Chemical transformations of mackinazolinone and its derivativesa

Article abstract of DOI:10.1007/s10600-012-0331-0

The thioanalog of mackinazolinone (2,3,4,10-tetrahydro-1H-pyrido[2,1-b] quinazolin-10-one) was synthesized for the first time by reacting it with P2S5. The thioanalog was reacted with aromatic aldehydes and Vilsmeier- Haack reagent (DMF + POCl3) to produce 4-arylidene- and - hydroxymethylidenemackinazolinthiones, respectively. The reactions of 4-hydroxymethylidenemackinazolinone with isomeric aminophenols and aminobenzoic acids and of hydroxymethylidenemackinazolinthione with thionylchloride were studied. Subsequent reaction of the obtained 4-chloromethylidene derivative with sodium hydroselenide was synthesized a new Se-containing derivative of mackinazolinone. It was shown that 4-formylmackinazolinthione existed in the enol form whereas 4-formylmackinazolinone existed as the enaminoaldehyde tautomer.

Full text of DOI:10.1007/s10600-012-0331-0

Chemistry of Natural Compounds, Vol. 48, No. 4, September, 2012 [Russian original No. 4, July–August, 2012]
CHEMICAL TRANSFORMATIONS OF MACKINAZOLINONE
a
AND ITS DERIVATIVES
1
1
1*
A. O. Nasrullaev, Zh. E. Turdibaev, B. Zh. Elmuradov,
UDC 547.944/945+547.856
2
2
1
A. Yili, H. A. Aisa, , and Kh. M. Shakhidoyatov
The thioanalog of mackinazolinone (2,3,4,10-tetrahydro-1H-pyrido[2,1-b]quinazolin-10-one) was synthesized
for the first time by reacting it with P S . The thioanalog was reacted with aromatic aldehydes and Vilsmeier–
2 5
Haack reagent (DMF + POCl ) to produce 4-arylidene- and –hydroxymethylidenemackinazolinthiones,
3
respectively. The reactions of 4-hydroxymethylidenemackinazolinone with isomeric aminophenols and
aminobenzoic acids and of hydroxymethylidenemackinazolinthione with thionylchloride were studied.
Subsequent reaction of the obtained 4-chloromethylidene derivative with sodium hydroselenide was
synthesized a new Se-containing derivative of mackinazolinone. It was shown that 4-formylmackinazolinthione
existed in the enol form whereas 4-formylmackinazolinone existed as the enaminoaldehyde tautomer.
Keywords: mackinazolinone, mackinazolinthione, nucleophilic substitution, electrophilic addition.
Derivatives of tricyclic quinazolines, quinazolin-4-ones, and their homologs are used in medical practice as
pharmacologically active compounds [1–4].
The alkaloid mackinazolinone (2,3,4,10-tetrahydro-1H-pyrido[2,1-b]quinazolin-10-one, 1) was isolated from a species
of Mackinlaya [5]. It was synthesized [2, 5] and its reactions with acid chlorides [6, 7], a formylating agent [7, 8], and
aromatic and heterocyclic aldehydes [9] were studied. The thioanalog of 1 has not been reported although there is information
on the synthesis of thiodeoxyvasicinone (1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-4-thione) [10].
Herein we present results on the chemical transformation of 1 and mackinazolinthione (2). The latter was prepared
by the reaction of 1 with P S according to the literature method [10] that was developed for transformation of deoxyvasicinone
2 5
into thiodeoxyvasicinone.
The reaction of 2 with aromatic aldehydes in glacial HOAc occurred at the ꢀ-C atom of 2 and formed 4-arylidene-2
(3a–d). Benzaldehyde, 4-dimethylamino-, and 4-nitrobenzaldehyde (a–c) and furfurol (d) were used as the aldehydes. The
condensation proceeded upon heating of equimolar amounts of the starting materials in glacial AcOH for 2–8 h. The
corresponding 4-arylidene(furfurylidene-2ꢁ)-mackinazolinthiones (3a–d) were synthesized.
Compound 2 was formylated using Vilsmeier–Haack reagent (DMF + POCl ) under the conditions for formylation
3
of 1 [11]. This formed 4-hydroxymethylidenemackinazolinthione (4). The structures of the compounds were studied using
physical analytical methods (IR and PMR spectra) and showed that the enol form was stable. Thus, ꢂ
stretching vibrations
C=S
–1
in the IR spectrum appeared at 1283 cm ; ꢂ
, 1563; ꢂ
, 1488; and ꢂ , 3435. The PMR spectrum of 4 in CDCl
C=N
C–N OH 3
exhibited a 1H singlet for the OH at 14.7 ppm. Methylene protons in the 1-position had chemical shift (CS) 3.83 ppm (triplet);
in the 3-position, 2.48 (triplet); in the 2-position, 1.91 (multiplet). Olefinic proton =CH had CS 8.76 ppm (singlet); aromatic
protons of the benzene ring, 7.11–8.03.
______
a
th
Materials presented at the 9 International Symposium on the Chemistry of Natural Compounds (SCNC, People’s Republic
of China, Urumqi, Oct. 16–19, 2011).
1) S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences, Republic of Uzbekistan,
Tashkent; fax (99871) 120 64 75, e-mail: burkhon@rambler.ru; 2) Key Laboratory of Xinjiang Indigenous Medicinal Plants
Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011,
P. R. China. Translated from Khimiya Prirodnykh Soedinenii, No. 4, July–August, 2012, pp. 573–577. Original article
submitted April 4, 2012.
©
638
0009-3130/12/4804-0638 2012 Springer Science+Business Media, Inc.

S
S
S
NaHSe
SOCl
2
SOCl
CHCl
2
N
N
N
.
6 (5 HCl)
3
N
N
N
CH SeH
CH Cl
CH OH
5
7
4
POCl + DMF
3
O
O
N
N
1
S
9
POCl + DMF
3
P S
2 5
m-xylene
10
1
N
N
3
7
N
H
N
O
5
C
8
2
H
ArCHO AcOH
O
O
N
N
S
Ar-NH
N
2
N
N
N
CH OH
CH NHAr
CH Ar
9a - g
8a
3a - d
Ar = C H (3a), C H -N(CH ) -4 (3b), C H -NO -4 (3c), furyl-2 (3d)
6
5
6
4
3 2
6
4
2
C H -OH-2 (9a), C H -OH-3 (9b), C H -OH-4 (9c), C H -COOH-2 (9d),
6
4
6
4
6
4
6 4
C H -COOH-3 (9e), C H -COOH-4 (9f), C H -COOH-2-Br-5 (9g)
6
4
6
4
6 3
Compound 4 underwent nucleophilic substitution of the OH by Cl upon reacting with an excess of thionylchloride
with heating on a water bath to form 4-chloromethylidenemackinazolinthione (5) in 98% yield. However, it was unstable and
decomposed with release of HCl upon standing. We reacted equimolar amounts of 4 and SOCl in anhydrous CHCl in order
2
3
to prepare a stable form of this compound. This produced 4-chloromethylidenemackinazolinthione hydrochloride (6) in
78.5% yield.
Compound 5 reacted rapidly with sodium hydroselenide to afford 4-hydroselenylmethylidenemackinazolinthione
(7). We demonstrated that similar compounds could be synthesized using 3-chloromethylidenedeoxyvasicinone as an example
[12].
It was observed earlier [2] that the reaction of 1 with Vilsmeier–Haack reagent (POCl :DMF) formed exclusively
3
4-formyl derivative 8. Furthermore, 8 can exist in enol form 8a, which reacts readily with nucleophilic reagents. We studied
the reactions of the nucleophiles o-, m-, and p-aminophenols (a–c); o-, m-, and p-aminobenzoic acids (d–f); and 5-bromo-
o-aminobenzoic acid (g) with 8a. The reactions were carried out in refluxing MeOH for 3 h. Nucleophilic substitution
products 9a–g were obtained. The yields of products obtained from condensation of 8 with nucleophilic reagents containing
an electron-donating (OH) group (a–c) were slightly greater (74–80%) than those involving an electron-acceptor group (COOH)
(d–f) (67–70%). The yield was even lower (38.6%) for 5-bromo-o-aminobenzoic acid (g). This was due to the fact that the
nucleophilicity of the amine in the isomeric aminobenzoic acids decreased under the influence of the electron-acceptor
substituents.
The structures of 4–7 were confirmed by IR and PMR spectral data. Their IR spectra showed ꢂ
stretching vibrations
C=S
–1
in the range 1278–1284 cm ; ꢂ
, 1552–1584; and ꢂ
, 1450–1471. CSs in PMR spectra were 4.13–4.6 and 3.90–
C=N
C–N
4.13 ppm (triplets) for methylene protons in the 1-position in 3a–d and 9a–g; 2.78–2.90 and 2.33–2.73 (triplet) for those in the
3-position; and 1.78–2.0 (multiplet) for protons in the 2-position. The N(CH ) resonance in 3b gave a 6H singlet at 2.96 ppm.
3 2
The aromatic protons appeared at 6.70–8.74 ppm.
EXPERIMENTAL
Mass spectra were recorded on an MS-30 (Kratos) instrument; IR spectra, in mineral oil on a System 2000 IR-Fourier
spectrometer; PMR spectra, in CDCl (2, 3a–c, 4), CD COOD (7, 9e), DMSO-d (9a), and TFA + CD COOD (3d, 9g, 9f) on
3
3
6
3
a Unity 400+ instrument (operating frequency 400 MHz, TMS internal standard, ꢃ-scale). The purity of products and course
/
of reactions were monitored by TLC on Sorbfil (Russia) and Whatman UV-254 (Germany) plates using CHCl :MeOH (5:1,
3
system A; 10:1, system B) and C H :MeOH (5:1, system C).
6
6
639

Mackinazolinone (1) was synthesized by the literature method [13]; mackinazolinthione (2), by the previous method
[10] with several changes.
A mixture of 1 (7.2 g, 0.036 mol) and P S (8.3 g, 0.037 mol) in m-xylene (40 mL) was refluxed and stirred for 3 h
2 5
and cooled to room temperature. The resulting precipitate was filtered off, worked up with NaOH (80 mL, 10%), left for 1 h,
filtered off, washed with H O until neutral, and dried. Recrystallization from hexane afforded 2 (5.45 g, 70%), C H N S,
2
12 12 2
–1
mp 118–120°C, R 0.88 (system C). IR spectrum (ꢂ, cm ): 1584 (ꢂ
), 1471 (ꢂ
), 1270 (ꢂ ).
f
C=N
C–N C=S
PMR spectrum (ꢃ, ppm, J/Hz): 8.73 (1H, dd, J = 8.2, 1.6, H-9), 7.7 (1H, t, J = 8.2, 1.6, H-7), 7.5 (1H, d, J = 8.2, H-6),
7.4 (1H, t, J = 8.2, H-8), 4.55 (2H, t, J = 6.2, H-1), 3.0 (2H, t, J = 6.9, H-4), 2.0 (2H, m, H-2), 1.92 (2H, m, H-3).
4-Benzylidenemackinazolinthione (3a). Compound 2 (0.218 g, 1 mmol) was dissolved in glacial AcOH (4 mL),
3
treated with benzaldehyde (0.110 mL, 0.116 g, 1.1 mmol, ꢄ = 1.0498 g/cm ) and refluxed for 2–8 h. The resulting precipitate
was filtered off, washed with H O, and dried. Recrystallization from cyclohexane afforded 3a (0.198 g, 65%), C H N S,
2
19 16 2
–1
mp 168°C, R 0.86 (system C). IR spectrum (ꢂ, cm ): 1567 (ꢂ
), 1491 (ꢂ
), 1268 (ꢂ ).
f
C=N
C–N C=S
PMR spectrum (ꢃ, ppm, J/Hz): 8.70 (1H, d, J = 7.7, H-9), 8.1 (1H, t, J = 2.0, =CH), 7.65–7.68 (2H, m, H-6,7), 7.34–
7.42 (5H, m, H ), 7.28 (1H, td, J = 7.7, 1.6, H-8), 4.6 (2H, t, J = 5.7, H-1), 2.9 (2H, td, J = 6.6, 2.0, H-3), 2.0 (2H, m, H-2).
Ph
4-(4-Dimethylaminobenzylidene)-mackinazolinthione (3b). By analogy with the above, 2 (0.317 g, 1.5 mmol)
and 4-dimethylaminobenzaldehyde (0.224 g, 1.65 mmol) synthesized 3b (0.312 g, 60%), mp 184°C (cyclohexane), R 0.87
f
–1
(system C). IR spectrum (ꢂ, cm ); 1566 (ꢂ
), 1470 (ꢂ
), 1267 (ꢂ ).
C=N
C–N C=S
PMR spectrum (ꢃ, ppm, J/Hz): 8.72 (1H, dd, J = 8.2, 1.1, H-9), 8.0 (1H, t, J = 2.0, =CH), 7.66 (2H, d, J = 7.1, H-2ꢁ,6ꢁ),
7.38–7.40 (3H, m, H-6,7,8), 6.7 (2H, d, J = 7.1, H-3ꢁ,5ꢁ), 4.6 (2H, t, J = 5.7, H-1), 2.96 [6H, s, N(CH ) ], 2.9 (2H, td, J = 6.0,
3 2
2.0, H-3), 2.0 (2H, m, H-2).
4-(4-Nitrobenzylidene)-mackinazolinthione (3c). By analogy with the above, 2 (0.432 g, 2 mmol) and
4-nitrobenzaldehyde (0.332 g, 2.2 mmol) afforded 3c (0.517 g, 74%), mp 209–210°C (cyclohexane), R 0.88 (system C).
f
–1
IR spectrum (ꢂ, cm ): 1568 (ꢂ
), 1509 (ꢂ
), 1469 (ꢂ
), 1223 (ꢂ ).
C=N
NO
C–N C=S
2
PMR spectrum (ꢃ, ppm, J/Hz): 8.74 (1H, d, J = 8.2, H-9), 8.23 (2H, d, J = 8.8, H-3ꢁ,5ꢁ), 8.2 (1H, s, =CH), 7.66–7.74
(2H, m, H-6,7), 7.56 (2H, d, J = 8.8, H-2ꢁ,6ꢁ), 7.46 (1H, t, J = 8.2, H-8), 4.62 (1H, t, J = 6.0, H-1a), 4.13 (1H, t, J = 6.0, H-1b),
2.90 (2H, t, J = 6.0, H-3), 1.98–2.11 (2H, m, H-2).
4-(Furfurylidene-2)-mackinazolinthione (3d). By analogy with the above, 2 (0.432 g, 2 mmol) and furfurol
3
(0.18 mL, 0.21 g, 2.2 mmol, ꢄ = 1.1598 g/cm ) synthesized 3d (0.39 g, 68%), mp 170°C (cyclohexane), R 0.88 (system C).
f
–1
IR spectrum (ꢂ, cm ): 1569 (ꢂ
), 1469 (ꢂ
), 1272 (ꢂ ).
C=N
C–N C=S
PMR spectrum (ꢃ, ppm, J/Hz): 8.28 (1H, d, J = 8.2, H-9), 7.5 (1H, t, J = 8.2, H-7), 7.39 (1H, d, J = 1.7, H-5ꢁ), 7.30
(1H, t, J = 1.7, =CH), 7.23–7.29 (2H, m, H-6,8), 6.68 (1H, d, J = 3.4, H-3ꢁ), 6.3 (1H, dd, J = 3.4, 1.7, H-4ꢁ), 4.36 (2H, t, J = 5.5,
H-1), 2.78 (2H, td, J = 6.8, 1.7, H-3), 1.85 (2H, m, H-2).
4-Hydroxymethylidenemackinazolinthione (4) was prepared by the literature method [11] with several changes.
Freshly distilled anhydrous DMF (1.93 g, 0.027 mol) was cooled on an ice bath, stirred vigorously by a mechanical stirrer,
treated dropwise with POCl (1.54 g, 0.01 mol) and in portions with 2 (1 g, 0.046 mol), stirred for 2 h at room temperature, left
3
overnight, heated for 2 h on a water bath (95–98°C), cooled, decomposed with ice (10 g), and neutralized with NH OH
4
solution (10%) until weakly basic (pH 8). The resulting yellow solid was filtered off, washed with H O (3–4ꢅ), and dried to
2
–1
afford 4 (0.88 g, 78%), mp 206–208°C (acetone), R 0.74 (system C). IR spectrum (ꢂ, cm ): 3435 (ꢂ ), 1563 (ꢂ
),
f
OH
C=N
1488 (ꢂ
), 1283 (ꢂ ).
C–N
C=S
PMR spectrum (ꢃ, ppm, J/Hz): 14.67 (1H, s, OH), 8.54 (1H, s, =CH), 7.95 (1H, dd, J = 7.9, 1.7, H-9), 7.57 (1H, td,
J = 8.3, 1.7, H-7), 7.2 (1H, d, J = 8.3, H-6), 7.16 (1H, td, J = 7.9, 0.8, H-8), 3.94 (2H, t, J = 5.8, H-1), 2.48 (2H, t, J = 6.2,
H-3), 1.91 (2H, m, H-2).
4-Chloromethylidenemackinazolinthione (5). Compound 3 (0.6 g, 2.44 mmol) was heated, treated with freshly
3
distilled SOCl (4 mL, 56.8 mmol, ꢄ = 1.66 g/cm ), heated on a water bath at 70–75°C for 1.5–2 h, cooled, and decomposed
2
with distilled H O (100 mL). The resulting precipitate was filtered off, washed with H O, and dried to afford 5 (0.63 g, 98%),
2
2
–1
mp 120°C (dec.), R 0.96 (system C). IR spectrum (ꢂ, cm ): 1563 (ꢂ
), 1474 (ꢂ
), 1278 (ꢂ ), 771 (ꢂ
).
f
C=N
C–N
C=S
C–Cl
4-Chloromethylidenemackinazolinthione Hydrochloride (6). A solution of 3 (1 g, 4.1 mmol) in anhydrous CHCl
3
3
(20 mL) was treated dropwise with SOCl (0.4 mL, 5.6 mmol, ꢄ = 1.66 g/cm ), and stirred for 30 min at room temperature.
2
The resulting crystals were filtered off, washed with CHCl , and dried to afford 6 (0.96 g, 78.5%), mp 200–202°C, R 0.83
3
f
–1
(system C). IR spectrum (ꢂ, cm ): 1567 (ꢂ
), 1484 (ꢂ
), 1284 (ꢂ ), 757 (ꢂ
).
C=N
C–N
C=S
C–Cl
640

4-Hydroselenylmethylidenemackinazolinthione (7). Amixture of selenium (0.26 g, 3.3 mmol) in deaerated distilled
H O (25 mL) was constantly purged with N , treated in portions with NaBH (0.25 g, 6.6 mmol) over 30 min, stirred for
2
2
4
another 15–20 min, and heated to 40–45°C for 1 h. During this time the mixture became brownish-red. The mixture was
cooled under a stream of N , treated with 5 (0.9 g, 3 mmol), stirred for 1 h at room temperature and just as long at 95–98°C, and
2
cooled to room temperature. The resulting precipitate was filtered off. The filtrate was acidified with conc. AcOH until the
pH was 1–2. The resulting red crystals were filtered off, washed with H O until neutral, and dried to afford 7 (0.56 g, 52%),
2
–1
mp 112–114°C (cyclohexane), R 0.89 (system C). IR spectrum (ꢂ, cm ): 2795 (ꢂ
), 1563 (ꢂ
), 1474 (ꢂ
),
f
Se–H
C=N
C–N
1283 (ꢂ ).
C=S
PMR spectrum (ꢃ, ppm, J/Hz): 8.77 (1H, t, J = 1.9, =CH), 8.1 (1H, dd, J = 8.0, 1.6, H-9), 7.99 (1H, d, J = 8.0, H-6),
7.77 (1H, td, J = 8.0, 1.6, H-7), 7.5 (1H, td, J = 8.0, 1.3, H-8), 4.13 (2H, t, J = 6.4, H-1), 2.73 (2H, td, J = 6.8, 1.9, H-3), 1.98
(2H, m, H-2).
4-Formylmackinazolinone (8) was prepared by the literature method [11].
4-(o-Hydroxyphenylamino)methylidenemackinazolinone (9a). Compound 8 (0.228 g, 1 mmol) was dissolved in
MeOH (10 mL), treated with o-aminophenol (0.109 g, 1 mmol), and refluxed for 3 h. When the reaction was finished, the
solvent was vacuum distilled. The solid was recrystallized from MeOH to afford 9a (0.248 g, 78%), C H N O , mp 224–
19 17
3 2
+
+
+
226°C, R 0.63 (system A). Mass spectrum (m/z, %): 319 (100) [M] , 302 (16) [M – OH] , 226 (8.4) [M – C H – OH] ,
f
6 4
+
–1
199 (77) [M – CH=N – C H – OH] , 185 (20), 145 (5), 119 (29). IR spectrum (ꢂ, cm ): 3273 (ꢂ ), 2934 (ꢂ ), 1639
6
4
OH
NH
(ꢂ
), 1523 (ꢂ
), 1474 (ꢂ
).
C=O
C=N
C–N
PMR spectrum (ꢃ, ppm, J/Hz): 10.14 (1H, s, OH), 7.98 (1H, dd, J = 8.0, 1.5, H-9), 7.68 (1H, td, J = 7.1, 1.5, H-7), 7.63
(1H, d, J = 12.2, =CH), 7.55 (1H, d, J = 7.8, H-3ꢁ), 7.27 (2H, m, H-8,6ꢁ), 6.83 (1H, dd, J = 7.1, 2.1, H-6), 6.73 (2H, m,
H-4ꢁ,5ꢁ), 3.90 (2H, t, J = 5.6, H-1), 2.56 (2H, t, J = 5.6, H-3), 1.88 (2H, m, H-2).
4-(m-Hydroxyphenylamino)methylidenemackinazolinone (9b). By analogy to the above, 8 (0.228 g, 1 mmol) and
m-aminophenol (0.109 g, 1 mmol) afforded 9b (0.236 g, 74%), C H N O , mp 180–182°C (MeOH), R 0.48 (system A).
19 17
3
2
f
+
+
+
Mass spectrum (m/z, %): 319 (100) [M] , 226 (16) [M – C H – OH] , 199 (26) [M – CH=N – C H – OH] , 184 (9.1),
6
4
6 4
), 1473 (ꢂ
–1
146 (7), 119 (15.4). IR spectrum (ꢂ, cm ): 3367 (ꢂ ), 3014 (ꢂ ), 1647 (ꢂ
), 1518 (ꢂ
).
OH
NH
C=O
C=N
C–N
4-(p-Hydroxyphenylamino)methylidenemackinazolinone (9c). By analogy to the above, 8 (0.228 g, 1 mmol) and
p-aminophenol (0.109 g, 1 mmol) afforded 9c (0.255 g, 80%), C H N O , mp 240–242°C (MeOH), R 0.56 (system A).
19 17
3
2
f
+
+
+
Mass spectrum (m/z, %): 319 (100) [M] , 302 (7) [M – OH] , 226 (8.4) [M – C H – OH] , 199 (16.8), 184 (6.3), 119 (14).
6
4
–1
IR spectrum (ꢂ, cm ): 3231 (ꢂ ), 2939 (ꢂ ), 1628 (ꢂ
), 1523 (ꢂ
), 1474 (ꢂ
).
OH
NH
C=O
C=N
C–N
4-(o-Hydroxycarbonylphenylamino)methylidenemackinazolinone (9d). Compound 8 (0.228 g, 1 mmol) was
dissolved in MeOH (10 mL), treated with o-aminobenzoic acid (0.137 g, 1 mmol), and refluxed for 3 h. When the reaction was
finished, the solvent was vacuum distilled. The solid was recrystallized from MeOH to afford 9d (0.244 g, 70%),
+
+
C H N O , mp 178–180°C, R 0.53 (system A). Mass spectrum (m/z, %): 347 (100) [M] , 302 (54) [M – COOH] ,
20 17
3
3
f
+
+
+
226 (12.6) [M – C H – COOH] , 211 (8.4) [M – NH – C H – COOH] , 200 (24.5), 198 (7) [M – CHNH – C H – COOH] ,
184 (17.5), 186 (13), 143 (5), 119 (52.5). IR spectrum (ꢂ, cm ): 3413 (ꢂ ), 3215 (ꢂ ), 1681 (ꢂ
6
4
6
4
6 4
), 1635 (ꢂ
–1
),
OH
NH
O–C=O
C=O
1533 (ꢂ
), 1472 (ꢂ
).
C=N
C–N
4-(m-Hydroxycarbonylphenylamino)methylidenemackinazolinone (9e). By analogy with the above, 8 (0.228 g,
1 mmol) and m-aminobenzoic acid (0.137 g, 1 mmol) afforded 9e (0.232 g, 67%), C H N O , mp 276–278°C (MeOH),
20 17
+
3 3
+
+
R 0.58 (system A). Mass spectrum (m/z, %): 347 (100) [M] , 330 (41) [M – OH] , 302 (4.2) [M – COOH] , 226 (17.5)
f
+
+
+
[M – C H – COOH] , 211 (8.4) [M – NH – C H – COOH] , 199 (16.8), 198 (8.4) [M – CHNH – C H – COOH] , 185 (7.7),
6
4
6
4
6 4
–1
144 (3.5), 119 (10.5). IR spectrum (ꢂ, cm ): 3450 (ꢂ ), 2924 (ꢂ ), 1686 (ꢂ
), 1646 (ꢂ
), 1527 (ꢂ
), 1474 (ꢂ
).
OH
NH
O–C=O-
C=O
C=N
C–N
PMR spectrum (ꢃ, ppm, J/Hz): 8.15 (1H, d, J = 13.7, NH), 8.02 (1H, d, J = 13.7, =CH), 7.87 (1H, d, J = 8.1, H-9), 7.69
(1H, s, H-2ꢁ), 7.63 (1H, d, J = 7.2, H-6), 7.5 (1H, t, J = 7.5, H-8), 7.12-7.20 (4H, m, H-7,4ꢁ,5ꢁ,6ꢁ), 3.9 (2H, t, J = 6.0, H-1), 2.33
(2H, t, J = 6.0, H-3), 1.78 (2H, m, H-2).
4-(p-Hydroxycarbonylphenylamino)methylidenemackinazolinone (9f). By analogy with the above, 8 (0.228 g,
1 mmol) and p-aminobenzoic acid (0.137 g, 1 mmol) afforded 9f (0.235 g, 68%), C H N O , mp 296–298°C (MeOH),
20 17
3 3
+
+
+
R 0.46 (system A). Mass spectrum (m/z, %): 347 (100) [M] , 330 (39.8) [M – OH] , 302 (4.9) [M – COOH] , 226 (17.5)
[M – C H – COOH] , 211 (9.1) [M – NH – C H – COOH] , 199 (17.5), 198 (7.7) [M – CHNH – C H – COOH] , 185 (8.4),
f
+
+
+
6
4
6
4
6 4
–1
144 (2.8), 119 (11.2). IR spectrum (ꢂ, cm ): 3422 (ꢂ ), 3053 (ꢂ ), 1697 (ꢂ
), 1636 (ꢂ
), 1521 (ꢂ
), 1476 (ꢂ
).
OH
NH
O–C=O-
C=O
C=N
C–N
641

PMR spectrum (ꢃ, ppm, J/Hz): 10.89 (1H, s, OH), 8.1 (1H, d, J = 13.6, =CH), 8.05 (1H, d, J = 13.6, NH), 7.89 (1H,
d, J = 8.1, H-9), 7.78 (1H, d, J = 8.4, H-3ꢁ,5ꢁ), 7.52 (1H, t, J = 8.1, H-7), 7.21 (1H, t, J = 8.1, H-8), 7.17 (1H, d, J = 8.1, H-6),
6.96 (2H, d, J = 8.4, H-2ꢁ,6ꢁ), 3.91 (2H, t, J = 5.8, H-1), 2.35 (2H, t, J = 6.5, H-3), 1.82 (2H, m, H-2).
4-(5-Bromo-2-hydroxycarbonylphenylamino)methylidenemackinazolinone (9g). By analogy with the above, 8
(0.228 g, 1 mmol) and 5-bromo-o-aminobenzoic acid (0.216 g, 1 mmol) afforded 9g (0.164 g, 38.6%), C H BrN O ,
20 16
+
3 3
+
mp 274–276°C (aq. DMF), R 0.61 (system C). Mass spectrum (m/z, %): 425/427 (64) [M] , 408 (4.9) [M – OH] , 380/382
f
+
(100) [M – COOH] , 301 (5.6), 226 (31.5), 211 (20.3), 198 (32), 183 (21), 145 (12.6), 120 (31).
PMR spectrum (ꢃ, ppm, J/Hz): 8.2 (1H, d, J = 13.1, =CH), 7.98 (1H, d, J = 2.2, H-6ꢁ), 7.89 (1H, d, J = 8.0, H-9), 7.53
(1H, t, J = 7.5, H-7), 7.42 (1H, dd, J = 9.0, 2.2, H-4ꢁ), 7.23 (1H, d, J = 7.5, H-6), 7.18 (1H, t, J = 8.0, H-8), 7.03 (1H, d, J = 9.0,
H-3ꢁ), 3.92 (2H, t, J = 5.2, H-1), 2.35 (2H, t, J = 5.2, H-3), 1.86 (2H, m, H-2).
ACKNOWLEDGMENT
The work was supported financially by the RU TsNT (Project No. FA-F3-T047).
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