Benzophenone Imine: Versatile Compound for Synthesizing Unnatural α-Amino Acids

General Description

Benzophenone imine is a clear liquid with unique properties, including a molecular weight of 181.23 g/mol, melting point of -30°C, and boiling point of 151-153℃. It is slightly soluble in DMSO and ethyl acetate but has low water solubility. The compound serves as a versatile platform for synthesizing unnatural α-amino acids, which are valuable building blocks for enhancing peptide function. By utilizing redox-active copper catalysts, efficient cross-coupling reactions can be achieved, enabling the creation of tetrasubstituted carbon centers. Benzophenone imine also allows for the production of dehydroalanine derivatives through successive β-functionalization and oxidation. Safety precautions should be taken when handling this compound, as it can cause skin and eye irritation, as well as respiratory discomfort if inhaled.

Figure 1. Benzophenone imine

Physical and Chemical Properties

Benzophenone imine is a clear colorless to light yellow-brownish liquid. It has a molecular weight of 181.23 g/mol and a melting point of -30°C. The boiling point of benzophenone imine is 151-153℃ (1.33kPa), with a relative density of 1.080 and refractive index of 1.6169. It is slightly soluble in DMSO and ethyl acetate, with a water solubility of 0.3g/L at 25ºC. The compound has a pKa value of 6.82 (25°C) and is stable when stored under inert atmosphere at room temperature. Computed properties of benzophenone imine include XLogP3 of 3, one hydrogen bond donor count, one hydrogen bond acceptor count, two rotatable bond counts, an exact mass of 181.089149355 g/mol, and a monoisotopic mass of 181.089149355 g/mol. The topological polar surface area of benzophenone imine is 23.8Ų. Benzophenone imine is commonly used as an intermediate in the production of pharmaceuticals, agrochemicals, and organic compounds. Its unique properties make it a useful component in various applications. ¹

Applications in Unnatural α-Amino Acid Synthesis

Benzophenone imine has found important applications in synthetic organic chemistry as a platform for the synthesis of highly congested unnatural α-amino acids. These unnatural α-amino acids are valuable building blocks for upgrading the function of peptides. The catalytic activation of amino acid Schiff bases using redox-active copper catalysts enables efficient cross-coupling to construct contiguous tetrasubstituted carbon centers. This method is mild and broad functional group compatibility is achieved. Moreover, successive β-functionalization and oxidation of amino acid Schiff bases can afford dehydroalanine derivatives bearing tetrasubstituted carbon, and a three-component cross-coupling reaction has shown high utility. Diastereoselective reactions have also been achieved using menthol derivatives as a chiral auxiliary, delivering enantiomerically enriched α-amino acids bearing α,β-continuous tetrasubstituted carbon. The synthesized highly congested unnatural α-amino acids can be derivatized and incorporated into peptide synthesis, upgrading their functionality. Therefore, Benzophenone imine serves as a versatile platform for the synthesis of unnatural α-amino acids with potential applications in the pharmaceutical industry and chemical biology. ²

Safety Considerations

Benzophenone imine is a chemical compound that requires careful handling due to its potential safety hazards. This compound has been identified to cause skin irritation upon contact, meaning it can lead to redness, itching, and inflammation of the skin. Therefore, it is crucial to avoid direct skin exposure and to use appropriate personal protective equipment, such as gloves and lab coats, when working with this substance. Additionally, Benzophenone imine has the potential to cause serious eye irritation. In case of contact with the eyes, it may result in pain, redness, and possible damage to the cornea. To prevent eye exposure, safety goggles or a face shield should be worn at all times when handling this compound. Furthermore, Benzophenone imine may also cause respiratory irritation if inhaled. It is important to work in a well-ventilated area or use appropriate engineering controls, such as fume hoods, to minimize exposure. If respiratory irritation occurs, it is recommended to move to a fresh air environment and seek medical attention if symptoms persist. In summary, Benzophenone imine should be handled with caution to avoid skin and eye irritation, as well as respiratory discomfort. Proper safety measures, including the use of personal protective equipment and adequate ventilation, should be followed when working with this chemical compound to ensure a safe working environment. ³

Reference

1. Benzophenone imine. National Center for Biotechnology Information, 2023, PubChem Compound Summary for CID 136809.

2. Matsumoto Y, Sawamura J, Murata Y, Nishikata T, Yazaki R, Ohshima T. Amino Acid Schiff Base Bearing Benzophenone Imine As a Platform for Highly Congested Unnatural α-Amino Acid Synthesis. J Am Chem Soc. 2020 May 6;142(18):8498-8505.

3. Benzophenone imine. European Chemicals Agency, EC / List no. 600-205-0.