Synlett 2012; 23(8): 1199-1204
DOI: 10.1055/s-0031-1290900
letter
© Georg Thieme Verlag Stuttgart · New York

Consecutive Michael–Claisen Process for Cyclohexane-1,3-dione Derivative (CDD) Synthesis from Unsubstituted and Substituted Acetone[ 1 ]

Dharminder Sharma
Natural Plant Products Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachel Pradesh, India, Fax: +91(1894)230433   Email: pdas@ihbt.res.in
,
Bandna,
Arun K. Shil
Natural Plant Products Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachel Pradesh, India, Fax: +91(1894)230433   Email: pdas@ihbt.res.in
,
Bikram Singh
Natural Plant Products Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachel Pradesh, India, Fax: +91(1894)230433   Email: pdas@ihbt.res.in
,
Pralay Das*
Natural Plant Products Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachel Pradesh, India, Fax: +91(1894)230433   Email: pdas@ihbt.res.in
› Author Affiliations
Further Information

Publication History

Received: 02 November 2011

Accepted after revision: 13 January 2012

Publication Date:
23 April 2012 (online)


Abstract

A long-existing problem of cyclohexane-1,3-dione derivatives (CDD) synthesis from unreactive acetone through consecutive Michael–Claisen process was solved under this study. The practical applicability of this process was tested for a novel compound ethyl 3-(2,4-dioxocyclohexyl)propanoate for up to 20-gram scale. Furthermore, the scope of different acetone derivatives was investigated and resulted with similar consecutive Michael–Claisen process for CDD synthesis. The reaction exhibited remarkable regioselectivity in Michael addition followed by Claisen cyclization. In this process high substrate selectivity was observed for CDD ­synthesis following consecutive double-Michael–Claisen and ­Michael–Claisen cyclization.

Supporting Information

 
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  • 13 Experimental Procedure for Ethyl 3-(2,4-Dioxocyclohexyl)propanoate (1): A mixture of acetone (1000 mg, 17.24 mmol) and NaH (1373 mg, 34.48 mmol) was stirred with ethyl acrylate (3965 mg, 39.65 mmol) at –10 °C for 5 min under nitrogen atmosphere. Progress of the reaction was monitored by TLC. On completion of the reaction, the reaction mixture was acidified with 1 M HCl, extracted with EtOAc (3 × 5 mL) and washed with brine. The combined organic layers were dried over anhyd Na2SO4 and concentrated under reduced pressure. Silica gel column chromatographic purification (EtOAc–hexane, 7:3) of the crude mixture afforded 1 as a light yellow gummy liquid (2412 mg, 66% yield) along with 2 as a light yellow solid (77 mg, 4%) and 3 as a light yellow liquid (176 mg, 7%). IR (KBr): 1729, 1598, 1455, 1198, 1092, 1031, 851 cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.21 (t, J = 7.1 Hz, 6 H), 1.68–1.75 (m, 4 H), 2.00–2.09 (m, 4 H), 2.28–2.58 (m, 10 H), 3.38–3.47 (m, 2 H), 4.04–4.12 (m, 4 H), 5.40 (s, 1 H), 6.67 (br, 1 H). 13C NMR (75 MHz, CDCl3): δ = 14.07, 24.26, 24.56, 25.41, 26.19, 29.76, 31.43, 31.94, 39.64, 41.27, 48.25, 58.26, 60.50, 104.01, 173.23, 173.67, 187.73, 195.15, 203.79, 204.06. HRMS (EI): m/z [M + H] calcd for C11H17O4: 213.2503; found: 213.2519