2-aryl-zinc-propionate catalyst and preparation method and use thereof

Patent metadata

Field	Value
Publication number	US-2016326085-A1
Application number	US-201315106194-A
Country	US
Kind code	A1
Filing date	Dec 18, 2013
Priority date	Dec 18, 2013
Publication date	Nov 10, 2016
Grant date	—

Abstract

The present invention belongs to the technical field of chemical catalysts, and particularly relates to a zinc 2-arylpropionate catalyst, a preparation method therefor and use thereof The structural formula of the zinc 2-arylpropionate catalyst of the present invention is one of the following structures. The catalyst can be used for homogeneous catalysis of a 1,2-aryl rearrangement reaction of α-haloarylketal, and especially for synthesis of high yield and environmentally friendly 2-arylpropanonic acid non-steroidal anti-inflammatory analgesic drugs, such as, ibuprofen, ketoprofen, loxoprofen, flurbiprofen, fenoprofen, or naproxen and the like.

First claim

1 . A zinc 2-arylpropionate catalyst of formula (I) or (II)

wherein R 1 and R 2 are respectively selected from hydrogen, a C 1 -C 4 alkyl, a methoxyl, a trifluoromethyl, a halogen, a phenyl, a benzyl; R 1 is ortho-substituted, meta-substituted or para-substituted, mono-substituted or polysubstituted; and R 2 is C-5, C-6, C-7, or C-8 substituted, mono-substituted or polysubstituted.

2 . A method for preparing the zinc 2-arylpropionate catalyst in accordance with claim 1 , comprising the steps of:
(1) an alkaline earth hydroxide is dissolved in a C 1 -C 4 alcohol, 2-arylpropionic acid is added, the reaction being for 0.5-2 h at room temperature to 100° C. to obtain a solution of alkaline earth 2-arylpropionate; said alkaline earth hydroxide is lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, and the molar ratio of the 2-arylpropionic acid to the alkaline earth hydroxide is 1:0.8-1:1.5; (2) a zinc salt or zinc oxide is added into the above-mentioned alkaline earth 2-arylpropionate solution, the reaction being for 0.5-20 h at room temperature to 100° C. to obtain zinc 2-arylpropionate; said zinc salt is zinc chloride, zinc sulphate or zinc acetate; and the molar ratio of said zinc salt or zinc oxide to the alkaline earth 2-arylpropionate is 0.5:1-0.5:1.2.

3 . The method of claim 2 , characterized in that in step (1), the alkaline earth hydroxide is sodium hydroxide, the C 1 -C 4 alcohol is methanol or ethanol, the reaction temperature is 45-55° C., the reaction time is 0.5-2 h, and the molar ratio of the 2-arylpropionic acid to the alkaline earth hydroxide is 1:1-1:1.1.

4 . The method of claim 2 or 3 , characterized in that in step (2), said zinc salt is zinc acetate, and the molar ratio of the zinc acetate to the sodium 2-arylpropionate is 0.5:1-0.5:1.1.

5 . Use of the zinc 2-arylpropionate catalyst of claim 1 in homogeneous catalysis of a 1,2-aryl rearrangement reaction of an α-haloarylketal, characterized in that zinc 2-arylpropionate and an α-haloarylketal are reacted for 1-10 h in a single or mixed aromatic hydrocarbon solvent at 80-160° C. to obtain a 2-arylpropanonic acid non-steroidal anti-inflammatory analgesic drug; said aromatic hydrocarbon solvent is benzene, mono-substituted benzene or multisubstituted benzene; and the molar ratio of the zinc 2-arylpropionate catalyst to the α-haloarylketal is 0.01:1-0.5:1.

6 . The use of claim 5 , characterized in that said aromatic hydrocarbon solvent is toluene, the reaction temperature is 110-120° C., and the molar ratio of the catalyst to the α-haloarylketal is 0.02:1-0.1:1.

7 . The use of claim 5 or 6 , characterized in that said α-haloarylketal has one of the following structures:

wherein Ar is

and X is Cl, Br or I.

8 . The use of claim 5 or 6 , characterized in that said 2-arylpropanonic acid non-steroidal anti-inflammatory analgesic drug is ibuprofen, ketoprofen, loxoprofen, flurbiprofen, fenoprofen, or naproxen.

Assignees

• Univ Fudan

Inventors

• Chen Fener
• He Qiuqin
• Xiong Fangjun
• Chen Wenxue

Classifications

• C07C59/64

  containing six-membered aromatic rings · CPC title

• C07C59/68

  the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring · CPC title

• C07C59/86

  containing six-membered aromatic rings and other rings · CPC title

• C07C57/58

  containing six-membered aromatic rings · CPC title

• C07C57/40

  containing condensed ring systems · CPC title