Microwave-assisted synthesis of 1,8-naphthalic anhydride and fluorescent probes based on its derivatives

Article abstract of DOI:10.1007/s00706-009-0160-4

Efficient synthesis of fluorescent probes based on 1,8-naphthalic anhydride from acenaphthene with the help of microwave irradiation is described. Application of microwave dielectric heating helped improve the yield of the products (>85%) and also reduced the formation of undesired side-products.

Full text of DOI:10.1007/s00706-009-0160-4

Monatsh Chem (2009) 140:1209–1215
DOI 10.1007/s00706-009-0160-4
ORIGINAL PAPER
Microwave-assisted synthesis of 1,8-naphthalic anhydride
and fluorescent probes based on its derivatives
Arvind Misra Æ Mohammad Shahid Æ
Pratibha Dwivedi
Received: 23 October 2008 / Accepted: 22 January 2009 / Published online: 2 July 2009
Ó Springer-Verlag 2009
Abstract Efficient synthesis of fluorescent probes based
on 1,8-naphthalic anhydride from acenaphthene with the
help of microwave irradiation is described. Application of
microwave dielectric heating helped improve the yield
of the products ([85%) and also reduced the formation of
undesired side-products.
the coal industry. Oxidation of acenaphthene, by either
conventional chemical oil-bath [14–17], catalytic [18] or
enzymatic [19–21] procedures under different reaction
conditions, results in the formation of acenaphthylene,
acenaphthenone, acenaphthyleneglycol, acenaphthenequi-
none, and naphthaldehydic and naphthalic acid. The
formation of multiple or side-products during the oxidation
process not only decreases the yield of the major naphthalic
anhydride product but also requires extra purification steps
to isolate the desirable compound in high purity.
Keywords Microwave ꢀ Acenaphthene ꢀ
1,8-Naphthalic anhydride
Thus, an improved chemical procedure for selective
synthesis of 1,8-naphthalic anhydride and its derivatives in
high yield and in shorter time without the formation of
side-products is still elusive. High-speed microwave-
assisted organic synthesis (MAOS) [22–24] has nowadays
become an important tool because of its usefulness in
reducing the chemical reaction time by several orders of
magnitude, in improving the yield of products, and for the
formation of less side-products.
Introduction
1,8-Naphthalic anhydride and its derivatives have been
shown to be promising precursors for the design and syn-
thesis of fluorescent tags [1, 2], polymeric materials [3],
intercalators [4], sensors [5–7], pharmaceutical agents for
the treatment of cancer [8, 9], and dyes [10–12]. The
synthetic approach for the generation of a secondary amine
at the 4-position of naphthalimide-based fluorophores has
wider analytical application in sensing of ions under
physiological condition and is also very useful for internal
charge transfer (ICT) or photoinduced electron transfer
(PET) properties in a molecule [13]. Thus, interest has
grown in optimizing a chemical process for the rapid
synthesis of 1,8-naphthalic anhydride and its derivatives in
high purity and yield. The most convenient way to obtain
naphthalic anhydride or its derivatives is by oxidation of
acenaphthene, a readily available byproduct of processes in
The present paper utilizes microwave (lW) irradiation
for the synthesis of 1,8-naphthalic anhydride derivatives as
potential fluorescent tags or probes for labeling of bio-
molecules and as fluorogenic chemosensors for the
recognition of biologically and environmentally important
analytes under physiological conditions. The products are
obtained through aqueous work-up procedure in high yield
and were purified by simple crystallization rather than
chromatographic methods.
Results and discussion
A. Misra (&) ꢀ M. Shahid ꢀ P. Dwivedi
Nucleic Acids Research Laboratory,
Department of Chemistry, Faculty of Science,
Banaras Hindu University, Varanasi 221005, India
e-mail: arvindmisra2003@yahoo.com
1,8-Naphthalic-anhydride-based fluorescent probes syn-
thesized under both oil-bath as well as lW conditions are
described in Scheme 1. 5-Nitroacenaphthene (2) was
123

1210
A. Misra et al.
Scheme 1
O
N
O
O
N
O
NH
OH
HN
NH2
n
NO2
5a-5d
1
2
O
N
O
O
O
O
O
N
O
O2N
HN
NO2
7
HO
O
4
3
N
O
O
N
O
HO
O
N
NH2
O
O
NO2
NH
O
N
13
NH2
S
OH
O
NO2
N
N
H
14
O
O
8
10
9
N
O
n
N
H
O
a 1
b 2
c 5
d 7
N
O
12
NH2
n
HN
11a-11d
prepared as described previously [2, 10, 25, 26] in 70%
yield. Compound 2 was oxidized in the presence of sodium
dichromate in acetic acid as an oxidizing reagent, under
both experimental conditions, to afford 4-nitro-1,8-naph-
thalic anhydride (3). This oxidation procedure is very well
established but, as reported previously, the reaction is time
consuming and the overall yield of anhydride product
[10–12, 14–16] suffers from the formation of different
intermediate and byproducts as discussed above.
of lW exposure. For precipitation water was added to the
reaction mixture, which on further acid treatment and
washing with water afforded crystalline 4-nitro-1,8-naph-
thalic anhydride in 85% yield. Neither 1H nuclear magnetic
resonance (NMR) nor infrared (IR) spectra showed char-
acteristic peaks for the formation of carboxylic acid or
acenaphthenequinone products, as established previously.
Further, since we analyzed the formation of the desired
products after every 5.0 min of lW irradiation, the forma-
tion of these intermediates is ruled out because, if such
intermediates were formed during the course of reaction,
they would be converted to anhydride product under high-
energy lW conditions.
A kinetic graph was plotted (Fig. 1) for the percentage
yield of the desired product at different time intervals and
molar ratio of oxidizing reagent. It was observed that, after
60 min of complete lW irradiation, a 1:2 molar ratio of
sodium dichromate to substrate 2 led to only *60% con-
version of 4-nitroacenaphthene to 4-nitro-1,8-naphthalic
anhydride (3). However, when the oxidation reaction was
repeated in 1:2.5 molar ratio, compound 3 was obtained in
85% yield after 36 min of lW irradiation at temperature of
80°C. Further increase in concentration of sodium dichro-
mate with extended lW exposure time and higher
temperature up to 120°C did not result in any significant
increase in the yield of product. Thus, a 1:2.5 molar ratio of
oxidizing reagent to 5-nitroacenaphthene (2) was found to
The molar ratio of oxidizing reagent corresponding to the
substrate molecule is crucial under the reaction condition.
Under oil-bath conditions, although the excess amount of
oxidizing reagent is helpful in getting 1,8-naphthalic
anhydride derivatives in higher yield, the use of excess
oxidizing reagent also promotes the formation of different
products and ring destruction [27]. Therefore, we first
optimized the molar concentration of the oxidizing reagent
under lW conditions by treating 5-nitroacenaphthene with
variable molar concentrations of sodium dichromate. To
optimize reaction condition, initially, each lW exposure
was applied in multiples of 30 s and after each exposure the
reaction vials were withdrawn, kept in ice-bath, and allowed
to cool at room temperature before the next lW exposure.
The progress of reaction was monitored by thin-layer
chromatography (TLC). The percentage yield for the for-
mation of anhydride product in different reaction vials was
estimated after 5, 10, 15, 20, 25, 30, 35, 40, 50, and 60 min
123

Microwave-assisted synthesis of 1,8-naphthalic anhydride
1211
we were able to isolate the product in 87% yield when the
same reaction was repeated under lW condition at 80°C
for 15 min.
For the synthesis of 4-amino substituted naphthalic
anhydride derivatives, 4-nitro-N-methyl-1,8-naphthalimide
(4) was reacted with excess amounts of different amino
derivatives such as benzylamine, 2-aminobenzenethiol,
2-methyl-2-aminopropanol, 9,10-bis(aminomethyl)anthra-
cene, and diamines [H2N(CH2)nCH2NH2, n = 1, 2, 5, 7]
under both experimental conditions. In oil-bath condi-
tion on refluxing the reaction mixture (at 110–115°C)
in pyridine or N,N0-dimethylformamide (DMF) solvent,
containing catalytic amounts of triethylamine (TEA), the
rate of substitution reaction was slow and the yield of
different products 5–9 was in the range of 60–75%
(Table 1). Similar types of substitution reactions were
carried out in earlier reported procedures and were also
found to be time consuming and with moderate yield
[11, 26, 29, 32–35].
Fig. 1 Change in percentage yield for the formation of 4-nitro-1,8-
naphthalic anhydride by oxidation of 5-nitroacenaphthene with
sodium dichromate under lW exposure at the ratio of 1:1 closed
diamond; 1:1.5 closed square; 1:2 closed triangle; 1:2.5 open
triangle; 1:3 open square, and 1:3.5 open circle
be optimum, instead of the 1:4 ratio required in the case of
oil-bath processing, to obtain 4-nitro-1,8-naphthalic anhy-
dride (3) in high yield.
Thus, for efficient synthesis of these derivatives we
applied lW conditions under different solvent systems and
at variable temperatures. When we varied the percentage of
TEA as a catalyst in acetonitrile (ACN), tetrahydrofuran
(THF), DMF, and dimethylsulfoxide (DMSO) as solvents
under variable conditions of temperature and lW exposure,
the reactions delivered the product either in low yield or
failed completely. However, when we carried out the
reaction in DMF and 2-methoxyethanol (2-ME) as the
solvent system (1:1; v/v) without employing any catalyst,
The synthesis of 1,8-naphthalic anhydride derivatives
5–14 was carried out either from 4-nitro-1,8-naphthalic
anhydride (3) or 4-nitro-N-methyl-1,8-naphthalimide (4)
precursors under both lW as well as oil-bath experimental
conditions. 4-Nitro-N-methyl-1,8-naphthalimide (4) was
obtained in 60% yield by refluxing compound 3 in ethanol
with methylamine at 60°C for 3 h [26, 28–31]. However,
Table 1 Experimental
Derivatives
Time
CM (h) [lW (min)]
Solvents/temperature (°C)
CM [lW]
Yield (%)
CM [lW]
conditions and yields of
different derivatives synthesized
under oil-bath and lW reaction
conditions
3
3–4 [36]
3 [15]
AcOH/100 [AcOH/80]
50–60 [85]
60 [87]
4
EtOH/TEA/60 [1,4-dioxane/TEA/80]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
EtOH/TEA/60 [1,4-dioxane/TEA/80]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
Py or DMF/TEA/115 [DMF/2-ME/120]
EtOH/TEA/60 [1,4-dioxane/TEA/80]
Py or DMF/TEA/115 [DMF/2-ME/120]
5a
5b
5c
5d
6
4–5 [15]
4–5 [15.3]
4–5 [16.3]
4–5 [16.3]
3–4 [15]
5 [16]
60–65 [88]
60–65 [89]
60–65 [88]
60–65 [86]
60 [78]
7
75 [90]
8
3 [14]
70 [87]
9
5.5 [17.3]
3 [15]
65 [82]
10
11a
11b
11c
11d
12
13
14
83 [89]
4–5 [15.6]
4–5 [15.3]
4–5 [16.1]
4–5 [16.3]
4 [15]
65–68 [86]
65–68 [84]
65–68 [80]
65–68 [79]
66 [80]
3 [15]
61 [85]
3 [14]
63 [86]
123

1212
A. Misra et al.
products 5–9 were obtained selectively in high yields at
120°C within 18 min of total lW exposure. After comple-
tion of the reaction the crude products were poured in ice-
cold water to obtain crystalline compounds, which were
further purified by recrystallization except in the case of
4-(1,1-dimethyl-2-hydroxyethyl)amino-N-methyl-1,8-naphtha-
limide (6). The desired compound was extracted with
ethylacetate (5 9 20 cm3) as a thick yellow oil which was
comprehensively stirred with petroleum ether (3 9 15 cm3)
and dried overnight under vacuum to obtain 6 as off-white-
color gummy mass. Since the reactions were carried out
using 4-nitro-N-methyl-1,8-naphthalimide (4) as precursor,
all the products were obtained selectively by simple aque-
ous work-up and crystallization process. The desired
products 5–9 were characterized and data for 5a were found
to be similar to under oil-bath condition [36].
molecules by direct substitution reaction under lW. The
synthesized probes have potential applications in molecular
biology and analytical chemistry either as fluorescent tags or
as sensors for ions. Some of them have shown very strong
photophysical characteristics, which will be communicated
elsewhere.
Experimental
General
Microwave-assisted synthesis was performed in an ETHOS
1600 (MLS, Milestone, 2.45 GHz, Italy) microwave unit
having provision for temperature regulation and pressure
release. Microwave irradiation reaction was carried out in a
quartz reaction vial. The temperature of the stirred reaction
mixture was monitored directly by fiber-optic temperature
probe inserted into the reaction vial. lW irradiation used:
initial power 300 W for 5 min (ramping); final power
To extend further the application of lW heating, prepa-
rations of other fluorescent compounds 11–14 starting from
4-nitro-1,8-naphthalic anhydride precursor 3 were carried
out. Under these conditions compound 3 with different
amino derivatives employed was found to be prone to two
types of reaction: one associated with the anhydride func-
tionality and the other one with substitution reaction at the
4-nitro position. In general, we observed that, under both
oil-bath and lW reaction conditions, at around 80°C tem-
perature range all the amino derivatives first reacted with the
anhydride functionality of the ring to form naphthalimide
derivatives, which on further temperature increase of the oil-
bath condition to 100°C resulted in a mixture of products and
was also found to be time consuming. Thus, compound 3
was selectively reacted (in 1:1 ratio) with benzylamine and
2-methyl-2-aminopropanol at 80°C under lW (three times
for 5 min) and progress of reaction was monitored by TLC.
4-Nitro-N-alkyl-1,8-naphthalimide derivatives 10 and 13
were obtained exclusively in more than 80% yield (Table 1)
while the remaining unreacted part, after TLC and spectro-
scopic analysis, was found to be unreacted precursor without
any trace of nitro substituted product. Compound 10 was
characterized and data were found to be identical to previ-
ously reported ones [37]. Thus, the lW reaction condition
was found ideal for selective formation of products 10 and
13. The naphthalimide derivatives 10 and 13 on further
reaction (in 1:1.5 ratio) at higher temperature (120°C) under
lW exposure (12-17 min) reacted with benzylamine, dia-
mines, and 2-methyl-2-aminopropanol to give 4-amino-1,8-
naphthalimide derivatives in high yields. All the products
were isolated by simple aqueous work-up and crystallization
procedures, excluding compounds 6 and 14.
1
300 W; temperature and time as specified in Table 1. H
NMR spectra were recorded on a JEOL AL300 FT-NMR
(300 MHz) spectrometer using tetramethylsilane (TMS) as
internal reference. IR spectra in KBr were recorded by
using a Varian-3100 FT-IR spectrometer. Elemental anal-
ysis was carried out on a CE-440 CHN Analyser (Exeter
Analytical Inc.). The results were found to be in good
agreement ( 0.5%) with the calculated values. Melting
points were recorded by open glass capillary method. All
the chemicals used were of reagent grade. Silica Gel G was
used for TLC.
4-Nitro-1,8-naphthalic anhydride (3)
4-Nitroacenaphthene [2] (1.99 g, 10.0 mmol) and
Na2Cr2O7 (6.55 g, 25 mmol) were mixed with of acetic
acid (8.4 g, 140 mmol) and subjected to lW irradiation for
36 min. After completion of reaction (monitored by TLC),
20 cm3 cold water was added to the reaction mixture. The
precipitate obtained was filtered off and treated with 10%
dil. HCl solution to remove completely chromate ester or
chromic acid formed during the reaction, followed by water
washing. Recrystallization from minimum amount of hot
acetic acid (*5 cm3) afforded 3 in 85% yield (Table 1).
M.p. 227°C (Ref. [2]: 229°C).
General procedure for synthesis of fluorescent probes
Methyl amine, benzyl amine or 2-amino-2-methyl-1-pro-
panol (in case of 4, 10, and 13) (1.1 mmol) was added to
4-nitro-1,8-naphthalic anhydride (0.243 g, 1.0 mmol) in
5 cm3 1,4-dioxane in separate quartz reaction vials and
subjected to lW irradiation for a total time period as given in
Table 1. After completion of the reaction (monitored by
Thus, an efficient method has been developed for the
clean oxidation of acenaphthene to the corresponding
anhydride derivatives under microwave irradiation. The
4-nitro-1,8-naphthalic anhydride precursor was successfully
utilized for synthesis of a variety of potential fluorescent
123

Microwave-assisted synthesis of 1,8-naphthalic anhydride
1213
TLC), 10–15 cm3 cold water was added to the reaction
mixture to get precipitation. The precipitates obtained were
washed with 3 9 15 cm3 10% Na2CO3 solution followed by
water, dried under vacuum, and recrystallized from acetic
acid.
J = 8.4 Hz, naphthyl-H), 7.63 (t, J = 7.8 Hz, naphthyl-H),
6.76 (d, J = 8.4 Hz, naphthyl-H), 6.02 (br, NH), 4.21 (br,
NH2), 3.65 (s, CH3), 3.41 (t, J = 5.4 Hz, CH2), 3.18 (t,
J = 5.4 Hz, CH2), 2.21 (m, CH2) ppm; 13C NMR
(75.45 MHz, CDCl3): d = 26.6 (CH3), 27.3, 27.7, 29.9,
30.0, 32.1, 34.3, 40.1, 43.3 (8 CH2), 104.4, 110.6, 120.7,
122.7, 124.9, 126.5, 129.5, 131.4, 134.5, 149.4 (10
C-naphthyl), 164.4, 164.9 (2 C=O) ppm.
In the next step, different amine derivatives (1.5 mmol)
were added to 4-nitro-N-alkyl-1,8-naphthalimide (1 mmol)
using 2-methoxyethanol and dimethylformamide as solvent
mixture (3 cm3; 1:1, v/v) in different quartz reaction vials
and subjected to lW exposure for a total time period
as mentioned in Table 1. After completion of reaction
(monitored by TLC), cold water was added to the reaction
mixture to precipitate out the respective products, which
were recrystallized from acetic acid in high yield. In case
of compound 9 recrystallization was done in chloroform.
Data for compounds 4, 5a, 8, 10, and 12 were found
identical to those reported earlier [10, 11, 26, 32–37].
4-[(1,1-Dimethyl-2-hydroxyethyl)amino]-N-methyl-1,
8-naphthalimide (6, C17H18N2O3)
Rf = 0.53 (EtOAc:n-hexane = 4:6, v/v); IR (KBr):
ꢀ
m = 3,424; 2,925; 2,858; 2,563; 1,737; 1,629; 1,578;
1,396; 1,159 cm-1 1H NMR (300.40 MHz, CDCl3):
;
d = 8.57 (d, J = 7.2 Hz, naphthyl-H), 8.44 (d, J =
8.4 Hz, naphthyl-H), 8.07 (d, J = 8.4 Hz, naphthyl-H),
7.58 (t, J = 7.8 Hz, naphthyl-H), 6.74 (d, J = 8.4 Hz,
naphthyl-H), 5.56 (br, NH), 3.64 (s, CH3), 3.31 (s,
CH2OH), 3.2 (br, OH), 1.12 (s, CH3) ppm; 13C NMR
(75.45 MHz, CDCl3): d = 23.3 (2 CH3), 26.7 (CH3), 52.3
(C-NH), 68.5 (C-OH), 106.4, 112.3, 121.3, 125.9, 127.9,
129.9, 130.3, 135.3, 137.6, 149.5 (10 C-naphthyl), 165.2,
165.5 (2 C=O) ppm.
4-[(3-Aminopropyl)amino]-N-methyl-1,8-naphthalimide
(5b, C16H17N3O2)
ꢀ
M.p. 121°C; Rf = 0.11 (EtOAc); IR (KBr): m = 3,452;
3,257; 3,045; 1,674; 1,580; 1,367; 1,237; 781, 678 cm-1
;
1H NMR (300.40 MHz, CDCl3): d = 8.58 (d, J = 7.2 Hz,
naphthyl-H), 8.44 (d, J = 8.4 Hz, naphthyl-H), 8.10 (d,
J = 8.4 Hz, naphthyl-H), 7.63 (t, J = 7.8 Hz, naphthyl-H),
6.75 (d, J = 8.4 Hz, naphthyl-H), 6.01 (br, NH), 4.20 (br,
NH2), 3.69 (s, CH3), 3.43 (t, J = 5.4 Hz, CH2), 3.21 (t,
J = 5.4 Hz, CH2), 2.31 (m, CH2) ppm; 13C NMR
(75.45 MHz, CDCl3): d = 26.6 (CH3), 32.4, (CH2), 40.3
(C-NH2), 43.4 (C-NH), 104.4, 110.3, 120.7, 122.5, 124.3,
126.5, 129.7, 131.5, 134.5, 149.5 (10 C-naphthyl), 164.2,
164.5 (2 C=O) ppm.
4-(Benzylamino)-N-methyl-1,8-naphthalimide
(7, C20H16N2O2)
M.p. 160°C; Rf = 0.45 (EtOAc:n-hexane = 4:6, v/v); IR
ꢀ
(KBr): m = 3,271; 3,025; 1,673; 1,569; 1,515; 1,375;
1,248 cm-1 1H NMR (300.40 MHz, CDCl3): d = 8.59
;
(d, J = 7.2 Hz, naphthyl-H), 8.46 (d, J = 8.4 Hz, naph-
thyl-H), 8.10 (d, J = 8.4 Hz, naphthyl-H), 7.63 (t,
J = 7.8 Hz, naphthyl-H), 6.76 (d, J = 8.4 Hz, naphthyl-
H), 7.42 (m, Ar-H), 5.59 (br, NH), 4.63 (s, CH2), 3.67 (s,
CH3) ppm; 13C NMR (75.45 MHz, CDCl3): d = 26.8
(CH3), 48.0 (C-NH), 104.9, 110.9, 120.3, 123.1, 124.8,
125.8, 127.7 (7 C-naphthyl), 128.1 (C-phenyl), 129.0 (2 C-
phenyl), 129.6 (2 C-phenyl), 131.1, 134.3, (2 C-naphthyl),
137.0 (C-phenyl), 148.9 (C-naphthyl), 164.3, 164.9 (2
C=O) ppm.
4-[(6-Aminohexyl)amino]-N-methyl-1,8-naphthalimide
(5c, C19H23N3O2)
ꢀ
M.p. 116°C; Rf = 0.12 (EtOAc); IR (KBr): m = 3,464;
3,292; 3,037; 1,691; 1,559; 1,355; 1,242; 745, 655 cm-1
;
1H NMR (300.40 MHz, CDCl3): d = 8.57 (d, J = 7.2 Hz,
naphthyl-H), 8.45 (d, J = 8.4 Hz, naphthyl-H), 8.10 (d,
J = 8.4 Hz, naphthyl-H), 7.63 (t, J = 7.8 Hz, naphthyl-H),
6.76 (d, J = 8.4 Hz, naphthyl-H), 6.03 (br, NH), 4.22 (br,
NH2), 3.66 (s, CH3), 3.42 (t, J = 5.4 Hz, CH2), 3.19
(t, J = 5.4 Hz, CH2), 1.91 (m, CH2) ppm; 13C NMR
(75.45 MHz, CDCl3): d = 26.7 (CH3), 27.1, 27.3, 29.4,
33.5, 40.8, 43.3 (6 CH2), 104.6, 110.3, 120.3, 122.7, 124.5,
126.5, 129.6, 131.6, 134.4, 149.1 (10 C-naphthyl), 164.4,
164.8 (2 C=O) ppm.
4-[[[(10-Aminomethyl)anthracen-9-yl]methyl]amino]-N-
methyl-1,8-naphthalimide (9, C29H23N3O2)
1
M.p. 210°C; Rf = 0.23 (CHCl3:n-hexane = 1:1, v/v); H
NMR (300.40 MHz, CDCl3): d = 8.60 (d, J = 7.2 Hz,
naphthyl-H), 8.51 (dd, J = 6.9 Hz anthracenyl-H), 8.46 (d,
J = 8.4 Hz, naphthyl-H), 8.11 (d, J = 8.4 Hz, naphthyl-
H), 7.65 (t, J = 7.8 Hz, naphthyl-H), 7.59 (dd, J = 6.9 Hz,
anthracenyl-H), 6.76 (d, J = 8.4 Hz, naphthyl-H), 6.01 (br,
NH), 3.63 (s, CH3), 3.81 (br, NH2), 4.10 (s, CH2) ppm; 13
C
4-[(8-Aminooctyl)amino]-N-methyl-1,8-naphthalimide
(5d, C21H27N3O2)
NMR (75.45 MHz, CDCl3): d = 26.6 (CH3), 41.4
(C-NH2), 49.9 (C-NH), 105.3, 111.2, 120.7, 123.5 (4
C-naphthyl), 124.3 (4 C-anthracenyl), 124.9 (C-naphthyl),
125.8 (4 C-anthracenyl), 126.0, 127.6 (2 C-naphthyl),
129.7 (2 C-anthracenyl), 131.1 (C-naphthyl), 131.5
ꢀ
M.p. 110°C; Rf = 0.12 (EtOAc); IR (KBr): m = 3,399;
3,244; 3,035; 1,652; 1,575; 1,344; 1,251; 7,792; 662 cm-1
;
1H NMR (300.40 MHz, CDCl3): d = 8.59 (d, J = 7.2,
naphthyl-H), 8.44 (d, J = 8.4 Hz, naphthyl-H), 8.11 (d,
123

1214
A. Misra et al.
(4 C-anthracenyl), 134.5, 149.3 (2 C-naphthyl), 164.5,
164.8 (2 C=O) ppm.
4-[(8-Aminooctyl)amino]-N-benzyl-1,8-naphthalimide
(11d, C27H31N3O2)
M.p. 119°C; Rf = 0.1 (EtOAc); IR (KBr): m = 3,399;
3,244; 3,035; 1,672; 1,639; 1,575; 1,344; 1,251; 779 cm-1
ꢀ
4-[(2-Aminoethyl)amino]-N-benzyl-1,8-naphthalimide
(11a, C21H19N3O2)
;
1H NMR (300.40 MHz, CDCl3): d = 8.54 (d, J = 7.2 Hz,
naphthyl-H), 8.42 (d, J = 8.4 Hz, naphthyl-H), 8.17 (d,
J = 8.4 Hz, naphthyl-H), 7.58 (t, J = 7.8 Hz, naphthyl-H),
7.52 (d, J = 7.2 Hz, phenyl-H), 7.19 (m, phenyl-H), 6.67
(d, J = 8.7 Hz, naphthyl-H), 6.17 (br, NH), 5.36 (s, CH2),
4.21 (br, NH2), 3.65 (s, CH3), 3.41 (t, J = 5.4 Hz, CH2),
3.18 (t, J = 5.4 Hz, CH2), 2.21 (m, CH2) ppm; 13C NMR
(75.45 MHz, CDCl3): d = 27.5, 27.8, 29.6,30.1, 31.3, 33.9
(6 CH2), 40.7 (C-NH2), 43.9 (C-N), 45.9 (C-NH), 104.5,
110.8, 120.5, 122.6, 124.6, 126.7 (6 C-naphthyl), 127.4
(C-phenyl), 128.8 (2 C-phenyl), 129.1 (2 C-phenyl), 129.8,
131.7, 134.8 (3 C-naphthyl), 137.7 (C-phenyl), 149.8
(C-naphthyl), 164.6, 164.8 (2 C=O) ppm.
ꢀ
M.p. 155°C; Rf = 0.10 (EtOAc); IR (KBr): m = 3,431;
3,257; 3,053; 1,679; 1,633; 1,578; 1,346; 1,296; 772 cm-1
;
1H NMR (300.40 MHz, CDCl3): d = 8.57 (d, J = 7.2 Hz,
naphthyl-H), 8.45 (d, J = 8.4 Hz, naphthyl-H), 8.14 (d,
J = 8.4 Hz, naphthyl-H), 7.58 (t, J = 7.8 Hz, naphthyl-H),
7.52 (d, J = 7.6 Hz, phenyl-H), 7.20 (m, phenyl-H), 6.69
(d, J = 8.7 Hz, naphthyl-H), 6.15 (br, NH), 5.33 (s, CH2),
3.37 (d, J = 5.4 Hz, CH2), 3.12 (t, J = 5.7, 5.4 Hz, CH2)
ppm; 13C NMR (75.45 MHz, CDCl3): d = 40.1 (C-NH2),
43.2 (C-N), 44.8 (C-NH), 104.3, 110.0, 120.4, 122.9, 124.6,
126.3, (6 C-naphthyl), 127.1 (C-phenyl), 128.3 (2 C-phe-
nyl), 128.8 (2 C-phenyl), 129.8, 131.2, 134.6 (3
C-naphthyl), 137.8 (C-phenyl), 149.7 (C-naphthyl), 164.1,
164.6 (2 C=O) ppm.
4-Nitro-N-(1,1-dimethyl-2-hydroxyethyl)-
1,8-naphthalimide (13, C16H14N2O5)
4-[(3-Aminopropyl)amino]-N-benzyl-1,8-naphthalimide
(11b, C22H21N3O2)
M.p. 133°C; Rf = 0.58 (EtOAc:n-hexane = 2:8, v/v); IR
ꢀ
(KBr): m = 3,386; 3,074; 2,921; 1,732; 1,641; 1,565;
1,448; 1,373 cm-1 1H NMR (300.40 MHz, CDCl3):
;
ꢀ
M.p. 147°C; Rf = 0.10 (EtOAc); IR (KBr): m = 3,432;
3,245; 3,045; 1,675; 1,636; 1,574; 1,363; 1,227; 781 cm-1
;
d = 8.65 (d, J = 7.2 Hz, naphthyl-H), 8.56 (d,
J = 8.4 Hz, naphthyl-H), 8.41 (d, J = 7.8 Hz, naphthyl-
H), 8.03 (d, J = 7.8 Hz, naphthyl-H), 7.82 (t, J1 = 7.5 Hz,
J2 = 8.1 Hz, naphthyl-H), 3.31 (s, CH2), 2.81 (br, OH),
1.10 (s, CH3) ppm.
1H NMR (300.40 MHz, CDCl3): d = 8.54 (d, J = 7.2 Hz,
naphthyl-H), 8.44 (d, J = 8.4 Hz, naphthyl-H), 8.15 (d,
J = 8.4 Hz, naphthyl-H), 7.60 (t, J = 7.8 Hz, naphthyl-H),
7.51 (d, J = 7.2 Hz, phenyl-H), 7.21 (m, phenyl-H), 6.69 (d,
J = 8.7 Hz, naphthyl-H), 6.16 (br, NH), 5.36 (s, CH2), 4.20
(br, NH2), 3.69 (s, CH3), 3.43 (t, J = 5.4 Hz, CH2), 3.21 (t,
J = 5.4 Hz, CH2), 2.31 (m, CH2) ppm; 13C NMR
(75.45 MHz, CDCl3): d = 31.8, (CH2), 40.3 (C-NH2), 43.5
(C-N), 44.7 (C-NH), 104.5, 110.3, 120.7, 122.6, 124.7, 126.7,
(6 C-naphthyl), 127.3(C-phenyl), 128.6 (2 C-phenyl), 128.6
(2 C-phenyl), 129.7, 131.5, 134.7 (3 C-naphthyl), 137.5
(C-phenyl), 149.8 (C-naphthyl), 164.5, 164.8 (2 C=O) ppm.
4-[(1,1-Dimethyl-2-hydroxyethyl)amino]-
N-(1,1-dimethyl-2-hydroxyethyl)-1,8-naphthalimide
(14, C16H14N2O5)
Rf = 0.41 (EtOAc:n-hexane = 4:6, v/v); IR (KBr):
ꢀ
m = 3,426; 2,921; 2,852; 2,568; 1,735; 1,626; 1,575;
1,394 cm-1 1H NMR (300.40 MHz, CDCl3): d = 8.36
;
(d, J = 7.2 Hz, naphthyl-H), 8.18 (d, J = 8.4 Hz, naphthy-
Hl), 7.74 (d, J = 8.4 Hz, naphthyl-H), 7.58 (t, J = 7.8 Hz,
naphthyl-H), 6.72 (d, J = 8.4 Hz, naphthyl-H), 6.20 (br,
NH), 4.12 (br, OH), 3.28 (s, CH2OH), 1.10 (s, CH3) ppm;
13C NMR (75.45 MHz, CDCl3): d = 22.9 (2 CH3), 23.1 (2
CH3), 43.8 (C-N), 56.3 (C-NH), 66.2, 67.8 (C-OH), 124.3,
125.9, 127.0, 127.8, 128.8, 129.9, 130.2, 132.7, 135.3,
147.6 (10 C-naphthyl), 165.0, 165.4 (2 C=O) ppm.
4-[(6-Aminohexyl)amino]-N-benzyl-1,8-naphthalimide
(11c, C25H27N3O2)
ꢀ
M.p. 130°C; Rf = 0.10 (EtOAc); IR (KBr): m = 3,464;
3,292; 3,037; 1,691; 1,630; 1,559; 1,355; 1,242; 745 cm-1
;
1H NMR (300.40 MHz, CDCl3): d = 8.51 (d, J = 7.2 Hz,
naphthyl-H), 8.45 (d, J = 8.4 Hz, naphthyl-H), 8.14 (d,
J = 8.4 Hz, naphthyl-H), 7.58 (t, J = 7.8 Hz, naphthyl-H),
7.52 (d, J = 7.2 Hz, phenyl-H), 7.20 (m, phenyl-H), 6.68
(d, J = 8.7 Hz, naphthyl-H), 6.17 (br, NH), 5.36 (s, CH2),
4.22 (br, NH2), 3.66 (s, CH3), 3.42 (t, J = 5.4 Hz, CH2),
3.19 (t, J = 5.4 Hz, CH2), 1.91 (m, CH2) ppm; 13C NMR
(75.45 MHz, CDCl3): d = 27.3, 27.5, 29.7, 33.7 (4 CH2),
40.6 (C-NH2), 43.7 (C-N), 45.6 (C-NH), 104.7, 110.6,
120.9, 122.2, 124.9, 126.8 (6 C-naphthyl), 127.5
(C-phenyl), 128.7 (2 C-phenyl), 128.9 (2 C-phenyl),
129.6, 131.6, 134.9 (3 C-naphthyl), 137.9 (C-phenyl),
149.6 (C-naphthyl), 164.3, 164.6 (2 C=O) ppm.
Acknowledgments The authors are thankful to the Department of
Science and Technology, New Delhi, India for financial assistance
and also acknowledge SAP, University Grant Commission (UGC)
New Delhi, for spectroscopic facilities in the Department.
References
1. Dubey KK, Singh RK, Misra K (1997) Neurochem Int 31:405
2. Singh Y, Misra A, Misra K (2002) Ind J Chem 41B:1238
3. Niu CG, Li ZZ, Zhang XB, Lin WQ, Shen GL, Yu RQ (2002)
Anal Bioanal Chem 372:519
123

Microwave-assisted synthesis of 1,8-naphthalic anhydride
1215
4. Brana MF, Cacho M, Ramos A, Dominguez MT, Pozuelo JM,
Abradelo C, Rey-Stolle MF, Yuste M, Carraso C, Baily C (2003)
Org Biomol Chem 1:648
22. Tierney LJ, Wathey B, Westman J (2001) Tetrahedron 57:9225
23. Nuchter M, Ondruschka B, Bonrath W, Gum A (2004) Green
Chem 6:128
5. Gunnlaugsson T, Kruger PE, Jensen-Tierney PJ, Ali HDP,
Hussey GM (2005) J Org Chem 70:10875
6. Martinez Manez R, Sancenon F (2003) Chem Rev 103:4419
7. Prakesh R, Lee TC, Gunnlaugsson T (2007) Org Biomol Chem
5:310
24. Kappe CO (2004) Angew Chem Int Ed 43;6250
25. Okazaki M, Tanaka T, Taniguchi S (1956) Yuki Gosei Kagoaku
Kyokaishi 14:344
26. Dongwu Y, Brown RG, Hepworth JW, Alexiou MS, Tyman JHP
(2008) J Heterocycl Chem 45:397
8. Kamal A, Reddy BSN, Reddy GSK, Ramesh G (2002) Bioorg
Med Chem Lett 12:1933
9. Carrasco C, Joubert A, Tardy A, Maestre N, Cacho M, Brana MF,
Bailly CA (2003) Biochemistry 42:11751
10. Grayshan PH, Peters AT (1971) J Chem Soc C 3599
11. Grayshan PH, Khadhim AM, Peters AT (1974) J Heterocycl
Chem 11:33
27. Friedman L, Fishel DL, Shechter H (1965) J Org Chem 30:1453
28. Bojinov VB, Georgiev NI, Nikolov PS (2008) J Photochem
Photobiol A Chem 193:129
29. Elbert JE, Paulsen S, Robinson L, Elzy S, Kristen K (2005) J
Photochem Photobiol A Chem 169:9
30. Parkesh R, Lee TC, Gunnlaugsson T (2007) Org Biomol Chem
5:310
12. Khosravi A, Moradian S, Gharanjig K, Taromi FA (2006) Dyes
Pigments 69:79
31. Khosravi A, Moradian S, Ghoranjig K, Taromi AF (2006) Dyes
Pigments 69:79
13. Gunnlaugsson T, Glynn M, Tocci GM, Kruger PE, Pfeffer FM
(2006) Coord Chem Rev 250:3094
32. Bojinov VB, Konstantinova TN (2007) Sensors and Actuators B:
Chemical 123:869
14. Graebe C, Briones N (1903) Annalen 327:80
15. Behr A, Van Drop WA (1873) Ber 6:60
16. Hahn DA, Holmes HE (1921) J Ind Eng Chem 13:822
17. Cason J, Wordie JD (1953) J Org Chem 18:1594
18. Bukharkina TV, Grechishkina OS, Digurov NG, Kon’kov II
(2002) Org Proc Res Dev 6:394
19. Selifonov SA, Grifoll M, Eaton RW, Chapman P (1996) Appl
Environ Microbiol 62:507
20. Johannes C, Majcherczyk A, Huttermann A (1998) J Biotech
61:151
21. Hopkins RP, Young L (1996) Biochem J 98:19
33. Xu Z, Qian X, Cui J, Zhang R (2006) Tetrahedron 62:10117
34. Wnag J, Xiao Y, Zhang Z, Qian X, Yang Y, Xu Q (2005) J Mater
Chem 15:2836
35. Konstantinova T, Spirieva A, Petkova T (2000) Dyes Pigments
45:125
36. Fan J, Peng X, Wu Y, Lu E, Hou J, Zhang H, Zhang R, Fu X
(2005) J Lumin 114:125
37. Costi MP, Tondi D, Rinaldi M, Barlocco D, Cignarella G, Santi
DV, Musiu C, Pudu I, Vacca G, La colla P (1996) Eur J Med
Chem 31:1011
123