Synthesis of [2-(Trimethylsilyl)ethynyl]pyrazoles based on bis(trimethylsilyl)acetylene and arylacetyl chlorides

Article abstract of DOI:10.1002/ejoc.201200807

A practical approach to the synthesis of [2-(trimethylsilyl)ethynyl] pyrazoles was developed through condensation of hydrazines with enynones that are easily accessible frombis(trimethylsilyl)acetylene and arylacetyl chlorides. Optimized conditions for reactions with monoarylhydrazines permit the chemoselective formation of 5-alkynylpyrazoles in high yields (48-94 %). When monoalkylhydrazines or the parent hydrazine is used, mixtures of 3- and 5-alkynylpyrazoles are formed in 73-79 % yields. The method uses inexpensive starting materials and can be applied to a variety of substrates, which makes it convenient for the synthesis of alkynylpyrazoles. A three-step method for the synthesis of 5-alkynylpyrazoles through a transformation of bis(trimethylsilyl) acetylene to enynones followed by their condensation with hydrazines is described. The chemoselectivity of the last stage is discussed.

Full text of DOI:10.1002/ejoc.201200807

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FULL PAPER
DOI: 10.1002/ejoc.201200807
Synthesis of [2-(Trimethylsilyl)ethynyl]pyrazoles Based on Bis(trimethylsilyl)-
acetylene and Arylacetyl Chlorides
Alena S. Pankova,[a] Pavel R. Golubev,[a] Ivan V. Ananyev,[b] and Mikhail A. Kuznetsov*[a]
Keywords: Synthetic methods / Nitrogen heterocycles / Chemoselectivity
A practical approach to the synthesis of [2-(trimethylsilyl)-
ethynyl]pyrazoles was developed through condensation of
hydrazines with enynones that are easily accessible from
bis(trimethylsilyl)acetylene and arylacetyl chlorides. Opti-
high yields (48–94%). When monoalkylhydrazines or the
parent hydrazine is used, mixtures of 3- and 5-alkynylpyr-
azoles are formed in 73–79% yields. The method uses inex-
pensive starting materials and can be applied to a variety of
mized conditions for reactions with monoarylhydrazines per- substrates, which makes it convenient for the synthesis of
mit the chemoselective formation of 5-alkynylpyrazoles in
alkynylpyrazoles.
with a (trimethylsilyl)ethynyl group in the side chain are
known.[13,19–21] We decided to employ a trimethylsilyl group
(TMS) on the acetylene because it could be easily removed
by treatment with base in protic solvent,[22,23] or replaced
by a halogen atom,[24,25] which offers diverse synthetic po-
tential including cross-coupling reactions.
Herein we report a new general and straightforward syn-
thesis of hitherto unknown 3- and 5-(trimethylsilyl)ethynyl-
pyrazoles from readily available starting materials. Our
three-step sequence begins with a transformation of bis(tri-
methylsilyl)acetylene (1) to enynones 4 followed by their
condensation with monosubstituted hydrazines.
Introduction
Among the diverse azole scaffolds that have been discov-
ered in various natural compounds,[1] the pyrazole unit is
particularly widespread and is often found in agrochem-
icals, biologically active molecules, dyes, catalysts and com-
plexing agents.[2–8] At the same time aryl- and heteroaryl-
substituted alkynes are used as convenient synthetic precur-
sors for a wide range of target compounds.[9,10] Therefore
alkynyl-substituted pyrazoles are of particular interest act-
ing as a base for construction of more complex heterocyclic
systems. At present there are two frequently used synthetic
approaches to alkynylpyrazoles. The first protocol relies on
diacetylenic ketones, which are not readily available, as key
starting compounds,[11–13] whereas the second involves di-
rect insertion of an acetylenic fragment into a pyrazole ring
by using a Sonogashira coupling.[6,14–19] However, the
aforementioned methods require complex starting com-
pounds that are individual for each reaction and can be
difficult to obtain. Consequently, both methods are de-
scribed in the literature for only a limited range of sub-
strates and cannot be referred to as general.
Results and Discussion
Acetylenic ketones 3a–c are easily accessible by acylation
of bis(trimethylsilyl)acetylene (1) with arylacetyl chlorides
2a–c in good yields (Scheme 1).[26] The activity of the meth-
ylene group of ketones 3a–c in reactions with orthoesters
The overwhelming majority of pyrazoles synthesized by
using these methods possess substituents at the 1-, 3- and
5-positions whereas the terminal carbon atom of the triple
bond is often blocked with a group that renders subsequent
modification of the acetylenic fragment difficult. Only a
handful of pyrazoles unsubstituted in positions 3- or 5- and
[a] Department of Chemistry, Saint-Petersburg State University,
Universitetsky pr. 26, 198504 Saint-Petersburg, Russia
Fax: +007-428-6939
E-mail: mak@mail.wplus.net
Homepage: http://www.chem.spbu.ru/org/537-organics
[b] A.N. Nesmeyanov Institute of Organoelement Compounds,
Russian Academy of Sciences,
Vavilov str. 28, 119991 Moscow, Russia
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200807.
Scheme 1. Synthesis of ketones 4a–c.
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M. A. Kuznetsov et al.
FULL PAPER
appears to be substantially lower than that in 1,3-dicarb-
The reaction of monoarylhydrazines 5a–c (1.5 equiv.)
onyl compounds.[27] That is why, relative to standard pro- with ketones 4a–c (1 equiv.) resulted in preferential or ex-
cedures for ethoxymethylene group insertion,[28,29] our sub- clusive formation of 5-alkynylpyrazoles 6 in 48–94% yields
strates require heating for longer at 130–140 °C to proceed (Table 1). Only in four instances were regioisomeric 3-alk-
to completion, which results in increased tarring and dimin- ynylpyrazoles 7 detected in crude reaction mixtures and
ished yields. Nevertheless, we succeeded in obtaining their amount never exceeded 10%. No other products were
1
ketones 4a–c in 47–68% yields (Scheme 1). In all cases the observed according to the H NMR spectra of the reaction
formation of a single isomer was observed, and no cross mixtures. The yields and ratios for reactions with hydrazines
1
peak between the ortho-aromatic protons and the olefinic were assessed by the H NMR spectra of reaction mixtures
proton was found in its NOESY spectra. However, the lat- with an internal standard, and in all cases the isolated yields
ter argument alone cannot be considered decisive for as- of products were in good agreement with these data. For
signment of the (E)-configuration of a double bond, so we pairs 6d/6g and 7d/7g we isolated both regioisomers and
confirmed the structure of compound 4a by X-ray analysis assigned their structures and substitution patterns unam-
(Figure 1).[30]
biguous by using 1H NOESY NMR spectroscopy (Table 1).
The structures of the other 5-alkynylpyrazoles were then
1
established by analogy using their H and 13C NMR spec-
tral data. In the 13C NMR spectra of 5-alkynylpyrazoles 6
the signal relating to the unsubstituted carbon atom C3 usu-
ally appears around 139 ppm, whereas for 3-alkynylpyr-
azoles 7 the signal for atom C5 is found around 125 ppm.
On the contrary, the signal relating to the heterocyclic pro-
1
ton in the H NMR spectra of 5-alkynylpyrazoles 6 is ob-
served at higher field (≈ 0.1–0.2 ppm) than that for isomeric
3-alkynylpyrazoles 7. The difference in chemical shifts of
carbon atoms of the triple bond in the 13C NMR spectra
could serve as an additional criterion for the assignment of
pyrazoles to 3- or 5-alkynyl substituted compounds. For 5-
alkynylpyrazoles 6 this value is 12–15 ppm, whereas for 3-
alkynylpyrazoles 7 it is less than 3 ppm.
Figure 1. X-ray structure of ketone 4a.
Compounds 4a–c have three electrophilic centers, there-
The exclusive formation of alkynylpyrazoles 6 and 7 sug-
fore formation of diverse heterocycles in reactions with un- gests that in ketones 4a–c the β-atom of the double bond is
symmetrical binucleophiles can be anticipated. For exam- substantially more electrophilic than the β-atom of the tri-
ple, (trimethylsilyl)ethynyl ketones of type 3 in reactions ple bond that leads to the engagement of carbonyl and
with monosubstituted hydrazines give both 3- and 5-(tri- ethoxymethylene groups in the reaction. On the other hand,
methylsilyl)pyrazoles,[31] and in the presence of Na2CO3 in in arylhydrazines 5a–c, the nitrogen atoms differ in their
methanol the corresponding desilylated products can be ob- nucleophilicity as the consequence of the aromatic system’s
tained.[32,33]
conjugation with the unshared electron pair of the substi-
Table 1. Reactions of ketones 4a–c with arylhydrazines 5a–c.
Ketone
Ar1
Hydrazine
Ar2
T [°C]
Pyrazoles 6/7
6:7 (total yield [%])[b]
6 [%][c]
7 [%][c]
4a
4a
4a
4b
4b
4b
4c
4c
4c
4-O2NC6H4
4-O2NC6H4
4-O2NC6H4
Ph
5a[a]
5b
4-MeOC6H4
Ph
4-O2NC6H4
4-MeOC6H4
Ph
4-O2NC6H4
4-MeOC6H4
Ph
20
80
80
20
80
80
20
80
80
a
b
c
d
e
f
g
h
i
1:0 (98)
1:0 (88)
–
10:1 (97)
12:1 (72)
1:0 (62)
9:1 (74)
10:1 (65)
1:0 (66)
94
84
65
80
74
48
61
63
62
–
–
–
6
–
–
3
–
–
[d]
5c
5a[a]
5b
Ph
Ph
5c
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
5a[a]
5b
5c
4-O2NC6H4
[a] Hydrazine 5a was used in its hydrochloride form therefore Et3N was added (see Table 2, Entry 9). [b] According to the 1H NMR
spectra of the reaction mixtures (scale 0.1 mmol, internal standard CH2Br2). [c] Isolated yield. [d] This reaction mixture was not com-
pletely soluble in CDCl3.
2
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Synthesis of (Trimethylsilyl)ethynylpyrazoles
tuted nitrogen atom.[34] Preferential formation of 5-alkynyl- Table 2. Reaction optimization for ketone 4b and hydrazine 5a.
pyrazoles 6a–i originates from the primary attack of the
more nucleophilic terminal hydrazine nitrogen atom at the
more active electrophilic center of unsaturated ketones 4a–c
(EtO–CH=) followed by closure of the five-membered ring.
Small amounts of 3-alkynylpyrazoles, which can be formed
as a result of an initial addition of hydrazine to the carbonyl
group, as well as absence of products resulting from ad-
dition to the triple bond, highlight the sharp decrease of
group reactivity in the sequence EtO–CH= Ͼ C=O ϾϾ
CϵC for compounds 4.
In reactions with nitro ketone 4a or 4-nitrophenylhydra-
zine 5c corresponding 3-alkynylpyrazoles 7 were not de-
tected (Table 1). We ascribe this effect to the strong elec-
tron-withdrawing effect of the nitro group that significantly
decreases the nucleophilicity of the substituted nitrogen
atom in the hydrazine. Meanwhile, in ketone 4a the influ-
ence of the nitro group is transmitted through the conjuga-
tion chain to the carbon atom C1 thus increasing its electro-
philicity and making an attack to the position EtO–CH=
more beneficial which is reflected in the higher chemoselec-
tivity of the reaction.
The character of the substituent in the para-position of
the phenyl ring in hydrazines 5a–c also defines their reactiv-
ity. The conversion of ketones 4a–c with (4-methoxyphen-
yl)hydrazine 5a took 2–3 h at room temperature for comple-
tion (TLC monitoring), whereas their condensation with
phenylhydrazine 5b and (4-nitrophenyl)hydrazine 5c under
the same conditions progressed much slower and, as a con-
sequence, these experiments were carried out at 80 °C.
4(-Methoxyphenyl)hydrazine (5a) was only available as a
hydrochloride salt. In the absence of an auxiliary base, the
reaction selectivity using 5a was quite poor (ca. 2:1). To in-
crease the selectivity we optimized the reaction using ketone
4b and hydrazine 5a as a model and varied the additional
base, ratio of reagents and temperature (Table 2). The best
result was achieved with 1.5 equiv. of triethylamine and hy-
drazine hydrochloride 5a. It appears that in the absence of
a base an equilibrium between the hydrochloride salt and a
free hydrazine is established, and consequently a carbonyl
oxygen atom is protonated by the released acid that in-
creases the electrophilicity of the adjacent carbon atom rel-
ative to the EtO–CH= group, thus leading to a decrease in
the selectivity of the reaction.
4b
5a
T
Total yield
[%][a]
Entry [equiv.]
[equiv.] Base, equiv. [°C] 6d/7d[a]
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1.5
1
1
1
1.5
1
1
1.5
1
1
1
1.5
–
20
20
20
80
1.8:1
2.0:1
5.3:1
6.5:1
7.5:1
5.0:1
3.3:1
8.1:1
10.0:1
52
65
70
66
95
–
AcONa, 1
AcONa, 1
AcONa, 1.5 20
AcONa, 1
K2CO3, 1
Et3N, 1
20
20
20
20
66
41[b]
78
1
Et3N, 1.5
97
[a] According to the 1H NMR spectra of the reaction mixtures
(scale 0.1 mmol, internal standard CH2Br2). [b] In addition the de-
silylated 5-ethynylpyrazole was present in 21% yield.
trends in chemical shifts for carbon atoms C3(5) and triple
bond atoms in 5- and 3-alkynylpyrazoles observed for aryl-
pyrazoles 6 and 7 hold for the 13C NMR spectra of pyr-
azoles 9 and 10. However, contrary to arylpyrazoles, in the
1H NMR spectra of alkylpyrazoles the signal of the hetero-
cyclic proton of 3-alkynylpyrazoles 10 could be found at
higher field than that of 5-alkynylpyrazoles 9.
Table 3. Reactions of ketone 4a with hydrazines 8a–d.
For the most reactive ketone 4a, our method was readily
extended to the synthesis of 1-alkylsubstituted alkynylpyr-
azoles, as well as to the nitrogen-unsubstituted pyrazole.
Treatment of ketone 4a with anhydrous hydrazine 8a gives
a single product, pyrazole 9/10a (Table 3), which exists as
an equilibrium mixture of two tautomeric forms according
1
to its H and 13C NMR spectra. As expected, reactions be-
tween ketone 4a and monoalkylhydrazines 8b–d gave mix-
tures of two regioisomeric pyrazoles 9b–d and 10b–d
(Table 3). All mixtures can be easily separated by column
chromatography on silica gel. The structures of pyrazoles 9
and 10 were assigned based on the 1H, 13C and 2D NOESY
NMR spectroscopic data, and the structure of compound
Hydrazine
R
9 [%]
10 [%]
9/10[a]
8a
8b
8c
8d
H
74
–
nPr
iPr
Bn
28
60
46
45
15
33
1:1.6
4:1
1.4:1
[a] According to the 1H NMR spectra of the reaction mixtures
10b was also confirmed by X-ray analysis (Figure 2).[35] The (scale 0.1 mmol, internal standard CH2Br2).
Eur. J. Org. Chem. 0000, 0–0
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Experimental Section
General Information: Melting points were determined with a Stuart
SMP30 instrument. High-resolution mass spectra were recorded
with a Bruker micrOTOF spectrometer using the electrospray ion-
ization mode. X-ray analysis was performed with a Bruker SMART
APEX II diffractometer. NMR spectroscopic data were recorded
with a Bruker DPX-300 spectrometer (300.13 MHz for 1H and
75.47 MHz for 13C) in CDCl3 and [D6]DMSO and were referenced
to residual proton solvent signals (δH = 7.26 and 2.50 ppm, respec-
tively) and solvent carbon signals (δC = 77.00 and 39.52 ppm,
respectively). The NMR spectroscopic signals of the diarylpyrazole
atoms on the phenyl ring on atom C4 are referred to as “A” and
the atoms on the phenyl ring on atom N1 are referred to as “B”.
The proton systems AAЈXXЈ of the para-substituted and
AAЈXXЈY of the monosubstituted phenyl rings are not seen clearly
in the 1H NMR spectra therefore “apparent” coupling constants
for observed doublets and triplets of appropriate aromatic protons
are given. Ketones 3a,[36] 3b,[26] and 3c[37] were prepared according
to a reported procedure.[26] Column chromatography was per-
formed with Merck silica gel 60.
Figure 2. X-ray structure of pyrazole 10b.
General Procedure for the Preparation of Ketones 4a–c: A mixture
of ketone 3a–c (8.1 mmol), triethyl orthoformate (1.62 mL, 1.45 g,
9.8 mmol) and acetic anhydride (15 mL) was heated to reflux for
16 h. Then the volatile components, with a boiling point under
120 °C, were removed by distillation, and extra portions of triethyl
orthoformate (0.56 mL, 0.50 g, 3.4 mmol) and acetic anhydride
(5 mL) were added. The reaction mixture was heated until TLC
showed no starting ketone remained (8–10 h). Then the mixture
was poured into water and extracted with diethyl ether. The organic
layer was separated, washed with water, saturated aqueous
NaHCO3, brine and dried with Na2SO4. The solvent was removed
under reduced pressure and the residue was purified by flash
chromatography (hexane/EtOAc, 14:1).
The difference in nucleophilicity between the nitrogen
atoms in monoalkylhydrazines is far less pronounced than
that in monoarylsubstituted hydrazines because the donat-
ing alkyl substituent increases the nucleophilicity of the
substituted atom relative to the terminal one. In line with
this, all 3-alkynylpyrazoles were anticipated as a major
product, as was observed in the reaction between ketone 4a
and n-propylhydrazine (8b), in which the ratio of isomers
was approximately 2:1 in favor of 3-alkynylpyrazole 10b
(Table 3). However, the increase of the effective size of the
substituent impedes the approach of the substituted nitro-
gen atom to the fragment EtO–CH= of molecule 4a aiding
the attack on the carbonyl atom that changes chemoselec-
tivity in favor of 5-alkynylpyrazoles. Thus, in reaction with
8b and benzylhydrazine (8d) similar amounts of both pyr-
azoles were found, whereas in the case of the most sterically
demanding isopropylhydrazine (8c) the ratio increased to
4:1 in favor of 5-alkynylpyrazole 9c (Table 3).
(1E)-1-Ethoxy-2-(4-nitrophenyl)-5-(trimethylsilyl)pent-1-en-4-yn-3-
one (4a): Yellow solid, yield 1.74 g (68%); m.p. 81–83 °C. 1H NMR
(300 MHz, CDCl3): δ = 0.27 [s, 9 H, Si(CH3)3], 1.41 (t, J = 7.3 Hz,
3 H, CH3), 4.28 (q, J = 7.3 Hz, 2 H, CH2), 7.50 (d, J = 8.7 Hz, 2
H, Ho), 8.06 (s, 1 H, CH), 8.19 (d, J = 8.7 Hz, 2 H, Hm) ppm. 13C
NMR (75 MHz, CDCl3): δ = –0.7 [Si(CH3)3], 15.3 (CH3), 72.6
(CH2), 97.7, 100.0 (CϵC), 121.2 (C=CH), 122.9 (Cm), 131.1 (Co),
138.1 (Ci), 146.7 (Cp), 166.5 (CHOEt), 175.2 (C=O) ppm. HRMS
(ESI): calcd. for C16H19NO4Si [M + H]+ 318.1156; found 318.1144.
The TMS group could be easily removed by treatment
with bases in protic solvents. It is worth noting that, even
in the presence of hydrazine and monoalkylhydrazines that
are stronger bases than arylhydrazines, the Me3Si–CϵC–
fragment remains intact in during the preparation of all the
pyrazoles.
(1E)-1-Ethoxy-2-phenyl-5-(trimethylsilyl)pent-1-en-4-yn-3-one (4b):
Red oil, yield 1.03 g (47%). 1H NMR (300 MHz, CDCl3): δ = 0.27
[s, 9 H, Si(CH3)3], 1.39 (t, J = 7.3 Hz, 3 H, CH3), 4.21 (q, J =
7.3 Hz, 2 H, CH2), 7.25–7.39 (m, 5 H, Ph), 7.98 (s, 1 H, CH) ppm.
13C NMR (75 MHz, CDCl3): δ = –0.7 [Si(CH3)3], 15.3 (CH3), 71.8
(CH2), 96.6, 100.7 (CϵC), 123.3 (C=CH), 127.4 (Cp), 127.8, 130.1
(Cm,o), 131.0 (Ci), 165.3 (CHOEt), 176.2 (C=O) ppm. HRMS
(ESI): calcd. for C16H20O2Si [M + H]+ 273.1305; found 273.1301.
(1E)-1-Ethoxy-2-(4-methoxyphenyl)-5-(trimethylsilyl)pent-1-en-4-
yn-3-one (4c): Red oil, yield 1.22 g (50%). 1H NMR (300 MHz,
CDCl3): δ = 0.26 [s, 9 H, Si(CH3)3], 1.39 (t, J = 7.3 Hz, 3 H, CH3),
3.80 (s, 3 H, OCH3), 4.21 (q, J = 7.3 Hz, 2 H, CH2), 6.9 (d, J =
8.7 Hz, 2 H, Hm), 7.25 (d, J = 8.7 Hz, 2 H, Ho), 7.95 (s, 1 H,
CH) ppm. 13C NMR (75 MHz, CDCl3): δ = –0.7 [Si(CH3)3], 15.3
(CH3), 55.1 (OCH3), 71.7 (CH2), 96.4, 100.7 (CϵC), 113.3 (Cm),
122.9, 123.1 (Ci, C=CH), 131.2 (Co), 158.8 (Cp), 165.1 (CHOEt),
176.5 (C=O) ppm. HRMS (ESI): calcd. for C17H22O3Si [M + H]+
Conclusions
In summary, we have developed a new general and ef-
ficient practical procedure for the synthesis of previously
unknown
azoles from readily available precursors. Very high chemose-
lectivity is observed when monoarylhydrazines are used.
TMS substituted enynones 4 could be introduced in reac-
1-aryl(alkyl)-5(3)-[(trimethylsilyl)ethynyl]pyr-
tions with various binucleophiles, which could be useful in 303.1411; found 303.1393.
the construction of different heterocycles. Study of these ad-
vantages is the subject of our ongoing investigations.
General Procedure for the Preparation of Pyrazoles: Ketone 4a–c
(1.7 mmol) was dissolved in ethanol (15 mL) in a screw-cap vial.
4
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Synthesis of (Trimethylsilyl)ethynylpyrazoles
The corresponding hydrazine 5a–c or 8a–d (2.5 mmol) was added
to this solution and the mixture was stirred at room temp. (for
hydrazines 5a and 8a–d) or at 80 °C (for hydrazines 5b,c) for 2–4 h
(monitored by TLC). When hydrochloride 5a was used, an equiva-
lent amount of triethylamine (0.35 mL, 0.25 g, 2.5 mmol) was
added to the reaction mixture. When the reaction was finished, the
solvent was removed under reduced pressure and the residue was
purified by column chromatography (CH2Cl2/hexane, 3:1 for pyr-
azoles 6d–h and 7d, g or hexane/EtOAc, 10:1 for pyrazoles 6a,b,i,
9/10a, 9b–d, and 10b–d).
(300 MHz, CDCl3): δ = 0.28 [s, 9 H, Si(CH3)3], 7.35 (t, J = 7.3 Hz,
1 H, HpA), 7.45 (t, J = 7.3 Hz, 2 H, HmA), 7.82 (d, J = 7.3 Hz, 2
H, HoA), 7.99 (s, 1 H, H3), 8.16 (d, J = 8.7 Hz, 2 H, HoB), 8.35 (d,
J = 8.7 Hz, 2 H, HmB) ppm. 13C NMR (75 MHz, CDCl3): δ = –0.7
[Si(CH3)3], 93.6, 108.4 (CϵC), 121.3, 129.1 (C4,5), 122.8, 124.4,
126.8, 128.7 (Co, mA,B), 127.8 (CpA), 130.8 (CiA), 140.1 (C3), 144.5
(CiB), 146.1 (CpB) ppm. HRMS (ESI): calcd. for C20H19N3O2Si [M
+ H]+ 362.1319; found 362.1330.
1,4-Bis(4-methoxyphenyl)-5-(trimethylsilyl)ethynyl-1H-pyrazole
(6g): Yellow solid, yield 391 mg (61%); m.p. 96–98 °C. 1H NMR
(300 MHz, CDCl3): δ = 0.23 [s, 9 H, Si(CH3)3], 3.85 (s, 3 H, OCH3),
3.87 (s, 3 H, OCH3), 6.94–6.99 (m, 4 H, HmA,B), 7.69–7.77 (m, 4
1-(4-Methoxyphenyl)-4-(4-nitrophenyl)-5-(trimethylsilyl)ethynyl-
1H-pyrazole (6a): Yellow solid, yield 625 mg (94%); m.p. 118–
1
120 °C. H NMR (300 MHz, CDCl3): δ = 0.25 [s, 9 H, Si(CH3)3], H, HoA,B), 7.83 (s, 1 H, H3) ppm. 13C NMR (75 MHz, CDCl3): δ
3.88 (s, 3 H, OCH3), 6.99 (d, J = 8.7 Hz, 2 H, HmB), 7.68 (d, J =
= –0.5 [Si(CH3)3], 55.3, 55.5 (2OCH3), 94.5, 105.9 (CϵC), 113.4,
8.7 Hz, 2 H, HoB), 7.96 (s, 1 H, H3), 7.99 (d, J = 8.7 Hz, 2 H, HoA), 114.0 (CmA,B), 120.8, 124.3, 126.8 (CiA, C4,5), 125.0, 127.8 (CoA,B),
8.27 (d, J = 8.7 Hz, 2 H, HmA) ppm. 13C NMR (75 MHz, CDCl3): 133.2 (CiB), 137.7 (C3), 158.8, 158.9 (CpA,B) ppm. HRMS (ESI):
δ = –0.7 [Si(CH3)3], 55.6 (OCH3), 93.4, 107.9 (CϵC), 113.8 (CmB), calcd. for C22H24N2O2Si [M + H]+ 377.1680; found 377.1687.
122.4, 124.4 (C4,5), 124.0 (CmA), 125.1 (CoB), 126.7 (CoA), 132.6
4-(4-Methoxyphenyl)-1-phenyl-5-(trimethylsilyl)ethynyl-1H-pyrazole
(CiB), 138.0 (C3), 138.5 (CiA), 146.4 (CpA), 159.3 (CpB) ppm. HRMS
(6h): Yellow solid, yield 369 mg (63%); m.p. 74–76 °C. 1H NMR
(ESI): calcd. for C21H21N3O3Si [M + H]+ 392.1425; found
(300 MHz, CDCl3): δ = 0.23 [s, 9 H, Si(CH3)3], 3.86 (s, 3 H, OCH3),
392.1388.
6.94–6.99 (m, 2 H, HmA), 7.35–7.40 (m, 1 H, HpB), 7.45–7.50 (m,
4-(4-Nitrophenyl)-1-phenyl-5-(trimethylsilyl)ethynyl-1H-pyrazole
2 H, HmB), 7.75–7.80 (m, 2 H, HoA), 7.81–7.85 (m, 2 H, HoB), 7.87
1
(6b): Yellow solid, yield 523 mg (84%); m.p. 135–137 °C. H NMR
(s, 1 H, H3) ppm. 13C NMR (75 MHz, CDCl3): δ = –0.6 [Si-
(300 MHz, CDCl3): δ = 0.25 [s, 9 H, Si(CH3)3], 7.42–7.52 (m, 3 H, (CH3)3], 55.3 (OCH3), 94.4, 106.2 (CϵC), 114.0 (CmA), 120.7,
H
m,pB), 7.79–7.82 (m, 2 H, HoB), 7.99 (s, 1 H, H3), 7.99–8.02 (m, 2
124.1, 127.3 (CiA, C4,5), 123.4, 127.9, 128.6 (CoA, Co,m,B), 127.5
H, HoA),8.27–8.30 (m, 2 H, HmA) ppm. 13C NMR (75 MHz, (CpB), 138.1 (C3), 139.8 (CiB), 158.9 (CpA) ppm. HRMS (ESI):
CDCl3): δ = –0.7 [Si(CH3)3], 93.4, 108.2 (CϵC), 122.4, 124.8 (C4,5), calcd. for C21H22N2OSi [M + H]+ 347.1574; found 347.1560.
123.7, 124.1 (CmA,B), 126.8 (CoA), 128.2 (CpB), 128.8 (CoB), 138.4
4-(4-Methoxyphenyl)-1-(4-nitrophenyl)-5-(trimethylsilyl)ethynyl-1H-
(CiB), 138.5 (C3), 139.3 (CiA), 146.5 (CpA) ppm. HRMS (ESI):
pyrazole (6i): Yellow solid, yield 414 mg (62%); m.p. 120–122 °C.
calcd. for C20H19N3O2Si [M + H]+ 362.1319; found 362.1295.
1H NMR (300 MHz, CDCl3): δ = 0.28 [s, 9 H, Si(CH3)3], 3.86 (s,
1,4-Bis(4-nitrophenyl)-5-(trimethylsilyl)ethynyl-1H-pyrazole (6c):
Yellow solid, yield 446 mg (65%); m.p. 183–185 °C. The residue
after evaporation of ethanol from the reaction mixture was dis-
solved in EtOAc and the product was precipitated by using hexane.
1H NMR (300 MHz, [D6]DMSO): δ = 0.29 [s, 9 H, Si(CH3)3], 8.14–
8.21 (m, 4 H, HoA,B), 8.35 (d, J = 8.7 Hz, 2 H) and 8.45 (d, J =
3 H, OCH3), 6.97 (d, J = 8.7 Hz, 2 H, HmA), 7.75 (d, J = 8.7 Hz,
2 H, HoA), 7.94 (s, 1 H, H3), 8.15 (d, J = 8.7 Hz, 2 H, HoB), 8.34
(d, J = 8.7 Hz, 2 H, HmB) ppm. 13C NMR (75 MHz, CDCl3): δ =
–0.6 [Si(CH3)3], 55.3 (OCH3), 93.9, 108.1 (CϵC), 114.1 (CmA),
120.6, 123.3 (C4,5), 122.7, 124.4, 128.0 (CoA, Co,mB), 129.0 (CiA),
139.9 (C3), 144.6 (CiB), 146.0 (CpB), 159.3 (CpA) ppm. HRMS
8.7 Hz, 2 H) – (HmA,B), 8.59 (s, 1 H, H3) ppm. 13C NMR (75 MHz, (ESI): calcd. for C21H21N3O3Si [M + H]+ 392.1425; found
[D6]DMSO): δ = 1.8 [Si(CH3)3], 94.2, 109.9 (CϵC), 121.4, 126.0 392.1426.
(C4,5), 124.1, 124.2, 124.9, 127.3 (Co, mA,B), 137.2 (CiA), 140.9 (C3),
1-(4-Methoxyphenyl)-4-phenyl-3-(trimethylsilyl)ethynyl-1H-pyrazole
143.3 (CiB), 146.5, 146.5 (CpA,B) ppm. HRMS (ESI): calcd. for
(7d): Yellow solid, yield 34 mg (6 %); m.p. 94–97 °C. 1H NMR
C20H18N4O4Si [M + Na]+ 429.0989; found 429.1002.
(300 MHz, CDCl3): δ = 0.29 [s, 9 H, Si(CH3)3], 3.83 (s, 3 H, OCH3),
1-(4-Methoxyphenyl)-4-phenyl-5-(trimethylsilyl)ethynyl-1H-pyrazole
(6d): Yellow solid, yield 474 mg (80%); m.p. 90–91 °C. 1H NMR
6.95–6.98 (m, 2 H, HmB), 7.28–7.34 (m, 1 H, HpA), 7.39–7.44 (m,
2 H, HmA), 7.63–7.66 (m, 2 H, HoB), 7.81–7.84 (m, 2 H, HoA), 7.99
(300 MHz, CDCl3): δ = 0.23 [s, 9 H, Si(CH3)3], 3.87 (s, 3 H, OCH3), (s, 1 H, H5) ppm. 13C NMR (75 MHz, CDCl3): δ = –0.4 [Si-
6.96–7.00 (m, 2 H, HmB), 7.28–7.33 (m, 1 H, Hp), 7.39–7.44 (m, 2 (CH3)3], 55.5 (OCH3), 97.5, 99.0 (CϵC), 114.5 (CmB), 120.8 (CmA),
H, HmA), 7.69–7.73 (m, 2 H, HoB), 7.82–7.84 (m, 2 H, HoA), 7.89 124.3 (CoB), 126.5 (C4), 126.7 (C5), 127.1 (CpA), 128.5 (CoA), 131.4,
(s, 1 H, H3) ppm. 13C NMR (75 MHz, CDCl3): δ = –0.6 [Si-
(CH3)3], 55.5 (OCH3), 94.3, 106.2 (CϵC), 113.7 (CmB), 121.3, 126.9
(C4,5), 125.1, 126.6, 128.6 (Co, mA, CoB), 127.1 (CpA), 131.7 (CiA),
133.2 (CiB), 138.0 (C3), 159.0 (CpB) ppm. HRMS (ESI): calcd. for
C21H22N2OSi [M + H]+ 347.1574; found 347.1565.
133.2, 133.3 (CiA,B, C3), 158.6 (CpB) ppm. HRMS (ESI): calcd. for
C21H22N2OSi [M + H]+ 347.1574; found 347.1542.
1,4-Bis(4-methoxyphenyl)-3-(trimethylsilyl)ethynyl-1H-pyrazole
(7g): Yellow solid, yield 21 mg (3%); m.p. 108–110 °C. 1H NMR
(300 MHz, CDCl3): δ = 0.28 [s, 9 H, Si(CH3)3], 3.84 (s, 3 H, OCH3),
3.85 (s, 3 H, OCH3), 6.93–6.98 (m, 4 H, HmA,B), 7.63 (d, J = 8.8 Hz,
2 H, HoA), 7.74 (d, J = 8.4 Hz, 2 H, HoB), 7.92 (s, 1 H, H5) ppm.
13C NMR (75 MHz, CDCl3): δ = –0.3 [Si(CH3)3], 55.3, 55.5
1,4-Diphenyl-5-(trimethylsilyl)ethynyl-1H-pyrazole (6e): Yellow so-
lid, yield 399 mg (74 %); m.p. 63–66 °C. 1H NMR (300 MHz,
CDCl3): δ = 0.23 [s, 9 H, Si(CH3)3], 7.29–7.51 (m, 6 H, Hm,pA,B),
7.84 (m, 4 H, HoA,B), 7.93 (s, 1 H, H3) ppm. 13C NMR (75 MHz, (2OCH3), 97.7, 98.9 (CϵC), 113.9, 114.5 (CmA,B), 120.8 (CoA),
CDCl3): δ = –0.6 [Si(CH3)3], 94.2, 106.5 (CϵC), 121.3, 127.4 (C4,5), 123.8 (C5), 124.0, 126.4, 133.1, 133.3 (CiA,B, C3,4), 128.0 (CoB),
123.6, 126.7, 128.6, 128.6 (Co, mA,B), 127.2, 127.6 (CpA,B), 131.6
(CiA), 138.4 (C3), 139.8 (CiB) ppm. HRMS (ESI): calcd. for
C20H20N2Si [M + H]+ 317.1468; found 317.1480.
158.5, 158.8 (CpA,B) ppm. HRMS (ESI): calcd. for C22H24N2O2Si
[M + H]+ 377.1680; found 377.1677.
4-(4-Nitrophenyl)-3(5)-(trimethylsilyl)ethynyl-1H-pyrazole (9/10a):
Yellowish solid, yield 356 mg (74%); m.p. 184–186 °C. According
to its 1H and 13C NMR spectra at room temp. pyrazole 9/10a exists
1-(4-Nitrophenyl)-4-phenyl-5-(trimethylsilyl)ethynyl-1H-pyrazole
1
(6f): Yellow solid, yield 294 mg (48%); m.p. 154–155 °C. H NMR
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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Job/Unit: O20807
/KAP1
Date: 05-09-12 18:48:35
Pages: 8
M. A. Kuznetsov et al.
FULL PAPER
as a mixture of two tautomeric forms (ratio ≈ 3:1). 1H NMR (300 MHz, CDCl3): δ = 0.29 [s, 9 H, Si(CH3)3], 5.33 (s, 2 H, CH2),
(300 MHz, CDCl3): δ = 0.31 [s, 9 H, Si(CH3)3], 7.94–7.97 (m, 3 H, 7.29–7.41 (m, 5 H, Ph), 7.62 (s, 1 H, H5), 7.90 (d, J = 9.4 Hz, 2 H,
1
Ho, H3), 8.25–8.27 (m, 2 H, Hm), 9.0–12.0 (br. s, 1 H, H1) ppm. H Ho), 8.20 (d, J = 9.4 Hz, 2 H, Hm) ppm. 13C NMR (75 MHz,
NMR (300 MHz, [D6]DMSO): δ = 0.28 [s, 9 H, Si(CH3)3], 8.09 (d,
CDCl3): δ = –0.4 [Si(CH3)3], 56.9 (CH2), 96.9, 99.5 (CϵC), 123.3
J = 8.7 Hz, 2 H, Ho), 8.25 (d, J = 8.7 Hz, 2 H, Hm), 8.07–8.27 (br. (C4), 123.9 (CmA), 126.7 (CoA), 127.8 (C5), 128.0, 129.1 (Co,mB),
s, 0.25 H) and 8.48 (br. s, 0.75 H) – (H3/5), 13.59 (br. s, 0.7 H) and
128.6 (CpB), 132.6 (C3), 135.0 (CiB), 138.5 (CiA), 146.2 (CpA) ppm.
13.87 (br. s, 0.3 H) – (H1) ppm. 13C NMR(75 MHz, CDCl3, 50 °C): HRMS (ESI): calcd. for C21H21N3O2Si [M + H]+ 376.1476; found
δ = –0.4 [Si(CH3)3], 94.1, 103.5 (CϵC), 124.0 (Cm), 126.8 (Co), 376.1458.
133.9 (br. s, C3), 138.4 (Ci), 146.7 (Cp) ppm. Signals of atoms C4
Supporting Information (see footnote on the first page of this arti-
and C5 are not seen owing to strong broadening. HRMS (ESI):
calcd. for C14H15N3O2Si [M + H]+ 286.1006; found 286.0996.
1
cle): Copies of the H and 13C NMR spectroscopic data for com-
pounds 4a–c, 6a–i, 7d, g, 9/10a, 9b–d and 10b–d.
4-(4-Nitrophenyl)-1-propyl-5-(trimethylsilyl)ethynyl-1H-pyrazole
(9b): Yellowish solid, yield 155 mg (28%); m.p. 58–60 °C. 1H NMR
(300 MHz, CDCl3): δ = 0.32 [s, 9 H, Si(CH3)3], 0.95 (t, J = 7.3 Hz,
3 H, CH3), 1.94 (sextet, J = 7.3 Hz, 2 H, CH2), 4.24 (t, J = 7.3 Hz,
2 H, NCH2), 7.80 (s, 1 H, H3), 7.93 (d, J = 8.7 Hz, 2 H, Ho), 8.23
(d, J = 8.7 Hz, 2 H, Hm) ppm. 13C NMR (75 MHz, CDCl3): δ =
–0.5 [Si(CH3)3], 11.1 (CH3), 23.4 (CH2), 52.4 (NCH2), 92.8, 107.7
(CϵC), 122.6, 123.1 (C4,5), 124.0, 126.2 (Cm,o), 136.7 (C3), 138.9
(Ci), 146.1 (Cp) ppm. HRMS (ESI): calcd. for C17H21N3O2Si [M +
H]+ 328.1476; found 328.1486.
Acknowledgments
The authors thank Saint-Petersburg State University for financial
support (research grant number 12.38.16.2011).
[1] A. F. Pozharskii, A. T. Soldatenkov, A. R. Katritzky, Heterocy-
cles in Life and Society, Wiley, Chichester, UK, 1997.
[2] L. Yet, Pyrazoles, in: Comprehensive Heterocyclic Chemistry III
(Eds.: A. R. Katritzky, C. A. Ramsden, E. F. V. Scriven,
R. J. K. Taylor), Elsevier, Oxford, 2008, vol. 4.
[3] L. Yang, F. Okuda, K. Kobayashi, K. Nozaki, Y. Tanabe, Y.
Ishii, M. Haga, Inorg. Chem. 2008, 47, 7154–7165.
[4] S.-Y. Chang, J.-L. Chen, Y. Chi, Y.-M. Cheng, G.-H. Lee, C.-
M. Jiang, P.-T. Chou, Inorg. Chem. 2007, 46, 11202–11212.
[5] E.-M. Chang, C.-T. Lee, C.-Y. Chen, F.-F. Wong, M.-Y. Yeh,
Aust. J. Chem. 2008, 61, 342–349.
1-Isopropyl-4-(4-nitrophenyl)-5-(trimethylsilyl)ethynyl-1H-pyrazole
(9c): Yellowish solid, yield 334 mg (60%); m.p. 94–97 °C. 1H NMR
(300 MHz, CDCl3): δ = 0.32 [s, 9 H, Si(CH3)3], 1.55 (d, J = 6.7 Hz,
6 H, 2CH3), 4.86 (sept, J = 6.7 Hz, 1 H, CH), 7.80 (s, 1 H, H3),
7.93 (d, J = 8.7 Hz, 2 H, Ho), 8.23 (d, J = 8.7 Hz, 2 H, Hm) ppm.
13C NMR (75 MHz, CDCl3): δ = –0.4 [Si(CH3)3], 22.1 (2CH3), 52.3
(CH), 92.7, 107.8 (CϵC), 122.0, 122.7 (C4,5), 124.0, 126.3 (Cm,o),
136.5 (C3), 139.0 (Ci), 146.1 (Cp) ppm. HRMS (ESI): calcd. for
C17H21N3O2Si [M + H]+ 328.1476; found 328.1487.
[6] A. B. Pinkerton, D. Huang, R. V. Cube, J. H. Hutchinson, M.
Struthers, J. M. Ayala, P. P. Vicario, S. R. Patel, T. Wisniewski,
J. A. DeMartino, J.-M. Vernier, Bioorg. Med. Chem. Lett. 2007,
17, 807–813.
[7] O. Rist, M. Begtrup, J. Chem. Soc. Perkin Trans. 1 2001, 1566–
1-Benzyl-4-(4-nitrophenyl)-5-(trimethylsilyl)ethynyl-1H-pyrazole
(9d): Yellowish solid, yield 291 mg (46 %); m.p. 115–117 °C. 1H
NMR (300 MHz, CDCl3): δ = 0.31 [s, 9 H, Si(CH3)3], 5.45 (s, 2 H,
CH2), 7.33–7.35 (m, 5 H, Ph), 7.83 (s, 1 H, H3), 7.92 (d, J = 8.7 Hz,
2 H, Ho), 8.23 (d, J = 8.7 Hz, 2 H, Hm) ppm. 13C NMR (75 MHz,
CDCl3): δ = –0.5 [Si(CH3)3], 54.6 (CH2), 92.8, 108.3 (CϵC), 123.2,
123.2 (C4,5), 124.0 (CmA), 126.3 (CoA), 128.0, 128.7 (Co,mB), 128.2
(CpB), 136.0 (CiB), 137.2 (C3), 138.7 (CiA), 146.3 (CpA) ppm. HRMS
(ESI): calcd. for C21H21N3O2Si [M + H]+ 376.1476; found
376.1445.
1568.
[8] J. A. Cadieux, Z. Zhang, M. Mattice, A. Brownlie-Cutts, J. Fu,
L. G. Ratkay, R. Kwan, J. Thompson, J. Sanghara, J. Zhong,
Y. P. Goldberg, Bioorg. Med. Chem. Lett. 2012, 22, 90–95.
[9] L. Brandsma, Synthesis of Acetylenes, Allenes and Cumulenes:
Methods and Techniques, Elsevier, Oxford, 2004.
[10] F. Diederich, P. Stang, R. R. Tykwinski (Eds.), Acetylene
Chemistry: Chemistry, Biology, and Material Science, Wiley-
VCH, Weinheim, Germany, 2005.
[11] N. P. Bowling, N. J. Burrmann, R. J. Halter, J. A. Hodges, R. J.
McMahon, J. Org. Chem. 2010, 75, 6382–6390.
[12] M. F. A. Adamo, R. M. Adlington, J. E. Baldwin, G. J. Pritch-
ard, R. E. Rathmell, Tetrahedron 2003, 59, 2197–2205.
[13] C. D. Smith, K. Tchabanenko, R. M. Adlington, J. E. Baldwin,
Tetrahedron Lett. 2006, 47, 3209–3212.
[14] O. RЈkyek, N. Halland, A. Lindenschmidt, J. Alonso, P. Linde-
mann, M. Urmann, M. Nazar, Chem. Eur. J. 2010, 16, 9986–
9989.
[15] M. I. Rodriguez-Franco, I. Dorronsoro, A. Martinez, Synthesis
2001, 1711–1715.
[16] G. Vilkauskaitae, W. Holzer, A. Sackus, Eur. J. Org. Chem.
2011, 5123–5133.
4-(4-Nitrophenyl)-1-propyl-3-(trimethylsilyl)ethynyl-1H-pyrazole
(10b): Yellow solid, yield 250 mg (45%); m.p. 102–104 °C. 1H NMR
(300 MHz, CDCl3): δ = 0.28 [s, 9 H, Si(CH3)3], 0.94 (t, J = 7.3 Hz,
3 H, CH3), 1.94 (sextet, J = 7.3 Hz, 2 H, CH2), 4.10 (t, J = 7.3 Hz,
2 H, NCH2), 7.68 (s, 1 H, H5), 7.93 (d, J = 8.7 Hz, 2 H, Ho), 8.22
(d, J = 8.7 Hz, 2 H, Hm) ppm. 13C NMR (75 MHz, CDCl3): δ =
–0.4 [Si(CH3)3], 11.1 (CH3), 23.5 (CH2), 54.7 (NCH2), 97.0, 99.2
(CϵC), 122.5 (C4), 123.9 (Cm), 126.6 (Co), 127.8 (C5), 132.3 (C3),
138.7 (Ci), 146.2 (Cp) ppm. HRMS (ESI): calcd. for C17H21N3O2Si
[M + H]+ 328.1476; found 328.1487.
[17] E. Arbaciauskiene, G. Vilkauskaite, A. Sackus, W. Holzer, Eur.
J. Org. Chem. 2011, 1880–1890.
1-Isopropyl-4-(4-nitrophenyl)-3-(trimethylsilyl)ethynyl-1H-pyrazole
(10c): Yellow solid, yield 84 mg (15%); m.p. 105–108 °C. H NMR
1
[18] X.-J. Wang, J. Tan, K. Grozinger, Tetrahedron Lett. 2000, 41,
(300 MHz, CDCl3): δ = 0.28 [s, 9 H, Si(CH3)3], 1.56 (d, J = 6.7 Hz,
6 H, 2CH3), 4.53 (sept, J = 6.7 Hz, 1 H, CH), 7.72 (s, 1 H, H5),
7.94 (d, J = 8.9 Hz, 2 H, Ho), 8.23 (d, J = 8.9 Hz, 2 H, Hm) ppm.
13C NMR (75 MHz, CDCl3): δ = –0.4 [Si(CH3)3], 22.8 (2CH3), 55.0
(CH), 97.2, 99.1 (CϵC), 122.3 (C4), 123.9 (Cm), 125.4 (Co), 126.6
(C5), 131.9 (C3), 138.8 (Ci), 146.1 (Cp) ppm. HRMS (ESI): calcd.
for C17H21N3O2Si [M + H]+ 328.1476; found 328.1465.
4713–4716.
[19] H. Ichikawa, H. Ohfune, Y. Usami, Heterocycles 2010, 81,
1651–1659.
[20] G. Zoppellaro, M. Baumgarten, Eur. J. Org. Chem. 2005, 2888–
2892.
[21] T. Okitsu, K. Sato, A. Wada, Org. Lett. 2010, 12, 3506–3509.
[22] P. Wautelet, J. Le Moigne, V. Videva, P. Turek, J. Org. Chem.
2003, 68, 8025–8036.
[23] J. Cao, X. Yang, X. Hua, Y. Deng, G. Lai, Org. Lett. 2011, 13,
478–481.
1-Benzyl-4-(4-nitrophenyl)-3-(trimethylsilyl)ethynyl-1H-pyrazole
(10d): Yellow solid, yield 209 mg (33%); m.p. 173–174 °C. 1H NMR
6
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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/KAP1
Date: 05-09-12 18:48:35
Pages: 8
Synthesis of (Trimethylsilyl)ethynylpyrazoles
[24]
[25]
[26]
[31] P. Cuadrado, A. M. Gonzalez-Nogal, R. Valero, Tetrahedron
2002, 58, 4975–4980.
[32] L. de Luca, M. Falorni, G. Giacomelli, A. Porcheddu, Tetrahe-
dron Lett. 1999, 40, 8701–8704.
[33] M. Falorni, G. Giacomelli, A. M. Spanedda, Tetrahedron:
Asymmetry 1998, 9, 3039–3046.
[34] B. V. Ioffe, M. A. Kuznetsov, A. A. Potekhin (Eds.), Chemistry
of Organic Hydrazine Derivatives, “Khimiya”, Leningrad, 1979.
[35] CCDC-885772 contains the supplementary crystallographic
data for 10b. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
A. S. Dudnik, A. W. Sromek, M. Rubina, J. T. Kim, A. V. Ke-
lЈin, V. Gevorgyan, J. Am. Chem. Soc. 2008, 130, 1440–1452.
M. H. Vilhelmsen, A. S. Andersson, M. B. Nielsen, Synthesis
2009, 1469–1472.
F. Lopez, L. Castedo, J. L. Mascarenas, Org. Lett. 2005, 7, 287–
290.
[27] V. V. Mezherizkiy, E. P. Olechnovich, S. M. Luk’janov, G. N.
Dorofeenko, Orthoesters in Organic Synthesis, Publishing house
of Rostov University, Rostov-on-Don, 1976.
[28] L. Crombie, D. E. Games, A. W. G. James, J. Chem. Soc. Perkin
Trans. 1 1979, 464–471.
[29] A. Riahi, M. Shkoor, O. Fatunsin, R. A. Khera, C. Fischer, P.
Langer, Org. Biomol. Chem. 2009, 7, 4248–4251.
[30] CCDC-885771 contains the supplementary crystallographic
data for 4a. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[36] C. Menendez, S. Gau, S. Ladeira, C. Lherbet, M. Baltas, Eur.
J. Org. Chem. 2012, 409–416.
[37] F. T. Boyle, O. Hares, Z. S. Matusiak, W. Li, J. Chem. Soc. Per-
kin Trans. 1 1997, 2707–2712.
Received: June 16, 2012
Published Online: ᭿
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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Date: 05-09-12 18:48:35
Pages: 8
M. A. Kuznetsov et al.
FULL PAPER
Heterocyclic Chemistry
A three-step method for the synthesis of 5-
alkynylpyrazoles through a transformation
of bis(trimethylsilyl)acetylene to enynones
followed by their condensation with
hydrazines is described. The chemoselecti-
vity of the last stage is discussed.
A. S. Pankova, P. R. Golubev,
I. V. Ananyev, M. A. Kuznetsov* ....... 1–8
Synthesis of [2-(Trimethylsilyl)ethynyl]-
pyrazoles Based on Bis(trimethylsilyl)-
acetylene and Arylacetyl Chlorides
Keywords: Synthetic methods / Nitrogen
heterocycles / Chemoselectivity
8
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