哈格曼酯

哈格曼酯
	IUPAC名; Ethyl 2-methyl-4-oxocyclohex-2-ene-1-carboxylate
別名	2-甲基-4-氧代環己-2-烯-1-酸乙酯
識別
CAS號	487-51-4
PubChem	79020
ChemSpider	71353
SMILES	O=C(OCC)C1C(=C\C(=O)CC1)/C;
InChI	1/C10H14O3/c1-3-13-10(12)9-5-4-8(11)6-7(9)2/h6,9H,3-5H2,1-2H3;
InChIKey	VLTANIMRIRCCOQ-UHFFFAOYAX
EINECS	207-657-4
性質
化學式	C10H14O3
摩爾質量	182.22 g·mol−1
密度	1.078 g/mL
沸點	268-272 °C（541-545 K）
	若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

哈格曼酯是一種有機化合物，化學式 C₁₀H₁₄O₃。它是在1893年由德國化學家卡爾·哈格曼（英語：Carl Hagemann）首次製備和描述的。這種化合物在有機化學中用作試劑，製備許多包括固醇、三孢酸（英語：trisporic acid）和類萜等各種天然產物。

製備

哈格曼的方法

二碘甲烷和兩倍量的乙酰乙酸乙酯在甲醇鈉存在下反應，形成2,4-二乙酰基戊烷的二乙酯。這個前體之後和鹼反應來環化，最後加熱，產生哈格曼酯。^[1]^[2]

Knoevenagel的方法

在Hagemann之後不久，Emil Knoevenagel（英語：Emil Knoevenagel）描述了在催化量的哌啶下，甲醛和兩當量的乙酰乙酸乙酯的反應也可以生產相同的中間體——2,4-二乙酰基戊烷二乙酯。^[2]

Newman和Lloyd的方法

2-甲氧基-1,3-丁二烯和2-丁炔酸乙酯經過狄爾斯–阿爾德反應，形成水解產生哈格曼酯的前體。通過在反應物丁炔酸酯中加入取代基，允許合成不同的C2烷基化哈格曼酯衍生物。^[2]

用處

哈格曼酯已被用作許多全合成中的關鍵構建塊。^[2]例如，真菌激素三孢酸的關鍵中間體是通過哈格曼酯的烷基化而成的。^[3]它也用於製備固醇。^[4]其他作者也將其用於狄爾斯–阿爾德反應，產生倍半萜二聚體^[5]，或是形成簡單衍生物。^[6]^[7]^[8]

參考資料

^ Hagemann, C. Th. L. Ueber die Einwirkung von Methylenjodid auf Natracetessigäther. Berichte der Deutschen Chemischen Gesellschaft. 1893, 26: 876–890 [2021-11-20]. doi:10.1002/cber.189302601181. （原始內容存檔於2021-11-20）（德語）.
^ ^2.0 ^2.1 ^2.2 ^2.3 Pollini, Gian Piero; Benetti, Simonetta; De Risi, Carmela; Zanirato, Vinicio. Hagemann's ester: a timeless building block for natural product synthesis. Tetrahedron. 2010, 66 (15): 2775–2802. doi:10.1016/j.tet.2010.01.078.
^ White, James D.; Sung, Wing Lam. Alkylation of Hagemann's ester. Preparation of an intermediate for trisporic acid synthesis. The Journal of Organic Chemistry. 1974, 39 (16): 2323–2328. doi:10.1021/jo00930a001.
^ Hogg, John A. Synthetic Sterols. I. Model Experiments Employing Hagemann's Ester. Journal of the American Chemical Society. 1948, 70 (1): 161–164. PMID 18918810. doi:10.1021/ja01181a047.
^ Liu, Bo; Yang, Li; Yue, Guizhou; Yuan, Changchun; Du, Biao; Deng, Heping. Synthetic Studies toward Lindenane-Type Sesquiterpenoid Dimers. Synlett. 2014, 25 (17): 2471–2474. doi:10.1055/s-0034-1379001.
^ McAndrew, Bruce A. Ethyl 2- methyl-4-oxocyclohex-2-enecarboxylate (Hagemann's ester) as a precursor to alkyl-substituted 3-methylcyclohexenones. Journal of the Chemical Society, Perkin Transactions 1. 1979: 1837. doi:10.1039/P19790001837.
^ Nasipuri, D.; Mitra, K.; Venkataraman, S. Cyclohexenone derivatives. Part VI. C-3 and C-1 alkylation of Hagemann's ester (Ethyl 2-methyl-4-oxocyclohex-2-enecarboxylate) with alkyl halides and Michael acceptors. Journal of the Chemical Society, Perkin Transactions 1. 1972: 1836. doi:10.1039/P19720001836.
^ Begbie, A. L.; Golding, B. T. A new synthesis of ethyl 2-methyl-4-oxocyclohex-2-enecarboxylate (Hagemann's ester) and its methyl and t-butyl analogues. Journal of the Chemical Society, Perkin Transactions 1. 1972: 602. doi:10.1039/P19720000602.

[Hagemann-1] Hagemann, C. Th. L. Ueber die Einwirkung von Methylenjodid auf Natracetessigäther. Berichte der Deutschen Chemischen Gesellschaft. 1893, 26: 876–890 [2021-11-20]. doi:10.1002/cber.189302601181. （原始內容存檔於2021-11-20）（德語）.

[Pollini-2] 2.0 ^2.1 ^2.2 ^2.3 Pollini, Gian Piero; Benetti, Simonetta; De Risi, Carmela; Zanirato, Vinicio. Hagemann's ester: a timeless building block for natural product synthesis. Tetrahedron. 2010, 66 (15): 2775–2802. doi:10.1016/j.tet.2010.01.078.

[White-3] White, James D.; Sung, Wing Lam. Alkylation of Hagemann's ester. Preparation of an intermediate for trisporic acid synthesis. The Journal of Organic Chemistry. 1974, 39 (16): 2323–2328. doi:10.1021/jo00930a001.

[Hogg-4] Hogg, John A. Synthetic Sterols. I. Model Experiments Employing Hagemann's Ester. Journal of the American Chemical Society. 1948, 70 (1): 161–164. PMID 18918810. doi:10.1021/ja01181a047.

[Liu-5] Liu, Bo; Yang, Li; Yue, Guizhou; Yuan, Changchun; Du, Biao; Deng, Heping. Synthetic Studies toward Lindenane-Type Sesquiterpenoid Dimers. Synlett. 2014, 25 (17): 2471–2474. doi:10.1055/s-0034-1379001.

[McAndrew-6] McAndrew, Bruce A. Ethyl 2- methyl-4-oxocyclohex-2-enecarboxylate (Hagemann's ester) as a precursor to alkyl-substituted 3-methylcyclohexenones. Journal of the Chemical Society, Perkin Transactions 1. 1979: 1837. doi:10.1039/P19790001837.

[Nasipuri-7] Nasipuri, D.; Mitra, K.; Venkataraman, S. Cyclohexenone derivatives. Part VI. C-3 and C-1 alkylation of Hagemann's ester (Ethyl 2-methyl-4-oxocyclohex-2-enecarboxylate) with alkyl halides and Michael acceptors. Journal of the Chemical Society, Perkin Transactions 1. 1972: 1836. doi:10.1039/P19720001836.

[Begbie-8] Begbie, A. L.; Golding, B. T. A new synthesis of ethyl 2-methyl-4-oxocyclohex-2-enecarboxylate (Hagemann's ester) and its methyl and t-butyl analogues. Journal of the Chemical Society, Perkin Transactions 1. 1972: 602. doi:10.1039/P19720000602.

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