4-Alkyl(aryl)-3-amino-1,2,5-thiadiazole 1,1-dioxides

Two methods have been developed for the synthesis of 3-amino-1,2,5-thiadiazole 1,1-dioxides; one leads to 4-alkyl derivatives, the other to 4-aryl analogs.     

Synthesis,structure, and oxidation of 3,4-dihydro-1,2,5-benzotrithiepins

Stable benzene-fused polysulfide compounds, 3,4-dihydro-1,2,5-benzotrithiepins ( 1a-c ), have been prepared, and the structure of 1a has been determined by X-ray crystallographic analysis. While the electrophilic oxidation of compounds 1 with m-chloroperbenzoic acid gave the corresponding 3,4-dihydro-1,2,5-benzotrithiepin 5-oxides ( 2 ) in moderate yields, the oxidation of 1 with N-bromosuccinimide afforded a mixture of 5-oxides 2 , unexpected, inseparable 3,4-dihydro-1,2,5-benzotrithiepin 2,2-dioxides ( 3 ), and 3,4-dihydro-1,2,5-benzotrithiepin 1,1-dioxides ( 4 ). Semiempirical PM3 calculations were carried out, and the computed HOMO of 1a suggested a significant favoring of electrophilic reactions at the sulfur atom at the 5-position. The treatment of 5-oxides 2 with acetyl bromide or oxalyl dibromide as halogenating reagents gave 2,2-dioxides 3 and 1,1-dioxides 4 , suggesting that an intramolecular halogen transfer from the 5-position (sulfide moiety) to the 1- and 2-positions (disulfide moiety) took place in the reactions.     

1,2,5]Thiadiazolo[3,4-c][1,2,5]thiadiazolidyl: a long-lived radical anion and its stable salts

[1,2,5]Thiadiazolo[3,4-c][1,2,5]thiadiazole (1) is synthesized in 62% yield by fluoride ion-induced condensation of 3,4-difluoro-1,2,5-thiadiazole with (Me(3)SiN=)(2)S. The reversible electrochemical reduction of 1 leads to the long-lived [1,2,5]thiadiazolo[3,4-c][1,2,5]thiadiazolidyl radical anion (2) and further to the dianion (3). The radical anion 2 is also obtained by the chemical reduction of the precursor 1 with t-BuOK in MeCN. The radical anion 2 is characterized by ESR spectroscopy in solution and in the crystalline state. The stable salts [K(18-crown-6)][2] and [K(18-crown-6)][2].MeCN (8 and 9, respectively) are isolated from the spontaneous decomposition of the [K(18-crown-6)][PhXNSN] (6, X = S; 7, X = Se) salts in MeCN solution followed by XRD characterization. The radical anion 2 acts as a bridging ligand in 8 and as chelating ligand in 9. The structural changes observed by XRD in going from 1 to 2 are explained by means of DFT/(U)B3LYP/6-311+G calculations.     

Interaction of 1,2,5-chalcogenadiazole derivatives with thiophenolate: hypercoordination with formation of interchalcogen bond versus reduction to radical anion

According to the DFT calculations, [1,2,5]thiadiazolo[3,4-c][1,2,5]thiadiazole (4), [1,2,5]selenadiazolo[3,4-c][1,2,5]thiadiazole (5), 3,4-dicyano-1,2,5-thiadiazole (6), and 3,4-dicyano-1,2,5-selenadiazole (7) have nearly the same positive electron affinity (EA). Under the CV conditions they readily produce long-lived π-delocalized radical anions (π-RAs) characterized by EPR. Whereas 4 and 5 were chemically reduced into the π-RAs with thiophenolate (PhS(-)), 6 did not react and 7 formed a product of hypercoordination at the Se center (9) isolated in the form of the thermally stable salt [K(18-crown-6)][9] (10). The latter type of reactivity has never been observed previously for any 1,2,5-chalcogenadiazole derivatives. The X-ray structure of salt 10 revealed that the Se-S distance in the anion 9 (2.722 ?) is ca. 0.5 ? longer than the sum of the covalent radii of these atoms but ca. 1 ? shorter than the sum of their van der Waals radii. According to the QTAIM and NBO analysis, the Se-S bond in 9 can be considered a donor-acceptor bond whose formation leads to transfer of ca. 40% of negative charge from PhS(-) onto the heterocycle. For various PhS(-)/1,2,5-chalcogenadiazole reaction systems, thermodynamics and kinetics were theoretically studied to rationalize the interchalcogen hypercoordination vs reduction to π-RA dichotomy. It is predicted that interaction between PhS(-) and 3,4-dicyano-1,2,5-telluradiazole (12), whose EA slightly exceeds that of 6 and 7, will lead to hypercoordinate anion (17) with the interchalcogen Te-S bond being stronger than the Se-S bond observed in anion 9.     

1,2,5-Thiadiazole 2-oxides: selective synthesis,structural characterization,and electrochemical properties

A new general procedure for the selective synthesis of 1,2,5-thiadiazole 2-oxides (including fused derivatives) 8a,b,c,g,h from the reaction of vic-glyoximes with S₂Cl₂ and pyridine in acetonitrile was elaborated together with general procedure for the synthesis of 1,2,5-thiadiazoles 7a–i, 10, 12, and 14 from the same starting materials and reagents. Molecular structures of 3,4-dimethyl-1,2,5-thiadiazole 2-oxide 8a and [1,2,5]thiadiazolo[3,4-b]quinoxaline 10 were confirmed by single-crystal X-ray diffraction. Electrochemical properties of 1,2,5-thiadiazole 2-oxides 8 were studied by cyclic voltammetry and different behavior was observed for monocyclic and benzo-fused derivatives. With compounds 8g and 17, previously unknown deoxygenation of 2,1,3-benzothiadiazole 1-oxides was discovered by electrochemical reduction, and resulted 2,1,3-benzothiadiazoles 7g and 19 were detected in the forms of their radical anions by EPR spectroscopy combined with DFT calculations.     

Chemiluminescence in the oxidation of phenyl-substituted silole radical anions and dianions

The emittor in the chemiluminescent electron transfer oxidation of the radical anions and dianions of 1,1-dimethyl-2,5-diphenyl- and 1,1-dimethyl-2,3,4,5-tetraphenylsilole is shown to be the parent compound. Chemiluminescence is reported in the oxidation of the radical anions of 1,2,5-triphenylphosphole, 2,3,4,5-tetraphenylthiophene-5-dioxide and 1,1-diphenyldibenzosilole.     

Isostructural metal-anion radical coordination polymers with tunable phosphorescent colors (deep blue, blue, yellow, and white) induced by terminal anions and metal cations

Five phosphorescent metal-anion radical coordination polymers based on a new anion radical ligand generated by in situ deprotonation of a stable zwitterionic radical are described. The N,O,N-tripodal anion radical ligand links metal cations, which leads to five isostructural coordination polymers, [M(3)(bipo(-.))(4)(L)(2)](n) (M=Cd or Mn, Hbipo(-.)=2,3'-biimidazo[1,2-a]pyridin-2'-one, L=Cl(-), HCOO(-) or SCN(-)). The isostructural coordination polymers exhibit novel one-dimensional spirocycle-like structures. Three isostructural Cd(II) coordination polymers display unusual phosphorescent color changes (blue, yellow, and white) induced by terminal anions. Significantly, the Cd(II) coordination polymer with terminal Cl(-) possesses moderate quantum yield, and shows a bright white-light phosphorescence emission, which is independent of excitation wavelength and can even be excited by visible light. Upon adjusting the metal cation to Mn(II), two isostructural Mn(II) coordination polymers reveal deep-blue-light phosphorescence emissions that are independent of terminal anions. As radical-based coordination polymers, some of them show antiferromagnetic interactions between radical species or radical and metal center.     

Application of a Double Aza-Michael Reaction in a 'Click, Click, Cy-Click' Strategy: From Bench to Flow

The development of a 'click, click, cy-click' process utilizing a double aza-Michael reaction to generate functionalized 1,2,5-thiadiazepane 1,1-dioxides is reported. Optimization in flow, followed by scale out of the inter-/intramolecular double aza-Michael addition has also been realized using a microwave-assisted, continuous flow organic synthesis platform (MACOS). In addition, a facile one-pot, sequential strategy employing in situ Huisgen cycloaddition post-double aza-Michael has been accomplished, and is applicable to library synthesis.     

Cyclosulfamides as Constraint Dipeptides: The Synthesis and Structure of Chiral Substituted 1,2,5-Thiadiazolidine 1,1-Dioxides: Evaluation of the Toxicity

A general synthesis for the preparation of chiral N-N′ substituted 1,2,5-thiadiazolidine 1,1-dioxides has been developed beginning with proteogenic amino acid, sulfuryl chloride, and dibromoethane. The selected chemistry and spectral properties of these compounds are examined. Overall, routes described are applicable to the synthesis of a variety of constrained dipeptidal sulfamides representing novel peptidomimetic scaffolds.     

Generation of naphthoquinone radical anions by electrospray ionization: solution, gas-phase, and computational chemistry studies

Radical anions are present in several chemical processes, and understanding the reactivity of these species may be described by their thermodynamic properties. Over the last years, the formation of radical ions in the gas phase has been an important issue concerning electrospray ionization mass spectrometry studies. In this work, we report on the generation of radical anions of quinonoid compounds (Q) by electrospray ionization mass spectrometry. The balance between radical anion formation and the deprotonated molecule is also analyzed by influence of the experimental parameters (gas-phase acidity, electron affinity, and reduction potential) and solvent system employed. The gas-phase parameters for formation of radical species and deprotonated species were achieved on the basis of computational thermochemistry. The solution effects on the formation of radical anion (Q(?-)) and dianion (Q(2-)) were evaluated on the basis of cyclic voltammetry analysis and the reduction potentials compared with calculated electron affinities. The occurrence of unexpected ions [Q+15](-) was described as being a reaction between the solvent system and the radical anion, Q(?-). The gas-phase chemistry of the electrosprayed radical anions was obtained by collisional-induced dissociation and compared to the relative energy calculations. These results are important for understanding the formation and reactivity of radical anions and to establish their correlation with the reducing properties by electrospray ionization analyses.     

Synthesis of N-substituted 1,2,5-thiadiazolidine and 1,2,6-thiadiazinane 1,1-dioxides from primary amines

Alkyl and aryl N-substituted 1,2,5-thiadiazolidine and 1,2,6-thiadiazinane 1,1-dioxides 6 were synthesized in good yields from the reaction of sulfuryl chloride with 2-chloroethylamine or 3-chloropropylamine hydrochlorides, respectively, followed by treatment with a primary amine and triethylamine, and ring closure with K₂CO₃ in DMSO.     

The chemistry of 1,2,5-thiadiazoles V. Synthesis of 3,4-diamino-1,2,5-thiadiazole and [1,2,5] thiadiazolo[3,4-b]pyrazines

The o-diamine, 3,4-diamino-1,2,5-thiadiazole ( 2 ), was synthesized from 3,4-dichloro-1,2,5-thiadiazole ( 3 ) hy three methods. Aqueous glyoxal cyclized 2 into [1,2,5]thiadiazolo[3,4–6]-pyrazine ( 14 ). 3,4-Dichloro-1,2,5-thiadiazole 1,1-dioxide ( 18 ) reaeted with 2 to give 1,3-dihydro-bis[1,2,5]thiadiazolo[3,4-b:3′,4′-e]pyrazine 2,2-dioxide ( 19 ). The reaction of 2 with selenium oxyehloride led to [1,2,5]selenadiazolo[3,4-c] [1,2,5]thiadiazole ( 12 ). Ring closure of 2,3-diaminoquinoxaline ( 4 ) with thionyl chloride or selenium oxychloride gave [1,2,5]thiadiazolo-[3,4-b]quinoxaline ( 21 ) and [1,2,5]selenadiazolo[3,4-b]quinoxaline ( 22 ), respectively. Sulfurous acid reduced 21 to the 4,9-dihydro derivative 23 , which was reoxidized to 21 with chloranil. Aqueous hase hydrolyzed 21 to 4 via the hydrated intermediate 24 . Aqueous glyoxal cyclized 4 to the covalent hydrate of pyrazino[2,3-b]quinoxaline ( 26 ), 27 , which was dehydrated to 26 . Compound 26 underwent rapid addition of two alcohols in a process analogous to covalent hydration.     

Intramolecular charge resonance in dimer radical anions of di-, tri-, tetra-, and pentaphenylalkanes

Intramolecular dimer radical anions of di-, tri-, tetra-, and pentaphenylalkanes were investigated on the basis of absorption spectral measurements during γ-radiolysis in 2-methyltetrahydrofuran (MTHF) glassy matrix at 77 K and theoretical calculations. The absorption spectrum of 1,1,2,2-tetraphenylethane (1,1,2,2-Ph(4)E) radical anion showed two bands in the near-infrared (NIR) region (900-2600 nm). One band observed at shorter wavelength than 2000 nm is assigned to the intramolecular charge resonance (CR) band between two phenyl groups of the 1,1-diphenylmethyl chromophore (1,1-dimer radical anion). The intramolecular CR band of the 1,1-dimer radical anion was observed for various alkanes having 1,1-diphenylmethyl chromophore such as 1,1,1-triphenylmethane (1,1,1-Ph(3)M), 1,1,1,1-tetraphenylmethane (1,1,1,1-Ph(4)M), and so on. The other intramolecular CR band observed at longer wavelength than 2200 nm is assigned to intramolecular dimer radical anion between two phenyl groups of the 1,2-diphenylethyl chromophore (1,2-dimer radical anion). The intramolecular CR band of the 1,2-dimer radical anion was observed for various alkanes having a 1,2-diphenylethyl chromophore, such as 1,1,2-triphenylethane (1,1,2-Ph(3)E), 1,1,2,2-Ph(4)E, and 1,1,1,2,2-pentaphenylethane (1,1,1,2,2-Ph(5)E) and so on. No dimer radical anion was observed for 1,n-diphenylalkanes (n > 2) without 1,1-diphenylmethyl chromophore. The relationship between the structure and negative charge delocalization over two phenyl groups connected by an sp(3) carbon is discussed.     

Molecular ions of 3,3′-bi(2-R-5,5-dimethyl-4-oxopyrrolinylidene) 1,1′-dioxides

The electrochemical reduction of 3,3′-bi(2-R-5,5-dimethyl-4-oxopyrrolinylidene) 1,1′-dioxides (R = CF₃, Me, Ph, Bu^t), which are cyclic dinitrons with conjugated C=C bond, in acetonitrile is an EE process producing stable radical anions and dianions, whereas the electrochemical oxidation is an EEC (R = Me, Ph) or EE process (R = Bu^t) with formation of radical cations (except for the case of R = CF₃) and dications (R = Bu^t) stable under standard conditions. Radical cations of the dioxides with R = Me, Ph, and Bu^t and radical anions of the whole series of the compounds studied, including R = CF₃, were characterized by ESR spectroscopy combined with electrochemical measurements and quantum-chemical calculations. The electrochemical behavior of the Bu^t-substituted dinitron is unique: the EE processes in the region of negative and positive potentials with formation of the dianion, radical anion, radical cation, and dication stable at T = 298 K were observed for the first time within one cycle of potential sweep in the CV curve measured in MeCN. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1148–1154, May, 2005.     

Ringerweiterung von 1,2-Thiazol-3(2H)-on-1,1-dioxiden und 3-Amino-2H-azirinen zu 4H-1,2,5-Thiadiazocin-6-on-1,1-dioxiden

Ring Enlargement of 1,2-Thiazol-3(2H)-one-1,1-dioxides and 3-Amino-2H-azirines to 4H-1,2,5-Thiadiazocin-6-one-1,1-dioxides Reaction of 3-amino-2H-azirines 2 with the 1,1-dioxides 4 and 7 of 1,2-thiazol-3(2H)-ones and 1,2-thiazoli-din-3-ones, respectively, in i-PrOH at room temperature leads to 4H-1,2,5-thiadiazocin-6(5H)-one-1,1-dioxides 5 (Scheme 2, Table) and the corresponding 7,8-dihydro derivatives 8 (Scheme 4), respectively. The structure of some of the new 8-membered heterocycles as well as the structure of the minor by-product 6 (Scheme 3) have been established by X-ray crystallography (Chapt. 4). The proposed reaction mechanism for the ring expansion to 5 and 8 (Scheme 2) is in accordance with previously published results of reactions of 2 and NH-acidic heterocycles and is further supported by the results of the reaction of 4a and the (1-¹⁵N)-labelled aminoazirine 2a *.     

Synthesis of 1,2,5-Thiadiazepine Derivatives by Ring Enlargement of 1,2-Thiazetidin-3-one 1,1-Dioxides with 3-Amino-2H-azirines

At 0° in MeCN, 2,2-disubstituted 3-amino-2H-azirines 1 and 4,4-disubstituted 1,2-thiazetidin-3-one 1,1-dioxides 7 react smoothly to give 1,2,5-thiadiazepin-6-one 1,1-dioxides of type 8 (Scheme 2). The reaction mechanism of this regiospecific ring enlargement to seven-membered heterocycles follows previously described pathways. The structures of 7a and 8b were established by X-ray crystallography (see Figs. 1 and 2).     

A Ring-Enlargement Reaction Yielding 1,2,5-Benzothiadiazonin-6-one 1,1-Dioxides

At room temperature or under reflux in MeCN, 3-amino-2H-azirines 2 and 3,4-dihydro-2H-1,2-benzothiazin-3-one 1,1-dioxide ( 4 ) give 1,2,5-benzothiadiazonin-6-one 1,1-dioxides 5 in fair-to-good yield (Scheme 2). The structure of this novel type of heterocyclic compounds has been established by X-ray crystallography of 5a (Fig.). A ring expansion via a zwitterionic intermediate of type A ' is proposed as the reaction mechanism of the formation of 5 .     

The ring opening of 3,4-dichloro-1,2,5-thiadiazole with metal amides. A new synthesis of 3,4-disubstituted-1,2,5-thiadiazoles

We have developed a new synthesis of 3,4-disubstituted-1,2,5-thiadiazoles. The methodology is based on the ring opening of readily available 3,4-dichloro-1,2,5-thiadiazole with metal amides to afford a stable synthon, which is then transformed into the 3,4-disubstituted-1,2,5-thiadiazole derivatives via two consecutive reactions with O-, S-, N- or C-nucleophiles.     

Multigram scale synthesis of 3,4- and 3,6-dihydro-2H-thiopyran 1,1-dioxides and features of their NMR spectral behavior

A new four-step synthesis of 3,4- and 3,6-dihydro-2H-thiopran-1,1-dioxides from dihydro-2H-thiopyran-3(4H)-one is reported. The title compounds are synthesized starting with oxidation of the ketone with a 30% aqueous solution of hydrogen peroxide in a mixture of AcOH-Ac₂O. The keto group is then reduced by sodium borohydride followed by mesylation and elimination of methanesulfonic acid under basic conditions (pyridine for 3,4-isomer and aqueous NaOH for 3,6-isomer). This sequence is simpler, than previously known methods, uses cheaper and more readily available reagents, and leads to 2H-thiopran-1,1-dioxides on multigram scale with 64% and 74% total yields, respectively. The structure and purity of the compounds were confirmed by 2D NMR and GCMS methods. The proposed method expands the means to access functionalized cyclic sulfones as building blocks in the synthesis of combinatorial libraries of new biologically active compounds.