Regiospecific synthesis of 5-silyl azoles

Article abstract of DOI:10.1016/S0040-4020(02)00386-1

5-Silylisoxazoles bearing other silyl groups different to the more usual trimethylsilyl have been prepared by condensation of silylalkynones with hydroxylamine hydrochloride. The reaction with hydrazines is more complex and leads to 5-silylpyrazoles or the corresponding hydrazones, which can be cyclized by reaction with electrophiles. This has allowed us to synthesize 5-silylpyrazoles functionalized at C-4 by groups impossible to introduce by electrophilic substitution of the pyrazole nucleus.

Full text of DOI:10.1016/S0040-4020(02)00386-1

TETRAHEDRON
Pergamon
Tetrahedron 58 >2002) 4975±4980
Regiospeci®c synthesis of 5-silyl azoles
p
Puri®cacion Cuadrado, Ana M. Gonzalez-Nogal and Raquel Valero
Â
Â
 Â
Departamento de Quõmica Organica, Universidad de Valladolid, 47011 Valladolid, Spain
Received 7 December 2001; revised 6 March 2002; accepted 4 April 2002
AbstractÐ5-Silylisoxazoles bearing other silyl groups different to the more usual trimethylsilyl have been prepared by condensation of
silylalkynones with hydroxylamine hydrochloride. The reaction with hydrazines is more complex and leads to 5-silylpyrazoles or the
corresponding hydrazones, which can be cyclized by reaction with electrophiles. This has allowed us to synthesize 5-silylpyrazoles
functionalized at C-4 by groups impossible to introduce by electrophilic substitution of the pyrazole nucleus. q 2002 Elsevier Science
Ltd. All rights reserved.
1. Introduction
2. Results and discussion
2.1. Synthesis of 5-silylisoxazoles
Recently,1 we have reported the synthesis of regio-
isomeric silicon and tin 4- or 5-metalated pyrazoles by
silyl or stannylcupration of 4-halopyrazoles or lithiation
with LDA of 5-unsubstituted pyrazoles and the subsequent
treatment with chlorosilanes or chlorostannanes, respec-
tively. Moreover, starting from 5-unsubstituted 4-halopyr-
azoles using both procedures and beginning with 5-
metalation followed by coupling with silyl or stannyl-
cuprates, we have been able to synthesize a variety of
4,5-dimetalated pyrazoles bearing different silyl and
stannyl groups.
We have obtained 5-dimethylphenylsilyl- and 5-tert-butyl-
diphenylsilyl-3-methylisoxazoles according to the proce-
dure described by Birkofer.3 The necessary silylalkynones
have been prepared by us starting from trimethylsilylacetyl-
ene through the following sequence:
The reaction of the disilylacetylene 1b with acetyl chloride
was regiospeci®c and afforded the tert-butyldiphenylsilyl
ketone 2c, in accordance with the results obtained pre-
viously by us4 in the desilylative acetylation of vinylsilanes
bearing two silyl groups >trimethyl and tert-butyldiphenyl)
of very different electrofugacity. However, the acetylation
of 1a gave a mixture of the two possible silylacetylenes 2a
and 2b, the dimethylphenylsilyl derivative 2b being the
major product >Scheme 1).
This methodology can be applied to the preparation of 4-
silyl and 4-stannylisoxazoles, but not to the synthesis of 5-
silyl or 5-stannylisoxazoles, because the 5-lithio intermedi-
ate is opened by ®ssion of N±O and C3±C4 bonds.2
Previously, Birkofer et al.3 synthesized 5-trimethylsilyl
isoxazoles by reaction of trimethylsilylalkynones with hy-
droxylamine hydrochloride. Using this procedure we
have synthesized 5-silylisoxazoles bearing dimethylphenyl
and tert-butyldiphenylsilyl groups. Furthermore, we have
prepared 5-silylpyrazoles starting from differently silylated
acetylenic ketones by condensation with hydrazines. In
some cases, the cyclization step was dif®cult or did not
take place. Fortunately, the hydrazone intermediates were
cyclized in the presence of acids or other electrophiles.
This allowed us to obtain 5-silylpyrazoles functionalized
at C-4 by groups impossible to introduce directly in the
heterocycle.
The reaction of 2b and 2c with hydroxylamine hydro-
chloride led to 5-dimethylphenylsilyl 4b and 5-tert-butyl-
diphenylsilyl-3-methylisoxazole 4c. The cyclization of the
oxime bearing the hindered tert-butyldiphenylsilyl group 3c
was not complete and together with the 5-silylisoxazole 4c
we isolated 3c as a mixture of Z and E isomers >Scheme 2).
2.2. Synthesis of 5-silylpyrazoles
The reaction of silylated acetylenic ketones with hydrazines
is more complicated. The cyclization to the 5-silylpyrazole
or the exclusive formation of the corresponding hydrazone
depends on the nature of the substituents of the hydrazine
and silyl group.
Keywords: 5-silyl azoles; condensation; electrophiles.
Corresponding author. Tel.: 134-983-423213; fax: 134-983-423013;
e-mail: agn@qo.uva.es
p
When free hydrazine or methylhydrazine were used,
only the 4-dimethylphenylsilyl-3-butyn-2-one 2b led to
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020>02)00386-1

4976
P. Cuadrado et al. / Tetrahedron 58 +2002) 4975±4980
Scheme 6.
Scheme 1.
Scheme 7.
3>5)-dimethylphenylsilyl-5>3)-methylpyrazole 7b or the
1,3-dimethyl-5-dimethylphenylsilylpyrazole 8b. On the
contrary, when the silyl group is trimethyl or tert-butyldi-
phenyl substituted the respective hydrazones 5a and 6a or
5c and 6c were isolated >Scheme 3).
Scheme 2.
Nevertheless, when the 4-trimethylsilyl-3-butin-2-one 2a
reacted with an excess of methylhydrazine in the presence
of acetic acid we obtained the 5-trimethylsilylpyrazole 8a
together with a 1.1 mixture of the 1,3-dimethyl and 1,5-
dimethylpyrazole. The latter are the result of the reaction
with methylhydrazine of the desilylated acetylenic ketone
formed in the acid medium necessary for the cyclization.
Better yields of 8a were obtained using methylhydrazine
hydrochloride and sodium acetate >Scheme 4).
The formation of the 5-silyl-1,3-dimethylpyrazoles 8a and
8b can occur by the cyclization from either the hydrazone
intermediates 6a,b resulting from 1,2-addition of methylhy-
drazine by the NH2 group or through the intermediates 9a,b
obtained by 1,4-addition of the NMe group >Scheme 5).
Scheme 3.
The ketone 2c which bears the hindered tert-butyldiphenyl-
silyl group did not cyclize when it was heated with methyl-
hydrazine in the conditions previously cited. In all cases, the
methylhydrazone 6c was exclusively isolated >Scheme 6).
When phenylhydrazine was used as a 1,2-dinucleophile
>free, in the form of hydrochloride or with acid catalysis)
the cyclization did not take place. The reaction with the
three silylated ketones 2a±c afforded only the correspond-
ing phenylhydrazones 10a±c >Scheme 7).
Scheme 4.
Fortunately, the trimethylsilyl and the dimethylphenylsilyl-
hydrazone 10a and 10b could be cyclized to pyrazole
derivatives by reaction with other electrophiles.Thus,
when the phenylhydrazone 10a was treated with acetyl
chloride in methylene chloride at room temperature we
obtained with an excellent yield the 2-acetyl-5-chloro-3-
methyl-5-trimethylsilyl-1-phenyl-3-pyrazoline 11 resulting
from cyclization of the allenic intermediate 12 formed by
1,4-addition >Scheme 8).
The highly functionalized pyrazoline 11 is an interesting
synthon. It contains an allylsilane moiety susceptible of
electrophilic substitution.5,6 Moreover, it bears a chloro a
Scheme 5.

P. Cuadrado et al. / Tetrahedron 58 +2002) 4975±4980
4977
Scheme 10.
5-silyl pyrazoles by condensation of silylalkynones with
hydrazines. Especially interesting is the addition of electro-
philes to the hydrazone intermediates to give in one step
highly functionalized 3-pyrazolines or 5-silylpyrazoles
bearing at C-4 groups which are impossible to introduce
by electrophilic substitution.
Scheme 8.
to the silyl group, and these groups are expected to undergo
a-elimination affording a carbene intermediate whose addi-
tion to ole®ns7 could give heterocyclic spiranes.
3. Experimental
3.1. General
When we used ethyl chloroformate in the same conditions
as described for the acetyl chloride, the starting product 10a
was recovered. Nevertheless, in the presence of aluminum
chloride a 1:3 mixture of the corresponding 5-silylpyrazole
13 and the 4-ethoxycarbonyl-5-silylpyrazole 14 was
obtained >Scheme 9).
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. All reactions involving organometallic reagents were
carried out under N2. The 4-trimethylsilyl-3-butyn-2-one
This result is noteworthy because the 4-ethoxycarbonylation
of the pyrazole nucleus has not been described. In fact, we
recovered untransformed the 3,5-dimethyl-1-phenyl
pyrazole and also the 3-methyl-5-trimethylsilyl-1-phenyl-
pyrazole 13 after re¯uxing with ethyl chloroformate and
aluminum chloride in chloroform for 24 h. Therefore, the
introduction of the ethoxycarbonyl group has to be simul-
taneous with the cyclization >Scheme 10).
1
was purchased from Aldrich. H and 13C NMR spectra
were recorded at 300 and 75 MHz, respectvely in CDCl3
as an internal standard. Carbon multiplicities were assigned
by DEPT experiments. Reactions were monitored by TLC
on a precoated plate of silica gel 60 >nano-SIL-20,
Macheray±Nagel). Flash chromatography was performed
on silica gel 60 >230±240 mesh, M±N).
Other electrophiles, like iodine, were showed to be more
reactive. When the hydrazones 10a,b were stirred at room
temperature with one equivalent of iodine, the 4-iodo-5-
silylpyrazoles 15a,b were isolated >Scheme 11).
3.2. Preparation of silylalkynones 2a±c
To a stirred solution of trimethylsilylacetylene >12mmol) in
dry THF >10 mL) at 2788C under N2, BuLi >12mmol,
7.5 mL of a solution 1.6 M in hexane) was added. Then,
the chlorosilane >12mmol) was added dropwise and the
mixture was allowed to warm to 08C and stirred for 3 h.
Quenching with an aq. NH4Cl solution, workup with
ether, drying of the Et2O layer >MgSO4) and chromato-
graphy of the residue obtained after evaporation of Et2O
gave the following products.
In conclusion, we have prepared isoxazoles bearing at C-5
other silyl groups more stable than the usual trimethylsilyl,
which on occasions proved to be more convenient. For
example, we have recently described the reductive cleavage
of 4- and 5-silyl isoxazoles and their homologues to give
silyl b-enaminones of great interest in the construction of
silylated penta- and hexaheterocycles. On occasions, the
trimethylsilyl derivatives were unstable in the acidic condi-
tions neccessary for cyclization to take place and desilylated
heterocycles were obtained. Nevertheless, b-enaminones
bearing more stable silyl groups such as dimethylphenyl,
diphenylmethyl and tert-butyldiphenyl, yielded pyrazoles,
pyrimidines, 2-pyridones and pyrroles, which retain the
silyl group.8 Moreover, we have prepared for the ®rst time
3.2.1. 1-Dimethylphenylsilyl-2-trimethylsilylacetylene
1a. >97%); Rfˆ0.87 >hexane±AcOEt, 20:1); IR >®lm)
1
2100, 1250, 1100 cm21; H NMR d 7.67 >m, 2H), 7.41
>m, 3H), 0.44 >s, 6H), 0.22 >s, 9H); 13C NMR d 136.87,
133.70, 129.38, 127.85, 115.97, 11.37, 20.08, 20.76; MS
>EI) m/z >%) 232 >M1, 22%), 217 >100), 159 >40), 135 >23),
Scheme 9.
Scheme 11.

4978
P. Cuadrado et al. / Tetrahedron 58 +2002) 4975±4980
73 >60).Anal. Calcd for C13H20Si2: C, 67.17; H, 8.67. Found:
C, 66.83; H, 8.42.
C12H15NOSi: C, 66.31; H, 6.96; N, 6.44. Found: C, 66.73;
H, 7.19; N, 6.31.
3.2.2. 1-tert-Butyldiphenylsilyl-2-trimethylsilylacetylene
1b. >99%); Rfˆ0.85 >hexane±AcOEt, 20:1); IR >®lm)
>m, 6H), 1.14 >s, 9H), 0.32>s, 9H); 13C NMR d 135.56,
133.14, 129.63, 127.75, 119.00, 108.98, 26.98, 18.44,
20.10; MS >EI) m/z >%) 336 >M1, 2%), 279 >100), 73 >2),
57 >14). Anal. Calcd for C21H28Si2: C, 74.93; H, 8.38.
Found: C, 75.15; H, 8.16.
3.3.2. Z and E-4-tert-Butyldiphenylsilyl-3-butyn-2-one
oxime 3c. >93%); Rfˆ0.36 >CH2Cl2); IR >KBr) 3300,
1
2120, 1390, 1100 cm21; H NMR d 7.86 >m, 4H), 7.45
1
2190, 1100 cm21; H NMR of the Z-3c:d 8.47 >s br, 1H),
7.84±7.79 >m, 4H), 7.43 >m, 6H), 2.16 >s, 3H), 1.14 >s, 9H);
1H NMR of the E-3c: d 9.08 >s br, 1H), 7.84±7.79 >m, 4H),
7.43±7.37 >m, 6H), 2.14 >s, 3H), 1.13 >s, 9H). The mixture
of Z/E-3c was cyclized by heating at 1908C/0.1 mm Hg to
give the following.
To a solution of 1a or 1b >11.8 mmol) in CH2Cl2 >10 mL)
cooled at 2208C for 1a and 08C for 1b was added acetyl
chloride >11.8 mmol, 0.83 mL) and freshly sublimed alu-
minum chloride >11.8 mmol, 1.584 g). The reaction was
stirred at this temperature until TLC indicated complete
reaction >2±3 h). The mixture was hydrolyzed with aq.
NH4Cl and the organic layer washed with a sodium hydro-
gen carbonate solution and brine, dried >MgSO4) and
distilled to isolate 2a and 2b or chromatographed to purify
2c.
3.3.3. 3-Methyl-5-tert-butyldiphenylsilylisoxazole 4c.
>41%); mp 96±978C >from hexane) Rfˆ0.43 >CH2Cl2); IR
1
>®lm) 1590, 1550, 1450, 1100 cm21; H NMR d 7.62>m,
4H), 7.35 >m, 6H), 6.20 >s, 1H), 2.32 >s, 3H), 1.17 >s, 9H);
13C NMR d 174.30, 157.59, 136.04, 132.01, 129.92, 127.88,
117.92, 27.48, 18.52, 10.81; MS >EI) m/z >%) 321 >M1, 7%),
264 >100), 223 >45), 57 >8). Anal. Calcd for C20H23NOSi: C,
74.72; H, 7.21; N, 4.36. Found: C, 74.56; H, 7.08; N, 4.50.
3.3.4. 4-Trimethylsilyl-3-butyn-2-one hydrazone 5a.
>84%);Rfˆ0.54 >CH2Cl2); IR >®lm) 3350, 3200, 2140,
1
1250 cm21; H NMR d 7.47 >s, 1H), 6.06 >s, 1H), 2.32 >s,
3.2.3. 4-Trimethylsilyl-3-butin-2-one 2a. >21%); bp
1568C.
3H), 0.27 >s, 9H); 13C NMR d 128.76, 107.27, 88.90, 21.80,
20.32; MS >EI) m/z >%) 154 >M1, 30%), 139 >100), 98 >47),
81 >6), 73 >8). Anal. Calcd for C7H14N2Si: C, 54.49; H, 9.15;
N, 18.16. Found: C, 54.23; H, 8.97, N, 18.29.
3.2.4. 4-Dimethylphenylsilyl-3-butin-2-one 2b. >63%); bp
79±818/0.5 mmHg;; Rfˆ0.40 >hexane±AcOEt,20:1); IR
1
>®lm) 2150, 1670, 1260, 1100 cm21; H NMR d 7.66 >m,
2H), 7.48 >m, 3H), 2.40 >s, 3H), 0.50 >s, 6H); 13C NMR d
184.20, 139.72, 133.64, 129.20, 127.65, 103.44, 95.22,
32.51, 21.69; MS >EI) m/z >%) 202 >M1, 8%), 201 >24),
187 >100), 159 >84), 145 >84), 129 >35),77 >19). Anal. Calcd
for C12H14OSi: C, 71.24; H, 6.97. Found: C, 70.97; H, 7.12.
3.3.5. 4-Trimethylsilyl-3-butyn-2-one methylhydrazone
1
6a. >70%); Rfˆ0.50 >CH2Cl2); H NMR d 3.02>s, 3H),
2.00 >s, 3H), 0.24 >s, 9H); 13C NMR d 128.31, 104.96,
90.71, 38.47, 18.39, 1.33; MS >EI) m/z >%) 168 >M1,
28%), 153 >100), 97 >4), 95 >5), 73 >15), 59 >22). Anal.
Calcd for C8H16N2Si: C, 57.09; H, 9.58; N, 16.64. Found:
C, 56.89; H, 9.26; N, 16.42.
3.2.5. 4-tert-Butyldiphenylsilyl-3-butin-2-one 2c. >70%);
Rfˆ0.42>hexane±AcOEt, 20:1); mp 48 8C >from hexane);
IR >®lm) 2060, 1680, 1100 cm21; 1H NMR d 7.75 >m, 4H),
7.41 >m, 6H), 2.46 >s, 3H), 1.12 >s, 9H); 13C NMR d 183.92,
135.46, 131.34, 130.01, 127.94, 105.72, 92.96, 32.76, 29.00,
26.90; MS >EI) m/z >%) 249 >M12tBu, 36%), 207 >20), 57
>100), 43 >46). Anal. Calcd for C20H22OSi: C, 78.38; H,
7.24. Found: C, 78.65; H, 6.95.
3.3.6. 4-tert-Butyldiphenylsilyl-3-butyn-2-one hydrazone
5c. >79%); Rfˆ0.43 >CH2Cl2); IR >®lm) 3400, 3250, 2110,
1100 cm21; 1H NMR d 7.80 >m, 4H), 7.38 >m, 6H), 6.03 >s,
2H), 2.18 >s, 3H), 1.14 >s, 9H); 13C NMR d 135.50, 132.25,
129.8, 128.49, 127.70, 102.70, 99.22, 27.04, 21.98, 18.40;
MS >EI) m/z >%) 320 >M1, 14%), 263 >100), 222 >51), 185
>15), 77 >3), 57 >8). Anal. Calcd for C20H24N2Si: C, 74.95;
H, 7.55; N, 8.74. Found: C, 75.12; H, 7.33; N, 8.56.
3.3. Reaction of 2a±c with hydroxylamine or hydrazines.
Typical procedure
3.3.7. 4-tert-Butyldiphenylsilyl-3-butyn-2-one methyl-
hydrazone 6c. >59%); Rfˆ0.42>CH Cl2); IR >®lm) 3300,
A mixture of the silylalkynone 2a±c >3 mmol) and hydroxyl-
amine hydrochloride or hydrazine hydrochlorides >6 mmol)
and sodium acetate >9 mmol) or free hydrazines >6 mmol),
was re¯uxed in ethanol >12mL) until TLC indicated
complete reaction. The solvent was evaporated under
reduced pressure and the residue was extracted with
CH2Cl2/H2O. The organic layer was dried >MgSO4) and
concentrated and the residue was chromatographed to give
the following products.
2
1
2150, 1100 cm21; H NMR d 7.80 >m, 4H), 7.46 >m, 6H),
6.06 >s, 1H), 3.05 >d, Jˆ4.8 Hz, 3H), 2.13 >s, 3H), 1.13 >s,
9H); 13C NMR d 135.50, 131.37, 130.03, 127.97, 123.31,
105.73, 93.04, 32.83, 26.94, 22.67, 18.50; MS >EI) m/z >%)
334 >M1, 32%), 277 >52), 236 >35), 183 >9), 95 >8), 77 >18),
57 >100). Anal. Calcd for C21H26N2Si: C, 75.40; H, 7.83; N,
8.37. Found: C, 75.24; H, 7.96; N, 8.12.
3.3.8. 3-Methyl-5-dimethylphenylsilylpyrazole 7b. >54%);
1
Rfˆ0.42>CH Cl2); IR >®lm) 3200, 1260, 1120 cm21; H
3.3.1. 3-Methyl-5-dimethylphenylsilylisoxazole 4b. >73%);
2
1
Rfˆ0.42>CH Cl2); IR >®lm) 1590, 1250, 1100 cm21; H
NMR d 9.63 >s, 1H), 7.61 >m, 2H), 7.39 >m, 3H), 6.10 >s,
1H), 2.36 >s, 3H), 0.34 >s, 6H); 13C NMR d 143.25, 140.13,
133.02, 132.93, 129.14, 127.64, 104.49, 11.95, 0.86. Anal.
Calcd for C12H16N2Si: C, 66.62; H, 7.45; N, 12.95. Found:
C, 66.39; H, 7.62; N, 13.06.
2
NMR d 7.60 >m, 2H), 7.35 >m, 3H), 6.29 >s, 1H), 2.33 >s,
3H), 0.64 >s, 6H); 13C NMR d 176.09, 157.67, 139.94, 129.21,
127.76, 114.66, 10.73, 20.05; MS>EI) m/z >%) 217 >M1, 4%),
202 >30), 174 >46), 161 >48), 135 >100). Anal. Calcd for

P. Cuadrado et al. / Tetrahedron 58 +2002) 4975±4980
4979
3.3.9. 1,3-Dimethyl-5-trimethylsilylpyrazole 8a. >60%);
Rfˆ0.27 >hexane±AcOEt, 10:1); spectroscopic data were
the same as those described by Effenberger.9
1660, 1590, 1250 cm21;1HNMRd 7.37±7.26>m,5H), 5.36>s,
1H), 2.15>s,3H), 1.92>s, 3H), 0.17>s, 9H);13CNMRd 174.73,
149.94, 139.42, 135.00, 129.66, 129.31, 119.88, 95.98, 31.72,
20.73, 22.69; MS >EI) m/z >%) 293 >M12Me, 4%), 265 >6),
231 >18), 216 >94), 215 >10), 200 >10), 174 >7), 105 >6), 93
>100), 73 >72). Anal. Calcd for C15H21ClN2OSi: C, 58.33; H,
6.85; N, 9.07. Found: C, 58.52; H, 6.73; N, 8.91.
3.3.10. 1,3-Dimethyl-5-dimethylphenylsilylpyrazole 8b.
>51%); Rfˆ0.28 >hexane±AcOEt, 10:1); IR >®lm) 1580,
1
1500, 1470, 1270, 1100 cm21; H NMR d 7.73 >m, 2H),
7.39 >m, 3H), 6.21 >s, 1H), 3.68 >s, 3H), 2.29 >s, 3H), 0.58
>s, 6H); 13C NMR d 147.38, 141.22, 136.24, 133.80, 129.54,
127.99, 115.24, 39.23, 12.90, 0.87. MS >EI) m/z >%) 230
>M1, 19%), 215 >38), 135 >46), 95 >5), 77 >100). Anal. Calcd
for C13H18N2Si: C, 67.77; H, 7.88; N, 12.16. Found: C,
67.56; H, 7.59; N, 12.31.
>b) Ethyl chloroformate >2.2 mmol, 0.22 mL) and the
phenylhydrazone 10a >2mmol) were added successively
to freshly sublimed aluminum chloride >2.2 mmol, 0.293 g),
in CH2Cl2 >5 mL) at room temperature. The stirred mixture
was re¯uxed until TLC indicated complete reaction,
neutralised with an ice-cooled 1 M solution of NaHCO3,
and extracted with CH2Cl2. The combined organic layers
were dried >MgSO4), the solvent evaporated and the residue
chromatographed >SiO2, CH2Cl2) to give the following
compounds:
3.3.11. 4-Trimethylsilyl-3-butyn-2-one phenylhydrazone
10a. >80%); Rfˆ0.44 >hexane±CH2Cl2, 10:1); IR >®lm)
1
3320, 2160, 1630, 1250 cm21; H NMR d 8.33 >s, 1H),
7.84 >t, Jˆ7 Hz, 2H), 7.10 >d, Jˆ7 Hz, 2H), 6.92 >t,
Jˆ7 Hz, 1H), 2.18 >s, 3H), 0.35 >s, 9H); 13C NMR d
143.91, 129.23, 123.29, 120.25, 112.84, 107.80, 96.00,
21.65, 20.19; MS >EI) m/z >%) 230 >M1, 46%), 215 >15),
185 >3), 105 >35), 77 >100), 73 >15). Anal. Calcd for
C13H18N2Si: C, 67.77; H, 7.88; N, 12.16. Found: C, 67.92;
H, 7.63; N, 11.98.
3.4.2. 3-Methyl-5-trimethylsilyl-1-phenylpyrazole 13.
>21%), whose spectroscopic data are identical to those
earlier reported by us.8.
3.4.3.
4-Ethoxycarbonyl-3-methyl-5-trimethylsilyl-1-
phenylpyrazole 14. >73%); Rfˆ0.36 >CH2Cl2); IR >®lm)
1
1710, 1250 cm21; H NMR d 7.20±7.33 >m, 5H), 4.24 >q,
3.3.12. 4-Dimethylphenylsilyl-3-butyn-2-one phenyl-
hydrazone 10b. >86%); Rfˆ0.61 >hexane±AcOEt, 20:1);
Jˆ7 Hz, 2H), 2.27 >s, 3H), 1.29 >t, Jˆ8 Hz, 3H), 0.09 >s,
9H); 13C NMR d 167.66, 153.47, 151.41, 141.62, 136.16,
132.31, 130.79, 126.01, 68.01, 24.55, 14.41, 20.08. MS
>EI) m/z >%) 302>M 1, 85%), 258 >5), 229 >50), 225 >10),
105 >22), 97 >30), 77 >100), 73 >50). Anal. Calcd for
C16H22N2O2Si: C, 63.54; H, 7.33; N, 9.26. Found: C,
63.34; H, 7.14; N, 9.38.
1
IR >®lm) 3300, 2110, 1260, 1100 cm21; H NMR d 8.32
>s, 1H), 7.62 >m, 2H), 7.40 >m, 3H), 7.29 >t, Jˆ8 Hz, 2H),
7.00 >d, Jˆ8 Hz, 2H), 6.89 >t, Jˆ8 Hz, 1H), 2.19 >s, 3H),
0.59 >s, 6H); 13C NMR d 143.79, 139.77, 133.60, 129.87,
129.22, 128.17, 123.03, 120.29, 112.82, 106.04, 97.75,
21.56, 21.13; MS >EI) m/z >%) 292 >M1, 25%), 277 >8),
199 >10), 159 >18), 135 >27), 105 >52), 77 >100). Anal. Calcd
for C18H20N2Si: C, 73.92; H, 6.89; N, 9.58. Found: C, 74.08;
H, 7.03; N, 9.34.
>c) To a solution of the phenylhydrazones 10a,b >3 mmol) in
dry THF >10 mL) at room temperature was slowly added
iodine >3 mmol, 0.750 g). The reaction mixture was stirred
at this temperature until the total disappearance of the start-
ing product >TLC). After adding a solution of concentrated
sodium thiosulfate, the mixture was stirred until it became
colourless. The aq. layer was separated and extracted with
ether and the combined organic phases were dried >MgSO4)
and evaporated. The residue was chromatographed to give:
3.3.13. 4-tert-Butyldiphenylsilyl-3-butyn-2-one phenyl-
hydrazone 10c. >97%); Rfˆ0.90 >hexane±AcOEt, 20:1);
1
IR >®lm) 3300, 2110, 1390, 1370, 1100 cm21; H NMR d
8.55 >s, 1H), 7.91 >m, 4H), 7.52>m, 6H), 7.32>t, Jˆ8 Hz,
2H), 7.04 >d, Jˆ8 Hz, 2H), 6.92 >t, Jˆ8 Hz, 1H), 2.32 >s,
3H), 1.36 >s, 9H); 13C NMR d 143.77, 135.47, 132.22,
129.92, 129.25, 127.98, 122.97, 120.36, 112.76, 103.41,
100.11, 27.09, 21.60, 18.5; MS >EI) m/z >%) 396 >M1,
21%), 339 >16), 298 >25), 220 >75), 181 >42), 105 >100),
57 >64). Anal. Calcd for C26H28N2Si: C, 78.74; H, 7.12; N,
7.06. Found: C, 78.47; H, 7.32; N, 6.97.
3.4.4. 4-Iodo-3-methyl-5-trimethylsilyl-1-phenylpyrazole
15a. >79%); Rfˆ0.29 >hexane±AcOEt, 10:1); IR >®lm)
1
1580, 1250 cm21; H NMR d 7.43 >m, 3H), 7.36 >m, 2H),
2.33 >s, 3H), 0.16 >s, 9H); 13C NMR d 151.23, 144.23,
142.96, 128.84, 127.18, 126.20, 57.42, 13.73, 0.08. MS
>EI) m/z >%) 356 >M1, 100%), 341 >75), 229 >5), 214
>24), 127 >5), 105 >7), 77 >5), 73 >15). Anal. Calcd for
C13H17IN2Si: C, 43.83; H, 4.81; N, 7.86. Found: C, 44.01;
H, 4.56; N, 7.62.
3.4. Cyclization of N-phenylhydrazones by reaction with
electrophiles
>a) To a solution of the hydrazone 10a >5 mmol) in dry
CH2Cl2 >20 mL) was added at room temperature acetyl
chloride >7.5 mmol, 0.67 mL). After stirring for 24 h at
this temperature, the mixture was diluted with CH2Cl2,
washed with sodium bicarbonate aq. solution and the
organic layer dried >MgSO4) and evaporated under reduced
pressure. The residue was puri®ed by ¯ash chromatography
>SiO2, CH2Cl2) to give the following.
3.4.5. 4-Iodo-3-methyl-5-dimethylphenylsilyl-1-phenyl-
pyrazole 15b. >84%); colourless crystals; mp 86±888C
>from hexane).1
Acknowledgements
Â
We thank the Ministerio de Ciencia y Tecnologõa of Spain
for supporting this work >Grant BQU2000-0943).
3.4.1. 2-Acetyl-5-chloro-3-methyl-1-phenyl-5-trimethyl-
silyl-3-pyrazoline 11. >81%);Rfˆ0.42>CH Cl2); IR >®lm)
2

4980
P. Cuadrado et al. / Tetrahedron 58 +2002) 4975±4980
5. Chan, T. H.; Fleming, I. Synthesis 1979, 775±778.
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