Synthesis and reactivity of 4-aralkoxy(alkoxy)-5,6-dihydro-2H-1,3-oxazine- 2-ones

Article abstract of DOI:10.1055/s-0029-1217023

The synthesis of previously unreported 4-aralkoxy(alkoxy)-5,6-dihydro-2h-1, 3-oxazine-2-ones, as well as their transformation into various novel 4-functionalized 5,6-dihydro-2h-1,3-oxazine-2-ones and 1,3-oxazinane-2-ones is described. Georg Thieme Verlag

Full text of DOI:10.1055/s-0029-1217023

4068
PAPER
Synthesis and Reactivity of 4-Aralkoxy(alkoxy)-5,6-dihydro-2H-1,3-oxazine-
2-ones
4
-Aralkoxy(alko
h
xy)-5,6-dihy
o
dro-2
H
-1, 3-
m
oxazine-2-ones as Kurz,*a Mehdi Khankischpurb
a
Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf,
Germany
Fax +49(211)8113847; E-mail: Thomas.Kurz@uni-duesseldorf.de
Institute of Pharmacy, University of Hamburg, Bundesstr. 45, 20146 Hamburg, Germany
b
Received 5 June 2009; revised 24 July 2009
dichloromethane at 0 °C, in 30–96% yield (Table 1). The
b-hydroxyimidate hydrochlorides 2 are characterized by
strong C=N absorption bands at 1637–1656 cm–1. Without
further purification, the crude imidate hydrochlorides 2
were converted directly into the corresponding imidate
bases 3 by treatment with a saturated aqueous solution of
potassium carbonate. During the reaction the structures of
imidate bases 3 were determined by IR spectroscopy [IR:
1635–1660 (C=N) cm–1] and TLC. Subsequent cyclic car-
bonylation of imidate bases using CDT [1,1¢-carbonyl-
di(1,2,4-triazole)] as carbonylating agent afforded the
previously unknown 4-aralkoxy(alkoxy)-5,6-dihydro-
2H-1,3-oxazin-2-ones (4a–j) in 55–71% yield, after re-
crystallisation from appropriate solvents (Table 1).
Abstract: The synthesis of previously unreported 4-
aralkoxy(alkoxy)-5,6-dihydro-2H-1,3-oxazine-2-ones, as well as
their transformation into various novel 4-functionalized 5,6-dihy-
dro-2H-1,3-oxazine-2-ones and 1,3-oxazinane-2-ones is described.
Key words: b-hydroxyimidates, cyclization, nitrogen-containing
heterocycles, N-nucleophiles, oxazinanes
The development of simple and efficient methods for the
preparation of new analogs of bioactive heterocyclic com-
pounds represents an important task in organic and medic-
inal chemistry. Among nitrogen–oxygen containing
heterocycles, functionalized 1,3-oxazin(an)es are of inter-
est for organic and medicinal chemists because they are
present in various biologically active compounds and nat-
ural products.1,2 Recently, 1,3-oxazinane-2-ones have at-
tracted considerable interest in medicinal chemistry
especially due to their potent antibacterial activity.3 As
cyclic imides, 1,3-oxazinane-2,4-diones are structurally
related to bioactive heterocycles like glutarimides and
barbiturates. 1,3-Oxazinane-2,4-diones exhibit anti-con-
vulsive, sedative, hypnotic and narcotic properties. 1,3-
Oxazinane-2,4-diones are, for instance, accessible start-
ing from 2,2-disubstituted 3-hydroxycarboxylic acids by
multi-step syntheses.4 The promising biological proper-
ties of the latter heterocycles, as well as their versatile
synthetic applications, prompted us to develop a synthetic
pathway for the preparation of novel 4-functionalized 1,3-
oxazin(an)es.5
+
OH
OH
Cl
NH2
R2OH, HCl
CN
R1
R1
OR2
1
2
O
OH NH
OR2
O
N
K2CO3
CDT
R1
R1
OR2
3
4
Scheme 1 Synthesis of imidates (2) and 4-aralkoxy(alkoxy)-5,6-di-
hydro-2H-1,3-oxazine-2-ones (4)
Heterocycles 4 contain a cyclic carbamate as well as a
semi-cyclic imidate functionality and display two sharp
IR absorption bands at 1718–1727 cm–1 and at 1590–1610
cm–1. The structure of compound 4f was also confirmed
by X-ray structure analysis (Figure 1).7
We now describe the first synthesis of 4-
aralkoxy(alkoxy)-5,6-dihydro-2H-1,3-oxazine-2-ones 4,
as well as their transformation into various novel 4-func-
tionalized 5,6-dihydro-2H-1,3-oxazine-2-ones 5 and 4-
functionalized 1,3-oxazinane-2-ones 6 and 7, by treat-
ment of heterocycles 4 with different nitrogen nucleo-
philes. Our retro-synthetic analysis led to b-
hydroxyimidates as suitable starting materials for the
preparation of the key intermediates 4 (Scheme 1).
Novel b-hydroxyimidate hydrochlorides (2a–j) were syn-
thesized by Pinner reactions of b-hydroxynitriles 1,6 pri-
mary alcohols and hydrogen chloride in anhydrous
SYNTHESIS 2009, No. 23, pp 4068–4074
x
x.
x
x
.
2
0
0
9
Advanced online publication: 23.09.2009
DOI: 10.1055/s-0029-1217023; Art ID: T11609SS
Figure 1 X-ray crystal structure of compound 4f
© Georg Thieme Verlag Stuttgart · New York

PAPER
4-Aralkoxy(alkoxy)-5,6-dihydro-2H-1,3-oxazine-2-ones
4069
Table 1 Imidate Hydrochlorides 2 and 4-Aralkoxy(alkoxy)-5,6-di-
hydro-2H-1,3-oxazine-2-ones 4.
crystal structure of the Z-isomer of compound 6f showed
a semi-cyclic amidoxime functionality in which the
alkoxyimino group is located at carbon atom four of the
1,3-oxazinane-2-one nucleus (Figure 2).7 Semi-cyclic
amidrazones (7a–e) were accessible in 66–87% yield by
Compound R1
R2
Yield (%)
74
2a
2b
2c
2d
2e
2f
Ph
Et
reacting
4-aralkoxy(alkoxy)-5,6-dihydro-2H-1,3-ox-
t-Bu
Me
Et
30
azine-2-ones 4 with N,N-disubstituted hydrazines under
similar reaction conditions (Table 2). According to 1D
and 2D NMR experiments, compounds 7a–e were ob-
tained as mixtures of E- and Z-isomers. In accordance
with amidoximes 6, heterocycles 7 demonstrate a sharp
C=N absorption band at 1648–1656 cm–1, as well as a
strong C=O absorption band at 1726–1734 cm–1.
4-F-C6H4
4-Cl-C6H4
4-Me-C6H4
3-Br-4-F-C6H3
1-Naphthyl
1-Naphthyl
1-Naphthyl
1-Naphthyl
Ph
69
Et
96
Et
66
Et
75
2g
2h
2i
Me
Et
80
R3
O
93
HN
O
O
O
N
R4
Bn
Ph(CH2)2
Et
63
R3
R1
R1
R1
N
2j
86
R4
5
4a
4b
4c
4d
4e
4f
65
O
O
t-Bu
Me
Et
62
H2N OR3
NH
NH
O
N
OR3
4-F-C6H4
4-Cl-C6H4
4-Me-C6H4
3-Br-4-F-C6H3
1-Naphthyl
1-Naphthyl
1-Naphthyl
1-Naphthyl
70
R1
OR2
N
N
4
6
Et
71
R3
O
Et
55
H2N
N
R4
Et
64
R3
N
4g
4h
4i
Me
Et
70
R4
7
67
Scheme 2 Synthesis of 4-amino-5,6-dihydro-2H-1,3-oxazine-2-
ones (5) and 4-functionalized 1,3-oxazinane-2-ones (6 and 7)
Bn
Ph(CH2)2
60
4j
71
The structures of compounds 4–7 were determined by IR,
1H and 13C NMR spectroscopy and by elemental analysis.
Compounds 2–7 were obtained as racemic mixtures.
Next, we investigated the reactivity of the semi-cyclic im-
idate group of compounds 4 towards primary and second-
ary amines, O-substituted hydroxylamines and N,N-
disubstituted hydrazines (Scheme 2). Treatment of 4-
aralkoxy(alkoxy)-5,6-dihydro-2H-1,3-oxazine-2-ones
4
with either primary or secondary amines, furnished the
corresponding 4-amino-5,6-dihydro-2H-1,3-oxazine-2-
ones (5a–f) in 80–87% yield (Table 2). In contrast to imi-
dates 4, heterocycles 5 exhibit sharp C=O absorption
bands at 1663–1687 cm–1. According to H,H-COSY ex-
periments, the heterocyclic amidines 5 contain a 5,6-dihy-
dro-2H-1,3-oxazine-2-one ring system as well as an
exocyclic amino group in ring position four. In addition,
the X-ray crystal structure of compound 5c confirmed the
4-amino-5,6-dihydro-2H-1,3-oxazine-2-one structure.7
Reactions of 4-aralkoxy(alkoxy)-5,6-dihydro-2H-1,3-ox-
azine-2-ones 4 with O-substituted hydroxylamines at
room temperature provided 4-aralkoxy(alkoxy)imino-
1,3-oxazinane-2-ones (6a–f) as Z-isomers in 73–92%
yield (Table 2). In contrast to amidines 5, amidoximes 6
display a sharp C=N absorption band at 1654–1668 cm–1,
which is characteristic for exocyclic aralkoxyimino
groups. In accordance with the spectroscopic data, the
Figure 2 X-ray crystal structure of compound 6f
In conclusion, we have successfully studied the synthesis
of previously unreported 4-aralkoxy(alkoxy)-5,6-dihy-
dro-2H-1,3-oxazine-2-ones 4, as well as their transforma-
tion into various novel 4-functionalized 5,6-dihydro-2H-
Synthesis 2009, No. 23, 4068–4074 © Thieme Stuttgart · New York

4070
T. Kurz, M. Khankischpur
PAPER
IR (KBr): 1646 cm–1.
Table 2 4-Amino-5,6-dihydro-2H-1,3-oxazine-2-ones 5 and 4-
Functionalized 1,3-Oxazinane-2-ones 6 and 7
Ethyl 3-(4-Fluorophenyl)-3-hydroxypropanimidoate Hydro-
chloride (2c)
Colorless crystals (69%); mp 135.2 °C.
IR (KBr): 1637 cm–1.
Entry R1
R3
R4
H
H
H
Yield (%)
86
5a
5b
5c
5d
5e
5f
Ph
PhCH2
t-Bu
2-Cl,6-F-C6H3CH2
2,6-Cl-C6H3CH2
-(CH2)2O(CH2)2-
cyclopentyl
2-Cl-C6H4CH2
PhCH2
84
Ethyl 3-(4-Chlorophenyl)-3-hydroxypropanimidoate Hydro-
chloride (2d)
Colorless solid (96%); mp 123.5 °C.
IR (KBr): 1638 cm–1.
4-Cl-C6H4
4-Me-C6H4
1-Naphthyl
1-Naphthyl
Ph
87
85
H
H
–
80
Ethyl 3-Hydroxy-3-(4-methylphenyl)propanimidoate Hydro-
chloride (2e)
Colorless solid (66%); mp 119.8 °C.
IR (KBr): 1654 cm–1.
82
6a
6b
6c
6d
6e
6f
89
4-Cl-C6H4
4-Me-C6H4
1-Naphthyl
1-Naphthyl
1-Naphthyl
Ph
2-F-C6H4CH2
4-Me-C6H4CH2
PhCH2
–
92
Ethyl 3-(3-Bromo-4-fluorophenyl)-3-hydroxypropanimidoate
Hydrochloride (2f)
Colorless solid (75%); mp 126.4 °C.
IR (KBr): 1637 cm–1.
–
88
–
87
Ph(CH2)3
–
73
Methyl 3-Hydroxy-3-naphthalen-1-ylpropanimidoate Hydro-
chloride (2g)
Colorless solid (80%); mp 211.0 °C.
IR (KBr): 1656 cm–1.
MeO(Me)2C
-(CH2)2NMe(CH2)2-
-(CH2)2O(CH2)2-
Me
–
82
7a
7b
7c
7d
7e
76
4-F-C6H4
1-Naphthyl
1-Naphthyl
1-Naphthyl
75
Ethyl 3-Hydroxy-3-naphthalen-1-ylpropanimidoate Hydro-
chloride (2h)
Colorless solid (93%); mp 112.0 °C.
IR (KBr): 1654 cm–1.
Me
72
-(CH2)5-
66
-(CH2)2O(CH2)2-
87
Benzyl 3-Hydroxy-3-naphthalen-1-ylpropanimidoate Hydro-
1,3-oxazine-2-ones 5 and 4-functionalized 1,3-oxazinane- chloride (2i)
Colorless solid (63%); mp 188.4 °C.
IR (KBr): 1639 cm–1.
2-ones 6 and 7. Currently, we are investigating the biolog-
ical properties and synthetic applications of heterocycles
5–7.
2-Phenylethyl 3-Hydroxy-3-naphthalen-1-ylpropanimidoate
Hydrochloride (2j)
Melting points (uncorrected) were determined on a Mettler FP 62
apparatus. Elemental analyses were carried out with a Heraeus
CHN-O-Rapid instrument. IR spectra were recorded on a Shimadzu
FT-IR 8300. 1H NMR (400 MHz) und 13C NMR (100 MHz) spectra
were recorded on a Bruker AMX 400 spectrometer using TMS as
an internal standard and DMSO-d6 as solvent.
Colorless solid (86%); mp 129.0 °C.
IR (KBr): 1654 cm–1.
Preparation of 4a–j; General Procedure
The crude imidate hydrochlorides 2 (2.5 mmol) were converted into
the corresponding imidate bases by treatment with ice-cold, sat. aq
K2CO3 (40 mL) and subsequent extraction with Et2O (3 × 15 mL).
The organic phase was dried over MgSO4, filtered and the solvent
was removed under reduced pressure. After structure conformation
by IR spectroscopy and TLC, the remaining oil was dissolved in an-
hydrous CH2Cl2 (15 mL). 1,1¢-Carbonyldi-(1,2,4-triazole) (CDT;
451 mg, 2,75 mmol) was added at 5 °C and the reaction mixture was
stirred at r.t. for 1 h. The resulting suspension was washed with H2O
(3 × 10 mL), dried over MgSO4 and filtered. The solvent was re-
moved and the remaining residue was crystallized from Et2O–n-
hexane to afford compounds 4a–j as solid products. Recrystalliza-
tion from EtOAc–n-hexane provided analytically pure products.
Preparation of 2a–j; General Procedure
To a solution of the appropriate b-hydroxynitrile6 1 (15 mmol) in
anhydrous CH2Cl2 (150 mL), HCl gas was added at 0 °C according
to the Pinner synthesis. After 5–7 d at –10 °C, most CH2Cl2 (120
mL) was removed under reduced pressure and anhydrous Et2O
(100–150 mL) was added. The solid imidate hydrochlorides 2a–j
were isolated by filtration, suspended in anhydrous Et2O and fil-
tered. The structures of imidate hydrochlorides 2a–j were con-
firmed by IR spectroscopy. All imidate hydrochlorides were used
for the synthesis of compounds 4 without further purification.
Ethyl 3-Hydroxy-3-phenylpropanimidoate Hydrochloride (2a)
Colorless solid (74%); mp 127.0 °C.
IR (KBr): 1637 cm–1.
4-Ethoxy-6-phenyl-5,6-dihydro-2H-1,3-oxazin-2-one (4a)
Yield: 356 mg (65%); colorless crystals; mp 86.5 °C.
IR (KBr): 1725, 1596 cm–1.
1H NMR (DMSO-d6): d = 1.31 (t, J = 7.2 Hz, 3 H), 2.89 (dd,
J = 16.8, 4.3 Hz, 1 H), 3.01 (dd, J = 16.7, 11.4 Hz, 1 H), 4.38 (q,
Methyl 3-Hydroxy-4,4-dimethylpentanimidoate Hydrochloride
(2b)
Colorless solid (30%); mp 121.0 °C.
Synthesis 2009, No. 23, 4068–4074 © Thieme Stuttgart · New York

PAPER
4-Aralkoxy(alkoxy)-5,6-dihydro-2H-1,3-oxazine-2-ones
4071
J = 7.2 Hz, 2 H), 5.53 (dd, J = 11.5, 4.3 Hz, 1 H), 7.36–7.46 (m,
IR (KBr): 1720, 1591 cm–1.
5 H).
1H NMR (DMSO-d6): d = 1.32 (t, J = 7.1 Hz, 3 H), 2.91 (dd,
J = 16.8, 4.1 Hz, 1 H), 3.05 (dd, J = 16.8, 11.9 Hz, 1 H), 4.39 (q,
J = 7.1 Hz, 2 H), 5.54 (dd, J = 11.8, 3.9 Hz, 1 H), 7.45 (t, J = 8.6
Hz, 1 H), 7.50–7.55 (m, 1 H), 7.83 (dd, J = 6.7, 2.2 Hz, 1 H).
13C NMR (DMSO-d6): d = 13.7, 31.6, 64.1, 73.9, 108.1 (d,
2JC,F = 20.8 Hz), 116.9 (d, 2JC,F = 22.3 Hz), 128.1 (d, 3JC,F = 8.5 Hz),
131.8, 136.0 (d, 4JC,F = 3.1 Hz), 155.3, 158.2 (d, 1JC,F = 245.8 Hz),
178.1.
13C NMR (DMSO-d6): d = 13.7, 31.8, 64.0, 75.1, 126.4, 127.3,
128.6, 137.8, 155.6, 178.2.
Anal. Calcd for C12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found: C,
65.71; H, 6.11; N, 6.53.
6-tert-Butyl-4-methoxy-5,6-dihydro-2H-1,3-oxazin-2-one (4b)
Yield: 282 mg (62%); colorless solid; mp 119.2 °C.
IR (KBr): 1725, 1608 cm–1.
1H NMR (DMSO-d6): d = 0.91 (s, 9 H), 2.49–2.65 (m, 2 H), 3.87 (s,
3 H), 4.09 (dd, J = 12.6, 4.3 Hz, 1 H).
Anal. Calcd for C12H11BrFNO3: C, 45.59; H, 3.51; N, 4.43. Found:
C, 45.55; H, 3.74; N, 4.21.
4-Methoxy-6-naphthalen-1-yl-5,6-dihydro-2H-1,3-oxazin-2-
one (4g)
13C NMR (DMSO-d6): d = 25.2, 26.6, 33.7, 55.4, 81.4, 156.4, 179.8.
Yield: 447 mg (70%); colorless solid; mp 124.0 °C.
IR (KBr): 1727, 1610 cm–1.
Anal. Calcd for C9H15NO3: C, 58.36; H, 8.16; N, 7.56. Found: C,
58.23; H, 8.07; N, 7.44.
1H NMR (DMSO-d6): d = 3.01 (dd, J = 16.7, 4.4 Hz, 1 H), 3.19 (dd,
J = 16.5, 11.8 Hz, 1 H), 3.96 (s, 3 H), 6.37 (dd, J = 11.8, 4.0 Hz,
1 H), 7.55–7.63 (m, 4 H), 7.96–8.01 (m, 2 H), 8.16–8.21 (m, 1 H).
13C NMR (DMSO-d6): d = 31.1, 55.1, 72.3, 123.3, 124.0, 125.3,
126.0, 126.6, 128.7, 129.2, 130.0, 133.0, 133.3, 155.7, 179.0.
4-Ethoxy-6-(4-fluorophenyl)-5,6-dihydro-2H-1,3-oxazin-2-one
(4c)
Yield: 415 mg (70%); colorless crystals; mp 114.4 °C.
IR (KBr): 1721, 1591 cm–1.
1H NMR (DMSO-d6): d = 1.31 (t, J = 7.1 Hz, 3 H), 2.87 (dd,
J = 16.7, 4.2 Hz, 1 H), 3.03 (dd, J = 16.7, 11.8 Hz, 1 H), 4.39 (q,
J = 7.0 Hz, 2 H), 5.53 (dd, J = 12.0, 4.1 Hz, 1 H), 7.24–7.30 (m,
2 H), 7.48–7.53 (m, 1 H).
13C NMR (DMSO-d6): d = 13.7, 31.8, 64.1, 74.6, 115.4 (d,
2JC,F = 21.1 Hz), 128.8 (d, 3JC,F = 8.2 Hz), 134.0 (d, 4JC,F = 2.7 Hz),
162.1 (d, 1JC,F = 245.6 Hz), 178.2.
Anal. Calcd for C15H13NO3: C, 70.58; H, 5.13; N, 5.49. Found: C,
70.36; H, 5.17; N, 5.36.
4-Ethoxy-6-naphthalen-1-yl-5,6-dihydro-2H-1,3-oxazin-2-one
(4h)
Yield: 451 mg (67%); colorless solid; mp 83.0 °C.
IR (KBr): 1720, 1596 cm–1.
1H NMR (DMSO-d6): d = 1.34 (t, J = 7.1 Hz, 3 H), 2.98 (dd,
J = 16.8, 4.1 Hz, 1 H), 3.18 (dd, J = 16.5, 11.7 Hz, 1 H), 4.43 (q,
J = 7.1 Hz, 2 H), 6.37 (dd, J = 11.6, 3.9 Hz, 1 H), 7.55–7.66 (m,
4 H), 7.96–8.02 (m, 2 H), 8.17–8.21 (m, 1 H).
13C NMR (DMSO-d6): d = 13.8, 31.3, 64.1, 72.2, 123.3, 124.0,
125.4, 126.0, 126.7, 128.7, 129.2, 130.1, 133.1, 133.3, 155.9, 178.5.
Anal. Calcd for C12H12FNO3: C, 60.76; H, 5.10; N, 5.90. Found: C,
60.82; H, 5.12; N, 5.81.
6-(4-Chlorophenyl)-4-ethoxy-5,6-dihydro-2H-1,3-oxazin-2-one
(4d)
Yield: 450 mg (71%); colorless crystals; mp 115.5 °C.
IR (KBr): 1721, 1592 cm–1.
Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found: C,
71.20; H, 5.73; N, 5.36.
1H NMR (DMSO-d6): d = 1.31 (t, J = 7.2 Hz, 3 H), 2.90 (dd,
J = 16.7, 4.6 Hz, 1 H), 3.00 (dd, J = 16.7, 11.4 Hz, 1 H), 4.38 (q,
J = 6.6 Hz, 2 H), 5.55 (dd, J = 11.4, 4.3 Hz, 1 H), 7.43–7.57 (m,
4 H).
13C NMR (DMSO-d6): d = 13.7, 31.7, 64.1, 74.4, 128.3, 128.6,
133.3, 136.8, 155.4, 178.0.
4-(Benzyloxy)-6-naphthalen-1-yl-5,6-dihydro-2H-1,3-oxazin-2-
one (4i)
Yield: 497 mg (60%); colorless solid; mp 138.0 °C.
IR (KBr): 1718, 1591 cm–1.
1H NMR (DMSO-d6): d = 3.07 (dd, J = 16.7, 4.0 Hz, 1 H), 3.26 (dd,
J = 16.7, 11.6 Hz, 1 H), 5.40–5.52 (m, 2 H), 6.41 (dd, J = 11.5, 3.9
Hz, 1 H), 7.38–7.46 (m, 3 H), 7.47–7.52 (m, 2 H), 7.55–7.62 (m,
3 H), 7.63–7.67 (m, 1 H), 7.96–8.02 (m, 2 H), 8.20 (d, J = 7.6 Hz,
1 H).
13C NMR (DMSO-d6): d = 40.7, 65.7, 68.4, 123.2, 124.3, 125.7,
126.1, 126.8, 127.7, 128.3, 128.6, 129.4, 130.7, 133.3, 136.1, 137.5,
155.6, 169.6.
Anal. Calcd for C12H12ClNO3: C, 56.82; H, 4.77; N, 5.52. Found: C,
56.56; H, 4.83; N, 5.58.
4-Ethoxy-6-(4-methylphenyl)-5,6-dihydro-2H-1,3-oxazin-2-one
(4e)
Yield: 321 mg (55%); colorless crystals; mp 93.5 °C.
IR (KBr): 1718, 1596 cm–1.
1H NMR (DMSO-d6): d = 1.31 (t, J = 7.1 Hz, 3 H), 2.31 (s, 3 H),
2.84 (dd, J = 16.8, 4.3 Hz, 1 H), 2.99 (dd, J = 16.8, 11.4 Hz, 1 H),
4.37 (q, J = 7.3 Hz, 2 H), 5.47 (dd, J = 11.4, 4.1 Hz, 1 H), 7.23 (d,
J = 7.9 Hz, 2 H), 7.32 (d, J = 8.1 Hz, 2 H).
Anal. Calcd for C21H17NO3: C, 76.21; H, 5.17; N, 4.23. Found: C,
75.93; H, 5.27; N, 3.97.
13C NMR (DMSO-d6): d = 14.1, 21.1, 32.2, 64.4, 75.5, 126.8, 129.5,
135.2, 138.5, 156.1, 178.6.
6-Naphthalen-1-yl-4-(2-phenylethoxy)-5,6-dihydro-2H-1,3-ox-
azin-2-one (4j)
Yield: 613 mg (71%); colorless crystals; mp 123.3 °C.
IR (KBr): 1718, 1590 cm–1.
Anal. Calcd for C13H15NO3: C, 66.94; H, 6.48; N, 6.00. Found: C,
66.95; H, 6.53; N, 5.95.
1H NMR (DMSO-d6): d = 2.99 (dd, J = 16.8, 4.3 Hz, 1 H), 3.06 (t,
J = 6.8 Hz, 2 H), 3.18 (dd, J = 16.8, 11.3 Hz, 1 H), 4.53–4.67 (m,
2 H), 6.36 (dd, J = 11.3, 4.3 Hz, 1 H), 7.21–7.32 (m, 5 H), 7.53–
7.62 (m, 4 H), 7.96–8.02 (m, 2 H), 8.17 (d, J = 7.5 Hz, 1 H).
6-(3-Bromo-4-fluorophenyl)-4-ethoxy-5,6-dihydro-2H-1,3-ox-
azin-2-one (4f)
Yield: 506 mg (64%); colorless crystals; mp 130.5 °C.
Synthesis 2009, No. 23, 4068–4074 © Thieme Stuttgart · New York

4072
T. Kurz, M. Khankischpur
PAPER
13C NMR (DMSO-d6): d = 31.1, 33.9, 68.3, 72.2, 123.3, 124.0,
125.3, 126.0, 126.4, 126.6, 128.4, 128.9, 129.2, 130.1, 132.9, 133.3,
137.6, 155.7, 178.4.
Anal. Calcd for C15H18N2O3: C, 65.68; H, 6.61; N, 10.21. Found: C,
65.39; H, 6.69; N, 10.15.
4-(Cyclopentylamino)-6-naphthalen-1-yl-5,6-dihydro-2H-1,3-
oxazin-2-one (5e)
Yield: 370 mg (80%); colorless solid; mp 133.0 °C.
Anal. Calcd for C22H19NO3: C, 76.50; H, 5.54; N, 4.06. Found: C,
76.63; H, 5.74; N, 4.09.
Preparation of 5a–f, 6a–f and 7a-e; General Procedure
To a solution of the appropriate 4-aralkoxy(alkoxy)-5,6-dihydro-
2H-1,3-oxazine-2-one 4 (1.5 mmol) in anhydrous CH2Cl2 (10 mL),
the appropriate amine, O-substituted hydroxylamine or N,N-disub-
stituted hydrazine (2 mmol) was added at 5 °C. After stirring at r.t.
for 8 h, the solvent was removed and the remaining residue was
crystallized from EtOAc–n-hexane.
IR (KBr): 3226, 1677, 1590 cm–1.
1H NMR (DMSO-d6): d = 1.36–1.46 (m, 1 H), 1.50–1.72 (m, 5 H),
1.84–2.00 (m, 2 H), 2.78–2.93 (m, 2 H), 4.25–4.40 (m, 1 H), 6.14
(dd, J = 10.3, 4.3 Hz, 1 H), 7.52–7.62 (m, 4 H), 7.90–8.02 (m, 2 H),
8.14 (d, J = 7.8 Hz, 1 H), 8.51 (d, J = 6.8 Hz, 1 H).
13C NMR (DMSO-d6): d = 23.9, 23.9, 31.9, 32.3, 52.1, 71.5, 123.6,
123.8, 125.7, 126.3, 126.8, 129.1, 129.1, 130.2, 133.7, 134.8, 157.4.
4-(Benzylamino)-6-phenyl-5,6-dihydro-2H-1,3-oxazin-2-one
(5a)
Yield: 362 mg (86%); colorless crystals; mp 114.5 °C.
Anal. Calcd for C19H20N2O2: C, 74.00; H, 6.54; N, 9.08. Found: C,
73.86; H, 6.79; N, 8.91.
IR (KBr): 3287, 1663, 1591 cm–1.
4-[(2-Chlorobenzyl)amino]-6-naphthalen-1-yl-5,6-dihydro-2H-
1,3-oxazin-2-one (5f)
Yield: 449 mg (82%); colorless crystals; mp 130.5 °C.
IR (KBr): 3227, 1676, 1597 cm–1.
1H NMR (DMSO-d6): d = 2.67–2.89 (m, 2 H), 4.45–4.63 (m, 2 H),
5.39 (dd, J = 9.7, 4.6 Hz, 1 H), 7.22–7.44 (m, 10 H), 8.97 (br s,
1 H).
1H NMR (DMSO-d6): d = 2.97–3.09 (m, 2 H), 4.57 (dd, J = 15.6,
5.0 Hz, 1 H), 4.69 (dd, J = 15.6, 5.5 Hz, 1 H), 6.24 (dd, J = 9.5, 4.5
Hz, 1 H), 7.31–7.37 (m, 3 H), 7.46–7.50 (m, 1 H), 7.53–7.63 (m,
4 H), 7.93–8.02 (m, 2 H), 8.16 (d, J = 8.0 Hz, 1 H), 8.98 (t, J = 5.3
Hz, 1 H).
13C NMR (DMSO-d6): d = 32.5, 43.8, 74.5, 126.6, 127.5, 128.0,
128.7, 128.8, 128.9, 138.0, 139.3, 157.3, 168.7.
Anal. Calcd for C17H16N2O3: C, 72.84; H, 5.75; N, 9.99. Found: C,
72.52; H, 5.84; N, 9.99.
13C NMR (DMSO-d6): d = 31.7, 42.0, 71.7, 123.6, 123.9, 125.7,
126.3, 126.9, 127.7, 129.1, 129.2, 129.5, 129.6, 129.8, 130.2, 132.7,
133.7, 134.6, 135.0, 157.2, 169.2.
6-tert-Butyl-4-[(2-chloro-6-fluorobenzyl)amino]-5,6-dihydro-
2H-1,3-oxazin-2-one (5b)
Yield: 394 mg (84%); colorless crystals; mp 125.7 °C.
IR (KBr): 3226, 1687, 1582 cm–1.
Anal. Calcd for C21H17ClN2O2: C, 69.14; H, 4.70; N, 7.68. Found:
C, 69.43; H, 4.84; N, 7.74.
1H NMR (DMSO-d6): d = 0.89 (s, 9 H), 2.28–2.48 (m, 2 H), 3.86
(dd, J = 12.7, 3.0 Hz, 1 H), 4.52–4.70 (m, 2 H), 7.30 (t, J = 8.6 Hz,
1 H), 7.37–7.50 (m, 2 H), 8.65 (br s, 1 H).
(4Z)-6-Phenyl-1,3-oxazinane-2,4-dione 4-(O-Benzyloxime) (6a)
Yield: 396 mg (89%); colorless solid; mp 188.5 °C.
IR (KBr): 3220, 1718, 1666 cm–1.
1H NMR (DMSO-d6): d = 2.77 (dd, J = 15.7, 3.0 Hz, 1 H), 2.92 (dd,
J = 15.5, 10.7 Hz, 1 H), 4.99 (s, 2 H), 5.58 (dd, J = 10.5, 2.9 Hz,
1 H), 7.28–7.44 (m, 10 H), 10.32 (br s, 1 H).
13C NMR (DMSO-d6): d = 30.0, 74.8, 76.1, 126.2, 127.4, 127.6,
128.1, 128.5, 128.6, 137.7, 138.1, 142.6, 149.4.
13C NMR (DMSO-d6): d = 25.2, 26.2, 33.7, 36.4, 80.3, 115.0, 122.7
2
3
(d, JC,F = 18.3 Hz), 126.0, 131.2, 135.4 (d, JC,F = 6.1 Hz), 157.7,
161.7 (d, 1JC,F = 248.7 Hz), 169.3.
Anal. Calcd for C17H18ClFN2O2: C, 57.60; H, 5.80; N, 8.96. Found:
C, 57.75; H, 5.99; N, 8.93.
6-(4-Chlorophenyl)-4-[(2,6-dichlorobenzyl)amino]-5,6-dihy-
dro-2H-1,3-oxazin-2-one (5c)
Yield: 501 mg (87%); colorless crystals; mp 134.0 °C.
IR (KBr): 3215, 1686, 1576 cm–1.
1H NMR (DMSO-d6): d = 2.67–2.85 (m, 2 H), 4.65–4.79 (m, 2 H),
5.40 (dd, J = 9.7, 4.6 Hz, 1 H), 7.40–7.50 (m, 5 H), 7.52–7.58 (m,
2 H), 8.73 (br s, 1 H).
13C NMR (DMSO-d6): d = 31.9, 41.0, 73.9, 128.7, 128.9, 128.9,
129.0, 131.3, 132.2, 133.4, 136.2, 138.2, 156.8, 168.3.
Anal. Calcd for C17H16N2O3: C, 68.91; H, 5.44; N, 9.45. Found: C,
68.87; H, 5.56; N, 9.22.
(4Z)-6-(4-Chlorophenyl)-1,3-oxazinane-2,4-dione 4-[O-(2-Fluo-
robenzyl)oxime] (6b)
Yield: 481 mg (92%); colorless solid; mp 114.5 °C.
IR (KBr): 3233, 1719, 1668 cm–1.
1H NMR (DMSO-d6): d = 2.75–2.95 (m, 2 H), 5.04 (s, 2 H), 5.61
(dd, J = 10.8, 3.0 Hz, 1 H), 7.15–7.22 (m, 2 H), 7.34–7.40 (m, 1 H),
7.45–7.50 (m, 4 H), 7.52–7.56 (m, 1 H), 10.37 (s, 1 H).
Anal. Calcd for C17H13Cl3N2O2: C, 53.22; H, 3.42; N, 7.30. Found:
C, 53.31; H, 3.43; N, 7.22.
13C NMR (DMSO-d6): d = 29.9, 68.4 (d, J = 3.8 Hz), 75.4, 115.0 (d,
2JC,F = 21.6 Hz), 124.2 (d, 4JC,F = 3.1 Hz), 124.7 (d, 2JC,F = 14.6 Hz),
6-(4-Methylphenyl)-4-morpholin-4-yl-5,6-dihydro-2H-1,3-ox-
azin-2-one (5d)
Yield: 350 mg (85%); colorless crystals; mp 161.7 °C.
3
3
128.2, 128.6, 129.7 (d, JC,F = 8.5 Hz), 130.6 (d, JC,F = 3.8 Hz),
133.3, 136.7, 142.8, 149.2, 160.0 (d, 1JC,F = 245.1 Hz).
IR (KBr): 1686, 1561 cm–1.
Anal. Calcd for C17H14ClFN2O3: C, 58.55; H, 4.05; N, 8.03. Found:
C, 58.55; H, 4.34; N, 7.84.
1H NMR (DMSO-d6): d = 2.31 (s, 3 H), 2.69 (dd, J = 16.4, 11.7 Hz,
1 H), 3.10 (dd, J = 16.4, 3.6 Hz, 1 H), 3.50–3.77 (m, 7 H), 3.91
(ddd, J = 13.1, 5.6, 3.1 Hz, 1 H), 5.22 (dd, J = 11.7, 3.4 Hz, 1 H),
7.22 (d, J = 7.8 Hz, 2 H), 7.32 (d, J = 7.8 Hz, 2 H).
13C NMR (DMSO-d6): d = 20.7, 29.3, 43.7, 46.2, 65.6, 66.0, 73.8,
126.3, 128.9, 136.0, 137.6, 156.8, 168.1.
(4Z)-6-(4-Methylphenyl)-1,3-oxazinane-2,4-dione
4-[O-(4-Methylbenzyl)oxime] (6c)
Yield: 428 mg (88%); colorless solid; mp 173.5 °C.
IR (KBr): 3279, 1719, 1657 cm–1.
Synthesis 2009, No. 23, 4068–4074 © Thieme Stuttgart · New York

PAPER
4-Aralkoxy(alkoxy)-5,6-dihydro-2H-1,3-oxazine-2-ones
4073
1H NMR (DMSO-d6): d = 2.29 (s, 3 H), 2.31 (s, 3 H), 2.71 (dd,
J = 15.6, 3.3 Hz, 1 H), 2.88 (dd, J = 15.7, 10.7 Hz, 1 H), 4.93 (s,
2 H), 5.51 (dd, J = 10.5, 3.0 Hz, 1 H), 7.14 (d, J = 8.0 Hz, 2 H), 7.21
(d, J = 8.0 Hz, 2 H), 7.29 (dd, J = 13.5, 8.0 Hz, 4 H), 10.24 (s, 1 H).
13C NMR (DMSO-d6): d = 20.7, 20.7, 30.0, 74.6, 76.1, 126.2, 127.7,
128.6, 129.0, 134.7, 135.0, 136.6, 138.0, 142.5, 149.5.
1H NMR (DMSO-d6): d (E-isomer) = 2.17 (s, 3 H), 2.33–2.60 (m,
8 H), 2.78 (dd, J = 16.1, 3.0 Hz, 1 H), 2.96 (dd, J = 15.8, 11.0 Hz,
1 H), 5.58 (dd, J = 10.7, 2.4 Hz, 1 H), 7.37–7.48 (m, 5 H), 9.57 (br
s, 1 H); (Z-isomer) = 2.13 (s, 3 H), 2.33–2.60 (m, 8 H), 2.90 (dd,
J = 16.7, 11.2 Hz, 1 H), 3.35 (dd, J = 16.7, 3.1 Hz, 1 H), 5.46 (dd,
J = 11.3, 3.3 Hz, 1 H), 7.37–7.48 (m, 5 H), 10.26 (br s, 1 H).
13C NMR (DMSO-d6): d (E/Z) = 28.3, 32.4, 45.4, 45.5, 53.5, 53.9,
54.0, 54.7, 75.1, 76.1, 126.3, 126.4, 128.5, 128.6, 128.6, 137.7,
138.1, 151.4.
Anal. Calcd for C19H20N2O3: C, 70.35; H, 6.21; N, 8.64. Found: C,
70.23; H, 6.37; N, 8.49.
(4Z)-6-Naphthalen-1-yl-1,3-oxazinane-2,4-dione 4-(O-Benzyl-
oxime) (6d)
Anal. Calcd for C15H20N4O2: C, 62.48; H, 6.99; N, 19.43. Found: C,
62.74; H, 7.26; N, 19.12.
Yield: 452 mg (87%); colorless solid; mp 141.5 °C.
(4E/Z)-6-(4-Fluorophenyl)-4-(morpholin-4-ylimino)-1,3-ox-
azinan-2-one (7b)
Yield: 330 mg (75%); colorless solid; mp 174.5 °C; ratio E/Z =
70:30.
IR (KBr): 3310, 1721, 1662 cm–1.
1H NMR (DMSO-d6): d = 2.89 (dd, J = 15.8, 2.9 Hz, 1 H), 3.10 (dd,
J = 15.7, 10.9 Hz, 1 H), 5.03 (s, 2 H), 6.41 (dd, J = 10.6, 2.5 Hz,
1 H), 7.27–7.33 (m, 1 H), 7.36 (t, J = 7.3 Hz, 2 H), 7.41–7.45 (m,
2 H), 7.52–7.66 (m, 4 H), 7.98 (t, J = 7.1 Hz, 2 H), 8.17 (d, J = 7.8
Hz, 1 H), 10.42 (s, 1 H).
13C NMR (DMSO-d6): d = 29.4, 73.1, 74.8, 123.3, 123.8, 125.3,
126.0, 126.7, 127.4, 127.7, 128.1, 128.7, 129.3, 130.0, 132.9, 133.3,
138.1, 142.8, 149.6.
IR (KBr): 3283, 1726, 1656 cm–1.
1H NMR (DMSO-d6): d (E-isomer) = 2.46–2.64 (m, 4 H), 2.77 (dd,
J = 15.8, 3.0 Hz, 1 H), 2.99 (dd, J = 15.9, 11.2 Hz, 1 H), 3.72 (t,
J = 4.6 Hz, 4 H), 5.60 (dd, J = 11.0, 3.0 Hz, 1 H), 7.23–7.30 (m,
2 H), 7.49–7.56 (m, 2 H), 9.87 (br s, 1 H); (Z-isomer) = 2.46–2.64
(m, 4 H), 2.92 (dd, J = 16.7, 11.4 Hz, 1 H), 3.41 (dd, J = 16.7, 3.1
Hz, 1 H), 3.63 (t, J = 4.1 Hz, 4 H), 5.48 (dd, J = 11.3, 3.0 Hz, 1 H),
7.23–7.30 (m, 2 H), 7.49–7.56 (m, 2 H), 10.41 (br s, 1 H).
Anal. Calcd for C21H18N2O3: C, 72.82; H, 5.24; N, 8.09. Found: C,
72.86; H, 5.37; N, 8.15.
13C NMR (DMSO-d6): d (E/Z) = 28.3, 32.4, 54.7, 55.5, 65.2, 65.4,
6-Naphthalen-1-yl-4-[(3-phenylpropoxy)amino]-5,6-dihydro-
2H-1,3-oxazin-2-one (6e)
Yield: 410 mg (73%); colorless solid; mp 134.5 °C.
IR (KBr): 3229, 1718, 1654 cm–1.
1H NMR (DMSO-d6): d = 1.85–1.96 (m, 2 H), 2.72 (t, J = 7.6 Hz,
2 H), 2.90 (dd, J = 15.7, 2.5 Hz, 1 H), 3.11 (dd, J = 15.7, 11.1 Hz,
1 H), 3.95 (t, J = 6.2 Hz, 2 H), 6.42 (dd, J = 10.7, 2.1 Hz, 1 H),
7.14–7.22 (m, 1 H), 7.22–7.33 (m, 4 H), 7.53–7.64 (m, 3 H), 7.67
(d, J = 7.1 Hz, 1 H), 7.99 (t, J = 7.4 Hz, 2 H), 8.18 (d, J = 7.8 Hz,
1 H), 10.29 (s, 1 H).
2
3
74.5, 75.5, 115.4 (d, JC,F = 21.6 Hz), 128.7 (d, JC,F = 8.5 Hz),
3
4
128.8 (d, JC,F = 8.5 Hz), 133.9 (d, JC,F = 3.1 Hz), 134.3 (d,
4JC,F = 3.1 Hz), 149.4, 149.8, 162.1 (d, 1JC,F = 245.1 Hz).
Anal. Calcd for C14H16FN3O3: C, 57.33; H, 5.50; N, 14.33. Found:
C, 57.24; H, 5.71; N, 14.21.
(4E/Z)-4-(Dimethylhydrazono)-6-naphthalen-1-yl-1,3-ox-
azinan-2-one (7c)
Yield: 316 mg (72%); colorless solid; mp 142.5 °C; ratio E/Z =
68:32.
13C NMR (DMSO-d6): d = 29.5, 30.3, 31.4, 72.3, 73.2, 123.3, 123.8,
125.3, 125.7, 126.0, 126.7, 128.2, 128.4, 128.7, 129.3, 129.9, 133.0,
133.3, 141.9, 142.3, 149.8.
IR (KBr): 3243, 1733, 1645 cm–1.
1H NMR (DMSO-d6): d (E-isomer) = 2.38 (s, 6 H), 2.89 (dd,
J = 15.8, 3.0 Hz, 1 H), 3.11 (dd, J = 15.1, 11.0 Hz, 1 H), 6.37–6.45
(m, 1 H), 7.53–7.69 (m, 4 H), 7.99 (t, J = 8.2 Hz, 2 H), 8.18 (d,
J = 8.0 Hz, 1 H), 9.83 (br s, 1 H); (Z-isomer) = 2.35 (s, 6 H), 3.05
(dd, J = 16.8, 11.0 Hz, 1 H), 3.54 (dd, J = 16.5, 3.3 Hz, 1 H), 6.30
(dd, J = 10.8, 3.0 Hz, 1 H), 7.53–7.69 (m, 4 H), 7.99 (t, J = 8.2 Hz,
2 H), 8.18 (d, J = 8.0 Hz, 1 H), 10.14 (br s, 1 H).
13C NMR (DMSO-d6): d (E/Z) = 27.6, 31.7, 46.8, 47.6, 72.0, 73.9,
123.3, 123.6, 123.8, 125.3, 125.3, 125.9, 126.0, 126.6, 128.7, 129.1,
129.2, 129.9, 130.0, 133.0, 133.3, 133.5.
Anal. Calcd for C23H22N2O3: C, 73.78; H, 5.92; N, 7.48. Found: C,
73.45; H, 6.07; N, 7.45.
4-[(1-Methoxy-1-methylethoxy)amino]-6-naphthalen-1-yl-5,6-
dihydro-2H-1,3-oxazin-2-one (6f)
Yield: 404 mg (82%); colorless solid; mp 175.7 °C.
IR (KBr): 3243, 1735, 1666 cm–1.
1H NMR (DMSO-d6): d = 1.39 (s, 3 H), 1.42 (s, 3 H), 2.96 (dd,
J = 15.8, 2.9 Hz, 1 H), 3.13 (s, 3 H), 3.15 (dd, J = 15.9, 10.6 Hz,
1 H), 6.42 (dd, J = 10.4, 2.6 Hz, 1 H), 7.54–7.65 (m, 3 H), 7.68 (d,
J = 7.1 Hz, 1 H), 7.99 (t, J = 7.2 Hz, 2 H), 8.19 (d, J = 8.1 Hz, 1 H),
10.30 (br s, 1 H).
13C NMR (DMSO-d6): d = 23.5, 23.9, 29.6, 48.4, 73.2, 102.7, 123.4,
123.8, 125.3, 126.0, 126.7, 128.7, 129.3, 130.0, 133.0, 133.3, 143.0,
149.8.
HRFAB-MS: m/z [M + H]+ calcd for C16H18N3O2: 284.1399; found:
284.1389.
Anal. Calcd for C16H17N3O3·0.5H2O: C, 65.74; H, 6.21; N, 14.37.
Found: C, 65.38; H, 6.10; N, 14.27.
(4E/Z)-6-Naphthalen-1-yl-4-(piperidin-1-ylimino)-1,3-ox-
azinan-2-one (7d)
Yield: 320 mg (66%); colorless solid; mp 157.3 °C; ratio E/Z =
63:37.
IR (KBr): 3265, 1730, 1654 cm–1.
1H NMR (DMSO-d6): d (E-isomer) = 1.39 (br s, 2 H), 1.63–1.68 (m,
4 H), 2.51–2.62 (m, 4 H), 2.91 (dd, J = 15.9, 2.9 Hz, 1 H), 3.15 (dd,
J = 15.8, 10.8 Hz, 1 H), 6.42 (dd, J = 10.4, 2.4 Hz, 1 H), 7.55–7.68
(m, 4 H), 7.99 (t, J = 8.2 Hz, 2 H), 8.17–8.22 (m, 1 H), 9.60 (br s,
1 H); (Z-isomer) = 1.31 (br s, 2 H), 1.46–1.55 (m, 4 H), 2.52–2.56
(m, 4 H), 3.06 (dd, J = 16.6, 11.0 Hz, 1 H), 3.52 (dd, J = 16.6, 3.3
Anal. Calcd for C18H20N2O4: C, 65.84; H, 6.14; N, 8.53. Found: C,
65.55; H, 6.20; N, 8.60.
(4E/Z)-4-[(4-Methylpiperazin-1-yl)imino]-6-phenyl-1,3-ox-
azinan-2-one (7a)
Yield: 329 mg (76%); colorless solid; mp 111.0 °C; ratio E/Z =
65:35.
IR (KBr): 3277, 1734, 1648 cm–1.
Synthesis 2009, No. 23, 4068–4074 © Thieme Stuttgart · New York

4074
T. Kurz, M. Khankischpur
PAPER
Hz, 1 H), 6.28 (dd, J = 10.9, 2.9 Hz, 1 H), 7.54–7.67 (m, 4 H), 7.99
(t, J = 8.2 Hz, 2 H), 8.17–8.21 (m, 1 H), 10.38 (br s, 1 H).
13C NMR (DMSO-d6): d (E/Z) = 23.1, 23.4, 24.5, 24.9, 27.6, 31.7,
55.6, 56.4, 72.1, 73.2, 123.3, 123.8, 123.9, 125.3, 125.3, 125.9,
126.0, 126.6, 126.6, 128.7, 129.1, 129.3, 130.0, 132.9, 133.3, 133.6,
149.2, 150.0.
Acknowledgment
The authors thank Prof. Dr. J. Kopf and Miss Isabelle Nevoigt for
their valuable help in the preparation of the X-ray crystal structures.
Moreover, the authors thank Prof. Dr. D. Geffken for his support.
References
Anal. Calcd for C19H21N3O2: C, 70.57; H, 6.55; N, 12.99. Found: C,
70.22; H, 6.74; N, 12.74.
(1) Kupchan, S. M.; Komoda, Y.; Court, W. A.; Thomas, G. J.;
Smith, R. M.; Karim, A.; Gilmore, C. J.; Haltwanger, R. C.;
Bryan, R. F. J. Am. Chem. Soc. 1972, 94, 1354.
(2) (a) Hayes, K. J. Am. Chem. Soc. 1955, 77, 2333.
(b) Bassus, J.; Pacheca, H.; Chareire, M.; Cier, M. Eur. J.
Med. Chem. 1974, 9, 416.
(3) (a) Wang, G.; Ella-Menye, J.-R.; Sharma, V. Bioorg. Med.
Chem. Lett. 2006, 16, 2177. (b) Ella-Menye, J.-R.; Sharma,
V.; Wang, G. J. Org. Chem. 2005, 70, 463. (c) Wang, G.
Anti-Infect. Agents Med. Chem. 2008, 7, 32.
(4E/Z)-4-(Morpholin-4-ylimino)-6-naphthalen-1-yl-1,3-ox-
azinan-2-one (7e)
Yield: 425 mg (87%); colorless solid; mp 187.0 °C; ratio E/Z =
59:41.
IR (KBr): 3267, 1728, 1654 cm–1.
1H NMR (DMSO-d6): d (E-isomer) = 2.61 (t, J = 4.3 Hz, 4 H), 2.92
(dd, J = 15.9, 3.1 Hz, 1 H), 3.16 (dd, J = 16.1, 10.8 Hz, 1 H), 3.75
(t, J = 4.6 Hz, 4 H), 6.43 (dd, J = 10.8, 3.0 Hz, 1 H), 7.54–7.65 (m,
3 H), 7.68 (d, J = 7.0 Hz, 1 H), 7.99 (t, J = 7.9 Hz, 2 H), 8.16–8.23
(m, 1 H), 9.94 (br s, 1 H); (Z-isomer) = 2.54–2.67 (m, 4 H), 3.11
(dd, J = 16.8, 11.3 Hz, 1 H), 3.55–3.60 (m, 1 H), 6.30 (dd, J = 11.0,
3.0 Hz, 1 H), 7.55–7.69 (m, 4 H), 7.99 (t, J = 7.9 Hz, 2 H), 8.16–
8.23 (m, 1 H), 10.50 (br s, 1 H).
13C NMR (DMSO-d6): d (E/Z) = 27.7, 31.8, 54.3, 54.8, 55.6, 65.2,
65.4, 65.7, 72.2, 73.1, 123.3, 123.4, 123.8, 124.1, 125.3, 125.3,
126.0, 126.6, 126.7, 128.7, 129.2, 129.3, 130.0, 132.9, 133.3, 133.4,
149.7, 150.0, 155.7.
(4) Testa, E.; Fontanella, L.; Cristiani, G.; Gallo, G. J. Org.
Chem. 1959, 24, 1028.
(5) Church, T. L.; Byrne, C. M.; Lobkoovsky, E. B.; Coates, G.
W. J. Am. Chem. Soc. 2007, 129, 8156.
(6) Kaiser, E. M.; Hauser, C. R. J. Org. Chem. 1968, 33, 3402.
(7) Crystallographic data for compounds 4f, 5c and 6f have been
deposited with the Cambridge Crystallographic Data Centre
as supplementary publication numbers CCDC 726927 (4f),
CCDC 726928 (5c) and CCDC 726929 (6f).
Anal. Calcd for C18H19N3O3: C, 66.45; H, 5.89; N, 12.91. Found: C,
66.52; H, 6.10; N, 12.76.
Synthesis 2009, No. 23, 4068–4074 © Thieme Stuttgart · New York