Synthesis and properties of 6,7,8-substituted 2-(4-oxo-3,4-dihydro-2-quinazolinyl)-acetonitriles

Article abstract of DOI:10.1023/A:1015639404863

2-N-Oxo-3,4-dihydro-2-quinazolinyl)acetonitriles have been obtained by the interaction of α-cyanoethylthioiminoacetate with substituted anthranilic acids. Prototropy became apparent in the series of synthesized compounds. Reactions of the 2-(4-oxo-3,4-dihydro-2-quinazolinyl)acetonitriles have been carried out with (hereto)aromatic aldehydes leading to the formation of 3-aryl-2-(4-oxo-3,4-dihydro-2-quinazolinyl)acrylonitriles.

Full text of DOI:10.1023/A:1015639404863

Chemistry of Heterocyclic Compounds, Vol. 38, No. 3, 2002
SYNTHESIS AND PROPERTIES
OF 6,7,8-SUBSTITUTED 2-(4-OXO-
3,4-DIHYDRO-2-QUINAZOLINYL)-
ACETONITRILES
Yu. M. Volovenko, O. V. Khilya, T. A. Volovnenko, and T. V. Shokol
2-(4-Oxo-3,4-dihydro-2-quinazolinyl)acetonitriles have been obtained by the interaction of
α-cyanoethylthioiminoacetate with substituted anthranilic acids. Prototropy became apparent in the
series of synthesized compounds. Reactions of the 2-(4-oxo-3,4-dihydro-2-quinazolinyl)acetonitriles
have been carried out with (hetero)aromatic aldehydes leading to the formation of 3-aryl-2-(4-oxo-3,4-
dihydro-2-quinazolinyl)acrylonitriles.
Keywords: anthranilic acid, 3-aryl-2-(4-oxo-3,4-dihydro-2-quinazolinyl)acrylonitrile, 2-(4-oxo-3,4-
dihydro-2-quinazolinyl)acetonitrile, 4-oxo-3,4-dihydroquinazolinone, 3-pyridyl-2-(4-oxo-3,4-dihydro-2-
quinazolinyl)acrylonitrile, α-cyanothioacetamide, prototropy.
2-(4-Oxo-3,4-dihydro-2-quinazolinyl)acetonitrile (1a) is widely used in the synthesis of dyestuffs of
various classes, including styrenes [1], azo dyes [2-5], coumarins [6], and isoindolines [7,8].
Derivatives of 4-oxo-3,4-dihydroquinazolines display significant antimicrobial activity [9]. The
condensation products of 3-phenyl- and 3-pyridyl-2-methyl-4(3H)-quinazolinones with aromatic aldehydes may
be used for the treatment of several neurological disorders (Parkinson's disease, epilepsy, ischemia) [10]. It is
known that certain styrylquinazolinones are anticancer medicines [11]. These facts caused our interest in the
study of the properties and reactivity of derivatives of 4-oxo-3,4-dihydroquinazolines.
Nitrile 1a was obtained for the first time in 1962 by the interaction of anthranilic acid with the
extremely unstable and difficultly available ethyliminocyanoacetate [12]. Methods of synthesis for this
compound have been patented from anthranilic acid amide and cyanoacetic acid ethyl ester [13] or isatoic
anhydride and cyanoacetic acid amide [14] in an inert atmosphere. The use of substituted amides of anthranilic
and cyanoacetic acids enabled the synthesis of a large number of different 3,5,6,7,8-substituted 2-(4-oxo-3,4-
dihydro-2-quinazolinyl)acetonitriles [13-15]. Syntheses of nitrile 1a and its 3-N-derivatives have also been
described by the recyclization of 2-cyanomethyl-3,1-benzoxazin-4(H)-one with formamide [9,16], ammonium
acetate, and substituted anilines [17-19]. It is impossible to consider these methods as being preparative due to
the required multistage synthesis of the initial 2-cyanomethylbenzoxazinone. Also the preparation of nitrile 1a
by the sequential bromination and cyanation of 2-methyl-4(3H)-quinazolinones is laborious [20]. In our opinion
the most acceptable method of synthesis was described by the authors of [21], who obtained compound 1a in
good yield by the interaction of anthranilic acid with α-cyanothioacetamide (2) with its methylthio derivative.
__________________________________________________________________________________________
Kiev Taras Shevchenko National University, Kiev 01033, Ukraine; e-mail: olgakh@mail.univ.kiev.ua.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 350-359, March, 2002. Original article
submitted November 20, 2000; revision submitted July 17, 2001.
314
0009-3122/02/3803-0314$27.00©2002 Plenum Publishing Corporation

Since in [21] the synthesis of only nitrile 1a itself was described we decided to determine the scope of
applicability of this method, introducing into the reaction anthranilic acids with substituents of various
electronic nature.
The substituted anthranilic acids were introduced into an alcoholic (methanolic, ethanolic) solution of
α-cyanoiminothioacetic acid ethyl ester (3) and refluxed, checking the reaction chromatographically. Solution of
the anthranilic acid was observed and after a certain time a precipitate of the corresponding nitrile 1 occurred, as
a rule in chromatographically pure form. The reaction proceeds readily both in ethanol [21] and in methanol in
which the starting materials are better soluble. Anthranilic acids introduced into the reaction contained electron-
donating [5-Me, 5-Et, 5-iso-Pr, 3,5-(Me)2, 4,5-(MeO)2, N-Me] and electron-withdrawing (5-F, -Cl, -Br, -I, -CF3,
NO2, 3,5-Cl2, 3-Cl) substituents, and also anthranilic acid itself.
R1
CO2H
NH2
O
R1
R2
2
R
NH
SEt
S
R3
EtBr
EtONa
NC
NC
CN
N
NH
NH2
R3
2
3
1a–k
1 a, k R1 = H, b, e R1 = Me, c R1 = Et, d R1 = i-Pr, f R1 = OMe, g R1 = Br, h R1 = Cl, i R1 = I,
j R1 = F; a–e, g–j R2 = H, f R2 = OMe, k R2 = Cl; a–d, f–k R3 = H, e R3 = Me
Compounds obtained previously were 1a [21], 1g [17], 1b,h and 2-(6-nitro-4-oxo-3,4-dihydro-2-
quinazolinyl)acetonitrile [13].
It should be mentioned that in numerous attempts to synthesize products 1 by the procedure of [21,
method C] in which equimolar amounts of α-cyanothioacetamide 2 and anthranilic acid, and a 10% excess of
sodium ethylate and alkyl halide were used, yields did not exceed 57-70%. We found that the introduction of a
small excess of 2 (10%) and alkyl halide (20%) significantly increased the yield of product, which in many
cases required no further purification.
Compounds 1 were practically colorless high-melting crystalline substances.
The form of the substituent in position 5 of the anthranilic acid molecule proved to have a definite effect
on the yields of compound 1.
The presence of bulky substituents close to the reaction center (amino group) reduces the yield of
reaction product, which is probably linked with steric hindrance. For example, on interacting
α-cyanothioacetamide 2 with N-methylanthranilic acid the yield of 2-(1-methyl-4-oxo-1,4-dihydro-2-
1
quinazolinyl)acetonitrile did not exceed 20% (according to H NMR spectra), in spite of extended refluxing
(30 h), or more rigid reaction conditions such as fusing at 130-150°C.
The presence of halogen at position 5 of anthranilic acid did not reduce the yield of products 1
compared with yields when an alkyl substituent was present at this position. However with 3-chloro- and 3,5-
dichloroanthranilic acids the reaction generally did not proceed. This is evidently caused by the combination of
two negative factors, steric hindrance and a reduction in the basicity of the amino group under the influence of
the neighboring halogen.
The appearance of a strong electron-withdrawing group (CF3, NO2) at position 5 of the anthranilic acid
molecule proved to have a marked deactivating effect on the course of the reaction.
The reaction of α-cyanothioacetamide 2 with 5-nitroanthranilic acid did not occur either on extended
refluxing (30 h) or on fusing the reactants, but with 5-trifluoromethylanthranilic acid the product was formed in
low yield. The products of the interaction of compound 2 with 5-trifluoromethylanthranilic and N-methyl-
anthranilic acids were not isolated in a pure state.
The characteristics of compounds 1a-k are given in Table 1.
315

TABLE 1. Characteristics of 2-(4-Oxo-3,4-dihydro-2-quinazolinyl)-
acetonitriles 1a-k
Found, %
——————
Com-
pound
Empirical
formula
mp, °С (BuOH)
Rf *
Yield, %
Calculated, %
N
Hal
C10H7N3O
C11H9N3O
235
94*2, 70
87*2, 61
1a
1b
21.39
21.09
—
250-252
0.36
(224-226 [13])
C12H11N3O
C13H13N3O
C12H11N3O
C12H11N3O3
C10H6BrN3O
C10H6ClN3O
19.82
—
—
—
—
238-240
0.36
0.35
0.35
0.36
0.33
0.34
65
1c
1d
1e
1f
19.71
18.54
18.49
252
74*2
19.38
260-261
287-288
266-268
57
19.71
17.17
17.14
59
16.16
30.13
30.26
59
1g
1h
15.91
19.39
19.13
16.31
254-256*3,
60
16.14
(243-245 [13])
C10H6IN3O
C10H6FN3O
C10H6ClN3O
13.69
236-238
245-247
265-267
0.36
0.33
0.34
60
67
48
1i
13.51
20.63
20.68
—
1j
1k
18.82
16.21
16.14
19.13
_______
* Solvent system: CHCl3–MeOH, 9:1.
*2 Yield from the procedure described in Experimental.
*3 Solvent DMF.
The following were observed in the 1H NMR spectra of compounds 1a-k: a characteristic signal for the
methylene group at 4.13-4.19 ppm, signals for the appropriately substituted aromatic part of the molecule, and a
signal for the N–H proton of the quinazolone ring at 12.3-12.6 ppm (Table 2).
It is noteworthy that in all the spectra the multiplets of the aromatic protons were duplicated with low
intensity signals (10-15% of the main signal) shifted towards high field by 0.1-0.2 ppm relative to the
corresponding main signals. Another characteristic was the presence of two broadened different-intensity
singlets at 10.7 and 11.3 ppm which disappeared on adding D2O. We propose the presence of a impurity in the
synthesized products 1. However all our numerous attempts to purify them were unsuccessful. We consider that
the data obtained may indicate the presence of prototropy in these substances with the equilibrium displaced to
the side of product 1.
O
R1
NH
1
CN
R2
N
H
R3
4
It should be mentioned that on increasing the temperature a further displacement in the equilibrium is
1
observed in the direction of isomer 1, which was recorded by H NMR spectroscopy (see Fig. 1 for compound
1g).
316

TABLE 2. 1H NMR Spectra of Compounds 1b-k
1H NMR, δ, ppm, J (Hz)*
Com-
–CH2–, (2H, s)
NH
pound
5-H
6-H
7-H
8-H
Alk
(1H, br. s)
4.15
4.15
4.16
4.15
4.13
4.15
4.16
4.17
7.91 (1H, br. s)
—
—
—
—
—
—
—
—
7.67 (1H, dd,
7.56 (1H, d, 3J = 8)
7.59 (1Н, d, 3J = 8.5)
7.61 (1Н, d, 3J = 8.5)
—
2.45 (3Н, s, 6-Me)
12.38
12.32
12.37
12.33
12.29
12.65
12.64
12.59
1b
1c
1d
1e
1f
3J = 8, 4J = 2)
7.91 (1H, d, 4J = 2)
7.93 (1H, d, 4J = 2)
7.73 (1H, d, 4J = 2)
7.42 (1H, s)
7.69 (1H, dd,
2.74 (2Н, q, 3J = 7, 6-Et),
3J = 8.5, 4J = 2)
1.23 (3Н, t, 3J = 7, 6-Et)
7.75 (1H, dd,
3.06 (1Н, septet, i-Pr-6),
1.26 (6Н, d, 3J = 7, i-Pr-6)
3J = 8.5, 4J = 2)
7.52 (1H, d, 4J = 2)
2.52 (3Н, s, 8-Me),
2.40 (3Н, s, 6-Me)
—
7.14 (1H, s)
3.92 (3Н, s, 6-OMe),
3.87 (3Н, s, 7-OMe)
8.16 (1H, d, 4J = 2)
8.02 (1H, d, 4J = 2)
8.35 (1H, d, 4J = 2)
7.95 (1Н, dd,
7.62 (1H, d, 3J = 8.5)
7.69 (1H, d, 3J = 8.5)
7.46 (1H, d, 3J = 8.5)
—
—
—
1g
1h
1i
3J = 8.5, 4J = 2)
7.85 (1Н, dd,
3J = 8.5, 4J = 2)
8.1 (1Н, dd,
J = 8.5, 4J = 2)
4.18
4.19
7.69-7.79 (3H, m)
—
7.69-7.79 (3H, m)
—
7.69-7.79 (3H, m)
—
—
12.60
12.51
1j
1k
8.09 (1H, d, 3J = 8.5)
7.57 (1Н, dd,
7.75 (1H, d, 4J = 2)
3J = 8.5, 4J = 2)
_______
* Signals of quinazolone ring protons.

Content, %
T, K
Fig. 1. Dependence of the content of isomer 4g on temperature.
The introduction of electron-withdrawing substituents (halogen atoms) into the benzene ring of
quinazolones 1 increases the isomer 4 content. This effect is explained logically by an increase in the mobility
of the methylene group protons.
The signal of the methine group proton of tautomer 4 overlapes with the signals of the protons of the
benzene nucleus.
It was also possible to demonstrate the presence of isomer 4 with the aid of TLC by applying a large
quantity of substance to the chromatographic plate. The Rf values for tautomers 4 were 0.2 greater than the Rf
values of the corresponding tautomers 1.
The condensation of 2-cyanomethyl-4(3H)-quinazolones with aromatic aldehydes has been carried out
previously [1, 16, 21]. We have studied the condensation of compounds 1b,c,f,g,j,k with different aromatic and
some heteroaromatic aldehydes, leading to the formation of the corresponding 3-aryl- (5a-k) and 3-pyridyl-2-(4-
oxo-3,4-dihydro-2-quinazolinyl)acrylonitriles (6a,b).
O
O
CHO
R1
R2
R1
R2
NH
NH
N
Ar–CHO
CN
Ar
CN
3
N
N
R3
R3
N
6a,b
5a–k
5 a, g R1 = Me, b, i R1 = Et, c R1 = Br, d, j R1 = F, e, h, k R1 = H, f R1 = OMe;
a-d, g, i, j R2 = H, e, k R2 = Cl, f R2 = OMe, a-k R3 = H; f Ar = 4-Me2NC6H5, h Ar = 4-MeC6H4,
k Ar = 4-MeOC6H4; 6 a R1 = Me, b R1 = Br, a, b R2 = R3 = H, a Het = 4-C5H4N, b Het = 3-C5H4N
The reaction proceeds readily on refluxing a mixture of the reactants in butanol in the presence of
triethylamine. All the compounds obtained are brightly colored (yellow, orange). The physicochemical and
spectral characteristics of these compounds are given in Tables 3 and 4.
318

TABLE 3. Characteristics of 3-Aryl- and 3-Pyridyl-2-(4-oxo-3,4-dihydro-2-quinazolinyl)acrylonitriles 5a-k and 6a,b
Found, %
——————
Com-
Empirical
formula
mp, °С
Ar (Het)
Calculated, %
Rf*
UV spectrum (BuOH), λmax, nm (log ε)
Yield, %
pound
(DMF)
N
Hal
—
4-NMe2C6H4
4-NMe2C6H4
4-NMe2C6H4
4-NMe2C6H4
4-NMe2C6H4
4-NMe2C6H4
4-MeC6H4
C20H18N4O
16.63
16.96
16.54
328
313-313.5
324-324.5
329-330
334
0.74
0.72
0.72
0.65
0.68
0.63
0.75
0.74
0.66
0.74
0.74
0.38
0.37
425 (4.43), 220 (4.53)
91
87
85
89
86
80
83
83
81
83
79
70
80
5a
5b
5c
5d
5e
5f
C21H20N4O
—
425 (4.42), 220 (4.47)
16.27
C19H15BrN4O
C19H15FN4O
C19H15ClN4O
C21H20N4O3
C19H15N3O
13.86
14.18
20.40
20.22
460 (4.43), 300 (4.19), 223 (4.56)
450 (4.59), 214 (4.52)
16.94
—
16.76
16.21
15.97
9.92
460 (4.38), 300 (4.03), 235 (4.52), 208 (4.35)
420 (4.25), 328 (3.92), 208 (4.18)
315 (4.43), 230 (4.61), 208 (4.60)
315 (4.34), 236 (4.62), 206 (4.48)
333 (4.38), 235 (4.51), 215 (4.49)
335 (4.40), 215 (4.52)
10.10
14.85
—
—
>350
14.89
14.21
13.94
329-330
319
5g
5h
5i
4-MeC6H4
C18H12ClN3O
C20H17N3O2
C18H12FN3O2
C18H12ClN3O2
C17H12N4O
13.33
11.36
11.02
13.06
4-OMeC6H4
4-OMeC6H4
4-OMeC6H4
(4-pyridyl)
12.71
12.68
—
282-283
319-320
295-296
290-291
294
13.06
—
5j
13.08
12.36
12.44
10.68
10.50
330 (4.33), 240 (4.60), 208 (4.36)
370 (4.14), 330 (4.13), 275 (4.34), 223 (4.50)
277 (4.29), 225 (4.56)
5k
6a
6b
19.88
—
19.43
(3-pyridyl)
C16H9BrN4O
16.09
15.86
22.88
22.63
_______
* Solvent system: CHCl3–MeOH, 9:1.

TABLE 4. 1H NMR Spectra of Compounds 5a-k and 6a,b
1H NMR (DMSO-d6), δ, ppm, J (Hz)*
Com-
NH
–CH=
pound
5-H
2
6-H
3
7-H
4
8-H
5
Alk
6
Ar protons
9
(1H, br. s)
(1H, s)
1
7
8
7.92 (1H, br. s)
7.94 (1H, br. s)
8.17 (1H, br. s)
7.67-7.8 (3H, m)
—
—
—
—
7.64 (1H, br. d,
7.57 (1H, d,
2.45 (3Н, s, 6-Me)
12.17
8.24
7.93 (2H, d, 3J = 8.5, 2-H, 6-H);
6.86 (2H, d, 3J = 8.5, 3-H, 5-H);
3.10 (6H, s, 4-NMe2)
5a
3J = 8)
3J = 8)
7.69 (1H, br. d,
7.59 (1H, d,
2.75 (2H, q, 3J = 7, 6-Et);
1.25 (3H, t, 3J = 7, 6-Et)
12.29
12.42
12.45
12.45
12.17
12.50
8.26
8.26
8.27
8.29
8.22
8.42
7.93 (2H, d, 3J = 8.5, 2-H, 6-H);
6.86 (2H, d, 3J = 8.5, 3-H, 5-H);
3.10 (6H, s, 4-NMe2)
5b
5c
5d
5e
5f
3J = 8.5)
3J = 8.5)
7.92 (1H, br.
7.60 (1H, d,
—
—
—
7.92 (2H, d, 3J = 8, 2-H, 6-H);
6.85 (2H, d, 3J = 8, 3-H, 5-H);
3.08 (6H, s, 4-NMe2)
d, 3J = 8)
3J = 8)
7.67-7.8 (3H, m) 7.67-7.8 (3H, m)
7.93 (2H, d, 3J = 9, 2-H, 6-H);
6.87 (2H, d, 3J = 9, 3-H, 5-H);
3.09 (6H, s, 4-NMe2)
8.10 (1H, d,
7.51 (1H, dd,
—
—
7.69 (1H, d,
7.94 (2H, d, 3J = 9, 2-H, 6-H);
6.88 (2H, d, 3J = 9, 3-H, 5-H);
3.09 (6H, s, 4-NMe2)
3J = 8)
3J = 8, 4J = 2)
4J = 2)
7.45 (1H, s)
—
—
7.11 (1H, s)
3.93 (3H, s, 7-OMe);
3.89 (3H, s, 6-OMe)
7.89 (2Н, d, 3J = 8.5, 2-H, 6-H);
6.83 (2H, d, 3J = 8.5, 3-H, 5-H);
3.07 (6H, s, 4-NMe2)
7.95 (1H, br. s)
7.68 (1H, dd,
7.64 (1H, d,
7.91 (2Н, d, 3J = 8.1, 2-H, 6-H);
7.43 (2H, d, 3J = 8.1, 3-H, 5-H);
2.42 (3H, s, 4-Me)
2.47 (3H, s, 6-Me)
5g
3J = 8.5, 4J = 2)
3J = 8.5)

TABLE 4 (continued)
1
2
3
4
5
6
7
8
9
8.11 (1H, d,
—
7.74 (1H, d,
—
12.69
8.44
7.90 (2H, d, 3J = 8.1, 2-H, 6-H);
7.41 (2Н, d, 3J = 8.1, 3-H, 5-H);
2.4 (3H, s, 4-Me)
5h
3J = 8.5)
4J = 2)
7.97 (1H, d,
—
—
7.72 (1Н, dd,
3J = 8, 4J = 2)
7.64 (1Н, d,
3J = 8)
2.77 (2Н, q, 3J = 7, 6-Et);
1.26 (3H, t, 3J = 7, 6-Et)
12.47
12.63
12.59
8.41
8.39
8.42
8.02 (2Н, d, 3J = 8.7, 2-H, 6-H);
7.19 (2H, d, 3J = 8.7, 3-H, 5-H);
3.88 (3H, s, 4-OMe)
5i
4J = 2)
7.69-7.82 (3H, m)
7.69-7.82 (3H, m) 7.69-7.82 (m)
—
7.99 (2Н, d, 3J = 8.7, 2-H, 6-H);
7.16 (2H, d, 3J = 8.7, 3-H, 5-H);
3.87 (3H, s, 4-OMe)
5j
8.13 (1H, d,
7.56 (1H, dd,
—
7.74 (1H, d,
—
8.02 (2H, d, 3J = 9, 2-H, 6-H);
7.17 (2H, d, 3J = 9, 3-H, 5-H);
3.89 (3H, s, 4-OMe)
5k
3J = 8)
3J = 8, 4J = 2)
4J = 2)
8.83 (2H, d, 3J = 5.8, 2-H, 6-H);
7.96 (1H, br. s)
8.23 (1H, br. s)
—
—
7.71 (1H, dd,
7.66 (1H, d,
2.47 (3H, s, 6-Me)
—
12.65
12.83
8.47
8.54
6a
6b
7.80 (2H, d, 3J = 5.8, 3-H, 5-H)
3J = 8, 4J = 2)
3J = 8)
8.01 (1H, br. d,
7.70 (1H, d,
8.99 (1H, br. s, 2-H);
3J = 8.5)
3J = 8.5)
8.76 (1H, br. d, 3J = 5, 6-H);
8.44 (1H, br. d, 3J = 8, 4-H);
7.65 (1H, dd, 3J5-H,4-H = 8,
3J5-H,6-H = 5, 5-H)
_______
*5-H, 8-H, Alk, and NH for protons of the quinazolone ring.

We have determined the scope of the method of synthesizing 2-(4-oxo-3,4-dihydro-2-
quinazolinyl)acetonitriles [21] and have optimized the reaction conditions, which has led to an increase in the
yield of the target compounds. The existence of isomerism (prototropy) in compounds 1 is proposed.
Condensation products at the active methylene group with (hetero)aromatic aldehydes have been obtained in
good yield with compounds 1b,c,h,m,n.
EXPERIMENTAL
A check on the progress of reactions and the purity of the products synthesized was carried out by TLC
1
on Silufol UV 254 plates in chloroform–methanol, 9:1. The H NMR spectra were measured on a Varian
Mercury (300 MHz) spectrometer with TMS as internal standard. The UV spectra were taken on a Specord
UV-vis spectrometer in BuOH at concentrations ~3·10-5 M with a cell thickness of 1 cm (0.5 cm for compound
5h). Melting points were measured (at "equilibrium" according to Kofler) on a Boetius micro-hot stage with a
VEB Analytik PHMK 05 observation device. The anthranilic acids were obtained by the procedure described in
[22].
2-(4-Oxo-3,4-dihydro-2-quinazolinyl)acetonitriles (1a-c,e-k) were obtained according to [21,
method C].
General Procedure for Synthesizing 2-(4-Oxo-3,4-dihydro-2-quinazolinyl)acetonitriles 1a,b,d.
α-Cyanothioacetamide 2 (11 g, 0.11 mol) was added to a solution of sodium (2.53 g, 0.11 mol) in methanol (or
ethanol) (50 ml), the mixture was stirred, while being heated until complete solution of compound 2. Ethyl
bromide (9.6 ml, 0.12 mol) was then added, the mixture was stirred, and left for 3-4 h. The appropriate
anthranilic acid (0.1 mol) was added to the solution of compound 3 obtained, the mixture was refluxed (3-4 h),
checking the completeness of conversion chromatographically. Product 1 precipitated from the hot solution. The
mixture was cooled, the solid filtered off, washed with alcohol, and with water, dried, and recrystallized from a
suitable solvent (Tables 1 and 2).
General Procedure for Synthesizing 3-Aryl- (5a-k) and 3-Pyridyl-2-(4-oxo-3,4-dihydro-2-
quinazolinyl)acrylonitriles (6a,b). Nitrile 1 (3 mmol) was dissolved with heating in BuOH (10 ml). The
appropriate aldehyde (3 mmol) and triethylamine (3 mmol) were added. The reaction mixture was refluxed for
3-4 h, checking the course of the reaction chromatographically. The reaction mixture was cooled, the precipitate
of (5, 6) was filtered off, washed with alcohol, dried, and compounds 5 and 6 were obtained (Tables 3 and 4).
The authors are grateful to A. V. Turov (Kiev Taras Shevchenko National University) for plotting the
1H NMR spectra.
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