Water Solvent Method for Esterification and Amide Formation between Acid Chlorides and Alcohols Promoted by Combined Catalytic Amines: Synergy between N‐Methylimidazole and N,N,N′,N′‐Tetramethylethylenediamine (TMEDA)

An efficient method for esterification between acid chlorides and alcohols in water as solvent has been developed by combining the catalytic amines, N‐methylimidazole and N,N,N′,N′‐tetramethylethylenediamine (TMEDA). The present Schotten–Baumann‐type reaction was performed by maintaining the pH at around 11.5 using a pH controller to prevent the decomposition of acid chlorides and/or esters and to facilitate the condensation. The choice of catalysts (0.1 equiv.) was crucial: the combined use of N‐methylimidazole and TMEDA exhibited a dramatic synergistic effect. The catalytic amines have two different roles: (i) N‐methylimidazole forms highly reactive ammonium intermediates with acid chlorides and (ii) TMEDA acts as an effective HCl binder. The production of these intermediates was rationally supported by a careful ¹H NMR monitoring study. Related amide formation was also achieved between acid chlorides and primary or secondary amines, including less nucleophilic or water‐soluble amines such as 2‐(or 4‐)chloroaniline, the Weinreb N‐methoxyamine, and 2,2‐dimethoxyethanamine.     

Amines vs. N‐Oxides as Organocatalysts for Acylation,Sulfonylation and Silylation of Alcohols: 1‐Methylimidazole N‐Oxide as an Efficient Catalyst for Silylation of Tertiary Alcohols

A comparison of the relative catalytic efficiencies of Lewis‐basic amines vs. N‐oxides for the acylation, sulfonylation and silylation of primary, secondary and tertiary alcohols is reported. Whilst the amines are generally superior to the N‐oxides for acylation, the N‐oxides are superior for sulfonylation and silylation. In particular, 1‐methylimidazole N‐oxide (NMI‐O) is found to be a highly efficient catalyst for sulfonylation and silylation reactions. To the best of our knowledge, NMI‐O is the first amine or N‐oxide Lewis basic organocatalyst capable of promoting the efficient silylation of tert‐alcohols in high yield with low catalyst loading under mild reaction conditions.

     

Tertiary‐amine‐free,non‐planar,sulfone‐containing,tetrafunctional epoxy and its application as a high temperature matrix

Non‐amine‐derived tetrafunctional epoxies have several advantages over the amine‐derived N,N,N′,N′‐tetraglycidyl‐4,4′‐diaminodiphenyl methane (TGDDM) in high temperature applications. Although two non‐amine‐derived tetrafunctional epoxies were developed in our laboratory, further improvements in toughness using less loading amount is still desirable. Thus, a tertiary‐amine‐free, non‐planar and triphenylmethane‐containing tetrafunctional epoxy (STFE) with a sulfone spacer was synthesized. When it was mixed with diglycidyl ether of bisphenol A (DGEBA) and cured with 4,4′‐diaminodiphenylsulfone (DDS), both thermal and mechanical performances outperformed TGDDM. Moreover, STFE modified system shows the highest toughness (35.7 kJ m^–2) among three amine‐free and triphenylmethane‐containing epoxies at merely 5 wt% loading. Molecular simulation and thermomechanical analysis results suggest that the improved mechanical properties could be related to the geometry of the molecule and larger free volume. Despite a marginal drop in T_g, the thermal degradation temperature is better than that of TGDDM/DDS. In addition, the moisture resistance of STFE/DGEBA/DDS is much better than that of TGDDM/DDS. Thus, STFE modified DGEBA could be a potential replacement for TGDDM in some high temperature applications. © 2020 Society of Chemical Industry     

Phenyliodine Diacetate‐Mediated para‐Functionalizations of Amido‐ and Amino‐Substituted [2.2]Paracyclophanes

The reaction of N‐[2.2]paracyclophanyl‐substituted amides or amines with phenyliodine diacetate (PIDA) and protic nucleophiles affords mixed para‐substituted [2.2]paracyclophane derivatives in moderate to good yields. As protic nucleophiles carboxylic acids and alcohols as well as pyridine hydrobromide can be used. 4‐Hydroxy[2.2]paracyclophane reacts in an analogous manner.

     

Identification and Characterization of D‐Succinylase,and a Proposed Enzymatic Method for D‐Amino Acid Synthesis

Chiral amino acids are important intermediates for the pharmaceutical industry. We have developed a novel one‐pot enzymatic method for D ‐amino acid synthesis by the dynamic kinetic resolution of N‐succinyl‐dl ‐amino acids using D ‐succinylase (DSA) and N‐succinylamino acid racemase (NSAR, EC 4.2.1.113). The DSA from Cupriavidus sp. P4‐10‐C, which hydrolyzes N‐succinyl‐D ‐amino acids enantioselectively to their corresponding D ‐amino acids, was identified for the first time by screening soil microorganisms. Subsequently, the DSA gene was cloned and overexpressed in Escherichia coli. DSA was shown to comprise two subunits with molecular masses of 26 kDa and 60 kDa. Additionally, the NSAR gene from Geobacillus stearothermphilus NCA1503, which racemizes N‐succinylamino acids, was also cloned and overexpressed in E. coli. The highly purified DSA and NSAR prepared from each recombinant E. coli were characterized and used for D ‐amino acid synthesis. A one‐pot enzymatic method converted 100 mM N‐succinyl‐dl ‐phenylalanine to D ‐phenylalanine in 91.1% conversion with 86.7% ee. This novel enzymatic method may be useful for the industrial production of many D ‐amino acids.

     

Lithium Perchlorate‐Catalyzed Boc Protection of Amines and Amine Derivatives

A new mild and chemoselective method for mono‐N‐protection of amines and amine derivatives as tert‐butoxycarbonyl derivatives is reported. The reaction proceeds with lithium perchlorate (20 mol %) and pyrocarbonates, and shows general applicability. The catalytic action of LiClO₄ is specific for the activation of Boc₂O, thus acid‐sensitive functionalities of the starting materials remain unchanged in the protection process. This procedure works well for sterically hindered primary amine as well as electron‐deficient primary arylamines, primary and secondary amino alcohols, α‐amino acid esters, hydroxylamines, hydrazines and sulfonamides.     

One for Many: A Universal Reagent for Acylation Processes

This work describes acylation reactions facilitated by a type of heterocycle‐based acyl transfer agent, 2‐acyloxypyridazinone. Reactions of 2‐acyloxypyridazinone with carboxylic acids yield mixed carbonic anhydride intermediates, which are reactive and could be coupled with a wide range of substrates including acids, amines, alcohols, and thiols. The wide substrate scope, ease of operation (no additive or catalyst), storage and handling stability, and atom‐efficiency from recycling the heterocycle carrier make the reported acylating agent attractive for acylation‐based coupling reactions.

     

Effect of tertiary amines on yellowing of UV‐curable epoxide resins

The work reported demonstrates that the yellowness of UV‐curable epoxide resins can be improved by adding certain tertiary amines in appropriately determined amounts. According to the results of our experiments, 2.0 wt% benzoyl peroxide added to a resin effectively enhances the crosslinking density, and phenolic free radicals are produced during UV curing, which consequently induce yellowness via the reaction of oxygen and the free radicals. Imidazole (1‐amine) and tertiary amines, including 1,2‐dimethylimidazole (2‐amine), 2,4,6‐tris(dimethylaminomethyl)phenol (3‐amine), 1‐methylimidazole (4‐amine) and 2‐methylimidazole (5‐amine), were chosen to be added to resins, and their effects on UV conversion and yellowness were investigated. According to the experimental results, tertiary amines in the resin can provide a certain degree of improvement in yellowness index (ΔYI) and color parameter (ΔE*_ab) of the resin sample. Whatever the type of tertiary amine, it is found that the optimum content of amine in resin is 1.0 wt%. Also, among the studied amines, the 3‐amine exhibits the highest UV reactivity and the best efficiency for yellowness improvement with values of Δa*, Δb*, ΔYI and ΔE*_ab as low as ? 1.4, 6.23, 11.27 and 6.48, respectively. Copyright © 2007 Society of Chemical Industry     

Synthesis and structural characterization of novel chiral nanostructured poly(esterimide)s containing different natural amino acids and 4,4′‐thiobis(2‐tert‐butyl‐5‐methylphenol) linkages

Pyromellitic dianhydride (benzene‐1,2,4,5‐tetracarboxylic dianhydride) (1) was reacted with several amino acids in acetic acid and the resulting imide‐acid [N,N′‐(pyromellitoyl)‐bis‐L ‐amino acid diacid] (4a–4d) was obtained in high yield. The direct polycondensation reaction of these diacids with 4,4′‐thiobis(2‐tert‐butyl‐5‐methylphenol) (5) was carried out in a system of tosyl chloride(TsCl), pyridine, and N,N‐dimethyl formamide (DMF) to give a series of novel optically active poly(esterimide)s. Step‐growth polymerization was carried out by varying the time of heating and the molar ratio of TsCl/diacid, and the optimum conditions were achieved. These new chiral polymers were characterized with respect to chemical structure and purity by means of specific rotation experiments, FTIR, ¹H‐NMR, X‐ray diffraction, elemental, and thermogravimetric analysis (TGA) field emission scanning electron microscopy (FE‐SEM) techniques. These polymers are readily soluble in many polar organic solvents like DMF, N,N‐dimethyl acetamide, dimethyl sulfoxide, N‐methyl‐2‐pyrrolidone, and protic solvents such as sulfuric acid. TGA showed that the 10% weight loss temperature in a nitrogen atmosphere was more than 390°C; therefore, these new chiral polymers have useful levels of thermal stability associated with good solubility. Furthermore, study of the surface morphology of the obtained polymers by FE‐SEM showed that each polymers exhibit nanostructure morphology. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

In Situ Formed Bifunctional Primary Amine‐Imine Catalyst: Application to the Construction of Chiral Tertiary Alcohols through Asymmetric Aldol‐Type Reaction

An in situ formation method to obtain chiral bifunctional primary amine‐imine catalysts from the C₂‐symmetric chiral diimines has been developed. The efficiency of this method in the construction of chiral tertiary alcohols which are valuable pharmaceutical intermediates is proved by its application to the asymmetric aldol‐type reaction of cyclic ketones with other activated ketone compounds as the enamine acceptors, i.e., β,γ‐unsaturated α‐keto esters and isatins. In general, good to excellent diastereoselectivities and enantioselectivities (up to 96/4 dr, 96% ee for β,γ‐unsaturated α‐keto esters and up to 91/9 dr, 94% ee for isatins) were obtained. The active primary amine‐imine catalylst and enamine intermediate in the reaction process could be demonstrated by ESI‐MS analysis.     

Solid‐Phase Synthesis of 3,4‐Dihydroquinoxalin‐2(1H)‐ones via the Cyclative Cleavage of N‐Arylated Carboxamides

We describe a practical (time‐efficient, with commercially available building blocks, user friendly reaction conditions, high purity of products) synthesis of pharmacologically relevant quinoxalinones with three points of diversification that takes advantage of solid‐phase synthesis and cyclative cleavage. Resin‐bound (S)‐2‐(N‐alkyl‐2‐nitrophenyl)sulfonamide‐3‐alkyl‐N‐(2‐hydroxyethyl)propanamides, which are accessible from Fmoc‐protected α‐amino acids, 2‐nitrobenzenesulfonyl chloride and alcohols, underwent base‐mediated N‐arylation. The reduction of the nitro group produced acyclic intermediates that were subjected to acid‐mediated cyclative cleavage to yield 3,4‐dihydroquinoxalin‐2(1H)‐ones.

     

New investigation of 1‐substituted imidazole derivatives as thermal latent catalysts for epoxy‐phenolic resins

Novel 1‐substituted imidazole derivatives ( 4 – 10 ) were synthesized by imidazole and the corresponding substituted reagents (chloromethylpivalate, diphenylphosphinicchloride, di‐tert‐butyldicarbonate, 1,1′‐oxalylchloride, pyrazine, phneylisocyanat, and p‐toluensulfonylchloride). Polymerization of diglycidyl ether of bisphenol A (DGEBA) with 1‐substituted imidazole derivatives, two commercial available catalysts (imidazole and 1‐cyanoethyl‐2‐ethyl‐4‐methylimidazole) and N‐benzylpyrazinium hexafluoroantimonate were investigated as model reactions of epoxy resin systems with respect to the thermal latency and storage stability of the catalysts. The catalytic activity of 1‐substituted imidazole derivatives 4 – 10 depended on the steric and withdrawing electronic effect of the substitution groups. To characterize the cure activation energy and the viscosity‐storage time, the order of thermally latent activity is 1‐tosylimidazole ( 6 ) > 1,1′‐oxalyldiimidazole ( 8 ) > N‐benzylpyrazinium hexafluoroantimonate (BPH, 3 ) > 1‐tritylimidazole ( 9 ) > N‐phenyl‐imidazole‐1‐carboxamide ( 5 ) > 3‐(diphenylphosphinoyl)imidazole ( 7 ) > tert‐butyl‐1H‐imidazole‐1‐carboxylate ( 4 ) > 1‐cyanoethyl‐2‐ethyl‐4‐methylimidazole (2E4MZ, 2 ) > 1‐[(pivalyloxy)methyl]imidazol ( 10 ) > imidazole ( 1 ). In comparison with commercially available catalysts imidazole ( 1 ) and 1‐cyanoethyl‐2‐ethyl‐4‐methylimidazole ( 2 ) and a cationic latent catalyst N‐benzylpyrazinium hexafluoroantimonate (BPH, 3 ) as the standard compounds, in addition to 1‐[(pivalyloxy)methyl]imidazole ( 10 ), the 1‐substituted imidazole derivatives ( 4 – 9 ) revealed better thermal latency. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Preparation,characterization, and properties of crosslinked hydroxylated poly(styrene‐b‐butadiene‐b‐styrene) triblock copolymer

Acrylic acid was crosslinked with N,N′‐methylenebisacrylamide and converted to bioactive hydrogels by neutralization with different amino containing compounds. Several amino containing compounds were used such as 2‐aminopyridine, triethanol amine, hexamethylenetetramine (HMTA), pyridine, and imidazole. The best crosslinker ratio was determined in addition to the maximum absorbed water in different mediums. The antibacterial activity of the prepared gels were examined against examples of Gram‐positive (Staphylococcus aureus) and Gram‐negative bacteria (Escherichia coli) using agar plate method. The study was extended by evaluating one of prepared gels in columns as models for water filters. All prepared gels showed antibacterial action in agar plate method against both bacterium and the column method using one of the prepared gels showed excellent filtration and biocidal action. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Synthesis of N‐aryl azetidine‐2,4‐diones and polymalonamides prepared from selective ring‐opening reactions

Improved high‐yield synthesis of N‐aryl azetidine‐2,4‐dione has been achieved. The azetidine‐2,4‐dione undergoes ring‐opening reactions with aliphatic primary amines to form malonamide linkages. More importantly, this compound exhibits a high reactivity toward primary aliphatic amine group over alcohols or secondary amines. This selective end‐group functionalization is useful for preparing useful polymer intermediates. In this study polymalonamides were synthesized by fast addition reaction of aliphatic diamine and azetidine‐2,4‐dione. In the meantime, further application for structure‐controlled reaction also has been demonstrated. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3591–3599, 2007     

Sulfonic Acid‐Functionalized Ionic Liquids as Metal‐Free,Efficient and Reusable Catalysts for Direct Amination of Alcohols

A series of sulfonic acid‐functionalized (SO₃H‐functionalized) ionic liquids was synthesized and used as metal‐free, highly selective and efficient catalysts for the direct amination of alcohols. Notably, the activities of the series of SO₃H‐functionalized ionic liquids were compared and a 92% isolated yield was obtained using 3‐tetradecyl‐1‐(butyl‐4‐ sulfonyl)imidazolium trifluoromethanesulfonate ([BsTdIM][OTf]) as the catalyst. Importantly, the catalytic system has wide substrate scope including benzylic, allyl, propargylic, aliphatic alcohols with sulfonamide, amide, carbamate, aromatic amine and N‐heterocyclic compounds. Interestingly, the system was also suitable for a multi‐gram scale direct amination of alcohols. Additionally, the reusable nature of [BsTdIM][OTf] makes this protocol more attractive and avoids the disposal and neutralization of acidic catalysts. Moreover, preliminary experiments indicated that this reaction should proceed via an S_N1 pathway.     

The synthesis of symmetrical and unsymmetrical alkylaminonaphthalic‐1,8‐N‐alkylimides

Symmetrical 4‐n‐alkylamino and 2‐(n‐alkylamino)naphthalic‐1,8‐N‐alkylimides are prepared with primary amines from 4‐ and 2‐halogenonaphthalic‐1,8‐anhydrides in N‐methylpyrrolidinone. 3‐Halogenonaphthalic‐1,8‐anhydrides only react at the anhydride. Unsymmetrical 4‐compounds result by reaction of primary amines with the anhydride in ethanol and then the 4‐halogeno‐N‐alkyl product in N‐methylpyrrolidinone with primary or secondary amines © 2000 Society of Chemical Industry     

Well‐defined,environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications

In this study, both naturally occurring and artificial amino acids were successfully transformed into the corresponding urethane derivatives using diphenyl carbonate. The urethanes thus prepared could be efficiently cyclized into amino acid N‐carboxyanhydrides (NCAs) without the requirement of phosgene. In addition, the presence of primary amines converted the urethane derivatives into NCAs and initiated the ring‐opening polymerization of the in situ formed NCAs, allowing for the well‐defined synthesis of polypeptides. These polypeptides contained initiating ends functionalized by an amine‐derived residue and propagating ends bearing the reactive amino group. By precise control of the structures of the polypeptides, various polypeptide conjugates such as block copolymers and graft copolymers were successfully synthesized as designed, and their applications in antifouling coatings against proteins, drug delivery systems and biosensors were demonstrated. © 2019 Society of Chemical Industry     

The First Example of Saccharin‐Lithium Bromide Catalysis: Direct Synthesis of N‐Tosylimines from Alcohols

The first procedure to access N‐tosylimines directly from alcohols under mild and neutral conditions is reported. The protocol involves saccharin‐lithium bromide‐catalyzed oxidation of alcohols to aldehydes/ketones with chloramine‐T followed by their condensation with the in situ generated oxidation by‐product p‐toluenesulfonamide in the same reaction vessel to afford N‐tosylimines in 40–90% overall yields. The present work opens up a new and efficient synthetic route to N‐tosyimines directly from alcohols in a one‐pot procedure.     

Asymmetric Aza‐Morita–Baylis–Hillman‐Type Reactions: The Highly Enantioselective Reaction between Unmodified α,β‐ Unsaturated Aldehydes and N‐Acylimines by Organo‐co‐catalysis

The highly enantioselective organo‐co‐catalytic aza‐Morita–Baylis–Hillman (MBH)‐type reaction between N‐carbamate‐protected imines and α,β‐unsaturated aldehydes has been developed. The organic co‐catalytic system of proline and 1,4‐diazabicyclo[2.2.2]octane (DABCO) enables the asymmetric synthesis of the corresponding N‐Boc‐ and N‐Cbz‐protected β‐amino‐α‐alkylidene‐aldehydes in good to high yields and up to 99% ee. In the case of aza‐MBH‐type addition of enals to phenylprop‐2‐ene‐1‐imines, the co‐catalytic reaction exhibits excellent 1,2‐selectivity. The organo‐co‐catalytic aza‐MBH‐type reaction can also be performed by the direct highly enantioselective addition of α,β‐unsaturated aldehydes to bench‐stable N‐carbamate‐protected α‐amidosulfones to give the corresponding β‐amino‐α‐alkylidene‐aldehydes with up to 99% ee. The organo‐co‐catalytic aza‐MBH‐type reaction is also an expeditious entry to nearly enantiomerically pure β‐amino‐α‐alkylidene‐amino acids and β‐amino‐α‐alkylidene‐lactams (99% ee). The mechanism and stereochemistry of the chiral amine and DABCO co‐catalyzed aza‐MBH‐type reaction are also discussed.     

Direct synthesis of poly(4′‐oxy‐4‐biphenylcarbonyl) and poly(2‐oxy‐6‐naphthoyl) under nonstoichiometric conditions

Direct synthesis of poly(4′‐oxy‐4‐biphenylcarbonyl) (POBP) and poly(2‐oxy‐6‐naphthoyl) (PON) was examined by polycondensation of 4′‐hydroxy‐4‐biphenylcarboxylic acid (HBPA) and 2‐hydroxy‐6‐naphthoic acid (HNA) in the presence of 4‐ethoxybenzoic anhydride or 2‐naphthoic anhydride as condensation reagents. Polymerizations were carried out at 320 °C in aromatic solvents and liquid paraffin. POBP, having a number‐average degree of polymerization (DPn) of 38, was obtained as plate‐like crystals at the molar ratio of HBPA and anhydride of 50 mol%. PON was also obtained as plate‐like crystals but the DPn was only 13. HBPA and HNA were first converted to reactive acyloxyaromatic acid intermediates. Then the DPn was increased by means of reaction‐induced crystallization of oligomers and subsequent solid‐state polymerization via an acid–ester exchange under nonstoichiometric conditions caused by the monocarboxylic acid by‐product. Even though the DPn of PON was not as high, direct polycondensation of HBPA and HNA proceeded successfully with aromatic anhydrides. Copyright © 2004 Society of Chemical Industry