Synthesis of potential fungicides based on N-(3-furanyl)pyrrolecarboxamides and N-(3-furanyl)pyrazolecarboxamides

Article abstract of DOI:10.1007/s00706-009-0187-6

An efficient synthesis of novel N-(3-furanyl)pyrrolecarboxamides and N-(3-furanyl)pyrazolecarboxamides is presented starting from furan-3-carboxylic acid. Two complementary strategies to 2-aryl-3-furanamines with directed ortho lithiation, functionalizati

Full text of DOI:10.1007/s00706-009-0187-6

Monatsh Chem (2009) 140:1349–1359
DOI 10.1007/s00706-009-0187-6
ORIGINAL PAPER
Synthesis of potential fungicides based
on N-(3-furanyl)pyrrolecarboxamides
and N-(3-furanyl)pyrazolecarboxamides
Krzysztof Kolodziejczyk Æ Gheorghe D. Roiban Æ
Michael Schnu¨rch Æ Marko D. Mihovilovic Æ
Peter Stanetty
Received: 31 March 2009 / Accepted: 2 September 2009 / Published online: 19 September 2009
Ó Springer-Verlag 2009
Abstract An efficient synthesis of novel N-(3-furanyl)pyr-
rolecarboxamides and N-(3-furanyl)pyrazolecarboxamides is
presented starting from furan-3-carboxylic acid. Two com-
plementary strategies to 2-aryl-3-furanamines with directed
ortho lithiation, functionalization of the 2-position, and sub-
sequent cross-coupling reaction as key steps were developed.
Acylation of these intermediates with appropriate acid chlo-
rides led finally to the target compounds.
identify the required motifs for the unique biological
properties. The presence of the 5,6-dihydro-1,4-oxathiine
ring in carboxin proved not to be an essential part of the
fungicide, because its replacement by other rings did not
result in loss of the systemic fungicidal activity [4].
The replacement of sulfur in carboxin by a CH2 group
allowed the discovery of other new fungicides. Pyrocar-
bolid (Sicarol, III) [5]––active against smuts and rusts––
had higher phytotoxicity than carboxin. Mebenil (Basfun-
gin, IV) [6], patented as a systemic fungicide, is a simple
aromatic compound which contains the anilide moiety
common to many systemic fungicides. Huppatz et al. [7]
obtained a patent for new 4-pyrazolecarboxamide and
5-pyrazolecarboxamide derivatives V (Fig. 1), which
proved to be active ingredients in combatting plant fungal
diseases. A similar substitution pattern for pyrazolecarb-
oxamides was introduced by Monsanto in 1992 and 1993
when 3-difluoromethylpyrazolecarboxamide derivatives
[8] and pyrazolecarboxanilide derivatives [9] with fungi-
cidal activity were synthesized. Syngenta also obtained
patents in the pyrrole series for trifluoromethylpyrrole-
carboxamide VI (Fig. 1) [10–12].
Keywords ortho Lithiation ꢀ Fungicides ꢀ
Organometallic compounds ꢀ Heterocycles ꢀ
Suzuki reaction
Introduction
Carboxin (Vitavax, I) and its S,S-dioxide, oxycarboxin [1]
(Plantvax, II) are well established systemic fungicides and
used worldwide as active components of many plant-pro-
tecting agents to control crop smuts and rust diseases
(Fig. 1) [2, 3].
After initial reports in the mid 1960s elaborate modifi-
cations of the carboxin lead structure were carried out to
Our interest for the synthesis of carboxamide 1 (Fig. 2)
was triggered by our previous research on developing
metallation-based strategies for modification of the furan
core with various substituents. In a recent communication
[13] we reported the synthesis of new 2-substituted N-Boc-
3-furanamines via directed lithiation of N-Boc-3-furan-
amine followed by quenching of the lithiated intermediate
with electrophiles. The halogen derivatives obtained were
further subjected to cross-coupling reactions with (substi-
tuted) phenylboronic acids leading to new 2-phenyl-N-Boc-
3-furanamines. This strategy was a short and efficient
means of preparation of target compounds of the general
type 1.
K. Kolodziejczyk ꢀ M. Schnu
¨rch (&) ꢀ M. D. Mihovilovic ꢀ
P. Stanetty
Institute of Applied Synthetic Chemistry,
Vienna University of Technology, Getreidemarkt 9/163-OC,
1060 Vienna, Austria
e-mail: mschnuerch@ioc.tuwien.ac.at
G. D. Roiban
Faculty of Chemistry and Chemical Engineering,
Babes-Bolyai University, 11 Arany Janos Street,
400028 Cluj-Napoca, Romania
123

1350
K. Kolodziejczyk et al.
Fig. 1
O
S
O
S
O
H
H
H
N
N
N
O
O
O
O
O
Pyrocarbolid, Sicarol®
Carboxin, Vitavax®
Oxycarboxin, Plantvax®
I
II
III
F3C
N
O
R4
N
R1
NH
H
H
N
N
R2
N
O
R3
O
R5
Mebenil, Basfungin®, BASF
5-Pyrazolecarboxamides
Trifluoromethylpyrrole
carboxamide
IV
V
VI
R1, R4 = H, Halogen, Alkyl, NH2, CN; R2 = Aryl; R3= H, Alkyl, Aryl,
Alkenyl
Synthesis of 2-aryl-3-furanamines
Y
F3C
N
H
N
The synthetic strategy for key intermediates 9a–9c is out-
lined in Scheme 1.
O
In the first strategy (pathway A) the carboxylic acid 2
was first transformed into the N-Boc-3-furanamine (3) by a
Curtius rearrangement. A notable improvement of the yield
from 54% [14] to over 74% was achieved when using
milder reaction conditions. The O-t-butylcarbamate 3
obtained was subjected to directed ortho lithiation opening
the way to functionalization of the 2-position. To investi-
gate the scope and limitations of this lithiation-based
functionalization of compound 3 we prepared a number of
2,3-disubstituted furans 4a–4k. The results are summarized
in Table 1 (entries 1–11).
O
R5
Trifluoromethylpyrrole
carboxamide
1
R5= H, Cl, F; Y=CH, N
Fig. 2
The ortho lithiation was carried out using 2.5 equiv. t-
BuLi in the presence of TMEDA [13, 17]. In a first set of
experiments the lithiated intermediate was quenched with
several carbonyl-containing electrophiles. Ethyl chloro-
formate and t-butylisocyanate (entries 1 and 2) were used
as electrophiles for the preparation of the corresponding
ester 4a and amide 4b in excellent yields (91% in both
cases). Reaction with DMF (entry 3) enabled introduction
of the aldehyde functionality (4c, 51%) whereas cyclo-
hexanone as electrophile led to the corresponding
cyclohexanol derivative 4d (entry 4) in excellent yield
(96%). Surprising results were obtained when aromatic
aldehydes were used as electrophiles (entries 5 and 6):
Results and discussion
Based on retrosynthetic rationale, two strategies
a
towards 2-aryl-3-furanamines 9a–9c as key intermediates
for the synthesis of the target molecules are outlined
(Scheme 1). Both routes start from furan-3-carboxylic
acid (2) and take advantage of a Curtius rearrangement
[14, 15], directed ortho metallation (DoM) [16], and
cross-coupling reactions but differ in the order of the
steps. When the required substitution pattern is estab-
lished, formation of the target compounds from the
amide should be straightforward.
123

Synthesis of potential fungicides
1351
(HO)2B
R2
NHBoc
R1
NHBoc
ii) iii)
5a-5c
O
51-96%
O
iv)
i)
4a 4k
-
3
74%
NHBoc
NH2
53-72%
Pathway A
v)
COOH
O
O
O
61-90%
R2
R2
6a 6c
-
9a 9c
-
iia)
iii)
2
i)
41-89%
Pathway B
iv)
68-75%
COOH
COOH
R1
O
O
7a 7c
50-91%
R2
-
(HO)2B
8a 8c
-
R2
5a-5c
Reagents and conditions: i) DPPA, t-BuOH, Et3N, Toluene; ii) t-BuLi,
TMEDA, THF; iia) LDA, THF; -80 °C to -30 °C; iii) Electrophile, THF;
iv) ArB(OH)2, K2CO3, Pd(PPh3)4, THF; v) TFA, CH2Cl2.
Scheme 1
Table 1 Synthesis of
Entry Starting material Reactant
Pathway Product R1
Yield (%)
91
2-substituted N-Boc-3-
furanamines and 2-substituted
furan-3-carboxylic acids
1
3
3
3
3
3
3
3
3
3
3
3
2
2
2
2
ClCOOEt
A
A
A
A
A
A
A
A
A
A
A
B
B
B
B
4a
4b
4c
4d
4e
4f
COOEt
2
t-BuNCO
CONH-t-Bu 91
3
DMF
CHO
C6H10OH
PhCO
ClPhCO
Cl
51
4
Cyclohexanone
96
5
Benzaldehyde
56
6
p-Chlorobenzaldehyde
62
7
Hexachloroethane
4g
4h
4i
65
8
1,2-Dibromotetrachloroethane
Br
96
53–72a
9
I2
I
10
11
12
13
14
15
ClSiMe3
MeI
4j
SiMe3
Me
52
4k
7a
7b
7b
7c
96
I2
I
57
B(OMe)3
B(O-i-Pr)3
ClSnBu3
B(OH)2
B(OH)2
SnBu3
67
a
Overall yield determined after
subsequent Suzuki–Miyaura
coupling reaction
41
89
instead of the expected alcohols the ketones 4e (56%) and
4f (62%) were obtained almost exclusively. There is pre-
cedence in the literature on the thiophene series for such
oxidation to occur upon work-up [18]. In particular, aerial
oxidation was used in combination with lithiation strategies
in related fused homoaromatic and heteroaromatic systems
[19–22]. In addition, a stabilizing effect of carbonyl groups
adjacent to the N-Boc group has been reported previously
[23].
For the target oriented approach, halogenated com-
pounds 4g–4i (entries 7–9) were envisaged for subsequent
cross-coupling chemistry. The products were obtained by
using different halogen donors, for example hexachloro-
ethane, 1,2-dibromotetrachloroethane, or I2 at -80 °C. It
123

1352
K. Kolodziejczyk et al.
should be mentioned that compounds 4g–4i were of limited
stability. Products 4g (65%) and 4h (96%) were beige
solids which tended to darken and decompose on storage at
room temperature or even in the refrigerator. Iodo deriva-
tive 4i (entry 9) proved to be particularly unstable.
Although transparent pale yellow in solution, after removal
of the solvent the product decomposed within minutes at
room temperature in an exothermic reaction. Because of its
instability we avoided isolation and purification of com-
pound 4i, therefore only yields after the cross-coupling
reaction could be determined (53–72% for compounds
6a–6c, starting from 3, over two steps). When TMS chloride
was used as electrophile the silyl species 4j (entry 10) was
obtained in 52% yield; introduction of a methyl group was
successfully accomplished with methyl iodide (4k, 96%).
The halide 4i was now used directly in solution for the
Suzuki–Miyaura cross-coupling procedure, chloride 4g and
bromide 4h not being investigated for further coupling
reactions because of their lower reactivity in such trans-
formations. The Boc-protected amine 4i was submitted to
the cross-coupling procedure using phenylboronic acids
5a–5c to yield derivatives 6a–6c [13], as summarized in
Table 2.
the a-protons of the heterocyclic ring is higher than that of
phenyl protons, directed ortho metallation (DoM) can be
achieved. Knight [27, 28] was the first to report that furan-
3-carboxylic acid (2) can be regioselectively lithiated with
2 equiv. LDA exclusively at the 2-position in THF at
-78 °C. Lithiated compound 2 was subsequently quenched
with EtI, acetone, benzaldehyde, benzophenone, citral [28],
and a number of different aromatic aldehydes [29]. On the
other hand, Shuyuan [30] reported use of even n-BuLi as
base, methylating the furan-3-carboxylic acid system at
C-2 with MeI as electrophile in THF. Having in mind our
target compounds we were particularly interested in
introducing electrophiles (I, B(OH)2, SnR3) that would
allow subsequent cross-coupling reactions. These results
are provided in Table 1 (entries 12–15).
Takahashi et al. [31] reported synthesis of the iodo
derivative 7a, but no details of yield or analytical data of
the product were published. By using LDA as base at
-80 °C compound 7a was obtained in 57% yield. In
contrast with the iodo derivative 4i, which decomposed on
storage and after solvent evaporation, 2-iodofuran-3-car-
boxylic acid (7a) is very stable and easy to handle. For
synthesis of 7b, both B(OMe)3 and B(O-iPr)3 were used as
electrophiles. It was found that better yields (67%) were
obtained by use of B(OMe)3 than by use of B(O-iPr)3
(41%). The tributyltin derivative 7c was obtained in high
yield of 89% by using ClSnBu3 as electrophile, although
the separation of tributyltin impurities from the product
was tedious and required careful column chromatography.
Subsequently, the iodo derivative 7a was cross-coupled
with boronic acids 5a–5c to provide compounds 8a–8c. In
this case, yields of all three boronic acids ranged from 50 to
91% (Table 3).
The best yield was obtained using simple phenylboronic
acid (6a, 68%) and 4-fluorophenylboronic acid (6c, 72%)
as coupling partner. With 4-chlorophenylboronic acid the
yield was somewhat lower (6b, 53%).
As an alternative we also attempted reaction of the
lithiated species of 3 with trimethylborate, triisopropyl-
borate, tributyltin chloride, and trimethyltin chloride, in
order to obtain a metallated species for subsequent cou-
pling reactions with aryl halides. However, the expected
organometallic compounds could not be obtained. Still,
via route A the desired compounds 6a–6c were obtained in
39–53% yield over three steps.
Additionally, products 8a–8c were very simple to isolate
from the reaction mixture by precipitation and crystalli-
zation. This was not possible with products 6a–6c, so
column chromatography was required in the purification
step in all cases for pathway A.
The second route (pathway B) was established by using
the ortho-directing ability of the carboxyl group for
functionalization and cross-coupling of the 2-position.
Subsequent Curtius rearrangement of the carboxylic
derivatives towards Boc-protected amines is a convergent
strategy for obtaining compounds 6a–6c. It is generally
recognized that the carboxylic acid moiety is not a useful
directed metallation group (DMG) when butyllithium is
employed as base [16, 24–26]. But, because the acidity of
Other possibilities were examined for the coupling
reaction by reacting compound 7b with 1-bromo-4-chlo-
robenzene. Unfortunately, the expected coupling product
was not formed and the only product isolated from the
reaction mixture was furan-3-carboxylic acid, proving that
the 2-boronofuran-3-carboxylic acid undergoes easy pro-
todeboronation under the reaction conditions.
Table 2 Synthesis of 2-substituted N-Boc-3-furanamines 6a–6c
Table 3 Synthesis of 2-substituted furan-3-carboxylic acids 8a–8c
Entry Starting Reactant R2 Pathway Product Yield (%)
material
Entry Starting material Reactant R2 Pathway Product Yield (%)
1
2
3
7a
7a
7a
5a
5b
5c
H
Cl
F
B
B
B
8a
8b
8c
91
50
50
1
2
3
4i
4i
4i
5a
5b
5c
H
Cl
F
A
A
A
6a
6b
6c
68
53
72
123

Synthesis of potential fungicides
1353
Table 4 Synthesis of 2-substituted N-Boc-3-furanamines 6a–6c by Curtius rearrangement and further deprotection to 9a–9c
Entry
Starting material
R2
Product
Yield (%)
Deprotection product
Yield (%)
1
2
3
8a
8a
8a
H
Cl
F
6a
6b
6c
68
74
75
9a
9b
9c
61
90
81
Scheme 2
NH2
O
R2
Y
N
9a 9c
-
F3C
CF3
CF3
H
N
i)
ii)
HOOC
ClOC
Y
N
Y
N
O
100%
26-67%
O
R2
10a-10b
11a-11b
1a 1f
-
Reagents and conditions: i) PCl5, Et2O, r.t., 2 - 4 h; ii) CH2Cl2, DMAP, r.t.,
23 - 40 h; Y = CH; R2 = H, 1a; R2=Cl, 1c; R2 = F, 1e; Y = N; R2 = H, 1b, R2
= Cl, 1d, R2 = F, 1f.
were synthesized by reaction of the corresponding pyrrol-
ecarboxylic acid or pyrazolecarboxylic acid 10a, 10b
(provided by Syngenta) with phosphorus pentachloride in
dry diethyl ether at room temperature (Scheme 2) [32].
Compounds 11a and 11b were obtained in quantitative
yield.
Table 5 Synthesis of trifluoromethylpyrrolecarboxamides
Carbonyl chloride
Y
Amine
R2
Product
Yield (%)
10a
10a
10a
10b
10b
10b
CH
CH
CH
N
9a
9b
9c
9a
9b
9c
H
Cl
F
1a
1b
1c
1d
1e
1f
38
53
53
26
35
67
H
Cl
F
Reaction of amines with acyl chlorides
N
N
The final step in the synthesis of the compounds 1a–1f
consisted of formation of the amide (Scheme 2).
In accordance with literature reports [33], DMAP was
used initially as catalyst. However, the results were not
satisfying as it can be seen for products 1a (38%) and 1d
(26%) (Table 5).
Subsequent Curtius rearrangement of 2-aryl-3-furan-
carboxylic acids 8a–8c led to the corresponding protected
amines 6a–6c in acceptable yields (Table 4). When both
routes were compared the overall yields over three steps
were significantly higher in route A (39–53%) than in route
B (21–35%).
In order to increase the yield triethylamine was used as
base. The improvements were not impressive, but the
yields obtained for 1b and 1c were much better (53% in
both cases). Compound 1e was obtained in 35% yield
whereas 1f was prepared in 67% yield.
Deprotected 3-furanamines 9a–9c were obtained by
TFA-mediated carbamate cleavage under very mild con-
ditions. Stirring at room temperature for 6 h was usually
sufficient to complete the reaction (9a: 61%, 9b: 90%, 9c:
81%, Table 4).
Summary
Synthesis of acid chlorides
Synthesis of the target molecules 1a–1f was achieved in a
short sequence and in acceptable yields. Two different routes
towards the key intermediates 6a–6c were developed. Both
For the reaction with amines 9a–9c two different acid
chlorides were used. Acid chlorides 11a and 11b
123

1354
K. Kolodziejczyk et al.
the remaining solid was separated by decantation and dried
under reduced pressure (oil pump). The filtrate was
evaporated and triturated with 5 cm3 petroleum ether to
yield 0.7 g product 3 as a second fraction. N-(3-furyl)car-
bamic acid tert-butyl ester 3 (7.3 g, 40.0 mmol) was
routes take advantage of the same synthetic steps namely
DoM, Suzuki–Miyaura cross-coupling, and Curtius rear-
rangement, however, the order in which those steps were
performed differs. Route A proved to be the higher yielding
pathway. However, in route A the iodide 4i, required for
subsequent cross-coupling reactions, is very unstable and
cannot be isolated. This is not the case for route B, because
there are no problems with the stability of the corresponding
iodide 7a. Therefore, both routes have advantages and dis-
advantages and it depends on the specific problem which one
should be preferred. Generally, the Suzuki–Miyaura cross-
coupling reaction seemed to work better in route A. Amine
deprotection worked well in all cases. Overall, the chemistry
reported enables easy and fast access to the target com-
pounds 1a–1f as potential crop-protecting agents.
Additionally, the substrate scope of DoM of compound 3
was investigated and generally high yields were obtained.
However, yields dropped with increasing steric bulk of the
electrophile. Transmetallation of the lithiated intermediate
was not possible with substrate 3 but worked reasonably well
on starting material 2.
1
obtained as yellow crystals (74%); m.p.: 136–138 °C; H
NMR (CDCl3): d = 1.50 (s, 9H, C(CH3)3), 6.24 (bs, 1H,
NH), 6.27 (d, 1H, H4, 3J = 2 Hz), 7.26 (d, 1H, H5,
3J = 2.0 Hz), 7.68 (bs, 1H, H2) ppm; 13C NMR (CDCl3):
d = 28.3 (q, C(CH3)3), 80.5 (s, C(CH3)3), 104.7 (d, C4),
124.9 (s, C3), 130.6 (d, C2), 141.6 (d, C5), 152.8
(s, NHCO) ppm.
General procedure for preparation of compounds
4a–4k
To a cooled (-90 to -70 °C), stirred solution of compound
3 (1.64 mmol) and TMEDA (4.1 mmol) in 25 cm3 dry
THF under argon, a solution of t-BuLi in pentane (1.6 M,
4.1 mmol) was added dropwise. The mixture was then
stirred for 1–2 h while raising the temperature from -90 to
-40 °C. After addition of an electrophile (1.97 mmol; as a
solution in THF if solid) the reaction mixture was stirred
for 6 h and allowed to warm to room temperature over that
period. The reaction mixture was then quenched with
excess satd. NaHCO3 solution (40 cm3) and extracted with
CH2Cl2 (6 9 25 cm3). The combined organic layers were
dried over Na2SO4 and the solvent was evaporated at
400–500 mbar and 30–35 °C. The solution obtained was
then purified by filtration through a column of silica gel,
using CH2Cl2 as eluent. The first fractions containing the
desired product were collected and the solvent was evap-
orated under reduced pressure (30–35 °C, 400–500 mbar).
In the case of the unstable compound 4i the solvent was not
evaporated completely and only yields over two steps after
the subsequent Suzuki–Miyaura coupling reaction were
determined.
Experimental
Unless otherwise noted, chemicals were purchased from
commercial suppliers and used without further purification.
All solvents were distilled prior to use. Flash column
chromatography was performed on silica gel 60 from
Merck (40–63 lm). Melting points were determined using
a Kofler-type Leica Galen III micro hot-stage microscope.
NMR spectra were recorded from CDCl3 or DMSO-d6
solutions on a Bruker AC 200 (1H 200 MHz, 13C 50 MHz)
spectrometer and chemical shifts are reported in ppm using
TMS as internal standard.
N-(3-Furyl)carbamic acid 1,1-dimethylethyl ester
(3, C9H13NO3)
3-(1,1-Dimethylethoxycarbonylamino)furan-2-carboxylic
acid ethyl ester (4a, C12H17NO5)
To a solution of 6.0 g furan-3-carboxylic acid (2,
54.0 mmol) in 20 cm3 dry toluene 21 cm3 freshly dried
t-BuOH (0.216 mol), 14.1 cm3 diphenylphosphoryl azide
(DPPA, 65.0 mmol), and 9.0 cm3 dry triethylamine
(65.0 mmol) were added dropwise. The resulting solution
was stirred at room temperature for 1.5 h. The mixture was
then heated to 85–95 °C for 3 h. Most of the toluene was
evaporated and the brown, oily residue was dissolved in
70 cm3 ethyl acetate, and the solution was washed with
water (4 9 30 cm3) and then with satd. NaHCO3 solution
(4 9 30 cm3). The ethyl acetate solution was dried over
Na2SO4 and filtered. The solvent was removed by vacuum
evaporation at 50 °C to afford a brown solid. The crude
product was then triturated once with 15 cm3 DIPE, and
Yellow crystals (91%); m.p.: 47–49 °C ([1] 97%); 1H
3
NMR (CDCl3): d = 1.41 (t, 3H, CH2CH3, J = 7.0 Hz),
1.51 (s, 9H, C(CH3)3), 4.39 (q, 2H, CH2CH3, 3J = 7.0 Hz),
7.21 (bs, 1H, H4), 7.37 (dd, 1H, H5, 3J = 2.0 Hz,
5J = 0.4 Hz), 8.22 (bs, 1H, NH) ppm; 13C NMR (CDCl3):
d = 13.8 (q, CH2CH3), 27.6 (q, C(CH3)3), 60.1 (t,
CH2CH3), 80.7 (s, C(CH3)3), 105.7 (d, C4), 127.4 (s,
C3), 135.8 (s, C2), 144.9 (d, C5), 151.5 (s, NHCO), 159.7
(s, COOEt) ppm.
N-(2-(1,1-Dimethylethylaminocarbonyl)-3-furyl)carbamic
acid 1,1-dimethylethyl ester (4b, C14H22N2O4)
White crystals (91%); m.p.: 102–107 °C; 1H NMR
(CDCl3): d = 1.38 (s, 9H, CONHC(CH3)3), 1.42 (s, 9H,
123

Synthesis of potential fungicides
1355
NHCOOC(CH3)3), 5.85 (bs, 1H, CONHC(CH3)3), 7.08–
7.15 (bs, 1H, H4), 7.15 (s, 1H, H5), 8.60 (bs, 1H, NH) ppm;
13C NMR (CDCl3): d = 28.2 (q, CONHC(CH3)3), 29.1 (q,
NHCOOC(CH3)3), 51.4 (s, CONHC(CH3)3), 80.6 (s,
NHCOOC(CH3)3), 106.7 (d, C4), 130.6 (s, C3), 132.5 (s,
C2), 142.3 (d, C5), 152.5 (s, NHCO), 160.2 (s,
CONHC(CH3)3) ppm.
C(CH3)3), 80.5 (s, C(CH3)3), 108.8 (d, C4), 119.4 (s, C3),
139.7 (d, C5), 142.0 (s, C2), 153.9 (s, NHCO) ppm.
General procedure for preparation of compounds
6a–6c
Pathway A: To 150 cm3 of a dioxane–water mixture (4:1)
in a three-necked, round-bottomed flask equipped with a
condenser, thermometer, and argon inlet, a solution of 4i
(ca. 10.0 mmol) in THF was added. Boronic acids 5a–5c
(12.1 mmol) and K2CO3 (22.0 mmol) were added to the
system. The flask was flushed with argon and then
Pd(PPh3)4 (0.272 mmol, 2.2 mol%) was added. The reac-
tion mixture was heated to 70–80 °C keeping the inert
atmosphere until the TLC showed complete reaction (typ-
ically 24 h), then the obtained mixture was quenched with
40 cm3 satd. NaHCO3 solution, extracted with CH2Cl2
(4 9 100 cm3), and the combined organic layers were
dried over Na2SO4. After solvent evaporation the residue
was purified by flash column chromatography using
PE–EtOAc (10:1) as eluent. The products 6a–6c were
obtained in overall yield varying between 53 and 72%,
calculated on the basis of compound 3.
N-(2-Formyl-3-furyl)carbamic acid 1,1-dimethylethyl ester
(4c)
1
Pale yellow crystals (51%); m.p.: 58–61 °C; H NMR and
13C NMR spectra were identical with those described in
Ref. [13].
N-(2-(1-Hydroxycyclohexyl)-3-furyl)carbamic
acid 1,1-dimethylethyl ester (4d)
Colourless oil (96%); 1H NMR spectrum was identical with
that described in Ref. [13].
N-(2-Benzoyl-3-furyl)carbamic acid 1,1-dimethylethyl
ester (4e)
1
Pale yellow oil (56%); H NMR and 13C NMR spectra
were identical with those described in Ref. [13].
N-(2-(4-Chlorobenzoyl)-3-furyl)carbamic acid 1,1-dimeth-
ylethyl ester (4f)
Pathway B: 2-Arylfuran-3-carboxylic acids 8a–8c
(0.85 mmol) were dissolved in 12 cm3 dry toluene and
then dry triethylamine (1.02 mmol) was added. DPPA
(1.02 mmol) and freshly dried t-BuOH (10.2 mmol) were
added and the resulting solution was stirred at room tem-
perature for 1.5 h and then heated to 85–95 °C with
stirring. After 2 h, the toluene was removed under reduced
pressure. The residue, as a brown oil, was dissolved in
20 cm3 ethyl acetate and the solution was washed with
water (4 9 15 cm3). The ethyl acetate solution was dried
over Na2SO4 and filtered. The solvent was removed at
reduced pressure and the residue purified by flash column
chromatography (silica gel), using PE–EtOAc (10:1) as
eluent, to give products 6a–6c.
1
Colourless crystals (62%); m.p.: 52–55 °C; H NMR and
13C NMR spectra were identical with those described in
Ref. [13].
N-(2-Chloro-3-furyl)carbamic acid 1,1-dimethylethyl ester
(4g)
1
Beige solid (65%); H NMR and 13C NMR spectra were
identical with those described in Ref. [13].
N-(2-Bromo-3-furyl)carbamic acid 1,1-dimethylethyl ester
(4h)
1
Beige solid (96%); H NMR spectrum was identical with
that described in Ref. [13].
N-(2-(Trimethylsilyl)-3-furyl)carbamic acid 1,1-dimethyl-
ethyl ester (4j, C12H21NO3Si)
N-(2-Phenyl-3-furyl)carbamic acid 1,1-dimethylethyl ester
(6a)
Yellow crystals (52%); m.p.: 104–106 °C; 1H NMR
(CDCl3): d = 0.20 (s, 9H, Si(CH3)3), 1.41 (s, 9H,
C(CH3)3), 6.07 (bs, 1H, NH), 6.61 (bs, 1H, H4), 7.37
Pathway A: Yellow oil (68%); Pathway B: Yellow oil
(68%); 1H NMR and 13C NMR spectra were identical with
those described in Ref. [13].
3
5
(dd, 1H, H5, J = 2.0 Hz, J = 0.4 Hz) ppm; 13C NMR
(CDCl3): d = 2.1 (q, Si(CH3)3), 29.8 (q, C(CH3)3), 81.9 (s,
C(CH3)3), 108.8 (d, C4), 126.6 (s, C3), 136.2 (s, C2), 147.5
(d, C5), 154.9 (s, NHCO) ppm.
N-(2-(4-Chlorophenyl)-3-furyl)carbamic acid 1,1-dimeth-
ylethyl ester (6b)
Pathway A: Pale yellow solid (53%); m.p.: 89–93 °C;
Pathway B: The reaction was carried out according to the
general procedure of pathway B, with the following
modification: before purification by column chromatogra-
phy after solvent evaporation the residue was triturated
with DIPE and the product 6b isolated from the filtrate.
Flash column chromatography (eluent PE–EtOAc; 10:1)
N-(2-Methyl-3-furyl)carbamic acid 1,1-dimethylethyl ester
(4k, C10H15NO3)
1
White solid (96%); m.p.: 65–68 °C; H NMR (CDCl3):
d = 1.44 (s, 9H, C(CH3)3), 2.15 (s, 3H, CH3), 5.86 (bs, 1H,
NH), 6.43 (bs, 1H, H4), 7.09 (d, 1H, H5, J = 2.0 Hz)
3
ppm; 13C NMR (CDCl3): d = 11.3 (q, CH3), 28.5 (q,
123

1356
K. Kolodziejczyk et al.
yielded 74%; m.p.: 89–93 °C; 1H NMR and 13C NMR
spectra were identical with those described in Ref. [13].
Procedure B: To a solution of LDA, prepared from
7.9 cm3 n-BuLi (19.0 mmol, 2.4 M in n-hexane) and
2.5 cm3 dry diisopropylamine (19.0 mmol) dissolved in
2.5 cm3 dry THF under nitrogen, was added dropwise a
solution of 1.0 g furan-3-carboxylic acid (2, 8.92 mmol) in
10 cm3 dry THF at -70 °C. The mixture was stirred for
1 h in a range -90 to -60 °C. To the reaction mixture was
added dropwise 7.9 g triisopropylborate (71.2 mmol) at
-90 to -80 °C. During overnight stirring, the reaction
mixture was warmed to room temperature and the resulting
mixture was then dissolved in 40 cm3 water. The solution
was washed with Et2O (2 9 30 cm3) and the aqueous layer
was acidified with 2 M HCl and left overnight for
crystallization in a fridge. The crystals were isolated by
filtration and washed with 10 cm3 of a cooled mixture of
H2O and EtOH (1:1) to provide 0.57 g (41%) 7b.
N-(2-(4-Fluorophenyl)-3-furyl)carbamic acid 1,1-dimeth-
ylethyl ester (6c)
Pathway A: Pale yellow crystals (72%); m.p.: 68–71 °C;
Pathway B: 75%; m.p.: 68–71 °C; 1H NMR and 13C NMR
spectra were identical with those described in Ref. [13].
2-Iodofuran-3-carboxylic acid (7a, C5H3IO3)
To a solution of LDA, prepared from 15.7 cm3 n-BuLi
(30.8 mmol, 1.96 M in hexane) and 4.32 cm3 dry diiso-
propylamine (30.8 mmol) in 10 cm3 dry THF under
nitrogen, was added dropwise 1.5 g furan-3-carboxylic
acid (2, 13.4 mmol) dissolved in 10 cm3 dry THF at -80 °C.
The mixture was then warmed from -80 to -30 °C within
3 h. The reaction mixture was then treated dropwise with a
solution of 3.73 g I2 (13.7 mmol) in 40 cm3 dry Et2O at -90
to -80 °C. After 1 h the reaction mixture was warmed to
room temperature and kept at that temperature for 4 h. The
resulting mixture was then dissolved in 70 cm3 water and the
solution washed with Et2O (3 9 50 cm3). The aqueous layer
was acidified with 2 M HCl to afford a brown oil which was
separated from the aqueous phase and then crystallized. The
crude product was triturated with a cooled mixture of H2O
and EtOH (1:1), isolated by filtration, and dried under
reduced pressure to give 1.82 g (57%) 7a as a bright brown
2-(Tributylstannyl)furan-3-carboxylic acid
(7c, C17H30O3Sn)
To a solution of LDA, prepared from 18.3 cm3 n-BuLi
(37.4 mmol, 2.04 M in hexane) and 4.9 cm3 dry diisopro-
pylamine (37.4 mmol) dissolved in 10 cm3 dry THF under
nitrogen, was added dropwise a solution of 2.0 g furan-3-
carboxylic acid (2, 17.8 mmol) in 15 cm3 dry THF at -90
to -60 °C. The mixture was then stirred for 1 h below
-60 °C. Afterwards, 8.0 g tributyltin chloride (17.8 mmol)
was added to the reaction mixture dropwise at -80 to
-60 °C. During overnight stirring the reaction mixture was
warmed to room temperature and then poured into 15 cm3
water. The solution was acidified with 2 M HCl and
extracted with Et2O (2 9 15 cm3). The organic phases
were combined and dried over Na2SO4, the solvent was
evaporated, and the yellow liquid obtained was purified by
flash column chromatography with PE–EtOAc (10:1) as the
eluent, affording 6.35 g (89%) 7c. 1H NMR (CDCl3):
d = 0.81 (t, 9H, CH2CH2CH2CH3, 3J = 7.0 Hz), 1.06–
1.16 (m, 6H, CH2CH2CH2CH3), 1.18–1.33 (m, 6H,
CH2CH2CH2CH3) 1.37–1.56 (m, 6H, CH2CH2CH2CH3),
6.69 (d, 1H, H4, 3J = 1.8 Hz), 7.59 (d, 1H, H5,
3J = 1.8 Hz), 12.10 (bs, 1H, COOH) ppm; 13C NMR
(CDCl3): d = 10.6 (t, CH2CH2CH2CH3), 13.5 (q,
CH2CH2CH2CH3), 27.0 (t, CH2CH2CH2CH3), 28.9 (t,
CH2CH2CH2CH3), 109.7 (d, C4), 128.7 (s, C3), 148.0 (s,
C5), 171.1 (s, COOH), 175.4 (s, C2) ppm.
1
solid. m.p.: 148–150 °C; H NMR (CDCl3): d = 7.61 (d,
1H, H4, 3J = 1.6 Hz), 7.80 (d, 1H, H5, 3J = 1.6 Hz), 10.53
(bs, 1H, COOH) ppm; 13C NMR (CDCl3): d = 98.8 (s, C2),
111.9 (d, C4), 122.7 (s, C3), 147.7 (d, C5), 166.7 (s, CO)
ppm.
2-Boronofuran-3-carboxylic acid (7b, C5H5BO5)
Procedure A: To a solution of LDA, prepared from
23.0 cm3 n-BuLi (44.5 mmol, 1.94 M in hexane) and
6.2 cm3 dry diisopropylamine (44.5 mmol) dissolved in
10 cm3 dry THF under nitrogen, was added dropwise a
solution of 2.0 g furan-3-carboxylic acid (2, 17.8 mmol) in
10 cm3 dry THF at -80 °C. The mixture was warmed to
-50 °C over a period of 2 h. To the reaction mixture was
added dropwise 7.9 g trimethylborate (71.2 mmol) at -90
to -80 °C. After 1 h the reaction mixture was warmed to
room temperature, the resulting mixture dissolved in
50 cm3 water, and the solution washed with Et2O
(2 9 30 cm3). The aqueous layer was acidified with 2 M
HCl and left overnight for crystallization in a fridge. The
white crystals were isolated by filtration and washed with a
cooled mixture of H2O and EtOH (1:1) to afford 1.87 g
(67%) 7b. m.p.: 154–156 °C; 1H NMR (DMSO-d6):
d = 6.76 (d, 1H, H4, 3J = 1.8 Hz), 7.66 (d, 1H, H5,
3J = 1.8 Hz), 8.95 (bs, 2H, B(OH)2) ppm; 13C NMR
(DMSO-d6): d = 111.3 (d, C4), 128.6 (s, C3), 146.8
(d, C5), 159.1 (s, C2), 168.2 (s, COOH) ppm.
General procedure for compounds 8a–8c
2-Iodofuran-3-carboxylic acid (7a, 1.09 mmol), K2CO3
(2.18 mmol), and phenylboronic acid 5a–5c (1.20 mmol)
were dissolved in 5 cm3 H2O under argon. Then 1–2 mol%
Pd(OAc)2 (0.0178 mmol) was added. The reaction mixture
was stirred for 4 h at room temperature. Then the palla-
dium powder was isolated by filtration through Celite. The
123

Synthesis of potential fungicides
1357
H30, H50, 3J = 7.0 Hz), 7.48 (d, 2H, H20, H60,
3J = 7.0 Hz) ppm; 13C NMR (CDCl3): d = 105.5
(d, C4), 120.7 (d, C30, C50), 122.8 (s, C3), 122.9 (d, C40),
126.0 (s, C10), 126.2 (d, C20,60), 126.9 (s, C2), 138.1
(d, C5) ppm.
filtrate was diluted with 10 cm3 water and acidified with
4 cm3 2 M HCl and a crude product precipitated. The
precipitate was isolated by filtration, washed with cold
water, and dried under reduced pressure to give the prod-
ucts 8a–8c (50–91%).
2-(4-Chlorophenyl)-3-furanamine (9b, C10H8ClNO)
1
2-Phenylfuran-3-carboxylic acid (8a, C11H8O3)
1
Dark purple material (90%); H NMR (CDCl3): d = 3.16
Cream solid (91%); m.p.: 150–153 °C; H NMR (CDCl3):
(bs, 2H, NH2), 6.02 (d, 1H, H4, 3J = 2.0 Hz), 7.08 (d, 1H,
d = 6.90 (d, 1H, H4, 3J = 2.0 Hz), 7.42 (d, 1H, H5,
3J = 2.0 Hz), 7.44–7.48 (m, 3H, H40, H30, H50), 7.94–7.99
(m, 2H, H20, H60) ppm; 13C NMR (CDCl3): d = 112.9 (s,
C3), 113.3 (d, C4), 128.2 (d, C20, C60), 128.7 (d, C30, C50),
129.5 (s, C10), 129.7 (d, C40), 141.5 (d, C5), 158.9 (s, C2),
169.1 (s, CO) ppm.
3
3
H5, J = 2.0 Hz), 7.19 (d, 2H, H30, H50, J = 9.0 Hz),
7.34 (d, 2H, H20, H60, 3J = 9.0 Hz) ppm; 13C NMR
(CDCl3): d = 108.2 (d, C4), 124.3 (d, C30, C50), 128.9 (d,
C20, C60), 129.4 (s, C10), 130.3 (s, C3), 130.8 (s, C2), 135.4
(s, C40), 140.9 (d, C5) ppm.
2-(4-Fluorophenyl)-3-furanamine (9c, C10H8FNO)
1
2-(4-Chlorophenyl)furan-3-carboxylic acid
(8b, C11H7ClO3)
Dark purple material (81%); H NMR (CDCl3): d = 2.53
(bs, 2H, NH2), 6.18 (d, 1H, H4, 3J = 2.0 Hz), 7.09 (dd, 2H,
H20, H60, 3J = 9.0 Hz), 7.23 (d, 1H, H5, 3J = 2.0 Hz),
7.54 (dd, 2H, H30, H50, 3J = 9.0 Hz, 3JH–F = 3.8 Hz) ppm;
13C NMR (CDCl3): d = 108.2 (d, C4), 115.7 (d, C30, C50,
1
Gray solid (50%); m.p.: 181–184 °C; H NMR (CDCl3):
3
d = 6.85 (d, 1H, H4, J = 2.0 Hz), 7.53 (d, 2H, H30, H50,
3
3J = 9.0 Hz), 7.82 (d, 1H, H5, J = 2.0 Hz), 7.96 (d, 1H,
3
H20, H60, J = 9.0 Hz), 12.96 (bs, 1H, COOH) ppm; 13C
3
2JC–F = 21.6 Hz), 124.9 (d, C20, C60, JC–F = 7.8 Hz),
NMR (CDCl3): d = 113.4 (d, C4), 115.0 (s, C3), 128.2 (s,
C10), 128.3 (d, C20, C60), 129.6 (d, C30, C50), 133.9 (s, C40),
142.7 (d, C5), 154.6 (s, C2), 164.1 (s, CO) ppm.
128.1 (s, C10, 4JC–F = 3.4 Hz), 128.2 (s, C3), 135.8 (s, C2),
140.5 (d, C5), 160.8 (d, C40, JC–F = 245.3 Hz) ppm.
2-(4-Fluorophenyl)furan-3-carboxylic acid
(8c, C11H7FO3)
General procedure for preparation of acyl chlorides
11a–11b
1
Cream solid (50%); m.p. 135–138 °C; H NMR (CDCl3):
d = 6.84 (d, 1H, H4, 3J = 2.0 Hz), 7.30 (dd, 2H, H20, H60,
3J = 9.0 Hz), 7.80 (d, 1H, H5, 3J = 2.0 Hz), 7.99 (dd, 2H,
To
a suspension of 1-methyl-4-(trifluoromethyl)-1H-
pyrrole-3-carboxylic acid 10a [32] or 1-methyl-3-(trifluo-
romethyl)-1H-pyrazole-4-carboxylic acid 10b [32] (3.4
mmol) in 10 cm3 dry Et2O, PCl5 (3.7 mmol) was added.
The suspension was stirred for 2–4 h at room temperature
until the formation of a transparent solution. The solvent
was then evaporated under vacuum at 35–40 °C. The
resulting acid chlorides 11a–11b were obtained in quanti-
tative yield.
3
H30, H50, 3J = 9.0 Hz, JH–F = 2.9 Hz), 12.86 (bs, 1H,
COOH) ppm; 13C NMR (CDCl3): d = 113.2 (d, C4), 114.3
(s, C3), 115.2 (d, C30, C50, 2JC–F = 21.8 Hz), 125.9 (d, C10,
3
4JC–F = 3.3 Hz), 130.3 (d, C20, C60, JC–F = 8.6 Hz),
142.4 (d, C5), 155.0 (s, C2), 162.4 (d, C40,
JC–F = 247.3 Hz), 164.2 (s, CO) ppm.
General procedure for compounds 9a–9c
1-Methyl-4-(trifluoromethyl)-1H-pyrrole-3-carbonyl
chloride (11a, C7H5ClF3NO)
The N-tert-butylcarbamates 6a–6c (0.20 mmol) were dis-
solved in 2.5 cm3 dry CH2Cl2 and then treated with dry
trifluoroacetic acid (TFA, 4.0 mmol, dried over molecular
sieves) under nitrogen at room temperature for 4–20 h. The
reaction mixture was then neutralized with. satd. NaHCO3
solution, extracted with Et2O (5 9 10 cm3), and the com-
bined extracts were dried over Na2SO4. The solvent was
removed under vacuum at 30–40 °C, providing the amines
9a–9c as brown oils in 52–95% yield. The amines are
relatively unstable and undergo decomposition in 1–2 days
of storage.
1
Brown solid (100%); m.p.: 64–66 °C; H NMR (CDCl3):
4
d = 3.75 (s, 3H, CH3), 7.04 (dd, 1H, H5, J = 2.7 Hz,
4
4JH–F = 1.6 Hz), 7.54 (d, 1H, H2, J = 2.7 Hz) ppm; 13C
NMR (CDCl3): d = 37.3 (q, CH3), 115.5 (q, C4,
2JC–F = 38.5 Hz), 116.8 (s, C3), 121.9 (q, CF3,
3
JC–F = 266.9 Hz), 126.0 (q, C5, JC–F = 6.0 Hz), 135.2
(d, C2), 157.6 (s, COCl) ppm.
1-Methyl-3-(trifluoromethyl)-1H-pyrazole-4-carbonyl
chloride (11b, C6H4ClF3N2O)
1
Yellow oil (100%); H NMR (CDCl3): d = 4.03 (s, 3H,
CH3), 8.18 (s, 1H, H2) ppm; 13C NMR (CDCl3): d = 38.9
(q, CH3), 155.5 (s, C4), 118.4 (q, CF3, JC–F = 269.9 Hz),
2-Phenyl-3-furanamine (9a, C10H9NO)
1
Brown oil (61%); H NMR (CDCl3): d = 3.05 (bs, 2H,
2
138.9 (d, C5), 140.5 (q, C3, JC–F = 39.6 Hz), 155.4
(s, COCl) ppm.
3
NH2), 6.10 (d, 1H, H4, J = 2.0 Hz), 7.09 (t, 1H, H40,
3
3J = 7.0 Hz), 7.16 (d, 1H, H5, J = 2.0 Hz), 7.32 (t, 2H,
123

1358
K. Kolodziejczyk et al.
General procedure for formation of compounds 1a–1f
N-(2-(4-Fluorophenyl)-3-furyl)-1-methyl-4-(trifluoro-
methyl)-1H-pyrrole-3-carboxamide (1c, C17H12F4N2O2)
According to procedure D 1c was obtained as a yellow
Procedure C: To a solution of amine (9a–9c, 2.07 mmol) in
7 cm3 dry CH2Cl2 DMAP (3.11 mmol) was added and
then, dropwise, the acid chloride 11a–11b (2.07 mmol)
dissolved in 7 cm3 dry CH2Cl2. The resulting solution was
stirred at room temperature for 23–40 h. Then the reaction
mixture was quenched with 5 cm3 2 M HCl, extracted with
CH2Cl2 (2 9 15 cm3), the combined organic layers dried
over Na2SO4, and then the solvent was evaporated,
affording the desired amide.
1
solid (53%); m.p.: 50–54 °C; H NMR (CDCl3): d = 3.62
(s, 3H, CH3), 6.91 (dd, 1H, H5, 4J = 2.7 Hz,
4JH–F = 1.6 Hz), 6.94 (d, 1H, H40, 3J = 2.0 Hz), 7.02
(dd, 2H, H200, H600, 3J = 8.8 Hz), 7.28 (d, 1H, H2,
4J = 2.7 Hz), 7.31 (d, 1H, H50, 3J = 2.0 Hz), 7.49 (s,
1H, NH), 7.51 (dd, 2H, H300, H500, 3J = 8.8 Hz,
3JH–F = 3.5 Hz) ppm; 13C NMR (CDCl3): d = 36.8 (q,
2
CH3), 110.2 (d, C40), 111.6 (q, C4, JC–F = 36.2 Hz),
Procedure D: To
a
solution of amine (9a–9c,
115.8 (d, C300, C500, 2JC–F = 21.8 Hz), 117.0 (s, C3), 119.8
(s, C30), 123.3 (q, CF3, JC–F = 266.2 Hz), 124.1 (q, C5,
3JC–F = 6 Hz), 126.4 (s, C20), 127.0 (d, C200, C600,
3JC–F = 8 Hz), 129.2 (d, C2), 140.8 (d, C50), 141.9 (s,
C100), 161.0 (s, NHCO), 162.0 (d, C400, JC–F = 247.6 Hz)
ppm.
2.58 mmol) in 7 cm3 dry CH2Cl2 triethylamine
(6.45 mmol) was added. The acid chloride 11a–11b
(2.58 mmol) dissolved in 5 cm3 dry CH2Cl2 was then
added dropwise. The resulting solution was stirred at
room temperature for 38 h. Then the reaction mixture
was quenched with 10 cm3 2 M HCl, extracted with
CH2Cl2 (3 9 40 cm3), dried over Na2SO4 and purified
by flash column chromatography affording the amides
1a–1f.
1-Methyl-N-(2-phenyl-3-furyl)-3-(trifluoromethyl)-1H-pyr-
azole-4-carboxamide (1d, C16H12F3N3O2)
According to procedure D 1d was obtained as a pale brown
1
solid foam (26%); m.p.: 145–150 °C; H NMR (CDCl3):
d = 3.86 (s, 3H, CH3), 6.92 (bs, 1H, H40), 7.22 (m, 1H,
1-Methyl-N-(2-phenyl-3-furyl)-4-(trifluoromethyl)-1H-
pyrrole-3-carboxamide (1a, C17H13F3N2O2)
According to procedure C 1a was obtained as a yellow
H400), 7.29–7.37 (m, 2H, H300, H500), 7.32 (d, 1H, H50,
3
3J = 2.0 Hz), 7.49 (d, 2H, H200, H600, J = 7.0 Hz), 7.69
(bs, 1H, NH), 7.93 (s, 1H, H5) ppm; 13C NMR (CDCl3):
d = 38.8 (q, CH3), 108.9 (d, C40), 115.7 (s, C4), 118.6 (s,
C30), 120.0 (q, CF3, JC–F = 269.2 Hz), 124.1 (d, C200,
C600), 126.8 (d, C400), 127.9 (d, C300, C500), 128.8 (s, C20),
135.1 (d, C5), 136.0 (s, C100), 140.0 (d, C50), 141.4 (q, C3,
2JC–F = 34.5 Hz), 157.8 (s, NHCO) ppm.
1
solid (38%); m.p.: 51–53 °C; H NMR (CDCl3): d = 3.61
(s, 3H, CH3), 6.90 (dd, 1H, H5, 4J = 2.7 Hz,
4JH–F = 1.6 Hz), 7.00 (d, 1H, H40, 3J = 2.0 Hz), 7.19
4
(m, 1H, H400), 7.25 (d, 1H, H2, J = 2.7 Hz), 7.29–7.38
(m, 2H, H300, H500), 7.33 (d, 1H, H50), 7.53 (d, 2H, H200,
H600, 3J = 7.0 Hz), 7.59 (bs, 1H, NH) ppm; 13C NMR
(CDCl3): d = 35.8 (q, CH3), 109.0 (d, C40), 110.7 (q, C4,
2JC–F = 36.2 Hz), 116.2 (s, C3), 119.3 (s, C30), 121.2 (q,
N-(2-(4-Chlorophenyl)-3-furyl)-1-methyl-3-(trifluoro-
methyl)-1H-pyrazole-4-carboxamide
(1e, C16H11ClF3N3O2)
3
CF3, JC–F = 266.3 Hz), 123.0 (q, C5, JC–F = 6.1 Hz),
124.1 (d, C200, C600), 126.4 (d, C400), 127.8 (d, C300, C500),
128.0 (d, C2), 129.2 (s, C20), 139.9 (d, C50), 141.2 (s, C100),
159.9 (s, NHCO) ppm.
According to procedure D, 1e was obtained as a yellow
solid (35%); m.p.: 172–175 °C; 1H NMR (CDCl3):
d = 3.98 (s, 3H, CH3), 6.99 (br d, 1H, H40), 7.38 (d, 2H,
3
3
H300, H500, J = 8.8 Hz), 7.41 (d, 1H, H50, J = 2.0 Hz),
N-(2-(4-Chlorophenyl)-3-furyl)-1-methyl-4-(trifluoro-
methyl)-1H-pyrrole-3-carboxamide
(1b, C17H12ClF3N2O2)
3
7.53 (d, 2H, H200, H600, J = 8.8 Hz), 7.61 (bs, 1H, NH),
8.03 (s, 1H, H5) ppm; 13C NMR (DMSO-d6): d = 39.4 (q,
CH3), 112.3 (d, C40), 115.7 (s, C4), 120.4 (s, C30), 120.8 (q,
CF3, JC–F = 268.8 Hz), 126.0 (d, C200, C600), 128.7 (d, C300,
C500), 128.7 (s, C20), 131.7 (s, C400), 134.4 (d, C5), 139.4 (s,
C3, 2JC–F = 37.3 Hz), 141.9 (d, C50), 142.7 (s, C100), 159.0
(s, NHCO) ppm.
According to procedure D 1b was obtained as an orange
1
solid (53%); m.p.: 66–71 °C; H NMR (CDCl3): d = 3.62
(s, 3H, CH3), 6.92 (s, 1H, H5), 6.93 (d, 1H, H40,
3J = 2.0 Hz), 7.26–7.32 (m, 4H, H300, H500, J = 8.8 Hz,
3
3
H50, H2), 7.46 (d, 2H, H200, H600, J = 8.8 Hz), 7.52 (bs,
1H, NH) ppm; 13C NMR (CDCl3): d = 36.9 (q, CH3),
N-(2-(4-Fluorophenyl)-3-furyl)-1-methyl-3-(trifluoro-
methyl)-1H-pyrazole-4-carboxamide
(1f, C16H11F4N3O2)
2
110.4 (d, C40), 111.6 (q, C4, JC–F = 36.2 Hz), 117.0 (s,
C3), 120.5 (s, C30), 123.3 (q, CF3, JC–F = 266.2 Hz), 124.1
3
(q, C5, JC–F = 6.2 Hz), 126.2 (d, C200, C600), 128.6
According to procedure D 1f was obtained as a yellow
solid (67%); m.p. 136–139 °C; 1H NMR (CDCl3):
d = 3.88 (s, 3H, CH3), 6.86 (br d, 1H, H40), 7.02 (dd,
2H, H200, H600, 3J = 8.8 Hz), 7.30 (d, 1H, H50,
(s, C400), 129.0 (d, C300, C500), 129.2 (d, C2), 133.1
(s, C20), 141.1 (d, C50), 141.6 (s, C100), 160.9 (s, NHCO)
ppm.
123

Synthesis of potential fungicides
1359
3J = 2.0 Hz), 7.47 (dd, 2H, H300, H500, 3J = 8.8 Hz,
3JH–F = 3.5 Hz), 7.59 (bs, 1H, NH), 7.93 (bs, 1H, H5)
ppm; 13C NMR (CDCl3): d = 37.7 (q, CH3), 108.0 (d,
12. Walter H, Trah S, Schneider H (2001) WO 2001049664, CAN
135:92539
13. Stanetty P, Kolodziejczyk K, Roiban GD, Mihovilovic MD
(2006) Synlett 5:789
14. Campbell MM, Kaye AD, Sainsbury M (1982) Tetrahedron
38:2783
15. Shioiri T, Ninomiya K, Yamada S (1972) J Am Chem Soc
94:6203
16. Snieckus V (1990) Chem Rev 90:879
17. Muchowski JM, Venuti MC (1980) J Org Chem 45:4798
18. Carpenter AJ, Chadwick DJ (1985) Tetrahedron 41:3803
19. Watanabe M, Snieckus V (1980) J Am Chem Soc 102:1457
20. Sammes PG, Dodsworth DJ (1979) Chem Commun 33
21. De Silva SO, Watanabe M, Snieckus V (1979) J Org Chem
44:4802
2
C40), 113.8 (d, C300, C500, JC–F = 21.8 Hz), 114.5 (s, C4),
117.0 (s, C30), 118.8 (q, CF3, JC–F = 269.1 Hz), 124.0 (s,
3
C20), 124.9 (d, C200, C600, JH–F = 8 Hz), 133.8 (d, C5),
2
136.3 (q, C3, JC–F = 37.2 Hz), 138.8 (d, C50), 140.3 (s,
C100), 157.5 (s, NHCO), 159.6 (d, C400, JC–F = 286.3 Hz)
ppm.
Acknowledgments We thank Syngenta Crop Protection, Basel, for
financial support of this project and for providing acids 10a and 10b.
22. Slocum DW, Gierer PL (1976) J Org Chem 41:3668
23. Zhang P, Terefenko EA, Slavin J (2001) Tetrahedron Lett
42:2097
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