Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Solvent-promoted method for selective dehydrogenation of tetrahydroisoquinolines

A technology of tetrahydroisoquinoline and compounds, applied in the field of racemization, to achieve the effects of simple reaction operation, high chemoselectivity, and mild reaction conditions

Active Publication Date: 2019-03-19
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few reports of partial dehydrogenation of cyclic imines

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
  • Solvent-promoted method for selective dehydrogenation of tetrahydroisoquinolines
  • Solvent-promoted method for selective dehydrogenation of tetrahydroisoquinolines
  • Solvent-promoted method for selective dehydrogenation of tetrahydroisoquinolines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Embodiment 1: optimization of conditions

[0033] In air, put substrate 1a (0.2 mmol) into a 25 mL Schlenk bottle, and add 1.0 mL of solvent, then stir at 100°C for 24 hours, then cool to room temperature, remove the solvent under reduced pressure, and determine the conversion rate by crude nuclear magnetic spectrum , and then separated by column. (Eluent: the volume ratio of petroleum ether and ethyl acetate is 5:1), and the target product 1-phenyl-3,4-dihydroisoquinoline was obtained. Its reaction formula is as follows:

[0034]

[0035] The conversion rate and the ratio of the two products are determined by the reaction crude product 1 H NMR to determine, see Table 1 for details.

[0036] Table 1. Optimization of reaction conditions for selective dehydrogenation of substituted tetrahydroisoquinolines a

[0037]

[0038]

Embodiment 2

[0039] Example 2: Substrate Expansion

[0040]

[0041] Productivity is the separation yield, separated by column (eluent: the volume ratio of petroleum ether and ethyl acetate is 5:1), the ratio of partial dehydrogenation product and complete dehydrogenation product is determined by nuclear magnetic rough spectrum, see Table 2 .

[0042] Table 2. Tetrahydroisoquinoline Selective Dehydrogenation Synthesis 2 a

[0043]

[0044] Embodiment 2: Gram scale test

[0045]

[0046] In air, the substrate 1-phenyl-1,2,3,4-tetrahydroisoquinoline (1.0 g, 4.78 mmol) was charged into a 25 mL Schlenk bottle, and 5.0 mL DMF was added, then stirred at 100°C After 3 days, it was cooled to room temperature, and the solvent was removed under reduced pressure. The conversion rate > 95% and the product ratio > 20:1 were determined by crude NMR spectroscopy. 0.827 g was isolated with a yield of 83.5%.

Embodiment 3

[0047] Embodiment 3: chiral tetrahydroisoquinoline racemization test

[0048]

[0049] Add single enantiomer 1-phenyl-1,2,3,4-tetrahydroisoquinoline substrate (84mg, 0.4mmol, 96.9%ee) into the reaction flask, add DMF to dissolve, heat up to 100°C and stir Reaction for 24 hours, thin-layer chromatographic analysis to detect the reaction process, until the raw materials completely disappeared, then remove the solvent under reduced pressure, without any other treatment, to obtain 1-phenyl-3,4-dihydroisoquinoline, and then to the system Add 3mL of methanol, then add (30mg, 0.8mmol) sodium borohydride in batches, stir the reaction at room temperature, and detect the reaction process by thin-layer chromatography, until the raw material completely disappears, add a small amount of water to quench the reaction, and react with ethyl acetate The aqueous phase was extracted 3 times, the organic phase was combined, washed once with saturated brine, dried over anhydrous sodium sulfate, ...

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

A solvent-promoted method for synthesizing 1-substituted-3,4-dihydroisoquinolines through selective partial dehydrogenation of 1-substituted-1,2,3,4-tetrahydroisoquinoline compounds. For simple and easy-to-obtain cyclic amine compounds such as tetrahydroisoquinoline compounds, the corresponding imine compounds can be obtained by selective dehydrogenation, the conversion rate is high, and the ratio of partial dehydrogenation products to complete dehydrogenation products is greater than 20: 1. The invention is simple and practical to operate, has mild reaction conditions, and greatly reduces the actual cost. In addition, the method for synthesizing 3,4‑dihydroisoquinoline by direct dehydrogenation of tetrahydroisoquinoline has the advantages of atom economy and environmental friendliness.

Description

technical field [0001] The present invention relates to a kind of selective partial dehydrogenation of 1-substituted-1,2,3,4-tetrahydroisoquinoline promoted by solvent to synthesize 1-substituted-3,4-tetrahydroisoquinoline compound and chiral A method for the racemization of tetrahydroisoquinolines. Background technique [0002] Imines are a very useful class of substrates in synthetic organic chemistry, such as cyclization reactions and addition reactions of nucleophiles. The synthesis of imines by direct oxidative dehydrogenation of amines is also a very important synthetic method. However, it is often necessary to add equivalent oxidants or hydrogen acceptors (references one: (a) Orito K., Hatakeyama T., Takeo M., Uchiito S., Tokuda M., Suginome H.Tetrahedron 1998,54,8403;( b) Ajzert K.I., Takács K. Liebigs Ann. Chem. 1987, 1061; (c) Khatri P.K., Jain S.L., Sivakumar K.L.N., Sain B.Org. Biomol. Chem. 2011, 9, 3370; (d) Yao W., Zhang Y., Jia X., HuangZ.Angew.Chem.Int.Ed...

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 Patents(China)
IPC IPC(8): C07D217/02C07D217/14C07D217/16
CPCC07D217/02C07D217/14C07D217/16
Inventor 周永贵时磊冯广收姬悦
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com