3-hydrazido and 3-hydrazono derivatives of tenuazonic acid and their herbicide evaluation

Article abstract of DOI:10.1002/jhet.1939

With the aim of optimizing the structure of tenuazonic acid and improving the herbicidal activity, hydrazine moieties were introduced to the 3-position of pyrrolidine-2,4-dione scaffold of tenuazonic acid. 3-Hydrazido-pyrrolidine-2,4- dione compounds (4a, 4b, 4c, 4d, 4e) were prepared from corresponding carboxylates and hydrazines via a microwave-assisted amidation, whereas 3-hydrazono compounds (7a, 7b, 7c, 7d, 7e) were prepared from corresponding 3-acetyl pyrrolidine-2,4-dione. Both of the two structures also exhibited herbicidal activities, especially against the dicotyledonous species amaranth pigweed (Amaranthus retroflexus), but with different structure-activity relationship.

Full text of DOI:10.1002/jhet.1939

August 2014 3-Hydrazido and 3-Hydrazono Derivatives of Tenuazonic Acid and their
Herbicide Evaluation
E197
a
a
a
b
a
Yu-Xiu Liu, Zhi-Peng Cui, Yong-Hong Li, Yu-Cheng Gu, and Qing-Min Wang *
a
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai
University, Tianjin 300071, People’s Republic of China
Syngenta, Jealott’s Hill International Research Centre, Bracknell, Berks, RG42 6EY, UK
b
*
E-mail: wangqm@nankai.edu.cn
Received October 17, 2012
DOI 10.1002/jhet.1939
Published online 22 April 2014 in Wiley Online Library (wileyonlinelibrary.com).
With the aim of optimizing the structure of tenuazonic acid and improving the herbicidal activity,
hydrazine moieties were introduced to the 3-position of pyrrolidine-2,4-dione scaffold of tenuazonic acid.
3
-Hydrazido-pyrrolidine-2,4-dione compounds (4a–e) were prepared from corresponding carboxylates and
hydrazines via a microwave-assisted amidation, whereas 3-hydrazono compounds (7a–e) were prepared
from corresponding 3-acetyl pyrrolidine-2,4-dione. Both of the two structures also exhibited herbicidal
activities, especially against the dicotyledonous species amaranth pigweed (Amaranthus retroflexus), but
with different structure-activity relationship.
J. Heterocyclic Chem., 51, E197 (2014).
INTRODUCTION
benzylidene]pyrrolidine-2,4-diones (Fig. 1, A) were the most
successful representatives [4,5]. They exhibited good her-
bicidal activities especially against the monocotyledonous
plants Echinochloa crus-galli and Digitaria sanguinalis
in preemergence treatments. 3-(1-Substituted-amino)
ethylidene-1H-pyrrolidine-2,4-diones [6] (Fig. 1, B) and 3-(1-
(alkyloxyamino)ethylidene)-1H-pyrrolidine-2,4-diones[7,8]
(Fig. 1, C) were also found to exhibit significant herbicidal
activity. However, these compounds may combine with
different targets therefore have different weed control
mechanisms [5,9,10].
Tenuazonic acid (TeA) (Figure 1, TeA), first isolated in
957 from the culture filtrates of a fungal strain of Alternaria
1
tenuis [1,2], was found to have versatile bioactivities includ-
ing antitumor, antiviral, antibacterial activities, and so on [3].
TeA was also found to have phytotoxic effects on a wide
range of plants including weed species and crop plants [3].
On the basis of the 2,4-diketone structure of TeA, series of
analogs were designed and synthesized to improve their
herbicidal activity, of which 3-[(a-hydroxy-substituted)
©
2014 HeteroCorporation

E198
Y-X. Liu, Z-P. Cui, Y-H. Li, Y-C. Gu, and Q-M. Wang
Vol 51
Figure 1. Tenuazonic acid (TeA) and designed herbicidal analogs. [Color figure can be viewed in the online issue,which is available at wileyon-
linelibrary.com.]
In this paper, we also focus our attention on the substituent
at the 3-position of the pyrrolid-2,4-dione unit, which is
reported to play an important role in the herbicidal activity
and mode of action. Hydrazines were introduced into the 3-
position of the pyrrolid-2,4-dione to prepare hydrazide and
hydrozone compounds (Fig. 1). Hydrazides and hydrozones
are common structure fragments widespread in pesticide
molecules. In the hydrazine compounds, the most successful
example may be the diacylhydrazine insect growth regula-
tors such as RH-5992 [11] and ANS-118 [12] (Fig. 1).
Hydrazone compound diflufenzopyr [13], which bearing
both urea and hydrazone structure (Fig. 1), was mainly used
for broadleaf weeds and gramineous weeds control in corn
field at a dosage of 13.3–26.2 g/hm. We wish the introduc-
tion of hydrazide and hydrozone group to 3-position of the
pyrrolid-2,4-dione bring novel herbicidal activity or other
unknown bioactivity.
easily decarboxylated when refluxing, microwave
irradiation was used for the reaction with hydrazines to
reduce the reaction time. Under this condition, the
hydrazidation was completed within only 15min and gave
3-hydrazido products (4a–e) in acceptable yields.
Representative alkyl, aryl, and alkoxyhydrazides were
selected to prepare the target compounds to investigate
their influence on herbicidal activity.
The 3-hydrazono compounds (7a–e) were synthesized
by the condensation of 5-isobutyl-3-acetyl-4-hydroxy-1H-
pyrrol-2(5H)-one (6) with the corresponding hydrazides
(Scheme 2). Compound 6 [18] was prepared from leucine
methyl ester hydrochloride and diketene using similar
strategy as compound 3. It was reported that when alkyla-
mines reacting with compound 6, the alkylamines were
definitely to condense with the carbonyl of the 3-acetyl
group rather than at the carbonyl at the 4-position [6]; thus,
hydrazides were speculated to condense with compound 6
in the same way. Furthermore, compounds 7 have multiple
Herein, we report the synthesis and bioactivities of
these compounds, and the preliminary structure-herbicidal
activity relationships are discussed.
Scheme 1. Synthesis of compounds 4a–e.
RESULT AND DISCUSSION
Synthesis.
The 3-hydrazido compounds (4a–e) were
synthesized from leucine methyl ester hydrochloride (1) in
three steps (Scheme 1). Compound 1 reacted with
monomalonate in the presence of 1-[3-(dimethylamino)
propyl]-3-ethylcarbodiimide hydrochloride, triethyl amine,
and catalytic amount of DMAP to give amidation product
(
2), which was treated with sodium methoxide via a
Dieckmann cyclization to afford methyl 2,5-dihydro-4-
hydroxy-5-isobutyl-2-oxo-1H-pyrrole-3-carboxylate (3)
14,15]. Because the carboxylate of 3 at the 3-position was
[
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August 2014
3-Hydrazido and 3-Hydrazono Derivatives of Tenuazonic Acid
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Scheme 2. Synthesis of compounds 7a–e.
a motility of 60% against oriental armyworm by using
dip-leaf method at a concentration of 600 mg/kg.
In summary, 3-hydrazido and 3-hydrazono-pyrrolidine-
2
,4-dione compounds were designed and synthesized to
investigate the influence of group at 3-position of pyrroli-
dine-2,4-dione on the bioactivity including herbicidal
activity. The 3-hydrazido (4) and the hydrazono compounds
(7) also showed herbicidal activity, especially against
dicotyledonous species amaranth pigweed, which pointed a
specific direction for further investigation.
tautomers, of which the enamine form drawn in Scheme 2
would be the most likely form according to similar
structures [6,20].
EXPERIMENTAL
1
Instruments.
H-NMR spectra were obtained using a
Bruker AV400 spectrometer (Swizerland) or a Varian Mercury
Plus 400 spectrometer (US) in CDCl3 or d6-DMSO solution
with TMS as the internal standard. Chemical shift values (d) are
given in parts per million. Elemental analyses were determined
on an Elementar vario EL CUBE elemental analyzer
Germany). HRMS data were obtained on a Ionspec 7.0T
Fourier transform ion cyclotron resonance mass spectrometer
FTICR MS) instrument (US). Microwave-assisted syntheses
were carried out with CEM Discover-S Microwave Synthesizer
US). The melting points were determined on an X-4 binocular
microscope melting point apparatus (Beijing Technical
Instruments Co., Beijing, China) and were uncorrected. All of
the anhydrous solvents were dried and distilled by using
standard techniques. TeA was prepared according published
procedure, and the structure and purity was assured by
comparing with literature [14–16].
Herbicidal activity.
Comparing with TeA, the 3-
hydrazido compounds (4a–e) gave relatively better herbicidal
activities; especially N-arylcarbonyl compounds 4b and 4c
gave 55% of herbicidal inhibition against the amaranth
pigweed, higher than the hydrophilic N-acetyl compound
(
(4a), the N-t-butoxycarbonyl compound (4e), and N-
(
ethoxycarbonyl compound (4d). The 3-hydrazono
compounds (7a–e) showed better herbicidal activity against
both dicotyledonous species rape and amaranth pigweed,
but the structure-activity relationships were opposite to
those observed for the compounds 4a–e. The compounds
(
7
b and 7c, with arylcarbonyl groups on the nitrogen,
gave weaker activity than N-acetyl compound (7a) and
the N-alkoxycarbonyl compounds 7e and 7d (the
herbicidal activities above 45% in Table 1 are showed in
bold style). However, all the target compounds did not
exhibit any herbicidal activity against monocot weeds,
thus showed obvious herbicidal selectivity.
The compounds were also tested the fungicidal, insecti-
cidal, and acaricidal activities; but most of them did not
exhibit much such activities, only compound 7b showed
Methyl 2-(3-ethoxy-3-oxopropanamido)-4-methylpentanoate
2). To a stirred solution of L-leucine methyl ester hydrochloride
18.07 g, 100 mmol) in dichloromethane (200 mL) at 0 C was
(
(
ꢀ
successively added triethylamine (10.12 g, 100 mmol), monomethyl
malonate (13.2 g, 100 mmol) and 1-[3-(dimethylamino)propyl]-
3-ethylcarbodiimide hydrochloride (20.13 g, 105 mmol). The mixture
was stirred over night at RT, then washed with 1M hydrochloric
acid and brine, dried over anhydrous sodium sulfate, and
evaporated to give compound 2 (20.13 g, 78.4%) as colorless oil.
Synthesis of methyl 2,5-dihydro-4-hydroxy-5-isobutyl-2-oxo-1H-
pyrrole-3-carboxlate (3). Metal sodium (0.26 g, 11.47 mmol)
was added to anhydrous methanol (10 mL). After sodium
disappeared, compound 2 (3.50 g, 13.50 mmol) was added, and
the mixture was refluxed for 1.5 h and then was concentrated.
The resulting solid was dissolved in water and washed with
dichloromethane. Then, the aqueous solution was acidified with
Table 1
Herbicidal activity of synthesized compounds (1.5 kg/ha, percent
inhibition).
Postemergence treatment (1.5 kg/ha)
Amaranth
pigweed
Barnyard
grass
Hairy
crabgrass
2
M HCl and extracted with ethyl acetate, washed with brine,
dried over anhydrous sodium sulfate, filtered, and concentrated
in vacuo. The residue was recrystallized from ethyl acetate to give
Compounds
Rape
TeA
10
15
15
5
20
10
50
30
35
25
20
0
25
55
55
25
35
55
0
20
10
0
10
0
5
15
5
0
0
10
0
0
0
0
30
0
0
0
ꢀ
compound 3 (1.23 g, 64.8%) as a white solid. mp 98–100 C
4
4
4
4
4
7
7
7
7
7
a
b
c
d
e
a
b
c
d
e
ꢀ
1
(
(
(
lit. [17] 98–101 C). H-NMR (400 MHz, CDCl
d, J= 6.0 Hz, 6H, CH(CH ), 1.45–1.53 (m, 1H, CH CH), 1.71–1.85
m, 2H, CH CH+ CH(CH ) ), 3.93 (s, 3H, OCH ), 4.18–4.21
3
) d 0.99
3
)
2
2
2
3 2
3
(m, 1H, CHNH), 5.77 (br, 1H, NH).
2,5-Dihydro-4-hydroxy-5-isobutyl-2-oxo-1H-pyrrole-3-
carbohydrazides (4). A substituted hydrazide (5.0 mmol) and
several drops of acetic acid were added to a solution of compound
(1.07g, 5.0 mmol) in THF (20 mL), and the mixture was stirred
at 100 C for 15min with microwave heating at 100 W. The
25
50
45
15
10
0
3
ꢀ
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Y-X. Liu, Z-P. Cui, Y-H. Li, Y-C. Gu, and Q-M. Wang
Vol 51
reaction mixture was then concentrated, the residue was dissolved
in EtOAc and washed with diluted hydrochloric acid then
brine, dried over anhydrous sodium sulfate, evaporated, and
recrystallized in ethyl acetate to give compound 4.
2
+ CH
2
CH), 2.28 (s, 3H, COCH
3
), 3.46 (s, 2H, COCH
),
2
3.74 (s, 3H, COOCH
(d, J = 6.4 Hz, 1H, NH)
Synthesis of 5-isobutyl-3-acetyl-4-hydroxy-1H-pyrrol-2(5H)-
one (6). To a methanol solution of sodium methoxide (sodium
78 mg, 3.4 mmol) in 10 mL dry methanol) was added a solution of
5 (0.92 g, 4.0 mmol) in dry methanol. The mixture was heated under
reflux for 1 h and then concentrated. The residue was diluted with
ice water and extracted twice with dichloromethane. The aqueous
layer was then carefully acidified with 2M hydrochloric acid in ice
bath and then extracted three times with dichloromethane. The
combined organic extracts were dried over anhydrous sodium
sulfate, filtered, and concentrated in vacuo. The residue was
recrystallized from petroleum and ethyl acetate to give compound 6
), 4.59–4.62 (m, 1H, CHNH), 7.33
3
0
Data for N -acetyl-2,5-dihydro-4-hydroxy-5-isobutyl-2-oxo-
(
1
H-pyrrole-3-carbohydrazide (4a).
Yield, 50.6%. White
ꢀ
1
solid; mp 175–177 C. H-NMR (400 MHz, DMSO-d ) d 0.88 (d,
6
J= 6.8 Hz, 6H, CH(CH
m, 1H, CH(CH ), 1.84 + 1.93 + 2.08 (s, 0.36 + 1.06 + 1.61 = 3H,
COCH ), 3.02 (br, 2H, NHNH), 3.99–4.23 (m, 1H, CHNH),
3 2 2
) ), 1.36–1.52 (m, 2H, CH CH), 1.72–1.84
(
3 2
)
3
8
.34 + 8.38 + 8.47 (br s, 0.54 + 0.36 + 0.07 = 1H, NH),
9
.75 + 10.06 + 10.19 (br s, 0.54 + 0.36 + 0.07 = 1H, OH). HRMS
ꢁ
for C11
H
16
N
0
3
O
4
(M ꢁ H) : 254.1146. Found: 254.1140.
Data for N -benzoyl-2,5-dihydro-4-hydroxy-5-isobutyl-2-oxo-
H-pyrrole-3-carbohydrazide (4b).
ꢀ
as a white solid (0.49 g, 70.3%). mp 108–111 C (lit. [18], 133–
ꢀ
1
1
Yield, 45.3%. White solid;
mp 202–204 C. H-NMR (400 MHz, DMSO-d ) d 0.92 (d,
J = 6.4 Hz, 6H, CH(CH ), 1.23–1.32 (m, 1H, CH CH), 1.63–
.70 (m, 1H, CH CH), 1.78–1.88 (m, 1H, CH(CH ), 3.99–4.05
m, 1H, CHNH), 4.48 (s, 1H, NH), 7.31 (br, 1H, NH), 7.50 (t,
1
1
3
34 C), H-NMR (400 MHz, CDCl ) d 0.97 (br, 6H, CH(CH ) ),
3
3 2
ꢀ
1
6
.42–1.50 (m, 1H, CH(CH
H, COCH
General procedure for the synthesis of compounds (7). To
a stirred EtOH solution of 6 (5mmol) was added a hydrazide
(5mmol), and the reaction mixture was heated under reflux for
2 h. After cooling, it was concentrated, and the residue was
dissolved in EtOAc and washed successively with dilute
hydrochloric acid and then brine, dried over anhydrous sodium
sulfate, evaporated, and recrystallized to give the compounds (7).
)
), 1.70–1.80 (m, 2H, CH
2
CH), 2.46 (s,
3
2
)
3 2
2
3
), 3.86 (d, J=10.0Hz, 1H, CHNH), 6.49 (br, 1H, NH).
1
(
2
3 2
)
J = 7.2 Hz, 2H, ArH), 7.58 (t, J = 7.2, 1H, ArH), 7.87 (d,
J = 7.2 Hz, 2H, ArH), 8.75 (br, 1H, NH), 10.50 (br, 1H, OH).
ꢁ
HRMS for C16
H
N O
18 3 4
(M ꢁ H) : 316.1303. Found: 316.1300.
0
Data for 2,5-dihydro-4-hydroxy-N -(4-nitrobenzoyl)-5-isobutyl-
2
-oxo-1H-pyrrole-3-carbohydrazide (4c).
Yield, 48.1%.
White solid; mp 149–152 C. H-NMR (400MHz, DMSO-d ) d
CH),
.63–1.70 (m, 1H, CH CH), 1.76–1.90 (m, 1H, CH(CH ) ),
ꢀ
1
0
Data for N -(1-(5-isobutyl-2,4-dioxopyrrolidin-3-ylidene)
ethyl)acetohydrazide (7a).
168–169 C. H-NMR (400 MHz, CD OD) d 0.95–0.98 (m, 6H,
6
0
1
4
.92 (d, J = 6.8 Hz, 6H, CH(CH
3 2
) ), 1.25–1.32 (m, 1H, CH
2
Yield, 69.7%. White solid; mp
ꢀ
1
2
3 2
3
.02–4.07 (m, 1H, CHNH), 4.56 (br, 1H, NH), 7.36 (br, 1H,
CH(CH
CH CH), 1.78–1.90 (m, 1H, CH(CH
2.48 + 2.52 (s, 3H, CCH ), 3.76–3.85 (m, 1H, CHNH). HRMS
3
)
2
), 1.36–1.45 (m, 1H, CH
2
CH), 1.57–1.67 (m, 1H,
NH), 8.10 (d, J = 8.8Hz, 2H, ArH), 8.35 (d, J = 8.8 Hz, 2H, ArH),
.86 (br, 1H, NH), 10.84 (br, 1H, OH). HRMS for C H N O (M
2
3
)
2
), 2.08 (s, 3H, COCH ),
3
8
3
1
6 17 4 6
ꢁ
ꢁ
H) : 361.1154. Found: 361.1149.
Data for 2,5-dihydro-N -ethoxycarbonyl-4-hydroxy-5-isobutyl-
for C12
H
N
18
3
O
3
(M ꢁ H) : 252.1454. Found: 252.1357.
0
0
Data for N -(1-(5-isobutyl-2,4-dioxopyrrolidin-3-ylidene)
2
-oxo-1H-pyrrole-3-carbohydrazide (4d).
Yield, 63.2%.
ethyl)benzohydrazide (7b).
Yield, 56.3%. White solid;
OD) d 0.97–1.00
), 1.40–1.47 (m, 1H, CH(CH ), 1.61–
1.69 (m, 1H, CH CH), 1.81–1.91 (m, 1H, CH CH),
2.55 + 2.59 (s, 3H, CCH ), 3.79–3.89 (m, 1H, CHNH), 7.55
ꢀ
1
ꢀ
1
White solid; mp 204–205 C. H-NMR (400MHz, DMSO-d ) d
mp 188–190 C. H-NMR (400 MHz, CD
3
6
0
.88 (d, J = 6.0 Hz, 6H, CH(CH ) ), 1.22 (t, J = 5.4 Hz, 3H,
(m, 6H, CH(CH
3
)
2
)
3 2
3
2
CH
2 3 2
CH ), 1.35–1.49 (m, 2H, CH CH), 1.73–1.84 (m, 1H, CH
2
2
(
CH
3 2
) ), 3.00 (s, 1H, NH), 3.42 (br, 1H, NH), 4.02–4.17 (m, 3H,
3
CH
for C12
2
CH
H
3
+ CHNH), 8.33 (br, 1H, NH), 9.90 (br, 1H, OH). HRMS
(t, J = 7.6 Hz, 2H, ArH), 7.65 (t, J = 7.6 Hz, 1H, ArH), 7.93
ꢁ
ꢁ
(
3
d, J = 7.6 Hz, 2H, ArH). HRMS for C H N O (M ꢁ H) :
N O
18 3 5
(Mꢁ H) : 284.1252. Found: 284.1255.
17 20 3 3
0
14.1510. Found: 314.1515.
Data for N -(tert-butoxycarbonyl)-2,5-dihydro-4-hydroxy-5-
0
Data for N -(1-(5-isobutyl-2,4-dioxopyrrolidin-3-ylidene)
isobutyl-2-oxo-1H-pyrrole-3-carbohydrazide (4e).
Yield,
7.7%. White solid; mp 159–161 C. H-NMR (400 MHz, DMSO-
) d 0.87–0.92 (m, 6H, CH(CH ), 1.24–1.34 (m, 1H, CH CH),
.41 (s, 9H, (CH ), 1.52–1.59 (m, 1H, CH CH), 1.75–1.85 (m,
H, CH(CH ) ), 4.06–4.16 (m, 1H, CHNH), 5.22 (br, 1H, NH),
ꢀ
1
ethyl)-4-nitrobenzohydrazide (7c).
Yield, 67.6%. White
6
ꢀ
1
solid; mp 225 C. H-NMR (400 MHz, CD OD) d 0.97–1.00
d
1
1
8
6
3
)
2
2
3
(
(
(
m, 6H, CH(CH ) ), 1.40–1.47 (m, 1H, CH(CH ) ), 1.59–1.71
)
3
2
3 2 3 2
3
m, 1H, CH
2
CH), 1.81–1.92 (m, 1H, CH
2
CH), 2.58 + 2.61
3
2
3
s, 3H, N═CCH ), 3.80–3.90 (m, 1H, CHNH), 8.15 (d, J=8.4Hz,
.34 (br, 1H, NH), 8.88 (br, 1H, NH), 9.33 (br, 1H, OH). HRMS
ꢁ
2H, ArH), 8.41 (d, J = 8.4 Hz, 2H, ArH). HRMS for C H N O
1
7
19
4
5
for C14
H
22
N O
3 5
(M ꢁ H) : 312.1565. Found: 312.1561.
ꢁ
(
Mꢁ H) : 359.1361. Found: 359.1362.
Synthesis of N-acetoacetyl leucine methyl ester (5). To a
0
Data for ethyl N -(1-(5-isobutyl-2,4-dioxopyrrolidin-3-yli-
stirred solution of leucine methyl ester hydrochloride (3.67 g,
ꢀ
dene)ethyl)-hydrazinecarboxylate (7d).
Yield, 53.6%.
2
0 mmol) in dichloromethane (30 mL) at 0 C, a solution of
ꢀ
1
White solid; mp 147–149 C. H-NMR (400 MHz, CD OD)
triethylamine (2.12 g, 21 mmol) in dichloromethane (10 mL) was
added. Diketene 1.80 g (21 mmol) in dichloromethane (15 mL)
was added dropwise, and then the reaction was stirred in an ice
bath over night. Water was added to the reaction mixture, and
then the organic layer was separated, washed twice with water,
dried over anhydrous sodium sulfate, filtrated, and concentrated
in vacuo. The crude residue was purified by flash column
3
d 0.95–0.98 (m, 6H, CH(CH ) ), 1.31 (t, 3H, J = 7.2 Hz, CH CH ),
3 2
2
3
1
1
1
.36–1.44 (m, 1H, CH(CH
.89 (m, 1H, CH CH), 2.49 + 2.52 (s, 3H, N═CCH
H, CHNH), 4.23 (q, J = 7.2 Hz, 2H, OCH
3 2 2
) ), 1.58–1.66 (m,1H, CH CH), 1.78–
2
3
), 3.80 (m,
2
). HRMS for
+
C H N O (M+ Na) : 306.1424. Found: 306.1423.
Data for tert-butyl N -(1-(5-isobutyl-2,4-dioxopyrrolidin-3-
13 20
3 4
0
chromatography (petroleum–ethyl acetate = 2:1) to give 5 as a
ylidene)ethyl)-hydrazinecarboxylate (7e).
Yield, 52.7%.
1
ꢀ
1
colorless oil (4.35 g, yield 86.5%). H-NMR (400 MHz, CDCl )
White solid; mp 159–161 C. H-NMR (400 MHz, CD OD) d
3
3
d 0.95 (br, 6H, CH(CH
)
3 2
), 1.57–1.70 (m, 3H, CH(CH
3
)
0.95–0.98 (m, 6H, CH(CH ) ), 1.36–1.43 (m, 1H, CH(CH ) ),
3
2
3 2
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1
.52 (s, 9H, C(CH) ), 1.58–1.67 (m, 1H, CH CH), 1.77–1.89
REFERENCES AND NOTES
3
2
(
(
m, 1H, CH CH), 2.49 + 2.52 (s, 3H, N═CHCH ), 3.75–3.84
2
3
ꢁ
[1] Rosett, T.; Sankhala, R. H.; Stickings, C. E.; Taylor, M. E. U.;
Thomas, R. Biochem J 1957, 67, 390.
m, 1H, CHNH). HRMS for C15H N O
25 3 4
(Mꢁ H) : 310.1772.
Found: 310.1779.
[
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Acknowledgments. This work was supported by the National Key
Project for Basic Research (2010CB126106) and the National
Natural Science Foundation of China (20972080) and the Syngenta
PhD (postgraduate) Program and the National Key Technology
Research and Development Program (2011BAE06B05). We thank
China Agricultural University to supply some of chemical reagents
and the National Key Technology Research and Development
Program (2012BAK25B03-3).
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet