Sodium Hydrogensulfite를 이용한 환원반응에서 2-Hydroxyphenyl Diazonium 유도체의 입체장애에 관한 연구

권오준; 김지언; 박세민; 김근식; 윤순도; O-Zoon Kwon; Jieun Kim; Se-Min Park; Keun-Sik Kim; Soon-Do Yoon

Applied Chemistry for Engineering, Vol.30, No.4, 509-5011, August, 2019

DOI10.14478/ace.2019.1054 Export Citation

Sodium Hydrogensulfite를 이용한 환원반응에서 2-Hydroxyphenyl Diazonium 유도체의 입체장애에 관한 연구

Effects of Steric Hindrance of 2-Hydroxyphenyl Diazonium Derivatives in the Reductive Reaction by Using Sodium Hydrogensulfite

권오준, 김지언, 박세민, 김근식, 윤순도^{1, †}

케이에스랩(주)
¹전남대학교 공학대학 화공생명공학과

O-Zoon Kwon, Jieun Kim, Se-Min Park, Keun-Sik Kim, and Soon-Do Yoon^{1, †}

Knowledge Industry Center #303, Jeonnam Thechno-Park, Yulchonsandan 4-ro 13, Haeryong-myeon, Suncheon-si, Jeonnnam 58034, South Korea
¹Department of Chemical and Biomolecular Engineering, Chonnam National University, Yeosu 59626, Republic of Korea

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초록

정밀화학 및 의약품, 화장품에 사용되는 hydrazine 유도체는 diazonium salt로부터 환원반응을 통해 합성할 수 있다. SnCl2를 이용한 환원방법은 반응 전환이 용이하나 반응 후 최종 제품에 중금속 잔류문제가 민감한 경우 사용에 제한을 받는다. 중금속이 없는 라말린(Ramalin)을 제조하기 위해 NaHSO3를 이용한 환원방법을 개발하였으며, 이때 보호된 (2-hydoxyphenyl)diazonium 유도체의 diazonium 그룹을 hydrazine 그룹으로 전환하기 위한 환원반응에서, 하이드록시 그룹의 보호기 크기에 따른 입체장애 영향을 확인하였고, 보호기의 크기는 C1~C5 직쇄형 보호기가 바람직하였다. 라말린 제조를 위한 경제성과 공업적 생산을 고려하여 다양한 보호기를 검토한 결과, 비교적 안정한 조건에서 탈보호할 수 있는 알릴 그룹을 사용할 경우 2-(allyloxy)aniline으로부터 (2-allyloxyphenyl)hydrazine를 수율 85%, 순도 99.7%로 가장 좋은 결과를 얻을 수 있었다.

Hydrazine derivatives used in fine chemicals, pharmaceuticals and cosmetics can be synthesized by reduction reaction from diazonium derivatives. The reduction method using SnCl2 facilitates the reaction conversion, but the use of SnCl2 is limited when residual heavy metals are issued in the final product. For the conversion of protected (2-hydroxyphenyl)diazonium derivatives into its hydrazine derivatives in Ramalin preparation process, the reduction method was developed by using NaHSO3. In this study, the effect of steric hindrance according to the protected 2-hydroxygroupinphenyldiazonium derivatives was found, and linear C1~C5 alkyl groups for the hydroxy protection were preferable during the diazonium reduction reaction. Considering the economical efficiency and industrial production for the preparation of Ramalin, a variety of protecting groups were investigated. As a result, 2-(allyloxyphenyl)hydrazine was obtained with 85% yield and 99.7% purity when the hydroxy protecting group was used as an allyl group that could be easily deprotected.

Keywords:Hydrazine;Reduction;Diazonium;Sodium sulfite;Ramalin

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[1] Robinson B, Chem. Rev., 63(4), 373 (1963)

[2] (a) Barton SD, Ollis WD, Sutherland IO, The Synthesis and reactions of Organic Compounds: Volume 2, Nitrogen Compounds, Carboxylic Acids, Phoshorus Compounds, pp. 154-159, Pergamon, Oxford (1979), (b) Zollinger H, Chemistry D. Aromatic I, Heteroaromatic Compounds, VCS (1994), (c) Patai S (ed.), The Chemistry of Diazonium and Diazo Groups, Wiley, New York (1978).

[3] Browne DL, Baxendale IR, Ley SV, Tetrahedron, 67, 10296 (2011)

[4] Vidyarthi SN, Kumar D, Singh R, Tiwari S, Asian J. Chem., 20(5), 3828 (2008)

[5] Yim JH, Kim IC, Lee SG, Kim DK, Method for preparing ramalin, US Patent 8,865,934B2 (2014).

[6] Wang R, Xu J, Selective alkylation of aminophenols, ARKIVOC, 9, 293-299 (2010).

[7] Yu Z, Tong G, Xie X, Zhou P, Lu Y, Su W, Org. Process Res. Dev., 19(7), 892 (2015)