1-Tosylpyrrole
[CAS# 17639-64-4]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Pyrroles
• Name: 1-Tosylpyrrole
• Synonyms: 1-(p-Toluenesulfonyl)pyrrole; 1-(4-Methylphenylsulfonyl)pyrrole; 1-[(4-Methylphenyl)sulfonyl]-1H-pyrrole
• Molecular Formula: C₁₁H₁₁NO₂S
• Molecular Weight: 221.28
• CAS Registry Number: 17639-64-4
• EC Number: 627-473-1
• SMILES: CC1=CC=C(C=C1)S(=O)(=O)N2C=CC=C2

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 99 - 102 ºC (Expl.)
• Boiling point: 377.3±35.0 ºC 760 mmHg (Calc.)^*
• Flash point: 182.0±25.9 ºC (Calc.)^*
• Index of refraction: 1.589 (Calc.)^*

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

Safety Data

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

Hazard Classification

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

Discovory and Applicatios

1-Tosylpyrrole is an organosulfur compound derived from pyrrole, a five-membered aromatic heterocycle containing one nitrogen atom, by the introduction of a tosyl (p-toluenesulfonyl) group at the nitrogen position. This modification enhances the chemical stability of the pyrrole ring and introduces a strong electron-withdrawing group that alters its reactivity profile, making 1-tosylpyrrole a useful intermediate in organic synthesis.

The discovery of 1-tosylpyrrole can be traced to developments in sulfonamide chemistry and functionalized heterocycles in the mid-20th century, when chemists began exploring the reactivity of N-substituted pyrroles for use in pharmaceuticals and materials science. Tosylation of heterocyclic amines was a well-established method for protecting nitrogen functionalities, and its application to pyrrole yielded stable N-tosyl derivatives that could be stored and manipulated more easily than their parent compounds. 1-Tosylpyrrole was thus recognized for its utility in reactions requiring controlled nitrogen reactivity.

Synthesis of 1-tosylpyrrole is typically achieved through the reaction of pyrrole with p-toluenesulfonyl chloride in the presence of a base such as triethylamine or pyridine, often carried out in an aprotic solvent like dichloromethane. The reaction proceeds through nucleophilic attack of the pyrrole nitrogen on the sulfonyl chloride, forming the sulfonamide linkage and yielding the N-tosylated product in good yield. The resulting compound is a solid under ambient conditions and can be purified by recrystallization.

In synthetic organic chemistry, 1-tosylpyrrole serves as a valuable building block. The presence of the tosyl group reduces the basicity of the pyrrole nitrogen and blocks it from participating in further reactions, which allows for selective functionalization at the carbon positions of the ring. This property is particularly important in metal-catalyzed cross-coupling reactions, such as Suzuki, Heck, and Sonogashira couplings, where the N-tosyl group helps prevent unwanted side reactions at the nitrogen atom.

1-Tosylpyrrole is also used as a precursor for the construction of more complex heterocyclic frameworks. For instance, the electron-deficient character of the sulfonamide nitrogen facilitates electrophilic substitutions and ring-forming reactions. In the development of natural product analogs and pharmacologically active molecules, 1-tosylpyrrole is a common intermediate that enables the strategic introduction of functional groups while maintaining structural integrity.

Furthermore, the tosyl group can be removed under reductive conditions, typically using reagents like magnesium in methanol or sodium naphthalenide, to regenerate the free pyrrole after other modifications are complete. This makes 1-tosylpyrrole a versatile protective intermediate in multi-step syntheses.

Applications of 1-tosylpyrrole span both academic and industrial research. It has been used in the synthesis of bioactive compounds, including kinase inhibitors, antiviral agents, and molecules with anticancer activity. In material science, pyrrole derivatives including N-tosylated forms are used in the preparation of conducting polymers and organic electronic materials. While 1-tosylpyrrole itself is not directly employed in commercial products, its chemical behavior underpins many synthetic pathways that lead to valuable functional molecules.

In conclusion, 1-tosylpyrrole is a synthetically important derivative of pyrrole that provides enhanced stability and reactivity control in organic reactions. Its role as a protected pyrrole form makes it an essential tool for chemists engaged in heterocycle functionalization, pharmaceutical research, and advanced materials synthesis.

References

2006. Electrolytic Partial Fluorination of Organic Compounds. 83. Anodic Fluorination of N-Substituted Pyrroles and Its Synthetic Applications to gem-Difluorinated Heterocyclic Compounds. The Journal of Organic Chemistry, 71(2).
DOI: 10.1021/jo0520745

2021. Surface electrocoating of single carbon fibre with electroactive 3,4-ethylenedioxythiophene/1-p(tolylsulphonyl) pyrrole copolymer: effect of dielectric constant of solvent. Bulletin of Materials Science, 44(4).
DOI: 10.1007/s12034-021-02578-0