Three-component one-pot synthesis of polyhydroacrodine derivatives in aqueous media

Article abstract of DOI:10.1080/00397910802431057

9,10-Diaryldecahydroacridine-1,8-diones were synthesized by a three-component reaction of aromatic aldehydes, aromatic amines, and 5,5-dimethyl-1,3-cyclohexanedione using sodium 1-dodecanesulfonic (SDS) as the catalyst in aqueous media. The key intermedia

Full text of DOI:10.1080/00397910802431057

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Three-Component One-Pot
Synthesis of Polyhydroacrodine
Derivatives in Aqueous Media
Da-Qing Shi a b , Jing-Wen Shi b & Hao Yao b
a College of Chemistry and Chemical Engineering,
Key Laboratory of Organic Synthesis of Jiangsu
Province, Suzhou University , Suzhou, China
b College of Chemistry and Chemical Engineering,
Xuzhou Normal University , Xuzhou, China
Published online: 28 Jan 2009.
To cite this article: Da-Qing Shi , Jing-Wen Shi & Hao Yao (2009) Three-Component
One-Pot Synthesis of Polyhydroacrodine Derivatives in Aqueous Media, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:4, 664-675, DOI: 10.1080/00397910802431057
To link to this article: http://dx.doi.org/10.1080/00397910802431057
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Synthetic Communications1, 39: 664–675, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802431057
Three-Component One-Pot Synthesis of
Polyhydroacrodine Derivatives in Aqueous Media
Da-Qing Shi,1,2 Jing-Wen Shi,2 and Hao Yao2
1College of Chemistry and Chemical Engineering, Key Laboratory of
Organic Synthesis of Jiangsu Province, Suzhou University, Suzhou, China
2College of Chemistry and Chemical Engineering, Xuzhou Normal
University, Xuzhou, China
Abstract: 9,10-Diaryldecahydroacridine-1,8-diones were synthesized by a three-
component reaction of aromatic aldehydes, aromatic amines, and 5,5-dimethyl-
1,3-cyclohexanedione using sodium 1-dodecanesulfonic (SDS) as the catalyst in
aqueous media. The key intermediates before the cyclization step were obtained
and characterized. The structures of all the products were determined by
IR and 1H NMR spectra and further confirmed by single-crystal x-ray diffraction
analysis.
Keywords: Aqueous media, one-pot synthesis, polyhydroacridine, three-
component reaction
1,4-Dihydropyridines (1,4-DHPs) are well-known compounds because of
their biological activities.[1,2] Recently there have been many methods
reported for the synthesis of tricyclic compounds containing 1,4-dihydro-
pyridines, such as acridine derivatives, from aldehydes and dimedone
and aromatic amines by traditional heating in organic solvent,[3] in pure
water,[4] in water catalyzed by 4-dodecylbenzenesulfonic acid (DBSA),[5]
or under microwave irradiation.[6] However, these methods usually require
forcing conditions or use of organic solvents, and none of the acridine com-
pounds containing N-aryl substituted with electron-withdrawing groups at
Received March 11, 2008.
Address correspondence to Da-Qing Shi, College of Chemistry and Chemical
Engineering, Suzhou Normal University, Suzhou 221116, China. E-mail: dqshi@
suda.edu.cn
664

Synthesis of Polyhydroacrodine Derivatives
665
the para-position were obtained. Thus new routes for the synthesis of these
molecules have attracted considerable attention in the search for a rapid
entry to these heterocycles.
Multicomponent reactions (MCRs), in which multiple reactions are
combined into one synthetic operation, have been used extensively to
form carbon–carbon bonds in synthetic chemistry.[7] Such reactions offer
a wide range of possibilities for the efficient construction of highly com-
plex molecules in a single procedural step, avoid the complicated purifica-
tion operations, and allow savings of both solvents and reagents. In the
past decade, there have been tremendous development in three- and
four-component reactions, and great efforts continue to be made to
develop new MCRs.[8–15] The need to reduce the amount of toxic waste
and by-products arising from chemical processes requires increasing
emphasis on the use of less toxic and environmentally compatible materi-
als in the design of new synthetic methods. One of most promising
approaches is using water as the reaction media. Breslow,[16] who showed
that hydrophobic effects could strongly enhance the rate of several
organic reactions, rediscovered the use of water as a solvent in organic
chemistry in the 1980s. There has been growing recognition that water
is an attractive medium for many organic reactions,[17] and many MCRs
in aqueous medium have been reported.[18] As part of our current studies
on the developments of new routes to a heterocyclic system,[19] we now
report an efficient and clean synthetic route to polyhydro-acridine
derivatives in aqueous media.
When aromatic aldehyde 1, 5,5-dimethyl-1,3-cyclohexanedione 2,
and aromatic amine 3 were treated in water in the presence of SDS
at 90 ꢀC for 6–20 h, the desired 3,3,6,6-tetramethyl-9,10-diaryl-1,2,3,4,
5,6,7,8,9,10-decalydroacridin-1,8-dione derivatives 4, accomplished with
an intermediate 3-hydrox-30-arylaminoarylmethylenebis(5,5-dimethyl-2-
cyclo-hexene-1-one-2-yl) 5, were obtained (Scheme 1). The results are
summarized in Table 1.
As shown in Table 1, this method could be applied not only to aro-
matic aldehydes with electron-withdrawing groups (such as halide
groups) but also to aromatic aldehydes with electron-donating groups
(such as alkoxyl and hydroxyl groups). Furthermore, it was particularly
Scheme 1. The synthesis of polyhydroacrodine in aqueous media.

666
D.-Q. Shi, J.-W. Shi, and H. Yao
Table 1. Synthesis of 4 and 5 in aqueous media in the presence of SDS
Isolated yield (%)
Reaction
Entry
Ar1
Ar2
time (h)
4
5
a
b
c
d
e
f
3,4-OCH2OC6H3
4-BrC6H4
4-ClC6H4
4-HOC6H4
3,4-OCH2OC6H3
4-ClC6H4
4-CH3OC6H4
4-CH3OC6H4
C6H5
C6H5
C6H5
4-FC6H4
4-ClC6H4
20
16
10
9
15
6
68
56
72
70
68
67
67
17
11
Trace
Trace
12
Trace
17
g
4-BrC6H4
8
noteworthy that the method could be applied to aromatic amine with
either electron-donating groups (such as alkoxyl group) or electron-
withdrawing groups (such as halide groups), which highlighted the wide
scope of this three-component reaction.
The structures of products 4 and 5 were identified by their spectro-
scopy analysis. The structures of 4a and 5a were further confirmed by
x-ray diffraction analysis. The molecular structures of 4a and 5a are
shown in Figs. 1 and 2, respectively.
Though the detailed mechanism of this reaction has not been fully
clarified yet, the formation of 4 and 5 can be explained by the possible
mechanism presented in Scheme 2. The reaction occurs via an initial
formation of the imine from the condensation of aldehyde and amine,
which suffer nucleophilic attack by 5,5-dimethyl-1,3-cyclohexanedione
and loses the amine to give the intermediate A. Condensation of another
5,5-dimethyl-1,3-cyclohexanedione and amine take place and give
another intermediate enamines B. Then, the Michael additation, cycliza-
tion, and dehydration between intermediates A and B take place and give
intermediate 5 and products 4.
Evidence supporting this proposed mechanism came from the obser-
vation that when intermediate imine and 2 were treated under same reac-
tion conditions, the expected 4 and 5 were obtained in a yield similar to
that obtained in the one-pot reaction.
In conclusion, a series of 3,3,6,6-tetramethyl-9,10-diaryl-1,2,3,4,5,
6,7,8,9,10-decahydroacridine-1,8-diones were synthesized by a three-
component reaction of aromatic aldehydes, 5,5-dimethyl-1,3-cyclohexa-
nedione, and aromatic amines in aqueous media. The advantages of this
method are easier workup, milder reaction conditions, environmentally
benign procedure, and wide scope.

Synthesis of Polyhydroacrodine Derivatives
667
Figure 1. ORTEP diagram of 4a.
Figure 2. ORTEP diagram of 5a.

668
D.-Q. Shi, J.-W. Shi, and H. Yao
Scheme 2. A proposed mechanism for the synthesis of polyhydroacridine.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
IR spectra were recorded on a Tensor 27 spectrameter in KBr with
absorptions in cmÀ1. 1H NMR and 13C NMR were measured on a Bruker
DPX 400-MHz spectrometer in DMSO-d6 with TMS as internal standard.
Microanalyses were carried out on Perkin-Elmer 2400 II instruments.
X-ray diffraction was recorded on a Smart-1000 diffractometer.
General Procedure for the Three-Component Reaction of Aldehydes, 5,5-
Dimethyl-1,3-Cyclohexanedione, and Aromatic Amines in Aqueous Media
A mixture of an aromatic aldehyde 1 (2 mmol), 5,5-dimethyl-1,3-cyclo-
hexanedione 2 (4 mmol), aromatic amine 3 (2 mmol), and SDS (0.2 g)

Synthesis of Polyhydroacrodine Derivatives
669
in water (10 mL) was stirred for 6–20 h at 90 ꢀC, and then the reaction
mixture was cooled to room temperature. The crystalline powder formed
was collected by filtration, washed with water, and purified by column
chromatography on silica gel (200–300 mesh) using petroleum ether
(60–90 ꢀC)–acetone (5:1) as an eluent to give 4 and 5, respectively.
Spectral Data
3,3,6,6-Tetramethyl-9-(3,4-methylenedioxylphenyl)-10-(4-methoxyphe-
nyl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4a)
Mp 227–229 ꢀC (lit.[22] mp 227–229 ꢀC); 1H NMR (DMSO-d6) d: 0.74 (6H,
s, 2 ꢁ CH3), 0.89 (6H, s, 2 ꢁ CH3), 1.80 (2H, d, J ¼ 17.6 Hz, 2 ꢁ CH), 2.02
(2H, d, J ¼ 16.0 Hz, 2 ꢁ CH), 2.18 (2H, d, J ¼ 16.0 Hz, 2 ꢁ CH), 2.19 (2H,
d, J ¼ 17.6 Hz, 2 ꢁ CH), 3.85 (3H, s, CH3O), 4.95 (1H, s, CH), 5.94 (2H, s,
OCH2O), 6.74–6.80 (3H, m, ArH), 7.11–7.21 (3H, m, ArH), 7.37 (1H, s,
ArH); IR (KBr) n: 1639, 1574, 1510, 1486, 1440, 1361, 1295, 1247, 1222,
1141, 1042, 943, 851, 805 cmꢂ1. Anal. calcd. for C31H33NO5: C, 74.53,
H, 6.66; N, 2.80; found: C, 74.68; H, 6.62; N, 2.85.
3-Hydroxy-30-(4-methoxyphenylamino)(3,4-methylenedioxyphenyl-
menthylene)bis(5,5-dimethyl-2-cyclohexene-1-one-2-yl) (5a)
1
Mp 160–162 ꢀC; H NMR (DMSO-d6) d: 0.92 (3H, s, CH3), 1.04 (6H, s,
2 ꢁ CH3), 1.10 (3H, s, CH3), 2.14 (1H, d, J ¼ 16.4 Hz, CH), 2.26–2.46
(6H, m, 6 ꢁ CH), 2.63 (1H, d, J ¼ 17.6 Hz, CH), 3.78 (3H, s, CH3O),
5.51 (1H, s, CH), 5.96 (2H, s, OCH2O), 6.58 (1H, d, J ¼ 8.0 Hz, ArH),
6.62 (1H, s, ArH), 6.79 (1H, d, J ¼ 8.0 Hz, ArH), 6.99 (2H, d, J ¼ 8.4 Hz,
ArH), 7.11 (2H, d, J ¼ 8.0 Hz, ArH), 9.88 (1H, s, NH), 13.27 (1H, s, OH);
13C NMR (DMSO-d6) d: 27.49, 27.65, 27.80, 28.14, 31.36, 32.03, 32.77,
43.73, 49.00, 55.34, 100.65, 103.34, 107.38, 107.48, 107.59, 114.58,
114.80, 119.22, 126.42, 130.79, 144.69, 147.16, 147.20, 157.50, 195.48;
IR (KBr) n: 3263, 3061, 1639, 1579, 1514, 1485, 1394, 1293, 1257, 1226,
1177, 1116, 1092, 1036, 938, 859, 835, 816, 742 cmꢂ1. Anal. calcd. for
C31H35NO6: C, 71.93; H, 6.82; N, 2.71; found: C, 72.06; H, 6.89; N, 2.64.
3,3,6,6-Tetramethyl-9-(4-bromophenyl)-10-(4-methoxyphenyl)-
1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4b)
1
Mp 254–256 ꢀC (lit.[22] mp 247–248 ꢀC); H NMR (DMSO-d6) d: 0.72
(6H, s, 2 ꢁ CH3), 0.88 (6H, s, 2 ꢁ CH3), 1.80 (2H, d, J ¼ 17.6 Hz,

670
D.-Q. Shi, J.-W. Shi, and H. Yao
2 ꢁ CH), 1.94 (2H, d, J ¼ 16.0 Hz, 2 ꢁ CH), 2.18 (2H, d, J ¼ 16.0 Hz,
2 ꢁ CH), 2.20 (2H, d, J ¼ 17.6 Hz, 2 ꢁ CH), 3.86 (3H, s, CH3O), 5.00 (1H,
s, CH), 7.13 (2H, d, J ¼ 8.8 Hz, ArH), 7.26 (2H, d, J ¼ 8.4 Hz, ArH),
7.30–7.39 (2H, m, ArH), 7.44 (2H, d, J ¼ 8.4 Hz, ArH); IR (KBr) n:
1637, 1572, 1512, 1484, 1424, 1405, 1360, 1295, 1250, 1174, 1143, 1121,
1068, 1032, 1010, 885, 847, 775, 746 cmꢂ1. Anal. calcd. for C30H32BrNO3:
C, 67.41; H, 6.03; N, 2.62; found: C, 67.38; H, 6.12; N 2.65.
3-Hydroxy-30-(4-methoxyphenylamino)(4-bromophenylmenthylene)-
bis(5,5-dimethyl-2-cyclohexene-1-one-2-yl) (5b)
1
Mp 176–178 ꢀC; H NMR (DMSO-d6) d: 0.92 (3H, s, CH3), 1.04 (6H, s,
2 ꢁ CH3), 1.10 (3H, s, CH3), 2.16 (1H, d, J ¼ 17.2 Hz, CH), 2.25–2.45
(7H, m, 7 ꢁ CH), 3.77 (3H, s, CH3O), 5.55 (1H, s, CH), 6.99 (2H, d,
J ¼ 8.4 Hz, ArH), 7.05 (2H, d, J ¼ 8.4 Hz, ArH), 7.11 (2H, d, J ¼ 8.4 Hz,
ArH), 9.88 (1H, s, NH), 13.17 (1H, s, OH); 13C NMR (DMSO-d6) d:
27.60, 29.28, 31.38, 31.91, 32.07, 32.72, 40.95, 48.93, 49.49, 55.33,
112.50, 114.59, 118.03, 118.70, 126.42, 129.01, 129.84, 130.64, 130.70,
130.78, 130.82, 151.08, 195.43, 195.46; IR (KBr) n: 3250, 1587, 1511,
1458, 1397, 1297, 1276, 1246, 1167, 1123, 1106, 1070, 1037, 1005, 946,
919, 890, 829, 751 cmꢂ1. Anal. calcd. for C30H34BrNO4: C, 65.22, H,
6.20, N, 2.54; found: C, 65.32; H, 6.12; N, 2.58.
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-10-phenyl-1,2,3,4,5,6,7,8,9,10-
decahydroacridine-1,8-dione (4c)
1
Mp 233–235 ꢀC (lit.[22] mp 231–233 ꢀC); H NMR (DMSO-d6) d: 0.71
(6H, s, 2 ꢁ CH3), 0.90 (6H, s, 2 ꢁ CH3), 1.99 (2H, d, J ¼ 17.2 Hz,
2 ꢁ CH), 2.01 (2H, d, J ¼ 16.0 Hz, 2 ꢁ CH), 2.18 (2H, d, J ¼ 16.0 Hz,
2 ꢁ CH), 2.23 (2H, d, J ¼ 17.2 Hz, 2 ꢁ CH), 5.03 (1H, s, CH), 7.30–7.34
(4H, m, ArH), 7.39–7.48 (2H, m, ArH), 7.57–7.64 (3H, m, ArH); IR
(KBr) n: 1634, 1592, 1575, 1489, 1453, 1274, 1260, 1224, 1176, 1141,
1122, 1000, 888, 839, 705 cmꢂ1. Anal. calcd. for C29H30ClNO2: C,
75.72; H, 6.57; N, 3.04; found: C, 75.81; H, 6.49; N, 2.95.
3,3,6,6-Tetramethyl-9-(4-hydroxyphenyl)-10-phenyl-
1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4d)
Mp 250–252 ꢀC; 1H NMR (DMSO-d6) d: 0.71 (6H, s, 2 ꢁ CH3), 0.87 (6H,
s, 2 ꢁ CH3), 1.73 (2H, d, J ¼ 17.6 Hz, 2 ꢁ CH), 2.00 (2H, d, J ¼ 16.0 Hz,
2 ꢁ CH), 2.16–2.21 (4H, m, 4 ꢁ CH), 4.94 (1H, s, CH), 6.62 (2H, d,

Synthesis of Polyhydroacrodine Derivatives
671
J ¼ 8.0 Hz, ArH), 7.09 (2H, d, J ¼ 8.0 Hz, ArH), 7.32–7.61 (5H, m, ArH),
9.12 (1H, s, OH); 13C NMR (DMSO-d6) d: 26.09, 29.34, 31.95, 40.96,
49.63, 113.37, 114.65, 128.37, 128.54, 129.35, 130.46, 137.00, 138.55,
149.88, 155.27, 195.10; IR (KBr) n: 3169, 3054, 1654, 1635, 1610, 1592,
1565, 1509, 1490, 1450, 1389, 1369, 1315, 1255, 1169, 1143, 1121, 835,
699 cmꢂ1. Anal. calcd. for C29H31NO3: C, 78.88; H, 7.08; N, 3.17; found:
C, 78.97; H, 7.15; N, 3.12.
3,3,6,6-Tetramethyl-9-(3,4-methylenedioxylphenyl)-10-phenyl-
1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4e)
Mp > 300 ꢀC; 1H NMR (DMSO-d6) d: 0.74 (6H, s, 2 ꢁ CH3), 0.88 (6H, s,
2 ꢁ CH3), 1.74 (2H, d, J ¼ 17.6 Hz, 2 ꢁ CH), 2.00 (2H, d, J ¼ 16.0 Hz,
2 ꢁ CH), 2.17–2.22 (4H, m, 4 ꢁ CH), 4.97 (1H, s, CH), 5.94 (2H, s,
OCH2O), 7.38–7.39 (2H, m, ArH), 7.57–7.64 (3H, m, ArH), 7.79–7.81
(3H, m, ArH); 13C NMR (DMSO-d6) d: 26.18, 29.26, 31.60, 31.97,
40.96, 49.56, 100.59, 107.83, 108.21, 113.02, 120.28, 129.40, 138.41,
140.54, 145.14, 145.92, 146.70, 150.14, 195.13; IR (KBr) n: 3055, 1638,
1592, 1577, 1489, 1441, 1361, 1296, 1278, 1253, 1178, 1038, 939, 923,
863, 800, 706 cmꢂ1. Anal. calcd. for C30H31NO4: C, 76.73; H, 6.65; N,
2.98; found: C, 76.95; H, 6.58; N, 3.06.
3-Hydroxy-30-(phenylamino)(3,4-methylenedioxyphenylmenthylene)-
bis(5,5-dimethyl-2-cyclohexene-1-one-2-yl) (5e)
1
Mp 170–172 ꢀC; H NMR (DMSO-d6) d: 0.92 (3H, s, CH3), 1.05 (6H, s,
2 ꢁ CH3), 1.10 (3H, s, CH3), 2.32 (1H, d, J ¼ 16.0 Hz, CH), 2.36–2.40
(4H, m, 4 ꢁ CH), 2.51–2.54 (3H, m, 3 ꢁ CH), 5.54 (1H, s, CH), 5.95
(2H, s, OCH2O), 6.29–6.59 (4H, m, ArH), 7.17–7.45 (4H, m, ArH),
10.05 (1H, s, NH), 12.97 (1H, s, OH); 13C NMR (DMSO-d6) d: 27.23,
27.48, 27.98, 28.08, 31.38, 32.43, 32.84, 43.68, 49.22, 49.65, 100.66,
107.32, 107.59, 109.32, 111.39, 113.84, 119.22, 124.31, 125.67, 129.40,
133.91, 138.29, 144.73, 147.20, 196.30, 199.07; IR (KBr) n: 3265, 1583,
1535, 1499, 1487, 1435, 1395, 1327, 1311, 1275, 1232, 1156, 1126, 1062,
1038, 935, 892, 815, 797, 765, 698 cmꢂ1. Anal. calcd. for C30H33NO5:
C, 73.90; H, 6.82; N, 2.87; found: C, 74.08; H, 6.72; N, 2.81.
3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-10-(4-fluorophenyl)-
1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4f)
1
Mp 285–287 ꢀC (lit.[22] mp 296–298 ꢀC); H NMR (DMSO-d6) d: 0.72
(6H, s, 2 ꢁ CH3), 0.89 (6H, s, 2 ꢁ CH3), 1.77 (2H, d, J ¼ 17.2 Hz,

672
D.-Q. Shi, J.-W. Shi, and H. Yao
2 ꢁ CH), 2.01 (2H, d, J ¼ 16.0 Hz, 2 ꢁ CH), 2.19 (2H, d, J ¼ 16.0 Hz,
2 ꢁ CH), 2.21 (2H, d, J ¼ 17.2 Hz, 2 ꢁ CH), 5.01 (1H, s, CH), 7.28–7.34
(4H, m, ArH), 7.43–7.49 (4H, m, ArH); IR (KBr) n: 1639, 1578, 1507,
1487, 1472, 1361, 1262, 1221, 1177, 1119, 1097, 1013, 848 cmꢂ1. Anal.
calcd. for C29H29ClFNO2: C, 72.87; H, 6.12; N, 2.93; found: C, 72.98;
H, 6.03; N, 2.96.
3,3,6,6-Tetramethyl-9-(4-bromophenyl)-10-(4-chlorophenyl)-
1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione (4g)
Mp 258–260 ꢀC; 1H NMR (DMSO-d6) d: 0.72 (6H, s, 2 ꢁ CH3), 0.89 (6H,
s, 2 ꢁ CH3), 1.78 (2H, d, J ¼ 17.2 Hz, 2 ꢁ CH), 2.01 (2H, d, J ¼ 16.0 Hz,
2 ꢁ CH), 2.19 (4H, d, J ¼ 17.2 Hz, 4 ꢁ CH), 4.99 (1H, s, CH), 7.26 (2H,
d, J ¼ 8.0 Hz, ArH), 7.44 (2H, d, J ¼ 8.4 Hz, ArH), 7.46–7.54 (2H, m,
ArH), 7.69 (2H, d, J ¼ 8.0 Hz, ArH); 13C NMR (DMSO-d6) d: 26.09,
29.21, 31.99, 40.89, 49.48, 112.61, 118.80, 129.88, 130.14, 130.80,
130.94, 133.99, 137.19, 145.49, 150.35, 195.09; IR (KBr) n: 1639, 1577,
1490, 1360, 1302, 1263, 1220, 1178, 1145, 1119, 1089, 1008, 739 cmꢂ1
.
Anal. calcd. for C29H29BrClNO2: C, 64.63; H, 5.42; N, 2.60; found: C,
64.46; H, 5.37; N, 2.66.
3-Hydroxy-30-(4-chlorophenylamino)(4-bromophenylmenthylene)bis(5,5-
dimethyl-2-cyclohexene-1-one-2-yl) (5g)
1
Mp 178–180 ꢀC; H NMR (DMSO-d6) d: 0.88 (3H, s, CH3), 1.04 (6H, s,
2 ꢁ CH3), 1.12 (3H, s, CH3), 2.17 (1H, d, J ¼ 16.4 Hz, CH), 2.29–2.43
(6H, m, 6 ꢁ CH), 2.59 (1H, d, J ¼ 16.4 Hz, CH), 5.60 (1H, s, CH), 7.11
(2H, d, J ¼ 8.4 Hz, ArH), 7.20–7.37 (6H, m, ArH), 9.99 (1H, s, NH),
12.97 (1H, s, OH); 13C NMR (DMSO-d6) d: 27.50, 28.07, 30.69, 31.41,
32.59, 32.90, 43.64, 49.26, 109.99, 111.27, 113.46, 118.09, 125.73, 128.98,
129.31, 129.68, 130.64, 136.76, 137.29, 139.68, 196.59, 200.02; IR (KBr)
n: 3242, 3044, 1585, 1485, 1382, 1326, 1291, 1278, 1238, 1155, 1088,
1075, 1039, 889, 863, 826, 709 cmꢂ1. Anal. calcd. for C29H31BrClNO3:
C, 62.54; H, 5.61; N, 2.52; found: C, 62.61; H, 5.56; N, 2.48.
Crystal Data
Compound 4a
C31H33NO5; M ¼ 499.58, colorless block crystals, 0.24 ꢁ 0.22 ꢁ 0.12 mm,
monoclinic, space group P21=c, a ¼ 12.1854(18), b ¼ 11.3687(18),

Synthesis of Polyhydroacrodine Derivatives
673
3
ꢀ
ꢀ
ꢀ
˚
˚
c ¼ 19.609(3) A, a ¼ 90 , b ¼ 101.62 (3) , c ¼ 90 , V ¼ 2660.7(7) A , Z ¼ 4,
Dc ¼ 1.247 g=cm3, F (000) ¼ 1064, l(MoKa) ¼ 0.084 mmꢂ1. Intensity data
were collected on Smart-1000 diffractometer with graphite monochro-
˚
mated MoKa radiation (k ¼ 0.71073 A) using x scan mode with
2.08ꢀ < h < 25.01ꢀ; 5457 unique reflections were measured, and 2849
reflections with I > 2r (I) were used in the refinement. The structure
was solved by direct methods and expanded using the Fourier technique.
The final cycle of full-matrix least squares technique showed R ¼ 0.0460
and wR ¼ 0.1011.
Compound 5a
C31H35NO6; M ¼ 517.60, colorless block crystals, 0.39 ꢁ 0.18 ꢁ 0.16 mm,
triclinic, space group P-1, a ¼ 11.691(12), b ¼ 14.362(14), c ¼ 17.253(17)
3
ꢀ
ꢀ
ꢀ
˚
˚
A, a ¼ 94.765(18) , b ¼ 90.721(17) , c ¼ 100.817(18) , V ¼ 2834(5) A ,
Z ¼ 4, Dc ¼ 1.213 g=cm3, F (000) ¼ 1104, l(MoKa) ¼ 0.084 mmꢂ1. Inten-
sity data were collected on Smart-1000 diffractometer with graphite
˚
monochromated MoKa radiation (k ¼ 0.71073 A) using x scan mode with
2.11ꢀ < h < 25.01ꢀ; 9835 unique reflections were measured, and 5861
reflections with I > 2r (I) were used in the refinement. The structure
was solved by direct methods and expanded using Fourier technique.
The final cycle of full-matrix least squares technique showed
R ¼ 0.0591 and wR ¼ 0.1548.
ACKNOWLEDGMENTS
We are grateful to the Foundation of Key Laboratory of Biotechnology
on Medical Plants of Jiangsu Province for financial support.
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