Acceleration and Deceleration Factors on the Hydrolysis Reaction of 4,6-O-Benzylidene Acetal Group

Abstract

The benzylidene acetal group is one of the most important protecting groups not only in carbohydrate chemistry but also in general organic chemistry. In the case of 4,6-O-benzylidene glycosides, we previously found that the stereochemistry at 4-position altered the reaction rate constant for hydrolysis of benzylidene acetal group. However, a detail of the acceleration or deceleration factor was still unclear. In this work, the hydrolysis reaction of benzylidene acetal group was analyzed using the Arrhenius and Eyring plot to obtain individual parameters for glucosides (Glc), mannosides (Man), and galactosides (Gal). The Arrhenius and Eyring plot indicated that the pre-exponential factor (A) and ΔS ⧧ were critical for the smallest reaction rate constant of Gal among nonacetylated substrates. On the other hand, both E a /ΔH ⧧ and A/ΔS ⧧ were influential for the smallest reaction rate constant of Gal among diacetylated substrates. All parameters obtained suggested that the rate constant for hydrolysis reaction was regulated by protonation and hydration steps along with solvation. The obtained parameters support wide use of benzylidene acetal group as orthogonal protection of cis-and trans-fused bicyclic systems through the fast hydrolysis of the trans-fused benzylidene acetal group.

Studies for Elucidation of Oligosaccharide Functions of Glycoproteins

“…As shown here, using Arrhenius and Eyring plot analysis, we revealed the contribution of the thermodynamic parameters ΔH , TΔS , and ΔG in the hydrolysis reaction of the benzylidene acetal groups of monosaccharides. 16…”

Simultaneous Characterization of Reaction Kinetics and Enthalpy by Calorimetry Based on Spatially Resolved Temperature Profile in Flow Reactors

“…Monitoring the progress of a reaction over time is one of the methods for framing a kinetic rate equation (Figure a) . To analyze reaction systems in detail, Arrhenius plots are constructed to determine the activation energy and frequency factor, which are vital for optimizing reactions . However, these methods are time-consuming because they require repeated sampling and quantification.…”

“…2 To analyze reaction systems in detail, Arrhenius plots are constructed to determine the activation energy and frequency factor, which are vital for optimizing reactions. 3 However, these methods are time-consuming because they require repeated sampling and quantification. Recently, efficient techniques using a continuous flow reactor and in-line measurement have been developed to determine reaction kinetics (Figure 1b).…”

SnCl2‐Catalyzed Acetalation/Selective Benzoylation Sequence for the Synthesis of Orthogonally Protected Glycosyl Acceptors

“…In particular, arylidene acetals have been widely used to protect the 4‐ and 6‐hydroxyl groups of glycosides due to their stability under non‐acid conditions [3d,4] . Furthermore, the 4,6‐arylidene acetals of glycosides can undergo a regioselective ring‐opening by different reagents and conditions to provide either a free OH at 4‐ or 6‐position, [4a–d] or a complete deprotection through acetal hydrolysis or hydrogenolysis [4e–h] . One‐pot strategies based on 4,6‐ O ‐arylidene acetalation and subsequent acylation were thus developed to synthesize fully protected products (Scheme 1b), [5] and orthogonally protected glycoside acceptors with a 4‐ or 6‐OH could be obtained efficiently after these products underwent regioselective ring‐opening.…”