One-step synthesis of diazadihydroacenaphthylene derivatives with an isoxazoline ring, starting from 1-benzylamino-1-methylsulfanyl-2-nitroethenes

Article abstract of DOI:10.1016/j.tetlet.2006.03.003

At low temperature in trifluoromethanesulfonic acid, 1-benzylamino-1-methylthio-2-nitroethene derivatives form hydroxynitrilium ions (or O-protonated nitrile oxides) observed by NMR. Quenching with water leads to the formation of a reactive nitrile oxide,

Full text of DOI:10.1016/j.tetlet.2006.03.003

Tetrahedron Letters 47 (2006) 3315–3319
One-step synthesis of diazadihydroacenaphthylene
derivatives with an isoxazoline ring, starting from
1-benzylamino-1-methylsulfanyl-2-nitroethenes
a
b
a
b,
*
´
Yaya Soro, Fante Bamba, Sorho Siaka and Jean-Marie Coustard
a
`
Laboratoire des Proce´de´s Industriels de Synthese et d’Environnement,
Institut National Polytechnique Fe´lix Houphoue¨t-Boigny, BP 991 Yamoussoukro, Cote d’Ivoire
`
´ ´
Laboratoire ‘Synthese et Reactivite des Substances Naturelles’, UMR CNRS 6514 40, Avenue du Recteur Pineau,
b
F-86022 Poitiers Cedex, France
Received 27 January 2006; revised 27 February 2006; accepted 1 March 2006
Available online 24 March 2006
Abstract—At low temperature in trifluoromethanesulfonic acid, 1-benzylamino-1-methylthio-2-nitroethene derivatives form
hydroxynitrilium ions (or O-protonated nitrile oxides) observed by NMR. Quenching with water leads to the formation of a reactive
nitrile oxide, dipole which undergoes an unexpected INOC reaction leading to new 3-methylsulfanyl-8a,8b-dihydro-5H-1-oxa-2,4-
diazaacenaphthylenes.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
aldoxime oxidation with hypochlorite. Nitrile oxides
can either be prepared in situ, or prepared in advance
in the case of the more stable derivatives, for example,
substituted phenylnitrile oxide.
Isoxazoline derivatives are an important class of hetero-
cyclic compounds and their chemical properties have
been studied over the years.1 They are versatile scaffolds
for the synthesis of a wide variety of complex natural
products2 and important pharmacophore in therapeutic
chemistry.3,4
Recently, Corsaro et al.11 reported the dipolarophilic
reactivity of polycyclic aromatic hydrocarbons and their
aza-analogues in 1,3-dipolar cycloadditions, which gave
mainly monocycloadducts with partial destruction of
the aromaticity.
Isoxazoline derivatives are also known to exhibit inter-
esting biological activities in the agricultural field5 and
possess medicinal properties including anticancer, anti-
biotic6 or antiviral and anti-HIV activities.7
In previous papers,12–14 the observation of stable
hydroxynitrilium ions from 1-heterosubstituted-2-
nitroethene in trifluoromethanesulfonic acid at low
temperature was reported. In the particular case of
1,1-bis(methylthio)-2-nitroethylene 1 and its derivatives
2 and 3, the corresponding hydroxynitrilium ions 4
were characterized by their NMR spectra in superacid.
Cation 4 may either react in situ as an electrophilic
species or during quenching as a new source of nitrile
oxide 5 (Scheme 1).
One of the most general methods used to prepare isox-
azoline derivatives involves 1,3-dipolar cycloaddition
between nitrile oxides and olefins.8 Nitrile oxide can be
prepared from primary nitro compounds with phenyliso-
cyanate/triethylamine (Et3N),9 or by deshydrohalogen-
ation of oximinoyl halides10 (Huisgen procedure)
obtained from the reaction of aldoximes with NCS,
NBS, halogens and chlorobenzotriazole or from direct
In the present letter, the use of trifluoromethanesulf-
onic acid (or triflic acid) and 1-benzylamino-1-methyl-
sulfanyl-2-nitroethenes is reported to prepare the
corresponding 3-methylsulfanyl-8a,8b-dihydro-5H-1-oxa-
2,4-diazaacenaphthylenes, a new class of oxazoline
Keywords: Benzylaminonitroethenes; (Protonated) nitrile oxide; Nitrile
oxide 1,3-dipolar cycloaddition; Superacid; Acenaphthylene isoxazoline.
*
Corresponding author. Tel.: +33 0549 454 100; fax: +33 0549 453
501; e-mail: jean.marie.coustard@univ-poitiers.fr
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.003

3316
Y. Soro et al. / Tetrahedron Letters 47 (2006) 3315–3319
R
NO2
R
R
+
+
-
O
+
N
OH
+
N
MeS
MeS
MeS
4
1 R = MeS
5
2 R = ArNH
3 R = Ph(CH2)1-4
S
Scheme 1. Formation of nitrile oxide from 1-substituted-2-nitroethene derivatives.
derivatives. The observed reaction is an unusual intra-
molecular nitrile oxide cyclization (INOC reaction) that
occurs on a single phenyl ring with the full loss of aro-
maticity of the molecule. This is, to our best knowledge,
the first example reported of a direct addition of nitrile
oxide on a monosubstituted monoaromatic phenyl ring.
fully transformed within 0.5–6.25 h of reaction time,
depending on the substituent. At the end of the reaction,
the acidic solution was poured onto a mixture of ice
(10 g) and anhydrous Na2CO3 (6 g) and the extraction
was carried out promptly at approximately 0 ꢁC with
dichloromethane (3 · 20 mL).17 These reactions were
clean, except for the fluoro compound 7d. The observed
reaction is reported in Scheme 3.
2. Results and discussion
2.1. Starting compounds
The formed 3-methylsulfanyl-8a,8b-dihydro-5H-1-oxa-
2,4-diazaacenaphthylenes 8a–d were separated by
column chromatography and purified by crystallization.
The yields are in the range of 41–57% as indicated in
Table 1, with the lowest being that for the fluoro
compound (R = F).
The starting 1-benzylamino-2-nitroethylenes 7a–d were
prepared by nucleophilic substitution between the corre-
sponding para-substituted benzylamine 6a–d and 1,1-
bis(methylthio)-2-nitroethylene 1 (1.1 molar equivalent)
in refluxing 95% ethanol15 (Scheme 2).
The NMR spectra of cyclized compounds 8a–d are char-
acterized by two kinds of protons, in the range of 4.19–
4.38 ppm and 5.19–5.66 ppm, for H-8b and H-8a,
The yields of 7a–d vary from 65% to 75% with no
particular influence from the para-substituent on the
aromatic ring (Table 1). Some N,N-disubstituted
derivatives were also formed as by-products during the
reaction.
3
respectively. The JHH coupling constants are close to
15 Hz, a value which is characteristic of a cis configura-
tion and in agreement with previously reported values
for isoxazolines of this kind.11 Vinylic protons resonate
between 5.19 and 5.91 ppm and the C–H carbons of the
oxazolidine ring at dC 47.1–51.4 ppm and 77.2–82.0 ppm
(C-8b and C-8a, respectively) and close to previously
reported values (Table 1).11
1
Compounds 7a–d were characterized from their H and
13C NMR spectra, with vinylic protons in the range of
dH 6.58–6.60 ppm and the C-1 and C-2 carbons at dC
164.8–165.9 and 107.0–107.2 ppm, respectively. A single
set of signals was observed for each benzylaminonitro-
ethene 7a–d, which may imply that a sole isomer was
present in the solution. This is probably the (E)-isomer
as previously reported for 1-arylamino-1-methylsulfan-
yl-2-nitroethene 2.16 This configuration allows the for-
mation of an intramolecular hydrogen bond between
the N–H and one of the oxygen atoms of the planar
–NO2 group.
When dissolved in triflic acid, 1-heterosubstituted-2-
nitroethene derivatives undergo a double protonation:
one occurs on the oxygen of the nitro group, with a fast
proton exchange18, and the second on carbon 2 with
double bond migration to form a CH2 group. This
transient dication undergoes prototropic rearrange-
ments, and the loss of a molecule of water, to afford
the hydroxynitrilium group (or O-protonated nitrile
oxide). Such hydroxynitrilium cations were previously
observed with 1,1-heterodisubstituted-2-nitroethylene
derivatives using NMR.12–14 They are electrophilic
species, which can react in situ either with nucleophilic
In the present study, the reactions were carried out in
trifluoromethanesulfonic acid at low temperature (À30
to À10 ꢁC) and under nitrogen atmosphere. The molar
ratio of trifluoromethanesulfonic acid/benzylamino-
nitroethenes 7a–d was 50:1. The starting material was
À
À
14a
12
anions (CF3SO3 in triflic acid
or F in HF-SbF5 )
or with aromatic rings.
R
R
NO2
H
MeS
MeS
NO2
95 % Ethanol
+
N
NH2
Reflux, 2 - 4 h
SMe
1
6a R = H
b R = OMe
c R = Me
d R = F
7a-d
Scheme 2. Synthesis of monosubstituted products 7a–d.

Y. Soro et al. / Tetrahedron Letters 47 (2006) 3315–3319
Table 1. Yields and data for compounds 7a–d and cyclized products 8a–d
3317
Compd
R
H
Yielda (%) 1H NMR (CDCl3, 300 MHz) and 13C NMR (CDCl3, 75 MHz) d (ppm), J (Hz) Mp (ꢁC) HRMS ([M+])
7a
75
1H NMR: 2.41 (s, 3H, CH3), 4.61 (d, J = 5.9 Hz, 2H, CH2), 6.58
(s, 1H, vinylic H), 7.28–7.31 (m, 2H, Ar), 7.32–7.36 (m, 2H, Ar),
7.37–7.38 (m, 1H, Ar), 10.76 (broad s, NH)
122.4
94.9
93.3
C10H12N2O2S,
calcd 224.0619,
found 224.0621
13C NMR: 14.9 (SCH3), 48.7 (CH2), 107.1 (@CH–NO2), 127.8
(Ar CH), 129.5 (Ar CH), 135.9 (ipso-C), 165.1 (–NH–C@)
7b
7c
OMe 72
1H NMR: 2.35 (s, 3H, SCH3), 2.44 (s, 3H, CH3), 4.59 (d, J = 5.9 Hz,
2H, CH2), 6.60 (s, 1H, vinylic H), 7.19 (m, 4H, Ar), 10.70 (broad s, NH)
13C NMR: 14.9 (SCH3), 21.6 (CH3), 48.5 (CH2), 106.9 (@CH–NO2),
127.8 (Ar CH), 130.1 (Ar CH), 132.8 (ipso-C-Me), 138.54 (ipso-C),
165.08 (–NH–C@)
C11H14N2O2S,
calcd 238.0776,
found 238.0765
Me
65
69
57
1H NMR: 2.44 (s, 3H, SCH3), 3.81 (s, 3H, CH3), 4.56 (d, J = 5.9 Hz,
2H, CH2), 6.60 (s, 1H, vinylic H), 6.89 (d, J = 2.1 Hz, 1H, Ar), 6.92
(d, J = 2,2 Hz, 1H, Ar), 7.22 (d, J = 2.2 Hz, 1H, Ar), 7.25
(d, J = 2.1 Hz, 1H, Ar), 10.73 (broad s, 1H, NH)
13C NMR: 14.9 (SCH3), 48.3 (CH2), 55.7 (OCH3), 106.9 (@CH–NO2),
114.8 (Ar CH), 127.8 (Ar CH), 129.3 (ipso-C), 160.0 (ipso-C OMe),
164.8 (–NH–C@)
C11H14N2O3S,
calcd 254.0725,
found 254.0734
7d
F
1H NMR: 2.45 (s, 3H, SCH3), 4.61 (d, J = 5.9 Hz, 2H, CH2), 6.60
(s, 1H, @CH–NO2), 7.04–7.10 (ct, Japp = 8.6 Hz, 2H, Ar), 7.26–7.30
(m, 2H, Ar), 10.71 (broad s, 1H, NH)
119.9
C10H11FN2O2S,
calcd 242.0525,
found 242.0527
13C NMR: 14.9 (SCH3), 48.0 (CH2), 107.2 (@CH–NO2), 116.4
2
3
(d, JCF = 21.9 Hz, Ar CH), 129.7 (d, JCF = 8.2 Hz, Ar CH), 131.7
4
1
(d, JCF = 3.3 Hz, ipso-C), 162.9 (d, JCF = 247.0 Hz, ipso-C-F),
164.9 (–NH–C@)
8a
8b
8c
8d
H
1H NMR: 2.39 (s, 3H, SCH3), 4.19 (d, J = 14.9 Hz, 1H, H-8b), 4.50
(s, 2H, CH2), 5.62 (dd, J = 14.9 and 4.3 Hz, 1H, H-8a), 5.89 (m, 2H,
vinylic H), 6.19 (dd, J = 9.8 and 5.9 Hz, 1H, vinylic H)
13C NMR: 11.7 (SCH3), 47.1 (C-8b), 58.0 (CH2), 77.7 (C-8a), 117.0
(@CH), 120.3 (@CH), 126.5 (@CH), 126.8 (quaternary C, C-5a),
151.8 (>C@N–O–), 155.0 (–S–C@N–)
108.8
120.1
132.5
98.7
C10H10N2OS,
calcd 206.0514,
found 206.0507
OMe 44
1H NMR: 2.39 (s, 3H, SCH3), 3.66 (s, 3H, OCH3), 4.25 (d, J = 14.6 Hz,
1H, H-8b), 4.46 (m, 2H, CH2), 5.19 (d, J = 6.7 Hz, 1H, vinylic H), 5.52
(d, J = 14.6 Hz, 1H, H-8a), 5.83 (d, J = 6.7 Hz, 1H, vinylic H)
13C NMR: 12.1 (SCH3), 49.8 (C-8b), 55.7 (OCH3), 58.3 (CH2), 79.2 (C-8a),
95.6 (@CH, C-7), 117.6 (@CH, C-6), 119.8 (quaternary C, C-5a), 152.6
(ipso OMe, C-8), 153.2 (>C@N–O–), 155.2 (–S–C@N–)
C11H12N2OS,
calcd 220.0670,
found 220.0680
Me
44
41
1H NMR: 2.01 (s, 3H, CH3), 2.39 (s, 3H, SCH3), 4.23 (d, J = 14.9 Hz, 1H,
H-8b), 4.47 (s, 2H, CH2), 5.46 (d, J = 14.9 Hz, 1H, H-8a), 5.81 (d, J = 7.1 Hz,
1H, vinylic H), 5.84 (d, J = 7.1 Hz, 1H, vinylic H)
13C NMR: 12.0 (SCH3), 21.1 (CH3), 48.0 (C-8b), 58.4 (CH2), 82.0 (C-8a), 117.8
(@CH, C-6), 121.7 (@CH, C-7), 124.8 (quaternary C, C-5a), 130.4
(C ipso Me, C-8), 152.6 (>C@N–O–), 155.4 (–S–C@N–)
C11H12N2O2S,
calcd 236.0619,
found 236.0619
F
1H NMR: 2.40 (s, 3H, CH3), 4.38 (d, J = 14.94 Hz, 1H, H-8b), 4.51 (m, 2H,
CH2), 5.66 (dd, J = 14.9 and 4.95 Hz, 1H, H-8a), 5.81 (m, 2H, vinylic H)
C10H9FN2OS,
calcd 224.0420,
found 224.0425
3
13C NMR: 12.2 (SCH3), 51.4 (d, JCF = 8.2 Hz, C–H, C-8b), 58.1 (CH2, C-5),
2
2
77.2 (d, JCF = 27.6 Hz, C–H, C-8a), 105.5 (d, JCF = 19.2 Hz, C–H, C-7),
3
4
115.9 (d, JCF = 6.0 Hz, C–H, C-6), 123.8 (d, JCF = 6.0 Hz, quaternary C,
C-5a), 152.1 (d, JCF = 2.2 Hz, >C@N–O–), 155.1 (S–C@N–), 156.3
4
1
(d, JCF = 266.7 Hz, C ipso F, C-8)
a Yields after crystallization/Ar was used for aromatic.
In the present case, nitro derivatives 7 are transformed
into hydroxynitrilium ion 9 which do not react, even
by an intramolecular process, probably because of the
excessively high activation energy of the reaction at this
low temperature. Indeed, NMR spectroscopic analysis
indicates that nitro derivative 7a affords ion 9a as the
sole species in trifluoromethanesulfonic acid, in a few
minutes at 255 K. This species is mainly characterized
by the hydroxynitrilium carbon, which resonates at
24.9 ppm as a broad and very weak signal,19 in agree-
ment with previously reported values.12–14 The broaden-
ing and weakening of the carbon signal is firstly due to
coupling with 15N, but secondly, mainly to a quadru-
polar relaxation with 14N, the most abundant isotope.20
By quenching with water, the high acidity is destroyed
and the hydroxynitrilium ion 9 is transformed into a reac-
tive nitrile oxide 10, which undergoes an intramolecular

3318
Y. Soro et al. / Tetrahedron Letters 47 (2006) 3315–3319
1
O
N
H
R
NO2
H
SMe
R
8a
1) CF SO H, - 30 to -10
C
˚
3
3
3
8b
N
H
N
2) Na2CO3 / H2O
SMe
7a-d
8a-d
Scheme 3. Cyclization of compounds 7a–d in trifluoromethanesulfonic acid.
R
+
HO
+
H
N
NO2H
N
CF3SO3H
+
R
SMe
7a-d
H
H
+
NH
SMe
Transient dication
9
Stable at low temperature
Quenching
-
O
N
+
O
H
N
SMe
R
R
SMe
H
N
N
8a-d
10
Scheme 4. Suggested mechanism for the formation of compounds 8a–d.
1,3-dipolar cycloaddition (INOC reaction) to afford the
cyclized products 8a–d. The suggested reaction pathway
is depicted in Scheme 4.
References and notes
1. (a) Ja¨ger, V.; Buss, V. Liebigs Ann. Chem. 1980, 101–121;
(b) Ja¨ger, V.; Buss, V.; Schwab, W. Liebigs Ann. Chem.
1980, 122–139.
2. (a) Saha, A.; Bhattacharjya, A. Chem. Commun. (Cam-
bridge) 1997, 495–496; (b) Copp, B. R.; Ireland, C. M.;
Barrows, L. R. J. Nat. Prod. 1992, 55, 822–823.
3. (a) Brandi, A.; Cicchi, S.; Cordero, F. M.; Goti, A. Chem.
Rev. 2003, 103, 1213–1269; (b) King, S. W.; Riordan, J.
M.; Holt, E. M.; Stammer, C. H. J. Org. Chem. 1982, 47,
3270–3273.
4. (a) Bacher, E.; Demnitz, F. W. J.; Hurni, T. Tetrahedron
1997, 53, 14317–14326; (b) Zhengqing, Y.; Khalil, M. A.;
Dong-Hoon, K.; Lee, H. J. Tetrahedron Lett. 1995, 36,
3303–3306.
5. Liu, K. C.; Howe, R. K. J. Org. Chem. 1983, 48, 4590–
4592.
6. (a) Amgad, G. H.; Praveen Rao, P. N.; Edward, E. K. J.
Med. Chem. 2001, 44, 2921–2927; (b) Mallesha, H.; Ravi
kumar, K. R.; Mantelingu, K.; Rangappa, K. S. Synthesis
2001, 10, 1459–1461.
3. Conclusion
A novel methodology has been developed for the syn-
theses of tricyclic 3-methylsulfanyl-8a,8b-dihydro-5H-
1-oxa-2,4-diazaacenaphthylenes with an isoxazoline ring
from 2-nitroethene derivatives, using trifluoromethane-
sulfonic acid. The mechanism of the reaction implies
the formation of a stable hydroxynitrilium ion (or O-
protonated nitrile oxide) in superacid, the quenching
of which leads to a reactive nitrile oxide. An intramole-
cular 1,3-dipolar cycloaddition (INOC) with the phenyl
ring affords tricyclic non-aromatic isoxazoline. To the
best of our knowledge, it is the first time that is reported
the reaction of a nitrile oxide with a monosubstituted
phenyl ring to form isoxazoline, with a full loss of
aromaticity.
7. Ichiba, T.; Scheuer, P. J. J. Org. Chem. 1993, 58, 4149–
4150.
8. (a) Pedro, A. C.; Ja¨ger, V.; Albrecht, L.; Rodolfo, D. B.
Tetrahedron Lett. 2003, 44, 1071–1074; (b) Patrick, Y. S.
L.; Jessica, J. A.; Charles, G. C.; Calhoun, W. J.;
Luettgen, J. M.; Knabb, R. M.; Wexler, R. R. Bioorg.
Med. Chem. Lett. 2003, 13, 1795–1799; (c) Basappa;
Sadashiva, M. P.; Swamy, S. N.; Rangappa, K. S. Bioorg.
Med. Chem. Lett. 2003, 11, 4539–4544.
The 3-methylsulfanyl-8a,8b-dihydro-5H-1-oxa-2,4-diaza-
acenaphthylenes can be used as synthons and further
work is in progress in this field.
Acknowledgements
9. (a) Cecchi, L.; De Sarloa, F.; Machettib, F. Tetrahedron
Lett. 2005, 46, 7877–7879; (b) Shang, Y. J.; Wang, Y. G.
Tetrahedron Lett. 2002, 43, 2247–2249; (c) Shang, Y. J.;
Wang, Y. G. Synthesis 2002, 12, 1663–1668.
Thanks to CNRS (France) for financial support and to
`
`
‘Ministere des Affaires Etrangeres—France’ for fellow-
ship funds for some of us (Y.S. and S.S.).

Y. Soro et al. / Tetrahedron Letters 47 (2006) 3315–3319
3319
10. (a) Christl, M.; Huisgen, R. Chem. Ber. 1973, 106, 3345–
3367; (b) Huisgen, R. In 1,3-Dipolar Cycloaddition Chem-
istry; Padwa, A., Ed.; Wiley: New York, 1984; Vol. 1, pp
291–392; (c) Gi, H.-J.; Xiang, Y.; Shinazi, R. F.; Zhao, K.
J. Org. Chem. 1997, 62, 88–92.
(4 mL, 45 mmol) at À26 to À23 ꢁC under nitrogen
atmosphere. The reaction was monitored as follows: one
or two drops of the reacting medium were quenched over
ice (about 1 g)/Na2CO3 and extracted with CH2Cl2
(0.5 mL). The organic phase extract was analyzed by
TLC (Silica gel on aluminum sheet ‘Alugramꢂ Sil G/
`
11. (a) Corsaro, A.; Librando, V.; Chiacchio, U.; Pistara, V.
Tetrahedron 1996, 52, 13027–13034; (b) Librando, V.;
Chiacchio, U.; Corsaro, A.; Gumina, G. Polycycl. Aromat.
Compd. 1996, 11, 313–316; (c) Corsaro, A.; Librando, V.;
UV254 fur die DC’, Art.-Nr. 818 133 from Macherey-
¨
Nagel, eluent CH2Cl2:MeOH 99/1). NMR at low temper-
ature was also used as an alternative method (external
reference: TMS in acetone-d6 or methanol-d4 in a sealed
capillary tube inside the NMR cell). After disappearance
of the starting compound (ꢀ0.5 h), the solution was
poured into 80 mL of CH2Cl2/MeOH (87:13) at À60 to
À40 ꢁC. The resulting mixture was poured over ice (10 g)
and Na2CO3 and extracted with CH2Cl2 (3 · 20 mL). The
organic phase was dried over MgSO4 and the solvent
evaporated under reduced pressure. The crude product
was purified by flash chromatography with dichlorometh-
ane and then crystallized from CH2Cl2/petroleum ether to
afford 8a (116 mg, 57%) as light white crystals.
`
Chiacchio, U.; Fisichella, S.; Pistara, V. Heterocycles
1997, 45, 1567–1572; (d) Corsaro, A.; Librando, V.;
`
Chiacchio, U.; Pistara, V.; Rescifina, A. Tetrahedron
`
1998, 54, 9187–9194; (e) Corsaro, A.; Pistara, V.; Resci-
fina, A.; Piperno, A.; Chiacchio, M. A.; Romeo, G.
Tetrahedron 2004, 60, 6443–6451.
12. Coustard, J.-M. Tetrahedron 1995, 51, 10929–10940.
13. Coustard, J.-M. Tetrahedron 1996, 52, 9505–9520.
14. (a) Coustard, J.-M. Tetrahedron 1999, 55, 5809–5820; (b)
Cousson, A.; Coustard, J.-M. Tetrahedron 1998, 54, 6523–
6528; (c) Coustard, J.-M. Eur. J. Org. Chem. 2001, 1525–
1531.
15. Typical procedure for nitroethene derivatives 7: 1,1-
bis(methylthio)-2-nitroethene (2.2 g, 13.32 mmol) and ben-
zylamine 6a (1.35 mL, 12.36 mmol) were heated together in
refluxing 95% ethanol (75 mL) under nitrogen atmosphere.
The reaction was followed by thin-layer chromatography
(CH2Cl2). After disappearance of the benzylamine (4 h)
and cooling, the mixture was concentrated under reduced
pressure and the resulting oily product was purified by flash
chromatography with dichloromethane and then crystal-
lized from CH2Cl2/petroleum ether to afford 7a (2.07 g,
75%) as yellow crystals.
18. (a) Olah, G. A.; Kiovsky, T. E. J. Am. Chem. Soc. 1968,
90, 6461–6464; (b) Olah, G. A.; Fung, A. P.; Rawdah, T.
N. J. Org. Chem. 1980, 45, 4149–4153.
19. NMR spectra of cation 9a in triflic acid at 255 K: 1H
NMR (reference: TMS in external acetone-d6): dH 2.07 (s,
3
3H, S-CH3); 3.85 (d, JH = 5.4 Hz, 2H, –CH2-Ph); 6.27–
6.35 (broad multiplet, 5H, aromatic H), 8.91 (broad
3
triplet, JH = 5.4 Hz, 1H, @N+–H); 13C NMR (reference:
external acetone-d6): dC 16.83 (–S–CH3), 24.9 (weak and
broad signal from 23.9 to 25.9, –C„N+–OH), 53.47
(–CH2–); 128.56 and 129.06 (o- and m-aromatic CH),
129.28 (IPSO aromatic C), 129.69 (p-aromatic CH),
166.82 (˜C@NH+–CH2–).
16. Kearney, T.; Harris, P. A.; Jackson, A.; Joule, J. A.
Synthesis 1992, 8, 769–772.
17. Typical procedure for isoxazoline derivatives 8: 1-benz-
ylamino-1-methylthio-2-nitroethene 7a (220 mg, 0.982
mmol) was dissolved in trifluoromethanesulfonic acid
20. (a) De Sarlo, S.; Brandi, A.; Guarna, A.; Niccolai, N. J.
Mag. Res. 1982, 50, 64–70; (b) Christi, M.; Warren, J. P.;
Hawkins, B. L.; Roberts, J. D. J. Am. Chem. Soc. 1973,
95, 4392–4397.