2-Fluoro-5-nitrotoluene
[CAS 455-88-9]

Identification

• Classification: Chemical reagent >> Organic reagent >> Nitro compound
• Name: 2-Fluoro-5-nitrotoluene
• Synonyms: 1-Fluoro-2-methyl-4-nitrobenzene
• Molecular Formula: C₇H₆FNO₂
• Molecular Weight: 155.13
• CAS Registry Number: 455-88-9
• EC Number: 207-251-7
• SMILES: CC1=C(C=CC(=C1)[N+](=O)[O-])F

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Melting point: 38 - 40 °C (Expl.)
• Boiling point: 223.0 °C 760 mmHg (Calc.)^*, 241.2 - 242.6 °C (Expl.)
• Flash point: 105.0 °C (Calc.)^*, 105 °C (Expl.)
• Index of refraction: 1.53 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H312-H315-H319-H332-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H312
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

chemBlink Chemical Story

2-Fluoro-5-nitrotoluene is a substituted aromatic compound that serves as an important intermediate in pharmaceutical, agrochemical, and fine chemical synthesis. Although it is rarely encountered outside chemical manufacturing, it represents one of the most significant developments in modern organic chemistry: the strategic use of halogenated aromatic building blocks to construct increasingly sophisticated functional molecules. Its importance lies not in its own applications, but in the way its carefully arranged substituents enable efficient and selective chemical transformations.

The history of substituted aromatic compounds dates back to the rapid expansion of synthetic organic chemistry during the nineteenth century. As chemists learned to introduce nitro, halogen, alkyl, and other substituents onto benzene rings, they discovered that the position of each group profoundly influenced chemical reactivity. By the middle of the twentieth century, aromatic substitution patterns had become an essential design principle in synthetic chemistry, allowing researchers to predict reaction pathways and prepare increasingly complex molecules with remarkable precision.

Among these substituents, fluorine occupies a unique position. Although similar in size to hydrogen, fluorine is the most electronegative element, enabling it to modify molecular properties without dramatically changing molecular shape. During the past several decades, fluorine chemistry has transformed medicinal chemistry because fluorine can improve metabolic stability, alter lipophilicity, influence electronic distribution, and enhance binding interactions with biological targets. Today, fluorinated aromatic rings are found in a substantial proportion of modern pharmaceuticals and crop protection agents.

The nitro group contributes another dimension of synthetic versatility. Rather than serving merely as a functional group, it acts as one of the most useful synthetic handles in aromatic chemistry. Nitro groups can be selectively reduced to aromatic amines, which in turn become key intermediates for preparing amides, heterocycles, azo compounds, dyes, and numerous biologically active molecules. Consequently, nitro aromatics have remained indispensable starting materials throughout the development of synthetic chemistry.

2-Fluoro-5-nitrotoluene combines these two powerful design elements within a single molecule. The fluorine atom influences both electronic properties and substitution selectivity, while the nitro group provides a readily transformable functional group for further synthesis. The methyl substituent adds additional opportunities for side-chain functionalization through oxidation, halogenation, or carbon-carbon bond-forming reactions. Together, these substituents make the compound an exceptionally versatile intermediate capable of participating in many synthetic sequences.

Such fluoronitro aromatic compounds are widely employed in the preparation of pharmaceutical intermediates, agrochemical active ingredients, specialty dyes, pigments, and advanced heterocyclic compounds. They are especially valuable in medicinal chemistry, where precise substitution patterns often determine biological activity. Rather than introducing substituents individually during later synthetic stages, chemists frequently begin with carefully designed aromatic building blocks that already contain the desired substitution pattern, simplifying synthesis and improving overall efficiency.

The broader significance of compounds such as 2-fluoro-5-nitrotoluene reflects an important evolution in synthetic strategy. Modern organic chemistry increasingly relies on molecular design at the building-block level. Instead of constructing complex molecules atom by atom, chemists assemble them from multifunctional intermediates whose substitution patterns have already been optimized. This modular approach has accelerated the discovery of pharmaceuticals, crop protection agents, electronic materials, and functional organic molecules.

The scientific importance of 2-fluoro-5-nitrotoluene therefore extends beyond its identity as a substituted aromatic compound. It represents the philosophy of modern synthetic chemistry, in which carefully designed molecular building blocks enable efficient access to increasingly complex chemical space. Its continued use demonstrates how thoughtful molecular architecture at the earliest stages of synthesis can influence the success of entire research and manufacturing programs.

References

1. O'Hagan, D. (2008). "Understanding Organofluorine Chemistry: An Introduction to the C–F Bond." Chemical Society Reviews, 37, 308–319. https://doi.org/10.1039/B711844A

2. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, Part B: Reactions and Synthesis. 5th ed. Springer, 2007.

3. Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. (2008). "Fluorine in Medicinal Chemistry." Chemical Society Reviews, 37, 320–330. https://doi.org/10.1039/B610213C