3026
J. Org. Chem.
1981,46, 3026-3029
column chromatography[silica gel; hexane-chloroform (31) and 3 4 (Phenylse1eno)methyll-6-( phenylseleno)-2-oxabicyclo[2.2.2]wtane (8a) and 4-(Phenylseleno)-7-[(phenylseleno)chloroform as eluents], IH NMR measurement revealed that the product contained more than 90% of l b and less than 10% of methyl]-6-oxabicyclo[3.2.l]octane (ab). The reaction and la by integration of signals due to methine protons. workup procedures were analogous to those described above (4Acid-Catalyzed Isomerization of 4b to 4a. To a solution vinylcyclohexene, 0.109 g, 1mmol; reflux 8 h). Liquid chromatographic analysis [hexane-chloroform (91) as eluent, benzoof 4b (0.141 g, 0.5 mmol) in methanol (2 mL) was added hydrogen phenone as internal standard] showed the presence of 8a (0.415 chloride (36.5% aqueous HC1,0.05 mL; 0.5 mmol as HCl), and the resulting solution was stirred under reflux for 5 h. After the mmol, 42%) and 8b (0.018 mmol, 2%). A mixture of Sa and 8b workup procedure as described above, the yellow oil obtained was was isolated in a same way as described above: yellow oil; IR (film) 3060,2950,1589,1475,1435,1210,1070,1025,980,890,740,690 purified by column chromatography [silica gel; hexane-ethyl acetate (201) as eluent] to give 4 (0.111 g, 0.39 mmol, 79%). The cm-’; ‘H NMR 6 1.3-2.4 (m, 7 H), 2.6-3.3 (m, 2 H), 3.3-3.9 (m, 1H), 3.4-4.6 (m, 2 H), 7.1-7.7 (m, 10 H); ’% N M R 6 25.5 (t),26.8 4a/4b isomer ratio was estimated to be 80:20 by integration of the signals due to the methine protons in ‘H N M R spedrum. The (t),31.9 (t), 32.5 (t), 38.7 (t), 44.7 (d), 68.9 (d),%79.0 (d), 81.0 (d), same reaction of 4b in methanol containing phenyl selenocyanate phenyl signals. Anal. Calcd for CJ-InOSez: C, 55.06; H, 5.08. (2 molar equiv) and copper(I1) chloride (1 molar equiv) as well Found C, 55.27; H, 5.11. as hydrogen chloride gave the same result, indicating that hyAcid-Catalyzed Isomerization of l b to la. To a solution drogen chloride worked as a catalyst in this isomerization reaction. of l b (0.436g, 1mol)and phenyl selenrxyanate (0.364g, 2 mmol) in methanol (20mL) containinghydrcgen doride (36.5% aqueous Registry No. la, 75494-81-4;lb, 70187-90-5;2a, 72695-46-6;2b, HCl, 0.1 mL, 1mmol as HCl) was added copper(II) chloride (0.314 72695-47-7; 3a, 32160-45-5; 3b, 4277-34-3; 4a, 77552-07-9; 4b, g, 1 mmol), and the resulting mixture was stirred under reflux 77552-08-0;cis-5a, 72991-21-0;trans-5a, 72991-22-1;5b, 72991-23-2; for 5 h. Water (50 mL) was added, and the products were excis-6, 72991-24-3; trans-6, 72991-25-4; cis-7, 72991-26-5; trans-7, tracted with chloroform (3 X 20 mL). The organic layer was 72991-27-6;8a, 72991-287;8b, 72991-29-8;(2,2)-1,5-~yclooctadiene, washed with brine, dried over MgSO,, and evaporated in vacuo 1552-12-1; phenyl selenocyanate, 2179-79-5; copper(I1) chloride, to leave a yellow oil. After removal of phenyl selenocyanate by 7447-39-4;9-oxabicyclo[3.3.l]nonane,281-05-0;9-oxabicyclo[4.2.1]nonane, 284-20-8; 1,5-hexadiene, 592-42-7; diallyl ether, 557-40-4; diallyl sulfide, 592-88-1;4-vinylcyclohexene, 100-40-3. (24) Attributed to minor component.
Rearrangements of Penicillin Sulfoxides. 2.’ Spectral Data and X-ray Crystallography of the Novel Imidazo[li,l-c][ 1,4]thiazine Ring System Abraham Nudelman* Chemistry Department, Bar-Ilan University, Ramat-Can, Israel
Tali E. Haran and Zippora Shakked* Department of Structural Chemistry, The Weizmann Institute of Science, Rehouot, Israel
Received December 30, 1980
The novel imidazo[5,1-c][1,4]thiazinering system has been obtained by rearrangement of penicillin sulfoxide esters upon treatment with ethoxycarbonylisocyanate. The unexpected structure of the rearrangement product 4b was established by X-ray analysis. A mechanism involving C6-S cleavage and the formation of an episulfonium ion, D, is postulated. Penicillin sulfoxides undergo numerous rearrangements to a variety of ring systems.2 A number of publications3 have described the attempted synthesis of the elusive penicillin sulfilimines. In the course of our investigation we treated penicillin sulfoxide esters l4 with ethoxycarbonyl isocyanates with the aim of preparing the corresponding sulfilimines.6 This paper describes the physical, (1) A. Nudelman and R. J. McCaully, J. Org. Chem., 42,2887 (1977). (2) For recent reviews see: (a) E. H. Flynn, Ed.,“Cephalosporinsand Penicillins, Chemistry and Biology”, Academic Press, New York, 1972; (b) D. H. R. Barton, Pure Appl. Chem., 33,1(1973); (c) R. D. G. Cooper, L. D. Hatfield, and D. 0. Spry, Acc. Chem. Res., 6, 32 (1973); (d) A. Nudelman, Int. J.Sulfur Chem., Part B, 7 , l (1972); (e) A. Nudelman, Phosphorus Sulfur, 2, 51 (1976); (0 A. Nudelman, ibid., 9, 1 (1980). (3) (a) M. Numata, Y. Imashiro, I. Minamida, and M. Yamaoka, Tetrahedron Lett., 5097 (1972); (b) J. E. G. Kemp, D. Ellis, and M. D. Cloiser, ibid., 3781 (1979). (4) D. H. R. Barton, F. Comer, D. G. T. Greig, P. G. Sammes, C. M. Cooper, G. Hewitt, and W. G. E. Underwood, J. Chem. SOC.C, 3540 (1971). (5) R. W. Lamon, J. Heterocycl. Chem. 6 , 261 (1969).
0022-3263/81/1946-3026$01.25/0
spectroscopic, and X-ray data, which establish the structure of the novel products produced in the course of the investigation. The reaction took place (Scheme I) when a tetrahydrofuran solution of a penicillin sulfoxide ester, 1: wm heated with 2 mol of ethoxycarbonyl isocyanate 2s for 17 h. A major product was isolated in yields of 54% (la -. 3a), 31% ( l b 3b) and 40% (IC -. 3c).’ Elemental analysis of the products 3a-c indicated that the elements of carbon and nitrogen had been incorporated and that one hydrogen had been lost from the empirical formula of the respective starting materials. High-reso-
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(6) (a) C. King, J. Org. C h e y , 25, 352 (1960); (b) R. Neidlein and E. Heukelbach,Arch. P h r m . (Wedterm,Ger.),199,64(1966); (c) R Appel and H. Rittersbacher, Chem. Ber., 97,852 (1964). (7) R. L. Lewis and D. Walker, British Patent Appl., 2017705; Chem. Abstr., 93,95265 (1980). These authors claim that the expected penand cephams are obtained upon treatment of la with acyl and sulfonyl isocyanates.
0 1981 American Chemical Society
J. Org. Chem., Vol. 46, No. 15, 1981 3027
Rearrangements of Penicillin Sulfoxides
"B Figure 1. Penicillin rearrangement product 4b. Scheme I1
Scheme I 0
II
I\
P
EtO!N=C=O
Et-0-8-N-C-0
EtOCN CO
-
2
1
H
0 n2C02RI
la,'R = C,H,OCH,C=O; R' = CH2C6H,-p-N0, b, R = C,H,CH,C=O; R' = CH,C,H,-p-NO, C, R = C,H,OCH,C=O; R' = CH,C,H,-p-CH,
1 -
-
,S+
R"H
