Sulfonyl Substituent Research Articles

The effect of compositions and combinations of the reactants upon the copolycondensation of isophthalic acid/terephthalic acid with a combination of hydroquinones and bisphenols by tosyl chloride/dimethylformamide/pyridine

AbstractCopolycondensation of isophthalic acid (IPA)/terephthalic acid (TPA) with various combinations of 2,2‐bis(4‐hydroxyphenyl)propane (BPA) and hydroquinones (HQs) or bisphenols (BPs) was conducted to study the effects of the compositions of IPA/TPA and of BPA/HQs or BPA/BPs upon the reaction. Different from homopolycondensation of each of diol components examined where most of the reaction was facilitated by lower contents of IPA at about 70 mol %, the copolycondensation was influenced by a combination of diol components. With chlorohydroquinone (ClHQ) or bis(4‐hydroxyphenyl)sulfone (BPS) having a polar chlorine or sulfonyl substituent, the reaction proceeded most satisfactorily at IPA/TPA = 30/70, whereas it was IPA/TPA = 50/50 for the reaction with nonpolar methyl substituted methylhydroquinone (MeHQ). The reaction with 2,2‐bis(3,5‐dichloro‐4‐hydroxyphenyl)propane (TC‐BPA), despite having polar chlorine substituents in TC‐BPA, was not affected by IPA/TPA compositions. Alternatively, from the viewpoint of the compositions of diol components, the reactions containing 30–50 mol % of HQs or BPS yielded better results except for the reaction of IPA/TPA = 70/30, in which higher contents of MeHQ was more favorable. On the basis of sequence distributions of diol components in the resultant copolymers determined by NMR, compositions of IPA/TPA or diol components and combinations of the diols producing random copolymers yielded better results in copolycondensation. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1100–1106, 2004

Regioselectivity and the nature of the reaction mechanism in nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates with primary amines.

Second-order rate constants have been measured for the reaction of 2,4-dinitrophenyl X-substituted benzenesulfonates with a series of primary amines. The nucleophilic substitution reaction proceeds through competitive S-O and C-O bond fission pathways. The S-O bond fission occurs dominantly for reactions with highly basic amines or with substrates having a strong electron-withdrawing group in the sulfonyl moiety. On the other hand, the C-O bond fission occurs considerably for the reactions with low basic amines or with substrates having a strong electron-donating group in the sulfonyl moiety, emphasizing that the regioselectivity is governed by both the amine basicity and the electronic effect of the sulfonyl substituent X. The apparent second-order rate constants for the S-O bond fission have resulted in a nonlinear Brønsted-type plot for the reaction of 2,4-dinitrophenyl benzenesulfonate with 10 different primary amines, suggesting that a change in the rate-determining step occurs upon changing the amine basicity. The microscopic rate constants (k(1) and k(2)/k(-)(1) ratio) associated with the S-O bond fission pathway support the proposed mechanism. The second-order rate constants for the S-O bond fission result in good linear Yukawa-Tsuno plots for the aminolyses of 2,4-dinitrophenyl X-substituted benzenesulfonates. However, the second-order rate constants for the C-O bond fission show no correlation with the electronic nature of the sulfonyl substituent X, indicating that the C-O bond fission proceeds through an S(N)Ar mechanism in which the leaving group departure occurs rapidly after the rate-determining step.

Synthesis, Enantiomeric Conformations, and Stereodynamics of Aromatic ortho‐Substituted Disulfones

AbstractAromatic ortho‐disulfone derivatives are readily accessible from diiodide precursors by CuI‐mediated reaction with sodium sulfinate salts (DMF, 110°). The sulfonyl substituents adopt in solution and in the solid state two enantiomeric conformations (λ and δ) as evidenced by 31P‐ and 1H‐NMR data of the chiral D3‐symmetric tris{4,5‐bis[(4‐methylphenyl)sulfonyl]benzene‐1,2‐diolato(2−)‐κO,κO′}phosphate(v) anion (3a) and 1,2‐bis(camphor‐10‐sulfonyl)‐4,5‐dimethoxybenzene ((=1,2‐bis{{[(1S,4R)‐7,7‐dimethyl‐2‐oxobicyclo[2.2.1]hept‐1‐yl]methyl}sulfonyl}‐4,5‐dimethoxybenzene; 6c). X‐Ray structure analysis of 1,2‐dimethoxy‐4,5‐bis(methylsulfonyl)benzene (6a) and 1,2‐dimethoxy‐4,5‐bis(4‐methylphenyl)sulfonyl]benzene (6b) confirmed in the solid state the preferred chiral orientation of the sulfonyl groups. Dynamic conformational isomerism was detected for 6c in its 1H‐NMR in the temperature range of 110°, the corresponding free energy being 19.8 kcal⋅mol−1.

1,2-Bis[1-phenylsulfonyl-3-(phenylthio)indol-2-yl]ethene

The title compound, C42H30N2O4S4, crystallizes in the space group P\overline 1 with half a mol­ecule in the asymmetric unit and the other half generated by an inversion centre. The indole moiety is planar within \pm0.043 (1) Å. The dihedral angle between the indole system and the thio­phenyl ring is 83.4 (1)°. The S atom of the sulfonyl substituent has a distorted tetrahedral geometry. The molecular structure is stabilized by C—H⋯O and C—H⋯S interactions and the packing of the mol­ecules in the solid state is stabilized by C—H⋯O, C—H⋯π and π–π intermolecular interactions.

Trimethyl[3-methyl-1-(o-tolenesulfonyl)indol-2-ylmethyl]ammonium iodide and benzyl[3-bromo-1-(phenylsulfonyl)indol-2-ylmethyl]tolylamine.

The title compounds, C(20)H(25)N(2)O(2)S(+).I(-), (I), and C(29)H(25)BrN(2)O(2)S, (II), respectively, both crystallize in space group P-1. The pyrrole ring subtends an angle with the sulfonyl group of 33.6 degrees in (I) and 21.5 degrees in (II). The phenyl ring of the sulfonyl substituent makes a dihedral angle with the best plane of the indole moiety of 81.6 degrees in (I) and 67.2 degrees in (II). The lengthening or shortening of the C-N bond distances in both compounds is due to the electron-withdrawing character of the phenylsulfonyl group. The S atoms are in distorted tetrahedral configurations. The molecular structures are stabilized by C-H.O and C-H.I interactions in (I), and by C-H.O and C-H.N interactions in (II).

Ethyl β-{2-[4-(dimethylamino)phenyliminomethyl]-1-(phenylsulfonyl)indol-3-yl}acrylate

The title compound, C(28)H(27)N(3)O(4)S, crystallizes in the centrosymmetric space group P2(1)/n, with one molecule in the asymmetric unit. In the indole ring, the dihedral angle between the fused rings is 3.6 (1) degrees. The phenyl ring of the sulfonyl substituent makes a dihedral angle of 79.2 (1) degrees with the best plane of the indole moiety. The phenyl ring of the dimethylaminophenyl group is orthogonal to the phenyl ring of the phenylsulfonyl group. The dihedral angle formed by the weighted least-squares planes through the pyrrole ring and the phenyl ring of the dimethylaminophenyl group is 7.8 (1) degrees. The molecular structure is stabilized by C-H.O and C-H.N interactions.

1,2-Bis(1-phenylsulfonyl-3-phenylthioindol-2-yl)ethane

In the title compound, C42H32N2O4S4, the dihedral angle between the fused rings is 1.4 (1)°. The phenyl ring of the sulfonyl substituent makes a dihedral angle of 75.7 (1)° and the phenyl ring attached to the sulfide S atom makes a dihedral angle of 70.6 (1)° with the best plane of the indole ring. The molecular structure is stabilized by C—H⋯O hydrogen bonds.

Asymmetric conjugate additions to chiral α,β-unsaturated oxazolines with sulfonyl carbanions

Addition of sulfonyl carbanions with or without an electrophilic tether has been shown, under certain conditions, to add to α,β-unsaturated oxazolines in good yields and high de's. When 4-bromobutylsulfonyl carbanions are added to unsaturated oxazolines, three contiguous stereocenters are formed and good yields of 1,2,3-substituted cyclohexanes are obtained as a 5:1 mixture of only two diastereomers. The sulfonyl substituent may be reductively cleaved to form selectively 1,2-disubstituted cyclohexanes.

N-Methyl-N-(1-phenylsulfonylindol-2-ylmethyl)aniline.

In the title compound, 2-[(methylphenylamino)methyl]-1-(phenylsulfonyl)indole, C22H20N2O2S, the indole system is not strictly planar and the dihedral angle between the fused rings is 2.7 (1) degrees. The angles around the S atom of the sulfonyl substituent deviate significantly from the ideal value for tetrahedral geometry. The pyramidalization at the indole N atom is very small. Of the two C-H...O interactions, one influences the orientation of indole with respect to the sulfonyl group and the other determines the orientation of the phenyl bound to sulfonyl. The phenyl ring of the sulfonyl substituent makes a dihedral angle of 89.6 (1) degrees with the best plane of the indole. The molecular packing is stabilized by C-H...pi and C-H...O hydrogen bonds.

Electron acceptors of the fluorene series. 10.(1) novel acceptors containing butylsulfanyl, butylsulfinyl, and butylsulfonyl substituents: synthesis, cyclic voltammetry, charge-transfer complexation with anthracene in solution, and X-ray crystal structures of two tetrathiafulvalene complexes

2,4,5,7-Tetranitro-9-fluorenone (1b) reacts readily with n-butanethiol in dipolar aprotic solvents with selective substitution of nitro groups by butylsulfanyl groups in positions 2 and 7 (2, 3); the 2,5-isomer 4 was formed only as a minor product (<1%). Condensation of fluorenones 2-4 with malononitrile yielded 9-dicyanomethylene derivatives 5-7, which showed strong intramolecular charge transfer (lambda approximately 510-560 nm) and were found to sensitize the photoconductivity of carbazole-containing polymer films. Oxidation of sulfides 2-4 gave sulfoxide 8 or sulfones 9-11, which then were converted into their corresponding dicyanomethylene derivatives 12-15. All these novel acceptors showed three reversible single-electron reduction waves (cyclic voltammetry) yielding radical anion, dianion, and radical trianion; moreover, acceptors 13-15 showed also a fourth reduction wave, representing reversible tetraanion formation. Substitution of the oxygen of the carbonyl group in the fluorenones by a dicyanomethylene group increased the thermodynamic stability (K(SEM) growth) of the radical anion; K(SEM) ranged from 3 x 10(5) to 3 x 10(9) M(-1). CV measurements characterize compounds 3, 4 (EA = 1. 86-1.89 eV) as poor acceptors, 2, 6-11 (EA = 2.13-2.31 eV) as moderate acceptors, and 5, 12-15 (EA = 2.53-2.66 eV) as strong electron acceptors. Charge-transfer complex (CTC) formation between acceptors 9, 10, 13, 14, and anthracene as a donor was monitored by the appearance of additional low-energy bands in the visible region (CTC bands) of their electron absorption spectra. Increasing the EA of the acceptors from 9-fluorenones to the corresponding 9-dicyanomethylenefluorenes increases the complexation constants K(CTC) by 2.5-3 times, while sulfonyl substituents present substantial steric hindrance for complexation (as compared to the nitro group), decreasing K(CTC) values. Two CTCs for acceptors 14 and 17 with tetrathiafulvalene (TTF) were obtained, and their structures were solved by single-crystal X-ray diffractometry, giving the stoichometries 14:TTF, 2:3, and 17:TTF:PhCl, 1:1:0.5. In the former complex the packing motif is a mixed.DDAD'A. stack; in the latter complex the D and A moieties form unusually close CT pairs, which pack in a herringbone motif.

5,6-Dihydropyran-2-ones possessing various sulfonyl functionalities: potent nonpeptidic inhibitors of HIV protease.

On the basis of previous SAR findings and molecular modeling studies, a series of compounds were synthesized which possessed various sulfonyl moieties substituted at the 4-position of the C-3 phenyl ring substituent of the dihydropyran-2-one ring system. The sulfonyl substituents were added in an attempt to fill the additional S(3)' pocket and thereby produce increasingly potent inhibitors of the target enzyme. Racemic and enantiomerically resolved varieties of selected compounds were synthesized. All analogues in the study displayed decent binding affinity to HIV protease, and several compounds were shown to possess very good antiviral efficacy and safety margins. X-ray crystallographic structures confirmed that the sulfonamide and sulfonate moieties were filling the S(3)' pocket of the enzyme. However, the additional substituent did not provide improved enzymatic inhibitory or antiviral activity as compared to the resolved unsubstituted aniline. The addition of the sulfonyl moiety substitution does not appear to provide favorable pharamacokinectic parameters. Selected inhibitors were tested for antiviral activity in clinical isolates and exhibited similar antiviral activity against all of the HIV-1 strains tested as they did against the wild-type HIV-1. In addition, the inhibitors exhibited good antiviral efficacies against HIV-1 strains that displayed resistance to the currently marketed protease inhibitors.

Enantiomerically pure 2-piperazinemethanols as novel chiral ligands of oxazaborolidine catalysts in enantioselective borane reductions

Abstract Novel enantiomerically pure 2-piperazinemethanols ( 3–5 ) were synthesized from 2-piperazinecar☐ylic acid 1 . The asymmetric reduction of aromatic ketones, ketimine and oxime ether has been performed with reagents prepared from 2-piprazinemethanol and borane to yield enantiomerically enriched alcohols and amines, respectively. The preferred absolute configuration of the product was dependent on the structure of the sulfonyl substituent in the chiral ligand.

Homology modeling of gelatinase catalytic domains and docking simulations of novel sulfonamide inhibitors.

Three-dimensional models for the catalytic domain of gelatinases (MMP-9 and -2) have been constructed based on the X-ray crystal structure of MMP-3. Conformations of the loop segment which forms the bottom half of the S1' subsite but shows conformational diversity among the crystal structures of other MMPs have been explored by simulated annealing of each gelatinase model complexed with two highly potent "probe" inhibitors. Representative catalytic domain models have been selected for each gelatinase from the set of generated conformations based on shape complementarity of the loop to the probe inhibitors. The single model selected for MMP-9 was utilized to explain the structure-activity relationship of our novel sulfonamide inhibitors. Molecular dynamics (MD) simulations of the complex models revealed important features of the binding mechanism of our inhibitors: (i) the ligand carboxylate group coordinating to the catalytic zinc ion and hydrogen bonding to the Glu219 side chain, (ii) one of the sulfonyl oxygens forming hydrogen bonds with the main chain NHs (Leu181 and Ala182), (iii) the sulfonyl substituent making extensive hydrophobic contact with the S1' subsite. The gauche conformation exclusively adopted by the sulfonamide C-N-S-C torsion plays an important role in achieving the third binding feature by properly directing the substituent into the S1' subsite. Improvement of the inhibitory activity according to straight elongation of the sulfonyl substituent was attributed to an increase of the hydrophobic contact between the substituent and the S1' subsite. Structural modifications which alter the straight shape of the substituent lead to deterioration of the activity. On the other hand, the two candidate models selected for MMP-2 differ in the bottom shape of the S1' subsite: one with a channel-like subsite and the other with a pocket-like subsite resembling that of the MMP-9 model. The bottom shape was experimentally probed by chemical synthesis of inhibitors having elongated sulfonyl substituents whose terminal alkyl groups were shown by MD simulations to protrude from the S1' subsite bottom into the solvent. Gelatinase assays of these inhibitors showed that elongation of the substituent significantly reduces activity against MMP-9 while retaining activity against MMP-2, consequently increasing the selectivity between MMP-2 and -9. The results confirm that MMP-9 has a pocket-like S1' subsite with a floorboard and MMP-2 has a channel-like S1' subsite.

What makes a neutral imino dieneophile undergo a thermal, non-catalysed, Diels-Alder reaction?

Ab initio calculations have been carried out at the MP2/6-31G ∗ level of theory on the aza-Diels-Alder reaction of a range electron deficient imines (with sulfonyl and/or carbonyl substituents) with buta-1,3-diene. In all cases but one, an early cyclic transition-state could be located in which most often, the forming NC bond was more fully formed than the forming CC bond. However, examples were found in which this order of bond formation was reversed. Examination of HOMO-LUMO energy levels show that aza-Diels-Alder reactions are HOMO (diene)-LUMO (dienophile) controlled and that the most electron deficient imines should be more reactive than simple alkyl or aryl imines and imines possessing less electron withdrawing groups. Evidence is also found for exo-lone pair effects, but these effects become obscured by other stereoelctronic effects as electron withdrawing substituents are added to the imine.

N-p-Amino- and N-p-nitro-phenylsulfonyl derivatives of dipeptides, a new family of ligands for copper(II). Potentiometric and spectroscopic studies

The co-ordination ability of four dipeptide analogues substituted on the N-terminal amino group with p-nitrophenylsulfonyl (nps-Ala-Ala and nps-Ala-His) and p-aminophenylsulfonyl (aps-Ala-Ala and aps-Ala-His) groups was studied by potentiometric and spectroscopic (UV/VIS absorption, CD and EPR) techniques. The N-terminal sulfonyl substituent drastically changes the acidity of the sulfonamide proton making nitrogen very efficient in binding to CuII. The sulfonamide nitrogen having pK between 9 and 11 does not need any anchoring binding group to form complexes with CuII. The para substituent on the phenyl ring (amino or nitro) influences very strongly the acidity of the sulfonamide proton. The nps or aps moieties change the co-ordination equilibria considerably when compared to the parent dipeptide Ala-His. Both groups enforce the formation of dimeric complexes, whereas in the case of the parent dipeptide the major species are only monomeric.

On the mechanism of thermal decomposition of 4‐alkyl‐5‐sulfonylimino‐Δ2‐1,2,3,4‐thiatriazolines

AbstractThe kinetics of the thermal decomposition of several sulfonyl substituted thiatriazolinimines 1a‐g were investigated in different solvents both in the presence and in the absence of trapping reagents. The first‐order rate constants observed in all cases, are dependent on the inductive effect of the sulfonyl substituent (R), as well as on solvent polarity, but independent on the nature and concentration of the co‐reagent. These results, and the low activation energy, are rationalized by assuming an anchimeric assistance of the sulfonyl group during thermolysis. This would give the intermediate 7, which collapses to the thiaziridinimine 2 before being trapped by the co‐reagent.

ChemInform Abstract: Synthesis and Biological Evaluation of New C(4) Heterofunctionalized Monocyclic β‐Lactams Derived from Penicillin G.

AbstractStarting from the thiazoline‐azetidinone (I), a useful chiral synthon derived from natural penicillin G, a variety of ca. 60 β‐lactams such as (II) possessing a thiocarbonyl or sulfonyl substituent as a potentially good leaving group are prepared by common methods and their antibiotic properties are tested; only (IIa) and (IIb) exhibit a weak antibacterial effect.

ChemInform Abstract: Comparison of the Effects of Sulfenyl, Sulfinyl, and Sulfonyl Substituents on Diene Reactivity and Regioselectivity in the Diels‐Alder Reaction.

ChemInform Abstract: Comparison of the Effects of Sulfenyl, Sulfinyl, and Sulfonyl Substituents on Diene Reactivity and Regioselectivity in the Diels‐Alder Reaction.

Synthesis and biological evaluation of new C (4) heterofunctionalized monocyclic β-lactams derived from penicillin G

A simple and practical methodology has been developed for the preparation of monocyclic β-lactams 6 derived from penicillin G, possessing a thiocarbonyl ( 6a) or a sulfonyl ( 6b) substituent at C(4) as potentially good leaving groups. Two phthalidyl ester pro-drugs, 34f (L = SO 2CH 2Ph) and 40f (L = SO 2CH 2COOH), exhibited very weak antibacterial properties in vitro. However, no activity as β-lactamase inhibitors was detected for the two families of 6.

ChemInform Abstract: Carbon Acidity. Part 70. Equilibrium Ion Pair Acidities in Tetrahydrofuran of Benzylic Carbon Acids Stabilized by an Adjacent Cyano, Carboalkoxy, and Sulfonyl Substituent. Delocalization and Aggregation of Ion Pairs.

AbstractThe pKa values of (I) are determined with the aid of transmetalation equilibria, using indicators such as (IV).