The esterolytic activity of poly(1-methyl-4- and -5-vinylimidazole) in water.

The water solubility of poly(1-Me-5-VIm) has made it possible to achieve phenomenal rate enhancements and to gain even greater insight into the mechanism of catalysis by polymeric imidazoles. The poly(1-Me-5-VIm)-catalyzed hydrolysis of S12- exhibited saturation in excess catalyst nad in excess substrate. Inhibition of the poly(1-Me-5-Vim) catalyzed hydrolysis of Sn- type substrates by analog inhibitors was also observed. The saturation apparently did not follow a simple Michaelis-Menten mechanism; however, the results could be rationalized by analogy to certain enzymatic systems. Multisite enzymes have long been known to display kinetic patterns different from that exhibited by enzymes with only one active site, i.e. such phenomena as sigmoidal rate vs [S] plots. These phenomena may arise entirely as a result of the multisite nature of the enzyme. Consequently, a synthetic macromolecular catalyst with multiple sites might also be expected to display such characteristics. The poly(1-Me-5-VIm)-catalyzed hydrolysis of S12- is apparently the first synthetic system in which such phenomena have been observed. The intermediacy of an apolar polymer substrate complex for the poly(1-Me-5-VIm)-catalyzed hydrolysis of S12- in water was given support by studies of the effect of temperature on the rate of hydrolysis. Activation parameters were determined for catalysis by 1,5-DMIm and by poly(1-Me-5-VIm). These results showed that the rate enhancement exhibited by the polymer was due entirely to a favorable entropy term.     

Esterolytic activity of imidazole-containing polymers. Synthesis and characterization of copoly[1-alkyl-4- or 5-vinylimidazole/4(5)-vinylimidazole] and its catalytic activity in the hydrolysis of p-nitrophenyl acetate

The water-soluble monomers, 1-methyl-4-vinylimidazole, 1-methyl-5-vinylimidazole, 1-ethyl-5-vinylimidazole, and 1-propyl-5-vinylimidazole have been synthesized, polymerized, and copolymerized with 4(5)-vinylimidazole. The copolymers were characterized by ¹⁴C-labeling, NMR, pK_a determination and viscosity measurements. The monomer reactivity ratios determined by ¹⁴C counting are r₁ = 1.04; r₂ = 0.94 [M₁ = 4(5)-vinylimidazole, M₂ = 1-methyl-4-vinylimidazole] and r₁ = 1.01; r₂ = 0.86 [M₁ = 4(5)-vinylimidazole, M₂ = 1-methyl-5-vinylimidazole]. The esterolytic activity of the copolymers for the hydrolysis of p-nitrophenyl acetate (PNPA) at pH 7–8 in 28.5% ethanol–water was higher than that of the mixtures of homopolymers. At pH 5–6 the esterolytic activities of the copolymers and the mixtures were similar. The most efficient esterolytic activity for PNPA hydrolysis at pH 7.11 in 28.5% ethanol–water occurred for copolymers containing 75 mole % 4(5)-vinylimidazole and for copolymers containing 1-methyl-4-vinylimidazole rather than 1-methyl-5-vinylimidazole.     

Esterolytic activity of imidazole-containing polymers. Hydrophobic influences in copoly[1-alkyl-4- or 5-vinylimidazole/4(5)-vinylimidazole]-catalyzed hydrolysis of 3-nitro-4-acyloxybenzoic acids

Water-soluble copolymers containing imidazole and N-alkylated imidazole pendant groups have been synthesized in order to investigate the hydrophobic interactions between polymeric catalysts and long alkyl chain ester substrates. Copoly[1-methyl-4-vinyl-imidazole/4(5)-vinylimidazole],copoly[1-methyl-5-vinylimidazole/4(5)-vinylimidazole], copoly[1-ethyl-5-vinylimidazole/4-(5)-vinyl-imidazole] and copoly[1-propyl-5-vinylimidazole/4(5)-vinylimidazole] were synthesized and their catalytic activity toward 3-nitro-4-acyloxybenzoic acid substrates (S_n^?) was determined in 28.5% ethanol–water and in water and compared with that of the mixtures of homopolymers. Hydrophobic interactions were important for rate enhancement of the hydrolysis of long-chain ester substrates compared to that of short-chain ester substrates. The copolymers catalyzed the hydrolysis of 3-nitro-4-dodecanoyloxy-benzoic acid (S₁₂^?) about two times faster than the mixtures at pH 7.11 in 28.5% ethanol–water. The hydrolysis of S₁₂^? by the copolymers was about five times faster in water than 28.5% ethanol–water.     

Synthesis and esterolytic reactions of linear and cross-linked asymmetric imidazole-containing polymers

Asymmetric linear and cross-linked imidazole-containing polymers were prepared from 1-[2(S)-methylbutyl]-4-vinylimidazole and 1-[2(S)-methylbutyl]-5-vinylimidazole. The esterolytic reactions of these linear and cross-linked asymmetric polymers with the enantiomeric substrates (R)- and (S)-4-(3-methylpentadecanoyl)-3-nitrobenzoic acid, (R)- and (S)-S, were studied by measuring the pseudo-first order kinetics of the solvolysis of these enantiomeric substrates in the presence of these asymmetric polymers. The linear homopolymers and copolymers of 1-[2(S)-methylbutyl]-4- and 5-vinylimidazole showed hydrophobic and electrostatic effects in the solvolysis of the enantiomeric substrates with these linear asymmetric polymers. Cross-links were introduced into these asymmetric polymers to increase the rigidity and reduce the number of conformations available to the polymer. The reduced conformational mobility was expected to enhance any enantioselectivity in the solvolysis of the enantiomeric substrates with these polymers. Using these cross-linked polymers, hydrophobic interactions were observed in the solvolysis of a series of substrates with increasing alkyl chain length. Also, on changing the polarity of the solvent, a bell-shaped rate profile was observed in the solvolysis of the long chain substrate S. This effect was attributed to a combination of the coiling of the cross-linked polymer chains and hydrophobic interactions with the substrate on changing solvent polarity. Even with the increased rigidity of these cross-linked polymers, no significant enantioselectivity in the solvolysis of the enantiomeric substrates was observed. So, neither the linear nor the cross-linked asymmetric polyvinylimidazoles showed enantioselectivity in the solvolysis of these enantiomeric substrates. In this case, the hydrophobic interactions and the reduced conformational mobility through crosslinking were not strong enough to bring about enantioselectivity in the solvolysis of these enantiomeric substrates.     

Reactions and polymerization of 1-trityl-4-vinylimidazole

1-Trityl-4-vinylimidazole was prepared by direct tritylation of 4(5)-vinylimidazole and polymerized using a free radical initiator. Poly(1-trityl-4-vinylimidazole) was hydrolyzed using aqueous acetic acid to give poly[4(5)-vinylimidazole]. The poly[4(5)-vinylimidazole], which was obtained from the hydrolysis of poly(1-trityl-4-vinylimidazole), was compared with poly[4(5)-vinylimidazole] prepared directly from 4(5)-vinylimidazole for differences in stereochemistry. The stereochemistry of both polymers was found to be similar by high-resolution NMR. Thus, the trityl does not influence the stereochemistry of poly[4(5)-vinylimidazole]. The reaction of 1-trityl-4-vinylimidazole with n-butyllithium gave 2-lithio-1-trityl-4-vinylimidazole. This intermediate was used to prepare 2-substituted 4(5)-vinylimidazoles, which are new monomers that can be polymerized using free radical initiators.     

Polymeric catalysis: Imidazoles grafted onto poly(vinylamine). II. Kinetics of the esterolysis of activated phenyl esters

In the previous paper, some ω-(1-imidazolyl) and ω-[4(5)-imidazolyl]alkanoic acids were synthesized and grafted onto poly(vinylamine). These water soluble catalysts of varying apolarity contain both hydrophobic and electrostatic binding sites for neutral and charged substrates. The influence of side chain length, percent graft, and the substitution in the imidazole ring are described. The grafts possessing the longer side chains and lesser apolar weight were more efficient catalysts than the grafts containing numerous short side chains and greater apolar weight. These grafts exhibited slower rates than poly[4(5)-vinylimidazole].     

The Influence of Reaction Conditions on the Copolymer Composition in Inverse Miniemulsion

Summary: Water-soluble poly(2-acrylamido-2-methylpropane-1-sulfonic acid-co-1-vinylimidazole) (P(AMPS-co-1-VIm)) and poly(2-acrylamido-2-methylpropane-1-sulfonic acid-co-2-(dimethylamino)ethyl methacrylate (P(AMPS-co-DAMA)) are studied as it is known that the copolymer composition is affected by pH of the monomer phase in inverse miniemulsion. The distribution of the basic monomers in the continuous and dispersed phase changes due to their degrees of protonation. The amounts of the monomers in the cyclohexane phase is determined by gas chromatography, the copolymer composition is studied by elemental and thermogravimetric analysis. An insight into the monomer distribution in the polymer is provided by simultaneous potentiometric and conductometric titration of polymer solutions.     

An unexpected palladium-catalyzed cyclization of bis-hydroxy allylic alcohols to dioxabicyclo[2.2.2]octanes

The palladium(II)-catalyzed cyclization of bis-hydroxy allylic alcohols afforded quantitatively a mixture of (3-alkyl-5-vinyltetrahydrofuran-3-yl)methanol and 4-alkyl-1-methyl-2,6-dioxabicyclo[2.2.2]octane.     

Compounds of imidazoles with ruthenium(III) chloride

Summary Reaction of ruthenium(III) chloride with imidazole(Im) and different substituted imidazoles,viz. N-methylimidazole (N-MeIm), 2-methylimidazole(2-MeIm), 4-methylimidazole (4-MeIm),N-vinylimidazole(N-VIm), 2-methyl- 1-vinyl-imidazole(2-Me-1-VIm), 1,2-dimethylimidazole(1,2-Me,Im), 2-ethylimidazole(2-EtIm) and 2-ethyl-4(5)-methylimidazole (2-Et-4(5)-MeIm] yield products of the types [Ru₂L₄Cl₆] · 2 H₂O (L = N-VIm or 4-MeIm), [Ru₂L₄Cl₆] · 4 H₂O (L = Im or 2-Et-4(5)-MeIm), [Ru₂L ³ (H₂O)Cl₆] (L =N-MeIm or 2-MeIm), [Ru₂L ² (H₂O)₂Cl₆] (L = 1,2-Me₂Im or 4-MeIm), [Ru(2-Me-1-VIm)₃Cl₃] · H₂O and [Ru(2-EtIm)₃(H₂O)Cl₂]. These compounds were characterised by elemental analyses, conductometric measurements, i.r. and electronic spectral analyses. Magnetic moments range from 1.01 to 1.9 B.M. The e.s.r. spectra and g values of some of the compounds are indicative of high distortion.     

Heterocyclic compounds from 3,3-dimercapto-1-aryl-2-propen-1-ones. Note 3. Condensation with N-methyl-o-phenylenediamine and N-benzyl-o-phenylenediamine

Two seven-membered ring compounds and three five-membered ring compounds were obtained by reaction in hot xylene of 3,3-dimercapto-l-phenyl-2-propen-1-one (1) with N-alkyl-o-phenylenediamines (2) . Compounds isolated were the 4-phenyl-5-alkyl-1,5-dihydro-2H-1,5-benzodiazepine-2-thiones (3) the 1-alkyl-4-phenyl-1,3-dihydro-2H-1,5-benzodiazepine-2-thiones (4) , the 1-alkyl-2-phenacylbenzimidazoles (5) , the 1-alkyl-2-phenylbenzimidazoles (6) and the 1-alkyl-2-methylbenzimidazoles (7) . The structures of these compounds were elucidated from their chemical reactivity and their nmr and ir spectra.     

Optimization strategies for radiation induced grafting of 4-vinylpyridine onto poly(ethylene-co-tetraflouroethene) film using Box-Behnken design

The radiation induced grafting of 4-vinylpyridine (4-VP) onto poly(ethylene-co-tetrafluoroethene) (ETFE) was optimized using the Box-Behnken factorial design available in the response surface method (RSM). The optimized grafting parameters; absorbed dose, monomer concentration, grafting time and reaction temperature were varied in four levels to quantify their effect on the grafting yield (GY). The validity of the statistical model was supported by the small deviation between the predicted (GY=61%) and experimental (GY=57%) values. The optimum conditions for enhancing GY were determined at the following values: monomer concentration of 48 vol%, absorbed dose of 64 kGy, reaction time of 4 h and temperature of 68 °C. A comparison was made between the optimization model developed for the present grafting system and that for grafting of 1-vinylimidazole (1-VIm) onto ETFE to confirm the validly and reliability of the Box-Behnken for the optimization of various radiation induced grafting reactions. Fourier transform infrared (FTIR), thermogravimetric analysis (TGA) and X-ray diffraction (XRD) were used to investigate the properties of the obtained films and provide evidence for grafting.     

A diastereoselective synthesis of both quercus lactone isomers employing allyl-type organometallics as key intermediates

Consecutive treatment of endo-butenyl potassium or endo-1-(tetrahydropyranyloxy)-exo-butenyl lithium with fluorodimethoxyboron and pentanal at ?75°C affords an erythro- and, respectively, threo-adduct, the hydrolysis and oxidation of which leads to the cis- and, respectively, trans-isomer of 5-butyl-4-methyl-tetrahydro-2-furanone (4-butyl-3-methyl-4-butanolide), 1, the so-called quercus or oak lactones.     

Synthesis,characterization, and antioxidant activity of heterocyclic Schiff bases

Schiff base derivatives have gained great importance due to revealing a great number of biological properties. Schiff bases were synthesized by treatment of 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 1 ) with various aldehydes in methanol at reflux. In addition, diamine was reacted with an aldehyde to yield the corresponding Schiff bases. The structures of synthesized Schiff bases were elucidated by spectroscopic methods such as microanalysis, ¹H-NMR, ¹³C-NMR, and FTIR. Antioxidant activities of synthesized Schiff bases were carried out using different antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH^•) scavenging, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, and reducing power activity. (E)-4-((1H-indol-3-yl)methyleneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 3 ), (E)-1,5-dimethyl-4-((2-methyl-1H-indol-3-yl)methyleneamino)-2-phenyl-1H-pyrazol-3(2H)-one ( 5 ), (E)-1,5-dimethyl-2-phenyl-4-(thiophen-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 7 ), (E)-1,5-dimethyl-2-phenyl-4-(quinolin-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 9 ), (1S,2S,N1,N2)-N1,N2-bis((1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 11 ), and (1S,2S,N1,N2)-N1,N2-bis((2-methyl-1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 12 ) were synthesized in high yields. Compound 5 displayed a good ABTS^•+ activity. Compound 3 revealed the outstanding activity in all assays. Compound 7 has the best-reducing power ability in comparison to other synthesized compounds. Although compounds 5, 11, 12 are new, compounds 3, 7, 9 are known. Due to revealing a good antioxidant activity, the synthesized compounds ( 3, 5, 7 ) have the potential to be used as synthetic antioxidant agents.     

Dual CCK-A and CCK-B receptor antagonists (II). Preparation and structure activity relationships of 5-alkyl-9-methyl-1,4-benzodiazepines and discovery of FR208419

In our continuing research for dual CCK-A and -B antagonists, according to our hypothesis that dual CCK-A and -B antagonists should be more efficacious than selective CCK-A antagonists for the treatment of pancreatitis, we have prepared various 5-alkyl-9-methyl-1,4-benzodiazepines. From the compounds prepared, 1-cyclohexyl-carbonylmethyl-5-ethyl-9-methyl-3- (m-tolylureido)-2-oxo-1,4-benzodiazepine, (40) was selected as a candidate for development due to its well-balanced high affinity for both receptors. The R-enantiomer of 40, (R)-40 (FR 208419), had 27-fold higher affinity for the CCK-A receptor and 8-fold more potent CCK-B receptor binding activity than (S)-40. The biological activity after p.o. administration of (R)-40, estimated from the ID50 value (0.23 mg/kg p.o.) obtained by preliminary evaluation by gastric emptying effects, is considered to be high enough for further development. This compound is now undergoing further biological evaluations with a view to clinical development.     

2-甲基-1,5-苯并硫氮杂的基态和激发态反应的研究 I: 2-甲基-1,5-苯并硫氮杂-4(5H)-酮的卤化和亲核取代反应

2-甲基-1,5-苯并硫氮杂-4(5H)-酮(1a)与不同的氯化试剂-五氯化磷、三氯氧磷和氯化砜在不同的条件下氯化,可分别生成:2-甲基-4-氯-1,5-苯并硫氮杂(2a)、2-氯-4-甲基-1,5-苯并硫氮杂(3a)、2-二氯甲基苯并噻唑(5)、2-三氯甲基苯并噻唑(6)和2-甲基-1,5-苯并硫氮杂-4(5H)-酮盐酸盐(4).2-甲基-4-氯-1,5-苯并硫氮杂与醇钠反应生成相应的2-甲基-4-烷氧基-1,5-苯并硫氮杂外,还可以分离到它的2,4-异构体,2-烷氧基-4-甲基-1,5-苯并硫氮杂.产物的结构均经元素分析、红外光谱、^1H和^1^3C核磁共振谱和质谱鉴定.     

Preparation and characterization of poly(m-xylylene oxamide) and its copolymer

New polyoxamides, poly(m-xylylene oxamide) (PMXD2) and its copolymer with 2-methyl-1,5- pentanediamine (P(MXD2/M52)) with relative viscosity up to 4.6 were synthesized via spray/solid state polymerization. The obtained polyoxamides were characterized by FTIR, NMR, WAXD, DSC and TGA. The T_m of the copolymers decreased with increasing percentage of poly(2-methyl-1,5- pentaneoxamide) (PM52) in the copolymer from 346°C for 100% poly(meta-xylyleneoxamide) (PMXD2) to 277°C for copolymers of PMXD/PM52 (60/40). TGA analysis revealed that the thermal stability of the copolymers compared well with commercial PA6 and XRD studies suggested the copolymers possessed high crystallinity. DMA profile of the PMXD/PM52 (70/30) copolymer showed better mechanical performance with a storage modulus of about 7.2 GPa as compared to 1.8 GPa of PA6 at 25°C.     

Compounds of palladium halides with substituted imidazoles

Summary Compounds of the type PdL₂X₂ (L=1-methylimidazole, 1-vinylimidazole, 1-n-butylimidazole, 1,2-dimethylimidazole, 1-vinyl-2-methylimidazole, 1,2-dimethyl-5-nitroimidazole, 2-isopropyl-4(5)-nitroimidazole and 2-methyl-4(5)-nitro-imidazole; X=Cl or Br) are obtained by treating PdX₂ (1 mole) with solutions of the ligands L (2 moles). An excess of L gives PdL₄X₂ complexes (L=1-methylimidazole, 1-vinylimidazole, 1,2-dimethylimidazole and 1-vinyl-2-methylimidazole). The compounds were characterized by chemical analyses, molar conductivity measurements and i.r. spectra.     

Mn(III)-initiated facile oxygenation of heterocyclic 1,3-dicarbonyl compounds

The Mn(III)-initiated aerobic oxidation of heterocyclic 1,3-dicarbonyl compounds, such as 4-alkyl-1,2-diphenylpyrazolidine-3,5-diones, 1,3-dialkylpyrrolidine-2,4-diones, 3-alkyl-1,5-dimethylbarbituric acids, and 3-butyl-4-hydroxy-2-quinolinone gave excellent to good yields of the corresponding hydroperoxides, which were gradually degraded by exposure to the metal initiator after the reaction to afford the corresponding alcohols. The synthesis of 30 heterocyclic 1,3-dicarbonyl compounds, the corresponding hydroperoxides and the 10 alcohols, their characterization, and the limitations of the procedure are described. In addition, the mechanism of the hydroperoxidation and the redox decomposition of the hydroperoxides are discussed.     

α-Alkylation of Amino Acids without Racemization. Preparation of Either (S)- or (R)-α-Methyldopa from (S)-Alanine

Enantiomerically pure cis- and trans-5-alkyl-1-benzoyl-2-(tert-butyl)-3-methylimidazolidin-4-ones ( 1, 2, 11, 15, 16 ) and trans-2-(tert-butyl)-3-methyl-5-phenylimidazolidin-4-one ( 20 ), readily available from (S)-alanine, (S)-valine, (S)-methionine, and (R)-phenylglycine are deprotonated to chiral enolates (cf. 3, 4, 12, 21 ). Diastereoselective alkylation of these enolates to 5,5-dialkyl- or 5-alkyl-5-arylimidazolidinones ( 5, 6, 9, 10, 13a-d, 17, 18, 22 ) and hydrolysis give α-alkyl-α-amino acids such as (R)- and (S)-α-methyldopa ( 7 and 8a , resp.), (S)-α-methylvaline ( 14 ), and (R)-α-methyl-methionine ( 19 ). The configuration of the products is proved by chemical correlation and by NOE ¹H-NMR measurements (see 23, 24 ). In the overall process, a simple, enantiomerically pure α-amino acid can be α-alkylated with retention or with inversion of configuration through pivaladehyde acetal derivatives. Since no chiral auxiliary is required, the process is coined ‘self-reproduction of a center of chirality’. The method is compared with other α-alkylations of amino acids occurring without racemization. The importance of enantiomerically pure, α-branched α-amino acids as synthetic intermediates and for the preparation of biologically active compounds is discussed.     

Fused s-triazino heterocycles. VIII. 1,3,4,6,9b-pentaazaphenalenes. Reactions of a methyl and bromomethyl side chain

Enhanced reactivity of the methyl group of 2-t-butyl-5-methyl-1,3,4,6,9b-pentaazaphenalene allowed acetic anhydride-catalyzed condensation reactions with several aromatic aldehydes, and base-catalyzed alkylation reactions with several alkyl halides to take place, albeit in low yields. Of the many nucleophiles tried, only salts of carboxylic acids, in the presence of 18-crown-6, were able to displace bromine from 2-(bromomethyl)-5-methyl-1,3,4,6,9b-pentaazaphenalene.