Researchers have unveiled a significant advancement in the production of 4,6-dichloropyrimidine, a crucial intermediate for pharmaceutical sulfonamides and the fungicide azoxystrobin. Traditional synthesis methods have long suffered from environmental drawbacks, notably the generation of vast quantities of difficult-to-treat phosphorus-containing wastewater and complex purification processes. The newly developed solvent-free technique promises to overcome these hurdles, offering a more sustainable and efficient industrial solution.

The core innovation lies in utilizing thionyl chloride (SOCl₂) in a dual role: acting simultaneously as the chlorinating agent and the solvent. This eliminates the need for problematic additional solvents, such as highly toxic ethylene dichloride previously employed in alternative processes. The reaction employs N,N-dimethylaniline (DMA) as a catalyst under carefully optimized conditions.

The step-by-step synthesis process is outlined as follows:
1. Charging: Mixing 4,6-dihydroxyprimidine with thionyl chloride at a molar ratio ranging between 1:4 to 1:8, with an optimal ratio of 1:6-1:8.
2. Catalyst Addition: Adding DMA slowly at 40-60°C (optimally 50-60°C) over 1-3 hours. The molar ratio of 4,6-dihydroxyprimidine to DMA is 1:2.1-2.3, ideally 1:2.2-2.3.
3. Reaction Completion: Holding the temperature for 2-4 hours (optimally 3-4 hours) to ensure complete reaction, then cooling to room temperature.
4. Thionyl Chloride Recovery: Transferring the reaction mixture to a distillation setup. Excess thionyl chloride is efficiently reclaimed via vacuum distillation, achieving recovery rates of 92-93.6% and purity levels of 99-99.3%.
5. Product Isolation: Continuing distillation under vacuum to isolate 4,6-dichloropyrimidine as a white crystalline solid. This direct distillation eliminates the need for cumbersome recrystallization, yielding product with exceptional purity between 99.2-99.6% and high yields of 92.8-95.6% (optimally 94.5-95.6%).
6. Catalyst Recovery: Treating the residual pot mixture with 26% sodium hydroxide solution, adjusting to pH 8-9. Stirring and settling allow for the facile recovery of the N,N-dimethylaniline layer (DMA) with high purity (98.8-99.3%) and excellent recovery rates (90-93.3%). Recovered DMA and thionyl chloride are readily reusable in subsequent batches.

The environmental impact is dramatically improved. Wastewater generation is slashed to approximately 6-7 kg per 1 kg of 4,6-dichloropyrimidine produced. This wastewater primarily consists of sodium sulfite and sodium chloride, amenable to concentration and salt crystallization. The near-complete recycling of reagents minimizes raw material consumption and environmental discharge.

Demonstrated across multiple experimental runs (Examples 1-3), the synthesis consistently delivered high-quality 4,6-dichloropyrimidine and achieved efficient recovery of both SOCl₂ and DMA. Compared to existing methods relying on phosphoryl chloride (POCl₃) or phosgene, this route stands out for its simplicity, reduced environmental footprint, and economic benefits stemming from high efficiency and reagent recycling. Example 2 highlights optimal results: product purity of 99.6% and product yield of 95.6%, alongside SOCl₂ recovery of 93.6% (99.3% pure) and DMA recovery of 93.3% (99.3% pure).

In conclusion, this solvent-free synthesis using thionyl chloride represents a major leap forward for the industrial production of 4,6-dichloropyrimidine. By integrating dual reagent function and enabling substantial recovery, the method delivers exceptional purity, yield, cost-effectiveness, and environmental sustainability, effectively addressing the core limitations of traditional techniques and meeting the growing demand for this essential pharmaceutical and agrochemical building block.