N-포밀 아스파르테임의 산화탈포밀 반응에 의한 아스파르테임의 제조방법

박동현; 이윤식

Journal of the Korean Industrial and Engineering Chemistry, Vol.1, No.1, 91-99, October, 1990

Export Citation

N-포밀 아스파르테임의 산화탈포밀 반응에 의한 아스파르테임의 제조방법

Synthetic Method of Aspartame via Oxidative Deformylation of N-Formyl Aspartame

박동현, 이윤식

초록

For-α-APM을 For-Asp anhydride와 Phe-OMe를 MEK, CH₃CN, 물 등의 용매를 사용하여 반응시켜 효율적으로 합성하였다. For-α-APM과 For-β-APM의 혼합물로부터 순수한 For-α-APM의 회수는 pH 4.00에서의 연속적인 분별추출로 분리 수거가 가능하였다. H₂O₂ 공급원으로 H₂O₂/THF, 과탄산소다, H₂O₂/HCl/MeOH등의 다양한 산화계를 사용하여, H₂O₂에 의한 산화방법으로 탈포밀반응을 성공적으로 수행하여 높은 수율로 아스파르테임을 얻을 수 있었다. 이 때 HCl이나 TsOH와 같은 산이 H₂O₂의 분해를 억제시키고 산화능을 증대시킴으로써 탈포밀 반응의 효율을 높일 수 있었다.

For-α-APM was efficiently prepared by the reaction of For-Asp anhydride and Phe-OMe in methylethylketone, CH₃CN, and in water. The selective recovery of For-α-APM from the resulting For-α-APM and For-β-APM mixture was possible via repetitive extraction at constant pH of 4.00. The oxidative deformylation was successfully performed by using several oxidants including H₂O₂/THF, sodium percarbonate, and H₂O₂/HCl/MeOH giving APM in high yields. The efficiency of the oxidative deformylation was raised in acidic condition for all the deformylation reactions.

[References]

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Japan Kokai, 51-13737 (1976)
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Sheehan JC, Yang DDH, J. Am. Chem. Soc., 80, 1154 (1958)
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Park B, Ind. Eng. Chem. Anal. Ed., 3, 77 (1931)
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[1] Mazur RH, Schlatter JM, Goldkamp AA, J. Am. Chem. Soc., 91, 2684 (1966)

[2] Lee YS, SNU Eng. Report, 17, 313 (1985)

[3] Japan Kokai, 48-18249 (1973)

[4] Japan Kokai, 48-61451 (1973)

[5] Japan Kokai, 48-76835 (1973)

[6] Japan Kokai, 49-14217 (1974)

[7] Japan Kokai, 50-58025 (1975)

[8] Japan Kokai, 51-13737 (1976)

[9] Japan Kokai, 51-113841 (1976)

[10] Japan Kokai, 55-167267 (1980)

[11] Ger. off., 2,107,411 (1971)

[12] U.S. Patent, 3,879,372 (1975)

[13] U.S. Patent, 3,948,971 (1976)

[14] European Patent, Appl., 0,048,051 (1981)

[15] Sheehan JC, Yang DDH, J. Am. Chem. Soc., 80, 1154 (1958)

[16] U.S. Patent, 1,243,169 (1971)

[17] Ger. Off., 2,635,948 (1977)

[18] 대한민국 특허공보 82-2080 (1982)

[19] Geiger R, Siedel W, Chem. Ber., 101, 3386 (1986)

[20] Ger. off., 2,554,421 (1976)

[21] Losse G, Nadolski D, J. Prak. Chem., 4(24), 118 (1964)

[22] Losse G, Zonnchen W, Chem. Ber., 636, 140 (1960)

[23] Losse G, Z. Chem., 5(6), 225 (1965)

[24] Japan Kokai, 51-39602 (1976)

[25] Ando W, Chem. Lett., 664 (1986)

[26] European Patent, 0,058,063 (1982)

[27] U.S. Patent, 4,071,511 (1978)

[28] U.S. Patent, 4,173,562 (1979)

[29] Isowa Y, Ohmori M, Ichikawa T, Mori K, Tetrahedron Lett., 28, 2611 (1979)

[30] Park B, Ind. Eng. Chem. Anal. Ed., 3, 77 (1931)

[31] Duke FR, Haas TW, J. Am. Chem. Soc., 65, 704 (1960)

[32] Funatsu G, Biochemistry, 3, 1351 (1964)

[33] Bier M, "Electrophoresis," Academic Press, New York, Vol. 1 (1959)

[34] Perrin DD, Armarego WLF, Perrin DR, "Purification of Laboratory Chemicals," 2nd ed., Oxford, Pergamon Press (1980)

[35] Ariyoshi Y, Yamatini T, Uchiyama N, Bull. Chem. Soc. Jpn., 46, 1893 (1973)