3-O-Benzyl-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose
[CAS# 18685-18-2]

Identification

• Classification: Biochemical >> Carbohydrate >> Monosaccharide
• Name: 3-O-Benzyl-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose
• Synonyms: NSC 56267
• Molecular Formula: C₁₉H₂₆O₆
• Molecular Weight: 350.41
• CAS Registry Number: 18685-18-2
• SMILES: CC1(OCC(O1)C2C(C3C(O2)OC(O3)(C)C)OCC4=CC=CC=C4)C

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 422.6±45.0 ºC 760 mmHg (Calc.)^*
• Flash point: 168.3±28.6 ºC (Calc.)^*
• Index of refraction: 1.548 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Discovory and Applicatios

3-O-Benzyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose is a selectively protected derivative of D-glucose in which the sugar is present in the furanose form. In this compound, two isopropylidene groups protect the 1,2- and 5,6-diols as cyclic acetals, and the hydroxyl group at the 3-position is converted into a benzyl ether. The molecule represents a typical example of multistep protecting group strategy in carbohydrate chemistry, developed to enable controlled and regioselective functionalization of monosaccharides.

The systematic use of protecting groups in sugar chemistry expanded significantly during the early and mid-20th century, following the establishment of carbohydrate stereochemistry. Chemists recognized that the presence of multiple hydroxyl groups in glucose required selective masking to allow predictable transformations. Treatment of D-glucose with acetone under acidic conditions was found to yield di-O-isopropylidene derivatives, particularly the 1,2:5,6-di-O-isopropylidene compound, which stabilizes the furanose ring and blocks four hydroxyl groups simultaneously. Structural confirmation of these acetonide derivatives was achieved through optical rotation measurements and later by infrared and nuclear magnetic resonance spectroscopy.

The introduction of a benzyl protecting group at the 3-position typically proceeds by reaction of the partially protected sugar with benzyl halides in the presence of base. The benzyl ether is stable under a wide range of neutral and basic conditions and can be removed selectively by catalytic hydrogenation. This orthogonality between acetonide and benzyl protecting groups became an important principle in synthetic design. The combination of two isopropylidene acetals and one benzyl ether allows the chemist to differentiate among hydroxyl positions and to introduce further modifications at specific sites after selective deprotection.

3-O-Benzyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose has been used as an intermediate in the synthesis of complex carbohydrates, glycosides, and natural product analogues. By protecting the 1,2- and 5,6-positions, the molecule leaves the 3- and 4-positions accessible in a controlled manner before benzylation, and subsequent manipulations can target remaining functional groups with high regioselectivity. Such strategies have been widely documented in carbohydrate synthesis, particularly in the preparation of rare sugars and stereochemically defined building blocks.

The presence of the two cyclic acetals influences the conformational preferences of the furanose ring. X-ray crystallographic studies of related diacetonide glucose derivatives have shown that the isopropylidene groups impose steric constraints that affect ring puckering and torsion angles. The benzyl substituent further modifies steric and electronic properties, which can influence reactivity in downstream transformations. Spectroscopic characterization, including proton and carbon nuclear magnetic resonance, confirms substitution patterns and anomeric configuration, with data consistent with the alpha orientation at the anomeric center.

Compounds of this type illustrate the methodological evolution of carbohydrate chemistry from structural elucidation to complex synthesis. The use of acetonide protection allows reversible masking of vicinal diols, while benzyl protection provides stability during subsequent reactions and can be removed under mild hydrogenolysis conditions. This combination supports multistep synthetic sequences without compromising the stereochemical integrity of the sugar framework.

In addition to synthetic applications, such protected derivatives have served as model compounds in studies of reaction mechanisms and protecting group stability. Controlled hydrolysis experiments have documented the relative rates of acetonide cleavage under acidic conditions, while hydrogenation studies have established reliable conditions for benzyl group removal without disturbing other functional groups.

3-O-Benzyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose therefore represents a well-characterized intermediate in carbohydrate synthesis. Its preparation, structural verification, and practical use are grounded in established experimental procedures that have contributed to the broader development of selective functional group manipulation in organic chemistry.

References

1979. Arzneimittel-Forschung. Drug Research., 29(986).
PMID: 315233