Synthetic Studies Of (S)-Methoprene Intermediate

(S)-Methoprene is a new insect growth regulator with juvenile hormone activity, which has been applied to controlling many kinds of insects due to its innocuity, high activity and high selectivity.In this thesis, (2Z, 4E, 7S)-11- Methoxy-3, 7, 11-trimethyl-2, 4-dodecadienoic acid (MTDDA), which is an important intermediate of (S)-Methoprene is synthesized.The synthentical process of Methyl Isodehydroactate (MIDA) was improved. The selection of MIDA process and optimal synthesis condition were studied in details. Under methyl acetoacetate (MAA) as substrate, anhydrous methanol as solvent, dryness HC1 as catalyst, MIDA is prepared by means of MAA self-condensation. The effect of reaction condition on the yield of MIDA was discussed, and the optimal reaction conditions were determined. When the reaction system was dry, the feeding ratio of methanol to MAA was 1:2, reaction time was about 72h, the feeding ratio of HC1 to MAA was 3, the overall mol yield of MIDA is achieved with about 82% which is more than the yield of the prior literature, The purity of MIDA is obtained with nearly 100% after methanol re-crystallized, The improved process of MIDA made it possible to be industrialized. On the other hand, the reaction mechanism was discussed in details.The process of synthesis MTDDA was improved. From the starting material (3S)-methoxycitronlellal reacting with MIDA via Knoevenagel aldol condensation, followed by acid hydrolyzed, decarboxylated in the presence of single organic alkali-2, 4-dimethylpyridine, after re-hydrolyzed, MTDDA as the target products was succeededly synthesized. HPLC analysis showed the purity was 96%, IR and 'H-NMR spectra analysis confirmed the 2Z,4E stereoisomer, the optical rotation was [α ]_D²⁰=+18.2° (c=0. 5, n-hexane). The overall yield of MTDDA was 85%.The process of synthesizing high optically active citronellal derivative due to its high expensive cost was explored. The catalyst consisting of optically active ligand (+)-BINAP and transition metal complex bis(cycloocta-l,5-diene)-μ,μ' -dichloro-dirhodium was used to catalyze isomerization of prochiral allylamine N, N-diethyl geranylamine(GDEA) in synthesis of optical active citronellal. First, high purity of GDEA was achieved through reacting myrcene with DEA. The selection of GDEA process and optimal synthesis condition were studied in details, and the optimal reaction conditions of synthesis GDEA were as follows: reaction solvent cyclohexane, catalyst lithium, the feeding mol ratio of DEA to myrcene2.5:l, the catalyst mol ratio to myrcene 15%, reaction temperature 70 °C, reaction time 12 h. After rectified, the purity of GDEA can reached 98%.In the thesis, high purity of transition metal complex bis(cycloocta-l,5-diene)-u,n'-dichlorodirhodium and optical active catalyst [(R)-(+)-binap-cycloocta-l, 5-diene] rhodium (I) perchlorate was successfully prepared. The product was characterized by melting point > infrared spectra, element analysis and !H-NMR spectra.Last, the process of synthesizing high optical active (S)-citronellal derivatives were experimental explored. Such factors as oxygen, moisture, carbon dioxide etc, cause the high active catalyst extremely sensitive to impurities, which may be the reasons of the catalyst poisoning during the reaction, and made the experiment fail. The isomerization reaction need to be further researched in the future.