A novel three-component one-pot reaction involving β-naphthol, aldehydes, and urea promoted by TMSCl/NaI

Article abstract of DOI:10.1002/jhet.328

(Chemical Equation Presented) Amidoalkyl naphthol derivatives have been synthesized in good yields in a one-pot condensation of b-naphthol, aromatic aldehydes and urea in presence of TMSCl/NaI at room temperature. Ring closure of amidoalkyl naphthol deriv

Full text of DOI:10.1002/jhet.328

272
A Novel Three-Component One-Pot Reaction Involving
b-Naphthol, Aldehydes, and Urea Promoted by TMSCl/NaI
Gowravaram Sabitha,a* K. Arundhathi,a K. Sudhakar,a B. S. Sastry,b
and J. S. Yadava
Vol 47
aOrganic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
bUniversity College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, India
*E-mail: gowravaramsr@yahoo.com
Received June 26, 2009
DOI 10.1002/jhet.328
Published online 20 January 2010 in Wiley InterScience (www.interscience.wiley.com).
Amidoalkyl naphthol derivatives have been synthesized in good yields in a one-pot condensation of
b-naphthol, aromatic aldehydes and urea in presence of TMSCl/NaI at room temperature. Ring closure
of amidoalkyl naphthol derivatives occurred at 140ꢀC to afford 1,2-dihydro-1-arylnaphtho[1,2-e]
[1,3]oxazin-3-one derivatives.
J. Heterocyclic Chem., 47, 272 (2010).
INTRODUCTION
RESULTS AND DISCUSSION
Multicomponent reactions have emerged as powerful
strategies with the emphasis on the search for atom-effi-
cient transformations of easily available starting materi-
als into complex organic molecules, which provide max-
imum diversity are encouraging on economy and envi-
ronmental grounds [1]. One such example is the reaction
of b-naphthol and aldehydes with urea to produce ami-
doalkyl naphthols or oxazinone derivatives. Benzoxazin-
4-one derivatives are an important class of heterocyclic
compounds [2–5], which exibit many industrial,
research, and clinical applications. Naphthalene con-
densed oxazinone derivatives are known to possess
interesting pharmacological and reported as antibacterial
agents [6]. These compounds have also been used in the
preparation of chiral amino phosphine ligands for asym-
metric catalysis [7]. Even though a large number of
methods [8–15] were reported for the preparation of in-
termediate compounds (amidoalkyl naphthols), ring clo-
sure reactions to give naphthalene condensed oxazinone
derivatives have not been thoroughly investigated [16–
19]. This has stimulated significant interest and there is
always considerable demand in exploring more milder,
convenient, practical, and efficient reagents for their
synthesis using multicomponent reactions. Therefore, the
development of simple, convenient, and practical proce-
dures for the synthesis of naphtho[1,2-e][1,3]oxazin-3-
one derivatives continue to be a challenging endeavor in
synthetic organic chemistry.
TMSCl/NaI combination has been explored in various
organic transformations [19]. In continuation of our
efforts to explore the synthetic utility of TMSCl/NaI
combination [20], herein we report a three-component
approach for the one-pot synthesis of a series of ami-
doalkyl naphthols and naphthoxazinones under different
reaction conditions using TMSCl/NaI (Scheme 1).
Initially, we examined the reaction of naphthol (1),
benzaldehyde (2), and urea (3) in the presence of TMSCl/
NaI in CH3CN at room temperature and found to give the
corresponding intermediate amidoalkyl naphthol deriva-
tive 4a in 81% yield. The structure of the product was
confirmed by spectral data and compared with the authen-
tic sample. Similarly, other aromatic aldehydes were also
reacted to give the intermediate compounds in good
yields at room temperature (Scheme 2) and the results are
presented in Table 1. Under present conditions, formation
of side products, such as, dibenzoxanthenes was not
observed. When an intermediate amidoalkyl naphthol de-
rivative 4a was heated in DMF at 140ꢀC for 1.2 h cycliza-
tion occurred to produce the naphthoxazinone 5a. Encour-
aged by this result, the reaction of b-naphthol (1), benzal-
dehyde (2), and urea (3) in the presence of TMSCl/NaI in
CH3CN/DMF (4:1) was directly heated at 140ꢀC and
found to give the cyclized product, naphthoxazinone 5a
exclusively within 1 h, without isolating the intermediate
4a. To find out the scope and generality of this reaction,
we turned our attention to various substituted aldehydes.
C
V
2010 HeteroCorporation

March 2010
A Novel Three-Component One-Pot Reaction Involving b-Naphthol, Aldehydes,
and Urea Promoted by TMSCl/NaI
273
Scheme 1
Table 1
TMSCI/NaI catalyzed synthesis of amidoalkyl naphthols (4).a,b
Entry
4a
Aldehyde
Time (h)
1.5
Yield (%)
mp (ꢀC)
212
81
79
4b
1.8
208
4c
4d
4e
1.2
3
78
78
81
193
198
179
2.3
The aromatic aldehydes containing both electron-donat-
ing and electron-withdrawing groups afforded the desired
products. All the reactions were clean at 140ꢀC and
the corresponding cyclized products 5b–m were obtained
in good yields without isolating intermediate compounds
4. The results are summarized in Table 2. The products
were characterized by spectral data and known com-
pounds were compared with the authentic samples data.
In summary, we have demonstrated an efficient proto-
col for the synthesis of amidoalkyl naphthols and naph-
thoxazinone derivatives using TMSCl/NaI as promoter.
The notable features of this method are mild reaction
conditions, greater selectivity, simplicity in operation,
which make it an attractive and very useful process for
the synthesis of amidoalkyl naphthol and naphthoxazi-
none derivatives of biological importance.
a All products were confirmed by their spectral data and compared
with authentic samples.
b Isolated yields after purification.
equiv. of urea in acetonitrile (10 mL) was added 1.5 equiv. of
TMSCl and 1.5 equiv. of NaI at 0ꢀC and stirred at room tem-
perature (see Table 1). After completion, followed by TLC,
acetonitrile was removed and ethyl acetate was added to the
residue. Ethyl acetate was washed with water, sodium thiosul-
fate, and brine solution, dried, and concentrated. The crude
residue was purified by column chromatography (EtOAc/hex-
ane, 1:3) to afford the pure product 4.
A mixture of intermediate amidoalkyl naphthol derivative 4
in DMF was heated at 140ꢀC for 1–3 h. After completion of
cyclization reaction, followed by TLC, water was added and
extracted with ether. The organic layer was washed with water
and brine solution, dried, and concentrated. The crude residue
was purified by column chromatography (EtOAc/hexane, 1:3)
to afford naphthoxazinone product 5.
EXPERIMENTAL
General procedure for the one-pot synthesis of naphthox-
azinones 5. To a mixture of 1 equiv. of b-naphthol, 1 equiv.
of aromatic aldehyde and 1.5 equiv. of urea in acetonitrile/di-
methyl formamide (6 mL:1.5 mL; 4:1) was added 1.5 equiv.
of TMSCl and 1.5 equiv. of NaI at 0ꢀC and stirred at 140ꢀC
(see Table 2). After completion, followed by TLC, solvent
mixture was removed by rotary evaporation and ethyl acetate
was added to the residue. Ethyl acetate was washed with
water, sodium thiosulfate, and brine solution, dried, and con-
centrated. The crude residue was purified by column chroma-
tography (EtOAc/hexane, 1:3) to afford the pure product 5.
Spectral data of amidoalkyl naphthol derivatives 4.
Compound 4a. mp 212ꢀC; 1H NMR (300 MHz, DMSO): 5.55
(s, 2H), 7.22.7.51 (m, 9H), 7.63–7.81 (m, 2H), 7.94–8.20 (d, J ¼
7.8 Hz, 2H), 9.80 (s, 1H). IR (KBr): 3450, 3210, 1640, 1575,
1510, 1425, 1360, 1242, 816 cmꢁ1. ESI MS: m/z 292 (Mþ).
Compound 4b. mp 208ꢀC; 1H NMR (200 MHz, DMSO):
5.61 (s, 2H), 7.05–7.42 (m, 8H), 7.65–7.83 (d, J ¼ 11.2 Hz,
1H), 8.23 (d, J ¼ 8.2 Hz, 1H), 9.95 (s, 1H). IR (KBr): 3420,
3320, 1651, 1570, 1520, 1420, 1362, 1242, 815 cmꢁ1. ESI
MS: m/z 326 (Mþ).
Melting points were recorded on Buchi R-535 apparatus and
are uncorrected. IR spectra were recorded on a PerkinElmer
FTIR 240-c spectrophotometer using KBr optics. 1H NMR
spectra were recorded onVarian-unity 300 spectrometer in
CDCl3 using TMS as internal standard. Mass spectra were
recorded on a Finnigan MAT 1020 mass spectrometer operat-
ing at 70 eV.
General procedure for the synthesis of amidoalkyl naph-
thol derivatives 4 and naphthoxazinones 5. To a mixture of
1 equiv. of b-naphthol, 1 equiv. of aromatic aldehyde and 1.5
Scheme 2
Compound 4c. mp 193ꢀC; 1H NMR (300 MHz, DMSO):
3.75 (s, 3H), 5.53 (s, 2H), 7.52–7.81 (m, 8H), 7.95–8.12 (m,
2H), 8.24 (d, J ¼ 8.2 Hz, 2H), 9.65 (s, 1H). IR (KBr): 3410,
3320, 1650, 1578, 1523, 1425, 1362, 1240, 780 cmꢁ1. ESI
MS: m/z 322 (Mþ).
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G. Sabitha, K. Arundhathi, K. Sudhakar, B. S. Sastry, and J. S. Yadav
Vol 47
Compound 4d. mp 198ꢀC; 1H NMR (300 MHz DMSO):
5.65 (s, 2H), 7.52–7.65 (m, 8H), 7.72–7.96 (m, 2H), 8.34 (d, J
¼ 8.3 Hz, 2H), 9.73 (s, 1H). IR (KBr): 3445, 3322, 1646,
1575, 1530, 1415, 1360, 1242, 816, 780 cmꢁ1. ESI MS: m/z
308 (Mþ).
Table 2
TMSCI/NaI catalyzed synthesis of naphtho[1,2-e][ ]
benzoxazinones (5).a,b
Compound 4e. mp 179ꢀC; 1H NMR (200 MHz, DMSO):
2.13 (s, 3H), 5.56 (s, 2H), 6.92–7.85 (m, 8H), 7.93–8.13 (m,
2H), 8.34 (d, J ¼ 8.3 Hz, 2H), 9.63 (s, 1H). IR (KBr): 3420,
3326, 1652, 1572, 1475, 1365, 1241, 860, 781 cmꢁ1. ESI MS:
m/z (%) 306 (Mþþ1).
Entry
Aldehyde
Time (h) Yield (%) mp (ꢀC)
5a
2
78
219
Spectral data of naphthoxazines 5.
Compound 5a. mp 219ꢀC; 1H NMR (300 MHz, DMSO):
6.12 (d, J ¼ 2.26 Hz, 1H), 7.24–8.12 (m, 3H), 8.88 (brs, 1H).
IR (KBr): 3296, 1721, 1517, 720 cmꢁ1. ESI MS: m/z 275 (Mþ).
Compound 5b. mp 208ꢀC; 1H NMR (300 MHz, DMSO):
6.21 (s, 1H), 7.26–8.10 (m, 10H), 8.92 (brs, 1H). IR (KBr):
3229, 3142, 1734, 1517, 747 cmꢁ1. ESI MS: m/z 310
(Mþþ1).
5b
5c
5d
5e
5f
2.6
1.5
1.9
2.4
1.6
2.4
86
86
79
89
78
86
208
203
221
182
187
166
Compound 5c. mp 203ꢀC; 1H NMR (200 MHz, CDCl3):
6.23 (s, 1H), 7.31–8.02 (m, 10H), 8.94 (brs, 1H). IR (KBr):
3126, 1751, 1509, 736 cmꢁ1. ESI MS: m/z (%) 293 (Mþ).
Compound 5d. mp 221ꢀC; 1H NMR (200 MHz, DMSO):
6.21 (s, 1H), 7.20–8.13 (m, 10H), 8.90 (brs, 1H). IR (KBr):
3229, 3146, 1730, 1515, 723 cmꢁ1. ESI MS: m/z 377
(MþþNa).
Compound 5e. mp 182ꢀC; 1H NMR (300 MHz, DMSO):
5.6 (s, 1H), 7.32–8.20 (m, 10H), 8.55 (brs, 1H), 11.10 (s, 1H).
IR (KBr): 3673, 3215, 1701, 1551, 746 cmꢁ1. ESI MS: m/z
291 (Mþ).
Compound 5f. mp 187ꢀC; 1H NMR (200 MHz, DMSO):
3.76 (s, 3H), 6.24 (s, 1H), 7.20–8.01 (m, 10H), 8.65 (brs, 1H).
IR (KBr): 3149, 2942, 1733, 1607, 1510, 842, 723 cmꢁ1. ESI
MS: m/z 305(Mþ).
5g
Compound 5g. mp 166ꢀC; 1H NMR (300 MHz, DMSO):
2.03 (s, 3H), 6.26 (s, 1H), 7.26–8.05 (m, 10H), 8.86 (brs, 1H).
IR (KBr): 3148, 2921, 1735, 1512, 723 cmꢁ1. ESI MS: m/z
289 (Mþ).
5h
5i
3
81
80
172
178
Compound 5h. mp 172ꢀC; 1H NMR (300 MHz DMSO):
1.25 (s, 6H), 2.56 (m, 1H), 6.01 (d, J ¼ 2.86 Hz, 1H), 7.24–
8.08 (m, 10H), 8.82 (brs, 1H). IR (KBr): 3281, 2924, 1729,
1513, 830 cmꢁ1. ESI MS: m/z 317 (Mþ).
2.5
Compound 5i. mp 178ꢀC; 1H NMR (200 MHz, DMSO):
1.24 (s, 6H), 1.31 (s, 3H), 6.30 (s, 1H), 7.40–8.19 (m, 10H),
8.92 (brs, 1H). IR (KBr): 3203, 2959, 1727, 1515, 828, 740
cmꢁ1. ESI MS: m/z (%) 332 (Mþþ1).
5j
4
62
68
199
222
Compound 5j. mp 199ꢀC; 1H NMR (300 MHz, DMSO):
6.13 (s, 1H), 7.21–8.06 (m, 10H), 8.92 (brs, 1H). IR (KBr):
3220, 3142, 1729, 1513, 820, 748 cmꢁ1. ESI MS: m/z 309
(Mþ).
5k
3.2
Compound 5k. mp 222ꢀC; 1H NMR (200 MHz, DMSO):
6.20 (s, 1H), 7.18–8.06 (m, 10H), 8.91 (brs, 1H). IR (KBr):
3252, 3140, 1730, 1512, 823, 758 cmꢁ1. ESI MS: m/z 355
(Mþþ1).
5l
4.9
66
71
172
189
Compound 5l. mp 172ꢀC; 1H NMR (200 MHz, CDCl3):
3.78 (s, 3H), 6.12 (s, 1H), 7.03–8.06 (m, 10H), 8.93 (s, 1H).
IR (KBr): 3149, 1733, 1510, 814, 743 cmꢁ1. ESI MS: m/z 306
(Mþþ1).
5m
5
Compound 5m. mp 191ꢀC; 1H NMR (200 MHz, DMSO):
6.01 (d, J ¼ 3.38 Hz, 1H), 6.98–8.01 (m, 10H), 8.56 (brs, 1H).
IR (KBr): 3423, 3299, 1730, 1515, 812, 743 cmꢁ1. ESI MS:
m/z 292 (Mþþ1).
a All products were characterized by spectral data and compared with
the authentic samples.
b Isolated pure products.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2010
A Novel Three-Component One-Pot Reaction Involving b-Naphthol, Aldehydes,
and Urea Promoted by TMSCl/NaI
275
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet