7-Aza-11,12-Dioxa-6-phenyl-tricyclo[7,2,1,0.sup.1.6 ]dodecane derivatives and process for their preparation

#The development of general anesthetics for the relief of pain associated with surgical procedures represents one of the oldest and most successful areas in the field of medicinal chemistry. With the diversity of chemical structures now comprising this class of pharmaceuticals, it is ironical that one of the oldest agents nitrous oxide, a gas, is still widely used as the agent of choice in a number of surgical procedures.

#General anesthetics are agents which reversibly produce a state of unconsciousness and absense of pain sensation. In general, the depth of anesthesia depends upon the dose of the agent used, but the overall pharmacological effects are a property of the specific agent employed as well as of the dose. In addition to their primary action as depressants of the central nervous system, general anesthetics also alter a variety of non-central functions controlled by several target organs which provide distinct pharmacological profiles for each of the various compounds in this class.

#The criteria for an ideal general anesthetic agent can be made according to the needs of the patient, anesthesiologist and the surgeon. As far as the patient is concerned, the agent should provide a pleasant induction, be rapid in onset, allow an uneventful recovery and, above all, it must be safe. From the anesthesiologist's point of view, it should have a wide clinical margin of safety, enable moment to moment control of the depth of anesthesia, permit high oxygen levels and be non-explosive. In order to perform his tasks, the surgeon prefers that the patient feels no pain, lies still to invasive instruments such as the scalpel, has good skeletal muscle relaxation and minimal reflex activity and that the agent does not induce bleeding. As yet, no general anesthetic meets all the criteria of the ideal agent and thus, the search is still continuing.

#A solution of 8.18 g of 2-methylamino-2-phenylcyclohexanone and 6.03 g of epibromohydrin and 4.45 g of triethylamine in 30 ml of toluene was refluxed for 18 hrs. The mixture was cooled and decanted through the insoluble material. The solid was triturated several times with benzene and the benzene extract was combined with the above toluene solution and concentrated in vacuo. The resulting residue was distilled from a Kuegelrohr at 123.degree.-150.degree. C./0.05 mm to yield 6.72 g of a liquid. The material was dissolved in a minimum amount of methylene chloride and placed on a column containing 80 g of a silica gel. The column was eluted with 150 ml methylene chloride and then with 5% ethyl ether/methylene chloride in fractions of 50 ml. Fractions 4 to 8 yielded 5.53 g of a homogeneous solid (thin layer chromatogram). This material was Kuegelrohr distilled to give 5.16 g (49.7%) of 7-aza-11,12-dioxa-7-methyl-6-phenyltricyclo[ 7,2,1,0.sup.1,6 ]dodecane; bp: 115.degree.-125.degree. C./0.4 mm.

#An etherial solution of 5.0 g of this material was treated with gaseous hydrochloric acid which precipitated a gum that solidified on standing in ethyl ether. This material was triturated with 50 ml of boiling acetone, filtered and dried in a drying pistol over refluxing acetone to yield 4.46 g of the hydrochloride salt of the above compound; mp 228.degree.-229.degree. C.

#When in the above Example, the triethylamine was replaced by potassium carbonate, material identical to the above was obtained.