Formation of 2,6-Diphenyl-1,4-bis(trifluoromethylsulfonyl) piperazine in the reaction of styrene with trifluoromethylsulfonylnitrene

Article abstract of DOI:10.1134/S1070428011040166

The reaction of styrene with trifluoromethylsulfonylnitrene generated in the system t-BuOCl-NaI led to the formation of trifluoro-N-[2-phenyl-2- (trifluoromethylsulfonylamino)ethyl]methanesulfonamide CF₃SO ₂NHCH(Ph)CH₂NHSO

Full text of DOI:10.1134/S1070428011040166

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 4, pp. 568–571. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © M.Yu. Moskalik, B.A. Shainyan, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 4, pp. 565–568.
Formation of 2,6-Diphenyl-1,4-bis(trifluoromethyl-
sulfonyl)piperazine in the Reaction of Styrene
with Trifluoromethylsulfonylnitrene
M. Yu. Moskalik and B. A. Shainyan
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: bagrat@irioch.irk.ru
Received December 3, 2010
Abstract—The reaction of styrene with trifluoromethylsulfonylnitrene generated in the system t-BuOCl–NaI
led to the formation of trifluoro-N-[2-phenyl-2-(trifluoromethylsulfonylamino)ethyl]methanesulfonamide
CF3SO2NHCH(Ph)CH2NHSO2CF3, 2-iodo-1-phenylethanol, and heterocyclization product, 2,6-diphenyl-1,4-
(trifluoromethylsulfonyl)piperazine. The latter is regioisomeric to 2,5-diphenyl-1,4-(trifluoromethylsulfonyl)-
piperazine obtained previously by analogous reaction in the system t-BuOCl–NaI·2H2O.
DOI: 10.1134/S1070428011040166
We recently studied the reaction of styrene with tri-
fluoromethylsulfonylnitrene CF3SO2N: generated from
trifluoromethanesulfonamide in the system t-BuOCl–
NaI·2H2O and obtained 2,5-diphenyl-1,4-bis(trifluoro-
methylsulfonyl)piperazine (I) together with other prod-
ucts. The structure of compound I was determined by
X-ray analysis, and a probable mechanism of its forma-
tion was proposed [1]. Unexpectedly, compound I was
also obtained by dehydrobromination of N-(2-bromo-
2-phenylethyl)trifluoromethanesulfonamide (II) by the
action of triethylamine [2] (Scheme 1).
trifluoromethylsulfonylnitrene to styrene. However,
the third isolated compound (V) differed from pipera-
1
zine I obtained previously. Its H NMR spectrum con-
tained signals from aromatic protons and an ABX spin
pattern, but the HA signal was displaced by 0.3 ppm
upfield, and the HB and HX signals were located in
a weaker field (by 0.2 and 0.1 ppm, respectively)
relative to the corresponding signals in the spectrum
of I. In the 13C NMR spectrum of compound V the CH
carbon atom resonated in a stronger field (by 5 ppm),
and the most important difference from the spectrum
of I was the presence of two signals assignable to CF3
group. Correspondingly, two different signals were
observed in the 19F NMR spectrum of V. The above
data allowed us to assign compound V the structure of
2,6-diphenyl-1,4-bis(trifluoromethylsulfonyl)pipera-
zine (Scheme 2).
Compound I was not the major product in the
reaction of styrene with trifluoromethylsulfonylnitrene;
apart from I, trifluoro-N-[2-phenyl-2-(trifluoromethyl-
sulfonylamino)ethyl]methanesulfonamide (III) and
2-iodo-1-phenylethanol (IV) were formed [1]. With
a view to obtain the corresponding aziridine [3] we
modified the system t-BuOCl–NaI·2H2O and used an-
hydrous sodium iodide. The reaction occurred in a way
similar to that reported previously [1], i.e., with forma-
tion of compounds III and IV as products of opening
of the aziridine ring in the primary addition product of
Apart from the presence of signals from two
magnetically nonequivalent trifluoromethyl groups in
the NMR spectra, the unsymmetrical structure of com-
pound V was confirmed by the mass spectral data. The
exact molecular weights of I and V coincide with each
Scheme 1.
t-BuOCl, NaI·2H2O
MeCN
F3CSO2
Ph
Et3N
–HBr
N
+
CF3SO2NH2
CF3SO2NHCH2CHBrPh
Ph
CH2
N
Ph
SO2CF3
I
II
568

FORMATION OF 2,6-DIPHENYL-1,4-BIS(TRIFLUOROMETHYLSULFONYL)PIPERAZINE
569
Scheme 2.
Ph
t-BuOCl, NaI (anhydrous)
MeCN
F3CSO2
Ph
Ph
Ph
N
NHSO2CF3
NHSO2CF3
III
I
+
CF3SO2NH2
+
+
Ph
CH2
N
OH
SO2CF3
IV
V
other, i.e., these compounds are isomers. Fragmenta-
tion patterns of the molecular ions of I and V are also
similar, but the mass spectrum of V contained a frag-
ment ion peak with m/z 194 which was absent in the
spectrum of compound I. This ion has the structure
are electronic properties of the substituent in the aziri-
dine ring and the nature of nucleophile. Steric factor
and reaction conditions also play a definite role [7].
For example, 2-aryl-1-(4-methylphenylsulfonyl)aziri-
dines react with C-, O-, S-, and Hlg-nucleophiles either
exclusively or preferentially at the N–C2 bond [8–10,
14–17], whereas the N–C3 bond is cleaved in 2-alkyl-
1-(4-methylphenylsulfonyl)aziridines [18–21]. An ex-
ception is the reaction of 1-(4-methylphenylsulfonyl)-
2-phenylaziridine with benzenethiol [17], which af-
forded isomeric products resulting from opening of the
aziridine ring at the N–C2 and N–C3 bonds at a ratio of
1:1. In the reactions with indium halides, the above
ratio of regioisomers decreases as the size of the halo-
gen atom rises [19]. The reaction with participation of
NaI·2H2O (path a in Scheme 3) involves opening of
the aziridine ring by the action of a large solvated
iodide ion and sterically hindered nitrogen-centered
nucleophile [CF3SO2NCH(Ph)CH2I]–, which is likely
to occur at the N–C3 bond at each step; as a result,
isomer I is formed. In the reaction with anhydrous
sodium iodide (path b), attack by less bulky unsolvated
iodide ion can be directed at C2 to produce isomeric
anion [CF3SO2NCH2CH(Ph)I]– and then isomer V.
[PhCH
N
CHPh]+; obviously, it cannot be
formed from isomer I.
The mechanism of formation of compound I in the
reaction of styrene with trifluoromethylsulfonylnitrene
involves double opening of the three-membered ring in
intermediate 1-(trifluoromethylsulfonyl)-2-phenylaziri-
dine [1] (Scheme 3). If cleavage of the aziridine ring
occurs each time via dissociation of the N–CH2 bond
[4–6] and nucleophile addition to the unsubstituted
carbon atom (path a in Scheme 3), symmetric pipera-
zine I is formed [1]. If cleavage of the N–CH(Ph) bond
occurs at one step (path b), as in the reaction of struc-
turally related 1-(4-methylphenylsulfonyl)-2-phenylaz-
iridine with Me3SiN3 [6], isomeric unsymmetrically
substituted piperazine V is obtained.
Analysis of recently published data on reactions of
N-sulfonylaziridines with nucleophiles [4–21] showed
that the main factors determining the reaction direction
Scheme 3.
Ph
Ph
N
F3CSO2
I
F3CSO2
Ph
Ph
SO2CF3
N
N
F3CSO2
I
–I–
a
N
N
N
SO2CF3
SO2CF3
Ph
Ph
I–
I
Ph
N
SO2CF3
I–
Ph
Ph
N
F3CSO2
Ph
I
F3CSO2
Ph
Ph
SO2CF3
N
N
F3CSO2
I
N
–I–
b
N
N
SO2CF3
SO2CF3
Ph
V
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 4 2011

MOSKALIK, SHAINYAN
blet with 1JCH = 154.4 Hz, and the CH2 signal was split
570
into 8 lines due to coupling with diastereotopic
methylene protons (1JCH = 142.2, 144.0 Hz) and CH
proton (2JCH = 4.1 Hz). The observed direct coupling
1
constants JCH are much smaller than those typical of
aziridines (>170 Hz [23]). Likewise, the 13C NMR
spectrum of the crude product obtained by aziridina-
tion of styrene with methanesulfonamide according to
[3] contained multiplet signals with coupling constants
1JCH of 155–157 Hz. These findings indicate the neces-
sity of more thorough examination of the conditions
for aziridination of alkenes in the system sulfonamide–
tert-butyl hypochlorite–sodium iodide.
EXPERIMENTAL
2,5-Twist conformation of the piperazine ring in molecule V,
optimized by the B3LYP/6-311G** method.
The IR spectrum of compound V was recorded on
a Bruker Vertex 70 spectrometer with Fourier trans-
form. The NMR spectra were measured from solutions
in CD3CN on a Bruker DPX 400 spectrometer at 400
(1H), 100 (13C), and 376 MHz (19F); the chemical shifts
were determined relative to tetramethylsilane (1H, 13C)
and CCl3F (19F). The mass spectra (electron impact,
70 eV) were obtained on a GC-MS TRACE DSQ II
instrument (Thermo Fisher Scientific GmbH) with
direct sample admission into the ion source. The high-
resolution mass spectrum was recorded on a Waters
Micromass Q-TOFmicro spectrometer (positive electro-
spray); a sample was introduced using a Harvard
syringe pump (20 μl/min); capillary entrance voltage
3.2 kV, cone voltage 20–25 V. The elemental composi-
tions were determined from the precise molecular
weights with an accuracy of <3 ppm; H3PO4 was used
as reference. The progress of reactions and separation
of products were monitored by TLC on silica gel 60 F-
254 plates using hexane–diethyl ether (1:2) as eluent.
According to the X-ray diffraction data and quan-
tum-chemical calculations, the piperazine ring in mole-
cule I has 2,5-twist rather than chair conformation due
to the presence of two neighboring bulky groups [1].
Even stronger steric strain might be expected for com-
pound V where bulky substituents are attached to three
contiguous atoms. In fact, B3LYP/6-311G** calcula-
tions (see figure) also predicted 2,5-twist conformation
of the piperazine ring in isomer V, the total energy of
V being higher by 6.1 kcal/mol than that of I.
As we noted previously [1], elemental analysis and
routine NMR spectroscopy cannot distinguish between
aziridines and piperazines formed by their dimerization
[22]; for this purpose, X-ray analysis or at least meas-
urement of direct carbon–proton coupling constants
1JCH is necessary. The failure to isolate aziridines in the
reaction of styrene with trifluoromethylsulfonylnitrene
in this and previous [1] works prompted us to repro-
duce the syntheses of aziridines via reactions of sty-
rene with methanesulfonamide and 4-methylbenzene-
sulfonamide, rigorously following the conditions
reported in [3].
Reaction of trifluoromethylsulfonylnitrene with
styrene. tert-Butyl hypochlorite, 6.5 g (0.06 mmol),
was added dropwise to a solution of 3 g (0.02 mmol)
of trifluoromethanesulfonamide, 2.09 g (0.02 mmol) of
styrene, and 9 g (0.06 mmol) of anhydrous sodium
iodide in 120 ml of acetonitrile. The mixture was
stirred for 12 h at –10°C in the dark under nitrogen,
treated with 120 ml of a 0.3 M solution of Na2S2O3,
and extracted with a mixture of acetonitrile and ethyl
acetate. The extract was dried over CaCl2, the solvent
was distilled under reduced pressure, and the residue,
~4.5 g of a liquid tarry material, was subjected to col-
umn chromatography on silica gel (grain size 0.063–
0.200 mm). The column was eluted with hexane to
13
In the C NMR spectrum of the crude product ob-
tained in the reaction of styrene with 4-methylbenzene-
sulfonamide we observed signals assignable to the
target aziridine (δC 35.86 and 41.18 ppm), but its
amount was estimated at a trace level (~5%). The ma-
jor signals were observed at δC 30.53 and 51.29 ppm,
and they had similar intensities and were assigned to
CH and CH2 carbon atoms. In the proton-coupled
13C NMR spectrum, the CH signal was split into a dou-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 4 2011

FORMATION OF 2,6-DIPHENYL-1,4-BIS(TRIFLUOROMETHYLSULFONYL)PIPERAZINE
571
no. 10-03-00110). The authors are grateful to E. Klein-
peter (Institut für Chemie, Universität Potsdam) for
recording the mass spectra of compound V.
remove tars and separate a mixture of compounds IV
and V from compound III. Compounds IV and V were
separated by repeated chromatography on silica gel
(grain size 0.015–0.040 mm) using hexane as eluent.
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fonylamino)ethyl]methanesulfonamide (III). Yield
2 g (50%), colorless crystals. The melting points and
IR and NMR spectra of III coincided with the data
reported by us previously [1].
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piperazine (V). Yield 0.4 g (8%), colorless crystals,
mp 199–202°C (from hexane). IR spectrum, ν, cm–1:
3059, 3021, 1955, 1605, 1501, 1470, 1453, 1395,
1375, 1229, 1176, 1151, 1051, 956, 875, 742, 709,
1
692, 674, 605. H NMR spectrum, δ, ppm: 3.73 d.d
(1H, CH2, J = 13.8, 3.6 Hz), 4.62 d (1H, CH2, J =
13.8 Hz), 5.42 d (1H, PhCH, J = 3.6 Hz), 7.05 m (3H,
13
m-H, p-H), 7.25 m (2H, o-H). C NMR spectrum, δC,
ppm: 48.47 (CH2, 1JCH = 145.57 Hz), 56.5 (CH, 1JCH
=
141.89 Hz), 121.05 q (1-CF3, JCF = 324.22 Hz),
121.14 q (4-CF3, JCF = 322.38 Hz), 128.41 (Co),
19
128.78 (Cp), 128.96 (Cm), 136.58 (Ci). F NMR spec-
trum, δF, ppm: –76.11 (4-CF3), –73.98 (1-CF3). Mass
spectrum, m/z (Irel, %): 502 (16) [M]+, 369 (8) [M –
CF3SO2]+, 235 (20) [369 – CF3SO2H]+, 194 (13)
[(PhCH)2N]+, 117 (14) [194 – Ph]+, 104 (85) [PhCHN]+,
91 (28) [PhCH2]+, 77 (16) [Ph]+, 69 (37) [CF3]+,
41 (100) [C2H3N]+. Found: m/z 502.0461 [M]+.
C18H16F6N2O4S2. Calculated: M 502.0450.
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This study was performed under financial support
by the Russian Foundation for Basic Research (project
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 4 2011