Transformation of furan-2,3-diones with 1,8-diaminonaphthalene to naphtho-[1,8-ef][1,4]diazepin-2(1H)-ones

Article abstract of DOI:10.1080/00397910902796094

Naphtho[1,8-ef][1,4]diazepin-2(1H)-ones were obtained from furan-2,3-diones with 1,8-diaminonaphthalene.

Full text of DOI:10.1080/00397910902796094

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Transformation of
Furan-2,3-diones with
1,8-Diaminonaphthalene
to Naphtho-[1,8-ef]
[1,4]diazepin-2(1H)-ones
Şevket Hakan Üngören a
a Department of Chemistry, Faculty of Art and
Sciences, Bozok University, Yozgat, Turkey
Version of record first published: 08 Sep 2009.
To cite this article: Şevket Hakan Üngören (2009): Transformation of Furan-2,3-diones
with 1,8-Diaminonaphthalene to Naphtho-[1,8-ef][1,4]diazepin-2(1H)-ones, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:20, 3657-3662
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Synthetic Communications1, 39: 3657–3662, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902796094
Transformation of Furan-2,3-diones with
1,8-Diaminonaphthalene to Naphtho-
[1,8-ef][1,4]diazepin-2(1H)-ones
¨
¨
S¸evket Hakan Ungoren
Department of Chemistry, Faculty of Art and Sciences,
Bozok University, Yozgat, Turkey
Abstract: Naphtho[1,8-ef][1,4]diazepin-2(1H)-ones were obtained from furan-2,3-
diones with 1,8-diaminonaphthalene.
Keywords: 1,8-Diaminonaphthalene, 2,3-furandiones, naphtho[1,4]diazepines,
1,2,4-triones
INTRODUCTION
Naturally occuring or synthetic heterocyclic amino acid derivatives con-
stitute an important resource for new drugs. For instance, derivatives of
pyrrole,[1] isoxazole,[2] tetrazole,[3] and pyrazole[4] containing an amino
acid=amide moiety have been reported as bioactive materials. Among
these types of heterocycles, 1,4-benzodiazepines (like diazepam) are ther-
apeutically used as drugs acting on the central nervous system (CNS).[5]
The clinical importance of 1,4-benzodiazepines has led to extensive syn-
thetic studies on 1,4-benzodiazepines fused heterocycles.
Just like benzodiazepines and its related heterocyclic compounds,
naphtho[1,4]diazepine derivatives might also exhibit psychotherapeutic
effects with a functional 1,4-arodiazepine ring. Therefore, we have stu-
died the synthesis of novel naphtho[1,4]diazepines containing an a-amino
Received December 17, 2008.
Address correspondence to S¸evket Hakan Ungo¨ren, Department of
¨
Chemistry, Faculty of Art and Sciences, Bozok University, 66200 Yozgat,
Turkey. E-mail: hungoren@erciyes.edu.tr
3657

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S¸. H. Ungoren
3658
acid moiety. Our approach was to react 1,8-diaminonaphthalene with
both furan-2,3-diones and 1,2,4-triketones to yield naphtho[1,8-ef][1,4]
diazepin-2(1H)-ones.
RESULTS AND DISCUSSION
Naphtho[1,8-ef][1,4]diazepin-2(1H)-ones 3 were readily obtained by
cyclocondensation of 2,3-furandiones (1a–d) with 1,8-diaminonaphtha-
lene (2) (72–83%). When the reaction of 1 and 2 was carried out at room
temperature in benzene, compounds 3a–d precipitated as pure crude
products, and additional purifications were redundant. However, when
the reactions of 1a–d and 2 were conducted at high temperatures in
solvents, no isolable products were obtained.
Formation of 3a–d is thought to proceed via a sequence as outlined
in Scheme 1. The reaction is started by nucleophilic attack of the amino
group of 1,8-diaminonaphthalene on the carbonyl group at position 3 of
furan-2,3-dione, forming a Schiff base, which was not isolated. Through
attack of a second amino group on the lactone carbonyl group, ring
opening occurs, and naphthodiazepin rings are formed simultaneously.
The NH and OH proton signals of compounds 3a–d were detected
between 8.49–9.20 and 5.60–6.55 ppm as broad bands, respectively.
Although aryl0 C¼O was not observed in the 13C NMR spectra, the acet-
yl0 C¼O of 3a–d were found between 193.68 and 194.30 ppm. In the infra-
red (IR) spectra, the C¼O absorptions of 3a at 1710 (acetyl), 1644 cmꢀ1
(ring), and C¼N absorption at 1635 cmꢀ1 were detected.
There was no indication of the tautomeric forms of 3a–d, both by
their IR spectra in the solid state and by their NMR spectra in CDCl3
solution, and they exist exclusively in the enolic form.
On the other hand, direct reactions of 1,2,4-triones (4a, b) with 2
produced ethyl 1H-perimidine-2-carboxylate instead of naphtho[1,8-
ef][1,4]diazepin-2(1H)-ones (5). Synthesis of ethyl 1H-perimidine-2-
carboxylate was previously reported from the reaction of 2 with diethyl
oxalate.[6] In addition, hydrolysis of compound 3 with ammonia solution
did not give an isolable product of compound 5 (Scheme 1).
EXPERIMENTAL
1a–d were prepared according to published method.[8,6] Melting points
were determined on an Electrothermal 9200 apparatus and are
uncorrected. Elemental analyses were carried out using a LECO-932
CHNSO analyzer. IR spectra were recorded on a Jasco Plus model 460

Naphtho[1,8-ef][1,4]diazepin-2(1H)-ones
3659
Scheme 1. Reactions of 1,8-diaminonaphthalene with 2,3-furandiones and
1,2,4-triones.
1
Fourier transform (FT–IR) spectrometer as KBr pellets. H (400-MHz)
and 13C NMR (100-MHz) spectra were obtained on a Bruker Avance
DPX-400 spectrometer in CDCl3. The chemical shifts are reported in
parts per million (ppm) from tetra methyl silane (TMS) and are given
in d units. All experiments were followed by thin-layer chromatography
(TLC) using DC Alufolien Kieselgel 60 F 254 Merc and Camag TLC
lamb (254=366 nm).
General Procedure for 3
A solution of furan-2,3-diones (1a–d) (1 mmol) in dry benzene (30 ml) and
2 (0.158 g, 1 mmol) were stired for 24 h. After solvents were removed by

¨
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S¸. H. Ungoren
3660
filtration, the crude products (3a–d) were washed with benzene and
diethyl ether.
3-(1-Acetyl-2-hydroxy-1-propen-1-yl)naphtho[1,8-ef][1,4]diazepin-
2(1H)-one (3a)
Compound 3a was prepared from 0.154 g 1a and 0.158 g 2. Oranꢀge1
crystals. Yield 0.245 g (83%); mp 143ꢁC. IR (KBr): n ¼ 3332 cm
(N-H), 3297 (O-H, br.), 1710 (MeC¼O), 1664 (C¼O, ring), 1635
1
(C¼N). H NMR (400 MHz, CDCl3): d ¼ 1.63 (s, 3H, C¼CꢀCH3), 2.68
(s, 3H, COCH3), 5.60 (s, 1H, broad OH), 6.78–8.03 (m, 6H, Ar-H),
8.64 ppm (s, 1H, broad NH). 13C NMR (CDCl3) d ¼ 23.37 (CH3ꢀ
C¼CꢀOH), 30.57 (CH3C¼O), 109.84, 114.68, 115.24, 118.58, 121.20,
125.20, 126.23, 127.59, 127.94, 128.32, 134.09, 137.65 (arom. and aliph.
C¼C and C¼N), 161.76 (NHC¼O), 194.30 (MeC¼O). C17H14N2O3
(294): calcd. C, 69.38; N, 9.52; H, 4.79; found C, 69.19; N, 9.64; H, 4.73.
3-[1-Acetyl-2-hydroxy-2-(4-methoxyphenyl)vinyl]naphtho[1,8-ef]
[1,4]diazepin-2(1H)-one (3b)
Compound 3b was prepared from 0.246 g 1b and 0.158 g 2. Orange cryꢀs1-
tals. Yield 0.306 g (79%); mp 210ꢁC. IR (KBr): n ¼ 3433 (O-H, br) cm
,
1
3332 (N-H), 1710 (MeC¼O), 1664 (C¼O, ring), 1635 (C¼N). H NMR
(400 MHz, CDCl3): d ¼ 2.50 (s, 3H, COCH3), 3.66 (s, 3H, OCH3), 6.48
(s, 1H, broad OH), 6.65–7.97 (m, 10H, Ar-H), 9.20 ppm (s, 1H, broad
NH). 13C NMR (CDCl3) d ¼ 30.05 (CH3C¼O), 55.07 (OCH3), 110.14,
113.85, 115.41, 115.73, 118.99, 122.01, 125.28, 126.19, 127.49, 128.86,
128.32, 129.49, 134.04, 137.89, 159.28 (arom. and aliph. C¼C and
C¼N), 162.57 (NHC¼O), 193.69 (MeC¼O). C23H18N2O4 (386): calcd.
C, 71.49; N, 7.25; H, 4.70; found C, 71.56; N, 7.14; H, 4.78.
3-[1-Acetyl-2-(3,4-dimethoxyphenyl)-2-hydroxyvinyl]naphtho[1,8-ef]
[1,4]diazepin-2(1H)-one (3c)
Compound 3c was prepared from 0.276 g 1c and 0.158 g 2. Orange
crystals. Yield 0.308 g (74%); mp 198ꢁC. IR (KBr): n ¼ 3434 (O-H, br.)
1
cmꢀ1, 3350 (N-H), 1708 (MeC¼O), 1656 (C¼O, ring), 1624 (C¼N). H
NMR (400 MHz, CDCl3): d ¼ 1.63 (s, 3H, C¼C-CH3), 2.68 (s, 3H,
COCH3), 5.60 (s, 1H, broad OH), 6.78–8.03 (m, 6H, Ar-H), 8.49 ppm
(s, 1H, broad NH). 13C NMR (CDCl3) d ¼ 29.90 (CH3C¼O), 55.67,
55.89 (OCH3), 110.01, 110.13, 110.89, 115.39, 119.21, 119.42, 121.75,

Naphtho[1,8-ef][1,4]diazepin-2(1H)-ones
3661
125.32, 126.26, 127.47, 128.40, 130.09, 134.09, 137.89, 148.68, 148.86
(arom. and aliph. C¼C and C¼N), 162.58 (NHC¼O), 193.68 (MeC¼O).
C24H20N2O5 (416): calcd. C, 69.22; N, 6.73; H, 4.84; found C, 69.07; N,
6.68; H, 4.84.
3-[1-Acetyl-2-hydroxy-2-(2-naphthyl)vinyl]naphtho[1,8-ef][1,4]-
diazepin-2(1H)-one (3d)
Compound 3d was prepared from 0.266 g 1d and 0.158 g 2. Orange
crystals. Yield (0.292 g, 72%); mp 231ꢁC. IR (KBr): n ¼ 3385 (O-H, br.)
cmꢀ1, 3347 (N-H), 1710 (MeC¼O), 1659 (C¼O, ring), 1638 (C¼N).
1H NMR (400 MHz, CDCl3): d ¼ 2.48 (s, 3H, COCH3), 6.55 (s, 1H,
broad OH), 7.20–8.05 (m, 6H, Ar-H), 9.18 ppm (s, 1H, broad NH). 13C
NMR (CDCl3) d ¼ 30.00 (CH3C¼O), 110.06, 115.44, 119.18, 121.78,
123.49, 125.38, 126.19, 126.21, 126.55, 126.89, 127.32, 127.56, 128.24,
128.55, 132.75, 134.03, 135.11, 137.97 (arom. and aliph. C¼C and
C¼N), 162.50 (NHC¼O), 193.62 (MeC¼O). C26H18N2O3 (406): calcd.
C, 76.83; N, 6.89; H, 4.46; found C, 76.71; N, 6.80; H, 4.49.
Ethyl 1H-Perimidine-2-carboxylate
A mixture of powdered 2 (0.158 g, 1 mmol) and 4b (0.250 g, 1 mmol) or 4c
(0.280 g, 1 mmol) were heated at 90ꢁC for 1 h in a tube. Residue was
recrystallized from dry xylene to give ethyl 1H-perimidine-2-carboxylate
as scarlet powders. Yield (56% from 4b, 65% from 4c); mp 199–201ꢁC
(lit.[8] mp 200.5–202.5ꢁC).
ACKNOWLEDGMENT
The author is very grateful to Bozok University Research Fund for finan-
cial support.
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