Intra‐ and Intermolecular H‐Bonds of Alcohols in DMSO, 1H‐NMR Analysis of Inter‐Residue H‐Bonds in Selected Oligosaccharides: Cellobiose,Lactose, N,N′‐Diacetylchitobiose,Maltose, Sucrose,Agarose, and Hyaluronates

Inter‐residue H‐bonds of oligosaccharides in (D₆)DMSO have been assigned on the basis of a combined interpretation of the chemical shift (δ(OH)), coupling constant (J(H,OH)), and temperature dependence (Δδ(OH)/ΔT) of OH signals. Cellobiose, lactose, and N,N′‐diacetylchitobiose possess a completely persistent C(3)OH⋅⋅⋅OC(5′) H‐bond. Maltose is characterised by flip‐flop H‐bonds between HO−C(3) and HO−C(2′), and agarose by two weakly persistent inter‐residue H‐bonds. Sucrose forms an equilibrium of differently H‐bonded species, and hyaluronates possess four strong inter‐residue H‐bonds.     

Hydrogen Bonding of Fluorinated Saccharides in Solution: F Acting as H‐Bond Acceptor in a Bifurcated H‐Bond of 4‐Fluorinated Levoglucosans

4‐Fluorinated levoglucosans were synthesised to test if OH???F H‐bonds are feasible even when the O???F distance is increased. The fluorinated 1,6‐anhydro‐β‐D ‐glucopyranoses were synthesised from 1,6 : 3,4‐dianhydro‐β‐D ‐galactopyranose ( 8 ). Treatment of 8 with KHF₂ and KF gave 43% of 4‐deoxy‐4‐fluorolevoglucosan ( 9 ), which was transformed into the 3‐O‐protected derivatives 13 by silylation and 15 by silylation, acetylation, and desilylation. 4‐Deoxy‐4‐methyllevoglucosan ( 19 ) and 4‐deoxylevoglucosan ( 21 ) were prepared as reference compounds that can only form a bivalent H‐bond from HO? C(2) to O? C(5). They were synthesised from the ⁱPr₃Si‐protected derivative of 8 . Intramolecular bifurcated H‐bonds from HO? C(2) to F? C(4) and O? C(5) of the 4‐fluorinated levoglucosans in CDCl₃ solution are evidenced by the ¹H‐NMR scalar couplings ^h1J(F,OH) and ³J(H,OH). The OH???F H‐bond over an O???F distance of ca. 3.0 Å is thus formed in apolar solvents, at least when favoured by the simultaneous formation of an OH???O H‐bond.     

Oligonucleosides with a Nucleobase‐Including Backbone,Part 7

The conformational analysis of 7 was carried out in (D₆)DMSO and in mixtures of (D₆)DMSO and CDCl₃ to evaluate the syn/anti conformations, relevant to the pairing propensity of this type of nucleotide analogue. The HO−C(5′) of unit I and of unit II of the dimer 7 form an intramolecular H‐bond to N(3). In (D₆)DMSO, the C(5′)−OH⋅⋅⋅N(3) H‐bond in unit I is partially broken, while that in unit II persists to a larger extent. The syn conformation prevails for unit I and particularly for unit II. The furanosyl moieties adopt predominantly a 2′‐endo conformation that is largely independent of the solvent.     

Influence of an Ethynyl or a Buta‐1,3‐diynyl Group on the Chemical Shifts of Hydroxy Groups of Glucopyranoses

A comparison of the OH chemical shifts for 1‐mono‐, 4‐mono‐, and 1,4‐diethynylated and 1,4‐buta‐1,3‐diynylated glucopyranoses with those of β‐D ‐glucopyranose ( 1 ) identified characteristic increments for the OH (downfield) shifts of the alkynylated glucopyranoses in (D₆)DMSO solution. For ethynylated derivatives, the increments vary from 0.05 ppm for HO C(6) (replacement of HO C(1) by an axial ethynyl group) to 0.5 ppm for HO C(2) (replacement of HO C(1) by an equatorial ethynyl group). The increments for buta‐1,3‐diynylated derivatives are larger, and vary from 0.1 to 0.7 ppm. The influence on the shift for vicinal OH groups is stronger for such a substitution at C(1) rather than at C(4).     

A Comparison of Glucose‐ and Glucosamine‐Related Inhibitors: Probing the Interaction of the 2‐Hydroxy Group with Retaining β‐Glucosidases

The inhibition of the β‐glucosidases from sweet almonds and Caldocellum saccharolyticum at varying pH values by the glucosamine‐related inhibitors 1 – 7 has been compared to the inhibition by the known glucose analogues 8 – 14 . The amino derivatives 3 , 4 , 6 , and 7 were prepared in one step from the known 15 – 18 (Scheme 1), and the amino‐1,2,3‐triazole 5 by a variant of the synthesis leading to the glucose analogue 12 (Scheme 2). The key step for the preparation of the aminoimidazole 1 and of the amino‐1,2,4‐triazole 2 is the regioselective cleavage of the benzyloxy group at C(2) of the gluconolactam 35 and the mannonolactam 57 , respectively, by BCl₃ and Bu₄NBr (Schemes 3 and 4, resp.). The pH optimum for the inhibition by the amines is lower than their pK_HA values, evidencing that they are bound as ammonium salts and that H‐bonding between C(2)−NH and the cat. base B⁻ contributes more strongly to binding than any possible H‐bond to the NH₂−C(2) group. The influence of the ammonium group on the inhibitory strength correlates with the basicity of the `glycosidic heteroatom'. The strongest increase of the inhibitory strength is observed for the amines lacking a `glycosidic heteroatom' (ΔΔG(OH→NH)=−1.5 to −2.9 kcal/mol). The increase is less pronounced for the amino derivatives 3 – 4 , which possess a weakly basic `glycosidic heteroatom' (ΔΔG(OH→NH)=−0.6 to −1.1 kcal/mol); the amino compounds 1 and 2 , which possess a strongly basic `glycosidic heteroatom', are weaker inhibitors than the corresponding hydroxy compounds, as expressed by ΔΔG(OH→NH) between +4.3 and +4.7 kcal/mol for the amino‐imidazole 1 , and between +2.3 and 2.8 kcal/mol for the amino‐1,2,4‐triazole 2 , denoting the dominant detrimental influence of a C(2)−NH group on the H‐bond acceptor properties of a sufficiently basic `glycosidic heteroatom'.     

An Experimental Evidence of a Metal−Metal Bond in μ‐Carbonylhexacarbonyl[μ‐(5‐oxofuran‐2(5H)‐ylidene‐κC,κC)]‐dicobalt(Co−Co)[Co2(CO)6(μ‐CO)(μ‐C4O2H2)]

The orthorhombic crystal structure of [Co₂(CO)₆(μ‐CO)(μ‐C₄O₂H₂)] ( 1 ) was determined at 150 K (Fig. 1). Two C−H⋅⋅⋅O bonds connect the molecules, forming waving ribbons along the b axis. The experimental electron density, determined with the aspherical‐atom formalism, was analyzed with the topological theory of molecular structure. The presence of the Co−Co bond critical point indicates for the first time the existence of a metal−metal bond in a system with bridged ligands. The bond critical properties of the intramolecular bonds and of the intermolecular interactions show features similar to those found in [Mn₂(CO)₁₀], confirming our previously established bonding classification for organometallic and coordination compounds.     

Hydrogen‐Bonding in Cyclic 2‐(3‐Oxo‐3‐phenylpropyl)‐Substituted 1,3‐Diketones: 17O‐NMR Spectra and X‐Ray Structure Determination

Structures of cyclic 2‐(3‐oxo‐3‐phenylpropyl)‐substituted 1,3‐diketones 4a – c were determined by ¹⁷O‐NMR spectroscopy and X‐ray crystallography. In CDCl₃ solution, compounds 4a – c form an eight‐membered‐ring with intramolecular H‐bonding between the enolic OH and the carbonyl O(11)‐atom of the phenylpropyl group, as demonstrated by increased shielding of specifically labeled 4a – c in the ¹⁷O‐NMR spectra (Δδ(¹⁷O(11))=36 ppm). In solid state, intermolecular H‐bonding was observed instead of intramolecular H‐bonding, as evidenced by the X‐ray crystal‐structure analysis of compound 4b . Crystals of compound 4b at 293 K are monoclinic with a=11.7927 (12) Å, b=13.6230 (14) Å, c=9.8900 (10) Å, β=107.192 (2)°, and the space group is P2₁/c with Z=4 (refinement to R=0.0557 on 2154 independent reflections).     

Kinetic Study and NBO Analysis of the Dehydrogenation Mechanism of Five‐membered Ring Heterocyclic 2,5‐Dihydro‐[furan,thiophene, selenophene

The theoretical study of the dehydrogenation of 2,5‐dihydro‐[furan ( 1 ), thiophene ( 2 ), and selenophene ( 3 )] was carried out using ab initio molecular orbital (MO) and density functional theory (DFT) methods at the B3LYP/6‐311G**//B3LYP/6‐311G** and MP2/6‐311G**//B3LYP/6‐311G** levels of theory. Among the used methods in this study, the obtained results show that B3LYP/6‐311G** method is in good agreement with the available experimental values. Based on the optimized ground state geometries using B3LYP/6‐311G** method, the natural bond orbital (NBO) analysis of donor‐acceptor (bond‐antibond) interactions revealed that the stabilization energies associated with the electronic delocalization from non‐bonding lone‐pair orbitals [LP(e)_X3] to δ*_{C(1)  H(2)} antibonding orbital, decrease from compounds 1 to 3 . The LP(e)_X3→δ*_{C(1)  H(2)} resonance energies for compounds 1 – 3 are 23.37, 16.05 and 12.46 kJ/mol, respectively. Also, the LP(e)_X3→δ*_{C(1)  H(2)} delocalizations could fairly explain the decrease of occupancies of LP(e)_X3 non‐bonding orbitals in ring of compounds 1 – 3 ( 3 > 2 > 1 ). The electronic delocalization from LP(e)_X3 non‐bonding orbitals to δ*_{C(1)  H(2)} antibonding orbital increases the ground state structure stability, Therefore, the decrease of LP(e)_X3→δ*_{C(1)  H(2)} delocalizations could fairly explain the kinetic of the dehydrogenation reactions of compounds 1 – 3 (k ₁ >k ₂ >k ₃ ). Also, the donor‐acceptor interactions, as obtained from NBO analysis, revealed that the (_C(4)C(7)→δ*_{C(1)  H(2)} resonance energies decrease from compounds 1 to 3 . Further, the results showed that the energy gaps between (_C(4)C(7) bonding and δ*_{C(1)  H(2)} antibonding orbitals decrease from compounds 1 to 3 . The results suggest also that in compounds 1 – 3 , the hydrogen eliminations are controlled by LP(e)→δ* resonance energies. Analysis of bond order, natural bond orbital charges, bond indexes, synchronicity parameters, and IRC calculations indicate that these reactions are occurring through a concerted and synchronous six‐membered cyclic transition state type of mechanism.     

Bestimmung der Struktur von Phenyläthinyllithium in Lösung mittels Tieftemperatur-NMR-Spektroskopie

The dimeric and tetrametic structures of complexes of phenylethinyllithium, as recently discovered by X-ray analysis in the solid state, were also found to be present in solution. Tetrahydrofuran solutions of 1-(⁶Li)-[1-¹³C]-2-phenylethyne in the presence or absence of N,N,N′,N′-tetramethylpolymethylenediamines show a pentuplett ¹³C-NMR signal [δ=140 ppm, J(C,Li)=8.2 Hz] from the labelled C-atom at low temperatures (?95 to ?110°). This proves the dimeric structure. When (⁶Li)BuLi is added, a mixed dimer [(C₆H₅C?CLi)(C₄H₉Li)] is formed [δ=142 ppm, J(C,Li) = 7.8 Hz]. This is converted to a mixed tetramer [(C₆H₅C?CLi)(C₄H₉Li)₃] upon addition of larger amounts of (⁶Li)BuLi, as concluded from a signal at δ = 133.5 ppm, J(C,Li) = 5.6 Hz. The multiplicity of this signal suggests that a static tetramer is present, in which the C-atoms couple only with three next Li-neighbors.     

F···HO intramolecular hydrogen bond as the main transmission mechanism for 1hJF,H(O) coupling constant in 2′‐fluoroflavonol

Flavonoids are useful compounds in medicinal chemistry and exhibit conformational isomerism, which is ruled by intramolecular interactions. One of the main intramolecular forces governing the stability of conformations is the hydrogen bond. Hydrogen bond involving fluorine covalently bonded to carbon has been found to be rare, but it appears in 2′‐fluoroflavonol, although the F···HO hydrogen bond cannot be considered the main effect governing the conformational stability of this compound. Because ¹⁹F is magnetically active and suitable for NMR studies, the ^1hJ_F,H(O) coupling constant can be used as a probe for such an interaction in 2′‐fluoroflavonol. In fact, the ^1hJ_F,H(O) coupling was computationally analyzed in this work, and the F···HO hydrogen bond was found to be its main transmission mechanism, which modulates this coupling in 2′‐fluoroflavonol, rather than overlap of proximate electronic clouds, such as in 2‐fluorophenol. Copyright © 2012 John Wiley & Sons, Ltd.     

GIAO,DFT, AIM and NBO analysis of the N?H···O intramolecular hydrogen‐bond influence on the 1J(N,H) coupling constant in push–pull diaminoenones

In the series of diaminoenones, large high‐frequency shifts of the ¹H NMR of the N? H group in the cis‐position relative to the carbonyl group suggests strong N? H···O intramolecular hydrogen bonding comprising a six‐membered chelate ring. The N? H···O hydrogen bond causes an increase of the ¹J(N,H) coupling constant by 2–4 Hz and high‐frequency shift of the ¹⁵N signal by 9–10 ppm despite of the lengthening of the relevant N? H bond. These experimental trends are substantiated by gauge‐independent atomic orbital and density functional theory calculations of the shielding and coupling constants in the 3,3‐bis(isopropylamino)‐1‐(aryl)prop‐2‐en‐1‐one (12) for conformations with the Z‐ and E‐orientations of the carbonyl group relative to the N? H group. The effects of the N? H···O hydrogen‐bond on the NMR parameters are analyzed with the atoms‐in‐molecules (AIM) and natural bond orbital (NBO) methods. The AIM method indicates a weakening of the N? H···O hydrogen bond as compared with that of 1,1‐di(pyrrol‐2‐yl)‐2‐formylethene (13) where N? H···O hydrogen bridge establishes a seven‐membered chelate ring, and the corresponding ¹J(N,H) coupling constant decreases. The NBO method reveals that the LP(O) →σ*_{N? H} hyperconjugative interaction is weakened on going from the six‐membered chelate ring to the seven‐membered one due to a more bent hydrogen bond in the former case. A dominating effect of the N? H bond rehybridization, owing to an electrostatic term in the hydrogen bonding, seems to provide an increase of the ¹J(N,H) value as a consequence of the N? H···O hydrogen bonding in the studied diaminoenones. Copyright © 2010 John Wiley & Sons, Ltd.     

Experimental Study of Hydrogen Bonding Potentially Stabilizing the 5′‐Deoxyadenosyl Radical from Coenzyme B12

Coenzyme B₁₂ can assist radical enzymes that accomplish the vicinal interchange of a hydrogen atom with a functional group. It has been proposed that the Co? C bond homolysis of coenzyme B₁₂ to cob(II)alamin and the 5′‐deoxyadenosyl radical is aided by hydrogen bonding of the corrin C19? H to the 3′‐O of the ribose moiety of the incipient 5′‐deoxyadenosyl radical, which is stabilized by 30 kJ mol^?1 (B. Durbeej et al., Chem. Eur. J. 2009 , 15, 8578–8585). The diastereoisomers (R)‐ and (S)‐2,3‐dihydroxypropylcobalamin were used as models for coenzyme B₁₂. A downfield shift of the NMR signal for the C19? H proton was observed for the (R)‐isomer (δ=4.45 versus 4.01 ppm for the (S)‐isomer) and can be ascribed to an intramolecular hydrogen bond between the C19? H and the oxygen of CHOH. Crystal structures of (R)‐ and (S)‐2,3‐dihydroxypropylcobalamin showed C19? H???O distances of 3.214(7) Å (R‐isomer) and 3.281(11) Å (S‐isomer), which suggest weak hydrogen‐bond interactions (?ΔG<6 kJ mol^?1) between the CHOH of the dihydroxypropyl ligand and the C19? H. Exchange of the C19? H, which is dependent on the cobalt redox state, was investigated with cob(I)alamin, cob(II)alamin, and cob(III)alamin by using NMR spectroscopy to monitor the uptake of deuterium from deuterated water in the pH range 3–11. No exchange was found for any of the cobalt oxidation states. 3′,5′‐Dideoxyadenosylcobalamin, but not the 2′,5′‐isomer, was found to act as a coenzyme for glutamate mutase, with a 15‐fold lower k_cat/K_M than 5′‐deoxyadenosylcobalamin. This indicates that stabilization of the 5′‐deoxyadenosyl radical by a hydrogen bond that involves the C19? H and the 3′‐OH group of the cofactor is, at most, 7 kJ mol^?1 (?ΔG). Examination of the crystal structure of glutamate mutase revealed additional stabilizing factors: hydrogen bonds between both the 2′‐OH and 3′‐OH groups and glutamate 330. The actual strength of a hydrogen bond between the C19? H and the 3′‐O of the ribose moiety of the 5′‐deoxyadenosyl group is concluded not to exceed 6 kJ mol^?1 (?ΔG).     

Experimental and theoretical study of the intramolecular C–H···N and C–H···S hydrogen bonding effects in the 1H and 13C NMR spectra of the 2‐(alkylsulfanyl)‐5‐amino‐1‐vinylpyrroles: a particular state of amine nitrogen

In the ¹H NMR spectra of the 1‐vinylpyrroles with amino‐ and alkylsulfanyl groups in 5 and 2 positions, an extraordinarily large difference between resonance positions of the H_A and H_B terminal methylene protons of the vinyl group is discovered. Also, the one‐bond ¹J(C_β,H_B) coupling constant is surprisingly greater than the ¹J(C_β,H_A) coupling constant in pyrroles under investigation, while in all known cases, there was a reverse relationship between these coupling constants. These spectral anomalies are substantiated by quantum chemical calculations. The calculations show that the amine nitrogen lone pair is removed from the conjugation with the π‐system of the pyrrole ring so that it is directed toward the H_B hydrogen. These factors are favorable to the emergence of the intramolecular C–H_B???N hydrogen bonding in the s‐cis(N) conformation. On the other hand, the spatial proximity of the sulfur to the H_B hydrogen provides an opportunity of the intramolecular C–H_B???S hydrogen bonding in the s‐cis(S) conformation. Presence of the hydrogen bond critical points as well as ring critical point for corresponding chelate ring revealed by a quantum theory of atoms in molecules (QTAIM) approach confirms the existence of the weak intramolecular C–H???N and C–H???S hydrogen bonding. Therefore, an unusual high‐frequency shift of the H_B signal and the increase in the ¹J(C_β,H_B) coupling constant can be explained by the effects of hydrogen bonding. Copyright © 2013 John Wiley & Sons, Ltd.     

Non‐empirical calculations of NMR indirect carbon–carbon coupling constants. Part 4: Bicycloalkanes

A systematic study of the one‐bond and long‐range J(C,C), J(C,H) and J(H,H) in the series of nine bicycloalkanes was performed at the SOPPA level with special emphasis on the coupling transmission mechanisms at bridgeheads. Many unknown couplings were predicted with high reliability. Further refinement of SOPPA computational scheme adjusted for better performance was carried out using bicyclo[1.1.1]pentane as a benchmark to investigate the influence of geometry, basis set and electronic correlation. The calculations performed demonstrated that classical ab initio SOPPA applied with the locally dense Dunning's sets augmented with inner core s‐functions used for coupled carbons and Sauer's sets augmented with tight s‐functions used for coupled hydrogens performs perfectly well in reproducing experimental values of different types of coupling constants (the estimated reliability is ca 1–2 Hz) in relatively large organic molecules of up to 11 carbon atoms. Additive coupling increments were derived for J(C,C), J(C,H) and J(H,H) based on the calculated values of coupling constants within SOPPA in the model bicycloalkanes, in reasonably good agreement with the known values obtained earlier on pure empirical grounds. Most of the bridgehead couplings in all but one bicycloalkane appeared to be essentially additive within ca 2–3 Hz while bicyclo[1.1.1]pentane demonstrated dramatic non‐additivity of ?14.5 Hz for J(C,C), +16.6 Hz for J(H,H) and ?5.5 Hz for J(C,H), in line with previous findings. Non‐additivity effects in the latter compound established at the SOPPA level should be attributed to the through‐space non‐bonded interactions at bridgeheads due to the essential overlapping of the bridgehead rear lobes which provides an additional and effective non‐bonding coupling path for the bridgehead carbons and their protons in the bicyclopentane framework. Copyright © 2003 John Wiley & Sons, Ltd.     

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.     

The 13C,H coupling constants in structural and conformational analysis: II The correlation of 3J(HCCH) and 3J(CH3CCH) in ethylenes and their methyl derivatives

The vicinal ³J(C H₃C?CH ) coupling constants were determined for a number of propylene derivatives and compared with the ³J(H C?CH ) couplings of the corresponding ethylenes. A linear regression analysis yielded the correlation ³J(CH) = 0.46 ׳ J(HH)+1.58 Hz, the correlation coefficient being 0.956.     

Structural studies on aryl‐substituted enaminoketones and their thio analogues. Part II. Experimental and DFT calculated carbon–carbon coupling constants,nJ(CC)'s (n = 1–3)

Spin–spin carbon–carbon coupling constants across one, two and three bonds, J(CC), have been measured for a series of aryl‐substituted Z‐s‐Z‐s‐E enaminoketones and their thio analogues. As a result, a large set, altogether 178, of J(CC)s has been obtained. It consists of 82 couplings across one bond, 31 couplings across two bonds and 65 couplings across three bonds. Independently, the DFT calculations at the B3PW91/6‐311++G(d,p)//B3PW91/6‐311++G(d,p) level yielded a set of theoretical J(CC) values. A comparison of these two sets of data gave an excellent linear correlation with parameters a and b close to ideal; a = 0.9978 which is not far from unity and b = 0.22 Hz which is close to zero. The ¹J(CC) couplings determined for the crucial fragment of the molecules, i.e. ? C?C? C?O (or ? C?C? C?S), are: ¹J(C?C) ≈ 68 Hz (67 Hz) and ¹J(C? C) = 60.5 Hz (60.0 Hz). The corresponding couplings found for the Z‐s‐Z‐s‐E isomer of the parent enaminoketone, 4‐methylamino‐but‐3‐en‐2‐one are 64.1 and 59.3 Hz, respectively. The most sensitive towards substitution of the oxygen atom by sulfur are two‐bond couplings between the α‐vinylic and aromatic C_ipso carbon atoms, which attain 12 Hz in the enaminoketone derivatives and decrease to 5 Hz in their thio analogues. Copyright © 2009 John Wiley & Sons, Ltd.     

Configurational assignment in alkyl‐branched sugars via the geminal C,H coupling constants

The measurement of the magnitude and sign of ²J(C,H) couplings offers a reliable way to determine the absolute configuration at a carbon center in a fixed cyclic system. A decrease of the dihedral angle ? in the O—C_A—C_B—H fragment always leads to a change of the ²J(C_A,H_B) coupling to more negative values, independent of the type and position of substituents at the two carbon centers. The orientations of the two substituents at C‐3 of the epimeric pair 1 and 2 were determined unambiguously through the measurement of the geminal coupling constants between C‐3 and the hydrogen atoms at C‐2 and C‐4. In particular, ²J(C‐3,H‐2ax) with ?1.5 Hz, ? = 174° in 1 and ?6.6 Hz, ? = 47° in 2 , and ²J(C‐3,H‐4) with +1.5 Hz, ? = 175° in 1 and ?4.7 Hz, ? = 49° in 2 showed the greatest differences between the two epimers. Both couplings therefore allow the determination of the absolute configuration at C‐3. It should be noted, however, that the size of the coupling constants can be different for dihedral angles of nearly identical size, when there are different numbers of electronegative substituents on the two coupling pathways, i.e. no O‐substituent at C‐2, but one axial O‐substituent at C‐4. It becomes clear that it is not sufficient to measure the magnitude of ²J coupling constants only, but that the sign of the geminal coupling is needed to identify the absolute configuration at a chiral center. The coupling of C‐3 with H‐2eq is not useful for the determination of the configuration at C‐3, as the similarity of the dihedral angles ? (O—C‐3—C‐2—H‐2eq) (57° in 1 and 70° in 2 ) leads to identical coupling constants (?6.1 Hz) for both epimers. Copyright © 2003 John Wiley & Sons, Ltd.     

C?H···N and C?H···O intramolecular hydrogen bonding effects in the 1H, 13C and 15 N NMR spectra of the configurational isomers of 1‐vinylpyrrole‐2‐carbaldehyde oxime substantiated by DFT calculations

According to the ¹H, ¹³C and ¹⁵N NMR spectroscopic data and DFT calculations, the E‐isomer of 1‐vinylpyrrole‐2‐carbaldehyde adopts preferable conformation with the anti‐orientation of the vinyl group relative to the carbaldehyde oxime group and with the syn‐arrangement of the carbaldehyde oxime group with reference to the pyrrole ring. This conformation is stabilized by the C? H···N intramolecular hydrogen bond between the α‐hydrogen of the vinyl group and the oxime group nitrogen, which causes a pronounced high‐frequency shift of the α‐hydrogen signal in ¹H NMR (～0.5 ppm) and an increase in the corresponding one‐bond ¹³C–¹H coupling constant (ca 4 Hz). In the Z‐isomer, the carbaldehyde oxime group turns to the anti‐position with respect to the pyrrole ring. The C? H···O intramolecular hydrogen bond between the H‐3 hydrogen of the pyrrole ring and the oxime group oxygen is realized in this case. Due to such hydrogen bonding, the H‐3 hydrogen resonance is shifted to a higher frequency by about 1 ppm and the one‐bond ¹³C–¹H coupling constant for this proton increases by ～5 Hz. Copyright © 2008 John Wiley & Sons, Ltd.     

4‐Amino‐7‐(2‐de­oxy‐2‐fluoro‐β‐d‐arabinofuranos­yl)‐5‐fluoro‐7H‐pyrrolo[2,3‐d]pyrimidine: a bis‐fluorinated analogue of 2′‐deoxy­tubercidin

The title compound, C₁₁H₁₂F₂N₄O₃, exhibits an anti glycosylic bond conformation, with a torsion angle χ = −117.8 (2)°. The sugar pucker is N‐type (C4′‐exo, between ³T₄ and E₄, with P = 45.3° and τ_m = 41.3°). The conformation around the exocyclic C—C bond is −ap (trans), with a torsion angle γ = −177.46 (15)°. The nucleobases are stacked head‐to‐head. The crystal structure is characterized by a three‐dimensional hydrogen‐bond network involving N—H⋯O, O—H⋯O and O—H⋯N hydrogen bonds.