New reactions of 4,5-disubstituted 1,2,3-thiadiazoles in the presence of NaH

1,4-Dithiafulvenes, 1,2,3-thiadiazolylalkylketones, 5-(2-aryl-1-phenylethenyl)-1,2,3-thiadiazole, 1,4-dialkyl-3,6-bis(phenylmethylidene)-2,5-dithiabicyclo[2.2.1]heptane, bis-2,4-(1,2,3-thiadiazol -5-yl)-alkenes and (6-benzyl-3,4-diphenyl-3,4-dihydro-2H-thiopyran-2-ylidene)(phenyl)-metha nethiol were formed as a result of transformations of 4,5-disubstituted-1,2,3-thiadiazoles containing an active methylene fragment


Results and Discussion
5][6] The yields of 2a-j were increased compared to the previously reported procedures by using a small excess of thionyl chloride in methylene chloride.5-Benzylthio-4-phenyl-1,2,3-thiadiazole 2k was prepared according to an earlier reported procedure. 5ompounds 2a and 2d both displayed unusual photochromic behavior.Freshly recrystallized samples of these compounds were colorless, but upon exposure to sunlight or UV irradiation they turned to a persistent pink-purple color.Dissolution of either form of the crystals produced apparently identical colorless solutions.Recrystallization of the colored crystals from organic solvents gave colorless crystals, which again upon exposure to irradiation turned into colored crystals.In an attempt to gain insight into the origin of this phenomenon, IR, UV investigation and X-ray structure determinations were carried out on each of the two forms of the crystals of 2a.However, the two structures were identical within experimental error, and hence the difference in color is not associated with different molecular dimensions.They crystallize in isomorphous space groups (P2 1 2 1 2 1 ) with two independent molecules in the asymmetric unit.The complex molecular packing includes some unusually short intermolecular S … N and C-H … N interactions, as shown in Figure 1.The UV and IR spectra were also identical for the crystals of both colors.In the preparation of 2i, when acetone was used to quench excess of thionyl chloride, byproduct 3 was formed probably through intermediate 9.The structure of compound 3 in solution was established with NMR data.In the 1 H NMR spectrum of 3 the signal at 6.84 ppm was easily assigned to H-6.For the unambiguous chemical shift assignment of the two methyl groups the NOE method was used.Irradiation of the H-6 resonance signal at 6.84 ppm (Figure 2, b) reveals one of the methyl groups at 2.39 ppm (4-CH 3 ) and the ortho protons of the phenyl ring ca.7.22 ppm.The mutual NOE enhancement effect was observed when the 4-CH 3 resonance signal at 2.39 ppm (Figure 2 The structure of 3 was confirmed by X-ray crystal structure determination.The crystals of 3 have a deep red color.Figure 4 shows a perspective view of the molecular structure, which confirms the atom connectivity, the stereochemistry about the exocyclic double bond and establishes the conformations of the side chains in the solid state.The dithiafulvene 4 was formed on reaction of 5-benzylthio-4-phenyl-1,2,3-thiadiazole (2k) with NaH.Compound 4 is well-known: 4 is readily formed (i) by base catalyzed decompositions of 1,2,3-thiadiazoles, 7 (ii) by treatment of 4-phenyl-1,2,3-thiadiazole with base, 8a,b and (iii) from other precursors.8c We believe that in our case the formation of dithiafulvene 4 proceeded by a preliminary proton intramolecular migration from methylene group to thiirene fragment (Scheme 2).The reaction was carried out in DMF in the presence of sodium hydride.
A reaction sequence similar to (ii) took place when DMF was used instead of an aldehyde.Thus, brief heating of thiadiazoles 2d,e,f in DMF with 3 equivalents of sodium hydride gave bis(1,2,3-thiadiazol-5-yl)alkanes 12a-d as mixtures of d,l and meso-forms (Scheme 3).
The formation of compounds 13a,b probably occurs via 12 as intermediates (Scheme 3).In the next step, double recyclization followed by dinitrogen elimination from the 1,2,3-thiadiazole ring and double migration of a hydrogen atom from a α-methylene fragment affords 3,6-di-(phenylmethylidene)-1,4-diethyl-2,5-dithiabicyclo[2.2.1]heptane 13b.Heating more strongly or keeping for a longer time in the presence of excess of NaH leads to deep seated degradation of 1,2,3-thiadiazoles; for example, thioamides 14a,b were obtained when 2c was stirred at room temperature for two days or 2f was heated in DMF with NaH.The two isomeric (meso-12a, and d,l-12b) 4,5-disubstituted thiadiazoles were characterized by one and two dimensional NMR techniques (DEPT, selective decoupling, COSY, HETCOR).The 1 H NMR spectra of 12a and 12b and the protons of 6´-CH 2 and 7-CH 2 groups are nonequivalent, and exhibit different chemical shifts.A useful assignment strategy to distinguish between protons of two types of methylene groups (6´-CH 2 and 7-CH 2 ) is on the basis of selective decoupling, and HETCOR experiments.The low field (multiplet centered at 3.02 ppm) was assigned to H-6.A representative example of HETCOR spectra is shown for 12a.The typical one bond correlation peaks are presented on the contour plot of HETCOR spectrum by dotted arrows (Figure 5).
The DEPT data indicate different forms of the carbon atoms in the aliphatic unit (6-CH 3 , 6´-CH 2 and 6-CH).The assignment of quaternary carbon atoms at 130.8 ppm ( ipso C), 157.3 ppm (C-5) and 160.3 ppm (C-4) were made by long-range heterocorrelation HETCOR-LR experiments; optimized for 8 Hz long-range J CH coupling.
Characterization of 13a as C 21 H 20 S 2 was achieved by high-resolution NMR techniques.The two-fold symmetry of 13a simplifies both the proton and carbon spectra and thus, only half of the molecule needs to be discussed.The 1 H NMR spectrum of 13a shows three types of singlet signals at 1.96, 2.26 and 6.45 ppm, which belong to CH 3 , 7-CH 2 and H-6a, respectively.The ratio of integral intensity in 13a is 5:1:1:3.The assignment of the ortho protons of the phenyl ring in 13a was carried out via the appropriate NOE experiments (see Figure 6).Unequivocal assignments of carbon chemical shifts were made on the basis of coupled 13 C NMR, HETCOR (the proton bearing carbon) and long-range correlation HETCOR-LR (to determine the chemical shifts of quaternary carbon atoms) experiments (Figure 7).The structure of compound 13 was unambiguously confirmed by single crystal X-ray analysis.Figure 8 shows a perspective view of the molecular structure and confirms the stereochemistry of the benzylidene groups.Another class of 1,2,3-thiadiazole transformations was observed when the methylene fragment of the substituent was in the 4-position of the 1,2,3-thiadiazole rings.Thus, heating of 4-benzyl-5-phenyl-1,2,3-thiadiazole 2g in DMF in the presence of sodium hydride led to 15 (Scheme 4).The structure of compound 15 was determined by single crystal X-ray analysis.Figure 9 shows a perspective view of the molecular structure, which establishes the overall structure of the molecule, along with the stereochemistry of the phenyl substituents and the exocyclic double bond.
The formation of compound 15 can be rationalized by nitrogen elimination followed by a migration of a hydrogen atom from the methylene fragment to the sulfur or carbon atom to form two intermediate fragments.The new C-C bond is formed after the 1,3-cycloaddition of the biradical to the allene.

Figure 1 .
Figure 1.Perspective view showing the short intermolecular S … N and C-H … N interactions (dotted lines) in the X-ray crystal structure of 2a.

Figure 4 .
Figure 4. Perspective view of the structure of 3.

Figure 8 .
Figure 8. Perspective view of the structure of 13a.