International Journal of

ADVANCED AND APPLIED SCIENCES

EISSN: 2313-3724, Print ISSN: 2313-626X

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 Volume 10, Issue 11 (November 2023), Pages: 190-201

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 Original Research Paper

An elementary study of the industrialized preparation of 1,1-difluoro acetone: Starting material of fluoropyrazole succinate dehydrogenase inhibitor

 Author(s): 

 WeiKang Lin 1, *, Puivun Chai 1, Lei Cao 2, Le Kang 3, Xiaoming Jiang 4

 Affiliation(s):

 1Department of Chemical and Petroleum Engineering, Faculty of Engineering Technology and Built Environment, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia
 2Department of Oncology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, 223800 Suqian, Jiangsu, China
 3School of Pharmacy, Henan University of Chinese Medicine, 450046 Zhengzhou, Henan, China
 4Department of Research and Development, Zhejiang Yuntao Biotechnology Co., Ltd., 312369 Shaoxiang, Zhejiang, China

 Full text

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 * Corresponding Author. 

  Corresponding author's ORCID profile: https://orcid.org/0000-0003-2960-6447

 Digital Object Identifier (DOI)

 https://doi.org/10.21833/ijaas.2023.11.024

 Abstract

In recent years, the development and increasing market presence of fungicides incorporating a fluoropyrazole ring, recognized as succinate dehydrogenase inhibitor fungicides, has gained momentum. The fluoropyrazole ring stands as the foundational nucleus of these fungicides, with its production cost being a pivotal concern for chemical industries. Significantly, the cost of 1,1-difluoro acetone largely influences this manufacturing cost. A cost-effective availability of 1,1-difluoro acetone could revolutionize the current methodologies for fluoropyrazole ring synthesis, primarily due to its enhanced safety and environmental sustainability. This study introduces an industrialized production methodology for 1,1-difluoro acetone, underlining its economic efficiency. Originating from ethyl acetoacetate, dibromide is synthesized in n-heptanol through the Oxone/KBr system. Following a fluorine-bromine exchange reaction with potassium fluoride, difluoride is obtained. Subsequent hydrolysis of the difluoride using 50% sulfuric acid leads to the formation of 1,1-difluoro acetone. Notably, while bromination and fluorination stages employ tubular reactors, hydrolysis, and decarboxylation are achieved in standard reactors. Optimal bromination conditions were identified as 2.2 equivalent bromination reagent, temperature>60℃, and atmospheric pressure. The fluorination conditions mirror those of bromination, with the fluorinating agent being 2.2 equivalent and a reaction temperature of 150℃. For hydrolysis and decarboxylation, 50% sulfuric acid concentration at 90℃ was optimal, yielding a crude product with a 99.60% G.C. content and a 91.25% efficiency. The outlined production process of 1,1-difluoro acetone boasts remarkable cost efficiency and procedural simplicity, positioning it favorably for industrial applications. This innovative approach promises significant manufacturing cost reductions, endowing fungicides with a fluoropyrazole ring a competitive edge in the market. Such advancements are anticipated to foster market expansion, ultimately benefiting agricultural practitioners.

 © 2023 The Authors. Published by IASE.

 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

 Keywords

 Bromination, Fluorination, β-Ketoacid esters, 1,1-difluoro acetone, Succinate dehydrogenase inhibitor

 Article history

 Received 24 June 2023, Received in revised form 19 October 2023, Accepted 7 November 2023

 Acknowledgment 

We thank Mr. Mingchun Wang, chairman of Suqian Keylab Biochemical Co., Ltd., for his financial support.

 Compliance with ethical standards

 Conflict of interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

 Citation:

 Lin W, Chai P, Cao L, Kang L, and Jiang X (2023). An elementary study of the industrialized preparation of 1,1-difluoro acetone: Starting material of fluoropyrazole succinate dehydrogenase inhibitor. International Journal of Advanced and Applied Sciences, 10(11): 190-201

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 Figures

 Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 

 Tables

 No Table

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