Presence of an N-6 acetate group shifts the alkylation site of the ambident nucleophile sodium 1-N-methylisoguanide

Inclusion of an N-6 acetate into the ambident nucleophile, sodium 1-N-methylisoguanide, resulted in a shift in alkylation preference from N-9 to N-3. The preparation of the N-6 acetate of 1-N-methylisoguanine, 9-N-acetyl-1-N-methylisoguanine (4) , and related acetate analogs are described and evidence presented for their structural determination. Analysis of long range ¹³C-¹H coupling data facilitated the structural elucidation of the predominant alkylation products and provided evidence for the unusual N-7 hydrogen tautomeric form in one of them, 3-N-benzyl-6-N-acetyl-1-N-methylisoguanine (8).     

Synthesis of 1,3,4-thiadiazoles containing the trifluoromethyl group

The following compounds have been synthesized: 2-Amino-5-trifluoromethyl-1,3,4-thiadiazole; N-(5-trifluoromethyl - 1,3,4-thiadizol-2-yl)benzenesulfonamide; N¹-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)sulfanilamide, its N⁴-acetyl, N⁴-succinyl, and N⁴-pathalyl derivatives; o - m - and p-trifluoromethylbenzoylthiosemicarbazide, their corresponding 2-amino-1,3,4-thiadiazoles, their corresponding sulfanilamides, their N⁴-acetyl, N⁴-succinyl and N⁴-phthalyl derivatives; 3-o-trifluoromethylphenyl-4H-1,2,4-triazole-5-thiol. Preliminary in-vitro assays show that synthesized sulfanilamide derivatives have antibacterial activity against Staphylococcus aureus.     

Studies on the Fast Atom Bombardment Mass Spectrometry Fragmentation of Amino Sugars Using Synthetic Derivatives of the Trisaccharide Unit β-D-Glucopyranosyl-(1-3)-O-2-deoxy-2-amino-β-d-glucopyranosyl-(1-4)-O-d-glucopyranose

Abstract

N-Phthaloyl, N-acetyl, N-benzyl, N-acetyl-N-methyl, N,N-dimethyl, N-benzoyl, and N,N-dibenzoyl derivatives of the trisaccharide β-D-glucopyranosyl-(1-3)-O-(2-deoxy-2-amino-β-D-glucopyranosyl)-(1-4)-O-β-D-glucopyranose were synthesized and analyzed by FAB MS. The intensity ratios of the peaks resulting from cleavage of the anomeric bond of the glucosamine residue and the respective molecular ion peaks turned out to be high for the N-acyl derivatives and up to two orders of magnitude lower for the N-alkyl compounds. These results show that fragmentation at the anomeric carbon of the amino sugar may be assisted by the carbonyl group and the resulting cation is stabilized by delocalization of the positive charge.     

Studies on the syntheses of azole derivatives. Part IX. Formation of 2,4-disubstituted δ2 -1,3,4-oxadiazolin-5-one and 4-substituted 1,2,4-triazolidin-3,5-dione derivatives by thermal reaetion of N-aryl-N-benzylearbamoyl azides

The structure of the novel produets, 2,4-ltis-(N-benzy1-4-nitroanilino)-Δ²-1,3,4-oxadiazolin-5-one (VII), 2-benzy1-1-(N-benzy1-4-chloroanilino)-4-(4-chlorophenyl)-1,2,4-triazolidin-3,5-dione (XIVa), and 2-benzy1-1-(N-benzylanilino)-4-pheny1-1,2,4-triazolidin-3,5-dione (XIVb), obtained upon thermal reaction of N-bcnzyl-N-(4-nitrophenyl)carbamoyl azide (la), N-benzyl-N-(4-chloro-phenyl)carbamoyl azide (Ib) and N-benzyl-N-phcnylcarbamoyl azide (le), respectively, were determined.     

Application of the ortho-lithiation-cyclization strategy to N-benzyl-and N-phenethylamine derivatives

The ortho-lithiation-cyclization of iodinated N,N-diacylphenethylamines provides a convenient method for the preparation of 2-(2-acetoamidoethyl)acetophenones and 2-(2-benzamidoethyl)benzophenones, which could be easily transformed into dihydroisoquinolines. By contrast, the N-ethylamino, N-acetylamino, and N-trimethylsilylamino moieties studied as ortho-directing groups provide poor assistance to the metalation of N-benzyl- and N-phenemylamines and the corresponding isoindolone or isoquinolone derivatives are obtained in low yields.     

Investigations of Steric and Electronic Factors Influencing the Cyclopalladation of meta-Toluidine Analogues

The cyclopalladation of two different types of aniline derivatives is described: the acetylated anilines N-(3-methylphenyl)acetamide ( 2a ), 3-(acetylamino)-4-chlorobenzoic acid ( 2c ), and N-(2-chlorophenyl)acetamide ( 2d ) are cyclometalated easily with palladium(II) acetate and trifluoroacetic acid to yield the corresponding complexes 4a, 4c , and 4d , respectively, whereas the acetylated meta-toluidine N-(2-chloro-5-methylphenyl)acetamide ( 2b ) cannot be metalated at the only accessible site between the acetylamino and the methyl group. This aromatic C? H bond can be activated, however, with the second type of meta-toluidine derivatives: the 2-chloro-5, N-dimethyl-N-nitrosoaniline ( 3b ) readily undergoes cyclopalladation to yield the corresponding Pd^II complex di-μ-trifluoro-acetato-bis[3-chloro-6-methyl-2-(N-methyl-N- nitrosoamino)phenyl-C,N? O]dipalladium(II) ( 5b ) containing a five-membered palladacycle with coordination of Pd^II at the nitroso N-atom, which is established by ¹⁵N-NMR spectroscopy.     

NMR studies in the heterocyclic series. XX—a carbon-13 NMR study of the structures of N-hydroxybenzotriazole and its acylated derivatives

Assignment of the carbon resonances in nine derivatives of N-hydroxybenzotriazole has been carried out. The ¹³C NMR method enables tautomeric N-hydroxy and N-oxide and isomeric O- and N-acyl structures to be identified. In DMSO, the predominant tautomer of N-hydroxybenzotriazole was found to be the N-hydroxy form. The structure of the benzoate and methyl and phenyl carbonate esters were likewise established, but for the two latter compounds, hydrolysis of the equilibrating O- and N-acyl isomers imposed some limitations on the usefulness of the technique.     

Thermochemical study of the trans- and cis-isomeric forms of 4-(4-methoxystyryl)pyridine N-oxide

The trans and cis form of 4-(4-methoxystyryl)pyridine N-oxide were studied. The spectral characteristics of cis-4-(4-methoxystyryl)pyridine N-oxide were determined in acetonitrile. The melting and thermal decomposition processes of the trans and cisforms of 4-(4-methoxystyryl)pyridine N-oxide were studied by thermochemical methods. It was establish that the thermal decomposition of 4-(4-methoxystyryl)pyridine N-oxide begins with the cleavage of the bond between the pyridine and benzene rings.

     

Three-component condensation in the synthesis of substituted tetrahydropyridinethiolates

Multicomponent cyclocondensation of Meldrum's acid, 2-chlorobenzaldehyde, and N-(4-bromophenyl)-3-amino-3-thioxopropanamide in the presence of N-methylmorpholine afforded N-methylmorpholinium 3-[N-(4-bromophenyl)carbamoyl]-4-(2-chlorophenyl)-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolate in 65% yield. When treated with dilute HCl, the thiolate easily transformed into N-(4-bromophenyl)-4-(2-chlorophenyl)-2-oxo-6-thioxopiperidine-5-carboxamide, which reacted with alkyl halides to give products of regioselective S-alkylation in high yields. 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. 1297–1298, May, 2005.     

Synthesis, X-Ray Diffraction Data, and 1H and 13C NMR Spectra of N-(N-Arylsulfonylimidoyl)-1,4-benzoquinonimines Derived from N-Aroyl(acetyl)-1,4-benzoquinonimines

Oxidation of N-(N-arylsulfonylimidoyl)-4-aminophenols gave the corresponding N-[N-arylsulfonylimidoyl)-1,4-benzoquinonimines, derivatives of N-aroyl- and N-acetyl-1,4-benzoquinonimines. The structure of the products was studied by the X-ray diffraction method and ¹H and ¹³C NMR spectroscopy. N-(N-Arylsulfonylimidoyl)-1,4-benzoquinonimines were found to undergo fast (on the NMR time scale) Z E isomerization about the CÍN bond in the quinonimine fragment. N-(N-Arylsulfonylacetimidoyl)-1,4-benzoquinonimines in solution give rise to dynamic Z E-isomerization with respect to the CÍN bond in the N-arylsulfonylacetimidoyl fragment.     

Syntheses of N-substituted carbazoles involving polymerizable terminal vinyl groups

Eleven N-substituted carbazoles (CZ) with terminal vinyl groups were synthesized by five sequences of reaction: N-(p-vinylbenzyl)- and N-β-(vinyloxyethyl)CZ by N-alkylations of potassium CZ with corresponding chlorides; N-(β-acryloyloxyethyl)CZ by the esterification of N-(β-hydroxyethyl)CZ with acryloyl chloride; N-acrylamido-or methacryl-amido-methyl CZ from N-hydroxymethyl CZ and acryl- or methacrylamide; N-(3-acryloyl- or methacryloyl-oxy-2-hydroxypropyl)CZ and N-[3-(p- or m-vinylanilino)-2-hydroxypropyl] CZ from N-(2,3-epoxypropyl)CZ and acrylic or methacrylic acid and p- or m-vinylaniline, respectively; and 2-[β-(N-carbazyl)propionyloxy]ethyl acrylate or methacrylate by the Michael addition of CZ to 2-hydroxyethyl acrylate or methacrylate, followed by esterifications. The vinyl polymers with pendant carbazyl groups more or less distant from the polymer backbones, prepared by conventional radical or cationic polymerization procedures, indicated charge-transfer spectra with 2,4,7-trinitrofluorenone (TNF) in tetrahydrofuran (THF) solutions that are spread over most of the visible range.     

Kinetics and mechanism of the decomposition of N,N-dihalopeptides

The tripeptide alanylalanylalanine reacts with either HOCl or HOBr to form a N,N-dihalopeptide. These compounds decompose to the N-halo-N′-(α-iminoketo)peptides plus halide ion. The rate constants for these reactions in 0.4-M NaCl were determined to be where the activation energies are in cal/mol. The N-halo-N′-(α-iminoketo)-peptides slowly decompose either by a two-step hydrolysis reaction to form ammonia, halide ion, and an N-(α-acylketo)peptide, or by direct decomposition to a nitrile, an isocyanopeptide, and a halide ion.     

Studies on the hydrolysis of cyclophosphamide II. Isolation and characterization of intermediate hydrolytic products

Two new products of hydrolysis of cyclophosphamide in water at 100°, N-(2-chloroethyl)-N' -(3-phosphatopropy l)ethylenediamine and N-(2-hydroxyethyl)-N -(3-phosphatopropyl)ethylene-diamine, have been isolated after 30 minutes, and 6 hours of reaction times, respectively. These products have been shown to be intermediates leading to the formation of N-(2-hydroxyethyl)-N'-(3-hydroxypropyl)ethylenediamine, the principal ultimate product of cyclophosphamide hydrolysis. The nature of these new products supports the previously postulated mechanism involving an intramolecular alkylation as the initial step in the hydrolytic process although the pathway appears to be an unlikely model for the metabolic transformations of cyclophosphamide in vivo.     

Quantum chemical study of the transformation of 2-(N-alkylamino)-3-(indol-1-yl)-and 2-(N-alkylamino)-3-(indol-3-yl)maleimides by protic acids: Tandem hydride transfer/cyclization mechanism

The geometric parameters, the charge distribution, and the energetics of N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)-and N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimides and their conjugated acids were studied by density functional theory calculations at the B3LYP/6-31G(d) level. The mechanism of the tandem hydride transfer/cyclization sequence, which occurs after protonation of N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)-and N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimides, was analyzed. The investigation of the potential energy surface for the tandem hydride transfer/cyclization of the iminium cation that formed upon protonation revealed that the hydride transfer followed by intramolecular cyclization at position 7 of the indole fragment in N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)maleimide is the preferable process, unlike alternative intramolecular cyclization involving the cationic center at the C(2) atom of the indole fragment and the benzene ring of the N-ethylaniline fragment of the indoleninium cation in N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimide. A study of the key intermediates of the assumed reaction mechanism demonstrated that these intermediates are actually stationary points on the potential energy surface (minima and transition states). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2069–2073, December, 2006.     

Synthesis of versatile intermediates of the ferrocene series: reductive amination of ferrocenecarbaldehyde

Reductive amination of ferrocenecarbaldehyde with several primary and secondary amines in the presence of sodium triacetoxyborohydride was studied. This method was used for the synthesis of new ferrocenylmethylamines, viz., N-(ferrocenylmethyl)isoleucine methyl ester, N,N-bis(ferrocenylmethyl)glycine ethyl ester, and N-(3,5-dibenzyloxybenzyl)-N-(ferrocenylmethyl)methylamine. The latter is a potential precursor of a dendrimer with the chiral ferrocenyl plane in the core.     

Synthesis of isonipecotinoyl analogues of aminopterin and folic acid

The preparation of isonipecotinoyl analogues of aminopterin and methotrexate is described. Condensation of diethyl N-isonipecotinoyl-L-glutamate 4 with 2-amino-5-bromomethyl-3-cyanopyrazine 5 afforded diethyl N-(N-[(2-amino-3-cyanopyrazin-5-yl)methyl]isonipecotinoyl)-L-glutamate 6 . Cyclisation of 6 with guanidine followed by blocking group hydrolysis afforded N-([N-(2,4-diaminopteridin-6-yl)methyl]isonipecotinoyl)-L-glutamic acid 8 . Coupling of N-(2-amino-4(3H)ioxopteridin-6-yl]methyl)isonipecotinic acid 11 with diethyl L-glutamate gave diethyl N-[(N-[2-amino-4(3H)-oxopteridin-6-yl]methyl)isonipecotinoyl]-L-glutamate 12 . Blocking group hydrolysis afforded N-[(N-[2-amino-4(3H)-oxopteridin-6-yl]methyl)isonipecotinoyl]-L-glutamic acid 13 .     

The photochemical reactions of the halogenated N-benzylanilines. Mechanism of the reactions

Several N-(2-halobenzyl)anilines and N-benzyl-2-haloanilines have been synthesized and their photochemical reactions studied. Upon irradiation, the aqueous acetonitrile solution of N-benzyl-2-chloroaniline was cyclized and reduced to give phenanthridine, 5,5′,6,6′-tetrahydro-6,6′-biphenanthridyl (THBP), N-ben-zylaniline, and bibenzyl. Similar products were produced in the photochemical reactions of other halo-genated N-benzylanilines, except iodo-substituted N-benzylanilines. No dimer (THBP) was produced from the iodo-substituted N-benzylanilines. Both singlet and triplet states are involved in the photochemical reactions of the haloarenes.     

A new methodology of annelation of five- and seven-membered heterocycles to quinoxalines

Pyrazolo[3,4-b]-, isoxazolo[4,5-b]-, benzo[2,3]-1,4-diazepino-, and benzo[2,3]-1,4-oxazepinoquinoxalines were prepared by reactions of 2-quinoxalinecarboxaldehyde with 1,2-N,N-, 1,2-N,O and 1,4-N,N- and 1,4-N,O-dinucleophiles.     

Studies on the syntheses of azole derivatives. Part VIII. Photolysis of N-aryl-N-benzylearbamoyl azides [studies on the syntheses of heterocyclic compounds. Part CDXV

Photolysis of N-benzyl-N-phenylearbamoylazide (IVc) afforded 1-benzy 1-2-benzimidazolinone (Ic), 2-benzimidazolinone (IIe), 4-benzy 1-2-benzimidazolinone (IIe), and 5-benzy1-2-benzimidazo-linone (IIf)- The same reaction of N-benzyl-N-(4-chlorophenyl) carbamoyl azide (IVd) gave 3-benzyl-1-(phenylhydrazocarbonyl)-2-benzimidazolinone (VIb) besides the above four products. In the case of N-benzyl-4-(4-butoxyphenyl)carbamoyl azide (IVe), 1-benzy1-5-butoxy-2-benz-imidazolinone (1e), 5-butoxy-2-benzimidazolinone (IId), 5-benzy1-2-benzimidazolinone (IIf), and 4-benzy1-6-butoxy-2-benzimidazolinone (IIg).     

Studies in tertiary amine oxides. Part V—carbon-13 nuclear magnetic resonance spectra of some N-aryl tertiary amines,the corresponding N-oxides and the meisenheimer rearrangement products

The carbon-13 NMR spectra of some N-(2- or 4-nitrophenyl) tertiary amines and their corresponding N-oxides have been analysed. These N-oxides undergo thermal rearrangement to O-arylhydroxylamines, for which the ¹³C NMR spectral assignments were also carried out. The N-oxidation effect on the aromatic and aliphatic fragments is calculated.