One pot synthesis of α-aminophosphonates containing bromo and 3,4,5-trimethoxybenzyl groups under solvent-free conditions

Article abstract of DOI:10.3390/12020163

New α-aminophosphonates were synthesized by the Kabachnik-Fields reaction of 3,4,5-trimethoxybenzaldehyde (TMB) with p- or m-bromoaniline and a dialkyl phosphite under solvent-free conditions. TMB was prepared from gallic acid via a four step synthetic sequence involving etherification, esterification, hydrazidation and potassium ferricyanide oxidation. The structures of all synthesized compounds were confirmed by elemental analysis, IR, ¹H-, ¹³C- and ³¹P-NMR spectral data. Compound 7g was also characterized by X-ray crystallography. A half-leaf method was used to determine the in vivo curative efficacy of the eight title products against tobacco mosaic virus (TMV). It was found that compounds 7g and 7h possess good in vivo curative effects against TMV.

Full text of DOI:10.3390/12020163

Molecules 2007, 12, 163-172
molecules
ISSN 1420-3049
http://www.mdpi.org
Full Paper
One Pot Synthesis of α-Aminophosphonates Containing Bromo
and 3,4,5-Trimethoxybenzyl Groups under Solvent-free
Conditions
Caihong Li, Baoan Song*, Kai Yan, Gangfang Xu, Deyu Hu, Song Yang, Linhong Jin, Wei Xue
and Ping Lu
Center for Research and Development of Fine Chemicals, Guizhou University, Key Laboratory of
Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guiyang, 550025, P. R.
China. E-mails:licaihong2004@163.com, lk81@163.com, xuguangf04@163.com,
fcc.dyhu@gzu.edu.cn, yangsdqj@126.com, fcc.lhjin@gzu.edu.cn, shouldww@163.com,
luping217@sohu.com
*
Author to whom correspondence should be addressed; E-mail:songbaoan22@yahoo.com; Tel.: (+86)
51 3620521, Fax: (+86) 851 3622211
8
Received: 26 Jan 2007; in revised form: 6 February 2007 / Accepted: 6 February 2007 / Published:
February 2007
7
Abstract: New α-aminophosphonates were synthesized by the Kabachnik-Fields reaction
of 3,4,5-trimethoxybenzaldehyde (TMB) with p- or m-bromoaniline and a dialkyl
phosphite under solvent-free conditions. TMB was prepared from gallic acid via a four
step synthetic sequence involving etherification, esterification, hydrazidation and
potassium ferricyanide oxidation. The structures of all synthesized compounds were
1
13
31
confirmed by elemental analysis, IR, H-, C- and P-NMR spectral data. Compound 7g
was also characterized by X-ray crystallography. A half-leaf method was used to
determine the in vivo curative efficacy of the eight title products against tobacco mosaic
virus (TMV). It was found that compounds 7g and 7h possess good in vivo curative
effects against TMV.
Keywords: α-Aminophosphonates; bromo group; 3,4,5-trimethoxybenzyl group;
Kabachnik-Fields reaction; solvent-free conditions; crystallography; biological activity.

Molecules 2007, 12
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Introduction
α-Aminophosphonates, structural analogues of natural amino acids, have received wide attention
in medicinal, bioorganic and organic chemistry. The applications of α-aminophosphonates have ranged
from agriculture to medical uses as anti-cancer agents [1], enzyme inhibitors [2], peptide mimetics [3],
antibiotics and pharmacological agents [4]. To the best of our knowledge, only a few α-aminophosphonates
containing bromo and 3,4,5- trimethoxybenzyl groups have been reported. As typical of a halogen, bromine has
high electronegativity and is also known for its steric and lipophilic effects. As an active group, bromine is
often introduced in the design of bioactive compounds. Many pesticides containing bromine are widely
used commercially, and have a broad spectrum of activity, high efficiency and low toxicity, associated
with their easy decomposition and minimal residues [5].
Gallic acid derivatives are compounds of significant biological and pharmaceutical interest [6-8].
Among them, 3,4,5-trimethoxybenzaldehyde (TMB) is an important pharmaceutical intermediate,
which is employed, among other examples, in the synthesis of trimethoprim, tretoquinol and
podophyllotoxin [9].
In view of all this information, a series of α-aminophosphonates containing bromo and 3,4,5-
trimethoxybenzyl groups were designed and synthesized in our laboratory for the purpose of exploring
them as potential bioactive compounds. Substituted α-aminophosphonates are often synthesized in an organic
solvent via a traditional Kabachnik-Fields reaction [10], but the use of organic solvents has a serious
impact on the environment, whereas in contrast, solvent free reactions are benign and do not call for
any drastic work-ups.
Herein we report an easy one pot an easy one pot synthesis of new α- aminophosphonates 7a-7g by
Kabachnik-Fields reaction of equimolar mixtures of 3,4,5-trimethoxybenzaldehyde (TMB) and p- or m-
bromoaniline with dialkyl phosphite under solvent-free conditions (Scheme 1).
Scheme 1. Synthesis of compounds 7a-7h by the Kabachnik-Fields reaction..
H CO
H CO
R2
3
3
O
H
OR1
105~110℃
H CO
CHO +
NH2
+
P
H CO
CH NH
3
3
Solvent-free
OR1
P OR1
OR1
R2
O
H CO
H CO
3
3
4
5
6
7
R = m-Br, p-Br
R = Et, i-Pr, n-Pr, n-Bu
1
2
The TMB starting material 4 was prepared in turn in high yield from gallic acid (abundant in plant
gallnut) in four steps: etherification, esterification, hydrazidation and potassium ferricyanide oxidation
Scheme 2).
(

Molecules 2007, 12
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Scheme 2. Synthesis of the starting material 4 from gallic acid.
HO
HO
H CO
H CO
3
3
(
CH ) SO
3 2 4
CH OH
3
COOH
H CO
COOH
H CO
COOCH3
3
3
NaOH
H SO
2
4
HO
H CO
H CO
3
3
1
2
H CO
H CO
3
3
NH NH .H O
2
2
2
NH .H O
3 2
H CO
CONHNH2
H CO
CHO
3
3
K Fe(CN)
3
6
H CO
H CO
3
3
3
4
Results and Discussion
A systematic study of the effect of reaction parameters on the process, including reaction
temperature, the molar ratios of reagents and the amount of catalyst, was undertaken for optimization
of the reaction. For this purpose, compound 7g was synthesized under different conditions.
First, the effect of reaction temperature was investigated. When the reaction temperature was
increased from 85~90 °C to 95~100 °C and then to 105~110°C, the yields obtained were 37.5 %, 61.2
%
and 65.6 %, respectively (Table 1, entries 1-3). When the temperature was further increased to
15~120°C, no improvement was noticed (56.3 %, Table 1, entry 4), compared to the results obtained
at 105~110°C (entry 3). Next, the effect of molar ratio of the reagents was investigated at the
05~110°C temperature. As the molar ratio of the reagents (dialkyl phosphate/amine/aldehyde) was
varied from 1:1:1, 1.2:1:1 to 2:1:1, no significant changes were observed in the yields (65.6%, 61.8 %,
1
1
6
0.3%, respectively Table 1, entries 3, 5 and 6).
The yield of the product was found to be significantly lower under otherwise similar conditions
when no catalyst was used (Table 2, entry 2). The yield was improved as the amount of catalyst was
increased from 5 mol% to 10 mol% (Table 2, entries 3, 4), but no noteworthy change was observed
when the amount of catalyst used was increased to 15 mol% (Table 2, entry 5). Based on these results,
the optimal conditions for the synthesis was established as the use of equivalent molar concentrations
3 2
of the reactants and 10 mol% BF ·Et O with a reaction temperature of 105~110 °C and a reaction time
of 30 min.
Table 1. The influence of the molar ratio of reagents and the reaction
temperature on the synthesis of 7a.
Dialkyl phosphate: amine:
aldehyde
Reaction
time
Reaction temperature
°C)
Yield
(%)
Entry
(
(
molar ratio)
1:1:1
(h)
2
1
2
3
4
5
6
85~90
37.5
61.2
65.6
56.3
61.8
60.3
1:1:1
95~100
2
1:1:1
105~110
115~120
105~110
105~110
2
1:1:1
2
1.2:1:1
2:1:1
2
2

Molecules 2007, 12
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Table 2. The influence of the amount of catalyst BF ·Et O on the synthesis of 7a.
3
2
Dialkyl phosphate:
amine: aldehyde
Amount of
catalyst
Reaction
time
Yield
%)
Entry
Catalyst
(
(
molar ratio)
1:1:1
(mol %)
(min.)
120
30
1
2
3
4
5
-
-
-
-
65.6
41.0
66.6
76.0
71.7
1:1:1
1:1:1
BF
BF
BF
3
·Et
·Et
·Et
2
O
5
30
1:1:1
3
2
O
10
15
30
1:1:1
3
2
O
30
.
3 2
As may be seen from Table 3, using optimal conditions and with 10 mol% BF Et O catalyst, the
compounds 7a-7h could be obtained in high yields (70.6-83.5%) after a much shorter reaction time (30
min). The compounds 7a-7h were obtained in 61.3-74.2% yield when the reaction was conducted for
longer periods of time (2 h), but without the use of a catalyst.
Table 3. Yields of 7a-7h.
Substitutents
With Catalyst
Reaction time Yield
Without Catalyst
Reaction time
Compounds
R1
R2
Yield (%)
(
min.)
(%)
76.0
(h)
7
7
a
Et
Et
p-Br
m-Br
p-Br
m-Br
30
2
65.6
61.5
67.8
71.0
62.5
61.4
74.2
61.3
b
30
30
30
30
30
30
30
75.9
82.0
81.0
76.1
70.6
83.5
75.8
2
2
2
2
2
2
2
7
c
i-Pr
i-Pr
7
d
n-Bu p-Br
n-Bu m-Br
7
e
7
f
7
7
g
n-Pr
p-Br
n-Pr m-Br
h
1
13
The structures of compounds 7a-7h were identified by elemental analysis, IR, H-, C- and
3
1
-1
P-NMR spectral data. Taking compound 7g as an example, the absorption band at 3400 cm (s) in its
-1
-1
IR spectrum corresponds to an N-H stretch, the absorption bands at 1240 cm (s) and 1001 cm (s)
1
correspond to P=O and P-O-C stretching, respectively. The H-NMR spectra of 7g showed
well-resolved doublets at δ 4.64 (JP-H = 24.05 Hz) for the P(O)CH proton, while a singlet at δ 3.04 was
3
1
due to the presence of the NH proton. In the P-NMR spectra the phosphonate group resonance
appeared at δp 22.69. The structure of compound 7g was definitively confirmed by X-ray diffraction
analysis.
Crystal Structure Analysis of 7g.
The crystal belongs to the tetragonal system with space group P 2(1)/c, a = 12.7429(14) nm, b =
3
1
4.1740(16) nm, c = 4.2643(15) nm, α = 90.00°, β = 107.360(6) °, γ = 90.00°, V = 2459.0(5) nm , Z =

Molecules 2007, 12
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3
-1
4
, Dc = 1.395 mg/m , µ = 1.77 mm , F (000) = 1072.0. The molecular structure and cell packing of
the compound are presented in Figures 1 and 2, respectively. It can be seen from Figure 1 that the two
phenyl rings are planar, with a C(4)-C(5)-C(7)-N(1) torsion angle of about 56.58°. As shown in Figure
…
2
2
, there is one N -H O hydrogen bond intermolecular interaction. The N(1)-O(4) bond distance is
…
.960 nm and N(1)-H(1) O(4) bond angle is 165.94° (Table 4). In the solid state, the hydrogen bonds
form a two-dimensional network to stabilize the crystal structure.
Figure 1. Molecular structure of compound 7g.
Figure 2. Cell packing of the compound 7g.
Table 4. Hydrogen bonds for compound 7g.
…
D-H A
d(D-H)/nm
d(H-A)/nm
d(D-A)/nm
∠DHA(°)
…
N(1)-H(1) O(4)
0.860
2.118
2.960
165.94
*
Symmetry transformations used to generate equivalent atoms: #1: -x+1, -y, -z+2

Molecules 2007, 12
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Antiviral activity bioassays
The results of the in vivo activity against TMV bioassays are given in Table 5. Ningnanmycin was
used as reference antiviral agent. The data indicate that a change in the substituent might also affect the
curative activity of title compounds 7a-7h. Compound 7h (R = n-Pr, R =3-Br) and compound 7g (R =
1
2
1
n-Pr, R =4-Br) could cure TMV up to 54.5% and 44.3% at 500µg/mL. The other compounds all have
2
relatively lower curative activity than 7h and 7g.
Table 5. The curative effect of title compounds 7a-h at 500 µg/mL against TMV.
Compd.
7a
7b
7c
7d
7e
7f
7g
7h
Ningnamycin
Inhibition rate (%)
35.0 23.8 28.0 26.2 22.5 11.7 44.3 54.5 57.5
Conclusions
A series of α-aminophosphonates 7a-h containing bromo and 3,4,5-trimethoxybenzyl groups were
synthesized by Kabachnik-Fields reaction under solvent-free condition. The procedure offers a great
alternative to existing methodologies due to its ease of work up, faster reaction rates and high yields.
The method is clean, free of any significant byproducts, environmental friendly and does not employ
any solvent. A half-leaf method was used to determine the curative efficacy in vivo of the eight title
products against tobacco mosaic virus (TMV). It was found that compound 7h had a good curative
effect in vivo against TMV, with an inhibition rate of 54.5%.
Acknowledgements
We thank the National Natural Science Foundation of China (No: 20362004) and the Foundation
for New Century Excellent Talent in the Universities of China (Grant No. NCET-04-0912) for financial
support of this work.
Experimental
General
Melting points (uncorrected) were measured on a XT-4 binocular microscope (Beijing Tech
Instrument Co., China). The IR spectra (KBr disks) were recorded on a Bruker VECTOR 22
1
13
spectrometer. H- and C-NMR spectra were determined at room temperature in the indicated solvents
1
13
on a JEOL-ECX 500 NMR spectrometer (500 MHz for H and 125 MHz for C), with TMS as
3
1
internal standard. P-NMR spectra were measured using as external reference an 85% H
prepared by sealing a capillary containing 85% H PO in a 5 mm NMR tube containing a suitable
amount of CDCl for field locking. Elemental analysis was performed on an Elementar Vario-III CHN
3 4
PO sample
3
4
3
analyzer. The reagents were all of analytical reagent grade or chemically pure. All solvents were dried,
deoxygenated and redistilled before use. TMB was prepared from gallic acid according to literature

Molecules 2007, 12
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69
methods [11-13]. O,O-Dialkyl phosphites were prepared as described in the literature [14].
General procedure for the preparation of products 7a-h
A mixture of 3,4,5-trimethoxybenzaldehyde (3 mmol), p- (or m-) bromoaniline (3 mmol) and
dialkyl phosphite (3 mmol) was stirred in silicone oil bath at 108 °C for 2 h. The reaction was followed
and monitored by TLC (petroleum ether-ethyl acetate=1:2 v/v). The resultant viscous liquid was
dissolved in ether and then washed, first with saturated aqueous NaHCO and next with distilled water.
3
The organic layer was separated, followed by extraction of the aqueous layer with ethyl acetate (3×10
4
mL). The combined organic layers were dried over MgSO and concentrated under reduced pressure.
The residue was purified by recrystallization from petroleum ether to give compounds 7a-7h as white
crystals. At the same time, compounds 7a-7h were also synthesized using BF ·Et O as catalyst by a
3
2
similar procedure.
Yields and physicochemical properties:
O,O’-diethyl-α-(4-bromophenylamino)-3,4,5-trimethoxybenzylphosphonate (7a). M.p. 123-124 °C; IR:
-
1 1
3
398.6, 1591.3, 1242.2, 1055.1, 1029.9 cm ; H-NMR (CD
d, J= 24.0 Hz, 1H, CH-P), 3.95-4.15 (m, 4H, 2OCH ), 3.69-3.79 (m, 9H, 3OCH
) δ: 16.75, 55.30, 56.42, 56.52, 60.49, 63.59,
3
OCD
3
) δ: 6.82-7.18 (m, 6H, Ar-H), 4.65
(
2
3
), 3.06 (br s, 1H,
1
3
3 3 3
NH), 1.12-1.27 (m, 6H, 2CH ); C-NMR (CD OCD
3
1
1
06.71, 109.51, 116.53, 132.34, 132.75, 138.63, 147.60, 154.23; P-NMR δ: 22.78; Anal. Calcd. for
P(488.31): C, 49.19; H, 5.57; N, 2.87. Found C, 49.28; H, 5.54; N, 3.09.
20 6
C H27BrNO
O,O’-diethyl-α-(3-bromophenylamino)-3,4,5-trimethoxybenzylphosphonate (7b). M.p. 113-114 °C; IR:
-
1 1
3
305.9, 1591.3, 1228.7, 1047.4, 1022.3 cm ; H-NMR (CD
d, J=24.6Hz, 1H, CH-P), 3.93-4.16 (m, 4H, m, 2OCH ), 3.69-3.79 (m, 9H, 3OCH
) δ: 16.77, 55.04, 56.26, 56.44, 60.52, 63.65,
3
OCD
3
) δ: 6.96-7.08 (m, 6H, Ar-H), 4.66
(
2
3
), 3.07 (br s, 1H,
1
3
3 3 3
NH), 1.13-1.27 (m, 6H, 2CH ); C-NMR (CD OCD
3
1
1
06.77, 113.30, 117.28, 120.91, 123.34, 131.36, 132.74, 138.71, 149.88, 154.23; P-NMR δ: 22.65;
Anal. Calcd. for C H BrNO P(488.31): C, 49.19; H, 5.57; N, 2.87. Found C, 49.24; H, 5.40; N, 3.00.
2
0
27
6
O,O’-di-i-propyl-α-(4-bromophenylamino)-3,4,5-trimethoxybenzylphosphonate (7c). M.p. 134-135 °C;
-
1 1
IR: 3284.8, 1591.3, 1228.7, 1001.1 cm ; H-NMR (CDCl
3
) δ: 6.47-7.21 (m, 6H, Ar-H), 4.68-4.50 (m,
), 3.08 (br s, 1H, NH), 1.00-1.23 (m, 12H, 4CH );
3
) δ: 23.47, 24.35, 56.24, 56.39, 57.60, 60.95, 72.31, 104.94, 110.29, 115.50, 131.46,
3
H, CH-P+2OCH), 3.82-3.83 (m, 9H, m, 3OCH
3
3
1
3
C-NMR (CDCl
3
1
1
5
6
32.00, 137.74, 145.83, 153.36; P-NMR δ: 20.99; Anal. Calcd. for C22H31BrNO P (516.36): C,
1.17; H, 6.05; N, 2.71. Found C, 51.38; H, 6.14; N, 2.95.
O,O’-di-i-propyl-α-(3-bromophenylamino)-3,4,5-trimethoxybenzylphosphonate (7d). M.p. 123-124°C;
-
1 1
IR: 3278.9, 1591.3, 1228.7, 1008.8 cm ; H-NMR (CDCl
H, CH-P+2OCH), 3.82-3.84 (m, 9H, m, 3OCH ), 3.08 (br s, 1H, NH), 0.98-1.22 (m, 12H, 4CH
NMR (CDCl ) δ: 23.95, 24.35, 56.10, 56.25, 57.31, 60.96, 72.33, 106.77, 112.44, 116.65, 121.32,
3
) δ: 6.52-6.98 (m, 6H, Ar-H), 4.48-4.58 (m,
1
3
3
3
3
); C
-
3
3
1
1
6
23.16, 130.56, 131.40, 137.76, 148.01, 154.23; P-NMR δ: 20.88; Anal. Calcd. for C22H31BrNO P
(516.36): C, 51.17; H, 6.05; N, 2.71. Found C, 51.31; H, 5.98; N, 2.81.

Molecules 2007, 12
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O,O’-di-n-butyl-α-(4-bromophenylamino)-3,4,5-trimethoxybenzylphosphonate (7e). M.p. 87-88°C; IR:
-
1
1
3
2
1
5
278.9, 1591.3, 1226.7, 1018.4 cm ; H-NMR (CDCl ) δ: 6.48-7.21 (m, 6H, Ar-H), 4.62 (d, J＝
3
3.50Hz, 1H, CH-P), 3.94-4.05 (m, 4H, 2OCH
2 3
), 3.84-3.90 (m, 9H, 3OCH ), 3.08 (br s, 1H, NH),
13
.24-1.61 (m, 8H, 4CH ), 0.84-0.88 (m, 6H, 2CH ); C-NMR (CDCl ) δ:13.63, 18.74, 32.60, 55.85,
2
3
3
3
1
6.21, 57.06, 60.91, 67.07, 104.71, 110.38, 115.52, 131.21, 132.02, 137.76, 145.61, 153.50; P-NMR
P (544.42): C, 52.95; H, 6.48; N, 2.57. Found C, 53.06; H,
δ: 22.75; Anal. Calcd. for C24
.42; N, 2.73.
H35BrNO
6
6
O,O’-di-n-butyl-α-(3-bromophenylamino)-3,4,5-trimethoxybenzylphosphonate (7f). M.p. 80-81°C; IR:
-1 1
3
304.1, 1591.3, 1238.3, 1026.1 cm ; H-NMR (CDCl ) δ: 6.50-7.21 (m, 6H, Ar-H), 4.63 (d, J =23.50
3
Hz, 1H, CH-P), 3.95-4.05 (m, 4H, 2OCH
2
), 3.84-3.91 (m, 9H, 3OCH
3
), 3.04 (br s, 1H, NH), 1.25-1.61
1
3
(
m, 8H, 4CH
2
), 0.84-0.90 (m, 6H, 2CH
3
); C-NMR (CDCl
3
) δ: 13.56, 18.68, 32.40, 55.52, 56.16,
5
6.73, 60.84, 66.99, 104.75, 112.39, 116.56, 121.34, 123.09, 130.49, 131.11, 137.73, 147.84, 53.44;
3
1
6
P-NMR δ: 22.65; Anal. Calcd. for C24H35BrNO P (544.42): C, 52.95; H, 6.48; N, 2.57. Found C,
5
2.97; H, 6.44; N, 2.67.
O,O’-di-n-propyl-α-(4-bromophenylamino)-3,4,5-trimethoxybenzylphosphonate (7g). M.p. 111-112°C;
-1 1
IR: 3400.5, 1591.3, 1240.2, 1001.1 cm ; H-NMR (CDCl ) δ: 6.50-7.21 (m, 6H, Ar-H), 4.64 (d, J=
3
2
1
5
2
4.05 Hz, 1H, CH-P), 3.93-4.01 (m, 4H, 2OCH
.51-1.67 (m, 4H, 2CH ), 0.82-0.92 (m, 6H, 2CH
7.06, 60.91, 68.82, 104.73, 110.38, 115.52, 131.20, 132.01, 137.77, 145.61, 153.49; P-NMR δ:
2.69; Anal. Calcd. for C22 P (516.36): C, 51.17; H, 6.05; N, 2.71. Found C, 51.25; H, 5.79;
2
), 3.81-3.83 (m, 9H, 3OCH
3
), 3.04 (br s, 1H, NH),
1
3
2
); C-NMR (CDCl ) δ: 9.97, 23.96, 55.85, 56.23,
3 3
3
1
H31BrNO
6
N, 2.76%.
O,O’-di-n-propyl-α-(3-bromophenylamino)-3,4,5-trimethoxybenzylphosphonate (7h). M.p. 85-86°C;
-
1 1
IR: 3305.9, 1591.3, 1234.4, 1002.9 cm ; H-NMR (CDCl
3
) δ: 6.51-6.97 (m, 6H, Ar-H), 4.66 (d, J=
), 3.84-3.86 (m, 9H, 3OCH ), 3.07 (br s, 1H, NH),
.50-1.67 (m, 4H, 2CH ), 0.84-0.92 (m, 6H, 2CH ); C-NMR (CDCl ) δ: 9.98, 23.97, 55.58, 56.24,
2
1
5
3.45 Hz, 1H, CH-P), 3.92-4.02 (m, 4H, 2OCH
2
3
1
3
2
3
3
6.79, 60.91, 68.81, 104.86, 112.43, 116.67, 121.37, 123.15, 130.56, 131.81, 147.96, 153.49;
3
1
6
P-NMR δ: 22.59; Anal. Calcd. for C22H31BrNO P (516.36): C, 51.17; H, 6.05; N, 2.71. Found C,
5
1.26; H, 5.95; N, 2.66.
X-Ray diffraction experiment
The X-ray diffraction data of compound 7g were collected at 293(2)K on a Rigaku Raxis-IV
diffractometer with graphite-monochromated MoKa (λ=0.71073Å) radiation using an ω scan mode in
the 1.67º≤θ≤24.99º range. A total of 8805 reflections were collected and 3737 were independent (Rint
=
0.0288), of which 2577 with I > 2σ (I) were observed. The crystal structure was solved by the direct
method and refined by full-matrix least squares with the SHELXS-97 program [15]. The non-hydrogen
atoms were refined on F2 anisotropically, and the hydrogen atoms were determined with theoretical
2
2
2
calculation. The least-square cycle gave R = 0.0461, wR = 0.1317 (w =1 / [σ (F
o
) + ( 0.0884 P )
2
2
+
1.2039 P ], where P = ( F
o
+ 2 F
c
)/3.), S = 0.970, (∆/σ) max = 0.005, (∆ρ)max=0.83 and (∆ρ)min
=
3
-
0.59e/Å . Atomic scattering factors and anomalous dispersion corrections were taken from

Molecules 2007, 12
1
71
International Table for X-ray Crystallography [16]. Crystallographic data (excluding structure factors)
for the structure have been deposited with the Cambridge Crystallographic Data Center as
supplementary publication No. CCDC-634425. These data can be obtained free of charge from the
CCDC via www.ccdc.cam.ac.uk/data_request/cif.
Antiviral Bioassay
Nicotiana tabacum. L leaves of the same age were selected. Whole leaves were dipped in a
-3
solution containing tobacco mosaic virus (6×10 mg/mL), then the leaves were washed with water and
dried. The test compound solution was smeared on the left side and the solvent was smeared on the
right side for control. The local lesion numbers were then recorded 3-4 days after inoculation [17]. For
each compound, three repetitions were carried out to ensure the reliability of the results. Inhibition
rates were calculated using the expression:
Inhibition rate (%) = av local lesion numbers of control (not treated with compound) − av local lesion numbers smeared with drugs
av local lesion numbers without drugs
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Sample Availability: Samples of the compounds are available from authors.
2007 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.
©