An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

Dialkyl 5,5'-dioxo-4,4'-bipyrazole-4,4'-dicarboxylates are readily obtained by the reaction of 5-hydroxypyrazole-4-carboxylates in refluxing thionyl chloride. The obtained diesters can be transformed into the corresponding 4,4'-bipyrazoles via alkaline hydrolysis and subsequent decarboxylation. Detailed NMR spectroscopic investigations (1H, 13C, 15N) were undertaken with all products prepared. Moreover, the structure of a representative 5,5'-dioxo-4,4'-bipyrazole-4,4'-dicarboxylate was confirmed by X-ray crystal structure analysis.


Results and Discussion
Chemistry However, the attempted reaction of ester 1a (R 1 = Ph, R 2 = H, R = Et) with POCl 3 left the starting material untouched, similarly by treatment of 1a with oxalyl chloride no conversion occurred (Scheme 2). In contrast, treatment of 1a with excessive thionyl chloride at reflux temperature resulted in a defined reaction product which, however, could not be the desired 5-chloro derivative 2a according to -amongst others -a much too large chemical shift of pyrazole C5 (δ 165.6 ppm) compared to the expected one (δ 131.3 ppm) [15]. Moreover, the OCH 2 protons revealed to be of diastereotopic character which hints to the presence of a chiral center in the molecule (Figure 1), while the molecular weight obtained by HRMS measurement ([M + Na] + 485.1432) testified about the possible formation of a dimeric structure.
Lastly, by X-ray crystal structure analysis the obtained product could be determined as the dimeric structure 3a (Scheme 2, Figure 2). In addition, HRMS and elemental analysis con-  firmed the molecular formula. The non-equivalence of the OCH 2 protons of the ester functions can be smoothly explained by the presence of an asymmetric carbon atom at pyrazole C4/C4'. As the NMR spectra displayed a single set of signals, regarding the stereochemistry a racemic mixture or the mesoform came into consideration.
The single crystal X-ray analysis disclosed that the molecule of the newly obtained compound 3a consists of two pyrazolone residues, which are directly connected to each other by a single covalent carbon-carbon bond between the asymmetric sp 3hybridized C4 and C4' carbon atoms to form a species with relative (4R*,4'R*)-configuration (  each other by weak intermolecular hydrogen bonds (C-H···O 2.523 Å, 130.64°, Figure 3).
In the following, related 5-hydroxypyrazol-4-carboxylates 1b-i were subjected to the same reaction conditions (refluxing SOCl 2 ) and in all cases the corresponding dimers of type 3 were obtained in moderate to good yields (Scheme 3).
In order to check if these dimerization reactions also occur with other 5-hydroxypyrazoles carrying a C=O function at pyrazole C4 we subjected ketone 4 and hydrazide 5 to the same reaction conditions. In both cases, a plethora of unidentified products resulted (Scheme 4). In contrast, with aldehyde 6 a reaction product could be isolated in moderate yield, which can be assigned to structure 7 considering NMR data and mass spectra (Scheme 4).
Moreover, we investigated the reaction of 1a with SO 2 Cl 2 . Here, two reaction products -8 and 9 -were isolated, whereas in both cases chlorination not only at the pyrazole C4 but also in the 4-position of the phenyl ring took place (Scheme 5). The reaction mechanism for the transformation 1 → 3 is unclear. Dimerization by air oxidation can be ruled out as performing the reaction under N 2 atmosphere provided the same result. It should be mentioned that for the oxovanadium(V)mediated dimerization of 4-aroyl-5-hydroxypyrazoles mentioned above a radical mechanism was postulated [32]. However, in Scheme 6 we propose a hypothetical mechanism comprising a redox cyclization of an intermediate di(pyrazolyl) sulfite under elimination of sulfur monoxide.
Finally, it was shown by means of some selected examples, that compounds of type 3 can be converted into the corresponding bipyrazoles 10 upon alkaline hydrolysis and subsequent decarboxylation (Scheme 7). According to the NMR spectra, compounds 10 are obviously present as 5-hydroxypyrazoles due to the absence of a proton attached to pyrazole C4.

NMR spectroscopic investigation
In Supporting Information File 1 the NMR spectroscopic data of all compounds treated within this study are indicated. Full and unambiguous assignment of 1 H, 13 C and nearly all 15 N NMR resonances was achieved by combining standard NMR techniques [33], such as fully 1 H-coupled 13 C NMR spectra, APT, gs-HSQC, gs-HMBC, gs-HSQC-TOCSY, COSY, TOCSY and NOESY spectroscopy. Figure 4 shows the thus assigned 1 H, 13 C and 15 N NMR chemical shifts for model compound 3a.

Supporting Information
Supporting Information File 1 Experimental details and compound characterization.