patent/CN103232462A/en
Application granted granted Critical
Publication of CN103232462B publication Critical patent/CN103232462B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

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

The synthetic method of tonka bean camphor-azoles
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.
Figure 2013101744993100002DEST_PATH_IMAGE002
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):
Figure 2013101744993100002DEST_PATH_IMAGE003
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
Figure 2013101744993100002DEST_PATH_IMAGE004
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
Figure 2013101744993100002DEST_PATH_IMAGE005
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
Figure 2013101744993100002DEST_PATH_IMAGE006
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
Figure 2013101744993100002DEST_PATH_IMAGE007
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
Figure 2013101744993100002DEST_PATH_IMAGE008
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
Figure 2013101744993100002DEST_PATH_IMAGE010
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
Figure 2013101744993100002DEST_PATH_IMAGE012
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
Figure 2013101744993100002DEST_PATH_IMAGE013
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
Figure 2013101744993100002DEST_PATH_IMAGE014
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
Figure 2013101744993100002DEST_PATH_IMAGE015
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
Figure 2013101744993100002DEST_PATH_IMAGE016
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
Figure 2013101744993100002DEST_PATH_IMAGE017
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
Figure 2013101744993100002DEST_PATH_IMAGE018
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
Figure 2013101744993100002DEST_PATH_IMAGE019
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
Figure 2013101744993100002DEST_PATH_IMAGE020
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
Figure 2013101744993100002DEST_PATH_IMAGE021
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
Figure 2013101744993100002DEST_PATH_IMAGE022
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
Figure 2013101744993100002DEST_PATH_IMAGE023
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
Figure 2013101744993100002DEST_PATH_IMAGE026
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
Figure 2013101744993100002DEST_PATH_IMAGE027
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
Figure 2013101744993100002DEST_PATH_IMAGE028
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
Figure 2013101744993100002DEST_PATH_IMAGE029
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
Figure 2013101744993100002DEST_PATH_IMAGE030
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
Figure 2013101744993100002DEST_PATH_IMAGE034
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
Figure 2013101744993100002DEST_PATH_IMAGE035
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):
Figure 2013101744993100001DEST_PATH_IMAGE001
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.
CN201310174499.3A 2013-05-13 2013-05-13 The synthetic method of coumarin-pyrrole compound Expired - Fee Related CN103232462B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201310174499.3A CN103232462B (en) 2013-05-13 2013-05-13 The synthetic method of coumarin-pyrrole compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201310174499.3A CN103232462B (en) 2013-05-13 2013-05-13 The synthetic method of coumarin-pyrrole compound

Publications (2)

Publication Number Publication Date
CN103232462A true CN103232462A (en) 2013-08-07
CN103232462B CN103232462B (en) 2016-03-02

Family

ID=48880542

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201310174499.3A Expired - Fee Related CN103232462B (en) 2013-05-13 2013-05-13 The synthetic method of coumarin-pyrrole compound

Country Status (1)

Country Link
CN (1) CN103232462B (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CN113072477A (en) * 2021-03-29 2021-07-06 郑州轻工业大学 Method for synthesizing polysubstituted pyrrole derivative

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11365200B2 (en) * 2017-03-22 2022-06-21 Taipei Medical University ATF3 induction compounds

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1371371A (en) * 1999-09-03 2002-09-25 英登纳股份有限公司 Novel derivatives of flavones, xanthones and coumarins
CN1635029A (en) * 2003-12-26 2005-07-06 中国科学院理化技术研究所 Coumarin dye connected by naphthenone and its synthesis and use
WO2009000411A1 (en) * 2007-06-26 2008-12-31 Sanofi-Aventis A transition metal catalyzed synthesis of 2h-indazoles
CN102924459A (en) * 2012-10-25 2013-02-13 华东师范大学 Synthetic method of pyrrole fused-ring 3-indolone type compounds

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1371371A (en) * 1999-09-03 2002-09-25 英登纳股份有限公司 Novel derivatives of flavones, xanthones and coumarins
CN1635029A (en) * 2003-12-26 2005-07-06 中国科学院理化技术研究所 Coumarin dye connected by naphthenone and its synthesis and use
WO2009000411A1 (en) * 2007-06-26 2008-12-31 Sanofi-Aventis A transition metal catalyzed synthesis of 2h-indazoles
CN102924459A (en) * 2012-10-25 2013-02-13 华东师范大学 Synthetic method of pyrrole fused-ring 3-indolone type compounds

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CN103992298B (en) * 2014-06-06 2015-10-28 广西师范大学 The method of synthesis 3-styrylcoumarin compounds
CN103992332B (en) * 2014-06-06 2016-01-13 广西师范大学 Prepare the method for furans [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
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

Also Published As

Publication number Publication date
CN103232462B (en) 2016-03-02

Similar Documents

Publication Publication Date Title
Rios et al. Highly enantioselective synthesis of 2H-1-benzothiopyrans by a catalytic domino reaction
CN103232462A (en) Synthetic method of coumarin-pyrrole compound
Ren et al. Rhodium (III)-catalyzed [4+ 2] annulation of N-arylbenzamidines with 1, 4, 2-dioxazol-5-ones: Easy access to 4-aminoquinazolines via highly selective CH bond activation
Yan et al. Facile access to benzothiophenes through metal-free iodine-catalyzed intermolecular cyclization of thiophenols and alkynes
Li et al. Organocatalytic asymmetric intramolecular [3+ 2] cycloaddition: A straightforward approach to access multiply substituted hexahydrochromeno [4, 3-b] pyrrolidine derivatives in high optical purity
Shi et al. Concise and divergent total synthesis of swainsonine, 7-alkyl swainsonines, and 2, 8a-diepilentiginosine via a chiral heterocyclic enaminoester intermediate
CN111116677A (en) Preparation method and application of metal-organic framework structure compound with chiral pore structure
CN102153488B (en) Alpha,beta-diamino acid derivative, synthetic method thereof and application thereof
Wang et al. Photocatalyzed facile synthesis of 2, 5-diaryl 1, 3, 4-oxadiazoles with polyaniline-g-C3N4-TiO2 composite under visible light
Shang et al. New route synthesis of indolizines via 1, 3-dipolar cycloaddition of pyridiniums and alkynes
Arumugam et al. A facile ionic liquid-accelerated, four-component cascade reaction protocol for the regioselective synthesis of biologically interesting ferrocene engrafted spiropyrrolidine hybrid heterocycles
Zhao et al. Application of the photocyclization reaction of 1, 2-cyclopenta-fused pyridinium perchlorate to formal total syntheses of (−)-cephalotaxine
CN102766092A (en) Method for synthesizing optically active tetrahydroquinoline derivative in presence of chiral spiro phosphoric acid serving as catalyst
Tang et al. Convenient and efficient access to tri-and tetra-substituted 4-fluoropyridines via a [3+ 2]/[2+ 1] cyclization reaction
Magham et al. Enantioselective Desymmetrization Triggered by Iminium‐Enamine Activation: Access to Complex Cyclohepta [b] indoles
Das et al. Total synthesis of racemic and (R) and (S)-4-methoxyalkanoic acids and their antifungal activity
Amiri-Attou et al. Original and rapid access to new alkaloid analogues of neocryptolepine: Synthesis of substituted 6-methyl-6H-indolo [2, 3-b] quinolines via TDAE strategy
CN114874139B (en) Synthesis method of 1-benzyl or allyl 3, 4-dihydroisoquinoline
Ma et al. Copper (I)-catalysed aerobic oxidative selective cleavage of CC bond with DMAP: Facile access to N-substituted benzamides
Sun et al. Iron‐Catalyzed [4C+ 1N] Cyclization of 4‐Acetylenic Ketones with Primary Amines: Synthesis of 5‐(Aryl) alkylidene‐4, 5‐dihydropyrroles
Hu et al. A one-pot synthesis of bisarylhydrazones by Cu (I)-catalyzed aerobic oxidation
Chen et al. Efficient capture of difluorocarbene by pyridinium 1, 4-zwitterionic thiolates: A concise synthesis of difluoromethylene-containing 1, 4-thiazine derivatives
Liu et al. A novel C–C radical–radical coupling reaction promoted by visible light: Facile synthesis of 6-substituted N-methyl 5, 6-dihydrobenzophenanthridine alkaloids
CN112745257B (en) (1R) -phenylamino- (2S) -2-aryl-2-nitrogen heteroaryl cyclopentane and preparation method and application thereof
CN109265403B (en) Synthesis method of benzimidazole and derivatives thereof

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20160302

Termination date: 20180513