Bismuth(III) chloride catalyzed intramolecular hetero-diels-alder reaction: Access to cis -fused angular hexahydrobenzo[ c ]acridines

Article abstract of DOI:10.1055/s-0034-1379022

New polycyclic hexahydrobenzo[c]acridines were synthesized in excellent yields by intramolecular [4+2]-cycloaddition reactions of aldimines derived from aromatic amines and 2-(4-methylpent-3-en-1-yl)benzaldehyde in acetonitrile in the presence of 10 mol%

Full text of DOI:10.1055/s-0034-1379022

SYNTHESIS
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©
Georg Thieme Verlag Stuttgart · New York
2015, 47, 0124–0128
124
paper
Synthesis
G. Sabitha et al.
Paper
Bismuth(III) Chloride Catalyzed Intramolecular Hetero-Diels–Alder
Reaction: Access to cis-Fused Angular Hexahydrobenzo[c]acridines
cis-Fused Angular Hexahydrobenzo[c]acridines
Gowravaram Sabitha*
Kontham Shankaraiah
Kancherla Sindhu
R
NH2
CHO
BiCl3 (cat)
MeCN, r.t.
HN
H
Bejawada Madhavi Latha
+
R
H
Natural Products Chemistry Division, CSIR-Indian Institute of
Chemical Technology, Hyderabad 500 007, India
+
9
1
4
(
0
2
)
7
1
6
0
5
1
2
gowravaramsr@yahoo.com
sabitha@iict.res.in
Received: 23.04.2014
Accepted after revision: 04.08.2014
Published online: 06.10.2014
88% yield from 2-methylbenzaldehyde and 1-bromo-3-
methylbut-2-ene (prenyl bromide) in the presence of
N,N,N′-trimethylethane-1,2-diamine (Scheme 1).
6
DOI: 10.1055/s-0034-1379022; Art ID: ss-2014-z0258-op
Abstract New polycyclic hexahydrobenzo[c]acridines were synthe-
sized in excellent yields by intramolecular [4+2]-cycloaddition reactions
of aldimines derived from aromatic amines and 2-(4-methylpent-3-en-
CHO
CHO
1
. BuLi, Me2N(CH2)2NHMe, THF
. Me2C=CHCH2Br
1-yl)benzaldehyde in acetonitrile in the presence of 10 mol% of bis-
2
muth(III) chloride. The reaction is highly diastereoselective, giving cis-
1
fused benzoacridine derivatives preferentially.
Scheme 1 Preparation of 2-(4-methylpent-3-en-1-yl)benzaldehyde (1)
Key words hetero-Diels–Alder reactions, catalysis, heterocycles, poly-
cycles, aldimines, aldehydes
The use of bismuth trichloride in the cyclization of alde-
hyde 1 with amines has several advantages. Bismuth is the
The intramolecular hetero-Diels–Alder reaction1,2 has
become an attractive tool for the synthesis of complex mo-
lecular structures. Angularly fused polycyclic nitrogen het-
least toxic of the heavy elements
9a,b
and the biochemistry,
9c
toxicology,9 and environmental effects of bismuth com-
pounds have been reviewed. Moreover, bismuth com-
pounds are employed as catalysts in industry for the manu-
facture of acrolein and acrylonitrile, and they are also used
in pharmaceutical products.
d
9e
3
erocycles are of great importance to chemists and biolo-
gists because of the significant role played by such com-
pounds in biological systems and in medicinal chemistry.
Heterocyclic systems containing the hexahydroben-
zo[a]acridine skeleton can be prepared by cascade hetero-
cyclization of cyclic diketones with aromatic amines and
Having prepared aldehyde 1, we examined its intramo-
lecular [4+2]-cycloaddition reactions. Initially, we studied
the reaction of aldehyde 1 with aniline (2a) in the presence
of 10 mol% bismuth(III) chloride in acetonitrile at 85 °C, and
we obtained 7,7-dimethyl-5,6,6a,7,12,12a-hexahydroben-
zo[c]acridine (3a) in 82% yield (Scheme 2). The reaction was
complete in one hour, as indicated by thin-layer chromatog-
raphy. The reaction proceeds by generation of an imine that
undergoes an intramolecular hetero-Diels–Alder reaction to
give the product 3a as a mixture of cis- and trans-diastereo-
mers with the former as the predominant product. The ra-
tio of the cis- and trans-isomers of 3a was determined by
NMR spectroscopic studies on the crude product. In com-
pound 3a, the H-6a proton appears as a doublet of triplets
at δ = 1.83. This is the result of coupling of the H-6a proton
with the H-6′ proton, resulting in a doublet with a large J
value (J6a,6′ = 12.3 Hz) that is split into a triplet with a small J
4
vanillyl esters. Benzoacridine derivatives have been report-
ed to possess a significant inhibitory effect on the growth of
5
KB human papilloma cells, an activity that is creating in-
terest in further studies on such derivatives. To the best of
our knowledge, there have been no reported syntheses of
angularly fused hexahydrobenzoacridine derivatives from
6
2
-(4-methylpent-3-en-1-yl)benzaldehyde (1) and aromat-
ic amines. As a continuation of our work on [4+2] cycload-
7
dition chemistry, and on the basis of a report in the litera-
8
ture, we have developed a novel synthesis of angularly
fused benzoacridine derivatives by means of the intramo-
lecular hetero-Diels–Alder reaction of 2-(4-methylpent-3-
en-1-yl)benzaldehyde with aromatic amines in the pres-
ence of bismuth(III) chloride. Aldehyde 1 was prepared in
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 124–128

1
25
Synthesis
G. Sabitha et al.
Paper
value (3.4 Hz) by coupling with the equatorial H-12a and H-
protons. This corresponds to a cis-fusion at the junction.
The doublet for the H-12a proton appears at δ = 4.65 with a
small J value as a result of vicinal coupling with an equato-
rial H-6a proton (J12a,6a = 3.2 Hz). The cis-configuration of H-
Table 1 Synthesis of Angular Hexahydrobenzo[c]acridines 3a–k
6
R2
R1
R3
NH2
R1
BiCl3 (cat.)
MeCN, r.t.
CHO
6a and H-12a in compound 3 was confirmed by the strong
R4
+
HN
H
NOE peaks. Confirmation of the cis-fusion of 3a was also
R4
R2
obtained by direct comparison with data reported in the lit-
R3
H
H
7b,d,f
1
erature,
in addition to the H NMR spectral data.
H
1
0
1
2a–k
cis–3a–k
1
1
9
NH2
Entry R1
R2
R3
R4
Producta Yield (%) cis/transc
b
1
2
CHO
BiCl3 (cat.)
MeCN, r.t.
8
HN
+
1
H
7
1
2
3
4
5
6
7
8
9
1
H
H
H
H
3a
3b
3c
3d
3e
3f
82
80
85
82
75
77
74
86
82
87
80
96:4
95:5
96:4
95:5
96:4
95:5
93:7
96:4
93:7
97:3
94:6
1
2a
2
3
6
a
H
H
H
H
H
H
H
H
Br
H
Me
OMe
H
H
H
H6
1
2a
H
H
4
5
H
6
'
Cl
H
H
cis-3a
F
H
Scheme 2 Preparation of 7,7-dimethyl-5,6,6a,7,12,12a-hexahydro-
benzo[c]acridine (3a)
OH
H
H
H
NO
2
H
3g
3h
3i
In an effort to demonstrate the scope of the bismuth(III)
chloride-catalyzed hetero-Diels–Alder reaction, we exam-
ined the reactions of aldehyde 1 with several anilines 2b–k
bearing various substituents (Table 1). Amines bearing elec-
tron-donating groups and those bearing electron-with-
drawing groups both gave the corresponding products 3 in
high yields under similar reaction conditions to those used
for aniline (2a); the substituents had no obvious effect on
the yield or the reaction time under optimized conditions.
In all cases, the cis-annulated products were formed pre-
dominantly. The products were characterized by means of
IR, H and C NMR, and mass spectroscopy. Acetonitrile
was selected as the optimal solvent, as it gave better results
than other solvents tested such as methanol, tetrahydrofu-
ran, diethyl ether, dichloromethane, or 1,2-dichloroethane.
Mechanistically, the reaction proceeds through forma-
tion of an imine from the aromatic amine and 2-(4-methyl-
pent-3-en-1-yl)benzaldehyde (1). The imine then under-
goes a Lewis acid induced intramolecular hetero-Diels–
Alder reaction to give the hexahydrobenzo[c]acridine
Br
H
H
Br
Br
H
H
0
1
CO
H
2
H
OMe
OMe
3j
1
OMe
OMe
3k
a
All products were characterized by NMR and IR spectroscopy, and mass
spectrometry.
b
Yield of pure product after chromatography.
c
1
Ratio determined by H NMR spectroscopy on crude product.
conditions, short reaction times, and the use of a soft Lewis
acid catalyst that is commercially available. The method is
therefore highly practical and might find wide applicability
in organic synthesis.
1
13
All reagents and catalysts were purchased from Sigma-Aldrich. Reac-
tions were conducted under N in anhydrous solvents such as THF or
2
MeCN. All reactions were monitored by TLC on Merck 60 F-254 silica
gel plates visualized under UV radiation. Hexanes (bp 60–80 °C) and
EtOAc were used for silica gel column chromatography. Yields refer to
chromatographically and spectroscopically ( H and C NMR) homo-
geneous materials. Air-sensitive reagents were transferred by syringe.
Evaporation of solvents was performed at reduced pressure on a Bu-
chi rotary evaporator. H and C NMR spectra of samples in CDCl
were recorded on Bruker UXNMR FT-300 MHz (Avance) spectrome-
ters with TMS as an internal standard. Mass spectra were recorded on
1
13
(
Scheme 3).
In conclusion, we have demonstrated a convenient syn-
1
13
thesis of cis-fused hexahydrobenzo[c]acridines derivatives
in good yields in a one-pot operation using bismuth(III)
chloride. The advantages of the present protocol are mild
3
BiCl3
NH2
N
CHO
N
HN
BiCl3
H
+
H
Scheme 3 A plausible reaction mechanism
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 124–128

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Synthesis
G. Sabitha et al.
Paper
a Finnigan MAT 1020B or a Micromass VG 70–70 H spectrometer op-
erated at 70 eV with a direct inlet system. Column chromatography
was performed on silica gel (60–20 mesh; ACME Chemicals, Mumbai).
H), 4.22–4.11 (br s, 1 H), 2.93–2.89 (m, 1 H), 2.27 (s, 3 H), 2.08–2.03
(m, 1 H), 1.79–1.73 (m, 1 H), 1.59–1.50 (m, 2 H), 1.40 (s, 3 H), 1.23 (s,
3 H).
13
C NMR (75 MHz, CDCl ): δ = 137.7, 135.7, 132.2, 130.5, 129.1, 128.3,
3
2
-(4-Methylpent-3-en-1-yl)benzaldehyde (1)6
A solution of Me N(CH ) NHMe (1.1 mL, 9.8 mmol, 1.1 equiv) in THF
128.2, 127.3, 126.6, 126.3, 125.7, 116.0, 51.4, 46.9, 35.9, 30.9, 28.3,
27.9, 21.9, 17.6.
2
2 2
(
20 mL) at –20 °C was sequentially treated with a 1.6 M solution of
+
ESI-MS: m/z = 278 [M + H].
BuLi in hexanes (5.89 mL, 9.43 mmol, 1.05 equiv) and 2-MeC H CHO
6
4
+
HRMS: m/z [M + H] calcd for C20H24N: 278.1908; found: 278.1902.
(1.08 g, 8.98 mmol). After 15 min, a further 3 equivalents of BuLi were
added at –20 °C, Me C=CCH Br (5.4 mL, 35.95 mmol, 4 equiv) was
added at –78 °C, and the mixture was stirred for 30 min. The resulting
2
2
9
-Methoxy-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acri-
dine (3c)
mixture was then poured into cold sat. aq NH Cl (10 mL) and extract-
4
ed with EtOAc (3 × 20 mL). The extracts were combined, washed with
Colorless viscous liquid; yield: 249 mg (85%).
brine (2 × 10 mL), dried (Na SO ), and concentrated under reduced
pressure. The crude product was purified by flash column chromatog-
raphy [silica gel, hexane–EtOAc (15:1)] to give a colorless oil; yield:
2
4
IR (neat): 3423, 3063, 2959, 2933, 1612, 1512, 1474, 1228, 1037, 819
–1
cm
.
1
H NMR (300 MHz, CDCl ): δ = 7.38–7.13 (m, 4 H), 6.84–6.77 (m, 1 H),
3
1.48 g (88%).
6.64–6.55 (m, 1 H), 6.34 (d, J = 8.3 Hz, 1 H), 4.60 (d, J = 3.0 Hz, 1 H),
IR (neat): 3447, 2961, 2927, 2860, 1696, 1600, 1450, 1207, 757 cm–1
.
4.24 (s, 1 H), 3.75 (s, 3 H), 2.91–2.79 (m, 1 H), 2.68 (dd, J = 15.1, 7.5 Hz,
1
H NMR (300 MHz, CDCl ): δ = 10.27 (s, 1 H), 7.83 (dd, J = 7.7, 1.3 Hz, 1
1 H), 1.87–1.78 (m, 1 H), 1.71–1.46 (m, 2 H), 1.43 (m, 3 H), 1.37 (m, 3
3
H), 7.50 (td, J = 7.6, 1.3 Hz, 1 H), 7.36 (td, J = 7.6, 1.0 Hz, 1 H), 7.27 (d,
J = 8.2 Hz, 1 H), 5.20–5.15 (m, 1 H), 3.08–3.01 (m, 2 H), 2.30 (qt, J =
H).
13
C NMR (75 MHz, CDCl ): δ = 159.4, 141.0, 137.9, 130.4, 129.3, 128.1,
26.6, 126.5, 126.0, 114.8, 111.7, 111.3, 70.8, 55.7, 55.3, 40.8, 28.3,
25.6, 25.1, 17.6. 6.
3
1
5.1, 7.5 Hz, 2 H), 1.66 (s, 3 H), 1.45 (s, 3 H).
1
13
C NMR (75 MHz, CDCl ): δ = 191.9, 145.0, 133.6 (2 C), 131.1, 130.9,
3
1
26.4, 122.7, 32.3, 30.5, 25.6, 17.4. .
+
ESI-MS: m/z = 294 [M + H].
+
ESI-MS: m/z = 211 [M + Na].
+
HRMS: m/z [M + H] calcd for C20H24NO: 294.1857; found: 294.1859.
7
,7-Dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridines 3a–k;
1
1-Chloro-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acri-
General Procedure
dine (3d)
BiCl3 (10 mol%) was added to a mixture of the appropriate aromatic
amine 2a–k (1 mmol) and aldehyde 1 (1.1 mmol) in anhyd MeCN (5
mL), and the mixture was refluxed at 85 °C for 1 h. When the reaction
was complete (TLC), the mixture was filtered through Celite. The fil-
trate was extracted with EtOAc (3 × 20 mL), and the extracts were
combined, washed with brine (2 × 10 mL), dried (Na SO ), and con-
Pale yellow viscous liquid; yield: 243 mg (82%).
IR (neat): 3436, 3063, 2961, 2929, 2869, 1696, 1496, 1303, 1240, 771,
–
1
7
31 cm .
1
H NMR (300 MHz, CDCl ): δ = 7.48 (d, J = 7.7 Hz, 1 H), 7.33–7.27 (m, 1
3
H), 7.24–7.20 (m, 2 H), 7.17 (d, J = 7.5 Hz, 1 H), 7.12 (dd, J = 7.7, 1.2 Hz,
2
4
1
H), 6.6 (t, J = 7.7 Hz, 1 H), 5.01–4.96 (br s, 1 H), 4.36 (d, J = 10.5 Hz, 1
centrated. The crude product was purified by chromatography [silica
gel, hexanes–EtOAc (16:1)].
H), 2.73 (dd, J = 7.7, 2.8 Hz, 2 H), 2.09–2.03 (m, 1 H), 1.80–1.74 (m, 1
H), 1.62–1.55 (m, 1 H), 1.41 (s, 3 H), 1.23 (s, 3 H).
13C NMR (75 MHz, CDCl
1
1
): δ = 136.8, 131.2, 129.2, 128.1, 126.8, 126.5,
25.5 (2 C), 125.0, 123.5, 120.8, 117.3, 51.0, 46.0, 30.3, 27.6, 26.9, 21.7,
7.8.
7
,7-Dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3a)
3
Pale yellow viscous liquid; yield: 251 mg (82%).
IR (neat): 3445, 3062, 2961, 2926, 1603, 1562, 1474, 1216, 758 cm–1
.
+
ESI-MS: m/z = 298 [M + H].
1
H NMR (300 MHz, CDCl ): δ = 7.40–7.30 (m, 5 H), 6.67–6.61 (m, 1 H),
3
+
HRMS: m/z [M + H] calcd for C19H21ClN: 298.1362; found: 298.1354.
6
.37 (d, J = 7.7 Hz, 1 H), 5.69 (dt, J = 7.3, 1.3 Hz, 1 H), 4.65 (d, J = 3.2 Hz,
H), 4.29 (s, 1 H), 2.93–2.87 (m, 1 H), 2.82 (dd, J = 12.0, 6.1 Hz, 1 H),
.68–2.64 (m, 1 H), 1.83 (dt, J = 12.3, 3.4 Hz, 1 H), 1.70–1.65 (m, 1 H),
.45 (s, 3 H), 1.36 (s, 3 H).
1
2
1
9-Fluoro-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acri-
dine (3e)
1
3
Colorless viscous liquid; yield: 210 mg (75%).
IR (neat): 3420, 2925, 2854, 1615, 1470, 1275, 1187, 769 cm–1
C NMR (75 MHz, CDCl ): δ = 141.4, 130.7, 129.2, 128.2, 128.1, 127.9,
3
1
27.6, 126.7, 126.6, 124.9, 117.3, 112.6, 45.8, 40.5, 32.3, 28.3, 25.6,
.
2
5.0, 17.6.
1
H NMR (300 MHz, CDCl ): δ = 7.44 (d, J = 7.5 Hz, 1 H), 7.27–7.14 (m, 3
H), 7.00 (dd, J = 10.6, 3.0 Hz, 1 H), 6.75 (dt, J = 8.3, 2.2 Hz, 1 H), 6.61
(dd, J = 8.3, 5.3 Hz, 1 H), 4.29 (d, J = 10.6 Hz, 1 H), 4.29–4.26 (br s, 1 H),
3
+
ESI-MS: m/z = 265 [M + H].
+
HRMS: m/z [M + H] calcd for C19H22N: 264.1752; found: 264.1761.
2
.92 (dd, J = 8.3, 3.0 Hz, 2 H), 2.09–2.01 (m, 1 H), 1.77–1.65 (m, 1 H),
1
.62–1.53 (m, 1 H), 1.39 (s, 3 H), 1.23 (s, 3 H).
7
,7,9-Trimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine (3b)
13
C NMR (125 MHz, CDCl ): δ = 141.2, 139.3, 130.7, 129.8, 129.7,
Pale yellow viscous liquid; yield: 221 mg (80%).
IR (neat): 3449, 2924, 2854, 1634, 1459, 1217, 765 cm–1
3
128.2, 126.7, 126.6, 114.2, 114.0, 112.3, 112.1, 70.5, 40.9, 29.7, 28.3,
.
25.5, 25.0, 17.6.
1
H NMR (300 MHz, CDCl ): δ = 7.42 (d, J = 7.6 Hz, 1 H), 7.38–7.28 (m, 1
+
3
ESI-MS: m/z = 282 [M + H].
H), 7.20 (dt, J = 7.9, 0.6 Hz, 1 H), 7.17–7.14 (m, 1 H), 7.11 (d, J = 1.3 Hz,
1
+
HRMS: m/z [M + H] calcd for C19H21FN: 282.1658; found: 282.1668.
H), 6.85–6.83 (m, 1 H), 6.59 (d, J = 7.9 Hz, 1 H), 4.30 (d, J = 10.3 Hz, 1
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 124–128

1
27
Synthesis
G. Sabitha et al.
Paper
+
+
7,7-Dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acridin-11-ol (3f)
ESI-MS: m/z = 422 [M + 2] , 424 [M + 4] .
+
Colorless liquid; yield: 214 mg (77%).
HRMS: m/z [M + H] calcd for C19H20Br N: 419.9962; found: 419.9976.
2
IR (neat): 3422, 3066, 2966, 2928, 1617, 1452, 1216, 751 cm–1
.
1
9-Methoxy-7,7-dimethyl-5,6,6a,7,12,12a-hexahydrobenzo[c]acri-
dine-11-carboxylic Acid (3j)
H NMR (300 MHz, CDCl ): δ = 7.42–7.30 (m, 2 H), 7.28–7.19 (m, 3 H),
3
7
.19–7.12 (m, 1 H), 6.95–6.91 (m, 1 H), 6.70–6.42 (br s, 1 H), 4.81–
.46 (m, 2 H), 2.91 (dd, J = 17.0, 5.1 Hz, 1 H), 2.86–2.79 (m, 1 H), 2.32–
.99 (m, 1 H), 1.88–1.81 (m, 1 H), 1.74–1.59 (m, 1 H), 1.40 (s, 3 H),
.36 (s, 3 H).
4
1
1
Colorless gummy liquid; yield: 293 mg (87%).
IR (KBr): 3450, 2960, 1652, 1583, 1497, 1426, 1217 cm–1
.
1
H NMR (300 MHz, CDCl ): δ = 7.43 (d, J = 3.0 Hz, 1 H), 7.34–7.12 (m, 3
3
13
C NMR (75 MHz, CDCl ): δ = 137.2, 130.9, 129.3, 129.1, 129.0, 128.4,
3
H), 7.08–7.01 (m, 1 H), 6.59 (d, J = 9.0 Hz, 1 H), 4.75 (d, J = 3.0 Hz, 1 H),
1
2
27.7, 126.6, 126.5, 126.0, 116.0, 113.1, 71.4, 40.7, 29.3, 28.2, 25.5,
5.1, 17.4.
4
2
.42 (s, 1 H), 3.77 (s, 3 H), 2.92–2.77 (m, 1 H), 2.73–2.61 (m, 1 H),
.31–2.00 (m, 1 H), 1.75–1.57 (m, 2 H), 1.46 (s, 3 H), 1.34 (s, 3 H).
+
ESI-MS: m/z = 280 [M + H].
13
C NMR (75 MHz, CDCl ): δ = 173.2, 149.3, 146.9, 135.8, 129.3, 129.1,
3
+
HRMS: m/z [M + H] calcd for C19H22NO: 280.1701; found: 282.1707.
127.6, 127.2, 126.1, 124.8, 122.2, 114.4, 113.3, 55.8, 49.4, 44.9, 32.4,
1.8, 30.5, 22.5, 19.3.
3
+
7,7-Dimethyl-9-nitro-5,6,6a,7,12,12a-hexahydrobenzo[c]acridine
ESI-MS: m/z = 338 [M + H].
(3g)
+
HRMS: m/z [M + H] calcd for C21H24NO : 338.1756; found: 338.1761.
3
Yellow viscous liquid; yield: 228 mg (74%).
IR (KBr): 3402, 2953, 2865, 1603, 1510, 1318, 1279, 737 cm–1
.
8,9,10-Trimethoxy-7,7-dimethyl-5,6,6a,7,12,12a-hexahydroben-
1
zo[c]acridine (3k)
H NMR (300 MHz, CDCl ): δ = 8.12 (d, J = 2.3 Hz, 1 H), 7.91 (dt, J = 9.1,
3
2.3 Hz, 1 H), 7.33–7.23 (m, 4 H), 6.30 (d, J = 9.1 Hz, 1 H), 4.74 (d, J = 3.8
Colorless gummy liquid; yield: 282 mg (80%).
Hz, 1 H), 4.55–4.50 (br s, 1 H), 2.98–2.91 (m, 1 H), 2.89–2.84 (m, 1 H),
IR (neat): 3387, 2962, 2932, 1605, 1481, 1456, 1106, 752 cm–1
.
1.91–1.79 (m, 1 H), 1.78–1.61 (m, 1 H), 1.64–1.56 (m, 1 H), 1.53 (s, 3
1
H NMR (300 MHz, CDCl ): δ = 7.25–7.15 (m, 4 H), 5.76 (s, 1 H), 4.49
3
H), 1.35 (s, 3 H).
(d, J = 2.6 Hz, 1 H), 3.92 (s, 3 H), 3.77 (s, 3 H), 3.72 (s, 3 H), 3.59–3.53
13
C NMR (75 MHz, CDCl ): δ = 147.6, 137.6, 136.8, 136.2, 129.3, 128.8,
3
(br s, 1 H), 2.98–2.91 (m, 1 H), 2.87–2.79 (m, 1 H), 1.96–1.90 (m, 1 H),
128.3, 126.7, 126.5, 124.2, 123.0, 111.8, 50.2, 41.9, 35.4, 32.4, 29.0,
1
.73–1.64 (m, 1 H), 1.57 (m, 4 H), 1.42 (s, 3 H).
25.4, 19.2.
13
C NMR (75 MHz, CDCl ): δ = 156.7, 154.4, 152.0, 138.1, 137.2, 132.9,
3
+
ESI-MS: m/z = 309 [M + H].
129.1, 128.9 (2 C), 127.7, 125.9, 93.1, 60.6, 60.5, 55.5, 50.1, 46.1, 32.3,
+
HRMS: m/z [M + H] calcd for C19H21N O : 309.1603; found: 309.1595.
29.4, 27.1, 24.6, 19.1.
2
2
+
ESI-MS: m/z = 354 [M + H].
8
,11-Dibromo-7,7-dimethyl-5,6,6a,7,12,12a-hexahydroben-
+
HRMS: m/z [M + H] calcd for C22H28NO : 354.2069; found: 354.2058.
3
zo[c]acridine (3h)
Brown viscous liquid; yield: 359 mg (86%).
IR (neat): 3414, 3015, 2960, 2927, 1577, 1483, 1442, 1292, 742 cm–1
.
Acknowledgment
1
H NMR (300 MHz, CDCl ): δ = 7.33–7.22 (m, 3 H), 7.18 (d, J = 7.3 Hz, 1
3
K.S. thanks CSIR, New Delhi, for the award of a fellowship.
H), 7.04 (d, J = 8.4 Hz, 1 H), 6.75 (d, J = 8.4 Hz, 1 H), 4.60 (d, J = 2.7 Hz,
1
H), 4.53–4.47 (br s, 1 H), 2.95–2.90 (m, 1 H), 2.83 (dd, J = 11.7, 6.2
Hz, 1 H), 1.97–1.90 (m, 1 H), 1.80 (s, 3 H), 1.69–1.64 (m, 1 H), 1.58 (dd,
J = 12.6, 5.9 Hz, 1 H), 1.53 (s, 3 H).
Supporting Information
13
C NMR (125 MHz, CDCl ): δ = 41.5, 137.1, 136.9, 130.6, 129.2, 129.0,
Supporting information for this article is available online at
3
1
2
28.1, 127.2, 126.3, 123.6, 122.2, 107.7, 49.8, 46.8, 37.9, 29.8, 29.3,
7.4, 18.9.
http://dx.doi.org/10.1055/s-0034-1379022.
S
u
p
p
o
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+
+
ESI-MS: m/z = 422 [M + 2] , 424 [M + 4] .
References
+
HRMS: m/z [M + H] calcd for C19H20Br N: 419.9962; found: 419.9954.
2
(1) (a) Kappe, C. O.; Murphree, S. S.; Padwa, A. Tetrahedron 1997,
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zo[c]acridine (3i)
Brown viscous liquid; yield: 342 mg (82%).
IR (neat): 3412, 3015, 2961, 2927, 1577, 1443, 1293, 755 cm–1
.
1
H NMR (300 MHz, CDCl ): δ = 7.28–7.25 (m, 1 H), 7.24–7.22 (m, 2 H),
3
7.17 (d, J = 7.3 Hz, 1 H), 7.00 (d, J = 2.0 Hz, 1 H), 6.45 (d, J = 2.0 Hz, 1 H),
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(
(
1
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(2) For reviews, see: (a) Boger, D. L.; Weinreb, S. M. Hetero Diels–
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3
C NMR (125 MHz, CDCl ): δ = 145.6, 137.0, 136.2, 130.9, 129.2,
3
1
2
28.9, 128.1, 126.3, 125.4, 119.9, 115.5, 114.0, 49.3, 46.5, 37.2, 29.3,
9.6, 27.6, 19.0.
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 124–128

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Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 124–128