Facile direct synthesis of unsymmetrical ureas from N-Alloc-, N-Cbz-, and N-Boc-protected amines using DABAL-Me3

A practical synthetic method for the direct synthesis of unsymmetrically substituted ureas from N-Alloc-, N-Cbz-, and N-Boc-protected amines is described. In this study, efficient direct conversion of the Alloc-, Cbz-, and Boc-carbamate compounds to ureas was achieved in the presence of DABAL-Me₃, an air stable and easily handled reagent. Using this reaction method, both protected aromatic and aliphatic amines were successfully transformed into various trisubstituted and tetrasubstituted ureas with high yields without side product. Our findings offer promising guidelines for direct preparation of useful ureas from N-Alloc-, N-Cbz-, and N-Boc-carbamates.     

N-substituted imines of methyl trif luoropyruvate in the synthesis of 5-amino-5-trifluoromethylhydantoins

Cyclocondensation of N-substituted imines of methyl trifluoropyruvate with monosubstituted ureas afforded novel 5-amino-5-trifluoromethylhydantoins. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1014–1017, June, 2006.     

Study of alkaloids of the Siberian and Altai flora. 10. Synthesis of N(20)-deethyllappaconitine derivatives

Efficient procedures were developed for N-deethylation of lappaconitine to give N(20)-deethyllappaconitine. Alkyl derivatives of N(20)-deethyllappaconitine, including labeled lappaconitine, and N(20)-acetoxy-N(20)-deethyllappaconitine were prepared for the first time. The assignments of the signals for the carbon atoms in the ¹³C NMR spectra of lappaconitine and related lappaconine were refined using ¹³C—¹³C 2D INADEQUATE and 2D ¹³C—¹H correlation experiments.     

Reactions of hexaorganyldigermoxanes with O-trimethylsilyl carbamates

Hexa-n-butyl- and hexaisopentyldigermoxanes but not hexaphenyldigermoxane react with O-trimethylsilyl N,N-diethylcarbamate and trimethylsilyl piperidinocarboxylate to give O-triorganylgermyl carbamates.     

Synthesis of N-trinitroethyl derivatives of linear and heterocyclic nitrogen-containing compounds

Earlier unknown N-trinitroethyl derivatives of acetylhydrazine, 4-amino-1,2,4-triazole, and 2,4,6-triamino-1,3,5-triazine, which are potential components for gas-generating formulations, were synthesized. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1306–1309, May, 2005.     

Synthesis of alkoxystannanes by reactions of O-(organylstannyl) carbamates with alcohols

Reactions of O-(organylstannyl) carbamates with alcohols afford alkoxystannanes and proceed most completely on heating in an excess of alcohol. The reactions provide a new approach to the synthesis of difficultly accessible alkoxystannanes.     

Synthesis of N-haloacyl and N-hetarylthioacyl derivatives of 2-amino-5-aryl-6H-1,3,4-thiadiazine

Conditions for N-acylation of 2-amino-5-aryl-6H-1,3,4-thiadiazines with trifluoroacetic anhydride and halogen-substituted carboxylic acid halides with retention of the initial heterocyclic system were found. 5-Aryl-2-haloacylamino-6H-1,3,4-thiadiazines were obtained in preparative yields. Their reactions with hetarenethiols afforded N-hetarylthioacyl derivatives. Dedicated to Academician V. A. Tartakovsky on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1570–1575, August, 2007.     

A convenient synthesis of 3,3,3-trifluoroalanine derivatives

A one-pot synthesis of N-substituted 3,3,3-trifluoroalanine esters from alkyl trifluoropyruvates and carboxamides or substituted ureas was developed.     

Extraction and spectrophotometric determination of titanium(IV) withN 1-hydroxy-N 1,N 2-diphenylbenzamidine and thiocyanate

A precise, reliable, sensitive, and selective method for the determination of titanium(IV) is described. Titanium(IV) reacts withN ¹-hydroxy-N ¹,N ²-diphenylbenzamidine (HDPBA) and thiocyanate to form an orange-coloured mixed-ligand complex of stoichiometry 112 (Ti SCN^– HDPBA). The complex is quantitatively extractable into toluene from 0.05–0.15M hydrochloric acid. The spectrum of the complex exhibits an absorption maximum at 400 nm with a molar absorptivity of 20000M ^–1 cm^–1 and the coloured system obeys Beer's law in the concentration range 0.20–3.0 gml^–1 titanium. The effects of foreign ions and of various experimental parameters have been studied to establish the optimum conditions for the extraction and determination of titanium. The precision of the method has been evaluated and the relative standard deviation has been found to be 0.53%. The method has been successfully applied to the determination of titanium in synthetic matrices corresponding to titanium-containing ores, minerals, and alloys.     

Synthesis of 5,6-indolo-12-crown-4 ethers

o-Alkyl derivatives of N-acetylaminobenzo-12-crowns-4 4a—f were prepared by Pd—Cu-catalyzed alkynylation of 5"-N-acetylamino-4"-iodobenzo-12-crown-4 (2). Cyclization of compounds 4a—f afforded the corresponding substituted 5,6-indolo-12-crowns-4 5a—c.     

A facile and one-pot synthesis of N-Fmoc/Bsmoc/Boc/Z-protected ureidopeptides and peptidyl ureas employing diphenylphosphoryl azide [DPPA]

Diphenylphosphoryl azide (DPPA) mediated one-pot synthesis of N^α-Fmoc/Bsmoc/Boc/Z-protected ureidopeptides and peptidyl ureas as well as phenyl/succinimidyl (N^α-urethane protected) methyl carbamates starting from N^α-protected amino acids is reported. The formation of an azide, its rearrangement and coupling with an amino component is accomplished in a sequence of one-pot operations. The protocol has incorporated urea linkages in a sterically hindered peptide.     

Interaction of cellulose with amine oxide solvents

Cellulose I, mainly as ramie or as Avicel microcrystalline cellulose, has been monitored by optical microscopy and by ¹³C CPMAS NMR, over the course of its dissolution in hot N-methylmorpholine N-oxide solvent. Its interaction with the near-solvent N-ethylmorpholine N-oxide and related non-solvents has also been investigated. NMR shows that N-methylmorpholine N-oxide partly converts crystalline cellulose I into amorphous solid cellulose. The changes in chemical shift imply increased flexibility at the glycosidic bonds. In contrast, N-ethylmorpholine N-oxide converts cellulose I to cellulose III_I, without dissolution. Microscopy shows that the ramie fibres swell laterally, and at least some also shorten longitudinally, during dissolution. Model studies using methyl--d-glucopyranose show no evidence from ¹³C chemical shifts for different modes of binding with different solvents. However, N-methylmorpholine N-oxide binds more strongly to methyl--d-glucopyranose in DMSO than does N-ethylmorpholine N-oxide, whereas N-ethylmorpholine N-oxide binds better to H₂O. Also, ¹³C T ₁ values for aqueous cellobioside show increasing rotational freedom of the –CH₂OH sidechains as N-methylmorpholine N-oxide is added. Together, these observations imply the initial penetration of solvents and near-solvents between the molecular cellulose sheets. Subsequently, N-methylmorpholine N-oxide breaks H-bonds, particularly to O-6, just sufficiently to loosen individual chains and then dissolve the sheets.     

1,2,4-Triazino[5,6,1-i,j]quinolines: a new type of tricyclic analogs of fluoroquinolones

The interaction of C-aryl-substituted amidrazones and S-methylisothiosemicarbazide with 3-ethoxy-2-polyfluorobenzoylacrylates results in corresponding N-(quinolin-1-yl)amidines that undergo conversion into derivatives of 1,2,4-triazino[5,6,1-i,j]quinoline by heating in acetic anhydride.     

Syntheses based on anabasine. Preparation and transformations of N-oxides

The oxidation of N-acetyl-and N-benzoylanabasine with the tert-butyl hydroperoxide (TBHP)— MoCl₅ system or MCPBA proceeds selectively at the nitrogen atom of the pyridine ring. The oxidation of N-methylanabasine under similar conditions gives a mixture of stereo-isomeric N-oxides at the piperidine nitrogen atom, their ratio depending on the reagent used. The oxidation of anabasine by TBHP— MoCl₅ or MCPBA is accompanied by dehydrogenation and results in anabaseine N-oxide. The reactions of anabasine and anabaseine pyridine N-oxides with acetic anhydride were investigated. The substituted 1H-3-pyridin-2-ones were prepared. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 322—328, February, 2006.     

An Efficient Method for the Synthesis of N-Acylsulfonamides: One-pot Sulfonylation and Acylation of Primary Arylamines under Solvent-Free Conditions

Summary. The preparation of N-acylsulfonamides is described using primary amines, arylsulfonyl chlorides and acyl chlorides. Reaction of primary aryl amines with arylsulfonyl chlorides in the presence of NaHCO₃ produced N-arylsulfonamides, which reacted in situ with benzoyl chloride furnishing the corresponding N-benzoyl-N-arylsulfonamides in 72–96% yields. Accordingly, 4-nitrobenzoyl chloride and 3,5-dinitrobenzoyl chloride were used as acylating agents. All the reactions were carried out under solvent-free conditions at room temperature and the products were isolated after simple work-up in high yields and purity.     

Hexafluoroacetone as Protecting and Activating Reagent. A New Approach to <Emphasis Type="Italic">N</Emphasis>-Glycosides

Summary. N-Glycosides of Asn and homologues have been synthesized starting from hexafluoroacetone-protected -activated Asp, Glu, and Aad derivatives and glycosylamines. The synthetic value of the new building blocks was demonstrated by the concise incorporation of N-glycosylated Asn, Gln, and Aad -amides into glycopeptides.     

Quantitative 2H NMR spectroscopy. 1. Thermodynamic H/D isotope effects in N,N-dimethylformamide and cyclopentadiene molecules

A new method for quantification of the relative distribution of deuterium in molecules is proposed. The technique is based on the lineshape analysis in the ²H NMR spectra obtained at the natural abundance level of deuterium with allowance for inhomogeneity of the magnetic field. The equilibrium thermodynamic H/D isotope effects for hindered rotation about the C—N bond in the N,N-dimethylformamide molecule and for prototropic exchange in the cyclopentadiene molecule were determined. The results obtained agree with those of DFT calculations of the vibrational energies.     

Thermal transformation of cyclopropylazoarenes into the five-membered nitrogen-containing heterocycles

Cyclopropylazoarenes containing methoxy groups in the aromatic ring give the corresponding N-arylpyrazolines on the reflux in o-dichlorobenzene or on SnCl₂ catalysis at 80 °C in good yields. The products can be smoothly oxidized into the corresponding pyrazoles. Thermolysis of cyclopropylazoarenes containing hydroxy groups in the aromatic ring proceeds more complicated. Thus in the case of resorcin azo derivative, strong resinification of the reaction mixture is observed and the corresponding N-arylpyrazoline is isolated only in −40% yield. Under similar conditions, thermolysis of 1-cyclopropyl- and 1-(1-methylcyclopropyl)azo-2-naphthol proceeds otherwise and unexpectedly leads to naphtho[1,2-d]oxazole derivatives with degradation of the cyclopropane ring. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1686–1692, August, 2008.     

Determination of 13C isotopic enrichment of valine and threonine by GC-C-IRMS after formation of the N(O,S)-ethoxycarbonyl ethyl ester derivatives of the amino acids

We describe a new method of assessing, in a single run, ¹³C isotopic enrichment of both Val and Thr by gas chromatography–combustion–isotope-ratio mass spectrometry (GC–C–IRMS). This method characterised by a rapid one-step derivatisation procedure performed at room temperature to form the N(O,S)-ethoxycarbonyl ethyl ester derivatives, and a polar column for GC. The suitability of this method for Val and Thr in in-vivo samples (mucosal hydrolysate) was demonstrated by studying protein metabolism with two tracers (¹³C-valine or ¹³C-threonine). The intra-day and inter-day repeatability were both assessed either with standards or with in-vivo samples at natural abundance and at low ¹³C isotopic enrichment. For inter-day repeatability CVs were between 0.8 and 1.5% at natural abundance and lower than 5.5% at 0.112 and 0.190 atom% enrichment for Val and Thr, respectively. Overall isotopic precision was studied for eleven standard amino acid derivatives (those of Val, Ala, Leu, Iso, Gly, Pro, Asp, Thr, Ser, Met, and Phe) and was assessed at 0.32‰. The ¹³C isotopic measurement was then extended to the other amino acids (Ala, Val, Leu, Iso, Gly, Pro, Thr, and Phe) at natural abundance for in-vivo samples. The isotopic precision was better than 0.002 atom% per amino acid (for n = 4 rats). This analytical method was finally applied to an animal study to measure Thr utilization in protein synthesis.