Effect of molecular motion and solvent interactions on nitrogen-15 relaxation in anilines

Dipolar relaxation of ¹⁵N in anilines and anilinium ions is influenced by overall motion of the molecule, by rotation about the aryl–-nitrogen bond, by inversion of the aniline nitrogen and by interactions of the NH₂ or NH₃⁺ group with the solvent. These factors are assessed by comparison of the ¹³C and ¹⁵N dipolar relaxation times as a function of para-substitution on the aryl ring. In the anilines (solvent CDCl₃), electron withdrawal brings about faster relative motion of the amine side-chain, contrary to expectation from consideration of C? N rotation but in agreement with the effects from nitrogen inversion. The ¹⁵N dipolar relaxation time correlates with the Hammett σ_p. For the anilinium ions (solvent Me₂SO-d₆), there is no correlation with σ_p and no qualitative relationship with either C? N rotation or N inversion. Nitrogen-15 relaxation, corrected for overall motion as judged by ring ¹³C relaxation, correlates with the inductive parameter σ_I. Electron withdrawal through induction reduces hydrogen bonding and increases side-chain mobility. For most of the anilines and for all of the anilinium ions, solvent interactions cause the nitrogen side-chain to be less mobile than the aryl ring. Under these circumstances, the Woessner approach cannot be used to calculate barriers. The hydrogen bond donor properties of the anilines are reduced in the absence of electron-donating substituents, and the first barriers to NH₂ rotation/inversion were calculated by this procedure: aniline in CDCl₃ 3.5 kcal/mol, p-chloroaniline in CDCl₃ 3.4 kcal/mol and p-nitroaniline in acetone 3.8 kcal/mol.     

Crystallographic rationalization of the reactivity and spectroscopic properties of (2R)‐S‐(2,5‐dihydroxyphenyl)cysteine

At 150 K, the title compound, C₉H₁₁NO₄S, crystallizes in the orthorhombic form as a zwitterion and has a low gauche conformation [χ = −46.23 (16)°] for an acyclic cysteine derivative. A difference in bond length is observed for the alkyl C—S bond [1.8299 (15) Å] and the aryl C—S bond [1.7760 (15) Å]. The –NH₃⁺ group is involved in four hydrogen bonds, two of which are intermolecular and two intramolecular. The compound forms an infinite three‐dimensional network constructed from four intermolecular hydrogen bonds. Characterization data (¹³C NMR, IR and optical rotation) are reported to supplement the incomplete data disclosed previously in the literature.     

NMR study of organosilicon compounds. III—Silicon-29, nitrogen-14, carbon-13 and proton NMR spectra of silylakylamines

²⁹Si, ¹⁴N ¹³C and ¹H NMR data are presented for a series of homologous (methylethoxysilyl)alkylamines of the type (CH₃)_3?n(C₂H₅O)_nSi(CH₂)_mNH₂(n=o to 3; m = 1 to 4). The measured ¹³C and ¹H chemical shifts correlate with the total net charges Q_A on the corressponding atoms, estimated by the Del Re method. ¹⁴N and ²⁹Si chemical shifts which do not show simple linear relationships to the charges are found to correlate with the relative basicities of the compounds. The influence of the remote substituent (? NH₂ and others) on the ₂₉Si chemical shifts is shown to depend on the number and nature of substituents directly on the silicon atom. Argyments for d-orbital participation in the Si? O bounds are given. The chemical shifts of ²⁹Si, ¹⁴N and ₁₃C nuclei are not consistent with the fromation of intramolecular ‘long bonds’ between the solicon and nitrogen atoms in aliphatic silymethylamines.     

Symmetrization of Cationic Hydrogen Bridges of Protonated Sponges Induced by Solvent and Counteranion Interactions as Revealed by NMR Spectroscopy

The properties of the intramolecular hydrogen bonds of doubly ¹⁵N‐labeled protonated sponges of the 1,8‐bis(dimethylamino)naphthalene (DMANH⁺) type have been studied as a function of the solvent, counteranion, and temperature using low‐temperature NMR spectroscopy. Information about the hydrogen‐bond symmetries was obtained by the analysis of the chemical shifts δ_H and δ_N and the scalar coupling constants J(N,N), J(N,H), J(H,N) of the ¹⁵NH¹⁵N hydrogen bonds. Whereas the individual couplings J(N,H) and J(H,N) were averaged by a fast intramolecular proton tautomerism between two forms, it is shown that the sum |J(N,H)+J(H,N)| generally represents a measure of the hydrogen‐bond strength in a similar way to δ_H and J(N,N). The NMR spectroscopic parameters of DMANH⁺ and of 4‐nitro‐DMANH⁺ are independent of the anion in the case of CD₃CN, which indicates ion‐pair dissociation in this solvent. By contrast, studies using CD₂Cl₂, [D₈]toluene as well as the freon mixture CDF₃/CDF₂Cl, which is liquid down to 100 K, revealed an influence of temperature and of the counteranions. Whereas a small counteranion such as trifluoroacetate perturbed the hydrogen bond, the large noncoordinating anion tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate B[{C₆H₃(CF₃)₂}₄]^? (BARF^?), which exhibits a delocalized charge, made the hydrogen bond more symmetric. Lowering the temperature led to a similar symmetrization, an effect that is discussed in terms of solvent ordering at low temperature and differential solvent order/disorder at high temperatures. By contrast, toluene molecules that are ordered around the cation led to typical high‐field shifts of the hydrogen‐bonded proton as well as of those bound to carbon, an effect that is absent in the case of neutral NHN chelates.     

A Spectroscopic Overview of Intramolecular Hydrogen Bonds of NH…O,S,N Type

Intramolecular NH…O,S,N interactions in non-tautomeric systems are reviewed in a broad range of compounds covering a variety of NH donors and hydrogen bond acceptors. ¹H chemical shifts of NH donors are good tools to study intramolecular hydrogen bonding. However in some cases they have to be corrected for ring current effects. Deuterium isotope effects on ¹³C and ¹⁵N chemical shifts and primary isotope effects are usually used to judge the strength of hydrogen bonds. Primary isotope effects are investigated in a new range of magnitudes. Isotope ratios of NH stretching frequencies, νNH/ND, are revisited. Hydrogen bond energies are reviewed and two-bond deuterium isotope effects on ¹³C chemical shifts are investigated as a possible means of estimating hydrogen bond energies.     

1H and 13C nmr studies of salicylalanilines

Several substituted salicylanilines (I) are studied by ¹H (chemical shifts) and ¹³C (chemical shifts and T₁ relaxation times) NMR in order to obtain information on molecular geometry changes and the transmission of the electronic effects due to substituents, as well as on the relative rates of the overall molecular tumbling and of the flipping of the phenyl rings. In particular, a good linear correlation of the OH proton shifts (affected by intramolecular hydrogen bonding) with Hammett's σ constants for p-substitution in the aniline moiety is found. Changes in rigidity of the rings expected as a result of the OH...N interaction and of p-substitution are reflected on the phenyl carbon relaxation times.     

Zinc- and Cadmium meso-Aryl-Isoporphyrins: Non-Aromatic NIR Dyes with Distinct Conformational Features

A series of pyrrolyl and dipyrrinyl isoporphyrins carrying different phenyl and thienyl groups is reported. The compounds are obtained by a one-pot approach in the presence of a template reagent. Thienyl derivatives gave better yields, and were the only subclass to form with steric hindrance. The structural analyses carried out on compounds 1 and 14 revealed distinct conformational differences which are likely to result from an intramolecular NH^…Cl hydrogen bridge of the pyrrolyl subclass. In addition, this hydrogen bridge strongly favors one of the two possible atropisomers. Hindered rotation of the meso-aryl groups is observed only in the cases of methylbenzothienyl derivatives 10 and 15 and leads to the observation of several diastereomers. NIR absorptions up to 923 nm are found throughout. Electrochemical investigations into the 1e⁻ and 2e⁻ reduced species unravel axial ligand exchange dynamics for the zinc isoporphyrin radical, and the probable formation of a zinc phlorinate.     

13C NMR spectra of non-labelled and 15N-mono-labelled azo dyes

¹³C NMR spectra of four types of azo coupling products from benzenediazonium chloride have been measured and interpreted, viz. hydrazo compounds with an intramolecular hydrogen bond (3-methyl-1-phenylpyrazole-4,5-dione 4-phenylhydrazone), azo compounds without an intramolecular hydrogen bond (4-hydroxyazobenzene), azo compounds with an intramolecular hydrogen bond (2-hydroxy-5-tert-butylazobenzene) and an equilibrium mixture of both the tautomers of 1-phenylazo-2-naphthol. The absolute values of the J(¹⁵N¹³C) coupling constants have been determined by recording the spectra of the ¹⁵N isotopomers, and have been used, in some cases, for ¹³C signal assignment. A relationship has been found between the chemical shifts of the C-1′ to C-4′ carbons of the phenyl group (from the benzenediazonium ion) or the ¹J(¹⁵N¹³C) coupling constant, and the composition of the tautomeric mixture.     

Synthesis and stereochemistry of 3‐acetyl‐5‐aminospiro[1,3,4‐thiadiazoline‐2,4′‐thioflavans]

Under acetylating conditions racemic thioflavanone thiosemicarbazones cyclize into racemic 3‐acetyl‐spiro[1,3,4‐thiadiazoline‐2,4′‐thioflavans] and a racemic 3‐acetylspiro[1,3,4‐oxadiazoline‐2,4′‐thioflavan] with trans O(1) or S(1) and Ph(2′_eq). Hindered rotation of the endocyclic N(3) acetyl group spirothia‐diazolines caused the formation of isomers separable by HPLC. X‐ray diffraction analyses, ¹H‐, ¹³C‐, and ¹⁵N NMR measurements as well as MOPAC QM calculations were performed to reveal the structures of these isomers.     

A ‘shiftless’ relaxation reagent for metal nuclide and nitrogen-15 magnetic resonance in aqueous solution

Addition of small amounts of [Gd(2 : 2 : 1)]³⁺ cryptate to aqueous solutions containing ¹¹¹Cd²⁺ or formamide decreases metal nuclide or nitrogen-15 spin-lattice (T₁) relaxation times without affecting cadmium or nitrogen chemical shifts. This cryptate is thereby demonstrated to have substantial promise for greatly decreasing the time necessary to obtain natural abundance metal nuclide or ¹⁵N NMR spectra with satisfactory signal-to-noise ratios for many compounds with long metal or ¹⁵N relaxation times.     

Heteronuclear NMR spectroscopic investigations of hydrogen bonding in 2‐(benzo[d]thiazole‐2′‐yl)‐N‐alkylanilines

The 2‐(benzo[d]thiazole‐2′‐yl)‐N‐alkylanilines have previously revealed the presence of a strong intramolecular hydrogen bond. This in turn gives rise to a more complicated multiplet for the protons attached to the carbon adjacent to the amino group. This intramolecular hydrogen bond was investigated by a deuterium exchange experiment using heteronuclear NMR spectroscopy (¹H, ¹³C, ¹⁵ N and ²H). We observed changes in the multiplet structure and chemical shifts providing further evidence that the deuterium replaces the hydrogen in the intramolecular hydrogen bond. A time course study of the D₂O exchange confirmed the presence of a strong hydrogen bond. The comparison of the structures obtained by X‐ray crystallography showed a very small difference in planarity between the two‐substituted and four‐substituted amino compounds. In both the cases, the phenyl ring is not absolutely coplanar with the thiazole unit. The existence of this intramolecular hydrogen bond in 2‐(benzo[d]thiazole‐2′‐yl)‐N‐alkylanilines was further confirmed by single crystal X‐ray crystallography. Copyright © 2015 John Wiley & Sons, Ltd.     

n-π-Interaction in Enamines and Enaminoketones. A 15N-NMR. Study

¹⁵N-Chemical shifts of 32 enamines, 11 enaminoketones and 28 closely related amines have been determined with the isotope in natural abundance. In order to eliminate substituent effects, differential chemical shifts Δδ(N) are defined as δ_N(amine)-δ_N(enamine). This parameter is shown to correlate well with the free enthalpy of activation ΔG# for restricted rotation about the N? C(α) bond in enamines with extended conjugation. Δδ(N) values of substituted anilinostyrenes correlate also with ¹³C-chemical shifts of the β-carbon in the enamine system and with Hammett σ-constants of the aniline substituents. The experimental results suggest that differential ¹⁵N shifts are a useful probe to study n, π-interaction in enamines.     

Stereospecificity of 1H, 13C and 15N shielding constants in the isomers of methylglyoxal bisdimethylhydrazone: problem with configurational assignment based on 1H chemical shifts

In the ¹³C NMR spectra of methylglyoxal bisdimethylhydrazone, the ¹³C‐5 signal is shifted to higher frequencies, while the ¹³C‐6 signal is shifted to lower frequencies on going from the EE to ZE isomer following the trend found previously. Surprisingly, the ¹H‐6 chemical shift and ¹J(C‐6,H‐6) coupling constant are noticeably larger in the ZE isomer than in the EE isomer, although the configuration around the –CH═N– bond does not change. This paradox can be rationalized by the C–H?N intramolecular hydrogen bond in the ZE isomer, which is found from the quantum‐chemical calculations including Bader's quantum theory of atoms in molecules analysis. This hydrogen bond results in the increase of δ(¹H‐6) and ¹J(C‐6,H‐6) parameters. The effect of the C–H?N hydrogen bond on the ¹H shielding and one‐bond ¹³C–¹H coupling complicates the configurational assignment of the considered compound because of these spectral parameters. The ¹H, ¹³C and ¹⁵N chemical shifts of the 2‐ and 8‐(CH₃)₂N groups attached to the –C(CH₃)═N– and –CH═N– moieties, respectively, reveal pronounced difference. The ab initio calculations show that the 8‐(CH₃)₂N group conjugate effectively with the π‐framework, and the 2‐(CH₃)₂N group twisted out from the plane of the backbone and loses conjugation. As a result, the degree of charge transfer from the N‐2– and N‐8– nitrogen lone pairs to the π‐framework varies, which affects the ¹H, ¹³C and ¹⁵N shieldings. Copyright © 2012 John Wiley & Sons, Ltd.     

The distribution of stereochemical configurations in polystyrene as observed with 13C NMR

¹³C NMR configurational assignments are made for an amorphous polystyrene sample examined at 25.2 MHz and 120°C. The assignments are based strictly on a one-parameter Bernoullian fit that was in satisfactory agreement with the nine observed methylene relative intensities. The methylene regions of the ¹³C NMR spectra of a polystyrene were examined before and after hydrogenation of the side-chain phenyl substituents. It was concluded that ring current effects have influenced the ¹³C methylene chemical shifts substantially and are limited largely to contributions from adjacent phenyl substituents. In addition, aromatic substituent parameters are reported that can be used in conjunction with the Grant and Paul parameters for calculating chemical shifts in aromatic hydrocarbons and polymers. Finally, it is concluded that free-radical and n-butyllithium-prepared polystyrenes have essentially atactic structures with meso additions favored over racemic additions by approximately 55/45.     

The conformation of meso and racemic 2,3,4-trichloropentanes—model compounds for polymers derived from 1,2-dichloroethylenes

On the basis of coupling constants and chemical shifts the conformation of meso and racemic 2,3,4-trichloropentanes have been determined. The meso isomer exists as an equilibrium between the expected rotameric forms but the racemic isomer is anomalous and exists almost entirely as a distorted form of a rotamer which has parallel 1:3 interactions. The significance of these conformations is discussed in relation to the likely conformation and stability of the corresponding stereoregular polymers, which may be derived from cis- and trans-1, 2-dichloroethylene.     

Multinuclear two-dimensional NMR: Assignments of natural abundance polypeptide 13C, 1H and 15N chemical shifts and demonstration of isomer interconversion

The polypeptide carbobenzoxy-glycyl-L -prolyl-L -leucyl-L -alanyl-L -proline (0.2 M in DMSO-d₆) was investigated using ¹³C, ¹H and ¹⁵N NMR in natural abundance at 4.7 tesla. The existence of cis–trans-Gly-Pro and -Ala-Pro bonds permits up to four isomers, and all four were observed (in a 60:30:7:3 ratio). ¹³C shifts of the proline β-CH₂ resonances are consistent only with the 60% form being trans–trans. The 30% form is either trans–cis or cis–trans (order as above) and was tentatively assigned as cis-trans on the basis of relaxation behavior. Refocused INEPT studies aided the ¹³C assignments. The ¹⁵N data were obtained using both NOE and INEPT excitation, with signals evident for the three major isomers. The spectra were analysed by starting from the ¹³C data, which were assigned based on known regularities in peptide spectra. A ¹³C? ¹H heteronuclear two-dimensional chemical shift correlation experiment allowed direct assignment of proton shifts for major and minor isomers. The NH proton shifts were assigned by running a homonuclear two-dimensional chemical shift correlation experiment and noting the correlation with the previously assigned α-CH protons. The ¹⁵N resonances were then assigned from a ¹⁵N? ¹H heteronuclear two-dimensional chemical shift correlation experiment, relating the ¹⁵N signals directly to the NH proton resonances. Isomer interconversion between the two major isomers was demonstrated by performing a magnetization transfer homonuclear 2D experiment. Off-diagonal intensity was noted relating the major and minor isomer alanine NH proton, as well as for the major and minor isomer leucine NH protons.     

15N NMR spectral parameters of compounds of the N-methylpyrazole series

The¹⁵N NMR chemical shifts and¹⁵N-¹H SSCCs are presented for substituted N-methylpyrazoles with substituents such as CH₃, NO₂, Br, Cl, NH₂, O=CNH₂, O=CPh, and COOH at the carbon atoms. The¹⁵N chemical shifts of the cyclic atoms of nitrogen and the nitro groups are discussed as well as the geminal and vicinal SSCCs of the ring nitrogen atoms with the hydrogen atoms of the CH and CH₃ fragments.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117334 Moscow. D. I. Mendeleev Chemico-Technological Institute, Moscow, Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 2554–2561, November, 1992.     

Correlation between the reactivity and spectroscopic properties of N‐substituted secondary thioamides. New intramolecular N···H+···N binding approach and proton complexes based on thioamide ligation

On the basis of a comparison of chemical shifts and wavenumbers of several secondary thioamides and amides having monocationic substituents attached to thiocarbamoyl or carbamoyl groups by a polymethylene chain, new intramolecular unconventional N···H⁺···N hydrogen bonding effects were discovered. It is argued that the CH₂—N rotation is hindered and two ⁺H···NHCH₃ non‐equivalent protons occur in a proton spectrum of hydrochloride 1a (at 10.68 and 2.77 ppm, respectively) instead of two ⁺NH₂CH₃ protons. Presumably, the above steric factors inhibit the acidic hydrolysis of 1a (stabilized by strong intramolecular N···H⁺···N hydrogen bonds) to an amide and prevent intramolecular cyclization of 2a (stabilized by strong intramolecular neutral–neutral N···HN hydrogen bonds) to a cyclic amidine. Postulation of additional dihydrogen bond formation is helpful in understanding the spectroscopic differences of 4 and 5 . The above new bonding is also compared with intramolecular N···H—N⁺ hydrogen bonds in primary amine salts 7 and 8 . In contrast to 3 , a cooperative hydrogen bonded system is observed in 9 and 10 . The weak hydrogen bonds in 7 – 10 facilitate the hydrolysis and cyclization reactions of secondary thioamides. The spectroscopic data for secondary (thio)amides are especially useful for characterizing the electronic situation at the (thio)carbamoyl nitrogen atoms and they are perfectly correlated with the reactivity. Examples of chelation of protons by thioamides ( 11 and 12 ), which contain strongly electron‐donating pyrimidine groups, are presented to show the contribution of dihydrogen bonding in the protonation reaction similar to 1 and 4 . Copyright © 2003 John Wiley & Sons, Ltd.     

Conjugation in Phosphabutadienes: Ab initio Investigation and NMR Spectral Manifestation: II. Magnetic Shielding in Iminophosphines and Heterobutadienes Derived from Them

The conjugation effects in iminophosphines H₃C-N = P-R (R = H, Hlg, OH, NH₂, PH₂, SiH₃, SH) and heterobutadienes H₃C-N = P-X = CY₂ (X = N, P; Y = NH₂, H) and their manifestations in NMR spectra are analyzed by RHF and MP2 calculations using the 6-31+G and 6-311+G basis sets with different numbers of polarization functions. The contribution of -mesomeric interactions to the electronic structure of these compounds is estimated from the theoretical and experimental structural parameters, calculated natural atomic charges and bond indices, surfaces of rotational coordinates of the potential energy, and energy balances of isodesmic reactions, and also from the experimental and theoretically calculated (GIAO) ¹⁵N and ³¹P NMR chemical shifts. The configuration of model heterobutadienes relative to the P = N double bond and the trans conformation of the N = P-X = C fragment, suggested by the calculation results, are consistent with the structural data for the compounds Mes*-N = P-X = C(NR₂)₂ (X = N, P; R = Alk). The character of -meso-meric interactions in the examined series of iminophosphines and butadienes derived from them is discussed. The conjugation effects influence the stability of phosphabutadienes insignificantly.     

Fast Proton Exchange in Histidine: Measurement of Rate Constants through Indirect Detection by NMR Spectroscopy

Owing to its imidazole side chain, histidine participates in various processes such as enzyme catalysis, pH regulation, metal binding, and phosphorylation. The determination of exchange rates of labile protons for such a system is important for understanding its functions. However, these rates are too fast to be measured directly in an aqueous solution by using NMR spectroscopy. We have obtained the exchange rates of the NH₃⁺ amino protons and the labile NH^ε2 and NH^δ1 protons of the imidazole ring by indirect detection through nitrogen‐15 as a function of temperature (272 K<T<293 K) and pH (1.3<pH<4.9) of uniformly nitrogen‐15‐ and carbon‐13‐labeled L ‐histidine ? HCl ? H₂O. Exchange rates up to 8.5×10⁴ s^?1 could be determined (i.e., lifetimes as short as 12 μs). The three chemical shifts δ_Hi of the invisible exchanging protons H_i and the three one‐bond scalar coupling constants ¹J(N,H_i) could also be determined accurately.