Thione Function Research Articles

Synthesis, crystal structures and Hirshfeld analyses of phosphonothioamidates (EtO)2P(=O)C(=S)N(H)R (R = Cy, Bz) and their coordination on CuI and HgX2 (X = Br, I)

The phosphonothioamidates (EtO)2P(=O)C(=S)N(H)R (L1 R = Cy; L2 R = Bz) have been prepared by nucleophilic addition of K[(EtO)2P(=O)] to R–N = C=S and crystallographically analyzed. Both compounds are associated pairwise through strong intermolecular N–H···O bonding giving rise to 10-membered supramolecular macrocycles. This intermolecular bonding has also been studied by Hirshfeld analysis of L1 and L2. Complexation of L on CuI in MeCN solution affords the dinuclear rhomboid-shaped thione complexes [{Cu(μ2-I)2Cu}(η1-L)2] (1a,b). Crystallographic characterization of 1a reveals that L1 is ligated exclusively via the thione function to the trigonal Cu(I) centers, which are interconnected through a short Cu–Cu bond of 2.6207(4) Å. In the solid state, individual dimeric complexes are associated through intermolecular N–H···O bonding generating a supramolecular 1D ribbon. The dinuclear complexes [{XHg(μ2-X)2HgX}(η1-L)2] (2a X = Br, L = Cy; 2b X = Br, L = Bz; 2c X = I, L = Bz) were formed by stoichiometric addition of L to HgX2. The molecular structures of 2b and 2c have been elucidated by X-ray diffraction studies, which show that individual complexes are connected through intermolecular N–H···O bonding generating a supramolecular 1D ribbon. Treatment of L1 with two equivalents of HgBr2 produces the tetranuclear compound [Hg4Br8(κ1-L1)2] 3, whose unusual bromide-bridged architecture has been elucidated by X-ray crystallography.

Modification of the Hydrogen Bonds Network in a Hydroxyl Functionalized Dithiolene Ligand by HgX2 Complexation

AbstractLigand L (4,5‐bis[(2′‐hydroxyethyl)thio]1,3‐dithiole‐2‐thione) which crystallizes in the monoclinic system (P21/n) displays a 1‐D network generated by a succession of intra‐molecular and inter‐molecular hydrogen bonds. Weak π‐π and S···S interactions are also observed in the supramolecular structure. Reaction of L with one equivalent of mercury(II) iodide affords the adduct [HgI2L] (1a). The crystal structure of this complex shows that coordination occurs exclusively via the sulfur atom of the thione function (C=S). The ligation on HgI2 induces a change of the hydrogen bond pattern generated by the hydroxyl substituents: only intermolecular hydrogen bonds are present, organizing the adduct 1a in form of centrosymmetrical dimers in the solid state. The propensity of HgI2 to build‐up chains via μ2‐iodo ligand may be at the origin of the modification of the hydrogen bond network.

Room temperature ring opening of a 1,3-dithiole-2-thione at a dimolybdenum centre

The reaction of [Mo 2(CO) 4Cp 2] ( 1; Cp=η-C 5H 5) with 4,5-bis(carbomethoxy)-1,3-dithiole-2-thione at room temperature affords two products, both of which have been crystallographically characterised. In the first, [Mo 2{μ-SCS 2C 2(CO 2Me) 2}(CO) 5Cp 2] ( 2), the Mo≡Mo bond has been completely cleaved and the complex consists of the heterocycle η 2-side-bound through the thione function to a CpMo(CO) 2 unit, with an additional CpMo(CO) 3 group attached to the thione sulfur atom. In the second complex, [Mo 2{μ-SCSC(CO 2Me)C(CO 2Me)S}(CO) 3Cp 2] ( 3) the MoMo bond has been retained and partial ring opening of the heterocycle by CS bond cleavage has occurred, the latter being bonded as a thiolate ligand to one molybdenum and through the thione group to both metals.

Activation and Functionalization of Vinylic C−F Bonds by Transition Metal Compounds: The Factors Determining Reactions between Nucleophiles and a (Perfluorovinyl)diiron(I) Complex; Syntheses of Diiron Derivatives Containing New C−N, C−S, C−H and C−O Bonds

The reactions between alcohols ROH (R = Me, Et) and RR(OH)2 (RR = CH2−CH2) and the [perfluoro(sulfanyl)vinyl]diiron complex [{Fe(CO)3}2{µ-C(SMe)(CF3)CβCαF2}] (1) in THF at room temperature involve substitution at the Cα atom to give new (alkoxymethylene)thiaferracyclobutadiene compounds [{Fe(CO)3}2{µ-S(Me)C(CF3)CβCα(OR)2}] [R = Me (2a), Et (2b); RR = CH2CH2 (2c)]. Treatment of 1 with aniline and (methoxycarbonyl)hydrazine, bases of intermediate strength according to Pearson, produces α,β-substituted thiaferracyclopentadiene [{Fe(CO)3}2{µ-S(Me)C(CF3)Cβ(NHR)Cα(NHR)}] [R = Ph (5a), NHC(O)OMe (5b)] complexes. It is suggested that these compounds form through initial nucleophilic attack at Cα to give the zwitterionic intermediate [{Fe(CO)3}2{µ-S(Me)C(CF3)CC(NRH)2}] (f). Thermally induced C−F bond activation is a feature of these reactions. When 1 reacts with thioamides containing three “hard” competitive primary and secondary amine functions and one “soft” thione function, the nucleophile first attacks at Cα through a secondary amine and, in a second step, at Cβ through the thiol function to give α,β adducts [{Fe(CO)3}2{µ-S(Me)C(CF3)CβSC(=NR2)N(R1)Cα(Cβ−Cα)] [R1 = NH2, R2 = CH3 (6a); R1 = CH3, R2 = H (6b); R1 = R2 = CH3 (6c)] possessing novel iminothiazolidine systems fused to the five-membered metallacyclic ring. Treatment of 1 with acetylhydrazine, which has three “hard” nucleophilic functions, results in the formation of the compound [{Fe(CO)3}2{µ-S(Me)C(CF3)C(H)C(10)NNC(Me)O(C(10)−O)}] (7a), in which an oxadiazole function is fused to the thiaazaferracyclohexene ring. The position of the fluorine substituent on the CαCβCγ(CF3)S(Me) ring of ferracyclopentadiene complexes has been found to be the essential factor determining the specific activation of the C−F bond. A single fluoro substituent attached to the β-carbon atom of the chain can be activated by nucleophiles to give α,β adducts [{Fe(CO)3}2{µ-S(Me)C(CF3)Cβ(X)Cα(NRR′)}] [X = OR′′, R = R′ = R′′ = Me (3a); X = OR′′, R = R′′ = Me, R′′ = C(O)NMe2 (3b); X = SR′′ (4)]. In contrast, complexes in which a single fluorine atom is linked to the α-carbon atom do not undergo C−F bond cleavage reactions. X-ray structures of compounds 2a, 3b, 5a, 5b, 6a and 7a are reported.

Syntheses, crystal structures, and metal ion complexation studies of novel diaza‐18‐crown‐6 ligands containing aromatic thiol‐derived side arms

AbstractThe Mannich aminomethylation reaction of aromatic thiols has been used to produce diaza‐18‐crown‐6 ligands containing thiol‐derived side arms. Thiophenols were attached to the azacrown through N‐CH2‐S linkages even in the presence of hydroxy or acetamido groups. Heteroaromatic thiols containing N=C‐SH (or NH‐C=S) structural fragments were attached to diaza‐18‐crown‐6 by N‐CH2‐N linkages with the thiol becoming a thione function. X‐ray crystal structural analyses show the N‐CH2‐S and N‐CH2‐N linkages for some of the new macrocyclic compounds. Interactions of four of the new diaza‐18‐crown‐6 ligands with Na+, K+, Ba2+, Ag+, Zn2+, Cd2+, Ni2+, and Cu2+ were evaluated by calorimetric titration at 25° in methanol. The results show that these ligands form stable complexes with many of the metal ions studied.

Synthesis and solution studies of ruthenium(II) complexes with thiazole and antileukaemic drug thiopurines. Crystal structure of trans-dichlorotris(1,3-thiazole)(triphenylphosphine)ruthenium(II) ‡

The crystalline complexes [RuCl2(PPh3)2(thz)2] 1, [RuCl2(PPh3)(thz)3] 2, [Ru(H2tp)2(PPh3)(thz)]Cl2·2H2O 3·2H2O, [Ru(H2tg)2(PPh3)2]Cl2·2H2O·EtOH 4·2H2O·EtOH, [Ru(H2tprta)2(PPh3)2]Cl2·3H2O 5·3H2O, [Ru(H2tp)2(PPh3)2][CF3SO3]2·H2O·EtOH 6·H2O·EtOH, [Ru(H2tg)2(PPh3)2][CF3SO3]2·3H2O 7·3H2O, [Ru(H2tp)2(AsPh3)(MeOH)]Cl2·MeOH 8·MeOH, [Ru(bzim)2Cl2(PPh3)2] 9, and [RuCl2(PPh3)2(mpym)2] 10 (H2tg = purine-2-amino-6-thione, H2tp = purine-6-thione, H2tprta = purine-6-thione 2′,3′,5′-tri-O-acetylriboside, thz = 1,3-thiazole, bzim = benzimidazole, mpym = 4-methylpyrimidine) have been prepared from [RuCl2(PPh3)3] or [RuCl3(AsPh3)2(MeOH)] and the base in alcoholic solution under nitrogen. The structures of the complexes were investigated by X-ray diffraction (2), NMR, conventional spectroscopic techniques and electrochemical methods. All the complex molecules have a pseudo-octahedral co-ordination geometry. The donor set of 2 consists of a phosphorus atom, two chloride anions trans to each other and three thz ligands bound to the metal through nitrogen. The sulfur atom of thz does not show any donor ability. However, the thione function of purine is much more active and in complexes 3–8 the purine base is chelated through S and N(7) atoms. On refluxing a suspension of 2 and H2tp in ethanol compound 3 was obtained, which has a slight solubility in water. Electrochemical studies carried out on 7 in acetonitrile revealed a monoelectronic oxidation process at E½ 1.02 V. The [RuIII(H2tg)2(PPh3)2]3+ species which forms at this potential is relatively stable under the experimental conditions [25 °C; N2, 1 bar (105 Pa)] can be reversibly reduced to the starting compound which was recovered from the mixture. A molecular mechanics analysis, carried out for 1 and 2, produced a force field for this class of compounds and showed that the trans,trans,trans-[RuCl2(PPh3)2(thz)2] isomer of 1 is the most stable.

Synthesis and anti‐HIV‐1 activity of a series of 1‐(alkoxymethyl)‐5‐alkyl‐6‐(arylselenenyl)uracils and ‐2‐thiouracils

AbstractA series of 1‐(alkoxymethyl)‐5‐alkyl‐6‐(phenylselenenyl)uracils and ‐2‐thiouracils modified at the 3‐ and/or 5‐position of the C‐6 phenylselenenyl ring with methyl or fluoro substituent has been synthesized and tested for their ability to inhibit HIV‐1 replication. Lithiation of the acyclic uracil and 2‐thiouracil derivatives 11‐14 and 27‐32 with lithium diisopropylamide or lithium bis(trimethylsilyl)amide followed by reaction with an appropriate diaryl diselenide afforded 6‐arylselenenyl compounds 18‐26 after removal of the tert‐butyldimethylsilyl protecting group and 35‐47. Compounds 48‐54 were prepared from compounds 38‐44 by oxidative hydrolysis of the thione function. Of these compounds, 50 inhibited HIV‐1 replication in human T4 lymphoblastoid cells at a 50% effective concentration (EC50) of 0.0047 μM with a selectivity index of >42600.

Lipophilic disulfide prodrugs — syntheses and disulfide bond cleavage

Various drugs bearing a thiol or thione function were coupled with activated lipophilic thiol derivatives to afford unsymmetrical disulfides. Synthetic methods were developed to introduce one or two long alkyl chains into drug molecules in order to obtain highly lipophilic prodrugs. These might be suitable to form bilayers or for integration into liposomes. Disulfide bond cleavage was assessed by preincubation of the 6-MP prodrug 2 in serum followed by a bioassay. The preincubation period did not increase the inhibitory potency of the prodrug on lymphocyte proliferation as compared to the parent drug. Thus disulfide bond cleavage of prodrug 2 is assumed to be an active cellular process.

ChemInform Abstract: Radical Reactions Based on the Thione Function

Abstract The advantages of radical reactions for Organic Synthesis are summarised. Based on the idea of the disciplined radical, it is now possible to design radical reactions which afford a good yield of a single desired product. The system needs to contain a disciplinary group. In the case of radical reactions involving tin hydrides, it is the weak tin-hydrogen bond that is the disciplinary group. For the esters of thiohydroxamic acids, the disciplinary group is the thione function. Examples are given. Recent work has involved the design of stereospecific radical reactions. The hindrance around one chiral center is used to control the formation of the second. The ketal of (+)-(2R,3R) tartaric acid gives excellent stereospecificity (≃ 24:1) with retention of configuration. Furthermore, radicals, generated from isopropylidene uronic esters of N-hydroxy-2-thiopyridone, add readily to electron-poor alkenes in a stereospecific fashion, leading to functionalised chain-elongated furanosides and D-ribo-nucleosi...

Radical Reactions Based on the Thione Function

Abstract The advantages of radical reactions for Organic Synthesis are summarised. Based on the idea of the disciplined radical, it is now possible to design radical reactions which afford a good yield of a single desired product. The system needs to contain a disciplinary group. In the case of radical reactions involving tin hydrides, it is the weak tin-hydrogen bond that is the disciplinary group. For the esters of thiohydroxamic acids, the disciplinary group is the thione function. Examples are given. Recent work has involved the design of stereospecific radical reactions. The hindrance around one chiral center is used to control the formation of the second. The ketal of (+)-(2R,3R) tartaric acid gives excellent stereospecificity (≃ 24:1) with retention of configuration. Furthermore, radicals, generated from isopropylidene uronic esters of N-hydroxy-2-thiopyridone, add readily to electron-poor alkenes in a stereospecific fashion, leading to functionalised chain-elongated furanosides and D-ribo-nucleosi...

ChemInform Abstract: Some Novel Aspects of Regioselectivity in 1,3‐Dipolar Cycloadditions of 4H‐1‐Benzopyran‐4‐thione.

AbstractThe reaction of the title thione (I) with the nitrilimines (II) and (IV) leads to the cycloadducts (III) and (V), respectively.

Selectivity and Stereospecificity in Synthetic Applications of Radical Reactions

AbstractThe advantages of radical reactions for Organic Synthesis are summarised. Based on the idea of the disciplined radical, it is now possible to design radical reactions which afford a good yield of a single desired product. The system needs to contain a disciplinary group. In the case of radical reactions involving tin hydrides, it is the weak tin‐hydrogen bond that is the disciplinary group. For the esters of thiohydroxamic acids, the disciplinary group is the thione function. Examples are given. Recent work has involved the design of stereospecific radical reactions. The hindrance around one chiral center is used to control the formation of the second. The ketal of (+)‐ (2R, 3R) tartaric acid gives excellent stereospecificity (≌24:1) with retention of configuration.

Some novel aspects of regioselectivity in 1,3 dipolar cycloadditions of 4h-1-benzopyran-4-thione

4H-1-Benzopyran-4--thio)ie (1) reacted smoothly with nitrilimines (3a-e) to afford regioselectiue cycloadducts (4a-X) in good yields. In contrast, benzonitrile oxide (6) and aldonitrones (7a-d) reacted preferentially at the thione function. The unstable cycloadduct (B) or (9) ruptured to give as isolable products chromone (10) and phenyl isothiocyanate (11) and the tnioamides (12a-d). This indirectly proves the site of attack of the dipole at the thione group.

ChemInform Abstract: THE REACTION OF 1,6,6AΛ4‐TRITHIAPENTALENES WITH CARBENE AND NITRENE REAGENTS

AbstractDie Trithiapentalene (I) geben mit Azidoameisensäureethylester die 1:1‐Addukte (II) und mit Diphenyldiazomethan die 1:2‐Addukte (III).

The reaction of 1,6,6aλ4-trithiapentalenes with carbene and nitrene reagents

The reaction of some 1,6,6aλ4-trithiapentalenes with ethyl azidoformate provides 1:1 adducts, formulated as 4-thioacyl-methylene-1,3,2-dithiazine-2-carboxylic esters; and with diphenyldiazomethane, 1:2 adducts, formulated as 4-(3-propenylidene)-1,3-dithiins. In some cases 4-diphenylmethylenethiopyrans are isolated. The products arise by insertion at a disulfide type bond, or on a thione function of an initial reaction product.

ChemInform Abstract: OXIDATION PRODUCTS OF CYCLIC THIONES

AbstractIn zahlreichen Tabellen und unter Auswertung von 173 Lit.‐Stellen werden Oxidationsreaktionen an cyclischen Thionen untersucht.

OXIDATION PRODUCTS OF CYCLIC THIONES

Abstract A large number of cyclic thiones has been synthesized. These include alicyclic and heterocyclic thiones, the latter including those with potential aromatic character. It is the intention of this paper to summarize the reactions of a number of simple systems of this type with a variety of reagents which lead to modification of the thione function. Reactions may either lead to oxidation of the molecule, replacement of the thione sulfur atom by oxygen, or even replacement by hydrogen. Data are also included for some thiols which are capable of tautomerism with thiones and give similar or related products.

The oxidation of thiocarbonates with lead tetra-acetate and with peracids

Cyclic trithiocarbonates react rapidly with 1 mol. of lead tetra-acetate, which attacks the thione sulphur atom to form an oxythiocarbonyl compound. Cyclic mono- and di-thiocarbonates of the thione type also consume 1 mol. of the reagent, but in these compounds the thione function is converted into a carbonyl group; an exception is the catechol derivative, 1,2-thiocarbonyldioxybenzene, which gives a disulphide. Cyclic mono- and di-thiocarbonates not of the thione type are unchanged; relative to a trithiocarbonate they are also much less readily attacked by periodate.Reaction of a cyclic trithiocarbonate with 1 mol. of peracetic acid also gives the oxythiocarbonyl compound, but with an excess of the reagent the products are a disulphonic acid and a methylenedisulphonyl compound; formation of the latter involves the conversion of a thiocarbonyl function into a methylene group.Mechanisms are suggested for these transformations.