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Synthesis 2010(6): 923-928  
DOI: 10.1055/s-0029-1218634
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Azapyrrolo[3,2,1-jk]carbazoles, Azaindolo[3,2,1-jk]carbazoles, and Carbazole-1-carbonitriles by Gas-Phase Cyclization of Aryl Radicals

Lynne A. Crawford, Hamish McNab*, Andrew R. Mount, Jeanne Verhille, Stuart I. Wharton
School of Chemistry, The University of Edinburgh, West Mains Road, Edinburgh, EH9 3JJ, UK
Fax: +44(131)6504743; e-Mail: H.McNab@ed.ac.uk;

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Publication History

Received 9 October 2009
Publication Date:
08 January 2010 (online)

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Abstract

Flash vacuum pyrolysis of N-(2-nitroheteroaryl)indoles or -carbazoles at 875 ˚C gave aza analogues of strained pyrrolo[3,2,1-jk]carbazole (50-55%) and indolo[3,2,1-jk]carbazole (55-85%) ring systems, respectively, through generation of aryl radicals and cyclization. The corresponding reactions of N-(2-nitroheteroaryl)indazoles and -benzimidazoles at 850 ˚C, on the other hand, gave carbazole-1-carbonitrile derivatives (56-64%) by a mechanism involving radical ring opening and hydrogen atom rearrangement.

Key words

gas-phase reactions - cyclizations - heterocycles - pyro­lysis - nitro compounds

In previous papers, [¹] [²] we have shown that flash vacuum pyrolysis (FVP) of aromatic nitro compounds provides aryl radical intermediates that, in appropriate frameworks, cyclize efficiently to provide the strained pyrrolo[3,2,1-jk]carbazole 1 or indolo[3,2,1-jk]carbazole 2 ring systems (Figure  [¹] ) in just two steps from commercially available starting materials.

Figure 1

Because the indolo[3,2,1-jk]carbazoles 2, in particular, show interesting properties under electrooxidation conditions, [²] we examined the effects on the ring synthesis of nitrogen atoms at various positions in the five- and six-membered rings of the precursors. When the heteroatom is present in a six-membered ring, the method provides useful synthetic routes to azapyrrolo[3,2,1-jk]carbazoles and azaindolo[3,2,1-jk]carbazoles. When a second heteroatom is present in the five-membered ring, ring opening and rearrangement take place under the FVP conditions to give carbazole-1-carbonitriles regiospecifically.

SNAr reactions of N-heterocyclic nucleophiles with carbonate bases in dipolar aprotic solvents are well known. [¹-³] However, the reactions of indole 3, carbazole 8, or 9H-pyrido[2,3-b]indole (9; α-carboline) with chloro(nitro)pyridines 4 or 5 required individual optimization because of the poor reactivity of the nucleophile and the sensitivity of the halo compound; details are given in the experimental section. In general, the most effective base was cesium carbonate, and anhydrous dimethyl sulfoxide or acetonitrile was the optimal solvent. Yields of products 6, 7, and 10-12 varied from 50 to 80% after chromatography (Scheme  [¹] ). At a late stage in the project, the use of palladium-catalyzed coupling [4] was studied for one case, and this proved to be at least as efficient as the SNAr methods. Reactions of benzimidazole 13 or indazole 14 with 1-fluoro­-2-nitrobenzene (15) at 125 ˚C in N,N-dimethyl­form­amide provided the nitroaryl derivatives 16 and 17 in yields of 81 and 57%, respectively (Scheme  [¹] ).

Scheme 1

FVP of the nitro derivatives 6, 7, and 10-12 took place cleanly at 875 ˚C to provide the parent azapyrrolo[3,2,1-jk]carbazoles 18-19 (50-55%) and azaindolo[3,2,1-jk]carbazoles 20-22 (55-85%), all of which are new heterocyclic systems (Scheme  [²] ). Because of the reactivity of the nitrogen oxide byproducts, some modifications to the normal FVP trapping systems were required, [¹] [²] and these are described in the experimental section. Therefore, the increased strain in the azapyrrolo[3,2,1-jk]carbazole and azaindolo[3,2,1-jk]carbazole systems compared with 1 and 2, which is the result of the presence of short C-N bonds in the six-membered ring(s), can clearly be accommodated, and the systems are stable even at 875 ˚C.

Scheme 2

In contrast, FVP at 850 ˚C of the parent benzimidazole 16 and indazole 17 both gave carbazole-1-carbonitrile (25) (57% and 64%, respectively) as the sole product that was obtained in a significant yield. It is likely that the imidazolocarbazole (23) and the pyrazolocarbazole (24) are formed as intermediates, but these are too strained to survive the pyrolysis temperatures needed to break the C-NO2 bond. Radical cleavage of the five-membered ring followed by hydrogen transfer gives the carbazole. In the benzimidazole series, the initial formation of an isocyanide may be followed by thermal rearrangement to the nitrile (Scheme  [³] ), [5] although rearrangement at the imidoyl radical stage is also possible.

Scheme 3

To explore the synthetic utility of this regiospecific route to carbazole-1-carbonitriles, we briefly studied the FVP reactions of the substituted benzimidazole precursors 26-29 (made by the method shown in Scheme  [¹] ). The sites of the substituents on the benzimidazole were chosen to avoid regiochemical problems at the arylation stage; those on the aryl ring (including the heteroatom) were chosen to avoid similar problems due to hydrogen atom rearrangements at the aryl radical stage. [6] In each case, the corresponding substituted carbazole-1-carbonitrile 30-33 was obtained as the major product. Carbazole-1-carbonitriles are relatively uncommon, and this synthetic route complements those involving stepwise functional group interconversions, [7] cycloaddition reactions, [8] or Friedel-Crafts-type processes. [9]

Scheme 4

In conclusion, the parent members of new azapyrrolo[3,2,1-jk]carbazole and azaindolo[3,2,1-jk]carbazole ring systems have been made by FVP of nitro-substituted pyridinylcarbazoles and -indoles. These results provide further examples of the effectiveness of this strategy for the formation of strained rings. In contrast to the thermal stability of these systems, the five-membered rings of 23 and 24 cleaved under the conditions required for their formation. Nevertheless, such reactions provide regio­specific routes to a range of carbazole-1-carbonitrile derivatives.

¹H and ¹³C NMR spectra were recorded on a Bruker ARX250 spectrometer operating at 250 MHz and 63 MHz respectively. Chemical shifts are given in ppm relative to TMS. Mass spectra were recorded on a Kratos MS50 instrument under electron impact conditions, unless stated otherwise. All solvents were dried over molecular sieves. Starting materials were purchased from Aldrich. Melting points were recorded on a Gallenkamp apparatus and are uncorrected.

N- Arylation Reactions

Method 1: The indole (3) or carbazole (8) (6 mmol) and a chloronitropyridine (0.95 g, 6 mmol) were dissolved in dry DMSO (20 mL). Cs2CO3 (2.15 g, 6.6 mmol) was added to the soln with stirring. The suspension was stirred for 18 h at 100 ˚C then cooled and diluted with brine (50 mL). The mixture was extracted with CH2Cl2 (4 × 100 mL) and the organic layers were combined and washed with H2O (2 × 100 mL) then dried (MgSO4). The solvent was removed under reduced pressure and the residue was pre-adsorbed onto silica gel. The product was purified by dry flash chromatography (hexane-EtOAc).

Method 2: Carbazole (8) (0.500 g, 3.0 mmol), a chloronitropyridine 4 or 5 (0.475 g, 3.0 mmol), and K2CO3 (8.270 g, 60.00 mmol) were weighed and mixed. A soln of Pd(OAc)2 (0.027 g, 4 mol%) and rac-BINAP (0.075 g, 4 mol%) in toluene (10 mL) was stirred for 10 min under argon and then added to the pyridine-carbazole mixture under argon. The remainder of the catalyst mix was washed into the reaction mixture with toluene (15 mL). The mixture was refluxed for 24 h, then cooled to r.t., diluted with CH2Cl2, and washed with H2O (2 × 50 mL). The extracts were filtered through a pad of Celite and then dried (MgSO4). The soln was concentrated onto silica gel for purification by dry flash chromatography (hexane-EtOAc).

Method 3: The carbazole or indole (6.3 mmol) and a chloronitropyridine 4 or 5 (1.50 g, 9.5 mmol) were dissolved in MeCN (30 mL), and Cs2CO3 (2.50 g, 7.7 mmol) was added to the soln with stirring. The suspension was stirred for 30 h at reflux, the MeCN was concentrated under reduced pressure, and the residue was redissolved in EtOH. This soln was pre-adsorbed onto silica gel for separation by dry flash chromatography (hexane-EtOAc).

Method 4: The appropriate benzimidazole or indazole (10 mmol), K2CO3 (10.2 mmol), and the appropriate 1-fluoro-2-nitrobenzene (10 mmol) were heated at 125 ˚C in DMF (30 mL) for 8 h. H2O (100 mL) was added to the cooled soln, which was extracted with Et2O (3 × 100 mL). The combined organic fractions were washed with H2O (3 × 100 mL), dried (MgSO4), and concentrated under reduced pressure.

1-(3-Nitropyridin-2-yl)-1 H -indole (6)

Prepared by Method 1 from indole (3; 1.05 g, 9.0 mmol) and 2-chloro-3-nitropyridine (4; 1.56 g, 9.9 mmol); yield: 1.72 g (80%); mp 110-111 ˚C.

¹H NMR (CDCl3): δ = 8.64 (dd, ³ J = 4.7 Hz, 4 J = 1.7 Hz, 1 H), 8.23 (dd, ³ J = 8.1 Hz, 4 J = 1.7 Hz, 1 H), 7.57 (m, 1 H), 7.40 (m, 1 H), 7.28-7.10 (m, 4 H), 6.67 (d, ³ J = 3.5 Hz, 1 H).

¹³C NMR (CDCl3): δ = 152.31 (CH), 144.27 (Cq), 139.18 (Cq), 135.06 (Cq), 134.70 (CH), 129.81 (Cq), 126.37 (CH), 123.46 (CH), 121.93 (CH), 121.32 (CH), 121.20 (CH), 118.81 (CH), 107.09 (CH).

MS: m/z (%) = 239 (100) [M+], 181 (42), 154 (14), 89 (16), 63 (17).

HRMS: m/z [M+] calcd for C13H9N3O2: 239.0821; found: 239.0822.

1-(3-Nitropyridin-4-yl)-1 H -indole (7)

Prepared by Method 3 from indole (3; 1.05 g, 9.0 mmol), 4-chloro-3-nitropyridine (5) (1.56 g, 9.9 mmol), and Cs2CO3 (3.51 g, 10.76 mmol); yield: 1.51 g (70%); mp 117-118 ˚C.

¹H NMR (CDCl3): δ = 9.40 (s, 1 H), 9.03 (d, ³ J = 5.4 Hz, 1 H), 7.85 (m, 1 H), 7.75 (d, ³ J = 5.4 Hz, 1 H), 7.45-7.35 (m, 3 H), 7.28 (d, ³ J = 3.5 Hz, 1 H), 6.97 (d, ³ J = 3.5 Hz, 1 H).

¹³C NMR (CDCl3): δ = 154.18 (CH), 147.28 (CH), 140.58 (Cq), 139.93 (Cq), 135.12 (Cq), 129.63 (Cq), 126.62 (CH), 123.72 (CH), 122.06 (CH), 121.73 (CH), 121.50 (CH), 109.47 (CH), 107.49 (CH).

MS: m/z (%) = 239 (100) [M+], 194 (97), 166 (35), 154 (35), 139 (46), 89 (49), 63 (37).

Anal. Calcd for C13H9N3O2: C, 65.3; H, 3.8; N, 17.6. Found: C, 65.75; H, 3.7; N, 17.15.

9-(3-Nitropyridin-2-yl)-9 H -carbazole (10)

Prepared by Method 1 by using carbazole (8; 1.00 g, 6 mmol) and 2-chloro-3-nitropyridine (4; 0.95 g, 6 mmol); yield: 0.87-1.04 g (50-60%); mp 143-144 ˚C.

Application of Method 2 also gave 10; yield: 0.649 g (75%); mp 144-145 ˚C. In practice, the product was easier to purify by using Method 2 than by Method 1.

¹H NMR (DMSO-d 6): δ = 9.06 (dd, ³ J = 4.7 Hz, 4 J = 1.7 Hz, 1 H), 8.82 (dd, ³ J = 8.2 Hz, 4 J = 1.6 Hz, 2 H), 8.27 (m, 1 H), 7.90 (dd, ³ J = 8.2 Hz, ³ J = 4.8 Hz, 1 H), 7.49-7.33 (m, 6 H).

¹³C NMR (DMSO-d 6): δ = 154.10 (CH), 142.48 (Cq), 141.78 (Cq), 139.09 (2 Cq), 136.24 (CH), 126.69 (2 CH), 124.52 (CH), 123.69 (2 Cq), 121.56 (2 CH), 120.83 (2 CH), 110.07 (2 CH).

MS: m/z (%) = 289 (100) [M+], 242 (89), 215 (15), 189 (5), 167 (19), 140 (6), 121 (26).

Anal. Calcd for C17H11N3O2: C, 70.6; H, 3.8; N, 14.55. Found: C, 70.85; H, 3.9; N, 14.5.

9-(3-Nitropyridin-4-yl)-9 H -carbazole (11)

Prepared by Method 3 from carbazole (8; 1.05 g, 6.29 mmol) and 4-chloro-3-nitropyridine (5; 1.50 g, 9.46 mmol); yield: 1.45 g (80%); mp 181-182 ˚C, after chromatography.

¹H NMR (DMSO-d 6): δ = 9.50 (s, 1 H), 9.16 (d, ³ J = 5.3 Hz, 1 H), 8.30 (d, ³ J = 7.6 Hz, 1 H), 8.11 (d, ³ J = 5.3 Hz, 1 H), 7.51-7.32 (m, 7 H).

¹³C NMR (DMSO-d 6): δ = 156.03 (CH), 147.04 (CH), 141.97 (Cq), 139.12 (2 Cq), 137.81 (Cq), 126.89 (2 CH), 124.73 (CH), 123.75 (2 Cq), 121.61 (2 CH), 121.00 (2 CH), 109.45 (2 CH).

MS: m/z (%) = 289 (100) [M+], 242 (52), 215 (24), 140 (5), 107 (23).

Anal. Calcd for C17H11N3O2: C, 70.6; H, 3.8; N, 14.55. Found: C, 71.15; H, 3.95; N, 14.4.

9-(3-Nitropyridin-2-yl)-9 H -pyrido[2,3- b ]indole (12)

9H-Pyrido[2,3-b]indole (9, α-carboline; 0.328 g, 1.96 mmol) and 2-chloro-3-nitropyridine (4; 0.464 g, 6 mmol) were dissolved in dry DMF (10 mL). Cs2CO3 (0.763 g, 2.34 mmol) was added to the soln with stirring. The suspension was stirred for 18 h at 125 ˚C before being cooled and diluted with brine (50 mL). The suspension that formed was extracted with CH2Cl2 (4 × 50 mL). The CH2Cl2 layers were combined, washed with H2O (2 × 50 mL), and dried (MgSO4). The CH2Cl2 soln was pre-adsorbed onto silica gel for separation by dry flash chromatography (hexane-EtOAc) to give 12; yield: 0.209 g (37%); mp 167-169 ˚C.

¹H NMR (DMSO-d 6): δ = 8.79 (dd, ³ J = 6.4 Hz, 4 J = 1.7 Hz, 1 H), 8.47 (dd, ³ J = 8.1 Hz, 4 J = 1.7 Hz, 1 H), 8.28-8.23 (m, 2 H), 8.01 (dq, ³ J = 7.8 Hz, 4 J = 1.5 Hz, 5 J = 0.7 Hz, 1 H), 7.88 (dq, ³ J = 8.1 Hz, 4 J = 1.7 Hz, 5 J = 0.8 Hz, 1 H), 7.51-7.39 (m, 2 H), 7.32 (td, ³ J = 7.7 Hz, 4 J = 1.1 Hz, 1 H), 7.17 (dd, ³ J = 7.5 Hz, ³ J = 4.5 Hz, 1 H).

¹³C NMR (DMSO-d 6): δ = 155.48 (Cq), 152.17 (CH), 150.35 (Cq), 145.81 (CH), 142.72 (Cq), 138.00 (Cq), 134.64 (CH), 128.53 (CH), 127.46 (CH), 122.31 (CH), 122.22 (Cq), 122.05 (CH), 120.90 (CH), 117.61 (CH), 117.43 (Cq), 112.33 (CH).

MS: m/z (%) = 290 (3) [M+], 190 (100), 168 (48), 155 (71), 128 (13), 78 (7).

HRMS: m/z [M+] calcd for C16H10N4O2: 290.0804; found: 290.0802.

1-(2-Nitrophenyl)-1 H -benzimidazole (16)

Application of Method 4 gave 16; yield; 1.94 g (81%); mp 80-81 ˚C (Lit. [¹0] 80-82 ˚C).

¹H NMR (CDCl3): δ = 8.14 (dd, ³ J = 8.0 Hz, 4 J = 1.6 Hz, 1 H), 8.01 (s, 1 H), 7.54-7.89 (m, 4 H), 7.10-7.38 (m, 3 H).

¹³C NMR (CDCl3): δ = 145.97 (Cq), 143.23 (Cq), 142.32 (CH), 134.17 (CH), 129.90 (CH), 129.62 (CH), 129.27 (Cq), 125.84 (CH), 124.09 (CH), 123.07 (CH), 120.66 (CH), 109.32 (CH) (one Cq not apparent).

MS: m/z (%) = 239 (61) [M+], 222 (7), 192 (23), 181 (60), 140 (17), 77 (20).

1-(2-Nitrophenyl)-1 H -indazole (17)

Application of Method 4 gave 17; yield; 1.37 g (57%); mp 151-152 ˚C [Lit. [¹¹] 152-153 ˚C].

¹H NMR (CDCl3): δ = 8.22 (s, 1 H), 7.22-8.03 (m, 8 H).

¹³C NMR (CDCl3): δ = 142.85 (Cq), 139.45 (Cq), 136.89 (CH), 133.14 (CH), 132.72 (Cq), 128.16 (CH), 127.66 (CH), 127.15 (CH), 125.53 (CH), 124.95 (Cq), 122.02 (CH), 121.49 (CH), 109.19 (CH).

MS: m/z (%) = 239 (100) [M+], 222 (86), 192 (54), 166 (49), 140 (37), 118 (63), 91 (50), 77 (60).

5,6-Dimethyl-1-(2-nitrophenyl)-1 H -benzimidazole (26)

Application of Method 4 gave 26; yield: 2.54 g (>95%); mp 155 ˚C.

¹H NMR (CDCl3): δ = 8.13 (dd, ³ J = 7.9 Hz, 4 J = 1.4 Hz, 1 H), 7.90 (s, 1 H), 7.81 (td, ³ J = 7.6 Hz, 4 J = 1.4 Hz, 1 H), 7.68 (ddd, ³ J = 7,9, 7.6 Hz, 4 J = 1.4 Hz, 1 H), 7.63 (s, 1 H), 7.56 (dd, ³ J = 7.6 Hz, 4 J = 1.4 Hz, 1 H), 6.91 (s, 1 H), 2.38 (s, 3 H), 2.32 (s, 3 H).

¹³C NMR (CDCl3): δ = 146.20 (Cq), 142.34 (Cq), 142.00 (CH), 134.61 (CH), 133.94 (Cq), 133.27 (Cq), 132.59 (Cq), 130.14 (CH), 130.06 (CH), 126.28 (CH), 121.14 (CH), 109.96 (CH), 20.94 (CH3), 20.63 (CH3) (one Cq not apparent).

MS: m/z (%) = 267 (41) [M+], 255 (100), 254 (82), 209 (25), 73 (97), 43 (96).

HRMS: m/z [M+] calcd for C15H13N3O2: 267.10023; found: 267.10043.

1-(4-Methyl-2-nitrophenyl)-1 H -benzimidazole (27)

Application of Method 4 on a 3.3 mmol scale gave 27; yield: 0.81 g (95%), mp 96 ˚C.

¹H NMR (CDCl3): δ = 7.90 (apparent d, 2 H), 7.80 (d, ³ J = 7.8 Hz, 1 H), 7.53 (d, ³ J = 7.3 Hz, 1 H), 7.36 (d, ³ J = 8.0 Hz, 1 H), 7.19-7.26 (m, 2 H), 7.05 (d, ³ J = 7.8 Hz, 1 H), 2.50 (s, 3 H).

¹³C NMR (CDCl3): δ = 146.24 (Cq), 143.06 (Cq), 141.54 (Cq), 135.23 (CH), 129.97 (CH), 127.17 (Cq), 126.58 (CH), 124.48 (CH), 123.44 (CH), 121.13 (CH), 109.90 (CH), 21.53 (CH3) (one CH overlapping and one Cq not apparent).

MS: m/z (%) = 253 (100) [M+], 211 (31), 195 (83), 183 (25), 91 (22), 77 (96).

HRMS: m/z [M+] calcd for C14H11N3O2: 253.08458; found: 253.08481.

5,6-Dimethyl-1-(4-methyl-2-nitrophenyl)-1 H -benzimidazole (28)

Application of Method 4 on a 3.3 mmol scale gave 28; yield: 0.49 g (53%); mp 182 ˚C.

¹H NMR (CDCl3): δ = 7.87 (d, 4 J = 1.1 Hz 1 H), 7.81 (s, 1 H), 7.51 (m, 2 H), 7.36 (d, ³ J = 8.1 Hz, 1 H), 6.81 (s, 1 H), 2.50 (s, 3 H), 2.31 (s, 3 H), 2.24 (s, 3 H).

¹³C NMR (CDCl3): δ = 145.37 (Cq), 141.65 (CH), 140.65 (Cq), 134.61 (CH), 133.16 (Cq), 132.91 (Cq), 131.88 (Cq), 129.30 (CH), 126.85 (Cq), 125.87 (CH), 120.45 (CH), 109.44 (CH), 20.90 (CH3), 20.32 (CH3), 20.93 (CH3) (one Cq not apparent).

MS: m/z (%) = 281 (100) [M+], 239 (33), 223 (56), 219 (21), 208 (18).

HRMS: m/z [M+] calcd for C16H15N3O2: 281.11588; found: 281.11571.

1-(3-Nitropyridin-2-yl)-1 H -benzimidazole (29)

Application of Method 4 on a 5.0 mmol scale gave 29; yield: 0.39 g (33%); mp 45 ˚C.

¹H NMR (CDCl3): δ = 8.79 (dd, ³ J = 4.7 Hz, 4 J = 1.7 Hz, 1 H), 8.44 (dd, ³ J = 8.1 Hz, 4 J = 1.6 Hz, 1 H), 8.21 (s, 1 H), 7.82 (m, 1 H), 7.54 (m, 1 H), 7.33-7.19 (m, 3 H).

¹³C NMR (CDCl3) (CH signals only): δ = 152.97, 141.61, 135.06, 124.51, 123.77, 123.26, 120.98, 110.34.

MS: m/z (%) = 240 (25) [M+], 195 (100), 194 (43), 169 (38), 118 (56).

HRMS: m/z [M+] calcd for C12H8N4O2: 240.06418; found: 240.06430.

FVP Reactions of N -(2-Nitrophenyl) Heterocycles [¹] [²]

The nitro compound was sublimed under vacuum through a silica furnace tube (35 × 2.5 cm). The solid product(s) were collected on a cold-finger trap cooled with a dry-ice/acetone mixture and positioned at the exit point of the furnace. A U-tube trap, cooled with liquid N2, was placed between the cold finger and the pump to trap the NOx byproducts. Upon completion of the pyrolysis, N2 gas was released through the system, which was then dismantled. The U-tube was allowed to warm to r.t. in a fume cupboard. Pyrolysis conditions are quoted as follows: substrate, quantity, furnace temperature (T f ), inlet temperature (T i ), pressure range (P), pyrolysis time (t), and product(s). Each pyrolysate was dissolved in CH2Cl2 and pre-adsorbed onto silica gel for purification by dry flash chromatography.

Note that for small-scale reactions (< 100 mg), a standard U-tube trap [¹²] at the exit point of the furnace gives satisfactory results.

Pyrido[2,3- b ]pyrrolo[3,2,1- hi ]indole (7-Azapyrrolo[3,2,1- jk ]carbazole) (18)

The pyrolysate obtained by FVP of 1-(3-nitropyridin-2-yl)-1H-indole [6, 0.500 g (2.09 mmol), T f = 875 ˚C, T i = 170 ˚C, P = 2.4 × 10-² Torr, t = 40 min] was purified by dry flash chromatography (hexane-EtOAc) to give 18; yield: 0.221 g (55%); mp 99-100 ˚C.

¹H NMR (CDCl3): δ = 8.42 (dd, ³ J = 5.1 Hz, 4 J = 1.6 Hz, 1 H), 8.29 (dd, ³ J = 7.7 Hz, 4 J = 1.6 Hz, 1 H), 7.93 (d, ³ J = 3.5 Hz, 1 H), 7.86 (d, ³ J = 7.4 Hz, 1 H), 7.83 (d, ³ J = 7.4 Hz, 1 H), 7.53 (t, ³ J = 7.4 Hz, 1 H), 7.24 (dd, ³ J = 7.7 Hz, ³ J = 5.1 Hz, 1 H), 6.91 (d, ³ J = 3.5 Hz, 1 H).

¹³C NMR (CDCl3): δ = 145.25 (Cq), 140.17 (CH), 130.66 (Cq), 124.55 (Cq), 123.83 (CH), 122.41 (Cq), 122.14 (CH), 122.01 (Cq), 121.95 (CH), 117.90 (CH), 117.69 (CH) 115.95 (CH), 110.84 (CH).

MS: m/z (%) = 192 (100) [M+], 164 (31), 138 (12), 96 (38), 82 (21), 69 (10).

Anal. Calcd for C13H8N2: C, 81.25; H, 4.2; N, 14.6. Found: C, 81.0; H, 4.25; N, 14.5.

Pyrido[4,3- b ]pyrrolo[3,2,1- hi ]indole (9-Azapyrrolo[3,2,1- jk ]carbazole) (19)

The pyrolysate obtained by FVP of 1-(3-nitropyridin-4-yl)-1H-indole [7, 0.506 g (2.12 mmol), T f = 875 ˚C, T i = 140 ˚C, P = 4.0 × 10-² Torr, t = 35 min] was purified by dry flash chromatography (hexane-EtOAc) to give 19; yield: 0.203 g (50%); mp 122-123 ˚C.

¹H NMR (CDCl3): δ = 9.25 (d, 4 J = 0.9 Hz, 1 H), 8.62 (d, ³ J = 5.7 Hz, 1 H), 7.91 (d, ³ J = 7.4 Hz, 1 H), 7.79 (d, ³ J = 7.4 Hz, 1 H), 7.67 (d, ³ J = 3.2 Hz, 1 H), 7.54 (t, ³ J = 7.4 Hz, 1 H), 7.52 (d, ³ J = 5.7 Hz, 1 H), 6.91 (d, ³ J = 3.2 Hz, 1 H).

¹³C NMR (CDCl3): δ = 146.73 (CH), 144.25 (CH), 143.33 (Cq), 140.78 (Cq), 126.77 (Cq), 124.36 (CH), 122.38 (CH), 121.90 (CH), 121.50 (Cq), 118.28 (CH), 116.27 (Cq), 111.89 (CH), 106.87 (CH).

MS: m/z (%) = 192 (100) [M+], 164 (72), 138 (55), 114 (22), 96 (54), 83 (70), 63 (44), 50 (24).

HRMS: m/z [M+] calcd for C13H8N2: 192.0688; found: 192.0690.

Pyrido[3′,2′:4,5]pyrrolo[3,2,1- jk ]carbazole (20)

FVP of 9-(3-nitropyridin-2-yl)-9H -carbazole [10, 0.500 g (1.73 mmol), T f = 875 ˚C, T i = 170 ˚C, P = 2.4 × 10-² Torr, t = 40 min] gave a pyrolysate that was purified by dry flash chromatography (hexane-EtOAc) to give 20; yield: 0.356 g (85%); mp 149-150 ˚C.

¹H NMR (CDCl3): δ = 8.53 (dd, ³ J = 5.1 Hz, 4 J = 1.4 Hz, 1 H), 8.33 (dd, ³ J = 7.8 Hz, 4 J = 1.4 Hz, 1 H), 8.28 (dd, ³ J = 7.7 Hz, 4 J = 1.0 Hz, 1 H), 8.10 (d, ³ J = 7.8 Hz, 1 H), 8.05 (d, ³ J = 7.5 Hz, 1 H), 7.98 (d, ³ J = 7.5 Hz, 1 H), 7.60 (m, 2 H), 7.39 (td, ³ J = 7.7 Hz, 4 J = 1.5 Hz, 1 H), 7.31 (dd, ³ J = 7.8 Hz, ³ J = 5.1 Hz, 1 H).

¹³C NMR (CDCl3): δ = 149.92 (Cq), 145.11 (CH), 142.57 (Cq), 137.81 (Cq), 130.86 (CH), 129.95 (Cq), 127.13 (CH), 123.70 (Cq), 123.30 (CH), 122.74 (CH), 122.66 (CH) 120.21 (CH), 119.68 (CH), 118.94 (Cq), 116.91 (Cq), 115.49 (CH), 113.92 (CH).

MS: m/z (%) = 242 (100) [M+], 214 (20), 188 (7), 167 (15), 139 (3), 121 (52), 93 (17), 81 (6).

HRMS: m/z [M+] calcd for C17H10N2: 242.0843; found: 242.0842.

Pyrido[3′,4′:4,5]pyrrolo[3,2,1-jk]carbazole (21)

The pyrolysate obtained by FVP of 9-(3-nitropyridin-4-yl)-9H-carbazole [11, 0.492 g (1.70 mmol), T f = 875 ˚C, T i = 150-190 ˚C, P = 3.0 × 10-² Torr, t = 60 min] was purified by dry flash chromatography (hexane-EtOAc) to give 21; yield: 0.227 g (55%); mp 155-156 ˚C.

¹H NMR (CDCl3): δ = 9.25 (s, 1 H), 8.63 (d, ³ J = 5.6 Hz, 1 H), 8.02 (d, ³ J = 7.8 Hz, 1 H), 7.95 (d, ³ J = 7.5 Hz, 1 H), 7.93 (d, ³ J = 7.5 Hz, 1 H), 7.73 (d, ³ J = 7.8 Hz, 1 H), 7.63 (d, ³ J = 5.6 Hz, 1 H), 7.54 (t, ³ J = 7.5 Hz, 1 H), 7.50 (td, ³ J = 7.8 Hz, 4 J = 1.0 Hz, 1 H), 7.35 (td, ³ J = 7.5 Hz, 4 J = 1.0 Hz, 1 H).

¹³C NMR (CDCl3): δ = 146.37 (CH), 144.39 (CH), 143.26 (Cq), 142.09 (Cq), 137.88 (Cq), 130.40 (Cq), 126.89 (CH), 125.81 (Cq), 123.87 (CH), 123.11 (CH), 122.78 (CH), 120.01 (CH), 119.76 (CH), 118.52 (Cq), 115.89 (Cq), 112.55 (CH), 107.22 (CH).

MS: m/z (%) = 242 (100) [M+], 214 (14), 187 (5), 121 (17), 107 (17) 93 (11).

HRMS: m/z [M+] calcd for C17H10N2: 242.0843; found: 242.0847.

Pyrido[2,3- b ]pyrido[3′,2′:4,5]pyrrolo[3,2,1- hi ]indole (22)

The pyrolysate obtained by FVP of 9-(3-nitropyridin-2-yl)-9H-pyrido[2,3-b]indole [12, 0.073 g (0.25 mmol), T f = 875 ˚C, T i = 80-120 ˚C, P = 4.0 × 10-² Torr, t = 20 min] was purified by dry flash chromatography (hexane-EtOAc) to give 22; yield: 0.37 g (60%); mp 152-153 ˚C.

¹H NMR (CDCl3): δ = 8.62 (dd, ³ J = 5.0 Hz, 4 J = 1.6 Hz, 2 H), 8.35 (dd, ³ J = 7.6 Hz, 4 J = 1.6 Hz, 2 H), 8.02 (d, ³ J = 7.5 Hz, 2 H), 7.61 (t, ³ J = 7.5 Hz, 1 H), 7.80 (dd, ³ J = 7.6 Hz, ³ J = 5.0 Hz, 2 H).

¹³C NMR (CDCl3): δ = 150.16 (2 Cq), 146.63 (2 CH), 141.67 (Cq), 130.75 (2 CH), 123.69 (2 Cq), 123.67 (CH), 120.72 (2 CH), 117.93 (2 CH), 116.34 (2 Cq).

MS: m/z (%) = 243 (30) [M+], 190 (72), 156 (100), 128 (26), 78 (15).

HRMS: m/z [M+] calcd for C16H9N3: 243.0797; found: 243.0797.

9 H -Carbazole-1-carbonitrile (25)

Method 1: The pyrolysate obtained by FVP of 1-(2-nitrophenyl)-1H-benzimidazole [16, 0.500 g (2.09 mmol), T f = 850 ˚C, T i = 160-180 ˚C, P = 0.0034 Torr, t = 20 min] was subjected to dry flash chromatography (silica gel, hexane-EtOAc) to give 25; yield: 0.26 g (64%); mp 189-190 ˚C (Lit. [¹³] 188-189 ˚C) (NMR data as below).

Method 2: The pyrolysate obtained by FVP of 1-(2-nitrophenyl)-1H-indazole [17, 0.350 g (1.46 mmol), T f = 850 ˚C, T i = 250-270 ˚C, P = 0.013 Torr, t = 30 min] was subjected to dry flash chromatography (silica gel, hexane-EtOAc) to give 25; yield: 0.16 g (57%); mp 189-190 ˚C (Lit. [¹³] 188-189 ˚C).

¹H NMR (CDCl3): δ = 9.00 (br s, 1 H), 8.27 (dt, ³ J = 7.7 Hz, 4 J = 1.1 Hz, 1 H), 8.08 (ddd, ³ J = 6.9 Hz, 4 J = 1.7 Hz, 5 J = 0.9 Hz, 1 H), 7.68 (dd, ³ J = 7.7 Hz, 4 J = 1.1 Hz, 1 H), 7.45-7.57 (m, 2 H), 7.29 (dd, ³ J = 6.5 Hz, 4 J = 1.4 Hz, 1 H), 7.25 (t, ³ J = 7.7 Hz, 1 H).

¹³C NMR (CDCl3): δ = 140.49 (Cq), 139.38 (Cq), 129.06 (CH), 127.18 (CH), 125.07 (CH), 124.23 (Cq), 122.42 (Cq), 120.55 (2 CH), 119.18 (CH), 117.25 (Cq), 111.20 (CH), 93.50 (Cq).

MS: m/z (%) = 192 (100) [M+], 164 (15), 138 (5), 96 (7).

3,4-Dimethyl-9 H -carbazole-1-carbonitrile (30)

The pyrolysate obtained by FVP of 5,6-dimethyl-1-(2-nitrophenyl)-1H-benzimidazole [26, (0.442 g (1.66 mmol), T f = 850 ˚C, T i = 160-180 ˚C, P = 0.04 Torr, t = 40 min] was subjected to dry flash chromatography (silica gel, hexane-EtOAc) to give 30; yield: 0.215 g (59%); mp 215 ˚C.

¹H NMR (CDCl3): δ = 8.51 (br s, 1 H), 8.15 (d, ³ J = 8.1 Hz, 1 H), 7.38-7.43 (m, 3 H), 7.30 (m, 1 H), 2.77 (m, 3 H), 2.40 (m, 3 H).

MS: m/z (%) = 220 (100) [M+], 205 (97), 194 (51), 180 (42), 73 (37).

HRMS: m/z [M+] calcd for C15H12N2: 220.09950; found: 220.09845.

6-Methyl-9 H -carbazole-1-carbonitrile (31)

The pyrolysate obtained by FVP of 1-(4-methyl-2-nitrophenyl)-1H-benzimidazole [27, 26 mg (0.10 mmol), T f = 850 ˚C, T i = 150 ˚C, P = 0.065 Torr, t = 15 min) gave 31; yield: 13 mg (60%); mp 185 ˚C.

¹H NMR (CDCl3): δ = 8.58 (s, 1 H), 8.16 (d, ³ J = 7.5 Hz, 1 H), 8.05 (s, 1 H), 7.59 (dd, ³ J = 7.6 Hz, 4 J = 1.0 Hz, 1 H), 7.40-7.15 (m, 3 H), 2.47 (s, 3 H).

¹³C NMR (CDCl3): δ (non-Cq signals only) = 129.03, 125.22, 128.68, 120.53, 119.12, 110.72, 18.55 (CH3).

MS: m/z (%) = 206 (100) [M+], 205 (83), 177 (8), 151 (8), 103 (10).

HRMS: m/z [M+] calcd for C14H10N2: 206.08385; found: 206.08340.

3,4,6-Trimethyl-9 H -carbazole-1-carbonitrile (32)

The pyrolysate obtained by FVP of 5,6-dimethyl-l-(4-methyl-2-nitrophenyl)-1H-benzimidazole [28, 55 mg (0.20 mmol), T f = 850 ˚C, T i = 170-185 ˚C, P = 0.018 Torr, t = 15 min] gave 32; yield: 27 mg (58%); mp 228 ˚C.

¹H NMR (CDCl3): δ = 8.42 (br s, 1 H), 7.92 (s, 1 H), 7.40-7.27 (m, 3 H), 2.78 (s, 3 H), 2.51 (s, 3 H), 2.38 (s, 3 H).

MS: m/z (%) = 234 (100) [M+], 233 (40), 220 (16), 219 (45), 109 (8).

HRMS: m/z [M+] calcd for C16H14N2: 234.11515; found: 234.11490.

9 H -Pyrido[2,3- b ]indole-8-carbonitrile (33)

The pyrolysate obtained by FVP of (3-nitropyridin-2-yl)-1H-benzimidazole [29, 303 mg (1.26 mmol), T f = 850 ˚C, T i = 180-200 ˚C, P = 0.075 Torr, t = 40 min] gave 33; yield: 136 mg (56%).

¹H NMR (DMSO-d 6): δ = 12.76 (br s, 1 H), 8.79 (dd, ³ J = 4.7 Hz, 4 J = 1.7 Hz, 1 H), 8.50-8.55 (m, 2 H), 7.90 (dd, ³ J = 4.5 Hz, 4 J = 1.7 Hz, 1 H), 7.40-7.27 (m, 2 H).

¹³C NMR (DMSO-d 6): δ (CH signals only, from HSQC spectrum) = 147.64 (CH), 131.06 (CH), 129.45 (CH), 126.60 (CH), 119.60 (CH), 116.34 (CH).

MS: m/z (%) = 193 (100) [M+], 166 (46), 164 (33), 139 (46), 138 (21), 88 (17).

HRMS: m/z [M+] calcd for C12H7N3: 193.06345; found: 193.06431.

Acknowledgment

We are grateful to The Engineering and Physical Sciences Research Council (UK) for research studentships for L.A.C. and S.I.W.

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