Direct Exchange of Oxygen and Selenium Atoms in the 1,2,5-Oxadiazoles and 1,2,5-Selenadiazoles by Action of Sulfur Monochloride

A short synthetic approach to fused 1,2,5-thiadiazoles from the corresponding 1,2,5-oxadiazoles and 1,2,5-selenadiazoles has been developed. Mono- and bis(1,2,5-thiadiazoles) were selectively obtained in high yields. The pathways for these novel reactions were discussed.


Introduction
1,2,5-Thiadiazoles and particularly their benzo-fused derivatives have been known for many years, and their synthesis and applications in various branches of technology and medicine were extensively investigated and reviewed [1][2][3][4][5]. Recently, they were found to be an efficient electron acceptor and were used as the building blocks of many actual or potential molecule-based functional materials for organic electronics and spintronics [6][7][8][9][10][11][12]. Although methods for the preparation of fused 1,2,5-thiadiazoles are numerous and well elaborated [2,3,5], there is still a lack of suitable preparative approaches to many interesting derivatives containing electron-deficient heterocycles or electron-withdrawing groups.
A few years ago 3,4-diamino-1,2,5-oxadiazole 1 was found to react with sulfur monochloride and pyridine in acetonitrile and gave, unexpectedly, [1,2,5]thiadiazolo [3,4-c] [1,2,5]thiadiazole 2 in high OPEN ACCESS yield (Scheme 1) [10]. The main feature of this transformation is an exchange of the oxygen atom in the 1,2,5-oxadiazole ring with a sulfur atom in the reaction with sulfur monochloride. To the best of our knowledge, this is the first example of this unusual reaction. Later on, it was shown that another oxadiazole derivative, 4-amino-3-nitro-1,2,5-oxadiazole 3, can undergo a similar transformation with S2Cl2 in lower yield [13]. Recently, it was discovered that under similar conditions, (5Z,6Z)- [1,2,5]oxadiazolo [3,4-b]pyrazine-5,6(4H,7H)-dione dioxime 4 gave tricyclic bis([1,2,5]thiadiazolo)-[3,4-b;3′,4′-e]pyrazine 5 in moderate yield (Scheme 2). In that case, three reactions occurred: exchange of an oxygen atom in a 1,2,5-oxadiazole ring by a sulfur atom, formation of thiadiazole ring from dioxime, and aromatization of a piperazine ring [14]. A specific feature of sulfur monochloride (S2Cl2) is its diverse reactivity [15][16][17][18]. The most useful property of this compound is its sulfurating ability. Apart from this, S2Cl2 is a strong chlorinating agent, but it is rarely used since there are many other chlorinating agents that afford higher yields of the reaction products. The oxidative ability of S2Cl2 has been investigated to a much lower extent because the products of formal oxidation reactions are formed, as a rule, in a course of complex multistage processes involving chlorination, dehydrochlorination, sulfuration, etc. A direct exchange of a chalcogen atom with a sulfur atom in the reaction with sulfur monochloride in chalcogen-nitrogen heterocycles has not been discovered before our works [10,13]. To the best of our knowledge, the only formal analogy of this exchange is the classical Yuryev reaction performed under very drastic conditions [19][20][21]. However, the reaction pathways seem to be very different and its scope is very limited to heterocycles with one heteroatom, and high yields were achieved by using furan as a starting material; vigorous conditions of this method did not allow its spread for compounds with labile groups.
Tricycle 5 can be obtained also from diamine derivative 9 by treatment with S2Cl2 and pyridine in boiling MeCN (Scheme 5). In that case, two processes take place simultaneously-the formation of the thiadiazole ring from the diamine moiety and the dehydration of dihydropiperazine into the aromatic pyrazine ring, presumably by action of sulfur monochloride. Dehydration of dihydropiperazine to a pyrazine ring is quite a rare process and it was investigated in detail for bis(1,2,5-thiadiazole) derivative 8. It was found that the treatment with a rank of oxidizers usually used for similar processes-bromine, DDQ, PhI(OAc)2 and its perfluoro analog PhI(O(C(O)CF3))2 in various solvents (CHCl3, THF, ether, MeCN)-gave no reaction in most cases, and in some it led to the decomposition of starting material. Aromatic bis-1,2,5-thidiazolopyrazine 5 has been obtained in the reaction of 8 with sulfuryl chloride, and it was found that to get a high yield of compound 5, it is necessary to employ eight equivalents of oxidant and hours-long boiling.
The described procedures provide a new synthetic pathway to fused 1,2,5-thiadiazoles from corresponding oxadiazoles. The key steps may be explained by the sulfurization of the tautomeric form 10 of the tricycle 6 with sulfur monochloride in the presence of the base to give chlorodithio derivative 11, followed by the elimination of hydrogen chloride with the formation of N-thiosulfinylamine 12 (Scheme 6). Further cyclization of compound 12 into 1,2,5-thiadiazole 7 via cycloaddition/ retrocycloaddition with the extrusion of sulfur monoxide (SO), which is thermodynamically unstable and decomposes very rapidly [22], may occur. A similar formation of the 1,2,5-thiadiazole ring from N-thiosulfinylamine and nitro groups has recently been proposed [13]. This reaction could then be repeated to give bis(1,2,5-thiadiazole) 8, which may oxidize with the formation of aromatic tricycle 5.
The most important results are summarized in Table 2.

Scheme 7.
Reactions of [1,2,5]selenadiazolo [3,4-b]pyrazines 13-15 with sulfur monochloride. In all cases, the formation of the characteristic red amorphous precipitate of elemental selenium was indicated. In the case of 16, this precipitate was isolated in practically quantitative yield and its structure was confirmed by mass-spectrometry and elemental analysis.
We attempted to extend this reaction to benzo-fused and monocyclic 1,2,5-selenadiazoles. It was found that 2,1,3-benzoselenadiazole and 3,4-diphenyl-1,2,5-selenadiazole did not react with sulfur monochloride in organic solvents under forcing conditions (refluxing in acetonitrile or heating in DMF at 100 °C for 10 h) and were recovered from the reaction mixtures in practically quantitative yields.
To compare the reactivity of 1,2,5-oxadiazoles and 1,2,5-selenadiazoles in the reaction with sulfur monochloride, it should be noted that in both cases a fused nitrogen-containing heterocycle is needed for the successful exchange of oxygen or selenium atoms to sulfur. The most plausible mechanism of the conversion of 1,2,5-selenadiazoles into 1,2,5-thiadiazoles is shown in Scheme 9. The key steps may include the sulfurization of the selenadiazole ring with sulfur monochloride to give chlorodithio derivative 24, followed by the recyclization of the selenadiazole ring and the elimination of sulfur dichloride with the formation of 1,2,5-selenadiazolo-N-selenide 25 (Scheme 9). Further extrusion of elemental selenium, which is precipitated from the reaction mixture, affords the final 1,2,5-thiadiazole.
The method described here supplemented and enhanced the possibilities for the synthesis of fused 1,2,5-thiadiazoles.

General Information
Elemental analyses for C, H, and N were performed with Perkin Elmer 2400 Elemental Analyser (Perkin Elmer, Waltham, MA, USA). Melting points were determined on a Boetius hot-stage apparatus and are uncorrected. 1 H-(300.1 MHz) and 13 C-(75.5 MHz) NMR spectra were taken for CDCl3 solutions (unless otherwise indicated) with a Bruker AM-300 (Bruker AXS Handheld Inc., Kennewick, WA, USA) and referred to tetramethylsilane ( 1 H and 13 C), J values are given in Hz.
MS spectra (EI, 70 eV) were obtained with a Finnigan MAT INCOS 50 (Hazlet, NJ, USA). High-resolution MS spectra were measured on a Bruker micrOTOF II instrument (Bruker Daltonik Gmbh, Bremen, Germany) using electrospray ionization (ESI). The measurement was operated in a positive ion mode (interface capillary voltage −4500 V) or in a negative ion mode (3200 V); mass range was from m/z 50 to m/z 3000 Da; external or internal calibration was done with Electrospray Calibrant Solution (Fluka). A syringe injection was used for solutions in acetonitrile, methanol, or water (flow rate 3 µL·min −1 ). Nitrogen was applied as a dry gas; interface temperature was set at 180 °C.

General Procedure for the Reaction of 1,2,5-Oxadiazoles with S2Cl2 and Pyridine in Acetonitrile
Sulfur monochloride (quantity, see Table 1) was added dropwise to a stirred suspension of oxadiazole 6-9 (1.0 mmol) and pyridine (quantity, see Table 1) in dry acetonitrile (10 mL) under argon at −25 °C. The mixture was stirred at room temperature or heated at the temperature and for the time specified in