Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. I. Synthesis of 1,5-disubstituted 4-acylpyrazoles

Reaction of open-chain and cyclic sym-1,3-diones with N,N-dimethylformamide dimethyl acetal gave, generally in high yield, a series of sym-2-dimethylaminomethylene-1,3-diones which reacted with phenylhydrazine and methylhydrazine to afford, generally in satisfactory yield, a number of 1,5-disubstituted 4-acylpyrazoles. The applications and limits of this new pyrazole synthesis are presented and discussed.     

Diastereo- and Enantioselective Mannich/Cyclization Cascade Reaction Access to Chiral Benzothiazolopyrimidine Derivatives

An efficient asymmetric Mannich/cyclization cascade strategy was established from 2-benzothiazolimines with N-acylpyrazoles to provide optical active benzothiazolopyrimidine derivatives using a copper-based complex. The mild cascade process constructed various structurally diverse products with broad scope of substrates together with excellent enantioselectivities (up to 99 % ee) and diastereoselectivities (up to 99:1 d.r.).     

Chemical properties ofN-(amidomethy)- andN-(imidomethyl)glycine derivatives 2. Reactions at alkoxycarbonyl and carboxyl groups

N-(Aroylarnmomethylfglycine amides were synthesized by reactions ofN-(aroyllminomethyl) glycine esters with ammonia. Alkaline hydrolysis ofN-(amidomethyl)glycine,N-(irnidornethyl)glycine, andN-(amidomethyl)pheriylalariiiie esters afforded the correspondingN-(amidowthyVa-amirio acids- Reactions of the Last-mentioned compounds with ethyl esters of glycine, alanine, and phenylalanine in the presence of dicyclohexylcarbodiimide yielded dipeptides containingNh-amidomethyl substituents.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1770–1771, July, 1996.     

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.     

Synthesis and biological activity of some new 3-and 6-substituted coumarin amino acid derivatives. Part I

The synthesis of 6-nitrocouarrain-3-CO-amino acids and their corresponding methyl esters (II-XVII) and some dipeptide methyl esters (XVIII-XXVI) are described. 6-(N-Tosyl- or N-phthalylaminoacyl)aminocoumarin-3-carboxylic acid methyl esters (XXXIV-XL) and 3-(N-phthalyl- or N-tosylaminoacytyaminocoumarins (XLV-LVI) have been prepared via the carbodiimide and acid chloride methods. Hydrazinolysis of 3- or 6-(N-phthalylaminoacyl)aminocoumarin derivatives in tetraline gave the corresponding 3- and 6-(aminoacyl)aminocoumarins and the carboxylic acid hydrazides (XLI-LVIII), respectively. 3-(N-Tosyl-L-Val-L-Leu-)aminocoumarin (LIX) was synthesized via the azide method. Twenty four of various substituted 3- and 6-aminoacylcoumarin derivatives were found to possess specific antimicrobial activities towards different microorganisms.     

Chemical properties ofN-(amidomethyl)- andN-(imidomethyl)glycine derivatives

N-Nitroso,N-sulfonyl, andN-acyl derivatives ofN-(amidomethyl)- andN-(imidomethyl)-glycine esters have been synthesized by the reactions of these esters with HNO₂ or with sulfonylating and acylating reagents.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1299–1305, July, 1995.     

2-Benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxy-carbonylvinyl-1 as N-protecting groups in peptide synthesis. Their application in the synthesis of dehydropeptide derivatives containing N-terminal 3-heteroarylamino-2,3-dehydroalanine

Ethyl 2-benzoyl-3-dimethylaminopropenoate ( 6 ) and methyl 2-benzoylamino-3-dimethylaminopropenoate ( 46 ) were used as reagents for the protection of the amino group with 2-benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxycarbonylvinyl groups in the peptide synthesis. Reactions of ethyl 2-benzoyl-3-dimethylaminopropenoate (6) with α-amino acids gave N-(2-benzoyl-2-ethoxycarbonylvinyl-1)-α-amino acids 13–19. These were coupled with various amino acid esters to form N-(2-benzoyl-2-ethoxycar-bonylvinyl-1)-protected dipeptide esters 20–31. The removal of 2-benzoyl-2-ethoxycarbonylvinyl-1 group, which was achieved by hydrazine monohydrochloride or hydroxylamine hydrochloride, afforded hydrochlo-rides of dipeptide esters 32–41 in high yields. Similarly, the substitution of the dimethylamino group in methyl 2-benzoylamino-3-dimethylaminopropenoate ( 46 ) by glycine gave N-(2-benzoylamino-2-methoxycar-bonylvinyl-1)glycine ( 47 ), which was coupled with glycine ethyl ester to give N-[N-(2-benzoylamino-2-methoxycarbonylvinyl-1)glycyl]glycine ethyl ester ( 48 ). Treatment of 48 with 2-arnino-4,6-dirnethylpyrimi-dine afforded N-[glycyl]glycine ethyl ester hydrochloride (34) in high yield. Amino acid esters and dipeptide esters were employed in the preparation of tri- 58-70, tetra- 71–82, and pentapeptide esters 83–85 containing N-terminal 3-heteroarylamino-2,3-dehydroalanine. 2-Chloro-4,6-dimethoxy-1,3,5-triazine was employed as a coupling reagent for the preparation of peptides 58–85.     

1,2,3-thiadiazoles. I. Synthesis of sodium (or potassium) 1,2,3-thiadiazole-4-thiolates via thiocarbazonate esters and N-acylthiohydrazonate esters

A general synthesis of 1,2,3-thiadiazole-4-thiolates 1 and their derivatives 2–3 by an extension of the Hurd-Mori 1,2,3-thiadiazole synthesis is described. Treatment of methyl (or ethyl) [1-(alkylthio)alkylidene]hydrazinocarboxylates 11 (thiocarbazonate esters) or other N-acylthiohydrazonate esters [Y = ureido ( 12 ) or arenesulfonyl ( 13 )] with thionyl chloride affords 2–3 efficiently. Intermediates 11–13 are readily obtained from the N²-thioacylcarbazates 8 , N³-thioacylsemicarbazides 9 , or N²-thioacyl-N¹-(p-toluenesulfonyl)hydrazides 10 , respectively, by S-alkylation. Physicochemical properties of the 1,2,3-thiadiazoles 1–3 and N-acylthiohydrazonate esters 11–13 are also described.     

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.     

Microwave-promoted solvent-free synthesis of N-(diphenylmethylene)glycine alkyl esters

The efficient synthesis of N-(diphenylmethylene) glycine alkyl esters was achieved for the first microwave irradiation under solvent-free condition, using PEG or quaternary ammonium salts as phase transfer catalysts (PTCs). Under the optimum conditions, N-(diphenylmethylene) glycine alkyl esters were obtained in excellent yields in most cases.     

Mass spectrometry of some methyl esters of N-4-pyrimidinylamino acids: Rearrangements of the ions occurring on electron-impact ionization

The electron-impact-induced mass fragmentations of methyl esters of N-(1H-2-oxo-4-pyrimidinyl)ainino acids are reported. The loss of a ·COOCH₃ radical and the elimination of a methanol molecule were observed and possible mechanisms of these processes are proposed. The loss of a ·COOH radical and elimination of water were established, which suggests the rearrangement of the investigated esters into isomeric N-4-pyrimidinylamino acids.     

Syntheses and reactions of functional polymers. XCIII. Syntheses of polymers containing the N-(4-hydroxy-3-nitrophenyl)succinimide structure in the chain and the use of these activated polymer esters of N-blocked amino acids or peptides

Polymers containing the N-(4-hydroxy-3-nitrophenyl)succinimide residue were designed in order to achieve acyl activation of a reacting carboxylic acid in the solid phase. These polymers were prepared through the following three routes: (a) styrene was allowed to copolymerize with N-(4-hydroxy-3-nitrophenyl)- or N-(4-acetoxy-3-nitrophenyl)maleimide, (b) styrene was copolymerized with N-(4-acetoxyphenyl)maleimide in the presence of divinylbenzene (DVB), and the copolymer obtained was hydrolyzed and nitrated, (c) a copolymer of maleic anhydride and styrene was reacted with p-aminophenol, followed by nitration. The polymers prepared by routes b and c were converted to the activated polymer esters of N-blocked amino acids and peptides by using dicyclohexylcarbodiimide (DCC). The acylated polymers thus obtained were treated with amino acid esters and found to give peptides quantitatively without racemization.     

The chemistry of polycyclic arene imines. VII. Reactions of phenanthrene 9,10-imine with aromatic carboxaldehydes,carboxylic acids and acetylenic esters

The reactions of phenanthrene 9,10-imine ( 1 ) with aromatic aldehydes, benzoic acids and acetylenedi-carboxylic esters were investigated. The aldehydes were shown to give 1-[N-(arylmethylidene)-9-phenanthreneamine-10-yl]-1a,9b-dihydrophenanthro[9,10-b]azirine 2. The ‘dimeric’ structure of these products was established by X-ray diffraction analysis. The carboxylic acids proved to form in the presence of dicyclohexylcarbodiimide, N-aroylphenanthrene 9,10-imines 7 , that readily undergo rearrangement to N-aroyl-9-phenanthrenamines 8. Esters of acetylenedicarboxylic acid gave the corresponding esters of (Z)-2-(1a,9b-dihydrophenanthro[9,10-b]azirine-1-yl)-2-butendioic acid 10 .     

Polycyclic nitrogen compounds. Part I. Synthesis of new heterotricyclic quinoxalinones with bridgehead nitrogen atoms

New tricyclic quinoxalinone skeletons with a fully-reduced ring ‘C’ -1,2,3,3a-tetrahydropyrrolo[1,2-α]quin-oxalin-4-one (I-II) and 7,8,9,10-tetrahydropyrido[1,2-α]quinoxalin-6-one (III-IV) derivatives were obtained by selective hydrogen transfer reductive cyclisation of N-(2-nitrophenyl)pyrrolidine-2-carboxylic acid esters and N-(2-nitrophenyl)piperidine-2-carboxylic acid esters (VIa,b and VIIIa,b), respectively.     

New coupling reagents for homogeneous esterification of cellulose

A group of known, but in cellulose chemistry new coupling reagents for homogeneous esterification has been investigated: 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride, N-methyl-2-bromopyridinium iodide, N-methyl-2-chloropyridinium iodide, and N-methyl-2-bromopyridinium tosylate. In order to study their ability to activate carboxylic acids in esterifications of cellulose they have been employed in synthesis of cellulose adamantate esters. Their effectiveness has been estimated in terms of degree of substitution of resulting esters and compared to that obtained with the commonly used N,N′-carbonyldiimidazole.     

Reactions of N-substituted pyridinium carbamoylmethylenides with ethyl arylidenecyanoacetates

Condensation of pyridinium N-alkyl-, N-cycloalkyl-, N-benzyl-, and N-phenethylcarb-amoylmethylenides with ethyl arylidenecyanoacetates stereoselectively gives 4,5-trans-1-alkyl-, 4,5-trans-l-cycloalkyl-, 4,5- trans-1-benzyl-, and 4,5-trans-1-phenethyl-4-aryl-3-cyano-6-oxo-5-(3-R-1-pyridinio)-1,4,5,6-tetrahydropyridin-2-olates. However, pyridinium N-arylcarb-amoylmethylenides react with the same esters without ring closure, yielding Michael adducts, viz., ethyl 3-aryl-4-(N-arylcarbamoyl)-2-cyano-4-(1-pyridinio)butyrates.     

Reaction of the Reformatskii reagent obtained from bromotetrahydrofuran-2-one with 2-oxochromene-3-carboxylic or 3-oxo-3<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">f</Emphasis>]chromene-2-carboxylic acid derivatives

The Reformatskii reagent obtained from 3-bromotetrahydrofuran-2-one reacts with alkyl esters of 6-bromo- and 6,8-dibromo-2-oxochromene-3-carboxylic acid or alkyl esters and N-benzylamide of 3-oxo-3H-benzo[f]chromene-2-carboxylic acid to form alkyl esters of 6-bromo- and 6,8-dibromo-2-oxo-4-(2-oxotetrahydrofuran-3-yl)chroman-3-carboxylic acid or alkyl esters and N-benzylamide of 2,3- dihydro-3-oxo-1-(2-oxotetrahdrofuran-3-yl)-1H-benzo[f]chromene-2-carboxylic acid as a mixture of two diastereomers.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 9, 2004, pp. 1513–1515.Original Russian Text Copyright © 2004 by Shchepin, Fotin, Shurov.This revised version was published online in April 2005 with a corrected cover date.     

Studies on pyrrolidinones. Synthesis of some bioisosteres of 3,3,5-trimethylcyclohexyl pyroglutamate

The synthesis of new N-(4-chlorobenzyl) and N-(4-chlorobenzoyl)pyroglutamic esters and amids whose the structure conserves the main structural features of the cholesterol lowering agent crilvastatin is described.     

ω-苯基-(2S)-N-叔丁氧羰基氨基酸乙酯的制备

格氏试剂和N-叔丁氧羰基焦谷氨酸乙酯反应生成中间体ω-苯基-δ-氧代-(2S)-N-叔丁氧羰基氨基酸乙酯, 分别用对甲基苯磺酰肼和醋酸硼氢化钠结合的一锅法还原或Pd/C催化氢化还原中间体得到ω-苯基-(2S)-N-叔丁氧羰基氨基酸乙酯.     

Novel Bulky Esters of Biopolymers: Dendritic Cellulose

Dendronized cellulose derivatives are discussed. Regarding our own studies, novel bulky esters of cellulose were synthesized homogeneously in N,N- dimethyl acetamide/LiCl or dimethyl sulfoxide in combination with fluoride ions by conversion of the biopolymer with 3,5-dihydroxybenzoic acid based aryl polyester dendrons. The carboxylic acid moieties were efficiently activated in situ with N,N′-carbonyldiimidazole or the acid chloride was applied. Cellulose esters with values of the degree of substitution of up to 0.7 were obtained. The functionalization analyzed by NMR spectroscopy occurs not only at position 6 (primary hydroxyl group) but also the secondary one at position 2.