Chemistry of 3-hetarylcoumarins. 1. 3-(2-Benzazolyl)coumarins

Article abstract of DOI:10.1023/A:1012704121345

The reaction of substituted salicylaldehydes with 2-benzimidazolyl- and 2-benzothiazolylacetonitriles gives the corresponding 3-hetarylcoumarins. The alkylation, acylation, and aminomethylation reactions of these 7-hydroxy-substituted hetero isoflavonoid analogs has been studied.

Full text of DOI:10.1023/A:1012704121345

Chemistry of Heterocyclic Compounds, Vol. 37, No. 8, 2001
CHEMISTRY OF 3-HETARYLCOUMARINS.
1. 3-(2-BENZAZOLYL)COUMARINS
O. V. Khilya, M. S. Frasinyuk, A. V. Turov, and V. P. Khilya
The reaction of substituted salicylaldehydes with 2-benzimidazolyl- and 2-benzothiazolylacetonitriles
gives the corresponding 3-hetarylcoumarins. The alkylation, acylation, and aminomethylation reactions
of these 7-hydroxy-substituted hetero isoflavonoid analogs has been studied.
Keywords:
alkoxycoumarins,
8-aminomethyl-7-hydroxycoumarins,
acyloxycoumarins,
3-(2-benzimidazolyl)coumarin, 3-(2-benzothiazolyl)coumarin.
In recent times there have been broad developments in investigations of both the synthesis and the study
of the chemical properties of coumarins which have valuable pharmacological activity. Hence,
4-hydroxycoumarin derivatives are anticoagulants (the drugs syncoumar (acenocoumarol) and neodicoumarin)
and a series of coumarins find use in laser spectroscopy [1, 2]. Amongst compounds possessing valuable optical
properties are the 3-hetarylcoumarins containing 2-benzimidazole, 2-benzothiazole, 2-benzoxazole, 2-thiazole,
and 4-thiazole residues, the latter having the greatest interest.
The following methods have been developed for the synthesis of 3-benzazolylcoumarins. Reaction of
substituted salicylaldehydes with 2-benzazolylacetonitriles of benzazolylacetic acid esters in the presence of
base [3-11] as well as with 2-benzazolylacetonitrile perchlorates [12] and subsequent acid hydrolysis of the
2-iminocoumarins formed; the reaction of 2-iminocoumarin-3-carboxyimides with o-aminothiophenol,
o-aminophenol, and o-phenylenediamine [13]; the condensation of methyl coumarin-3-carboxylate with
o-phenylenediamines in polyphosphoric acid [14]; the cyclodehydrogenation of coumarin-3-thiocarboxamides
[15]; the reaction of 4-hydroxy-3-formylcoumarin and o-aminothiophenol to form 3-(2-benzothiazolyl)-4-
hydroxycoumarin [16]; and the photochemical reaction of 3-iodo-4-methyl-7-diethylaminocoumarin with
benzimidazole [17].
However, despite the numerous publications concerning the synthesis and investigation of the
spectroscopic properties of 3-benzazolylcoumarins, only their oxidative cyanation [18], acylation of
3-(2-benzazolyl)-7-hydroxycoumarins using carboxylic acid anhydrides and chlorides in dimethylformamide,
and also their reaction with chlorosulfonic acid and phosphorus oxychloride in pyridine [19] have been reported.
In order to extend our work on the chemistry of 3-benzazolylbenzopyrones and to add to the previously
prepared benzimidazole [20] and benzothiazole [21] isoflavone analogs we have carried out the synthesis of the
isomeric 3-(2-benzimidazolyl)- and 3-(2-benzothiazolyl)coumarins 1, 2, and 3 respectively. In contrast to the
oxadiazolyl coumarin derivatives [22], the condensation of the 5-chloro-, 5-bromo-, 5-nitro-, 3,5-dichloro-,
4-hydroxy-, and 3-methoxysalicylaldehydes with 2-benzimidazolyl(benzothiazolyl)acetonitriles permits the
preparation of the substituted 3-hetarylcoumarins 1a-f to 3a-f in yields which are sometimes close to
__________________________________________________________________________________________
Taras Shevchenko University, Kiev 252033, Ukraine; e-mail: mfras@i.kiev.ua. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1120-1129, August, 2001. Original article submitted
July 22, 1999; revision submitted September 20, 2000.
0009-3122/01/3708-1029$25.00©2001 Plenum Publishing Corporation
1029

quantitative. We have used piperidine as the base, whereas the authors of [3] employed ammonium acetate. The
products obtained were high melting, colored materials which were difficultly soluble in organic solvents,
insoluble in water, and poorly soluble upon heating in mineral acids (Table 1).
R 1
R1
R2
OH
R2
O
O
X
N
X
+
O
3
3
N
CN
R
R
1a–f – 3a–f
RO
HO
RCOO
5e, 6e–g
4a, 5a–c – 6a–c
1e–3e
Y
NR2
N
HO
HO
CH3SO2O
5d, 6d
10a–c – 12a–c
7a,b–9a,b
1, 4, 7, 10 X = NH; 2, 5, 8, 11 X = NCH3; 3, 6, 9, 12 X = S. 1-3 R1 = R2 = H, a R3 = Cl;
b R3 = Br, c R3 = NO2, d R1 = R3 =Cl, R2 = H, e R1 = R3 = H, R2 = OH, f R1 = OCH3, R2 = R3 = H.
4-6 a,e R = CH3, b R = 2-furyl, c R = C6H4OCH3-4, f R = CH2COOC2H5, g R = CH2COOH;
7-9 a R = CH3, b R = C2H5, 10-12 a Y = O, b Y = CH2, c Y = NCH3
1
Conformation of the formation of the -pyrone ring comes from the H NMR spectra of these
α
compounds measured in DMSO-d6. Hence the lowest field region (8.4-9.3 ppm) shows a singlet signal for the
proton in position 4 of the coumarin system and signals for the protons of the benzazole fragment which appear
as multiplets in the range 7.2-8.1 ppm. The signals for the protons of ring A of the coumarin in compounds
1a-c,e to 3a-c, e are characteristic for a 1,2,4-trisubstituted aromatic system (Table 2).
The signals for the protons in positions 5, 6, and 7 of the 8-methoxycoumarins 1f-3f appear, in most
cases, as multiplets which are found within the region of the signals of the benzazole fragment and hence their
exact assignment is impossible (the spectra of these compounds are presented in the Experimental section).
The obtained 7-hydroxy substituted 3-benzazolylcoumarins 1e-3e are readily acylated using acetic
anhydride and also the acid chlorides of 2-furancarboxylic, 4-methoxybenzoic, and methanesulfonic acids. The
reactions occur smoothly in pyridine to form the 7-acyloxy derivatives 4a, 5a-c, and 6a-c and the
7-mesyloxycoumarins 5d, 6d. In contrast to the results presented in [3], the coumarin 1e and acetic anhydride
gave only the O-acetyl derivative 4a.
The signal for a 7-OH group is absent in the 1H NMR spectra of the acyl derivatives 4a, 5a-d, and 6a-d
and, instead, there are observed the signals for the acyl substituents or the mesyl group. Due to a paramagnetic
shift, the signals of the protons in positions 6 and 8 of the coumarin fragment are shifted into the region of the
benzazole signals and this markedly complicates the interpretation of the spectra of these compounds (see
Experimental section).
1030

TABLE 1. Characteristics of 3-(2-Benzazolyl)coumarins 1-12
Found, %
——————
Com-
pound
Empirical
formula
Calculated, %
mp, °С
Yield, %
N
3
Cl or Br
4
S
5
1
1a
1b
1c
1d
1e
1f
2
6
7
C16H9ClN2O2
C16H9BrN2O2
C16H9N3O4
10.17
9.44
12.86*
11.95*
271-272
279-281
330-331
318-319
>360
44
46
81
79
97
92
99
82
73
69
97
65
96
95
94
97
98
95
65
70
80
65
63
55
80
76
70
85
76
78
74
8.51
23.32*2
23.46*2
8.21
13.88
13.68
C16H8Cl2N2O2
C16H10N2O3
C17H12N2O3
C17H11ClN2O2
C17H11BrN2O2
C17H11N3O4
C17H10Cl2N2O2
C17H12N2O3
C18H14N2O3
C16H8ClNO2S
C16H8BrNO2S
C16H8N2O4S
C16H7Cl2NO2S
C16H9NO3S
C17H11NO3S
C18H12N2O4
C19H14N2O4
C22H14N2O5
C25H18N2O5
C18H14N2O5S
C18H14N2O3
C18H11NO4S
C21H11NO5S
C24H15NO5S
C17H11NO5S2
C17H11NO3S
C20H15NO5S
C18H11NO5S
8.65
21.04*
21.41*
8.46
10.40
10.07
9.72
280-282
272-273
262-264
282-284
266-267
331-333*5
282-284
239-241
266-269*3
303-304*4
250-252
295
9.58
8.80
9.01
11.22*
11.41*
2a
2b
2c
2d
2e
2f
8.08
22.94*2
22.54*2
7.89
12.67
13.08
8.37
20.18*
20.54*
8.12
9.50
9.58
9.33
9.15
4.32
4.46
11.342*
11.30*
10.10
10.22
3a
3b
3c
3d
3e
3f
4.11
22.15
9.10
3.91
22.31*
8.95
8.55
8.64
10.12
9.89
4.29
20.34*
20.36*
9.38
4.02
9.21
4.50
4.74
10.83
10.86
4.55
10.50
250-251
268-270*6
238-240
252-255
275-277
217-218
236-237
282-284
253-255
255-256
249-251
242-244
206-208
>300
4.53
10.57
8.50
8.75
4a
5a
5b
5c
5d
5e
6a
6b
6c
6d
6e
6f
8.12
8.38
7.14
7.25
6.80
6.57
7.45
7.56
8.70
8.66
9.23
9.15
4.12
4.15
9.35
9.50
3.44
8.30
3.60
8.23
3.04
3.26
7.78
7.47
3.62
17.31
3.75
17.17
4.58
4.53
10.55
10.37
3.55
8.50
3.67
8.41
3.80
3.96
8.92
9.07
6g
1031

TABLE 1 (continued)
1
2
3
4
5
6
7
C19H17N3O3
C21H21N3O3
C20H19N3O3
C22H23N3O3
C19H16N2O3S
C21H20N2O3S
C21H19N3O4
C22H21N3O3
C22H22N4O3
C22H21N3O4
C23H23N3O3
C23H24N4O3
C21H18N2O4S
C22H20N2O3S
C22H21N3O3S
13.07
12.53
284-286
238-240
227-228
186-188
260
80
45
90
55
95
70
88
75
72
78
70
58
90
82
81
7a
7b
8a
8b
9a
9b
11.43
11.56
11.96
12.03
11.25
11.13
7.90
7.95
8.97
9.10
7.52
8.28
175-177
272-274
269-270
254-257
257-259
228-229
184-186
258-260
250-251
228-230
7.36
8.43
10.95
11.13
10a
10b
10c
11a
11b
11c
12a
12b
12c
11.37
11.19
14.21
14.35
10.68
10.74
10.92
10.79
13.93
13.85
7.25
7.10
8.32
8.13
7.28
8.07
7.14
8.17
10.36
10.31
7.76
7.87
_______
* Cl, %.
*2 Br, %.
*4 260°C [3]; 305-306°C [10].
*5 295°C [3].
*3 267-269°C [10].
*6 270-272°C [19].
We have also studied the possible alkylation of the 7-hydroxycoumarins 2e, 3e. Prolonged refluxing of
the latter with dimethylsulfate in acetone in the presence of excess potassium carbonate gives the
7-methoxycoumarins 5e, 6e and coumarin 3e and ethyl bromoacetate yields the 7-carbethoxymethyl-substituted
6f under similar conditions. Hydrolysis of the latter in acetic acid in the presence of sulfuric acid then gives the
7-coumaryloxyacetic acid 6g.
In a continuation of work on the aminomethylation of 3-benzazolylbenzopyrones we have carried out
the synthesis of the Mannich bases 7a,b-9a,b and 10a-c to 12a-c, which are isomeric to the previously obtained
chromone derivatives [23]. As in the case of the 3-benzazolylchromones, the aminomethylation of the coumarin
nucleus does not occur when using formalin and a secondary amine in organic solvents or in water. The
lowering of the reactivity towards electrophilic substitution of the coumarin system can be explained in terms of
the effect of the electron-accepting benzazole substituent in position 3 of the pyrone ring. When carrying out the
Mannich reaction with the amine hydrochlorides in alcohol or acetic acid, the formation of the aminomethyl
derivatives is again not observed. The presence of acid causes protonation of the nitrogen atom of the benzazole
substituent and this hinders even further the electrophilic attack at the coumarin nucleus. In this connection we
have attempted to use aminals to carry out the aminomethylation. The reaction with these occurs in neutral or
weakly basic medium and so the effect of the benzazole nucleus on the activity of the coumarin system is not so
significant. In most cases the aminals can be used as efficient media for carrying out the aminomethylation of
the benzopyrone system. Hence the 3-(2-benzazolyl)-7-hydroxycoumarins 1e-3e have two reactive centers for
1032

TABLE 2. 1H NMR Spectra of 3-(2-Benzazolyl)coumarins 1a-e to 3a-e, 5e,
and 6e-g, , ppm
δ
Com-
Coumarin residue
3-Het*2
4-and 7-Н, m 5- and 6-Н, m
pound
4-Н, s
5-H
6-H
7-H / R
8-H
9.08
9.08
9.19
9.07
9.02
8.09 *3
8.24 *3
8.88 *3
8.08, s
7.83 *5
—
—
7.70 *4
8.85 *4
8.38 *4
7.97, s
7.57 *5
7.47 *5
7.46 *5
—
7.65
7.71
7.64
7.67
7.65
7.21
7.25
7.19
7.21
7.20
1a
1b
1c
1d
1e
—
—
6.90 *4
12.36
6.85 *3
(br. s, ОН)
8.58
8.51
8.72
8.54
8.40
8.04 *3
8.14 *3
8.90 *3
8.06, s
7.65 *5
—
—
—
7.80 *4
7.88 *4
8.50 *4
7.98, s
7.58 *5
7.48 *5
7.74 *5
—
7.75
7.67
7.68
7.66
7.65
7.37
7.32
7.34
7.32
7.30
2a
2b
2c
2d
2e
—
6.87 *4
10.74
6.84 *3
(br. s, ОН)
9.07
9.14
9.33
8.98
9.12
8.08 *3
8.28 *3
9.00 *3
8.0, c
—
—
—
7.67 *4
7.86 *4
8.46 *4
7.82, s
7.50 *5
7.46 *5
7.75 *5
—
8.08
8.12
8.14
8.0
7.53
7.51
7.53
7.46
7.48
3a
3b
3c
3d
3e
—
8.06 *5
6.90 *4
11.07
6.85 *3
7.88
(br. s, ОН)
8.68
9.06
7.89 *5
7.90 *5
7.10 *4
6.98 *4
3.94
7.17 *3
7.05 *3
7.80
8.05
7.49
7.50
5e
6e
(3H, s, ОCH3)
3.87
(3H, s, ОCH3)
9.18
8.01 *5
7.11 *4
1.26
(3Н, t, СН3*6);
4.29
7.15 *3
8.06
7.52
6f
(2Н, q, СН2О*6);
4.99
(2Н, s, ОСН2).
9.10
7.92 *5
6.92 *4
4.43
7.97 *3
7.47
8.08
6g
(2Н, s, ОСН2)
_______
* The exact positions of the 7-OH group of the coumarin cycle and the NH
group proton signals cannot be given due to their considerable broadening.
*2 In compounds 2a-e, 5e the signal for the protons of the NCH3 group
appears as a three-proton singlet in the region 3.76-3.92 ppm.
*3 d, 4J = 2.5-3.0 Hz.
*4 dd, 4J , 3J =8.5-9.1, 2.5-3.0 Hz.
*5 d, 3J = 8.5-9.1 Hz.
*6 3J = 7.2 Hz.
electrophilic substitution and these are positions 6 and 8 of the coumarin nucleus. In the case of compound 3e
(according to TLC and 1H NMR data) it was found that carrying out the aminomethylation with a marked excess
of bis(dimethylamino)methane (10-15 times) formed both the 8-dimethylaminomethyl and also the
6,8-bisdimethylaminomethyl derivatives. Attempts to prepare only the latter did not end successfully both with
an excess of the aminomethylating agent and with a longer reaction time (20-30 h). On the other hand, the use of
a slight excess of the aminal (10-15%) led to the exclusive formation of the 8-aminomethyl derivative. The
1H NMR spectra of the products 7a-b to 12a-b were in agreement and showed signals for the protons at
positions 5 and 6 which appeared as doublets with 3J = 8.5-9.0 Hz (Table 3).
1033

1
TABLE 3. H NMR Spectra of the Mannich Bases 7a,b to 9a,b, and 10a-c
to 12a-c, , ppm*
δ
Coumarin residue
Het*2
Com
5-H,
6-Н,
4-Н,
8-CH2,
4- and
5- and
NR2R3
3J = 8.5-
9.1 Hz
3J = 8.5-
pound
s
s
7-Н, m
6-Н, m
9.1 Hz
8.96
8.93
7.70
7.67
6.70
6.70
4.08
4.15
2.49 (6Н, s 2NCH3)
7.63
7.65
7.17
7.17
7а
7b
2.80 (4Н, q, 2NCH2*3),
1.15 (6Н, t, 2CH3*3)
8.36
8.35
7.62
7.62
6.72
6.70
4.07
4.15
2.45 (6Н, s 2NCH3)
7.65
7.65
7.27
7.30
8a
8b
2.75 (4Н, q, 2NCH2*3),
1.10 (6Н, t, 2CH3*3)
8.95
8.94
7.67
7.64
6.57
6.55
4.13
4.17
2.59 (6Н, s N(CH3)2)
8.00
8.11
7.45
7.44
9a
9b
2.92 (4Н, q, 2NCH2*3),
1.19 (6Н, t, 2CH3*3)
8.99
9.00
9.01
7.78
7.73
7.73
6.88
6.87
6.88
3.90
4.08
4.0
2.62 (4Н, m, 2NCH2),
3.65 (4Н, m, 2OCH2)
7.65
7.65
7.64
7.20
7.20
7.16
10a
10b
10c
2.73 (4Н, m, 2NCH2),
1.56 (6Н, m, 3CH2)
2.41 (4Н, m, 2NCH2),
2.65 (4Н, m, 2NCH2),
2.18 (3Н, s, NCH3)
8.44
8.36
8.46
7.68
7.62
7.63
6.88
6.87
6.82
3.99
4.05
4.0
2.56 (4Н, m, 2NCH2),
7.64
7.65
7.60
7.28
7.30
7.25
11a
11b
11c
3.64 (4Н, m, 2OCH2)
2.66 (4Н, m, 2NCH2),
1.55 (6Н, m, 3CH2)
2.40 (4Н, m, 2NCH2),
2.64 (4Н, m, 2NCH2),
2.18 (3Н, s, NCH3)
9.12
8.99
9.02
7.86
7.72
7.77
6.90
6.69
6.80
3.93
4.09
3.98
2.60 (4Н, m, 2NCH2),
8.09
8.07
8.06
7.49
7.46
7.46
12a
12b
12c
3.65 (4Н, m, 2OCH2)
2.79 (4Н, m, 2NCH2),
1.58 (6Н, m, 3CH2)
2.42 (4Н, m, 2NCH2),
2.68 (4Н, m, 2NCH2),
2.20 (3Н, s, NCH3)
_______
* The exact positions of the 7-OH and NH groups cannot be given due to
their considerable broadening.
*2 In compounds 8a,b, 11a-c the signal for the protons of the NCH3 groups
appears as a three-proton singlet in the region 3.76-3.92 ppm.
3
*
3J = 7.0-7.2 Hz.
In contrast to the 3-(2-benzazolyl)chromones, the preparation of the aminomethyl derivatives of
3-(2-benzazolyl)coumarins needed more prolonged refluxing of the reaction mixture. Hence the reaction with
bis(dimethylamino/diethylamino)methane was completed in 4-5 h and in the case of the reaction with
4,4'-methylenebismorpholine, 1,1'-methylenebispiperidine, or -bis(4-methylpiperazinyl)methane needed up to
12 h.
1
In contrast to the starting compounds 1e-3e, the H NMR spectra of the Mannich bases 7-12 did not
show the signals for the 8-H of the coumarin ring and, in their place, showed the signals for the protons of the
aminoalkyl substituents. By analogy with 3-(2-benzazolyl)chromones [23], only the monoaminomethyl
derivatives at position 8 of the coumarin ring were obtained and aminomethylation of the benzimidazole NH
group did not occur.
1034

By contrast with the starting materials 1-3, the aminomethylated derivatives of the
3-(2-benzazolyl)coumarins 7-12 are high melting, crystalline materials which are readily soluble in organic
solvents. They are also soluble in dilute mineral acids and some in water. Solutions of the compounds prepared
fluoresce when excited by visible light.
Hence condensation of salicylaldehydes with 2-benzazolylacetonitriles can be used to prepare
3-benzazolylcoumarins. We have shown that secondary amine aminals are efficient reagents for the selective
aminomethylation of coumarins which contain azole substituents.
EXPERIMENTAL
Monitoring of the reaction course and the purity of the compounds prepared was carried out by TLC on
Silufol UV-254 plates. A mixture of chloroform-methanol (9: 1, 95: 5) or ethyl acetate were used as eluent.
1H NMR spectra were measured on Bruker WP 100SY and Varian VXR 300 instruments at working frequencies
of 100 and 300 MHz respectively for solutions in DMSO-d6 (acetone-d6 for compound 5a) and using TMS as
1
internal standard. Parameters for the synthesized compounds are given in Table 1 and H NMR spectra in
Tables 2 and 3.
3-Hetaryl-7-hydroxycoumarins 1a-f to 3a-f. The corresponding substituted 2-hydroxybenzaldehyde
(0.1 mol) and 2-heterylacetonitrile (0.1 mol) were dissolved in the minimum volume of ethanol or 2-propanol at
40-50 C. Piperidine (3-5 drops) was added to the solution and the reaction mixture was held for one day at room
°
temperature. After filtration, the precipitated 2-iminocoumarin was washed with alcohol and refluxed for 2-3 h
in water (500 ml) containing conc. H2SO4 (5-10 ml) in order to hydrolyze the 2-iminocoumarin. The precipitate
formed was filtered off, dried, and recrystallized from DMF or from a mixture of DMF and 2-propanol.
1
3-(2-Benzimidazolyl)-8-methoxycoumarin (1f). H NMR spectrum, , ppm: 9.04 (1H, s, 4-H);
δ
7.17-7.77 (7H, m, 3H coumarin (coum) residue and 4H benzimidazole (bzi) residue); 3.91 (3H, s, OCH3).
1
3-(1-Methylbenzimidazol-2-yl)-8-methoxycoumarin (2f). H NMR spectrum, , ppm: 8.75 (1H, s,
δ
4-H); 7.42-7.90 (7H, m, 3H coum and 4H bzi); 3.98 (6H, s, OCH3 and NCH3).
1
3-(2-Benzothiazolyl)-8-methoxycoumarin (3f). H NMR spectrum, , ppm: 9.15 (1H, s, 4-H);
δ
8.00-8.22 (2H, m, 5- and 8-H benzothiazole (bzt)); 7.32-7.65 (5H, m, 5-, 6-, 7-H coum and 6-, 7-H bzt); 3.94
(3H, s, OCH3).
7-Acyloxy-3-(2-benzazolyl)coumarins (4a, 5a-c, 6a-c). The appropriate acid anhydride or acid
chloride (10 mmol) was added to a solution of the corresponding coumarin 1e-3e (5 mmol) and the mixture was
held for one day at room temperature. The precipitated products 4a, 5a-c, 6a-c were filtered off, washed with
2-propanol, dried, and crystallized from DMF.
1
7-Acetoxy-3-(2-benzimidazolyl)coumarin (4a). H NMR spectrum, , ppm, J (Hz): 9.08 (1H, s, 4-H);
δ
8.05 (1H, d, 3J = 8.8, 5-H); 7.17-7.72 (6H, m, 4H bzi and 6-, 8-H coum); 2.35 (3H, s, 7-OCOCH3).
1
7-Acetoxy-3-(1-methylbenzimidazol-2-yl)coumarin (5a). H NMR spectrum, , ppm: 8.44 (1H, s,
δ
4-H); 7.17-8.00 (7H, m, 3H coum and 4H bzi); 3.87 (3H, s, NCH3); 2.35 (3H, s, 7-OCOCH3).
1
3-(1-Methylbenzimidazol-2-yl)-7-furoyloxycoumarin (5b). H NMR spectrum, , ppm, J (Hz): 8.62
δ
3
(1H, s, 4-H); 8.16 (1H, m, 5-HR); 8.00 (1H, d, J = 8.8, 5-H); 7.20-7.75 (7H, m, 2H coum, 4H bzi, and 3-HR);
6.86 (1H, m, 4-HR); 3.81 (3H, s, NCH3).
1
3-(1-Methylbenzimidazol-2-yl)-7-(4-methoxybenzoyl)oxycoumarin (5c). H NMR spectrum, , ppm,
δ
J (Hz); 8.60 (1H, s, 4-H); 8.0 (1H, d, 3J = 9.0, 5-H); 7.20-7.60 (6H, m, 2H coum and 4H bzi); 7.16 and 8.15 (2H,
2H, two d, 3J = 8.4, HR); 3.89 (3H, s, OCH3); 3.78 (3H, s, NCH3).
1
7-Acetoxy-3-(2-benzothiazolyl)coumarin (6a). H NMR spectrum, , ppm, J (Hz): 9.16 (1H, s, 4-H);
δ
8.07 (1H, d, 3J = 9.0, 5-H); 7.18-8.20 (6H, m, 2H coum, and 4H bzt); 2.33 (3H, s, 7-OCOCH3).
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1
3-(2-Benzothiazolyl)-7-(2-furoyloxy)coumarin (6b). H NMR spectrum, , ppm: 9.26 (1H, s, 4-H);
δ
8.00-8.23 and 7.35-7.70 (4H and 5H, two m, 3H coum, 4H bzt, and 2HR); 6.85 (1H, m, 4-HR).
1
3-(2-Benzothiazolyl)-7-(4-methoxybenzoyl)oxycoumarin (6c). H NMR spectrum, , ppm, J (Hz):
δ
9.23 (1H, s, 4-H); 8.00-8.20 and 7.30-7.65 (5H and 4H, two m, 3H coum, 4H bzt, and 2HR); 7.13 (2H, d,
3J = 8.4, HR); 3.87 (3H, s, OCH3).
3-(2-Benzothiazolyl)-7-mesyloxycoumarins 5d, 6d were prepared similarly to 4a, 5a-c, and 6a-c from
the coumarin 2e, 3e (5 mmol) and methanesulfonyl chloride (0.8 ml, 10 mmol). They were crystallized from a
mixture of DMF and 2-propanol.
1
3-(1-Methylbenzimidazol-2-yl)-7-methylsulfonyloxycoumarin (5d). H NMR spectrum, , ppm,
J (Hz); 8.61 (1H, s, 4-H); 8.03 (1H, d, J = 8.7, 5-H); 7.25-7.80 (6H, m, 2H coum and 4H bzi); 3.79 (3H, s,
δ
3
NCH3); 3.52 (3H, s, 7-OSO2CH3).
1
3-(2-Benzothiazolyl)-7-methylsulfonyloxycoumarin (6d). H NMR spectrum, , ppm, J (Hz): 9.22
(1H, s, 4-H); 8.18 (1H, d, J = 9.0, 5-H); 8.00-8.15 and 7.40-7.65 (4H and 2H, two m, 2H coum and 4H bzt);
δ
3
3.53 (3H, s, 7-OSO2CH3).
7-Alkoxy-3-(2-benzazolyl)coumarins (5e, 6e,f). A mixture of coumarin 2e or 3e (5 mmol), freshly
ignited potassium carbonate (2.5 g, 18 mmol), and dimethylsulfate (0.7 ml, 7 mmol) or ethyl bromoacetate
(0.75 ml, 6.7 mmol) in acetone (30 ml) was refluxed with stirring for 8-10 h. The precipitate was filtered off,
washed with acetone poured into water (300 ml), and neutralized with hydrochloric acid. The precipitated
product was filtered off and crystallized from dimethylformamide.
3-(2-Benzothiazolyl)-2-oxo-2H-chromen-7-yloxyacetic Acid (6g). A solution of the ethyl ester 6f
(1.9 g, 5 mmol) in acetic acid (20 ml) and sulfuric acid (1 ml) was refluxed for 4-5 h. The solution was poured
onto ice and the precipitate was filtered off and crystallized from dimethylformamide.
Aminomethylation of the Coumarins 1e-3e A mixture of the coumarin (5 mmol) and
bis(dimethylamino)methane, bis(diethylamino)methane, bis(morpholino)methane, bis(piperidino)methane, or
bis(4-methylpiperazinyl)methane (6 mmol) in absolute dioxane (25 ml) was refluxed until a clear solution was
obtained. The reaction mixture was cooled and the precipitated crystals were filtered off and recrystallized from
dioxane to give the compounds 7a-b to 9a-b and 10a-c to 12a-c. The diethylaminomethyl derivatives 7-9 were
obtained after evaporation of the reaction mixture and crystallization of the residue from toluene.
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