13C-NMR Spectra of 2- and 3-Phthalimido-3(2)-Benzimidazolylpropanoic Acid and 2- and 3-Phthalimidobenzimidazopyrrolone,Reaction Products of Phthaloylaspartic Anhydride with Ortho-Phenylenediamine

Two pairs of isomers of 3- and 2-phthalimido-3(2)benzimidazolylpropanoic acid (V and VI) and 2- and 3-phthalimidobenzimidazopyrrolone (VII and VIII) were produced from the reaction of phthaloylaspartic anhydride (I) with o-phenylenediamine (II). The ¹³C-NMR spectra of V and VI both showed 11 carbon signals indicating that the structures of their benzimidazole groups were symmetric. Isomers V and VI were easily distinguished from each other by the chemical-shift-differences (Δδ) of the methylene carbon and the methine carbon. Compounds VII and VIII displayed 14 carbon signals and no longer showed the symmetric structure of the benzimidazole moity, The chemical-shift-differences (Δδ) between methylene carbon and methine carbon in pyrrolones of VII and VIII can also be used to distinguish VII from VIII. The Δδ of compound VII is less than that of compound VIII.     

Nucleosides. CIX. 2′-Deoxy-ψ-isocytidine, 2 -deoxy-ψ-uridine,and 2′-deoxy-l-methyl-ψ-uridine. Isosteres of deoxycytidine,deoxyuridine and thymidine

2′-Deoxy-ψ-isocytidine (VIIβ), a 2′-deoxy analog of antileukemic ψ-isocytidine and also a C-nucleoside analog of deoxycytidine, was synthesized from ψ-uridine by making use of the newly discovered pyrimidine to pyrimidine transformation reaction [J. Chem. Soc., 14, 537 (1977)]. 2′-Deoxy-ψ-uridine (IIβ) and 2′-deoxy-l-methyl-ψ-uridine (V), both C-nucleoside analogs of deoxyuridine and thymidine, were also synthesized. ψ-Uridine was converted into the 2′-chloro analogs (I) which was reduced with tributyltin hydride to give an α,β-mixture of 2′-deoxy-ψ-uridines. The β-isomer (11β was trimethylsilylated and the product (III) treated with methyl iodide to afford the 1-methyl derivative (IV). After hydrolytic removal of the trimethylsilyl groups from IV, the thymidine analog (V) was obtained in good yield. A crude mixture of II was converted in good yield into an α,β-mixture of 1,3-dimethyl-2 -deoxy-ψ-uridines (VI) by treatment with DMF dimethyl acetal in DMF. Treatment of the β-isomer (VIβ) with guanidine, however, gave the α,β-mixture of 2 -deoxy-ψ-isocytidines (VII). The pure β-isomer (VIIβ) was obtained by thick layer chromatography. The pure α-isomer (VIIα) was obtained when VIα was treated with guanidine. 2 -Deoxy-ψ-isocytidine (VIIβ) and 2 -deoxy-l-methyl-ψ-uridine (V) exhibited inhibitory activity against P815 cells (ID_{5 0} 1.2 μg./ml. and 4.9 μg./ml., respectively) and the thymidine analog V was found to be active against Streptococcus faecium var. duran. J. Heterocyclic Chem., 14, 1119 (1977)     

Oligomeric cholates: amphiphilic foldamers with nanometer-sized hydrophilic cavities

The hydroxyl at the C-3 of cholic acid was converted to an amino group, and the resulting amino-functionalized cholic acid was used as a monomer to prepare amide-linked oligomeric cholates. These cholate oligomers fold into helical structures with nanometer-sized hydrophilic internal cavities in solvent mixtures consisting of mostly nonpolar solvents such as carbon tetrachloride or ethyl acetate/hexane and 2-5% of a polar solvent such as methanol or DMSO. The conformations of the foldamers were studied by UV, fluorescence, fluorescence quenching, and fluorescence resonance energy transfer. The nature of the polar/nonpolar solvents and their miscibility strongly influenced the folding reaction. Folding was cooperative, as evidenced by the sigmoidal curves in solvent denaturation experiments. The folded conformers became more stable with an increase in the chain length. The folding/unfolding equilibrium was highly sensitive toward the amount of polar solvent. One percent variation in the solvent composition could change the folding free energies by 0.5-1.4 kcal/mol.     

Exciplex and radical ion intermediates in the photochemical reaction of 9-cyanophenanthrene with 2,3-dimethyl-2-butene

The photochemical reaction of 9-cyanophenanthrene and 2,3-dimethyl-2-butene, first reported by Mizuno, Pac and Sakurai, has been reinvestigated. The formation of a [2+2]-cycloadduct via a singlet exciplex is the exclusive reaction in the nonpolar solvents benzene and ethyl acetate. Photochemical behavior in polar solvents is far more complicated than previously reported. Mechanisms consistent with the effects of solvent polarity, methanol concentration, methanol deuteration, and light intensity upon product yields are proposed. Formation of a 9-cyanophenthrene anion radical and 2,3-dimethyl-2-butene cation radical is the primary photoinitiated process in polar solvent. The cation radical can undergo deprotonation to yield an allyl radical or nucleophilic attack by methanol to yield a methoxyalkyl radical. Covalent bonding of these radicals and the 9-cyanophenanthrene anion radical gives rise to the acyclic adducts obtained in polar solvents. The anion radical can also be protonated, leading ultimately to the formation of 9,10-dihydro-9-cyanophenanthrene.     

Mixed anhydrides in peptide synthesis. Influence of the solvent and the amine on the racemization of dmet residue of an enkephalin sequence

A comparative study on the effectiveness of all possible anune/solvent combination with three different solvents (THF, DCM, DMF) and three different bases (NMM, NMPi, NMPo) in avoiding the racemization of the DMet residue during a mixed anhydride coupling has been carried out. The results show that the best combination is THF/NMM. Though, when more polar solvents are required, the system DMF/NMPo is recommended.     

Syntheses of polyimide copolymers based on N,N′-(pyromellitoyl)diglycine

N,N′-(pyromellitoyl)diglycine ( 1 ) was synthesized by reacting pyromellitic anhydride with glycine in polar solvents such as DMAC, NMP, or DMF at 60°C and then refluxed azeotropically with toluene. Among these solvents, it is easy to form DMF-insoluble salt ( 1 ″) in DMF, but this salt can be converted to 1 by treating first with NaHCO₃ and then with HCl. Reacting monomer N,N′-(pyromellitoyl)diaminoacetyl chloride ( 2 ) can be obtained by treating with thionyl chloride, and N,N′-(pyromellitoyl)dimethyl aminoacetate ( 3 ) can be obtained by treating 2 with methanol. As 2 reacts with aromatic diamine in polar solvents, such as DMAC, DMF, or NMP, a series of copolypyromellitimide amides ( 5a–h ) can be obtained. These copolymers can be processed by using DMAC + LiCl (5%) as solvent to produce flexible film of good weather resistivity and heat resistivity. Monomer 2 can also react with aromatic dihydrazides in polar solvents to produce copolypyromellitimide hydrazides ( 6a–c ), and 6a–b can be condensated again to produce copolypyromellitimide oxadiazoles ( 7a–b ) in polyphosphoric acid (PPA). Besides, 3 reacts with aromatic tetraamine by carrying out polycondensation in PPA to produce copolypyromellitimide benzimidazole ( 8 ). Structures of copolymers mentioned above were identified by comparing IR spectra with those of model compounds. Heat resistivity was measured by the thermogravimetric method, and their solubilities in various solvents were also investigated.     

Aromatic polyesterimides

Several novel arylene bis(trimellitate) dianhydrides have been prepared by: the acidolysis reaction of trimellitic anhydride (TMA) with aromatic diacetoxy compounds and the reaction of trimellitic anhydride monoacid chloride with diphenols. These novel aromatic bisesteranhydrides were reacted with aromatic diamines in polar solvents to give high molecular weight polyamic acid solutions. Heat converted these soluble precursors to insoluble aromatic polyesterimides having good physical and thermal properties. The mechanism of the acidolysis reaction between an aromatic acid and an aromatic acetoxy compound is briefly discussed.     

Solute–Solvent Interactions of Methyl Violet in Different Solvents on Spectral Data

Spectroscopic studies of Methyl violet in protic (water, methanol, ethanol, isopropanol and n-butanol) and aprotic solvents (acetone, DMF) were carried out. UV-Visible absorption spectra of Methyl violet in protic solvents showed a hypsochromic shift, as the solvent polarity was changed from less polar to more polar, while a bathochromic shift was observed for aprotic solvents. Transition energy of Methyl violet in different solvents was correlated with solvatochromic parameters to study solute–solvents interactions. The Kamlet–Taft, Catalan and unified scale models were applied to investigate interactions between Methyl violet and solvents. The best agreement is found for the Catalan model.     

Engineering the promiscuous racemase activity of an arylmalonate decarboxylase

Variant G74C of arylmalonate decarboxylase (AMDase) from Bordatella bronchoseptica has a unique racemising activity towards profens. By protein engineering, variant G74C/V43A with a 20-fold shift towards promiscuous racemisation was obtained, based on a reduced activity in the decarboxylation reaction and a two-fold increase in the racemisation activity. The mutant showed an extended substrate range, with a 30-fold increase in the reaction rate towards ketoprofen. Molecular dynamics simulations and the substrate profile of the racemase indicate that the steric and polar effects of the substrate structure play a more dominant role on catalysis than mere kinetic α-proton acidity. The observation that the conversion of β,γ-unsaturated carboxylic acids does not lead to a rearrangement to form their α,β isomers indicates a concerted rather than a stepwise mechanism. Interestingly, a substrate bearing a nitro group instead of the carboxylic acid group on the α-carbon atom was also converted by the racemase.     

AN EXAMPLE OF HOW PHOTOPHYSICAL PROPERTIES CAN INFLUENCE THE MAGNITUDE OF SOLVENT ISOTOPE EFFECTS UPON PHOTO-OXIDATION REACTIONS

Abstract Substantial isotope effects have been observed for the dye sensitised photo-oxidation of 1,3-diphenyl-2-pyrazoline in both polar and non polar solvents, implicating singlet oxygen as a reactive intermediate. By way of contrast, a solvent isotope effect upon the direct photo-oxidation of the pyrazoline was only observed when a protic solvent (methanol) was used. It was found that the photophysical properties (e.g. quantum yields and fluorescence lifetimes) of pyrazolines are sensitive to the isotopic composition of protic solvents but not aprotic solvents. The solvent isotope effect observed for the direct photo-oxidation reaction in methanol may not therefore be a true indication of the participation of singlet oxygen. Since this reaction may not be singlet oxygen mediated, an alternative mechanism is proposed.     

Ring-opening of tertiary cyclopropanols derived from β-diketones

The ring-opening reaction of 1,2-disubstituted cyclopropanols, prepared from β-diketones, mediated by Cu(NO₃)₂, p-TsOH, and NaOH is reported. The Cu(II)-mediated ring-opening of cyclopropanols gave α-methylene-γ-diketones in good yields. The reaction took place at the less substituted carbon of the cyclopropanols, involving mild conditions and a simple procedure. The reaction induced by p-TsOH in CH₂Cl₂ afforded α-methyl-γ-diketones as the major product with minor amounts of δ-diketones. The 2,3,5-trisubstituted furans were obtained in high yields when the ring-opening reaction was mediated by p-TsOH in methanol under reflux conditions. In the presence of sodium hydroxide the reaction proceeded smoothly in preference to the formation of δ-diketones, particularly for substrates with an aromatic group on the cyclopropane.     

Polarity‐Dependent Isomerization of an Unsymmetrical Overcrowded Ethylene Promoted by Zwitterionic Contribution in the Twisted Isomer

The twisted form of bianthrone is known as a metastable state provided by a photo‐induced or thermal‐induced isomerization of the folded form, and thus prevents the isolation and the detailed analysis of its electronic structure. In this study, an unsymmetrical bianthrone ( 2 ), consisting of the electron‐withdrawing anthrone and electron‐donating acridane, have been synthesized and shown to exhibit a solvent‐polarity‐dependent isomerization reaction between the folded and twisted isomers. With increasing the polarity of the solvent, 2 showed an isomerization reaction from the folded form to the twisted form. The stabilization of the twisted isomer in polar solvents can be interpreted as proof of its relatively large zwitterionic character. The DMF solution of 2 displayed paramagnetically‐broadened NMR signals from the thermally populated triplet state resulting from rotation of the weakened ethylenic double bond of the twisted isomer.     

用气相色谱法研究乙酸乙烯酯不对称氢甲酰化反应中溶剂的影响

用毛细管气相色谱、色－质谱和旋光色散及圆二色性谱仪等方法对乙酸乙烯酯在非极性和极性溶剂中的不对称氢甲酰化反应产物进行分离和鉴定。实验结果表明,在非极性溶剂中反应的收率、选择性、光学收率ｅ．ｅ．值（ｅｎａｎｔｉｏｍｅｒｉｃｅｘｃｅｓｓ）均比极性溶剂中的结果为好。由此探讨了不对称氢甲酰化反应中溶剂的影响。     

Kinetics and mechanism of urethane formation catalyzed by organotin compounds. II. The reaction of phenyl isocyanate with methanol in DMF and cyclohexane under the action of dibutyltin diacetate

The kinetics of the dibutyltin diacetate (DBTDA)-catalyzed reaction of phenyl isocyanate with methanol in DMF and cyclohexane have been studied by monitoring the rate of change of the absorbance of the reaction mixture at 281.6 and 280.9 nm, respectively. Our results indicate that the mechanism of the reaction is independent of the nature of the (inert) solvent. The subsequent reaction steps are (i) complexation of methanol to DBTDA, (ii) dissociation of the complex into a proton and an anion of composition [(n-C₄H₉)₂Sn(OCOCH₃)₂(OCH₃)]^?, (iii) insertion of the isocyanate into the tin—alkoxy bond (the rate-determining step), and (iv) methanolysis of the thus-formed urethane precursor with simultaneous regeneration of the anion. The rate of the catalyzed reaction increases on goin from coordinating to noncoordinating solvents. The following sequence in order of increasing rate constant was observed: DMF < dibutyl ether < cyclohexane. This is because in coordinating solvents, DBTDA and methanol, apart from forming a complex with each other, also form complexes with the solvent.     

Reaction of β-aeylarylhydrazines with dimethylformamide in the presence of calcium hydride. A novel route to 3-pyrazolin-5-ones

Reaction of β-acylarylhydrazines with calcium hydride in refluxing dimethylformamide (DMF) was found to lead to the formation of 2-aryl-3-pyrazolin-5-ones (V). Application of this novel synthetic method resulted in fair to good yields of a series of 2,4-diaryl-3-pyra7,olin-5-ones. The infrared spectra (potassium bromide) of the products (V) showed that these compounds exist as the laetim tautomer (VI). An oxindole (IIc) was obtained when dimethylbenzamide was substituted for DMF under similar reaction conditions.     

5-烷氧基-3,4-二卤-2(5H)-呋喃酮与不饱和胺的反应研究

为了深入探索5-烷氧基-3,4-二卤-2(5H)-呋喃酮与胺类试剂发生的反应,进一步在氟化钾作催化剂和四氢呋喃作溶剂的条件下,研究了其与系列不饱和胺的反应,通过旋光度,UV-Vis,IR,1H NMR,13C NMR,MS,元素分析和X射线单晶衍射等表征方法对产物进行结构表征,发现大多数情况下发生预期的串联迈克尔加成-消除反应,得到了16个新的β-胺基-2(5H)-呋喃酮化合物.当不饱和胺为空间位阻较大的2,5-二甲基-3-吡咯啉时,与位阻较大的5-孟氧基-3,4-二卤-2(5H)-呋喃酮反应只是生成异常的2(5H)-呋喃酮开环产物,而与位阻较小的5-甲氧基-3,4-二卤-2(5H)-呋喃酮反应则既有正常的β-胺基-2(5H)-呋喃酮产物,也有经开环重排反应的机理得到的异构体产物.后者表明,底物的位阻大小也是影响反应的因素,甚至导致同时存在竞争反应.     

Effect of Confinement on the Properties of Sequestered Mixed Polar Solvents: Enzymatic Catalysis in Nonaqueous 1,4‐Bis‐2‐ethylhexylsulfosuccinate Reverse Micelles

The influence of different glycerol, N,N‐dimethylformamide (DMF) and water mixtures encapsulated in 1,4‐bis‐2‐ethylhexylsulfosuccinate (AOT)/n‐heptane reverse micelles (RMs) on the enzymatic hydrolysis of 2‐naphthyl acetate by α‐chymotrypsin is demonstrated. In the case of the mixtures with DMF and protic solvents it has been previously shown, using absorption, emission and dynamic light‐scattering techniques, that solvents are segregated inside the polar core of the RMs. Protic solvents anchor to the AOT, whereas DMF locates to the polar core of the aggregate. Thus, DMF not only helps to solubilize the hydrophobic substrate, increasing its effective concentrations but surprisingly, it does not affect the enzyme activity. The importance of ensuring the presence of RMs, encapsulation of the polar solvents and the corrections by substrate partitioning in order to obtain reliable conclusions is highlighted. Moreover, the effect of a constrained environment on solvent–solvent interactions in homogenous media and its impact on the use of RMs as nanoreactors is stressed.     

Derivatives of the thiazolo[2,3-a]isoquinolinium system

The ketosulfides (IV) formed by the reaction of α-bromoketones with 2α-thiohomo-phthalimide (II) have been cyclized to form hydrogen-bonded, dimeric hemiperchlorates (V). Alternative products from the cyclization, 2-[2′-(carboxymethyl)phenyl]thiazoles (VII), may be cyclized with acetic anhydride to O-betaines (VI). The same betaines are obtained from the hemiperchlorates (V) by deprotonation. The ketosulfide hydrobromides (XIII) from α-bromoketones and 1-thio-3, 4-dihydroisocarbostyril (XII) give 5,6-dihydro-thiazolo[2,3-a]isoquinolinium salts (XV) on cyclization.     

KINETIC STUDY OF CARBONYLATION OF METHANOL TO ACETIC ACID AND ACETIC ANHYDRIDE OVER A NOVEL COPOLYMER-BOUND CIS-DICARBONYLRHODIUM COMPLEX

The kinetic study of carbonylation of methanol-acetic acid mixture to acetic acid and acetic anhydride over a cis-dicarbonylrhodium complex (MVM' Rh) coordinated with the ethylene diacrylate (M') crosslinked copolymer of methyl acrylate (M) and 2-vinylpyddine (V)shows that the rate of reaction is zero order with respect to both reactants methanol and carbon monoxide, but first order in the concentrations of promoter methyl iodide and rhodium in the complex. Polar solvents can accelerate the reaction. Activation parameters were calculated from the experimental results, being comparable to that of the homogeneous system. A mechanism similar to that of soluble rhodium catalyst was proposed.     

Mechanism of charge-transfer polymerization. V. Photopolymerization and photocyclodimerization of N-vinylcarbazole in the N-vinylcarbazole–oxygen–solvent system

Photochemical reactions of N-vinylcarbazole (VCZ), studied in various solvents, were profoundly influenced by the atmosphere. In the deaerated system radical polymerization of VCZ occurred in various solvents, e.g., tetrahydrofuran, acetone, ethyl methyl ketone, acetonitrile, methanol, sulfolane, N,N-dimethylformamide (DMF), or dimethyl sulfoxide (DMSO). By contrast, when dissolved oxygen was present, cyclodimerization of VCZ occurred exclusively to give trans-1,2-dicarbazole-9-yl-cyclobutane in such polar, basic solvents as acetone, ethyl methyl ketone, acetonitrile or methanol. In stronger basic solvents, i.e., sulfolane, DMF, or DMSO, simultaneous radical polymerization and cyclodimerization of VCZ proceeded, the ratio of the cyclodimerization to the radical polymerization decreasing in the order, sulfolane > DMF > DMSO. In dichloromethane, on the other hand, cationic polymerization of VCZ occurred irrespective of the atmosphere. It is suggested that oxygen acts as an electron acceptor to the excited VCZ, electron transfer occurring in polar solvents from the excited VCZ to oxygen to give transient VCZ cation radical. The effect of solvent basicity on the photocyclodimerization of VCZ is discussed.