Synthesis and fungicidal activity of 1,3-thiazoline derivatives bearing nitrophenyl group on the 2-position

Article abstract of DOI:10.1002/jhet.570

Ortho-, meta-, or para-nitro benzoic acid were refluxed with excess SOCl₂ to give acyl chloride, which condensed with β-amino alcohol in the presence of Et₃N in dichloromethane to afford β-hydroxyamide; finally, sulphonation and cycl

Full text of DOI:10.1002/jhet.570

May 2011
Synthesis and Fungicidal Activity of 1,3-Thiazoline Derivatives
Bearing Nitrophenyl Group on the 2-Position
729
Qiuying Zhao,a,b Jing Li,a,b Xiaojing Yan,a,b Huizhu Yuan,a,b
*
Zhaohai Qin,a,b and Bin Fua,b
*
aKey Laboratory of Pesticide Chemistry and Application Technology, Department of Applied
Chemistry, China Agricultural University, Beijing 100193, People’s Republic of China
bInstitute of Plant Protection, Chinese Academy of Agricultural Science, Beijing 100193,
People’s Republic of China
*E-mail: hzhyuan@gmail.com or fubinchem@cau.edu.cn
Received April 29, 2010
DOI 10.1002/jhet.570
Published online 28 March 2011 in Wiley Online Library (wileyonlinelibrary.com).
Ortho-, meta-, or para-nitro benzoic acid were refluxed with excess SOCl2 to give acyl chloride,
which condensed with b-amino alcohol in the presence of Et3N in dichloromethane to afford b-hydrox-
yamide; finally, sulphonation and cyclization were simultaneously conducted to afford 1,3-thiazoline
derivatives. Fungicidal activity of these new thiazolines against eight agrocultural fungi were evaluated,
and two of this type of compounds displayed good fungicidal activity comparable or superior to com-
mercial fungicide chlorothalonil against two fungi at a concentration of 50 mg/L.
J. Heterocyclic Chem., 48, 729 (2011).
INTRODUCTION
in biological activities as a continuation of our research
interest in thiazoline chemistry [17,10], herein we would
like to report the synthesis and fungicidal activity of 2-
Thiazoline rings have been found in a large number
of biological active natural products, such as thiangazole
[1], curacin A [2], and lissoclinamides [3]. Moreover,
thiazoline compounds have been widely applied as food
additives [4], agrochemicals [5], chiral catalysts [6], and
so on. In view of the versatile properties of thiazoline
compounds, to date, many methods have been developed
for the construction of thiazoline ring system [7–10]. In
recent years, direct cyclization of b-hydroxyamide has
been used as one convenient method for its simplicity
and practicability. Some mono-, bis- and tris-thiazoline
compounds have been synthesized with Lawesson rea-
gent or phosphorus pentasulfide (P2S5) as cyclizing rea-
gent [11–13]. The 1,3-thiazolines with aryl or tertiary
alkyl group at 2-position can be synthesized conven-
iently by this method.
(o-, m-,
derivatives.
p-)nitrophenyl-substituted
1,3-thiazoline
RESULTS AND DISCUSSION
The synthetic pathway to the title thiazoline involves
one-pot and three-step sequence [13]. The starting mate-
rial m- or p-nitrophenyl carboxylic acid was refluxed in
SOCl2 for 12 h and the excess SOCl2 was removed
in vacuo. The crude acyl chlorides were dissolved in
CH2Cl2 and added dropwise to the solution of amino
alcohols and Et3N in CH2Cl2 at 0ꢀC. After being stirring
for 4 h, the solvent was removed in vacuo, and the
crude intermediate b-hydroxyamides were used in the
cyclization step without further purification. The mixture
of P2S5 with b-hydroxyamides was refluxed in toluene
for 4–6 h in the presence of Et3N. The desired thiazo-
lines 4 and 5 bearing p- or m-nitrophenyl at 2-position
were obtained in 65–90% yield after column chromato-
graphic purification. However, the thiazoline 6 with o-
nitrophenyl at 2-position was not obtained following the
same procedure, to our surprise, the thiazoline com-
pounds bearing o-aminophenyl at 2-position was
Usually, different substituents on the thiazoline ring
have different effects on the biological activity and other
properties. Nitro group is an important substituted group
which existed in a number of pharmaceuticals and agro-
chemical products [14–16]. Owing to its strong electron-
withdrawing property and regio effect at different posi-
tion on the aryl ring, the biological activity of the com-
pounds containing nitro group can be tuned well. To
further explore the application of thiazoline derivatives
C
V
2011 HeteroCorporation

730
Q. Zhao, J. Li, X. Yan, H. Yuan, Z. Qin, and B. Fu
Vol 48
Scheme 1
amount of P2S5 to 1 equiv. and other reaction condition
was not changed, no desired product was produced, then
the cyclization reagent was changed. Lawesson reagent
was used in the cyclizing step to lead to the expected
thiazoline 6; however, the yield was only in 16–40% af-
ter purification (Scheme 1). The structure of new nitro-
phenyl thiazoline compounds were characterized by
spectroscopic methods.
Bioassay of fungicidal activities. Fungicidal activ-
ities of the title compounds against eight agrocultural
fungi (including: Rhizoctonia solani Ku¨hn; Botrytis cin-
erea Pers.; Phytophthora parasitica Dast.; Sclerotinia
sclerotiorum (Lib.) de Bary; Valsa mali Miyabe et
Yamada; Phytophthora capsici Leon; Phomopsis aspar-
agi (Sacc.) Bubak; and Pyricularia oryzae Cav.) were
evaluated at 50 lg/mL using the mycelium growth rate
test. All results were outlined in Table 1. Most com-
pounds showed some fungicidal activities in vitro against
the above eight strains. Among them, the thiazoline 6a–e
bearing o-nitrophenyl group at 2-position showed low to
common fungicidal activity. 4b and 5b with i-propyl
group showed good activity against B. cinerea Pers with
inhibitory rates of 79.6 and 87.9%; in addition, 4b and
5b showed good activity against P. oryzae Cav. with in-
hibitory rates of 81.1 and 90.9%, respectively, and the
fungicidal activity was comparable and better than that
of the commercial fungicide chlorothalonil.
CONCLUSIONS
produced, that is to say, the nitro group was reduced to
the amino group when the thiazoline ring formed under
the presence of excess P2S5, even if decreasing the
In conclusion, a series of 2-(p-, m-, o-nitrophenyl) thi-
azoline compounds were synthesized via convenient
Table 1
Fungicidal activity of compounds 4a–e, 5a–e, and 6a–e.
The rate of inhibition
Rhizoctonia
solani
Ku¨hn
Botrytis
cinerea
Pers.
Phytophthora
parasitica
Dast.
Sclerotinia
sclerotiorum
(Lib.) de Bary
Valsa mali
Miyabe et
Yamada
Phomopsis
asparagi
(Sacc.) Bubak
Phytophthora
capsici Leon
Pyricularia
oryzae Cav.
Compounds
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
6a
6b
6c
6d
66.6
73.3
72.4
29.0
48.3
70.6
61.7
45.8
37.7
48.8
34.6
34.1
62.2
29.2
43.0
87
74.5
79.6
59.4
52.0
38.4
68.8
87.9
20.0
21.1
40.6
39.1
38.7
60.5
53.0
45.5
76
64.6
57.9
35.8
9.3
36.6
32.0
20.3
76.0
25.2
38.6
8.9
39.0
7.7
0
37.8
15.0
52.1
11.7
29.1
55.2
56.8
38.8
33.4
31.1
11.7
40.8
50.8
28.4
21.4
92
53.8
57.2
4.8
4.0
50.6
ꢁ8.0
50.7
26.7
37.3
32.0
13.9
38.7
0
55.9
81.1
34.5
21.9
38.7
37.6
90.9
68.0
27.2
34.5
20.9
39.7
49.2
49.2
29.3
84
2.2
29.2
60.2
58.0
6.7
24.8
44.7
27.0
0
41.4
36.6
30.7
25.5
29.6
0
23.7
33.9
33.9
0
0
0
0
0
0
56.7
0
0
44.7
27.0
65
0
6e
Chlorothalonil
29.3
100
2.2
55
57.3
79
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2011
Synthesis and Fungicidal Activity of 1,3-Thiazoline Derivatives Bearing Nitrophenyl
Group on the 2-Position
731
163.87. IR (cmꢁ1): 2955, 1593, 1522, 1347, 1007, 858, 690.
Anal. Calcd for C13H16N2O2S (264.35): C 59.07, H 6.10, N
10.60. Found: C 59.35, H 6.25, N 10.45.
method, their fungicidal activity against eight agrocul-
tural fungi were evaluated. The 2-(p-, m-)nitrophenylth-
iazoline with 4-iso-propyl group displayed good fungici-
dal activities against two agrocultural fungi compared
with commercial fungicide chlorothalonil.
4d. Mp: 116–117ꢀC. 1H-NMR (300 MHz, CDCl3): d 8.24–
8.27 (m, 2H, ArH), 7.97–8.02 (m, 2H, ArH), 7.24–7.37 (m,
5H, ArH), 4.93–5.03 (m, 1H, CHN¼¼), 3.42 (dd, J ¼ 8.35,
11.14 Hz, 1H), 3.20–3.34 (m, 2H, CH2), 2.88 (dd, J ¼ 8.73,
13.63 Hz,1H). 13C-NMR (75 MHz, CDCl3): d 37.84, 40.16,
78.98, 123.58, 126.61, 128.55, 129.18, 129.25, 138.02, 138.76,
149.22, 165.28. IR (cmꢁ1): 2930, 1510, 1495, 1336, 1230,
1108, 740. Anal. Calcd for C16H14N2O2S (298.369): C 64.41,
H 4.73, N 9.39. Found: C 64.55, H 4.88, N 9.43.
EXPERIMENTAL
NMR spectra were recorded on a Bruker Avance DPX300
spectrometer with tetramethylsilane as internal standard and
CDCl3 as solvent. Infrared spectra were obtained on a Nicolet
AVATAR 330 FTIR spectrometer. Elemental analyses were
carried out on an Elementar Vario EL instrument. Melting
points were measured on an XT-4 melting point apparatus and
were uncorrected. Solvents were purified and dried following
standard procedures.
1
4e. Mp: 85.0–86.0ꢀC. H-NMR (300 MHz, CDCl3): d 8.27–
8.32 (m, 2H, ArH), 8.07–8.11 (m, 2H, ArH), 7.33–7.42 (m,
5H, ArH), 5.76 (t, J ¼ 9.33 Hz, 1H, CHN¼¼), 3.90 (dd, J ¼
8.85, 11.06 Hz, 1H), 3.42 (dd, J ¼ 9.81, 11.05 Hz, 1H); 13C-
NMR (75 MHz, CDCl3): d 41.72, 81.55, 124.46, 127.39,
128.80, 129.67, 130.21, 139.58, 142.20, 150.36, 167.58. IR
(cmꢁ1): 1593, 1521, 1349, 1026, 851, 754, 690. Anal. Calcd
for C15H12N2O2S (284.342): C 63.36, H 4.25, N 9.85. Found:
C 63.36, H 4.36, N 9.69.
5a. Mp: 49.0–50.0ꢀC. 1H-NMR (300 MHz,CDCl3): d 8.67
(t, J ¼ 1.92 Hz, 1H, ArH), 8.28–8.33 (m, 1H, ArH), 8.12–8.16
(m, 1H, ArH), 7.57–7.62 (m, 1H, ArH), 4.77–4.84 (m, 1H,
CHN¼¼), 3.62 (dd, J ¼ 10.88, 8.28 Hz, 1H), 3.13 (dd, J ¼
10.88, 7.77 Hz, 1H), 1.49 (d, J ¼ 6.72 Hz, 3H, CH3). 13C-
NMR (75 MHz, CDCl3): d 20.3, 40.5, 73.1, 123.2, 125.4,
129.4, 133.9, 135.0, 148.2, 164.3. IR (cmꢁ1): 2981, 1567,
1517, 1345, 1110, 960, 836, 681. Anal. Calcd for
C10H10N2O2S (222.271): C 54.04, H 4.54, N 12.60. Found: C
54.28, H 4.50, N 12.69.
General procedure for the synthesis of thiazoline 4a–e,
5a–e. The p- or m-nitrobenzoic acid (0.5 g, 2.99 mmol) was
refluxed with SOCl2 (3.0 mL) for 12 h, then the excess SOCl2
was removed in vacuo. Benzene (5 mL) was added and
removed again to dryness to remove the trace amount of
SOCl2 and afforded the acyl chloride. The acyl chloride in
CH2Cl2 (15 mL) was added dropwise to a solution of amino
alcohol (3.10 mmol) and Et3N (2 mL, 14.5 mmol) in CH2Cl2
(15 mL) at 0ꢀC and stirred at room temperature for 4–6 h. The
reaction mixture was evaporated to remove the solvent in
vacuo, and toluene (20 mL) and Et3N (4 mL, 28.9 mmol)
were added to the crude hydroxyl amide, P2S5 (1.0 g, 4.5
mmol) was added under refluxing in three portions within 1 h,
and the suspension was continued to reflux for another 4–6 h.
After being cooled to room temperature, the solution was
washed with H2O (5 mL ꢂ 2), dried over anhydrous Na2SO4,
and concentrated to give the crude product. Column chromato-
graphic purification on silica gel (V/V, ethyl acetate/petroleum
ether, 1:5) afforded the thiazoline compounds 4a–e and 5a–e.
5b. Mp: 53.5–54.5ꢀC. 1H-NMR (300 MHz, CDCl3): d 8.64
(t, J ¼ 1.85 Hz, 1H, ArH), 8.28 (dd, J ¼ 1.32, 8.21 Hz, 1H,
ArH), 8.12 (d, J ¼ 8.85 Hz, 1H, ArH), 7.59 (t, J ¼ 7.76 Hz,
1H, ArH), 4.41–4.49 (m, 1H, CHN¼¼), 3.49 (dd, J ¼ 8.80,
10.92 Hz, 1H), 3.22 (t, J ¼ 9.88 Hz, 1H), 2.04–2.15 (m, 1H,
CH), 1.13 (d, J ¼ 6.75 Hz, 3H, CH3), 1.03 (t, J ¼ 6.75 Hz,
3H, CH3). 13C-NMR (75 MHz, CDCl3): d 18.87, 19.50, 33.07,
35.87, 84.08, 122.72, 124.99, 129.17, 133.72, 134.82, 147.89,
163.52. IR (cmꢁ1): 2985, 1603, 1565, 1009, 947, 785, 697.
Anal. Calcd for C12H14N2O2S (250.325): C 57.58, H 5.64, N
11.19. Found: C 57.45, H 5.66, N 11.07.
1
4a. Mp: 57.0–58.0ꢀC. H-NMR (300 MHz, CDCl3): d 8.24–
8.28 (m, 2H, ArH), 7.97–8.01 (m, 2H, ArH), 4.77–4.85 (m,
1H, CHN¼¼), 3.62 (dd, J ¼ 8.34, 10.86 Hz, 1H), 3.13 (dd, J ¼
7.86, 10.89 Hz, 1H), 1.49 (d, J ¼ 6.72 Hz, 3H, CH3); 13C-
NMR (75 MHz, CDCl3): d 20.23, 40.43, 73.31, 77.2, 123.57,
129.18, 138.88, 149.20, 164.51. IR (cmꢁ1): 1588, 1519, 1361,
1317, 1110, 965, 860, 690. Anal. Calcd for C10H10N2O2S
(222.271): C 54.04, H 4.54, N 12.60. Found: C 54.25, H 4.25,
N 12.64.
1
5c. H-NMR (300 MHz, CDCl3): d 8.78 (t, J ¼ 1.89 Hz,
1H, ArH), 8.31–8.35 (m, 1H, ArH), 8.26–8.34 (m, 2H, ArH),
7.57–7.62 (m, 1H, ArH), 4.57 (dd, J ¼ 8.07, 9.39 Hz, 1H),
4.33–4.44 (m, 1H, CHN¼¼), 4.05 (t, J ¼ 8.04 Hz, 1H), 1.81–
1.90 (m, 1H, CH2), 1.67–1.76 (m, 1H, CH2), 1.36–1.45 (m,
1H, CH, 0.95–1.05 (m, 6H, CH3). 13C-NMR (75 MHz,
CDCl3): d 22.72, 22.76, 25.50, 45.48, 65.48, 73.65, 123.28,
125.64, 129.37, 129.85, 133.93, 148.23, 161.26. IR (cmꢁ1):
2982, 1536, 1349, 838, 758, 714, 681. Anal. Calcd for
C13H16N2O2S (264.35): C 59.07, H 6.10, N 10.60. Found: C
59.38, H 6.05, N 10.84.
4b. Mp: 49–51ꢀC. 1H-NMR (300 MHz, CDCl3): d 8.23–
8.28 (m, 2H, ArH), 7.97–8.01 (m, 2H, ArH), 4.43–4.51 (m,
1H, CHN¼¼), 3.49 (dd, J ¼ 8.82, 10.95 Hz, 1H), 3.22 (dd, J ¼
9.75, 10.95 Hz, 1H), 2.06–2.17 (m, 1H, CH), 1.13 (d, J ¼
6.75 Hz, 3H, CH3), 1.04 (d, J ¼ 6.75 Hz, 3H, CH3). 13C-NMR
(75 MHz, CDCl3): d 19.07, 19.71, 33.30, 36.06, 84.49, 123.55,
129.16, 139.01, 149.14, 164.16. IR (cmꢁ1): 2955, 1604, 1578,
1012, 785, 747, 697. Anal. Calcd for C12H14N2O2S (250.325):
C 57.58, H 5.64, N 11.19. Found: C 57.45, H 5.45, N 11.44.
5d. Mp: 56.0–57.0ꢀC. 1H-NMR (300 MHz, CDCl3): d 8.67
(t, J ¼ 1.89 Hz, 1H, ArH), 8.29–8.33 (m, 1H, ArH), 8.17–8.31
(m, 1H, ArH), 7.60 (t, J ¼ 7.83 Hz, 1H, ArH), 7.23–7.34 (m,
5H, ArH), 4.94–4.99 (m, 1H, CHN¼¼), 3.42 (dd, J ¼ 11.13,
8.31 Hz, 1H), 3.21–3.34 (m, 2H, CH2), 2.87 (dd, J ¼ 8.85,
16.80 Hz, 1H). 13C-NMR (75 MHz, CDCl3): d 37.85, 40.16,
78.82, 123.21, 125.52, 126.53, 129.27, 129.47, 133.94, 134.92,
138.06, 148.25, 165.17. IR: 1602, 1530, 1347, 1246, 725, 682.
1
4c. Mp: 38.5–39.5ꢀC. H-NMR (300 MHz, CDCl3): d 8.22–
8.27 (m, 2H, ArH), 7.95–8.00 (m, 2H, ArH), 4.68–4.78 (m,
1H, CHN¼¼), 3.75 (dd, J ¼ 8.35, 10.85 Hz,1H), 3.12 (dd, J ¼
8.39, 10.86 Hz, 1H), 1.78–1.96 (m, 2H, CH2), 1.47–1.56 (m,
1H, CH), 1.04 (d, J ¼ 6.49 Hz, 3H, CH3), 1.01 (d, J ¼ 6.18
Hz, 3H, CH3). 13C-NMR (75 MHz, CDCl3): d 22.51, 22.66,
25.80, 38.99, 44.04, 76.37, 123.39, 129.03, 138.84, 149.97,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

732
Q. Zhao, J. Li, X. Yan, H. Yuan, Z. Qin, and B. Fu
Vol 48
Anal. Calcd for C16H14N2O2S (298.369): C 64.41, H 4.73, N
9.39. Found: C 64.70, H 4.98, N 9.56.
Fungicidal testing. Fungicidal activity of compounds (4a–e,
5a–e, and 6a–e) were tested against eight fungal isolates
(including: R. solani Ku¨hn; B. cinerea Pers.; P. parasitica
Dast.; S. sclerotiorum (Lib.) de Bary; V. mali Miyabe er
Yamada; P. capsici Leon; P. asparagi (Sacc.) Bubak; and
P. oryzae Cav.) provided by Institute of Plant Protection, Chi-
nese Academy of Agricultural Sciences. Two negative con-
trols: one with acetone, the solvent of all tested compounds
(no antifungal activity has been noted) and the other as
untreated potato dextrose agar petri dishes used using the agar
growth medium poison technique. The medium was potato
dextrose agar and the concentration of the tested compounds
was 50 ppm. After 5-days incubation at 25ꢀC, the growth di-
ameter of treatments was measured, and the percentage inhibi-
tion of growth for each compound was determined based on
the negative control growth of each fungal species under the
same incubation conditions. Chlorothalonil as a reference was
included to compare with compounds. All tests were per-
formed in triplicate and the average results, as a percentage
(%) of the inhibition rate calculated according to the formula:
1
5e. H-NMR (300 MHz, CDCl3): d 8.76 (t, J ¼ 1.96 Hz,
1H, ArH), 8.31–8.35 (m, 1H, ArH), 8.21–8.25 (m, 1H, ArH),
7.62 (t, J ¼ 7.80 Hz, 1H, ArH), 7.32–7.40 (m, 5H, ArH), 5.75
(t, J ¼ 9.18 Hz, 1H, CHN¼¼), 3.90 (dd, J ¼ 11.06, 8.81
Hz,1H), 3.42 (dd, J ¼ 11.04, 9.67 Hz, 1H). 13C-NMR (75
MHz, CDCl3): d 41.34, 80.76, 123.24, 125.60, 127.80, 128.72,
129.48, 134.05, 134.73, 141.31, 148.20, 166.15. IR: 1603,
1528, 1346, 1010, 857, 755, 698. Anal. Calcd for
C15H12N2O2S (284.342): C 63.36, H 4.25, N 9.85. Found: C
63.54, H 4.10, N 9.99.
General procedure for the synthesis of thiazoline 6a–e,
all the procedure was the same as the synthesis of 4a–e,
except for using Lawesson reagent in place of P2S5
1
6a. H-NMR (300 MHz, CDCl3): d 7.94–7.98 (m, 1H,
ArH), 7.70–7.92 (m, 2H, ArH), 7.61–7.67 (m, 1H, ArH), 4.80–
4.88 (m, 1H, CHN¼¼), 3.72 (dd, J ¼ 8.26, 10.78 Hz, 1H), 3.25
(dd, J ¼ 7.34, 10.77 Hz, 1H), 1.52 (d, J ¼ 6.73 Hz, 3H, CH3).
13C-NMR (75 MHz, CDCl3): d 19.52, 41.34, 73.48, 124.12,
128.90, 130.37, 130.66, 132.44, 148.31, 162.28. IR (cmꢁ1):
2919, 1602, 1574, 1530, 1493, 1351, 1020, 946, 769, 742,
698. Anal. Calcd for C10H10N2O2S (222.271): C 54.04, H
4.54, N 12.60. Found: C 54.35, H 4.34, N 12.88.
D21 ꢁ D20
I ¼
ꢂ 100%
D12
1
6b. H-NMR (300 MHz, CDCl3): d 7.83–7.86 (m, 1H,
ArH), 7.51–7.62 (m, 3H, ArH), 4.37–4.46 (m, 1H, CHN¼¼),
3.49 (dd, J ¼ 8.77, 10.80 Hz, 1H), 3.28 (dd, J ¼ 9.88, 10.80
Hz, 1H), 2.06–2.13 (m, 1H, CH), 1.07 (d, J ¼ 6.76 Hz, 3H,
CH3), 1.03 (d, J ¼ 6.76 Hz, 3H, CH3). 13C-NMR (75 MHz,
CDCl3): d 19.10, 19.56, 32.83, 36.85, 84.78, 123.99, 128.85,
130.35, 130.56, 132.27, 148.37, 162.07. IR (cmꢁ1): 2955,
1605, 1565, 1002, 940, 782, 749, 697. Anal. Calcd for
C12H14N2O2S (250.325): C 57.58, H 5.64, N 11.19. Found: C
57.42, H 5.52, N 11.39.
Acknowledgments. The authors are grateful to the Chinese Uni-
versities Scientific Fund (2009-1-31) and Key Laboratory of Pes-
ticide Chemistry and Application (MOAPCA201002) for
financial support.
REFERENCES AND NOTES
[1] Jansen, R.; Kunze, B.; Reichenbach, H.; Jurkiewicz, E.;
¨
Hunsmann, G.; Hofle, G. Liebigs Ann Chem 1992, 357.
1
6c. H-NMR (300 MHz, CDCl3): d 7.85–7.89 (m, 1H,
[2] White, J. D.; Kim, T.-S.; Nambu, M. J Am Chem Soc
1995, 117, 5612.
ArH), 7.61–7.65 (m, 2H, ArH), 7.52–7.59 (m, 1H, ArH), 4.64–
4.75 (m, 1H, CHN¼¼), 3.59 (dd, J ¼ 8.31, 10.74 Hz, 1H), 3.17
(dd, J ¼ 7.92, 10.74 Hz, 1H), 1.76–1.87 (m, 2H, CH2), 1.44–
1.52 (m, 1H, CH), 0.97–1.01 (m, 6H, CH3); 13C NMR (75
MHz, CDCl3): d 22.54, 22.89, 26.18, 36.82, 44.62, 76.10,
114.91, 115.85, 116.14, 131.33, 132.25, 147.51, 167.13. IR
(cmꢁ1): 2960, 1604, 1534, 1367, 1019, 985, 968, 783, 752.
Anal. Calcd for C13H16N2O2S (264.35): C 59.07, H 6.10, N
10.60. Found: C 59.31, H 6.29, N 10.75.
[3] Pattenden, G.; Michael, J. P. Angew Chem Int Ed Engl
1993, 32, 1.
[4] Adams, A.; De Kimpe, N. Chem Rev 2006, 106, 2299.
[5] George, B.; Papadopoulos, E. P. J Org Chem 1977, 42, 441.
[6] Gaumont, A.-G.; Gulea, M.; Levillain, J Chem Rev 2009,
109, 1371.
[7] (a) Boden, C. D. J.; Pattenden, G.; Ye, T. Synlett 1995,
417; (b) Katritzky, A. R.; Cai, C. M.; Suzuki, K.; Singh, S. K. J Org
Chem 2004, 69, 811.
1
6d. H-NMR (300 MHz, CDCl3): d 7.87–7.90 (m, 1H,
[8] Kim, T.-S.; Lee, Y.-J.; Jeong, B.-S.; Park, H.-G.; Jew, S.-S.
J Org Chem 2006, 71, 8276.
ArH), 7.55–7.64 (m, 3H, ArH), 7.24–7.35 (m, 5H, ArH), 4.90–
4.96 (m, 1H, CHN¼¼), 3.45 (dd, J ¼ 8.31, 11.04 Hz, 1H),
3.23–3.29 (m, 2H, CH2), 2.82–2.90 (m, 1H); 13C-NMR (75
MHz, CDCl3): d 38.77, 39.40, 79.35, 124.21, 126.54, 128.56,
128.92, 129.27, 130.43, 130.74, 132.45, 138.21, 163.31. IR
(cmꢁ1): 2918, 1601, 1530, 1358, 945, 749, 702. Anal. Calcd
for C16H14N2O2S (298.369): C 64.41, H 4.73, N 9.39. Found:
C 64.65, H 4.96, N 9.54.
[9] Wipf, P.; Miller, C. P. Tetrahedron Lett 1992, 33, 6267.
[10] Cheng, X. M.; Zheng, Z. B.; Li, N.; Qin, Z. H.; Fu, B.;
Wang, N. D. Tetrahedron: Asymmetry 2008, 19, 2159.
[11] Tarrage, A.; Molina, P.; Curiel, D.; Bautista, D. Tetrahe-
dron: Asymmetry 2002, 13, 1621.
[12] Fu, B.; Du, D. M.; Xia, Q. Synthesis 2004, 221.
[13] Lu, X. H.; Qi, Q. Q.; Xiao, Y. M.; Li, N.; Fu, B. Hetero-
cycles 2009, 78, 1031.
1
6e. H-NMR (300 MHz, CDCl3): d 7.90–7.93 (m, 1H,
ArH), 7.57–7.68 (m, 3H, ArH), 7.30–7.40 (m, 5H, ArH), 5.65
(dd, J ¼ 7.80, 10.68 Hz, 1H, CHN¼¼), 3.89 (dd, J ¼ 7.80,
10.98 Hz, 1H), 3.45 (d, J ¼ 10.80 Hz, 1H); 13C-NMR (75
MHz, CDCl3): d 42.52, 81.43, 124.28, 126.65, 127.73, 128.70,
128.96, 130.34, 130.81, 132.60, 133.4, 141.35, 148.23, 164.55.
IR (cmꢁ1): 2918, 2849, 1603, 1530, 1351, 1019, 846, 757,
698. Anal. Calcd for C15H12N2O2S (284.342): C 63.36, H
4.25, N 9.85. Found: C 63.46, H 4.46, N 9.60.
[14] Carollo, C. A.; de Siqueira, J. M. Nat Prod Res 2009, 23,
633.
[15] Hidalgo, W.; Duque, L.; Saez, J.; Arango, R.; Gil, J.; Rojano,
B.; Schneider, B.; Otalvaro, F. J Agric Food Chem 2009, 57, 7417.
[16] Klinkhammer, W.; Mu¨ller, H.; Globisch, C.; Pajeva, I. K.
Bioorg Med Chem 2009, 17, 2524.
[17] Yu, Y.-B.; Chen, H.-L.; Wang, L.-Y.; Chen, X.-Zh.; Fu, B.
Molecules 2009, 14, 4858.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet