2-Nitrobenzyl bromide
[CAS# 3958-60-9]

Identification

• Classification: Organic raw materials >> Aryl compounds
• Name: 2-Nitrobenzyl bromide
• Synonyms: alpha-Bromo-2-nitrotoluene
• Molecular Formula: C₇H₆BrNO₂
• Molecular Weight: 216.03
• CAS Registry Number: 3958-60-9
• EC Number: 223-558-9
• SMILES: C1=CC=C(C(=C1)CBr)[N+](=O)[O-]

Properties

• Density: 1.7±0.1 g/cm³ Calc.^*
• Melting point: 45 - 48 °C (Expl.)
• Boiling point: 275.2±15.0 °C 760 mmHg (Calc.)^*
• Flash point: 120.2±20.4 °C (Calc.)^*
• Index of refraction: 1.612 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05 Danger
• Risk Statements: H314
• Safety Statements: P260-P264-P280-P301+P330+P331-P302+P361+P354-P304+P340-P305+P354+P338-P316-P321-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Serious eye damage	Eye Dam.	1	H318

• Transport Information: UN 2811

Discovery and Applications

2-Nitrobenzyl bromide is an aromatic compound recognized for its utility in organic synthesis, particularly as an alkylating agent and a photolabile protecting group. The discovery and study of benzyl bromides and their derivatives, including 2-nitrobenzyl bromide, trace back to systematic research in aromatic halogen compounds during the late 19th and early 20th centuries. Early chemical investigations focused on understanding the reactivity imparted by the nitro group in combination with halomethyl substituents, revealing that the electron-withdrawing nature of the nitro group strongly influences the behavior of the molecule in substitution and photochemical reactions.

The synthesis of 2-nitrobenzyl bromide is typically achieved through the bromination of 2-nitrotoluene at the benzylic position. This transformation commonly employs N-bromosuccinimide (NBS) in the presence of a radical initiator like benzoyl peroxide or azobisisobutyronitrile (AIBN) under light or heat to facilitate radical bromination. The resulting compound features a bromomethyl group ortho to the nitro substituent on the benzene ring. This specific substitution pattern imparts distinct electronic characteristics, making 2-nitrobenzyl bromide a particularly reactive species in nucleophilic substitution reactions.

One of the most well-established applications of 2-nitrobenzyl bromide is its role in the formation of 2-nitrobenzyl-protected derivatives. In organic synthesis, 2-nitrobenzyl groups are used as photolabile protecting groups for functional groups such as alcohols, carboxylic acids, thiols, and amines. Upon exposure to ultraviolet light, the 2-nitrobenzyl group undergoes a photochemical reaction leading to the cleavage of the bond between the protecting group and the substrate, thereby releasing the free functional group. This property has been exploited in a variety of fields, including peptide synthesis, nucleic acid chemistry, and the design of photoresponsive materials.

In the realm of materials science, 2-nitrobenzyl derivatives are incorporated into polymers and surfaces that require light-triggered activation or degradation. For example, polymers functionalized with 2-nitrobenzyl groups can undergo cleavage upon UV irradiation, enabling applications in controlled drug delivery, photolithography, and the fabrication of smart materials. The precise control afforded by light exposure allows for spatial and temporal regulation of chemical reactions, a feature critical in modern material engineering and biomedical research.

2-Nitrobenzyl bromide has also been employed in the synthesis of biologically active molecules. The nitro group serves as a useful synthetic handle that can be chemically reduced to an amino group, allowing for subsequent derivatization into a variety of aromatic amine-containing compounds. Such transformations have relevance in the preparation of pharmaceutical intermediates, agrochemical agents, and specialty chemicals.

The compound's chemical reactivity is primarily characterized by its ability to act as a strong alkylating agent. The benzylic bromide group is highly susceptible to nucleophilic attack, and the electron-withdrawing nitro group further enhances the electrophilicity of the benzylic carbon. This makes 2-nitrobenzyl bromide particularly effective for reactions with soft nucleophiles, enabling the efficient formation of carbon-nitrogen, carbon-oxygen, and carbon-sulfur bonds.

Physical properties of 2-nitrobenzyl bromide include a pale yellow crystalline appearance and moderate solubility in organic solvents such as dichloromethane, acetone, and ethyl acetate. It typically exhibits a melting point suitable for handling under standard laboratory conditions. However, it is sensitive to moisture, and exposure to water can lead to hydrolysis of the bromomethyl group to form the corresponding benzyl alcohol derivative. Therefore, storage under anhydrous conditions in tightly sealed containers is recommended.

Safety considerations are crucial when working with 2-nitrobenzyl bromide. It is classified as a hazardous material, capable of causing skin, eye, and respiratory tract irritation. Proper protective equipment, including gloves, goggles, and lab coats, should be worn when handling the substance. Work involving 2-nitrobenzyl bromide should be conducted in a well-ventilated area or under a fume hood to prevent inhalation of vapors.

Overall, 2-nitrobenzyl bromide is a compound of considerable importance in modern organic and materials chemistry. Its well-documented applications as an alkylating agent and photolabile protecting group make it a vital tool for researchers seeking to develop new molecules, advanced materials, and light-controlled chemical systems.

References

1980. Nitrobenzyl halides and carbamates as prototype bioreductive alkylating agents. Journal of Medicinal Chemistry, 23(8).
DOI: 10.1021/jm00182a027

2016. Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process. Nature Communications, 7.
DOI: 10.1038/ncomms12933

2023. Synthesis and Evaluation of Herbicidal Activity of methanone Derivatives. Russian Journal of General Chemistry, 93(10).
DOI: 10.1134/s1070363223100122