Phosphorus Derivatives of Natural Lactones. Synthesis of New Grosshemin Dialkylphosphonates

New phosphorus-containing derivatives of grosshemin were synthesized in 68-70% yield by reacting this guaianolide with dialkylphosphites. Their structures were established by IR, PMR, ¹³C NMR, and ³¹P NMR spectroscopies and two-dimensional ¹H-¹H NMR spectroscopy (COSY). The reaction of grosshemin with dialkylphosphites was found to be highly stereoselective.     

Phosphate Derivatives of Natural Lactones. II. Synthesis of Novel Dialkylphosphonates of Arteannuin B

Novel dialkylphosphonates of arteannuin B were synthesized in 45-47% yields by reaction of this cadinanolide with dialkylphosphites. Their structures were established using IR, PMR, ¹³C and ³¹P NMR spectroscopy, and two-dimensional ¹H-¹H NMR (COSY) spectroscopy. The reaction of arteannuin B and dialkylphosphites is highly stereoselective.     

The stereochemistry of a nine-membered ring analogue of nefopam,a nonnarcotic analgesic drug

The solid-state structure of a (±)-homonefopam hydrogenfumarate salt having an-O(CH₂)₃N-fragment was determined by single-crystal X-ray diffraction analysis. Homonefopam hydrogenfumarate gave crystals belonging to the monoclinicP2₁/c space group, and at ambient temperaturea=10.220(1),b=18.187(2),c=10.687(2)A,=94.43(1),V=1980.5(5)å³ Z=4,R(F)=0.039,R _w =0.039,R _W (F)=0.025. The¹H NMR spectrum of homonefopam hydrochloride in CD₂Cl₂ solution showed two species (7:1 ratio) at the prototropic shift-nitrogen inversion slow exchange limit. The solution-state major species has the same conformation andtrans-to-phenyl axial N-methyl disposition found in the crystal as evidenced by three antiperiplanar vicinal³ J (HH) coupling constants in the oxytrimethyleneamino fragment and vicinal coupling constants involving theN-H proton. TheR-ratio method was used to estimate 64(2) O-C(3)-C(4)-C(5) and 75(3) C(3)-C(4)-C(5)-N(6) dihedral angles for the major species in CD₂Cl₂ solution in accord with its proposed structure. The finding of C(3)-C(4) bond time-averaged magnitude³ J (HH) values and severe broadening of signals from other minor species protons suggests conformational heterogeneity for the solution-state minor species.     

~1H–~(15)N HMBC spectra of C_(18)-diterpenoid alkaloids

The normally underused 1H–15N HMBC spectra of thirteen C18-diterpenoid alkaloids have been determined for the first time. As a result, the significant effects of the substituents of nitrogen atoms, the conformations of A ring, and protonation, on the nitrogen-15 chemical shifts are demonstrated.     

1H, 13C,and 14N NMR study of 3-methylfurazans with nitrogen-containing substituents at position 4

3-Methylfurazans with nitrogen-containing substituents at position 4 were studied by ¹H, ¹³C, and ¹⁴N NMR spectroscopy. A correlation between the chemical shifts in ¹³C NMR spectra of these furazans and monosubstituted benzenes with the same substituents was found. The increments for a number of furazan-containing substituents were determined for the first time.     

A multinuclear NMR study in the solid state and in solution of thallium(I) tris-(pyrazol-1-yl)borates (thallium scorpionates)

The ¹H, ¹³C and ¹⁵N NMR spectroscopic properties of six thallium tris-(pyrazol-1-yl)borates, including a tetrakis derivative, were determined. The results in solution were necessary to understand those, more complicated, in the solid state. A collection of ²⁰⁵Tl-¹⁵N and ²⁰⁵Tl-¹³C couplings was measured in the latter state. Among those, a very large coupling constant (between 194 and 282 Hz) has been measured on the carbon at the position 4 of the pyrazole ring in several compounds and particularly for the cyclobutyl derivative [Tl(Tp^Cbu)]. It has been assigned to a direct interaction of the 4-C-H ? Tl type and related to the X-ray structures, when available.     

Nitropyrazoles

The structures of substitutedN-aminonitropyrazoles and 1- and 2-amino-4-nitro-1,2,3-triazoles as well as the site of protonation of 1-aminopyrazole were determined based on the¹H,¹³C, and¹⁵N (¹⁴N) NMR spectra. The¹³C NMR spectra were recorded under conditions of¹³C-{¹H,¹⁴N} triple resonance. Effects of substituents in the pyrazole ring on the¹³C and¹⁴N chemical shifts were studied. The¹³C,¹H and¹⁵N,¹H spin-spin coupling constants, obtained using techniques of [¹H]¹³C and [¹H]¹⁵N polarization transfer (SPT, INEPT), were measured, fully assigned, and discussed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2181–2186, November, 1995.For Part 8, see Ref. 1.     

Phosphate Derivatives of Natural Lactones. I. Synthesis of Novel Isoalantolactone Dialkylphosphonates

Novel isoalantolactone dialkylphosphonates were synthesized in 70-87% yields by reacting this eudesmanolide with dialkylphosphites. Their structures were proved by spectral analysis using IR, PMR, ¹³C and ³¹P NMR, and two-dimensional ¹H-¹H (COSY) spectroscopy. The reaction of isoalantolactone with dialkylphosphites is highly stereoselective.     

Stereochemicai study of 7-aryl-1,7,8,8a-tetrahydro-3(2H)indolizinones by1H and13C NMR

Stereochemistry of 7-aryl-1,7,8,8a-tetrahydro-3(2H)-indolizinones was studied by¹H and¹³C NMR. Complete assignment of¹H NMR signals and analysis of¹H-¹H coupling constants were performed using the iterative PANIC program. Values of³ J _6,7,³ J _7,8endo, and⁴ J _5,7 allow one to unambiguously identify the correspondingexo- andendo-stereoisomers. For stereoisomers with exo-orientation of H(7), complete assignment of¹³C NMR signals was performed on the basis of analysis of the¹³C-¹H coupling constants using two dimensional heteronuclear shift-correlating spectroscopy.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 591–593, March, 1996.     

Ambidentate Properties of Asymmetric Substituted Imidazoles. Direction of Benzylation of 2-[N-(4-Chlorophenyl)carbamoyl]methylthio-4-phenyl-1H-imidazole

On the basis of ¹H-¹H two dimensional NMR spectroscopy (NOESY) it has been unambiguously shown that the benzylation of 2-[N-(4-chlorophenyl)carbamoyl]methylthio-4-phenyl-1H-imidazole occurs at the N₍₁₎ atom. This data was confirmed by comparison of the properties of the alkylation product obtained with the corresponding N₍₃₎-benzylimidazole isomer synthesized independently. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 882–886, June, 2005.     

The crystal structure of a valinomycin•2Ca2+ complex and the multi-step solution equilibria in acetonitrile characterised by 1H NMR,UV–Vis,and mass spectrometry

Valinomycin is a well-known potassium-selective ion carrier, but the nature of its direct interaction with calcium ion, another biologically important cation, is also of considerable interest. We have determined the first crystal structure of a valinomycin–calcium complex, which crystallises exclusively as a 1:2 valinomycin:Ca²⁺ complex, [VCa₂(OTf)₂(H₂O)₂]²⁺ in the solid state (V = valinomycin, OTf = triflate). Along with the 1:2 complex, the solution phase 1:1 and 2:1 complexes have been characterised in acetonitrile by ¹H NMR and UV–Vis titration experiments. The molar absorptivity curves and binding equilibrium constants for these complexes have been determined by the global analysis of the UV–Vis titration data using the program SIVVU?.     

Supramolecular amide and thioamide synthons in hydrogen bonding patterns of N-aryl-furamides and N-aryl-thiofuramides

The supramolecular synthon of amide group in the primary and secondary amides is well recognized to be infinite chains of the C(4) type formed by the intermolecular hydrogen bond of the type N–HO=C. On the other hand, there is a lack of structural data for the thioamides. Three compounds belonging to the class of N-aryl-fura-mides (N-(4-bromophenyl)-5-bromo-2-furancarboxamide, N-(4-chlorophenyl)-5-bromo-2-furancarboxamide) and to the class of N-aryl-thiofuramide (N-(4-methoxyphenyl)-2-furanthiocarboxamide) are prepared and characterized by the NMR spectroscopy in solution; molecular and crystal structures in the solid state have been determined by X-ray single crystal diffractometry and the structures in the gas phase by DFT and AM1 calculations. The investigation is carried out in order to establish supramolecular amide and thioamide synthons of hydrogen bonding patterns in these crystal structures. The geometry of the N–HO=C and the N–HS=C type of hydrogen bonds are compared due to the possibility of the N–H amide group to form intramolecular hydrogen bond with the furan oxygen atom, thus, commonly, leading to the three-center hydrogen bond pattern. The competition between the S=C proton acceptor of thioamides and the other proton acceptors (such as methoxy group) for the amide N–H proton donor group has been investigated. In that context, the above-mentioned compounds are correlated with the others of this class, structurally determined, so far.     

Halide ion effect on the 1H NMR chemical shifts of the residual protons in commonly employed deuterated solvents with tetra-n-butylammonium chloride – Part 2

Many ¹H NMR spectroscopic studies involving supramolecular binding of tetra-n-butylammonium halides (TBAX) with a variety of molecular receptors have been reported to date. Previously we demonstrated that the reference residual proton signal of the deuterochloroform solvent itself in TBAX solutions shifted downfield in a linear TBAX concentration-dependent relationship. We now report that a similar downfield chemical shift behaviour of the residual protons of other commonly employed deuterated solvents with TBACl can be seen for dichloromethane-d₂ and acetonitrile-d₃, but in acetone-d₆, methanol-d₄ and DMSO-d₆, upfield shifts are observed. A hypothesis based on Density Functional Theory (DFT) modelling is presented to account for this behaviour.     

Nuclear magnetic resonance of donor atoms as a tool for determination of the structure of platinum metal complexes in solutions

Data on the NMR spectroscopy of C, N, O, Si, P, and Sn donor atoms of platinum metal complexes in solutions are surveyed. The chemical shift of a donor atom mainly depends on the ligand in the trans-position (due to the trans-effect). The chemical shift of a donor atom on a particular coordinate of the complex (coordinate shift, CSh) is an attribute of this coordinate and can be used to identify such a coordinate in platinum metal complexes and to determine the structures of complexes. Based on the known data, CSh diagrams were composed for ¹H, ¹³C, ¹⁴N, ¹⁷O, ¹⁹F, ³¹P, and ¹¹⁹Sn. Examples of using the CShs for determining the structures of platinum metal complexes in solutions are presented.     

Invertomers at nitrogen in aziridine carboxylates by mltltinuclear (1H,13C,17O,and15N) NMR study

A confrgurational and conformational study of NH, N-acetyl- and N-sulfonylaziridine carboxylates is performed by¹H ,¹³C,¹⁷O, and¹⁵N NMR spectroscopy. The presence of acetyl and su fonyl groups on the ring nitrogen atom seems to reduce greatly the configurational stability at nitrogen.Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1226–1234, September, 1995.     

Rapid and novel discrimination and quantification of oleanolic and ursolic acids in complex plant extracts using two-dimensional nuclear magnetic resonance spectroscopy—Comparison with HPLC methods

A novel strategy for NMR analysis of mixtures of oleanolic and ursolic acids that occur in natural products is described. These important phytochemicals have similar structure and their discrimination and quantification is rather difficult. We report herein the combined use of proton-carbon heteronuclear single-quantum coherence (¹H-¹³C HSQC) and proton-carbon heteronuclear multiple-bond correlation (¹H-¹³C HMBC) NMR spectroscopy, in the identification and quantitation of oleanolic acid (OA) and ursolic acid (UA)in plant extracts of the Lamiaceae and Oleaceae family. The combination of ¹H-¹³C HSQC and ¹H-¹³C HMBC techniques allows the connection of the proton and carbon-13 spins across the molecular backbone resulting in the identification and, thus, discrimination of oleanolic and ursolic acid without resorting to physicochemical separation of the components. The quantitative results provided by 2D ¹H-¹³C HSQC NMR data were obtained within a short period of time (∼14 min) and are in excellent agreement with those obtained by HPLC, which support the efficiency of the suggested methodology.     

Structure Elucidation and NMR Characterization of Two New Cyclophane Derivatives

In the course of our on-going investigation to develop synthetic methods for helical cyclophanes using Diels–Alder methodology, a great variety of polycyclic aromatic compounds have been formed. In some cases, the cycloaddition reactions, in addition to the target compounds, gave rise to unexpected products, which were identified by spectroscopic methods. The structure determination based on NMR measurements and semiempirical calculations of two such new compounds are presented in this paper.