Lawesson's Reagent
[CAS# 19172-47-5]

Identification

• Classification: Organic raw materials >> Organic sulfur compound
• Name: Lawesson's Reagent
• Synonyms: 2,4-Bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide
• Molecular Formula: C₁₄H₁₄O₂P₂S₄
• Molecular Weight: 404.47
• CAS Registry Number: 19172-47-5
• EC Number: 242-855-4
• SMILES: COC1=CC=C(C=C1)P2(=S)SP(=S)(S2)C3=CC=C(C=C3)OC

Properties

• Melting point: 228-231 °C
• Water solubility: decomposes

Safety Data

• Hazard Symbols: GHS02;GHS07 Danger
• Risk Statements: H261-H302-H312-H332
• Safety Statements: P231+P232-P261-P264-P270-P271-P280-P301+P317-P302+P352-P304+P340-P317-P321-P330-P362+P364-P370+P378-P402+P404-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Substances or mixtures which in contact with water emit flammable gases	Water-react.	2	H261
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H312
Substances or mixtures which in contact with water emit flammable gases	Water-react.	3	H261
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

Lawesson's reagent is a well-known sulfurizing agent widely used in organic synthesis to convert carbonyl compounds into their thio analogs. Lawesson's reagent has the chemical formula [(CH₃C₆H₄)₂P₂S₄] and was discovered by Swedish chemist Sven-Olov Lawesson in 1956 while exploring phosphorus-sulfur chemistry. Lawesson's search for an efficient method to synthesize thioesters and other sulfur-containing compounds led to the identification of the reagent. Its structure consists of a phosphorus-sulfur core and two p-methylphenyl groups. The two phosphorus atoms are connected by a sulfur atom to form a P₂S₄ ring, and two aromatic rings are attached to the phosphorus for enhanced stability. It is a yellow crystalline solid that is soluble in organic solvents such as dichloromethane and toluene.

Lawesson's reagent is mainly used to convert carbonyl compounds such as ketones and aldehydes into the corresponding thiocarbonyl derivatives such as thiones and thioesters. This transformation is essential for the synthesis of sulfur-containing heterocycles and biologically active molecules. It is also effective in converting amides to thioamides, which are valuable intermediates in the synthesis of drugs and natural products.

Lawesson's reagent facilitates the synthesis of thiazoles and thiophenes by inserting sulfur into carbon-nitrogen bonds and carbon-carbon bonds, respectively. These heterocycles are important scaffolds in medicinal chemistry and materials science. It is also used to construct thiopyran and thiorolidine rings, which are components of various natural products and synthetic drugs.

In medicinal chemistry, Lawesson's reagent is used to synthesize sulfur analogs of drugs. This modification can enhance the biological activity, stability, and pharmacokinetic properties of the parent compound. It is used to make thiopeptides and other sulfur-containing peptide analogs as protease inhibitors. These compounds are essential for the development of therapeutics for diseases associated with protease activity.

Lawesson's reagent facilitates the synthesis of sulfur-containing polymers with unique electrical properties. These polymers are used in electronic devices, sensors, and batteries. The reagent is used to produce thio- and dithio-dyes, which have applications in the textile and photonic industries due to their stability and color properties.

Lawesson's reagent is used to introduce thioesters and other protecting groups in organic synthesis. These groups can be selectively removed or transformed in subsequent steps, allowing controlled chemical reactions. It allows the interconversion of functional groups such as ketones, amides, and esters into their thio-analogs, providing chemists with tools to modify molecular structures.

References

2021. Lawesson’s Reagent. Name Reactions, 83.
DOI: 10.1007/978-3-030-50865-4_83

2021. Thionation of Aminophthalimide Hindered Carbonyl Groups and Application to the Synthesis of 3,6’-Dithionated Pomalidomides. Synlett, 32(8).
DOI: 10.1055/s-0040-1720460

2021. S-Heterocycle Synthesis. Lawesson’s Reagent in Heterocycle Synthesis, 6.
DOI: 10.1007/978-981-16-4655-3_6