(1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol
[CAS# 1351997-21-1]

Identification

• Classification: Organic raw materials >> Alcohols, phenols, phenolic compounds and derivatives
• Name: (1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol
• Molecular Formula: C₁₀H₁₃NO
• Molecular Weight: 163.22
• CAS Registry Number: 1351997-21-1
• SMILES: C1C[C@@H](C2=CC=CC=C2[C@H]1N)O

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 320.3±37.0 ºC 760 mmHg (Calc.)^*
• Flash point: 147.5±26.5 ºC (Calc.)^*
• Index of refraction: 1.6 (Calc.)^*

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

Discovory and Applicatios

(1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol is a chiral bicyclic compound in which a tetrahydronaphthalene core is substituted with an amino group at the fourth carbon and a hydroxyl group at the first carbon. The stereochemistry of the molecule, with both the 1- and 4-positions in the S-configuration, plays a critical role in its chemical reactivity and potential interactions with biological targets. The combination of a secondary alcohol and a primary amine on a partially saturated aromatic system provides multiple reactive sites, making this compound a useful intermediate in the synthesis of biologically active molecules and complex heterocycles.

The synthesis of (1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol typically involves stereoselective reduction of 1,2,3,4-tetrahydronaphthalen-1-one derivatives followed by amination at the 4-position using suitable protecting group strategies to maintain stereochemical integrity. The chiral centers are introduced or preserved using asymmetric synthesis techniques or chiral starting materials, and reaction conditions are carefully controlled to prevent racemization. The resulting product is generally isolated as a crystalline solid, with purification accomplished through recrystallization or chromatographic methods.

In synthetic organic chemistry, the compound serves as a versatile intermediate for the construction of substituted tetrahydronaphthalene derivatives. The hydroxyl group can participate in esterification, etherification, or oxidation reactions, while the amino group can undergo acylation, alkylation, or formation of heterocyclic rings. These functionalities allow selective derivatization and enable the preparation of molecules with tailored chemical and biological properties. The stereochemical configuration provides additional control over the spatial orientation of substituents, which is critical for designing chiral ligands, inhibitors, or other bioactive molecules.

In medicinal chemistry, derivatives of (1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol have been investigated as potential scaffolds for central nervous system agents, enzyme inhibitors, or receptor modulators. The bicyclic core provides rigidity and planarity, allowing favorable interactions with protein binding sites, while the amino and hydroxyl groups facilitate hydrogen bonding and other non-covalent interactions. Modifying the substituents at these positions enables tuning of pharmacokinetic and pharmacodynamic properties, supporting structure–activity relationship studies and optimization of lead compounds.

The compound is also relevant in chemical methodology research. Its combination of a secondary alcohol and primary amine on a chiral bicyclic scaffold allows exploration of stereoselective reactions, protective group strategies, and cross-coupling chemistry. It can serve as a model substrate for studying reactivity patterns in chiral amines and alcohols, providing insight into regioselectivity, stereochemistry, and reaction optimization in heterocyclic and asymmetric synthesis.

Physically, (1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol is generally obtained as a solid with moderate solubility in polar organic solvents and limited solubility in water. It is stable under standard laboratory conditions but should be stored protected from strong acids, bases, and oxidizing agents to maintain both the stereochemistry and functional group integrity. Proper storage ensures that the compound remains suitable for synthetic transformations and biological investigations.

Overall, (1S,4S)-4-amino-1,2,3,4-tetrahydronaphthalen-1-ol is a chiral bicyclic intermediate with dual functional groups that enable selective chemical transformations and derivatization. Its stereochemistry, amino, and hydroxyl functionalities make it a versatile building block for the synthesis of bioactive compounds, heterocyclic derivatives, and chiral ligands in medicinal and synthetic organic chemistry.

References

2018. Kinase inhibitors. US Patent, 9994565.

2017. Benzimidazolyl-methyl urea derivatives as alx receptor agonists. EP Patent, 3030560.

2015. Derivatives of 4-hydroxy-1,2,3,4-tetrahydronaphtalen-1-yl urea and their use in the treatment of, inter alia, diseases of the respiratory tract. EP Patent, 2788345.