Cinétiques de télomérisation, 4. Nouvelle méthode de détermination des constantes de transfert en catalyse radicalaire

For the determination of transfer constants C_T to the telogen in telomerization reactions started with free radicals we used three methods. The first one is the method of Mayo, the second one is based on the variation of the conversion degree of telogen to monomer and the last method requires the knowledge of the cumulated number-average degree of polymerization DP _n and monomer conversion α_M of the samples during the reaction. Verifications of the proposed laws are made for methacrylic acid telomerization with CCl₃Br and methyl methacrylate telomerization with benzenethiol as a telogen and 2,2′-azoisobutyronitrile as the initiator at 70°C. The transfer constant to CCl₃Br is ca. 0,03 and that to C₆H₅SH ca. 1,5.     

Synthèse de cotélomères photoréticulables, 6. Utilisation de cotélomères biséquencés

Photocrosslinkable block cotelomers were synthesized in three steps. In the first step a monomer M₁ was telomerized with carbon tetrachloride or chloroform, in the second step a monomer M₂ with the resulting macrotelogen, and in the third step the hydroxyl groups were esterified by cinnamic acid or acrylic acid. These reactions were carried out with ethyl acrylate (M₁)/CCl₄ by redox catalysis and subsequently with vinyl acetate (M₂) by free radical initiation, or with vinyl acetate (M₁)/CHCl₃ by free radical initiation and subsequently with isoprene (M₂) by redox catalysis, or with 2-hydroxyethyl acrylate (M₁)/CCl₄ by redox catalysis, and subsequently with isoprene (M₂) by redox catalysis.     

Cinétique de télomérisation, 3. Détermination des constantes de tranfert en catalyse rédox

Three methods were used for the determination of transfer constants to the metallic complex in the telomerization reaction with redox catalysis. The first one consists in the determination of DP _n as a function of the mole ratio of telogen to monomer at the beginning of the reaction. The second one is based on the variation of the conversion degree of telogen to monomer. The last one requires the knowledge of the cumulated DP _n and the conversion degree of monomer samples during the reaction. The proposed laws were checked following the methyl acrylate telomerisation with CCl₄ as a telogen and CuCl₂ as a catalyst at 120°C. The transfer constant to CuCl₂ was found to be about 600 according to the three methods.     

Synthèse et copolymérisation avec l'acrylamide de macromonomères d'acrylate de dodécyle

Graft copolymers of well-defined structure and composition were prepared by radical copolymerization of acrylamide and poly(dodecyl acrylate) macromonomers. The macromonomers were prepared by telomerization of dodecyl acrylate in the presence of 2-mercaptoethanol as a transfer agent, followed by reaction with acryloyl chloride. Poly(dodecyl acrylate) macromonomers with M _n = 1100, 1100, 2200 and 4600 were synthesized. The kinetics of the radical telomerization of dodecyl acrylate with 2-mercaptoethanol and AIBN was studied at 66°C in THF. Under these conditions we obtained the transfer constant C_T = 0,9. The graft copolymerization of acrylamide with the poly(dodecyl acrylate) macromonomer was carried out in the presence of the transfer agent C₆F₁₃C₂H₄SH. If C₀ = [AIBN]/[Acrylamide] = 0,01 and R₀ = [C₆F₁₃C₂H₄SH]/[Acrylamide] = 0,01, for acrylamide a DP _n = 160 was obtained in all cases, for the macromonomer of M _n = 1100 a DP _n = 2,5, and for the macromonomer of M _n > 1100 a DP_n = 1.     

Synthèse et transformations chimiques des télomères de l'undécène-10 oate de méthyle, 1

Redox of radical telomerizations of methyl 10-undecenoate (1) with different telogens such as CCl₄, CCl₃Br, CCl₃CF₃, HPO (OEt)P₂ or different adducts of CCI₄, on vinylidene chloride and chlorotrifluoroethylene, were studied. Chemical transformation of the end of the chains led to the corresponding difunctional compounds. Starting with these last compounds, polycondensation reactions were carried out.     

Cinétiques de télomérisation, 6. Détermination des degrés de polymérisation a partir de la répartition moléculaire

It is shown that the kinetic laws established for polymerization reactions can be applied for telomerization reactions provided the number-average degrees of polymerization DP _n are greater than ten. For DP _n > 10 it is necessary to calculate the molecular distributions. Values of DP _n obtained with the method of Mayo and the molecular distribution method are compared and an experimental application is given by the radical-initiated telomerization of glycidyl methacrylate (2,3-epoxypropyl methacrylate) with bromotrichloromethane.     

Télomères monofonctionnels du chlorure de vinyle, 3. Cinétique par catalyse rédox

A kinetic study of the redox telomerization of vinyl chloride with carbon tetrachloride was carried out. Transfer constants of PVC to the metallic ion (C_Feⁿ), initiation rate (k_i), and functionnality of the resulting telomers were measured. Instantaneous and cumulated polymerization degrees, (DP_n )_i and (DP_n )_cum were determined with the help of a theoretical study. These constants provide a rigorous control of the telomerization of vinyl chloride with RCCl₃, (R containing an alcohol or ester group).     

Cinétiques de télomérisation, 1. Determination des lois applicables à la synthèse des télomères à DPn moyens en télomérisation radicalaire

The kinetics of free radical telomerization was studied. The theoretical relations that can be applied in reactions of this type, were evaluated. When transfer predominates, the equations giving the variations of monomer, telogen and initiator as a function of time were established. Moreover, instantaneous and cumulated number and weight average degrees of polymerization were calculated. The resulting relations were checked on the example of the telomerization of 2,3-epoxypropyl methacrylate with bromotrichloromethane in the presence of two initiators and two different temperatures. Comparison of the experimental results with the theoretical ones revealed the scope of application of the general formulae giving the average degrees of polymerization.     

Radical telomerization of vinyl acetate with chloroform. Application to the synthesis of poly(vinyl acetate)‐block‐polystyrene copolymers by consecutive telomerization and atom transfer radical polymerization

This paper demonstrates that radical telomerization and atom transfer radical polymerization (ATRP) can be combined in a two‐step procedure to prepare poly‐(vinyl acetate)‐block‐polystyrene (PVOAc‐b‐PSt) diblock copolymers. The first step consists in telomerizing VOAc with chloroform, leading to trichloromethyl‐terminated VOAc telomers CCl₃(VOAc)_nH. A detailed ¹H NMR analysis shows that nearly pure telomer structures are obtained over a broad range of DP_n values (up to at least 60 units). When ATRP of styrene is initiated with a model telomer adduct (CCl₃CH₂CH₂OAc), molecular weights increase linearly with monomer conversion and match theoretical values. Moreover, polydispersities are consistently low (1.22 < M_w/M_n < 1.38) throughout polymerization. Similarly, VOAc telomers (DP_n = 9 and 62) are good ATRP macroinitiators. The high purity of the resulting diblock copolymers is confirmed by GPC using RI/UV dual detection.     

Télomérisation en milieu aqueux, 1. Télomérisation de l'acide acrylique avec l'acide thioglycolique

The telomerization of acrylic acid with thioglycolic acid (mercaptoacetic acid) in aqueous medium, with various initiators (H₂O₂,Na₂S₂O₈,K₈ thermal initiation and 2,2′-azobis (2-amidiniopropane) dihydrochloride) has been achieved. Thus, we were able to point out the limitation of the chain length due to the transfer agent, which is characteristic of a telomerization reaction. Mono-, di-and tri-adducts were isolated and characterized after esterification of the reaction medium with ethanol, then hydrolized. These various adducts were used as standards for size-exclusion chromatography, and the influence of the reaction parameters (initiator, temperature, quality of solvent, amount of telogen was investigated). We also determined the transfer constant of thioglycolic acid (C_T = 0,47). It is worth to note that knowing this value, it is possible to control precisely the number -average degree of polymerization of this type of reaction. This allowed us to prepare telomers with a 50% final weight concentration in the dry extract, as it was recommended for their use in paper industry.     

Etude de la télomérisation de l'acide acrylique par les mercaptans, 1 Télomérisation de l'acide acrylique par l'acide thioglycolique; Influence de la nature du solvant sur la valeur de la constante de transfert et de kp/√kte

The telomerization of acrylic acid (AA) with thioglycolic acid (TGA) initiated with 2,2′‐azoisobutyronitrile (AIBN) was first investigated in organic medium (THF, 65°C). The kinetic study of this telomerization led to the determination of the TGA transfer constant (C_T = 3.2) and to the ratio k_p/√k_te equal to 0.48 L^1/2·mol^–1/2·s^–1/2. Then, the same study was performed both in aqueous medium and in water/THF mixture in order to investigate the solvent effect on the transfer constant. From these works it is emphasised that the nature of the solvent plays an important role on the kinetics parameters. First, this research underlined an increase of the k_p/√k_te value by raising the water proportion in water/THF mixtures. Then, the kinetic study showed the highest value for the k_p/√k_te constant, equal to 2.48 L^1/2·mol^–1/2·s^–1/2 when the telomerization proceeded in water. Consequently, the value of C_T, which is directly influenced by the k_p/√k_te constant, presented a decrease from C_T = 3.2 in THF to a value equal to 0.5 in water. By this way, the « ideal » case of telomerization (C_T = 1) was reached for a mixture of solvents; 80% water/20% THF (v/v).     

Synthèse de macromères à base de chlorures de vinyle et de vinylidène au moyen de télomères

New macromers 4, 8, and 10, containing ester, alcohol, or acid functions, were prepared starting with vinyl chloride (CV) or vinylidene dichloride (CV₂). The telomer 1, resulting from CV₂ and CCI₄ was telomerized with allyl acetate and the product was transformed into the acrylate 4 by hydrolysis of the reaction product and subsequent esterification. Macromers 8 and 10 were prepared from CV by radical telomerization with thioglycolic acid (7) and 2-mercaptoethanol (9), respectively. Reactive double bonds were introduced into these macromers by reaction with acrylic acid, Vinyl chloroformate, methacryloyl chloride, or 2,3 -epoxypropyle methacrylate, leading to new macromers 12, 13, 14, and 15, respectively.     

Synthèse de monoalcools et de monoacides chlorofluorés par télomérisation avec des telogènes chlorofluorés

Telomerizations of chlorofluorinated telogens CF₃CCl₃ and \documentclass{article}\pagestyle{empty}\begin{document}$${\rm Cl\rlap{--} (CFCl \hbox{---} CF}_{\rm 2} {\rm \rlap{--} )}_{\rm n} {\rm CCl}_{\rm 3}$$\end{document} (1 ≤ n ≤ 4) with acrylic, allylic, and vinylic monomers were studied. With allyl alcohol and 2-hydroxyethyl acrylate the corresponding fluorinated adducts 1 and 2 were obtained directly. Vinyl and allyl acetates led to the adducts 4a , b and 5a , b , respectively, which could be transformed into the corresponding acetals and alcohols. Telomerizations of methyl acrylate and methacrylate led to the fluorinated adducts 12a and b in the presence of copper chloride as catalyst or also with iron trichloride in the case of methyl methacrylate. By intramolecular elimination the methacrylate adducts were transformed into the lactons 13 and 14 and the acrylate adducts by reduction into the alcohols 1 and 2 . The same reduction of the methacrylate adduct led to the 2,4,4-trichloro-5,5,5-trifluoro-2-methyl-1-pentanol ( 15 ). Independent on the applied catalyst the telomerization of vinylacetic acid led to the monoaddition product, whereas in the case of methacrylic or acrylic acid the formation of monoadducts or higher addition products was found to depend on the catalyst.     

Etude de la diaddition de l'acétate d'allyle sur les télogènes chlorofluorés possédant deux groupements CCl3 en extrémité de chaîne

The redox catalyzed addition of compounds such as Cl₃C? CF₂? CCl₃ and Cl₃C? CF₂? CCl₂? CH₂? CHCl? CH₂? OCOCH₃ to allyl acetate was studied with the purpose of obtaining telechelic products. RuCl₂[P(C₆H₅)₃]₃ was used as catalyst, and its action was compared to that of cooper- or iron-based catalysts. The products were isolated and their structures studied by means of ¹³C, ¹⁹F and ¹H NMR spectroscopy. The reaction mechanism was studied to improve the yield of the diaddition product for its utilisation as monomer in polycondensation reactions. It was found that the low reactivity for a second addition is not due to the presence of a chlorine atom in β-position of the acetate function. When allyl acetate was replaced by allyl bromide or chloride in the first addition, the second addition to allyl acetate occurred normally.     

Synthèse de composées photoréticulables, 7. Télomères des acides acrylique et méthacrylique gréffés par méthacrylate d'époxy-2,3 propyle

Telomers were prepared from acrylic or methacrylic acid and CCl₃Br, C₁₂H₂₅SH, C₁₈H₃₇SH or C₈F₁₇C₂H₄SH by initiation with 2,2'-azoisobutyronitrile. The transfer constant of CCl₃Br and the thiols, which are about 0,03 and 0,5, respectively, were determined. These telomers were used as supports of photopolymerizable functions, which were introduced by grafting of 2,3-epoxypropyl methacrylate, catalysed with dodecyldimethylamine. The reactions were followed by ¹H NMR, elemental analyses, tonometrie, and especially by GPC and titration of the acid functions. The grafting telomers, holding many acrylic functions which react upon UV and electron irradiation, give photoreticulated varnish coatings with very interesting properties.     

Carbon tetrachloride induced kidney and lung tissue damages and antioxidant activities of the aqueous rhizome extract of <Emphasis Type="Italic">Podophyllum hexandrum</Emphasis>

Background  

The present study was conducted to evaluate the in vitro and in vivo antioxidant properties of aqueous extract of Podophyllum hexandrum. The antioxidant potential of the plant extract under in vitro situations was evaluated by using two separate methods, inhibition of superoxide radical and hydrogen peroxide radical. Carbon tetrachloride (CCl₄) is a well known toxicant and exposure to this chemical is known to induce oxidative stress and causes tissue damage by the formation of free radicals.     

The role of glutathione in chloroform-induced hepatotoxicity.

Chloroform (CHCl₃) administered to phenobarbital-pretreated rats decreased liver glutathione (GSH) and caused massive liver necrosis. Only those doses of CHCl₃ that decreased GSH in the liver caused centrilobular liver necrosis. Other halogenated alkanes studied, including CCl₄ and CCl₃Br, did not deplete liver GSH in phenobarbital-pretreated rats. In rats pretreated with 3-methylcholanthrene, isopropyl alcohol, or acetone, which also increase drug metabolism, CHCl₃ did not markedly decrease GSH in the liver. The GSH depletion was not due to oxidation of GSH or to inhibition of GSH reductase because CHCl₃ administration did not increase the amount of oxidized GSH in liver, whole blood, or kidney. Since only liver GSH was depleted in these experiments, it appeared that depletion was related to CHCl₃ metabolism. Since CCl₄ and CCl₃Br are postulated to form the trichloromethyl-free radical (CCl₃·), and since these compounds do not deplete liver GSH in phenobarbital-pretreated rats, the GSH depletion by CHCl₃ may be due to formation of chemically reactive metabolites other than the trichloromethyl free radical.     

Chlorella vulgaris extract ameliorates carbon tetrachloride-induced acute hepatic injury in mice

The possible protective effects of Chlorella vulgaris extract (CVE) on carbon tetrachloride (CCl₄)-induced acute hepatic injury in mice and the mechanism underlying these effects was investigated. CCl₄ administration caused a marked increase in the levels of serum aminotransferases, lipid peroxidation and cytochrome P450-2E1 (CYP450) expression. Also, decreased glutathione (GSH) content and activities of cellular antioxidant defense enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and glutathione-S-transferase (GST) were found after CCl₄ exposure. All of these phenotypes were markedly reversed by preadministration of the mice with CVE. In addition, CVE exhibited antioxidant effects on FeCl₂–ascorbate induced lipid peroxidation in mouse liver homogenates, and on superoxide radical scavenging activity. Taken together, these results suggest that CVE produced a protective action on CCl₄-induced acute hepatic injury in mice, presumably through blocking CYP-mediated CCl₄ bioactivation, inducing the GSH levels, antioxidant enzyme activities and free radical scavenging effect. Therefore, CVE may be an effective hepatoprotective agent and viable candidate for treating hepatic disorders and other oxidative stress-related diseases.     

Antagonism by chloramphenicol of carbon tetrachloride hepatotoxicity: Examination of microsomal cytochrome P-450 and lipid peroxidation

Administration of chloramphenicol early in CCl₄ intoxication prevents lipid peroxidation of endoplasmic reticulum membranes. Conversely, a sulfamoyl analog, Tevenel, was ineffective in preventing the lipoperoxidative process. Likewise, in an in vitro microsomal system chloramphenicol inhibited a lipid peroxidation process and Tevenel did not. However, both compounds bind to cytochrome P-450. Chloramphenicol did not maintain cytochrome P-450 levels after CCl₄ administration nor did it depress cytochrome P-450 levels in untreated animals. The data obtained indicate that chloramphenicol may prevent lipid peroxidation either by inhibiting CCl₄ metabolism or by acting as a free radical sequestering agent.     

Recherche de télomères à activité pharmacologique potentielle, 2. Télomères de l'acide acrylique et greffage de composés hydroxylés

Several telomers of acrylic acid with carbone tetrachloride were prepared. Their average degree of polymerization, which was between 10 and 50, was determined by several analytical methods (elemental analysis, viscosimetry, and GPC). From the kinetic equations of telomerization a relation between DP _n of these telomers and the experimental conditions is established. Fixation of hydroxylic compounds through direct esterification was studied and it was found that the prepared telomers can be used as hydrosoluble carriers for drugs containing primary alcohol or phenol functions.