Novel aspects of the reaction of 3-(benzimidazol-2-yl)-2-iminocoumarins with aromatic aldehydes

Article abstract of DOI:10.1023/B:COHC.0000028630.64934.8c

The reaction of 3-(benzimidazol-2-yl)-2-iminocoumarins with aromatic aldehydes has been studied. The condensation products 7-aryl-7H-benzo[4,5] imidazo[1,2-c]benzopyrano[3,2-e]pyrimidines or 3-(benzimidazol-2-yl)coumarins are formed depending on the nature of the substituent in the starting 2-iminocoumarin and aldehyde. In DMF medium, 7-aryl-7H-benzo[4,5]imidazo[1,2-c] benzopyrano[3,2-e]pyrimidines isomerize to the corresponding 7-aryl-14H-benzo[4,5]imidazo[1,2-c]benzopyrano-[3,2-e]pyrimidines. The effect of the substituent on the isomerization process has been studied and the reaction mechanisms are discussed.

Full text of DOI:10.1023/B:COHC.0000028630.64934.8c

Chemistry of Heterocyclic Compounds, Vol. 40, No. 3, 2004
NOVEL ASPECTS OF THE REACTION
OF 3-(BENZIMIDAZOL-2-YL)-2-IMINO-
COUMARINS WITH AROMATIC ALDEHYDES
N. Yu. Gorobets, V. V. Abakumov, A. V. Borisov, and V. M. Nikitchenko
The reaction of 3-(benzimidazol-2-yl)-2-iminocoumarins with aromatic aldehydes has been studied. The
condensation products 7-aryl-7H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidines or 3-(benz-
imidazol-2-yl)coumarins are formed depending on the nature of the substituent in the starting
2-iminocoumarin and aldehyde. In DMF medium, 7-aryl-7H-benzo[4,5]imidazo[1,2-c]benzopyrano-
[3,2-e]pyrimidines isomerize to the corresponding 7-aryl-14H-benzo[4,5]imidazo[1,2-c]benzopyrano-
[3,2-e]pyrimidines. The effect of the substituent on the isomerization process has been studied and the
reaction mechanisms are discussed.
Keywords: 7-aryl-7H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidine, 7-aryl-14H-benzo[4,5]-
imidazo[1,2-c]benzopyrano[3,2-e]pyrimidine, aromatic aldehyde, 3-(benzimidazol-2-yl)-2-imino-
coumarin, 3-(benzimidazol-2-yl)coumarin, substituent effect, isomerization, proton transfer,
equilibrium.
The considerable attention of investigators to 2-iminocoumarin derivatives is connected with their high
reactivity, potentially reacting both with electrophilic and with nucleophilic substituents [1-4]. Special interest in
this program has focused on reactions which form novel heterocyclic systems [5, 6].
In previous work [7] we reported the reaction of the 3-benzimidazol-2-yl-2-iminocoumarins 1a-c with an
excess of aromatic aldehydes 2b-f,k in refluxing n-propanol or n-butanol in the presence of catalytic amounts of
piperidine to give the 7-aryl-7H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidines 3a,i-k.
In several cases the condensation product could not be separated due to a side reaction involving the
hydrolysis of the 2-imino group to give 3-(benzimidazol-2-yl)coumarins [8, 9] (see Scheme 1).
With the aim of a detailed examination of the effect of the reaction conditions and nature of the
substituent on the course of the studied reaction for the 3-(benzimidazol-2-yl)-2-iminocoumarins and the
corresponding aromatic aldehydes in n-pentanol or n-butanol in the presence of pyridine, the 7-aryl-7H-
benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidines 3a-m were prepared (Table 1).
The effect of increasing the reaction temperature of the medium (exchanging n-butanol for n-pentanol)
in the case of the difficultly soluble starting unsubstituted 3-(benzimidazol-2-yl)-2-iminocoumarin 1a and the
methoxy derivative 1b was significant to decrease the time to carry out the reaction and to increase the yield,
however in the case of the 7-dialkyl derivatives 1c,d the use of n-butanol was optimal.
__________________________________________________________________________________________
V. N. Karazin National University, Kharkov 61077, Ukraine; e-mail: nic@univer.kharkov.ua. Translated
from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 410-420, March, 2004. Original article submitted
April 14, 2003.
334
0009-3122/04/4003-0334©2004 Plenum Publishing Corporation

Scheme 1
12
11
10
13
R2
N
N
4
5
CHO
14
1
4
3
6
7
2
9
N
N 8
R1
2a–d,f–k
R1
H
H
3
2
AlkOH
piperidine
O
NH
O
7
N
8
1
5
6
1a–d
R2
3a–m
2a–e
AlkOH
piperidine
N
N
R1
H
O
O
4a–c
6
7
8
N
1 a R1 = H, b R1 = 6-MeO, c R1 = 7-NEt2, d R1 =
2 a R2 = H, b R2 = 4-Cl, c R2 = 4-Br, d R2 = 4-OMe, e R2 = 4-NO2, f R2 = 4-NMe2, g R2 = 4-OH,
h R2 = 2-OH, i R2 = 4-OH-3-OMe, j R2 = 2-OH-3-OMe, k R2 = 2-OH-5-OMe; 3 a–e R1 = H,
a R2 = 4-NMe2, b R2 = 4-OH, c R2 = 2-OH, d R2 = 2-OH-3-OMe, e R2 = 4-OH-3-OMe,
f, g R1 = 2-MeO, f R2 = 2-OH, g R2 = 2-OH-3-OMe, h–k R1 = 3-NEt2, h R2 = H, i R2 = 4-Cl,
2
3
j R2 = 4-OCH3, k R2 = 2-OH-5-OMe, l, m R1 =
4 , l R2 = H, m R2 = 4-Br; 4 a R1 = H,
N
b R1 = 6-MeO, c R1 = 7-NEt2
The substituents in the starting 2-iminocoumarins 1a-d and the aromatic aldehydes proved to have a
significant effect on the reaction course. Hence in the case of the 2-iminocoumarins which contain a
dialkylamino group in position 7 (compounds 1c,d) the reaction occurs in good yield, even in n-butanol. For
completion of the reaction 15-60 min is sufficient, moreover it is possible to obtain the condensation products
with virtually all of the aromatic aldehydes 2a-d,k. However, the reaction of the 2-iminocoumarin 1c with
para-nitrobenzaldehyde 2e gave only the 3-benzimidazolylcoumarin 4c.
The reaction time increases to 2 h when using the unsubstituted 3-benzimidazol-2-yl-2-iminocoumarin
1a and the 6-methoxy derivative 1b. In these conditions, the condensation products (Table 1) are only formed
when using the aromatic aldehydes 2f-j with donor substituents in the aromatic ring. The presence of only one
para-methoxy group in the benzaldehyde 2d does not allow the condensation. The benzaldehydes 2a-e give the
3-benzimidazolylcoumarins 4a,b in almost quantitative yield.
In order to explain the effect reported above on the effect of the substituent one should bear in mind that
a donor substituent in position 7 of the 2-iminocoumarin increases the electron density both at the nitrogen atoms
of the benzimidazole and also on the 2-imino group nitrogen thus increasing the overall nucleophilicity of the
heterocyclic system. This makes possible the condensation of the 7-dialkylamino derivatives 1c,d with aromatic
aldehydes containing a different kind of substituent. Not so evident are the reasons why aromatic aldehydes
containing donor substituent take part in condensation with the 2-iminocoumarins 1a,b and those not containing
them don't.
335

TABLE 1. Characteristics of the Compounds 3b-h,l,m
Com-
pound
Empirical
formula
Yield,
%
Found N, %
Calculated N, %
IR spectrum, ν, cm-1
1Н NMR spectrum, δ, ppm (J, Hz)
——————
mp, °С
3b
3c
3d
C23H15N3O2
C23H15N3O2
C24H17N3O3
11.50
11.62
244-246 1452, 1520, 1560 (C=C); 1600, 1660
(C=N); 2830, 3008, 3060 (С–Н);
~3400 (O–H)
6.7 (2H, d, J = 8.5, 3',5'-H); 7.1-7.3 (8H, m, 2,3,4,7,9,11,2',6'-H);
7.5 (1H, td, J = 7.9, J = 1.5, 10-H); 7.6-7.8 (2H, m, 1,12-H);
8.3 (1Н, s, 14-H); 9.4 (1Н, s, OН)
52
71
67
11.50
11.66
257-259 1456, 1508, 1524 (C=C); 1600, 1672
(C=N); 2860, 3036 (С–Н);
6.7-6.8 (2H, m, 3',5'-H); 7.0-7.3 (7H, m, 2,3,4,9,11,2',6'-H);
7.4 (1Н, s, 7-H); 7.5 (1H, td, J = 7.9, J = 1.5, 10-H);
7.6-7.8 (2H, m, 1,12-H); 8.3 (1Н, s, 14-H); 9.7 (1Н, s, OН)
~3450 (O–H)
10.63
10.79
247-248 1452, 1492, 1528 (C=C); 1600, 1680
(C=N); 2830, 2912, 3056 (С–Н);
~3450 (O–H)
3.7 (3H, s, OMe); 6.7-6.8 (2Н, m, 4'- or 6',5'-H); 6.9 (1Н, dd, J = 7.6,
J = 2.1, 4'- or 6'-H); 7.0-7.3 (5Н, m, 2,3,4,9,11-H); 7.5 (1Н, s, 7-H);
7.5 (1H, td, J = 7.9, J = 1.5, 10-H); 7.6-7.8 (2Н, m, 1,12-H);
8.3 (1Н, s, 14-H); 8.9 (1Н, s, ОН)
3e
3f
C24H17N3O3
C24H17N3O3
10.63
10.69
261-262 1540, 1560, 1576 (C=C); 1604,1676
6.6-6.8 (2H, m, 5',6'-H); 7.0 (1H, d, J = 1.2, 2'-H);
71
58
(C=N);2932,3064 (С–Н) ; ~3300 (O–H) 7.0-7.3 (6H, m, 2,3,4,7,9,11-H); 7.5 (1H, td, J = 7.9, J = 1.5, 10-H);
7.6-7.8 (2H, m, 1,12-H); 8.3 (1Н, s, 14-H); 9.0 (1Н, s, OН)
10.63
10.50
272-273 1460, 1528, 1584 (C=C); 1604, 1672
(C=N); 2936, 2972, 3064 (С–Н);
~3450 (O–H)
3.8 (3H, s, OMe); 6.7-6.8 (2H, m, 3',5'-H);
7.0-7.3 (7H, m, 3,4,9,10,11,4',6'-H); 7.3 (1H, d, J = 2.7, 1-H);
7.4 (1Н, s, 7-H); 7.7 (1H, d, J = 7.9, 12-H); 8.2 (1Н, s, 14-H);
9.7 (1Н, s, ОН)
3g
3h
3 l
C25H19N3O4
C27H24N4O
C27H24N4O
9.88
289-290 1458, 1482, 1580 (C=C); 1623, 1667
(C=N); 2837, 2942, 2994, 3057 (С–Н);
~3450 (O–H)
3.73 (3H, s, 3'-OMe); 3.79 (3H, s, 2-OMe); 6.6-6.8 (2Н, m, 4'- or 6',5'-H);
6.9 (1H, dd, J = 7.6, J = 2.7, 4'- or 6'-H); 7.0–7.2 (5Н, m, 3,4,9,10,11-H);
7.3 (1Н, d, J = 2.7, 1-H); 7.4 (1Н, s, 7-H); 7.7 (1Н, d, J = 7.9, 12-H);
8.2 (1Н, s, 14-H); 8.9 (1Н, s, ОН)
79
66
72
10.06
13.32
13.24
261-263 1512, 1532, 1549 (C=C); 1612, 1668
(C=N); 2896, 2928, 2972, 3052,
3080 (С–Н)
1.1 (6H, t, J = 7.3, N(CH2CH3)2); 3.4 (4H, q, J = 7.3, N(CH2CH3)2);
6.4 (1H, d, J = 2.4, 4-H); 6.6 (1H, dd, J = 8.9, J = 2.4, 2-H);
7.0-7.2 (3H, m, 9,10,11-H); 7.2–7.4 (6H, m, 7,2',3',4',5',6'-H);
7.5 (1H, d, J = 8.9, 1-H); 7.6 (1H, d, J = 7.9, 12-H); 8.1 (1H, s, 14-H)
12.60
12.45
271-273 1542, 1564 (C=C); 1608, 1676 (C=N);
1.9 (4H, q, J = 6.0, N(CH2CH2CH2)2);
2932, 2952, 3004, 3024, 3044 (С–Н)
2.7 (4H, t, J = 6.0, N(CH2CH2CH2)2); 3.3 (4H, m, N(CH2CH2CH2)2);
7.0-7.2 (4H, m, 1,9,10,11-H); 7.2–7.4 (5H, m, 2',3',4',5',6'-H);
7.3 (1H, s, 7-H); 7.2-7.4 (5H, m, 2',3',4',5',6'-H);
7.6 (1H, d, J = 7.9, 12-H); 8.0 (1H, s, 14-H)
3m
C29H23BrN4O
10.70
10.63
>300
1452, 1528, 1568 (C=C); 1608, 1672
(C=N); 2848, 2892, 2932, 3048 (С–Н)
1.8 (4H, q, J = 6.0, N(CH2CH2CH2)2);
45
2.7 (4H, t, J = 6.0, N(CH2CH2CH2)2); 3.3 (N(CH2CH2CH2)2);
6.9-6.2 (4H, m, 1,9,10,11-H); 7.2 (1H, s, 7-H); 7.3 (2H, d, J = 8.2, 2',6'-H);
7.5 (2H, d, J = 8.2, 3',5'-H); 7.6 (1H, d, J = 7.9, 12-H); 8.0 (1H, s, 14-H)

When considering a possible reaction mechanism it should be noted that, while not appearing possible to
determine which of the nitrogen atoms (the nitrogen of the 2-imino group or one of the nitrogen atoms of the
benzimidazole ring) undergoes initial attack by the electrophilic carbonyl group of the aromatic aldehyde, a
necessary stage after the formation of the intermediate hemiaminal (a or b) is the fission of a molecule of water.
N
N
b
a
N
3
N
_
OH
Ar
..
H
or
1 + 2
C
C
–OH
–H
..
O
N
H
+
O
N
H
H
Ar
HO
In both possible transition states for the second stage, the methine carbon atom is surrounded by three
electron-acceptor atoms (the two nitrogen atoms and the oxygen atom) and must be markedly electron deficient.
Electron-donor substituents in the aryl radical can partially compensate for the deficit of electron density for this
atom, lowering the energy of the transition state for the irreversible terminal stage of the departure of a hydroxyl
group (typical of substitution reactions occurring via an SN1 mechanism).
In the reactions with the aldehydes 2a-e which give the 2-iminocoumarin hydrolysis products (the
3-benzimidazolylcoumarins 4a-c) it can be stated with confidence that the aldehyde participates in the hydrolysis
process. This is confirmed by the fact that a blank experiment (refluxing the 3-benzimidazolyl-2-iminocoumarin
1a in n-pentanol in the presence of piperidine for 10 h) shows no production of the corresponding coumarin 4a.
Evidently the function of the aldehyde is to form an aldimine.
When using DMF as reaction medium the unsubstituted 2-iminocoumarin 1a and
5-methoxysalicylaldehyde 2k give the isomer 7-(2-hydroxy-5-methoxyphenyl)-14H-benzo[4,5]imidazo[1,2-c]-
benzopyrano[3,2-e]pyrimidine (5a) but the para-dimethylaminobenzaldehyde 2f leads to a mixture of the
isomers 5b and 3a in the ratio 1:2 (method A).
12
11
13
N
10
H
H
14
1
4
9
2
3
2k
N 8
O
7
Me
O
N
5
6
N
HO
DMF
5a
N
piperidine
H
N
H
H
O
NH
3a
+
1a
N
2f
Method A
O
N
Me
N
5b
Me
These facts caused us to turn our investigation to the effect of solvent on the reaction course. It was
found that the 7H-derivatives 3a-k obtained in n-pentanol behaved differently, depending on the substituent,
when heated in DMF in the presence of piperidine. If the aryl radical contains hydroxy and methoxy groups
337

together, as occurs in compounds 3d,e,g, the isomerization occurs fully to give the 14H-isomers 5e,f,h
respectively (Table 2). Completion of this reaction needs about 2 h refluxing. If the aryl radical contains only
one donor substituent (a hydroxy or dimethylamino group, compounds 3a-c,f, method B) then after 2 h refluxing
in DMF in the presence of piperidine a new product is found in the reaction medium (TLC analysis) which does
not increase upon subsequent, prolonged reflux. Such behaviour points to the presence of an equilibrium
between the two isomers of 3a-c,f and 5b-d,g respectively.
N
H
H
N
Method B
N
R1
3d,e,g
3a–c,f
3h–k
N
R1
H
O
N
O
N
R2
5b–h
R2
5 b–f R1 = H, b R2 = 4-NMe2, c R2 = 4-OH, d R2 = 2-OH, e R2 = 2-OH-3-OMe,
f R2 = 4-OH-3-OMe, g, h R1 = 2-MeO, g R2 = 2-OH, h R2 = 2-OH-3-OMe
The 1H NMR spectra of the precipitates formed upon cooling the mixtures also supported the presence of
a mixture of the two isomers of 5b-d,g and 3a-c,f while in the case of the para-dimethylamino derivatives 5b
and 3a a mixture of the same composition (1:2, method B) is formed as in the direct reaction of
para-dimethylaminobenzaldehyde with 2-iminocoumarin 1a in DMF (method A). The pure 14H-derivatives
5d,g can be prepared in good yield by a double recrystallization of the equilibrium mixture from DMF (Table 2).
In the case of the 3-diethylamino derivatives 3h-k the isomerization is not observed.
Basic catalysis of the isomerization infers separation of a methine proton. In view of the absence of
isomerization in alcohol medium it can be proposed that the anion is unstable under these conditions and can be
rapidly protonated. On the other hand, in the aprotic dimethylformamide the anion is more stable and can exist
for quite a long time thus bringing about a proton addition at position 14 and hence we were able to separate the
thermodynamically more stable isomer or to observe the equilibrium. Based on such a mechanism we favored
the proposal that acid may also serve as catalyst. In fact, in the protic n-butanol in the presence of sulfuric acid
an equilibrium between the isomers of 5b and 3a is also observed but with a rather different ratio of isomers
(3:4, method B). The position of the equilibrium depends on the relative thermodynamic stability of the isomers
and the properties of the medium, hence the nature of the substituent in the coumarin and aryl fragments
determines the ability of the 7H-derivatives 3a-k to undergo isomerization. The presence in the 7H-derivatives
of a donor substituent in position 3 (compounds 3h-k) evidently stabilizes the 7H-isomer due to conjugation of
the dimethylamino group with the acceptor benzimidazole and iminolactone heterocyclic system fragments
hence these derivatives do not isomerize. On the other hand, donor substituents in the aryl radical stabilize the
14H-isomer thanks to their conjugation with the acceptor pyrimidine ring.
The 1H NMR spectra of the synthesized compounds fully agree with the structure proposed (see Tables 1
and 2 and also [7]). The singlet for the methine proton at position 7 in the 7H-derivatives 3a-m appears in the
aromatic proton resonance region (7.0-7.5 ppm) but, none the less, its chemical shift can be identified in the
majority of cases. To a significant extent the position of this signal depends on the nature of the substituent in the
coumarin and aryl fragments of the molecules (see Table 1). The chemical shift of the singlet for the proton at
position 14 depends only on the nature of the substituent R1. This signal is subsequently shifted to high field
with an increase in the donor strength of the substituent R1 when going from the compounds unsubstituted in the
coumarin fragment of the compounds 3b-e to the julolidine derivatives 3l,m. The multiplet for the ABCD spin
system of the four benzimidazole protons is seen at 7.0-7.8 ppm. In several cases the signals for the protons in
positions 10 and 12 appear, respectively, as a triplet of doublets at 7.5 and a doublet at 7.6-7.7 ppm with the
338

TABLE 2. Characteristics of the Compounds 5a,d-h
Com-
pound
Empirical
formula
Yield,
%
Found N, %
Calculated N, %
IR spectrum, ν, cm-1
1Н NMR spectrum, δ, ppm. (J, Hz)
——————
mp, °С
5a
5d
5e
5f
C24H17N3O3
C23H15N3O2
C24H17N3O3
C24H17N3O3
C24H17N3O3
10.63
10.75
281-283
1456, 1500, 1572 (C=C); 1636, 1667
(C=N); 2837, 2960, 3004, 3040 (С–Н);
~3400 (O–H)
3.8 (3H, s, OMe); 4.3 (2H, s, CH2); 6.7 (1H, d, J = 7.9, 9-H);
7.0-7.3 (6Н, m, 1,2,4,10,3',6'-H); 7.3 (1H, m, 3-H);
7.4-7.5 (2H, m, 11,4'-H); 7.8 (1Н, d, J = 7.9, 12-Н); 9.5 (1Н, s, ОН)
48
63
55
70
60
11.50
11.38
291-293
269-271
300-302
288-290
1454, 1560, 1584 (C=C); 1598, 1630
(C=N); 2848, 2910, 3018, 3050 (С–Н);
~3450 (O–H)
4.3 (2H, s, CH2); 6.7 (1H, d, J = 7.9, 9-H);
6.9-7.7 (10Н, m, 1,2,3,4,10,11,3',4',5',6'-H);
7.8 (1Н, d, J = 7.9, 12-Н); 10.1 (1Н, s, ОН)
10.63
10.65
1455, 1488, 1560 (C=C); 1622, 1648
(C=N); 2832, 2925, 2950 (С–Н);
~3550 (O–H)
3.9 (3H, s, OMe); 4.3 (2H, s, CH2); 6.6 (1H, d, J = 7.9, 9-H);
7.0-7.3 (5Н, m, 2,4,10,5',4'- or 6'-H); 7.2-7.4 (2H, m, 3, 4'- or 6'-H);
7.4-7.5 (2H, m, 1,11-H); 7.8 (1Н, d, J = 7.9, 12-Н); 9.3 (1Н, s, ОН)
10.63
10.48
1491, 1573, 1590 (C=C); 1602, 1632
(C=N); 2828, 2890, 2955 (С–Н);
~3450 (O–H)
3.8 (3H, s, OMe); 4.2 (2H, s, CH2); 6.8 (1H, d, J = 7.9, 9-H);
6.7-7.5 (9H, m, 1,2,3,4,10,11,2',5',6'-H); 7.7 (1Н, d, J = 7.9, 12-Н);
9.7 (1Н, s, ОН)
5g
10.63
10.54
1490, 1570, 1590 (C=C); 1604, 1642
(C=N); 2832, 2929, 3006 (С–Н);
~3450 (O–H)
3.8 (3H, s, OMe); 4.3 (2H, s, CH2); 6.6 (1H, d, J = 7.9, 9-H);
6.8 (1Н, dd, J = 8.9, J = 2.7, 3-H); 6.9-7.2 (5Н, m, 1,4,10,3',5'-H);
7.4 (1Н, t, J = 7.9, 11-H); 7.5-7.6 (2H, m, 4',6'-H);
7.8 (1Н, d, J = 7.9, 12-Н); 10.0 (1Н, s, ОН)
5h
C25H19N3O4
9.88
9.95
299-302
1455, 1487, 1582 (C=C); 1628, 1640
(C=N); 2828, 2890, 2930, 2982 (С–Н);
~3450 (O–H)
3.8 (3H, s, 2-OMe); 3.9 (3H, s, 3'-OMe); 4.3 (2H, s, CH2);
6.6 (1H, d, J = 7.9, 9-H); 6.9 (1Н, dd, J = 8.9, J = 2.7, 3-H);
7.0-7.2 (5Н, m, 1,4,10,4'- or 6',5'-H);
45
7.3 (1Н, dd, J = 6.4, J = 3.1, 4'- or 6'-H); 7.4 (1Н, t, J = 7.9, 11-H);
7.8 (1Н, d, J = 7.9, 12-Н); 9.3 (1Н, s, ОН)

Fig. 1. Resulting calculated structures for compounds 3g (a) and 5h (b) using the method of molecular
mechanics (MM+).
single large spin-spin coupling of J = 7.9 Hz. The signal for the methylene group closest to the nitrogen in the
julolidine derivatives 3l,m is partially (for compound 3l) or fully (for 3m) obscured by the signal for the water in
the DMSO-d6.
1
In the H NMR spectra of the 14H-derivatives 5a-h a singlet is observed in the region 4.2-4.3 ppm for
the two protons of the methylene group. Additionally, the characteristic signal for the proton at position 14 in the
range 8.2-8.3 ppm is not observed. For a precise and proven assignment of the aromatic proton signals in the
spectrum of the derivative 5h we have used the COSY 2D 1H NMR spectroscopic method. The presence of three
cross peaks for the doublet at 6.6 ppm shows that this signal lies at an anomalously high field position for a
benzimidazole [10], none the less it is assigned to position 9. Such a shift is attributable to the magnetic
anisotropy of the aryl radical in position 7. The fact that this proton is found over the plane of the aryl radical in
position 7 in the molecule 5h (in contrast to the isomer 3g) is confirmed by structural calculations made by
molecular mechanics (Figure 1).
Strong bands for a C=N bond are observed in IR spectra of the 7H-derivatives 3b-h,l,m in the region
1600-1680 cm-1. The spectra of the 14H-isomers 5a,d-h show two C=N vibrations at 1598-1667 cm-1. In both
series of isomers bands of varying intensity for the C=C bonds in the aromatic and heterocyclic rings are found
in the range 1452-1590 cm-1. C–H Alkyl bond bands are seen at 2828-2972 cm-1 and weak bands for the
aromatic and heterocyclic C–H vibrations appear in characteristic regions of the spectrum at 2994-3080 cm-1 (see
Tables 1 and 2).
Hence the reactivity of 3-(benzimidazol-2-yl)-2-iminocoumarins with aromatic aldehydes is controlled
by the nature of the substituent and the conditions for carrying out the reaction.
The 7H-derivatives 3h-j,l,m contain a dialkylamino group at position 3 and are high efficiency
fluorophores. As was shown in our work [11], they can be used as laser dyes, the generation energy parameters
of which exceed the corresponding value for the structurally similar laser dye coumarin 7 (compound 4c).
EXPERIMENTAL
IR spectra were measured for KBr tables on a Specord M82 spectrophotometer in the range 400 to
1
4000 cm-1 and H NMR spectra on a Varian Mercury 200 (200 MHz) instrument using DMSO-d6 solvent and
TMS internal standard. The purity of all of the products was monitored by TLC using Silufol UV-254 plates and
with ethyl acetate as eluent.
340

7-Aryl-7H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidine (3a-m) (General Method). A
mixture of the 3-(benzimidazol-2-yl)-2-iminocoumarin 1a-d (3.5 mmol) and the aromatic aldehyde 2a-k
(5 mmol) in n-pentanol (10-15 ml) (or the same volume of n-butanol for the 7-dialkylamino derivatives 1c,d)
was heated to reflux, piperidine (3-4 drops) was added, and the product was refluxed for 2 h, cooled, and left
overnight. The precipitated solid was filtered off, washed with ethanol, and recrystallized from n-butanol or a
mixture of n-butanol and DMF (see Table 1).
7-(Hydroxy-5-methoxyphenyl)-14H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidine (5a). A
mixture of the 3-(benzimidazol-2-yl)-2-iminocoumarin 1a (2 mmol) and 5-methoxysalicylaldehyde 2k (3 mmol)
in DMF (3 ml) was heated to reflux, piperidine (4 drops) added, refluxed for 3 h, cooled, and left overnight. The
precipitated solid was filtered off, washed with ethanol, and recrystallized from DMF (Table 2).
Equilibrium Mixture of 7-(4-Dimethylaminophenyl)-14H-benzo[4,5]imidazo[1,2-c]benzopyrano-
[3,2-e]-pyrimidine (5b) and 7-(4-Dimethylaminophenyl)-7H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]-
pyrimidine (3a). A.
A
mixture of 3-(benzimidazol-2-yl)-2-coumarin 1a (2 mmol) and para-
dimethylaminobenzaldehyde 2f (3 mmol) in DMF (3 ml) was heated to reflux, piperidine (4 drops) added,
refluxed for 2 h, cooled, and left overnight. The precipitated solid was filtered off and washed with ethanol.
1
According to H NMR data the mixture contains the products 5b and 3a in the ratio of about 1:2. The
equilibrium mixture for 5c and 3b was obtained similarly (about 3:5). Recrystallization from DMF and/or AcOH
did not lead to the separation of a single product.
B. Piperidine (4 drops) was added to 7-(4-dimethylamino)-7H-benzo[4,5]imidazo[1,2-c]benzopyrano-
[3,2-e]pyrimidine 3a (2 mmol) in DMF (3 ml) and the product was refluxed for 2 h, cooled, and left overnight.
1
The precipitated solid was filtered off and washed with ethanol. According to the H NMR data the mixture
contains the products 5b and 3a in the ratio of about 1:2.
C. Freshly prepared H2SO4 solution in n-butanol (5%, 4 drops) was added to 7-(4-dimethylamino)-7H-
benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidine 3a (2 mmol) in n-butanol (8 ml), and the product was
refluxed for 2 h, cooled, and left overnight. The precipitated solid was filtered off and washed with ethanol.
According to the 1H NMR data the mixture contains the products 5b and 3a in the ratio of about 3: 4.
7-Aryl-14H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]pyrimidine (5d-h) (General Method).
Piperidine (4 drops) was added to the 7-aryl-7H-benzo[4,5]imidazo[1,2-c]benzopyrano[3,2-e]-pyrimidine 3c-g
(2 mmol) in DMF (3 ml) and the product was refluxed for 2 h, cooled, and left overnight. The precipitated solid
was filtered off, washed with ethanol, and recrystallized from a mixture of n-butanol and DMF. In the case of the
ortho-hydroxy derivatives 3c and 3f the initially formed precipitate is a mixture of the isomers 5d and 3c or 5g
and 3f respectively. A double recrystallization of these precipitates from DMF led to separation of the products
5d and 5g respectively (see Table 2).
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