Condensed isoquinolines 26. Oxidation reactions of 6,11-dihydro-13H- isoquino-[3,2-b]quinazolin-13-one derivatives

Article abstract of DOI:10.1007/s10593-007-0240-5

Oxidation of the hydrobromide of 6,11-dihydro-13H-isoquino[3,2-b] quinazolin-13-one with dimethyl sulfoxide leads to 11-hydroxy-11H-isoquino[3,2- b]quinazoline-6,13-dione, and with hydrogen peroxide to the hydrobromide of 2-[(4-oxo-3,4-dihydro-2-quinazolinyl)carbonyl]benzoic acid. Salts of 5-and 6-alkyl-substituted isoquino[3,2-b]quinazolines are readily oxidized on boiling in nitrobenzene, which leads to aromatization of the isoquino[3,2-b]quinazoline system to 5-methyl-13-oxo-5H,13H-isoquino[ 3,2-b]quinazolinium perchlorate and 6-benzyl-13H-isoquino[3,2-b]quinazolin-13-one. The structures of the dehydrogenation products were established from ¹H NMR and UV spectra. The interaction of the obtained compounds with NaBH₄ has been studied.

Full text of DOI:10.1007/s10593-007-0240-5

Chemistry of Heterocyclic Compounds, Vol. 43, No. 12, 2007
CONDENSED ISOQUINOLINES
26*. OXIDATION REACTIONS
OF 6,11-DIHYDRO-13H-ISOQUINO-
[3,2- b]QUINAZOLIN-13-ONE
DERIVATIVES
L. M. Potikha, V. A. Kovtunenko, and A. V. Tarasevich
Oxidation of the hydrobromide of 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one with dimethyl
sulfoxide leads to 11-hydroxy-11H-isoquino[3,2-b]quinazoline-6,13-dione, and with hydrogen peroxide
to the hydrobromide of 2-[(4-oxo-3,4-dihydro-2-quinazolinyl)carbonyl]benzoic acid. Salts of 5- and
6-alkyl-substituted isoquino[3,2-b]quinazolines are readily oxidized on boiling in nitrobenzene, which
leads to aromatization of the isoquino[3,2-b]quinazoline system to 5-methyl-13-oxo-5H,13H-
isoquino[3,2-b]quinazolinium perchlorate and 6-benzyl-13H-isoquino[3,2-b]quinazolin-13-one. The
1
structures of the dehydrogenation products were established from H NMR and UV spectra. The
interaction of the obtained compounds with NaBH4 has been studied.
Keywords: 6-benzyl-13H-isoquino[3,2-b]quinazolin-13-one, isoquino[3,2-b]quinazoline, 2-[(4-oxo-
3,4-dihydro-2-quinazolinyl)carbonyl]benzoic acid, 6-methyl-13-oxo-5H,13H-isoquino[3,2-b]quinazoli-
nium perchlorate, oxidation.
One of the characteristic properties of secondary enamines, and imines close to them in behavior, with
an activated methylene group is the ease of carrying out oxidation reactions [2, 3]. In the case of condensed
heterocyclic systems this is aided by definite structural factors such as the presence of benzylic positions and the
possibility of forming conjugated systems in the reaction products, which also determines the main directions of
the conversions. Previously [4-8] we showed that such reactions in the condensed isoquinoline series take place
fairly readily even in the presence of relatively weak oxidizing agents like the oxygen of the air, aromatic
aldehydes, or sulfo derivatives. But their main directions are aromatization of heterosystems, as in the case of
derivatives of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one 1a,b [4, 5], or the formation of products of
dimeric structure, on oxidation of benzimidazo[1,2-b]isoquinolin-11(5H)-one [6] or 6,11-dihydro-13H-
isoquino[3,2-b]quinazolin-13-one (2) [5, 7, 8]. Oxidation is the main side reaction on interacting isoquino-
[3,2-b]quinazolin-13-one 2 with electrophilic reagents, but in certain cases this is the main direction of the
conversions, consequently it seemed to us useful to study this problem in a more detailed manner.
_______
*For Communication 25 see [1].
__________________________________________________________________________________________
Kiev Taras Shevchenko National University, Kiev 01033, Ukraine; e-mail: potikha_l@mail.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1833-1840, December, 2007. Original
article submitted January 22, 2007.
0009-3122/07/4312-1551©2007 Springer Science+Business Media, Inc.
1551

It was shown previously [5], that the proton salts of isoquino[3,2-b]quinazolin-13-one 2 are oxidized at
positions 6 and 11 by air oxygen at temperatures >180°C (heating in benzonitrile, N-methylpyrrolid-2-one),
which leads to a mixture of products of dimeric structure and 11H-isoquino[3,2-b]quinazoline-6,13-dione (3).
_
_
ClO4
ClO4
+
N
+
N
N
R
O
N
R
O
8a,b
1a,b
O
O
O2
N
N
N
N
2
O
3
H2O2
DMSO
O
H
N
OH
O
. HBr
N
N
O
HO2C
N
5
O
4
1,8 a R = H, b R = Me
It turned out that the oxidation of salt of isoquino[3,2-b]quinazoline (2·HBr) also takes place readily and
in good yield on heating in DMSO. Reaction takes place at both methylene groups and leads to the formation of
11-hydroxy-11H-isoquino[3,2-b]quinazoline-6,13-dione (4). The presence of a hydroxyl group in the structure
of the reaction product was established by spectral data, a broad band for the stretching vibrations νOH
(3200 cm-1) and νCO (1300 cm-1) in the IR spectrum, and also a broadened one-proton signal (exchanging with
D2O) at 7.37 ppm in the 1H NMR spectrum. The 1H NMR spectrum of compound 4 did not contain signals in the
region below 7.0 ppm, but the resonance of the H-11 proton is observed at 7.15 ppm (s). Assignment of the
signals was made by studying proton-proton correlations (NOE, COSY). Confirmation for the structure of 4 was
also found in the 13C NMR spectrum: 178.25 (C-6), 160.53 (C-13), 73.26 ppm (d, JCH = 162 Hz, C-11).
Additional evidence in favor of the structure of compound 4 might also be the overall similarity of the electronic
spectra of 11H-isoquino[3,2-b]quinazoline-6,13-dione (3) [9] and of 4 (see EXPERIMENTAL).
Still deeper oxidation of salt 2·HBr takes place with hydrogen peroxide. The reaction is accompanied by
fission of the isoquinoline ring and leads to 2-[(4-oxo-3,4-dihydro-2-quinazolinyl)carbonyl]benzoic acid
hydrobromide (5) . It must be said that reaction with H2O2 takes place only on heating. Extended (~10 h) storage
of a solution of 2·HBr and H2O2 in acetonitrile at room temperature did not lead to an apparent change in the
1
reaction mixture. The H NMR spectrum of compound 5 also contains no signals in the region below 7.0 ppm,
but at low field a broadening was observed in the signals for OH (13.15) and N(3′)H (12.54 ppm). On attempting
to carry out the oxidation of free base 2 with DMSO and H2O2 a more complex mixture of products was
obtained, in which the content of compounds 4 and 5 (according to data of TLC and 1H NMR spectra) was small.
1552

The preparation of aromatic derivatives of isoquino[3,2-b]quinazolin-13-one 2 is extremely interesting
both from a theoretical and a practical point of view. It should be noted that an aromatic compound with an
isoquino[3,2-b]quinazoline nucleus is mentioned previously only in one example viz. 11H-isoquino-
[3,2-b]quinazolin-11-one [10], which was obtained on high temperature oxidation of the corresponding
5,13-dihydro derivative with iodine. However the structure of this compound was not demonstrated conclusively
by the author. We expected that in the case of compound 2 and its proton salts aromatization might be carried
out by interaction with various dehydrogenating agents. However under all the conditions tried by us,
particularly heating compound 2 and its salts (2·HBr, 2·HClO4) with sulfur or iodine in high-boiling solvents and
boiling in nitrobenzene, resinification occurs or a complex mixture of products is formed, containing chiefly
products of oxidative dimerization.
_
ClO4
_
ClO4
O
O
+
N
+
N
N
N
Me
7
Me
NaBH4
B:
6
O
N
N
Me
O
N
13
N
N
. HX
. HX
N
O
12a-c
9a-c
Ar
Ar
O
O
N
N
N
N
Ar
10a-c
Ar
11
9,10,12 a Ar = Ph, X = Cl; b Ar = 3-O2NC6H4, X = Br; c Ar = 2-MeC6H4, X = Br
The desired result was obtained on heating salts of 5- and 6-alkyl-substituted isoquino[3,2-b]quinazolin-
13-ones in nitrobenzene. Such a change in the direction of oxidation in comparison with isoquinoquinazoline 2 is
evidently explained by steric hindrance to the dimerization reaction from the side of the 5- and especially the
6-alkyl substituents. So the brief (~10 min) heating of 5-methyl-13-oxo-6,13-dihydro-11H-isoquino-
[3,2-b]quinazolinium perchlorate (6) in nitrobenzene leads to 5-methyl-13-oxo-5H,13H-isoquino[3,2-b]quinazo-
1
linium perchlorate (7) (Table 1). In the H NMR spectrum of dehydrogenation product 7 the signals for the
aliphatic protons of the methylene groups were absent (see Table 2), but the low field disposition in the spectrum
of
a
series of signals indicates the presence in the heterocyclic fragment of
a
delocalized
1553

TABLE 1. Physicochemical Characteristics of Compounds 7, 10a-c
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
mp,°C*
Yield, %
C
H
Hal
N
7
C17H13ClN2O5
C23H16N2O
56.53
56.60
3.58
3.63
9.84
9.83
7.80
7.77
275-276
218-220
65
73
10a
82.05
82.12
4.70
4.79
—
8.35
8.33
10b
C23H15N3O3
72.30
72.43
3.88
3.96
—
11.01
11.02
240-242
201-203
62
59
10c ⋅HBr C24H19BrN2O
66.70
66.83
4.36
4.44
18.55
18.53
6.52
6.49
_______
*Solvent: AcOH (compounds 7, 10c·HBr) and DMF (compounds 10a,b).
TABLE 2. Spectral Characteristics of Compounds 7, 10a-c
1Н NMR spectrum, δ, ppm (J, Hz)
UV spectrum,
IR spectrum,
Com-
pound
λ
max, nm
other
signals
ν, cm-1
(ε×103)
H-11, s
10.60
Ar−H
7
3100, 1740
(br., C=O),
1595, 1470,
1305, 1074
208* (59.3),
235 (72.2),
327 (63.8),
390* (7.7)
8.89 (1Н, s, Н-6);
4.23 (3Н,
s, СН3)
8.62 (1Н, d, J = 8.0, Н-10);
8.55 (1Н, d, оJ = 8.0, Н-1);
8.26 (1Н, d, оJ = 8.0, Н-7);
8.18 (1Н, t, оJ = 8.0, Н-3);
8.10 (2Н, m, Н-4,8);
–
(ClO4 ), 755
7.78 (1Н, t, оJ = 8.0, Н-2);
7.67 (1Н, t, оJ = 8.0, Н-9)
10a
1670 (C=O,
C=N), 1495,
1440, 770,
740, 693
9.81
8.38 (1Н, d, оJ = 8.0, Н-10);
8.01 (1Н, d, оJ = 8.2, Н-1);
7.92 (1Н, d, оJ = 8.2, Н-7);
7.86 (1Н, t, оJ = 8.0, Н-3);
7.79 (1Н, d, оJ = 8.0, Н-4);
7.43 (2Н, m, Н-2,8);
4.96 (2Н,
s, СН2)
—
7.32 (2Н, d, оJ = 8.0, H-2',6');
7.24 (1Н, t, оJ = 7.8, Н-9);
7.17 (2Н, t, оJ = 8.0, H-3',5');
7.09 (1Н, t, оJ = 8.0, H-4')
10b
1670 (C=O,
C=N), 1495, 266 (83.4),
237 (89.4),
9.84
4.38 (1Н, d, оJ = 8.0, Н-10);
4.32 (1Н, s, H-2');
5.07 (2Н,
s, СН2)
1445, 1337
(NO2)
310* (53.0),
368 (12.5),
390 (23.8),
407 (38.1),
450* (6.0),
503 (11.3),
520 (9.5),
8.07 (2Н, m, Н-1,4');
8.00 (1Н, d, оJ = 8.0, Н-7);
7.90 (1Н, t, оJ = 8.0, Н-3);
7.82 (2Н, m, Н-4,6');
7.46 (3Н, m, Н-2,8,5');
7.28 (1Н, t, оJ = 8.0, Н-9)
575* (7.1)
10c·HBr 3410 (NH),
238 (160.0),
267 (110.5),
1625 (C=N), 284* (91.7),
10.44
8.62 (1Н, d, оJ = 8.0, Н-1);
8.46 (1Н, d, оJ = 8.0, Н-10);
8.15 (2Н, m, Н-3,7);
4.91 (2Н,
s, СН2);
2.61 (3Н,
s, СН3)
1725 C=O),
750
311* (62.0),
370 (23.3),
390 (37.7),
410 (59.1),
445* (13.5),
500 18.0),
517 (17.0),
580* (10.8)
8.07 (1Н, t, оJ = 8.0, Н-8);
7.93 (1Н, m, Н-9);
7.70 (1Н, t, оJ = 8.0, Н-2);
7.56 (1Н, d, оJ = 8.0, Н-4);
7.45 (1Н, d, оJ = 7.2, H-6');
7.31 (1Н, t, оJ = 7.2, H-4');
7.06 (1Н, t, оJ = 7.2, H-5');
6.62 (1Н, d, оJ = 8.0, H-3')
_______
* Indicated by point of inflection.
1554

positive charge, Thus the low field singlet at 10.60 ppm was assigned by us to the resonance of H-11 on the basis
of data obtained when studying the spectral behavior of the isomeric 5-oxo-5H,6H-isoquino-
[2,3-a]quinazolinium salts 8a,b [4, 5]. The characteristic region for absorption of aromatic protons of the type –
CH=N+ for compounds 8a,b was 10.9-12.00 ppm. The signals of the remaining aromatic protons of compound 7
were displaced towards low field by 0.3 ppm on average in comparison with the corresponding signals for the
initial salt 6 [1]. The greatest difference in chemical shifts is found for the H-10 proton (d, 8.62 ppm, ∆δ = 1.07),
which is in full agreement with the structure assigned to dehydrogenation product 7.
The dehydrogenation of proton salts of 6-benzyl-6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-ones
9a-c also takes place readily in nitrobenzene, and leads to 6-benzyl-13H-isoquino[3,2-b]quinazolin-13-ones
10a-c. This conversion is probably catalyzed by acid, since on using free bases of compounds 9a-c in the
reaction heavy resinification occurs and the yield of products of structure 10 is small. 6-Benzyl- and 6-(3-nitro-
benzyl)isoquinoquinazolines 10a,b were obtained as the free bases, but 6-(2-methylbenzyl)isoquinoquinazoline
10c as the hydrobromide. Evidently the higher stability of the proton salt of compound 10c in comparison with
the proton salts of compounds 10a,b may be explained by the donor effect of the 2-methylbenzyl substituent.
Nonetheless, the low stability of the proton salts of the dehydrogenation products 10 was somewhat unexpected,
since in the case of isoquino[2,3-a]quinazolines 8a such salts were completely stable [5].
Definite doubts as to the correctness of the structure assigned to the oxidation product of salt 9 were also
1
provoked by the picture of the absorption in the H NMR spectra. The singlet of the aliphatic protons of the
6-CH2Ar methylene group at 4.90-5.07 and the H-11 methine proton at 9.81-10.44 ppm may also be attributed to
the resonance of the corresponding groups in 6-(arylidene)-6,11-dihydro-13H-isoquino[3,2-b]quinazolin-
13-ones (11). The difference consisted of the position of the signal of the methine proton of the arylidene
residue, the resonance of which for compound 11 was observed at higher field (7.0-9.0 ppm) [8]. But since the
configuration of compound 11 has not been established we have not excluded the possibility of forming, on
oxidation of salts 9, the isomeric 6-arylidene derivatives with a configuration alternative to the condensation
product of isoquinoquinazoline 2 with benzaldehydes.
ε·103, mol-1·cm-1
nm
Fig. 1. UV spectra of compounds 7 (1), 8b (2), 10b (3), 10c (4), and 11·HBr (5)
(Ar = 4-O2NC6H4) in methanol.
1555

A final conclusion on the structures of compounds 10a-c as the products of dehydrogenation at positions
6 and 11 was made on the basis of an analysis of their electronic spectra. The absorption curves of solutions of
compounds 10b,c in methanol differed significantly in their shape from the absorption curves of 6-arylidene
derivatives 11 (see Fig. 1). In the UV spectra of compounds 10b,c absorption bands were observed with maxima
in the longer wave region with differences (∆λ >40 nm) exceeding in size those characteristic for cis and trans
isomers of olefins [11]. These bands have a clearly expressed fine structure which indicates the presence of a
more extended conjugation chain than for compounds 11. Such a phenomenon is characteristic of a conjugated
system formed from 7-12 double bonds [11]. An interesting result was also obtained on studying the electronic
spectra of N-methylisoquinoquinazoline perchlorates 8b and 7. The absorption curve of compound 7 differed
significantly in shape from the absorption curves of the dehydrogenation products 10 (see Fig. 1), which
indicates a different distribution of electron density in the molecule. Evidently in the case of the N-substituted
isoquinoquinazoline 7, as in the isomeric compound 8b, a structure is formed with a high degree of aromaticity
for the isoquinoquinazoline fragment, i.e. with retention of the aromatic sextet of the benzene ring of the
isoquinoline fragment, in difference to compound 10, which has an o-quinonoid structure.
In connection with the abovementioned it was also interesting to carry out the dehydrogenation of the
hydrohalides of 7-benzyl-7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones 12a-c which are isomeric to salts 9.
However on heating in nitrobenzene salts 12a-c readily rearranged into 9a-c hydrohalides, and the products of
the dehydrogenation reaction proved to be 6-benzyl-13H-isoquino[3,2-b]quinazolin-13-ones 10, obtained
previously also by thermal rearrangement in the absence of solvent [12].
It was noted previously that 6-methyl-5-oxo-5H,6H-isoquino[2,3-a]quinazolinium perchlorate 8b reacts
readily with nucleophilic reagents at position 12 with the formation of addition products or fission of the
isoquinoline ring [4]. Logically it was expected to display similar properties to the products of dehydrogenation
of an isoquinoquinazoline of linear structure, compounds 7 and 10. We studied the interaction of these
compounds with NaBH4. N-Methylisoquinoquinazoline perchlorate 7 reacts with NaBH4 in ethanol at room
temperature. The reaction occurs several minutes after adding the equivalent amount of reducing agent. The
mixture of products obtained by us contained only traces of the hydride anion addition product, 6-methyl-5,11-
1
dihydro-13H-isoquino[3,2-b]quinazolin-13-one (13, according to a H NMR spectrum of the mixture), obtained
previously [1] on interacting salt 6 with bases. 6-Benzylisoquinoquinazolines 10a,b proved to be inert to the
action of NaBH4 in alcohols (ethanol, methanol) both at room temperature and on heating. Use of acetic acid or
DMF as solvent led to a mixture of unidentified products. The interaction of salt 10c with NaBH4 in alcohols is
also accompanied by the formation of a complex mixture of products.
EXPERIMENTAL
Melting points were determined on a Boetius type heating instrument and are not corrected. The IR
1
spectra of compounds (KBr disks) were recorded on a Pye Unicam SP3-300 instrument. The H and 13C NMR
spectra were recorded on a Varian Mercury 400 instrument (400 and 100 MHz respectively), internal standard
was TMS. The UV spectra were recorded on a Specord M400 spectrophotometer in methanol. Mass spectra were
obtained by HPLC on an AGILENT/100 Series instrument (CI, acetonitrile, 0.05% formic acid). A check on the
progress of reactions and the purity of the compounds obtained was carried out with TLC on Silufol UV-254
plates.
6,11-Dihydro-13H-isoquino[3,2-b]quinazolin-13-one 2 was obtained by the method of [9], 5-methyl-
13-oxo-6,13-dihydro-11H-isoquino[3,2-b]quinazolin-5-ium perchlorate 6 as in [1], 6-benzyl-6,11-dihydro-
13H-isoquino[3,2-b]quinazolin-13-one hydrohalides 9a-c, and 7-benzyl-7,12-dihydro-5H-isoquino[2,3-a]-
quinazolin-5-one hydrohalides as in [12].
1556

11-Hydroxy-11H-isoquino[3,2-b]quinazoline-6,13-dione (4). Isoquino[3,2-b]quinazoline salt 2·HBr
(1-g, 3.04 mmol) was dissolved with heating in DMSO (5 ml). A 48% HBr solution (1 ml) was added and the
mixture boiled for 10 min. A precipitate formed during boiling. The mixture was cooled, the solid substance was
filtered off, and washed with a small quantity of DMSO and 2-propanol. Yield was 0.69 g (73%); mp 210-212°C
(DMF). IR spectrum (thin film), ν, cm-1: 3200 (OH), 1680 (br., C=O), 1595 (C=N), 1300 (C–O), 1050, 960, 767.
UV spectrum, λmax, nm (ε×10-3): 271 (61.62), 319 (51.68), 340 (52.67). Mass spectrum, m/z (Irel, %): 279 [M+1]+
1
o
(100), 261 [M+1–H2O]+ (10). H NMR spectrum, δ, ppm (J, Hz): 8.29 (1H, d, J = 8.0, H-7); 8.05 (1H, d,
oJ = 7.5, H-10); 7.92 (2H, m, H-2,4); 7.83 (1H, t, oJ = 7.5, H-3); 7.77 (1H, d, oJ = 7.5, H-1); 7.65 (2H, m, H-8,9);
7.37 (1H, br. s, OH); 7.15 (1H, s, H-11). C NMR spectrum, δ, ppm: 178.25 (C-6); 160.53 (C-13); 146.71 (C-
13
5a); 144.89 (C-4a); 140.13 (C-10a); 135.89, 135.84, 130.30, 129.97 (C-6a); 129.83, 129.70, 129.18, 127.39,
127.18, 122.49 (C-13a); 73.26 (C-11). Found, %: C 68.95; H 3.78; N 10.09. C16H10N2O3. Calculated, %:
C 69.06; H 3.62; N 10.07.
2-[(4-Oxo-3,4-dihydro-2-quinazolinyl)carbonyl]benzoic Acid Hydrobromide (5). A mixture of salt
2·HBr (1 g, 3.04 mmol) and 30% H2O2 (20 ml) was boiled for 2.5 h. In the process of boiling the solid substance
almost completely dissolved and a new solid precipitated. The mixture was cooled, the solid was filtered off,
washed with water and a small quantity of 2-propanol. Yield was 0.68 g (60%); mp 264-266oC (DMF). IR
spectrum (thin film), ν, cm-1: 3100 (br., OH, NH), 2960, 2500, 1700 (C=O), 1680 (C=O), 1650 (C=O), 1605
(C=N), 1440, 1190 (C–O), 765. 1H NMR spectrum, δ, ppm (J, Hz): 13.15 (1H, br., OH); 12.54 (1H, s, NH); 8.18
(1H, d, oJ = 8.0, H-3); 7.98 (1H, d, oJ = 8.0, H-6), 7.66-7.78 (4H, m, Ar-H); 7.56 (2H, m, Ar-H). Mass spectrum,
m/z (Irel, %): 295 [M+1]+ (100), 277 [M+1-H2O]+ (30). Found, %: Br 21.31; N 7.46. C16H10BrN2O4. Calculated,
%: Br 21.30; N 7.47.
5-Methyl-13-oxo-5H,13H-isoquino[3,2-b]quinazolinium Perchlorate (7). A suspension of 5-methyl-
isoquinoquinazoline perchlorate 6 (1 g, 2.76 mmol) in nitrobenzene (10 ml) was heated until all the solid had
dissolved. The mixture was boiled for a further10 min. After cooling, the precipitated solid was filtered off, and
washed with acetone.
6-Benzyl-13H-isoquino[3,2-b]quinazolin-13-one (10a). A. A suspension of 6-benzyl-6,11-dihydro-
13H-isoquino[3,2-b]quinazolin-13-one hydrochloride (9a) (1 g, 2.67 mmol) in nitrobenzene (10 ml) was heated
until all the solid substance had dissolved. The mixture was boiled for a further 5 min, and the solvent
evaporated in vacuum. 2-Propanol (15 ml) was added to the dark-red residual oil. The resulting solid was filtered
off and washed with 2-propanol.
B. The reaction was carried out analogously to method A using 7-benzyl-7,12-dihydro-5H-isoquino-
[2,3-a]quinazolin-5-one hydrobromide 12a (1 g, 2.67 mmol).
6-(3-Nitrobenzyl)-13H-isoquino[3,2-b]quinazolin-13-one (10b) was obtained by method A using the
appropriate 3-nitrobenzylisoquinoquinazoline hydrochloride 9b.
6-(2-Methylbenzyl)-13H-isoquino[3,2-b]quinazolin-13-one (10c) hydrobromide was obtained by
method A using the appropriate 2-methylbenzylisoquinoquinazoline hydrochloride 9c. After cooling the reaction
mixture, a solid was precipitated, which was filtered off, and washed with acetone.
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1.
L. M. Potikha and V. A. Kovtunenko, Khim. Geterotsikl. Soedin., 1698 (2007). [Chem. Heterocycl.
Comp., 43, 1454 (2007)].
2
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