Synthesis and reactions of naphtho[1′,2′:4,5]furo[3,2-b] pyridine and naphtho[1′,2′:4,5]furo[3,2-d]pyrimidine derivatives

Article abstract of DOI:10.1002/jccs.200700151

2-Acyl-3-aminonaphtho[2,1-b]furan (1) reacts with activated methylene such as malono nitrile or ethyl cyanoacetate to afford naphtho[1′,2′:4,5] furo[3,2-b]pyridine 2a,b. Chloroacylation of the amino group in compound (1) gave compound 3 which reacts with

Full text of DOI:10.1002/jccs.200700151

Journal of the Chinese Chemical Society, 2007, 54, 1045-1052
1045
Synthesis and Reactions of Naphtho[1¢,2¢:4,5]furo[3,2-b]pyridine and
Naphtho[1¢,2¢:4,5]furo[3,2-d]pyrimidine Derivatives
M. Z. A. Badr, A. M. Kamal El-Dean,* O. S. Moustafa and R. M. Zaki
Chemistry Department, Faculty of Science, Assiut University, Assiut 71516, Egypt
2-Acyl-3-aminonaphtho[2,1-b]furan (1) reacts with activated methylene such as malono nitrile or
ethyl cyanoacetate to afford naphtho[1¢,2¢:4,5]furo[3,2-b]pyridine 2a,b. Chloroacylation of the amino
group in compound (1) gave compound 3 which reacts with different amines to produce compound 4.
Keywords: Synthesis; Reactions; Naphthofuran; Naphthofuropyridines; Naphthofuropyrimidines.
INTRODUCTION
Benzo[b]furan moiety constitutes a major group of
2b. The structure of compound 2b was elucidated using IR
spectra; it gave a characteristic band for NH at 3490 and at
1
2220 cm-1 for CN group and at 1640 cm-1 for -C=O. H
natural biologically active heterocycle compounds,1–5 which
have attracted much attention owing to their wide range of
biological activities, such as acting as antioxidants, anti-
fungal agents, modulators of estrogen receptors, 5-lipoxy-
genase inhibitors, cyclooxygenase-2 inhibitors, and Na+,
K+-ATPase inhibitors.6–11
NMR (DMSO-d6) gave a signals at 2.55 as a singlet for
CH3, 7.7-9.0 for aromatic protons and at 9.25 for -NH
group.
Chloroacylation of (1) using chloroacetyl chloride in
dioxan followed by treating with sodium carbonate solu-
tion afforded 2-acetyl-3-chloroacetylaminonaphtho[2,1-
b]furan (3). The structure of the produced compound was
elucidated on the basis of NMR spectra, which revealed the
disappearance of signals at 6.55 characteristic for -NH2-
and appearance of signals at d 4.5 characteristic for -CH2-
and at 11.9 for -NH-.
RESULTS AND DISCUSSION
When 2-acetyl-3-aminonaphtho[2,1-b]furan (1a)
refluxed with malononitrile in ethanol in the presence of
catalytic drops of piperidine, 2-amino-4-methylnaphtho-
[1¢,2¢:4,5]furo[3,2-b]pyridine-3-carbonitrile 2a was pro-
duced. The reaction proceeded through Knovenagel con-
densation followed by addition of amino group to cyano
group to give compound 2a. The same compound was pre-
pared under another condition by using ammonium acetate/
acetic acid mixture. The confirmation of the produced com-
pound was performed using IR spectra which showed a
band at 3390, 3290 cm-1 characteristic for (NH2), and at
2220 cm-1 (CN) and also revealed the disappearance of the
band characteristic for -C=O in the starting material.
While when compound (1a) was refluxed with ethyl
cyanoacetate in ammonium acetate in acetic acid as a sol-
vent, condensation of the carbonyl group with active meth-
ylene followed by elimination of ethanol to give 3-cyano-
4-methyl-naphtho[1¢,2¢:4,5]furo[3,2-b]pyridin-2(1H)-one
Chloroacetyl derivative 3 underwent nucleophilic
substitution reaction with various primary and secondary
amines in refluxed ethanol to afford N-[2-acetylnaphtho-
[2,1-b]furan-3-yl]-2-alkyaminoacetamide 4. Also when
the chlorine atom in compound 3 was substituted with an-
other nucleophilic reagent, it reacted with mercaptopyri-
dine derivative to give sulfide derivative 5. The latter com-
pound was cyclized in ethanol in the presence of sodium
ethoxide to afford 3-amino-4,6-dimethyl-2-(N-naphtho-
[2,1-b]furan-2-yl)-thieno[2,3-b]pyridincarboxamide 6
(Scheme I).
3-Aminonaphtho[2,1-b]furan-2-carbohydrazide (8),
prepared by refluxing of 3-ethyl 3-aminonaphtho[2,1-b]-
furan-2-carboxylate (7) with hydrazine hydrate in ethanol,
was used as versatile starting material for the synthesis of
other heterocyclic compounds containing naphthofuran
moiety.
* Corresponding author. E-mail: a.eldean@acc.aun.edu.eg

1046 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Badr et al.
Scheme I
Treatment of carbohydrazide 8 with sodium nitrite in
acetic acid produced 3-aminonaphtho[2,1-b]furan-2-car-
boazide 9. Upon heating, the produced carboazide deriva-
tive 9 in xylene underwent Curtius rearrangement to give
naphthofuroimidazole derivative 10 (Scheme II).
13. While when allowed to react with CS2 in pyridine, 2-
(naphtho[2,1-b]furan-2-yl)-5-mercaptooxadiazole 14 was
produced.
Other naphthofuropyrimidines (15-17) were synthe-
sized from carbohydrazide 8. 3-Formylaminonaphtho-
[1¢,2¢:4,5]furo[3,2-d]pyrimidin-4-one 15 was prepared by
refluxing carbohydrazide 8 with formic acid, while 3-eth-
oxymethyleneaminonaphtho[1¢,2¢:4,5]furo[3,2-d]pyrimi-
din-4-one 16 was prepared by refluxing carbohydrazide 8
with triethyl orthoformate in the presence of a catalytic
amount of acetic acid.
The carbohydrazide 8 underwent condensation reac-
tion with acetyl acetone in ethanol to afford naphtho[2,1-
b]furan-2-yl-pyrazol-1-yl-ketone 11. Also it was condensed
with aromatic aldehydes in ethanol in the presence of a cat-
alytic amount of acetic acid to give the corresponding car-
bohydrazones 12. The produced carbohydrazone 12 was
reacted with triethyl orthoformate which cyclized to 3-aryl
hydrazononaphtho[1¢,2¢:4,5]furo[3,2-d]pyrimidin-4-one
Also 3-diacetylaminonaphtho[1¢,2¢:4,5]furo[3,2-d]-
pyrimidin-4-one 17 was prepared by refluxing carbohydra-

Synthesis and Reactions of Naphthofurans
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1047
zide 8 with acetic anhydride.
Scheme II
EXPERIMENTAL
Melting points were uncorrected and determined us-
ing a Kofler melting point apparatus. IR spectra were re-
corded on a Pye Unicam SP 3-100 spectrometer using the
KBr Wafer technique. 1H NMR spectra were recorded on a
Varian EM-390 90 MHz and Joel 400 MHz spectrometers
in a suitable deuteriated solvent using TMS as internal stan-
dard. Mass spectra were recorded on a Joel MS600 mass
spectrometer. 2-Hydroxynapthonitrile was prepared ac-
cording to a literature procedure.12
Scheme III
Scheme IV

1048 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Badr et al.
N-(2-Acetylnaphtho[2,1-b]furan-1-yl)-2-chloroacet-
amide (3a)
Produced as yellow crystals 2.72 g; 90% yield; m.p.
188-90 °C.
Anal. Calc. for C16H12ClNO3 (301.73): C, 63.69; H,
2-Amino-4-methyl-naphtho[1¢,2¢:4,5]furo[3,2-b]pyri-
dine-3-carbonitrile 2a
A mixture of compound 1a (2.25 g, 0.01 mol), (0.66
g, 0.01 mol) malononitrile, and few drops of piperidine in
ethanol (30 mL) was heated under reflux for 3 h, then al-
lowed to cool. The solid product was collected and recrys-
tallized from DMF as yellow crystals 1.8 g, 66% yield, m.p.
> 300 °C.
4.01; Cl, 11.75; N, 4.64%.
Found: C, 63.54; H, 3.81; Cl, 11.97; N, 4.80%.
IR: n = 3260 cm-1 (NH), 1700, 1680 cm-1 (2C=O).
1H NMR (DMSO-d6): d = 2.35 (s, 3H, CH3), 4.2 (s,
2H, CH2), 7.7-8.0 (m, 6H, Ar-H) and at 9.25 (s, 1H, NH).
Anal. Calc. for C17H11N3O (273.29): C, 74.71; H,
4.06; N, 15.38%.
Found: C, 74.94; H, 3.88; N, 15.25%.
IR: n = 3390, 3290 cm-1 (NH2), and 2220 cm-1 (CN).
1H NMR (DMSO-d6): d = 2.65 (s, 3H, CH3), 6.5 (s,
2H, NH2), and at 7.6-8.5 (m, 6H, Ar-H).
13C NMR of 2a 15 signals at 116-155 for aromatic
rings carbons, at 15.6, 25.5 2 signals for C-(CH3) carbons
and at 115.3 s for -CN carbons.
2-Benzoyl-3-chloroacetylaminonaphtho[2,1-b]furan
(3b)
Produced as yellow crystals 3.45 g; 95% yield, m.p.
200 °C.
Anal. Calc. for C16H12ClNO3 (363.80): C, 69.33; H,
3.88; Cl, 9.75; N, 3.85%.
Found: C, 69.09; H, 4.11; Cl, 9.98; N, 4.07%.
IR: n = 3250 cm-1 (NH), 1700, 1670 cm-1 (2C=O).
1H NMR (DMSO-d6): d = 4.3 (s, 2H, CH2), 7.2-8.0
(m, 11H, Ar-H) and at 10.5 (s, 1H, NH).
3-Cyano-4-methyl-naphtho[1¢,2¢:4,5]furo[3,2-b]pyri-
dine-2(1H)-one 2b
A mixture of 2-acetyl-3-aminonaphthofuran 1a (1.12
g, 0.005 mol), ethyl cyanoacetate (1.13 g, 0.01 mol) and
ammonium acetate (3.35 g, 0.05 mol) was fused on a heater
for one hour, then acetic acid (15 mL) was added and the
mixture was refluxed for 2 h. The solid product was col-
lected and recrystallized from DMF as yellow crystals
(0.85 g, 62% yield), m.p. > 300 °C.
N-[2-Acetyl(bezoyl)-naphtho[2,1-b]furan-3-yl]-2-aryl
(alkyl)aminoacetamide (4a-d)
A mixture of compound 3a (3.017 g, 0.01 mol), pri-
mary or secondary amine (0.01 mol) and potassium carbon-
ate (2.76 gm, 0.02 mol) in ethanol (30 mL) was refluxed for
5 hrs, then allowed to cool and poured into water (100 mL).
The solid precipitate was filtered off, dried and recrystal-
lized from ethanol.
Anal. Calc. for C17H10N2O2 (274.28): C, 74.45; H,
3.67; N, 10.21%.
Found: C, 74.22; H, 3.48; N, 10.00%.
IR: n = 3490 cm-1 (NH), 2220 cm-1 (CN) and at 1640
cm-1 (-C=O).
N-(2-Benzoyl-naphtho[2,1-b]furan-3-yl)-2-phenylamino-
acetamide (4a)
1H NMR (DMSO-d6): d = 2.55 (s, 3H, CH3), 7.7-9.0
Obtained from 3b and aniline as green crystals 3.38 g,
80.5% yield; m.p. 110-112 °C.
(m, 6H, Ar-H) and at 9.25 (s, 1H, NH).
Anal. Calcd. for C27H20N2O3 (420.47): C, 77.13; H,
4.79; N, 6.66%.
Chloroacetylation of 2-acetyl(benzoyl)-3-aminonaph-
tho[3,2-b]furan (General procedure)
Found: C, 76.89; H, 5.00; N, 6.52%.
IR: n = 3350, 3200 cm-1 (2NH), 1690, 1670 cm-1
(2C=O).
To a solution of compound 1a (2.25 g, 0.01 mol) or 1b
(2.87 g, 0.01 mol) in dioxian (20 mL), chloroacetyl chlo-
ride (1.12 g, 0.01 mol) was added. The mixture was heated
on a steam bath at 70 °C for 3 h, allowed to cool and poured
into cold water (100 mL), then the mixture was neutralized
with sodium carbonate solution (10%) until reach to just al-
kaline. The solid product was collected and recrystallized
from ethanol.
1H NMR (DMSO-d6): d = 4.0 (s, 2H, CH2), 7.0-8.2
(m, 16H, Ar-H) and at 8.5, 10.5 (2s, 2H, 2NH).
N-(2-Benzoyl-naphtho[2,1-b]furan-3-yl)-2-p-tolylamino-
acetamide (4b)
Obtained from 3b and p-toluidine as green crystals

Synthesis and Reactions of Naphthofurans
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1049
3.61 g, 83% yield; m.p. 140 °C.
Anal. Calcd. for C29H21N3O3S (491.57): C, 70.86; H,
4.31; N, 8.55; S, 6.52%.
Anal. Calcd. for C28H22N2O3 (434.50): C, 77.40; H,
5.10; N, 6.45%.
Found: C, 71.05; H, 4.22; N, 8.73; S, 6.31%.
IR: n = 3350 cm-1 (NH), 3050 cm-1 (CH aromatic),
2220 cm-1 (CN), and at 1690 cm-1 (CO).
1H NMR (DMSO-d6): d = 2.3 (s, 3H, CH3), 2.7 (s, 3H,
CH3), 4.0 (s, 2H, CH2), 7.0 (s, 1H, CH-pyridine), 7.3-8.4
(m, 11H, Ar-H) and at 10.9 (s, H, NH).
Found: C, 77.59; H, 4.91; N, 6.57%.
IR: n = 3340, 3250 cm-1 (2NH), 1690, 1670 cm-1
(2C=O).
1H NMR (DMSO-d6): d = 2.3 (s, 3H, CH3), 4.0 (s, 2H,
CH2), 7.0-8.2 (m, 15H, Ar-H) and at 8.5, 10.5 (2s, 2H,
2NH).
3-Amino-4,6-dimethyl-2-N-(2-benzoyl-naphtho[2,1-b]-
furan-1-yl)thieno[2,3-b]pyridine carboxamide 6
To a solution of (5) (245 mg, 0.0005 mol) in ethanol
(20 mL), a few drops of sodium ethoxide solution were
added. The mixture was refluxed for 1 hr and left to cool.
The solid product obtained on dilution with water was fil-
tered off, dried and recrystallized from ethanol as orange
crystals in 79% yield; m.p. 274-276 °C.
N-(2-Benzoyl-naphtho[2,1-b]furan-3-yl)-2-(N-pipredinyl)-
acetamide (4c)
Obtained from 3b and piperidine as pale yellow crys-
tals, m.p. 130 °C in Yield 78%.
Anal. Calcd. for C26H24N2O3 (412.49): C, 75.71; H,
5.86; N, 6.79%.
Found: C, 75.48; H, 6.20; N, 7.01%.
IR: n = 3050 cm-1 (CH aromatic), 2950 cm-1 (CH
aliphatic), 1690 cm-1 (CO) and at 3350 cm-1 (NH).
1H NMR (CDCl3): d = 1.3-1.5 (m, 6H, 3CH2), 2.3 (m,
4H, 2CH2), 2.4 (s, 2H, CH2), 7.3-8.4 (m, 11H, Ar-H) and at
10.5 (s, H, NH).
Anal. Calcd. for C29H21N3O3S (491.57): C, 70.86; H,
4.31; N, 8.55; S, 6.52%.
Found: C, 7.73; H, 4.55; N, 8.23; S, 6.71%.
IR: n = 3450, 3310 cm-1 (NH2), 3050 cm-1 (CH aro-
matic), and at 1680 cm-1 (CO).
1H NMR (DMSO-d6): d = 2.3 (s, 3H, CH3), 2.7 (s, 3H,
CH3), 6.0 (s, 2H, NH2), 7.0 (s, 1H, CH-pyridine), 7.3-8.4
(m, 11H, Ar-H) and at 10.9 (s, H, NH).
N-(2-Benzoyl-naphtho[2,1-b]furan-3-yl)-2-(N-mor-
pholinyl)-acetamide (4d)
Obtained from 3b and morpholine as pale yellow
crystals in 63% yield, m.p. 82 °C.
Ethyl 3-Amino-naphtho[2,1-b]furan-2-carboxylate (7)
Was prepared according to the procedure reported in a
previous work.13
Anal. Calcd. for C25H22N2O4 (414.47): C, 72.45; H,
5.35; N, 6.76%.
Found: C, 72.38; H, 5.52; N, 7.00%.
IR: n = 3050 cm-1 (CH aromatic), 2950 cm-1 (CH
aliphatic), 1690 cm-1 (CO) and at 3350 cm-1 (NH).
1H NMR (CDCl3): d = 2.3-2.5 (m, 4H, 3CH2), 3.3-3.5
(m, 4H, 2CH2), 3.9 (s, 2H, CH2), 7.3-8.4 (m, 11H, Ar-H)
and at 11.5 (s, H, NH).
3-Aminonaphtho[2,1-b]furan-2-carboxylic hydrazide
(8)
Ethyl 3-amino-naphtho[2,1-b]furan-2-carboxylate
(7) (5 gm, 0.02 mol) and hydrazine hydrate (2 mL, 0.04
mol) in ethanol (20 mL) was refluxed for 3 hrs., then al-
lowed to cool. The solid precipitate was collected and
recrystallized as yellow crystals in 71% yield; m.p. 158-
160 °C.
[N-(2-Benzoyl-naphtho[2,1-b]furan-1-yl)-aminomethyl]-
[3-cyano-4,6-dimethylpyridin-2-yl]-sulfide 5
A mixture of N-(2-acetyl-naphtho[2,1-b]furan-1-yl)-
2-chloro-acetamide (3b) (0.75 g, 0.0025 mol), anhydrous
sodium acetate (0.41 g, 0.005 mol) and 4,6-dimethyl-2-
mercaptopyridin-3-carbonitrile (0.41 g, 0.0025 mol) in eth-
anol (30 mL) was heated under reflux for 3 h, then allowed
to cool. The solid precipitate was filtered off, washed with
water several times, dried and recrystallized from ethanol,
in 85% yield, m.p. 190-192 °C.
Anal. Calcd. for C13H11N3O2 (241.25): C, 64.72; H,
4.60; N, 17.42%.
Found: C, 64.49; H, 4.82; N, 17.21%.
IR: n = 3450, 3350, 3200 cm-1 (NHNH2, NH) and
1670 cm-1 (C=O).
1H NMR (DMSO-d6): d = 3.8 (s, 2H, hydrazide NH2),
5.9 (s, 2H, NH2), 7.2-7.9 (m, 6H, Ar-H) and at 9.5 (s, 1H,
NH).

1050 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Badr et al.
3-Aminonaphtho[2,1-b]furan-2-carboxylic azide (9)
Sodium nitrite solution (5.5 mL 5%, 0.04 mol) was
added to a solution of 3-aminonaphtho[2,1-b]furan-2-car-
bohydrazide (8) (2.41 gm, 0.01 mol) in acetic acid (10 mL)
at room temperature over 5 minutes with stirring. The solid
product was filtered off, dried, and collected as buff crys-
tals; in 60% yield, m.p. 140 °C and used without further pu-
rification.
and an appropriate aromatic aldehyde (0.005 mol) in etha-
nol (20 mL), a few drops of acetic acid was added. The mix-
ture was heated under reflux for 3 h, then allowed to cool.
The solid product was collected and recrystallized from di-
oxan.
Benzyledine 3-aminonaphtho[2,1-b]furan-2-carbohy-
drazone (12a)
Produced in 91% yield; m.p. 240-242 oC.
Anal. Calcd. for C20H15N3O2 (329.36): C, 72.94; H,
4.59; N, 12.76%.
Anal. Calcd. for C13H8N4O2 (252.23): C, 61.90; H,
3.20; N, 22.21%.
Found: C, 64.49; H, 4.82; N, 17.21%.
IR: n = 3350, 3250 cm-1 (NH2), 2200 cm-1 (N3) and
1710 cm-1 (C=O).
Found: C, 73.18; H, 4.71; N, 12.92%.
IR: n = 3450, 3310, 3270 cm-1 (NH, NH2), and 1690
cm-1 (C=O).
1H NMR (CDCl3): d = 5.9 (s, 2H, NH2) and 7.2-7.9
(m, 6H, Ar-H).
1H NMR (DMSO-d6): d = 6.0 (s, 2H, NH2), 7.2-8.4
(m, 11H, Ar-H), 8.8 (s, 1H, CH=N-), and 11.05 (s, 1H, NH).
1,3-Dihydro-naphtho[2¢,1¢:2,1]imidazol-2-one (10)
3-Aminonaphtho[2,1-b]furan-2-carbonylazide (9)
(0.5 gm) in xylene (20 mL) was heated under reflux for 1 hr.
The solid product was filtered off and washed several times
with xylene. Dried and recrystallized from xylene as brown
crystals (0.4 gm) in 90% yield, m.p. > 360 °C.
Anal. Calcd. for C13H8N2O2 (224.22): C, 69.64; H,
3.60; N, 12.49%.
4-Methoxy-benzyledine 3-aminonaphtho[2,1-b]furan-2-
carbohydrazone (12b)
Obtained from carbohydrazide 8 and 4-methoxy-
benzaldehyde in 89% yield; m.p. 234-236 °C.
Anal. Calcd. for C21H17N3O3 (359.39): C, 70.18; H,
4.77; N, 11.69%.
Found: C, 69.99; H, 5.02; N, 11.47%.
IR: n = 3440, 3320, 3250 cm-1 (NH, NH2), and 1690
cm-1 (C=O).
Found: C, 69.40; H, 3.38; N, 12.73%.
IR: n = 3310, 32300 cm-1 (2NH), and 1670 cm-1
(C=O).
1H NMR (CDCl3): d = 7.2-7.9 (m, 6H, Ar-H) and 9.9
(s, 2H, 2NH).
1H NMR (DMSO-d6): d = 3.9 (s, 3H, CH3), 5.8 (s, 2H,
NH2), 7.0-8.5 (m, 10H, Ar-H), 8.6 (s, 1H, CH=N-), and
11.5 (s, 1H, NH).
[3-Amino-naphtha[2,3-b]furan-2-yl]-[3,5-dimethylpyr-
azol-1-yl]ketone 11
4-Chloro-benzyledine 3-aminonaphtho[2,1-b]furan-2-
carbohydrazone (12c)
A mixture of carbohydrazide (8) (0.5 gm, 0.002 mol)
and acetylacetone (0.4 mL, 0.004 mol) was refluxed in eth-
anol for 4 hrs. On cooling the preciptated solid which
formed was filtered off and recrystallized from ethanol as
pale yellow needles, m.p. 215-217 °C; yield 94%.
Anal. Calcd. for C18H15N3O2 (305.34): C, 70.81; H,
4.95; N, 13.76%.
Obtained from carbohydrazide 8 with 4-chlorobenz-
aldehyde in 84% yield; m.p. 248-250 °C.
Anal. Calcd. for C20H14ClN3O2 (363.81): C, 66.03; H,
3.88; Cl, 9.75; N, 11.55%.
Found: C, 65.89; H, 4.05; Cl, 9.94; N, 11.72%.
IR: n = 3390, 3290, 3250 cm-1 (NH, NH2), and 1750
cm-1 (C=O).
Found: C, 71.00; H, 5.18; N, 13.92%.
1H NMR (DMSO-d6): d = 5.9 (s, 2H, NH2), 7.3-8.4
IR: n = 3350, 3250 cm-1 (NH2), and 1690 cm-1 (C=O).
1H NMR (CDCl3): d = 2.9 (s, 6H, 2CH3), 5.5 (s, 1H,
CH-pyrazole), 6.0 (s, 2H, NH2), 7.2-7.9 (m, 6H, Ar-H).
(m, 10H, Ar-H), 8.7 (s, 1H, CH=N-), and 10.9 (s, 1H, NH).
3-Aryledineaminonaphtho[3¢,2¢:4,5]furo[3,2-d]pyrimi-
dine-4(3H)-one (13a-c) General procedure
Arylidene 3-aminonaphtho[2,1-b]furan-2-carbohydra-
zone (12a-c) General procedure
A mixture of (12a-c) (0.002 mol) and triethyl ortho-
formate (5 mL) was heated under reflux for 10 minutes in
the presence of a few drops of acetic acid (2-3 mL). The
To a mixture of carbohydrazide 8 (1.2 g, 0.005 mol)

Synthesis and Reactions of Naphthofurans
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1051
solid product which formed on hot was collected and re-
IR: n = 3340, 3240 cm-1 (NH2), 3050 cm-1 (CH, aro-
matic), and 1220 cm-1 (S-H).
crystallized from dioxan as white crysals of (13a-c).
1H NMR (DMSO-d6): d = 3.5 (s, 1H, SH), 5.95 (s, 2H,
3-Benzyledineaminonaphtho[3¢,2¢:4,5]furo[3,2-d]pyrimi-
dine-4(3H)-one (13a)
NH2), 7.0-8.1 (m, 6H, Ar-H).
Obtained from (12a) in 92% yield; m.p. 225-227 °C.
Anal. Calcd for C21H13N3O2 (339.36): C, 74.33; H,
3.86; N, 12.38%.
3-Formylaminonaphtho[3¢,2¢:4,5]furo[3,2-d]pyrimi-
dine-4(3H)-one (15)
3-Aminonaphtho[2,1-b]furan-2-carbohydrazide (0.5
gm) in formic acid (10 mL) was refluxed for 4 hrs. On cool-
ing the precipitated solid was filtered off and recrystallized
from ethanol as white needles in 60% yield; m.p. 290-292
°C.
Found: C, 74.18; H, 4.04; N, 12.49%.
IR: n = 3050 cm-1 (CH, aromatic), and 1685 cm-1
(C=O).
1H NMR (DMSO-d6): d = 7.2-8.4 (m, 11H, Ar-H),
8.9, 9.1 (2s, 1H, CH=N- and CH pyrimidine).
Anal. Calcd for C15H9N3O3 (279.26): C, 64.52; H,
3.25; N, 15.05%.
3-(p-Methoxybenzylideneamino)-naphtho[3¢,2¢:4,5]furo-
[3,2-d]pyrimidine-4(3H)-one (13a)
Obtained from (12b) in 95% yield; m.p. 248-250 °C.
Anal. Calcd for C22H15N3O3 (369.38): C, 71.54; H,
4.09; N, 11.38%.
Found: C, 64.69; H, 3.44; N, 14.83%.
IR: n = 3400 cm-1 (NH), 3050 cm-1 (CH, aromatic),
and 1710, 1690 cm-1 (2C=O).
1H NMR (DMSO-d6): d = 7.2-8.4 (m, 8H, Ar-H, 1H,
CH=N- and CH pyrimidine), 8.9 (s, 1H, CH formyl) and
9.9 (s, 1H, NH).
Found: C, 71.31; H, 3.88; N, 11.51%.
IR: n = 3050 cm-1 (CH, aromatic), and 1680 cm-1
(C=O).
1H NMR (DMSO-d6): d = 3.5 (s, 3H, CH3), 7.0-8.2
(m, 10H, Ar-H), 9.2, 9.5 (2s, 1H, CH=N- and CH pyrimi-
dine).
3-Ethoxymethyleneaminonaphtho[2¢,1¢,4,5]furo[3,2-d]-
pyrimidine-4(3H)-one (16)
A mixture of carbohydrazide (8) (0.3 gm, 0.001 mol)
and triethylorthoformate (3 mL) was refluxed for 15 min-
utes in the presence of a few drops of glacial acetic acid
(2-3 drops). The solid that formed on hot was collected and
recrystallized from DMF as clear white crystals in 76%
yield; m.p. 170-171 °C.
3-(p-Chloro)-benzyledineaminonaphtho[3¢,2¢:4,5]furo-
[3,2-d]pyrimidine-4(3H)-one (13c)
Obtained from 12c in 93% yield; m.p. 289-290 °C.
Anal. Calcd. for C21H12ClN3O2 (373.80): C, 67.48; H,
3.24; Cl, 9.48; N, 11.24%.
Anal. Calcd. for C17H13N3O3 (307.31): C, 66.44; H,
4.26; N, 13.67%.
Found: C, 67.29; H, 3.01; Cl, 9.71; N, 11.46%.
IR: n = 3050 cm-1 (CH, aromatic), and 1690 cm-1
(C=O).
Found: C, 66.61; H, 4.50; N, 13.44%.
IR: n = 3050 cm-1 (CH, aromatic), 2950 cm-1 (CH,
aliphatic), and 1690 cm-1 (C=O).
1H NMR (DMSO-d6): d = 1.15 (t, 3H, CH3), 3.6 (q,
2H, CH2), 7.2-8.4 (m, 8H, Ar-H, 1H, CH=N- and CH py-
rimidine).
1H NMR (DMSO-d6): d = 7.2-8.3 (m, 10H, Ar-H),
8.9, 9.3 (2s, 1H, CH=N- and CH pyrimidine).
2-(Naphtha[2,3-b]furan-2-yl)-5-mercaptooxadiazole 14
A mixture of 3-aminonaphtho[2,1-b]furan-2-carbo-
hydrazide (8) (1 gm) and carbondisulphide (2 mL) was
refluxed in pyridine (4 mL) on a water bath for 12 hrs. A
solid precipitate formed on hot was filtered off and recrys-
tallized from ethanol as buff crystals, in 69% yield, m.p. >
360 °C.
Diacetylaminonaphtho[3¢,2¢:4,5]furo[3,2-d]pyrimidine-
4(3H)-one (17)
3-Aminonaphtho[2,1-b]furan-2-carbohydrazide (0.5
gm) was refluxed in acetic anhydride (20 mL) for 3 hrs. The
solid precipitated on cooling was recrystallized from etha-
nol as white needles in 60% yield; m.p. 240-242 °C.
Anal. Calcd. for C19H15N3O4 (349.35): C, 65.32; H,
4.33; N, 12.03%.
Anal. Calcd. for C14H9N3O2S (283.31): C, 59.35; H,
3.20; N, 14.83; S, 11.32%.
Found: C, 59.14; H, 3.38; N, 15.05; S, 11.51%.
Found: C, 65.09; H, 4.42; N, 11.88%.

1052 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Badr et al.
IR: n = 3050 cm-1 (CH, aromatic), 2950 cm-1 (CH,
aliphatic), and 1690 cm-1 (C=O).
Adebayo, F. O.; Sawickim, D. R.; Seestakkerm, L.; Sullivan,
D.; Taylor, J. R. J. Med. Chem. 2000, 43(7), 1293-1310.
5. Teo, C. C.; Kon, O. L.; Sim, K. Y.; Ng, S. C. J. Med. Chem.
1992, 35(8), 1330-1339.
1H NMR (DMSO-d6): d = 2.1 (s, 3H, CH3), 2.4 (s, 6H,
2CH3), 7.2-8.4 (m, 6H, Ar-H).
6. Maeda, S.; Masuda, H.; Tokoroyama, T. Chem. Pharm. Bull.
1994, 42, 2536-2545.
7. McAllister, G. D.; Hartley, R. C.; Dawson, M. J.; Knaggs, A.
R. J. Chem. Soc. Perkin. Trans. 1 1998, 3453.
Received September 19, 2006.
8. da Silva, A. J. M.; Buarque, D. C.; Brito, F. V.; Aurelian, L.;
Macedo, L. F.; Malkas L. H.; Hickey, R. J.; Lopes, D. V. S.;
Noel, F.; Murakami, Y. L. B.; Silva, N. M. V.; Melo, P. A.;
Caruso, R. R. B.; Castro, N. G.; Costa, P. R. R. Bioorg. Med.
Chem. 2002, 10(8), 2731-2738.
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