B3LYP and MP2 calculations of the enthalpies of hydrogen-bonded complexes of methanol with neutral bases and anions: comparison with experimental data

To perfect a method for building a theoretical hydrogen-bond basicity scale, the enthalpy of hydrogen bonding between methanol and thirteen neutral and anionic bases (MeOH, MeNH2, Me2NH, Et2NH, Me3N, Et3N, Br-, CN-, SH-, Cl-, HCOO-, MeO-, F-) was calculated by DFT and ab initio methods. The theoretical results were compared to selected experimental ones. It appears that B3LYP/6-31+G(d,p) calculations are satisfactory for optimizing the geometry of complexes and giving a general order of basicity. However, they are deficient for reproducing the large effect of alkyl groups on the hydrogen-bond basicity of amines. This deficiency is explained by intermolecular perturbation theory calculations, which show that the alkylation of nitrogen dramatically increases the dispersion energy component not taken into account by the B3LYP functional. Of the methods considered, only MP2/aug-cc-pVTZ calculations are capable of reproducing the binding enthalpy within the experimental error for the first-row acceptor atoms N, O, and F, and of accounting for dispersion effects created by alkylation at the hydrogen-bond acceptor site.     

Solid-state molecular organization and solution behavior of methane-1,1-diphosphonic acid derivatives of heterocyclic amines: the role of the topochemical ring modification and the intramolecular hydrogen bonds in monosubstituted piperid-1-ylmethane-1,1-diphosphonic acids

The crystal structures of 3-methylpiperid-1-ylmethane-1,1-diphosphonic (2), 4-methylpiperid-1-ylmethane-1,1-diphosphonic (3), 2-ethylpiperid-1-ylmethane-1,1-diphosphonic (4), and 2-methylpiperid-1-ylmethane-1,1-diphosphonic (5) acids have been determined and are discussed with respect to their molecular organization and crystal-packing preferences. The chair conformation, predominant also in solution, favors equatorial positioning of the bulky substituents of the heterocyclic N and C atoms. The molecular geometry also provides access to intramolecular hydrogen-bond formation between the axial protons located on the nitrogen atoms, as well as the carbon atoms closest to it, and phosphonic/phosphonate oxygen atoms. The molecules preferably arrange in monolayers, observed in all crystals with an exception of 3. The layers are held in place in the third direction through van der Waals interactions. The analysis of two-dimensional hydrogen-bonded networks is concentrated on revealing how the substituent's topology of the molecule affects the solid-state organization in well-defined structures and is aimed at unraveling the consequences and the possible conformational changes by stepwise network disruption upon crystal dissolution in water. The solution NMR studies are focused on revealing the role that the topochemistry of the substituent plays for the stereodynamics in 2-5. It is demonstrated that in contrast to piperid-1-ylmethane-1,1-diphosphonic acid (1), in which the ring inversion/rotation around the C-N bond concerted with the N-H...O hydrogen-bond breaking/formation process leads to a mixture of two interconverting conformers, the concerted N-H...O breaking/rotation/N-H...O formation process in 2 and 3 allows for a predominance of one conformer in solution. However, placement of a substituent at 2-position in the ring hampers the rotation around the C-N bond; this makes 4 and 5 significantly less flexible relative to compounds 1-3. In addition, both compounds 4 and 5 are proved to exist as a mixture of two conformers, the equilibrium of which in acidic solution is shifted towards the conformer found in solid state. In alkaline solutions of 4 and 5, the equilibrium is shifted towards the conformer that is forced by the flipping of the heterocyclic ring. These results correlate well with recently documented differences in the biological potency of this group of compounds.     

Crowded piperidines with intramolecularly hydrogen-bonded nitrogen: synthesis and conformation study

2,2,6,6-Tetramethyl substituted piperidines with a beta-branched N-alkyl substituent were synthesized by the photoreaction of N-Me precursors with ketones. The main conformation features of these sterically-hindered amines (established by NMR and IR spectroscopy) are a ring in the chair form, an eclipsed conformation for the N-substituent and an intramolecular OH...N bond. High barriers for the geminal substituent topomerization were measured for these piperidines at different temperatures by means of line-shape analysis of the temperature-dependent 13C and 1H NMR spectra. An MM3-derived conformation scheme indicated that, for one of the studied analogues, the rotation of the N-substituent determines a slow topomerization rate. A new mechanism of nitrogen inversion--a concerted hydrogen-bond dissociation/nitrogen inversion process--is considered for hydrogen-bonded amines.     

Stereospecific synthesis of C2 symmetric diamines from the mother diamine by resonance-assisted hydrogen-bond directed diaza-Cope rearrangement

Sixteen diphenylethylenediamine analogues including those with electron donating, electron withdrawing, and sterically bulky substituents have been prepared in good overall yields (70-90%) and in enantiomerically pure form (>99% ee) by diaza-Cope rearrangement reaction. A single chiral mother diamine, ((R,R)-1,2-bis-(2-hydroxyphenyl)-1,2-diaminoethane), is reacted with appropriate aldehydes to form the initial diimines that rearrange to give all the product diimines in the (S,S) form. The daughter diamines are obtained by hydrolysis of the product diimines. Density functional theory computation shows that resonance-assisted hydrogen-bond is the main driving force behind all the rearrangement reactions. Chiral high performance liquid chromatography and circular dichroism spectroscopy show that the highly stereospecific rearrangement reactions take place with apparent inversion of stereochemistry.     

Consecutive Intermolecular Reductive Amination/Asymmetric Hydrogenation: Facile Access to Sterically Tunable Chiral Vicinal Diamines and N‐Heterocyclic Carbenes

A highly enantioselective iridium‐ or ruthenium‐catalyzed intermolecular reductive amination/asymmetric hydrogenation relay with 2‐quinoline aldehydes and aromatic amines has been developed. A broad range of sterically tunable chiral N,N′‐diaryl vicinal diamines were obtained in high yields (up to 95 %) with excellent enantioselectivity (up to >99 % ee). The resulting chiral diamines could be readily transformed into sterically hindered chiral N‐heterocyclic carbene (NHC) precursors, which are otherwise difficult to access. The usefulness of this synthetic approach was further demonstrated by the successful application of one of the chiral vicinal diamines and chiral NHC ligands in a transition‐metal‐catalyzed asymmetric Suzuki–Miyaura cross‐coupling reaction and asymmetric ring‐opening cross‐metathesis, respectively.     

Ab Initio Quantum Mechanical Study on the Origin of the pK(a) Differences of the Proton Sponges 1,8-Bis(dimethylamino)naphthalene, 1,8-Bis(dimethylamino)-2,7-dimethoxynaphthalene, 1,6-Dimethyl-1,6-diazacyclodecane, and 1,6-Diazabicyclo[4.4.4]tetradecane

Ab initio quantum mechanical calculations were used in studying the origin of the exceptionally high basicities of four diamines (13-16) with pK(a1) values ranging from 12.1 to 25. The computational approach involved the calculation of the gas-phase proton affinities of the molecules studied at the MP2/6-31G//HF/6-31G level and the solvation energies with the polarizable continuum model at the HF/6-31G level. The calculated gas-phase and aqueous-phase proton affinities of a structurally diverse series of amines were compared with the corresponding experimental gas-phase proton affinities and pK(a1) values. The calculated values were found to be in reasonable agreement with the experimental ones. The high basicities of the studied diamines were found to originate from the nitrogen lone-pair repulsion, solvation effects, and strong intramolecular hydrogen bonds. Each of these factors were found to be able to increase the pK(a1) values of the high-basicity diamines by 2-6 pK(a) units. The relative contributions of the factors varied between the compounds. The nitrogen lone-pair repulsion was estimated to be the most important factor in increasing the pK(a1) values. In addition, barriers for proton transfers between the nitrogens of selected diamines were calculated, and comparison was made between the barrier heights and the geometries of the diamines.     

Synthesis of C2-symmetrical chiral diamines: diastereoselective addition to bis(1,3-oxazolidinyl)alkanes with Grignard reagents

Asymmetric syntheses of C₂-symmetrical chiral 1,4- and 1,5-diamines with stereogenic centers adjacent to the nitrogen atom have been accomplished. Chiral diamines were prepared by diastereoselective alkylations of bisoxazolidine, which was derived from (R)-phenylglycinol. Methyl and phenyl Grignard reagents were employed as alkylating reagents. In addition, tertiary chiral diamines were readily converted to primary diamines in high yield.     

The 3-21G(N*) basis set: An economical polarized basis set for ab initio studies on nitrogen-containing molecules

The 3-21G basis set shares with its older cousin, the 4-31G basis set, a tendency to overestimate valence angles at nitrogen atoms and to underestimate seriously barriers to inversion at such atoms. The 6-31G* basis set generally yields greatly improved results in these respects. It is here shown that, for a variety of molecules, supplementation of the 3-21G basis set at three- or two-coordinate nitrogen atoms with a set of six d-functions having exponent 1.0 leads to optimized geometries and inversion barriers at such nitrogen centers in good agreement with results obtained with the 6-31G* basis set. This supplemented basis set, designated as 3-21G(N*), also leads to calculated vibrational frequencies in good agreement with those calculated with the 6-31G* basis set. The 3-21G(N*) basis set offers an economical alternative to the 6-31G* basis set, particularly for molecules containing several first-row atoms other than nitrogen.     

Highly Enantioselective Direct Synthesis of Endocyclic Vicinal Diamines through Chiral Ru(diamine)‐Catalyzed Hydrogenation of 2,2′‐Bisquinoline Derivatives

An asymmetric hydrogenation of 2,2′‐bisquinoline and bisquinoxaline derivatives, catalyzed by chiral cationic ruthenium diamine complexes, was developed. A broad range of chiral endocyclic vicinal diamines were obtained in high yields with excellent diastereo‐ and enantioselectivity (up to 93:7 dl/meso and >99 % ee). These chiral diamines could be easily transformed into a new class of chiral N‐heterocyclic carbenes (NHCs), which are important but difficult to access.     

Aziridines. V. Etude par rmn de l'inversion de l'azote dans les aziridines symétriques à fonetion amine secondaire

This article describes the nitrogen inversion in two symétrie secondary aziridines. It was possible, by nmr, in avoiding the exchange of NH proton with water, to record spectra at different temperatures and to determine the temperature of coalescence. Persistance of coupling H? C? N? H after coalescence demonstrates the attribution of signals multiplicity to both invertomers.     

Synthesis of new chiral amines with a cyclic 1,2-diacetal skeleton derived from (2R, 3R)-(+)-tartaric acid

The syntheses of new chiral cyclic 1,2-diacetals from (2R, 3R)-( )-tartaric acid are described. C(2)-symmetrical diamines were prepared via direct amidation of the tartrate or from the corresponding bismesylate via reaction with sodium azide. For C1-symmetrical compounds, the Appel reaction was used to form the key intermediate, a monochlorocarbinol, from the diol. Some of the new chiral compounds, produced in good to high yields, may be potentially useful as asymmetric organocatalysts or as nitrogen and sulfur chelating ligands for asymmetric metal catalyzed reactions. Thus, a bis-N-methyl-methanamine derivative, used in substoichiometric amounts, was found to catalyze the enantioselective addition of cyclohexanone to (E)-beta-nitrostyrene with high diastereoselectivity (syn / anti = 92:8), albeit giving moderate optical purity (syn: 30 %).     

Cyclic vinyl p-tolyl sulfilimines as chiral dienophiles: theoretical study on the stereoselectivity, Lewis acid catalysis, and solvent effects in their Diels-Alder reactions

The theoretical study reported in the present work deals with chiral cyclic vinyl sulfilimines and their reactivity as dienophiles in [4 + 2] cycloaddition reactions, using B3LYP/6-31G(d)//AM1 and B3LYP/6-31G(d)//B3LYP/6-31G(d) model chemistries. Consideration of Lewis acid catalysis, illustrated by BF(3), decreases the activation energies of the cycloaddition process while the charge transfer from the diene to the sulfilimine is augmented. The [4 + 2] cycloaddition reactions of sulfilimines with both furan and cyclopentadiene occur in the gas phase with endo stereoselectivity, which is more pronounced with the latter diene. Endo-exo energy differences in the gas phase with the B3LYP/6-31+G(d)//B3LYP/6-31+G(d), B3LYP/6-31G(d)//B3LYP/6-31G(d), and B3LYP/6-31G(d)//AM1 model chemistries are almost the same. Solvent effects are responsible for the inversion of the stereoselectivity in the reactions of sulfilimines with furan because of the great difference in the dipole moments in endo and exo approaches.     

Design of C2-chiral diamines that are computationally predicted to be a million-fold more basic than the original proton sponges

A set of C2-chiral diamines 18-21 based on 1,6-diazacyclodecane have been identified whose conjugate acids are predicted by B3LYP/6-31G calculations to have pKa values of approximately 23-6 on the water scale (pKa = 30-33 in MeCN); they are also expected to be kinetically active, but essentially nonnucleophilic. Strain relief on protonation largely determines the basicity of these compounds, and the key to the design of stronger bases is limiting conformational freedom, especially by preventing nitrogen inversion, through the introduction of additional ring fusions. 15,16-Dimethyl-15,16-diazatricyclo[9.3.1.1(4,8)]hexadecane (20) is examined in detail and shown to exist in 10 diastereomeric forms as a result of in-/out-isomerism. The predicted pKa values for these diastereomers range over 14 log units.     

Medium effects on the decarboxylation of a biotin model in pure and mixed solvents from QM/MM simulations

The decarboxylation of imidazolidin-2-one-1-carboxylate anion 2 has been investigated via combined quantum and statistical mechanics methodology. Monte Carlo statistical mechanics simulations utilizing free-energy perturbation theory and PDDG/PM3 for the QM method yielded free-energy profiles for the reaction in water, methanol, acetonitrile, and mixed solvents. The results for free energies of activation are uniformly in close accord with experimental data and reflect large rate accelerations in progressing from protic to dipolar aprotic media. Structural and energetic analyses confirm that the rate retardation in protic solvents comes from loss of hydrogen bonding in progressing from the carboxylate anion 2 to the more charge-delocalized transition state (TS). The structure of the TS is found to be significantly affected by the reaction medium; it occurs at a 0.2-A shorter C-N separation in protic solvents than in acetonitrile. Characterization of the hydrogen bonding for 2 and the TS also provided insights for design of decarboxylase catalysts, namely, it is desirable to have three hydrogen-bond donating groups positioned to interact with the ureido oxygen along with two hydrogen-bond donors positioned to interact with the ureido nitrogen of the breaking C-N bond.     

Microwave assisted cyclocondensation of dialdehydes with chiral diamines forming calixsalen type macrocycles

Microwave irradiation of various dialdehydes and chiral diamines afforded chiral macrocyclic imines in moderate to good yields. Linked dialdehydes predominantly form [2+2] macrocycles whereas dialdehydes without linkers yield [3+3] macrocycles. This is the first report of template-free synthesis of calixsalen-type macrocycles formed in shorter reaction times under microwave conditions. In all the reactions, the salts of chiral diamines were used in contrast to the free diamines normally employed.     

Coalescence coupled with either coagulation or flocculation in dilute emulsions

In current theories [R.G.P. Borwankar, L.A. Lobo, D.T.G. Wasan, Colloids Surf. 69 (1992) 35; K.D. Danov, N.D. Denkov, D.N. Petsev, R. Borwankar, Langmuir 9 (1993) 1731; S.S. Dukhin, J. Sjöblom, J. Dispers. Sci. Technol. 19 (1998) 311], emulsion destabilization is considered as the combined processes of droplet coagulation/flocculation and coalescence. Irreversible aggregation is usually called coagulation, and the term flocculation is used for reversible aggregation. These theories have different conditions of applicability which are not specified. An approximate criterion for discrimination between coalescence coupled with either coagulation or flocculation in dilute emulsions is proposed. Such discrimination is made possible by comparing the characteristic time for coagulation (Smoluchowski time) with that for floc fragmentation (droplet doublet lifetime, τ_d). As droplet dimension and electrolyte concentration decrease, and the Stern potential increases, τ_d is reduced and flocculation takes place. The quantity τ_d enables one to specify the conditions for the two separate cases. The important role of retarded van der Waals forces, screening length and hydration forces in emulsion coalescence is demonstrated.     

新型手性双核Salen Zn(II)配合物的分子识别研究

采用新型Salen中间体合成了新型SalenZn(II)配合物.用紫外-可见光谱滴定法研究了主体双核SalenZn(II)与咪唑、二胺类等含氮小分子的分子识别行为,测定了它们的缔合常数.对咪唑类客体的缔合常数顺序为K(Im)>K(2?MeIm)>K(EMeIm);对二胺类客体缔合常数顺序为K(DAP)>K(DAE).主体与咪唑类和二胺类客体的配位数分别是2和1.主体与这些客体的识别过程为放热、熵减的焓驱动反应.利用圆二色光谱研究了识别过程的Cotton效应.用分子力学方法研究了主客体体系的最低能量构型,通过量化计算对实验事实做了进一步解释.     

Asymmetric Ring Opening/Cyclization/Retro‐Mannich Reaction of Cyclopropyl Ketones with Aryl 1,2‐Diamines for the Synthesis of Benzimidazole Derivatives

A highly efficient asymmetric ring‐opening/cyclization/retro‐Mannich reaction of cyclopropyl ketones with aryl 1,2‐diamines has been realized using a chiral N,N′‐dioxide/Sc^III catalyst. Benzimidazoles containing chiral side chains were generated under mild reaction conditions in excellent outcomes (up to 99 % yield and 97 % ee). This method also provides efficient access to chiral benzimidazole‐substituted amide and cycloheptene derivatives.     

The nicotinic pharmacophore: thermodynamics of the hydrogen-bonding complexation of nicotine, nornicotine, and models

The thermodynamics of the hydrogen-bonding complexation of the acetylcholine agonists nicotine and nornicotine and of model pyridines, pyrrolidines, and N-methylpyrrolidines has been measured in CCl(4) by FTIR spectrometry toward a reference hydrogen-bond donor, 4-fluorophenol. Various methods are devised for measuring separately the hydrogen-bond acceptor strength of each nitrogen of nicotine and nornicotine: variation of the stoichiometry of complexation; correlations with electrostatic potentials on nitrogens and with substituent constants in the series of 3-substituted pyridines, 2-substituted pyrrolidines, and 2-substituted N-methylpyrrolidines; and linear free energy relationships between 4-fluorophenol and hydrogen fluoride hydrogen-bonded complexes. It is consistently found that nicotine and nornicotine have two active hydrogen-bond acceptor sites, the pyridine and pyrrolidine nitrogens, and that ca. 90% (for nicotine) and 80% (for nornicotine) of the 1:1 hydrogen-bonded complexes are formed to the pyridine nitrogen, although the pyrrolidine nitrogen is the first protonation site of nicotine and nornicotine in water. The low hydrogen-bond basicity of the pyrrolidine nitrogen in nicotine is mainly explained by the inductive electron-withdrawing and steric effects of the 2-(3-pyridyl) substituent. The partition of the Gibbs energy of the isomerism of complexation (AH...Nsp(2) <==> AH...Nsp(3)) into enthalpic and entropic contributions shows that the selectivity in favor of the pyridine nitrogen is driven by entropy. It is important to recognize the bifunctionality of nicotine in hydrogen bonding for understanding its lipophilicity and molecular recognition in non protonic media. When monoprotonated on their sp(3) nitrogen, nicotine and nornicotine keep, through their sp(2) nitrogen, a significant hydrogen-bond basicity which is greater than that of the ester group of acetylcholine.     

Cobalt–Nitrogen‐Doped Helical Carbonaceous Nanotubes as a Class of Efficient Electrocatalysts for the Oxygen Reduction Reaction

The oxygen reduction reaction (ORR) is of significant importance in the development of fuel cells. Now, cobalt–nitrogen‐doped chiral carbonaceous nanotubes (l/d ‐CCNTs‐Co) are presented as efficient electrocatalysts for ORR. The chiral template, N‐stearyl‐l/d ‐glutamic acid, induces the self‐assembly of well‐arranged polypyrrole and the formation of ordered graphene carbon with helical structures at the molecular level after the pyrolysis process. Co was subsequently introduced through the post‐synthesis method. The obtained l/d ‐CCNTs‐Co exhibits superior ORR performance, including long‐term stability and better methanol tolerance compared to achiral Co‐doped carbon materials and commercial Pt/C. DFT calculations demonstrate that the charges on the twisted surface of l/d ‐CCNTs are widely separated; as a result the Co atoms are more exposed on the chiral CCNTs. This work gives us a new understanding of the effects of helical structures in electrocatalysis.