摘要:

Diazepines. Part 29.1 A Comparison Between 6-Phenyl-and 5,7-Diphenyl-2,3-dihydrodiazepinium Salts, withComments on the Reactivity of 6-Phenyldihydro-diazepinium SaltsTowards Electrophiles. Crystal andMolecular Structures of 6-Phenyl- and 2,3-Cyclohexano-6-phenyl-2,3-dihydro-1,4-diazepinium Picrates{Douglas Lloyd,*a Hamish McNab*b and Simon ParsonsbaSchool of Chemistry, Purdie Building, University of St. Andrews, St. Andrews, Fife KY16 9ST, UKbDepartment of Chemistry,The University of Edinburgh,WestMains Road, Edinburgh EH9 3JJ, UKConjugative interaction between a 6-phenyl substituent and the vinamidinium system of a dihydrodiazepinium salt appears to beless than that observed with 5- or 7-phenyl substituents; despite this, electrophilic substitution occurs very readily in the 6-phenylgroup and comment is made on a possible mechanism.The structure of a dihydrodiazepinium ring 1 consists of adelocalised vinamidinium portion [N(4),C(5¡Ó7),N(1)], whichhas a at helical structure and whose ends are linked by adimethylene bridge that has a half-chair shape.Although the ring lacks complete cyclic conjugation, thevinamidinium system confers properties on these moleculeswhich resemble those of so-called aromatic compounds.2X-Ray structure determinations show the delocalisation ofp-electrons through the vinamidinium system.3,4,5 Electro-philic substitution takes place exclusively at C(6); NMRspectra reect an alternation of polarity along the chain,C(6) being relatively electron-rich and C(5,7) relativelyelectron-poor.6,7Phenyl groups attached to these carbon atoms can inter-act electronically with the vinamidinium system; the latterwithdraws electrons from 5,7-phenyl groups but donateselectrons to a 6-phenyl group. 6-Phenyl groups, but not 5,7-phenyl groups, undergo ready electrophilic substitution atthe para-position.8,9,10 An X-ray structure determinationon the 5,7-diphenyl derivative5 gave clear evidence of thisinterannular electronic interaction.NMR spectra of solutions of 6-phenyl- 3 and 2,3-cyclo-hexano-6-phenyl 4 salts indicate a reverse donation ofelectrons, into the phenyl ring.X-Ray studies on theirpicrate salts are reported here (for preparation see full text)(Figs. 1 and 2).Crystal Data for the 6-Phenyl Derivative.C19H20N5O8;(3) picrate, 1/2MeOCH2CH2OMe, M = 446.4, triclinic,a= 9.059(4), b =10.709(3), c= 11.703(4) A , =79.77(2) 8, = 88.17(3) 8, = 65.33(2) 8, U =1014.2 A 3,space group P1, T = 220 K, Z =2, Dcalc=1.46 g cm£¾3,F(000)= 466.15, yellow lath, 0.540.270.12 mm3,(Mo-K)= 0.11 mm£¾1.2,3-Cyclohexano-6-phenyl Derivative.C21H21N5O7; (4)picrate, M =455.43, triclinic, a= 8.295(5), b = 11.363(6),c= 11.779(7) A , =112.08(4) 8, = 91.77(5) 8, =96.65(5) 8, U = 1018.5 A 3, space group P1, T = 150 K,Z =2, Dcalc.=1.485 g cm£¾3, F(000)= 476, yellow column,0.580.230.16mm3, (Mo-K)= 0.11mm£¾1.Data Processing.Data were collected on a Stoe Stadi-4diractometer equipped with an Oxford Cryosystems low-temperature device in the range 5R2R45 8 using Mo-KX-radiation.Both structures were solved by direct methods(SIR92) and rened by least-squares, against F for 3(CRYSTALS) and F2 for 4 (SHELXTL). H-Atoms on Cwere placed in calculated positions and allowed to ride onthe parent C-atom; those on N were located in F mapsand rened freely with a common Uiso. In 3 one nitro-oxygen is disordered over 2 sites. All non-H atoms in 3 and4 were rened with anisotropic displacement parameters.For 3, R= 4.86%, Rw=4.67% for 1840 data withF> 4(F) and 306 parameters.For 4, R1 = 4.53% [basedon F and 1805 data with F> 4(F)] and wR2=11.21%(based on F2 and all 2659 data) for 312 parameters. FinalF-synthesis extrema were +0.42 and £¾0.22 e A 3 for 3 and+0.19 and £¾0.19 e A 3 for 4. Bond lengths and bond anglesare given in Tables 1 and 2 (see full text).DiscussionElectronic interaction between the vinamidinium systemand the phenyl rings in the 5,7-diphenyl cation leads to alengthening of the N(4)C(5) and N(1)C(7) bonds [meanJ.Chem. Research (S),1998, 70¡Ó71J. Chem. Research (M),1998, 0501¡Ó0525NHHNR5R6R7+NHHNR5R6R7+orNHHNR5R6R7+1 Fig. 1 X-Ray crystal structure of compound 3Fig. 2 X-Ray crystal structure of compound 4$IUPAC nomenclature: 6-phenyl-3,4-dihydro-2H-1,4-diazepin-1-iumand 3-phenyl-5a,6,7,8,9,9a-hexahydro-5H-1,5-benzodiazepin-1-iumpicrates.*To receive any correspondence.70 J. CHEM. RESEARCH (S), 19981.332 (6) A E ]5 compared to the corresponding bonds in the unsubstituted or 5,7-dimethyl cations [mean 1.306 (4)3, 1.317 (4)4].These bonds are not lengthened in the 6-phenyl cations 3 and 4 [mean 1.310 (4), 1.320 (4) A E ], indicating little interannular interaction in these cases. In the 5,7-diphenyl derivative the ipso�}ortho bonds of the phenyl groups are longer [mean 1.397 (7) A E ] than the other bonds in these rings [mean 1.375 (7) A E ], in accord with their electronic interaction with the vinamidinium system and concomitant setting up of pentadienium systems in the phenyl rings,1,5 but in the 6-phenyl cation 3 there is only a small di€erence [ipso�}ortho, mean 1.399 (5) A E ; other bonds, mean 1.387 (5) A E ].The angle between the planes of the vinamidinium system and the phenyl ring in 3 (29.72 8) resembles that between the two rings in biphenyl in solution [32 (2) 8]17 or in the gas phase [45 (10) 8]18 and in the crystalline 5,7-diphenyl cation.Van der Waals forces, which make biphenyl planar in its crystalline form, will be less in�Puential in phenyldihydro- diazepinium cations since the seven-membered ring is not itself planar and crystal packing is dominated by hydrogen bonding. The present X-ray studies indicate that, whereas electron donation from phenyl groups contributes to the ground state of 5-(7-)phenyldihydrodiazepinium salts, electron donation into a 6-phenyl group contributes little, and that such molecules are polarisable rather than polarised. This is probably not surprising.In the case of 5-(7-)phenyl deriva- tives the overall result of electron donation is a delocalisa- tion of the positive charge, whereas in a 6-phenyl derivative the overall result is a build-up of positive charge on two nitrogen atoms held relatively close to each other by the ring structure. Monocyclic dihydrodiazepinium cations undergo rapid conformational inversion in solution, but 2,3-cyclohexano- dihydrodiazepinium cations are rigid, making it of interest to compare the crystal structure of such a cation 4 with its unannelated analogue 3; hitherto no rigid fused dihydro- diazepinium cation has been examined crystallographically.Ring fusion causes little change in the bond distances in the vinamidinium system [mean CDN, 1.320 (4) A E ; mean CDC, 1.391 (4) A E ]. Electrophilic Substitution Reactions in 6-Phenyldihydro- diazepinium Salts.DThe chemical shift for the p-carbon atom of the phenyl group in the 13C NMR spectrum of 37 suggests that the extent of electron donation from the vina- midinium system into the 6-phenyl group is only small, rather less than that associated with a substituent methyl group and comparable to that caused by an acetoxy group.In contrast the 13C NMR spectrum of the 5,7-diphenyl de- rivative7 indicates that there is rather greater interaction between the phenyl groups and the vinamidinium system; the chemical shift for the p-carbon atoms indicates a with- drawal of electrons from the phenyl groups comparable to that caused by an acetyl or an ester group.This di€erence is nicely re�Pected by the X-ray studies. The unreactivity towards electrophiles of the 5,7-phenyl groups10 is also in accord, but the ease with which electrophilic substitution takes place, under mild conditions, at the para position in 3,8,9 is not predictable from the NMR and X-ray data. Electrophilic substitution (bromination, nitration) at the para position of the phenyl groups in these salts takes place very readily8,9 and must be associated with induced polaris- ation in the cation.Such reactions proceed more slowly than do similar reactions at a free 6-position.20 This is unsurprising; while formation of a -complex involves production of adiazepinium dication and loss of the vinamidinium system in both cases, in the case of the 6-phenyl cation it also involves loss of the stabilising aro- matic sextet of -electrons in the phenyl ring.Remarkably, substituents at the 2,3-positions (or at the 1,4-positions) in 6-phenyldihydrodiazepinium cations appreciably lower the rate of bromination at the para-position of the phenyl ring, although the 2,3-positions are separated by six atoms from the site of bromination.20 This anomaly has been explained by postulating that initial attack by the electrophile is at the electron-rich nitrogen atoms, followed by its migration over the -electron system to its eventual site of substitution.The present structural studies, which show little innate polaris- ation in a substituent 6-phenyl group, may thus provide some support for the concept that initial electrophilic attack does not involve the para position of that group. We thank Steven Harris for preparing 2,3-cyclohexano- 5,7-diphenyldihydrodiazepinium picrate, and the EPSRC for Rnancial support. Technique used: X-Ray di€raction Tables 1 and 2: Lists of bond lengths and bond angles for 3 and 4 Appendix: Crystal data and structure reRnement for 1 and 3 Received, 17th July 1997; Accepted, 22nd October 1997 Paper E/7/05114J References cited in this synopsis 1 Part 28, G.Ferguson, D. Lloyd, H. McNab, D. R. Marshall, B. L. Ruhl and T. Wieckowski, J. Chem. Soc., Perkin Trans. 2, 1991, 1563. 2 For a review, see D. Lloyd and H. McNab, Adv. Heterocycl. Chem., 1993, 56, 1. 3 G. Ferguson, B.Ruhl, T. Wieckowski, D. Lloyd and H. McNab, Acta Crystallogr., Sect. C, 1984, 40, 1740. 4 G. Ferguson, W. C. Marsh, D. Lloyd and D. R. Marshall, J. Chem. Soc., Perkin Trans. 2, 1980, 74. 5 D. Lloyd, G. Ferguson and B. L. Ruhl, Acta Crystallogr., Sect. C, 1991, 47, 1290. 6 D. Lloyd, R. K. Mackie, H. McNab and D. R. Marshall, J. Chem. Soc., Perkin Trans. 2, 1973, 1729. 7 D. Lloyd, R. K. Mackie, H. McNab, K. S. Tucker and D. R. Marshall, Tetrahedron, 1976, 32, 2339. 8 D. Lloyd, K. S. Tucker and D. R. Marshall, J. Chem. Soc., Perkin Trans. 1, 1981, 726. 9 D. Lloyd, C. Reichardt and M. Struthers, Liebigs Ann. Chem., 1986, 1380. 10 A. M. Gorringe, D. Lloyd, F. I. Wasson, D. R. Marshall and P. A. Dueld, J. Chem. Soc. C, 1969, 1449. 11 D. Lloyd, H. McNab and D. R. Marshall, J. Chem. Soc., Perkin Trans. 1, 1978, 1453. 12 D. Lloyd and H. McNab, J. Chem. Res. (S), 1989, 18. 17 V. J. Eaton and D. Steele, J. Chem. Soc., Faraday Trans. 2, 1973, 1601. 18 O. Bastiansen, Acta. Chem. Scand., 1949, 3, 408. 19 Y. Yokoyama, H. Uekusa and Y. Ohashi, Chem. Lett., 1996, 443. 20 A. R. Butler, D. Lloyd, H. McNab, D. R. Marshall and K. S. Tucker, Liebigs Ann. Chem., 1989, 133. J. CHEM. RESEARCH (S), 1998 71

ISSN:0308-2342    

DOI:10.1039/a705114j

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Diazepines. Part 30.1 A Comparison between the Extentof Delocalisation of Electrons in a V|namidine and itsProtonated Form. Crystal and Molecular Structure ofTwo 2,3-Dihydro-1,4-diazepinesMagnus Brisander,a Steven G. Harris,a Douglas Lloyd,*bHamish McNab*a and Simon ParsonsaaDepartment of Chemistry,The University of Edinburgh,WestMains Road, Edinburgh EH9 3JJ, UKbSchool of Chemistry, Purdie Building, University of St. Andrews, St. Andrews, Fife KY16 9ST, UKAn X-ray study of two 2,3-dihydro-1,4-diazepine bases shows that their vinamidine systems are made up of alternate single anddouble bonds, in contrast to the derivedmonocationswhich contain fully delocalised vinamidiniumstructures.X-Ray studies of a number of 2,3-dihydro-1,4-diazepiniumsalts (1) have been carried out1,2 and show clearly theextensive delocalisation of p-electrons in the vinamidiniumportion of the molecules.The salts also have chemical andspectroscopic properties typical of a delocalised system,2and they have been described as quasi-aromatic molecules.NHHN+NHHN+X¡VNHN¡E¡E1 2Calculations based on pK data suggest that the cation 1has a stabilisation energy of about 19 kcal mol£¾1 and thatthe corresponding dihydrodiazepine base 2 has a stabilis-ation energy of 12¡Ó14 kcal mol£¾1.3 This dierence is reectedin the very high basicity of dihydrodiazepines.4 NMRspectra of both the bases and cations indicate the totalequivalence of N(1) and N(4) and of C(5) and C(7) on theNMR timescale; this implies that in the bases there is insolution a very rapid transfer of a proton between the twonitrogen atoms.In order to investigate further the extent of delocalisationof electrons in the vinamidine system in a dihydrodiazepinebase an X-ray crystallographic study has been made of thetwo bases 3 and 4 (Figs. 1 and 2).NHNPhNHNPhPh3 4(both trans-fused)Good crystalline samples of dihydrodiazepine bases aredicult to obtain, partly due to their high basicity(pKa=13¡Ó14), but proved to be obtainable in the cases of 3and 4; X-ray data were available for related cations, makingrelevant comparisons possible.X-Ray studies on thesecations showed that 2,3-fused cyclohexane rings appear tohave little eect on the structure of the unsaturated portionsof the molecules and do not distort them.1 The onlyprevious X-ray studies on 2,3-dihydro-1,4-diazepine basesinvolved molecules wherein heterocyclic rings were annelatedto the vinamidine system.5,6ExperimentalThe dihydrodiazepine bases were obtained from their perchloratesalts by suspending the latter in ether and treatment with 10 Msodium hydroxide. For details see full text.Crystal Data. 6-Phenyl Derivative.C15H18N2; 3, M=226.31,orthorhombic, a=12.318(5), b=7.460(2), c= 25.860(3) A ,U =2467.4 A 3 space group Pbca, Z =8, Dcalc=1.218 g cm£¾3,F(000)=976, colourless slab 0.500.500.10mm3, (Mo-K) =0.07mm£¾1, T= 150.0(2) K.5,7-Diphenyl Derivative.C24H30N2O; 4, Me2CHOH, M=362.50, monoclinic, a= 10.1439(7), b=16.1623(9), c= 13.1187(7)A , = 94.551(5) 8, U=2144.0 A 3, space group P21/c, Z =4,Dcalc=1.123 g cm£¾3, F(000)=784, colourless block 0.450.31 0.31mm3, (Cu-K) = 0.527mm£¾1, T =220.0(2) K.Data Processing.Both data sets were collected on a Stoe Stadi-4-diractometer equipped with an Oxford Cryosystems variabletemperature device.Data for 3 were collected in the range5R2R50 8 using Mo-K radiation (=0.71073 A ) and ! £¾ scans. Both structures were solved by direct methods and rened byfull matrix least-squares against F2.H-Atoms in 3 were located inF maps and rened freely with isotropic displacement parameters;those in 4 were mostly placed in calculated positions and allowed toride on the atoms to which they are bonded. The H-atom on N(1)was located in a F map and its positional parameters renedfreely. In 4 there is a two-fold disorder in the cyclohexane ring andin the isopropanol of crystallisation and in each case the alternativecomponents were restrained to be geometrically similar.At con-vergence for 3 R1= 4.82% [based on F and 1576 data withF >4(F)] and wR2=12.50% (based on F2 and all 2146 uniquedata) for 227 parameters. For 4, R1=5.94% (2452 data) andwR2=17.22% (3141 data) for 292 parameters. The nal F extremawere 20.19 e A 3 for 3 and +0.23/£¾ 0.27 for 4. Bond lengths andbond angles are given in Tables 1 and 2 (see full text).J. Chem. Research (S),1998, 72¡Ó73J. Chem. Research (M),1998, 0526¡Ó0550Fig. 1 X-Ray crystal structure of compound 3Fig. 2 X-Ray crystal structure of compound 4 *To receive any correspondence.72 J. CHEM. RESEARCH (S), 1998Discussion There are striking di€erences in the bond structure of the bases compared to the cations. In contrast to the delocalised structure of the vinamidinium cation, the bonds in the vinamidine systems of the dihydrodiazepine bases are alter- nately single and double (see Table 3). There is, however, little di€erence between the bond angles in the bases and cations.Whereas the vinamidinium systems have bond distances characteristic of a fully delocalised p-electron system, the bonds in the vinamidine systems in the dihydrodiazepine bases alternate in length and are reminiscent of an open- chain push-pull conjugated system rather than of a deloca- lised system. For example, in two enaminals15 the bond dis- tances of the N�}CH= bonds are 1.334(2) and 1.354(2) A E and of the CH=CH bonds are 1.363(3) and 1.355(2) A E .In the bases and the cations the conjugated vinamidine and vinamidinium moieties are both in the form of shallow helices; there is very little di€erence between them in their deviations from planarity, e.g. for 3 (base), deviation from planarity= 0.078 A E , in the cation derived from 3 0.082 A E . Thus the di€erence in their bond structures cannot be ascribed to any steric interference to conjugation in the base. This large di€erence between the dihydrodiazepine bases and their cations is interesting in that both species are made up inherently from the same six-electron push-pull system, but the symmetry and the possibility for delocalisation of charge in the cation, but not present in the base, obviously confer quite di€erent types of structure on the two species.Whereas the vinamidinium systems of the cations are inherently symmetrical, the vinamidine systems of the bases are not and can only achieve symmetry in solution by a very rapid 1,5-shift of a hydrogen atom between the 1- and 4-nitrogen atoms.In the crystal the 2,3-cylohexano-6-phenyldihydrodiaze- pine molecules are lined in chains through N(1) H N(4) hydrogen bonds between neighbouring molecules. In the 5,7-diphenyl analogue the NH is hydrogen bonded to the oxygen atom of a molecule of propan-2-ol of crystallisation and N(4) is hydrogen bonded to the HOCH(Me)2 group of the propan-z-ol. Technique used: X-Ray di€raction Tables 1 and 2: Bond lengths and bond angles for 3 and 4 Appendix: Crystal data for 3 and 4 Received, 17th July 1997; Accepted, 22nd October 1997 Paper E/7/05112C References cited in this synopsis 1 Part 29, D.Lloyd, H. McNab and S. Parsons, J. Chem. Res., 1998, preceding paper. 2 For a review see D. Lloyd and H. McNab, Adv. Heterocycl. Chem., 1993, 56, 1. 3 D. Lloyd and D. R. Marshall, Chem. Ind. (London), 1972, 335. 4 G. Schwarzenbach and K. LuE tz, Helv. Chim. Acta, 1940, 23, 1162; D.Lloyd, R. H. McDoughall and D. R. Marshall, J. Chem. Soc. (C), 1966, 780. 5 J. P. Declercq, G. Germain and M. Van Meersche, Acta Crystallogr., Sect. B, 1979, 35, 1175. 6 H. Zimmer, A. Amer, D. Ho and R. Palmer-Sungail, J. Heterocycl. Chem., 1991, 18, 1501. 7 D. Lloyd, K. S. Tucker and D. R. Marshall, J. Chem. Soc., Perkin Trans. 1, 1981, 726. 8 D. Lloyd, H. McNab and D. R. Marshall, Aust. J. Chem., 1977, 30, 365. 13 D. Lloyd, G. Ferguson and B. L. Ruhl, Acta Crystallogr., Sect. C, 1991, 47, 1290. 14 G. Ferguson, D. Lloyd, H. McNab, D. R. Marshall, B. L. Ruhl and T. Wieckowski, J. Chem. Soc., Perkin Trans. 2, 1991, 1663. 15 A. J. Blake, H. McNab, L. C. Monahan, S. Parsons and E. Stevenson, Acta Crystallogr., Sect. C, 1996, 52, 2814. Tab 3 Some comparative bond lengths Bond length D Compound N(1)�}C(7) C(7)�}C(6) C(6)�}C(5) C(5)�}N(4) 6-Phenyl-1(cation)1 1.315(4) 1.391(4) 1.405(4) 1.305(4) Cation from 31 1.318(4) 1.393(4) 1.388(4) 1.322(4) 3 (base) 1.335(3) 1.364(3) 1.451(3) 1.289(2) 5,7-Diphenyl-1 (cation)13 1.335(6)a 1.384(6) 1.406(6) 1.328(6)a 4 (base) 1.349(3) 1.360(3) 1.430(3) 1.294(3) aThese N(1)�}C(7) and C(5)�}N(4) bonds are longer than usual, see refs. 1 and 14. J. CHEM. RESEARCH

ISSN:0308-2342    

DOI:10.1039/a705112c

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Synthesis of 2,3-Dihydro-6-methylthieno[2,3-c]furan(Kahweofuran), a Coffee Aroma Component, from anAcyclic PrecursorElisabetta Brenna,a Claudio Fuganti,*a Stefano Serraa andAndrea DuliobaDipartimento di Chimica del Politecnico, Centro CNR per la Chimica delle Sostanze Organiche Naturali,ViaMancinelli 7,Milano I-20131, ItalybPerfetti s.p.a,Via XXVAprile, 7/9, Lainate (MI) I-20020, ItalyKahweofuran 1, one of the impact flavours of roasted coffee, was obtained from the acyclic unsaturated ester 8, produced in aStobbe condensation of -methylcinnamaldehyde with dimethyl succinate, through the key intermediate tetrahydrothiophene 14and the C-7 derivatives 20 or 24, respectively.2,3-Dihydro-6-methylthieno[2,3-c]furan 1 was characterisedthirty years ago1 as one of the impact avour componentsof roasted coee.However, a full evaluation of its aromaticsignicance is apparently still lacking because it is not easilysynthesised.Two approaches to the C-7 framework of 1 have beenreported.The rst one2 uses the commercially available4,5-dihydrothiophen-3(2H)-one (2) and involves a Claisencondensation with ethyl acetate and a Grignard reactionwith methoxymethylmagnesium chloride in order to preparethe key intermediate 3 from which 1 is obtained upon acidtreatment. The reported reactions lack specicity and thusdicult isomeric separations are required. Alternatively,6 1is accessible from 3,4-dibromofuran 4, from which the C-7derivative 5 is obtained through two C0C bond formingreactions based on carbanion chemistry.These know pro-cedures either aord low overall yields from expensive pre-cursors or require the extensive use of organometallicreagents at low temperature. Thus, a more direct access tokahweofuran 1 seemed desirable and here we report theresults of our studies.We selected substrate 8, obtained by a Stobbe conden-sation7 of a-methylcinnamaldehyde with dimethyl succinate,as a suitable starting material because it contains the entirecarbon framework (see brackets in structural formula 8) andall the functionalities required to obtain product 1, SchemeA.Indeed, reduction of the free carboxyl moiety of 8 tocarbinol 10, via NaBH4 reduction8 of the mixed anhydride9, followed by exchange of the oxygen and the sulfur func-tionality under Violante conditions,9 aorded compound 12.This latter underwent ring closure to tetrahydrothiophene14 quantitatively on treatment with NaOMe in methanol.The product 14 was most likely derived from an intra-molecular Michael addition of the intermediate sulfurnucleophile 13 onto the a,b-unsaturated ester moiety,10 andwas found to be a 2:1 mixture of two diastereoisomers onthe basis of NMR spectra.Tetrahydrothiophene 14 was quantitatively reduced withLiAlH4 in Et2O to 15, whose hydroxy group was protectedby conversion into the benzoate ester 16. Indeed, reactionwith ozonized oxygen at £¾78 8C in methylene chloride,followed by Ph3P treatment, transformed 16 into a mixtureof benzaldehyde and sulfoxide 17.This latter was reducedto the sulde 18 on reaction with PCl3 at £¾50 8C in DMF.Treatment of the ester 18 with catalytic NaOMe in metha-nol aorded carbinol 19. Finally, Swern oxidation11 of 19provided the 1,4-dicarbonyl compound 20 which cyclized tokahweofuran 1 upon treatment with boiling dilute sulfuricacid.12Alternatively, product 1 was obtained from 15 through asequence involving Swern oxidation to the aldehyde 21,whose carbonyl moiety was protected by conversion into theacetal 22.Ozonolysis, Ph3P treatment and PCl3 reductionof the intermediate sulfoxide 23 gave the ketoacetal 24,similarly providing kahweofuran 1 on acid treatment.Both these synthetic paths, using tetrahydrothiophenes20 and 24 as direct precursors of kahweofuran, arecharacterised by the common key intermediate 14, whosepreparation involved a troublesome Violante reaction onsubstrate 10. Two dierent solutions were devised.Theacetate ester 12 was obtained from 10 via the correspondingbromo derivative 11, accessible upon treatment withN-bromosuccinimide and Ph3P in methylene chloride,followed by displacement with potassium thiocetate indimethylformamide.The second alternative took advantage of lactone 25,which was obtained in quantitative yield by ring closure ofthe hydroxy ester 10 promoted by sodium methylate inmethanol, Scheme 3. Subsequent treatment of lactone 25with gaseous hydrogen bromide in methanol¡Ómethylenechloride solution aorded the bromo derivative 11 via anunusual acidic cleavage of the lactone ring.13In the synthetic sequences described all the reactionsinvolved are regiospecic and no expensive precursors ordangerous organometallic reagents are used.Moreover, thesedesigned synthetic paths can be considered as a generalmethod to prepare a wide variety of 2,3-disubstituted tetra-hydrothiophenes. These latter derivatives are suitable pre-cursors of bicylic systems showing a heterocyclic ringcondensed on the tetrahydrothiophene moiety.J.Chem. Research (S),1998, 74¡Ó75J. Chem. Research (M),1998, 0551¡Ó0563Scheme 3*To receive any correspondence.74 J. CHEM. RESEARCH (S), 1998Techniques used: 1H NMR, IR, GC-MS Schemes: 3 References: 13 Received, 28th August 1997; Accepted, 28th October 1997 Paper E/7/06334B References cited in this synopsis 1 M. Stoll, M. Winther, F. Gautschi, I. Flament and B. Willhalm, Helv. Chim.Acta, 1967, 50, 628. 2 G. Bu È chi, P. Degen, F. Gautschi and B. Willhalm, J. Org. Chem., 1971, 36, 199. 6 M. Gorzynski and D. Rewicki, Liebigs Ann. Chem., 1986, 625. 7 F. Fichter and S. Hirsch, Chem. Ber., 1901, 34, 2188. 8 K. Ishizumi, K. Koga and S-I. Yamada, Chem. Pharm. Bull., 1968, 16, 492. 9 R. P. Violante, Tetrahedron Lett., 1981, 22, 3119. 10 J. L. Szabo and E. T. Stiller, J. Am. Chem. Soc., 1948, 70, 3667. 11 K. Omura, A. K. Sharma and D. Swern, J. Org. Chem., 1976, 41, 957. 12 C. Botteghi, L. Lardicci and R. Menicagli, J. Org. Chem., 1973, 38, 2361. 13 D. S. Noyce and J. H. Can®eld, J. Am. Chem. Soc., 1954, 76, 3630. OR OMe Ph O O C7 EtOCOCl, Et3N THF 8 R = H 9 R = CO2Et Ph OMe O X NaBH4, water NBS, PPh3, CH2Cl2 10 X = OH 11 X = Br KSCOMe, DMF 12 X = SCOMe 13 X = S MeCOSH, THF Ph R S Ph S Ph S O OMe OR i, (CF3CO)2O, DMSO ii, Et3N LiAlH4, THF CH(OMe)3, TSOH, MeOH 21 R = CHO 22 R = CH(OMe)2 15 R = H 16 R = COPh 14 O CH(OMe)2 S+ O S+ OCOPh O– O– i, O3, CH2Cl2–MeOH ii, PPh3 i, O3, CH2Cl2–MeOH ii, PPh3 23 17 O CH(OMe)2 S O R S PCl3, dry DMF 24 PCl3, dry DMF 18 R = CH2OCOPh 19 R = CH2OH 20 R = CHO MeONa, MeOH i, (CF3CO)2O, DMSO, CH2Cl2 ii, Et3N, CH2Cl2 1 H2SO4 0.1 N H2SO4 0.1 N MeONa, MeOH PriOCON NCO2Pri, Ph3P, Scheme A J. CHEM. RESEARCH (S), 1998 75

ISSN:0308-2342    

DOI:10.1039/a706334b

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Synthesis and Pyrolytic Behaviour of Chiral Thiazolidine1,1-DioxidesR. Alan Aitken* and Shaun T. E. MesherSchool of Chemistry, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, UKFive chiral thiazolidine 1,1-dioxides have been prepared and the pyrolytic behaviour of this class of compound has been examinedfor the first time.In recent papers we have described the synthesis of chiral4,5-dihydrothiazole 1,1-dioxides1 and thiazolidin-2-one 1,1-dioxides2 and their thermal behaviour upon ash vacuumpyrolysis (FVP).In a continuation of this study, it was ofinterest to examine the thermal decomposition of thethiazolidine 1,1-dioxides 1 which might be expected to pro-duce chiral azetidines 2. If this were successful, introductionof additional functionality by alkylation a- to the SO2 groupprior to pyrolysis could be envisaged, leading to versatilesynthetic building blocks. We describe here the preparationof ve thiazolidine 1,1-dioxides and their behaviour uponFVP.NSO2R2 R3 R4R11NR4 R3R2R12We rst considered preparing the required thiazolidinesby reduction of the corresponding 4,5-dihydrothiazoles 3which are readily available in enantiomerically pure form ina few steps from amino acids.1 Use of Meyers' aluminiumamalgam method,3 which is eective for 4-unsubstitutedthiazolidines, did produce the thiazolidine 4 in good yieldbut only for the 2-tert-butyl example 3c.When this methodwas applied to the 2-phenyl compounds 3a,b it resulted inreductive dimerisation to give the 2,2'-bi(thiazolidines) 5 ingood to excellent yield.As far as we are aware, such reduc-tive coupling of 4,5-dihydrothiazoles has not been observedbefore, although the corresponding reaction of 2-aryl-4,5-dihydrooxazolium salts using Zn¡ÓTMSCl or electrochemicalreduction has been reported recently.4 The stereochemistryof these reductions is of some interest. The thiazolidine 4was obtained as a 75:25 mixture of diastereomers indicatinga rather poor degree of stereocontrol at the newly formedcentre.The situation with 5 is rather more complex sincetwo new stereogenic centres are formed in addition to thetwo derived from 3. Consideration of the symmetry ofthe four possible diastereomers of 5 gives a theoreticalmaximum of 36 13C NMR signals for 5a and 48 for 5b.Although the complexity of the spectra in the aromatic CHregion precluded full assignment, the appearance of sets offour approximately equal signals in each of the otherregions including that for the atoms at the newly formedstereogenic centres (dC 90¡Ó95 ppm) clearly showed thecoupling to have taken place without selectivity to give analmost equal mixture of all four possible diastereomers.To obtain some further thiazolidines, we made use of thewell known reaction of cysteine with aldehydes to obtainfour examples of thiazolidines 6 and then converted theseinto the methyl esters 7.In the cases 7c¡Óe where R16H,these were obtained as approximately 2:1 mixtures ofdiastereomers at the newly formed stereocentre (Table 1).We have previously reviewed the oxidation of ve-membered rings containing N and S,7 and noted that almostall successful S-oxidations of thiazolidines have been onN-substituted examples while, in the absence of an N-substituent, ring-opened products are generally formed.The thiazolidines 4 and 7 were therefore N-acetylated usingacetic anhydride to aord 8a¡Óe. For oxidation to theHNSCO2HR16HNSCO2MeR17SOCl2MeOH6,7 R1bcdeHEtPriPhHNSR2 R3R14 or 7NSR2 R3 AcR18NSO2R2 R3 AcR19Ac2O [O]1,1-dioxides 9 the use of potassium permanganate andbenzoic acid under phase-transfer conditions1 generally gaveexcellent results (Table 1).The sulfones 9 were all obtainedas crystalline solids. In the case of 9c,d the diastereomerratio was preserved from 7 while signicant enrichmentoccurred at the stage of the acetylation in the cases of 7a,eto give 9a in particular as essentially a single diastereomer.This phenomenon, which involves epimerisation at C-2 bymeans of a ring-opened intermediate, has been describedin detail before by Gyo rgydea k and co-workers.8 The 33SNMR spectrum of 9d was readily obtained at naturalabundance and showed a relatively sharp signal at dS 18.7(w1/2 400 Hz) which is in the expected range for cyclicsulfones, although this is the rst thiazolidine 1,1-dioxide tobe observed.For both 8a and 9a, the NMR spectra werecomplex at room temperature owing to restricted rotationabout the N-acetyl group and this was quantied by meansof a variable temperature study of both the 1H and 13CNMR spectra over the range £¾40 to +50 8C.Calculationsbased on the observed coalescence temperatures for severalsignals for each compound gave average energy barriers torotation of DG% 61.7 kJ mol£¾1 for 8a and 60.9 kJ mol£¾1 for9a and dierences in energy between the two forms of DG0.79 kJ mol£¾1 for 8a and 0.39 kJ mol£¾1 for 9a.Although thermal extrusion of SO2 from a wide varietyof cyclic sulfones has been examined,10 no example of aJ.Chem. Research (S),1998, 76¡Ó77J. Chem. Research (M),1998, 0564¡Ó0579*To receive any correspondence (e-mail: raa@st-and.ac.uk).76 J. CHEM. RESEARCH (S), 1998thiazolidine 1,1-dioxide has apparently been studied before. The compounds 9a±e were found to react under FVP conditions in the range 600±700 8C and the results are sum- marised in Table 3. For 9a the major product was allyl- benzene, indicating that loss of SO2 has been accompanied by complete fragmentation of the ring.As shown in Scheme 2, this produces the diradical 10 which apparently fragments to give trimethylacetonitrile and, perhaps by hydrolysis of the corresponding imine upon isolation, trimethylacetalde- hyde. No non-gaseous product derived from the N-acetyl group was isolated. The formation of 1-phenylpropyne 11 presumably involves a secondary dehydrogenation of the allylbenzene in an excited state, since the latter was re- covered unchanged upon repyrolysis at the same tempera- ture.The unexpected formation of 2-tert-butylthiazole 12 together with bibenzyl most likely results from loss of benzyl radical from 9a followed by aromatisation with loss of the elements of acetaldehyde. For 9b±e methyl acrylate was produced in each case together with methanol and acetic acid. Only for 9e were benzonitrile and benzaldehyde produced, corresponding to the fragmentation of the diradical corresponding to 10 for 9a.For 9b and e only, acetamide was also obtained. We have thus established that, although chiral thiazol- idine 1,1-dioxides can be prepared in good yield, the conditions required to bring about extrusion of SO2 are such that only alkenes and other products resulting from complete fragmentation of the ring are obtained. Techniques used: 1H, 13C and 33S NMR, IR, MS, GC±MS, �ash vacuum pyrolysis References: 16 Tables: 3 (yields, 13C NMR data and pyrolysis products for thiazol- idine dioxides) Received, 29th October 1997; Accepted, 31st October 1997 Paper E/7/07788B References cited in this synopsis 1 R. A.Aitken, D. P. Armstrong, R. H. B. Galt and S. T. E. Mesher, J. Chem. Soc. Perkin Trans. 1, 1997, 935. 2 R. A. Aitken, D. Armstrong, R. H. B. Galt and S. T. E. Mesher, J. Chem. Soc. Perkin Trans. 1, 1997, 2139. 3 A. I. Meyers and J. L. Durandetta, J. Org. Chem., 1975, 40, 2021. 4 T. Shono, N. Kise, R. Nomura and A. Yamanami, Tetrahedron Lett., 1993, 34, 3577. 7 R. A. Aitken, D. P. Armstrong and S. T. E. Mesher, Prog. Heterocycl. Chem., 1990, 2, 1. 8 L. Szila gyi and Z. GyoÈ rgydea k, J. Am. Chem. Soc., 1979, 101, 427; Z. GyoÈ rgydea k, M. Kajta k-Peredy, J. Kajta r and M. Kajta r, Liebigs Ann. Chem., 1987, 927. 10 R. A. Aitken, I. Gosney and J. I. G. Cadogan, Prog. Heterocycl. Chem., 1992, 4, 1; 1993, 5, 1. Table 3 Products from FVPof thiazolidine1,1-dioxides 9 (%) T/ 8C R2R3C=CH2 R1CN R1CHO AcOH AcNH2 MeOH a 600 43 9 7 ^ ^ ^a b 700 22 ^ ^ 11 11 11 c 600 17 ^ ^ 47 ^ 33 d 700 28 ^ ^ 60 0.5 30 e 700 47 18 17 73 ^ 41 aAdditional products: 11 (5%), 12 (6%), PhCH2CH2Ph (7%). N S O2 CH2Ph Ac But 9a N S But 12 + PhCH2CPh FVP 600 °C –SO2 CH2Ph But N• Ac • + PhC CMe 10 ButCN ButCHO + 11 Scheme 2 Table 1 Formation of thiazolidine1,1-dioxides 9 4 or7 8 9 R1 R2 R3 % Yield from 3 or 6 d.r. % Yield from 4 or 7 d.r. % Yield from8 d.r. a But CH2Ph H 80 75:25 81 96:4 90 >99:1 b H H CO2 Me 79 ^ 96 ^ 50 ^ c Et H CO2Me 58 67:33 89 63:37 90 66:34 d Pri H CO2 Me 66 69:31 97 64:36 95 59:41 e Ph H CO2Me 39 62:38 *98 88:12 95 85:15 J. CHEM. RESEARCH (S), 1998 77

ISSN:0308-2342    

DOI:10.1039/a707788b

出版商:RSC    

年代:1998

数据来源: RSC

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C2-Symmetric Ligands for Asymmetric Catalysis basedon Feist's AcidAbdullah M. Al-Majid, Brian L. Booth* and Jonnes T. GomesDepartmentofChemistry, UMIST, P.O. Box 88,ManchesterM601QD,UKWe describe a study of some of the chemistry of Feist's acid and attempts to prepare new diol and diamine ligands as well as abis(indene) derivative.There have been several reports on the resolution of Feist'sacid. The earliest of these was by von Doering and Roth4using L-(£¾)-quinine as the resolving agent, while a recentpatent5 uses (R)-(+)-a-methylbenzylamine. As resolution isa critical issue if Feist's acid is to be a useful precursorto asymmetric ligands we carried out an investigation tocompare the two dierent methods.In our hands reactionbetween (2)-Feist's acid and L-(£¾)-quinine in reuxingethanol over 20 min gave a 43% yield of the L-quinine saltof (2R,3R)-(+)-1-methylidenecyclopropane-2,3-dicarboxylicacid {mp 183¡Ó184 8C, [a]23546£¾145 8 {c 0.4, EtOH} [lit.,9 mp146¡Ó147 8C, [a]23546£¾139.7 8 (c 0.7, EtOH)]} after fractionalcrystallisation from dry ethanol.Clearly, the mp of our saltwas at variance with that reported by von Doering,although the specic rotation values were in agreementwithin experimental error. Hydrolysis of the salt with 10%sulfuric acid gave (2R,3R)-(+)-Feist's acid, (+)-1 {mp207 8C, [a]23546+116 8 (c 0.4, EtOH) [lit.,4 mp 203¡Ó205 8C,[a]23546+176 8 (c 0.7, EtOH)]} in 84% yield. This suggestedthat either our sample was impure, despite the agreement inthe mps, or that the quoted specic rotation values were in-accurate.In an eort to resolve this issue the reaction between (2)-Feist's acid and 1 mol equivalent of (R)-(+)-a-methylbenzyl-amine was carried out in aqueous isopropyl alcohol to givea mixture of diastereomeric salts in 89% yield.Fractionalcrystallisation from isopropyl alcohol¡Ówater (3:1) gave thepure (+)-a-methylbenzylammonium salt of (2R,3R)-(+)-1-methylidenecyclopropane-2,3-dicarboxylic acid (+)-2 in73% of the theoretical yield; the mp and specic rotationvalues agreed well with those reported5 Hydrolysis of thissalt using 1 M HCl in ethyl acetate gave (2R,3R)-(+)-Feist'sacid in 92% yield (mp 204¡Ó205 8C, [a]23546+155.5 8 (c 0.70,EtOH}).Hydrolysis of the mother liquor gave impure(2S,3S)-(£¾)-Feist's acid {mp 199.2¡Ó199.7 8C, [a]23546£¾95.3 8(c 0.81, EtOH)}. This last method of resolution is more con-venient practically and gives superior yields to the previousmethod described by von Doering.Our results indicatethat the specic rotation value for the pure enantiomers issomewhat lower than that reported. As a further indicationof purity, a sample of (+)-1 prepared by the last methodwas esteried to give the known dimethyl ester (R,R)-3 asa single enantiomer {mp 33¡Ó34 8C, [a]23D+123.3 8 (c 0.76,CCl4) [lit.,5 mp 32¡Ó33 8C, [a]23D+124.8 8 (c 0.76, CCl4)]} in89% yield. The optically pure ester could also be obtaineddirectly from the salt (+)-2 in 71% yield under rather moreforcing conditions (see Scheme 2).Furuta et al.6 have previously described a procedure forthe synthesis of (+)-(1S,2S)-cyclopropane-1,2-dicarboxylicacid by the condensation of (£¾)-dimenthyl succinate dianionwith bromochloromethane followed by alkaline hydrolysisof the dimenthyl ester.This suggested a new alternativemethod of resolution for Feist's acid via the dimenthylesters. Consequently, treatment of (+)-Feist's acid withtwo equivalents of L-(£¾)-menthol in reuxing toluene for48 h gave the expected mixture of diastereomers in 73%yield.Repeated separation by column chromatographyfollowed by recrystallization from dry methanol gave pure(£¾)-dimenthyl (2R,3R)-(£¾)-1-methylidenecyclopropane-2,3-dicarboxylate 4 {[a]23D£¾122 8 (c 0.47, CHCl3)} in 59% of thetheoretical yield (Scheme 2). Attempts to hydrolyse the die-ster using the procedure applied successfully by Furuta etal.3 (10% KOH solution in 9:1 methanol¡Ówater at 60 8C for4 h) resulted in total racemization in our hands.VariousJ. Chem. Research (S),1998, 78¡Ó79J. Chem. Research (M),1998, 0580¡Ó0589HO2CHO2C(¡Ó)-1PhMe NH3+ ¡VO2CHO2CHO2CHO2Ci(+)-2 (+)-1iiv iiiMeO2CMeO2C(+)-3HOPh2CHOPh2C(¡V)-5(¡V)-Menthyl-O2C(¡V)-Menthyl-O2C(¡V)-4vi viiv(¡V)-8OPh PhOTiClClPh PhHOH2CHOH2C10xiii viiMesOCH2MesOCH2(¡V)-11NNN N3N3 N3rac-13viiiN3CH2N3CH2rac-12H2NCH2H2NCH2rac-9xirac-14ixR3 R3HOHOR3 R3R1R26 R3 = Ar7 R1 = R2 = R3 = MexiixScheme 2 Reagents and conditions: (i) (R)-()-PhCHMeNH2,PriOH^H2O (9:1), 80 8C; ii,1MHCl, EtOAc; iii, MeOH, conc.H2SO4(cat), 35 8C, 24 h; iv,MeOH, conc. H2SO4 (cat), 35 8C, 48 h;v, L-(£¾)-menthol, p-TsOH (cat.), toluene, reflux, 48 h; vi, (a) PhMgBr,THF, reflux, 2.5h; (b) NH4Cl; vii, LiAlH4,THF,£¾78 8C to roomtemp.,24 h; viii,MeSO2Cl, CH2Cl2, Et3N, 0 8C, 2 h; ix, NaN3, DMF, 60 8C, 6 h;x, NaN3, DMF,100 8C,10 h; xi, 5% Pd^CaCO3, EtOH, H2, roomtemp.,24 h; xii, indeneMgBr,THF, reflux, 30min, xiii, (a) BuLi, Et2O, 0 8C;(b) TiCl4, CH2Cl2 roomtemp *To receive any correspondence.78 J. CHEM.RESEARCH (S), 1998attempts at hydrolysis under acidic conditions [CF3CO2H, CH2Cl2 at 0 8C, Me3SiCl, NaI in CH3CN] were equally unsuccessful. The optically pure dimethyl ester (R,R)-3 reacted with 2 mol equiv. of phenylmagnesium bromide in THF to give a single enantiomer of the diol (2R,3R)-(¡)-5 {[a]23 D¡276 8 (c 0.25, CCl4)} in 58% isolated yield (Scheme 2). The same compound could also be obtained directly from the dimenthyl ester 4 under similar conditions, but the yield was poor (10%), presumably owing to steric hindrance from the menthyl chiral auxiliary.Diol 5 has a super®cial similarity to the tetraaryldioxolanedimethanol (TADDOL, 6) and hexamethyldioxolanemethanol (HMDDOL, 7) ligands, which, as their titanium derivatives, have been used success- fully by Seebach and others for asymmetric alkylation9 and allylation10 of aldehydes and for Diels±Alder reactions.11±13 Work is currently in progress to assess the e�ciency of the titanium complexes of diol 5 in similar reactions.Preliminary results indicate that the titanium complex 8 has activity for the addition of dialkylzinc to aldehydes, but as yet the yields and ee values have not been optimised. The diamine 9 has not been described previously and an initial attempt at synthesis was by conversion of (R,R)-3 to the known (R,R)-diol 1017 followed by treatment under Mitsonobu conditions with diphenylphosphoryl azide. Although all of the starting material was consumed, this reaction was not clean and the desired diazide could not easily be separated from the impurities. More success was achieved using the classical conversion of 10 into its dimesylate 11 followed by reaction with sodium azide in DMF at 60 8C for 6 h to give the diazide 12 in 84% isolated yield.The conditions of this reaction are critical and if a higher temperature (100 8C) is emplyed then the spirotriazo- line 13 is the major product, formed by the 1,3-dipolar addition of 12 to the C=C bond of a second molecule.Hydrogenation of 12 gave the desired diamine 9 in 60% yield (Scheme 2). The diamine is an oil, which is di�cult to purify as it is very sensitive to oxidation. The rac-dimesylate 11 proved to be a useful precursor to the C2-symmetric bis(indene) derivative rac-14 formed in 69% yield by reaction with 2 mol equiv. of indenyl- magnesium bromide.Work is in progress to synthesise ansa- titanium and -zirconium complexes of this ligand and its separate enantiomers to explore their e�ciency as catalysts for asymmetric alkylation, hydrogenation and Ziegler±Natta polymerization of a-ole®ns. Thanks are due to the Conselho Nacional de Desenvolvimento Cienti®co e Tecnolo gico, Brazil, for ®nancial support (to J. T. G.). Techniques used: 1H and 13C NMR References: 17 Schemes: 2 Received, 26th August 1997; Accepted, 3rd November 1997 P/7/06185D References cited in this synopsis 4 W. von Doering and H. D. Roth, Tetrahedron, 1970, 26, 2825. 5 J. D. Godfrey, R. H. Mueller, R. T. P. Kissick and J. Singh, US Pat. 5185463, 1993. 6 K. Furuta, K. Iwanaga and H. Yamamoto, Org. Synth., 1989, 67, 76. 9 B. Weidmann and A. Hafner, Chem. Rev., 1992, 92, 807. 10 H. Takahashi, A. Kawabata, H. Niwa and K. Higashiyama, Chem. Pharm. Bull., 1988, 35, 803; 1987, 1604. 11 K. Narasaka, N. Iwasawa, M. Inoue, T. Yamada, M. Nakashima and J. Sugimori, J. Am. Chem. Soc., 1989, 111, 5340. 12 G. H. Posner, J.-C. Carry, J. K. Lee, D. S. Bull and H. Dai, Tetrahedron Lett., 1994, 35, 1321. 13 E. J. Corey and Y. Matsumura, Tetrahedron Lett., 1991, 32, 6289. 17 C.-N. Hsiao and S. M. Hannick, Tetrahedron Lett., 1990, 31, 6609. J. CHEM. RESEARCH (S), 1998 79

ISSN:0308-2342    

DOI:10.1039/a706185d

出版商:RSC    

年代:1998

数据来源: RSC

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Synthesis of -Corocalene{ Koon-Sin Ngo, Kung-Kai Cheung and Geoffrey D. Brown* Chemistry Department, The University of Hong Kong, Pokfulam Rd., Hong Kong -Corocalene, a constituent of hop oil, has been synthesized in four steps fromthemonoterpene (+)-pulegone. The sesquiterpene a-corocalene (1) was Rrst isolated as a constituent of hop oil by Japanese workers in 19691 and has been subsequently reported in essential oils and Juniper2 and members of the Lauraceae family.3 No synthesis of this compound has been reported following its isolation as a natural product, although preparations of the isomeric ses- quiterpene hydrocarbons g-calacorene and a-calacorene have appeared.4,5 The completely aromatized naphthalene system of cadalene (with one extra degree of unsaturation as com- pared to a-corocalene) has also been obtained by synthesis.6 A common synthetic strategy in the synthesis of sesquiter- penes is to perform Robinson annulation of commercially available menthane monoterpenes.7,8 It has been reported that the pyrrolidene enamine of (+)-pulegone (2) undergoes such a reaction,9 but we were unable to form the enamine of 2 despite repeated attempts. Pulegone a-epoxide (3a), however, did readily form the desired enamine 4 in good yield (Scheme 1).Interestingly, the b-epoxide (3b), which was normally present in combination with the a-epoxide (MCPBA epoxida- tion of pulegone showed no diastereoselectivity), completely failed to react with pyrrolidine even under the most forcing conditions.Compounds 3a and 3b were separated by HPLC. X-Ray crystallographic analysis (Fig. 1)% showed that the C-1 methyl group and the new epoxide functionality were trans to one another in 3b and cis in 3a. Since the absolute stereo- chemistry at C-1 is known for (+)-pulegone starting material and this chiral centre is not expected to undergo alteration during the course of epoxidation, the absolute stereo- chemistry for 3a and 3b can be determined as shown.The enamine 4 underwent smooth Robinson annulation with methyl vinyl ketone (MVK), as expected, to give the bicyclic unsaturated ketone 5a. It was later discovered that 5a could be made directly by Robinson annulation of the 3a�}3b epoxide mixture with MVK in the presence of base. As previously, the b-epoxide (3b) was completely unreactive. Direct Robinson annulation also resulted in production of small amounts of the 1b-epimer (5b) and uncyclized product 6.The two epimers 5a and 5b were very clearly distinguished from their 13C NMR spectra (see Table 1) which showed a pronounced upReld shift (ca. 5 ppm) in the 14-methyl group of 5b as a result of gauche e€ects when this substituent is forced to adopt an axial conformation. NOESY spectra for 5b also demonstrated strong axial�}axial correlations from 14-H to 8a-H and 2a-H, which were absent from compound 5a. The appearance of diastereoisomers at this step in the synthesis was considered unimportant as this new chiral centre would be eliminated in the Rnal product.Introduction of the Rnal carbon atom required in the structure of 1 was achieved by Grignard reaction to yield the unstable alcohol 7. Treatment of 7 with mild acid resulted in dehydration at both the tertiary hydroxide and epoxide groups accompanied by double bond migration to yield the aromatic B ring of a-corocalene. In fact, this reaction is so facile that it can be a€ected by the acidic impurities in CDCl3: thus, simply allowing a solution of 7 in an NMR tube to stand overnight resulted in conversion into 1.Low-Reld 1H NMR data reported for the natural product a-corocalene1 agreed with that for 1 obtained through syn- thesis. Complete 13C and 1H NMR assignments for 1 and for all of the intermediates in the synthesis (Table 1) were rigorously determined by means of the 2D-NMR techniques HSQC (which shows 13C connected to 1H by a single bond) and HMBC (2- and 3-bond couplings between 13C and 1H). 1H�}1H COSY spectra were normally used to conRrm these assignments and NOESY and 1H�}1H J-resolve experiments were used to determine the relative stereochemistries. Experimental Chemical shifts are expressed in ppm (d) relative to Me4Si as in- ternal standard. All NMR experiments were run on a Bruker DRX 500 instrument. Two-dimensional spectra were recorded with 1024 data points in F2 and 256 data points in F1. Mass spectra were J.Chem. Research (S), 1998, 80�}81$ O O O O O H MCPBA O O H MVK + O 2 3a a-epoxide 3b b-epoxide 5a a-H 5b b-H 6 O H 7 N O 4 C4HgN OH MVK 1 15 4 1 14 10 7 12 11 13 H+ MeMgl Scheme1 Synthetic route to a-corocalene from(+)-pulegone Fig. 1 ORTEP diagrams for 3a and 3b $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). %Full crystallographic details, excluding structure factors, have been deposited at the Cambridge Crystallographic Data Centre (CCDC).See Instructions for Authors, J. Chem. Research (S), 1998, Issue 1. Any request to the CCDC for this material should quote the full literature citation and the reference number 423/6. *To receive any correspondence (e-mail: gdbrown@hkucc.hku.hk). 80 J. CHEM. RESEARCH (S), 1998recorded in the EI mode at 70 eV on a Finnigan-MAT 95 MSspectrometer. IR spectra were recorded in solution on a ShimadzuFTIR-8201 PC-7 spectrometer.TLC plates were developed usingp-anisaldehyde. Column chromatography was performed using silicagel 60¡Ó200 mm (Merck). HPLC separations were performed using aPREP-SIL 20 mm25 cm column, ow-rate 8 ml min£¾1.Epoxidation of Pulegone (2).m-Chloroperbenzoic acid(MCPBA) (15.96 g) was added to pulegone (2) in CH2Cl2 (7.61 g,130 ml) and the mixture was cooled in an ice bath. The mixture wasstirred for 1 h (a white precipitate appeared after 15 min), thenwashed with Na2SO3 (10%; 2100 ml) and NaHCO3 (2100 ml).The combined aqueous washings were back-extracted with CH2Cl2(250 ml) and combined organic layers, dried (MgSO4) and thesolvent removed under reduced pressure to yield 3a/3b in a 1:1 ratio(8.38 g, 99.8%). The two isomers were separated by HPLC in 25%(v/v) EtOAc¡Óhexane [Rt (3a) 13.6 min; Rt (3b) 14.6 min].Pulegone-epoxide (3a): crystals, mp <40 8C; []D £¾ 17.38 (c 3.5, CHCl3);m/z (intensity %): 168.1146 (M+, =0.4 mmu for C10H16O2)(35), 153 (100), 126 (10), 125 (11); max/cm£¾1 3015, 2964, 2932,1720; H (CDCl3) 2.43 (3 H, br m), 2.21 (1 H, ddd, J 15.3, 12.3, 4.3Hz), 1.98 (1 H, m), 1.44 (3 H, s), 1.23 (3 H, s), 1.06 (3 H, d, J 7.1Hz); C (CDCl3) 207.6 (C), 70.2 (C), 63.5 (C), 49.5 (CH2), 30.7(CH), 30.2 (CH2), 26.3 (CH2), 20.0 (CH3), 19.6 (CH3), 18.9 (CH3).Pulegone -epoxide (3b): crystals mp <40 8C; []D 26.08 (c 3.1,CHCl3).m/z (intensity %) 168 (28) 153.0925 (100) (M+£¾CH3,=£¾ 1.0 mmu for C9H13O2), 126 (10), 111 (5); max/cm£¾1 (CHCl3)3015, 2963, 2930, 1720; H (CDCl3) 2.50 (1 H, dt, J 12.8, 2.8 Hz),1.44 (3 H, s), 1.22 (3 H, s), 1.08 (3 H, d, J 6.1 Hz).C (CDCl3)206.5 (C), 70.3 (C), 63.3 (C), 51.4 (CH2), 34.0 (CH), 33.0 (CH2),30.0 (CH2), 22.1 (CH3), 19.8 (CH3), 19.4 (CH3).Reaction of Pyrrolidine with Pulegone Epoxide (3a/3b).Pyrroli-dine (1.07 g), pulegone epoxide (3a/3b) (0.465 g) and benzene (5 ml;sodium-dried) were mixed together and allowed to stand over mol-ecular sieve (3 g; 4 A ).The reaction was monitored by TLC; after 5days, molecular sieve was removed and washed with benzene (25ml) and the combined organic fractions evaporated under reducedpressure to give a crude product (139 mg). 1H NMR showed this toconsist of the enamine of pulegone -epoxide (4) and unreactedpulegone -epoxide (3b). No unreacted pulegone -epoxide could bedetected. Compound 4: dark brown oil (isolated as a mixture with3b); H (CDCl3) 4.48 (1 H, d, J 2.2 Hz), 3.17 (2 H, dt, J 15.5, 6.9Hz), 1.35 (3 H, s), 1.33 (3 H, s), 1.03 (3 H, d, J 7.1 Hz); C (CDCl3)145.1 (C), 107.9 (CH), 66.6 (C), 62.2 (C), 49.4 (CH22), 30.0(CH2), 28.0 (CH2), 26.0 (CH2), 24.4 (CH22), 22.8 (CH3), 21.2(CH3), 19.7 (CH3).Robinson Annulation of Pulegone Epoxide (3a/3b) with MethylVinyl Ketone.To a mixture of pulegone epoxi (1.68 g),methanol (20 ml, anhydrous) and methyl vinyl ketone (0.73 g) wasadded potassium hydroxide (0.1 g).The mixture was stirred for 1 hat 50¡Ó60 8C and reuxed for a further 3 h. Solvent was removed bydistillation at reduced pressure, and the residue was taken up intoCHCl3. The organic layer was washed and dried and the solventwas removed to yield a product consisting predominantly ofunreacted -pulegone epoxide (3b) and the annulation product 5a,together with a little of the 1-epimer 5b and cyclohexanedione 6.Compound 5a was puried by column chromatography in 30%(v/v) EtOAc¡Óhexane (398 mg, 36% yield from 3a): oil; []D+95.08(c 0.65, CHCl3); m/z (intensity %) 192.1513 (M+£¾CO, =0.1mmu for C13H20O) (100), 177 (62), 164 (62), 150 (37), 122 (18);max/cm£¾1 (CHCl3) 2995, 2961, 2924, 2860, 1668; H (CDCl3) 5.83(1 H, d, J 1.3 Hz), 2.46 (1 H, ddd, J 17.0, 8.6, 8.6 Hz), 2.33 (1 H,ddd, J 17.0, 7.9, 4.8 Hz), 2.28 (1 H, ddd, J 11.2, 6.0, 6.0 Hz), 1.42(3 H, s), 1.31 (3 H, s), 1.05 (3 H, d, J 6.3 Hz).Compound 5b: oil;[]D+5.78 (c 5.5, CHCl3); max/cm£¾1 (CHCl3 3013, 2964, 2936,1670; H (CDCl3) 6.08 (1 H, d, J 2.4 Hz), 1.45 (3 H, s), 1.19 (3 H,s), 1.02 (3 H, d, J 7.1 Hz).Compound 6: H(CDCl3) 2.12 (3 H, s),1.42 (3 H, s), 1.17 (3 H, s), 1.14 (3 H, d, J 6.4 Hz).Grignard Reaction of 5a and Conversion into 1.A methylGrignard reagent (Mg 0.56 g; CH3I, 3.6 g; Et2O, 30 ml) was pre-pared by standard procedures. A solution of 5a (0.37 g) in Et2O (25ml) was added to the Grignard reagent and the mixture was stirredat room temperature for 1.5 h, and then worked up by standardprocedures. Following washing, drying and concentration of the or-ganic phase, compound 7 (180 mg) was isolated without need forfurther purication: colourless oil, H (CDCl3) 1.52 (3 H, s), 1.43 (3H, s), 1.14 (3 H, s), 0.96 (3 H, d, J 6.9 Hz).On standing overnightin CDCl3, compound 7 was converted into -corocalene 1; m/z(intensity %) 200.1567 (M+, =£¾ 0.2 for C15H20) (100), 185 (65),157 (13); max/cm£¾1 (CHCl3) 3013, 2967, 2924, 2870, 1601, 1475,1452; H (CDCl3) 7.01 (1 H, d, J 8.0 Hz), 6.94 (1 H, d, J 8.0 Hz),6.51 (1 H, d, J 1.4 Hz), 3.24 (1 H, septet, J 7.0 Hz), 2.73 (2 H, t,J 8 Hz), 2.24 (3 H, s), 2.19 (2 H, m), 1.95 (3 H, d, J 0.9 Hz), 1.21(6 H, d, J 7.0 Hz).We thank the CRCG for funding this research and theUniversity of Hong Kong for providing a postgraduatestudentship (to Mr Ngo).Received, 15th July 1997; Accepted, 7th October 1997Paper E/7/05069KReferences1 Y.Naya and M. Kotake, Bull. Chem. Soc.Jpn., 1969, 42, 2088.2 G. Vernin, C. Boniface, J. Metzger, C. Ghiglione, A. Hammoud,K.-N. Suon, D. Fraisse and C. Parkanyi, Phytochemistry, 1988,27, 1061.3 N. Hayashi, K. Yokochyo and H. Komae, Z. Naturforsch., TielC: Biosci., 1975, 30, 421.4 K. Adachi and M. Mori, Bull. Chem. Soc. Jpn., 1983, 56, 651.5 A. Heymes, M. Plattier and P. Teisseire, Recherches, 1974, 19,214.6 B. A. Nagasampagi, S. Dev, C. Rai and K. L. Murthy,Tetrahedron, 1966, 22, 1949.7 T.-L. Ho, Carbocyclic Construction in Terpene Synthesis, VCH,Weinheim, 1988, pp. 3¡Ó46.8 T.-L. Ho, Enantioselective Synthesis: Natural Products fromChiral Terpenes, Wiley, New York, 1992, p. 99.9 J. Elguero and B. Shimizu, Anal. Quim., 1988, 84, 198.Table 1 NMR data for 1, 5a, 5b, 6dC dHAtom 1 5a 5b 6 1 5a 5b 61 132.7 42.7 41.6 57.5 2.28 2.55 1.972a 24.9 25.3 25.3 19.87 2.73 1.81 1.95 1.862b 2.73 2.13 2.15 1.823a 28.1 35.8 36.2 40.9 2.19 2.33 2.30 2.583b 2.19 2.46 2.50 2.434 137.8 199.3 199.4 208.75 119.0 123.9 125.3 29.8 6.51 5.83 6.08 2.126 132.0 165.0 162.0 207.87 140.5 68.2 67.8 70.78a 122.3 29.4 25.7 30.1 7.01 1.91 2.05 2.018b 1.76 1.70 1.909a 128.0 31.1 31.8 33.0 6.94 1.53 1.80 1.569b 1.92 1.80 2.0010 131.6 35.0 34.6 38.1 1.62 2.28 1.7311 28.2 65.2 64.7 62.7 3.2412 23.6 20.4 19.7 19.93 1.21 1.31 1.19 1.1713 23.6 21.7 20.4 19.2 1.21 1.42 1.45 1.4214 19.6 19.5 14.7 20.3 2.24 1.05 1.02 1.1415 24.1 1.95J. CHEM. RESEARCH (S), 1998 81

ISSN:0308-2342    

DOI:10.1039/a705069k

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Stereoisomeric Styryl-substituted Pyrrolidines, 3,7-Diazobicyclo[3.3.0]octanes and 2-Styrylpyrroles fromCinnamaldehyde Iminium-N-methanide 1,3-Dipoles{Richard N. Butler* and Derval M. FarrellChemistry Department, University College Galway, IrelandThe reaction of cinnamaldehyde N-aryliminium methanide 1,3-dipoles with dimethyl maleate, dimethyl fumarate and some N-aryl-maleimides gives equalmixtures of stereoisomeric substituted pyrrolidines and a route to 2-styrylpyrroles with dimethyl acetylene-dicarboxylate.Azomethine methanide (ylide) 1,3-dipoles have proved to beimportant synthons for the pyrrole system.1¡Ó3 Routes tothese dipoles include thermal ring-opening of aziridines,1¡Ó4reactions of a-amino esters with carbonyl compounds,5¡Ó6reactions of amines with aldehydes7 and desilylation of tri-methylsilylmethyliminium salts.8,9 We have recently exam-ined10 the stereochemistry of the cycloadducts of thephthalazinium-2-methanide 1,3-dipole 1.This contains amore rigid structural component than the analogous cin-namaldehyde iminium¡Ómethanide dipole 3 and we wishedto compare the behaviour of 1 with this more exiblestructure 3.N+NCH2¡V1Ph N+CH2Ar3 ( EZ)In the generation of 1,3-dipoles from iminium salts thepossible EZ stereochemistry of the trimethylsilylmethyliminium triate salts has not been commented on, sincethese salts were generally not isolated in earlier studies.In the present work with cinnamaldehyde imines the salts2 were readily isolated by stirring cinnamaldehyde N-aryl-imines with trimethylsilylmethyl triuoromethanesulfonatein diethyl ether and varying mixtures of the EZ and EEforms were obtained (Scheme 1; Table 1, entries 1¡Ó5).The ratios were readily established by the 1H NMRspectra which showed the styryl a-CH (a doublet ofdoublets) more upeld when in the shielding region ofthe N-aryl ring in the EZ form (Scheme 1).When thesalts 2 were desilylated in the presence of the dipolaro-philes dimethyl acetylenedicarboxylate (DMAD), N-( p-substituted phenyl)maleimides, dimethyl fumarate anddimethyl maleate, the respective products 4, stereoisomerpairs 6,7, 12,13, 14,15 (all 1:1 ratio) and 10,11 (1:1 ratio)were obtained in high yields (Table 1).Interestingly theratio of EZ and EE isomers in the dipole precursor 2did not inuence the stereoisomer ratio of the cyclo-adducts, suggesting that the same dipole 3 (EE or EZ)enters the cycloaddition from either precursor.The 2,5-dihydropyrrole derivatives 4 and the pyrrolidine derivatives8¡Ó11 could be readily oxidised to 2-styrylpyrroles 5 withPbO2 in CH2Cl2. The product series 6, 7, 12¡Ó15 are new6-styryl-substituted 3,7-diazabicyclo[3.3.0]octane-2,4-diones.In all cases the isomeric pairs were readily separated bycolumn chromatography.All the compounds gave the expected microanalyses andIR and 1H and 13C NMR spectra with the required splittingpatterns (Scheme 1 and Experimental section). The stereo-isomers were distinguished by the NOE eects of the pyrro-lidine 2- and 3-H atoms when these were cis and theabsence of this NOE eect when these H atoms were trans(5-H and 6-H in products 6, 7, 12¡Ó15).In the exo cyclo-adducts 7, 13 and 15 the 6-CH was also signicantly moreshielded when cis to the imido p-electrons, a feature wehave also noted10 for the C-10a bridgehead hydrogen incycloadducts from the dipole 1. Varying and unequalendo:exo ratios were formed10 in the cycloadditions of thedipole 1.The consistent 1:1 ratio of stereoisomers observedherein with the dipole 3 probably reects the lower stericJ. Chem. Research (S),1998, 82¡Ó83$XN+ PhHCH2SiMe3¡ETfO¡VHH6.518.239.20CH2SiMe3¡ETfO¡VN+ PhHHH7.238.338.822 ( EZ) 2 ( EE)X+NCO2Me CO2MeHH HC6H4X- pPh6.106.685.444.394.6343NCO2Me CO2MeC6H4X- pPh5NC6H4Br- pPh8 X = W = CO2Me; Y = Z = H9 X = W = H; Y = Z = CO2Me10 X = Z = H; Y = W = CO2Me11 X = Z = CO2Me; Y = W = HX ZY WH1 23 45N HHPh C6H4X- pH HN OOC6H4Y- p+ii iiiviN HHPh C6H4X- pHH HNOO C6H4Y- p5.133.54123456 783.68 3.754.02H3.54 3.724.194.723.916 Y = H12 Y = OMe14 Y = Br7 Y = H13 Y = OMe15 Y = BrX = a, MeO; b, Me; c, H; d, Br; e, Cliiv or vabviFig. 1 Reagents: i. CsF; (ii) MeO2C¡ÓC==C¡ÓCO2Me; iii, p-substitutedphenylmaleimide; iv, dimethyl fumarate; v, dimethylmaleate; vi, PbO2in CH2Cl2; some key1HNMR shifts (CDCl3) are shownforX = Br$This is a Short Paper as dened in the Instructions for Authors,Section 5.0 [see J. Chem.Research (S), 1998, Issue 1]; there is there-fore no corresponding material in J. Chem. Research (M).*To receive any correspondence.82 J. CHEM. RESEARCH (S), 1998strain and greater exibility in the cycloaddition transitionstate.ExperimentalMps were measured on an Electrothermal apparatus. IR spectrawere measured with a Perkin Elmer 983G spectrophotometer. NMRspectra were measured on JEOL GX FT270 and GXFT400 spec-trometers using CDCl3 as solvent. Cinnamaldehyde N-aryliminesseparated on cooling after a dry EtOH solution of the aldehyde andthe p-substituted aniline (1:1 mol) was heated under reux for 1 h.The salts 2 were obtained in 90¡Ó95% yields when equimolar quan-tities of the imine and trimethylsilylmethyl triate were stirred indry Et2O at ambient temperature for 12 h.Cycloadditions (Typical Examples).3,7-Diphenyl-6-exo-[(E)-styryl]-3,7-diazabicyclo[3.3.0]octane-2,4-dione 7c and the endo isomer6c (Table 1, entry 7).A solution of the triate salt 2c (0.50 g, 1.38mmol) in dry CH2Cl2 (20 cm3) was treated with N-phenylmaleimide(0.48 g, 2.76 mmol) followed by an excess of CsF.The mixture wasstirred under anhydrous conditions at ambient temperatures for 24h and then ltered. The ltrate (together with the CH2Cl2 lter-cakewashings) was evaporated under reduced pressure to 4 cm3, placedon a column of silica gel (230¡Ó400 mesh) and eluted slowly withCH2Cl2. First eluted was the endo isomer 6c (40%) mp 198¡Ó200 8C(from MeOH) (Found: C, 79.0; H, 5.5; N, 7.0.C27H22NO2 requiresC, 79.2; H, 5.6; N, 7.1%) max/cm£¾1 (mull) 1709 br (amido C1O;dH(CDCl3) 3.54 (d, J 7.3 Hz, H-5), 3.64¡Ó3.79 (m, 2 H, H-1,H-8endo), 4.08 (d, J 9.5 Hz, H-8exo), 5.19 (d, J 6.6 Hz, 1 H, H-6),6.08¡Ó6.16 (dd, 1 H, styryl, Ha), 6.62 (d, J 15.4 Hz, 1 H, styryl, Hb),6.74¡Ó6.8 (m, 3 H, Ar), 7.21¡Ó7.49 (m, 12 H, Ar); dC (CDCl3) (o-res)43.6 (d, C-1), 49.6 (t, C-8), 51.5 (d, C-5), 63.3 (d, C-6), 145.1, 115.1,128.5, 118.7 (N-7-Ph, C-1', C-2', C-3', C-4' resp.), 135.9, 126.6,129.3, 125.7 (styryl phenyl, C-1', C-2', C-3', C-4' resp.), 131.5, 126.5,128.7, 128.2 (N-3-Ph, C-1', C-3', C-4' resp.), 128.9 (d, styryl C-a),133.2 (d, styryl C-b), 176.8, 177.9 (s, C1O).Next eluted was the exo isomer 7c (40%), 173¡Ó174 8C (fromMeOH) (Found: C, 79.1; H, 5.4; N, 6.9.C27H22NO2 requires C,79.2; H, 5.6; N, 7.1%); max/cm£¾1 (mull) 1712 br (amido C1O); dH(CDCl3) 3.68¡Ó3.76 (m, 2 H, H-8endo, H-1), 3.85¡Ó3.92 (m, 1 H, H-5),4.23¡Ó4.26 (m, 1 H, H-8exo), 4.75 (m, 1 H, H-6), 6.17¡Ó6.26 (dd, J16.1, 5.9 Hz, 1 H, styryl, H-a), 6.56 (d, 1 H, styryl, Hb), 6.78¡Ó6.86(m, 3 H, Ar), 7.03¡Ó7.07 (2 H, m, Ar), 7.22¡Ó7.30 (10 H, m, Ar); dC(CDCl3) (o-res). 44.9 (d, C-1), 49.9 (d, C-5) 50.9 (t, C-8), 62.3 (d,C-6), 146.4, 115.3, 128.6, 119.1 (N-7-Ph, C-1', C-2', C-3', C-4' resp.),135.9, 126.6, 129.2, 126.8 (styryl phenyl C-1', C-2', C-3', C-4' resp.),131.6, 124.9, 129.2, 128.1 (N-3-Ph, -1', C-2', C-3', C-4' resp.), 128.7(d, styryl C-a) 133.1 (d, styryl, C-b), 174.8, 177.3 (s, C1O).1-(p-Bromophenyl)-3,4-bis(methoxycarbonyl)-2-[(E)-styryl]-2,5-dihy-dropyrrole 4d and -pyrrole 5d (Table 1, entry 4).¡ÓA solution of thetriate salt 2d (0.50 g, 1.13 mmol) in dry CH2Cl2 (20 cm3) wastreated with dimethyl acetylenedicarboxylate (0.28 ml, 2.6 mmol)followed by an excess of CsF.The mixture was stirred under anhy-drous conditions at ambient temperatures for 24 h and then ltered.The ltrate (together with the CH2Cl2 lter-cake washings) wasevaporated under reduced pressure to 4 cm3, placed on a ash col-umn of silica gel (230¡Ó400 mesh ASTM) and eluted with gradientmixtures of petroleum spirit (bp 40¡Ó60 8C)¡ÓCH2Cl2 (1:0 to 1:1) togive the dihydropyrrole 4d (80%), mp 164¡Ó166 8C (from EtOH)(Found C, 59.5; H, 4.7; N, 3.1.C22H20BrNO4 requires C, 59.7; H,4.5; N, 3.1.1%); max/cm£¾1 (mull) 1725, 1730 (ester C1O); dH(CDCl3) 3.81 (s, 3 H, CO2Me), 3.85 (s, 3 H, CO2Me), 4.39 (dd, 1 H,H-5 trans relative to styryl), 4.63 (dd, 1 H, H-5 cis), 5.44 (m, 1 H,H-2), 6.10 (dd, 1 H, styryl, H-a), 6.49¡Ó6.53 (m, 2 H, N-ArBr), 6.68(d, J 16.1 Hz, 1 H, styryl, H-b), 7.27¡Ó7.32 (m, 7 H, Ar); dC (CDCl3)(o-res) 52.6 (q, OMe), 55.9 (t, C-5), 69.3 (d, C-2), 144.6, 113.9,132.0, 109.5 (N-1-p-BrC6H4,C-1', C-2', C-3', C-4' resp.), 139.9,126.8, 128.2, 126.2 (styryl phenyl, C-1', C-2', C-3', C-4' resp.), 132.4(s, C-4), 135.9 (s, C-3), 128.1 (d, styryl C-a), 135.9 (d, styryl, C-b),162.9, 163.5 (s, C1O).Oxidation of 4d (0.45 mmol) with PbO2 (4.5 mmol) in CH2Cl2(20 cm3) for 48 h at ambient temperate gave the pyrrole 5d (50%),mp 94¡Ó95 8C (from EtOH) (isolated by elution from a ash columnof silica gel 230¡Ó400 mesh ASTM with petroleum spirit (bp 40¡Ó60 8C¡ÓCH2Cl2 (20:1 v/v) (Found: C, 59.7; H, 4.0; N, 3.2.C22H18BrNO4 requires C, 60.0; H, 4.1; N, 3.2%); max/cm£¾1 (mull),1724, 1710 (ester C1O); dH (CDCl3) 3.85 (s, 3 H, OMe), 3.93 (s,3 H, OMe), 6.79 (dd, 2 H, N-1-p-BrC6H4, H-2'), 7.23¡Ó7.35 (m, 9 H,aromatic protons, styryl, Ha, Hb), 7.64 (m, 1 H, H-5); dC (CDCl3)(o-res.), 51.7, 52.4 (q, OMe), 137.5, 115.3, 132.9, 116.3 (N-1-p-BrC6H4, C-1', C-2', C-3', C-4' resp.), 136.5, 127.8, 128.7, 126.5(styryl phenyl, C-1', C-2', C-3', C-4' resp.), 122.6 (s,C-4), 127.9 (s,C-3), 128.0 (d, styryl, C-a), 128.5 (d, styryl, C-b), 132.7 (C-2), 133.5(d, -5), 163.8, 166.3 (s, C1O).The 1-(p-methoxyphenyl) pyrrole 5a, mp 104¡Ó106 8C (fromEtOH), was similarly obtained.Received, 16th September 1997; Accepted, 8th October 1997Paper E/7/06737BReferences1 I.Coldham, A. J. Collis, R. J. Mould and D. E. Robinson,Synthesis, 1995, 1147.2 For a review see, J. W. Lown, in 1,3-Dipolar CycloadditionChemistry, ed. A. Padwa, Wiley, New York, 1984, vol. 1, p. 653.3 A. Padwa and L. Hamilton, Tetrahedron Lett., 1965, 4363;C. Wittland, M. Arend and N. Risch, Synthesis, 1996, 367.4 Y. Gelas-Mialhe, E. Tourad and R. Vessiere, Can. J. Chem.,1982, 60, 2830; R.Grigg, J. Montgomery and A.Somasunderam, Tetrahedron, 1992, 48, 10431.5 O. Tsuge, S. Kanemasa, M. Ohe, K. Yorozu, S. Takenaka andK. Ueno, Bull. Chem. Soc. Jpn., 1987, 4067; O. Tsuge, S.Kanemasa, M. Ohe and S. Takenaka, Chem. Lett., 1986, 973.6 J. Mortier and M. Joucla, Tetrahedron Lett., 1987, 27, 2973;J. E. Baldwin, S. C. MacKenzie Turner and M. G. Moloney,Synlett., 1994, 925.7 H. Ardill, X. L. R. Fontaine, R. Grigg, D. Henderson, J.Montgomery, V. Sridharan and S. Surendrakumar, Tetrahedron,1990, 46, 6449.8 E. Vedejs, S. Larsen and F. G. West, J. Org. Chem., 1985, 50,2170; E. Vedejs and F. G. West, Chem. Rev., 1986, 86, 941.9 R. C. F. Jones, J. R. Nichols and M. T. Cox, Tetrahedron Lett.,1990, 31, 2333.10 R. N. Butler, D. M. Farrell and C. S. Pyne, J. Chem. Res. (S),1996, 418.Table 1 Substrates and cycloadductsMpa Yield Mpa YieldEntry Compd. (T 8/C) (%) dH Compd. (T 8/C) (%) dH1 2a 158^159b 95(4:1)d ^ 4ah 143^145 88 5.38g2 2b 163^164b 93(1.5:1) ^ 4b 104^106 63 5.41g3 2c 135^137b 92(1:3) ^ 4c 99^100 60 5.45g4 2d 156^158b 90(1.2:1) ^ 4dh 164^166 80 5.44g5 2e 146^148b 90(1:1) ^ 4e 154^155 80 5.40g6 6d 99^100 40 5.13e,f 7d 174^175 40 4.72e7 6c 198^200c 40 5.19e,f 7c 173^174c 40 4.75e8 12d 120^122 30 5.10e,f 13d 190^192 30 4.71e9 14d 178^180 46 5.09e,f 15d 152^154 46 4.70e10 8 84^85 35 4.58f,g 9h 88^89 35 4.66g11 10 124^126 20 4.59g 11 130^132 20 4.62f,gaFrom EtOH unless stated otherwise. bWashed with Et2O. cFrom MeOH. dParentheses contain EZ:EE ratio. eH for H-6. fNOE enhancementfrom adjacent cis H. gH for H-2. hOxidation gave compounds 5a and 5d.J. CHEM. RESEARCH (S), 1998 83

ISSN:0308-2342    

DOI:10.1039/a706737b

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

3-(2,2-Dicyano-1-methylvinyl)coumarin in HeterocyclicSynthesis: Synthesis of Some New CoumarinDerivatives{Mohamed R. SelimDepartment of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, Cairo, EgyptThe reaction of 3-acetylcoumarinwith activated nitriles provides a convenient route to a range of newcoumarin derivatives.Cyanocoumarins are of considerable interest as potentialbuilding blocks for nitrogen-containing heterocyclic systems.In addition to the study of the behaviour of a variety ofaromatic or heterocyclic amino compounds with activatednitriles, interest has been shown in coumarin derivatives onaccount of their pharmacological activity.1¡Ó3 In continuationof our work4¡Ó7 on coumarins, we sought to synthesize newcoumarin derivatives which might be biologically active.Thus condensation of 3-acetylcoumarin (1) with malono-nitrile in boiling benzene containing ammonium acetate andacetic acid using a Dean¡ÓStark water separator aorded 3-(2,2-dicyano-1-methylvinyl)coumarin (2)8 (Scheme 1).In contrast to the anticipated formation of pyrazolinederivatives 3,9 the reaction of 2 with phenylhydrazine inboiling ethanol gave the imino compound 4.This is assumedto proceed via elimination of malononitrile. The suggestedstructure for 4 was conrmed by its independent synthesisfrom 1 on reuxing with phenylhydrazine in boiling etha-nol10 (Scheme 1).Interaction of 2 with primary aromatic amines in boilingethanol aorded 3-(2,2-dicyano-1-arylamino-1-methylethyl)-coumarins (5a¡Ód) resulting from initial attack of the nucleo-phile at C-b of the olenic bond of the dicyano derivatives(Scheme 1).Reaction of 2 with sulfur in a Gewald reaction11produced 3-(5-amino-4-cyano-3-thienyl)coumarin (6). Inter-action of 6 with maleic anhydride in a Diels¡ÓAlder reactionfurnished 7, while its acetylation produced the correspond-ing acylated compound 8 (Scheme 1).Passing hydrogensulde gas into a solution of 2 in ethanol containing afew drops of triethylamine aorded 3-(2-cyano-1-methyl-2-thiocarboxamidovinyl)coumarin (9) (Scheme 1).Condensation of 2 with various substituted a-cyano-cinnamonitriles 10a¡Óc in boiling ethanol containing a fewdrops of piperidine produced 3-(3-amino-2,4-dicyano-5-aryl-phenyl)coumarins 13a¡Óc (Scheme 2).These are assumed tobe formed via Michael addition of the methyl function in 2to the activated double bond in 10, yielding the adduct 11which then cyclizes into 12, the latter readily losing hydro-gen cyanide to yield the stable compound 13. In contrast tothe anticipated formation of the ester 14, the reaction of 2J.Chem. Research (S),1998, 84¡Ó85$R MeNNHPh4R CCNCNN HNHPhMe R Me3N NNH2PhNH¡VH2CCNCNR MeO1RR MeH2CCNCNMeNC CNH2S2NCSNH2PhNHNH2 PhNHNH2 PhNHNH2R6SNCNH2 RC5CNCNMeNHR¢Fa R¢F = Phb R¢F = C6H4NH2-2c R¢F = C6H4Cl-2d R¢F = C6H4Me-4R8SNCNHAcR7OH2NNCOOO O OAc2ORNH2TEASR =O O9Scheme 1R ArCNCO2EtNC CN2 + ArCH CCNX10a Ar = Ph, X = CNb Ar = C6H4Me-4, X = CNc Ar = C6H4OMe-4, X = CNd Ar = Ph, X = CO2Ete Ar = C6H4NO2-4, X = CO2EtR ArCNCNNC CN11aR ArCNCO2EtNC12b 12aR ArCO2Et NC14R ArCN NC13a Ar = Phb Ar = C6H4Me-4c Ar = C6H4OMe-4d Ar = C6H4NO2-4NHR HCNCNNCNHArNH2 NH2H11bScheme 2 Ras in Scheme1$This is a Short Paper as dened in the Instructions for Authors,Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there-fore no corresponding material in J. Chem. Research (M).84 J. CHEM. RESEARCH (S), 1998with 10d,e aorded 13a,d, presumably via elimination ofethyl formate from the intermediate 12b (Scheme 2).ExperimentalMps are uncorrected. Elemental analyses were carried out in themicroanalytical laboratories of the Faculty of Science, CairoUniversity.IR spectra (KBr) were measured on a Shimadzu IR 440spectrophotometer. 1H NMR spectra were recorded on a JEOL FX90Q (90 MHz) spectrometer and mass spectra on a Shimadzu GC-MS-QPm 1000 EX spectrometer using the direct-inlet system.3-(2,2-Dicyano-1-methylvinyl)coumarin (2).To a solution of 3-acetylcoumarin 1 (0.1 mol) in dry benzene (10 ml) was addedmalononitrile (0.1 mol), ammonium acetate (2 g) and acetic acid(2 ml).The reaction mixture was heated under reux using a Dean¡ÓStark water separator until water ceased to be collected. The pro-duct obtained was crystallized from ethanol to give the title com-pound 2, (85%), mp 155 8C, max/cm£¾1 2200 (CN), 1720 (C1O),1620 (C1C); H ([2H6]DMSO) 2.7 (3 H, s, CH3), 7.7¡Ó8.3 (4 H, m,ArH), 8.9 (1 H, s, H-4) (Found: C, 71.30; H, 3.40 C14H8N2O2requires C, 71.18, H 3.38%).3-[1-(Phenylhydrazonoethyl]coumarin (4).A mixture of 1 or 2(0.01 mol) and phenylhydrazine (0.01 mol) in ethanol (30 ml) washeated under reux for 2 h. The reaction mixture was cooled togive a solid which was ltered o and crystallized from ethanol togive the title compound 4 (80%), mp 180 8C, max/cm£¾1 3484, 3298(NH), 1720 (C1O), 1601 (C1); H (CDCl3) 2.50 (3 H, s, CH3),7.5¡Ó8.8 (9 H, m, ArH), 8.9 (1 H, s, H-4) and 9.3 (1 H, br, NHexchangeable with D2O) (Found: C, 73.20; H, 4.90 C17H14N2O2requires C, 73.38, H, 5.03%).Reaction of 3-(2,2-Dicyano-1-methylvinyl)coumarin (2) with Aro-matic Amines.To a solution of 2 (0.01 mol) in ethanol (30 ml) wasadded the amine (0.01 mol) in ethanol (30 ml) in portions.The mix-ture was heated under reux for 2 h and then left to cool. The pre-cipitated product was ltered o, dried and crystallized fromethanol to give 3-(2,2-dicyano-1-arylamino-1-methylethyl) coumarins5a¡Ód.The anilino compound 5a (60%) had mp 142 8C, max/cm£¾1 3440(NH), 3050, 2965, 2220 (CN), 1715 (C1O); dH (CDCl3) 2.7 (3 H, s,CH3), 2.8 (1 H, s, CH), 7.5¡Ó8.6 (9 H, m, ArH), 8.9 (1 H, s, H-4)and 9.2 (1 H, br, NH exchangeable with D2O) (Found: C, 72.54; H,4.60. C20H15N3O2 requires C, 72.94; H, 4.55%).The 2-aminophenylamino compound 5b (55%) had mp 130 8C,max/cm£¾1 3430, 3350 (NH2, NH), 2930, 2230 (CN), 1725 (C1O);dH (CDCl3) 2.6 (3 H, s, CH3), 2.9 (1 H, s, CH), 5.3 (2 H, br, NH2),7.4¡Ó8.7 (8 H, m, ArH), 8.9 (1 H, s, H-4) and 9.3 (1 H, br, NH,exchangeable with D2O) (Found: C, 69.30; H, 4.30.C20H16N4O2requires C, 69.76; H, 4.65).The 2-chlorophenylamino compound 5c (58%) had mp 135 8C,max/cm£¾1 3440 (NH), 3040, 2960, 2210 (CN), 1700 (C1O); dH(CDCl3) 2.7 (3 H, S, CH3), 2.8 (1 H, s, CH), 7.6¡Ó8.8 (8 H, m,ArH), 8.8 (1 H, s, H-4), 9.4 (1 H, br, NH, exchangeable with D2O)(Found: C, 65.20, H, 3.50.C20H14ClN3O2 requires C, 66.02; H,3.85%).The p-tolylamino compound 5d (50%) had mp 140 8C, max/cm£¾13430 (NH), 2900, 2220 (CN), 1720 (C1O); dH (CDCl3) 2.6 (3 H, s,CH3), 2.7 (3 H, s, CH3), 2.8 (1 H, s, CH), 7.6¡Ó8.8 (8 H, m, ArH),8.9 (1 H, s, H-4), 9.3 (1 H, br, NH exchangeable with D2O)(Found: C, 73.80; H, 4.80. C21H14N3O2 requires C, 73.46, H,4.95%).3-(5-Amino-4-cyano-3-thienyl)coumarin 6.Equimolar amounts(0.01 mol) of 2 and elemental sulfur in ethanol (30 ml) were treatedwith a few drops of triethylamine (TEA).The reaction mixture washeated under reux for 2 h and then left to cool down to give asolid which was ltered o and crystallized from ethanol to give thetitle compound 6 (85%), mp 245 8C, max/cm£¾1 3472, 3332 (NH2),3056, 2211 (CN) and 1722 (C1O) (Found: C, 62.50; H, 2.80.C14H8N2O2S requires C, 62.68; H, 2.98%).3-Amino-4-cyano-5-(2-oxo-2H-chromen-3-yl) phathalic Anhydride7.A mixture of 6 (0.01 mol), maleic anhydride (0.01 mol) and1,4-dioxane (30 ml) was heated under reux for 3 h.On cooling, asolid formed which was ltered o and crystallized from ethanol togive the title compound 7 (70%), mp 212 8C; max/cm£¾1 3430, 3350(NH2), 3050, 2200 (CN), 1725 (C1O), 1650 (CO); H (CDCl3) 5.6(2 H, br, NH2 exchangeable with D2O), 7.6¡Ó8.6 (5 H, m, ArH),8.95 (1 H, s, H-4) (Found: C, 65.10; H, 2.50. C18H8N2O5 requiresC, 65.06; H, 2.40%).3-(5-Acetamido-4-cyano-3-thienyl)coumarin (8).A solution of 6(0.01 mol) in acetic anhydride (30 ml) was heated under reux for3 h.The reaction mixture was cooled to give a solid which wasltered o and crystallized from ethanol to give the title compound8 (85%), mp 266 8C; max/cm£¾1 3450 (NH), 3040, 2975, 2215 (CN),1705 (C1O), 1680 (C1O); H (CDCl3) 3.5 (3 H, s, CH3), 7.1 (1 H,s, CH), 7.5¡Ó8.7 (4 H, m, ArH), 9.1 (1 H, s, H-4), 9.4 (1 H, br, NH)(Found C, 62.10; H, 3.40. C16H10N2O3S requires C, 61.93; H,3.22%).3-(2-Cyano-2-methyl-2-thiocarboxamidovinyl)coumarin (9).A sol-ution of 2 (0.01 mol) in ethanol (30 ml) and a few drops of triethyl-amine was treated with hydrogen sulde gas for 2 h to give a solid,which was ltered o and crystallized from benzene to give the titlecompound 9 (75%), mp 183 8C; max/cm£¾1 3354, 3312 (NH2), 3113,2214 (CN), 1694 (C1O) (Found: C, 62.40; H, 3.80.C14H10N2O2Srequires C, 62.22; H, 3.70%).Reaction of 2 with Cinnamonitrile Derivatives 10a¡Óe.A suspen-sion of 2 (0.01 mol) in ethanol (30 ml) was treated with 10a¡Óe (0.01mol) and a catalytic amount of piperidine (0.1 ml).The reactionmixture was heated under reux for 2 h. The precipitate was lteredo and crystallized to give 3-(3-amino-2,4-dicyano-5-arylphenyl)-coumarins 13a¡Ód.The 5-phenyl compound 13a (70%) had mp 257 8C (from EtOH);max/cm£¾1 3472, 3332 (NH2), 3056, 2211 (CN), 1722 (C1O). dH(CDCl3) 5.4 (2 H, br, NH2 exchangeable with D2O), 7.6¡Ó8.8 (10 H,m, ArH), 8.9 (1 H, s, H-4); m/z 363 (M+, 100%), 336 (24), 335(30), 306 (7), 279 (9), 182 (6), 139 (7), 126 (8), 113 (7), 77 (6)(Found: C, 76.10; H, 3.70.C23H13N3O2 requires C, 76.03; H,3.58%).The 5-p-tolyl compound 13b (75%) had mp 268 8C (from EtOH);max/cm£¾1 3460, 3340 (NH2), 3050, 2220 (CN), 1715 (C1O); dH(CDCl3), 2.47 (3 H, s, CH3), 5.6 (2 H, br, NH2 exchangeable withD2O), 7.6¡Ó8.1 (9 H, m, ArH), 8.8 (1 H, s, H-4) (Found: C, 75.20;H, 4.30. C24H15N3O2 requires C, 76.39; H, 3.97%).The 5-(4-methoxyphenyl) compound 13c (80%) had mp 320 8C(from benzene); max/cm£¾1 3440, 3340 (NH2), 2950, 2210 (CN), 1715(C1O); dH (CDCl3) 4.2 (3 H, s, OCH3), 5.4 (2 H, br, NH2exchangeable with D2O), 7.3¡Ó8.5 (9 H, m, ArH), 8.9 (1 H, s, H-4)(Found: C, 73.20; H, 4.10.C24H15N3O3 requires C, 73.28; H,3.81%).The 5-(4-nitrophenyl) compound 13d (78%) had mp 310 8C (from1,4-dioxane), max/cm£¾1 3450, 3320 (NH2), 3010, 2220 (CN), 1720(C1O); dH (CDCl3), 5.6 (2 H, br, NH2 exchangeable with D2O),7.4¡Ó8.6 (9 H, m, ArH), 8.95 (1 H, s, H-4) (Found: C, 67.70; H,3.20. C23H12N4O4 requires C, 67.64; H, 2.94%).Received, 21st May 1997; Accepted, 8th October 1997Paper E/7/03506CReferences1 Comprehensive Heterocyclic Chemistry, ed. A. R. Katritzky andC. W. Rees, Pergamon, Oxford, 1984, vol. 1, p. 151 and vol. 3,p. 881.2 N. A. Stalmann, C. F. Huenter and K. P. Link, J. Biol. Chem.,1941, 138, 513.3 J. O. Berdy, Heterocyclic Antibiotics, CRC Press, Boca Raton,1981.4 M. R. Selim, A. M. El-Agrody, A. H. Bedair and F. M. Aly,Sci. Phys. Sci., 1990, 100.5 M. R. Selim, A. M. El-Agrody, A. H. Bedair, F. M. Aly andM. F. Hassan, Egypt. J. Chem., 1992, 369.6 M. R. Selim, F. A. Abu-Shanab, F. M. Aly and A. H. Bedair,J. Indian Chem. Soc., 1992, 688.7 M. R. Selim, H. A. Emam, A. M. Radwan and A. Z. Sayed,Proc. Indian Natl. Sci. Acad., 1996, 62, 429.8 M. Coenen, Leibigs Ann. Chem., 1960, 85, 640.9 S. Abdou, S. M. Fahmy, M. M. Khader and M. H. Elnagdi,Monatsh. Chem., 1982, 113, 985.10 A. H. Bedair, F. M. Aly and A. M. El-Agrody, J. Serb. Chem.Soc., 1986, 51, 213.11 K. Gewald, Chem. Ber., 1965, 98, 357.J. CHEM. RESEARCH (S), 1998 85

ISSN:0308-2342    

DOI:10.1039/a703506c

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Synthesis and Characterization of Na5H(CN2)3{ Michael Becker andMartin Jansen* Institut fu �á rAnorganische Chemie der Universita�á t Bonn, Gerhard-Domagk-Str.1, Bonn D-53121, Germany Single phase Na5H(CN2)3 was obtained by thermal decomposition of Na(HNCN) and structurally characterized by Rietveld refine- ment of X-ray powder diffraction data; Na5H(CN2)3 was found to be isostructural to K5H(CN2)3, and identical to a phase that was previously reported as `Na4H2(CN)3`. Up to now two sodium salts of cyanamide, Na(HNCN) and Na2(NCN),1 have been identiRed and structurally character- ized.Both substances are highly sensitive to the atmosphere. Another sodium salt of cyanamide, `Na4H2(CN2)3' was reported in 1989.2 However, the powder di€ractogram cal- culated for the proposed structure shows signiRcant devi- ations from the experimental one, and a reinvestigation seemed worthwhile. Results The title compound was synthesized using the procedure previously reported for `Na4H2(CN2)3'.2 A crystal structure determination by Rietveld's proRle Rtting method based on X-ray powder data revealed the true composition to be Na5H(CN2)3.The crystal data and atomic parameters are given in Table 1. On comparing the experimental X-ray powder di€ractograms it became quite clear that the pre- viously published `Na4H2(CN2)3' and Na5H(CN2)3 are iden- tical. Using the right composition and structural model, the signiRcant discrepancies between the calculated and observed X-ray powder di€ractograms disappear (cf.Fig. 1). Furthermore, empty octahedral voids, an unreasonable fea- ture of the previous structural model, are now occupied by sodium with interatomic distances as one would expect. Na5H(CN2)3 is isostructural to K5H(CN2)3.3 Discussion The structure of Na5H(CN2)3 consists of two inter- penetrating ReO3-analogous sublattices with the com- positions Na(CN2)3 which are shifted with respect to each J. Chem. Research (S), 1998, 86�}87$ Table 1 Crystallographic parameters for Na5H(CN2)3, average deviation in brackets Na5H(CN2)3 (a) Crystal data Symmetry cubic Space group lm 3m a/pm 724.49(9) (b) Atomic co-ordinates: x, y, z Na(1) 0 0 0 Na(2) 0.25 0.25 0.25 C 0.500 N 0.339(1) 0 0 (c) Interatomic distances [pm] r[Na(1)^N] 266.6(2) r[Na(2)^N] 255.0(71) r[Na(1)^Na(2)] 313.71 r[C_N] 107.2(71) (d) interatomic angles [ 8] N�}C�}N 180 Na(1)�}N�}C 180 N�}Na(1)�}N (12 times) 90 N�}Na(1)�}N (3times) 180 N�}Na(2)�}N (6 times) 94.87(217) N�}Na(2)�}N (6 times) 85.13(217) N�}Na(2)�}N (3times) 180 Na(2)�}N�}C 106.09(147) Fig. 1 X-Ray powder pattern and difference plot after Rietveld refinement of Na5H(CN2)3 $This is a Short Paper as deRned in the Instructions for Authors, [J. Chem. research (S), 1997, Issue 1, p. vii]; there is therefore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 86 J. CHEM. RESEARCH (S), 1998other by the vector (0.5/0.5/0.5).Each resulting octahedralhole is occupied by sodium. Thus Na(1)+ is found in aregular, octahedral coordination sphere formed by CN2 2£¾ligands [r(Na(1)+¡ÓN)= 266.6 pm; Na(1)+¡ÓN¡ÓC= 180 8](Fig. 2).Na(2)+ shows a slight deviation from a regular octahedralcoordination [r(Na(2)+¡ÓN)= 255.0 pm; Na(2)+¡ÓN¡ÓC=106.09 8]. Pertinent crystallographic data, including inter-atomic distances and angles, are collected in Table 1. Theprotons in Na5H(CN2)3 are disordered. At the level ofsignicance of the present structure determination, no devi-ations in the geometry of (N¡ÓC¡ÓN)2£¾, which might becaused by attached hydrogen atoms, are found.ExperimentalThe monosodium salt of cyanamide was synthesized from a sol-ution of the free acid in rigorously dried ethanol using sodiumethoxide as a base.Na5H(CN2)3 was obtained as the residueremaining after thermal treatment of Na(HNCN) under vacuum(275 K; 0.1 Nm£¾2; 12 h).2 The samples obtained were colourless,polycrystalline and, according to X-ray powder diraction, free ofalien phases. The experimental data were collected on a Stoe StadiP diractometer using a Germanium monochromator with CuKaradiation (l=1.54051 A ). The structure renement was carried outby Rietveld methods4,5 out of 15 reections with 2 y in the range 10to 80 8. The residual value for the renement converged toR(p) =0.095 and R(i ) = 0.082.Received, 26th August 1997; Accepted, 9th October 1997Paper 7/06196JReferences1 M. G. Down, M. J. Haley, P. Hubberstey, R. J. Pulham andA. E. Thunder, J. Chem. Soc., Chem. Commun, 1978, 52.2 A. Harper and P. Hubberstey, J. Chem. Res., 1989, (S) 194;(M) 1452.3 M. Becker, M. Jansen, A. Lieb, W. Milius and W. Schnick,Z. Anorg. Allg. Chem., in the press.4 H. M. Rietveld, Acta Crystallogr., 1967, 22, 151.5 H. M. Rietveld, Acta Crystallogr., 1969, 2, 65.Fig. 2 Unit cell of Na

ISSN:0308-2342    

DOI:10.1039/a706196j

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Lewis Acid-catalysed Facile Elimination of the DiazoGroup in 3-Diazochromanones. Novel Conversion ofChromanones into Chromones{Pranab Mandal and Ramanathapuram V. Venkateswaran*Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta-700 032, India3-Diazochromanones undergo rapid elimination of the diazo group in presence of BF3Et2O to furnish chromones.The ready accessibility of a-diazocarbonyl compounds andthe versatility of their transformations have made them oneof the most useful functional groups in organic synthesis;1the wide variety of a-diazocarbonyl compounds which havebeen brought within the scope of such transformations attestto the immense potential of this functional group.However,extension of such varied transformations to carbocyclicdiazoketones has been rather limited and there has been noreport of any transformation involving the 3-diazo-4-chromanone system. As an extension of our continuing syn-thetic studies involving chromone precursors,2 we have alsostarted investigations into the possible utilisation of 3-diazo-chromanones and herein report the facile elimination ofthe diazo group in the presence of BF3Et2O to furnish chro-mones (Scheme 1).The 3-diazochromanones were preparedfrom the corresponding chromanones via a formylation anddeformylative diazo transfer reaction and were obtained inoverall yields of 55¡Ó60%. Treatment of these diazo-chromanones (2a¡Óe) with a catalytic amount of BF3Et2O inmethylene chloride at ambient temperature for 1¡Ó1.5 h furn-ished the chromones 3a¡Óe, respectively, in excellent yields,providing a new procedure for the conversion of chroma-nones into chromones (Table 1).3 The structures of theproducts were established through detailed spectral analysisand comparison with authentic samples.When methanolwas added to the reaction medium, 2a aorded a mixture ofchromone 3a and 3-methoxychromanone (4a, Scheme 1), invarying proportions, and when methanol alone was used asthe solvent, it gave 4a exclusively in more than 85% yield.Similarly, in presence of allyl alcohol, the allyl derivative 4bwas obtained in very good yield.This suggests a route tovarious 3-alkoxy substituted chromanones.When this diazo elimination reaction was extended to thealicyclic situation, as in 2-diazotetralin-1-one, it furnished a-naphthol in over 70% yield as a result of elimination andconsequent aromatisation.The metal-catalysed decomposition of a diazoketone con-taining an a-hydrogen has been reported to lead to analkene, depending on the nature of the ligand on the metal.1In keeping with this, decomposition of 3-diazochromanone2a with a catalytic amount of dirhodium tetraacetate inbenzene furnished chromone 3a in more than 70% yield.In summary, we describe an interesting Lewis acid-catalysed elimination of the diazo group in 3-diazo-chromanones as a novel route to chromones.This shouldserve as a useful complementary procedure to other existingmethods for the transformation of chromanones intochromones.3ExperimentalGeneral Procedure as Illustrated for 3a.To a stirred slurry ofsodium hydride (1.44 g) in diethyl ether (40 ml) under nitrogen wasadded a drop of ethanol followed by a solution of chromanone (1a)(2.96 g) in diethyl ether (5 ml). The reaction mixture was cooled inan ice-bath and ethyl formate (4.44 g) was added dropwise, and themixture stirred overnight.The reaction mixture was then pouredinto ice-cold water, the diethyl ether layer separated and theaqueous layer acidied with cold dil. HCl and extracted with diethylether. The ethereal extracts were combined, washed with brine,dried (Na2SO4) and concentrated to aorded the 3-formyl-chromanone (2.95 g, 83%) which was used directly in the next step.The above formylchromanone was dissolved in methylenechloride (20 ml) and triethylamine (3.75 g) was added.The reactionmixture was cooled in an ice-bath and a solution of toluene-p-sulfonyl azide (7.3 g) in methylene chloride (5 ml) was added drop-wise. The cold reaction mixture was stirred for 3 h and subsequentlyovernight at room temp. Aqueous potassium hydroxide (10%,20 ml) was then added and the solution stirred for 30 min. Thelayers produced were separated and the aqueous layer extractedwith diethyl ether. The combined organic extracts were washed withaqueous potassium hydroxide (5%) and water, and then dried(Na2SO4). Removal of the solvent followed by chromatography ofthe oily residue over neutral alumina (benzene¡Ólight petroleum, bp40¡Ó60 8C, 2:3) furnished the 3-diazochromanone 2a (2.1 g, 72%)as a yellow solid, mp 52¡Ó55 8C; max/cm£¾1 2100, 1670; dH (ppm)(CDCl3, 60 MHz) 5.22 (s, 2 H), 7.0¡Ó7.52 (m, 3 H), 7.96 (d, 1 H,J 8 Hz).Compound 2a (1 g) was taken in methylene chloride (5 ml) and adrop of boron triuoride etherate was added by syringe.The reac-tion mixture was stirred for 1.5 h at room temp.and decomposedwith aqueous NaHCO3. The organic layer was separated and theaqueous layer extracted with diethyl ether. The combined organicextracts were washed with water, dried and the solvent distilled o,to furnish chromone 3a (0.79 g, 95%) in satisfactorily pure form,identical with an authentic sample.Table 1 lists the physical data and yields of the diazochroman-ones 2a¡Óe and the products 3a¡Óe.Formation of 3-Methoxychromanone (4a) from 3-Diazochromanone(2a).The above reaction was carried out using methanol assolvent in place of methylene chloride.After 1.5 h the reactionmixture was decomposed with aqueous NaHCO3 and extracted withJ. Chem. Research (S),1998, 88¡Ó89$OR1R2OR3 OR1R2OR3N21 2OR1R2OR33OOOR4ia R1 = R2 = R3 = Hb R1 = Me, R2 = R3 = Hc R1 = R3 = H, R2 = Med R1 = H, R2 = R3 = Mee R1 = R3 = H, R2 = OMea R = Meb R = CH2¡VCH CH2iiiii1¡V3Scheme 1 Reagents: i, (a) NaH/HCO2Et/Et2O (b) Et3N/TsN3;ii, BF3.Et2O/CH2Cl2; iii, (a) BF3.Et2O/MeOH (b) BF3.Et2O/CH2=CH£¾CH2£¾OH$This is a Short Paper as dened in the Instructions of Authors[J.Chem. Research (S), 1997 Issue 1, p. xi], there is therefore nocorresponding material in J. Chem. Research (M).*To receive any correspondence..88 J. CHEM. RESEARCH (S), 1998Table 1 Y|elds andmps of diazochromanones 2a^e and product chromones 3a^e Diazochromanone Mp (8C) Yield (%)a Product Yield (%) Mp (lit.) (8C) 2a 52^55 (60) 3a 95 59 (594) 2b 85^88 (58) 3b 95 87^88 (88^895) 2c 118^120 (60) 3c 95 84^86 (725)b 2d 109^110 (55) 3d 90 98^99 (984) 2e 114^116 (60) 3e 90 110 (1106) aOverall yield for the two steps of formylation and diazotransfer.bThe Mpdiffered from that reported, possibly due to better purity of present sample. Spectral data corroborated the structure. diethyl ether. The ethereal extracts were washed with water, dried (Na2SO4) and the residual oil, after removal of diethyl ether, was distilled to furnish 3-methoxychromanone (4a, 880 mg, 86%), bp (bath temperature) 115�}18 8C (5 mmHg); H (CCl4, 60MHz) 3.50 (s, 3 H), 3.73 (t, 1 H, J 5 Hz), 4.4 (d, 2 H, J 5 Hz), 6.8�}7.5 (m, 3 H), 7.76 (d, 1 H, J 8 Hz) (Found: C, 67.23; H, 5.65.C10H10O3 requires C, 67.40; H, 5.66%). Using allyl alcohol in the above experiment a€orded the 3-allyl- oxychromanone 4b in 80% yield; bp (bath temperature) 125�}126 8C (5 mmHg); dH (CDCl3, 300 MHz) 4.11�}4.21 (m, 2 H), 4.34�}4.48 (m, 3 H), 5.21�}5.36 (m, 2 H), 5.91�}6.14 (m, 1 H), 6.95�}7.06 (m, 2 H), 7.45�}7.51 (m, 1 H), 7.88 (d, 1 H, J 9 Hz); dC 69.67, 71.82, 74.47, 117.67, 118.37, 119.76, 121.63, 127.42, 133.65, 136.06, 161.08, 190.95 (Found: C, 70.24; H, 6.28.C12H12O3 requires C, 70.57; H, 5.92%). We sincerely thank the Department of Science and Technology, New Delhi, for Rnancial support. P.M. thanks the UGC, New Delhi, for a fellowship. Received, 30th July 1997; Accepted, 17th October 1997 Paper E/7/05517J References 1 For a review, see T. Ye and M. A. McKervey, Chem. Rev., 1994, 94, 1091. 2 (a) J. Mal, A. Nath and R. V. Venkateswaran, J. Org. Chem., 1996, 61, 9164; (b) A. Nath, J. Mal and R. V. Venkateswaran, J. Org. Chem., 1996, 61, 4391; (c) A. Nath, A. Ghosh and R. V. Venkateswara1992, 57, 1467. 3 For other methods of synthesis of chromones from chromanones, G. Shanker, B. V. Malliaiah and G. Srimanyarayana, Synthesis, 1983, 311 and references cited therein. 4 B. K. Ganguly and P. Bagchi, J. Org. Chem., 1956, 21, 1415. 5 Dictionary of Organic Compounds, Eyre and Spottiswoode, 1965, vol. 4, p. 2157. 6 (a) A. B. Sen and P. R. Singh, J. Indian Chem. Soc., 1960, 37, 217; (b) P. P. Joshi, T. R. Ingle and B. V. Bhide, J. Indian Chem. Soc., 1959, 36, 59. J. CHEM. RESEARCH (S), 1998 89

ISSN:0308-2342    

DOI:10.1039/a705517j

出版商:RSC    

年代:1998

数据来源: RSC