10.1002/adsc.201800660
Advanced Synthesis & Catalysis
(1H NMR) spectra were recorded at 500 MHz using a 500
spectrometer. Chemical shifts are reported in delta (δ) units, parts
per million (ppm) downfield from tetramethylsilane or ppm
relative to the center of the singlet at 7.26 ppm for CDCl3 and
2.50 ppm for DMSO-d6. Coupling constants J values are reported
in Hertz (Hz), and the splitting patterns were designated as
follows: s, singlet; d, doublet; t, triplet; m, multiplet; b, broad.
Carbon-13 nuclear magnetic resonance (13C NMR) spectra were
recorded at 125 MHz using a 500 spectrometer. Chemical shifts
are reported in delta (δ) units, ppm relative to the center of the
triplet at 77.0 ppm for CDCl3 and 39.5 ppm for DMSO-d6. 13C
NMR spectra were routinely run with broadband decoupling.
2-Ethyl-6-fluoroquinazolin-4(3H)-one (3ga).[17] White solid,
89% yield (86 mg); mp 227-229 oC; 1H NMR (500 MHz, DMSO-
d6) δ 12.30 (br s, 1H), 7.73 (d, J = 8.9 Hz, 1H), 7.65 (m, 2H),
2.64-2.55 (q, J = 7.5 Hz, 2H), 1.25-1.21 (t, J = 7.5 Hz, 3H); 13C
{1H} NMR (125 MHz, DMSO-d6) δ 161.2, 159.6 (d, JC-F = 244.5
Hz), 157.7, 145.8, 129.5 (d, JC-F = 8.2 Hz), 122.6 (d, JC-F = 24.4
Hz), 121.9 (d, JC-F = 8.7 Hz), 110.2 (d, JC-F = 22.8 Hz), 27.7 , 11.2.
2-Ethyl-7-fluoroquinazolin-4(3H)-one (3ha). White solid, 88%
yield (85 mg); mp 229-231 oC; 1H NMR (500 MHz, DMSO-d6) δ
12.26 (br s, 1H), 8.12 (t, J = 7.6 Hz, 1H), 7.36 (d, J = 10.3 Hz,
1H), 7.30 (d, J = 8.7 Hz, 1H), 2.65-2.59 (q, J = 7.5 Hz, 2H), 1.25-
1.22 (t, J = 7.5 Hz, 3H); 13C {1H} NMR (125 MHz, DMSO-d6) δ
165.6 (d, JC-F = 250.8 Hz), 161.0, 159.9, 151.1 (d, JC-F = 13.5 Hz),
128.7 (d, JC-F = 10.9 Hz), 117.8, 114.3 (d, JC-F = 23.5 Hz), 111.8
(d, JC-F = 21.3 Hz), 27.8, 11.1; HRMS (ESI) m/z calcd for
C10H10FN2O [M+H]+ 193.07717, found 193.07698.
General
procedure
for
catalytic
redox
isomerization/acceptorless dehydrogenation for the synthesis
of quinazolinones from o-aminobenzamides and allylic
alcohols. o-Aminobenzamides (0.5 mmol), allylic alcohols (0.6
mmol, 1.2 equiv), [(p-cymene)RuCl2]2 (3.1 mg, 0.005 mmol, 1
mol %) and THF (1 mL) were added to a microwave vial
containing a stirrer bar. The vial was then placed in a focused,
single-mode microwave synthesizer (Discover CEM, USA) at 130
oC for 3 h (300 W, sealed reaction vessel), and was then cooled to
ambient temperature. The reaction mixture was concentrated
under vacuum and purified by flash column chromatography with
hexanes/ethyl acetate to afford the corresponding products.
6-Chloro-2-ethylquinazolin-4(3H)-one (3ia).[17] White solid,
91% yield (95 mg); mp 218-220 oC; 1H NMR (500 MHz, DMSO-
d6) 8.00 (s, 1H), 7.76 (d, J = 8.7 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H),
2.64-2.60 (q, J = 7.5 Hz, 2H), 1.25-1.21 (t, J = 7.5 Hz, 3H); 13C
{1H} NMR (125 MHz, DMSO-d6) δ 160.8, 158.9, 147.6, 134.2,
130.1, 129.0, 124.6, 122.1, 27.8, 11.1.
7-Chloro-2-ethylquinazolin-4(3H)-one (3ja).[17] White solid,
88% yield (92 mg); mp 205-207 oC; 1H NMR (500 MHz, DMSO-
d6) δ 12.31 (br s, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.65 (d, J = 1.9 Hz,
1H), 7.48 (d, J = 1.8 Hz, 1H), 2.64-2.59 (q, J = 7.5 Hz, 2H), 1.25-
1.20 (t, J = 7.5 Hz, 3H); 13C {1H} NMR (125 MHz, DMSO-d6) δ
161.2, 160.0, 150.0, 138.8, 127.7, 126.1, 125.9, 119.6, 27.9, 11.1.
2-Ethylquinazolin-4(3H)-one (3aa).[12c] White solid, 89% yield
(77 mg); mp 230-232 oC; 1H NMR (500 MHz, DMSO-d6) δ 12.17
(br s, 1H), 8.07 (d, J = 7.8 Hz, 1H), 7.76 (t, J = 7.6 Hz, 1H), 7.60
(d, J = 8.0 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 2.64-2.60 (q, J = 7.5
Hz, 2H), 1.26-1.23 (t, J = 7.5 Hz, 3H); 13C {1H} NMR (125 MHz,
DMSO-d6) δ 161.9, 158.4, 148.8, 134.2, 126.7, 125.9, 125.7,
120.8, 27.9, 11.3.
8-Chloro-2-ethylquinazolin-4(3H)-one (3ka).[17] White solid,
82% yield (86 mg); mp 223-225 oC; 1H NMR (500 MHz, DMSO-
d6) δ 12.40 (br s, 1H), 8.03 (d, J = 7.5 Hz, 1H), 7.91 (d, J = 7.5 Hz,
1H), 7.41 (t, J = 7.6 Hz, 1H), 2.68-2.63 (q, J = 7.3 Hz, 2H),
1.28-1.25 (t, J = 7.5 Hz, 3H); 13C {1H} NMR (125 MHz, DMSO-
d6) δ 161.3, 159.4, 145.3, 134.4, 130.4, 126.2, 124.9, 122.6, 28.1,
11.2.
2-Ethyl-6-methylquinazolin-4(3H)-one (3ba).[15] White solid,
89% yield (84 mg); mp 224-226 oC; 1H NMR (500 MHz, DMSO-
d6) δ 12.06 (br s, 1H), 7.85 (s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.49
(d, J = 8.0 Hz, 1H), 2.62-2.55 (q, J = 7.5 Hz, 2H), 2.39 (s, 3H),
1.25-1.22 (t, J = 7.5 Hz, 3H); 13C {1H} NMR (125 MHz, DMSO-
d6) δ 161.9, 157.5, 147.0, 135.6, 135.6, 126.7, 125.2, 120.6, 27.9,
20.8, 11.4.
6,8-Dichloro-2-ethylquinazolin-4(3H)-one (3la). White solid,
90% yield (109 mg); mp 228-230 oC; 1H NMR (500 MHz,
DMSO-d6) δ 12.56 (br s, 1H), 8.06 (d, J = 2.5 Hz, 1H), 7.97 (d, J
= 2.5 Hz, 1H), 2.67-2.62 (q, J = 7.6 Hz, 2H), 1.27-1.24 (t, J = 7.6
Hz, 3H); 13C {1H} NMR (125 MHz, DMSO-d6) δ 160.3, 159.8,
144.2, 133.7, 131.8, 129.6, 123.9, 123.1, 28.0, 11.0; HRMS (ESI)
m/z calcd for C10H9Cl2N2O [M+H]+ 243.00864, found 243.00854.
2-Ethyl-7-methylquinazolin-4(3H)-one (3ca). White solid, 91%
yield (86 mg); mp 219-221 oC; 1H NMR (500 MHz, DMSO-d6) δ
12.08 (br s, 1H), 7.87 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.35 (d, J
= 3.0 Hz, 1H), 3.85 (s, 3H), 2.62-2.57 (q, J = 7.5 Hz, 2H), 1.24-
1.20 (t, J = 7.5 Hz, 3H); 13C {1H} NMR (125 MHz, DMSO-d6) δ
161.8, 157.5, 146.8, 135.5, 135.5, 126.6, 125.0, 120.6, 55.5, 27.6 ,
11.3; HRMS (ESI) m/z calcd for C11H13N2O [M+H]+189.10224,
found 189.10207.
5-Bromo-2-ethylquinazolin-4(3H)-one (3ma). White solid, 91%
o
yield (115 mg); mp 218-219 C; 1H NMR (500 MHz, DMSO-d6)
δ 12.22 (br s, 1H), 7.65 (m, 1H), 7.57 (m, 2H), 2.61-2.56 (q, J =
7.5 Hz, 2H), 1.24-1.20 (t, J = 7.5 Hz, 3H); 13C {1H} NMR (125
MHz, DMSO-d6) δ 160.0, 158.9, 151.3, 134.2, 132.0, 27.0, 119.9,
118.6, 27.5, 11.0; HRMS (ESI) m/z calcd for C10H10BrN2O
[M+H]+ 252.99710, found 252.99718.
2-Ethyl-6-methoxyquinazolin-4(3H)-one (3da).[16] Light yellow
o
1
solid, 83% yield (85 mg); mp 241-243 C; H NMR (500 MHz,
DMSO-d6) δ 12.10 (br s, 1H), 7.54 (d, J = 8.9 Hz, 1H), 7.46 (d, J
= 3.1 Hz, 2H), 7.47 (d, J = 8.3 Hz, 2H), 2.63-2.58 (q, J = 7.5 Hz,
2H), 2.42 (s, 3H), 1.24-1.20 (t, J = 7.5 Hz, 3H); 13C {1H} NMR
(125 MHz, DMSO-d6) δ 161.7, 157.1, 155.9, 143.4, 128.3, 123.5,
121.5, 105.8, 27.8, 20.8, 11.3.
6-Bromo-2-ethylquinazolin-4(3H)-one (3na).[18] White solid,
88% yield (111 mg); mp 227-229 oC; 1H NMR (500 MHz,
DMSO-d6) δ 12.34 (br s, 1H), 8.14 (d, J = 2.1 Hz, 1H), 7.90 (dd, J
= 8.6 Hz and 2.4 Hz, 2H), 7.54 (d, J = 8.9 Hz, 1H), 2.64-2.59 (q, J
= 7.5 Hz, 2H), 1.25-1.22 (t, J = 7.5 Hz, 3H); 13C {1H} NMR (125
MHz, DMSO-d6) δ 160.7, 159.1, 147.8, 137.0, 129.1, 127.8,
122.4, 118.2, 27.8, 11.1.
2-Ethyl-6,7-dimethoxyquinazolin-4(3H)-one (3ea). White solid,
86% yield (101 mg); mp 232-234 oC; 1H NMR (500 MHz,
DMSO-d6) δ 12.02 (br s, 1H), 7.40 (s, 1H), 7.07 (s, 1H), 3.89 (s,
1H), 3.85 (s, 3H), 2.61-2.56 (q, J = 7.5 Hz, 2H), 1.29-1.20 (t, J =
7.5 Hz, 3H); 13C {1H} NMR (125 MHz, DMSO-d6) δ 161.2,
156.7, 154.5, 148.0, 145.0, 113.6, 107.7, 104.9, 55.9, 55.6, 27.6,
11.3; HRMS (ESI) m/z calcd for C12H15N2O3 [M+H]+ 235.10772,
found 235.10764.
7-Bromo-2-ethylquinazolin-4(3H)-one (3oa).[19] White solid,
83% yield (105 mg); mp 212-214 oC; 1H NMR (500 MHz,
DMSO-d6) δ 12.31 (br s, 1H), 7.97 (d, J = 8.5 Hz, 1H), 7.80 (s,
1H), 7.61 (d, J = 8.5 Hz, 1H), 2.64-2.59 (q, J = 7.5 Hz, 2H), 1.25-
1.21 (t, J = 7.5 Hz, 3H); 13C {1H} NMR (125 MHz, DMSO-d6) δ
161.3, 160.0, 150.0, 128.9, 128.9, 127.7, 119.9, 27.9, 11.1.
2-Ethyl-5-fluoroquinazolin-4(3H)-one (3fa). White solid, 81%
yield (78 mg); mp 208-210 oC; 1H NMR (500 MHz, DMSO-d6) δ
12.20 (br s, 1H), 7.72 (m, 1H), 7.40 (d, J = 8.2 Hz, 1H), 7.17 (d, J
= 8.4 Hz, 1H), 2.62-2.56 (q, J = 7.5 Hz, 2H), 1.24-1.21 (t, J = 7.5
2-Bthyl-7-(trifluoromethyl)quinazolin-4(3H)-one (3pa). White
Hz, 3H); 13C {1H} NMR (125 MHz, DMSO-d6) δ 160.4 (d, JC-F
=
o
1
solid, 88% yield (106 mg); mp 183-185 C; H NMR (500 MHz,
DMSO-d6) δ 12.47 (br s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 7.91 (s,
1H), 7.75 (d, J = 8.3 Hz, 1H), 2.68-2.63 (q, J = 7.5Hz, 2H), 1.27-
1.24 (t, J = 7.5 Hz, 3H); 13C {1H} NMR (125 MHz, DMSO-d6) δ
161.1, 160.3, 148.9, 134.0 (q, J = 32.0 Hz), 127.5, 123.6 (q, J =
312.1 Hz), 159.5, 151.2, 134.7 (d, JC-F = 10.5 Hz), 122.9, 112.3,
112.1, 110.3, 104.9, 55.9, 55.6, 27.7, 11.1; HRMS (ESI) m/z
calcd for C10H10FN2O [M+H]+ 193.07717, found 193.07716.
5
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