PREPARATION OF 3=AZABICYCLO[3.2.2]= NONANE AND DERIVATIVES V.
L. BROWN, JR., AND T. E. STANlN
Research Laboratories, Tennessee Eastman Co., Division of Eastman Kodak Co., Kingsport, T znn.
A new nitrogen-containing heterocycle which shows promise as a chemical and pharmaceutical intermediate, 3-arabicyclo [3.2.2Inonone, has been synthesized by the vapor-phase deamination of 1,4-~yclohexanebis(methylamine). Several catalysts have been evaluated for this reaction. A number of derivatives of the new compound have been prepared and some of their physical properties have been measured. The procedure for the preparation of this heterocycle can easily b e expanded to commercial scale.
heterobicyclic ring system has been synthesized. This 3-azabicyclo [3.2.2]nonane (compound 1) is a member of the general group of tropane alkaloids ( 5 ) . NEW
A system,
Table 1.
Catalysts for Deamination of 1,4-Cyclohexanebir(methylamine)
Convn., Catalyst
Tropane-type alkaloid
1
When Malachowski and his coworkers (70) attempted to prepare compound 1, they were able to isolate only 4-methylenecyclohexapemethylamine (compound 2).
H CHzNHz
0 2
By the catalytic deamination of 1,4-~yclohexanebis(methylamine) (compound 3), which was obtained from Eastman Chemical Products, Inc., Kingsport, Tenn., compound 1 is formed in the vapor phase :
c -
Catalyst 350-450' N2
H' ' C H ~ N H ~
1
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3 3"
A number of materials have been tried as catalysts for this reaction (Table I ) . Unless otherwise noted in the table, these data were obtained by using a contact time of 2 seconds (73), a pyrolysis temperature of 390' to 400' C., and a 1 to 1 molar ratio of nitrogen to compound 3. None of the temperatures is corrected. As the data in Table I indicate, this reaction is catalyzed by a broad range of materials; however, these same data indicate that a catalyst is necessary, as shown by the inactivity of materials such as magnesium oxide, cy-alumina, and Vycor chips. Materials which have been found to have fair-to-good catalytic activity include both modified and unmodified 40
Yield, 90b
51.4-95 4
62.1-62,5 63
7G93
60l7l
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18-31 57% 50-63 38-57 25-40
27l68 ... 48-61 66-92 81-96 46-58
a Convn., % = g.-moles of 3consumed/g.-molesof 3fed. Yield, Yo = g.-moles of 1 obtained/g.-moles of 3 consumed. Alcoa Grade F - l , 7-14 mesh. Dauison Silica Gel 30; temperature of reaction zone, 450' C. e Harshaw Mg-XL-7474-18 T , ' / 8 inch, some activity !it 500' C. f Pittsburgh Coke and Chemical Co. -BPL, 4-10 mesh. 0 Alcoa T-61, 100% a-alumina. h Wagner No. 6. No activity between 350' and 550' C. j Dauison TS-55-5406. Girdler K-106, contains SiOz, AllOa, FelOg, CaO, and M g O . Floridin Co., synthetic magnesium silicate. m Dow Type B, dehydrogenation catalyst containing calcium and nickel phosphates and possibly some chromium phosphate.
'
CHa
H CHz"z
Activated aluminac Silica geld Magnesium oxide$ Activated carbonf Tabular aluminag Pumice* Vycor chips' Silica-aluminaj Montmorillonitek Florisil' Dow B m
%a
I&EC P R O D U C T RESEARCH A N D DEVELOPMENT
aluminas (except a-alumina), activated carbons, and natural and synthetic silicates. Metallic catalysts, although active, were usually destructive. 3-Azabicyclo [3.2.2]nonane is a white, crystalline, strongly It absorbs carbon dioxide basic solid (Ka = 3 X readily, and analysis is therefore difficult. It sublimes a t ordinary pressures and temperatures. It readily undergoes the reactions typical of a secondary aliphatic amine. Some of the N-substituted derivatives which have been prepared are listed in Tables 11, 111, IV, and V ; their physical properties are included. Since the structures of some of the derivatives of this new compound are closely related to compounds of known pharmacological activity (2, 3, 77), these new compounds may be of interest in the field of pharmaceutical chemistry. While this paper was being prepared, several papers (7, 6-8, 72) were published concerning some derivatives of compound 1 and their physiological properties. Krieger ( 7 ) and Najer et al. (72) have also prepared compound 11, reported (7, 72, 75) to be an excellent blood pressure-regulating agent. Some of the carboxamides (Table 111) and sulfonamides (Table IV) have structures similar to
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