New Manufacturing Route to Picoxystrobin - Organic Process

Publication Date (Web): January 26, 2016. Copyright © 2016 ... Development of an Efficient, Safe, and Environmentally Friendly Process for the Manufa...
9 downloads 7 Views 918KB Size
Subscriber access provided by University of Florida | Smathers Libraries

Full Paper

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

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Organic Process Research & Development is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 16

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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.

ACS Paragon Plus Environment

1

Organic Process Research & Development

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 16

TOC graphic

ACS Paragon Plus Environment

2

Page 3 of 16

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Organic Process Research & Development

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.

ACS Paragon Plus Environment

3

Organic Process Research & Development

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 16

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.

ACS Paragon Plus Environment

4

Page 5 of 16

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Organic Process Research & Development

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

ACS Paragon Plus Environment

5

Organic Process Research & Development

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 16

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)