Synthesis of 8-amino- and 8-acetyl(benzoyl) aminomackinazolinones and their condensation with aldehydes

Article abstract of DOI:10.1007/s10600-013-0587-z

Methods for preparing of 8-nitro- and 8-aminomackinazolinones were improved. 8-Acetyl(benzoyl)aminomackinazolinones reacted smoothly with aromatic aldehydes and furfurol in glacial acetic acid to give the corresponding 4-arylidene-substituted derivatives. Reaction of 8-aminomackinazolinone with aromatic aldehydes in glacial acetic acid was accompanied by acetylation of the amine and gave 8-acetylamino-4-arylidenemackinazolinones. Reaction of 8-aminomackinazolinone and p-nitrobenzaldehyde in propionic acid produced 8-[(4' -nitrobenzylidene)amino]-4-(4'-nitrobenzylidene)mackinazolinone. In contrast, the reaction in Py occurred selectively at the amine to form the corresponding Schiff base 8-[(4'-nitrobenzylidene)amino]mackinazolinone.

Full text of DOI:10.1007/s10600-013-0587-z

Chemistry of Natural Compounds, Vol. 49, No. 2, May, 2013 [Russian original No. 2, March–April, 2013]
SYNTHESIS OF 8-AMINO- AND 8-ACETYL(BENZOYL)
AMINOMACKINAZOLINONES AND THEIR
CONDENSATION WITH ALDEHYDES
*
A. Sh. Abdurazakov, B. Zh. Elmuradov, I. S. Ortikov,
UDC 547.944/945+547.856
M. G. Levkovich, and Kh. M. Shakhidoyatov
Methods for preparing of 8-nitro- and 8-aminomackinazolinones were improved.
8-Acetyl(benzoyl)aminomackinazolinones reacted smoothly with aromatic aldehydes and furfurol in glacial
acetic acid to give the corresponding 4-arylidene-substituted derivatives. Reaction of
8-aminomackinazolinone with aromatic aldehydes in glacial acetic acid was accompanied by acetylation of
the amine and gave 8-acetylamino-4-arylidenemackinazolinones. Reaction of 8-aminomackinazolinone
and p-nitrobenzaldehyde in propionic acid produced 8-[(4ꢀ-nitrobenzylidene)amino]-4-
(4ꢀꢀ-nitrobenzylidene)mackinazolinone. In contrast, the reaction in Py occurred selectively at the amine to
form the corresponding Schiff base 8-[(4ꢀ-nitrobenzylidene)amino]mackinazolinone.
Keywords: mackinazolinone, aldehydes, condensation, 4-arylidene derivatives.
Quinazoline alkaloids and their synthetic analogs are of definite theoretical and practical interest. 2,3,4,10-Tetrahydro-
1H-pyrido[2,1-b]quinazolin-10-one (the alkaloid mackinazolinone, 1, R = H) was first isolated from the plant Mackinlaya
subulata Philipson [1]. The synthesis [2–5] and chemical transformations [6–10] of this alkaloid and its derivatives are rather
well studied.
It was shown earlier that condensation of 8-H(bromo-, -nitro)mackinazolinones with aliphatic, aromatic, and
heterocyclic aldehydes occurred under various conditions [7] although only aromatic and heterocyclic aldehydes reacted.
We studied the reaction of 8-amino- (3), -acetylamino- (4), and -benzoylaminomackinazolinones (5) with aromatic
(benzaldehyde, 4-hydroxy-, -dimethylamino-, -nitro-, and 3,4-dimethoxybenzaldehydes) aldehydes 6a-e and furfurol (6f) in
order to extend the condensation of mackinazolinone with aldehydes to its other 8-substituted derivatives. For this, we first
improved the nitration method of mackinazolinone and prepared it in 92% yield (70% by the known method [11]). The reduction
of 8-nitromackinazolinone (2) with a 1:3 ratio of starting materials 2:SnCl 42H O enabled an improved method for synthesizing
2
2
of 8-aminomackinazolinone (3) to be developed. The yield was almost quantitative (98%).
O
9
10
R
1
N
3
5
N
7
1 - 5
1: R = H; 2: R = NO ; 3: R = NH
2
2
4: R = CH CONH; 5: C H CONH
3
6 5
The condensation of 8-aminomackinazolinone with aldehydes could occur at the methylene in the 4-position, as was
demonstrated using the reaction of tricyclic quinazoline alkaloids with aldehydes as an example, or at the amine in the
8-position of 3. Thus, the formation of mono- or bis-arylidene derivatives in addition to Schiff bases could be expected.
Carrying out the reaction with 4-nitrobenzaldehyde (6d) and 3 in Py at +5°C showed that the condensation proceeded slowly
and was finished after five weeks. It formed exclusively 8-[(4ꢀ-nitrobenzylidene)amino]mackinazolinone (7), which was
isolated in 53% yield (Scheme 1).
S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan,
Tashkent, fax: (99871) 120 64 75, e-mail: burkhon@rambler.ru. Translated from Khimiya Prirodnykh Soedinenii, No. 2,
March–April, 2013, pp. 259–263. Original article submitted December 27, 2012.
©
0009-3130/13/4902-0305 2013 Springer Science+Business Media New York
305

O
9
7'
O
N
10
5
N
1
CH
N
N
CHO
1'
3
H N
2
7
N
i
+
3'
5'
NO
NO
2
2
6d
3
7
i. C H N, 1:1, +5ꢁC
6
5
Scheme 1
The reaction of 3 with aromatic aldehydes containing electron-donating substituents went more difficultly under
analogous conditions. Pure products could not be isolated.
We found previously that the reaction of 1 itself with aldehydes occurred smoothly in acidic solution [7]. We carried
out the reaction of 3 with aldehydes 6a–f using a 1:2 ratio of 3:6a–f in glacial acetic acid (AcOH) in order to increase the rate
of reaction. The formation of both mono- and bis-arylidene derivatives could also be expected. However, condensation of 3
with aldehydes under reflux in glacial AcOH for 1–3 h produced 8-acetylamino-4-arylidenemackinazolinones 8a–f, i.e.,
simultaneous acetylation of the amine of 3 and condensation of the resulting 8-acetylaminomackinazolinone with aldehydes at
the methylene in the 4-position were observed. Formation of 8-acetylaminoquinazolin-4-ones was observed earlier during
reduction of 7-nitrodeoxyvasicinone using Fe in glacial AcOH [11] (Scheme 2).
O
O
H CCHN
3
8
1
4
10
N
5
N
iii
ii
CH Ar(Het)
O
8a - f
O
N
O
H N
2
H CCHN
3
i
N
N
N
4
3
iv
O
O
N
BzHN
8
BzHN
10
1
v
N
5
4
N
N
CH Ar(Het)
5
9a - f
6a-f = Ar(Het)COH
Ar(Het) = C H (a); C H -OH-4 (b); C H -N(CH ) -4 (c); C H -NO -4 (d);
6
5
6
4
6
4
3 2
6
4
2
C H -(OCH ) -3,4 (e); furyl-2 (f)
6
3
3 2
i. (CH CO) O, 20–25ꢁC; ii. AcOH, 4 : 6a-f 1:1, 117ꢁC;
3
2
iii. AcOH, 3 : 6a-f 1:2, 117ꢁC; iv. BzCl, Et N, C H , 80ꢁC;
3
6 6
v. AcOH, 5 : 6a-f 1:1, 117ꢁC
Scheme 2
8-Acetylamino-4-arylidenemackinazolinones could be formed via two pathways, i.e., preliminary acetylation of the
C-8 amine by AcOH or condensation of 3 with aromatic aldehydes to form 8-amino-4-arylidenemackinazolinones that then
underwent acylation. Therefore, we decided to acylate 8-aminomackinazolinone with acetic anhydride and benzoylchloride.
8-Acetylaminomackinazolinone (4) was prepared in almost quantitative yield (96%). Condensation of 4 with the given aldehydes
6a–f in glacial AcOH under reflux for 2–4 h gave 8-acetylamino-4-arylidenemackinazolinones 8a–f.
8-Benzoylaminomackinazolinone (5) was prepared in high (98%) yield by reacting 3 with benzoylchloride in the
presence of Et N in anhydrous benzene. Condensation of 5 with aldehydes 6a–f gave the corresponding 8-benzoylamino-
3
4-arylidenemackinazolinones 9a–f (Scheme 2).
306

Thus, the condensation occurred selectively at the methylene in the 4-position, in contrast with 3, for the reaction
with 8-acetyl(benzoyl)aminomackinazolinones. Carrying out the condensation of 3 with 6d in propionic acid gave the
bis-product 8-[(4ꢀ-nitrobenzylidene)amino]-4-(4ꢂ-nitrobenzylidene)mackinazolinone (10) (91% yield).
O
8
1
N
N
4
2''
CH
N
HC
NO
2
2'
5''
5'
10
NO
2
Condensation at both reactive centers and not acylation of the amine by propionic acid was observed if propionic acid
was used as the solvent. If the reaction of 3 was carried out inAcOH, the amine was acetylated and then reaction with aromatic
aldehydes gave 8a–f. Condensation of 3 in Py formed the Schiff base (6d as an example).
The structures of the synthesized compounds were confirmed by mass spectrometric and PMR spectroscopic data.
The PMR spectrum of 7 showed methylene protons in the 4-position with chemical shift (CS) 2.87 ppm (2H, triplet);
protons in the 2- and 3-positions, 1.78–1.88 ppm (4H, multiplet); and in the 1-position, 3.92 ppm (2H, triplet). These data led
to the conclusion that the reaction of 3 with 4-nitrobenzaldehyde occurred only at the amine.
Methylene protons in the 3-position of 8–10 had CS in the range 2.68–2.80 ppm (2H, triplet); in the 2-position, 1.82–
1.89 ppm (2H, multiplet); and in the 1-position, 3.90–3.95 ppm (2H, triplet). Methyl protons of the N(CH ) of 8c and 9c
3 2
appeared at 3.06 and 3.07 ppm (6H, singlet); the OCH of 8e and 9e, at 3.57 and 3.59 ppm (3H, singlet); aromatic protons, in
3
the range 6.30–8.49 ppm; acetyl methyl protons of 8a–f, at 2.0–2.06 ppm (3H, singlet).
The appearance of the methylene protons in the 1- and 3-positions as two triplets and the lack of a resonance for
C-4 protons at 2.85–3.0 ppm confirmed unambiguously that the condensation occurred exclusively at the C-4 atom.
EXPERIMENTAL
Mass spectra were recorded on an MS-30 instrument (Kratos); PMR spectra, in TFA + CD COOD, TFA + (CD ) SO,
3
3 2
or Py-d on a Unity 400+ instrument (operating frequency 400 MHz, HMDS internal standard, ꢃ-scale). Melting points of
5
synthesized compounds were determined on Boetius (Germany) and Mel-Temp (USA) instruments. The purity of products
and course of reactions were monitored by TLC on Sorbfil (Russia) and Whatman® UV-254 (Germany) plates using solvent
systems C H :MeOH (2:1, system A; 3:1, system B; 5:1, system C) and CHCl :MeOH (15:1, system D).
6
6
3
Mackinazolinone (1) was prepared by the literature method [5].
8-Nitromackinazolinone (2) was synthesized by the method for preparing 7-nitrodeoxyvasicinone [12].
3
Mackinazolinone (1, 4 g, 20 mmol) was dissolved in conc. H SO (8 mL, 95.72%, ꢄ = 1.835 g/cm ) with vigorous stirring and
2
4
3
cooling (ice bath) and treated dropwise at <2°C with a nitrating mixture consisting of HNO (3 mL, 59.69%, ꢄ = 1.365 g/cm )
and H SO (3 mL, ꢄ = 1.835 g/cm ). After the whole amount of the nitrating mixture was added, the mixture was stirred at
3
3
2
4
5–10°C for 1 h and just as long at room temperature and poured into ice. The resulting yellow precipitate was filtered off,
washed with H O until neutral, and dried to afford 2 (4.55 g, 92%), mp 183–184°C (MeOH) (lit. [6] mp 178–180°C).
2
8-Aminomackinazolinone (3) was prepared by the method for synthesizing 7-aminodeoxyvasicinone [13]. A three-
necked flask equipped with a mechanical stirrer and dropping funnel was charged with SnCl 42H O (55.22 g, 0.24 mol);
2
2
treated with conc. HCl (36%, 75 mL) with cooling (ice bath) and stirring; stirred for 10–15 min; treated in portions with a
suspension consisting of 2 (20 g, 0.0816 mol), EtOH (115 mL), and conc. HCl (38 mL); and stirred for another 10–15 min with
cooling. The ice bath was removed. Stirring was continued at room temperature (0.5 h). The reaction was continued with
vigorous stirring on a boiling-water bath for 2 h. The mixture was left overnight, diluted with H O, and made basic with
2
NaOH solution (10%) until strongly basic (pH 11). The resulting precipitate was filtered off, washed with distilled H O until
2
neutral, and dried. Crystallization from EtOH afforded 3 (17 g, 98%), mp 199–200°C. PMR spectrum (ꢃ, ppm, J/Hz): 8.05
(1H, d, J = 2.2, H-9), 7.70 (1H, dd, J = 8.4, 2.2, H-7), 7.50 (1H, d, J = 8.4, H-6), 3.78 (2H, t, J = 5.8, H-1), 2.82 (2H, t, J = 6.5,
H-4), 1.74–1.80 (4H, m, H-2, 3).
307

8-Acetylaminomackinazolinone (4). A one-necked flask was charged with 3 (5 g, 24.8 mmol) and treated with
acetic anhydride (35 mL). A white precipitate started to form immediately. The mixture was left overnight. The precipitate
was filtered off, washed with C H , and dried. Recrystallization from EtOH afforded 4 (5.76 g, 96%), mp 263–264°C.
6
6
PMR spectrum (ꢃ, ppm, J/Hz): 8.71 (1H, s, NH), 8.20 (1H, d, J = 2.1, H-9), 7.82 (1H, dd, J = 9.0, 2.1, H-7), 7.63 (1H, d, J = 9.0,
H-6), 3.84 (2H, t, J = 5.6, H-1), 2.87 (2H, t, J = 6.2, H-4), 2.14 (3H, s, CH CO), 1.77–1.84 (4H, m, H-2, 3).
3
8-Benzoylaminomackinazolinone (5). A mixture of 3 (3 g, 14 mmol), benzoylchloride (2.09 mL, 2.55 g,
3
3
18.2 mmol, ꢄ = 1.2187 g/cm ), and freshly distilled Et N (2.54 mL, 18.2 mmol, ꢄ = 0.7229 g/cm ) in anhydrous C H
3
6 6
(200 mL) was refluxed on a water bath for 4 h and cooled to room temperature. The resulting crystals were filtered off, washed
first with C H and then H O, and dried. Recrystallization from EtOH afforded 5 (4.3 g, 98%), mp 222–223°C (EtOH).
6
6
2
PMR spectrum (ꢃ, ppm, J/Hz): 8.98 (1H, s, NH), 8.42 (1H, d, J = 2.1, H-9), 7.93 (1H, dd, J = 9.0, 2.1, H-7), 7.48 (2H, d, J = 7.5,
H-2ꢀ, 6ꢀ), 7.37 (1H, d, J = 9.0, H-6), 7.26 (1H, t, J = 7.5, H-4ꢀ), 7.13 (2H, t, J = 7.5, H-3ꢀ, 5ꢀ), 3.86 (2H, t, J = 6.0, H-1), 2.96 (2H,
t, J = 6.6, H-4), 1.77–1.82 (2H, m, H-2), 1.70–1.74 (2H, m, H-3).
8-[(4ꢀ-Nitrobenzylidene)amino]mackinazolinone (7). Compounds 3 (0.1 g, 0.46 mmol) and 6d (76 mg, 0.50 mmol)
were dissolved in freshly distilled Py (5 mL) and left at +5°C for five weeks. The course of the reaction was monitored by
TLC. The resulting crystals were filtered off, washed several times with cyclohexane, and dried to afford 7 (85 mg, 53%),
mp 244–245°C. PMR spectrum (ꢃ, ppm, J/Hz): 8.93 (1H, s, CHAr), 8.33 (2H, d, J = 8.8, H-2ꢀ, 6ꢀ), 8.20 (2H, d, J = 8.8, H-3ꢀ,
5ꢀ), 7.96 (1H, d, J = 2.5, H-9), 7.7 (1H, dd, J = 8.5, 2.5, H-7), 7.60 (1H, d, J = 8.5, H-6) 3.92 (2H, t, J = 5.6, H-1), 2.87 (2H, t,
J = 6.6, H-4), 1.78–1.88 (4H, m, H-2, 3).
8-Acetylamino-4-benzylidenemackinazolinone (8a). Method a: Compound 4 (0.215 g, 1.0 mmol) was dissolved
3
in glacial AcOH (5 mL), treated with benzaldehyde (0.2 mL, 0.21 g, 2.0 mmol, ꢄ = 1.0498 g/cm ), refluxed for 1–3 h, and left
overnight. The solvent was distilled off. The solid was recrystallized from aqueous DMF to afford 8a (0.288 g, 72%),
mp 227–228°C, R 0.77 (system B).
f
3
Method b: Compound 3 (0.3 g, 1.16 mmol) and benzaldehyde (0.124 mL, 0.13 g, 1.22 mmol, ꢄ = 1.0498 g/cm ) were
dissolved in glacial AcOH (5 mL), refluxed for 2–4 h, and left overnight. The resulting crystals were filtered off, washed with
H O, and dried. Recrystallization from aqueous DMF afforded 8a (0.233 g, 58%). PMR spectrum (ꢃ, ppm, J/Hz): 8.89 (1H,
2
s, NH), 8.31 (1H, d, J = 2.0, H-9), 7.81 (1H, dd, J = 9.0, 2.0, H-7), 7.53 (1H, s, CHPh), 7.47 (1H, d, J = 9.0, H-6), 7.11–7.17
(5H, m, H-2ꢀ, 3ꢀ, 4ꢀ, 5ꢀ, 6ꢀ), 3.92 (1H, t, J = 6.0, H-1), 2.74 (2H, t, J = 5.8, H-3), 2.06 (3H, s, CH CO), 1.85 (2H, m, H-2).
3
8-Acetylamino-4-(4ꢀ-hydroxybenzylidene)mackinazolinone (8b). Method a: Analogously as above 4 (0.107 g,
0.5 mmol) and 4-hydroxybenzaldehyde (0.122 g, 1.0 mmol) afforded 8b (0.185 g, 87%), mp 321–322°C (aq. DMF), R 0.75
f
(system B).
Method b: Compound 3 (0.3 g, 1.16 mmol) and 4-hydroxybenzaldehyde (0.146 g, 1.2 mmol) afforded by the above
method 8b (0.261 g, 62%). PMR spectrum (ꢃ, ppm, J/Hz): 8.78 (1H, s, NH), 8.26 (1H, d, J = 2.4, H-9), 7.80 (1H, dd, J = 9.1,
2.4, H-7), 7.45 (1H, s, CHAr), 7.43 (1H, d, J = 9.1, H-6), 7.17 (2H, d, J = 8.6, H-2ꢀ, 6ꢀ), 6.68 (2H, d, J = 8.6, H-3ꢀ, 5ꢀ), 3.90 (2H,
t, J = 5.6, H-1), 2.71 (2H, t, J = 6.7, H-3), 2.01 (3H, s, CH CO), 1.85 (2H, m, H-2).
3
8-Acetylamino-4-(4ꢀ-dimethylaminobenzylidene)mackinazolinone (8c). Method a: Compound 4 (0.215 g, 1 mmol)
and 4-dimethylaminobenzaldehyde (0.298 g, 2 mmol) afforded analogously as above 8c (0.38 g, 84%), mp 248–249°C (DMF),
R 0.62 (system B).
f
Method b: Compound 3 (0.3 g, 1.16 mmol) and 4-dimethylaminobenzaldehyde (0.18 g, 1.2 mmol) analogously as
above afforded 8c (0.372 g, 64%). PMR spectrum (ꢃ, ppm, J/Hz): 8.86 (1H, s, NH), 8.34 (1H, d, J = 2.4, H-9), 7.82 (1H, dd,
J = 9.0, 2.3, H-7), 7.55 (1H, s, CHAr), 7.50 (1H, d, J = 9.0, H-6), 7.39 (2H, d, J = 9.4, H-2ꢀ, 6ꢀ), 7.36 (2H, d, J = 9.4, H-3ꢀ, 5ꢀ),
3.93 (2H, t, J = 5.9, H-1), 3.06 [6H, s, N(CH ) ], 2.68 (2H, t, J = 6.0, H-3), 2.01 (3H, s, CH CO), 1.86 (2H, m, H-2).
3 2
3
8-Acetylamino-4-(4ꢀ-nitrobenzylidene)mackinazolinone (8d). Method a: Compound 4 (0.215 g, 1 mmol) and
4-nitrobenzaldehyde (0.302 g, 2 mmol) analogously as above afforded 8d (0.418 g, 92%), mp 299–300°C (DMF), R 0.74
f
(system B).
Method b: Compound 3 (0.3 g, 1.16 mmol) and 4-nitrobenzaldehyde (0.19 g, 1.2 mmol) according to the above
method afforded 8d (0.37 g, 82%). PMR spectrum (ꢃ, ppm, J/Hz): 8.81 (1H, s, NH), 8.32 (1H, d, J = 2.4, H-9), 7.99 (2H, d,
J = 8.8, H-3ꢀ, 5ꢀ), 7.83 (1H, dd, J = 8.9, 2.4, H-7), 7.59 (1H, s, CHAr), 7.51 (1H, d, J = 8.9, H-6), 7.33 (2H, d, J = 8.8, H-2ꢀ, 6ꢀ),
3.94 (2H, t, J = 5.8, H-1), 2.70 (2H, t, J = 5.0, H-3), 2.01 (3H, s, CH CO), 1.86 (2H, m, H-2).
3
8-Acetylamino-4-(3ꢀ,4ꢀ-dimethoxybenzylidene)mackinazolinone (8e). Method a: Compound 4 (0.107 g, 0.5 mmol)
and 3,4-dimethoxybenzaldehyde (0.166 g, 1.0 mmol) according to the above method afforded 8e (0.207 g, 88%), mp 225–
226°C (EtOH), R 0.88 (system B).
f
308

Method b: Compound 3 (0.3 g, 1.16 mmol) and 3,4-dimethoxybenzaldehyde (0.2 g, 1.2 mmol) according to the
+
+
above method afforded 8e (0.307 g, 65%). Mass spectrum (m/z, %): 405 (56.6) [M] , 404 (100) [M – 1] , 390 (18.8)
+
+
+
+
[M – CH ] , 374 (2.8) [M – OCH ] , 362 (17.5) [M – CH CO] , 347 (2.1) [M – CH CONH] , 332 (1.4), 276 (6.3), 257 (7.7),
3
3
3
3
229 (5.0), 215 (7.0), 182 (12.6), 171 (1.4), 143 (1.4), 119 (4.2), 105 (13.3), 78 (7.0). PMR spectrum (ꢃ, ppm, J/Hz): 8.79 (1H,
s, NH), 8.26 (1H, d, J = 2.4, H-9), 7.80 (1H, dd, J = 8.8, 2.4, H-7), 7.46 (1H, s, CHAr), 7.45 (1H, d, J = 8.9, H-6), 6.96 (1H, dd,
J = 8.5, 2.0, H-6ꢀ), 6.81 (1H, d, J = 2.0, H-2ꢀ), 6.72 (1H, d, J = 8.5, H-5ꢀ), 3.91 (2H, t, J = 5.5, H-1), 3.59 (3H, s, 3ꢀ-OCH ), 3.57
3
(3H, s, 4ꢀ-OCH ), 2.75 (2H, t, J = 5.6, H-3), 2.01 (3H, s, CH CO), 1.86 (2H, m, H-2).
3
3
8-Acetylamino-4-(furfurylidene-2)mackinazolinone (8f). Method a: Compound 4 (0.107 g, 0.5 mmol) and furfurol
3
(0.082 mL, 0.096 g, 1.0 mmol, ꢄ = 1.1598 g/cm ) analogously as above afforded 8f (0.173 g, 89%), mp 273–274°C
(aq. DMF), R 0.66 (system B).
f
3
Method b: Compound 3 (0.3 g, 1.16 mmol) and furfurol (0.11 mL, 0.127 g, 1.3 mmol, ꢄ = 1.1598 g/cm ) afforded 8f
+
+
+
+
(0.32 g, 82%). Mass spectrum (m/z, %): 405 (56.6) [M] , 404 (100) [M – 1] , 390 (18.8) [M – CH ] , 374 (2.8) [M – OCH ] ,
3
3
+
+
362 (17.5) [M – CH CO] , 347 (2.1) [M – CH CONH] , 332 (1.4), 276 (6.3), 257 (7.7), 229 (5.0), 215 (7.0), 182 (12.6), 171
3
3
(1.4), 143 (1.4), 119 (4.2), 105 (13.3), 78 (7.0). PMR spectrum (ꢃ, ppm, J/Hz): 8.78 (1H, s, NH), 8.23 (1H, d, J = 2.3, H-9),
7.79 (1H, dd, J = 9.0, 2.3, H-7), 7.41 (1H, d, J = 9.0, H-6), 7.39 (1H, d, J = 1.7, H-5ꢀ), 7.33 (1H, s, CHHet), 6.71 (1H, d, J = 3.8,
H-3ꢀ), 6.30 (1H, dd, J = 3.8, 1.7, H-4ꢀ), 3.93 (2H, t, J = 5.5, H-1), 2.79 (2H, t, J = 6.8, H-3), 2.00 (3H, s, CH CO), 1.84 (2H, m,
3
H-2).
Mixed samples of compounds 8a–f prepared by methods a and b did not give melting-point depression.
8-Benzoylamino-4-benzylidenemackinazolinone (9a). Compound 5 (0.319 g, 1.0 mmol) dissolved in glacialAcOH
3
(5 mL) was treated with benzaldehyde (0.12 mL, 0.127 g, 1.2 mmol, ꢄ = 1.0498 g/cm ) and refluxed for 3–5 h. The solvent
was distilled off. The solid was recrystallized from MeOH to afford 9a (0.228 g, 56%), mp 226–227°C, R 0.73 (system B).
f
PMR spectrum (ꢃ, ppm, J/Hz): 9.01 (1H, s, NH), 8.43 (1H, d, J = 2.1, H-9), 7.97 (1H, dd, J = 8.9, 2.1, H-7), 7.48–7.54 (4H, m,
CHAr, H-6, 2ꢀ, 6ꢀ), 7.27 (1H, t, J = 7.4, H-4ꢀ), 7.12–7.17 (7H, m, H-3ꢀ, 5ꢀ, 2ꢂ, 3ꢂ, 4ꢂ, 5ꢂ, 6ꢂ), 3.93 (2H, t, J = 5.6, H-1), 2.75 (2H,
t, J = 6.7, H-3), 1.83–1.88 (2H, m, H-2).
8-Benzoylamino-4-(4ꢂ-hydroxybenzylidene)mackinazolinone (9b). Compound 5 (0.319 g, 1.0 mmol) and
4-hydroxybenzaldehyde (0.146 g, 1.2 mmol) afforded analogously as above 9b (0.262 g, 62%), mp 275–276°C (EtOH),
+
+
R 0.84 (system B). Mass spectrum (m/z, %): 423 (91.6) [M] , 335 (11.2), 319 (51.7), 318 (13.3) [M – C H CO] , 281 (11.9),
f
6 5
238 (3.5), 225 (4.2), 198 (3.5), 184 (4.2), 157 (7.0), 133 (14.7), 109 (23.8), 105 (100), 76 (77.6). PMR spectrum (ꢃ, ppm,
J/Hz): 9.02 (1H, s, NH), 8.41 (1H, d, J = 2.0, H-9), 7.96 (1H, dd, J = 9.0, 2.0, H-7), 7.46–7.50 (4H, m, CHAr, H-6, 2ꢀ, 6ꢀ),7.27
(1H, t, J = 7.6, H-4ꢀ), 7.18 (2H, d, J = 8.8, H-2ꢂ, 6ꢂ), 7.14 (2H, t, J = 7.6, H-3ꢀ, 5ꢀ), 6.68 (2H, d, J = 8.8, H-3ꢂ, 5ꢂ), 3.92 (2H, t,
J = 5.5, H-1), 2.72 (2H, t, J = 5.5, H-3), 1.84–1.87 (2H, m, H-2).
8-Benzoylamino-4-(4ꢂ-dimethylaminobenzylidene)mackinazolinone (9c). Compound 5 (0.319 g, 1.0 mmol) and
4-dimethylaminobenzaldehyde (0.178 g, 1.2 mmol) afforded as above 9c (0.254 g, 56%), mp 273–274°C (aq. DMF), R 0.71
f
+
+
+
+
(system B). Mass spectrum (m/z, %): 450 (100) [M] , 449 (92.3) [M – 1] , 435 (1.4) [M – 1] , 345 (8.4) [M – C H CO] , 324
6
5
(1.05), 298 (3.5), 281 (1.0), 253 (1.5), 197 (1.8), 183 (1.4), 145 (1.4), 105 (20.3), 76 (6.3). PMR spectrum (ꢃ, ppm, J/Hz): 9.05
(1H, s, NH), 8.49 (1H, d, J = 2.1, H-9), 7.98 (1H, dd, J = 9.0, 2.1, H-7), 7.50–7.57 (4H, m, CHAr, H-6, 2ꢀ, 6ꢀ), 7.40 (2H, d,
J = 9.0, H-2ꢂ, 6ꢂ), 7.37 (2H, d, J = 9.0, H-3ꢂ, 5ꢂ), 7.27 (1H, t, J = 7.4, H-4ꢀ), 7.15 (2H, t, J = 7.4, H-3ꢀ, 5ꢀ), 3.95 (2H, t, J = 5.7,
H-1), 3.07 [6H, s, N(CH ) ], 2.69 (2H, t, J = 6.4, H-3), 1.84–1.89 (2H, m, H-2).
3 2
8-Benzoylamino-4-(4ꢂ-nitrobenzylidene)mackinazolinone (9d). Compound 5 (0.319 g, 1.0 mmol) and
4-nitrobenzaldehyde (0.166 g, 1.1 mmol) afforded analogously as above 9d (0.303 g, 84%), mp 280–281°C (aq. DMF),
R 0.66 (system B). PMR spectrum (ꢃ, ppm, J/Hz): 9.04 (1H, s, NH), 8.48 (1H, d, J = 2.3, H-9), 8.0 (2H, d, J = 8.9, H-3ꢂ, 5ꢂ),
f
7.97 (1H, dd, J = 8.9, 2.3, H-7), 7.57 (1H, d, J = 8.9, H-6), 7.5 (2H, d, J = 7.6, H-2ꢀ, 6ꢀ), 7.34 (1H, d, J = 8.9, H-2ꢂ, 6ꢂ), 7.27 (1H,
t, J = 7.6, H-4ꢀ), 7.15 (2H, t, J = 7.6, H-3ꢀ, 5ꢀ), 3.95 (2H, t, J = 5.8, H-1), 2.72 (2H, t, J = 5.0, H-3), 1.87–1.90 (2H, m, H-2).
8-Benzoylamino-4-(3ꢂ,4ꢂ-dimethoxybenzylidene)mackinazolinone (9e). Compound 5 (0.319 g, 1.0 mmol) and
3,4-dimethoxybenzaldehyde (0.182 g, 1.1 mmol) afforded analogously as above 9e (0.306 g, 65%), mp 257–258°C (C H ),
6
6
R 0.79 (system B). PMR spectrum (ꢃ, ppm, J/Hz): 9.02 (1H, s, NH), 8.42 (1H, d, J = 2.2, H-9), 7.96 (1H, dd, J = 9.0, 2.2,
f
H-7), 7.48–7.50 (4H, m, CHAr, H-6, 2ꢀ, 6ꢀ), 7.27 (1H, t, J = 7.5, H-4ꢀ), 7.14 (2H, t, J = 7.5, H-3ꢀ, 5ꢀ), 6.97 (1H, dd, J = 8.7, 1.9,
H-6ꢂ), 6.81 (1H, d, J = 1.9, H-2ꢂ), 6.72 (1H, d, J = 8.7, H-5ꢂ), 3.93 (2H, t, J = 5.6, H-1), 3.57 (3H, s, 3ꢂ-OCH ), 3.59 (3H, s,
3
4ꢂ-OCH ), 2.76 (2H, t, J = 5.6, H-3), 1.85–1.89 (2H, m, H-2).
3
8-Benzoylamino-4-(furfurylidene-2)mackinazolinone (9f). Compound 5 (0.319 g, 1.0 mmol) and furfurol
3
0.1 mL (0.116 g, 1.2 mmol, ꢄ = 1.1598 g/cm ) afforded analogously as above 9f (0.342 g, 86%), mp 239–240°C (aq. DMF),
309

+
+
R 0.73 (system B). Mass spectrum (m/z, %): 397 (65.0) [M] , 368 (20.3), 356 (13.3), 343 (36.4), 292 (4.2) [M – C H CO] ,
f
6 5
264 (4.2), 238 (7.7), 212 (5.6), 196 (3.5), 155 (2.1), 117 (2.1), 105 (100), 76 (63.6). PMR spectrum (ꢃ, ppm, J/Hz): 9.02 (1H,
s, NH), 8.39 (1H, d, J = 2.3, H-9), 7.94 (1H, dd, J = 9.0, 2.3, H-7), 7.49 (2H, d, J = 7.4, H-2ꢀ, 6ꢀ), 7.47 (1H, d, J = 9.0, H-6), 7.40
(1H, d, J = 1.8, H-5ꢂ), 7.35 (1H, s, CHHet), 7.26 (1H, t, J = 7.4, H-4ꢀ), 7.14 (2H, t, J = 7.4, H-3ꢀ, 5ꢀ), 6.72 (1H, d, J = 3.7, H-3ꢂ),
6.31 (1H, dd, J = 3.7, 1.8, H-2ꢂ), 3.95 (2H, t, J = 5.5, H-1), 2.80 (2H, t, J = 5.5, H-3), 1.82–1.87 (2H, m, H-2).
8-[(4ꢀ-Nitrobenzylidene)amino]-4-(4ꢂ-nitrobenzylidene)mackinazolinone (10). Amixture of 8e (0.2 g, 0.92 mmol)
and 4-nitrobenzaldehyde (0.279 g, 1.85 mmol) in propionic acid (4 mL) was refluxed on an oil bath for 1 h and cooled. The
resulting yellow precipitate was filtered off, washed with H O, and dried. Recrystallization from DMF afforded 10 (0.409 g,
2
91%), mp 279–280°C, R 0.84 (system D). PMR spectrum (ꢃ, ppm, J/Hz): 9.69 (1H, s, CH=N), 8.26 (1H, d, J = 2.2, H-9), 8.04
f
(2H, d, J = 8.7, H-3ꢀ, 5ꢀ), 8.02 (2H, d, J = 8.7, H-2ꢀ, 6ꢀ), 7.81 (2H, d, J = 8.7, H-3ꢂ, 5ꢂ), 7.78 (1H, dd, J = 8.7, 2.2, H-7), 7.73 (1H,
d, J = 8.7, H-6), 7.68 (1H, s, CHAr), 7.36 (2H, d, J = 8.7, H-2ꢂ, 6ꢂ), 3.94 (2H, t, J = 6.5, H-1), 2.72 (2H, t, J = 6.4, H-3), 1.88
(2H, m, H-2).
ACKNOWLEDGMENT
The work was supported financially by Basic Research of TsNT, RU (Project No. FA-F7-T207).
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