Metal-assisted oxidative cyclization of arylamidrazones I. Synthesis of 3-acetyl-1,4-dihydro-1-phenyl-1,2,4-benzotriazine

Article abstract of DOI:10.1007/s00706-006-0465-5

In the presence of RuCl₃, N-phenylamidrazone underwent oxidative cyclization into 1,4-dihydro-1-phenyl-1,2,4-benzotriazine, the structure of which is established by spectral and X-ray diffraction data. Springer-Verlag 2006.

Full text of DOI:10.1007/s00706-006-0465-5

Monatshefte f€ur Chemie 137, 745–750 (2006)
DOI 10.1007/s00706-006-0465-5
Metal-Assisted Oxidative Cyclization
of Arylamidrazones I. Synthesis
of 3-Acetyl-1,4-dihydro-1-phenyl-1,2,4-
benzotriazine
Mousa Z. Al-Noaimi1, Raid J. Abdel-Jalil1, Mustafa M. El-Abadelah2,
Salim F. Haddad2, Younis N. H. Baqi3, and Wolfgang Voelter3;ꢀ
1
Chemistry Department, Faculty of Science, The Hashemite University, Zarka, Jordan
2
Chemistry Department, Faculty of Science, University of Jordan, Amman, Jordan
3
€ €
€
Interfakultares Institut fur Biochemie der Universitat Tubingen, Tubingen, Germany
€
€
Received March 13, 2006; accepted March 13, 2006
Published online May 15, 2006 # Springer-Verlag 2006
Summary. In the presence of RuCl3, N-phenylamidrazone underwent oxidative cyclization into 1,4-
dihydro-1-phenyl-1,2,4-benzotriazine, the structure of which is established by spectral and X-ray
diffraction data.
Keywords. Arylamidrazones; Ruthenium(III) chloride; Dihydro-1,2,4-benzotriazines.
Introduction
Functionally-substituted arylamidrazones are utilized for the construction of var-
ious condensed aza-heterocycles [1, 2]. Surprisingly, the reaction of 1-(phenyl-
amino)-1-(phenylhydrazono)-2-propanone (2) with ruthenium(III) chloride led to
the formation of 3-acetyl-1,4-dihydro-1-phenyl-1,2,4-benzotriazine (3, Scheme 1),
as evidenced from NMR and X-ray data (vide infra). This class of heterocyclic
compounds is of interest generating stable dihydro-1,2,4-benzotriazinyl free radi-
cals (4, Fig. 1) [3] and as non-steroidal anti-inflammatory drugs (e.g. azapropazone
(5) [4], Fig. 1) used to treat various forms of arthritis.
Results and Discussion
Addition reactions of a variety of nucleophilic species onto nitrile imines (gener-
ated in situ by the action of triethylamine on hydrazonyl chorides) provide direct
ꢀ
Corresponding author. E-mail: wolfgang.voelter@uni-tuebingen.de

746
M. Z. Al-Noaimi et al.
Scheme 1
Fig. 1. Structures of dihydro-1,2,4-benzotriazinyl free radicals (4) and azapropazone (5)
access to diverse acyclic systems [5–7]. In this way, 2 was prepared via interaction
of 1-phenylhydrazono-1-chloropropanone (1) with aniline (Scheme 1) following
Ref. [8]. Direct interaction of 2 with RuCl3 in ethanol gave 3-acetyl-1,4-dihydro-1-
phenyl-1,2,4-benzotriazine (3) in 52% yield. 1H and 13C NMR spectral data and X-
ray diffraction measurements confirm the assigned structure of 3 and are given in
the experimental section.
In the present study, single crystal X-ray diffraction measurements for 3 were
performed, and the results are listed in Tables 1 and 2 and shown in Fig. 2. The
dihydrotriazine moiety comprising N1, C13, N3, N2, C6, and C1 exhibits a sig-
nificant ring-puckering with a root mean square deviation of these six fitted atoms
˚
of 0.1381; the hydrogen atom positioned at N1 is 0.4957 A out of the plane of the
dihydrotriazine moiety. The half heteroring encampassing N1, C1, C6, and N2 is
nearly planar to the benzo-fused ring (C1–C6) with a dihedral angle of 1.2ꢁ (0.2),
while the second half heteroring (comprising N1, C13, N3, N2) shows a dihedral

Metal-Assisted Oxidative Cyclization
747
Table 1. Summary of the crystal data and structure refinement parameters for 3
Empirical formula
Formula weight
Temperature=K
C15H13N3O
251.28 Da
293(2)
˚
Wavelength=A
0.71073
Crystal system
Space group
Monoclinic
C2=c
Unit cell dimensions
˚
a=A
20.367(4)
˚
b=A
17.319(4)
˚
c=A
7.4310(15)
ꢀ=ꢁ
101.37(3)
3
˚
Volume=A
2569.7(9)
Z
8
Calculated density=g cmꢂ3
Absorption coefficient=mmꢂ1
F (000)
1.299
0.085
1056
Theta range for data collection=ꢁ
Completeness to ꢁ ¼ 25.03ꢁ
Index range
2.04–25.03
90.8%
ꢂ24ꢃhꢃ24; ꢂ20ꢃkꢃ20; ꢂ8ꢃ1ꢃ7
Reflections collected
Independent reflections
Weight scheme
8480
2062 [Rint ¼ 0.0740]
Calcd w ¼ 1=[ꢂ2 (F0)2 þ (0.0701P)2 þ 0.0000P]
where P ¼ [(F0)2 þ 2(Fc)2]=3
2062=0=172
0.914
Data=restraints=parameters
Goodness-of-fit on F2
Final R indices [I>2ꢂ (I)]
R Indices (all data)
R1 ¼ 0.0734, wR2 ¼ 0.1649
R1 ¼ 0.1872, wR2 ¼ 0.1991
0.280
ꢂ3
ꢂ3
˚
Largest difference peak=e ꢄ A
˚
Largest difference hole=e ꢄ A
ꢂ0.177
angle of 27.4ꢁ (0.2) with respect to the first half. In other words, there is a folding
of 27.4ꢁ along the
axis bisecting the dihydrotriazine ring (Fig. 1). More-
over, the dihedral angle between the two benzenoid (phenylene and phenyl) rings is
59.7ꢁ (0.1), while the dihedral angle between the plane containing the acyl car-
bonyl group, namely C13, C14, C15, and O1, and that of the dihydrotriazine ring is
9.9ꢁ (0.2). Currently, we are exploring the scope and generality of this one-pot
metal-assisted reaction as well as the consequent mechanistic aspects, and the
results will be reported in due course.
Experimental
Rhuthenium(III) chloride and 3-chloro-2,4-pentanedione were purchased from Acros. Melting points
1
were determined on a Gallenkamp electrothermal melting temperature apparatus. H and 13C NMR
spectra were measured on a Bruker DPX-300 instrument with TMS as internal reference. EIMS spectra
were obtained using a Finnigan MAT TSQ-70 spectrometer at 70eV and an ion source temperature of
200ꢁC. IR spectra were recorded as KBr discs on a Nicolet Impact-400 FT-IR spectrophotometer.

748
M. Z. Al-Noaimi et al.
Fig. 2. Molecular stucture of 3-acetyl-1,4-dihydro-1-phenyl-1,2,4-benzotriazine (3); thermal ellip-
soids are drawn at the 50% probability level; numbering of the atoms in this ORTEP plot (and in
Table 1) is arbitrary, being different from the IUPAC numbering adopted in Scheme 1
Microanalyses were performed at the Microanalytical Laboratory of the Chemistry Department of
Hashemite University, Zarka-Jordan, and the results agreed with the calculated values within experi-
mental error (ꢅ0.4%).
1-Phenylhydrazono-1-chloropropanone (1)
The hydrazonoyl chloride 1 was previously characterized and is prepared in this study via the Japp–
Klingemann reaction [9] that involves direct coupling of benzenediazonium chloride with 3-chloro-2,4-
pentanedione following the standard procedure [10].
1-(Phenylamino)-1-(phenylhydrazono)-2-propanone (2)
This compound is prepared via direct interaction of 1 with aniline in methanol in the presence of
triethylamine following the procedure of Ref. [8]. Yield 94%; mp 95ꢁC (Ref. [8] yield 96%, mp 94ꢁC).
3-Acetyl-1,4-dihydro-1-phenyl-1,2,4-benzotriazine (3, C15H13N3O)
A mixture of 266 mg RuCl3 (1.0mmol) and 253 mg 2 (1.0mmol) in 200 cm3 absolute ethanol was
refluxed for 4 h. Then, additional 1.0 mmol 2 was added to the reaction mixture, which was further
heated for 1 h. Excess LiCl (500 mg, 12 mmol) was then introduced and the reaction mixture was re-
fluxed for l h. The solvent was evaporated in vacuo and the residue taken up in CH2Cl2. The resulting
solution was washed with water (3ꢆ30cm3) to remove unreacted RuCl3, dried (MgSO4), and the
solvent removed under reduced pressure. The residual brown solid was purified by column chroma-
tography over alumina using CH2Cl2=acetonitrile (3=1, v=v) as eluent. Yield 52%; mp 173–174ꢁC;
1H NMR (300MHz, CDCl3): ꢃ ¼ 2.39 (s, CH3), 6.34 (m, H-5 þ H-8 þ NH), 6.61 (dd, J ¼ 7.3, 7.4 Hz,
H-7), 6.71 (dd, J ¼ 7.3, 7.4 Hz, H-6), 7.19 (tt, J ¼ 2.0, 6.7 Hz, H-40), 7.41 (m, H-20, H-60, H-30, H-50);
13C NMR (75.4 MHz, CDCl3): ꢃ ¼ 23.6 (CH3), 112.6 (C-8), 113.7 (C-5), 122.9 (C-20 þ C-60), 123.8
(C-7), 124.6 (C-6), 125.3 (C-40), 129.2 (C-30 þ C-50), 132.8 (C-10), 142.9 (C-8a), 143.5 (C-4a), 149.6
(C-3), 191.3 (C¼O); MS (EI, 70 eV): m=z (%) ¼ 250 (100) [Mþ-1], 208 (65) [Mþ-O¼CCH3], 181 (18)
[Mþ-1-N¼C–C(O)CH3].

Metal-Assisted Oxidative Cyclization
749
Crystal Structure Determination of 3
Crystals (brown, parallelpiped) were obtained by allowing a hot solution of 3 in ethanol=H2O (5=1,
v=v) to stand at rt for 4–5 d (crystal dimensions: 0.30ꢆ0.20ꢆ0.05 mm3). Crystal data collection was
made on a Rigaku MSC Mercury CCD diffractometer using graphite-monochromated Mo–Kꢄ radia-
tion. Data collection and reduction were performed using Crystal Clear 1.3.5 [11] and Crystal Structure
2.00 [12]. The data were then transferred via interface command to SHELXTL [13] and solved by
direct phasing using SHELXS [14] and refined using SHELXL [15]. Graphics and calculations were
performed by SHELXP, and Table 1 was generated using SHELXCIF. All non-hydrogen atoms were
refined anisotropically by full-matrix least-squares procedure based on F2 using all unique data. The
hydrogen atoms were placed geometrically and then refined isotropically using a ‘riding model’ with
Uiso constrained to be 1.2 Ueq of the carrier atom. Crystallographic data for the structural analysis of 3
have been deposited with the Cambridge Crystallographic Data Center under the depository no. CCDC
– 275956. Copies of further information may be obtained free of charge from the Director, CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (Fax: þ44-1223-336033, e-mail: deposit@ccdc.cam.ac.uk, or
http:==www.ccdc.cam.ac.uk).
Acknowledgements
Financial support by the Hashemite University and the University of Jordan is gratefully appreciated.
€ €
We are grateful to DAAD and Internationales Buro of BMBF, Julich, for fellowships granted to R.J.A.-J.
and M.M.E.-A.
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