Structure of Styrene and Acrylate Block Copolymers

Abstract

Using UV light as the energy source and polystyrene- (PS-) or polymethyl methacrylate- (PMMA-) macroinitiators with active aromatic or aliphatic thiyl end groups, PS-PMMA and PMMA-PEA (poly-ethyl acrylate) block copolymers were synthesized. The molecular weights of both block copolymers increased with increasing reaction time. The reactivity of macroinitiators depended on the type of thiyl groups and monomer and not on the length of the polymer chain. The most reactive were macroinitiators containing resonance stabilized non-substituted or substituted aromatic end groups. The decomposition of the macroinitiators took place over the formation of the thiyl radical and macroradical. The bond length, the bond dissociation energy, and the bond order of macroradical end groups were calculated. The most reactive monomer was ethyl acrylate; the less reactive was styrene. The structure, the molecular weight, and the T _g of the styrene-acrylate block copolymers were determined. The PMMA/PEA block copolymer had two of block's T _g s, the first at 105°C, the second at ?24°C, and a third at 16°C which probably represents contacting segments.     

Phosphorylated Bromonitroethene in the Reactions with NH- and CH- Acids

Abstract

The interaction between O,O-di(2-dichloroethyl)-2- bromo-2-nitroethenephosphonate and some NH- and CH-acids is discussed.

The highly reactive halonitroethenes attract the attention of scientists so as they are active synthons in the synthesis of various classes of organic compounds. Phosphorylated halonitroethenes can represent particular interest, because of phosphoryl group introduction “a priori” makes the reactivity of such compounds to be higher and allows to synthesize a big number of biologically active compounds. The very first study of interaction between O,O-di(2-chloroethyl)-2-nitroethenephosphonate (1)¹ with some representatives of NH-and CH-acids such as anyline, p-toluydine, dimedone, and malonic ester was conducted by our research group.     

Synthesis,Characterization and Theoretical Study of the Chemical Reactivity of New Cyclic Sulfamides Linked to Tetrathiafulvalene

Abstract

The synthesis of the title compounds has been carried out by condensation via a Wittig-type reaction of a pyridinium hexafluorophosphate with a phosphonate ester to give the desired (4-nitrophenyl)tetrathiafulvalene the nitro group of which was reduced to an amino group. Reaction of the amine with chlorosulfonyl isocyanate and subsequently with tert-butyl alcohol gave the corresponding open-chain sulfamide. Cyclization under basic conditions and de-protection led to 2-[4-(4′,5′-dipropyltetrathiafulvalen-4-yl)]phenyl-1,2,6-thiadiazinane 1,1-dioxide. Finally, N-alkylated and N-acylated cyclic sulfamides linked to tetrathiafulvalene were obtained. Their electron donor ability was measured by cyclic voltammetry. A detailed DFT study based on B3LYP/6–31G (d,p) of electronic properties is also presented. The calculated molecular electrostatic potential shows that, the negative charge covers the nitro and sulfamide function, while positive charge is located at the hydrogen atoms of the amine and sulfamide rings. The calculated HOMO and LUMO energy reveals that charge transfer occurs within the molecule. The chemical reactivity parameters reveal that tetrathiafulvalene 1 is highly reactive, which facilitates the desired formation of the cyclic sulfamide. The first hyperpolarizability β_tot shows that compounds 1 and 5 are good candidates as a NLO material.     

Arylsulfonylation of N-isobutylaniline and its derivatives: experimental study and quantum-chemical calculations

The kinetics of the reactions of benzene-substituted N-isobutylanilines 1a—h with 3-nitrobenzenesulfonyl chloride in propan-2-ol was studied at 298 K. To analyze the reactivities of compounds 1a—h in the arylsulfonylation reactions and substantiate the possible mechanism of these reactions, the geometric, electronic, and energy characteristics of the reagents and a series of model compounds were calculated by the semiempirical quantum-chemical AM1 and PM3 methods. The rate of arylsulfonylation of N-isobutylaniline and its derivatives increases directly proportional to the contributions of the s and p _z orbitals of the N atoms to HOMO of amine and of the S atoms to LUMO of sulfonyl chloride. The coefficients of these AOs can be considered as the reactivity indices of the reagents used for arylsulfonylation of substituted N-isobutylanilines with aromatic sulfonyl chlorides. It was proposed that the reaction under study is orbital-controlled.     

Reactivity of Dicoordinated Stannylones (Sn0) versus Stannylenes (SnII): An Investigation Using DFT‐Based Reactivity Indices

The reactivity of dicoordinated Sn⁰ compounds, stannylones, is probed using density functional theory (DFT)‐based reactivity indices and compared with the reactivity of dicoordinated Sn^II compounds, stannylenes. For the former compounds, the influence of different types of electron‐donating ligands, such as cyclic and acyclic carbenes, stannylenes and phosphines, on the reactivity of the central Sn atom is analyzed in detail. Sn⁰ compounds are found to be relatively soft systems with a high nucleophilicity, and the plots of the Fukui function f^? for an electrophilic attack consistently predict the highest reactivity on the Sn atom. Next, complexes of dicoordinated Sn compounds with different Lewis acids of variable hardness are computed. In a first part, the double‐base character of stannylones is demonstrated in interactions with the hardest Lewis acid H⁺. Both the first and second proton affinities (PAs) are high and are well correlated with the atomic charge on the Sn atom, probing its local hardness. These observations are also in line with electrostatic potential plots that demonstrate that the tin atom in Sn⁰ compounds bears a higher negative charge in comparison to Sn^II compounds. Stannylones and stannylenes can be distinguished from each other by the partial charges at Sn and by various reactivity indices. It also becomes clear that there is a smooth transition between the two classes of compounds. We furthermore demonstrate both from DFT‐based reactivity indices and from energy decomposition analysis, combined with natural orbitals for chemical valence (EDA‐NOCV), that the monocomplexed stannylones are still nucleophilic and as reactive towards a second Lewis acid as towards the first one. The dominating interaction is a strong σ‐type interaction from the Sn atom towards the Lewis acid. The interaction energy is higher for complexes with the cation Ag⁺ than with the non‐charged electrophiles BH₃, BF₃, and AlCl₃.     

Structure-Toxicity Relationships for Aliphatic Compounds Encompassing a Variety of Mechanisms of Toxic Action to Vibrio fischeri

Abstract

QSARs based upon the logarithm of the octanol-water partition coefficient, logP, and energy of the lowest unoccupied molecular orbital, E_LUMO were developed to model the toxicity of aliphatic compounds to the marine bacterium Vibrio fischeri. Statistically robust, hydrophobic-dependent QSARs were found for chloroalcohols and haloacetonitriles. Modelling of the toxicity of the haloesters and the diones required the use of terms to describe both hydrophobicity and electrophilicity. The differences in intercepts, slopes, and fit of these models suggest different electrophilic mechanisms occur between classes, as well as within the diones and haloesters. In order to model globally the toxicity of aliphatic compounds to V. fischeri, all the data determined in this study were combined with those determined previously for alkanones, alkanals, and alkenals. A highly predictive two-parameter QSAR [pT₁₅ = 0.760(log P) ?0.625(E _LUMO) ?0.466; n = 63, s = 0.462, r ² = 0.846, F = 171, Pr > F = 0.0001] was developed for the combined data that models across classes and is independent of mechanisms of action. The toxicity of these compounds to V. fischeri compares well to the toxicity (50% population growth inhibition) to the ciliate Tetrahymena pyriformis (r ² = 0.850).     

Utilization of cyanoacetohydrazide and 2-(1,3-dioxoisoindolin-2-yl) acetyl chloride in the synthesis of some novel anti-proliferative heterocyclic compounds

Abstract

Owing to its high reactivity and commercial availability, 2-cyanoacetohydrazide can be utilized as a versatile and appropriate intermediate for synthesis of a broad variety of heterocyclic compounds. Thus, 2-cyanoacetohydrazide and 2-(1,3-dioxoisoindolin-2-yl) acetyl chloride were used as starting materials for construction of new heterocyclic compounds bearing 1,3-dioxoisoindoline moiety. The newly synthesized compounds were recognized by elemental analyses and spectral data (IR, ¹H-NMR, and ¹³C-NMR spectra). The synthesized compounds were screened for their anti-proliferative activity against two human epithelial cell lines; breast (MCF-7) and liver (HepG2) as well as to normal fibroblasts (WI-38). The data showed distinctly that compounds 1 and 12 presented promising in-vitro anti-proliferative activity against two cell lines (MCF-7 and HepG2) without harming normal fibroblasts.     

Chemistry of novolac resins. X. Polymerization studies of HMTA and strategically synthesized model compounds

The reactions between hexamethylenetetramine (HMTA) and compounds which model novolac resins have been studied by ¹³C‐ and ¹⁵N‐NMR techniques. The dimer and tetramer compounds vary in molecular size and structure and react with HMTA to yield benzylamines and benzoxazine as the major initial‐formed intermediates and convert to methylene linked compounds at increased temperatures. The reaction of the compounds with only ortho reactive sites paralleled the 2,4‐xylenol–HMTA case reported by us previously; however, increasing molecular weight favored the formation of benzylamines and not benzoxazines. Those compounds with only para reactive sites paralleled the 2,6‐xylenol–HMTA case. The reactivity of the systems containing both ortho and para reactive sites depends on the ratio of ortho/para sites and various aspects such as the chemical structure and molecular weight of the compound, the HMTA level, and the melting point and pH of the system. These results parallel those obtained from novolac/HMTA systems. The xylenol/HMTA reactions formed similar products but showed quite different relative reaction rates by varying the HMTA ratio and structures of the materials. The importance of careful selection of model systems is also discussed. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1347–1355, 1999     

Dioxin-Type Activity for Polyhalogenated Arylic Derivatives. A QSAR Model Based on MTD-Method

Abstract

QSARs by the Minimal Steric/Topologic Difference (MTD)-method were performed for general toxicity, hepatic cytosol receptor binding and aryl hydrocarbon hydroxylase induction on polychlorinated and polybrominated derivatives of dibenzo-p-dioxin, dibenzofuran and biphenyl. Low energy conformations selected by molecular mechanics calculations and superpositions of the considered structures for the construction of the hypermolecule were performed using the COSMIC molecular modelling package. The multiconformational-MTD-method was used. Correlation coefficients of r = 0.8 to 0.9 were obtained as well as good cross-validation results, for series of up to 70 compounds. Conformational analysis of flexible molecules suggests their accommodation in the receptor site also in non planar conformations corresponding to the first stable one (minimum energy costs) above the global minimum. A common optimised receptor site can be attributed for all series of compounds, with a rather high symmetry, which suggests that these compounds produce gene activation by dimerization of their receptor protein. The high toxicity of dioxin-type compounds could be explained by their high stability that produce long lasting, abnormally high levels of some detoxification enzymes—without toxic effects at their low and normal levels.     

α-Glucosylation Reactions with 2,3,4,6-Tetra-O-Benzyl-β-D-Glucopyranosyl Fluoride and Triflic Anhydride as Promoter

ABSTRACT

Triflic anhydride is a suitable promoter for the glucosylation of glycosyl aceptors of medium or low reactivity using 2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl fluoride as donor. In the glucosylation of reactive hydroxyl groups competing triflate formation was observed. The use of molecular sieves as acid scavenger allows the formation of triflates of reactive alcohols under non-basic conditions.     

METALLAPHOSPHENES AND DIPHOSPHENES

Abstract

Transient metallaphosphenes (rbnd2;M[dbnd]P[sbnd]) have been obtained by exchange reactions between disilylphosphines and organometaldihalides (M = Ge, Sn), or by thermolysis of 2-metallaphosphetanes (M = Si, Ge). They are characterized by trapping reactions with strained heterocycles. The first stable germaphosphene 12 has been synthesized by dehydrohalogenation from the parent halogermylphosphine and isolated in form of orange crystals. It is very reactive toward compounds with active hydrogen.

Transient diphosphenes ([sbnd]P[dbnd]P[sbnd]) have been prepared by the same type of exchange reactions between disilylphosphines and dichlorophosphines and characterized by trapping reactions on dienes. The second stable diphosphene 18 has been obtained by addition of t-BuLi on trisyldichlorophosphine. Its structure has been determined by X-ray diffraction and some aspects of its reactivity are described. The reaction of bisyltrichlorogermylphosphine with DBU affords the new stable and potentially reactive diphosphene 30.     

Theoretical investigation of different reactivities of Fe(IV)O and Ru(IV)O complexes with the same ligand topology

The structures and mechanisms for hydrogen abstraction from isopropylbenzene for four high-valence complexes, cis-β-[Fe^IV(O)(BQCN)]²⁺ (Fe-2b and Fe-2b-2) and cis-β-[Ru^IV(O)(BQCN)]²⁺ (Ru-2b and Ru-2b-2) (BQCN = N,N′-dimethyl-N,N′-bis(8-quinolyl)-cyclohexanediamine), were investigated using density functional theory. Of the two iron complexes, Fe-2b-2 has more exposed FeO units than Fe-2b, with iron being further out of the equatorial plane because of the steric interaction of the same ligand topologies with the iron-oxo group trans to a quinolyl or amine nitrogen. The contribution of BQCN to Fe-2b is higher than the contribution to Fe-2b-2 as shown by the density-of-states spectra. The iron isomers can abstract hydrogen from isopropylbenzene via two-state reactivity patterns, whereas the ruthenium isomers react with isopropylbenzene via a single-state mechanism. In the gas phase, the relative reactivity exhibits the trend Fe-2b > Fe-2b-2, whereas with the addition of the ZPE correction and the SMD model, the relative reactivity follows Fe-2b-2 > Fe-2b. For the ruthenium complexes, the relative reactivity follows the trend Ru-2b-2 > Ru-2b in both the gas phase and solvent. Thus, the same ligand topologies with the metal-oxo group trans to a different nitrogen affect the reactivities of the iron and ruthenium complexes.     

Cationic copolymerization of anethole: Reactivity of geometric isomers of α,β-disubstituted ethylenes

Cationic copolymerizations of anethole were carried out under various conditions in order to confirm the relative reactivities of its geometric isomers. trans-Anethole was more reactive than cis-anethole in copolymerizations with p-methoxystyrene or styrene, but less reactive in the mutual copolymerization of cis- and trans-anethole; i.e., the trans isomer was more reactive to a growing chain end with little steric hindrance. Thus the intrinsic reactivity of an olefinic double bond to carbonium ion is greater for the trans isomer than for the cis isomer. This idea is supported by ¹³C NMR spectra, since the signal of the olefinic β-carbon of the trans isomer is at higher field than that of the cis isomer. The behavior of anethole was compared with the results observed in vinyl ethers, where the cis isomer was always more reactive irrrspective of the structure of the growing chain end. In addition, the dependence of monomer reactivity ratios on polymerization conditions is discussed.     

Reactivities of cis- and trans-3-substituted acrylic acids on copolymerization with acrylamide

Several pairs of cis- and trans-3-substituted acrylic acids (3SAA) were copolymerized with acrylamide in order to determine the major factors affecting the relative reactivities of geometrical isomers of 1,2-disubstituted ethylenes (1,2-DE). The results were that the relative reactivity of cis isomer is larger than that of trans isomer when one substituent is electron-withdrawing and the other is electron-donating. The trans isomer is more reactive than the cis isomer when both substituents are electron-withdrawing. A new method of reactivity comparison of cis- and trans-1,2-DE is proposed in regard to the inductive substituent constant.     

RECENT IMPROVEMENTS TOWARDS THE SYNTHESIS OF THE C-GLUCURONOSYL CANCER CHEMOPREVENTIVE (β-d-GLUCOPYRANOSYLURONATE)-4-RETINAMIDOPHENYLMETHANE

Evidence suggests that the glucuronide conjugates of retinoids may be active metabolites of the parent compounds with potential utility as drugs.¹ We have recently shown that the O-glucuronide metabolite 1 of the synthetic retinoid N-4-hydroxyphenylretinamide (2) shows reduced toxicity and a significant chemopreventive advantage relative to the parent retinoid in a carcinogen-induced rat mammary cancer model.² In efforts to determine whether these conjugates function as intact molecules or must be hydrolyzed back to 2, we designed and synthesized a series of C-glycosyl and C-glucuronosyl analogues of 1 ³. Our syntheses of these compounds are lengthy (10-12 steps) and lead to the desired products in less than 4% overall yields. Limitations on the availability of these compounds led us to evaluate them using a modified protocol for the carcinogen-induced rat mammary tumor model. While many of our analogues showed cancer chemopreventive activity in this assay, C-glucuronosyl analogue 3 has proven to be the most effective analogue of 2 we have yet evaluated in this model.⁴ Unfortunately, compound 3 was prepared in the poorest overall yield among these analogues. However, its potent activity and low toxicity make it an important candidate for expanded biological studies. Because additional studies of this important new compound will benefit from improvements in its synthesis, we briefly describe below recent dramatic improvements we have made in the preparation of 3.