No abstract

No abstract

The facile cleavage of the heterocyclic ring of trans-2-amino-3a,4,5,6,7,7a-hexahydrobenzoxazole (111) is described. Hydrolysis of the amincmxazoline I11 gave trans-Zhydroxycyclohexylurea (V). Methanolysis of I11 afforded a mixture of pseudoureas, IVa and IVb, from which a pure tautomer was isolated. In boiling benzene containing a catalytic amount of ptoluenemlfonic acid, I11 waa converted to the trimeric biguanide VI. The characterization and proof of the skeletal structure of VI is described. The corresponding cis-aminohexahydrobenzoxazole I was found to be stable under identical conditions. Cis and trans-2-amino-3aI4,5,6,7,7a-hexahydrobenaoxazole (I and 111) were prepared as part of a study directed toward the synthesis of cyclic carbamates and pseudoureas of potential pharmacological interest. The known cis-isomer I was prepared from cyclohexene by the method of Birckenbach and Linhard.1 Ia 0 I Although the original investigators' did not assign the stereochemistry to I, the method of preparation assures a cis-fusion.2 This conclusion was confirmed by the unambiguous synthesis of the corresponding trans-isomer 111.The Vans-isomer 111 was prepared in good yield by the cyclization of trans-2-aminocyclohexanol (1I)a with cyanogen bromide4s6 under well defined conditions. From one experiment before these conditions were determined, a 15% yield of I11 was obtained in addition to an 8. 5% yield of a basic crystalline trimer of 111, m.p. 176-176.5'.(1) L. Birckenbach and M. Linhard, Ber., 64, 1081 (1931). (2) Cf. the reaction of cyclohexene with iodine in the presence of silver ptoluenesulfonate to give trans-Ziodocyclohexyl ptoluenesulfonate, S. Winstein, E. Grunwald, and L. L. Ingraham, J. Am. C h . Soc., 70,821 (1948) and the reaction of trans-Zbenzamidocyclohexanol with thionyl chloride to give &2-phenyl-3a,4,5,6,7,7a-hexahydrobensoxazole, W. S. Johnson and E. N. Schubert, J. Am. Chem. Soc., 72,2187 (1950). (3) Prepared by the ammonolysis of cyclohexene oxide by the excellent method of L. R. Hawkina and R. A. B. Bannard, Can. J. Chem., 36,220 (1958). (4) Cf. the reaction of o-aminophenol with cyanogen bromide to give Zaminobensoxazole, M. P. Pierron, Ann. chim. et. p h k~. , 181 15, 191 (1908). i.3) I r :b interesting to note that a related reaction, cyclization of trans-2aminocyclohenol with phosgene is reported to give only low yields of the oxazolidinone, M. Mousseran, F. Winternitz, and M. Mousseron-Canet, Bull. 9oc. chirir. Frame, 737 (1953).This substance (hereafter referred to as the trimer VI) exhibited an ultraviolet absorption maximum at 234 mp (e 17,500), infrared absorption bands at 3.00,3.23,5.97,6.12, and 6.40 p and was tentatively assigned the s-triazine structure VI1 on the basis of the spectral and analytical data. However, an authentic sample of VII, prepared by the reaction of the aminoalcohol I1 with cyanuric chloride in the presence of sodium hydroxide,s was found to be different from VI by melting point and infrared spectroscopy.Several observations concerning the chemical behavior of I11...

The synthesis of four potential starting materials for the preparation of 2-amino-1-(2-imidazoliti-2-yl^-imidazolines is described. Treatment of 2-(methylthio)-2-imidazoline (6) with 2-(methylthio)-2-imidazoline hydriodide (7) gave 1-(2-imidazolin-2-yl )-2-(methylthio )-2-imidazoline hydriodide (9) and 1-(2-imidazolin-2-yl )-2-(methylthio)-2-imidazoline hydriodide methanethiol (8). Two minor products, l-( 2-imidazolin-2-yl)-2-[2-(methylthio)-2-imidazolin-l-yl]-2-imidazoiine hydriodide (10) and 2,3,8,9-tetrahydro-5-(methylthio)-7# -imidazo[2,3-fe] [l,3,5]triazepine hydriodide (11), were also obtained. Reaction of 2-(methylthio)-2-imidazoline hydriodide (7) with triethylamine afforded triethyl [l-(2-imidazolin-2-yl)-2-imidazolin-2-yl] ammonium iodide hydriodide methanethiol ( 12) and 1-(2-imidazolin-2-yl)-2-(methylthio)-2-imidazoline dihydriodide methanethiol (13). The determination of the structures of the aforementioned compounds and their relationship to Jaffé's base, 1-(2-imidazolin-2-yl )-2-imidazolidinethione (5), is described. A novel hydrolysis, the transformation of 1-(2-imidazolin-2-yi)-2-(methylthio)-2-imidazoline dihydriodide methanethiol (13) to 8,8-dimethyl dithiocarbonate ( 17) and 2-[(2-aminoethyl)amino]-2-imidazoline dihydroiodide (18), was observed. Evidence which suggests that previously described conversion of 6 to 1-(2-imidazolin-2-yl)-2-imidazolidinone ( 14)1 234 proceeds via alkoxylimidazolinylimidazoline 21 is presented.Structures l1 and 22 initially assigned to Jaffé's base, the product of the interaction of ethylenediamine (3) and thiophosgene (4),1 were subsequently shown to be incorrect; the correct structure 5 was established(1) M. Jaffé and B.

111Several years ago we described the preparation of 1veratrylcarbonyl-l-azaspiro[4.5]decane (2) by the acidcatalyzed s piroa mi d a t i o n of N-[ 3-( 1-c y cl o h ex en-1-yl)propyl ] -2-(3,4-dimethoxyphenyl)acetamide (1) (2). We have utilized this process for the synthesis of the hitherto unreported 1,8-diazaspiro[4.5]decane system, which is the subject of this Note. Treatment of 4(2-~arbamoylethyl)pyridine (3) (3) withbenzyl chloride gave quaternary salt 4 which was reduced with sodium borohydride to tetrahydropyridine 5 (4). Reduction of 5 with lithium aluminum hydride afforded amine 7 which was converted to amides 8a, 8b and 8c.Unlike neutral amide 1, which was cyclized readily to 2 by polyphosphoric acid a t 25", basic amides 8a, 8b and 8c were stable in this medium to 150"; at higher temperatures 8a, 8b and 8c were converted slowly to complex mixtures according to thin-layer chromatography. Like 1, neutral amides 9a and 9b, prepared by treatment of 8a and 8b with ethyl and methyl chloroformate (5), respectively, were cyclized smoothly to spiro[4.5]decanes 10a and lob.The spectral properties (see Experimental) of spiro-[4.5]decanes 10a and 10b were consistent with the structures assigned to these compounds by analogy with the transformation of I to 2.Cyclization of amide 5 with polyphosphoric acid at 145" afforded l-oxa-8-azaspiro[4.5] decane (6) (6), the infrared spectrum of which exhibited an intense absorption band at 1770 cm-' , characteristic of a y-lactone (7). C"2 I 3 CI-5