Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for constructing dihydrobenzofuran skeleton compound by oxidative coupling of two C-H bonds

A technique of skeleton compound and oxidative coupling reaction, applied in chemical instruments and methods, compounds of group 4/14 elements of the periodic table, organic chemistry, etc., can solve unresolved problems

Active Publication Date: 2018-03-13
PEKING UNIV
View PDF0 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The method of oxidative coupling of two aromatic hydrocarbons through two carbon-hydrogen bonds to construct a biaryl ring skeleton has been realized (D.R.Stuart, K.Fagnou Science 2007, 316, 1172), but for relatively inert aryl carbon-hydrogen bonds and The method of oxidative coupling of alkyl carbon-hydrogen bonds to construct carbon-carbon bonds has not yet been solved

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
  • Method for constructing dihydrobenzofuran skeleton compound by oxidative coupling of two C-H bonds
  • Method for constructing dihydrobenzofuran skeleton compound by oxidative coupling of two C-H bonds
  • Method for constructing dihydrobenzofuran skeleton compound by oxidative coupling of two C-H bonds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0087] Embodiment 1, the preparation of compound 1 (method A)

[0088] (1) Preparation of the compound shown in the substrate formula A-1

[0089] The compound shown in formula A-1 is prepared according to the following reaction equation, and the specific steps are as follows:

[0090]

[0091] Step 1: In a 100 mL round bottom flask, add 5-hydroxy-2-methylbenzoic acid (7.6 g, 50.0 mmol), concentrated HCl (5.0 mL) and MeOH (30.0 mL). The reaction system was refluxed for 12h. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. Then use ethyl acetate:petroleum ether=1:8 to directly separate the target product 5-hydroxy-2-methylbenzoic acid methyl ester (8.25g, 99% isolated yield).

[0092] The second step: in a 100mL round bottom flask, add 5-hydroxy-2-methylbenzoic acid methyl ester (3.32g, 20.0mmol), Boc 2 O (21.0 mL, 4.6 equiv), Mg (ClO 4 ) 2 (893.0 mg, 0.2 equiv) and DCM (50.0 mL). The reaction system was refluxed f...

Embodiment 2

[0105] Embodiment 2, the preparation of compound 2 (method A)

[0106] (1) Preparation of the compound shown in the substrate formula A-2 (SN-type reaction)

[0107] The compound shown in formula A-2 is prepared according to the following reaction equation, and the specific steps are as follows:

[0108]

[0109] The first step: In a 100mL round bottom flask, add methyl 5-hydroxy-2-methylbenzoate (1.66g, 10.0mmol), 2-bromopropane (1.23g, 1.0equiv), K 2 CO 3 (5.53g, 4.0equiv), n Bu 4 NBr (65.0 mg, 2 mol%), and MeCN (20.0 mL). The reaction system was refluxed for 12h. After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure. Then use ethyl acetate:petroleum ether=1:10 (EtOAc:PE=1:10) to get the target product 5-isopropoxy-2-methylbenzoic acid methyl ester (1.85g, 89% isolated product Rate).

[0110] The second step: In a 100mL round bottom flask, methyl 5-isopropoxy-2-methylbenzoate (0.416g, 2.0mmol), LiOH . h 2 O (0.49g...

Embodiment 3

[0122] Embodiment 3, the preparation of compound 3 (method A)

[0123] (1) Preparation of the compound shown in the substrate formula A-7 (SN-type reaction)

[0124] The reaction equation is as follows, and the preparation method is the same as in Example 2.

[0125]

[0126] The structural confirmation data is as follows:

[0127] 1 H NMR (400MHz, CDCl 3 )δ7.59(d, J=1.9Hz, 1H), 7.16(d, J=8.4Hz, 1H), 7.00(dd, J=8.3, 2.1Hz, 1H), 4.36(dt, J=12.0, 6.0 Hz,1H),2.57(s,3H),1.82–1.67(m,1H),1.65–1.52(m,1H),1.49–1.20(m,10H),0.88(t,J=6.3Hz,3H) . 13 C NMR (100MHz, CDCl 3 )δ172.65, 156.11, 133.18, 132.96, 128.83, 121.45, 118.02, 74.34, 36.43, 31.82, 29.58, 29.27, 25.53, 22.67, 21.22, 19.67, 14.12. HRMS (ESI) Calcd for C 17 h 27 o 3 [M+H] + :279.1951; found: 279.1955.

[0128] (2) Preparation of Compound 3

[0129] Compound 3 is prepared according to the following reaction equation, and the specific steps are as follows:

[0130]

[0131] 0.3mmol of the compound shown in ...

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 method for constructing a dihydrobenzofuran skeleton compound by oxidative coupling of two C-H bonds. According to the method, an intramolecular oxidative coupling reaction of carbon-hydrogen bonds is carried out on a carbon hydrogen bond C(sp<2>)-H at the ortho-position of carboxyl on an aromatic ring in an alkoxy substituted benzoic acid derivative and a carbon-hydrogenbond C(sp<3>) on an alkoxy group for constructing a carbon-carbon bond, and then the dihydrobenzofuran skeleton compound is obtained. The method provided by the invention has an important applicationvalue.

Description

technical field [0001] The invention relates to a method for constructing a dihydrobenzofuran skeleton compound through oxidative coupling of two C-H bonds. Background technique [0002] Building carbon-carbon bonds is an important part of organic synthesis. The traditional method of constructing carbon-carbon bonds is through the coupling reaction of organic halides and organometallic reagents (N. Miyaura, K. Yamada, A. Suzuki, Tetrahedron Lett. 1979, 36, 3437-3440). Recently, great progress has been made in the construction of carbon-carbon bonds from the activation of carbon and hydrogen (R.G.Bergman, Nature 2007, 446, 391-393; O.Daugulis, H.-Q.D., D.Shabashov.Acc.Chem.Res.2009, 42, 1074-1086), for example, one of the organohalide or organometallic reagent in the reactant is replaced by an alkane or an arene. Generally, the carbon-hydrogen bond activation method is to use the strategy of directing group, substrate itself and special site (X.Chen, C.E.Goodhue, J.-Q.Yu, J...

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
IPC IPC(8): C07D307/79C07D307/91C07F7/18
CPCC07D307/79C07D307/91C07F7/1804C07F7/1892
Inventor 施章杰施江陵王丁张西沙
Owner PEKING UNIV