CN102659512B - 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 a kind of preparation method of halo benzo [a] fluorenol.
Background technology
There is fluorenes and the compound of ring structure due to containing larger pi-conjugated system, thus often there is 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 photoelectric functional material field.In addition, the poly-ring aromatic compounds that current research also finds to have benzofluorene structure is also the core texture unit of many natural products or medicine, natural product 5-diazo benzo [b] fluorenes such as can be extracted from streptomyces strain movement, this material is also one of major ingredient of antibiotic 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, there is compound benzo [b] Fluorenone of the also ring structure of benzofluorene, or be used as biosynthetic important as precursors (Gould, the S. of antibiotic kinamycin; Melville, C.Bioorganic Med.Chem.Lett.1995,6,51.).
Therefore, some simple effective methods of research and development synthesis benzofluorene compounds has very important scientific meaning and using value.But the method for this compounds of synthesis of bibliographical information is but very limited, and reaction all also exists some limitation, is difficult to scale operation and application.Such as, 1999, the people such as Sa á report and compound 3-phenyl-1-(2-(2-virtue ethynyl) phenyl) propargyl-2-alcohol are heated to 170 DEG C, make it that hot aromatization of carbochain at high temperature occur, benzo [b] compound of fluorene class ((a) Rodr í guez, D. are 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, the people such as Rodr í guez David report and aryl ortho position two acetylide are achieved intramolecular [4+2] cycloaddition by the mode heating aromatization, synthesize molecular skeleton (Rodr í guez, the D. of 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 needs reactant to be heated to higher temperature and could transform, and condition is harsher, and the compatibility of reactant functional group is poor, and products therefrom is often the mixture of several isomers, is difficult to be separated.Recently, open and wait people to report by transition metal as cascade reaction synthesis benzo [a] fluorene derivatives ((a) Liu, L. in the molecule of gold perchloride and silver trifluoromethanesulfonate co-catalysis; Zhang, J.Angew.Chem.Iht.Ed.2009,48,6093.).Can reach 50-73% by the method products therefrom yield, chemo-selective is better, but reaction is more single-minded to the requirement of substrate functional group unfortunately, also only reports four routine case study on implementation in the document.
Based on the present inventor place group ((a) Chen, Z. in transition metal-catalyzed organic cascade reaction all the time; 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.) the research work accumulation of all kinds of cyclic organic compounds is synthesized, this two classes organic chemical reactions combines imagination by we, develop the novel cascade reaction under a class transition metal and electrophilic reagent acting in conjunction, synthesize benzofluorene compounds.Therefore, the present invention is intended to report one class and utilizes transition metal-catalyzed close electrocyclic reaction, the new technology of high-level efficiency, high chemo-selective ground synthesizing halogen benzo [a] fluorenol derivative under comparatively gentle condition, and, halogen atom in product molecule can transform further under the effect of palladium catalyst, thus introduces more functional group on halo benzo [a] fluorenol molecular skeleton.
Summary of the invention
The object of the invention is the preparation method providing a kind of halo benzo [a] fluorenol, present method reaction conditions is gentle, easy and simple to handle, cost compared with low, side reaction is few, product purity is high, be convenient to separating-purifying, fairly large preparation can be suitable for, products therefrom has good photoelectric functional characteristic and potential biological and pharmacoligical activities, therefore can be applicable to photoelectric functional material and biomedicine field, have and have extraordinary application prospect.
The present invention realizes like this, a kind of preparation method of halo benzo [a] fluorenol, method steps is: adopt 3-aryl-1-(2-(2-virtue ethynyl) phenyl) propargyl-2-alcohol as reaction substrate, make the various electrophilic reagents such as itself and N-N-halosuccinimides, iodine, simple substance bromine or iodine chloride under catalyst condition, by the close electrocyclic reaction of a series nature, temperature of reaction is 0-15 DEG C, reaction times is 10-15 hour, efficiently obtained halo benzo [a] fluorenol of one kettle way.
The ratio of described 3-aryl-1-(2-(2-virtue ethynyl) phenyl) the various electrophilic reagent such as propargyl-2-alcohol and N-N-halosuccinimides, iodine, simple substance bromine or iodine chloride is 1: 1.2.
The organic solvent that reaction system uses is methylene dichloride, 1,2-ethylene dichloride or toluene.
To react the catalyzer lewis acid catalyst that uses as silver trifluoromethanesulfonate, copper trifluoromethanesulfcomposite or Bismuth triflate.
Halogen atom in product halo benzo [a] fluorenol of gained can also continue all kinds of linked reaction occurs under the effect of palladium catalyst, thus introduces more functional group on product molecule skeleton.
Described N-N-halosuccinimides is N-N-iodosuccinimide, N-bromo-succinimide or N-chlorosuccinimide.
Reaction equation is as follows:
Wherein R
1, R
2, R
3=H or CH
3, OCH
3etc. various electron-donating group, and the various electron-withdrawing group such as F, Cl.
Concrete operations are: under nitrogen protection, by electrophilic reagent N-N-halosuccinimides, (halogen atom is: iodine, bromine or chlorine) or iodine, simple substance bromine, iodine chloride (0.36mmol, 1.2equiv) with catalyzer silver trifluoromethanesulfonate (0.015mmol, 0.05equiv) be dissolved in organic solvent dichloromethane, under stirring, 3-aryl-1-(2-(2-virtue ethynyl) phenyl) propargyl-2-alcohol (0.30mmol is added drop-wise at 10 DEG C, in dichloromethane solution 1.0equiv), stirring reaction 10-15 hour is continued under nitrogen protection, detect to complete reaction with TLC in reaction process.First solvent is spin-dried for during aftertreatment, product halo benzo [a] the fluorenol derivative that direct upper silica gel column chromatography is separated pure.By the time outstanding in the inventive method yield, the chemo-selective of reaction is outstanding, mild condition, (the wherein R applied widely of substrate
1, R
2, R
3=H or CH
3, OCH
3etc. various electron-donating group or the various electron-withdrawing group such as F, Cl), easy and simple to handle, cost compared with low, side reaction is few, product purity is high, be convenient to separating-purifying, be 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) propargyl-2-alcohol and the ratio of electrophilic reagent be 1: 1.0 ~ 1.2 with regard to very well the carrying out of energy, 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.
Accompanying drawing explanation
Fig. 1 is the single crystal structure figure of the iodo-11-phenyl of 6--11H-benzo [a] fluorenol compound 2a.
Fig. 2 is the molecular structure of compounds figure that the single crystal structure of 6-iodo-11-phenyl-11H-benzo [a] fluorenol compound 2a is corresponding.
Embodiment
As shown in Figure 1 and Figure 2, the following examples further illustrate of the present invention, instead of limit the scope of the invention.
Example 1
By N-N-iodosuccinimide (NIS under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the iodo-11-phenyl of product 6--11H-benzo [a] the fluorenol 2a that silica gel column chromatography is separated pure.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 152.3,147.1,142.6,141.8,139.2,137.8,135.1,128.6,128.5,128.4,128.1,127.4,127.2,127.1,126.5,125.2,124.9,124.1,122.5,85.0,83.4; HRMS (EI) calcd for C
23h
15iO (M)
+: 434.0168, found:434.0179.Elemental analysis calcd.For C
23h
15iO:C 63.61, H 3.48; Found:C 63.49, H 3.59.
Example 2
By N-bromo-succinimide (NBS under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the bromo-11-phenyl of product 6--11H-benzo [a] the fluorenol 2b that silica gel column chromatography is separated pure.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.
Example 3
By N-N-iodosuccinimide (NIS under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-phenyl-1-(2-(2-phenylacetylene base-5-fluorine) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the iodo-11-phenyl of the fluoro-6-of product 3--11H-benzo [a] the fluorenol 2c that silica gel column chromatography is separated pure.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 167.7,161.9,159.5,152.4,146.68,146.61,141.9,141.6,138.8,138.6,132.2,132.0,130.8,129.9,129.8,129.4,129.3,128.9,128.8,128.5,128.2,127.3,124.8,124.1,122.6,117.2,117.0,108.7,108.5,83.86,83.83.
Example 4
By N-bromo-succinimide (NBS under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-phenyl-1-(2-(2-phenylacetylene base-5-fluorine) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the bromo-11-phenyl of the fluoro-6-of product 3--11H-benzo [a] the fluorenol 2d that silica gel column chromatography is separated pure.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 167.7,162.1,159.6,151.8,147.5,142.3,138.4,135.6,135.5,135.2,133.2133.1,130.8,128.8,128.5,127.9,127.8,127.3,125.1,124.8,124.0,123.4,117.6,117.3,116.1,110.7,110.5,83.8.
Example 5
By N-N-iodosuccinimide (NIS under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-(4-methoxyl group) phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the iodo-9-methoxyl group of product 6--11-phenyl-11H-benzo [a] the fluorenol 2e that silica gel column chromatography is separated pure.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), 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.
Example 6
By N-bromo-succinimide (NBS under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-(4-methoxyl group) phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the bromo-9-methoxyl group of product 6--11-phenyl-11H-benzo [a] the fluorenol 2f that silica gel column chromatography is separated pure.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.
Example 7
By N-N-iodosuccinimide (NIS under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-(4-ethyl) phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the iodo-9-ethyl of product 6--11-phenyl-11H-benzo [a] the fluorenol 2g that silica gel column chromatography is separated pure.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), 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.
Example 8
By N-bromo-succinimide (NBS under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-(4-ethyl) phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the bromo-9-ethyl of product 6--11-phenyl-11H-benzo [a] the fluorenol 2h that silica gel column chromatography is separated pure.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), 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.
Example 9
By N-N-iodosuccinimide (NIS under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-phenyl-1-(2-(2-is to fluorophenylethynyl) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the iodo-11-of product 6-that silica gel column chromatography is separated pure 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.
Example 10
By iodine (I under nitrogen protection
20.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol), be added drop-wise in the dichloromethane solution of 3-(4-methoxyl group) phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring, at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the iodo-9-methoxyl group of product 6--11-phenyl-11H-benzo [a] the fluorenol 2e that silica gel column chromatography is separated pure.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), 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.
Example 11
By iodine chloride (ICl under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-phenyl-1-(2-(2-phenylacetylene base) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the iodo-11-phenyl of product 6--11H-benzo [a] the fluorenol 2a that silica gel column chromatography is separated pure.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 152.3,147.1,142.6,141.8,139.2,137.8,135.1,128.6,128.5,128.4,128.1,127.4,127.2,127.1,126.5,125.2,124.9,124.1,122.5,85.0,83.4; 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.
Example 12
By simple substance bromine (Br2 under nitrogen protection; 0.36mmol) be dissolved in organic solvent dichloromethane with catalyst A gOTf (0.015mmol); be added drop-wise in the dichloromethane solution of 3-phenyl-1-(2-(2-phenylacetylene base-5-fluorine) phenyl) propargyl-2-alcohol (0.30mmol) at 10 DEG C under stirring; at 10 DEG C, stirring reaction 10-15 hour, TLC detect to complete reaction.React complete, be spin-dried for by solvent, crude product directly goes up the bromo-11-phenyl of the fluoro-6-of product 3--11H-benzo [a] the fluorenol 2d that silica gel column chromatography is separated pure.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.
Example 13
By iodo-for 6-11-phenyl-11H-benzo [a] fluorenol 2a (0.20mmol under nitrogen protection; 1.0equiv), to methylphenylboronic acid (0.21mmol; 1.05equiv) with catalyzer dichloro two triphenyl phosphorus palladium (0.004mmol; 2mol%) and mineral alkali salt of wormwood (0.40mmol, 2.0equiv) be dissolved in mixed organic solvents DMF/H
2in O (2.0mL, 5: 1, v/v), reaction system is heated to 50 DEG C in the lower reaction of stirring 6 hours, TLC detects to complete reaction.React complete, add water (10mL) cancellation reaction, ethyl acetate extracts organism, organic phase saturated brine washs, anhydrous sodium sulfate drying, concentrated after filtering, crude product is directly gone up silica gel column chromatography separation and is obtained pure 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), 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.
Example 14
By iodo-for 6-11-phenyl-11H-benzo [a] fluorenol 2a (0.20mmol under nitrogen protection; 1.0equiv), to methylbenzene acetylene (0.22mmol; 1.10equiv) with catalyzer dichloro two triphenyl phosphorus palladium (0.004mmol; 2mol%), cuprous iodide (0.004mmol; 2mol%) be dissolved in organic solvent triethylamine (2.0mL); reaction system is heated to 50 DEG C to detect to complete reaction in stirring lower reaction 3-4 hour, TLC.React complete, be spin-dried for solvent, thick product is directly gone up silica gel column chromatography separation and is obtained pure 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 152.2,145.0,142.7,139.1,138.9,136,8,134.9,133.5,131.5,129.4,128.9,126.4,128.4,128.7,128.47,128.44,128.2,127.3,127.1,126.1,125.0,124.9,123.9,122.8,120.2,115.3,93.6,87.8,83.7,21.6.HRMS (EI) calcd forC
32h
22o (M)
+: 422.1671, found:422.1688.
Claims (4)
1. a halo benzo [
a] preparation method of fluorenol, it 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-N-halosuccinimides or iodine, simple substance bromine or iodine chloride under catalyst condition, by the close electrocyclic reaction of a series nature, temperature of reaction is 0-15 DEG C, reaction times is 10-15 hour, the efficiently obtained halo benzo of one kettle way [
a] fluorenol, the catalyzer used adopts silver trifluoromethanesulfonate, copper trifluoromethanesulfcomposite or Bismuth triflate.
2. halo benzo according to claim 1 [
a] preparation method of fluorenol, it is characterized in that described 3-aryl-1-(2-(2-virtue ethynyl) phenyl) propargyl-2-alcohol and N-N-halosuccinimides, iodine (I
2), simple substance bromine (Br
2) or the ratio of iodine chloride (ICl) be 1:1.2.
3. a halo benzo according to claim 1 [
a] preparation method of fluorenol, it is characterized in that gained product halo benzo [
a] halogen atom in fluorenol can also continue linked reaction occurs, thus introduce more functional group on product molecule skeleton under the effect of palladium catalyst.
4. halo benzo according to claim 2 [
a] preparation method of fluorenol, it is characterized in that described N-N-halosuccinimides is N-N-iodosuccinimide (NIS), N-bromo-succinimide (NBS) or N-chlorosuccinimide (NCS).
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| Title |
|---|
| A Facile Route to Polysubstituted Naphthalenes and Benzofluorenols via Scandium Triflate- and Triflic Acid- Catalyzed Benzannulation of 2-(2-Alkynylarylidene)-1,3-Dicarbonyl Compounds;LU LIU等;《Adv. Synth. Catal.》;20100728;第352卷;第1920-1924页 * |
| Selectivity Control in Lewis Acid Catalyzed Regiodivergent Tandem Cationic Cyclization/Ring Expansion Terminated by Pinacol Rearrangement;Lu Liu等;《Angew. Chem. Int. Ed.》;20090803;第48卷(第33期);第6093页左栏最后一段以及图1 * |
| Synthesis of the benzo[b]fluorene core of the kinamycins by cycloaromatization of non-conjugated benzotriynes;David Rodríguez等;《Tetrahedron Letters》;19991231;第40卷;第7703页第2段及图3 * |
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