975J. CHEM. soc. PERKIN TRANS. i 1993 Synthesis of Met hano- br idged Tet rade hyd rod iaza221ann u lene and Related Compounds Hiroyuki Higuchi,a Hiroyuki Yamamoto,8 J6ro Ojima +A and Gaku Yamamoto *r6 a Department of Chemistry, Faculty of Science, To yama University, Gofuku, Toyama 930, Japan Department of Chemistry, Faculty of Science, The University of Tokyo, Bunkyo-ku, Tokyo I 13,Japan Synthesis of 9,22-diethoxy-l3,18-dimethyl-l4,15.16,17-tetradehydro-2,7-methano-l,8-diaza22-annulene (9,22-diethoxy-l3,18-dimethyl-2,7-methano-l,8-diazacyclodocosa-2,4,6,8,lO,12,18,2O,-22-nonaene-14.16-diyne), is described. Examination of 'H NMR and electronic spectra indicates that the diaza22annulene shows no ring current effect but does show polyolefinic character despite the potential diatropic 22n-electron system.Attempts to prepare the higher analogues, diaza 24 -and -26annulenes are also described. In previous papers, we have reported the synthesis of a series heteroannulene with two heteroatoms so far obtained in which of monocyclic tetradehydroaza-annulenes2, higher vinylogues both heteroatoms replace carbon atoms of the annulene of pyridine, starting from a series of the tetradehydro-perimeter.'j annulenones 1,' and showed the alternation of the tropic nature between 4n + 21x- and 4n~-electron systems in compounds 2 with 14-to 22-membered rings.2 Results and Discussion The systematic synthesis of aza-annulenes 2 starting from Synthesis.-Treatment of the tetradehydromethanoC20)an-the annulenones 1 involved essentially (i) preparation of the nulenedione 3 with an excess of hydroxylamine hydrochloride corresponding oximes, (ii) Beckmann rearrangements to lac- in methanol, tetrahydrofuran (THF) and water gave the di- tams, and finally (iii) 0-alkylation of the lactams with oxime 6 in 88 yield. The appearance of only one singlet for the Meerwein's reagent.This successful sequence of reactions led hydroxy protons seemed to suggest that compound 6 existed as us to expect that starting from appropriate annulenediones, a single isomer, but the configuration was not clear at this stage. diaza-annulenes, the higher analogues of pyrimidine or pyrazine Treatment of compound 6 with phosphorus pentachloride in might be prepared. We have now realized this expectation in tetrahydrofuran (THF) caused double Beckmann rearrange- practice. Since the methano-bridge had been found to ments to give the dilactam 7 (28).The structure of compound contribute to keeping the annulene perimeter planar in our 7 was assigned as indicated on the basis of its 'H NMR studies upon methano-bridged tetradehydroannulenes and spectrum (see below). Thus both amide nitrogens were directly thia-ann~lenes,~the methano-bridged annulenediones 3-5, of bound to the cycloheptatriene ring. Since the Beckmann which preparations were reported only very recently, as well as rearrangement usually proceeds so that the substituent anti to their higher analogues,' appeared to be the desirable starting the hydroxy group moves from C to N,7the OH configurations materials for synthesis of diaza-annulenes.The methano- of the dioxime 6 should be those indicated. bridged diazaC22)annulene 8 thus obtained is the largest The dioxime 9 (51), obtained from the tetradehydro- 0 OEt 1 2 /TI =1-3 m =1-3 n =1-3 n =1-3 0 20-3:m = n = 0 24-4: rn = n = 1 26-5: m = 1, n = 2 976 J. CHEM. SOC. PERKIN TRANS. I 1993 .Me 3 N Me OH 6 +EmMe OEt 8a methanoC24lannulenedione 4, consisted of an inseparable mixture of stereoisomers, as judged from the appearance of three hydroxy proton signals (see Experimental section). Beckmann rearrangement of the mixture gave the dilactam 10 (67) as a sole isolable product. The 'H NMR spectrum of compound 10 indicated that it possessed the geometry shown.Therefore the unsymmetrical structure 9 could be assigned to the main isomer of the precursor dioxime. Similarly, the dioxime 11 (77), which was obtained from the tetradehydromethanoC261 annulenedione 5,' was converted into the dilactam 12 in poor yield (18). The 'H NMR spectrum of 12 showed that 12 consisted of only one regio- isomer shown by the formula, in which the two amide moieties again had opposite orientations. The reaction of the dilactam 7 with Meerwein's reagent was slow and did not proceed to completion. The dilactam 7 reacted with a large excess of triethyloxonium tetrafluoroborate in dichloromethane for 3 days at room temperature to afford the desired tetradehydromethanodiaza22annulene 8 in a poor yield (9)with a large recovery of the substrate 7.The tetradehydromethanodiaza22annulene 8 thus ob-tained is relatively stable as a solid and in solution. The conversions of both dilactams 10 and 12 to the corresponding diazaC26)- and -28 Jannulenes, respectively, as before were attempted under several different conditions by changing the reaction temperature and reactime time. However, the reactions of compounds 10 and 12 with a large excess of triethyloxonium tetrafluoroborate did not proceed and resulted in decomposition of the substrates due to instability of both compounds 10 and 12 under the reaction conditions. It is noted that recrystallisation of the dioxime 6 and the dilactam 7 from acetone and of the dilactam 12 from methanol gave crystals containing solvent of crystallisation in a molar ratio of 1:1, respectively, as evidenced from 'H NMR spectro- scopy and elemental analyses (see Experimental section).'H and 13CNMR Spectra.-Chemical shift assignments (see Experimental section) of the olefinic protons in dilactams 7, 10 and 12 were made as follows. Broad doublet signals were assigned to the protons adjacent to a methyl group, because the broadening was due to allylic coupling to the methyl protons as 7 p'-Me OEt 8 revealed by decoupling experiments, while sharp doublets were assigned to the protons adjacent to a carbonyl group or the cycloheptatriene ring. Protons adjacent to nitrogens were easily assigned because these protons showed coupling with the NH protons.Then the proton sequence along the polyene moiety was determined by successive decoupling experiments. All the -CH=CH- moieties showed Jvic 15-16 Hz indicating an E configuration while =CH-CH= moieties had Jvic10-1 1 Hz indicating the s-trans conformation.8 Irradiation of the methyl signals caused an intensity enhancement (NOE) of the doublet signals due to the respective adjacent olefinic protons HA (and HA'), clearly indicating that HA (and HA') is located outside of the macrocyclic ring. The geometries of compounds 7,lOand 12 were therefore determined as shown by the structural formula. The 500 MHz 'H NMR spectrum of the tetradehydro- methanodiaza22annulene 8 taken in CDCl, at 26 "C is shown in Fig.l(a). Owing to the potential 22n-aromatic system of compound 8, diatropicity was expected, which would afford the signals of the inner protons (HBand the methano bridge protons) at a higher field than their normal positions and of the outer protons at a lower field. Contrary to this expectation, the HB signal appears at the lowest field, although this may partly be ascribed to the deshielding anisotropy effect of the diyne moiety. All other protons have normal chemical shifts. These features suggest that compound 8 is atropic in nature. This is in sharp contrast with the behaviour of the closely related carbocyclic analogue 13, which showed strong diatropicity with the signals of the methano bridge protons at 6 0.91 and of the methyl groups at 6 2.36.Another remarkable feature is that the two protons of the methano bridge are diastereotopic affording an AB quartet signal and the methylene protons of the ethoxy groups are also diastereotopic. This indicates that the macrocyclic ring is non- planar and the flipping of the methano bridge is slow on the NMR time scale at 26 "C. The degree of dia- or para-tropicity of a heteroannulene has been found to be much smaller than that of the corresponding carbocyclic annulene,6 and we found that the monoazaC22lan- nulene 14 showed diatropicity, though small, with the signals of the methyl groups adjacent to the diyne moiety at 6 2.10 and J. CHEM. SOC. PERKIN TRANS. I 1993 (b) OCH2CH3 I HCH2 OCH2 I II1 I""l".~ I""""' I' .'I.' 'I'..'i' I .''.1""~" 8 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.0 1.5 Fig. 1500 MHz 'H NMR spectrum of compound 8 at 26 OC: (a) in CDCI, (b)in CDC1,-CF,CO,D ( -2 :1). The peak with xis due to CHCI, OH HO-N Me 9 OH / 11 2.15.' Judging from the theoretical prediction that pyrimidine or pyrazine have similar resonance energies and thus similar tropicity to pyridine,' the present diaza compound 8 should show diatropicity to a similar extent as the monoaza compound 14.Therefore, we consider that the atropic nature of compound 8 is not due to the introduction of two nitrogen atoms into the diatropic carbocyclic 22annulene system 13,but is attribut- able to the nonplanarity of the molecular skeleton.In compound 8, the ethoxy groups must be located outside the macrocycle. Therefore compound 8 cannot assume a skeletal conformation similar to that of compound 13,which would be more planar and thus more stable than the conformation which 8 is forced to adopt. We have also studied 'H NMR spectra of compound 8 in acidic media in order to obtain information on the effect of protonation on the geometry and tropicity of this compound. Addition of one-ninth volume of CF,CO,D to the CDCl, 10 12 solution of compound 8 caused a dramatic change in the 'H NMR spectrum. Further addition of CF,CO,D showed no further change in the spectrum, suggesting that compound 8 had been completely deuteriated, yielding the dicationic species 8a. The 'H NMR spectrum of 8 in CDCl,-CF,CO,D (ca.2: 1) is shown in Fig. I(b).The signals of all the protons except for those of the bridge methylene protons shift downfield. These results might be attributable to diminished n-electron density, arising from withdrawal of electrons by deuteriation and not to any change in tropicity, although the reason of the upfield shift of the bridged methylene protons is not clear. The 13CNMR spectrum of 8 in CDC1,-CF,CO,D (ca. 2: 1) shows an intriguing behaviour. Upon changing the solvent from CDCl, to CDC13-CF3C02D, C-3/C-6, C-9/C-22 and C-1 I/ C-20 show large downfield shifts (14.5, 13.3 and 11.6 ppm, respectively), while C-lO/C-21 shifts strongly upfield (8.4ppm) together with a small upfield shift of C-2/C-7 (3.9 ppm).This 978 J. CHEM. SOC. PERKIN TRANS. I 1993 4.3 4.2 4.1 6 3.3 3.2 3.1 3.0 2.9 2.8 6 Fig. 2 Temperature-dependent 'H NMR spectra of compound 8 in CDCI,: (a)the methano bridge protons and (b)OCH, protons. On the left are the observed spectra at various temperatures ("C) and on the right are the calculated spectra with the best-fit rate constants (s-') clearly indicates that the electron density alternation occurs Flipping of the Methylene Bridge in Compound 8.411order along the macrocyclic periphery. A similar behaviour has been to obtain information on the energy barrier to the flipping of observed previously in tetradehydror 1 Slannulenone deriva- the methano-bridge, a variable-temperature 'H NMR study tives." The OCH, carbon shows a large downfield shift (1 1.2 was performed for the diazaC22lannulene 8 in CDCl, in the ppm), probably due to charge density distribution on the oxy- temperature range 26-60 "C.These spectra are illustrated in gen atoms. The methano bridge carbon shows a large upfield Fig. 2 together with the calculated spectra using the DNMR3 shift (10.7 ppm), although the origin of this shift is not clear. program.'' Rate constants were determined at three tempera- The bridge methyiene protons of compound 8 in CDC1,- tures of 43, 51 and 60 "C so that both the methano bridge and CF,CO,D at 26 "C appeared as a singlet and the methylene OCH, signals gave the same best-fit value at each temperature. protons of the ethoxy groups were also magnetically equivalent, The free energy of activation for the flipping of the methano suggesting that the flipping of the methano bridge was fast on bridge is calculated to be 17.2 kcal mol-',* while the enthalpy the NMR timescale in this medium.This may be because the and entropy of activation are unreliable because of the narrow molecular skeleton in the species 8a is more flexible than that of the neutral 8 presumably due to the increased single bond character of the original C=N bonds. * 1 cal = 4.184 J. J. CHEM.SOC. PERKIN TRANS. I 1993 300 400 500 600 1Inm Fig. 3 Electronic absorption spectra of C22lannulene 13 (----), azaC22lannulene 14 (- .-. -) and diazaC22lannulene 8 (-) in THF Me 13 range of temperature and are not presented.The methylene bridge signal of the closely related carbocyclic 22 Jannulene 13 remained singlet down to -60 0C,36and the activation energy for this process was estimated to be less than 12 kcal mol-'. Thus, this fact might support the interpretation, described above, that the molecular skeleton of the diazaC22lannulene 8 is forced to be non-planar due to the presence of the ethoxy groups. Elelectronic Spectra.-The electronic absorption spectrum, measured in THF, of the tetradehydromethanodiaza22-annulene 8 is illustrated in Fig. 3, together with those of the closely related compounds, the tetradehydrorneth-ano22annulene 133b and the tetradehydroazaC22 Jannulene 14" both of which have been confirmed to show diatro- pici ty .It is noted that these spectra are similar in shape to each other and show the three distinct absorption bands characteristic of (4n + 2)x-electron systems, as has been recognized in the spectra of carbocyclic (4n + 2)x-annulenes and dehydro-annulenes. 'This feature might be reasonably attributed to the 14 fact that all of these compounds have 22x-electron perimeters. However, as is seen clearly from Fig. 3, all the bands of the diazaC22lannulene 8 are in shorter wavelengths by ca. 80 nm than the corresponding bands of the 22annulene 13 and the aza22annuiene 14, indicating that 8 is atropic, while 13 and 14 are diatropic, which is consistent with the conclusion from 'H NMR spectroscopy. The series of the lactams 15, the precursors of the aza- annulenes 2, have been reported to show tropicity.2' In accordance with this result, their main (strongest) absorption maxima showed the same alternation in the wavelengths of the main absorption maxima between (4n + 2) and (4n)x-systems, as has already been demonstrated for monocyclic annulenes and dehydroann~1enes.l~ Here we can compare the main absorption maxima between the dilactams 10 (26J-: 290 nm) and 12 (28-:338 nm).Thus, it is evident that the main absorption maximum of (4n + 2)x-dilactarn 10 is not at a longer wavelength than that of (4n)x-dilactam 12, indicating that both of the dilactams 10 and 12 as well as the dilactam 7 are atropic, as revealed by 'H NMR spectroscopy (see Experimental section). 980 J.CHEM. SOC. PERKIN TRANS. 1 1993 Me Me 15 m =1-3 n =1-3 Experimental M.p.s were determined on a hot-stage apparatus and are uncorrected. 1R spectra were taken with a Hitachi 260-50 spectrophotometer as KBr discs and were calibrated against polystyrene; only significant maxima are described. Electronic spectra were measured in tetrahydrofuran (THF) solution and run with a Hitachi 220A spectrophotometer. Mass spectra were recorded with a JEOL JMS-D 300 spectrometer operating at 75 eV using a direct-inlet system. 'H NMR spectra at ambient temperature were recorded with a JEOL FX-90Q (90 MHz), GX-270 (270 MHz) or a Bruker AM-500 (500 MHz) spectro- meter at 89.60,270.16 or 500.14 MHz, respectively, SiMe, being used as an internal standard.J-Values are given in Hz. Assignments were clarified by the use of decoupling experiments where necessary. Variable-temperature 'H NMR measure-ments were made on an AM-500 spectrometer and the temperatures were calibrated with an ethylene glycol sample. I3C NMR spectra were recorded with a Bruker AM-500 spectrometer at 125.76 MHz, SiMe, being used as an internal standard. Chemical shifts of the protonated carbons were unambiguously assigned on the C-H COSY spectrum. Merck alumina (activity 11-111) or Daiso Gel 1001 W was used for column chromatography. Progress of all reactions was followed by TLC using Merck pre-coated silica gel. Dichloromethane was distilled over calcium hydride before use. Tetrahydrofuran (THF) was distilled from sodium benzophenone ketyl under nitrogen atmosphere before use.Organic extracts with dichloromethane or chloroform were washed with saturated aq. sodium chloride and dried over anhydrous calcium chloride prior to removal of the solvent. Solvents were evaporated under water-pump pressure. Me' Me 13,18-Dimethyl-2,7-methano-1,8-diazacyclodocosa-2,4,6,10,-12,18,20-heptaene-l4,16-diyne-9,22-dione7.-A solution of phosphorus pentachloride (600 mg, 2.88 mmol) in dry THF (32 cm3) was added dropwise to a stirred solution of dioxime 6 (109 mg, 0.31 mmol) in dry THF (20 cm3) during 30 min at -12 "C, and stirring was continued for 5 h at room tempera- ture. Then the solution was poured into aq. sodium hydrogen carbonate and the mixture was extracted with chloroform.The combined extracts were washed with brine and dried. The residue obtained after removal of the solvent was chromato- graphed on alumina (3.2 x 6 cm). The fractions eluted with 10 acetone in benzene afforded the dilactam 7 (39 mg, 28) as red cubes, m.p. 264-265 "C (decomp.) (from hexane-acetone) (Found: M', 356.1521. C,,H,,N,O, requires M, 356.1 522); L,,,/nm 290 (E 38 700), 342 (17 100) and 406sh (6900); vmax/cm-' 3260 (NH), 2180 (W),1650 (M),985 and 970 (E)-HC==CH; S,(270 MHz; CDCI,) 7.92 (2 H, s, NH), 7.29 (2 H, dd, J 15.6 and 11.0, HB), 6.75 (2 H, m, H'), 6.66 (2 H, d, J I 1.O, HA),6.49 (2 H, m, HI), 6.16 (2 H, d, J 15.6, Hc), 2.66 (2 H, s, CH,), 2.17 6 H, s, (CH,),CO and 2.04 (6 H, s, CH,) Found: C, 75.8; H, 6.1; N, 6.2.C,3H2,N,0,~(CH,),C0 requiresc, 75.4; H, 6.3; N, 6.8. 9,22-Diethoxy-13,18-dimethy1-2,7-methano-1,8-diazacyclodo-cosa-2,4,6,8,10,12,18,20,22-nonaene-14,16-diyne8.-To a stirred solution of the dilactam 7 (1 37 mg, 0.38 mmol) in dry dichloromethane (10 cm3) was added dropwise a solution of triethyloxonium tetrafluoroborate (1.90 g, 10.0 mmol) in dry dichloromethane (5 cm3)during 5 min at room temperature under argon. After stirring for a further 21 h at room temperature, further portions of the oxonium salt (each 1.10 g/3 cm3of CH,CI,) were added every 25 h. After stirring for a total 12,17-Dimethyl-2,7-methanocycloicosa-2,4,6,9,11,17,19-hepta-of 3 days, the reaction was quenched by addition of 50 ene-13,15-diyne- 1,8-dione Dioxime 6.-To a stirred solution of the tetradehydromethano20annulenedione 3 (2.50 g, 7.66 mmol) in methanol (20 cm3) and THF (460 cm3) was added in one portion a solution of hydroxylamine hydrochloride (20.0 g, 288 mmol) in water (40 cm3) at room temperature and the mixture was stirred for 1 day at 48 "C.Then a further quantity of hydroxylamine hydrochloride (40 g) in water (40 cm3) was added to the mixture and stirring was continued for a further 2 days at 48 "C. Then the mixture was poured into water and the aqueous layer was extracted with chloroform. The combined organic layers were washed with aq. sodium hydrogen carbonate, dried and concentrated. The residue was chromatographed on alumina (3.8 x 3.5 cm).The fractions eluted with 10-20 ethanol in chloroform afforded the dioxime 6 (2.39 g, 88) as yellow needles, m.p. 168-1 70 "C (decomp.) (from hexane- acetone); m/z 356 (M', 17) and 77 (100) (Found: M', 356.4); Rmax/nm243(cjdrn3 mol-' cm-' 37 000),274(30 700), 324(26 800) and 408sh (4600); vmax/cm-' 3200 (OH), 2 190 (CS), 1605 (N=C), 980 and 960 (E)-HCXH; 90 MHz; (CD,),SO 1 1.57 (2 H, s,OH), 6.94--6.( 10H,m, olefinicand7-membered-ringH),4.49 (lH,d,J12,Hb),2.086H,s,(CH,),CO,1.85(6H,s,CH3)and 1.64 (1 H, d, J 12, Ha) Found: C, 75.4; H, 6.4; N, 6.5. C23H,oN,02~(CH3)2C0requires C, 75.4; H, 6.3; N, 6.8. aqueous potassium carbonate (20 cm3) during 10 min at 3 OC. Then the mixture was poured into water and extracted with dichloromethane. The combined extracts were evaporated and the residue was chromatographed on alumina (3.2 x 7 cm).The initial fractions eluted with benzene afforded the diazaC22lan- nulene8(15 mg, 9.0) as brown needles, m.p. 149-1 50 "C (from hexane-benzene); m/z 412 (M', 100) (M, 412.5); Rmax/nm 222 (E 26 700), 285 (37 loo), 372 (7700) and 397sh (6300) and see Fig. 3; vmaX/cm-' 2170 (CK), 1635 (C=N), 1300, 1220, 1030 (a)and 960 (E)-HC==CH; 6,(500 MHz; CDCI,, 26°C) 7.03(2H,dd, J16.2and 10.8,HB),6.44(2H,d,J10.8,HA),6.14 (2 H, m, H'), 5.84 (2 H, d, J 16.2, Hc), 5.29 (2 H, m, H'), 4.19 (2 H, dq, J 10.9 and 7.1, CH,CH,), 4.12 (2 H, dq, J 10.9 and 7.1, CH2CH3),3.21 (1 H,d, J12.8,Hb),2.88(1 H,d, J12.8,Ha), 1.95 (6 H, s, CH,) and 1.29 (6 H, t, J 7.1, CH'CH,) and see Figs.1(a) and 2; 6,500 MHz; CDC1,-CF,C02D ( -2: l), 26 "C 7.29 (2 H, m, H'), 7.19 (2 H, dd, J 15.2 and 11.2, HB), 7.00 (2 H, d, J 11.2, HA), 6.94(2 H, m, H2), 6.58(2 H, d, J15.2, HC),4.75(4H, q, J 7.1, CH'CH,), 2.60 (2 H, s, CH2), 2.27 (6 H, s, CH,) and 1.63 (6 H, t, J 7.1, CH,CH,) and see Fig. l(6); 6,(125 MHz; CDCI,) 158.3 (9, C-9 and C-22), 141.0 (q, C-2 and C-7), 138.3 (t, C-12 and C-19: C-HA), 137.0 (t, C-11 and C-20: C-HB), 124.7 (t, C-4 and C-5: C-H'), 123.8 (9, C-13 and C-18), 120.0 (t, C-10 J. CHEM. SOC. PERKIN TRANS. I 1993 and C-21: C-HC), 107.7 (t, C-3 and C-6: C-HI), 82.8 and 81.2 (9, CK), 61.8 (s, CH,CH,), 43.8 (s, CH,), 22.3 (p, CH,)and 14.2 (CHZCH,); 6J125 MHz, CDCl,-CF,CO,D ( -2: l), 26 "C 171.6 (q, C-9 and C-22), 148.6 (t, C-11 and C-20: C-HB), 137.2 (t, C-12 and C-19: C-HA), 137.1 (9,C-2 and C-7), 130.3 (t, C-4 and C-5: C-H2), 122.7 (q, C-13 and C-18), 122.2 (t, C-3 and C-6: C-H'), 11 1.6 (t, C-10 and C-21: C-HC), 85.1 and 84.2 (q, Cg),73.0 (s, CH,CH3), 33.2 (s, CH,), 23.0 (p, CH,) and 14.1 (p, CH,CH,) (Found: C, 78.8; H, 6.7; N, 6.5.C,,H,,N,O, requires C, 78.6; H, 6.8; N, 6.8). The latter fractions eluted with 10 acetone in benzene afforded the recovered dilactam 7(1 03 mg). I6,2 I -Dimethyf-4,9-methanocycfotetrucosu-2,4,6,8,10,I 3,15,-21,23-nonaene-17,19-diyne-l ,12-dione Dioxime 9.-To a stirred solution of the tetradehydromethano24annulenedione 4 (1.10 g, 2.91 mmol) in methanol (30 cm3) and THF (50cm3) was added in one portion a solution of hydroxylamine hydro- chloride (12.1 g, 175 mmol) in water (20 cm3) and the mixture was stirred for 4h at 52 "C, Then the mixture was worked up as for the isolation of the compound 6.The product was chromatographed on alumina (3.2 x 4.0 cm). The fractions eluted with 4040 ethanol in chloroform afforded the dioxime 9 (623 mg, 51) as yellow microcrystals, m.p. 143-145 "C (decomp.) (from hexane-chloroform); m/z 408 (M +,6) and 51 (100) (Found: M', 408.4); A,,,/nm 230sh (E 19 500), 270 (64500),285 (60 500), 358 (29200) and 405sh (9330); vmax/ cm-' 3180 (OH), 2180 (CS), 1600 (NX) and 970 (E)-HC=CH; SH90 MHz; (CD,),SO 11.58, 1 1.48, 11.45 (1 :1:2) (2 H, s, OH), 6.93-6.42 (14 H, m, olefinic and 7-membered-ring H), 2.69 (2 H, br s, CH,) and 1.91 (6 H, s, CH,) (Found: C, 79.6; H, 6.0; N, 6.6.C,,H,,N,02 requires C, 79.4; H, 5.9; N, 6.9). 18,23-Dimethyl-5,1 0-methano- 1,13-diazacyclohexacosa-3,5,-7,9,11,15,17,23,25-nonaene-19,21-diyne-2,14-dione 10.-A solu-tion of phosphorus pentachloride (1.17 g, 5.62 mmol) in dry THF (40 cm3) was added dropwise to a stirred solution of the dioxime9 (1.15 g, 2.82 mmol) in dry THF (360 cm3) during 1 h at -18 to -15 "C. After stirring for 3 h at the same temperature, the mixture was stirred for a further 1.5 h at room temperature. Then the mixture was worked up as for the isolation of compound 7. The product was chromatographed on Daiso gel (3.6 x 8.Ocm). The fractionseluted with benzene-dichlorometh- ane (2:3) afforded the dilactam 10 (766 mg, 67) as orange needles, m.p.233-235 "C (decomp.) (from acetone-chloroforrn); m/z408 (M +, 85) and 207 (100) (Found: M +,408.4); A,,,/nm 280sh (E 45 700), 290 (46 300), 318sh (41 400) and 360 (38 600); v,,,/cm 3250 (NH), 21 80 (Cg), 1660,1620,1600 (C-, C=C)and 960 (E)-HC=CH;6,500 MHz; CDC1,-(CD,),SO (5 :l) 10.66(1 H, d, J 10.0, NH'), 8.41 (1 H, d, J 1 1.5, NH2), 7.59 (1 H, d,J15.4,Ht'),7.50(1 H,dd, J15.2and 11.5,HB),7.47(1 H,dd,J 13.8and11.5,HC'),7.22(1H,dd,J14.5andT0.0,HD),6.85(1H, dd, J 10.5and 6.2, H2), 6.81 (1 H, d, J 11.5, HA), 6.73 (1 H, d, J 11.2, HA'), 6.73-6.70 (2 H, m, H3 and H4), 6.37 (1 H, d, J 15.2, HC),6.35(1 H,d, J6.2, H'),6.27(1 H,d, J 14.5, HE), 6.13 (1 H,d, J 15.4,HD'),6.06(1 H, dd, J 13.8 and 11.2, HB), 3.40(2 H, s, CH,), 2.04(3 H, s, Me') and 1.94(3 H, s, Me") (Found: C, 79.4; H, 5.95; N, 6.6.C,,H,,N202 requires C, 79.4; H, 5.9; N, 6.9). 18,23-Dimrthyl-6,1l-methanocyclohexacosa-2,4,6,8,10,12,I5, 17,23,25-decaene-l9,21-diyne-1,14-dioneDioxime 11.-To a stirred solution of the tetradehydromethano26annulenedione 5 (1.42 g, 3.52 mmol) in methanol (40cm3) and THF (200 cm3) was added in one portion a solution of hydroxylamine hydro- chloride (4.60 g, 66 mmol) in water (8 cm3) at room temperature. The mixture was stirred for I h at 52 OC, after which a further quantity of hydroxylamine hydrochloride (7.50 g, 107 mmol) in water (5 cm3) was added and stirring was 981 continued for a further 5 h at 52°C.Then the mixture was worked up as for the isolation of the compound 6.The product was chromatographed on alumina (3.8 x 2 cm). The fractions eluted with ethanol-dichloromethane (1 :1) afforded the diox- ime 11 (1.16 g, 77) as yellow microcrystals, m.p. 1641 65 "C (decomp.) (from hexane-chloroform); m/z 432 (M +,10) and 83 (100) (Found: M+, 434.5); A,,,/nm 261 (E 50 300), 298 (82 OW), 365 (29 000) and 401sh (1 7 800); v,,,/cm-' 3185 (OH), 2180 (CK), 1600 (N=C) and 960 (E)-HC=CH; 6,90 MHz; (CD,),SO 11.40 (2 H, br s, OH), 7.08-6.22 (16 H, m, olefinic and 7-membered-ring H), 2.67 (2 H, s, CH,) and 1.93 (6 H, s, CH,) (Found: C, 80.1; H, 6.0; N, 6.2. C,9H26N,0, requires C, 80.2; H, 6.0; N, 6.45). 20,25-Dimethy1-7,12-methano-1,15-diazacyclooctacosa-3,5,7,-9,11,13,17,19,25,27-decaene-21,23-diyne-2,16-dione 12.-A sol-ution of phosphorus pentachloride (220 mg, 1.12 mmol) in dry THF (10 cm3) was added dropwise to a stirred solution of dioxime 11 (406 mg, 0.93 mmol) in dry THF (60 cm3) during 10 min at -12 "C and the solution was stirred for 4 h at -4 "C.Then the mixture was worked up as for the isolation of compound 7.The product was chromatographed on alumina (3.2 x 7 cm). The fractions eluted with chloroform afforded the dilactam 12 (73 mg, 18) as red needles, m.p. 238-240 "C (decomp.) (from methanol); m/z 434 (M , 100) (Found: M ,+ + 434.5); AmaX/nm 275 (E 22 700) and 338 (67 400); v,,,/cm-' 3240 (NH), 2180 (M),1660, 1620 (W,C=C), 990 and 950 (E)-HC==CH; 6,500 MHz; CDCI,-(CD,),SO 8.90 (1 H, br d, J 11.0, NH'), 8.13 (1 H, dd, J 14.8 and 11.4, HB),7.89(1 H, dd, J 14.3 and 11 .O, HD), 7.22(2 H,m, HE'and HF'), 7.15 (1 H, d, J 11.0, NH'), 7.06 (1 H, dd, J 13.6 and 11.0, H"), 6.97 (1 H, dd, J 13.6 and 11.4, HB'), 6.76 (1 H, m, HD'), 6.57 (1 H, m, HG'),6.54 (2H,m, H2andH3),6.50(1 H,d,JI 1.4, HA'),6.36(1 H,d,Jll.4, HA), 6.33 (1 H, m, H4), 6.12 (1 H, m, HI), 5.94( 1 H, d, J 14.3,HE), 5.81 (1 H, d, J 14.8, HC), 2.87 (2 H, br s, CH,), 1.98 (3 H, s, Meb) and 1.83 (3 H, s, Me") (Found: C, 77.1; H, 6.6; N, 5.95.C2,H,,N,0,~CH,0H requires C, 77.2; H, 6.5; N, 6.0). Acknowledgements Financial support by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan, and by grants from The Nishida Research Fund for Funda- mental Organic Chemistry and The Sumitomo Research Fund, is gratefully acknowledged.References 1 T. M. Cresp, J. Ojima and F. Sondheimer, J. Org. Chem., 1977,42, 2130; J. Ojima, Y. Shiroishi, K. Wada and F. Sondheimer, J. Org. Chem., 1980,45,3564;J. Ojima, K. Wada and M. Terasaki, J. Chem. SOC.,Perkin Trans. I, 1982, 51 and the references cited therein. 2 (a)J. Ojima, T. Nakada, M. Nakamura and E. Ejiri, Tetrahedron Lett., 1985,635; (h) J. Ojima, T. Nakada, E. Ejiri and M. Nakamura, Tetrahedron Lett., 1985,639;(c)J. Ojima, T. Nakada, E. Ejiri and M. Nakamura, J. Chem. SOC.,Perkin Trans. I, 1986.933. 3 (a) J. Ojima, E. Ejiri, T. Kato, S. Kuroda and M. Shibutani, Tetrahedron Lett., 1986,27, 2467; (b)J.Ojima, E. Ejiri, T. Kato, M. Nakamura, S. Kuroda, S. Hirooka and M. Shibutani, .I.Chem. 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Sternhell, Applications of Nuclear Mugnetic Resonance Spectroscopy in Organic Chemistry, Pergamon, London, 1969, pp. 280-304. 9 A. R. Katritzky, M. Karelson and N. Malhotra, Heterocycles, 1991, 32, 127. 10 G. Yamamoto, H. Higuchi, H. Yamamoto and J. Ojima, Bull. Chem. SOC.Jpn., 1992,65,2388. J. CHEM. SOC. PERKIN TRANS. I 1993 11 D. A. Kleier and G. Binsch, QCPE Program No. 165. 12 M. Nakagawa, Pure Appl. Chem., 1975,44, 885. 13 See P. J. Garratt and K. Grohmann, in Houhen-WeyI, Methoden der Organischen Chemie, Thieme Verlag, Stuttgart, 1972, vol. V, Id, pp. 533-535. Paper 21064226 Received 1st December 1992 Accepted 19th January 1993
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