Oxidative heterocyclization of 2-alkynylbenzaldehydes with 1,2- phenylenediamine

Article abstract of DOI:10.1002/(SICI)1099-0690(200004)2000:8<1433::AID-EJOC1433>3.0.CO;2-7

Upon condensation of ortho-phenylenediamine (2) with ortho- alkynylbenzaldehydes in nitrobenzene, oxidative cyclizations are observed, which result in benzimidazo[2,1-a]isoquinolines (8) or isoindolo[2,1- a]quinoxalines (9) depending on the influence of additional substituents at the alkyne.

Full text of DOI:10.1002/(SICI)1099-0690(200004)2000:8<1433::AID-EJOC1433>3.0.CO;2-7

FULL PAPER
Oxidative Heterocyclization of 2-Alkynylbenzaldehydes with 1,2-
Phenylenediamine
Gerald Dyker,*[a] Wolfgang Stirner,[a] and Gerald Henkel[a]
Keywords: Alkynes / Annelation reactions / Carbonyl compounds / Hetarenes / Polycycles
Upon condensation of ortho-phenylenediamine (2) with or-
tho-alkynylbenzaldehydes in nitrobenzene, oxidative cycli-
zations are observed, which result in benzimidazo[2,1-a]iso-
quinolines (8) or isoindolo[2,1-a]quinoxalines (9) depending
on the influence of additional substituents at the alkyne.
Introduction
Aryl-substituted carbonyl compounds with an alkynyl
group in the ortho-position, and their imino derivatives, are
prone to undergo cyclization reactions, especially when aro-
matic intermediates or products are formed thereby.[1] Re-
cently, we described a rearrangement reaction based on
such an initial cyclization of
a
bis(alkynyl)benzil.[2]
In the case of the condensation reaction of the bis(al-
dehyde) 1 with one equivalent of ortho-phenylene diamine
(2) we originally intended to test the feasibility of the
formation of a macrocyclic bis(imine) and were surprised
to find the benzimidazo[2,1-a]isoquinoline (3) as the main
product (Scheme 1): obviously a disproportionation had
taken place, with the oxidation of one aldehyde carbon
atom, presumably after the condensation with 2, and the
reduction of the other one to give a hydroxymethyl group.[3]
This result suggests that an external oxidizing agent should
enhance the formation of the benzimidazoisoquinoline moi-
ety and, indeed, with two equivalents of 2 and with nitro-
benzene[4] as the solvent we could isolate 4 as the product
of a twofold oxidative heterocyclization. In this article we
report on the scope and limitations and present a mechan-
istic interpretation of this type of heterocyclization.
The formation of the benzimidazo[2,1-a]isoquinoline
moiety is not without precedent: Sun and LaVoie[1b] de-
scribed a related annulation reaction of a functionalized
benzimidazole, but catalyzed by palladium acetate. In order
to test the scope and limitations of our oxidative heterocy-
clization we synthesized the 2-alkynylbenzaldehydes 7 as
model compounds by a Sonogashira coupling reaction.[5]
Starting from the 2-bromobenzaldehydes 5 and various ter-
minal alkynes 6 moderate to good yields were obtained
(Scheme 2), accept for 2-ethynylpyridine (6c). In this case
the yield dropped below 20%, but nevertheless gave suffi-
cient material for our purposes.
Scheme 1. Condensation of phenylenediamine 2 with bis(aldehyde)
1 under neutral and under oxidative conditions
[a]
Fachbereich 6, Institut für Synthesechemie der
Gerhard-Mercator-Universität-GH Duisburg
Lotharstraße 1, D-47048 Duisburg, Germany
Fax: (internat.) ϩ 49-203/379-4192
Scheme 2. Reaction conditions: a. 1 mol-% Pd(OAc)2, 2 mol-%
PPh3, 1.4–2 mol-% CuI (none in case of 7.2b), Et3N, Ar, 80 °C, 10 h
E-mail: dyker@uni-duisburg.de
Eur. J. Org. Chem. 2000, 1433Ϫ1441
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0408Ϫ1433 $ 17.50ϩ.50/0
1433

G. Dyker, W. Stirner, G. Henkel
FULL PAPER
The oxidative cyclization of the functionalized aldehydes that, in contrast to 10.1b, the aryl substituent prefers an
7 with ortho-phenylene diamine (2) in nitrobenzene led, as almost coplanar confirmation in the solid state (Figure 1,
expected, to the formation of the benzimidazo[2,1-a]isoqui- b). The same seems to be true for the preferred conforma-
1
1
nolines 8 in up to 88% yield (Scheme 3, Table 1). In the H tion in solution: in the H NMR spectrum of 11.1e the sig-
NMR spectra of 8 and of the corresponding HBF4 salts 10 nal of H-7 is observed at 8.33 ppm which is in agreement
the signal of the ‘‘bay region’’ proton 1-H is shifted to rela- with an anisotropic down-field shift of the neighbouring
tively low field at 8.9 ppm; only in the case of 8.2b, with aryl-group.
the additional hydroxyl-substituent in the 2-position, is the
Our mechanistic considerations for the formation of the
signal of 1-H seen at 8.06 ppm. For those benzimidazoiso- benzimidazoisoquinolines 8 are exemplified with the phenyl
quinolines 8 and 10 with an aryl-substituent in the 6-position derivative 8.1b (Scheme 4). We assume that the benzimid-
the signal of 8-H is found at remarkably high field between azole 15.1b is formed as a key intermediate either directly
6.39 and 6.66 ppm. This can be explained by an anisotropic during oxidation of the Schiff base 12.1b or by oxidation of
up-field shift of about 1.5 ppm relative to the butyl-substi- the N,N-acetal 13.1b. The oxidation with nitrobenzene
tuted derivative 8.1a and indicates a perpendicular con- should take place via radical cations as described in the
formation of the aryl-substituent. This special geometry was
confirmed by the X-ray structure of 10.1b (Figure 1, a).[6]
Scheme 3. Oxidative cyclization of functionalized benzaldehydes 7
with ortho-phenylene diamine (2) and corresponding HBF4 salts of
the cyclization products
Scheme 4. Proposed mechanistic pathway to benzimidazo[2,1-a]iso-
quinoline 8.1b
Table 1. Yields and product ratio of benzimidazo[2,1-a]isoquinol-
ines 8 and isoindolo[2,1-a]quinoxalines 9 (product ratio based on
1H NMR spectrum of the crude product)
Entry
R
R1
Products Yield [%] Ratio
1
2
3
4
5
6
7
H
H
H
H
H
H
n-butyl
8.1a/9.1a 46
8.1b/9.1b 83
8.1c/9.1c 38
8.1d/9.1d 44
8.1e/9.1e 55
100:0
100:0
100:0
7:93
9:91
100:0
100:0
phenyl
2-pyridyl
2-furyl
2-(5-methylfuryl)
2,4-dimethoxyphenyl 8.1f/9.1f 64
OH phenyl
8.2b/9.2b 88
Exclusively in cases where 7 had a furyl substituent con-
nected to the alkyne, the isoindolo[2,1-a]quinoxalines 9 be-
came the main products of the heterocyclization (Table 1,
entries 4 and 5). Since these hetarenes are rather sensitive
they were characterized as their HBF4 salts 11. From 11.1e
with a methylfuryl substituent we obtained single crystals
Scheme 5. Products of the oxidative cyclization of functionalized
suitable for an X-ray structure analysis,[6] which revealed stilbene 16 with ortho-phenylenediamine (2)
1434
Eur. J. Org. Chem. 2000, 1433Ϫ1441

Oxidative Heterocyclization of 2-Alkynylbenzaldehydes with 1,2-Phenylenediamine
FULL PAPER
Figure 1. Perspective views of the X-ray structures of a) 10.1b and b) 11.1e
literature.[4] Presumably the final cyclization is initialized by ent no quinoxaline is observed (Table 1, entry 6). Therefore
protonation of the alkyne to give the vinylic cation 14.1b. we assume that, in the case of the furyl-substituted starting
This mechanistic scheme is further supported by the result materials 7.1d and 7.1e, the cyclization at the alkyne is initi-
of the related oxidative condensation of the stilbene derivat- ated by protonation of the furan ring rather than by pro-
ive 16 with 2 (Scheme 5). In this case we could isolate both tonation of the alkyne itself (Scheme 6). The first cycliza-
the imidazole 17 and its annulation product 18; the latter is tion of the cationic intermediate 19.1d leads to the forma-
slowly oxidized under the reaction conditions to give the tion of the isoindole moiety; 21.1d is then activated for a
final product 8.1b.
second cyclization to give 20.1d. The subsequent depro-
In order to explain the formation of isoindoloquinoxal- tonation and oxidation is a reasonable pathway to the ob-
ines 9 it is important to ascertain that the unique behaviour served product 9.1d.
of the furyl-substituted starting materials 7.1d and 7.1e is
In summary, we have developed a domino process to
not due to their influence as electron-rich ϩM-substituents benzimidazo[2,1-a]isoquinolines (8) and, in special cases, to
with the similar electron-rich 2,4-dimethoxyphenyl substitu- isoindolo[2,1-a]quinoxalines (9), thus proving once more
Eur. J. Org. Chem. 2000, 1433Ϫ1441
1435

G. Dyker, W. Stirner, G. Henkel
FULL PAPER
1424 (w), 1392 (w), 1340 (w), 1275 (w), 1247 (w), 1190 (m), 825
(w), 766 (m), 638 (w). – UV/Vis (acetonitrile): λmax (lg ε) ϭ 232 nm
(4.84), 258 (4.32), 265 (4.25, sh), 317 (3.79). – 1H NMR (500 MHz):
δ ϭ 1.85 ("quint", "J" ϭ 3.0 Hz, 4 H), 2.58 ("quint", "J" ϭ 2.8 Hz,
4 H), 7.37–7.41 (m, 2 H), 7.51–7.53 (m, 4 H), 7.88 ("dt", "J" ϭ 7.5,
0.8 Hz, 2 H), 10.54 ("t", "J" ϭ 0.7 Hz, 2 H). – 13C NMR
(126 MHz): δ ϭ 19.3 (t), 27.7 (t), 76.9 (s), 97.2 (s), 127.1 (d), 127.7
(s), 128.1 (d), 133.4 (d), 133.8 (d), 136.0 (s), 192.1 (d). – MS (70 eV);
m/z (%): 314 (6) [Mϩ], 313 (10) [Mϩ – 1], 296 (12), 285 (51), 283
(23), 269 (22), 268 (33), 267 (27), 258 (27), 257 (52), 229 (30), 228
(22), 215 (37), 144 (21), 129 (24), 128 (43), 116 (21), 115 (100), 89
(27). – C22H18O2 (314.4): calcd. C 84.05, H 5.77; found C 84.09,
H 5.74.
2-(1-Hexyn-1-yl)benzaldehyde (7.1a): From 1-hexyne (6a) (1.52 g,
20 mmol) and 2-bromobenzaldehyde (5.1; 4.0 g, 2.5 mL,
21.5 mmol). TLC of the crude product (silica, petroleum ether/
methyl tert-butyl ether 9:1): Rf ϭ 0.63, 0.50, 0.42. The fraction with
Rf ϭ 0.50 was isolated by flash chromatography and dried in vacuo
(10 mbar, 50 °C) to give 7.1a (1.75 g, 47%) as a brownish oil. The
1
NMR spectra were in agreement with reported data.[7] – H NMR
(500 MHz): δ ϭ 0.97 (t, J ϭ 7.4 Hz, 3 H), 1.50 ("q", "J" ϭ 7.5 Hz,
2 H), 1.63 (m, 2 H), 2.49 (t, J ϭ 7.1 Hz, 2 H), 7.36–7.40 (m, 1 H),
7.49–7.54 (m, 2 H), 7.89 (ddd, J ϭ 7.8, 1.4, 0.8 Hz, 1 H), 10.54 (d,
J ϭ 0.8 Hz, 1 H). – 13C NMR (126 MHz): δ ϭ 13.6 (q), 19.3 (t),
22.1 (t), 30.6 (t), 76.3 (s), 98.2 (s), 126.9 (d), 127.9 (d), 128.0 (s),
133.3 (d), 133.7 (d), 136.0 (s), 192.3 (d).
Scheme 6. Proposed mechanistic pathway to isoindolo[2,1-a]quin-
oxaline 9.1d
2-(Phenylethynyl)benzaldehyde (7.1b): From ethynylbenzene (6b;
2.04 g, 20 mmol) and 2-bromobenzaldehyde (5.1; 4.0 g, 2.5 mL,
21.5 mmol). TLC of the crude product (silica, petroleum ether/
methyl tert-butyl ether 3:1): Rf ϭ 0.69, 0.56, 0.38. The fraction with
Rf ϭ 0.56 was isolated by flash chromatography and dried in vacuo
(10 mbar, 50 °C) to give 7.1b (3.61 g, 88%) as a brownish oil. The
the feasibility of annelation reactions of ortho-func-
tionalized arylalkynes.
Experimental Section
1
NMR spectra were in agreement with reported data.[7] – H NMR
General: m.p. (uncorrected): Reichert Thermovar. – IR: Perkin–
Elmer 983. – UV: Perkin–Elmer 554. – NMR: Bruker DRX 500,
Bruker WM 300; 1H NMR spectra (500 MHz or 300 MHz) were re-
corded in CDCl3 (unless otherwise stated) with TMS as the internal
standard; 13C NMR spectra (125.8 MHz or 75.5 MHz) were re-
corded in CDCl3 which was also used as the internal standard (unless
otherwise stated). – MS: MAT 311A (70 eV). – For analytical TLC
precoated plastic sheets ‘‘POLYGRAM SIL G/UV254’’ from Mach-
erey–Nagel were used. 2-Ethynylpyridine (6c) was bought from
Lancaster and used without further purification.
(500 MHz): δ ϭ 7.37–7.40 (m, 3 H), 7.44 ("dd", "J" ϭ 8.1, 7.6 Hz,
1 H), 7.55–7.57 (m, 2 H), 7.58 (dd, J ϭ 6.1, 1.4 Hz, 1 H), 7.64
(ddd, J ϭ 7.7, 1.3, 0.5 Hz, 1 H), 7.95 (ddd, J ϭ 7.8, 1.4, 0.5 Hz, 1
H), 10.66 (d, J ϭ 0.8 Hz, 1 H).
2-(2-Pyridylethynyl)benzaldehyde (7.1c): From 2-ethynylpyridine
(6c; 0.50 g, 4.9 mmol) and 2-bromobenzaldehyde (5.1; 0.90 g,
0.56 mL, 4.9 mmol). A quarter of the amount of reagents from
the general procedure was used. TLC of the crude product (silica,
petroleum ether/methyl tert-butyl ether 3:1): Rf ϭ 0.73, 0.28, 0.09.
The fraction with Rf ϭ 0.28 was isolated by flash chromatography
and dried in vacuo (10 mbar, 50 °C) to give 7.1c (0.19 g, 19%) as
a slightly yellow solid with m.p. 43–44 °C. – IR (KBr): ν˜ ϭ 3062
cm–1 (w), 3004 (w), 2839 (w), 2749 (w), 2221 (w), 1696 (vs), 1592
(s), 1580 (s), 1559 (m), 1478 (s), 1461 (s), 1427 (m), 1281 (w), 1267
(m), 1194 (m), 1152 (w), 989 (w), 819 (m), 778 (s), 765 (s), 739 (w),
639 (m), 630 (w). – UV/Vis (acetonitrile): λmax (lg ε) ϭ 206 nm
(4.41), 226 (4.37), 246 (4.47), 270 (4.21), 278 (4.21), 286 (4.30), 294
2-Alkynylbenzaldehydes 1 and 7. – General Procedure: A mixture of
the terminal alkyne (20 mmol), a small excess of 2-bromobenzal-
dehyde (5), CuI (76 mg, 0.40 mmol), palladium acetate (45 mg,
0.20 mmol) and triphenylphosphane (105 mg, 0.400 mmol) in tri-
ethylamine (40 mL) was heated at 80 °C for 10 h under argon in a
screw-capped tube (deviations from the usual amounts of reagents
are mentioned below for special cases). After filtration through sil-
ica with methyl tert-butyl ether the solvent was distilled off and the
residue fractionated by flash chromatography.
1
(4.34), 318 (4.08). – H NMR (500 MHz): δ ϭ 7.30 (ddd, J ϭ 7.6,
4.8, 1.2 Hz, 1 H), 7.49 ("td", "J" ϭ 7.5, 0.9 Hz, 1 H), 7.57–7.59 (m,
1 H), 7.60 ("td", "J" ϭ 7.5, 1.5 Hz, 1 H), 7.70–7.74 (m, 2 H), 7.96
(ddd, J ϭ 7.8, 1.5, 0.6 Hz, 1 H), 8.65 (ddd, J ϭ 4.8, 1.8, 1.0 Hz, 1
H), 10.66 (d, J ϭ 0.8 Hz, 1 H). – 13C NMR (126 MHz): δ ϭ 84.4
(s), 95.0 (s), 123.4 (d), 125.6 (s), 127.4 (d), 127.5 (d), 129.4 (d),
133.7 (d), 133.8 (d), 136.2 (s), 136.3 (d), 142.6 (s), 150.3 (d), 191.3
Bis(aldehyde) 1: From 1,7-octadiyne (2.1 g, 20 mmol) and 2-bromo-
benzaldehyde (5.1; 8.0 g, 5.0 mL, 43 mmol) and double the amount
of all reagents and solvents in the general procedure, since the al-
kyne is bifunctional in this case. TLC of the crude product (silica,
petroleum ether/methyl tert-butyl ether 2:1): Rf ϭ 0.60, 0.39, 0.00.
The fraction with Rf ϭ 0.39 was isolated by flash chromatography,
crystallized from petroleum ether/methyl tert-butyl ether (1:1) and
dried in vacuo (0.1 mbar, 50 °C) to give 1 (2.07 g, 33%) as colour-
less crystals, m.p. 76–77 °C. – IR (KBr): ν˜ ϭ 2941 cm–1 (w), 2839
(d). – MS (70 eV); m/z (%): 207 (21) [Mϩ], 180 (15), 179 (100) [Mϩ
–
CO], 178 (44), 152 (13), 151 (13), 76 (11). – C14H9NO (207.2):
calcd. C 81.14, H 4.38, N 6.76; found C 80.96, H 4.36, N 6.70.
2-(2-Furylethynyl)benzaldehyde (7.1d): From 2-ethynylfuran[8] (6d;
(w), 2753 (w), 1693 (s), 1594 (m), 1473 (m), 1461 (w), 1447 (w), 0.92 g, 10 mmol) and 2-bromobenzaldehyde (5.1; 1.9 g, 1.2 mL,
1436 Eur. J. Org. Chem. 2000, 1433Ϫ1441

Oxidative Heterocyclization of 2-Alkynylbenzaldehydes with 1,2-Phenylenediamine
FULL PAPER
10 mmol). Half of the amount of reagents from the general proced- "J" ϭ 7.5, 1.5 Hz, 1 H), 7.62 (ddd, J ϭ 7.8, 1.2, 0.5 Hz, 1 H), 7.93
ure was used. TLC of the crude product (silica, petroleum ether/
(ddd, J ϭ 7.8, 1.4, 0.5 Hz, 1 H), 10.73 (d, J ϭ 0.8 Hz, 1 H). – 13C
methyl tert-butyl ether 3:1): Rf ϭ 0.56, 0.33, 0.20. The fraction with NMR (126 MHz): δ ϭ 55.5 (q), 55.9 (q), 87.9 (s), 93.4 (s), 98.4 (d),
Rf ϭ 0.33 was isolated by flash chromatography and dried in vacuo
(10 mbar, 50 °C) to give 7.1d (1.05 g, 54%) as brownish needles
104.2 (s), 105.0 (d), 126.9 (d), 127.9 (s), 128.0 (d), 132.7 (d), 133.7
(d), 134.2 (d), 135.7 (s), 161.8 (s), 161.9 (s), 192.7 (d). – MS (70 eV);
with m.p. 30–31 °C. – IR (KBr): ν˜ ϭ 3151 cm–1 (w), 3065 (w), 2844 m/z (%): 267 (19) [Mϩ ϩ 1], 266 (100) [Mϩ], 251 (14), 249 (9), 238
(w), 2746 (w), 2206 (w), 1696 (s), 1594 (m), 1489 (w), 1467 (m), (9), 237 (25) [Mϩ – CHO], 223 (19), 221 (12), 180 (9), 165 (22), 152
1286 (w), 1265 (m), 1194 (m), 1170 (w), 1014 (m), 931 (m), 833 (w), (22). – C17H14O3 (266.3): calcd. C 76.68, H 5.30; found C 76.52,
799 (w), 761 (s), 643 (m), 609 (m). – UV/Vis (acetonitrile): λmax (lg H 5.30.
ε) ϭ 212 nm (4.20), 226 (4.17), 253 (4.40, sh), 257 (4.41), 292 (4.14),
300 (4.25), 335 (4.01). – H NMR (500 MHz): δ ϭ 6.47 (dd, J ϭ
5-Hydroxy-2-(phenylethynyl)benzaldehyde (7.2b): From ethynylben-
zene (6b; 2.0 g, 10 mmol) and 5-hydroxy-2-bromobenzaldehyde
1
3.5, 1.9 Hz, 1 H, 4Ј-H), 6.76 (dd, J ϭ 3.5, 0.7 Hz, 1 H, 3Ј-H), 7.45–
(5.2; 0.71 g, 3.8 mmol). Half the amount of reagents from the gen-
7.49 (m, 1 H), 7.48 (dd, J ϭ 1.9, 0.7 Hz, 1 H, 5Ј-H), 7.59 ("td",
eral procedure was used. TLC of the crude product (silica, petro-
"J" ϭ 7.5, 1.4 Hz, 1 H), 7.64 (ddd, J ϭ 7.7, 1.3, 0.6 Hz, 1 H), 7.95
leum ether/methyl tert-butyl ether 3:1): Rf ϭ 0.92, 0.86, 0.25, 0.22,
0.14. The fraction with Rf ϭ 0.22 was isolated by flash chromato-
graphy and dried in vacuo (10 mbar, 50 °C) to give 7.1f (575 mg,
26%) as a colourless solid, according to the NMR spectra pure
enough for further transformations. – 1H NMR (500 MHz): δ ϭ
7.12 (dd, J ϭ 8.4, 2.8 Hz, 1 H, 4-H), 7.37–7.38 (m, 3 H), 7.44 (dd,
J ϭ 2.7, 0.3 Hz, 1 H, 6-H), 7.53–7.55 (m, 2 H), 7.55 (dd, J ϭ 8.4,
0.4 Hz, 1 H, 3 H), 10.58 (s, 1 H). – 13C NMR (126 MHz): δ ϭ 84.8
(s), 94.8 (s), 113.1 (d), 119.6 (s), 122.0 (d), 122.7 (s), 128.5 (d, 2C),
128.8 (d), 131.6 (d, 2C), 135.0 (d), 137.2 (s), 156.4 (s), 192.1 (d).
(ddd, J ϭ 7.9, 1.3, 0.6 Hz, 1 H), 10.57 (d, J ϭ 0.8 Hz, 1 H). – 13C
NMR (126 MHz): δ ϭ 86.2 (s), 89.2 (s), 111.3 (d), 116.6 (d), 125.8
(s), 127.5 (d), 129.0 (d), 133.0 (d), 133.8 (d), 135.7 (s), 136.4 (s),
144.5 (d), 191.3 (d). – MS (70 eV); m/z (%): 197 (14) [Mϩ ϩ 1], 196
(100) [Mϩ], 168 (22) [Mϩ – CO], 140 (31), 139 (80), 114 (10), 113
(9), 63 (10). – C13H8O2 (196.2): calcd. C 79.57, H 4.11; found C
79.58, H 4.15.
2-[(5-Methyl-2-furyl)-ethynyl]benzaldehyde (7.1e): From 2-ethynyl-
5-methylfuran[9] (6e; 0.96 g, 9.0 mmol) and 2-bromobenzaldehyde
(5.1; 1.7 g, 1.1 mL, 9.2 mmol). Half of the amount of reagents from
the general procedure was used. TLC of the crude product (silica,
petroleum ether/methyl tert-butyl ether 15:1): Rf ϭ 0.50, 0.40, 0.33,
0.20. The fraction with Rf ϭ 0.33 was isolated by flash chromato-
graphy and dried in vacuo (10 mbar, 50 °C) to give 7.1e (1.15 g,
61%) as a brownish solid. Recrystallization from petroleum ether/
methyl tert-butyl ether 15:1 gave colourless crystals with m.p. 70–
71 °C. – IR (KBr): ν˜ ϭ 3125 cm–1 (w), 2926 (w), 2842 (w), 2754
(w), 2198 (m), 1692 (s), 1596 (m), 1564 (w), 1533 (m), 1469 (m),
1448 (w), 1394 (w), 1311 (w), 1292 (w), 1266 (m), 1196 (s), 1023
(m), 834 (w), 797 (m), 763 (s), 642 (w). – UV/Vis (acetonitrile): λmax
(lg ε) ϭ 215 nm (4.23), 227 (4.21, sh), 260 (4.34), 298 (4.08, sh),
306 (4.16), 344 (3.98). – 1H NMR (500 MHz): δ ϭ 2.35 (t, J ϭ
0.5 Hz, 3 H), 6.05 ("dq", "J" ϭ 3.3, 1.0 Hz, 1 H), 6.65 (dd, J ϭ 3.3,
0.4 Hz, 1 H), 7.43 ("td", "J" ϭ 7.9, 1.3, 0.9 Hz, 1 H), 7.56 ("td",
"J" ϭ 7.5, 1.4 Hz, 1 H), 7.60 ("dt", "J" ϭ 7.8, 0.8 Hz, 1 H), 7.93
("dt", "J" ϭ 7.9, 0.7 Hz, 1 H), 10.56 (d, J ϭ 0.8 Hz, 1 H). – 13C
NMR (126 MHz): δ ϭ 13.9 (q), 86.8 (s), 89.0 (s), 107.6 (d), 118.0
(d), 126.2 (s), 127.3 (d), 128.7 (d), 132.7 (d), 133.8 (d), 134.5 (s),
135.5 (s), 154.8 (s), 191.4 (d). – MS (70 eV); m/z (%): 211 (23) [Mϩ
ϩ 1], 210 (100) [Mϩ], 209 (19) [Mϩ – 1], 181 (26), 168 (14), 167
(24), 153 (24), 152 (16), 139 (27), 43 (26). – C21H14N2 (210.2): calcd.
C 79.98, H 4.79; found C 79.83, H 4.76.
Redox Reaction of Bis(benzaldehyde) 1 With ortho-Phenylenedi-
amine (2): A solution of bis(benzaldehyde) 1 (500 mg, 1.59 mmol)
and diamine 2 (172 mg, 1.59 mmol) in 50 mL of toluene was re-
fluxed at the Dean-Stark trap for 7 d. The crude product was
recrystallized from dichloromethane/n-pentane to give 330 mg
(54%) of 3 as a colourless solid with m.p. 193–197 °C. – IR (KBr):
ν˜ ϭ 3197 cm–1 (m, br), 3057 (m), 2942 (m), 2861 (m), 1642 (w),
1527 (s), 1477 (w), 1452 (s), 1370 (w), 1337 (m), 1294 (w), 1283 (w),
1235 (w), 1052 (m), 1020 (w), 834 (w), 767 (s), 754 (s), 735 (s). –
UV/Vis (dichloromethane): λmax (lg ε) ϭ 240 nm (4.45), 256 (4.37),
269 (4.44), 279 (4.53), 313 (3.81), 339 (3.71), 357 (3.66). – 1H NMR
(500 MHz): δ ϭ 1.92 ("quint", "J" ϭ 7.3 Hz, 2 H), 2.15 ("quint",
"J" ϭ 7.7 Hz, 2 H), 2.22 (s, br, 1 H, –OH), 2.60 (t, J ϭ 6.9 Hz, 2
H), 3.40 (t, J ϭ 7.5 Hz, 2 H), 4.72 (s, 2 H), 6.84 (s, 1 H, 5-H), 7.20
("td", "J" ϭ 7.6, 1.3 Hz, 1 H), 7.29 ("td", "J" ϭ 7.7, 1.4 Hz, 1 H),
7.33 ("tt", "J" ϭ 8.5, 1.3 Hz, 2 H), 7.40 (ddd, J ϭ 7.6, 1.3, 0.6 Hz,
1 H), 7.48 (ddd, J ϭ 8.2, 7.2, 1.0 Hz, 1 H), 7.60–7.67 (m, 3 H),
8.00 (d, J ϭ 8.4 Hz, 1 H), 8.03 (ddd, J ϭ 8.2, 1.2, 0.6 Hz, 1 H),
8.81–8.83 (m, 1 H). – 13C NMR (126 MHz): δ ϭ 19.5 (t), 26.6 (t),
28.2 (t), 33.1 (t), 64.0 (t), 79.0 (s), 94.3 (s), 110.0 (d), 114.1 (d),
120.1 (d), 121.8 (s), 212.9 (d), 122.4 (s), 124.3 (d), 125.1 (d), 126.0
(d), 127.2 (d), 127.4 (d, 2C), 128.2 (d), 130.1 (d), 130.7 (s), 131.6
(s), 132.3 (d), 138.4 (s), 142.4 (s), 144.3 (s), 148.7 (s). – MS (70 eV);
m/z (%): 405 (17) [Mϩ ϩ 1], 404 (57) [Mϩ], 259 (20), 246 (24), 245
(100), 243 (15), 232 (46), 231 (17), 202 (9), 44 (10). – C28H24N2O
(404.5): calcd. C 83.14, H 5.98, N 6.93; found C 82.90, H 5.95,
N 6.92.
2-(2,4-Dimethoxyphenylethynyl)benzaldehyde (7.1f): From 1,3-di-
methoxy-4-ethynylbenzene[10] (6e; 0.31 g, 1.9 mmol) and 2-bromo-
benzaldehyde (5.1; 0.71 g, 3.8 mmol). A quarter of the amount of
reagents from the general procedure was used. TLC of the crude
product (silica, petroleum ether/methyl tert-butyl ether 3:1): Rf ϭ
0.57, 0.41, 0.32, 0.13. The fraction with Rf ϭ 0.32 was isolated by
flash chromatography and dried in vacuo (10 mbar, 50 °C) to give
7.1f (0.28 g, 55%) as yellow needles with m.p. 93–95 °C. – IR (KBr):
ν˜ ϭ 2940 cm–1 (w), 2840 (w), 2211 (m), 1691 (s), 1608 (s), 1593 (s),
1568 (m), 1507 (m), 1467 (m), 1437 (w), 1323 (w), 1302 (m), 1288
(m), 1268 (m), 1253 (w), 1212 (s), 1165 (m), 1119 (w), 1033 (m),
762 (w). – UV/Vis (acetonitrile): λmax (lg ε) ϭ 203 nm (4.59), 220
Oxidative Cyclization Reactions of 2-Alkynylbenzaldehydes with
ortho-Phenylene Diamine (2). – General Procedure: A solution of
100–500 mg of 2-alkynylbenzaldehyde 1 or 7 and 1–2 equivalents
of ortho-phenylenediamine (2) in 50 mL of nitrobenzene was heated
at 150 °C for 2 d. The solvent was then removed by distillation in
vacuo and the residue fractionated by flash chromatography.
1,4-Bis(6-benzimidazo[2,1-a]isoquinolinyl)butane (4): From bis(ben-
(4.52), 258 (4.47), 288 (4.27), 304 (4.26, sh), 312 (4.35), 348 (4.18). – zaldehyde) 1 (500 mg, 1.59 mmol) and ortho-phenylenediamine (2;
1H NMR (500 MHz): δ ϭ 3.84 (s, 3 H), 3.91 (s, 3 H), 6.48 (d, J ϭ 344 mg, 3.18 mmol). TLC of the crude product (silica, petroleum
2.4 Hz, 1 H, 3Ј-H), 6.50 (dd, J ϭ 8.4, 2.4 Hz, 1 H, 5Ј-H), 7.40 ("tt",
"J" ϭ 7.6, 0.9 Hz, 1 H), 7.44 (d, J ϭ 8.5 Hz, 1 H, 6Ј-H), 7.56 ("td",
ether/acetic acid ethyl ester 1:1): Rf ϭ 0.79, 0.51, 0.45. The fraction
with Rf ϭ 0.45 was isolated by flash chromatography and dried in
Eur. J. Org. Chem. 2000, 1433Ϫ1441
1437

G. Dyker, W. Stirner, G. Henkel
FULL PAPER
vacuo (0.1 mbar, 50 °C) to give 4 (363 mg, 47%) as a yellow solid
which starts decomposing above 280 °C. – IR (KBr): ν˜ ϭ 3053
cm–1 (w), 2937 (w), 2865 (w), 1642 (m), 1607 (w), 1558 (w), 1526
7.65 (m, 1 H, Ph-H), 7.68–7.70 (m, 2 H), 7.70–7.74 (m, 1 H), 7.99
(d, J ϭ 8.2 Hz, 1 H, 11-H), 8.89 (dd, J ϭ 6.0, 3.4 Hz, 1 H, 1-H). –
13C NMR (126 MHz): δ ϭ 112.6 (d, C-5), 114.1 (d, C-8), 119.7 (d,
(s), 1473 (w), 1452 (s), 1432 (m), 1401 (w), 1333 (m), 1293 (w), C-11), 121.3 (d, C-9), 122.9 (s), 124.2 (d, C-10), 125.1 (d, C-1),
1275 (w), 1237 (w), 1180 (w), 822 (w), 751 (m), 733 (s). – UV/Vis 126.7 127.91 (d), 129.0 (d, 2C), 129.4 (d, 2C), 129.9 (d), 130.1 (d),
(dichloromethane): λmax (lg ε) ϭ 236 nm (4.74), 269 (4.92), 279 130.7 (s), 131.6 (s), 134.7 (s), 137.5 (s), 144.3 (s), 148.3 (s). – MS
(5.01), 309 (4.22), 339 (4.14), 357 (4.10). – 1H NMR (500 MHz):
(70 eV); m/z (%): 295 (23) [Mϩ ϩ 1], 294 (100) [Mϩ], 293 (59), 292
δ ϭ 2.20 (s, br, 4 H), 3.40 (s, br, 4 H), 6.77 (s, 2 H), 7.34 (ddd, J ϭ (28), 147 (10) [M2ϩ], 147 (21), 146 (13). – C21H14N2 (294.4): calcd.
8.4, 7.2, 1.2 Hz, 2 H), 7.51 (ddd, J ϭ 8.1, 7.2, 0.9 Hz, 2 H), 7.61–
7.64 (m, 6 H), 7.94 (d, J ϭ 8.4 Hz, 2 H), 8.05 (d, J ϭ 7.8 Hz, 2 H),
8.82–8.84 (m, 2 H). – 13C NMR (126 MHz): δ ϭ 27.0 (t), 33.4 (t),
110.3 (d), 113.9 (d), 120.3 (d), 122.0 (d), 122.5 (s), 124.3 (d), 125.1
(d), 126.0 (d), 127.5 (d), 130.1 (d), 130.6 (s), 131.5 (s), 138.0 (s),
144.4 (s), 148.7 (s). – MS (70 eV); m/z (%):491 (24) [Mϩ ϩ 1], 490
(60) [Mϩ], 258 (13), 257 (15), 246 (23), 245 (100), 243 (20), 232
(17), 231 (27), 230 (11), 44 (32). – C34H26N4 (490.6): calcd. C 83.24,
H 5.34, N 11.42; found C 82.23, H 5.27, N 11.15; calcd. including
1.5 weight-% dichloromethane C 82.20, H 5.29, N 11.25. – HRMS:
calcd. 490.21576; found 490.21633.
C 88.69, H 4.79, N 9.52; found C 85.50, H 4.82, N 9.52.
The HBF4 salt 10.1b was formed by adding a few drops of tetra-
fluoroboric acid–diethyl ether complex to an analytical sample of
8.1b in dichloromethane. The grey precipitate was filtered off and
recrystallized from methanol/diethyl ether to give colourless crys-
tals of 10.1b which started to decompose at 200 °C (complete melt-
ing at 265 °C) and were suitable for X-ray structure analysis. – UV/
Vis (methanol): λmax (lg ε) ϭ 230 nm (4.55), 272 (4.60, sh), 280
(4.71), 311 (4.00), 320 (3.96, sh), 335 (3.92), 352 (3.81). – 1H NMR
(500 MHz, [D6]DMSO): δ ϭ 6.44 (d, J ϭ 8.6 Hz, 1 H, 8-H), 7.32
(ddd, J ϭ 8.5, 7.4, 1.0 Hz, 1 H), 7.67 ("td", "J" ϭ 7.5, 0.6 Hz, 1
H), 7.73–7.82 (m, 6 H), 8.00–8.04 (m, 2 H), 8.07 ("td", "J" ϭ 7.7,
1.1 Hz, 1 H), 8.21 (d, J ϭ 7.7 Hz), 8.82 (d, J ϭ 8.0 Hz, 1 H, 1-
H). – 13C NMR (126 MHz, [D6]DMSO): δ ϭ 114.9 (d), 115.2 (d),
116.6 (d), 117.0 (s), 124.1 (d), 124.6 (d), 127.5 (d), 128.0 (d), 128.5
(s), 129.4 (d, 2C), 129.6 (d, 2C), 129.7 (d), 130.9 (d), 132.7 (s), 133.0
(s), 133.2 (s, br), 133.6 (d), 136.7 (s), 143.8 (s).
6-n-Butylbenzimidazo[2,1-a]isoquinoline (8.1a): From 2-alkynylbenz-
aldehyde 7.1a (0.50 g, 2.7 mmol) and ortho-phenylenediamine (2;
0.29 g, 2.7 mmol). TLC of the crude product (silica, petroleum
ether/methyl tert-butyl ether 3:1): Rf ϭ 0.81, 0.65, 0.43. The frac-
tion with Rf ϭ 0.43 was isolated by flash chromatography and dried
in vacuo (0.1 mbar, 50 °C) to give 8.1a (337 mg, 46%) as bright
yellow needles with m.p. 133–135 °C.[11] – IR (KBr): ν˜ ϭ 3058
cm–1 (w), 2954 (m), 2934 (m), 2869 (w), 1641 (w), 1524 (s), 1466
(w), 1451 (s), 1430 (m), 1328 (w), 1275 (w), 1178 (w), 830 (m), 755
(m), 736 (s). – UV/Vis (acetonitrile): λmax (lg ε) ϭ 203 nm (4.92,
sh), 234 (4.75, sh), 258 (4.63), 267 (4.75), 277 (4.85), 324 (4.50), 356
Crystal Structure Determination of 10.1b: Siemens P4RA four-circle
˚
diffractometer, Mo-Kα radiation (λ ϭ 0.71073 A), graphite mono-
chromator, rotating anode generator, scintillation counter, 150 K,
empirical absorption corrections, SHELXL97 programs, direct
methods, least-squares refinements on F2, one scaling factor, one
isotropic extinction parameter. Crystal data: monoclinic, space
1
(3.87). – H NMR (500 MHz): δ ϭ 1.03 (t, J ϭ 7.4 Hz, 3 H, 4Ј-
H), 1.59 ("hex", "J" ϭ 7.4 Hz, 2 H, 3Ј-H), 1.88 ("quint", "J" ϭ
7.7 Hz, 2 H, 2Ј-H), 3.28 (t, J ϭ 7.4 Hz, 2 H, 1Ј-H), 6.75 (d, J ϭ
0.6 Hz, 1 H, 5-H), 7.36 (ddd, J ϭ 8.5, 7.2, 1.3 Hz, 1 H, 9-H), 7.49
(ddd, J ϭ 8.2, 7.1, 1.0 Hz, 1 H, 10-H), 7.58–7.64 (m, 3 H, 2-H, 3-
H, 4-H), 7.96 ("dt", "J" ϭ 8.5, 0.8 Hz, 1 H, 8-H), 8.04 (ddd, J ϭ 8.2,
1.2, 0.6 Hz, 1 H, 11-H), 8.80–8.83 (m, 1 H, 1-H). – NOE difference
experiment; spin saturation at δ ϭ 6.75 (5-H): δ ϭ 1.03 (ϩ0.4%,
4Ј-H), 1.59 (ϩ0.8%, 3Ј-H), 1.88 (ϩ4.6%, 2Ј-H), 3.28 (ϩ3.5%, 1Ј-
H) 7.58–7.64 (ϩ10.0%, 4-H). – 13C NMR (126 MHz): δ ϭ 14.0 (q,
C-4Ј), 22.4 (t, C-3Ј), 29.4 (t, C-2Ј), 33.1 (t, C-1Ј), 109.6 (d, C-5),
114.2 (d, C-8), 120.0 (d, C-11), 121.73 (d, C-9), 122.28 (s), 124.12
(d, C-10), 124.98 (d, C-1), 125.90 (d), 127.13 (d), 129.9 (d), 130.7
(s), 131.7 (s), 139.0 (s), 144.3 (s), 148.6 (s). – MS (70 eV); m/z (%):
275 (20) [Mϩ ϩ 1], 274 (90) [Mϩ], 245 (7), 243 (8), 233 (17), 232
(100), 231 (54), 230 (16), 229 (15). – C19H18N2 (274.4): calcd. C
83.18, H 6.61, N 10.21; found C 83.01, H 6.66, N 10.19.
˚
group P21/n, a ϭ 8.559(1), b ϭ 12.955(2), c ϭ 15.546(3) A, β ϭ
3
94.22(1)°, V ϭ 1719.1 A , Z ϭ 4, ρcalcd. ϭ 1.477 gcm–3, µ(Mo-
˚
Kα) ϭ 0.117 mm–1, transmission range 0.981–0.966, crystal dimen-
sions ca. 0.56 0.19 0.17 mm, ω-scan, 2Θmax ϭ 54°, 3993 independ-
ent reflections, R (Rw) ϭ 0.0368 (0.0884) for 3745 observed
reflections [I Ͼ 2σ(I)], 264 variables, all heavy atoms anisotropic,
H atoms at idealised positions.
6-(2-Pyridyl)-benzimidazo[2,1-a]isoquinoline (8.1c) and its HBF4
Salt: From 2-alkynylbenzaldehyde 7.1c (0.19 g, 0.93 mmol) and
ortho-phenylenediamine (2; 0.10 g, 0.93 mmol). TLC of the crude
product (silica, petroleum ether/acetic acid ethyl ester 1:1): Rf ϭ
0.76, 0.61, 0.53, 0.39. The fraction with Rf ϭ 0.39 was isolated by
flash chromatography and dried in vacuo (0.1 mbar, 50 °C) to give
8.1c (103 mg, 38%) as a slightly impure yellow oil. – 1H NMR
(500 MHz): δ ϭ 6.40 ("dt", "J" ϭ 8.4, 0.9 Hz, 1 H, 8-H), 7.03 (dd,
J ϭ 7.1, 1.1 Hz, 1 H), 7.04 (s, 1 H, 5-H), 7.39 (ddd, J ϭ 8.2, 7.2,
1.2 Hz, 1 H), 7.56 (ddd, J ϭ 7.7, 4.9, 1.2 Hz, 1 H), 7.66–7.77 (m,
3 H), 7.70 ("dt", "J" ϭ 7.7, 1.0 Hz, 1 H), 7.96 (dd, J ϭ 7.7, 1.8 Hz,
1 H), 7.99 ("dt", "J" ϭ 7.9, 0.9 Hz, 1 H), 8.86 (ddd, J ϭ 4.9, 1.8,
0.9 Hz, 1 H), 8.87–8.89 (m, 1 H).
6-Phenylbenzimidazo[2,1-a]isoquinoline (8.1b) and Its HBF4 Salt
10.1b: From 2-alkynylbenzaldehyde 7.1b (0.50 g, 2.4 mmol) and
ortho-phenylenediamine (2; 0.26 g, 2.4 mmol). TLC of the crude
product (silica, petroleum ether/methyl tert-butyl ether 3:1): Rf ϭ
0.61, 0.39, 0.30, 0.27, 0.15. The fraction with Rf ϭ 0.27 was isolated
by flash chromatography and dried in vacuo (0.1 mbar, 50 °C) to Since the free base 8.1c was difficult to purify, the complete charac-
give 8.1b (592 mg, 83%) as bright yellow needles with m.p. 185–187 terisation was done with its HBF4 salt. Upon treatment of a solu-
°C.[11] – IR (KBr): ν˜ ϭ 3067 cm–1 (w), 3022 (w), 1640 (w), 1527 tion of 8.1c in dichloromethane with tetrafluoroboric acid–diethyl
(m), 1493 (w), 1449 (s), 1394 (w), 1332 (m), 1311 (m), 1276 (m), ether complex the salt 10.1c HBF4 precipitated; obviously, 8.1c was
1235 (m), 1160 (w), 835 (m), 766 (m), 760 (m), 748 (s), 738 (s). – protonated twice, at N-12 and at the pyridine nitrogen. Recrystal-
UV/Vis (acetonitrile): λmax (lg ε) ϭ 203 nm (4.77, sh), 230 (4.66), lization from methanol/methyl tert-butyl ether gave analytically
260 (4.53, sh), 270 (4.64, sh), 283 (4.76), 322 (4.24), 354 (3.86). – pure 10.1c HBF4 as yellow crystals which started to decompose at
1H NMR (500 MHz): δ ϭ 6.49 (d, J ϭ 8.5 Hz, 1 H, 8-H), 6.91 (s, 148 °C (complete melting at 272 °C). – IR (KBr): ν˜ ϭ 3089 cm–1
1 H, 5 H), 7.00 (ddd, J ϭ 8.4, 7.3, 1.2 Hz, 1 H, 9-H), 7.39 (ddd, (m), 2900 (m), 1626 (s), 1564 (m), 1539 (m), 1486 (w), 1462 (m),
J ϭ 8.2, 7.2, 1.0 Hz, 1 H, 10 H), 7.60–7.61 (m, 4 H, Ph-H), 7.61– 1296 (w), 1255 (w), 1240 (w), 1174 (w), 1082 (vs), 1056 (vs), 1014
1438
Eur. J. Org. Chem. 2000, 1433Ϫ1441

Oxidative Heterocyclization of 2-Alkynylbenzaldehydes with 1,2-Phenylenediamine
(s), 962 (w), 776 (s), 751 (vs), 695 (m), 609 (m), 522 (w). – UV/Vis (d), 121.6 (d), 122.0 (d), 122.4 (d), 124.1 (s), 126.1 (s), 127.0 (d),
FULL PAPER
(methanol): λmax (lg ε) ϭ 230 nm (4.39), 273 (4.40), 314 (3.95), 334
127.9 (s), 128.3 (d), 128.6 (d), 128.7 (s), 129.6 (d), 135.6 (s), 143.2
(3.97), 350 (3.96), 377 (3.63, sh).
–
1H NMR (500 MHz,
(s), 148.0 (d). – MS (70 eV); m/z (%): 285 (21) [Mϩ ϩ 1], 284 (100)
[D6]DMSO/CDCl3 1:1): δ ϭ 6.47 ("dd", "J" ϭ 7.9, 0.7 Hz, 1 H), [Mϩ], 283 (24), 255 (17), 128 (10), 127.5 (6), 127.0 (9). –
7.31 (ddd, J ϭ 8.5, 7.3, 1.2 Hz, 1 H), 7.67 (ddd, J ϭ 8.3, 7.3, 1.0 Hz, C19H12N2O HBF4 (372.1): calcd. C 61.33, H 3.52, N 7.53; found C
1 H), 7.71 (ddd, J ϭ 7.7, 4.8, 1.1 Hz, 1 H), 7.83 (s, 1 H, 5-H), 7.91 61.23, H 3.67, N 7.61.
("dt", "J" ϭ 7.7, 1.0 Hz, 1 H), 7.94 ("dt", "J" ϭ 8.2, 0.9 Hz, 1 H),
7.99 (ddd, J ϭ 8.3, 7.2, 1.2 Hz, 1 H), 8.05 ("td", "J" ϭ 7.2, 1.2 Hz,
1 H), 8.13 (dd, J ϭ 7.7, 1.8 Hz, 1 H), 8.17 (d, J ϭ 7.9 Hz, 1 H),
An analytically pure sample of 10.1d 0.5(HBF4) was obtained from
the combined filtrates of the recrystallization procedure by the fol-
lowing steps: 1. treating the combined filtrates with aqueous NaOH
solution to give a mixture of the bases, this time enriched with
8.1d; 2. flash chromatography for further enrichment of 8.1d; 3.
formation of the HBF4 salt and crystallization from methanol/di-
ethyl ether to give 10.1d 0.5(HBF4) as slightly yellow crystals which
8.82 (ddd, J ϭ 4.8, 1.7, 0.9 Hz, 1 H), 8.84 ("d", "J" ϭ 8.1 Hz, 1
H). – 13C NMR (126 MHz, [D6]DMSO/CDCl3 1:1): δ ϭ 112.8 (d),
114.7 (d), 115.3 (s), 117.4 (d), 123.6 (d), 123.6 (d), 123.9 (d), 124.7
(d), 126.6 (s), 127.0 (d), 127.2 (d), 129.3 (d), 130.4 (s), 131.7 (s),
133.0 (d), 134.0 (s), 137.2 (d), 141.8 (s), 148.7 (d), 149.2 (s). – MS
started to decompose at 170 °C (complete melting at 256 °C).[11]
–
(70 eV); m/z (%): 296 (24) [Mϩ ϩ 1], 295 (94) [Mϩ], 294 (100) [Mϩ
–
IR (KBr): ν˜ ϭ 3145 cm–1 (w), 1654 (w), 1619 (w), 1590 (w), 1553
(s), 1493 (m), 1464 (m), 1084 (vs), 973 (m), 919 (w), 894 (w), 761
(s), 749 (s). – UV/Vis (acetonitrile): λmax (lg ε) ϭ 222 nm (4.35),
1], 293 (25) [Mϩ – 2], 147.8 (15) [M2ϩ], 147.2 (18) [M2ϩ – 1], 146.8
(7) [M2ϩ – 2], 49/48 (17)/(4) [BF2ϩ]. – C20H13N3 2(HBF4) (471.0):
calcd. C 51.01, H 3.21, N 8.92; found C 51.12, H 3.25, N 9.02.
1
232 (4.31, sh), 284 (4.54), 314 (3.84), 332 (3.77), 348 (3.60). – H
NMR (500 MHz, [D6]DMSO): δ ϭ 6.46 (d, J ϭ 8.4 Hz, 1 H, 8-
H), 6.96 (dd, J ϭ 3.4, 1.9 Hz, 1 H, 4Ј-H), 7.18 (d, J ϭ 3.3 Hz, 1 H,
3Ј-H), 7.44 ("t", "J" ϭ 7.7 Hz, 1 H, 9 H), 7.66 ("t", "J" ϭ 7.5 Hz,
1 H, 10-H), 7.90 (s, 1 H, 5-H), 7.97 (dd, J ϭ 7.3, 1.5 Hz, 1 H, 2-
H), 7.99 (dd, J ϭ 7.5, 1.7 Hz, 1 H, 3-H), 8.02 (d, J ϭ 8.2 Hz, 1 H,
11-H), 8.17–8.19 (m, 2 H, 4-H, 5Ј H), 8.79 (dd, J ϭ 7.7, 1.6 Hz, 1
H, 1-H). – 13C NMR (126 MHz, [D6]DMSO): δ ϭ 112.5 (d, C-4Ј),
113.5 (d, C-8), 113.9 (d, C-3Ј), 116.6 (d), 117.9 (d, C-5), 119.8 (s),
123.8, (d, C-9), 124.7 (d, C-1), 125.8 (s), 126.5 (d, C-10), 128.2 (d),
128.6 (s), 130.1 (d), 131.7 (s), 132.5 (d), 144.8 (s), 145.1 (d). – MS
6-(2-Furyl)-benzimidazo[2,1-a]isoquinoline (8.1d), 6-(2-Furyl)-isoin-
dolo[2,1-a]quinoxaline (9.1d) and Their HBF4 Salts 10.1d and 11.1d:
From 2-alkynylbenzaldehyde 7.1d (0.50 g, 2.6 mmol) and ortho-
phenylenediamine (2; 0.28 g, 2.6 mmol). TLC of the crude product
(silica, petroleum ether/methyl tert-butyl ether 3:1): Rf ϭ 0.62, 0.40,
0.29, 0.22, 0.12. A combined fraction with Rf ϭ 0.40 and 0.29 was
isolated by flash chromatography and dried in vacuo (0.1 mbar, 50
°C) to give a 1:14.1 mixture of 8.1d and 9.1d (321 mg, 44%) as a
brown oil.
1
(70 eV); m/z (%):285 (20) [Mϩ ϩ 1], 284 (100) [Mϩ], 283 (31) [Mϩ
–
8.1d: H NMR (500 MHz): δ ϭ 6.53 ("dt", "J" ϭ 8.4, 0.9 Hz, 1 H,
8-H), 6.73 (dd, J ϭ 3.4, 1.9 Hz, 1 H, 4Ј-H), 6.84 (dd, J ϭ 3.3,
0.8 Hz, 1 H, 3Ј-H), 7.16 (s, 1 H, 5-H), 7.19 (ddd, J ϭ 8.4, 7.2,
1.2 Hz, 1 H), 7.45 (ddd, J ϭ 8.2, 7.1, 1.1 Hz, 1 H), 7.68–7.77 (m,
4 H), 8.00 (d, J ϭ 8.1 Hz, 1 H, 11-H), 8.88 ("d", "J" ϭ 7.7 Hz, 1
H, 1-H).
1], 255 (20), 128 (11), 49 (6). – C19H12N2O 1.5(HBF4) (416.0):
calcd. C 55.48, H 3.30, N 6.81; found C 55.64, H 3.34, N 6.74
6-(5-Methyl-2-furyl)isoindolo[2,1-a]quinoxaline (9.1e) and Its HBF4
Salt 11.1e: From 2-alkynylbenzaldehyde 7.1e (0.16 g, 0.74 mmol)
and ortho-phenylenediamine (2; 80 mg, 0.74 mmol). TLC of the
crude product (silica, petroleum ether/methyl tert-butyl ether 1:1):
9.1d: 1H NMR (500 MHz): δ ϭ 6.73 (dd, J ϭ 3.4, 1.8 Hz, 1 H, 4Ј-
H), 7.23 (d, J ϭ 3.4 Hz, 1 H, 3Ј-H), 7.29 (ddd, J ϭ 8.6, 6.6, 0.9 Hz,
1 H, 8-H), 7.38 ("dd", "J" ϭ 7.9, 7.0 Hz, 1 H, 9-H), 7.57 (m, 2 H),
7.79 ("t", "J" ϭ 0.9 Hz, 1 H, 5Ј-H), 7.87 (d, J ϭ 8.4 Hz, 1 H, 10-
H), 8.07 (d, J ϭ 7.9 Hz, 1 H, 7-H), 8.07–8.11 (m, 2 H), 8.50 (s, 1
H, 11-H). – 13C NMR (126 MHz): δ ϭ 107.9 (d), 111.9 (d), 112.5
(d), 114.9 (d), 116.4 (s), 119.3 (d), 121.3 (d), 121.4 (s), 123.4 (d),
124.5 (d), 125.7 (s), 127.1 (d), 127.1 (d), 127.3 (s), 130.1 (d), 137.4
(s), 143.6 (d), 144.2 (s), 151.7 (s).
1
Rf ϭ 0.62, 0.56, 0.35. According to the H NMR spectrum of the
crude product and based on the diagnostic signal at δ ϭ 8.9 (m, 1
H, 1-H) the ratio of 8.1e/9.1e was determined to be 9:91. The frac-
tion with Rf ϭ 0.35 was isolated by flash chromatography and dried
in vacuo (0.1 mbar, 50 °C) to give 9.1e (110 mg, 50%) as a slightly
1
impure oily solid. – H NMR (500 MHz): δ ϭ 2.54 (t, J ϭ 0.5 Hz,
3 H), 6.31 (m, 1 H), 7.13 (d, J ϭ 0.8 Hz, 1 H), 7.30 ("td", "J" ϭ
6.4, 1.1 Hz, 1 H), 7.36–7.39 (m, 1 H), 7.55–7.57 (m, 2 H), 7.89 (d,
J ϭ 8.4 Hz, 1 H), 8.08–8.11 (m, 2 H), 8.23 (dd, J ϭ 8.7, 0.8 Hz, 1
H), 8.52 (s, 1 H, 11-H). – 13C NMR (126 MHz): δ ϭ 14.1 (q), 107.9
(d), 108.2 (d), 114.1 (d), 114.9 (d), 116.2 (s), 119.4 (d), 121.5 (s),
121.5 (d), 123.3 (d), 124.5 (d), 125.7 (s), 126.9 (d), 127.1 (d), 127.3
(s), 129.9 (d), 137.4 (s), 144.5 (s), 149.8 (s), 154.1 (s).
Since the free bases 8.1d and 9.1d were difficult to separate and to
purify the complete characterisation was done with their HBF4
salts. Upon treatment of a solution of 8.1d and 9.1d in dichlorome-
thane with tetrafluoroboric acid–diethyl ether complex, the precip-
itate was recrystallized from dichloromethane/petroleum ether in
several fractions to give analytically pure yellow crystals of 11.1d
which started to decompose at 185 °C (complete melting at 255–
260 °C).[11] – IR (KBr): ν˜ ϭ 3279 cm–1 (m), 3218 (w), 3131 (m),
Since the free base 9.1e was difficult to obtain with analytical purity
the complete characterisation was done with its HBF4 salt 11.1e.
Upon treatment of a sample of 9.1e in dichloromethane with tetra-
1618 (s), 1601 (m), 1551 (w), 1526 (w), 1510 (m), 1471 (w), 1453 fluoroboric acid–diethyl ether complex, the precipitate was recrys-
(m), 1429 (m), 1397 (w), 1383 (w), 1330 (s), 1237 (w), 1116 (m), tallized from dichloromethane/petroleum ether to give analytically
1083 (vs), 1056 (vs), 1030 (vs), 901 (w), 822 (w), 801 (w), 767 (s), pure brown crystals of 11.1e which started to decompose at 180 °C
745 (m). – UV/Vis (acetonitrile): λmax (lg ε) ϭ 205 nm (4.48), 230
(complete melting at 255 °C) and were suitable for an X-ray struc-
(4.52), 255 (4.54), 276 (4.39), 287 (4.35), 314 (4.27, sh), 324 (4.34), ture analysis.[11] – IR (KBr): ν˜ ϭ 3085 cm–1 (w), 1626 (m), 1598
364 (4.00, sh), 380 (4.11), 414 (4.05). – 1H NMR (500 MHz,
[D6]DMSO): δ ϭ 7.09 (dd, J ϭ 3.5, 1.8 Hz, 1 H), 7.63–7.66 (m, 2
(m), 1561 (s), 1522 (m), 1507 (s), 1472 (w), 1451 (s), 1426 (m), 1373
(s), 1331 (m), 1320 (w), 1124 (vs), 1084 (vs), 802 (w), 756 (s), 533
H), 7.72 (d, J ϭ 3.5 Hz, 1 H), 7.80–7.83 (m, 2 H), 8.02–8.04 (m, 1 (w). – UV/Vis (acetonitrile): λmax (lg ε) ϭ 231 nm (4.45), 249 (4.42),
H), 8.06–8.08 (m, 1 H), 8.15–8.17 (m, 1 H), 8.41 (d, J ϭ 1.5 Hz, 276 (4.30), 286 (4.23), 328 (4.25), 367 (4.01, sh), 382 (4.11), 415
1
1 H), 8.65–8.67 (m, 1 H), 9.79 (s, 1 H). – 13C NMR (126 MHz, (3.99, sh). – H NMR (500 MHz, [D6]DMSO): δ ϭ 2.60 (s, 3 H, –
[D6]DMSO): δ ϭ 113.4 (d), 115.1 (s), 117.2 (d), 118.7 (d), 120.7
Eur. J. Org. Chem. 2000, 1433Ϫ1441
CH3), 6.72 (d, J ϭ 2.9 Hz, 1 H, 4Ј H), 7.66 (m, 2 H), 7.79 ("dd",
1439

G. Dyker, W. Stirner, G. Henkel
"J" ϭ 6.1, 3.4 Hz, 2 H), 7.82 (d, J ϭ 3.4 Hz, 1 H), 8.17 (d, J ϭ 2.5 Hz, 1 H, 1-H), 9.88 (s, br, 1 H, OH). – 13C NMR (126 MHz,
FULL PAPER
7.9 Hz, 1 H), 8.26 ("dd", "J" ϭ 6.3, 3.2 Hz, 1 H), 8.30 (d, J ϭ
8.3 Hz, 1 H), 8.67 ("dd", "J" ϭ 6.2, 3.3 Hz, 1 H), 9.80 (s, 1 H, 11-
[D6]DMSO): δ ϭ 108.3 (d), 112.0 (d), 113.6 (d), 118.9 (d), 119.8
(d), 120.4 (d), 123.3 (d), 123.7 (s), 123.9 (s), 128.1 (d), 128.5 (d,
H). – 13C NMR (126 MHz, [D6]DMSO/CDCl3 1:1): δ ϭ 13.7 (q), 2C), 129.0 (d, 2C), 129.2 (d), 130.1 (s), 133.7 (s), 134.2 (s), 143.6
109.8 (d, C-4Ј), 114.4 (s), 116.8 (d, C-1), 120.5 (d), 120.6 (d, C-4),
(s), 147.2 (s), 157.1 (s). – MS (70 eV); m/z (%): 311 (23) [Mϩ ϩ 1],
120.7 (d, C-7), 121.9 (d, C-10), 123.0 (d, C-11), 123.5 (s), 126.7 (s), 310 (100) [Mϩ], 309 (31) [Mϩ – 1], 280 (9), 155.1 (6), [M2ϩ], 154.6
126.9 (d), 127.0 (s), 128.2 (d), 128.5 (d), 128.9 (s), 129.3 (d), 134.6
(7) [M2ϩ – 1], 140 (10). – C21H14N2 (310.4): calcd. C 81.27, H 4.55,
(s), 140.7 (s), 158.3 (s). – MS (70 eV); m/z (%): 299 (42) [Mϩ ϩ 1], N 9.03; found C 81.04, H 4.50, N 9.02.
298 (100) [Mϩ], 297 (36) [Mϩ – 1], 283 (8) [Mϩ – CH3], 255 (12),
Oxidative Cyclization of 2Ј-Formyl-trans-stilbene (16) with ortho-
149.5 (3) [(M ϩ 1)2ϩ], 149.0 (14) [M2ϩ], 49 (9) [BF2ϩ]. –
Phenylenediamine (2): A solution of 2Ј-formyl-trans-stilbene (16;
500 mg, 2.40 mmol) and ortho-phenylenediamine (2; 260 mg,
2.40 mmol) in nitrobenzene (50 mL) was heated at 150 °C for 2 d
after which time the solvent was removed in vacuo. The residue
C20H14N2O HBF4 (386.2).
Crystal Structure Determination of 11.1e: Crystal Data: triclinic,
˚
¯
space group P1, a ϭ 7.870(3), b ϭ 10.955(3), c ϭ 11.129(4) A, α ϭ
3
˚
65.36(2), β ϭ 77.17(2), γ ϭ 80.28(2) °, V ϭ 847.2 A , Z ϭ 2, was fractionated by flash chromatography; TLC (silica, petroleum
ρ
calcd. ϭ 1.514 gcm–3, µ(Mo-Kα) ϭ 0.124 mm–1, transmission range
ether/methyl tert-butyl ether 1:1): Rf ϭ 0.63, 0.48, 0.35–0.32. First
0.973–0.893, crystal dimensions ca. 0.65 0.22 0.19 mm, ω-scan, fraction benzimidazoisoquinoline 8.1b (22 mg, 3%; Rf ϭ 0.48). The
2Θmax ϭ 54°, 3975 independent reflections, R (Rw) ϭ 0.0659 second fraction with Rf ϭ 0.35–0.32 was crystallized from dichloro-
(0.1740) for 3699 observed reflections [I Ͼ 2σ(I)], 254 variables, all
heavy atoms anisotropic, H atoms at idealised positions.
methane/petroleum ether to give benzimidazole 17 (327 mg, 46%;
Rf ϭ 0.35) as a colourless solid which starts to decompose at 185
°C (complete melting at 215 °C). – IR (KBr): ν˜ ϭ 3057 cm–1 (m),
3023 (m), 2922 (m), 2878 (m), 2791 (m), 2729 (m), 2683 (m), 1618
(w), 1598 (w), 1539 (w), 1491 (m), 1444 (s), 1417 (m), 1316 (w),
1270 (m), 1220 (w), 968 (m), 954 (m), 750 (vs), 742 (s), 693 (m). –
UV/Vis (acetonitrile): λmax (lg ε) ϭ 203 nm (4.78), 283 (4.55), 310
(4.44), 433 (2.07). – 1H NMR (500 MHz, [D6]DMSO, somewhat
broad signals): δ ϭ 7.21–7.28 (m, 3 H), 7.29 (d, J ϭ 16.7 Hz, 1 H),
7.37 ("t", "J" ϭ 7.7 Hz, 2 H), 7.48 ("td", "J" ϭ 7.5, 0.9 Hz, 1 H),
7.51–7.56 (m, 4 H), 7.74 (d, J ϭ 7.5 Hz, 1 H), 7.80 (dd, J ϭ 7.7,
1.0 Hz, 1 H), 7.98 (d, J ϭ 7.9 Hz, 1 H), 8.05 (d, J ϭ 16.4 Hz, 1
H). – 1H NMR (500 MHz, [D6]DMSO ϩ 1 drop of CF3COOH,
6-(2,4-Dimethoxyphenyl)-benzimidazo[2,1-a]isoquinoline
(8.1f):
From 2-alkynylbenzaldehyde 7.1f (0.10 g, 0.38 mmol) and ortho-
phenylenediamine (2; 41 mg, 0.38 mmol). TLC of the crude prod-
uct (silica, petroleum ether/methyl tert-butyl ether 1:1): Rf ϭ 0.53,
0.41, 0.31, 0.21, 0.03. The fraction with Rf ϭ 0.21 was isolated by
flash chromatography and dried in vacuo (0.1 mbar, 50 °C) to give
8.1f (86 mg, 64%) as bright yellow crystals which started to decom-
pose at 185 °C (complete melting at 195 °C). – IR (KBr): ν˜ ϭ 3059
cm–1 (w), 3004 (w), 2937 (w), 2839 (w), 1641 (m), 1609 (s), 1578
(m), 1526 (m), 1502 (s), 1450 (s), 1416 (w), 1308 (m), 1279 (m),
1262 (w), 1234 (w), 1210 (s), 1164 (s), 1130 (w), 1037 (m), 841 (w),
756 (m), 743 (m). – UV/Vis (acetonitrile): λmax (lg ε) ϭ 199 nm
(4.69), 222 (4.52), 261 (4.34, sh), 272 (4.52, sh), 284 (4.66), 314
sharp signals): δ ϭ 7.26 ("t", "J" ϭ 7.3 Hz, 1 H), 7.33 ("t", "J"[1]
ϭ
7.6 Hz, 2 H), 7.39 (d, J ϭ 12.8 Hz, 1 H), 7.55 (d, J ϭ 7.5 Hz, 2 H),
7.59 (dd, J ϭ 6.1, 3.3 Hz, 2 H), 7.74 ("t", "J" ϭ 7.5 Hz, 1 H), 7.83
(dd, J ϭ 7.7, 1.1 Hz, 1 H), 7.86 (dd, J ϭ 6.1, 3.1 Hz, 2 H), 8.08 (d,
J ϭ 8.0 Hz, 1 H). – 13C NMR (126 MHz, [D6]DMSO ϩ 1 drop of
CF3COOH): δ ϭ 114.7 (d, 2C), 122.6 (s), 124.6 (d), 126.5 (d, 2C),
127.2 (d), 127.6 (d, 2C), 128.4 (d), 128.8 (d), 129.1 (d, 2C), 132.1
(d), 132.3 (s, 2C), 133.3 (d), 133.8 (d), 137.1 (s), 137.1 (s), 149.4
(s). – MS (70 eV); m/z (%): 297 (4) [Mϩ ϩ 1], 296 (20) [Mϩ], 295
(9), 220 (17), 219 (100), 218 (11), 147 (4).
1
(3.92, sh), 337 (3.86), 355 (3.72). – H NMR (500 MHz): δ ϭ 3.56
(s, 3 H), 3.96 (s, 3 H), 6.64 (d, J ϭ 2.3 Hz, 1 H, 3Ј-H), 6.66 (d, J ϭ
8.5 Hz, 1 H, 8-H), 6.69 (dd, J ϭ 8.3, 2.3 Hz, 1 H, 5Ј-H), 6.90 (s, 1
H, 5-H), 7.04 (ddd, J ϭ 8.4, 7.2, 1.2 Hz, 1 H), 7.38 (dd, J ϭ 8.1,
1.0 Hz, 1 H), 7.39 (d, J ϭ 8.3 Hz, 1 H, 6Ј-H), 7.66–7.67 (m, 2 H),
7.71–7.73 (m, 1 H), 7.98 (dd, J ϭ 8.2, 0.6 Hz, 1 H), 8.88–8.90 (m,
1 H, 1-H). – 13C NMR (126 MHz): δ ϭ 55.6 (q), 55.6 (q), 98.9 (d),
104.6 (d), 113.0 (d), 113.3 (d), 116.7 (s), 119.5 (d), 121.4 (d), 123.0
(s), 123.9 (d), 125.1 (d), 126.6 (d), 127.6 (d), 129.9 (d), 131.2 (s), The filtrate of the crystallization process was concentrated and the
131.8 (s), 131.9 (d), 134.9 (s), 144.0 (s), 148.2 (s), 159.3 (s), 162.6
residue purified again by flash chromatography to give slightly im-
(s). – MS (70 eV); m/z (%): 355 (27) [Mϩ ϩ 1], 354 (100) [Mϩ], 353 pure 5,6-dihydro-6-phenylbenzimidazo[2,1-a]isoquinoline (18;
(11) [Mϩ – 1], 339 (11), 324 (7), 267 (9), 177 (5), 140 (7). – 183 mg, 26%; Rf ϭ 0.32). – 1H NMR (500 MHz): δ ϭ 3.36 (dd,
C23H18N2O2 (294.4): calcd. C 77.95, H 5.12, N 7.81; found C 77.77,
H 5.12, N 7.90.
J ϭ 15.9, 3.6 Hz, 1 H, 5-Ha), 3.80 (dd, J ϭ 15.9, 6.8 Hz, 1 H, 5-
Hb), 5.77 (dd, J ϭ 6.8, 3.7 Hz, 1 H, 6-Ha), 6.96–6.98 (m, 2 H), 7.00
("dt", "J" ϭ 8.2, 0.9 Hz, 1 H), 7.14 (ddd, J ϭ 8.2, 7.2, 1.1 Hz, 1
H), 7.18 (d, J ϭ 7.5 Hz, 1 H), 7.20 7.22 (m, 3 H), 7.25 (ddd, J ϭ
8.2, 7.2, 1.1 Hz, 1 H), 7.34 ("td", "J" ϭ 7.5, 1.4 Hz, 1 H), 7.40 ("t",
"J" ϭ 7.5 Hz, 1 H), 7.84 ("dt", "J" ϭ 8.1, 0.9 Hz, 1 H), 8.36 (dd,
J ϭ 7.7, 1.0 Hz, 1 H).
2-Hydroxy-6-phenyl-benzimidazo[2,1-a]isoquinoline (8.2b): From 2-
alkynylbenzaldehyde 7.2b (234 mg, 1.05 mmol) and ortho-pheny-
lenediamine (2; 114 mg, 1.05 mmol). The crude product was recrys-
tallized from dichloromethane by adding a layer of petroleum ether.
After filtration and drying in vacuo (0.1 mbar, 50 °C) 8.2b (289 mg,
88%) was obtained as slightly coloured crystals which started to
decompose at 290 °C. – IR (KBr): ν˜ ϭ 3437 cm–1 (w), 3059 (w),
Because of the difficult purification of the free base, compound 18
was fully characterized as its HBF4 salt 18 HBF4: slightly green
2898 (w), 2733 (w), 2692 (w), 2606 (w), 1613 (m), 1597 (m), 1527 needles which start to decompose at 175 °C (complete melting at
(m), 1494 (m), 1452 (s), 1379 (w), 1349 (s), 1269 (m), 1256 (s), 1232 234–237 °C). – IR (KBr): ν˜ ϭ 3172 cm–1 (w), 1626 (w), 1613 (w),
(m), 855 (w), 766 (w), 739 (m), 699 (w). – UV/Vis (methanol): λmax 1584 (w), 1570 (w), 1515 (w), 1493 (w), 1463 (m), 1421 (w), 1332
(lg ε) ϭ 199 nm (4.69), 222 (4.52), 261 (4.34, sh), 272 (4.52, sh), 284 (w), 1184 (w), 1158 (m), 1083 (s), 970 (m), 754 (s), 725 (w),
(4.66), 314 (3.92, sh), 337 (3.86), 355 (3.72). – 1H NMR (500 MHz,
707 (w). – UV/Vis (methanol): λmax (lg ε) ϭ 243 nm (4.31), 250
[D6]DMSO): δ ϭ 6.39 (d, J ϭ 8.4 Hz, 1 H), 6.86 (s, 1 H, 5 H), 6.90 (4.25), 285 (4.27, sh), 295 (4.36), 308 (4.48), 322 (4.44). – 1H NMR
(ddd, J ϭ 8.5, 7.2, 1.3 Hz, 1 H), 7.18 (dd, J ϭ 8.5, 2.6 Hz, 1 H, 3- (500 MHz): δ ϭ 3.59 (dd, J ϭ 16.6, 2.8 Hz, 1 H, 5-Ha), 4.01 (dd,
H), 7.27 (ddd, J ϭ 8.2, 7.1, 1.0 Hz, 1 H), 7.55–7.59 (m, 5 H), 7.61 J ϭ 16.5, 7.3 Hz, 1 H, 5-Hb), 6.47 (dd, J ϭ 7.2, 2.8 Hz, 1 H, 6-Ha),
(d, J ϭ 8.5 Hz, 1 H), 7.79 (d, J ϭ 8.2 Hz, 1 H), 8.06 (d, J ϭ
7.10–7.11 (m, 2 H), 7.27–7.30 (m, 3 H), 7.50–7.53 (m, 2 H), 7.58–
1440
Eur. J. Org. Chem. 2000, 1433Ϫ1441

Oxidative Heterocyclization of 2-Alkynylbenzaldehydes with 1,2-Phenylenediamine
FULL PAPER
38, 6395–6396. –[4b] B. Yadagiri, J. W. Lown, Synth. Commun.
1990, 20, 955–963.
7.68 (m, 4 H), 7.94 (d, J ϭ 8.2 Hz, 1 H), 8.26 (dd, J ϭ 7.4, 1.3 Hz,
1 H). – 13C NMR (126 MHz): δ ϭ 34.7 (t, C-5), 54.8 (d, C-6), 112.3
(d), 115.1 (d), 120.1 (s), 125.9 (d), 125.9 (d, 2C), 126.1 (d), 126.3
(d), 128.2 (d), 128.5 (d), 129.0 (d, 2C), 129.6 (d), 131.3 (s), 132.6
(s, br), 134.0 (d), 134.7 (s), 137.6 (s), 146.1 (s). – MS (70 eV); m/z
(%): 297 (23) [Mϩ ϩ 1], 296 (100) [Mϩ], 295 (11), 220 (17) 219 (96),
218 (15), 148 (6), 77 (5). – C21H16N2 HBF4 (384.2): calcd. C 65.60,
H 4.46, N 7.29; found C 65.30, H 4.50, N 7.25.
[5]
[6]
S. Thorand, N. Krause, J. Org. Chem. 1998, 63, 8551–8553,
and references therein.
Crystallographic data (excluding structure factors) for the
structure(s) included in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publication nos. CCDC-138679 for 10.1b and CCDC-138680
for 11.1e. Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [Fax: (internat.) ϩ 44-1223/336-033; Email: deposit@-
ccdc.cam.ac.uk].
T. Sakamoto, Y. Kondo, N. Miura, K. Hayashi, H. Yamanaka,
Heterocycles 1986, 24, 2311–2314.
A. Carpita, R. Rossi, C. A. Veracini, Tetrahedron 1985, 41,
1919–1930.
[7]
[8]
[9]
Acknowledgments
Financial support by the Deutsche Forschungsgemeinschaft and by
the Fonds der Chemischen Industrie is gratefully acknowledged.
2-Ethynyl-5-methylfuran (6e) was synthesized from 5-methylfu-
ran-2-carbaldehyde in analogy to common literature proced-
ures: E. J. Corey, P. L. Fuchs, Tetrahedron Lett. 1972, 3769–
3772.
[1] [1a]
T. Sakamoto, Y. Kondo, N. Miura, K. Hayashi, H. Yam-
[1b]
anaka, Heterocycles 1986, 24, 2311–2314. –
Q. Sun, E. J.
[10] [10a]
LaVoie, Heterocycles 1996, 43, 737–743.
G. Dyker, W. Stirner, G. Henkel, M. Köckerling, Tetrahedron
Lett. 1999, 40, 7457–7458.
For redox processes during the reaction of ortho-phenylene di-
amine with benzaldehyde: J. G. Smith, I. Ho, Tetrahedron Lett.
1971, 3541–3544.
R. T. Scannell, R. Stevenson, J. Heterocycl. Chem. 1980,
[2]
[3]
[10b]
17, 1727–1728. –
Liebigs Ann. 1995, 1663–1672.
The NMR assignments are supported by the results of two-
L. Dulog, B. Koerner, J. Heinze, J. Yang,
[11]
dimensional NMR spectra including 1H-1H-COESY, 1H-13C-
COESY and H-1H-NOESY.
1
[4]
For related examples of nitrobenzene as oxidizing agent: [4a] A.
Ben-Alloum, S. Bakkas, M. Soufiaoui, Tetrahedron Lett. 1997,
Received September 10, 1999
[O99519]
Eur. J. Org. Chem. 2000, 1433Ϫ1441
1441