Temperature dependence of the reactivity of monosubstituted thiophenols by applying the hydrogen-isotope exchange reaction in a liquid-solid system

In order to reveal the reactivity of monosubstituted thiophenols, the hydrogen-isotope exchange reaction between T-labeled poly(vinyl alcohol) and each monosubstituted thiophenol (unlabeled) was studied in a liquid-solid system. Using both the data obtained and theA-McKay plot method, the reaction was analyzed, and the rate constant (k) for the monosubstituted thiophenol has been obtained. Consequently, it has been found that (1) the higher the temperature is, the larger is the reactivity of monosubstituted thiophenols, (2) the temperature dependence of the effect of the substituent (in a monosubstituted thiophenol) on the reactivity of the monosubstituted thiophenol is weak, (3) the reactivity of monosubstituted thiophenols follows the Hammett rule, (4) the reactivity of monosubstituted thiophenols can be enhanced with one of the electron-attractive substituents.     

Thermospray liquid chromatography/mass spectrometry of quaternary ammonium saltst

Various esters of choline and carnitine have been shown to undergo fragmentation dependent on both the structures of the molecules and the vapor and block temperatures when subjected to thermospray ionization mass spectrometry. The fragments observed vary with the structure of the ester portion and the backbone of the molecules, and are consistent with the compounds undergoing three types of reactions: (1) carbon—nitrogen bond cleavage to tertiary amines and alkyl compounds, (2) hydrolysis of the ester linkage, forming alcohols and organic acids, and (3) deacylation of the molecules to form acids and the corresponding quaternary alkene. The general applicability of the carbon—nitrogen bond cleavage mechanism was studied with other classes of quaternary compounds, but the sole products consistently detected for pyridinium, benzyldimethyldodecylammonium and tetraalkylammonium salts were amines. The fragments observed for the esters of choline and carnitine and also the anticholinergic 2,2-diphenyl-4-diisopropylaminobutyramide methiodide suggest that the mechanism of the thermospray fragmentation pathway is similar to that of the Hofmann elimination reaction.     

Catalytic hydrolysis of α-amino esters in the presence of chiral palladacycles

The rate of hydrolysis of esters derived from optically active α-amino acids, catalyzed by chiral cyclopalladated benzylamines, depends on the configuration of chiral centers in the substrate and catalyst. The catalytic hydrolysis of sulfur-containing amino esters follows an intramolecular mechanism, and the difference in the reaction rates for the stereoisomers increases in going from ortho-palladated primary benzylamines (k _S/k _R = 1.1) to tertiary amines (k _S/k _R = 1.5); the strongest catalytic effect is observed for an ester and a complex with the same absolute configuration of the chiral centers. The efficiency of intermolecular catalysis is greater for a complex and ester with opposite absolute configurations of the chiral centers, and the rate constants of catalytic hydrolysis for two pairs of stereoisomers coincide within experimental error. The maximal difference in the reaction rates is observed for cyclopalladated secondary benzylamines; it reaches 2.3 for the phenylalanine ester.     

ELECTROPHILIC CLEAVAGE OF SULFENATE ESTERS. I. POSSIBLE BIOLOGICAL IMPLICATIONS

Abstract

Base-assisted electrophilic cleavage of sulfenate esters was studied with reference to possible biological models. It is suggested that sulfenate esters (RSOR') may serve as intermediates in oxidations involving alcohol dehydrogenases. Models for the biological oxidation of alcohols via sulfenate ester intermediates are presented. The lipoic acid catalyzed dehydrogenation step in the actions of α-ketoacid oxidases (e.g., pyruvic acid dehydrogenase and α-keto glutarate dehydrogenase) is also explained in terms of a possible sulfenate ester intermediate.

In the interaction of alcohols and amines, with membrane proteins, the possibility of reversible formation of sulfenate esters and of sulfenamide formation is suggested. Experimental support is given for the formation of carbonyl compounds, from alcohols via sulfenate esters and subsequent electrophilic attack by N-iodosuccinimide on the esters. Such reactions of sulfenyl esters open virtually unexplored areas of chemistry and of the related biological implications. Methyl fluorosulfate (‘magic methyl’) in presence of base is also effective for the cleavage reaction.     

Kinetics and mechanism of the hydrolysis of esters of hydroxymethylphosphonic and hydroxymethylethylphosphinic acids

Conclusions The reactivity of ethyl esters of phosphonic and phosphinic acids containing a hydroxymethyl group at the phosphorus atom in their reaction with hydroxide anion is usually high as a consequence of intramolecular catalysis of the cleavage of the ester bond involving the ionized OH group. The spontaneous hydrolysis of these esters proceeds according to a mechanism analogous to that for other alkyl esters of tetracoordinated phosphorus acids.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2139–2140, September, 1985.     

Aqueous solutions of geminal alkylammonium surfactants as a medium for reactions of long-chain amines

The formation of surfactant-hydrophobic amine mixed aggregates reduces the pK _a of long-chain amines by 1–1.5 units compared with those in molecular solutions and is an important factor responsible for the high catalytic effect of the system in ester bond cleavage. In aqueous solution of geminal surfactants, the rate of azomethine formation in the reaction of long-chain amines with benzaldehydes is an order-of-magnitude higher than in ethanol.     

Studies on the enzymatic hydrolysis of polyesters I. Low molecular mass model esters and aliphatic polyesters

The bio-catalysed cleavage of ester bonds in low molecular mass model esters and aliphatic polyesters was studied in detail with the aim to gain improved information about the underlying mechanism and the parameters controlling polyester degradation. Among various hydrolytic enzymes the lipase of Pseudomonas species (PsL) was chosen for the investigations. In the heterogeneous phase system the specific hydrolysis rate of the esters was constant as long as free substrate surface was available. In addition to aliphatic low molecular mass model esters, also cycloaliphatic and aromatic esters were cleaved by PsL, indicating that a steric hindrance of the enzymatic ester cleavage is not the predominant controlling factor in polyester degradation. However, the cleavage rates of the aliphatic model esters are larger by more than an order of magnitude. For aliphatic polyesters the temperature difference between the melting point of the polymer and the temperature where degradation takes place (ΔT_mt), turned out to be the primary controlling parameter for polyester degradation with the lipase. Only if ΔT_mt<30 °C, a measurable enzymatic degradation rate is found. ΔT_mt can be regarded as a measure of the mobility of the polyesters chains in the crystalline domains, necessary for the access of the esters to the active site of the lipase. Though aliphatic homopolyesters are seemingly very similar with regard to their chemical structure and reactivity of the ester bonds, their enzymatic degradation rates still differ significantly even at the same ΔT_mt. These differences have obviously to be attributed to small changes in the chemical structure, as, for instance, the C number of the aliphatic diacid.     

An enzyme-labile safety catch linker for synthesis on a soluble polymeric support

The development of new and broadly applicable linker groups which are stable under a variety of reaction conditions and allow release of the desired products from the solid support under very mild conditions is of great interest in organic synthesis and combinatorial chemistry. We describe an enzyme-labile safety-catch linker which releases alcohols and amines through i) enzymatic cleavage of an amino group and ii) subsequent lactam formation. The linker group was investigated on different polymeric supports: TentaGel. PEGA, CPG-beads and the soluble polymer POE-6000. From these linker-polymer conjugates 2-methoxy-5-nitrobenzyl alcohol was released by penicillin G acylase catalysed cleavage of a phenylacetamide and attack of the liberated benzylamine on the neighbouring ester group in ortho position. The model study revealed that only in the case of soluble POE-6000 conjugate high yields for the cleavage could be achieved. In the case of the other solid supports the enzyme does not have access to the interior of the polymer matrix. The application of the POE-6000 linker conjugate was investigated for various esters in Pd0-catalysed Heck-, Suzuki- and Sonogashira reactions as well as in a Mitsunobu reaction and cycloadditions. These studies proved that the linker is stable under a broad variety of reaction conditions and that the enzymatic method allows for release of the desired product alcohols under extremely mild conditions at pH 7 and 37 degrees C. In addition, the enzymatic reaction proceeds with complete chemoselectivity, that is other esters or amides are not attacked by the biocatalyst. In addition to alcohols amines can also be cleaved by means of the enzyme-initiated two-step process. In these cases the higher stability of amides as compared to esters requires warming to 60 degrees C to induce cyclization and release of the desired product.     

Aromatic Ring Strain in Arylselenenyl Bromides: Role in Facile Synthesis of Selenenate Esters via Intramolecular Cyclization

The synthesis and reactivity of 2,6‐disubstituted arylselenium compounds derived from 2‐bromo‐5‐tert‐butylisophthalic acid ( 43 ) are described. The syntheses of bis(5‐tert‐butylisophthalic acid dimethyl ester)diselenide ( 46 ) and bis(5‐tert‐butylisophthalic acid diisopropyl ester)diselenide ( 47 ) have been achieved by the reaction of the corresponding ester precursors with disodium diselenide. Reduction of diselenide 46 with lithium aluminum hydride affords 2,2′‐bis(5‐tert‐butylbenzene‐1,3‐dimethanol)diselenide ( 53 ). Diselenides 46 and 47 exhibit intramolecular Se???O interaction. Compound 53 does not show any intramolecular Se???O interaction. The anomalous Se???O nonbonded coordination observed in the single‐crystal X‐ray structures of compounds 46 , 47 and 53 is compared and contrasted. The corresponding selenenyl bromides 54 and 55 , derived from the reaction of diselenides 46 and 47 with bromine, are quite stable in the solid state. However, they undergo hydrolysis and subsequent intramolecular cyclization upon heating or after having been kept in solution over a period of time to give the corresponding selenenate esters 56 and 57 . The X‐ray crystallographic study and density functional theory calculations on 54 at the B3LYP/6‐31G(d) level of theory indicate a significant distortion in planarity of the aromatic ring. Glutathione peroxidase‐like activities of diselenides 46 and 47 and their selenenate esters 56 and 57 have been studied both by thiophenol and bioassay methods. The very low glutathione peroxidase‐like activity of the diselenides ( 46 and 47 ) and their selenenate esters ( 56 and 57 ) in the thiophenol assay is attributed to the presence of the relatively strong Se???O intramolecular interaction in the selenenyl sulfide intermediates. The interaction retards the catalytic activity through both thiol exchange and an intramolecular cyclization reaction.     

有机磷化合物的研究 X:五价膦(磷)酸酯与卤代烷在卤化钠存在下的酯烷基交换反应

A detailed study on the ester alkyl exchange reaction of various types of quinique-valent phosphorus esters with alkyl halide in the presence of sodium bromides was reported. This ester alkyl exchange reaction was evidently influenced by the structure of phosphorus esters and alkyl halides as well as by the nature of the halides of metal ions. In contrast with the reaction without sodium hadlide, the alkyl phosphinmate is more reactive than phosphonate and phosphate by treatment with alkyl halide in the presence of sodium halide. This is consistent with the high nucleophilicity of >P(CO)O- as leaving group. The reactivity of butyl halides was decreased in the following order: n-BuBr>i-BuBr=s-BuBr>t-BuBr. Alkyl iodide was proved to be more reactive than the corresponding bromide and chloride. However, the use of iodioe is limited by the formation of alkene resulted from the elimination of HI. These structural effects show the general characteristics of a nucleophilic substitution reaction. A reaction mechanism involving the formation of sodium salt intermecutiate was proposed based on the concept of HSAB principle. This reaction may, however, be used as a convenient method for the preparation of mixed esters of quinque-valent phosphorus acids.     

Addition reactions of pendant epoxide group in poly(glycidyl methacrylate) with various active esters

Addition reactions of pendant epoxide groups in poly(glycidyl methacrylate) (PGMA) with various active esters such as 1-benzotriazolyl benzoate, S-(2-benzoxazolyl) thiobenzoate, S-(2-benzothiazolyl) thiobenzoate, 4-nitrophenyl benzoate (4NPB), and S-phenyl thiobenzoate (PTB) were carried out using quaternary salts as catalysts. The reactions of PGMA with those active esters proceeded in diglyme at 100°C for 24 h quantitatively without the formation of 2-hydroxyl pendant groups in the polymer when 10 mol % of tetraethylammonium bromide was used as a catalyst. Furthermore, it was found that the respective quaternary salts have higher catalytic activity than tertiary amines in the reaction of PGMA with the active esters, and the reaction of PGMA with 4NPB gave the corresponding polymer with the highest conversion by addition of tetrabutylammonium bromide as a catalyst, while tetraethylammonium chloride showed the highest activity for the reaction of PGMA with PTB. In addition, the rate of reaction of PGMA with 4NPB was proportional to third order kinetics of the epoxide concentration, the ester concentration and the catalyst concentration as follows: ?d[Epoxide]/dt = ?[Ester]/dt = k₃[Epoxide] [Ester] [Catalyst].     

Synthesis and thermal self-crosslinking reaction of polymer containing spiro ortho ester and carboxylic acid

Polymers with both pendant spiro ortho ester and carboxylic acid moieties were synthesized by partial esterification of poly(methacrylic acid), poly(methacrylic acid-co-methyl methacrylate), or poly(methacrylic acid-co-styrene) with halomethylated spiro ortho esters in the presence of 1,8-diazabicyclo[5,4,0]undecene-7 in dimethyl sulfoxide. The extent of esterification increased with increasing reaction temperature. The reaction of polymeric carboxylic acids with chloromethylated spiro ortho esters proceeded to 80% of conversion at 100°C for 120 h. In contrast, the degree of esterification with bromomethylated spiro ortho ester reached 80% at 60°C within 24 h. Thermo-crosslinking of polymers having pendant spiro ortho ester moiety and carboxylic acid could be effected in films. The rate of spiro ortho ester ring-opening increased with increasing reaction temperature and with increasing content of carboxylic acid groups in the polymer. Further, the rates of gel production were also measured. The polymer containing an equimolar mixture of spiro ortho ester moieties and carboxylic acids exhibited the highest reactivity. In addition, it was found that thermal crosslinking reaction of the polymer occurred with minimum volume shrinkage.     

N-烷基-N-酰基磺酰胺聚苯乙烯基微球作为固相酰化剂的研究

一种可循环使用的固相试剂：N-烷基-N-酰基磺酰胺聚苯乙烯基微球(5), 通过对聚苯乙烯磺酰氯微球树脂进行两步功能基化的修饰反应来制备. 制备过程如下：聚苯磺酰氯树脂(1)与伯胺(2)反应得到聚苯乙烯基N-烷基磺酰胺树脂(3), 树脂3用酰氯(4)或酸酐酰化得到N-烷基-N-酰基磺酰胺聚苯乙烯基树脂(5). 酰化的树脂5作为酰基转移试剂与亲核试剂胺反应得到二级酰胺. 根据5上取代基对酰胺生成的程度的影响结果表明, 烷基R¹和酰基(R²CO)对酰基转移反应活性的大小依次分别为：苯基＞苄基＞甲基＞正丁基＞＞H和对硝基苯甲酰基(苯甲酰基＞乙酰基. 胺的亲核能力对酰胺的收率也有一定的影响. N-苯基-N-苯甲酰基磺酰胺树脂重复使用3次没有发现活性降低.     

A Garratt-Braverman route to isoindolines and phthalans

Garratt-Braverman (GB) cyclization, two CC bond forming reaction in a single step, has been utilized to construct several isoindoline and phthalan derivatives. The precursors were the bispropargyl protected amines and ethers with one of the propargyl arm substituted with an alkene moiety. The GB cyclizations were generally carried out in presence of DBU in refluxing toluene. In case of the bispropargyl amine systems with the alkene arm substituted with electron withdrawing ester group, the cyclization occurred at room temperature. The yields of cyclization ranged from 64 to 86% which are acceptable considering the formation of two CC bonds. The protected isoindolines could be successfully deprotected by treatment with thiophenol in presence of triethyl amine and the corresponding free amines were isolated as the TFA salts.     

Solid-phase synthesis of 1,2,3,4-tetrahydroisoquinoline derivatives employing support-bound tyrosine esters in the Pictet-Spengler reaction

The solid-phase synthesis of 1,2,3,4-tetrahydroisoquinoline-3-carboxamides employing carboxyl-supported, o-alkylated tyrosine esters in a Pictet-Spengler reaction is described. Esterification of [4-(hydroxyphenyl)thiomethyl]polystyrene (Marshall resin) with ethers of N-BOC-L-tyrosine using diisopropylcarbodiimide (DIC) and 4-dimethylaminopyridine (4-DMAP) afforded the solid-supported ester derivatives. Removal of the BOC group with trifluoroacetic acid (TFA) afforded the carboxyl-supported tyrosine ester, which was then treated with paraformaldehyde and TFA to afford the desired solid-supported counterpart. Acylation of the secondary amine with arylsulfonyl chlorides followed by reaction with amines resulted in the formation of the desired 2-arylsulfonyl-7-alkoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamides. Alternatively, the support-bound tetrahydroisoquinoline-3-carboxylate derivatives could be treated with an aldehyde and a reducing agent to give the corresponding support-bound tertiary amine. Exposure of these resin-bound products to amines afforded the corresponding 2-alkyl-7-alkoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamides after cleavage from the resin. Alternative routes to the desired chemotypes, as well optimization of the conditions for the Pictet-Spengler reaction and the conditions for the acylation and reductive amination of the support-bound secondary amines, are also described.     

An efficient and practical chemoenzymatic preparation of optically active secondary amines

[reaction: see text] An efficient and practical chemoenzymatic method was developed for the preparation of a variety of chiral secondary amines. Here, oxalamic esters were identified as unique derivatives amenable to the enzyme-catalyzed kinetic resolution of racemic secondary amines. Both enantiomers of the amines were produced in high optical purity and yields after the cleavage of the oxalamic groups.     

Lipase-Catalyzed Synthesis of Carboxylic Amides: Nitrogen Nucleophiles as Acyl Acceptor

 The lipase-catalyzed aminolysis of carboxylic esters is a fairly general reaction that has been performed with a wide range of esters and amines, generally in anhydrous organic media to avoid undesirable hydrolysis of the ester. Alternatively, carboxylic amides can be synthesized by lipase mediated condensation of carboxylic acids and amines if an excess of either reactant is avoided. Chiral carboxylic esters have been resolved by lipase-catalyzed aminolysis. In the majority of these resolutions, Candida antarctica lipase B has been employed as the catalyst. A range of chiral amines has been resolved by lipase mediated acylation, using mainly the lipases from C. antarctica (B type) and Pseudomonas species. The enantiorecognition was frequently found to depend critically on the acylating agent and the reaction medium.     

LiClO4-Accelerated Three-Component Mannich-Type Reaction of Diethyl Malonate with Imines: An Efficient Synthesis of β-Amino Esters Under Solvent-Free Conditions

LiClO₄ is used as catalyst for direct Mannich-type reaction of aryl aldehydes, aryl amines, and diethyl malonic ester under solvent-free conditions. This three-component reaction afforded the corresponding β-amino esters in good yields with simple and environmentally benign procedure.     

Mild amidation of aldehydes with amines mediated by lanthanide catalysts

Catalytic amidation of aldehydes with amines is efficiently mediated by homoleptic lanthanide amido complexes, Ln[N(SiMe3)2]3 (Ln = La, Sm, and Y). Amidation reactivity follows the trend: La > Sm approximately Y. These reactions proceed in high yield without added oxidants, bases, and/or heat or light, which are usually required in other catalytic amidation processes. The reaction is demonstrated with a variety of amines, with yields as high as 98% based on amine.     

Lipase-Catalyzed Synthesis of Carboxylic Amides: Nitrogen Nucleophiles as Acyl Acceptor

Summary.  The lipase-catalyzed aminolysis of carboxylic esters is a fairly general reaction that has been performed with a wide range of esters and amines, generally in anhydrous organic media to avoid undesirable hydrolysis of the ester. Alternatively, carboxylic amides can be synthesized by lipase mediated condensation of carboxylic acids and amines if an excess of either reactant is avoided. Chiral carboxylic esters have been resolved by lipase-catalyzed aminolysis. In the majority of these resolutions, Candida antarctica lipase B has been employed as the catalyst. A range of chiral amines has been resolved by lipase mediated acylation, using mainly the lipases from C. antarctica (B type) and Pseudomonas species. The enantiorecognition was frequently found to depend critically on the acylating agent and the reaction medium. Received December 20, 1999. Accepted January 1, 2000