The structure of 2-phenylazo-5-(trichloro-1,4-benzoquinonyl)-thiazole

Article abstract of DOI:10.1007/s10593-009-0312-9

X-ray diffraction crystallographic analysis was used to determine the structure of 2-phenylazo-5-(trichloro- 1,4-benzoquinonyl)thiazole and these results were used to establish that 2-phenylazo-5-(2,5-dihydroxy- 3,4,6-trichlorophenyl)thiazole is formed in

Full text of DOI:10.1007/s10593-009-0312-9

Chemistry of Heterocyclic Compounds, Vol. 45, No. 5, 2009
THE STRUCTURE OF 2-PHENYLAZO-
5-(TRICHLORO-1,4-BENZOQUINONYL)-
THIAZOLE*
N. Batenko1**, S. Belyakov2, and R. Valters1
X-ray diffraction crystallographic analysis was used to determine the structure of 2-phenylazo-5-(trichloro-
1,4-benzoquinonyl)thiazole and these results were used to establish that 2-phenylazo-5-(2,5-dihydroxy-
3,4,6-trichlorophenyl)thiazole is formed in the reaction of 3,4,6,7-tetrachloro-2,5-dihydroxy-3 2,3-dihydro-
benzo[b]furan with 1-phenylthiosemicarbazide.
Keywords: 1,4-benzoquinone, 2,3-dihydrobenzo[b]furan, thiazole.
Heterocyclic derivatives of 1,4-benzoquinones have generated considerable interest due to the presence
of both an electron-withdrawing fragment (quinone) and electron-donor fragment (heterocycle) in a single
molecule. Many derivatives of 1,4-benzoquinones and 1,4-naphthoquinones have pharmacological activity. The
methods and properties of these compounds have been reviewed by Spyroudis [1] and in our previous work [2].
In the present communication, we present refined data on the structure of the product of the reaction of
3,4,6,7-tetrachloro-2,5-dihydroxy-2,3-dihydrobenzo[b]furan (1) with 1-phenylthiosemicarbazide. Dihydro-
benzofuran 1 is the cyclic form of the o-hydroxyphenyl derivative of α-chloroacetaldehyde [3, 4]. The major
products of the reactions between 1-substituted thiosemicarbazides and α-halocarbonyl compounds are
derivatives of 4H-1,3,4-thiadiazine [5].
In previous work [6, 7], we showed that two compounds are formed in the reaction of
dihydrobenzofuran 1 with 1-phenylthiosemicarbazide, namely, 2-amino-4-phenyl-6-(3,4,6-trichloro-2,5-di-
hydroxyphenyl)-4H-1,3,4-thiadia-zine (2) and 2-amino-5-(3,4,6-trichloro-2,5-dihydroxyphenyl)thiazole (3). The
1
structure of 2 was assigned using data derived from elemental analysis and H NMR (90 MHz), IR, and
UV spectroscopy. However, a study of subsequent transformations of compound 2 cast some doubt on the
1
correctness of this assignment and we decided to carry out a further investigation. The data of the H NMR
13
spectrum at 200 MHz and C NMR spectrum at 100 MHz permitted us to refine the structure of compound 2
1
and assign the structure of 2-phenylazo-5-(3,4,6-trichloro-2,5-dihydroxyphenyl)- thiazole (5). The H NMR
spectrum clearly shows two signals for different OH groups at 10.13 and 9.94 ppm but lacks signals for an NH2
_______
* Dedicated to Professor Andris Strakovs on the occasion of his seventy-fifth jubilee.
** To whom correspondence should be addressed, e-mail: nbatenko@hotmail.com.
1Riga Technical University, Riga, LV-1048, Latvia.
2Latvian Institute of Organic Synthesis, Riga, LV-1006, Latvia, e-mail: serg@osi.lv.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 766-771, May, 2009. Original
article submitted April 14, 2009.
606
0009-3122/09/4505-0606©2009 Springer Science+Business Media, Inc.

group. The downfield shift of the signals of the ortho protons of the benzene ring indicate their proximity to an
electron-withdrawing substituent and correspond to the position of the signals of azobenzene protons [8].
Ph
N
OH
OH
N
Cl
Cl
Cl
Cl
Cl
HO
Cl
PhNHNHC(S)NH2
EtOH
S
NH2
+
OH
O
Cl
2
N
1
OH
NH2
Cl
Cl
S
+
Cl
OH
3
In previous work [3], we showed that the synthesis of 4H-1,3,4-thidiazines is often complicated by the
formation of cyclization sideproducts though we were unable to correlate the formation of any of these products
with the structure of the starting compounds.
In our present case, in all likelihood, formation of the thiazole ring initially involves replacement of the
chlorine atom at C(3) of dihydrobenzofuran 1 followed by opening of the dihydrobenzofuran ring and formation
of the thiazole N(3)–C(4) bond. The structure of compound 2 presupposes formation of a bond with the
N(1) atom of 1-phenylthiosemicarbazide. The structure of product 5 indicates that the cyclization proceeds at the
N(4) atom of the thiosemicarbazide. Disproportionation of the 1,2-disubstituted hydrazine leads to
hydroquinone 5 and accounts for the appearance of compound 3.
NH
O
NH
NHNHPh
OH
Cl
Cl
S
NHNHPh
OH
Cl
Cl
HO
Cl
PhNHNHC(S)NH2
EtOH
S
1
O
Cl
OH
N
N
OH
Cl
OH
H
N
N
Cl
S
S
N
N
Ph
Ph
H
3
+
– PhNH2
Cl
OH
4
Cl
Cl
Cl
OH
5
N
O
O
N
Cl
Cl
S
FeCl3/DMF/H2O
N
Ph
Cl
6
607

The oxidation of hydroquinone 5 gives 2-phenylazo-5-(trichloro-1,4-benzoquinonyl)thiazole (6).
Suitable monocrystals may be grown from methylene chloride and the structure of this compound was
definitively solved by X-ray diffraction crystallographic analysis.
Figure 1 shows the molecular structure of azothiazole 6 with thermal vibration ellipsoids and the
designation of the atoms. The major bond lengths and valence angles are given in Table 1. This molecule has a
planar conformation. All the atoms lie in a single plane within the margin of error the substituents at the
azogroup are in trans position. This structure of azothiazole 6 is very tentative: the conjugation system
encompasses the entire molecule. Thus, there are no pure double bonds or pure single bonds in this structure.
The mean bond length of the chlorine atoms with the corresponding carbon atoms in the benzoquinone fragment
(1.711(9) Å) indicates that the conjugation system in this molecule also extends to the chlorine atoms.
Fig. 1. Three-dimensional model of azothiazole 6 according to X-ray diffraction
crystallographic data.
Fig. 2. Fragment of the crystal structure of azothiazole 6.
Figure 2 shows a fragment of the packing of molecules of azothiazole 6 in the crystal lattice. An
intermolecular π-π stacking interaction is observed between the molecules in the crystal structure leading to the
formation of stacks of molecules along the crystallographic y-axis. The shortest contact in the molecular stacks
608

TABLE 1. Main Bond Lengths (l) and Valence Angles (ω) of 6.
Bond
l, Å
Angle
ω, deg
S(1)–C(2)
S(1)–C(5)
C(2)–N(3)
C(4)–C(5)
C(2)–N(6)
N(6)–N(7)
N(7)–C(8)
C(5)–C(14)
C(14)–C(15)
C(15)–C(16)
1.706(9)
1.754(9)
C(2)–S(1)–C(5)
S(1)–C(2)–N(3)
N(3)–C(4)–C(5)
C(4)–C(5)–S(1)
C(2)–N(6)–N(7)
N(6)–N(7)–C(8)
C(4)–C(5)–C(14)
C(5)–C(14)–C(15)
C(14)–C(15)–C(16)
C(15)–C(16)–O(21)
89.6(5)
116.4(7)
118.8(9)
106.6(7)
108.6(8)
115.0(8)
131.6(9)
126.0(8)
122.3(9)
119.4(10)
1.324(12)
1.384(13)
1.414(12)
1.263(11)
1.411(12)
1.457(13)
1.356(13)
1.505(13)
TABLE 2. Main Crystallographic Data for Azothiazole 6 and Refinement
Characteristics for the Crystal Structure
Empirical formula
Molecular mass
Crystal form
C15H6Cl3N3O2S
398.655
Needle
Crystal size, mm
Symmetry
0.01 × 0.03 × 0.37
Monoclinic
Unit cell parameters:
a, Å
11.427(1)
5.3467(5)
13.179(2)
106.991(4)
770.0(1)
P21
b, Å
c, Å
β, deg.
Unit cell volume, V, Å3
Space group
Number of molecules in unit cell, Z
F(000)
2
400
Density, ρcalc, g/cm3
Maximum angle, 2θmax, град.
Miller index ranges
1.719
55.0
-14≤h≤14
-6≤k≤5
-17≤l≤16
0.744
Absorption coefficient, µ, mm-1
Total number of reflections
Number of independent reflections
Number of reflections with I > 2σ(I)
R-Factor
5467
3287
2055
0.0534
0.1033, 0.2213
207
R-indices over all reflections (R1, wR2)
Number of refined parameters
GOOF
0.974
(∆/σ)max
0.001
(3.202(11) Å) is found between C(18) and O(21) of adjacent molecules. Features of the crystal structure account
for the deep color of crystals of azothiazole 6. We should note that although there are no asymmetric atoms in
the structure of azothiazole 6 and the molecules completely coincide with their mirror antipodes by virtue of the
planar conformation, the crystal structure is nevertheless chiral; the space group is P21. This circumstance
should determine the physical properties of crystals of azothiazole 6 characterized by third-order
609

tensors since all the components of these tensors should be nonzero due to the indicated symmetry. In particular,
non-zero components should be found for the nonlinear optical susceptibility tensor, which should give rise to
the optical properties of the crystals of azothiazole 6, for example, the generation of a second harmonic.
EXPERIMENTAL
1
The H NMR spectra were taken on a Varian Mercury BB 200 spectrometer at 200 MHz, while the
13C NMR spectra were taken on a Varian Mercury BB 400 spectrometer at 100 MHz using TMS as the internal
standard. The melting points of 3, 5, and 6 correspond to previously reported values [6].
A diffraction pattern for the X-ray diffraction crystallographic analysis was obtained for the
monocrystals on a Bruker-Nonius KappaCCD automatic diffractometer at room temperature. The crystal
structure was solved by a method developed at the Latvian Institute of Organic Synthesis [9]. The initial
R-factor of the model of the structure after the solution was 30%. Further refinement was carried out by the
full-matrix method of least squares anisotropically for the non-hydrogen atoms using the AREN program
package [10]. The positions of the hydrogen atoms were localized in the Fourier electron density difference map
and refined using the "rider" model. The crystallographic data for azothiazole 6 and refinement parameters for
the structure are given in Table 2. The complete crystallographic data set and diffraction data for crystals of
azothiazole 6 were deposited in the Cambridge Crystallographic Data Center (CCDC No. 725676).
1
2-Phenylazo-5-(3,4,6-trichloro-2,5-dihydroxyphenyl)thiazole (5). Mp >250°C (dec.) [6]. H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 7.66 (3H, m, H-3, H-4, H-5 C6H5); 7.96 (2H, m, H-2, H-6 C6H5); 8.18
13
(1H, s, H-4 thiazole); 9.94 (1H, s, OH); 10.13 (1H, s, OH). C NMR spectrum (DMSO-d6), δ, ppm: 118.69,
120.95, 122.28, 123.69, 123.94, 130.37, 132.54, 134.03, 144.37, 146.16, 146.23, 151.52, 176.52.
1
2-Phenylazo-5-(trichloro-1,4-benzoquinonyl)thiazole (6). Mp 166°C (dec.) [6]. H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 7.57 (3H, m, H-3, H-4, H-5 C6H5); 8.08 (2H, m, H-2, H-6 C6H5); 8.80 (1H, s,
H-4 thiazole).
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