3-Acetyl/Formyl 4-hydroxy-2
H
(1)-benzopyran-2-one on treatment with malonitrile and ethyl cyanoacetate yielded 1,1-dicyano-2-[4
/
-hydroxy-2
/
H
(1)-benzopyran-2
/
-one-3
/
-yl] ethene/propene 2a-h and ethyl-2-cyano-3-[4
/
-hydroxy-2
/
H (1)-benzopyran-2
/
-one-3
/
-yl] propenoate/butenoate 3a-h respectively. The 1,3 dipolar reaction of 2a-h with NaN
3
gave the tetrazole derivative 4a-h. 3a-h on cyclization with PPA gave 3-cyano-2
H
,5
H
-pyrano [3, 2-
c
] benzopyran-2,5-diones 5a-h which on 1,3 dipolar reaction with NaN
3
to gave 3-(1
/
H
-tetrazol-5
/
-yl)-2
H
,5
H
-pyrano[3, 2-
c
] benzopyran-2,5-diones 6a-h. The structures of the compounds have been established on the basis of the spectral and analytical data. All the compounds were screened for their antimicrobial activities and have been found to exhibited significant antibacterial activities. Compounds 2h and 4h showed the activity 50μg/mL.
INTRODUCTION
Benzopyran-2-ones and pyranobenzopyrones are well known for their biological activities.
1
-
3
Tetrazoles and their derivatives are reputed CNS drugs and having wide application as sedatives
4
and antihypertensive drugs. They are also known for antiallergic,
4
antimicrobial,
5
antilipemic,
6
,
7
carboxylic acid isosteres,
8
anticholinergic, antiimflammatory,
9
hormonal
10
and diuretics
11
activity. They are used as herbicides
12
and radio protective agents.
10
By observing these biological properties, it was thought of synthesizing tetrazole moiety, which is either attached to coumarin or pyranobenzopyran moiety, which may have the above biological activity. All the synthesized compounds were screened for their antibacterial activity.
RESULTS AND DISCUSSION
3-Acetyl-4-hydroxy-2
H
(1)-benzopyran-2-one
13
1a-d
and 3-formyl-4-hydroxy-2
H
(1)-benzopyran-2-one
14
1e-h
were treated with compounds having active methylene group such as malonitrile and ethyl cyanoacetate in presence of piperidine to undergo Knoevenegal condensation to yield 1,1-dicyano-2-[4
/
-hydroxy-2
/
H
(1)-benzopyran-2
/
-one-3
/
-yl]ethene/propene
2a-h
and ethyl-2-cyano-3-[4
/
-hydroxy-2
/
H
(1)-benzopyran-2
/
-one-3
/
-yl]propenoate / butenoate
3a-h
.
2a-h
further undergoes 1,3 dipolar reaction with NaN
3
to give 1,1-di (1
H
tetrazol-5-yl)-2-[4
/
-hydroxy-2
/
H
(1)-benzopyran-2
/
-one-3
/
-yl]-ethene/propene
4a-h
.
3a-h
on cyclization with PPA gave 3-cyano-2
H
,5
H
-pyrano[3,2-
c
]benzopyran-2,5-dione
5a-d
and 3-cyano-4-methyl-2
H
,5
H
-pyrano [3,2-
c
]benzopyran-2,5-dione
5e-h
. 1,3 dipolar reaction of
5a-h
with NaN
3
gave 3-(1
/
H
-tetrazol-5
/
-yl)-2
H
, 5
H
-pyrano[3,2-
c
]benzopyran-2,5-dione
6a-d
and 4-methyl-3-(1
/
H
-tetrazol-5
/
-yl)-2
H
, 5
H
-pyrano [3,2-
c
]benzopyran-2,5-dione
6e-h
. The structures of the compounds
2a-h
to
6a-h
were confirmed on the basis of spectral and analytical data. All the above compounds were screened for their antimicrobial activities.
The minimum inhibition concentration (MIC) was determined using Tube Dilution method according to standard procedure.
15
All the compounds were screened in vitro for their antimicrobial activity against variety of bacterial strains such as
Staphylococcus aureus
,
Salmonella para-typhi
and
Escherichia coli
(
1
). The standard drugs used for comparison were ciprofloxacin (MIC 5 μg/mL), cloxacillin (MIC 10 μg/mL) and gentamycin (MIC 5 μg/mL).
Antimicrobial activity data (MIC μg/mL) of compounds2-6.
250 μg/mL= +, 200 μg/mL= ++, 150 μg/mL= +++, 100 μg/mL= ++++, 50 μg/mL= +++++, Not active up to 250 μg/mL= - Standard drugs were Ciprofloxacin (MIC 5 μg/mL), Cloxacillin (MIC 10 μg/mL) and Gentamycin (MIC 5 μg/mL)
CONCLUSION
The antibacterial activity of the compounds 2-6(a-h) was compared and it was found that amongst them compound 2h and 4h showed significant activity against
S.aureus
,
S.typhi
and
E.coli
. While compounds 2b, 2d, 3h, 4d, 5d, 5h and 6h showed average activity. Compounds 2h and 4h, which lack the pyranonebenzopyranone fused ring system and which have two methyl substituents, out of which one is at the 8
th
position of the benzopyrano ring are predicted to have significantly higher activity than the rest of the compounds.
EXPERIMENTAL
Melting points were taken in open capillaries and were uncorrected. IR spectra (ν
max
in cm
-1
) were recorded on Perkin Elmer FTIR and NMR (
1
H and
13
C) was recorded on Bruker AMX 300 MHz using TMS as standard. Mass spectra were recorded on Shimadzu GC-MS. The homogeneity of the compounds was determined on the silica gel plates. The spots were developed in the iodine chamber. All the compounds gave satisfactory elemental analysis.
- General Method for the synthesis of 1,1-Dicyano-2-[4/-hydroxy-2/H(1) benzopyran-2/-one-3/-yl]ethene/propene 2a-h
A mixture of 3-acetyl/formyl-4-hydroxy-2
H
(1)-benzopyran-2-one
1a-h
(0.01 mol) and malononitrile (0.01 mol) in alcohol and piperidine (0.8 ml) was stirred for 4 hr at room temperature. The reaction was monitored on TLC. It was then decomposed in crushed ice and neutralized with dilute HCl. The solid obtained was filtered, washed and recrystallized from methanol to give dicyano derivatives
2a-h
.
2a:
mp: 198 ℃, yield: 67%.
IR (cm
-1
): 3412(OH), 2245(CN), 1726(C=O), 1620, 1441, 1282, 1138, 784 cm
-1
.
A.E.: Calcd (Found): C, 65.55(65.42); H, 2.52(2.30); N, 11.77(11.56)
2b:
mp: 154℃, yield: 65%.
IR (cm
-1
): 3362(OH), 2204(CN), 1735(C=O), 1618, 1424, 1278, 1147, 776 cm
-1
.
A.E.: Calcd (Found): C, 66.66(66.54); H, 3.17(3.02); N, 11.11(11.13).
2c:
mp: 178℃, yield: 72%.
IR (cm
-1
): 3402(OH), 2205(CN), 1729(C=O), 1620, 1441, 1282, 1138, 784 cm
-1
.
1
H NMR DMSO-d
6
(δ-ppm): 2.39 (s, 3H, CH3), 6.50 (s, 1H, CH=C (CN)
2
), 6.94 (d, 1H, C
6
-H,
J
=7.5
H
z), 7.05 (d, 1H, C
5
-H,
J
=7.5Hz), 7.50 (s, 1H, C
8
-H), 9.10 (s, 1H, OH, D
2
O exchanged).
13
C NMR DMSO-d
6
(δ-ppm): 20.1 (CH3, at C7
/
), 100.0 (C-3
/
), 132.6 (C2), 118.2 (C10
/
), 114.9 (CN), 119.8 (C8
/
), 120.9 (C5
/
), 126.5 (C6
/
), 128.6 (C7
/
), 152.5 (C1
C
(CN)
2
), 156.0 (C9
/
), 163.5 (C4
/
),165.0 (C2
/
).
A.E.: Calcd (Found): C, 66.66(66.62); H, 3.17(3.19); N, 11.11(11.07).
2d:
mp: 168 ℃, yield: 71%.
IR (cm
-1
): 3332(OH), 2212(CN), 1732(C=O), 1621, 1443, 1279, 1143, 782 cm
-1
.
A.E.: Calcd (Found): C, 66.66(66.75); H, 3.17(3.13); N, 11.11(11.10).
2e:
mp: 203 ℃, yield: 75%.
IR (cm
-1
): 3354(OH), 2210(CN), 1707(C=O), 1607, 1445, 1253, 1178, 824 cm
-1
.
A.E.: Calcd (Found): C, 66.66(66.50); H, 3.17(3.00); N, 11.11(11.09).
2f:
mp: 160 ℃, yield: 59%.
IR (cm
-1
): 3357(OH), 2199(CN), 1735(C=O), 1647, 1478, 1281, 1198, 770 cm
-1
.
A.E.: Calcd (Found): C, 67.66(67.45); H, 3.75(3.90); N, 10.52(10.68).
2g:
mp: 224℃, yield: 67%
IR (cm
-1
): 3356(OH), 2202(CN), 1722(C=O), 1618, 1424, 1263, 818 cm
-1
.
A.E.: Calcd (Found): C, 67.66(67.47); H, 3.75(3.88); N, 10.52(10.62).
2h:
mp: > 300 ℃, yield: 66%.
IR (cm
-1
): 3356(OH), 2202(CN), 1722(＞C=O), 1618, 1424, 1263, 1040, 818, 660.
1
H NMR DMSO-d
6
(δ-ppm): 2.36(s, 3H, CH
3
), 2.64(s, 3H, CH
3
), 7.35(t, 1H, C
6
-H,
J
=8.5 Hz), 7.50(d, 1H, C
7
-H,
J
=8.5 Hz), 7.66(d, 1H, C
5
-H,
J
=8.5 Hz), 9.70(s, 1H, OH, D
2
O exchanged).
13
C NMR DMSO-d
6
(δ-ppm): 17.6(CH
3
, at C
8
/
), 21.8 (C
3
), 100(C-
3
/
), 104.5(C
2
), 112.7(C
10
/
), 116.6(CN), 118.8(C
8
/
), 125.5(C
5
/
), 128.5(C
6
/
), 133.3(C
7
/
), 135.0(C
2
), 139.1(C
1
,
C
(CN)
2
), 153.4(C
9
/
), 161.8(C
4
/
), 165.0(C
2
/
).
A.E.: Calcd (Found): C, 67.66(67.47); H, 3.75(3.65); N, 10.52(10.59).
- General Method for the synthesis of 1,1-Di (1H tetrazol-5-yl) 2-[4/-hydroxy-2/H (1)-benzopyran-2/-one 3/-yl] ethene/propene 4a-h
Dicyano compounds 2 (0.01 mol), NH
4
CI (0.02 mol) and NaN
3
(0.02 mol) in DMF were refluxed at 130 ℃ for 19 hr. The cooled reaction mixture was then poured into crushed ice and acidified with HCl to pH 2. The suspension was kept at 4 ℃ for 12 h and was filtered. The residue was washed, dried and recrystallized from ethanol to gave ditetrazoles
4a-h
.
4a:
mp: 225℃, yield: 47%.
IR (cm
-1
): 3423(OH), 1727(C=O), 1625, 1447, 1277, 1156, 776 cm
-1
.
A.E.: Calcd (Found): C, 48.15(48.02); H, 2.47(2.39); N, 34.57(34.49).
4b:
mp: 213℃, yield: 64%.
IR (cm
-1
): 3354(OH), 1733(C=O), 1633, 1445, 1245, 1146, 875 cm
-1
.
A.E.: Calcd (Found): C, 49.70(49.60); H, 2.95(2.82); N, 33.14(33.06).
4c:
mp: ＞300 ℃, yield: 62%.
IR (cm
-1
): 3410(OH), 1714(＞C=O), 1619, 1448, 1259, 1050, 870, 789 cm
-1
.
1
H NMR DMSO-d
6
(δ-ppm): 2.30 (s,3H,CH3), 6.40 (s,1H,CH=C(CN)2), 6.98 (d, 1H, C6/-H,
J
=7 Hz), 7.09 (d, 1H, C5/-H,
J
=7 Hz), 7.29 (s, 1H, C8/-H), 9.15 (s,2H,NH), 10.30 (s,1H,OH, D
2
O exchangeable).
13
C NMR DMSOd
6
(δ-ppm): 20.1(CH
3
, at C
7
/
), 100.0(C
3
/
), 102.0(C
2
), 112.4(C
10
/
), 118.2(C
8
/
), 120.9(C
5
/
), 126.5(C
6
/
), 132.6(C
7
/
), 140.9(C
1
), 152.5(C
9
/
), 163.5(C
4
/
), 165.0(C
2
/
), 156.0(N=C-N).
MS m/z (%): 338 (M+) (71), 299(56), 280(9), 264(13), 249(9), 229(6), 200(6) 178(6), 149(16), 137(84), 121(31), 105(47), 91(62), 77(100), 51(53) etc.
A.E.: Calcd (Found): C, 49.70(49.73); H, 2.95(2.78); N, 33.14(33.17).
4d:
mp: 168 ℃, yield: 54%.
IR (cm
-1
): 3342(OH), 1724(C=O), 1643, 1456, 1288, 1134, 824.
A.E.: Calcd (Found): C, 49.70(49.68); H, 2.95(2.80); N, 33.14(33.12).
4e:
mp: 230 ℃, yield: 65%.
IR (cm
-1
): 3442(OH), 1706(C=O), 1614, 1430, 1210, 1040, 825.
A.E.: Calcd (Found): C, 49.70(49.77); H, 2.95(3.02); N, 33.14(33.19).
4f:
mp: >300 ℃, yield: 57%.
IR (cm
-1
): 3430(OH), 1710(C=O), 1609, 1442, 1207, 1064, 819.
A.E.: Calcd (Found): C, 51.11(51.07); H, 3.40(3.45); N, 31.81(31.92).
4g:
mp: 231 ℃, yield: 49%.
IR (cm
-1
): 3445(OH), 1720(C=O), 1620, 1450, 1370, 1050, 820.
A.E.: Calcd (Found): C, 51.11(51.15); H, 3.40(3.37); N, 31.81(31.90).
4h:
mp: ＞300 ℃, yield: 55%.
IR (cm
-1
): 3439(OH), 1726(C=O), 1619, 1428, 1376, 1200, 1058, 820 cm
-1
.
1
H NMR DMSO-d
6
(δ-ppm): 2.30, 2.62(s, 6H, 2CH
3
), 7.28(t, 1H, C
6
/
-H,
J
= 8.0 Hz), 7.49(d, 1H, C
7
/
-H,
J
=8Hz), 7.65(d, 1H, C
5
/
-H,
J
=8Hz), 9.15(s, 2H, NH) and 10.15(s, 1H, OH, D
2
O exchangeable).
13
C NMR DMSO-d
6
(δ-ppm): 17.6(CH
3
, at C
8
/
), 20(CH
3
, C
3
), 100.5(C
3
/), 102.2(C
2
), 112.5(C
10
/
), 118.2(C
8
/
), 123.3(C
5
/
), 125.6(C
6
/
), 133.6(C
7
/
), 150.8(C
1
), 151.8(C
9
/
), 161.8(C
4
/
), 165.9(C
2
/
), 170.0(N=C-N).
MS m/z(%): 352 (M
+
)(71),322(56), 299(9), 283(13), 264(9), 245(6), 229(6), 214(6), 204(16), 184(84), 176(31), 167(47), 150(62), 145(22), 137(56), 121(31), 108(56), 95(31), 91(40), 77(100), 69(43), 56(56), 41(53).
A.E.: Calcd (Found): C, 51.11(51.18); H, 3.40(3.48); N, 31.81(31.85).
- General Method for the synthesis of Ethyl-2-cyano-3-[4/-hydroxy-2/H(1)-benzopyran-2/-one-3/-yl] propenoate/ butenoate 3a-h
A mixture of 3-acetyl/formyl-4-hydroxy-2
H
(1)-benzopyran-2-one
1a-h
(0.01mol) and ethyl cyanoacetate (0.01 mol) in alcohol in presence of piperidine (1 ml) was refluxed for 12 hr. on water-bath. The reaction was monitored on TLC. After the completion of reaction it was decomposed in crushed ice, neutralized with dilute HCl. The solid obtained was filtered, washed and recrystallised from ethanol to gave cyano esters
3a-h
.
3a:
mp: 164℃, yield: 65%.
IR (cm
-1
): 3415(OH), 2243(CN), 1725(C=O), 1621, 1443, 1283, 1134, 785.
A.E.: Calcd (Found): C, 63.16(63.10); H, 3.86(3.79); N, 4.91(4.89).
3b:
mp: 159 ℃, yield: 62%
IR (cm
-1
): 3342(OH), 2214(CN), 1737(C=O), 1614, 1426, 1274, 1143, 768.
A.E.: Calcd (Found): C, 64.21(64.11); H, 4.35(4.14); N, 4.68(4.72).
3c:
mp: 280 ℃, yield: 72%.
IR (cm
-1
): 3401(OH), 2204(CN), 1731(＞C=O), 1670(＞C=O), 1600, 1442, 1393, 1281, 1186, 1138, 790.
1
H NMR DMSO-d
6
(δ-ppm): 1.30 (t, 3H, CH3), 2.40(s, 3H, CH3), 4.34(q, 2H, CH2), 6.45(s, 1H, C2-H), 7.20(d, 1H, C6/H,
J
=7.5 Hz), 7.30(d, 1H, C5/-H,
J
=7.5 Hz), 7.50 (s,1H, C8/H), 10.90 (s,1H, OH, D
2
O exchanged).
13
C NMR DMSO-d
6
(δ-ppm): 15.0 (
C
H
3
CH
2
), 20.0 (CH
3
), 56.0 (OCH
2
), 100.6 (C
3
/
), 132.6 (C
3
), 118.2 (C
10
/
), 114.9 (CN), 119.8 (C
8
/
), 120.9 (C
5
/
), 126.5 (C
6
/
), 128.6 (C
7
/
), 154.3 (C
9
/
), 151.2 (C
2
), 161.8 (C
4
/
), 163.5 (C
2
/), 166.9 (C
1
,
C
OO).
A.E.: Calcd (Found): C, 64.21(64.18); H, 4.35(4.26); N, 4.68(4.59).
3d:
mp: 163 ℃, yield: 68%.
IR (cm
-1
): 3341(OH), 2219(CN), 1723(C=O), 1642, 1446, 1283, 1149, 781 cm
-1
.
A.E.: Calcd (Found): C, 64.21(64.24); H, 4.35(4.31); N, 4.68(4.63).
3e:
mp: 140 ℃, yield: 75%.
IR (cm
-1
): 3423(OH), 2199(CN), 1705(C=O), 1619, 1461, 1258, 789.
A.E.: Calcd (Found): C, 64.21(64.48); H, 4.35(4.10); N, 4.68(4.50).
3f:
mp: 118℃, yield: 59%.
IR (cm
-1
): 3400(OH), 2210(CN), 1710(C=O), 1644, 1461, 1254, 1179, 759.
A.E.: Calcd (Found): C, 65.17(65.30); H, 4.79(4.85); N, 4.47(4.55).
3g:
mp: 160 ℃, yield: 67%
IR (cm
-1
): 3414(OH), 2211(CN), 1713(C=O), 1645, 1461, 1254, 827.
A.E.: Calcd (Found): C, 65.17(65.20); H, 4.79(4.75); N, 4.47(4.51).
3h:
mp: 180 ℃, yield: 66%.
IR (cm
-1
): 3337(OH), 2202(CN), 1723(C=O), 1615, 1452, 1290, 1065, 819, 785.
1
H NMR DMSO-d
6
(δ-ppm): 1.38 (t, 3H, CH
2
C
H
3
), 2.10(s, 3H, CH
3
), 2.50(s, 3H, CH
3
), 4.39(q, 2H, CH
2
), 7.17(t, 1H, C
6
/
-H,
J
= 8.0 Hz), 7.39(d, 1H, C
7
/
-H,
J
=8.0 Hz), 7.58(d, 1H, C
5
/
-H,
J
=8.0 Hz) 10.80(s, 1H, OH, D
2
O exchanged).
13
C NMR DMSO-d
6
(δ-ppm): 17.7(
C
H
3
CH
2
), 18.2 (C
4
, CH
3
), 20.7 (CH
3
at C
8
), 52(OCH
2
), 99.9(C
3
/
), 102.8(C
3
), 113.1(C
10
/
), 115.4(CN), 118.5(C
8
/
), 123.3(C
5
/
), 125.1(C
6
/
), 133.6(C
7
/
, C-CH
3
), 151.8(C
9
/
), 155.3(C
2
), 161.8(C
4
/
), 165.8(C
2
/
), 170.8(C
4
,COO).
Ms m/z (%): 313(M
+
), 266, 240, 236, 214, 204, 190, 184, 175, 167, 161, 150, 137, 121, 108, 95, 77, 56, 42.
A.E.: Calcd (Found): C, 65.17(65.23); H, 4.79(4.70); N, 4.47(4.41).
- General Method for the synthesis of 3-Cyano-2H,5H-pyrano[3,2-c] benzopyran-2,5-dione 5a-d and 4-Methyl-3-cyano-2H,5H-pyrano[3,2-c]benzopyran-2,5-dione 5e-h.
Cyano esters
3a-h
(0.01 mol) was heated with PPA (30 ml) at 130-135℃ for 15 hrs. The reaction was monitored on TLC. After the completion of reaction, the reaction mixture was cooled and decomposed in crushed ice. The solid obtain was filtered, washed with water and recrystallized from ethanol to gave 3-cyano pyrano benzopyrans
5a-h
.
5a:
mp: 222℃, yield: 56%.
IR (cm
-1
): 2233(CN), 1734(C=O), 1628, 1436, 1276, 1142, 781.
A.E.: Calcd (Found): C, 65.27(65.09); H, 2.09(2.00); N, 5.86(5.82).
5b:
mp: 165 ℃, yield: 61%
IR (cm
-1
): 2208(CN), 1723(C=O), 1623, 1446, 1264, 1137, 771.
A.E.: Calcd (Found): C, 66.40(66.22); H, 2.77(2.65); N, 5.53(5.50).
5c:
mp: ＞300 ℃, yield: 69%.
IR (cm
-1
): 2203(CN), 1716(＞C=O), 1647, 1618, 1444, 1258, 1147, 1080, 788.
1
H NMR DMSO-d
6
(δ-ppm): 2.25(s, 3H, CH3), 6.75(s, 1H, C4-H), 6.97(d, 1H, C9-H,
J
=7.5 Hz), 7.10(d, 1H, C10-H,
J
=7.5Hz), 7.31(s, 1H, C7-H).
13
C NMR DMSO-d
6
(δ-ppm): 20.1(CH
3
), 100.0(C
4a
), 115.9(CN), 119.9 (C
7
), 121.0(C
9
), 122.4(C
10
), 128.0(C
10a
), 130.0(C
4
), 134.0(C
8
), 150.9(C
3
), 152.8(C
6a
and C
11
), 161.8(C
5
), 162.4(C
2
).
A.E.: Calcd (Found): C, 66.40(66.35); H, 2.77(2.58); N, 5.53(5.47).
5d:
mp: 174 ℃, yield: 64%.
IR (cm
-1
): 2206(CN), 1732(C=O), 1644, 1452, 1279, 1152, 784.
A.E.: Calcd (Found): C, 66.40(66.47); H, 2.77(2.73); N, 5.53(5.52).
5e:
mp: 248℃, yield: 65%.
IR (cm
-1
): 2200(CN), 1725(C=O), 1605, 1481, 1268, 770.
A.E.: Calcd (Found): C, 66.40(66.25); H, 2.77(2.80); N, 5.53(5.45).
5f:
mp: 145 ℃, yield: 59%.
IR (cm
-1
): 2202(CN), 1723(C=O), 1615, 1452, 1290, 785.
A.E.: Calcd (Found): C, 67.42(67.55); H, 3.39(3.41); N, 5.24(5.58).
5g:
mp: 205 ℃, yield: 62%.
IR (cm
-1
): 2201(CN), 1720(C=O), 1620, 1555, 821.
A.E.: Calcd (Found): C, 67.42(67.48); H, 3.39(3.31); N, 5.24(5.35).
5h:
mp: 210 ℃, yield: 52%.
IR (cm
-1
): 2196(CN), 1733(C=O), 1647, 1547, 1263, 1188, 1088, 1027, 772.
1
H NMR DMSO-d
6
(δ-ppm): 2.35(s, 3H, CH
3
, C
8
), 2.71(s, 3H, CH
3
, C
4
), 7.30(d, 1H, C
8
-H,
J
=8.0 Hz), 7.47(t, 1H, C
9
-H,
J
=8.0 Hz), 7.85(d, 1H, C
10
-H,
J
=8.0 Hz).
13
C NMR DMSO-d
6
(δ-ppm): 15.2(CH
3
, C
4
), 19.9(CH
3
, C
7
), 101.3(C
4
), 107.5(C
3
), 113.1(C
10a
), 115.4(C
4a
), 118.4(CN), 120.8(C
7
), 123.3(C
10
), 125.1(C
9
), 133.6(C
8
), 151.8(C
6a
and C
11
), 165.8(C
2
and C
5
).
MS m/z (%): 267(M
+
), 241, 190, 177, 175, 157, 150, 144, 136, 121, 115, 108, 91, 84, 77, 63, 51, 44.
A.E.: Calcd (Found): C, 67.42(67.51); H, 3.39(3.33); N, 5.24(5.28).
- General Method for the synthesis of 3-(1/H-tetrazol-5/-yl)-2H, 5H-pyrano[3,2-c]benzopyran-2,5-dione 6a-d 4-Methyl-3-(1/H-tetrazol-5/-yl)-2H,5H-pyrano[3,2-c]benzopyran-2,5-dione 6e-h.
A mixture of 3-cyano pyranobenzopyrans 5 (0.01 mol), NH
4
CI (0.01 mol) and NaN
3
(0.01 mol) in DMF were refluxed for 21 hr. The reaction mixture was cooled, poured into crushed ice and acidified with HCl to pH 2. The suspension was kept at 4℃ for 12 h and was filtered; the residue was washed dried and recrystallized from ethanol to gave 3-tetrazole pyrano benzopyrans
6a-h
.
6a:
mp: 217 ℃, yield: 59%.
IR (cm
-1
): 3341, 3215(NH), 1737(C=O), 1653, 1632, 1445, 1269, 1143, 786.
A.E.: Calcd (Found): C, 55.32(55.34); H, 2.13(2.08); N, 19.86(19.80).
6b:
mp: 254℃, yield: 65%
IR (cm
-1
): 3412, 3398(NH), 1726(C=O), 1673, 1618, 1436, 1266, 1141, 770.
A.E.: Calcd (Found): C, 56.76(56.60); H, 2.70(2.67); N, 18.92(18.79).
6c:
mp: 270℃, yield: 69%.
IR (cm
-1
): 3443, 3210(NH), 1720(＞C=O), 1640, 1620, 1516, 1394, 1267, 1174, 1071, 871, 791.
1
H NMR DMSO-d
6
(δ-ppm): 2.30 (s, 3H, CH
3
), 6.70 (s, 1H, C
4
-H), 7.20 (d, 1H, C
9
-H,
J
=8.5 Hz), 7.31 (d, 1H, C
10
-H,
J
=8.5
H
z), 7.49 (s, 1H, C
7
-H), 9.15 (s, 1H, NH, D
2
O exchanged).
13
C NMR DMSO-d
6
(δ-ppm): 20.1 (CH
3
), 101.5 (C
4a
), 119.5 (C
7
), 121.0 (C
9
), 122.0 (C
10
), 127.5 (C
10a
), 129.5 (C
4
), 132.6 (C
8
), 152.2 (C
6a
and C
11
), 155.3 (N-C=N), 159.1 (C
3
), 162.1(C
5
), 164.5 (C
2
).
MS m/z (%): 296(M
+
), 277(25), 227(47), 214(6), 190(9), 175(28), 161(25), 150(100), 143(25), 137(60), 121(75), 105(56), 91(49), 77(97), 44(49).
A.E.: Calcd (Found): C, 56.76(56.80); H, 2.70(2.72); N, 18.92(18.86).
6d:
mp: 264℃, yield: 66%.
IR (cm
-1
): 3345, 3214(NH), 1723(C=O), 1667, 1643, 1451, 1273, 1151, 783.
A.E.: Calcd (Found): C, 56.76(56.71); H, 2.70(2.61); N, 18.92(18.82).
6e:
mp: ＞300 ℃, yield: 68%.
IR (cm
-1
): 3440, 3378(NH), 1726(C=O), 1662, 1619, 1498, 1298, 819.
A.E.: Calcd (Found): C, 56.75(56.68); H, 3.37(3.31); N, 18.92(18.95).
6f:
mp: 207℃, yield: 57%.
IR (cm
-1
): 3440, 3380(NH), 1727(C=O), 1650, 1620, 1499, 1201, 820.
A.E.: Calcd (Found): C, 58.06(57.98); H, 3.22(3.30); N, 18.06(18.09).
6g:
mp: 233 ℃, yield: 72%.
IR (cm
-1
): 3440, 3380, 1727(C=O), 1650, 1620, 1499, 1201, 819.
A.E.: Calcd (Found): C, 58.06(58.10); H, 3.22(3.15); N, 18.06(18.00).
6h:
mp: 267 ℃, yield: 60%.
IR (cm
-1
): 3439, 3500(NH), 1726(C=O), 1663(＞C=N), 1619, 1428, 1376, 1298, 1201, 1058, 820.
1
H NMR DMSO-d
6
(δ-ppm): 2.15(s, 3H, CH
3
, C
8
), 2.61(s, 3H, CH
3
, C
4
), 7.25(t, 1H, C
9
-H,
J
=7.0 Hz), 7.44(d, 1H, C
8
-H,
J
=7.0 Hz), 7.58(d, 1H, C
10
-H,
J
=7.0 Hz), 8.88(s, 1H, NH, D
2
O exchanged).
13
C NMR DMSO-d
6
(δ-ppm): 17.5(CH
3
, C4), 21.2(CH
3
, C
7
), 100.8(C
4
), 110.2(C
3
), 112.0(C
10a
), 117.1(C
4a
), 125.0(C
7
), 126.1(C
10
), 125(C
9
), 135(C
8
), 153.1(C
6a
and C
11
), 158(N-C=N), 167.1(C
2
and C
5
).
MS m/z (%): 310(M
+
) (56), 241(25), 236(47), 229(6), 215(9), 204(16), 184(49), 178(28), 150(100), 145(25), 137(60), 121(75), 108(56), 95(49), 77(97), 42(49), 41(40).
A.E.: Calcd (Found): C, 58.06(58.12); H, 3.22(3.17); N, 18.06(17.98).
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,
Romussi G.
,
Ciarallo G.
,
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1983
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,
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,
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,
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,
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,
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1406 -
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