2-(2-(2-(2-Aminoethoxy)ethoxy)ethoxy)ethanol

This compound is typically encountered as a colorless to pale yellow viscous liquid with a faint amine-like odor. Its molecular formula is C8H19NO4, corresponding to a molecular weight of 193.24. The boiling point is approximately 130–135 °C at reduced pressure (0.5 mmHg), with a calculated density near 1.07 g/cm³ at 20 °C. It is completely miscible with water and polar organic solvents including methanol, ethanol, and dimethyl sulfoxide due to the hydrophilic polyether chain and terminal functional groups. The molecule contains a primary amine at one terminus and a primary alcohol at the other, connected by a triethylene glycol spacer. Both functional groups are capable of hydrogen bonding and chemical derivatization. The compound is hygroscopic and may absorb carbon dioxide from air to form carbamate salts. Storage in tightly sealed containers under inert atmosphere at reduced temperature (2–8 °C) is recommended to maintain purity. Contact with strong oxidizing agents, acid chlorides, and isocyanates should be avoided.

2(2(2(2Aminoethoxy)ethoxy)ethoxy)ethanol, also known as aminoPEG4alcohol, is a heterobifunctional polyethylene glycol derivative featuring a fourunit ethylene glycol chain terminated by a primary amine at one end and a primary alcohol at the other. This molecular architecture combines the hydrophilicity and flexibility of a PEG spacer with two orthogonal reactive handles for bioconjugation and materials chemistry. The ethylene glycol units impart water solubility, reduce nonspecific binding, and provide conformational freedom. The primary amine serves as a nucleophilic site for amide formation, reductive amination, or alkylation, while the alcohol enables esterification, etherification, or conversion to other functional groups such as halides or tosylates. The defined chain length of four ethylene glycol units provides optimal spacing for minimizing steric hindrance in conjugates while maintaining sufficient hydrophilicity. This combination of orthogonal functionality and a hydrophilic spacer makes the compound a versatile building block for constructing antibodydrug conjugates, targeted therapeutics, and functional materials where controlled spacing and water solubility are essential.

Bioconjugation and Linker Chemistry
This heterobifunctional PEG derivative is extensively employed as a linker in the preparation of antibodydrug conjugates, PROTACs, and other targeted therapeutics. The amine can be coupled to carboxylic acidcontaining drugs or targeting ligands via amide bond formation, while the alcohol enables attachment to antibodies or other biomolecules through esterification or activation as a leaving group. The PEG spacer improves aqueous solubility, reduces aggregation, and enhances pharmacokinetic properties of the resulting conjugates.

Surface Functionalization and Hydrogel Synthesis
The compound serves as a building block for modifying surfaces with hydrophilic, nonfouling coatings. The amine can anchor the molecule to activated surfaces such as NHSesters or epoxides, while the alcohol provides a handle for further functionalization or crosslinking. Incorporation into hydrogel networks yields materials with controlled swelling, biocompatibility, and mechanical properties for applications in tissue engineering and drug delivery.

Pharmaceutical Intermediate
In drug discovery, this aminoPEG alcohol is used to improve the solubility and pharmacokinetic profiles of hydrophobic drug candidates. Attachment via the amine or alcohol introduces a hydrophilic PEG chain that can reduce clearance rates and minimize offtarget interactions. The terminal alcohol can be further derivatized to introduce targeting moieties or imaging agents for theranostic applications.

Organic Synthesis Building Block
As a versatile synthetic intermediate, 2(2(2(2aminoethoxy)ethoxy)ethoxy)ethanol participates in diverse transformations including Nacylation, Oalkylation, and Mitsunobu reactions. The orthogonal reactivity of the two termini enables sequential functionalization: the amine can be protected while the alcohol is modified, followed by deprotection and further elaboration at the amine site. Its utility extends to the synthesis of dendritic structures, crown ether analogs, and functionalized PEGs for applications in catalysis, sensing, and drug delivery.