Tetrel , Chalcogen , and Charge-Assisted Hydrogen Bonds in 2-( ( 2-Carboxy-1-( substituted )-2-hydroxyethyl ) thio ) Pyridin-1-ium Chlorides

Reaction of 2-chloro-2-(diethoxymethyl)-3-substitutedoxirane or 1-chloro-1-(substituted) -3,3-diethoxypropan-2-one with pyridine-2-thiol in EtOH at 25 ◦C yields 3-(diethoxymethyl)-3hydroxy-2-substituted-2,3-dihydrothiazolo[3,2-a]pyridin-4-ium chlorides, which subsequently, in MeCN at 85◦C, transforms into ring-opening products, 2-((2-carboxy-1-(substituted) -2-hydroxyethyl)thio)pyridin-1-ium chlorides. The tetrel (C···O) and chalcogen (S···O) bonds are found in the structures of 5 and 6, respectively. Compound 6 is also present in halogen bonding with a short O···Cl distance (3.067 Å). Both molecules are stabilized in crystal by tetrel, chalcogen, and multiple charge-assisted hydrogen bonds.

On the other hand, the charge-assisted hydrogen bonding (CAHB), viz.interactions of the X(+)-H•••Y(−) type with the X-H donor belonging to a cation and the Y acceptor belonging to an anion, constitutes a particularly powerful tool used in the synthesis and design of new compounds [9,20,21].CAHBs can control a great variety of synthetic operations involving molecules with groups exhibiting acid-base properties [20,21].Due to the strength and directionality of the CAHB, this type of noncovalent interaction has an impact on the synthesis of coordination compounds [9], crystal engineering [20][21][22][23], etc.In most cases, due to the additional electrostatic interactions involved, CAHBs are stronger in comparison to normal hydrogen bonds.
On the other hand, α-hydroxy carboxylic acids are versatile and powerful intermediates for the synthesis of various chiral compounds with unique properties [24][25][26][27].Furthermore, the functionalization of α-hydroxy carboxylic acids with 2-tiopyridine (expected chalcogen bond donor) moiety can increase their bioactivity, donor sites towards coordination, etc.
On the other hand, the charge-assisted hydrogen bonding (CAHB), viz.interactions of the X(+)-H•••Y(−) type with the X-H donor belonging to a cation and the Y acceptor belonging to an anion, constitutes a particularly powerful tool used in the synthesis and design of new compounds [9,20,21].CAHBs can control a great variety of synthetic operations involving molecules with groups exhibiting acid-base properties [20,21].Due to the strength and directionality of the CAHB, this type of noncovalent interaction has an impact on the synthesis of coordination compounds [9], crystal engineering [20][21][22][23], etc.In most cases, due to the additional electrostatic interactions involved, CAHBs are stronger in comparison to normal hydrogen bonds.
On the other hand, α-hydroxy carboxylic acids are versatile and powerful intermediates for the synthesis of various chiral compounds with unique properties [24][25][26][27].Furthermore, the functionalization of α-hydroxy carboxylic acids with 2-tiopyridine (expected chalcogen bond donor) moiety can increase their bioactivity, donor sites towards coordination, etc.
Due to the thermodynamic stability of 1-4, the expected acyclic products, 2-((1-(substituted)-3,3-diethoxy-2-oxopropyl)thio)pyridin-1-ium chlorides (I), were not observed (Scheme 1).The structures of 1-4 were fully characterized by 1 H and 13 C NMR, ESI-MS, as well as elemental and X-ray analysis (for 1).In the 1 H NMR spectra of 1-4, the CHS and OH protons are observed at δ 4.37-4.54and 9.64-9.98,respectively.Elemental analyses (see ESI section (4) support the formulations, which are also proved by X-ray crystallography for 1 (Figure 1).The structures of 5 and 6 were also established by X-ray diffraction.In the 1  These compounds may stabilize as synor anti-isomers, depending on the nature of the involved intermolecular noncovalent interactions (Figures 2-5).For example, 5 is stabilized as a syn-isomer whereas 6 is stabilized as an anti-isomer in the solid state.In the latter compound also presents an additional halogen bonding with a short O•••Cl distance (3.067 Å) that is shorter than twice the sum of the van der Waals radii of the interacting atoms (O + Cl = 1.52 + 1.75 = 3.27 Å) [28] (Figure 5), and with the O•••ClC Ar angle of 162.86 • .A Cl − in both compounds provides negative charge-assisted hydrogen bonds with hydroxylic and carboxylic-OH, asymmetric SCH, and aromatic CH protons (Figure 4).Moreover, 5 and 6 contain an intramolecular 1,4 S•••O synthon with the distance of 2.814 and 2.958 Å, respectively, suggesting that there is a strong chalcogen bonding between the electron-donating hydroxyl O atom and the acceptor S atom of the thioether, as compared with the sum of the van der Waals radii of 3.32 Å [28].Moreover, these distances are shorter than the corresponding distance of

Materials and Instrumentation
All the chemicals were obtained from commercial sources (Aldrich) and used as received.Carbon, hydrogen, and nitrogen elemental analyses were conducted using a "2400 CHN Elemental Analyzer" (Perkin-Elmer, MA, USA).The infrared spectra (4000-400 cm −1 ) were recorded on a Vektor 22 (Bruker, Bremen, Germany) instrument in KBr pellets.The 1 H and 13 C NMR spectra were recorded at room temperature on a Bruker Avance II + 300 (UltraShield TM Magnet, Bruker, Ettlingen,

Materials and Instrumentation
All the chemicals were obtained from commercial sources (Aldrich) and used as received.Carbon, hydrogen, and nitrogen elemental analyses were conducted using a "2400 CHN Elemental Analyzer" (Perkin-Elmer, MA, USA).The infrared spectra (4000-400 cm −1 ) were recorded on a Vektor 22 (Bruker, Bremen, Germany) instrument in KBr pellets.The 1 H and 13 C NMR spectra were recorded at room temperature on a Bruker Avance II + 300 (UltraShield TM Magnet, Bruker, Ettlingen,

Materials and Instrumentation
All the chemicals were obtained from commercial sources (Aldrich) and used as received.Carbon, hydrogen, and nitrogen elemental analyses were conducted using a "2400 CHN Elemental Analyzer" (Perkin-Elmer, MA, USA).The infrared spectra (4000-400 cm −1 ) were recorded on a Vektor 22 (Bruker, Bremen, Germany) instrument in KBr pellets.The 1 H and 13 C NMR spectra were recorded at room temperature on a Bruker Avance II + 300 (UltraShield TM Magnet, Bruker, Ettlingen,

Materials and Instrumentation
All the chemicals were obtained from commercial sources (Aldrich) and used as received.Carbon, hydrogen, and nitrogen elemental analyses were conducted using a "2400 CHN Elemental Analyzer" (Perkin-Elmer, MA, USA).The infrared spectra (4000-400 cm −1 ) were recorded on a Vektor 22 (Bruker, Bremen, Germany) instrument in KBr pellets.The 1 H and 13 C NMR spectra were recorded at room temperature on a Bruker Avance II + 300 (UltraShield TM Magnet, Bruker, Ettlingen, Germany) spectrometer operating at 300.130 and 75.468MHz for proton and carbon-13, respectively.The chemical shifts are reported in ppm using tetramethylsilane as the internal reference.Electrospray mass spectra (ESI-MS) were run with an ion-trap instrument (Varian 500-MS LC Ion Trap Mass Spectrometer) (Varian, CA, USA) equipped with an electrospray ion source.For electrospray ionization, the drying gas and flow rate were optimized according to the particular sample with 35 psi nebulizer pressure.Scanning was performed from m/z 0 to 1100 in methanol solution.The compounds were observed in the positive mode (capillary voltage = 80-105 V).

Synthesis of
one (0.75 mmol) was dissolved in 10 mL ethanol at room temperature and 0.11 g (0.75 mmol) pyridine-2-thiol was added.The reaction mixture was stirred for 15 hours (as monitored by thin layer chromatography TLC), then the solvent was removed under reduced pressure, and the was washed with acetone.Recrystallization from ethanol gave pure products.

X-ray Analysis
X-ray diffraction patterns of 1, 5, and 6 were collected using a Bruker SMART APEX-II CCD area detector equipped with graphite-monochromated Mo-Kα radiation (λ = 0.71073 Å) at room temperature.Absorption correction was applied by SADABS [30,31].The structure was solved by direct methods and refined on F 2 by the full-matrix least-squares method using Bruker's SHELXTL-97 [32].All non-hydrogen atoms were refined anisotropically.The details of the crystallographic data are summarized in Table 1.Crystallographic data for the structural analysis have been deposited to the Cambridge Crystallographic Data Center (CCDC 1536797, 1536798 and 1536799 for 1, 5, and 6, respectively).Copy of this information can be obtained free of charge from The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax: (+44) 1223-336033; E-mail: deposit@ccdc.cam.ac.uk or www.ccdc.cam.ac.uk/data_request/cif).