Cannabigerol Synthesis and Sequential Distillation-Extraction Purification

The patent changes the physical parameters of the reaction system by controlling temperature gradients during distillation and adjusting liquid-liquid extraction phase ratios to achieve high purity CBG separation without chromatographic methods. The distillation process uses specific temperature ranges (60-80°C for initial distillation, 100-120°C for final distillation) to selectively vaporize and condense CBG while leaving impurities behind.

The patent replaces the mechanical/chromatographic purification system with a thermal distillation system and liquid-liquid extraction system. Instead of using chromatography columns with stationary phases, the invention uses temperature-controlled distillation apparatus and solvent-based extraction, thereby eliminating the need for expensive chromatographic materials and reducing production time.

The patent divides the purification process into multiple sequential stages: first distillation to remove low-boiling impurities, liquid-liquid extraction to remove intermediate impurities, and second distillation to remove high-boiling impurities. Each stage targets specific types of impurities, progressively increasing purity to >99% without requiring expensive chromatographic methods.

The patent employs a composite purification approach combining two different separation mechanisms: distillation (based on volatility differences) and liquid-liquid extraction (based on solubility differences). This composite method leverages the complementary strengths of both techniques to achieve high purity removal of diverse impurity types that would be difficult to eliminate with a single method.

The patent introduces a preliminary step before the main Friedel-Crafts alkylation reaction: converting olivetol to its methyl ether derivative. This preliminary protection of the phenolic hydroxyl group prevents it from participating in unwanted side reactions and directs the alkylation to occur only at the desired aromatic ring position, thereby improving selectivity while maintaining production efficiency.

The patent uses a methyl ether intermediate as a mediator in the synthesis pathway. The methyl ether group acts as a temporary protecting group that modulates the reactivity of olivetol during the Friedel-Crafts reaction, ensuring selective alkylation at the correct position. After the alkylation is complete, the methyl ether is removed to yield the final CBG product with high selectivity.