A suggested revised conformation of methylthionitrite as seen by its spectra and preliminary ab initio calculations

A proof has recently been given that gaseous methylthionitrite, CH₃SNO, occurs exclusively (or mainly) in its anti conformation [1]. The present paper claims that existing spectral evidence and ab initio calculations now performed suggest that gaseous methylthionitrite is mainly the syn conformer, the extra stability being of the order 1–2 kcal mol^?1. Methyl group rotation in the syn conformer is hindered by a three-fold barrier of height 689 cm^?1 while the methyl group rotation in the anti conformer is hardly hindered. The syn/anti energy difference and the barriers hindering methyl group rotation closely parallel the corresponding measured quantities in methylnitrite, CH₃ONO.     

2‐Propynyl 2,3,4,6‐tetra‐O‐acetyl‐α‐d‐mannopyranoside

The 2‐propynyl group in the title compound, C₁₇H₂₂O₁₀, adopts an exoanomeric conformation, with the acetylenic group gauche with respect to position C1. Comparison of ¹³C NMR chemical shifts from solution and the solid state suggest that the acetylenic group also adopts a conformation anti to C1 in solution. The pyranose ring adopts a ⁴C₁ conformation. Of the three secondary O‐acetyl groups, that on position O4, flanked by two equatorial groups, adopts a syn conformation, in agreement with recent generalizations [González‐Outeiriño, Nasser & Anderson (2005). J. Org. Chem. 70 , 2486–2493]. The acetyl group on position O3 adopts a gauche conformation, also in agreement with the recent generalizations, but that on position O2 adopts a syn conformation, not in agreement with the recent generalizations.     

A microwave and quantum chemical study of allyltrifluorosilane

The structural and conformational properties of allytrifluorsilane, H₂CCH-CH₂-SiF₃, have been explored by microwave (MW) spectroscopy and high-level ab initio and density functional theory quantum chemical calculations. The microwave spectrum was investigated in the 18-62 GHz spectral regions. The a-type R-branch transitions of one conformer were assigned for the ground as well as for 10 vibrationally excited states. The CC-C-Si chain of atoms in this rotamer takes an anti-clinal (‘skew’) conformation, with a dihedral angle calculated to be 111.6° from the syn-periplanar (0°) conformation. The question whether a CC-C-Si syn-periplanar conformer exists as a high-energy form in the gas phase remains open. In most of the quantum chemical calculations this conformation is predicted to be a transition state. However, in the most advanced calculations (B3LYP/aug-cc-pVTZ level of theory) the syn-periplanar conformer is predicted to be a stable rotamer that is calculated to be 6.5 kJ/mol higher in energy than the anti-clinal form. Since there is no indication in the MW spectrum for the presence of high-energy form(s), it is concluded that the anti-clinal conformer is at least 4 kJ/mol more stable than any other hypothetical rotamer.     

Stereoelectronic Aspects of the Anomeric Effect in Fluoromethylamine

High-level ab initio calculations have been made for fluoromethylamine to study structural and energetic effects of the relative orientation of the N lone pair to the C? F bond. The anti-conformer (N lone pair anti-planar to the C? F bond) corresponds to the global energy minimum. It has the longest C? F distance, the shortest C? N distance, and is 7.5 kcal·mol^?1 more stable than the related perpendicular conformation (lone pair perpendicular to the C? F bond). The syn-conformation also shows hallmarks of the anomeric effect: long C? F bond, short C? N bond, and energetic stability when allowance is made for the two pairs of eclipsed hydrogens. The transition state for N inversion is close to the syn-structure; rotation about the C? N bond is strongly coupled with this inversion process. Small bond distance changes of ca. 0.02 Å between parallel and perpendicular conformations are associated with dissociation energy differences of ca. 30 kcal·mol^?1. Various criteria for assessing the strength of the anomeric effect are discussed.     

Exploring structural and conformational behaviour of cyclophanes incorporating imidazole-2-thiones

New cyclophanes containing two imidazole-2-thione moieties linked by two xylylene groups have been synthesized by the reaction of imidazolium-linked cyclophanes with sulfur in the presence of K₂CO₃. The conformational behaviour of the new cyclophanes was explored by NMR spectroscopy and X-ray diffraction studies. In cyclophanes containing o-xylylene or 2,4,6-trimethyl-m-xylylene linking groups, the imidazole-2-thione groups were mutually syn in both the solid state and in solution, the cyclophanes adopting a conformation reminiscent of the cone conformation of calix[4]arenes. Cyclophanes containing p-xylylene or m-xylylene linking groups exhibited two conformations in solution, one in which the imidazole-2-thione groups are mutually syn, the other in which they are mutually anti, and these conformations did not interconvert on the NMR timescale. Both conformations co-crystallised in the m-xylylene linked cyclophane, while for the p-xylylene-linked cyclophane the anti conformation crystallised separately.     

The Conformational Landscape of Nicotinoids: Solving the Conformational Disparity of Anabasine

The conformational landscape of the alkaloid anabasine (neonicotine) has been investigated by using rotational spectroscopy and ab initio calculations. The results allow a detailed comparison of the structural properties of the prototype piperidinic and pyrrolidinic nicotinoids (anabasine vs. nicotine). Anabasine adopts two most stable conformations in isolation conditions, for which we determined accurate rotational and nuclear quadrupole coupling parameters. The preferred conformations are characterized by an equatorial pyridine moiety and additional N–H equatorial stereochemistry at the piperidine ring (eq‐eq; eq=equatorial). The two rings of anabasine are close to a bisecting arrangement, with the observed conformations differing by an approximately 180° rotation of the pyridine subunit, denoted either syn or anti. The preference of anabasine for the eq‐eq‐syn conformation has been established by relative intensity measurements (syn/anti～5(2)). The conformational preferences of free anabasine are directed by a weak N???H? C hydrogen bond interaction between the nitrogen lone pair at piperidine and the closest C? H bond in pyridine, with N???H distances ranging from 2.686 (syn) to 2.667 Å (anti). Supporting ab initio calculations by using MP2 and the recent M05‐2X density functional are provided, evaluating the predictive performance of both methods.     

Total synthesis of phytoprostane F1 and its 16 epimer

The first synthesis of the two enantiomers of phytoprostane F₁ methyl ester 1 and 2 is described using the syn-anti-syn alcoxy ester 3 as starting material.     

Internal rotation and framework relaxation in ethene thiol

New and existing data on the ground and excited CS torsional states of the stable rotamers of ethene thiol have been analysed to give a potential function for internal rotation around the CS bond. The barrier between the syn and anti rotamers is found to be 800 cm^?1 and that at the planar anti conformation itself to be 12 cm^?1. the syn conformation is 50 cm^?2 more stable than the ‘quasi-planar’ anti conformation Satisfactory reproduction of the observed trends in rotational constants with torsional excitations has been achieved by introducing extensive relaxation of the CCS angle and the CS bond length during internal rotation. The CCS angle reduces by up to 5° v'hilst the CS bond length increases by up to 0.02 A during rotation from the syn to anti conformation. The use of ab initio M.O. calculations to provide an indication of the most significant aspects of structure relaxation is described.     

Structural,torsional, vibrational and response electric properties of 2,2′-bitellurophene rotamers. An ab initio and density functional theory investigation

The molecular structure, conformational behaviour, vibrational spectra and electronic (hyper)polarizabilities of tellurophene and 2,2′-bitellurophene rotamers were determined in gas by correlated ab initio and density functional theory calculations. The torsional potential for the rotation around the C²–C^2′ inter-ring bond shows two minima corresponding to anti-gauche and syn-gauche structures and three maxima to planar anti and syn forms and to perpendicular conformation. The potential energy curve is rather flat over the entire 0°–180° twisting range and free rotation cannot be excluded. The IR and Raman spectra of the gauche structures are rather similar to each other, vibrational transitions being scarcely helpful for an unambiguous identification of the rotamers. The dipole moment and the first-order hyperpolarizability increase on passing from the anti-gauche to the syn-gauche conformation by a factor of five and four, respectively. The second harmonic generation nonlinear optical process can be useful to identify the 2,2′-bitellurophene rotamers. On the other hand, the electronic polarizabilities of these structures are much more closer to each other, being predicted to be within 2–13 %.     

Factors that regulate the conformation of m-benziporphodimethene complexes: agostic metal-arene interaction, hydrogen bonding, and η2,π coordination

Group 12 and silver(I) tetramethyl‐m‐benziporphodimethene (TMBPDM) complexes with phenyl, methylbenzoate, or nitrophenyl groups as meso substituents were synthesized and fully characterized. The dimeric silver(I) complex displays an unusual η²,π coordination from the β‐pyrrolic C?C bond to the silver ion. All of the complexes displayed a close contact between the metal ion and the inner C(22)? H(22) on the m‐phenylene ring. The downfield chemical shifts of H(22) and large coupling constants between Cd^II and H(22) strongly support the presence of an agostic interaction between the metal ion and inner C(22)–H(22). Crystal structures revealed that the syn form is the predominant conformation for TMBPDM complexes. This is distinctively different from the exclusive anti conformation observed in m‐benziporphyrin and tetraphenyl‐m‐benziporphodimethene (TPBPDM) complexes. Evidently, intramolecular hydrogen‐bonding interactions between axial chloride and methyl groups stabilize syn conformations. Unlike the merely syn conformation observed in the solid‐state structures of TMBPDM complexes that contain an axial chloride, in solution these complexes display highly solvent‐ and temperature‐dependent syn/anti ratio changes. The observation of dynamic ¹H NMR spectroscopic scrambling between syn and anti conformations from the titration of chloride ion into the solution of the TMBPDM complex suggests that axial ligand exchange is a likely pathway for the conversion between syn and anti forms. Theoretical calculations revealed that intermolecular hydrogen‐bonding interactions between the axial chloride and CHCl₃ stabilizes the anti conformation, which explains the increased ratio for the anti form when dichloromethane or chloroform was used as the solvent.     

Trisphosphine‐Chelate‐Substituted Molybdenum and Tungsten Nitrosyl Hydrides as Highly Active Catalysts for Olefin Hydrogenations

Reaction of [M(NO)Cl₃(NCMe)₂] (M=Mo, W) with (iPr₂PCH₂CH₂)₂PPh (etpⁱp) at room temperature afforded the syn/anti‐[M(NO)Cl₃(mer‐etpⁱp)] complexes (M=Mo, a ; W, b ; 3 a,b (syn,anti); syn and anti refer to the relative position of Ph(etpⁱp) and NO). Reduction of 3 a,b (syn,anti) produced [M(NO)Cl₂(mer‐etpⁱp)] ( 4 a,b (syn)), [M(NO)Cl(NCMe)(mer‐etpⁱp)] ( 5 a,b (syn,anti)), and [M(NO)Cl(η²‐ethylene)(mer‐etpⁱp)] ( 6 a,b (syn,anti)) complexes. The hydrides [M(NO)H(η²‐ethylene)(mer‐etpⁱp)] ( 7 a,b (syn,anti)) were obtained from 6 a,b (syn,anti) using NaHBEt₃ (75 °C, THF) or LiBH₄ (80 °C, Et₃N), respectively. 7 a,b (syn,anti) were probed in olefin hydrogenations in the absence or presence of a hydrosilane/B(C₆F₅)₃ mixture. The 7 a,b (syn,anti)/Et₃SiH/B(C₆F₅)₃ co‐catalytic systems were highly active in various olefin hydrogenations (60 bar H₂, 140 °C), with maximum TOFs of 5250 h^?1 ( 7 a (syn,anti)) and 8200 h^?1 ( 7 b (syn,anti)) for 1‐hexene hydrogenation. The Et₃SiH/(B(C₆F₅)₃ co‐catalyst is anticipated to generate a [Et₃Si]⁺ cation attaching to the O_NO atom. This facilitates NO bending and accelerates catalysis by providing a vacant site. Inverse DKIE effects were observed for the 7 a (syn,anti)/Et₃SiH/(B(C₆F₅)₃ (k_H/k_D=0.55) and the 7 b (syn,anti)/Et₃SiH/(B(C₆F₅)₃ (k_H/k_D=0.65) co‐catalytic mixtures (20 bar H₂/D₂, 140 °C).     

Synthesis of 8-halogenated-7-deaza-2′-deoxyguanosine as an 8-oxo-2′-deoxyguanosine analogue and evaluation of its base pairing properties

8-Halogenated-7-deaza-2′-deoxyguanosines (8-halo-7-deaza-dG) were designed to structurally mimic 8-oxo-2′-deoxyguanosine (8-oxo-dG), which is representative of an oxidized nucleoside. It has been shown by NMR that the conformation around the N-glycosidic bond of (8-halo-7-deaza-dG) is preferably syn, similar to 8-oxo-dG. The base pairing properties of 8-halo-7-deaza-dG were studied by measuring the thermal denaturation temperature of the duplexes, showing that their base pair with dC is destabilized compared with natural dG. These results also support their preference for syn conformation. Unlike 8-oxo-dG, 8-halo-7-deaza-dG did not form a stable base pair with dA, most likely due to the lack of N7-H hydrogen bonding with dA. In conclusion, the newly-designed 8-halo-7-deaza-dG analogs resemble 8-oxo-dG in its shape and preference for syn conformation, but they do not form Hoogsteen base pair with the opposing dA.     

Oxonium ion-mediated synthesis of 4-substituted spiro-isoxazolines

The stereoselective synthesis of 4-bromo-spiro-isoxazolines was achieved in one step through the bromination of various isoxazoles that contain a pendant alcohol or carboxylic acid functional group. Isoxazole bromination leads to a bromonium ion intermediate, which opens either by neighboring oxygen lone pair electrons or by intramolecular nucleophilic attack. Single X-ray crystal data provide evidence that the two contiguous stereocenters of the spiro-isoxazoline are formed by the anti intramolecular attack of the nucleophile relative to bromine, since there is an anti stereochemical relationship between the spirocyclic ring oxygen and the bromine atom.     

Conformational preferences of the aldol adducts of oxadiazinones. H NMR spectroscopy and computational studies of N4-methyl and N4-isopropyloxadiazinones

The conformational properties of the aldol adducts of some N₄-isopropyl-oxadiazinones have been investigated by ¹H NMR spectroscopy and computational studies. An earlier study of the syn-aldol adducts of N₄-methyl-oxadiazinone 2 led to the conclusion that the solution and solid state conformation of these compounds involve syn-parallel arrangement of the C₂- and N₃-carbonyls of the oxadiazinones. However, the synthesis and asymmetric aldol reactions of an N₃-hydrocinnamoyl-N₄-isopropyl-oxadiazinone 4 has yielded aldol adducts 5a-e in which the orientation of the C₂- and N₃-carbonyls are most likely in the anti-parallel arrangement. These aldol adducts have been studied by ¹H NMR spectroscopy and the shielding aspect observed clearly suggests the presence of the anti-parallel arrangement. The installment of a N₄-d₆-isopropyl group further confirmed this assertion. Computational studies support the conclusion that solution state conformation of the N₄-methyl and N₄-isopropyl-oxadiazinones involves anti-parallel carbonyls in contrast to the solid state evidence of the X-ray crystallographic data of oxadiazinone 2.     

A theoretical study of carbazole dimers: Does carbazole form an excimer that undermines the performance of organic light emitting diodes?

Carbazole (Cz) dimers in various cofacial conformations, including staggered (Stg), anti, and syn, were explored by means of ab initio calculations at scaled opposite-spin (SOS)-MP2, SOS-CIS(D₀), and additional coupled cluster calculation levels. Similar to other π-conjugated molecules, strong Cz excimers form in the syn conformation in both S₁ and T₁ states, leading to significantly reduced optical excitation energies. Upon excitation, the dimers in the Stg and anti-conformations remain simple excited dimers, exhibiting similar optical energy gaps to those of the monomer. Being far more stable in the ground state, however, the Stg dimer is nearly isoenergetic to the syn dimer in the S₁ state and even more stable in the T₁ state. Given that the intermolecular interactions in the ground state are expected to govern the dimer conformations of Cz-based materials in the solid-state films of organic electronics, our results strongly demonstrate that the electronic excitation of Cz dimers do not necessarily lead to the strong excimer formation unless Cz molecules are forced to be arranged in the syn conformation.     

Quantum-chemical study of the relative stability of conformers of 1,4-dihydropyrazine and 1,4-dihydro-1,4-diphosphinine

Spatial and electronic structure of the molecules of 1,4-dihydropyrazine and 1,4-dihydro-1,4-dihydrophosphinine was studied by the non-empirical method G2. The boat conformation with the syn-orientation of the lone electron pairs was shown to be the most preferable form for both molecules.     

ss‐NMR and single‐crystal X‐ray diffraction in the elucidation of a new polymorph of bischalcone (1E,4E)‐1,5‐bis(4‐fluorophenyl)penta‐1,4‐dien‐3‐one

We report a new polymorph of (1E,4E)‐1,5‐bis(4‐fluorophenyl)penta‐1,4‐dien‐3‐one, C₁₇H₁₂F₂O. Contrary to the precedent literature polymorph with Z′ = 3, our polymorph has one half molecule in the asymmetric unit disordered over two 50% occupancy sites. Each site corresponds to one conformation around the single bond vicinal to the carbonyl group (so‐called anti or syn). The other half of the bischalcone is generated by twofold rotation symmetry, giving rise to two half‐occupied and overlapping molecules presenting both anti and syn conformations in their open chain. Such a disorder allows for distinct patterns of intermolecular C—H…O contacts involving the carbonyl and anti‐oriented β‐C—H groups, which is reflected in three ¹³C NMR chemical shifts for the carbonyl C atom. Here, we have also assessed the cytotoxicity of three symmetric bischalcones through their in vitro antitumour potential against three cancer cell lines. Cytotoxicity assays revealed that this biological property increases as halogen electronegativity increases.     

Sugar Puckering Drives G-Quadruplex Refolding: Implications for V-Shaped Loops

A DNA G-quadruplex adopting a (3+1) hybrid structure was modified in two adjacent syn positions of the antiparallel strand with anti-favoring 2′-deoxy-2′-fluoro-riboguanosine (^FrG) analogues. The two substitutions promoted a structural rearrangement to a topology with the 5′-terminal G residue located in the central tetrad and the two modified residues linked by a V-shaped zero-nucleotide loop. Strikingly, whereas a sugar pucker in the preferred north domain is found for both modified nucleotides, the ^FrG analogue preceding the V-loop is forced to adopt the unfavored syn conformation in the new quadruplex fold. Apparently, a preferred C3′-endo sugar pucker within the V-loop architecture outweighs the propensity of the ^FrG analogue to adopt an anti glycosidic conformation. Refolding into a V-loop topology is likewise observed for a sequence modified at corresponding positions with two riboguanosine substitutions. In contrast, 2′-F-arabinoguanosine analogues with their favored south-east sugar conformation do not support formation of the V-loop topology. Examination of known G-quadruplexes with a V-shaped loop highlights the critical role of the sugar conformation for this distinct structural motif.     

The conformation of succinic acid in aqueous solution studied by 1h and 13c nmr

The vicinal H-H coupling constants of succinic acid were obtained as a function of pH and related to its conformation. The syn-clinal arrangement of the two CO₂H groups appears as more stable than the anti-periplanar conformation at variance with previous work but in agreement with recent data on similar molecules. The vicinal¹³CO₂H-¹H coupling constant was also obtained and is found to support that conclusion. The analysis was extended to solvents of variable dielectric constant and no significant effect was found.