Synthesis and Cytotoxicity of 3-(Hetarylthio)-1-propynyl(trimethyl)silanes

We have developed a two-step method for synthesis of 3-(hetarylthio)-1-propynyl(trimethyl)silanes from thiols in a phase-transfer catalysis system HCCCH₂Br-solid K₂CO₃-18-crown-6-toluene followed by reaction with n-BuLi-Me₃SiCl in ether or THF. We have observed that 3-[1,3-bis(trimethylsilyl)-2-propynyl]thioindole displays high cytotoxicity in HT-1080 and MG-22A tumor cell lines.     

Synthesis and Cytotoxicity of Derivatives of Di(3-indolyl) Selenide

A method has been developed for the synthesis of di(3-indolyl) selenides. From indole and SeO₂. N-Alkyl derivatives of di(3-indolyl) selenide have been obtained in the two-phase system alkyl halide–solid K₂CO₃ (or KOH)–18-crown-6–toluene. It was discovered that N-unsubstituted di(3-indolyl) selenides possess high cytotoxicity on HT-1080 and MG-22A tumor cell lines.     

Adiabatic and isothermal apparent molal compressibilities of organic compounds in water. I. Cyclic and open-chain secondary alcohols and ethers

The limiting apparent molal adiabatic and isothermal compressibilities in aqueous solutions of alcohols and ethers at various temperatures have been determined by means of ultrasonic velocity measurements. The following compounds have been considered: secondary cyclic and open-chain alcohols (cyclopentanol, cyclohexanol, cycloheptanol, 2-butanol, 3-pentanol, 3-hexanol, 4-heptanol; cyclic ethers of the types (CH₂)₃O_n (n=1, 2, 3), (CH₂)_nO₂ (n=3, 4, 5), and (CH₂)_nO (n=3, 4, 5); and the linear diethers dimethoxymethane, diethoxymethane, and 1,2-dimethoxyethane. The results indicate that both alcohols and ethers cause the water near the solute to become more resistant to pressure than the bulk. This is in agreement with the prediction of a mixture model for water.     

Stereoregulation in cationic polymerization by designed Lewis acids. II. Effects of alkyl vinyl ether structure

Stereoregulation in the cationic polymerization of various alkyl vinyl ethers was investigated with bis[(2,6‐diisopropyl)phenoxy]titanium dichloride ( 1 ; catalyst) in conjunction with the HCl adduct of isobutyl vinyl ether as an initiator in n‐hexane at −78 °C. The tacticities depended on the substituents of the monomers. Isobutyl and isopropyl vinyl ethers gave highly isotactic polymers (mm = 83%), whereas tert‐butyl and n‐butyl vinyl ethers resulted in lower isotactic contents (mm ∼ 50%) similar to those for TiCl₄, a conventional Lewis acid, thus indicating that the steric bulkiness of the substituents was not the critical factor in stereoregulation. A statistical analysis revealed that the high isospecificity was achieved not by the chain end but by the catalyst 1 or the counteranion derived therefrom. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1060–1066, 2001     

Synthesis of novel macrocyclic crown ethers from D-glucose

A simple and efficient synthetic protocol for an easy access of carbohydrate-linked crown ethers from cheap and readily available D-glucose in good yields has been devised. The base-mediated cyclization of sugar-linked bis-iodo podands in CH₃CN with amines, including ethylamine and furfurylamine afforded the novel chiral monoaza-15-crown-5-type macrocyclic crown ethers anellated to 3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose and 3-O-benzyl-1,2-O-isopropylidene-α-D-allofuranose. The glucose-based crown ethers have been characterized by spectroscopy techniques including IR, ¹H NMR, and ¹³C NMR.     

Controlled random and alternating copolymerization of (meth)acrylates,acrylonitrile, and (meth)acrylamides with vinyl ethers by organotellurium‐, organostibine‐, and organobismuthine‐mediated living radical polymerization reactions

Random and alternating copolymerizations of acrylates, methacrylates, acrylonitorile, and acrylamides with vinyl ethers under organotellurium‐, organostibine‐, and organobismuthine‐mediated living radical polymerization (TERP, SBRP, and BIRP, respectively) have been studied. Structurally well‐controlled random and alternating copolymers with controlled molecular weights and polydispersities were synthesized. The highly alternating copolymerization occurred in a combination of acrylates and vinyl ethers and acrylonitorile and vinyl ethers by using excess amount of vinyl ethers over acrylates and acrylonitorile. On the contrary, alternating copolymerization did not occur in a combination of acrylamides and vinyl ethers even excess amount of vinyl ethers were used. The reactivity of polymer‐end radicals to a vinyl ether was estimated by the theoretical calculations, and it was suggested that the energy level of singly occupied molecular orbital (SOMO) of polymer‐end radical species determined the reactivity. By combining living random and alternating copolymerization with living radical or living cationic polymerization, new block copolymers, such as (PBA‐alt‐PIBVE)‐block‐(PtBA‐co‐PIBVE), PBA‐block‐(PBA‐alt‐PIBVE), and (PTFEA‐alt‐PIBVE)‐block‐PIBVE, with controlled macromolecular structures were successfully synthesized. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Internal Nucleophilic Termination in Acid‐Mediated Polyene Cyclizations. Part 5

Treatment of the acyclic tetraenols (E)‐ and (Z)‐ 2 with an excess of ClSO₃H in 2‐nitropropane at ? 80° stereoselectively afforded in 30 and 43% yield, respectively, diastereoisomer mixtures of the racemic, tricyclic ethers 1c,d and 1a,b , together with 20 (Table). Under identical conditions, but with the acyclic pentaenol 10 (1 : 1 diastereoisomer mixture) as substrate, the tricyclic ethers 22a / 22b (10 : 1) were isolated in 27% yield. These kinetically controlled stereospecific transformations are thought to proceed via non‐concerted pathways (see Schemes 5 and 7), fully consistent with our earlier work. In contrast, another set of reaction conditions (CF₃CO₂H, CH₂Cl₂, ? 15° to ? 10°) was used for the cyclization of the monocyclic dienols (E)‐ 3 and (Z)‐ 3 , which resulted in the non‐stereoselective formation of the major products 1c,d and 1a,b , respectively, in 35–37% yield. Representing novel didehydro analogues of the known ambergris odorant (±)‐Ambrox^® and its diastereoisomers, the qualitative organoleptic properties of 1a – d and of the 10 : 1 diastereoisomer mixture of the novel tetradehydro analogues 22a / 22b are briefly described.     

Comparative photophysical behaviour of naphthalene-linked crown ethers and aza crown ethers of varying cavity dimensions

A comparative time-resolved emission studies of several naphtho-crown ethers I–V, where metal ions can be complexed in a predetermined orientation with respect to the naphthalene (Naph) π-plane and naphthalene-linked aza crown ethers (L1 and L2) have been presented. In both the systems, crown ethers and aza crown ethers, naphthalene fluorescence gets quenched. In the systems I to V, the quenching is mainly due to efficient spin-orbit coupling (SOC) leading to greater population of the lowest triplet state of naphthalene. This SOC depends on the orientation of the crown ring with respect to the Naph-π-plane. However, in the systems L1 and L2, the quenching is due to photoinduced electron transfer (PET) from nitrogen lone pair of the aza crown ring to naphthalene moiety and consequent exciplex formation. The results have been interpreted using the time-resolved emission studies of all the compounds in various solvents, their alkali metal ion complexes, and protonated ligands.     

Synthesis and complexing properties of double armed diaza‐15‐crown‐5 and diaza‐18‐crown‐6 ethers having 4′‐hydroxy‐3′,5′‐disubstituted benzyl groups

A series of double armed diaza‐15‐crown‐5 ethers (9a ‐ 16a) and diaza‐18‐crown‐6 ethers (9b ‐ 16b) have been prepared by the Mannich reaction of 2,6‐disubstituted phenols with the corresponding N,N'‐dimethoxymethyldiaza‐crown ethers in benzene. The crystal structures of the diaza‐18‐crown‐6 ethers having iso‐propyl (10b) , tert‐butyl (11b) , and mixed methyl and tert‐butyl groups (12b) at positions 3′ and 5′ of the phenolic side arms were determined using X‐ray diffraction methods. Competitive transport by these ligands for sodium, potassium and cesium cations were measured under basic‐source phase and acidic‐receiving phase conditions.     

Deoxy-nitrosugars. 6th communication. Stereoelectronic control in the reductive denitration of tertiary nitro ethers. A synthesis of ‘C-glycosides’

The separate, radical denitration with Bu₃SnH of the pyranose derivatives 3, 4, 9 , and 10 gave in good yields exclusively the ‘C-glycosides’ 5 and 11 , respectively (Scheme 1). Similar reduction of the cyclohexyl derivatives 15, 16, 19 and 20 gave 4:1 mixtures of 17, 18, 21 and 22 , respectively, always with predominant formation of an axial C,H-bond. In the furanose series a divergent behaviour was observed for the D -mannose-derived nitro ethers 25 and 27 and the D -ribose-derived nitro ethers 30 and 31 , respectively, in that the former two gave isomerically homogeneous reduction products ( 26 and 28 , respectively; Scheme 3) and the latter a 1:1 mixture of the diastereoisomers 32 and 33 (Scheme 4). The stereochemical results were explained on the basis of the stereoelectronic effect of the ring O-atom, the preferred conformation of the intermediate, pyramidal alkoxyalkyl radicals and steric effects in the trioxabicyclo [3.3.0]octane ring system.     

Modification of olefin polymerization catalysts. I. Mechanism of the interaction between AIEt3 and silyl ethers

The interaction between AlEt₃ and silyl ethers, Ph_nSi(OMe)_4-n (n = 0–3), was followed by ¹³C- and ²⁹Si-NMR techniques in conditions close to those typical for an olefin polymerization reaction with supported Ziegler–Natta catalysts (A1Et₃:silyl ether ratios from 1 to 10, temperature range 25–75°C). A1Et₃ and silyl ethers form instantaneously at ambient temperature a donor-acceptor complex, which is stable at a 1:1 molar ratio. In the presence of excess A1Et₃ the complex decomposes via a mechanism consisting, in the case of PhSi(OMe)₃, of five consecutive steps: alternating complexation and ether reductions with the formation of alkylated silyl ethers, Ph(Et)_nSi(OMe)_3-n (n = 1,2), and dialkyl-aluminum alkoxides, (Et₂A1OMe₃)_n (n = 2,3). The rate of decomposition was enhanced by the increasing number of methoxy groups present in the silyl ether, heating, or a high A1Et₃:silyl ether ratio. The decomposition was not inhibited by the presence of 1-hexene.     

Ruthenium(II)‐Catalyzed C−H Difluoromethylation of Ketoximes: Tuning the Regioselectivity from the meta to the para Position

A highly para‐selective C_Ar?H difluoromethylation of ketoxime ethers under ruthenium catalysis has been developed. A wide variety of ketoxime ethers are compatible with the reaction, which leads to the corresponding para‐difluoromethylated products in moderate to good yield. A mechanistic study clearly showed that chelation‐assisted cycloruthenation is the key factor in the para selectivity of the difluoromethylation of ketoxime ethers. Density functional theory was used to gain a theoretical understanding of the para selectivity.#     

Structure and reactivity of α,β-unsaturated ethers. XIII. Cationic copolymerization and acid-catalyzed hydrolysis of 1,2-dialkoxyethylenes

The cationic copolymerizations of geometrical isomers of 1,2-dimethoxy- and 1,2-diethoxyethylenes with vinyl isobutyl ether as a reference monomer have been carried out in methylene chloride at ?70° using boron trifluoride etherate as catalyst. The kinetics of the acid-catalyzed hydrolysis of these ethers has also been investigated in 80% aqueous dioxane, in order to compare the results with the polymerizabilities. It has been found that the cis ethers are ca. four times as reactive as their trans isomers in both reactions. On the other hand, it has been proved that a β-alkoxyl substitution reduces the hydrolysis reactivity of vinyl alkyl ethers by a factor of ca. 10^?3 while it even enchances the cationic polymerizability. These contrasting results are interpretable from the nature of the transition states which are different for the two reactions.     

Stereochemie des Übergangszustandes aliphatischer CLAISEN-Umlagerungen. Vorläufige Mitteilung

The stereochemistry of the transition state in the CLAISEN rearrangement of crotyl propenyl ethers ( 2 ) has been established. By heating trans, cis-, cis, cis- and trans, trans-crotyl propenyl ether at 142,5°, erythro and threo 2, 3-dimethylpent-4-en-1-al ( 3 and 4 ) were obtained. From the ratio 3/4 it was shown that the rearrangement of the three ethers largely involves (97–98%) a chair-like transition state.     

Jacobsen-type enantioselective hydrolysis of aryl glycidyl ethers. 31P NMR analysis of the enantiomeric composition of oxiranes

The enantioselective partial hydrolysis of a number of racemic aryl glycidyl ethers in the presence of chiral Co(salen)-catalyst was studied. The enantiomeric composition of the isolated (R)-aryl glycidyl ethers was analyzed by ³¹P NMR using optically active substituted 2-chloro-1,3,2-dioxaphospholanes. A synthesis of -adrenoblocking agents (S)-toliprolol and (S)-moprolol based on the simultaneously obtained (S)-3-aryloxypropane-1,2-diols was proposed.     

Fluorescence reagents. I. Derivatization of carboxylic acids,imides and alcohols with 1-chloromethylbenz[c,d]indol-2(1H)-one (CMBI)

The derivatization and fluorodensitometric determination of carboxylic acids (CA), imides and alcohols with 1-chloromethylbenz[c,d]indol-2(1H)-one ( 19 , CMBI) have been studied. Out of a series of fluorescent fused lactams 9-11, 13-15 and 17 , benzindolone 17 was selected and transformed via hydroxymethylbenzin-dolone 18 into CMBI 19. CMBI reacts with CA, diCA and alcohols respectively to yield strongly fluorescent benz[c,d]indol-1-ylmethyl esters 20, 21 (BIM esters) and BIM ethers 22. Phenobarbital is transformed by action of CMBI into fluorescent 1,3-bisBIM phenobarbital 25. Studies on the applicability of the derivatization reactions to the fluorodensitometric determination of CA, alcohols and imides showed that CA with more than 3 carbon atoms can be determined via BIM esters down to the low picomole range. In the case of alcohols and imides the results were not satisfying. The ir, uv, fluorescence, nmr and mass spectra of the prepared benzindole derivatives are also presented.     

Experiments on the total synthesis of Lysolipin I. Part II. Michael addition of 1,3-cyclohexanedione to quinone acetals

Base-catalyzed reaction of 1,3-cyclohexanedione ( 3 ) with the quinone monoacetals 4 and 7 leads to the polycyclic products 5 and 8 , respectively, and in the case of 4 to variable amounts of dibenzofuranone 6 . The 2-arylcyclohexanedione 9 , on the other hand, is isolated from the reaction of 3 and bisacetal 11 catalyzed by ZnCl₂ (Scheme 2). Treatment of the adduct 8 with (CH₃O)₂SO₂/K₂CO₃ results in cleavage of teh heterocyclic ring by a retro-Michael reaction affording teh liable enone 23 which was further transformed to 24 by selective hydrogenation. The 8-acetoxydibenzofuranone 22 is obtainable from 8 by acid treatment and acetylation (Scheme 4). The reactions of the silylenol ethers 27 and 35 with quinone monoacetals were very complex (Scheme 6). The desired arylcyclohexanone derivatives 28 and 36 were formed in very low yields. Under certain conditions (elevated temperature or strong Lewis acids as catalysts), single-electron transfer or addition to the ene-acetal rather than to the enone function of the quinone monoacetals became predominant. In connection with this study, the sensitive 2-methoxy-p-benzoquinone monoacetals 15 (Scheme 3) and 29 (Scheme 6) have been prepared and characterized.     

Cationic polymerization of α,β-disubstituted olefins. V. Reactivity of propenyl alkyl ethers in cationic polymerization

To elucidate the effect of the introduction of a methyl group in the β-position of a vinyl monomer, propenyl alkyl ethers were copolymerized with vinyl ethers having the same alkoxy group. Propenyl alkyl ethers with an unbranched alkoxy group (ethyl or n-butyl propenyl ether) were more reactive than the corresponding vinyl ethers. This behavior is quite different from that of β-methylstyrene derivatives. However, propenyl alkyl ethers with branched alkoxy groups at the α carbon atom (isopropyl or tert-butyl propenyl ether) were less reactive than the corresponding vinyl ethers. Also, cis- isomers were more reactive than the trans isomers, regardless of the kind of alkoxy group and the polarity of the solvent.     

Glycosylidene Carbenes. Part 24 Reactivity modulation by protecting groups of the addition of glycosylidene carbenes to electron-rich alkenes

The reactivity of glycosylidene carbenes derived from pivaloylated vs. benzylated diazirines 1 and 2 towards enol ethers have been examined. The pivaloylated 1 led to higher yields of spirocyclopropanes than the benzylated 2. Among the enol ethers tested, dihydrofuran 6 proved most reactive, yielding 71–72% of the spiro-linked tetrahydrofuran 7 , while the benzylated diazirine 2 afforded only 33% of the analogue 8 (Scheme 1 ). Other enol ethers proved much less reactive. The addition of 1 and 2 to the dihydropyran 10 and the 2, 3-dihydro-5-methyl-furan 15 gave low yields of single cyclopropanes (→ 12 , 14 , and 16 ), and the glycals 17 and 18 , and (E)-1-methoxy-oct-1-ene ( 23 ) did not react. The main products of these reactions were the azines (Z, Z)- 11 and (Z, Z)/( E, E)- 13. Similarly, 1 and 2 reacted poorly with (Z)-1-methoxyoct-1-ene ( 24 ), leading to cyclopropanes 25 / 26 / 27 and 28 / 29 / 30 / 31 (Scheme 2). Main products were again the azines (Z, Z)- 11 and (Z, Z)/(E, E)- 13 . The structure of 70 and 25 was established by X-ray analysis (Figs. 1 and 2). The mechanism of addition of glycosylidene carbenes to enol ethers is discussed, AMI Calculations indicate that the LUMO_carbene/HOMO_alkoxyalkene interaction is dominant at the beginning of the reaction, while the transition states are characterized by a dominant interaction of the doubly occupied, sp²-hybridized orbital of the carbene with the LUMO of the enol ether. The relative reactivity of the carbenes towards either the enol ethers or the diazirines determine type and yields of the products.     

Stereochemistry in cationic polymerization of alkenyl ethers. V. Stereochemistry of acetal additions as model reactions for the polymerization of alkenyl ethers

Acetal additions to β-substituted vinyl ethers having a variety of substituents (alkenyl ethers) were stereochemically investigated as model reactions for their cationic polymerization. The reactions catalyzed by BF₃O(C₂H₅)₂ in CH₂Cl₂ at O°C gave 1:1 adducts, the steric structure of which was determined by means of ¹³C-NMR spectroscopy. trans-Alkenyl ethers always gave adducts with a single structure stereospecifically, indicating that the intermediate carbocation attacks a trans-alkenyl ether from a definite direction independent of the bulkiness of substituents. On the other hand, cis-alkenyl ethers formed adducts with two steric structures, and the direction of cation addition was found to depend on the bulkiness of the alkoxy group involved. The above trends were in agreement with the results for poly(alkenyl ether)s and allowed detailed discussion of the stereochemistry of the propagation processes in alkenyl ether polymerizations.