Preparation of 2,7-diaminofluorenone derivatives by palladium catalyzed amination [1]

Article abstract of DOI:10.1007/PL00013499

A convenient synthesis of tert-2,7-diaminofluorenonens 3a-3e via palladium catalyzed reaction of secondary amines with 2,7-dibromofluorene and subsequent oxidation is described. In the cases were non-cyclic secondary amines are applied, the aniline derivatives 4c-4e are formed as side products by a dehydrohalogenation reaction.

Full text of DOI:10.1007/PL00013499

Monatshefte fuÈr Chemie 129, 915±920 (1998)
Preparation of 2,7-Diamino¯uorenone
Derivatives by Palladium Catalyzed
Amination [1]
Junes Ipaktschi1;Ã and Ali Shari®2
1
È
Institut fuÈr Organische Chemie der Universitat Gieûen, D-35392 Gieûen, Germany
2
Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran
Summary. A convenient synthesis of tert-2,7-diamino¯uorenonens 3a±3e via palladium catalyzed
reaction of secondary amines with 2,7-dibromo¯uorene and subsequent oxidation is described. In the
cases were non-cyclic secondary amines are applied, the aniline derivatives 4c±4e are formed as side
products by a dehydrohalogenation reaction.
Keywords. Catalysis; Palladium; Palladacycle; Diamination; Aminostannane; Air oxidation.
Darstellung von 2,7-Diamino¯uorenonderivativen durch palladiumkatalysierte Aminierung [1]
È
Zusammenfassung. Eine einfache Synthese der tertiaren 2,7-Diamino¯uorenone 3a±3e durch
È
palladiumkatalysierte Umsetzung von sekundaren Aminen mit 2,7-Dibrom¯uoren und anschlieûende
È
Oxidation wird beschrieben. Bei der Umsetzung mit offenkettigen sekundaren Aminen werden durch
eine Dehydrohalogenierungsreaktion auch die Anilinderivate 4c±4e als Nebenprodukte gebildet.
Introduction
Recently, the palladium catalyzed intramolecular and intermolecular coupling of
aryl halides with amines has been shown to be a mild and ef®cient method for the
synthesis of aniline derivatives [2, 3]. This important discovery opens up a new
avenue for the synthesis of many interesting organic molecules that are otherwise
dif®cult to prepare [4]. During the course of our studies on dyestuff with an
absorbance in the near infrared region, we were interested in the preparation of 2,7-
diamino¯uorenone derivatives [1].
In this paper we describe a two-step preparation of the ketones 3a±3d via the
diamination of 2,7-dibromo¯uorene (1) with secondary amines (2a±2d) in the
presence of sodium tert-butoxide in toluene with PdCl2[P(o-tolyl)3]2 as catalyst
and, alternatively, a direct diamination of ¯uorenone 5 with the aminostannane
reagent 6 to 3e.
Ã
Corresponding author

916
J. Ipaktschi and A. Shari®
Results and Discussion
Due to the sensitivity of ¯uorenones toward strong bases such as sodium tert-
butoxide [5], palladium catalyzed amination of 5 afforded the corresponding
tertiary amines only in very low yields. For this reason, it was necessary ®rst to
aminate 1 and then to oxidize the product with oxygen to the corresponding
¯uorenone derivatives. According to this procedure, the reaction of dibromide 1
with 2.6 eq. of amine 2a in the presence of 2.8 eq. of NaOC(CH3)3 and 2 mol% of
PdCl2[P(o-tolyl)3]2 in toluene at 100ꢀC leads in a yield of 52% to ketone 3a after
oxidation of the reaction products by oxygen in pyridine/triton B. Similarly,
amination with 2b produced ketone 3b in 25% yield.
In addition to the diamination products, monoamino dehydrohalogenated
¯uorenone derivatives resulting from a reduction reaction were also obtained as
side products in variable amounts. As an example, the amination of 1 with
methylphenylamine (2c) afforded 60% of the diamine 3c and 10% of the
monoamine 4c. Furthermore, the addition of 2d lead to 36% of 3d and 6% of 4d.
To avoid the ring opening reaction in the amination reaction of ¯uorenone
derivatives in the presence of a strong base, we investigated the diamination using
aminostannane reagent 7. In this case, the reaction of 5 with 3 eq. of 7 and 3 mol%
of PdCl2[P(o-tolyl)3]2 afforded 42% of the diamino ¯uorenone derivative 3e and
1% of 4e after 6 h. Recently, the palladacycle 8 ± which is formed by heating of
P(o-tolyl)3 in acetic acid in the presence of (CH3COO)2Pd ± was introduced as an
ef®cient catalyst for the Heck coupling of aryl bromides [6]. To test the suitability
of this catalyst for the amination reaction we investigated the above reaction in the
presence of 3 mol% of 8. With this catalyst, only a weak improvement of the yield
is observed. After 6 h, 58% of 3e and 8% of 4e were formed.

2,7-Diamino¯uorenones
917
Table 1. UV/Vis absorbance maxima ((ꢁmax (lg")) of amino¯uorenones in CH2Cl2
3a
3b
3c
3d
3e
4c
4d
4e
6a
244 (4.33)
222 (4.01) 252 (4.30) 240 (3.95) 236 (4.04)
305 (4.55) 290 (4.54) 301 (4.56) 298 (4.63) 298 (4.56) 293 (4.38) 288 (4.48) 289 (4.52) 284 (4.71)
378 (4.43) 344 (4.15) 360 (4.47) 357 (4.37) 362 (4.37) 346 (4.12) 343 (3.98) 348 (4.13) 328 (4.14)
553 (3.12) 530 (2.72) 530 (2.72) 573 (2.80) 602 (2.81) 501 (2.95) 506 (2.85) 529 (2.97) 511 (2.98)
a In ethanol [12]
Reports on the mechanism of Pd/P(o-tolyl)3-catalyzed aryl amination reactions
suggest that the use of P(o-tolyl)3 favors the formation of monophosphine Pd0
species (L-Pd) which are believed to be the catalytically active species [2, 3].
Oxidative addition of an aryl bromide then forms the dimeric Pd(II) intermediate
[Ar-Pd(L)-Br]2 which has been shown to result from addition of an amine to the
monomeric Pd(II)-amine complex [Ar-Pd(L)(HNR1R2)-Br]. Elimination of HBr
affords the Pd(II)-amidocomplex[Ar-PdII(L)NR1R2] which can undergo reductive
elimination to the desired arylamines. Alternately, in cases were a ꢀ-hydrogen
atom is present in this intermediate (e.g. addition of amines 2c and 2d), reversible
ꢀ-hydride elimination leads to the formation of the dehydrohalogenated side
products 4c and 4d [2a, 3d, 7].
In Table 1, the UV/Vis data of the amino ¯uorenones prepared are listed. As
shown in this Table, 3e (ꢁmax ˆ 602 nm) exhibits the most pronounced bath-
ochromic shift in this category.
Experimental
All reported yields are isolated yields. Catalysts were prepared from palladium chloride [8] and
palladium acetate [6] with tri(o-tolyl)phosphine. Dibromo¯uorene (1) [9] and dibromo¯uorenone (5)
[10] were prepared from ¯uorene. Diethylaminotributylstannane (7) was prepared by reaction of
diethylaminomagnesium bromide with tributhyltin chloride [11]. All melting points are uncorrected
1
and were measured on a BuÈchi SMP-20 melting point apparatus. H NMR and 13C NMR spectra
were recorded on Bruker AM-400 and Bruker AM-200 spectrometers in CDCl3 solutions with TMS
as internal references. IR spectra were run on a Bruker IFS 25 instrument. UV and visible spectra
were measured in dichloromethane solution on a Hewlett-Packard 8452A spectrophotometer with a
diode array detector. Mass spectra were taken using a Varian MAT 311 mass spectrometer. CHN
analyses were obtained using a Carlo-Erba analyzer instrument (model 1104); they were found to
agree satisfactorily with the calculated values.
General procedure for the palladium catalyzed amination of 2,7-dibromo-¯uorene
to the ¯uorenone derivatives 3a, 3b, 3c/4c, and 3d/4d
A mixture of 2,7-dibromo¯uorene (2.0 g, 6.2 mmol), secundary amine (16.0 mmol), sodium tert-
butoxide (1.7 g, 17.3 mmol), and PdCl2[P(o-tolyl)3]2 (97 mg, 0.12 mmol) in toluene (50 ml) is heated
at 100ꢀC under argon for 6 h. After cooling to room temperature, toluene (50 ml) is added, and the
reaction mixture is washed with water (3Â200 ml), dried over MgSO4, and the solvent is evaporated
on the rotavapor. The oily product is washed with light petroleum ether (20 ml) to remove unreacted
secondary amine. The resulting solid is dissolved in pyridine (30 ml); triton B (2 ml) is added, and

918
J. Ipaktschi and A. Shari®
oxygen is passed through the solution for 1 h. Pyridine is evaporated and the residue is
chromatographed (silica gel; dichloromethane/light petroleum ether, 1/3) to yield the ¯uorenone
derivatives 3a, 3b, 3c/4c, and 3d/4d.
2,7-Bis-(N,N-diphenylamino)-¯uorenone (3a; C37H26N2O)
1.65 g (52%); dark violet crystals; m.p.: 219±220ꢀC; IR (KBr): ꢂ~ ˆ 3030±3060 (aryl-H), 1710
(C=O), 1588 (C=C), 1492, 1465, 1438, 1332, 1314, 1294, 1274, 827, 789, 749, 696, 501 cmꢁ1; UV
(CH2Cl2): ꢁmax (lg") ˆ 244 (4.33), 305 (4.55), 378 (4.43), 553 (3.12) nm; 1H NMR (200 MHz,
CDCl3): ꢃ ˆ 7.0±7.4 (m, aryl-H) ppm; 13C NMR (100 MHz, CDCl3): ꢃ ˆ 119.53, 120.38, 123.50,
124.65, 128.69, 129.48, 135.93, 138.20, 147.27, 148.42, 193.23 (C=O) ppm; MS: m/z (r.I.) ˆ 514
‡
(100) [M ], 257 (96); HRMS: found 514.2014, calcd. 514.2045.
2,7-Dimorpholino¯uorenone (3b; C21H22N2O3)
0.54 g (25%); dark violet crystals; m.p.: 274ꢀC; IR (KBr): ꢂ~ˆ 3050 (aryl-H), 2850±2950
(methylene-H), 1711 (C=O), 1608 (C=C), 1587, 1477, 1445, 1282, 1266, 1238, 1120, 908, 785,
641, 523 cmꢁ1; UV (CH2Cl2): ꢁmax (lg") ˆ 290 (4.54), 344 (4.15), 530 (2.72) nm; 1H NMR
(400 MHz, CDCl3): ꢃ ˆ 3.17 (t, J ˆ 4.8 Hz, 8H, NCH2), 3.85 (t, J ˆ 4.8 Hz, 8H, OCH2), 6.89 (dd,
J ˆ 8.1 Hz, J ˆ 2.4 Hz, 2H, 3-H and 6-H), 7.18 (d, J ˆ 2.4 Hz, 2H, 1-H and 8-H), 7.25 (d, J ˆ 8.1 Hz,
2H, 4-H and 5-H) ppm; 13C NMR (100 MHz, CDCl3): ꢃ ˆ 49.29 (NCH2), 66.70 (OCH2), 111.70,
‡
120.18, 120.58, 135.78, 136.51, 151.38, 194.53 (C=O) ppm; MS: m/z (r.I.) ˆ 350 (100) [M ].
2,7-Di-(N-methyl-N-phenylamino)-¯uorenone (3c; C27H22N2O) and
2-(N-methyl-N-phenylamino)-¯uorenone (4c; C20H15NO)
3c: 1.45 g (60%); dark violet crystals; m.p.: 129ꢀC; IR (KBr): ꢂ~ˆ 3020±3060, (aryl-H), 2945
(methyl-H), 1716 (C=O), 1592 (C=C), 1494, 1476, 1337, 1257, 1112, 834, 784, 758, 706, 695 cmꢁ1
;
1
UV (CH2Cl2): ꢁmax (lg") ˆ 301 (4.56), 360 (4.47), 550 (3.07) nm; H NMR (400 MHz, CDCl3):
ꢃ ˆ 3.32 (s, 6H, CH3), 6.94 (dd, J ˆ 8.1 Hz, J ˆ 2.4 Hz, 2H, 3-H and 6-H), 7.0±7.4 (m, 14H, aryl-H)
ppm; 13C NMR (100 MHz, CDCl3): ꢃ ˆ 40.42 (methyl), 114.64, 120.04, 122.45, 122.87, 123.65,
‡
129.47, 135.70, 136.68, 148.38, 149.04, 194.38 (C=O) ppm; MS: m/z (r.I.) ˆ 390 (69) [M ], 285
‡
(38) [M -C7H7N].
4c: 0.18 g (10%); red crystals; m.p.: 94ꢀC; IR (KBr): ꢂ~ˆ 3020±3060 (aryl-H), 2915 (methyl-H),
1719 (C=O), 1604 (C=C), 1590, 1493, 1458, 1339, 1133, 869, 832, 768, 734, 705 cmꢁ1; UV
(CH2Cl2): ꢁmax (lg") ˆ 252 (4.30), 293 (4.38) 346 (4.12), 501 (2.95) nm; 1H NMR (400 MHz,
CDCl3): ꢃ ˆ 3.35 (s, 3H, CH3), 6.93 (dd, J ˆ 8.2 Hz, 1H, 3-H), 7.0±7.6 (m, 11H, aryl-H) ppm; 13C
NMR (100 MHz, CDCl3): ꢃ ˆ 40.52 (methyl), 113.24, 119.30, 120.99, 122.04, 123.71, 123.80,
124.21, 127.43, 129.64, 134.26, 134.79, 135.05, 135.56, 145.30, 148.12, 150.17, 194.37 (C=O) ppm;
‡
MS: m/z (r.I.) ˆ 285 (100) [M ].
2,7-Bis-(N,N-dibenzylamino)-¯uorenone (3d; C41H34N2O) and 2-(N,N-dibenzylamino)¯uorenone
(4d; C27H21NO)
3d: 1.27 g (36%); blue crystals; m.p.: 220±221ꢀC; IR (KBr): ꢂ~= ˆ 3020±3090 (aryl-H), 2917
(methylene-H), 1705 (C=O), 1611 (C=C), 1583, 1486, 1451, 1383, 1360, 1233, 942, 805, 734 cmꢁ1
;
1
UV (CH2Cl2): ꢁmax (lg") ˆ 298 (4.63), 357 (4.37), 573 (2.80) nm; H NMR (400 MHz, CDCl3):
ꢃ ˆ 4.62 (s, 8H, CH2Ph), 6.63 (dd, J ˆ 8.3 Hz, J ˆ 2.4 Hz, 2H, 3-H and 6-H), 7.0±7.4 (m, 24H, aryl-
H) ppm; 13C NMR (100 MHz, CDCl3): ꢃ ˆ 54.32 (methylene), 109.06, 117.48, 119.89, 126.69,

2,7-Diamino¯uorenones
919
‡
127.06, 128.70, 134.25, 135.85, 138.01, 148.86, 195.27 (C=O) ppm; MS: m/z (r.I.) ˆ 570 (96) [M ],
‡
‡
479 (32) [M -bzl], 387 (23), 311 (19), 283 (12), 91 (100) [bzl ].
4d: 0.14 g (6%); red crystals; m.p.: 140ꢀC; IR (KBr): ꢂ~ˆ 3000±3060 (aryl-H), 2901 (methylene-
H), 1711 (C=O), 1600 (C=C), 1486, 1451, 1360, 1233, 942, 734 cmꢁ1; UV (CH2Cl2): ꢁmax (lg")
1
ˆ 220 (4.10), 240 (3.95), 288 (4.48), 330 (3.99), 343 (3.98), 506 (2.85) nm; H NMR (400 MHz,
CDCl3): ꢃ ˆ 4.68 (s, 4H, CH2Ph), 6.71 (dd, J ˆ 8.3 Hz, J ˆ 2.7 Hz, 1H, 3-H) 7.0±7.6 (m, 16H, aryl-
H) ppm; 13C NMR (100 MHz, CDCl3): 54.44 (methylene), 108.61, 117.18, 118.88, 121.32, 124.10,
126.68, 126.92, 127.18, 128.77, 132.75, 134.31, 134.68, 136.03, 137.76, 145.75, 150.33, 194.48
‡
‡
‡
(C=O) ppm; MS: m/z (r.I.) ˆ 375 (100) [M ], 284 (38) [M -bzl], 91 (93) [bzl ].
2,7-Bis-(N,N-diethylamino)¯uorenone (3e; C21H26N2O) and 2-(N,N-diethylamino)¯uorenone
(4e; C17H17NO)
A solution of 2,7-dibromo¯uorenone (2.0 g, 5.9 mmol), (N,N-diethylamino)tributyltin (6.4 g,
17.7 mmol) and PdCl2[P(o-tolyl)3]2 (140 mg, 0.18 mmol) in toluene (50 ml) is heated at 100ꢀC for
6 h under an argon atmosphere. The solvent is evaporated, and the residue is chromatographed (silica
gel; dichloromethane/light petroleum ether, 1/1) to yield 1.28 g (67%) 3e and 0.18 g (12%) 4e.
3e: Dark green crystals; m.p.: 151±153ꢀC; IR (KBr): ꢂ~ˆ 3060 (aryl-H), 2865±2964 (alkyl-H),
1706 (C=O), 1615 (C=C) , 1579, 1494, 1467, 1443, 1392, 1372, 1362, 1294, 1261, 1195, 1187, 1068,
971, 871, 815, 787 cmꢁ1; UV (CH2Cl2): ꢁmax (lg") ˆ 222 nm (4.01), 298 (4.56), 362 (4.37), 602
(2.81) nm; 1H NMR (400 MHz, CDCl3): ꢃ ˆ 1.17 (t, J ˆ 7.0 Hz, 12H, CH3), 3.35 (q, J ˆ 7.0 Hz, 8H,
CH2), 6.62 (dd, J ˆ 8.2 Hz, J ˆ 2.5 Hz, 2H, 3-H and 6-H), 6.94 (d, J ˆ 2.5 Hz, 2H, 1-H and 8-H), 7.11
(d, J ˆ 8.2 Hz, 2H, 4-H and 5-H) ppm; 13C NMR (100 MHz, CDCl3): ꢃ ˆ 12.72 (CH3), 44.65 (CH2),
108.43, 116.51, 119.80, 133.19, 135.88, 147.28, 196.15 (C=O) ppm; MS: m/z (r.I.) ˆ 311 (100)
‡
‡
‡
[M ], 307 (64) [M -Me], 263 (42) [M -C4H10].
4e: Red crystals; m.p.: 102ꢀC; IR (KBr): ꢂ~ˆ 3050 (aryl-H), 2867±2969 (alkyl-H), 1704 (C=O),
1600 (C=C), 1505, 1456, 1397, 1374, 1357, 1293, 1262, 1196, 1077, 962, 819, 763, 738 cmꢁ1; UV
(CH2Cl2): ꢁmax (lg") ˆ 236 (4.04), 289 (4.52), 348 (4.13), 529 (2.97) nm; 1H NMR (400 MHz,
CDCl3): ꢃ ˆ 1.21 (t, J ˆ 2.5 Hz, 6H, CH3), 3.42 (q, J ˆ 2.5 Hz, 4H, CH2), 6.66 (dd, J ˆ 8.4 Hz,
J ˆ 2.6 Hz, 1H, 3-H), 7.00 (d, J ˆ 2.6 Hz, 1H, 1-H), 7.09 (dt, J ˆ 7.4 Hz, J ˆ 0.8 Hz, 1H, 7-H), 7.28±
7.31 (m, 4-H and 5-H), 7.37 (dt, J ˆ 7.4 Hz, J ˆ 0.8 Hz, 1H, 6-H), 7.54 (d, J ˆ 7.4 Hz, 1H, 8-H) ppm;
13C NMR (100 MHz, CDCl3): 12.68 (CH3), 44.68 (CH2), 107.80, 115.77, 118.71, 121.45, 124.08,
126.54, 130.93, 134.17, 134.77, 136.02, 146.18, 147.74, 195.11 (C=O) ppm; MS: m/z (r.I.) ˆ 251
‡
‡
(25) [M ], 236 (100) [M -Me].
Acknowledgements
We thank the Volkswagenstiftung and the Fonds der Chemischen Industrie for ®nancial
support.
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Received February 11, 1998. Accepted (revised) April 21, 1998