1,2:3,4-Di-O-isopropylidene-D-galactopyranose
[CAS# 4064-06-6]

Identification

• Classification: Biochemical >> Carbohydrate >> Monosaccharide
• Name: 1,2:3,4-Di-O-isopropylidene-D-galactopyranose
• Synonyms: [(1S,2R,6R,8R,9S)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.02,6]dodecan-8-yl]methanol
• Molecular Formula: C₁₂H₂₀O₆
• Molecular Weight: 260.29
• CAS Registry Number: 4064-06-6
• EC Number: 223-771-7
• SMILES: CC1(O[C@H]2[C@H](O[C@H]3[C@@H]([C@H]2O1)OC(O3)(C)C)CO)C

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 120 - 122 ºC (Expl.), 120 - 122 ºC (Expl.)
• Boiling point: 366.8 ºC 760 mmHg (Calc.)^*, 499.5 ºC (Expl.)
• Flash point: 159.3±26.5 ºC (Calc.)^*
• Index of refraction: 1.456 (Calc.)^*, 1.466 (Expl.)
• Alpha: -57.5 º (c=3, CHCl3) (Expl.)

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

1,2:3,4-Di-O-isopropylidene-D-galactopyranose is a doubly protected derivative of D-galactose in which two pairs of vicinal hydroxyl groups are converted into isopropylidene acetals. D-galactose was identified in the nineteenth century as a constituent of lactose and was subsequently recognized as an aldohexose closely related to D-glucose. The pyranose ring structure of D-galactose, together with its stereochemical configuration, was established through extensive classical studies involving oxidation, reduction, and derivative formation. As carbohydrate chemistry advanced in the twentieth century, the need for selective protection of hydroxyl groups led to the development of acetal-based protecting strategies.

The formation of isopropylidene derivatives of sugars became widely adopted after it was demonstrated that acetone, in the presence of an acid catalyst, reacts with vicinal diols to form cyclic acetals. These protecting groups, commonly referred to as acetonides, provide stability under neutral and basic conditions while being removable under controlled acidic treatment. In 1,2:3,4-di-O-isopropylidene-D-galactopyranose, the hydroxyl groups at positions 1 and 2 form one isopropylidene acetal, and those at positions 3 and 4 form a second. This double protection leaves the remaining hydroxyl group, typically at position 6, available for selective modification.

The introduction of di-O-isopropylidene protection represented an important methodological advance in carbohydrate synthesis. By masking two adjacent diol systems, chemists could control reactivity patterns within the molecule and direct transformations to specific sites. Experimental studies demonstrated that such protected sugars exhibit reduced intermolecular hydrogen bonding and increased solubility in organic solvents compared with the parent monosaccharides. These properties facilitated purification, crystallization, and subsequent synthetic steps.

1,2:3,4-Di-O-isopropylidene-D-galactopyranose has been used as an intermediate in the preparation of selectively substituted galactose derivatives. Because the primary hydroxyl group at C-6 remains unprotected, it can undergo reactions such as esterification, ether formation, or oxidation without interference from the protected secondary hydroxyl groups. After the desired modification is achieved, the isopropylidene groups can be removed under acidic conditions to regenerate the free diol functionalities. This sequence allows stepwise construction of more complex carbohydrate structures.

The broader application of diacetonide sugars has been documented in the synthesis of glycosides, oligosaccharides, and carbohydrate-based building blocks. Protecting group strategies based on isopropylidene formation have also been employed in studies of reaction mechanisms, where controlled exposure of specific hydroxyl groups is required. The predictable stability and deprotection behavior of acetonides contributed to the establishment of systematic synthetic routes in glycochemistry.

In addition to synthetic utility, di-O-isopropylidene derivatives have been valuable in structural and conformational investigations. Crystalline protected sugars often provide well-defined samples suitable for physical measurements, and comparisons between protected and unprotected forms have informed understanding of ring conformation and intramolecular interactions. Such experimentally grounded observations have reinforced the structural models developed for hexopyranoses.

Although 1,2:3,4-di-O-isopropylidene-D-galactopyranose is not typically encountered outside research and specialized chemical production, its preparation and use reflect the documented evolution of carbohydrate protection chemistry. The compound exemplifies how acetonide formation enabled selective functionalization and advanced the synthesis of structurally defined sugar derivatives. Its role as an intermediate in controlled transformations underscores the importance of protecting group methodology in the experimentally established development of modern carbohydrate chemistry.

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