2-tert-Butylthiophene

Synthetic Routes and Reaction Conditions: 2-tert-Butylthiophene can be synthesized through several methods. One common approach involves the alkylation of thiophene with tert-butyl halides in the presence of a strong base. For example, the reaction of thiophene with tert-butyl bromide in the presence of a base such as potassium tert-butoxide can yield this compound .

Industrial Production Methods: Industrial production of this compound typically involves similar alkylation reactions but on a larger scale. The reaction conditions are optimized to maximize yield and purity, often involving the use of continuous flow reactors and advanced purification techniques .

Types of Reactions: 2-tert-Butylthiophene undergoes various chemical reactions, including:

Oxidation: It can be oxidized to form thiophene oxides and dioxides.

Reduction: Reduction reactions can convert this compound to its corresponding dihydrothiophene derivatives.

Substitution: Electrophilic substitution reactions can introduce various functional groups into the thiophene ring.

Common Reagents and Conditions:

Oxidation: m-Chloroperbenzoic acid, hydrogen peroxide.

Reduction: Lithium aluminum hydride.

Substitution: Nitric acid, sulfuric acid.

Major Products Formed:

Oxidation: Thiophene oxides and dioxides.

Reduction: Dihydrothiophene derivatives.

Substitution: Nitrothiophene, sulfonated thiophene.

Organic Synthesis

Building Block for Complex Molecules
2-tert-Butylthiophene serves as a versatile building block in organic synthesis. It is used to create more complex molecules, including pharmaceuticals and agrochemicals. The presence of the tert-butyl group enhances steric hindrance, which can be beneficial in controlling reaction pathways and selectivity.

Biological Research

Potential Biological Activities
Research indicates that thiophene derivatives, including this compound, exhibit promising biological activities. Studies have focused on their antimicrobial and anticancer properties, making them candidates for further investigation in medicinal chemistry.

Material Science

Organic Semiconductors and Light-Emitting Diodes (LEDs)
In material science, this compound is utilized in the development of organic semiconductors and LEDs. Its electronic properties contribute to the efficiency of devices used in optoelectronics.

Case Study 1: Antimicrobial Activity

A study published in a peer-reviewed journal examined the antimicrobial effects of this compound against various bacterial strains. The compound demonstrated significant inhibition at certain concentrations, suggesting its potential as an antimicrobial agent.

Case Study 2: Photodynamic Therapy

Research on thiophene derivatives has highlighted their role as photosensitizers in photodynamic therapy (PDT). A mathematical model was developed to predict their reactivity toward singlet oxygen, emphasizing the importance of stability and degradation rates for effective treatment outcomes .

The mechanism of action of 2-tert-Butylthiophene depends on its specific application. In medicinal chemistry, thiophene derivatives often interact with biological targets such as enzymes and receptors. For example, they may inhibit enzymes involved in inflammatory pathways or modulate receptor activity to exert therapeutic effects . The presence of the tert-butyl group can influence the compound’s binding affinity and selectivity for its molecular targets .

Thiophene: The parent compound, lacking the tert-butyl group.

2-Methylthiophene: A similar compound with a methyl group instead of a tert-butyl group.

2-Butylthiophene: A compound with a butyl group at the second position.

Comparison: 2-tert-Butylthiophene is unique due to the presence of the bulky tert-butyl group, which can influence its steric and electronic properties. This can affect its reactivity and interactions with other molecules, making it distinct from other thiophene derivatives. For example, the tert-butyl group can provide steric hindrance, reducing the compound’s susceptibility to certain reactions compared to smaller substituents like methyl or butyl groups .

2-tert-Butylthiophene (C₈H₁₂S) is a sulfur-containing heterocyclic compound recognized for its diverse biological activities. This article reviews the biological activity of this compound, focusing on its effects in various biological systems, including antimicrobial properties, potential as a photosensitizer in photodynamic therapy (PDT), and its interaction with biological receptors.

Chemical Structure and Properties

This compound is characterized by a thiophene ring substituted with a tert-butyl group at the second position. Its chemical structure contributes to its unique reactivity and biological properties.

Biological Activity Overview

The biological activities of this compound have been explored through various studies, revealing significant effects on microbial organisms and potential therapeutic applications.

1. Antimicrobial Activity

Research has indicated that this compound exhibits antimicrobial properties against various bacterial strains. A study highlighted its efficacy in disrupting cell membranes of Gram-positive and Gram-negative bacteria, suggesting a mechanism involving cell lysis.

2. Photodynamic Therapy (PDT) Potential

Recent studies have evaluated the use of this compound as a photosensitizer in PDT. Its ability to generate reactive oxygen species (ROS) upon light activation makes it a candidate for cancer treatment.

• Mechanism : Upon irradiation, this compound interacts with singlet oxygen, leading to cytotoxic effects on tumor cells.
• Efficacy : In vitro studies demonstrated that cells treated with this compound and exposed to light exhibited significant reductions in viability compared to controls.

Case Studies

Case Study 1: Antimicrobial Efficacy
A study conducted by researchers at the University of Groningen assessed the antimicrobial activity of various thiophene derivatives, including this compound. The findings indicated that this compound effectively inhibited the growth of pathogenic bacteria, supporting its potential use in developing new antimicrobial agents .

Case Study 2: Photodynamic Applications
In a recent publication, researchers explored the photodynamic effects of thiophene derivatives, including this compound. The results showed enhanced cytotoxicity against cancer cells when combined with specific wavelengths of light, indicating promising applications in cancer therapy .

The biological activity of this compound can be attributed to several mechanisms:

• Cell Membrane Disruption : The compound's hydrophobic nature allows it to integrate into bacterial membranes, leading to increased permeability and eventual cell death.
• Reactive Oxygen Species Generation : In PDT applications, the compound generates ROS upon light activation, which can induce apoptosis in cancer cells.

Q. Basic: What are the standard synthetic routes for 2-tert-Butylthiophene, and how can purity be validated experimentally?

Methodological Answer:
The most common synthesis involves Friedel-Crafts alkylation of thiophene with tert-butyl halides or alcohols, using Lewis acids like AlCl₃ . Key steps include:

• Purification : Column chromatography (silica gel, hexane/ethyl acetate) followed by recrystallization.
• Purity Validation :
  • NMR Spectroscopy : Compare ¹H/¹³C NMR shifts with literature data (e.g., tert-butyl protons at δ ~1.3 ppm) .
  • GC-MS : Monitor retention times and molecular ion peaks (m/z = 154 for C₈H₁₂S) to confirm absence of side products .
• Elemental Analysis : Required for novel derivatives to confirm stoichiometry .

Q. Advanced: How can researchers resolve contradictions in reported spectroscopic data for this compound derivatives?

Methodological Answer:
Contradictions often arise from solvent effects, impurities, or isomerization. A systematic approach includes:

• Replication Studies : Reproduce synthesis and characterization under controlled conditions (e.g., inert atmosphere, anhydrous solvents) .
• Literature Cross-Validation : Use SciFinder with CAS Registry Numbers (e.g., 20662-84-4 for 2-tert-Butylthiophene) to filter high-quality studies .
• Computational Validation : Compare experimental NMR shifts with density functional theory (DFT)-predicted values (e.g., B3LYP/6-311+G(d,p)) to confirm assignments .

Q. Basic: What analytical techniques are essential for characterizing this compound’s electronic and steric properties?

Methodological Answer:

• UV-Vis Spectroscopy : Measure λₘₐₓ to assess conjugation effects (thiophene ring π→π* transitions ~240–260 nm).
• Cyclic Voltammetry : Determine oxidation potentials to evaluate electron-richness (e.g., E₁/₂ ~1.2 V vs. Ag/AgCl) .
• X-ray Crystallography : Resolve steric bulk of the tert-butyl group (bond angles and torsional strain) .

Q. Advanced: How to design experiments to study the steric effects of the tert-butyl group on this compound’s reactivity in cross-coupling reactions?

Methodological Answer:

• Comparative Studies : Synthesize analogs (e.g., 2-methylthiophene) and compare reaction kinetics in Suzuki-Miyaura couplings.
• Kinetic Isotope Effects (KIE) : Use deuterated substrates to probe steric vs. electronic influences .
• DFT Modeling : Calculate transition-state geometries (e.g., using Gaussian) to visualize steric hindrance .
• In-situ Monitoring : Employ ReactIR to track intermediate formation under varying steric conditions .

Q. Advanced: What computational methods are suitable for predicting the regioselectivity of electrophilic substitutions in this compound?

Methodological Answer:

• Frontier Molecular Orbital (FMO) Analysis : Identify HOMO localization (typically at C5 due to tert-butyl’s steric blockade at C2) .
• Molecular Electrostatic Potential (MEP) Maps : Visualize electron density to predict electrophile attack sites.
• MD Simulations : Simulate solvent effects (e.g., THF vs. DMF) on reaction pathways using GROMACS .

Q. Basic: How to conduct a systematic literature review on this compound’s applications in organic electronics?

Methodological Answer:

• Keyword Strategy : Combine terms like “this compound,” “charge transport,” and “HOMO-LUMO” in SciFinder/Reaxys .
• Filter by Methodology : Prioritize studies with in-situ characterization (e.g., grazing-incidence XRD for thin-film morphology) .
• Citation Tracking : Use Web of Science to trace seminal papers (e.g., conductivity studies post-2010) .

Q. Advanced: How can researchers address discrepancies in reported catalytic activity of this compound-containing metal complexes?

Methodological Answer:

• Control Experiments : Test catalyst stability under reaction conditions (e.g., TGA for thermal decomposition).
• Surface Analysis : Use XPS or TEM to verify metal oxidation states and nanoparticle dispersion .
• Collaborative Reproducibility : Share catalyst samples with independent labs for benchmarking .