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C13H16N2O4, orthorhombic, P212121 (no. 19), a = 6.7876(2) Å, b = 8.8984(2) Å, c = 22.3399(6) Å, V = 1349.30(6) Å3, Z = 4, R gt(F) = 0.0384, wR ref(F 2) = 0.0947, T = 293(2) K.

The title mol­ecule is twisted about the methine-C—C(carbon­yl) bond [the O—C—C—O torsion angle is −20.8 (7)°] and the dihedral angle between the bromo­benzene and phenyl rings is 43.2 (2)°., The title compound, C15H13BrO2S, comprises three different substituents bound to a central (and chiral) methine-C atom, i.e. (4-bromo­phen­yl)sulfanyl, benzaldehyde and meth­oxy residues: crystal symmetry generates a racemic mixture. A twist in the mol­ecule is evident about the methine-C—C(carbon­yl) bond as evidenced by the O—C—C—O torsion angle of −20.8 (7)°. The dihedral angle between the bromo­benzene and phenyl rings is 43.2 (2)°, with the former disposed to lie over the oxygen atoms. The most prominent feature of the packing is the formation of helical supra­molecular chains as a result of methyl- and methine-C—H⋯O(carbon­yl) inter­actions. The chains assemble into a three-dimensional architecture without directional inter­actions between them. The nature of the weak points of contacts has been probed by a combination of Hirshfeld surface analysis, non-covalent inter­action plots and inter­action energy calculations. These point to the importance of weaker H⋯H and C—H⋯C inter­actions in the consolidation of the structure.

The conformational equilibrium of 2-[2′-(phenylselanyl)-acetyl]-5-methylfuran (1) and 2-[2′-(4′-sustituted-phenylsulfanyl)-acetyl]-5-substituted furans (2–7) was determined through the infrared (IR) analysis of the carbonyl stretching band (νCO) supported by M06–2X/aug-cc-pVDZ level of theory. Three stable conformations [sc(anti), ac(anti) and sc(syn)] were obtained in vacuum, with the sc(anti) the most stable for compound 1–6 and the ac(anti) for compound 7. The IR spectrain solution of n-C6H14, CCl4, CHCl3, CH2Cl2 and CH3CN show in general νCO doublets for compounds 2–6, with the exception of triplets in n-C6H14 for 2–4 and a symmetrical band in CHCl3 for 1, 3–6 and in CH2Cl2 and CH3CN for 1. The p-nitrophenyl compound 7 is insoluble in n-C6H14 and CCl4 and displays a doublet in all the other polar solvents. The PCM data allow to ascribe the sc(anti) conformer to the lowest frequency more intense νCO IR component and the sc(syn) one to the other doublet component for compounds 1–6, while the intermediary νCO frequency ac(anti) conformer, with negligible population, is assignedto the third triplet component predicted in n-C6H14 for compounds 2–4. Conversely, for compound 7, the more intense and lowest frequency νCOIR component was ascribed to the ac(anti), whereas the highest frequency one to the sum of the sc(anti) and sc(syn) populations. The conformational preferences of compounds 1–7 are governed by a balance between the orbital and the coulombic interactions estimated by means of natural bond orbitals (NBO), quantum theory of atoms in molecules (QTAIM), non covalent interaction (NCI) and short contacts analysis. While NBO delocalization energies indicate the ac(anti) conformer as the most stable for all compounds, NCI analysis reveals in the sc(anti) and sc(syn) conformers of compounds 1–6 an additional intramolecular stabilizing π‧‧‧π stacking interaction between the furyl and phenyl ring, which is counterbalanced in the sc(syn) conformer by the repulsive coulombic short contact between the carbonyl and furyl oxygen atoms. For compound 7, the ac(anti) conformer turns to be the most stable one as the electron withdrawing effect of the nitro substituent on the phenyl ring decreasesthe stabilizing π‧‧‧π stacking on the sc(anti) conformer.

A chiral methine-C atom connects the (4-chloro­phen­yl)sulfanyl, benzaldehyde and meth­oxy residues in the racemic title compound. Supra­molecular helical chains are formed in the crystal, being sustained by methyl- and methine-C—H⋯O(carbon­yl) inter­actions., The title compound, C15H13ClO2S, comprises (4-chloro­phen­yl)sulfanyl, benzaldehyde and meth­oxy residues linked at a chiral methine-C atom (the crystal is racemic). A twist in the methine-C—C(carbon­yl) bond [O—C—C—O torsion angle = 19.3 (7)°] leads to a dihedral angle of 22.2 (5)° between the benzaldehyde and methine+meth­oxy residues. The chloro­benzene ring is folded to lie over the O atoms, with the dihedral angle between the benzene rings being 42.9 (2)°. In the crystal, the carbonyl-O atom accepts two C—H⋯O inter­actions with methyl- and methine-C—H atoms being the donors. The result is an helical supra­molecular chain aligned along the c axis; chains pack with no directional inter­actions between them. An analysis of the Hirshfeld surface points to the important contributions of weak H⋯H and C⋯C contacts to the mol­ecular packing.

A conformational study of some 2-[2’-(4′-substituted-phenylsulfinyl)-acetyl]-5-methylfurans 1 – 4 (OMe 1, Me 2 , H 3 , Cl 4 ) was performed using IR carbonyl stretching and analysis supported by Natural Bond Orbital (NBO) and Polarisable Continuum Model (PCM) calculations at the B3LYP-D3/aug-cc-pVDZ level, and X-ray diffraction (for 2 and 4 ). The computational results indicated the existence of four stable conformations with variable degrees of folding (stacking) between the phenyl and the furanyl rings, in the following order of stability: sc ( anti ) 1 ≫ ac ( syn) > sc ( anti ) 2 > sc ( syn ). The PCM data showed that the mean abundance of the most stable lowest frequency sc ( anti ) 1 conformer in vacuum decreases progressively as the solvent permittivity increases, and, concomitantly, the population of the highest ν CO frequency sc ( anti ) 2 conformer increases in the same direction. Close inspection to the PCM ν CO frequencies and populations of the sc ( syn ) and ac ( syn ) conformers suggests that their IR lines should be missed due to their low intensities or hidden under the intense lowest ν CO component of the sc ( anti ) 1 conformer. The IR experimental trend observed for the components of the doublet carbonyl band in all solvents just matches the computational results and allows ascribing the most intense lowest ν CO frequency and the least intense highest ν CO frequency components in CCl 4 , to the sc ( anti ) 1 and sc ( anti ) 2 conformers, respectively. The appropriate S δ+ (4) … O δ– (1) short contacts stabilise the four conformers to different extents, while the quasi -parallel C δ+ = O δ– and S δ+ = O δ– dipole orientations strongly destabilise electrostatically only the sc ( anti ) 2 conformer. This Repulsive Field Effect is also responsible for the increase in its ν CO stretching frequency with respect to the other conformers. The suitable β and γ dihedral angles of the anti conformers favour the close proximity of the centroids of the furan and the phenyl rings and the stabilising O (9)[furan] … C (10) [phenyl] short contacts. In contrast, the appropriate geometry adopted by the ac ( syn ) conformer gives rise to the O δ– (26) … H δ+ (18) short contact and the LP O(26) →σ* C6 – H18 orbital delocalisation (hydrogen bond), which significantly stabilise this conformer with respect to the sc ( syn ) form. The sum of the delocalisation energies in the NBO analysis does not match the calculated stability of the four conformers for series 1 – 4 . The closeness of the mean delocalisation energy values found for all the conformers suggests that the computed order of stability is controlled mainly by the relevant short contacts and the coulombic repulsions between the negatively charged carbonyl, sulfinyl and furyl oxygen atoms. In particular, the strong electrostatic short contact O δ– (CO) … O δ– (SO) repulsion and the half as intense O δ– (CO) … O δ– (fur) repulsion destabilise to different extents the sc ( anti ) 2 and the pair of syn conformers, respectively. Therefore, the calculated order of stability of the four conformers for 1 – 4 results from the overall balance of the orbital and electrostatic interactions. X-ray single crystal analysis of 2 and 4 revealed that the molecules assume an unfolded (stretched) geometry with a sc ( syn ) conformation, and that they are stabilised through centrosymmetrical C–H ( o -Ph) …. O (co) and C–H ( m -Ph) …. Cg 1(fur) interactions (for 2 ) and C–H ( o -Ph) … O (co) and C Ph –Cl … Cg 2(Ph) interactions (for 4 ).

The conformational analysis of some 2‑(methoxy)‑2‑[(4‑substituted)‑phenylsulfanyl]‑(4'‑substituted) acetophenones was performed through infrared (IR) spectroscopic analysis of the carbonyl stretching band (νCO), supported by B3LYP/6-31+G(d,p) calculations and X-ray diffraction. Five (1-5) of the seven studied compounds (1-7) presented Fermi resonance (FR) on the νCO fundamental transition band. Deuteration of these compounds (1a-5a) precluded the occurrence of FR, revealing a νCO doublet for all compounds in all solvents used. The computational results indicated the existence of three conformers (c1, c2 and c3) for the whole series whose relative abundances varied with solvent permittivity. The higher νCO frequency c1 conformer was assigned to the higher frequency component of the carbonyl doublet, while both c2 and c3 were assigned to the lower frequency one. Anharmonic vibrational frequencies and Potential Energy Distribution (PED) calculations of compound 3 indicated that the combination band (cb) between the methyne δCH and one skeletal mode couples with the νCO mode giving rise to the FR on the c2 conformer in vacuum and on the c1 one in non-polar solvents. The experimental data indicated a progressive increase in c1 conformer stability with the increase of the solvent dielectric constant, which is in good agreement with the polarizable continuum model (PCM) calculations. The higher νCO frequency and the stronger solvation of the c1 conformer is a consequence of the repulsive field effect (RFE) originated by the alignment and closeness of the Cδ+Oδ- and Cδ+Oδ- dipoles. Finally, the balance between orbital and electrostatic interactions dictates the conformational preferences. X-ray single crystal analysis for compound 6 revealed the c1 geometry in the solid state and its stabilization by CH…O hydrogen bonds.

An analysis of carbonyl bands in the infrared spectra of some 2-ethylsulfonyl 4′-substituted phenylacetates bearing substituents NO2 (1), H (2) and OMe (3), supported by B3LYP/6-31G(d,p) and SM5.42R at PM3 level calculations, along with natural bond orbital analysis (NBO) and X-ray diffraction (for 1) was performed. Theoretical data indicated the existence of two stable gauche conformations (g 1 and g 2). The g 1 conformer is the most stable, least polar and has the lowest νCO frequency. The more intense, lower frequency carbonyl doublet component found in CCl4 solution is assigned to the g 1 conformer. As the solvent dielectric constant increases (going from CCl4 to MeCN) the higher frequency νCO doublet increases in intensity. This behaviour is reproduced by the solvation free energy calculations, supporting the conformer assignments. NBO calculations indicate that the most important orbital interaction is LPO9 → π*C7=O8 for both conformers, which corresponds to [C=O ↔ C+–O-] conjugation. This stabilises the g 1 conformer to a greater extent and is responsible for the lower νCO frequency. The sum of the selected NBO delocalisation energies for 1–3 indicates that the g 1 conformer is more stable. It is concluded that the calculated greater stability of the g 1 conformer is due to a balance of attractive electrostatic and orbital interactions along with relevant hydrogen bonds. The X-ray crystal structure analysis of 1 shows the presence of two crystallographic independent but almost superimposable molecules each which adopt a cis geometry. The molecules are consolidated into the three-dimensional crystal packing by C–H…O interactions as well as by nitro- N–O…π(phenyl) contacts.

The X-ray single crystal analysis of isomeric ortho, meta, and para bromo-substituted α-methylsulfonyl-α-diethoxyphosphoryl acetophenones showed that this class of compound adopts synclinal (gauche) conformations for both [-P(O)(OEt)2] and [-S(O)2Me] groups, with respect to the carbonyl functional group. The phosphonate, sulfonyl, and carbonyl functional groups are joined through an intramolecular network of attractive interactions, as detected by molecular orbital calculations at the M06-2X/6-31G(d,p) level. These interactions are responsible for the more stable conformations in the gas phase, which also persist in the solid-state structures. The main structural distinction in the title compounds relates to the torsion angle of the aryl group (with respect to the carbonyl group), which gives rise to different interactions in the crystal packing, due to the different positions of the Br atom.

The conformational analysis of some 4'-substituted 2-(phenylselanyl)-2-(ethylsulfanyl)-acetophenones bearing the substituents NO2 (1), Br (2), H (3), Me (4) and OMe (5) was performed by ν(CO) IR analysis, B3LYP/6-31+G(d,p) and single point polarisable continuum model (PCM) calculations, along with NBO analysis for 1, 3 and 5. Calculations for 1-5 indicate the existence of three stable conformations, c1, c2 and c3, whose stability depends on the balance between electrostatic and orbital interactions that are strictly related to the geometrical arrangement. The comparison between the experimental IR spectra in solution and the computed data in gas phase for 1-5 allows the c1 conformer to be assigned to the less intense component at higher frequency of the carbonyl doublet and both the c2 and c3 ones to the more intense lower frequency component. The sum of the calculated molar fraction of c2 and c3 conformers decreases from 95% to 63% on going from 1 to 5 (in gas phase), and this trend compares well with the PCM calculations and the IR experimental data for the majority of the solvents for all compounds 1-5. The NBO analysis for 1, 3 and 5 shows that the sum of the relevant orbital delocalization energies for the c1, c2 and c3 conformers is almost constant and does not match the computed stability order. The lowest stability of the c1 conformer for 1-3 can be related to the small value of the α dihedral angle that enables a strong electrostatic destabilizing repulsion between the O(CO)(δ-)…S(δ-) atoms. The relative stability of the c1 conformer increases for 4 and 5 as the α dihedral angle enlarges and the repulsion is minimized. Moreover, the strong repulsive field effect between the C(δ+)=O(δ-) and C(δ+)-S(δ-) dipoles exerted to a greater extent on the c1 conformers of 1-3 with respect to 4 and 5, causes a major increase of the corresponding C=O bond orders and related carbonyl frequencies. For the c2 conformer, the electrostatic destabilizing repulsion between the O(δ-)…Se(δ-) atoms is weaker than that involving the O(δ-)…S(δ-) atoms in the c1 conformer and therefore has negligible effects on the conformer stability that is mainly determined by the sum of the orbital interactions. The c3 conformer has the shortest S(δ-)…Se(δ-) contact for all compounds and thus the related electrostatic repulsion seems to be the most important factor that affects its stability. In conclusion, the computed order of stability of the three conformers for 1-5 depends on the electrostatic repulsions between close charged atoms rather than on the sum of the orbital delocalization energies that are quite similar for all the conformers.

A conformational study of some 4′-substituited 2-(phenylselanyl)-2-(methoxy)-acetophenones (OMe 1, H 2, and Cl 3) was performed using IR carbonyl stretching band analysis supported by NBO and PCM calculations at the B3LYP/6-31 + G (d,p) level for 1–3 and using X-ray diffraction for 1 and 2. The computational results indicated the existence of three stable conformers for the series (c2, c3, and c1 in order of decreasing stability), whose relative abundance changes with solvent permittivity. The experimental trend observed for the components of the triplet carbonyl band in all solvents matches well with computational results and thus allows for their assignment to distinct conformers. The relative population of the c1 conformer increases in more polar solvents, becoming the most stable conformer in the highest permittivity solvent, acetonitrile, as indicated by IR spectra and PCM calculations. These findings are related to the quasi parallel geometry assumed by the Cδ+ = Oδ− and Cδ+-Oδ- dipoles, which favour stronger solvation. NBO analysis shows that the sum of the energies (ΣE) of the relevant orbital interactions stabilizes the c3 conformer of 1–3 slightly, likely due to the minor contribution of the LPO5→σ*C3 Se10 interaction. However, only the c1 conformer is significantly destabilized by the Oδ−(1)CO … Oδ−(5)OMe short contact electrostatic repulsion, which is also responsible for its highest νCO frequency. In addition, the LPO5→ σ*C2 C3 orbital interaction accounts for the lowest νCO frequency of c3 conformer. X-ray single crystal analysis of compounds 1 and 2 indicates that in the solid state they assume the least stable c1 conformation found in the gas phase. Molecules of these compounds are stabilized in the crystal through a series of C H⋯O and C H … π intermolecular interactions.

The conformational study of some 2-(2′-haloacetyl)-5-substituted five-membered heteroaromatic compounds Z-CH 2 C(O)(C 4 H 2 X) Y bearing a halogen (Z = Cl or Br) at the 2′-position and (Y = NO 2 , H, Me or Cl) substituents at the 5-position of the heteroaromatic ring for X = NMe, O and S was performed by IR carbonyl stretching band (ν CO ) analysis supported by the harmonic frequency, NBO and PCM calculations on the minima and saddle-point structures obtained at the M05-2X/aug-cc-pVTZ level. The computational results predicted the presence of four stable conformers, classified by the orientation of the X ring –C C O ( syn / anti ) and the O C C–Z ( anticlinal / synperiplanar ) moieties as ac ( syn ), sp ( syn ), ac ( anti ) and sp ( anti ). The anti / syn equilibrium controls the relative stabilities of the conformers to a large extent while the anticlinal / synperiplanar accounts for the observed trend of the IR carbonyl band components. The computed ν CO frequencies and the PCM trend of the relative abundance in solvents of increasing permittivity allowed the pairs of ac ( syn )/ ac ( anti ) and sp ( syn )/ sp ( anti ) conformers to be assigned to the lower and higher ν CO frequency IR carbonyl doublet components, respectively. The PCM data failed to reproduce the experimental carbonyl triplet found in chloroform. However, the additional component could be justified by assuming the formation of complexes constituted by one chloroform molecule hydrogen bonded to the conformers in a PCM chloroform continuum. The NBO and short contact analysis suggested that the syn / anti conformational equilibrium is governed mainly by electrostatic interactions, while the anticlinal / synperiplanar depends to different extents on both orbital and electrostatic interactions.

The analysis of the IR carbonyl band of some 3,3-bis[(4′-substituted phenylsulfanyl)]1-methyl-2-piperidinones 1–5 bearing as substituents OMe 1, Me 2, H 3, Cl 4 and Br 5, supported by B3LYP/6-31G(d,p) calculations for 3, indicated the existence of three conformers in the gas phase and practically a single conformer in solution. In the gas phase, the c1 conformer is less polar and slightly more stable than the most polar c2 conformer. The c3 conformer is the least polar and least stable conformer. The summing up of the selected natural bond orbital delocalization orbital energies is practically the same (ca.136 kcal mol−1) for the c1, c2 and c3 conformers of 3. Therefore, the trend of the [O δ−_(CO)···H δ+o− Ph] (hydrogen bond) attractive electrostatic interactions along with the trend of the [O δ−_(CO)···S δ−] repulsive electrostatic interactions are the main factors which determine the observed computed relative populations for the c1 (44%), c2 (31%) and c3 (25%) conformers. Moreover, the IR single carbo...

Infrared carbonyl band analysis, supported by B3LYP/6-31 + G(d,p) and single-point PCM calculations, natural bond orbital (NBO) analysis and X-ray diffraction (XRD) were carried out for the diastereoisomers of a selection of 4′-substituted 2-(phenylselanyl)-2-(ethylsulfinyl)-acetophenones bearing the substituents NO2 1a, Br 2a, H 3a, Me 4a and OMe 5a for the CRSR/CSSS enantiomeric pair and Br 2b and Me 4b for the CRSS/CSSR pair. The theoretical data indicated the existence of three stable conformations for the CRSR series and two for the CRSS series. For both series, the single-point PCM calculations showed that the relative abundance of the less stable conformers in the gas phase progressively increases as the dielectric constant of the media increases. For compounds 1a–5a, the balance between the electrostatic and orbital interactions controls the calculated stability, as well as the νCO frequency order. Conversely, the more stable conformer in the 2b and 4b compounds is mainly stabilised by the additional orbital interactions LP(S) → σ*C-Se, LPO(S-O) → σ*C-H(CH2Me) and LPO(S-O) → σ*C-H(o-PhSe). The XRD analysis indicates that the major component of 3a (CRSR) matches the geometry of the intermediate stable c2 conformer. Similarly, the solid-state structure of 2b (CRSS) corresponds to the less stable c2 conformer. The molecules in the solid are linked in centrosymmetrical pairs through π … π interactions between Se-bound phenyl rings, along with phenyl-C H…O (carbonyl and sulphinyl) interactions.

Increased diastereoisomeric excesses are obtained for the sulfanylation reactions of some 2-methylsulfinyl cyclanones under phase-transfer catalysis using the chiral catalyst QUIBEC instead of TEBA. The optically pure (SS,2S)-2-methylsulfinyl-2-methylsulfanylcyclohexanone thus prepared reacts with ethyl acetate lithium enolate affording, after hydrolysis, (R)-2-[(ethoxycarbonyl)methyl]-2-hydroxycyclohexanone in 60% ee. Density functional theory calculations (at the B3LYP/6-311++G(d,p) level) can successfully explain the origin of this result as the kinetically favored axial attack of the nucleophile to the carbonyl group of the most stable conformer of the cyclanone, in which the CH3SO and CH3S groups are at the equatorial and axial positions, respectively.

The analysis of the IR carbonyl band of the 2-substituted N -methoxy- N -methylacetamides Y–CH 2 C(O)N(OMe)Me (Y = F 1 , OMe 2 , OPh 3 , Cl 4 ), supported by B3LYP/6-311++G(3df, 3pd) calculations along with the NBO analysis for 1 – 4 , indicated the existence of cis – gauche conformers i.e. ( c ) and ( g ) for 1 and 3 , ( c 1 , c 2 ) and ( g 1 , g 2 ) for 2 , and ( c ) and ( g 1 , g 2 ) for 4 . In the gas phase, the g conformer population prevails over the c one, for 1 and 3 , the ( c 1 + c 2 ) population prevails over the ( g 1 + g 2 ) one for 2 , and the ( g 1 + g 2 ) conformer population is more abundant than ( c ) one for 4 . In n -hexane solution, the cis conformer is more abundant for 1 – 3 . The occurrence of Fermi resonance in the ν CO region, in n -hexane, precludes the estimative of relative populations of the ( c , g 1 , g 2 ) conformers for 4 . The SCI-PCM calculations agree with the solvent effect on the ν CO band component relative intensities for 1 – 3 . NBO analysis showed that the n N → π co ∗ orbital interaction is the main factor which stabilizes the gauche ( g , g 1 , g 2 ) conformers for 1 – 4 into a larger extent relative to the cis ( c , c 1 , c 2 ) ones. The n Y → π co ∗ , σ C Y → π co ∗ , π co → σ C Y ∗ and π co ∗ → σ C Y ∗ orbital interactions still contribute, but into a minor extent for the stabilization of the gauche conformers relative to the cis ones. The existence of some pyramidalization at the nitrogen atom of the Weinreb amides 1 – 4 is responsible for the occurrence of Y δ − (4)···O δ − (9) and Y δ − (4)···N δ − (7) short contacts in the gauche ( g , g 1 , g 2 ) conformers, which originates strong repulsive Coulombic interactions, acting in opposition to the large orbital stabilization of the gauche conformer with respect to the cis one. Therefore, a delicate balance of the Coulombic and orbital interactions seems to be responsible for the observed stabilization of the gauche ( g , g 1 , g 2 ) and cis ( c , c 1 , c 2 ) conformers, both in the gas phase and in the solution for 1 – 4 . However, the cis conformer predominance, in non polar solvents, for the 2-substituted N -methoxy- N -methyl acetamides 1 – 3 , bearing in α first raw (fluorine and oxygen) atoms, is in the opposite direction to the gauche conformer preference for the corresponding 2-substituted N , N -dialkyl-acetamides.

The analysis of the IR carbonyl band of the N -methoxy- N -methyl-2-[(4′-substituted)phenylsulfonyl]propanamides Y-PhSO 2 CH(Me)C(O)N(OMe)Me (Y = OMe 1 , Me 2 , H 3 , Cl 4 , NO 2 5 ), supported by HF/6-31G(d,p) calculations of 3 , indicated the existence of two gauche conformers ( g 1 and g 2 ), the g 1 conformer being the most stable and the least polar one (in gas phase and in solution). Both conformers are present in solution of the non polar solvent (CCl 4 ) for 1 – 5 and in solution of the more polar solvents (CHCl 3 ) for 1 , 4 , 5 and (CH 2 Cl 2 ) for 5 , while only the g 1 conformer is present in solution of the most polar solvent (CH 3 CN) for 1 – 5 . The g 1 and g 2 conformers correspond to the enantiomeric pairs of diastereomers ( diast 1 and diast 2 ) whose relative configurations are [C(3) R N R ]/[C(3) S N S ] and [C(3) R N S ]/[C(3) S N R ], respectively. The computed carbonyl frequencies for g 1 ( diast 1 ) and g 2 ( diast 2 ) stereoisomers of 3 match well the experimental values. The NBO analysis, for 3 shows the important role of the orbital interactions in conformer stabilization and the overall balance of these interactions corroborates that the g 1 conformer is more stable than the g 2 one. The observed abnormal solvent effect on the relative intensities of the carbonyl doublet components is attributed to the molecular crowding in the g 2 conformer which hinders its solvation in comparison to the g 1 conformer ( diast 1 ). X-ray single crystal analysis performed for 3 shows the existence of two g 2 a and g 1 b conformers of diastereomers ( diast 2 a and diast 1 b ) whose absolute configurations are [C(3) R N S ] and [C(3) R N R ], respectively. The larger population and, thus, the larger stabilization of the g 2 a conformer over the g 1 b form in the crystals may be associated with a larger energy gain deriving from dipole moment coupling in the former conformer along with a series of C H…O electrostatic and hydrogen bond interactions.

The analysis of the IR carbonyl band of the N -methoxy- N -methyl-2-[(4′-substituted)phenylthio]propanamides Y-PhSCH(Me)C(O)N(OMe)Me (Y=OMe 1 , Me 2 , H 3 , Cl 4 , NO 2 5 ), supported by B3LYP/cc-pVDZ calculations of 3 , indicated the existence of two gauche conformers ( g 1 and g 2 ), the g 1 conformer being the more stable and the less polar one (in gas phase and in solution). Both conformers are present in solution of the polar solvents (CH 2 Cl 2 and CH 3 CN) for 1 – 5 and in solution of the less polar solvent (CHCl 3 ) for 1 – 4 , while only the g 1 conformer is present in solution of non polar solvents ( n -C 6 H 14 and CCl 4 ) and in solution of CHCl 3 for 5 . NBO analysis shows that both the σ C S → π C O ∗ (hyperconjugative) and the π C O → σ C - S ∗ orbital interactions contribute almost to the same extent for the stabilization of g 1 and g 2 conformers. The π C O ∗ → σ C S ∗ , n s → π C O ∗ and the n s → π C O ∗ orbital interactions stabilize more the g 1 conformer than the g 2 one. Moreover, the suitable geometry of the g 1 conformer leads to its stabilization through the LP O 2 → σ C 8 H 11 ∗ orbital interaction (hydrogen bond) along with the strong O [ CO ] δ - … H [ O - Ph ] δ + electrostatic interaction. On the other hand, the appropriate geometry of the g 2 conformer leads to its stabilization by the LP O 22 → σ C 9 H 13 ∗ orbital interaction (hydrogen bond) along with the weak O [ OMe ] δ - … H [ o ′ - Ph ] δ + electrostatic interaction. As for the 4′-nitro derivative 5 the ortho -phenyl hydrogen atom becomes more acidic, leading to a stronger O [ CO ] δ - … H [ o - Ph ] δ + interaction and, thus, into a larger stabilization of the g 1 conformer in the whole series. This trend is responsible for the unique IR carbonyl band in CHCl 3 solution of 5 . The larger occupancy of the π C O ∗ orbital of the g 1 conformer relative to that of the g 2 conformer, along with the O [ CO ] δ - … H [ o - Ph ] δ + electrostatic interaction (hydrogen bond) justifies the lower carbonyl frequency of the g 1 conformer with respect to the g 2 one, in gas phase and in solution.

The analysis of the IR carbonyl band of the α-methylsulfonyl-α-diethoxyphosphoryl p -substituted acetophenones p -Y-Ph-C(O)CH(SO 2 Me)[P(O)(OEt) 2 ] (Y = OMe 1 , H 2 , F 3 , Cl 4 , Br 5 and NO 2 6 ) supported by HF/6-31G(d,p) ab initio calculations of the α-methylsulfonyl-α-diethoxyphosphoryl acetophenone 2 , indicated the existence of a single stable c 1 conformer in gas phase and in solvents of increasing polarity, along with the presence of second less stable conformation in gas phase. The c 1 conformer present the (SO 2 Me) group and the [P(O)(OEt 2 )] groups in a syn-clinal (gauche) geometry and is stabilised through of the O δ− (CO) ...P δ+ (PO) , O δ− [PO(OEt)] ...C δ+ (CO) , O δ− (PO) …C δ+ (CO) , O δ− (CO) …S δ+ (SO2Me) and O δ− (SO2) ...C δ+ (CO) electronic interactions along with H δ+ (SO2Me) …. O δ− (CO) , H δ+ (CH2)[POEt] …. O δ− (SO2Me) , H δ+ (o-Ph) …. O δ− (CO) and H δ+ (o′-Ph) …. O δ− (PO) intramolecular hydrogen bonds. The almost constant negative carbonyl frequency shifts (Δ ν ) for the title compounds 1 – 6 with respect to the parent acetophenones 7 – 14 corroborates the prevalence of the electronic interactions over the − I σ inductive effect of the α -substituents for the title compounds and gives strong support for the existence of the crossed O δ− (CO) …S δ+ (SO2Me) and O δ− (SO2) ...C δ+ (CO) (charge transfer and electrostatic); O δ− (CO) ...P δ+ (PO) and O δ− [PO(OEt)] ...C δ+ (CO) , (electrostatic) interactions.

The 1H NMR spectra of N-methoxy-N-methyl-2-[(4′-substituted)phenylsulfinyl]-propanamides [Y-Ph-S(O)CH(Me)C(O)N(OMe)Me; Y = OMe 1, Me 2, H 3, Cl 4, NO2 5] along with the X-ray diffraction analysis of the nitro-derivative (5), have shown the existence of two pairs of diastereomers (racemic mixture) [CRSS/CSSR (diast1) and CRSR/CSSS (diast2)] in the ratio of ca. 7:3, respectively. The νCO IR analysis of the title compounds supported by HF and B3LYP/6-31G∗∗ calculations of 3 and of the parent N-methoxy-N-methyl-propanamide (6) by HF, have shown that diast1 exists in an equilibrium between the two more polar and more stable quasi-cis (q-c1 and q-c2) conformers and the gauche(g) conformer. The population of the g conformer in the equilibrium increases with the increase in the solvent polarity, which is attributed to a larger solvation effect on the carbonyl and sulfinyl groups. Diast2 of compound 3 occurs in the gas phase as an equilibrium between the most stable quasi-gauche (q-g) conformer and the quasi-cis (q-c) conformer, both presenting very similar dipole moments. The former is stabilized by electrostatic and charge transfer interactions, which results in a less solvated spatial arrangement. Moreover, all conformers of both diastereomers are stabilized by several intramolecular hydrogen bonds. X-ray single crystal analysis performed for diast1 and for diast2 of 5 indicates that both stereoisomers assume, in the solid state, the anti-clinal (gauche) conformation. For the crystal packing, diast1 of 5 is made up of three molecules joined through two centro-symmetric H...O hydrogen bonds.

The analysis of the infrared carbonyl bands of some 2-ethylsulfinyl-(4′-substituted)-phenylacetates bearing the substituents NO 2 ( 1 ), Cl( 2 ), Br( 3 ), H( 4 ), Me( 5 ) and OMe( 6 ), along with B3LYP/6-31G(d,p), SM5.42R solvation model calculations and natural bond orbital (NBO) analysis was carried out. Theoretical data indicated the existence in the gas phase of three stable gauche conformers, whose relative abundances in condensed phase change at different extent in the series 1 – 6 , depending on the solvent permittivity. The comparison between the IR spectra in solvents of increasing permittivity (from CCl 4 to CH 3 CN) and the calculated SM5.42R data in solution allows a precise assignment of the experimental band components to the distinct conformers. The sum of the main relevant NBO orbital interactions energies does not match the calculated B3LYP relative energies of the three stable conformers of 1 – 6 in the gas phase. On the contrary, the short contact analysis indicates that the electrostatic interactions largely control their relative stability and play a basic role to determine the calculated ν CO frequencies order. Moreover, as these contacts dictate the specific geometry assumed by each conformer, the electrostatic interactions determine their different solvation properties too, thus accounting for the experimental stability observed in solution.

The analysis of the IR carbonyl band of the α-methylthio-α-diethoxyphosphoryl p-substituted acetophenones p-Y-Ph-C(O)CH[SMe][P(O)(OEt)2] (Y = OMe 1, H 2, F 3, Cl 4, Br 5 and NO2 6), supported by HF/6-31G** ab initio calculations of the α-methylthio-α-diethoxyphosphoryl acetophenone 2, indicated the existence of a single stable c1 conformer in gas phase and in solvents of increasing polarity, along with the presence of a second high energy conformation in gas phase. The c1 conformer presents the (SMe) group in a syn-clinal (gauche) geometry and the [P(O)(OEt2)] group in a quasi-periplanar (quasi-cis) geometry with respect to the carbonyl group, which is stabilized by the synergism of the nS/π*CO and σC–S/π*CO orbital interactions and O δ − ( PO ) ⋯ C δ + ( CO ) orbital and Coulombic interactions, acting to increase the carbonyl oxygen negative charge, and in turn facilitates the O δ − ( CO ) ⋯ P δ + ( PO ) electrostatic interaction. The negative and almost constant carbonyl frequency shifts (Δν) of ca. −11 cm−1 for compounds 1–6 relative to the parent acetophenones 7–12, in CCl4, corroborate the prevalence of the electronic interactions over the (−Iσ) inductive effect of the α-substituents for the title compounds. The X-ray diffraction analysis for 3 indicates that it exists in the solid state in the c 1 ′ conformation, which is stabilized by the intramolecular Oδ−(1)[CO}⋯ Pδ+(5)[PO] and Hδ+(10)[SMe]⋯Oδ−(6)[PO] orbital and electrostatic (hydrogen bond) interactions. Moreover, these molecules form dimers which are stabilized through intermolecular hydrogen bonds Hδ+(4)[CH]⋯Oδ−(1)[CO], Hδ+(5′)[Ph]⋯ Oδ−(6)[PO] and Hδ+(6′)[Ph]⋯ Oδ−(6)[PO].

C10H12N2O2, M r = 191.21, P21, a = 5.5771(7), b = 27.841(3), c = 6.906(1) Å, β = 111.937(9)°, Z = 4, R 1 = 0.0462. The two independent molecules in the asymmetric unit are linked through two very strong quasi centro-symmetric hydrogen bonds. The oxadiazinone rings, of both molecules, show the pyramidal inversion at N-4 nitrogen, thus resulting in a C(R)N(S)—C(R)N(R) diastereomeric pair. The analysis of the IR N-H stretching band (in the solid and in carbon tetrachloride solution) and the 13C NMR experiment at low temperature are in agreement with the X-ray crystal structure.

The IR and 1 H NMR spectra analyses of some meta - (Y=OMe 1 , Me 2 , F 3 , Cl 4 , Br 5 and NO 2 6 ) and para - (Y=OMe 7 , H 8 , F 9 , Cl 10 , Br 11 and NO 2 12 ) substituted α-methylsulfinyl-α-diethoxyphosphorylacetophenones m,p -YPhC(O)C*H[S*(O)Me][P(O)(OEt) 2 ], along with theoretical calculations at the B3LYP/6-31+g(d,p) level, for compound 8 , have shown, in solution of solvents of increasing polarity and in the gas phase, the existence of two enantiomeric pairs (racemic mixtures). The more stable and less polar (C S S S ; C R S R ) enantiomeric pair (conformer pair I ) display the [MeS(O)] group in a quasi-periplanar ( quasi-cis ) geometry and the [P(O)(OEt) 2 ] group in a anti-clinal ( gauche ) geometry relative to the carbonyl group. The less stable and more polar (C R S S ; C S S R ) enantiomeric pair (conformer pair II ) presents both substituents in a syn-clinal ( gauche ) geometry. The observed solvent effect on the IR ν CO doublet components and on the two 1 H NMR methyl signals relative intensities, for the whole series along with the complete deuterium exchange of the α-methine hydrogen atom of 1 , strongly indicate that both pairs of diastereomers [(C S S S ; C R S R ) and (C R S S ; C S S R )] are equilibrated in solution through an intermediate enolic form. The more stable (C S S S ; C R S R ) enantiomeric pair [conformer pair ( I )] is strongly stabilised by O (CO) δ− ⋯S (SO) δ+ charge transfer and electrostatic interaction, while the remaining electronic interactions are almost counterbalanced among themselves, and are important in the stabilisation of the less stable (C R S S ; C S S R ) enantiomeric pair [conformer pair ( II )]. Compound 1 , in the solid state, occurs as the (C R S S ; C S S R ) enantiomeric pair [conformer pair ( II ′)], as determined by X-ray diffraction analysis, whose geometry is similar to conformer pair ( II ), found in gas phase. The O (CO) δ− ⋯S (SO) δ+ , O (POEt) δ− ⋯C (CO) δ+ , O (POEt) δ− ⋯S (SO) δ+ and H (o-Ph) δ+ ⋯O (CO) δ− intramolecular interactions contribute for the stabilisation of conformer pair ( II ′) in the solid. Further stabilisation derives from dipole moment couplings and by an intricate network of electrostatic interactions (hydrogen bonds).

The existence of the keto–enol equilibrium in diluted solutions of ortho-substituted α-methylthio-α-diethoxyphosphorylacetophenones X-PhC(O)CH[SMe][P(O)(OEt)2] (X=OMe 1, Me 2, F 3, Cl 4 and Br 5) has been detected through IR (νOH, νCO and νPO) and NMR (1H, 13C and 31P) analyses. The enol form exists as a strong intramolecular hydrogen bonded ‘conjugated chelate’. For compounds 1 and 3 for which the ortho-OMe and F substituents are almost coplanar with respect to the CO group, their strong +M effect gives rise to a strong πX–πPhC(O) conjugation, which hinders the enolization of the α-methine hydrogen atom (circa ∼4% for the enol form). Similarly, the weaker πCH3–πPhC(O) hyperconjugative effect of the coplanar o-Me-PhC(O) moiety, in compound 2, is responsible for a slightly larger amount of the enol form (circa ∼22%), while for 4 and 5, the Cl and Br substituents lead to deviation from planarity in relation to the CO group and only the strong −I effect plays a significant role, being responsible for the presence of larger amounts of the enol form (>50%).

The preferred conformations of p-substituted α-bromo-α-ethylsulfonylacetophenones Y–PhC(O)CH(Br)SO2Et (Y=OMe 1, Me 2, H 3, Cl 4, Br 5, CN 6 and NO2 7) are determined by νCO IR analysis; HF/6-31G** ab initio computations and X-ray diffraction (for 3). In the gas phase, compound 3 shows the existence of two stable conformers. The more stable and more polar c1 conformer presents the α-ethylsulfonyl and the α-bromo substituents in syn-periplanar (quasi-cis) and syn-clinal (gauche) geometries, respectively, with respect to the carbonyl group. For the second, less stable and less polar, c2 conformer, both the α substituents assume a syn-clinal (gauche) geometry. The larger stabilisation of the c1 conformer relative to c2, in the gas phase, is attributed to the summing up of the nBr/π∗CO and σC–Br/π∗CO hyperconjugative interactions and OCOδ−⋯SSO2δ+, HCH2[SO2Et]⋯OCOδ− and OSO2δ−⋯CCOδ+ orbital and electrostatic interactions, which are stronger for the c1 conformer relative to c2. In solution, only the more polar c1 conformer has been detected, due to its stronger solvation energy relative to that of the c2 conformer. The mean carbonyl frequency shifts (Δν) close to zero, in CCl4, for the single νCO band of the title compounds 1–7 gives further support for its assignment to the c1 conformer as both the quasi-cis conformer of the α-ethylsulfonylacetophenones and the gauche conformer of the α-bromocetophenones present (Δν) values close to zero. X-ray diffraction analysis for 3 indicates that it exists in the solid state in the c′1 conformation, which is reasonably close to the c1 one, and it is stabilised intramolecularly by the same interactions responsible for the stabilisation of conformer c1 in the gas phase. Furthermore, these molecules form centro-symmetric dimers in the crystal, which are stabilised through two pairs of intermolecular hydrogen bonds, i.e. H[o-Ph]δ+⋯OSO2δ− and H[α-CH]δ+⋯OSO2δ−.

An efficient synthesis of 2'- and 3'-substituted diethyl 1-methylthio-2-oxo-2-phenylethylphosphonates 3a-k from 2'- and 3'-substituted benzoyl chlorides 2a-k using diethyl methylthio-1-lithiomethylphosphonate is described.

The analysis of infrared (IR) carbonyl bands of some 4′-substituted 2-(phenylselanyl)-2-(ethylsulfonyl)-acetophenones 1 – 5 bearing substituents NO 2 1 , Br 2 , H 3 , Me 4 and OMe 5 , supported by B3LYP/6–31 + G(d,p) and single point polarizable continuum model calculations, along with natural bond orbital (NBO) analysis (for 1 , 3 , 5 ) and X-ray diffraction (for 4 ) was performed. Theoretical data indicated the existence of two stable conformations: c 1 and c 2 . The former exhibits the highest ν CO frequency and corresponds to the most stable (for 1 – 5 ) and to the most polar one (for 2 – 4 ). The sum of the energy contributions of selected orbital interactions (NBO analysis) of 1 , 3 and 5 is quite similar for both conformers. Nevertheless, adding the LP O(CO) → σ ∗ C H[CH2(Et)] and LP O(SO2) → σ ∗ C H( o SePh) orbital interaction energies, the c 1 conformer becomes significantly more stable than the c 2 one. The occurrence of these hydrogen bonds plays an important role in determining the geometry of the c 1 conformer. This geometry allows the oppositely charged O δ− (CO) ⋯S δ+ (SO2) and O δ− (SO2) ⋯C δ+ (CO) atoms of the carbonyl and sulfonyl groups to assume interatomic distances shorter than the sum of the van der Waals radii that stabilize the referred conformer. Likewise, this geometry favours the O δ− (CO) ⋯O δ− (SO2) short contact and the consequent repulsive field effect that increases the ν CO frequency of the c 1 conformer to a greater extent with respect to that of the c 2 one. Therefore, the more intense higher frequency carbonyl doublet component in the IR spectrum in solution can be ascribed to the c 1 conformer and the less intense component at lower frequency to the c 2 one. X-ray single crystal analysis of 4 indicates that this compound adopts the c 1 geometry. The molecules in the solid are linked in centrosymmetrical pairs through C9 H10⋯O36 hydrogen bond interaction along with the LP Se ⋯π Ph interaction.

The νCO IR analysis of the 2-fluoro-substituted N,N-dimethylacetamides RC(O)NMe2 [RFCH2 (1), F2CH (2) and F3C (3)] and of the parent N,N-dimethylacetamide [RCH3 (4)] in solvents of increasing polarity suggests the occurrence of Fermi resonance for 2, 3 and 4 and of cis–gauche rotational isomerism for 1. The 1st overtone analysis along with ab initio calculations at MP2/6−31+G(d,p) level are in agreement with the existence of the cis and gauche conformers for 1 and indicate the occurrence of cis–gauche and gauche–gauche conformers for 2 and of a single cis–gauche–gauche rotamer for 3. The stabilisation of the gauche rotamer with respect to the cis rotamer for 1 and of the gauche–gauche rotamer over the cis–gauche rotamer for 2, along with the unique cis–gauche–gauche rotamer for 3 is discussed in terms of a −I inductive effect of the CFn group, a Repulsive Field Effect between the CO and C−F dipoles and the orbital interaction between one or two fluorine 2p lone pairs (in the gauche conformation) and the π CO ∗ orbital. Eigenvector analysis shows that the fluorine 2p orbital coefficient at the LUMO increases progressively, going from the cis–gauche–gauche rotamer of 3 to the cis–gauche rotamer of 2, to the gauche–gauche rotamer of 2 and to the gauche rotamer of 1. Carbonyl frequency gauche shifts (Δν) are in line with this trend and support the π CO ∗ / n F orbital increases in the same direction.

X-ray diffraction analyses of 2-substituted cyclohexanone oximes C5H9(X)C=NOH [X = SMe (1), NMe2 (2)] and of the parent compound [X = H (3)] showed that their cyclohexyl rings are in a slightly distorted chair conformation. These compounds assume in the solid state the (E) configuration bearing the 2-substituents in the axial conformation. Compounds (1) and (2) exist as dimeric and polymeric hydrogen-bond associates, respectively. Low-temperature X-ray analysis of the cyclohexanone oxime (3) showed that the molecules are associated forming two independent trimers. The dimer in (1) and the trimer in (3) are built up via [O—H...N=C] hydrogen bonds, while the polymer of (2) is via the [OH...NMe2] hydrogen bond. The comparative IR νOH and νC=N analysis of the title compounds, in the solid state and in CCl4 solution, fully supports the nature of the associates for (1)–(3) obtained by X-ray diffraction. The IR azomethyne frequency shift analysis (ΔνC=N) also suggests the occurrence of the πC=N/σ*C—X orbital interaction which stabilizes the axial conformations of (1) and (2).

Information on the geometric and electronic structures of α-diethoxyphosphoryl carbonyl derivatives, (RO) 2 P(O)CH 2 C(O)X, ( 1 – 5 , X=CH 3 1 , CH 3 CH 2 O 2 , CH 3 CH 2 S 3 , C 6 H 5 4 , (CH 3 CH 2 ) 2 N 5 ), is obtained by UV photoelectron spectroscopy and ab initio calculations. At the HF level, the CH 2 –P bond is gauche to the carbonyl group except in 5 . However, at the DFT and MP2 levels, the gauche conformation prevails for all the derivatives, in agreement with the spectroscopic data. This conformation is dictated by the interplay of the electronic interactions between the XC(O) and (RO) 2 P(O) groups with two short contacts between pairs of oppositely charged atoms. The negatively charged carbonyl oxygen and one of the oxygen atoms bonded to phosphorus lie at distances shorter than (or close to) the sum of the corresponding van der Waals radii from the positively charged phosphorus and carbonyl carbon atom, respectively. The presence of through-space interactions in the ground and ionised states is confirmed by eigenvector analysis and by the shifts in the MO energies with respect to those of reference compounds. In the ground state the non-bonded interactions are weaker than the corresponding interactions in β-carbonyl sulphones, RSO 2 CH 2 C(O)X, because of the less suitable geometry of the PO 3 group, with respect to the SO 2 R group, for interaction with the β-carbonyl group. In the ionised state, however, the negative charge on the oxygens of the phosphoryl group has a greater capacity to relax toward the ionised XC(O) group thus reducing the ionisation energy values.

Comparative νCO IR analysis of β-carbonylphosphonates [XC(O)CH2P(O)(OR)2: X = Me 1, Ph 2, OEt 3, NEt24 and SEt 5; R = Et] (series I) and β-carbonylsulfones [XC(O)CH2SO2R: X = Me 6, Ph 7, OEt 8, NEt29 and SEt 10; R = Et] (series II) along with ab initio 6-31G** calculations on 1a and 6a (R = Me) suggest the existence of only a single gauche conformer for series I. The negative carbonyl frequency shifts for both series follow approximately the electron-affinities of the π*CO orbital of the parent compounds MeC(O)X 11–15. The less positive asymmetric sulfonyl frequency shifts (ΔνSO2) for II in relation to the phosphoryl frequency shifts (ΔνPO) for I and the larger negative carbonyl frequency shifts for II with respect to the corresponding values for I are in line with the upfield 13C NMR chemical shifts of the carbonyl carbon for II compared to I. These trends agree with the shorter O(SO2)⋯C(CO) contact in comparison with the O(PO)⋯C(CO) one and are discussed in terms of Olp→π*CO charge transfer and electrostatic interactions, which are stronger for series II than for I, indicating that the sulfonyl oxygen atom is a better electron donor than the phosphoryl oxygen atom. Intrinsic geometrical parameters of OS–CH2 and OP–CH2 moieties seem to be responsible for this behaviour as indicated by X-ray study and ab initio calculations of dialkyl (methylsulfonyl)methylphosphonate MeSO2CH2P(O)(OR)2 (R = Et 18, Me 18a).

Axial equatorial populations were determined for (E)-2-X-cyclohexanone oximes and O-methyl oxime ethers in chloroform by the Eliel method [X = F, Cl, Br, OCH3, N(CH3)2, SCH3]. A novel approach is presented, which uses 1H NMR data from the protons bonded to C-6. The conformational proportions were also obtained from the C-4 chemical shifts, the Z-isomer spectral parameters being taken as reference for calculation. For both series, all substituents adopt preferentially the axial conformation (86– 96%), but the O-methyl oxime ethers present an enhanced axial population compared with the corresponding oximes, owing to the accepted occurrence of a πC = NOH/σ*CX stabilizing interaction. Copyright © 2000 John Wiley & Sons, Ltd.