Investigation of interaction of benzoquinones and naphthoquinones with substituted hydrazides

Article abstract of DOI:10.1002/jhet.278

(Chemical Equation Presented) Nucleophilic attack by substituted hydrazides on C-2, C-3 of 2,3,5,6-tetrachloro-1,4-benzoquinone and 2,3-dichloro-1,4- naphthoquinone initiates the formation of benzo[e][1,3,4]oxadiazine and benzo- as well as naphthoxadiazepine derivatives. On the other hand, substituted hydrazides attack 1,4-naphthoquinone-2,3-dicarbonitrile to form benzo[f]indazole-4,9-dione derivatives. A rationale for the conversions observed is presented.

Full text of DOI:10.1002/jhet.278

118
Investigation of Interaction of Benzoquinones and
Naphthoquinones with Substituted Hydrazides
Vol 47
Alaa A. Hassan,* Yusria R. Ibrahim, and Ahmed M. Shawky
Department of Chemistry, Faculty of Science, Minia University, El-Minia, A. R. Egypt
*E-mail: alaahassan2001@yahoo.com
Received March 20, 2009
DOI 10.1002/jhet.278
Published online 5 January 2010 in Wiley InterScience (www.interscience.wiley.com).
Nucleophilic attack by substituted hydrazides on C-2, C-3 of 2,3,5,6-tetrachloro-1,4-benzoquinone
and 2,3-dichloro-1,4-naphthoquinone initiates the formation of benzo[e][1,3,4]oxadiazine and benzo- as
well as naphthoxadiazepine derivatives. On the other hand, substituted hydrazides attack 1,4-naphthoqui-
none-2,3-dicarbonitrile to form benzo[f]indazole-4,9-dione derivatives. A rationale for the conversions
observed is presented.
J. Heterocyclic Chem., 47, 118 (2010).
INTRODUCTION
2,3,5,6-tetrachloro-1,4-benzoquinone (2), 2,3-dichloro-
1,4-naphthoquinone (3) and 1,4-naphthoquinone-2,3-
dicarbonitrile (4).
2,3,5,6-Tetrachloro-1,4-benzoquinone (2) and 2,3-
dichloro-1,4-naphthoquinone (3) undergo nucleophilic
substitution of one or two chlorine atoms by primary
amines [1,2], amino acids [3,4], and aziridines [5]. Up to
four nitrogen residues are introduced into 2 and 3 in their
reaction with pyrazole [6], imidazole [7,8], and 1,2,4-tria-
zole [7,9]. Amides and thioamides were added to 3 to
produce two related heterocyclic diones series in excel-
lent yields [10–14]. The reaction of 2 and 3 with N1, N2-
diarylamidines to give benzimidazole and indole deriva-
tives has been reported [15,16]. Heterocyclization of sub-
stituted thiosemicarbazides and dithiobiureas during the
reaction with benzoquinones and naphthoquinones, dif-
ferent successful approach for the synthesis of oxathia-
diazole [17], thiadiazine [17,18], imidazoxadiazole [19],
imidazothiadiazole [20], and indazole [21] derivatives. A
large variety of quinones, including many fused heterocy-
clic rings, have been used as synthetic intermediates in
medicinal [22–25] and dye chemistry [26–29].
Equimolar solutions of 1a-e and 2 in DMF upon
standing for 48 hours at room temperature formed the
derivatives of benzoxadiazepine 5a-e as major product
(66–74%) and benzoxadiazine 6a-e as minor product
(17–22%) (Scheme 1).
The structural assignment of 6,8,9-trichloro-7-
hydroxy-2-(substituted)benzo[f][1,3,4]oxadiazepine-5(H)-
one 5a-e are based on the following spectral data: The IR
spectrum showed a broad bands at mmax 3455–3480 and
3280–3335 because of OH and NH, sharp band at 1700–
1710 for carbonyl group and 1620–1630 cmꢀ1 for C¼¼N.
The 1H NMR displayed two broad singlets, one at
d ¼ 7.79–7.86 ppm and the other at d ¼ 9.57–9.62 ppm
because of oxadiazepine-NH and phenolic-OH, respec-
tively. The 13C NMR spectrum showed a signal at d ¼
152.46–152.75 ppm for aromatic quaternary carbon
atom bearing a hydroxyl group [30], the presence of one
carbonyl group at d ¼ 169.73–169.84 ppm and oxadia-
zepinone-C-2 at d ¼ 156.66–156.86 ppm. In the 13C
NMR the absence of characteristic resonance signals of
the carbonyl carbon atoms of chloranil 2 around 182–
184 [31] ppm support the structure 5a-e. The formation
of 5b was further confirmed by mass spectrometry.
RESULTS AND DISCUSSION
We report herein the results of our recent investiga-
tion on the reactions of substituted hydrazides 1a-e with
C
V
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Investigation of Interaction of Benzoquinones and Naphthoquinones with
Substituted Hydrazides
119
Scheme 1
hydrazino-1,2,4-triazinoindole [32], amino- and dia-
mino-1,2,4-triazole derivatives [9] and 3,5-diaminopyra-
zoles [6] with chloronated benzoquinones and
naphthoquinones.
Unstable charge-transfer complexes may be formed
during the reaction between chlorinated quinone and
DMF, followed by the formation of anionic cationic rad-
icals 7. Recombination of the radicals afforded the
adduct 8, which gradually split off a molecule of hydro-
gen chloride to form 9. The latter interacted with the hy-
drazide 1 with elimination a molecule of dimethylamine
and another of water in presence of hydrogen protons
(possibly from 1) to afford benzoxadiazepine derivatives
5a-e. On the other hand compound 9 reacted with 1 to
give 6a-e as illustrated in Scheme 2.
Scheme 2
Besides the molecular ion at 362/368, the characteristic
fragment ion patterns of trichloro compounds were
observed. The EI mass spectrum of 5b is characterized
by loss of 111 a.m.u (most likely thiophene carbonyl
group) followed by loss of 28 a.m.u (dinitrogen or car-
bonyl group). The a priori possible isomeric structure
12a-e (Scheme 2) was ruled out on the basis of IR and
13C NMR spectral data.
The structural assignment of 6a-e was supported by
the following spectral data: In its 13C NMR spectrum,
the characteristic absorption signal of two carbonyl car-
bon atoms of chloranil are replaced by signals at d ¼
140.87–141.12 and d¼152.46–153.04 ppm, which are
characteristic of aromatic quaternary carbon bearing ox-
ygen [30]. In addition PhACACl appears at 121.94–
122.32 and 123.14–123.46 [31] ppm. The carbonyl
group attached to N(CH3)2 resonates at d ¼ 171.23–
171.42 [31] ppm. The IR spectrum of 6a-e showed
bands at 3470–3490 and 3290–3315 due to OH and NH,
and strong absorption at 1680–1690 due to carbonyl
1
group. The H NMR spectrum of 6a-e showed signals at
3.36–344, 7.69–7.81, and 9.61–9.74 due to N(CH3)2,
oxadiazine–NH and hydroxyl group, respectively. It is
worthy to note that the mass spectra of compounds 6a-e
show the loss of O¼¼CAN(CH3)2, N2 or CO, as well as
RCO from the molecular ions.
Scheme 2 summarizes the reactions responsible for
the formation of compounds 5 and 6. It shows the inter-
action of 1a-e with chloranil (2) in DMF as a solvent
proceeded in an interesting manner because of the par-
ticipation of DMF in the course of the reaction, as
reported in our earlier publications on the reactions of
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A. A. Hassan, Y. R. Ibrahim, and A. M. Shawky
Vol 47
Scheme 4
2,3-Dichloro-1,4-naphthoquinone 3 was chosen to
compare its reactivity toward the hydrazides 1a-e with
chloranil (2).
It has been described in the literature that 3 resembles
2 in most of its substitution reactions, especially with
compounds containing nucleophilic nitrogen (amines,
amino acids, pyrazoles, imidazoles, etc) [1–7,9]. From
this point of view one might expect that 1a-e should
react with 2 similarly like 3. Earlier, it had been
reported that 1a reacted with 3, ultimately giving 2,3-
di(benzoyl-hydrazinyl)naphthalene-1,4-dione (14) (Sch-
eme 3). We report here the results of recent investiga-
tions on the reaction of 1a-e with 3.
Mixing equimolar amounts of 1a-e and 3 in DMF for
72 hours led to the formation of 2-substituted naph-
tho[2,3-f][1,3,4]oxadiazepine-5,6,11-(4H)-triones 16a-e
(Scheme 3). The IR spectra of 16a-e (in KBr) showed
NH absorption at 3230–3245 cmꢀ1, carbonyl groups at
1705–1725 and 1680–1690, as well as bands characteris-
tic of CAOAC and C¼¼N at 1090 and 1620–1630,
respectively. The 1H NMR spectra of 16a-e clearly
show one broad signal at 7.78–7.84 ppm due to oxadia-
zepine-NH.
naphthoquinone-2,3-dicarbonitrile (4). Substituted ben-
zo[f]indazolediones 17a-e and diacylhydrazines 18a-e
were obtained from the reaction of 1a-e with (4)
(Scheme 4).
Compounds 17a-e exhibited IR absorptions at 3330–
1
3345 (NH2), 1685–1690 and 1660–1665 (CO). The H
NMR spectra of 17a-e clearly showed one broad signal
at 6.67–6.73 ppm because of NH2, besides the aromatic
protons. Signals at 153.29–153.48 (C-3), 100.89–101.46
(C-3a), 139.81–140.11 (C9a), 188.54–188.74 (C-4),
187.75–187.89 (C-9), 165.46–165.73 (CO), 137.86
(indole-C-2) and 99.74 (indole-C-5) in the 13C NMR
spectra of 17a-e lend further supported the structure
assigned to 17a-e. The structure of 17e was evidently
confirmed by mass spectrometrically, besides the molec-
ular ion at m/z ¼ 356 (39%), the characteristic fragment
ion pattern of indole-2-carbonyl at 144 (86), C6H4COþ
group at 104 (77), benzoyl cation at 91 (89) and 77
(100) as a base peak. A possible reaction process is
depicted in Scheme 5.
Signals around 169.58–169–84 (C-5), 187.39–187.78
(C–6) [31] and 187.33–187.80 (C-11) [31] and 156.78–
156.86 (C-2), in 13C NMR spectra lend further support
to the structure assigned to 16a-e. The EI-mass spectra
need a brief comment for 16a-e, m/z ¼ 213 represent
the derivative of benzindazolyl fragment formed by
release of corresponding RCO from the molecular ion,
which undergo loss of 28 a.m.u (dinitrogen or CO
group).
The present investigation also dealt with the study of
the chemical behavior of hydrazides 1a-e toward 1,4-
Scheme 3
Scheme 5
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Investigation of Interaction of Benzoquinones and Naphthoquinones with
Substituted Hydrazides
121
removed and extracted. The fastest migrating one contained
substituted benzo[1,3,4]oxadiazepine 5a-e, the slowest migrat-
ing zone contained substituted benzo-[1,3,4]oxadiazinecarboxa-
mide 6a-e. Extraction of zones with acetone and recrystallized.
6,8,9-Trichloro-7-hydroxy-2-phenylbenzo[f][1,3,4]-oxadia-
zepin-5-(4H)-one (5a). Compound 5a was obtained as reddish
brown crystals (0.264 g, 74%), mp 216–217ꢁC (acetonitrile),
IR: 3460 (OH), 3310 (NH), 1705 (CO), 1625 (C¼¼N), 1596
(ArAC¼¼C), 1085 (CAOAC). 1H NMR: d 7.18–7.53 (m, 5H,
ArAH), 7.84 (br, 1H, oxadiazepineANH), 9.56 (br, 1H, OH);
13C NMR: d 120.71 (C-5a), 122.53, 123.74, 124.17 (C-6, 8
and 9), 126.51, 128.26, 130.14 (ArACH), 134.72 (ArAC),
147.38 (C-9a), 152.56 (C-7), 156.86 (C-2), 169.84 (CO); ms
m/z: 356/362 (Mþ, 42), 322 (26), 286 (34), 250 (21), 194 (26),
158 (11), 105 (67), 77 (100), 65 (49); Anal. Calcd. for
C14H7Cl3N2O3 (357.58): C, 47.02; H, 1.97; Cl, 29.74; N, 7.83.
Found: C, 46.81; H, 2.11; Cl, 29.51; N, 7.64.
CONCLUSIONS
In a fairly complex and multistep process, ben-
zo[e][1,3,4]oxadiazine, benzo[f]indazole-4,9-dione and
benzoxadiazepine as well as naphthoxadiazepine deriva-
tives are formed from 1a-e and (2-4) during the nucleo-
philic attack by substituted hydrazides on C-2, C-3 of
2,3,5,6-tetrachloro-1,4-benzoquinone and 2,3-dichloro-
1,4-naphthoquinone. On the other hand, 1,4-naphthoqui-
none-2,3-dicarbonitrile (4) may act as either as a media-
tor or as a building block in heterocyclization of substi-
tuted hydrazides. The results reported here supplement
the rich of substituted hydrazides 1a-e.
EXPERIMENTAL
6,8,9-Trichloro-7-hydroxy-2-(thiophen-2-yl)benzo[f][1,3,4]-
oxadiazepin-5-(4H)-one (5b). Compound 5b was obtained as
reddish brown crystals (0.258g, 71%), mp 257–259ꢁC (acetoni-
trile). IR: 3470 (OH), 3295 (NH), 1700 (CO), 1630 (C¼¼N),
Mp’s were determined using open glass capillaries on a Gal-
lenkamp melting point apparatus and are uncorrected. The IR
spectra were recorded with a Shimadzu 408 instrument using
potassium bromide pellets. The 1H NMR (400.13 MHz) and
13C NMR (100.6 MHz) spectra were measured in DMSO-d6
using a Bruker AM400 with TMS as an internal standard.
Chemical shifts are expressed as d [ppm], s ¼ singlet, m ¼
multiplet and b ¼ broad. Assignments of carbon resonances
have been supported by DEPT experiments. Mass spectra have
been obtained with Varian MAT CH-7 instrument using elec-
tron impact ionization (70 eV). Elemental analyses have been
determined by the Microanalytical Center, Cairo University,
Egypt. For preparative layer chromatography (plc) 1.0 mm
thick air-dried layers of slurry applied silica gel, Merck Pf254
on 48 cm wide and 20 cm high glass plates were used, zones
were detected by their color and indicator fluorescence
quenching upon exposure to 254 nm light and extracted with
acetone.
Starting materials. Substituted hydrazides 1a-e were pre-
pared according to published procedures, as were 2-thiophene
carbohydrazide (1b), mp 135–137ꢁC (ref. [33] 134–136ꢁC);
furan-2-carbohydrazide (1c), mp 77–79 (ref. [34] 78ꢁC); 2-pyr-
idine carbohydrazide (1d), mp 136–138ꢁC (ref. [35] 137ꢁC);
indole-2-carbohydrazide (1e), mp 243–245ꢁC (ref. [36,37]
246ꢁC) and phenyl carbohydrazide (1a) (Aldrich), 2,3,5,6-tet-
rachloro-1,4-benzoquinone (2) (Aldrich) and 2,3-dichloro-1,4-
naphthoquinone (3) (Aldrich) were used as received. 1,4-Naph-
thoquinone-2,3-dicarbonitrile (4) was prepared from 2,3-
dichloro-1,4-naphthoquinone (3) according to Budni et al [38].
Reaction of substituted hydrazides 1a-e with (2). To a so-
lution of 2 (246 mg, 1 mmol) in dry DMF (15 mL) a solution
of 1a-e (1.0 mmol each) in 5 mL of DMF was added dropwise
over 5 min. at room temperature with stirring and admission
of air. The stirring was continued for 48 h with admission of
air to complete the reaction. The reaction mixture was concen-
trated to drynes. The residue was taken up several times with
cold ethanol (10 mL) and slurry was concentrated again to
remove any residual DMF. The residue was dissolved in ace-
tone (5 mL). This solution in each case was applied to 5 plc-
plates and developed with toluene/ethyl acetate (5:1) for the
run with 1a, toluene/ethyl acetate (4:1) for the runs with 1b-d
and toluene/ethyl acetate (3:1) for the run with 1e to give
numerous colored zones. The two intense of which were
1
1585 (ArAC¼¼C), 1090 (CAOAC). H NMR: d 7.05–7.38 (m,
3H, thiophene-H), 7.79 (br, 1H, oxadiazepine-NH), 9.62 (br,
1H, OH); 13C NMR: d 120.59 (C-5a), 122.42, 123.55, 123.96
(C-6, 8 and 9), 126.27, 127.69, 127.94 (thiophene-CH), 130.16
(thiophene-C), 148.06 (C-9a), 152.61 (C-7), 156.79 (C-2),
169.76 (CO); ms m/z: 362/368 (Mþ, 34), 328 (18), 292 (27),
218 (41), 111 (100), 107 (53), 82 (46); Anal. Calcd. for
C12H5Cl3N2O3S (363.60): C, 39.64; H, 1.39; Cl, 29.25; N,
7.70. Found C, 39.41; H, 1.51; Cl, 29.47; N, 7.54.
6,8,9-Trichloro-7-hydroxy-2-(furan-2-yl)benzo[f][1,3,4]-
oxadiazepin-5-(4H)-one (5c). Compound 5c was obtained as
reddish brown crystals (0.229 g, 66%), mp 207–208ꢁC (aceto-
nitrile). IR: 3455 (OH), 3335 (NH), 1710 (CO), 1625 (C¼¼N),
1085 (CAOAC); 1H NMR: d 7.11–7.46 (m, 3H, furan-H),
7.82 (br, 1H, oxadiazepine-NH), 9.57 (br, 1H, OH); 13C NMR:
d 120.71 (C-5a), 122.19, 123.64, 123.92 (C-6, 8 and 9),
125.98, 126.11 (furan-CH), 141.57, 142.11 (furan-C-2, C-5),
147.96 (C-9a), 152.75 (C-7), 156.68 (C-2), 169.81 (CO); ms
m/z: 346/352 (Mþ, 38), 312 (25), 276 (16), 220 (31), 184 (27),
95 (100), 67 (71); Anal. Calcd. For C12H5Cl3N2O4 (347.54):
C, 41.47; H, 1.45; Cl, 30.60; N, 8.06. Found C, 41.66; H,
1.56; Cl, 30.38; N, 7.87.
6,8,9-Trichloro-7-hydroxy-2-(pyridin-2-yl)benzo[f][1,3,4]-
oxadiazepin-5-(4H)-one (5d). Compound 5d was obtained as
reddish brown crystals (0.247g, 69%), mp 226–228ꢁC (etha-
nol). IR: 3480 (OH), 3315 (NH), 1705 (CO), 1620 (C¼¼N),
1
1590 (ArAC¼¼C), 1080 (CAOAC); H NMR: d 7.48–8.41 (m,
5H, pyridine-H and oxadiazepine-NH), 9.57 (br, 1H, OH); 13C
NMR: d 121.07 (C-5a), 122.31, 123.62, 123.89 (C-6, 8 and 9),
127.89, 128.75, 130.14 (pyridine-CH), 146.35, 147.11 (pyri-
dine C-2, C-6), 148.22 (C-9a), 152.57 (C-7), 156.85 (C-2),
169.73 (CO); ms m/z: 357/363 (Mþ, 21), 323 (18), 287 (34),
195 (47), 106 (83), 78 (100); Anal. Calcd. for C13H6Cl3N3O3
(358.56): C, 43.55; H, 1.69; Cl, 29.66; N, 11.72. Found C,
43.33; H, 1.78; Cl, 29.43; N, 11.87.
2-(1H-Indole-2-yl)-6,8,9-trichloro-7-hydroxy-benzo[f][1,3,4]-
oxadiazepin-5-(4H)-one (5e). Compound 5e was obtained as
reddish brown crystals (0.265g, 67%), mp 271–273ꢁC (metha-
nol). IR: 3475–3280 (OH, NH’s), 1710 (CO), 1630 (C¼¼N),
1595 (ArAC¼¼C), 1090 (CAOAC); 1H NMR: d 6.64 (s, 1H,
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A. A. Hassan, Y. R. Ibrahim, and A. M. Shawky
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indole-CH), 7.12–7.68 (m, 4H, ArAH), 7.86 (br, 1H, oxadiaze-
pine-NH), 9.58 (br, 1H, OH), 11.62 (br, 1H, indole-NH); 13C
NMR: d 99.71(indole-CH), 121.98 (C-5a), 121.87, 123.35,
123.92 (C-6, 8 and 9), 127.14, 127.96 (ArACH), 130.55
(indole-C3a), 134.66, 137.12 (indole C-2 and C-7a), 152.46
(C-7), 156.81 (C-2), 169.80 (CO); MS m/z: 395/361 (Mþ, 29),
331 (26), 295 (38), 242 (21), 186 (12), 144 (62), 116 (76), 92
(100), 77 (83), 65 (41); Anal. Calcd. for C16H8Cl3N3O3
(396.61): C, 48.45; H, 2.03; Cl, 26.82; N, 10.59. Found C,
48.64; H, 1.91; Cl, 27.03; N, 10.77.
idine-CH), 138.42 (C-8a), 140.87 (C-4a), 146.42, 147.83 (pyri-
dine-C-2 and C-6), 152.71 (C-7), 156.84 (C-3), 171.42 (CO);
MS m/z: 366/370 (Mþ, 35), 332 (19), 296 (27), 224 (41), 196
(23), 106 (74), 78 (100); Anal. Calcd. for C15H12Cl2N4O3
(367.19): C, 49.07; H, 3.29; Cl, 19.31; N, 15.26. Found C,
48.84; H, 3.41; Cl, 19.07; N, 15.43.
5,6-Dichloro-7-hydroxy-N,N0-dimethyl-3-(pyridin-2-yl-1H-
benzo[e][1,3,4]oxadiazine-8-carboxamide (6e). Compound 6e
was obtained as brown crystals (0.073g, 18%), mp 301–303ꢁC
(methanol). IR: 3485 (OH), 3340-3295 (NH’s), 1690 (CO),
1630 (C¼¼N), 1600 (Ar-C¼¼C), 1085 (CAOAC); 1H NMR: d
3.41 (s, 6H, N(CH3)2), 6.64 (s, 1H, indole-CH), 7.26–7.81 (m,
5H, ArAH and oxadiazine-NH), 9.62 (br, 1H, OH), 11.71 (br,
1H, indole-NH); 13C NMR: d 36.45 (CH3), 98.95 (indole-CH),
106.88 (C-8), 122.32, 123.41 (C-5 and C-6), 126.37, 127.74
(Ar-CH), 130.71 (indole-C-3a), 135.07, 137.36 (indole-C-2 and
C-7a), 138.53 (C-8a), 141.07 (C-4a), 153.04 (C-7), 156.91 (C-
3), 171.26 (CO); MS m/z: 404/408 (Mþ, 25), 370 (32), 334
(12), 262 (46), 234 (19), 144 (56), 91 (76), 77 (100), 65 (85);
Anal. Calcd. for C18H14Cl2N4O3 (405.23): C, 53.35; H, 3.48;
Cl, 17.50; N, 13.83. Found C, 53.17; H, 3.61; Cl, 17.72; N,
14.05.
Reaction of substituted hydrazides 1a-e with (3). A solu-
tion of 1a-e (1.0 mmol) in 15 mL of dry DMF was added
dropwise with stirring to a solution of 3 (1.0 mmol) in 10 mL
of dry DMF. The reaction mixture was stirring for 72 h, during
which time it turned from faint orange into deep red. The pre-
cipitate of substituted naphtho[2,3-f][1,3,4]oxadiazepine-
5,6,11-(4H)-trione 16 was filtered and washed several times
with cold ethanol, and crystallized from suitable solvent.
2-Phenylnaphtho[2,3-f][1,3,4]oxadiazepine-5,6,11-(4H)-tri-
one (16a). Compound 16a was obtained as reddish brown
crystals (0.280g, 88%), mp 289–291ꢁC (acetonitrile). IR: 3230
(NH), 1710, 1685 (CO), 1620 (C¼¼N), 1585 (ArAC¼¼C), 1090
(CAOAC); 1H NMR: d 7.14–7.76 (m, 5H, ArAH), 7.84 (br,
1H, oxadiazepine-NH), 8.04–8.21 (m, 4H, ArAH); 13C NMR:
d 126.49, 128.84, 129.12, 134.61, 136.66 (ArACH), 131.45,
132.45, 132.17, 141.36 (ArAC), 156.86 (C-2), 169.64 (oxadia-
zepine-CO), 187.44, 187.78 (C-6 and C-11); ms m/z: 318
(Mþ, 46), 213 (26), 185 (61), 105 (81), 104 (76), 77 (100), 65
(67); Anal. Calcd. for C18H10N2O4 (318.28): C, 67.92; H,
3.17; N, 8.80. Found C, 68.14; H, 3.06; N, 9.04.
5,6-Dichloro-7-hydroxy-N,N0-dimethyl-3-phenyl-1H-benzo[e]
[1,3,4]oxadiazine-8-carboxamide (6a). Compound 6a was
obtained as deep red brown crystals (0.062g, 17%), mp 248–
250ꢁC (acetonitrile). IR: 3485 (OH), 3290 (NH), 1690 (CO),
1
1625 (C¼¼N), 1585 (ArAC¼¼C), 1080 (CAOAC); H NMR: d
3.44 (s, 6H, N(CH3)2), 7.24–7.79 (m, 6H, ArAH and oxadia-
zine-NH), 9.67 (br, 1H, OH); 13C: d 36.29 (CH3), 106.83 (C-
8), 122.27, 123.14 (C-5 and C-6), 127.21, 128.54, 130.16 (Ar-
CH), 134.27 (Ar-C), 138.44 (C-8a), 141.11 (C-4a), 152.51 (C-
7), 156.76 (C-3), 171.41 (CO); MS m/z: 365/369 (Mþ, 41),
329 (18), 257 (44), 193 (29), 105 (81), 77 (100), 65 (74);
Anal. Calcd. for C16H13Cl2N3O3 (366.20): C, 52.48; H, 3.58;
Cl, 19.36; N, 11.47. Found C, 52.66; H, 3.45; Cl, 19.59; N,
11.65.
5,6-Dichloro-7-hydroxy-N,N0-dimethyl-3-(thio-phen-2-yl-1H-
benzo[e][1,3,4]oxadiazine-8-carbox-amide (6b). Compound 6b
was obtained as reddish brown crystals (0.067g, 18%), mp
276–278ꢁC (ethanol). IR: 3470 (OH), 3310 (NH), 1685 (CO),
1
1630 (C¼¼N), 1590 (ArAC¼¼C), 1085 (CAOAC); H NMR: d
3.36 (s, 6H, N(CH3)2), 7.11–7.39 (m, 3H, thiophene-H), 7.71
(br, 1H, oxadiazine-NH), 9.70 (br, 1H, OH); 13C: d 36.41
(CH3), 107.12 (C-8), 121.94, 123.32 (C-5 and C-6), 126.22,
127.56, 127.84 (thiophene-CH), 130.12 (thiophene-C), 138.51
(C-8a), 140.97 (C-4a), 152.46 (C-7), 156.81 (C-3), 171.23
(CO); ms m/z: 371/375 (Mþ, 26), 336 (29), 300 (12), 264
(21), 153 (8), 111 (100), 83 (76); Anal. Calcd. for
C14H11Cl2N3O3S (372.23): C, 45.17; H, 2.98; Cl, 19.05; N,
11.29; S, 8.61. Found C, 44.94; H, 3.10; Cl, 18.88; N, 11.41;
S, 8.83.
5,6-Dichloro-7-hydroxy-N,N0-dimethyl-3-(thio-phen-2-yl-1H-
benzo[e][1,3,4]oxadiazine-8-carbox-amide (6c). Compound 6c
was obtained as brown crystals (0.078g, 22%), mp 235–237ꢁC
(ethanol). IR: 3480 (OH), 3300 (NH), 1680 (CO), 1625
2-(Thiophen-2-yl)naphtho[2,3-f][1,3,4]oxadiaz-epine-5,6,11-
(4H)-trione (16b). Compound 16b was obtained as brown
crystals (0.272 g, 84%), mp 307–309ꢁC (ethanol). IR: 3245
(NH), 1715, 1680 (CO), 1625 (C¼¼N), 1585 (Ar-C¼¼C), 1080
(C-O-C); 1H NMR: d 7.08–7.46 (m, 3H, thiophene-H), 7.80
(br, 1H, oxadiazepine-NH), 8.05–8.19 (m, 4H, ArAH); 13C
NMR: d 126.23, 127.76, 128.33, (thiophene-CH), 129.36,
136.94 (Ar-CH), 131.64, 131.16, 141.19 (ArAC), 156.80 (C-
2), 169.58 (oxadiazepine-CO), 187.39, 187.68 (C-6 and C-11);
ms m/z: 324 (Mþ, 23), 213 (34), 185 (48), 111 (100), 104
(56), 77 (86), 65 (61); Anal. Calcd. for C16H8N2O4S (324.31):
C, 59.26; H, 2.49; N, 8.64; S, 9.89. Found C, 59.09; H, 2.61;
N, 8.43; S, 10.04.
1
(C¼¼N), 1590 (ArAC¼¼C), 1085 (CAOAC); Hnmr: d 3.40 (s,
6H, N(CH3)2), 6.95–7.35 (m, 3H, furan-H), 7.69 (br, 1H, oxa-
diazine-NH), 9.67 (br, 1H, OH); 13C: d 36.38 (CH3), 106.91
(C-8), 122.18, 123.27 (C-5 and C-6), 125.96, 126.47 (furan-
CH), 138.36 (C-8a), 141.12 (C-4a), 142.76, 143.63 (furan-C-2
and C-5), 152.64 (C-7), 156.77 (C-3), 171.34 (CO); MS m/z:
355/359 (Mþ, 27), 320 (42), 284 (18), 212 (37), 117 (52), 95
(100), 67 (68); Anal. Calcd. for C14H11Cl2N3O4 (356.16): C,
47.21; H, 3.11; Cl, 19.91; N, 11.80. Found C, 47.44; H, 2.98;
Cl, 20.08; N, 12.02.
5,6-Dichloro-7-hydroxy-N,N0-dimethyl-3-(pyridin-2-yl-1H-
benzo[e][1,3,4]oxadiazine-8-carboxamide
(6d). Compound
6d was obtained as brown crystals (0.062g, 17%), mp 261–
263ꢁC (acetonitrile). IR: 3490 (OH), 3315 (NH), 1690 (CO),
1630 (C¼¼N), 1585 (ArAC¼¼C), 1080 (CAOAC); 1H: d 3.38
(s, 6H, N(CH3)2), 7.36A8.48 (m, 5H, pyridine-H and oxadia-
zine-NH), 9.74 (br, 1H, OH); 13C: d 36.44 (CH3), 107.09 (C-
8), 122.28, 123.46 (C-5 and C-6), 127.16, 128.91, 130.28 (pyr-
2-(Furan-2-yl)naphtho[2,3-f][1,3,4]oxadiazepine-5,6,11-(4H)-
trione (16c). Compound 16c was obtained as brown crystals
(0.253 g, 82%), mp 274–276ꢁC (ethanol). IR: 3235 (NH),
1710, 1690 (CO), 1620 (C¼¼N), 1590 (ArAC¼¼C), 1085
(CAOAC); 1H: d 6.97–7.38 (m, 3H, furan-H), 7.78 (br, 1H,
oxadiazepine-NH), 8.00–8.22 (m, 4H, ArAH); 13C NMR: d
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
Investigation of Interaction of Benzoquinones and Naphthoquinones with
Substituted Hydrazides
123
126.08, 126.26 (furan-CH), 129.54, 136.89 (ArACH), 131.55,
131.96, 140.87 (ArAC), 141.62, 142.26 (furan-C-2 and C-5),
156.85 (C-2), 169.84 (oxadiazepine-CO), 187.46, 187.72 (C-6
and C-11); ms m/z: 308 (Mþ, 32), 213 (28), 185 (57), 157
(21), 104 (71), 95 (63), 77 (100), 65 (84); Anal. Calcd. for
C16H8N2O5 (308.25): C, 62.34; H, 2.62; N, 9.09. Found C,
62.51; H, 2.77; N, 8.83.
C, 68.14; H, 3.49; N, 13.24. Found C, 67.88; H, 3.61; N,
13.40.
3-Amino-2-(thiophen-2-carbonyl)-2H-benzo[f]-indazole-
4,9-dione (17b). Compound 17b was obtained as yellow crys-
tals (0.242 g, 75%), mp 295–297ꢁC (acetonitrile). IR: 3335
(NH2), 1690, 1660 (CO), 1625 (C¼¼N), 1590 (Ar-C¼¼C); 1H
NMR: d 6.67 (br, 2H, NH2), 7.14–7.52 (m, 3H, thiophene-H),
8.05–8.19 (m, 4H, ArAH); 13C NMR: d 100.89 (C-3a),
126.72, 129.33, 129.78, 130.12, 136.44 (ArACH and thio-
phene-CH), 131.58, 132.29 (ArAC and thiophene-C), 140.08
(C-9a), 153.36 (C-3), 165.46 (CO), 187.76 (C-9), 188.54 (C-
4); ms m/z: 323 (Mþ, 41), 212 (56), 184 (44), 111 (100), 104
(62), 77 (83), 65 (74); Anal. Calcd. for C16H9N3O3S (323.33):
C, 59.44; H, 2.81; N, 13.00; S, 9.92. Found C, 59.26; H, 2.94;
N, 12.82; S, 10. 13.
3-Amino-2-(furan-2-carbonyl)-2H-benzo[f]-indazole-4,9-
dione (17c). Compound 17c was obtained as yellow crystals
(0.209 g, 68%), mp 259–261ꢁC (ethanol). IR: 3330 (NH2),
1685, 1665 (CO), 1620 (C¼¼N), 1590 (ArAC¼¼C), 1080 (C-
O-C); 1H NMR: d 6.69 (br, 2H, NH2), 7.08–7.46 (m, 3H,
furan-H), 8.08-8.24 (m, 4H, ArAH); 13C NMR: d 101.14 (C-
3a), 126.13, 126.76, 129.41, 136.28 (ArACH and furan-CH),
131.64 (ArAC), 139.90 (C-9a), 147.42, 148.51 (furan-C-2
and C-5), 153.29 (C-3), 165.65 (CO), 187.89 (C-9), 188.74
(C-4). ms m/z: 307 (Mþ, 59), 212 (38), 184 (61), 104 (72),
95 (86), 77 (100), 65 (76); Anal. Calcd. for C16H9N3O4
(307.26): C, 62.54; H, 2.95; N, 13.68. Found C, 62.37; H,
3.10; N, 13.87.
2-(Pyridin-2-yl)naphtho[2,3-f][1,3,4]oxadiazepine-5,6,11-(4H)-
trione (16d). Compound 16d was obtained as brown crystals
(0.255 g, 80%), mp 297-299ꢁC (acetonitrile). IR: 3245 (NH),
1705, 1690 (CO), 1625 (C¼¼N), 1585 (ArAC¼¼C), 1090
1
(CAOAC); H NMR: d 7.36–8.49 (m, 9H, ArAH, pyridine-H
and oxadiazepine-NH); 13C NMR: d 126.54, 128.73 (pyri-
dine-CH), 129.49, 130.37, 136.94 (Ar-CH and pyridine-CH),
131.57 (Ar-C), 146.39, 147.81 (pyridine-C-2 and C-6),
156.82 (C-2), 169.64 (oxadiazepine-CO), 187.51, 187.80 (C-6
and C-11); ms m/z: 319 (Mþ, 28), 213 (41), 185 (64), 157
(22), 106 (88), 104 (73), 77 (100), 65 (56); Anal. Calcd. for
C17H9N3O4 (319.27): C, 63.95; H, 2.84; N, 13.16. Found C,
64.16; H, 2.71; N, 12.98.
2-(1H-Indol-2-yl)naphtho[2,3-f][1,3,4]oxadiaz-epine-5,6,11-
(4H)-trione (16e). Compound 16e was obtained as reddish
brown crystals (0.282 g, 79%), mp 331–333ꢁC (methanol). IR:
3330-3240 (NH’s), 1710, 1685 (CO), 1630 (C¼¼N), 1600
1
(ArAC¼¼C), 1085 (CAOAC); H NMR: d 6.61 (s, 1H, indole-
CH), 7.16–7.64 (m, 4H, ArAH), 7.82 (br, 1H, oxadiazepine-
NH), 8.05–8.27 (m, 4H, ArAH), 11.71 (br, 1H, indole-NH);
13C NMR: d 99.63 (indole-CH), 127.26, 129.41, 136.22,
137.38 (ArACH), 130.26, 131.66, 134.27, 139.26 (ArAC and
indole-C-2), 156.78 (C-2), 169.75 (oxadiazepine-CO), 187.48,
187.73 (C-6 and C-11); ms m/z: 357 (Mþ, 34), 213 (26), 185
(54), 144 (62), 104 (57), 91 (74), 77 (100), 65 (63); Anal.
Calcd. for C20H11N3O4 (357.32): C, 67.23; H, 3.10; N, 11.76.
Found C, 67.06; H, 2.97; N, 11.89.
3-Amino-2-picolinoyl-2H-benzo[f]indazole-4,9-dione
(17d)C. ompound 17d was obtained as yellow crystals (0.229 g,
72%), mp 276-278ꢁC (acetonitrile). IR: 3335 (NH2), 1685,
1
1660 (CO), 1620 (C¼¼N), 1585 (ArAC¼¼C). H NMR: d 6.68
(br, 2H, NH2), 7.56–8.48 (m, 8H, ArAH and pyridine-H). 13C
NMR: d 100.96 (C-3a), 126.43, 128.51, 129.55, 130.12,
136.34 (ArACH and pyridine-CH), 131.59 (ArAC), 139.81 (C-
9a), 147.86, 148.62 (pyridine-C-2, C-6), 153.37 (C-3), 165.55
(CO), 187.75 (C-9), 188.64 (C-4). ms m/z: 318 (Mþ, 62), 212
(53), 184 (67), 106 (100), 104 (76), 77 (83), 65 (64).
C17H10N4O3 (318.29): C, 64.15; H, 3.17; N, 17.60. Found C,
63.96; H, 3.28; N, 17.76.
Reactions of substituted hydrazides 1a-e with (4). A solu-
tion of 1a-e (1.0 mmol) in 15 mL of dry DMF was added
dropwise with stirring to a solution of 1,4-naphthoquinone-
2,3-dicarbonitrile (4) (208 mg, 1.0 mmol) in 10 mL of dry
DMF. The reaction colour changed gradually from green to
purple and latter turns into brown colour. The stirring was
continued for 72 h with admission of air to complete the
reaction. The reaction mixture was concentrated and the resi-
due was then separated by plc using toluene/ethyl acetate
(5:1) for the runs with (1a-d) and toluene/ethyl acetate (3:1)
for the run with (1e) to give numerous zones, two intense of
which were removed and extracted. The fastest migrating one
which quenched all indicator fluorescence upon exposure to
254nm UV-light contained diacylhydrazines 18a-e. The slow-
est migrating zone (which is always characterized by deep
yellow colour) contained substituted benzo[f]- indazolediones
17a-e.
3-Amino-2-benzoyl-2H-benzo[f]indazole-4,9-dione (17a).
Compound 17a was obtained as deep yellow crystals (0.222 g,
70 %), mp 271–273ꢁC (ethanol). IR: 3345 (NH2), 1685, 1660
(CO), 1620 (C¼¼N), 1585 (Ar-C¼¼C); 1H NMR: d 6.71 (br,
2H, NH2), 7.28–7.77 (m, 5H, ArAH), 8.06–8.22 (m, 4H,
ArAH); 13C NMR: d 101.16 (C-3a), 126.52, 128.32, 129.26,
133.12, 136.51 (ArACH), 130.76, 131.44 (Ar-C), 139.86 (C-
9a), 153.46 (C-3), 165.55 (CO), 187.82 (C-9), 188.68 (C-4);
ms m/z: 317 (Mþ, 52), 212 (41), 184 (26), 105 (100), 104
(76), 77 (81), 65 (72); Anal. Calcd. for C18H11N3O3 (317.30):
3-Amino-2-(1H-indole-2-carbonyl)-2H-benzo[f]-indazole-
4,9-dione (17e). Compound 17e was obtained as yellowish
brown crystals (0.235 g, 66%), mp 324–326ꢁC (acetonitrile).
IR: 3340, 3270 (NH2, NH), 1690, 1665 (CO), 1625 (C¼¼N),
1590 (Ar-C¼¼C); 1H NMR: d 6.59 (s, 1H, indole-CH), 6.73
(br, 2H, NH2), 7.28–7.83 (m, 4H, ArAH), 8.05–8.26 (m, 4H,
ArAH), 11.69 (br, 1H, indole-NH); 13C NMR: d 99.74
(indole-C-3), 101.46 (C-3a), 126.46, 127.29, 129.41, 130.29,
136.36 (ArACH), 130.52, 131.64 (ArAC), 137.86 (indole-C-
2), 138.68 (indole-C-7a), 140.11 (C-9a), 153.48 (C-3), 165.73
(CO), 187.75 (C-9), 188.65 (C-4); ms m/z: 356 (Mþ, 39), 212
(26), 184 (55), 144 (86), 104 (77), 91 (89), 77 (100), 65 (62);
Anal. Calcd. for C20H12N4O3 (356.33): C, 67.41; H, 3.39; N,
15.72. Found C, 67.22; H, 3.27; N, 15.89.
N0-Benzoylbenzohydrazide (18a). Yield (0.038g, 16%), mp
239–241oC (ref. [39,40] 237–238ꢁC). 1H NMR: d 7.26–7.40
(m, 3H, ArAH), 7.44–7.64 (m, 4H, ArAH), 7.78–7.83 (m, 3H,
ArAH), 10.68 (br, 2H, NH).
N0-(Thiophene-2-carbonyl)thiophen-2-hydrazide (18b). Yield
(0.035g, 14%), mp 276–278ꢁC (ref. [41,42] 274–277oC). 1H
NMR: d 7.19–7.58 (m, 6H, thiophene-H), 10.62 (br, 2H, NH).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

124
A. A. Hassan, Y. R. Ibrahim, and A. M. Shawky
Vol 47
N0-(Furan-2-carbonyl)furan-2-hydrazide (18c). Yield (0.026g,
[19] Hassan, A. A.; Mourad, A. E.; Abou-Zied, A. H. Arkivoc
2007, i, 222.
[20] Hassan, A. A.; Aly, A. A.; El-Sheref, E. M. Arkivoc 2007,
xiv, 229.
[21] Hassan, A. A.; Refaey, S. M.; Shehatta, H. S. Arkivoc
2007, xv, 265.
12%), mp 240–242ꢁC (ref. [44] 238–239ꢁC). 1H NMR: d
7.05–7.52 (m, 6H, furan-H), 10.66 (br, 2H, NH).
N0-Picolinoylpicolinohydrazide (18d). Yield (0.036mg,
15%), mp 224–226ꢁC (ref. [44] 224–225ꢁC). 1H NMR: d
7.52–8.37 (m, 8H, pyridine-H), 10.65 (br, 2H, NH).
[22] Lee, H.–J.; Park, S.–Y.; Kim, J. S.; Song, H. M.; Suh, M.–
E.; Lee, C.–O. Bioorg Med Chem 2003, II, 4791.
[23] Gomez-Monterrey, I.; Campiglia, P.; Grieco, P.; Diurno, M.
V.; Bolognese, A.; Lacolla, P.; Novellino, E. Bioorg Med Chem 2003,
II, 3769.
N0-(1H-Indole-2-carbonyl)-1H-indole-2-hydrazide (18e). Yield
(0.035g, 11%), mp 355–357ꢁC (ref. [44] 356.5–357.5ꢁC). 1H
NMR: d 6.62 (s, 2H, indole-CH), 7.30–7.84 (m, 8H, ArAH),
10.66 (br, 2H, NH), 11.67 (br, 2H, indole-NH).
[24] Lee, H.–J.; Suh, M. E.; Lee, C. O. Bioorg Med Chem 2003,
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1995, 41, 665.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet