Synthesis and reactions of silylated and stannylated 1,2-azoles

Article abstract of DOI:10.1055/s-2001-17699

Silicon or tin 4-metalated pyrazoles and isoxazoles are synthesized by silyl- or stannylcupration from 4-haloazoles. On the other hand, 5-metalated pyrazoles are prepared by reaction of 5-un-substituted pyrazoles with LDA and subsequent treatment with chlorosilanes and chlorostannanes. Furthermore, starting from 5-unsubstituted 4-halopyrazoles and applying both methodologies, 4,5-dimetalated pyrazoles bearing silyl groups different from trimethylsilyl or tributylstannyl groups are obtained. Some regioselective ipso-substitutions are also studied.

Full text of DOI:10.1055/s-2001-17699

PAPER
1949
Synthesis and Reactions of Silylated and Stannylated 1,2-Azoles
S
ynthesis and Reaction
a
s of Silylat
r
ed
a
nd S
i
tannyla
o
ted 1,2-Azo
l
Departamento de Química Orgánica, Universidad de Valladolid, 47011 Valladolid, Spain
E-mail: agn@qo.uva.es
Received 29 June 2001; revised 7 August 2001
tributylstannyl chloride. Other methods, such as 1,3-dipo-
lar cycloadditions8–10 to metalated alkynes have also been
employed in the synthesis of silyl or stannyl pyrazoles and
isoxazoles.
Abstract: Silicon or tin 4-metalated pyrazoles and isoxazoles are
synthesized by silyl- or stannylcupration from 4-haloazoles. On the
other hand, 5-metalated pyrazoles are prepared by reaction of 5-un-
substituted pyrazoles with LDA and subsequent treatment with
chlorosilanes and chlorostannanes. Furthermore, starting from 5-
unsubstituted 4-halopyrazoles and applying both methodologies,
4,5-dimetalated pyrazoles bearing silyl groups different from trim-
ethylsilyl or tributylstannyl groups are obtained. Some regioselec-
tive ipso-substitutions are also studied.
In this paper we report an interesting alternative to silyla-
tion or stannylation of pyrazoles and isoxazoles. We have
synthesized, in good yields, silicon and tin 4-metalated
pyrazoles or isoxazoles and 5-metalated pyrazoles, as well
as 4,5-dimetalated pyrazoles, bearing silyl groups differ-
ent from the usual trimethylsilyl group. The 4-silyl and 4-
stannyl pyrazoles and isoxazoles are obtained from 4-ha-
loazoles by coupling with lithium silyl- or stannylcuprates
and the 5-metalated pyrazoles by lithiation with LDA in
TMEDA from 5-unsubstituted pyrazoles and subsequent
reaction with chlorosilanes or chlorostannanes. Moreover,
starting from 5-unsubstituted 4-halopyrazoles and using
LDA instead of BuLi, we have been able to introduce the
metalated groups in inverse order to that described by Ef-
fenberger.6 In this way we have synthesized differently
substituted 4,5-dimetalated pyrazoles in good yields.
Some regioselective ipso-substitutions of silyl and stannyl
groups are also described.
Key words: silylcupration, stannylcupration, silylated pyrazoles,
stannylated pyrazoles, silylated isoxazoles, stannylated isoxazoles
The easy and regioselective ipso-substitution of aryl
silanes1 and stannanes2 has led to considerable interest in
the development of methods which allow the introduction
of the silyl and stannyl groups directly into aromatic sub-
strates. We have focused our attention on the synthesis of
silylated and stannylated 1,2-azoles because the greatest
limitation of our earlier research into isoxazole and pyra-
zole chemistry was the difficulty in preparing a wide
range of functionalized 1,2-azoles. The general procedure
for making C–M (M = Si, Sn) bonds (coupling of R3MCl
with the corresponding Grignard or lithio derivative) has
been used for the synthesis of 4-trimethylsilyl- and 4-tri-
methylstannyl-3,5-dimethylisoxazoles.3,4 Nevertheless,
several attempts to prepare 5-trimethylsilyl-3,4-dimethyl-
isoxazole by treatment of 3,4-dimethylisoxazole with
BuLi or MeLi and Me3SiCl gave unsatisfactory results4
because of the very low stability of the intermediate 5-
lithioisoxazole.5 This methodology has also been em-
ployed successfully in the synthesis of silyl or stannyl
pyrazoles. Thus, Effenberger et al.6 prepared 4-trimethyl-
silyl-1-methylpyrazole by silylation of the Grignard de-
rivative from the 4-bromo-1-methylpyrazole and 5-
trimethylsilyl-1-methylpyrazole by silylation of the 5-
lithio derivative, resulting from lithiation of 1-meth-
ylpyrazole with BuLi, with chlorotrimethylsilane in good
yields. However, when they started from 4-bromo-1-me-
thylpyrazole and applied both procedures in this order for
We have prepared 4-dimethylphenylsilyl and 4-tributyl-
stannyl-3,5-dimethylisoxazole in good yields according
to the procedure used by other authors3,4 for introducing
the trimethylsilyl and trimethylstannyl group in the same
heterocycle.
This methodology involves a two-step sequence: halogen-
lithium exchange and coupling with chlorosilanes or chlo-
rostannanes (Scheme 1). The application of this method-
ology to the synthesis of 4-silylpyrazoles led to lower
yields (less than 20%, Tables 1 5a-c). However, this pro-
cedure provided good yields of the corresponding 4-stan-
nylpyrazoles (Tables 1, 6a-c). These results are in
accordance with the known higher electrophilicity of the
chlorostannanes with respect to the chlorosilanes. The re-
sults obtained are summarized in Table 1.
R3M
R2
X
CH3 1. BuLi, TMEDA
2. ClMR3
N
CH3
synthesizing
4,5-bis(trimethylsilyl)-1-methylpyrazole,
the yield of the second step was very low (12%). More re-
cently,7 4- and 5-tributylstannyl-1-phenylpyrazoles were
obtained by reaction of 4- and 5-lithio derivatives result-
ing from lithiation with BuLi of 4-bromo-1-phenylpyra-
zole and 1-phenylpyrazole, respectively, with
R
N
Z
Z
13-89%
1-2
3-6
Scheme 1 (X = Br, Z = O, NR; M = Si, Sn)
Our experience in the silyl and stannylcupration of other
organic substrates11 has been of great utility in the devel-
opment of a new method involving a single step, which
Synthesis 2001, No. 13, 08 10 2001. Article Identifier:
1437-210X,E;2001,0,13,1949,1958,ftx,en;E04301SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1950
M. Calle et al.
PAPER
Table 1 Reactions of 4-Haloazoles with BuLi + TMEDA and Chlorosilanes or Chlorostannanes (Scheme 1)
Substrate
R
X
Z
ClMR3
Temp (°C)
Product
Yield (%)
1
Me
Me
Me
Me
Me
Me
Ph
I
O
ClSiMe2Ph
ClSnBu3
–50
–50
–78
–78
–78
–78
–50
–78
0
0
0
0
0
0
0
0
3
70
72
19
89
17
78
13
73
1
I
O
4
2a
2a
2b
2b
2c
2c
Br
Br
Br
Br
Br
Br
NMe
NMe
NPh
NPh
NPh
NPh
ClSiMe2Ph
ClSnBu3
5a
6a
5b
6b
5c
6c
ClSiMe2Ph
ClSnBu3
ClSiMe2Ph
ClSnBu3
Ph
R3M2
has allowed us to obtain 4-silylpyrazoles with good
yields, even bearing the bulky tert-butyldiphenylsilyl
group. In this procedure the silyl or stannyl group is intro-
duced as a nucleophile by coupling of 4-haloazoles with
lithium silyl or stannylcuprates (Scheme 2). The results
are summarized in Table 2.
I
I
CH3
LDA,THF
CH3
CH3
R3M2(Me)CuLi
1.
R3M1
R3M1
N
N
N
2,ClM1R3
N
N
N
R1
12
R1
21-58%
R1
65-76%
15-20
13-14
Scheme 4
R3M
R2
R1
R1
X
R3M(Me)CuLi, -78
44-80%
0 ºC
Given that the syntheses of 4- or 5-metalated and 4,5-di-
metalated azoles were accomplished, some reactions of
the dimethylphenylsilyl and tributylstannyl group were
investigated since both groups are capable of undergoing
a variety of useful transformations.
R2
N
N
Z
Z
3-7
1-2
Scheme 2
The easy ipso-substitution of trimethylsilylazoles has al-
ready been demonstrated by Birkofer et al. who had car-
ried out the proto-, bromo- and nitrosodesilylation of
trimethylsilylpyrazoles12 and isoxazoles.13 They found
that the 3(5),4-bis(trimethylsilyl)pyrazole is protodesily-
lated exclusively in C-4 under acidic conditions, whereas
in basic medium it takes place only at the 3(5)-position.
More recently, Effenberger et al.6 confirmed the regiose-
lective electrophilic halo- and carbodesilylation in C-4
and the regioselective carbodesilylation in C-5 under nu-
cleophilic catalysis, starting from mono- and bis(trimeth-
ylsilyl)-1-methylpyrazoles.
The easy deprotonation in C-5 from 5-unsubstituted pyra-
zoles has allowed us to prepare 5-silyl- and 5-stannylpyra-
zoles via quenching with chlorosilanes and
chlorostannanes of the 5-lithium intermediate generated
by reaction with LDA in TMEDA (Scheme 3). The results
are summarized in Table 3.
This methodology could not be used for the synthesis of
5-silyl- or 5-stannylisoxazoles because the 5-lithioisox-
azole intermediate is opened by fission of N–O and C3–C4
bonds.5
Starting from 5-unsubstituted 4-halopyrazoles and using
both procedures previously cited we have synthesized 4,5-
dimetalated pyrazoles bearing different silyl and/or stan-
nyl groups (Scheme 4). The results are collected in
Table 4.
We have now verified that the behavior of the dimeth-
ylphenylsilyl group is analogous to that described for its
trimethylsilyl counterpart and have also carried out some
transformations in stannylazoles via electrophilic substi-
tution or Stille coupling.
The 4-benzoyl-1-phenyl-3,5-dimethylpyrazole (21) was
obtained from the corresponding dimethylphenylsi-
lylpyrazole (5b) by refluxing with benzoyl chloride. The
same compound, but with a slightly better yield, was pre-
pared starting from the analogous 4-stannyl pyrazole 6b.
However, when the benzoylation of the hindered 4-tert-
butyldiphenylsilylpyrazole 7b was carried out the yield
was low. Under the same conditions (or in the presence of
aluminum chloride) desilylative and destannylative acety-
CH3
CH3
LDA,THF
TMEDA
CH3
R3MCl
Li
N
R3M
H
N
N
N
N
N
35-83%
R1
R1
R1
9-11
8
Scheme 3
Synthesis 2001, No. 13, 1949–1958 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis and Reactions of Silylated and Stannylated 1,2-Azoles
1951
Table 2 Reactions of 4-Haloazoles with Mixed Lithium Silyl or Stannylcuprates (Scheme 2)
Substrate
R1
R2
X
Z
MR3
Product
3
Yield (%)
1
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
Me
Me
Me
Me
Me
Me
Me
Ph
I
O
SiMe2Ph
SiMe2Ph
SnBu3
80
78
81
54
71
68
44
78
62
50
79
2a
2a
2a
2b
2b
2b
2c
2c
2c
2d
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
NMe
NMe
NMe
NPh
NPh
NPh
NPh
NPh
NPh
NMe
5a
6a
SiPh2Bu-t
SiMe2Ph
SnBu3
7a
5b
6b
7b
5c
SiPh2Bu-t
SiMe2Ph
SnBu3
Ph
6c
Ph
SiPh2Bu-t
SiMe2Ph
7c
Me
5d
Table 3 Synthesis of 5-Silyl- or 5-Stannylpyrazoles by the Reac-
tion of 5-Unsubstituted Pyrazoles with LDA and Chlorosilanes or
Chlorostannanes (Scheme 3)
al.7 to convert the 4-tributylstannyl-1-phenylpyrazole to
the 4-benzoyl-1-phenylpyrazole. This result is important
because repeated attempts to effect the Friedel–Crafts re-
action in the isoxazole series had failed.14 Palladium-cat-
alyzed acetylation of 4-stannylpyrazoles did not take
place either (Scheme 6).
Substrate
R1
ClMR3
Product
9a
Yield (%)
8a
8a
8b
8b
8b
Me
Me
Ph
Ph
Ph
ClSiMe2Ph
ClSnBu3
ClSiMe2Ph
ClSnBu3
79
83
75
80
35
10a
9b
R
Bu3Sn
H3C
CH3
CH3
O
RCOCl
H3C
N
N
10b
Z
Z
Pd(PPh3 )2Cl2
ClSiPh2Bu-t 11b
22 (45%); Z=O, R=Ph
3, Z=O
6b; Z=NPh
21 (69%); Z=NPh, R=Ph
Scheme 6
lation or ethoxycarbonylation did not occur. The reactivi-
ty of benzoyl chloride, as compared to acetyl or The transformation of the dimethylphenylsilyl group into
ethoxycarbonyl chloride, can be attributed to the higher cyano is even more interesting, because it is impossible to
boiling point of the former, thereby permitting the attain- introduce it directly into the pyrazole ring. The 4-dimeth-
ment of a higher reaction temperature (Scheme 5).
ylphenylsilyl-1,3,5-trimethylpyrazole (5a) afforded in
good yield the corresponding 4-cyanopyrazole 23 by hy-
drolysis of the intermediate formed in its reaction with
chlorosulfonyl isocyanate (Scheme 7).
R
R3M
H3C
CH3
CH3
O
RCOCl
reflux
H3C
N
N
N
N
PhMe 2Si
H3C
NC
H3C
CH3
CH3
1. ClSO2N=C=O
2. HCl
Ph
Ph
N
N
5b; MR3= SiMe2Ph
6b; MR3=SnBu3
21 (52%); R=Ph
21 (58%); R=Ph
N
N
72%
CH3
5a
CH3
7b; MR3=SiPh2But
21 (12%); R=Ph
23
Scheme 5
Scheme 7
Moreover, we were able to prepare 4-benzoyl-3,5-dimeth-
ylisoxazole (22) from 4-tributylstannyl-3,5-dimethylisox-
azole (3) by palladium-catalyzed coupling with benzoyl
chloride, according to the procedure used by Yamanaka et
The electrophilic substitution in 5-silyl or 5-stannylazoles
is more difficult. Repeated attempts to convert these met-
alated groups into benzoyl, acetyl, ethoxycarbonyl and
cyano groups, by the same procedures used for the C-4
Synthesis 2001, No. 13, 1949–1958 ISSN 0039-7881 © Thieme Stuttgart · New York

1952
M. Calle et al.
PAPER
Table 4 Synthesis of 4,5-Dimetalated Pyrazoles (Scheme 4)
Substrate
12a
R1
M1R3
Product
13a
13b
13b
13b
14
Yield (%)
M2R3
Product
15a
16
Yield (%)
Me
Ph
Ph
Ph
Ph
Ph
Ph
SiMe2Ph
SiMe2Ph
SiMe2Ph
SiMe2Ph
SnBu3
76
73
–
SnBu3
43
55
51
33
41
58
21
12b
SiMe2Ph
SnBu3
12b
15b
17
12b
–
SiPh2Bu-t
SnBu3
12b
65
–
18
12b
SnBu3
14
SiMe2Ph
SiPh2Bu-t
19
12b
SnBu3
14
–
20
substitution, proved unsuccessful. Palladium-catalyzed
coupling of 5-stannylpyrazoles with benzoyl chloride did
not take place either. Only the halogenation occurred and
the stannyl group was shown to be more reactive than the
silyl group, probably due to the low energy and high po-
larizability of the Sn–C bond. Thus, 4-bromo- or 4-iodo-
1,3-dimethyl-5-dimethylphenylsilylpyrazole 24 or 13a
was obtained, starting from 1,3-dimethyl-5-dimethyl phe-
nylsilylpyrazole (9a) by reaction with one equivalent of
CH3
CH3
HO
Ph
PhCHO, CsF, DMF
82%
PhMe 2Si
N
N
N
N
Ph
Ph
9b
27
Scheme 9
bromine or iodine, respectively. The 4-bromo compound transformation in 4-dimethylphenylsilylpyrazoles using
24 was quickly converted into the 4,5-dibromopyrazole tetrafluoroboric acid etherate as an electrophile, the pro-
25 with a quantitative yield by addition of another equiv- todesilylation was faster than the phenyl-fluoro substitu-
alent of bromine. However, the treatment of 5-tributyl- tion
(Scheme 10).
However,
when
the
stannyl-3-methyl-1-phenylpyrazole (10b) with one dimethylphenylsilyl group is attached to C-5 we were able
equivalent of iodine afforded the 5-iodopyrazole 26 re- to isolate and identify the fluoro-dimethylphenylsi-
sulting from the iodo-destannylation, exclusively lylpyrazole 29, which was easily oxidized to the 5-pyra-
(Scheme 8).
zolone 30 (Scheme 10).
X
CH3
PhMe 2Si
CH3
CH3
X2
X
CH3
X2
H
CH3
PhMe 2Si
N
PhMe 2Si
X
N
N
N
HBF4 OEt2
90%
Ph
N
Ph
N
N
N
N
N
X=Br
X=Br,I
CH3
25 (96%); X=Br
CH3
CH3
Ph
2c
Ph
24 (92%): X=Br
13a (95%); X=I
9a
28
CH3
CH3
CH3
CH3
HBF4 OEt2
50%
FMe2 Si
PhMe 2Si
I2
N
N
Bu3Sn
I
N
N
N
N
N
N
90%
Ph
Ph
9b
Ph
Ph
CH3
N
29
10b
26
MCPBA, KF,DMF
58%
O
N
Scheme 8
Ph
30
Although the Friedel–Crafts carbodesilylation of 5-silyl
pyrazoles did not take place, it was possible to convert the
dimethylphenylsilyl in a hydroxybenzyl group by fluo-
ride-catalyzed reaction with benzaldehyde6 (Scheme 9).
Scheme 10
In conclusion, we have described an efficient methodolo-
gy to prepare silyl or tin 4-metalated azoles (pyrazoles and
isoxazoles), 5-metalated and 4,5-dimetalated pyrazoles,
bearing silyl groups different from the usual trimethylsi-
lyl. Although the azoles bearing the bulky tert-butyldiphe-
The dimethylphenylsilyl group has an additional advan-
tage. According to Fleming et al.15 it can be converted into
a hydroxyl group by reaction with an electrophile with the
aim of changing the phenyl group in a better leaving group
followed by oxidation with a peracid. When we tried this
Synthesis 2001, No. 13, 1949–1958 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis and Reactions of Silylated and Stannylated 1,2-Azoles
1953
13C NMR: = 173.51, 164.99, 105.98, 29.23, 27.19, 13.57, 13.14,
11.01, 9.48.
nylsilyl group have little interest because they were
obtained in low yields and this hindered group was shown
to be practically unreactive toward the electrophilic sub- MS (EI): m/z (%) = 387(M+, 1), 330 (30), 274 (24), 216 (38), 80
(59), 41 (100).
stitution, the dimethylphenylsilyl is a very interesting
group. We have proved that this silyl group imparts a very
similar reactivity to that known for the trimethylsilyl
group. Moreover, the dimethylphenylsilyl group has an
advantage over the trimethylsilyl group in that the dime-
thylphenylsilyl group can be oxidized to a hydroxyl group
allowing us to convert 5-dimethylphenylsilylpyrazoles
into 5-pyrazolones.
Anal. Calcd for C17H33NOSn: C, 52.87; H, 8.61; N, 3.63. Found: C,
53.06; H, 8.83; N, 3.42.
1,3,5-Trimethyl-4-dimethylphenylsilylpyrazole (5a)
Colorless oil; yield: 0.04 g (19%); Rf 0.33 (hexane–EtOAc, 5:1).
IR (CCl4): 1540, 1520, 1440, 1250, 1100 cm–1.
1H NMR: = 7.50 (m, 2 H), 7.36 (m, 3 H), 3.71 (s, 3 H), 2.18 (s, 3
H), 2.08 (s, 3 H), 0.52 s, 6 H).
13C NMR: = 152.80, 144.98, 139.48, 133.84, 128.86, 127.76,
106.91, 35.48, 15.00, 11.95, –0.57.
MS (EI): m/z (%) = 244 (M+, 24), 229 (100), 167 (12), 135 (8), 77
THF was distilled from sodium benzophenone ketyl in a recycling
still. CH2Cl2 was distilled from P2O5. All chromatographic and
workup solvents were distilled prior to use. CuCN was dried in vac-
uo over P2O5. The starting 4-haloazoles 1, 2a–d and 12a–b were ob-
tained by bromination16 or iodination17 from corresponding
pyrazoles and isoxazoles. Mixed phenyldimethylsilyl(methyl)cu-
prate,18 tert-butyldiphenylsilyl(methyl)cuprate19 and tributylstannyl
(methyl)cuprate20 were used, because they have some advantages.
Only a silyl or stannyl group is needed and the by-product methane
of the silyl or stannylcupration step is volatile. All reactions involv-
(10), 43 (18).
Anal. Calcd for C14H20N2Si: C, 68.80; H, 8.25; N, 11.46. Found: C,
68.54; H, 8.57; N, 11.7.
3,5-Dimethyl-4-dimethylphenylsilyl-1-phenylpyrazole (5b)
Colorless oil; yield: 0.05 g (17%); Rf 0.29 (hexane–EtOAc, 5:1).
IR (neat): 1590, 1550, 1250, 1100 cm–1.
ing organometallic reagents were carried out under N2. 1H and 13
C
NMR spectra were recorded at 300 MHz and 75 MHz, respectively
in CDCl3 as an internal standard. Carbon multiplicities were as-
signed by DEPT experiments. Reactions were monitored by TLC
on a pre-coated plate of silica gel 60 (nano-SIL-20, Macheray-Na-
gel). Flash chromatography was performed on silica gel 60 (230–
400 mesh, M-N).
H NMR: = 7.58 (m, 2 H), 7.39 (m, 8 H), 2.22 (s, 3 H), 2.15 (s, 3
H), 0.59 (s, 6 H).
13C NMR: = 154.98, 145.36, 139.48, 139.40, 133.88, 128.93,
127.82, 127.54, 125.48, 124.62, 108.50, 15.20, 13.26, –0.60.
MS (EI): m/z (%) = 306 (M+, 31), 291 (100), 276 (3), 229 (5), 135
(5), 105 (10), 77 (15).
Halogen–Lithium Exchange in 4-Haloazoles and Reactions with
Chlorosilanes and Chlorostannanes; General Procedure
To a dry flask with magnetic stirrer were added anhyd THF (4 mL),
TMEDA (0.18 mL, 1.2 mmol) and 4-haloazole 1,2 (1 mmol). The
solution was cooled to –78 °C or –50 °C and BuLi (0.75 mL, 1.6 N,
1.2 mmol) was added via syringe. The reaction was stirred at this
temperature for 5 h and dimethylphenylchlorosilane or tributylchlo-
rostannane (1 mmol) was added in THF (1 mL). The mixture was
stirred for 1 h and then was slowly allowed to warm to r.t. until TLC
indicated complete reaction. Quenching with an aq NH4Cl solution,
workup with Et2O, drying of the Et2O layer (MgSO4) and chroma-
tography of the residue obtained after evaporation of Et2O gave the
following products.
Anal. Calcd for C19H22N2Si: C, 74.46; H, 7.24; N, 9.14. Found: C,
74.74; H, 6.93; N, 8.87.
3-Methyl-4-dimethylphenylsilyl-1,5-diphenylpyrazole (5c)
Colorless oil; yield: 0.04 g (13%); Rf 0.24 (hexane–EtOAc, 5:1).
IR (neat): 1650, 1600, 1550, 1260, 1100 cm–1.
1H NMR: = 7.62 (m, 2 H), 7.41–7.20 (m, 13 H), 2.40 (s, 3 H), 0.33
(s, 6 H).
13C NMR: = 148.35, 140.57, 139.64, 139.52, 138.81, 133.42,
132.94, 129.74, 129.30, 128.73, 128.31, 127.66, 127.59,
124.61,107.89, 12.40, –0.06.
MS (EI): m/z (%) = 368 (M+, 38), 353 (43), 275 (100), 219 (12), 135
(11), 105 (8), 77 (6).
3,5-Dimethyl-4-dimethylphenylsilylisoxazole (3)
Colorless oil; yield: 0.16 g (70%); Rf 0.42 (CH2Cl2).
IR (neat): 1580, 1470, 1240, 1100 cm–1.
Anal. Calcd for C24H24N2Si: C, 78.21; H, 6.56; N, 7.60. Found: C,
77.91; H, 6.73; N, 7.28.
1H NMR: = 7.48 (m, 2 H), 7.33 (m, 3 H), 2.23 (s, 3 H), 2.11 (s, 3
H), 0.54 (s, 6 H).
13C NMR: = 167.30, 159.41, 139.52, 132.92, 129.22, 127.94,
104.79, 11.17, 10.17, 0.73.
MS (EI): m/z (%) = 231 (M+, 10), 216 (47), 135 (7), 77 (10), 43
(100).
4-Tributylstannyl-1,3,5-trimethylpyrazole (6a)
Colorless oil; yield: 0.35 g (89%); Rf 0.42 (CH2Cl2).
IR (neat): 1640, 1550, 1410 cm–1.
1H NMR: = 3.75 (s, 3 H), 2.21 (s, 3 H), 2.19 (s, 3 H), 1.65 (m, 6
H), 1.45 (m, 12 H), 0.90 (t, J = 7.2 Hz, 9 H).
13C NMR: = 145.68, 138.4, 104.89, 36.80, 27.93, 26.80, 17.47,
13.56, 12.12, 10.23.
Anal. Calcd for C13H17NOSi: C, 67.49; H, 7.41; N, 6.05. Found: C,
67.56; H, 7.11; N, 6.36.
MS (EI): m/z (%) = 400 (M+, 1), 343 (22), 315 (8) 269 (32), 109
(22), 43 (40), 41 (100).
4-Tributylstannyl-3,5-dimethylisoxazole (4)
Colorless oil; yield: 0.27 g (72%); Rf 0.44 (CH2Cl2).
IR (neat): 1570, 1440 cm–1.
Anal. Calcd for C18H36N2Sn: C, 54.16; H, 9.09; N, 7.02. Found: C,
53.89; H, 9.32; N, 6.81.
1H NMR: = 2.36 (s, 3 H), 2.23 (s, 3 H), 1.48 (m, 6 H), 1.32 (m, 12
H), 0.89 (t, J = 7.1 Hz, 9 H).
Synthesis 2001, No. 13, 1949–1958 ISSN 0039-7881 © Thieme Stuttgart · New York

1954
M. Calle et al.
PAPER
4-Tributylstannyl-3,5-dimethyl-1-phenylpyrazole (6b)
4-Tributylstannyl-3,5-dimethyl-1-phenylpyrazole (6b)
Colorless oil; yield: 0.36 g (78%); Rf 0.40 (CH2Cl2).
Yield: 1.24 g (68%).
IR (neat): 1630,1580, 1540, 1490 cm–1.
1H NMR: = 7.50– 7.30 (m, 5 H), 2.32 (s, 3 H), 2.30 (s, 3 H), 1.62
4-Tributylstannyl-3-methyl-1,5-diphenylpyrazole (6c)
Yield: 1.28 g (62%).
(m, 6 H), 1.32 (m, 12 H), 0.91 (t, J = 7.1 Hz, 9 H).
13C NMR: = 148.70, 139.62, 137.25, 128.98, 127.60, 124.51,
106.20, 29.12, 27.85, 18.20, 13.45, 12.17 and 11.56.
4-tert-Butyldiphenylsilyl-1,3,5-trimethylpyrazole (7a)
Colorless oil; yield: 0.72 g (54%); Rf 0.30 (hexane–EtOAc, 10:1).
IR (CHCl3): 1610, 1590, 1540, 1380, 1360, 1100 cm–1.
MS(EI): m/z (%) = 462 (M+, 0.5), 405 (5), 342 (26), 328 (10), 269
1H NMR: = 7.64 (m, 4 H), 7.47 (m, 6 H), 3.73 (s, 3 H), 2.22 (s, 3
H), 2.20 (s, 3 H), 1.09 (s, 9 H).
13C NMR: = 153.29, 144.55, 135.69, 133.86, 129.76, 127.86,
103.68, 36.61, 27.47, 18.97, 10.96, 10.16.
MS (EI): m/z (%) = 348 (M+, 1), 291 (68), 213 (100), 77 (18), 57
(52).
(32), 171(22), 105 (10), 77 (100).
Anal. Calcd for C23H38N2Sn: C, 59.89; H, 8.30; N, 6.07. Found: C,
60.02; H, 8.53; N, 6.34.
4-Tributylstannyl-3-methyl-1,5-diphenylpyrazole (6c)
Colorless oil; yield: 0.38 g (73%); Rf 0.36 (hexane–EtOAc, 10:1).
IR (neat): 1580, 1530, 1490 cm–1.
1H NMR: = 7.38– 7.20 (m, 10 H), 2.38 (s, 3 H), 1.72 (m, 6 H), 1.36
Anal. Calcd for C22H28N2Si: C, 75.81; H, 8.10; N, 8.04: Found: C,
76.18; H, 8.41; N, 7.81.
(m, 12 H), 0.91 (t, J = 7.0Hz, 9 H).
13C NMR: = 149.63, 144.52, 140.56, 130.66, 128.54, 128.32,
128.09, 127.98, 126.95, 124.59, 105.48, 27.78, 26.79, 17.44, 13.56,
12.46.
MS (EI): m/z (%) = 524 (M+, 2), 467 (14), 379 (20), 342 (26), 269
(32), 248 (22), 233 (10), 77 (48), 41 (100).
4-tert-Butyldiphenylsilyl-3,5-dimethyl-1-phenylpyrazole (7b)
Colorless oil; yield: 0.72 g (44%); Rf 0.53 (hexane–EtOAc, 5:1).
IR (neat): 1600, 1550, 1500, 1380, 1360, 1100 cm–1.
1H NMR: = 7.75 (m, 5 H), 7.41 (m, 10 H), 2.33 (s, 3 H), 2.32 (s,
3 H), 1.10 (s, 9 H).
13C NMR: = 147.54, 139.75, 136.61, 135.12, 134.77, 129.63,
129.14, 127.78, 127.69, 124.64, 106.33, 26.52, 18.99, 12.35, 11.47.
Anal. Calcd for C28H40N2Sn: C, 64.26; H, 7.70; N, 5.35. Found: C,
63.92; H, 7.34; N, 5.01.
MS (EI): m/z (%) = 410 (M+, 0.8), 353 (100), 333 (11), 275 (68), 77
(27), 57 (71).
Silyl- or Stannylcupration of 4-Halopyrazoles and Isoxazoles;
General Procedure
To a stirred solution of lithium dimethylphenylsilyl(methyl)-, tert-
butyldiphenylsilyl(methyl)- or tributylstannyl(methyl)cuprate (4
mmol) in THF (10 mL) at –78 °C was added the 4-haloazoles 1,2 (4
mmol) and the mixture stirred under N2 at –78 °C for 30 min. The
mixture was slowly allowed to warm to 0 °C and stirred at that tem-
perature until the TLC indicated complete reaction. Quenching at 0
°C with an aq NH4Cl soln, workup with Et2O, drying of the Et2O
layer (MgSO4) and chromatography of the residue obtained after
evaporation of Et2O gave the following products.
Anal. Calcd for: C27H30N2Si: C, 78.97; H, 7.36; N, 6.82. Found: C,
79.23; H, 6.98; N, 6.54.
4-tert-Butyldiphenylsilyl-3-methyl-1,5-diphenylpyrazole (7c)
Colorless oil; yield: 0.92 g (50%); Rf 0.32 (hexane–EtOAc, 10:1).
IR (neat): 1640, 1600, 1530, 1390, 1370, 1100 cm–1.
1H NMR: = 7.70 (m, 7 H), 7.43–7.21 (m, 13 H), 2.47 (s, 3 H), 1.15
(s, 9 H).
13C NMR: = 148.44, 140.08, 139.63, 136.89, 135.20, 135.00,
129.79, 129.50, 128.76, 128.36, 127.75, 127.60, 127.26, 124.70,
106.84, 26.50, 18.93, 12.42.
3,5-Dimethyl-4-dimethylphenylsilylisoxazole (3)
Yield: 0.72 g (80%).
MS (EI): m/z (%) = 472 (M+, 2), 415 (73), 233 (100), 183 (43), 105
(22), 77 (18), 57 (28).
1,3,5-Trimethyl-4-dimethylphenylsilylpyrazole (5a)
Yield: 0.76 g (78%).
Anal. Calcd for C32H32N2Si: C, 81.31; H, 6.82; N, 5.93. Found: C,
81.58; H, 7.03; N, 6.12.
3,5-Dimethyl-4-dimethylphenylsilyl-1-phenylpyrazole (5b)
Yield: 0.84 g (71%).
5-Silyl and 5-Stannylpyrazoles; General Procedure
To a stirred mixture of LDA (3 mmol) [prepared from diisopropy-
lamine (300 mg, 3 mmol) in THF (10 mL) and BuLi (182 mg, 3
mmol, 1.6 M in hexane, 1.87 mL) at –20 °C] and TMEDA (418 mg,
3.6 mmol), cooled to –78 °C was added the 5-unsubstituted pyra-
zole 8 (3 mmol) dissolved in THF (3 mL). The mixture was kept un-
der N2 at –78 °C for 1 h, then added to the chlorosilane or
chlorostannane (3 mmol), allowed to warm slowly to r.t. and stirred
at this temperature for 1 h except for the tert-butyldiphenylchlorosi-
lane (5 h). The mixture was hydrolyzed with an aq NH4Cl solution,
extracted with Et2O and the Et2O layer was dried (MgSO4). Et2O
was evaporated and the residue was chromatographed to give the
following compounds.
3-Methyl-4-dimethylphenylsilyl-1,5-diphenylpyrazole (5c)
Yield: 1.12 g (78%).
1,5-Dimethyl-4-dimethylphenylsilylpyrazole (5d)
Colorless oil; yield: 0.72 g (79%); Rf 0.27 (hexane–EtOAc, 10:1).
IR (neat): 1650, 1550, 1500, 1250, 1100 cm–1.
1H NMR: = 7.50 (m, 2 H), 7.35 (m, 3 H), 7.15 (s, 1 H), 3.81 (s, 3
H), 2.18 (s, 3 H), 0.48 (s, 6 H).
13C NMR: = 153.66, 138.59, 137.16, 133.77, 128.95, 127.72,
110.59, 38.01, 14.44, -1.67.
MS (EI): m/z (%) = 230 (M+, 21), 215 (100), 153 (4), 135 (8), 43 (2).
Anal. Calcd for C13H18N2Si: C, 67.77; H, 7.88; N, 12.16. Found: C,
67.45; H, 7.54; N, 11.83.
1,3-Dimethyl-5-dimethylphenylsilylpyrazole (9a)
Colorless oil; yield: 0.54 g (79%); Rf 0.28 (hexane–EtOAc, 10:1).
IR (neat): 1580, 1500, 1470, 1270, 1100 cm–1.
4-Tributylstannyl-1,3,5-trimethylpyrazole (6a)
Yield: 1.28 g (81%).
Synthesis 2001, No. 13, 1949–1958 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis and Reactions of Silylated and Stannylated 1,2-Azoles
1955
1H NMR: = 7.73 (m, 2 H), 7.39 (m, 3 H), 6.21 (s, 1 H), 3.68 (s, 3
H), 2.29 (s, 3 H), 0.58 (s, 6 H).
13C NMR: = 147.38, 141.22, 136.24, 133.80, 129.54, 127.99,
115.24, 39.23, 12.90, 0.76.
MS (EI): m/z (%) = 230 (M+, 19), 215 (38), 183 (26), 135 (46), 105
(38), 95 (5), 77 (100).
4,5-Dimetalated Pyrazoles; General Procedure
Starting from 5-unsubstituted 4-iodopyrazoles and using the same
procedure described above the following 5-silyl or 5-stannyl-4-io-
dopyrazoles were prepared. The silyl or stannylcupration of 13a,
13b or 14 by the procedure earlier described afforded the 4,5-dimet-
alated pyrazoles 15–20.
4-Iodo-1,3-dimethyl-5-dimethylphenylsilylpyrazole (13a)
Colorless oil; yield: 1.08 g (76%); Rf 0.33 (hexane–EtOAc, 10:1).
Anal. Calcd for C13H18N2Si: C, 67.77; H, 7.88; N, 12.16. Found: C,
68.02; H, 8.03; N, 11.85.
IR (neat): 1640, 1590, 1480, 1250, 1110 cm–1.
1H NMR: = 7.52 (m, 2 H), 7.49 (m, 3 H), 3.63 (s, 3 H), 2.26 (s, 3
H), 0.76 (s, 6 H).
13C NMR: = 150.48, 141.04, 136.34, 133.84, 129.67, 128.12,
71.09, 40.89, 13.61, –0.60.
MS (EI): m/z(%) = 356 (M+, 24), 341 (25), 279 (3), 229 (100), 199
3-Methyl-5-dimethylphenylsilyl-1-phenylpyrazole (9b)
Colorless oil; yield: 0.63 g (75%); Rf 0.34 (hexane–EtOAc), 10:1).
IR (neat): 1640, 1590, 1520, 1250, 1100 cm–1;
1H NMR: = 7.56–7.19 (m, 10 H), 6.39 (s, 1 H), 2.37 (s, 3 H), 0.33
(s, 6 H).
13C NMR: = 148.97, 142.47, 142.02, 137.13, 133.74, 132.88,
129.31, 128.51, 127.80, 125.68, 117.12, 13.01, –2.22.
MS (EI): m/z (%) = 292 (M+, 50), 277 (35), 199 (100), 158 (18), 135
(27), 135 (17), 105 (35), 77 (31), 43 (78).
Anal. Calcd for C13H17IN2Si: C, 43.83; H, 4.81; N, 7.86. Found: C,
44.17; H, 5.12; N, 8.07.
(14), 105 (35), 77 (38).
4-Iodo-3-methyl-5-dimethylphenylsilyl-1-phenylpyrazole (13b)
Colorless crystals; yield: 1.22 g (73%); mp 86–88 °C (hexane);
Rf 0.45 (hexane–EtOAc, 10:1).
Anal. Calcd for C18H20N2Si: C, 73.92; H, 6.89; N, 9.58. Found: C,
74.12; H, 6.58; N, 9.75.
IR (CCl4): 1630, 1580, 1500, 1250, 1100 cm–1.
1H NMR: = 7.48 (m, 2 H), 7.31 (m, 6 H), 7.18 (m, 2 H), 2.37 (s, 3
H), 0.38 (s, 6 H).
13C NMR: = 151.86, 142.53, 142.03, 136.47, 133.72, 129.18,
128.54, 128.48, 127.69, 126.76, 73.52, 13.72, –0.97.
5-Tributylstannyl-1,3-dimethylpyrazole (10a)
Colorless oil; yield: 0.96 g (83%); Rf 0.31 (hexane–EtOAc, 5:1).
IR (neat): 1650, 1600, 1540 cm–1.
1H NMR: = 6.02 (s, 1 H), 3.86 (s, 3 H), 2.29 (s, 3 H), 1.68 (m, 6
H), 1.45 (m, 12 H), 0.92 (t, J = 7.1 Hz, 9 H).
13C NMR: = 148.12, 142.92, 114.50, 40.15, 29.80, 17.46, 13.56,
13.10, 10.09.
MS (EI): m/z (%) = 386 (M+, 2), 329 (42), 271 (40), 215 (100), 174
MS (EI): m/z (%) = 418 (M+, 19), 325 (50), 291 (100), 135 (12), 105
(15), 77 (53).
Anal. Calcd for C18H19IN2Si: C, 51.68; H, 4.58; N, 6.70. Found: C,
51.33; H, 4.89; N, 7.02.
(78).
Anal. Calcd for C17H34N2Sn: C, 53.01; H, 8.90; N, 7.27. Found: C,
52.86; H, 9.14; N, 7.51.
5-Tributylstannyl-4-iodo-3-methyl-1-phenylpyrazole (14)
Colorless oil; yield: 1.49 g (65%); Rf 0.46 (hexane– EtOAc, 10:1).
IR (neat): 1590, 1490, 1440 cm–1.
1H NMR: = 7.43–7.34 (m, 5 H), 2.34 (s, 3 H), 1.36 (m, 6 H), 1.21
(m, 6 H), 0.93 (t, J = 7.1 Hz, 6 H), 0.82 (t, J = 7.0 Hz, 9 H).
13C NMR: = 150.97, 139.60, 139.21, 133.72, 129.58, 128.80,
72.26, 33.58, 31.78, 22.46, 14.16, –0.58.
5-Tributylstannyl-3-methyl-1-phenylpyrazole (10b)
Colorless oil; yield: 1.07 g (80%); Rf 0.36 (hexane–EtOAc, 10:1).
IR (neat): 1650, 1580, 1500 cm–1.
1H NMR: = 7.41 (m, 3 H), 7.38 (m, 2 H), 6.25 (s, 1 H), 2.37 (s, 3
H), 1.43 (m, 6 H), 1.23 (m, 12 H), 0.91 (t, J = 7.0 Hz, 9 H).
13C NMR: = 149.95, 143.32, 143.04, 128.92, 127.20, 124.27,
116.62, 28.87, 27.10, 13.53, 13.25, 10.74.
MS (EI): m/z (%) = 448 (M+, 3), 391 (86), 335 (33), 277 (100), 236
MS (EI): m/z (%) = 574 (M+, 2), 517 (27), 461 (8), 403 (23), 276 (5),
77 (19), 57 (40), 41 (100).
Anal. Calcd for C22H35IN2Sn: C, 46.10; H, 6.16; N, 4.89. Found: C,
46.47; H, 6.48; N, 5.18.
(58), 57 (28).
Anal. Calcd for C22H36N2Sn: C, 59.08; H, 8.11; N, 6.26. Found: C,
58.87; H, 8.36; N, 5.94.
4-Tributylstannyl-1,3-dimethyl-5-dimethylphenylsilylpyrazole
(15a)
Colorless oil; yield: 0.68 g (43%); Rf 0.42 (hexane–EtOAc, 10:1).
5-tert-Butyldiphenylsilyl-3-methyl-1-phenylpyrazole (11b)
IR (neat) 1630, 1590, 1500, 1480, 1250,1100 cm–1.
1H NMR: = 7.46–7.21 (m, 5 H), 3.85 (s, 3 H), 2.31 (s, 3 H), 1.55
Colorless oil; yield: 0.41 g (35%); Rf 0.30 (hexane–EtOAc, 10:1).
IR (neat): 1640, 1530, 1500, 1380, 1365, 1100 cm–1.
1H NMR: = 7.79–7.29 (m, 15 H), 6.81 (s, 1 H), 2.48 (s, 3 H), 1.12
(s, 9 H).
13C NMR: = 149.03, 142.03, 138.56, 134.76, 133.26, 129.42,
129.32, 127.82, 127.56, 126.38, 118.86, 26.51, 19.93, 13.26.
(m, 6 H), 1.42 (m, 12 H), 0.95 (t, J = 7.1 Hz, 9 H), 0.38 (s, 6 H).
13C NMR: = 142.55, 139.74, 135.01, 132.12, 129.38, 127.50,
106.87, 38.53, 29.61, 16.48, 14.03, 11.55, 9.83, 0.90.
MS (EI): m/z (%) = 520 (M+, 1), 463 (34), 385 (42), 328 (7), 271
(100), 135 (10), 57 (45).
MS (EI) m/z (%) = 396 (M+, 4), 339 (70), 261 (100), 105 (25), 77
(14), 57 (46).
Anal.Calcd for C25H44N2SiSn: C, 57.81; H, 8.54; N, 5.39. Found: C,
57.46; H, 8.71; N, 5.09.
Anal. Calcd for C26H28N2Si: C, 78.74; H, 7.12; N, 7.06. Found: C,
78.41; H, 6.95; N, 7.38.
Synthesis 2001, No. 13, 1949–1958 ISSN 0039-7881 © Thieme Stuttgart · New York

1956
M. Calle et al.
PAPER
4-Tributylstannyl-3-methyl-5-dimethylphenylsilyl-1-
phenylpyrazole (15b)
Colorless oil; yield: 0.86 g (51%); Rf 0.52 (hexane–EtOAc, 10:1).
13C NMR: = 153.12, 146.02, 139.98, 129.22, 128.90, 128.64,
138.83, 134.08, 133.75, 118.85, 113.10, 29.24, 27.37, 16.06, 13.69,
8.68, –4.02.
IR (neat): 1600, 1540, 1500, 1240, 1100 cm–1.
MS (EI): m/z (%)= 582 (M+, 0.5), 525 (12), 489 (8), 391 (31), 292
(17), 277 (68), 135 (29), 41 (100).
1H NMR: = 7.41–7.19 (m, 10 H), 2.42 (s, 3 H), 1.68 (m, 6 H), 1.43
(m, 12 H), 0.87 (t, J = 7.2 Hz, 9 H), 0.19 (s, 6 H).
Anal. Calcd for C30H46N2SiSn: C, 61.96; H, 7.97; N, 4.82. Found:
C, 62.09; H, 7.61; N, 4.62.
13C NMR: = 149.05, 142.50, 142.07, 136.88, 133.58, 129.12,
128.31, 127.61, 126.79, 125.44, 111.48, 27.60, 26.58, 17.28, 13.37,
10.25, –2.40.
MS (EI): m/z = 582 (M+, 1), 525 (18), 447 (12), 335 (5), 291 (17),
214 (33), 156 (35), 57 (100).
4-tert-Butyldiphenylsilyl-5-tributylstannyl-3-methyl-1-
phenylpyrazole (20)
Oil; yield: 0.37 g (21%); Rf 0.28 (hexane–EtOAc, 10:1).
IR (neat): 1650, 1530, 1450, 1390, 1370, 1100 cm–1.
1H NMR: = 7.74 (m, 4 H), 7.43 (m, 11 H), 2.42 (s, 3 H), 1.68 (m,
Anal. Calcd for C30H46N2SiSn: C, 61.96; H, 7.97; N, 4.82. Found:
C, 61.65; H, 8.16; N, 5.11.
6 H), 1.43 (m, 12 H), 1.10 (s, 9 H), 0.85 (t, J = 7.2 Hz, 9 H).
4,5-Bis(dimethylphenylsilyl)-3-methyl-1-phenylpyrazole (16)
Colorless oil; yield: 0.68 g (55%); Rf 0.50 (hexane–EtOAc, 10:1).
IR (neat): 1650, 1500, 1450, 1250, 1100 cm–1.
1H NMR: = 7.52–7.31 (m, 15 H), 2.39 (s, 3 H), 0.41 (s, 6 H), 0.37
(s, 6 H).
13C NMR: = 152.16, 150.09, 139.22, 137.22, 134.65, 131.41,
129.04, 128.97, 127.42, 127.22, 112.19, 29.10, 27.21, 25.26, 19.32,
15.24, 13.39, 8.54.
MS (EI): m/z (%) = 686 (M+, 1), 629 (23), 552 (12), 418 (26), 325
(56), 291 (100), 239 (31), 105 (18), 77 (47), 57 (30).
Anal. Calcd for C38H54N2SiSn: C, 66.57; H, 7.94; N, 4.09. Found:
C, 66.83; H, 8.12; N, 4.36.
13C NMR: = 152.07, 142.78, 142.11, 138.71, 136.65, 133.88,
133.74, 129.33, 128.72, 128.63, 127.82, 127.69, 127.61, 126.95,
112.26, 13.78, –0.90, –3.98.
Acylation of 4-Silyl and 4-Stannyl Azoles; General Procedures
MS (EI): m/z (%) = 426 (M+, 8), 411 (6), 291 (25), 269 (11), 135
(100), 105 (18), 77 (25).
Method A: Benzoyl chloride (562 mg, 4 mmol) and 3,5-dimethyl-
4-dimethylphenylsilyl-1-phenylpyrazole (5b), 4-tributylstannyl-
3,5-dimethyl-1-phenylpyrazole (6b) or 4-tert-butyldiphenylsilyl-
3,5-dimethyl-1-phenylpyrazole (7b) (3 mmol) were refluxed until
TLC indicated complete reaction. The excess of benzoyl chloride
was removed by distillation and the residue was chromatographed
to give 4-benzoyl-3,5-dimethyl-1-phenylpyrazole; mp 100–101 °C
(EtOH) (Lit.13 mp 99–100 °C); yield: 0.43 g (52%); 0.47 g (57%)
and 0.09 g (12%) starting from 5b, 6b and 7b, respectively. When
acetyl chloride or ethyl chloroformate was used the starting materi-
als were recovered.
Anal. Calcd for C26H30N2Si2: C, 73.18; H, 7.09; N, 6.57. Found: C,
73.46; H, 7.41; N, 6.32.
4-tert-Butyldiphenylsilyl-3-methyl-5-dimethylphenylsilyl-1-
phenylpyrazole (17)
Colorless oil; yield: 0.51 g (33%); Rf 0.39 (hexane–EtOAc, 10:1).
IR (CCl4): 1650, 1600, 1550, 1390, 1370, 1250, 1100 cm–1.
1H NMR: = 7.73 (m, 6 H), 7.45–7.30 (m, 14 H), 2.35 (s, 3 H), 1.04
(s, 9 H), 0.37 (s, 6 H).
13C NMR: = 152.17, 142.85, 142.10, 136.19, 135.85, 135.63,
135.38, 133.90, 129.43, 129.34, 128.64, 127.83, 127.56, 126.99,
105.14, 27.86, 18.06, 13.73, –0.91.
MS (EI): m/z (%) = 530 (M+, 0.3), 473 (11), 458 (6), 396 (9), 351
(11), 275 (18), 197 (44), 135 (100), 105 (28), 57 (47).
Method B: A mixture of stannylpyrazole 6b or stannylisoxazole 3
(2 mmol), benzoyl chloride (0.28 g, 2 mmol) and Pd(PPh3)2Cl2 (70
mg, 0.1 mmol) in THF (15 mL) was refluxed until TLC indicated
complete reaction. After addition of aq 0.5 M KF solution, the mix-
ture was extracted with Et2O and the Et2O layer dried (MgSO4). The
residue obtained on evaporation of Et2O was chromatographed to
give the following ketones.
Anal. Calcd for C34H38N2Si2: C, 73.93; H, 7.22; N, 5.28. Found: C,
74.12; H, 7.55; N, 4.93.
4-Benzoyl-3,5-dimethyl-1-phenylpyrazole (21)
Yield: 0.37 g (69%); mp 100–101 °C (EtOH) (Lit.21 mp 99–100 °C).
4,5-Bis(tributylstannyl)-3-methyl-1-phenylpyrazole (18)
Colorless oil; yield: 0.78 g (41%); Rf 0.54 (hexane–EtOAc, 10:1).
IR (neat): 1660, 1610, 1580 cm–1.
4-Benzoyl-3,5-dimethylisoxazole (22)
Yield: 0.18 g (45%); mp 60–61 °C (EtOH) (Lit.22 mp 60–61 °C).
1H NMR: = 7.53–7.34 (m, 5 H), 2.24 (s, 3 H), 1.59 (m, 12 H), 1.31
(m, 18 H), 1.01 (m, 6 H), 0.91 (t, J = 7.1 Hz, 9 H), 0.89 (t, J = 7.3
Hz, 9 H).
13C NMR: = 151.25, 145.01, 139.32, 138.12, 132.94, 129.24,
107.01, 29.03, 27.40, 15.50, 13.66, 11.96.
MS (EI): m/z (%) = 738 (M+, 0.3), 681 (12), 447 (26), 390 (5), 268
(88), 156 (100), 105 (15), 57 (70). Anal. Calcd for C34H62N2Sn2: C,
55.46; H, 8.49; N, 3.80. Found: C, 55.76; H, 8.33; N, 4.07.
4-Cyano-1,3,5-trimethylpyrazole (23)
To a stirred solution of 5a (2 mmol) in CCl4 (2 mL) at 0 °C was add-
ed dropwise chlorosulfonyl isocyanate (2 mmol) in CCl4 (2 mL).
The mixture was then stirred at r.t. until the starting material had
disappeared (TLC). The solvent was removed and the residue was
dissolved in acetone (5 mL) and hydrolyzed by refluxing with 0.1 N
HCl (2 mL) for 5 min. The mixture was extracted with Et2O, dried
(MgSO4), the solvent removed and the residue chromatographed us-
ing CH2Cl2 as eluent to give 0.19 g (72%) of 23; Rf 0.32 (CH2Cl2).
IR (neat): 2230,1550, 1520 cm–1.
1H NMR: = 3.74 (s, 3 H), 2.38 (s, 3 H), 2.33 (s, 3 H).
MS (I): m/z (%) = 135 (M+, 100), 120 (10), 105 (42), 73 (47), 43
(48).
5-Tributylstannyl-3-methyl-4-dimethylphenylsilyl-1-
phenylpyrazole (19)
Colorless oil; yield: 0.87 g (58%); Rf 0.53 (hexane–EtOAc, 10:1).
IR (neat): 1640, 1590, 1530, 1240, 1100 cm–1.
1H NMR: = 7.73–7.29 (m, 10 H), 2.44 (s, 3 H), 1.52 (m, 6 H), 1.37
Anal. Calcd for C7H9N3: C, 62.20; H, 6.71; N, 31.09. Found: C,
62.51; H, 6.98; N, 30,78.
(m, 12 H), 0.93 (t, J = 7.2 Hz, 9 H), 0.38 (s, 6 H).
Synthesis 2001, No. 13, 1949–1958 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis and Reactions of Silylated and Stannylated 1,2-Azoles
1957
Halogenation of 5-Dimethylphenylsilylpyrazoles; General
Procedure
Anal. Calcd for C17H16N2O: C, 77.25; H, 6.10; N, 10.60. Found: C,
76.89; H, 5.87; N, 10.35.
To a solution of 9a (4 mmol) in THF (12 mL) at r.t. was slowly add-
ed Br2 or I2 (4 mmol). The mixture was stirred at r.t. until TLC in-
dicated complete reaction. The mixture was extracted with Et2O,
washed with a sat. aq solution of Na2S2O3 and dried (MgSO4). Re-
moval of the solvent gave the following 4-halo-5-silylpyrazoles.
Oxidation of 3-Methyl-5-dimethylphenylsilyl-1-phenylpyrazole
(9b) to 3-Methyl-1-phenyl-2-pyrazolin-5-one (30)
To a solution of 9b (1 mmol) in anhyd CH2Cl2 (5 mL) under N2 was
added HBF4 Et2O (15 mmol) at r.t in portions of 2.5 mmol during
the reaction time (20 h). The resulting mixture was diluted with
CH2Cl2, washed with a sat. aq solution of NaHCO3 and dried
(MgSO4). Removal of the solvent gave 29; yield: 0.12 g (50%).
4-Bromo-1,3-dimethyl-5-dimethylphenylsilylpyrazole (24)
Colorless oil yield: 1.13 g (92%); Rf 0.38 (hexane–EtOAc, 10:1).
IR (neat): 1645, 1590, 1500, 1250, 1100 cm–1.
1H NMR: = 7.50 (m, 2 H), 7.21 (m, 3 H), 6.52 (s, 1 H), 2.38 (s, 3
H), 0.32(d, J = 7.0 Hz, 6 H).
1H NMR: = 7.52 (m, 2 H), 7.40 (m, 3 H), 3.57 (s, 3 H), 2.24 (s, 3
H), 0.71 (s, 6 H).
MS (EI): m/z (%) = 308 (M+, 75), 293 (100), 229 (79), 213 (26), 199
To a solution of 29 (0.5 mmol) in DMF (10 mL) at –100 °C, under
N2, were added KF (1 mmol) and MCPBA (0.5 mmol). The mixture
was stirred at this temperature until TLC indicated complete reac-
tion. The mixture was diluted with CH2Cl2 and washed with an aq
solution of Na2S2O8, NaHCO3 and NaCl. The organic layer was
dried (MgSO4), the solvent was removed in vacuo and the residue
chromatographed (silica gel/CH2Cl2) to give 30; yield: 0.05 g
(58%); prisms, mp 128–130 °C (H2O) (Lit23 mp 127 °C).
1H NMR: = 7.84 (d, J = 8.0 Hz, 2 H), 7.39 (t, J = 8.0 Hz, 2 H),
7.17 (t, J = 8.0 Hz, 1 H), 3.45 (s, 2 H), 2.18 (s, 3 H).
13C NMR: = 170.52, 139.26, 128.75, 124.00, 118.80, 43.02, 16.92.
(20), 135 (10), 77 (20).
Anal. Calcd for C13H17BrN2Si: C, 50.49; H, 5.54; N, 9.06. Found:
C, 50.63; H, 5.85; N, 8.76.
4-Iodo-1,3-dimethyl-5-dimethylphenylsilylpyrazole (13a)
Colorless oil; yield: 1.35 g (95%).
Under the same conditions the treatment of 24 with another equiv-
alent of Br2 afforded the dibromo product 25.
4,5-Dibromo-1,3-dimethylpyrazole (25)
MS (EI): m/z (%) = 174 (M+, 46), 105 (34), 91 (68), 77 (100), 51
Oil; yield: 0.91 g (96%); Rf 0.33 (hexane–EtOAc, 10:1).
(54).
IR (neat): 1645, 1570, 1430 cm–1.
1H NMR: = 3.81 (s, 3 H), 2.08 (s, 3 H).
MS (EI): m/z (%) = 252 (M+, 50), 237 (13), 173 (46), 158 (10), 132
Acknowledgement
We thank the Ministerio de Ciencia y Tecnología of Spain for sup-
porting this work (Grant BQU2000-0943).
(54), 79 (60).
Anal. Calcd for C5H6Br2N2: C, 23.65; H, 2.38; N, 11.03. Found: C,
23.97; H, 2.53; N, 10.89.
References
Halogenation of 5-Tributylstannylpyrazoles
By the same procedure, starting from the 3-methyl-1-phenyl-5-
tributylstannylpyrazole 10b the corresponding 5-iodopyrazole was
obtained.
(1) See for example: (a) Colvin, E. W. Silicon in Organic
Synthesis; Butterworths: London, 1981. (b) Weber, W. P.
Silicon Reagents for Organic Synthesis; Springer-Verlag:
Berlin, 1983. (c) Patai, S. The Chemistry of Organic Silicon
Compounds; Rappoport, Z., Ed.; Wiley: Chichester, 1989, .
(2) (a) Pereyre, M.; Quintard, J. P.; Rahm, A. Tin in Organic
Synthesis; Butterworths: London, 1987. (b) Yamamoto, Y.
Tetrahedron 1989, 45, 909. (c) Davies, A. G. Organotin
Chemistry; VCH: Weinhein, 1997.
(3) Wakefield, B. J.; Wright, D. J. Adv. Heterocycl. Chem. 1979,
25, 147.
(4) Nesi, R.; Ricci, A.; Taddei, M.; Tedeschi, P.; Seconi, G. J.
Organometal. Chem. 1980, 195, 275.
5-Iodo-3-methyl-1-phenylpyrazole (26)
Yield: 1.02 g (90%); Rf 0.52 (CH2Cl2).
IR (neat): 1630, 1600, 1520 cm–1.
1H NMR: = 7.51– 7.42 (m, 5 H), 6.41 (s, 1 H), 2.33 (s, 3 H).
13C NMR: = 151.79, 140.12, 128.71, 128.23, 126.11, 117.08,
67.87, 13.56.
MS (EI): m/z (%) = 284 (M+, 16), 269 (5), 243 (14), 157 (12),, 127
(5) Hoppe, I.; Schöllkopf, U. Liebigs Ann. Chem. 1979, 219.
(6) Effenberger, F.; Krebs, A. J. Org. Chem. 1984, 49, 4695.
(7) Sakamoto, T.; Shiga, F.; Uchiyama, D.; Kondo, Y.;
Yamanaka, H. Heterocycles 1992, 33, 813.
(15), 116 (26), 77 (50), 41 (100).
Anal. Calcd for C10H9IN2: C, 42.28; H, 3.19; N, 9.86. Found: C,
42.64; H, 2.88; N, 10.11.
(8) Birkofer, L.; Stuhl, O. Top. Curr. Chem. 1980, 88, 62.
(9) (a) Kondo, Y.; Uchiyama, D.; Sakamoto, T.; Yamanaka, H.
Tetrahedron Lett. 1989, 29, 4249. (b) Sakamoto, T.; Kondo,
Y.; Uchiyama, D.; Yamanaka, H. Tetrahedron 1991, 47,
5111.
(10) Mitchell, T. N.; El-Farargy, A.; Moschref, S.-N.;
Gourzoulidou, E. Synlett 2000, 223.
(11) See for example: Cuadrado, P.; González-Nogal, A. M.;
Sánchez, A. J. Org. Chem. 2001, 66, 1961.
(12) (a) Birkofer, L.; Franz, M. Chem. Ber. 1967, 100, 2681.
(b) Birkofer, L.; Franz, M. Chem. Ber. 1971, 104, 3062.
(c) Birkofer, L.; Franz, M. Chem. Ber. 1972, 105, 1759.
(13) Birkofer, L.; Stilke, R. Chem. Ber. 1974, 107, 3717.
(14) Kochetkov, N. K.; Sokolov, S. D. Adv. Heterocycl. Chem.
1963, 2, 382.
3-Methyl-1-phenyl-5-(phenylhydroxymethyl)pyrazole (27)
Starting from 9b (3 mmol) according to the procedure described by
Effenberger6 0.64 g (82%) of 27 was obtained; white crystals; mp
84–86 °C (EtOH–Et2O).
IR (CCl4): 3400, 1600, 1560, 1050 cm–1.
1H NMR: = 7.49–7.36 (m, 5 H), 7.34–7.23 (m, 5 H), 6.03 (s, 1 H),
5.76 (s, 1 H), 2.51 (br s, 1 H), 2.27 (s, 3 H).
13C NMR: = 148.93, 146.04, 141.62,139.47, 128.97, 128.46,
128,38, 127.91, 126.37, 125.46, 106.28, 67.99, 13.43.
MS (EI): m/z (%) = 264 (M+, 98), 247 (5), 204 (10), 187 (13), 159
(57), 105 (25), 77 (100).
Synthesis 2001, No. 13, 1949–1958 ISSN 0039-7881 © Thieme Stuttgart · New York

1958
M. Calle et al.
PAPER
(20) Barbero, A.; Cuadrado, P.; Fleming, I.; González, A. M.;
Pulido, F. J. J. Chem. Soc., Chem. Commun. 1992, 351.
(21) (a) Granberg, I. I.; Kost, A. N. Zh. Obshch. Khim. 1960, 30,
203. (b) Chem. Abstr. 1960, 54, 22583.
(22) (a) Kochetkov, N. K.; Sokolov, S. D.; Zhvirblis, V. E. Zh.
Obshch. Khim. 1960, 30, 3675. (b) Chem. Abstr. 1961, 55,
18707.
(15) Fleming, I.; Henning, R.; Plaut, H. J. Chem. Soc.,Chem.
Commun. 1984, 29.
(16) Auswers, K.; Stuhlmann, A. Chem. Ber. 1926, 59, 1049.
(17) Hüttel, R.; Schäfer, O.; Jochum, P. Liebigs Ann. Chem.
1955, 593, 200.
(18) Fleming, I.; Newton, T. W.; Roessler, F. J. Chem. Soc.,
Perkin Trans. 1 1981, 2527.
(19) Barbero, A.; Cuadrado, P.; Fleming, I.; González, A. M.;
Pulido, F. J.; Sánchez, A. J. Chem. Soc., Perkin Trans. 1
1995, 1525.
(23) Mitra, S. K. J. Ind. Chem. Soc. 1931, 8, 474.
Synthesis 2001, No. 13, 1949–1958 ISSN 0039-7881 © Thieme Stuttgart · New York