CN102659512A - Method for preparing halogenated benzo [alfa] fluorenol - Google Patents
Method for preparing halogenated benzo [alfa] fluorenol Download PDFInfo
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Abstract
The invention provides a method for preparing halogenated benzo [alfa] fluorenol. The method comprises the following step of performing series electrophilic cyclization reaction on 3-aryl-1-(2-(2-aryl ethinyl) phenyl) propargyl-2-alcohol serving as a reaction substrate and various electrophilic reagents such as halogenated succinimide (NXS, X=I, Br and Cl) or simple substance iodine (I2), simple substance bromine (Br2) or iodine chloride (ICl) at the temperature of 0 and 15 DEG C for 10 and 15 hours under the catalysis of AgOTf, and is a 'one-pot method' for efficiently preparing the Halogenated benzo [alfa] fluorenol. The method has the advantages of mild reaction conditions, low cost, less side reaction, high product purity, is easy to operate and can be applied to mass production of the halogenated benzo [alfa] fluorenol; and moreover, separation and purification can be conveniently realized.
Description
Technical field
The invention belongs to technical field of organic chemistry, be specifically related to the preparation method of a kind of halo benzo [a] fluorenol.
Background technology
Have the compound of fluorenes and ring structure owing to contain bigger pi-conjugated system, thereby often have very good photoelectric functional characteristic ((a) Shimizu, A.; Tobe, Y.Angew.Chem.Int.Ed.2011,50,6906. (b) Liu, T.; Xing, C.; Hu, Q.Angew.Chem.Int.Ed.2010,49,2909. (c) Allard, S.; Forster, M.; Souharce, B.; Thiem, H.; Scherf, U.Angew.Chem.Int.Ed.2008,47,4070.), and be widely used as the photoelectric functional material field.In addition; The poly-ring aromatic compounds that present research also finds to have the benzofluorene structure also is the core texture unit of many natural products or medicine; For example from the streptomyces strain movement, can extract natural product 5-diazo benzo [b] fluorenes; This material also is one of major ingredient of microbiotic kantlex ((a) Gould, S.J.; Tamayo, N.; Melville, C.R.; Cone, M.C.J.Am.Chem.Soc.1994,116,2207. (b) Mithani, S.; Weeratunga, G.; Taylor, N.J.; Dmitrienko, G.I.J.Am.Chem.Soc.1994,116,2209. (c) Gould, S.J.; Melville, C.R.; Cone, M.C.; Chen, J.; Carney, J.R.J.Org.Chem.1997,62,320.); In addition, have compound benzo [b] Fluorenone benzofluorene and ring structure, still be used as biosynthetic important as precursors (Gould, the S. of microbiotic kinamycin; Melville, C.Bioorganic Med.Chem.Lett.1995,6,51.).
Therefore, the synthetic benzofluorene compounds of some simple effective methods of research and development has crucial scientific meaning and using value.Yet the method for synthetic this compounds of bibliographical information is but very limited, and reaction all exists some limitation, is difficult to scale operation and application.For example; 1999, people such as Sa á reported compound 3-phenyl-1-(2-(2-virtue ethynyl) phenyl) propargyl-2-alcohol have been heated to 170 ℃, made it that hot aromatization of carbochain at high temperature take place; Benzo [b] compound of fluorene class ((a) Rodr í guez, D. have been synthesized; Castedo, L.; Dom í nguez, D.; Sa á, C.Tetrahedron Lett.1999,40,7701. (b) Rodr í guez, D.; Navarro, A.; Castedo, L.; Dom í nguez, D.; Sa á, C.Org.Lett.2000,2,1497. (c) Rodr í guez, D.; Navarro-V á zquez, A.; Castedo, L.; Dom í nguez, D.; Sa á, C.Tetrahedron Lett.2002,43,2717.); 2004; People such as Rodr í guez David have reported aryl ortho position two acetylides have been realized intramolecular [4+2] cycloaddition through the mode that heats aromatization; The molecular skeleton (Rodr í guez, the D. that synthesize benzo [b] compound of fluorene class and benzo [c] compound of fluorene class; Quint á s, D.; Garc í a, A.; Sa á, C; Dom í nguez, D.; Tetrahedron Lett.2004,45,4711.).This several method need be with reaction mass heated to could transforming than higher temperature, and condition is relatively harsher, and reactant functional group is compatible poor, and products therefrom is the mixture of several kinds of isomerss often, is difficult to separation.Recently, opening the people such as grade has reported through transition metal such as gold perchloride and the common catalytic intramolecularly cascade reaction of silver trifluoromethanesulfonate synthetic benzo [a] fluorene derivatives ((a) Liu, L.; Zhang, J.Angew.Chem.Iht.Ed.2009,48,6093.).Can reach 50-73% through this method products therefrom yield, chemo-selective is better, but the requirement of reaction pair substrate functional group is more single-minded unfortunately, has also only reported four routine case study on implementation in the document.
Belong to group all the time at ((a) Chen, Z. aspect transition metal-catalyzed organic cascade reaction based on the inventor; Gao, L.; Ye, S.; Ding, Q.; Wu, J.Chem.Commun.2012,48,3975. (b) Gao, L.; Ye, S.; Ding, Q.; Chen, Z.; Wu, J.Tetrahedron 2012,68,2765. (c) Ye, C.; Chen, Z.; Wang, H.; Wu, J.Tetrahedron 2012,68, doi:10.1016/j.tet.2012.03.081. (d) Chen, Z.; Ye, C.; Gao, L.; Wu, J.Chem.Commun.2011,47,5623. (e) Chen, Z.; Zheng, D.; Wu, J.Org.Lett.2011,13,848. (f) Chen, Z.; Wu, J.Org.Lett.2010,12,4856. (g) Chen, Z.; Yu, X.; Wu, J.Chem.Commun.2010,46,6356. (h) Yu, X.; Chen, Z.; Yang, X.; Wu, J.J.Comb.Chem.2010,12,374. (i) Chen, Z.; Yang, X.; Wu, J.Chem.Commun.2009,3469.) and close electrocyclic reaction aspect ((a) Chen, Z.; Ding, Q.; Yu, X.; Wu, J.Adv.Synth.Catal.2009,351,1692. (b) Chen, Z.; Yu, X.; Su, M.; Wu, J.Adv.Synth.Catal.2009,351,2702. (c) Chen, Z.; Su, M.; Yu, X.; Wu, J.Org.Biomol.Chem.2009,7,4641. (d) Chen, Z.; Pan, X.; Wu, J.Synlett 2011,964. (e) Ding, Q.; Chen, Z.; Yu, X.; Peng, Y.; Wu; J.Tetrahedron Lett.2009; 50,340.) research work of synthetic all kinds of cyclic organic compounds accumulation, we combine these two types of organic chemical reactionses imagination; Develop the novel cascade reaction under one type of transition metal and the electrophilic reagent acting in conjunction, synthesize the benzofluorene compounds.Therefore; The present invention is intended to report one type and utilizes transition metal-catalyzed close electrocyclic reaction; The new technology of high-level efficiency, high chemo-selective ground synthesizing halogen benzo [a] fluorenol verivate under comparatively gentle condition; And the intramolecular halogen atom of product can further transform under the effect of palladium catalyst, thereby on halo benzo [a] fluorenol molecular skeleton, introduces more functional group.
Summary of the invention
The object of the invention is to provide the preparation method of a kind of halo benzo [a] fluorenol; Present method reaction conditions is gentle, easy and simple to handle, cost is lower, side reaction is few, product purity is high, be convenient to separate purification; Can be suitable for fairly large preparation; Products therefrom has good photoelectric functional characteristic and potential biology and pharmaceutical activity, therefore can be applicable to photoelectric functional material and biomedicine field, has extraordinary application prospect is arranged.
The present invention realizes like this; The preparation method of a kind of halo benzo [a] fluorenol, method steps is: adopt 3-aryl-1-(2-(2-virtue ethynyl) phenyl) propargyl-2-alcohol to make itself and various electrophilic reagents such as N-halogenated succinimide imide, iodine, simple substance bromine or iodine chloride under the catalyst condition as reaction substrate; Close electrocyclic reaction through a series connection character; Temperature of reaction is 0-15 ℃, and the reaction times is 10-15 hour, and one kettle way efficiently makes halo benzo [a] fluorenol.
Said 3-aryl-1-(2-(2-virtue ethynyl) phenyl) propargyl-2-alcohol is 1: 1.2 with the ratio of various electrophilic reagents such as N-halogenated succinimide imide, iodine, simple substance bromine or iodine chloride.
The employed organic solvent of reaction system is a methylene dichloride, 1,2-ethylene dichloride or toluene.
React employed catalyzer lewis acid catalyst like silver trifluoromethanesulfonate, copper trifluoromethanesulfcomposite or Bismuth triflate.
Halogen atom in product halo benzo [a] fluorenol of gained can also continue all kinds of linked reactions take place under the effect of palladium catalyst, thereby on the product molecular skeleton, introduces more functional group.
Said N-halogenated succinimide imide is N-iodo succimide, N-bromo-succinimide or N-chlorosuccinimide.
Reaction equation is following:
R wherein
1, R
2, R
3=H or CH
3, OCH
3Etc. various electron-donating groups, and various electron-withdrawing groups such as F, Cl.
Concrete operations are: under the nitrogen protection with electrophilic reagent N-halogenated succinimide imide (halogen atom is: iodine, bromine or chlorine) or iodine, simple substance bromine, iodine chloride (0.36mmol; 1.2equiv) and catalyzer silver trifluoromethanesulfonate (0.015mmol; 0.05equiv) be dissolved in the organic solvent dichloromethane; Under stirring, be added drop-wise to 3-aryl-1-(2-(2-virtue ethynyl) phenyl) propargyl-2-alcohol (0.30mmol at 10 ℃; 1.0equiv) dichloromethane solution in, down continued stirring reaction 10-15 hour in nitrogen protection, detect to complete reaction with TLC in the reaction process.Earlier solvent is revolved during aftertreatment dried, directly go up silica gel column chromatography separate purified product halo benzo [a] fluorenol verivate.Outstanding by the time in the inventive method yield, the chemo-selective of reaction is outstanding, the mild condition, (R wherein applied widely of substrate
1, R
2, R
3=H or CH
3, OCH
3Etc. various electron-donating groups or various electron-withdrawing groups such as F, Cl), easy and simple to handle, cost is lower, side reaction is few, product purity is high, be convenient to separate purification, applicable to fairly large preparation.
In the present invention, the Atom economy of reaction is very high, reactant 3-aryl-1-(2-(2-virtue ethynyl) phenyl) ratio of propargyl-2-alcohol and electrophilic reagent is 1: 1.0～1.2 very well carrying out of ability just, reactant reveals good greenization thus.
Operation of the present invention is easy, and product yield is high, and chemo-selective is outstanding, and the product of gained has the application prospect of extraordinary photoelectric functional material or biological medicine aspect.
Description of drawings
Fig. 1 is the single crystal structure figure of 6-iodo-11-phenyl-11H-benzo [a] fluorenol compound 2a.
Fig. 2 is the corresponding molecular structure of compounds figure of single crystal structure of 6-iodo-11-phenyl-11H-benzo [a] fluorenol compound 2a.
Embodiment
Like Fig. 1, shown in Figure 2, following embodiment further specifies of the present invention, rather than limits scope of the present invention.
Under the nitrogen protection with N-iodo succimide (NIS; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 6-iodo-11-phenyl-11H-benzo [a] fluorenol 2a.Productive rate: 71%;
1H NMR (400MHz, CDCl
3): δ 8.81-8.79 (d, J=8.00Hz, 1H), 8.49 (s, 1H), 7.85-7.83 (d, J=8.00Hz, 1H), 7.74-7.72 (d, J=8.00Hz, 1H), 7.42-7.39 (m, 4H), 7.37-7.32 (m, 2H), 7.28-7.19 (m, 5H), 2.54 (s, 1H);
13C NMR (100MHz, CDCl
3): δ 152.3,147.1, and 142.6,141.8,139.2,137.8,135.1,128.6,128.5,128.4,128.1,127.4,127.2,127.1,126.5,125.2,124.9,124.1,122.5,85.0,83.4; HRMS (EI) calcd for C
23H
15IO (M)
+: 434.0168, found:434.0179.Elemental analysis calcd.For C
23H
15IO:C 63.61, and H 3.48; Found:C 63.49, H 3.59.
Under the nitrogen protection with N-bromo-succinimide (NBS; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 6-bromo-11-phenyl-11H-benzo [a] fluorenol 2b.Productive rate: 54%;
1H NMR (400MHz, CDCl
3): δ 8.59-8.57 (d, J=8.00Hz, 1H), 8.14 (s, 1H), 7.84-7.82 (d, J=8.00Hz, 1H), 7.76-7.74 (d, J=8.00Hz, 1H, 7.39-7.36 (m, 3H), 7.33-7.29 (m, 2H), 7.24-7.18 (m, 4H), 2.56 (s, 1H);
13C NMR (100MHz, CDCl
3): δ 152.2,147.3,142.5,138.6,135.9,134.7,134.0,128.7,128.5,128.4,127.6,127.2,126.9,126.6,125.1,124.9,124.1,123.8,114.7,83.9.HRMS (EI) calcd forC
23H
15BrO (M)
+: 386.0306, found:386.0321,388.0277.
Under the nitrogen protection with N-iodo succimide (NIS; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-phenyl-1-(2-(2-phenylacetylene base-5-fluorine) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 3-fluoro-6-iodo-11-phenyl-11H-benzo [a] fluorenol 2c.Productive rate: 56%;
1H NMR (400MHz, CDCl
3): δ 8.80-8.78 (d, J=8.00Hz, 1H), 8.45 (s, 1H), 7.72-7.69 (m, 1H); 7.51-7.43 (m, 2H), 7.20-7.14 (m, 2H), 7.36-7.34 (m, 1H), 7.29-7.21 (m; 3H), 7.16-7.12 (t, J=8.00Hz, 1H), 2.53 (s, 1H);
13C NMR (100MHz, CDCl
3): δ 167.7,161.9, and 159.5,152.4,146.68,146.61,141.9,141.6; 138.8,138.6,132.2,132.0,130.8,129.9,129.8,129.4; 129.3,128.9,128.8,128.5,128.2,127.3,124.8,124.1; 122.6,117.2,117.0,108.7,108.5,83.86,83.83.
Under the nitrogen protection with N-bromo-succinimide (NBS; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-phenyl-1-(2-(2-phenylacetylene base-5-fluorine) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 3-fluoro-6-bromo-11-phenyl-11H-benzo [a] fluorenol 2d.Productive rate: 54%;
1H NMR (400MHz, CDCl
3): δ 8.56-8.54 (d, J=8.00Hz, 1H), 8.06 (s, 1H), 7.86-7.83 (m, 1H), 7.39-7.32 (m, 4H), 7.10-7.05 (m, 1H);
13C NMR (100MHz, CDCl
3): δ 167.7,162.1, and 159.6,151.8,147.5,142.3,138.4,135.6,135.5; 135.2,133.2133.1,130.8,128.8,128.5,127.9,127.8,127.3,125.1; 124.8,124.0,123.4,117.6,117.3,116.1,110.7,110.5,83.8.
Under the nitrogen protection with N-iodo succimide (NIS; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-(4-methoxyl group) phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 6-iodo-9-methoxyl group-11-phenyl-11H-benzo [a] fluorenol 2e.Productive rate: 62%;
1H NMR (400MHz, CDCl
3): δ 8.65-8.63 (d, J=8.00Hz, 1H), 8.432 (s, 1H), 7.79-7.75 (d, J=8.00Hz; 1H), and 6.68-6.66 (d, J=8.00Hz, 1H), 7.36-7.35 (m, 2H), 7.31-7.27 (m; 1H), 7.21-7.19 (m, 3H), 7.07-7.05 (m, 1H), 6.99 (s, 1H); 6.88-6.83 (m, 2H), 3.879 (s, 1H), 3.71-3.68 (d, J=12.0Hz, 3H);
13C NMR (100MHz, CDCl
3): δ 160.4,154.5,146.2,142.6,141.6,138.1,134.5,131.7,129.9,128.56,128.5,127.4,127.2,127.0,126.0,124.9,124.8,123.4,113.2,110.2,84.8,83.1,55.49.
Under the nitrogen protection with N-bromo-succinimide (NBS; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-(4-methoxyl group) phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 6-bromo-9-methoxyl group-11-phenyl-11H-benzo [a] fluorenol 2f.Productive rate: 59%;
1H NMR (400MHz, CDCl
3): δ 8.45-8.43 (d, J=8.00Hz, 1H), 8.09 (s, 1H), 7.80-7.78 (d, J=8.00Hz, 1H), 7.72-7.70 (d, J=8.00Hz, 1H), 7.38-7.18 (m, 7H), 6.87-6.84 (m, 2H), 3.72 (s, 3H);
13C NMR (100MHz, CDCl
3): δ 160.2,154.3,146.4,142.6,136.1,134.1,133.8,131.1,128.4,128.0,127.6,127.2,126.8,126.1,124.9,124.7,124.5,114.3,113.8,110.1,83.6,55.4.
Under the nitrogen protection with N-iodo succimide (NIS; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-(4-ethyl) phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 6-iodo-9-ethyl-11-phenyl-11H-benzo [a] fluorenol 2g.Productive rate: 50%;
1H NMR (400MHz, CDCl
3): δ 8.69-8.67 (d, J=8.00Hz, 1H), 8.46 (s, 1H), 7.82-7.80 (d, J=8.00Hz; 1H), and 7.71-7.69 (d, J=8.00Hz, 1H), 7.39-7.37 (m, 2H), 7.35-7.29 (m; 2H), 7.25-7.18 (m, 4H), 7.18 (s, 1H), 2.62-2.60 (t, J=8.00Hz; 2H), 2.5 (s, 1H), 1.21-1.17 (t, J=8.00Hz, 3H);
13C NMR (100MHz, CDCl
3): δ 152.6,146.9,145.2,142.8,141.7,138.0,136.8,134.9,128.5,128.4,127.6,127.4,127.1,127.0,126.3,125.04,125.00,123.7,122.3,85.0,83.3,28.8,15.4.
Under the nitrogen protection with N-bromo-succinimide (NBS; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-(4-ethyl) phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 6-bromo-9-ethyl-11-phenyl-11H-benzo [a] fluorenol 2h.Productive rate: 37%;
1H NMR (400MHz, CDCl
3): δ 8.48-8.46 (d, J=8.00Hz, 1H), 8.11 (s, 1H), 7.82-7.79 (d, J=8.00Hz; 1H), and 7.74-7.72 (d, J=8.00Hz, 1H), 7.39-7.33 (m, 3H), 7.30-7.27 (m; 1H), 7.25-7.17 (m, 4H), 7.15 (s, 1H), 2.63-2.59 (t, J=8.00Hz; 2H), 2.53 (s, 1H), 1.21-1.17 (t, J=8.00Hz, 3H);
13C NMR (100MHz, CDCl
3): δ 152.4,147.09,145.1,142.7,136.2,136.1,134.5,133.9,128.4,128.2,128.0,127.6,127.1,126.8,126.4,125.0,123.6,123.4,114.6,83.8.
Under the nitrogen protection with N-iodo succimide (NIS; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-phenyl-1-(2-(2-is to the fluorophenethyl alkynyl) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 6-iodo-11-to fluorophenyl-11H-benzo [a] fluorenol 2i.Productive rate: 46%;
1H NMR (400MHz, CDCl
3): δ 8.81-8.76 (d, J=8.00Hz, 1H), 8.50 (s, 1H), 7.82-7.80 (d, J=8.00Hz, 1H); 7.75-7.73 (d, J=8.00Hz, 1H), 7.45-7.42 (m, 2H), 7.40-7.28 (m, 3H); 7.25 (s, 2H), 6.93-6.89 (t, J=8.00Hz, 1H), 2.56 (s, 1H);
13C NMR (100MHz, CDCl
3): δ 171.2,163.2,160.7,152.1,146.7,142.0,139.0,138.3,137.7,135.1,128.7,128.39,128.31,127.5,127.2,126.7,126.68,126.63,125.0,124.0,122.5,115.4,115.2,84.9.
Under the nitrogen protection with iodine (I
20.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-(4-methoxyl group) phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 6-iodo-9-methoxyl group-11-phenyl-11H-benzo [a] fluorenol 2e.Productive rate: 43%;
1H NMR (400MHz, CDCl
3): δ 8.65-8.63 (d, J=8.00Hz, 1H), 8.432 (s, 1H), 7.79-7.75 (d, J=8.00Hz; 1H), and 6.68-6.66 (d, J=8.00Hz, 1H), 7.36-7.35 (m, 2H), 7.31-7.27 (m; 1H), 7.21-7.19 (m, 3H), 7.07-7.05 (m, 1H), 6.99 (s, 1H); 6.88-6.83 (m, 2H), 3.879 (s, 1H), 3.71-3.68 (d, J=12.0Hz, 3H);
13C NMR (100MHz, CDCl
3): δ 160.4,154.5,146.2,142.6,141.6,138.1,134.5,131.7,129.9,128.56,128.5,127.4,127.2,127.0,126.0,124.9,124.8,123.4,113.2,110.2,84.8,83.1,55.49.
Under the nitrogen protection with iodine chloride (ICl; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 6-iodo-11-phenyl-11H-benzo [a] fluorenol 2a.Productive rate: 45%;
1H NMR (400MHz, CDCl
3): δ 8.81-8.79 (d, J=8.00Hz, 1H), 8.49 (s, 1H), 7.85-7.83 (d, J=8.00Hz, 1H), 7.74-7.72 (d, J=8.00Hz, 1H), 7.42-7.39 (m, 4H), 7.37-7.32 (m, 2H), 7.28-7.19 (m, 5H), 2.54 (s, 1H);
13C NMR (100MHz, CDCl
3): δ 152.3,147.1, and 142.6,141.8,139.2,137.8,135.1,128.6,128.5,128.4,128.1,127.4,127.2,127.1,126.5,125.2,124.9,124.1,122.5,85.0,83.4; HRMS (EI) calcd for C
23H
15IO (M)
+: 434.0168, found:434.0179.Elemental analysis calcd.For C
23H
15IO:C63.61, H 3.48; Found:C 63.49, H 3.59.
Under the nitrogen protection with simple substance bromine (Br2; 0.36mmol) and catalyst A gOTf (0.015mmol) be dissolved in the organic solvent dichloromethane; At 10 ℃ in stirring the dichloromethane solution that is added drop-wise to 3-phenyl-1-(2-(2-phenylacetylene base-5-fluorine) phenyl) propargyl-2-pure (0.30mmol) down; 10 ℃ following stirring reaction 10-15 hour, TLC detects to complete reaction.Reaction finishes, solvent is revolved dried, crude product directly go up silica gel column chromatography separate purified product 3-fluoro-6-bromo-11-phenyl-11H-benzo [a] fluorenol 2d.Productive rate: 51%;
1H NMR (400MHz, CDCl
3): δ 8.56-8.54 (d, J=8.00Hz, 1H), 8.06 (s, 1H), 7.86-7.83 (m, 1H), 7.39-7.32 (m, 4H), 7.10-7.05 (m, 1H) .HRMS (EI) calcd for C
23H
14BrFO (M)
+: 404.0212, found:404.0219,406.0194.
Under the nitrogen protection with 6-iodo-11-phenyl-11H-benzo [a] fluorenol 2a (0.20mmol; 1.0equiv), to methylphenylboronic acid (0.21mmol; 1.05equiv) and catalyzer dichloro two triphenyl phosphorus palladium (0.004mmol; 2mol%) and mineral alkali salt of wormwood (0.40mmol 2.0equiv) is dissolved in mixed organic solvents DMF/H
2O (2.0mL, 5: 1, v/v) in, reaction system is heated to 50 ℃ in stirring reaction down 6 hours, TLC detects to complete reaction.Reaction finishes, and adds entry (10mL) cancellation reaction, the ethyl acetate extraction organism; Organic phase is washed with saturated brine; Anhydrous sodium sulfate drying filters the back and concentrates, and crude product is directly gone up the silica gel column chromatography separation and obtained purified product 6-(4-aminomethyl phenyl)-11-phenyl-11H-benzo [a] fluorenol 3a.Productive rate:＞99%;
1H NMR (400MHz, CDCl
3): δ 7.81-7.79 (d, J=8.00Hz, 1H), 7.75-7.73 (d, J=8.00Hz, 1H), 7.73 (s; 1H), and 7.40-7.38 (m, 3H), 7.24-7.28 (m, 1H), 7.26-6.20 (m, 3H); 7.17-7.10 (m, 3H), 7.06-6.98 (m, 3H), 6.93-6.91 (m, 1H), 6.78-6.77 (d; J=4.00Hz, 1H), 2.47 (s, 1H), 2.41 (s, 1H); HRMS (EI) calcd for C
30H
22O (M)
+: 398.1671, found:398.1677.
Under the nitrogen protection with 6-iodo-11-phenyl-11H-benzo [a] fluorenol 2a (0.20mmol; 1.0equiv), to methylbenzene acetylene (0.22mmol; 1.10equiv) and catalyzer dichloro two triphenyl phosphorus palladiums (0.004mmol, 2mol%), (0.004mmol 2mol%) is dissolved in the organic solvent triethylamine (2.0mL) cuprous iodide; Reaction system is heated to 50 ℃ in stirring reaction down 3-4 hour, and TLC detects to complete reaction.Reaction finishes, and revolves dried solvent, and thick product is directly gone up the silica gel column chromatography separation and obtained purified product 6-(4-methylbenzene ethynyl)-11-phenyl-11H-benzo [a] fluorenol 4a.Productive rate: 83%;
1H NMR (400MHz, CDCl
3): δ 8.59-8.57 (d, J=8.00Hz, 1H), 8.14 (s, 1H), 7.84-7.80 (m, 2H), 7.06-7.58 (d; J=8.00Hz, 2H), 7.42-7.36 (m, 4H), 7.34-7.31 (m, 2H), 7.29-7.23 (m; 4H), 7.21-7.17 (m, 2H), 2.52 (s, 1H), 2.42 (s, 3H);
13C NMR (100MHz, CDCl
3): δ 152.2,145.0, and 142.7,139.1,138.9,136,8,134.9; 133.5,131.5,129.4,128.9,126.4,128.4,128.7,128.47; 128.44,128.2,127.3,127.1,126.1,125.0,124.9,123.9; 122.8,120.2,115.3,93.6,87.8,83.7,21.6.HRMS (EI) calcd forC
32H
22O (M)
+: 422.1671, found:422.1688.
Claims (6)
1. the preparation method of a halo benzo [a] fluorenol is characterized in that method steps is: adopt 3-aryl-1-(2-(2-virtue ethynyl) phenyl) propargyl-2-alcohol as reaction substrate, make itself and N-halogenated succinimide imide (NXS, X=I, Br, Cl) or iodine (I
2), simple substance bromine (Br
2) or iodine chloride various electrophilic reagents such as (ICl) under the catalyst condition, through one the series connection character close electrocyclic reaction, temperature of reaction is 0-15 ℃, the reaction times is 10-15 hour, one kettle way efficiently makes halo benzo [a] fluorenol.
2. the preparation method of halo benzo according to claim 1 [a] fluorenol is characterized in that said 3-aryl-1-(2-(2-virtue ethynyl) phenyl) and propargyl-2-alcohol and N-halogenated succinimide imide (NXS, X=I, Br, Cl), iodine (I
2), simple substance bromine (Br
2) or the ratio of iodine chloride various electrophilic reagents such as (ICl) be 1: 1.2.
3. the preparation method of halo benzo according to claim 1 [a] fluorenol is characterized in that the employed organic solvent of reaction system is a methylene dichloride, 1,2-ethylene dichloride or toluene.
4. the preparation method of halo benzo according to claim 1 [a] fluorenol is characterized in that reacting employed catalyzer lewis acid catalyst like silver trifluoromethanesulfonate, copper trifluoromethanesulfcomposite or Bismuth triflate.
5. the preparation method of the described halo benzo of claim 1 [a] fluorenol; It is characterized in that the halogen atom in product halo benzo [a] fluorenol of gained can also continue linked reaction takes place under the effect of palladium catalyst, thereby on the product molecular skeleton, introduce more functional group.
6. the preparation method of halo benzo according to claim 2 [a] fluorenol; It is characterized in that said N-halogenated succinimide imide (NXS; X=I, Br Cl) is N-iodo succimide (NIS), N-bromo-succinimide (NBS) or N-chlorosuccinimide (NCS).
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| CN103145515A (en) * | 2013-03-14 | 2013-06-12 | 江西师范大学 | Preparation method of 3-halogenated-2-alkynyl-1-ketone naphthalene series compound |
| CN105330522A (en) * | 2015-10-26 | 2016-02-17 | 江西师范大学 | Preparing method for benzo [b] fluorenone series compounds |
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| CN102030701A (en) * | 2010-11-04 | 2011-04-27 | 华东师范大学 | Fluoradene derivative and preparation method thereof |
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| US20060025636A1 (en) * | 2002-08-29 | 2006-02-02 | Hirohumi Shiigi | Process for preparation of spirofluorenols |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145515A (en) * | 2013-03-14 | 2013-06-12 | 江西师范大学 | Preparation method of 3-halogenated-2-alkynyl-1-ketone naphthalene series compound |
| CN103145515B (en) * | 2013-03-14 | 2015-11-25 | 江西师范大学 | A kind of preparation method of 3-halo-2-alkynyl-1-ketone group naphthalene series compound |
| CN105330522A (en) * | 2015-10-26 | 2016-02-17 | 江西师范大学 | Preparing method for benzo [b] fluorenone series compounds |
| CN105330522B (en) * | 2015-10-26 | 2017-08-08 | 江西师范大学 | A kind of preparation method of benzo [b] Fluorenone series compound |
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