Synthesis and conformational analysis of naphthylnaphthoxazine derivatives

Article abstract of DOI:10.1016/j.molstruc.2009.04.015

Four new primary aminonaphthols (4, 5, 9 and 10) were synthesized from 1- or 2-naphthol and 1- or 2-naphthaldehyde via naphthoxazines in modified Mannich condensations. Simple ring-closure reactions of these aminonaphthols with paraformaldehyde, 4-nitrobe

Full text of DOI:10.1016/j.molstruc.2009.04.015

Journal of Molecular Structure 929 (2009) 58–66
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis and conformational analysis of naphthylnaphthoxazine derivatives
Diána Tóth a,b, István Szatmári a,b, Matthias Heydenreich c, Andreas Koch c,
Erich Kleinpeter c, Ferenc Fülöp a,b,
*
a Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6., Hungary
b Research Group for Stereochemistry Hungarian Academy of Sciences, University of Szeged, H-6720 Szeged, Eötvös u. 6., Hungary
c Department of Chemistry, University of Potsdam, P.O. Box 691553, D-14415 Potsdam, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Four new primary aminonaphthols (4, 5, 9 and 10) were synthesized from 1- or 2-naphthol and 1- or 2-
naphthaldehyde via naphthoxazines in modified Mannich condensations. Simple ring-closure reactions
of these aminonaphthols with paraformaldehyde, 4-nitrobenzaldehyde, phosgene or 4-chlorophenyl iso-
thiocyanate led to new heterocyclic derivatives. In these transformations, either an sp2 or an sp3 carbon
was inserted between the hydroxy and amino groups. The effects of substituents and the naphthyl ring on
the conformation were investigated by means of NMR measurements, employing both dipolar and scalar
couplings. The structures were confirmed by DFT quantum chemical calculations involving computed
coupling constants, intramolecular distances between nuclei and the relative energies of the preferred
conformers.
Received 26 March 2009
Received in revised form 6 April 2009
Accepted 7 April 2009
Available online 18 April 2009
Keywords:
Aminonaphthols
Naphthoxazines
Conformational analysis
DFT calculations
NBO analysis
Ó 2009 Elsevier B.V. All rights reserved.
1. Introduction
amidomethyl-2-naphthols [10–12]. Through the use of aliphatic
aldehydes, e.g. formaldehyde [13], acetaldehyde, propionaldehyde,
The chemistry of the Betti bases dates from the beginning of the
20th century, when Betti reported the synthesis of 1-( -aminoben-
zyl)-2-naphthol [1,2]. The three-component modified Mannich
reaction involving 2-naphthol, benzaldehyde and ammonia re-
sulted in 1,3-diphenylnaphthoxazine, which was subsequently
butyraldehyde, isobutyraldehyde and pivalaldehyde, 1-(1-amino-
alkyl)-2-naphthols have been synthesized [14,15], while from het-
eroaromatic aldehydes primary aminonaphthols have been
prepared and their ring-chain tautomeric behaviour has been stud-
ied [16].
a
hydrolysed to 1-(
a
-aminobenzyl)-2-naphthol.
Our present aim was to prepare new primary aminonaphthols
from 1- or 2-naphthol and 1- or 2-naphthaldehyde and to extend
the applicability of these compounds for the preparation of new
heterocyclic derivatives by simple ring-closure reactions with
paraformaldehyde, 4-nitrobenzaldehyde, phosgene or 4-chloro-
phenyl isothiocyanate. We additionally investigated the influence
of the substituents at position 3 or 2 and the connecting position
of the naphthalene ring on the conformation.
The reaction can be extended by using chiral amines instead of
ammonia, which furnishes non-racemic N-substituted aminonaph-
thol derivatives; this opened up a new area of application of these
enantiopure compounds as chiral ligands in asymmetric transfor-
mations [3–7]. As a result of an integrated, virtual database screen-
ing, 7-[anilino(phenyl)methyl]-2-methyl-8-quinolinol was found
to represent a promising new class of non-peptide inhibitors of
the MDM2–p53 interaction [8].
Interest in the synthesis of primary aminonaphthols has greatly
increased during the past few years following an evaluation of the
hypotensive and bradycardiac effects of 1-aminomethyl-2-naph-
thol derivatives [9], and the synthesis of a wide variety of such
compounds were recently achieved through the hydrolysis of 1-
2. Results and discussion
2.1. Syntheses
The aminonaphthols 4, 5, 9 and 10 were prepared via the reac-
tions of the corresponding 1- or 2-naphthol with 1- or 2-naphthal-
dehyde in the presence of methanolic ammonia solution in
absolute methanol at room temperature for 24 h. This led to the
naphthoxazines 2, 3, 7 and 8 (Scheme 1: i), acidic hydrolysis of
which gave the desired aminonaphthol hydrochlorides 4, 5, 9 and
10 (Scheme 1: ii). Because of the instability of the aminonaphthyl
* Corresponding author. Address: Institute of Pharmaceutical Chemistry, Univer-
sity of Szeged, and Research Group for Stereochemistry Hungarian Academy of
Sciences, Eotvos u 6, H-6720 Szeged, Hungary. Tel.: +36 62 545564; fax: + 36 62
545705
E-mail address: fulop@pharm.u-szeged.hu (F. Fülöp).
0022-2860/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2009.04.015

D. Tóth et al. / Journal of Molecular Structure 929 (2009) 58–66
59
H
R
NH2 HCl
OH
R
N
R
OH
i
ii
+
R-CHO
O
1
2, 3
4, 5
R
OH
OH NH2 HCl
R
O
NH
i
ii
+
R-CHO
R
6
7, 8
9, 10
R = 2-naphthyl: 2, 4 (87%), 7, 9 (32%)
R = 1-naphthyl: 3, 5 (28%), 8, 10 (42%)
Scheme 1. Reagents and conditions: (i) NH3/MeOH, r.t.; (ii) 60 °C for 2–3 h, HCl/H2O.
naphthol derivatives, compounds 4, 5, 9 and 10 were isolated as
O
their hydrochlorides, in moderate to good yields (28–87%).
In the first stage of the transformations of 4, 5, 9 and 10 to het-
erocyclic derivatives, an sp2 carbon (C-3 or C-2) was inserted be-
tween the hydroxy and amino groups (Schemes 2 and 3).
When aminonaphthols 4, 5, 9 and 10 were treated with COCl2 in
the presence of Na2CO3 in toluene/H2O solution at room tempera-
ture for 10 min., the corresponding naphthoxazin-3-ones 11 and
12 and naphthoxazin-2-ones 19 and 20 were formed, in moderate
yields (40–86%) in each case (Schemes 2 and 3: i).
1O2 NH
O
NH
3
i
iv
9, 10
10
7
10b
4
R
10a
6a
9
R
4a
5
8
ii
6
19, 20
25
Cl
Cl
S
For the preparation of 3- and 2-(4-chlorophenylimino)-substi-
tuted naphthoxazines 15, 16, 23 and 24, aminonaphthols 4, 5, 9
and 10 were reacted with 4-chlorophenyl isothiocyanate (Schemes
2 and 3: ii). Thioureas 13, 14, 21 and 22 were converted to the cor-
responding S-methylisothiourea derivatives with methyl iodide,
and subsequent treatment with methanolic KOH gave the corre-
sponding 3- or 2-arylimino-substituted naphthoxazines 15, 16,
23 and 24, in good yields (67–82%), via methyl mercaptan elimina-
tion (Schemes 2 and 3: iii).
N
iii
N
H
OH HN
O
NH
R
R
21, 22
R = 2-naphthyl:
23, 24
19
(78%),
21
23
(40%),
(65%),
24
(67%)
25
(74%), (37%)
20
22
R = 1-naphthyl:
(72%),
Scheme 3. Reagents and conditions: (i) COCl2, toluene/H2O, Na2CO3, 10 min; r.t.;
(ii) 4-Cl-PhNCS, Et3N, toluene, r.t.; (iii) MeI, KOH, MeOH, r.t.; (iv) paraformaldehyde,
Et3N, CHCl3, 6 h, r.t
H
N
H
N
2
R
O
R
1
3
iv
i
10
7
10b
4, 5
4
10a
O
O
9
8
The ring closures of aminonaphthols 4, 5, 9 and 10 with oxo
compounds (i.e. the insertion of an sp3 carbon) resulted in
naphthoxazines.
4a
5
6a
ii
11,612
17, 18
The reactions of aminonaphthols 4, 5 and 10 with paraformal-
dehyde under mild conditions (at room temperature for 6 h) gave
the corresponding 3- and 2-unsubstituted naphthoxazines 17, 18
and 25 in yields of 37–49% (Schemes 2 and 3: iv). The correspond-
ing reaction of 9 did not lead to the desired naphthoxazine. After a
reaction time of 3 h TLC demonstrated that no starting material re-
mained, and the TLC plots observed suggested the rapid decompo-
sition of the expected naphthoxazine derivative.
The analogous reactions of 4, 5, 9 and 10 with 4-nitrobenzalde-
hyde were accomplished under mild conditions. The products 27,
28, 31 and 32 were separated from the reaction mixture in good
yields (78–84%, Scheme 4: i). Compounds 27–29 and 31–33 in
solution can participate in three-component ring-chain tautomeric
equilibria involving the C-3 (27–29) or C-2 (31–33) epimeric naph-
thoxazines (B and C) and the open tautomer (A). The tautomeric
behaviour (the tautomeric ratios) of 27–29 and 31–33 depend on
substituent R at position 1 or 4, and on the properties of the solvent
in question, as revealed in Table 1 [13].
Cl
H
S
N
R
NH
OH
iii
H
N
Cl
R
N
O
13, 14
15, 16
R = 2-naphthyl: 11 (86%), 13 (82%), 15 (76%), 17 (49%)
R = 1-naphthyl:
12 14 16 18
(42%)
(44%),
(80%),
(82%),
Scheme 2. Reagents and conditions: (i) COCl2, toluene/H2O, Na2CO3, 10 min. r.t.; (ii)
4-ClC6H5NCS, Et3N, toluene, r.t.; (iii) MeI, KOH, MeOH, r.t.; (iv) paraformaldehyde,
Et3N, CHCl3, 6 h, r.t.

60
D. Tóth et al. / Journal of Molecular Structure 929 (2009) 58–66
NO2
NO2
NO2
R
NH2 HCl
OH
H
N
H
N
R
R
N
R
i
O
OH
O
4, 5, 26
27-29 B
27-29 B
27-29 B
4 27
,
5 28
,
26 29
,
R = 2-naphthyl:
(84%); R = 1-naphthyl:
(80%); R = phenyl:
NO2
NO2
NO2
OH NH2 HCl
R
i
O
NH
OH
N
O
NH
R
R
R
9, 10, 30
27-29 B
27-29 B
10 32
27-29 B
30 33
9 31
R = 2-naphthyl:
,
(78%); R = 1-naphthyl:
,
(80%); R = phenyl:
,
Scheme 4. Reagents and conditions: (i) 4-nitrobenzaldehyde, Et3N, MeOH, 10 min., r.t.
For 27–29, the predominant form is the trans tautomer (B). The
check particularly on the conformation of the (unsaturated) oxa-
zine ring moiety. The same procedure was applied in the event
of additional substitution at C-3 in the 2-naphthoxazines and at
C-2 in the 1-naphthoxazines, of the sp2 hybridization of C-2 or C-
4. The complete agreement of the computed structures (the pre-
ferred conformers) and the NMR parameters is strong evidence of
the correctness of the calculated geometries of the compounds
studied.
portion of B decreases in the sequence 27 > 28 > 29, while that of
the cis form (C) displays the opposite tendency (Table 1: entries
1–3). This can be explained in terms of steric hindrance. Relative
to CDCl3, the more polar solvent DMSO causes a small increase in
the proportion of the open-chain form (A) at the expense of form
(C) for 29 (Table 1: entry 3), but the main tendency was found to
be similar with that discussed above.
For 31–33 in CDCl3, the steric hindrance of the aryl substituents
at position 4 must exert the most important effect as regards the
composition of the tautomeric mixture and, similar as for 1,3-
disubstituted naphth[1,2-e][1,3]oxazines, the phenyl ring (smaller
then the naphthyl ringsystem) resulted in more form (C) and less
form (B) (Table 1: entries 4–6).
The effect of the change of the solvent seems to be somewhat
more marked for 31–33 (Table 1: entries 4–6) than for 27–29 (Ta-
ble 1: entries 1–3).
Both the 1- and 2-naphthyl substituents at C-1 in the 2-naph-
thoxazines and at C-4 in the 1-naphthoxazines, respectively, were
found to have only marginal influence on the conformational equi-
libria, whereas in the trans isomers of the disubstituted 1- and 2-
naphthoxazines 27, 28, 31 and 32 they do influence the preference
for the corresponding S/R and R/S diastereomers, respectively (vide
infra).
2.2.1. Compounds with sp3 C-2 or C-3 atoms
Compounds which are only mono-substituted with 1- and 2-
naphthyl substituents at C-1 and C-4, respectively (17, 18 and
25), prefer twisted-chair conformers (cf. the global minimum-en-
ergy structure of 17, for instance, in Fig 1). The analogue of 17
could not be obtained experimentally, but was computed at the
DFT level of theory; the same twisted-chair conformer as in 17,
18 and 25 was found to be preferred.
2.2. Conformational analysis
Theoretical calculations were performed on the compounds
studied and their global minimum-energy structures were deter-
mined. These structures were compared with the relevant NMR
spectroscopic data (NOEs and vicinal H,H-coupling constants) to
This preferred conformation (cf. 17 in Fig. 1) proves to be in
excellent agreement with the experimental NMR data: NOEs were
observed between H-1 and NH (the corresponding distance was
computed to be only 2.243 Å) and between NH and H-3eq (com-
puted distance ꢀ2.360 Å). Moreover, the corresponding scalar vic-
inal 3JH,H coupling constants were 5.0 Hz (3JH1,NH computed 4.7 Hz,
dihedral angle 43.3°), 3.9 Hz (3JH-3eq,NH computed 3.2 Hz, dihedral
angle ꢀ57.3°), and 13.6 Hz (3JH-3ax,NH computed 13.1 Hz, dihedral
angle ꢀ178.2°). The corresponding NMR data of 18 are given in Ta-
ble 2 and are likewise seen to be in excellent agreement with the
computed values.
Table 1
Proportions of tautomers (%) in 27–29 and 31–33.
Entry
Comp.
CDCl3
DMSO
A
B
C
A
B
C
1
2
3
4
5
6
27
28
–
–
3.1
13.8
4.5
14.9
100.0a
95.4
86.1
68.9
77.6
50.1
–
4.6
10.8
17.3
17.9
35.0
–
–
15.0
34.3
–
100.0
94.8
84.8
46.1
82.8
42.6
–
5.2
0.2
19.6
17.2
20.5
29b
31
32
33c
36.9
A twisted-chair conformer was also found for 25 (cf. Fig. 2). As
for 17 and 18, a similar 3JH,H value in the O(2)CH2ANH–C(4)H cou-
pling fragment and similar NOEs between NH and H-2eq and H-4,
respectively, were observed (cf. Table 2).
a
Either the population of tautomers A and C is too low to be detected by NMR, or
the equilibration is fast on the NMR time scale (see text below).
b
Data from Ref. [17].
Data from Ref. [18].
c

D. Tóth et al. / Journal of Molecular Structure 929 (2009) 58–66
61
and 4.9 Hz in 28B] agree well with the computed values [e.g. 27B:
12.5 Hz (3JH-2,H-3) and 4.8 Hz (3JH-1,H-2)]. Surprisingly, a strong NOE
was found between H-3 and NAH, which are in trans position. This
dipolar coupling, however, should be near to zero in 27B, but some
27C may be present in marginal concentration or in rapid equilib-
rium with B on the NMR time-scale; obviously, the reaction rate al-
lows NOE transfer between the tautomeric species (cf. Table 1).
The main tautomers 31B and 32B also occur in a twisted-chair
conformation, as illustrated for 32B in Fig. 4. This calculated min-
imum-energy structure is corroborated by the experimentally
3
determined coupling constants JH-3,H-4 = 5.7 Hz (computed dihe-
3
dral angle 40.4°) and JH-2,H-3 = 13.5 Hz (computed dihedral angle
177.6°) and the corresponding NOEs, which were found to be
strong between NAH and H-4 (computed distance 2.243 Å) and
weak between H-2 and NAH (2.902 Å).
Surprisingly, in 27, 28 and 32 the S/R diastereomer proved to be
more stable than the R/S analogue; the reverse situation was the
case for 31.
2.2.2. Compounds with sp2 C-2 or C-3 atoms
Introduction of an sp2 carbon at position 3 (11 and 12) or 2 (19
and 20) obviously leads to very similar conformational behaviour;
in accordance with this, very similar minimum-energy conforma-
tions of all of these compounds were calculated: the oxazine ring
is nearly flat with a slight boat conformation (cf. Fig. 5). Only in
Fig. 1. Energy-minimum structure of (1S)-17.
If the compounds are additionally substituted at C-3 (b-naph-
thoxazines) or C-2 (a-naphthoxazines), tautomeric equilibria re-
3
sult (cf. Scheme 4). The major ring form B was isolated and
studied by NMR spectroscopy. In contrast with the simple R/S chi-
rality in 17, 18 and 25, which does not influence the NMR spectra
in achiral media, in 28, 29, 31 and 32 R/S and S/R diastereomers
have to be considered.
The global minimum-energy structure of the major ring form B
is characterized by the trans arrangement of H-3 and NAH (as de-
picted in Fig. 3 for 27B) and prefers the twisted-chair conformation.
The experimentally determined vicinal H,H-coupling constants 3JH-
2,H-3 [14.0 Hz in 27B and 13.6 Hz in 28B] and 3JH-1,H-2 [5.2 Hz in 27B
one case (11) could the JNH,CH coupling constant be detected; it
was 2.9 Hz. The corresponding signals of the other compounds
were more or less broadened and the corresponding vicinal cou-
3
pling constants could not be extracted. The magnitude of JNH,CH
was in good agreement with the calculated values. These were in
the range 0–1.8 Hz, with calculated dihedral angles of 59.6–71.1°,
both characteristic of the syn-clinal conformation of the NHACH
moiety. The distance between these two hydrogens was computed
to be in the range 2.43–2.56 Å, which corresponds to the mean
NOEs determined in these compounds.
Table 2
Experimental and computed coupling constants and some calculated dihedral angles and distances for compounds 18 and 25.
Compound 3JNCH–NH
(exp) (Hz) (calc) (Hz) angle
NCHANH
3JNCH–NH
Dihedral
3JNH–OCHeq
(exp) (Hz)
3JNH–OCHeq
(calc) (Hz)
Dihedral
angle NH–
OCHeq
3JNH–
3JNH–OCHax
(calc) (Hz)
Dihedral
angle
NHAOCHax
Distance
NCHANH
(Å)
Distance
NHAOCHeq
(Å)
OCHax
(exp)
18
25
4.9
6.2
4.8
4.7
42.8°
41.6°
3.7
5.4
3.1
2.0
ꢀ57.7°
ꢀ58.0°
13.9
12.2
13.1
13.2
ꢀ178.6°
ꢀ179.0°
2.241
2.242
2.358
2.359
Fig. 2. Minimum-energy structure of (4S)-25.

62
D. Tóth et al. / Journal of Molecular Structure 929 (2009) 58–66
Fig. 3. Minimum-energy structure of (1S,3R)-27B.
Fig. 4. Minimum-energy structure of (2R,4S)-32B.
For compounds 15, 16, 23 and 24 the endocyclic/exocyclic tau-
tomerism of the C@N double bond is possible. The energy levels
indicated the presence of the exocyclic form (Schemes 2 and 3).
This was supported by the NMR data: NOE interactions were found
between NAH and the corresponding CAH at position 1 (15 and
Fig. 5. Minimum-energy structure of (4R)-11.
16) or 4 (23 and 24). Ab initio calculations on the title compounds
pointed to the presence of the E isomers.
Fig. 6. Minimum-energy structure of (4R)-23.

D. Tóth et al. / Journal of Molecular Structure 929 (2009) 58–66
63
The oxazine ring in 15, 16, 23 and 24 turned out to be nearly
planar; the minimum-energy structure of 23 is shown in Fig. 6.
4.1.1. 1-[Aminomethyl-(2-naphthyl)]-2-naphthol hydrochloride (4)
White crystals, yield 7.29 g (87%), m.p. 193–195 °C. 1H NMR
(DMSO-d6) d 6.45 (H: CH, 1H, s), 7.35 (H: 8, 1H, t, J = 7.5 Hz), 7.46
(H: 3, 1H, d, J = 8.9 Hz), 7.48–7.55 (H: 70, 10, 2H, m), 7.59 (H: 60,
1H, d, J = 7.5 Hz), 7.85–7.91 (H: 4, 40, 80, 30, 50, 5, 6H, m), 8.07 (H:
7, 1H, s), 8.10 (H: 6, 1H, d, J = 8.6 Hz), 9.05 (H: NH3, 3H, s), 11.06
(H: OH, 1H, s) ppm. 13C NMR (DMSO-d6): d 51.0 (C: CH), 113.7
(C: 1), 118.7 (C: 3), 121.9 (C: 6), 123.0 (C: 8), 125.2 (C: 60), 125.9
(C: 7), 126.5 (C: 70), 126.7 (C: 10), 127.3 (C: 40), 127.6 (C: 80),
127.9 (C: 50), 128.2 (C: 4a, 30), 128.9 (C: 5), 130.8 (C: 4), 131.9 (C:
4a0), 132.4 (C: 8a), 132.5 (C: 8a0), 135.1 (C: 20), 153.9 (C: 2) ppm.
C21H18ClNO (335.83): calcd. C 75.11, H 5.40, N 4.17; found C
75.05, H 5.41, N 4.18.
3. Conclusions
Four new aminomethylnaphthols (4, 5, 9 and 10) were synthe-
sized by the condensation of 1- or 2-naphthol with 1- or 2-naph-
thaldehydes in the presence of ammonia, followed by acidic
hydrolysis. The condensation of 4, 5, 9 and 10 with paraformalde-
hyde, 4-nitrobenzaldehyde, phosgene or 4-chlorophenyl isothiocy-
anate led to naphthoxazine derivatives. Compounds 27–29 and
31–33 in solution proved to be three-component tautomeric mix-
tures. The tautomeric ratio influenced by the steric hindrance of
the aromatic rings at position 1 or 4 and by the connecting position
of the naphthyl rings at the same positions. The conformational
analysis revealed that the conformation of the oxazine ring moiety
depends on the hybridization of the carbon at position 3 or 2. The
compounds containing an sp3 carbon preferred a twisted-chair
conformation, whereas the insertion of an sp2 carbon led to a
nearly flat naphthoxazine ring moiety.
4.1.2. 1-[Aminomethyl-(1-naphthyl)]-2-naphthol hydrochloride (5)
White crystals, yield 2.34 g (28%), m.p. 202–204 °C. 1H NMR
(DMSO-d6): d 6.96 (H: CH, 1H, s), 7.25 (H: 20, 1H, t, J = 7.1 Hz),
7.33 (H: 40, 1H, t, J = 7.4 (H: 3, 1H, d, J = 16.0 Hz), 7.51–7.55 (H:
30, 60, 2H, m), 7.79–7.88 (H: 6, 70, 80, 7, 50, 5H, m), 7.92–7.97 (H:
4, 5, 2H, m), 8.31–8.32 (H: 8, 1H, m), 8.96 (H: NH3, 3H, s), 11.92
(H: OH, 1H, s) ppm. 13C NMR (DMSO-d6): d 48.3 (C: CH), 113.8
(C: 1), 118.8 (C: 3), 121.8 (C: 6), 122.9 (C: 8), 123.2 (C: 20), 125.2
(C: 60), 126.1 (C: 70), 126.2 (C: 80), 126.9 (C: 30), 127.1 (C: 40),
128.3 (C: 4a), 128.9 (C: 4), 128.9 (C: 5), 129.1 (C: 7), 130.1 (C:
8a0), 130.9 (C: 50), 131.9 (C: 8a), 133.1 (C: 4a0), 133.5 (C: 10),
154.2 (C: 2) ppm. C21H18ClNO (335.83): calcd. C 75.11, H 5.40, N
4.17; found C 75.15, H 5.42, N 4.19.
4. Experimental
Melting points were determined on a Kofler micro melting
apparatus and are uncorrected. Merck Kieselgel 60F254 plates were
used for TLC.
The NMR spectra were recorded in DMSO-d6 (unless specified as
CDCl3) solution in 5 mm tubes, at room temperature, on a BRUKER
AVANCE 500 spectrometer at 500.17 (1H) and 125.78 (13C) MHz,
with the deuterium signal of the solvent as the lock and TMS as
the internal standard for 1H or the solvent as the internal standard
for 13C. All spectra (1H, 13C, gs-H,H-COSY, gs-HMQC, gs-HMBC, and
NOESY) were acquired and processed with the standard BRUKER
software.
Geometry optimizations were performed without restrictions,
using the Gaussian 03 version C.02[19] program package. Different
conformation and configurations of all studied compounds were
preoptimized by using the PM3 Hamiltonian [20,21]. Density func-
tional theory calculations were carried out at the B3LYP/6-31G**
[22,23] level of theory. Stationary points on the potential
hypersurface were characterized by force constants. Coupling con-
stants were computed at the same theory level, B3LYP/6-31G**
[24,25].
4.1.3. 2-[Aminomethyl-(2-naphthyl)]-1-naphthol hydrochloride (9)
White crystals, yield 2.69 g (32%), m.p. 168–171 °C. 1H NMR
(DMSO-d6): d 6.32 (H: HCANH3, 1H, s), 7.51–7.57 (H: 7, 6, 30, 80,
60, 5H, m), 7.63–7.56 (H: 5, 4a0, 2H, m), 7.86–7.88 (H: 70, 1H, m),
7.89–7.95 (H: 4, 50, 40, 3H, m), 8.09 (H: 10, 1H, s), 8.35 (H: 8, 1H,
dd, J = 6.20 Hz), 9.27 (H: NH3, 3H, s), 10.17 (H: OH, 1H, s) ppm.
13C NMR (DMSO-d6): d 52.1 (C: HCANH3), 119.5 (C: 2), 120.1 (C:
50), 122.6 (C: 8), 124.9 (C: 3), 125.3 (C: 80), 125.3 (C: 8a0), 125.6
(C: 70), 125.6 (C: 10), 126.6 (C: 20), 126.8 (C: 6, 40), 127.6 (C: 4),
127.8 (C: 6), 127.9 (C: 60), 128.4 (C: 30), 132.4 (C: 4a0), 132.5 (C:
8a), 134.0 (C: 4a), 135.7 (C: 2), 150.0 (C: 1) ppm. C21H18ClNO
(335.83): calcd. C 75.11, H 5.40, N 4.17; found C 75.12, H 5.39, N
4.16.
4.1.4. 2-[Aminomethyl-(1-naphthyl)]-1-naphthol hydrochloride (10)
White crystals, yield 3.52 g (42%), m.p. 161–164 °C. 1H NMR
(DMSO-d6): d 6.87 (H: HC. 1H, s), 7.25 (H: 3, 1H, d, J = 8.7 Hz),
7.34 (H: 4, 1H, d, J = 8.7 Hz), 7.47–7.56 (H: 80, 60, 50, 7, 4H, m),
7.68 (H: 30, 1H, t, J = 7.7 Hz), 7.78 (H: 6, 1H, d, J = 7.5 Hz), 7.94–
7.98 (H: 40, 70, 2H, m), 8.03–8.06 (H: 5, 20, 2H, m), 8.45 (H: 8, 1H,
d, J = 8.2 Hz), 9.23 (H: NH3, 3H, s), 10.54 (H: OH, 1H, s) ppm. 13C
NMR (DMSO-d6): d 48.3 (C: CH), 119.0 (C: 2), 120.0 (C: 4), 122.9
(C: 5,8), 123.6 (C: 20), 125.2 (C:30), 125.4 (C: 3), 125.4 (C: 8a),
125.6 (C: 80), 126.2 (C: 50), 126.9 (C: 60), 126.9 (C: 7), 127.7 (C: 6),
128.7 (C: 40), 128.9 (C: 70), 129.8 (C: 4a0), 133.4 (C: 10), 133.8 (C:
8a0), 134.2 (C: 4a), 150.0 (C: 1) ppm. C21H18ClNO (335.83): calcd.
C 75.11, H 5.40, N 4.17; found C 75.11, H 5.45, N 4.16.
Different starting conformations were created and the results
were analysed and displayed by using the molecular modelling
program SYBYL 7.3 [26] and the program GaussView 2.0. [27] Dif-
ferent local minimum-energy conformations were selected to ana-
lyse the relative stability and the geometrical parameter.
Results were calculated on a SGI and on a Linux cluster.
4.1. General method for the synthesis of
aminomethylnaphthylnaphthols (4, 5, 9 and 10)
To a solution of 1- or 2-naphthol (3.6 g, 25 mmol) in absolute
MeOH (30 mL), the appropriate 1- or 2-naphthaldehyde (9.75 g,
62.5 mmol) and 25% methanolic ammonia solution (20 mL) were
added. The mixture was allowed to stand at room temperature
for 48 h. The solvent was removed under reduced pressure and
10% aq. HCl (210 mL) was added to the residue. The mixture was
stirred and heated for 3 h at 60 °C, and the solvent was evaporated
off. The crystalline hydrochloride of 4, 5, 9 or 10 that separated out
from EtOAc (50 mL) was filtered off, washed with CHCl3 and Et2O,
and recrystallized from Et2O–MeOH (4:1).
4.2. General method for the synthesis of naphthylnaphthoxazinones
(11, 12, 19 and 20)
Aminonaphthol 4, 5, 9 or 10 (0.50 g, 1.49 mmol) was dissolved
in toluene–H2O 1:1 (50 mL), phosgene (0.32 mL; 20% in toluene,
1.64 mmol) and sodium carbonate (0.69 g, 1.64 mmol) were added.
The mixture was stirred at r.t. for 10 min. and the resulting white
precipitate was filtered off and recrystallized from iPr2O (30 mL).

64
D. Tóth et al. / Journal of Molecular Structure 929 (2009) 58–66
4.2.1. 1-(2-Naphthyl)-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazin-3-
one (11)
uene (10 mL) was stirred at room temperature for 6 h. The crystals
that separated out were filtered off and washed with toluene
(2 ꢁ 10 mL). The product was purified by column chromatography
(silica gel, eluent: n-hexane–EtOAc, 3:1).
White crystals, yield 0.42 g (86%), m.p. 260–264 °C. 1H NMR
(DMSO-d6): d 7.01 (H: 20, 1H, d, J = 7.1 Hz), 7.13 (H: 1, 1H, s), 7.31
(H:70; 1H, s), 7.33 (H: 30, 1H, d, J = 3.8 Hz), 7.37 (H: 40, 1H, d,
J = 7.2 Hz), 7.41 (H: 60, 1H, t, J = 8.1 Hz), 7.47 (H: 6, 1H, d,
J = 8.9 Hz), 7.65 (H: 8, 1H, t, J = 7.3), 7.74 (H: 9, 1H, t, J = 7.2 Hz),
7.88 (H: 80, 1H, d, J = 8.1 Hz), 7.96 (H 50, 1H, d, J = 8.1 Hz), 8.02
(H: 7, 1H, d, J = 8.1 Hz), 8.05 (H: 5, 1H, d, J = 9.0 Hz), 8.95 (H: NH,
1 H, d, J = 2.9 Hz) ppm. 13C NMR (DMSO-d6): d 49.7 (C: CH), 114.0
(C: 10b), 116.9 (C: 6), 122.8 (C: 60), 123.5 (C: 10), 125.1 (C: 70),
125.3 (C: 20), 125.9 (C: 40), 126.3 (C: 30), 126.0 (C: 9), 127.4 (C:
30), 128.7 (C: 7), 128.8 (C: 50), 128.8 (C: 80), 129.1 (C: 8a0), 130.0
(C: 10), 130.4 (C: 10a), 130.5 (C: 4a0), 133.7 (C: 6a), 148.1 (C: 3),
149.3 (C: 4a) ppm. C22H15NO2 (325.36): calcd. C 81.21, H 4.65, N
4.30; found C 81.28, H 4.66, N 4.28.
4.3.1. N1-[ -(1-hydroxynaphth-2-yl)naphth-2-yl-methyl]-N2-(4-
a
chlorophenyl)thiourea (21)
Light-yellow crystals, yield 0.26 g (65%), m.p. 125–129 °C. 7.32–
7.51 (H: 4, 10, 70, 8, 80, 30, 7, 200, CH, 10H, m), 7.63 (H: 40, 6, 2H, d,
J = 15.0 Hz), 7.77 (H: 3, 1H, s), 7.83–7.91 (H: 300, 50, 5, 4H, m),
8.22–8.25 (H: 60, 1H, m), 8.78 (H: CHNH, 1H, d, J = 13.9 Hz), 9.69
(H: CNH, 1H, s), 9.87 (H: OH, 1H, s) ppm. 13C NMR (DMSO-d6): d
56.4 (C: HCANH), 119.8 (C: 4), 122.1 (C: 60), 123.4 (C: 2, 8a),
124.2 (C: 40), 124.7 (C: 3), 125.1 (C: 6), 125.4 (C: 4a), 125.7 (C:
10), 125.8 (C: 70), 126.0 (C: 8), 126.2 (C: 80, 30), 126.4 (C: 7), 127.5
(C: 5), 127.7 (C: 300), 127.9 (C: 50), 128.4 (C: 200), 132.0 (C: 4a0, 20),
132.8 (C: 400), 133.7 (C: 8a0), 138.7 (C: 4a0), 140.0 (C: 100), 149.6
(C: 1), 180.2 (C: CS) ppm. C28H21ClN2OS (469.00): calcd. C 71.71,
H 4.51, N 5.97; found C 71.78, H 4.50, N 5.98.
4.2.2. 1-(1-Naphthyl)-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazin-3-
one (12)
White crystals, yield 0.21 g (44%), m.p. 262–265 °C. 1H NMR
(DMSO-d6) d 6.38 (H: 1, 1H, s), 7.39–7.49 (H: 30, 60, 50, 6, 4H, m),
7.49–7.53 (H: 8, 80, 2H, m), 7.85–7.89 (H: 40, 7, 9, 70, 4H, m), 7.93
(H: 10, 1H, s), 7.95 (H: 10, 1H, d, J = 7.6 Hz), 8.03 (H: 5, 1H, d,
J = 9.0 Hz), 8.95 (H: 2, 1H, d, J = 2.9 Hz) ppm. 13C NMR (DMSO-d6):
d 55.6 (C: 1), 115.1 (C: 10a), 118.4 (C: 6), 124.5 (C: 70), 126.1 (C:
30), 126.5 (C: 50), 127.3 (C: 10), 127.9 (C: 8), 128.1 (C: 80), 128.8 (C:
60), 128.9 (C: 40), 129.4 (C: 7), 130.1 (C: 10), 130.4 (C: 9), 130.5 (C:
6a), 131.9 (C: 5), 131.9 (C: 8a0), 133.9 (C: 4a0), 134.1 (C: 20), 141.3
(C: 10b), 148.6 (C: 4a), 150.8 (C: 3) ppm. C22H15NO2 (325.36): calcd.
C 81.21, H 4.65, N 4.30; found C 81.23, H 4.63, N 4.29.
4.3.2. N1-[ -(1-hydroxynaphth-2-yl)naphth-1-yl-methyl]-N2-(4-
a
chlorophenyl)thiourea (22)
Light-yellow crystals: yield 0.29 g (72%), m. p. 158–160 °C. 1H
NMR (DMSO-d6): d 7.30–7.34 (C: 200, 2, 5, 4H, m), 7.43–7.56 (C: 6,
70, 80, 30, 40, 8, 6H, m), 7.63 (C: H: 300, 2H, d, J = 8.5 Hz), 7.82–7.89
(C: CH, 3, 60, 3H, m), 7.95 (H: 2, 1H, d, J = 7.9 Hz), 8.23–8.26 (H:
2, 7, 2H, m), 8.67 (H: HCANH, 1H, d, J = 7.7 Hz), 9.63 (H: OH, 1H,
s), 9.75 (H: HNASC, 1H, s) ppm. 13C NMR (DMSO-d6): d 52.7 (C:
CH), 119.6 (C: 4), 122.1 (C: 7), 123.0 (C: 2), 123.8 (C: 300), 124.3
(C: 20), 125.1 (C: 6), 125.2 (C: 4a), 125.3 (C: 5), 125.8 (C: 70, 80),
125.9 (C: 30), 126.3 (C: 40), 127.4 (C: 8a), 127.7 (C: 3, 60), 128.2
(C: 200), 128.6 (C: 8), 131.0 (C: 4a0), 133.5 (C: 8a0), 133.7 (C: 10),
138.2 (C: 400), 138.8 (C: 100), 149.4 (C: 1), 179.8 (C: CS) ppm.
C28H21ClN2OS (469.00): calcd. C 71.71, H 4.51, N 5.97; found C
71.74, H 4.51, N 5.97.
4.2.3. 4-(2-Naphthyl)-2,3-dihydro-1H-naphth[2,1-e][1,3]oxazin-2-
one (19)
White crystals, yield 0.19 g (40%), m.p. 227–232 °C. 1H NMR
(DMSO-d6): d 6.04 (H: 4, 1H, s), 7.20 (H: 5, 1H, d, J = 8.4 Hz), 7.49
(H: 10, 1H, d, J = 8.4 Hz), 7.51–7.56 (H: 400, 50, 2H, m), 7.59–7.68
(H: 9, 7, 6, 3H, m), 7.89–7.96 (H: 80, 70, 60, 8, 30, 5H, m), 8.24 (H:
10, 1H, d, J = 8.3 Hz), 8.86 (H: 3, 1H, s) ppm, 13C NMR (DMSO-d6):
d 56.6 (C: 4), 115.9 (C: 20), 120.6 (C: 10), 122.5 (C: 8a0), 123.8 (C:
8), 124.1 (C: 5), 124.8 (C: 10), 125.7 (C: 30), 126.5 (C: 40), 126.7 (C:
60), 127.0 (C: 8), 128.0 (C: 9), 128.9 (C: 70), 132.6 (C: 4a0), 132.8
(C: 10a), 133.1 (C: 6a), 140.5 (C: 4a), 143.5 (C: 10b), 149.2 (C:
2) ppm. C22H15NO2 (325.36): calcd. C 81.21, H 4.65, N 4.30; found
C 81.20, H 4.61, N 4.29.
4.3.3. N1-[ -(2-hydroxynaphth-1-yl)naphth-2-yl-methyl]-N2-(4-
a
chlorophenyl)thiourea (13)
Light-yellow crystals: yield 0.342 g (82%), m.p. 193–197 °C. 1H
NMR (DMSO-d6): d 7.26–7.44 (H: 10, 80, 7, 60, 70, 3, 6H, m), 7.50–
7.61 (H: 30, 300, 4, 4H, m), 7.81–7.87 (H: 50, 5, 200, 4H, m), 7.94–
8.03 (H: 8, 6, 2H, m), 8.30 (H: CH, 1H, d, J = 8.6 Hz), 8.36–8.39 (H:
40, 1H, m), 8.65 (H: HCANH, 1H, d, J = 5.7 Hz), 9.96 (H: OH, 1H, s),
10.21 (H: HNC, 1H, s) ppm. 13C NMR (DMSO-d6): d 52.32 (C:
HCANH), 117.7 (C: 1), 118.8 (C: 3), 122.6 (C:8) 123.8 (C: 300, 30),
125.2 (C:6), 125.7 (C: 60, 70), 126.4 (C: 7), 126.7 (C: 80), 127.9 (C:
10), 128.3 (C: 200), 128.4 (C: 40), 128.6 (C: 4), 128.8 (C: 5),,129.5
(C: 8a, 50), 131.2 (C: 4a0), 132.6 (C: 4a0), 132.6 (C: 8a0), 133.6 (C:
400), 136.1 (C: 100), 138.6 (C: 20), 153.8 (C: 2), 179.2 (C: CS) ppm.
C28H21ClN2OS (469.00): calcd. C 71.71, H 4.51, N 5.97; found C
71.69, H 4.49, N 5.93.
4.2.4. 4-(1-Naphthyl)-2,3-dihydro-1H-naphth[2,1-e][1,3]oxazin-2-
one (20)
White crystals, yield 0.38 g (78%), m.p. 234–237 °C. 1H NMR
(DMSO-d6): d 6.70 (H: 4, 1H, s), 6.94 (H: 5, 1H, d, J = 8.5 Hz), 7.48
(H: 20, 1H, d, J = 6.8 Hz), 7.53 (H: 30, 1H, t, J = 7.8 Hz), 7.55–7.575
(H: 6, 60, 80, 3H, m), 7.61 (H: 8, 1H, t, J = 7.6 Hz), 7.68 (H: 9, 1H, t,
J = 7.3 Hz), 7.89 (H: 50, 1H, d, J = 8.1 Hz), 7.95 (H: 40, 1H, d,
J = 7.9 Hz), 8.00–8.02 (H: 70, 1H, m), 8.36 (H: 10, 1H, d, J = 8.3 Hz),
8.33 (H: 7, 1H, d, J = 7.1 Hz), 8.80 (H: 3, 1H, s) ppm. 13C NMR
(DMSO-d6): d 53.7 (C: 4), 116.4 (C: 10), 120.6 (H: 10), 122.5 (C:
5), 123.4 (C: 7), 123.5 (C: 4a), 123.8 (C: 6), 125.8 (C: 80), 126.0 (C:
60), 126.7 (C: 20), 126.9 (C: 8), 127.1 (C: 9, 30), 127.9 (C: 50), 128.9
(C: 40, 70), 130.3 (C: 8a0), 133.2 (C: 6a), 133.9 (C: 10a) ppm.
C22H15NO2 (325.36): calcd. C 81.21, H 4.65, N 4.30; found C
81.20, H 4.64, N 4.32.
4.3.4. N1-[ -(2-hydroxynaphth-1-yl)naphth-1-yl-methyl]-N2-(4-
a
chlorophenyl)thiourea (14)
Light-yellow crystals: yield 0.33 g (80%), m.p. 88–92 °C. 1H NMR
(DMSO-d6): d 12.01–12.27 (H: 3, 4, 5, 80, 60, 7, 70, 40, 200, CH, 11H, m),
12.39 (H: 20, d, J = 8.8 Hz), 12.53 (H: 6, 1H, s), 12.60–12.64 (H: 30, 300,
50, 4H, m), 12.98–13.01 (H: 8, 1H, m), 13.55 (H: NHCH, 1H, d,
J = 8.4 Hz), 14.45 (H: SCNH, 1H, s), 14.63 (H: OH, 1H, s) ppm. 13C
NMR (DMSO-d6): d 56.4 (C: CH), 119.8 (C: 3), 122.1 (C: 8), 123.4
(C: 1), 124.2 (C: 20), 124.7 (C: 6), 125.2 (C: 80), 125.4 (C: 8a0),
125.7 (C: 4,5), 125.8 (C: 60), 126.0 (C: 7), 126.2 (C: 70), 126.4 (C:
40), 127.5 (C: 30), 127.7 (C: 300), 127.9 (C: 50), 128.3 (C: 200), 132.0
(C: 4a), 132.8 (C: 8a), 133.7 (C: 4a0), 138.7 (C: 10), 140.0 (C: 100),
149.6 (C: 400, 2), 180.3 (C: CS) ppm. C28H21ClN2OS (469.00): calcd.
C 71.71, H 4.51, N 5.97; found C 71.68, H 4.49, N 6.00.
4.3. General method for the synthesis of thiourea derivatives (13, 14,
21 and 22)
A mixture of aminonaphthol 4, 5, 9 or 10 (0.30 g, 0.89 mmol)
and 4-chlorophenyl isothiocyanate (0.22 g, 1.29 mmol) in abs. tol-

D. Tóth et al. / Journal of Molecular Structure 929 (2009) 58–66
65
4.4. General method for the synthesis of naphthyl-(4-
chlorophenylimino)naphthoxazine (15, 16, 23 and 24)
124.3 (C: 80), 124.4 (C: 6), 124.8 (C: 400), 125.4 (C: 70), 125.6 (C:
10), 125.8 (C: 60), 126.2 (C: 40), 126.6 (C: 300), 126.7 (C: 300), 127.8
(C: 9, 50), 128.3 (C: 200), 128.6 (20), 130.9 (C: 8a0), 132.9 (C: 4a0),
133.7 (C: 6a), 140.4 (C: 10b), 143.8 (C: 100), 144.8 (C: 2) ppm.
C28H19ClN2O (434.92): calcd. C 77.33, H 4.40, N 6.44; found C
77.35, H 4.37, N 6.42.
To a solution of thiourea 13, 14, 21 or 22 (0.10 g, 0.23 mmol) in
MeOH (6 mL), MeI (0.10 mL, 6.43 mmol) was added and the solu-
tion was stirred for 4 h. After evaporation of the solvent, the resi-
due was stirred in 3 M methanolic KOH (10 mL) for 4 h, after
which the resultant white precipitate was filtered off and recrystal-
lized from n-hexane–iPr2O (5:1, 36 mL).
4.5. General method for the synthesis of naphthylnaphth[1,3]oxazines
(17, 18 and 25)
4.4.1. 1-(2-Naphthyl)-3-(4-chlorophenylimino)-2,3-dihydro-1H-
naphth[1,2-e][1,3]oxazine (15)
Aminonaphthol 4, 5 or 10 (0.15 g, 0.45 mmol), 3 equivalents of
paraformaldehyde, 1.1 equivalent of Et3N and chloroform (8 mL)
were mixed in room temperature for 6 h and the solvent was then
evaporated off. The product was purified by column chromatogra-
phy (silica gel, eluent: n-hexane–EtOAc).
Yellow crystals, yield 0.07 g (76%), m.p. 102–105 °C. 1H NMR
(DMSO-d6): d 6.61 (H: 60, 1H, d, J = 7.0 Hz), 7.13 (H: 1, 1H, s),
7,15–7.23 (H: 300, 70, 3H, m), 7.32–7.45 (H: 5, 10, 50, 30, 4H, m),
7.56–7.64 (H: 8, 200, 2H, m), 7.75–7.82 (H: 10, 80, 2H, m), 7.96–
7.99 (H: 7, 1H, m), 8.06–8.07 (H: 6, 1H, d, J = 9.0 Hz), 7.88–8.89
(H: 9, 1H, d, J = 8.5 Hz), 9.43 (H: 2, 1H, s) ppm. 13C NMR (DMSO-
d6): d 51.3 (C: 1), 114.8 (C: 10a), 116.2 (C: 5), 119.3 (C: 10), 122.9
(C: 30), 123.9 (H: 60), 124.7 (C: 9), 124.8 (C: 40), 124.9 (C: 8a0),
125.5 (C: 70), 126.0 (C: 8), 126.4 (C: 4a0), 127.2 (C: 80), 127.8 (C:
7), 128.2 (C: 300), 128.4 (C: 10a), 128.5 (C: 6a), 128.7 (C: 200),
129.7 (C: 6), 129.8 (C: 10), 130.7 (C: 10b), 130.9 (C: 20), 133.8 (C:
100), 139.6 (C: 400), 144.6 (C: 3), 147.7 (C: 4a) ppm. C28H19ClN2O
(434.92): calcd. C 77.33, H 4.40, N 6.44; found: C 77.30, H 4.42, N
6.48.
4.5.1. 1-(2-Naphthyl)-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazine (17)
Eluent for column chromatography: hexane–EtOAc (4:1), white
crystals, yield 0.067 g (49%), m.p. 157–160 °C. 1H NMR (DMSO-d6):
d 4.35–4.39 (H: 2, 1H, m), 4.60 (H: 3, 1H, dd, J = 10.2, 13.65 Hz),
4.89 (H: 3, 1H, dd, J = 3.8, 9.8 Hz), 5.675 (H: 1, 1H, d, J = 5.0 Hz),
7.14 (H: 1, 1H, d, J = 12.9 Hz), 7.22–7,29 (H: 10, 10, 2H, m), 7.34–
7.36 (H: 5, 1H, m), 7.39–7.41 (H: 9, 10, 2H, m), 7.46 (H: 60, 1H, t,
J = 7.1 Hz), 7.61 (H: 7, 1H, d, J = 8.1 Hz), 7,67 (H: 80, 1H, d,
J = 8.0 Hz), 7.83–7.94 (H: 6, 50, 70, 40, 4H, m) ppm. 13C NMR
(DMSO-d6): d 51.9 (C: 1), 73.2 (C: 3), 114.8 (C: 10b), 119.1 (C: 5),
122.5 (C: 10), 122.9 (C: 8), 125.9 (C: 60), 126.1 (C: 7), 126.4 (C:
9), 127.4 (C: 10), 127.5 (C: 30), 127.6 (C: 40), 127.8 (C: 80), 127.9
(C: 70), 128.3 (C: 6a), 128.5 (C: 50), 128.9 (C: 6), 131.4 (C: 100),
132.2 (C: 4a0), 132.5 (C: 8a0), 140.8 (C: 10a), 152.0 (C:4a) ppm.
C22H17NO (311.38): calcd. C 84.86, H 5.50, N 4.50; found C 84.87,
H 5.49, N 4.51.
4.4.2. 1-(1-Naphthyl)-3-(4-chlorophenylimino)-2,3-dihydro-1H-
naphth[1,2-e][1,3]oxazine (16)
Yellow crystals, yield 0.075 g (82%), m.p. 115–119 °C. 1H NMR
(DMSO-d6): d 7.20 (H: 5, 1H, d, J = 7.6 Hz), 7.32–7.51 (H: 10, 9, 60,
40, 7, 70, 700, 10, 8, 9H, m), 7.61 (H: 200, 2H, d, J = 7.4), 7.70 (H: 20,
1H, s), 7.79–7.84 (H: 300, 50, 6, 3, 4, 6H, m), 8.09 (H: CH, 1H, s),
8.19 (H: NH, 1H, s), 13C NMR (DMSO-d6): d 53.7 (C: 1), 119.7 (C:
10b), 120.3 (C: 5), 123.9 (C: 10), 125.2 (C: 8), 125.9 (C: 200), 126.4
(C: 9), 127.0 (C: 40), 127.6 (C: 60), 128.4 (C: 20), 128.8 (C: 300),
129.1 (C: 6, 7), 129.4 (C: 6a), 130.1 (C: 70), 130.2 (C: 30), 133.3 (C:
8a0, 400), 134.0 (C: 10), 134.1 (C: 10a, 4a0), 139.8 (C: 100), 141.5 (C:
4a), 181.7 (C: 3) ppm. C28H19ClN2O (434.92): calcd. C 77.33, H
4.40, N 6.44; found C 77.31, H 4.38, N 6.48.
4.5.2. 1-(1-Naphthyl)-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazine (18)
Eluent for column chromatography: n-hexane–EtOAc (3:1),
white crystals, yield 0.057 g (42%), m.p. 135–140 °C. 1H NMR
(DMSO-d6): d 4.31–4.34 (H: 2, 1H, m), 4.63 (H: 3, 1H, dd, J =10.4,
13.8 Hz), 4.86 (H: 3, 1H, dd, J = 3.6, 9.8 Hz), 6.33 (H: 1, 1H, d,
J = 4.9 Hz), 6.81 (H: 20, 1H, d, J = 6.7 Hz), 7.08 (H: 10, 1H, d,
J = 8.3 Hz), 7.16–7.25 (H: 50, 5, 30, 9, 4H, m), 7.60 (H: 60, 1H, t,
J = 7.5 Hz), 7.67 (H: 8, 1H, t, J = 7.6 Hz), 7.81–7.84 (H: 40, 6, 80, 3H,
m), 7.98 (H: 70, 1H, d, J = 8.0 Hz), 8.63 (H: 7, 1H, d, J = 8.3 Hz) ppm.
13C NMR (DMSO-d6): d 48.4 (C: 1), 73.2 (C: 3), 114.8 (C: 10b), 119.0
(C: 5), 122.3 (C: 10), 122.9 (C: 9), 124.5 (C: 7), 124.7 (C: 30), 125.8
(C: 8), 126.2 (C: 60), 126.4 (C: 6), 127.4 (C:20), 127.8 (C: 40), 128.3 (C:
6a), 128.5 (C: 80), 128.6 (C: 50), 128.8 (C: 70), 131.0 (C: 8a0), 131.3 (C:
10), 133.9 (C: 4a0), 138.0 (C: 10a), 152.3 (C: 4a) ppm. C22H17NO
(311.38): calcd. C 84.86, H 5.50, N 4.50; found C 84.81, H 5.51, N
4.53.
4.4.3. 4-(2-Naphthyl)-2-(4-chlorophenylimino)-2,3-dihydro-1H-
naphth[2,1-e][1,3]oxazine (23)
Yellow crystals, yield 0.062 g (67%), m.p. 185–188 °C. 1H NMR
(DMSO-d6):
d
6.06 (H: NHACH, 1H, s), 7.19 (H: 40, 1H, d,
J = 8.4 Hz), 7.31 (H: 200, 2H, d, J = 8.8 Hz), 7.43–7.52 (H: 30, 8, 5, 3
H, m), 7.56–7.63 (H: 10, 70, 2H, m), 7.67 (H: 9, 1H, t, J = 7.3 Hz),
7.74(7, 6, 2H, d, J = 8.3 Hz), 7.86–7.93 (H: 300, 50, 80, 10, 5H, m),
8.30 (H: 60, 1H, d, J = 8.3 Hz) ppm. 13C NMR (DMSO-d6): d 57.7 (C:
4), 118.2 (C: 4a), 119.8 (C: 6), 120.6 (C: 60), 122.4 (C: 10a), 123.6
(C: 70), 124.5 (C: 40), 124.9 (C: 10), 125.4 (C: 5), 125.7 (C: 8), 126.0
(C: 30), 126.4 (C: 9). 126.6 (C: 7), 126.8 (C: 10), 127.6 (C: 50),
127.9 (C: 200), 128.5 (C: 300), 128.6 (C: 4a0, 80), 132.3 (C: 6a), 132.9
(C: 8a0, 400) ppm. C28H19ClN2O (434.92): calcd. C 77.33, H 4.40, N
6.44; found C 77.35, H 4.43, N 6.45.
4.5.3. 4-(1-Naphthyl)-2,3-dihydro-1H-naphth[2,1-e][1,3]oxazine (25)
Eluent for column chromatography: hexane–EtOAc (3:1), white
crystals, yield 0.052 g (37%), m.p. 141–145 °C. 1H NMR (DMSO-d6) d
4.34 (H: 3, 1H, ddd, J = 5.4; 6.2, 12.2 Hz), 4.75 (H: 2, 1H, dd,
J = ꢀ10.3, 12.2 Hz), 5.06 (H: 2, 1H, dd, J = 5.4, ꢀ10.0 Hz), 6.03 (H:
4, 1H, d, J = 6.2 Hz), 6.93 (1H, d, J = 7.0 Hz), 6.96 (1H, d,
J = 8.4 Hz), 7.36 (1H, t, J = 7.7 Hz), 7.38 (1H, d, J = 8.5 Hz), 7.59
(4H, m), 7.86 (2H, d, J = 8.8 Hz), 7.98 (1H, d, J = 8.0 Hz), 8.14 (1H,
m), 6.47 (1H, d, J = 8.4 Hz) ppm. 13C NMR (DMSO-d6): d 52.9 (C:
4), 75.3 (C: 2), 117.4 (C: 7), 119.6 (C: 20), 121.4 (C: 60), 123.7 (C:
80), 124.9 (C: 6), 125.3 (C: 10), 125.6 (C: 10), 125.8 (C: 8), 126.3
(C: 70), 126.5 (C: 60), 126.6 (C: 5), 127.6 (C: 30), 128.2 (C: 40),
128.6 (C: 50), 128.9 (C: 9), 129.3 (C: 10a), 131.7 (C: 8a0), 133.6 (C:
6a), 134.2 (C: 4a0), 138.1 (C: 6a), 150.3 (C: 10b) ppm. C22H17NO
(311.38): calcd. C 84.86, H 5.50, N 4.50; found C 84.82, H 5.53, N
4.50.
4.4.4. 4-(1-Naphthyl)-2-(4-chlorophenylimino)-2,3-dihydro-1H-
naphth[2,1-e][1,3]oxazine (24)
Yellow crystals, yield 0.068 g (74%), m.p. 195–196 °C. 1H NMR
(DMSO-d6): d 6.68 (H: 4, 1H, s), 7.03 (H: 80, 1H, d, J = 8.3 Hz), 7.09
(H: 70, 1H, d, J = 15.0 Hz), 7.23 (H: 200, 2H, d, J = 8.4 Hz), 7.41 (H:
60, 1H, t, J = 7.6 Hz), 7.57–7.72 (H: 40, 9, 300, 6, 5, 8, 7H, m), 7.86
(H: 50, 1H, d, J = 8.0 Hz), 7.95 (H: 20, 7, 2H, dd, J = 8.0, 19.8 Hz),
8.33 (H: 30, 1H, d, J = 8.2 Hz), 8.55 (H: 10, 1H, d, J = 8.1 Hz), 9.54
(H: 3, 1H, br) ppm. 13C NMR (DMSO-d6): d 54.3 (C: 4), 117.9 (C:
4a, 10), 119.5 (C: 9), 120.5 (C: 30), 122.4 (C: 10a), 123.5 (C: 5),

66
D. Tóth et al. / Journal of Molecular Structure 929 (2009) 58–66
4.6. General method for the synthesis of naphthyl-(4-nitrophenyl)-2,3-
dihydro-1H-naphth[1,3]oxazines (27, 28, 31 and 32)
149.1 (C: 10b) ppm. C28H20N2O3 (432.47): calcd. C 77.76, H 4.66,
N 6.48; found C 77.78, H 4.64, N 6.50.
Aminonaphthol 4, 5, 9 or 10 (0.15 g, 0.45 mmol), 1 equivalent
amount of 4-nitrobenzaldehyde, 1.1 equivalent of Et3N and meth-
anol (2 mL) were mixed at room temperature for 10 min, and the
resulting crystals were filtered off and recrystallized from iPr2O
(30 mL).
4.6.4. 4-(1-Naphthyl)-2-(4-nitrophenyl)-2,3-dihydro-1H-naphth[2,1-
e][1,3]oxazine (32)
Yellow crystals, yield 0.156 g (80%), m.p. 197–200 °C. 1H NMR
(CDCl3): d 2.87 (H: 3, 1H, s), 5.96 (H: 2, 1H, s), 6.05 (H: 4, 1H, s),
7.02–7.07 (H: 5, 8, 2H, m), 7.32 (H: 30, 1H, t, J = 8.1 Hz), 7.42 (H:
6, 1H, d, J = 8.5 Hz), 7.55–7.61 (H: 60, 8, 9, 3H, m), 7.77 (H: 300, 2H,
J = 8.5 Hz), 8.37 (H: 10, 1H, d, J = 7.5 Hz), 8.48 (H: 20, 1H, d,
J = 8.5 Hz) ppm. 13C NMR (CDCl3): d 53.1 (C: 4), 82.2 (C: 2), 116.6
(C: 4a), 120.2 (C: 6), 121.3 (C: 200), 124.1 (C: 20), 124.8 (C: 30),
125.2 (C: 10a), 125.9 (C: 8, 5), 126.1 (C: 80), 126.5 (C: 60), 126.6
(C: 60), 126.5 (C: 300), 127.7 (C: 70), 127.8 (C: 7), 128.8 (C: 50, 9),
128.9 (C:40) ppm. C28H20N2O3 (432.47): calcd. C 77.76, H 4.66, N
6.48; found C 77.80, H 4.69, N 6.45.
4.6.1. 1-(2-Naphthyl)-3-(4-nitrophenyl)-2,3-dihydro-1H-naphth[1,2-
e][1,3]oxazine (27)
Yellow crystals, yield 0.162 g (84%), m.p. 232–235 °C. 1H NMR
(DMSO-d6): d 4.72 (H: 2, 1H, dd, J = 5.3, 13.9 Hz), 5.82 (H: 3, 1H,
d, J = 13.9 Hz), 6.47 (H: 1, 1H, d, J = 5.2 Hz), 6.93 (H: 30, 1H, d,
J = 7.0 Hz), 7.13 (H: 60, 1H, d, J = 8.3 Hz), 7.22 (H: 10, 1H, t,
J = 6.9 Hz), 7.27–7.31 (H: 5, 70, 2H, m), 7.62 (H: 8, 1H, t,
J = 7.3 Hz), 7.70 (H: 200, 2H, s), 7.72 (H: 9, 1H, s), 7.85–7.92 (H: 80,
50, 6, 3H, m), 8.01 (H: 7, 1H, d, J = 8.1 Hz), 8.22 (H: 80, 1H, d,
J = 8.8 Hz), 8.68 (H: 10, 1H, d, J = 8.5 Hz) ppm. 13C NMR (DMSO-
d6): d 49.9 (C: 1), 81.9 (C: 3), 114.6 (C: 10b), 119.0 (C: 5), 122.6
(C: 60), 123.3 (C: 40), 123.5 (C: 300), 124.4 (C: 10), 124.9 (C: 70),
126.0 (C: 8), 126.5 (C: 9), 126.7(C: 10), 127.8 (C: 30), 127.9 (C: 200),
128.2 (C: 80), 128.6 (C: 7), 128.7 (C: 8a0), 128.8 (C: 50), 129.2 (C:
6), 131.0 (C: 10a), 131.1 (C: 4a0), 134.0 (C: 6a), 137.8 (C: 20),
145.8 (C: 400), 147.4 (C: 100), 152.5 (C: 4a) ppm. C28H20N2O3
(432.47): calcd. C 77.76, H 4.66, N 6.48; found C 77.69, H 4.68, N
6.52.
Acknowledgement
The authors’ thanks are due to the Hungarian Research Founda-
tion (OTKA No. K 75433) for financial support.
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4.6.2. 1-(1-Naphthyl)-3-(4-nitrophenyl)-2,3-dihydro-1H-naphth[1,2-
e][1,3]oxazine (28)
White crystals, yield 0.153 g (80%), m.p. 170–173 °C. 1H NMR
(DMSO-d6): d 4.74 (H: 2, 1H, dd, J = 5.0, 13.6 Hz), 5.76 (H: 3, 1H,
d, J = 13.6 Hz), 5.84 (H: 1, 1H, d, J = 4.9 Hz), 7.29–7.33 (H: 200, 90,
2H, m), 7.4–7.53 (H: 10, 20, 50, 60, 80, 5H, m), 7.69–7.74 (H: 30, 70,
2H, m), 7.80 (H: 300, 2H, d, J = 8.7 Hz), 7.89–7.98 (H: 40, 7, 6, 60,
4H, m), 8.25–8.26 (H: 8, 5, 2H, m). 13C NMR (DMSO-d6): d 54.6
(C: 1), 83.2 (C: 3), 114.6 (C: 10b), 119.1 (C: 5), 123.3 (C: 8), 123.4
(C: 200), 124.0 (C: 20), 124.4 (C: 10), 125.4 (C: 80), 126.0 (C: 60),
126.1 (C: 9), 126.7 (C: 30), 127.5 (C: 40, 70), 127.8 (C: 50), 127.9 (C:
300), 128.1 (C: 6), 128.5 (C: 6a), 128.7 (C: 60), 129.4 (C: 7), 131.3
(C: 8a0), 132.3 (C: 10a), 132.5 (C: 4a0), 140.6 (C: 10), 145.7 (C: 100),
147.2 (C: 400), 152.1 (C:4a) ppm. C28H20N2O3 (432.47): calcd. C
77.76, H 4.66, N 6.48; found C 77.82, H 4.68, N 6.44.
4.6.3. 4-(2-Naphthyl)-2-(4-nitrophenyl)-2,3-dihydro-1H-naphth[2,1-
e][1,3]oxazine (31)
Light-brown crystals, yield 0.151 g (78%), m.p. 190–192 °C. 1H
NMR (CDCl3): d 5.45 (H: 4, 1H, s), 5.92 (H: 2, 1H, d, J = 8.4 Hz),
7.14 (H: 5. 1H, d, J = 8.4 Hz), 7.33–7.36 (H: 60, 1H, m), 7.44–7.51
(H: 10, 5, 2H, m), 7.57–7.59 (10, 9, 7, 3H, m), 7.76–7.83 (H: 80, 70,
2H, m), 7.85–7.87 (H: 200, 2H, d, J = 7.8 Hz), 7.91 (H: 40, 1H, d,
J = 8.5 Hz), 8.01 (H: 50, 1H, d, J = 8.2 Hz), 8.25 (H: 300, 2H, d,
J = 8.7 Hz), 8.32–8.38 (H: 10, 8, 2H, m) ppm. 13C NMR (CDCl3): d
56.0 (C: 4), 82.2 (C: 2), 116.4 (C: 4a), 120.1 (C: 6), 121.3 (C: 8),
123.6 (C: 300), 125.3 (C: 7), 125.9 (C: 60), 126.1 (C: 5),126.3 (C:
10), 126.6 (70), 127.0 (C: 10) 127.5 (C: 200), 127.9 (C: 40), 128.1 (C:
30), 128.5 (C: 80), 128.6 (C: 9), 129.5 (C: 50), 132.9 (C: 4a0), 133.0
(C: 8a0), 133.9 (C: 6a), 140.3 (C: 20), 146.2 (C: 100), 147.9 (C: 400),
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