Nitrogen and carbon NMR of some benzofuroxans

¹⁵N and ¹⁴N NMR spectra show that there is no valence tautomerism involving the nitro group in nitro derivatives of benzofuroxan systems and that the N-oxide function has a fixed position in the furoxan ring. Carbon chemical shifts of molecules with one, two or three furoxan rings attached to a benzene ring reveal additivity of effects which makes possible a complete and unambiguous assignment of the shifts.     

Synthesis,structural and conformational study of some esters derived from 8-phenethyl-8-azabicyclo[4.3.1]decan-10α-ol

A series of 10α-acyloxy-N-phenethyl-8-azabicyclo[4.3.1]decane derivatives have been synthesized and studied by ¹H and ¹³C nmr spectroscopy, and the crystal structure of N-phenethyl-10aL-(xanten-9″-carbonyloxy)bicyclo[4.3.1]decane 2 has been determined by X-ray diffraction. The compounds studied display in deuteriochloroform the same preferred conformation adopted by the piperidine ring as a distorted chair conformation flattened at N-8 with both the phenethyl and acyloxy groups in the equatorial position with respect to the piperidine ring. These results are in close agreement with that found for compound 2 in the crystalline state.     

Synthesis,structural and conformational study of N-β(or γ)-acyloxyalkylnortropinones

A series of N-β(γ)-acyloxyalkylnortropinones have been synthesized and studied by ¹H and ¹³C nmr spectroscopy, and the crystal structure of N-[γ-(p-chlorophenylcarbonyloxy)propyl]nortropinone 4 has been determined by X-ray diffraction. The compounds studied display in deuteriochloroform solution the same preferred conformation. The pyrrolidine and piperidone rings adopt a flattened N-8 envelope and distorted chair conformation, puckered at N-8 and flattened at C-3 respectively, with the N-substituent in axial position with respect to the piperidone ring. These results are in close agreement with that found for compound 4 in the crystalline state.     

Determination of the preferred tautomeric form of 4-nitrohistidine

Spectrophotometric pKa determinations of methyl derivatives of N^α-acetyl-4-nitrohistidine methyl ester 1 have been used to determine the position of the tautomeric equilibrium of 1 . The N₁-H tautomer is the predominant form with an equilibrium constant K_T of 48. The conclusion is supported qualitatively by the study of ¹H-nmr and ¹³C-nmr chemical shifts of the imidazole ring atoms and their changes from neutral to acidic media.     

Stereochemical studies—XXXVII: Saturated heterocycles—XIII Configuration and conformation of Z- and E-N-methyl- and -N- benzyl-2-p-nitrophenyl-4,5- and -5,6-tetramethylenetetrahydro-1,3-oxazines

The configuration and conformation of Z- and E-N-methyl- and -N-benzyl-2-p-nitrophenyl-4,5-, and -5,6-tetramethylenetetrahydro-1,3-oxazines were determined by ¹H and ¹³C NMR spectroscopy. The Z isomers were proved to be conformationally homogeneous, having the heteroatom in axial and equatorial position, respectively, in the case of the 5,6- and 4,5-tetramethylene compounds. Consequently, the p-nitrophenyl group and the anellated cyclohexyl ring are all-cis arranged in the Z-5,6-tetramethylene compounds while in the case of the Z-4,5-tetramethylene isomers the p-nitrophenyl group and the cyclohexyl ring are trans arranged to the hetero ring.     

Preferential protonation and methylation at the nitrogen atoms of N,N-dimethylamino derivatives of pyridine

The relative reactivity toward protonation and methylation of the two nitrogen atoms in N,N-dimethylaminopyridines has been examined by ¹H NMR. The ring position of the dimethylamino group has no influence on protonation, which occurs in all the derivatives at the heterocyclic nitrogen. The N-methylation reaction does not follow a homogeneous behaviour, occurring at the exocyclic nitrogen in the 2-substituted dimethylamino derivative. The electronic characteristics of the molecules, determined by MO calculations at a semi-empirical level, indicate that both protonation and methylation should occur at the heterocyclic nitrogen; the calculated relative stabilites, however, of the N-protonated and N-methylated forms are in full agreement with the experimental results, and it appears that the anomalous behaviour of 2-dimethylaminopyridine in the N-methylation reaction is caused by steric factors.     

Change of the favored routes of EI MS fragmentation when proceeding from N1, N1‐dimethyl‐N2‐arylformamidines to 1,1,3,3‐tetraalkyl‐2‐arylguanidines: substituent effects

Although series of N¹, N¹‐dimethyl‐N²‐arylformamidines and of 1,1,3,3‐tetraalkyl‐2‐arylguanidines are structurally analogous and similar electron‐ionization mass spectral fragmentation may be expected, they display important differences in the favored routes of fragmentation and consequently in substituent effects on ion abundances. In the case of formamidines, the cyclization‐elimination process (initiated by nucleophilic attack of the N‐amino atom on the 2‐position of the phenyl ring) and formation of the cyclic benzimidazolium [M‐H]⁺ ions dominates, whereas the loss of the NR₂ group is more favored for guanidines. In order to gain information on the most probable structures of the principal fragments, quantum‐chemical calculations were performed on a selected set. A good linear relation between log{I[M‐H]⁺I [M]^+?} and σ_R⁺ constants of substituent at para position in the phenyl ring occurs solely for formamidines (r = 0.989). In the case of guanidines, this relation is not significant (r = 0.659). A good linear relation is found between log{I[M‐NMe₂]⁺/I [M]^+?} and σ_p⁺ constants (r = 0.993). Copyright © 2010 John Wiley & Sons, Ltd.     

Reactions of 6-Alkoxy(alkylthio)carbonylamino-4-hydroxy-2H-pyran-2-ones with Some Electrophilic Reagents

Alkoxy(alkylthio)-4-hydroxy-2H-pyran-2-ones readily react with electrophiles to give substitution products at C³. Hard electrophilic reagents replace hydrogen both in position 3 and in position 5 of the pyran ring. Methylation of 6-alkoxy(alkylthio)-4-hydroxy-2H-pyran-2-ones with diazomethane leads to formation of O- and N-methyl derivatives.     

Conformational preferences of 6-furfuryl amino purine and 6-benzyl amino purine

Conformational preferences of N⁶-furfurylamino purine (kinetin) and N⁶-benzyl amino purine (BAP ) have been investigated theoretically by the quantum chemical perturbative configuration interaction using localized orbitals method. The predicted most stable conformations for these molecules are quite similar. The N⁶ substituents in both these molecules are oriented toward N(1) and away from the imidazole moiety of the purine. The furfuryl ring in kinetin as well as the aromatic benzene ring in BAP are not coplanar with the purine ring. Comparison of these results with the preferred conformation of another compound N⁶-(Δ²-isopentenyl) adenine reveals striking similarity in the orientations of the N⁶ substituents in these cytokinin-active plant-growth-stimulating substances.     

Synthesis of Glucose‐Containing Polyaniline by the Oxidative Polymerization of N‐Glucosylaniline

Summary: The oxidative polymerization of N‐glucosylaniline was carried out using ammonium persulfate as the oxidant in phosphate buffer. The structure of the isolated polymer was determined by ¹H NMR, ¹³C NMR, and UV‐vis spectroscopy to be the polyaniline having glucose residues attached to the general polyaniline unit. Participation of the ortho‐position of the aromatic ring in the polymerization was also confirmed by the analyses.

The oxidative polymerization of N‐glucosylaniline.     

1,3‐Dipolar Cycloaddition Reactions Leading to the Synthesis of New 2,3,5‐Triaryl‐4H,2,3,3a,5,6,6a‐hexahydropyrrolo[3,4‐d]isoxazole‐4,6‐diones

Cycloaddition of C,N‐diphenylnitrones 1 to N‐aryl maleimides 2 afforded two diastereomeric isoxazolidines with high selectivity. The structure and steric configuration of the adducts have been assigned on the basis of ¹H NMR, ¹H NMR COSY, ¹³C NMR and IR spectroscopy. The π–π stacking interactions between maleimide's and nitrone's aromatic rings during the 1,3‐dipolar cycloaddition were assumed to control the exo–endo selectivity of the reaction. Thus, the exo–endo ratio depends upon the position of the substituent present on the C‐phenyl ring of the C,N‐diphenylnitrones.     

Heterylation of 3-R1-5-R2-1,2,4-Triazoles with Derivatives of 3,5-Dinitro-1,2,4-Triazole

Heterylation of 3-R¹-5-R²-1'2'4-triazoles (pK _a 3-12) with N-alkyl-, N-alkenyl-, N-alkoxy-carbonyl-, N-oxoalkyl-, N-nitroxyalkyl, N-nitroaminoalkyl-3'5-dinitro-1'2'4-triazoles results insubstitution of a nitro group in 5 position of the dinitro compound yielding 1-R-methyl-3-nitro-5-(3-R¹-5-R²-1,2,4-triazolyl)-1,2,4-triazoles. The side processes: Hydroxide-ion attack on C⁵ and (or) N¹ of the ring both in the substrate and in the target compound afford 1-R-methyl3-nitro-1,2,4-triazol-5-ones, 3,5-dinitro-1,2,4-triazole and NH-acids of N-C-bitriazole series. Optimal reaction media are aprotic dipolar substances, and for compounds prone to heterolysis ethyl acetate-water systems. The azole pK _a is the decisive factor controlling the composition and the ratio of reaction products. The process is promising for azoles with pK _a > 5, and the optimal range of pK _a is 8-10.     

Sels de Pyrylium. XVIII. Etude par RMN du Carbone-13 de Sels d'Aminopyrylium et des Barrières de Rotation dans quelques Cations N,N-Diméthylaminopyrylium

The C-2—N bond of 2-N,N-dimethylaminopyrylium cations has a partial π character due to the conjugation of the nitrogen lone-pair with the ring. The values of ΔG^≠, ΔH^≠, ΔS^≠ parameters related to the corresponding hindered rotation have been determined by ¹³C NMR total bandshape analysis. This conjugation decreases the electrophilic character of carbon C-4 so that the displacement of the alkoxy group is no longer possible. Such a hindered rotation also exists in 4-N,N-dimethylaminopyrylium cations and the corresponding ΔG^≠ parameters have been evaluated. Comparison of these two cationic species shows that hindered rotation around the C—N bond is larger in position 4 than in position 2. Furthermore, the barrier to internal rotation around the C-2? N bond decreases with increasing electron donating power of the substituent at position 4. ΔG^≠ values decreases from 19.1 kcal mol^?1 (79.9 kJ mol^?1) to 12.6 kcal mol^?1 (52.7 kJ mol^?1) according to the following sequence for the R-4 substituents: -C₆H₅, -CH₃, -OCH₃, -N(CH₃)₂.     

Nucleophilic displacements of N-aryl and heteroaryl groups. Part 8 . Intermolecular reactions of N-aryl-pyridinium, -quinolinium,and -acridinium salts with nucleophiles

N-Aryl-mono-, -tri- and -pentacyclic pyridinium cations react with S- and C-nucleophiles to give: (i) simple addition of hydride at the α-ring position, (ii) nucleophilic addition of thiophenoxide at the γ-ring position, (iii) deprotonation at the 6-position of a 5,6-dihydroquinolinium ring followed by prototropic shift to give a 1,2-dihydroquinoline derivative, (iv) ring contraction of a pyridine to a pyrrole ring, and (v) nucleophilic displacement of the N-aryl group.     

Analysis of fine splittings in the fourier transform 1H magnetic resonance spectra of some 15N labeled borazine derivatives

Proton NMR spectra are reported for ¹⁵N enriched borazine and a series of ¹⁵N enriched derivatives: N-methyl-borazine, N,N′-dimethylborazine and a new photochemical product, 1-methyl-2-aminoborazine. Chemical shifts for the ring (¹⁵N? H) protons have been measured. Using a Fourier transform spectrometer, fine structure in the ¹⁵N? H doublet is resolved. Ortho and meta ring proton and three-bond ¹⁵N to H coupling constants have been determined. Substituent effects on chemical shifts and coupling constants for borazine derivatives are compared with those for analogous benzene derivatives.     

Carbon-13?proton coupling constants in N-substituted imidazoles. A 13C NMR study and MO calculations

The ¹³C NMR data of imidazole, and N-methyl-, N-acetyl-, N-trifluoroacetyl-, N-heptafluorobutyryl- and 2-methyl-imidazoles, were obtained from proton-noise decoupled and single frequency NOE ¹³C NMR spectra. The considerable changes in the directly-bonded (C, H) coupling constants upon N-acetylation of the imidazole ring, which are comparable to those noted when going from the neutral to the cationic form of imidazole, are primarily due to the large π-electron transfer ability of the N-acetyl- and N-trifluoroacetyl-substituents. The differences in magnitude of the three-bond (C, H) coupling constants along different paths in the imidazole ring may be attributed to the larger π-contributions across a pyridine-like nitrogen than along a pyrrole-like nitrogen.     

Heteronuclear multiple magnetic resonance studies of quaternary ammonium salts derived from heterocyclic bases

¹⁴N tickling experiments performed with simultaneous decoupling of substituent protons are used to show that ²J(¹⁴N? H_ortho) and ³J(¹⁴N? H_meta) are both positive in the N-methyl pyridinium ion and related species. Long range coupling extending over as many as five bonds is observed between N-methyl protons and ring protons in ¹⁴N-decoupled spectra. Triple resonance decoupling is used to permit an analysis of the AA′MM′ spin system given by the ring proton of N-methyl pyrazinium iodide.     

Amine‐blocked polyisocyanates. I. Synthesis of novel N‐methylaniline‐blocked polyisocyanates and deblocking studies using hot‐stage fourier transform infrared spectroscopy

A series of substituted N‐methylaniline‐blocked polyisocyanates based on 4,4′‐methylenebis(phenyl isocyanate) and poly(tetrahydrofuran) were prepared and characterized thoroughly with FTIR, ¹H NMR, and ¹³C NMR spectroscopy methods. Compared with unsubstituted N‐methylaniline, a blocking agent with an electron‐releasing substituent at the para position took a shorter time, whereas those with an electron‐releasing substituent at the ortho position or an electron‐withdrawing substituent at the ortho and para positions took longer times for the blocking reaction. The thermal dissociation reactions of blocked polyisocyanates were carried out with an FTIR spectrophotometer attached to hot‐stage accessories under dynamic and isothermal conditions. The dynamic method was used to determine the deblocking temperature, and the isothermal method was used to calculate the deblocking kinetics and activation parameters. The cure times of blocked polyisocyanates with hydroxyl‐terminated polybutadiene were also determined. The deblocking temperatures, the results of cure‐time studies, and the kinetic parameters revealed that the thermal dissociation of the N‐methylaniline‐blocked polyisocyanates was retarded by electron‐donating substituents and facilitated by electron‐withdrawing substituents. The action of N‐methylanilines as blocking agents for isocyanate was explained by the formation of a four‐center, intramolecularly hydrogen‐bonded ring structure during the thermal dissociation of the blocked polyisocyanates. The formation of such a hydrogen‐bonded ring structure was confirmed and supported by variable‐temperature ¹H NMR studies and entropy parameters, respectively. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1557–1570, 2007     

Conformational Features of 7,8,13β,14α-Tetrahydro-N7-methylcorysaminium,a biosynthetic intermediate to the protopine-type alkaloid corycavine

The crystal structure of (±)-7,8,13β,14α-tetrahydro-N⁷-(¹³C)methylcorysaminium iodide (¹³C- 3a ·I) was investigated by X-ray analysis and thus the relative configuration (7S*,13S*,14S*) established (Fig. 1). The conformation of 3a was shown to have a cis-junction of the B/C rings and the rings A and D in an antiperiplanar position relative to the C(13)? C(14) bond (‘anti-cis’), a twisted half-chair for ring B, and a half-chair for ring C (Figs. 2 and 3). Conformation analysis by ¹H-NMR data indicated that the crystal conformation of 3a is also the preferred one in MeOH solution.     

Synthesis of Artificial Glycoconjugate Polymers Carrying 6-O-Phosphocholine α-D-Glucopyranoside,Biologically Active Segment of Main Cell Membrane Glycolipids of Mycoplasma Fermentas

ABSTRACT

The conformation of two mannose-based amidines, the N-benzylmannoamidine and a pseudo (1→6) dimannoside, has been evaluated using semi-empirical AMI calculations and ¹H NMR studies. The most stable conformations of the mannoamidine ring correspond to the half-chair forms ³H₄ and ⁴H₃. The conformations (Z) or (E) about the exocyclic C-N bond depend on the substituents and it was shown that, in solution, the N-benzylmannoamidine was (E)-configured whilst the pseudo (1→6) dimannoside was (Z)-configured. Using the grid-search approach, the potential energy maps of both mannoamidines were calculated as a function of the torsion angles which define the orientation of the amidine substituent. Three stable conformers were identified for the N-benzylmannoamidine and seven for the pseudo (1→6) dimannoside. Inter-glycosidic NOE have provided evidence for a preferred conformation of the pseudo (1→6) dimannoside in solution. The transition state structure of the α-phenylmannose hydrolysis was optimized using the AMI method and compared to the N-benzylmannoamidine. The developing oxocarbenium ion is well matched by the mannoamidine ring but the orientation of the phenyl group in the inhibitor differs significantly from the position of the leaving group in the transition state. The use of sugar type amidines as haptens to obtain catalytic antibodies is then discussed.