Simple, facile, and one-pot conversion of the Baylis-Hillman adducts into functionalized 1,2,3,4-tetrahydroacridines and cyclopenta[b]quinolines

Article abstract of DOI:10.1021/jo0489871

A simple, facile, and one-pot synthesis of functionalized 1,2,3,4-tetrahydroacridines and cyclopenta[b]-quinolines from the Baylis-Hillman alcohols, i.e., 2-[hydroxy-(2-nitroaryl)methyl]cycloalk-2-enones, is described.

Full text of DOI:10.1021/jo0489871

acrine (antiparkinasonian drug),3c,d clomacran (tran-
quilizer),3e,f monometacrine (antidepressant),3g,h and in
natural products such as plakinidine A and B3i and der-
citin.3j Also, acridine derivatives have been employed or
examined as antitumor agents,3k acetylcholinesterase in-
hibitors,3l anticancer agents,3m and DNA binding agents.3n
Cyclopenta[b]quinoline derivatives are yet another class
of important molecules which are found to possess bio-
logical properties such as antiinflammatory activity,4a
antimalarial activity,4b and cholinesterase inhibition
activity.4c Also, cyclopenta[b]quinoline moiety is present
in certain natural products such as isoschizogaline4d
and isoschizogamine.4d,e Therefore, development of simple
and convenient methodologies for synthesis of acridine
derivatives3l,m,5a-h and cyclopenta[b]quinoline deriva-
tives4b-d,5f-j is an interesting and attractive endeavor in
synthetic organic chemistry. In continuation of our inter-
est in the synthesis of heterocyclic molecules with Bay-
lis-Hillman chemistry,6 we herein report a facile and
one-pot synthesis of functionalized 1,2,3,4-tetrahydro-
acridines and cyclopenta[b]quinolines using the Baylis-
Hillman adducts.
Sim p le, F a cile, a n d On e-P ot Con ver sion of
th e Ba ylis-Hillm a n Ad d u cts in to
F u n ction a lized 1,2,3,4-Tetr a h yd r oa cr id in es
a n d Cyclop en ta [b]qu in olin es
Deevi Basavaiah,* J amjanam Srivardhana Rao, and
Raju J annapu Reddy
School of Chemistry, University of Hyderabad,
Hyderabad 500 046, India
dbsc@uohyd.ernet.in
Received J une 16, 2004
Abstr a ct: A simple, facile, and one-pot synthesis of func-
tionalized 1,2,3,4-tetrahydroacridines and cyclopenta[b]-
quinolines from the Baylis-Hillman alcohols, i.e., 2-[hydroxy-
(2-nitroaryl)methyl]cycloalk-2-enones, is described.
The Baylis-Hillman reaction is an atom-economical,
carbon-carbon, bond-forming reaction providing densely
functionalized molecules whose applications in many
organic transformation methodologies have been well
documented.1,2 Acridine moiety is an important structural
unit present in many biologically important molecules
such as amsacrine (cytotoxic, antiviral agent),3a,b boti-
Applications of the Baylis-Hillman adducts for syn-
thesis of quinolines, 1,4-dihydroquinolines, and quinoline
N-oxides have been well demonstrated.6f,7 However,
literature survey reveals that there is no report on the
synthesis of acridines and cyclopenta[b]quinolines with
the Baylis-Hillman adducts. Recently, we have reported
a simple synthesis of substituted quinolines from the
* To whom correspondence should be addressed. Fax: +91-40-
23012460.
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10.1021/jo0489871 CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/14/2004
J . Org. Chem. 2004, 69, 7379-7382
7379

SCHEME 1. Red u ctive Cycliza tion of Ba ylis-Hillm a n Alcoh ols (1a -g) w ith F e/AcOH in to
1,2,3,4-Tetr a h yd r oa cr id in es
TABLE 1. Syn th esis of F u n ction a lized 1,2,3,4-Tetr a h yd r oa cr id in es a n d Cyclop en ta [b]qu in olin esa
B-H alcohol
R1
R2
R
n
productb
yieldc (%)
mp (°C)
1a
1b
1c
1d
1e
1f
1g
1h
1i
H
H
H
H
H
H
Me
Me
Me
H
H
H
1
1
1
1
1
1
1
0
0
0
0
2d
73
76
66
78
82
62
80
79
63
61
74
71-73
98-100
58-61
OMe
OEt
H
H
OMe
H
OMe
OMe
Cl
H
OMe
Cl
3d
4d
5
79-81
6d,e
7d
62-64
112-115
124-126
8d
H
H
9
OMe
OEt
H
OMe
OMe
Cl
10d
11
12d
108-111
97-99
90-92
1j
1k
H
a
All reactions were carried out on 1 mmol scale of Baylis-Hillman alcohol with Fe powder (6 mmol)/AcOH (5 mL) at reflux (for 1a -g)
b
or 60 °C (for 1h -k ) for 2 h. 2-8 and 10-12 were obtained as solids while compound 9 was obtained as a viscous liquid. 2-12 were
characterized by IR, 1H NMR (200 MHz/400 MHz), 13C NMR (50 MHz) spectral data and elemental analysis. c Yields of pure products
d
(based on alcohols) after purification through silica gel column chromatography. Structures of these molecules were further confirmed
by mass spectral analyses. e The structure of this molecule was also established from the single-crystal X-ray data.
Baylis-Hillman adducts obtained from 2-nitrobenzal-
dehydes and acyclic enones, via the treatment with
Fe/AcOH.6f It occurred to us that the Baylis-Hillman
adducts derived from 2-nitrobenzaldehydes and cyclo-
alk-2-enones could be easily transformed into acridines
and cyclopenta[b]quinolines by treatment with Fe/AcOH
in one-pot operation. In this direction, we first carried
out the reaction of 2-[hydroxy(2-nitrophenyl)methyl]-
cyclohex-2-enone (1a ), Baylis-Hillman alcohol obtained
from 2-nitrobenzaldehyde and cyclohex-2-enone, with Fe
powder in AcOH. The best results were obtained when
Baylis-Hillman alcohol 1a was treated with Fe powder
in acetic acid at reflux for 2 h, providing the desired
product 1-acetoxy-1,2,3,4-tetrahydroacridine (2) in 73%
yield (Scheme 1).
Encouraged by this result, we have successfully trans-
formed representative Baylis-Hillman alcohols (B-H
alcohols) (1b -d ) obtained from various 2-nitrobenzal-
dehydes and cyclohex-2-enone via the treatment with
Fe/AcOH at reflux for 2 h into the desired substituted
1-acetoxy-1,2,3,4-tetrahydroacridines (3-5) in 66-78%
yields (Scheme 1, Table 1).
ment with Fe/AcOH under reflux for 2 h, in 62-82%
yields (Scheme 1, Table 1). In fact, we could obtain the
single crystals for 1-acetoxy-3,3-dimethyl-1,2,3,4-tetrahy-
droacridine (6) and further confirmed the structure of this
molecule 6 by the single-crystal X-ray data (see Support-
ing Information).
After developing a simple methodology for synthesis
of acridine derivatives, we directed our attention toward
the synthesis of cyclopenta[b]quinoline derivatives. Thus,
we have successfully employed the Baylis-Hillman al-
cohols, 2-[hydroxy(2-nitroaryl)methyl]cyclopent-2-enones
(1h -k ), obtained from cyclopent-2-enone and various
2-nitrobenzaldehydes for the synthesis of 2,3-dihydro-
1H-cyclopenta[b]quinolines (9-12) via treatment with
Fe/AcOH at 60 °C for 2 h (the reaction was not clean
at reflux temperature) in 61-79% yields (Scheme 2,
Table 1).
A plausible mechanism for the formation of tetrahy-
droacridines and cyclopenta[b]quinolines is presented
in Scheme 3. We have in fact proposed a similar mech-
anism for the formation of quinoline derivatives from
the Baylis-Hillman adducts derived via the reaction
of 2-nitrobenzaldehydes with alkyl vinyl ketones or
acrylates.6f
We have also transformed representative acetates 2
and 3 into the corresponding alcohols, 1-hydroxy-1,2,3,4-
tetrahydroacridine (13) and 6,7-dimethoxy-1-hydroxy-
We have also transformed the Baylis-Hillman alco-
hols, 5,5-dimethyl-2-[hydroxy(2-nitroaryl)methyl]cyclo-
hex-2-enones (1e-g), obtained from 5,5-dimethylcyclohex-
2-enone and various 2-nitrobenzaldehydes, into the
corresponding acridine derivatives (6-8), via the treat-
7380 J . Org. Chem., Vol. 69, No. 21, 2004

1-Acetoxy-3,3-d im eth yl-1,2,3,4-tetr a h yd r oa cr id in e (6):
yield 82%; mp 62-64 °C; IR (KBr) 1732, 1622 cm-1 1H NMR
SCHEME 2. Red u ctive Cycliza tion of
Ba ylis-Hillm a n Alch ols (1h -k ) w ith F e/AcOH in to
Cyclop en ta [b]qu in olin es
;
(200 MHz) δ 1.08 (s, 3H), 1.17 (s, 3H), 1.75-1.89 (m, 1H), 2.05-
2.27 (m, 4H), 2.92 and 3.03 (ABq, 2H, J ) 17.2 Hz), 6.25 (t, 1H,
J ) 7.4 Hz), 7.40-7.55 (m, 1H), 7.60-7.71 (m, 1H), 7.77 (d, 1H,
J ) 7.8 Hz), 8.00 (d, 1H, J ) 8.6 Hz), 8.05 (s, 1H); 13C NMR δ
21.3, 27.2, 30.3, 30.6, 41.7, 47.1, 69.5, 125.8, 126.9, 127.5, 128.0,
128.3, 129.5, 135.2, 147.5, 157.9, 170.7; EIMS (m/z) 269 (M+).
Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11; N, 5.20. Found:
C, 75.88; H, 7.17; N, 5.19. Crystal data for 6: empirical formula,
C17H19NO2; formula weight, 269.33; crystal color and habit,
colorless, rectangular; crystal dimensions, 0.6 × 0.5 × 0.4 mm3;
crystal system, triclinic; lattice type, primitive; lattice param-
eters, a ) 9.2092(9) Å, b ) 11.5236(12) Å, c ) 16.450(3) Å, R )
95.221(12)°; â ) 106.244(13)°; γ ) 113.528(9)°; V ) 1495.4(4)
1,2,3,4-tetrahydroacridine (14), by treating them respec-
tively with aqueous K2CO3/MeOH (Scheme 4).
Å3; space group, P1h (no. 2); Z ) 4; Dcalcd ) 1.196 g/cm3; F000
)
576; λ(Mo KR) ) 0.71073 Å; R (I g 2σ1) ) 0.0565, wR2 ) 0.1353.
Detailed X-ray crystallographic data are available from the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK (for compound 6 CCDC No. 238062).
1-Acet oxy-6,7-d im et h oxy-3,3-d im et h yl-1,2,3,4-t et r a h y-
d r oa cr id in e (7): yield 62%; mp 112-115 °C; IR (KBr) 1732,
1622 cm-1; 1H NMR (200 MHz) δ 1.06 (s, 3H), 1.15 (s, 3H), 1.70-
1.89 (m, 1H), 2.05-2.24 (m, 4H), 2.84 and 2.96 (ABq, 2H, J )
16.6 Hz), 3.99 (s, 3H), 4.01 (s, 3H), 6.22 (t, 1H, J ) 6.8 Hz), 7.01
(s, 1H), 7.33 (s, 1H), 7.90 (s, 1H); 13C NMR δ 21.2, 27.2, 30.1,
30.6, 41.7, 46.8, 55.76, 55.82, 69.6, 104.9, 107.0, 122.3, 125.9,
In conclusion, we have successfully developed a con-
venient, operationally simple, one-pot procedure for the
synthesis of functionalized 1,2,3,4-tetrahydroacridines
and cyclopenta[b]quinolines from Baylis-Hillman alco-
hols, thus demonstrating the application of Baylis-
Hillman chemistry in synthetic organic chemistry.
Exp er im en ta l Section :
Typ ica l Exp er im en ta l P r oced u r e. 1-Acetoxy-1,2,3,4-tet-
r a h yd r oa cr id in e (2): To a stirred solution of Baylis-Hillman
alcohol, i.e., 2-[hydroxy(2-nitrophenyl)methyl]cyclohex-2-enone
(1a ) (1 mmol, 0.247 g), in acetic acid (5 mL) was added Fe powder
(6 mmol, 0.335 g) and the reaction mixture was heated under
reflux for 2 h. Then the reaction mixture was cooled to room
temperature and acetic acid was removed under reduced pres-
sure. The reaction mixture was diluted with EtOAc (10 mL) and
stirred for 2 min and filtered to remove any iron impurities. The
insoluble iron residue was washed with EtOAc (10 mL). The
filtrate and washings were combined and dried over anhydrous
Na2SO4. Solvent (EtOAc) was removed under reduced pressure
and the crude product thus obtained was purified by column
chromatography (silica gel, 10% EtOAc in hexanes) to afford the
desired 1-acetoxy-1,2,3,4-tetrahydroacridine 2 as a light yellow
solid in 73% (0.176 g) yield; mp 71-73 °C; IR (KBr) 1726, 1620
133.5, 144.7, 149.4, 152.7, 155.2, 170.7; LCMS (m/z) 330 (M+
1). Anal. Calcd for C19H23NO4: C, 69.28; H, 7.04; N, 4.25.
Found: C, 69.16; H, 7.00; N, 4.29.
+
1-Acetoxy-7-ch lor o-3,3-d im eth yl-1,2,3,4-tetr a h yd r oa cr i-
d in e (8): yield 80%; mp 124-126 °C; IR (KBr) 1726, 1614 cm-1
;
1H NMR (200 MHz) δ 1.07 (s, 3H), 1.16 (s, 3H), 1.71-1.90 (m,
1H), 2.06-2.31 (m, 4H), 2.88 and 2.99 (ABq, 2H, J ) 18.6 Hz),
6.22 (t, 1H, J ) 6.8 Hz), 7.59 (dd, 1H, J ) 1.8 and 8.8 Hz), 7.76
(d, 1H, J ) 1.8 Hz), 7.92 (d, 1H, J ) 8.8 Hz), 7.96 (s, 1H); 13C
NMR δ 21.3, 27.3, 30.4, 30.7, 41.7, 47.1, 69.3, 126.2, 127.5, 129.2,
130.1, 130.5, 131.5, 134.2, 145.9, 158.4, 170.7; EIMS (m/z) 303
(M+), 305 (M+ + 2). Anal. Calcd for C17H18NO2Cl: C, 67.21; H,
5.97; N, 4.61. Found: C, 67.49; H, 6.00; N, 4.58.
1-Acetoxy-2,3-dih ydr o-1H-cyclopen ta[b]qu in olin e (9): To
a stirred solution of Baylis-Hillman alcohol, 2-[hydroxy(2-
nitrophenyl)methyl]cyclopent-2-enone (1h ) (1 mmol, 0.233 g), in
acetic acid (5 mL) was added Fe powder (6 mmol, 0.335 g) and
the reaction mixture was heated at 60 °C for 2 h. Then the
reaction mixture was worked up following the similar procedure
as mentioned for 2 and the product thus obtained was purified
by column chromatography (silica gel, 8% EtOAc in hexanes) to
afford 1-acetoxy-2,3-dihydro-1H-cyclopenta[b]quinoline (9) as a
viscous colorless liquid in 79% yield (0.179 g). IR (neat) 1736,
1
cm-1; H NMR (400 MHz) δ 1.98-2.31 (m, 7H), 3.07-3.32 (m,
2H), 6.23 (t, 1H, J ) 5.2 Hz), 7.48-7.54 (m, 1H), 7.68-7.75 (m,
1H), 7.80 (d, 1H, J ) 7.6 Hz), 8.02 (d, 1H, J ) 8.8 Hz), 8.14 (s,
1H); 13C NMR δ 18.6, 21.3, 28.8, 32.9, 69.8, 125.8, 126.8, 127.7,
128.3, 128.8, 129.7, 136.6, 147.6, 158.5, 170.5; EIMS (m/z) 241
(M+). Anal. Calcd for C15H15NO2: C, 74.67; H, 6.27; N, 5.80.
Found: C, 74.87; H, 6.26; N, 5.75.
1-Ace t oxy-6,7-d im e t h oxy-1,2,3,4-t e t r a h yd r oa cr id in e
1626 cm-1 1H NMR (400 MHz) δ 2.11 (s, 3H), 2.25-2.36 (m,
;
(3): yield 76%; mp 98-100 °C; IR (KBr) 1730, 1620 cm-1 1H
;
1H), 2.56-2.68 (m, 1H), 3.11-3.21 (m, 1H), 3.35-3.46 (m, 1H),
6.31-6.37 (m, 1H), 7.50-7.57 (m, 1H), 7.69-7.76 (m, 1H),
7.84 (dd, 1H, J ) 1.2 and 8.4 Hz), 8.07 (d, 1H, J ) 8.4 Hz), 8.22
(s, 1H); 13C NMR δ 21.0, 30.5, 32.0, 75.5, 125.8, 127.0, 128.2,
128.6, 129.6, 132.8, 133.4, 148.8, 166.0, 170.8. Anal. Calcd for
C14H13NO2: C, 73.99; H, 5.77; N, 6.16. Found: C, 73.77; H, 5.82;
N, 6.09.
NMR (200 MHz) δ 1.88-2.29 (m, 7H), 2.91-3.30 (m, 2H), 3.99
(s, 3H), 4.01 (s, 3H), 6.17 (t, 1H, J ) 4.8 Hz), 7.01 (s, 1H), 7.34
(s, 1H), 7.97 (s, 1H); 13C NMR δ 18.6, 21.4, 28.9, 32.5, 55.9, 56.1,
70.0, 105.0, 106.8, 122.4, 126.8, 135.4, 144.7, 149.4, 153.0, 155.9,
170.7; LCMS (m/z) 302 (M+ + 1). Anal. Calcd for C17H19NO4:
C, 67.76; H, 6.36; N, 4.65. Found: C, 67.87; H, 6.35; N, 4.67.
1-Acet oxy-6-et h oxy-7-m et h oxy-1,2,3,4-t et r a h yd r oa cr i-
d in e (4): yield 66%; mp 58-61 °C; IR (KBr) 1707, 1622 cm-1
;
1-Acetoxy-2,3-d ih yd r o-6,7-d im eth oxy-1H-cyclop en ta [b]-
qu in olin e (10): Yield 63%; mp 108-111 °C; IR (KBr) 1728,
1H NMR (200 MHz) δ 1.55 (t, 3H, J ) 7.4 Hz), 1.90-2.29 (m,
7H), 2.90-3.28 (m, 2H), 3.98 (s, 3H), 4.25 (q, 2H, J ) 7.4 Hz),
6.17 (t, 1H, J ) 4.8 Hz), 7.00 (s, 1H), 7.31 (s, 1H), 7.95 (s, 1H);
13C NMR δ 14.5, 18.8, 21.5, 29.0, 32.7, 56.0, 64.4, 70.1, 105.2,
107.8, 122.3, 126.8, 135.2, 145.0, 149.7, 152.3, 156.0, 170.8; EIMS
(m/z) 315 (M+). Anal. Calcd for C18H21NO4: C, 68.55; H, 6.71;
N, 4.44. Found: C, 68.39; H, 6.78; N, 4.41.
1620 cm-1 1H NMR (200 MHz) δ 2.07 (s, 3H), 2.17-2.35
;
(m, 1H), 2.47-2.69 (m, 1H), 2.97-3.16 (m, 1H), 3.25-3.44 (m,
1H), 3.99 (s, 3H), 4.02 (s, 3H), 6.28 (dd, 1H, J ) 3.6 and 7.0 Hz),
7.05 (s, 1H), 7.39 (s, 1H), 8.04 (s, 1H); 13C NMR δ 21.0, 30.4,
31.8, 55.8, 55.9, 76.0, 105.8, 107.4, 122.3, 130.9, 131.8, 145.9,
149.1, 152.6, 163.6, 170.8; EIMS (m/z) 287 (M+). Anal. Calcd for
C
16H17NO4: C, 66.89; H, 5.96; N, 4.87. Found: C, 67.08; H, 5.94;
N, 4.91.
1-Acetoxy-2,3-dih ydr o-6-eth oxy-7-m eth oxy-1H-cyclopen t-
1-Acetoxy-7-ch lor o-1,2,3,4-tetr a h yd r oa cr id in e (5): yield
78%; mp 79-81 °C; IR (KBr) 1734, 1620 cm-1 1H NMR (400
;
MHz) δ 1.94-2.27 (m, 7H), 2.99-3.11 (m, 1H), 3.15-3.25 (m,
1H), 6.15 (t, 1H, J ) 4.0 Hz), 7.57 (dd, 1H, J ) 2.0 and 8.8 Hz),
7.71 (d, 1H, J ) 2.0 Hz), 7.90 (d, 1H, J ) 8.8 Hz), 8.00 (s, 1H);
13C NMR δ 18.6, 21.4, 28.8, 32.9, 69.8, 126.3, 127.5, 130.0, 130.8,
131.6, 135.7, 146.0, 159.0, 170.6. Anal. Calcd for C15H14NO2Cl:
C, 65.34; H, 5.12; N, 5.08. Found: C, 65.40; H, 5.09; N, 5.10.
a [b]qu in olin e (11): yield 61%; mp 97-99 °C; IR (KBr) 1730,
1
1620 cm-1; H NMR (200 MHz) δ 1.55 (t, 3H, J ) 6.8 Hz), 2.08
(s, 3H), 2.16-2.36 (m, 1H), 2.49-2.70 (m, 1H), 2.99-3.20 (m,
1H), 3.24-3.47 (m, 1H), 3.99 (s, 3H), 4.26 (q, 2H, J ) 6.8 Hz),
6.28 (dd, 1H, J ) 3.8 and 6.8 Hz), 7.05 (s, 1H), 7.37 (s, 1H), 8.05
J . Org. Chem, Vol. 69, No. 21, 2004 7381

SCHEME 3. Red u ctive Cycliza tion of Ba ylis-Hillm a n Alcoh ols w ith F e/AcOH: Mech a n ism
7.56 (m, 1H), 7.61-7.74 (m, 1H), 7.78 (dd, 1H, J ) 1.2 and 8.0
SCHEME 4. Hyd r olysis of Aceta tes in to Alcoh ols
w ith Aqu eou s K2CO3/MeOH
Hz), 7.99 (d, 1H, J ) 8.6 Hz), 8.25 (s, 1H); 13C NMR δ 19.0, 32.5,
33.1, 68.6, 125.9, 127.3, 127.7, 128.3, 129.5, 133.4, 135.4, 147.4,
158.5; LCMS (m/z) 200 (M+ + 1). Anal. Calcd for C13H13NO: C,
78.36; H, 6.58; N, 7.03. Found: C, 78.49; H, 6.55; N, 7.10.
6,7-Dim e t h oxy-1-h yd r oxy-1,2,3,4-t e t r a h yd r oa cr id in e
(14): yield 72%; mp 133-136 °C; IR (KBr) 3119 cm-1; 1H NMR
(200 MHz) δ 1.80-2.45 (m, 5H), 2.90-3.20 (m, 2H), 3.97 (s, 3H),
3.98 (s, 3H), 4.90-5.01 (m, 1H), 6.94 (s, 1H), 7.30 (s, 1H), 8.05
(s, 1H); 13C NMR δ 19.0, 32.6, 32.8, 56.0, 56.1, 68.5, 105.0, 107.0,
122.7, 131.3, 134.0, 144.5, 149.4, 152.7, 155.8. Anal. Calcd for
(s, 1H); 13C NMR δ 14.5, 21.2, 30.6, 31.9, 55.9, 64.3, 76.1, 105.9,
108.1, 122.3, 131.0, 132.0, 146.0, 149.5, 152.0, 163.7, 171.1. Anal.
Calcd for C17H19NO4: C, 67.76; H, 6.36; N, 4.65. Found: C, 67.51;
H, 6.40; N, 4.63.
C
15H17NO3: C, 69.48; H, 6.61; N, 5.40. Found: C, 69.26; H, 6.64;
N, 5.36.
Ack n ow led gm en t. We thank CSIR (New Delhi) for
1-Acetoxy-7-ch lor o-2,3-d ih yd r o-1H-cyclop en ta [b]qu in o-
funding this project. We thank UGC (New Delhi) for
recognizing our University of Hyderabad as “University
with potential for excellence” (UP E) and also recogniz-
ing our School of Chemistry as a Center for Advanced
Studies in Chemistry and providing some instrumental
facilities. J .S.R. thanks UGC and DST (New Delhi) and
R.J .R. thanks CSIR (New Delhi) for their research
fellowships. We also thank the National Single Crystal
X-ray Facility in our School of Chemistry funded by the
DST (New Delhi). We thank Prof. T. P. Radhakrishnan
for helpful discussions regarding the X-ray crystal
structure.
lin e (12): yield 74%; mp 90-92 °C; IR (KBr) 1724, 1622 cm-1
;
1H NMR (200 MHz) δ 2.09 (s, 3H), 2.18-2.38 (m, 1H), 2.52-
2.73 (m, 1H), 3.05-3.21 (m, 1H), 3.28-3.48 (m, 1H), 6.29 (dd,
1H, J ) 4.0 and 6.8 Hz), 7.63 (dd, 1H, J ) 2.0 and 8.8 Hz), 7.79
(d, 1H, J ) 2.0 Hz), 7.98 (d, 1H, J ) 8.8 Hz), 8.10 (s, 1H); 13C
NMR δ 21.0, 30.6, 32.0, 75.4, 126.9, 127.8, 130.3, 130.5, 131.6,
132.4, 134.0, 147.4, 166.6, 170.8; EIMS (m/z) 261 (M+), 263 (M+
+ 2). Anal. Calcd for C14H12NO2Cl: C, 64.25; H, 4.62; N, 5.35.
Found: C, 64.35; H, 4.67; N, 5.40.
1-Hyd r oxy-1,2,3,4-tetr a h yd r oa cr id in e (13): A mixture of
1-acetoxy-1,2,3,4-tetrahydroacridine (2) (0.5 mmol, 0.120 g) and
K2CO3 (1.5 mmol, 0.207 g) in methanol (2 mL) containing a drop
of water was stirred at room temperature for 1 h. The salts were
removed by filtration and washed with methanol (2 × 5 mL).
The filtrate and washings were combined. Solvent was removed
and the crude product thus obtained was subjected to crystal-
lization from methanol at 0 °C to provide 1-hydroxy-1,2,3,4-
tetrahydroacridine (13) as a colorless solid in 80% (0.079 g) yield;
Su p p or tin g In for m a tion Ava ila ble: ORTEP diagram for
compound 6, general experimental details, and 13C NMR
spectra of all products 2-14; crystallographic information data
file for 6 (CIF). This material is available free of charge via
the Internet at http://pubs.acs.org.
mp 161-163 °C; IR (KBr) 3196 cm-1
;
1H NMR (200 MHz) δ
1.84-2.33 (m, 5H), 3.05-3.23 (m, 2H), 4.95-5.10 (m, 1H), 7.41-
J O0489871
7382 J . Org. Chem., Vol. 69, No. 21, 2004