Synthesis of L-Lysine and L-Glutamic Acid Derivatives with Long Alkyl Chains and Polycondensation of Langmuir-Blodgett Films

Two esters of L-lysine and L-glutamic acid containing long alkyl groups were synthesized and their polycondensation in monolayers and multilayers was investigated. The pressure-area isotherms of the ester of L-lysine depend markedly on the time of residence at the air-water interface. The change of FT-IR spectra of the deposited film, which can be lifted as a Z-type film, indicates that polycondensation can occur in the monolayer at 10°C without any treatment. The spectrum of the film cast from chloroform hardly changed with time. These results lead to the conclusion that a regular arrangement of monomer molecules in the monolayer, where the amino and ester carbonyl groups are concentrated, is more suitable for the polycondensation. The ester of L-glutamic acid can also form stable monolayers which can be easily deposited on a hydrophobic plate as a Y-type film by the Blodgett technique. The polycondensation of multilayers under an atmosphere of triethylamine was investigated by IR spectroscopy. It indicates that the condensation in multilayers proceeds via intermolecular and intramolecular reactions, by which poly(L-glutamate) derivatives and 2-pyrrolidone derivatives are formed, respectively. The condensation in the bulk crystalline powder gives exclusively the 2-pyrrolidone derivative by intramolecular reaction. These results suggest that the monomer molecules in the multilayers are favorably aligned for the intermolecular reaction, in contrast to the situation in the bulk crystalline powder.     

Synthesis of poly(amino acid)s on molecular assemblies formed by functional active esters of amino acids

The new active β-alanine and glycine esters ( 6 and 7 ) of N-hydroxy-2,3-dihexadecylsuccinimide were prepared and their polycondensation was studied. The aggregation behavior of these esters was examined by an electron microscopy and an osmotic method. They formed multilamella in water and reversed micelle in nonpolar solvents. These solvents were found to be suitable for the polycondensation, which gave the corresponding poly(amino acid)s. The results of polycondensation can be explained by assuming that the aggregations, that is, multilamella in water and reversed micelle in nonpolar solvents, are playing an important role in the polycondensation.     

Synthesis of poly(dipeptide)s on the surface of functional micelle and reversed micelle

Amphiphilic active 4-dodecanoyl-2-nitrophenyl esters of dipeptide containing β-alanine ( 1 – 5 ) were prepared and their polycondensation was studied in detail. The critical micelle concentrations of the active esters 1 – 5 were determined in water by the dye method and the apparent mean aggregation number of reversed micelles formed by model compound 6 was determined by the osmotic method. The results of polycondensation can be explained by assuming that aggregations such as micelle and reversed micelle play an important role in polycondensation. The obtained new poly(dipeptide)s were examined by IR, ¹H NMR, x-ray diffraction, and circular dichroism spectra.     

Room-temperature polycondensation of β-amino acid derivatives. V. Synthesis of hydrophilic polyamide by the polycondensation of β-amino acid derivatives

N-(Hydroxyalkyl) β-alanine ester which was obtained from amino alcohol and acrylate yielded polyamide at room temperature in the presence of a basic catalyst. Alkali and alkali earth metal alkoxides had a strong catalytic effect on the room-temperature polycondensation of N-(hydroxyethyl)-β-alanine esters. The catalytic activity of metal alkoxides decreased in the order: Li > Na > K > Cs and Ca > Zn > Mg. Aluminum and titanium alkoxide had a weak catalytic effect, while boron (III), tin (IV), antimony (V), and tellurium (VI) alkoxides did not show any catalytic activity for the polycondensation. It was also found that solvent had an effect on the course of the polycondensation of N-(hydroxyethyl)-β-alanine esters, and the highest molecular weight polymer was formed only in methanol solution. The solid-phase polycondensation of the low molecular weight prepolymer resulted in a high molecular weight polymer with an inherent viscosity of 1.0 in the presence of a catalytic amount of phosphoric acid. The polymer obtained is hydrophilic and its moisture absorption is more than twice that of nylon 6.     

Controlled polymerization of activated glycine esters by copper(II) chelate

We describe a novel method of polymerization, via the insertion of activated glycine esters into N‐salicylideneglycinato‐aquo‐copper(II) chelate ( 1 ), that uses the reactivity of the metal chelate. In the absence of 1 , a high molecular weight polyglycine was formed as a white precipitate after triethylamine was added to an N,N‐dimethylformamide solution of 4‐nitrophenyl glycinate ( 3a ). In the presence of 5 mol % 1 , however, the polymerization proceeded homogeneously. After the reaction mixture was poured into tetrahydrofuran, a condensation product of glycine was obtained. According to gel permeation chromatography analysis, the product consisted of high and low molecular weight fractions. The former and latter were obtained by self‐polycondensation and polycondensation via the insertion of 3a into 1 , respectively. So that the self‐polycondensation of activated glycinates would be depressed, 2‐chlorophenyl ( 3b ), 3‐chlorophenyl ( 3c ), 4‐chlorophenyl, and phenyl glycinates were used as less activated glycine esters. For the polymerization of 3b and 3c , the polymerization via the insertion of activated glycinates into 1 was promoted. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1504–1510, 2003     

13N-NMR spectroscopy. XXXV. Sequence analysis of alternating and random copolyamides made up of aliphatic and aromatic ω-amino acids

Alternating copolyamides of various ω-amino acids were synthesized by base-catalyzed polycondensation of N-isothiocyanatoacyl ω-amino acids in solution. Derivatives of the following amino acids were used: glycine, β-alanine, γ-aminobutyric acid, δ-aminovaleric acid, ε-aminocaproic acid, D ,L -β-aminobutyric acid, trans-4-aminocyclohexane 1-carboxylic acid, 4-aminophenyl acetic acid, 3-aminobenzoic acid, 4-aminobenzoic acid, 3-amino-4-methyl benzoic acid, and 4-amino-3-methyl benzoic acid. The base-catalyzed polycondensation at lower temperatures gave purer products than the bulk condensation at 180–200°C. ¹³C-NMR and natural-abundance ¹⁵N-NMR spectra measured in trifluoroacetic acid demonstrate that in most cases undisturbed alternating sequences were obtained. Strong neighboring residue effects and long-range sequence effects were found in the ¹⁵N-NMR spectra, and structure/shift relationships are discussed. The sequences of copolyamides obtained by copolymerizations of lactams or β-amino acid N-carboxyanhydrides were investigated by both ¹⁵N-NMR and ¹³C-NMR spectroscopy. ¹³C-NMR spectroscopy was found to be more useful if the copolyamides consist of ω-amino acid units of different chain length. However, ¹⁵N-NMR spectroscopy is more suited if the monomer units differ exclusively by their substituents.     

Acyl iodides in organic synthesis: VIII. Reactions with amino acids

Reactions of acyl iodides RCOI (R=Me, Ph) with glycine, β-alanine, and γ-aminobutyric acid were investigated. The reaction proceeded easily at room temperature without solvent involving both functional groups H₂N and COOH. The prevalence of one of the reaction directions depends on the acidity of the amino acid. The more acidic glycine (pК_a 2.4) reacts with RCOI affording mainly N-acylated product, whereas β-alanine (pК _a 3.60) and especially γ-aminobutyric acid (pК_a 4.06) are predominantly involved into exchange iodination furnishing the corresponding aminoacyl iodides.     

Room-temperature polycondensation of β-amino acid derivatives,I. Polyamide from amino alcohols and acrylates

Acrylates, such as ethyl acrylate, add with amino alcohol to form N-(hydroxyalkyl) β-alanine ester and room-temperature polycondensation follows, forming polyamide in the presence of a basic catalysts, such as alkali metal alkoxide. The reaction medium has an influence on the course of the polycondensation; that is, N-(hydroxyalkyl) polyamide is formed in methanol solution and polyamide ether in other solvents, such as tetrahydrofuran. These two courses of the room-temperature polycondensation have been studied, and the reaction mechanism is discussed in this paper.     

Reversible trans/cis photoisomerization in Langmuir-Blodgett multilayers from polyfunctional azobenzenes

Four novel, amphiphilic, N-acylaminoazobenzene derivatives containing a sulfonyl group and a β-alanine moiety were synthesized and their mono- and multilayers were prepared by the Langmuir-Blodgett (LB) technique. The opto-physical properties of the LB multilayers were investigated. Some relationship between the chemical structure of the azobenzenes and photosensitivity of their LB multilayers has been found. Reversible trans/cis photoisomerization was observed on alternate irradiation with ultraviolet and visible light of LB multilayers from azobenzenes modified by the introduction of a second aliphatic chain in the N-acylamino fragment as well as by introduction of the bulky N,N′-dicyclohexyl urea moiety.     

Alkylation of Imidazolidinone Dipeptide Derivatives: Preparation of Enantiomerically Pure Di- and Tripeptides by ‘Chirality Transfer’ via a Pivalaldehyde N,N-Acetal Center. Preliminary Communication

Glycylglycine, glycyl-(S)-alanine, and (S)-alanylglycine esters are cyclized through pivalaldehyde imines to give dipeptide-derived 3-(benzyloxycarbonyl)-2-(tert-butyl)-5-oxoimidazolidine-1-acetates 1 – 3 . These are alkylated diastereoselectively by Li-enolate formation and addition of alkyl bromides or iodides (products 4 – 6 ). Starting from (S)-alanine and glycine, (S)-alanyl-(S)-alanine or (R)-alanyl-(R)-alanine, and (R)-alanyl-(R)alanyl-(S)-alanine- have thus been prepared, with the (tert-butyl)-substituted N,N-acetal center playing the role of a pivot or lever for diastereoselective formation of new stereogenic centers under kinetic or thermodynamic control.     

Fluorine containing poly(amide-imide)s: synthesis and formation of Langmuir-Blodgett monolayers

Soluble fluorine containing poly(amide-imide)s, PAI(1-4), were synthesized from diimide-dicarboxylic acid, 2,2-bis[N-(4-carboxyphenyl)-phthalimide-1,4-yl]hexafluoropropane with various diamines by direct polycondensation in N-methyl-2-pyrrolidone (NMP) containing CaCl₂ and using triphenyl phosphite and pyridine as condensing agents. The polymers were readily soluble in aprotic polar solvents such as NMP, N,N-dimethylacetamide, dimethyl sulfoxide and tetrahydrofuran. Their Langmuir monolayers were studied at the air/water interface. The monolayers were generally stable at the water surface and could be reproducibly transferred onto solid substrates to build up Langmuir-Blodgett (LB) multilayers. The LB mono- and multilayers were characterized by ultra-violet/visible spectroscopy (UV-Vis), surface plasmon resonance, atomic force microscopy.     

Room-temperature polycondensation of β-amino acid derivatives VI. Synthesis of various N-(hydroxyethyl) nylons

Various N-(hydroxyethyl)amino acid esters having a methyl substituent or phenyl group between amine and ester groups have been synthesized and their polycondensation behavior was investigated. These substituted amino acid esters gave amorphous polyamides which were soluble in alcohol. A model reaction between N-(hydroxyethyl)-amine and carboxylic acid ester was carried out in order to elucidate the role of hydroxyethyl group on the polycondensation. It was found that the amidation reaction took place rapidly at room temperature when the alkyl group of the carboxylic acid was small. N-(Hydroxyethyl) polyamides were obtained from N,N′-(bishydroxyethyl)-dicamines and dicarboxylic acid esters. The reaction mechanism of the room-temperature polycondensation reaction is discussed.     

Polycondensation of bis(p-nitrophenyl) β-truxinate with diamine

Model reaction of bis(4-nitrophenyl) β-truxinate (BNPT) with aliphatic amines proceeded quantitatively at room temperature. Accordingly, polycondensation of BNPT with various diamines was carried out at room temperature or 80°C. During the polycondensation of BNPT with diamines, the precipitation of polymer or the observed gelation of polymerization solution occurred, which may limit the molecular weight of the polymer. On the other hand, the reaction of BNPT with 1,3-(4-piperidyl)propane (DPP) proceeded homogeneously to give the polymer with relatively high molecular weight, and the obtained polyamide (P-1e) showed excellent solubility in many solvents. The study of TG and DTA indicated that the obtained polymers were stable at lower temperature than around 270°C. The polymer prepared from the polycondensation of BNPT with hexamethylenediamine showed melting point and decomposition due to the imidation at 282°C. The photochemical reaction of these polymers was carried out in the film state. The irradiation of 254 nm light caused an absorption at 272 nm to appear and the molecular weight to decrease. This meant that the scission of cyclobutane ring in the main chain occurred to give cinnamamide structures. Also, the absorption at 272 nm decreased by the irradiation of 302.5 nm light. However, the UV spectrum of irradiated polymer did not agree with that of the original polymer. These results suggested that the dimerization of the resulting cinnamamide moieties occurred in the competition of their trans–cis-isomerization. On the other hand, the rate of scission of cyclobutane ring of P-1e was faster than that of the corresponding polyamide containing α-truxillamide structure.     

Effect of chelation on the polycondensation of monomers having an active ester group

Various amino acid esters and dicarboxylic acid esters having a β-thioether group have been synthesized and their polycondensation with diamine was found to occur at room temperature to form polyamide thioether. The effect of solvents or chelating agents on their polycondensation reaction was investigated. Metal acetylacetonates or inorganic salts had a great influence on the rate of the polycondensation reaction, and the catalytic activity of metal acetylacetonates M(AcAc)_n or inorganic salts decreased in the following order: Mg(AcAc)₂?Th(AcAc)₄>Cu(AcAc)₂>Li(AcAc)>None>Zr(AcAc)₄, MgCl₂·6H₂O>CuCl₂·.2H₂O>ZnCl₂>MgCl₂>None. It was also found that the amount of polyamide thioether was dependent on solvents or the presence of chelating agents because the polycondensation rate and the apparent equilibrium between ring and chain structures were both greatly influenced by solvents or chelating agents. These effects of solvents or chelating agent on the polycondensation may be attributable to formation of a complex with the thioether group which enhances the reactivity of ester.     

Domino synthesis of pyrimido and imidazoquinazolinones

A simple method for the synthesis of N-alkyl-2-arylquinazolin-4-amines, methyl 4-((2-arylquinazolin-4-yl)amino) butanoates, 6-aryl-2,3-dihydro-4H-pyrimido[1,2-c]quinazolin-4-ones, and 5-arylimidazo[1,2-c]quinazolin-3(2H)-ones has been described. It involves a simple reaction of N-(2-cyanophenyl)-substitutedbenzimidoyl chlorides with alkylamine, γ-aminobutyric acid, β-alanine, l -alanine, and glycine methyl esters hydrochloride in acetonitrile to afford the desired compounds after a series of instantaneous reactions that include Dimroth rearrangement. The reaction involves reflux for 12 hours, simple addition of reagents to an in situ generated benzimidoyl chloride, and simple workup, to form 21 examples of pure compounds in high yields. The active intermediate N-(2-cyanophenyl)-substitutedbenzimidoyl chlorides were formed by the reaction of N-(2-cyanophenyl)-substitutedbenzamides with thionyl chloride in a one-pot strategy. The alternative method described for this preparation deals with an exhausting multistep reactions starting from anthranilic acid.     

Synthesis and physiological activity of trialkyl phosphorothioates and trialkyl phosphorodithioates containing fragments of N-acylated amino acids

A series of S-[N-acyl-N-(alkoxycarbonylalkyl)aminomethyl] O,O-dialkyl phosphorothioates and -dithioates were prepared by the reactions of the corresponding alkali salts of dialkyl phosphorothioates or dialkyl phosphorodithioates with esters of N-acyl-N-(chloromethyl)glycine or N-acyl-N-(chloromethyl)--alanine and by the reactions of dialkylphosphorothioic or dialkylphosphorodithioic acids with N-acylated amino acids or their esters and paraformaldehyde in the presence of gaseous HCl. Some of the resulting compounds proved to be active permethrine synergists.     

Investigation of the effects of various parameters on the synthesis of oligopeptides in aqueous solution

Oligomerization efficiency of amino acids in aqueous solution has been compared under different conditions (temperature, activating agent, etc.) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 1,1^′-carbonyldiimidazole (CDI) as coupling agents. Glycine (H₂N-CH₂-COOH) and α-alanine (H₂N-CH(CH₃)-COOH) were chosen as α-amino acids and β-alanine (H₂N-CH₂-CH₂-COOH) as the β-amino acid. The coupling reaction between EDC and glycine was shown to occur but does not go to completion either at ambient temperature or at 70 °C. The presence of a carboxylic activating agent such as N-hydroxysuccinimide improves the EDC-mediated coupling reaction, and the amino acid structure (α- or β-) was shown to have an influence on the oligomerization efficiency, with β-alanine polymerisation being more efficient. These findings are explained by reference to the reaction mechanism.     

用DCC/DMAP合成N-苄氧羰基氨基酸薄荷酯

以乙腈为溶剂, 用DCC/DMAP偶合法合成了5个N-苄氧羰基氨基酸薄荷酯, 产率90%～94%. 起始原料氨基酸包括: 甘氨酸, DL-蛋氨酸, β-丙氨酸, L-缬氨酸和L-脯氨酸. 给出了目标产物的氢谱、碳谱、红外光谱、质谱、高分辨质谱和元素分析数据.     

Solvent Effects on the Protonation Constants of Some <Emphasis Type="Italic">α</Emphasis>-Amino Acid Esters in 1,4-Dioxane–Water Mixtures

The stoichiometric protonation constants of some α-amino acid esters (glycine methyl ester, glycine t-butyl ester, l-valine methyl ester, l-valine ethyl ester, l-valine t-butyl ester, l-serine methyl ester, l-serine ethyl ester, l-leucine methyl ester, l-leucine ethyl ester, l-leucine t-butyl ester, l-alanine methyl ester, l-alanine benzyl ester, l-phenylalanine methyl ester, l-phenylalanine ethyl ester, and l-phenylalanine t-butyl ester) in water and 20%, 40%, and 60% (v/v) 1,4-dioxane–water mixtures have been determined at an ionic strength of 0.10 mol⋅L⁻¹ NaCl and at 25.0±0.1 °C under a nitrogen atmosphere. A potentiometric method was used and the calculation of the protonation constants has been carried out using the BEST computer program. The results were discussed in terms of macroscopic properties of the mixed solvent. The stoichiometric protonation constants were influenced by changes in solvent composition and their variations were discussed in terms of preferential solvation. Also, knowledge the protonation constant of α-amino acid esters will be helpful when determining the microscopic equilibrium constants of their corresponding amino acids.     

Polycondensation of α‐amino acid esters in the presence of yttrium triflate as a Lewis acid

To develop polycondensation methods for poly(α‐amino acid)s, we describe a first examination to use yttrium triflate as a Lewis acid for polycondensation of α‐amino acid esters. In the absence of Lewis acid, no polycondensation of 2‐methoxyphenyl glycinate ( 1b ) at room temperature proceeded. While the polycondensation of 1b was carried out with 5 mol % yttrium triflate, a condensation product of glycine was obtained in 16% yield. Although polycondensation of 4‐nitrophenyl L ‐leucinate ( 1c ) and 4‐nitrophenyl L ‐valinate ( 1d ) were also promoted with 5 mol % yttrium triflate, the condensation products of both α‐amino acid esters were obtained in only a few percent yield. When 1d was polymerized in the presence of 100 mol % yttrium triflate, high molecular weight poly(L ‐valine) was obtained in 91% yield. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4731–4735, 2006