N-methylpiperidine Betaine Research Articles

Experimental Electron Density Distribution in Two Cocrystals of Betaines with p-Hydroxybenzoic Acid

Experimental determination of electron density distribution in crystals by means of high-resolution X-ray diffraction allows, among others, for studying the details of intra- and inter-molecular interactions. In case of co-crystals, this method may help in finding the conditions of creating such species. The results of such analysis for two co-crystals containing betaines, namely trigonelline (TRG: nicotinic acid N-methylbetaine, IUPAC name: 1-methylpyridinium-3-carboxylate) and N-methylpiperidine betaine (MPB: 1-methylpiperidinium-1-yl-carboxylate) with p-hydroxybenzoic acid (HBA) are reported. TRG-HBA crystallizes as a hydrate. For both of the co-crystals, high-quality diffraction data were collected up to sinθ/λ = 1.13 Å−1. Hansen-Coppens multipolar model was then applied for modelling the electron density distribution and Atoms-In-Molecules approach was used for detailed analysis of interactions in crystals. A number of intermolecular interactions was identified, ranging from strong O-H···O hydrogen bonds through C-H···O to C-H···π and π···π interactions. Correlations between the geometrical characteristics of the contacts and the features of their critical points were analyzed in detail. Atomic charges show that in zwitterionic species there are regions of opposite charges, rather than charges that are localized on certain atoms. In case of MPB-HBA, a significant charge transfer between the components of co-crystal (0.5 e) was found, as opposed to TRG-HBA, where all of the components are almost neutral.

Structural, spectroscopic and theoretical studies of the 1:1 complex of N-methylpiperidine betaine with squaric acid

Abstract The 1:1 complex of N-methylpiperidine betaine, MPB, with squaric acid, H2SQ, has been characterized by single-crystal X-ray analysis, FTIR and NMR spectroscopies, and by DFT calculations. The crystals are orthorhombic, space group Pbca. Two non-equivalent O H···O hydrogen bonds of 2.472(1) and 2.508(2) A link H2SQ with MPB. The piperidinium ring has a chair conformation with the methyl group in the equatorial position and the CH2COO− substituent in the axial one. The geometry of the optimized structures of the MPB·H2SQ complex at the B3LYP/6-31G(d,p) level of theory, in a vacuum and solvated by water, have been used to calculate harmonic IR frequencies and to predict the chemical shifts in H2O.

Conformational richness and multiple Z′ in salt co-crystal of N-methylpiperidine betaine with N-methylpiperidine betaine hexafluorosilicate

The co-crystal structure of N-methylpiperidine betaine with N-methylpiperidine betaine hexafluorosilicate represents an unusual case of a salt co-crystal with a high Z' value (3), unexpected conformational variability, and with nearly 50% of its contents disordered. The betaine units from the salt and co-crystal formers are paired into several homoconjugated dimers via very short, linear O(-)...H(+)...O(-) bridges. These hydrogen bonds are the dominating interactions in the co-crystal structure, in variance with the simple hexafluorosilicate salt, which has a structure governed by COOH...F hydrogen bonds. The SiF(2-)(6) anion in the co-crystal structure has only C-H...F interactions with the betaine units. The zwitterion:cation:anion stoichiometry is 3:3:1.5. Some of the betaine units display disorder, but each case is different. One of the SiF(2-)(6) anions is ordered while possessing exact crystallographic symmetry. The other one is disordered in a general position. In addition, there are three water molecules in the crystal structure. One is fully ordered, one has an H atom disordered in two positions and the third one occupies two alternative positions with unequal populations.

Structure of co-crystal of N-methylpiperidine betaine– l(+)-tartaric acid

N-Methylpiperidine betaine (MPB) and l(+)-tartaric acid form a six-molecular non-centrosymmetric crystalline complex through two O H⋯O C and four COO⋯HOOC hydrogen bonds. The structure of this co-crystal has been determined by X-ray diffraction. The molecular structure of the title compound has been studied by FTIR, Raman and NMR spectroscopies and calculations by the B3LYP/3-31G(d,p) level of theory. This co-crystal belongs to the monoclinic system, space group P2 1 with a = 10.2691(4), b = 9.4528(3), c = 24.0637(7) Å, β = 98.227(3)°, Z = 2, R = 0.026. Two molecules of TA and four molecules of MPB form a six-membered, asymmetric, hydrogen-bonded cluster, [(MBP) 2TA] 2. The core of the cluster is formed by two TA molecules linked by O H⋯O C hydrogen bonds of the lengths 2.786(1) and 2.761(1) Å, into a cyclic asymmetric dimer. Four MPB molecules are bonded to the TA core by four COO⋯HOOC hydrogen bonds of the lengths 2.493(1), 2.496(1), 2.511(1) and 2.512(1) Å. The piperidine ring has a chair conformation, however, the CH 2COO − substituent at the nitrogen atom occupies the opposite positions (axial and equatorial) in MPB moieties bonded to each TA. The clusters are bonded into infinite chains, parallel to the y-axis, by the O H⋯O C hydrogen bonds of 3.051(1) Å. In the optimized structure of the title complex the fragments of (MPB) 2TA in the cluster are twisted, which causes a shortening of the intermolecular hydrogen bonds between the TA molecules. The FTIR spectrum is consistent with the X-ray structure.

Structure of complex of N-methylpiperidine betaine with p-hydroxybenzoic acid studied by X-ray, FT-IR and DFT methods

Crystal structure of the complex of N-methylpiperidine betaine ( N-carboxymethyl- N-methylpiperidinium inner salt, MPB) with p-hydroxybenzoic acid (HBA) has been determined by X-ray diffraction. The crystals are triclinic, space group Pī, with a = 6.1156(5), b = 10.6869(10), c = 12.0320(10) Å, α = 109.55(1)°, β = 95.25(1)°, γ = 99.22(1)°, Z = 2, R = 0.034. Two molecules of p-hydroxybenzoic acid and two molecules of N-methylpiperidine betaine are linked together forming a centrosymmetric dimer, (MPB·HBA) 2, by four O–H···O hydrogen bonds of lengths 2.622(1) and 2.617(1) Å, between the carboxylic and hydroxy groups of HBA and both oxygen atoms of the carboxylate group of MPB, respectively. The piperidine ring has a chair conformation with the CH 2COO − substituent in the axial position and the CH 3 group in the equatorial one. Two parallel aromatic rings in (MPB·HBA) 2 are distanced by 3.457 Å. In the crystals the complexes form “islands” related to the neighboring complexes by the inversion centers, weak C–H···O bonds and van der Waals forces. A broad band in the 3100–2400 cm −1 region and two bands attributed to the νC O (1689 cm −1) and ν asCOO (1607 cm −1) vibrations in the FT-IR spectrum confirm the structure of the title complex. The two structures of MPB·HBA, denoted as A and B, have been optimized by the B3LYP/6-31G(d,p) method. In A, MPB forms a O–H···O hydrogen bond (2.562 Å) with the carboxylic group of HBA shorter than in the crystals, while in B it interacts with the phenolic group of HBA by a longer O–H···O hydrogen bond (2.661 Å) than in the crystals. Complex A is slightly more stable than B (0.15 kcal/mol).

B3LYP study of the conformers and rotamers of isostructural N-methylpiperidine betaine hydrochloride and (1-methylcyclohexyl)-acetic acid. The effect of electrostatic attraction on rotation barriers

The structure and rotational barriers of axial and equatorial N-methylpiperidine betaine hydrochlorides, MPBH·Cl, and (1-Methylcyclohexyl)-acetic acid, MCHA, have been carried out at the B3LYP/6-31G(d,p) level of theory. The calculated rotational barrier for the axial and equatorial stereoisomers about the N +–C(8) bond in MPBH·Cl are 8.17 and 8.30 kcal/mol, whereas those for the rotation about the C(1)–C(8) bond in MCHA are 4.11 and 4.91 kcal/mol, respectively. The higher rotation barriers in MPBH·Cl are a result of the electrostatic attractions between the positively charged nitrogen atom with the negatively charged oxygen atoms of the carboxylic group and the chloride anion. Structures of the most stable rotamers of MPBH·Cl and MCHA are analyzed.

The influence of halide anions on the molecular structure of bis( N-methylpiperidine betaine) monocation with short hydrogen bond

The crystal structure of the 2:1 (basic) salt of N-methylpiperidine betaine (zwitterionic molecule) with hydrochloric acid (MPB) 2H·Cl, reveals that the N-methylpiperidine betaine units are hemiprotonated and form a dimeric cation through a short O·H·O hydrogen bond of 2.446(2) Å. The piperidine ring has a chair conformation with the methyl group in the axial and the –CH 2COO substituent in the equatorial position. The Me–N +–CH 2–COO unit has a gauche conformation. The investigated complex is isomorphous with (MPB) 2H·Br and pseudo-isomorphous with (MPB) 2H·I. The short hydrogen bond is described by a symmetrical double-minimum potential. The halide anions form weak C–H⋯X − hydrogen bonds with the N +–CH 2 and N +–CH 3 groups. A linear relation exists between the C–H⋯X − distance and the halide ionic radius. Eight conformers of the [(MPB) 2H] + cation and three conformers of the anion formed by (1-methyl-cyclohexyl)acetate units, [(MCHA) 2H] −, were analyzed by the B3LYP/6-31G(d,p) level of theory in order to investigate the effect of the N +⋯O electrostatic interactions on the conformation of MPB and on the short O·H·O hydrogen bond. The effect of the counter-ions on the FTIR and NMR spectra of the (MBP) 2H·X complexes is also discussed.

Crystal and molecular structure of N-methylpiperidine betaine hydrofluoride

A 1:1 complex between N-methylpiperidine betaine and hydrofluoric acid, MPB·HF, has been characterized by single crystal X-ray analysis, FTIR spectroscopy, and DFT calculations. The crystals are orthorhombic, space group Pbca, with a=11.656(2), b=9.395(2), c=16.331(3) Å. The piperidine ring adopts a chair conformation with the CH 3 group in an axial and the CH 2COO·H group in an equatorial position. In the crystal, the HF molecule is engaged in a very short O⋯H⋯F hydrogen bond (O⋯F=2.379(1) Å) with the proton most likely to reside in a single-minimum potential well shifted towards the F atom. The F − anion is engaged in three short N +⋯F − intermolecular electrostatic interactions and in several C–H⋯F contacts. Four conformers of MPB·HF (two axial and two equatorial) have been examined by the B3LYP/6-31G(d,p) method. Unlike in the crystal structure, the isolated molecule is most stable with axial CH 2COO·H group. Powder FTIR spectrum shows a broad and intense absorption in the 2500–600 cm −1 region typical for very strong hydrogen bonds.

Spectroscopic studies of N-methylpiperidine betaine complexes with phenols

Ten 1:1 crystalline complexes of N-methylpiperidine betaine with phenols (p K a from 9.55 to 0.33) were synthesised and analysed by UV–vis, 1H and 13C NMR and FTIR spectroscopies. The UV–vis spectra of complexes of moderately strong phenols show separate bands for A–H⋯B and A −⋯HB + species. Sigmoidal plots of proton and carbon chemical shifts of the N +CH 2 group versus p K a values of phenols and changes of absorption in FTIR spectra in the 3200–1800 and 1500–400 cm −1 regions additionally confirmed the A–H⋯B⇌A −⋯H–B + equilibrium in the complexes investigated.

Spectroscopic studies of N-methylpiperidine betaine complexes with phenols

Ten 1:1 crystalline complexes of N-methylpiperidine betaine with phenols (pKa from 9.55 to 0.33) were synthesised and analysed by UV–vis, 1H and 13C NMR and FTIR spectroscopies. The UV–vis spectra of complexes of moderately strong phenols show separate bands for A–H⋯B and A−⋯HB+ species. Sigmoidal plots of proton and carbon chemical shifts of the N+CH2 group versus pKa values of phenols and changes of absorption in FTIR spectra in the 3200–1800 and 1500–400 cm−1 regions additionally confirmed the A–H⋯B⇌A−⋯H–B+ equilibrium in the complexes investigated.

Crystal and molecular structure of bis( N-methylpiperidine betaine) hydroiodide

The crystal structure of 2:1 complex of N-methylpiperidine betaine with hydroiodic acid, (MPB) 2HI, reveals that the betaine units are hemiprotonated and form a dimeric cation through a short and symmetric O⋯H⋯O hydrogen bond (R(O⋯O)=2.447(1) Å). The piperidinium ring has a chair conformation with the methyl substituent in the axial and the carboxymethyl substituent in the equatorial position. The conformation of the betaine frame is identical as in the analogous (MPB) 2HBr, even though the acidic proton is attached to the opposite carboxylate O atom. This remarkable difference can be viewed as a 180° rotation of the –COO·H group or as a proton jump. The framework of the I −/H + centers is largely unchanged but the betaine units swivel around the H + sites to bring the alternate carboxylate O atoms into the O⋯H⋯O bridge, resulting in a pseudo-isomorphous relation between these two crystals. In its altered environment, the I − anion rests in an enlarged hydrophobic cavity where it accepts a number of more regularly arranged C–H⋯I hydrogen bonds. Two conformers ( I and II) of the [(MPB) 2H] + cation were analyzed by the B3LYP/6-31G(d,p) level of theory. In I the N + atom is closer to the O⋯H group, while in II it is closer to the CO group. The calculated O⋯O distances are shorter than in the crystal. FTIR spectrum of (MPB) 2HI shows a broad and intense νOHO absorption in the 1500–400 cm −1 range, which is similar to that of type A acid salts of carboxylic acids and other 2:1 betaine complexes with mineral acids.

Crystal and molecular structure of N-methylpiperidine betaine hydrochloride

A 1:1 complex between N-methylpiperidine betaine and hydrochloric acid, MPBH·Cl, has been characterized by single crystal X-ray analysis, FTIR spectroscopy, and DFT calculations. The crystals are monoclinic, space group P2 1/ n, with a=6.0644(3), b=13.0220(6), c=12.7653(7) A ̊ , β=101.925(5)°. The piperidine ring adopts a chair conformation with the –CH 2COOH group in an axial and the-CH 3 group in an equatorial position. In the crystal, the Cl −anion is engaged in a medium-strong hydrogen bond with the COOH group (O–H⋯Cl −=2.9503(7) Å), in several C–H⋯Cl − contacts and, additionally, in three N +⋯Cl −intermolecular interactions. Four conformations (axial and equatorial, both protonated and unprotonated) of MPBHCl were examined by the B3LYP/6-31G(d,p) method. The calculated structure of MPBH·Cl(ax) is very similar to that in the crystal, except the N(1)–C(8)–C(9)–O(1) and N(1)–C(8)–C(9)–O(2) units, which are planar in the crystal but nonplanar in the isolated molecule. Powder FTIR spectra of MPBH·Cl and its deuterated analogue (MPBD·Cl) were measured and assignments of the observed bands to vibrations of the hydrogen bond and to internal vibrations are proposed.

FTIR, 1H and 13C NMR spectra of 1:1 complexes of 1-piperidineacetic acid and N-methylpiperidine betaine with mineral acids

Syntheses of 1:1 complexes of 1-piperidineacetic acid (PAA) and N-methylpiperidine betaine (MPB) with HCl, HBr, HI, HNO 3, HClO 4, HBF 4 and their 1H and 13C NMR spectra in D 2O and powdered FTIR spectra are described. The difference between the spectra of theses two series of complexes are discussed and analysed in order to determine the effect of the N–H replacement by N–CH 3 group.

Bis( N-methylpiperidine betaine) hydrobromide: crystal structure and hydrogen bonding

Bis( N-methylpiperidine betaine) hydrobromide, (MPB) 2HBr, was synthesised and its crystal structure has been solved by X-ray diffraction at 100 K and refined to R=0.020. The crystals are monoclinic, space group C2/ c, a=22.885(2), b=7.4498(5), c=10.6896(7) Å, β=92.89(1)°, V=1820.1(2) Å 3, Z=4. The piperidine ring adopts a chair conformation with the N +–CH 2COO·H group in an equatorial and the N +–CH 3 group in an axial position. A pair of betaine molecules are bridged by a proton to form a dimeric cation featuring a very short centrosymmetric hydrogen bond (O⋯O distance 2.445(2) Å). FTIR spectra of (MPB) 2HBr and (MPB) 2HCl show very similar broad absorption in the 1000–500 cm −1 region typical for very short hydrogen bonds. In the second and fourth derivative spectra, the carbonyl band appears as a single band. PM3 calculations for the dimeric cation reproduced a hydrogen bond that is much shorter than in the crystal and slightly asymmetric, while B3LYP predicts O⋯O distance that is comparable to that in the crystal, and corresponding to a symmetrical or asymmetrical hydrogen bond, depending on the conformation of the carboxymethyl substituent (equatorial–equatorial or axial–axial, respectively).

Conformers and hydrogen bond transformations in N-methylpiperidine betaine 2,4-dinitrophenolate crystals

The molecular structure of a complex of N-methylpiperidine betaine with 2,4-dinitrophenol has been determined by X-ray diffraction. The crystals are orthorhombic, space group Fdd2 with a=41.854(8), b=44.000(9), c=6.9270(10) A ̊ , Z=32, V=12757(4) A ̊ 3. Such an exceptionally large cell is due to high symmetry of the crystal and to the presence of two crystallographically non-equivalent complexes, denoted as (a) and (b). The symmetry-independent dinitrophenolate molecules clearly differ in conformation, which modify their electronic structure and affects the hydrogen bonds. The OHO intermolecular hydrogen bonds are very short, with O⋯O distances of 2.419(6) and 2.441(6) Å. We have established that the hydrogen atom is closer to the phenol molecule in complex (a), while it is shared between the oxygen atoms of the carboxylate group of betaine and phenolate ion in complex (b), which is consistent with the conformations of the molecules. FTIR spectrum shows a broad absorption in the 2000–400 cm −1 region characteristic of such short hydrogen bonds.

Crystal and molecular structure of N-methylpiperidine betaine hydrobromide

The molecular and crystal structure of N-methylpiperidine betaine hydrobromide, MPBHBr, has been solved by X-ray diffraction methods at 100K and refined to the R=0.017 (I>2σ(I)). The crystals are monoclinic, space group P21/c, a=6.193(1), b=13.275(3), c=13.056(3)Å, β=103.38(3)°, V=1044.2(4)Å3, Z=4. Piperidine ring adopts a chair conformation with the CH2COOH group in an axial and the CH3 group in an equatorial position. The carboxylic group is engaged in a weak hydrogen bond with the bromide ion, O–H⋯Br− (Br−⋯O 3.130(1)Å). Powder FTIR spectrum was measured and assignments of the observed bands to vibrations of the hydrogen bond are proposed. In the crystal, the hydroxy proton in the COOH group is in syn conformation relative to the CO bond, while in the PM3-optimized structure it is in anti.

Conformational preferences of isostructural N-methylpiperidine betaine and (1-methylcyclohexyl)acetic acid studied by PM3 and B3LYP calculations. The effect of electrostatic interactions on the rotation barrier

PM3 conformational analysis has been carried out on the axial and equatorial N-methylpiperidine betaine (N-carboxymethyl-N-methylpiperidinium inert salt), MPB, and (1-methylcyclohexyl)acetic acid, MCHA. The terms axial and equatorial refer to the positions of CH2COO(H) substituents. The rotation barriers for H3C–N+–CH2–COO− and H3C–C–CH2–COOH units in the axial and equatorial stereoisomers are 9.9 and 6.1kcal/mol for MPB and 3.9 and 2.4kcal/mol for MCHA, respectively. An increase of the rotation barriers on going from MCHA to MPB is result of appearance of the Coulombic interactions between the charged groups in the latter compounds. The intramolecular C–H⋯O hydrogen bonding plays a minor role in determining the conformation. Four conformers of MPB have been analyzed by B3LYP level calculation with 6-31G(d,p) and 6-311++G(d,p) basis sets and the results demonstrate that the most stable is the axial-gauche and the least stable is the axial-anti conformer.

Crystal structure and vibrational spectrum of N-methylpiperidine betaine hexafluorosilicate

The crystal structure of N-methylpiperidine betaine hexafluorosilicate has been determined by X-ray diffraction at 100K. The complex consists of two protonated betaines and one SiF62− anion. In both cations the piperidinium ring assumes a chair conformation, but the CH2COOH substituent is axial in one cation and equatorial in the other. Two O–H⋯F hydrogen bonds are present in the crystal, R(O⋯F)=2.565(1) and 2.617(1)Å. The FTIR spectrum shows the νOH modes in the 3300–2300cm−1 region and two νCO bands, at 1749 and 1726cm−1. An assignment of the observed bands due to vibrations of the SiF62− ion is proposed. In the crystal, the hydroxy protons in both COOH groups are in syn conformation, while in an PM3-optimized model (II) they are anti.

Conformational analysis of N-methylpiperidine betaine studied by X-ray diffraction, FTIR spectroscopy and ab initio calculations

N-methylpiperidine betaine crystallized either as anhydrous or monohydrate. The crystal of the anhydrous form are monoclinic, space group C2/c, a=18.512(2) Å, b=11.3017(10) Å, c=9.2212(10) Å, β=118.48(1)o. The molecule in crystals has a conformation with the N+ ⋯O intermolecular distance of ca. 2.90 Å. Structures of isolated molecule optimized with BLYP and MP2 methods are very similar to this observed in the crystal.