Bis(4-tetrahydropyranyl)amine: Properties, Synthesis & Uses
Bis(4-tetrahydropyranyl)amine: Properties, Synthesis & Uses
Bis(4-tetrahydropyranyl)amine is a secondary cyclic amine reagent featuring two tetrahydropyran-4-yl substituents on nitrogen, making it a versatile building block for organic synthesis and medicinal chemistry applications.
- Chemical Name
- Bis(4-tetrahydropyranyl)amine
- SKU
- B731737
- Compound Class
- Secondary aliphatic amine; cyclic ether-containing amine
- Functional Group
- Secondary amine (N–H) flanked by two THP rings
- Key Application
- Synthetic building block in organic and medicinal chemistry
- Supplier
- Aladdin Scientific
Chemical Identity and Structure
Bis(4-tetrahydropyranyl)amine consists of a secondary amine nitrogen bearing two tetrahydropyran-4-yl (THP-4-yl) groups. The tetrahydropyranyl rings are six-membered oxygen-containing saturated heterocycles, and their attachment at the 4-position places the nitrogen at a sterically accessible equatorial-like environment. This architecture combines the nucleophilicity of a secondary amine with the conformational rigidity and polarity imparted by the two THP rings.
The compound is classified as a saturated, aliphatic secondary amine. The presence of two ether oxygens within the THP rings enhances aqueous solubility relative to purely carbocyclic analogues, an important property for biological assay compatibility and green-chemistry applications.
Synthesis and Preparation
Secondary amines of this type are generally accessible via reductive amination, where tetrahydropyran-4-one (THP-4-one) is reacted with tetrahydropyran-4-amine under reducing conditions, typically employing sodium cyanoborohydride or sodium triacetoxyborohydride as the hydride source. Alternatively, direct N-alkylation of tetrahydropyran-4-amine with a suitable electrophilic THP-4 precursor can provide the target compound.
Catalytic hydrogenation approaches using palladium on carbon or Raney nickel under hydrogen atmosphere represent additional routes applicable to appropriately substituted precursors. The choice of synthetic route influences the stereochemical outcome and purity profile of the final material; Aladdin Scientific supplies Bis(4-tetrahydropyranyl)amine (SKU B731737) as a ready-to-use reagent, eliminating the need for in-house preparation.
Research Applications
Bis(4-tetrahydropyranyl)amine serves primarily as a building block in organic synthesis and drug discovery programs. As a secondary amine, it can participate in a broad range of transformations including acylation to form amides, sulfonylation to form sulfonamides, reductive amination, and coupling reactions with carbonyl electrophiles.
In medicinal chemistry, THP-containing amines are valued for their ability to improve the physicochemical profile of drug candidates, including increased aqueous solubility, improved metabolic stability compared to open-chain analogues, and reduced lipophilicity (lower logP). These features align with modern drug design criteria aimed at optimizing ADMET properties. Bis(4-tetrahydropyranyl)amine can also serve as a ligand component in coordination chemistry or as a chiral-auxiliary precursor when enantiopure forms are employed.
Handling, Storage, and Safety Considerations
As a secondary aliphatic amine, Bis(4-tetrahydropyranyl)amine should be handled with standard laboratory precautions appropriate for amine-class reagents. Personal protective equipment including nitrile gloves, safety glasses, and a laboratory coat is recommended. Work in a well-ventilated fume hood to minimize inhalation exposure.
Storage under cool, dry, and dark conditions in a tightly sealed container is advisable to prevent moisture uptake and oxidative degradation. Specific storage temperature recommendations and shelf-life data should be confirmed from the product's Safety Data Sheet (SDS) provided by Aladdin Scientific. Researchers should consult the current SDS for complete hazard classification, first-aid measures, and disposal guidance prior to use.
Frequently asked questions
What is Bis(4-tetrahydropyranyl)amine used for in research?
Bis(4-tetrahydropyranyl)amine is primarily used as a secondary amine building block in organic synthesis and medicinal chemistry. It can undergo acylation, sulfonylation, reductive amination, and related transformations to introduce a bis-THP amine motif into target molecules, often with the goal of improving aqueous solubility and metabolic stability of drug candidates.
How should Bis(4-tetrahydropyranyl)amine be stored?
The compound should be stored in a tightly sealed container under cool, dry, and dark conditions to prevent moisture absorption and degradation. For precise storage temperature and shelf-life information, consult the Safety Data Sheet (SDS) available from Aladdin Scientific for SKU B731737.
What are the advantages of using THP-containing amines in drug discovery?
Tetrahydropyranyl-containing amines offer improved aqueous solubility relative to carbocyclic or purely aliphatic analogues due to the presence of a ring oxygen, and they typically display lower lipophilicity (logP) and enhanced metabolic stability. These physicochemical advantages support better ADMET profiles in drug candidates, making THP-based building blocks attractive in lead optimization programs.
Can Bis(4-tetrahydropyranyl)amine be used in amide bond formation?
Yes, as a secondary amine it can react with activated carboxylic acid derivatives such as acid chlorides or NHS esters, as well as via standard peptide coupling conditions using reagents like HATU or EDC, to form the corresponding tertiary amide products. Steric considerations from the two THP rings should be evaluated for each specific substrate.
References
- March, J.; Smith, M. B. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed.; Wiley: Hoboken, NJ, 2013. (General reference for secondary amine reactivity and reductive amination)
- Meanwell, N. A. Improving Drug Candidates by Design: A Focus on Physicochemical Properties as a Means of Improving Compound Disposition and Safety. Chem. Res. Toxicol. 2011, 24, 1420–1456. (Background on THP and cyclic ethers in medicinal chemistry ADMET optimization) doi:10.1021/tx200211v
- Aladdin Scientific. Product Page: Bis(4-tetrahydropyranyl)amine, SKU B731737. Aladdin Scientific, Shanghai. (Primary product source)
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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