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Cyclopenta[b]thiopyran, isomeric to benzo[b]thiophene while isoelectronic to azulene, is involved as a building block to construct soluble organic semiconductors for field-effect transistors. Two series of angular-shaped heteroarenes based on cyclopenta[b]thiopyran, that is, Cn-SS (n = 4, 6, 8, 10) with different linear alkyl groups and C8-SS-Clm (m = 2, 3, 4) with chlorides substituted at different positions, have been straightforward synthesized. The obtained seven S-heteroarenes exhibit intriguing and similar photophysical and electrochemical properties, such as near-infrared absorption and high-energy levels of the highest occupied molecular orbitals. Nevertheless, the S-heteroarenes with identical π-conjugated skeletons demonstrate completely different molecular packing structures, which is proofed to be the key determinate factor for the charge carrier mobilities. Upon the engineering of the pendant alkyl lengths, the highest hole mobility in the Cn-SS series is achieved for C8-SS (1.1 cm2 V-1 s-1) with moderate alkyl length. The further incorporation of chlorides on C8-SS results in the shortened intermolecular H···S contacts and the interplane distances. Most interestingly, when chlorine-containing chloroform and chlorobenzene are used as crystallization solvents, single crystals of C8-SS-Clm with different packing structures are produced owing to the intermolecular interactions among the solute and solvent molecules. Upon further engineering of the chlorination position and the crystallization solvent, the maximum hole mobility in the ambient air improves to 2.7 cm2 V-1 s-1 for C8-SS-Cl2 crystallized from chlorobenzene, suggesting that the introduction of the accessible chlorides is a feasible pathway to engineering the crystal structures and controlling the charge transport characteristics.

In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one(1)and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione(2)was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol(3, 4), 3,4-dihydroquinoline(7, 8)and thiopyran(10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9)was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities againstCandida albicansandAspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid(9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent.

Structurally unique thiopyranodipyridine alkaloids xylaridines C (1) and D (2) were isolated from the fungus Xylaria longipes. Their structures were established by comprehensive spectroscopic analysis combined with single-crystal X-ray diffraction and electron-capture detection (ECD) calculations. Compound 1 possesses two piperidine moieties fused with a centered thiopyran ring, while compound 2 is a dimer of 1. Compound 1 was resoluted into optical pure enatiomers (+)-1 and (-)-1 by chiral HPLC. Moreover, compound 2 was resoluted into an optically pure compound (+)-2 and a mixture of (-)-2 and meso-2. Plausible biosynthetic pathways of compounds 1 and 2 are proposed.

3-Chloro-3-chlorosulfenyl-4���-methylspiro[chroman-2,1���-cyclohexane]-4-one (4) was prepared from the reaction of spiro 4���-methylcyclohexan-1���,2-chroman-4-one (3) with thionyl chloride according to reported method. Furthermore, treatment of compound 4 with potassium iodide gave 1,2-bis (3-chloro-4���-methylspirochroman-2,1���-cyclohexyl-4-one)disulfane (6) in addition to 4,4���-dimethyltrispiro[cyclohexane-1,2���-chroman-3���,2���-2H-chromeno[3,4-e][1,3,4]-oxadithiin-5���,1���-cyclohexan]-4���-one (5). The formation of compound 5 could be presumably explained via the formation of unstable intermediate oxo-thioketone A. The formation of the latter intermediate A was confirmed chemically through the thermal reaction of compound 5, or compound 6 with 1,3-homodiene such as: 1,3-cyclohexadiene, isoprene, and 2,3-dimethyl-1,3-butadiene to afford the products 7���9, respectively. The chemical structures of the newly prepared compounds were confirmed by spectroscopic methods (IR, 1H & 13C NMR, and MS). The synthesized compounds were evaluated against lung (A549), prostate (PC3), pancreatic (PACA2), and breast (MDA) cancer cell lines. Compound 3 exhibited prominent cytotoxicity against A549, PC3, and PACA2 cancer cell lines with IC50 values from 12.4 to 16.1 ��M, which was comparable or superior to the reference drug (Doxorubicin). Compounds 7���9 showed better cytotoxicity against breast (MDA) cancer cell line than the reference drug (Doxorubicin).

S-heteroarenes containing cyclopenta[b]thiopyran moieties were synthesized via intramolecular ring-expanding cycloisomerization from 1-acetyl-2-thienyl-substituted precursors catalyzed by PtCl2. In...

The first sulfhydryl-directed iridium-catalyzed C-H/diazo coupling and tandem annulation of naphthalene-1-thiols has been developed. The framework of naphtho[1,8-bc]thiopyrans was constructed in a one-step reaction with good yields. This transformation provides a practical synthetic route for the widely used naphtho[1,8-bc]thiopyran derivatives.

A convenient method for the preparation of 1,1-dihydropolyfluoroalkanesulfinyl chlorides has been developed basing on the oxidative chlorination of 1,1- dihydropolyfluoroalkyl thioacetates. The dehydrochlorination of the sulfinyl chlorides leads to the formation of new polyfluoroalkylsulfines (fluorinated thioaldehyde-S-oxides). The thermal decomposition of the sulfines results in formation of the symmetrical polyfluorinated alkenes, whereas the reactions of the sulfines with 1,3-dienes afford 2 -(polyfluoroalkyl)-3,6-dihydro-2H-thiopyran-1-oxides.

Methyl 4-oxotetrahydro-2H-thiopyran-3-carboxylate as a CH-acid undergoes a mild reaction with acetylenic esters in the presence of triphenylphosphine to produce phosphorus ylides possessing thiopyran-4-one ring moiety. The resulted phosphorus ylides when heated in toluene afforded functionalized thiopyran derivatives through intramolecular Wittig reaction.

A synthetic route to functionalized α-(polyfluoroalkyl)thiophenes based on the reactions of ring contraction of polyfluoroalkyl substituted thiopyran derivatives has been explored. Potent 6-membered precursors for the preparation of thiophenes were obtained by the addition of bromine to the double bonds of 2-chloro-2-(trifluoromethyl)-3,6-dihydro-2 H -tetrahydrothiopyran and 6-(polyfluoroalkyl)-2 H -thiopyrans. The reactions of the resulted 4,5-dibromo-2-chloro-2-(trifluoromethyl)tetrahydrothiopyrans and trans -3,4-dibromo-6-(polyfluoroalkyl)-3,4-dihydro-2 H -thiopyrans with sodium acetate in acetic acid produced 2-(acetoxymethyl)-5-(polyfluoroalkyl)thiophenes. Base-catalyzed methanolysis of the acetoxymethyl derivatives allowed preparing the corresponding 2-(hydroxymethyl)-5-(polyfluoroalkyl)thiophenes. The mechanism, which includes formation and nucleophilic cleavage of thiiranium cations, has been suggested for the transformation of dibromothiopyran derivatives to substituted thiophenes.

A series of 3″,5″-diaryl-3″H-dispiropyran/thiopyran[4,2′-chroman-3′,2″-[1,3,4-thiadiazol]-4′-ones 5a-n were synthesized from the reaction of trispiro[tetrahydropyran(tetrahydrothiopyran)-4,5′-2H-ch...

A highly efficient and atom-economic dual reaction manifold has been developed to synthesize 4H-thiopyran and 4,5-dihydrothiophene frameworks via regioselective intramolecular C-S fusion of α-allyl-β'-oxodithioesters. The ring size of the sulfur-heterocycles has been efficiently tuned by the use of two different catalytic systems. Palladium activates the Cδ-H of the allyl termini and facilitates the intramolecular Cδ-S coupling to furnish six-membered thiopyran skeletons exclusively. Conversely, the allylic double bond of the same substrate has been activated by BF3·Et2O to promote the Cγ-S cyclization leading to the formation of a five-membered dihydrothiophene nucleus.

A one-pot synthesis of functionalized thiopyran derivatives via a Cu-catalyzed multicomponent reaction of sulfonyl azides, arylacetylenes and dipotassium 2,2-dicyanoethylene-1,1-dithiolate, generated from malononitrile and CS2, has been developed. When alkylacetylenes were used as the terminal alkynes, N-(alkanethioyl)-N-(2,2-dicyanoethanethioyl)methanesulfonamides were obtained in good yields.

Two spiroheterocyclic 2H-azirin-3-amines, 1f and 1g, were shown to be useful synthons for the dipeptides N-(4-aminotetrahydro-2H-pyran-4-yl)prolinate (Thp-Pro) and the corresponding thiopyran derivative, Tht-Pro, respectively. By coupling of 4-bromobenzoic acid with 1f or 1g and saponification, followed by repeating the coupling and saponification steps, oligopeptides of type 4-BrBz-(Thp-Pro)n-OMe and 4-BrBz-(Tht-Pro)n-OMe were prepared, and their conformations were evaluated in solution by NMR techniques and in the crystalline state by X-ray crystallography. All of these sterically highly congested oligopeptides adopt fairly rigid helical conformations. It is interesting to note that the hexapeptide with Thp forms a 310-helix, whereas the Tht analog has a beta-bend ribbon spiral conformation.

A new series of mono- N -sulfonamides of C 2 -symmetrical 2′-bipyrrolidine have been designed, synthesized, and successfully applied as the organocatalysts to the enantio- and diastereoselective Michael addition of 4 H -thiopyran-4-one to a variety of nitroolefins. Catalyst 10 was identified in the examinations to exhibit more superior catalytic ability than the traditional chiral pyrrolidine catalysts, giving high chemical yields, excellent diastereo- and enantioselectivities (up to 99:1 dr and 98% ee). The tert -butyl sulfonamide functionality of catalyst 10 is speculated to play crucial roles in the transition state as both bulky group and hydrogen-bond acceptor. Application of a representative Michael adduct has been also studied and proven to be useful for the diversity-oriented synthesis of enantiopure multiring heterocycles through a unique common bicyclic nitrone intermediate.

An overview of syntheses and chemical properties of polyfluoroalkyl 2 H - and 4 H -thiopyrans, their hydrogenated (3,4- and 3,6-dihydrothiopyrans, and tetrahydrothiopyrans) and S-oxidized derivatives is presented. The first part is devoted to the synthetic methods starting from acyclic or cyclic precursors, and on multicomponent reactions. The second one deals with the chemical properties of thiopyran derivatives such as elimination reactions, [4+2] cycloadditions, sulfur or C C double bond oxidations, and reactions with nucleophiles. The last part is focused on the biological evaluation of polyfluoroalkyl 2 H -thiopyrans, especially as potential cardiotonic agents.

Synthesis of a phosphonopentapeptide enkephalin analogue was achieved from heterocyclic aminophosphonates via the coupling of Boc-Tyr-Gly-Gly-OH with phosphonodipeptide. The latter was formed by coupling Boc-Phe-OH with N-terminal α,α-disubstituted heterocyclic α-aminophosphonates. GRAPHICAL ABSTRACT

A whole family of annelated 4H-thiopyran-4-ones as the core structural unit was readily synthesized in good yields by a microwave-assisted coupling-addition-S(N)Ar (CASNAR) sequence starting from readily available (het)aroyl chlorides, alkynes and sodium sulfide nonahydrate in a consecutive one-pot three-component reaction. All representatives display a pronounced halochromicity of the absorption bands upon protonation. According to DFT calculations, the electronic ground state of the annelated 4H-thiopyran-4-ones possess a considerable zwitterionic character.

An investigation regarding the synthesis of 2H-thiopyran compounds from substituted benzaldehydes with sodium sulfide (Na2S·10H2O) in aqueous ethanol was carried out. The structural elucidation of the products was performed by spectroscopic methods and in one example as X-ray crystallographic analysis. A plausible mechanistic pathway is also proposed that is entirely different from an earlier report.

1-(5,6-Dihydro-2H-thiopyran-2-yl)uracil derivatives, a new 4′-thio-D4-nucleoside analogue, were synthesized by reacting 5,6-dihydro-2H-thiopyran sulfoxide and persilylated uracil in a Pummerer-type thioglycosylation reaction. The reaction of 5-alkyl substituted dihydrothiopyran sulfoxide 7 only gave 1-(dihydrothiopyran-2-yl)uracil 9. On the other hand, the reaction with a 5-siloxy substituted derivative of 7 resulted in a mixture of products with the uracil moiety at either the α- or the γ-position. The use of a prolonged reaction time resulted in the exclusive formation of the 4-substituted dihydrothiopyran derivative 10. The result suggests that an equilibrium is operative in the formation of the α- and γ-adducts and that the latter should be more thermodynamically stable than the former. This conclusion was also supported by theoretical calculations.

A detailed study on the cycloaddition reactions of cross-conjugated enaminones 1 and 9 with dimethyl acetylenedicarboxylate (DMAD) and ketenes is described. The reactions provide a variety of pyran (4, 11), pyran-2-one 14 and pyrrol-3-ylidene 8 derivatives having great pharmacological and medicinal significance. Moreover, the preferred formation of product 8 over 7 has been explained on the basis of molecular dynamics (MD) simulations performed on the intermediate 5 in the gas phase. The synthetic potential of enaminones 9 has further been explored by treating them with Lawesson's reagent (LR) and trapping the in situ generated enaminothiones 16 with some acrylates 17 leading to the formation of thiopyran derivatives 19. To the best of our knowledge, this is the first report in which cross-conjugated enaminothiones 16 have been utilized in cycloaddition reactions.

(1 E ,3 Z )-1-Aryl-4-methanesulfonyl-2-nitro-1,3-butadienes ( 8 ), derived from the initial ring-opening of 3-nitrothiophene ( 5 ), have been found to undergo a facile base-induced cyclization leading to thiopyran S , S -dioxides ( 9 ), thus furnishing a further example of effective ring-enlargement from 5- to 6-membered sulfur heterocycles. Compounds 9 are obtained as single racemic mixtures in satisfactory yields; they still contain a nitrovinylic moiety, which can be exploited for further modifications targeted to new derivatives endowed with either synthetic or pharmacological potentialities e.g., in the field of L-type Ca 2+ -channel blockers.

Two (3,6-dihydro-2-methylsulfanyl-2 H -thiapyran-2-yl)phosphonate derivatives have been chemoselectively oxidized on the thiopyran sulfur. The obtained allylic six-membered cyclic sulfoxides 2a and 2b were reacted under Pummerer reaction conditions leading to new thiopyran derivatives ( 4a and 6b , respectively). In both studied cases, the nucleophilic attack of β,γ-unsaturated thionium ion intermediate took place regioselectively at the γ-position (even when occupied by a methyl substituent like in 2b ). An unexpected second product 7b was however obtained from substrate 2b (having the dimethyl-substituted double bond). Dephosphorylation of 7b under basic conditions led to an original conjugated tri-unsaturated trifluromethylcarbonyl thiopyran product ( 8b ). These results represent new original examples of the Pummerer reaction.

Some novel N(1)-arylidene-N(2)-cis-2,6-diphenyltetrahydrothiopyran-4-one azine derivatives were synthesised and their antibacterial activity against Streptococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and antifungal activity against Candida-6, Candida-51, Aspergillus niger, and Aspergillus flavus were evaluated.

The stereochemical aspects and photochemistry of a series of 2,4,4,6-tetrasubstituted-4 H -thiopyran-1-oxides are described. Substitution-induced changes to the sulfinyl group stereomutation and the ring conformation are investigated. The sulfoxides were configurationally stable at a wide thermal range, but underwent photocatalysed stereomutation at sulfur without concomitant isomerization at C-4. In almost all cases the trans isomer predominated at equilibrium. The theoretical studies are in close agreement with experimental results.

Reaction of 2-alkyl-4,5-dichloropyridazin-3(2H)-ones with p-cyanophenol and 2-mercaptopyrimidine in the presence of base gave 2,4,5-trisubstituted-pyridazin-3(2H)-ones 4–9 , 2-(4-cyanophenoxy)pyrimidine ( 10 ) and 5-cyano-5-(pyrimidin-2-yl)-2,7-dialkyl-5H-dipyridazino[4,5-b:4,5-e]-4H-thiopyran-1,6-diones 11 as a novel heterocycle.

A solvent-free reduction of 2,4,6-triarylthiopyrylium with NaBH4/alumina is described. The regioselectivity of these reductions were compared with those obtained in solution experiments.

On heating with alkynes, the readily prepared 1,3-dithioles 3 undergo a new cycloaddition reaction and an unprecedented molecular rearrangement with loss of chlorine to give the first 7H-thieno[2,3-c]thiopyran-7-thiones 4 and 4H-thieno[3,2-c]thiopyran-4-thiones 5 whose structures were confirmed by X-ray diffraction. Unexpectedly, the different alkynes used to form 3 and to convert it into 4 and 5 were incorporated regiospecifically into the thiophene and thiopyran rings, respectively. [reaction: see text]

The syntheses of ethyl (E)-4-[(2,3-dihydro-2,2,4,4-tetramethyl-2H-1-benzo[b]thiopyran-6-yl)-1-propenyl]-2-methylbenzoate (1) and (E)-4- [(2,3-dihydro-2,2,4,4-tetramethyl-2H-1-benzo[b]thiopyran-6-yl)-1-pro- penyl]-2-methylbenzoic acid (2) have been achieved. In comparison to ester 1, acid 2 exhibited greater efficacy in activating RARα, RARβ, and RARγ as well as greater potency in activating RARα and RARβ. Interestingly, both the ester 1 and acid 2 exhibited nearly equal potency in activating RARγ. Both compounds also induced tissue transglutaminase (TGase) activity approximately 50% of the level induced by trans-retinoic acid. An X-ray diffraction analysis of (E)- 2 revealed the aryl rings as nearly orthogonal [74, [2] ] and a torsional angle of 46.5(2)° between the thiochroman group and the propenyl group. Conjugation between such groups may not be a stringent requirement for receptor activation.

Proline-catalyzed enantioselective direct intermolecular aldol reactions of tetrahydro-4H-thiopyran-4-one with various aldehydes give anti adducts with high diastereo- and enantioselectivities in moderate to excellent yields. With the aromatic aldehydes best results were obtained in wet DMF whereas dry DMSO generally was superior with the aliphatic aldehydes. Desulfurization of the adducts with Raney Ni provides products equivalent to aldols from 3-pentanone with potential applications in polypropionate synthesis.

3-Chloro-2-phenyl-6-p-tolyl and 3-chloro-2,6-di-p-tolyl-4H-thiopyran-4-ones have been synthesized in moderate yieldes from the reaction of 3-chloro-tetrahydrothiopyran-4-ones with phosphorus pentachloride. Their thiones, oximes, and hydrazones have been also prepared. Treatment of thiones with malononitrile gave the corresponding 3-chloro-4-thiopyrylidenemalononitriles which gave 3-chloro-spirothiopyran derivatives of pyrazole, isoxazole, 1,3-thiazines when treated with hydrazine hydrate, hydroxylamine hydrochloride, thiourea and thiosemicarbazide, respectively. While treatment of 3-chloro-thiopyrylidene-malononitriles with acetylacetone gave the corresponding 3-chloro-spirothiopyran derivatives of pyran.

Combinatorial libraries of N-acylated 5-(S)-aminomethyloxazolidinone derivatives of S-oxide and S,S-dioxide tetrahydro-4(2H)-thiopyranyl and thiomorpholine phenyloxazolidinone series have been synthesized on a solid phase and evaluated for antimicrobial activity. Several novel potent leads have been identified, including orally active oxazolidinones with enhanced activity against respiratory tract infection pathogens Haemophilus influenzae and Moraxella catarrhalis.

6-aryl-2-morpholin-4-yl-4H-pyran-4-ones and 6-aryl-2-morpholin-4-yl-4H-thiopyran-4-ones were synthesised and evaluated as potential inhibitors of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). Several compounds in each series exhibited superior activity to the chromenone LY294002, and were of comparable potency to the benzochromenone NU7026 (IC(50)=0.23 microM). Importantly, members of both structural classes were found to be selective inhibitors of DNA-PK over related phosphatidylinositol 3-kinase-related kinase (PIKK) family members. A multiple-parallel synthesis approach, employing Suzuki cross-coupling methodology, was utilised to prepare libraries of thiopyran-4-ones with a range of aromatic groups at the 3'- and 4'-positions on the thiopyran-4-one 6-aryl ring. Screening of the libraries resulted in the identification of 6-aryl-2-morpholin-4-yl-4H-thiopyran-4-ones bearing naphthyl or benzo[b]thienyl substituents at the 4'-position, as potent DNA-PK inhibitors with IC(50) values in the 0.2-0.4 microM range.

1,5-Diphenyl-3,3-dicyano-1,5-pentanedione has been used to incorporate N, O, S to obtain 1,4-dihydropyridine, 4 H -pyran, and 4 H -thiopyran, which in turn serve as precursors for the synthesis of novel spiro heterocycles. All the compounds were characterized by IR and NMR spectral data.

The reaction of compound 1 with CS 2 and different active halo compounds gave the corresponding thiophene derivatives 2a,b-4a,b , whereas treatment of compound 1 with CS 2 and active methylene compounds afforded the corresponding thiopyran derivatives 5a,b , 6a,b , 7 , and 8 . Also, 1,3-thioxane derivatives 9 and 10 were obtained by reacting compound 1 with CS 2 and different cycloalkanones. Thiophene and pyrrolidene derivatives 11 , 12a,b , and 13a,b were obtained by reacting compound 1 with phenyl isothiocyanate and different halo compounds. The active methylene compounds and/or cycloalkanones were treated with compound 1 in the presence of phenyl isothiocyanate to give pyridines, thiopyran and oxazine derivatives 14a,b-16a,b , 17a-19a , and 19b , respectively.

Nine new molecular motors, consisting of a 2,3-dihydro-2-methylnaphtho[2,1-b]thiopyran or 2,3-dihydro-3-methylphenanthrene upper part and a (thio)xanthene, 10,10-dimethylanthracene, or dibenzocycloheptene lower part, connected by a central double bond, were synthesized. A single stereogenic center, bearing a methyl substituent, is present in each of the motors. MOPAC93-AM1 calculations, NMR studies, and X-ray analysis revealed that these compounds have stable isomers with pseudoaxial orientation of the methyl substituent and less-stable isomers with pseudoequatorial orientation of the methyl substituent. The photochemical and thermal isomerization processes of the motors were studied by NMR and CD spectroscopy. The new molecular motors all show two cis-trans isomerizations upon irradiation, each followed by a thermal helix inversion, resulting in a 360 degrees rotation around the central double bond of the upper part with respect to the lower part. The direction of rotation is controlled by a single stereogenic center created by the methyl substituent at the upper part. The speed of rotation, governed by the two thermal steps, was adjusted to a great extent by structural modifications, with half-lives for the thermal isomerization steps ranging from t(1/2)(theta) 233-0.67 h. The photochemical conversions of two new motors proceeded with near-perfect photoequilibria of 1:99.

The synthesis of cis- and trans -6-(trifluoromethyl)-3,4-dihydro-2 H -thiopyran-3,4-diols from 6-(trifluoromethyl)-2 H -thiopyran via an OsO 4 -catalysed dihydroxylation and bromohydroxylation–alkaline hydrolysis sequence is described. Acetylation of the diols followed by S -oxidation affords the corresponding cis- and trans -3,4-diacetoxy-6-(trifluoromethyl)-3,4-dihydro-2 H -thiopyran S-oxides which reacted with acetic anhydride and boron trifluoride diethyl ether complex by an additive Pummerer pathway giving tetraacetyl derivatives of trifluoromethyl-containing thiopyranoses.

4-Dimethylamino-5,6-dihydro-2 H -thiopyran-2-thiones were converted to 4-anilinodihydropyridine-2(1 H )-thiones in several steps. The latter were alkylated giving a mixture of isomeric methylthioderivatives which were hydrogenated with Raney nickel yielding 2-alkyl- and 2-aryl-substituted 4-anilinopiperidines. The configurations as well as the conformations of the formed diastereoisomers are investigated by means of NMR.

Ab initio theory and density functional theory (B3LYP) have been used to calculate the geometry optimized structures, configurational isomer energy differences (Δ E ), and the configurational enthalpies (Δ H 0 ), entropies (Δ S 0 ), and free energies (Δ G 0 ) of 4-alkyl equatorial tetrahydro-2 H -thiopyran-1-oxides (tetrahydrothiopyran-1-oxides, thiacyclohexane-1-oxides, thiane-1-oxides (Me, Et, neo -Pent, i -Pr, tert -Bu) and 4-trimethylsilyl equatorial tetrahydro-2 H -thiopyran-1-oxide. The calculated structural data indicate that repulsive steric interactions between the axial alkyl group and the ring atoms are the major contributors to the equatorial preference. The configurational isomer energy differences (Δ E ), configurational enthalpies (Δ H 0 ) and free energies (Δ G 0 ) of the 4-alkyl equatorial tetrahydro-2 H -thiopyran-1-oxides have been compared with the reported experimental conformational enthalpies (Δ H 0 ) and free energies (Δ G 0 ) of the corresponding alkylcyclohexanes and 4-alkyltetrahydro-2 H -thiopyrans. The use of the configurational isomer energy differences (Δ E ) and/or configurational free energies (Δ G 0 ) of 4-alkyl equatorial tetrahydro-2 H -thiopyran-1-oxides as possible models for assigning the difference in the steric requirements of an alkyl substituent in axial and equatorial positions is also discussed.

Ab initio molecular orbital theory with the 6-31G(d), 6-31+G(d), 6-31G(d,p), and 6-31G(2d) basis sets has been used to calculate the geometry optimized structures and the relative energies (Δ E ) of the rotamers of the chair conformers of 3-substituted equatorial tetrahydro-2 H -thiopyran-1-oxides (tetrahydrothiopyran-1-oxides, thiacyclohexane-1-oxides, thiane-1-oxides; CH 3 , CF 3 , CHO, COCH 3 , CN, F, Cl, Br). The conformational free energies (Δ G °) and relative energies (Δ E ) of the conformers and rotamers are discussed in terms of the repulsive nonbonded interactions in both conformers.

Ab initio MO calculations were carried out in 2-chloro-6-NR2-pyran-4-ones, 2-chloro-6-NR2-thipyran-4-ones and in their protonated forms with the aim of discussing the electronic and structural effects modulating the rotational barriers about the C–N partial double bond measured in previous research. The barriers in these molecules depend on NR2 substituents (pyrrolidino, dimethylamino, piperidino and morpholino groups were examined), on the O/S atoms in the pyranone/thiopyranone rings and differ in neutral and protonated forms. The results of calculations, carried out at different levels of theory (HF/6-31G∗//HF/6-31G∗, HF/6-31G∗∗//HF/6-31G∗∗, B3LYP/6-31G∗∗, MP2/6-31G∗∗/MP2/6-31G∗∗) and simulating the effect of a solvent (self-consistent isodensity polarized continuum model) were employed to analyse the effect of the different molecular fragments on the barrier to internal rotation about the partial C–N double bond. Parallel trends are found for calculated and experimental results as a function of changes in molecular structure even though the calculated barriers for the ions are overestimated.

Phosphonodithioformates are shown to be good heterodienophiles in [4+2] cycloadditions with open chain and cyclic dienes. Lewis acids efficiently catalyze this hetero Diels–Alder reaction and a selective radical desulfanylation of the cycloadducts using Bu 3 SnH leads to new (3,6-dihydro-2 H -thiopyran-2-yl) phosphonates.

[formula: see text] Aldol reaction of tetrahydro-4H-thiopyran-4-one with racemic 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde is easily controlled to give the 2,3-anti-3,4-syn or the 2,3-syn-3,4-syn adduct. Aldol homologations of these beta-hydroxy ketones with the same aldehyde occur with considerable mutual kinetic enantioselection (MKE) and, in each case, selectively give one of the eight possible diastereomers. Similar reactions of related beta-methoxy ketones are also very diastereoselective but proceed without significant MKE, resulting in two diastereomers. The adducts can be used for polypropionate synthesis.

Synthesis and photoisomerization of the new sulfone derivative 1c is described. Upon photolysis at 254 nm the sulfone 1c, unlike those of the model compound 1b and the other 2,4,4,6-tetraarylsubstituted sulfone derivatives, undergoes rearrangement in high regioselectivity to the bicyclic photoproduct 2c. The isolation of bicyclic photoproducts 2b and 2c under our experimental conditions led us to determine the molar ratios of these species during the transformations using HPLC.

Cyanothioacetamide (1) reacted with α- and β-naphthaldehyde 2a,b to afford the corresponding 3-naphthyl-2-thiocarboxamidopropenonitriles 3a,b. Compounds 3a,b structures could be elucidated via their reactions with acrylonitrile, ethyl acrylate (4a,b). N-arylmaleimides 6a-c and ethyl acetoacetate (8). The isolated products could be represented as the thiopyran, thiopyranopyrrolidine and pyridinethione derivatives 5a-d, 7a-f and 9a,b respectively. Pyridinethiones 9a,b had been used as the starting materials in the present study in addition to the next ones to synthesize several new thienopyridines, pyridothienotriazine and pyridothienopyrimidines 12a-f, 15a,b, 16b, 17–19a,b respectively through their reactions with the corresponding reagents. All structures of the newly synthesized heterocyclic compounds were established on the basis of the data of IR, 1H NMR and elemental analyses.

The reactions of ethyl diazoacetate with a series of 2-substituted thiophenes in the presence of catalytic rhodium (II) acetate were examined. In the cases of 2-methylthiophene and 2-(trimethylsilyl)thiophene, cyclopropane and thiopyran products predominated while thiophene-2-thiol and 2-(methylthio)thiophene gave rise to thiopyrans and ethyl 2-(2-thienylsulfanyl)acetate. No reaction was apparent when 2-pyrrolidinothiophene was used. 2-Alkoxythiophenes, however, allowed for the production of a series of ethyl 6-alkoxy-6-thioxo-2, 4-hexadienoates. The mechanistic implications are discussed. The reactions of EDA with 2-substituted thiophenes and catalytic Rh2(OAc)4 produced cyclopropanes, thiopyrans and polyenes. Download : Download full-size image

A number of derivatives of 2-imino-5,6-dihydro-2 H -thiopyran have been obtained in fair to good yields by treating the adducts from the α-metallated dienes H 2 CCHCHC(M)X (X = OCH 3 or SCH 3 ) and isothiocyanates with a calculated amount of dilute acid.

cis-3-Chloro-2,6-diaryltetrahydro-4H-thiopyran-4-ones have been synthesised in moderate yields from the addition of hydrogen sulfide to 2-chloro-diarylideneacetone. Their derivatives, sulfones, oximes, sulfone oximes, hydrazones and azines have been prepared. The structure of the above compounds was identified from their spectral characteristics.

4,4′-Dichloro-3,3′-diquinolinyl sulfide 3 underwent ring closure reactions with divalent nucleophiles to pentacyclic heterocycles: dithiin 4, thiopyran 5, thiazine 6, oxathiin 7 and thiaselenin 8 in good yield (76–100%). The chemical shift of the H-1 and H-13 protons in 1H NMR spectra is a result of the interaction between these atoms and the Z-atom.