Microwave-Assisted Solvent-Free Synthesis of the Substituted Spiroindolinonaphth[2,1-b][1,4]oxazines

Article abstract of DOI:10.1081/SCC-120027269

The synthesis of the substituted spiroindolinonaphth[2,1-b][1,4]oxazines 3a-e is developed through the condensation of 2-methylene-1,3,3-trimethylindoline derivatives and 1-nitroso-2-naphthol under microwave irradiation. In the same conditions, in presence of morpholine the 6′-morpholinosubstituted compounds 4a, b, d, e are formed. The main advantages of the method are the short reaction time, solvent-free reaction condition, cleaner reaction products and the higher product yields in comparison with known methods of synthesis.

Full text of DOI:10.1081/SCC-120027269

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Microwave-Assisted Solvent-Free Synthesis of the
Substituted Spiroindolinonaphth[2,1-b][1,4]oxazines
a
a
b
b
c
A. V. Koshkin , O. A. Fedorova , V. Lokshin , R. Guglielmetti , J. Hamelin , F.
c
a
Texier-Boullet & S. P. Gromov
a
Center of Photochemistry of the Russian Academy of Sciences , Novatorov Str. 7a,
19421, Moscow, Russia
1
b
Faculté des Sciences de Luminy , Université de la Méditerraneé , Marseille, France
c
Synthèse et Electrosynthèse Organique 3 , Université de Rennes 1 , Campus de
Beaulieu, Rennes, France
Published online: 18 Oct 2011.
To cite this article: A. V. Koshkin , O. A. Fedorova , V. Lokshin , R. Guglielmetti , J. Hamelin , F. Texier-Boullet & S. P.
Gromov (2004) Microwave-Assisted Solvent-Free Synthesis of the Substituted Spiroindolinonaphth[2,1-b][1,4]oxazines,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:2,
315-322, DOI: 10.1081/SCC-120027269
To link to this article: http://dx.doi.org/10.1081/SCC-120027269
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w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 2, pp. 315–322, 2004
Microwave-Assisted Solvent-Free
Synthesis of the Substituted
Spiroindolinonaphth[2,1-b][1,4]oxazines
1
A. V. Koshkin, O. A. Fedorova, V. Lokshin,
1,*
2
2
R. Guglielmetti, J. Hamelin, F. Texier-Boullet,
3
3
1
and S. P. Gromov
1
2
Center of Photochemistry of the Russian Academy of Sciences,
Moscow, Russia
Facult e´ des Sciences de Luminy, Universit e´ de la M e´ diterrane e´ ,
Marseille, France
3
Synth e` se et Electrosynth e` se Organique 3, Universit e´ de Rennes 1,
Campus de Beaulieu, Rennes, France
ABSTRACT
The synthesis of the substituted spiroindolinonaphth[2,1-b][1,4]oxazines
a–e is developed through the condensation of 2-methylene-1,3,3-
trimethylindoline derivatives and 1-nitroso-2-naphthol under microwave
3
irradiation. In the same conditions, in presence of morpholine the
0
6
-morpholinosubstituted compounds 4a, b, d, e are formed. The main
*
Correspondence: O. A. Fedorova, Center of Photochemistry of the Russian Academy
of Sciences, Novatorov Str. 7a, 119421 Moscow, Russia; E-mail: fedorova@
photonics.ru.
3
15
DOI: 10.1081/SCC-120027269
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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3
16
Koshkin et al.
advantages of the method are the short reaction time, solvent-free reaction
condition, cleaner reaction products and the higher product yields in
comparison with known methods of synthesis.
Key Words: Microwave irradiation; Spirooxazines; Solvent-free
synthesis.
Among many classes of organic photochromic compounds, spirooxazines
have been proven to be one of the most useful due to possible practical
[
1a,b]
applications.
able depth of photoactivated coloration and generally to relatively large
The aminosubsitution of spirooxazines gives rise to remark-
[
2]
hypsochromic color shifts. By now, the widely applied method to synthesize
the spironaphthoxazines consists in the condensation of methylenic base with
[
3]
1
-nitroso-2-naphthol. The reaction leads generally to low yields of spiro-
compounds even if optimization of experimental conditions allowed to
[
4]
improve them in some case.
The same reaction of the respective 2-methyleneindoline with 4-
morpholino-1-nitroso-2-naphthol being formed in situ from the reaction of
1-oximino-naphthoquinone (tautomeric form of 1-nitroso-2-naphthol) with a
morpholine, results in the formation of 6 -morpholino spirooxazines (method
0
[5]
developed by Rickwood et al.) The general synthetic scope of method is
rather limited by low yield for the spiro compound and by the lack of reactivity
of the 2-methyleneindolines containing electronegative substituted groups.
Otherwise, the advantages of the approach are the simplicity and the possibil-
ity to avoid the preliminary synthesis of the 4-amino substituted 1-nitroso-2-
[
2,5]
naphthols.
In the present paper, in order to improve the reaction condensation of
-methylene-1,3,3-trimethylindoline derivatives 1a–e with 1-nitroso-2-
2
naphthol with (reaction B) or without the presence of morpholine (reaction
A), the effect of microwave irradiations has been studied (Sch. 1). It is
known, that reactions promoted by microwave irradiation have received
considerable attention because of their high efficiency, convenient work-up
conditions. Several reactions of synthetic importance such as alkylation,
condensation, oxidation etc., have been satisfactorily done under microwave
[
6a–f]
irradiation.
In a typical reaction, the equimolar mixture of 1-nitrosonaphthol 2 with
indoline derivatives 1a–e was irradiated in a microwave oven Synthewave
w[6f]
402
for 15 min to produce 3a–e. In the same reaction in presence of
morpholine the compounds 4a, b, d, e were formed. The temperature of the
reactions, yields of the products are summarized in Table 1. The bases 1d, e
were generated in situ from corresponding salts by addition of Et N. It was
3

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Microwave-Assisted Solvent-Free Synthesis
317
Scheme 1.
observed that 3a forms with practically the same yields from 1a or
hydroperchlorate of 1a in presence of Et N (Table 1). The spirooxazine 3a–e
3
[7]
yields obtained according to the known method (heating in EtOH) are given
in Table 1 for comparison. For compounds 4a, b, d, e the yields obtained by
[5]
method developed by M. Rickwood et al. are also indicated.
Regarding the data presented in Table 1, it can be concluded that the
yields obtained by new reaction A are always higher than those in classic
heating, and moreover, the compounds formed are much clean. It is
important to note that the studied method can be applied to a large set of
substitutions.
The results obtained in the case of the reaction B demonstrated the
0
success in carrying out the one-pot synthesis of 6 -morpholino substituted
spironaphthoxazines with mild yields. The method failed only in case of
compound 1c, containing the strong acceptor nitro group. In contrast, in
comparison with reaction developed by M. Rickwood et al. the improved yield
is observed in all cases.
Thus, a simple method using a dry media and short time of reaction has
been described to synthesize substituted spironaphthoxazines. The obtained
compounds were cleaner and formed with higher yields compared to the usual
methods of condensation.

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18
Koshkin et al.

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Microwave-Assisted Solvent-Free Synthesis
EXPERIMENTAL
319
1
H NMR spectra were recorded on Bruker BM 250 P spectrometer
250 MHz). Chemical shifts are expressed in parts per million downfield from
(
tetramethylsilane as an internal standard. CDCl was used as solvent for all
probes.
3
Thin-layer chromatography (TLC) were performed on 0.2-mm precoated
plates of Silica gel 60 F-254 (Merck). Visualization was made with ultraviolet
light (254 and 365 nm). For preparative column chromatography was used
silica gel 60 Merck with 0.043–0.060 mm particles.
Reactions under microwave irradiation were performed in a Prolabo
w
Synthewave 402 (2.45 GHz) monomode microwave reactor, the reaction
temperature was monitored at the values given in Table 1 by means of an IR-
[
6f]
captor. All solvents and reagents were purchased from Acros Organics and
Aldrich Chimie and used without further purification.
Reaction A. A mixture of 1 mmol of indoline compound (1a–e) and
1
mmol of 1-nitroso-2-naphthol in a vessel (Ø ¼ 1 cm) was heated for 3 min to
reach the reaction temperature in the microwave oven. Reaction temperature
was indicated in Table 1. If the bases were generated in situ from correspond-
ing salts 1.5 equivalent of Et N are added per acid equivalent. The vessel was
3
irradiated at the reaction temperature for 12 min under continuous stirring.
After the reaction, the product was purified by column chromatography on
silica gel (pentane-diethyl ether mixtures from 100 : 1 to 1 : 1 were used as
eluents). The yields of the prepared compounds 3a–e are indicated in Table 1.
0
3]
1
,3,3-Trimethylspiro[indolino-2,3 -[3H]naphth[2,1-b]oxazine] (3a).
[
m.p. 1258C, lit. 125–1278C.
-Chloro-1,3,3-trimethylspiro[indolino-2,3 -[3H]naphth[2,1-b]oxa-
0
5
[4]
zine] (3b). m.p.174–1768C, lit. 177–1788C.
0
-Nitro-1,3,3-trimethylspiro[indolino-2,3 -[3H]naphth[2,1-b]oxazine]
5
[
7]
(
3c). m.p. 2258C, lit. 2258C.
-Methoxy-1,3,3-trimethylspiro[indolino-2,3 -[3H]naphth[2,1-b]oxa-
0
5
[4]
zine] (3d). m.p. 128–1318C, lit. 130–1328C.
,3-Dimethyl-1-hexadecylspiro[indolino-2,3 -[3H]naphth[2,1-b]oxa-
0
3
1
zine] (3e). m.p. 56–578C. H NMR (d, ppm, J, Hz) 0.88 (t, 3H, J ¼ 7.5,
CH ), 1.22 (m, 26H, 13CH ), 1.33 (s, 3H, CH ), 1.35 (s, 3H, CH ), 1.65 (m,
3
2
3
3
2
H, CH ), 3,17 (s, 2H, N–CH ), 6.59 (d, 1H, J ¼ 7.7, H-7), 6.87 (dd, 1H,
2
2
0
J ¼ 7.4 and 7.3, H-5), 6.99 (d, 1H, J ¼ 8.8, H-5 ), 7.08 (d, 1H, J ¼ 7.1, H-4),
.20 (ddd, 1H, J ¼ 7.6, 7.4 and 1.2, H-6), 7.39 (ddd, 1H, J ¼ 7.6, 7.5 and 1.2,
7
0
0
0
0
H-8 ), 7.57 (ddd, 1H, J ¼ 7.5, 7.5 and 1.2, H-9 ), 7.66 (d, 1H, J ¼ 8.8, H-6 ),
0
0
7
.73 (s, 1H, H-2 ), 7.74 (d, 1H, J ¼ 8.4, H-7 ), 8.54 (d, 1H, J ¼ 8.4, H-10 ).
Anal. Calcd for C H N O: C, 82.48; H, 9.35; N, 5.20. Found: C, 82.63; H,
3
7 50 2
9.91; N, 5.05.

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20
Koshkin et al.
Reaction B. A mixture of 1 mmol of indoline compound 1a–e, 1 mmol
of 1-nitroso-2-napthol and 1 mmol of morpholine in a vessel ([ ¼ 1 cm) was
heated for 3 min to the reaction temperature in the microwave oven. Reaction
temperature was indicated in Table 1. If the bases were generated in situ from
corresponding salts 1.5 equivalent of Et N are added per acid equivalent. The
3
vessel was irradiated at the reaction temperature for 12 min under continuous
stirring. After the reaction, the product was purified by column chromatogra-
phy on silica gel, pentane-diethyl ether mixtures from 100 : 1 to 1 : 1 were used
as eluents. The yields of the prepared compounds 4a, b, d, e are indicated in
Table 1.
0
0
6
-Morpholino-1,3,3-trimethylspiro[indolino-2,3 -[3H]naphth[2,1-b]
[5]
oxazine] (4a). m.p. 198–2008C, lit. 1968C.
0
0
5
-Chloro-6 -morpholino-1,3,3-trimethylspiro[indolino-2,3 -[3H]
1
naphth[2,1-b]oxazine] (4b). m.p. 205–2078C, lit. 1968C. H NMR (d,
ppm, J, Hz) 1.34 (s, 6H, C(CH ) ), 2.73 (s, 3H, N–CH ), 3.08 (m, 4H,
[2]
3
2
3
N(CH ) ), 3.95 (m, 4H, O(CH ) ), 6.48 (d, 1H, J ¼ 8.2, H-7), 6.60 (s, 1H, H-
2
2
2 2
0
5
1
), 7.04 (d, 1H, J ¼ 2.0, H-4), 7.16 (dd, 1H, J ¼ 8.2 and 2.2, H-6), 7.39 (ddd,
0
0
H, J ¼ 8.2, 8.2 and 1.2, H-8 ), 7.57 (ddd, 1H, J ¼ 8.2, 8.2 and 1.2, H-9 ), 7.62
0
0
0
(
Calcd for C H ClN O : C, 69.71; H, 5.85; N, 9.38. Found: C, 69.63; H, 5.91;
s, 1H, H-2 ), 8.05 (d, 1H, J ¼ 8.1, H-7 ), 8.55 (d, 1H, J ¼ 8.4, H-10 ). Anal.
2
6
26
3 2
N, 9.35.
-Methoxy-6 -morpholino-1,3,3-trimethylspiro[indolino-2,3 -[3H]
0
0
5
[2]
1
naphth[2,1-b]oxazine] (4d). m.p 170–1728C, lit. 172–1738C. H NMR
(
d, ppm, J, Hz) 1.35 (s, 3H, CH ), 1.36 (s, 3H, CH ), 2.70 (s, 3H, N–CH ),
3 3 3
3
.06 (m, 4H, N(CH ) ), 3.80 (s, 3H, OCH ), 3.94 (m, 4H, O(CH ) ), 6.48
2 2 3 2 2
0
(
d, 1H, J ¼ 8.7, H-7), 6.63 (s, 1H, H-5 ), 6.74 (m, 2H, H-4, H-6), 7.38 (dd,
0
0
1
H, J ¼ 7.2 and 7.8, H-8 ), 7.57 (dd, 1H, J ¼ 7.6 and 7.3, H-9 ), 7.64 (s, 1H,
0
0
0
H-2 ), 8.05 (d, 1H, J ¼ 8.3, H-7 ), 8.55 (d, 1H, J ¼ 8.6, H-10 ). Anal. Calcd
for C H N O : C, 73.11; H, 6.59; N, 9.47. Found: C, 73.01; H, 6.68; N,
2
7 29 3 3
9
.39.
0 0
,3-Dimethyl-1-hexadecyl-6 -morpholinospiro[indolino-2,3 -[3H]
3
1
naphth[2,1-b]oxazine] (4e). violet oil. H NMR (d, ppm, J, Hz) 0.88 (t, 3H,
J ¼ 6.5, CH ), 1.23 (m, 26H, 13CH ), 1.34 (s, 6H, C(CH ) ), 1.63 (m, 2H,
3
2
3 2
CH ), 3.07 (m, 4H, N(CH ) ), 3.14 (t, 2H, J ¼ 7.5, N–CH ), 3.95 (m, 4H,
2
2 2
2
0
O(CH ) ), 6.59 (m, 2H, H-5 and H-7), 6.87 (dd, 1H, J ¼ 7.3 and 7.4, H-5),
2
2
7
.08 (d, 1H, J ¼ 7.1, H-4), 7.19 (dd, 1H, J ¼ 7.6 and 7.6, H-6), 7.38 (ddd, 1H,
0
0
J ¼ 8.2, 8.2 and 1.3, H-8 ), 7.55 (ddd, 1H, J ¼ 8.4, 8.1 and 1.3, H-9 ), 7.65
0
0
0
(
Calcd for C H N O : C, 78.93; H, 9.21; N, 6.73. Found: C, 78.84; H, 9.30;
s, 1H, H-2 ), 8.04 (d, 1H, J ¼ 8.1, H-7 ), 8.54 (d, 1H, J ¼ 8.4, H-10 ). Anal.
4
1 57 3 2
N, 6.69.

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Microwave-Assisted Solvent-Free Synthesis
ACKNOWLEDGMENT
321
The study was supported by the INTAS (Grant 97-31193 and YSF 2001/
-180), PICS 705, RFBR (Grant 02-03-33058) and Russian Academy of
2
Sciences.
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Received in the UK April 30, 2003

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