Biology
J. of Advanced Engineering and Technology Vol. 2, No. 2 (2009) pp. 281-283
Synthesis of 2-Acetylcyclohexanone Using Pyrrolidine-enamine
Eun-SunYoo
Department of Oriental Medicine Industry, Honam University, Korea
(Received : May. 20, 2009, Revised : Jun. 02, 2009, Accepted : Jun. 12, 2009)
Abstract : 2-Acetylcyclohexanone was synthesized by acylation reaction of acidic anhydride using enamine as organiocatalyst instead of a strong base, NaOH, resulting in milder reaction conditions. The reaction was conducted in toluene and direct distillation of the reaction mixture before hydrolysis was leaded to a high yield of the pyrrolidine enamine. This condition was leaded good yields (73.6%) without side reactions. Acylation gave an enol form (71.7%) and a keto form (28.3%) of 2-acetylcyclohexanone mixture, the composition of which was determined by 1H-NMR spectroscopy. Key words : pyrrolidine, enamine, mild condition, NMR
1. Introduction
The formation reactions of carbon-carbon bonds are important in organic synthesis [1-5]. In general, acylation reaction is one of the important carbon-carbon forming reactions. It belongs to the reactions of the enolate derived from a carbonyl group with an electrophilic carbon such as Aldol, Claisen, Michael reaction and alkylation of metal enolates [6-9].The acylation reaction as well as above other reactions of enolates has serious limitations to be overcome. In these reactions, a strong base NaOH is needed to transform the carbonyl compounds into their anion forms. Generally, the carbonyl compounds such as ketone and aldehyde have high pKa values (pKa ~ 20) [1]. It is difficult to make their − anion forms of carbonyl compounds by removing the hydrogens on the α-carbons because of their weakly acidic characteristics. Therefore, the product yields of acylation, alkylation, and an aldol condensation are low and unwanted side reactions occur (Figure 1). In order to avoid side reactions, a good nucleophile needs to be produced
Synthesis of 2-Acetylcyclohexanone Using Pyrrolidine-enamine
Eun-SunYoo
Department of Oriental Medicine Industry, Honam University, Korea
(Received : May. 20, 2009, Revised : Jun. 02, 2009, Accepted : Jun. 12, 2009)
Abstract : 2-Acetylcyclohexanone was synthesized by acylation reaction of acidic anhydride using enamine as organiocatalyst instead of a strong base, NaOH, resulting in milder reaction conditions. The reaction was conducted in toluene and direct distillation of the reaction mixture before hydrolysis was leaded to a high yield of the pyrrolidine enamine. This condition was leaded good yields (73.6%) without side reactions. Acylation gave an enol form (71.7%) and a keto form (28.3%) of 2-acetylcyclohexanone mixture, the composition of which was determined by 1H-NMR spectroscopy. Key words : pyrrolidine, enamine, mild condition, NMR
1. Introduction
The formation reactions of carbon-carbon bonds are important in organic synthesis [1-5]. In general, acylation reaction is one of the important carbon-carbon forming reactions. It belongs to the reactions of the enolate derived from a carbonyl group with an electrophilic carbon such as Aldol, Claisen, Michael reaction and alkylation of metal enolates [6-9].The acylation reaction as well as above other reactions of enolates has serious limitations to be overcome. In these reactions, a strong base NaOH is needed to transform the carbonyl compounds into their anion forms. Generally, the carbonyl compounds such as ketone and aldehyde have high pKa values (pKa ~ 20) [1]. It is difficult to make their − anion forms of carbonyl compounds by removing the hydrogens on the α-carbons because of their weakly acidic characteristics. Therefore, the product yields of acylation, alkylation, and an aldol condensation are low and unwanted side reactions occur (Figure 1). In order to avoid side reactions, a good nucleophile needs to be produced
References: (1) Pavia, D,L., Lampman, G. M., Kriz, G.S. and Engel, R.G. Intoduction to Organic Laboratory Techniques: A Small Scale Approach, 2nd ed. Thomson Brooks/Cole: Canada, 330-339 (2005). (2) Stork, G., Brizzolara, H., Landesman, H., Szmuszkovicz, J. and Terrell, R. J. Am Chem. Soc., 85 (2), 207-222 (1963). (3) Cook, A.G., Absi, M.L. and Bowden, V.K. J. Org. Chem., 60(10), 3169-3171 (1995). (4) Cao, C., Sun, X., Zhou, J. and Tang, Y. J. Org. Chem., 72(11), 4073-4076 (2007). (5) Meyer, W.L., Bramon, M. J., Burgos, C, Goodwin, T. and Howard, R.W. J. Org. Chem., 50(4), 438-447 (1985). (6) Luo, S., Xu, H., Mi, X., Li, J., Zheng, X. and Cheng, J. J. Org. Chem., 71, 9244-9247 (2006). (7) Curphey, T.J., Hung, J.C. and Chu, C.C. J. Org. Chem., 40, 607614 (1975). (8) Bruson, H.A. and Riener, T.W. J. Am. Chem. Soc., 64, 2850-2856 (1942). (9) Curphey, T., Hung, C.Y. and Chu, C.C. J. Org. Chem., 40(5), 607-614 (1975). (10) Chiba, T., Okimoto, M., Nagai, H. and Takata, Y. J. Org. Chem., 44(20), 3519-3523 (1979). (11) Iglesias, E. J. Org. Chem., 68(7), 2680-2688 (2003). 3.3 cm (0.3×11 protons) of the 4.6 cm intergral height was assigned to the enol structure. Enol % = 3.3/4.6 × 100 = 71.7%, Keto % = (4.6-3.3)/4.6 × 100 = 28.3%. The enol structure was the major form of 2-acetylcyclohexanone, same as the Pavia et al [1] and Igiesias [11]. The reason for obtaining more enol form (71.7 %) than keto form (28.3 %) of 2-acetylcyclohexanone can be explained that the enol form is stabilized by conjugation and intramolecular hydrogen bonding as shown in Figure 4. The C = C bond of the enol form decreases the electron density of π bonds through conjugation. The H …O hydrogen bond also stabilizes the enol form by forming a ring. 4. Conclusion In conclusion, using an enamine, 2-acetylcyclohexanone was synthesized by acylation reaction of acidic anhydride. This reaction carried out mild reaction conditions using an enamine instead of NaOH in order to bond to the ketone with good yields (73.6%) J. of Adv. Eng. and Tech., Vol. 2, No. 2 (2009)