Efficient sonochemical synthesis of 3- and 4-electron withdrawing ring substituted N-alkyl-1,8-naphthalimides from the related anhydrides

Article abstract of DOI:10.1081/SCC-120037911

1,8-N-alkyl-naphthalimides substituted with electron withdrawing groups were readily prepared in high yields using ultrasound in aqueous media.

Full text of DOI:10.1081/SCC-120037911

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Efficient Sonochemical Synthesis of 3‐ and
4‐Electron Withdrawing Ring Substituted
N‐Alkyl‐1,8‐naphthalimides from the Related
Anhydrides
a
a
a
Eduardo Rezende Triboni , Pedro Berci Filho , Roberto Gomes de Souza Berlinck
&
b
Mario José Politi
a
Instituto de Química de São Carlos , Universidade de São Paulo , CP 780, CEP
1
3560‐970, São Carlos, SP, Brazil
b
Instituto de Química , Universidade de São Paulo , São Paulo, SP, Brazil
Published online: 20 Aug 2006.
To cite this article: Eduardo Rezende Triboni , Pedro Berci Filho , Roberto Gomes de Souza Berlinck & Mario José Politi
2004) Efficient Sonochemical Synthesis of 3‐ and 4‐Electron Withdrawing Ring Substituted N‐Alkyl‐1,8‐naphthalimides
(
from the Related Anhydrides, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:11, 1989-1999, DOI: 10.1081/SCC-120037911
To link to this article: http://dx.doi.org/10.1081/SCC-120037911
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w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 11, pp. 1989–1999, 2004
Efficient Sonochemical Synthesis of 3- and
4
-Electron Withdrawing Ring Substituted
N-Alkyl-1,8-naphthalimides from the
Related Anhydrides
1
Eduardo Rezende Triboni, Pedro Berci Filho,
1,*
1
Roberto Gomes de Souza Berlinck,
2
and Mario Jos e´ Politi
1
Instituto de Qu ´ı mica de S a˜ o Carlos, Universidade de S a˜ o Paulo,
S a˜ o Carlos, SP, Brazil
Instituto de Qu ´ı mica, Universidade de S a˜ o Paulo, S a˜ o Paulo
SP, Brazil
2
ABSTRACT
1,8-N-alkyl-naphthalimides substituted with electron withdrawing groups
were readily prepared in high yields using ultrasound in aqueous media.
Key Words: N-alkyl-1,8-naphthalimides; Sonochemistry; Aqueous
media; Alkyl derivative; Heterogeneous sonochemistry; Alkyl amines.
*
Correspondence: Pedro Berci Filho, Instituto de Qu ´ı mica de S a˜ o Carlos, Universidade
de S a˜ o Paulo, CP 780, CEP 13560-970, S a˜ o Carlos, SP, Brazil; E-mail: berci@iqsc.usp.br.
1
989
DOI: 10.1081/SCC-120037911
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

ORDER
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1
990
Triboni et al.
INTRODUCTION
Naphthalimide derivatives are quite important as anti-neoplastic and anti-
[
1–3]
viral agents,
hypoxic cells, DNA cleaving agents, and fluorescent reporters ) and
as fluorescent probes for a series of biological (probes of
[5]
[
4]
[6]
[7]
non-biological (optical brighteners, day-light fluorescent pigments ) appli-
cations. Naphthalimides have also been utilized as probes in several biophys-
ical and photophysical studies in both homogeneous and micro-heterogeneous
[
8,9]
media.
Despite numerous studies involving 1,8-naphthalimides, there are very few
[4,10]
routes for the synthesis of N-alkyl derivatives.
methods have been described: the N-alkylation of the 1,8-naphthalimide potass-
Two well-established
[
11]
[10]
ium salt with alkyl halides and a more general method involving the reac-
tion of an amine with 1,8-naphthalic anhydride under reflux, followed by the
cyclization of the corresponding N-substituted amic 1 intermediate [Eq. (1)].
[12]
More sophisticated or recent methods are the Mitsunobu reaction
2)] and the reaction of an aryl azide with naphthalic anhydride in the presence
[Eq.
(
of iodomethylsilane
[
13]
[Eq. (3)].
Substituents on 1,8-naphthalic anhydrides play a decisive role on their
[14]
reactivity toward amines in the overall imidization process, determining
the conditions to be employed, which are largely solvent-dependent.
reactivity pattern follows this “rule of thumb”: N-alkyl-1,8-naphthalimides
[10]
The
bearing electron-donating substituents, such as –OR, –NHR, Cl, and Br,
[17]
[
15,16]
are smoothly obtained in protic solvents like water,
[
methanol,
giving moderate to good yields. On the other hand,
18,19]
and ethanol,

ORDER
REPRINTS
Synthesis of N-Alkyl-1,8-naphthalimides
1991
N-alkyl-1,8-naphthalimides with substituents that withdraw electrons, such as
like DMSO,
[20]
a nitro group, are better prepared in polar aprotic medium
DMSO/THF, DMF, and NMP, giving poor to moderate yields.
The present work reports the aqueous sonochemical synthesis of 4-nitro-
N-alkyl-1,8-naphthalimides and other N-alkyl imides with electron withdraw-
ing sustituents attached on the naphthalene ring.
Sonication of 4-nitro-1,8-naphthalic anhydride in aqueous suspension
employing lower primary amines as nucleophiles gave the corresponding
imides 2e–2i in high yield (Table 1). No amic acid intermediates or nitro dis-
[21]
placement side products could be detected, suggesting a tandem reaction
pattern with high regioselectivity. The reaction mechanism appears to follow
[22]
the proposed pathways for the imidization reaction in protic solvents,
showing no sonochemical switching effect.
[23]
This sonochemical method was also highly effective for the synthesis of
the unsubstituted N-alkyl-1,8-naphthalimide derivatives 2a–2d, as well as for
the 4-chloro 2j–2n (Table 1) and 3-nitro 3a–3d substituted derivatives
(
Table 2 and Sch. 1).
In contrast, no reaction was observed between ethylamine and 4-nitro-
1,8-naphthalic anhydride. This should be due to some intrinsic sonochemical
interference, since this reaction can be carry out by other conventional
Table 1. Derivatives of 4-substituted N-alkyl-1,8-naphthalimides.
a
Product
R
1
R
2
Yield (%)
Time (hr)
b
2
2
2
2
2
2
2
2
2
2
2
2
2
a
b
c
d
e
f
Me
Et
H
84
57
1.5
3
c
H
H
H
d
n-Propyl
n-Butyl
Me
30
41
4
c
2
b
NO
NO
2
96
—
1.5
—
2
Et
2
b
g
h
i
n-Propyl
n-Butyl
Allyl
NO2
75
80
b
NO
NO
Cl
2
2
b
2
85
80
2.5
2
b
j
Me
Et
d
l
Cl
Cl
80
70
2.5
3
d
m
n
n-Propyl
n-Butyl
c
Cl
50
2
a
Isolated yield.
b
c
Without need of purification.
Purified by recrystallization (from ethanol).
Purified by flash chromatography (chloroform/silica-gel); Sonicating bath US
50 W/25 kHz.
d
1

ORDER
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1
992
Triboni et al.
Table 2. Derivatives of 3-nitro-N-alkyl-1,8-naphthalimides.
a
Product
R
1
Yield (%)
Time (hr)
3
3
3
3
a
b
c
Me
Et
95
89
83
71
1.5
1.5
1.5
1.5
n-Propyl
n-Butyl
d
a
Isolated yield with no need of purification. Sonicating bath US 150 W/
5 kHz.
2
synthetic routes and works well to the 3-nitro isomer. The use of an ultrasonic
apparatus with different specifications (150 W/25 kHz and 50 W/45 kHz) did
not cause significant changes in the overall yield or in the reactions time.
Since the aforesaid results would be due simply to a mixing effect, the
same reactions were performed under magnetic stirring conditions (silent
mode), giving very poor yields and in some cases no reaction at all. The sono-
chemical imidization results presented here are in agreement with the litera-
[
24,25]
ture and follow general trend for sonochemical ionic reactions.
study, the undesired solvolytic processes usually provided by sonication
did not interfere with the desired reactions.
In this
[25]
Finally, we studied the extension of this sonochemical procedure to an
aqueous homogeneous solution. Sonication of potassium 4-sulfonic-1,8-
naphthalic anhydride in aqueous solution with n-butylamine led to a more
complex reaction approach (Sch. 2). The sonication with an ultrasonic cleaner
of 50 W and 45 kHz resulted in loss of reaction selectivity, 4-n-butylamino-N-
butyl-1,8-naphthalimide 4c being the only detectable product. At the same
time, the sonication with an ultrasonic cleaner of 150 W and 25 kHz yielded
4-sulfonic-N-butyl-1,8-naphthalimide 4b as the only product (Table 3). The
explanation of this behavior, which is dependent on sonochemical conditions,
requires further studies.
Scheme 1. Imidization of 3- and 4-substituted-1,8-naphthalic anhydrides in hetero-
geneous media. R ¼ methyl, ethyl, n-propyl, n-butyl; R ¼ H, NO , Cl; ))) ¼
2
1
2
sonication.

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REPRINTS
Synthesis of N-Alkyl-1,8-naphthalimides
1993
Scheme 2. Imidization of 4-sulfonic-1,8-naphthalic anhydride in homogeneous
media.
In conclusion, we developed a new sonochemical method for the syn-
thesis of N-alkyl-1,8-naphthalimides in aqueous media, resulting in a shorter
reaction times, a “cleaner” final products and in a greater yields.
EXPERIMENTAL
General Procedures
All 1,8-naphthalic anhydrides were purchased from Aldrich. The amines:
n-butylamine (Carlo Erba), n-propylamine (Acros), Allylamine (Acros),
ethylamine 70% aqueous solution (Fluka), and methylamine 40% aqueous
solution (Fluka) were used without further purification. Water utilized in the
experiments was doubly distilled. Other solvents were of spectroscopic
Table 3. Derivatives of 4-sulfonic-N-alkyl-1,8-naphthalimides.
a
Product
R
1
R
2
Yield (%)
Time (hr)
b
4a
4b
4c
Me
n-Butyl
n-Butyl
SO
SO H
3
H
88
1.5
1.5
0.5
b
85
93
3
c
n-Butyl
a
Isolated yield.
b
US 150 W/25 kHz.
US 50 W/45 KHz.
c

ORDER
REPRINTS
1
994
Triboni et al.
grade and used without further purification. Melting points were determined in
1
an electrothermal melting point apparatus. H-NMR spectra were recorded on
a Bruker AC-200 in CDCl and DMSO-d . The chemical shifts were reported
6
3
as parts per million (d, ppm) from TMS as an internal standard. Infrared (IR)
spectra were recorded on a BOMEM-MB 102-FT-IR spectrometer, employing
KBr plates. Capillary GC analyses were performed on a HP-5890 coupled to a
MSD-5970 mass selective detector. Two ultrasonic cleaner baths (Bransonic)
150 W/25 kHz and 50 kHz/40 kHz were used.
Method A (For Heterogeneous Suspension)
To a suspension of 4- or 3-nitro- or 4-chloro-1,8-naphthalic anhydride
1 mmol for all compounds) and 50 mL of distilled water in a 125-mL Erlen-
(
meyer flask was added 10 mmol of the primary amine. The suspension was
submitted to sonication using an ultrasonic cleaning bath with 150 W and
25 kHz of power and frequency, respectively. In the course of the reaction,
the temperature was kept at 22–258C. After the reaction was completed, a
diluted HCl solution was added and the crude product was filtered off and
washed with water. The products were dried in a vacuum oven.
N-Methyl-1,8-naphthalimide 2a. 84%; white crystals; mp 208–2098C
[
26]
(
literature
¼ 204–2058C); IR (KBr) 3105, 2947, 1699, 1673, 1592,
2
582, 1528, 1353, 1294, 1060 cm , H-NMR (CDCl ) d 3.54 (s, 3H, CH ),
1 1
1
7
3 3
.72 (t, J ¼ 7.8 Hz, 2H, Ar), 8.17 (d, J ¼ 7.8 Hz, 2H, Ar), 8.68
þ
(
anal. calcd for C H NO : N, 6.66; C, 74.23; H, 3.85. Found: N, 6.64; C,
d, J ¼ 7.3 Hz, 2H, Ar); MS (m/z) 211 (M , 100), 183, 167, 127, 75, 63;
1
3
8
2
7
4.13; H, 3.87.
N-Ethyl-1,8-naphthalimide 2b. 57%; white crystals; mp 156–1578C
[
11]
(
literature
¼ 1578C); IR (KBr) 3485, 3057, 2980, 2872, 1696, 1655,
6
2
599, 1540, 1370, 1070 cm , H-NMR (DMSO-d ) d 1.94 (br s, 2H), 4.0
1 1
1
(
br s, 2H), 4.48 (br s, 1H), 7.78 (t, J ¼ 7.8 Hz, 2H, Ar), 8.22 (d, J ¼ 8.1 Hz,
2
H, Ar), 8.61 (d, J ¼ 6.66 Hz, 2H, Ar); MS (m/z) 210, 198 (100), 180, 152,
126, 75, 63; anal. calcd for C H NO : N, 6.25; C, 75.01; H, 4.46. Found:
N, 6.28; C, 74.88; H, 4.46.
1
4
10
2
N-Propyl-1,8-naphthamide 2c. 30%; white crystals; mp 164–1658C
[
11]
(
literature
21 1
346, 1235, 1080 cm , H-NMR (DMSO-d ) d 0.914 (t, 3H, CH ), 1.64 (sex-
¼ 1608C); IR (KBr) 3079, 2961, 2875, 1707, 1661, 1526,
1
tet, 2H, CH ), 4.0 (t, 2H, CH ), 7.85–7.92 (m, 2H, Ar), 8.46–8.51 (m, 4H,
6 3
2
2
þ
Ar); MS (m/z) 239 (M ), 197 (100), 180, 154, 126, 75, 63, 41; anal. calcd
for C H NO : N, 5.88; C, 75.63; H, 5.04. Found: N, 5.85; C, 75.53; H, 5.11.
1
5
12
2
N-Butyl-1,8-naphthalimide 2d. 41%; white crystals; mp 92–948C
[
11]
(
literature
¼ 97–988C); IR (KBr) 3075, 2948, 1697, 1658, 1623, 1589,

ORDER
REPRINTS
Synthesis of N-Alkyl-1,8-naphthalimides
1995
2
1 1
1
2
2
352, 1266, 1073 cm , H-NMR (CDCl ) d 0.94 (t, 3H, CH ), 1.56 (sextet,
3 3
H, CH ), 1.69 (quintet, 2H, CH ), 4.17 (t, 2H, CH ), 7.73 (t, J ¼ 7.5 Hz,
2
2
2
H, Ar), 8.18 (d, J ¼ 8.3 Hz, 2H, Ar), 8.58 (d, J ¼ 7.2 Hz, 2H, Ar); MS (m/
þ
z) 253 (M ), 211, 197 (100), 180, 152, 126, 77; anal. calcd for C H NO :
1
6
14
2
N, 5.55; C, 76.20; H, 5.55. Found: N, 5.47; C, 76.32; H, 5.58.
4
-Nitro-N-methyl-1,8-naphthalimide 2e. 96%; yellow crystals; mp
[
27]
2
1
7
08–2098C (literature
¼ 207–2088C); IR (KBr) 3083, 2956, 1696, 1659,
3 3
21 1
595, 1537, 1336, 1278, 1078 cm , H-NMR (CDCl ) d 3.60 (s, 3H, CH ),
.98 (t, J ¼ 7.9 Hz, 1H, Ar), 8.41 (d, J ¼ 7.9 Hz, 1H, Ar), 8.38
þ
(
d, J ¼ 7.94 Hz, 1H, Ar), 8.67–8.85 (m, 3H, Ar); MS (m/z) 256 (M , 100),
2
10, 198, 182, 153, 125, 99, 75; anal. calcd for C H N O : N, 10.93; C,
13 8 2 4
60. 93; H, 3.09. Found: N, 10.75; C, 61.11; H, 3.07.
4
-Nitro-N-propyl-1,8-naphthalimide 2f. 75%; yellow crystals; mp
[
27]
1
1
0
35–1368C (literature
707, 1661, 1623, 1526, 1346, 1235, 1079 cm . H-NMR (DMSO-d ) d
¼ 135.5–136.58C); IR (KBr) 3079, 2961, 2875,
2
1 1
6
.92 (t, 3H, CH ), 1.65 (sextet, 2H, CH ), 3.98 (t, 2H, CH ), 8.0
3
2
2
þ
(
t, J ¼ 7.3 Hz, 1H, Ar), 8.47-8.72 (m, 4H, Ar); MS (m/z) 284 (100, M ),
243, 255, 209, 179, 151, 126, 75, 41; anal. calcd for C H N O : N, 9.85;
C, 63.38; H, 4.22. Found: N, 9.98; C, 63.60; H, 4.27.
15 12 2 4
4
-Nitro-N-butyl-1,8-naphthalimide 2g. 80%; yellow needles; mp
27]
[
1
1
03.5–1048C (literature
706, 1656, 1624, 1530, 1347, 1231, 1082 cm , H-NMR (CDCl ) d 0.96
¼ 103.5–104.58C); IR (KBr) 3074, 2961, 2872,
3
2
1 1
(
t, 3H, CH ), 1.56 (sextet, 2H, CH ), 1.72 (quintet, 2H, CH ), 4.18 (t, 2H,
3 2 2
CH ), 7.96 (t, J ¼ 8.0 Hz, 1H, Ar), 8.38 (d, J ¼ 8.0 Hz, 1H, Ar), 8.67–8.86
2
þ
(
m, 3H, Ar); MS (m/z) 298 (M , 100), 256, 243, 225, 209, 179, 151, 126,
75; anal. calcd for C H N O : N, 9.39; C, 64.42; H, 4.69. Found: N, 9.33;
C, 64.38; H, 4.72.
16 14 2 4
4
-Nitro-N-allyl-1,8-naphthalimide 2h. 85%; yellow crystals; mp 104–
2
1 1
1
058C; IR (KBr) 3084, 2917, 1708, 1661, 1530, 1336, 1233, 1096 cm , H-
NMR (CDCl ) d 4.83 (d, 2H, CH ), 5.23 (d, 1H, CH ), 5.35 (d, 1H, CH ), 6.0
m, 1H, CH), 7.82 (t, 1H, Ar), 8.41 (d, 1H, Ar), 8.72 (d, 1H, Ar), 8.76 (d, 1H,
3
2
2
2
(
Ar), 8.86 (d, 1H, Ar); MS (m/z) 282 (M ), 267 (100), 237, 221, 179, 151, 125;
þ
anal. calcd for C H N O : N, 9.92; C, 63.83; H, 3.54. Found: N, 10.02; C,
1
6 14 2 4
63.87; H, 3.63.
4
-Chloro-N-methyl-1,8-naphthalimide 2i. 80%; white crystals; mp
[
11]
1
70–1718C (literature
664, 1623, 1569, 1347, 1283, 1034 cm , H-NMR (CDCl ) d 3.55 (s, 3H,
¼ 174–1758C); IR (KBr) 3057, 2951, 2861, 1696,
3
21 1
1
CH ), 7.80–7.91 (m, 2H, Ar), 8.5 (d, J ¼ 7.94 Hz, 1H, Ar), 8.58–8.71 (m, 2H,
3
þ
Ar); MS (m/z) 245 (M , 100), 217, 188, 166, 125, 99, 75, 32; anal. calcd for
C H NClO : N, 5.71; C, 63.56; H, 3.26. Found: N, 5.64; C, 63.48; H, 3.24.
1
3
8
2
4
-Chloro-N-ethyl-1,8-naphthalimide 2j. 80%; white crystals; mp 167–
[
11]
1
688C (literature
¼ 165–1668C); IR (KBr) 3385, 3068, 2968, 2888, 1695,

ORDER
REPRINTS
1
996
Triboni et al.
H-NMR (DMSO-d ) d 3.61
2
1
1
1
660, 1624, 1365, 1235, 1060 cm
,
6
(
q, J ¼ 6.0 Hz, 2H), 4.12 (t, J ¼ 6.3 Hz, 2H), 4.79 (t, J ¼ 6.3 Hz, 1H),
7
.91–8.0 (m, 2H, Ar), 8.37 (d, J ¼ 7.96 Hz, 1H, Ar), 8.50–8.54 (m, 2H,
Ar); MS (m/z) 244, 232(100), 214, 160, 126, 75; anal. calcd for
C H NClO : N, 5.39; C, 64.76; H, 3.85. Found: N, 5.52; C, 64.59; H, 3.82.
1
4
10
2
4
-Chloro-N-propyl-1,8-naphthalimide 2l. 70%; white crystals; mp
[
11]
1
1
0
41–1428C (literature
¼ 142.5–1438C); IR (KBr) 3065, 2952, 2870,
21 1
696, 1664, 1624, 1569, 1352, 1236, 1071 cm , H-NMR (DMSO-d ) d
6
.91 (t, 3H, CH ), 1.63 (sextet, 2H, CH ), 3.97 (t, 2H, CH ), 7.91–8.0
3
2
2
þ
(
m, 2H, Ar), 8.35–8.14 (m, 3H, Ar); MS (m/z) 273 (M ), 231 (100), 214,
1
4
87, 160, 126, 75, 41; anal. calcd for C H NClO : N, 5.12; C, 65.83; H,
15 12 2
.38. Found: N, 5.11; C, 65.73; H, 4.26.
4
-Chloro-N-butyl-1,8-naphthalimide 2m. 50%; white needles; mp 89–
11]
[
9
08C (literature
¼ 92–948C); IR (KBr) 2954, 1701, 1652, 1589, 1461,
3 3
21 1
350, 1076 cm , H-NMR (CDCl ) d 0.95 (t, 3H, CH ), 1.54 (sextet, 2H,
1
CH ), 1.69 (quintet, 2H, CH ), 4.15 (t, 2H, CH ), 7.7–7.9 (m, 2H, Ar),
2
2
2
þ
8
1
.4–8.6 (m, 3H, Ar); MS (m/z) 287 (M ), 247, 231 (100), 214, 186, 160,
26, 75; anal. calcd for C H NClO : N, 4.87; C, 66.80; H, 4.87. Found:
1
6
14
2
N, 4.80; C, 66.95; H, 4.87.
-Nitro-N-methyl-1,8-naphthalimide 3a. 95%; yellow crystals; mp
04–2058C; IR (KBr) 3083, 2956, 1696, 1659, 1624, 1537, 1336, 1278,
3
2
1
2
1 1
070 cm , H-NMR (CDCl ) d 3.58 (s, 3H, CH ), 7.94 (t, J ¼ 8.0 Hz, 1H,
3
3
Ar), 8.43 (d, J ¼ 8.2 Hz, 1H, Ar), 8.79 (d, J ¼ 8.0 Hz, 1H, Ar), 9.13
þ
(
d, J ¼ 2.2 Hz, 1H, Ar), 9.31 (d, J ¼ 2.2 Hz, 1H, Ar); MS (m/z) 256 (M ,
100), 210, 198, 182, 153, 125, 99, 75; anal. calcd for C H N O : N, 10.93;
C, 60.93; H, 3.12. Found: N, 10.88; C, 60.82; H, 3.12.
13 8 2 4
3
-Nitro-N-ethyl-1,8-naphthalimide 3b. 89%; yellow crystals; mp 231–
2
1
2
328C; IR (KBr) 3383, 3051, 2986, 1697, 1655, 1624, 1540, 1335, 1080 cm
,
1
H-NMR (DMSO-d ) d 3.64 (br s, 2H), 4.14 (t, J ¼ 5.5 Hz, 2H), 4.8 (br s, 1H),
6
8
.02 (t, J ¼ 8.3 Hz, 1H, Ar), 8.63 (d, J ¼ 7.2 Hz, 1H, Ar), 8.73 (d, J ¼ 8.4 Hz,
1
H, Ar), 8.91 (d, J ¼ 2.0 Hz, 1H, Ar), 9.43 (d, J ¼ 2.3 Hz, 1H, Ar);
MS (m/z) 255, 243 (100), 225, 197, 171, 126, 75, 32; anal. calcd for
C H N O : N, 10.37; C, 62.22; H, 3.70. Found: N, 10.45; C, 60.31;
1
4 10 2 4
H, 3.76.
-Nitro-N-propyl-1,8-naphthalimide 3c. 83%; yellow crystals; mp
66–1678C; IR (KBr) 3087, 2959, 2871, 1702, 1660, 1542, 1351, 1243,
3
1
1
2
1 1
085 cm , H-NMR (DMSO-d ) d 0.925 (t, 3H, CH ), 1.65 (sextet, 2H,
6
3
CH ), 4.0 (t, 2H, CH ), 8.0 (t, J ¼ 8.0 Hz, 1H, Ar), 8.61 (d, J ¼ 7.1 Hz, 1H,
2
2
Ar), 8.64 (d, J ¼ 7.2 Hz, 1H, Ar), 8.91 (d, J ¼ 2.3 Hz, 1H, Ar), 9.41
þ
(
d, J ¼ 2.3 Hz, 1H, Ar); MS (m/z) 284 (100, M ); 243, 209, 179, 153, 126,
7
5, 41; anal. calcd for C H N O : N, 9.85; C, 63.38; H, 4.22. Found: N,
15 12 2 4
9.78; C, 63.48; H, 4.17.

ORDER
REPRINTS
Synthesis of N-Alkyl-1,8-naphthalimides
1997
3
-Nitro-N-butyl-1,8-naphthalimide 3d. 71%; yellow crystals; mp
[
27]
9
1
1
7.5–988C (literature
¼ 98–98.58C); IR (KBr) 3082, 2956, 1706, 1663,
3 3
21 1
595, 1545, 1348, 1234, 1087 cm , H-NMR (CDCl ) d 0.92 (t, 3H, CH ),
.57 (sextet, 2H, CH ), 1.72 (quintet, 2H, CH ), 4.18 (t, 2H, CH ), 7.92
2
2
2
(
t, J ¼ 7.24 Hz, 1H, Ar), 8.39 (d, J ¼ 8.2 Hz, 1H, Ar), 8.74 (d, J ¼ 7.2 Hz,
1
H, Ar), 9.11 (d, J ¼ 2.4 Hz, 1H, Ar), 9.28 (d, J ¼ 2.4 Hz, 1H, Ar); MS (m/
þ
z) 298 (M , 100), 243, 225, 209, 179, 151, 126, 75; anal. calcd for
C H N O : N, 9.39; C, 64.43; H, 4.69. Found: N, 9.38; C, 64.53; H, 4.60.
1
6 14 2 4
Method B (For Homogeneous Solution)
To a solution of potassium 4-sulfonic-1,8-naphthalic anhydride (1 mmol) in
0mL of distilled water in a 125-mL Erlenmeyer flask was added 10mmol of
5
the primary amine. The solution was sonicated using ultrasonic cleaning baths
with 150 W/25kHz or 50W/40kHz of power and frequency, respectively.
The temperature was maintained between 22 and 258C. After the reaction was
completed, the solvent was evaporated under vacuum and the crude product
washed with diethyl ether. The products were dried in a vacuum oven.
4
-Sulfonic-N-methyl-1,8-naphthalimide acid 4a. 88%; yellow needles;
2
1
IR (KBr) 3094, 2960, 2857, 1693, 1639, 1589, 1349, 1231, 1160, 1067 cm ,
1
H-NMR (CDCl ) d 2.88 (s, 3H, CH ), 7.35 (t, 1H, Ar), 7.68–7.80 (m, 3H,
3
3
Ar), 8.39 (d, 1H, Ar).
4-Sulfonic-N-butyl-1,8-naphthalimide acid 4b. 85%; yellow needles;
IR (KBr) 3092, 2956, 2857, 1707, 1652, 1587, 1348, 1225, 1160,
2
1 1
1
077 cm , H-NMR (CDCl ) d 0.98 (t, 3H, CH ), 1.55 (sextet, 2H, CH ),
3 3 2
1
.70 (quintet, 2H, CH ), 4.21 (t, 2H, CH ), 7.65 (t, 1H, Ar), 8.01–8.21
2
2
(
m, 3H, Ar), 8.69 (d, 1H, Ar).
4
-Butyl-N-butyl-1,8-naphthalimide 4c. 93%; yellow crystals; mp 125–
[
20]
1
268C (literature
¼ 127–1288C); IR (KBr) 3346, 2956, 1701, 1658, 1589,
3 3
2
201, 1084 cm , H-NMR (CDCl ) d 0.93–1.06 (m, 6H, 2CH ), 1.34–1.87
1
1
1
(
m, 8H, 4CH ), 3.17 (q, 2H, CH ), 4.16 (t, 2H, CH ), 5.18–5.25 (br s, 1H,
2 2 2
NH), 6.72 (d, J ¼ 8.2 Hz, 1H, Ar), 7.67 (t, J ¼ 8.4 Hz, 1H, Ar), 8.06
(
Ar); MS (m/z) 324 (M ), 307, 271, 268, 225, 207, 182 (100), 154; anal. calcd
d, J ¼ 7.3 Hz, 1H, Ar), 8.46 (d, J ¼ 8.4 Hz, 1H, Ar), 8.57 (d, J ¼ 7.3 Hz, 1H,
þ
for C H N O : N, 8.64; C, 70.07; H, 7.40. Found: N, 8.62; C, 70.05; H, 7.25.
16 14 2 4
ACKNOWLEDGMENTS
The authors thank FAPESP for providing financial support, CNPq and
CAPES for a scholarship to ERT. The authors thank Dr. Frank H. Quina
(
IQ–USP) for useful discussions.

ORDER
REPRINTS
1
998
Triboni et al.
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Received in the USA October 2, 2003

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