Heterocyclization of trans-1,2,3-triphenylcyclopropane using nitrous acid

Full text of DOI:10.1007/s10593-012-0911-8

Chemistry of Heterocyclic Compounds, Vol. 47, No. 10, January, 2012 (Russian Original Vol. 47, No. 10, October, 2011)
HETEROCYCLIZATION OF trans-1,2,3-TRIPHENYL-
CYCLOPROPANE USING NITROUS ACID
R. A. Gazzaeva1*, A. N. Fedotov2, and S. S. Mochalov2
Keywords: nitrous acid, trans-4-(4-nitrophenyl)-3,5-diphenyl-4,5-dihydroisoxazole, 4-(4-nitrophenyl)-
3,5-diphenylisoxazole, trans-3,4,5-triphenyl-4,5-dihydroisoxazole, trans-triphenylcyclopropane, hetero-
cyclization.
It is known that phenyl- and 1,2-diphenylcyclopropanes react readily with an equivalent of nitrous acid
to form 5-phenyl- and 3,5-diphenyl-4,5-dihydroisoxazoles. The geometry of the benzene rings in the 1,2-di-
phenylcyclopropanes has virtually no effect on the yield of the corresponding heterocycles [1, 2]. Since not only
mono- and disubstituted isoxazolines and isoxazoles but also triarylisoxazolines (and isoxazoles) are of interest
for practical use [3], but synthetic methods of the latter are quite limited, we have tried to find out whether 1,2,3-tri-
phenylcyclopropanes are converted to products of N=O fragment insertion into the three-carbon ring by the
action of nitrous acid using the conditions reported in [1, 2].
It was shown that treatment of trans-1,2,3-triphenylcyclopropane (1) with an equivalent amount of
sodium nitrite in trifluoroacetic acid gave only trans-3,4,5-triphenyl-4,5-dihydroisoxazole (2). This result shows
that triphenylcyclopropanes can be used successfully in the synthesis of the corresponding isoxazolines.
Ph
Ph
Ph
Ph
H
H
NaNO2, CF3COOH
CHCl3,
4-O2NC6H4
N
Ph
Ph
N
4-O2NC6H4
Ph
N
O
O
0°C
O
Ph
Ph
H
Ph
H
1
2
4
3
We have previously reported that dihydroisoxazoles prepared from phenylcyclopropanes using an
equivalent of HNO2 can be oxidized to the corresponding isoxazoles using one equivalent of this reagent [4].
These same arylisoxazoles can also be directly formed from arylcyclopropanes if two equivalents of nitrous acid
are used [4, 5]. It was found that reaction of hydrocarbon 1 with two equivalents of HNO2 does not give rise to
3,4,5-triphenylisoxazole but, in this case, yields isoxazoline 2 (81%) and trans-3,5-diphenyl-4-(4-nitrophenyl)-
4,5-dihydroisoxazole (3) (14%). Hence 3,4,5-triphenyl-4,5-dihydroisoxazole (2) behaves anomalously
_______
*To whom correspondence should be addressed, e-mail: gazzaevar@mail.ru.
1K. L. Khetagurov North-Ossetian State University, 46 Vatutin St., Vladikavkaz 362000, Russia.
2M. V. Lomonosov Moscow State University, Build. 1-3 Leninskiye Gory, Moscow 119991, Russia; e-mail:
ssmoch@org.chem.msu.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1581-1583, October, 2011.
Original article submitted June 28, 2011.
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0009-3122/12/4710-1312©2012 Springer Science+Business Media, Inc.

under nitrous acid oxidation conditions when compared with monophenylated analogs. It was interesting that
treatment of the nitrophenylisoxazoline 3 with one equivalent of HNO2 or of the hydrocarbon 1 with three
equivalents of HNO2 gave, in both cases, a high yield of the 4-(4-nitrophenyl)-3,5-diphenylisoxazole (4).
The experiment with the nitroisoxazoline 3 supports the formation of the nitroisoxazole 4 from
hydrocarbon 1 through the preliminary stage of the isoxazoline 2 nitration.
Hence the corresponding triarylisoxazole derivatives can be synthesized from hydrocarbon 1 depending
upon the ratio of substrate to HNO2.
IR spectra were recorded on a UR-20 instrument in vaseline oil. 1H and 13C NMR spectra were recorded
on a Varian VXR-400 spectrometer using CDCl3 with the residual CHCl3 in the deuterated solvent as internal
standard ( 7.25 and 77.4 ppm respectively). Mass spectra were registered on a Finnigan SSQ 7000 instrument
(GC-MS) using a capillary column (30 m2 mm, DB-1 stationary phase), helium gas carrier (40 ml/min),
temperature programming of 50-300ºC (10 deg/min), and ionization energy 70 eV. Separation of the reaction
mixtures and monitoring of the reaction product purity were carried out on columns or on Silufol or alumina
(Brockmann activity II grade) plates using the solvent system ether–petroleum ether (40-70ºC) (1:3).
Compound 1 was prepared by method [6]; mp 67ºC (EtOH) (mp 66.5-67.5ºC (heptane) [6]).
Reaction of trans-1,2,3-Triphenylcyclopropane (1) with Nitrous Acid (General Method). NaNO2
was added over 30 min to a solution of compound 1 (2.70 g, 0.01 mol) in trifluoroacetic acid (5 ml) and
chloroform (10 ml) at 0ºC. The reaction mixture was held at this temperature for 30 min, poured into water, and
extracted with chloroform. The product was dried over magnesium sulfate, the extract was evaporated, and the
residue was chromatographed on silica gel.
trans-3,4,5-Triphenyl-4,5-dihydroisoxazole (2) was prepared using NaNO2 (0.69 g, 0.01 mol). Yield
2.54 g (85%); mp 138ºC (EtOH) (mp 138-140ºC (heptane) [7]). 1H NMR spectrum, , ppm (J, Hz): 4.74 (1H, d,
J = 5.4, H-4); 5.56 (1H, d, J = 5.4, H-5); 7.26-7.37 (13H, m, H Ar); 7.59 (2H, dd, J = 1.5, J = 7.2, H Ar).
13C NMR spectrum, , ppm: 62.3; 91.7; 125.3; 127.3; 127.5; 127.8; 128.2; 128.5; 128.8; 129.4; 129.8; 139.1;
140.8; 157.5. Mass spectrum, m/z (Irel, %): 299 [M]+ (2), 194 (13), 193 (100), 192 (10), 165 (20), 152(4), 116
(6), 103 (7), 89 (12), 77 (9), 51 (5). Found, %: C 84.17; H 5.58; N 4.21. C21H17NO. Calculated, %: C 84.25;
H 5.72; N 4.68.
trans-3,4,5-Triphenyl-4,5-dihydroisoxazole (2) (2.44 g, 81%) and trans-4-(4-nitrophenyl)-3,5-di-
phenyl-4,5-dihydroisoxazole (3) (0.48 g, 14%) were prepared similarly using NaNO2 (1.38 g, 0.02 mol).
1
Compound 3: mp 197ºC (EtOH). IR spectrum, , cm-1: 1540, 1345 (NO2). H NMR spectrum, , ppm (J, Hz):
4.79 (1H, d, J = 7.5, H-4); 5.72 (1H, d, J = 7.5, H-5); 7.26-7.37 (12H, m, H Ar); 7.59 (2H, d, J = 9.6, H Ar). 13C
NMR spectrum, , ppm: 62.7; 92.8; 123.8; 126.9; 127.5; 128.0; 128.4; 128.8; 129.0; 129.4; 129.7; 130.5; 140.8;
157.5; 166.5. Mass spectrum, m/z (Irel, %): 344 [M]+ (2), 194 (13), 193 (100), 192 (10), 165 (20), 152 (4), 116
(6), 103 (7), 89 (12), 77(9), 51 (5). Found, %: C 73.11; H 4.68; N 8.41. C21H16N2O3. Calculated, %: C 73.24;
H 4.68; N 8.13.
4-(4-Nitrophenyl)-3,5-diphenylisoxazole (4) was prepared using NaNO2 (2.07 g, 0.03 mol). Yield 3.12
g (92%); mp 223ºC (EtOH) (mp 221-222ºC [8]). IR spectrum, , cm-1: 1535, 1340 (NO2). 1H NMR spectrum, ,
ppm (J, Hz): 8.24 (2H, dd, J = 7.1, J = 1.5, H Ar); 7.53 (2H, dd, J = 7.1, J = 1.3, H Ar); 7.45-7.38 (10H, m,
H Ar). 13C NMR spectrum, , ppm: 113.3; 124.2; 127.0; 127.2; 128.2; 128.5; 128.7; 128.9; 129.8; 130.5; 131.3;
137.6; 147.6; 162.0; 166.6. Mass spectrum, m/z (Irel, %): 342 [M]+ (27), 180 (13), 165 (12), 134 (7), 106 (15),
105 (100), 78 (5), 77 (76). Found, %: C 73.43; H 4.38; N 8.01. C21H14N2O3. Calculated, %: C 73.68; H 4.12;
N 8.18.
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