Fast Aldol-Tishchenko Reactions Utilizing 1,3-Diol Monoalcoholates as the Catalysts

The aldol-Tishchenko reaction of enolizable aldehydes is a simple and effective way to prepare 1,3-diol monoesters, which are widely used as coalescing agents in the paint industry. The use of monoalcoholates of 1,3-diols as catalysts gives fast and clean reactions compared with the previous use of several inorganic catalysts. The use of the proper 1,3-diol moiety in the catalyst also reduces the amount of side products which are due to ester interchange between product esters and the catalyst. The rapid water-free method developed herein allows fast preparation of monoesters with excellent yield and minimized formation of side products. Introduction In many cases traditional Tishchenko1 and aldol-Tishchenko2 reactions are competitive with each other.3 However, these reactions can sometimes proceed selectively with the proper choice of catalyst. The aldol-Tishchenko reaction usually requires a basic metal hydroxide catalyst which can activate both aldol reaction and Tishchenko esterification.4 Some other catalysts have also been used such as metal alkoxides of monofunctional alcohols,5,6 LiWO2, Cp*2Sm(thf)2, polynuclear carbonyl ferrates,9 and simple metal hydroxides.10 Traditional Tishchenko esterification is usually activated in the presence of Lewis acidic catalysts such as aluminum alcoholates.11 In a typical aldol-Tishchenko reaction (Scheme 1), an aldol reaction of the easily enolizable aldehyde first takes place, and the product forms a hemiacetal-like 1,3-dioxan-4-ol 4 (also called aldoxan at this case) with the free aldehyde.12 Dioxanol 4 reacts to give the diol monoester 5 via a Tishchenko reaction in which an intramolecular hydride shift takes place.13 In the presence of the catalyst, for example, Ca(OH)2, and with heating, the balance between monoesters 5 and 6 is slowly converted to the more stable monoester 6 having a secondary alcohol group instead of a primary one as in 5.2 This aldol-Tishchenko reaction is very closely related to the Evans-Tishchenko reaction in which â-hydroxyketones react with a free aldehyde to give a glycol monoester with excellent anti-selectivity.14 In our previous work we have studied the chemistry of 1,3-dioxan-4-ols and their behaviour in the Tishchenko reaction. It is well-known that several metal hydroxides destroy esters by hydrolysis and thereby reduce the yield. We started to search for substitute catalysts and found that diol monoalcoholates solve this problem.15 Herein we wish to report the results of our studies on the homogeneous aldolTishchenko reaction, wherein we have achieved fast reactions from enolizable aldehyde 1 to monoesters 5 and 6 with (1) Tishchenko, W. J. Russ. Phys.-Chem. Soc. 1906, 38, 355. Lin, I.; Day, A. J. Am. Chem. Soc. 1952, 74, 5133-5135. (2) Fouquet, G.; Merger, F.; Platz, R. Liebigs Ann. Chem. 1979, 1591-1601. (3) Villani, F.; Nord, F. J. Am. Chem. Soc. 1947, 69, 2605-2607. Tsuji, H.; Yagi, F.; Hattori, H.; Kita, H. J. Catal. 1994, 148, 759-770. (4) Schwenk, U.; Becker, A. Liebigs Ann. Chem. 1972, 756, 162-169. (5) Villani, F. J.; Nord, F. F. J. Am. Chem. Soc. 1947, 69, 2605-2607. Kuplinski, M. S.; Nord, F. F. J. Org. Chem. 1943, 8, 256-270. (6) Ito, K.; Kamiyama, N.; Nakanishi, S.; Otsuji, Y. Chem. Lett. 1983, 657670. (7) Villacorta, G. M.; San Filippo, J., Jr. J. Org. Chem. 1983, 48, 8 (8), 11511154. (8) Miyano, A.; Tashiro, D.; Kawasaki, Y. Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 1998, 39, 6901-6902. (9) Ito, K.; Kamiyama, N.; Nakanishi, S.; Otsuji, I. Chem. Lett. 1983, 657660. (10) McCain, J. H.; Theiling, L. F. (Union Carbide Corp.). U.S. Patent 3,718,689, 1973; Chem. Abstr. 1973, 78, P135694k. For aldol of isobutyraldehyde see also: Hagemeyer, H. J., Jr.; Lonhview, T. (Eastman-Kodak Co.). U.S. Patent 2,829,169, 1958; Chem. Abstr. 1958, 52, P12897b. (11) Ooi, T.; Miura, T.; Takaya, K.; Maruoka, K. Tetrahedron Lett. 1999, 40, 7695-7698. Ogata, Y.; Kawasaki, A. Tetrahedron 1969, 25, 929-935. Saegusa, T.; Ueshima, T. J. Org. Chem. 1968, 33, 3 (8), 3310-3312. Ogata, Y.; Kawasaki, A.; Kishi, I. Tetrahedron 1967, 23, 825-830. (12) Kirk, R. E.; Othmer, D. F. Encyclopedia of Chemical Technology, 3rd ed.; Wiley-Interscience: New York, 1984; Vol. 4, p 379. Späth, E.; Lorenz, R.; Freud, E. Ber. Dtsch. Chem. Ges. 1943, 76 (12), 1196-1208. (13) Loog, O.; Mäeorg, U. Tetrahedron Asymmetry 1999, 10, 2411-2415. AbuHasanayn, F.; Streitwieser, A. J. Org. Chem. 1998, 63, 2954-2960. (14) Lu, L.; Chang, H.-Y.; Fang, J.-M. J. Org. Chem. 1999, 64, 843-853. Evans, D. A.; Hoveyda, A. M. J. Am. Chem. Soc. 1990, 112, 6447-6449. (15) Törmäkangas, O. P.; Koskinen, A. M. P. Tetrahedron Lett. 2001, 42, 27432746. Scheme 1. Aldol-Tishchenko reaction of enolizable aldehydes Author's accepted manuscript, published in Organic Process Research & Development 5 (2001) 421−425 excellent yields. This work was focused on converting isobutyraldehyde 7 to diol monoesters 9 and 10 which are the most common coalescing agents, for example, for latex paints. Consumption of 7 to condensation and esterification products was 260 million pounds in 1997 exclusively in the U.S.16 Results and Discussion To our knowledge, this is the first time that monoalcoholates of 1,3-diols have been studied as catalysts for aldolTishchenko reactions. The use of sodium alcoholates of monofunctional alcohols has been reported, but in this case the yield of monoesters of the diol was reduced due to ester interchange between the catalyst and the product ester.17 The effect of the catalyst on the reaction rate was found to be crucial in our experiments, giving a reaction several times faster than that obtained with the metal hydroxides traditionally used. This is partly due to the completely homogeneous reaction system. In some industrial processes the use of metal hydroxides can require the presence of some water which can create quantities of wastewater and thus extra costs.18 Another considerable disadvantage with metal hydroxide catalysts is the fast and irreversible hydrolysis of the product esters. In our procedure, water-free reaction conditions are used, and after the reaction and short workup, the solvent and products can be easily separated by means of fractional distillation. However, rather fast ester interchange between the catalyst and the product ester can still cause slight loss in the yield. This can be avoided by choosing a suitable 1,3diol as the catalyst. We have here studied the role of different alkali metals in the catalyst and optimized the reaction conditions for this process. In our previous experiments we used the monolithium alcoholate of 2,2-dimethylpropan-1,3diol (neopentyl glycol; later NPG) 8 as the catalyst in the Tishchenko esterification of 1,3-dioxan-4-ol derivatives.15 In the first experiment of this paper, it was figured out how unavoidable the ester interchange between the catalyst and the product is. The same Li-NPG catalyst 8 (30 mol %) was used here in the case of the aldol-Tishchenko reaction. Isobutyraldehyde 7 (RdR′dCH3 in Scheme 1) was used as the starting material and added directly into the catalyst solution (0.5 M in THF, 30 mol %). At room temperature, the reaction was found to be suprisingly fast. The desired products were the glycol monoesters (2,2dimethyl-3-hydroxyl-1-isopropyl-propyl)-2-methylpropionate 9 and (3-hydroxy-2,2,4-trimethylpentyl)-2-methylpropionate 10. Formation of NPG-monoisobutyrate 11 and 2,2,4trimethylpentan-1,3-diol 12 were observed after only 15 min, proving that there was fast ester interchange between products (9 and 10) and the catalyst 8 (Scheme 2). In later experiments, we decided to use monoalcoholates prepared from diol 12 as the catalysts to avoid the formation of side products related to monoester 11. The catalysts used in the experiments are shown in Scheme 3. Catalysts 13, 14, and 15 were prepared in a straightforward fashion by adding a solution of 12 in THF (or hexanes) into the hydride slurry at 0 °C under argon. When BuLi (13) or Et2Zn (16) were used, these were added directly into the precooled THF or hexane solution of diol 12. The catalyst solution was stirred for 60 min at 0 °C before use. In the experiment series, freshly distilled isobutyraldehyde 7 (4.50 g, 50 mmol) was fed over 2 min into the reaction containing the catalyst solution, giving an exothermic reaction (Scheme 4). The amount of catalyst used was always 1 mol % except entry 5 (30 mol %) in which case ester interchange with a bulky catalyst was studied. In all entries of Table 1 the temperature was kept stable at +55 °C ((3 °C) with external cooling and heating at the very end of the reaction. After a reaction time of 30 min the reaction was (16) Oxo Chemicals: Isobutyraldehyde. In Chemical Economics Handbook; Stanford Research Institute: International, Menlo Park, California, November, 2000. (17) Hagemeyer, H. J., Jr.; Wright, H. N., Jr. (Eastman Kodak Co.). U.S. Patent 3,091,632, 1963; Chem. Abstr. 1963, 59, P13828g. (18) Perry, M. A.; Hagemeyer, H. J., Jr. (Eastman Kodak Co.). U.S. Patent 3,291,821, 1966; Chem. Abstr. 1967, 66, P37420a. Scheme 2 Scheme 3. The catalysts related to diol 12 used in experiments