Simple and one-pot synthesis of tri and tetracyclic frameworks containing [1,8]naphthyridin-2-one moiety from the Baylis-Hillman adducts

Article abstract of DOI:10.1016/j.tet.2009.12.033

A facile synthesis of tri and tetracyclic frameworks containing [1,8]naphthyridin-2-one skeleton from the Baylis-Hillman alcohols via the Johnson-Claisen rearrangement, followed by the treatment with Fe/AcOH in simple one-pot multi-step process is describ

Full text of DOI:10.1016/j.tet.2009.12.033

Tetrahedron 66 (2010) 1215–1219
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Tetrahedron
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Simple and one-pot synthesis of tri and tetracyclic frameworks containing
[1,8]naphthyridin-2-one moiety from the Baylis–Hillman adducts
*
Deevi Basavaiah , Kanumuri Ramesh Reddy
School of Chemistry, University of Hyderabad, Central University (PO), Gachibowli, Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile synthesis of tri and tetracyclic frameworks containing [1,8]naphthyridin-2-one skeleton from the
Baylis–Hillman alcohols via the Johnson–Claisen rearrangement, followed by the treatment with Fe/
AcOH in simple one-pot multi-step process is described.
Received 8 September 2009
Received in revised form 9 December 2009
Accepted 10 December 2009
Available online 16 December 2009
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Baylis-Hillman reaction
Johnson–Claisen rearrangement
Reduction
Cyclization
[1,8]naphthyridin-2-ones
Fe/AcOH
DABCO
1. Introduction
from the Baylis–Hillman (B–H) adducts, derived from 2-nitro-
benzaldehydes/1-nitro-2-naphthaldehyde and acrylonitrile.
The Baylis–Hillman reaction has been and continues to attract
the attention of synthetic chemists as it provides a variety of
2. Results and discussion
densely functionalized molecules via the coupling of a-position of
activated alkenes with electrophiles under the influence of a cata-
lyst/catalytic system in operationally simple one-pot procedure.1,2
Applications of these multifunctional molecules, which are nor-
mally referred to as the Baylis–Hillman adducts, have been well
documented in various organic transformation methodologies.1,2
The [1,8]naphthyridine derivatives3–5 represent an important
class of molecules, which are found to possess interesting bio-
logical properties, such as antiinflammatory,4a,b analgesic,4a
antiaggressive,4b anticancer,4c antibacterial,4d antitumor,4e anti-
hypertensive,4f antiallergitic,4g antimalarial,4h and also they are
found to be potential diuretic agents.4i Therefore, there has been
increasing interest in developing facile methodologies for syn-
thesis of [1,8]naphthyridine framework of medicinal relevance.5–7
In continuation of our interest in the development of Baylis–
Hillman adducts8 as a valuable source for various interesting
methodologies and also for one-pot multi-step synthesis we,
herein, report a facile one-pot synthesis of tri and tetracyclic
systems containing [1,8]naphthyridin-2-one framework starting
Most of the known methodologies for synthesis of [1,8]naph-
thyridine framework employ either 2-aminopyridine or 2-halo-
pyridine derivatives5 as the key starting materials. In the year 1963
Junek reported an interesting synthesis of [1,8]naphthyridine
framework via the condensation of 2-nitrobenzaldehydes with
appropriate malononitrile derivatives followed by reduction of the
nitro group and subsequent cyclization providing the desired
[1,8]naphthyridine framework.6 Batra and co-workers also used
similar type of cyclization for the synthesis of fused polycyclic
quinolines from the acetates of B-H alcohols, derived from
2-nitrobenzaldehydes.9 Our research group10 has, a few years ago,
described the Johnson–Claisen rearrangement of Baylis–Hillman
alcohols obtained from various aldehydes and acrylonitrile
providing 4-cyanoalk-4-enoates with exclusive (Z)-selectivity in
good yields. Recently we have also developed a convenient meth-
odology for facile transformation of the Baylis–Hillman adducts
derived from 2-nitrobenzaldehydes and cyclohex-2-enones into
tetrahydroacridine derivatives.8e Since the benzo[b][1,8]-naph-
thyridine moiety (A) is nothing but aza version of acridine skeleton
(B) (Fig. 1) we became interested in developing a simple synthetic
protocol for obtaining such derivatives from the Baylis–Hillman
adducts.
* Corresponding author. Tel.: þ91 040 23134812; fax: þ91 40 23012460.
E-mail address: dbsc@uohyd.ernet.in (D. Basavaiah).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.12.033

1216
D. Basavaiah, K.R. Reddy / Tetrahedron 66 (2010) 1215–1219
Table 1
A
B
Synthesis of benzo[b][1,8]naphthyridin-2-one derivatives from the Baylis–Hillman
alcoholsa
N
N
N
1. R3CH2C(OEt)3
145 °C, 70 h
EtCOOH (Cat.)
OH
Benzo[b][1,8]naphthyridine
Acridine
R1
R2
R3
O
R1
R2
CN
Figure 1. Benzo[b][1,8]naphthyridine (A) and acridine (B) frameworks.
N
2-11
N
H
NO2
2. Fe/AcOH
110 °C,1 h
1a-e
From our experience on the synthesis of heterocyclic com-
pounds using the Baylis–Hillman adducts,8a–j it occurred to us that
the products (X) obtained via the Johnson–Claisen rearrangement
of Baylis–Hillman alcohols (1), derived from 2-nitrobenzaldehydes
and acrylonitrile, could serve as appropriate synthons for the syn-
thesis of benzo[b][1,8]naphthyridin-2-one framework through re-
ductive cyclization protocol. We also felt that all these steps, in
principle, can be performed in one-pot operation as described in
retro-synthetic strategy (Scheme 1).
B–H Alcohol
R1
R2
R3
Product
Yieldb,c(%)
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
H
H
Br
Br
Cl
H
H
H
H
H
H
OMe
OMe
OEt
OEt
Me
H
Me
H
Me
H
Me
H
2
3
4
5
6
7
8
9
69
55
56
45
63
58
60
48
56
49
Cl
OMe
OMe
OMe
OMe
Me
H
10
11
a
C-N bond
cleavage
All reactions were carried out on a 1 mmol scale of B–H alcohols with triethyl
orthopropionate (1.25 mL) or triethyl orthoacetate (2.0 mL) at 145 ꢀC in the pres-
ence of a catalytic amount of propanoic acid11 followed by reductive cyclization.
R'
R'
O
CN COOEt
N
N
H
R
R
R
NO2
b
All the compounds were fully characterized (see Experimental section).
Yields were based on B–H alcohols.
X
c
Johnson-Claisen
Rearrangement
Table 2
Synthesis of tetracyclic compounds containing [1,8]naphthyridin-2-one frameworka
OH
CHO
CN Baylis-Hillman
Reaction
OH
1. R3CH2C(OEt)3
145 °C,70 h
EtCOOH (Cat.)
R3
O
+
CN
CN
NO2
NO2
R
N
N
H
NO2
1
2. Fe/AcOH
110 °C, 1 h
12, 13
Scheme 1. Retro-synthetic strategy.
1f
B–H Alcohol
R3
Me
Product12,13
12d
13d
Yieldb,c (%)
Accordingly, we have, first, selected 3-(2-nitrophenyl)-3-hy-
droxy-2-methylenepropanenitrile (1a), Baylis–Hillman (B–H) al-
cohol, obtained from 2-nitrobenzaldehyde and acrylonitrile
under the catalytic influence of DABCO, as a substrate for the
multi-step one-pot reaction sequence to obtain the desired ben-
zo[b][1,8]naphthyridin-2-one derivative (2). In this direction the
best result was obtained when 3-(2-nitrophenyl)-3-hydroxy-2-
methylenepropanenitrile (1a) was treated with triethyl ortho-
propionate in the presence of a catalytic amount of propanoic
acid11 at 145 ꢀC for 70 h followed by the treatment of the
resulting product (obtained after removal of excess triethyl ortho-
propionate under reduced pressure) with Fe/AcOH at 110 ꢀC for
1 h, thus providing the expected 2,4-diaza-6-methyltricyclo-
[8.4.0.03,8]tetradeca-1(10),2,8,11,13-pentaen-5-one (2) in 69% iso-
lated yield (Table 1).
1f
1f
59
51
H
a
All reactions were carried out on a 1 mmol scale of B–H alcohol with triethyl
orthopropionate (1.25 mL) or triethyl orthoacetate (2.0 mL) at 145 ꢀC in the pres-
ence of a catalytic amount of propanoic acid followed by reductive cyclization.
b
Compounds 12 and 13 were fully characterized (see Experimental section).
c
Yields were based on B–H alcohol.
d
Compounds 12 and 13 were further confirmed by single crystal data.12,13
12
Encouraged by this result, we have successfully transformed
the various Baylis–Hillman adducts (Table 1, 1a–e) into ben-
zo[b][1,8]naphthyridin-2-ones (3–11) in 45–63% isolated yields
(Table 1).
13
Figure 2. ORTEP diagrams of compounds 12 and 13 (Hydrogen atoms were omitted for
clarity).12,13
With a view to understand the generality and also to obtain
tetracyclic system having [1,8]naphthyridin-2-one framework we
rearrangement of the B–H alcohol to provide trisubstitutued al-
kene (X). The second step proceeds through the reduction of
nitro group with Fe/AcOH to generate the amine, in situ, which
on subsequent cyclization might provide the desired [1,8]naph-
thyridin-2-one framework (Scheme 2).
have
prepared
3-(1-nitronaphth-2-yl)-3-hydroxy-2-methyl-
enepropanenitrile (1f) (from 1-nitro-2-naphthaldehyde and ac-
rylonitrile) and subjected to Johnson–Claisen rearrangement
with triethyl orthopropionate and triethyl orthoacetate and
subsequent reductive cyclization using Fe/AcOH. The resulting
products
3,5-diaza-7-methyltetracyclo[12.4.0.02,11.04,9]ocatdeca-
3. Conclusion
1(14),2(11),3,9,12,15,17-heptaen-6-one (12) and 3,5-diazatetracyclo-
[12.4.0.02,11.04,9]ocatdeca-1(14),2(11),3,9,12,15,17-heptaene-6-one
(13) were obtained in 59% and 51% isolated yields, respectively
(Table 2). In fact structures of these molecules were further
confirmed by single crystal X-ray data (Fig. 2).12,13 A plausible
mechanism for this one-pot interesting transformation is pre-
sented in Scheme 2. The first step involves Johnson–Claisen
In conclusion, we have successfully developed a simple, facile
and one-pot procedure for the synthesis of tri and tetracyclic het-
erocyclic systems containing [1,8]naphthyridin-2-one framework
from the Baylis–Hillman alcohols, thus demonstrating the impor-
tance of Baylis–Hillman alcohols as valuable synthons in organic
chemistry.

D. Basavaiah, K.R. Reddy / Tetrahedron 66 (2010) 1215–1219
1217
129.65, 135.40, 146.20, 150.64, 174.60; LCMS (m/z): 213 (MþH)þ;
Anal. Calcd for C13H12N2O: C, 73.56; H, 5.70; N, 13.20. Found: C,
73.71; H, 5.69; N, 13.28.
Similarly, compounds 4, 6, 8, 10, 12 were prepared following the
above mentioned procedure. The compounds 3, 5, 7, 9, 11, 13 were
synthesized via Johnson–Claisen rearrangement of corresponding
Baylis–Hillman alcohols 1a, 1b, 1c, 1d, 1e, 1f, respectively, with
triethyl orthoacetate (2.0 mL), in the presence of catalytic amount
of propanoic acid, followed by reductive cyclization using Fe/AcOH.
OH
R3
CN
Johnson-Claisen
Rearrangement
CN COOEt
NO2
X
R
R
NO2
Fe/AcOH
Reduction
R3
OEt
R3
OEt
Cyclization
C
N
N
N
R
NH2
R
O
H
O
4.2.2. 2,4-Diazatricyclo[8.4.0.03,8]tetradeca-1(10),2,8,11,13-pentaen-
-EtOH
-EtOH
Cyclization
5-one (3). Yield: 55%; Rf (40% EtOAc in hexanes) 0.33; reaction
time: 71 h (70 hþ1 h); mp: 210–211 ꢀC (dec); IR (KBr):
n
3350–3100
2.76
R3
O
R3
(multiple bands),1695,1682,1626 cmꢁ1; 1H NMR (400 MHz):
d
N
H
N
N
N
H
O
(t, 2H, J¼7.2 Hz), 3.14 (t, 2H, J¼7.2 Hz), 7.40–7.47 (m, 1H), 7.61–7.68
R
R
(m, 1H), 7.72 (d, 1H, J¼8.0 Hz), 7.86 (d, 1H, J¼8.4 Hz), 7.92 (s, 1H),
8.28 (s, 1H, D2O exchangeable); 13C NMR (100 MHz):
d 24.70, 30.80,
Scheme 2. A Plausible mechanism for synthesis of tri and tetracyclic system con-
taining [1,8]naphthyridin-2-one framework.
119.57, 125.22, 125.97, 127.19, 127.53, 129.73, 135.26, 146.21, 150.54,
171.83; LCMS (m/z): 199 (MþH)þ; Anal. Calcd for C12H10N2O: C,
72.71; H, 5.08; N, 14.13. Found: C, 72.59; H, 5.12; N, 14.23.
4. Experimental section
4.1. General remarks
4.2.3. 12-Bromo-2,4-diaza-6-methyltricyclo[8.4.0.03,8]tetradeca-1(10),
2,8,11,13-pentaen-5-one (4). Yield: 56%; Rf (40% EtOAc in hexanes)
0.59; reaction time: 71 h (70 hþ1 h); mp: 215–217 ꢀC; IR (KBr):
n
Melting points were recorded on a Superfit (India) capillary
melting point apparatus and were uncorrected. IR spectra were
recorded on a JASCO-FTIR model 5300 spectrometer using solid
samples as KBr plates. 1H NMR (400 MHz) and 13C NMR (100 MHz)
spectra for all compounds were recorded in deuterochloroform
(CDCl3) or in deuterochloroform (CDCl3) containing deutero-
dimethyl sulfoxide (DMSO-d6) on a Bruker-AVANCE-400 spec-
3350–3160 (multiple bands), 1691, 1624 cmꢁ1 1H NMR (400 MHz):
;
d
1.35 (d, 3H, J¼6.8 Hz), 2.72–2.96 (m, 2H), 3.18 (dd,1H, J¼5.6 Hz and
15.6 Hz), 7.69 (d, 1H, J¼9.2 Hz), 7.78 (d, 1H, J¼9.2 Hz), 7.81 (s, 1H),
7.86 (s, 1H), 8.61 (s, 1H, D2O exchangeable); 13C NMR (100 MHz) (90%
CDCl3þ10% DMSO-d6):
d 15.28, 32.46, 34.88, 118.17, 120.66, 126.81,
128.94, 128.99, 132.62, 134.12, 144.58, 150.90, 174.46; LCMS (m/z):
291(MþH)þ, 293(Mþ2þH)þ; Anal. Calcd for C13H11BrN2O: C, 53.63;
H, 3.81; N, 9.62, Found: C, 53.67; H, 3.71; N, 9.58.
trometer using tetramethylsilane (TMS,
d
¼0) as an internal
standard at room temperature. Elemental analyses were recorded
on a Thermo–Finnigan Flash EA 1112 analyzer. Mass spectra were
recorded on Shimadzu-LCMS-2010 A mass spectrometer. The X-
ray diffraction measurements were carried out at 100 K on
a Bruker SMART APEX CCD area detector system equipped with
a graphite monochromator and a Mo-K
¼0.71073 Å).
4.2.4. 12-Bromo-2,4-diazatricyclo[8.4.0.03,8]tetradeca-1(10),2,8,11,13-
pentaen-5-one (5). Yield: 45%; Rf (40% EtOAc in hexanes) 0.38; re-
action time: 71 h (70 h þ1 h); mp: 248–249 ꢀC (dec); IR (KBr):
n
3250–3000 (multiple bands), 1685, 1626 cmꢁ1; 1H NMR (400 MHz):
a fine-focus sealed tube
d
2.77 (t, 2H, J¼7.6 Hz), 3.14 (t, 2H, J¼7.6 Hz), 7.69 (dd, 1H, J¼2.0 Hz
and 8.8 Hz), 7.78 (d,1H, J¼8.8 Hz), 7.82 (s,1H), 7.86 (d,1H, J¼2.0 Hz),
8.65 (br s, 1H, D2O exchangeable); 13C NMR (100 MHz):
24.69,
(l
d
4.2. Representative procedure
30.61, 118.66, 120.66, 127.10, 129.18, 129.23, 133.07, 134.22, 144.81,
150.82, 171.63; LCMS (m/z): 275(MꢁH)þ, 277 (MꢁHþ2)þ; Anal.
Calcd for C12H9BrN2O: C, 52.01; H, 3.27; N, 10.11. Found: C, 52.20; H,
3.29; N, 10.04.
4.2.1. Synthesis of 2,4-diaza-6-methyltricylo[8.4.0.03,8]tetradeca-1(10),
2,8,11,13-pentaen-5-one (2). To a stirred solution of 3-(2-nitro-
phenyl)-3-hydroxy-2-methylenepropanenitrile 1a (1 mmol, 0.204 g)
in triethyl orthopropionate (1.25 mL) was added catalytic amount of
propanoic acid (four drops), and the reaction mixture was heated at
145 ꢀC for 70 h. The reaction mixture was then allowed to come to
room temperature. Excess triethyl orthopropionate was removed
under reduced pressure. The residue, thus obtained, was diluted
with AcOH (5 mL) and electrolytic Fe powder (6 mmol, 0.336 g), at
room temperature, was added. Then the reaction mixture was
heated at 110 ꢀC for 1 h and was cooled to room temperature. Acetic
acid was removed under reduced pressure and diluted with EtOAc
(15 mL). The resulting mixture was filtered to remove any iron im-
purities. Iron residue was washed twice with EtOAc (15 mL). Filtrate
and washings were combined and dried over anhydrous Na2SO4.
Solvent was evaporated and the residue thus obtained was purified
by column chromatography (40% EtOAc in hexanes) to provide the
desired product as colorless solid in 69% (0.147 g) isolated yield. Rf
4.2.5. 12-Chloro-2,4-diaza-6-methyltricyclo[8.4.0.03,8]tetradeca-
1(10),2,8,11,13-pentaen-5-one (6). Yield: 63%; Rf (40% EtOAc in
hexanes) 0.57; reaction time: 71 h (70 hþ1 h); mp: 210–212 ꢀC
(dec); IR (KBr):
n 3350–3150 (multiple bands), 1709, 1685,
1626 cmꢁ1; 1H NMR (400 MHz):
d
1.35 (d, 3H, J¼6.8 Hz), 2.72–2.95
(m, 2H), 3.18 (dd, 1H, J¼5.2 Hz and 15.6 Hz), 7.57 (dd, 1H, J¼2.4 Hz
and 8.8 Hz), 7.69 (d,1H, J¼2.4 Hz), 7.82 (s,1H), 7.89 (d,1H, J¼8.8 Hz),
8.91 (br s, 1H, D2O exchangeable); 13C NMR (100 MHz):
d 15.51,
32.72, 35.17, 120.78, 125.88, 126.53, 129.01, 130.45, 130.63, 134.45,
144.59, 150.81, 174.37; LCMS (m/z): 247 (MþH)þ, 249 (MþHþ2)þ;
Anal. Calcd for C13H11ClN2O: C, 63.29; H, 4.49; N, 11.36. Found: C,
63.13; H, 4.44; N, 11.41.
4.2.6. 12-Chloro-2,4-diazatricyclo[8.4.0.03,8]tetradeca-1(10),2,8,11,13-
pentaen-5-one (7). Yield: 58%; Rf (40% EtOAc in hexanes) 0.39;
(40% EtOAc in hexanes) 0.58; mp: 212–214 ꢀC, IR (KBr):
n
3350–3150
1.35
reaction time: 71 h (70 hþ1 h); mp: 246–248 ꢀC; IR (KBr):
n 3300–
(multiple bands), 1693, 1678, 1626 cmꢁ1; 1H NMR (400 MHz):
d
3000 (multiple bands), 1700, 1687, 1626 cmꢁ1; 1H NMR (400 MHz):
(d, 3H, J¼6.8 Hz), 2.71–2.97 (m, 2H), 3.18 (dd, 1H, J¼5.2 Hz and
15.6 Hz), 7.38–7.48 (m, 1H), 7.60–7.68 (m, 1H), 7.71 (d, 1H, J¼8.0 Hz),
7.88–7.95 (m, 2H), 8.55 (s, 1H, D2O exchangeable); 13C NMR
d
2.77 (t, 2H, J¼7.2 Hz), 3.14 (t, 2H, J¼7.2 Hz), 7.57 (d, 1H, J¼8.8 Hz),
7.68 (s, 1H), 7.83 (s, 1H), 7.92 (d, 1H, J¼8.8 Hz), 9.12 (s, 1H, D2O
exchangeable); 13C NMR (100 MHz):
24.72, 30.64, 120.68, 125.94,
126.59, 129.09, 130.53, 130.77, 134.31, 144.63, 150.70, 171.52; LCMS
d
(100 MHz): d 15.53, 32.73, 35.26,119.63,125.08,125.91,127.11,127.49,

1218
D. Basavaiah, K.R. Reddy / Tetrahedron 66 (2010) 1215–1219
(m/z): 233 (MþH)þ, 235 (MþHþ2)þ; Anal. Calcd for C12H9ClN2O: C,
dimensions, 0.34ꢂ0.22ꢂ0.06 mm3; crystal system, monoclinic;
lattice type, primitive; lattice parameters, a¼15.2721(9) Å,
61.95; H, 3.90; N, 12.04. Found: C, 61.78; H, 3.95; N, 12.00.
b¼12.3272(8) Å, c¼15.1619(9) Å,
a
¼90.00;
b
¼113.1960(10);
4.2.7. 2,4-Diaza-12,13-dimethoxy-6-methyltricyclo[8.4.0.03,8]te-
tradeca-1(10),2,8,11,13-pentaen-5-one (8). Yield: 60%; Rf (40% EtOAc
in hexanes) 0.31; reaction time: 71 h (70 hþ1 h); mp: 236–238 ꢀC
g
¼90.00; V¼2623.7(3) Å3; space group, p 21/c, Z¼8; Dcalcd¼1.328 g/
cm3; F000¼1104;
l
(Mo-K
a
)¼0.71073 Å;
R
(Iꢃ2s1)¼0.0438,
wR2¼0.0644, detailed X-ray crystallographic data is available from
the Cambridge Crystallographic Data Center, 12 Union Road, Cam-
bridge CB2 1EZ, UK (for compound 12 CCDC # 730557).
(dec); IR (KBr):
NMR (400 MHz):
n
3300–3000 (multiple bands), 1682, 1626 cmꢁ1; 1H
d
1.33 (d, 3H, J¼6.8 Hz), 2.70–2.90 (m, 2H), 3.13
(dd, 1H, J¼5.2 Hz and 15.2 Hz), 3.98 (s, 3H), 4.02 (s, 3H), 6.98 (s, 1H),
7.38 (s, 1H), 7.76 (s, 1H), 8.93 (br s, 1H, D2O exchangeable); 13C NMR
4.2.12. 3,5-Diazatetracyclo[12.4.0.02,11.04,9]octadeca-1(14),2(11),3,9,
12,15,17-heptaen-6-one (13). Yield: 51%; Rf (40% EtOAc in hexanes)
0.56; Reaction time: 71 h (70 hþ1 h); mp:197–198 ꢀC (dec); IR
(100 MHz): d 15.58, 32.66, 35.41, 56.07, 56.30, 105.24, 106.99, 117.01,
120.91, 134.00, 142.91, 148.71, 149.07, 152.56, 174.45; LCMS (m/z):
273 (MþH)þ; Anal. Calcd for C15H16N2O3: C, 66.16; H, 5.92; N, 10.29,
Found: C, 66.26; H, 5.86; N, 10.43.
(KBr):
(400 MHz):
n ;
3250–3100 (multiple bands), 1676, 1612 cmꢁ1 1H NMR
d
2.79 (t, 2H, J¼7.2 Hz), 3.17 (t, 2H, J¼7.2 Hz), 7.58–7.78
(m, 4H), 7.88 (d, 1H, J¼6.8 Hz), 7.94 (s, 1H), 8.17 (s, 1H, D2O ex-
4.2.8. 2,4-Diaza-12,13-dimethoxytricyclo[8.4.0.03,8]tetradeca-
1(10),2,8,11,13-pentaen-5-one (9). Yield: 48%; Rf (40% EtOAc in
hexanes) 0.18; reaction time, 71 h (70 hþ1 h); mp: 234–236 ꢀC
changeable), 9.08 (d, 1H, J¼8.0 Hz); 13C NMR (100 MHz):
d 24.37,
30.71, 118.70, 123.35, 124.23, 124.71, 126.07, 126.73, 127.78, 128.02,
130.55, 133.76, 135.23, 144.25, 149.26, 171.51; LCMS (m/z): 249
(MþH)þ; Anal. Calcd for C16H12N2O: C, 77.40; H, 4.87; N, 11.28.
Found: C, 77.30; H, 4.85; N, 11.36.
(dec); IR (KBr):
NMR (400 MHz):
(s, 3H), 4.01 (s, 3H), 6.98 (s, 1H), 7.32 (s, 1H), 7.77 (s, 1H), 8.74 (s, 1H,
D2O exchangeable); 13C NMR (100 MHz):
24.60, 31.01, 56.09,
n
3250–3000 (multiple bands), 1685, 1626 cmꢁ1; 1H
d
2.74 (t, 2H, J¼6.8 Hz), 3.09 (t, 2H, J¼6.8 Hz), 3.99
Crystal data for 13: Empirical formula, C16H12N2O; formula weight,
248.28; crystal color, red color; habit, plate; crystal dimensions,
0.48ꢂ0.34ꢂ0.20 mm3; crystal system, monoclinic; lattice type,
primitive; lattice parameters, a¼6.6279(3) Å, b¼7.5251(4) Å,
d
56.28, 105.31, 107.00, 117.00, 120.98, 133.83, 142.93, 148.85, 149.04,
152.68, 171.65; LCMS (m/z): 259 (MþH)þ; Anal. Calcd’d for
C14H14N2O3: C, 65.11; H, 5.46; N, 10.85. Found: C, 65.00; H, 5.43; N,
10.83.
c¼23.1973(12) Å,
a
¼90.00;
b
¼96.0860(10); ¼90.00; V¼1150.46(10)
g
Å3; space group, p 21/n; Z¼4; Dcalcd¼1.433 g/cm3; F000¼520;
l (Mo-
Ka
)¼0.71073 Å; R (Iꢃ2s1)¼0.0426, wR2¼0.0453, detailed X-ray
4.2.9. 2,4-Diaza-13-ethoxy-12-methoxy-6-methyltricylo-[8.4.0.03,8
]
crystallographic data is available from the Cambridge Crystallo-
graphic Data Center, 12 Union Road, Cambridge CB2 1EZ, UK (for
compound 13 CCDC # 730558).
tetradeca-1(10),2,8,11,13-pentaen-5-one (10). Yield: 56%; Rf (40%
EtOAc in hexanes) 0.34; reaction time; 71 h (70 hþ1 h); mp: 227–
228 ꢀC (dec); IR (KBr):
n 3250–3050 (multiple bands), 1688,
1626 cmꢁ1
;
1H NMR (400 MHz):
d
1.33 (d, 3H, J¼6.0 Hz), 1.53 (t,
Acknowledgements
3H, J¼7.2 Hz), 2.68–2.92 (m, 2H), 3.12 (dd, 1H, J¼4.4 Hz and
15.2 Hz), 3.97 (s, 3H), 4.24 (q, 2H, J¼7.2 Hz), 6.97 (s, 1H), 7.33 (s,
1H), 7.75 (s, 1H), 8.92 (s, 1H, D2O exchangeable); 13C NMR
We thank DST (New Delhi) for funding this project. KRR thanks
CSIR (New Delhi) for his research fellowship. We thank UGC (New
Delhi) for support and for providing some instrumental facilities.
We thank National single crystal X-ray facility funded by DST. We
also thank Professor S. Pal, School of Chemistry, and University of
Hyderabad for helpful discussions regarding X-ray data analysis.
(100 MHz):
d 14.62, 15.56, 32.62, 35.38, 56.09, 64.52, 105.32,
107.54, 116.87, 120.77, 133.96, 142.86, 148.86, 148.92, 151.86,
174.49; LCMS (m/z): 287(MþH)þ; Anal. calcd for C16H18N2O3: C,
67.12; H, 6.34; N, 9.78. Found: C, 67.26; H, 6.36; N, 9.70.
4.2.10. 2,4-Diaza-13-ethoxy-12-methoxytricyclo[8.4.0.03,8]-tetra-
deca-1(10),2,8,11,13-pentaen-5-one (11). Yield: 49%; Rf (40% EtOAc
in hexanes) 0.16; reaction time: 71 h (70 hþ1 h); mp: 247–248 ꢀC
References and notes
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(dec); IR (KBr):
NMR (400 MHz):
n
3250–3050 (multiple bands), 1687, 1626 cmꢁ1; 1H
d
1.46 (t, 3H, J¼6.8 Hz), 2.66 (t, 2H, J¼7.2 Hz), 3.01
(t, 2H, J¼7.2 Hz), 3.90 (s, 3H), 4.17 (q, 2H, J¼6.8 Hz), 6.89 (s, 1H), 7.27
(s, 1H), 7.68 (s, 1H), 8.99 (br s, 1H, D2O exchangeable); 13C NMR
(100 MHz): d 14.63, 24.58, 30.99, 56.11, 64.54, 105.35, 107.57, 116.85,
120.84, 133.80, 142.88, 148.90, 148.99, 151.95, 171.71; LCMS (m/z):
273 (MþH)þ; Anal. Calcd for C15H16N2O3: C, 66.16; H, 5.92; N, 10.29.
Found: C, 66.03; H, 5.96; N, 10.15.
4.2.11. 3,5-Diaza-7-methyltetracyclo[12.4.0.02,11.04,9]ocatdeca-
1(14),2(11),3,9,12,15,17-heptaen-6-one (12). Yield: 59%; Rf (40%
EtOAc in hexanes) 0.70; reaction time: 71 h (70 hþ1 h); mp: 185–
187 ꢀC; IR (KBr):
n 3250–3150 (multiple bands), 1697, 1678,
1616 cmꢁ1; 1H NMR (400 MHz):
d
1.37 (d, 3H, J¼6.8 Hz), 2.73–2.98
(m, 2H), 3.20 (dd, 1H, J¼5.6 Hz and 15.20 Hz), 7.58–7.78 (m, 4H),
7.84–7.92 (m, 1H), 7.93 (s, 1H), 8.13 (s, 1H, D2O exchangeable), 9.08
(d, 1H, J¼8.8 Hz), 13C NMR (100 MHz):
d 15.51, 32.43, 35.21, 118.77,
123.31, 124.19, 124.72, 125.96, 126.72, 127.79, 128.00, 130.56, 133.75,
135.35,144.26, 149.25,174.17; LCMS (m/z): 263 (MþH)þ; Anal. Calcd
for C17H14N2O: C, 77.84; H, 5.38; N, 10.68. Found: C, 77.88; H, 5.37;
N, 10.88.
Crystal data for 12: Empirical formula, C17H14N2O; formula
weight, 262.30; crystal color, colorless; habit, plate; crystal

D. Basavaiah, K.R. Reddy / Tetrahedron 66 (2010) 1215–1219
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11. One of the reviewers has suggested to examine the application of other acids
(other than propanoic acid) for efficiently performing (faster reaction rate) the
Johnson–Claisen rearrangement step. Accordingly, we have carried out the
Johnson–Claisen rearrangement of the compound 1a with triethyl orthopro-
pionate in the presence of other acids such as AcOH, CF3COOH, MeSO3H, and
BF3:OEt2, as catalysts. We noticed that propanoic acid provided better results,
both in terms of yield and rate of the reaction, than the other acids.
12. Detailed X-ray crystallographic data are available from the CCDC, 12 union road,
Cambridge CB2 1EZ, UK; for compound 12 (CCDC # 730557) and for compound
13 (CCDC # 730558).
7. Rao and co-worker have reported synthesis of [1,8]naphthyridine-3-carboxyl-
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13. The single crystal X-ray structure revealed the presence of two molecules in the
asymmetric unit in the case of compound 12. For clarity we have shown one
molecule in the ORTEP diagram (Fig. 2).