Studies on the Lossen-type rearrangement of N-(3-phenylpropionyloxy) phthalimide and N-tosyloxy derivatives with several nucleophiles

Article abstract of DOI:10.1016/j.tet.2010.01.074

The reaction of N-(3-phenylpropionyloxy)phthalimide (1a) and N-tosyloxy (5a,b) derivatives with nucleophiles was examined and found to give the products via Lossen-type rearrangement. In order to obtain the scope of this reaction mechanism, further studies the reaction of several N-sulfonyloxyimide derivatives with various nucleophiles under similar conditions were carried out and found to afford the corresponding same types of products in high yields.

Full text of DOI:10.1016/j.tet.2010.01.074

Tetrahedron 66 (2010) 2132–2140
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Studies on the Lossen-type rearrangement of N-(3-phenylpropionyloxy)
phthalimide and N-tosyloxy derivatives with several nucleophiles
*
Md. Chanmiya Sheikh , Shunsuke Takagi, Asako Ogasawara, Masayuki Ohira, Ryuta Miyatake,
Hitoshi Abe, Toshiaki Yoshimura, Hiroyuki Morita
Department of Applied Chemistry, Faculty of Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of N-(3-phenylpropionyloxy)phthalimide (1a) and N-tosyloxy (5a,b) derivatives with nu-
cleophiles was examined and found to give the products via Lossen-type rearrangement. In order to
obtain the scope of this reaction mechanism, further studies the reaction of several N-sulfonyloxyimide
derivatives with various nucleophiles under similar conditions were carried out and found to afford the
corresponding same types of products in high yields.
Received 13 November 2009
Received in revised form
18 January 2010
Accepted 20 January 2010
Available online 28 January 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Lossen rearrangement
Cross-linking reagent
Phthalimide
Active ester
1. Introduction
phenylpropionyloxy)benzothiazole
(1c),
and
N-(3-phenyl-
propionyl)benzotriazole (1d).5,6 However, in the reaction of 1b, 1c or
1d with BnOH, 3-phenylpropionic acid benzyl ester (2a) was
obtained as a sole product and in the case of 1a, we found un-
expectedly the formation of 2-benzyloxycarbonyl-N-(benzylox-
ycarbonyl)aniline (3a) besides the desired normal product 2a.7 To
study the scope and limitations of the reactions, we also prepared N-
sulfonyloxyimide derivatives and studied their reactions toward
several nucleophiles. Fahmy et al.8a reported the Lossen-type rear-
rangement product in N-(arysulfonyloxy)phthalimides using only
base catalyzed aromatic amines. However, these reaction systems
have not been applied to other organic reactions. Herein, we report
the full details in the reaction of 1a and N-sulfonyloxyimide de-
rivatives toward the various nucleophiles with mechanistic studies.
It is well known that hetero-functional bi-dentate cross-linking
reagents such as DSG (disuccimidyl glutarate), MBS (m-malei-mid-
obenzoyl-N-hydoxysuccinimide) and their related modified linkers
are useful in the area of chemical conjugation of particular bi-
ologically active molecules.1,2 Recently, by using MBS linker we have
succeeded in synthesizing the particular antigen bearing oxidized
cholesterol moiety by introducing SH group in the cholesterol
framework.3 While seeking more convenient and shorter synthetic
route,wehavefinallyusedthestepwiseapproach, however, wecould
not find the good conditions to obtain the target molecules.4 Under
these backgrounds, we strongly thought that the new type of non-
symmetrical cross-linking reagents bearing different bi-dentate re-
activities should be realized. Recently, we have succeeded to syn-
thesize the new non-symmetrical bi-dentate cross-linking reagents
having two different reactivities toward various nucleophilic groups
anddemonstratedtheirusefulnessforpreparationofpre-antigen.5 In
the course of these syntheses, it is necessary and important to de-
termine the reactivitiesof the ‘active ester’ groups toward thevarious
nucleophiles. Therefore, at first we have determined the reactivity
difference of several so-called ‘activated carbonyl’ groups using
the model compounds i.e. N-(3-phenylpropionyloxy)phthalimide
2. Results and discussion
2.1. Reaction of 1a with benzyl alcohol in the presence of
various bases
The active ester 1a was prepared by the following procedure,
which was reported previously.5 In our initial experiments, we
studied the reaction of 1a with BnOH in the presence of various
bases in CH2Cl2 at room temperature under N2 and the corre-
sponding ester 2a was obtained as a sole product and unexpectedly
we found the formation of 3a in very low yield. The results are
summarized in Table 1.
(1a),
N-(3-phenylpro-pio-nyloxy)benzotriazole
(1b),
N-(3-
* Corresponding author.
E-mail address: chansheikh@yahoo.com (M. C. Sheikh).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.074

Md. Chanmiya Sheikh et al. / Tetrahedron 66 (2010) 2132–2140
2133
Table 1
Table 3
Reaction of 1a with BnOH in the presence of various bases
Reaction of 1a, 5a or 5b with several hydroxyl compounds in the presence of DBU
O
O
O
ROH, DBU
O
BnOH, base
2b-d
+
3b-d
+
4b-d
N OZ
Ph
O N
Ph
OBn
O
CH Cl , rt, N
2
2
2
O
CH Cl , rt, N
2
2
2
O
1a
2a
BnO
Z = -CO(CH ) Ph (1a), -SO C H Me (5a),
2 2 2 6 4
-SO C H Me (5b)
O
2
6
2
3
BnO
+
+
Entry Compound ROH (2.0 equiv) Time
Producta (% yield)
2b–d 3b–d
HN
BnO
3a
H N
2
O
4b–d
4a
Producta (% yield)
1
2
3
4
5
1a
1a
1a
5a
5b
3 h
76 (2b) 13 (3b) 4 (4b)
70 (2b) 22 (3b) 8 (4b)
67 (2b) 23 (3b) 9 (4b)
15 h
24 h
10 min 0 (2b)
10 min 0 (2b)
CH3
Ph OH
Entry
BnOH (equiv)
Base
Time (h)
96 (3b) trace (4b)
95 (3b) trace (4b)
2a
3a
4a
1
2
3
4
2.0
2.0
2.0
2.0
4-DMAP
Et3N
24
40
40
40
82
47
53
46
5
7
19
27
0
0
18
11
6
7
8
9
1a
1a
1a
5a
5b
3 h
73 (2c) 12 (3c) 2 (4c)
69 (2c) 19 (3c) 4 (4c)
63 (2c) 23 (3c) 5 (4c)
DBN
DBU
15 h
24 h
10 min 0 (2c)
10 min 0 (2c)
Ph
OH
Ph
95 (3c) trace (4c)
93 (3c) trace (4c)
a
Yields were not optimized.
10
11
12
13
14
15
1a
1a
1a
5a
5b
PhOH
3 h
15 h
24 h
10 min 0 (2d)
10 min 0 (2d)
78 (2d) 4 (3d)
76 (2d) 6 (3d)
75 (2d) 7 (3d)
2(4d)
3(4d)
4(4d)
As shown in Table 1, when the reaction was performed using,
4-DMAP or Et3N as the base (entries 1,2), the yields of the side
products, 3a and 2-aminobenzoic acid benzyl ester (4a) were low.
In contrast, higher yields of 3a and 4a were obtained when strong
and more hindered base such as DBU or DBN was used (entries 3,4).
About the products formation, we presumed that the reaction
proceeded via the Lossen-type rearrangement.8,9
95 (3d) trace (4d)
93 (3d) trace (4d)
a
Yields were not optimized.
As shown in Table 3, the yield of the rearranged products, i.e.
2-benzyloxycarbonylamino benzoic acid 1-methylbenzyl ester (3b),
2-benzyloxycarbonylamino benzoic acid diphenylmethyl ester (3c),
and 2-benzyloxycarbonylamino benzoic acid phenyl ester (3d)13 was
greatly increased toward all the hydroxyl compounds, i.e. Bn(Me)OH,
Bn(Ph)OH, and PhOH (entries, 1–3, 6–8, 11–13). In addition, the
products, 2-benzyloxycarbonylamino benzoic acid 1-methylbenzyl
ester (4b),14 2-aminobenzoic acid diphenylmethyl ester (4c),15 and 2-
aminobenzoic acid phenyl ester (4d)16 were also generated. We then
examined the reaction of corresponding tosyl ester (5a,b) was also
carried out under similar conditions and the best results were
obtained in shorter time (entries, 4,5, 9,10, 14,15). The results clearly
indicate that in the cases of the stronger base and better leaving
group the Lossen-type rearrangement products 3a–d are favored
and increased. The mechanisms were considered for the formation
of 3a–d as shown in Scheme 1. However, the mechanisms for the
formation of 4a–d were unclear yet.
2.2. Reaction of 1a and N-tosyloxy derivatives (5a,b) with
various hydroxyl compounds in the presence of DBU
In order to obtain additional examples, we studied the reaction
of the corresponding tosyl ester,10,11 N-tosyloxyphthalimide (5a),
and N-(2-mesitylenesulfonyloxy)phthalimide (5b) having a better
leaving group than 1a (i.e., 3-phenylpropionate anion) with BnOH
in the presence of DBU in CH2Cl2 at room temperature under N2 and
resulted in the greatly improved yield of the Lossen-type rear-
rangement product 3a. The results are listed in Table 2.
Table 2
Reaction of 1a, 5a or 5b with BnOH in the presence of DBU
O
O
O
BnOH, DBU
O
RO
OR
N
ROH, DBU
2a
+
3a
+
4a
N OZ
O
N
O
Ph
1a
CH Cl , rt, N
2
2
2
O
Ph
O
O
O
Z = -CO(CH ) Ph (1a), -SO C H Me (5a),
2 2
2 6 4
O
O
N
O
-SO C H Me (5b)
nitrene mechanism
or
concerted mechanism
2
6
2
3
ROH
RO
H N
OR
C
RO
HN
RO
2
Entry
Compound
BnOH (equiv)
Time (h)
Producta (% yield)
O
O
3a-d
-Lossen rearrangement-
4a-d
2a
3a
4a
1
2
3
4
5
6
7
1a
1a
1a
5a
5a
5b
5b
2.0
2.0
3.0
2.0
2.0
2.0
2.0
3
12
24
0.5
24
0.5
24
68
62
48
0
0
0
11
21
24
91
93
90
93
6
9
20
trace
trace
trace
trace
Scheme 1. Plausible mechanism for the formation of 3a–d.
2.3. Reaction of 1a and N-tosyloxy derivatives (5a,b) with
benzylamine in the presence of DBU
0
We studied the reaction of 1a and 5a,b with BnNH2 having strong
nucleophilicity, compared to BnOH, tend to attack the carbonyl
carbon of ester group under similar conditions.
a
Yields were not optimized.
As can we see in from Table 2, the rearranged product, i.e. 3a was
greatly increased and in addition, the product 4a12 was also in-
creased (entries 2,3). Further, the reaction of 5a,b revealed to afford
the product 3a in excellent yield (entries 4–7). For careful inspection
of the products, next we studied the reaction toward several
hydroxyl compounds {i.e., Bn(Me)OH, Bn(Ph)OH, and PhOH} under
similar conditions. The results are shown in Table 3.
The results are summarized in Table 4. In this case the side
products, N-benzyl-2-(3-benzylureido)benzamide (3e),17 N-ben-
zylphthalimide (6),18 and N,N-dibenzylphthalimide (7)19 were
obtained when the reaction time was very short but yield was not
high. The products 3e and 7 were increased and to give relatively
reduced yield of 6 after passing the reaction time. The results are
shown in Table 4.

2134
Md. Chanmiya Sheikh et al. / Tetrahedron 66 (2010) 2132–2140
Table 4
For the mechanism of these side products, the formation of 7 was
proceeded by the attack of BnNH2 to the carbonyl carbon of phtha-
limidoyl group to generate nitrene 8 followed by Lossen-type rear-
rangement, which is quickly undergoes a concerted rearrangement
to the 6 and finally, 7 was formed by the reaction of BnNH2.
Reaction of 1a, 5a or 5b with BnNH2 in the presence of DBU
O
O
O
BnNH , DBU
BnHN
2
+
NHBn
Ph
N OZ
HN
CH Cl , rt, N
2
2
2
BnHN
O
O
2e
3e
Z = -CO(CH ) Ph (1a),
2 2
O
2.4. Reaction of 1,8-naphthalene derivatives (9a,b) with
several nucleophiles in the presence of DBU
O
-SO C H Me (5a),
-SO
2
2
6 4
C H Me (5b)
6
BnHN
Ph
+
N
O
2
3
+
BnHN
We prepared 1,8-naphthalene derivatives20 i.e. 1,8-naphthali-
midoyloxy tosylate (9a) by the reaction of N-hydroxy1,8-naphtha
limide with tosyl chloride and N-mesitylenesulfonyl-1,8-naph-
thalimide (9b) by the reaction of 2-mesitylenesulfonyl chloride
with N-hydroxy-1,8-napthalimide and examined their reaction
with BnOH or BnSH in the presence of DBU in CH2Cl2 at room
temperature under N2. In this case, the corresponding product
1-(benzyloxycarbonyl)benzo[c,d]indol-2-one (10a) or 1-(benzylth-
iocarbonyl)benzo[c,d]indol-2-one (10b) was obtained via Lossen-
type rearrangement together with benzo[c,d]indol-2-one (11).21
The results are summarized in Table 6.
O
6
7
Entry Compound BnNH2 (equiv) DBU (equiv) Time
Producta (% yield)
2e 3e
6
7
1
2
3
4
5
6
7
1a
1a
1a
5a
5a
5b
5b
2.0
2.0
2.0
1.3
2.0
1.3
2.0
2.0
2.0
2.0
1.3
2.0
1.3
2.0
3 h
12 h
24 h
30 min
10 min
30 min
10 min
58 Trace 36
6
9
55
54
0
0
0
2
3
64
98
62
94
32
19 13
0
0
0
0
trace
trace
trace
trace
0
a
Yields were not optimized.
Table 6
Reaction of 1,8-naphthalimide derivative 9a or 9b with various nucleophiles
O
NH
O
N OZ
O
O
As shown in Table 4 in the reaction of 1a we found unexpectedly
NuH, DBU
CH Cl , rt, N
2
O
+
N
the formation of 6 and 7 in low yields and 7 was obtained more
than that of 6 after prolonged reaction time. In order to elucidate
the possible mechanism, we carried out the reaction of 6 with
BnNH2 in the presence of DBU in CH2Cl2 at room temperature
under N2. The results are summarized in Table 5.
2
2
Nu
Z = -SO C H Me (9a),
2
6 4
10a-b
11
-SO C H Me (9b)
2
6
2
3
Entry Compound NuH NuH (equiv) DBU (equiv) Time (h) Producta (% yield)
10a,b 11
Table 5
1
2
3
4
9a
9a
9b
9b
BnOH 1.5
2.1
1.5
2.1
1.5
2.1
3
2
3
2
49 (10a) trace
60 (10a) 15
40 (10a) trace
Reaction of 6 with BnNH2 in the presence of DBU
1.5
2.1
O
O
BnNH , DBU
54 (10a)
9
2
BnHN
BnHN
7
Ph
N
5
6
7
8
9a
9a
9b
9b
BnSH 1.5
2.1
1.5
2.1
1.5
2.1
3
2
3
2
45 (10b)
58 (10b)
41 (10b)
51 (10b)
0
0
0
0
CH Cl , rt, N
2
2
2
O
O
6
1.5
2.1
Entry BnNH2 (equiv) DBU (equiv) Time (h) 7a (% yield) 6b (% recover)
a
Yields were not optimized.
1
2
3
4
1.2
2.0
2.0
2.0
1.2
2.0
2.0
2.0
30
1
3
12
19
53
79
58
80
46
20
Therefore, the most probable mechanism for this reaction is
illustrated in Scheme 3.
41
a
Yields were not optimized.
Compound 6 was recovered.
b
O
O
O
Nu
OTs
N
Nu
N
Nu
OTs
N
O
O
O
As shown in Table 5 the reactant 6 was decreased and the cor-
responding 7 was increased after passing the reaction time.
Therefore, the most probable mechanism for the formation of 7 is
illustrated in Scheme 2.
9a-b
12
13
O
Lossen
O
Nu
Nu
N C O
rearrangement
N
O
O
O
O
O
Ph NH
H
N
2
Ph
O
Ph
O
Nu
N
H
isocyanate
N O
Ph
H
10a-b
14
O
N
NH
O
O
O
O
Scheme 3. Possible routes for 10a,b from the reactions of 9a,b with BnOH and BnSH.
8
1a
Ph
Ph
H N Ph
2
O
O
O
N
2.5. X-ray crystallographic analysis of 10a and 10b
O
H
N
Ph
NH
Ph
NHBn
NHBn
N
Ph
H
Since X-ray crystal structures of 10a, and 10b are not available,
hence, the structure of 10a, and 10b were also confirmed by
single crystal X-ray crystallographic analysis. An ORTEP drawing
and some selected bond lengths and angles are listed in Figures 1
and 2.
N
O
O
Ph
O
O
H
O
O
6
7
Ph
Scheme 2. Possible routes for the formation of 7 from the reaction of 1a with BnNH2.

Md. Chanmiya Sheikh et al. / Tetrahedron 66 (2010) 2132–2140
2135
We then investigated the reaction of 9a with BnNH2 under
similar conditions. The results are summarized in Table 7.
Table 7
Reaction of 1,8-naphthalimide derivative 9a with BnNH2
O
O
Bn N
O
O
N
BnNH , DBU
2
BnHN
O
9a
+
+
CH Cl , rt, N
2
2
2
HN
NHBn
BnHN
O
10c
15
16
Entry
BnNH2 (equiv)
DBU (equiv)
Time (h)
Product (% yield)a
10c
15
16
1
2
1.5
2.1
1.5
2.1
3
2
0
0
45
65
5
9
a
Yields were not optimized.
The side products N-benzyl-1,8-phthalimide (15),22 and 1-ben-
zylaminocarbonylamino naphthalic acid benzylamide (16) were
obtained when the reaction time was very short. The probable
mechanism for these side products, the nucleophile will attack the
carbonyl carbon of phthalimidoyl group instead of the ester group
to produce the unexpected products Scheme 4.
O
O
O
BnNH
2
OTs
NHBn
HN
Bn
O
N
OTs
N
NH OTs
2
+
O
O
9a
15
17
18
Scheme 4. Possible routes for the formation of 15 from the reaction of 9a with BnNH2.
Figure 1. Crystal structure of compound 10a. Selected bond lengths (Å) and bond angles
(ꢀ): N(1)–C(1), 1.453(3); N(1)–C(9), 1.428(3); N(1)–C(12), 1.393(3); C(12)–O(2), 1.199(3);
C(12)–O(3), 1.326(3); C(1)–N(1)–C(9), 109.6(2); C(1)–N(1)–C(12), 127.6(2); C(9)–N(1)–
C(12), 122.6(2); N(1)–C(12)–O(2), 122.3(2); N(1)–C(12)–O(3), 11.6(2); O(2)–C(12)–O(3),
126.0(3).
2.6. Reaction of aliphatic dicarboxylic acid derivatives (19a,b)
with several nucleophiles in the presence of DBU
Interesting sequence involving in the reaction of the aliphatic
dicarboxylic acid imide derivatives.23 Therefore, we prepared
N-succinimidoyloxytosylate (19a), and N-mesitylenesulfonyloxy-
succinimide (19b), and examined their reaction with several nucle-
ophiles under similar conditions. Expectedly, the corresponding
amino
acid
derivatives,
benzyl
3-(bezylox-
ycarbonylamino)propionate (20a),24 and N-{2 (benzylaminocarbo-
nyl)ethyl}-N0-benzyl urea (20b)25 were obtained in moderate to high
yields. Experimental results of 19a differ little from that of 19b due to
their different leaving ability of leaving group. The results are sum-
marized in Table 8.
Table 8
Reaction of succinimide derivatives 19a or 19b with various nucleophiles
O
O
O
O
NuH, DBU
CH Cl , rt, N 2 h
+
N OZ
N
Nu
N
H
Nu
XR
2
2
2,
O
O
Z = -SO C H Me (19a),
2
6 4
20a-b
21a-b
-SO C H Me (19b)
2
6
2
3
Entry Compound NuH NuH (equiv) DBU (equiv) Producta (% yield)
20a,b
21a,b
1
2
3
4
BnOH
19a
19a
19b
19b
1.5
2.1
1.5
2.1
1.5
2.1
1.5
2.1
61 (20a)
75 (20a)
57 (20a)
68 (20a)
0 (21a)
0 (21a)
0 (21a)
0 (21a)
Figure 2. Crystal structure of compound 10b. Selected bond lengths (Å) and bond
angles (ꢀ): N(1)–C(1), 1.4089(9); N(1)–C(11), 1.415(10); N(1)–C(12), 1.33(1); C(12)–O(2),
1.227(10); C(12)–S(1), 1.763(6); C(1)–N(1)–C(11), 109.5(6); C(1)–N(1)–C(12), 122.9(6);
C(11)–N(1)–C(12), 126.9(6); N(1)–C(12)–O(2), 124.2(6); N(1)–C(12)–S(1), 116.8(6);
O(2)–C(12)–S(1), 119.0(7).
5
6
7
8
BnNH2
19a
19a
19b
19b
1.5
2.1
1.5
2.1
1.5
2.1
1.5
2.1
44 (20b) 0 (21b)
59 (20b) 0 (21b)
41 (20b) 0 (21b)
52 (20b) 0 (21b)
a
Yields were not optimized.

2136
Md. Chanmiya Sheikh et al. / Tetrahedron 66 (2010) 2132–2140
Compounds 20a, and 20b are
b-amino acid derivatives and will
derivatives 9a,b, and also aliphatic dicarboxylic acid derivatives
be possible to employ this method for preparing
b
-amino acid
19a,b and 22, and examined their reactions with nucleophiles under
the similar conditions and expectedly obtained the Lossen-type
rearranged product, i.e. 10a,b, 20a,b, 23a,b, and 24c–d in excellent
yields, respectively. These new finding could be applied to the syn-
thetic application of amino acid derivatives under mild reaction
conditions with good to excellent yields. Regarding operational
simplicity, mild reaction conditions, and cost, this method offers
significant advantages over previously reported methods.29
derivatives. Also we prepared the six membered cyclic compound,
N-(p-toluenesulfoxy)glutamide (22) by the reaction of N-hydrox-
ysuccinimide with tosyl chloride and studied their reaction with
several nucleophiles under similar conditions. The results are sum-
marized in Table 9. As shown in Table in the case of BnOH and BnNH2
the corresponding amino acid derivatives, benzyl 3-(benzylox-
ycarbonylamino)butanoate (23a),26 and N-{2 (benzylaminocarbo-
nyl)propyl}-N0-benzyl urea (23b) (entries 1–4) were obtained in
moderate to high yields. In contrast, when the reaction was carried
out with phenol or p-cresol, the corresponding products,
4. Experimental section
4.1. General
N-(phenyloxycarbonyl)pyrrolidine-2-one (24c)27 or N-(methyl-
28
phenyloxycarbonyl)pyrrolidine-2-one (24d)
(entries 5,6) was
obtained in good yields.
All the melting points were uncorrected using micro melting
point apparatus. 1H NMR (400 MHz) and 13C NMR (100 MHz)
spectra were recorded in CDCl3 using TMS as an internal standard.
All the reactions were monitored with TLC and the products were
separated by column chromatography using silica gel 60 and by
preparative layer chromatography using silica gel 60 PF254 with
UV or PMA and DNP detection. Mass spectra were obtained on
a JEOL-JMS-D300 mass spectrometer. The elemental analyses
were performed at Micro Analytical Laboratory of the Department
of Material Systems Engineering and Life Science, University of
Toyama.
Table 9
Reaction of glutamide derivative 22 with various nucleophiles
O
O
O
H
N
O
NuH, DBU
Nu
N
N OTs
O
Nu
+
Nu
24a-d
Time (h) Producta (% yield)
CH Cl , rt, N
2
O
2
2
23a-d
22
Entry NuH
NuH
DBU
(equiv) (equiv)
23a–d
24a–d
1
2
BnOH
BnNH2
PhOH
1.5
2.1
1.5
2.1
2
2
68 (23a)
100 (23a) 0 (24a)
0 (24a)
4.2. Preparation of N-(3-phenylpropionyloxy)phthalimide 1a
3
4
1.5
2.1
1.5
2.1
2
2
52 (23b)
81 (23b)
0 (24b)
0 (24b)
DCC (1786.8 mg, 8.66 mmol) was added to a stirred solution of
hydrocinnamic acid (500.0 mg, 6.66 mmol) and N-hydroxyphtha-
limide (1412.2 mg, 8.66 mmol) in CH2Cl2 at 0 ꢀC and stirred for 3 h.
The precipitate was filtered and washed with CH2Cl2. Purification
by preparative TLC yielded N-(3-phenylpropionyl-oxy)phthalimide
1a (902.2 mg, 92%) as a colorless solid; mp 84.2–84.5 ꢀC (from
5
6
2.1
2.1
2.1
2.5
2.5
0 (23c)
0 (23d)
59 (24c)
56 (24d)
p-Me-C6H4OH 2.1
a
Yields were not optimized.
Therefore, it is expected that many kinds of amino acid de-
rivatives easily attained by using the new methods described here
and we have considered the reaction mechanism in Scheme 5.
CH2Cl2–hexane); 1H NMR (CDCl3, 400 MHz)
d 2.96–3.00 (m, 2H),
3.11 (t, J¼7.2 Hz, 2H), 7.23–7.27 (m, 3H), 7.31–7.35 (m, 2H),
7.77–7.81 (m, 2H), 7.86–7.91 (m, 2H); 13C NMR (CDCl3, 100 MHz)
O
O
O
S
O
O S
O
O
O
d
30.6, 32.7, 123.9, 126.7, 128.3, 128.7, 128.9, 134.8, 139.2, 161.9,
N
N
N O S
Nu
N
168.9; IR (KBr) 1789, 1740 cmꢁ1. Anal. Calcd for C17H13NO4: C, 69.15;
H, 4.44; N, 4.74. Found: C, 69.14; H, 4.52; N, 4.69.
n
n
n
O
O
Nu
O
Nu
O
O
O
n = 1 (19a-b), n = 2 (22)
Lossen
rearrangement
25
26
O
O
S
O
O
O
O
N
Nu
C
O
4.3. General procedure for the preparation of 5a,b
(5a as an example)
n
Nu
N
H
Nu
Nu
n
n
O
Nu
bridge anion
isocyanate
27
20a-b (n = 1),
23a-b (n = 2)
Pyridine (2 mL) was added to a stirred solution of N-hydroxy-
phthalimide (1000.0 mg, 6.13 mmol) and tosyl chloride (1284.9 mg,
6.74 mmol) in CH2Cl2 (20 mL) at room temperature under N2 and
stirred for 1 h. The crude product was washed with pure water
followed by purification by silica gel chromatography (CH2Cl2) to
afford N-tosyloxyphthalimide 5a (1792.0 mg, 92%) as a colorless
solid; mp 161.0–161.5 ꢀC (from CH2Cl2–hexane); 1H NMR (CDCl3,
Scheme 5. Probable mechanism for the formation of amino acid derivatives (20a,b
and 23a,b).
The unexpected formation of 20a,b (n¼1) or 23a,b (n¼2) pro-
ceeded by the attack of the nucleophile to the carbonyl carbon of
imidoyl group 19a,b or 22 to generate nitrene 26, which is quite
unstable and quickly undergoes a concerted rearrangement to the
isocyanate 27 via bridged anion, and finally, 20a,b or 23a,b were
formed by the reaction of BnOH or BnNH2.
400 MHz)
d 2.50 (s, 3H), 7.40–7.42 (m, 2H), 7.78–7.83 (m, 2H),
7.84–7.89 (m, 2H), 7.95–7.97 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d
21.9, 124.3, 128.6, 129.6, 130.1, 130.6, 135.1, 147.0, 161.3; IR (KBr)
1796, 1746 cmꢁ1. Anal. Calcd for C15H11NO5S: C, 56.78; H, 3.49; N,
4.41. Found: C, 56.81; H, 3.59; N, 4.30.
3. Conclusion
4.3.1. N-(2-Mesitylenesulfonyloxy)phthalimide 5b. Yield 93%; mp
In conclusion, we have described the reaction of 1a and N-tosy-
loxy derivatives 5a,b with several nucleophiles in the presence of
DBU under similar reaction conditions. In view of the results of the
intensive mechanistic studies, it indicates clearly that the products
3a–e and 4a–d were formed via the Lossen-type rearrangement. In
order to probe the scope further, we prepared 1,8-naphthalene
174.4–175.0 ꢀC (colorless solid from CH2Cl2–hexane); 1H NMR
(CDCl3, 400 MHz)
d
2.35 (s, 3H), 2.69 (s, 6H), 7.03 (s, 2H), 7.77–7.81
21.3, 23.0,
(m, 2H), 7.83–7.86 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d
124.2, 128.5, 129.4, 131.9, 135.0, 141.6, 145.2, 161.5; IR (KBr) 1798,
1752 cmꢁ1. Anal. Calcd for C17H15NO5S: C, 59.12; H, 4.38; N, 4.06.
Found: C, 59.15; H, 4.40; N, 4.09.

Md. Chanmiya Sheikh et al. / Tetrahedron 66 (2010) 2132–2140
2137
4.4. General procedure for the preparation of 2a–e from 1a
and 5a,b (2a as an example)
128.5, 128.6, 130.9, 134.7, 135.4, 136.1, 141.8, 153.4, 167.7; IR (KBr) 1738,
1685 cmꢁ1. Anal. Calcd for C22H19NO4: C, 73.12; H, 5.30; N, 3.88.
Found: C, 73.37; H, 5.30; N, 3.97.
DBU (50.5
mL, 0.34 mmol) was added to a stirred solution of 1a
(50.0 mg, 0.17 mmol) and benzyl alcohol (35.0
m
L, 0.34 mmol) in
4.5.1. 2-Benzyloxycarbonylamino benzoic acid 1-methylbenzyl ester
CH2Cl2 (2 mL) at room temperature under N2 and stirred for 3 h.
Then, the reaction mixture was neutralized by dil AcOH solution
and extracted with CH2Cl2. The organic layer was separated, suc-
cessively washed with water and brine, and dried over anhydrous
MgSO4. Removal of solvent in vacuum gave a colorless oil crude
product, which was purified by preparative TLC (CH2Cl2–hexane) to
give 3-phenylpropionic acid benzyl ester 2a (27.6 mg, 68%) as
3b. Colorless liquid; 1H NMR (CDCl3, 400 MHz)
d
1.46 (dd, J¼5.0,
6.6 Hz, 3H), 1.54 (dd, J¼3.4, 6.6 Hz, 3H), 5.76 (q, J¼6.6 Hz, 1H),
5.96–6.02 (m, 1H), 6.85–6.89 (m, 1H), 7.04–7.37 (m, 11H), 7.98 (dd,
J¼3.9, 7.8 Hz, 1H), 8.33 (d, J¼8.4 Hz, 1H), 10.45 (s, 1H); 13C NMR
(CDCl3, 100 MHz)
d 22.3, 22.4, 73.1, 73.3, 114.6, 114.6, 118.6, 118.7,
121.3, 125.8, 125.9, 127.7, 127.9, 128.4, 128.6, 130.8, 134.5, 141.7, 141.9,
152.7, 152.8, 167.1; IR (KBr) 1736, 1685 cmꢁ1. HRMS (EI) calcd for
C24H23NO4: 389.1627; found: m/z 389.1627.
a colorless liquid; 1H NMR (CDCl3, 400 MHz)
d
2.68 (t, J¼7.8 Hz, 2H),
2.97 (t, J¼8.0 Hz, 2H), 5.11 (s, 2H), 7.17–7.35 (m, 10H); 13C NMR
(CDCl3, 100 MHz)
d
30.9, 35.9, 66.2, 126.2, 128.2, 128.3, 128.5, 128.5,
4.5.2. 2-Benzyloxycarbonylamino benzoic acid diphenylmethyl ester
135.9, 140.4, 172.7; IR (NaCl disc) 1734 cmꢁ1. HRMS (EI) calcd for
3c. Mp 148.2–149 ꢀC (colorless solid from CH2Cl2–hexane); 1H
C16H16O2: 240.1150; found: m/z 240.1123.
NMR (CDCl3, 400 MHz) d 6.87 (s, 1H), 7.03–7.05 (m, 1H), 7.11 (s, 1H),
7.23–7.43 (m, 20H), 7.49–7.54 (m, 1H), 8.21 (dd, J¼2.0, 8.2 Hz, 1H),
4.4.1. 3-Phenylpropionic acid 1-methylbenzyl ester 2b. Colorless
8.46 (d, J¼8.4 Hz, 1H), 10.66 (s, 1H); 13C NMR (CDCl3, 100 MHz)
liquid; 1H NMR (CDCl3, 400 MHz)
d
1.55 (d, J¼6.8 Hz, 3H), 2.71
d 77.7, 77.8, 114.5, 118.9, 121.7, 127.0, 127.1, 127.9, 128.2, 128.5, 128.7,
(dt, J¼7.8, 8.2 Hz, 2H), 3.0 (t, J¼8.2 Hz, 2H), 5.94 (q, J¼6.4 Hz, 1H),
130.9, 134.8, 139.7, 140.2, 141.9, 152.7, 166.9; IR (KBr) 1729,
1695 cmꢁ1. HRMS (EI) calcd for C34H27NO4: 513.1940; found: m/z
513.1938.
7.22–7.29 (m, 3H), 7.30–7.41 (m, 7H); 13C NMR (CDCl3, 100 MHz)
d
22.1, 30.9, 36.1, 72.3, 126.0, 126.2, 127.8, 128.3, 128.4, 140.4, 141.9,
172.1; IR (NaCl disc) 1733 cmꢁ1. HRMS (EI) calcd for C17H18O2:
254.1307; found: m/z 254.1303.
4.5.3. 2-Benzyloxycarbonylamino benzoic acid phenyl ester 3d. Mp
84.5–87 ꢀC (colorless solid from CH2Cl2–hexane); 1H NMR (CDCl3,
4.4.2. 3-Phenylpropionic acid diphenyl-methyl ester 2c. Mp
400 MHz)
8.22 (dd, J¼1.6, 8.0 Hz,1H), 8.44 (dd, J¼0.4, 8.4 Hz,1H),10.57 (s,1H);
13C NMR (CDCl3, 100 MHz)
114.1, 119.1, 120.6, 121.6, 121.7, 122.2,
125.6, 126.2, 126.3, 129.3, 129.5, 131.4, 135.5, 142.0, 150.3, 150.5,
151.7, 167.0; IR (KBr) 1759, 1699 cmꢁ1
HRMS (EI) calcd for
C20H15NO4: 333.1001; found: m/z 333.0999.
d 7.05–7.34 (m, 7H), 7.35–7.40 (m, 2H), 7.52–7.57 (m, 1H),
50–51 ꢀC (colorless solid from AcOEt–hexane); 1H NMR (CDCl3,
400 MHz)
d
2.71–2.75 (m, 2H), 2.96 (t, J¼7.8 Hz, 2H), 6.89 (s, 1H),
d
7.10–7.20 (m, 3H), 7.22–7.31 (m, 12H); 13C NMR (CDCl3, 100 MHz)
d
30.9, 36.0, 76.9, 126.2, 127.1, 127.8, 128.3, 128.4, 128.5, 140.1, 140.3,
.
171.8; IR (KBr) 1734 cmꢁ1. HRMS (EI) calcd for C22H20O2: 316.1463;
found: m/z 316.1461.
4.5.4. N-Benzyl-2-(3-benzylureido)benzamide 3e. Mp 139–140 ꢀC
4.4.3. 3-Phenylpropionic acid phenyl ester 2d. Colorless liquid; 1H
(colorless solid from CH2Cl2–hexane); 1H NMR (CDCl3, 400 MHz)
NMR (CDCl3, 400 MHz)
d
2.87 (t, J¼7.6 Hz, 2H), 3.06 (t, J¼7.6 Hz,
d
4.44 (s, 2H), 4.54 (d, J¼5.6 Hz, 2H), 5.14 (s, 2H), 6.66 (s, 1H),
6.88–6.93 (m, 1H), 7.23–7.41 (m, 12H), 8.39–8.42 (m, 1H), 10.39 (s,
1H); 13C NMR (CDCl3, 100 MHz)
43.9, 44.4, 118.9, 120.8, 121.0,
2H), 6.98–7.01 (m, 2H), 7.17–7.36 (m, 8H); 13C NMR (CDCl3,
100 MHz)
d
30.9, 35.9, 121.5, 125.8, 126.4, 128.4, 128.6, 129.4, 140.1,
d
150.6, 171.4; IR (NaCl disc) 1759 cmꢁ1. HRMS (EI) calcd for
126.4, 127.4, 127.7, 128.6, 128.8, 132.6, 137.5, 141.1, 155.0, 169.3; IR
(KBr) 1665, 1629 cmꢁ1. HRMS (EI) calcd for C22H21N3O2: 359.1634;
found: m/z 359.1633.
C22H20O2: 226.0994; found: m/z 226.0990.
4.4.4. N-Benzyl-3-phenylpropionamide 2e. Mp 76.5–77.0 ꢀC (color-
less solid from CH2Cl2–hexane); 1H NMR (CDCl3, 400 MHz)
d
2.51 (t,
J¼7.6 Hz, 2H), 2.99 (t, J¼6.8 Hz, 2H), 4.39 (d, J¼6.0 Hz, 2H), 5.62 (s,
1H), 7.13–7.31 (m, 10H); 13C NMR (CDCl3, 100 MHz)
31.7, 38.5, 43.6,
4.6. General procedure for the preparation of 4a–e from 1a
and 5a,b (4a as an example)
d
126.2, 127.4, 127.7, 128.4, 128.5, 128.6, 138.1, 140.7, 171.8; IR (KBr)
1639 cmꢁ1. Anal. Calcd for C16H17NO: C, 80.30; H, 7.16; N, 5.85.
Found: C, 80.34; H, 7.16; N, 5.90.
DBU (50.5
m
L, 0.34 mmol) was added to a stirred solution of 1a
L, 0.34 mmol) in
(50.0 mg, 0.17 mmol) and benzyl alcohol (35.0
m
CH2Cl2 (2 mL) at room temperature under N2 and stirred for 40 h.
Then, the reaction mixture was neutralized by dil AcOH solution
and extracted with CH2Cl2. The organic layer was separated,
successively washed with water and brine, and dried over anhy-
drous MgSO4. Removal of solvent in vacuum gave a colorless oil
crude product, which was purified by preparative TLC (CH2Cl2–
hexane) to give 2-aminobenzoic acid benzyl ester 4a (4.6 mg, 11%)
4.5. General procedure for the preparation of 3a–e from 1a
and 5a,b (3a as an example)
A solution of DBU (76.3
mL, 0.51 mmol) was added to a stirred
solution of 1a (50.0 mg, 0.17 mmol) and benzyl alcohol (52.8
mL,
0.51 mmol) in CH2Cl2 (2 mL) at room temperature under N2 and
stirred for 24 h. Then, the reaction mixture was neutralized by dil
AcOH solution and extracted with CH2Cl2. The organic layer was
separated, successively washed with water and brine, and dried over
anhydrous MgSO4. Removal of solvent in vacuum gave a colorless oil
crude product, which was purified by preparative TLC (3:1 CH2Cl2–
hexane) to give 2-benzyloxycarbo-nyl-N-(benzyloxycarbonyl)aniline
3a (15.2 mg, 24%) as a colorless solid; mp 74.0–74.5 ꢀC (from CH2Cl2–
as a colorless liquid; 1H NMR (CDCl3, 400 MHz)
(s, 2H), 6.61–6.66 (m, 2H), 7.23–7.44 (m, 6H), 7.91 (dd, J¼2.0,
8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz)
65.9, 110.6, 116.3, 116.6,
127.9, 128.1, 128.5, 131.3, 134.2, 136.3, 150.6, 167.9; IR (KBr)
1689 cmꢁ1. HRMS (EI) calcd for C14H13NO2: 277.0946; found: m/z
277.0918.
d 5.32 (s, 2H), 5.73
d
4.6.1. 2-Aminobenzoic acid 1-methylbenzyl ester 4b. Colorless
hexane); 1H NMR (CDCl3, 400 MHz)
d
5.21 (s, 2H), 5.33 (s, 2H), 6.98–
liquid; 1H NMR (CDCl3, 400 MHz)
d
1.58 (d, J¼6.8, 3H), 5.63 (s, 2H),
7.02 (m, 1H), 7.29–7.43 (m, 10H), 7.49–7.54 (m, 1H), 8.04 (dd, J¼2.0,
6.01 (q, J¼6.5 Hz, 1H), 6.56–6.61 (m, 2H), 7.17–7.24 (m, 2H),
1.6 Hz, 1H), 8.46 (d, J¼8.4 Hz, 1H), 10.57 (s, 1H); 13C NMR (CDCl3,
7.27–7.31 (m, 2H), 7.35–7.37 (m, 2H), 7.89 (dd, J¼2.0, 8.2 Hz,1H); 13C
100 MHz)
d
66.9, 66.9, 114.5, 118.8, 121.6, 128.2, 128.2, 128.2, 128.4,
NMR (CDCl3, 100 MHz) d 22.6, 72.2, 111.0, 116.2, 116.6, 125.9, 127.7,

2138
Md. Chanmiya Sheikh et al. / Tetrahedron 66 (2010) 2132–2140
128.5, 131.2, 134.1, 142.1; IR (KBr) 1685 cmꢁ1. HRMS (EI) calcd for
C15H15NO2: 241.1103; found: m/z 241.1081.
4.10. General procedure for the preparation of 10a,b
(10a as an example)
4.6.2. 2-Aminobenzoic acid phenyl ester 4d. Mp 57–59 ꢀC (light
Benzyl alcohol (42.2 mL, 0.41 mmol) and DBU (61.0 mL,
yellow solid from CH2Cl2–hexane); 1H NMR (CDCl3, 400 MHz)
0.41 mmol) solution was added to a stirred solution of N-tosyloxy-
1,8-naphthalimide 9a (100.0 mg, 0.27 mmol) in CH2Cl2 (3 mL) and
stirred at room temperature under N2 for 3 h. Then, the reaction
mixture was neutralized by dil AcOH solution and extracted with
CH2Cl2 and H2O, dried over anhydrous MgSO4, and concentrated
under vacuum and the resulting residue was purified by flash
chromatography on silica gel using hexane–AcOEt to give 1-(ben-
zyloxycarbonyl)benzo[c,d]indol-2-one 10a (40.4 mg, 49%) as
a colorless solid; mp 120–121 ꢀC (from CH2Cl2–hexane); 1H NMR
d
5.70 (s, 2H), 6.63–6.67 (m, 2H), 7.09–7.13 (m, 2H), 7.18–7.29
(m, 2H), 7.33–7.39 (m, 2H), 8.02 (dd, J¼1.2, 8.4 Hz, 1H); 13C
NMR (CDCl3, 100 MHz)
d 116.4, 116.8, 121.9, 125.8, 129.5, 131.6,
134.8, 150.8, 151.0, 166.8, 166.8, 188.8; IR (KBr) 1689 cmꢁ1
.
HRMS (EI) calcd for C13H11NO2: 213.0790; found: m/z
213.0762.
4.7. N-Benzylphthalimide 6
(CDCl3, 400 MHz)
d 5.52 (s, 2H), 7.33–7.44 (m, 3H), 7.50–7.58
(m, 3H), 7.66 (d, J¼8.8 Hz, 1H), 7.71–7.76 (m, 1H), 7.80 (d, J¼7.6 Hz,
Mp 113.3–113.6 ꢀC (colorless solid from CH2Cl2–hexane); 1H
1H), 8.10 (t, J¼7.6 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
d 68.4, 112.4,
NMR (CDCl3, 400 MHz)
d 4.85 (s, 2H), 7.24–7.34 (m, 3H), 7.43
122.1, 124.5, 124.9, 126.1, 128.1, 128.5, 128.6, 128.7, 128.9, 129.3,
132.0, 135.1, 151.2, 165.0; IR (KBr) 1761, 1733 cmꢁ1. HRMS (EI) calcd
for C19H13NO3: 303.0895; found: m/z 303.0897.
(d, J¼7.6 Hz, 2H), 7.68–7.71 (m, 2H), 7.81–7.85 (m 2H); 13C NMR
(CDCl3, 100 MHz) d 41.6, 123.3, 127.8,128.6, 128.6, 132.1, 133.9, 136.3,
168.0; IR (KBr) 1702 cmꢁ1. Anal. Calcd for C15H11NO2: C, 75.94; H,
4.67; N, 5.90. Found: C, 76.13; H, 4.77; N, 5.94.
X-ray crystal data; Empirical formula: C19H13NO3; Formula weight
ꢀ
303.32; Crystal system¼triclinic; Space group Pı (#2); Lattice pa-
rameters: a¼9.655(2) Å; b¼11.379(1) Å, c¼7.141(1) Å;
a
¼97.14(2)ꢀ,
b
¼107.11(2)ꢀ,
g
¼100.68(1)ꢀ; V¼724.8(2) Å3; T¼23.0 ꢀC; Z¼2;
m
4.8. N,N-Dibenzylphthalimide 7
(MoK
a
)¼0.95 cmꢁ1
; 4446 reflections measured, 1763 unique
Mp 175.5–177 ꢀC (colorless solid from CH2Cl2–hexane); 1H NMR
(Rint¼0.045); final R value 0.059. Crystallographic data has been de-
posited with the Cambridge Crystallographic Data Center, CCDC No.
751601.
(CDCl3, 400 MHz)
d
4.52 (d, J¼6.0 Hz, 4H), 6.92 (s, 2H), 7.27–7.36
(m, 8H), 7.45–7.48 (m, 2H), 7.59–7.63 (m, 2H); 13C NMR (CDCl3,
100 MHz) d 44.1, 127.6, 127.9, 128.4, 128.8, 130.4, 134.5, 137.7, 168.9;
IR (KBr) 1630 cmꢁ1. HRMS (EI) calcd for C22H20N2O2: 344.1525;
4.10.1. 1-(Benzylthiocarbonyl)benzo[c,d]indol-2-one 10b. Mp
156.0–156.5 ꢀC (colorless solid from CH2Cl2–hexane); 1H NMR
found: m/z 344.1524.
(CDCl3, 400 MHz)
d 4.33 (s, 2H), 7.24–7.28 (m, 1H), 7.31–7.36
(m, 2H), 7.44–7.47 (m, 2H), 7.57 (dd, J¼7.2, 8.4 Hz, 1H), 7.70
4.9. General procedure for the preparation of 9a,b
(9a as an example)
(d, J¼8.4 Hz, 1H), 7.75 (dd, J¼7.2, 8.0 Hz, 1H), 8.10–8.13 (m, 3H); 13C
NMR (CDCl3, 100 MHz) d 34.0, 113.4, 122.7, 123.9, 125.3, 126.2, 127.3,
128.6, 128.7, 129.1, 129.2, 129.3, 132.5, 135.3, 136.9, 166.7, 167.9; IR
(KBr) 1728, 1670 cmꢁ1. Anal. Calcd for C19H13NO2S: C, 71.45; H, 4.10;
N, 4.39. Found: C, 71.45; H, 4.36; N, 4.37.
Hydroxylamine hydrochloride (525.9 mg, 7.56 mmol), and
NaHCO3 (635.1 mg, 7.56 mmol) were added to a stirred solution
of 1,8-naphthalic anhydride (1000.0 mg, 5.05 mmol) in EtOH at
refluxed and stirred for 30 min. The solvent was removed, and
some H2O and HCl (1 N) were added to the yellow resulting
residue. The colorless solid was filtered by suction filtration and
washed with ether. The solvent was removed to give N-hydroxy-
1,8-naphthalimide (895.5 g, 90%) as a colorless solid. Then, tosyl
X-ray crystal data; Empirical formula: C19H13NO2S; Formula
ꢀ
weight 319.38; Crystal system¼triclinic; Space group Pı (#2); Lattice
parameters: a¼7.210(2) Å; b¼11.405(3) Å, c¼19.057(4) Å;
a
¼75.84(2)ꢀ,
b
¼81.93(2)ꢀ,
g
¼84.97(2)ꢀ; V¼1502.1(7) Å3; T¼23.0 ꢀC;
Z¼4;
m
(MoK
a
)¼2.24 cmꢁ1; 9151 reflections measured, 2839 unique
(Rint¼0.040); final R value 0.066. Crystallographic data has been de-
posited with the Cambridge Crystallographic Data Center, CCDC No.
751599.
chloride (196.7 mg, 1.03 mmol) and pyridine (82.9 mL,
1.03 mmol) were added to the solution of N-hydroxy-1,8-naph-
thalimide (200.0 mg, 0.94 mmol) in CH2Cl2 (10 mL) and stirred
at room temperature under N2 for 30 min. The solvent was
removed, and resulting residue was separated by flash chro-
matography on silica gel using CH2Cl2 to give N-tosyloxy-1,8-
naphthalimide 9a (286.0 mg, 83%) as a colorless solid; mp
206–207 ꢀC (from CH2Cl2–hexane); 1H NMR (CDCl3, 400 MHz)
4.11. Benzo[c,d]indol-2-one 11
Mp 179.5–180 ꢀC (yellow solid from CH2Cl2–hexane); 1H NMR
(CDCl3, 400 MHz)
d
7.01 (d, J¼6.8 Hz 1H), 7.46 (dd, J¼7.2, 8.4 Hz,
1H), 7.56 (d, J¼8.0 Hz, 1H), 7.74 (dd, J¼7.2, 8.0 Hz, 1H), 8.06
d
2.51 (s, 3H), 7.43 (d, J¼8.0 Hz, 1H), 7.77–7.85 (m, 3H), 8.04
(d, J¼8.4 Hz, 1H), 8.29 (dd, J¼8.8, 8.0 Hz, 3H), 8.61–8.64 (m, 2H);
13C NMR (CDCl3, 100 MHz)
21.9, 122.2, 127.2, 127.4, 129.4, 129.8,
131.8, 132.1, 132.3, 133.4, 135.2, 135.3, 146.4, 159.8; IR (KBr) 1772,
1739, 1728, 1705 cmꢁ1
HRMS (EI) calcd for C19H13NO5S:
(d, J¼8.0 Hz,1H), 8.10 (d, J¼7.2 Hz,1H), 8.69 (s,1H); 13C NMR (CDCl3,
100 MHz) d 106.5,120.3,124.4,128.6,128.7,129.4,131.2,137.0,170.1;
d
IR (KBr) 1715 cmꢁ1. HRMS (EI) calcd for C11H7NO: 169.0528; found:
m/z 169.0523.
.
367.0514; found: m/z 367.0511.
4.12. General procedure for the preparation of 19a,b
(19a as an example)
4.9.1. N-Mesitylenesulfonyloxy-1,8-naphthalimide 9b. Mp 257–
259 ꢀC (colorless solid from CH2Cl2–hexane); 1H NMR (CDCl3,
Pyridine (1 mL) was added to a stirred solution of N-hydrox-
ysuccinimide (400.0 mg, 3.47 mmol) and tosyl chloride (728.8 mg,
3.82 mmol) in CH2Cl2 (5 mL) at room temperature under N2 and
stirred for 1 h. Then, the reaction mixture was neutralized by dil
AcOH solution and extracted with CH2Cl2. The organic layer was
separated, successively washed with water and brine, and dried
over anhydrous MgSO4. Removal of solvent in vacuum gave a solid
400 MHz)
J¼0.4, 3.8 Hz, 1H), 8.33 (dd, J¼0.8, 3.6 Hz, 2H), 8.59–8.65 (m, 2H);
13C NMR (CDCl3, 100 MHz)
21.3, 22.9, 122.3, 127.2, 127.5, 131.8,
d 2.37 (s, 3H), 2.71 (s, 6H), 7.75–7.85 (m, 3H), 8.27 (dd,
d
131.9, 132.3, 133.4, 135.1, 135.3, 140.4, 144.3, 160.0; IR (KBr) 1773,
1733, 1705 cmꢁ1. HRMS (EI) calcd for C21H17NO5S: 395.0827; found:
m/z 395.0824.

Md. Chanmiya Sheikh et al. / Tetrahedron 66 (2010) 2132–2140
2139
product, which was purified by preparative TLC (AcOEt) to give
N-tosyloxysuccinimide 19a (927.2 mg, 99%) as a colorless solid; mp
135–136 ꢀC (from CH2Cl2–hexane); 1H NMR (CDCl3, 400 MHz)
0.18 mmol) in CH2Cl2 (1.5 mL) at room temperature under N2 and
stirred for 2 h. Then, the reaction mixture was neutralized by dil
AcOH solution and extracted with CH2Cl2. The organic layer was
separated, successively washed with water and brine, and dried over
anhydrous MgSO4. Removal of solvent in vacuum gave a crude
product, which was purified by preparative TLC (hexane–AcOEt–
CH2Cl2; 1:1:1) to give benzyl 3-(benzyloxycarbonylamino)butanoate
23a (57.5 mg, 100%) as a colorless oil; 1H NMR (CDCl3, 400 MHz)
d
2.49 (s, 3H), 2.82 (s, 4H), 7.40 (d, J¼8.0 Hz, 2H), 7.94 (dd, J¼2.0,
6.6 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
d 21.9, 25.4, 129.4, 130.0,
130.9, 147.1, 168.5; IR (KBr) 1752, 1729 cmꢁ1. HRMS (EI) calcd for
C11H11NO5S: 269.0358; found: m/z 269.0352.
4.12.1. N-Mesitylenesulfonyloxysuccinimide 19b. Yield 96%; mp
d
1.81–1.88 (m, 2H), 2.40 (t, J¼7.2 Hz, 2H), 3.22 (q, J¼6.4 Hz, 2H), 4.92
(s, 1H), 5.08 (s, 1H), 5.08 (s, 2H), 5.10 (s, 2H), 7.24–7.38 (m 10H); 13C
NMR (CDCl3,100 MHz) 25.1, 31.4, 40.3, 66.3, 66.6,128.1,128.2,128.2,
128.5, 128.5, 135.8, 136.5, 156.4, 172.9; IR (KBr) 1730, 1706 cmꢁ1
145.5–147 ꢀC (colorless solid from CH2Cl2–hexane); 1H NMR (CDCl3,
400 MHz)
d
2.34 (s, 3H), 2.67 (s, 6H), 2.78 (s, 4H), 7.01 (d, J¼0.4 Hz,
d
2H); 13C NMR (CDCl3, 100 MHz)
d
21.2, 22.9, 25.3, 129.9, 131.9, 141.1,
.
145.2, 168.6; IR (KBr) 1758, 1739 cmꢁ1. HRMS (EI) calcd for
HRMS (EI) calcd for C18H19NO4: 327.1471; found: m/z 327.1452.
C13H15NO5S: 297.0671; found: m/z 297.0669.
4.15.1. N-{2 (Benzylaminocarbonyl)propyl}-N0-benzyl urea 23b. Mp
4.13. General procedure for the preparation of 20a,b
(20a as an example)
188–189 ꢀC (colorless solid from CH2Cl2–hexane); 1H NMR (CDCl3,
400 MHz)
d
1.71–1.78 (m, 2H), 2.22 (t, J¼7.2 Hz, 2H), 3.14 (t,
J¼6.4 Hz, 2H), 4.27 (s, 2H), 4.33 (d, J¼5.6 Hz, 2H), 5.87 (s, 1H), 6.21
Benzyl alcohol (57.7
mL, 0.56 mmol) and DBU (83.3
mL,
(s, 1H), 7.20–7.29 (m, 10H), 8.21 (s, 1H); 13C NMR (CDCl3, 100 MHz)
0.56 mmol) solution was added to a stirred solution of 19a
(100.0 mg, 0.37 mmol) in CH2Cl2 (2 mL) at room temperature under
N2 and stirred for 2 h. Then, the reaction mixture was neutralized
by dil AcOH solution and extracted with CH2Cl2. The organic layer
was separated, successively washed with water and brine, and
dried over anhydrous MgSO4. Removal of solvent in vacuum gave
a crude product, which was purified by preparative TLC (AcOEt) to
give benzyl 3-(benzyloxycarbonylamino)propionate 20a (70.2 mg,
d 25.2, 31.7, 37.7, 41.1, 41.9, 125.1, 125.3, 125.7, 125.8, 126.7, 126.7,
137.9, 139.1, 157.4, 170.2; IR (KBr) 1672, 1631 cmꢁ1. HRMS (EI) calcd
for C19H23N3O2: 325.1790; found: m/z 325.1785.
4.15.2. N-(Phenyloxycarbonyl)pyrrolidine-2-one 24c. Mp 114.5–
115.5 ꢀC (colorless solid from CH2Cl2–hexane); 1H NMR (CDCl3,
400 MHz)
d
2.02–2.10 (m, 2H), 2.56 (t, J¼8.2 Hz, 2H), 3.89 (t,
J¼7.0 Hz, 2H), 7.09–7.20 (m, 3H), 7.29–7.34 (m, 2H); 13C NMR
61%) as a colorless liquid; 1H NMR (CDCl3, 400 MHz)
J¼6.0 Hz, 2H), 3.46 (q, J¼6.0 Hz, 2H), 5.08 (s, 2H), 5.11 (s, 2H), 5.33
(s, 1H), 7.23–7.36 (m, 10H); 13C NMR (CDCl3, 100 MHz)
34.4, 36.5,
d
2.58 (t,
(CDCl3, 100 MHz) d 17.6, 32.8, 46.7, 121.5, 126.1, 129.4, 150.2,
173.8; IR (KBr) 1795, 1781 cmꢁ1. HRMS (EI) calcd for C11H11NO3:
d
205.0739; found: m/z 205.0725.
66.4, 66.6, 128.0, 128.0, 128.1, 128.3, 128.4, 128.5, 135.5, 136.4, 156.2,
172.1; IR (KBr) 1728, 1719 cmꢁ1. HRMS (EI) calcd for C18H19NO4:
313.1314; found: m/z 313.1311.
4.15.3. N-(Methylphenyloxycarbonyl)pyrrolidine-2-one 24d. Mp
98.0–99.0 ꢀC (colorless solid from CH2Cl2–hexane); 1H NMR (CDCl3,
400 MHz)
d
2.00–2.08 (m, 2H), 2.27 (s, 3H), 2.54 (t, J¼8.0 Hz, 2H),
4.13.1. N-{2 (Benzylaminocarbonyl)ethyl}-N0-benzyl urea 20b. Mp
3.87 (t, J¼7.2 Hz, 2H), 6.96–6.99 (m, 2H), 7.10 (d, J¼8.4 Hz, 1H); 13C
183.5–185 ꢀC (colorless solid from CH2Cl2–hexane); 1H NMR
NMR (CDCl3, 100 MHz) d 17.6, 20.8, 32.8, 46.7, 121.1, 129.9, 135.8,
(DMSO, 400 MHz)
(d, J¼5.6 Hz, 2H), 4.18 (d, J¼5.6 Hz, 2H), 5.92 (s, 1H), 6.39 (s, 2H),
7.02–7.38 (m, 10H), 8.32 (s, 1H); 13C NMR (DMSO, 100 MHz)
31.6,
d
2.23 (t, J¼7.6 Hz, 2H), 3.18 (t, J¼6.2 Hz, 2H), 4.10
148.0, 173.9; IR (KBr) 1786, 1697 cmꢁ1. HRMS (EI) calcd for
C12H13NO3: 219.0895; found: m/z 219.0901.
d
31.8, 37.7, 38.5, 122.2, 122.4, 122.7, 122.9, 123.9, 135.2, 136.6, 153.7,
166.5; IR (KBr) 1684, 1635 cmꢁ1. HRMS (EI) calcd for C18H21N3O2:
311.1634; found: m/z 311.1632.
Supplementary data
Supplementary data that may be helpful in the review process
should be prepared and provided as a separate electronic file. That
file can then be transformed into PDF format and submitted along
with the manuscript and graphic files to the appropriate editorial
office. Supplementary data associated with this article can be found
in the online version at, doi:10.1016/j.tet.2010.01.074.
4.14. Preparation of N-tosyloxyglutarimide 22
Hydroxylamine hydrochloride (913.0 mg, 13.5 mmol), and
NaHCO3 (1104.7 mg,13.15 mmol) were added to a solution of glutaric
anhydride (1000.0 mg, 8.76 mmol) in ethanol at refluxed and stirred
for 12 h. The solvent was removed, in vacuum, and dried at 80 ꢀC to
give crude solid. Then, tosyl chloride (1837.9 mg, 9.64 mmol) and
References and notes
pyridine (1219.0 mL, 13.15 mmol) were added to the crude solid in
1. For reviews and recent examples, see: (a) Dubowchick, G. M.; Walker, M. A.
Pharmacol. Ther. 1999, 83, 67; (b) Rusiecki, V. K.; Warne, S. A. Bioorg. Med. Chem.
Lett. 1993, 3, 707; (c) Janda, K. D.; Ashley, J. A.; Jones, T. M.; McLeod, D. A.;
Schloeder, D. M.; Weinhouse, M. I. J. Am. Chem. Soc. 1990, 112, 8886; (d) Pietersz,
G. A. Bioconjugate Chem. 1990, 1, 89.
2. Dalton, K. H.; Dubowchik, G. M.; Michael, A. W. Tetrahedron Lett. 2002, 43, 1987.
3. (a) Morita, H.; Byung, J. K. Chem. Lett. 2000, 42; (b) Morita, H.; Byung, J. K.;
Yamada, S.; Funada, T.; Kadoma, Y. Bioorg. Med. Chem. Lett. 2000, 10, 357.
4. Morita, H; Sheikh, M.C.; Byung, J.K.; Takagi, S.; Sakai, M.; unpublished work.
5. Sheikh, M. C.; Takagi, S.; Sakai, M.; Abe, H.; Morita, H. Org. Biomol. Chem. 2008,
6, 4505.
6. Katrizky, A. R.; Lan, X.; Yang, J. Z.; Denisko, O. V. Chem. Rev. 1998, 98, 409.
7. Takagi, S.; Sheikh, M. C.; Ogasawara, A.; Ohira, M.; Abe, H.; Morita, H. Hetero-
cycles 2009, 78, 1433.
8. (a) Fahmy, A. F. M.; Ali, N. F.; Nada, A.; Ali, N. Y. Bull. Chem. Jpn. 1977, 50, 2678;
(b) Lossen, W. Liebigs Ann. Chem. 1872, 175, 271; (c) Ulrich, H.; Tucer, B.; Richter,
R. J. Org. Chem. 1978, 43, 1544; (d) Maillard, T. L.; Benohoud, M.; Durand, P.;
Badet, B. J. Org. Chem. 2005, 70, 6303; (e) Stolberg, M. A.; Tweit, R. C.; Steinberg,
G. M.; Wagner-Jauregg, T. J. Am. Chem. Soc. 1955, 77, 765; (f) Hurd, C. D.; Bauer, L.
J. Am. Chem. Soc. 1954, 76, 2791; (g) Castro, E. A.; Pavez, P.; Santos, J. G. J. Org.
CH2Cl2 and stirred at room temperature under N2 for 30 min. The
solvent was removed, and resulting residue was separated by flash
chromatography on silicagel using CH2Cl2 to give 22(1315.0 mg, 53%)
as a colorless solid; mp 145.5–146 ꢀC (from CH2Cl2–hexane); 1H NMR
(CDCl3, 400 MHz)
d
1.99–2.05 (m, 2H), 2.47 (s, 3H), 2.81 (t, J¼6.6 Hz,
4H), 7.37 (dd, J¼0.8, 8.4 Hz, 2H), 7.89–7.92 (m, 2H); 13C NMR (CDCl3,
100 MHz)
d 16.5, 21.8, 33.3, 129.3, 129.8, 131.8, 146.4, 166.7; IR (KBr)
1757, 1728 cmꢁ1. Anal. Calcd for C12H13NO5S: C, 50.87; H, 4.63; N, 4.94.
Found: C, 50.84; H, 4.62; N, 4.87.
4.15. General procedure for the preparation of 23a–d and
24a–d (23a as an example)
Benzyl alcohol (38.3
mL, 0.37 mmol) and DBU (55.2 mL,
0.37 mmol) solution was added to a stirred solution of 22 (50.0 mg,

2140
Md. Chanmiya Sheikh et al. / Tetrahedron 66 (2010) 2132–2140
Chem. 2002, 67, 4494; (h) Tundo, P.; Selve, M. Acc. Chem. Res. 2002, 35, 706; (i)
Castro, E. A. Chem. Rev. 1999, 99, 3505.
19. (a) Okunrobo, L. O.; Usifoh, C. O. Pak. J. Pharm.. Sci. 2006, 19, 309; (b) Sheehan, J.
C.; Holland, G. I. J. Am. Chem. Soc. 1956, 78, 5631.
9. (a) Hoare, D. G.; Olson, A.; Koshland, D. E. J. Am. Chem. Soc. 1968, 90, 1638; (b)
Linke, S.; Tisue, G. T.; Lwowski, W. J. Am. Chem. Soc. 1967, 89, 6308; (c) Joensson,
N. A.; Moses, P. Acta Chem. Scand. 1974, 28, 441; (d) Groutas, W. C.; Stanga, M.
A.; Brubaker, M. J. J. Am. Chem. Soc. 1989, 111, 1931; (e) Adams, G. W.; Bowie, J.
H.; Hayes, R. N. J. Chem. Soc., Perkin Trans. 2 1991, 689.
10. (a) Jin, W.; Trzupec, J. D.; Rayl, T. J.; Broward, M. A.; Weir, S. J.; Hwang, I.; Boger,
D. L. J. Am. Chem. Soc. 2007, 129, 15391; (b) Stefanowiez, P.; Jaremko, L.; Jaremko,
M.; Lis, T. New J. Chem. Soc. 2006, 30, 258.
11. (a) Aoai, T.; Kodama, K.; Yamanaka, T.; Yagihara, M. J. Photopolym. Sci. Technol.
1998, 11, 409; (b) Abramovitch, R.; Beckert, J. M.; Chinnasamy, P. X. H.; Pen-
nington, W.; Sanjivamurthy, A. R. V. Heterocycles 1989, 28, 623.
12. (a) Roos, G. H. P.; Dastlik, K. A. Heterocycles 2003, 60, 2023; (b) Barker, D.;
McLeod, M. D.; Brimble, M. A.; Savage, G. P. Tetrahedron Lett. 2001, 42,
1785.
20. (a) Molval, J. P.; Suzuki, S.; Mortel-Saary, F.; Takahara, S.; Yamaoka, T. J. Phys. Chem.
A 2008, 112, 3879; (b) Neumann, U.; Guetschow, M. J. Biol. Chem.1994, 269, 21561.
21. Stradin, J.; Baumane, L.; Gavars, R.; Magda, V.; Samusenko, Y. Khimiya Geter-
otsiklieheskikh Soedinnenii 1993, 8, 1068.
22. (a) Takas, A.; Acs, P.; Kollar, L. Tetrahedron 2007, 64, 983; (b) Barooah, N.;
Tamuly, C.; Baruah, J. B. J. Chem. Sci. (Banglalore, India) 2005, 117, 117.
23. (a) Tokita, S.; Watanabe, F.; Hashimoto, K.; Tachikawa, T. J. Photopolym. Sci.
Technol. 2001, 14, 221; (b) Adegawa, Y. Jpn. kokai Tokkyo koho 2002, 44.
24. Khumtaveeporn, K.; Ullmann, A.; Matsumoto, K.; Davis, B. G.; Jones, J. B. Tet-
rahedron: Asymmetry 2001, 12, 249.
25. (a) Imi, Y.; Ueda, M.; Ishimori, M. J. Polymer Sci. Polymer Chemistry Edition 1976,
14, 299; (b) Gross, H.; Bilk, L. Tetrahedron 1968, 24, 6935.
26. Barbayianni, E.; Fotakopoulou, I.; Schmidt, M.; Constantinou-kokotou, V.;
Bornscheuer, U. J. Org. Chem. 2005, 70, 8730.
13. (a) Chapman, T. M.; Freedman, E. A. J. Org. Chem. 1973, 38, 3908; (b) Gro-
chowski, E.; Jurezak, J. J. Org. Chem. 1978, 43, 2541.
14. (a) Barker, D.; Brimble, M. A.; McLeod, M. D. Tetrahedron 2004, 60, 5953; (b)
Kiely, J. S.; Huang, S. J. Heterocycl. Chem. 1987, 24, 1137.
15. (a) Venuti, M. C. Synthesis 1982, 4, 266; (b) Ongania, K. H.; Egerbacher, H.
Monatshefte fur chemie 1985, 116, 979.
16. (a) Nammert, V.; Travnikova, O.; Vahur, S.; Leito, I.; Piiralu, M.; Maemets, V.;
Koppel, I.; Ilmar, A. J. Phys. Org. Chem. 2006, 19, 654; (b) Fife, T. H.; Singh, R.;
Bembi, R. J. Org. Chem. 2002, 67, 3179.
27. (a) Yano, T.; Shinohara, S.; Takeyama, C. PCT Int. Appl. 2003, 33; (b) Onomura, O.;
Moriyama, A.; Fukae, K.; Yamamoto, Y.; Maki, T.; Matsumura, Y.; Demizu, Y.
Tetrahedron Lett. 2008, 49, 6728.
28. Hamaguchi, F.; Nagasaka, T.; Sakurai, E. Eur. Pat. Appl. 1991, 16.
29. (a) Kobayashi, S.; Matsubara, R.; Kitagawa, H. Org. Lett. 2002, 4, 143; (b) Ueno,
M.; Ishitani, H.; Kobayashi, S. Org. Lett. 2002, 4, 3395; (c) Badorrey, R.; Cativiela,
C.; Daiz-de-Villegas, M. D.; Galvez, J. A. Tetrahedron Lett. 2003, 44, 9189; (d)
Periasamy, M.; Suresh, S.; Ganesan, S. S. Tetrahedron Lett. 2005, 46, 5521; (e)
Jacobsen, M. F.; Ionita, L.; Skrydstrup, T. J. Org. Chem. 2004, 69, 4792; (f) Komoto,
I.; Kobayashi, S. J. Org. Chem. 2004, 69, 680; (g) Chung, W. J.; Omote, M.; Welch,
J. T. J. Org. Chem. 2005, 70, 7784; (h) Pandey, G.; Singh, R. P.; Garg, A.; Singh, V.
K. Tetrahedron Lett. 2005, 46, 2137.
17. (a) Imai, Y.; Ueda, M.; Ishimori, M. J. Polym. Sci. 1975, 13, 1969; (b) EI-Soghier, A.
H. Egypt. J. Chem. 1997, 40, 339.
18. Worlikar, S. A.; Larock, R. C. J. Org. Chem. 2008, 73, 7175.