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Synthesis 2010(17): 2926-2930  
DOI: 10.1055/s-0030-1258141
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

An Improved Method for the Synthesis of Carbazolones by Palladium/Copper-Catalyzed Intramolecular Annulation of N-Arylenaminones

Bojie Weng, Rui Liu, Jing-Hua Li*
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. of China
e-Mail: lijh@zjut.edu.cn;

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Publication History

Received 8 January 2010
Publication Date:
30 June 2010 (online)

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Abstract

An improved method for the synthesis of carbazolones via the condensation of arylamines with 1,3-cyclodiketones followed by intramolecular oxidative cyclization catalyzed by palladium acetate and copper acetate in ethanol under an oxygen atmosphere was established. The improved method has the advantage of easily available starting materials and affords good yields.

Key words

carbazolones - intramolecular oxidative cyclization - oxygen - palladium acetate - copper acetate

The carbazolone unit is one of the most abundant heterocycles in natural products and biologically active compounds. Furthermore substituted carbazolones are key intermediates for the synthesis of a variety of carbazole alkaloids [¹a] and drugs, such as serotonin (5-HT3) receptor antagonists (ondansetron and alosetron, Figure  [¹] ), [¹b] [c] murrayaquinone A, koeniginequinone A, and murrayafoline A, [¹d] and other compounds (such as HIV-integrase inhibitor [¹e] and potassium-channel blocker [¹f] ).

Figure 1 Biologically active compounds possessing a carbazolone unit

Thus, various methods have been utilized for the synthesis of carbazolones and their derivatives (Scheme  [¹] ), one of which is the Fischer indole rearrangement using phenylhydrazine and cyclohexane-1,3-dione as starting materials. [²] However, its drawbacks are low yields, harsh conditions, and poor regioselectivities. The palladium- or copper-catalyzed intramolecular cyclization reactions of haloaryl enaminones to give carbazolone derivatives have also been reported, yet the shortcomings of the reactions are high temperature and the use of poisonous ligand, [³a] [d] strong base, [4] and expensive substrates. [³] The oxidation of 2,3,4,9-tetrahydro-1H-carbazole was reported by several groups, however, the unit of carbazole should be synthesized in advance, therefore the scope is largely limited. [5] Söderberg developed a palladium-catalyzed annulation via Stille coupling and reductive N-heterocyclization, nevertheless the procedure is tedious due to unavailable substrates and additives employed. [6] The condensation of arylhydroxylamine with 1,3-diketones for synthesizing carbazolones was also established, however, it suffers from narrow applications. [7]

Scheme 1 Routes to synthesize the carbazolone unit

In 2002, Tietcheu reported a method for the synthesis of carbazolones by using photochemical techniques. [8] Kibayashi developed a direct oxidation of N-arylenaminones; unfortunately, stoichiometric amount of palladium acetate was consumed and yields were quite low. [9] Therefore, there is still a demand to develop a novel and more convenient method for the preparation of carbazolones.

Recently, palladium-catalyzed directly oxidative coupling of two sp² C-H bonds aroused great interest due to its environmentally benign strategy; [¹0] and it has been widely used in homocoupling, [¹¹] cross-coupling, [¹²] and intramolecular coupling. [¹³] Inspired by Kibayashi and Glorius’s work, [¹4] we have developed an efficient method to synthesize carbazolone derivatives via palladium-catalyzed intramolecular oxidative cyclization of arylenaminones, which could be easily prepared under solvent-free conditions in high yields according to our previous work. [¹5]

At first an array of experiments were examined in order to get standard reaction conditions (Scheme  [²] , Table  [¹] ). Initially, the oxidative coupling of N-phenylenaminone 1a as a model substrate in the presence of 0.05 equivalent of Pd(OAc)2 and 0.2 equivalent of Cu(OAc)2˙H2O in refluxing ethanol for 12 hours was tried (Table  [¹] , entry 1). As expected, the desired product was obtained albeit in only 30% yield. The yield was comparably lower when CuBr was used instead of Cu(OAc)2˙H2O (Table  [¹] , entry 2), meanwhile the catalytic combination of other copper salts and H2O2 showed negative effects under the same conditions (Table  [¹] , entries 3-6). Pd2(dba)3 and PdCl2 seemed to be inactive (Table  [¹] , entries 7, 8), which was similar to the replacement of solvents by acetic acid, acetonitrile, dioxane, and DMF (Table  [¹] , entries 9-12). The reaction was slightly promoted by increasing the amount of Cu(OAc)2˙H2O or Pd(OAc)2 (Table  [¹] , entries 13, 14). A satisfactory result was obtained when employing the combination of Pd(OAc)2 (0.15 equiv) and Cu(OAc)2˙H2O (0.4 equiv) as a catalyst under oxygen atmosphere and refluxing in ethanol for 12 hours. Prolonging the reaction time did not improve the efficiency (Table  [¹] , entries 15, 16). This result was remarkably different compared to the recent discovery reported by Jiao, [¹³h] in which the enamine derivatives prepared by condensing aniline and dimethyl butynedioate could be annulated in the presence of palladium under oxygen atmosphere, because in our reaction system no conversion was observed without the use of Cu(OAc)2˙H2O. It might be presumed that electron-withdrawing group such as CO2Et, CO2Me, CN facilitated the annulation process.

Scheme 2 Oxidative coupling of N-phenylenaminone 1a

Table 1 Optimization of the Conditions for the Oxidative Coupling of N-Phenylenaminone 1a a
Entry Catalyst (amount) Oxidant (amount) Solvent Yield (%)b
 1 Pd(OAc)2 (5 mol%) Cu(OAc)2˙H2O (20 mol%) EtOH 30
 2 Pd(OAc)2 (5 mol%) CuBr (20 mol%) EtOH 10
 3 Pd(OAc)2 (5 mol%) CuI (20 mol%) EtOH  0
 4 Pd(OAc)2 (5 mol%) CuCl (20 mol%) EtOH  0
 5 Pd(OAc)2 (5 mol%) Cu(OTf)2 (20 mol%) EtOH trace
 6 Pd(OAc)2 (5 mol%) H2O2 (2 equiv) EtOH  0
 7 Pd2(dba)3 (5 mol%) Cu(OAc)2˙H2O (20 mol%) EtOH  0
 8 PdCl2 (5 mol%) Cu(OAc)2˙H2O (20 mol%) EtOH  0
 9 Pd(OAc)2 (5 mol%) Cu(OAc)2˙H2O (20 mol%) AcOH trace
10 Pd(OAc)2 (5 mol%) Cu(OAc)2˙H2O (20 mol%) MeCN trace
11 Pd(OAc)2 (5 mol%) Cu(OAc)2˙H2O (20 mol%) dioxane tracec
12 Pd(OAc)2 (5 mol%) Cu(OAc)2˙H2O (20 mol%) DMF <5c
13 Pd(OAc)2 (5 mol%) Cu(OAc)2˙H2O (40 mol%) EtOH 35
14 Pd(OAc)2 (10 mol%) Cu(OAc)2˙H2O (40 mol%) EtOH 50
15 Pd(OAc)2 (15 mol%) Cu(OAc)2˙H2O (40 mol%) EtOH 83d
16 Pd(OAc)2 (15 mol%) Cu(OAc)2˙H2O (40 mol%) EtOH 80e
a Reaction conditions: substrate 1a (0.25 mmol), catalyst, oxidant, O2 balloon, prestirred for 5 min at r.t., then refluxed for 12 h.
b Isolated yields.
c Oil bath (80 ˚C).
d No conversion was observed without adding Cu(OAc)2˙H2O (by TLC).
e Reflux, 24 h.

To explore the scope of this catalytic system, a variety of substrates were examined and the corresponding results are listed in Table  [²] . We synthesized a series of intermediates for carbazolones through condensation of different arylamines with cyclohexane-1,3-dione (or 5,5-dimethylcyclohexane-1,3-dione) in the presence of KHSO4 and MgSO4 by grinding them together for 10 minutes and heating at 80 ˚C for 15 minutes. [¹5] [¹6] Carbazolones could be prepared from arylamines and cyclohexane-1,3-diones with simple purification of their corresponding intermediates, by decantation, which were assumed as enaminones (see 1a).

Under the optimized reaction conditions, different functionalized carbazolones were synthesized in good overall yields (Scheme  [³] , Table  [²] , entries 1-16). This reaction tolerates several functional groups, such as methoxy, methyl­, chloro, and bromo, at different positions of the aro­matic ring. Similarly, naphthylenaminone also exhibited satisfactory activity under the same catalytic system with good yield and high regioselectivity (Table  [²] , entry 11). Unfortunately, when the aromatic ring bearing the 4-nitro group was used as a substrate, the desired product could not be obtained (Table  [²] , entry 17), and the intermediate, 3-(4-nitrophenylamino)cyclohex-2-enone (1q) was obtained in 85% yield after recrystallization. The reason of this phenomenon might be due to inactivation of aryl­amine caused by nitro group.

Scheme 3 Synthesis of a series of functional carbazolones

Table 2 Compounds 2 Prepared via N-Arylenaminonesa
Entry X2 R¹ Yield of 2 (%)b
 1 H,H H 2a, 71
 2 H,H 3-MeO 2b, 68
 3 H,H 3-Me 2c, 50
 4 H,H 3-Br 2d, 60
 5 H,H 1-Me 2e, 77
 6 H,H 1-Cl 2f, 74
 7 H,H 3-Cl 2g, 48
 8 Me,Me H 2h, 71
 9 Me,Me 3-MeO 2i, 62
10 Me,Me 3-Me 2j, 68
11 Me,Me 3,4-CH=CHCH=CHc 2k, 47
12 Me,Me 1-Me 2l, 54
13 Me,Me 1-Cl 2m, 61
14 Me,Me 3-Cl 2n, 47
15 Me,Me 3-Br 2o, 50
16 Me,Me 2,4-Me2 2p, 70
17d H,H 4-O2N 2q, 0
a Arylamine (5 mmol), 1,3-diketones (5 mmol), KHSO4 (1 g), and MgSO4 (1 g), were ground together for 10 min at r.t., then were kept at 80 ˚C for 15 min.
b Isolated yields. The overall yields of 2 were enhanced approximately 3-4% by further recrystallization of the intermediates before proceeding oxidative couplings.
c Caution! Starting material β-naphthylamine is carcinogenic. d Intermediate 1q was isolated in 85% yield.

It has been reported recently that N-arylenaminones are prone to react with electrophiles at the α-C position. [¹7] The mechanism may be assumed to involve three steps: (a) an electrophilic palladation of the nucleophilic enamine; (b) ortho CH activation for the formation of the six-membered­-ring transition state containing palladium; (c) reductive elimination generating the carbazolones with liberation of active palladium(0) species (Scheme  [4] ). The regenerated palladium(0) complex is oxidized to the palladium(II) species by Cu(OAc)2˙H2O and oxygen to complete the whole catalytic cycle.

Scheme 4 Possible mechanism for synthesis of carbazolones

In conclusion, an improved method for the synthesis of carbazolones from available arylamines and 1,3-cyclodiketones via intramolecular oxidative cyclization catalyzed by palladium acetate and copper acetate under oxygen atmosphere in ethanol, which is environmentally friendly and effective, has been developed. Further studies on the synthesis of the functionalized carbazolones and their applications are currently in progress in our laboratory.

All reactions were carried out by standard Schlenk technique and run under an O2 atmosphere. All the substrates and bases were commercially available. All products were confirmed by ¹H NMR, ¹³C NMR spectra recorded on Bruker Avance III spectrometer (500 MHz for ¹H NMR, 125 MHz for ¹³C NMR). Melting points were obtained using a precision X-4 digital display apparatus from Tektronix Instrument Co., Ltd. Beijing and are uncorrected. Petroleum ether (PE) refers to the fraction boiling in the range 60-90 ˚C.

2,3-Dihydro-1 H -carbazol-4(9 H )-one (2a); [³-6] Typical Procedure

A mixture of the cyclohexane-1,3-dione (560 mg, 5 mmol), aniline (484 mg, 5.2 mmol) and KHSO4/MgSO4 (1 g, weight ratio 1:1) was ground in a mortar for 10 min at r.t., and then kept for 15 min in an oil bath at 80 ˚C. The reaction mixture was extracted with MeOH (20 mL). The filtrate was concentrated under reduced pressure to give a solid, which was dissolved in 95% hot EtOH and then cooled to r.t. The liquid was removed by decantation from the precipitated enaminone 1a, which was used directly in the next step. The precipitated 1a was mixed with Cu(OAc)2˙H2O (400 mg, 0.4 equiv) and Pd(OAc)2 (168 mg, 0.15 equiv) in EtOH (20 mL). The mixture was stirred with a magnetic stir bar for 5 min at r.t., then refluxed for 12 h under O2 atmosphere by using an O2 balloon. After the completion of the reaction, the mixture was purified by column chromatography on silica gel (100-200 mesh) with petroleum ether and EtOAc (1:2) as eluent to give the pure product 2a; overall yield: 164 mg (71%); mp 218-221 ˚C; R f  = 0.30 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 11.85 (s, 1 H), 7.96 (d, J = 7 Hz, 1 H), 7.40 (d, J = 7 Hz, 1 H), 7.12-7.18 (m, 2 H), 2.96 (t, J = 6 Hz, 2 H), 2.43 (t, J = 6 Hz, 2 H), 2.10-2.14 (m, 2 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.9, 152.3, 135.9, 124.5, 122.4, 121.5, 120.2, 111.8, 111.5, 37.8, 23.4, 22.7.

6-Methoxy-2,3-dihydro-1 H -carbazol-4(9 H )-one (2b) [¹8]

Yield: 68%; mp 250-254 ˚C; R f  = 0.45 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 11.72 (s, 1 H), 7.46 (s, 1 H), 7.29 (d, J = 8.5 Hz, 1 H), 6.79 (d, J = 7 Hz, 1 H), 3.77 (s, 3 H), 2.94 (t, J = 5.5 Hz, 2 H), 2.42 (t, J = 5.5 Hz, 2 H), 2.10 (t, J = 5.5 Hz, 2 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.8, 155.2, 152.4, 130.6, 125.3, 112.2, 117.7, 111.6, 102.6, 55.3, 37.8, 23.4, 22.8.

6-Methyl-2,3-dihydro-1 H -carbazol-4(9 H )-one (2c) [³c]

Yield: 50%; mp 252-256 ˚C; R f  = 0.54 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 11.73 (s, 1 H), 7.77 (s, 1 H), 7.27 (d, J = 8 Hz, 1 H), 6.98 (d, J = 8 Hz, 1H), 2.94 (t, J = 5 Hz, 2 H), 2.41 (t, J = 6 Hz, 2 H), 2.38 (s, 3 H), 2.11 (t, J = 6 Hz, 2 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.7, 152.1, 134.1, 130.2, 124.8, 123.7, 120.1, 111.4, 111.1, 37.8, 23.4, 22.7, 21.2.

6-Bromo-2,3-dihydro-1 H -carbazol-4(9 H )-one (2d) [³c]

Yield: 60%; mp >270 ˚C; R f  = 0.35 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 12.06 (s, 1 H), 8.06 (s, 1 H), 7.38 (d, J = 8 Hz, 1 H), 7.30 (d, J = 8 Hz, 1 H), 2.97 (s, 2 H), 2.43 (s, 2 H), 2.12 (s, 2 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.9, 153.5, 134.7, 126.2, 124.9, 122.2, 114.1, 113.6, 111.2, 37.6, 23.2, 22.7.

8-Methyl-2,3-dihydro-1 H -carbazol-4(9 H )-one (2e) [6a]

Yield: 77%; mp >280 ˚C; R f  = 0.53 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 11.75 (s, 1 H), 7.78 (d, J = 7.5 Hz, 1 H), 6.95-7.05 (m, 2 H), 2.98 (s, 2 H), 2.47 (s, 3 H), 2.42 (s, 2 H), 2.12-2.13 (m, 2 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.9, 152.0, 135.2, 124.2, 123.1, 121.6, 120.7, 117.7, 112.1, 37.8, 23.4, 22.7, 16.6.

8-Chloro-2,3-dihydro-1 H -carbazol-4(9 H )-one (2f) [¹9]

Yield: 74%; mp 279-282 ˚C; R f  = 0.49 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 12.19 (s, 1 H), 7.91 (d, J = 8 Hz, 1 H), 7.25 (d, J = 8 Hz, 1 H), 7.15 (t, J = 8 Hz, 1 H), 3.00 (t, J = 6 Hz, 2 H), 2.45 (t, J = 6 Hz, 2 H), 2.11-2.16 (m, 2 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 193.1, 153.5, 132.8, 126.3, 122.7, 122.0, 119.0, 115.9, 112.5, 37.7, 23.2, 22.7.

6-Chloro-2,3-dihydro-1 H -carbazol-4(9 H )-one (2g) [³c]

Yield: 48%; mp 271-276 ˚C; R f  = 0.48 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 12.05 (s, 1 H), 7.90 (s, 1 H), 7.43 (d, J = 8.5 Hz, 1 H), 7.19 (d, J = 7.5 Hz, 1 H), 2.97 (t, J = 6 Hz, 2 H), 2.44 (t, J = 6 Hz, 2 H), 2.13 (t, J = 6 Hz, 2 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.9, 153.6, 134.4, 126.1, 125.6, 122.3, 119.2, 113.1, 111.4, 37.6, 23.2, 22.7.

2,2-Dimethyl-2,3-dihydro-1 H -carbazol-4(9 H )-one (2h) [³e]

Yield: 71%; mp 189-193 ˚C; R f = 0.60 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 11.83 (s, 1 H), 7.93 (m 1 H), 7.39 (m, 1 H), 7.15 (m, 2 H), 2.85 (s, 2 H), 2.33 (s, 2 H), 1.09 (s, 6 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.1, 151.0, 136.2, 124.3, 122.3, 121.5, 120.0, 111.6, 110.5, 51.9, 36.4, 35.3, 28.2.

6-Methoxy-2,2-dimethyl-2,3-dihydro-1 H -carbazol-4(9 H )-one (2i) [¹8]

Yield: 62%; mp 240 ˚C; R f  = 0.59 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 11.71 (s, 1 H), 7.45 (d, J = 2.5 Hz, 1 H), 7.29 (d, J = 8.5 Hz, 1 H), 6.78 (m, 1 H), 3.77 (s, 3 H), 2.82 (s, 2 H), 2.31 (s, 2 H), 1.08 (s, 6 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.1, 155.2, 151.1, 130.9, 125.1, 112.3, 111.5, 110.5, 102.4, 55.3, 51.9, 36.4, 35.2, 28.2.

2,2,6-Trimethyl-2,3-dihydro-1 H -carbazol-4(9 H )-one (2j) [¹8]

Yield: 68%; mp 273-275 ˚C; R f  = 0.63 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 11.71 (s, 1 H), 7.7 (s, 1 H), 7.27 (d, J = 8.5 Hz, 1 H), 6.98-6.96 (m, 1 H), 2.82 (s, 2 H), 2.38 (s, 3 H), 2.31 (s, 2 H), 1.08 (s, 6 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.0, 150.9, 134.4, 130.3, 124.6, 123.5, 120.0, 111.2, 110.1, 51.9, 36.4, 35.2, 28.2, 21.2.

9,9-Dimethyl-9,10-dihydro-7 H -benzo[ c ]carbazol-11(8 H )-one (2k) [²0]

Yield: 47%; mp 250-254 ˚C; R f  = 0.80 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 12.28 (s, 1 H), 9.83 (d, J = 8.5 Hz, 1 H), 7.92 (d, J = 8 Hz, 1 H), 7.69 (d, J = 8.5 Hz, 1 H), 7.60 (d, J = 8.5 Hz, 1 H), 7.53 (m, 1 H), 7.42 (m, 1 H), 2.95 (s, 2 H), 2.49 (s, 2 H), 1.12 (s, 6 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.0, 149.5, 133.2, 130.0, 128.1, 128.1, 127.4, 125.0, 123.9, 123.7, 119.6, 113.5, 113.0, 53.1, 36.9, 34.7, 27.9.

2,2,8-Trimethyl-2,3-dihydro-1 H -carbazol-4(9 H )-one (2l) [¹8]

Yield: 54%; mp 255-257 ˚C; R f  = 0.60 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 11.72 (s, 1 H), 7.76 (d, J = 7.5 Hz, 1 H), 7.04 (t, J = 7.5 Hz, 1 H), 6.96 (d, J = 7.5 Hz, 1 H), 2.86 (s, 2 H), 2.47 (s, 3 H), 2.32 (s, 2 H), 1.09 (s, 6 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.2, 150.8, 135.6, 124.0, 122.9, 121.6, 120.8, 117.6, 110.8, 51.9, 36.4, 35.2, 28.2, 16.7.

8-Chloro-2,2-dimethyl-2,3-dihydro-1 H -carbazol-4(9 H )-one (2m)

Yield: 61%; mp 210-213 ˚C; R f  = 0.75 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 12.17 (s, 1 H), 7.90 (d, J = 8.0 Hz, 1 H), 7.25 (d, J = 8 Hz, 1 H), 7.15 (t, J = 8 Hz, 1 H), 2.89 (s, 2 H), 2.36 (s, 2 H), 1.09 (s, 6 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.4, 152.2, 133.2, 126.2, 122.7, 121.9, 118.9, 116.0, 111.3, 51.8, 36.3, 35.2, 28.1.

6-Chloro-2,2-dimethyl-2,3-dihydro-1 H -carbazol-4(9 H )-one (2n) [7]

Yield: 47%; mp 278 ˚C; R f  = 0.65 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 12.03 (s, 1 H), 7.87 (d, J = 1.5 Hz, 1 H), 7.42 (d, J = 8.5 Hz, 1 H), 7.18 (m, 1 H), 2.86 (s, 2 H), 2.34 (s, 2 H), 1.08 (s, 6 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.2, 152.4, 134.7, 126.1, 125.4, 122.2, 119.1, 113.2, 110.1, 51.7, 36.3, 35.2, 28.1.

6-Bromo-2,2-dimethyl-2,3-dihydro-1 H -carbazol-4(9 H )-one (2o)

Yield: 50%; mp >270 ˚C; R f  = 0.65 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 12.03 (s, 1 H), 8.03 (s, 1 H), 7.38 (d, J = 8.0 Hz, 1 H), 7.30 (d, J = 8.0 Hz, 1 H), 2.86 (s, 2 H), 2.34 (s, 2 H), 1.08 (s, 6 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 192.2, 152.2, 135.0, 126.0, 124.8, 122.1, 114.1, 113.7, 110.0, 51.7, 36.2, 35.2, 28.1.

2,2,5,7-Tetramethyl-2,3-dihydro-1 H -carbazol-4(9 H )-one (2p) [²¹]

Yield: 70%; mp 247-250 ˚C; R f  = 0.81 (PE-EtOAc, 1:1).

¹H NMR (500 MHz, DMSO-d 6/TMS): δ = 11.66 (s, 1 H), 6.96 (s, 1 H), 6.71 (s, 1 H), 2.80 (s, 2 H), 2.76 (s, 3 H), 2.32 (s, 5 H), 1.07 (s, 6 H).

¹³C NMR (125 MHz, DMSO-d 6/TMS): δ = 190.8, 150.7, 137.2, 131.6, 130.6, 124.7, 121.8, 111.6, 108.8, 53.0, 36.8, 34.5, 28.0, 22.4, 20.9.

5,5-Dimethyl-3-(4-nitrophenylamino)cyclohex-2-enone (1q) [¹5]

Yield: 85%; mp 176-178 ˚C; R f  = 0.30 (PE-EtOAc-Et3N, 1:3:0.1).

¹H NMR (500 MHz, CDCl3/TMS): δ = 2.07-2.11 (m, 2 H), 2.42 (t, J = 7 Hz, 2 H), 2.57 (t, J = 6 Hz, 2 H), 5.85 (s, 1 H), 6.83 (br, 1 H, NH), 7.26 (m, 2 H), 8.20 (d, J = 9 Hz, 2 H).

¹³C NMR (125 MHz, CDCl3/TMS): δ = 198.9, 159.9, 144.9, 143.3, 125.3, 121.3, 103.1, 36.6, 29.8, 21.7.

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Figure 1 Biologically active compounds possessing a carbazolone unit

Scheme 1 Routes to synthesize the carbazolone unit

Scheme 2 Oxidative coupling of N-phenylenaminone 1a

Scheme 3 Synthesis of a series of functional carbazolones

Scheme 4 Possible mechanism for synthesis of carbazolones