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

• Published in: Journal of organic chemistry 2020-12, Vol.85 (24), p.15849-15856
• Main Authors: Maki, Yuta, Nomura, Kota, Okamoto, Ryo, Izumi, Masayuki, Mizutani, Yasuhisa, Kajihara, Yasuhiro
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.0c00395

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.