Study On Synthesis Of Methylcyclopentadecanone

Musk is a kind of precious natural spices and herbs, and it is hard to meet the demand as the endangered musk deer and rare production. With disclosure of the toxicity and the impact on the ecological problems of the nitro and polycyclic musk spices, and as more friendly muscone and 2-methylcyclopentadecanone to the human and the environment, synthetic chemists are interested in the research and development of large ring musk again. Therefore, the research and development of new synthesis methods of methylcyclopentadecanone is of great significance both in theory and in practice for the synthesis of macrocyclic compounds.The first part of this thesis is the synthesis of muscone. We designed a novel synthesis route by 6 steps which used relatively cheap 1,15-pentadecanedioic acid as the starting material. Muscone was successfully synthesized in total 23% yield. By esterification of 1,15-pentadecanedioic and methanol, we got dimethyl 1,15-pentadecandioate with the yield of 97%. By benzoin condensation cyclization reaction under the action of sodium metal,2-hydroxycyclopentadecanone was synthesized from the ester in 81% yield. The ester can be reacted in 0.3 mol/L as relatively high concentrations which achieved good kettle efficiency. Under the action of hydroiodic acid, cyclopentadecanone was synthesized from 2-hydroxycyclopentadecanone in 85% yield. Then, bromination of cyclopentadecanone by using the cheaper 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), we got 2-bromocyclopentadecan-l-one in 84% yield. And then we used lithium carbonate to debrominate to get 2-cyclopentadecen-l-one in 56% yield. Finally, bromomethane was successfully used instead of the expensive iodomethane to prepare Grignard reagent. Following by reacting with 2-cyclopentadecen-l-one, target product(muscone) was synthesized in 73% yield by 1,4-addition reaction. This study on the synthesis of muscone has theoretical and practical value.The second part of this thesis is the synthesis of 2-methylcyclopentadecanone. A novel synthesis route to get 2-methylcyclopentadecanone in total 24% yield in 6 steps with relatively easy getting 1,15-pentadecanedioic acid as the starting material was designed. By esterification reaction, we obtained in 97% yield. Treatment the ester with sodium metal and trimethylchlorosilane, we obtained the corresponding silyl enol ethers in 86% yield. With zinc bromide as Lewis acid, acetic acid-(phenylsulfanyl-methyl ester) as methylating reagent, silicon enol ethers:zinc bromide:acetic acid-(phenylsulfanyl-methyl ester)= 2:1:1 as material ratio, 2-hydroxy-2-(phenylthiomethyl)-cyclopentadecanone was successfully synthesized in 46% yield. Then treatment of the product in 45% hydroiodic acid, 2-(phenylthiomethyl)cyclopentadecanone was synthesized with yield of 76%. Finally, reduction by Raney Ni in the mixed solvent of acetone and ethanol at room temperature, we got 2-methylcyclopentadecanone in 83% yield. The novel synthesis route with mild reaction condition and facile material, especially using the new method of methylation instead of using Grignard reagent and the expensive iodomethane make it brief and easy to operate.