New Manufacturing Route to Picoxystrobin - Organic Process

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A New Manufacturing Route to Picoxystrobin Yu Chen, Huan Lu, Hui Dai, Wansheng Yu, and Xianhua Pan Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.5b00371 • Publication Date (Web): 26 Jan 2016 Downloaded from http://pubs.acs.org on January 27, 2016

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Organic Process Research & Development

A New Manufacturing Route to Picoxystrobin Yu Chen,1),2) Huan Lu,2 )Hui Dai,2) Wansheng Yu,2) Xianhua Pan1),2)*

1) School of Perfume and Aroma Technology, Shanghai Institute of Technology, 100 Haiquan Rd., Shanghai, 201418, P.R. China. 2) Shanghai Research Institute of Fragrance and Flavor Industry, 480 Nanning Rd., Shanghai, 200232, P.R. China.

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ABSTRACT: A new and efficient manufacturing technology is disclosed in present work for the preparation of picoxystrobin, in which all the intermediates can be used directly for the next step without purification. Key Words: picoxystrobin, strobilurin fungicides, new route, synthesis.


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INTRODUCTION Picoxystrobin (1, Figure 1) belongs to the group of strobilurin compounds, which delivers a breadth of spectrum and level of activity on cereals that is superior to other current commercial strobilurin fungicides.1 It has moderate uptake into host leaves through the xylem and exhibits translaminar movement. Picoxystrobin (1) was first developed by Syngenta but is now commercialized by Dupont with the trade name Aproach.2 Several synthetic methods of picoxystrobin (1) have been disclosed by Zeneca (the predecessor of Syngenta).3–6 However, these methods suffer from several drawbacks such as use of toxic or highly volatile reagent: Me2SO4, CCl4 and HCO2Me (Bp: 32 oC), separation by chromatography for several steps as well as low total yield., Herein we describe a new manufacturing route to picoxystrobin (1) to expand its application.

Figure 1. Picoxystrobin (1).

RESULTS AND DISCUSSION A novel process is shown in Scheme 1, making it possible to avoid drawbacks of the previous methods. This process started from 2, and none of the intermediates were needed for separation.


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Scheme 1. The whole process to the synthesis of 1

The original plan was to transform compound 2 to compound 16 directly. In order to shorten the reaction steps and avoid the highly volatile or toxic reagent (HCO2Me, Me2SO4), we firstly chose widely used CH(OMe)3 as the reagent. However, to our surprising, CH(OMe)3/Ac2O, which were efficient reagents for 2(3H)-benzofuranone (Figure 2) in the synthesis of azoxystrobin,7 proved very poor for 2. As can be seen from Table 1 and Scheme 2, 16 was hardly produced in the presence of anhydrides such as acetic anhydride or isobutyric anhydride, two effective anhydrides for azoxystrobin7 (Table 1, entries 1–5).

Figure 2. 2(3H)-benzofuranone.

Scheme 2. The reaction of 2 with CH(OMe)3 in the presence of anhydrides


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Table 1. The reaction of 2 with CH(OMe)3 in the presence of anhydridesa Entry

CH(OMe)3

Anhydrides

Yieldb

1

2.0 equiv

acetic anhydride (8.0 equiv)

New Manufacturing Route to Picoxystrobin - Organic Process

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