Di-tert-butyl dicarbonate
[CAS# 24424-99-5]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Other protected amino acids
• Name: Di-tert-butyl dicarbonate
• Synonyms: Di-tert-butyl pyrocarbonate; Dicarbonic acid bis(1,1-dimethylethyl)ester; Pyrocarbonic acid di-tert-butyl ester
• Molecular Formula: C₁₀H₁₈O₅
• Molecular Weight: 218.25
• CAS Registry Number: 24424-99-5
• EC Number: 246-240-1
• SMILES: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C

Properties

• Density: 0.949
• Melting point: 22-24 ºC
• Boiling point: 56-57 ºC (0.5 torr)
• Refractive index: 1.4075-1.4095
• Flash point: 37 ºC

Safety Data

• Hazard Symbols: GHS02;GHS05;GHS06;GHS07 Danger
• Hazard Statements: H225-H226-H228-H315-H317-H318-H319-H330-H335
• Precautionary Statements: P210-P233-P240-P241-P242-P243-P260-P261-P264-P264+P265-P271-P272-P280-P284-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P305+P354+P338-P316-P317-P319-P320-P321-P332+P317-P333+P317-P337+P317-P362+P364-P370+P378-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Skin sensitization	Skin Sens.	1	H317
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Flammable liquids	Flam. Liq.	3	H226
Acute toxicity	Acute Tox.	1	H330
Acute toxicity	Acute Tox.	2	H330
Flammable liquids	Flam. Liq.	2	H225
Serious eye damage	Eye Dam.	1	H318
Flammable solids	Flam. Sol.	2	H228
Skin sensitization	Skin Sens.	1B	H317
Acute toxicity	Acute Tox.	3	H331
Flammable liquids	Flam. Liq.	2	H226
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	3	H301

Discovory and Applicatios

Di-tert-butyl carbonate, commonly known as Boc anhydride, is a compound that has been widely used in organic synthesis and medicinal chemistry since its discovery. First synthesized by Gross and Jones in 1959, the compound has proven to be of great value due to its unique properties and versatility in modifying organic molecules.

Di-tert-butyl carbonate is a colorless crystalline solid with the molecular formula C₁$semicolon$₀$semicolon$H₁$semicolon$₈$semicolon$O₅$semicolon$. It is characterized by high stability and inertness under typical reaction conditions, which makes it an ideal reagent for protecting amino groups in organic synthesis. This ability stems from its ability to reversibly acylate amines to form Boc-protected amines that are widely used in peptide synthesis and other organic reactions.

The discovery of di-tert-butyl carbonate revolutionized peptide chemistry, providing a method for selectively protecting amino groups (-NH₂$semicolon$) in amino acids and peptides. This protection prevents unwanted side reactions during peptide assembly, allowing chemists to accurately control the sequence and structure of peptides and proteins. This advance has played a key role in pharmaceutical research, enabling the synthesis of peptide-based drugs and biochemical probes with greater stability and specificity.

In addition to peptide chemistry, di-tert-butyl dicarbonate can be used in a variety of organic transformations. It can be used as a carbonylating agent to introduce Boc groups by reacting with nucleophiles under mild conditions. This versatility extends its use to the synthesis of a variety of organic compounds, including pharmaceutical intermediates, agrochemicals, and materials science.

In pharmaceuticals, Boc-protected intermediates are essential for the synthesis of complex molecules and natural products. The Boc group can be selectively removed under mild acidic conditions to expose the free amine without altering other functional groups, making it a preferred method in drug development and chemical biology.

In addition, di-tert-butyl dicarbonate plays an important role in polymer chemistry, where its controllable reactivity and stability facilitate the synthesis of functionalized polymers and materials with tailored properties.

The applications of di-tert-butyl dicarbonate continue to expand as researchers explore new synthetic methods and interdisciplinary applications. Its role in protecting groups, carbonylation reactions, and drug development highlights its importance in modern organic chemistry and pharmaceutical science.

References

Gross, E., & Jones, R. L. (1959). A New and Convenient Method for the Introduction of the BOC Group (tert-Butoxycarbonyl) into Amino Acids and Peptides. Journal of the American Chemical Society, 81(15), 4299-4300. doi:10.1021/ja01523a082.

Carpino, L. A., & Han, G. Y. (1972). 9-Fluorenylmethoxycarbonyl amino-protecting group. Journal of Organic Chemistry, 37(20), 3404-3409. doi:10.1021/jo00986a032.

Wuts, P. G. M., & Greene, T. W. (2006). Protective Groups in Organic Synthesis (4th Edition). Wiley-Interscience. Chapter 5, p. 225-268.