The Action of Carbon Disulfide and Sulfur on Enamines,Ketimines, and CH Acids

The reaction of sulfur, carbon disulfide, and enamines at room temperature leads mainly or exclusively to 3H-1,2-dithiole-3-thiones; these are occasionally accompanied by 2H-1,3-dithiole-2-thiones, which can also be prepared by a modified procedure. Many enamines react with sulfur at room temperature to form thioamides. At about 50°C, enamines of acetophenone give 2-benzylidene-4-phenyl-2H-1,3-dithiol. The action of isothiocyanates and sulfur on enamines leads to the formation of thiazolidine-2-thiones. 2H-Thiopyran-2-thiones can be prepaAred from enamines or dienamines with carbon disulfide at room temperature. The reaction of ketimines (Schiff bases) with carbon disulfide and sulfur yields 3H-1,2-dithiole-3-thiones or isothiazoline-5-thiones. The reaction of alkynes with sulfur and carbon disulfide leads to 2H-1,3-dithiole-2-thiones. Nitriles containing active methylene groups react with carbon disulfide and sulfur to form 5-amino-3H-1,2-dithiole-3-thiones. When isothiocyanates are used instead of CS₂, the reaction leads to δ⁴-4-amino-thiazoline-2-thiones.     

Reaction of 3-oxo-3-R<Superscript>1</Superscript>-<Emphasis Type="Italic">N</Emphasis>-R<Superscript>2</Superscript>-propanethioamides with 2-amino-5-R-pyridines

Direction of a reaction between 3-oxo-3-R¹-N-R²-propanethioamides and 2-amino-5-R-pyridines in acetic acid depends on the structure of initial thioamides: at R¹ = Me, R² = Ar, Et 2-methyl-7-R-4H-pyrido[1,2-a]-pyrimidine-4-thiones are obtained, and at R¹ = Ar, R² = Me form 1-methyl-5-(N-methylaminothiocarbonyl)-4,6-diaryl-1,2-dihydropyridine-2-thiones.     

Synthesis of substituted N-(2,4-dioxo-1,2,3,4-tetrahydroquinazolinyl)benzamides and N-(2-thiono-4-oxo-1,2,3,4-tetrahydroquinazolinyl)benzamides

Substituted N-(2,4-Dioxo-1,2,3,4-tetrahydroquinazolinyl)benzamides ( 3a-g ) and substituted N-(2-Thiono-4-oxo-1,2,3,4-tetrahydroquinazolinyl)benzamides ( 4a-g ) were synthesized in one step from the reaction of methyl anthranilate with 2-aryl-1,3,4-oxadiazolin-5-ones ( 1a-g ) and 2-aryl-1,3,4-oxadiazoline-5-thiones ( 2a-g ), respectively, in m-cresol at 150–160°. Alternative routes leading to the formation of 3a and 4a are also reported.     

Zur Reaktion von Diphenoxyphosphorylchlorid mit N,N-disubstituierten Harnstoffen – Bildung von phosphorylierten Biuret-Verbindungen

Reaction of Diphenoxyphosphorylchloride with N,N-disubstituted Ureas – Formation of Phosphorylated Biuret Compounds N′,N′-disubstituted N-diphenoxyphosphorylureas, (PhO)₂P(O)? NH? CO? NR¹R² (R¹ = R² = Et, 1 ; n-Pr, 2 ; n-Bu, 3 ; i-Bu, 4 ; R¹ = Me and R² = Ph, 5 ) as well as phosphorylated biuret compounds, (PhO)₂P(O)? NH? CO? NH? CO? NR¹R² are obtained in the reaction of diphenoxyphosphorylchloride with N,N-disubstituted ureas and triethylamine. The biuret derivatives are formed via (PhO)₂P(O)NCO. Their yield rises if the reaction is carried out without amine. The X-ray crystal structure analysis of (PhO)₂P(O)? NH? CO? NH? CO? NPr₂, 8 , shows that dimers exist in the crystal with intermolecular as well as intramolecular hydrogen bonds. The framework formed by atoms P? N1? C1(O4)? N2? C2(O5)? N3(C3)C6 is planar. The existence of a rotation barrier along the bond C2–N3 was detected by NMR spectroscopy.     

Double stereoselective coordination of chiral N,S ligands: Synthesis,coordination chemistry and utilization in Pd‐catalyzed allylic alkylation

A series of chiral pentane‐2,4‐diyl‐based thioether‐amine ligands [ 4 and 5 ; (R,S)‐ and (S,S)‐R¹SCH(CH₃)CH₂CH(CH₃)NHR², respectively, where 4a R¹ = iPr, R² = Ph; 4b R¹ = tBu, R² = Ph; 4c R¹ = 1‐Ad, R² = Ph; 5a R¹ = iPr, R² = Ph; 5b R¹ = tBu, R² = Ph; 5c R¹ = 1‐Ad, R² = Ph; 5d R¹ = iPr, R² = 4‐MeOC₆H₄; 5e R¹ = iPr, R² = 4‐MeC₆H₄; 5f R¹ = iPr, R² = 3,5‐Me₂C₆H₃] with stereogenic S‐ and N‐donor atoms has been prepared starting from cyclic sulfates via optically pure γ‐aminoalcohol or 2,4‐dimethylazetidine intermediates. The synthesis of the novel diastereomerically related ligand sets 4 and 5 was accomplished starting from the same source of chirality. The modular ligand structure and the novel synthetic strategies developed for their synthesis allowed the easy modification of the ligands’ (i) S‐ and (ii) N‐substituents, as well as (iii) the relative stereochemistry within the ligand backbone. Six‐membered [Pd(N,S)Cl₂]‐type chelate complexes of the diastereomerically related ligands 4a and 5a were synthesized and characterized by X‐ray crystallography in the solid phase, by density functional theory calculations and in solution by NMR spectroscopy. The coordination of 5a resulted in the formation of a single chair conformation by the stereospecific locking of both stereolabile (N and S) donor atoms. In contrast, compound 4a forms rapidly equilibrating palladium species due to the fast inversion of the sulfur donor. Ligands with stereochemically fixed donor atoms provided robust and efficient catalytic systems that can be effectively applied in alkylene carbonates as green reaction media. Remarkably, the phosphine‐free catalysts are air‐stable, and at room temperature in the presence of moisture gave excellent ee’s (up to 93%) in asymmetric allylation processes thanks to the double stereoselective coordination.     

New aspects of reactions of methyl (thio)ureas with benzil

New pathways of reaction between 1-methylthiourea or 1-methylurea and benzil bring about new derivatives of (2S*,3aR*,6aS*)-perhydro-3aH-[1,3]dioxolo[4,5-d]imidazole and racemic (4S*,5R*)-4-alkoxy-5-hydroxy-1-methyl-4,5-diphenylimidazolidine-2-thiones. Some of the obtained urea-and thiourea derivatives were characterized by X-ray diffraction, which showed their supramolecular organization governed by the directionality of hydrogen bonds at the acceptor side C=O or C=S groups.     

Synthesis,characterization, crystal structure,and antibacterial evaluation of Ni (II) complex with new dithiophosphorus compound

The reaction of 2,4-bis (4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawesson^’s reagent) with phenylethylamine produced [H₃NCH₂CH₂C₆H₅]⁺ [(C₆H₅CH₂CH₂NH)(p C₆H₄OMe)PS₂]^? (1). Furthermore, reaction of 1 with NiCl₂ in dry methanol led to the novel complex 2. The compounds were characterized by ¹H and ³¹P NMR, IR spectroscopy, and elemental analysis. A single crystal X-ray structure of complex 2 showed that the nickel complex is square planar. The complex formed a supramolecular structure via intermolecular S1…H7B and O1…H2N2 hydrogen bonds. The X-ray crystallography of complex showed [R²₂](18) and R⁴₄(18) motifs in the monomers were connected to each other via S1…H7B, O1…H2N2 hydrogen bonds with donor–acceptor distance of 2.89 and 2.51 Å, respectively. The new compounds were additionally tested in view of their antibacterial properties.     

Bromination of 6-dibromomethyl-6-methylcyclohexyl-2,4-dien-1-one

Bromination of 6-dibromomethyl-6-methylcyclohexyl-2,4-dien-1-one (I) with molecular bromine was studied at different ratios of reactants and varied reaction time. A number of tri-, tetra-, penta-, and hexabromo derivatives was obtained, which were characterized by ¹H, ¹³C, IR, UV spectroscopy and elemental analysis. The molecular structure of (2R,3R,4S,5S,6R)-2-dibromomethyl-2-methyl-3,4,5,6-tetrabromocyclohexan-1-one (V) was revealed using XRD. It was shown that 2-bromo-6-dibromomethyl-6-methylcyclohexyl-2,4-dien-1-one (III) upon standing for six months at room temperature dimerized quantitatively via Diels-Alder reaction to form IX. Dimer IX was investigated by the methods of cyclic voltammetry (CVA) and rotating disk electrode (RDE) in a solution of DMF on glassy carbon electrode.     

Easy access to medium rings by entropy/strain reduction,Part 3. Competition between dihydroazepine and enamine formation in reaction of tetrahalosubstituted dibromides with primary amines

The reaction of Z,Z‐2,3,4,5‐tetrahalo‐2,4‐dien‐1,6‐dibromides ( 3 , R¹ ‐ R⁴ = Cl, Br) with primary amines in the presence of potassium carbonate leads to both the dihydroazepines 4 and secondary enamines 5 . The formation of enamine is suppressed with toluene sulfonamide as nitrogen source. (2Z,4Z)‐2,3,4,5‐Tetrabromo‐hexa‐2,4‐diene‐1,6‐diol (2, R¹ ‐ R⁴ = Br) is atropisomeric in solution.     

Binukleare Nickel(0)-Alkin-Koordinationsverbindungen – Zusammenhang zwischen Ligandperipherie und supramolekularer Struktur

Binuclear Nickel(0) Alkyne Coordination Compounds – Correlation between Ligand Periphery and Supramolecular Structure Reaction of Ni(cdt: 1,5,9-cyclododecatriene) with functionalized alkynes and subsequent reaction with ethylenediamines gives binuclear compounds of the type (diamine)Ni(μ-alkyne)Ni(alkyne). Compounds with alkyne-diols (N?N)Ni₂(HOR¹R²C? C?C? CR¹R²OH)₂ show supramolecular structures in which two identical intramolecular and one intermolecular hydrogen bonds are realized. 1 and 2 (chelate ligand in each case N,N,N′,N′-tetramethylethylenediamine, TMEDA, in 1 R¹ = R² = Me, in 2 R¹ = R² = Et) polymer-like chains are built up by connecting the binuclear units. Via two intermolecular hydrogen bonds per organometallic unit in 1 and via one intermoleculare hydrogen bond in 2 the chains are connected to give double chains. By substitution of one methyl group of TMEDA by hydrogen ( 3 : R¹ = R² = Me) a polymerlike network is produced by connecting the polymer-like chains. In compound 4 in which one of the methyl groups of TMEDA is substituted by CH₂CH₂NMe₂ the polymer-like chains remain unconnected. In 5 (diamine = TMEDA, alkyne = (CH₃)₃C? C?C? CMe₂OH) one intermolecular hydrogen bond per organometallic unit is observed forming again polymer-like chains that are independent of each other.     

2,4-Bis(4-methylpheylthio)-1,3,2λ5,4λ5-dithiadiphosphetan-2,4-dithion: Ein neues Reagens zur Schwefelung von N,N-disubstituierten Amiden

2,4-Bis(4-methylphenylthio)-1,3,2λ⁵,4λ⁵-dithiadiphosphetane-2,4-dithione: A New Reagent for Thiation of N,N-Disubstituted Amides As a new reagent for the thiation of amides, the easily accessible 2,4-bis(4-methylphenylthio)-1,3,2λ⁵,4λ⁵-dithiadiphosphetane-2,4-dithione ( 9 ) shows a remarkable selectivity. This selectivity – the preferred thiation of N,N-disubstituted amides – is complementary to the one of the well known Lawesson reagent. Thiation of diamides of type 2 with 9 leads via cyclization of the corresponding dithiodiamides to 1,3-thiazole-5(4H)-thiones 1 (Scheme 3).     

Bis(arylimido) Molybdenum(VI) Amidinate and Guanidinate Complexes; Molecular Structures of [(ArN)2MoMe{N(Cy)C[N(i‐Pr)2]N(Cy)}] (Ar = 2,6‐i‐Pr2C6H3; Cy = Cyclohexyl) and [(2,6‐i‐Pr2C6H3N)2MoCl2] · [NH=C(C6H5)CH(SiMe3)2]

The reaction of [(ArN)₂MoCl₂] · DME (Ar = 2,6‐i‐Pr₂C₆H₃) ( 1 ) with lithium amidinates or guanidinates resulted in molybdenum(VI) complexes [(ArN)₂MoCl{N(R¹)C(R²)N(R¹)}] (R¹ = Cy (cyclohexyl), R² = Me ( 2 ); R¹ = Cy, R² = N(i‐Pr)₂ ( 3 ); R¹ = Cy, R² = N(SiMe₃)₂ ( 4 ); R¹ = SiMe₃, R² = C₆H₅ ( 5 )) with five coordinated molybdenum atoms. Methylation of these compounds was exemplified by the reactions of 2 and 3 with MeLi affording the corresponding methylates [(ArN)₂MoMe{N(R¹)C(R²)N(R¹)}] (R¹ = Cy, R² = Me ( 6 ); R¹ = Cy, R² = N(i‐Pr)₂ ( 7 )). The analogous reaction of 1 with bulky [N(SiMe₃)C(C₆H₅)C(SiMe₃)₂]Li · THF did not give the corresponding metathesis product, but a Schiff base adduct [(ArN)₂MoCl₂] · [NH=C(C₆H₅)CH(SiMe₃)₂] ( 8 ) in low yield. The molecular structures of 7 and 8 are established by the X‐ray single crystal structural analysis.     

Synthesis of 1,2,4,5-Tetrakis(1,2,4-Triazolyl) Benzene and 1,2,4,5-Tetrakis(1,3,4-Oxadiazolyl) Benzene Derivatives

Abstract

A series of 1,2,4,5-tetrakis(1,2,4-triazolyl)benzenes and 1,2,4,5-tetrakis(1,3,4-oxadiazolyl)benzenes was synthesized by nucleophilic addition of sodium salts of 4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thiones and 1,3,4-oxadiazole-2(3H)-thiones to 1,2,4,5-tetrakis(bromomethyl)benzene. The structure of the newly synthesized compounds was confirmed by elemental analysis, IR and ¹H and ¹³C NMR spectra.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: 1H and 13C NMR spectra of products (Figures S1-S24).     

Conformational and stereoelectronic control in ring-transformations of cis-4,5-dialkoxytetrahydropurine-2,6,8-triones

Divergent acid-catalysed ring-openings of 4,5-dimethoxytetrahydropurine-2,6,8-triones 2 at position 4, yielding 1-(5-methoxyhydantoin-5-carbonyl)ureas 4 (R⁷ = Me) or 5-methoxy-5-ureido-2,4,6-pyrimidinetriones 5 (R⁷ = H), can be rationalized by assuming a preference for one of two conformational isomers of the cis-fused system, associated with the N-substitution effects. Intramolecular transamidation 5 → 4 presumably occurs via a bicyclic acid aminal type intermediate 3 , heretofore misassigned as the reaction product. A curious base-catalysed rearrangement was encountered with the 5 (R¹ = R³ = Me, R⁷ = H) cases, which afforded 5-methoxy-1,5-bis(methylaminocarbonyl)hydantoins 7 . Remarkable stability of the conformationally rigid propellane type 4,5-ethylenedioxytetrahydropurine-2,6,8-triones 9 toward acids, shows that the mode of ring-opening at position 4 is controlled by powerful Stereoelectronic factors. However, an alternative ring-opening at the 1,6-bond has occurred on heating aqueous solutions of 9a (R⁷ = H); the ensuing decarboxylative rearrangement leads to 1,3-dimethylallantoin ( 12 ) and its precursor, 1-(2-hydroxyethoxy)-2,4-dimethyl-3,7-dioxo-2,4,6,8-tetraazabicyclo[3.3.0]octane( 11 ).     

Synthesis of 4-(pyrazol-5-yl)-1,2,4-triazole-3-thiones

Condensation of pyrazolyl isothiocyanates 2 with N-substituted hydrazines provided the 2-methyl/phenyl-4-(pyrazol-5-yl)thiosemicarbazides 3 . Cyclization of 3 with formic acid-acetic anhydride or with triethyl orthoacetate-acetic anhydride provided 4-(pyrazol-5-yl)-l,2,4-triazole-3-thiones 4a-f and 5-methyl-4-(pyrazol-5-yl)-1,2,4-triazole-3-thiones 4g-I respectively.     

Synthesis and structure of new 2,4-dicyano-6-oxo-3-phenylbicyclo[3.2.1]octane-2,4-dicarboxylates

The sequential reaction of furfural with cyclic secondary amines and further with benzaldehyde and cyanoacetates affords new 2,4-dicyano-8-(R₂N)-6-oxo-3-phenylbicyclo[3.2.1]-octane-2,4-dicarboxylates as rac-(1R,2R,3R,4S,5S,8R)-diastereomers. The structures of the reaction products were determined by X-ray diffraction.

     

Synthesis and crystal structures of novel lithium- and palladium-1-azaallyls

Treatment of (RH₂C)₂C₅H₃N-2,6 (R=SiMe₃) with BuⁿLi followed by addition of Me₃SiCl gave the tetrasilyl pyridine derivative (R₂HC)₂C₅H₃N-2,6 1 in high yield. Further lithiation of 1 with BuⁿLi and reaction of the intermediate with PhCN led to the new lithium-1-azaallyl [Li{N(R)C(Ph)C(R)(C₅H₃N-2,6)(CHR₂)}]₂2, while metallation of the previously described di-lithium compounds [Li{N(R)C(R^′)CH}₂(C₅H₃-2,6)]Li(tmen)_n (R=SiMe₃, R^′=Bu^t, n=1 or R=SiMe₃, R^′=Ph, n=2) with PdCl₂(PhCN)₂ yielded the novel metallacycles [Pd{{N(H)(R)C(R^′)CH}{N(SiMe₂CH₂)C(R^′)CH}C₅H₃N-2,6}] 3 (R^′=Bu^t) and [Pd{{N(R)C(R^′)CH}{N(R)(H)C(R^′)CH}C₅H₃N-2,6}₂] (R^′=Ph) 4 in moderate to low yield. Compound 3 is unusual in being the first example of a crystallographically characterised PdNSiC heterocycle which is believed to be formed via an intramolecular CH-activation of a trimethylsilyl group by Pd(II). All four compounds were fully characterised by NMR-spectroscopy, microanalysis (not 4) and X-ray diffraction.     

Arylation of halogenated thiophene carboxylate via Suzuki–Miyaura reaction: Anti-bacterial study against clinically isolated extensively drug resistant Escherichia coli sequence type 405 and computational investigation

In present study, Pd(0) catalysed Suzuki-Miyaura cross coupling reaction was used to synthesize 2,4-biarylphenyl-5-arylthiophene-2-carboxylate (7a–7f) and 2-aryl-4-chlorophenyl-5-arylthiophene-2-carboxylate derivatives (8a–8l) in moderate to good yields. While 2,4-dibromophenyl-5-bromothiophene-2-carboxylate (4) and 2-bromo-4-chlorophenyl-5-bromothiophene-2-carboxylate (5) were synthesized via Steglich esterification of 5-bromothiophene-2-carboxylic acid (1) with 2,4-dibromo phenol (2) and 2-bromo-4-chlorophenol (3) in the presence of N, N?-dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP). ¹H and ¹³C NMR were used to confirm all of the compounds. To screen out the most active lead compounds, binding interactions of all synthesized compounds with MurD and MurE Escherichia coli proteins were evaluated theoretically via molecular docking studies indicating the good binding affinities. DFT calculations were performed out by using DFT-B3LYP/3-21g and structural and reactivity parameters were calculated. Compounds 5, 8b, 8e, 8h, and 8j have demonstrated potential reactivities and charge distributions that indicate their efficiency towards biological targets. These chemicals were tested in vitro for antibacterial activity against Gram-negative bacteria (Escherichia coli) at different concentrations based on theoretical results. The total results were quite close to the theoretical predictions and compound 8j was found to be having the greatest potential value, strongest binding affinities, and a promising antibacterial agent with MIC value of 50 mg/ml against Escherichia coli.     

Exo- and endo-palladacycles derived from (4R)-phenyl-2-oxazolines

Two novel oxazoline-derived palladacycles bearing an endo- or exo-CN bond were prepared by direct ortho-palladation of (R)-2,4-diphenyl- or (R)-2-methyl-4-phenyl-2-oxazolines, respectively. The structures of the palladacycles' dimeric forms and corresponding mononuclear PPh₃-derivatives were confirmed by IR, ¹H, ¹³C and 2D NMR spectroscopy. An X-ray diffraction study of the μ-chloro-dimeric cyclopalladated derivative of (R)-2,4-diphenyl-2-oxazoline proved the endo structure of the palladacycle.     

Studies on organophosphorus compounds—XXVIII: Syntheses of 3H-1,2-dithiole-3-thiones and 4H-1,3,2,-oxazaphosphorine derivatives from the dimer of p-methoxyphenyl-thionophosphine sulfide and der

Unsubstituted and 2-monosubstituted 3-oxo esters react with the dimer of p-methoxyphenyl-thionophosphine sulfide (1) and elemental sulfur in anhydrous toluene at 110° to give the corresponding 3H-1,2-dithiole-3-thiones (2) in nearly quantitative yields (90–95%). Ethyl 2,2-dimethyl 3-oxo-butanoate, failing to react in toluene at 110°, decomposes into a complex mixture at 140° in anhydrous xylene. Also secondary and tertiary 3-oxo-amides such as acetoacetanilide and N,N-dimethylacetoacetamide produce the corresponding 3H-1,2-dithiole-3-thiones (2) upon treatment with 1 and elemental sulfur. Primary 3-oxo-amides and 3-oxo-nitriles react with 1 in anhydrous toluene at 110° giving in all cases investigated, derivatives of 2,3-dihydro-2(4-methoxyphenyl)-4H-1,3,2-oxazaphosphorine-4-t as main products (70–95%). ¹H, ¹³C and ³¹P NMR data are tabulated and reaction mechanisms are suggested.