3,5- and 3,6-disubstituted 3,4-dihydroquinazolines

Full text of DOI:10.1134/S1070363216070392

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 7, pp. 1769–1771. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © L.P. Yunnikova, V.V. Esenbaeva, 2016, published in Zhurnal Obshchei Khimii, 2016, Vol. 86, No. 7, pp. 1223–1225.
LETTERS
TO THE EDITOR
3,5- and 3,6-Disubstituted 3,4-Dihydroquinazolines
L. P. Yunnikova and V. V. Esenbaeva
Pryanishnikov Perm State Agricultural Academy, ul. Petropavlovskaya 23, Perm, 614990 Russia
e-mail: yunnikova@yahoo.com
Received November 17, 2015
Keywords: 1,3-dioxolane, dihydroquinazoline, X-ray diffraction analysis
DOI: 10.1134/S1070363216070392
It has previously been shown that the reactions of
para-substituted anilines with formaldehyde in the
presence of hydrochloric [1–3] or oxalic acid [4] lead
to the formation of 6(4’)-substituted 3,4-dihydroquina-
zolines (11–38%). When replacing formaldehyde with
another source of methylene group, metoxychloro-
methane, the reaction with arylamines afforded both
3,4-dihydroquinazolines (25%) and 1,2,3,4-tetrahydro-
quinazolines (48%) [5]. 3,4-Dihydroquinazolines (30–
85%) can be prepared by reacting arylamines with
formaldehyde in a ionic liquid (butylpyridinium 1-
tetrafluoroborate) in the presence of 1-methyl-3-[2-
(sulfooxy)ethyl]-1H-imidazol-3-ylium chloride as
catalyst [6]. 1,3-Dioxolane is known to be used as a
methylene group source in the synthesis of diaryl-
methane derivatives [7], which indicates the possibility
of its use as a synthetic equivalent of formaldehyde or
metoxychloromethane.
In this work we showed a possibility of using 1,3-
dioxolane as a methylene group source in the synthesis
of substituted 3,4-dihydroquinazolines based on para-
and meta-substituted anilines.
The reactions of arylamines 1a–1f with 1,3-di-
oxolane 2 proceeded in benzene in the presence of
trifluoroacetic acid or p-toluenesulfonic acid (pTSA) at
80–85°C to form 3,4-dihydroquinazolines 3a and 4b–4f
(Scheme 1).
According to [7], in the case of m-nitroarylamine
1a having a free para-position the formation of 4,4'-
diamino-3,3'-dinitrodiphenylmethane would be ex-
pected as a result of diarylmethane derivatization.
However, 3-(m-nitrophenyl)-5-nitro-3,4-dihydroquina-
zoline 3a was isolated as the reaction product,
apparently due to the steric hindrances caused by the
presence of nitro moiety in the meta-position. The
Scheme 1.
CF3COOH
or pTSA
N
NH2
N
NO2
O
C6H6
NO2
+
3a
R2
N
O
CF3COOH
R1
1a−1f
N
R1
2
R1
4b−4f
R1 = H, R2 = NO2 (a), R1 = NO2, R2 = H (b), R1 = Br, R2 = H (c), R1 = COOCH3, R2 = H (d), R1 = COOC2H5, R2 = H (e),
R1 = COOC4H9, R2 = H (f).
1769

1770
YUNNIKOVA, ESENBAEVA
(a)
(b)
(a) Crystal structure and (b) molecular packing of compound 3a.
structure compound 3a was confirmed by X-ray
diffraction (XRD) method (see figure).
CH2), 7.26 d (1H, C8H, J = 6.3 Hz), 7.59 d (2H,
C2',6'Н, J = 6.9 Hz), 8.07–8.10 m (3H, C5,7H, CH=N),
8.32 d (2Н, С3',5'Н, J = 6.6 Hz). Mass spectrum, m/z:
299.0776 [М + Н]+.
In conclusion, the proposed non-catalytic method of
synthesizing 3,5- and and 3,6-disubstituted dihydro-
quinazolines involving 1,3-dioxolane as a synthetic
equivalent of formaldehyde allows to reduce the
reaction time and to increase the yield of the target
products.
3-(p-Bromophenyl)-6-bromo-3,4-dihydroqunazoline
(4c). Yield 0.62 g (57%), mp 199–201°С (benzene)
1
(mp 195–200°С [5]). Н NMR spectrum (DMSO-d6),
δ, ppm: 4.90 s (2H, CH2), 6.98 d (2H, C2',6'Н, J = 8.4 Hz),
7.25–7.37 m (4Н, Ar-Н), 7.60 d (2Н, С5,7Н, J = 8.8 Hz),
7.67 s (1H, CH=N). Mass spectrum, m/z: 366.9267
[М + Н]+.
3-(m-Nitrophenyl)-5-nitro-3,4-dihydroqunazoline
(3a). a. A mixture of 4.14 g (30 mmol) of m-nitro-
aniline 1a, 8 mL of benzene, 4.44 g (60 mmol) of 1,3-
dioxolane 2, and 8 mL of trifluoroacetic acid was
heated for 1.5 h at 80–85°C. After cooling the mixture
was diluted with water. The precipitate was separated,
washed twice with water, neutralized with 10%
NH4OH solution to pH 8, and dried. Yield 2.3 g (52%),
3-(p-Carbomethoxyphenyl)-6-carbomethoxy-3,4-
dihydroquinazoline (4d). Yield 1.53 g (47%),
mp 242–245°С (benzene). 1Н NMR spectrum (СDСl3),
δ, ppm: 3.90 s (3Н, NС6Н4COOCH3), 3.92 s (3H,
COOCH3), 4.99 s (2H, CH2), 7.19–7.23 m (3H, C2',6'Н,
C8H), 7.35 s (1Н, С5Н), 7.74 s (1H, CH=N), 7.93 d
(1Н, С7Н, J = 7.8 Hz), 8.12 d (2Н, С3',5'Н, J = 8.4 Hz).
Mass spectrum, m/z: 325.1185 [М + Н]+.
1
yellow crystals, mp 198–200°C (benzene). Н NMR
spectrum (CDCl3), δ, ppm: 5.35 s (2H, CH2), 7.35–
7.69 m (5НAr), 7.93 d (1Н, С6Н, J = 8.4 Hz), 8.09–
8.12 m (2Н, С4'Н, СН=N). Mass spectrum, m/z (Irel,
%): 298 (10.36) [М]+.
3-(p-Carboethoxyphenyl)-6-carboethoxy-3,4-di-
hydroquinazoline (4e). Yield 0.21 g (36%), mp 190°С
b. A mixture of 1.38 g (10 mmol) of m-nitroaniline
1a, 1 mL of benzene, 1.1 g (15 mmol) of 1,3-dioxolane
2, and 2 g of p-toluenesulfonic acid was heated for
1.5 h at 80–85°C. After cooling the mixture was
diluted with water. The precipitate was separated,
washed twice with water, neutralized with 10%
NH4OH solution to pH 8, and dried. Yield 0.4 g (27%).
1
(benzene) (mp 185–188°С [5]). Н NMR spectrum
(DMSO-d6), δ, ppm: 1.37 t (6Н, СН3), 4.35 q (4Н,
ОСН2), 5.11 s (2H, CH2), 7.10–7.22 m (2H, С5,8H), 7.50–
7.53 d (2Н, C2',6'Н, J = 8.4 Hz) 7.80 s (1H, CH=N),
7.86 d (1Н, С7Н, J = 6.6 Hz), 8.04–8.07 d (2Н, С3',5'Н,
J = 8.4 Hz). Mass spectrum, m/z: 353.1498 [М + Н]+.
3-(p-Butoxycarbonylphenyl)-6-butoxycarbonyl-
3,4-dihydroquinazoline (4f). Yield 0.45 g (45%), mp
140°С (dichloromethane). 1Н NMR spectrum (СDСl3),
δ, ppm: 0.98 t (6Н, СН3), 1.41–1.54 m (4Н, СН2), 1.70–
1.80 m (4Н, СН2), 4.28–4.35 m (4Н, ОСН2), 4.99 s
(2H, СН2), 7.19–7.26 m (3H, C2',6'Н, C8H), 7.74 s (1H,
Compounds 4b–4f were prepared similarly by the
method a.
3-(p-Nitrophenyl)-6-nitro-3,4-dihydroquinazoline
(4b). Yield 0.87 g (58%), mp 227–229°С (benzene).
1Н NMR spectrum (DMSO-d6), δ, ppm: 5.16 s (2H,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016

1771
3,5- AND 3,6-DISUBSTITUTED 3,4-DIHYDROQUINAZOLINES
CH=N), 7.93 d (2H, С5,7Н, J = 7.5 Hz), 8.12 d (2Н,
С
AKCNOWLEDGMENTS
3',5'Н). Mass spectrum, m/z: 409.2120 [М + Н]+.
This work was financially supported by the
Ministry of Education and Science of Perm region
(MIG competition, 2013–2015).
1H NMR spectra were obtained on a Mercury 300
instrument (300 MHz), internal reference HMDS.
Mass spectra were recorded on a high resolution mass
spectrometer maXis Impact HD Bruker Daltonik GmbH.
REFERENCES
X-Ray diffraction experiment for compound 3a.
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5849 independent reflections), S 0.785, the ratio of
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group P21/n, the unit cell parameters: a = 14.909(6),
b = 3.8772(11), c = 22.142(7) Å, β = 91.78(3)°, V =
1279.3(7) Å3, dcalc = 1.549 g cm–3, µ = 0.117 mm–1,
Z = 4, λ(MoKα) = 0.71073 Å.
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