Regioselective 1,3-dipolar cycloaddition of nitrilimines to 2-methyl-2-vinyl oxirane

Article abstract of DOI:10.1016/j.tet.2011.03.017

1,3-Dipolar cycloaddition of in situ generated C,N-diaryl nitrilimines to 2-methyl-2-vinyl oxirane gives rise to the regioselective formation of novel 5-(2-methyloxiranyl)-4,5-dihydropyrazole derivatives in moderate to good yields. The structures and ster

Full text of DOI:10.1016/j.tet.2011.03.017

Tetrahedron 67 (2011) 3209e3215
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Regioselective 1,3-dipolar cycloaddition of nitrilimines to 2-methyl-2-vinyl
oxirane
*
€ €
Muhammet Yıldırım, Yas¸ ar Durust
_
Department of Chemistry, Abant Izzet Baysal University, TR-14280, Bolu, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
1,3-Dipolar cycloaddition of in situ generated C,N-diaryl nitrilimines to 2-methyl-2-vinyl oxirane gives
rise to the regioselective formation of novel 5-(2-methyloxiranyl)-4,5-dihydropyrazole derivatives in
moderate to good yields. The structures and stereochemistries of the new cycloadducts were confirmed
by spectroscopic/physical methods including X-ray diffraction data.
Received 26 November 2010
Received in revised form 16 February 2011
Accepted 7 March 2011
Available online 12 March 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Nitrilimine
Vinyl oxirane
Regioselective
Pyrazole
1. Introduction
derivatives, we have been interested in the present work to study
1,3-dipolar cycloaddition of diaryl substituted nitrilimines to 2-
1,3-Dipolar cycloaddition reactions occupy a significant place
due to their versatility in the construction of five-membered het-
erocylic systems.1 Most especially, nitrilimines have been utilized in
many cycloaddition reactions (generated in situ) and thus, pyrazole-
and pyrazoline-containing heterocycles have been intensively syn-
thesized for many years by using ethylenic, heterocyclic
dipolarophiles2e9 in the presence of different catalysts.10,11
methyl-2-vinyl oxirane.
2. Results and discussion
We performed the cycloaddition reaction of nitrilimines
obtained initially in situ from the treatment of C,N-diaryl substituted
a-chloro hydrazones with the excess triethylamine in dry
In general, 1,3-dipolar cycloaddition reactions of nitrilimines
with a dipolarophile having nonidentical terminalp-centers, such as
dichloromethane then with the addition of excess 2-methyl-2-vinyl
oxirane at room temperature. The progress of the reaction was fol-
lowed by TLC until all diarylnitrilimine has been consumed. The
overall reaction yielded a mixture of diastereomers (RR,RS) in
moderate to good yields (40e92%) with low diastereoselectivity
(Scheme 2). 5R,20R-6 and 5R,20S-7 diastereomershavebeen obtained
in the ratios between 62:38 and 36:64 (Table 1 and Scheme 1).
monosubstituted ethylenes can lead theoretically to the 5- and 4-
substituted 2-pyrazolines (regioisomers). Many examples reported
in the literature showed that the orientation observed for alkenes
substituted with electron-donor, conjugating, and moderate elec-
tron-acceptor substituents is the 5-substituted regioisomer.12,13 The
rationalization of such regiochemical results became evident in
terms of the frontier molecular orbital theory of Fukui.14e16
In addition, vinyl oxiranes are simple 2-alkenyl substituted ep-
oxides, which are attractive precursors for the construction of
functionalized four- and five-membered or larger rings by Pd-cat-
alyzed or intramolecular FriedeleCraft reactions.17e19
The only reported cycloaddition reaction of vinyl oxiranes in-
volved heterocumulenes; isocyanates and carbodiimides were used
as reagents.20
In this regard, to the best of our knowledge, since there is no
example of nitrilimine cycloaddition reactions to vinyl oxirane
Table 1
Diastereomeric ratios and yields of title compounds 6e7(aeh)
Compd R1
R2 Reaction Et3N
2M2VO Yield (%)a Diastereomeric
time (h) (equiv) (equiv)
ratio (5R,2R-6:5R,2S-7)
6ae7a
H
H
H
H
H
H
24
64
48
20
96
10
8
8
10
8
8
3
3
2
3
3
3
3
3
92
80
40
65
84
95
64
84
54:46 (i)b
62:38 (i)b
50:50 (s)
57:43 (i)b
53:47 (s)
58:42 (i)b
36:64 (s)
56:44 (i)b
6be7b CH3
6ce7c NO2
6de7d OCH3
6ee7e CF3
6fe7f Br
Cl 44
6ge7g NO2 Cl 64
6he7h CH3 CN 96
9
8
a
* Corresponding author. Tel.: þ90 374 2541243; fax: þ90 374 2534642; e-mail
Total yields of diastereomeric cycloadducts.
b
Assigned isomeric ratio using 1H NMR. i¼inseparable mixture s¼separated.
€ €
address: yasardurust@ibu.edu.tr (Y. Durust).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.017

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M. Yıldırım, Y. Durust / Tetrahedron 67 (2011) 3209e3215
3210
Scheme 1. Synthesis of 2-oxiranyl-4,5-dihydropyrazoles 6e7.
After several trials for the optimization of the reaction condi-
constants of the aliphatic protons in proton NMR, concurrent for-
mation of two diastereomers in nearly same amounts has been
observed and exact ratio of diastereomers has been determined by
comparing the integral values of aliphatic protons in crude reaction
mixture, especially, methyl protons (Figs. 1 and 2). Only di-
astereomers 6ce7c, 6ee7e, and 6ge7g could be separated from
each other by chromatography and they were obtained as single
diastereomers, the rest of cycloadducts yielded an inseparable di-
astereomeric mixture. Below, as a representative example, the
partial proton NMR spectra of 6e and 7e indicating the aliphatic and
methyl protons were shown (Fig. 1, Table 3). Among the aliphatic
protons, Hc is the most deshielded one due to its proximity to ni-
trogen and the oxiranyl moiety and it appeared at around 4 ppm in
both isomers as a doublet of doublets. The methylene protons of the
oxirane ring (Hd and He) in both isomers resonated relatively up-
field (2.60e2.80 ppm) with a J¼4.6 Hz and these values are in ac-
cord with the literature report (Fig. 3).21 The methylene protons of
the pyrazoline ring (Ha and Hb), exhibited a typical ABX spin sys-
tem with Hc as doublet of doublets with a J¼17.1 and 12.8 Hz. The
relationship between these protons can also clearly be seen in the
COSY spectrum. In addition, the HSQC spectra confirmed that the
connectivities of these protons to the carbons were also in accord
tions, the best yields and results were achieved by using 3 equiv of
2-methyl-2-vinyl oxirane and 8 equiv of triethylamine at room
temperature in CH2Cl2 (Table 2). Although excess amount of trie-
thylamine were used, it did not effect the formation of products in
higher yields during the course of reaction.
Table 2
Optimization of reaction conditions to yield compounds 6e7
Compd Reaction conditions
Et3N (equiv) 2M2VO (equiv) Yield (%)
6ae7a
6ae7a
6ce7c
6ce7c
6ce7c
CH3CN, reflux, 96 h
CH3CN, rt, 120 h
CH3CN, rt, 56 h
DCM, rt, 48 h
8
2
4
8
4
4
1.5
1.0
1.2
2.0
2.0
1.2
28
28
25
40
n.r
n.r
DCM, rt, 24 h
6he7h CH3CN, rt, catalyst, 24 h
The structural elucidation of the cycloadducts, namely, 2-
methyl-2-oxiranyl-substituted 4,5-dihydro-(1H)-pyrazoles (6 and
7) was performed by means of physical and spectroscopic methods,
principally 1H and 13C, COSY and HSQC NMR, IR spectra, and HRMS
measurements. Based on the chemical shifts and coupling
Fig. 1. Proton NMR splittings of the separated diastereomers 6e and 7e.

Fig. 2. Proton NMR splittings in the diastereomeric mixture of 6a and 7a.
Table 3
1H NMR chemical shifts and couplings of the cycloadducts 6 and 7
Compd R1
R2
Aromatic H
(ppm)
HaeHa0
(ppm) J (Hz)
HbeHb0
(ppm) J (Hz)
3.39e3.45, dd, 17.6, 5.8; 4.09e4.13, dd, 11.3, 5.1; 2.84, d, 4.7;
3.23e3.29, dd, 17.2, 6.6 4.04e4.09, dd, 12.7, 6.8 2.79, d, 4.7
3.27e3.33, dd, 17.6, 5.8; 3.97e4.01, dd, 11.9, 5.8; 2.74, d, 4.8;
3.11e3.17, dd, 17.2, 6.8 3.91e3.96, dd, 12.6, 6.8 2.68, d, 4.7
HceHc0
HdeHd0
HeeHe0
(ppm) J (Hz)
CH3
d
d
d
d
(ppm) J (Hz)
d
(ppm) J (Hz)
d
d
(ppm)
6ae7a
6be7b
H
H
H
7.76e6.87, 20H 3.54e3.61, dd, 17.4,
12.6; 3.62, d, 12.7
7.56e6.78, 18H 3.42e3.49, dd, 17.3,
12.5; 3.54, dd, 12.6
3.03, d, 4.6;
2.87, d, 4.8
2.93, d, 4.7;
2.76, d, 4.8
1.27, s
1.35, s
2.31, s;
1.17, s;
1.24, s
1.28, s
1.35, s
1.25, s;
1.18, s
1.16, s
1.25, s
1.16, s
1.20, s
1.16, s
1.21, s
2.30, s;
1.16, s
1.18, s
CH3
6c
7c
NO2
NO2
H
H
H
8.27e7.86 9H
8.20e6.91, 9H
7.61e6.77, 18H 3.41e3.53, td, 21.4, 12.5
3.55e3.62, dd, 17.7, 12.2; 3.42e3.48, dd, 17.7, 5.9; 4.20e4.24, dd, 12.2, 5.9; 2.87, d, 4.6
3.54e3.62, dd, 17.2, 13.0 3.21e3.27, dd, 17.2, 6.7 4.16e4.20, dd, 12.9, 6.6 2.74, d, 4.6
3.26e3.32, dd, 17.6, 5.9; 3.90e3.95, dd, 12.2, 6.5; 2.77, d, 4.7;
3.11e3.17, dd, 17.1, 6.8 3.75, s, (OCH3) 2.68, d, 4.7
3.44e3.50, dd, 17.6, 12.2; 3.31e3.35, dd, 17.6, 5.8; 4.05e4.09, dd, 12.2, 5.8; 2.75, d, 4.7
3.49e3.55, dd, 17.2, 12.8 3.15e3.20, dd, 17.2, 6.8 4.02e4.06, dd, 12.8, 6.7 2.69, d, 4.8
3.25e3.31, dd, 17.6, 5.7; 4.00e4.04, dd, 12.0, 5.6; 2.74, d, 3.2;
3.10e3.16, dd, 17.3, 6.7 3.90e3.95, dd, 12.7, 6.7 2.68, d, 4.6
3.33e3.38, dd, 18.0, 6.0; 4.12e4.16, dd, 12.0, 5.5; 2.75, d, 4.5
3.17e3.22, dd, 17.0, 6.5 4.03e4.07, dd, 10.5, 6.5 2.75, d, 5.0
3.30e3.35, dd, 17.7, 4.8; 4.10e4.13, dd, 11.8, 4.8; 2.74, d, 4.6;
3.15e3.20, dd, 17.4, 5.5 3.93e3.96, dd, 12.5, 5.7 2.70, d, 4.6
3.04, d, 4.4
2.80, d, 4.6
2.94, d, 4.7;
2.75, d, 4.7
2.94, d, 4.7
2.76, d, 4.7
2.88, d, 4.6;
2.73, d, 3.2
2.90, d, 5.0
2.70, d, 5.0
2.86, d, 4.6;
2.72, d, 4.6
6de7d CH3O
6e
7e
6fe7f
CF3
CF3
Br
H
H
Cl
7.75e6.83, 9H
7.73e6.82, 9H
7.50e7.02, 16H 3.42e3.54, td, 17.1, 12.7
6g
7g
NO2
NO2
Cl
Cl
8.18e7.07, 8H
8.16e7.21, 8H
3.48e3.54, dd, 17.5, 12.5
3.53e3.59, dd, 17.0, 13.0
6he7h CH3
CN 7.56e7.08, 16H 3.51e3.59, m

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M. Yıldırım, Y. Durust / Tetrahedron 67 (2011) 3209e3215
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resonated at around 140e150 ppm and oxirane methinic carbon at
around 53e57 ppm (Table 4). EI and APCI-TOF-MS measurements
gave the corresponding molecular ions. For some of the cyclo-
adducts 6 or 7, the base peaks were observed as either 1,3-di-
substituted dihydro-1H-pyrazole species 8, which is formed by the
cleavage of oxirane ring from the cycloadducts or corresponding
cyclopropene species 10 by the loss of nitrogen from pyrazole spe-
cies formed and occasionally, base peaks were observed as saturated
2-methyl oxirane species 9 by loss of nitrilimine species (Scheme 2).
The diastereoselectivity of the reaction and configurations of the
stereogenic centers of the cycloadducts 6c, 7c, and 7g were estab-
lished by single crystal X-ray diffraction (Fig. 4) and 2D-NMR
spectra. Thus, nitrilimine cycloaddition to 2-methyl-2-vinyl oxirane
are completely regioselective but yielded R,R-diastereomers as
slightly major product among the two diastereomers formed by
rotation of oxirane ring around single bond and it is obviously
found that the diastereoselectivity of the reaction is low when the
ratio of the diastereoisomers were compared (Table 1).
Fig. 3. Proton chemical shifts and couplings of 6c.
with the assigned structures. Thus, oxiranyl methylene protons
(2.69 and 2.77 ppm) coincide with the carbon at 52.5 ppm. Pyr-
azoline ring methylene protons (Ha and Hb; 3.20 and 3.55 ppm)
correlates with the carbon at 37.0 ppm.
In addition to the synthesis of partially unsaturated cyclo-
adducts, we have attempted to obtain fully aromatized pyrazoles
for
a deeper insight of the structures by conducting de-
The IR spectra of title compounds 6e7(aeh) showed the C]N
absorption bands around at 1593e1605 cmꢀ1 and CeOeC absorp-
hydrogenation reactions for the bridge protons by means of oxi-
dizing agents, such as DDQ, chloranil, iodine pentoxide, in different
reaction conditions according to the previously reported
tion bands of oxirane rings around at 1100e1180 cmꢀ1 13C NMR
.
spectra of all diastereomers showed that the C]N, iminic carbon
Table 4
13C NMR chemical shifts of the cycloadducts 6 and 7
Compd
R1
R2
d (ppm)
C1
C4
C5
C10
C14
C9
C8
C15
C13
C3
C6
C7
C2
C18
(C16)
(C11)
(C12)
(C17)
6a
7a
6b
7b
6c
7c
6d
7d
6e
7e
6f
H
H
H
H
H
H
H
H
H
H
150.0,
148.3,
156.0,
155.7,
143.9,
143.2,
151.1,
150.0,
146.1,
145.1,
147.7,
146.6,
147.3,
147.2,
150.9,
137.4,
132.8,
145.9,
145.7,
140.6,
140.3,
132.8,
129.5,
135.7,
135.8,
143.6,
143.2,
142.5,
142.6,
133.5,
147.3,
145.7,
150.0,
148.5,
135.3,
135.0,
146.0,
142.3,
144.5,
144.7,
143.9,
143.8,
138.2,
138.3,
147.7,
129.5,
129.5,
147.5,
146.3,
142.0,
140.6,
161.0,
160.6,
129.2,
129.2,
124.9,
124.9,
145.7,
144.6,
139.9,
129.2,
129.1,
129.7,
129.6,
126.1,
125.6,
142.1,
139.9,
125.7,
125.7,
129.5,
129.4,
129.2,
129.2,
129.5,
129.0,
128.9,
129.5,
129.5,
120.8,
120.4,
113.9,
113.7,
125.5,
125.5,
132.2,
132.2,
124.1,
124.0,
128.9,
126.2,
126.1,
126.2,
126.1,
122.4,
122.2,
129.3,
128.5,
125.5,
125.5,
127.7,
127.7,
126.0,
125.9,
126.2,
119.9,
119.8,
119.8,
119.7,
117.5,
117.2,
119.7,
119.5,
120.1,
120.0,
127.6,
127.4,
115.1,
115.0,
100.8,
114.0,
113.8,
114.0,
113.7,
110.8,
110.2,
114.5,
114.4,
113.8,
113.6,
115.2,
115.0,
110.5,
110.2,
113.2,
65.8,
64.7,
65.8,
64.7,
62.3,
62.2,
65.7,
64.7,
64.6,
65.6,
66.2,
64.7,
64.6,
66.1,
65.2,
59.5,
58.6,
59.5,
58.6,
54.7,
56.2,
53.4,
52.9,
58.0,
58.9,
59.3,
58.3,
57.7,
58.8,
58.8,
56.7,
52.8,
56.7,
52.8,
53.0,
48.8,
50.0,
48.6,
56.4,
52.4,
56.1,
52.6,
55.9,
52.2,
55.0,
37.8,
37.6,
37.9,
37.7,
33.4,
34.2,
38.0,
34.7,
36.9,
37.0,
37.8,
37.6,
36.8,
37.0,
37.9,
16.6
17.1
16.6,
17.1,
12.9
13.1
16.7,
17.2,
16.1,
16.7,
16.7
16.8
16.3
16.4
15.8,
CH3
CH3
NO2
NO2
CH3O
CH3O
CF3
CF3
Br
21.8(CH3)
21.7(CH3)
55.8 (OCH3)
56.7 (OCH3)
125.4(CF3)
125.5(CF3)
H
H
Cl
Cl
Cl
Cl
CN
7f
Br
6g
7g
6h
NO2
NO2
CH3
120.3 (C^N),
21.4 (CH3)
7h
CH3
CN
149.8,
133.4,
147.6,
139.7,
129.4,
128.7,
126.1,
100.7,
113.0,
62.9,
57.7,
51.8,
37.6,
16.5,
120.2 (C^N),
21.1 (CH3)

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X-ray Diffraction measurements were run on EnrafeNonius CAD-4
Diffractometer. ChromatotronÔ Centrifugal Thin-Layer Chromato-
graph System were used for isolation of final products. Melting
points were determined on a MELTEMP apparatus and uncorrected.
TLC was done using precoated plates with fluorescent indicator
(Merck 5735). The stain solutions of permanganate, phosphomo-
lybdic acid, and iodine were used for visualization of the TLC spots.
4.2. Synthesis of (R)-5-((R)-2-methyloxiran-2-yl)-1,3-disubsti-
tuted-4,5-dihydro-1H-pyrazoles or (R)-5-((S)-2-methyloxiran-
2-yl)-1,3-disubstituted-4,5-dihydro-1H-pyrazoles (6e7).
General procedure.
Scheme 2. EI mass spectral fragmentation of cycloadducts 6e7.
The corresponding hydrazonyl chloride 3 (0.5 mmol, 1.0 equiv)
and Et3N (2.0 mmol, 8 equiv) were dissolved in dry dichloro-
Fig. 4. X-ray ORTEP views of cycloadducts 6c and 7c.
methods22e24 but all these experiments were unsuccessful and no
aromatized cycloadducts could be obtained.
methane (20 mL) and stirred for 30 min. Then, isoprene monoxide
5 (1.5 mmol, 3.0 equiv) was added dropwise into the mixture and
reaction mixture was stirred at room temperature under N2 at-
mosphere. The progress of the reaction was monitored by TLC
(20e96 h). After the reaction is complete, the reaction was con-
centrated and the reaction mixture was mixed and stirred with
water (30 mL) to dissolve all the Et3N$HCl salt and extracted by
DCM (2ꢁ20 mL), dried over MgSO4, and solvent was removed. Fi-
nally, the cycloadducts 6e7 were column chromatographed on
silica gel (EtOAcehexane) as either single isomer or a mixture of
isomers.
3. Conclusions
From the above results we demonstrated the regioselective for-
mation of 5-oxiranyl substituted pyrazoles from nitrilimines and 2-
methyl-2-vinyl oxirane (isoprene monoxide). No 4-oxiranyl
substituted pyrazole cycloadducts were detected in the crude reaction
mixture. In some cases, the diastereomers could not be separated. The
structures were assigned by NMR and X-ray data. In conclusion, the
present protocol introduces the first example of regio- and diaster-
eoselective 1,3-dipolar cycloaddition of nitrilimines to 2-methyl-2-
vinyl oxirane at room temperature and with simple purification.
4.2.1. (R)-5-((R)-2-Methyloxiran-2-yl)-1,3-diphenyl-4,5-dihydro-1H-
pyrazole (6a) and (R)-5-((S)-2-methyloxiran-2-yl)-1,3-diphenyl-4,5-
dihydro-1H-pyrazole (7a). Two inseparable diastereomers. Compounds
6ae7a: Orange oily solid (110 mg, 92%). Melting range: 82e87 ꢂC. Rf:
4. Experimental section
4.1. General
0.55e0.45 (ethyl acetateen-hexane; 1:2). IR (KBr):
n
¼3057, 2983
(CeH), 2926, 1600 (C]N), 1552, 1500, 1394, 1323, 1124, 883,
758,750 cmꢀ1. TOF-MS EIþ: (m/z, %)¼278 (15) [M]þ, 221 (50), 176
(20), 105 (90), 85 (100). HRMS calculated for C18H18N2O 278.1419;
found 278.1417.
1H and 13C NMR spectra were recorded on BRUKER and VARIAN
spectrometers (400 and 500 MHz for proton and 100, 125 MHz for
carbon) and all chemical shifts are reported in parts per million
downfield from TMS. IR spectra were recorded on an SHIMADZU
FTIR-8400S instrument (KBr pellet or NaCl discs). MALDI-Mass
spectra were run on Bruker FTMS 4.7T BioAPEX II instrument and
also high resolution mass spectra of the compounds were measured
on a Bruker FTMS 4.7T BioAPEX II mass spectrometer. Single crystal
4.2.2. (R)-5-((R)-2-Methyloxiran-2-yl)-1-phenyl-3-p-tolyl-4,5-dihy-
dro-1H-pyrazole (6b) and (R)-5-((S)-2-methyloxiran-2-yl)-1-
phenyl-3-p-tolyl-4,5-dihydro-1H-pyrazole (7b). Two inseparable
diastereomers. Compounds 6be7b: White needles (117 mg, 80%).
Melting range: 92e98 ꢂC. Rf: 0.50e0.45 (ethyl acetateen-hexane;

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1:4). IR (KBr):
n
¼3036, 2922 (CeH), 2852, 1597 (C]N), 1500, 1390,
(m/z, %)¼347 (100) [MH]þ, 348 (25) [MH]þ. HRMS calculated for
1325, 1124, 815, 748 cmꢀ1. TOF-MS EIþ: (m/z, %)¼292 (30) [M]þ, 272
(15), 235 (100), 77 (20). HRMS calculated for C19H20N2O3 292.1576;
found 292.1578.
C19H18N2OF3 347.1371; found 347.1371.
4.2.6. (R)-3-(4-Bromophenyl)-1-(4-chlorophenyl)-5-((R)-2-methyl-
oxiran-2-yl)-4,5-dihydro-1H-pyrazole (6f) and (R)-3-(4-bromo-
phenyl)-1-(4-chlorophenyl)-5-((S)-2-methyloxiran-2-yl)-4,5-dihy-
dro-1H-pyrazole (7f). Two inseparable diastereomers. Compounds
6fe7f: White needles (108 mg, 95%). Melting range: 126e128 ꢂC. Rf:
4.2.3. (R)-5-((R)-2-Methyloxiran-2-yl)-3-(4-nitrophenyl)-1-phenyl-
4,5-dihydro-1H-pyrazole (6c) and (R)-5-((S)-2-methyloxiran-2-yl)
-3-(4-nitrophenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (7c). Two sep-
arated diastereomers. Compound 6c: Light orange needles (from
diisopropylphenylethereacetone) (30 mg, 20%). Mp 155e157 ꢂC. Rf:
0.40e0.30 (ethyl acetateen-hexane; 1:2). IR (KBr):
n
¼3049, 2922
(CeH), 2850, 1597 (C]N), 1490, 1386, 1093, 1006, 821 cmꢀ1. TOF-
MS APþ: (m/z, %)¼391 (80) [M]þ, 393 (100) [M]þþ2. HRMS calcu-
lated for C18H17N2OClBr 391.0213; found 391.0216.
0.75 (ethyl acetateen-hexane; 1:2). IR (KBr):
n
¼3047, 2924 (CeH),
2850, 1593 (C]N), 1552, 1500, 1340, 1107, 846, 752 cmꢀ1. TOF-MS
EIþ: (m/z, %)¼323 (35) [M]þ, 266 (90), 235 (95), 83 (100). HRMS
calculated for C18H17N3O3 323.1270; found 323.1276. Selected
4.2.7. (R)-1-(4-Chlorophenyl)-5-((R)-2-methyloxiran-2-yl)-3-(4-ni-
trophenyl)-4,5-dihydro-1H-pyrazole (6g) and (R)-1-(4-chloro-
phenyl)-5-((S)-2-methyloxiran-2-yl)-3-(4-nitrophenyl)-4,5-dihydro-
1H-pyrazole (7g). Two separated diastereomers. Compound 6g: Light
orange needles (40 mg, 24%). Mp 195e197 ꢂC. Rf: 0.60 (ethyl
crystallographic data: C18H17N3O3 F(000)¼680, Mr¼323.35,
Dx¼1.392 Mg mꢀ3. Monoclinic, P21/c Cu K
a
radiation,
l
¼1.54178 A.
ꢀ
Hall symbol: ꢀP 2 ybc. Cellꢂparameters from 3237 reflections
¼0.79 mmꢀ1
,
ꢀ
ꢀ
a¼17.0933 (9) A,
q
¼5.1e67.6 , b¼9.9259 (5) A,
m
c¼9.3363 (4) A, T¼90 K,
b
¼103.091 (3)ꢂ. Plate, Orange V¼1542.89
acetateen-hexane; 1:2). IR (KBr):
n
¼3109, 3039, 2912 (CeH), 2848,
ꢀ
3
(13) A , 0.24ꢁ0.21ꢁ0.05 mm, Z¼4. Data collection Bruker APEX-II
1593 (C]N), 1496, 1342, 1109, 819, 752 cmꢀ1. TOF-MS EIþ: (m/z,
%)¼357 (25) [M]þ, 327 (30), 300 (60), 269 (100). HRMS calculated
for C18H16N3O3Cl 357.0880; found 357.0876.
ꢀ
CCD diffractometer 8539 independent reflections. Radiation
source: fine-focus sealed tube 6947 reflections with I>2s(I)
graphite Rint¼0.0000
4
and
u
scans qmax¼69.3ꢂ, qmin¼5.1ꢂ. Ab-
Compound 7g: Orange-red needles (60 mg, 35%). Mp
sorption correction: Multi-scan SADABS (Sheldrick, 2002)
h¼ꢀ20/20Tmin¼0.832, Tmax¼0.961, k¼ꢀ11/118,539 measured
reflections l¼ꢀ8/10.
189e191 ꢂC. Rf: 0.45 (ethyl acetateen-hexane; 1:2). IR (KBr):
n
¼3064, 2924 (CeH), 2856,1593 (C]N),1491,1338,1323,1141,1097,
848, 821, 748 cmꢀ1. TOF-MS EIþ: (m/z, %)¼357 (25) [M]þ, 327 (40),
300 (60), 270 (100). HRMS calculated for C18H16N3O3Cl 357.0880;
found 357.0877.
Compound 7c: Dark orange needles (from diisopropylphenyle-
thereacetone) (25 mg, 20%). Mp 152e154 ꢂC. Rf: 0.62 (ethyl
acetateen-hexane; 1:2). IR (KBr):
n
¼3059, 2926 (CeH), 2854, 1593
(C]N),1552,1502,1340,1107, 846, 752 cmꢀ1. TOF-MS EIþ: (m/z, %)¼
323 (5) [M]þ, 289 (20), 273 (40), 235 (100), 83 (100). HRMS calcu-
lated for C18H17N3O3 323.1270; found 323.1269. Selected crystallo-
4.2.8. 4-((R)-5-((R)-2-Methyloxiran-2-yl)-3-p-tolyl-4,5-dihydro-1H-
pyrazol-1-yl) benzonitrile (6h) and 4-((R)-5-((S)-2-methyloxiran-2-
yl)-3-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)benzonitrile (7h). Two
inseparable diastereomers. Brown powder (75 mg, 65%). Melting
range: 137e145 ꢂC. Rf: 0.22e0.11 (ethyl acetateen-hexane; 1:2). IR
graphic data: C18H17N3O3 Z¼2, Mr¼323.35, F(000)¼340. Triclinic, P1
Dx¼1.391 Mg mꢀ3. Hall symbol: ꢀP 1 Cu K
a
radiation,
l
¼1.54178 A,
ꢀ
ꢀ
a¼6.2053 (7) A. Cꢂell parameters from 891 reflections b¼10.8579
(KBr):
n¼3049, 2922 (CeH), 2860, 2214 (C^N), 1605 (C]N), 1510,
ꢀ
ꢀ
(12) A,
q
¼3.7e56.9 , c¼11.8305 (14) A,
m
¼0.79 mmꢀ1
, a
g
¼98.431 (9)ꢂ,
1398, 1332, 1174, 827 cmꢀ1. TOF-MS APþ: (m/z, %)¼318 (100) [M]þ,
359 (30) [M]þþK. HRMS calculated for C20H20N3O 318.1606; found
318.1620.
T¼90 K,
b
¼91.549 (9)ꢂ. Fragment, Orange
¼101.223 (9)ꢂ
3
ꢀ
0.13ꢁ0.10ꢁ0.04 mm, V¼772.14 (15) A . Data collection Bruker APEX-
II CCD diffractometer 2186 independent reflections. Radiation
source: fine-focus sealed tube 1086 reflections with I>2s(I) graphite
5. Supplementary data
Rint¼0.118
4
and
u
scans qmax¼59.1ꢂ, qmin¼3.7ꢂ. Absorption correc-
tion: Multi-scan SADABS (Sheldrick, 2002) h¼ꢀ5/6 Tmin¼0.904,
Tmax¼0.969, k¼ꢀ9/126,710 measured reflections l¼ꢀ12/13.
Full crystallographic data for 7c and 6c have been deposited
with the CCDC reference numbers 798327, 797328, respectively,
and can be obtained free of charge via http://www.ccdc.cam.ac.uk/
data_request/cif.
4.2.4. (R)-3-(4-Methoxyphenyl)-5-((R)-2-methyloxiran-2-yl)-1-phe-
nyl-4,5-dihydro-1H-pyrazole (6d) and (R)-3-(4-methoxyphenyl)-5-
((S)-2-methyloxiran-2-yl)-1-phenyl-4,5-dihydro-1H-pyrazole (7d).
As a mixture of two inseparable diastereomers. Compounds6de7d:
Brown oil (75 mg, 65%). Rf: 0.75e0.65 (ethyl acetateen-hexane;
Acknowledgements
_
Abant Izzet Baysal University, Directorate of Research Projects
1:2). IR (KBr):
n
¼3049, 2931 (CeH), 2837, 1597 (C]N), 1500, 1390,
Commission (BAP grant no. 2007.03.03.260) and TUBITAK (Turkish
Scientific and Technological Research Council) (grant no. 106T645)
are gratefully acknowledged for financial support.
The authors also thank to Professor D.W. Knight (School of
Chemistry, Cardiff University, U.K.) for HRMS measurements and
Dr. F.R. Fronczek (Department of Chemistry, Louisiana State Uni-
versity, U.S.A.) for X-Ray data.
1251, 1172, 833, 748 cmꢀ1. TOF-MS EIþ: (m/z, %)¼308 (55) [M]þ, 251
(100), 235 (80), 207 (50). HRMS calculated for C19H20N2O2
308.1525; found 308.1522.
4.2.5. (R)-5-((R)-2-Methyloxiran-2-yl)-1-phenyl-3-(4-(tri-
fluoromethyl)phenyl)-4,5-dihydro-1H-pyrazole (6e) and (R)-5-((S)
-2-methyloxiran-2-yl)-1-phenyl-3-(4-(trifluoromethyl)phenyl)-4,5-
dihydro-1H-pyrazole (7e). Two separated diastereomers. Compound
6e: Light green powder (50 mg, 44%). Mp 118e120 ꢂC. Rf: 0.44
References and notes
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n
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