Reaction of N-Acyl-α-triphenylphosphonio-α-amino Acid Esters with Organic Bases: Mechanism of the Base-Catalyzed Nucleophilic Substitution of the Triphenylphosphonium Group

Summary.  Reactions of N-acyl-α-triphenylphosphonio-α-amino acid methyl esters with organic bases (triethylamine or DBU) were investigated as the crucial step of the base-catalyzed displacement of the triphenylphosphonium group by nucleophiles. It was proved that N-acyl-α-triphenylphosphonioglycinates are transformed to an equilibrium mixture of the corresponding N-acyliminoacetates and N-acyl-α-triphenylphosphoranylidene glycinates by bases. In the case of N-acyl-α-triphenylphosphonio-α-amino acid esters with quaternary α-carbon, the α-substituted homologues of the N-acyliminoacetates were detected to be the only primary reaction product which, however, can undergo further tautomerization to the corresponding α,β-dehydro-α-amino acid derivatives. In both these cases the reaction of N-acyl-α-triphenylphosphonio-α-amino acid esters with nucleophiles proceeds via the addition of a nucleophile to the activated C=N double bond of the N-acylimino intermediate. Corresponding author. E-mail: romanm@zeus.polsl.gliwice.pl Received October 31, 2001. Accepted (revised) December 17, 2001     

Synthesis of Derivatives of ω-Isocyanato-α-methylamino, ω-Ureido-α-methylamino, and Nα-Methyl-α, ω-diamino Acids

 Homochiral N^α-methyl-2,3-diaminopropionic and N^α-methyl-2,4-diaminobutyric acid derivatives 8a,b were obtained via a stereoconservative four-step synthesis starting from hexafluoroacetone protected L-aspartic and L-glutamic acid 2a,b, respectively. Hexafluoroacetone protected ω-isocyanato-α-methylamino acids 4a,b– the key intermediates of the synthesis – are versatile building blocks for amino acid and peptide modification and promising candidates for combinatorial chemistry. Upon reaction with alcohols, compounds 4 give activated N ^ω-urethane protected ω-amino-α-methylamino acid derivatives 5–7; upon reaction with amines, ω-ureido-α-methylamino acid derivatives 10–12 and 3-methylamino-pyrrolidin-2-ones 13 are available.     

Thiocarbamoylation of amine-containing compounds

Thiocarbamoylation of 5-aminosalicylic acid with tetramethylthiuram disulfide afforded 5-(N′,N′-dimethylthioureido)salicyclic acid. Treatment of the latter with mineral acids or Ac₂O gave 5-isothiocyanatosalicylic acid whose reaction with ethanolamine yielded 5-[N′-(2-hydroxyethyl)thioureido]salicylic acid. The latter underwent cyclization under the action of TsOH to form 5-(2-thiazolin-2-ylamino)salicylic acid. For Part 2, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2315–2318, December, 1999.     

Dissolution of pure and substituted goethites controlled by the surface reaction under conditions of abrasive stripping voltammetry

Pure goethites and Al-, Cr-, and Mn-goethites, as synthetic and natural products, were used to establish the conditions for electrochemical reductive dissolution following surface reaction kinetics. In diluted perchloric acid and at reaction rate coefficients of the order of 10⁻⁴s⁻¹, the γ parameters in the kinetic equation J/N ₀ = k(N/N ₀)^γ (where J is the reaction rate and N and N ₀ are actual and total molar amounts of a solid reactant) were in the range expected for the shape-preserving dissolution of the particles with a certain size and reactivity distribution function. The same range of γ was found using the dissolution of goethites by a chemical reaction via oxalate-ferrous ion surface complexation. The importance of the charge transfer coefficient to describe the iron oxide reactivitie s was highlighted as it is sensitive to the synthetic route and also to the substitution of iron. Received: 20 December 1996 / Accepted: 24 February 1997     

A Simple Synthesis of Stable 1,4-Diionic Pyridinium Betaines

Summary.  Protonation of the reactive intermediate produced in the reaction between pyridine and dialkyl acetylenedicarboxylates by strong CH-acids such as N,N′-dimethylbarbituric acid, Meldrum’s acid, or indane-1,3-dione leads to a vinylpyridinium cation which undergoes an addition reaction with the enolate anion of the CH-acid to produce stable 1,4-diionic pyridinium betaines in good yields. Corresponding author. E-mail: isayavar@yahoo.com Received February 5, 2002. Accepted (revised) March 12, 2002     

Synthesis of Derivatives of ω-Isocyanato-α-methylamino, ω-Ureido-α-methylamino,and N<Superscript>α</Superscript>-Methyl-α, ω-diamino Acids

Summary.  Homochiral N^α-methyl-2,3-diaminopropionic and N^α-methyl-2,4-diaminobutyric acid derivatives 8a,b were obtained via a stereoconservative four-step synthesis starting from hexafluoroacetone protected L-aspartic and L-glutamic acid 2a,b, respectively. Hexafluoroacetone protected ω-isocyanato-α-methylamino acids 4a,b– the key intermediates of the synthesis – are versatile building blocks for amino acid and peptide modification and promising candidates for combinatorial chemistry. Upon reaction with alcohols, compounds 4 give activated N ^ω-urethane protected ω-amino-α-methylamino acid derivatives 5–7; upon reaction with amines, ω-ureido-α-methylamino acid derivatives 10–12 and 3-methylamino-pyrrolidin-2-ones 13 are available. Received November 17, 1999. Accepted November 26, 1999     

Rearrangement of N-(3-pyridyl)nitramine

Contrary to other N-(pyridyl)nitramines, the title compound cannot be rearranged to 3-amino-2-nitropyridine or other isomers. Hypothetical products of its transformation under influence of concentrated sulphuric acid, viz. 3-hydroxypyridine, 3,3′-azoxypyridine and 3,3′-azopyridine, were obtained from 3-nitro- and 3-aminopyridine in oxidation and reduction reactions. N-(3-Pyridyl)nitramine was prepared and rearranged in concentrated sulphuric acid. 3-Hydroxypyridine and 3,3′-azoxypyridine were isolated from the reaction mixture, other products were identified by the HPLC and GCMS methods. The results indicate that N-(3-pyridyl)hydroxylamine is an intermediate formed from N-(3-pyridyl)nitramine under the influence of concentrated sulphuric acid. The reaction path, leading to the final products, is discussed in context of the mechanism of nitramine rearrangement.     

On the Reaction between Alkyl Isocyanides and Ethynyl Phenyl Ketone in the Presence of N , N ′-Dimethylbarbituric Acid

 The reactive 1:1 intermediate produced in the reaction between alkyl isocyanides and ethynyl phenyl ketone was trapped with N,N ′-dimethylbarbituric acid to produce alkyl 1,3-dimethyl-2,4-dioxo-7-phenyl-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-5-carboxamides in good yields.     

Strongly fluorescent dipyrrinones. Internal quenching

Yellow N,N′-carbonyl-bridged dipyrrinones can generally be prepared from dipyrrinones simply by reaction with N,N′-carbonyldiimidazole in the presence of a strong, non-nucleophilic base. They are typically intensely fluorescent, with fluorescent quantum yields approaching 1.0. In an effort to shift the excitation wavelength, and thus the fluorescence emissions, strongly to the red, we prepared bridged dipyrrinones conjugated with thiobarbituric acid and Meldrum’s acid substituents at C-9. Such conjugation causes the dipyrrinones to have a magenta color (absorption wavelength shifted from ∼400 nm of a typical dipyrrinone to ∼550 nm of the dipyrrinone conjugate). For comparison, we also prepared analogs with formyl, carboxyl, acrylate, and acetyl substituents at C-9. Unexpectedly and uniquely, the 9-CHO substituent caused the fluorescence quantum yield to drop to ∼10⁻³ while carboethoxy substituent exerted only a minor influence.     

Synthesis of azoles from 3,3′-[(4-alkoxyphenyl)imino]bis(propanoic acid hydrazides)

Abstract  

Reaction of 3,3′-[(4-alkoxyphenyl)imino]bis(propanoic acid hydrazides) with CS₂ in alkaline solution and subsequent acidification gave 5,5′-[[(4-alkoxyphenyl)imino]diethane-2,1-diyl]bis(1,3,4-oxadiazole-2(3H)-thiones). The same dihydrazides on reaction with phenyl isocyanates or phenyl isothiocyanates were converted to bis[N′-(phenylaminocarbonyl)propanoic acid hydrazides] and bis[N′-(phenylaminocarbonothioyl)propanoic acid hydrazides], which underwent cyclization in alkaline medium to produce 5,5′-[[(4-alkoxyphenyl)imino]diethane-2,1-diyl]bis(4-phenyl-2,4-dihydro-3H-1,2,4-triazol-3-ones) and their 3-thio analogues, whereas in sulfuric acid or POCl₃ 5,5′-[[(4-alkoxyphenyl)imino]diethane-2,1-diyl]bis(N-phenyl-1,3,4-oxadiazol-2-amines) and 5,5′-[[(4-alkoxyphenyl)imino]diethane-2,1-diyl]bis(N-phenyl-1,3,4-thiadiazol-2-amines) were obtained.     

<Emphasis Type="Italic">N</Emphasis>-alkylation of amidothiophosphoryl compounds under phase-transfer catalysis conditions. Synthesis and properties of 1,3,2-thiazaphosphacyclanes

N (ω-Haloalkyl)amidothiophosphates, N (ω-Haloalkyl)amidothiophosphonates, and N- (ω-Haloalkyl)amidothiophosphinates (Hal = Cl or Br) were obtained in high yields by alkylation of phosphorus(V) acid thioamides with 6h,ω-dihaloalkanes under phase-transfer catalysis (PTC) conditions or through the use of NaH as a base. Thermal rearrangement of N (3-iodopropyl)-or N (4-iodobutyl)amidothiophosphate and N (3-iodopropyl)-or N (4-iodo-butyl)amidothiophosphonate obtained in situ by the Finkelstein reaction provides a convenient route to 2-oxo-1,3,2-thiazaphosphinanes and 2-oxo-1,3,2-thiazaphosphepanes. Reactions of N (ω-Haloalkyl)amidothiophosphinates with NaClO₄ in MeCN afforded the first example of stable 1,3,2-thiazaphosphacyclanium salts containing P—C bonds.     

Deamination of Some N-Amino Nitrogen Heterocycles Using Preyssler’s Anion

Summary. Some N-aminotriazines and -triazoles were treated with Preyssler’s anion as catalyst in acetic acid to afford the corresponding deaminated triazines and triazoles. The reaction is suggested to proceed via formation of N-nitrosamines with subsequent N–NO bond cleavage.     

A Cyclodextrin Self-Assembled Monolayer (SAM) Based Surface Plasmon Resonance (SPR) Sensor for Enantioselective Analysis of Thyroxine

Heptakis 6-deoxy-6-[12-(thiododecyl) undecanamido-β-cyclodextrin has been produced by reaction of Heptakis(6-deoxy-6-amino)-β-cyclodextrin and 12-(thiododecyl)undecanoic acid using O-Benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) as activating agent. Self-assembled monolayers of this macrocycle have been used in a surface plasmon resonance (SPR) sensor; it has been shown that this system is suitable to discriminate between d and l enantiomers of thyroxine, with a greater affinity for the d-enantiomer. Received in final form: 6 January 2005     

On the Reaction between Alkyl Isocyanides and Ethynyl Phenyl Ketone in the Presence of N,N′-Dimethylbarbituric Acid

Summary.  The reactive 1:1 intermediate produced in the reaction between alkyl isocyanides and ethynyl phenyl ketone was trapped with N,N ′-dimethylbarbituric acid to produce alkyl 1,3-dimethyl-2,4-dioxo-7-phenyl-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-5-carboxamides in good yields. Corresponding author. E-mail: isayavar@yahoo.com Received January 8, 2002. Accepted January 14, 2002     

Strongly fluorescent dipyrrinones. Internal quenching

Yellow N,N′-carbonyl-bridged dipyrrinones can generally be prepared from dipyrrinones simply by reaction with N,N′-carbonyldiimidazole in the presence of a strong, non-nucleophilic base. They are typically intensely fluorescent, with fluorescent quantum yields approaching 1.0. In an effort to shift the excitation wavelength, and thus the fluorescence emissions, strongly to the red, we prepared bridged dipyrrinones conjugated with thiobarbituric acid and Meldrum’s acid substituents at C-9. Such conjugation causes the dipyrrinones to have a magenta color (absorption wavelength shifted from ∼400 nm of a typical dipyrrinone to ∼550 nm of the dipyrrinone conjugate). For comparison, we also prepared analogs with formyl, carboxyl, acrylate, and acetyl substituents at C-9. Unexpectedly and uniquely, the 9-CHO substituent caused the fluorescence quantum yield to drop to ∼10⁻³ while carboethoxy substituent exerted only a minor influence. Correspondence: David A. Lightner, Department of Chemistry, University of Nevada, Reno, 89557 Nevada, USA.     

Study on mechanism for oxidation of <Emphasis Type="Italic">N,N</Emphasis>-dimethylhydroxylamine by nitrous acid

The oxidation of N,N-dimethylhydroxylamine (DMHAN) by nitrous acid is investigated in perchloric acid and nitric acid medium, respectively. The effects of H⁺, DMHAN, ionic strength and temperature on the reaction are studied. The rate equation in perchloric acid medium has been determined to be −d[HNO₂]/dt = k[DMHAN][HNO₂], where k = 12.8 ± 1.0 (mol/L)⁻¹ min⁻¹ when the temperature is 18.5 °C and the ionic strength is 0.73 mol/L with an activation energy about 41.5 kJ mol⁻¹. The reaction becomes complicated when it is performed in nitric acid medium. When the molarity of HNO₃ is higher than 1.0 mol/L, nitrous acid will be produced via the reaction between nitric acid and DMHAN. The reaction products are analyzed and the reaction mechanism is discussed in this paper.     

Si-Containing Amides of Phosphoric Acid

The first representative of the N-silylmethylamides of phosphoric acid O=P[NMe(CH₂SiMe _n (OEt)_3-n ]₃ have been synthesized by interaction of MeNHCH₂SiMe _n (OEt)_3-n (n = 2, 3) with POCl₃. The interaction of the N,N′,N″-trimethyl-N,N′,N″-tris[(ethoxydimethyl- silyl)methyl]triamide phosphoric acid with BF₃·Et₂O or BCl₃ results in the formation of the N,N′,N″-trimethyl-N,N′,N″-tris[(fluorodimethyl-silyl)methyl]triamide phosphoric acid or N,N′,N″-trimethyl-N,N′,N″-tris[(chlorodimethylsilyl)methyl]triamide phosphoric acid. NMR data show on the tetracoordinate state of silicon in these products.     

Reactions of <Emphasis Type="Italic">N</Emphasis>-acetyltrifluoroacetamide with chlorophosphites

Reactions of N-acetyltrifluoroacetamide with chlorophosphites give rise to O-phosphorylated N-trifluoroacetoacetylimidates, which transform into α-phosphorylated vinylamides of trifluroacetic acid as a result of vinylphosphite-vinylphosphonate rearrangement. On the basis of nonempirical calculations data the reaction protocol of N-acetyltrifluoroacetamide with chlorophosphites was suggested.     

Synthesis, Crystal Structure and Properties of Polyamine Copper(II) Complexes

Two polyamine copper(II) complexes were synthesized by the reaction between N,N,N′,N′-tetrakis(2′-aminoethyl)propane-1,2-diamine hexahydrochloride and copper(II) perchlorate under almost the same conditions except for reaction temperature. The crystal structures of two complexes were determined by X-ray diffraction techniques, which shows that one of the complexes is unexpected and is a double chlorine or chloride-bridged dinuclear copper(II) complex formed by two diethylenetriamines, and another is a pentadentate mononuclear copper(II) complex composed of homo-protonated N,N,N′,N′-tetrakis(2′-aminoethyl)propane-1,2-diamine. The mechanism of the reaction leading to form the unexpected complex was discussed. The UV-visible spectra and cyclic voltammogram of the complexes were measured.     

Si-Containing Amides of Phosphoric Acid

Summary. The first representative of the N-silylmethylamides of phosphoric acid O=P[NMe(CH₂SiMe _n (OEt)_3-n ]₃ have been synthesized by interaction of MeNHCH₂SiMe _n (OEt)_3-n (n = 2, 3) with POCl₃. The interaction of the N,N′,N″-trimethyl-N,N′,N″-tris[(ethoxydimethyl- silyl)methyl]triamide phosphoric acid with BF₃·Et₂O or BCl₃ results in the formation of the N,N′,N″-trimethyl-N,N′,N″-tris[(fluorodimethyl-silyl)methyl]triamide phosphoric acid or N,N′,N″-trimethyl-N,N′,N″-tris[(chlorodimethylsilyl)methyl]triamide phosphoric acid. NMR data show on the tetracoordinate state of silicon in these products. Professor Vadim Aleksandrovich Pestunovich, our chief, teacher and friend died on July 4^th, 2004