Synthesis of 1,8‐Cineole Derivatives from 3‐Carene

Abstract

AbstractWith the purpose of developing high‐value utilization approach for 3‐carene, various 1,8‐cineole derivatives bearing Br, OH, and NH2 groups at C‐6 were synthesized starting from it, following a new method of synthesis. The structure of 1,8‐cineole was established from the structure of carene by first introducing an OH and then carrying out ring‐opening and nucleophilic substitution reactions under acidic conditions. Br was simultaneously introduced at C‐6 as an active reaction site. The acidity of the medium significantly influenced the efficiency of the reaction. It was observed that trimethylsilyl bromide was the ideal reagent to carry out the reaction. 6‐Bromo‐1,8‐cineole was prepared from 3‐carene via a two‐steps process at 20 °C. The reaction time was ≤3 h. The maximum extent of conversion was 98.58 % and a selectivity of 60.66 % was achieved. Then, we synthesized two other compounds with high reactivities from 6‐bromo‐1,8‐cineole. 6‐Hydroxyl‐1,8‐cineole was synthesized by reacting 6‐bromo‐1,8‐cineole with H2O at 65 °C for 1 h. The extent of conversion was 98.49 % and the selectivity was 87.86 %. A hydroxyl derivative with >90 % purity was obtained after removing the solvent. 6‐Amino‐1,8‐cineole together with 6‐hydroxyl‐1,8‐cineole were synthesized by reacting 6‐bromo‐1,8‐cineole with ammonia with the conversion was >98 % under 70 °C for 1 h. Lower feed ratio of ammonia to 6‐bromo‐1,8‐cineole was good for the yield of amino derivative. The hydroxyl/amino ratio decreased from 4.0 to 1.6 with the feed ratio decreased from 8 to 4. The hydroxyl derivative and amino derivative could be efficiently separated by adjusting the pH of the reaction medium to obtain an amino derivative (>93 % purity).