Synthesis of some new naphthopyran, pyrazole, pyridine, and thienobenzochromene derivatives using 1-(1-hydroxy-2-naphthyl) ethanone as a versatile starting material

Article abstract of DOI:10.1080/10426500802083158

Treatment of the enaminone 2, prepared from 1-(1-hydroxy-2-naphthyl) ethanone 1 and N,N-dimethylformamide dimethylacetal with acetic acid, thionyl chloride, or bromine, gave the corresponding 4-oxo-4H-naphtho[1,2-b]pyran derivatives 3, 4, and 5. Refluxing

Full text of DOI:10.1080/10426500802083158

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Synthesis of Some
New Naphthopyran,
Pyrazole, Pyridine, and
Thienobenzochromene
Derivatives Using 1-(1-
Hydroxy-2-naphthyl) Ethanone
as a Versatile Starting Material
Doria S. Badawy a , E. M. Kandeel a , Noha M. Awad a
& Abdel-Rahman H. Abdel-Rahman a
a Chemistry Department, Faculty of Science,
Mansoura University, Mansoura, Egypt
Published online: 19 Dec 2008.
To cite this article: Doria S. Badawy , E. M. Kandeel , Noha M. Awad & Abdel-Rahman
H. Abdel-Rahman (2008) Synthesis of Some New Naphthopyran, Pyrazole, Pyridine,
and Thienobenzochromene Derivatives Using 1-(1-Hydroxy-2-naphthyl) Ethanone as a
Versatile Starting Material, Phosphorus, Sulfur, and Silicon and the Related Elements,
184:1, 179-196, DOI: 10.1080/10426500802083158
To link to this article: http://dx.doi.org/10.1080/10426500802083158
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Phosphorus, Sulfur, and Silicon, 184:179–196, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802083158
Synthesis of Some New Naphthopyran, Pyrazole,
Pyridine, and Thienobenzochromene Derivatives
Using 1-(1-Hydroxy-2-naphthyl) Ethanone as a
Versatile Starting Material
Doria S. Badawy, E. M. Kandeel, Noha M. Awad, and
Abdel-Rahman H. Abdel-Rahman
Chemistry Department, Faculty of Science, Mansoura University,
Mansoura, Egypt
Treatment of the enaminone 2, prepared from 1-(1-hydroxy-2-naphthyl)ethanone
1 and N,N-dimethylformamide dimethylacetal with acetic acid, thionyl chloride,
or bromine, gave the corresponding 4-oxo-4H-naphtho[1,2-b]pyran derivatives 3,
4, and 5. Refluxing of p-toluidine or p-anisidine with 2 afforded compounds 6
and 7, respectively. The naphtho[1,2-b]pyran-3-carbaldehyde 9 was prepared via
the acetylation of 2. Condensation of 9 with malononitrile or ethyl cyanoacetate
gave the pyridine derivatives 10 and 11. Refluxing of 9 with hydrazine hydrate,
phenylhydrazine, semicarbazide hydrochloride, or thiosemicarbazide afforded
the pyrazole derivatives 12, 13, 14, and 15 respectively. Reaction of ethanone 1
with malononitrile gave the chromene carbonitrile derivative 16. Treatment of
16 with malononitrile afforded the chromene malononitrile derivative 17. Also,
compound 17 was obtained from the reaction of 1 with excess of malononitrile and
catalytic piperidine. Treatment of 16 with ethyl cyanoacetate produced compound
18. When 16 was treated with elemental sulfur, theino[3,4-c]benzochromene
derivative 19 was produced. Hydrolysis of 16 with hydrochloric acid yielded
the benzochromene carbonitrile derivative 20 which on heating with elemental
sulfur afforded the theinobenzochromene derivative 21. Treatment of 21 with
acetic anhydride, p-chlorobenzaldehyde, phenyl isothiocyanate, or thionylchloride
furnished compounds 22, 23, 24, and 25, respectively.
Keywords Naphtho[1,2-b]pyran; naphtho[1,2-b] pyran-3-carbaldehyde; thieno[3,4-
c]benzochromene
INTRODUCTION
Benzopyran derivatives show a wide variety of applications as biolog-
ical active compounds in medicine,1–5 and bactericides6 and useful as
Received 23 January 2008; accepted 27 March 2008.
Address correspondence to Dr. Abdel-Rahman H. Abdel-Rahman, Chemistry Depart-
ment, Faculty of Science, Mansoura University, Mansoura, Egypt. E-mail: dr abdel-
rahman@hotmail.com
179

180
D. S. Badawy et al.
antiphogistics, antipyretics, and analgesics.7 It is well known that some
benzopyran derivatives possess coronary vasolidating activity.8–10 Re-
cently, benzopyran derivatives are shown to possess desirable altering
activity for example, decreasing the atherogenic VLDL+LDL choles-
terol fraction.11–16 Also, benzopyran derivatives produced crosslinks
in photoreaction with DNA.17 Thus, the high pharmacological interest
of the above-mentioned derivatives encouraged us to synthesize some
new benzopyran derivatives and carry out some reactions on them in
order to obtain more potent biological activity.
RESULTS AND DISCUSSION
Our endeavors in this regard started with 1-(1-hydroxy-
2-naphthyl)ethanone (1), which upon treatment with N,N-
dimethylformamide dimethylacetal, afforded the enaminone (2E)-
3-dimethylamino)-1-(1-hydroxy-2-naphthyl)prop-2-en-1-one (2) in
excellent yield (90%).18,19 In the IR spectrum, 2 showed an OH band
1
at 2950 and the C O band at 1643 cm−1. In the H-NMR spectrum, 2
showed two doublets at δ = 5.9 and 8.4 ppm, J = 11.8 Hz, due to trans
CH CH and two signals at 3 and 3.2 ppm due to N(CH3)2. Preparation
and some reactions of 2 are summarized in Scheme 1.
SCHEME 1

Synthesis of New Derivatives Using 1-(1-Hydroxy-2-naphthyl) Ethanone
181
It was reported that treatment of o-hydroxyl aryl enaminones in
acidic conditions caused cyclization and formation of the corresponding
chromones.20 So, when the enaminone 2 was boiled in acetic acid, ring
closure with elimination of dimethyl amine occurred, and 4-oxo-4H-
naphtho[1,2-b]pyran (3) was formed in excellent yield (91%). Its struc-
ture was established on the basis of its spectral data. The IR spectrum
showed an absoption band at 1639 cm−1 characteristic for a carbonyl
1
group, and the H-NMR spectrum showed two doublets at δ = 6.5, 8.1
ppm, characteristic for the 2-H and 3-H of the chromone ring. The mass
spectrum gave a molecular ion peak [M+] at m/z = 196.
Treatment of 2 with thionyl chloride in dry benzene afforded 4-oxo-
4H-4-naphtho[1,2-b]pyran-3-sulfinic acid (4) (60%). The IR spectrum of
compound 4 displayed a band at 1190 cm−1 characterstic for the (SO2)
1
group, and the H-NMR spectrum revealed the presence of 1-H as a
singlet moderately downfield at δ = 8.51 ppm.
Also, the enaminone 2 was treated with bromine at 40◦C to give
2,3-dibromo-4-oxo-4H-naphtho[1,2-b]pyran (5) (55%). Its structure was
1
established on the basis of elemental analysis and its H-NMR and
mass spectra. In the1H-NMR spectrum, 5 showed the disappearance of
the two doublet signals characteristic for the chromone ring. The mass
spectrum of 5 gave three molecular ion peaks [M+] at m/z = 351, 353,
and 355.
When compound 2 was reacted with p-toluidine in boiling ethanol,
(2E)-3-p-tolylamino-1-(1-hydroxynaphthyl)-2-propenone (6) was ob-
tained. The structure of 6 was supported by the spectral data. Its IR
spectrum showed a band at 1649 cm−1 characteristic for a carbonyl
1
group, and the H-NMR spectrum exhibited the disappearance of the
two singlets characteristic for the two methyl groups of the parent
compound and the presence of one singlet at δ 2.3 ppm for the methyl
protons of p-toluidine.
Similarly, the enaminone 2 reacted with p-anisidine in ethanol to
give (2E)-3-p-anisylamino-1-(1-hydroxynaphthyl)-2-propenone (7). Its
IR spectrum displayed a band at 1649 cm−1 for a carbonyl group, and
its 1H-NMR spectrum revealed a singlet at δ = 3.9 ppm for the methoxy
protons.
In an attempt to prepare 3-acetyl-4-oxo-4H-naphtho[1,2-b]pyran (8)
via the acetylation of compound 2,21 2-methyl- 4-oxo-4H-naphtho[1,2-
b]pyran-3-carbaldehyde (9) was obtained as the sole product without
formation of the expected (8).
The reaction mechanism as shown in Scheme 2 may proceed via the
acetylation of the phenolic OH group followed by an intramolecular
ester condensation, followed by ring closure to give 2-methyl-4-oxo-4H-

182
D. S. Badawy et al.
SCHEME 2
naphtho[1,2-b]pyran-3-carbaldehyde (9). Support for the formation of
the carbaldehyde 9 came from the IR absorption at 1682 cm−1 (CHO)
1
group and 1641 cm−1(C O of the γ-pyrone ring) and the H-NMR sig-
nals at δ = 2.6(s, 3H, CH3), 10.50(s, 1H, CHO). The mass spectrum gave
a molecular ion at peak [M+] at m/z = 238.
Treatment of 9 with malononitrile or ethylcyanoacetate in the
presence of ammonium acetate caused cleavage of the pyran ring
and subsequent pyridine formation to give 5-(1-hydroxy-2-naphthoyl)-
2-amino-4-methyl-3-carbonitrile (75%) (10) and ethyl 5-(1-hydroxy-2-
naphthyl)-2-amino-4-methyl-3-carbonate (11) (52%) (Scheme 3). The
structure of 10, was supported by the spectral data. The IR spectrum
revealed absorption bands at 3397–3333 cm−1 (NH2) and 2219 cm−1
1
(CN) group), the H-NMR spectrum showed a singlet at δ 2.45(4-CH3)
and a signal at δ 8.5 ppm (6-H in pyridine ring), and the mass spectrum
gave a molecular ion peak [M+] at m/z = 303. The IR spectrum of 11
showed absorption bands at 3493, 3432 (NH2), 1725 cm−1 (C O-ester);
the 1H-NMR spectrum showed signals at δ = 2.75 (4-CH3) and 8.6 pmm
(6-H in pyridine); and the mass spectrum gave a molecular ion peak
[M+] at m/z = 350.
Treatment of
9 with hydrazine, phenylhydrazine, semicar-
bazide, or thiosemicarbazide in ethanol also caused the pyran ring
cleavage and subsequent pyrazole formation to give 4-(1-hydroxy-2-
naphthoyl)-5-methylpyrazole (12) (70%), 4-(1-hydroxy-2-naphthoyl)-
5-methyl-1-phenylpyrazole (13) (65%), 4-(1-hydroxy-2-naphthoyl)-
5-methylpyrazole-1-carbamide (14) (60%), and 4-(1-hydroxy-2-
naphthoyl)-5-methylpyrazole-1-thiocarbamide (15) (72%). The struc-
tures of 12, 13, 14, and 15 were supported by the spectral data; the
C O bands around 1645–1637 and the C N bands around 1627–1567
cm−1 in the IR spectra, three singlets around δ 2.0–2.9 (5-CH3 in
pyrrole) and 8.35–8.60 (3-H in pyrrole), and 10.5–11.6 ppm (hydrogen
1
bonded OH) in the H-NMR spectra. The mechanism for 12, 13, 14,
and 15 might be explained as shown in Scheme 4.

Synthesis of New Derivatives Using 1-(1-Hydroxy-2-naphthyl) Ethanone
183
SCHEME 3
In continuation of our investigation on the synthesis of polyhete-
rocyclic systems of biological interest using 1-(1-hydroxy-2-naphthyl)
ethanone 1, 2-imino-4-methyl-2Hbenzo[h] chromene-3-carbonitrile
(16), which provided easy access to polycyclic systems, was obtained
via the interaction 1-(1-hydroxy-2-naphthyl)ethanone 1 with malonon-
itrile in the presence of sodium ethoxide (Scheme 5). The structure of
compound 16 was assigned on the basis of its analytical and spectral
data. The IR spectrum showed the absence of the acetyl (CO) group
and showed a band at 2225 cm−1 characteristic for the (CN) group. The
1H-NMR spectrum showed a signal at δ 6.45 (s, IH) ppm, and the mass
spectrum gave a molecular ion peak [M+] at m/z = 234, which was in
agreement with its molecular weight.
When compound 16 was reacted with malononitrile (1:1 stoichio-
metric ratio) in the presence of catalytic piperidine, [amino(2-imino-
4-methyl-2H-benzo[h]chromen-3-yl)methylene] malonontrile (17) was
obtained (Scheme 6). The IR spectrum of 17 exihibited two bands at
2221 and 2206 cm−1 characteristic for (2CN) groups. Also compound
17 was produced from the reaction of 1 with excess malononitrile and
catalytic piperidine.

184
D. S. Badawy et al.
SCHEME 4
SCHEME 5
The reaction of 16 with ethyl cyanoacetate in ethanol gave (2Z)-3-
amino-2-cyano-3-(2-imino-4-methyl-2H-benzo[h] chromen-yl) acrylate
(18) (Scheme 7). Its IR spectrum displayed a band at 1720 cm−1 char-
acteristic for the (CO-ester) group .The 1H-NMR spectrum showed sig-
nals at δ 1.45 (t, 3H, CH3 ester), 4.45 (q, 2H, CH2 ester), 8,6 (br.s, NH),
8.96 (br.s, 1H, NH) and 9.06 ppm (br.s, NH). The mass spectrum of 18
gave a molecular ion peak [M+] at m/z = 347 which was in agreement
with its molecular weight.
Alternatively, the interaction of 16 with elemental sulfur in ethanolic
morpholine yielded 4-imino-4H-thieno[3,4-c]benzo[h] chromen-3 amine
(19), which formed via the thiation of the methyl group of (16), form-
ing an intermediate followed by interamolecular cyclization as shown
in Scheme 7. The assigned structure of compound 19 was based on
its analytical and spectral data, the IR spectrum that showed the ab-
1
sence of (CN) group, the H-NMR spectrum that showed the absence
of the methyl group and gave a singlet at δ 6.96 ppm characteristic for

Synthesis of New Derivatives Using 1-(1-Hydroxy-2-naphthyl) Ethanone
185
SCHEME 6
SCHEME 7
SCHEME 8
1H-thiol, and the mass spectrum gave a molecular ion peak [M+] at
m/z = 266, which was in agreement with its molecular weight.
The hydrolysis of the imine 16 to the oxo deritavives yielded 4-
methyl-2-oxo-2H-benzo[h] chromene-3-carbonitrile (20). The IR spec-
trum of 20 showed an absorption band at 1726 cm−1 characteristic for
a (CO) group and the mass spectrum gave a molecular ion peak [M+]
at m/z = 235 which was in agreement with its molecular weight.
The reaction of 20 with elemental sulfur in ethanol gave 3-amino-4H-
thieno[3,4-c] benzo[h] chromen-4-one (21) through the thiation of the
methyl group of 16, followed by interamlecular cyclization as shown
in Scheme 8. The structure of 21 was confirmed by its IR spectrum,
which showed the absence of the (CN) group and the presence of the
1
(CO) group at 1677 cm−1; the H-NMR spectrum revealed signals at
δ 6.95 (s, 1H, thiophene), 7.3–8.6 ppm (m, 8H, Ar-H; NH2); and the mass

186
D. S. Badawy et al.
SCHEME 9
spectrum gave a molecular ion peak [M+] at m/z = 267, which was in
agreement with its molecular weight.
The behavior of 3-amino thieno compound 21 towards different
reagents was investigated as shown in Scheme 9. Thus, acetylation
of 21 with acetic anhydride consumed one mole of acetic anhydride
to form N-(4-oxo- 4H-thieno[3,4-c]benzo[h]chromen-yl) acetamide (22).
The IR spectrum of compound 22 exhibited a broad absorption band at
1
1680 cm−1 for the (2CO) groups, and the H-NMR spectrum showed a
signal at δ 2.3 pmm (s, 3H, CH3).
Also, the corresponding Schiff base (23) was obtained from the re-
action of 21 with p-chlorobenzaldehyde in ethanolic piperidine. The IR
spectrum of 23 revealed the disappearance of the bands characteristic

Synthesis of New Derivatives Using 1-(1-Hydroxy-2-naphthyl) Ethanone
187
for the NH2group, and bands appeared at 1677 cm−1 (CO) and
1599 cm−1 for the (C N), and the mass spectrum exhibited a molec-
ular ion peak [M+] at m/z = 389.6, which was in agreement with its
molecular weight.
Furthermore, interaction of 21 with phenyl isothiocyanate under re-
flux in ethanolic triethylamine led to the formation of N-(4-imino-4H-
thieno [3,4-c]benzo[h]chromen-3-yl) ethanethioamide (24). The IR spec-
trum of (24) displayed absorption bands at 3297, 3160 (2NH), 1677(CO),
and 1263 cm−1 for the (C S) group; the 1H-NMR spectrum showed sig-
nals at δ 9.1(br, 2H, 2NH) ppm; and the mass spectrum exhibited a
molecular ion peak [M+] at m/z = 402, which was in agreement with
its molecular weight.
In addition, the interaction of 21 with thionyl chloride gave
3-(sulfinylamino)-4H-thieno[3,4-c]benzo[h]chromen-4-one (25), which
formed via elimination of two hydrogen chloride molecules. The IR
spectrum confirmed the assigned structure, which revealed the disap-
pearance of the NH2 group bands found in the parent compound and
the presence of a (CO) group band at 1689 cm−1, and this analogy with
previous work.22,23
CONCLUSION
Enaminone 2 prepared from 1-(1-hydroxy-2-naphthyl) ethanone 1
and dimethylformamide dimethylacetal was used as a starting ma-
terial to synthesize new chromone derivatives 3, 4, 5, and 9. Active
malononitriles and hydrazines reacted with naphtho [1,2-b] pyran-
3-carbaldehyde derivative 9 through addition followed by pyran ring
opening, affording new pyridine and pyrazole derivatives 10, 11, and
12–15. Also, ethanone 1 was used as a starting material to synthesize
new chromone derivatives 16, 17, 18, and 20, and chromone deriva-
tives containing heterocyclic moiety fused onto a chromone moiety 19,
21, and 22–25.
EXPERIMENTAL
All melting points are uncorrected. Elemental analyses were carried
out in the Microanalytical Unit, National Research Center, Dokki, Giza,
Cairo. IR spectra were recorded on a Matheson 5000 FT-IR Spectrome-
ter using KBr discs. 1H-NMR spectra were recorded on a Varian Gemini
200 or a Jeol Ex-270 NMR spectrometer using TMS as an internal stan-
dard with chemical shift (δ = 0 ppm). Mass spectra were recorded on a

188
D. S. Badawy et al.
Shimazu AGC-MS QP-1000 Ex. The purities of the compounds were
checked by TLC.
Preparation of (2E)-3-Dimethylamino-1-(1-hydroxy-2-
naphthyl)prop-2-en-1-one (2)
A mixture of 1-(1-hydroxy-2-naphthyl)ethanone (1) (1.86 g, 0.01 mol)
and N, N-dimethylformamide dimethylacetal (1.78 g, 0.015 mol) in dry
toluene (25 mL) was refluxed for 3 h. After concentration, the yellow
precipitate was collected, washed with petroleum ether (bp 60–80◦C),
and recrystallized from ethanol to give 2 (90% yield) as yellow crystals,
mp 172–174◦C.
1
IR (ν/cm−1) 2950 (OH), 1643 cm−1 ( C O); H-NMR (CDCl3) δ = 3.0
(s, 3H, CH3), 3.2 (s, 3H, CH3), 5.9 (d, 1H, CH , J= 11.8 Hz), 7.5–8.0
(m, 6H, Ar-H), 8.4 (d, 1H, CH , J= 11.8 Hz) and 14.2 ppm (s, 1H, OH).
Analysis; Calcd. (%) for C15H15NO2: C 74.67; H, 6.27; N, 5.81. Found
(%): C, 74.80; H, 6.30; N, 5.80.
Synthesis of 4-Oxo-4H-naphtho[1,2-b]pyran (3)
A solution of the enaminone 2 (2.41 g, 0.01 mol) in acetic acid (25 mL)
was refluxed for 4 h. After cooling, the mixture was treated with crushed
ice and alkalified with ammonium hydroxide solution. The precipi-
tate was collected and recrystallized from ethanol to give 4-oxo-4-H-
naphtho[1,2-b]pyran 3 (91% yield) as beige crystals, mp 119–121◦C.
1
IR (ν/cm−1) = 1639 (C O), 1621 cm−1 (C C); H-NMR (DMSO-d6)
δ 6.50 (d, 1H, 2H, J= 5.9 Hz), 7.70–8.50 (m, 6H, Ar-H) and 8.10 ppm
(d, 1H, 3-H, J= 5.9 Hz). Analysis; Calcd. (%) for C13H8O2: C 79.58; H,
4.11. Found (%): C, 79.50; H, 4.00.
Synthesis of 4-Oxo-4H-naphtho[1,2-b]pyran-3-sulfinic Acid (4)
To a solution of the enaminone 2 (2.41 g, 0.01 mol) in dry benzene
(25 mL), thionyl chloride (20 mL) was added dropwise over a period
of 1 h. The precipitate was collected, washed with petroleum ether
(bp 60–80◦C), and recrystallized from ethyl acetate to give 4-oxo-4H-
naphtho[1,2-b]pyrane-3-sulfinic acid 4 (60% yield) as dark yellow crys-
tals, mp 80–82◦C.
IR (ν/cm−1) = 1639 (C O), 1620 (C C), 1364, and 1190 cm−1 (SO2);
1H-NMR (DMSO-d6) δ = 7.78–8.12 (m, 6H, Ar-H) and 8.51 ppm (s, 1H,
2-H); mass m/z 260(M+). Analysis; Calcd. (%) for C13H8O4S: C 59.99;
H, 3.10; S, 12.32. Found (%): C, 59.80; H, 3.00; S, 12.30.

Synthesis of New Derivatives Using 1-(1-Hydroxy-2-naphthyl) Ethanone
189
Synthesis of 2,3-Dibromo-4-oxo-4H-naphtho[1,2-b]pyran (5)
To a solution of the enaminone 2 (2.41 g, 0.01 mol) in dry chloroform
(25 mL), bromine (2.40 g, 0.015 mol) was added dropwise over a period of
1 h, and the mixture was heated at 40◦C for 3 h. After concentration, the
precipitate was collected and recrystallized from methanol to give 2,3-
dibromo-4-oxo-4H-naphtho[1,2-b]pyran 5 (55% yield) as yellow powder,
mp 228–230◦C.
1
IR (v/cm−1) = 1652 (C O), 1620 (C C); H-NMR (CDCl3) δ = 7.70–
8.55 ppm (m, 6H, Ar-H); mass m/z 351, 353, 355 (M+). Analysis; Calcd.
(%) for C13H6O2Br2: C, 44.11; H, 1.71; Br, 45.14. Found (%): C, 44.10;
H, 1.70; Br, 45.10.
Reaction of Enaminone 2 with p-Toluidine or p-Anisidine
A mixture of the enaminone 2 (2.41 g, 0.01 mol) and p-toluidine or p-
anisidine (0.01 mol) in absolute ethanol (20 mL) was refluxed for 3 h.
After cooling, the brown precipitates were collected and recrystallized
from ethanol to give the corresponding enaminones 6 and 7.
(2E)-3-(p-tolylamino)-1-(1-hydroxy-2-naphthyl)prop-
2-en-1-one (6)
(62% yield) mp 170–172◦C. IR (ν/cm−1) = 2950 (OH), 1649 (C O);
1H-NMR (CDCl3) δ = 2.30 (s, 3H, CH3), 6.00 (d, 1H, CH , J= 11.8 Hz),
7.10–7.80 (m, 10H, Ar-H), 8.40 (d, 1H, CH , J= 11.8 Hz), 11.80 (br d,
1H, NH) and 14.9 ppm (s, 1H, OH). Analysis; Calcd. (%) for C20H17NO2:
C 79.19; H, 5.65; N, 4.62. Found (%): C, 79.25; H, 5.70; N, 4.60.
(2E)-3-(p-anisylamino)-1-(1-hydroxy-2-naphthyl)prop-
2-en-1-one (7)
65% Yield, mp 128–129◦C. IR (ν/cm−1) = 3388 (OH), 1619 (C O); 1H-
NMR (CDCl3) δ = 3.90 (s, 3H, OCH3), 6.00 (d, 1H, CH , J= 11.8 Hz),
6.90–7.90 (m, 10H, Ar-H), 8.30 (d, 1H, CH , J= 11.8 Hz,), 11.90 (br d,
1H, NH), 15.00 ppm (s, 1H, OH). Analysis; Calcd. (%) for C20H17NO3:
C 75.22; H, 5.37; N, 4.39. Found (%): C, 75.30; H, 5.45; N, 4.40.
Synthesis of 2-Methyl-4-oxo-4H-naphtho[1,2-b]pyran-3-
carbaldehyde (9)
To a solution of the enaminone 2 (2.41 g, 0.01 mol) in dry pyridine
(10 mL) was added acetic anhydride (30 mL), and the mixture was
strirred at room temperature for 48 h. The precipitate was col-
lected, washed with petroleum ether (bp 60–80◦C), and recrystallized

190
D. S. Badawy et al.
from ethanol to give 2-methyl-4-oxo-4H-naphtho[1,2-b]pyran-3-
carbaldehyde 9 (80% yield) as colorless crystals, mp 176–178◦C.
IR (ν/cm−1) = 1687 (CHO), 1641 (C O); 1H-NMR (DMSO-d6) δ = 2.60
(s, 3H, 2-CH3), 7.80–8.50 (m, 6H, Ar-H) and 10.50 ppm (s, 1H, CHO);
mass m/z 238(M+). Analysis; Calcd. (%) for C15H10O3: C 75.62; H, 4.23.
Found (%): C, 75.60; H, 4.30.
Synthesis of 2-Amino-5-(1-hydroxy-2-naphthoyl)-4-
methylpyridine Derivatives (10, 11)
A mixture of the chromone aldehyde 9 (2.38 g, 0.01 mol) and mal-
ononitrile (0.66 g, 0.01 mol) or ethyl cyanoactate (0.23 g, 0.02 mol)
and ammonium acetate (1.0 g) in acetic acid (15 mL) was refluxed
for 4 h. After cooling, the mixture was treated with crushed ice. The
precipitates were collected and recrystallized from ethyl acetate (com-
pound from malononitrile) or ethanol (compound from ethyl cyanoac-
etate) to give the corresponding 2-amino-5-(1-hydroxy-2-naphthoyl)-4-
methylpyridine derivatives 10 and 11.
2-Amino-5-(1-hydroxy-2-naphthoyl)-4-methylpyridine-
3-carbonitrile (10)
75% Yield, yellow crystals, mp 242–243◦C; IR (ν/cm−1) = 3397–3333
(NH2), 3159 (OH), 2219 (CN), 1674 cm−1 (C O); 1H-NMR(CDCl3)
δ = 2.45 (s, 3H, 4-CH3), 5.45 (m, 2H, NH2), 7.55–7.80 (m, 6H, Ar-H)
and 8.50 ppm (s, 1H, 6-H); mass m/z 303 (M+). Analysis; Calcd. (%) for
C18H13N3O2: C 71.28; H, 4.32; N, 13.85. Found (%): C, 71.50; H, 4.21;
N, 13.80.
Ethyl 2-Amino-5-(1-hydroxy-2-naphthoyl)-4-methylpyridine-
3-carboxylate (11)
52% Yield, yellow crystals, mp 164–166◦C; IR (ν/cm−1) = 3539 (OH),
3493, 3432 (NH2), 1729 (CO2Et), 1649 (C O); 1H-NMR (CDCl3) δ = 1.45
(t, 3H, CH3 in OEt), 2.75 (s, 3H, 4-CH3), 4.50 (q,2H, in OEt), 7.70–8.10
(m,6H, Ar-H) and 8.60 ppm (s, 1H, 6-H); mass m/z 350(M+). Analysis;
Calcd. (%) for C20H18N2O4: C 68.56; H, 5.18; N, 8.00. Found (%): C,
68.25; H, 5.00; N, 8.02.
Synthesis of 4-(1-Hydroxy-2-naphthoyl)-5-methylpyrazole
Derivatives (12, 13, 14, 15)
A
mixture of chromone aldehyde
9 (2.38 g, 0.01 mol) and
hydrazine hydrate, phenylhydrazine, semicarbazide hydrochloride, or

Synthesis of New Derivatives Using 1-(1-Hydroxy-2-naphthyl) Ethanone
191
thiosemicarbazide (0.01 mol) in absolute ethanol (30 mL) was refluxed
for 3 h. After cooling, the mixture was concentrated to 10 mL. The
precipitates were collected and recrystallized from ethyl acetate (com-
pounds from hydrazines) or acetone (compounds from semicarbazides)
to give the corresponding 4-(1-hydroxy-2-naphthoyl)-5-methylpyrazole
derivatives 12, 13, 14, and 15.
4-(1-Hydroxy-2-naphthoyl)-5-methylpyrole (12)
70% Yield, yellow crystals, mp 280–282◦C; IR (ν/cm−1) = 3200, 3161
(OH, NH), 1645 (C O), 1567 (C N); 1H-NMR: (DMSO-d6) δ = 2.0 (s, 3H,
5-CH3), 7.35–8.00 (m, 7H, Ar-H and NH), 8.35 (s, 1H, 3-H), 10.65 ppm
(s, 1H, OH); mass m/z 252 (M+). Analysis; Calcd. (%) for C15H12N2O2:
C 71.42; H, 4.79; N, 11.10. Found (%): C, 71.40; H, 4.70; N, 11.10.
4-(1-Hydroxy-2-naphthoyl)-5-methyl-1-phenylpyrole (13)
65% Yield, yellow crystals, mp 228–230◦C; IR (ν/cm−1) = 3263 (OH),
1637 (C O), 1616 cm−1 (C N); 1H-NMR (DMSO-d6) δ = 2.90 (s, 3H, 5-
CH3), 6.70–8.30 (m, 11H, Ar-H), 8.55 (s, 1H, 3-H), 10.55 ppm (s, 1H,
OH). Analysis; Calcd. (%) for C21H16N2O2: C 76.81; H, 4.91; N, 8.53.
Found (%): C, 77.04; H, 5.00; N, 8.50.
4-(1-Hydroxy-2-naphthoyl)-5-methylpyrole-1-carboxamide (14)
60% Yield, yellow crystals, mp 240–241◦C; IR (ν/cm−1) = 3454 (OH),
1
3218, 3205 (NH2), 1697 (CONH2), 1637 (C O), 1624 cm−1(C N); H-
NMR (CDCl3) δ = 2.85 (s, 3H, 5-CH3), 7.7–8.25 (m,8H, Ar-H and NH2),
8.6 (s, 1H, 3-H), 10.5 ppm (s, 1H, OH). Analysis; Calcd. (%) for
C16H13N3O3: C 65.08; H, 4.44; N, 14.23. Found (%): C, 65.00; H, 4.35;
N, 14.20.
4-(1-Hydroxy-2-naphthoyl)-5-methylpyrole-
1-thiocarboxamide (15)
72% Yield, colorless crystals, mp 206–208◦C; IR (ν/cm−1) = 3425
1
(OH), 3396, 3359 (NH2), 1639 (C O), 1627 (C N); H-NMR (CDCl3)
δ = 2.90 (s, 3H, 5-CH3), 7.6–8.40 (m, 8H, Ar-H and NH2), 8.60 (s, 1H,
3-H), 11.6 ppm (s, 1H, OH). Analysis; Calcd. (%) for C16H13N3O2S: C
61.72; H, 4.21; N, 13.50, S, 10.30. Found (%): C, 61.81; H, 4.52; N, 13.51;
S, 10.32.

192
D. S. Badawy et al.
Synthesis of 2-Imino-4-methyl-2 H-benzo[h]
chromene-3-carbonitrile (16)
To a solution of 1 (1.86 g, 0.0l mol), malononitrile (2.38 g, 0.0l mol) in
(20 mL) ethanol , Na metal (0.04 g) dissolved in ethanol (10 mL) was
added dropwise. The reaction mixture was heated for 5 min, then set
aside for 2 days at room temperature. The solid which was formed fil-
tered off, dried , recrystallized from ethanol to give 2 as yellow crystals,
yield (85%), m.p. 230–232◦C.
1
IR: (ν/cm−1) = 3268, ( NH), 2225 (CN) and 1604 (C NH); H-NMR
(DMSO): δ = 2.20 (s, 3H, CH3), 7.60–8.30 (m, 6H, Ar-H) and 8.45 ppm
(s, 1H, NH); MS: m/z = 234 (M+). Analysis; Calcd (%) for C15H10N2O:
Calcd.: C, 76.91; H, 4.30; N, 11.96 Found (%): C, 76.96; H, 4.00; N, 11.95.
Synthesis of [Amino(2-imino-4-methyl-2H-benzo [h]
chromen-3-yl) methylene] Malononitrile (17)
Method A
A mixture of the imine 16 (2.34 g, 0.01 mol) and malononitrile (0.66 g,
0.01 mol) in ethanol (20 mL) was heated to dissolve, then cooled to 20◦C
and a few drops of piperidine was added. The mixture was set aside for
3 days. The solid that formed was filtered off, and recrystallized from
acetone.
Method B
A mixture of 1 (1.86 g, 0.01 mol), excess malononitrile (2.64 g,
0.04 mol), and 20 mL absolute ethanol was heated for dissolving , then
cooled to 20◦C , and a few drops of piperidine was added. The reaction
mixture was set aside for 2–3 days, then it was poured into ice water.
The solid that formed ws filtered off, and recrystallized from acetone to
give (17) as yellow crystals, yield (71%), m.p. 266–268◦C.
IR: (ν/cm−1) = 3322, 3297 (NH2,NH), 2221, 2206 (2CN) and 1654
(C NH). 1H-NMR (DMSO): δ = 2.1 (s, 3H, CH3), 7.60–8.45 (m, 6H, Ar-
H), 8.55 (s, 1H, NH), 8.96 (br s, 1H, NH) and 9.1 ppm (1H, br NH).
MS: m/z =300 (M+). Analysis; Calcd (%) for C18H14NO: C, 71.99; H,
4.03; N, 18.66. Found(%): C, 72.01; H, 4.11; N, 18.65.
Synthesis of Ethyl (2Z )-3-amino-2-cyano-3-(2-imino-4-methyl-
2H-benzo[h]chromen-3-yl) Acrylate (18)
A mixture of 16 (2.34 g, 0.0l mol), ethyl cyanoacetate (0.11 g, 0.0l mol),
in ethanol (20 mL) and a few drops of piperidine was boiled on a water
bath for 5 min. Then the reaction mixture was set aside for 2–3 days,

Synthesis of New Derivatives Using 1-(1-Hydroxy-2-naphthyl) Ethanone
193
then poured into ice water. The precipitate that formed was filtered off,
dried, and recrystallized from methanol to give 18 as yellow crystals
yield (61%), m.p. 185–186◦C.
IR: (ν/cm−1) = 3322, 3268 (NH2,NH), 2225 (CN), 1720 (C O ester)
1
and 1620 cm−1(C N). H-NMR (DMSO): δ = 1.45 (t, 3H, CH3 ester),
2.10 (s, 3H, CH3), 4.45 (q, 2H, CH2 ester), 7.50–8.50 (m, 6H, Ar-H), 8.60
(s, 1H, NH), 8.96 (br.s, 1H, NH) and 9.06 ppm (br s, 1H, NH). MS: m/z
= 347 (M+).
Analysis; Calcd (%) for C20H17N3O3: C, 69.15; H, 4.93; N, 12.10.
Found (%): C, 69.10; H, 4.90; N, 12.11.
Synthesis of 4-Imino-4H-thieno
[3,4-c]benzo[h]chromen-3-amine (19)
A suspension of 16 (2.34 g, 0.01 mol in ethanol (50 mL), elemental sulfur
(0.64 g, 0.02 mol), and a catalytic amount of morpholine was refluxed
for 3 h. The solvent was then evaporated and the remaining solid was
collected, dried, and recrystallized from ethanol and benzene (1:1) to
give 19 as dark brown crystals m.p. > 300◦C, yield (86%).
IR: (ν/cm−1) = 3321, 3278, 3195 (NH2, NH) and 1619 cm−1(C N);
1H-NMR (DMSO): δ = 6.96 (s, 1H, thiophene) and 7.1–8.55 ppm (m,
9H, Ar-H, NH and NH2). MS: m/z = 266 (M+).
Analysis; Calcd (%) for C15H10N2OS: C, 67.65; H, 3.78; N, 10.52; S,
12.04. Found (%): C, 67.60; H, 3.80; N, 10.50; S, 12.
Synthesis of 4-Methyl-2-oxo-2H-benzo[h]chromene-3-
carbonitrile (20)
Compound 20 was obtained by dissolving compound 16 (2.34 g,
0.01 mol) in ethanol (20 mL) by boiling. Then acidification was applied
by pouring it into a beaker containing 1mL conc. HCl and crushed ice.
The solid that formed was filtered off, dried, and recrystallized from
ethanol and benzene (1:1) to give 20 as yellow crystals, yield (90%),
m.p. 247–248◦C.
IR: (ν/cm−1) = 2226 (CN) and 1726cm−1(C O). 1H-NMR (DMSO):
δ = 2.8 (s, 3H, CH3) and 7.65–8.45 ppm (m, 6H, Ar-H). MS: m/z = 235
(M+). Analysis; Cacld (%) for C15H9NO2: C, 76.95; H, 3.86; N,
5.95.Found (%): C, 76.90; H, 3.82; N, 5.90.
Synthesis of 3-Amino-4H-thieno[3,4-c]benzo[h]chromen-
4-one (21)
A suspension of 20 (2.35 g, 0.01 mol) in ethanol (50 mL), elemental
sulfur (0.64 g, 0.02 mol), and a catalytic amount of morpholine was

194
D. S. Badawy et al.
refluxed for 3 h. The solvent was then evaporated, and the remaining
solid was collected, dried, and recrystallized from benzene to give 21 as
brown crystals, yield (75%), m.p. 214–216◦C.
IR: (ν/cm−1) = 3408, 3287 (NH2) and 1677 cm−1(C O). 1H-NMR
(DMSO): δ = 6.95 (s, 1H, thiophene) and 7.30–8.60 ppm (m, 8H, Ar-H,
and NH2). MS: m/z = 267 (M+). Analysis; Calcd (%) for C15H9NO2S: C,
67.40; H, 3.39; N, 5.24; S, 12.00. Found (%): C, 67.35; H, 3.34; N, 5.25;
S, 12.02.
Synthesis of N-(4-oxo-4H-thieno[3,4-c]benzo[h]chromen-3-yl)
Acetamide (22)
A solution of 16 (2.67 g, 0.0l mol) and acetic anhydride (15 mL) was
refluxed for 3 h, after being poured into ice water for cooling. The solid
that formed was filtered off, dried, and recrystallized from chloroform
to give 22 as brown powder, m.p. 248–250◦C.
IR: (ν/cm−1) = 3300 (NH) and 1680br (2C O). 1H-NMR (DMSO):
δ = 2.30 (s, 3H, CH3) 6.90 (s, 1H, thiophene) and 7.50–8.30 ppm (m, 7H,
Ar-H and NH). Analysis; Calcd (%) for C17H11NO3S: C, 66.01; H, 3.58;
N, 4.53; S, 10.37. Found (%:): C, 66.00; H, 3.54; N, 4.50; S, 10.35.
Synthesis of 3-{[(1E)-(4-chlorophenyl)methylene]amino}-4H-
thieno[3,4-c]benzo[h]chromen-4-one (23)
A solution of 21 (2.67 g, 0.0l mol) and p-chlorobenzaldehyde (1.41 g,
0.01 mol) in ethanol (30 mL) and in the presence of piperidine (0.5 mL)
was refluxed for 4 h. The solid that formed was filtered off, dried, and
recrystallized from acetone to give 23 as green powder, m.p. 230–232◦C,
yield (75%). IR: (ν/cm−1) = 1677 (C O) and 1599 (C N). MS: m/z =389.6
(M+). Analysis; Calcd for C22H12NO2S: C, 67.78; H, 3.10; N, 3.59; S, 8.23;
Cl, 9.09. Found (%:): C, 67.74; H, 3.00; N, 3.57; S, 8.20; Cl, 9.08.
Synthesis of N-(4-imino-4H-thieno[3,4-c]benzo[h]
chromen-3-yl)ethanethioamide (24)
To a solution of 21 (2.67 g, 0.01 mol) in ethanol (30 mL), phenyl isoth-
iocyanate (2.7 g, 0.02 mol) and triethyl amine (0.5 mL) were added.
The mixture was refluxed for 3 h. After cooling, the reaction mixture
was poured into ice water, and the solid that formed was filtered off,
dried, and recrystallized from ethanol to give 24 as brown crystals, m.p.
280–282◦C, yield (65%).

Synthesis of New Derivatives Using 1-(1-Hydroxy-2-naphthyl) Ethanone
195
IR: (ν/cm−1) 3297, 3160 (2NH), 1677 (C O) and 1263 (C S). 1H-
NMR (DMSO): δ = 6.95 (s, 1H, thiophene), 7.40–8.60 (m, 11H, Ar-H)
and 9.10 ppm (br, 2H, 2NH). MS: m/z = 402 (M+). Analysis; Calcd(%)
for C22H14N2O2S2: C, 65.65; H, 3.51; N, 6.96; S, 15.93. Found (%): C,
65.60; H, 3.53; N, 6.95; S, 15.90.
Synthesis of 3-Sulfinylamino)-4H-thieno[3,4-c]-
benzo[h]chromen-4-one (25)
A mixture of 21 (2.67 g, 0.0l mol) and thionyl chloride (1.78 g, 0.015
mol) in dry dioxane (30 mL) was refluxed for 5 h. Dioxane was then
evaporated, and the dark green solid that formed was recrystallized
from chloroform to give 25 m.p. 223–225◦C, yield (70%).
IR: (ν/cm−1) 1068 (S O) and 1689 (C O). 1H-NMR (DMSO): δ = 6.90
(s, 1H, thiophene) and 7.50–8.30 ppm (m, 6H, Ar-H). Analysis; Calcd for
C15H7NO3S2:C, 57.49; H, 2.25; N, 4.47; S, 20.47. Found (%): C, 57.50;
H, 2.21; N, 4.45; S, 20.45.
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