Syntheses, structures and bioactivities of fluorine-containing phenylimino-thia(oxa)zolidine derivatives as agricultural bioregulators

Article abstract of DOI:10.1016/j.jfluchem.2004.09.002

From insight into the structure of trehazolin as trehalase inhibitor, six series of fluorine-containing phenylimino-thiazolidines (oxazolidines) derivatives were designed and prepared through a convenient synthesis of fluoroaryl isothiocyanate and a one-pot facile synthesis in high yield of fluorophenyl aminobenzoxazoles by cyclodesulfurization. The structures of the target compounds were confirmed with using IR, NMR, MS and elemental analysis. Their X-ray crystal analysis suggested that there were novel intermolecular (sp²CF?H₃C) and intramolecular (sp ²CF?HN) hydrogen bonds between the fluorine atom on benzene ring and hydrogen atom of methyl group or amino group on five-membered heterocycle. Their fungicidal activities against Rhizoctonia solani and Pyricuraria oryzae at 100 ppm were determined. From insight into the structure of trehazolin as trehalase inhibitor, six series of fluorine-containing phenylimino-thiazolidines (oxazolidines) derivatives were designed and prepared through a convenient synthesis of fluoroaryl isothiocyanate and a one-pot facile synthesis in high yield of fluorophenyl aminobenzoxazoles by cyclodesulfurization. The structures of the target compounds were confirmed with using IR, NMR, MS and elemental analysis. Their X-ray crystal analysis suggested that there were novel intermolecular (sp²CF?H ₃C) and intramolecular (sp²CF?HN) hydrogen bonds between the fluorine atom on benzene ring and hydrogen atom of methyl group or amino group on five-membered heterocycle. Their fungicidal activities against Rhizoctonia solani and Pyricuraria oryzae at 100 ppm were determined. fx1

Full text of DOI:10.1016/j.jfluchem.2004.09.002

Journal of Fluorine Chemistry 125 (2004) 1609–1620
www.elsevier.com/locate/fluor
Syntheses, structures and bioactivities of fluorine-containing
phenylimino-thia(oxa)zolidine derivatives as
agricultural bioregulators
a,
Xuhong Qian , Xiaoyong Xu , Zhibin Li , Zhong Li , Gonghua Song
b
b
b
b
*
aState Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China
bShanghai Key Laboratory of Chemical Biology, Institute of Pesticides and Pharmaceuticals,
East China University of Science and Technology, Shanghai 200237, China
Available online 22 October 2004
Abstract
From insight into the structure of trehazolin as trehalase inhibitor, six series of fluorine-containing phenylimino-thiazolidines
(oxazolidines) derivatives were designed and prepared through a convenient synthesis of fluoroaryl isothiocyanate and a one-pot facile
synthesis in high yield of fluorophenyl aminobenzoxazoles by cyclodesulfurization. The structures of the target compounds were confirmed
with using IR, NMR, MS and elemental analysis. Their X-ray crystal analysis suggested that there were novel intermolecular (sp2CF ꢀ ꢀ ꢀ H3C–)
and intramolecular (sp2CF ꢀ ꢀ ꢀ HN) hydrogen bonds between the fluorine atom on benzene ring and hydrogen atom of methyl group or amino
group on five-membered heterocycle. Their fungicidal activities against Rhizoctonia solani and Pyricuraria oryzae at 100 ppm were
determined.
# 2004 Elsevier B.V. All rights reserved.
Keywords: Fluoro group; Phenylimino-thiazolidine (oxazolidine); Agricultural bioregulators; Hydrogen bonding
1. Introduction
complicated and their syntheses were very difficult.
Shiozaki reported that trehazolin was obtained from a 15-
step synthesis starting from D-glucose, which was a
convergent strategy [8–12]. In addition, trehazolin and its
analogues had high inhibition activities in vitro, and only
showed low activities in vivo because of too many
hydrophilic hydroxyl groups in their structures. So far
there have been few reports about an unnatural product, e.g.
fluorinated compound, which mimic trehazolin as trehalase
inhibitor to show fungicidal activities, which have relatively
simple structures and can be prepared easily.
Natural trehazolin, just like Validamycin A [1] that has
been commercialized and is used to control blight sheath of
rice caused by the plant pathogenic fungus Rhizoctonia
solani, is a slow- and tight-binding inhibitor of trehalase [2].
Trehazolin also shows potential fungicidal activity to control
R. solani at 100 ppm [3].
Trehalase is a very specific enzyme that hydrolyzes
trehalose, which is a main source of glucose in insects and
fungi, to two glucose units and is widely distributed in
microorganisms, insects, plants and animals [13,2]. Besides
trehazolin [14] some other trehalase inhibitors have been
isolated from natural sources, such as deoxynojirimycin
[15], salbostain [16], validamycins [17], and validoxyla-
mines [18]. Of course, trehazolin is the most potent one
among natural products. A notable feature of this inhibition
Recently, a variety of the reports regarding synthesis or
modification of the trehazolin derivatives have been
presented due to the chemical and biological interests
[2,4–7]. But, the structure of trehazolin and its analogues are
* Corresponding author. Tel.: +86 4113673466; fax: +86 4113673488.
E-mail address: xhqian@dlut.edu.cn (X. Qian).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2004.09.002

1610
X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
Fig. 1. The structures of designed compounds 1–6.
Scheme 1.
is the formation of trehazolin–trehalase complex through the
bridgehead nitrogen in trehazolin and the carbonyl group in
trehalase [19], and the hydroxyl groups in trehazolin were
topologically essential for its tight binding to the active sites
of trehalase through hydrogen bonds [20]. It is well known
that fluorine-containing compounds usually exhibit sig-
nificant agricultural bioactivity owing to their unique
property, such as high thermal stability, lipophilicity and
ability to form hydrogen bonds with the active site of some
enzyme [21]. The incorporation of polyfluorophenyl groups
would increase the precursor’s hydrophobicity and pene-
trating ability. Thus, on the basis of trehazolin structural
model (a N=C–N unit, heterocyclic moiety and polyhy-
droxyl groups) [20,21] six series of fluorine-containing
compounds including phenylimino-thiazo(oxazo)lidines (1–
3) [22,23], phenylimino-benzoxazolidines (4) [24], N,N0-
diphenyl carbamidothioates (5), and pyranoaniline deriva-
tives (6) [25] were designed and synthesized, their structures
and fungicidal activities were also investigated. The
structures of 1–6 are shown in Fig. 1.
2. Results and discussion
2.1. Synthesis of fluorophenyl imino-thiazo(oxazo)lidines
and analogues
By a facile and convenient method, novel fluorine-
containing phenylimino-thiazo(oxazo)lidines (1–3) were
synthesized as shown in Schemes 1 and 2. Phenylimino-
Scheme 2.

X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
1611
Scheme 3.
Scheme 4.
benzoxazolidines (4), N,N0-diphenyl carbamidothioates (5),
pyranoaniline derivatives (6) were prepared as shown in
Schemes 3–5, respectively. The substituents of compounds
1–6 are listed in Table 1. The structures of compounds 1–6
were confirmed by using NMR, IR, MS and elemental
analysis [22–25,31,36], which are listed in Table 2.
was provided here for fluoroaryl isothiocyanates from
fluoroarylamines in the presence of CS2, NaOH and
ClCOOEt (Scheme 6) [31].
2-Aryl aminobenzoxazoles were generally synthesized
by cyclodesulfurization of N-(2-hydroxyphenyl)-N0-phe-
nylthioureas with nickel peroxide [32], potassium super-
oxide [33] and dicyclohexylcarbodiimide [34], or by
treatment of 2-chlorobenzoxazole with aniline in THF
[35]. It was also very difficult for us to synthesize
fluorophenyl aminobenzoxazoles with using the known
synthetic method for non-fluoro-counterpart, as the presence
of too strong electron-withdrawing fluoro-group. From the
insight to cyclization of 2-alkyl aminooxazole, we
established here a one-pot facile synthesis (2–10 min) in
high yield (82–95%) of fluorophenyl aminobenzoxazoles by
the cyclodesulfurization with HgO (Scheme 7) [36].
The syntheses of the target compounds 1–5 need the key
intermediates of fluorophenyl isothiocyanates. Aryl iso-
thiocyanates, which were frequently used for the preparation
of medicine or pesticides, are usually synthesized from
arylamines through treatment with carbon disulfide, aqueous
ammonia and lead nitrate [26] or by treatment with
thiophosgene [27], the other synthetic methods were from
monoarylthioureas [27], phosphoramidates [28], arylimino-
dithiazoles [29] or amine (modified Kaluza method) [30].
However, the most of these methods are laborious and suffer
from low yields, and its very difficult for us to follow the
known synthetic methods for synthesis of fluoroaryl
isothiocyanates, as the presence of too strong electron-
withdrawing fluorine. Therefore, from the insight to
synthesis of alkylisothiocyanates, a more straightforward
and convenient synthetic route in one-step and high yield
2.2. Intermolecular hydrogen bond with F as acceptors
The X-ray structures of some compounds 1–6 were
obtained. An intermolecular hydrogen bonding (aromatic –
CH3 ꢀ ꢀ ꢀ FCsp2) between the fluorine atom on benzene ring
Scheme 5.

1612
X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
Table 1
fluorine as an acceptor, an intramolecular hydrogen bonding
(NH ꢀ ꢀ ꢀ FCsp2) between the fluorine atom on benzene ring
and hydrogen atom of an amino group on five-membered
heterocycle was also observed from its X-ray crystal
stacking spectrum, in which there are two different
conformations in one crystal unit and also fluorine group
is unlocated on 2- or 6-position (labeled as F1 and F10or F2
and F20) in each conformation. The distance of hydrogen
The substituents of compounds 1–6
R01 (R4)
R02 (R5)
Number
R1
R2
R3
R6
1a
1b
1c
1d
1e
1f
1g
1h
1i
H
F
Cl
F
F
CH2OH
CH2OH
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
F
F
F
F
F
H
F
Cl
F
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
F
CH2OH
CH2OH
H
F
Cl
H
H
H
H
H
H
F
H
H
H
F
CH2OH
CH2OH
H
H
F
CH3
CH3
F
CH3
CH3
˚
bond NH ꢀ ꢀ ꢀ F is 2.470 A, and the angle of N–H ꢀ ꢀ ꢀ F is 1158
F
H
F
CH2OH
C2H5
F
CH2OH
C2H5
(Fig. 3). Many bioorganic chemists and biochemists
believed that the formation of intermolecular F ꢀ ꢀ ꢀ H
hydrogen bonding, e.g. O–H ꢀ ꢀ ꢀ FC and N–H ꢀ ꢀ ꢀ FC hydro-
gen bonds might be important in the binding of fluorinated
substrates to enzyme active sites [37]. Nevertheless, the role
of organic fluorine atoms as hydrogen bond acceptors in at
least some systems remains controversial [37], in part
because there are few detailed studies of ‘‘unconstrained’’
intermolecular O–H ꢀ ꢀ ꢀ FC and N–H ꢀ ꢀ ꢀ FC hydrogen bonds.
So far, the reports about hydrogen bonds between fluorine
and hydrogen atom were only limited to few molecules, such
as CH4 ꢀ ꢀ ꢀ F–CH3 [38], O–H ꢀ ꢀ ꢀ F3C– [37], sp3CH ꢀ ꢀ ꢀ FCsp3
hydrogen bonding in oxirane-trifluoromethane dimer [39].
Few reports were published on CH3 or NH ꢀ ꢀ ꢀ FCsp2
hydrogen bonding, except for a relative investigation on
arene-polyfluoroarene p–p interaction for FCsp2 [40].
H
F
F
H
H
1j
F
H
H
1k
3a
3b
3c
3d
3e
3f
3g
3h
5a
5b
5c
5d
5e
5f
F
F
F
CH3
CH3
F
H
H
Cl
H
F
H
F
–
–
H
H
F
–
–
F
–
–
F
–
–
F
F
–
–
H
H
H
F
Cl
H
H
F
H
H
OH
F
–
–
–
–
–
–
F
H
F
F
F
F
F
F
F
F
H
F
F
H
H
H
H
H
Cl
Cl
H
F
F
F
H
F
F
H
F
F
H
F
F
H
5g
5h
5i
H
F
H
H
Cl
F
F
H
H
H
F
H
Cl
2.3. Fungicidal activity
2a
2b
2c
2d
2e
4a
4b
4c
4d
4e
4f
4g
4h
4i
6a
6b
6c
6d
6e
6f
F
CH2OH
CH2OH
H
F
CH2OH
CH2OH
The fungicidal activities of the above compounds against
R. solani and Pyricuraria oryzae were determined at the
concentration of 100 ppm according to the same method as
the literature [41], and the fungicidal data are listed in Table
2. Their bioactivities depend upon the number and position
of fluorine groups on the aryl rings. The fungicidal activities
of compounds in series 1, 2 and 4 are lower than those in
series 3, 5 and 6. Those in series 3 and 5 are worth studying
further. When numbers of fluorine are introduced into aryl
ring, e.g. 5a–i, the fungicidal activities increased signifi-
cantly. The fungicidal activities of several compounds in
series 5 against R. solani and P. oryzae can reach 100%. In
addition, some of series 6 exhibited definite fungicidal
activity at 1000 ppm against R. solani in vivo.
F
CH2OH
CH2OH
F
H
H
H
H
Cl
H
F
H
F
H
H
H
F
CH2OH
CH2OH
H
F
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
H
H
F
–
F
–
F
–
F
F
–
Cl
H
F
H
Cl
H
H
H
F
H
H
Cl
OH
F
–
–
–
H
F
–
b-D-Glucopyranosyl
b-D-Glucopyranosyl
b-D-Glucopyranosyl
b-D-Glucopyranosyl
b-D-Glucopyranosyl
b-D-Galactopyranosyl
b-D-Mannopyranosyl
b-D-Xylopyranosyl
b-D-Galactopyranosyl
b-D-Mannopyranosyl
b-D-Xylopyranosyl
H
H
F
F
H
F
F
F
H
H
H
H
H
H
H
Cl
F
F
F
6g
6h
6i
6j
6k
F
F
F
F
3. Experimental details
Cl
Cl
Cl
F
F
Melting points were obtained with an electrothermal
digital apparatus and are uncorrected. The infrared (IR)
spectra were recorded on a Nicolet 470 infrared Fourier
transform spectrometer using a potassium bromide pellets.
The proton nuclear magnetic resonance (1H NMR,
500 MHz) spectra were recorded on a Bruker WP-500SY
spectrometers with CD3COCD3 as the solvent and TMS as
an internal standard. High-resolution mass spectra were
obtained on MicroMass GCT CA 055 spectrometers.
Analytical thin-layer chromatography (TLC) was carried
F
and hydrogen atom of a methyl group on five-membered
heterocycle was observed on X-ray crystal stacking spect-
rum of 1k. The distance of hydrogen bond –CH3 ꢀ ꢀ ꢀ F is
˚
2.555 A, and the angle of C–H ꢀ ꢀ ꢀ F is 164.58 (Fig. 2). The
distance and angle all reach to the condition for the formation
of hydrogen bonds. When we synthesized o-fluorophenyl
thiazolidine for investigation of hydrogen bonding with

X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
1613
Table 2
Structural characterization and fungicidal activity of compound
Number
Spectrum data
Fungicidal activity
at 100 ppm (%)
R. solani
P. oryzae
1a
1H NMR (CD3COCD3, 500 MHz), d: H-20 (no signal), H-60 (no signal), 7.17 (t, J40;50 ¼ 9:0 Hz,
J50;60 ¼ 9:0 Hz, 1H, H-50), 3.71 and 3.67 (ABq, Jgem = 11.0 Hz, 4H, CH2OH), 3.32 (s, 2H,
SCH2). IR (KBr), n: 3280 (OH), 3100 (NH), 1640 (C=N), 1600, 1495 (Ph), 1190 cmꢁ1
(C–S). Anal. Calcd. for C11H12ClFN2O2S (%): C, 45.44; H, 4.13; N, 9.64. Found: C,
45.21; H, 4.28; N, 10.49
0
0
1b
1c
1H NMR (CD3COCD3, 500 MHz), d: H-60 (no signal), 7.05 (q, J30;50 ¼ 9:2 Hz, J40;50 ¼ 9:2 Hz,
J50;60 ¼ 9:2 Hz, 1H, H-50), 3.75 and 3.67 (ABq, Jgem = 11.0 Hz, 4H, CH2OH), 3.30 (s, 2H,
SCH2). IR (KBr), n: 3280 (OH), 3100 (NH), 1630 (C=N), 1505 (Ph), 1220 cmꢁ1 (C–S). Anal.
Calcd. for C11H11F3N2O2S (%): C, 45.21; H, 3.77; N, 9.59. Found: C, 45.19; H, 3.66; N, 9.67
1H NMR (CD3COCD3, 500 MHz), d: H-20 (no signal), H-60 (no signal), 7.24 (t,
0
0
7.1
15.4
J40;50 ¼ J 0 ¼ 8:0 Hz, 1H, H-50), 7.00 (d, J40;50 ¼ 8:0 Hz, 1H, H-40), 3.71 and 3.67
50;6
(ABq, Jgem = 11.0 Hz, 4H, CH2OH), 3.30 (s, 2H, SCH2). IR (KBr), n: 3280 (OH),
3100 (NH), 1640 (C=N), 1580, 1460 cmꢁ1 (Ph). MS (EI, 70 eV), m/z (%): 274 (M+ + 2)
(38), 272 (M+) (100), 243 (29), 241 (77), 213 (7), 211 (19), 129 (14), 127 (43), 31 (26). Anal. Calcd.
for C11H13ClN2O2S (%): C, 48.44; H, 4.80; N, 10.27. Found: C, 48.68; H, 4.76; N, 10.24
1H NMR (CD3COCD3, 500 MHz), d: 7.34 (br s, 0.59H, H-60), 7.05 (m, 2H, H-30
and H-50), 6.98 (m, 1H, H-40), 3.73 (s, 2H, NCH2), 3.31 (s, 2H, SCH2). IR (KBr),
n: 3100 (NH), 1630 (C=N), 1600, 1495 (Ph), 1230 cmꢁ1 (C–S). MS (EI, 70 eV),
m/z (%): 198 (40) (M+ + 2), 197 (94) (M+ + 1), 196 (100) (M+), 195 (69), 176 (38).
Anal. Calcd. for C9H9FN2S (%): C, 55.08; H, 4.62; N, 14.28. Found: C, 55.32; H, 4.53; N, 14.38
1H NMR (CD3COCD3, 500 MHz), d: H-60 (no signal), 7.05 (m, 2H, H-30 and H-50),
6.99 (m, 1H, H-40), 3.16 (s, 2H, SCH2), 1.42 (s, 6H, CH3). IR (KBr), n: 3100 (NH),
1630 (C=N), 1600, 1500 (Ph), 1250 cmꢁ1 (C–S). Anal. Calcd. for C11H13FN2S (%):
C, 58.90; H, 5.84; N, 12.49. Found: C, 58.96; H, 5.83; N, 12.57
1d
21.4
7.7
1e
1f
7.1
0
7.7
7.7
1H NMR (CD3COCD3, 500 MHz), d: H-60 (no signal), 7.05 (m, 2H, H-30 and H-50),
6.99 (m, 1H, H-40), 3.16 (s, 2H, SCH2), 1.42 (s, 6H, CH3). IR (KBr), n: 3100 (NH),
1630 (C=N), 1600, 1500 (Ph), 1250 cmꢁ1 (C–S). Anal. Calcd. for C11H13FN2S (%):
C, 58.90; H, 5.84; N, 12.49. Found: C, 58.96; H, 5.83; N, 12.57
1g
1H NMR (CD3COCD3, 500 MHz), d: 7.32 (br s, 1H, H-60), 7.06 (m, 2H, H-30
and H-50), 6.99 (m, 1H, H-40), 3.65 and 3.55 (ABq, Jgem = 10.8 Hz, 2H, CH2OH),
3.55 and 3.14 (ABq, Jgem = 11.0 Hz, 2H, SCH2), 1.76 (m, 2H, CH2), 0.99
57.1
100
(t, J = 7.4 Hz, 3H, CH3). IR (KBr), n: 3330 (OH), 3170 (NH), 1630 (C=N), 1600,
1495 (Ph), 1230 cmꢁ1 (C–S). MS (EI, 70 eV), m/z (%): 255 (M+ + 1) (32),
254 (10), 225 (12), 224 (22), 223 (100), 31 (19). Anal. Calcd. for C12H15FN2OS
(%): C, 56.67; H, 5.94; N, 11.02. Found: C, 56.84; H, 5.90; N, 10.99
1H NMR (CD3COCD3, 500 MHz), d: 7.40 (br s, 1H, H-60), 6.98 (t, J2 ;3 ¼ J3 ;4 ¼ 9:8
31.4
23.1
0
0
0
0
1h
Hz, 1H, H-30), 6.87 (t, J40;50 ¼ J 0 ¼ 8:6 Hz, 1H, H-50), 3.66 and 3.56 (ABq, Jgem
=
50;6
10.8 Hz, 2H, CH2OH), 3.34 and 3.12 (ABq, Jgem = 11.0 Hz, 2H, SCH2), 1.75 (m, 2H, CH2),
0.99 (t, J = 7.5 Hz, 3H, CH3). IR (KBr), n: 3300 (OH), 3100 (NH), 1640 (C=N),
1505 (Ph), 1240 cmꢁ1 (C–S). MS (EI, 70 eV), m/z (%): 273
(M+ + 1) (13), 272 (17), 243 (22), 242 (39), 241 (100), 225 (17), 102 (51), 101
(17), 31 (17). Anal. Calcd. for C11H14F2N2OS (%): C,
52.93; H, 5.18; N, 10.29. Found: C, 52.72; H, 5.16; N, 10.36
1i
1j
1H NMR (CD3COCD3, 500 MHz), d: 3.32 (t, 2H, J = 7.2 Hz, H-5), 3.92 (s, 2H, H-4), 7.01
(m, 2H, H-30 and H-50), 7.40 (br s, 2H, H-20 and H-60). IR (KBr), n: 3125 (NH), 2800,
1630 (C=N), 1600, 1500 (Ph), 1300, 1200, 1180, 780, 620 cmꢁ1. MS (EI, 70 eV),
m/z (%): 196 (M+) (93.04) 168 (M+ ꢁ CH2=CH2) (11.72), 149 (M+ ꢁ SCH3) (12.52),
136 (M+ ꢁ SC2H4) (100), 122 (M+ ꢁ C2H4NS) (32.36), 109 (M+ ꢁ C3H5NS)
(22.65), 95 (C6H5F) (17.34). Anal. Calcd. for C9H9 FN2S (%): C, 55.14; H,
4.63; N, 14.29. Found: C, 55.20; H, 4.73; N, 14.39
60
87.5
1H NMR (CD3COCD3, 500 MHz), d: 3.39 (t, 2H, J = 7.0 Hz, H-5), 3.74
80
85.7
(t, 2H, J = 7.0 Hz, H-4), 6.90 (br s, 1H, H-60), 7.06 (q, 1H, J4 ;5 ¼ 10:4 Hz,
0
J60;50 ¼ 10:4 Hz, J 0 ¼ 9:2 Hz, H-50). IR (KBr), n: 3150 (NH), 2850, 1650
30;5
(C=N), 1630, 1600, 1500, 1450 (Ph), 1320, 1230, 1040, 980 cmꢁ1. MS (EI, 70 eV),
m/z (%): 232 (M+) (100), 213 (M+ ꢁ F) (77.11), 185 (M+ ꢁ SCH3) (13.55), 172 (M+ ꢁ SC2H4)
(88.86), 158 (M+ ꢁ C2H4NS) (25.37), 145 (C6H5 F3N) (12.94), 61 (C2H5FS) (9.61).
Anal. Calcd. for C9H7F3N2S (%): C, 46.58;
H, 3.04; N, 12.07. Found: C, 46.42; H, 3.13; N, 11.00

1614
X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
Table 2 (Continued )
Number
Spectrum data
Fungicidal activity
at 100 ppm (%)
R. solani
P. oryzae
1k
1H NMR (CD3COCD3, 500 MHz), d: 1.43 (s, 6H, CH3), 3.22 (s, 2H, H-5), 6.81 (br s, 0.36H, H-20 and
0
0
H-60), 7.10 (q, 1H, J40;5 ¼ 8:9 Hz, J60;50 ¼ 8:9 Hz, J 0 ¼ 8:3 Hz, H-50). IR (KBr), n: 3150 (NH),
30;5
2950, 2875, 1620 (C=N), 1600, 1500 (Ph), 1300, 1260, 1230 (C–S), 1000, 820 cmꢁ1. MS (EI, 70 eV),
m/z (%): 260 (M+) (79.16), 245 (M+ ꢁ CH3) (100), 213 (M+ ꢁ SCH3) (6.7), 172 (F3C6H5N=C–NH)
(28.62), 147 (F3C6H5NH2) (12.96), 88 ((CH3)2CCH2S) (29.87), 55 (C4H7) (29.98). Anal. Calcd.
for C11H11F3N2S (%): C, 50.80; H, 4.26; N, 10.77. Found: C, 50.61; H, 4.30; N, 10.63
1H NMR (CD3COCD3, 500 MHz), d: 7.80 (br s, 1H, H-60), 7.37 (br s, 1H,
2a
2b
43.3
38.6
15.4
30.8
H-20), 7.17 (t, J40;50 ¼ 9:0 Hz, J 0 ¼ 9:0 Hz, 1H, H-50), 4.27 (s, 2H, OCH2),
50;6
3.61 (s, 4H, CH2OH). IR (KBr), n: 3250 (OH), 3108 (NH), 1660 (C=N),
1610, 1505 (Ph), 1260 cmꢁ1 (C–S). MS (EI, 70 eV), m/z (%): 276 (M+ + 2) (4),
274 (M+), 245 (34), 243 (100), 147 (4), 145 (12), 31 (21). Anal. Calcd.
for C11H12ClFN2O3 (%): C, 48.09; H, 4.37; N, 10.20. Found: C, 47.93; H, 4.52; N, 10.33
1H NMR (CD3COCD3, 500 MHz), d: 7.60 (br s, 1H, H-60), 7.07 (m, 2H, H-30
and H-50), 6.95 (m, 1H, H-40), 4.29 (s, 2H, OCH2), 3.64 (s, 4H, CH2OH). IR (KBr),
n: 3230 (OH), 3100 (NH), 1670 (C=N), 1605, 1495 (Ph), 1250 cmꢁ1 (C–S).
MS (EI, 70 eV), m/z (%): 242 (M* + 2) (73), 241 (M* + 1) (100), 240 (M*)
14), 210 (10), 209 (100), 179 (9), 110 (8), 31 (24). Anal. Calcd. for C11H13FN2O3 (%):
C, 55.00; H, 5.42; N, 11.67. Found: C, 55.06; H, 5.33; N, 11.63
2c
2d
2e
1H NMR (CD3COCD3, 500 MHz), d: H-60 (no signal), 6.98 (m, 1H, H-50), 4.52 (s,
2H, OCH2), 3.69 and 3.65 (ABq, Jgem = 11.4 Hz, 4H, CH2OH). IR (KBr), n: 3300 (OH),
1700 (C=N), 1510 (Ph), 1270 cmꢁ1 (C–S). MS (EI, 70 eV), m/z (%): 277 (M+ + 1) (14), 276 (M+)
(100), 245 (13), 195 (7), 194 (83), 176 (31), 162 (7), 148 (9), 31 (17). Anal. Calcd.
for C11H11F3N2O3 (%): C, 47.83; H, 3.99; N, 10.14. Found: C, 47.66; H, 3.71; N, 10.38
1H NMR (CD3COCD3, 500 MHz), d: 7.36 (br s, 1H, H-60), 7.03 (m, 2H, H-30 and H-50), 6.93 (m,
1H, H-40), 4.41 (t, J45 = 7.8 Hz, 2H, OCH2), 3.70 (t, J45 = 7.8 Hz, 2H, NCH2). IR (KBr),
n: 3070 (NH), 1690 (C=N), 1600, 1500 (Ph), 1230 cmꢁ1 (C–S). MS (EI, 70 eV), m/z (%): 182
(9) (M+ + 2), 181 (88) (M+ + 1), 180 (100) (M+), 161 (25), 137 (30), 122 (64), 109 (22), 95 (12), 83
(22). Anal. Calcd. for C9H9FN2O (%): C, 60.00; H, 5.03; N, 15.55. Found: C, 59.77; H, 5.02; N, 15.52
1H NMR (CD3COCD3, 500 MHz), d: 7.57 (br s, 1.46H, H-20 and H-60), 7.00 (t, J20;30 ¼ J50;60 ¼ 8:9
0
0
0
0
7.1
7.9
Hz, J30;40 ¼ J 0 ¼ 8:9 Hz, 2H, H-30 and H-50), 4.23 (s, 2H, OCH2), 3.62 and 3.64 (ABq, Jgem
40;5
= 11.0 Hz, 4H, CH2OH). MS (EI, 70 eV), m/z (%): 242 (M* + 2) (86), 241 (M* + 1) (100),
240 (M*) (26), 210 (22), 209 (63), 179 (22), 110 (19), 31 (29). IR (KBr), n: 3205 (OH),
3100 (NH), 1655 (C=N), 1600, 1510 (Ph), 1220 cmꢁ1 (C–S). Anal. Calcd. for C11H13FN2O3
(%): C, 55.00; H, 5.42; N, 11.67. Found: C, 55.16; H, 5.37; N, 11.58
2f
1H NMR (CD3COCD3, 500 MHz), d: 1.39 (s, 6H, CH3) 3.18 (s, 2H, H-5), 7.00 (t, 2H, J20;30 ¼ J50;60 ¼ 8:3
0
7.7
Hz, J40;30 ¼ J 0 ¼ 8:8 Hz, H-30 and H-50), 7.36 (br s, 1.2H, H-20 and H-60). IR (KBr), n: 3100 (NH),
40;5
2950, 2825 (C–H), 1630 (C=N), 1590, 1500 (Ph), 1320, 1210 (C–S), 1190, 1170, 850, 760, 650 cmꢁ1
.
MS (EI, 70 eV), m/z (%): 225 (M+ + 1) (23.84), 224 (M+) (45.53), 209 (M+ ꢁ CH3) (100), 137 (FC6H5N
=C–NH2) (11.80), 136 (FC6H5N=CNH) (27.87), 88 ((CH3)2CCH2S) (12.72). Anal. Calcd. for
C11H13FN2S (%): C, 53.60; H, 5.85; N, 12.50. Found: C, 53.68; H, 5.90; N, 12.61
3a
3b
3c
1H NMR (D2O, 500 MHz), d: 7.05–7.11 (m, 4H, ArH), 4.72 (m, 1H, H-5), 3.48–3.91 [m, 7H, CH
(OH)CH(OH)CH(OH)CH2OH and NCH2], 2.91 (s, 3H, CH3N). IR (KBr), n: 3370 (OH), 1670 cmꢁ1
(C=N). MS (EI, 70 eV), m/z (%): 314 (M+) (1), 137 (5), 111 (6), 44 (100), 31 (28), 15 (10). Anal. Calcd.
for C14H19FN2O5 (%): C, 53.50; H, 6.09; N, 8.91. Found: C, 53.72; H, 6.14; N, 8.87
1H NMR (D2O, 500 MHz), d: 7.01 (m, 4H, ArH), 4.70 (m, 1H, H-5), 3.40–3.90 [m, 7H, CH
(OH)CH(OH)CH(OH)CH2OH and NCH2], 2.87 (s, 3H, CH3N). IR (KBr), n: 3300 (OH), 1665 cmꢁ1
(C=N). MS (EI, 70 eV), m/z (%): 314 (M+) (1), 202 (6), 137 (10), 111 (6), 44 (100), 31 (22), 15 (23).
Anal. Calcd. for C14H19FN2O5 (%): C, 53.50; H, 6.09; N, 8.91. Found: C, 53.84; H, 6.07; N, 8.85
1H NMR (D2O, 500 MHz), d: 7.16 (dd, J20;40 ¼ 6:7 Hz, J20;60 ¼ 2:6 Hz, 1H, H-20), 7.10 (t, J40;60 ¼ 9:0 Hz,
J50;60 ¼ 9:0 Hz, 1H, H-60), 6.93 (m, 1H, H-50), 4.74 (m, 1H, H-5), 3.51–3.93 [m, 7H,
CH(OH)CH(OH)CH(OH)CH2OH and NCH2], 2.91 (s, 3H, CH3N). IR (KBr), n: 3400 (OH), 1680 cmꢁ1
(C=N). MS (EI, 70 eV), m/z (%): 350 (M+ + 2) (2), 348 (M+) (6), 179 (9), 145 (12), 117 (11), 44 (100),
31 (13), 15 (23). Anal. Calcd. for C14H18ClFN2O5 (%): C, 48.22; H, 5.20; N, 8.03. Found: C,
48.51; H, 5.30; N, 8.16
38.6
64.3
64.3
30.8
69.2
38.5
3d
1H NMR (D2O, 500 MHz), d: 6.96 (td, J20;60 ¼ 6:3 Hz, J40;60 ¼ 9:1 Hz, J50;60 ¼ 9:1 Hz, 1H, H-60),
0
0
6.84 (t, J2 ;3 ¼ 10:7 Hz, J3 ;4 ¼ 10:7 Hz, 1H, H-30), 6.76 (t, J4 ;5 ¼ 9:1 Hz, J5 ;6 ¼ 9:1 Hz, 1H, H-50), 4.62
(m, 1H, H-5), 3.37–3.81 [m, 7H, CH(OH)CH(OH)CH(OH)CH2OH and NCH2], 2.91 (s, 3H, CH3N). IR
(KBr), n: 3400 (OH), 1680 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 332 (M+) (2), 202 (48), 201 (23), 200
(38), 199 (28), 198 (18), 144 (100), 31 (27), 15 (12). Anal. Calcd. for C14H18F2N2O5 (%): C, 50.60;
H, 5.46; N, 8.43. Found: C, 50.54; H, 5.42; N, 8.37
0
0
0
0
0
0
0
0

X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
1615
Table 2 (Continued)
Number
Spectrum data
Fungicidal activity
at 100 ppm (%)
R. solani
P. oryzae
3e
1H NMR (D2O, 500 MHz), d: 6.90 (m, 1H, H-60), 6.79 (m, 1H, H-50), 4.70 (m, 1H, H-5), 3.44–
3.86 [m, 7H, CH(OH)CH(OH)CH(OH)CH2OH and NCH2], 2.87 (s, 3H, CH3N). IR (KBr), n: 3400
(OH), 1670 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 350 (M+) (100), 117 (14), 44 (25), 31 (5), 15 (2).
Anal. Calcd. for C14H17F3N2O5 (%): C, 48.00; H, 4.89; N, 8.00. Found: C, 47.62; H, 4.83; N, 8.04
1H NMR (D2O, 500 MHz), d: 7.19 (t, J40;50 ¼ 8:0 Hz, J50;60 ¼ 8:0 Hz, 1H, H-50), 7.05 (s, 1H, H-20),
7.01 (d, J50;60 ¼ 8:0 Hz, 1H, H-60), 6.91 (d, J40;50 ¼ 8:0 Hz, 1H, H-40), 4.70 (m, 1H, H-5), 3.41–3.88
[m, 7H, CH(OH)CH(OH)CH(OH)CH2OH and NCH2], 2.84 (s, 3H, CH3N). IR (KBr), n: 3390 (OH),
1660 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 332 (M+ + 2) (38), 330 (M+) (100), 177 (29), 116 (22),
44 (64). Anal. Calcd. for C14H19ClN2O5 (%): C, 50.84; H, 5.79; N, 8.47. Found: C, 50.62; H, 5.71; N, 8.51
1H NMR (D2O, 500 MHz), d: 7.28 (t, J20;30 ¼ 7:8 Hz, J30;40 ¼ 7:8 Hz, J40;50 ¼ 7:8 Hz, J50;60 ¼ 7:8
Hz, 2H, H-30 and H-50), 7.01–7.06 (m, 3H, H-20, H-60 and H-40), 4.70 (m, 1H, H-5), 3.42–3.90 [m, 7H,
CH(OH)CH(OH)CH(OH)CH2OH and NCH2], 2.88 (s, 3H, CH3N). IR (KBr), n: 3300 (OH), 1650 cmꢁ1
(C=N). MS (EI, 70 eV), m/z (%): 297 (M+ + 1) (28), 296 (M+) (53), 116 (46), 93 (48), 77 (20), 43 (100), 31
(43), 15 (12). Anal. Calcd. for C14H20N2O5 (%): C, 56.75; H, 6.80; N, 9.45. Found: C, 56.32; H, 6.84; N, 9.37
1H NMR (D2O, 500 MHz), d: 6.92 (d, J20;30 ¼ J50;60 ¼ 8:7 Hz, 2H, H-20 and H-60), 6.77 (d,
73.7
38.5
3f
65.8
7.9
38.5
7.7
3g
3h
89.5
100
J20;30 ¼ J 0 ¼ 8:7 Hz, 2H, H-30 and H-50), 4.70 (m, 1H, H-5), 3.40–3.90 [m, 7H, CH(OH)
50;6
CH(OH)CH(OH)CH2OH and NCH2], 2.86 (s, 3H, CH3N). IR (KBr), n: 3400 (OH), 1660 cmꢁ1
(C=N). MS (EI, 70 eV), m/z (%): 312 (M+) (0.4), 135 (11), 109 (8), 43 (100), 31 (9), 15 (3). Anal.
Calcd. for C14H20N2O6 (%): C, 53.84; H, 6.45; N, 8.97. Found: C, 53.71; H, 6.52; N, 9.03
1H NMR (CD3COCD3, 500 MHz), d: 8.45 (m, 1H, H-60), 7.14–7.30 (m, 5H, H-30, H-40, H-50,
H-6 and H-7). IR (KBr), n: 3410 (NH), 1660 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 264 (M+)
(100), 245 (73), 122 (22), 96 (25), 95 (15), 83 (16), 75 (34). Anal. Calcd. for C13H7F3N2O: C,
59.10; H, 2.67; N, 10.60. Found: C, 59.33; H, 2.73; N, 10.79
4a
4b
50.0
14.3
7.7
0
1H NMR (CD3COCD3, 500 MHz), d: 7.87 (dd, J20;40 ¼ 5:9 Hz, J40;60 ¼ 5:9 Hz, J20;30 ¼ 9:2 Hz,
J50;60 ¼ 9:2 Hz, 2H, H-20 and H-60), 7.19 (t, J20;30 ¼ 9:2 Hz, J
30;40 ¼ 9:2 Hz, J40;50 ¼ 9:2 Hz,
J50;60 ¼ 9:2 Hz, 2H, H-30 and H-50), 7.20–7.24 (m, 2H, H-6 and H-7). IR (KBr), n: 3420 (NH),
1700 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 264 (M+) (100), 245 (3), 122 (12), 96 (18), 95 (13),
83 (7), 75 (11). Anal. Calcd. for C13H7F3N2O: C, 59.10; H, 2.67; N, 10.60. Found: C, 59.25; H, 2.68; N, 10.49
1H NMR (CD3COCD3, 500 MHz), d: 8.15 (dd, J20;40 ¼ 6:5 Hz, J20;60 ¼ 2:7 Hz, 1H, H-20), 7.70
4c
17.0
0
40;60 ¼ 3:2 Hz, J506
(ddd, J20;60 ¼ 2:8 Hz, J
0 ¼ 9:0 Hz, 1H, H-60), 7.35 (t, J40;50 ¼ 9:0 Hz,
J50;60 ¼ 9:0 Hz, 1H, H-50), 7.15–7.30 (m, 2H, H-6 and H-7). IR (KBr), n: 3420 (NH), 1700 cmꢁ1
(C=N). MS (EI, 70 eV), m/z (%): 301 (M+ + 2) (6), 299 (M+) (33), 298 (22), 297 (100),
296 (15), 262 (8), 156 (10), 130 (13), 129 (10), 109 (7). Anal. Calcd. for C13H6ClF3N2O:
C, 52.28; H, 2.02; N, 9.38. Found: C, 51.73; H, 2.21; N, 9.32
1H NMR (CD3COCD3, 500 MHz), d: 8.29 (td, J2 ;6 ¼ 5:9 Hz, J4 ;6 ¼ 9:2 Hz, J5 ;6 ¼ 9:2 Hz,
32.8
25.7
31.6
7.7
30.8
76.9
0
0
0
0
0
0
4d
4e
4f
1H, H-60), 7.15 (t, J20;30 ¼ 9:2 Hz, J 0 ¼ 9:2 Hz, 1H, H-30), 7.17–7.22 (m, 3H, H-50, H-6, H-7).
30;4
IR (KBr), n: 3420 (NH), 1700 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 282 (M+) (100), 263 (100),
140 (43), 114 (53), 101 (24). Anal. Calcd. for C13H6F4N2O: C, 55.33; H, 2.14; N, 9.93.
Found: C, 55.38; H, 2.15; N, 9.93
1H NMR (CD3COCD3, 500 MHz), d: 8.20 (m, 1H, H-60), 7.30 (qd, J30;50 ¼ 9:1 Hz, J40;50 ¼ 9:1 Hz,
J50;60 ¼ 9:1 Hz, J 0 ¼ 2:1 Hz, 1H, H-50), 7.20–7.26 (m, 2H, H-6, H-7). IR (KBr), n: 3430 (NH),
20;5
1680 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 300 (M+) (100), 282 (14), 281 (68), 158 (45), 132 (51),
131 (21), 119 (35), 115 (32), 88 (65), 81 (63), 64 (63). Anal. Calcd. for C13H5F5N2O: C, 52.01;
H, 1.68; N, 9.33. Found: C, 52.18; H, 1.67; N, 9.31
1H NMR (CD3COCD3, 500 MHz), d: 8.40 (dd, J40;60 ¼ 1:5 Hz, J50;60 ¼ 8:0 Hz, 1H, H-60),
7.52 (dd, J30;50 ¼ 1:5 Hz, J 0 ¼ 8:0 Hz, 1H, H-30), 7.45 (td, J30;50 ¼ 1:4 Hz, J
30;4
40;50 ¼ 8:0 Hz,
0 ¼ 8:0 Hz, 1H, H-40),
J50;60 ¼ 8:0 Hz, 1H, H-50), 7.18 (td, J40;60 ¼ 1:5 Hz, J
30;40 ¼ 8:0 Hz, J40;5
7.21–7.25 (m, 2H, H-6, H-7). IR (KBr), n: 3400 (NH), 1600 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%):
282 (M+ + 2) (33), 280 (M+) (100), 246 (16), 245 (100), 203 (18), 202 (17), 100 (17), 75 (36), 64 (26).
Anal. Calcd. for C13H7ClF2N2O: C, 55.63; H, 2.51; N, 9.88. Found: C, 55.52; H, 2.50; N, 9.96
1H NMR (CD3COCD3, 500 MHz), d: 8.07 (t, J20;60 ¼ 2:0 Hz, J20;40 ¼ 2:0 Hz, 1H, H-20),
4g
31.6
23.1
7.60 (ddd, J20;60 ¼ 2:0 Hz, J
0 ¼ 8:1 Hz, 1H, H-60), 7.54 (t, J40;50 ¼ 8:1 Hz,
40;60 ¼ 0:8 Hz, J50;6
J50;60 ¼ 8:1 Hz, 1H, H-50), 7.17 (ddd, J40;60 ¼ 0:8 Hz, J
0 ¼ 8:1 Hz, 1H, H-40),
20;40 ¼ 2:0 Hz, J40;5
7.20–7.30 (m, 2H, H-6, H-7). IR (KBr), n: 3420 (NH), 1700 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%):
282 (M+ + 2) (33), 280 (M+) (100), 279 (28), 245 (13), 203 (8), 202 (7), 100 (13), 75 (35), 64 (20).
Anal. Calcd. for C13H7ClF2N2O: C, 55.63; H, 2.51; N, 9.88. Found: C, 55.48; H, 2.53; N, 10.00

1616
X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
Table 2 (Continued )
Number
Spectrum data
Fungicidal activity
at 100 ppm (%)
R. solani
P. oryzae
4h
1H NMR (CD3COCD3, 500 MHz), d: 8.49 (t, J20;60 ¼ 8:9 Hz, J50;60 ¼ 8:9 Hz, 1H, H-60),
7.38 (m, 2H, H-30 and H-50), 7.14–7.25 (m, 2H, H-6 and H-7). IR (KBr), n: 3160 (NH),
1700 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 301 (M+ + 2) (16), 299 (M+) (50), 298 (100),
279 (16), 263 (12), 156 (7), 130 (6). Anal. Calcd. for C13H6ClF3N2O: C, 52.28; H, 2.02;
N, 9.38. Found: C, 52.03; H, 2.15; N, 9.30
31.6
23.1
4i
1H NMR (CD3COCD3, 500 MHz), d: 7.60 (d, J20;30 ¼ 8:9 Hz, J50;60 ¼ 8:9 Hz, 2H, H-60), 6.89
52.9
6.7
(d, J20;30 ¼ 8:9 Hz, J 0 ¼ 8:9 Hz, 2H, H-30 and H-50), 7.20–7.30 (m, 2H, H-6 and H-7). IR
50;6
(KBr), n: 3420 (NH), 3290 (OH), 1700 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 262 (M+) (100).
Anal. Calcd. for C13H8F2N2O2: C, 59.55; H, 3.08; N, 10.68. Found: C, 59.64; H, 3.06; N, 10.52
1H NMR (D2O, 500 MHz), d: 6.73–7.80 (m, 5H, ArH), 2.50 (s, 3H, SCH3). IR (KBr),
n: 3120 (NH), 1610 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 332 (M+) (33), 285 (51),
284 (100), 204 (100), 146 (23), 128 (28), 127 (62). Anal. Calcd. for C14H9F5N2S:
C, 50.60; H, 2.73; N, 8.43. Found: C, 50.42; H, 2.71; N, 8.46
5a
5b
5c
100
100
100
100
1H NMR (D2O, 500 MHz), d: 7.51 (m, 1H, H-60), 7.05–7.24 (m, 2H, H-5 and H-50), 6.75
(m, 1H, H-6), 2.55 (s, 3H, SCH3). IR (KBr), n: 3160 (NH), 1570 cmꢁ1 (C=N). MS (EI, 70 eV),
m/z (%): 350 (M+) (10), 303 (20), 302 (39), 204 (100), 189 (44), 146 (56). Anal. Calcd.
for C14H8F6N2S: C, 48.01; H, 2.30; N, 8.00. Found: C, 47.94; H, 2.46; N, 7.87
1H NMR (D2O, 500 MHz), d: 7.82 (m, 1H, H-60), 7.41 (m, 1H, H-20), 7.22 (q, J30;50 ¼ 9:3 Hz,
92.1
77.6
J40;50 ¼ 9:3 Hz, J 0 ¼ 9:3 Hz, 1H, H-50), 7.10 (m, 1H, H-5), 6.80 (m, 1H, H-6), 2.50 (s, 3H, SCH3).
50;6
IR (KBr), n: 3170 (NH), 1590 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 332 (M+) (8), 285 (21), 284 (100),
204 (16), 145 (13), 127 (19). Anal. Calcd. for C14H9F5N2S: C, 50.60; H, 2.73; N, 8.43. Found:
C, 50.71; H, 2.72; N, 8.45
5d
5e
5f
1H NMR (D2O, 500 MHz), d: 6.99–7.92 (m, 6H, ArH), 2.51 (s, 3H, SCH3). IR (KBr),
n: 3210 (NH), 1560 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 314 (M+) (7), 267 (17),
266 (32), 186 (100), 171 (100), 128 (62). Anal. Calcd. for C14H10F4N2S: C, 53.50;
H, 3.21; N, 8.91. Found: C, 53.47; H, 3.40; N, 8.87
1H NMR (D2O, 500 MHz), d: 7.91 (m, 1H, H-60), 7.40 (m, 1H, H-20), 6.93–7.01
(m, 3H, H-3, H-5 and H-6), 2.49 (s, 3H, SCH3). IR (KBr), n: 3160 (NH), 1580 cmꢁ1 (C=N).
MS (EI, 70 eV), m/z (%): 314 (M+) (10), 267 (78), 266 (100), 186 (23), 171 (15), 127 (35),
95 (26). Anal. Calcd. for C14H10F4N2S: C, 53.50; H, 3.21; N, 8.91. Found: C, 53.68; H, 3.21; N, 8.90
1H NMR (D2O, 500 MHz), d: 6.85–7.95 (m, 8H, ArH), 2.50 (s, 3H, SCH3).
IR (KBr), n: 3210 (NH), 1590 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%):
89.5
84.2
81.6
78.9
100
100
100
100
278 (M+) (14), 231 (38), 230 (29), 168 (100), 153 (53), 110 (38), 95 (26). Anal.
Calcd. for C14H12F2N2S: C, 60.42; H, 4.35; N, 10.07. Found: C, 60.47; H, 4.27; N, 10.08
1H NMR (D2O, 500 MHz), d: 7.71 (m, 2H, H-20 and H-60), 7.05 (t,
5g
J2;3 ¼ J20;30 ¼ J ¼ J 0 ¼ 8:8 Hz, H-3, H-5, H-30 and H-50), 6.90 (m, 2H, H-20
50;6
5;6
and H-60), 2.42 (s, 3H, SCH3). IR (KBr), n: 3150 (NH), 1580 cmꢁ1 (C=N). MS (EI, 70 eV),
m/z (%): 278 (M+) (63), 231 (58), 230 (82), 168 (100), 153 (48), 110 (79), 95 (02). Anal.
Calcd. for C14H12F2N2S: C, 60.42; H, 4.35; N, 10.07. Found: C, 60.54; H, 4.36; N, 10.05
1H NMR (D2O, 500 MHz), d: 6.91–7.92 (m, 6H, ArH), 2.43 (s, 3H, SCH3). IR (KBr),
n: 3200 (NH), 1540 cmꢁ1 (C=N). MS (EI, 70 eV), m/z (%): 346 (M+) (6), 302 (13),
300 (67), 298 (100), 204 (12), 202 (35). Anal. Calcd. for C14H10Cl2F2N2S: C, 48.43;
H, 2.90; N, 8.07. Found: C, 48.58; H, 2.91; N, 8.10
5h
5i
65.8
38.3
100
1H NMR (D2O, 500 MHz), d: 7.94 (m, 1H, H-20), 7.58 (m, 1H, H-60), 7.19 (t,
92.3
J4;5 ¼ J4 ;5 ¼ 9:0 Hz, J5;6 ¼ J5 ;6 ¼ 9:0 Hz, 2H-5 and H-50), 7.01 (m, 1H, H-2),
6.85 (m, 1H, H-6), 2.43 (s, 3H, SCH3). IR (KBr), n: 3180 (NH), 1570 cmꢁ1 (C=N).
MS (EI, 70 eV), m/z (%): 346 (M+) (2), 302 (12), 300 (66), 298 (100), 143 (15),
129 (13). Anal. Calcd. for C14H10Cl2F2N2S: C, 48.43; H, 2.90; N, 8.07. Found:
C, 48.62; H, 2.88; N, 8.09
0
0
0
0
6a
1H NMR (CD3COCD3, 500 MHz), d: 7.20 (td, J40;60 ¼ 9:1 Hz, J50;60 ¼ 9:1 Hz, J20;60 ¼ 5:6 Hz,
0 (in vivo)
-
1H, H-60), 6.96 (ddd, J20;30 ¼ 8:7 Hz, J
0 ¼ 2:8 Hz, 1H, H-30), 6.85
30;40 ¼ 11:2 Hz, J30;5
30;50 ¼ 2:8 Hz, J50;6
(tdd, J20;50 ¼ 1:5 Hz, J
0 ¼ 9:1 Hz, 1H, H-50), 4.50 (d, J1,2 = 8.0 Hz,
1H, H-1), 3.76 (dd, J5,6 = 2.2 Hz, Jgem = 12.3 Hz, 1H, H-6a), 3.58 (dd, J5,6 = 5.5 Hz,
Jgem = 12.3 Hz, 1H, H-6b), 3.41 (m, 2H, H-2 and H-3), 3.20 (m, 2H, H-4 and H-5). IR (KBr),
n: 3310 (NH), 3250 (OH), 1600 and 1570 cmꢁ1 (Ph). MS (EI, 70 eV), m/z (%): 291 (M+) (2),
129 (100), 109 (24), 101 (73), 82 (47). Anal. Calcd. for C12H15F2NO5ꢀH2O: C, 46.60;
H, 5.54; N, 4.53. Found: C, 46.54; H, 5.56; N, 4.55

X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
1617
Table 2 (Continued)
Number
Spectrum data
Fungicidal activity
at 100 ppm (%)
R. solani
P. oryzae
–
6b
1H NMR (CD3COCD3, 500 MHz), d: 7.02 (q, J30;50 ¼ 9:1 Hz, J40;50 ¼ 9:1 Hz, J50;60 ¼ 9:1 Hz,
90
1H, H-50), 6.65 (ddd, J20;30 ¼ 12:9 Hz, J
0 ¼ 2:7 Hz, 1H, H-20), 6.49
20;40 ¼ 6:9 Hz, J20;6
(d, J50;60 ¼ 9:0 Hz, 1H, H-60), 4.57 (d, J1,2 = 8.8 Hz, 1H, H-1), 3.78 (dd, J5,6 = 2.2 Hz, Jgem
12.3 Hz, 1H, H-6a), 3.62 (dd, J5,6 = 5.5 Hz, Jgem = 12.3 Hz, 1H, H-6b), 3.45 (m, 2H,
H-2 and H-3), 3.35 (m, 2H, H-4 and H-5). IR (KBr), n: 3350 (NH), 3260 (OH), 1600
cmꢁ1 (Ph). MS (EI, 70 eV), m/z (%): 291 (M+) (5), 142 (100), 129 (42), 113 (40).
=
Anal. Calcd. for C12H15F2NO5ꢀH2O: C, 46.60; H, 5.54; N, 4.53. Found: C, 46.58; H, 5.52; N, 4.56
6c
1H NMR (CD3COCD3, 500 MHz), d: 6.92 (t, J20;30 ¼ 8:9 Hz, J20;40 ¼ 8:9 Hz, J4060 ¼ 8:9 Hz,
0
–
J50;60 ¼ 8:9 Hz, 2H, H-30 and H-50), 6.71 (q, J20;30 ¼ 8:9 Hz, J
20;40 ¼ 4:5 Hz, J4060 ¼ 4:5 Hz,
J50;60 ¼ 8:9 Hz, 2H, H-20 and H-60), 4.60 (d, J1,2 = 8.8 Hz, 1H, H-1), 3.79 (dd, J5,6 = 2.0 Hz,
Jgem = 12.3 Hz, 1H, H-6a), 3.58 (dd, J5,6 =5.6 Hz, Jgem = 12.3 Hz, 1H, H-6b), 3.41 (m, 2H,
H-2 and H-3), 3.20 (m, 2H, H-4 and H-5). IR (KBr), n: 3320 (NH), 3260 (OH), 1510 cmꢁ1 (Ph).
EIMS: m/z (%): 273 (M+) (8), 124 (100), 111 (71), 95 (48), 75 (24). Anal. Calcd. for
C, 49.48; H, 6.23; N, 4.81. Found: C, 49.32; H, 6.24; N, 4.81
6d
6e
6f
1H NMR (CD3COCD3, 500 MHz), d: 6.88 (qd, J30;50 ¼ 9:0 Hz, J40;50 ¼ 9:0 Hz, J50;60 ¼ 9:0 Hz, J20;50 ¼ 2:1 Hz,
0
70
0
–
–
–
–
1H, H-50), 6.64 (tq, J20;60 ¼ 4:7 Hz, J
0 ¼ 9:0 Hz, 1H, H-60), 4.60
30;60 ¼ 2:2 Hz, J4060 ¼ 9:0 Hz, J50;6
(d, J1,2 = 8.7 Hz, 1H, H-1), 3.79 (dd, J5,6 = 2.1 Hz, Jgem = 12.4 Hz, 1H, H-6a), 3.58 (dd, J5,6 = 5.5 Hz,
Jgem = 12.4 Hz, 1H, H-6b), 3.45 (m, 2H, H-2 and H-3), 3.38 (m, 2H, H-4 and H-5).
IR (KBr), n: 3310 (NH), 3260 (OH), 1590 and 1570 (Ph) mꢁ1. MS (EI, 70 eV), m/z (%): 309 (M+) (3), 147 (100),
119 (47). Anal. Calcd. for C12H14F3NO5ꢀH2O: C, 44.04; H, 4.93; N, 4.28. Found: C, 43.90; H, 4.90; N, 4.28
1H NMR (CD3COCD3, 500 MHz), d: 7.05 (t, J40;50 ¼ 8:9 Hz, J50;60 ¼ 8:9 Hz, 1H, H-50), 6.85 (s, 1H, H-20),
6.67 (dd, J40;60 ¼ 6:1 Hz, J 0 ¼ 8:9 Hz, 1H, H-60), 4.58 (d, J1,2 = 8.2 Hz, 1H, H-1), 3.76 (dd,
50;6
J5,6 = 2.2 Hz, Jgem = 12.3 Hz, 1H, H-6a), 3.62 (dd, J5,6 = 5.5 Hz, Jgem = 12.3 Hz, 1H, H-6b), 3.45
(m, 2H, H-2 and H-3), 3.35 (m, 2H, H-4 and H-5). IR (KBr), n: 3310 (NH), 3250 (OH), 1600 and
1500 cmꢁ1 (Ph). MS (EI, 70 eV), m/z (%): 309 (M+ + 2) (33), 307 (M+) (100), 290 (5), 288 (15), 160 (8),
158 (24). Anal. Calcd. for C12H15ClFNO5ꢀH2O: C, 44.25; H, 5.26; N, 4.30. Found: C, 44.18; H, 5.24; N, 4.32
1H NMR (CD3COCD3, 500 MHz), d: 7.10 (q, J30;50 ¼ 9:2 Hz, J40;50 ¼ 9:2 Hz, J50;60 ¼ 9:2 Hz,
1H, H-50), 6.76 (ddd, J20;30 ¼ 12:8 Hz, J
0 ¼ 2:5 Hz, 1H, H-20), 6.61 (m, 1H, H-60),
20;40 ¼ 6:8 Hz, J20;6
4.63 (d, J1,2 = 8.8 Hz, 1H, H-1), 4.00 (d, J5,6 = 2.0 Hz, 1H, H-6a), 3.80 (t, J3,4 = 6.1 Hz, J4,5 = 6.1 Hz, 1H,
H-4), 3.63–3.75 (m, 4H, H-2, H-3, H-5 and H-6b). IR (KBr), n: 3340 (NH), 3250 (OH), 1595 cmꢁ1 (Ph).
MS (EI, 70 eV), m/z (%): 291 (M+) (5), 143 (19), 142 (100), 129 (30), 115 (23), 113 (25). Anal. Calcd.
for C12H15F2NO5: C, 49.49; H, 5.19; N, 4.86. Found: C, 48.91; H, 5.12; N, 4.74
6g
1H NMR (CD3COCD3, 500 MHz), d: 7.11 (q, J30;50 ¼ 9:0 Hz, J40;50 ¼ 9:0 Hz, J50;60 ¼ 9:0 Hz,
0
1H, H-50), 6.78 (ddd, J20;30 ¼ 12:9 Hz, J
0 ¼ 2:7 Hz, 1H, H-20), 6.61
20;40 ¼ 6:8 Hz, J20;6
(m, 1H, H-60), 4.93 (d, J1,2 = 2.1 Hz, 1H, H-1), 4.03 (d, J5,6 = 2.7 Hz, 1H, H-6a), 3.88
(dd, J5,6 = 2.2 Hz, Jgem = 12.2 Hz, 1H, H-6b), 3.70–3.74 (m, 2H, H-2 and H-3), 3.63
(t, J3,4 = 9.7 Hz, J4,5 = 9.7 Hz, 1H, H-4), 3.49 (m, 1H, H-5). IR (KBr), n: 3345 (NH), 3270 (OH),
1602 cmꢁ1 (Ph). MS (EI, 70 eV), m/z (%): 291 (M+) (2), 143 (11), 142 (100), 129 (43), 114 (26),
113 (24). Anal. Calcd. for C12H15F2NO5: C, 49.11; H, 5.09; N, 4.78. Found: C, 48.91; H, 5.12; N, 4.74
1H NMR (CD3COCD3, 500 MHz), d: 6.94 (q, J30;50 ¼ 9:1 Hz, J40;50 ¼ 9:1 Hz, J50;60 ¼ 9:1 Hz, 1H, H-50),
6h
0
0
0
–
–
–
6.57 (ddd, J2 ;3 ¼ 12:9 Hz, J2 ;4 ¼ 6:9 Hz, J2 ;6 ¼ 2:7 Hz, 1H, H-20), 6.41 (m, 1H, H-60), 4.45
(d, J1,2 = 8.7 Hz, 1H, H-1), 3.72 (dd, J4,5 = 5.38 Hz, Jgem = 11.4 Hz, 1H, H-5a), 3.45 (m, 1H, H-4),
3.34 (t, J2,3 = 9.1 Hz, J3,4 = 9.1 Hz, 1H, H-3), 3.20–3.26 (m, 2H, H-2 and H-5b). IR (KBr), n: 3320 (NH),
3270 (OH), 1580 cmꢁ1 (Ph). MS (EI, 70 eV), m/z (%): 261 (M+) (4), 260 (M+ ꢁ 1) (26), 130 (13),
129 (100), 114 (18), 113 (23). Anal. Calcd. for C11H13F2NO4: C, 50.58; H, 5.02; N, 5.36.
Found: C, 50.32; H, 5.03; N, 5.38
0
0
0
0
0
0
6i
1H NMR (CD3COCD3, 500 MHz), d: 7.11 (t, J40;50 ¼ 9:1 Hz, J50;60 ¼ 9:1 Hz, 1H, H-50), 6.97 (dd,
J20;60 ¼ 2:7 Hz, J 0 ¼ 6:2 Hz, 1H, H-20), 6.77 (ddd, J20;60 ¼ 2:7 Hz, J
20;4
4060 ¼ 5:4 Hz, J50;60 ¼ 9:1
Hz, 1H, H-60), 4.62 (d, J1,2 = 8.7 Hz, 1H, H-1), 4.00 (d, J5,6 = 2.2 Hz, 1H, H-6a), 3.80 (t, J3,4 = 6.2 Hz,
J4,5 = 6.2 Hz, 1H, H-4), 3.72–3.77 (m, 3H, H-3, H-5 and H-6b), 3.64 (t, J1,2 = 8.7 Hz, J2,3 = 8.7 Hz, 1H, H-2).
IR (KBr), n: 3340 (NH), 3260 (OH), 1595 and 1500 cmꢁ1 (Ph). MS (EI, 70 eV), m/z (%): 309 (M+ + 2) (3),
307 (M+) (5), 160 (35), 158 (100), 147 (9), 145 (27), 131 (7), 129 (15). Anal. Calcd. for C12H15ClFNO5:
C, 46.84; H, 4.91; N, 4.55. Found: C, 46.47; H, 4.84; N, 4.49
6j
1H NMR (CD3COCD3, 500 MHz), d: 7.02 (t, J40;50 ¼ 8:9 Hz, J50;60 ¼ 9:1 Hz, 1H, H-50), 6.98
(dd, J20;60 ¼ 2:6 Hz, J 0 ¼ 6:2 Hz, 1H, H-20), 6.79 (m, 1H, H-60), 4.94 (d, J1,2 = 2.1 Hz, 1H, H-1),
20;4
4.03 (d, J5,6 = 3.1 Hz, 1H, H-6a), 3.89
(dd, J5,6 = 1.7 Hz, Jgem = 12.3 Hz, 1H, H-6b), 3.69–3.78 (m, 2H, H-2 and H-3), 3.63 (t, J3,4 = 9.7 Hz,
J4,5 = 9.7 Hz, 1H, H-4), 3.48 (m, 1H, H-5). IR (KBr), n: 3320 (NH), 3250 (OH), 1600 and 1500 cmꢁ1
(Ph). MS (EI, 70 eV), m/z (%): 309 (M+ + 2) (9), 307 (M+) (23), 160 (32), 158 (100), 147 (17), 145 (53), 131
(9), 129 (20). Anal. Calcd. for C12H15ClFNO5: C, 46.84; H, 4.91; N, 4.55. Found: C, 46.75; H, 4.93; N, 4.50

1618
X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
Table 2 (Continued )
Number
Spectrum data
Fungicidal activity
at 100 ppm (%)
R. solani
P. oryzae
6k
1H NMR (CD3COCD3, 500 MHz), d: 7.12 (t, J40;50 ¼ 9:1 Hz, J50;60 ¼ 9:1 Hz, 1H, H-50), 6.95 (dd, J20;60 ¼ 2:5 Hz,
J20;40 ¼ 6:1 Hz, 1H, H-20), 6.76 (m, 1H, H-60), 4.63 (d, J1,2 = 8.7 Hz, 1H, H-1), 3.72 (dd, J4,5 = 5.3 Hz,
Jgem = 11.4 Hz, 1H, H-5a), 3.63 (m, 1H, H-4), 3.52 (t, J1,2 = 9.1 Hz, J2,3 = 9.1 Hz, 1H, H-3), 3.38–3.44
(m, 2H, H-2 and H-5b). IR (KBr), n: 3320 (NH), 3260 (OH), 1585 and 1500 cmꢁ1 (Ph). MS (EI, 70 eV),
m/z (%): 279 (M+ + 2) (3), 278 (M+ + 1) (10), 277 (M+) (8), 276 (M+ ꢁ 1) (28), 160 (31), 158 (100), 147 (22),
145 (68), 131 (9), 129 (21). Anal. Calcd. for C11H13ClFNO4: C, 47.58; H, 4.72; N, 5.04. Found: N,
47.39; H, 4.71; N, 5.02
0
–
out on precoated plate (silica gel 60 F254), and spots were
visualized with ultraviolet light. All chemicals or reagents
were purchased from standard commercial suppliers.
or refluxed for 2–8 h. Then, the solvent was evaporated
under reduced pressure to give the crude product, it could be
used to the next reaction directly.
3.3. General synthetic procedure for substituted
phenylimino-thiazolidine (1)
3.1. Synthesis of fluorophenyl isothiocyanate
To a stirred solution of sodium hydroxide (2.40 g,
0.06 mol) in 30 ml H2O, carbon disulfide (4.57 g, 0.06 mol)
was added at 2–5 8C, then, substituted aniline (0.06 mol)
was added over a period of 30 min. After the mixture was
refluxed for 24 h, ethyl chloroformate (6.51 g, 0.06 mol) was
added dropwise at 35–40 8C and the resulting mixture was
stirred for about 40 min at the same temperature. The
organic phase was separated and washed with water, dried
over anhydrous magnesium sulfate and concentrated under
reduced pressure and the residue was distilled to give
colorless liquid.
Appropriate thiourea (10 mmol) was dissolved in con-
centrated HCl (10 ml) and heated at 90 8C for 45 min. The
cooled mixture was basified with 10 N NaOH in an ice bath.
The solid was filtered and recrystallized or the precipitated
gummy residue was extracted with Et2O. The extract was
washed with brine, dried and evaporated to dryness.
3.4. General synthetic procedure for substituted
phenylimino-oxazolidine (2)
Substituted thiourea (0.01 mol) was dissolved in
CH3COCH3/Et2O (1:6 v/v, 30 ml). To the reaction mixture
was added in batch yellow HgO (15 g, 0.07 mol). After 24 h,
the resulting mixture was filtered through silica gel, and the
filtrate was concentrated under reduced pressure to give the
crude products, which were purified on TLC plates to give
the desired products.
3.2. Synthetic procedure for substituted thiourea
Appropriate amine was dissolved in ethyl acetate, and
appropriate isothiocyanate was added dropwise with stirring
and the mixture was kept at room temperature for 30–60 min
Fig. 2. The molecular structure, X-ray crystal structure and stacking spectrum of trifluorophenyl dimethylthiazolidine (1k).

X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
1619
Scheme 6.
Fig. 3. The molecular structure, X-ray crystal structure and stacking spectrum of o-fluorophenylimino-thiazolidine.
3.5. General synthetic procedure for substituted
phenylimino-oxazolidine (3) and (4)
the reaction mixture was stirred for 1 h at room temperature
and left overnight. The solvent was removed under reduced
pressure to give the crude product, which was recrystallized
from ethanol to give a white solid.
Substituted thiourea (0.01 mol), 30 ml CH3COCH3,
30 ml CH3OH were added in 100 ml flask. To the reaction
mixture was added in batch yellow HgO (21.6 g, 0.10 mol).
After 24 h, the resulting mixture was filtered, and the filtrate
was concentrated under reduced pressure to give the crude
products, which was recrystallized from ethanol to give the
desired products.
3.7. General synthetic procedure for fluorine-containing
N,N0-diphenylcarbamidothioates (5)
To a solution of the above thiourea (0.005 mol) in 50 ml
of methanol was added methyl iodide (0.85 g, 0.006 mol)
and the mixture was heated to reflux for 6 h. Then the solvent
was removed under reduced pressure and the residue was
added 50 ml of H2O and 10 ml of concentrated aqueous
ammonia. The precipitated product was filtered, washed
with H2O, and recrystallized from C2H5OH–H2O (4:10 v/v)
to give a white solid.
3.6. General synthetic procedure for N,N0-fluorosubstituted
diphenylthioureas (the intermediates of compound 5)
To a solution of the fluorine-containing aniline (0.01 mol)
in 50 ml of ethanol was added dropwise the aryl
isothiocyanate (0.01 mol) over a period of 10 min. Then
Scheme 7.

1620
X. Qian et al. / Journal of Fluorine Chemistry 125 (2004) 1609–1620
[10] S. Ogawa, C. Uchida, Chem. Lett. (1993) 173–176.
[11] C. Uchida, T. Yamagishi, S. Ogawa, J. Chem. Soc., Prekin Trans. 1
(1994) 589–602.
3.8. General synthetic procedure for compound (6)
To a mixture of fluoro-substituted aniline (0.01 mol),
D-glucose (0.01 mol) and water (8 ml) was added 1 ml of a
6% HCl solution. The mixture was kept for 10 min at 60 8C
and then cooled to 0 8C. The resulting mass was filtered,
washed with 2 ml water, dried and recrystallized from
C2H5OH to give white solids.
[12] K. Yoshiyuki, M. Hideki, S. Masao, J. Org. Chem. 59 (1994) 813–
822.
[13] J.S. Clegg, D.R. Evans, J. Exp. Biol. 38 (1961) 771.
[14] Y. Ohkuma, T. Kinoshita, R. Enokita, J. Antibiot. 44 (1991) 1165–
1168.
[15] S. Murao, S. Miyata, Agric. Biol. Chem. 44 (1980) 219–221.
[16] L. Vertesy, H.-W. Fehlhaber, A. Schulz, Angew. Chem. Int. Ed. Engl.
33 (1994) 1844–1846.
[17] R. Shigemoto, T. Okuno, K. Matura, Phytopathol. Soc. Jpn. 55 (1989)
238.
4. Conclusion
[18] Y. Kameda, N. Asano, T. Yamaguchi, K. Matsui, J. Antibiot. 40 (1987)
563–565.
Based on the structural features of trehazolin, six series of
compounds were designed and synthesized. Some facile and
convenient synthetic methods were obtained for the synthesis
of fluorine-containing arylisothiocyanate and fluorophenyl
aminobenzoxazoles, respectively. X-ray crystal analysis
suggested the presence of novel intermolecular (aromatic
CH3 ꢀ ꢀ ꢀ FCsp2) and intramolecular (NH ꢀ ꢀ ꢀ FCsp2) hydrogen
bonds with fluorine as an acceptor. Bio-screening showed that
some of compounds had significant fungicidal activity to R.
solani and P. oryzae in vitro at 100 ppm or good bioactivity at
1000 ppm in vivo.
[19] B.L. Rhinehart, K.M. Robinson, C.-H.R. King, Biochem. Pharmacol.
39 (1990) 1537–1543.
[20] C. Uchida, H. Kitahashi, S. Watanabe, S. Ogawa, J. Chem. Soc., Perkin
Trans. 1 (1995) 1707–1710.
[21] M. Hudlicky, Chemistry of Organic Fluorine Compounds, vol. II,
American Chemical Society, Washington, DC, 1995, pp. 979, 1145.
[22] X. Qian, Z. Liu, Z.B. Li, Z. Li, G. Song, J. Agric. Food Chem. 49
(2001) 5279–5284.
[23] X. Qian, Z.B. Li, Z. Liu, G. Song, Z. Li, J. Antibiot. 54 (2001) 1108–
1110.
[24] Z. Li, X. Qian, G. Song, Z. Li, J. Fluorine Chem. 108 (2001) 143–146.
[25] X. Qian, Z. Li, Z. Liu, G. Song, Z. Li, Carbohydr. Res. 336 (2001) 79–
82.
[26] L. Prakash, S.S. Verma, Shaihla, E. Tyagi, R.L. Mital, J. Fluorine
Chem. 41 (1988) 303–310.
Acknowledgements
[27] J. Gilmore, P.T. Gallagher, in: A.R. Katritzky, O. Meth-Cohn, C.W.
Rees (Eds.), Comprehensive Organic Functional Group Transforma-
tion, vol. 5, Pergamon Press, Oxford, 1995, p. 1021.
[28] W.S. Wadsworth, W.D. Emmons, J. Org. Chem. 32 (1967) 1279–1285.
[29] T. Besson, J. Guillard, C.W. Rees, V. Thiery, J. Chem. Soc., Perkin
Trans. 1 (1998) 889–892.
This work was partly supported by National Key Project
for Basic Research (2003CB114405), National Natural
Science Foundation of China.
[30] J.E. Hodgkins, W.P. Reeves, J. Org. Chem. 29 (1964) 3098–3099.
[31] Z.B. Li, X.H. Qian, Z. Liu, Z. Li, G.H. Song, Org. Prep. Proc. Int. 32
(2000) 571–573.
References
[32] H. Ogura, S. Mineo, K. Natagawa, Chem. Pharm. Bull. 29 (1981)
1518–1520.
[1] T. Iwase, E. Higashide, H. Yamamoto, M. Shitata, J. Antibiot. 24
(1971) 107–113.
[33] H.S. Chang, G.H. Yon, Y.H. Kim, Chem. Lett. 8 (1986) 1291–1294.
[34] A. Mosen, M.E. Omar, N.S. Habib, O.M. Aboulwafa, Synthesis (1977)
864–865.
[2] O. Ando, M. Nakajima, M. Kifune, H. Fang, K. Tanzawa, Biochim.
Biophys. Acta 1244 (1995) 295–302.
[35] C.J. Pages, Germany Patent 2 221 866 (1971); Chem. Abstr. 78 (1972)
58395j.
[3] O. Ando, M. Klfune, M. Nakajima, Biosci. Biotechnol. Biochem. 59
(1995) 711–712.
[36] X. Qian, Z. Li, G. Song, Z. Li, J. Chem. Res. Synop. 4 (2001) 138–139.
[37] T.J. Barbrich, C.D. Rithner, S.M. Miller, O.P. Anderson, S.H. Strass, J.
Am. Chem. Soc. 121 (1999) 4280–4281.
[4] O. Ando, H. Satake, K. Itoil, A. Sato, M. Nakajima, H. Haruyama, Y.
Ohkuma, T. Kinoshita, R. Enokita, J. Antibiot. 44 (1991) 1165–1168.
[5] Y. Kobayashi, Carbohydr. Res. 315 (1999) 3–15.
[6] Y. Kobayashi, H. Miyazaki, M. Shiozaki, J. Antibiot. 47 (1994)
932–938.
[38] J.A.K. Howard, V.J. Hoy, D. O’Hagan, G.T. Smith, Tetrahedron 52
(1996) 12613–12622.
[39] J.L. Alonso, S. Antolinez, S. Blanco, A. Lesami, J.C. Lopez, W.
Caminat, J. Am. Chem. Soc. 126 (2004) 3244–3249.
[40] T. Sakai, Y. Miki, M. Nakatani, T. Ema, K. Uneyama, M. Utaka,
Tetrahedron Lett. 29 (1998) 5233–5236.
[7] T. Nakayama, T. Amachi, S. Murao, T. Sakai, T. Shin, P.T. Kenny, T.
Iwashita, M. Zagorski, H. Komura, K. Nomoto, J. Chem. Soc., Chem.
Commun. (1991) 919–920.
[8] B.M. Trost, D.L. Van Vrankon, J. Am. Chem. Soc. 115 (1993) 444–
458.
[41] K. Hostettmann, J.B. Harborne, P.M. Dey, Methods in Plant Biochem-
istry, vol. 6, Academic Press, London, UK, 1991, pp. 33–46.
[9] J. Li, F. Lang, B. Ganem, J. Org. Chem. 63 (1998) 3403–3410.