A facile route to the synthesis of new 2,3-disubstituted benzocoumarins

Article abstract of DOI:10.1080/00397910801997850

Triphenylphosphine catalyzes the reaction between 2-hydroxy-1- naphthaldehyde and π-deficient acetylenes to give the newly prepared benzo[f]chromenes. The mechanism for the formation of products is discussed. Copyright Taylor & Francis Group, LLC.

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A Facile Route to the Synthesis
of New 2,3-Disubstituted
Benzocoumarins
Kamal M. El-Shaieb a , Raafat M. Shaker a & Ashraf
A. Aly a
a Chemistry Department , Faculty of Science, El-
Minia University , El-Minia, Egypt
Published online: 13 Jun 2008.
To cite this article: Kamal M. El-Shaieb , Raafat M. Shaker & Ashraf A. Aly (2008) A
Facile Route to the Synthesis of New 2,3-Disubstituted Benzocoumarins, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 38:12, 2054-2060, DOI: 10.1080/00397910801997850
To link to this article: http://dx.doi.org/10.1080/00397910801997850
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Synthetic Communications1, 38: 2054–2060, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801997850
Facile Route to the Synthesis of New
2,3-Disubstituted Benzocoumarins
Kamal M. El-Shaieb, Raafat M. Shaker, and Ashraf A. Aly
Chemistry Department, Faculty of Science, El-Minia University,
El-Minia, Egypt
Abstract: Triphenylphosphine catalyzes the reaction between 2-hydroxy-1-
naphthaldehyde and p-deficient acetylenes to give the newly prepared benzo[ f ]-
chromenes. The mechanism for the formation of products is discussed.
Keywords: Benzo[ f ]chromenes; p-deficient acetylenes; 2-hydroxy-1-naphthaldehyde
INTRODUCTION
Organophosphanes have received special attention, and among the
phosphanes, triphenylphosphine (Ph3P) has emerged as the reagent of
choice.[1] Ph3P adds to dimethyl acetylenedicarboxylate (DMAD) to
generate a zwitterionic phosphorane derivative.[2] Addition of the zwitter-
ionic intermediate to 1,2-diketones affords spirolactone derivatives
in good yield,[3] whereas it adds to 2-hydroxybenzaldehydes to form
2H-chromene derivatives.[4] We reported that adding the zwitterionic
intermediate to 2-mercaptoperimidine and 2-mercaptobenzimidazole pro-
duced the corresponding benzo[de]anthracene, cyclopenta[a]phenalene,
and benzo[4,5]imidazo-[2,1-b]thiazole.[5] Coumarin is the structural motif
of many natural and synthetic compounds that endows them with a wide
range of biological activities. Given the development of coumarins as
photosensitizers,[6] anti-HIV agents,[7] antibiotics,[8] rodenticides, and
oral anticoagulants,[9] there is continuing interest in the synthesis of these
materials. Establishment of the synthetic procedure of 2,3-disubstituted
Received in the U.K. September 26, 2007.
Address correspondence to Ashraf A. Aly, Chemistry Department, Faculty of
Science, El-Minia University, 61519-El-Minia, Egypt. E-mail: ashraf160@yahoo.
com
2054

2,3-Disubstituted Benzocoumarins
2055
ester of coumarin derivatives will be valuable because many other hetero-
cyclic compounds can be prepared via addition and=or elimination reac-
tions on these ester groups. This work is the continuation of a program
with the aim to develop new simple methods for the synthesis of function-
ally substituted heterocycles with prospective biological and pharmaceu-
tical activities.[10–14]
RESULTS AND DISCUSSION
Compound 1 was reacted with an in situ generated 1:1 adduct of triphe-
nylphosphine and acetylenedicarboxylates 2a–d to produce in good yields
3H-benzo[ f ]chromene-2,3-dicarboxylates 3a–d (Scheme 1).
An equimolar mixture of both 1 and 2a–d in absolute benzene was
refluxed for 3–9 h in the presence of PPh3 to afford the products 3a–d
(Scheme 1). The compounds 3a–d were separated from triphenylpho-
1
sphine oxide, and their structures were deduced by IR, H NMR, 13C
NMR, and mass spectra as well as elemental analyses. The mass spectra
of compounds 3a–d displayed molecular ion peaks at m=z ¼ 298, 326, 254
1
and 390, respectively. The H NMR spectrum of 3a exhibited two single
sharp lines at d ¼ 3.84 and 3.59 ppm, characteristic for the two ester-
methyl protons; the 2H-chromene proton resonates at d ¼ 6.02 ppm,
and the H-4 proton resonates at 8.27 ppm. The other aromatic protons
resonate as four doublets and two triplets at the range d ¼ 8.19–
7.31 ppm. The 13C NMR spectrum of 3a shows seventeen distinct
resonances in agreement with the chromene structure (see Experimental
Scheme 1. Reaction of 2-hydroxy-1-naphthaldehyde (1) with acetylene deriva-
tives 2a–d; synthesis of benzo[ f ]chromenes 3a–d.

2056
K. M. El-Shaieb et al.
section). The 1H NMR and 13C NMR spectra of 3b are similar to those of
1
3a except for the ester group. The H NMR spectrum of 3c exhibited,
besides the aromatic protons in the range d ¼ 8.11–7.42 ppm, two sharp
singlets at d ¼ 8.41 and 6.91 ppm for the H-4 and 2H-chromene protons
respectively. In addition, there are a quartet and a triplet at d ¼ 4.11 and
1.10 assigned to -CH2 and -CH3 protons, respectively. The carbonyl-ester
group, which absorbed in the IR spectrum at 1705 cmꢀ1, resonated in the
13C NMR spectrum at d ¼ 172.3 ppm. Both mass spectrum and elemental
analysis reveal the molecular formula of compound 3c as C16H14O3. The
structure of the product 3d is fully supported by this analytical and spec-
troscopic data. Both mass spectrum and elemental analysis confirm the
molecular formula of product 3d as C27H18O3. Besides the signals due
to the aromatic protons in the phenyl and naphthyl moieties, its 1H
NMR spectrum contains sharp singlets at d ¼ 6.92 and 8.51 ppm,
assigned to the 2H-chromene and H-4 protons respectively.
The reaction can be rationalized on the basis of the well-known
chemistry of trivalent phosphorus nucleophiles.[15] Addition of triphenyl-
phosphine to acetylenic ester 2a–d forms the zwitter salt 1:1 adduct 4,
which upon abstraction of a proton from 1 produces 5 (Scheme 2).
=
The negatively charged oxygen attacks at the C C bond to give the
adduct 6. The reaction ultimately entails an intramolecular Wittig
reaction of the postulated phosphorane 6, which loses triphenylphos-
phine oxide to yield the products 3a–d.
In conclusion, we have found a simple and efficient route to the
synthesis of 3H-benzo[ f ]chromene-2,3-dicarboxylates 3a–d, which are
not obtained easily or as the sole products by other methods.[15] These
functionalized products are amenable to further transformations, and
we anticipate that they may have important applications in medicinal
and synthetic organic chemistry. Moreover, 2,3-diesters of coumarin
derivatives will be valuable as precursors to prepare many other
Scheme 2. Rationale formation of benzocuomarins 3a–d.

2,3-Disubstituted Benzocoumarins
2057
heterocyclic compounds via addition and=or elimination reactions on
these ortho-ester groups.
EXPERIMENTAL
All melting points were recorded on a Gallenkamp apparatus. The IR
spectra were obtained on a Shimadzu 470 spectrophotometer using pot-
1
assium bromide pellets. The H NMR (400.134 MHz) and 13C NMR
(100.6 MHz) spectra were measured in DMSO-d6 using a Bruker AM
400 spectrometer. Coupling constants are expressed in hertz. Mass spec-
tra were recorded on a Finnigan MAT 8430 instrument at 70 eV. Elemen-
tal analyses were carried out in the Microanalysis Center of Cairo
University. For preparative thin-layer chromatography (TLC), glass
plates (20 ꢁ 48 cm) were covered with a slurry of silica gel Merck PF254
and air dried using the solvents listed for development. Zones were
detected by quenching of indicator fluorescence upon exposure to
254 nm light; elution of the different bands with toluene afforded the pure
products.
Starting Materials
2-Hydroxy-1-naphthaldehyde (1) and triphenylphosphine were bought
from Merck. Compounds 2a, 2b, and 2c were bought from Fluka.
Dibenzoylacetylene (2d) was prepared according to Ref. 16. Benzene
was purified by the procedure mentioned in Ref. 17.
General Procedure
Into a 250-cm3 two-necked round-bottomed flask containing a solution
of 1 (0.172 g, 1 mmol) and triphenylphosphine (0.262 g, 1 mmol) in absol-
ute benzene (100 mL), a solution of 2a–d (1.1 mmol) in absolute benzene
(5 mL) was added dropwise with stirring. The mixture was stirred at room
temperature for 1 h and at reflux for 3–9 h (the reaction was monitored
by TLC analyses). The solvent was evaporated under vacuum, and the
formed solid products were purified by dissolving them in dry acetone
(30 mL) and then subjected to preparative plates chromatography (silica
gel), toluene–ethyl acetate (10:1). The fastest migrating zones were identi-
fied as triphenylphosphine oxide (i.e., TLC analysis), whereas the slowest
zones were identified as products 3a–d, which were recrystallized from the
stated solvents.

2058
K. M. El-Shaieb et al.
Data
Dimethyl-3H-benzo[ f ]chromene-2,3-dicarboxylate (3a)
Yellow crystals, mp ¼ 198 ꢂC (200 mg, 67%). IR (KBr): n ¼ 3070–3018
(Ar-CH), 2965–2873 (aliph-CH), 1710 (C ¼ O) cmꢀ1
.
1H NMR
(DMSO-d6): d ¼ 8.27 (s, 1H, H-4), 8.19 (d, 1H, J ¼ 8.3 Hz), 8.00 (d,
1H, J ¼ 8.9 Hz), 7.91 (d, 1H, J ¼ 7.8 Hz), 7.60 (t, 1H, J ¼ 7.1 Hz), 7.49
(t, 1H, J ¼ 7.1 Hz), 7.31 (d, 1H, J ¼ 8.9 Hz), 6.02 (s, 1H, H-2), 3.84 (s,
3H, CH3-ester), 3.59 (s, 3H, CH3-ester). 13C NMR (DMSO-d6):
d ¼ 170.8, 165.2 (2C ¼ O), 150.4 (C-O), 135.6 (C-4), 133.3, 130.5
(Ar-C), 129.7, 129.1, 128.5 126.8, 123.7, 122.6, 120.4 (Ar-CH), 114.1
(Ar-C), 80.9 (C-2), 52.3, 50.9 (2CH3). MS (EI, 70 eV), m=z ¼ 298 [Mþ ,
10], 239 [Mþ -COOCH3] (100), 196 (20), 168 (24), 151 (20), 104 (36), 76
(26). Calcd. for C17H14O5 (298.30): C, 68.45; H, 4.73. Found: C, 68.28;
H, 4.71.
Diethyl-3H-benzo[ f ]chromene-2,3-dicarboxylate (3b)
Yellow crystals, mp ¼ 210 ꢂC (232 mg, 71%). IR (KBr): n ¼ 3074–3016
(Ar-CH), 2957–2891 (aliph-CH), 1708 (C ¼ O) cmꢀ1
.
1H NMR
(DMSO-d6): d ¼ 8.32 (s, 1H, H-4), 8.21 (d, 1H, J ¼ 8.3 Hz), 8.10 (d,
1H, J ¼ 8.9 Hz), 7.94 (d, 1H, J ¼ 7.8 Hz), 7.60 (t, 1H, J ¼ 7.1 Hz), 7.49
(t, 1H, J ¼ 7.1 Hz), 7.31 (d, 1H, J ¼ 8.9 Hz), 6.15 (s, 1H, H-2), 4.31 (q,
2H, J ¼ 7.1 Hz, CH2-ester), 4.12 (q, 2H, J ¼ 7.1 Hz, CH2-ester), 1.32 (t,
3H, J ¼ 7.0 Hz, CH3-ester), 1.18 (t, 3H, J ¼ 7.1 Hz, CH3-ester). 13C
NMR (DMSO-d6): d ¼ 172.7, 166.5 (2C ¼ O), 152.1 (C-O), 134.7 (C-
4), 133.6, 131.0 (Ar-C), 129.8, 129.4, 128.5, 126.8, 123.9, 122.5, 121.3
(Ar-CH), 114.6 (Ar-C), 81.2 (C-2), 61.3, 59.8 (2CH2), 15.3, 14.6
(2CH3). MS (EI, 70 eV): m=z ¼ 326 [Mþ ] (28), 297 (14), 253 [Mþ -COOEt]
(100), 238 (28), 224 (22), 180 (42), 128 (60), 91 (32), 70 (46). Calcd. for
C19H18O5 (326.35): C, 69.93; H, 5.56. Found: C, 69.68; H, 5.48.
Ethyl-3H-benzo[ f ]chromene-3-carboxylate (3c)
Colorless crystals, mp ¼ 168 ꢂC (155 mg, 61%). IR (KBr): n ¼ 3050 (Ar-
CH), 2989 (aliph-CH), 1705 (C ¼ O) cmꢀ1
.
1H NMR (DMSO-d6):
d ¼ 8.41 (s, 1H, H-4), 8.11 (d, 1H, J ¼ 8.3 Hz), 7.90 (d, 1H, J ¼ 8.3 Hz),
Hz), 7.82 (d, 1H, J ¼ 8.3 Hz), 7.56 (t, 2H, J ¼ 7.8 Hz), 7.42 (t, 2H,
J ¼ 7.7 Hz), 6.91 (s, 1H, J ¼ 7.9 Hz, H-2), 4.11 (q, 2H, J ¼ 7.1 Hz,
CH2-ester), 1.10 (t, 3H, J ¼ 7.0 Hz, CH3-ester). 13C NMR (DMSO-d6):
d ¼ 172.3 (C ¼ O), 152.1 (C-O), 134.7, 133.6 (Ar-C), 129.8, 129.4,

2,3-Disubstituted Benzocoumarins
2059
128.5, 126.8, 123.9, 122.5, 121.7, 119.1 (Ar-CH), 114.5 (Ar-C), 82.1 (C-2),
59.2 (CH2), 15.3 (CH3). MS (EI, 70 eV): m=z ¼ 254 [Mþ , 20], 253 [Mþ -1]
(100), 225 [Mþ -CH2CH3] (40), 152 (24), 139 (28), 63 (16). Calcd. for
C16H14O3 (254.29): C, 75.58; H, 5.55. Found: C, 75.28; H, 5.45.
(3H-Benzo[ f ]chromene-2,3-diyl)bis(phenylmethanone) (3d)
Yellow crystals, mp ¼ 277 ꢂC (230 mg, 59%). IR (KBr): n ¼ 3068–3011
1
(Ar-CH), 2897 (aliph-CH), 1669 (C ¼ O) cmꢀ1. H NMR (DMSO-d6):
d ¼ 8.51 (s, 1H, H-4), 8.21 (d, 1H, J ¼ 8.3 Hz), 8.15 (d, 1H, J ¼ 8.9 Hz),
8.08, 7.94 (d, 1H, J ¼ 7.8 Hz), 7.86 (t, 1H, J ¼ 7.1 Hz), 7.69 (t, 1H,
J ¼ 7.1 Hz), 7.61 (d, 1H, J ¼ 8.9 Hz), 7.56–7.50 (m, 4H), 7.41–7.36 (m,
4H), 7.32–7.27 (m, 2H), 6.92 (s, 1H, H-2). 13C NMR (DMSO-d6):
d ¼ 192.8, 187.2 (2C ¼ O), 151.0 (C-O), 139.5 137.3 (Ar-C), 136.7 (C-
4), 134.4, 133.1, 130.5 (Ar-C), 129.7, 129.1, 128.5, 128.2, 126.8, 123.7,
122.6, 120.0 (Ar-CH), 115.3 (Ar-C), 84.9 (C-2); MS (EI, 70 eV):
m=z ¼ 390 [Mþ ] (100), 285 [Mþ -PhCO] (60), 208 (22), 180 (68), 154
(24), 126 (40), 105 (16), 91 (20), 77 (52). Calcd. for C27H18O3 (390.44):
C, 83.06; H, 4.65. Found: C, 82.81; H, 4.53.
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