From Cyclic Ribopyranose to Furfural-New Insight and New Concept Volume 56- Issue 1

Iwan Iwanov¹*, Denitsa Yancheva², Nikolay Kaloyanov¹, Nikolay Lumov², Armen Sargsyan³ and Mihail Neykov¹

• ¹University of Chemical Technology and Metallurgy, Department of Organic Chemistry, Science and Research Unit, Bulgaria
• ²Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Bulgaria
• ³Scientific and Production Center “Armbiotechnology” NASRA, 14 Gyurjyan str., Armenia

Received: March 20, 2024; Published: April 12, 2024

*Corresponding author: Iwan Iwanov, University of Chemical Technology and Metallurgy, Department of Organic Chemistry, Science and Research Unit, KL OHRIDSKY BOULEVARD 8, Sofia 1756, Bulgaria

DOI: 10.26717/BJSTR.2024.56.008794

Abstract PDF

The current Organic Chemistry lacks systematic ribopyranose-furfural transformation (10 steps), supported by any spectra analysis or computational calculation of charge distribution on the chain. Our idea is that first protonation and dehydratation will happen on the HO-group in cyclic ribopyranose, which forms the most stable carbocation after being deleted.

Keywords: Cyclic Ribopyranose; Full Mechanism; Induction Effect; IR Spectrum; Charge Calculation

Ribose is a simple sugar with Chemical formula C5H10O5. The naturally occurring form, D- ribose, is a component of the ribonucleotides from which RNA is built, and so this compound is necessary for coding, decoding, regulation and expression of genes. L-ribose is an unnatural sugar that was first prepared by Emil Fischer and Oscar Piloty in 1891[1]. Like most sugars, ribose exists as a mixture from equal parts of cyclic forms and linear structure, especially in aqueous solution [2]. For D-ribose, we have five structures in water: open chain, α-D-ribopyranose, β-D-ribopyranose, α-D-ribofuranose, and β-D- ribofuranose. For L-ribose, we have open chain, α-L-ribopyranose, β-L-ribopyranose, α-L-ribofuranose, and β-L-ribofuranose in aqueous solution. Our team has decided to verify the ribopyranose-furfural transformation from 2016 [3] by investigation on ribopyranose carbocations, calculation of their positive charges, assessment of their stabilities and induction effect analysis on reaction steps.

Infrared measurements. Attenuated Total Reflectance Fourier-Transform Infrared (ATR-FTIR) spectra of the D-ribose, furfural and the reaction products were measured on a Bruker Invenio R spectrometer, equipped with a diamond crystal ATR accessory at resolution 2 cm-1 accumulating 100 scans. Spectrum of air was used as a background. In order to measure the spectrum, the solid D-ribose was placed directly on the ATR crystal and pressed by a metal tip. The furfural was studied as a film on the surface of the ATR crystal, while the reaction products were deposited on glass plates, dried in desiccator and pressed to the surface of the ATR crystal in order to obtain the IR spectra. Computational details. The Gaussian 09 software [4] was used to carry out density functional theory (DFT) calculations for molecular structure optimization and vibrational frequency analysis. The geometry of ribose and its carbocations, included several possible isomers, was optimized by applying the Becke’s three-parameter hybrid functional (B3LYP) [5] in conjunction with 6-311++G(d,p) valence double-zeta polarized basis set [6,7]. The solvent (water) was acconted in the computations based on the IEF-PCM (Integral Equation Formalism Polarizable Continuum Model) solvation model implemented in the Gaussian 09 software package [8,9].

The optimized structures were confirmed as minima on the potential energy hypersurface by analytic vibrational frequency computations at the same level of theory. For all compounds and radicals, energy was minimized and the lowest energy structure was used in all calculations without any geometry or symmetry constraints. All calculations were performed using Gaussian 09 program package at the level of DFT/B3LYP with a basis set 6-31-G (d,p) [10] (Table 1). Cambridge Soft Chem 3D package of Chem Office 12 was used for calculation of charge distribution by Hűckel as well as for visualization of models. Infrared spectroscopy of the reaction products during the conversion of D-ribopyranose into furfural. The conversion of D-ribose into furfural was monitored by IR spectral study of the reaction products obtained at different stages of the reaction. The conversion was performed in solution by the procedure: 1g of D- ribose was dissolved in 15 ml mixture of conc HCl and water in portion 7/18. The reaction goes in four hours-1 hour at room temperature and 3 hours at 60 degrees Celsius at stirring. Small portions of the reaction mixture were taken at 10, 20, 30 and 50 min and deposited dropwise on glass plates. The films were dried in desiccator and then ATR-FTIR spectra were measured on a diamond ATR accessory. ATR- FTIR spectrum of the initial solution (0 min), containing only D-ribose, was measured as starting point and shown in Figure 1a, as it could be seen, corresponds over 80% to the pure D-ribose spectrum shown in Figure 1b.

Figure 1

Table 1: Huckel charges of cyclic ribopyranose cations.

Only in carbocation 1 we have two carbon atoms on both sides of the positive charge (denoted as 1-2 and 1’-2’), which implies the highest stability, confirmed by the lowest positive charge on deleted HO-group of carbocation 1. Cyclic ribopyranose transformation to furfural is going in 10 steps as presented in Figure 2.

• Steps 1,2: Protonation of the hydroxyl group corresponding to carbocation 1 and release of a water molecule. Step 3: Catalyst deprotonation and recovery. Here a hydrogen proton can be released from both sides of the positive charge: from C2 or from C4. Because of the strong positive induction effect of the methylene group, it serves as a conductor for withdrawing electron density from neighboring atoms or groups of atoms. Therefore, the O-atom of the pyran ring withdraws more electron density from C4 compared to C2, and accordingly, the H-atom at C4 is more mobile and more easily cleaved.

• Steps 4,5: Protonation of the hydroxyl group at C2 as it is closer to the double bond, which is highly electrophilic and release of a water molecule.

• Step 6. Catalyst deprotonation and recovery. Here there are three possibilities for releasing a hydrogen proton: from C1, from C3 or form C5. Because of its sp2-hybrid state, C-H bond at C3=C4 double bond is the strongest of all C-H bonds in the pyran ring and the H atom at C3 is strongly bonded and cannot be easily cleaved. The other two possibilities are C1 or C5, which are adjacent to the pyran O-atom, but C5 is closer to the most electronegative element in the pyran ring, which is the double bond at C3=C4. Therefore the two H-atoms at C4 are more mobile than the H-atom at C3 and one of them is released as a proton. At the same time, the ring opens forming a di-hydroxy aldehyde.

• Step 7: Protonation of the HO-group at C4.

• Step 8: Dehydration.

• Step 9: Intramolecular nucleophilic attack of HO-group (the only one after dehydration three times) to positive charge and formation of furfural ring.

• Step 10: Deprotonation and turning back the final catalyst.

The lowest charge on C-6 of Carbocation-1 indicates the highest charge distribution along the chain and the highest stability of Carbocation-1 Figure 3. After first deprotonation on C-6 and Carbocation-1 appearance, we have a completely new chemical structure and we can suppose what happens next as presented in Figure 2.

Figure 2

Figure 3

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