Synthesis of pyrazolidine, 1-pyrazoline, 2-pyrazoline derivatives by selenium-induced cyclization of homoallylhydrazines

Article abstract of DOI:10.1016/S0040-4020(01)01064-X

The PhSeBr-induced cyclization of N′-but-3-en-1-yl ethoxycarbonylhydrazines 1, phenylhydrazines 2 and dimethylhydrazines 3 has been studied. A 5-exo-trig ring closure occurred in each case and phenylselanylmethyl-pyrazolidines 4, 2-pyrazolines 5 and 10, 1-pyrazolines 8 and pyrazolidinium bromides 11 were synthesized. Radical deselenenylation has allowed the preparation of 5-methylpyrazolidines 12 and 5-methyl-2-pyrazolines 13 and 14. Decomposition of the dibromoselenuranes derived from 2-pyrazolines 5 and 10 afforded bromomethyl derivatives. With 1-phenyl-2-pyrazolines 10, an electrophilic p-halogenation of the phenyl nucleus was observed.

Full text of DOI:10.1016/S0040-4020(01)01064-X

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 10259±10270
Synthesis of pyrazolidine, 1-pyrazoline, 2-pyrazoline derivatives
by selenium-induced cyclization of homoallylhydrazines
p
È
Michael Ternon, Francis Outurquin and Claude Paulmier
Á Â Â Â
Laboratoire de Synthese Thio- and Seleno-organique, IRCOFÐUniversite de Rouen, UFR des Sciences et des Techniques,
F-76821 Mont-Saint-Aignan cedex, France
Received 26 July 2001;revised 3 October 2001;accepted 30 October 2001
AbstractÐThe PhSeBr-induced cyclization of N0-but-3-en-1-yl ethoxycarbonylhydrazines 1, phenylhydrazines 2 and dimethylhydrazines 3
has been studied. A 5-exo-trig ring closure occurred in each case and phenylselanylmethyl-pyrazolidines 4, 2-pyrazolines 5 and 10,
1-pyrazolines 8 and pyrazolidinium bromides 11 were synthesized. Radical deselenenylation has allowed the preparation of 5-methyl-
pyrazolidines 12 and 5-methyl-2-pyrazolines 13 and 14. Decomposition of the dibromoselenuranes derived from 2-pyrazolines 5 and 10
afforded bromomethyl derivatives. With 1-phenyl-2-pyrazolines 10, an electrophilic p-halogenation of the phenyl nucleus was observed.
q 2001 Elsevier Science Ltd. All rights reserved.
The selenium-induced cyclofunctionalization of unsaturated
alcohols and carboxylic acids is now an ef®cient method for
the synthesis of cyclic ethers and lactones.1,2 N-protected
alkenyl amines have been successfully cyclized into aza-
heterocycles.1±3 In these reactions, a seleniranium inter-
mediate is involved and the attack of the internal
nucleophile occurs with stereospeci®c anti-addition.
According to the Baldwin's rules,4 the exo-trig ring closures
are favored, especially with substrates bearing a terminal
ole®nic bond. In these conditions, 1-alkoxycarbonyl-2-
phenylselanylmethyl-pyrrolidines,2 and -piperidines,3 have
been synthesized. As a consequence of a competitive mono-
and di-selenenylation of the amino group,5 alkenyl primary
amines cannot be cyclized, but secondary pent-4-en-1-
ylamines afforded, under acidic conditions and with
modest yields, 1,2-dialkyl-5-phenylselanylmethylpyrro-
lidines according to a 5-exo-trig ring closure.6
In a recent study of the laboratory,7,8 we observed that
competitive 4-exo-trig and 5-endo-trig processes occurred
in the PhSeX-induced cyclization of N-benzyl homoallylic
amines I (Scheme 1). The reaction was carried out in
CH3CN containing sodium carbonate. Mixtures of phenyl-
selanylpyrrolidines II and phenylselanylmethylazetidines
Scheme 1.
Keywords: pyrazolidine;cyclization;homoallylhydrazines.
Corresponding author. Tel.: 133-2-35-52-29-50;fax: 133-2-35-52-29-59;e-mail: claude.paulmier@univ-rouen.fr
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)01064-X

10260
M. Ternon et al. / Tetrahedron 57 (2001) 10259±10270
Scheme 2.
III were obtained as their HX salts in absence of sodium
carbonate.8 The formation of azetidines was observed for
the ®rst time by this ring closure process. The ratio of azeti-
dines increased according to the order: PhSeCl,Ph-
SeBr,PhSeI and with the size of the a-substituent
(R2ˆH). A geminal a-effect (R2±H) led dramatically to
the major formation (.80%) of the azetidine derivatives
III.7,8 With an excess of PhSeX (XˆCl, Br), the b-halo-
pyrrolidines IV were isolated with good yields.7,9
selenium-induced cyclization of `homoallyl' or but-3-en-1-
ylhydrazine derivatives 1 (NHCOOEt), 2 (NHPh) and 3
(NMe2).
Tiecco et al.10 have studied the phenylselenenyl sulfate-
induced cyclization of N0-allylic acetylhydrazines V,
As an extension of this work, we were then interested in the
Scheme 3.
Table 1.
Substrate
R1
Composition (%)
Isolated yield (%)
PhSeBr excess 5 yield (%)
1
4
5
4
5
1a
1b
1c
1d
Ph
Et
iPr
Bn
50
20
20
10
±
50
40
40
45
±
42
68
67
70
73
82
70
73
40
40
45
,10
,10
,10

M. Ternon et al. / Tetrahedron 57 (2001) 10259±10270
10261
Scheme 4.
Table 2.
Substrate
R1
R2
Composition (%)
Isolated yield (%)
PhSeBr excess 8 yield (%)
1
4
8
4
8
1e
1f
1g
Et
Et
Et
Me
Ph
Et
10
10
20
50
75
50
40
15
30
49
72
45
21
,10
20
85
64
76
under acidic conditions (Scheme 2). With the simple allyl
substituent, a 1,3,4-oxadiazine VI was formed as a con-
sequence of the ambident nucleophilic nature of the
NHCOMe group. When the reaction was carried out on
substrates with a more substituted allyl group, the N-acetyl
pyrazolidine VII was isolated as the thermodynamic
product.
were used for the selenium-induced cyclization of homo-
allylic amines.1,2
The hydrazine derivative 1a (R1ˆPh, R2ˆH) afforded the
2-pyrazoline 5a in mixture with the substrate. Using an
excess of PhSeBr (3 equiv.), 5a was isolated with 73%
yield (Scheme 3, Table 1). The other hydrazine derivatives
1b±d (R2ˆH), bearing an a-alkyl group, have led to
mixtures of pyrazolidine 4, 2-pyrazoline 5 and amine 1.
An excess of selenium reagent produced 5 in good yields.
As shown in Scheme 3, this result seems to indicate that a
selenenamide 6 undergoes a selenophilic reaction with
PhSeBr. The presence of the good leaving group in 7 allows
the formation of the iminyl double bond. The sequence
4!6!7!5 must occur faster that the cyclization step.
Tiecco et al.11 have observed that hexahydropyridazines
are easily oxidized into tetrahydropyridazines during the
work-up and the chromatography on silica gel.
The same group has also investigated the selenium-induced
cyclization of N0-pent-4-en-1-yl hydrazine derivatives VIII
(RˆPh, COOEt, COMe, Ts).11 As shown in Scheme 2, the
nucleophilic center depends on the nature of R. The 5-exo-
trig. mode was ef®cient with electron-withdrawing groups
(RˆCOMe, Ts) affording the pyrrolidinamine IX. The 6-
exo-trig cyclization was favored with RˆPh. The hexa-
hydropyridazine derivatives X were partially oxidized into
tetrahydropyridazine derivatives XI during the work-up.
The other substrates 1e±g (R1, R2±H) were then considered
(Scheme 4, Table 2). Surprisingly, the 1-pyrazine deriva-
tives 8 were obtained beside the pyrazolidine 4, and
unreacted amine 1. They could be isolated in a pure form.
Here, also, an excess of PhSeBr (3 equiv.) gave the 1-pyra-
zine 8 in a good yield. (Table 2). We suggest that 4 afforded
the selenenamide intermediate 6 (R2±H) allowing the
1.Results and discussion
The substrates 1±3, were prepared by reductive allylation
(Allylmagnesium chloride, THF, 2788C) of the correspond-
ing hydrazones. They were then treated with PhSeBr
(1.5 equiv.) in MeCN, at room temperature, in the presence
of sodium carbonate. The same experimental conditions
Scheme 5.

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M. Ternon et al. / Tetrahedron 57 (2001) 10259±10270
Scheme 6.
appearance of the selanylselenonium salt 7 (R2±H). The
2-pyrazoline cannot be formed and bromide ion displaces
the carboxylate from the ester group. The loss of CO2 and
ethyl bromide allows the formation of the nitrogen±nitrogen
double bond (Scheme 4).
The phenylselanylmethyl pyrazolidines 4e±g, 2-pyrazolines
5a±d (RˆCOOEt) and 10a±d (RˆPh) were then subjected
to the radical deselenenylation using a classical route. The
5-methylpyrazolidines 12e±g, 5-methyl-2-pyrazolidines
13a±d (RˆCOOEt) and 14a±d (RˆPh) were synthesized
in good yields (Scheme 7).
The treatment of the phenylhydrazines 2a±d by PhSeBr
(1.5 equiv.), under the same conditions, has led to the iso-
lation of the 1-phenyl-2-pyrazolines 10, in very good yields
(Scheme 5). The corresponding pyrazolidines 9 were not
detected and were easily oxidized into 2-pyrazolines 10.
An analogous observation was made by Tiecco et al.11
during the transformation of N-phenyl hexahydropyrida-
zines into tetrahydropyridazines.
Examination of the literature has shown that the synthesis of
pyrazolidines was not extensively studied,12 if we except the
work of Tiecco et al.10 The same observation can be made
for the access to 1-pyrazolines13 and 2-pyrazolines.14
Our interest for the reactivity of Se-dihalo adducts derived
from functionalized and unsaturated phenylselenides15 led
us to study the reaction of the 2-pyrazolines 5 (RˆCOOEt)
and 10 (RˆPh) with SO2Cl2 or Br2.
The dichloroselenuranes 15b (R1ˆEt) and 15c (R1ˆiPr)
were immediately formed in CCl4 at room temperature
and were not decomposed on heating in the same solvent.
The reaction of the N,N-dimethylhydrazines 3a±c, with
PhSeBr, has allowed the formation of the 1,1-dimethyl-
pyrazolidinium bromides 11a±c in correct yields (Scheme
6). The 5-exo-trig mode was still ef®cient. Starting from
substrates 1±3, the 4-exo-trig ring closure was not observed.
Scheme 7.
Scheme 8.

M. Ternon et al. / Tetrahedron 57 (2001) 10259±10270
10263
Scheme 9.
On the contrary, the dibromo adduct 16b (R1ˆEt) afforded
the 5-bromomethyl-2-pyrazoline 17b (51%) and the
5-bromomethylpyrazole 18b (15%). The pyrazole 18b
must be the oxidation product resulting from the reaction
of 17b with bromine16 (Scheme 8).
adducts 19 (XˆCl) and 20 (XˆBr) derived from 1-phenyl-
2-pyrazolines 10. The 5-bromomethyl-1-p-bromophenyl
pyrazole 24a and 1-p-halophenyl-5-phenylselanylmethyl-
2-pyrazolines 21b,c (XˆCl) and 22b,c (XˆBr) were the
major products formed.
The 1-phenyl-5-phenylselanylmethyl-2-pyrazolines 10a±c
gave unstable dihalo adducts 19 (XˆCl) and 20 (XˆBr)
which were decomposed on heating. An unexpected para-
halogenation of the N-phenyl nucleus was observed when
R1 was an alkyl group. The 1-p-chlorophenyl- and 1-p-
bromophenyl-5-phenylselanylmethyl-2-pyrazolines 21 and
22 were respectively isolated (Scheme 9). The p-bromo-
phenyl derivative 22b (R1ˆEt, 54% yield) was formed
along with the 1-p-bromophenyl-5-bromomethyl-2-pyrazo-
line 23b and the corresponding pyrazole 24b as minor
product. The 5-bromomethyl-1-p-bromophenyl-3-phenyl-
pyrazole 24a was only isolated, in 45% yield, after decom-
position of the dibromoselenurane 20a (R1ˆPh). In these
reactions, the dihaloselenurane 19 (or 20) behaves mainly
as a good electrophilic halogenating source, in the reaction
with the N-activated phenyl group. Compounds 21 and 22
(R1ˆalkyl) must be the kinetic products.
2.Experimental
Ethoxycarbonylhydrazones,17 phenylhydrazones18 and
dimethylhydrazones19 were prepared by classical methods.
THF was distilled over sodium-benzophenone and MeCN
over P2O5. The chromatographic separations were achieved
on silica gel (0.060±0.200 nm, pore diameter ca. 4 nm)
available from ACROS. The 1H and 13C NMR spectra
were recorded on Brucker AC 200 and DPX 300 instru-
ments and carried out in CDCl3 and the MS spectra on a
HP 5890 gas chromatograph equipped with an HP 5970
mass selective detector.
2.1. Preparation of homoallyl ethoxycarbonylhydrazines
1
The goal of this work was to study the selenium-induced
cyclization of homoallylhydrazine derivatives: PhSeBr
treatment of the N0-but-3-en-1-yl N-ethoxycarbonylhydra-
zines 1, phenylhydrazines 2 and N,N-dimethylhydrazines
3 in CH3CN containing sodium carbonate, has led to the
formation of phenylselanylmethylpyrazolidine derivatives.
In all cases, a 5-exo-trig ring closure was observed. An
excess of PhSeBr has led to the oxidation of pyrazolidines
4 (R2ˆH) into 2-pyrazolines 5 and of pyrazolidines 4
(R2±H) into 1-pyrazolines 8. Phenylhydrazines 2 afforded
directly 1-phenyl-2-pyrazolines 10 and the dimethylhydra-
zines 3 the 1,1-dimethylpyrazolidinium bromides 11.
Pyrazolidines 4 (R2ˆH), 2-pyrazolines 5 (RˆCOOEt) and
10 (RˆPh) were deselenylated by the classical free-radical
method. The action of SO2Cl2 or Br2 on 2-pyrazolines 5 has
led to stable Se-dihalo adducts 15 (XˆCl) and 16 (XˆBr).
The dibromoselenurane 16b (R1ˆEt) was decomposed
giving a 51/15 mixture of bromomethyl-2-pyrazoline 17b
and pyrazole 18b. An unexpected p-halogenation of the
N-phenyl substituent was observed on heating the dihalo-
A solution of allylmagnesium chloride solution (2 M in
THF) (1.5 equiv., 15 mmol, 7.5 ml when R2ˆH (a±d))
was slowly added, under argon, to the corresponding ethoxy-
carbonylhydrazone (10 mmol) in THF (40 ml) at 2788C.
The reaction mixture was stirred overnight and quenched
with aqueous ammonium chloride (10%, 40 ml) at 08C and
extracted with ether (2£20 ml). The combined organic
phases were washed with brine (2£20 ml), dried over
anhydrous magnesium sulfate and evaporated under
reduced pressure. The hydrazine 1 was used without puri®-
cation for the cyclization step. 3.0 equiv. (30 mmol, 15 ml)
of allylmagnesium chloride were used for hydrazones
bearing R1 and R2±H.
2.1.1. 1-Ethoxycarbonyl-2-(1-phenylbut-3-en-1-yl)hydra-
zine 1a. Oil, 1H NMR, d: 7.24±7.34 (m, 5H, Ph), 6.1 (s, 1H,
NH), 5.67±5.90 (m, 1H, H3), 5.04±5.17 (m, 2H, H4), 4.70 (t,
1H, H1, Jˆ7.0 Hz), 4.20 (s, 1H, NH), 4.12 (q, 2H, H6,
Jˆ7.1 Hz), 2.49 (t, 2H, H2, Jˆ7.0 Hz), 1.23 (t, 3H, H7,
Jˆ7.1 Hz). 13C NMR, d: 157.1 (C5), 134.1 (C3), 128.0,

10264
M. Ternon et al. / Tetrahedron 57 (2001) 10259±10270
126.9, 126.6, 125.5 (Ph), 117.4 (C4), 63.0 (C1), 61.0 (C6),
43.3 (C2), 14.1 (C7).
(allylmagnesium chloride, 2 equiv.). They were used with-
out puri®cation for the following step.
2.2.1. 1-Phenyl-2-(1-phenylbut-3-en-1-yl)hydrazine 2a.20
Oil, H NMR, d: 7.31 (m, 7H, Ph), 6.68 (m, 3H, Ph), 5.71
2.1.2. 1-Ethoxycarbonyl-2-(hex-5-en-3-yl)hydrazine 1b.
Oil, H NMR, d: 6.25 (s, 1H, NH), 5.66±5.92 (m, 1H,
1
1
(m, 1H, H3), 4.8±5.05 (m, 3H, NH, H4), 3.89 (t, 1H, H1,
Jˆ6.7 Hz), 3.40 (s, 1H, NH), 2.48 (m, 2H, H2). 13C NMR, d:
149.8 (Ph), 135.6 (C3), 129.7, 129.5, 129.2, 129.1, 128.2,
122.9 (Ph), 117.9 (C4), 113.5 (Ph), 62.9 (C1), 39.2 (C2).
H5), 4.99±5.14 (m, 2H, H6), 4.11 (q, 2H, H8, Jˆ7.1 Hz),
3.4 (s, 1H, NH), 2.75±2.90 (m, 1H, H3), 1.90±2.25 (m,
2H, H4), 1.38 (quint, 2H, H2, Jˆ7.4 Hz), 1.22 (t, 3H, H9,
Jˆ7.1 Hz), 0.87 (t, 3H, H1, Jˆ7.4 Hz). 13C NMR, d: 157.4
(C7), 135.0 (C6), 117.0 (C5), 60.9 (C8), 59.6 (C3), 36.0 (C4),
24.3 (C2), 14.3 (C9), 9.3 (C1).
2.2.2. 2-(Hex-5-en-3-yl)-1-phenylhydrazine 2b. Oil, 1H
NMR, d: 7.15±7.23 (m, 2H, Ph), 6.87±6.89 (m, 2H, Ph),
6.75±6.79 (m,1H, Ph), 5.70±5.97 (m, 1H, H5), 5.05±5.19
(m, 2H, H6), 5.10 (s, 1H, NH), 3.15 (s, 1H, NH), 2.80 (quint,
1H, H3, Jˆ7.4 Hz), 2.18±2.28 (m, 2H, H4), 1.47 (quint, 2H,
H2, Jˆ7.4 Hz), 0.95 (t, 3H, H1, Jˆ7.4 Hz). 13C NMR, d:
149.6 (Ph), 135.3 (C5), 128.7, 118.3 (Ph), 117.0 (C6), 112.5
(Ph), 59.8 (C3), 36.3 (C4), 24.6 (C2), 9.8 (C1).
2.1.3. 1-Ethoxycarbonyl-2-(2-methylhex-5-en-3-yl)hydra-
zine 1c. Oil, H NMR, d: 6.2 (s, 1H, NH), 5.66±5.92 (m,
1
1H, H5), 4.99±5.14 (m, 2H, H6), 4.10 (q, 2H, H8, Jˆ7.1 Hz),
3.5 (s, 1H, NH), 2.69±2.80 (m, 1H, H3), 2.13±2.23 (m, 1H,
H2), 1.77±2.02 (m, 2H, H4), 1.24 (t, 3H, H9, Jˆ7.1 Hz), 0.88
(d, 6H, H1, Jˆ6.6 Hz). 13C NMR, d: 157.2 (C7), 135.8 (C6),
117.0 (C5), 63.2 (C3), 60.9 (C8), 32.6 (C4), 28.2 (C2), 18.4
(C1), 14.3 (C9).
2.2.3. 1-(2-Methylhex-5-en-3-yl)-2-phenylhydrazine 2c.
Oil, H NMR, d: 7.14±7.22 (m, 2H, Ph), 6.83±6.89 (m,
1
2H, Ph), 6.71±6.78 (m, 1H, Ph), 5.75±5.98 (m, 1H, H5),
5.09±5.19 (m, 2H, H6), 5.05 (s, 1H, NH), 3.30 (s, 1H,
NH), 2.67 (dt, 1H, H3), 1.82±2.35 (m, 3H, H2, H4), 0.94
(d, 6H, H1, Jˆ6.9 Hz). 13C NMR, d: 150.0 (Ph), 136.5
(C5), 129.0, 118.6 (Ph), 117.3 (C6), 112.6 (Ph), 64.2 (C3),
33.24 (C4), 28.7 (C2), 19.0 (C1).
2.1.4.
1-Ethoxycarbonyl-2-(1-phenylpent-4-en-2-yl)-
1
hydrazine 1d. Oil, H NMR, d: 7.16±7.28 (m, 5H, Ph),
6.1 (s, 1H, NH), 5.70±5.92 (m, 1H, H4), 5.06±5.14 (m,
2H, H5), 4.20 (s, 1H, NH), 4.10 (q, 2H, H7, Jˆ7.1 Hz),
3.17±3.28 (m, 1H, H2), 2.69 (t, 2H, H3), 2.15 (q, 2H, H1),
1.20 (t, 3H, H8, Jˆ7.1 Hz). 13C NMR, d: 157.1 (C6), 138.2
(Ph), 134.6 (C4), 128.9, 128.0, 125.9 (Ph), 117.4 (C5), 60.9
(C7), 59.4 (C2), 38.7 (C3), 36.9 (C1), 14.2 (C8).
2.2.4. 1-Phenyl-2-(1-phenylpent-4-en-2-yl)hydrazine 2d.
Oil, 1H NMR, d: 7.09±7.45 (m, 8H, Ph), 6.65±6.76 (m, 2H,
Ph), 5.70±5.95 (m, 1H, H4), 5.09±5.17 (m, 3H, H5, NH),
3.11 (quint, 2H, NH, H2, Jˆ6.3 Hz), 2.74 (d, 2H, H3, Jˆ
6.3 Hz), 2.25 (t, 2H, H1, Jˆ6.3 Hz). 13C NMR, d: 149.3,
138.9 (Ph), 135.2 (C4), 129.1, 128.7, 128.2, 126.1, 118.5
(Ph), 117.4 (C5), 112.4 (Ph), 60.1 (C2), 38.9 (C3), 36.9 (C1).
2.1.5.
1-Ethoxycarbonyl-2-(3-methylhex-5-en-3-yl)-
1
hydrazine 1e. Oil, H NMR, d: 5.90 (s, 1H, NH), 5.70±
5.89 (m, 1H, H5), 5.01±5.07 (m, 2H, H6), 4.10 (q, 2H, H9,
Jˆ7.1 Hz), 3.7 (s, 1H, NH), 2.08 (d, 2H, H4, Jˆ7.4 Hz),
1.35 (q, 2H, H2, Jˆ7.5 Hz), 1.21 (t, 3H, H10, Jˆ7.1 Hz),
0.95 (s, 3H, H7), 0.83 (t, 3H, H1, Jˆ7.5 Hz). 13C NMR, d:
157.6 (C8), 134.0 (C5), 117.3 (C6), 60.9 (C9), 58.6 (C3), 41.1
(C4), 29.2 (C2), 21.6 (C7), 14.2 (C10), 7.5 (C1).
2.2.5. 1,1-Dimethyl-2-(non-1-en-4-yl)hydrazine 3a. Oil,
1H NMR, d: 5.8±5.9 (m, 1H, H2), 5.02 (m, 2H, H1), 2.65
(quint, 1H, H4, Jˆ5.3 Hz), 2.33 (s, 6H, H10), 2.00±2.10 (m,
2H, H3), 1.8 (s, 1H, NH), 1.20±1.40 (m, 8H, H5, H6, H7, H8),
0.81 (t, 3H, H9, Jˆ6.3 Hz). 13C NMR, d: 136.0 (C2), 117.0
(C1), 56.3 (C4), 48.1 (C10), 37.7 (C3), 33.2 (C5), 32.1 (C6),
25.5 (C7), 22.6 (C8), 14.0 (C9).
2.1.6. 1-Ethoxycarbonyl-2-(3-phenylhex-5-en-3-yl)hydra-
zine 1f. Oil, 1H NMR, d: 7.17 (m, 5H, Ph), 5.5±5.8 (m, 2H,
NH, H5), 5.0 (m, 2H, H6), 4.03 (q, 2H, H8, Jˆ7.1 Hz), 3.6 (s,
1H, NH), 2.51 (dt, 2H, H4, Jˆ3.8, 6.6 Hz), 1.67 (q, 2H, H2,
Jˆ7.3 Hz), 1.12 (t, 3H, H9, Jˆ7.1 Hz), 0.67 (t, 3H, H1,
Jˆ7.3 Hz). 13C NMR, d: 157.0 (C7), 142.5 (Ph), 133.8
(C5), 128.1, 126.6, 126.2 (Ph), 117.6 (C6), 64.3 (C3), 61.1
(C8), 38.9 (C4), 28.5 (C2), 14.3 (C9), 7.5 (C1).
2.2.6. 2,2-Dimethyl-1-(3-ethylhex-5-en-3-yl)hydrazine 3b.
Oil, H NMR, d: 5.8±5.9 (m, 1H, H5), 4.95 (m, 2H, H6),
1
2.35 (s, 6H, H7), 2.07 (d, 2H, H4, Jˆ7.1 Hz), 1.8 (s, 1H,
NH), 1.28 (q, 4H, H2, Jˆ7.4 Hz), 0.74 (t, 6H, H1, Jˆ
7.4 Hz). 13C NMR, d: 135.1 (C5), 116.3 (C6), 60.2 (C3),
50.7 (C7), 39.1 (C4), 25.2 (C2), 7.4 (C1).
2.1.7. 1-Ethoxycarbonyl-2-(3-ethylhex-5-en-3-yl)hydra-
zine 1g. Oil, H NMR, d: 5.9 (s, 1H, NH), 5.71±5.91 (m,
1
1H, H5), 5.02±5.10 (m, 2H, H6), 4.11 (q, 2H, H8, Jˆ7.1 Hz),
3.4 (s, 1H, NH), 2.05 (dt, 2H, H4, Jˆ1.1, 7.3 Hz), 1.31 (q,
4H, H2, Jˆ7.3 Hz), 1.21 (t, 3H, H9, Jˆ7.1 Hz), 0.81 (t, 6H,
H1, Jˆ7.3 Hz). 13C NMR, d: 157.4 (C7), 133.8 (C5), 117.0
(C6), 60.7 (C8), 60.5 (C3), 38.1 (C4), 25.7 (C2), 14.1 (C9), 7.0
(C1).
2.2.7. 1-(1-Allylcyclohexyl)-2,2-dimethylhydrazine 3c.
Oil, H NMR, d: 5.8±5.9 (m, 1H, H3), 5.0 (m, 2H, H4),
2.36 (s, 6H, H8), 2.09 (d, 2H, H2, Jˆ7.1 Hz), 1.8 (s, 1H,
NH), 1.20±1.4 (m, 10H, H5, H6, H7). 13C NMR, d: 135.2
(C3), 117.0 (C4), 57.6 (C1), 51.0 (C8), 40.5 (C2), 34.2, 25.9,
22.3 (C2, C3, C7).
1
2.2. Preparation of homoallyl phenylhydrazines 2 and
dimethylhydrazines 3
2.3. Cyclization of the homoallyl ethoxycarbonyl-
hydrazines 1
The same method was used for phenylhydrazines 2 (allyl-
magnesium chloride, 3 equiv.) and of dimethylhydrazines 3
Method A: PhSeBr (0.708 g, 3 mmol) in anhydrous CH3CN
(20 ml) was added, at room temperature, to the homoallylic

M. Ternon et al. / Tetrahedron 57 (2001) 10259±10270
10265
ethoxycarbonylhydrazine 1 (2 mmol) dissolved in the same
solvent (10 ml) containing sodium carbonate (400 mg). The
mixture was stirred for 16 h and treated with a NaCl aq.
solution. After separation, the aqueous layer was extracted
with CH2Cl2 (2£10 ml). The concentration of the organic
layer has led to an oily residue chromatographied on silica
gel. PhSeSePh was ®rst separated by cyclohexane elution.
From hydrazines 1a±d (R2ˆH), 2-pyrazolines 5 were
separated (cyclohexane/ether: 80/20) then the pyrazolidines
4 (cyclohexane/ether: 60/40). From hydrazines 1e±g
(R2±H), the 1-pyrazolines 8 were ®rst eluted (cyclo-
hexane/ether: 90/10) and then the pyrazolidines 4 (cyclo-
hexane/ether: 60/40).
129.0, 126.77 (Ph), 66.0 (C3), 61.4 (C7), 58.9 (C5), 38.6 (C4),
32.8 (C9), 30.3 (C10), 20.6, 18.7 (C11), 14.5 (C8).
2.3.5. 1-Ethoxycarbonyl-3-isopropyl-5-(phenylselanyl-
methyl)-4,5-dihydro-1H-pyrazole 5c. (Method B) Oil,
1
yieldˆ70%, H NMR, d: 7.48±7.54 (m, 2H, Ph), 7.21±
7.27 (m, 3H, Ph), 4.39±4.52 (m, 1H, H5), 4.17 (q, 2H, H7,
Jˆ7.1 Hz), 3.45 (dd, 1H, H9, Jˆ12.6, 2.5 Hz), 2.61±3.02
0
(m, 4H, H10, H9 , H4), 1.25 (t, 3H, H8, Jˆ7.1 Hz), 1.09 (d,
6H, H11, Jˆ6.9 Hz). 13C NMR, d: 163.1 (C3), 153.1 (C6),
132.2, 129.0, 128.7, 126.9 (Ph), 61.7 (C7), 56.8 (C5), 37.5
(C4), 30.1 (C9), 29.5 (C10), 20.1, 19.7 (C11), 14.5 (C8). MS
(EI, 70 eV): 354 (M1z, 15), 183 (30), 69 (100). Anal. Calcd
for C16H22N2O2Se: C, 54.39;H, 6.28;N, 7.93;found: C,
54.15;H, 6.14;N, 7.82.
Method B: Using an excess of PhSeBr (3 equiv.), the
2-pyrazolines 5 and the 1-pyrazolines 8 were only formed.
2.3.6. 3-Benzyl-1-ethoxycarbonyl-5-(phenylselanylmethyl)-
pyrazolidine 4d. (Method A) Oil, yield ,10%, 1H NMR, d:
7.40 (m, 2H, Ph), 7.00±7.30 (m, 8H, Ph), 4.10±4.20 (m, 1H,
H5), 4.01 (q, 2H, H7, Jˆ7.1 Hz), 3.8 (s, 1H, NH), 3.17 (dd,
2.3.1. 1-Ethoxycarbonyl-3-phenyl-5-(phenylselanyl-
methyl)-4,5-dihydro-1H-pyrazole 5a. (Method B)
1
mpˆ438C, yieldˆ73%, H NMR, d: 7.62±7.66 (m, 2H,
0
Ph), 7.48±7.50 (m, 2H, Ph), 7.31±7.33 (m, 3H, Ph), 7.19±
7.21 (m, 3H, Ph), 4.58 (m, 1H, H5), 4.18 (q, 2H, H7, Jˆ
7.1 Hz), 3.50 (d, 1H, H9, Jˆ12.2 Hz), 3.33 (dd, 1H, H4,
Jˆ11.0, 17.6 Hz), 3.10 (dd, 1H, H4, Jˆ4.5, 17.6 Hz), 2.87
(t, 1H, H9, Jˆ9.8 Hz), 1.29 (t, 3H, H8, Jˆ7.1 Hz). 13C NMR,
d: 153.7 (C3), 132.2, 131.0, 130.0, 129.1, 128.5, 128.3,
127.0, 126.5 (Ph), 62.0 (C7), 57.5 (C5), 38.4 (C4), 30.2
(C9), 14.5 (C8). Anal. Calcd for C19H20N2O2Se: C, 58.92;
H, 5.20;N, 7.23;found: C, 58.94;H, 5.36;N, 7.32.
2H, H3, H9, Jˆ3.1, 12.5 Hz), 3.03 (dd, 2H, H9 , H10, Jˆ4.1,
0
13.0 Hz), 2.47 (dd, 1H, H10 , Jˆ8.7, 13.0 Hz), 2.17 (hept,
0
1H, H4, Jˆ5.6 Hz), 1.43 (m, 1H, H4 ), 1.13 (t, 3H, H8, Jˆ
7.1 Hz). 13C NMR, d: 155.8 (C6), 137.0, 132.0, 129.6,
128.9, 128.5, 128.1, 126.7, 125.4 (Ph), 61.5 (C7), 60.8
(C3), 60.1 (C5), 40.1 (C4), 37.2 (C10), 32.5 (C9), 14.4 (C8).
2.3.7. 3-Benzyl-1-ethoxycarbonyl-5-(phenylselanyl-
methyl)-4,5-dihydro-1H-pyrazole 5d. (Method B) Oil,
1
yieldˆ73%, H NMR, d: 7.41±7.48 (m, 2H, Ph), 7.16±
2.3.2. 1-Ethoxycarbonyl-3-ethyl-5-(phenylselanylmethyl)-
pyrazolidine 4b. (Method A) Oil, yield ,10%, 1H NMR, d:
7.5 (m, 2H, Ph), 7.2 (m, 3H, Ph), 4.25±4.40 (m, 1H, H5),
4.10 (q, 2H, H7, Jˆ7.1 Hz), 3.65 (s, 1H, NH), 2.90±3.38 (m,
7.33 (m, 8H, Ph), 4.36±4.48 (m, 1H, H5), 4.18 (q, 2H, H7,
Jˆ7.1 Hz), 3.67 (s, 2H, H10), 3.36 (dd, 1H, H9, Jˆ12.7,
0
0
2.6 Hz), 2.77±2.91 (m, 2H, H9 , H4), 2.52 (dd, 1H, H4 ,
Jˆ18.2, 5.0 Hz), 1.27 (t, 3H, H8, Jˆ7.1 Hz). 13C NMR, d:
156.9 (C3), 135.3, 132.0, 131.9, 128.8, 128.6, 128.4, 128.2,
126.6 (Ph), 61.5 (C7), 57.0 (C5), 39.7 (C4), 36.4 (C10), 30.1
(C9), 14.3 (C8). MS (CI, 200 eV): 403 (MH1, 100). Anal.
Calcd for C20H22N2O2Se: C, 59.85;H, 5.52;N, 6.98;found:
C, 60.25;H, 5.27;N, 6.98.
0
3H, H9, H3), 2.39±2.57 (m, 1H, H4), 1.66±1.88 (m, 1H, H4 ),
1.15±1.50 (m, 2H, H10), 1.21 (t, 3H, H8, Jˆ7.1 Hz), 0.94 (t,
3H, H11, Jˆ7.4 Hz). 13C NMR, d: 155.2 (C6), 131.4, 129.1,
128.4, 126.2 (Ph), 61.1 (C3), 60.9 (C7), 58.5 (C5), 40.2 (C4),
32.1 (C9), 24.1 (C10), 14.1 (C8), 10.4 (C11). MS (EI, 70 eV):
342 (M1z, 35), 170 (90), 99 (100).
2.3.8.
1-Ethoxycarbonyl-3-ethyl-3-methyl-5-(phenyl-
2.3.3. 1-Ethoxycarbonyl-3-ethyl-5-(phenylselanylmethyl)-
4,5-dihydro-1H-pyrazole 5b. (Method B) Oil, yieldˆ82%,
1H NMR, d: 7.44±7.51 (m, 2H, Ph), 7.15±7.25 (m, 3H, Ph),
4.35±4.51 (m, 1H, H5), 4.16 (q, 2H, H7, Jˆ7.1 Hz), 3.43
selanylmethyl)pyrazolidine 4e. (Method A) Oil, yieldˆ
1
49%, diastereoisomers mixture (1/1), H NMR, d: 7.45
(m, 2H, Ph), 7.25 (m, 3H, Ph), 4.40 (m, 1H, H5), 4.10 (q,
2H, H7, Jˆ7.0 Hz), 3.86 (s, 1H, NH), 3.22 (m, 2H, H9),
0
0
2.00±2.30 (m, 1H, H4), 1.35±1.60 (m, 3H, H4 , H10), 1.19
(dd, 1H, H9, Jˆ12.4, 2.6 Hz), 3.05±2.76 (m, 2H, H9 ,H4),
2.60±2.72 (dd, 1H, H4, Jˆ18.1, 4.9 Hz), 2.33 (q, 2H, H10,
Jˆ7.5 Hz), 1.24 (t, 3H, H8, Jˆ7.1 Hz), 1.08 (t, 3H, H11,
Jˆ7.5 Hz). 13C NMR, d: 159.7 (C3), 132.1, 129.0,
128.6, 126.9 (Ph), 61.7 (C7), 56.9 (C5), 40.2 (C4), 30.1
(C9), 23.4 (C10), 14.5 (C8), 10.8 (C11). MS (EI, 70 eV):
340 (M1z, 60), 169 (60), 157 (25), 97 (100). Anal. Calcd
for C15H20N2O2Se: C, 53.10;H, 5.94;N, 8.26;found: C,
52.88;H, 6.31;N, 8.18.
(t, 3H, H8, Jˆ7.0 Hz), 1.16 and 0.92 (2s, 3H, H12), 0.83, 0.81
(2t, 3H, H11, Jˆ7.4 Hz). 13C NMR, d: 131.7, 129.6, 128.8,
126.6 (Ph), 61.4 (C7), 59.0, 58.7 (C5), 45.1 (C3), 32.6, 30.9,
29.4 (C4, C9, C10), 21.9, 21.2 (C12), 14.4 (C8), 8.8, 8.6 (C11).
MS (EI, 70 eV): 356 (M1z, 100), 327 (70), 281 (70), 185
(100). Anal. Calcd for C16H24N2O2Se: C, 54.08;H, 6.81;N,
7.88;found: C, 53.75;H, 6.85;N, 8.22.
2.3.9. 3-Ethyl-3-methyl-5-(phenylselanylmethyl)-4,5-di-
hydro-3H-pyrazole 8e. (Method B) Oil, yieldˆ85%,
2.3.4. 1-Ethoxycarbonyl-3-isopropyl-5-(phenylselanyl-
1
1
diastereoisomers mixture (1/1), H NMR, d: 7.5 (m, 2H,
methyl)pyrazolidine 4c. (Method A) Oil, yield ,10%, H
NMR, d: 7.5 (m, 2H, Ph), 7.20 (m, 3H, Ph), 4.42 (m, 1H,
H5), 4.02 (q, 2H, H7, Jˆ7.1 Hz), 3.70 (s, 1H, NH), 3.28 (dd,
Ph), 7.2 (m, 3H, Ph), 4.56 (m, 1H, H5), 3.68 and 3.62 (dd,
0
1H, H6, Jˆ5.1, 12.3 Hz), 3.05 and 3.02 (dd, 1H, H6 , Jˆ8.5,
0
1H, H9, Jˆ2.9, 12.5 Hz), 3.05 (m, 1H, H9 ), 2.74 (m, 1H,
12.3 Hz), 1.59±1.87 (m, 3H, H7, H4), 1.44 and 1.12 (s, 3H,
0
H3), 2.33 (m, 1H, H4), 1.64 (oct, 1H, H10, Jˆ7.0 Hz), 1.45
H9), 1.00 (m, 1H, H4 ), 0.90 and 0.75 (t, 3H, H8, Jˆ7.5 Hz).
0
(m, 1H, H4 ), 1.16 (t, 3H, H8, Jˆ7.1 Hz), 0.96 and 0.86 (dd,
13C NMR, d: 132.7, 129.2, 129.0, 127.0 (Ph), 93.1, 92.6
(C3), 88.3, 87.0 (C5), 34.5, 34.1, 31.8, 30.9, 30.6, 30.0 (C4,
6H, H11, Jˆ7.0 Hz). 13C NMR, d: 155.8 (C6), 132.1, 123.6,

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M. Ternon et al. / Tetrahedron 57 (2001) 10259±10270
C6, C7), 25.0, 22.3 (C9), 8.6, 8.3 (C8). MS (CI, 200 eV): 283
(MH1, 100), 125 (20), 97 (20). Anal. Calcd for C13H18N2Se:
C, 55.52;H, 6.45;N, 9.96;found: C, 55.36;H, 6.74;N,
10.26.
was added, at room temperature, to the homoallylic phenyl-
hydrazine 2 (2 mmol) in the same solvent (10 ml) con-
taining sodium carbonate (400 mg). The mixture was
stirred for 16 h and treated with a NaCl aq. solution. After
separation, the aqueous layer was extracted with CH2Cl2
(2£10 ml). The work-up of the organic phase has led to an
oily residue chromatographed on silica gel (cyclohexane/
CH2Cl2: 80/20).
2.3.10. 1-Ethoxycarbonyl-3-ethyl-3-phenyl-5-(phenyl-
selanylmethyl)pyrazolidine 4f. (Method A) Oil, yieldˆ
1
72%, diastereoisomers mixture (2/1), H NMR, d: 7.50
(m, 2H, Ph), 7.25 (m, 8H, Ph), 3.8±4.2 (m, 4H, NH, H5,
H7), 3.20 (m, 2H, H9), 2.83 (dd, 1H, H4, Jˆ12.5, 7.2 Hz),
1.90 (dd, 1H, H4, Jˆ12.5, 9.1 Hz), 1.71 (q, 2H, H10, Jˆ
7.0 Hz), 1.15 (t, 3H, H8, Jˆ7.1 Hz), 0.73 (t, 3H, H11, Jˆ
7.0 Hz). 13C NMR, d: 141.5, 132.1, 129.0, 128.2, 128.0,
126.8, 126.5, 126.1 (Ph), 61.3 (C7), 58.8 (C5), 33.3 (C10),
31.8, 29.0 (C4, C9), 14.1 (C8), 9.2 (C11). Anal. Calcd for
C21H26N2O2Se: C, 60.43;H, 6.28;N, 6.71;found: C,
60.47;H, 6.03;N, 6.89.
2.4.1. 1,3-Diphenyl-5-(phenylselanylmethyl)-4,5-dihydro-
1
1H-pyrazole 10a. Oil, yieldˆ80%, H NMR, d: 7.57 (d,
2H, Ph), 7.40 (d, 2H, Ph), 7.00±7.30 (m, 9H, Ph), 6.64 (d,
2H, Ph), 4.27 (tt, 1H, H5, Jˆ3.2, 10.5 Hz), 3.36 (dd, 1H, H4,
0
Jˆ11.2, 17.6 Hz), 3.11±3.25 (m, 2H, H4 , H6), 2.68 (dd, 1H,
H6 , Jˆ10.5, 12.5 Hz). 13C NMR, d: 148.2 (C3), Ph, 59.3
0
(C5), 38.6 (C4), 29.8 (C6). MS (CI, 200 eV): 393 (MH1,
100), 237 (15). Anal. Calcd for C22H20N2Se: C, 67.52;H,
5.15;N, 7.16;found: C, 67.78;H, 5.21;N, 7.26.
2.3.11. 3-Ethyl-3-phenyl-5-(phenylselanylmethyl)-4,5-di-
hydro-3H-pyrazole 8f. (Method B) Oil, yieldˆ64%, 2/1
diastereoisomers mixture, major diastereoisomer: 1H
NMR, d: 7.10±7.50 (m, 10H, Ph), 4.57 (oct, 1H, H5, Jˆ
5.1 Hz), 3.60 (dd, 1H, H6, Jˆ5.1, 12.3 Hz), 2.81 (dd, 1H,
2.4.2. 3-Ethyl-1-phenyl-5-(phenylselanylmethyl)-4,5-di-
1
hydro-1H-pyrazole 10b. Oil, yieldˆ90%, H NMR, d:
7.53±7.59 (m, 2H, Ph), 7.13±7.31 (m, 5H, Ph), 6.64±6.86
(m, 3H, Ph), 4.25 (ddt, 1H, H5, Jˆ2.6, 4.6, 10.3 Hz), 3.29
(dd, 1H, H6, Jˆ2.6, 12.4 Hz), 3.05 (dd, 1H, H4, Jˆ10.3,
0
H6 , Jˆ9.0, 12.3 Hz), 2.06 (dd, 1H, H4, Jˆ8.2, 12.3 Hz),
0
0
0
1.74 (q, 2H, H7, Jˆ7.4 Hz), 1.44 (1H, H4 , Jˆ8.2,
17.5 Hz), 2.80±2.69 (m, 2H, H4 , H6 ), 2.38 (q, 2H, H7,
Jˆ7.6 Hz), 1.16 (t, 3H, H8, Jˆ7.6 Hz). 13C NMR, d:
153.8 (C3), 145.0, 133.7, 129.3, 129.2, 128.8, 127.6,
118.6, 113.0 (Ph), 59.4 (C5), 41.1 (C4), 30.6 (C6), 23.8
(C7), 11.3 (C8). MS (EI, 70 eV): 344 (M1z, 10), 173 (100).
Anal. Calcd for C18H20N2Se: C, 62.97;H, 5.87;N, 8.16;
found: C, 62.72;H, 6.13;N, 8.38.
12.8 Hz), 0.66 (t, 3H, H8, Jˆ7.4 Hz). 13C NMR, d: Ph,
98.7 (C3), 88.3 (C5), 35.4 (C4), 33.6 (C7), 30.0 (C6), 8.8
(C8). Minor diastereoisomer: H NMR, d: 7.10±7.50 (m,
1
10H, Ph), 4.36 (oct, 1H, H5, Jˆ5.1 Hz), 3.65 (dd, 1H, H6,
0
Jˆ5.1, 12.3 Hz), 3.06 (dd, 1H, H6 , Jˆ9.0, 12.3 Hz), 2.15
(dd, 1H, H4, Jˆ8.2, 12.3 Hz), 1.74 (q, 2H, H7, Jˆ7.4 Hz),
0
1.31 (1H, H4 , Jˆ8.2, 12.8 Hz), 0.80 (t, 3H, H8, Jˆ7.4 Hz).
13C NMR, d: Ph, 98.2 (C3), 87.8 (C5), 35.3 (C4), 34.6 (C7),
30.0 (C6), 9.1 (C8).
2.4.3.
3-Isopropyl-1-phenyl-5-(phenylselanylmethyl)-
1
4,5-dihydro-1H-pyrazole 10c. Oil, yieldˆ82%, H NMR,
d: 7.59±7.53 (m, 2H, Ph), 7.30±7.13 (m, 5H, Ph), 6.86±
6.72 (m, 3H, Ph), 4.27 (ddt, 1H, H5, Jˆ2.6, 4.5, 10.4 Hz),
3.28 (dd, 1H, H6, Jˆ2.6, 12.3 Hz), 3.04 (dd, 1H, H4, Jˆ10.4,
2.3.12. 1-Ethoxycarbonyl-3,3-diethyl-5-(phenylselanyl-
1
methyl)pyrazolidine 4g. (Method A) Oil, yieldˆ45%, H
0
0
NMR, d: 7.45 (m, 2H, Ph), 7.25 (m, 3H, Ph), 4.40 (m, 1H,
H5), 4.11 (q, 2H, H7, Jˆ7.0 Hz), 3.7 (s, 1H, NH), 3.22 (m,
17.3 Hz), 2.81±2.65 (m, 3H, H4 , H6 , H7), 1.15 (d, 6H, H8,
Jˆ6.9 Hz). 13C NMR, d: 157.2 (C3), 145.0, 133.8, 129.2,
129.1, 128.8, 127.6, 118.6, 113.0 (Ph), 59.4 (C5), 39.0 (C4),
30.4 (C6), 29.8 (C7), 20.4 (C8). MS (EI, 70 eV): 358 (M1z,
10), 187 (100). Anal. Calcd for C19H22N2Se: C, 63.86;H,
6.20;N, 7.84;found: C, 63.95;H, 6.32;N, 8.16.
0
2H, H9), 2.05±2.15 (m, 1H, H4), 1.25±1.80 (m, 5H, H4 ,
H10), 1.19 (t, 3H, H8, Jˆ7.0 Hz), 0.88 and 0.77 (2t, 6H,
H11, Jˆ7.4 Hz). 13C NMR, d: 131.8, 129.7, 128.9, 126.6
(Ph), 61.3 (C7), 58.7 (C5), 43.7 (C3), 32.7, 26.8 (C4, C9),
26.2 (C10), 14.6 (C8), 8.6, 7.8 (C11). MS (EI, 70 eV): 370
(M1z, 50), 341 (70), 295 (100), 199 (30). Anal. Calcd for
C17H26N2O2Se: C, 55.28;H, 7.09;N, 7.58;found: C, 55.47;
H, 7.02;N, 8.08.
2.4.4. 3-Benzyl-1-phenyl-5-(phenylselanylmethyl)-4,5-di-
1
hydro-1H-pyrazole 10d. Oil, yieldˆ70%, H NMR, d:
7.46±7.51 (m, 2H, Ph), 7.14±7.30 (m, 10H, Ph), 6.78±
6.87 (m, 3H, Ph), 4.26 (ddt, 1H, H5, Jˆ2.6, 4.5, 10.4 Hz),
3.70 (s, 2H, H7), 3.26 (dd, 1H, H6, Jˆ2.6, 12.3 Hz), 2.94 (dd,
2.3.13. 3,3-Diethyl-5-(phenylselanylmethyl)-4,5-dihydro-
3H-pyrazole 8g. (Method B) Oil, yieldˆ76%, 1H NMR, d:
7.5 (m, 2H, Ph), 7.2 (m, 3H, Ph), 4.51 (m, 1H, H5), 3.66 (dd,
1H, H4, Jˆ10.4, 17.3 Hz), 2.65±2.56 (m, 2H, H4 , H6 ). 13C
NMR, d: 150.6 (C3), 144.9, 137.2, 137.0, 134.1, 133.9,
129.4, 129.1, 128.9, 128.7, 127.7, 119.0, 113.2 (Ph), 59.1
(C5), 40.2 (C4), 36.5 (C7), 30.1 (C6). MS (EI, 70 eV): 406
(M1z, 10), 235 (50), 91 (100). Anal. Calcd for C23H22N2Se:
C, 68.14;H, 5.47;N, 6.91;found: C, 68.12;H, 5.28;N, 6.27.
0
0
0
1H, H6, Jˆ5.1, 12.1 Hz), 2.96 (dd, 1H, H6 , Jˆ8.9, 12.1 Hz),
0
1.83 (q, 2H, H7, Jˆ7.5 Hz), 1.62 (q, 2H, H7 , Jˆ7.5 Hz),
0
1.60 (hidden, 1H, H4), 1.03 (dd, 1H, H4 , Jˆ8.3, 13.0 Hz),
0.85 and 0.70 (t, 6H, H8, Jˆ7.5 Hz). 13C NMR, d: 132.1,
129.4, 129.0, 127.1 (Ph), 96.9 (C3), 88.3 (C5), 31.4 (C7),
30.4 (C6), 30.2 (C7), 29.1 (C4), 8.4, 8.1 (C8). MS (CI,
200 eV): 297 (MH1, 100). Anal. Calcd for C14H20N2Se:
C, 56.95;H, 6.83;N, 9.49;found: C, 57.26;H, 6.48;N, 9.56.
2.5. Cyclization of the homoallyl dimethylhydrazines 3
PhSeBr (0.708 g, 3 mmol) in anhydrous CH3CN (20 ml)
was added, at room temperature, to the homoallylic
dimethylhydrazine 3 (2 mmol) in the same solvent (10 ml)
containing sodium carbonate (400 mg). The mixture was
stirred for 16 h and treated with a NaCl aq. solution. The
2.4. Cyclization of the homoallyl phenylhydrazines 2
PhSeBr (0.708 g, 3 mmol) in anhydrous CH3CN (20 ml)

M. Ternon et al. / Tetrahedron 57 (2001) 10259±10270
10267
aqueous layer was extracted with CH2Cl2 (2£10 ml). The
white solid obtained, after concentration of the solvent, was
recrystallized in a 60/40 pentane/CH2Cl2 mixture.
21.7, 21.6 (C12), 20.6 (C9), 14.6 (C8), 8.9, 8.5 (C11). MS
(EI, 70 eV): 200 (M1z, 15), 185 (10), 171 (40), 125 (100).
Anal. Calcd for C10H20N2O2: C, 59.97;H, 10.06;N, 13.99;
found: C, 60.24;H, 10.18;N, 14.23.
2.5.1. 1,1-Dimethyl-3-pentyl-5-(phenylselanylmethyl)-
pyrazolidinium bromide 11a. Mpˆ1238C, yieldˆ55%,
2.6.2.
1-Ethoxycarbonyl-3-ethyl-5-methyl-3-phenyl-
1
two diastereoisomers are presents (1/1), H NMR, d: 7.50
1
pyrazolidine 12f. Oil, yieldˆ71%, H NMR, d: 7.2±7.7
(m, 5H, Ph), 4.50 (m, 1H, H5), 4.25 (q, 2H, H7, Jˆ
7.1 Hz), 3.5 (s, 1H, NH), 3.41 (dd, 1H, H4, Jˆ11.0,
(m, 2H, Ph), 7.31 (m, 3H, Ph), 4.19 and 4.00 (m, 1H, H5),
3.60 (m, 1H, H7), 3.56 and 3.52 (s, 3H, H6), 3.34 and 3.30 (s,
0
0
3H, H6 ), 3.13 and 2.98 (t, 1H, H7 , Jˆ11.3 Hz), 2.82 (quint,
1H, H3, Jˆ6.7 Hz), 2.50 (s, 1H, NH), 2.34±2.13 and 1.82±
1.60 (m, 2H, H4), 1.20±1.70 (m, 8H, H8, H9, H10, H11), 0.85
(t, 3H, H12, Jˆ7.5 Hz). 13C NMR, d: 133.3, 133.1, 129.5,
129.4, 128.2, 127.8, 127.5, 127.4 (Ph), 78.5, 77.3 (C5), 56.2,
53.6, 50.4, 46.7 (C6), 37.5 (C3), 36.2, 34.8 (C4), 33.4, 31.2,
26.2 (C8, C9, C10), 25.3, 24.5 (C7), 22.2 (C11), 13.7, 12.7
(C12). MS (FAB1): 341 (M12Br, 100). Anal. Calcd for
C17H29N2BrSe: C, 48.58;H, 6.95;N, 6.66;found: C,
48.63;H, 6.85;N, 6.74.
0
17.4 Hz), 2.78 (dd, 1H, H4 , Jˆ4.6, 17.4 Hz), 1.1±1.6 (m,
8H, H8, H9, H10), 0.82 (t, 3H, H11, Jˆ7.5 Hz). 13C NMR, d:
153.9 (C6), 131.6, 129.9, 128.5, 126.6 (Ph), 61.9 (C7), 53.9
(C5), 27.8 (C4), 26.9 (C10), 20.6 (C9), 14.7 (C8), 13.6 (C11).
2.6.3.
1-Ethoxycarbonyl-3,3-diethyl-5-methylpyrazo-
1
lidine 12g. Oil, yieldˆ71%, H NMR, d: 4.05±4.25 (m,
1H, H5), 4.13 (q, 2H, H7, Jˆ7.1 Hz), 3.25 (s, 1H, NH),
2.11 (dd, 1H, H4, Jˆ7.8, 12.0 Hz), 1.55±1.75 (m, 1H,
0
H4 ), 1.17±1.31 (m, 10H, H8, H9, H10), 0.87 and 0.80 (dt,
6H, H11, Jˆ7.5 Hz). 13C NMR, d: 147.8 (C6), 61.3 (C7), 54.7
(C5), 46.0 (C3), 27.1 (C4), 25.8 (C10), 20.6 (C9), 14.4 (C8),
8.3, 7.8 (C11). MS (EI, 70 eV): 214 (M1z, 5), 185 (50), 139
(100), 111 (70). Anal. Calcd for C11H22N2O2: C, 61.65;H,
10.35;N, 13.07;found: C, 61.67;H, 10.15;N, 13.25.
2.5.2. 3,3-Diethyl-1,1-dimethyl-5-(phenylselanylmethyl)-
1
pyrazolidinium bromide 11b. Mp 808C, yieldˆ55%, H
NMR, d: 7.55 (m, 2H, Ph), 7.26 (m, 3H, Ph), 3.72 (m,
1H, H5), 3.55 (d, 1H, H7, Jˆ11.5 Hz), 3.47, 3.44 (s, 6H,
0
H6), 2.89 (t, 1H, H7 , Jˆ11.5 Hz), 2.6 (s, 1H, NH), 2.44
(dd, 1H, H4, Jˆ6.2, 14.0 Hz), 1.86 (t, 1H, H4, Jˆ12.6 Hz),
1.40±1.70 (m, 4H, H8), 0.81 and 0.74 (t, 6H, H9, Jˆ7.3 Hz).
13C NMR, d: 133.0, 129.1, 127.7, 127.1 (Ph), 77.1 (C5), 63.9
(C3), 55.2, 50.0 (C6), 40.1 (C4), 31.6, 30.3 (C8), 23.2 (C7),
8.6, 7.9 (C9). MS (CI, 200 eV): 327 (MH12Br, 15). Anal.
Calcd for C16H27N2BrSe: C, 47.30;H, 6.70;N, 6.89;found:
C, 47.36;H, 6.99;N, 6.78.
2.6.4. 1-Ethoxycarbonyl-5-methyl-3-phenyl-4,5-dihydro-
1H-pyrazole 13a. Oil, yieldˆ76%, 1H NMR, d: 7.7 (m, 2H,
Ph), 7.2 (m, 3H, Ph), 4.46 (m, 1H, H5), 4.22 (q, 2H, H7,
Jˆ7.1 Hz), 2.36 (dd, 1H, H4, Jˆ11.0, 17.3 Hz), 2.75 (dd,
0
1H, H4 , Jˆ4.5, 17.3 Hz), 1.31 (d, 3H, H9, Jˆ6.3 Hz), 1.30
(t, 3H, H8, Jˆ7.1 Hz). 13C NMR, d: 153.5, 152.6 (C3, C6),
131.2, 129.6, 129.2, 126.3 (Ph), 61.6 (C7), 53.6 (C5), 40.6
(C4), 20.3 (C9), 14.4 (C8). MS (CI, 200 eV): 233 (MH1,
100). Anal. Calcd for C13H16N2O2: C, 67.22;H, 6.94;N,
12.06;found: C, 67.36;H, 7.16;N, 11.82.
2.5.3. 3,3-Cyclopentylene-1,1-dimethyl-5-(phenylselanyl-
methyl)pyrazolidinium bromide 11c. Mp.2008C, yieldˆ
62%, 1H NMR, d: 7.55 (m, 2H, Ph), 7.26 (m, 3H, Ph), 3.88
(m, 1H, H5), 3.62 (d, 1H, H7, Jˆ12.0 Hz), 3.51 and 3.43 (s,
2.6.5. 1-Ethoxycarbonyl-3-ethyl-5-methyl-4,5-dihydro-
1
0
6H, H6), 3.01 (t, 1H, H7 , Jˆ11.0 Hz), 2.9 (s, 1H, NH), 2.50
1H-pyrazole 13b. Oil, yieldˆ74%, H NMR, d: 4.15±
0
(d, 1H, H4, Jˆ9.0 Hz), 1.90 (t, 1H, H4 , Jˆ12.0 Hz), 1.40±
4.31 (m, 1H, H5), 4.16 (q, 2H, H7, Jˆ7.1 Hz), 2.94 (dd,
1.70 (m, 6H, cycle), 1.10±1.30 (m, 4H, cycle). 13C NMR, d:
133.5, 129.5, 128.2, 127.6 (Ph), 77.5 (C5), 61.8 (C3), 55.4,
50.5 (C6), 41.0 (C4), 39.2, 24.5, 23.7, 23.3 (C7, C8, C9, C10).
MS (FAB1): 339 (M12Br, 100). Anal. Calcd for
C17H27N2BrSe: C, 48.88;H, 6.51;N, 6.70;found: C,
49.01;H, 6.82;N, 6.81.
0
1H, H4, Jˆ10.6, 18.1 Hz), 2.22±2.34 (m, 3H, H4 , H10),
1.22 (t, 3H, H8, Jˆ7.1 Hz), 1.19 (d, 3H, H9, Jˆ6.3 Hz),
1.04 (t, 3H, H11, Jˆ7.6 Hz). 13C NMR, d: 159.4 (C3),
152.2 (C6), 61.0 (C7), 52.6 (C5), 41.5 (C4), 23.1 (C10), 19.8
(C9), 14.2 (C8), 10.4 (C11). MS (EI, 70 eV): 184 (M1z, 10),
169 (7), 125 (15), 97 (100), 69 (25). Anal. Calcd for
C9H16N2O2: C, 58.67;H, 8.75;N, 15.21;found: C, 58.42;
H, 9.01;N, 15.51.
2.6. General procedure for the radical reduction of 4, 5
or 10
2.6.6.
1-Ethoxycarbonyl-3-isopropyl-5-methyl-4,5-di-
hydro-1H-pyrazole 13c. Oil, yieldˆ65%, 1H NMR, d:
4.20±4.40 (m, 1H, H5), 4.21 (q, 2H, H7, Jˆ7.1 Hz), 2.95
(dd, 1H, H4, Jˆ10.6, 17.5 Hz), 2.74 (hept, 1H, H10, Jˆ
A solution of pyrazolidine 4 (or 2-pyrazoline 5 or 10),
Bu3SnH (0.437 g, 1.5 mmol) and AIBN (0.01 g) in toluene
(20 ml) was re¯uxed for 8 h. The solvent was then evapo-
rated and the residue puri®ed by chromatography on silica
gel (cyclohexane/ether: 60/40 for 12, cyclohexane/ether: 90/
10 for 13 and cyclohexane/CH2Cl2: 80/20 for 14)
0
6.9 Hz), 2.31 (dd, 1H, H4 , Jˆ4.3, 17.5 Hz), 1.27 (t, 3H,
H8, Jˆ7.1 Hz), 1.22 (d, 3H, H9, Jˆ6.9 Hz), 0.87 (dd, 6H,
H11, Jˆ6.9 Hz). 13C NMR, d: 163.1 (C3), 152.7 (C6), 61.6
(C7), 52.8 (C5), 39.3 (C4), 29.5 (C10), 20.1 (C11), 19.7 (C9),
14.5 (C8). MS (EI, 70 eV): 198 (M1z, 30), 183 (10), 139
(30), 111 (95), 97 (70), 69 (100). Anal. Calcd for
C10H18N2O2: C, 60.58;H, 9.15;N, 14.13;found: C, 60.38;
H, 9.26;N, 13.88.
2.6.1.
1-Ethoxycarbonyl-3-ethyl-3,5-dimethylpyrazo-
lidine 12e. Oil, yieldˆ67%, diastereoisomers mixture
1
(1/1), H NMR, d: 4.12 (q, 2H, H7, Jˆ7.1 Hz), 4.01±4.10
(m, 1H, H5), 3.50 (s, 1H, NH), 2.09 (m, 1H, H4), 1.45±1.69
0
(m, 1H, H4 ), 1.08±1.35 (m, 11H, H8, H9, H10, H12), 0.89 (dt,
3H, H11, Jˆ7.3 Hz). 13C NMR, d: 156.8 (C6), 61.1 (C7),
2.6.7. 3-Benzyl-1-ethoxycarbonyl-5-methyl-4,5-dihydro-
1H-pyrazole 13d. Oil, yieldˆ73%, H NMR, d: 7.15±
1
55.3, 55.0 (C5), 47.6, 47.0 (C3), 31.3 (C4), 29.1 (C10),

10268
M. Ternon et al. / Tetrahedron 57 (2001) 10259±10270
7.28 (m, 5H, Ph), 4.25±4.39 (m, 1H, H5), 4.27 (q, 2H, H7,
methyl)-4,5-dihydro-1H-pyrazole) dichloro-adduct 15b.
White solid, yieldˆ82%, 1H NMR, d: 7.9 (m, 2H, Ph), 7.45
(m, 3H, Ph), 5.32 (m, 1H, H5), 4.22±4.46 (m, 3H, H7, H9),
Jˆ7.1 Hz), 3.68 (d, 2H, H10), 2.86 (dd, 1H, H4, Jˆ10.8,
0
17.8 Hz), 2.19 (dd, 1H, H4 , Jˆ4.7, 17.8 Hz), 1.31 (t, 3H,
H8, Jˆ7.1 Hz), 1.15 (d, 3H, H9, Jˆ6.3 Hz). 13C NMR, d:
157.1 (C3), 152.6 (C6), 135.8, 128.6, 128.5, 126.8 (Ph), 61.5
(C7), 53.3 (C5), 41.5 (C4), 36.7 (C10), 20.6 (C9), 14.6 (C8).
MS (EI, 70 eV): 246 (M1z, 40), 231 (10), 159 (30), 91 (100).
Anal. Calcd for C14H18N2O2: C, 68.27;H, 7.37;N, 11.37;
found: C, 68.61;H, 7.15;N, 11.65.
4.11 (dd, 1H, H9 , Jˆ5.6, 10.5 Hz), 3.23 (dd, 1H, H4, Jˆ
0
0
10.5, 18.2 Hz), 2.9 (m, 1H, H4 ), 2.40 (q, 2H, H10, Jˆ
7.5 Hz), 1.33 (t, 3H, H8, Jˆ7.1 Hz), 1.11 (t, 3H, H11, Jˆ
7.5 Hz). 13C NMR, d: 160.0 (C3), 153.5 (C6), 141.0, 131.3,
129.6, 128.9 (Ph), 66.3 (C9), 62.6 (C7), 53.6 (C5), 40.6 (C4),
23.1 (C10), 14.5 (C8), 10.6 (C11).
2.6.8. 5-Methyl-1,3-diphenyl-4,5-dihydro-1H-pyrazole
2.7.2. (1-Ethoxycarbonyl-3-isopropyl-5-[(phenylselanyl-
methyl]-4,5-dihydro-1H-pyrazole) dichloro-adduct 15c.
1
14a. Solid, yieldˆ85%, H NMR, d: 7.0±7.7 (m, 10H,
1
Ph), 4.43 (m, 1H, H5), 3.38 (m, 1H, H4), 2.80 (m, 1H,
0
White solid, yieldˆ80%, H NMR, d: 7.9 (m, 2H, Ph), 7.5
H4 ), 1.23 (d, 3H, CH3, Jˆ6.2 Hz). 13C NMR, d: 148.1,
(m, 3H, Ph), 5.31 (m, 1H, H5), 4.2±4.5 (m, 3H, H7, H9), 4.12
0
136.8, 130.1, 129.0, 128.6, 126.3, 118.8, 114.1, 113.4 (C3,
Ph), 55.3 (C5), 40.4 (C4), 19.1 (C6). Anal. Calcd for
C16H16N2: C, 81.32;H, 6.82;N, 11.85, found: C, 80.99;
H, 7.01;N, 11.69.
(dd, 1H, H9 , Jˆ5.7, 10.3 Hz), 3.21 (m, 1H, H4, Jˆ5.7,
0
17.8 Hz), 2.9 (m, 1H, H4 ), 2.78 (hept, 1H, H10, Jˆ
6.9 Hz), 1.32 (t, 3H, H8, Jˆ7.1 Hz), 1.14 (d, 6H, H11, Jˆ
6.9 Hz). 13C NMR, d: 163.2 (C3), 153.5 (C6), 141.1, 131.5,
129.7, 120 (Ph), 66.2 (C9), 62.7 (C7), 53.5 (C5), 38.2 (C4),
29.5 (C10), 20.1, 19.7 (C11), 14.0 (C8).
2.6.9. 3-Ethyl-5-methyl-1-phenyl-4,5-dihydro-1H-pyra-
1
zole 14b. Oil, yieldˆ78%, H NMR, d: 7.20±7.32 (m,
2H, Ph), 7.03±7.07 (m, 2H, Ph), 6.75±6.81 (m, 1H, Ph),
4.12±4.28 (m, 1H, H5), 2.98±3.12 (m, 1H, H4), 2.35±2.50
2.8. Bromination of the 1-ethoxycarbonyl-2-pyrazoline
5b
0
(m, 3H, H4 , H7), 1.23 (d, 3H, H6, Jˆ6.2 Hz), 1.19 (t, 3H, H8,
Jˆ7.6 Hz). 13C NMR, d: 153.8 (C3), 145.5, 128.8, 118.2,
113.1 (Ph), 55.0 (C5), 42.7 (C4), 23.7 (C7), 18.9 (C6), 11.0
(C8). MS (EI, 70 eV): 188 (M1z, 40), 173 (100), 158 (10), 77
(45). Anal. Calcd for C12H16N2: C, 76.56;H, 8.57;N, 14.88;
found: C, 76.23;H, 8.78;N, 14.88.
A solution of Br2 in CCl4 (Cˆ100 g/l) (1.6 ml, 1 mmol) was
slowly added to the pyrazoline 5b in the same solvent
(10 ml). The solid dibromo-adduct 16b was formed imme-
diately. The mixture was re¯uxed for 30 min, treated with a
sodium thiosulfate aq. solution (10 ml) and then washed
with water (10 ml). The organic layer was dried over
magnesium sulfate and concentrated. The residue was puri-
®ed by silica gel chromatography. The pyrazole 18b was
®rst separated (cyclohexane/ether: 80/20). The bromo-
pyrazoline 17b was then eluted with the same mixture of
solvents.
2.6.10. 3-Isopropyl-5-methyl-1-phenyl-4,5-dihydro-1H-
1
pyrazole 14c. Oil, yieldˆ82%, H NMR, d: 7.18±7.27
(m, 2H, Ph), 7.01±7.06 (m, 2H, Ph), 6.72±6.80 (m, 1H,
Ph), 4.22 (hept, 1H, H5, Jˆ6.3 Hz), 3.04 (dd, 1H, H4, Jˆ
10.4, 16.9 Hz), 2.70 (hept, 1H, H7, Jˆ6.9 Hz), 2.43 (dd, 1H,
0
H4 , Jˆ5.1, 16.9 Hz), 1.20 (d, 3H, H6, Jˆ6.3 Hz), 1.16 (d,
6H, H8, Jˆ6.9 Hz). 13C NMR, d: 157.1 (C3), 145.5, 128.8,
128.1, 113.2 (Ph), 54.9 (C5), 40.5 (C4), 29.6 (C7), 20.2 (C8),
18.6 (C6). MS (EI, 70 eV): 202 (M1z, 30), 187 (50), 145
(100), 77 (50). Anal. Calcd for C13H18N2: C, 77.18;H,
8.97;N, 13.85;found: C, 76.85;H, 8.98;N, 14.12.
2.8.1. (1-Ethoxycarbonyl-3-ethyl-5-[(phenylselanylmethyl]-
4,5-dihydro-1H-pyrazole) dibromo adduct 16b. White
1
solid, H NMR, d: 8.0 (m, 2H, Ph), 7.5 (m, 3H, Ph), 5.39
0
(m, 1H, H5), 4.20±4.45 (m, 3H, H7, H9), 4.11 (m, 1H, H9 ),
0
3.25 (dd, 1H, H4, Jˆ11.2, 17.9 Hz), 2.9 (m, 1H, H4 ), 2.40
(q, 2H, H10, Jˆ7.5 Hz), 1.35 (t, 3H, H8, Jˆ7.1 Hz), 1.12 (t,
3H, H11, Jˆ7.5 Hz). 13C NMR, d: 151.1 (C3), 152.1 (C6),
138.0, 135.0, 129.9, 129.0 (Ph), 63.0 (C9), 56.9 (C7), 53.7
(C5), 41.1 (C4), 23.1 (C10), 14.5 (C8), 10.6 (C11).
2.6.11.
3-Benzyl-5-methyl-1-phenyl-4,5-dihydro-1H-
1
pyrazole 14d. Oil, yieldˆ70%, H NMR, d: 7.28±7.37
(m, 7H, Ph), 7.12±7.16 (m, 2H, Ph), 6.84±6.90 (m, 1H,
Ph), 4.26 (hept, 1H, H5, Jˆ5.5 Hz), 3.78 (s, 2H, H7), 2.97
0
(dd, 1H, H4, Jˆ10.6, 17.1 Hz), 2.35 (dd, 1H, H4 , Jˆ5.3,
2.8.2. 5-Bromomethyl-1-ethoxycarbonyl-3-ethyl-4,5-di-
17.1 Hz), 1.22 (d, 3H, H6, Jˆ6.2 Hz). 13C NMR, d: 151.0
(C3), 144.1, 136.8, 128.8, 128.6, 127.1, 126.5, 118.3, 113.2
(Ph), 55.2 (C5), 42.1 (C4), 36.8 (C7), 18.8 (C6). MS (EI,
70 eV): 250 (M1z, 60), 235 (30), 91 (100). Anal. Calcd for
C17H18N2: C, 81.56;H, 7.25;N, 11.19;found: C, 81.67;H,
7.42;N, 11.00.
1
hydro-1H-pyrazole 17b. Oil, yieldˆ51%, H NMR, d:
4.48 (m, 1H, H5), 4.22 (q, 2H, H7, Jˆ7.1 Hz), 3.59 (dd,
0
1H, H9, Jˆ2.8, 11.0 Hz), 3.5 (m, 1H, H9 ), 3.00 (dd, 1H,
0
H4, Jˆ11.0, 18.2 Hz), 2.73 (dd, 1H, H4 , Jˆ5.1, 18.2 Hz),
2.37 (q, 2H, H10, Jˆ7.5 Hz), 1.28 (t, 3H, H8, Jˆ7.1 Hz),
1.10 (t, 3H, H11, Jˆ7.5 Hz). 13C NMR, d: 159.7 (C3), 62.2
(C7), 57.5 (C5), 39.8 (C4), 26.9 (C9), 23.5 (C10), 14.7 (C8),
10.9 (C11). MS (CI, 200 eV): 263 (MH1, 100). Anal. Calcd
for C9H15N2BrO2: C, 41.08;H, 5.75;N, 10.65;found: C,
41.24;H, 5.71;N, 10.33.
2.7. Chloration of the 1-ethoxycarbonyl 2-pyrazolines 5
SO2Cl2 (134 mg, 1 mmol) in CCl4 (2 ml) was added drop-
wise to the pyrazoline 5 (1 mmol), at room temperature, in
the same solvent (10 ml). The mixture was stirred for
30 min. The product was ®ltred and washed with cyclo-
hexane.
2.8.3.
5-Bromomethyl-1-ethoxycarbonyl-3-ethyl-1H-
1
pyrazole 18b. Oil, yieldˆ15%, H NMR, d: 6.30 (s, 1H,
H4), 4.70 (s, 2H, H9), 4.47 (q, 2H, H7, Jˆ7.1 Hz), 2.60 (q,
2H, H10, Jˆ7.7 Hz), 1.40 (t, 3H, H8, Jˆ7.1 Hz), 1.17 (t, 3H,
H11, Jˆ7.7 Hz). 13C NMR, d: 158.0 (C3), 149.8 (C6), 143.7
2.7.1.
(1-Ethoxycarbonyl-3-ethyl-5-(phenylselanyl-

M. Ternon et al. / Tetrahedron 57 (2001) 10259±10270
10269
(C5), 111.2 (C4), 64.6 (C7), 22.1 (C9), 21.6 (C10), 14.3 (C8),
13.1 (C11). MS (EI, 70 eV): 262 (M1z, 10), 181 (30), 109
(100).
Ph), 106.3 (C4), 21.0 (C6). MS (CI, 200 eV): 391 (MH1,
100), 315 (30), 313 (30). Anal. Calcd for C16H12N2Br2: C,
49.01;H, 3.08;N, 7.14;found: C, 49.30;H, 3.16;N, 7.20.
2.10.2.
1-(4-Bromophenyl)-3-ethyl-5-[(phenylselanyl-
2.9. Chloration of the 1-phenyl-2-pyrazolines 10
methyl]-4,5-dihydro-1H-pyrazole 22b. Oil, yieldˆ54%,
1H NMR, d: 7.5 (m, 2H, Ph), 7.2±7.3 (m, 5H, Ph), 6.57
(d, 2H, Ph), 4.13 (m, 1H, H5), 3.15 (dd, 1H, H6, Jˆ2.0,
SO2Cl2 (134 mg, 1 mmol) in CCl4 (2 ml) was added drop-
wise to the pyrazoline 10 (1 mmol), at room temperature, in
the same solvent (10 ml). The mixture was re¯uxed for
30 min. and washed with aq. NaHCO3 solution (2£10 ml).
The organic layers were dried over magnesium sulfate
and concentrated. The residue was puri®ed by silica gel
chromatography (cyclohexane/CH2Cl2: 80/20).
0
12.3 Hz), 3.00 (dd, 1H, H6 , Jˆ10.7, 17.7 Hz), 2.70 (m,
2H, H4), 2.30 (q, 2H, H7, Jˆ7.6 Hz), 1.08 (t, 3H, H8, Jˆ
7.6 Hz). 13C NMR, d: 153.9 (C3), 143.1, 134.7, 134.3,
132.7, 132.2, 129.6, 127.2, 114.7 (Ph), 59.6 (C5), 41.6
(C4), 30.6 (C6), 24.1 (C7), 11.4 (C8). MS (EI, 70 eV): 422
(M1z, 10), 251 (100). Anal. Calcd for C18H19N2BrSe: C,
51.20;H, 4.54;N, 6.63;found: C, 51.36;H, 4.21;N, 6.62.
2.9.1.
1-(4-Chlorophenyl)-3-ethyl-5-(phenylselanyl-
methyl)-4,5-dihydro-1H-pyrazole 21b. Oil, yieldˆ86%,
1H NMR, d: 7.5±7.7 (m, 2H, Ph), 6.8±7.4 (m, 7H, Ph),
4.50 (m, 1H, H5), 3.55 (dd, 1H, H6, Jˆ3.5, 10.9 Hz), 3.43
2.10.3. 5-Bromomethyl-1-(4-bromophenyl)-3-ethyl-4,5-
dihydro-1H-pyrazole 23b. Oil, yield ,10%, H NMR, d:
1
7.25 (d, 2H, Ph, Jˆ9.0 Hz), 6.81 (d, 2H, Ph, Jˆ9.0 Hz), 4.36
0
(dd, 1H, H6 , Jˆ9.1, 10.9 Hz), 3.09 (dd, 1H, H4, Jˆ10.0,
(m, 1H, H5), 3.49 (dd, 1H, H6, Jˆ2.8, 10.3 Hz), 3.03±3.17
0
17.5 Hz), 2.87 (dd, 1H, H4 , Jˆ7.5, 17.5 Hz), 2.40 (q, 2H,
H7, Jˆ7.6 Hz), 1.21 (t, 3H, H8, Jˆ7.6 Hz). 13C NMR, d:
153.9 (C3), 144.2, 135.6, 131.0, 129.9, 129.4, 128.1, 127.2,
126.7, 125.0, 120.7 (Ph), 64.0 (C5), 44.7 (C4), 40.2 (C6),
23.6 (C7), 10.9 (C8). MS (CI, 200 eV): 379 (MH1, 100).
Anal. Calcd for C18H19ClN2Se: C, 57.23;H, 5.07;N, 7.42;
found: C, 57.51;H, 5.21;N, 7.23.
0
0
(m, 2H, H4, H6 ), 2.77 (dd, 1H, H4 , Jˆ4.6, 17.6 Hz), 2.33 (q,
2H, H7, Jˆ7.4 Hz), 1.12 (t, 3H, H8, Jˆ7.4 Hz). 13C NMR, d:
154.6 (C3), 143.7, 132.0, 114.3, 111.0 (Ph), 60.1 (C5), 40.9
(C6), 33.0 (C4), 23.6 (C7), 11.0 (C8). MS (EI, 70 eV): 346
(M1z, 30), 251 (100).
2.10.4. 5-Bromomethyl-1-(4-bromophenyl)-3-ethyl-1H-
pyrazole 24b. Oil, yield ,10%, H NMR, d: 7.53 (d, 2H,
Ph), 7.40 (d, 2H, Ph), 6.29 (s, 1H, H4), 4.36 (s, 2H, H6), 2.61
(q, 2H, H7, Jˆ7.5 Hz), 1.21 (t, 3H, H8, Jˆ7.5 Hz). MS (EI,
70 eV): 344 (M1z, 20), 263 (30), 184 (100).
1
2.9.2. 1-(4-Chlorophenyl)-3-isopropyl-5-(phenylselanyl-
methyl)-4,5-dihydro-1H-pyrazole 21c. Oil, yieldˆ81%,
1H NMR, d: 7.60 (m, 2H, Ph), 7.20 (m, 3H, Ph), 6.80±
7.00 (m, 4H, Ph), 4.43 (m, 1H, H5), 3.51 (dd, 1H, H6, Jˆ
0
3.4, 11.0 Hz), 3.40 (dd, 1H, H6 , Jˆ9.1, 11.0 Hz), 3.03 (dd,
2.10.5. 1-(4-Bromophenyl)-3-isopropyl-5-[(phenylselanyl-
methyl]-4,5-dihydro-1H-pyrazole 22c. Oil, yieldˆ59%,
1H NMR, d: 7.60 (m, 2H, Ph), 7.20 (m, 5H, Ph), 6.60 (m,
2H, Ph), 4.15 (m, 1H, H5), 3.12 (dd, 1H, H6, Jˆ2.6,
0
1H, H4, Jˆ10.1, 16.9 Hz), 2.83 (dd, 1H, H4 , Jˆ7.5,
16.9 Hz), 2.63 (hept, 1H, H7, Jˆ6.9 Hz), 1.16 (d, 6H, H8,
Jˆ6.9 Hz). 13C NMR, d: 159.6 (C3), 144.3, 136.0, 131.2,
130.1, 129.2, 128.2, 126.7, 124.3, 120.3 (Ph), 63.8 (C5), 44.5
(C4), 38.3 (C6), 30.4 (C7), 20.1 (C8). MS (CI, 200 eV): 393
(MH1, 100). Anal. Calcd for C19H21ClN2Se: C, 58.25;H,
5.40;N, 7.15;found: C, 58.63;H, 5.42;N, 7.26.
0
12.5 Hz), 2.98 (dd, 1H, H6 , Jˆ10.5, 17.3 Hz), 2.55±2.73
(m, 3H, H4, H7), 1.08 (d, 6H, H8, Jˆ6.9 Hz). 13C NMR, d:
157.8 (C3), 143.7, 133.9, 131.7, 129.2, 128.6, 127.7, 114.4,
110.3 (Ph), 59.1 (C5), 39.1 (C4), 30.1 (C6), 29.7 (C7), 20.3
(C8). MS (CI, 200 eV): 437 (MH1, 100). Anal. Calcd for
C19H21N2BrSe: C, 52.31;H, 4.85;N, 6.42;found: C, 52.61;
H, 5.02;N, 6.31.
2.10. Bromination of the 1-phenyl 2-pyrazolines 10
A solution of Br2 in CCl4 (Cˆ100 g/l) (1.6 ml, 1 mmol) was
slowly added to the pyrazoline in the same solvent (10 ml).
The dibromo adduct 20 precipitated immediatly. The
suspension was re¯uxed for 30 min, treated with a sodium
thiosulfate aq. solution (10 ml) and then washed with water
(10 ml). The organic layer was dried over magnesium
sulfate and concentrated. The residue was puri®ed by silica
gel chromatography. The pyrazole 24a and the phenyl-
selanylmethylpyrazoline 22c were separed by cyclo-
hexane/CH2Cl2: (80/20) elution. From 10b, the bromo-
pyrazoline 23b was ®rst separated (cyclohexane/CH2Cl2:
80/20). The phenylselanylmethylpyrazoline 22b and then
the bromomethylpyrazoline 24b were then eluted with the
same mixture of solvents.
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1
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