Reaction of 4-oxochromene-3-carboxaldehydes with primary amides and benzotriazole or 1H-1,2,4-triazole

Article abstract of DOI:10.1135/cccc19970781

N-[(6-substituted-4-oxochromen-3-yl)(1,2,4-triazol-3-yl)methyl]amides 5 and N-[(6-substituted-4-oxochromen-3-yl)(benzotriazol-1-yl)methyl]amides 6 were prepared by the reaction of 6-substituted 4-oxochromene-3-carboxaldehydes 1 with primary amides and 1H-1,2,4-triazole or 1H-benzotriazole. 6-Substituted 3-[hydroxy(1,2,4-triazol-1-yl)methyl]chromen-4-one 2 and 6-substituted 3-[hydroxy-(benzotriazol-1-yl)methyl]chromen-4-one 3 were isolated as stable intermediates of these reactions. Beneficial effect of microwave irradiation on length of reaction time was observed. Some reactions of these derivatives with O, S, and N nucleophiles are described.

Full text of DOI:10.1135/cccc19970781

4-Oxochromene-3-carboxaldehydes
781
REACTION OF 4-OXOCHROMENE-3-CARBOXALDEHYDES WITH
PRIMARY AMIDES AND BENZOTRIAZOLE OR 1H-1,2,4-TRIAZOLE
1
2
3,
Henrieta STANKOVICOVA , Renata GASPAROVA , Margita LACOVA *
4
and Jarmila CHOVANCOVA
Department of Organic Chemistry, Faculty of Natural Science, Comenius University,
842 15 Bratislava, Slovak Republic; e-mail: 1 stankovicova@fns.uniba.sk, 2
gasparova@fns.uniba.sk, 3 lacova@fns.uniba.sk, 4 organika@fns.uniba.sk
Received October 1, 1996
Accepted January 4, 1997
N-[(6-substituted-4-oxochromen-3-yl)(1,2,4-triazol-3-yl)methyl]amides 5 and N-[(6-substituted-4-oxo-
chromen-3-yl)(benzotriazol-1-yl)methyl]amides 6 were prepared by the reaction of 6-substituted
4-oxochromene-3-carboxaldehydes 1 with primary amides and 1H-1,2,4-triazole or 1H-benzotriazole.
6-Substituted 3-[hydroxy(1,2,4-triazol-1-yl)methyl]chromen-4-one 2 and 6-substituted 3-[hydroxy-
(benzotriazol-1-yl)methyl]chromen-4-one 3 were isolated as stable intermediates of these reactions.
Beneficial effect of microwave irradiation on length of reaction time was observed. Some reactions
of these derivatives with O, S, and N nucleophiles are described.
Key words: 4-Oxochromene-3-carboxaldehydes; Microwave irradiation; Enamides.
Chromenone derivatives are important heterocyclic compounds due to their widespread
occurrence in plants and their potential as important pharmaceuticals. The reactivity of
4-oxo-chromene-3-carboxaldehydes has been the focus of much interest as these com-
pounds are useful intermediates in the synthesis of a wide variety of heterocycles; they
undergo both nucleophilic attack at the carbonyl function as well as conjugate addi-
tion1–3. Our recent investigations were devoted to the synthesis of new derivatives of
chromones4–6 and to the study of biological5,6, spectral and theoretical7,8 aspects of re-
actions of 4-oxochromene-3-carboxaldehydes, such as reactions with active methylene
groups of various heterocycles4, with amines5 or hydrazide groups6.
It is known that the amide group is an important constituent of many biologically
important compounds. Therefore, we aimed at searching for a convenient method for
preparation of chromenone derivatives containing various amide moieties. Our interest
was focused to 1H-1,2-4-triazole or 1H-benzotriazole, as potential building blocks of
the target compounds.
* The author to whom correspondence should be addressed.
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

782
Stankovicova, Gasparova, Lacova, Chovancova:
Our investigations led to an extension of the utilization of 4-oxochromene-3-carbox-
aldehydes 1 in reaction with two base components 1H-1,2,4-triazole or 1H-benzotria-
zole to form stable alcohols 2 and 3, and their reaction with amides 4 to form
aminal-type derivatives 5 and 6 (Scheme 1). We found that the reaction can be further
extended to 4-oxo-chromene-3-carboxaldehydes and primary aliphatic, aromatic and
heterocyclic amides.
The advantage of the reactions is that, unlike the starting compounds, the products 5
and 6 are little soluble in hot toluene, precipitating from reaction mixture thus and
indicating the course of reaction. Equivalent amounts of starting compounds, on reflux-
ing in dry toluene for 18–50 h give amides 5 and 6 as solid in the yields 50–90% (Table I).
Using xylene instead of toluene leads to lower yields and difficult isolation of the pro-
ducts.
As microwaves are known to shorten reaction time in various types of reactions4,9,10
,
we have studied the effect of microwave heating on the yields of products 5 and 6. We
found out that the yields under classic conditions and those in the microwave oven
were comparable. The only difference was in shorter reaction times (17–33 min).
The structures of compounds 5 and 6 were established from IR and 1H NMR spectra.
IR spectra revealed the presence of a strong band of a stretching frequency of pyrone
carbonyl at 1 675–1 640 cm–1, of amide 1 640–1 620 cm–1 and a medium band of
1
C=C at 1 620–1 600 cm–1 (Table II). H NMR spectra of compounds 5 and 6 showed
doublets of NH protons at δ 12.9–9.11 and CH protons at δ 8.2–7.99 and a singlet of
H-2 of pyranone ring at δ 8.90–8.70 (Table III).
The assumption that the first step of the studied reaction is the formation of 3-[hy-
droxy(1,2,4-triazol-1-yl)methyl]chromen-4-ones 2 or 3-[hydroxy(benzotriazol-1-yl)-
methyl]chromen-4-ones 3 was confirmed by isolation of derivatives 2 and 3 (Scheme 1).
The products 2a and 3a underwent a 15 h reaction with benzamide in refluxing toluene
to yield compounds 5b or 6d, respectively.
IR spectra of hydroxy derivatives 2a, 2b, 3a, and 3b showed broad absorptions band
1
of bonded OH group at 3 189–3 140 cm–1, while H NMR spectra of these compounds
revealed signals of OH proton at δ 2.30–1.56, which disappeared after treatment with
deuterium oxide (Tables II and III). 1H NMR spectra of the compounds 2 and 3 indicate
the absence of equilibria with the starting materials. Compounds 2 and 3 are stable in
aprotic solutions. No 1H NMR signal of aldehyde proton could be found.
A successful preparation of compounds 2, 3, 5 and 6 requires special attention to
purification of each component of the reaction mixture. In the presence of traces of
water a mixture of undefined products is formed. The products, after drying at room
temperature, could be stored in capped vials for months without any decomposition.
Compounds 5 and 6 readily undergo reactions with nucleophiles under mild condi-
tions. Such reactions make it possible to prepare chromane derivatives of enamide type
7 as stable products in 50–75% yields (Scheme 2, Table I). For the reactions, various
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

4-Oxochromene-3-carboxaldehydes
783
O
O
1
CHO
R
1
dry toluene
reflux
N
N
N
N
∆
∆
N
H
N
H
N
N
O
O
N
N
N
N
1
1
CH
OH
CH
R
R
O
O
OH
2
3
2
2
R CONH
R CONH
∆
∆
2
2
4
4
10
1
1
8
8
5
10
N
O
O
11
12
7
6
7
2
2
N
N
N
9
9
4
4
N
N
1
1
3
3
6
CH
CH
R
11
2
13
R
5
2
O
O
NHCOR
NHCOR
5
6
R1
R2
R1
R2
-
NO2
Cl
H
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
CH3
CH3
CH3
3-pyridyl
3-pyridyl
4-pyridyl
1a
5a
5b
5c
-
Cl
1b
1c
-
H
NO2
H
-
CH3
Br
NO2
Cl
1d
1e
2a
2b
3a
6a
6b
6c
6d
6e
-
CH3
Br
-
-
Cl
-
NO2
Cl
NO2
H
-
3b
4a
4b
4c
4d
6f
6g
6h
6i
-
C6H5
CH3
3-pyridyl
4-pyridyl
Br
-
Cl
-
Cl
-
NO2
Cl
6j
6k
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

784
Stankovicova, Gasparova, Lacova, Chovancova:
TABLE I
Characteristic data of prepared compounds
Calculated/Found
Reflux, h
Formula
M.w.
M.p., °C
Starting
Compound
Yield, % compounds MW, min
% C
% H % N % Cla
2a
2b
3a
3b
5a
5b
5c
6a
6b
6c
6d
6e
6f
C12H8N4O5
288.2
80–84
89
1a
8
–
50.01 2.80 19.44
49.85 2.80 19.29
–
–
C
C
C
C
C
C
C
C
C
C
C
C
C
C
12H8ClN3O3
277.7
104–105
85
1b
8
–
51.91 2.90 15.13 12.77
51.75 2.75 15.12 12.77
16H10N4O5
338.3
223–225
90
1a
8
–
56.81 2.98 16.56
56.87 2.87 16.45
–
–
16H10ClN3O3
327.7
111–114
85
1b
8
–
58.64 3.08 12.82 10.65
58.60 3.06 12.74 10.65
19H14N4O3
346.4
158–160
80
1c, 4a
1b, 4a
1a, 4a
1c, 4a
1d, 4a
1e, 4a
1b, 4a
1a, 4a
1c, 4b
1e, 4b
1b, 4b
24
–
65.89 4.07 16.18
65.85 4.06 16.08
–
–
19H13ClN4O3
380.8
196–199
85
24
–
59.93 3.44 14.71 9.31
59.91 3.40 14.69 9.28
19H13N5O5
391.3
102–105
89
20
10
58.31 3.35 17.90
58.16 3.29 17.75
–
–
23H16N4O3
396.4
212–214
70
27
–
69.69 4.14 14.13
69.46 4.07 14.12
–
–
24H18N4O3
410.4
190–192
88
27
33
70.23 4.42 13.65
69.85 4.38 13.42
–
–
23H15BrN4O3
475.3
229–231
85
27
–
58.12 3.18 11.78 16.81
58.11 3.16 11.76 16.65
23H15ClN4O3
430.8
222–225
90
27
20
64.12 3.51 13.00
64.05 3.50 12.89
8.23
8.21
23H15N5O5
441.4
225–227
84
27
27
62.58 3.43 15.87
62.49 3.39 15.86
–
–
18H14N4O3
322.3
183–186
70
50
–
63.35 4.38 17.38
63.08 4.18 17.17
–
–
6g
6h
18H13BrN4O3
401.2
228–231
78
50
20
50.89 3.26 13.96 19.91
50.75 3.12 13.60 19.70
18H13ClN4O3
356.7
224–227
80
50
–
57.23 3.67 15.70
56.97 3.52 15.57
9.94
9.91
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

4-Oxochromene-3-carboxaldehydes
785
TABLE I
(Continued)
Calculated/Found
% H % N % Cla
Formula
M.w.
M.p., °C
Starting
Reflux, h
Compound
Yield, % compounds MW, min
% C
6i
C22H14ClN5O3
431.6
240–242
85
1b, 4c
1a, 4c
1b, 4d
6d
18
11
61.19 3.27 16.22 8.02
60.95 3.15 16.17 8.01
6j
C22H14N6O5
442.4
219–222
79
18
–
59.73 3.19 19.00
59.72 3.18 18.85
–
–
6k
7a
7b
7cb
7db
7e
7f
C22H14ClN5O3
431.6
215–218
50
48
–
61.19 3.27 16.22 8.02
60.84 3.26 16.05 8.02
C
19H16ClNO4
357.7
186–190
70
3
–
63.78 4.51
63.65 4.24
3.96
3.71
9.91
9.86
C19H16N2O6
368.4
225–227
68
6e
3
–
61.96 4.38
61.79 4.35
7.61
7.58
–
–
C24H18ClNO3S
435.9
169–172
55
6d
10
–
66.13 4.16
65.97 4.09
3.21
3.16
8.13
7.99
C23H16ClNO3S
421.8
145–147
50
6a
10
–
65.48 3.82
65.35 3.76
3.32
3.27
8.40
8.35
C20H17ClN2O3
368.8
175–177
64
5b
4
–
65.13 4.65
65.09 4.63
7.60
7.59
9.61
9.60
C20H20ClN3O3
385.9
162–164
60
6k
4
–
62.26 5.22 10.89
62.25 5.18 10.78
9.19
9.15
7g
7h
C25H29ClN2O3
441.0
214–217
67
6d
4
–
68.09 6.63
68.01 6.61
6.35
6.35
8.04
8.02
C21H20ClN3O3
397.9
187–190
58
6k
4
–
63.40 5.07 10.56
63.38 5.01 10.54
8.91
8.86
a % Br for compounds 6c and 6g; b % S: 7c calculated: 7.35, found: 7.26; 7d calculated: 7.60, found:
7.49.
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

786
Stankovicova, Gasparova, Lacova, Chovancova:
O, S, N nucleophiles were used. Formation of enamide derivatives 7 can be explained
by interaction of nucleophile. Nucleophilic attack on the 2-position of the chromenone
ring in compounds 5 and 6 is followed by double bond shift and elimination of 1H-
1,2,4-triazole or 1H-benzotriazole in the final step of the reaction. This reaction step
was proved by isolation of both azoles from NaHCO3 filtrate after acidification.
4
R
X
H
O
O
O
O
4
R XH
3
3
R
R
1
1
CH
NHCOR
CH
R
R
2
2
NHCOR
5, 6
3
5, R = 1,2,4-triazol-1-yl
3
6, R = benzotriazol-1-yl
4
R
O
O
X
1
2
CH
R
NHCOR
7
1
2
4
X
R
R
R
Cl
C H
6
O
O
S
S
C H
2
7a
7b
7c
7d
7e
5
5
5
5
5
5
5
NO
Cl
H
C H
6
C H
2
2
C H
6
CH C H
2 6 5
C H
6
4-ClC H
6 4
Cl
Cl
Cl
Cl
C H
6
NH CH CH CH
2 2
4-pyridyl NH C H
7f
4
9
C H
N
N
(C H )
7g
7h
6
5
4
9 2
4-pyridyl
CH )
2 5
SCHEME 2
IR spectra of compound 7 indicated the presence of CO and NH groups (Table II).
1H NMR revealed signal at δ 5.8–7 ppm thus supporting the presence of H-2 on a
chromanone system and not on a chromenone system (Table III).
EXPERIMENTAL
1
Melting points were determined on a Kofler hot stage and are uncorrected. H NMR spectra (δ, ppm;
J, Hz) were measured on Spectrometer BS-487 (80 MHz, Tesla) in deuteriochloroform or
hexadeuteriodimethyl sulfoxide with tetramethylsilane as internal standard. The reaction course was
monitored by thin-layer chromatography in ethyl acetate–isohexane. The microwave synthetic study
was realized using a DAEWOO microwave oven at 270 W in an Erlenmeyer flask with condenser
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

4-Oxochromene-3-carboxaldehydes
787
according to the described procedure10. The characteristic data of the prepared compounds and the
1
reaction data are given in Table I, the IR spectra in Table II and the H NMR spectra in Table III.
6-Substituted 3-[Hydroxy(1,2,4-triazol-1-yl)methyl]chromen-4-one 2 and 6-Substituted
3-[Hydroxy(benzotriazol-1-yl)methyl]chromen-4-one 3. General Procedure
6-Substituted 4-oxochromene-3-carboxaldehyde 1a–1e (2 mmol) and 1H-1,2,4-triazole or 1H-benzo-
triazole (2 mmol) were refluxed in dry toluene (5 ml) for 8 h. The solid product was filtered off,
stirred with diethyl ether or acetone at room temperature for 1 h and dried.
N-[(6-Substituted-4-oxochromen-3-yl)(1,2,4-triazol-1-yl)methyl]amides 5 and N-[(6-Substituted-4-
oxochromen-3-yl)(benzotriazol-1-yl)methyl]amides 6. General Procedure
Method A. 6-Substituted 4-oxochromene-3-carboxaldehyde 1a–1e (2 mmol), primary amide 4a–4d
(2 mmol) and 1H-1,2,4-triazole or 1H-benzotriazole (2 mmol) in dry toluene (10 ml) were refluxed
for 27–50 h. The solid product was filtered off, stirred first with diethyl ether and then with acetone
TABLE II
~
IR spectra (ν, cm–1) of synthesized compounds measured in paraffinic oil
Com-
pound
~
~
~
~
~
~
~
ν(NH)
ν(OH)
ν(NH)
ν(CO)pyrone ν(CO)amide ν(C=C) δ(ΝΗ) ν(C–O–C)
a
2b
3b
5a
5b
5c
–
3 120–2 995
–
1 655
1 640
1 675
1 640
1 650
1 650
1 650
1 645
1 670
1 645
1 650
1 665
1 648
1 654
1 657
1 650
1 680
–
1 620
1 620
–
–
1 120
1 130
1 140
1 140
1 130
1 150
1 110
1 125
1 150
1 150
1 110
1 170
1 152
1 195
1 095
1 160
1 120
a
–
3 102–2 890
–
–
3 330
3 310
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
3 120–2 990
3 110–2 980
3 110–2 990
3 080–2 900
3 090–2 990
3 090–2 900
3 105–2 920
3 110–2 990
3 110–2 980
3 130–3 020
3 080–2 975
–
1 640
1 635
1 640
1 640
1 638
1 630
1 660
1 630
1 620
1 640
1 638
1 605
1 613
1 625
1 640
1 615 1 520
1 600 1 530
1 620 1 530b
1 600 1 510
1 605 1 510
1 600 1 510
1 620 1 530
1 618 1 540a
1 600 1 515
1 620 1 530a
1 615 1 512
1 590 1 550
1 594 1 525a
1 600 1 510
1 600 1 520
6a
6b
6c
3 400
3 375
3 375
3 400
3 280
3 280
3 210
3 360
–
6d
6e
6g
6j
6k
7ab
7bb
7c
–
–
3 295
3 250
3 090–3 030
3 070–2 990
7h
a
–1
–1 b
~
~
νas(NO2) 1 530–1 520 cm , νs(NO2) 1 355–1 340 cm
;
measured in chloroform.
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

788
Stankovicova, Gasparova, Lacova, Chovancova:
TABLE III
1H NMR spectral data of synthesized compounds
Compound
δ, ppm; J, Hz
2aa
2ba
3aa
1.87 s, 1 H (OH); 6.65 s, 1 H (H-9); 7.51 s, 1 H (H-triazole); 7.59 dd, 1 H, J(7,8) = 9,
J(7,5) = 2.4 (H-7); 7.97 s, 1 H (H-triazole); 8.09 d, 1 H, J(8,7) = 9 (H-8); 8.42 s, 1 H
(H-2); 8.46 d, 1 H, J(5,7) = 2.4 (H-5)
2.30 s, 1 H (OH); 7.20 s, 1 H (H-9); 7.75 d, 1 H, J(8,7) = 5.79 (H-8); 8.06 s, 1 H
(H-triazole); 8.24 s, 1 H (H-triazole); 8.52 s, 1 H (H-2); 8.57 dd, 1 H, J(7,5) = 2.74,
J(7,8) = 5.79 (H-7); 9.04 d, 1 H, J(5,7) = 2.74 (H-5)
1.95 s, 1 H (OH); 7.23 s, 1 H (H-9); 7.34–7.50 m, 4 H (H-10-13); 7.57 d, 1 H,
J(8,7) = 2.44 (H-8); 7.69 dd, 1 H, J(7,8) = 2.44, J(7,5) = 1.83 (H-7); 8.05 d, 1 H,
J(5,7) = 1.83 (H-5); 8.58 s, 1 H (H-2)
3ba
5a
1.56 s, 1 H (OH); 7.30–7.80 m, 5 H (H-9-13); 8.16 s, 1 H (H-2); 8.38–8.68 m, 2 H
(H-7,8); 9.07 d, 1 H, J = 2.44 (H-5)
7.48–7.99 m, 10 H (arom.); 8.10 d, 1 H, J = 7.9 (H-9); 8.60 s, 1 H (H-triazole); 8.81 s,
1 H (H-2); 9.69 d, 1 H, J = 7.9 (NH)
5b
7.20–7.64 m, 5 H (arom.); 7.93 d, 1 H, J = 5.94 (H-8); 7.99 d, 1 H, J = 7.93 (H-9);
7.84–8.05 m, 2 H (arom.); 8.60 d 1 H, J = 5.94 (H-7); 8.64 s, 1 H (H-triazole); 8.80 s,
1 H (H-2); 9.69 d, 1 H J = 7.93 (NH)
5c
7.06–7.67 m, 3 H (arom.); 7.81–8.06 m, 4 H (arom.,H-triazole); 8.11 d, 1 H, J = 8.24
(H-9); 8.57 d, 1 H, J = 2.74 (H-8); 8.70 s, 1 H (H-2); 8.70 s, 1 H (H-2); 8.77 d, 1 H,
J = 2.74 (H-7); 8.84 s, 1 H (H-5); 9.71 d, 1 H, J = 8.24 (NH)
6a
6b
6c
6d
6e
6f
7.44–8.04 m, 13 H (arom.); 8.20 d, 1 H, J = 8.54 (H-9); 8.81 s, 1 H (H-2); 10.11 d,
1 H, J = 8.54 (NH)
2.42 s, 3 H (CH3); 7.42–8.033 m, 12 H (arom.); 8.20 d, 1 H J = 9 (H-9); 8.76 s, 1 H
(H-2); 10.04 d, 1 H, J = 9 (NH)
7.45–8.04 m, 12 H (arom.); 8.18 d, 1 H, J = 8.54 (H-9); 8.84 s, 1 H (H-2); 10.09 d, 1
H, J = 8.54 (NH)
7.42–8.01 m, 12 H (arom.); 8.17 d, 1 H, J = 8.54 (H-9); 8.85 s, 1 H (H-2); 10.09 d, 1
H, J = 8.54 (NH)
7.43–8.06 m, 6 H (arom.); 8.13–8.76 m, 7 H (arom.,H-9); 8.90 s, 1 H (H-2); 10.05 d,
1 H, J = 8.8 (NH)
2.01 s, 3 H (CH3); 7.35–8.13 m, 9 H (arom.,H-9); 8.81 s, 1 H (H-2); 9.72 d, 1 H
J = 9 (NH)
6g
6h
6i
1.97 s, 3 H (CH3); 7.43–8.09 m, 8 H (arom.,H-9); 8.84 s, 1 H (H-2); 9.68 d, 1 H,
J = 9 (NH)
1.98 s, 3 H (CH3); 7.42–8.08 m, 8 H (arom.,H-9); 8.83 s, 1 H (H-2); 9.72 d, 1 H,
J = 9 (NH)
6.99–8.61 m, 11 H (arom.,H-9); 8.73 s, 1 H (H-2); 9.07 s, 1 H (H-2 pyridine); 9.11 d,
1 H, J = 8.4 (NH)
6j
7.4–8.60 m, 10 H (arom.,H-9); 8.71 s, 1 H (H-2); 8.96 s, 1 H (H-5); 9.13 s, 1 H
(H-2 pyridine); 10.29 d, 1 H, J = 8.54 (NH)
6k
7.62 d, 1 H, J = 8.54 (H-9); 7.45–8.83 m, 10 H (arom.,H-2); 10.30–10.50 m, 2 H
(H-pyridine); 12.90 d, 1 H, J = 8.54 (NH)
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

4-Oxochromene-3-carboxaldehydes
789
TABLE III
(Continued)
Compound
δ, ppm; J, Hz
7aa
7ba
7ca
7d
1.20 t, 3 H, J = 7.08 (CH3); 3.74–3.89 q, 2 H (CH2); 5.81 s, 1 H (H-2); 6.93–8.09 m,
9 H (arom.,H-9); 12.61 d, 1 H, J = 11 (NH)
1.22 t, 3 H, J = 7.02 (CH3); 3.78–3.93 q, 2 H (CH2); 5.98 s, 1 H (H-2); 7.11–8.45 m,
8 H (arom.); 8.88 d, 1 H, J = 11.6 (H-9); 12.59 d, 1 H, J = 11.6 (NH)
3.93, 3.99 2 × s, 2 H (CH2); 6.18 s, 0.5 H (H-2); 6.29 s, 0.5 H (H-2); 7.19–8.20 m,
14 H (arom.,H-9); 8.28 d, 1 H, J = 10 (NH)
6.34 s, 0.5 H (H-2); 6.46 s, 0.5 H (H-2); 7.19–7.97 m, 12 H (arom.); 8.21 d, 1 H,
J = 9.76 (H-9); 8.71 d, 1 H, J = 9.76 (NH)
7e
3.89 m, 2 H (CH2); 5.30 d, 2 H, J = 12.5 (CH2=); 5.73–5.93 m, 1 H (CH=); 6.86 s,
0.5 H (H-2); 6.98 s, 0.5 H (H-2); 7.10–8.46 m, 10 H (arom.,H-9,NH); 10.20 br s, 1 H
(NH-amide)
7f
7g
7h
0.83 t, 3 H (CH3); 1.38 m, 5 H (CH2–CH2,NH); 3.21 q, 2 H (CH2); 6.75 s, 0.5 H (H-2);
6.84 s, 0.5 H (H-2); 7.00–7.68 m, 3 H (arom.,H-9); 7.81 d, 2 H, J = 2.7 (H-3 pyridine);
8.65–8.73 m, 3 H (H-3 pyridine,H-5); 9.89 d, 1 H, J = 12.5 (NH-amide)
0.90, 0.97 2 × t, 6 H (CH3,CH3); 1.46 m, 8 H (2 × CH2–CH2); 3.69 2 × q, 4 H
(2 × CH2); 6.8 s, 0.5 H (H-2); 6.9 s, 0.5 (H-2); 7.09–8.16 m, 9 H (arom.,H-9); 8.56 d,
1 H, J = 9 (NH)
1.12 m, 2 H (CH2); 1.74 m, 4 H (2 × CH2); 3.47 q, 4 H (2 × CH2–N); 6.87 s, 0.5 H
(H-2); 6.98 s, 0.5 H (H-2); 7.22–7.51 m, 4 H (arom.,H-9); 8.06 d, 2 H, J = 6.01
(H-3 pyridine); 8.72 d, 2 H, J = 6.01 (H-2 pyridine); 10.08 d, 1 H, J = 7.63 (NH)
a Measured in deuteriochloroform.
at room temperature for 1 h and dried. From the reaction mixture filtrate toluene was removed at
60 °C/4 kPa. The residue was successively treated with diethyl ether and acetone and then filtered
off. Both products were identical.
Method B. 6-Substituted 4-oxochromene-3-carboxaldehyde 1a–1e (2 mmol), primary amide 4a–4d
(2 mmol) and 1H-1,2,4-triazole or 1H-benzotriazole (2 mmol) in dry toluene (10 ml) were irradiated
in a microwave oven for 17–33 min. Toluene was removed and the solid product was washed with
diethyl ether and with acetone and finally dried.
N-[(2,6-Disubstituted-4-oxochroman-3-ylidene)methyl]carboxamides 7. General Procedure
Method A (Preparation of compounds 7a, 7b). Compound 6d or 6e (2 mmol) was refluxed in ethanol
for 3 h. The solid product was filtered off, washed with cold water, dried and crystallized from
ethanol.
Method B. To a hot solution of compound 5 or 6 (2 mmol) in dry dioxane, a dioxane solution of
2 mmol of the corresponding nucleophilic agent phenylmethanethiol, 4-chlorothiophenol, allylamine,
butylamine, dibutylamine or piperidine was added. The reaction mixture was refluxed for 4–10 h.
After distilling off dioxane, cold (5 °C) saturated solution of NaHCO3 (15 ml) was added to the
residue and stirred for 15 min at room temperature. The solid product was filtered off, washed with
water and dried. The filtrate was acidified, precipitated azoles were filtered off and dried.
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

790
Stankovicova, Gasparova, Lacova, Chovancova:
The authors thanks are due to Dr E. Greiplova for elemental analyses, Dr E. Solcaniova for measure-
1
ment of H NMR spectra and Dr A. Perjessy for IR spectral measurements (all members of Faculty of
Natural Science, Comenius University, Bratislava). Financial support for this research by the Slovak
Grant Agency is gratefully acknowledged.
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