One-pot synthesis of photochromic 6′-amino-substituted spirooxazines from 1-nitroso-2-naphthol zinc chelate and indoline base

Article abstract of DOI:10.1055/s-0030-1258197

A series of spirooxazine derivatives containing nitrogen heterocycles were synthesized through the condensation of 2-methylene-1,3,3-trimethylindoline derivatives with the zinc salt of 1-nitroso-2-naphthol using ethanol as solvent. The method is simple, starts from readily accessible and inexpensive reagents, and leads to the synthesis of 6′-substituted spirooxazines in moderate to good yields. We simplified the workup and found that, for some target compounds, recrystallization can effectively improve efficiency of the separation and purification. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258197

3
418
PAPER
One-Pot Synthesis of Photochromic 6¢-Amino-Substituted Spirooxazines from
-Nitroso-2-naphthol Zinc Chelate and Indoline Base
1
S
M
ynthesis of
6
¢
-Amino
e
i
Spir
o
-
Department of Chemistry, Nankai University, Tianjin 300071, P. R. of China
Fax +82(22)23502230; E-mail: pangmeili@nankai.edu.cn; E-mail: mengjiben@nankai.edu.cn
Received 10 May 2010; revised 1 July 2010
2
'
1'
10'
6'
9'
Abstract: A series of spirooxazine derivatives containing nitrogen
heterocycles were synthesized through the condensation of 2-meth-
ylene-1,3,3-trimethylindoline derivatives with the zinc salt of 1-ni-
troso-2-naphthol using ethanol as solvent. The method is simple,
starts from readily accessible and inexpensive reagents, and leads to
the synthesis of 6¢-substituted spirooxazines in moderate to good
yields. We simplified the workup and found that, for some target
compounds, recrystallization can effectively improve efficiency of
the separation and purification.
N
8'
3
N
'
O
7'
4
'
Me
5
'
indoline
fragment
oxazine
fragment
Figure 1
Key words: spirooxazines, heterocycles, condensation, photo-
chromism, one-pot synthesis
NO
a
OH
In recent years, photochromic organic compounds have
been extensively studied because of their application in
2
NH ⋅HCl
O
NH
N
OH
b
1
,2
science and technology. In addition to their potential ap-
plications utilizing their different absorption properties,
the changes in electron delocalization have also been em-
ployed for the design of photoswitchable nonlinear optical
N
O
Me
NO
1
N
O–
N
Zn2
+ c
3
4–7
Me
devices, luminescent devices, host–guest systems and
enzymatic systems.
O
8
–11
Spirooxazine (SPOs) are one of
2
the most popular classes of photochromic materials, and
Scheme 1 Reagents and conditions: (a) method A: ClHC=CCl ; (b)
have been shown to possess high fatigue resistance and
2
1
2
method B: DMSO, Et N, MeOH; (c) method C: EtOH.
3
excellent photostability. According to our previous re-
1
3
port, photochromic spirooxazines containing nitrogen
heterocycles at the 6¢-position exhibited remarkable fa-
tigue resistance and substantial bathochromic shifts in the
absorption spectra of the open forms in both solution and
in polymers. Because these properties greatly increase
their potential applications, the direct synthesis of these
compounds thus assumes great importance.
ous secondary amines as nucleophiles for the preparation
of 4-amino-substituted 1,2-naphthoquinones, which were
then employed in the synthesis of 6¢-amino-substituted
SPOs. These authors also developed a simplified (but
much less universal) approach to the synthesis of the same
compounds based on the reaction of 1-nitroso-2-naphthol,
a secondary amine, and Fischer’s base, without isolation
of the substituted nitrosonaphthol, which partially ac-
In recent years, abundant new data on the synthesis of
SPOs have become available. The synthesis of this type of
compound from aromatic o-hydroxynitroso compounds
or from 1-amino-2-naphthols and related compounds are
16
counts for the low yield. In 2005, Koshkin et al. reported
a one-pot synthesis of 6¢-amino-substituted spirooxazines.
1
4
commonly used methods. The two fragments that make
up the SPO molecule will be referred to as the indoline
and oxazine fragments (Figure 1).
We used three different methods for the preparation of
1
,3,3-trimethyl-6¢-morpholinospiro(indoline-2,3¢-naph-
tho[2,1-b][1,4]oxazine) (1; Scheme 1). Our experiments
showed that using method A,13 the synthesis needed a
short reaction time, but resulted in a low yield; method B16
uses expensive 1-aminonaphthol hydrochloride, which
can easily be oxidized. We thus designed method C for the
synthesis of 6¢-substituted SPOs by considering that zinc
ions could be effectively chelated with oxygen atoms to
form a coordination compound, thus promoting the link-
age of the naphthalene fragment with N-heterocycles.
During the course of the reaction, the zinc complexes of
1-nitroso-2-naphthol are able to react with secondary
Most of the procedures that have been used for structural
modification of the oxazine fragment in SPOs are based
on the insertion of a substituent into the naphthalene frag-
ment. However, because it is relatively difficult to access
4
-substituted 2-naphthols, the 6¢-substituted SPOs are less
14 15
common. Thus, Rickwood and co-workers used vari-
SYNTHESIS 2010, No. 20, pp 3418–3422
x
x.
x
x
.
2
0
1
0
Advanced online publication: 04.08.2010
DOI: 10.1055/s-0030-1258197; Art ID: F08010SS
Georg Thieme Verlag Stuttgart · New York
©

PAPER
Synthesis of 6¢-Amino-Substituted Spirooxazines
Table 2 Effect of Additives on Reaction Yielda–c
3419
NO
NOH
OH
O
Zn2+
2
-Methylene-1,3,3-trimethylindoline
Additive (0.2 g)
Yield
(
mol)
(%)
51
63
69
58
48
1
2
NHR R
0.001
.001
–
0
MgSO4
O
0.001
0.001
NaSO4
NOH
O
N
N
Zn2+
OH
O–
O
MS
O
0
.001
activated carbon
1
2
H
NR R
a
b
c
1
-Nitroso-2-naphthol zinc salt (0.006 mol).
1
2
NHR R
Heated at reflux in EtOH (40 mL) for 20 h
Nitrogen atmosphere.
NOH
N
O
N
Me
Table 3 Effect of Reaction Time on Yielda–d
N
O
1
2
Me
NR R
NR1R2
2-Methylene-1,3,3-trimethylindoline
mol)
Time (h)
Yield (%)
(
Scheme 2 Reaction mechanism
0
0
0
0
0
.001
.001
.001
.001
.001
4
12
42
65
71
62
amines through
a
Michael addition mechanism
10
16
20
24
1
4,15
(
Scheme 2).
In this process, the zinc chelate of an
ortho-hydroxynitrosoaromatic compound favors the syn-
thesis of 4-substituted-2-naphthols. On the basis of mech-
anistic studies, we also optimized the synthetic conditions
of a general preparative method. The optimized data are
listed in Tables 1 through 3.
a
b
c
d
1
-Nitroso-2-naphthol zinc salt (0.006 mol).
Heated at reflux in EtOH (40 mL).
NaSO (0.2 g) added.
Nitrogen atmosphere.
Table 1 Effect of Solvent on Reaction Yielda–d
4
2
-Methylene-1,3,3-trimethylindoline
Solvent (40 mL)
Yield
(%)
(
mol)
0
0
0
.001
.001
.001
trichloroethylene 12
hours were optimal. Under these conditions, spiroox-
azine-containing nitrogen heterocycles 1–11 were ob-
tained in moderate to good yields (Scheme 3, Table 4).
EtOH
70
53
MeOH
a
b
c
d
1
-Nitroso-2-naphthol zinc salt (0.006 mol).
NO
NO
O–
Heated at reflux for 20 h.
NaSO (0.2 g) added.
Nitrogen atmosphere.
OH
ZnCl2
2
R H
Zn2+
4
EtOH, reflux
2
Regarding the data presented in Table 1, it can be con-
cluded that the yield can be improved in polar solvents,
presumably because the reactants (zinc chelates) have rel-
atively strong polarities. In addition, the yield obtained in
ethanol as solvent was higher than that obtained in meth-
anol; this can be attributed to the fact that ethanol is a
more suitable solvent for the hydrophobic part of the reac-
tant. From Table 2, it can be seen that adding desiccant to
the reaction significantly increased the yield; anhydrous
sodium sulfate was the best, which could be due to the fact
that it is a neutral desiccant that can absorb large amounts
of water. When activated carbon was added to the reaction
the yield decreased, which may be because some product
was adsorbed. The data presented in Table 3 show that,
under a nitrogen atmosphere, reaction times of 16–20
R1
NO
N
O–
R1
N
Me
Zn2+
NaSO4, N2
N
O
2
R2
Me
R2
1–11
1
2
Scheme 3 Optimized synthetic route (R = H, Cl; R = N-hetero-
cycle)
In summary, the condensation of substituted indoline
bases with the zinc salt of 1-nitroso-2-naphthols in the
presence of cyclic secondary amines can be successfully
Synthesis 2010, No. 20, 3418–3422 © Thieme Stuttgart · New York

3
420
M.-L. Pang et al.
PAPER
Table 4 Prepared 6¢-Amino-Substituted Spirooxazines 1–11
was stirred for an additional 20 h. After removal of the solvent, the
residue was purified by column chromatography on silica gel (pe-
troleum ether–EtOAc).
Product
R1 R2
Yield (%)
1
2
3
4
5
6
7
8
9
H
morpholinyl
74
68
68
67
52
65
49
56
45
46
65
1
,3,3-Trimethyl-6¢-morpholinospiro(indoline-2,3¢-naphtho[2,1-
b][1,4]oxazine) (1)
Mp 192–193 °C (Lit. 196 °C).
Cl
H
morpholinyl
1
5
piperidyl
IR (KBr): 3066, 2935, 2844, 1610, 1586, 1486, 1448, 1408, 1361,
1
–
1
302, 1240, 1201, 1138, 1028, 886, 849, 815, 763, 739 cm .
Cl
H
piperidyl
1
H NMR (300 MHz, CDCl ): d = 1.36 [s, 6 H, C(CH ) ], 2.17 (s,
3
3 2
thiomorpholinyl
indolinyl
3 H, NCH ), 3.07 [m, 4 H, N(CH ) ], 3.94 [m, 4 H, O(CH ) ], 6.57
3 2 2 2 2
(
7
2
d, J = 7.8 Hz, 1 H, H-7), 6.62 (s, 1 H, H-5¢), 6.89 (dd, J = 7.0,
H
.4 Hz, 1 H, H-5), 7.10 (d, J = 7.2 Hz, 1 H, H-4), 7.22 (dd, J = 8.2,
.2 Hz, 1 H, H-6), 7.38 (ddd, J = 8.2, 8.2, 1.3 Hz, 1 H, H-8¢), 7.56
Cl
H
indolinyl
(
ddd, J = 8.2, 8.2, 1.3 Hz, 1 H, H-9¢), 7.65 (s, 1 H, H-2¢), 8.05 (d,
J = 8.6 Hz, 1 H, H-7¢), 8.56 (d, J = 7.9 Hz, 1 H, H-10¢).
1,2,3,4-tetrahydroisoquinolinyl
1,2,3,4-tetrahydroisoquinolinyl
1,2,3,4-tetrahydroquinolinyl
piperazinyl
1
3
C NMR (75 MHz, CDCl ): d = 20.6 (CH ), 25.3 (CH ), 29.5
3
3
3
Cl
H
(
1
NCH ), 51.5 (C-3), 53.3 (2 × C, NCH ), 67.1 (2 × C, OCH ), 98.7–
3
2
2
51.6 (18 × C, ArC, C-2¢).
1
1
0
1
MS (ESI): m/z = 414.2 [M + H]+.
H
Anal. Calcd for C H N O : C, 75.52; H, 6.58; N, 10.16. Found: C,
2
6
27
3
2
7
5.57; H, 6.63; N, 10.11.
applied to the synthesis of spirooxazines substituted with
secondary cyclic amines at the 6¢-position. The yield of
the products depends on the nature and structure of the
secondary cyclic amines. The method is simple and starts
from readily accessible and inexpensive reagents, leading
to the synthesis of 6¢-substituted spirooxazines in moder-
ate to good yields. In addition, we have optimized the syn-
thetic conditions, simplified the workup, and found that,
for some compounds, recrystallization can effectively im-
prove the efficiency of the separation and purification of
the products. The synthesis of some compounds (e.g., 1)
5
-Chloro-1,3,3-trimethyl-6¢-morpholinospiro(indoline-2,3¢-
naphtho[2,1-b][1,4]oxazine) (2)
Mp 204–206 °C (Lit. 196 °C).
1
5
IR (KBr): 3071, 2956, 2846, 1612, 1586, 1481, 1412, 1354, 1293,
1
–
1
265, 1201, 1185, 1027, 923, 888, 806, 758, 700 cm .
1
H NMR (300 MHz, CDCl ): d = 1.34 (s, 3 H, CH ), 1.35 (s, 3 H,
3
3
CH ), 2.73 (s, 3 H, NCH ), 3.07 [m, 4 H, N(CH ) ], 3.95 [m, 4 H,
3
3
2 2
O(CH ) ], 6.47 (d, J = 8.2 Hz, 1 H, H-7), 6.60 (s, 1 H, H-5¢), 7.02
2
2
(
(
1
d, J = 2.1 Hz, 1 H, H-4), 7.16 (dd, J = 8.2, 2.2 Hz, 1 H, H-6), 7.39
ddd, J = 8.2, 8.2, 1.2 Hz, 1 H, H-8¢), 7.57 (ddd, J = 8.2, 8.2, 1.2 Hz,
H, H-9¢), 7.62 (s, 1 H, H-2¢), 8.06 (d, J = 8.3 Hz, 1 H, H-7¢), 8.55
may be applied to industrial production after additional (d, J = 8.4 Hz, 1 H, H-10¢).
optimization of the synthetic conditions.
13
C NMR (75 MHz, CDCl ): d = 20.4 (CH ), 25.2 (CH ), 29.6
3
3
3
(
1
NCH ), 51.5 (C-3), 53.3 (2 × C, NCH ), 67.1 (2 × C, OCH ), 98.7–
3
2
2
62.2 (18 × C, ArC, C-2¢).
All starting materials are commercially available. Solvents were
used without further purification and dried over molecular sieves, if
MS (ESI): m/z = 448.27 [M + H]+.
necessary. Melting points were determined with a Yanagimoto MP-
Anal. Calcd for C H ClN O : C, 69.71; H, 5.85; N, 9.38. Found:
C, 69.75; H, 5.89; N, 9.35.
1
26 26
3
2
3
5 melting point apparatus and are uncorrected. H NMR spectra
were recorded with a Bruker AC-P300 spectrometer with TMS as
internal standard, as solutions in CDCl . Mass spectra were record-
3
1
,3,3-Trimethyl-6¢-piperidinospiro(indoline-2,3¢-naphtho[2,1-
ed with a Thermo Finnigan LCQ Advantage spectrometer in ESI
mode-I. Elemental analyses were performed with a Yanaco CHN
CORDER MT-3 apparatus. IR spectra were recorded with a Bio-
Rad FTS 135 spectrophotometer using KBr disks; wavenumbers are
b][1,4]oxazine) (3)
Mp 228–230 °C (Lit. 238–239 °C).
15
IR (KBr): 3047, 2954, 2851, 1609, 1586, 1484, 1448, 1408, 1362,
1300, 1267, 1199, 1138, 1027, 891, 858, 831, 763, 731 cm .
–
1
–1
given in cm . The identification of previously reported reaction
1
products were made by comparison of their respective H NMR
1
H NMR (300 MHz, CDCl ): d = 1.35 (s, 3 H, CH ), 1.36 (s, 3 H,
3
3
spectra and melting points with literature data.
CH ), 1.63 (m, 2 H, CH ), 1.82 (m, 4 H, 2 × CH ), 2.75 (s, 3 H,
NCH ), 3.02 [m, 4 H, N(CH ) ], 6.56 (d, J = 7.8 Hz, 1 H, H-7), 6.59
3
2
2
3
2 2
Synthesis of Spirooxazines 1–11; General Procedure
(
s, 1 H, H-5¢), 6.89 (dd, J = 7.4, 8.1 Hz, 1 H, H-5), 7.10 (d,
Under stirring, ZnCl (1.36 g, 10 mmol) in H O (40 mL) was added
2
2
J = 7.1 Hz, 1 H, H-4), 7.22 (ddd, J = 7.7, 7.6, 1.3 Hz, 1 H, H-6),
7.38 (ddd, J = 8.2, 8.2, 1.3 Hz, 1 H, H-8¢), 7.55 (ddd, J = 8.2, 8.2,
to a mixture of THF–H O (1:1 v/v, 80 mL) containing 1-nitroso-2-
2
naphthol (3.98 g, 23 mmol). The mixture was stirred at r.t. for 20
min. When the reaction was complete, the crude 1-nitroso-2-naph-
1
7
.3 Hz, 1 H, H-9¢), 7.62 (s, 1 H, H-2¢), 8.02 (d, J = 8.2 Hz, 1 H, H-
¢), 8.54 (d, J = 8.3 Hz, 1 H, H-10¢).
thol zinc salt was filtered, washed with H O (3 × 20 mL) and dried
2
13
C NMR (75 MHz, CDCl ): d = 20.6 (CH ), 24.4 (CH ), 25.3
3
3
3
under an infrared heat lamp. The zinc salt (96% yield) was used for
the next step without further purification.
(
CH ), 26.3 (2 × C, CH ), 29.5 (NCH ), 51.4 (C-3), 54.4 (2 × C,
3
2
3
NCH ), 98.6–153.3 (18 × C, ArC, C-2¢).
MS (ESI): m/z = 412.47 [M + H]+.
2
1
-Nitroso-2-naphthol zinc salt (1.0 mmol) and nitrogen heterocycle
(3.5 mmol) were added to EtOH (20 mL). The resulting mixture was
heated to reflux and stirred for 2 h. Indoline base (1.5 mmol) in
EtOH (20 mL) was added to the solution under a nitrogen atmo-
sphere, anhydrous Na SO (0.3 g) was then added and the mixture
Anal. Calcd for C H N O: C, 78.80; H, 7.10; N, 10.21. Found: C,
78.58; H, 7.13; N, 10.19.
2
7
29
3
2
4
Synthesis 2010, No. 20, 3418–3422 © Thieme Stuttgart · New York

PAPER
Synthesis of 6¢-Amino-Substituted Spirooxazines
3421
5
-Chloro-1,3,3-trimethyl-6¢-piperidinospiro(indoline-2,3¢-
IR (KBr): 3045, 2961, 2842, 1618, 1588, 1482, 1413, 1352, 1292,
1242, 1164, 1026, 959, 878, 831, 818, 769, 747, 705 cm .
–
1
naphtho[2,1-b][1,4]oxazine) (4)
Mp 229–231 °C (Lit.1 220–222 °C).
5
1
H NMR (300 MHz, CDCl ): d = 1.33 (s, 3 H, CH ), 1.36 (s, 3 H,
3 3 2
3
3
IR (KBr): 3068, 2930, 2804, 1612, 1566, 1481, 1412, 1352, 1277,
1
CH ), 2.74 (s, 3 H, NCH ), 3.17 (m, 2 H, CH ), 3.93 (m, 2 H,
–1
240, 1202, 1161, 1029, 964, 884, 869, 809, 760, 699 cm .
NCH ), 6.29 (d, J = 7.9 Hz, 1 H, H-7¢¢), 6.47 (d, J = 8.2 Hz, 1 H, H-
2
1
7), 6.74 (dd, J = 7.3, 7.3 Hz, 1 H, H-5¢¢), 6.92 (s, 1 H, H-5¢), 6.93 (d,
J = 7.5 Hz, 1 H, H-4¢¢), 7.02 (d, J = 1.9 Hz, 1 H, H-4), 7.15, 7.20 (2
H NMR (300 MHz, CDCl ): d = 1.33 (s, 3 H, CH ), 1.34 (s, 3 H,
3
3
CH ), 1.64 (m, 2 H, CH ), 1.85 (m, 4 H, 2 × CH ), 2.72 (s, 3 H,
NCH ), 3.03 [m, 4 H, N(CH ) ], 6.47 (d, J = 8.2 Hz, 1 H, H-7), 6.58
3
2
2
×
d, J = 8.0, 7.6 Hz, 2 H, H-6, H-6¢¢), 7.35 (ddd, J = 8.4, 8.2, 1.3 Hz,
H, H-8¢), 7.60 (ddd, J = 7.4, 7.5, 1.3 Hz, 1 H, H-9¢), 7.66 (s, 1 H,
3
2 2
1
(
s, 1 H, H-5¢), 7.02 (d, J = 2.1 Hz, 1 H, H-4), 7.15 (dd, J = 8.2,
.1 Hz, 1 H, H-6), 7.39 (ddd, J = 8.2, 6.9, 1.2 Hz, 1 H, H-8¢), 7.55
ddd, J = 8.2, 8.2, 1.2 Hz, 1 H, H-9¢), 7.59 (s, 1 H, H-2¢), 8.06 (d,
J = 8.4 Hz, 1 H, H-7¢), 8.53 (d, J = 8.4 Hz, 1 H, H-10¢).
H-2¢), 7.96 (d, J = 8.3 Hz, 1 H, H-7¢), 8.60 (d, J = 8.2 Hz, 1 H, H-
2
(
1
0¢).
1
3
C NMR (75 MHz, CDCl ): d = 20.5 (CH ), 25.2 (CH ), 28.8
3
3
3
1
3
(CH
2
), 29.7 (NCH
3
), 51.6 (C-3), 55.1 (NCH ), 98.7–162.2 (24 × C,
2
C NMR (75 MHz, CDCl ): d = 20.5 (CH ), 24.4 (CH ), 25.2
3
3
2
ArC, C-2¢).
MS (ESI): m/z = 480.78 [M + H]+.
Anal. Calcd for C H ClN O: C, 75.07; H, 5.46; N, 8.75. Found: C,
(
CH ), 26.3 (2 × C, CH ), 29.6 (NCH ), 51.4 (C-3), 54.4 (2 × C,
3
2
3
NCH ), 98.6–153.5 (18 × C, ArC, C-2¢).
2
MS (ESI): m/z = 446.31 [M + H]+.
3
0
26
3
7
5.04; H, 5.47; N, 8.77.
Anal. Calcd for C H ClN O: C, 72.71; H, 6.33; N, 9.42; Found: C,
2
7
28
3
7
2.75; H, 6.35; N, 9.43.
1
,3,3-Trimethyl-6¢-1,2,3,4-tetrahydroisoquinolinospiro(indo-
line-2,3¢-naphtho[2,1-b][1,4]oxazine) (8)
Mp 187–188 °C.
1
,3,3-Trimethyl-6¢-thiomorpholinospiro(indoline-2,3¢-naph-
tho[2,1-b][1,4]oxazine) (5)
Mp 179–181 °C (Lit.1 184–185 °C).
5
IR (KBr): 3051, 2930, 2875, 1584, 1486, 1408, 1367, 1304, 1266,
1
–
1
240, 1192, 1102, 1031, 934, 892, 843, 743 cm .
IR (KBr): 3060, 2953, 2903, 1610, 1586, 1484, 1448, 1409, 1360,
1
–
1
1
297, 1239, 1195, 1116, 1026, 960, 870, 835, 748 cm .
H NMR (300 MHz, CDCl ): d = 1.36 (s, 3 H, CH ), 1.38 (s, 3 H,
3
3
1
CH
3
), 2.77 (s, 3 H, NCH
3
), 3.13 (m, 2 H, CH
2
), 3.39 (m, 2 H, CH ),
2
H NMR (300 MHz, CDCl ): d = 1.35 [s, 6 H, C(CH ) ], 2.75 (s,
3
3 2
4
5
4
7
.25 (s, 2 H, CH ), 6.56 (d, J = 7.7 Hz, 1 H, H-7), 6.70 (s, 1 H, H-
2
3
H, NCH ), 2.89 [m, 4 H, N(CH ) ], 3.30 [m, 4 H, S(CH ) ], 6.57
3 2 2 2 2
¢), 6.89 (m, 1 H, H-5), 7.08 (m, 2 H, H-4, H-5¢¢), 7.20 (m, 4 H, H-
¢¢, H-6, H-6¢¢, H-7¢¢), 7.36 (ddd, J = 8.2, 8.1, 1.3 Hz, 1 H, H-8¢),
.57 (ddd, J = 8.2, 8.2, 1.3 Hz, 1 H, H-9¢), 7.65 (s, 1 H, H-2¢), 8.09
(
d, J = 7.8 Hz, 1 H, H-7), 6.62 (s, 1 H, H-5¢), 6.89 (dd, J = 7.1,
7
7
7
.2 Hz, 1 H, H-5), 7.09 (d, J = 6.6 Hz, 1 H, H-4), 7.22 (ddd, J = 7.7,
.6, 1.3 Hz, 1 H, H-6), 7.38 (ddd, J = 7.1, 7.0, 1.3 Hz, 1 H, H-8¢),
.56 (ddd, J = 7.1, 7.0, 1.3 Hz, 1 H, H-9¢), 7.65 (s, 1 H, H-2¢), 7.99
(
d, J = 8.4 Hz, 1 H, H-7¢), 8.58 (d, J = 8.1 Hz, 1 H, H-10¢).
1
3
(
d, J = 8.3 Hz, 1 H, H-7¢), 8.55 (d, J = 8.2 Hz, 1 H, H-10¢).
C NMR (75 MHz, CDCl ): d = 20.6 (CH ), 25.3 (CH ), 29.5
3
3
3
1
3
(CH
2
), 29.5 (NCH
3
), 51.4 (C-3), 51.5 (CH
2
), 54.8 (CH
2
), 98.6–
C NMR (75 MHz, CDCl ): d = 20.6 (CH ), 25.4 (CH ), 28.3 (2 ×
3
3
3
1
51.8 (24 × C, ArC, C-2¢).
MS (ESI): m/z = 460.47 [M + H]+.
Anal. Calcd for C H N O: C, 81.02; H, 6.36; N, 9.14. Found: C,
C, SCH ), 29.5 (NCH ), 51.5 (C-3), 55.4 (2 × C, NCH ), 98.7–152.7
2
3
2
(
18 × C, ArC, C-2¢).
MS (ESI): m/z = 430.41 [M + H]+.
3
1
29
3
8
0.98; H, 6.38; N, 9.15.
Anal. Calcd for C H N OS: C, 72.69; H, 6.34; N, 9.78. Found: C,
26
27
3
7
2.69; H, 6.34; N, 9.81.
5
-Chloro-1,3,3-trimethyl-6¢-1,2,3,4-tetrahydroisoquinolino-
spiro(indoline-2,3¢-naphtho[2,1-b][1,4]oxazine) (9)
Mp 216–218 °C.
1
,3,3-Trimethyl-6¢-indolinospiro(indoline-2,3¢-naphtho[2,1-
b][1,4]oxazine) (6)
Mp 251–253 °C (Lit.1 231–233 °C).
5
IR (KBr): 3065, 2978, 2954, 1612, 1581, 1483, 1410, 1365, 1269,
1
–
1
239, 1161, 1030, 933, 893, 850, 810, 758 cm .
IR (KBr): 3048, 2965, 2848, 1588, 1481, 1409, 1355, 1300, 1243,
1
–1
1
162, 1138, 1097, 1019, 955, 876, 833, 772, 744, 702 cm .
H NMR (300 MHz, CDCl ): d = 1.35 [s, 6 H, C(CH ) ], 2.74 (s,
3
3 2
1
3 H, NCH
3
), 3.14 (m, 2 H, CH
2
), 3.41 (m, 2 H, CH
2
), 4.25 (s, 2 H,
H NMR (300 MHz, CDCl ): d = 1.36 [s, 6 H, C(CH ) ], 2.77 (s,
3
3 2
CH ), 6.47 (d, J = 8.2 Hz, 1 H, H-7), 6.69 (s, 1 H, H-5¢), 7.03, 7.07
2
3
H, NCH ), 3.18 (m, 2 H, CH ), 3.92 (m, 2 H, NCH ), 6.28 (d,
3
2
2
(
6
2 × d, J = 2.1, 6.6 Hz, 2 H, H-4, H-5¢¢), 7.18 (m, 4 H, H-4¢¢, H-6, H-
J = 8.0 Hz, 1 H, H-7¢¢), 6.56 (d, J = 7.7 Hz, 1 H, H-7), 6.73 (dd,
J = 7.3, 7.3 Hz, 1 H, H-5¢¢), 6.89 (m, 2 H, H-5, H-4¢¢), 6.93 (s, 1 H,
H-5¢), 7.07 (d, J = 7.0 Hz, 1 H, H-4), 7.18, 7.20 (2 × d, J = 8.0,
7
7
¢¢, H-7¢¢), 7.37 (ddd, J = 8.2, 8.1, 1.3 Hz, 1 H, H-8¢), 7.57 (ddd,
J = 8.2, 8.2, 1.3 Hz, 1 H, H-9¢), 7.62 (s, 1 H, H-2¢), 8.08 (d,
J = 8.2 Hz, 1 H, H-7¢), 8.58 (d, J = 8.0 Hz, 1 H, H-10¢).
.6 Hz, 2 H, H-6, H-6¢¢), 7.34 (ddd, J = 8.4, 8.2, 1.3 Hz, 1 H, H-8¢),
.59 (ddd, J = 8.1, 8.3, 1.3 Hz, 1 H, H-9¢), 7.69 (s, 1 H, H-2¢), 7.96
1
3
C NMR (75 MHz, CDCl ): d = 20.5 (CH ), 25.2 (CH ), 29.5
3
3
3
(
d, J = 8.0 Hz, 1 H, H-7¢), 8.61 (d, J = 8.4 Hz, 1 H, H-10¢).
(CH ), 29.7 (NCH ), 51.5 (C-3), 51.7 (NCH ), 54.9 (NCH ), 98.7–
162.2 (24 × C, ArC, C-2¢).
MS (ESI): m/z = 494.27 [M + H]+.
2 3 2 2
1
3
C NMR (75 MHz, CDCl ): d = 20.7 (CH ), 25.4 (CH ), 28.8
3
3
3
(
CH ), 29.6 (NCH ), 51.6 (C-3), 55.1 (NCH ), 98.7–162.2 (24 × C,
2
3
2
ArC, C-2¢).
MS (ESI): m/z = 446.51 [M + H]+.
Anal. Calcd for C H N O: C, 80.87; H, 6.11; N, 9.43. Found: C,
Anal. Calcd for C H ClN O: C, 75.37; H, 5.71; N, 8.51. Found: C,
75.26; H, 5.69; N, 8.53.
3
1
28
3
30
27
3
1
2
,3,3-Trimethyl-6¢-1,2,3,4-tetrahydroquinolinospiro(indoline-
,3¢-naphtho[2,1-b][1,4]oxazine) (10)
8
0.89; H, 6.14; N, 9.40.
Mp 182–184 °C.
5
-Chloro-1,3,3-trimethyl-6¢-indolinospiro(indoline-2,3¢-naph-
tho[2,1-b][1,4]oxazine) (7)
IR (KBr): 3061, 2960, 2867, 1596, 1487, 1452, 1404, 1357, 1295,
–
1
Mp 263–265 °C.
1243, 1194, 1159, 1099, 1027, 960, 857, 818, 745, 702 cm .
Synthesis 2010, No. 20, 3418–3422 © Thieme Stuttgart · New York

3
422
M.-L. Pang et al.
PAPER
1
H NMR (300 MHz, CDCl ): d = 1.35 (s, 3 H, CH ), 1.36 (s, 3 H, Acknowledgment
3
3
CH ), 2.12 (m, 2 H, CH ), 2.77 (s, 3 H, NCH ), 2.94 (m, 2 H, CH ),
3
2
3
2
We gratefully thank the National Natural Science Foundation of
China for financial support (grant no. 20971071 and 20602020).
3
.61 (m, 2 H, CH ), 6.11 (d, J = 7.7 Hz, 1 H, H-7¢¢), 6.56 (d,
2
J = 7.7 Hz, 1 H, H-7), 6.63 (dd, J = 7.3, 7.3 Hz, 1 H, H-5¢¢), 6.78
(
dd, J = 7.2, 7.2 Hz, 1 H, H-5), 6.87 (dd, J = 6.9, 6.9 Hz, 1 H, H-
4
7
¢¢), 6.90 (s, 1 H, H-5¢), 7.05 (m, 2 H, H-4, H-6), 7.20 (dd, J = 7.5,
.5 Hz, 1 H, H-6¢¢), 7.33 (ddd, J = 8.2, 8.1, 1.3 Hz, 1 H, H-8¢), 7.57
References
(
ddd, J = 8.2, 8.2, 1.3 Hz, 1 H, H-9¢), 7.72 (s, 1 H, H-2¢), 7.86 (d,
(
1) Ciardelli, F.; Fabbri, D.; Pieroni, O.; Fissi, A. J. Am. Chem.
Soc. 1989, 111, 3470.
J = 8.4 Hz, 1 H, H-7¢), 8.61 (d, J = 8.4 Hz, 1 H, H-10¢).
1
3
(2) Salemi-Delvaux, C.; Luccioni-Houze, B.; Baillet, G.; Giusti,
C NMR (75 MHz, CDCl ): d = 20.8 (CH ), 22.5 (CH ), 25.4
3
3
2
G.; Gugliemetti, R. J. Photochem. Photobiol., A 1995, 91,
(
CH ), 27.7 (CH ), 29.6 (NCH ), 51.5 (C-3), 51.7 (NCH ), 98.6–
3 2 3 2
223.
1
50.1 (24 × C, ArC, C-2¢).
(3) Ko, C. C.; Wu, L. X.; Wong, K. M. C.; Zhu, N. Y.; Yam, V.
MS (ESI): m/z = 460.46 [M + H]+.
W. W. Chem. Eur. J. 2004, 10, 766.
Anal. Calcd for C H N O: C, 81.02; H, 6.36; N, 9.14. Found: C,
(4) Inouye, M.; Ueno, M.; Kitao, T. J. Am. Chem. Soc. 1990,
112, 8977.
31
29
3
8
1.00; H, 6.32; N, 9.18.
(5) Inouye, M.; Noguchi, Y.; Isagawa, K. Angew. Chem., Int.
1
,3,3-Trimethyl-6¢-piperazinospiro(indoline-2,3¢-naphtho[2,1-
Ed. Engl. 1994, 33, 1163.
(6) Shinmori, H.; Takeuchi, M.; Shinkai, S. J. Chem. Soc.,
Perkin Trans. 2 1996, 1.
b][1,4]oxazine) (11)
Mp >300 °C.
(
7) Inouye, M.; Akamatsu, K.; Nakazumi, H. J. Am. Chem. Soc.
1997, 119, 9160.
8) Dagan, M. L.; Katz, E.; Willner, I. J. Chem. Soc., Chem.
Commun. 1994, 2741.
IR (KBr): 3056, 2960, 2814, 1612, 1587, 1484, 1453, 1408, 1361,
–
1
1
298, 1270, 1197, 1137, 1026, 963, 898, 847, 762, 737 cm .
(
1
H NMR (300 MHz, CDCl ): d = 1.35 (s, 3 H, CH ), 1.36 (s, 3 H,
3
3
CH ), 2.75 (s, 3 H, NCH ), 3.05 (m, 4 H, 2 × CH ), 3.14 (m, 4 H, 2
×
3
3
2
(9) Blonder, R.; Katz, E.; Willner, I.; Wray, V.; Buckmann, A.
F. J. Am. Chem. Soc. 1997, 119, 11747.
10) Willner, I. Acc. Chem. Res. 1997, 30, 347.
11) Willner, I.; Rubin, S.; Shatzmiller, R.; Zor, T. J. Am. Chem.
Soc. 1993, 115, 8690.
CH ), 6.57 (d, J = 7.8 Hz, 1 H, H-7), 6.60 (s, 1 H, H-5¢), 6.89 (dd,
2
J = 7.3, 7.4 Hz, 1 H, H-5), 7.10 (d, J = 7.2 Hz, 1 H, H-4), 7.20 (ddd,
J = 7.7, 7.6, 1.3 Hz, 1 H, H-6), 7.38 (ddd, J = 8.2, 8.2, 1.3 Hz, 1 H,
H-8¢), 7.56 (ddd, J = 8.2, 8.2, 1.3 Hz, 1 H, H-9¢), 7.63 (s, 1 H, H-2¢),
(
(
8
.04 (d, J = 8.4 Hz, 1 H, H-7¢), 8.55 (d, J = 8.4 Hz, 1 H, H-10¢).
(
12) Chu, N. Y. C. Can. J. Chem. 1983, 61, 300.
(13) Tan, T. F.; Chen, P. L.; Huang, H. M.; Meng, J. B.
1
3
C NMR (75 MHz, CDCl ): d = 20.5 (CH ), 25.3 (CH ), 29.5
3
3
3
Tetrahedron 2005, 61, 8192.
(
1
NCH ), 45.6 (2 × C, CH ), 54.2 (2 × C, CH ), 51.4 (C-3), 98.6–
52.1 (18 × C, ArC, C-2¢).
3
2
2
(
(
14) Lokshin, V.; Samat, A.; Metelitsa, A. V. Russ. Chem. Rev.
2002, 71, 893.
MS (ESI): m/z = 413.38 [M + H]+.
15) Rickwood, M.; Marsden, S. D.; Ormsby, M. E.; Staunton, A.
L.; Wood, D. W. Mol. Cryst. Liq. Cryst. Sci. Technol., Sect.
A 1994, 246, 17.
Anal. Calcd for C H N O: C, 75.70; H, 6.84; N, 13.58. Found: C,
26
28
4
7
5.67; H, 6.81; N, 13.63.
(16) Koshkin, A. V.; Lokshin, V.; Samat, A.; Gromov, S. P.;
Fedorova, O. A. Synthesis 2005, 1876.
Synthesis 2010, No. 20, 3418–3422 © Thieme Stuttgart · New York