Synthesis of new halo-containing acetylenes and their application to the synthesis of azoles

Article abstract of DOI:10.1016/j.tetlet.2004.04.106

The convenient synthesis of ten halo- and an isoxazole-containing acetylenes from the reaction of acetylenes with n-butyl lithium and subsequent reaction with an electrophile agent (ethyl trichloroacetate, ethyl dichloroacetate, trifluoroacetic anhydride,

Full text of DOI:10.1016/j.tetlet.2004.04.106

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4935–4938
Synthesis of new halo-containing acetylenes and their
application to the synthesis of azoles
*
Marcos A. P. Martins, Daniel J. Emmerich, Claudio M. P. Pereira, Wilson Cunico,
Marcelo Rossato, Nilo Zanatta and Helio G. Bonacorso
N ꢀu cleo de Qu ꢀı mica de Heterociclos (NUQHIMHE), Universidade Federal de Santa Maria,
9
7.105-900-Santa Maria, RS 97.105- 900 Santa Maria, RS, Brazil
Received 6 September 2003; revised 17 April 2004; accepted 20 April 2004
Available online 18 May 2004
Abstract—The convenient synthesis of ten halo- and an isoxazole-containing acetylenes from the reaction of acetylenes with n-butyl
lithium and subsequent reaction with an electrophile agent (ethyl trichloroacetate, ethyl dichloroacetate, trifluoroacetic anhydride,
3
-methylisoxazol-5-carbonyl chloride, carbon tetrachloride and 1,1,1-trifluoro-4-ethoxy-3-buten-2-one) in moderated to good yields
is reported. The application of 1,1,1-trichloro-4-phenyl-3-butyn-2-one on the synthesis of two azoles is also showed.
2004 Elsevier Ltd. All rights reserved.
ꢀ
Recently, a variety of important biological activities of
acetylenic compounds have been published. For exam-
ple, Efavirenz exhibits nonnucleoside HIV-1 reverse
transcriptase inhibition and acetylenic heterocycles are
and demonstrated their usefulness in heterocyclic prep-
14b;17
13;15;16
arations, for example, isoxazoles, pyrazoles,
pyrazolium chlorides, pyrrolidinones, pyrimidines,
18
19
20
21
22
23
pyridines, thiazines and diazepines.
used as muscarinic M agonists for the treatment of
1
1
;2
Alzheimer’s disease. Acetylenic derivatives are also
useful precursor in synthetic organic chemistry, in
special, for the preparation of 1,2,3-triazoles from the
1
azides.
In continuation of our research program to develop new
halo-heterocyclic precursors, we are reporting the
methodology to synthesize a series of halo- and isoxa-
zole-containing acetylenes. Thus, the aim of this work is
to report the synthesis of acetylenes 2–8 from the reac-
tion of acetylene 1 with n-butyl lithium and subsequent
reaction with an electrophile, often in the presence of
boron trifluoride etherate (Scheme 1).
3;4
,3-dipolar cycloaddition with organic and inorganic
5
One of the most efficient methods for the preparation of
acylacetylenes is the direct acylation of metal-acetyl-
enides. The literature reports the reaction of activated
acylating reagents such as acid chlorides or anhydrides
24
Ziegler et al. demonstrated the preparation of a series
of halo alkynes, where the compound 7a was prepared
by shaking the alkyne with a large excess of sodium
6
with various types of metal-acetylenides such as lithium-,
7
8
9
10
11
magnesium-, copper-, cadmium-, silicium-, silver-
and tin-acetylenides that have been used to obtain the
corresponding acylacetylenes.
12
3
hydroxide and chlorine. Zweifel et al. proposed the
preparation of the same compound from the reaction of
the alkyne in n-butyl lithium in the presence of n-chlo-
rosuccinimide. In a recent paper, Andrew and Mellor
25
In recent years, we have developed a general synthesis of
a large number of 1,1,1-trihalo-4-methoxy-alken-2-
reported the synthesis of a novel series of acetylenes,
including the 6-phenyl-1,1,1-trifluoro-3-hexen-5-yne-2-
one (8a) in low yield (37%), using Grignard and organo-
lithium reagents. So far, phenyl acetylenes 2–6 have not
been reported. In this work, phenyl acetylenes were
obtained in moderate to good yields.
13;14
ones,
important halogen-containing building blocks,
Keywords: Acetylenes; Heterocycles; Pyrazoles; Isoxazoles.
*
Corresponding author. Tel.: +55-55-220-8756; fax: +55-55-220-8031;
e-mail: mmartins@base.ufsm.br
URL: http://www.ufsm.br/nuquimhe
The synthesis of compounds 2–4, 8 were carried
out from the reaction of lithium acetylenide with the
0
040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.106

4936
M. A. P. Martins et al. / Tetrahedron Letters 45 (2004) 4935–4938
O
i
R
Cl CCl3
CCl3
Cl
R
Cl
CCl3
8
5 %
R
CCl3
2
a,b
7
O
R
CCl3
Cl
ii
R
Ph
85 %
6
CHCl2
HO OH
3
a
Scheme 2.
iii
5 %
R
7
4
a,b,c CF3
used by these authors for the synthesis of isoxazoles,
from the reaction of trifluoromethyl acetylenes with
hydroxylamine, furnished a mixture of oxime and isoxa-
zoline. Also, the reaction of acetylenes with hydrazine in
acetonitrile at room temperature, lead to a mixture of
O
iv
7 %
R
H
Ph
6
5a
1a-c
O
29
pyrazole and pyrazoline.
Me
N
v
5 %
R
CCl3
6
6
In this work, 2a was used to show the synthetic potential
of this compound towards reactions with hydroxylamine
and phenyl hydrazine (Scheme 3). From a similar pro-
cedure reported by Linderman et al., in this work only
4,5-dihydroisozazole (9) and the pyrazole (10), respec-
tively, were obtained, instead of the mixture of products.
6
a,c
vi
29
Ph
Cl
2 %
7a
O
The physical and spectral data of compounds 9, 10
15c;17b;30
obtained are in accordance with the literature.
vii
Ph
CF3
8
0 %
8
a
Unless otherwise indicated, all common reagents and
solvents were used as obtained from commercial sup-
plies without further purifications. 1,1,1-Trifluoro-4-
Scheme 1. Reagents and conditions: (i) (1) n-BuLi, THF, 30 min,
78 ꢁC; (2) Cl CC(O)OEt, 2 equiv BF ÆOEt, rt, 2 h. (ii) (1) n-BuLi,
CHC(O)OEt, 2 equiv BF ÆOEt, rt, 2 h. (iii)
1) n-BuLi, THF, 30 min, )78 ꢁC; (2) (F CCO) O, 3 equiv BF ÆOEt, rt,
.5 h (iv) (1) n-BuLi, THF, 30 min, )78 ꢁC; (2) isoxazol-5-carbonyl
)
3
3
THF, 30 min, )78 ꢁC; (2) Cl
(
2
3
3
2
3
ethoxy-3-buten-2-one was synthesized using the meth-
13a
1
odology developed in our laboratory.
points were taken on a melting point microscope Reic-
The melting
chloride, rt, 45 min. (v) (1) n-BuLi, THF, 30 min, )78 ꢁC; (2) CCl
excess), )78 ꢁC to rt, 45 min. (vi) (1) n-BuLi (excess), THF, 30 min,
78 ꢁC; (2) CCl , rt, 1 h. (vii) (1) n-BuLi, THF, 30 min, )78 ꢁC; (2)
CF C(O)CH@CHOEt, 2 equiv BF ÆOEt, rt, 2 h.
4
(
1
13
hert Thermovar and are uncorrected. H and C NMR
spectra were recorded on a Bruker DPX 400 (1H at
)
4
3
3
4
00.13 MHz and 13C at 100.62 MHz) in 5 mm sample
tubes at 298 K (digital resolution ±0.01 ppm) in CDCl
TMS solutions.
3
/
corresponding electrophile agent, in the presence of
2
2
equiv of boron trifluoride diethyl etherate. The use of
equiv of boron trifluoride diethyl etherate was required
to improve the product yields. In the synthesis of com-
pounds 5–7 the use of Lewis acid was not necessary.
1
. Synthesis of 1,1,1-trichloro-4-phenyl-3-butyn-2-one 2a
The preparation of compounds 6 and 7 from the same
reagents with modification in the reaction conditions was
unexpected. To obtain 7a a solution of carbon tetra-
chloride in THF was added to an excess of lithium
acetylenide (molar ratio of 3:5) at )78 ꢁC, whereas, in the
synthesis of 6a–c, a solution of lithium acetylenide in
THF was added to an excess of carbon tetrachloride
1
.1. Typical procedure
To a stirred solution of phenyl acetylene (0.204 g,
mmol) in dry THF (10 mL) was added dropwise 1.6 M
2
solution of n-butyl lithium in hexane (1.5 mL) at )78 ꢁC
and under nitrogen. After stirring for 30 min, was added
to the mixture a solution of ethyl trichloroacetate
(
accordance with analogous results obtained by Zweifel
molar ratio of 1:3) at )78 ꢁC. The preparation of 7 is in
3
24
Ph
et al. and Ziegler et al. that reacted acetylenides with
electrophilic chlorine compounds to obtain chloroalky-
nes. On the other hand, the reaction mechanism for
preparation of 6 remains unclear. A possible explanation
is that the product 6 was obtained from compound 7 due
to the attack of the trichloromethyl anion on 7 and
subsequent elimination of a chlorine anion (Scheme 2).
HO
i
N
7
0 %
O
9
Cl3C
O
Ph
Ph
CCl3
2a
ii
N
Cl3C
N
7
5 %
Considering the importance of isoxazoles and pyrazoles
as biological active compounds,
Ph
1
26–28
Linderman and
0
29
Lonicar prepared trifluoromethyl functionalized acetyl-
enes with the objective to obtain a series of perfluoro-
alkyl substituted azoles. However, the synthetic route
Scheme 3. Reagents and conditions: (i) NH OHÆHCl, pyridine,
methanol, reflux, 12 h. (ii) NH NHPh, benzene, rt, 4 h.
2
2

M. A. P. Martins et al. / Tetrahedron Letters 45 (2004) 4935–4938
4937
(
(
0.28 mL, 2 mmol) and trifluoride diethyl etherate
0.5 mL) in dry THF (5 mL). The reaction was allowed
2. Rodriguez-Franco, M. I.; Dorronso, I.; Castro, A.;
Mart ꢀı nez, A.; Bad ꢀı a, A.; B ~a nos, J. E. Bioorg. Med. Chem.
2
003, 11, 2263.
. Zweifel, G.; Lewis, W.; On, H. P. J. Am. Chem. Soc. 1979,
01, 5101.
. (a) Legros, J.; Crousse, B.; Delpon, D.-B.; B ꢀe gu ꢀe , J.-P.
J. Fluorine Chem. 2001, 107, 121; (b) Tykwinski, R. R.;
Zhao Synlett 2002, 12, 1939; Brown, H. C.; Racherla,
U. S.; Sing, S. M. Tetrahedron Lett. 1984, 25, 2411.
to warm to room temperature and the resulting mixture
was stirred at room temperature for 2 h. After this time,
3
4
1
a saturated solution of NH
the organic layer was extracted with dichloromethane
3 · 15 mL). The organic phase was dried (Na SO ) and
4
Cl (10 mL) was added and
(
2
4
the solvent was evaporated. The residue was purified by
column chromatography on silica gel 230–400 mesh,
hexane/ethyl acetate (10:1). Selected physical and spec-
tral data of compounds 2–8 are presented in Ref. 31.
5. Degl’lnnocenti, A.; Scafato, P.; Capperucci Bartoletti, L.
A.; Mordini, A.; Reginato, G. Tetrahedron Lett. 1995, 36,
9031.
6
7
8
9
. Kroeger, J. W.; Niewland, J. A. J. Am. Chem. Soc. 1936,
8, 1861.
. Normant, J. F.; Bourgain, M. Tetrahedron Lett. 1970, 11,
659.
. Yashina, G.; Zarva, T. V.; Kaigordova, T. D.; Veresh-
chagin, L. I. Zh. Org. Khim. 1968, 4, 2104.
. Utimoto, K.; Tanaka, M.; Kitai, M.; Nozaki, H. Tetra-
hedron Lett. 1978, 18, 405.
5
2
2
. Synthesis of 1,1,1-trichloro-3-phenyl-2-propyne 6a
To a stirred solution of phenyl acetylene (0.510 g,
mmol) in dry THF (10 mL) was added dropwise 1.6 M
5
solution of n-butyl lithium in hexane (5 mmol, 3.12 mL)
at )78 ꢁC and under nitrogen. After stirring for 30 min,
the phenyl acetylenide obtained was added to the carbon
tetrachloride (15 mmol, 1.43 mL) at )78 ꢁC. The reac-
tion was allowed to warm to room temperature and the
resulting mixture was stirred at room temperature for
1
0. Davis, R. B.; Scheiber, D. H. J. Am. Chem. Soc. 1956, 78,
675.
1
11. Himbert, G. Angew. Chem. 1979, 91, 432; Angew. Chem.,
Int. Ed. Engl. 1979, 18, 405.
12. Kroeger, J. W.; Nieuwland, J. A. J. J. Am. Chem. Soc.
1
936, 58, 1861.
1
3. (a) Colla, A.; Martins, M. A. P.; Clar, G.; Krimmer, S.;
Fischer, P. Synthesis 1991, 6, 483; (b) Martins, M. A. P.;
Zoch, A. N.; Flores, A. F. C.; Clar, G.; Zanatta, N.;
Bonacorso, H. G. J. Heterocycl. Chem. 1995, 32, 739.
4. (a) Martins, M. A. P.; Bastos, G. P.; Bonacorso, H. G.;
Zanatta, N.; Flores, A. F. C.; Siqueira, G. M. Tetrahedron
Lett. 1999, 40, 4309; (b) Bonacorso, H. G.; Martins, M. A.
P.; Bittencourt, S. R. T.; Lourega, R. V.; Zanatta, N.;
Flores, A. F. C. J. Fluorine Chem. 1999, 99, 177.
4
5 min. The isolation of the product was similar to that
used in the synthesis of 2a. Selected physical and spec-
tral data of compound 6a are presented in Ref. 31.
1
3
. Synthesis of 1-chloro-2-phenylethyne 7a
To a stirred solution of phenyl acetylene (0.510 g,
mmol) in dry THF (10 mL) was added dropwise 1.6 M
1
5. (a) Martins, M. A. P.; Flores, A. C.; Freitag, R.; Zanatta,
N. J. Heterocycl. Chem. 1995, 32, 731; (b) Martins, M. A.
P.; Flores, A. C.; Freitag, R. A.; Zanatta, N. J. Heterocycl.
Chem. 1996, 33, 1223; (c) Martins, M. A. P.; Siqueira, G.
M.; Bastos, G. P.; Bonacorso, H. G.; Zanatta, N. J.
Heterocycl. Chem. 1996, 33, 1619; (d) Martins, M. A. P.;
Flores, A. F. C.; Bastos, G. P.; Zanatta, N.; Bonacorso, H.
G. J. Heterocycl. Chem. 1999, 36, 837; (e) Martins, M. A.
P.; Neto, M.; Sinhorin, A. P.; Bastos, G. P.; Zimmermann,
N. E. K.; Rosa, A.; Bonacorso, H. G.; Zanatta, N. Synth.
Commun. 2002, 32, 425.
5
solution of n-butyl lithium in hexane (5 mmol, 3.12 mL)
at )78 ꢁC and under nitrogen. After stirring for 30 min,
a solution of carbon tetrachloride (3 mmol, 0.28 mL) in
dry THF (5 mL) at )78 ꢁC, was added. The reaction was
allowed to warm to room temperature and the resulting
mixture was stirred at room temperature for 1 h. The
isolation of the product was similar to that used in the
synthesis of 2a. Selected physical and spectral data of
compound 7a are presented in Ref. 31.
1
1
6. Martins, M. A. P.; Sinhorin, A. P.; Zimmermann, N. E.
K.; Zanatta, N.; Bonacorso, H. G.; Bastos, G. P. Synthesis
2
001, 13, 1959.
7. (a) Braibante, M. E. F.; Martins, M. A. P.; Clar, G. J.
Heterocycl. Chem. 1993, 30, 1159; (b) Flores, A. C. F.;
Martins, M. A. P.; Rosa, A.; Flores, D. C.; Zanatta, N.;
Bonacorso, H. G. Synth. Commun. 2002, 32, 1585.
Acknowledgements
The authors thank the Conselho Nacional de Desen-
volvimento Cient ꢀı fico e Tecnol oꢀ gico (CNPq/PADCT),
Fundaßc ~a o de Amparo ꢁa pesquisa do Estado do Rio
Grande do Sul (FAPERGS) for financial support. The
fellowships from CNPq, CAPES and FAPERGS are
also acknowledged.
1
8. (a) Martins, M. A. P.; Pereira, C. M. P.; Sinhorin, A. P.;
Bastos, G. P.; Zimmermann, N. E. K.; Rosa, A.; Bona-
corso, H.; Zanatta, N. Synth. Commun. 2002, 32, 419; (b)
Martins, M. A. P.; Blanco, R. F.; Pereira, C. M. P.; Beck,
P.; Brondani, S.; Cunico, W.; Zimmermann, N. E. K.;
Bonacorso, H. G.; Zanatta, N. J. Fluorine Chem. 2002,
118, 69.
9. Zanatta, N.; Rosa, L. S.; Loro, E.; Bonacorso, H. G.;
Martins, M. A. P. J. Fluorine Chem. 2001, 107, 149.
1
References and notes
20. (a) Madruga, C. C.; Clerici, E.; Martins, M. A. P.;
Zanatta, N. J. Heterocycl. Chem. 1995, 32, 735; (b)
Zanatta, N.; Cortelini, M. F. M.; Carpes, M. J. S.;
Bonacorso, H. G.; Martins, M. A. P. J. Heterocycl. Chem.
1997, 34, 509; (c) Zanatta, N.; Madruga, C. C.; Marisco,
P. C.; Flores, D. C.; Bonacorso, H. G.; Martins, M. A. P.
J. Heterocycl. Chem. 2000, 37, 1213; (d) Zanatta, N.;
1
. Pierce, M. E.; Parsoms, R. L., Jr.; Radesca, L. A.; Lo, Y.
S.; Silvermamn, S.; Moore, J. R.; Islan, Q.; Choudhury,
A.; Fortunak, J. M. D.; Nguyen, D.; Luo, C.; Morgan, S.
J.; Davis, W. P.; Conalone, P. N. J. Org. Chem. 1998, 63,
8
536.

4938
M. A. P. Martins et al. / Tetrahedron Letters 45 (2004) 4935–4938
1
3
Pacholski, I. L.; Faoro, D.; Bonacorso, H. G.; Martins,
M. A. P. Synth. Commun. 2001, 31, 2855.
1. Zanatta, N.; Barichello, R.; Bonacorso, H. G.; Martins,
M. A. P. Synthesis 1999, 5, 765.
2. Bonacorso, H. G.; Bittencourt, S. R. T.; Lourega, R. V.;
Flores, A. F. C.; Zanatta, N.; Martins, M. A. P. Synthesis
C NMR (CDCl
(C3), 64.0 (C4).
Compound 3a, C10
3
, 100 MHz) d 164.3 (C2), 89.7 (C1), 71.7
2
2
H
6
Cl
2
O (M. wt 213.06); bp 85 ꢁC/
þ
2.3 mbar; CG-MS (EI 70 eV) m=z (%): 212 (M , 5), 129
(100), 101 (23), 77 (57), 51 (8);
1
H NMR (CDCl
(s, 1H, H1);
3
, 400 MHz) d 7.59–7.17 (m, 5H, Ph), 5.85
2000, 1.
1
3
2
3. (a) Bonacorso, H. G.; Bittencourt, S. R. T.; Wastowski, A.
D.; Wentz, A. P.; Zanatta, N.; Martins, M. A. P.
Tetrahedron Lett. 1996, 37, 9155; (b) Bonacorso, H. G.;
Bittencourt, S. R. T.; Wastowski, A. D.; Wentz, A. P.;
Zanatta, N.; Martins, M. A. P. J. Heterocycl. Chem. 1999,
C NMR (CDCl
3
, 100 MHz) d 173.8 (C2), 133.5, 132.0,
128.7, 118.8 (Ph), 97.9 (C3), 83.4 (C4), 70.0 (C1).
Compound 4a, C10 (M. wt 216.15); oil; CG-MS
7 3 2
H F O
þ
(EI 70 eV) m=z (%): 216 (M , 32), 187 (95), 129 (100), 108
(17), 77 (10);
1
36, 45.
H NMR (CDCl
3
3
, 400 MHz) d 7.45–7.22 (m, 5H, Ph);
1
2
4. Ziegler, G. R.; Welch, C. A.; Orzech, C. E.; Kikkawa, S.;
Miller, S. I. J. Am. Chem. Soc. 1963, 85, 1648.
5. Andrew, R. J.; Mellor, J. M. Tetrahedron 2000, 56, 7261.
6. (a) Ishii, S.; Yagi, K.; Umehara, T.; Kudo, M.; Nawa-
maki, T.; Watanabe, S. Japan Kokai, Tokkyo Koho JP 02,
C NMR (CDCl , 100 MHz) d 133.7–128.1 (Ph); 123.8
3
1
(C1, q, JC–F ¼ 289 Hz), 84.0 (C4), 82.1 (C3), 65.2 (C2, q,
2
2
2
J
Compound 4b, C
C–F ¼ 37 Hz).
4
H
3
F
3
O
2
(M. wt 140.05); oil; CG-MS (EI
þ
70 eV) m=z (%): 140 (M , 2), 136 (14), 108 (5), 55 (100);
1
129, 171. Chem. Abstr. 1990, 113, 17201a; (b) Buntain, I.
G.; Hatton, L. R.; Hawkins, D. W.; Pearson, C. J.;
Roberts, D. A. Eur. Pat. Appl. EP 295, 117. Chem. Abstr.
H NMR (CDCl
3
3
, 400 MHz) d 2.63 (s, 1H, H4);
1
1
C
NMR (CDCl 100 MHz) 126.8 (C1, q,
3
,
d
2
J
C–F ¼ 285 Hz), 77.3 (C3), 75.9 (C2, q,
JC–F ¼ 26 Hz),
1
990, 112, 35845n; (c) Moser, H.; Bohner, B.; Foery, W.
Eur. Pat. Appl. EP 268, 554; Chem. Abstr. 1988, 110,
3879; (d) Ishii, T.; Shimotori, H.; Tanaka, Y.; Ishikawa,
65.8 (C4).
Compound 4c, C
9
H
13
F
3
O
2
(M. wt 210.19); oil; CG-MS
þ
2
(EI 70 eV) m=z (%): 210 (M , 2), 153 (65), 141 (75), 71
(100);
K. Japan Kokai, Tokkyo Koho JP 01, 168, 675. Chem.
Abstr. 1989, 112, 35854; (e) Okada, I.; Yoshida, K.;
Sekine, K. Japan Kokai, Tokkyo Koho, JP 02, 292, 263.
Chem. Abstr. 1990, 114, 185497; (f) Sohn, E.; Handle, R.;
Mildenberger, H.; Buerstell, H.; Bauer, K.; Bieringer, H.
German Patent 3, 633, 840. Chem. Abstr. 1988, 110, 8202.
7. (a) Casida, J. E.; Pulman, D. A. In Advances in the
Chemistry of Insect Control III; Briggs, G. G., Ed.; Proc
1
3
H NMR (CDCl , 400 MHz) d 2.42 (t, 2H, H5), 2.19 (m,
2H, H6), 1.78 (m, 2H, H7), 1.43 (m, 2H, H8), 0.84 (t, 3H,
H9);
1
1
2
3
C
NMR (CDCl
3
,
100 MHz)
d
124.1 (C1, q,
J
J
C–F ¼ 285 Hz), 105.1 (C3), 91.6 (C4), 65.8 (C2, q,
2
C–F ¼ 26 Hz), 30.8 (C5), 26.7 (C6), 21.9 (C7), 18.4 (C8),
13.5 (C9).
3
rd Int. Symp. Adv. Chem. of Insect Control, Spec. Publ.
9 2
Compound 5a, C13H O N (M. wt 211.21); oil; CG-MS (EI
þ
1994, 147, p 36; (b) Bloomquist, J. R. In Biochemical Sites
70 eV) m=z (%): 211 (M , 33), 129 (100), 101 (9), 75 (19);
1
of Insecticide Action and Resistance; Ishaaya, I., Ed.;
Springer: Berlin, 2001; p 17; (c) Colliot, F.; Kukorowski,
K. A.; Hawkins, D. W.; Roberts, D. A. In Brighton Crop
Protection Conference—Pests and Diseases; British Crop
Protection Council: Farnham, UK, 1992; Vol. 1, p 29.
8. Penning, T. D.; Talley, J. J.; Bertenshaw, S. R.; Carter, J.
S.; Collins, P. W.; Docter, S.; Graneto, M. J.; Lee, L. F.;
Malecha, J. W.; Miyashiro, J. M.; Rogers, R. S.; Rogier,
D. J.; Yu, S. S.; Anderson, G. D.; Burton, E. G.; Cogburn,
J. N.; Gregory, S. A.; Koboldt, C. M.; Perkins, W. E.;
Seibert, K.; Veenhuizen, A. W.; Zhang, Y. Y.; Isakson, P.
C. J. Med. Chem. 1997, 40, 1347.
H NMR (CDCl
(s, 1H, H4), 2.22 (s, 3H, Me);
C NMR (CDCl , 100 MHz) d 168.2 (C6), 160.8 (C5),
3
3
, 400 MHz) d 7.43–7.25 (m, 5H, Ph), 6.35
1
3
160.0 (C3), 132.3–128.2 (Ph), 109.8 (C4), 84.8 (C7), 65.8
(C8), 18.9 (Me).
2
9 5 3
Compound 6a, C H Cl (M. wt 219.50); oil; CG-MS (EI
þ
70 eV) m=z (%): 218 (M , 43), 203 (100), 101 (57), 144 (36),
107 (19), 77 (17);
1
H NMR (CDCl
C NMR (CDCl
3
, 400 MHz) d 7.35–7.11 (5H, m, Ph);
, 100 MHz) d 132.0, 130.4, 128.3, 122.1
(Ph), 90.2 (C3), 86.7 (C2); 82.3 (C1).
Compound 6c, C (M. wt 213.54); oil; CG-MS (EI
1
3
3
8
H11Cl
3
þ
2
3
9. Linderman, R. J.; Lonicar, M. S. J. Org. Chem. 1988, 53,
70 eV) m=z (%): 213 (MH , 5), 141 (35), 129 (52), 95 (100),
71 (72);
6013.
1
0. Martins, M. A. P.; Beck, P.; Cunico, W.; Pereira, C. M. P.;
Sinhorin Blanco, R. F.; Peres; Bonacorso, H. G.; Zanatta,
N. Tetrahedron Lett. 2002, 43, 7005.
1. Compounds 2–8, were fully characterized by spectroscopy
methods, and satisfactory elemental analysis were ob-
tained: C ± 0.30, H ± 0.20; selected physical and spectral
data of the compounds 9, 10, are according to litera-
3
H NMR (CDCl , 400 MHz) d 2.41 (t, 2H, H4), 2.19 (m,
2H, H5), 1.58 (m, 2H, H6), 1.35 (m, 2H, H7), 0.89 (t, 3H,
H8);
1
3
3
C NMR (CDCl
(C3), 31.0 (C4), 27.1 (C5), 22.1 (C6), 18.7 (C7), 13.8 (C8).
3
, 100 MHz) d 93.4 (C1), 82.6 (C2), 69.6
Compound 7a, C
CG-MS (EI 70 eV) m=z (%): 136 (M , 100), 101 (43), 77
(38), 51 (29);
8
H
5
Cl (M. wt 136.58); bp 42 ꢁC/4 mbar;
þ
1
5c;17b;30
ture.
Compounds 2a,b and 3a did not show any IR bands on
the mOH region but presented mC@O at 1690, 1694 and
1
H NMR (CDCl
C NMR (CDCl
3
, 400 MHz) d 7.66–7.27 (5H, m, Ph);
, 100 MHz) d 132.9, 128.5, 128.3, 122.0
(Ph), 69.3 (C2), 67.3 (C1).
Compound 8a, C12 O (M. wt 224.18); oil; CG-MS (EI
1
3
3
ꢀ
1
1
697 cm , respectively.
Compound 2a, C10 Cl
2
H
5
3
O (M. wt 247.51); bp 120 ꢁC/
7 3
H F
þ
þ
.3 mbar; CG-MS (EI 70 eV) m=z (%): 246 (M , 10), 212
70 eV) m=z (%): 224 (M , 100), 155 (72), 102 (54), 77 (71),
51 (70);
(
2), 129 (100), 101 (90), 77 (99), 51 (90);
H NMR (CDCl
1
1
3
, 400 MHz) d 7.66–7.24 (m, 5H, Ph);
, 100 MHz) d 168.5 (C2), 133.6, 132.1,
28.8, 118.6 (Ph), 99.8 (C3), 95.3 (C1), 81.9 (C4).
H NMR (CDCl , 400 MHz) d 7.54–7.28 (m, 5H, Ph), 7.24
3
1
3
3
C NMR (CDCl
3
(d, 1H, H4,
3
J
H–H ¼ 16 Hz), 6.83 (d, 1H, H3,
100 MHz) 179.4 (C2, q,
1
J
C
J
H–H ¼ 16 Hz);
1
2
3
Compound 2b, C
4
HCl
3
O (M. wt 171.41); oil; CG-MS (EI
þ
NMR (CDCl
3
,
d
7
0 eV) m=z (%): 171 (MH , 5), 117 (100), 63 (85), 53 (20);
C–F ¼ 35 Hz), 132.8 (C3), 132.4–121.1 (Ph), 121.4 (C4),
1
1
H NMR (CDCl
3
, 400 MHz) d 2.09 (s, 1H, H4);
115.5 (C1, q, JC–F ¼ 289 Hz), 104.8 (C5), 87.1 (C6).