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R. Alonso et al. / Tetrahedron 66 (2010) 4469e4473
3. Conclusions
d
154.6, 149.6, 133.9, 129.9, 129.1, 127.8, 125.2, 124.6, 21.9 ppm. Exact
mass (C9H8N2þH) calculated 145.0759, measured 145.0765.
The cyclization process for [2-(methyleneamino)phenyl]meth-
anone oximes has been studied and this is an excellent method for
the preparation of quinazolines in almost quantitative yields. After
checking the photochemical nature of the reaction, quenching
experiments were used to demonstrate that singlet excited states
4.3.4. 2,4-Diphenylquinazoline17 (2d). Yellow solid. Yield: 90 mg,
53%. Mp: 119e120 ꢃC. 1H NMR:
d
8.71 (d, 2H, J¼9.3 Hz), 8.16 (t, 2H,
J¼8.4 Hz), 7.88e7.93 (m, 3H), 7.56e7.62 (m, 3H), 7.51e7.55 (m, 4H)
ppm. 13C NMR:
168.1, 160.2, 151.9, 138.2, 138.0, 133.5, 130.5, 130.2,
d
undergo the reaction. We computed (CASPT2/6-31G
*
//CASSCF/6-
129.9, 129.2, 128.9, 128.8, 128.7, 128.5, 127.0, 121.7 ppm. Exact mass
31G level, using an active space of 10 electrons in 10 orbitals) the
*
(C20H14N2þH) calculated 283.1230, measured 283.1241.
critical points along the potential energy surface for the singlet
states and the vectors for the CI point responsible for quinazoline
formation. Our experimental and theoretical results are consistent
with a six-electron electrocyclic ring closure mechanism.
4.3.5. 4-Methyl-2-(3-pyridyl)quinazoline (2e). Yellow solid. Yield:
127 mg, 96%. Mp: 105e106 ꢃC. 1H NMR:
d 9.80 (s, 1H), 8.84 (dt, 1H,
J1¼8.1 Hz, J2¼2.1 Hz), 8.71 (d, 1H, J¼3.6 Hz), 8.03e8.07 (m, 2H), 7.86
(t, 1H, J¼5.4 Hz), 7.59 (t, 1H, J¼6.9 Hz), 7.42 (dd, 1H, J1¼3 Hz,
J2¼5.4 Hz), 2.98 (s, 3H) ppm. 13C NMR:
d 168.5, 158.1, 150.9, 150.2,
150.1, 135.7, 133.8, 133.7, 129.1, 127.3, 124.9, 123.2, 123.0, 21.9 ppm.
4. Experimental section
4.1. General
Exact mass (C14H11N3þH) calculated 222.1026, measured 222.1031.
1H and 13C NMR spectra were recorded in CDCl3 with TMS as
internal standard. Melting points are uncorrected. All solvents were
purified by standard procedures. Reagents were of commercial
grades.
4.3.6. 4-Methyl-2-(2-thienyl)quinazoline (2f). Yellow solid. Yield:
99 mg, 73%. Mp: 77e79 ꢃC. 1H NMR:
d
8.13 (d, 1H, J¼3 Hz),
7.94e7.99 (m, 2H), 7.79 (t,1H, J¼6 Hz), 7.46e7.51 (m, 2H), 7.17 (t,1H,
J¼3 Hz), 2.92 (s, 3H) ppm. 13C NMR:
d 168.5, 157.1, 150.2, 144.3,
133.8, 129.7, 129.1, 128.8, 128.3, 126.6, 125.1, 122.9, 21.9 ppm. Exact
mass (C13H10N2SþH) calculated 227.0637, measured 227.0641.
4.2. General procedure for the preparation of [2-
(Methyleneamino)phenyl]methanone Oximes (1)
Acknowledgements
Compound 1a, 1b, 1c, 1e, 1f, and 1g were prepared from
20-aminoacetophenone and 1d was prepared from 2-amino-
benzophenone. A solution of the corresponding ketone (10 mmol),
hydroxylamine hydrochloride (26 mmol), and pyridine (26 mmol)
in ethanol (20 mL) was heated under reflux for 14 h. The solvent
was then removed under vacuum, and the residue extracted with
dichloromethane (50 mL). The organic layer was dried (Na2SO4),
filtered, and evaporated under reduced pressure. The oxime was
then ready to use.
We thank the Spanish MEC (CTQ2007-64197) for financial
support. D.S. is financed by the Ramón y Cajal program from the
MEC. R.A. thanks the Comunidad Autónoma de La Rioja for his
fellowship. A.C. thanks the CSIC for her grant.
Supplementary data
Suplementary data associated with this article can be found in
clude MOL files and InChiKeys of the most important compounds
described in this article.
4.3. Typical procedure for the irradiation of [2-
(methyleneamino)phenyl]methanone oximes (1)
References and notes
The oxime (0.6 mmol) was dissolved in dry acetonitrile (60 mL)
and irradiated at room temperature under an Ar atmosphere
through Pyrex glass with a 400 W medium pressure-mercury lamp
until the oxime was consumed (1e3 h, TLC, hexane/AcOEt, 4:1). The
solvent was removed with a rotary evaporator and the products
were separated by column chromatography (silica gel, hexane/
AcOEt).
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4.3.1. 4-Methyl-2-phenylquinazoline15 (2a). Yellow solid. Yield:
130 mg, 98%. Mp: 89e90 ꢃC. 1H NMR:
d
8.60 (d, 2H, J¼7.5 Hz), 8.01
(d, 1H, J¼9 Hz), 7.91 (d, 1H, J¼9 Hz), 7.74 (t, 1H, J¼7.5 Hz), 7.40e7.52
(m, 4H), 2.89 (s, 3H) ppm. 13C NMR:
168.2, 160.0, 150.2, 138.2,
d
133.4, 130.4, 129.1, 128.6, 128.5, 126.8, 124.9, 122.9, 21.9 ppm. Exact
mass (C15H12N2þH) calculated 221.1073, measured 221.1082.
4.3.2. 4-Methyl-2-pentylquinazoline (2b). Yellow oil. Yield: 100 mg,
78%. 1H NMR:
d
8.06 (d, 1H, J¼8.1 Hz), 7.96 (d, 1H, J¼8.7 Hz), 7.84
(t, 1H, J¼8.1 Hz), 7.57 (t, 1H, J¼8.1 Hz) 3.05 (t, 2H, J¼7.2 Hz), 2.94
(s, 3H), 1.88e1.93 (m, 2H), 1.37e1.45 (m, 4H), 0.91 (t, 3H, J¼6.9 Hz)
ppm. 13C NMR:
d 168.0, 167.0, 149.9, 133.4, 129.0, 126.4, 124.9, 122.4,
40.1, 30.8, 28.8, 22.5, 21.7, 14.0 ppm. Exact mass (C14H18N2þH)
calculated 215.1542, measured 215.1549.
4.3.3. 4-Methylquinazoline16 (2c). Yellow oil. Yield: 26 mg, 30%. 1H
NMR:
d
9.19 (s, 1H), 8.13 (d, 1H, J¼9 Hz), 8.04 (d, 1H, J¼9 Hz), 7.91
(t, 1H, J¼9 Hz), 7.66 (t, 1H, J¼9 Hz), 2.98 (s, 3H) ppm. 13C NMR: