HETEROCYCLES

Paper | Regular issue | Vol. 81, No. 5, 2010, pp. 1157-1168
Received, 28th December, 2009, Accepted, 4th March, 2010, Published online, 5th March, 2010.
DOI: 10.3987/COM-09-11898

■ Synthesis of Diaza-Analogue of Fluorenone and Spirobifluorene

Guo-Hong Wu, Qian-Cai Liu,* and Jie Tang

Department of Chemistry, East China Normal University, 3663 Zhongshan RD(N9, Shanghai 200062, China

Abstract

The effective syntheses of diaza-analogue of fluorenone and spirobifluorene with N=N bond has been conducted with the using of ninhydrin and corresponding acetyl derivatives of arenes. Single-crystal X-ray diffraction of 2-(spirobifluoren-2-yl)- 3,4-dizaspirobifluorene (4a) proved the conformation.

INTRODUCTION
Polycyclic aromatic hydrocarbons (PAHs) have been of great interest especially in materials science because of their utilities in organic electronics, such as light-emitting diodes, field-effect transistors, and solar cells.1 For this reason, development of an efficient and preparative method for simple or functionalized PAHs is considered to be highly important. In particular, fluorene derivatives are a notable structural motif for the diverse PAH derivatives having various applications as precursors for different materials.2 In addition, some type of fluorene-bearing compounds especially aza- and diazafluorenones exhibit interesting bioactivities as monoamine oxidase (MAO) inhibitors.3 They are also frequently utilized as effective ligands in organometallic chemistry.4 Conventional multistep procedures were employed for the synthesis of fluorenes, spirobifluorene (SBF) and their derivatives, which have attracted considerable attention in recent years in the field of organic optoelectronics, owing to their intriguing electronic properties and aesthetic appeal.5 Spirobifluorene could be considered as the joining of two fluorene units through a shared spiro sp3-C atom which was first described by Gomberg in 1930.6 This non-planarity structure could effectively prevent crystals from forming,7 and increase molecular amorphism. Therefore these kinds of compounds generally exhibit high Tg, good thermal stability and excellent solubility in common organic solvents.8 Spiro compounds as organic molecular materials have become promising candidates for optoelectronic devices due to their high energy gap and low HOMO levels.9 Mono-aza-spirobifluorene have been widely studied, however, as for heterocycle-fused spirobifluorene with N=N bond, 2-phenyl-3,4,4’- triazaspiribifluorene (3’-Phenylspiro-[4-azafluorene- 9,5'-indeno[l,2-c] pyridazine] ) is only sample reported so far.10a
Described herein are our most recent studies on the diaza-analogue of fluorenone, spirobifluorene derivatives, the scope and synthetic applicability were quite versatile. This led us to initiate our efforts on the detailed study of diazaspirobifluorenes, which are never studied in detail before. It was revealed that the employment of aromatic acetyl or diacetyl derivatives of aromatics or compounds with methylene-carbonyl moiety as templates through condensation reaction with ninhydrin and hydrazine hydrate in suitable solvents. The present synthetic route to a fluorene motif was quite general, thus allowing the synthesis of a wide range of diazafluorenones to take place smoothly to furnish the corresponding 2-arylfluorenones in moderate to excellent yields. They can be used as precursors for syntheses of previously unknown heterocycle-fused spirobifluorene compounds containing the 4-azafluorene and pyridazine fragments.

RESULTS AND DISCUSSION
Generally, synthsis of diaza-fluorenone could be accomplished by the reaction of ninhydrin with acetyl derivatives of arene and hydrazine hydrate in suitable solvents as described in literatures.3 The reaction of 2-aryl-3,4-diazafluorenone with Grignard reagent or lithium salt generated by 2-bromobiphenyl afforded the tertiary fluoren-9-ol. The reaction conducted either under refluxing (for Grignard reaction) or at lower temperature (-78 °C for lithium salt reaction) afforded 2-aryl-3,4-diazafluoren-9-ol in good yields. Most of the fluoren-9-ol intermediates are separable and easily purified. However, their solubility vary upon different substituents. The conventional conditions with HCl/HOAc system didn’t work for the ring closure reaction of fluoren-9-ols.6 Many efforts were made in order to further convert them into 3,4-diazaspirobifluorene compounds effectively. Among conditions tested, we found that HCO2H/ HCO2Na and PPA systems both can serve as efficient catalysts for the ring closure reaction of fluoren-9-ols into 3,4-diazaspirobifluorenes. Synthesis of compounds 4a and 4b is outlined in Scheme 1.

The Grignard reagent, prepared in situ from 2-bromobiphenyl and Mg in THF, was reacted with fluorenone to form the tertiary fluoren-9-ol, which was cyclized with HCl/HOAc to form spirobifluorene following Gomberg’s procedure.6a The acylation of spirobifluorene with AlCl3 form 2-acetyl spirobifluorene (1a) and 2,2’-diacetylspirobifluorene (1b), which were easily separated by column chromatography. The reaction of 1a or 1b with ninhydrin and hydrazine hydrate in acetic acid under refluxing afford compound 2a or 2b in good yields (70 % and 73.8 % respectively), which could be purified by crystallization from EtOH or CH2Cl2. Again the Grignard reagent of 2-bromobiphenyl was employed to reaction with compounds 2a or 2b to form 3a and 3b. The ring closure reaction of 3a could be completed with PPA and higher temperature10 or with HCO2Na/HCO2H to have better result. Compound 3b was used to form compound 4b directly due to the difficult to purify.
During this attempt, we found that the solubility of intermediates and final products 4a and 4b above are not so good, then we consider the more soluble 9,9-dihexylfluorene for our further targets (Scheme 2).

9,9-Dihexylfluorene (5) was synthesized by the reaction of fluorene and 1-bromohexane. The control acylation of 9,9-dihexylfluorene (5) led to the formation of 2-acetyl-9,9-dihexylfluorene (6a) and 2,7-diacetyl-9,9-dihexylfluorene (6b), which were reacted with ninhydrin and hydrazine hydrate to form compounds 7a and 7b respectively. The lithium salt of 2-bromobiphenyl was used as nucleophilic reagent in order to synthesize alcohol compounds more effectively. Compound 8a can be separated and further converted into compound 9a. However, 8b cannot be purified and thus converted to 9b directly.
In order to have insight of their structure arrangements, the X-ray crystal structure of compound 4a is established. The molecular structure of the title compound is shown in Figure 1.

As shown in Figure1, the title compound contains three fluorene units and one 3,4-diazafluorene moiety, 3,4-diazafluorene unit and one fluorene unit are almost coplanar, and 3,4-diazafluorene units are almost perpendicular to another fluorene unit. The rest of two fluorene units are also approximately perpendicular to each other. The spiro-junction of 2-(spirobifluorene-2-yl)-3,4-diazaspirobifluorene orthogonally arranges two conjugated molecular arms. The bond lengths of N=N and C=N are 1.324(6) Å (for N1-N2), 1.403(7) Å (for N1-C45), 1.370(5) Å (for N2-C48) Å, respectively. The dihedral angles of two fluorenyl rings of spirobifluorenes are 92.3 ° (with N-N bond)and 92.8 °, respectively.

EXPERIMENTAL
1. Instruments and materials
Melting point was measured on an X-4 micrographic melting point apparatus. 1H NMR and 13C NMR spectra were measured on a Bruker DR × 500 spectrometer (1H NMR 500 MHz, 13C NMR 125 Hz). Data for X-ray structure analysis were collected on a Bruker-AXS detector with Mo Ka radiation (λ=0.71073Å). Structures were solved by direct methods with SHELXTL (version 6.10). Element analyses were measured on Vario EL III element analysis instrument. Mass spectra were measured either on Agilent 5973N mass spectrometer or micOTOF II (ESI) spectrometers.
2. Synthesis
Synthesis of 2-(spirobifluoren-2-yl)-3,4-diazafluorenone (2a)
Using 2-bromobiphenyl as starting material, the intermediates 1a and 1b was obtained by literature method.11 The solution of 2-acetyl-9,9'-spirobifluorene (1a) (3.1 g, 8.65 mmol) and ninhydrin (1.54 g, 8.65 mmol) in 50 mL of glacial acetic acid was heated to reflux for 3-4 h. Then the reaction mixture was allowed to cool to room temperature and hydrazine hydrate (85%, 5.5 mL, 13 mmol) was added dropwise and the stirring was continued for 3 h. The resulting yellow solid was collected by filtration and recrystallized from EtOH. Yield (70%). mp 263-265 °C. 1H NMR (CDCl3, 500 MHz) δ: 8.25 (dd, J = 8Hz, J = 1.5Hz , 1H), 8.11 (d, J = 8Hz, 1H), 8.02 (d, J = 8Hz, 1H), 7.92 (d, J = 8Hz, 1H), 7.89 (d, J = 7.5Hz, 2H), 7.81 (d, J = 8.5Hz, 2H), 7.71 (t, J = 7Hz, 1H), 7.53 (t, J = 7.5Hz, 1H), 7.47 (s, 1H), 7.43-7.37 (m, 3H), 7.17 (t, J =7.5Hz, 1H), 7.13 (d, J = 7.5Hz, 2H), 6.77 (t, J = 7.5Hz, 3H). 13C NMR (CDCl3, 125MHz) δ: 190.35, 160.22, 159.79, 149.96, 149.57, 148.02, 144.37, 142.23, 141.87, 140.71, 136.37, 135.20, 134.73, 131.82, 130.71, 128.68, 127.96, 127.92, 127.89, 127.00, 125.12, 124.19, 123.95, 122.64, 122.19, 120.64, 120.57, 120.21, 117.29, 65.98. Anal. Calcd for C36H20N2O: C, 87.08; H, 4.06; N, 5.64. Found: C, 87.22; H, 3.97; N, 5.56. MS (EI): m/z=496 [M+].
Synthesis of 2,7-di-3,4-diazafluorenone-9,9'-spirobifluorene (2b)
The solution of 2,7-diacetyl-9,9'-spirobifluorene (1b) (4.09 g, 22.95 mmol) and ninhydrin (4.59 g, 11.47 mmol) in 150 mL of glacial acetic acid was heated to reflux for 3-4 h. Then the reaction mixture was allowed to cool to room temperature and hydrazine hydrate (85%, 1.46 mL, 33.41 mmol) was added dropwise and the stirring was continued for 3 h. The resulting yellow solid was collected by filtration and recrystallized from CH2Cl2.Yield (73.8%). mp 240 °C (dec.). 1H NMR (CDCl3, 500MHz) 8.25 (d, J = 8Hz, 2H), 8.09-8.03 (m, 4H), 7.96 (d, J = 8Hz, 2H), 7.83 (s, 2H), 7.79 (d, J = 7.5Hz, 2H), 7.69 (t, J =7.5Hz, 2H), 7.55 (s, 2H), 7.51 (t, J =7.5Hz, 2H), 7.44 (t, J = 7.0Hz, 2H), 7.18 (t, J = 7.5Hz, 2H), 6.82 (d, J = 8.0Hz, 2H). Anal. Calcd for C47H24N4O2: C, 83.42; H, 3.57; N, 8.28. Found: C, 83.02; H, 3.63; N, 7.96. MS (EI): m/z =676[M+].
Synthesis of 2-(spirobifluoren-2-yl)-9-(2-biphenyl)-3,4-diazafluoren-9-ol (3a)
A flask charged with 2-biphenylmagnesium bromide, prepared in advance from 2-bromobiphenyl (4.29 g, 18.4 mmol) and magnesium (0.44 g, 18.4 mmol ) in THF (50 mL), was added under refluxing a solution of 2a (3.15 g, 6.14 mmol) in THF (40 mL) under N2. The mixture was refluxed for 12 h. The reaction mixture was quenched with saturated aqueous NH4Cl after cooling to ambient temperature, and subsequently extracted with CH2Cl2. The combined organic extracts were washed and dried (Na2SO4) and filtered, and the solvents were concentrated by rotary evaporation. The resulting crude product was wash with hexanes and further purified by column chromatography on silica gel by using of CH2Cl2:AcOEt (20:1). Yield (61%). mp 198 °C (dec.). 1H NMR (CDCl3, 500MHz) δ: 8.43 (d, J = 7.5Hz, 1H), 8.17 (d, J = 8Hz, 1H), 8.11-8.05 (m, 4H), 7.62 (s, 1H), 7.60-7.57 (m, 2H), 7.46-7.38 (m, 5 H), 7.35 (t, J = 8.5Hz, 2H), 7.23-7.13 (m, 4H), 6.83 (d, J = 7 Hz, 1H), 6.75-6.65 (m, 4H), 6.58 (s, 1H), 6.51 (brs, 1H), 6.43 (brs, 1H), 6.11 (brs, 1H), 5.72 (brs, 1H); 13C NMR (CDCl3, 125 MHz) δ: 159.79, 156.82, 151.75, 149.48, 148.35, 143.21, 141.75, 141.02, 140.33, 139.26, 136.65, 136.61, 131.31, 129.57, 128.53, 127.84, 127.35, 126.37, 125.29, 124.00, 123.96, 121.98, 121.25, 121.07, 119.57, 80.11, 65.93. Anal. Calcd for C48H30N2O: C, 88.59; H, 4.65; N, 4.30. Found: C, 88.24; H, 4.74; N, 4.25. MS (EI): m/z = 650 [M+].
Synthesis of 2-(spirobifluoren-2-yl)-3,4-diazaspirobifluorene (4a)
A mixture of 1.5 g (0.97 mmol) of 3a and 40 mL of polyphosphoric acid was heated for 10 h at 200 °C. After cooling water (250 mL) was added. The reaction products were repeatedly with CH2Cl2 and dried with Na2SO4 .The crude product was purified by column chromatography on a silica gel by using of CH2Cl2: AcOEt (10:1). Yield (60%). mp 388-390 °C. Single crystals of 4a used for data collection were obtained by slowly evaporating a solution in acetone at room temperature. 1H NMR (CDCl3, 500MHz) δ: 8.32 (d, J = 7.5Hz, 1H), 7.97 (dd, J = 7.5Hz, 1.5Hz, 1H), 7.87-7.82 (m, J = 7.5Hz, 6H), 7.49-7.42 (m, 2H), 7.40 (t, J = 7.5Hz, 2H), 7.37-7.33 (m, 3H), 7.27 (t, J = 7.5Hz, 1H), 7.13-7.05 (m, 6H), 6.73 (d, J = 7.65Hz, 1H), 6.74-6.68 (m, 5H); 13C NMR (CDCl3, 125MHz) δ: 157.42, 149.65, 149.05, 148.21, 147.91, 146.37, 143.56, 141.83, 141.78, 136.21, 131.21, 128.74, 128.33, 128.25, 127.80, 127.15, 124.07, 123.99, 123.96, 122.94, 121.94, 120.40, 120.34, 120.18, 120.08, 118.90, 65.98, 63.74. Anal. Calcd for C48H28N2: C, 91.11; H, 4.46; N, 4.43. Found: C, 90.88; H, 4.96; N, 4.21. MS (EI): m/z=635 [M+1]+.
2,2’-Bis(3,4-diaza-9,9'-spirobifluoren-2-yl)-9,9-spirobifluorene (4b)
A flask charged with 2-biphenylmagnesium bromide, prepared in advance from 2-bromobiphenyl (4.29 g, 18.4 mmol) and magnesium (0.44 g, 18.4 mmol) in THF (50 mL), was added under refluxing a solution of 2b (3.15 g, 6.14 mmol) in THF (40 mL) under N2. The mixture was refluxed for 12 h. After cooling to ambient temperature, the reaction mixture was quenched with saturated aqueous NH4Cl and extracted with CH2Cl2. After workup, the residue was crystallized from petroleum ether, the solid was filtered and washed with CH2Cl2 to remove any trace of impurity and subsequently dissolved in the mixture of HCOONa and HCOOH with refluxing for few hours. The mixture was then cooled, diluted with water, and extracted with CH2Cl2. The combined organic extracts were washed with saturated aqueous NaHCO3, water, brine. Then the organic phase was dried over Na2SO4, and filtered, the solvent was removed under reduced pressure, the residue was purified by column chromatography on silica gel by using of CH2Cl2:EtOAc (10:1) to give a white solid which tends to turn to yellow on storage. mp 256 °C (dec.). 1H NMR (CDCl3, 500MHz) δ:8.29 (d, J = 7.8Hz, 2H), 7.92 (dd, J = 7.8Hz, J =1.5Hz, 2H), 7.83 (t, J = 8.3Hz, 8H), 7.46 (t, J = 7.1Hz, 4H), 7.39 (q, J = 7.3Hz, 4H), 7.33 (t, J = 7.2Hz, 2H), 7.27 (s, 1H), 7.12-7.05 (m, 9H), 6.72 (d, J = 7.7Hz, 2H), 6.68-6.66 (m, 6H). Anal. Calcd for C71H40N4: C, 89.85; H, 4.25; N, 5.90. Found: C, 89.15; H, 4.55; N, 5.98. MS(ESI): Calcd for C71H40N4 949.1238; Found: 949.3325.
Synthesis of 9,9'-dihexylfluorene (5)
A solution of fluorene (8 g, 48.13 mmol) in THF (40 mL) was treated with BuLi (19.3 mL, 2.5 M in hexane, 48.13 mmol) under argon at -78 °C. The mixture was stirred at -78 °C for 45 min. A solution of 1-bromohexane (7.94 g, 48.13 mmol) in THF (20 mL) was added dropwise. After addition was complete, the reaction mixture was left to stirred at -78 °C for 1.5 h and then left to room temperature. The reaction mixture was then re-cooled to -78 °C and 1-bromhexane (7.94 g, 48.13 mmol) was added. The reaction mixture was allowed to room temperature overnight and the whole lithiation and alkylation process repeated. The reaction was quenched with H2O and extracted with CH2Cl2. The organic fraction was dried MgSO4 and the solvent was removed under reduced pressure. Yield (96%). 1H NMR (CDCl3, 500MHz) δ: 7.71 (dd, J = 6.5Hz, J = 1Hz, 2H), 7.36-7.29 (m, 6H), 1.99-1.96 (m, 4H), 1.14-1.08 (m, 4H), 1.05-1.03 (m, 8H), 0.79-0.76 (m, 6H), 0.66-0.61 (m, 4H).
Synthesis of 2-acetyl-9,9'-dihexylfluorene (6a)
A mixture of 5 (18 g, 53.8 mmol), anhydrous AlCl3 (8.62 g, 64.56 mol) and 200 mL of dry CH2Cl2 was cooled below 0-5 °C with an ice-bath, and acetyl chloride (3.83 mL, 53.8 mol) was added dropwise. The mixture was heated to reflux for 6 h, then poured into 250 mL of ice-water containing 45 mL of conc HCl and stirred to reach room temperature. The organic phase was separated, and the aqueous layer was washed with CH2Cl2. The combined organic phase was washed with H2O, 10% aqueous NaOH, H2O and brine, dried over MgSO4, then the solvent was removed. The residue was purified by column chromatography on silica gel by using of CH2Cl2:PE (1:3). Yield 8.7 g ( 43%) as a tan liquid. 1H NMR (CDCl3, 500MHz) δ: 7.99 (s, 1H), 7.96 (d, J = 7.9Hz, 1H), 7.75-7.74 (m, 2H), 7.39-7.33 (m, 3H), 2.05-2.00 (m, 4H), 1.10-1.02 (m, 12H), 0.76-0.74 (m, 6H), 0.60-0.59 (m, 4H).
Synthesis of 2,7-diacetyl-9,9'-dihexylfluorene (6b)
A mixture of 5 (15.5 g, 46.33 mmol), anhydrous AlCl3 (20 g, 0.15 mol) and 200 mL of dry CH2Cl2 was cooled below 0-5 °C with an ice-bath, and acetyl chloride (9.6 mL, 0.135 mol) was added dropwise. The mixture was heated to reflux for 12 h, then poured into 250 mL of ice-water containing 60 mL of conc HCl and stirred to reach room temperature. The organic phase was separated, and the aqueous layer was washed with CH2Cl2. The combined organic phase was washed with H2O, 10% aqueous NaOH, H2O and brine, dried over MgSO4, then the solvent was removed. The residue was purified by column chromatography on silica gel with CH2Cl2:PE (1:3). Yield (30.9%) as a pale-yellow liquid. 1H NMR (CDCl3, 500MHz) δ: 8.34 (s, 1H), 7.98-7.95 (m, 3H), 7.82 (d, J = 8.5Hz, 1H), 7.44 (d, J = 7.9Hz, 1H), 2.02-1.99 (m, 4H),1.06-0.96 (m, 12H), 0.71-0.68 (m, 6H), 0.53-0.52 (m, 4H).
Synthesis of 2-(9,9'-dihexylfluorenyl )-3,4-diazafluorenone (7a)
The solution of 6a (5 g, 13.28 mmol) and ninhydrin (2.32 g, 13.28 mmol) in 150 mL of glacial acetic acid was heated to reflux for 3 h. Then the reaction mixture was allowed to cool to room temperature and hydrazine hydrate (85%, 0. 85 mL, 19.92 mmol) was added dropwise and the stirring was continued for 3 h. and further chromatographed on silica gel by using of CH2Cl2:PE (1:1). Yield (37.2%). mp 109-111 °C. 1H NMR (CDCl3, 500MHz) δ: 8.25 (s, 1H), 8.22 (d, J = 7.5Hz, 1H), 8.13 (t, J = 7.5Hz, 2H), 7.89-7.87 (m, 2H), 7.80-7.76 (m, 2H), 7.58 (t, J = 7.4Hz, 1H), 7.43-7.38 (m, 3H), 2.10-2.06 (m, 4H), 1.14-1.06 (m, 12H), 0.78-0.75 (m, 6H), 0.70-0.68 (m, 4H). 13C NMR (CDCl3, 125MHz) δ: 190.53, 160.38, 160.23, 151.75, 151.47, 143.87, 142.38, 140.05, 136.42, 134.81, 134.33, 131.82, 130.92, 127.90, 126.92, 125.99, 125.15, 122.97, 122.21, 121.45, 120.29, 120.20, 117.42, 55.36, 40.32, 31.44, 29.63, 23.75, 22.51, 13.92. Anal. Calcd for C36H38N2O: C, 84.01; H, 7.44; N, 5.44. Found: C, 84.31; H, 7.67; N, 5.50. MS (EI): m/z = 514 [M+].
Synthesis of 2,7-di(3,4-diazafluorenonyl )-9,9'-dihexylfluorene (7b)
The solution of 6b (3.34 g, 7.98 mmol) and ninhydrin (2.82 g, 15.96 mmol) in 150 mL of glacial acetic acid was heated to reflux for 3-4 h. Then the reaction mixture was allowed to cool to room temperature and hydrazine hydrate (85%, 1.19 mL, 27.93 mmol)) was added dropwise and the stirring was continued for 3 h. the mixture was then cooled, diluted with water, and extracted with CH2Cl2. The combined organic extracts were washed with saturated aqueous NaHCO3, water, brine. After the organic phase was dried over Na2SO4, and filtered, the solvent was removed under reduced pressure, The residue was purified by column chromatography on silica gel using CH2Cl2:EtOAc (20:1). Yield (23.67%). mp 240-242 °C. 1H NMR (CDCl3, 500MHz) δ: 8.59 (s, 1H), 8.27(s, 1H), 8.23 (t, J = 7.8Hz, 2H), 8.16 (dd, J = 7.5Hz, J = 1.5Hz, 1H), 8.13 (d, J = 7.5Hz, 3H), 7.99 (d, J = 8Hz, 1H), 7.90 (d, J = 7.5Hz, 2H), 7.91 (d, J = 7.5Hz, 2H), 7.61-7.57 (m, 3H), 2.10-2.05 (m, 4H), 1.12-1.03 (m, 12H), 0.76-0.69 (m, 10H). 13C NMR (CDCl3, 125MHz) δ: 189.28, 189.21, 159.37, 159.19, 159.07, 153.26, 150.79, 141.86, 141.14, 140.14, 135.27, 133.86, 133.76, 133.67, 133.65, 130.76, 130.73, 129.84, 129.79, 125.68, 125.10, 124.01, 122.54, 121.16, 121.09, 120.41, 119.51, 117.86, 116.31, 54.54, 39.15, 30.28, 28.45, 22.71, 21.34, 12.76. Anal. Calcd for C47H42N2O2: C, 81.24; H, 6.09; N, 8.06. Found: C, 81.22; H, 6.24; N, 7.86. MS (EI): m/z = 694[M+].
Synthesis of 2-(9,9'-dihexylfluorenyl)-9-(2-biphenyl)-3,4-diazafluoren-9-ol (8a)
A solution of 2-bromobiphenyl (1.45 g, 6.22 mmol) in THF (20 mL) was treated with BuLi (2.74 mL, 2.5 M in hexane, 6.84 mmol) under argon at -78 °C. The mixture was stirred at -78 °C for 45 min. And a solution of 7a (1.6 g, 3.11 mmol) in THF (20 mL) was added dropwise. The resulting mixture was stirred at -78 °C for 1 h, and at room temperature for 12 h. The organic layer was washed with water and brine, dried over Na2SO4, and filtered. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel by using of CH2Cl2:PE (5:1) as eluant to afford 8a. Yield (33.4%). mp 186-188 °C. 1H NMR (CDCl3, 500MHz) δ: 8.61(d, J = 8.1Hz, 1H), 7.96 (s, 1H), 7.70 (q, J = 8.5Hz, 3H), 7.58 (t, J = 7.7Hz, 1H), 7.53 (s, 1H), 7.40-7.30 (m, 5H), 7.21 (d, J =7.5 Hz, 1H), 7.07 (t, J = 7.1Hz, 1H), 6.98 (t, J = 7.2Hz, 1H), 6.92 (d, J = 7.4Hz, 1H), 6 .77 (t, J = 7.3Hz, 1H), 6.53-6.47 (m, 2H), 6.11 (d, J = 6.8Hz, 1H), 5.73 (d, J = 6.1Hz, 1H), 5.07 (brs, 1H), 2.09-2.04 (m, 4H), 1.10-1.03 (m, 12H), 0.74-0.68 (m, 10H). 13C NMR (CDCl3, 125MHz) δ: 159.10, 157.65, 151.35, 151.33, 150.50, 149.06, 142.89, 140.53, 140.32, 139.66, 138.01, 135.51, 134.93, 131.12, 131.05, 129.34, 129.14, 128.60, 127.61, 127.54, 126.85, 126.76, 126.30, 126.01, 124.94, 122.96, 121.55, 121.31, 120.13, 119.77, 119.56, 80.27, 55.33, 40.35, 31.51, 29.66, 23.82, 22.52, 13.94. Anal. Calcd for C48H48N2O: C, 86.19; H, 7.23; N, 4.19. Found: C, 86.46; H, 7.43; N, 4.19. MS (EI): m/z = 650 [M-H2O]+.
Synthesis of 2-(9,9'-dihexylfluorenyl)-3,4-diazaspirobifluorene (9a)
A mixture of 8a, HCOONa and HCOOH (50 mL) was refluxed for 20 h. The mixture was then cooled, diluted with water, and extracted with CH2Cl2. The combined organic extracts were washed with saturated aqueous NaHCO3, water, brine. After workup, the residue was purified by column chromatography on silica gel using CH2Cl2 to give a white solid (0.35 g, yield 74.3%). mp 213-215 °C. 1H NMR (CDCl3, 500MHz) δ: 8.42 (d, J = 7.7Hz, 1H), 8.20 (s, 1H), 7.92 (d, J = 7.7Hz, 2H), 7.77 (dd, J = 8Hz, J = 1.4Hz, 1H), 7.69 (q, J = 5.8Hz, 2H), 7.54 (t, J = 7.5Hz, 1H), 7.46 (t, J = 7.5Hz, 2H), 7.34-7.29 (m, 5H), 7.19 (t, J = 7.5Hz, 2H), 6.81 (d, J = 7.6Hz, 3H), 2.02-1.96 (m, 4H), 1.06-0.96 (m, 12H), 0.72-0.69 (m, 6H), 0.59 (m, 4H). 13CNMR (CDCl3, 125MHz) δ: 161.59 , 157.89, 151.56, 151.41, 149.02, 148.19, 146.60, 142.96, 141.87, 140.29, 137.83, 135.11, 131.26, 128.87, 128.61, 128.33, 127.57, 126.76, 125.82, 124.19, 122.94, 122.03, 121.65, 120.4455, 120.07, 119.71, 118.79, 63.75, 55.34, 40.29, 31.44, 29.61, 23.70, 22.51, 13.93. Anal. Calcd for C48H46N2: C, 88.57; H, 7.12; N, 4.30. Found: C, 88.61; H, 7.39; N, 4.25. MS (EI): m/z = 650 [M+].
Synthesis of 2,7-bis(3,4-diazaspirobifluoren-2-yl)-9,9'-dihexylfluorene (9b)
A solution of 2-bromobiphenyl (1.68 g, 7.21 mmol) in THF (20 mL ) was treated with BuLi (2.88 mL, 2.5 M in hexane, 7.21 mmol ) under argon at -78 °C. The mixture was stirred at -78 °C for 45 min. A solution of 7b (1 g, 1.44 mmol) in THF (20 mL) was added dropwise. The resulting mixture was stirred at -78 °C for 2 h, and then kept at room temperature for 12 h. The organic layer was washed with water and brine, dried over Na2SO4, and filtered. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel using CH2Cl2:EtOAc (10:1). A mixture of fluoren-9-ol and HCOONa and HCOOH (30 mL) was refluxed for 24 h, cooled, diluted with water, and extracted with CH2Cl2. The combined organic extracts were washed with saturated aqueous NaHCO3, water, brine. After workup, the residue was purified by column chromatography on silica gel using CH2Cl2:EtOAc (15:1) to give a solid ( yield 32%). mp 197 °C (dec.). 1H NMR (CDCl3, 500MHz) δ: 8.42 (t, J = 7.8Hz, 2H), 8.20 (s, 1H), 8.31 (s, 1H), 7.93-7.89 (m, 5H), 7.76-7.71 (m, 2H), 7.54 (t, J = 7.5Hz, 2H), 7.45 (q, J = 6.6Hz, 4H), 7.37-7.28 (m, 5H), 7.17 (q, J = 6.5Hz, 4H), 6.82-6.78 (m, 6H), 2.02-1.96 (m, 4H), 1.03-0.96 (m, 10H), 0.69-0.66 (m, 4H), 0.58-0.55 (m, 8H). 13C NMR (CDCl3, 125MHz) δ: 161.72, 161.61, 157.86, 157.74, 153.35, 151.68, 149.00, 148.93, 148.37, 148.23, 146.51, 142.37, 141.84, 141.19, 137.78, 135.47, 131.29, 128.85, 128.61, 128.31, 126.69, 125.88, 124.23, 124.11, 123.22, 122.11, 122.01, 121.63, 120.44, 120.15, 118.97, 118.90, 118.80, 63.83, 63.80, 55.45, 40.25, 39.07, 31.37, 29.53, 23.70, 22.45, 22.39, 13.89. Anal. Calcd for C71H58N4: C, 88.16; H, 6.04; N, 5.79. Found: C, 87.92; H, 6.13; N, 5.61. MS (ESI): Calcd for C71H58N4 967.2660. Found 967.4769.
Crystal data and structure determination
A single crystal of 4a with dimensions of 0.55 mm × 0.47 mm × 0.12 mm was chosen for X-ray diffraction analysis performed on a Bruker-AXS diffractometer, equipped with Mo Ka radiation (λ= 0.71073 Å ) at 296(2) K by using a φ-ω scan mode. In the ranges of 1.39≤θ≤25.01°, a total of 18678 reflections were collected including 5288 unique ones (R int = 0.0327), of which 5288 were observed with I > 2σ(I). The structure was solved by direct methods using SHELXS program of the SHELXL-97 package and refined with SHELXL. The final refinement was performed by full-matrix least-squares method with anisotropic thermal parameters on F2 for the non-hydrogen atoms. 4a (C48H28N2, Mr = 632.72), crystallizes in the monoclinic system, space group CC with a = 13.8523(6), b = 29.3297(13), c = 8.6397(4) Å, β =111.8760(10), V = 3257.4(3) Å3, Z = 4, Dc = 1.290mg/m3, μ = 0.075mm−1, F(000) = 1320, the final R1 = 0.0425 and wR2 = 0.1110 for 5288 observed reflections (I > 2σ(I)). The hydrogen atoms were located from Fourier difference maps. The final R1 = 0.0425, wR2 = 0.1110 (w = 1/[σ2(Fo2) + (0.0628P)2 + 1.12P], where P = (Fo2 + 2Fc 2)/3, (Δ/σ)max = 0.000, S = 1.025, (Δρ) max = 0.139 and (Δρ) min = –0.164 e/Å3.

ACKNOWLEDGEMENTS
The authors thank the Shanghai Natural Science Foundation (Contract No. 09ZR1409400), China for financial support. We also thank the Laboratory of Organic Functional Molecules, the Sino-French Institute of ECNU for Support.

References

1. (a) M. Bendikov, F. Wudl, and D. F. Perepichka, Chem. Rev., 2004, 104, 4891; CrossRef (b) J. E. Anthony, Chem. Rev., 2006, 106, 5028; CrossRef (c) A. R. Murphy and J. M. J. Frechet, Chem. Rev., 2007, 107, 1066. CrossRef
2. (a) M. T. Bernius, M. Inbasekaran, J. O’Brien, and W. Wu, Adv. Mater., 2000, 12, 1737; CrossRef (b) U. Scherf, and E. J. W. List, Adv. Mater., 2002, 14, 477. CrossRef
3. (a) L. R. Morgan, K. Thangaraj, B. LeBlanc, A. Rodgers, L. T. Wolford, C. L. Hooper, D. Fan, and B. S. Jursi, J. Med. Chem., 2003, 46, 4552; CrossRef (b) A. Carroti, V. Carta, F. Campagna, C. Altomare, and G. Casini, Il Farmaco, 1993, 48, 137; (c) S. Kneubuehler, U. Thull, C. Altomare, V. Carta, P. Gaillard, P. A. Carrupt, A. Carroti, and B. Testa, J. Med. Chem., 1995, 38, 3874; CrossRef (d) A. Carroti, M. Catto, F. Leonetti, F. Campagna, R. Soto-Otero, E. Mendez-Alvarez, U. Thull, B. Testa, and C. Altomare, J. Med. Chem., 2007, 50, 5364; CrossRef (e) C. Altomare, S. Cellamare, L. Summo, M. Catto, A. Carotti, U. Thull, P. A. Carrupt, B. Testa, and H. Stoeckli-Evans, J. Med. Chem., 1998, 41, 3812. CrossRef
4. C. A. Fleckenstein and H. Plenio, Chem. Eur. J., 2007, 13, 2701. CrossRef
5. Z. Jiang, H. Yao, Z. Zhang, C. Yang, Z. Liu, Y. Tao, J. Qin, and D. Ma, Org. Lett., 2009, 11, 2607. CrossRef
6. (a) R. G. Clarkson and M. Gomberg, J. Am. Chem. Soc., 1930, 52, 2881; CrossRef (b) A. Aviram, J. Am. Chem. Soc., 1988, 110, 5687. CrossRef
7. J. Pei, B. Liu, Q. Ni, and X. H. Zhou, Acta Chem. Sinica, 2001, 59, 1712.
8. T. P. I. Saragi, T. Spehr, A. Siebert, T. Fuhrmann-Lieker, and J. Salbeck, Chem. Rev., 2007, 107, 1011 and references therein. CrossRef
9. C.-C. Wu, Y.-T. Lin, K.-T. Wong, R.-T. Chen, and Y.-Y. Chien, Adv. Mater., 2004, 16, 61. CrossRef
10. A. Mustafa, M. N. Mikhailova, N. I. Golovtsov, and N. S. Prostakov, Chem. Heterocycl. Compds., 1992, 1155. CrossRef
11. (a) G. Haas and V. Prelog, Helv. Chim. Acta, 1969, 52, 1202; CrossRef (b) L. Mattiello and L. Rampazzo, J. Chem. Soc., Perkin Trans. 2, 1993, 2243. CrossRef