N,N,N-Trimethyl-N-(methyl 5-de­oxy-2,3-O-iso­propyl­idene-β-d-ribo­furan­osid-5-yl)ammonium 4-methyl­benzene­sulfonate sesquihydrate

Barbara Dmochowska; Karol Sikora; Jaroslaw Chojnacki; Wieslaw Wojnowski; Andrzej Wiśniewski

doi:10.1107/S1600536813014797

. 2013 Jun 8;69(Pt 7):o1019–o1020. doi: 10.1107/S1600536813014797

N,N,N-Trimethyl-N-(methyl 5-deoxy-2,3-O-isopropylidene-β-d-ribofuranosid-5-yl)ammonium 4-methylbenzenesulfonate sesquihydrate

Barbara Dmochowska ^a, Karol Sikora ^b, Jaroslaw Chojnacki ^c,^*, Wieslaw Wojnowski ^c, Andrzej Wiśniewski ^a

PMCID: PMC3772458 PMID: 24046601

Abstract

The structure of the title compound, [C₁₂H₂₄NO₄][C₇H₇O₃S]·1.5H₂O, contains alternating layers parallel to (001) of hydrophobic and polar character, stabilized by C—H⋯O hydrogen bonding. The furan ring adopts an envelope conformation with the C(OMe) atom as the flap, and the dioxolane ring is twisted about one of the O—C(methine) bonds. A comparison to related compounds is presented. The tosylate-O atoms were disordered over two positions with the major component having a site occupancy factor = 0.566 (12). The structure was refined as a rotary twin with regard to rotation about the c axis with the contribution of the second component being 0.0048 (6). Solvate water molecules are highly disordered and were removed using the SQUEEZE procedure; the unit cell characteristics take into account the presence of the disordered solvent. High-resolution ¹H and ¹³C NMR spectroscopic data are also presented.

Related literature

For background to quaternary ammonium compounds, see: Jones (1984 ▶); Śliwa (1996 ▶); Sajomsang et al. (2009 ▶); Obłąk & Gamian (2010 ▶); Binks et al. (2011 ▶); Singh et al. (2009 ▶); Cruz-Guzman et al. (2005 ▶); Rabea et al. (2003 ▶); Belalia et al., 2008 ▶; McDonnell & Russell (1999 ▶); Boethling (1984 ▶); Levinson (1999 ▶); Cross & Singer (1994 ▶). For QAC sugar derivatives, see: Abel et al. (2002 ▶); Blizzard et al. (2002 ▶); Honda et al. (1988 ▶); Thomas et al. (2009 ▶); Maslov et al. (2010 ▶); Dmochowska et al. (2006 ▶, 2009 ▶, 2011 ▶); Pellowska-Januszek et al. (2004 ▶); Skorupa et al. (2004 ▶). For related synthetic methods, see: Gosh & Liu (1996 ▶); Sairam et al. 2003 ▶; Sarabia-Garcia & Lopez-Herrera (1996 ▶); Dibrov et al. (2010 ▶). For ring puckering analysis, see: Cremer & Pople (1975 ▶). graphic file with name e-69-o1019-scheme1.jpg

Experimental

Crystal data

C₁₂H₂₄NO₄ ⁺·C₇H₇O₃S⁻·1.5H₂O
M _r = 444.53
Monoclinic,
a = 11.4896 (15) Å
b = 7.9311 (11) Å
c = 13.4853 (17) Å
β = 111.619 (12)°
V = 1142.4 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 200 K
0.37 × 0.2 × 0.17 mm

Data collection

Kuma KM4CCD (Sapphire2 detector) diffractometer
26053 measured reflections
4481 independent reflections
4325 reflections with I > 2σ(I)
R _int = 0.038

Refinement

R[F ² > 2σ(F ²)] = 0.051
wR(F ²) = 0.139
S = 1.07
4481 reflections
283 parameters
40 restraints
H-atom parameters constrained
Δρ_max = 0.40 e Å⁻³
Δρ_min = −0.31 e Å⁻³
Absolute structure: Flack & Bernardinelli (1999 ▶)
Flack parameter: 0.08 (12)

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 ▶); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2006 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶) and WinGX (Farrugia, 2012 ▶); molecular graphics: Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶) and publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813014797/tk5228sup1.cif

e-69-o1019-sup1.cif^{(30.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813014797/tk5228Isup2.hkl

e-69-o1019-Isup2.hkl^{(215.1KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C13—H13A⋯O28A ⁱ	0.98	2.45	3.412 (15)	167
C13—H13B⋯O28A ⁱⁱ	0.98	2.44	3.308 (13)	148
C14—H14B⋯O26A ⁱ	0.98	2.30	3.251 (9)	163
C14—H14C⋯O27A ⁱⁱⁱ	0.98	2.22	3.161 (8)	162
C15—H15C⋯O5	0.98	2.41	2.964 (4)	115
C19—H19⋯O26A	0.95	2.26	2.712 (9)	108

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

This work was partially financed by grant DS/530–8451-D193–13. We thank Ms Iwona Rabczuk for some of the experimental work and M. Sc. Leszek Łobocki for measurements of mass spectra (MALDI TOF).

supplementary crystallographic information

Comment

Scientists the world over have been interested in quaternary ammonium compounds (QACs) for over a hundred years (Jones, 1984; Śliwa, 1996, Sajomsang et al., 2009; Obłąk & Gamian, 2010). These salts display both inorganic properties (e.g. their excellent solubility in water) and organic ones, and their hydrophilic properties are due to their ionic nature. They are present in fabric softeners and corrosion inhibitors (Binks et al., 2011; Singh et al., 2009), they act as fungicides, pesticides and insecticides (Cruz-Guzman et al., 2005), they exhibit antibacterial and antifungal activities and are therefore constituents of antimicrobial drugs (Rabea et al., 2003; Belalia et al., 2008; McDonnell & Russell,1999) and they are ingredients of shampoos and hair conditioners (Boethling, 1984; Levinson, 1999; Cross & Singer, 1994). Without doubt, QACs are used worldwide in industry, agriculture, healthcare and the home. Recent years have witnessed a resurgence of interest in the synthesis of QACs, especially their sugar derivatives, which have potential biological properties (Abel et al., 2002; Blizzard et al., 2002; Honda et al., 1988; Thomas et al., 2009; Maslov et al., 2010).

One of our current research objectives is to find a correlation between the structure of the substituents around the quaternary nitrogen atom and the biological activity of the compounds concerned (Dmochowska et al., 2011; Pellowska-Januszek et al., 2004). The synthesis of QACs possessing a substituent that would increase the solubility of these salts appears to be interesting, and the incorporation into the QAC molecule of such a natural entity as a sugar unit could be very effective.

Synthetic work

Our research group synthesized numerous N-[(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol)-5-yl]aminium tosylates (Dmochowska et al., 2006; 2009; Skorupa et al., 2004). We thought it would be very interesting to examine the synthesis of analogous QACs with methyl 2,3-O-isopropylidene-β-D-ribofuranoside and the influence of the O-Me substituent at the anomeric carbon atom on the course of the quaternization reaction at C-5 and on the conformation of the furanoic ring.

The synthesis of N-[(methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl]aminium tosylates began with commercially available D-ribose (1), Fig. 1, which was converted to methyl 2,3-O-isopropylidene-β-D-ribofuranoside (2), (Gosh & Liu 1996; Sairam et al., 2003). Next, the hydroxyl group at C-5 of compound 2 was activated with p-toluenesulfonyl chloride using a well known method (Sarabia-Garcia & Lopez-Herrera, 1996). The idea was to investigate the reactions of methyl 2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside (3) with tertiary amines, viz. triethylamine, trimethylamine, 4-(N,N-dimethylamino)pyridine, isoquinoline, 2-methylpyridine and pyridine. All the newly synthesized N-[(methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl]aminium tosylates were water-soluble. Their structures were determined by NMR. Here we report the X-ray structure of the product with NMe₃.

The reaction of 3 with 33% ethanolic solution of NMe₃ (70° C, 48 h) yielded N-[(methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl]-N,N,N-trimethylammonium tosylate (4), (yield 67%). Its identity was also confirmed by ¹H and ¹³C NMR spectra.

Description of the X-ray structure

Crystals belong to the monoclinic system, space group P2₁. The asymmetric unit of (4) contains one tertiary ammonium cation and one tosyl anion and one and half molecules of solvate water (Fig. 2). The charged parts of both ions are directed towards the middle of the cell, forming a hydrophilic layer, perpendicular to the c axis (Fig. 3). The structure is reinforced by non-conventional C—H···O hydrogen bonds, which are formed perhaps due to the strong acceptor properties of anionic oxygen atoms (see Table 1). The region of disordered solvent is located in the hydrophilic layer and use of SQUEEZE recovered 16.8 e^- from a void of volume V = 101.8 Å³. Electron density, found in the void, was interpreted as coming from one and half molecules of water per one ionic pair. Naturally, this leads to formation of additional hydrogen bonds in the hydrophilic layer.

Ring puckering analysis (Cremer & Pople 1975; Spek, 2009) of 4 shows that the five-membered furan ring adopts the envelope C1 – endo conformation (with Q = 0.301 (3) Å, φ= 227.4 (6)°, P = 314.5 (3)° and τ_m (C2—C3) = 32.8 (2)°). Noteworthy, C1 atom is substituted by the methoxy group which may be the reason for increased stability of the conformation. In the analogous compound, substituted by hydrogen at position 1, not a carbon atom but an oxygen atom defined the envelope (see Table 2). Apparently, the opposite is true for compounds without the protection of OH groups. However, electrostatic forces also contribute significantly to the free energy balance, leading in the case of iodide to formation of the twisted furan ring.

The oxolane ring, O6—C2—C3—O8—C7, is best described as having the twisted conformation about the O6—C2 bond (with Q = 0.319 (3) Å, φ = 11.5 (6)°, P = 100.3 (3)° and τ_m (C3—O8) = 34.9 (2)°). To facilitate comparisons, we also included data on, published recently, trans-3,4 dihydroxy substituted analogue, (3,4-dihydroxyoxolan-2-yl)methyl 4-methylbenzenesulfonate (Dibrov et al., 2010) whose conformation was not described by the authors (Q = 0.397 Å, φ = 245.4°, P = 333.7° and τ_m (C1—C8) = 41.7°).

Experimental

General remarks

Commercial D-ribose (Fluka) was used. All reactions were monitored by thin-layer chromatography (TLC) on Kieselgel 60 F₂₅₄ Silica Gel plates (E. Merck, 0.20 mm thickness) using eluent system (v/v) 3:1 CHCl₃ – MeOH. The spots were detected by spraying with 5% ethanolic H₂SO₄ and charring. ¹H and ¹³C NMR spectra (CDCl₃, internal Me₄Si) on a Varian Mercury 400 (400.49/100.70 MHz) instrument; positive-ion mode MALDITOF mass spectra on a Bruker Biflex III spectrometer with α-cyano-4-hydroxycinnamic acid as the matrix.

Synthesis ofN-[(methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl]-N,N,N-trimethylammonium tosylate (4)

Methyl 2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside (3) (150 mg, 0.42 mmol) was dissolved in 33% ethanolic solution of NMe₃ (0.31 ml). The solution was stored for 48 h in a screw-capped ampoule at 70°C, then the solvents were evaporated to dryness. The residue was dissolved in H₂O, then extracted with CHCl₃. The aqueous layer was evaporated and dried to yield quaternary aminium compound, which was recrystallized from 2-butanone, 4 (117.5 mg, 67%); M.pt: 348–351 K; [α]_D²⁰ -12.0 (c 1/5, H₂O); ¹H-NMR (D₂O): δ 7.71–7.39 (2 d, each 2H, Ph), 5.22 (s, 1H, H-1), 4.89 (dd, 1H, H-3, J_2,3 5.6; J_3.4 1.4), 4.81 (d, 1H, H-2, J_2,3 6.0), 4.77 (m, 1H, H-4, J_4,5' 9.6), 3.69 (dd, 1H, H-5, J_4,5 2.6, J_5,5' 14.0), 3.55 (dd, 1H, H-5', J_4,5' 9.6), 3.49 (s, 3H, –OCH₃), 3.26 (s, 9H, N(CH₃)₃), 2.42 (s, 3H, PhCH₃), 1.56- 1.40 (2 s, each 3H, C(CH₃)₂); ¹³C NMR (H₂O) δ 129.66-125.70 (C, Ph), 114.08 (C, C(CH₃)₂), 110.42 (C-1), 83.86 (C-2), 83.08 (C-3), 81.16 (C-4), 68.91 (C-5), 56.32 (OCH₃), 54.26 (N(CH₃)₃), 25.62- 24.02 (C, C(CH₃)₂), 20.70 (C, PhCH₃); MALDI TOF– MS (CCA): m/z 246 ([M-OTs]⁺).