tert-Butyl N-hydroxycarbamate
[CAS# 36016-38-3]

Identification

• Classification: Chemical reagent >> Organic reagent >> Ester >> Butyl ester compound
• Name: tert-Butyl N-hydroxycarbamate
• Synonyms: N-Boc-hydroxylamine
• Molecular Formula: C₅H₁₁NO₃
• Molecular Weight: 133.15
• CAS Registry Number: 36016-38-3
• EC Number: 252-836-2
• SMILES: CC(C)(C)OC(=O)NO

Properties

• Melting point: 53-57 °C

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H317-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P272-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P333+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2A	H319
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

tert-Butyl N-hydroxycarbamate, also known as Boc-NHOH, was first synthesized during investigations into protecting amine groups in organic synthesis. Chemists sought to develop stable protecting groups that could be easily removed under mild conditions to allow for selective functionalization of amines. The synthesis involved the reaction of tert-butylamine with chloroformates and hydroxylamine to form the N-hydroxycarbamate derivative. This discovery represented a significant advancement in organic chemistry, providing a versatile tool for selectively protecting amino groups in complex molecules.

tert-Butyl N-hydroxycarbamate is used as a protecting group for amines in organic synthesis, preventing unwanted reactions with other reagents while allowing desired transformations elsewhere in the molecule. This strategy is crucial in multi-step synthesis to control regioselectivity and achieve complex molecular architectures. After desired transformations, tert-Butyl N-hydroxycarbamate can be selectively removed under mild conditions to regenerate the free amine group, enabling the recovery of the original functionality without affecting other sensitive groups present.

tert-Butyl N-hydroxycarbamate is used in solid-phase peptide synthesis to protect the N-terminus of growing peptide chains, enabling efficient and high-yield synthesis of peptides and peptidomimetics for pharmaceutical research. It serves as part of orthogonal protecting group strategies in peptide synthesis, allowing precise control over peptide assembly for the synthesis of complex peptide structures with specific functionalities.

tert-Butyl N-hydroxycarbamate plays a crucial role in synthesizing pharmaceutical intermediates and active pharmaceutical ingredients (APIs), contributing to the development of new drug candidates with improved properties. It can be incorporated into prodrugs to improve drug stability, bioavailability, and tissue targeting, making it valuable in drug delivery systems.

In materials science, tert-Butyl N-hydroxycarbamate is used to modify surfaces and polymers, enhancing properties such as adhesion, corrosion resistance, and biocompatibility in coatings, adhesives, and biomedical devices. It is employed in polymer chemistry for controlled modification of polymer chains, allowing tailored properties such as solubility, thermal stability, and mechanical strength, expanding applications in drug delivery and nanotechnology.

References

2019. Hydroxylamine Derivatives in Synthesis. Organic & Biomolecular Chemistry, 17(28).
DOI: 10.1039/C9OB00987A