Nitration Versus Nitrosation Chemistry of Menthofuran
hydro Woodward-Eastman Lactone, 4). To a solution of 1 (200
tensors were computed within the gauge-including atomic orbitals
(GIAO) ansatz22 at the PBE0/6-311+G(d,p) level. Computed
isotropic shieldings were converted into chemical shifts using as
reference the values obtained at the same level for cyclohexane
mg, 1.33 mmol) in acetonitrile (6 mL) was added DDQ (605 mg,
2.66 mmol, 2 molar equiv). After stirring at rt for 1 h, the reaction
was worked up by filtration over Celite. The filtration cake was
washed with acetonitrile, and the pooled filtrates were evaporated.
The residue was purified by gravity column chromatography on
silica gel (hexane/ethyl acetate 8:2 as the eluant) to afford 4 (97
mg, 44% yield) as a colorless oil.
23
(δ
C
) 27.10, δ
Although large solvent effects on solute geometries and spec-
troscopic parameters are not expected in the relatively apolar CDCl
H
) 1.429, in CDCl
3
).
3
solutions, some test calculations were carried out using the
polarizable continuum model (PCM)24 to simulate the influence of
the solvent. In the PCM approach, the solvent is represented by an
infinite dielectric medium characterized by the relative dielectric
constant of the bulk, and a set of optimized radii (in the present
instance, the UAHF radii)25 are used to build an effective cavity
occupied by the solute within the solvent. In particular, geometry
optimization and computation of NMR parameters were repeated
in the presence of the PCM for the three most stable conformers
of 16, and the resulting averaged chemical shifts were compared
with those obtained in vacuo. However, changes in computed carbon
shifts are smaller than 1.4 ppm, and the correlation coefficient
between experimental and computed carbon shifts is 0.99962
: Oil, IR (liquid film) (νmax, cm-1) 1735, 1661, 1445, 1327,
4
1
1
259, 1212, 1113; H NMR (400 MHz, CDCl
3
) δ 1.14 (d, J ) 6.4
Hz, 3H), 1.48 (m, 1H), 1.87 (br s, 3H), 1.95 (m, 1H), 2.49 (m,
1
4
2
H), 2.59 (m, 1H), 2.71 (dt, J ) 16.5, 5.0 Hz, 1H), 5.60 (d, J )
.1 Hz, 1H); 13C NMR (100 MHz, CDCl
3
) δ 8.4 (CH ), 21.2 (CH ),
1.9 (CH ), 29.8 (CH), 31.0 (CH ), 114.1 (CH), 119.8 (C), 148.2
3
3
2
2
+
(C), 149.2 (C), 171.6 (C); HR ESI+/MS m/z 165.0908 ([M + H] ),
calcd for C10 m/z 165.0916.
13 2
H O
Reaction of 1 with Nitrite. To a solution of 1 (10 mg, 67 µmol)
in dichloromethane (14 mL) was added 0.1 M phosphate buffer
(pH 3.0, 56 mL) (1:4 v/v, with respect to the organic layer),
followed by sodium nitrite (14 mg, 203 µmol), and the biphasic
system was taken under vigorous stirring at rt. After 2 h and 30
min, the organic layer was separated, the aqueous phase was washed
with dichloromethane (3 × 15 mL), and the combined organic
layers were dried over sodium sulfate and taken to dryness. The
residue was analyzed by TLC (eluant cyclohexane/ethyl acetate 1:1)
(versus 0.99965 in vacuo).
Acknowledgment. This work was supported in part by
grants from “Regione Campania legge 5/2005 anno 2006”. We
thank Miss Silvana Corsani of Naples University “Federico II”
for technical assistance, and the Centro Interdipartimentale di
Metodologie Chimico-fisiche of Naples University “Federico
II” for spectral facilities. The assistance of the staff is gratefully
acknowledged.
15
and LC-MS. When required, Na NO
2
was used in the reaction of
1
with nitrite, and the mixture was worked up and analyzed as
above. In other experiments, the reaction of 1 was run as above
but with purging of the biphasic system with argon for at least 30
min prior to the addition of sodium nitrite. In control experiments,
the reaction was carried out under the conditions of the general
procedure without added nitrite.
Isolation of 5,6,7,7a-Tetrahydro-7a-hydroxy-3,6-dimethyl-4H-
benzofuran-2-one (14), 1,4,5,6-Tetrahydro-3,6-dimethyl-2H-in-
dol-2-one (15), and (Z)-(6R,7R,7aS)-4,5,6,7-Tetrahydro-7a-[(6R,-
Supporting Information Available: General experimental
1
13
1
methods; H NMR spectra of compounds 5-7 and 14-16;
C
1
1
1
13
1
13
NMR, H, H COSY, H, C HSQC-DEPT, H, C HMBC, H,
N HMBC spectra of compounds 15 and 16; ROESY and DQF-
15
COSY spectra of compound 16; computational details. This material
is available free of charge via the Internet at http://pubs.acs.org.
7
2
(
aS)-4′,5′,6′,7′-tetrahydro-7a′-hydroxy-3′,6′-dimethyl-2H-indol-
-one-1-oxyl)]-3,6-dimethyl-7-nitro-2H-benzo[b]furan-2-one oxime
16). For preparative purposes, the reaction of 1 with NaNO or
was carried out as described in the general procedure using
g of the starting material. After work up of the reaction mixture,
JO701992R
2
15
Na NO
1
2
(20) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K.
N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;
Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich,
S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A.
D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A.
G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian
03, revision C.02; Gaussian, Inc.: Wallingford, CT, 2003.
the residue (1 g) was fractionated by silica gel column chroma-
tography (3 cm × 85 cm) using petroleum ether/ethyl acetate (40:
60) with 0.5% acetic acid as the eluant (8:2 to 4:6 gradient mixtures)
to give nine fractions. Fractions V, VI, and VII were purified on
preparative TLC using chloroform/ethyl acetate 1:1 as eluant to
give 144 (R
a
0.67, 12 mg, 1% yield, >95% purity), 15 (R
f
f
0.44, 11
0.55, 28 mg, 1% yield,
mg, 1% yield, >95% purity), and 16 (R
f
>
95% purity).
5: [R]25
1
D
3 3
+21.5 (c 0.79, CHCl ); UV λmax (CH OH) 277 nm;
-1
IR (CHCl
3
) (νmax, cm ) 2926, 2869, 1775, 1703, 1558, 1458, 1377,
+
1
346, 1309, 1140; HR ESI+/MS m/z 164.1066 ([M + H] ), calcd
for C10H14NO m/z 164.1075; H, C NMR, and N data, see Table
1 13 15
1
.
(21) For a general introduction on basis sets, see: Foresman, J. B.; Frisch,
1
6: [R]25
64 nm; IR (CHCl
461, 1383, 1156; HR ESI+/MS m/z 422.1921 ([M + H] ), calcd
D
-12.0 (c 0.59, CHCl
3
); UV λmax (CH
3
OH) 249, 285,
A. E. Exploring Chemistry with Electronic Structure Methods, 2nd ed.;
Gaussian Inc.: Pittsburgh, PA, 1996.
(22) Cheeseman, J. R.; Trucks, G. W.; Keith, T. A.; Frisch, J. M. J.
Chem. Phys. 1996, 104, 5497-5509.
(23) SDBSWeb, National Institute of Advanced Industrial Science and
Technology, 2007 (see: http://riodb01.ibase.aist.go.jp/sdbs/,No. 897).
-
1
3
1
3
) (νmax, cm ) 2928, 2853, 1726, 1678, 1558,
+
+
for C20
for C20
Table 1.
H
28
N
3
O
7
m/z 422.1927; m/z 444.1736 ([M + Na] ), calcd
1
13
15
H
27
3 7
N O Na m/z 444.1747; H, C NMR, and N data, see
(
24) (a) Miertus, S.; Scrocco, E.; Tomasi, J. Chem. Phys. 1981, 55, 117-
Compound 16 was treated with diazomethane and analyzed by
TLC and LC-MS. In other experiments, 16 was treated with 2 M
NaOH and the reaction mixture analyzed by LC-MS.
129. (b) Cossi, M.; Scalmani, G.; Rega, N.; Barone, V. J. Chem. Phys.
2002, 117, 43-54. (c) Scalmani, G.; Barone, V.; Kudin, K. N.; Pomelli, C.
S.; Scuseria, G. E.; Frisch, M. J. Theor. Chem. Acc. 2004, 111, 90-100.
(
3
d) Tomasi, J.; Mennucci, B.; Cammi, R. Chem. ReV. 2005, 105, 2999-
Quantum Mechanical Computations. All calculations were
093.
(25) Barone, V.; Cossi, M.; Tomasi, J. J. Chem. Phys. 1997, 107, 3210-
3221.
20
performed with the Gaussian 03 suite. The 6-31+G(d,p) basis
21
set was adopted for geometry optimization, while NMR shielding
J. Org. Chem, Vol. 72, No. 26, 2007 10129