N-Butyl-2,4-dinitro-anilinium p-toluenesulfonate as a highly active and selective esterification catalyst

N-Butyl-2,4-dinitro-anilinium p-toluenesulfonate (1) was found to be a very active esterification catalyst that promotes condensation of equal mole amount of carboxylic acids and alcohols under mild conditions. This catalyst is also highly selective towards carboxylic acid and alcohol substrates at ambient temperature.     

Bulky diarylammonium arenesulfonates as mild and extremely active dehydrative ester condensation catalysts

More environmentally benign alternatives to current chemical processes, especially large-scale, fundamental reactions like ester condensations, are highly desirable for many reactions. Bulky diarylammonium pentafluorobenzenesulfonates and tosylates serve as extremely active dehydration catalysts for the ester condensation reaction of carboxylic acids with equimolar amounts of sterically demanding alcohols and acid-sensitive alcohols. Typically, the esterification reaction is performed in heptane by heating at 80 °C in the presence of 1 mol% of the catalyst without removing water. Esterification with primary alcohols proceeds without solvents even at room temperature. Furthermore, 4-(N-mesitylamino)polystyrene resin-bound pentafluorobenzenesulfonate can be recycled more than 10 times without a loss of activity.     

Effect of structure of the amino acids and amines on the rate and mechanism of their condensations with pyridoxal

Kinetics and mechanism of condensation of amino acids and amines of different structure and their derivatives with pyridoxal were studied. It was established that the amino acid with secondary amino group, proline, adds to pyridoxal with the formation of amino alcohol. α-Amino acids in the course of condensation with pyridoxal form amino alcohols which transform to Schiff bases. The latter compounds by elimination of the α-hydrogen atom or CO₂ from the amino acid fragment and the subsequent hydrolysis of the quinoid structure form the final products. β- And ɛ-amino acids react with pyridoxal to form Schiff bases which are stable to chemical transformations. The possibility was shown of their conversion to the quinoid structure. It was established that the guanidine structure of the molecule of L-arginine unlike its α-NH₂ group did not take part in the condensation with pyridoxal. The quantitative evaluation of the condensation rates of triptamine, Ltriptofane, and its methyl ester in the stage of dehydration of their amino alcohols was carried out.     

New boron(III)-catalyzed amide and ester condensation reactions

In 1996, we reported that benzeneboronic acids bearing electron-withdrawing groups at the meta- or para-position are highly effective catalysts for the amide condensation reaction in less-polar solvents. In this paper, we report that N-alkyl-4-boronopyridinium halides are more effective catalysts than the previous ones in more polar solvents. N-Alkyl-4-boronopyridinium halides are effective not only for amide condensation between equimolar mixtures of carboxylic acids and amines but also for the esterification of α-hydroxycarboxylic acids in alcohol solvents. Furthermore, perchlorocatecholborane is more effective than areneboronic acids for the amide condensation of sterically demanding carboxylic acids. In addition, Lewis acid-assisted Brønsted acid (LBA), which is prepared from a 1:2 M mixture of boric acid and tetrachlorocatechol, is effective for the Ritter reaction from alcohols and nitriles to amides.     

A simple synthesis and purification of 1-ferrocenylalkyl alcohols

An alternative method for the preparation of 1-ferrocenylalkyl alcohols has been developed. This involves condensation of ferrocene with carbonyl compounds in concentrated sulfuric acid and addition of the resulting solutions of 1-ferrocenylalkylium ions into aqueous sodium bicarbonate. The mixtures are then treated with thioglycolic acid and the S-(1-ferrocenylalkyl)thioglycolic acids purified via sodium salts and hydrolysed in the presence of copper powder to give 1-ferrocenylalkyl alcohols in good yields.     

Efficient condensation of carboxylic acids with alcohols catalyzed by fluorous ammonium triflates

The use of fluorous ammonium salts as metal-free catalysts for the direct condensation of equimolar amounts of carboxylic acids and aliphatic alcohols has been investigated. Esterification reactions were thus conveniently carried out under mild fluorous biphasic conditions, in the presence of 1 mol % of fluorous ammonium triflate and without recourse to any additional water removal technique. Good to excellent ester yields were obtained in the case of primary and secondary aliphatic alcohols. The fluorous salt was easily recovered by simple phase separation and reused at least three times without considerable loss of activity.     

General Method to Increase Carboxylic Acid Content on Nanodiamonds

Carboxylic acid is a commonly utilized functional group for covalent surface conjugation of carbon nanoparticles that is typically generated by acid oxidation. However, acid oxidation generates additional oxygen containing groups, including epoxides, ketones, aldehydes, lactones, and alcohols. We present a method to specifically enrich the carboxylic acid content on fluorescent nanodiamond (FND) surfaces. Lithium aluminum hydride is used to reduce oxygen containing surface groups to alcohols. The alcohols are then converted to carboxylic acids through a rhodium (II) acetate catalyzed carbene insertion reaction with tert–butyl diazoacetate and subsequent ester cleavage with trifluoroacetic acid. This carboxylic acid enrichment process significantly enhanced nanodiamond homogeneity and improved the efficiency of functionalizing the FND surface. Biotin functionalized fluorescent nanodiamonds were demonstrated to be robust and stable single-molecule fluorescence and optical trapping probes.     

Widely useful DMAP-catalyzed esterification under auxiliary base- and solvent-free conditions

With regard to atom economy and E-factor, catalytic condensation of carboxylic acids with equimolar amounts of alcohols is the most desirable. Although several highly active dehydration catalysts have been reported, more efficient alternatives are still strongly needed because the dehydrative esterification of tertiary alcohols, phenols, acid-sensitive alcohols, amino acids, and hardly soluble alcohols has never proceeded satisfactorily. Here we report new insights into the classical DMAP-catalyzed acylation of alcohols: surprisingly, only a 0.05-2 mol % of DMAP can efficiently promote acylation of alcohols with acid anhydrides under auxiliary base- and solvent-free conditions to give the corresponding esters in high yields. Furthermore, we achieved the recovery and reuse of commercially available polystyrene-supported DMAP without using any solvents. These serendipitous findings provide widely useful and environmentally benign esterification methods, which might be more practical and reliable than catalytic dehydrative condensation methods, in particular, for the less reactive alcohols which hardly condense with carboxylic acid directly.     

An improved Pfitzinger reaction for the direct synthesis of quinoline-4-carboxylic esters/acids mediated by TMSCl

An efficient and facile synthesis of quinoline-4-carboxylic esters/acids by TMSCl-promoted reaction of easily available N,N-dimethylenaminones and isatins in alcohols/water has been developed. The improved Pfitzinger reaction involves esterification and cyclization in one-step process, and in situ formed a carboxylic ester/acid group (CO₂R or COOH) at the 4-position of quinoline ring. Moreover, the key features of this protocol are readily available starting materials, good functional group tolerance, mild reaction conditions, operational simplicity, and feasibility of scale up.     

Kinetics and mechanism of the condensation of pyridoxal hydrochloride with L-tryptophan and D-tryptophan,and the chemical transformation of their products

The kinetics and mechanism of interaction between pyridoxal and L-tryptophan, D-tryptophan, and their derivatives are studied. It is found that condensation reactions proceed via three kinetically distinguishable stages: (1) the rapid intraplanar addition of the NH₂ groups of the amino acids to pyridoxal with the formation of amino alcohols; (2) the rotational isomerism of amino alcohol fragments with their subsequent dehydration and the formation of a Schiff base with a specific configuration; (3) the abstraction of α-hydrogen in the product of condensation of pyridoxal with L-tryptophan, or the abstraction of СО₂ in the product of condensation of pyridoxal with D-tryptophan with the formation of quinoid structures, hydrolysis of which results in the preparation of pyridoxamine and keto acid or pyridoxal and tryptamine, respectively. Schiff bases resistant to further chemical transformations are formed in the reaction with tryptophan methyl ester.     

Bulky diarylammonium arenesulfonates as selective esterification catalysts

More environmentally benign alternatives to current chemical processes, especially large-scale, fundamental reactions such as ester condensations, are highly desirable for many reactions. Bulky diarylammonium pentafluorobenzenesulfonates and tosylates serve as extremely active dehydration catalysts for the ester condensation reaction of carboxylic acids with equimolar amounts of sterically demanding alcohols and acid-sensitive alcohols. Typically, the esterification reaction is performed in heptane by heating at 80 degrees C in the presence of 1 mol % of the catalyst without removing water. Esterification with primary alcohols proceeds without solvents even at room temperature. Furthermore, 4-(N-mesitylamino)polystyrene resin-bound pentafluorobenzenesulfonate can be recycled more than 10 times without activity loss.     

炔酰胺类缩合剂研究进展

缩合剂是指用于促成羧酸与胺或者醇直接缩合构建酰胺键或酯键的一类试剂的总称.由于酰胺和酯的重要性,缩合剂的开发成为了学术界与工业界广泛关注的一个重要研究方向.多肽合成就是α-氨基酸在缩合剂的作用下反复形成酰胺键的过程,因此,缩合剂在多肽合成中发挥着至关重要的作用.当前多肽合成所使用的试剂和技术大多是20世纪50~80年代发展起来的,这些试剂和技术的天生弊端逐渐显现出来.比如传统多肽缩合剂过度活化α-氨基酸而诱发的外消旋化和其它副反应导致的副产物成为药物多肽生产过程中一个极为关切的问题.另外固相多肽合成的低原子经济性给可持续发展带来了极大的挑战.这些问题只能依靠原始创新的颠覆性技术和全新的缩合方法来解决.我们课题组致力于通过发展新试剂和新反应来解决多肽与蛋白质化学合成领域的难题.本文系统介绍了我们发展的一种结构全新的炔酰胺类缩合试剂及其在酰胺、酯、大环内酯、多肽、硫代多肽合成中的应用研究进展.     

Reactions of aldehydes of the furan series

The lability of the hydrogen atoms in the methyl group of 5-methylfurfural was proved by a reaction of the crotonic condensation type. Aldehydes, alcohols, and acids of the 1,2-di(2-furyl)ethylene series were synthesized. The optimum conditions (reagent ratio, elevated temperatures, catalysis by sodium ethoxide) that make it possible for the condensation process to prevail over side reactions were selected. The Cannizzarro reaction that accompanies condensation is the reason for the accumulation in the reaction mixture of furfuryl alcohols and furancarboxylic acids. Aldehydes of the 1,2-di-(2-furyl)ethylene series also participate in this reaction, on the basis of which it is proposed that alcohols and acids of this series be obtained by this method.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No, 9, pp. 1168–1171, September, 1977.We thank Professor V. G. Kul'nevich for his valuable instructions with respect to this research.     

Enzymatic kinetic resolution of ketorolac

Ketorolac 1 was resolved into each enantiomer by interesterification using lipase B from Candida antarctica. The acid reacted with various alcohols and the ester and acid were resolved up to >99% e.e. when reacted with octanol, which was the best result. To increase reactivity and enantioselectivity, the experimental conditions were adjusted by varying temperature, solvent, alcohols and reaction time.     

Condensation of 1-alkoxy-1,3-butadienes with optically active glyoxylic acid esters

The condensation of 1-alkoxy-1,3-butadienes with optically active esters of glyoxylic acid leading to esters of 2-alkoxy-5,6-dihydro-2H-pyran-6-carboxylic acids was studied and the dependence of asymmetric induction on the following parameters examined: alkoxy group in dienes, dissymetric group in glyoxylates, solvent and the temperature of condensation. The optical yield and absolute configuration of the adducts were determined by optical rotation measurements of methyl malate obtained by degradation. The data are rationalized by postulating parallel formation of four active complexes corresponding to a transoid and cisoid conformation of the glyoxylate ester in the transition state.     

Stereoselective Synthesis of γ-hydroxy-α-amino acids via intramolecular amidomercuration

A general method for the stereoselective conversion of homoallylic alcohols to erythro- or threo-β-hydroxy-α-amino acids is described. The key step is the stereoselective mercuric ion-initiated cyclofunctionalization of acylaminomethyl ether derivatives of the homoallylic alcohols (3 → 8). The stereochemistry of the products obtained from the cyclofunctionalization is controlled by the choice of reaction conditions. Reaction under conditions of kinetic control leads to predominant formation of cis 4,6-disubstituted tetrahydro-1,3-oxazines, while reaction under conditions which allow for equilibration of the organomercurial intermediates results in the formation of the trans stereoisomer with very high stereoselectivity. Oxidative demercuration and oxidation of the resulting alcohol produces a protected form of the title amino acids (8 → 9 → 10). Cleavage of the tetrahydrooxazine ring with hydrobromic acid then produces the amino acid products asγ-butyrolactone hydrobromides (11 and 12). This general method thus allows for stereoselective synthesis of either diastereomer of the amino acid product starting with a single homoallylic alcohol.     

An efficient access to (Z)-β-fluoroallyl alcohols based on the two carbon homologation of aromatic aldehydes by Horner–Wadsworth–Emmons reaction with 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid,S-ethyl ester followed by reduction with sodium borohydride

We describe a biomimetic approach to (Z)-β-fluoroallyl alcohols based on the two carbon homologation of aromatic aldehydes to α-fluorocinnamic thioesters by Horner–Wadsworth–Emmons reaction with 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl ester, followed by reduction with sodium borohydride in mild conditions. The α-fluorothioesters were obtained in a good yield by condensing the aldehydes with the lithium anion of 2-(diethoxyphosphinyl)-2-fluoro-ethanethioic acid, S-ethyl ester in THF at ?78 °C. The (E,Z)-α-fluorocinnamic thioester mixtures were then cleanly reduced with double bond isomerisation to the corresponding (Z)-β-fluoroallyl alcohols by NaBH₄ at room temperature. This methodology may be applied to highly functionalized aldehydes as exemplified by the straightforward access to (Z)-β-fluoroconiferin, a strong inhibitor of lignin polymerization from O-glucosylated vanillin.     

Stereoselective synthesis of highly enantioenriched 3-methyl-2-cyclohexen-1-ones possessing an asymmetric quaternary carbon as C-4 or C-6: a sugar template approach

The 1,4-addition of the enolate generated from α-methylated acetoacetate incorporated at C-4 of methyl 6-deoxy-2,3-di-O-(tert-butyldimethylsilyl)-α-d-glucopyranoside to methyl vinyl ketone, followed by aldol condensation of the resulting 1,4-addition product under two base-mediated conditions, provided 4-O-functionalized d-glucose derivatives with high diastereoselectivity. These products install a 3-methyl-2-cyclohexen-1-one-4- (or -6-) carboxylic acid as the O-4 ester, in which C-4 or C-6 is an asymmetric quaternary carbon. Removal of the sugar template from those aldol condensation products provided synthetically useful 3,6-dimethyl-2-cyclohexen-1-one-6-carboxylic acid and 3,4-dimethyl-2-cyclohexen-1-one-4-carboxylic acid derivatives both in high enantioenriched forms.     

Synthesis of esters of o-dicarboxylic acids of the quinoxaline series

Esters of substituted quinoxaline-2,3-dicarboxylic acids (Table 1), which are intermediates in the synthesis of heterocyclic analogs of phthalocyanin [2,3], were synthesized by the condensation of aromatic o-diamines with esters of diketosuccinic acid [1]. A similar condensation is described only in the case of a heterocyclic o-diamine — 2,3-diaminoquinoxaline [4], 2,3-Dihydroxyquinoxaline was isolated instead of the expected ester of quinoxalinedicarboxylic acid in [5] by the reaction of o-phenylenediamine with diethyl diketosuccinate; however, we were able to obtain the normal condensation products by using pure starting ester.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 280–281, February, 1971.     

HPLC of fatty acid esters of mono- and polyhydric alcohols. Part 2: Preparative separation

This paper demonstrates how simply and rapidly fatty acid esters of mono- and polyhydric alcohols can be separated quantitatively in preparative quantities on Lobar® RP-8 packed columns. After the separation of unknown mixtures, the isolated esters are identified from spectroscopic data (IR/NMR) and, after saponification of the ester components (fatty acids and alcohols), from the retention times of gas and high-pressure liquid chromatographic separations. Thus, in particular, sparingly volatile or nonvolatile partial esters of polyhydric alcohols, as well as the long-chained full esters, can be determined qualitatively and quantitatively. The following fatty acid esters of mono- and polyhydric alcohols have been separated: the i-propylesters of the laurinic and myristinic acids, the i-butyl-, i-octyl- and i-octadecyl-esters of the palmitinic and stearic acids, the mono- and di-fatty acid esters of the 1,3-bis-(2-hydroxyethyl)-5,5-dimethylhydantoins, the mono-, di- and tri-esters of the trimethylalpropane and the full esters of the pentaerythrite.