A convenient synthesis of alkynylpyrazoles

Article abstract of DOI:10.1039/a605542g

Diazomethane add to the enyne sulfones 1,3,4,6-11 regio- and stereo-selectively to give the 4-alkynyl-5-phenylsulfonyl-4,5-dihydro-3H-pyrazoles 12-15 and 17-19, which are converted by MeLi into the 4-alkynyl-1H-pyrazoles 24, 25, 16, 26, 28, 30 in good yields. 4,5-Bis(alkynyl)-1H-pyrazoles 34, 37 are also obtained by the same procedure.

Full text of DOI:10.1039/a605542g

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A convenient synthesis of alkynylpyrazoles
Mitsuhiro Yoshimatsu,*,a Masataka Kawahigashi,b Eiji Hondab and
Tadashi Kataoka b
a
Department of Chemistry, Faculty of Education, Gifu University, Yanagido,
Gifu 501-11, Japan
b Gifu Pharmaceutical University, 6-1, Mitahora-higashi 5-chome, Gifu 502, Japan
D iazomethane add to the enyne sulfones 1, 3, 4, 6–11 regio- and stereo-selectively to give the 4-alkynyl-5-
phenylsulfonyl-4,5-dihydro-3H -pyrazoles 12–15 and 17–19, which are converted by M eLi into the
4-alkynyl-1H -pyrazoles 24, 25, 16, 26, 28, 30 in good yields. 4,5-Bis(alkynyl)-1H -pyrazoles 34, 37 are
also obtained by the same procedure.
Whilst pyrazoles have been widely used as insecticides and
Me
1
2
2
herbicides,1 much attention has been paid to alkynylpyrazoles
H
H
which show cholesterol synthesis-inhibiting activity.2 Several
syntheses of these compounds have been reported. Thus, addi-
tion of diazoalkanes to conjugate enyne compounds affords
a mixture of alkynyl- and alkenyl-pyrazoles,3 whilst the reac-
tions of trimethylsilyl- (TMS)-substituted aryl diynones and
hydrazine give TMS-ethynylpyrazoles in good yields; this
method is applicable only to aryl-substituted derivatives.4
Decarboxylation of the pyrazolopropiolic acids resulted in low
yields of such products.5
SO2H
SO2H
1
2A
4A
LUMO
C1 = 0.62568 a.u.
C2 = –0.57799 a.u.
C1 = 0.63000 a.u.
C2 = –0.55888 a.u.
Fig. 1
N
But
But
i
N
SO2Ph
12
H
H
N
SO2Ph
SO2Ph
H
CH2N2
R
R
H
H
N
SO2Ph
22 (87)
PhO2S
N
N
i
Bu
Bu
N
Base
Me
R
Me
NH
SO2Ph
H
23 (90)
14
Scheme 1
Scheme 2 Reagent: i, hν
Recently, we reported the syntheses and the dehydro-
sulfonylation of conjugate enyne sulfones by MeLi.6 If the
cycloadditions of diazomethane and conjugate enyne sulfones
proceed regioselectively to give 5-sulfonyl-substituted 4-alkynyl-
4,5-dihydro-3H-pyrazoles, we thought that dehydrosulfonyl-
ation of these would give alkynyl pyrazoles (Scheme 1). We now
report such a convenient synthesis of 4-alkynyl-1H-pyrazoles.
Cycloaddition of diazomethane to a conjugate enyne sulfone
1 afforded the pyrazoline† 12 regio- and stereo-selectively. The
enyne sulfone 2 gave a complex mixture. The cycloaddition of
diazomethane and (E)-2-methyl-substituted enyne derivative 4
proceeded in a different orientation to give 5-(hex-1-ynyl)-5-
methyl-4-phenylsulfonyl-3H-pyrazoline 14 in good yield. The
stereochemistry of the pyrazoline 14 was also determined by a
DNOE experiment after cyclopropanation of the compound.
Irradiation of the methyl group on the cyclopropane ring
increased the intensity of the ortho-protons of the PhSO2
group not the intensity of the α-hydrogen to the sulfonyl group.
This orientation of the addition of diazomethane was con-
firmed from the coupling pattern of 1H NMR spectral data,
which exhibited a broad triplet δ 3.71 (J 8 Hz) due to the α-
hydrogen to the sulfonyl group and two doublets δ 4.77 (J 8 and
18 Hz) and δ 4.88 (J 8 and 18 Hz) due to the 3-methylene
protons. The different orientations were difficult to under-
stand. Molecular orbital calculations for compounds 2A and
4A by the PM3 method were performed (see Fig. 1) with
MOPAC Ver. 6.01. The value of the LUMO orbitals of 4A and
2A were almost the same. However, the steric hindrance or
the conformation of compound 4 would strongly affect the
orientation of the addition. On the other hand, the Z-isomer
5 gave a complex mixture; α-phenethyl derivative 15 was
obtained, accompanied by the dehydrosulfonylated product 16
(entry 6). The 1,1-bis(phenylsulfonyl) enynes 7–9 afforded the
adducts 17–19, respectively (entries 7–9). The α-halogen enyne
sulfones 10 and 11 gave the N-methylpyrazoles 20 and 21 but
1
structure of 12 was assigned on the basis of IR and H and 13C
NMR spectral results and an elemental analysis. The IR spec-
trum showed the acetylene absorption at 2225 cmϪ1 and those
for the sulfonyl group at 1300 and 1150 cmϪ1. The olefinic pro-
tons of the enyne sulfone 1 at δ 6.59, 6.78 disappeared in the 1H
NMR spectrum and new proton resonances due to the pyrazo-
line at δ 3.50–3.58 (5-H), 4.98–5.02 (3-H) and 5.41 (dt, J 7 and 2
Hz, 4-H) were observed. The 13C NMR results and the elem-
ental analysis were satisfied by structure 12. The stereo-
chemistry of the product 12 was determined after the cyclopro-
panation of the compound. Upon photoirradiation, denitro-
genation of 12 proceeded easily7 to give the cyclopropane 22
as a single trans-isomer with the repeated trans-coupling con-
stant at J 4 Hz (Scheme 2). The Ph-substituted enyne sulfone 3
gave 1H-pyrazoline 13; however, the butyl-substituted
† For convenience, the name pyrazoline is used to refer to the 4,5-
dihydro-3H-pyrazole system.
J. Chem. Soc., Perkin Trans. 1, 1997
695

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Table 1 Cycloadditions of enyne sulfones with CH2N2
Entry
Enyne sulfone
Products (% yield)
But
N
But
12 (87)
1
SO2Ph
SO2Ph
N
H
1
SO2Ph
H
Bu
—
2
3
2
3
NH
Ph
Ph
Bu
Bu
13 (84)
N
H
SO2Ph
SO2Ph
N
N
Me
Bu
14 (79)
4
5
Me
SO2Ph
SO2Ph
H
4
Me
5
—
PhSO2
N
N
But
But
But
15 (46)
16 (17)
6
NH
N
H
SO2Ph
Ph
SO2Ph
6
Ph
Ph
N
N
But
But
Bu
17 (59)
18 (52)
SO2Ph
7
8
PhSO2
PhSO2 SO2Ph
7
N
N
Bu
Ph
SO2Ph
PhSO2
PhSO2
Cl
8
PhSO2 SO2Ph
N
N
Ph
19 (86)
20 (21)
9
SO2Ph
9
PhSO2 SO2Ph
Me
N
N
But
But
N
But
21 (16)
10
SO2Ph
N
Me
10
PhSO2
PhSO2
But
11
SO2Ph
20 (34)
21 (17)
11
Br
not the pyrazolines (entries 10 and 11). The positions of the N-
methyl group were determined by the DNOE enhancement
between the N-Me and the ortho protons of the sulfonyl group.
Irradiation of the N-Me group of 20 increased the intensity of
the ortho protons of the sulfonyl group; however, that of 21 did
not show DNOE enhancement. The regioselectivity for the
cycloadditions of diazomethane is accounted for by the Fron-
tier MO theory that attachment of the sulfonyl group lowers
the energy of the LUMO and thereby enhances the addition at
the vinyl part of the enyne sulfones.8
Next, we examined the dehydrosulfonylations of the pyrazo-
lines by MeLi (see Table 2). The pyrazoline 12 underwent β-
elimination by MeLi to give the 4-alkynyl-1H-pyrazole 24
(80%), the spectral data and the elemental analysis for which
satisfied the assigned structure. Substituted enyne sulfone 13
gave the 4-alkynylpyrazole 25 quantitatively. The enyne 14,
which has no prop-2-ynylic hydrogen at the β-position of the
sulfonyl group, failed to undergo dehydrosulfonylation. The
α-phenethyl derivative 15 afforded the 4-alkynyl-5-phenethyl-
pyrazole 16 in good yield. The 5,5-bis(sulfonyl)pyrazole 17 gave
696
J. Chem. Soc., Perkin Trans. 1, 1997

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Table 2 Reaction of pyrazolines with MeLi
Entry
Alkynylpyrazoline
Products (% yields)
N
N
But
Ph
But
Ph
24 (80)
1
NH
N
H
SO2Ph
H
12
N
NH
N
25 (99)
2
NH
SO2Ph
13
N
N
—
Bu
3
4
Me
SO2Ph
H
14
N
N
N
But
But
NH
16 (66)
H
SO2Ph
Ph
Ph
15
N
N
N
But
But
Bu
Ph
But
Bu
NH
26 (84)
5
SO2Ph
SO2Ph
27 (trace)
29 (trace)
17
18
PhSO2
PhSO2
SO2Ph
PhSO2
PhSO2
PhO2S
PhO2S
PhO2S
N
N
N
Bu
Ph
NH
6
7
28 (95)
SO2Ph
N
N
N
Ph
NH
SO2Ph
PhSO2
30 (88)
31 (6)
19
SO2Ph
PhSO2
the 4-alkynyl-5-phenylsulfonylpyrazole 26, accompanied by a
trace of the alkynylcyclopropane 27 (entry 5). The cyclo-
propane derivatives were found to be easily obtained because of
the denitrogenation of the pyrazolines under room light
(Scheme 3). Thus, the pyrazolines 17 and 18 were stirred in
But
Bu
SO2Ph
SO2Ph
Ph
Ph
32
35
i
i
But
i
17
+ 17
N
N
But
Bu
SO2Ph
SO2Ph
PhSO2
N
N
H
H
27 (40%)
(44%)
SO2Ph
SO2Ph
Bu
i
33 (66%)
Ph
Ph
36 (77%)
18
+ 18
PhSO2
+
ii
29 (56%)
(26%)
N
N
But
Scheme 3 Reagent: i, room light, CHCl3
Bu
NH
NH
CHCl3 for 12 h at room temperature to afford the cyclopropane
derivatives 27 and 29, respectively. The purified 4-(hex-1-
ynyl)pyrazoline 18 also gave the pyrazole 28 in high yield. 4-(2-
Phenylethynyl)pyrazole 19 gave the pyrazole 30, accompanied
by a trace of the cyclopropane 31 (entry 8). We also performed
the desulfonylation of the pyrazolines with other bases such as
LDA, NaH, ButOK, Bu4NF; however, the yields of the pyra-
zoles were rather low by comparison with MeLi.
The reactions of (Z)-enediyne sulfones 32 and 35 with diazo-
methane gave the bis(alkynyl)-substituted 3H-pyrazoles 33 and
36, accompanied by the 1H-bis(alkynyl)pyrazole 34 (Scheme
4). The dehydrosulfonylation of 36 gave the 4,5-bis(alkynyl)-
pyrazole 37.
34 (26%)
37 (90%)
Ph
Ph
Scheme 4 Reagents: i, CH2N2; ii, MeLi–THF
apparatus and are uncorrected. IR spectra of solids (KBr) and
liquids (film) were recorded on a JASCO IRA-100 spectro-
photometer. H NMR spectra were obtained for solution in
1
CDCl3 on a JEOL GX-270 (270 MHz) or a Varian Gemini 2000
(200 MHz) spectrometer with tetramethylsilane as an internal
standard, unless otherwise indicated. 13C NMR spectra and
NOE measurements were run on a JEOL EX-270 spec-
trometer. J Values are given in Hz. Mass spectra were obtained
using a JEOL JMS-D 300 spectrometer with a direct-insertion
probe at 70 eV. All exact mass determinations were obtained on
a JMA 2000 on-line system. Molecular orbital calculations
Experimental
Mps were determined on a Yanagimoto micro-melting point
J. Chem. Soc., Perkin Trans. 1, 1997
697

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were carried out using MOPAC Ver. 6, J. J. Stewart, QCPE Bull.
9, 10 (1989); revised as Ver. 6.01 by Tsuneo Hirano, University
of Tokyo, for HITAC and UNIX machines, JCPE Newsletter,
1, 10 (1989). All enyne sulfones were prepared according to our
previous report.9 Ether refers to diethyl ether.
and 141.2 (s); m/z 252 (M+, base) (Found: C, 80.71; H, 7.90; N,
11.04. C17H20N2 requires C, 80.91; H, 7.99; N, 11.10%).
5,5-Bis(phenylsulfonyl)-4-(3,3-dimethylbut-1-ynyl)-4,5-
dihydro-3H-pyrazole 17. Colourless needles (from CHCl3–
Et2O), mp 97–98 ЊC (decomp.); νmax/cmϪ1 2260 (acetylene) and
1350 and 1150 (SO2); δH (270 MHz, CDCl3) 1.05 (9 H, s,
CH3 × 3), 3.69 (1 H, t, J 9, 4-H), 4.67 (1 H, dd, J 9 and 18, 3-H),
5.24 (1 H, dd, J 9 and 18, 3-H), 7.51–7.61 (4 H, m, ArH), 7.67–
7.75 (2 H, m, ArH), 7.92–7.95 (2 H, m, ArH) and 8.04–8.07 (2
H, m, ArH); δC(67.5 MHz, CDCl3) 27.3 (s), 30.4 (q × 3), 31.5
(d), 65.8 (s), 67.8 (s), 84.6 (t), 95.5 (s), 128.5 (d × 2), 128.9
(d × 2), 131.4 (d × 2), 131.6 (d × 2), 134.9 (d), 135.1 (d), 135.6
(s) and 137.0 (s); m/z 430 (M+) and 125 (base) (Found: C, 58.52;
H, 5.47; N, 6.20. C21H22N2O4S2 requires C, 58.59; H, 5.15; N,
6.51%).
Reactions of the enyne sulfones 1–11 with diazomethane
Typical procedure. An ether (10 cm3) solution of diazo-
methane [generated from N-methylnitrosourea10 (2.0 g, 0.02
mol) and 50% aq. NaOH] was added dropwise to an ether (2
cm3) solution of 5,5-dimethyl-1-phenylsulfonylhex-1-en-3-yne 1
(0.25 g, 1.0 mmol) at 0 ЊC. The resulting precipitate was fil-
tered off and washed with a small amount of ether. The almost
pure (4S*,5R*)-4-(3,3-dimethylbut-1-ynyl)-5-phenylsulfonyl-
4,5-dihydro-3H-pyrazole 12 (0.25 g, 87%) was obtained as col-
ourless needles after recrystallization from CHCl3–Et2O; mp
124–126 ЊC (decomp.); νmax/cmϪ1 2225 (acetylene) and 1300 and
1150 (SO2); δH (270 MHz, CDCl3) 1.04 (9 H, s, CH3 × 3), 3.50–
3.58 (1 H, m, 5-H), 4.98–5.02 (2 H, m, 3-H), 5.41 (1 H, dt, J 7
and 2, 4-H), 7.60–7.65 (2 H, m, ArH), 7.70–7.76 (1 H, m, ArH)
and 7.90–7.94 (2 H, m, ArH); δC(67.5 MHz, CDCl3) 27.3 (s),
30.5 (q × 3), 64.3 (d), 71.2 (s), 76.6 (t), 80.8 (d), 97.9 (s), 128.4
(d × 2), 129.7 (d × 2), 134.5 (d) and 138.1 (s); m/z 290 (M+) and
93 (base) (Found: C, 61.94; H, 6.25; N, 9.68. C15H18N2O2S
requires C, 62.04; H, 6.25; N, 9.65%).
5,5-Bis(phenylsulfonyl)-4-(hex-1-ynyl)-4,5-dihydro-3H-
pyrazole 18. Yellow powder (from CHCl3–Et2O), mp 96–97 ЊC
(decomp.); νmax/cmϪ1 2250 (acetylene) and 1330 and 1150 (SO2);
δH (270 MHz, CDCl3) 0.86 (3 H, t, J 7, CH3), 1.24–1.43 (4 H, m,
CH2CH2), 2.08 (2 H, dt, J 2 and 7, 3Ј-H), 3.75 (1 H, tt, J 2 and
9, 4-H), 4.65 (1 H, dd, J 9 and 18, 3-H), 5.21 (1 H, dd, J 9 and
18, 3-H), 7.48–7.54 (4 H, m, ArH), 7.64–7.70 (2 H, m, ArH),
7.87–7.91 (2 H, m, ArH) and 7.99–8.03 (2 H, m, ArH); δC(67.5
MHz, CDCl3) 13.5 (q), 18.4 (t), 21.7 (t), 30.2 (t), 31.1 (d), 69.2
(s), 84.5 (t), 88.0 (s), 120.0 (s), 128.4 (d × 2), 128.9 (d × 2), 131.2
(d × 2), 131.4 (d × 2), 134.8 (d), 135.1 (d), 135.5 (s) and 137.2
(s); m/z 430 (M+) and 125 (base) (Found: C, 58.42; H, 5.18; N,
6.74. C21H22N2O4S2 requires C, 58.59; H, 5.15; N, 6.51%).
5,5-Bis(phenylsulfonyl)-4-phenylethynyl-4,5-dihydro-3H-
pyrazole 19. Colourless prisms (from CHCl3–Et2O), mp 104–
106 ЊC (decomp.); νmax/cmϪ1 1350 and 1160 (SO2); δH (270 MHz,
CDCl3) 4.00 (1 H, t, J 9, 4-H), 4.77 (1 H, dd, J 9 and 18, 3-H),
5.31 (1 H, dd, J 9 and 18, 3-H), 7.22–7.35 (5 H, m, ArH), 7.46–
7.57 (4 H, m, ArH), 7.63–7.71 (2 H, m, ArH), 7.89–7.93 (2 H,
m, ArH) and 8.03–8.06 (2 H, m, ArH); δC(67.5 MHz, CDCl3)
31.4 (d), 79.3 (s), 84.4 (t), 87.0 (s), 120.8, (s), 122.2 (s), 128.2
(d × 2), 128.5 (d × 2), 128.6 (d), 129.0 (d × 2), 131.3 (d × 2),
131.5 (d × 2), 131.7 (d × 2), 135.0 (d), 135.3 (d), 135.5 (s) and
137.1 (s); m/z 422 (M+ Ϫ N2) and 281 (base) (Found: C, 61.29;
H, 4.03; N, 6.21. C23H18N2O4S2 requires C, 61.32; H, 4.03; N,
6.22%).
4-(2-Phenylethynyl)-3-phenylsulfonyl-4,5-dihydro-1H-
pyrazole 13. Colourless prisms (from CHCl3–Et2O), mp 120–
121 ЊC; νmax/cmϪ1 3375 (NH), 2200 (acetylene) and 1300 and
1150 (SO2); δH (270 MHz, CDCl3) 3.95 (1 H, t, J 12, 4-H), 4.35
(1 H, dd, J 4 and 12, 5-H), 4.61 (1 H, dd, J 4 and 12, 5-H), 7.29–
7.43 (5 H, m, ArH), 7.48–7.54 (2 H, m, ArH), 7.61–7.66 (1 H,
m, ArH) and 8.00–8.03 (2 H, m, ArH); δC(67.5 MHz, CDCl3)
50.4 (t), 72.1 (d), 81.3 (s), 95.2 (s), 121.7 (s), 128.2 (s), 128.3
(d × 2), 128.9 (d × 2), 129.1 (d), 129.4 (d × 2), 131.7 (d × 2),
134.3 (d) and 137.1 (s); m/z 308 (M+ Ϫ 2) and 83 (base) (Found:
C, 65.76; H, 4.53; N, 8.93. C17H14N2O2S requires C, 65.79; H,
4.55; N, 9.03%).
(4S*,5R*)-5-(Hex-1-ynyl)-5-methyl-4-phenylsulfonyl-4,5-
dihydro-3H-pyrazole 14. A colourless oil; νmax/cmϪ1 2250
(acetylene) and 1330 and 1160 (SO2); δH (270 MHz, CDCl3)
0.87 (3 H, t, J 7, CH3), 1.27–1.42 (4 H, m, CH2CH2), 1.81 (3
H, s, CH3), 2.12 (2 H, t, J 7, 3Ј-H), 3.71 (1 H, t, J 8, 4-H),
4.73–4.93 (2 H, m, 3-H), 7.60–7.90 (3 H, m, ArH) and 7.91–
7.92 (2 H, m, ArH); δC(67.5 MHz, CDCl3) 13.3 (q), 18.1 (t),
20.4 (q), 21.6 (t), 30.0 (t), 65.5 (d), 76.5 (t), 78.3 (s), 85.7 (s),
88.2 (s), 127.8 (d × 2), 129.3 (d × 2), 134.0 (d) and 139.3 (s)
[Found (FABMS): (M + 1)+, 305.1331. C16H20N2O2S requires
M + 1, 305.1324].
(4R*,5S*)-4-(3,3-Dimethylbut-1-ynyl)-5-phenethyl-5-phenyl-
sulfonyl-4,5-dihydro-3H-pyrazole 15. Colourless needles (from
CHCl3–Et2O), mp 106–107 ЊC; νmax/cmϪ1 2250 (acetylene) and
1310 and 1150 (SO2); δH (270 MHz, CDCl3) 1.45 (9 H, s,
CH3 × 3), 2.26 (1 H, dt, J 6 and 12, PhCH2CH2), 2.52–2.61 (2
H, m, PhCH2CH2), 2.78 (1 H, dt, J 6 and 12, PhCH2CH2), 3.79
(1 H, dd, J 7 and 10, 4-H), 4.54 (1 H, dd, J 7 and 18, 3-H), 5.09
(1 H, dd, J 10 and 18, 3-H), 7.06–7.08 (2 H, m, ArH), 7.12–7.26
(3 H, m, ArH), 7.52–7.62 (2 H, m, ArH), 7.70–7.72 (1 H, m,
ArH) and 7.96–7.98 (2 H, m, ArH); δC(67.5 MHz, CDCl3) 27.4
(d), 27.5 (s), 29.1 (t), 30.9 (q × 3), 32.2 (t), 73.1 (s), 85.5 (t), 93.9
(s), 112.7 (s), 126.3 (d), 128.0 (d × 2), 128.5 (d × 2), 129.2
(d × 2), 130.6 (d × 2), 134.6 (d), 135.3 (s) and 140.2 (s); m/z 393
(M+ Ϫ 1) and 252 (base) (Found: C, 69.86; H, 6.72; N, 6.97.
C23H26N2O2S requires C, 70.07; H, 6.65; N, 7.10%).
4-(3,3-Dimethylbut-1-ynyl)-5-phenethyl-1H-pyrazole 16.
Colourless needles (from CH2Cl2–hexane), mp 107–110 ЊC;
νmax/cmϪ1 3170 and 3130 (NH); δH (270 MHz, CDCl3) 1.32 (9 H,
s, CH3 × 3), 3.01 (4 H, s, CH2CH2), 7.19–7.21 (2 H, m, ArH),
7.26–7.29 (3 H, m, ArH) and 7.52 (1 H, s, 3-H); δC(67.5 MHz,
CDCl3) 28.0 (t), 28.1 (s), 31.2 (q × 3), 34.7 (t), 69.6 (s), 101.2 (s),
102.2 (s), 126.2 (d × 2), 128.4 (d × 2), 128.5 (d × 2), 136.7 (s)
4-(3,3-Dimethylbut-1-ynyl)-1-methyl–5-phenylsulfonyl-
pyrazole 20. A yellow oil; νmax/cmϪ1 2250 (acetylene) and 1340
and 1140 (SO2); δH (270 MHz, CDCl3) 1.34 (9 H, s, CH3 × 3),
4.14 (3 H, s, CH3), 7.47 (1 H, s, 3-H), 7.53–7.57 (2 H, m, ArH),
7.63–7.66 (1 H, m, ArH) and 8.05–8.07 (2 H, m, ArH); δC(67.5
MHz, CDCl3) 28.2 (s), 30.6 (q × 3), 40.0 (q), 68.0 (s), 104.7 (s),
109.3 (s), 127.3 (d × 2), 129.2 (d × 2), 134.0 (d), 139.4 (s), 141.0
(s) and 141.2 (d) (Found: M+, 302.1077. C16H18N2O2S requires
M, 302.1089).
4-(3,3-Dimethylbut-1-ynyl)-1-methyl–3-phenylsulfonyl-
pyrazole 21. Colourless prisms (from CH2Cl2–hexane), mp 103–
104 ЊC; νmax/cmϪ1 2250 (acetylene) and 1320 and 1150 (SO2);
δH (270 MHz, CDCl3) 1.37 (9 H, s, CH3 × 3), 3.83 (3 H, s, CH3),
7.48–7.52 (2 H, m, ArH), 7.56–7.58 (1 H, m, ArH), 7.86 (1 H, s,
5-H) and 8.00–8.02 (2 H, m, ArH); δC(67.5 MHz, CDCl3) 29.2
(s), 30.9 (q × 3), 38.3 (q), 65.8 (s), 113.6 (s), 125.4 (s), 128.0
(d × 2), 128.2 (s), 129.5 (d × 2), 133.6 (d), 139.4 (d) and 143.1
(s); m/z 302 (M+, base) (Found: C, 63.35; H, 6.01; N, 9.29.
C16H18N2O2S requires C, 63.55; H, 6.00; N, 9.26%).
(4S*,5S*)-4-(3,3-Dimethylbut-1-ynyl)-5-phenylethynyl-5-
phenylsulfonyl-4,5-dihydro-3H-pyrazole 33. Colourless prisms
(from CHCl3–hexane), mp 113–117 ЊC; νmax/cmϪ1 2210 (acetyl-
ene) and 1325 and 1150 (SO2); δH (270 MHz, CDCl3) 1.11 (9 H,
s, CH3 × 3), 3.83 (1 H, dd, J 5 and 9, 4-H), 4.85 (1 H, dd, J 5 and
18, 3-H), 5.14 (1 H, dd, J 9 and 18, 3-H), 7.29–7.36 (5 H, m,
ArH), 7.57–7.62 (2 H, m, ArH), 7.71–7.74 (1 H, m, ArH) and
8.06–8.09 (2 H, m, ArH); δC(67.5 MHz, CDCl3) 27.3 (s), 29.9
(t), 30.8 (q × 3), 73.6 (s), 78.1 (s), 86.3 (d), 94.0 (s), 95.4 (s),
100.6 (s), 121.0 (s), 128.3 (d × 2), 128.8 (d × 2), 129.5 (d), 130.9
698
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(d × 2), 131.7 (d × 2), 134.8 (d) and 135.2 (s); m/z 362 (M+), 362
(base) (Found: C, 70.87; H, 5.75; N, 7.27. C23H22N2O2S requires
C, 70.74; H, 5.69; N, 7.17%).
(s), 101.5 (s), 129.2 (d), 129.3 (d) and 130.7 (s) (Found: M+,
148.1003. C9H12N2 requires M, 148.1001).
4-Phenylethynyl-1H-pyrazole 25. Colourless needles (from
CH2Cl2–hexane), mp 99–101 ЊC; νmax/cmϪ1 3150 (NH); δH (270
MHz, CDCl3) 6.55 (1 H, d, J 2, pyrazole H), 7.33–7.34 (3 H, m,
ArH), 7.52–7.54 (2 H, m, ArH) and 7.63 (1 H, d, J 2, pyrazole
H); δC(67.5 MHz, CDCl3) 77.2 (s), 80.6 (s), 91.3 (s), 109.3 (d),
122.5 (s), 128.4 (d × 2), 128.6 (d), 131.6 (d × 2) and 132.5 (d);
m/z 168 (M+, base) (Found: C, 78.30; H, 4.89; N, 16.53.
C11H8N2 requires C, 78.55; H, 4.79; N, 16.65%).
4-(3,3-Dimethylbut-1-ynyl)-5-phenylethynyl-1H-pyrazole 34.
Colourless prisms (from CH2Cl2–hexane), mp 139–141 ЊC; νmax
/
cmϪ1 3150 (NH) and 2200 (acetylene); δH (270 MHz, CDCl3)
1.34 (9 H, s, CH3 × 3), 7.32–7.34 (3 H, m, ArH), 7.52–7.54 (2
H, m, ArH) and 7.66 (1 H, s, 3-H); δC(67.5 MHz, CDCl3) 28.2
(s), 31.0 (q × 3), 68.9 (s), 78.8 (s), 94.8 (s), 102.4 (s), 108.0 (s),
122.4 (s), 128.3 (d × 2), 128.7 (d), 131.7 (d × 2), 133.5 (s) and
135.1 (d); m/z 248 (M+) and 233 (base) (Found: C, 82.42; H,
6.61; N, 11.23. C17H16N2 requires C, 82.22; H, 6.49; N, 11.28%).
(4S*,5S*)-4-(Hex-1-ynyl)-5-phenylethynyl–5-phenylsulfonyl-
4,5-dihydro-3H-pyrazole 36. Colourless prisms (from CH2Cl2–
hexane), mp 67–68 ЊC; νmax/cmϪ1 2250 (acetylene) and 1330 and
1160 (SO2); δH (270 MHz, CDCl3) 0.78 (3 H, t, J 7, CH3), 1.24–
1.43 (4 H, m, CH2CH2), 2.15 (2 H, dt, J 2 and 7, 3Ј-H), 3.82–
3.87 (1 H, m, 4-H), 4.86 (1 H, dd, J 5 and 18, 3-H), 5.15 (1 H,
dd, J 9 and 18, 3-H), 7.26–7.38 (5 H, m, ArH), 7.55–7.63 (2 H,
m, ArH), 7.73–7.77 (1 H, m, ArH) and 8.08–8.10 (2 H, m,
ArH); δC(67.5 MHz, CDCl3) 13.5 (q), 18.5 (t), 21.9 (t), 30.1 (d),
30.7 (t), 75.0 (s), 78.1 (s), 86.0 (s), 86.0 (t), 95.8 (s), 109.5 (s),
121.1 (s), 128.4 (d × 2), 128.9 (d × 2), 129.6 (d), 131.0 (d × 2),
131.8 (d × 2), 134.9 (d) and 135.3 (s); m/z 390 (M+) and 178
(base) (Found: C, 70.75; H, 5.74; N, 7.21. C23H22N2O2S requires
C, 70.74; H, 5.69; N, 7.17%).
4-(3,3-Dimethylbut-1-ynyl)-5-phenylsulfonyl-1H-pyrazole 26.
Colourless needles (from CHCl3–Et2O), mp 170–172 ЊC; νmax
/
cmϪ1 3150 (NH), 2250 (acetylene) and 1340 and 1160 (SO2);
δH (270 MHz, CDCl3) 1.34 (9 H, s, CH3 × 3), 7.49–7.53 (2 H, m,
ArH), 7.60–7.64 (1 H, m, ArH), 8.06–8.08 (2 H, m, ArH) and
8.16 (1 H, s, 3-H); δC(67.5 MHz, CDCl3) 28.1 (s), 30.7 (q × 3),
67.1 (s), 103.8 (s), 104.6 (s), 127.9 (d × 2), 129.0 (d × 2), 133.7
(d), 136.2 (d), 140.3 (s) and 150.9 (s) (Found: M+, 288.0922.
C15H16N2O2S requires M, 288.0932).
1,1-Bis(phenylsulfonyl)-2-(3,3-dimethylbut-1-ynyl)cyclo-
propane 27. Colourless prisms (from CH2Cl2–hexane), mp 119–
121 ЊC; νmax/cmϪ1 2250 (acetylene) and 1320 and 1160 (SO2);
δH (270 MHz, CDCl3) 1.24 (9 H, s, CH3 × 3), 2.00 (1 H, dd, J 6
and 10, 3-H), 2.38 (1 H, dd, J 6 and 8, 3-H), 3.27 (1 H, dd, J 8
and 10, 2-H), 7.52–7.56 (4 H, m, ArH), 7.65–7.68 (2 H, m,
ArH), 7.91–7.93 (2 H, m, ArH) and 8.27–8.29 (2 H, m, ArH);
δC(67.5 MHz, CDCl3) 18.3 (d), 20.7 (t), 27.6 (s), 30.5 (q × 3),
63.6 (s), 71.8 (s), 93.2 (s), 128.4 (d × 2), 128.8 (d × 2), 129.6
(d × 2), 129.7 (d × 2), 134.1 (d), 134.3 (d), 138.2 (s) and 139.1 (s)
(Found: M+, 402.0942. C21H22O4S2 requires M, 402.0960).
4-(Hex-1-ynyl)-5-phenylsulfonyl-1H-pyrazole 28. Colourless
needles (from CHCl3–Et2O), mp 96–98 ЊC; νmax/cmϪ1 3100
(NH), 2200 (acetylene) and 1300 and 1100 (SO2); δH (270 MHz,
CDCl3) 0.96 (3 H, t, J 7, CH3), 1.40–1.66 (4 H, m, CH2CH2),
2.44 (2 H, t, J 7, 3Ј-H), 7.48–7.54 (2 H, m, ArH), 7.59–7.65 (1
H, m, ArH), 8.03–8.06 (2 H, m, ArH) and 8.12 (1 H, s, 3-H)
(Found: M+, 288.0921. C15H16N2O2S requires M, 288.0932).
1,1-Bis(phenylsulfonyl)-2-(hex-1-ynyl)cyclopropane 29. White
prisms (from CH2Cl2–hexane), mp 68–71 ЊC; νmax/cmϪ1 2250
(acetylene) and 1330 and 1160 (SO2); δH (270 MHz, CDCl3) 0.90
(3 H, t, J 7, CH3), 1.36–1.52 (4 H, m, CH2CH2), 2.01 (1 H, dd, J
6 and 10, 3-H), 2.17–2.21 (2 H, m, 3Ј-H), 2.39 (1 H, dd, J 6 and
8, 3-H), 3.23–3.27 (1 H, m, 2-H), 7.52–7.58 (4 H, m, ArH),
7.65–7.70 (2 H, m, ArH), 7.95–7.96 (2 H, m, ArH) and 8.23–
8.25 (2 H, m, ArH); δC(67.5 MHz, CDCl3) 13.5 (q), 18.2 (d),
18.7 (t), 20.9 (t), 21.9 (t), 30.3 (t), 63.0 (s), 72.6 (s), 85.6 (s), 128.3
(d × 2), 128.8 (d × 2), 129.8 (d × 2), 129.9 (d × 2), 134.2 (d),
134.4 (d), 138.4 (s) and 138.9 (s) (Found: M+, 402.0945.
C21H22O4S2 requires M, 402.0960).
4-Phenylethynyl-5-phenylsulfonyl-1H-pyrazole 30. Colourless
needles (from CHCl3–Et2O), mp 178–180 ЊC; νmax/cmϪ1 3150
(NH), 2225 (acetylene) and 1320 and 1150 (SO2); δH (270 MHz,
CDCl3) 7.38–7.40 (3 H, m, ArH), 7.49–7.56 (4 H, m, ArH),
7.60–7.64 (1 H, m, ArH), 8.10–8.12 (2 H, m, ArH) and 8.27 (1
H, s, 3-H); δC(67.5 MHz, CDCl3) 77.2 (s), 94.8 (s), 104.1 (s),
122.6 (s), 128.1 (d × 2), 128.5 (d × 2), 128.8 (d), 129.2 (d × 2),
131.5 (d × 2), 134.0 (d), 136.3 (d), 140.0 (s) and 151.4 (s); m/z
308 (M+, base) (Found: C, 66.02; H, 4.00; N, 9.04. C17H12N2O2S
requires C, 66.22; H, 3.92; N, 9.08%).
1,1-Bis(phenylsulfonyl)-2-phenylethynylcyclopropane 31. Yel-
low prisms (from CH2Cl2–hexane), mp 41–42 ЊC; νmax/cmϪ1
2250 (acetylene) and 1330 and 1160 (SO2); δH (270 MHz,
CDCl3) 2.13 (1 H, dd, J 6 and 10, 3-H), 2.56 (1 H, dd, J 6 and 8,
3-H), 3.47 (1 H, dd, J 8 and 10, 2-H), 7.31–7.38 (3 H, m, ArH),
7.42–7.45 (4 H, m, ArH), 7.57–7.64 (3 H, m, ArH), 7.69–7.73 (1
H, m, ArH), 8.00–8.02 (2 H, m, ArH) and 8.24–8.26 (2 H, m,
ArH) (Found: M+, 422.0625. C23H18O4S2 requires M, 422.0646).
4-(Hex-1-ynyl)-5-phenylethynyl-1H-pyrazole 37. Colourless
needles (from CHCl3–Et2O), mp 56–58 ЊC; νmax/cmϪ1 3175 (NH),
2225 (acetylene) and 1340 and 1150 (SO2); δH (270 MHz,
Cyclopropanations of the pyrazoles 12 and 14
We performed the cyclopropanations of 12 and 14 by the gen-
eral procedure described by Padwa.7
(1S*,2R*)-2-(3,3-Dimethylbut-1-ynyl)-1–phenylsulfonylcyclo-
propane 22. Colourless needles (from CH2Cl2–hexane), mp 99–
100 ЊC; νmax/cmϪ1 2225 (acetylene) and 1325 and 1150 (SO2);
δH (270 MHz, CDCl3) 1.13 (9 H, s, Me × 3), 1.24 (1 H, ddd, J 5
and 9 and 10, 3-H), 1.58 (1 H, ddd, J 6 and 9 and 10, 3-H), 2.25
(1 H, ddd, J 4 and 6 and 9, 2-H), 2.65 (1 H, ddd, J 4 and 5 and 9,
1-H), 7.54–7.59 (2 H, m, ArH), 7.62–7.66 (1 H, m, ArH) and
7.88–7.91 (2 H, m, ArH); δC(67.5 MHz, CDCl3) 8.8 (d), 14.8 (t),
27.1 (s), 30.8 (q × 3), 40.7 (d), 75.6 (s), 87.7 (s), 127.5 (d × 2),
129.2 (d × 2), 133.5 (d) and 140.1 (s); m/z 262 (M+) and 93
(base) (Found: C, 68.65; H, 6.95. C15H18O2S requires C, 68.67;
H, 6.92%).
(1S*,2R*)-2-(Hex-1-ynyl)-2-methyl-1-phenylsulfonylcyclo-
propane 23. A colourless oil; νmax/cmϪ1 2225 (acetylene) and
1310 and 1150 (SO2); δH (270 MHz, CDCl3) 0.87 (3 H, t, J 7,
Me), 1.23–1.44 (4 H, m, alkyl H), 1.48 (1 H, dd, J 5 and 9, 3-H),
1.61 (1 H, dd, J 5 and 7, 3-H), 1.62 (3 H, s, Me), 2.06 (2 H, t, J 7,
CH2), 2.69 (1 H, dd, J 7 and 9, 1-H), 7.66–7.68 (3 H, m, ArH)
and 7.90–7.94 (2 H, m, ArH); δC(67.5 MHz, CDCl3) 13.5 (q),
18.1 (q), 18.1 (t), 21.5 (t), 21.8 (t), 30.6 (t), 45.4 (d), 78.5 (s), 82.7
(s), 127.2 (d × 2), 129.2 (d × 2), 133.3 (d) and 141.5 (s); m/z 135
(base) (Found: C, 69.66; H, 7.36. C16H20O2S requires C, 69.53;
H, 7.29%).
Dehydrosulfonylation of the pyrazolines 12–19 with MeLi
Typical procedure. An ether solution of MeLi (1 cm3, 1.0
mmol) was added dropwise to a THF (2 cm3) solution of
the pyrazoline 12 (145 mg, 0.5 mmol) at Ϫ78 ЊC. The reac-
tion mixture was stirred for 10 min after which saturated aque-
ous NH4Cl was added to the mixture. The organic layer was
separated and the aqueous layer was extracted with ether. The
organic layer and the extracts were combined, dried (MgSO4)
and evaporated under reduced pressure. The residue was puri-
fied by preparative TLC on silica gel eluting with AcOEt–
hexane (1:10) to give 4-(3,3-dimethylbut-1-ynyl)-1H-pyrazole
24 (59 mg, 80%) as colourless prisms after recrystallization
from CH2Cl2–hexane; mp 160–163 ЊC; νmax/cmϪ1 3150 (NH)
and 2250 (acetylene); δH (270 MHz, CDCl3) 1.32 (9 H, s,
CH3 × 3), 6.37 (1 H, d, J 2, pyrazole H) and 7.54 (1 H, d, J 2,
pyrazole H); δC(67.5 MHz, CDCl3) 28.0 (s), 30.7 (q × 3), 69.5
J. Chem. Soc., Perkin Trans. 1, 1997
699

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I. R. Silverman, P. S. Ray, T. G. Cullen, S. F. Ali, F. L. Marek and
CDCl3) 0.93 (3 H, t, J 7, CH3), 1.47–1.64 (4 H, m, CH2CH2),
2.45 (2 H, t, J 7, 3Ј-H), 7.32–7.35 (3 H, m, ArH), 7.53–7.55 (2
H, m, ArH) and 7.65 (1 H, s, 3-H); δC(67.5 MHz, CDCl3) 13.6
(q), 19.3 (t), 21.9 (t), 30.8 (t), 70.3 (s), 78.5 (s), 94.2 (s), 94.9 (s),
108.0 (s), 122.3 (s), 128.3 (d × 2), 128.8 (d) and 131.8 (d × 3)
and 136.2 (s); m/z 248 (M+, base) (Found: C, 82.01; H, 6.41; N,
11.17. C17H16N2 requires C, 82.22; H, 6.50; N, 11.28%).
C. A. Webster, Agrochemicals III, ed. D. R. Baker, J. G. Fenyes and
J. J. Steffens, ACS Symposium Series 504, 1992, ch. 28, p. 313.
2 S. D. Karanewsky, M. C. Badia, S. A. Biller, E. M. Gordon and
M. J. Sofia, (Ger. Offen. DE) USP. 3 817 298, 1987.
3 L. V. Quang and Y. V. Quang, Bull. Chem. Soc. Fr., Pt. 2, 1974, 11,
2575.
4 M. F. Ford and D. R. M. Walton, Synthesis, 1973, 47.
5 I. V. Finar and E. Okoh, J. Chem. Soc., Perkin Trans. 1, 1973, 2008.
6 M. Yoshimatsu, M. Kawahigashi, H. Shimizu and T. Kataoka,
J. Chem. Soc., Chem. Commun., 1995, 583; M. Hofmann and
N. Krause, Chem. Ber., 1995, 128, 851.
7 A. Padwa and M. W. Wannamaker, Tetrahedron, 1991, 47, 6139.
8 K. N. Houk, Acc. Chem. Res., 1975, 8, 361; T. Minato, S. Yamabe,
S. Inagaki, H. Fujimoto and K. Fukui, Bull. Chem. Soc. Jpn., 1974,
47, 1619.
9 M. Yoshimatsu and J. Hasegawa, J. Chem. Soc., Perkin Trans. 1,
1997, 211.
Acknowledgements
Molecular orbital calculations were performed by Professor
Satoshi Inagaki and Associate Professor Masaru Ishida in
the Department of Chemistry, Faculty of Industry, Gifu
University.
10 F. Arndt, Org. Synth., Coll. Vol. II, 1943, 165, 461.
References
1 M. P. Lynch, J. R. Beck, E. V. P. Tao, J. Aikins, G. E. Babbitt,
J. R. Rizzo and T. W. Waldrep, Synthesis and Chemistry of
Agrochemicals II, ed. D. R. Baker, J. G. Fenyes and W. K. Moberg,
ACS Symposium Series 443, 1991, ch. 12, p. 144; G. A. Meier,
Paper 6/05542G
Received 8th August 1996
Accepted 21st October 1996
700
J. Chem. Soc., Perkin Trans. 1, 1997