Synthesis method of o-toluenepicolinamide gamma-C-(sp<3>)H sulfur/selenide compound under catalysis of palladium

A technology of o-tolylamide and tolylamide, which is applied in the field of palladium-catalyzed synthesis of o-tolylamide γ-C-H sulfur/selenoether compounds, can solve the problems of poor atom economy and achieve high selectivity and product yield High and wide substrate applicability

Active Publication Date: 2020-05-08
ZHEJIANG UNIV OF TECH
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] C-H functionalization is an important means to construct thioether compounds, but the research direction of this method mainly focuses on the ortho C(sp 2 )-H activation and C(sp 2 )-S bond construction, C(sp3)-H often has a large reaction inertness in organic research due to its stable bond energy, and requires multi-step reactions to achieve its functionalization and poor atom economy. Direct functionalization reaction has always been the focus and difficulty of research

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis method of o-toluenepicolinamide gamma-C-(sp&lt;3&gt;)H sulfur/selenide compound under catalysis of palladium
  • Synthesis method of o-toluenepicolinamide gamma-C-(sp&lt;3&gt;)H sulfur/selenide compound under catalysis of palladium
  • Synthesis method of o-toluenepicolinamide gamma-C-(sp&lt;3&gt;)H sulfur/selenide compound under catalysis of palladium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030]

[0031] Add N-(o-tolyl) pyridine amide (4.24 grams, 20.0mmol), diphenyl disulfide (2.61 grams, 0.6eq), palladium acetate (449.0 milligrams, 10mol%), potassium acetate ( 3.92 g, 2.0 eq) and tert-butyl hydroperoxide (5.84 g, 2.0 eq), toluene (200.0 mL). Stir at 120 °C for 16.0 h under air atmosphere. Then the mixture was cooled to room temperature, filtered after cooling and concentrated under reduced pressure. Purified by silica gel column chromatography (developing solvent: petroleum ether: ethyl acetate = 40:1) to obtain 4.54 g of the target product as a colorless transparent oil, with a yield of 71%.

[0032] 1 H NMR (400MHz, CDCl 3 )δ10.68(s,1H),8.58(d,J=4.6Hz,1H),8.33(d,J=7.8Hz,1H),8.26(d,J=8.1Hz,1H),7.93(td, J=7.7,1.2Hz,1H),7.53–7.47(m,3H),7.38(t,J=7.4Hz,1H),7.32(t,J=7.1Hz,2H),7.26(d,J=7.2 Hz,1H),7.20 (d,J=7.3Hz,1H),7.09(t,J=7.5Hz,1H),4.24(s,2H). 13 C NMR (101MHz, CDCl 3 )δ162.36, 150.00, 148.13, 137.58, 136.12, 135.14, 131.80, 130.47, 128.90, 128.66, 12...

Embodiment 2

[0034]

[0035] Add N-(o-tolyl) pyridine amide (4.24 grams, 20.0mmol), p-toluene disulfide (2.95 grams, 0.6eq), palladium acetate (359.2 mg, 8mol%), potassium acetate ( 3.92 g, 2.0 eq) and tert-butyl hydroperoxide (5.84 g, 2.0 eq), p-xylene (100.0 mL). Stirred at 120°C for 12.0h under air atmosphere. Then the mixture was cooled to room temperature, filtered after cooling and concentrated under reduced pressure. Purified by silica gel column chromatography (developing solvent: petroleum ether: ethyl acetate = 40:1) to obtain 4.56 g of the target product as a colorless transparent oil, with a yield of 68%.

[0036] 1 H NMR (400MHz, CDCl 3)δ10.68(s,1H),8.65(d,J=4.4Hz,1H),8.35(d,J=7.8Hz,1H),8.27(d,J=8.1Hz,1H),7.95(t, J=7.2Hz, 1H), 7.53(dd, J=7.1, 4.8 Hz, 1H), 7.43(d, J=7.9Hz, 2H), 7.38(d, J=7.6Hz, 1H), 7.19(d, J=7.2Hz,1H), 7.15–7.09(m,3H),4.20(s,2H),2.36(s,3H). 13 C NMR (101MHz, CDCl 3 )δ162.35, 150.08, 148.13, 137.59, 137.54, 136.10, 132.57, 131.27, 130.48, 129.66, 128....

Embodiment 3

[0038]

[0039] Add N-(o-tolyl)pyridine amide (4.24 grams, 20.0mmol), 4,4'-dimethoxydiphenyl disulfide (3.90 grams, 0.7eq), palladium acetate (538.8 mg, 12mol%), potassium acetate (3.92g, 2.0eq) and tert-butyl hydroperoxide (5.84g, 2.0eq), toluene (80.0ml). Stirred at 110°C for 18.0h under air atmosphere. Then the mixture was cooled to room temperature, filtered after cooling and concentrated under reduced pressure. Purified by silica gel column chromatography (developing solvent: petroleum ether: ethyl acetate = 40:1) to obtain 5.4 g of the target product as a colorless transparent oil, with a yield of 77%.

[0040] 1 H NMR (400MHz, CDCl 3 )δ10.65(s,1H),8.69(d,J=4.3Hz,1H),8.36(d,J=7.8Hz,1H),8.27(d,J=8.0Hz,1H),7.99–7.93( m,1H),7.54(dd,J=6.9,5.2Hz,1H),7.46(d,J=8.6Hz,2H),7.41–7.35(m,1H),7.09(t,J=7.1Hz,2H ),6.84(d,J=8.6Hz,2H),4.14(s,2H),3.83(s,3H). 13 C NMR (101MHz, CDCl 3 )δ162.35, 159.72,150.11,148.13,137.56,136.01,135.34,130.53,128.85,128.46,127.29, 126.42,124.59,122...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses a synthesis method of an o-toluenepicolinamide gamma-C-(sp<3>)H sulfur/selenide compound under the catalysis of palladium. The method comprises the following steps: dissolvinga compound represented by formula (I) and a compound represented by formula (III) in an organic solvent, reacting for 8-24 h at the temperature of 100-130 DEG C under the action of a catalyst, an oxidizing agent and an alkaline substance, and carrying out post-treatment on the obtained reaction solution after the reaction is finished in order to obtain the gamma-C(sp<3>)-H sulfur/selenide compoundrepresented by formula (II). The method successfully realizes direct synthesis of the gamma-C(sp<3>)-H sulfide/selenide compound for the first time, avoids the use of benzyl bromide, thiophenol and other high-risk and high-toxicity compounds in a traditional method, and has few side reactions. Meanwhile, sulfone compounds with high application values and corresponding hydrolysates can be synthesized from the product through simple oxidation and hydrolysis. The method is simple and convenient to operate, mild in reaction conditions, high in selectivity, high in product yield and wide in substrate applicability, and is an efficient organic synthesis means.

Description

technical field [0001] The invention relates to a palladium-catalyzed synthesis method of o-tolylamide gamma-C-(sp3)H sulfur / selenoether compounds, belonging to the field of organic synthesis. Background technique [0002] Thioether compounds have a wide range of biological activities, and are the key components of many drugs and active intermediates, such as the dibenzoxazepine atypical antipsychotic quetiapine. At the same time, thioethers are also key intermediates for the construction of sulfone drugs or active substances, and the oxidation of thioethers is one of the common methods for synthesizing sulfone compounds. Therefore, obtaining thioether compounds quickly and efficiently has always been a hot spot of concern. [0003] The traditional method is to use the nucleophilic substitution reaction between thiophenol and benzyl bromide to synthesize thioether compounds, but there are many by-products, difficult preparation of raw materials and high toxicity. In modern...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07D213/81C07D215/48C07D217/26C07D231/56
CPCC07D213/81C07D215/48C07D217/26C07D231/56
Inventor 谢媛媛侯加浩王凯程科
Owner ZHEJIANG UNIV OF TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap