1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one Chemical Properties

Melting point:

49-50 °C

Boiling point:

119 °C(Press: 0.1 Torr)

Density 

1.300±0.06 g/cm3(Predicted)

storage temp. 

Hygroscopic, Refrigerator, under inert atmosphere

solubility 

Chloroform, Methanol

form 

Solid

color 

White to Off-White

InChI

InChI=1S/C11H10O2/c12-10-11(6-9(11)7-13-10)8-4-2-1-3-5-8/h1-5,9H,6-7H2

InChIKey

WZGFIZUMKYUMRN-UHFFFAOYSA-N

SMILES

C12(C3=CC=CC=C3)C(C1)COC2=O

Safety Information

HS Code 

2918300090

1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one Usage And Synthesis

Uses

Intermediate in the synthesis of Milnacipran (M344600) an antidepressant. A selective norepinephrine and serotonin reuptake inhibitor approved for the management of fibromyalgia.

Reactions

1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one (1POX) is a monomer that belongs to the class of cyclopropane compounds and can be used in the synthesis of polymers. It has been shown to react with benzene, irradiation, monoxide, oxiranyl, acetonitrile and trimeric dyes to form reactive intermediates such as ketones and carboxylic acids. These intermediates can undergo photolysis to produce products such as ketones and carboxylic acids. The wavelength of the light used for photolysis can influence the product formation. 

Synthesis

1. To a solvent mixture of toluene (26.0 kg) and N,N'-dimethyl-2-imidazolidinone (94.9 kg), 60% sodium hydride (27.2 kg, 683 mol) was slowly added, followed by benzeneacetonitrile (40.2 kg, 343 mol). After the dropwise addition was completed at 10 to 20 °C, stirring was continued for 2 h. The mixture was then mixed into the solvent mixture at the same temperature range. 2. A mixture of 1-chloro-2,3-epoxypropane (31.7 kg, 343 mol) and toluene (26.0 kg) was added dropwise over the same temperature range and stirring was continued until the feedstock was completely gone. 3. Upon completion of the reaction, methanol (22.0 kg) and water (120.6 kg) were added for washing followed by phase separation. 4. 24% aqueous potassium hydroxide (159.1 kg) and tetrabutyl ammonium sulfate (1.1 kg) were added to the organic layer and heated under reflux conditions. 5. After removal of the organic phase by phase separation, toluene (69.6 kg) and 35% hydrochloric acid (78.7 kg) were added to the aqueous phase and stirred at 60-70 °C for 2 hours. 6. Phase separation was performed again to separate the organic phase, which was washed twice with 8% aqueous sodium bicarbonate and twice with water in turn. 7. The washed organic layer was concentrated under reduced pressure to give 40.7 kg of 1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one as a pale yellow oil in 68.1% yield. 8. The resulting 1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one oily substance was cooled to induce crystallization.

Structure and conformation

1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one (1POX) is also a substrate for cyclopropane ring formation reactions, which are known for their high reactivity due to the stability of this ring system. The carbonyl group on 1POX is electron withdrawing and stabilizes the planar geometry of 1POX.

References

[1] Patent: WO2005/123709, 2005, A1. Location in patent: Page/Page column 6-7
[2] Patent: EP1767522, 2007, A1. Location in patent: Page/Page column 3
[3] Patent: US2012/165339, 2012, A1. Location in patent: Page/Page column 22-23
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 11, p. 4648 - 4664

1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one(63106-93-4)Related Product Information

• 4'-Hydroxyacetophenone
• Benzyl alcohol
• TPP
• (1S,5R)-1-PHENYL-3-OXA-BICYCLO[3.1.0]HEXAN-2-ONE
• 1-Phenyl-1-cyclopropanecarboxylic acid
• MILNACIPRAN HYDROCHLORIDE