Synthesis of highly functionalized oxazines by Vilsmeier cyclization of amidoalkyl naphthols

Article abstract of DOI:10.1016/j.tetlet.2009.07.051

The intramolecular cyclization of amidoalkyl naphthols by Vilsmeier reagent produced 1,3-oxazines. The Vilsmeier reagent (chloromethylenedimethylammonium chloride) has been used as an efficient and cheap acid activator for the one-step synthesis of oxazin

Full text of DOI:10.1016/j.tetlet.2009.07.051

Tetrahedron Letters 50 (2009) 5474–5478
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of highly functionalized oxazines by Vilsmeier cyclization
of amidoalkyl naphthols
*
M. Damodiran, N. Panneer Selvam, Paramasivan T. Perumal
Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai 600 020, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The intramolecular cyclization of amidoalkyl naphthols by Vilsmeier reagent produced 1,3-oxazines. The
Vilsmeier reagent (chloromethylenedimethylammonium chloride) has been used as an efficient and
cheap acid activator for the one-step synthesis of oxazine derivatives. A mechanism involving sequential
haloformylation and intramolecular nucleophilic cyclization is proposed.
Received 23 May 2009
Revised 7 July 2009
Accepted 10 July 2009
Available online 15 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
The synthesis of 1,3-oxazines has attracted attention in the past
because of their potential as antibiotics,1a–d antitumor agents,1e–g
analgesics,1h,i and anticonvulsants.1j 1,3-Oxazines have generated
great interest as anti-psychotic agents and as possible effectors
for serotonin and dopamine receptors.2 In addition, benzo-1,3-oxa-
zines are known to be biologically active as anti-malarial,3a anti-
anginal ,3b anti-hypertensive 3c and potent anti-rheumatic agents.3d
Several methods for the preparations of 1,3-oxazine derivatives
have previously been reported.4 The ring-chain tautomeric inter-
conversion of N-unsubstituted 1,3-N-O-heterocycles and the corre-
ier–Haack reactions of amidoalkyl naphthols. To the best of our
knowledge, the highly functionalized system (2) is unknown in
the literature, which provided the impetus to synthesize these no-
vel compounds.
Initially, we synthesized amidoalkyl naphthols based on re-
ported procedure.19 The synthesized amidoalkyl naphthols were
treated with Vilsmeier reagent to give oxazine derivatives.
To begin our study, compound 1b was treated with Vilsmeier
reagent (DMF 12 equiv, POCl3 8 equiv)20 at room temperature.
The resulting mixture quickly became a viscous liquid, but no
product was detected by TLC. When the resulting mixture was
heated at 90 °C for about 3 h the reaction proceeded smoothly
and the product was formed as indicated by TLC. After complete
consumption of the starting materials, the mixture was poured
into ice and neutralized with sodium acetate. The crude compound
was extracted with chloroform and washed with water. The organ-
ic layer was dried over anhydrous sodium sulfate and concentrated
under reduced pressure. The crude product was purified by column
chromatography (Scheme 1, Table 1, entry 2).
sponding
hydroxyalkylimines
can
often
be
exploited
advantageously in different areas of organic synthesis and also in
physical, medicinal and peptide chemistry.5 Hence, the synthesis
of these derivatives is of considerable interest.
The Vilsmeier–Haack reagent is an efficient, economical and
mild reagent for the formylation of reactive aromatic and heteroar-
omatic substrates.6 It is now used as a powerful synthetic tool for
the construction of many heterocyclic compounds.7 The classical
Vilsmeier–Haack reaction, however, involves electrophilic substi-
tution of an activated aromatic ring with a halomethyleniminium
salt to yield the corresponding iminium species, which facilitates
easy entry into various nitrogen- and oxygen-based heterocy-
cles.8,7a,d Vilsmeier reagent serves not only as a formylating agent,9
but also as an activating reagent for carboxylic acids to give es-
ters,10 amides11 and acid chlorides,12 and for alcohols to give alkyl
chlorides,13 esters,14 alkyl aryl sulfides15 and imides.16
In our previous work, we have demonstrated the utility of the
Vilsmeier reagent in the synthesis of functionalized heterocy-
cles.17,6c In connection with our interest in the synthesis of highly
valuable heterocycles,18 herein we report a convenient and effi-
cient synthesis of highly functionalized oxazines via the Vilsme-
The structures of compounds 2a–i were confirmed by IR, 1H and
13C NMR spectroscopy, mass spectrometry and elemental analysis.
The mass spectrum of 2b displayed the molecular ion (M+1) peak
R
O
R
DMF/POCl3
3h, 90 o
R1
C
N
H
NH
R2
OH
1a-o
R1 = H, CH3, Ph
O
CHO
2a-o
R2 = CH3, Ph, CHO
* Corresponding author. Tel.: +91 44 24911329; fax: +91 44 24911539.
E-mail address: ptperumal@gmail.com (P.T. Perumal).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.051

M. Damodiran et al. / Tetrahedron Letters 50 (2009) 5474–5478
5475
Table 1
Synthesis of oxazine derivatives using Vilsmeier reagent
Entry
Amidoalkyl naphthols
Producta (2)
Time (h)
3
Yieldb (%)
Ph
NHAc
NH
1
86
CHO
O
OH
CHO
1a
2a
Ph-m-NO2
NH
NHAc
NO2
2
3
3
3
3
3
3
3
3
3
3
3
90
90
85
78
76
75
82
74
75
CHO
O
OH
2b
1b
CHO
Ph-p-NO2
NH
NHAc
OH
CHO
O
NO2
2c
2d
1c
CHO
Ph-p-Cl
NHAc
OH
NH
4
CHO
CHO
Cl
O
1d
Ph-p,m-Cl
NHAc
OH
Cl
NH
5
CHO
Cl
O
1e
CHO
2e
2f
Ph-p-Me
NH
NHAc
OH
6
CHO
O
1f
CHO
Ph-p-OMe
NHAc
OH
NH
7
CHO
OMe
O
1g
CHO
2g
2h
Ph-p-Br
NHAc
NH
8
CHO
CHO
OH
Br
O
1h
1i
NHAc
Ph-o-Cl
NH
Cl
9
CHO
O
OH
CHO
2i
O
Ph
O
HN
NH
10
11
OH
O
CHO
2j
1j
Ph-o-NO2
NH
NO2
HN
85
O
CHO
OH
2k
(continued on next page)
1k

5476
M. Damodiran et al. / Tetrahedron Letters 50 (2009) 5474–5478
Table 1 (continued)
Entry
Amidoalkyl naphthols
Producta (2)
Time (h)
Yieldb (%)
O
Ph
Ph
HN
NH
12
13
14
3
70
Ph
O
OH
CHO
2l
1l
O
Ph
Ph-o-NO2
NH
NO2
HN
3
3
3
80
75
81
Ph
O
CHO
OH
2m
1m
Ph
NHAc
NH
CHO
O
OH
CHO
1n
2n
Ph-m-NO2
NH
NHAc
NO2
15
CHO
O
OH
1o
2o
CHO
a
All compounds were characterized by 1H NMR, 13C NMR, IR, mass spectrometry and elemental analysis.
Isolated yield.
b
at m/z 375. The 1H NMR spectrum of 2b exhibited two singlets due
series of oxazine derivatives were synthesized and characterized
(Table 1, entries 1–9). All the prepared compounds gave good to
excellent yields (75–90%).
to –CHO and –NH protons at d 9.78 and d 11.84 (D2O exchange-
able). Signals at d 50.3 (benzylic carbon) and d 186.7 (–C@O) in
the 13C NMR spectrum confirmed the formation of the product. Fi-
nally, the structure 2b was confirmed by single-crystal X-ray dif-
fraction data (Fig. 1).21 To investigate the scope of this reaction, a
To further investigate the scope and generality of this method-
ology, a variety of amidoalkyl naphthols 1j–m and amidoalkyl
phenols 1n–o were employed (Table 1, 2j–o). It was observed that
under optimized reaction conditions,20 various amidoalkyl naph-
thols and amidoalkyl phenols reacted with Vilsmeier reagent to af-
ford a series of substituted oxazines in good yields. The reaction
was amenable to a wide range of amidoalkyl naphthols and amid-
oalkyl phenols. The results are summarized in Table 1 (entries 10–
15). The structures of compounds 2j–o were confirmed by IR, 1H
and 13C NMR spectroscopy, mass spectrometry and elemental
analysis.
A plausible mechanism for the synthesis of substituted oxa-
zines 2a is presented in Scheme 2. The in situ formation of
the chloromethyleniminium intermediate
A
(derived from
POCl3–DMF) is responsible for the formylation. The enolizable
ketone moiety of amidoalkyl naphthol derivative 1a readily re-
acts with chloromethylenedimethylammonium chloride interme-
diate at the active methylene position of
2 to yield the
intermediate 3, which undergoes dehydrochlorination to form
intermediate 4. The latter undergoes cyclization to intermediate
5, which spontaneously undergoes dehydroxylation to form the
intermediate 6. Attack of another Vilsmeier intermediate to 6
leads to the formation of intermediate 7. Hydrolysis of 7 gives
the product 2a.
In conclusion, we have reported the first example of the use
of the Vilsmeier reagent for the synthesis of oxazine derivatives
from amidoalkyl naphthols. The results shown above demon-
strated the efficiency and synthetic interests of the cyclization
reaction with respect to amidoalkyl naphthols 1 bearing various
amide groups. Furthermore, the scope of this reaction was ex-
plored with different substrates and the reactivity of its hetero-
cyclic products was investigated via further diversification.
Figure 1. ORTEP diagram of compound 2b.

M. Damodiran et al. / Tetrahedron Letters 50 (2009) 5474–5478
5477
O
P
Me
Me
Cl
H
O
Me
Me
-
N+
Cl
Cl
O
PO2Cl2
+ POCl3
Cl
N
H
..
N
H
Me
A
Me
+
..
Ph
O
Ph
OH
.
.
OH
Ph
..
N
H
H
N
Me
N+
Me
..
H
N
H
CH3
N
H
CH2
Cl
CH3
CH3
Cl
OH
OH
OH
A
3
1a
2
-HCl
Ph
O
+
O
Ph
..
NH
H
Ph
Me
N+
Me
H
..
N
H
NH
OH
-OH
CH3
CH3
..
O
Cl
N
OH
A
..
..
6
NMe2
+
5
4
NMe2
..
Ph
O
+
Ph
Ph
O
NH
Cl
+
+
..
NH
NH
NMe2
..
NMe2
-HCl
H
NMe2
O
NMe2
+
NMe2
NMe2
7
+
+
H2O
Ph
NH
H
O
O
O
H
2a
Scheme 2. Mechanism for the formation of 1,3-oxazine derivatives by Vilsmeier cyclization of amidoalkyl naphthols.
5. (a) Valters, R. E.; Fülöp, F.; Korbonits, D. Adv. Heterocycl. Chem. 1996, 66, 1; (b)
Lázár, L.; Fülöp, F. Eur. J. Org. Chem. 2003, 3025.
Acknowledgements
6. (a) Meth-Cohn, O.; Narine, A. B. Tetrahedron Lett. 1978, 23, 2045; (b) Khan, A. K.;
Shoeb, A. Indian J. Chem., Sect. B 1985, 24, 62.
One of the authors, M.D. thanks UGC and CSIR (New Delhi) for
the award of Senior Research Fellowship. The authors are thankful
to SAIF-IIT Madras for single-crystal X-ray diffraction analysis.
7. (a) Meth-Cohn, O. Heterocycles 1993, 35, 539; (b) Guzman, A.; Ronero, M.;
Maddox, M. L.; Machowski, J. M. J. Org. Chem. 1990, 55, 5793; (c) Sreenivasulu,
M.; Rao, K. G. S. Indian J. Chem., Sect. B 1989, 28, 584; (d) Mahata, P. K.;
Venkatesh, C.; Syam Kumar, U. K.; Ila, H.; Junjappa, H. J. Org. Chem. 2003, 68,
3966; (e) Chupp, J. P.; Metz, S. J. Heterocycl. Chem. 1979, 16, 65; (f) Katrtizky, A.
R.; Arend, M. J. Org. Chem. 1998, 63, 9989.
References and notes
8. (a) Lilienkampf, A.; Johansson, M. P.; Wähälä, K. Org. Lett. 2003, 5, 3387; (b)
Tang, X.-Y.; Shi, M. J. Org. Chem. 2008, 73, 8317; (c) Perumal, P. T. Indian J.
Heterocycl. Chem. 2001, 11, 1; (d) Pan, W.; Dong, D.-W.; Liu, Q. Org. Lett. 2007, 9,
2421; (e) Wang, K.-W.; Xiang, D.-X.; Dong, D.-W. Org. Lett. 2008, 10, 1691; (f)
Jones, G.; Stanforth, S. P. Org. React. 2000, 56, 355; (g) Marson, C. M. Tetrahedron
1992, 48, 3659; (h) Chen, L.; Zhao, Y.-L.; Liu, Q.; Cheng, C.; Piao, C.-R. J. Org.
Chem. 2007, 72, 9259; (i) Zhang, R.; Zhang, D.; Guo, Y.; Zhou, G.; Jiang, Z.; Dong,
D. J. Org. Chem. 2008, 73, 9504; (j) Wuts, P. G. M.; Northuis, J. M.; Kwan, T. A. J.
Org. Chem. 2000, 65, 9223; (k) Xiang, D.; Yang, Y.; Zhang, R.; Liang, Y.; Pan, W.;
Huang, J.; Dong, D. D. J. Org. Chem. 2007, 72, 8593.
9. (a) Campaigne, E.; Archer, W. L. J. Am. Chem. Soc. 1953, 75, 989; (b) Treihs, W.;
Neupert, H. J.; Hiebsch J. Chem. Ber. 1959, 92, 141.
10. (a) Procopiou, P. A.; Brodie, A. C.; Deal, M. J.; Hayman, D. F. Tetrahedron Lett.
1993, 34, 7483; (b) Procopiou, P. A.; Brodie, A. C.; Deal, M. J.; Hayman, D. F. J.
Chem. Soc., Perkin Trans. 1 1996, 2249.
1. (a) Haneishi, T.; Okazaki, T.; Hata, T.; Tamura, C.; Nomura, M.; Naito, A.; Seki, I.;
Arai, M. J. Antibiot. 1971, 24, 797; (b) Sasaki, K.; Kusakabe, Y.; Esumi, S. J.
Antibiot. 1972, 25, 151; (c) Kusakabe, Y.; Nagatsu, J.; Shibuya, M.; Kawaguchi,
O.; Hirose, C.; Shirato, S. J. Antibiot. 1972, 25, 44; (d) Kupchan, S. M.; Komoda, Y.;
Court, W. A.; Thomas, G. J.; Smith, R. M.; Karim, A.; Gilmore, C. J.; Haltivanger, R.
C.; Bryan, R. F. J. Am. Chem. Soc. 1972, 94, 1354; (e) Wani, M. C.; Taylor, H. L.;
Wall, M. E. J. Chem. Soc., Chem. Commun. 1973, 390; (f) Johnson, P. Y.; Silver, R. B.
J. Heterocycl. Chem. 1975, 10, 1029; (g) Renullard, S.; Rebhun, L. I.; Havic, G. A.;
´
´
Kupchan, S. M. Science 1975, 189, 1002; (h) Urbanski, T.; Ghrne, D.; Szczerek, I.;
Modaski, M. Polish Patent 1967, 54, 007; (i) Lesher, G. Y.; Surrey, A. R. J. Am.
Chem. Soc. 1955, 77, 636; (j) Mosher, H. S.; Frankel, M. B.; Gregory, M. J. Am.
Chem. Soc. 1953, 75, 5326.
2. Peglion, J. L.; Vian, J.; Gourment, B.; Despaux, N.; Audinot, V.; Millan, M. Bioorg.
Med. Chem. Lett. 1997, 7, 881.
3. (a) Ren, H.; Grady, S.; Gamenara, D.; Heinzen, H.; Moyna, P.; Croft, S.; Kendrick,
H.; Yardley, V.; Moyna, G. Bioorg. Med. Chem. Lett. 2001, 11, 1851; (b) Benedini,
F.; Bertolini, G.; Cereda, R.; Doná, G.; Gromo, G.; Levi, S.; Mizrahi, J.; Sala, A. J.
Med. Chem. 1995, 38, 130; (c) Clark, R. D.; Caroon, J. M.; Kluge, A. F.; Repke, D.
B.; Roszkowski, A. P.; Strosberg, A. M.; Baker, S.; Bitter, S. M.; Okada, M. D. J.
Med. Chem. 1983, 26, 657; (d) Matsuoka, H.; Ohi, N.; Mihara, M.; Suzuki, H.;
Miyamoto, K.; Maruyama, N.; Tsuji, K.; Kato, N.; Akimoto, T.; Takeda, Y.; Yano,
K.; Kuroki, T. J. Med. Chem. 1997, 40, 105.
11. Zaoral, M.; Arnold, Z. Tetrahedron Lett. 1960, 1, 9.
12. Eilingsfeld, H.; Seefelder, M.; Weidinger, H. Angew. Chem. 1960, 72, 836.
13. Hepburn, D. R.; Hudson, H. R. J. Chem. Soc., Perkin Trans. 1 1976, 754.
14. (a) Barrett, A. G. M.; Braddock, D. C.; James, R. A.; Koike, N.; Procopiou, P. A. J.
Org. Chem. 1998, 63, 6273; (b) Barrett, A. G. M.; Koike, N.; Procopiou, P. A. Chem.
Commun. 1995, 1403.
15. Kawano, Y.; Kaneko, N.; Mukaiyama, T. Chem. Lett. 2005, 34, 1612.
16. Barrett, A. G. M.; Braddock, D. C.; James, R. A.; Procopiou, A. Chem. Commun.
1997, 433.
4. (a) Sainsbury, M.. In Comprehensive Heterocyclic Chemistry; Boulton, A. J.,
Mckillop, A., Eds.; Pergamon Press: Canada, 1984; Vol. 3, p 995. Part 2B; (b)
Khumtaveeporn, K.; Alper, H. J. Org. Chem. 1995, 60, 8142.
17. (a) Sivaprasad, S.; Sridhar, R.; Perumal, P. T. J. Heterocycl. Chem. 2006, 43, 389;
(b) Kumar, K. H.; Perumal, P. T. Chem. Lett. 2005, 34, 1346; (c) Kumar, H. K.;

5478
M. Damodiran et al. / Tetrahedron Letters 50 (2009) 5474–5478
Selvi, S.; Perumal, P. T. J. Chem. Res. 2004, 218; (d) Sridhar, R.; Perumal, P. T.
crushed ice and refrigerated overnight. The solution was neutralized with
sodium acetate and the crude compound was extracted with chloroform
(3 Â 50 mL) and washed with water (3 Â 25 mL). Organic layer was dried over
anhydrous sodium sulfate and concentrated under reduced pressure. The crude
product was purified through column chromatography using ethyl acetate:pet.
ether (1:1) as eluent. Colourless solid. Isolated Yield: 90%, mp: 264–266 °C. 1H
NMR (500 MHz, DMSO-d6) d: 6.75 (s, 1H), 7.50 (m, 2H), 7.58 (t, 1H, J = 7.7 Hz),
7.67 (m, 2H), 7.70 (t, 1H, J = 8.4 Hz), 8.00 (d, 1H, J = 7.7 Hz), 8.12 (d, 2H,
J = 9.2 Hz), 8.40 (s, 1H), 9.78 (br s, 2H, CHO), 11.84 (s, 1H, D2O exchangeable).
13C NMR (125 MHz, DMSO-d6) d: 50.3, 101.3 (O–C@C(CHO)2), 113.4, 117.2,
123.1, 124.3, 126.8, 128.8, 128.9, 129.6, 131.7, 131.8, 131.9, 134.5, 143.0, 144.8,
148.6, 162.1 (C@C–O), 186.7 (–CHO). IR mmax (KBr): 3429, 1621, 1579, 1449,
1222, 806 cmÀ1. Mass (ESI): 375 (M+1). Anal. Calcd for C21H14N2O5: C, 67.38, H,
3.77; N, 7.48. Found: C, 67.69; H, 3.83; N, 7.43. Spectral data for compound 2k:
Yellow solid. Isolated yield: 85%, mp: 170–172 °C. 1H NMR (500 MHz, CDCl3) d:
1.93 (s, 3H), 6.67 (s, 1H), 6.87 (dd, 1H, J = 1.5, 7.6 Hz), 7.22 (d, 1H, J = 8.5 Hz),
7.34–7.44 (m, 5H), 7.85 (d, 1H, J = 7.6 Hz), 7.92 (d, 1H, J = 9.2 Hz), 8.06 (dd, 1H,
J = 1.5, 8.5 Hz), 8.76 (s, 1H, CHO), 12.40 (s, 1H, D2O exchangeable). 13C NMR
(125 MHz, CDCl3) d: 10.5, 47.0 89.5 (O–C@C(CHO)2), 112.2, 116.8, 122.2, 125.6
(2), 128.1, 129.0, 129.4, 129.5, 131.0, 134.3, 146.6, 148.3, 159.2, 163.2 (C@C–O),
184.7 (–CHO). IR mmax (KBr): 3434, 1651, 1561, 1434, 1220, cmÀ1. Mass (ESI):
361 (M+1). Anal. Calcd for C21H16N2O4: C, 69.99, H, 4.48; N, 7.77. Found: C,
70.12; H, 3.93; N, 7.71. Spectral data for compound 2o: mp: 176–178 °C. 1H NMR
(500 MHz, CDCl3) d: 6.77 (s, 1H), 7.42–7.51 (m, 2H), 7.60–7.63 (m, 2H), 7.81 (m,
1H), 8.07 (d, 2H, J = 7.6 Hz), 8.28 (d, 1H, J = 8.4 Hz), 8.51 (s, 2H), 9.95 (s, 1H, D2O
exchangeable). 13C NMR (125 MHz, CDCl3) d: 48.5, 101.9 (C@C(CHO)2), 112.9,
122.9, 124.0, 125.2, 128.4, 130.2, 130.5, 130.6, 133.8, 134.9, 137.3, 149.4, 162.8,
Synth. Commun. 2003, 33, 607. 1483; (e) Selvi, S.; Perumal, P. T. Indian J. Chem.,
Sect. B 2002, 41B, 1887; (f) Selvi, S.; Perumal, P. T. Synth. Commun. 2001, 31,
2199; (g) Amaresh, R. R.; Perumal, P. T. Synth. Commun. 2000, 30, 2269; (h)
Selvi, S.; Perumal, P. T. Synth. Commun. 2000, 30, 3925; (i) Selvi, S.; Perumal, P.
T. Indian J. Chem., Sect. B 2000, 39B, 163; (j) Amaresh, R. R.; Perumal, P. T.
Tetrahedron 1999, 55, 8083; (k) Perumal, P. T.; Majo, V. J.; Anand, R. V. Indian J.
Chem., Sect. B 1999, 38, 763; (l) Amaresh, R. R.; Perumal, P. T. Tetrahedron 1998,
54, 14327; (m) Amaresh, R. R.; Perumal, P. T. Tetrahedron Lett. 1998, 39, 3837;
(n) Majo, V. J.; Perumal, P. T. J. Org. Chem. 1998, 63, 7136; (o) Selvi, S.; Perumal,
P. T. Tetrahedron Lett. 1997, 38, 6263; (p) Majo, V. J.; Perumal, P. T. Tetrahedron
Lett. 1997, 38, 6889; (q) Majo, V. J.; Perumal, P. T. Tetrahedron Lett. 1996, 37,
5015; (r) Balasundaram, B.; Venugopal, M.; Perumal, P. T. Tetrahedron Lett.
1996, 37, 5015; (s) Balasundaram, B.; Venugopal, M.; Perumal, P. T. Tetrahedron
Lett. 1993, 34, 4249.
18. (a) Savitha, G.; Perumal, P. T. Tetrahedron Lett. 2007, 48, 2943; (b) Damodiran,
M.; Kumar, R. S.; Sivakumar, P. M.; Doble, M.; Perumal, P. T. J. Chem. Sci. 2009,
121, 65; (c) Karthikeyan, K.; Perumal, P. T.; Etti, S.; Shanmugam, G. Tetrahedron
2007, 63, 10581; (d) Selvam, N. P.; Perumal, P. T. Tetrahedron 2008, 64, 2972;
(e) Selvam, N. P.; Saranya, S.; Perumal, P. T. Can. J. Chem. 2008, 86, 32; (f)
Shanthi, G.; Perumal, P. T. Tetrahedron Lett. 2007, 48, 6785; (g) Selvam, N. P.;
Shanthi, G.; Perumal, P. T. Can. J. Chem. 2007, 84, 989; (h) Thirumurugan, P.;
Muralidharan, D.; Perumal, P. T. Dyes Pigments 2009, 81, 245; (i) Thirumurugan,
P.; Perumal, P. T. Tetrahedron Lett. 2009, 50, 4145; (j) Damodiran, M.;
Muralidharan, D.; Perumal, P. T. Bioorg. Med. Chem. Lett. 2009, 19, 3611.
19. Selvam, N. P.; Perumal, P. T. Tetrahedron Lett. 2006, 47, 7481.
20. Representative procedure for the synthesis of [1-(3-nitrophenyl)-1,2-dihydro-3H-
naphtho[1,2-e][1,3]oxazine-3-ylidine]-malonaldehyde 2b (Table 1, entry 2): To
the solution containing acetamidonaphthol 1b (10 mmol) dissolved in DMF
(12 equiv), POCl3 (8 eqiuv) was added slowly dropwise (15 min) at 0 °C and the
reaction mixture was allowed to reach room temperature. Then the reaction
mixture was stirred at 90 °C for 3 h. After completion of the reaction, it was
allowed to cool to room temperature. The reaction mixture was poured into
(C@C–O), 190.1 (–CHO). IR m .
max (KBr): 3440, 1632, 1559, 1428, 1218, 812 cmÀ1
Mass (ESI): 325 (M+1). Anal. Calcd for C17H12N2O5: C, 62.96, H, 3.73; N, 8.68.
Found: C, 63.18, H, 3.78; N, 8.61.
21. NizamMohideen, M.; SubbiahPandi, A.; Selvam, N. P.; Perumal, P. T.;
Damodiran, M. Acta Crystallogr., Sect. E 2009, 65, o582.