Sulfonyl Function Research Articles

Synthesis and structure activity relationship studies of 2‐amino‐4‐arylsulfonyl‐5,6,7,8‐tetrahydroquinazolines as 5‐HT6 receptor antagonists

AbstractA novel series of 4‐arylthio‐ or 4‐arylsulfonyl‐substituted 2‐amino‐5,6,7,8‐tetrahydroquiazolines was synthesized and evaluated for serotonin receptor subtype 6 (5‐HT6R) antagonistic effects in vitro. The structure activity relationships (SAR) of this series were discussed on the basis of in vitro activity. Among the derivatives synthesized in the present study, the lead compound, 7a, having sulfonyl functionality at the 4‐position and N‐methylpiperazine at the 2‐position of the core structure showed the most potent 5‐HT6 receptor inhibitory activity in vitro and good metabolic stability without CYP liability.

Radicals and Sulfur Dioxide: A Versatile Combination for the Construction of Sulfonyl-Containing Molecules.

Molecules containing a sulfonyl functionality, such as sulfones, sulfonyl chlorides or sulfonamides play an important role in organic chemistry and have found widespread application, especially in the construction of biologically active compounds. Recently, methods for the synthesis of the sulfonyl moiety utilizing sulfur dioxide as a key building block have received considerable attention. In this context, radical-based transformations with sulfur dioxide have emerged as a new and attractive approach for the construction of the sulfonyl functional group. This short review highlights recent advances in the use of sulfur dioxide in radical reactions and covers the historical background, which forms the basis for these current progresses. Limitations of the existing methods and potential further developments will be discussed.

1-(Benzenesulfonyl)-1,5-Dihydro-4,1-Benzoxazepine as a New Scaffold for the Design of Antitumor Compounds

Bozepinib is a potent and selective anticancer compound which chemical structure is made up of a benzofused seven-membered ring and a purine moiety. We previously demonstrated that the purine fragment does not exert antiproliferative effect per se. A series of 1-(benzenesulfonyl)-4,1-benzoxazepine derivatives were synthesized in order to study the influence of the benzofused seven-membered ring in the biological activity of bozepinib by means of antiproliferative, cell cycle and apoptosis studies. Our results show that the methyleneoxy enamine sulfonyl function is essential in the antitumor activity of the structures and thus, it is a scaffold suitable for further modification with a view to obtain more potent antitumor compounds.

Spectroscopic and structural properties of bisphthalonitriles with O/S/SO2 grafting: Comparative theoretical and experimental studies

Three bisphthalonitriles with different grafting functions (O/S/SO2) have been selected for their future interest in the preparation of dimeric phthalocyanines with tailored properties. The bisphthalonitrile derivatives have been prepared and comparatively characterized. Their complete structural properties were investigated and their XRD-determined structures were compared with their DFT-optimized ones. Molecular orbital levels and energy gaps were also determined and analysed. The sulfonyl (SO2) function induces different behaviour compared to the S and O grafting which are more similar.

ChemInform Abstract: Rhodium‐Catalyzed Direct ortho‐Alkenylation of Phenyl Sulfones with Alkynes Utilizing Sulfonyl Function as Modifiable Directing Group.

Abstract The ortho-selective alkenylation of phenyl sulfones with alkynes proceeds effectively in the presence of a cationic Cp*-rhodium(III) catalyst together with an appropriate carboxylic acid involving regioselective C–H bond cleavage directed by the sulfonyl function. An (ortho-alkenylated phenyl) methyl sulfone prepared by this hydroarylation method undergoes palladium-catalyzed α-arylation and subsequent diastereoselective cyclization to directly produce the corresponding thiochromane 1,1-dioxide derivatives.

One-Pot Synthesis of Allylic Sulfones, Ketosulfones, and Trifylallylic Alcohols from Domino Reactions of Allylic Alcohols with Sulfinic Acid under Metal-Free Conditions.

Invited for the cover of this issue is the group of Shun-Jun Ji and co-workers at Soochow University, (China). The image depicts a cheaper, low-toxic, eco-friendly benign and metal-free methodology incorporating the both aryl and trifyl sulfonyl functionality from allylic alcohols. Read the full text of the article at 10.1002/chem.201500469.

One-Pot Synthesis of Allylic Sulfones, Ketosulfones, and Triflyl Allylic Alcohols from Domino Reactions of Allylic Alcohols with Sulfinic Acid under Metal-Free Conditions.

A metal-free tandem procedure by using a sulfonylation reaction of aryl allylic alcohols followed by an iodobenzenediacetate (PIDA)-promoted oxidative functionalization has been established. Allylic sulfones, γ-ketosulfones, and triflyl allylic alcohols have been constructed in a single operation. The methodology incorporates the sulfonyl (both aryl and triflyl) functionality with a simple work-up procedure.

Rhodium-catalyzed direct ortho-alkenylation of phenyl sulfones with alkynes utilizing sulfonyl function as modifiable directing group

The ortho-selective alkenylation of phenyl sulfones with alkynes proceeds effectively in the presence of a cationic Cp*-rhodium(III) catalyst together with an appropriate carboxylic acid involving regioselective C–H bond cleavage directed by the sulfonyl function. An (ortho-alkenylated phenyl) methyl sulfone prepared by this hydroarylation method undergoes palladium-catalyzed α-arylation and subsequent diastereoselective cyclization to directly produce the corresponding thiochromane 1,1-dioxide derivatives.

Sulfonyl-bridged oligo(benzoic acid)s: synthesis, X-ray structures, and properties as metal extractants

Sulfonyl-bridged oligo(benzoic acid)s 7 n (n = 2–4) are prepared from the corresponding triflate esters (8 n ) of sulfur-bridged oligophenols by palladium-catalyzed methoxycarbonylation of the triflate moieties, followed by hydrolysis of the resulting methyl esters, and subsequent oxidation of the sulfur bridges. X-ray analysis reveals that dimer 7 2 forms supramolecular zig-zag chains through intermolecular hydrogen bonds between the carboxy groups. As for the crystal of trimer 7 3 , two molecules are associated through two couples of intermolecular hydrogen bonds between terminal and central carboxy groups to form a cyclic dimer, which connects with two adjacent dimers with the remaining carboxy groups to construct an infinite columnar structure. Tetramer 7 4 adopts a monomolecular cyclic structure through intramolecular hydrogen bonds between the terminal carboxy groups, and a molecule connects with each of two adjacent molecules through two couples of intermolecular hydrogen bonds between inner carboxy and sulfonyl groups. Solvent extraction experiments reveal that the oligo(benzoic acid)s exhibit high extractability toward lanthanoid ions (Ln3+); the performance follows the order 7 4 ≈ 7 3 > 7 2 . Moderate extraction selectivity is observed for the extraction of Pr3+, Gd3+, and Yb3+ with 7 2 . X-ray crystallographic analysis of cluster [Tb4L4(H2O)6](Et3NH)4, which was prepared from 7 4 (H4L) and Tb(NO3)3·6H2O in the presence of Et3N, reveals that no sulfonyl oxygens coordinate to the metal centers. This indicates that the high extractability of 7 4 originates from the electron-withdrawing nature of the sulfonyl function, which increases the acidity of two adjacent carboxy groups.

Controlled synthesis of branched polystyrene via RAFT technique in the presence of chain transfer monomer p-vinyl benzene sulfonyl chloride

Branched polystyrene was first obtained via a reversible addition-fragmentation chain transfer (RAFT) process in the presence of chain transfer monomer p-vinyl benzene sulfonyl chloride (VBSC) in benzene at 60 °C with 2-(ethoxycarbonyl)prop-2-yl dithiobenzoate as the RAFT agent and 2,2-azobisisobutyronitrile as an initiator. During the RAFT polymerization, VBSC played the role of branching agent. It could not only copolymerized but also acted as a chain transfer agent due to the polymerizable vinyl group and sulfonyl chloride chain transfer group in the VBSC. Gel permeation chromatography (GPC) traces demonstrated that the number-average molecular weights and molecular weight distributions increased along with monomer conversion. Compared with the RAFT process without VBSC, the resulting polymers had broad molecular weight distributions and the sulfonyl functionality of the resultant polymer at the branching point, indicating the formation of branched polystyrene. The structure of the obtained polystyrene was further analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. The findings indicated that the branched polystyrene was mainly formed via the RAFT copolymerization of VBSC and styrene firstly to form polystyrene bearing pendant sulfonyl chloride group, and then the pendant sulfonyl chloride group acted as the chain transfer agent to generate the branched structure. In addition, the degree of branching and VBSC unit in copolymer increased along with the VBSC in the feed, implying that composition and structure of the branched polystyrenes could be tuned by the amount of VBSC in the feed. Open image in new window

Dichloroketene-Induced Cyclizations of Vinyl Sulfilimines: Application of the Method in the Synthesis of (±)-Desoxyeseroline

The reactions of several aryl-, furanyl-, and vinyl-substituted sulfilimines with dichloroketene proceeded at 25 degrees C to yield thioalkyl-substituted gamma-lactams. The overall process involves nucleophilic addition of the nitrogen atom of the sulfilimine onto the highly electrophilic dichloroketene to first generate a zwitterionic intermediate. A subsequent [3,3]-sigmatropic rearrangement is followed by intramolecular trapping of the Pummerer cation by the amido anion to furnish the observed gamma-lactam product. Incorporation of donor groups on the aromatic ring of the sulfonyl functionality had little effect when aryl-substituted sulfilimines were used but exhibited a major effect on the efficiency of the reaction with furanyl-substituted systems. The placement of an electron donor group (i.e., OMe) on the sulfonyl aryl group enhances the nucleophilicity of the amido anion contained within the sulfonium ion intermediate and facilitates the rate of the 3,3-sigmatropic rearrangement. Styryl-substituted sulfilimines cyclize in a stereospecific manner and produce a 3:2-mixture of gamma-lactams and the isomeric imino-lactone system. The heavily functionalized gamma-lactams are easily converted to a variety of nitrogen containing substrates. The vinyl sulfilimine cyclization method was applied to the total synthesis of the Calabar alkaloid (+/-)-desoxyeseroline.

Effect of substituents on benzenesulfonyl motif of 4-phenyl-1-arylsulfonylimidazolidinones for their cytotoxicity.

To explore the effect of substituents' on phenyl motif on sulfonyl function of novel anticancer 4-phenyl-1-benzenesulfonylimidazolidinones (1), electron donating or withdrawing substituents were introduced at 3 or 4-position and the analogs were tested against human lung (A549) and colon (HCT-15) cancer cell lines. Quantitative structure activity relationship of the 4-substituted series shows that only STERIMOL L values are well correlated. The increment of substituent's volume enhances the activity against both cell lines. The small substituent at 3-position additionally increases the activity. However naphthyl group in place of phenyl reduces the activity. Therefore the phenyl motif with sterically large substituent at 4-position and small substituent at 3-position may be important for their activity. Integration of these substituents' effects into the structural design led to discover the more potent analog, 4-phenyl-1-(N-acetylindoline-5-sulfonyl) imidazolidinone (1n).

1H- and 13C-NMR studies on sulfinyl and sulfonyl derivatives of positional isomers of methyl thialaurate

Sulfoxidation of the positional isomers of methyl thialaurate with m-chloroperoxybenzoic acid gave the corresponding sulfinyl and sulfonyl derivatives. In the 1H-NMR spectroscopic analysis, the sulfoxide function exerted a weaker deshielding effect than the sulfone group on the chemical shift of the protons of the adjacent methylene groups. The shift of the protons of the unperturbed α-methylene groups adjacent to the sulfone and sulfoxide function appeared at δ 2.97 and 2.67, respectively. It was possible to identify 7 of the 10 sulfinyl and sulphonyl derivatives by 1H-NMR spectroscopy. In the 13C-NMR spectroscopic analysis, the effect of the sulfinyl and sulfonyl function on the chemical shift of the adjacent α- and β-methylene carbons was quite similar, but significant enough to permit further differentiation of positional isomers. The chemical shifts of the α- and β-methylene carbons located adjacent to the sulfinyl function appeared at about 52.2 and 22.5 ppm, respectively. In the case of sulfonyl derivatives the shift of the α and β-methylene carbon atoms were found at about 52.4 and 21.6 ppm. It was possible to identify each positional isomer of the sulfinyl and sulfonyl derivatives of methyl thialaurate by this technique.

ChemInform Abstract: POTENTIAL BIS‐ALKYLATING AGENTS FOR CANCER CHEMOTHERAPY. APPROACHES TO THE SYNTHESIS OF 2‐SULFONYL‐1,4‐BIS(DIMETHANESULFONOXY)BUTANES

AbstractNach drei Methoden werden Derivate (IV) von Myleran (XI) dargestellt, die in die Sulfonsäureester (X) übergeführt werden.

Potential bis-alkylating agents for cancer chemotherapy. Approaches to the synthesis of 2-sulfonyl-1,4-bis(dimethanesulfonoxy)butanes

Three general methods for the synthesis of derivatives of the bis-alkylating agent, myleran [1,4-bis(methane-sulfonoxy)butane (1)], are presented. These derivatives contain a lipophilic group attached to the 2 position of 1,4-bis(methanesulfonoxy)butane by means of a sulfonyl function. As examples of the scope of the methods, the synthesis of seven such derivatives (12a-g) is presented. All seven were inactive against L1210 and P388 leukemia in the mouse.

The intramolecular nucleophilic reaction of a phenolic hydroxyl group at the active site of papain

Sulfonylation of the sulfhydryl protease papain with β-(2-hydroxy-3,5-dinitrophenyl)ethanesulfonic acid sultone 1 at pH 5.2 and 25° gives a thiosulfonate species 2 , the desulfonylation of which has been studied. Recyclization to give the sultone 1 via the nucleophilic attack of the phenolic hydroxyl group in 2 on the sulfonyl function has been found to compete effectively with hydrolysis. This is the first case in which a recyclization reaction has been observed where the central atom of the newly generated nucleophilic group produced by the ring-opening reaction of a cyclic ester with a protease is different in kind from that present in the active site of the enzyme.

The Tracer Study of the Reaction of Diphenyl Sulfone-1-14C with Elemental Sulfur Using a Convenient Degradative Method

Abstract The reaction of diphenyl sulfone with elemental sulfur to give diphenyl sulfide and sulfur dioxide at above 300°C was investigated using diphenyl sulfone-1-14C. By the degradation of the product, diphenyl sulfide-x-14C, it was found that no migration of sulfide group took place. β-Naphthyl phenyl sulfone was also subjected to the same reaction, and not only β-naphthyl phenyl sulfide but also di-β-naphthyl sulfide and diphenyl sulfide were found among the products. These observations appear to indicate the reaction to be a rather simple displacement reaction that involves the initial attack of polymeric sulfur radical chain at C-1 bearing sulfonyl function.