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Photochemistry of4,6-Diazido-3-methylisoxazolo[4,5-c]pyridine: aConvenient Entry to 3-Methylisoxazolo[1,3]diazepineSystems†

 

作者: Donato Donati,  

 

期刊: Journal of Chemical Research, Synopses  (RSC Available online 1997)
卷期: Volume 0, issue 5  

页码: 170-171

 

ISSN:0308-2342

 

年代: 1997

 

DOI:10.1039/a608413c

 

出版商: RSC

 

数据来源: RSC

 

摘要:

N N O Me N3 N3 N N O Me Cl N3 N N O Me Cl N N N N O Me N N N N N OMe N O Me 4a,b R = H, Ac N N R 1 NR 3 2a OMe MeO 2b 170 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 170–171† Photochemistry of 4,6-Diazido-3-methylisoxazolo- [4,5-c]pyridine: a Convenient Entry to 3-Methylisoxazolo[1,3]diazepine Systems† Donato Donati, Stefania Fusi and Fabio Ponticelli* Istituto di Chimica Organica, Universit`a di Siena, pian dei Mantellini, 44, 53100 Siena, Italy UV irradiation of 4,6-diazido-3-methylisoxazolo[4,5-c]pyridine in methanol gives the 3-methylisoxazolo-1,3-diazepine derivatives 3,4 by nitrogen loss and solvent addition.Following our interest on the photochemistry of heterocycles, 1 we focused our attention on diazido-isoxazolopyridines, in view of the possibility of rearrangement of the isoxazole system2 and fragmentation of the azide moiety.3 In addition, cross-over photoreactions involving both processes might be expected. The photochemistry of aromatic azides has been largely investigated as a useful access to sevenmembered aza-heterocycles.3 However, no data have been reported on the photochemical behaviour of a,ap-diazidopyridines (simple or with condensed rings), in spite of the potential synthetic interest in obtaining larger polyazaheterocyclic rings.Reaction of 4,6-dichloro-3-methylisoxazolo[4,5-c]pyridine4 with an excess of sodium azide gave the 4,6-diazido derivative 1 in good yield. When an equivalent amount of sodium azide was used, we obtained the diazide 1 and the unreacted dichloroisoxazolopyridine.Only a trace of the 4-azido- 6-chloro-3-methylisoxazolo[4,5-c]pyridine 2 was formed, as indicated by the NMR spectrum of the reaction mixture. Compound 2 can be easily prepared from the corresponding 4-hydrazino derivative4 and nitrous acid, the product existing in the solid state as the tetrazole tautomer 2b, whereas the azide form 2a is present in solution. In fact, only in the IR spectrum of a chloroform solution of this compound did we find a strong band at 2135 cmµ1, attributable to the stretching of the N3 group.Also, compound 1 exists in solution mainly in the diazide form, since the 1H and 13C NMR and UV spectra (the last both in CHCl3 and in methanol) are very similar to those of 2a. UV irradiation of 1 in methanol gave two main products, arising from 1 through the loss of one or two molecules of nitrogen followed by the addition of one or two molecules of the solvent.NMR and mass spectral analysis of both compounds did not allow any definitive conclusion about their structures. The complete configurational assignment of the isoxazolotetrazolodiazepine 3 was performed via X-ray crystallographic analysis (Fig. 1), using a crystal obtained by slow evaporation of an ethereal solution of this compound. In spite of several attempts using different solvents, we were unable to obtain well formed crystals of compound 4a.However, acetylation of 4a with acetyl chloride–triethylamine gave the diacetyl derivative 4b, which from cyclohexane –diethyl ether afforded crystals suitable for X-ray crystallographic analysis (Fig. 2). The formation of the diazepines 3 involves elimination of N2 from the azido group in position 4, ring enlargement to a cyclic carbodiimide3 and methanol addition. Similarly, in order to explain the formation of 4a, we may suppose N2 elimination from the azido group in position 6, ring enlargement and methanol addition, but in this case, the intermediate 4-azido diazepine decomposes and the resulting nitrene adds methanol without a second ring insertion.*To receive any correspondence (E-mail: donati@unisi.it). †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). ‡Atomic coordinates, thermal parameters, and bond lengths and angles have been deposited at the Cambridge Crystallographic Data Centre (CCDC).See Instructions for Authors, J. Chem. Research (S), 1997, Issue 1. Any request to the CCDC for this material should quote the full literature citation and the reference number 423/4. Scheme 1 Fig. 1 X-Ray structure of compound 3, with 30% probability thermal ellipsoids Fig. 2 X-Ray structure of compound 4b, with 30% probability thermal ellipsoidsJ. CHEM. RESEARCH (S), 1997 171 It is to be noted that, unexpectedly, the isoxazole ring is not involved in these photochemical rearrangements. These results show that this reaction is a good entry to the previously unknown isoxazolo[4,5-d]- and -[4,5-e]-[1,3]diazepine systems.Taking into account the easy opening of the isoazole moiety and the versatile addition on the intermediate carbodiimides, it is possible to prepare also several diazepine derivatives, a class of heterocycles with potential biological interest.5 Experimental IR spectra were obtained, unless otherwise stated, for KBr discs with a Perkin-Elmer 782 spectrometer. 1H and 13C NMR spectra were recorded for solutions in CDCl3 on a Bruker AC 200 instrument operating at 200 MHz for 1H and at 50 MHz for 13C. Chemical shifts are given in ppm relative to internal SiMe4. Electronimpact mass spectra (70 eV) were recorded on a VG 70 250S instrument. Photochemical reactions were carried out with a medium-pressure mercury immersion lamp (125 W) filtered and cooled with copper(II) sulfate solution (30 g dmµ3; cut off 300 nm); nitrogen was constantly bubbled through the irradiated solution.Diffractometer data were collected on a Siemens P4 diffractometer, at room temperature (293�2 °K), using graphite monochromated MoKa radiation (l=0.7107) with the w-scan technique and corrected for Lorentz and polarization effect, no absorption corrections. The structures were solved by direct methods and refined by full-matrix least-squares on F2 using the program packages SHELXTL-PC6 and SHELXL93.7‡ 4,5-Diazido-3-methylisoxazolo[4,5-c]pyridine 1.·Reaction of 4,6-dichloro-3-methylisoxazolo[4,5-c]pyridine4 with an excess of sodium azide in propan-1-ol–water, 5:1 at 60 °C for 24 h gave compound 1 as a colourless solid, yield 88%, mp 71–72 °C (from ethanol–water); vmax/cmµ1 3095 (CH), 2230, 2200, 2135 (N3), 1610, 1590 and 1450; vmax/cmµ1 (CHCl3), 2180, 2090; dH 2.56 (3 H, s, Me), 6.59 (1 H, s, 7-H); dC 11.0 (Me), 90.7 (C-7), 108.1 (C-3a), 149.0 (C-4), 153.6 (C-6), 153.8 (C-3), 171.1 (C-7a); m/z 216 (M+, 34%), 160 (6), 107 (87), 79 (34), 67 (100) (Found: C, 39.0; H, 1.9; N, 51.6.C7H4N8O requires C, 38.9; H, 1.9; N, 51.8%). 5-Chloro-9-methylisoxazolo[4,5-c][1,2,3,4]tetrazolo[1,5-a]pyridine 2b.·6-Chloro-4-hydrazino-3-methylisoxazolo[4,5-c]pyridine4 (10 mmol) dissolved in 3 M hydrochloric acid (30 cm3) was treated with sodium nitrite (10 mmol) and the mixture was repeatedly extracted with diethyl ether.Solvent evaporation and sublimation in vacuo gave compound 2b as a colourless solid, yield 62%, mp 95–96 °C; vmax/cmµ1 3060 (CH), 1650 (C�N), 1580, 1515; vmax/cmµ1 (CHCl3) 2230, 2135; dH 2.59 (3 H, s, Me), 7.20 (1 H, s, 6-H); dC 11.2 (Me), 102.2 (C-6), 109.8 (C-9a), 149.7 (C-10), 149.8 (C-5), 153.9 (C-9), 170.4 (C-6a); m/z 209/211 (M+, 42/14%), 181/183 (12/4), 146 (29), 114 (22), 88 (43), 67 (100) (Found: C, 39.9; H, 1.9; N, 33.6.C7H4ClN5O requires C, 40.1; H, 1.9; N, 33.4%). Irradiation of Compound 1.·Compound 1 (2 mmol) in methanol (100 ml) was irradiated until about half of the starting material had disappeared (TLC). Solvent evaporation and column chromatography on silica gel [chloroform–methanol 95:5 (v/v)] gave, after the unreacted compound 1 (0.8 mmol), 5-methoxy-7-methyl- 10H-isoxazolo[5,4-f][1,2,3,4]tetrazolo[1,5-c][1,3]diazepine 3 as a white solid, yield 15%, mp 155–156 °C (from diethyl ether); vmax/ cmµ1 1700 (C�N), 1625, 1590, 1440; dH 2.34 (3 H, s, Me), 4.20 (3 H, s, OMe), 4.65 (2 H, s, CH2); dC 8.9 (Me), 22.7 (C-10), 56.9 (OMe), 121.2 (C-6a), 141.3 (C-5), 150.5 (C-10a), 150.9 (C-9a), 158.4 (C-7); m/z 220 (M+, 10%), 191 (3), 151 (14), 136 (9), 123 (46), 108 (100), 83 (18), 66 (69) (Found: C, 43.8; H, 3.7; N.C8H8N6O2 requires C, 43.6; H, 3.7; N, 38.2%). Crystal Data for 3: C8H8N6O2, Mr=220.20, orthorhombic, space group Fdd2, a=17.244(3), b=34.136(7), c=6.802(1) Å, V=4003.9(12) Å3, Z=16, Dc=1.461 Mg mµ3, F(000)=1824, m=0.112 mmµ1, crystal dimensions 0.15Å0.20Å0.65 mm. 1565 unique reflections were collected. Non-hydrogen atoms were refined as anisotropic, hydrogen atoms were located in the difference- Fourier map and refined as isotropic. Final R1=0.042, wR2=0.091 for 176 parameters. Largest difference peak in the Fourier map was 0.207 e.ŵ3, maximum shift/esd=0.425 for U11 of H16A. Further elution afforded 6,8-dimethoxy-3-methyl-5,6-dihydro- 4H-isoxazolo[4,5-e][1,3]diazepin-4-imine 4a as a yellowish solid, yield 25%, mpa330 °C (from benzene–hexane); vmax/cmµ1 3400 (NH), 3150br (NH), 1680 (C�N), 1635, 1610, 1550, 1520; dH 2.48 (3 H, s, Me), 3.57, 3.69 (each 3 H, 2 s, 2ÅOMe), 5.63 (1 H, s, CH); dC 11.2 (Me), 54.8 (6-OMe), 55.5 (8-OMe), 82.5 (C-8), 106.2 (C-3a), 155.0 (C-4), 155.7 (C-6), 158.9 (C-3), 172.4 (C-8a); m/z 224 (M+, 47%), 223 (16), 209 (59), 194 (70), 193 (100), 181 (79), 168 (28), 136 (40), 122 (18), 107 (26), 81 (32) (Found: C, 47.9; H, 5.2; N, 25.2.C9H12N4O3 requires C, 48.2; H, 5.4; N, 25.0%). N - (7 - Acetyl- 6,8 - dimethoxy- 3 - methyl- 7,8 - dihydro- 4H - isoxazolo[4,5 - e] [1,3]diazepin-4-ylidene)acetamide 4b.·To a solution of compound 4a (1 mmol) in anydrous dichloromethane (16 cm3) and triethylamine (0.3 cm3) acetyl chloride (0.28 cm3) was added. After 30 min, water was added and the organic layer was washed with water and evaporated to give, after column chromatography on silica gel with diethyl ether–hexane 3:1 (v/v), compound 4b as colourless crystals, yield 78%, mp 141–142 °C (from cyclohexane–diethyl ether); vmax/ cmµ1 1717 (CO), 1709 (CO), 1660, 1640, 1605, 1435; dH 2.21, 2.32 (each 3 H, s, 2ÅMeCO), 2.48 (3 H, s, Me), 3.54, 3.93 (each 3 H, 2 s, 2ÅOMe), 6.74 (1 H, s, CH); dC 11.6 (Me), 22.9, 25.0 (2ÅMeCO), 76.8 (C-8), 112.6 (C-3a), 144.0 (C-4), 149.5 (C-6), 159.5 (C-3), 167.5 (C-8a), 169.2, 185.8 (2 CO); m/z 308 (M+, 10%), 293 (38), 251 (100), 225 (36), 219 (34), 191 (18), 43 (79) (Found: C, 50.4; H, 5.1; N, 18.2.C13H16N4O5 requires C, 50.6; H, 5.2; N, 18.2%). Crystal data for 4b. C13H16N4O5, Mr=308.30, monoclinic, space group C2/c, a=16.580(1), b=11.750(1), c=16.664(1) Å, b=101.05(1)°, V=3109.1(4) Å3, Z=8, Dc=1.317 Mg mµ3, F(000)=1296, m=0.103 mmµ1, crystal dimensions 0.20Å0.45Å 0.60 mm. 5314 reflection were collected with 4464 unique reflections (Rint=0.0160). Non-hydrogen atoms were refined as anisotropic. Hydrogen atoms were located in the difference Fourier map and refined as isotropic with a common displacement parameter free to refine for the methyl groups.Final R1=0.051, wR2=0.138 for 249 parameters. Largest difference peak in the Fourier map was 0.232 e ŵ3, maximum shift/esd=0.103 for y/b of H17C. The availability of the mass spectrometer and of the X-ray diffractometer in the ‘Centro di Analisi e Determinazioni Strutturali’ of the University of Siena is gratefully acknowledged.This work was supported by the ‘Ministero dell’Universit` a e della Ricerca Scientifica e Tecnologica’ (MURST). Received, 16th December 1996; Accepted, 3rd February 1997 Paper E/6/08413C References 1 D. Donati, S. Fusi and F. Ponticelli, Tetrahedron Lett., 1996, 37, 5783 and references cited therein. 2 D. Donati, F. Ponticelli, P. Bicchi and M. Meucci, J. Phys. Chem., 1990, 94, 5271. 3 A. Reisinger and C. Wentrup, Chem. Commun., 1996, 813 and references cited therein; J. C. Hayes and R. S. Sheridan, J. Am. Chem. Soc., 1990, 112, 3879; C. J. Shields, D. R. Chrisope, G. B. Schuster, A. J. Dixon, M. Poliakoff and J. J. Turner, J. Am. Chem. Soc., 1987, 109, 4723; C. Wentrup and H. W. Winter, J. Am. Chem. Soc., 1980, 102, 6161; Y. Z. Li, J. P. Kirby, M. W. George, M. Poliakoff and G. B. Schuster, J. Am. Chem. Soc., 1988, 110, 8092. 4 G. Adembri, A. Camparini, F. Ponticelli and P. Tedeschi, J. Chem. Soc., Perkin Trans. 1, 1975, 2190. 5 R. I. Fryer and A. Walser, in Bicyclic Diazepines, ed. R. I. Fryer, John Wiley, New York, 1991, pp. 130–131. 6 G. M. Sheldrick, SHELXTL-PC, Siemens Analytical X-Ray Instruments, Madison, Wisconsin, USA, 1990. 7 G. M. Sheldrick, SHELXL93, Program for Crystal Structure Solution, University of Gottingen, Germany, 199

 



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