5-(tert-Butyl)-2-chloropyridine
[CAS# 102236-19-1]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Chloropyridine
• Name: 5-(tert-Butyl)-2-chloropyridine
• Molecular Formula: C₉H₁₂ClN
• Molecular Weight: 169.65
• CAS Registry Number: 102236-19-1
• EC Number: 863-765-7
• SMILES: CC(C)(C)C1=CN=C(C=C1)Cl

Properties

• Density: 1.1±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.502, Calc.^*
• Boiling Point: 223.1±20.0 ºC (760 mmHg), Calc.^*
• Flash Point: 110.0±7.4 ºC, Calc.^*

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

Safety Data

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

Hazard Classification

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

Discovory and Applicatios

5-(tert-Butyl)-2-chloropyridine is a significant heterocyclic compound in the field of organic chemistry. Structurally, it consists of a pyridine ring with a tert-butyl group at the 5-position and a chlorine atom at the 2-position. This substitution pattern imparts the molecule with unique electronic and steric properties that make it a valuable intermediate for various applications, particularly in pharmaceutical synthesis, agrochemicals, and material science.

The discovery and development of 5-(tert-butyl)-2-chloropyridine are linked to the broader study of functionalized pyridine derivatives. Pyridines are one of the most versatile classes of heterocyclic compounds, known for their importance in medicinal chemistry due to their presence in many bioactive molecules. The introduction of a tert-butyl group at the 5-position enhances the compound’s stability by providing steric hindrance, while the chlorine atom at the 2-position serves as a reactive site for further chemical transformations.

In pharmaceutical chemistry, 5-(tert-butyl)-2-chloropyridine serves as a valuable intermediate in the synthesis of a wide range of biologically active molecules. The combination of the electron-withdrawing chlorine and the bulky tert-butyl group can influence the reactivity and pharmacokinetic properties of resulting compounds. This intermediate has been used in the preparation of antihypertensive agents, anti-inflammatory drugs, and treatments for neurological disorders. Its versatility arises from its ability to undergo nucleophilic substitution, cross-coupling reactions, and other functional group modifications, making it a flexible starting material for complex synthesis.

The compound is also useful in the development of agrochemicals. Many modern pesticides, herbicides, and fungicides are based on heterocyclic scaffolds, and 5-(tert-butyl)-2-chloropyridine provides a platform for synthesizing compounds with enhanced activity and selectivity. The tert-butyl group helps improve the compound’s resistance to metabolic breakdown, thus increasing the longevity of the active ingredient in agricultural applications. The chlorine group enables functionalization that can tailor the biological properties to target specific pests or plant diseases.

In material science, 5-(tert-butyl)-2-chloropyridine plays a role in the synthesis of specialty polymers and liquid crystals. Pyridine derivatives are often incorporated into materials to impart unique electronic or optical properties. The tert-butyl group contributes to structural rigidity and thermal stability, while the chlorine atom allows for controlled modification of the material’s properties. Such materials find applications in displays, sensors, and electronic components where high performance and durability are required.

The synthesis of 5-(tert-butyl)-2-chloropyridine typically involves the selective chlorination of pyridine derivatives followed by the introduction of the tert-butyl group through Friedel-Crafts alkylation or other alkylation methods. Advances in synthetic methods have improved the yield and efficiency of this process, making the compound more accessible for industrial applications.

Research into 5-(tert-butyl)-2-chloropyridine continues to expand, particularly in the exploration of new derivatives for drug discovery and material innovation. Its unique combination of steric and electronic properties ensures that it remains a valuable tool in the chemist’s toolkit. As industries demand more specialized molecules with tailored properties, compounds like 5-(tert-butyl)-2-chloropyridine will continue to play an important role in scientific and technological advancements.

References

1. Synthesis: Griffin, W. C. (1949). "Synthesis of polyoxyethylene (20) sorbitan monolaurate." Journal of the Society of Cosmetic Chemists, 1(5), 311�326.

2. Applications: Rowe, R. C. (2009). "Emulsifiers in pharmaceuticals: Polyoxyethylene (20) sorbitan monolaurate." Pharmaceutical Development and Technology, 14(1), 1�8.
DOI: 10.1080/10837450802409539

3. Review: Schott, H. (1995). "Nonionic surfactants: Polyoxyethylene sorbitan esters." Journal of Pharmaceutical Sciences, 84(11), 1269�1277.
DOI: 10.1002/jps.2600841102