Assignment Of 13C NMR Spectra Research Articles

Application of Quantum–Chemical Methods in the Forensic Prediction of Psychedelic Drugs’ Spectra (IR, NMR, UV–VIS, and MS): A Case Study of LSD and Its Analogs

Lysergic acid diethylamide (LSD) and its analogs are commonly encountered substances at crime scenes due to their misuse as hallucinogenic compounds. Modern methods have led to synthesizing different LSD analogs with pronounced physiological effects. Theoretical methods can be a valuable tool for predicting the spectra and stability of novel substances, especially when experimental data are partially available. The current work describes the application of theoretical methods in predicting IR, NMR, UV–VIS, and MS spectra of LSD based on the optimized structure at the M05-2X/6-311++G(d,p) level of theory. A suitable functional has been determined by comparison of the theoretically obtained geometrical parameters with the experimental ones based on the crystallographic structure. The MAE values for the structure optimized at M05-2X/6-311++G(d,p) level of theory were 0.0436 Å (bond lengths) and 2.70° (bond angles). The IR spectra of LSD and LSD tartrate have been described in detail, with the prominent bands being well reproduced (the difference between experimental and theoretical C=O stretching vibration wavenumbers was lower than 11 cm−1). Detailed assignment of 13C NMR spectra led to a high correlation factor (0.999) and low mean absolute error (2.0 ppm) between experimental and theoretical chemical shifts. Optimizing the ground and excited states allowed for the calculation of the energy difference of 330 nm, which reproduced the observed band position in the UV–VIS spectrum of LSD. The most abundant fragments in the experimental mass spectrum (at 323, 221, 207, 181, and 72 m/z) have been optimized, and their stability has been discussed from the structural point of view. This methodology has been validated by comparison with the experimental GC-MS spectra of sample seized at the crime screen and by structure optimization and computation of NMR spectra of common LSD analogs. The theoretical methods for the structure determination and prediction of spectra show great potential in the fast-developing world of new psychedelics.

Novel Synthesis of N-(1,3-Dioxoisoindol-2-yl)aminothiocarbohydrazide, and its Arylidenes and Glycosylidines as Precursors for Hybrids with Thiadiazoline Ring. Equilibration of the Glycosylidine Open Chain with the Cyclic Structures and Conformation of the Acyclic Analogues

Aim and Objective: Reaction of phthalic anhydride (1) with thiocarbohydrazide (2) in methanol gave the intermediate (6) whose boiling in water or ethanol gave N-(1,3-dioxoisoindol-2-yl)aminothiocarbohydrazide (5); where its Condensation with aldehydes and aldoses 9a-d afforded the respective thiosemicarbazide derivatives. The manno-derivative 10, the D-galacto derivative 11 and the L-arabino derivative 12 exist in the cyclic pyranosyl structures undergo equilibration, in solution of DMSO, with their acyclic structures. Dehydrative cyclization to the thiadiazoline derivatives and the acyclo C-nucleoside was done by refluxing in acetic anhydride. Materials and Methods: Commercially available solvents and reagents were purified according to the standard procedures. Thin layer chromatography (TLC) was performed on plastic plates Silica Gel 60 F254 (E-Merk, layer thickness 0.2 mm) with detection by UV light absorption. IR spectra were recorded for the compounds in a KBr matrix with a Unicam SP 1025 spectrophotometer. NMR spectra were measured with Jeol spectrometer (500 MHz). Chemical shifts (δ) are given in ppm relative to the signal for TMS as internal standard, and coupling constants in Hz. The 13C NMR spectra were recorded with JEOL spectrometer at 125.7 MHz. The assignments of 1H NMR spectra were based on chemical-shift correlation DQFCOSY spectra, while the assignment of 13C NMR spectra were based on heteronuclear multiple quantum coherence, HMQC experiments. Results: The N-(1,3-dioxoisoindol-2-yl)aminothiocarbohydrazide (5) was prepared, which incorborated the 1,3-dioxoisoindole ring that linked to thiosemicarbazide moiety. Such feature found to be excellent precursor for the synthesis of hybrid of bi-heterocycles, the dioxoisoindolyl and thiadiazoline rings which could of potential biological activity. The reaction of thiocarbohydrazide with phthalic anhydride in a detailed manner and investigate its further reaction with aromatic aldehydes and sugars, then converting them to the target biheterocycles and nucleosides was studied. The conformations of the acyclic alditolyl residues or the acyclic Cnucleosides have been explained. Conclusion: The new functionalized isoindolyl ring with thiosemicarbazide as in N-(1,3-dioxoisoindol-2- yl)aminothiocarbohydrazide (5) resulted from the reaction of phthalic anhydride with thiocarbohydrazide via the intermediate open chain derivative 6. It is a valuable precursor for the synthesis of thiosemicarbazones containing sugar moieties 10-13. Their solutions in DMSO-d6 showed that the products exist in one form after immediate dissolution that equilibrated with time to show a mixture of acyclic and cyclic forms. They have been exploited as scaffolds for generation of potential hybrids of thiadiazoline derivatives containing isoindolyl rings as well as their acyclo C-nucleosides 10a-13a and 14-15. The conformations of the acyclic alditolyl residues or the acyclic C-nucleosides have been deduced from their spectral analysis.

Density Functional Theory Study of the Effects of Substituents on the Carbon-13 Nuclear Magnetic Resonance Chemical Shifts of Asphaltene Model Compounds

Petroleum asphaltenes are a complex mixture of organic molecules containing mainly fused polyaromatic and naphthenic systems and pendant chains, polar moieties with heteroatoms (S, N, and O), and transition metals. A variety of spectroscopic techniques has been employed to characterize asphaltenes, but their structures remain largely elusive because of the complexity, variety of samples, and assignment limitations. Carbon-13 nuclear magnetic resonance (13C NMR) spectroscopy has contributed extensively to asphaltene characterization. However, proper assignment of 13C NMR spectra is very challenging because spectra of natural asphaltenes feature a large number of peaks in unusual environments, which may be hard to assign and interpret. We employ the dispersion-corrected ωB97X-D density functional with 6-31G(d,p) basis set to rationalize common trends in the 13C NMR chemical shifts of asphaltene model compounds. The calculated 13C NMR chemical shifts for a calibration series of 14 aromatic and heterocyclic reference compounds containing C atoms of types similar to those in the asphaltene model compounds are found to correlate linearly with the respective experimental values. The linear fitting yields a correlation coefficient of R2 = 0.99 and absolute errors of less than 10 ppm. Moreover, we calculate and calibrate the 13C chemical shifts of asphaltenes extracted from Brazilian vacuum residues to analyze and correlate the C atom types with those of the reference compounds. It is found that the presence of heteroatoms as well as environments with a high aromatic condensation index can significantly affect the chemical shifts. The effect of heteroatoms on the chemical shift, a situation that has scarcely been addressed in the literature, is evaluated here in detail. The results are intended to help interpret 13C NMR spectra and allow for a more complete characterization of asphaltene molecules.

INFERCNMR: A 13C NMR Interpretive Library Search System

INFERCNMR is an automated (13)C NMR spectrum interpretation aid for use either as a stand-alone program or as a component of a comprehensive, computer-based system for the characterization of chemical structure. The program is an interpretive library search which requires a database of assigned (13)C NMR spectra. An interpretive library search does not require overall structural similarity between an unknown and a library entry in order to retrieve a substructure common to both. Input consists of the chemical shift and one-bond proton-carbon multiplicity of each signal in the spectrum, and the molecular formula of the unknown. Program output is one or more substructures predicted to be present in the unknown, each of which is assigned an estimated prediction accuracy.

ChemInform Abstract: A Novel One-Step Synthesis of 4H-Furo(3,4-b)pyrans and a Transformation into a Difuro(3,4-b:3′,4′-e)pyridine.

A simple one-step synthesis of 2-amino-4-aryl-5-oxo-4H-furo[3,4-b]pyran-3-carbonitriles 7 is described. It involves reaction of 2,4(3H,5H)-furandione (β-tetronic acid) (5) with arylmethylenemalononitriles 4 in basic medium. Some substituent effects are noted and the assignments of 13C-NMR spectra are discussed. Ring transformation of the furo[3,4-b]pyran 7a leads to the difuro[3,4-b:3′,4′-e]pyridine 9.

UV–visible, 1H and 13C NMR spectroscopic studies on the interaction between protons or alkaline earth metal ions and the benzoate ion in acetonitrile

The interaction between protons (H +) or alkaline earth metal ions (Mg 2+, Ba 2+) and the benzoate ion has been examined in acetonitrile by means of UV–visible, 1H and 13C NMR spectroscopy. The assignments of 13C NMR spectra for the benzoate ion (L −), benzoic acid (HL), and the protonated benzoic acid (H 2L +) in acetonitrile were properly performed by means of theoretical calculations, including the influence of the acetonitrile solvent by using the self-consistent isodensity polarized continuum model and the polarized continuum model. It is demonstrated that “strong” interactions of alkaline earth metal ions (M 2+ = Mg 2+, Ba 2+) with the benzoate ion (L −) lead to the formation of mono-charged species, ML +, as well as non-charged species, ML 2, in acetonitrile solution: the strong ability in coordination for alkaline earth metal ions is verified.

Assignment of 13C NMR spectrum for blepharismin C based on biosynthetic studies

Blepharismins, toxic pigments of the ciliate Blepharisma japonicum, are polycyclic ring-condensed compounds. Assignment of 13C NMR signals for blepharismin C, a major constituent of blepharismins, was achieved by analyses of the HMQC, HMBC, and INADEQUATE spectra of 13C-enriched samples obtained by feeding experiments using sodium [1- 13C], [2- 13C], and [1,2- 13C 2]acetates.

Flash vacuum pyrolysis of stabilised phosphorus ylides. Part 17.1 Preparation of aliphatic amino acid derived γ-alkoxycarbonylamino-β-oxo ylides and pyrolysis to give α,β-acetylenic γ-amino acid and GABA analogues

A series of eleven α-aminoacyl stabilised phosphorus ylides 9–19 have been prepared by condensation of N-alkoxycarbonyl protected amino acids with Ph3PCHCO2Et using a carbodiimide peptide coupling reagent. Upon flash vacuum pyrolysis at 600 °C, these undergo extrusion of Ph3PO to give the corresponding α,β-acetylenic γ-amino esters 21–29, 33 and 34 in moderate yield. In two cases the terminal alkynes 30 and 31 are also formed. The β-aminoacyl ylide 20 from β-alanine similarly gives the α,β-acetylenic δ-amino ester 35 upon pyrolysis. Regioselective addition of HBr to the triple bond of one acetylenic ester 25 was observed giving a mixture of E and Z α-bromoacrylates 36. Hydrogenation of the N-Cbz acetylenic esters 21–23 and 33 results in N-deprotection and hydrogenation of the triple bond to afford the chiral GABA analogues 37–40 in 70 –>95% ee as determined by 19F NMR of their Mosher amides. Fully assigned 13C NMR spectra of all the ylides and acetylenic ester derivatives are presented.

High field NMR analysis of the degree of substitution in carboxymethyl cellulose sodium salt

An accurate high field ( 1H at 600.13 MHz) 1D and 2D study was performed on an aqueous solution of carboxymethyl cellulose (CMC) sodium salt at 90°C. A combination of 2D experiments was used, 1H– 1H totally correlated spectroscopy TOCSY, and reverse detected 1H– 13C hetero-correlated spectroscopy HMQC with gradient selection. This combination allows a full assignment of 13C NMR spectra. From the gated decoupled 13C spectrum it is then possible to obtain not only the degree of substitution but also a good measure of the amount of esterification in each chemical position. Conductimetric titration supports the obtained results.

GIAO NMR calculations for carbazole and its N‐methyl and N‐ethyl derivatives. Comparison of theoretical and experimental 13C chemical shifts

High-level ab initio calculations were performed at the restricted Hartree–Fock (RHF) level of theory on carbazole and its N-methyl and N-ethyl derivatives. Single-point gauge-invariant atomic orbitals (SP GIAO) RHF NMR calculations on ab initio RHF optimized geometries were performed. The 6–31G* and 6–311++G** basis sets were used and some calculations were performed within a density functional theory using a recent B3PW91 hybrid functional. The theoretically predicted multinuclear magnetic resonance chemical shifts of carbazole and its N-methyl and N-ethyl derivatives in the gas phase are compared with experimental NMR data in CDCl3 solutions. A revised assignment of 13C NMR spectra of simple carbazoles is proposed. Copyright © 2000 John Wiley & Sons, Ltd.

GIAO NMR calculations for carbazole and itsN-methyl andN-ethyl derivatives. Comparison of theoretical and experimental13C chemical shifts

High-level ab initio calculations were performed at the restricted Hartree–Fock (RHF) level of theory on carbazole and its N-methyl and N-ethyl derivatives. Single-point gauge-invariant atomic orbitals (SP GIAO) RHF NMR calculations on ab initio RHF optimized geometries were performed. The 6–31G* and 6–311++G** basis sets were used and some calculations were performed within a density functional theory using a recent B3PW91 hybrid functional. The theoretically predicted multinuclear magnetic resonance chemical shifts of carbazole and its N-methyl and N-ethyl derivatives in the gas phase are compared with experimental NMR data in CDCl3 solutions. A revised assignment of 13C NMR spectra of simple carbazoles is proposed. Copyright © 2000 John Wiley & Sons, Ltd.

Flash vacuum pyrolysis of stabilised phosphorus ylides. Part 16. Model studies for the construction of conjugated polymers

Reaction of a range of bis(ylides) with acid chlorides has been used to prepare the bis(oxoylides) 11–15. Similarly a range of simple ylides react with bis(acid chlorides) to give bis(oxoylides) 19–27 with the isomeric structure. Flash vacuum pyrolysis (FVP) of one example of the first type results in extrusion of Ph 3P rather than the expected Ph 3PO while six examples of the second type do extrude Ph 3PO upon FVP at 500 °C to afford the bis(alkynes) 28. Examples of the corresponding bis(tributylphosphonium ylides) have also been prepared but attempts to construct a tetrakis(oxoylide) 31 using a stepwise approach were unsuccessful. Fully assigned 13C NMR spectra are presented for six of the bis(oxoylides).

Multivariate Regression with Substituent Shift Increments. III. 2,5-Disubstituted Furans

Six series of 2-X-5-Y-substituted furans were used for multivariate regression of 13C NMR chemical shifts with four substituent shift increments (SSI). Some of these series were measured in CDCl3 and DMSO-d6 on different spectrometers to exclude possible sources of deviation from the general trends. Program ASSIGN was written for visual and numerical estimation of correct assignment of 13C NMR spectra in the series of derivatives. Multivariate regression proved that the corresponding position in benzenes and furans are not affected by the substituents in the same way: in 2-X-5-Y-substituted furans, the "ortho" position requires correction for the different bond order, the "meta" 13C chemical shift is probably affected by change in diamagnetic contribution of the Y group, and "para" position behaves like another "ortho" position in the molecule.

Stereochemical Assignment of 13C NMR Spectra of Predominantly Syndiotactic Polystyrene

In the present work, predominantly syndiotactic polystyrene samples were prepared with different catalysts and polymerization conditions and the obtained polymers were used for assignments of stereochemical structures of polystyrene. Assignment was carried out by comparison of 13C NMR spectra of polystyrenes with different syndiotacticity and based on polymerization mechanism. Assignments were also compared with results in the previous work.

The solution structure of β,γ-dioxoalkyl(triphenyl)phosphonium salts

The simple phosphonium salts 4 and 5 have been fully characterised for the first time and are found by NMR spectroscopy to exist in CDCl 3 solution mainly as the E and Z enol structures b and c. The salt 6 exists as a mixture of the keto form a and one enol form assumed to be b. Similarly the bis(phosphonium salt) 16 exists entirely with one end in the keto form and the other in the enol form. The ylide/phosphonium salt 17 obtained from 16 by treatment with base also exists as an enol which is resistant to further deprotonation. Fully assigned 13C NMR spectra are presented for all the structures involved.

Solution and Solid State Structure of Highly Delocalised 5- Triphenylphosphoranylidenecyclopen Tene-3,4-Diones

The fully assigned 13C NMR spectra of the cyclic ylides 4 and 5 show that the C-1-C-2 bond is very strongly polarised consistent with substantial delocalisation of the ylide negative charge on to C-2. The X-ray structure of 5 confirms the occurrence of extensive delocalisation involving a significant contribution from up to six separate resonance forms.

A Simple Aid to the Assignment of 13C NMR Spectra, based on the Visual Differences caused by Deuteriation

Selective deuteriation of complex polyheterocyclic compounds effects changes in the intensities of the 13C NMR signals which can be used to solve assignment problems.

Flash vacuum pyrolysis of stabilised phosphorus ylides. Part 14.1 Tandem cyclisation of intermediate aryloxy and arylthio radicals leading to tri- and tetra-cyclic aromatic heterocycles

Seven new stabilised phosphorus ylides 8–14 designed to undergo thermal tandem cyclisation have been prepared. Upon flash vacuum pyrolysis at 850 °C, loss of Ph3PO and Me˙ results in tandem cyclisation to give benzothieno[3,2-b]benzothiophene 16 in the case of 11 while for 8 an abstraction–rearrangement–extrusion sequence leads to 2-phenylbenzofuran 18. For 9 and 10 both types of process occur to give respectively benzothieno[3,2-b]benzofuran 27, prepared here for the first time, and 2-phenylbenzothiophene 29. For 12 and 13, initial cyclisation is followed by intramolecular addition and aromatisation to give the tricyclic products 31 and 32, while for 14 intramolecular homolytic substitution leads to the tetracyclic benzonaphthofuran 34 and, by rearrangement, to the isomer 37. Fully assigned 13C NMR spectra are presented for all seven ylides.

Automated Spectrum Simulation Methods for Carbon-13 Nuclear Magnetic Resonance Spectroscopy Based on Database Retrieval and Model-Building Strategies

An automated method for the prediction of carbon-13 nuclear magnetic resonance (13C NMR) chemical shifts which involves the combined use of database retrieval and multivariate calibration methods is described. A commercial database of chemical structures and experimentally measured and assigned 13C NMR spectra is used to implement this methodology. The chemical environment of each of the carbons in the database is encoded as a vector, and Euclidean distance comparisons are made between these vectors and the similarly encoded environment of a target carbon whose chemical shift is to be predicted. This procedure yields a calibration set of carbon atoms with chemical environments similar to that of the target carbon. If the environment of the closest match is very similar to that of the target carbon, the predicted chemical shift is assigned as the chemical shift of that closest match (i.e., a direct chemical shift retrieval is performed). Otherwise, a chemical shift model based on spectra−structure relation...

Synthesis and pyrolytic behaviour of thiazolidin-2-one 1,1-dioxides

R. Alan Aitken, D. P. Armstrong, R. H. B. Galt and S. T. E. Mesher, J. Chem. Soc., Perkin Trans. 1, 1997, 2139 DOI: 10.1039/A700521K