DABCO-catalyzed efficient synthesis of naphthopyran derivatives via one-pot three-component condensation reaction at room temperature

Article abstract of DOI:10.1080/00397910701862865

Diazabicyclo[2.2.2]octane (DABCO) has been used as a mild and efficient catalyst for synthesis of 2-amino-3-cyano naphthopyran derivatives via a one-pot three-component reaction of aromatic aldehydes, naphthols, and malononitrile at room temperature. The

Full text of DOI:10.1080/00397910701862865

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DABCO‐Catalyzed Efficient Synthesis of
Naphthopyran Derivatives via One‐Pot
Three‐Component Condensation Reaction at
Room Temperature
Saeed Balalaie a , Sorour Ramezanpour a , Morteza Bararjanian a & Jürgen H.
Gross b
a Peptide Chemistry Research Group, K. N. Toosi University of Technology,
Tehran, Iran
b Institute of Organic Chemistry, University of Heidelberg, Heidelberg,
Germany
Published online: 12 Mar 2008.
To cite this article: Saeed Balalaie , Sorour Ramezanpour , Morteza Bararjanian & Jrgen H. Gross (2008)
DABCO‐Catalyzed Efficient Synthesis of Naphthopyran Derivatives via One‐Pot Three‐Component Condensation
Reaction at Room Temperature, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 38:7, 1078-1089, DOI: 10.1080/00397910701862865
To link to this article: http://dx.doi.org/10.1080/00397910701862865
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Synthetic Communicationsw, 38: 1078–1089, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701862865
DABCO-Catalyzed Efficient Synthesis
of Naphthopyran Derivatives via One-Pot
Three-Component Condensation Reaction
at Room Temperature
Saeed Balalaie,1 Sorour Ramezanpour,1
Morteza Bararjanian,1 and Ju¨rgen H. Gross2
1Peptide Chemistry Research Group, K. N. Toosi University of
Technology, Tehran, Iran
2Institute of Organic Chemistry, University of Heidelberg, Heidelberg,
Germany
Abstract: Diazabicyclo[2.2.2]octane (DABCO) has been used as a mild and efficient
catalyst for synthesis of 2-amino-3-cyano naphthopyran derivatives via a one-pot three-
component reaction of aromatic aldehydes, naphthols, and malononitrile at room temp-
erature. The short reaction times, easy workup, good to excellent yields, and mild
reaction conditions make this domino Knoevenagel–Michael reaction both practical
and attractive.
Keywords: 2-Amino-chromene, DABCO, domino Knoevenagel–Michael addition,
one-pot three-component reaction, organocatalysis, naphthopyrans
INTRODUCTION
The rapid assembly of diverse molecular compounds is an important goal of
synthetic organic chemistry and is one of the key paradigms of modern
drug discovery.[1] One approach to address the challenge involves the devel-
opment of atom-economical, single-pot, multicomponent coupling reactions
and multicomponent processes. These processes additionally benefit from
Received in the U. K. May 3, 2007
Address correspondence to Saeed Balalaie, Peptide Chemistry Research Group,
K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran. E-mail:
balalaie@kntu.ac.ir
1078

Synthesis of Naphthopyran Derivatives
1079
technically simple protocols, the use of common laboratory equipment, time
and energy savings, and environmental advantages and have been of particular
interest to both academic and industrial scientists.[2] When finding efficient
new catalysts, mild reaction conditions are of particular interest. An
example of such a reaction is the three-component synthesis of benzopyran
derivatives.[3] Polyfunctionalized benzo[b]pyrans and their derivatives are
important classes of oxygenated heterocycles, which have attracted much
interest because of the biological activities of naturally occurring representa-
tives.[4] Some of the reported biological activities of benzopyrans are anticoa-
gulant, spasmolytic, diuretic, anti-anaphylactin, anticancer, and antidiabetic
activities.[5] 4H-Benzo[b]pyrans and their derivatives are of considerable
interest because of their wide range of biological activities as listed.[6] In
addition, they can be used as cognitive enhancers for the treatment of neuro-
degenerative disease, including Alzheimer’s disease, amyotrophic lateral
sclerosis, Huntington’s diseases, Parkinson’s disease, AIDS-associated
dementia, and Down syndrome as well as for the treatment of schizophrenia
and myoclonus.[7] 4H-Pyrans also constitute the structural unit of a series of
natural products.[8] A number of 2-amino-4H-pyrans are useful as photoactive
materials.[9] Various methods for preparing these compounds have been
reported.[10] Recently, tetra-n-butyl ammonium bromide was used as the
catalyst for a three-component condensation to synthesize benzo[b]pyran
derivatives in water at reflux condition.[11] Each of the methods mentioned
has its own merit, with at least one of the limitations of low yield, long
reaction times, effluent pollution, harsh reaction conditions, and tedious
workup procedures. The development of an efficient, one-pot, chemoselective
procedure is therefore of considerable interest. DABCO has been used
recently as the most common catalyst in organic synthesis, for example, in
the Baillys–Hillman reaction[12] and the selective cleavage of esters.[13]
One of the remarkable features of DABCO is its efficient activity under
neat conditions or high-concentration conditions. Thus, we considered
DABCO to be an ideal base for effecting one-pot synthesis of naphthopyran
derivatives. As a part of our work on one-pot multicomponent reactions
(MCRs) for the synthesis of various heterocyclic compounds,[14] we
describe herein the DABCO-mediated three-componenet coupling of
naphthols, aromatic aldehydes and malononitrile in ethanol at room tempera-
ture to afford 2-amino-3-cyano-naphth[b]pyran derivatives in good to
excellent yields (Scheme 1).
Scheme 1.

1080
S. Balalaie et al.
RESULTS AND DISCUSSION
DABCO is one of the most commonly used catalysts in organic synthesis.
Thus, we considered this base to be ideal as a catalyst for three-component
coupling of naphthols, aromatic aldehydes, and malononitrile in ethanol at
room temperature to afford 2-amino-3-cyano-naphthopyrane derivatives
(4a–s). (see Scheme 1 and Table 1). The reaction of malononitrile,
1-naphthol, and 3-nitrobenzaldehyde was investigated in the presence of
0.1, 0.2, 0.3, and 0.5 equivalents of DABCO as catalyst. In all cases, the
reaction times were 6 h, and the product was 4p with 50, 75, 98, and 98%
yields. Optimization of the reaction components afforded reasonable yields
of 4. The best yield was obtained with 0.3 equivalent of DABCO as catalyst.
The reaction proceeded rapidly with the same yields when the amount of
DABCO was increased from 0.3 equiv. to 1.0 equiv. for 6 h under similar con-
ditions. Reactions were studied at 50 8C, but it was shown that the progress is
Table 1. DABCO-catalyzed synthesis of naphthopyrans
(4a–s) at room temperature
Entry
Naphthol
Ar
Yield (%)a
4a
4b
4c
4d
4e
4f
1-Naphthol
1-Naphthol
1-Naphthol
2-Naphthol
1-Naphthol
2-Naphthol
1-Naphthol
2-Naphthol
1-Naphthol
2-Naphthol
1-Naphthol
1-Naphthol
2-Naphthol
1-Naphthol
C6H5
75
99
95
80
82
72
87
77
85
47
75
85
91
75
4-Br-C6H4
3-Cl-C6H4
3-Cl-C6H4
4-Cl-C6H4
4-Cl-C6H4
4-CN-C6H4
4-CN-C6H4
2,3-Cl2-C6H3
2,3-Cl2-C6H3
2,4-Cl2-C6H3
3-OH-C6H4
3-OH-C6H4
3-OH-4-
4g
4h
4i
4j
4k
4l
4m
4n
OMe-C6H3
2-NO2-C6H4
3-NO2-C6H4
3-NO2-C6H4
4-CF3-C6H4
4-CF3-C6H4
4o
4p
4q
4r
4s
1-Naphthol
1-Naphthol
2-Naphthol
1-Naphthol
2-Naphthol
71
98
76
91
77
Notes. In all cases, the optimized amount of DABCO is
30% mol. Reaction conditions: Stirred at room temperature
for 2–4 h.
aYields refer to those of pure isolated products character-
1
ized by IR, H NMR, and 13C NMR spectroscopic data.

Synthesis of Naphthopyran Derivatives
1081
not sufficient, and unreacted alkene was recovered. The reactions of aldehydes
containing electron-donating groups show only a slightly slower reaction rate
and lower yields than those containing electron-withdrawing groups. The
three-component reaction of a- and b-naphthols, malononitrile, and benzal-
dehyde derivatives was carried out by using catalytic amounts of triethylamine
(0.3 equivalent), but the reaction proceeded slowly, and the only products were
the alkenes. We observed reduced chemical yields for both ortho-substituted
benzaldehyde derivatives regardless of the electronic nature of the substituent.
This suggests that steric factors for ortho-substituted alkene intermediates can
significantly reduce the reaction yield. When the three-component conden-
sations of phenol, 4-chlorophenol, or 4-nitro phenol with anisaldehyde and
malononitrile in the presence of 0.3 equiv. of DABCO was carried out, only
the alkene from the reaction of anisaldehyde and malononitrile was
produced. The same reaction conditions were employed with different
phenols without success. This reaction goes well only with naphthols.
The structures of all products were determined on the basis of their
1
analytical data. The H NMR spectra of products (4a–s) show characteristic
peaks at d 4.90–5.90 ppm for H-4. The 13C NMR spectra of 4a–s exhibit a
specific peak in the region of d 54–60 ppm that is related to C-4.
Although we have not yet established the mechanism of the one-pot
reaction of naphthols, benzaldehyde derivatives, and malononitrile in the
presence of DABCO in an experimental manner, a possible explanation is
proposed in Scheme 2. Based on this proposed mechanism, DABCO is an
effective catalyst for the formation of the olefin 6. This is readily prepared
in situ by Knoevenagel condensation of aryl aldehyde and the active
methylene compound 3, which proceeds via the intermediate 5. After dehy-
dration, the olefin 6 is produced. (Scheme 2).
DABCO also catalyzes the generation of the naphtholate anion, which
reacts with the dicyanoolefin 6, followed by cyclization to give the iminium
ion. Upon hydrolysis of this ion, the product 4 can be formed. Existence of
DABCO is essential for both steps.
In summary, we have demonstrated a rapid and efficient DABCO-
catalyzed one-pot, three-component synthesis of naphthopyran derivatives
at room temperature. The direct use of commercially available and inexpen-
sive reagents, easy workup, short reaction times, and mild reaction conditions
at room temperature make this domino Knoevenagel–Michael reaction very
attractive and practical.
EXPERIMENTAL SECTION
Melting points were determined with Electrothermal 9100 apparatus and were
uncorrected. IR spectra were obtained on an ABB FT-IR (FTLA 2000) spec-
trometer. 1H and 13C NMR spectra were run on a Bruker DRX-300 instrument
at 300 MHz and 75 MHz using TMS as internal standard and DMSO-d6,

1082
S. Balalaie et al.
Scheme 2. Proposed mechanism for the synthesis of naphthopyranes 4a–s catalyzed
by DABCO (30%).

Synthesis of Naphthopyran Derivatives
1083
CDCl3, or acetone-d6 as solvent. Mass spectra were recorded on Jeol JMS-700
(HR-EI) and Bruker APEX QE (ESI) spectrometers.
General Procedure for the Preparation of Naphthopyrans (4a–s)
A mixture of an aromatic aldehyde (1 mmol), molononitrile (79 mg,
1.1 mmol), naphthol (172 mg, 1.2 mmol), and DABCO (30 mol%) in
ethanol (5 mL) was stirred at room temperature for 2–4 h. The progress of
the reaction was monitored by thin-layer chromatography (TLC). After com-
pletion of the reaction, the mixture was then concentrated under reduced
pressure, and 0.5 ml of water was added. The remaining solid was collected
by filtration. Further purification was done by recrystallization in EtOH.
Selected Data for Compounds 4a–s
Compound 4a: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-phenyl,
mp ¼ 215–217 8C [lit. 210 8C].[11] IR (KBr, cm21) 3447, 3301, 3187,
1
2201, 1657, 1600. H NMR (300 MHz, acetone-d6, ppm): d 4.93 (s, 1H,
H-4), 6.46 (brs, 2H, NH2), 7.14 (d, 1H, J ¼ 8.3 Hz, H-Ar), 7.21–7.37
(m, 5H, H-Ar), 7.54–7.64 (m, 3H, H-Ar), 7.89 (d, 1H, J ¼ 8.3 Hz, H-Ar),
8.3 (d, 1H, J ¼ 8.3 Hz, H-Ar). 13C NMR (75 MHz, acetone-d6, ppm) d
58.75, 118.0, 119.33, 120.85, 123.38, 124.11, 126.33, 126.58, 126.70,
127.01, 127.70, 127.95, 128.67, 133.33, 143.27, 145.74, 160.04. MS (70 eV,
EI): C20H14N2O: 298 (45%, Mþ†), 222 (41%, [M-C6H4]þ†), 221 (100%,
[M-C6H5]þ).
Compound 4b: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(4-bro-
mophenyl), mp ¼ 241–243 8C (dec.). IR (KBr, cm21) 3417, 3326, 3071,
1
2195, 1625, 1593; H NMR (300 MHz, acetone-d6, ppm): d 4.97 (s, 1H,
H-4), 6.51 (brs, 2H, NH2), 7.15 (d, 1H, J ¼ 8.4 Hz, H-Ar), 7.30 (d, 2H,
J ¼ 8.3 Hz, H-Ar), 7.53 (d, 2H, J ¼ 8.3 Hz, H-Ar), 7.58–7.65 (m, 3H,
H-Ar), 7.90 (d, 1H, J ¼ 8.5 Hz, H-Ar), 8.30 (d, 1H, J ¼ 7.9 Hz, H-Ar). 13C
NMR (75 MHz, acetone-d6, ppm) d 58.2, 117.35, 119.13, 120.43, 120.87,
123.36, 124.27, 126.15, 126.66, 126.83, 127.72, 130.08, 131.70, 133.42,
143.31, 145.13, 160.07. HR-MS (70 eV, EI): C20H13N2O79Br: [M]þ found
.
376.0211; calc. 376.0212; C20H13N2O81Br [M þ 2]þ† found 378.0205; calc.
378.0219.
Compound 4c: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(3-chloro-
phenyl), mp ¼ 218–222 8C (dec.). IR (KBr, cm21) 3455, 3340, 2192, 1659,
1
1590. H NMR (300 MHz, acetone-d6, ppm): d 5.00 (s, 1H, H-4), 6.54 (brs,
2H, NH2), 7.17 (d, 1H, J ¼ 8.3 Hz, H-Ar), 7.30 (d, 2H, J ¼ 8.3 Hz, H-Ar),
7.27–7.40 (m, 4H, H-Ar), 7.56–7.65 (m, 3H, H-Ar), 7.90 (d, 1H,
J ¼ 8.5 Hz, H-Ar), 8.31 (d, 1H, J ¼ 7.8 Hz, H-Ar). 13C NMR (75 MHz,

1084
S. Balalaie et al.
acetone-d6, ppm) d 58.10, 117.21, 119.14, 120.90, 123.37, 124.33, 126.10,
126.60, 126.69, 126.87, 127.15, 127.73, 127.87, 130.43, 133.45, 134.04,
143.36, 148.15, 160.20. HR-MS (70 eV, EI): C20H13N2O35Cl [M]þ† found:
332.0705; calc. 332.0716; C20H13N2O37Cl [Mþ þ 2]þ† found: 334.0695;
calc. 334.0703.
Compound 4d: 1H-Naphtho[2,1-b]pyran-2-carbonitrile,3-amino-1-(3-chlor-
ophenyl), mp ¼ 235–238 8C (dec.). IR (KBr, cm21) 3431, 3328, 2182,
1
1646, 1588. H NMR (300 MHz, acetone-d6, ppm): d 5.40 (s, 1H, H-4),
6.34 (brs, 2H, NH2), 7.23–7.38 (m, 5H, H-Ar), 7.44–7.48 (m, 2H, H-Ar),
7.87–7.98 (m, 2H, H-Ar). 13C NMR (75 MHz, acetone-d6, ppm) d 59.08,
111.50, 115.09, 118.33, 119.49, 120.66, 120.86, 123.38, 123.93, 126.44,
126.48, 126.59, 127.67, 133.27, 137.20, 143.06, 145.77, 147.60, 159.89.
HR-MS (70 eV, EI): C20H13N2O35Cl [M]þ† found: 332.0705; calc.
332.0716; C20H13N2O37Cl [M þ 2]þ† found: 334.0695; calc. 334.0703.
Compound 4e: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(4-chloro-
)
phenyl): mp ¼ 245–248 8C [lit. 231–232 8C][11] (dec.). IR (KBr, cm21
1
3451, 3338, 2192, 1664, 1588. H NMR (300 MHz, acetone-d6, ppm): d
4.95 (s, 1H, H-4), 7.10 (d, 1H, J ¼ 8.2 Hz, H-Ar), 7.20 (brs, 2H, NH2), 7.27
(d, 2H, J ¼ 7.0 Hz, H-Ar), 7.38 (d, 2H, J ¼ 7.0 Hz, H-Ar), 7.54–7.66
(m, 3H, H-Ar), 7.88 (d, 1H, J ¼ 7.7 Hz, H-Ar), 8.22 (d, 1H, J ¼ 8.2 Hz,
H-Ar). 13C NMR (75 MHz, acetone-d6, ppm) d 56.31, 117.84, 120.86,
121.18, 123.20, 124.46, 126.52, 127.18, 127.32, 128.14, 129.15, 130.03,
132.02, 133.21, 143.22, 145.11, 160.63. HR-MS (70 eV, EI):
C20H13N2O35Cl [M]þ† found: 332.0705; calc. 332.0716; C20H13N2O37Cl
[M þ 2]þ† found: 334.0695; calc. 334.0703.
Compound 4f: 1H-Naphtho[2,1-b]pyran-2-carbonitrile,3-amino-1-(4-chloro-
)
phenyl), mp ¼ 217–220 8C [lit. 206–208 8C][11] (dec.). IR (KBr, cm21
1
3409, 3322, 3029, 2223, 1630, 1586. H NMR (300 MHz, CDCl3, ppm): d
5.36 (s, 1H, H-4), 7.11 (brs, 2H, NH2), 7.25 (d, 1H, J ¼ 8.4 Hz, H-Ar), 7.29
(d, 1H, J ¼ 8.4 Hz, H-Ar), 7.35 (d, 1H, J ¼ 8.9 Hz, H-Ar), 7.38–7.45
(m, 3H, H-Ar), 7.80 (d, 1H, J ¼ 8.2 Hz, H-Ar), 7.88 (d, 1H, J ¼ 7.8 Hz,
H-Ar), 7.92 (d, 1H, J ¼ 9.0 Hz, H-Ar). 13C NMR (75 MHz, CDCl3, ppm) d
61.18, 112.37, 113.48, 114.40, 116.68, 123.58, 125.28, 127.40, 128.56,
128.63, 129.13, 129.27, 129.92, 130.08, 131.43, 131.86, 147.10, 158.34,
158.68. HR-MS (70 eV, EI): C20H13N2O35Cl [M]þ† found: 332.0705; calc.
332.0716; C20H13N2O37Cl [M þ 2]þ†, found: 334.0695; calc. 334.0703.
Compound 4g: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(4-cyano-
phenyl), mp ¼ 258–260 8C (dec.). IR (KBr, cm21) 3436, 3325, 3053, 2230,
1
2190, 1655, 1630. H NMR (300 MHz, acetone-d6, ppm): d 5.10 (s, 1H,
H-4), 6.60 (brs, 2H, NH2), 7.15 (d, 1H, J ¼ 8.5 Hz, H-Ar), 7.56 (d, 2H,
J ¼ 8.3 Hz, H-Ar), 7.59–7.67 (m, 3H, H-Ar), 7.77 (d, 2H, J ¼ 8.3 Hz,
H-Ar), 7.90 (d, 1H, J ¼ 7.9 Hz, H-Ar), 8.31 (d, 1H, J ¼ 7.8 Hz, H-Ar). 13C
NMR (75 MHz, acetone-d6, ppm) d 58.49, 111.75, 117.63, 119.24, 119.91,

Synthesis of Naphthopyran Derivatives
1085
121.80, 124.26, 125.35, 126.88, 127.66, 127.88, 128.65, 129.94, 133.54,
134.42, 144.37, 151.81, 161.20. HR-MS (70 eV, EI): C21H13N3O: [M]þ†
found 323.1058; calc. 323.1058.
Compound 4h: 1H-Naphtho[2,1-b]pyran-2-carbonitrile,3-amino-1-(4-cyano-
phenyl), mp ¼ 285–287 8C (dec.). IR (KBr, cm21) 3440, 3301, 2223, 2182,
1
1653, 1591. H NMR (300 MHz, acetone-d6, ppm): d 5.49 (s, 1H, H-4),
6.41 (brs, 2H, NH2), 7.37 (d, 1H, J ¼ 8.9 Hz, H-Ar), 7.44–7.49 (m, 2H,
H-Ar), 7.48 (d, 2H, J ¼ 8.9 Hz, H-Ar), 7.70 (d, 2H, J ¼ 7.5 Hz, H-Ar),
7.82–7.85 (m, 1H, H-Ar), 7.92–7.95 (m, 1H, H-Ar), 7.98 (d, 1H,
J ¼ 8.9 Hz, H-Ar). 13C NMR (75 MHz, acetone-d6, ppm) d 58.93, 110.55,
114.49, 116.83, 118.28, 119.00, 123.51, 125.18, 127.30, 128.26, 128.66,
130.08, 130.55, 131.49, 132.66, 147.44, 150.73, 159.84. HR-MS (70 eV,
EI): C21H13N3O: [M]þ† found 323.1058; calc. 323.1058.
Compound 4i: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(2,3-
dichlorophenyl), mp ¼ 260–263 8C (dec.). IR (KBr, cm21) 3424, 3316,
1
2187, 1658, 1620. H NMR (300 MHz, DMSO-d6, ppm): d 5.50 (s, 1H,
H-4), 6.99 (d, 1H, J ¼ 8.5 Hz, H-Ar), 7.27 (brs, 2H, NH2), 7.23–7.35
(m, 2H, H-Ar), 7.53–7.67 (m, 4H, H-Ar), 7.84 (d, 1H, J ¼ 8.0 Hz, H-Ar),
8.24 (d, 1H, J ¼ 8.0 Hz, H-Ar). 13C NMR (75 MHz, acetone-d6, ppm) d
54.47, 116.04, 120.07, 120.77, 122.65, 124.19, 125.26, 126.80, 126.98,
127.70, 129.42, 129.95, 130.20, 132.31, 132.92, 143.07, 144.76, 160.44.
HR-MS (70 eV, EI): C20H12N2O35Cl2 [M]þ† found 366.0319; calc.
366.0327; C20H12N2O35Cl37Cl [M þ 2]þ† found 368.0282; calc. 368.0297;
C20H12N2O37Cl2 [M þ 4]þ† found 370.0261; calc. 370.0267.
Compound 4j: 1H-Naphtho[2,1-b]pyran-2-carbonitrile,3-amino-1-(2,3-
dichlorophenyl), mp ¼ 319–322 8C (dec.). IR (KBr, cm21) 3439, 3322,
1
2135, 1630, 1589. H NMR (300 MHz, acetone-d6, ppm): d 5.94 (s, 1H,
H-4), 6.38 (brs, 2H, NH2), 7.03 (d, 1H, J ¼ 7.8 Hz, H-Ar), 7.21 (t, 1H,
J ¼ 7.8 Hz, H-Ar), 7.35 (d, 1H, J ¼ 8.9 Hz, H-Ar), 7.41–7.54 (m, 3H,
H-Ar), 7.70 (d, 1H, J ¼ 8.3 Hz, H-Ar), 7.94 (d, 1H, J ¼ 7.9 Hz, H-Ar), 7.98
(d, 1H, J ¼ 9.0 Hz, H-Ar). HR-MS (70 eV, EI): C20H12N2O35Cl2 [M]þ†
found 366.0319; calc. 366.0327; C20H12N2O35Cl2 [M]þ† found 366.0319;
calc. 366.0327; C20H12N2O35Cl37Cl [M þ 2]þ† found 368.0282; calc.
368.0297; C20H12N2O37Cl2 [M þ 4]þ† found 370.0261; calc. 370.0267.
Compound 4k: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(2,4-
dichlorophenyl), mp ¼ 214–216 8C [lit. 213–215 8C][11] (dec.). IR (KBr,
cm21) 3455, 3332, 2188, 1667, 1604. 1H NMR (300 MHz, DMSO-d6,
ppm): d 5.40 (s, 1H, H-4), 6.98 (d, 1H, J ¼ 8.0 Hz, H-Ar), 7.26 (brs, 2H,
NH2), 7.36–7.39 (m, 1H, H-Ar), 7.57–7.63 (m, 4H, H-Ar), 7.88 (d, 1H,
J ¼ 6.2 Hz, H-Ar), 8.23 (d, 1H, J ¼ 6.7 Hz, H-Ar). 13C NMR (75 MHz,
acetone-d6, ppm) d 56.85, 116.37, 118.84, 120.89, 123.27, 124.44, 125.45,
126.73, 126.9, 127.73, 128.08, 129.22, 132.64, 133.08, 133.47, 133.54,
141.55, 143.53, 160.46. HR-MS (70 eV, EI): C20H12N2O35Cl2 [M]þ† found

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S. Balalaie et al.
366.0319; calc. 366.0327; C20H12N2O35Cl37Cl [M þ 2]þ† found 368.0282;
calc. 368.0297; C20H12N2O37Cl2 [M þ 4]þ† found 370.0261; calc. 370.0267.
Compound 4l: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(3-hydro-
xyphenyl), mp ¼ 250–253 8C (dec.). IR (KBr, cm21) 3445, 3337, 2182,
1
1658, 1610. H NMR (300 MHz, acetone-d6, ppm): d 5.40 (s, 1H, H-4),
6.44 (brs, 2H, NH2), 6.70–6.76 (m, 2H, H-Ar), 6.82 (d, 1H, J ¼ 7.7 Hz,
H-Ar), 7.16 (t, 2H, J ¼ 8.5 Hz, H-Ar), 7.54–7.65 (m, 3H, H-Ar), 7.88
(d, 1H, J ¼ 8.0 Hz, H-Ar), 8.29 (d, 1H, J ¼ 8.0 Hz, H-Ar). 8.33 (brs, 1H,
OH). 13C NMR (75 MHz, acetone-d6, ppm) d 58.80, 114.13, 114.79,
118.05, 119.07, 119.43, 120.82, 123.36, 124.08, 126.34, 126.56, 126.67,
127.70, 129.67, 133.33, 143.25, 147.30, 157.79, 160.06. ESI: C20H15N2O2
[M þ 1]þ found 315.11280; calc. 314.1129, C20H14N2O2Na [M þ Na]þ
found 337.09475; calc. 337.09493, C40H28N4O4Na [2M þ Na] found
651.20028; calc. 651.20047.
Compound 4m: 1H-Naphtho[2,1-b]pyran-2-carbonitrile,3-amino-1-(3-
hydroxyphenyl), mp ¼ 280–282 8C (dec.). IR (KBr, cm21) 3419, 3327,
1
2187, 1642, 1586. H NMR (300 MHz, acetone-d6, ppm): d 5.40 (s, 1H,
H-4), 6.23 (brs, 2H, NH2), 6.63–6.67 (m, 2H, H-Ar), 6.77 (d, 1H,
J ¼ 7.6 Hz, H-Ar), 7.10 (t, 1H, J ¼ 7.6 Hz, H-Ar), 7.34 (d, 1H, J ¼ 8.9 Hz,
H-Ar), 7.40–7.49 (m, 2H, H-Ar), 7.92 (t, 3H, J ¼ 8.9 Hz, H-Ar), 8.35 (brs,
1H, OH). 13C NMR (75 MHz, acetone-d6, ppm) d 60.18, 113.82, 114.10,
115.81, 116.73, 118.36, 119.44, 123.84, 124.96, 126.99, 128.46, 129.47,
129.65, 130.89, 131.43, 147.12, 147.30, 157.78, 159.60. ESI: C20H15N2O2
[M þ 1]þ found 315.11280; calc. 314.1129; C20H14N2O2Na [M þ Na]þ
found 337.09475; calc. 337.09493; C40H28N4O4Na [2M þ Na]þ found
651.20028; calc. 651.20047.
Compound
4n:
4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(3-
)
hydroxy-4-methoxyphenyl), mp ¼ 174–177 8C (dec.). IR (KBr, cm21
1
3337, 3195, 2193, 1665, 1610. H NMR (300 MHz, acetone-d6, ppm): d
3.80 (s, 3H, OMe), 4.85 (s, 1H, H-4), 6.39 (brs, 2H, NH2), 6.76–6.81
(m, 2H, H-Ar), 6.96 (d, 1H, J ¼ 1.50 Hz, H-Ar), 7.18 (d, 1H, J ¼ 8.5 Hz,
H-Ar), 7.55–7.61 (m, 3H, H-Ar), 7.87 (d, 1H, J ¼ 7.8 Hz, H-Ar), 8.28
(d, 1H, J ¼ 7.8 Hz, H-Ar). 13C NMR (75 MHz, acetone-d6, ppm) d 55.38,
59.05, 111.49, 115.08, 118.33, 119.50, 120.65, 123.38, 123.93, 126.45,
126.48, 126.59, 127.67, 133.27, 137.20, 143.05, 145.76, 147.59, 159.89.
HR-MS (70 eV, EI): C11H8N2O2 [M-C10H6-H2O]þ found 200.0588; calc.
200.0586.
Compound 4o: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(2-nitro-
phenyl), mp ¼ 241–242 8C (dec.). IR (KBr, cm21) 3471, 3332, 2192, 1663,
1610, 1596, 1550, 1374. 1H NMR (300 MHz, DMSO-d6, ppm): d 5.45
(s, 1H, H-4), 7.06 (d, 1H, J ¼ 8.5 Hz, H-Ar), 7.29 (brs, 2H, NH2), 7.36
(d, 1H, J ¼ 7.8 Hz, H-Ar), 7.49 (t, 1H, J ¼ 7.6 Hz, H-Ar), 7.60–7.69
(m, 4H, H-Ar), 7.90 (d, 2H, J ¼ 7.2 Hz, H-Ar), 8.50 (d, 1H, J ¼ 8.0 Hz,

Synthesis of Naphthopyran Derivatives
1087
H-Ar). 13C NMR (75 MHz, acetone-d6, ppm) d 55.70, 116.58, 120.39, 121.27,
123.15, 124.34, 124.73, 126.03, 127.32, 127.55, 128.17, 128.96, 132.32,
133.40, 134.08, 139.17, 143.58, 149.28, 160.69. HR-MS (70 eV, EI):
C20H13N3O3 [M]þ† found 343.0977; calc. 343.0957.
Compound 4p: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(3-nitro-
phenyl), mp ¼ 217–1219 8C (dec.). [lit. 214–216 8C].[11] IR (KBr, cm21
)
3460, 3363, 2183, 1650, 1603, 1596. 1H NMR (300 MHz, acetone-d6,
ppm): d 5.22 (s, 1H, H-4), 6.65 (brs, 2H, NH2), 7.20 (d, 1H, J ¼ 8.5 Hz,
H-Ar), 7.58–7.70 (m, 4H, H-Ar), 7.82 (d, 1H, J ¼ 7.7 Hz, H-Ar), 7.91
(d, 1H, J ¼ 7.7 Hz, H-Ar), 8.15 (d, 1H, J ¼ 8.5 Hz, H-Ar), 8.33 (d, 1H,
J ¼ 8.5 Hz, H-Ar). 13C NMR (75 MHz, acetone-d6, ppm) d 57.68, 116.72,
119.03, 120.94, 122.11, 122.48, 123.37, 124.52, 125.98, 126.80, 127.02,
127.76, 130.20, 133.54, 134.52, 143.47, 147.95, 148.63, 160.35. HR-MS
(70 eV, EI): C20H13N3O3 [M]þ† found 343.0977; calc. 343.0957.
Compound 4q: 1H-Naphtho[2,1-b]pyran-2-carbonitrile,3-amino-1-(3-nitro-
phenyl), mp ¼ 239–241 8C (dec.). IR (KBr, cm21) 3464, 3357, 2192, 1657,
1
1590. H NMR (300 MHz, DMSO-d6, ppm): d 5.61 (s, 1H, H-4), 7.15 (brs,
2H, NH2), 7.38 (d, 1H, J ¼ 8.9 Hz, H-Ar), 7.42–7.48 (m, 2H, H-Ar), 7.57
(t, 1H, J ¼ 7.8 Hz, H-Ar), 7.65 (m, 1H, H-Ar), 7.85 (d, 1H, J ¼ 7.5 Hz,
H-Ar), 7.91–7.96 (m, 2H, H-Ar), 8.00 (d, 1H, J ¼ 6.3 Hz, H-Ar), 8.05
(m, 1H, H-Ar). 13C NMR (75 MHz, DMSO-d6, ppm) d 57.42, 115.04,
117.32, 120.66, 121.78, 122.29, 123.93, 125.60, 127.85, 129.05, 130.37,
130.52, 130.89, 131.31, 134.17, 147.43, 148.33, 148.44, 160.44. HR-MS
(70 eV, EI): C20H13N3O3 [M]þ† found 343.0977; calc. 343.0957.
Compound 4r: 4H-Naphtho[1,2-b]pyran-3-carbonitrile,2-amino-4-(4-tri-
flouromethylphenyl), mp ¼ 243–46 8C (dec.). IR (KBr, cm21) 3481, 3334,
2187, 1670, 1639, 1602. 1H NMR (300 MHz, acetone-d6, ppm): d 5.09
(s, 1H, H-4), 6.58 (brs, 2H, NH2), 7.15 (d, 1H, J ¼ 8.5 Hz, H-Ar), 7.55–
7.72 (m, 7H, H-Ar), 7.91 (d, 1H, J ¼ 7.60 Hz, H-Ar), 8.32 (d, 1H,
J ¼ 8.1 Hz, H-Ar). 13C NMR (75 MHz, acetone-d6, ppm) d 57.93, 117.02,
119.08, 120.89, 123.37, 124.39, 125.57, 125.63, 125.68, 125.73 (CF3),
126.06, 126.72, 126.91, 127.74, 128.47, 128.76, 133.49, 143.44, 150.13,
160.23. HR-MS (70 eV, EI): C21H13N2OF3 [M]þ† found 366.0980; calc.
366.0967.
Compound 4s: 1H-Naphtho[2,1-b]pyran-2-carbonitrile,3-amino-1-(4-tri-
fluoromethylphenyl), mp ¼ 215–217 8C (dec.). IR (KBr, cm21): 3470,
3358, 2193, 1739, 1576. 1H NMR (300 MHz, acetone-d6, ppm): d 5.48
(s, 1H, H-4), 6.37 (brs, 2H, NH2), 7.37 (d, 1H, J ¼ 8.9 Hz, H-Ar), 7.41–7.50
(m, 4H, H-Ar), 7.64 (d, 2H, J ¼ 8.2 Hz, H-Ar), 7.84–7.94 (m, 4H, H-Ar),
7.98 (d, 1H, J ¼ 8.9 Hz, H-Ar). 13C NMR (75 MHz, acetone-d6, ppm) d
58.93, 114.75, 116.82, 119.16, 122.59, 123.55, 125.12, 125.73, 127.25,
127.96, 128.15, 128.60, 130.00, 130.59, 131.48, 147.40, 149.96, 159.79.
HR-MS (70 eV, EI) C21H13N2OF3 [M]þ† found 366.0980; calc. 366.0967.

1088
S. Balalaie et al.
ACKNOWLEDGMENTS
Saeed Balalaie is grateful to the Alexander von Humboldt Foundation for the
research fellowship and equipment donation. We are thankful to Prof.
M. Yalpani for all of his kind guidance, useful discussions, and support in
International Scientific Meeting Office (ISMO).
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