六水合三氯化铁催化3-甲基环己酮与丙酮酸乙酯交叉羟醛缩合制备薄荷内酯

doi:10.3724/SP.J.1095.2013.20523

摘要/Abstract

摘要： 用FeCl3·6H2O催化3-甲基环己酮与丙酮酸乙酯交叉羟醛缩合，制得2-(2-氧代-4-甲基环己叉基）丙酸乙酯和7a-羟基薄荷内酯，皂化后用硼氢化钠还原、酸化制得(±)-薄荷内酯,产率为51％。考察了3-甲基环己酮的烯醇式异构化的位置选择性和粗产物中(±)-薄荷内酯与(±)-异薄荷内酯异构体的比例。

关键词: 甲基环己酮, 丙酮酸乙酯, 六水合三氯化铁催化剂, 交叉羟醛缩合, 薄荷内酯

Abstract: A FeCl3·6H2O-catalyzed cross-Aldol condensation of 3-methylcyclohexanone and ethyl pyruvate was developed for the synthesis of mintlactone. The resultant ethyl 2-(4-methyl-2-oxocyclohexylidene) propionate and 7a-hydroxymintlactone were saponified by NaOH, reduced by NaBH4, and acidified to yield (±)-mintlactone in 51% yield. Regioselectivity of the keto-to-enol isomerization of 3-methylcyclohexanone and isomer ratio of (±)-mintlactone/(±)-isomintlactone in crude products were discussed.

Key words: methylcyclohexanone, ethyl pyruvate, ferric chloride hexahydrate catalyst, cross-Aldol condensation, mintlactone

中图分类号:

O624.5

陈雄, 刘金云, 李亚白, 刘建福, 杨华武. 六水合三氯化铁催化3-甲基环己酮与丙酮酸乙酯交叉羟醛缩合制备薄荷内酯[J]. 应用化学, DOI: 10.3724/SP.J.1095.2013.20523.

CHEN Xiong, LIU Jinyun, LI Yabai, LIU Jianfu, YANG Huawu*. Synthesis of Mintlactone via Cross-Aldol Condensation Between 3-Methylcyclohexanone and Ethyl Pyruvate Using Ferric Chloride Hexahydrate as Catalyst[J]. Chinese Journal of Applied Chemistry, DOI: 10.3724/SP.J.1095.2013.20523.

参考文献

[１] Gaudin J M. Synthesis and Organoleptic Properties of p-Menthane Lactones[J]. Tetrahedron,2000,56(27):4769-4776.

[２] Serra S,Fuganti C. Enzyme-Mediated Preparation of Enantiomerically Pure p-Mentha-3,9-diols and Their Use for the Synthesis of Natural p-Menthane Lactones and Ethers[J]. Helv Chim Acta,2002,85(8):2489-2502.

[３] Ferraz H M C,Jr L S L,Grazini M V A. Syntheses of Mintlactone and Isomintlactone[J]. Synthesis,2002,34(15):2155-2164.

[４] Bates R W,Sridhar S J. A Synthesis of (-)-Mintlactone[J]. J Org Chem,2008,73(20):8104-8105.

[５] Tsubuki M,Takahashi K,Honda T. Practical Ruthenium-Catalyzed Cyclocarbonylation of Allenyl Alcohols in 2,4,6-Collidine Leading to α,β-Unsaturated Lactones:Concise Stereoselective Synthesis of (+)-Isomintlactone[J]. J Org Chem,2009,74(3):1422-1425.

[６] Gao P,Xu P F,Zhai H B. Expeditious Construction of (+)-Mintlactone via Intramolecular Hetero-Pauson-Khand Reaction[J]. J Org Chem,2009,74(6):2592-2593.

[７] Tanabe Y,Mitarai K,Higashi T,et al. Efficient One-step Synthesis of Trialkylsubstituted 2(5H)-Furanones Utilizing Direct Ti-crossed Aldol Condensation and Its Application to the Straightforward Synthesis of (R)-Mintlactone and (R)-Menthofuran[J]. Chem Commun,2002,38(21):2542-2543.

[８] Bolm C,Legros J,Paih J L,et al. Iron-Catalyzed Reactions in Organic Synthesis[J]. Chem Rev,2004,104(12):6217-6254.

[９] Liu L X. Recent Uses of Iron Catalysts in Organic Reactions[J]. Curr Org Chem,2010,14(11):1099-1126.

[１０] Aoyama N,Manabe K,Kobayashi S. Iron(Ⅲ) Chloride as a Water-Compatible Lewis Acid for Diastereoselective Aldol Reactions in Water in the Presence of a Surfactant[J]. Chem Lett,2004,33(3):312-313.

[１１] Zhang X Y,Fan X S,Niu H Y,et al. A Novel Green Preparation of α,α′-Bis(substituted benzylidene)-cycloalkanones Promoted by FeCl3·6H2O in Ionic Liquid[J]. Chinese Chem Lett,2003,14(10):1005-1007.

[１２] Li H J,Li W J,Li Z P. Iron-catalyzed Cross-aldol Reactions of ortho-Diketones and Methyl Ketones[J]. Chem Commun,2009,45(22):3264-3266.

[１３] Crisp G T,Meyer A G. Synthesis of Optically Active α-Methylene γ-Butyrolactones and (+)-Mintlactone[J]. Tetrahedron,1995,51(20):5831-5846.

[１４] Antony A,Maloney T. The Effect of Solvent and Cation on the Isomer Ratio of the Enolates of 3-Methylcyclohexanone[J]. J Org Chem,1972,37(7):1055-1056.

[１５] Frérot E,Bagnoud A,Vuilleumier C. Menthofurolactone:A New p-Menthane Lactone in Mentha piperita L.:Analysis, Synthesis and Olfactory Properties[J]. Flavour Fragr J,2002,17(3):218-226.

[16] Fujita T,Watanabe S,Miharu K,et al. A Convenient Preparative Method for Mintlactone and Isomintlactone[J]. J Chem Tech Biotechnol,1985,35(2):57-62.