Chemistry of polyhalogenated nitrobutadienes, 4: reactions of mono-, bis-, and tris(4-tolylthio) derivatives of 2-nitroperchloro-1,3-butadiene with α,β -bifunctional nucleophiles

The reaction of 1-(4-tolylthio)-, 1,1-bis(4-tolylthio)-, or 1,1,3-tris(4 - tolylthio)perchloro-2-nitro-1,3-butadiene with α,β -bifunctionalized ethanes such as N , N -, N , O ,-, N , S -, O , S -, S , S -, or O , O - bisnucleophiles leads to both, highly functionalized 2-(1-nitroallylidene) derivatives of imidazolidine, oxazolidine, thiazolidine, [1,3]oxathiolane, or [1,3]dithiolane, respectively, and to the open chain, next higher thiolated buta-1,3-diene. The product distribution is highly sensitive to modifications of the reaction conditions: apart from changes of molar ratios of substrates and reagents the reaction temperature plays an important role. Thus, increase of the reaction temperature favours formation of the 1,3-heterocyclic ring. In all cases, extensive spectroscopic investigations have been performed and, in the case of the [1,3]oxathiolane also an X-ray analysis.


Introduction
Due to their stepped reactivity in S N reactions, nitro-substituted polyhalogeno-1,3-butadienes have proven to be valuable synthetic precursors for a variety of polyfunctionalized bioactive heterocycles. 1,2Often times, the building block of choice is 2-nitroperchloro-1,3-butadiene (1)  which is easily accessible by the introduction of an activating and directing nitro group into 2Hpentachloro-1,3-butadiene.Synthetic use of 1 opens access to a quite diverse chemistry, the documentation of which has been started by our group recently. 1The preferred primary reaction center of 1 is the activated terminal carbon atom C-1 of the nitrodichlorovinyl moiety.This carbon atom allows for an attack by different nucleophiles in S N Vin processes.Under harsher conditions the internal carbon atom, C-3, is additionally open to the attack of nucleophiles.Therefore, in this fourth paper of our series we present the results of various reactions of 1-(4tolylthio)-1,3,4,4-tetrachloro-, 1,1-bis(4-tolylthio)-3,4,4-trichloro-, and also 1,1,3-tris(4tolylthio)-4,4-dichloro-2-nitro-1,3-butadiene with aliphatic N,N-, N,O,-, N,S-, O,S-, S,S-, or O,Obisnucleophiles as well as some additional conversions of the resulting compounds.

Scheme 1
The subsequent vinylic substitution of the monothio compound 3 by means of 1,2-ethylenediamine (MeOH, 0°C,1 h; 3:amine = 1:2) gives dithio compound 4 (48%) as well as 2-(2,3,3-trichloro-1-nitroallylidene)imidazolidine (5) (35% yield).The latter reaction can be classified as a nucleophilic exchange reaction which, starting from the monothio derivative 3, leads to the 1,1-dithio compound 4 and, in addition, the sulfur-free imidazolidine 5. Arylthiols are known to be both good nucleophiles as well as good leaving groups.Successive, regioselective reaction of imidazolidine 5 with thiol 2 (MeONa, MeOH, 30-35°C, 6 h) provides the C-3 thio-substituted imidazolidine 6 in very good yield (90%).As a side-product, di(4tolyl)disulfide (7) was obtained (5%) also.This oxidative coupling in the presence of air is quite common for thermal conversions or nucleophilic vinylic substitutions with aryl thiols. 3At higher temperatures (e.g.methanol reflux) and with an excess of ethylenediamine, the direct conversion of the mononitrodiene 3 into the imidazolidine 6 was feasible, but the yield dropped down to 50% and, unfortunately, the undesired disulfide 7 then was produced in 15% yield (Scheme 2).The first mentioned imidazolidine 5 is speculated to be a reaction intermediate, the trichlorovinyl group of which is attacked by an in situ formed arenethiolate anion.Apparently, this pathway ends up with the release of a chloride anion, which for its part forms the corresponding hydrochloride with excess ethylenediamine.

Discussion of the NMR and IR data for compounds 1, 3, 4 and 8
First of all, it is worthy of note that our spectroscopic data are in accordance with those reported by Ibis et al. 2a but, apparently, the reported tris(4-tolylthio)dichloronitro-1,3-butadiene is not a 1,1,4-substituted, but a 1,1,3-tris(4-tolylthio) regioisomer instead.This indication was proven by X-ray analysis and, in addition, by an independent synthesis of imidazolidine 6 starting from the tris(thio)nitrodiene 8.
The nmr shifts of the C-1 carbon atoms of compounds 3, 4, and 8 (the atom numbering of these non-heterocyclic compounds follows the example in Scheme 1) appear relatively downfield around 160 ppm, whereas the NO 2 -bearing carbon atoms C-2 each show their resonance, a broadened less intense peak, between 138 and 141 ppm.In accordance with the assignment of carbon nmr data for similar nitrobutadienes, 5 the individual C-3 and C-4 carbons each provide chemical shift values around 122 ppm and 129 ppm, respectively.In addition, the 13 C-NMR shifts within the thioaryl units of 3, 4, and 8 have been assigned by appropriate incremental shifts for substituted benzene derivatives. 6The proton nmr data show typical ppm values and splitting patterns (AA'BB'-system of the aromatic protons within the range 6.63-7.60 ppm and 2.30-2.43ppm for the methyl singlets, respectively).Furthermore, some characteristic bands in the IR spectra of compound 3, 4, and 8 should be mentioned: The C=C stretching band is observed within the range 1572-1606 cm -1 , and the NO 2 groups range from 1512 to 1531 cm -1 (asymmetric stretching) and from 1310 to 1321 cm -1 (symmetric stretching).An IR band around 510 cm -1 is assumed to stem from the C-S vibration, even though somewhat higher values can be found in the literature. 7n the course of the vinylic substitutions, the reaction of the monothio derivative 3 with ethanolamine or N,N'-diphenyl-ethylenediamine in methanol afforded the bis(4-tolylthio)diene 4 (45-50%) and the corresponding heterocyclic compounds, i.e. the oxazolidine 9 or the imidazolidine 10, respectively, in 20 to 25% chemical yield.The disproportionation of the bis(arylthio)nitrodiene 4, effected by one of the bisnucleophiles mentioned above at room temperature, revealed the tris(arylthio)butadiene 8 (43-47%), the disulfide 7 (3-5%), and the heterocycles 11 or 12 (12-15%).In analogy to the reaction of the imidazolidine 6 with 4tolylthiol (2), the pre-formed heterocycle 9 was reacted with 2, whereas 10 additionally was combined with the unsubstituted benzenethiol in sodium methoxide solution at slightly elevated temperature.Even though the resulting oxazolidine derivative 11 was obtained in 50% yield, the imidazolidines 12 and 13 were accessible in 90-93% yield (with traces of the side product 7).Some further attempts to convert the tris(4-tolylthio)butadiene 8 to the oxazolidine 11 or to the imidazolidine 12 with ethanolamine or N,N'-diphenyl-ethylenediamine, respectively, were unsuccessful.In detail, at room temperature no reaction occurs, whereas at elevated temperatures (60-65°C) an inseparable complex mixture of products was obtained.Aside from steric reasons (i.e. the presence of three aromatic rings has to be taken into account), especially in the case of ethanolamine, this result was not unexpected due to the fact that the nucleophilic oxygen of ethanolamine represents a harder nucleophilic center (following Pearson´s concept 8 ) than the nitrogen of the amino group.The former should be able to initiate the fragmentation of the double bond of the C(NO 2 )=C(S-)S-unit, as is known from the alcoholysis of 2-nitroperchloro-1,3-butadiene (1), which leads to 1,1,2-trichloro-3-nitro-1-propene as well as to the corresponding esters of 2-nitro-3,4,4-trichlorocrotonic acid. 9Additionally, with the imidazolines 12 and 13 in hand, some subsequent synthetic steps appeared to be useful.Thereby, the oxidation of the sulfur in 12 by means of 77% m-chloroperbenzoic acid was performed (CHCl 3 , r.t., 30 h), providing the sulfone 14 in 90% yield.In addition, the saponification of the internal chloro substituent of the trichlorvinyl group in 10 with aqueous dimethylsulfoxide at 80°C gave the synthetically interesting nitrobutenone 15 in 65% yield (Scheme 4).

Discussion of the NMR data for compounds 5, 6, 9-14, and 16-21
The particular carbon atoms in the 2-position of these heterocyclic compounds (for atom numbering refer to compound 6 in Scheme 2) show their resonance in a range between 155 and 178 ppm, depending on the kind of heteroatoms, i.e. 155 to 159 ppm (N-C-N), around 165 ppm (N-C-O), 168 ppm (N-C-S), 171 ppm (S-C-S), and 177 ppm (S-C-O) ppm.The ppm value for the broad resonance of the C-6 carbon atom shows by far the highest range: 102.6 to 105.8 ppm (imidazolidines and oxazolidines), and 113.1 to 130.1 ppm (thiazolidines, oxathiolanes, and dithiolanes).Moreover, apart from the sulfone 14 and nitrobutenone 15, the 13 C-NMR peaks of the C-7 and C-8 carbon atoms of 5, 6, 9-14, and 9-21 were found within 117.0-125.8ppm (C-8), and 125.7-131.0ppm (C-7), respectively.Consequently, the C-7 and C-8 carbon atoms of the sulfone 14 resonate much deeper, i.e. at 136.9 and 137.4 ppm.Among the expected appearance of the proton nmr spectra of 6, 11, 12, 14, and 19-21, especially as AA'BB'-systems, the NH group of imidazolidine 5 exhibits a proton signal around 8.5 ppm.This chemical shift, typical for nitroenamines 4,10 is a result of the intramolecular hydrogen bonding shown in Fig. 2. In addition, both of the amino groups in 5 are spectroscopically identical on account of the tautomerism (see Fig. 2).After introduction of the bulky 4-tolylthio substituent, the former free rotation around the partial C(2)-C(6) single bond becomes a hindered one.Thus, two separate proton nmr signals of the amino groups are observed in 6.The associated NH proton appears at 8.4 ppm, whereas the unassociated NH group resonates at 5.7 ppm (in CDCl 3 ).

Experimental Section
General Procedures.Melting points were measured on a Büchi 520 apparatus and were uncorrected.NMR spectra were obtained on a BRUKER Avance with 400 MHz proton frequency. 1H-NMR spectra in CDCl 3 were referenced to tetramethylsilane (TMS) as internal standard at 0.0 ppm; 13 C-NMR spectra refer to the solvent signal center at 77.0 ppm (CDCl 3 ).In case of DMSO-d 6 , the solvent peak was set to 2.50 ppm ( 1 H) and 39.70 ppm ( 13 C), respectively.Coupling constants are given in Hertz.IR spectra were obtained on a BRUKER 'Vector 22' FT IR as film between NaCl plates or as KBr pellet.UV/Vis spectra were measured on a HP 8452a (Hewlett-Packard) and refer to ethanol as solvent and a concentration of 10 -4 mol/l.Mass spectra were recorded on a Hewlett Packard 'MS 5989B' with direct inlet.All masses of chlorine containing molecules or fragments refer to the isotope 35 Cl.High-resolution mass spectra were measured with a Bruker Daltonik 'APEX IV' 7 T fourier transform ion cyclotron resonance mass spectrometer with electrospray ionisation at Institute of Organic Chemistry, University of Göttingen.Elemental analyses were performed by the Institute of Pharmaceutical Chemistry, Braunschweig Technical University.TLC analyses were carried out on Merck-plates coated with silica gel (60 F 254).Silica gel 60 was used also for column chromatography.
The reactions of monothiodiene 3 with ethanolamine (to give 55% of bisthiodiene 4) and 1,2ethylenediamine (50% of 4) have been performed in accordance with the general procedure 1.In the latter case, the reaction required 3 h at room temperature.