J. CHEM. soc. PERKIN TRANS. 1 1994 Demethoxycarbonylation of Methyl 2,5-and Methyl 3.6-Dialkyl-I H-azepine-I -carboxylates: Formation and Characterization of 2H-, 3H- and 4H-Azepines Kyosuke Satake," Ryoichi Okuda, Michiaki Hashimoto, Yasusi Fujiwara, Hideki Okamoto, Masaru Kimura and Shiro Morosawa Department of Chemistry, Faculty of Science, Okayama University, Tsushima- Naka 3-I -I, Okayama, 700, Japan Demethoxycarbonylation of methyl 2.5-di-tert-butyl-1 H-azepine-1 -carboxylate using 1.8-diazabicyclo5.4.0 undec-7-ene (DBU) gave 3H-azepines. Under similar conditions, methyl 3.6-di- tert-butyl-1 H-azepine-1 -carboxylate gave not only the 3H-azepine but also the isomerized 2H-and 4H-azepines. Application of the reaction to dimethyl and diisopropyl substituted 1 H-azepines showed that bulky alkyl group substitution stabilizes the seven-membered azatriene system.The thermal behaviour of the di-tert-butyl substituted azepines is discussed. Effective deprotection of nitrogen atom-protected 1 H-azepines is of interest in connection with the behaviour of 1H-azepine which can be regarded both as an anti-Huckel 8nelectron system and a ni trogen-containing seven-membered triene system.'A MNDO molecular orbital calculation predicts that 3H-azepine is more stable than 1 H-,2H- (6) or 4H-azepine (8), related to 3H-azepine 7 by the thermally allowed, 1 +hydrogen shift (Table 1). Owing to their instability, the chemical and physical properties of azepines have yet to be experimentally determined.The elegant conversion of methyl 1H-azepine- 1-carboxylate into the 3H-azepine was accomplished by Vogel et al. with iodotrimethylsilane as a demethoxycarbonylating agent, the product being characterized by low-temperature NMR spectroscopy.lb Earlier, we reported the indirect conversion of methyl 2,5- 2a and 3,6-di-tert-butyl-lH-azepine-l-carboxylates 3a into the correspondingly substituted 3H- azepines 4a and 7a via 3H-cyclobutabpyrrole derivatives such as 12.3 Nitta et al. have also reported the synthesis of 3- cyclohepta-2,4,6-trienyl-3H-azepinevia an iron carbonyl complex of ethyl 1H-azepine- 1 -carboxylate and presented the first example of 1,Shydrogen shift in the azepine ring ~ystem.~ We report here an alternative direct synthesis not only of 3H- azepines but also 2H- and 4H-azepines from methyl 2,5- 2a and methyl 3,6-di-tert-butyl-l H-azepine- 1 -carboxylates 3a by means of demethoxycarbonylation with 1,8-diazabicyclo-C5.4.0Iundec-7-ene (DBU), together with observations of the characteristic thermal behaviour of the seven-membered azatriene system.Diisopropyl and dimethyl derivatives of methyl 1H-azepine-1-carboxylates2b, c and 3b, c were also subjected to the demethoxycarbonylation described. Results and Discussion Preparation of Methyl 1H-Azepine-1-carboxylate Derivatives 2a-c and 3a-c.-The procedure for the preparation of the methyl 1H-azepine- 1 -carboxylate derivatives follows that reported by Hafner et al.'" and Lwowski et aL6 p-Di-tert- butylbenzene la, p-diisopropylbenzene 1b and p-xylene lc were heated with methyl azidoformate (0.2-0.5 equiv.) at 125OC, respectively (see Scheme 1).Careful separation of each reaction mixture by preparative medium-pressure liquid-chromato- graphy (MPLC) gave methyl 2,5-disubstituted and 3,6-disub- stituted 1H-azepine-1-carboxylates 2a-c and 3a-c in each case. Product identities were established by comparison of authentic data for 2,5-di-tert-b~tyl-,~~' 2,5-di-3,6-di-tert-b~tyl-,~.~ methyl-,8 and 3,6-dimethyl-lH-azepinesgfor 2a, 3a, 2c and 3c, respectively. The hitherto unknown 2,5-diisopropyl- and 3,6- Table 1 Calculated MNDO relative energies (AH,s)for 2H-, 3H-and 4H-azepines based on Hf of 1H-azepine H 6 7 8 1H -azepine 2H -azepine 3H -azepine 4H -azepine A~MmoPa R= H 0.0 -1 7.2 -47.5 -20.8 l.lbR= Bu' 0.0 -20.2 -1 5.9-1 6.3' The MNDO calculations were performed by complete geometry optimizations for all the compounds.For IH-azepine, a plane of symmetry passing through nitrogen and the centre of the C-4 and C-5 double bond is maintained during optimization sequence. The two relative energies were calculated for the two isomers, the structure of which are shown below, of 3,6-di-tert-butyl-3H-azepineA and B (upper for A and lower for B). 8"' Bu' Bu' H A B diisopropyl-1H-azepine- 1 -carboxylates 2b and 3b were identi- fied by comparing their 'H NMR and electronic spectra with those of the analogous 1H-azepine derivatives 2a, c and 3a, c. Demethoxycarbonylation with DBU.-A solution of methyl 1 H-azepine- 1-carboxylate derivative and DBU in dry nitrogen- purged xylene was refluxed under a nitrogen stream for 5-6 h.After cooling, the reaction mixture was introduced into a silica gel column in order to eliminate the excess of DBU and the polymeric compounds formed. From this eluent, the de- methoxycarbonylated products were obtained by preparative MPLC on a silica gel column (see Scheme 1). (a) Di-tert-butyl derivatives. The reaction of methyl 2,5-di- tert-butyl- 1 H-azepine- 1 -carboxylate 2a gave 2,5- 4a and 4,7-di- tert-butyl-3H-azepines 5a. Under similar conditions, methyl 3,6-di-tert-butyl-1 H-azepine- 1Garboxylate 3a gave 3,6-di-tert- butyl substituted 2H- 6a, 3H- 7a, and 4H-azepine 8a. The azepines 4a and 7a were identical with those previously reported.The new 4,7-di-tert-butyl-3H-azepine5a was readily R C02Me C0,Me 1a-c 2a-c 3a-c R R R+oR COpMe 4a-c 5a,b2a-c CO*Me 6a 7a-c 3a-c + a R=Bu' b R=PS c R=Me 8a Scheme 1 Reagents and conditions: i, N3C0,Me, 125 "C; ii, DBU, xylene characterized by comparing the values of the coupling constants (Hz) for its AB-quartet (J5.6 6.7) and their chemical shifts (85-H 6.14 and d6-" 6.06) with those of 4a (J6,7 8.5, 86-H6.28 and d7-H 7.28). The structure of 3,6-di-tert-butyl-2H- 6a and 3,6-di-tert- butyl-4H-azepines 8a were also elucidated by reference to the 'H and I3C NMR spectra of the previously obtained 3H- azepines 4a, 5a and 7a. Assignments of the 'H and I3C NMR spectra for all the di-tert-butylazepines (see Table 2) were based on 'H-COSY and 'H-I3C correlation (HETCOR) measure- ments.Use of N-ethoxycarbonyl derivatives instead of 2a or 3a, gave complete recovery of the starting materials no reaction having occurred. With the N-methoxycarbonyl derivatives, the reac- tion initially proceeds by effective demethylation of the methoxycarbonyl group with the strong base (DBU)," followed by decarboxylation to give 3H-azepines. (b) Diisopropyl derivatives. With methyl 2,5-diisopropyl- 1 H-azepine-1-carboxylate2b, reaction gave the 2,5-4b and 4,7- diisopropyl-3H-azepines5b, analogously to 2a, use of the 3,6- diisopropyl isomer 3b as starting material gave 3,6-diisopropyl- 3H-azepine 7b with no simultaneous formation of 2H- and 4H- azepine isomers; it thereby differed from the reaction with the correspondingly substituted di-tert-butyl- 1 H-azepine 3a.(c) Dimethyl derivatives. Labile 2,5-dimethyl- 4c and 3,6- dimethyl-3H-azepines 7c were also obtained from methyl 2,5- dimethyl-2c and methyl 3,6-dimethyl- 1 H-azepine- 1 -carboxyl- ates, 3c,respectively. In order to purify the dimethyl derivatives, the reaction mixture was passed through the silica gel column at -2 "C to prevent the degradation of the dimethyl-3H-azepine formed. Although the solution of dimethyl-3H-azepines is stable for at least 6 h even at room temperature, the solvent-free compounds became dark brown with degradation or poly- merization within 30 min at room temperature.Thermal Behaviour of Azepines 4a, 5a, 6a and 7a.-In connection with the simultaneous formation of 4a and 5a from lH-azepine 2a, we examined the possibility of thermal J. CHEM. SOC. PERKIN TRANS. 1 1994 isomerization between 4a and 5a. The reason for the formation of 4a and 5a might be considered to be a thermally allowed 13- hydrogen shift between the two. Under the demethoxycarbo- nylation conditions employed, neither 4a nor 5a gave the complementary isomers 5a and 4a, respectively. However, when a benzene solution of 5a was heated in a sealed glass tube for 2 h at 175 "C, the previously reported temperature at which the 1 $hydrogen shift occurs in a cycloheptatriene system," the isomer 4a was obtained only in 9 yield.On the other hand, the isomerization from 4a to 5a was not observed under these conditions (see Scheme 2). Earlier, we reported the results R R 4a 5a R '2 bsol; 4a R A R = BU' 4a 5a Scheme 2 Reagents and conditions: i, 175OC; ii, C6H6, 125 OC; iii, DBU, xylene of a kinetic study in which the thermal reaction of 2,4-di-tert- butyl-3a,5a-dihydro-3H-cyclobutabpyrrole 12 in benzene at 150deg;C gave 3H-azepine 4a as a single product by a disrotatory cyclobutene ring-opening mechanism. When a xylene solution of 12 and DBU was heated to reflw for 4 h, ring-opening also occurred to give the 3H-azepines 4a and 5a simultaneously in a similar ratio to that obtained from the demethoxycarbonylation reaction of 2a (see Scheme 2). This indicates that the mechanism for the isomerization of cyclobutabpyrrole 12 using DBU is different from that of the thermal isomerization.It can be considered that the cyclobutene ring-opening proceeds via an allylic DBU-deprotonated anion 13 forming the anion 9 (see Scheme 3). The same products and in a comparable ratio in both the reaction of 12 and 3a implies a common intermediate leading to 4a and 5a. The results obtained suggest that the simultaneous formation of the 3H-azepine isomers 4a and 5a is not the result of a 1,5-hydrogen shift but rather arises from the competitive prototropy of the intermediate 1H-azepine or its anion 9 under the demethoxycarbonylation conditions presented (see Scheme 3). In contrast, the 1,5-hydrogen shift was observed between 3,6- di-tert-butylazepines6a, 7a and 8a.When heated at 125 "C in toluene for 5 h, 2H- 6a or 3H-azepines 7a were converted quantitatively into an azepine mixture consisting of 2H-6a, 3H-7a and 4H-azepines 8a (1 2 :51:1 from 2H-azepine 6a or 12 :56 :1 from 3H-azepine 7a) (see Scheme 4). This result shows that the distribution of azepine isomers is proportional to their relative thermal stabilities as they interconvert via the thermally allowed 1,Shydrogen shift, although the MNDO calculated Hfvalues (see Table 1) are not reflected in the observed distribution ratios. The difference in the thermal behaviour between 2,5- or 4,7- di-tert-butylazepines and 3,6-di- tert-buty lazepines and between J. CHEM. soc. PERKIN TRANS. 1 1994 Table 2 'H (500 MHz) and I3C (125 MHz) NMR data for ring protons and carbons of azepines Ma in CDCl, c-2 c-3 C-4 C-5 C-6 ~ ~~~ ~~ ~~ ~~~ ~~ ~~ ~ 2H-fom 6a 52.2 150.6 119.1 128.6 158.7 3H-forms 4a 164.0 32.4 110.0 147.3 139.7 5a 136.4 35.1 136.8 118.6 160.1 7a 139.6 54.3 116.5 125.5 135.4 4H-fo1-m 8a 130.7 140.9 26.4 125.6 160.1 10 - 11 12 13 Scheme 3 Reagents: i, DBU; ii, H ' 6a 'I 12 .51 1 6a 7a 8a 12 . 56 1 (1 R = Bu' 7a Scheme 4 Reagents and conditions: i, toluene, 125 "C, 5 h 3,6-di-tert-butylazepineand 3,6-diisopropylazepine is not as yet clear. 2-H 3-H 4-H 5-H 6-H 7-H JIHz ~ ~~ 3.5 -6.09 6.60 -7.91 J4,56.2 J5,7 la9 -1.1 5.03 -6.28 7.28 J3,4 7.0 3.6 J6,7 8*5 6.50 1.1 -6.14 6.06 -J2,3 5-0 3.6 J5,6 6*7 6.46 0.79 5.17 6.43 -7.44 J2.3 4.8 J3.4 5.9 J3.5 1.7 J4.5 9.4 J5.1 1.9 6.73 -2.05 5.54 -8.55 J4,5 7.3 J5,7 2.1 Conclusions Efficient demethoxycarbonylation of dimethyl, diisopropyl and di- tert-butyl substituted N-methoxycarbonyl- 1 H-azepines 2a-c and 3a-c occurs when they are heated in xylene with DBU.The introduction of a bulky alkyl group into the 3H-azepine ring stabilizes the system and permits its isolation and further treatment. The evidence presented relating to the thermal behaviour of 3,6-di-tert-butyl substituted azepine indicates that the thermally allowed 1,5-hydrogen shift occurs to give an isomerized azepine mixture. Further efforts to clarify the features of the seven-membered azatriene system are underway in our laboratory. Experimental M.p.s were determined with a Yanagimoto micromelting point apparatus and are uncorrected.Silica gels HF254 (Merck) for TLC and Woelm 32-63 for preparative MPLC were used. IR spectra were recorded on a JASCO FT-IR 5000 spectro- photometer. 'H and 13C NMR were measured on a Varian XL- 200 or XL-500 spectrometer. J Values are given in Hz. Electronic spectra were recorded on a Hitachi 288 spectro- photometer. Mass spectrometry was performed on a JEOL JMS-DX300 mass spectrometer coupled to the JMA-3100 data analysis system at the Department of Chemistry, College of Liberal Arts and Science, Okayama University. Elemental analyses were performed on a Yanagimoto MT-2 CHN-corder.The molecular orbital (MNDO) calculation was carried out on a NEC ACOS-2000 computer of Okayama University Computer Center. Preparation of Methyl 2,5- and Methyl 3,6-Diisopropyl- 1 H- azepine-1-carboxylates 2b and 3b.-Methyl azidoformate (1 5 g, 0.15 mol) was added dropwise, with efficient stirring, to hot p-diisopropylbenzene lb (50 g, 0.31 mol) at 130 "C over 90 min, and the resulting solution was stirred at this temperature until the evolution of nitrogen ceased. After cooling excess of lb was removed from the brownish residue (26 g) by distillation under reduced pressure. The new residue was chromatographed (ethyl acetate-hexane 85 :15, v/v) on silica gel to give a yellow oil (1 1.5 g).From 5.0 g of the yellow oil, lH-azepines 2b (950 mg, 6.5) a pale yellow oil (Found: C, 71.5; H, 9.2; N, 6.0. C1,H2,NO2 requires C, 71.5; H, 9.0; N, 5.95); v,,,(neat)/cm-' 1722, 1648 and 1635; A,,,(cyclohexane)/nm 2 15 (log 4dm3 mol-' cm-' 4.27) and 292 (3.20); 6,(200 MHz, CDCl,) 1.10 (12 H, br d, J 7.2), 2.39 (1 H, hept, J7.2), 2.89 (1 H, br hept, J7.2), 3.62 (3 H, s) and 5.8 (4 H, m); m/z 235 (M') and 220, and 3b (790 mg, 5.4), a pale yellow oil (Found: C, 71.7; H, 9.3; N, 6.0. C14H21N02requires C, 71.5; H, 9.0; N, 5.95); v,,,(neat)/cm-' 1722, 1665 and 1637; A,,,(cyclohexane)/nm 215 (log 4dm3 mol-' cm-' 4.30) and 240 (sh, 3.40); dH(200 MHz, CDCl,) 1.04 (12 H, d, J 7.2), 2.37 (2 H, hept, J 7.2), 3.67 (3 H, s), 5.71 (2 H, br s) and 6.07 (2 H, s); m/z 235 (M') and 220, were obtained by means of MPLC using ethyl acetate-hexane (1 : 10) as eluent.Synthesis of 2,5-and 4,7-Di-tert-butyl-3H-azepines4a and 5a.--A solution of 1H-azepine 2a (2.0 g, 7.6 mmol) and DBU (12 g, 78 mmol) in nitrogen-purged dry xylene (12 cm3) was refluxed under a nitrogen stream for 6 h. After cooling, the reaction mixture was introduced into a silica gel column and eluted with ethyl acetate-hexane (1 :4). The eluent was concentrated and chromatographed again on silica gel (Woelm 32-63) by MPLC to give 3H-azepines 4a (843 mg, 54), colourless needles, m.p. 20.5-21 "C, and 5a (343 mg, 22), colourless needles, m.p. 4142 "C (Found: C, 82.0; H, 1 1.1; N, 7.0. C14H,,NrequiresC,81.9;H,11.3;N,6.8); v,,,(KBr)/cm-' 1595 (EN); A,,,(EtOH)/nm 237 (log amp;/dm3 mol-' cm-' 3.76); 6,(500 MHz, CDCl,) 1.10 (1 H, br s), 1.13 (9 H, s), 1.20 (9 H, s), 3.60 (1 H, br s), 6.06 (1 H, d, J 6.7), 6.14 (1 H, d, J 6.7) and 6.50(1 H, t, J5.0);6,(125 MHz, CDCl,) 29.5 (q), 29.7 (q),35.1 (t), 35.2 (s), 36.4 (s), 108.9 (d), 118.6 (d), 136.4 (d), 136.8 (s) and 160.1 (s).Synthesisof 3,6-Di-tert-butyl-2H-, 3H- and4H-azepines 6a, 7a and 8a.-Similarly, a solution of 1H-azepine 3a (2.74 g, 10.4 mmol) and DBU (15.8 g, 104 mmol) in nitrogen-purged dry xylene (17 cm3) gave 3H-azepine 7a (988 mg, 46) as colourless prisms, m.p. 57.5-58.5 "C, 4H-azepine 8a (27 mg, 1.3), a pale J. CHEM. soc. PERKIN TRANS. 1 1994 Synthesis of 3,6-Diisopropyl-3H-azepine7b.-A solution of 1H-azepine 3b (230 mg, 0.98 mmol) and DBU (1.7 g, 110 mmol) in nitrogen-purged dry xylene (2 cm3) was refluxed for 5 h, after which the reaction mixture was treated as described before.MPLC gave 3H-azepine 7b (74 mg, 43), as a pale yellow oil (Found: C, 80.1; H, 11.0; N, 7.7. C12H,,N requires C, 81.3; H, 10.8; N, 7.9); v,,,(neat)/cm-' 1583 (GN); A,,(EtOH)/nm 230(log 4dm3 mol-' cm-' 3.61) and 266 (sh, 3.44);6,(500 MHz, CDCl3)0.85(1H,m),1.08(3H,d,J6.8),l.ll(3H,d,J6.8),1.12 (3 H, d, J6.8), 1.18 (d, 3 H, J6.8), 2.1 3 (1 H, m), 2.59 (1 H, hept, J 64, 5.07 (1 H, dd, J 9.1 and 5.7), 6.27 (1 H, ddd, J 9.1, 1.7 and 1.7), 6.30 (1 H, d, J 4.9) and 7.32 (1 H, d, J 1.7); 6,( 125 MHz, CDC1,) 20.5 (q),20.8 (q), 23.4 (q), 23.7 (q), 28.4 (d), 33.9 (d), 51.9 (d), 118.1 (d), 125.7 (d), 136.8 (s), 136.9 (d) and 139.7 (d).Synthesis of 2,5-Dimethyl-3H-azepine 4c.-The dark brown reaction mixture obtained from the reaction of 1H-azepine 2c (143 mg, 0.80 mmol) and DBU (1.21 g, 8.0 mmol) was heated to reflux in nitrogen-purged dry xylene (2 cm3) solution for 5 h. The reaction mixture was cooled and introduced into a silica gel column, which was operated in a refrigerator room maintained at -2 "C, and eluted with ethyl acetate-hexane (1 : 4). Evapor- ation at 0deg;C of the eluent under reduced pressure gave a labile 3H-azepine 4c (43 mg, 44), as a pale yellow oil; v,,(neat)/cm-' 1605 (GN); A,,,(EtOH)/nm 235 (log 4dm3 mol-' cm-'3.53) and 250 (3.55); 6,(500 MHz, CDCl,) 1.88 (3 H, s), 2.0 (2 H, br), 2.12 (3 H, s), 4.99 (1 H, t, J6.8), 5.99 (1 H, d, J 8.3) and 7.15 (1 H, d, J 8.3); 6,(125 MHz, CDCl,) 21.0 (q),20.9 (q), 26.3 (q), 37.2 (t), 112.5 (d), 119.2 (d), 135.5 (d), yellow oil (Found: C, 82.1; H, 11.3; N, 6.7.C14H2,N requires C, 81.9; H, 11.3; N, 6.8); v,,(neat)/cm-' 1603 (GN);139.7 (s) and 151.6 (s). A,,(EtOH)/nm 241 (log amp;/dm3 mol-' cm-' 3.37) and 313 (3.09); 6,(500 MHz, CDClJ 1.10 (18 H, s), 2.05 (2 H, d, J7.3), 5.54 (1 H, dt, J2.1 and 7.3), 6.73 (1 H, s) and 8.55 (1 H, d, J2.1); 6,(125MH~,CDC1,)26.4(t),29.5(q),29.8(q),33.7(~),34.6(~), 125.6 (d), 130.7 (d), 140.9 (s) and 160.1 (s), and 2H-azepine 6a (241 mg, 11) as colourless plates, m.p. 68.5-69 "C (Found: C, 81.9; H, 11.55; N, 6.8. C,,H,,N requires C, 81.9; H, 11.3; N, 6.8); v,,,(KBr)/cm-' 1620 (GN); A,,,(EtOH)/nm 246 (logamp;/dm3 mol-' cm-' 3.67) and 302 (3.38); 6,(500 MHz, CDC1,) 1.17 (9 H, s), 1.22 (9 H, s), 3.50 (2 H, br), 6.09 (1 H, d, J 6.2), 6.60 (1 H, dd, J6.2 and 1.9) and 7.91 (1 H, d, J 1.9);6,(125 MHz, CDCl,) 29.3 (q), 30.5 (q), 34.8 (s), 35.7 (s), 52.2 (t), 119.1 (d), 128.6 (d), 150.6 (s) and 158.7 (s) in this sequence.Synthesis of 2,5- and 4,7-Diisopropyl-3H-azepines4b and 5b.-A solution of 1 H-azepine 2b (460 mg, 2.0 mmol) and DBU (3 g, 20 mmol) in nitrogen-purged dry xylene (4 cm3) was refluxed under a nitrogen stream for 5 h and then worked up by the above described treatment for 4a and 5a to give 3H-azepines 4b (157 mg, 45), a pale yellow oil (Found: C, 81.1; H, 10.5; N, 7.75.C,,H,,N requires C, 81.3; H, 10.8; N, 7.9); v,,(neat)/cm-' 1610 (CkN); A,,(EtOH)/nm 237 (log 4dm3 mol-' cm-' 3.59) and 260 (3.62); 6,(500 MHz, CDCl,) 1.1 (1 H, m), 1.02 (6 H, d, J6.8), 1.11 (6 H, d, J6.8), 2.43 (1 H, hept, J 6.8), 2.56 (1 H, hept, J6.8), 4.93 (1 H, t, J6.6), 6.09 (1 H, d, J 8.4) and 7.25 (1 H, d, J8.4); 6,(125 MHz, CDCl,) 21.0 (q), 33.4 (d), 33.8 (t), 37.2 (d), 110.1 (d), 116.8 (d), 140.0 (s), 145.0(s) and 160.5(s), and 5b (47 mg, 13), a pale yellow oil (Found: C, 81.1; H, 10.7; N, 7.8. C,,H,,N requires C, 81.3; H, 10.8; N, 7.9); v,,(neat)/cm-' 1591 (EN); A,,(EtOH)/nm 238 (log 4dm3 mol-' cm-' 3.88) and 280sh (3.45); 6,(500 MHz, CDC1,) 1.O (1 H, m), 1.06 (6 H, d, J6.8), 1.13 (6 H, d, J6.8), 2.49 (1 H, hept, J 6.8), 2.64 (1 H, hept, J6.Q 3.4 (1 H, br), 5.99 (1 H, d, J 6.3), 6.07 (1 H, d, J6.3) and 6.49 (1 H, t, J4.9); 6,(125 MHz, CDCl,) 22.2 (q), 22.3 (q), 34.7 (d), 35.6 (d), 36.1 (t), 110.8 (d), 120.0 (d), 134.1 (s), 136.6 (d) and 157.7 (s), were obtained.Synthesis of 3,6-Dimethyl-3H-azepine 7c.-A solution of 1H-azepine 3c (103 mg, 0.56 mmol) and DBU (860 mg, 5.7 mmol) in nitrogen-purged dry xylene (2 cm3) when treated as described above gave the 3H-azepine 7c (17.1 mg, 25), as a pale yellow oil; v,,(neat)/cm-' 1605 (EN); A,,,(EtOH)/nm 232 (log 4dm3 mol-' cm-' 3.64) and 250 (3.49); dH(500 MHz, CDCl,) 1.2 (1 H, m), 1.52 (3 H, d, J6.5), 2.05 (3 H, s), 4.88 (1 H, dd, J8.9 and 5.3), 6.13 (1 H, dd, J8.9 and 1 A), 6.20 (1 H, d, J6.2) and 7.29 (1 H, s);a,( 125 MHz, CDC1,) 15.9 (q), 21.1 (q), 38.8 (d), 120.6(d), 126.5(d), 128.4(d), 139.1 (s)and 141.7(s),acompound more labile than 4c.Reaction of 2,4-Di-tert-butyl-3a,5a-dihydro-3H-cyclobuta-blpVrrole 12 with DBU.-A solution of 2,4-di-tert-butyl- 3a,5a-dihydro-3H-cyclobutabpyrrole 12 (57 mg, 0.28 mmol) and DBU (100 mg, 0.66 mmol) in dry xylene (1 cm3) was refluxed under a nitrogen stream for 4 h. After cooling, a similar procedure to the demethoxycarbonylation of 2a gave 3H-azepines 4a (30 mg, 52) and 5a (1 0 mg, 18). Thermal Isomerization Reaction of 3,6-Di-tert-butyl-2H- and 3H-azepines 6a and 7a.-The respective xylene (1.5 cm3) solutions of 2H-azepine 6a (100 mg, 0.49 mmol) and 3H- azepine 7a (100 mg, 0.49 mmol) were refluxed for 5 h under a nitrogen stream, and the resulting reaction mixtures were chromatographed on silica gel (Woelm 32-64) by MPLC.Compound 6a and 7a gave mixtures of 6a (18 mg), 7a (76 mg) and 8a (1.5 mg), and 6a (17 mg), 7a (78 mg) and 8a (1.4 mg), respectively. Acknowledgements We thank the SC-NMR Laboratory of Okayama University for the 500 and 200 MHz 'H NMR and 125 and 50 MHz I3C NMR measurements. J. CHEM. soc. PERKIN TRANS. 1 1994 References 1 (a)K. Hafner and C. Konig, Angew. Chem., 1963,75,89; K. Hafner, Angew. Chem., Int. Ed. Engl., 1964, 3, 165; (b) E. Vogel, H. J. Altenbach, J. M. Drossard, H. Schmickler and H. Stegelmeier, Angew. Chem., Int. Ed. Engl., 1980,19, 1016; (c)J. Kao, J. Comput. Chem., 1988,9,905. 2 M. J. S. Dewar and W. Thiel, J. Am. Chem. SOC., 1977,99,4899. 3 K. Satake, H. Saitoh, M. Kimura and S. Morosawa, J. Chem. SOC., Chem. Commun., 1988,1121; K. Satake, H. Saitoh, M. Kimura and S. Morosawa, Heterocycles, 1994,38,769. 4 M. Nitta, K. Shibata and M. Miyano, Heterocycles, 1989, 29, 253. 5 Preliminary communication of this work: K. Satake, R. Okuda, M. Hashimoto, Y.Fujiwara, I. Watadani, H. Okamoto, M. Kimura and S. Morosawa, J. Chem. SOC., Chem. Commun., 1991,1154. 6 W.Lwowski, T. J. MericichandT. W. Mattingly, J.Am. Chem. SOC., 1963,85,1200. 7 T. Kumagai, K. Satake, K. Kidoura and T. Mukai, Tetrahedron Lett., 1983,24,2215. 8 J. M. Photis, J. Heterocycl. Chem., 1970, 7, 1249; M. Mitani, T. Tsuchida and K. Koyama, Tetrahedron Lett., 1974, 1204. 9 L. A. Paquette, D. E. Kuhla, J. H. Barrett and R.J. Haluska, J. Org. Chem., 1969,34,2866. 10 E. J. Parish and D. M. Miles, J. Org. Chem., 1973,38, 1223. 11 T. Nozoe, K. Takahashi and H. Yamamoto, Bull. Chem. SOC. Jpn., 1969,42,3277. Paper 4/00709C Received 4th February 1994 Accepted 7th March 1994
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