48 石 油 学 会 誌 Sekiyu Gakkaishi, 38, (1), 48-51 (1995)

[Note] Synthesis of Glutaconic Acid Salt from Cesium 3-Butenoate with Carbon Dioxide

Kiyoshi KUDO*, Futoshi IKOMA, Sadayuki MORI, and Nobuyuki SUGITA

Institute for Chemical Research, Kyoto University, Gokanosho, Uji, Kyoto 611

(Received July 13, 1994)

Cesium carbonate (Cs2CO3) is an effective catalyst used for the carboxylation of cesium 3-butenoate (1) with carbon dioxide, in dimethylformamide, affording cesium glutaconate (2) in good yields (-55%) at temperature of 100℃ and pressure of 42atm. The reaction is restricted to 1-Cs2CO3 system. It is essential to use more than unity of the Ce2CO3/1 ratio to attain high yield. Other system such as potassium 3-butenoate-K2CO3 system is inactive. The effects of the pressure of CO2, reaction tem- perature and the amount of Cs2CO3 on the yield of carboxylated product were examined.

1. Introduction

(1) The chemical utilization of CO2, as a resource for the production of useful substances, has been Although we have explored the subject of whether rather limited. It has been well established that or not this carboxylation could be applicable to the alkali metal phenolates are required as catalysts in synthesis of olefinic dicarboxylic acids by the a number of carboxylation reactions of active carboxylation of olefinic monocarboxylic acid salts, hydrogen compounds. Theoretical and funda- it was found that this procedure could not be mental studies on this carboxylation were reported employed because most of the starting acids or by Bottaccio et al.1) and Kwan et al.2). In these resulting acids were easily decomposed. The carboxylations, CO2 is activated, presumably, by ploblem was solved by use of cesium carbonate chelation to the alkali metal moiety of phenolate3). (Cs2CO3)and cesium salt in DMF solution. Glutaconic acid or its derivatives are important The purpose of this paper is to report on the facile intermediates for synthesis of the antibiotics4). and regioselective carboxylation of the tautomeric Battaccio and co-workers1) have reported, using a acid salt, cesium 3-butenoate (1), with CO2, using model reaction of alkali metal phenolate-promoted Cs2CO3as a base, which provided a useful method for carboxylation, that methyl 3-butenoate and methyl the synthesis of glutaconic acid salt (2) under mild crotonate are carboxylated to form monomethyl conditions; i.e., under pressure of 50atm of CO2 at glutaconate, along with monomethyl ethylidene- temperature of 100℃ (Eq. (2)) malonate, in hexamethyl-phosphoramide solution at temperature of 25℃, under atmospheric pressure. The yield, however, was low(15%), and the develop- 2. Experimental ment of efficient procedure was required. Previously, the authors has reported that anhy- 2.1. Material drous potassium acetate reacts with CO2 in the Commercially available solvent, dimethylform- presence of anhydrous potassium carbonate to give amide (DMF), was distilled before use. Alkali potassium malonate, under extreme conditions metal salts of olefinic monocarboxylic acid were (Eq. (1))5). prepared by neutralization with required amounts of aqueous alkali metal hydroxides. The solu- tions were, then, evaporated to dryness and further

(2)

石 油 学 会 誌 Sekiyu Gakkaishi, Vol. 38, No. 1, 1995 49

dried in vacuum (ca. 5mmHg) at 150-180℃. Table 2 Carboxylation of Cesium 3-Butenoate under Alkali phenoxides were prepared in accordance Various Conditionsa) with the previous report3). Alkali metal car- bonates, obtained commercially, were used after being further dried. 2.2. Procedure A typical procedure carried out follows: A mixture of 1 (2mmol), Cs2CO3 (3mmol), and solvent DMF (10ml) were charged into a shaking- type autoclave (ca. 30ml). Air was flushed out with CO2, after which a desired amount of liquid a) Substrate, 2mmol; DMF, 10ml; time, 3h. b) Based on 1 CO2 was charged into the autoclave, at room employed. c) (Yield of 2/Conversion)×100. temperature. The autoclave was then heated and shaken constantly at 100℃ for 3h. In general, the carbonate is utilized in slurry form, regardless of solvent. The reaction mixture was cooled and those investigated, cesium carbonate was the most then poured into water (50ml) and acidified with effective base (Run 2), while potassium carbonate, dilute perchloric acid, and then determined by potassium phenoxide, and organic bases e.g. HPLC (Shimadzu LC-10A). Column, Shim- DBU or tributylamine, were less effective (Runs 3- pack SCR-101H, (0.25m×6mm), eluted with 7). This is particularly notable in that the aqueous perchloric acid (pH 2.1) solution, was corresponding reaction of 1, using cesium phen- used. oxides, give only low yield of 2, attributed to easy tautomerization of 1 (Run 5). An alkali metal 3. Results and Discussion species of the substrate had also significant effect on the reactivity, namely, the carboxylation of The reaction conditions, leading to the for- potassium salt led to a noticeable decrease of the mation of 2, was initially examined, using various yield in 2 (Runs 8 and 9). When methyl 3- bases, which show the sensitivity of this reaction to butenoate was used in place of salt (1), the reaction the nature of added base are shown in Table 1. In did not afford, at all, the corresponding diacid the reaction, solvent DMF was used, because DMF monoester. These results suggest that both alkali have higher solubilities for 1 (0.3mol/l) and metals of carbonate and salt (1) affect reactivity. Cs2CO3 (7mmol/l) than other solvents investigat- Next, the effects of reaction variables on the ed. product yield and selectivity (Table 2) were In the absence of base, only trace amounts of 2 surveyed. The yield of 2 was increased with the was formed, but greater amount of 3 (75%) resulted amount of cesium carbonate, up to about the from the tautomerization of 1(Run 1). Key to the equivalent of the substrate, while excess amount of successful formation of 2 rests on the choice of the cesium carbonate caused little or no increase in the base. The appropriate base must not only be product (Runs 10-13). It is noteworthy that the capable of driving the carbanion formation, but tautomerization of 1 into 3 decreased with an also capable of trapping α-hydrogen. Among all increase in the amount of the carbonate, and a considerable amount of cesium hydrogencarbon- ate (CsHCO3) was always observed. These facts suggest that the cesium carbonate do not operate as Table 1 Carboxylation of Alkali Metal 3-Butenoate with a base nor as an effective proton acceptor. The Various Systemsa) reaction was possible with CO2 at pressures rang- ing from 10 to 100atm. The yield and selectivity of 2 increased with the initial increase in the pressure, but nearly leveled off as the pressure increased to ca. 40atm (Runs 12, 14 and 15). The reaction temperature was also an important factor. The reaction did not occur at temperatures below 70℃ (Run 16). At higher temperature, the tau- tomer 3 increased at the expense of production 2 (Run 17). The best result, with respect to the a) Substrate, 2mmol; Base, 3mmol; DMF, 10ml; CO2: 100atm, 100℃, 3h. b) Based on 1 employed. c) 1,8- yield and selectivity of the desired product (2), was Diazabicyclo[5.4.0]undec-7-ene. achieved by the reaction carried out with CO2 at

石 油 学 会 誌 Sekiyu Gakkaishi, Vol. 38, No. 1, 1995 50

Scheme 1

pressures ranging from about 40 to 50atm, and at is abstracted by cesium carbonate as CsHCO3 in temperature of 100℃ (Run 15). The reaction was competition with its transfer onto γ-carbon, and complete within a lapse of about 3h. the resultant carbanion (1b) may then react with It is interesting to note that the carboxylation is CO2 to form 2 as shown in Scheme 1. regioselective, and the addition of CO2 took place The high reactivity of cesium carbonate for mainly at the γ-carbon of the acid(1) leading to 2. carboxylation may be ascribed to the strong Reaction products at both α- and β-carbon, such as electron-donating property of cesium metal, which ethylidenemalonic acid or methylenesuccinic acid, enhances the nucleophilicity of the dissociated were not obtained at all. carbonate anion (CsCO3-) to capture proton from The present carboxylation is characteristic of 1a. substrate 1. Other olefinic acids such as cesium salts of acrylic acid, crotonic acid and 3- and 4- References pentenoic acid did not afford the corresponding products, and these substrates were recovered 1) Bottaccio, G., Chiusoli, G. P., Felicioli, M. G., Gazz. Chim. unchanged. These results, thus, strongly suggest Ital., 103 (1-2), 105 (1973). that an intermediate (1a), generated in the 2) Mori, H., Yamamoto, H., Kwan, T., Chem. Pharm. Bull., 20, 2440 (1972). prototropic equilibrium between the two triads 1 3) Hales, J. L., Jones, J. I., Lindsey, A. S., J. Chem. Soc., 1954, and 3, which lies so far to the right, play an 3145. important role and causes the effective carbox- 4) Perri, S. T., Slater, S. C., Toske, S. G., White, J. D., J. Org. ylation under mild conditions. Chem., 55, 6037 (1990). Although detailed mechanism of the reaction is 5) Kudo, K., Takezaki, Y., Kogyo Kagaku Zasshi, 70, 2147 not known, it is apparent that an α-hydrogen of 1 (1967).

石 油 学 会 誌 Sekiyu Gakkaishi, Vol. 38, No. 1, 1995 51

要 旨

3-ブ テ ン酸セ シウム からの二酸化炭 素によ るグル タコン酸 塩の合成

工藤 清, 生駒 太志, 森 貞之, 杉 田信之

京都大学化学研究所, 611京 都府宇治市五ヶ庄

炭 酸 セ シ ウ ム は (Cs2CO3), DMF溶 液 中, 3-ブ テ ン酸 セ シ 比 を1以 上 で 行 う こ と が必 要 で あ る。 この 反 応 は 他 の ア ル カ ウム (1) の 二 酸 化 炭 素 に よ る カ ル ボ キ シ ル化 反応 に高 い触 媒 リ塩 系, た とえ ば3-ブ テ ン酸 カ リ ウム-炭 酸 カ リ ウム 系 で は 進 活 性 を示 し, 100℃, 42気 圧 で, グ ル タ コ ン酸 塩 (2) が 高 収 行 し ない。 セ シ ウ ム塩1-炭 酸 セ シ ウ ム系 で の 生 成 物 収 率 に 及 率 (～55%) で得 られ た。 この 反 応 は セ シ ウ ム塩1-炭 酸 セ シ ぼ す圧 力, 温 度, お よび炭 酸 塩 の添 加 量 な ど の影 響 を検 討 した。 ウ ム系 に特 異 的 で あ り, 2を 高 収 率 で 得 る た め に はCs2CO3/1

Keywords Carbon dioxide, Carboxylic acid, Carboxylation, Cesium carbonate, Cesium 3-butenoate

石 油 学 会 誌 Sekiyu Gakkaishi, Vol. 38, No. 1, 1995