2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate
[CAS# 148893-10-1]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Other protected amino acids
• Name: 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate
• Synonyms: o-(7-Azabenzotriazol-1-yl)-N,N,N',N'-te-tramethyluronium hexafluorophosphate; HATU
• Molecular Formula: C₁₀H₁₅F₆N₆OP
• Molecular Weight: 380.23
• CAS Registry Number: 148893-10-1
• EC Number: 604-662-7
• SMILES: CN(C)C(=[N+](C)C)N1C2=C(N=CC=C2)[N+](=N1)[O-].F[P-](F)(F)(F)(F)F

Properties

• Melting point: 183-185 ºC

Safety Data

• Hazard Symbols: GHS02;GHS07 Danger
• Hazard Statements: H228-H315-H319-H335
• Precautionary Statements: P210-P264-P271-P240-P261-P280-P305+P351+P338-P302+P352-P304+P340-P312-P362-P370+P378-P403+P233-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin sensitization	Skin Sens.	1	H317
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Flammable solids	Flam. Sol.	1	H228
Eye irritation	Eye Irrit.	2A	H319
Respiratory sensitization	Resp. Sens.	1	H334
Acute toxicity	Acute Tox.	4	H302

Discovory and Applicatios

2-(7-Aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, commonly known as HATU, is a highly efficient coupling reagent that is widely used in peptide synthesis. Its development significantly improved the efficiency and reliability of peptide bond formation, making it a staple in synthetic organic chemistry.

HATU was developed in the late 20th century as part of a series of urea- and phosphorus-based coupling reagents. These reagents were designed to promote the formation of amide bonds, which are essential in the synthesis of peptides and proteins. HATU was developed to overcome the limitations of earlier reagents, such as low reactivity and side reactions. It combines the high reactivity of the tetramethylurea group with the stabilizing effect of the hexafluorophosphate counterion to form a reagent with excellent efficiency and low racemization.

HATU has the molecular formula C₉H₁₆F₆N₅OP and appears as a white to off-white crystalline powder. Its structure features a tetramethylurea core attached to an azabenzotriazole moiety, which enhances its reactivity. The hexafluorophosphate counterion further stabilizes the compound and increases its solubility in organic solvents.

The primary application of HATU is in peptide synthesis, where it is used as a coupling reagent to form peptide bonds between amino acids. It is particularly valued for its ability to effectively activate carboxyl groups, thereby promoting the formation of amide bonds under mild conditions. The use of HATU minimizes the risk of racemization, a common problem in peptide synthesis that results in the formation of unwanted stereoisomers.

In a typical peptide synthesis process, HATU is added to a solution containing the carboxyl group of one amino acid and the amine group of another. The reagent activates the carboxyl group, forming an intermediate that reacts with the amine to form the peptide bond. The process is efficient and produces high-purity peptides, making HATU a preferred choice in research and industrial applications.

HATU offers several advantages over traditional coupling reagents: it provides fast and efficient couplings, shortening reaction times; the risk of racemization is minimized, ensuring the synthesis of peptides with the correct stereochemistry; and HATU is compatible with a wide range of amino acids and protecting groups, making it suitable for complex peptide syntheses.

In addition to peptide synthesis, HATU is also used in the synthesis of amides, esters, and other organic compounds. Its high reactivity and mild reaction conditions make it suitable for a variety of applications in medicinal chemistry and material science.

HATU should be handled with care as it can irritate the skin, eyes, and respiratory system. Protective equipment such as gloves and goggles should be worn when handling the reagent. It should be stored in a cool, dry place away from moisture and incompatible materials.