Benzo-and naphthoimidazoxadiazolediene, naphthobisthiazole as well as naphthothiazine derivatives from 1-acylthiosemicarbazides

1-Acylthiosemicarbazides 1a-d reacted with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone ( 2a ), 2,3,5,6-tetrachloro-1,4-benzoquinone ( 2b ), 2,3-dichloro-1,4-naphthoquinone ( 3a ) and 2,3-dicyano-1,4-naphthoquinone ( 3b ) in ethyl acetate with admission of air to form benzo-and naphtho-imidazoxadiazoles (5, 6, 11) , naphthobisthiazoles (12a-d) , naphthothiadiazines (13a-d) as well as 2,3,7,8-tetrachlorothianthrene-1,4,6,9-tetraone (7) . Rationales for the observed conversions are presented.


Results and Discussion
Mixing of two-fold molar amounts of 2a with one mole each of the donors 1a-d in ethyl acetate with admission of air gives a blue colour (λ max = 573-591 nm).This colour changes gradually to brown with the formation of a solid product.This behaviour is explained as being due to initial formation of an unstable charge-transfer complex (CTC) followed by a chemical reaction which yields substituted benzimidazoxadiazole 5a-d via the reaction of dihydrobenzoquinone (2a-H 2 ) with 4 and elimination one molecule of HCN and another of H 2 O (Scheme 1).The structures of the well known compounds 4a-c were confirmed on the basis of spectral data and mixed melting points.The structural assignments for the benzimidazoxadiazole derivatives 5a-d are based on the following spectral data: the IR spectrum of 5a showed characteristic absorption for the hydroxyl group at ν 3440 cm -1 and at 2220 cm -1 for the cyano group.The 1 H-NMR spectrum showed a broad signal at 9.53 ppm due to the OH in addition to the methyl group at 2.33 ppm.The decoupled 13 C-NMR spectrum showed signals at δ 164.82, 156.22 and 150.71 for C-2, C-9a and C-8a, respectively.Also, the 13 C-NMR clearly indicates the presence of one cyano group at 118.77 ppm beside the aromatic carbons.
The molecular formulae for 5a-d (Scheme 1) are supported by elemental analyses and mass spectra, which gave the expected molecular ion peaks.The semi-micropreparative scale reaction of 1a with 2a gave 5a, as established from the comparison of its IR spectrum and mp with those of an authentic sample.In addition, small quantities of numerous coloured, unidentifiable byproducts were observed.

Scheme 2
The IR spectrum of 6b showed a sharp band at 1695 cm -1 for the carbonyl group of the quinone system.The 1 H-NMR spectrum revealed a multiplet at 7.19-7.66ppm, which is characteristic of phenyl protons.The 13 C-NMR spectrum showed the characteristic absorption signals of the carbonyl carbon atoms of 2b at 170.72 and 171.83 22 .Other signals were observed in the 13 C-NMR of 6b, clearly indicating the presence of C=N, N=C-O, Cl-C=C=Cl groups (experimental part).The formation of 6b was further confirmed by mass spectrometry.Besides the molecular ion at 331/335, the characteristic fragment ion patterns of substituted dichloro compounds were observed 23 .
By mixing equimolar amounts of 1-acylthiosemicarbazides 1a-d and 3a in ethyl acetate the colour of the reaction mixture remains unchanged.Obviously, there is no donor-acceptor interaction between these two molecules, which is mainly due to the low electron affinity of 3a compared with 2b 24 .Heating of this mixture for 5 hours and chromatographic separation of the residue after concentration gave numerous coloured zones, from which naphthoimidazoxadiazoles 11a-d and naphthobisthiazoles 12a-d could be isolated (Scheme 4).
The structures of 11a-d were delineated from their spectroscopic properties and gross compositions.The major products 12a-d were found to be formed from one molecule of 3a-H 2 and two molecules of 1a-d by loss of two molecules of H 2 O and HCl.
The IR spectrum of 12d showed absorption characteristic of NH groups at 3385, 3225 cm -1 and a strong carbonyl group absorption at 1670 cm -1 .The 1 H-NMR spectrum of 12d clearly indicates the presence of two different broad signals centered at 10.65 and 11.17 ppm due to thiazole-NH and amide-NH, respectively.In addition, the benzylic-CH 2 as well as aromatic protons were observed (see experimental part).The 13 C-NMR of 12d showed a carbonyl signal at δ C = 171.48corresponding to the amide group.Also, the 13 C-NMR clearly indicates the presence of signals at 52.28 and 163.26 due to benzylic-CH 2 and thiazole-C 2 , respectively.The elemental analysis of 12d suggested a gross formula C 28 H 20 Br 2 N 6 O 2 S 2 and this was confirmed by the mass spectrum, which exhibited the molecular ion at m/z 698/694 (17 %).It should be noted also that the mass spectra of compounds 12a-d show the loss of an acyl group from the molecular ions.
In contrast to the situation with 3a, on addition of 1a-d to 3b, the initial formation of CT complexes (λ max = 523-532 nm) is followed by the formation of naphthothiazine derivatives 13ad in addition to oxadiazoles 4a-d (Scheme 5).For compound 13b, the gross formula C 20 H 13 N 5 O 2 S is supported by mass spectroscopy, which clearly demonstrates the loss of a benzoyl group.The 13 C NMR spectrum reveals the absence of the C=S signal and the presence of an amide C=O signal (171.56) and only one CN resonance (118.11ppm).In addition to an OH group, both a NH 2 (δ H = 7.12 ppm) and a low field amide-NH (δ H = 11.15ppm) are present.The IR spectrum of 13b showed bands at 3445, 3370-3250, 2220 and 1675 cm -1 due to OH, (NH and NH 2 ), CN and amide C=O groups, respectively.

Conclusions
Novel and interesting structures are presented here from the reactions between the electron donor 1-acylthiosemicarbazides 1a-d and electron acceptors; benzo-as well as naphthoquinones 2a,b and 3a,b.In a fairly complex, multistep process, three interesting kinds of fused heterocyclic compounds (benzo-and naphthoimidazoxadiazoles, naphthobisthiazole and naphthothiazine derivatives) are formed, in addition to the oxadiazole ring.Thus, benzo-and naphthoquinones may act either as mediators or as building blocks in heterocyclization of acylthiosemicarbazides.The results reported also supplement the chemistry of nucleophilic substitution of halogenated pquinones, which continues to be of interest for the synthesis of many heterocycles.

Experimental Section
General Procedures: The uncorrected melting points were determined on a Gallenkamp melting point apparatus, IR spectra were recorded using KBr disks on Shimadzu 408 or Bruker Vector 22 FT-IR instruments. 1 H 300 MHz and 13 C-NMR 75 MHz spectra were recorded on a Bruker WM300 instrument, 500 MHz 1 H and 125 MHz 13 C-NMR spectra on a Bruker DRX 500 spectrometer.Chemical shifts are expresses as δ [ppm] with reference to tetramethylsilane as an internal standard, s = singlet d = doublet, m = multiplet.The 13 C signals were assigned on the basis of DEPT 135/90 spectra.The mass spectra (70 ev, electron impact mode) were recorded on an AMD 604 instrument.The UV-VIS spectra were recorded on a Perkin-Elmer Lambda 2 spectrophotometer.Combustion analysis was carried out at the Microanalytical center, Cairo University, Egypt.Preparative layer chromatography (plc) was carried out using air dried 1.0 mm thick layers of a slurry of silica gel (Merck PF 254 ) applied on 48 cm wide and 20 cm high glass plates using cyclohexane/ ethyl acetate as developing solvent.Zones were detected by their colour or by quenching of indicator fluorescence upon exposure to 254 nm light and extracted out with acetone.Materials: 1-Acylthiosemicarbazides 1a-c were prepared according to the literature [25][26][27] .The 1 H-NMR spectral data of 1-acetylthiosemicarbazide (1a) 25 , 1-benzoylthiosemicarbazide (1b) 26 , and 1-(4-hydroxyphenyl)thiosemicarbazide (1c) 27 were in full accord with the published data.

Reaction of 1-acylthiosemicarbazides 1a-d with 2b
To a stirred solution of 492 mg (2 mmmols) of 2b in 30 ml of dry ethyl acetate, were added acylthiosemicarbazides 1a-d (1 mmol) in 15 ml dry ethyl acetate dropwise at room temperature.The colour of the reaction mixture changed gradually from reddish brown to pale blue.The mixture was stirred for another 72 h and then filtered off.The blue precipitate which contained compound 7 20 was washed with cold ethyl acetate.The filtrate was concentrated and the residue was then separated by preparative layer chromatography (plc) using a suitable eluent (cyclohexane/ ethyl acetate, 5:1 for the reaction of 2b with 1a and 1d; 3:1 for the reaction of 2b with 1b and 1c) to give numerous coloured zones, two of which (with high intensity) were removed and extracted.The faster migrating one, R f = 0.146, contained the oxadiazoles 4a-d, and the second zone, R f = 0.096 (characterized by its green colour) contained benzimidazoxadiazolediones 6a-d.Extraction of the zones with acetone, and concentration, gave a residue which was rechromatographed to separate the pure compounds.