Chemical Identity and Structure

Triethylene glycol bis(chloroformate) is a symmetric bifunctional molecule built on a triethylene glycol (TEG, or PEG3) backbone. Each hydroxyl terminus of triethylene glycol is converted to a chloroformate group (–OCOCl), yielding two highly reactive acylating sites separated by a flexible, hydrophilic spacer of approximately 11 atoms. This architecture combines the reactivity of chloroformate chemistry with the water-compatibility and conformational flexibility characteristic of poly(ethylene glycol)-type linkers.

The compound belongs to the broader class of bis(chloroformate) reagents, which are valued in synthetic chemistry for introducing carbonate or carbamate bridges between two nucleophilic partners. The triethylene glycol spacer reduces steric strain and can improve aqueous solubility of conjugates relative to purely aliphatic crosslinkers.

Reactivity and Synthetic Applications

The chloroformate groups of triethylene glycol bis(chloroformate) react readily with nucleophiles under mild conditions. Reaction with primary or secondary alcohols yields carbonate linkages (–OCOO–), while reaction with primary or secondary amines produces carbamate (urethane) bonds (–OCONH–). Both reaction types proceed with liberation of hydrogen chloride (HCl), so the use of an appropriate base (e.g., triethylamine, pyridine, or sodium bicarbonate) is standard practice to neutralize the acid byproduct and drive the reaction forward.

Key synthetic applications include:

• Polymer and materials chemistry: Incorporation as a PEG-containing crosslinking unit in polycarbonate networks, hydrogels, and dendrimers, imparting hydrophilicity and tunable degradability.
• Bioconjugation: Coupling of biomolecules (e.g., peptides, saccharides, or drug candidates) via carbonate or carbamate bonds, leveraging the TEG spacer to reduce immunogenicity and improve pharmacokinetics.
• Small-molecule synthesis: Preparation of symmetric or asymmetric bis-carbonate intermediates for use in medicinal chemistry and prodrug design.
• Surface modification: Functionalization of hydroxyl- or amine-bearing surfaces with a PEG-type tether to modulate surface wettability and reduce nonspecific adsorption.

Handling, Safety, and Storage

Triethylene glycol bis(chloroformate) is a moisture-sensitive reagent. On exposure to atmospheric moisture or water, chloroformate groups hydrolyze rapidly, releasing hydrogen chloride gas and the corresponding carbonic acid species. Therefore, all manipulations should be performed under anhydrous conditions using dried glassware, inert-atmosphere techniques (nitrogen or argon), and dry solvents such as dichloromethane, tetrahydrofuran, or acetonitrile.

Personal protective equipment (PPE): Chemical-resistant gloves, safety goggles, and a laboratory coat are required. Work should be performed in a well-ventilated fume hood due to the potential generation of HCl vapor. In the event of skin or eye contact, flush immediately with copious water and seek medical attention.

Storage: Store in a tightly sealed container under an inert atmosphere, away from moisture, heat, and incompatible materials (strong bases, water, alcohols, amines). Refrigerated storage (2–8 °C) is typically recommended to maximize shelf life. Consult the product's Safety Data Sheet (SDS) and Certificate of Analysis (CoA) for lot-specific purity data and updated hazard information before use.

Quality, Purity, and Product Specification

Research-grade triethylene glycol bis(chloroformate) is supplied by Aladdin Scientific under SKU T347641. Researchers should verify purity by reviewing the Certificate of Analysis (CoA) provided with each lot. Typical analytical characterization methods include:

• NMR spectroscopy (¹H and ¹³C) to confirm structural identity and absence of hydrolysis products.
• GC or HPLC purity assay to quantify the main component against potential impurities.
• Titration or argentometric methods for active chlorine content, confirming intact chloroformate functionality.

Lot-to-lot consistency is critical for reproducible crosslinking or conjugation yields. Contact Aladdin Scientific technical support for custom quantities, bulk pricing, or additional analytical documentation.