Uses
2,3-dihydrobenzofuran is widely used in the synthesis of tricyclic compounds and is also an intermediate raw material for the synthesis of some important drugs. It is used in the synthesis of antitumor agents benzofuran sulfonylureas, HIV protease inhibitor amino acid hydroxyethylenesulfonyl, matrix metalloproteinase inhibitor aryl sulfinyl isoxime hydroxamic acid, etc.
Definition
ChEBI: 2,3-dihydrobenzofuran is a member of the class of 1-benzofurans that is the 2,3-dihydroderivative of benzofuran. It has a role as a metabolite.
General Description
Biotransformation of 2,3-dihydrobenzofuran using intact cells of
Pseudomonas putida UV4 has been investigated. 2,3-Dihydrobenzofuran is the intermediate formed during catalytic hydrodeoxygenation of benzofuran.
Synthesis
Step 1: Synthesis of 2-phenoxyethanol
Add 200 ml of anhydrous ethanol to a 10000 m L three-necked round-bottomed flask, dissolve sodium metal (23 g) in it, then add phenol (94 g, 900 mL), 2-chloroethanol (700 mL) , respectively, and heat and reflux until the reaction mixture is neutral. The reaction was tracked by running a plate during the reaction (unfolding agent: chloroform:methanol:benzene=200:1:1 ; Rf=0.3). Ethanol was removed by distillation under reduced pressure with a rotary evaporator, and 500 mL of distilled water was added. It was then extracted with ether three times (about 400 mL each time) and washed several times with dilute sodium hydroxide solution and distilled water respectively (to remove phenol). The ether was then removed by distillation at atmospheric pressure, and the residue was distilled under reduced pressure to collect a fraction of 163-166°C (18 mmHg) was obtained. The ether is a colorless thick liquid, bp : 240-246°C, refractive index: 1.532, d:1.1002, insoluble in water but soluble in ether and alcohol (yield: 75 %).
Step 2: Synthesis of 2,3-dihydrobenzofuran
To a 250 mL three-necked round-bottomed flask, 2-phenoxyethanol (50 g) and zinc chloride (5 g) were added and heated to 225°C reflux with mixing and stirring, then slowly reduced to 190C reflux. The reaction was carried out over 5h with a running plate to follow the reaction (unfolding agent:chloroform:methanol:benzene=20:1:1 ; Rf=0.6). Cooling, distillation under reduced pressure and collection of (88-90)°C ( 18 mmHg) fraction gave the title compound. The compound was a colorless liquid, b p : 188-189C, refractive index: 1.549, d 1.053 , yield: (70%).
