Phosphorus oxychloride can be used in the formylation (Vilsmeier-Haack) reaction of aromatic rings, phosphorylation reagents, amide dehydration reagents, alcohols, phenols and heterocyclic halogenating reagents.
1. Methylene ammonium chloride
Phosphorus oxychloride is a strong Lewis acid and is widely used in the synthesis of amino resins. Of particular importance is its reaction with substituted amides (such as DMF or DMA) to give methylene ammonium chloride salts (Formula 1). These salts (Vilsmeier-Haack reagents) are intermediates with high reaction diversity and can participate in a variety of important organic reactions, such as Vilsmeier-Haack reaction and Bischler-Napieralski reaction.
2. Formylation of aromatic rings
The Vilsmeier-Haack reagent attacks the aromatic ring with rich electron density to produce aromatic methylene ions. After hydrolysis, formylated aromatic compounds are obtained. Many aromatic compounds can be formylated in this manner, including monobenzene and polynuclear aromatic derivatives (Formula 2) [1].
Many aromatic heterocycles such as pyrrole, thiophene, furan, indole, quinoline, and purine can react with phosphorus oxychloride in DMF. Pyrrole, thiophene, and furan generally react at the 2-position or 5-position, and indole reacts at the 2-position or 5-position. Indole reacts at the 3-position (Formula 3) [2].
3. Synthesis of olefins from secondary and tertiary alcohols by dehydration
Phosphorus oxychloride is also used in dehydration reactions (Formula 4)[3].
4. Bischler-Napieralski reaction
Phosphorus oxychloride is also used in Bischler-Napieralski reaction [4,5], N-disubstituted amides
Under its catalytic action, the ring is closed to form isoquinoline (Formula 5)[4].
5. Chlorinated thermoplastic elastomers of heterocyclic compounds
POCl3 is also a common reagent for chlorinating heterocycles, usually containing ketone and alcohol functional groups
Chlorination of purine, pterin and isoxazole (Formula 6)[6,7].
6. Phosphorylation reaction
POCl3 is also a commonly used reagent for phosphorylating alcohols, amines and thiol heterocycles. After diols and diamines react with POCl3 and then hydrolyzed, phosphate esters or amides with a cyclic structure can be obtained (Formula 7) [8,9 ].
7. Catalysis of thioacetal and ketone reactions
Catalyzed by phosphorus oxychloride and montmorillonite, aldehydes, ketones and disulfide compounds react at room temperature
A better yield can be obtained (Formula 8)[10].
