摘要:

Mendeleev Communications Electronic Version, Issue 3, 2002 1 Synthesis of 1-aryl(hetaryl)-1,2,3-triazoles with the use of ionic liquids Ilya V. Seregin, Lyudmila V. Batog and Nina N. Makhova* N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation. Fax: +7 095 135 5328; e-mail: mnn@mail.ioc.ac.ru 10.1070/MC2002v012n03ABEH001590 1-Phenyl(furazanyl)-1,2,3-triazoles can be synthesised by the 1,3-dipolar cycloaddition of phenylazide 1 or 4-amino-3-azidofurazan 2 to acetylenes (or to 1-morpholinyl-2-nitroethene for 2) in ionic liquids {1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) for 1 or 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]) for 2}.Ionic liquids are promising reaction media for organic synthesis, which can be repeatedly used for performing reactions in place of ordinary organic solvents.1 Ionic liquids were used in the Friedel–Crafts reaction,2 the dimerisation of alkenes,3 the alkylation of carbonyl compounds,4 the Heck reaction,5,6 and the Diels–Alder reaction.7 As a rule, these reactions were considerably accelerated in ionic liquids; therefore, the reactions can be carried out under milder conditions.The regioselectivity increases in the case of ambident substrates.8 In this context, the synthesis of heterocyclic compounds in ionic liquids seems to be promising. Only several works concerning this problem were published, in particular, the synthesis of oxazoline or imidazoline derivatives by the 1,3-dipolar cycloaddition of imidates, which were prepared from diethylaminomalonate, to 2-ethoxybenzaldehyde or imines as dipolarophiles,9(a),(b) the preparation of indoles9(c) and the synthesis of 3,4-dihydropyrimidine- 2(1H)-one.9(d) Recently, 3-(4-nitro-1,2,3-triazol-1-yl)-4-R-furazans and 3-[4(5)- alkyl- or 4,5-dialkyl-1,2,3-triazol-1-yl]-4-R-furazans 3 were synthesised in our laboratory by the 1,3-dipolar cycloaddition of azidofurazanes to 1-morpholinyl-2-nitroethylene10 and substituted acetylenes,11 respectively, in standard solvents.In a number of cases, the reaction with monosubstituted acetylenes occurred regioselectively. These bicyclic compounds potentiate the NOdependent activation of soluble guanylate cyclase; that is, they are nitrogen oxide donors.12 However, compounds 3 can be synthesised under severe conditions (120 h at 110 °C for 1-morpholinyl- 2-nitroethylene and 20–120 h at 65–80 °C for acetylene derivatives).We performed the above reactions in ionic liquids in order to develop a more efficient synthetic procedure for triazolylfurazans 3. At the first stage, we synthesised 4,5-bis(hydroxymethyl)- 1-phenyl-1,2,3-triazole 4 by the 1,3-dipolar cycloaddition of phenylazide 1 to butynediol 5a.According to published data,13 this reaction can be performed only at 120 °C for 12 h. The following ionic liquids based on 1-methylimidazole were chosen: butylmethylimidazolium hexafluorophosphate [bmim][PF6]14 and butylmethylimidazolium tetrafluoroborate [bmim][BF4]15 (Scheme 1). These ionic liquids are readily available and stable to air and moisture.The interaction of phenylazide 1 with butynediol 5a was studied in both of the ionic liquids at 80–120 °C. The use of [bmim][BF4] at 120 °C for 3 h was found to be optimum; the yield of compound 4 was comparable to the yield obtained in accordance with the known procedure† (Scheme 2; Table 1, entry 1).13 We found that the [bmim][PF6] ionic liquid can be used in this reaction at temperatures no higher than 90 °C; however, the test reaction does almost not occur at this temperature. An increase in the temperature results in the partial decomposition of the ionic liquid.Thus, using this model example, we found that ionic liquids that are stable in air at room temperature can serve as a reaction medium for the preparation of 1-substituted 1,2,3-triazoles by the 1,3-dipolar cycloaddition of azides to acetylene derivatives.This reaction occurred at a much higher rate than in standard organic solvents. Thus, we believed that the ionic liquids can also be successfully used for the synthesis of compounds 3. To evaluate the effect of ionic liquids, we examined the reaction between 3-azido-4-aminofurazan 2 and dipolarophiles (butynediol 5a, propargyl alcohol 5b, and 1-morpholinyl-2- nitroethylene 5c), which were previously entered into the reaction with azide 2, at 75–80 °C (Scheme 3).We found that under these conditions the reaction was considerably accelerated only in [bmim][PF6]. Table 1 summarises the reaction conditions. Data given in Table 1 indicate that azide 2 more rapidly reacted with acetylene derivatives 5a,b than in the case when published procedures were used.The yields of 4-amino-3-[4,5- bis(hydroxymethyl)-1,2,3-triazol-1-yl]furazan 3a and a mixture of 4-amino-3-(5-hydroxymethyl-1,2,3-triazol-1-yl)furazan 3b N N Me i N N Me Bu Cl ii or iii N N Me Bu X Scheme 1 Reagents and conditions: i, BuCl, toluene, reflux, 24 h; ii, (for X = PF6), HPF6, H2O, 20 °C, 12 h; iii, (for X = BF4), NH4BF4, acetone, 20 °C, 24 h.† All compounds were previously described; thus, they were characterised by a comparison of their melting points and spectroscopic data with published data. 1H NMR spectra were measured on Bruker WM-250 (250 MHz) and Bruker AM-300 (300 MHz) spectrometers. TLC monitoring was performed on Silufol UV 254 silica gel plates, the eluent was chloroform–acetone–methanol (10:2:1) or benzene–acetone (9:1).Melting points were determined on a Boetius PHMK 05 instrument. 4,5-Bis(hydroxymethyl)-1-phenyl-1,2,3-triazole 4. A mixture of 0.85 mmol of phenylazide 1, 0.80 mmol of a substituted acetylene and 1.5 mmol of [bmim]BF4 was stirred at 120 °C for 3 h. The reaction mixture was cooled to room temperature and extracted with ethyl acetate (3×10 ml).The solvent was evaporated, the residue was treated with a minimum volume of acetone, the precipitate was filtered off, washed with 10 ml of acetone and dried in air. PhN3 + HOCH2C CCH2OH i 1 5a N N N CH2OH HOH2C Ph 4 Scheme 2 Reagents and conditions: i, [bmim][BF4], 3 h, 120 °C. N O N N3 H2N 2 N O N H2N N N N R2 R1 O N CH CH NO2 R2 R1 5a,b 5c 3a–d a R1 = R2 = CH2OH b R1 = CH2OH, R2 = H c R1 = H, R2 = CH2OH d R1 = H, R2 = NO2 Scheme 3Mendeleev Communications Electronic Version, Issue 3, 2002 2 and 4-amino-3-(4-hydroxymethyl-1,2,3-triazol-1-yl)furazan 3c (entries 2,3)‡ were comparable or even higher.In the reaction with propargyl alcohol 5b, the 3b:3c ratio between isomers noticeably changed in favour of compound 3b; that is the use of the [bmim][PF6] ionic liquid as a reaction medium for the interaction of azidofurazan 2 with monosubstituted acetylene increased the regioselectivity of the reaction. The reaction with compound 5c was completed in 12 h at 70 rather than 110 °C.§ However, in this case, the yield of 4-amino-3-(4-nitro-1,2,3-triazol-1-yl)furazan 3d was lower than the published value.Evidently, morpholine, which was released in the course of reaction, reacted with the final product to decrease its yield. It is likely that the rate of this reaction in the ionic liquid also increased. The accumulation of by-products in the course of reaction was detected by TLC monitoring. The possibility of repeatedly using an ionic liquid was tested by the example of the synthesis of compound 3a, which was performed three times in the same portion of an ionic liquid with almost no decrease in the yield.Thus, we found that ionic liquids can be successfully used as reaction media for the synthesis of 1-aryl(hetaryl)-1,2,3-triazoles by the 1,3-dipolar cycloaddition of both aromatic and heterocyclic azides to substituted acetylenes and enamines.Both the rate and the regioselectivity of the reaction increased as compared to analogous reactions in standard organic solvents. These results form the basis for a promising new branch of the chemistry of heterocyclic compounds – the use of ionic liquids for performing heterocyclisation reactions. This study was supported by a complex scientific programme of the Russian Academy of Sciences (2001–2002).References 1 T. Welton, Chem. Rev., 1999, 99, 2071. 2 J. A. Boon, J. A. Levitsky, J. L. Pflug and J. S. Wilkes, J. Org. Chem., 1986, 51, 480. 3 S. M. P. Silva, A. Z. S. Suarez, R. F. De Souza and J. Dupont, Polym. Bull., 1998, 40, 401. 4 C. M. Gordon and A. McCluskey, Chem. Commun., 1999, 337. 5 A. J. Carmichael, M. J. Earle, J. D. Holbrey, P. B. McCormac and K.R. Seddon, Org. Lett., 1999, 1, 997. 6 V. P. W. Bohm and W. A. Hermann, Chem. Eur. J., 2000, 6, 1017. 7 T. Fischer, A. Shethi, T. Welton and J. Woolf, Tetrahedron Lett., 1999, 40, 793. 8 M. J. Earle, P. B. McCormac and K. R. Seddon, Chem. Commun., 1998, 2245. 9 (a) J. Fraga-Dubreuil and J. P. Bazureau, Tetrahedron Lett., 2000, 41, 7351; (b) J. Fraga-Dubreuil and J. P. Bazureau, Tetrahedron Lett., 2001, 42, 6097; (c) G.L. Rebeiro and B. M. Khadikar, Synthesis, 2001, 370; (d) J. Peng and Y. Deng, Tetrahedron Lett., 2001, 42, 5917. 10 L. V. Batog, V. Yu. Rozhkov, Yu. A. Strelenko, O. V. Lebedev and L. I. Khmel’nitskii, Khim. Geterotsikl. Soedin., 2000, 100 [Chem. Heterocycl. Compd. (Engl. Transl.), 2000, 36, 91]. 11 L. V. Batog, L. S. Konstantinova, V. Yu.Rozhkov, Yu. A. Strelenko, O. V. Lebedev and L. I. Khmel’nitskii, Khim. Geterotsikl. Soedin., 2000, 406 [Chem. Heterocycl. Compd. (Engl. Transl.), 2000, 36, 343]. 12 L. V. Batog, V. Yu. Rozhkov, Yu. V. Khropov, N. V. Pyatakova, O. G. Bousygina, I. S. Severina and N. N. Makhova, Russ. Pat. 2158265, 2000. 13 W. Winter and E. Muller, Chem. Ber., 1974, 107, 715. 14 D. W. Armstrong, L. He and Y.-S.Liu, Anal. Chem., 1999, 71, 3873. 15 P. A. Suarez, J. E. L. Dullius, S. Einloft, R. F. de Souza and J. Dupont, Polyhedron, 1996, 15, 1217. ‡ 4-Amino-3-(4-R2-5-R1-1,2,3-triazol-1-yl)furazans 3a–c (general procedure). A mixture of 1 mmol of 4-amino-3-azidofurazan 2, 1.25 mmol of a substituted acetylene and 2 mmol of [bmim]PF6 was stirred at 75–80 °C for 3.5 to 7.5 h.The reaction mixture was cooled to room temperature and treated with a minimum volume of acetone, the precipitate was filtered off and washed with 10 ml of acetone. The solvent was evaporated and the residue was treated with 10 ml of acetone, the new precipitate was filtered off and washed with 5 ml of acetone. The last operation was repeated once more. Combined portions of the precipitate were dried in air.The ionic liquid can be easily recovered and reused after the evaporation of acetone. The ratio between compounds 3b and 3c in the mixture was calculated from 1H NMR-spectroscopic data according to the integral intensities of corresponding proton signals in [2H6]DMSO: 3b, 4.67 (d, 2H, 5'-CH2), 5.44 (t, 1H, OH), 8.65 (s, 1H, 4'-CH); 3c, 4.80 (d, 2H, 4'-CH2), 5.69 (t, 1H, OH), 7.96 (s, 1H, 5'-CH).§ 4-Amino-3-(4-nitro-1,2,3-triazol-1-yl)furazan 3d. A mixture of 8 mmol of 4-amino-3-azidofurazan 2 and 7 mmol of 1-morpholinyl-2-nitroethene was added to 8 mmol of [bmim]PF6 and stirred at 70 °C for 12 h. The reaction mixture was cooled to room temperature and extracted with diethyl ether (3×20 ml). The solvent was evaporated under reduced pressure and the product was isolated by column liquid chromatography. The isolation of triazole 3d was performed by column liquid chromatography using SiO2 (40:100) as a stationary phase and a mixture of benzene and ethyl acetate (13:5) as an eluent. Table 1 Reagents, conditions and results of the synthesis of 1,2,3-triazoles in ionic liquids. Entry Azide Dipolarophile Ionic liquids and conditions 1,2,3- triazoles (yields) Conditions and yields according to published data 1 1 5a [bmim]BF4, 120 °C, 3 h 4 (65%) Benzene, 120 °C, 12 h (73%)13 2 2 5a [bmim]PF6, 80 °C, 7.5 h 3a (75%) EtOH, reflux, 30 h (57%)11 3 2 5b [bmim]PF6, 80 °C, 6.5 h 3b:3c, 4.5:1 (71%) EtOH, reflux, 45 h, 3b:3c, 2.5:1 (79%)11 4 2 5c [bmim]PF6, 70 °C, 12 h 3d (35%) Toluene, reflux, 120 h (80%)10 Received: 10th April 2002; Com. 02/1916

ISSN:0959-9436     

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 3, 2002 1 3-Hydroxy-2,2-dimethylimidazolidin-4-one: the regioselective synthesis and chiral crystallization Igor V. Vystorop,*a Konstantin A. Lyssenkob and Remir G. Kostyanovskyc a Institute of Problems of Chemical Physics, Russian Academy of Sciences, 142432 Chernogolovka, Moscow Region, Russian Federation. Fax: +7 096 515 3588; e-mail: vystorop@icp.ac.ru b A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russian Federation. Fax: +7 095 135 5085; e-mail: kostya@xray.ineos.ac.ru c N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russian Federation. Fax: +7 095 938 2156; e-mail: kost@center.chph.ras.ru 10.1070/MC2002v012n03ABEH001603 The condensation of glycine hydroxamic acid with acetone regioselectively leads to the formation of the title achiral cyclic hydroxamic acid, which crystallises from an acetone solution as chiral crystals (space group P212121) of (P,1R,3S) and (M,1S,3R) enantiomers.Alkylation and acylation of unsubstituted hydroxamic acids (HA) mainly lead to their (N)-O derivatives.1 For example, the reaction of ¥á-amino HA with aldehydes affords cyclic O-alkyl hydroxamates 1 or corresponding acyclic azomethins.2 Nevertheless, it was found previously3 that the condensation of DL-¥á-alanine hydroxamic acid (¥á-AlaHA) with acetone proceeds as the regioselective N-alkylation of the hydroxamic group to provide cyclic HA 2 in 83% yield.This finding is in agreement with the reactions of ¥â-AlaHA with aliphatic aldehydes or ketones solely giving products 3.4 In this work, we report that the condensation of glycine HA (GlyHA 4) with acetone proceeds similarly3 to afford cyclic HA 5 (Scheme 1).The structure of product 5 was found by X-ray diffraction analysis¢Ó and confirmed by spectroscopic data¢Ô and the test reaction with FeCl3. According to 1H and 13C NMR spectra,¢Ô neither the ring.chain tautomerism nor the hydroxyamide.hydroxynitrone tautomerism (O=C.N.OH HO.C=N¢çO) of the chelate type, which are slow and fast,5(a) on an NMR time scale, respectively, have been observed for 5 in solution. The absence of the hydroxyamide .hydroxynitrone tautomerism follows from the comparison of the chemical shifts of carbonyl carbons for 5 (d 171.8 ppm)¢Ô and 3-methoxy-1,2,2,5,5-pentamethylimidazolidin-4-one 6 (d 171.1 ppm, in MeOH),5(b) bearing in mind that 6 has no ability for such a kind of tautomerism.The significant upfield shift of the methoxyimine carbon signal (d 156.7 ppm, in MeOH) of a methoxynitrone derivative of 6 (MeO.C=N¢çO)5(b) supports this conclusion. The characteristic feature of the molecular structure of 5 in a crystal (Figure 1) is the non-planarity of the hydroxamic fragment O=C.N.O (jexo = 19.3¡Æ), which is caused probably by the minimization of the dipole.dipole repulsion of its cisoriented dipoles and torsion strain of exocyclic C=O and N.O bonds.The synperiplanar (sp) twist of a hydroxamic fragment specifies the spiral chirality as P (plus, jexo > 0) (Figure 1) or M (minus, jexo < 0),6 depending on the heterocycle conformation chirality (vide infra) of the molecule of 5, and it is inconsistent with the general point of view1 concerning the planarity of a hydroxamic fragment in HAs.Thus, in the molecule of 5, the displacements of O(1), N(1) and C(2) atoms from the mean plane N(3)C(4)C(5)O(2) (to within ¡¾0.0005 A) are equal to 0.396, .0.126 and 0.348 A, respectively.An opposite sence of twist of exo- (jexo) and endocyclic (t0) dihedral angles at the central N(3).C(4) amide bond, as well as the presence of the electronegative O(1) substituent adjacent to the N(3) atom, promote7 the weakening of the nN.¥�*(C=O) amide resonance and an increase in the sp3 character and pyramidalization of the amide N(3) atom [¥Òw N(3) = 350.8¡Æ; the height of the pyramid is equal to 0.25 A].Correspondingly, a lengthening of the N(3).C(4) bond and a shortening of the C(4)=O(2) bond are observed in 5 (Figure 1) as compared with the average lenghts of the corresponding bonds [N.C(O), HN O NH H R1 O H R2 N N H Me Me OH O Me H HN N O R2 R1 OH 1 R1, R2 = Alk, Ar 3 R1, R2 = H, Alk (¡¾)-2 Scheme 1 Reagents and conditions: i, suspension of 450 mg (5 mmol) of GlyHA, acetone (2 equiv.) and 50 cm3 of MeOH, reflux, 3 h, then filtration, evaporation, and recrystallization from acetone.NH2CH2 C NHOH O Me2C O 4 N N OH Me Me H H H O 5 t1 t2 t3 t0 t4 jexo i ¢Ó Crystallographic data for 5 at 120 K: crystals of C5H10N2O2 are orthorhombic, space group P212121, a = 7.1099(9), b = 9.4282(11) and c = 9.7646(10) A, V = 654.56(13) A3, Z = 4, M= 130.15, dcalc = 1.321 g cm.3, m(MoK¥á) = 0.103mm.1, F(000) = 280.Intensities of 2438 reflections were measured with a Smart 1000 CCD diffractometer at 120 K [l(MoKa) = = 0.71073 A, w-scans with a 0.3¡Æ step in w and 10 s per frame exposure, q < 27¡Æ], and 1297 independent reflections (Rint = 0.0299) were used in further refinement. The structure was solved by a direct method and refined by the full-matrix least-squares technique against F2 in the anisotropic.isotropic approximation. Hydrogen atoms were located from the Fourier synthesis and refined in the isotropic approximation. The refinement converged to wR2 = 0.1412 and GOF = 0.973 for all independent reflections [R1 = 0.0532 was calculated against F for 1040 observed reflections with I > 2s(I)].The number of the refined parameters was 122. All calculations were performed using SHELXTL PLUS 5.0 on IBM PC AT. Atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details, see ¡®Notice to Authors¡�, Mendeleev Commun., Issue 1, 2002.Any request to the CCDC for data should quote the full literature citation and the reference number 1135/109. ¢Ô Characteristics and spectroscopic data. IR spectra were obtained on a Specord-82M spectrometer. NMR spectra were recorded on a Bruker WM-400 NMR spectrometer (with TMS as an internal standard) at 400.13 (1H) and 100.62 MHz (13C). Compound 4 (GlyHA) was prepared as described previously.17 5: yield 57%, mp 177.178 ¡ÆC (decomp.). 1H NMR (CD3OD) d: 1.37 (s, 6H, 2Me), 3.37 (s, 2H, CH2). 1H NMR ([2H6]DMSO) d: 1.19 (s, 6H, 2Me), 3.12 (br. s, 1H, NH), 3.14 (s, 2H, CH2), 9.39 (br. s, 1H, OH). 13C NMR (CD3OD) d: 24.24 (qq, Me, 1J 127.4 Hz, 3J 3.1 Hz), 45.88 (tr, CH2, 1J 143.8 Hz), 78.80 (m, NCN), 171.80 (tr, C=O, 2J 5.0 Hz). IR (KBr, n/cm.1): 3214 (NH), 2982, 2928 (Me, CH2), 2719 (br.), 2631 (br.), 2538 (br., OH), 1697 (C=O), 1514, 1472, 1464, 1389, 1368, 1308, 1256, 1180, 1170, 1112, 1081, 1040, 1001, 968, 945 sh, 933, 900, 838, 705, 610, 579, 532, 412.Mendeleev Communications Electronic Version, Issue 3, 2002 2 1.335(1) A; C=O, 1.232(1) A]8(a) of ¥ã-lactams in a crystalline state. According to the quantitative evaluation of the heterocyclic ring form of 5 in a crystal (Figure 1) based on the pseudorotation parameters such as phase angle (P) and amplitude of puckering (tm),9 the chiral N-type (t2 > 0) conformation of the heterocyclic ring of 5 (PN = 44.4¡Æ, tm = 31.4¡Æ) is intermediate between the forms of ideal half-chair N(1) C(2)T (PN = 36¡Æ, t0 = t1, t2 = t4, t3 = tmax) and envelope C(2)E (PN = 54¡Æ, |t0| = t2, |t3| = = t4, t1 = 0), the latter form being typical of imidazolidines.10 The phase angles PS for corresponding enantiomeric forms N(1) C(2)T and C(2)E of S-type (t2 < 0) heterocycle will be equal to 216¡Æ and 234¡Æ (Scheme 2), respectively.The pyramidality of the amine N(1) atom [¥Òw N(1) = 317.2¡Æ] is enhanced by its inclusion into a heterocyclic ring and by a compression of the endocyclic C(2)N(1)C(5) bond angle.This corresponds to an increase in the p-character of hybrid orbitals of the N(1) in ¡®internal¡� N(1).C(2) and N(1).C(5) bonds, leading to an elongation of these bonds (Figure 1) in comparison with the averaged X-ray diffraction value (1.469 A)8(b) for the (C)2.Nsp3 bond. The pseudo-e orientation of the N(1) lone pair (LP) assists the nN(1).¥ò*C(2).N(3) interaction (anomeric effect7) caused by the antiperiplanar (ap) orientation of this LP to the C(2).N(3) bond [j LPN(1)N(1)C(2)N(3) = .152.5¡Æ].Together with the concerted nO(1).¥ò*N(3).C(2) interaction [j LPO(1)O(1)N(3)C(2) = .145¡Æ], this results in an appreciable weakening of the C(2).N(3) bond in 5 (Figure 1) as compared to the mean X-ray diffraction length [1.455(1) A]8(a) of the N.C¥â bond in ¥ã-lactams. Moreover, the pseudo-e LPN(1) has the ap-orientation to LPN(3) [pseudo-dihedral angle j LPN(1)N(1)N(3)LPN(3) = 154¡Æ, and the bond angle between these LP vectors is equal to 122¡Æ], which promotes the decreasing of their dipole.dipole repulsion (cf.mD for 5a and 5b, vide infra) and corresponds to a preferable mutual orientation of the LPs of the NCN geminal system.11 The heterocycle conformation of 5 in a crystal is also stabilised by ap-orientation as of N(1).C(2) and N(3).O(1) polar bonds [j N(1)C(2)N(3)O(1) = 175.2(2)¡Æ], and also of N(1).C(5) and C(4)=O(2) bonds [j N(1)C(5)C(4)O(2) = 174.9(2)¡Æ], which assist the diminution of their dipole.dipole repulsion and torsion strain.The enhancement of the directivity of pseudo-e oriented LPN(1) increases the proton-accepting ability of the N(1) atom and aids to the forming of the strong O(1).H(1O)¡�¡�¡�N(1) intermolecular H-bond of the zwitterionic type.Another type of intermolecular H-bonding observed in the crystal of 5 is a weak12 H-bond of the N(1).H(1)¡�¡�¡�O(2)=C(4) type (Figure 2). The comparison of homologues 2 and 5 demonstrates that their molecular structures in a crystalline state are conformationally similar [cf.PN = 39.5¡Æ, tm = 35.5¡Æ, ¥Òw N(3) = 351.2¡Æ for 2].3 Nevertheless, their crystal structures formed by the same types of intermolecular H-bonds are essentially distinct from each other. Thus, configurationally rigid racemate 2 crystallises from an acetone solution as heterochiral crystals (space group P21/c, Z = 8, mp 163.164 ¡ÆC),3 whereas non-rigid (formally achiral) HA 5 gives chiral crystals (space group P212121, Z = 4, mp 177.178 ¡ÆC)¢Ó from this solvent.According to the geometry and energy of 5 optimization by the DFT method (Becke3LYP/6-31G*),¡× the dominant conformer 5a [for (P,1R,3S) enantiomer] is stabilised in an isolated state in a quite ideal C(2)E envelope form of the heterocyclic ring (PN = 53.8¡Æ, tm = 32.8¡Æ) with the retention of a noticeable twist Scheme 2 Degenerate racemization of 5 as illustrated by ideal molecular shapes.C N N O H Me OH H H Me N N HO Me Me Ha H H O 1 2 3 4 5 N N HO He H H O Me Me (P,1R,3S)-5c C(2)T, PN = 36¡Æ N(1) (P,1R,3S)-5a C(2)E, PN = 54¡Æ (M,1R,3R)-5b' C(2)E, PS = 234¡Æ N(1)inv N(1)inv N N HO Me Me He H H O N N HO Ha H H O Me Me (P,1S,3S)-5b C(2)E, PN = 54¡Æ (M,1S,3R)-5a' C(2)E, PS = 234¡Æ C N N O H Me OH H H Me (M,1S,3R)-5c' C(2)T, PS = 216¡Æ N(1) Rint Rint ¡× The geometries of cyclic hydroxamic acid (P,1R,3S)-5a and its diastereomer (P,1S,3S)-5b were completely optimised at the density functional theoretical level (DFT) with the conventional 6-31G* basis set using procedures implemented in the Gaussian 98 system of programs.18 For the DFT calculations, a hybrid approach based on Becke¡�s three parameter functional19 was employed (Becke3LYP). As the convergence criteria the default threshold limits of 0.00045 and 0.0018 a.u.were applied for the maximum force and displacement, respectively. The calculated energies (in hartrees) and dipole moments (in debyes) are: .456.45047 and 2.54 (5a), .456.44352 and 3.35 (5b), respectively.We are grateful to Professor Yu. N. Bubnov (Institute of Organoelement Compounds, Russian Academy of Sciences) for his help in carrying out the quantum-chemical calculations. H(71) H(72) H(73) C(7) H(1O) O(1) O(2) N(3) C(4) C(2) N(1) H(1N) H(52) C(5) H(51) H(62) H(63) H(61) C(6) Figure 1 Molecular structure of hydroxamic acid 5.[The absolute configuration is not known, and our assignment as (P,1R,3S) is only illustrative]. Selected bond lengths (A): O(1).N(3) 1.394(3), N(1).C(2) 1.475(3), N(1).C(5) 1.489(4), O(2).C(4) 1.225(3), C(2).N(3) 1.484(3), C(2).C(6) 1.523(4), C(2).C(7) 1.523(4), N(3).C(4) 1.343(3), C(4).C(5) 1.512(4); selected bond and dihedral angles (¡Æ): C(2).N(1).C(5) 106.1(2), N(1).C(2).N(3) 100.4(2), N(1).C(2).C(6) 112.1(2), N(1).C(2).C(7) 110.8(2), N(3).C(2).C(6) 109.9(2), N(3).C(2).C(7) 111.4(2), C(6).C(2).C(7) 111.8(2), O(1).N(3).C(2) 117.7(2), O(1).N(3).C(4) 119.7(2), C(2). N(3).C(4) 113.4(2), O(2).C(4).N(3) 127.1(2), O(2).C(4).C(5) 127.4(2), N(3).C(4).C(5) 105.6(2), N(1).C(5).C(4) 105.3(2); H(1O).O(1).N(3). C(2) 95, H(1O).O(1).N(3).C(4) .120, H(1N).N(1).C(2).N(3) 82.3, C(5).N(1).C(2).N(3) (t3) .29.3(2), C(5).N(1).C(2).C(6) 87.2(3), C(5).N(1).C(2).C(7) .147.1(2), H(1N).N(1).C(5).H(51) 153.4, H(1N).N(1). C(5).H(52) 29.3, C(2).N(1).C(5).C(4) (t2) 22.4(3), N(1).C(2).N(3). C(4) (t4) 28.4(3), C(6).C(2).N(3).O(1) 57.0(3), C(6).C(2).N(3).C(4) .89.8(3), C(7).C(2).N(3).O(1) .67.5(3), C(7).C(2).N(3).C(4) 145.7(2), O(1).N(3).C(4).O(2) (jexo) 19.3(4), O(1).N(3).C(4).C(5) .160.9(2), C(2).N(3).C(4).O(2) 165.3(2), C(2).N(3).C(4).C(5) (t0) .14.9(3), N(3).C(4).C(5).N(1) (t1) .5.0(3).Mendeleev Communications Electronic Version, Issue 3, 2002 3 of the hydroxamic fragment of the same spirality sence (P, jexo = 16.1¡Æ), a slight pyramidality of amide N(3) nitrogen [¥Òw N(3) = 346.6¡Æ], and the pseudo-e orientation of LPN(1) [j H(1N)N(1)C(2)N(3) = 86.5¡Æ] of the pyramidal N(1) atom [¥Òw N(1) = 322.9¡Æ] with (R)-configuration. However, its N(1) epimer [(P,1S,3S) diastereomer 5b, Scheme 2] with the pseudo-a orientation of LPN(1) [j H(1N)N(1)C(2)N(3) = .152.9¡Æ], having the same handedness (N-type, t2 = 22.2¡Æ) of heterocycle conformation, exhibits the structure [PN = 45.5¡Æ, tm = 31.7¡Æ, jexo = = 22.1¡Æ, ¥Òw N(3) = 349.3¡Æ, ¥Òw N(1) = 331.1¡Æ] almost identical to 5 in a crystal, but it is populated by less than 0.1% relatively to 5a [relative energy ..E0 (5a,b) = 4.36 kcal mol.1].¡× Steric and stereoelectronic factors, stabilising as the heterocycle conformation in form close to C(2)E [or C(2)E] envelope and pseudo-e orientation of LPN(1) of molecule 5 in crystal (vide supra) and free (5a) states are probably the same.However, a weak intramolecular H-bond of the O.H¡�¡�¡�O=C type [d H(1O)¡�¡�¡�O(2) = 2.08 A, j1 H(1O)O(1)N(3)C(4) = .6.4¡Æ] exists in 5a, whereas it is absent from the crystalline state [d H(1O)¡�¡�¡�O(2) = 3.42 A, j1 = .120¡Æ] (Figure 1) and the molecule of 5b [d H(1O)¡�¡�¡�O(2) = 2.98 A, j1 = .88.6¡Æ]. The absence of this H-bond is sterically favourable for a decrease in the mutual repulsion of LPN(3) and LP[O(1)] {j LPN(3) N(3)O(1)LP1 O(1) [LP2 O(1)] = .132¡Æ and 108¡Æ in the crystal of 5}.Thus, compound 5 is conformationally and tautomerically homogeneous in both a crystal and solution, existing as (P,1R,3S) and (M,1S,3R) enantiomers, for which degenerate racemization probably consists of two relatively independent diastereomeric steps of stereomutation (Scheme 2): (a) the interconversion of chiral conformation of heterocycle (from N to S type and vice versa) by a pseudorotational or ¡®through the plane¡� mechanism,9(a) which is accompanied by the conamide nitrogen N(3) and the reversion of a helix chirality (P or M) of the hydroxamic fragment and (b) the configuration inversion of the amine N(1) atom by its pyramid inversion or proton transfer.The low energy of activation of the rate-limiting epimerization (either a or b) of sterically unhindered racemization of 5 did not allow us to observe (in solution) the chemical shift nonequivalence of signals from the geminal prochiral methyl groups or methylene group protons in the NMR spectra¢Ô at ambient temperature and the optical activity of the enantiomeric form of 5.The generation of chiral crystals by the crystallization of configurationally flexible compound 5 proceeds by such a way that the frozen chiral conformations of only one handedness are self-assembled in each single crystal, inducing crystal chirality.Enantiomorphous crystals consist of infinite helixes formed by strong (O.H¡�¡�¡�N type) and weak (N.H¡�¡�¡�O=C type) H-bonds along the crystallographic axes c and b, respectively (Figure 2), leading to the generation of a spatial H-bonded network. In conclusion, note that chiral crystals obtained from achiral compounds13 are substrates for absolute asymmetric synthesis14 and new chiral materials for non-linear optics.15 Moreover, their generation in the absence of any external chiral agent is interesting both for chiral crystal engineering and for solving the question of the origin of optical activity in nature.16 This work was supported by the Russian Foundation for Basic Research (grant nos. 00-03-32738 and 00-03-81187 BEL) and INTAS (grant no. 99-0157).References 1 L. Bauer and O. Exner, Angew. Chem., Int. Ed. Engl., 1974, 13, 376. 2 J. Charbonnel and J. Barrans, Compt. Rend., 1966, 263C, 824. 3 I. V. Vystorop, Z. G. Aliev, N. Yu. Andreeva, L. O. Atovmyan and B. S. Fedorov, Izv. Akad. Nauk, Ser. Khim., 2000, 180 (Russ. Chem. Bull., 2000, 49, 182). 4 O. A. Luk¡�yanov and P. B. Gordeev, Izv. Akad. Nauk, Ser. Khim., 1998, 691 (Russ.Chem. Bull., 1998, 47, 669). 5 (a) I. A. Grigor¡�ev, S. M. Bakunova and I. A. Kirilyuk, Izv. Akad. Nauk, Ser. Khim., 2000, 2066 (Russ. Chem. Bull., 2000, 49, 2031); (b) G. I. Shchukin, I. A. Grigor¡�ev and L. B. Volodarsky, Khim. Geterotsikl. Soedin., 1990, 478 [Chem. Heterocycl. Compd. (Engl. Transl.), 1991, 26, 409]. 6 R. S. Chan, C. K. Ingold and V. Prelog, Angew. Chem., Int.Ed. Engl., 1966, 5, 583. 7 S. A. Glover and A. Rauk, J. Org. Chem., 1999, 64, 2340. 8 (a) L. Norskov-Lauritsen, H.-B. Burgi, P. Hofmann and H. R. Schmidt, Helv. Chim. Acta, 1985, 68, 76; (b) F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, G. Orpen and R. Taylor, J. Chem. Soc., Perkin Trans. 2, 1987 (12), Suppl. 1. 9 (a) C. Altona and M. Sundaralingam, J. Am. Chem. Soc., 1972, 94, 8205.; (b) I.V. Vystorop, A. Rauk, C. Jaime, I. Dinares and R. G. Kostyanovsky, Khim. Geterotsikl. Soedin., 1995, 1479 [Chem. Heterocycl. Compd. (Engl. Transl.), 1995, 31, 1280]. 10 A. Skancke and L. Vilkov, Acta Chem. Scand., 1988, 42A, 717. 11 (a) R. A. Y. Jones, A. R. Katritzky and M. Snarey, J. Chem. Soc. (B), 1970, 131, 135; (b) F. G. Riddell, The Conformational Analysis of Heterocyclic Compounds, Academic Press, London, 1980. 12 R. Taylor and O. Kennard, Acc. Chem. Res., 1984, 17, 320. 13 J. Jasques, A. Collet and S. H. Wilen, Enantiomers, Racemates, and Resolutions, Wiley, New York, 1981, pp. 14.23. 14 (a) B. S. Green, M. Lahav and D. Rabinovich, Acc. Chem. Res., 1979, 12, 191; (b) M. Sakamoto, Chem. Eur. J., 1997, 3, 684. 15 G. Heppke and D.Moro, Science, 1998, 279, 1872. 16 W. A. Bonner, Top. Stereochem., 1988, 18, 1. 17 K. G. Cunningham, G. T. Newbold, F. S. Spring and J. Stark, J. Chem. Soc., 1949, 2091. 18 M. J. Frisch, G.W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A.Montgomery, Jr., R. E. Stratmann, J. C. Burant, S. Dapprich, J. M. Millam, A. D. Daniels, K. N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K.Morokuma, D. K.Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V. Ortiz, A. G. Baboul, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, J. L. Andres, C. Gonzalez, M. Head-Gordon, E. S. Replogle and J. A. Pople, Gaussian 98, Revision A.7, Gaussian, Inc., Pittsburgh PA, 1998. 19 (a) A. D. Becke, J. Chem. Phys., 1993, 98, 5648; (b) A. D. Becke, Phys. Rev. A., 1988, 38, 3098; (c) C. Lee, W. Yang and R. G. Parr, Phys. Rev. B., 1988, 37, 785. H(1O') O(2') H(1N) N(1) O(1) O(2) H(1O) N(1') Figure 2 Hydrogen-bonded helixes in the crystal structure of 5 (perspective view on the bc plane). Hydrogen bonds are shown by dashed lines. The geometric parameters of H-bonds are as follows: H(1O)¡�¡�¡�N(1) 1.599 A, O(1)¡�¡�¡�N(1) 2.679 A, O(1).H(1O)¡�¡�¡�N(1) 167.9¡Æ; H(1N)¡�¡�¡�O(2) 2.155 A, N(1)¡�¡�¡�O(2) 3.041 A, N(1).H(1N)¡�¡�¡�O(2) 174.4¡Æ. [The symmetry transformations used to generate the atoms N(1) (.x . 1/2, .y + 1, z + 1/2) and O(2) (.x, y . 1/

ISSN:0959-9436     

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 3, 2002 1 Novel selective acid-catalysed rearrangement of the carane-type ¥á-(N-acylamino)oximes: the X-ray structure of (1S,5S)-1-isopropyl- 3,5-dimethyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-6-one (E)-oxime Alexander M. Agafontsev,a Tatyana V. Rybalova,b Yury V. Gatilovb and Alexey V. Tkachev*b a Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russian Federation b N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russian Federation. Fax: +7 3832 344 752; e-mail: atkachev@nioch.nsc.ru 10.1070/MC2002v012n03ABEH001607 The acid-catalysed rearrangement of carane-type ¥á-(N-acylamino)oximes results in the formation of new bridged heterocycles with the 3-substituted 1-isopropyl-6-hydroxyimino-3-methyl-2-oxa-4-azabicyclo[3.3.1]non-3-ene skeleton.(+)-3-Carene and its oxygen-, nitrogen- and sulfur-containing derivatives represent one of the most important groups of monoterpenoids. Under acidic conditions, the derivatives of 3-carene are usually transformed to compounds of the p-menthane series and sometimes form the derivatives of m-menthane and eucarvone.Most of the reactions give complex mixtures of isomers and great amounts of tar-like products.1 We describe here a new unusual stereoselective cyclization of 3-carene derivatives to bicyclic bridged heterocycles of the 2-oxa-4-azabicyclo- [3.3.1]non-3-ene series. When dissolved in a concentrated sulfuric acid, ¥á-amino oximes 1 derived from (+)-3-carene undergo isomerization to afford p-menthane derivatives 2 (Scheme 1).2 We found that N-acyl derivatives 3 of the same structural type are transformed to m-menthane derivatives 4 in good yields under the action of sulfuric acid in chloroform (Scheme 2).The reaction proceeds smoothly in the case of N-acetyl derivative 3a to give compound 4a,¢Ó as well as in the case of derivatives of benzoic (3b ¢ç 4b),¢Ô 2-thiophencarboxylic (3c ¢ç 4c)¡× and 1-adamantane carboxylic (3d ¢ç 4d)¢Ò acids.Analysis of high-field 2D 1H.1H and 13C.1H-correlation NMR spectra of new compounds 4a.d showed similarity of the NMR parameters (proton and carbon chemical shifts and 1H.1H and 13C.1H spin.spin couplings) for the bicyclic system and thus proved compounds 4a.b to belong to the same structural type.Configuration of the simplest N-acetyl derivative 4a was solved by X-ray crystallography (Figure 1).¢Ó¢Ó The formation of compounds 4a.d can be described by Scheme 3, which provides for addition of a proton and cyclopropane ring cleavage to form m-menthane-type cation 5 followed by participation of the carbonyl oxygen (structure 6) and the formation of immonium cation 7 whose deprotonation results in the final product 4.NR2 N OH 1 R = H, Alk NR2 N OH 2 i, H2SO4 (96%), 0 to 40 ¡ÆC ii, NH3.H2O 42% Scheme 1 N N OH 3a.d a R = Me b R = Ph c R = d R = N OH 4a.d i, H2SO4 (96%), r.t. ii, NH3.H2O 65.83% Scheme 2 H O R N O R 1 5 3 14 13 7 9 10 11 12 S ¢Ó Concentrated H2SO4 (2.5 ml, 96%, 50 mmol) was added dropwise to a stirred solution of N-acylated amine 4a (438 mg, 1.92 mmol) in CHCl3 (15 ml) at room temperature.The mixture was vigorously stirred for 3 h and then adjusted to pH 10.11 by the addition of concentrated aqueous ammonia (ice-cold bath). The organic phase was separated and the aqueous solution was extracted with tert-BuOMe (2¡¿10 ml). The combined organic extract was dried over MgSO4, filtered and concentrated at a reduced pressure to give a yellowish glass-like solid (400 mg), which was crystallised from acetonitrile to give pure (1S,5S)-1-isopropyl-3,5- dimethyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-6-one (E)-oxime (4a, 312 mg, 71% yield) as white crystals with mp 216.220 ¡ÆC (MeCN) and [a]20 578 +429 (c 0.83, CHCl3). 1H NMR (500 MHz, 10 mg cm.3 in CDCl3) d: 9.80 (s, 1H, N=OH), 3.27 (ddd, 7-H¥â, J 15.5, 6.2, 0.8 Hz), 1.98 (s, 3H, 13-Me), 1.94 (ddd, 8-H¥á, J 13.4, 3.2, 0.8 Hz), 1.82 (ddd, 7-H¥á, J 15.5, 13.1, 6.6 Hz), 1.75 (qq, 10-H, J 6.8, 6.8 Hz), 1.74 (d, 9-H¥â, J 13.2 Hz), 1.59 (ddd, 8-H¥â, J 13.4, 13.1, 6.6 Hz), 1.51 (dd, H¥á, J 13.2, 3.2 Hz), 1.39 (s, 3H, 14-Me), 0.91 (d, 3H, 11-Me, J 6.8 Hz), 0.89 (d, 3H, 12-Me, J 6.8 Hz). 13C NMR (125 MHz, 10 mg cm.3 in CDCl3) d: 160.64 (C-6), 160.04 (C-3), 79.56 (C-1), 54.31 (C-5), 37.59 (C-9), 36.38 (C-10), 33.18 (C-8), 24.91 (C-14), 21.32 (C-13), 17.02 (C-7), 16.61 (C-12), 16.42 (C-11). IR (CHCl3, nmax/cm.1): 3590 (O.H), 1650 (C=N), 895 (N.O). MS, m/z (%): 224.15149 (15, M+, calc. for C12H20N2O2: 224.16149), 165 (88), 159 (18), 148 (17), 123 (17), 107 (10), 82 (11), 60 (11), 55 (10), 43 (100), 42 (30), 41 (28), 28 (11). ¢Ô (1S,5S)-1-Isopropyl-5-methyl-3-phenyl-2-oxa-4-azabicyclo[3.3.1]non- 3-en-6-one (E)-oxime 4b: yield 83%, white crystals, mp 177.180 ¡ÆC (MeCN), [a]20 578 +193 (c 0.38, CHCl3).¡× (1S,5S)-1-Isopropyl-5-methyl-3-(thiophen-2-yl)-2-oxa-4-azabicyclo- [3.3.1]non-3-en-6-one (E)-oxime 4c: yield 78%, white crystals, mp 164 ¡ÆC (decomp., MeCN), [a]20 578 +92 (c 0.087, CHCl3).¢Ò (1S,5S)-3-(Adamantan-1-yl)-1-isopropyl-5-methyl-2-oxa-4-azabicyclo- [3.3.1]non-3-en-6-one (E)-oxime 4d: yield 65%, white crystals, mp 230. 233 ¡ÆC (MeCN), [a]20 578 +136 (c 0.62, CHCl3). ¢Ó¢ÓA Syntex P21 diffractometer with graphite-monochromated CuK¥á radiation was used to measure the unit cell parameters and to collect data (q-2q scans, q < 140¡Æ).Crystallographic data for compound 4a: C12H20N2O2, M = 224.30, crystal class orthorhombic, space group P212121, a = 7.050(1), b = = 10.671(2), c = 16.655(3) A, V = 1253.0(4) A3, Z = 4, dcalc = 1.189 g cm.3, m = 0.653mm.1, l = 1.54178 A, crystal size 0.4¡¿0.6¡¿1.2 mm. Absorption corrections were applied by an empirical method based on psi-scans (transmission 0.806.1.000).The structure was solved by direct methods and refined by a full matrix least-squares anisotropic.isotropic (for H atoms) procedure using the SHELXL97 program. The hydrogen atom positions were located from a difference Fourier map. The final indexes are wR2 = 0.1009, S = 1.079 for all 1378 F2 and R1 = 0.0352 for 1345 F0 > 4s(F0). The absolute structure parameter (Flack parameter) is equal to .0.2(4).Atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details, see ¡®Notice to Authors¡�, Mendeleev Commun., Issue 1, 2002. Any request to the CCDC for data should quote the full literature citation and the reference number 1135/108.Mendeleev Communications Electronic Version, Issue 3, 2002 2 Compounds 4a–d are white crystalline solids, which are insoluble in water and hydrocarbons, sparingly soluble in chloroform and methylene chloride, and readily soluble in methanol and dimethylsulfoxide. In spite of the presence of the imino ester group, compounds 4a–d are stable in air and are not prone to hydrolysis.We are grateful to the Russian Foundation for Basic Research (project no. 99-07-04729) for the opportunity to use the Cambridge Structural Database System and to the Ministry of Education of the Russian Federation for financial support of this work (Programme ‘Universities of Russia’, grant no. UR.05.01.036). References 1 (a) W. F. Erman, Chemistry of the Monoterpenes. An Encyclopedic Handbook, in Studies in Organic Chemistry, ed.P. G. Gassman, Marcel Dekker Inc., New York–Basel, 1985, vol. 11, part A, pp. 197–213; (b) W. F. Erman, Chemistry of the Monoterpenes. An Encyclopedic Handbook, in Studies in Organic Chemistry, ed. P. G. Gassman, Marcel Dekker Inc., New York–Basel, 1985, vol. 11, part B, pp. 861–928. 2 P. A. Petukhov and A. V. Tkachev, Tetrahedron, 1997, 53, 2535. Figure 1 Molecular structure of crystalline compound 4a. Seleed bond lengths (Å): C(5)–N(4) 1.476(3), N(4)=C(3) 1.269(3), C(3)–O(2) 1.353(2), C(1)–O(2) 1.469(2), C(6)–N(6) 1.266(2), O(6)–N(6) 1.400(2). The sofa-like conformation of the dihydrooxazine ring is characterised with the planar within ±0.035(1) Å C(5)–N(4)=C(3)–O(2)–C(1) fragment and C(9) atom deviation from this plane by 0.696(4) Å. Infinite chains of molecules along b axis are formed in the crystal by the intermolecular H-bond O(6)–H···N(4) with the parameters H···N(4) 1.89(4) Å and O(6)–H···N(4) 171(3)°. C(11) C(10) C(12) C(8) C(1) C(9) C(5) O(2) C(14) N(4) C(6) C(7) N(6) O(6) C(3) C(13) N OH 3 + H+ N OH N O R N H O R N OH N O R H 5 6 7 H – H+ 4 Scheme 3 Received: 22nd May 2002; Com. 02/1933

ISSN:0959-9436     

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 3, 2002 1 Electrochemistry of a cyclotrisilane and a cyclotrigermane. The first example of the electrochemical generation of a cyclotrisilane radical anion Ivan S. Orlov,a Mikhail P. Egorov,*a Oleg M. Nefedov,a Anna A. Moiseeva,b Kim P. Butin,b Detlev Ostendorfc and Manfred Weidenbruchc a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.Fax: +7 095 135 5328 b Department of Chemistry, M. V. Lomonosov Moscow State University, 119992 Moscow, Russian Federation c Fachbereich Chemie, Universiät Oldenburg, D-26111 Oldenburg, Germany 10.1070/MC2002v012n03ABEH001602 The radical anion of 1,1,2,2,3,3-hexa-tert-butylcyclotrisilane has been electrochemically generated in THF at room temperature.Strained cyclotrimetallanes of Group 14 elements are of great interest because of their intriguing structures and reactivities, and their important role as the precursors of the derivatives of low-coordinated silicon, germanium and tin compounds.1–3 The chemical properties of these small heterocycles have been intensively studied during the last two decades, but the electrochemistry of cyclotrimetallanes has not been adequately investigated. 1–4 In particular, the reduction potentials of cyclotrimetallanes have not been reported.At the same time, information on the redox potentials and the reversibility of electron attachment (detachment) processes is very important for the elucidation of the energy of frontier orbitals of cyclotrimetallanes and for the better understanding of their reactivity.The nature of radical ions generated upon electrochemical oxidation (reduction) can be studied using simultaneous electrochemical–ESR (SE–ESR) techniques,5 which were successfully used in the study of paramagnetic intermediates of the electrochemical oxidation (reduction) of a cyclotristannane.6 Here we report on an electrochemical and SE–ESR study of Group 14 element cyclotrimetallanes, 1,1,2,2,3,3-hexa-tert-butylcyclotrisilane 1 and 1,1,2,2,3,3-hexamesitylcyclotrigermane 2.According to cyclic voltammograms (CV), both of the compounds exhibit low oxidation and high reduction potentials (Table 1). The oxidation and reduction of cyclotrisilane 1 are quasi-reversible processes. A peak at 0.65 V (ipc /ipa = 0.45, peak A) on the reverse scan of a CV curve for oxidation and a peak at –2.27 V (ipa/ipc = 0.42, peak B) on the reverse scan of the CV curve for the reduction of 1 can be seen in Figure 1.Great differences between the direct and reverse peak potentials (360 mV for oxidation and 320 mV for reduction) suggest that, in fact, the reverse peaks can correspond to the reduction (peak A) or oxidation (peak B) of secondary products arising after the fragmentation of the primary radical ions.To detect the primary radical ions, compound 1 was studied by SE–ESR.† Upon the reduction of 1 at –2.59 V (in THF, 0.1 M Bu4NClO4 as a supporting electrolyte; Pt electrode; 20 °C) in the cavity of an ESR spectrometer, we detected the ESR spectrum of a paramagnetic species, g = 2.0039 (Figure 2).This spectrum is in good agreement with the simulated spectrum for the radical anion of 1, in which the unpaired electron is coupled with three equivalent silicon atoms with a(29Si) = 6.9 G. This value is close to that (7.0 G) reported1 for the radical anion of 1 generated by chemical reduction of 1 at < 200 K. At room temperature, the radical anion of 1 has a lifetime of about 1 min. Despite the quasi-reversible oxidation of 1 at 1.01 V, we failed to detect any primary or secondary paramagnetic species Si Si Si But But But But But But Ge Ge Ge Mes Mes Mes Mes Mes Mes 1 2 Table 1 Peak potentials for oxidation and reduction of compounds 1 and 2 (20 °C, THF, 0.1 M Bu4NClO4 as a supporting electrolyte; glassy carbon electrode; scan rate 200 mV s–1, Ag | AgCl | aq KCl (sat.) as a reference electrode).Compound Eox p Ered p 1 1.01 (1e)a –2.59 (1e)a 2 0.88 (1e) –2.76 (1e) aQuasi-reversible. † The electrochemical (cyclic voltammetry) experiments were carried out on a PI-50-1.1 potentiostat or a home-made potentiostat interfaced to an IBM PC. The working electrode was a glassy carbon disk (Æ1.8 mm), the reference electrode was Ag|AgCl|KCl (aq., sat.).The measurements were carried out in THF in the presence of 0.1 M Bu4NClO4 as a supporting electrolyte in an argon atmosphere. The electrochemical cell for SE–ESR measurements was described elsewhere.5 The ESR spectra were recorded using a Bruker EMX 6-1 spectrometer. Cyclotrisilane 1 and cyclotrigermane 2 were synthesised according to published procedures.7,8 B' A' A B 2 µA 1.0 0.0 –1.0 –2.0 E/V Figure 1 Cathodic (solid line) and anodic (dotted line) CV curves for cyclotrisilane 1 (10–3 M) in THF, at 10 °C, 0.1 M Bu4NClO4 as a supporting electrolyte; glassy carbon electrode; scan rate 0.5 V s–1.Figure 2 ESR spectrum of the radical anion of cyclotrisilane 1 electrochemically generated in THF at 20 °C.Mendeleev Communications Electronic Version, Issue 3, 2002 2 by SE–ESR techniques both at room temperature and at 200 K.Thus, the lifetime of the radical cation of 1 (in its cyclic or opened form) is too short. Note that sterically hindered 2,6- diethylphenyl (Dep) substituents can increase the lifetime of the radical cation; therefore, the open form of the radical cation of (Dep2Sn)3 can be detected by ESR spectroscopy.6 The oxidation and reduction of cyclotrigermane 2 are irreversible processes at 20 °C.This fact suggests very short lifetimes of the corresponding radical ions. Indeed, we were unable to detect any paramagnetic species upon the electrochemical oxidation of 2 at 0.88 V or on the reduction of 2 at –2.76 V directly in the cavity of the ESR spectrometer both at room temperature and at 200 K.This work was supported by the Russian Foundation for Basic Research (project nos. 00-15-97387 and 02-03-32148) and INTAS (grant no. 97-30344). References 1 M. Weidenbruch, Comments Inorg. Chem., 1986, 5, 247. 2 (a) T. Tsumuraya, S. A. Batcheller and S. Masamune, Angew. Chem., 1991, 103, 916; (b) T. Tsumuraya, S. A. Batcheller and S.Masamune, Angew. Chem., Int. Ed. Engl., 1991, 30, 902. 3 M. Weidenbruch, Chem. Rev., 1995, 95, 1479. 4 H. Watanabe, K. Yoshizumi, T. Muraoka, M. Kato, Y. Nagai and T. Sato, Chem. Lett., 1985, 1683. 5 A. V. Il’yasov and Yu. M. Kargin, Magn. Reson. Rev., 1993, 16, 135. 6 I. S. Orlov, M. P. Egorov, O. M. Nefedov, A. A. Moiseeva, K. P. Butin, and L. R. Sita, Abstracts of Papers of Xth International Conference on the Coordination and Organometallic Chemistry of Germanium, Tin and Lead, Universite Bordeaux, 2001, vol. 1, p. 40. 7 (a) A. Schäfer, M. Weidenbruch, K. Peters and H. G. von Schnering, Angew. Chem., 1984, 96, 311; (b) A. Schäfer, M.Weidenbruch, K. Peters and H. G. von Schnering, Angew. Chem., Int. Ed. Engl., 1984, 23, 302. 8 W. Ando and T. Tsumuraya, Tetrahedron Lett., 1986, 27, 3251. Received: 30th April 2002; Com. 02/1928

ISSN:0959-9436     

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 3, 2002 1 Regioselective interaction of â-aroylacrylic acids with 1,2-diaminoimidazoles Nadezhda N. Kolos, Tat’yana V. Beryozkina and Valeriy D. Orlov* V. N. Karazin Khar’kov National University, 61077 Khar’kov, Ukraine. E-mail: orlov@univer.kharkov.ua 10.1070/MC2002v012n03ABEH001581 á-Hetarylation products, which subsequently underwent cyclization into imidazopyridazines, were detected in the reactions of aroylacrylic acids with 1,2-diamino-4-phenylimidazole.The interaction of chalcones and á,â-dibromochalcones with 1,2-diaminoazoles containing hydrazine amino groups is a convenient method for the synthesis of azolopyridazine and azolopyrimidine systems.1–3 Based on indirect data, it was postulated1 that the reaction began at the step of Michael (or 1,4) addition of the azole to the enone (path A) or (if it is substituted) the endo nitrogen atom of diaminoazole (path B).2,3 However, previously, we failed to obtain direct evidence for this interaction, namely, to isolate its intermediates, which rapidly underwent cyclization at an amino group (Scheme 1).In this study, we found that the heating of compounds 1a–c with 1,2-diamino-4-phenylimidazole in ethanol for 10–15 min resulted in the formation of compounds 3a–c (which occur as zwitterions), the á-hetarylation products of acids 1a–c with the C-5 atom of the imidazole ring (Scheme 2).The structures of compounds 3a–c were confirmed by 1H NMR and IR-spectroscopic data.† Thus, the 1H NMR spectra exhibited pronounced signals due to protons of both aromatic nuclei at 8.01–7.18 ppm; a singlet due to protons of the amino group with d 6.17-6.10 ppm, which disappeared after exchange for deuterium; a group of signals due to protons of the CH2–CH unit with a typical ABX structure (two doublets and a doublet of doublets: JAB 16.8 Hz, JAX 0 Hz and JBX 6.4 Hz); and (in 3a) a singlet due to protons of the methyl group.The protons of the ammonium group manifested themselves as a broadened (up to 1 ppm) signal (because of proton exchange with H2O present in [2H6]DMSO) at 3–4 ppm. In the IR spectra of compounds 3a–c, the ionised carboxyl group manifests itself as absorption bands at 1360 and 1570 cm–1, and the NH3 + group, as a broad band at 2980 cm–1.4 Bands due to the amino group at 3340 and 3440 cm–1 and a band due to the carbonyl group (~1700 cm–1) were also observed.Thus, we were the first to detect the arylation products of enone systems. Compounds 3a–c were found to be stable; this is likely due to their betaine structures. All attempts to cyclise them on boiling in alcohols (ethanol and isopropanol), benzene, toluene, and chloroform were unsuccessful.Compounds 3a–c were cyclised into imidazo[1,5-b]pyridazines 4a–c‡ only by boiling in dimethylformamide. The reaction was accelerated in the presence of HCl, and it was accompanied by decarboxylation and aromatization. Compound 4d was formed directly, without the betaine intermediate being isolated. The structures of compounds 4a–d were also supported by 1H NMR and IR spectroscopy.The 1H NMR spectra of products 4a–d exhibited doublets due to CH protons of the pyridazine ring (J 10 Hz), a singlet due to the amino group with d 6.4 ppm, and multiplets due to protons of both aromatic nuclei. The IR spectra of compounds 4a–d exhibited both bands due to the amino group and no absorption bands due to the betaine unit and the carbonyl group. The stepwise cyclocondensation of aminoazoles with á,â- unsaturated ketones, which was postulated previously1–3 and experimentally supported in this work, primarily indicates that the nucleophilicity of amino groups is lower than the nucleophilicity of azole endo atoms N or C.† A solution of acid 1a (0.01 mol, 1.76 g) and diamine 2a (0.01 mol, 1.73 g) in 15 ml of EtOH was boiled for 10–15 min.After cooling, the precipitate was filtered off and crystallised from EtOH–H2O (1:1); 80% of product 3a was obtained. Compounds 3b and 3c in 85 and 83% yields, respectively, were synthesised in a similar manner. 3a: mp 210 °C. 1H NMR (200 MHz, [2H6]DMSO) d: 8.00 (dd, 2H), 7.80 (d, 2H), 7.48–7.15 (m, 6H), 6.17 (s, 2H), 4.40 (d, 1H), 3.46 (d, 1H), 2.81 (dd, 1H). IR (KBr, n/cm–1): 3440, 3328, 2980, 1700, 1570, 1360. 3b: mp 231 °C. 1H NMR (200 MHz, [2H6]DMSO) d: 8.01 (dd, 2H), 7.75 (d, 2H), 7.54–7.46 (m, 5H), 6.14 (s, 2H), 4.43 (d, 1H), 3.47 (d, 1H), 2.76 (dd, 1H). IR (KBr, n/cm–1): 3440, 3336, 2980, 1702, 1560, 1360. 3c: mp 204 °C. 1H NMR (200 MHz, [2H6]DMSO) d: 7.91 (d, 2H), 7.74 (d, 2H), 7.51 (d, 2H), 7.28 (d, 2H), 6.10 (s, 2H), 4.41 (d, 1H), 3.44 (d, 1H), 2.83 (dd, 1H), 2.36 (s, 3H).IR (KBr, n/cm–1): 3453, 3350, 2980, 1700, 1565, 1370. Ar' Ar O Y N N NH2 NH2 R Ar' Y N N NH2 NH2 Ar O Y N N NH2 NH R Ar Ar' O N N N Y NH2 Ar Ar' N N N R Y Ar Ar' A B R = H R = Ph, NH2 Y = C–Ph Scheme 1 R O OH O N NH2 N Ar NH2 EtOH R O N NH3 N Ar NH2 O O DMF, H+ R N N N Ar NH2 1a–c 2a,b 3a–c 4a–d a R = H b R = 4-Me c R = 4-Cl a Ar = Ph b Ar = 4-BrC6H4 a R = H, Ar = Ph b R = H, Ar = 4-BrC6H4 c R = 4-Me, Ar = 4-BrC6H4 d R = 4-Cl, Ar = Ph Scheme 2Mendeleev Communications Electronic Version, Issue 3, 2002 2 References 1 N.N. Kolos, V. D. Orlov, B. V. Paponov and V. N. Baumer, Khim. Geterotsikl. Soedin., 1998, 1397 [Chem. Heterocycl. Compd. (Engl. Transl.), 1998, 34, 1189]. 2 N. N. Kolos, V. D. Orlov, B. V. Paponov and O. V. Shishkin, Khim. Geterotsikl.Soedin., 1999, 1388 [Chem. Heterocycl. Compd. (Engl. Transl.), 1999, 35, 1207]. 3 N. N. Kolos, V. D. Orlov and B. V. Paponov, Khim. Geterotsikl. Soedin., in press. 4 L. G. Bellamy, Infrakrasnye spektry slozhnykh molekul (The Infra-red Spectra of Complex Molecules), Izdatel’stvo Inostrannoi Literatury, Moscow, 1963, pp. 250, 337 (in Russian). ‡ Compound 3a (0.01 mol, 3.5 g) was dissolved in 20 ml of DMF and 3 ml of concentrated HCl were added.The mixture was boiled for 2 h, cooled and neutralised with a 10% NaOH solution. The product was filtered off and crystallised from EtOH; 25% of imidazopyridazine 4a was obtained. Compounds 4b and 4c in 50 and 30% yields, respectively, were synthesised in a similar manner. 4a: mp 224 °C. 1H NMR (200MHz, [2H6]DMSO) d: 8.25 (d, 1H), 8.20–7.52 (m, 10H), 7.03 (d, 1H), 6.45 (s, 2H).IR (KBr, n/cm–1): 3403, 3225, 1635. 4b: mp 233–234 °C. 1H NMR (200 MHz, [2H6]DMSO) d: 8.24 (d, 1H), 8.17–7.50 (m, 9H), 7.03 (d, 1H), 6.43 (s, 2H). IR (KBr, n/cm–1): 3405, 3272, 1635. 4c: mp 231 °C. 1H NMR (200 MHz, [2H6]DMSO) d: 8.25 (d, 1H), 8.06 (d, 2H), 7.80 (d, 2H), 7.55 (d, 2H), 7.33 (d, 2H), 7.02 (d, 1H), 6.40 (s, 2H). IR (KBr, n/cm–1): 3430, 3290, 1640. 4d: a solution of acid 1c (0.01 mol, 1.76 g), diamine 2a (0.01 mol, 1.73 g) and 3 ml of concentrated HCl in 10 ml of DMF was boiled for 2–3 h. After cooling, the product was filtered off and crystallised from EtOH. Yield 25%, mp 207 °C. 1H NMR (200 MHz, [2H6]DMSO) d: 8.25 (d, 1H), 8.18 (d, 2H), 7.84 (d, 2H), 7.57 (d, 2H), 7.43–7.17 (m, 3H), 6.97 (d, 1H), 6.43 (s, 2H). IR (KBr, n/cm–1): 3405, 3280, 1642. Received: 18th March 2002; Com. 02/1907

ISSN:0959-9436     

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 3, 2002 1 Effect of formate on the radiolytic degradation of nitrate in deaerated aqueous solutions Alexandr V. Ponomarev, Alexei V. Bludenko and Igor E. Makarov* Institute of Physical Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation. Fax: +7 095 429 9244 10.1070/MC2002v012n03ABEH001583 Nitrate ions are irreversibly reduced in dilute aqueous solutions in the presence of formate under the action of an electron beam.Nitrate and nitrite ions are abundant components of industrial and municipal wastewater. High solubility, stability and toxicity of nitrates and nitrites make their removal from wastewater vital, and this is one of the most difficult environmental problems. Unfortunately, the traditional methods of wastewater treatment appear insufficiently effective to decompose nitrates and nitrites.Earlier,1 it was found that in aqueous solutions the irreversible removal of nitrate and nitrite can be performed under the action of an electron beam in the presence of effective scavengers of OH radicals. Sulfite was considered as a scavenger. In actual practice, sulfite is not an optimal supplementary reagent for the removal of nitrite and nitrate because it is an unwanted water pollutant.Under radiolysis, a significant part of sulfite is transformed to less harmful sulfate. However, the total surplus mineralization of water caused by additional sulfite and sulfate is practically not eliminated by radiolytic treatment. It is reasonable to produce the combined presence of nitrate and sulfite by mixing two wastewater types enriched by nitrate and sulfite, respectively.The application of dry sulfite or its concentrated solution is frequently unreasonable because of an unavoidable increase in the mineralization of nitrate-containing wastewater under treatment. As a rule, the supplementary scavenger should not aggravate the properties of wastewater, and it should fit the following basic requirements: (i) harmlessness— the products of radiolytic conversion of the scavenger should be non-toxic and inert; (ii) availability —the scavenger should not be expensive and limited; (iii) productivity — the required effect should be reached by a minimum amount of the scavenger at a minimum applied dose.In this work, we used the formate ion as a scavenger of OH radicals to study the mechanism of nitrate decomposition.Formate, similarly to sulfite, has a high reactivity to OH radicals (for sulfite, k = 1.5×109 dm3 mol–1 s–1): and is inert to the reducing products of water radiolysis.2–4 The rate constant of hydrated electron reaction with formate does not exceed 1×104 dm3 mol–1 s–1, and the reaction of formate with the H atom is one order of magnitude slower than reaction (1): Moreover, formate is not resistant to radiation, and it is irreversibly decomposed to CO2 and H2O.3,4 That is, the use of formate should cause, in particular, smaller mineralization of wastewater.Thus, formate is a more promising scavenger of OH radicals than sulfite. The model solutions were prepared from NaNO3 and HCOOLi of extra pure grade.A Specord M40 spectrophotometer was used for optical measurements. Nitrogen compounds were determined at ambient temperature by standard procedures.5,6 Oxalic acid (oxalate) was determined using the copper–benzidine complex.7,8 A U-12F linear accelerator was used as a source of quasicontinuous electron radiation (electron energy of 5 MeV, pulse duration of 2.3 µs, pulsing frequency of 400 Hz and dose rate of 10 Gy s–1).The solutions were deaerated by bubbling pure argon for 45 min. The solutions were irradiated in glass ampoules (the solution volume was 10 ml and the volume of a gas phase was 5 ml). For measuring the nitrate (nitrite) concentration, the irradiated solutions were stored at 60 °C for 40 min before analysis to remove volatile nitrogen compounds. One of the final products of the radiolytic conversion of formate in deaerated aqueous solutions is oxalate, the product of combination of ·COO– radical anions (2k = 1.5×109 dm3 mol–1 s–1).9 The yield of oxalate in a deaerated aqueous solution increases with initial formate concentration and at a concentration of 0.002 mol dm–3 reaches 0.153 µmol J–1 (Figure 1, curve 1).This value indicates the practically complete capture of OH radicals in the bulk of irradiated water after finishing spur processes (0.3 µmol J–1)2,10,11 by formate. It additionally testifies that OH radicals are the main precursors of oxalate ions, and reaction (1) can effectively suppress other processes with the participation of OH radicals.In the presence of nitrate (1×10–4 mol dm–3), k = 3.1×109 dm3 mol–1 s–1 OH + HCOO– ® H2O + COO– (1) k = 3.0×108 dm3 mol–1 s–1 H + HCOO– ® H2 + COO– (2) Figure 1 Influence of formate concentration on the radiation-chemical yield of oxalate formation in aqueous solutions irradiated at 2 kGy: (1) without nitrate; (2) with 1×10–4 mol dm–3 nitrate. 0.15 0.12 0.09 0.06 0.03 0.00 0 5 10 15 20 1 2 Radiation-chemical yield/µmol J–1 [HCOO–]/10–4 mol dm–3 Figure 2 Optical absorption spectra of initial (1, 3, 5 and 7) and irradiated (2 kGy) (2, 4, 6 and 8) deaerated aqueous solutions: (1, 2) 2×10–4 mol dm–3 formate; (3, 4) 2×10–4 mol dm–3 formate + 1×10–4 mol dm–3 nitrate; (5, 6) 5×10–4 mol dm–3 formate; (7, 8) 5×10–4 mol dm–3 formate + 1×10–4 mol dm–3 nitrate. Insert: the influence of formate concentration on the combined optical absorption of NO3 – and NO2 – at 202 nm in a 1×10–4 mol dm–3 nitrate solution at 2 kGy. 1.0 0.8 0.6 0.4 0.2 0.0 200 210 220 Absorbance l/nm 7 3 6 4 8 2 5 0.8 0.6 0.4 0.2 0.0 0 3 6 9 Absorbance [HCOO–]/10–4 mol dm–3 1Mendeleev Communications Electronic Version, Issue 3, 2002 2 the dependence of the radiation-chemical yield of oxalate essentially varies.The noticeable accumulation of oxalate begins only at a formate concentration higher than 3.5×10–4 mol dm–3. In turn, the limiting yield of oxalate in the presence of nitrate is noticeably lower. It demonstrates an essential effect of small nitrate admixtures on reactions with the participation of OH radicals. Nitrate has a very low activity to OH radicals (k < < 5×105 dm3 mol–1 s–1).The decomposition of nitrate is mainly caused by the reactions with hydrated electrons e– aq and H atoms:2,10,11 NO3 – + e– aq ® NO3 2– k = 9.7×109 dm3 mol–1 s–1 (3) NO3 – + H ® HNO3 – k = 1.4×106 dm3 mol–1 s–1 (4) NO3 2– + H2O ® NO· 2 + 2OH– k = 1.0×103 s–1 (5) HNO3 – ® NO2 · + OH– k = 2.3×102 s–1 (6) 2NO2 · ® N2O4 k = 7.6×107 dm3 mol–1 s–1 (7) N2O4 + H2O ® NO3 – + NO2 – + 2H+ k = 1.0×103 s–1 (8) NO· 2 + e– aq ® NO2 – k = 1.0×1010 dm3 mol–1 s–1 (9) NO· 2 + H ® H+ + NO2 – k = 1.0×109 dm3 mol–1 s–1 (10) NO2 · + NO ® N2O3 k = 1.1×109 dm3 mol–1 s–1 (11) N2O3 + H2O ® 2NO2 – + 2H+ k = 5.3×102 s–1 (12) NO2 – + e– aq ® NO2 2– k = 4.2×109 dm3 mol–1 s–1 (13) NO2 2– + H2O ® NO + 2OH– k = 1.0×103 s–1 (14) NO2 – + H ® NO + OH– k = 7.1×108 dm3 mol–1 s–1 (15) The difference in the dynamics of oxalate accumulation shown in Figure 1 allows one to propose that the radical anion ·COO– participates in the reducing conversion of nitrate.However, in the deficiency of a scavenger, OH radicals effectively react with the products of reactions (3)–(11) and again convert them to nitrate:2,10,11 NO2 – + OH ® NO2 · + OH– k = 1.0×1010 dm3 mol–1 s–1 (16) NO2 · + OH ® HNO3 k = 1.0×1010 dm3 mol–1 s–1 (17) OH + OH ® H2O2 2k = 1.06×1010 dm3 mol–1 s–1 (18) NO2 – + H2O2 ® NO3 – + H2O k £ 4 dm3 mol–1 s–1 at pH ~7 (19) NO + OH ® HNO2 k = 2.0×1010 dm3 mol–1 s–1 (20) A selective scavenger of OH radicals is necessary to suppress these processes.As it can be seen in Figure 1 (curve 2), a formate concentration higher than 3.5×10–4 mol dm–3 is sufficient to suppress reactions (16)–(20) by reaction (1).The kinetics of nitrate and nitrite conversion can be estimated by spectrophotometry (Figure 2). Formate at concentrations of 2×10–4 and 5×10–4 mol dm–3 has rather low absorption at 195– 230 nm (curves 1 and 5). This absorption increases after irradiation due to the higher molar absorption coefficient of oxalate (curves 2 and 6).Contrary to formate, the smaller amount of nitrate is displayed by an intense band with a maximum at 201– 203 nm (curves 3 and 7). The irradiation of a solution simultaneously containing nitrate and formate to 2 kGy results in a decrease in absorption. In the presence of 2×10–4 mol dm–3 of formate, the absorption at 202 nm is almost halved (curve 4), and in the presence of 5×10–4 mol dm–3 of formate the characteristic absorption band of nitrate disappeared (curve 8).The residual spectrum in the latter case becomes similar to the spectrum of the irradiated 5×10–4 mol dm–3 formate solution (curve 6). As follows from a comparison of curves 6 and 8, in the presence of nitrate under irradiation, this absorption is lower than that of an individual formate solution. The insert in Figure 2 shows the dependence of the combined optical absorption of NO3 – and NO2 – ions in an irradiated 1×10–4 mol dm–3 nitrate solution on formate concentration.It can be seen that for the almost complete disappearance of the characteristic absorption of nitrate and nitrite at 2 kGy a five-fold excess of formate is required.Figure 3 indicates that the degradation of nitrate at a formate concentration of (2–5)×10–4 mol dm–3 is rather effective. At 5×10–4 mol dm–3 of formate and a dose of 2 kGy, nitrate is removed practically completely. From the initial slope of curve 2 the yield of nitrate decomposition is estimated at 0.077± 0.006 µmol J–1. The same yield is observed at the beginning of curve 1 at a formate concentration of 2×10–4 mol dm–3.However, in the latter case, the dependence of absorption passes through a minimum at 1–1.5 kGy (about 40% of the initial absorption); then, at 1.5–3 kGy an increase is observed, and at higher doses the absorption is stabilised at a level of 60% of the initial value. A minimum in curve 1 is due to the transformation of a significant part of nitrate to nitrite at doses less than 3 kGy.The formation of nitrite resulted from reactions (8)–(10) and (12). Nitrite is known to exhibit the molar absorption coefficient almost twice lower than that of nitrate. Figure 2 (curve 4) shows that the optical absorption maximum is shifted to 208–209 nm, being characteristic of nitrite. The results of this study demonstrate that formate provides rather effective radiolytic removal of nitrates and nitrites from aqueous solutions.Practically complete decomposition of nitrate at a dose of 2 kGy is observed at a 4.5 to 5-fold excess of formate concentration over nitrate. Thus, the efficiency of formate as an OH scavenger is higher than that of sulfite.1 The presence of formate protects the solution from reverse radiolytic reactions (16)–(20) under irradiation.Formate is a frequently occurring component of wash water and wastewater (for example, in semiconductor, chemical, papermill and metallurgical industries). Such flows can serve for the dilution of nitrate-containing wastewater and consequent combined electron-beam treatment. In this work, the removal of nitrate under anaerobic conditions was considered.The removal of nitrates under electron-beam treatment in the presence of air seems more reasonable, and it will be discussed elsewhere. References 1 H. S. Shin, Y. R. Kim and A. V. Ponomarev, Mendeleev Commun., 2001, 21. 2 G. V. Buxton and C. L. Greenstock, J. Phys. Chem. Ref. Data, 1983, 17, 886. 3 D. C. Kim, D. X.Kim, D. K. Kim, Y. R. Kim, I. E. Makarov, A. K. Pikaev, A. V. Ponomarev, I. T. Seo and B. S. Han, Khim. Vys. Energ., 1999, 33, 413 [High Energy Chem. (Engl. Transl.), 1999, 33, 359]. 4 L. I. Kartasheva, V. N. Chulkov, O. A. Didenko and A. K. Pikaev, Khim. Vys. Energ., 2000, 34, 467 [High Energy Chem. (Engl. Transl.), 2000, 34, 409]. 5 Standard Methods for the Examination of Water and Wastewater, eds.A. D. Eaton, L. S. Clesceri and A. E. Greenberg, American Public Health Association, 19th edn., 1995, pp. 850–857. 6 A. P. Kreshkov and A. A. Yaroslavtsev, Analiticheskaya khimiya. Kolichestvennyi analiz (Analytical Chemistry. Qualitative Analysis), Khimiya, Leningrad, 1975, pp. 332–336 (in Russian). 7 Z. D. Draganic, Anal. Chim. Acta, 1963, 28, 394. 8 N. W. Holm and K. Sehested, Adv. Chem. Ser., 1968, 81, 568. 9 E. J. Hart and A. Henglein, J. Phys. Chem., 1985, 89, 4342. 10 A. B. Ross and P. Neta, Rate Constants for Reactions of Inorganic Radicals in Aqueous Solution, NSRD-NBS 65, Washington, DC, 1979. 11 P. Neta, R. E. Huie and A. B. Ross, J. Phys. Chem. Ref. Data, 1988, 17, 1027. 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 Dose/kGy Absorbance 1 2 Figure 3 Dose effect on the combined optical absorption of NO3 – and NO2 – ions at 202 nm in a deaerated aqueous solution (1×10–4 mol dm–3) of nitrate at an initial formate concentration of (1) 2×10–4 or (2) 5×10–4 mol dm–3. Received: 21st March 2002; Com. 02/1909

ISSN:0959-9436     

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 3, 2002 1 Synthesis of 1-(substituted phenyl)-2-phenyl-4-(2'-hydroxy-3'-iodo-5'-chloro- benzylidene)imidazol-5-ones Sudhakar R. Bhusare,a Pratap S. Patil,a Vishal P. Chavan,b Rajendra P. Pawar,*a Baburao M. Bhawalc and Yeshwant B. Vibhute*d a Organic Chemistry Synthesis Laboratory, Dnyanopasak College, Parbhani 431401, India. E-mail: rppawar@yahoo.com b Department of Chemistry, Dr.B. A. M. University, Aurangabad 431004, India c Organic Chemistry Synthesis Division, National Chemical Laboratory, Pune 411008, India d P. G. Department of Chemistry, Yashwant Mahavidyalaya, Nanded 431602, India 10.1070/MC2002v012n03ABEH001584 The title compounds were prepared by treating a mixture of 5-oxazolone derivatives with substituted aromatic amines in the presence of a zeolite (Y-H) catalyst.Imidazolones exhibit several pharmacological activities.1–4 Imidazolidinones have been reported to possess a potent CNS depressant activity. Some imidazoles and substituted imidazolones have been reported to possess monoamine oxidase (MAO) inhibitory and anticonvulsant activities.5,6 This observation prompted us to synthesise new 1-(substituted phenyl)- 2-phenyl-4-(2'-hydroxy-3'-iodo-5'-chlorobenzylidene)imidazol- 5-one by a new method.Earlier, imidazolones 4 have been prepared by heating a mixture of 5-oxazolone derivative 3† with aromatic amines in the presence of pyridine for 10–15 h. The yield of imidazolones 4 was very low, and the reaction took a long time.7–9 We synthesised new imidazolones 4‡ by the condensation of aromatic amines with compound 3 in the presence of zeolite (Y-H) (Scheme 1).The reaction took place in 3–5 h with excellent yields. The 5-oxazolone derivative (ozalactone) was prepared by the condensation of hippuric acid with 2-hydroxy-3-iodo- 5-chlorobenzaldehyde in the presence of sodium acetate and acetic anhydride. The compounds were crystallised from ethanol and identified by elemental analysis and spectroscopic data.We are thankful to W. N. Jadhav, U. R. Kalkote and P. P. Wadgaonkar for their valuable guidance. References 1 W. B. Wright and H. J. Brabander, J. Org. Chem., 1961, 26, 4051. 2 U. Niedbalia and I. Buettcher, Ger. Patent 2856909, 1980 (Chem. Abstr., 1981, 94, 15732). 3 K. Pande, K. R. Kalsi and T. N.Bhalla, Pharmazie, 1987, 42, 269. 4 W. B. Wright, H. S. Brabander, R. A. Hardy and A. C. Osterberg, J. Med. Chem., 1966, 9, 852. 5 A. Luigi, M. Alfonso, R. Pierluigi, G. Afro, Z. Enzo, De. T. Nicola and M. Walter, J. Med. Chem., 1969, 12, 122. 6 M. Verma, A. K. Charturvedi, A. Chaudhry and S. S. Parmar, J. Parm. Sci., 1974, 463, 1740. † Melting points (uncorrected) were determined in open capillary tubes.The purity of compounds was checked by TLC using silica gel G. The IR spectra in Nujol were recorded on a Perkin–Elmer 237 spectrophotometer. The 1H NMR spectra in CDCl3 were recorded on a Perkin–Elmer R-32 spectrometer using TMS as an internal standard. General procedure for the preparation of 2-phenyl-4-(2'-hydroxy-3'- iodo-5-chlorobenzylidene)oxazol-5-one 3: 2-hydroxy-3-iodo-5-chlorobenzaldehyde (10 mmol), hippuric acid (10 mmol), acetic anhydride (30 mmol) and sodium acetate (10 mmol) were heated on an electric hot plate with continuously shaking in a conical flask.As soon as the mixture was liquified completely, the flask was heated in a water bath for 2 h. Ethanol (5 ml) was added slowly to the contents of the flask, and the mixture was allowed to stand overnight.The separated crystalline solid was filtered off and successively washed with ice-cold ethanol and hot water to obtain 3; yield 347 mg (82%), mp 127 °C. 1HNMR, d: 6.8 (s, 1H, Ph–CH), 7.2–7.8 (m, 7H, Ar–H), 9.9 (s, 1H, Ar–OH). IR, n/cm–1: 1625–1605, 1610–1580, 1660–1650, 3720. Found (%): C, 48.45; H, 2.84; N, 3.32. Calc. for C16H9NO3ICl (%): C, 48.48; H, 2.87; N, 3.33.a R = H b R = 3-NO2 c R = 4-NO2 d R = 4-Br e R = 4-I f R = 2-OMe g R = 3-OMe h R = 4-OMe i R = 2-Cl j R = 4-Cl k R = 3-Me l R = 4-Me m R = 2-COOH n R = 4-COOH Scheme 1 OH CHO Cl I O N H COOH OH Cl I N O O i, MeCOONa ii, (MeCO)2O OH Cl I N N O R ArNH2 Zeolite (Y-H) 1 2 3 4a– n ‡ General procedure for the preparation of 1-(substituted phenyl)-2- phenyl-4-(2'-hydroxy-3'-iodo-5'-chlorobenzylidene)imidazole-5-one 4: oxazolone 3 (10 mmol) was heated with an equimolar quantity of an aromatic amine in pyridine (10 mmol) with a zeolite (Y-H) catalyst in an oil bath at 150 °C for 3–5 h.The excess of pyridine was distilled off. The mixture was cooled and poured into crushed ice and HCl. The product was filtered off and crystallised from ethanol to give 4a–n. 4a: yield 95%, mp 130 °C. 1H NMR, d: 6.9 (s, 1H, Ph–CH), 7.1–8.2 (m, 12H, Ar–H), 9.7 (s, 1H, Ar–OH). IR, n/cm–1: 1625–1610, 1615–1580, 1655–1635, 3680. Found (%): C, 52.72; H, 2.77; N, 5.55. Calc. for C22H14N2O2ICl (%): C, 52.77; H, 2.82; N, 5.59. 4b: yield 85%, mp 105 °C. 1H NMR, d: 6.7 (s, 1H, Ph–CH), 7.2–8.2 (m, 11H, Ar–H), 9.9 (s, 1H, Ar–OH). IR, n/cm–1: 1620–1610, 1615– 1575, 1650–1635, 3680.Found (%): C, 48.38; H, 2.36; N, 7.65. Calc. for C22H13N3O4ICl (%): C, 48.42; H, 2.40; N, 7.70. 4c: yield 92%, mp 160 °C. 1H NMR, d: 6.9 (s, 1H, Ph–CH), 7.3–8.4 (m, 11H, Ar–H), 9.8 (s, 1H, Ar–OH). IR, n/cm–1: 1620–1615, 1618–1585, 1650–1635, 3675. Found (%): C, 48.40; H, 2.35; N, 7.66. Calc. for C22H13N3O4ICl (%): C, 48.42; H, 2.40; N, 7.70. 4d: yield 98%, mp 145 °C. 1H NMR, d: 7.0 (s, 1H, Ph–CH), 7.0–8.2 (m, 11H, Ar–H), 9.7 (s, 1H, Ar–OH). IR, n/cm–1: 1625–1610, 1615– 1585, 1650–1635, 3670. Found (%): C, 45.54; H, 2.22; N, 4.75. Calc. for C22H13N2O2BrICl (%): C, 45.59; H, 2.26; N, 4.83. 4e: yield 93%, mp 111 °C. 1H NMR, d: 6.8 (s, 1H, Ph–CH), 7.1–8.3 (m, 11H, Ar–H), 9.6 (s, 1H, Ar–OH). IR, n/cm–1: 1620–1610, 1620– 1585, 1655–1630, 3690. Found (%): C, 42.12; H, 2.02; N, 4.43.Calc. for C22H13N2O2I2Cl (%): C, 42.17; H, 2.09; N, 4.47. 4f: yield 90%, mp 118 °C. 1H NMR, d: 3.9 (s, 3H, OMe), 6.8 (s, 1H, Ph–CH), 7.2–8.4 (m, 11H, Ar–H), 9.9 (s, 1H, Ar–OH). IR, n/cm–1: 1630–1610, 1615–1580, 1665–1635, 3670. Found (%): C, 52.00; H, 2.98; N, 5.23. Calc. for C23H16N2O3ICl (%): C, 52.05; H, 3.04; N, 5.28.Mendeleev Communications Electronic Version, Issue 3, 2002 2 7 M.A. Abdallah, M. E. Zayed and A. S. Shawali, Indian J. Chem., 2001, 40B, 187. 8 M. M. H. Arief, Indian J. Chem., 1998, 37B, 558. 9 M. D. Shah, N. C. Desai, K. K. Awasthi and A. K. Saxena, Indian J. Chem., 2001, 40B, 201. Received: 25th March 2002; Com. 02/1910 4g: yield 89%, mp 95 °C. 1H NMR, d: 4.1 (s, 3H, OMe), 6.6 (s, 1H, Ph–CH), 7.0–8.5 (m, 11H, Ar–H), 9.5 (s, 1H, Ar–OH).IR, n/cm–1: 1620–1610, 1615–1575, 1655–1645, 3675. Found (%): C, 52.08; H, 2.95; N, 5.21. Calc. for C23H16N2O3ICl (%): C, 52.05; H, 3.04; N, 5.28. 4h: yield 95%, mp 135 °C. 1H NMR, d: 4.0 (s, 3H, OMe), 7.0 (s, 1H, Ph–CH), 7.3–8.3 (m, 11H, Ar–H), 9.9 (s, 1H, Ar–OH). IR, n/cm–1: 1625–1610, 1615–1580, 1655–1635, 3680. Found (%): C, 52.00; H, 3.01; N, 5.24. Calc.for C23H16N2O3ICl (%): C, 52.05; H, 3.04; N, 5.28. 4i: yield 86%, mp 121 °C. 1H NMR, d: 7.0 (s, 1H, Ph–CH), 7.4–8.4 (m, 11H, Ar–H), 9.7 (s, 1H, Ar–OH). IR, n/cm–1: 1625–1615, 1620– 1580, 1645–1635, 3685. Found (%): C, 49.35; H, 2.40; N, 5.20. Calc. for C22H13N2O2ICl2 (%): C, 49.38; H, 2.45; N, 5.23. 4j: yield 93%, mp 147 °C. 1H NMR, d: 6.9 (s, 1H, Ph–CH), 7.2–8.2 (m, 11H, Ar–H), 9.8 (s, 1H, Ar–OH).IR, n/cm–1: 1625–1610, 1615– 1580, 1655–1635, 3680. Found (%): C, 49.33; H, 2.42; N, 5.18. Calc. for C22H13N2O2ICl2 (%): C, 49.38; H, 2.45; N, 5.23. 4k: yield 97%, mp 127 °C. 1H NMR, d: 2.4 (s, 3H, Me), 6.6 (s, 1H, Ph–CH), 7.2–8.2 (m, 11H, Ar–H), 9.6 (s, 1H, Ar–OH). IR, n/cm–1: 1625–1615, 1620–1575, 1650–1635, 3690. Found (%): C, 53.64; H, 3.09; N, 5.88.Calc. for C23H16N2O2ICl (%): C, 53.67; H, 3.13; N, 5.94. 4l: yield 90%, mp 155 °C. 1H NMR, d: 2.3 (s, 3H, Me), 6.7 (s, 1H, Ph–CH), 7.2–8.0 (m, 11H, Ar–H), 9.7 (s, 1H, Ar–OH). IR, n/cm–1: 1625–1610, 1620–1580, 1655–1635, 3685. Found (%): C, 53.61; H, 3.08; N, 5.89. Calc. for C23H16N2O2ICl (%): C, 53.67; H, 3.13; N, 5.94. 4m: yield 85%, mp 170 °C. 1H NMR, d: 6.6 (s, 1H, Ph–CH), 7.2–8.3 (m, 11H, Ar–H), 9.8 (s, 1H, Ar–OH), 10.2 (s, 1H, COOH). IR, n/cm–1: 1625–1610, 1630–1580, 1655–1645, 2955–2670, 3685. Found (%): C, 50.66; H, 2.55; N, 5.10. Calc. for C23H14N2O4ICl (%): C, 50.71; H, 2.59; N, 5.14. 4n: yield 91%, mp 165 °C. 1H NMR, d: 6.8 (s, 1H, Ph–CH), 7.2–8.2 (m, 11H, Ar–H), 9.8 (s, 1H, Ar–OH), 10.5 (s, 1H, COOH). IR, n/cm–1: 1625–1610, 1635–1580, 1650–1645, 2975–2575, 3675. Found (%): C, 50.65; H, 2.53; N, 5.11. Calc. for C23H14N2O4ICl (%): C, 50.71; H, 2.59; N, 5.14.

ISSN:0959-9436     

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 3, 2002 1 Preparation of 1,2-bis(3,4-dicyanophenoxymethyl)benzene and the binuclear zinc phthalocyanine derived from it Alexander Yu. Tolbin,a Alexey V. Ivanov,b Larisa G. Tomilova*b and Nikolai S. Zefirovb a Department of Chemistry, M. V. Lomonosov Moscow State University, 119992 Moscow, Russian Federation. Fax: +7 095 939 0290; e-mail: tom@org.chem.msu.su b Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka, Moscow Region.Fax: +7 095 785 7024 10.1070/MC2002v012n03ABEH001573 A method of synthesis of 1,2-bis(3,4-dicyanophenoxymethyl)benzene from the 1,2-bis(hydroxymethyl)benzene and 4-nitrophthalodinitrile is developed. Its tetramerization with Zn(OAc)2·2H2O gives a binuclear zinc phthalocyanine of a new type, containing four o-phenylidene bridges. The use of microwave heating decreases reaction time and increases yield.The synthesis and study of binuclear phthalocyanines is one of the priorities of modern phthalocyanine chemistry. Due to interaction between phthalocyanine rings and a covalent bridge between them, binuclear phthalocyanines can have specific electro- and photocatalytic properties.1,2 Recently, the attention of investigators has been attracted to binuclear phthalocyanines linked by only one bridge, called as the clamshell.2 At the same time, the synthesis and properties of binuclear phthalocyanines with a greater number of cross-links are not described in the literature.In order to obtain a new type of binuclear phthalocyanine, we carried out the synthesis of 1,2-bis(3,4-dicyanophenoxymethyl)- benzene 1 according to Scheme 1† by the common method1 of nucleophilic substitution of an activated nitro group in an aromatic ring. 1,2-Bis(hydroxymethyl)benzene 2 has been previously synthesised. 3 4-Nitrophthalodinitrile 3 was obtained according to Scheme 2. To obtain 4-nitrophthalimide, we used NH4NO3 in concentrated H2SO4.‡ Stages ii and iii were made by published methods,4,5 respectively. There are published data on the synthesis and properties of binuclear phthalocyanines linked by one covalent bridge.1–3 Such phthalocyanines were synthesised by the interaction of bisphthalodinitriles with a large excess of phthalodinitrile or the corresponding derivatives of o-phthalic acid.Under these conditions, a large amount of monophthalocyanine was obtained as a by-product. To eliminate a possibility of the formation of phthalocyanines with a different structure, we used only one phthalodinitrile 1 for the formation of binuclear phthalocyanine (Scheme 3).§ Phthalocyanine 4 was purified by TLC (Silufol UV-254, eluted with MeOH, then CHCl3). It is readily soluble in the majority of organic solvents.In the electronic absorption spectrum (Figure 1), the Q-band occurs at 680 nm, characteristic of a D4h symmetry, and the Sort-band at 352 nm. In the MALDI-TOF¶ MS spectrum (Figure 2) there is a peak of the molecular ion 1692 (M+, the molecular weight of phthalocyanine 4 is 1692.392). As a peak with m/z 846 is absent in the mass spectrum, we conclude that the side-strapped monophthalocyanine is not present.Recently, we reported6 on the synthesis of mono- and bisphthalocyanines under microwave irradiation. The application † Reaction procedure: A mixture of 2 (2.67 g, 0.019 mol), 3 (8 g, 0.046 mol) and K2CO3 (2 g) in 100 ml DMSO was intensively stirred for 15 h at 70 °C. After that, 2 g of K2CO3 was added and reaction was continued for 15 h at the same temperature. Reaction was monitored by TLC.Then the reaction mixture was poured into 500 ml of water, and acetic acid was added to the mixture. The residue was filtered off, flushed several times with water and recrystallised from EtOH. The reaction product was dried in air at 70 °C. 6.22 g (84%) of compound 1 was obtained. Mp 229 °C. 1H NMR (CDCl3) d: 5.51 (d, 4H, CH2, J 5 Hz), 7.4–8.1 (m, 10H, Ar). IR, nmax/cm–1: 1275 (m), 1020 (w), 3100 (w), 1250 (m), 780 (w), 1610 (w), 2224 (w). MS, m/z: 390 (M+). Found (%): C, 73.61; 73.70; H, 3.65, 3.72; N, 14.40, 14.52. Calc. for C96H56N16O8Zn2 (%): C, 73.85; H, 3.59; N, 14.35. ‡ Reaction procedure: 28 g (0.19 mol) of phthalimide was added to 32 g (0.4 mol) of NH4NO3 in 400 ml H2SO4 (d 1.84).Reaction mixture was stirred for 2 h, then poured on ice (300 g). The product was filtered off and flushed with water until neutral. The substance was dried in air at 60 °C. After crystallization from ethanol, 22.5 g (58.6%) of pure 4-nitrophthalimide were obtained. Mp 200 °C (lit.,4 mp 200–202 °C). IR, nmax/cm–1: 3340 (NH), 1710 (C=O). 2+ 2+ 21 &1 &1 2 2 &1 &1 &1 &1 6FKHPH 1+ 2 2 1+ 2 2 21 21 &21+ &21+ 21 &1 &1 L LL LLL Scheme 2 Reagents and conditions: i, conc.H2SO4, NH4NO3, 0 °C; ii, NH4OH, 20 °C; iii, POCl3, Py, 0 °C. 2.5 2.0 1.5 1.0 0.5 0.0 Absorbance 200 400 600 800 1000 l/nm Figure 1 Absorption spectrum of 4 in CH2Cl2. 352 613 680Mendeleev Communications Electronic Version, Issue 3, 2002 2 of microwave irradiation considerably simplified the synthesis, reducing the time of synthesis from several hours to several minutes. The synthesis of binuclear phthalocyanine 4 was carried out by irradiation of a homogeneous solution of compound 1 in o-DCB in the presence of two equivalents of Zn(OAc)2·2H2O in a microwave oven (Samsung, model M1915NR).The irradiation power varied from 100 to 400 W, time, from 5 to about 30 min.Experimentally, optimum conditions for the synthesis of binuclear phthalocyanine were found. On the one hand, the full conversion of bisphthalonitrile 1 took place, and, on the other hand, a smaller formation of by-products, resulting in the increased yield of the main product was observed. Thus, the optimum conditions for the microwave synthesis of 4 are as follows: irradiation power of 300W and reaction time of 15 min.The yield of phthalocyanine was 6.8%. Thus, the use of microwave irradiation decreased the reaction time and increased the yield of the binuclear phthalocyanine. This work was supported by the Russian Foundation for Basic Research (grant no. 00-03-32658). References 1 S.Marcuccio, P. Svirskaya and S. Greenberg, Can. J. Chem., 1985, 63, 3057. 2 E. Dodsworth, A. B. P. Lever and P. Seymour, J. Phys. Chem., 1985, 89, 5698. 3 H. Becker, G. Domschke, E. Fanghänel, M. Fischer, K. Gewald, R. Mayer, D. Pavel, H. Schmidt, K. Schwetlick, W. Berger, J. Faust, F. Gentz, R. Gluch, K. Müller, K. Schollberg, E. Seiler and G. Zeppenfeld, Organikum, VEB Deutscher Verlag der Wissenschaften, Berlin, 1990, vol. 2. 4 M. Bogert and L. Boroschek, J. Am. Chem. Soc., 1901, 23, 740. 5 H. Drew and D. Kelly, J. Chem. Soc., 1941, 10, 639. 6 E. G. Kogan, A. V. Ivanov, L. G. Tomilova and N. S. Zefirov, Mendeleev Commun., 2002, 54. § Reaction procedure: 55 mg of Zn(OAc)2·2H2O (0.25 mmol), 0.5 ml of isoamyl alcohol and 0.3 ml of DBU were added to a solution of 0.2 g (0.5 mmol) of compound 1 in 25 ml of o-dichlorobenzene.The mixture was boiled in an atmosphere of argon for 14 h. After completion of the reaction, the reaction mixture was filtered, and the residue on the filter was repeatedly flushed with chloroform. The filtrate was evaporated and the greasy residue was multiply flushed at first with methanol and then with chloroform. The extracts were combined and evaporated to give binuclear phthalocyanine 4 (4 mg, 1.84%). 1H NMR (CDCl3) d: 5.20 (m, 16H, OCH2), 7.2–7.8 (m, 40H, Ar). UV–VIS (CH2Cl2, lmax/nm): 352, 613, 680. MS, m/z: 1691 (M+). Found (%): C, 68.42; 68.53; H, 3.12, 3.04; N, 13.60, 13.70. Calc. for C96H56N16O8Zn2 (%): C, 68.13; H, 3.34; N, 13.24. ¶ The sample was deposited on the matrix and analysed by an ionization method during laser desorption. Intensity 1500 1000 500 1685 1688 1690 1692 1694 1696 1698 1700 m/z 1689 1690 1691 1692 1693 1694 1695 1696 1697 1698 Figure 2 The molecular ion of 4. 2 2 &1 &1 &1 &1 1 1 1 1 1 1 1 1 =Q 2 2 1 1 1 1 1 1 1 1 =Q 2 2 2 2 2 2 LY Scheme 3 Reagents and conditions: iv, DBU, isoamyl alcohol, Zn(OAc)2·2H2O, o-DCB, 14 h, 180 °C. 4 Received: 4th March 2002; Com. 02/1899

ISSN:0959-9436     

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 3, 2002 1 On the surface curvature dependence of the surface energy of a nanoparticle Anatoly I. Rusanov Mendeleev Centre, St. Petersburg State University, 199034 St. Petersburg, Russian Federation. Fax: +7 812 428 6939; e-mail: rusanov@rus.usr.pu.ru 10.1070/MC2002v012n03ABEH001593 The surface curvature dependence of pure dynamic surface energy and surface tension has been derived for a non-polar nanoparticle, the dependence containing no linear term.The effect of entropy and surface structure explains the only slight curvature dependence of real surface tension in the case of non-polar matter. The surface curvature dependence of surface tension is a central problem in the theory of capillarity. It is especially important for nanoparticles.When relating this problem to the kind of pair interaction,1 one also touches the problem of surface energy considered earlier only for a flat interface.2 One of Gibbs�f definitions of surface tension treats the quantity s as the work of formation of unit area of a new surface, say, by cutting a body. Applying this definition to the formation of a curve interface, we can imagine a ball of matter transferred from the interior of a bulk phase to a vacuum.At zero temperature, the work of transfer of the ball from a fixed position in the bulk of a condensed phase to a fixed position in a vacuum is evidently equal to the energy of cohesion of the ball with its surroundings in the bulk phase. Using the molecular pair potential (r12), the above cohesive energy U12 is given by the expression3 where r is the molecular number density in the bulk phase, r is the ball radius as the distance from the ball centre to the centres of its surface molecules and d is the minimum intermolecular distance (the molecular size) in the bulk phase (Figure 1).For the particular case of dispersion forces [(r12) = �]lr12 6 ] and choosing d as unit length, equation (1) yields where l is the London constant and R o r/d + 1/2 is the dimensionless radius of the equimolecular surface (Figure 1).By dividing (2) by the surface area 4ƒÎR2, we obtain the expression for the cohesive energy u12 of a curved interface per unit area Passing to the limit RR\, equation (3) changes to the wellknown expression for the dispersion-forces cohesive energy of two half-spaces separated by a flat slit of width d (d = 1 this time):4 Since we integrated from a smallest distance, the question arises about the role of repulsion energy.Using the Lennard�] Jones potential (r12) = �]lr 6 12 + lr12 12, we can calculate the contribution of repulsion energy just in the above way. This contribution depends on R, but is small at large R.In particular, when taking the repulsion energy into account, (4) is replaced by which shows the repulsion energy to amount only about 3% in the limit RR\. The opposite limit R R 1/2 (when the ball includes only one molecule) requires a separate calculation in the point-force approach since equation (3), which is based on the integration over the ball volume, yields u12 = 0 when the ball degenerates into a point.The result is easily obtained as or, using the Lennard�]Jones potential, where the contribution of repulsion is shown to amount 1/3 of that of attraction. In the dimensionless units used, the volume of a spherical molecule is ƒÎ/6 and its surface area is ƒÎ, so that the cohesive energy per unit surface area for a single molecule is Assuming the structure of matter unchanged (as a consequence, e.g., of non-compressibility and zero temperature), the work of disjoining of the ball and its surroundings is just equal to the reverse cohesive energy.Then surface energy e (coinciding with surface tension at zero temperature) is defined as half of reverse cohesive energy per unit surface area. Thus, we have from (3) (neglecting the contribution of repulsion) which exhibits a monotonic increase of the surface energy of a nanoparticle with the particle size.Expanding (9) into a series with respect to 1/R (b = ln 2 + 1/2 �â 1.193) we discover the absence of a linear term typical of the curvature dependence of surface tension.5,6 This effect is predictable. The cohesion energy equally belongs to convex and concave surfaces in touch with each other if they possess identical structures (coinciding with the structure of the bulk phase). As a result, the surface energies of both of the surfaces are the same and, therefore, are independent of the curvature sign, which is possible only in the absence of a linear term from (10).Thus, we can conclude that a linear term can appear due to the effects of entropy (at temperatures above zero) and specific surface structure (different for a convex surface and a concave one) as a consequence of non-zero compressibility.In two opposite limiting cases R = \ and R = 1/2, we have from (5) and (8) (exact results accounting for repulsion) for a macroscopic body and a single molecule in a vacuum, respectively. From (11) and (12) we obtain The result is not surprising: it is much more difficult to extract a molecule from the bulk than to transfer the molecule to the surface.The particular value of e1/e\ depends on the value of r (1 �’ r < 2), which, in turn, depends on the type of packing; U12 = 4ƒÎ2r2 ydy (r12)r12[r2 �] (y �] r12)2]dr12 , �ç r + d \ �ç y �] r y + r (1) U12 = �] 4R2 �] 4ln(2R) �] , ƒÎ2r2l 12 1 4R2 (2) u12(R) = �] 1�] �] .ƒÎr2l 12 1 16R4 (3) ln(2R) R2 u12(\) = �] . ƒÎr2l 12 (4) u12(\) = �] , 29ƒÎr2l 360 (5) U12(1/2) = 4ƒÎr (r12)r 2 12 dr12 �ç1 \ (6) U12(1/2) = 4ƒÎrl �] = �] ƒÎrl, 1 9 (7) 1 3 8 9 u12(1/2) = U12(1/2)/ƒÎ = �] rl. (8) 8 9 e(R) = 1�] �] , ƒÎr2l 24 1 16R4 (9) ln(2R) R2 e(R) = 1 �] + ... , ƒÎr2l 24 (10) b R2 e\ = �] ; 29ƒÎr2l 720 (11) e1 = �] rl (12) 4 9 e1/e\ = 4�~720/29�~9�~ƒÎr �â 3.5/r.(13)Mendeleev Communications Electronic Version, Issue 3, 2002 2 r = 1 and e1/e¡Í ¡í 3.5 for the cubic packing. The most compact packing of hard spheres requires r = 1.4 and e1/e¡Í ¡í 2.5. The surface energy and surface tension coincide at zero temperature. However, they can be different at room temperature. The surface tension is equal to the specific free surface energy of pure liquids.The common mechanical definition of surface tension is scarcely applicable to a free single molecule, but we can operate with free surface energy s to characterise this case. Using the Dupre rule we can easily calculate the specific free surface energy s of a single molecule from the work w of transfer of the molecule from a fixed position in a condensed phase to a fixed position in a vacuum (A is the surface area). Since the free surface energy of a molecule inside a bulk phase is zero, the specific free surface energy of the molecule in a vacuum can be estimated as In turn, the work of transfer of a molecule from a condensed phase ¥á to a gaseous phase ¥â can be found from the standard relationship where k is Boltzmann¡�s constant, T is temperature, and the equilibrium phase concentration ratio stands under the logarithm sign.Here, we present the calculation for carbon tetrachloride at 20 ¡ÆC. The reference data for CCl4 are as follows: molecular mass M = 153.81, density d = 1595 kg m.3, surface tension s = = 25.68 mJ m.2, and vapour pressure p¥â = 91.28 Torr.7 Assuming the ideal behaviour of a gaseous phase, we find r¥â = = p¥â/kT = 3.01¡¿1024 m.3.Further calculations gave: r¥á = NA(d/M) = = 6.25¡¿1027 m.3 (NA is Avogadro¡�s number) and r¥á/r¥â = 2075. Equation (16) yields w = 3.09¡¿10.20 J. The volume per molecule of CCl4 in the liquid phase is v¥á = = 1/r¥á = 160.1¡¿10.30 m3. Choosing the location of thethe same volume in a vacuum, we calculate the molecular diameter as d = (6v¥á/¥�)1/3 = 6.76¡¿10.10 m.Correspondingly, the dividing surface area is A1 = ¥�d2 = 142.6¡¿10.20 m2 and the specific free surface energy (surface tension) attributed to this dividing surface is s1 = w/A1 = 21.66 mJ m.2 ¡í 0.84s. In contrast with surface energy, the free surface energy of a single molecule is relatively close to the macroscopic surface tension.This quite different behaviour of surface energy and free surface energy gives evidence for a great role of entropy. The extraction of a molecule from the depth of a bulk phase requires much more energy but is accompanied by a much greater release of entropy as compared with the transfer of the molecule to the surface.The compensation effect of entropy explains the slight dependence of the surface tension of non-polar liquids on the surface curvature. This work was supported by the Russian Foundation for Basic Research (grant no. 98-03-32009a). References 1 R.Tsekov, K.W.Stockelhuber and B. V. Toshev, Langmuir, 2000, 16, 3502. 2 A. I. Rusanov, J. Colloid Interface Sci., 1982, 90, 143. 3 A. I. Rusanov, Micellization in Surfactant Solutions, Chemistry Reviews, ed. M. E. Vol¡�pin, Harwood Academic Publ., 1997, vol. 22, part 1. 4 J. Mahanty and B. W. Ninham, Dispersion Forces, Academic Press, London, 1976. 5 J. C. Melrose, Ind. Eng. Chem., 1968, 60 (3), 53. 6 A. I. Rusanov, Phasengleichgewichte und Grenzflaechenerscheinungen, Akademie-Verlag, Berlin, 1978. 7 Spravochnik khimika (Reference Book of a Chemist), Gosudarstvennoe Nauchno-tekhnicheskoe Izdatel¡�stvo Khimicheskoi Literatury, Leningrad, 1963, vol. 1. R r d Figure 1 The interaction of the ball of matter with its surroundings. w = A.s, (14) s = w/A. (15) w = kTln(r¥á/r¥â), (16) Received: 19th April 2002; Com.

ISSN:0959-9436     

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 3, 2002 1 Reactions of N,N-bis(siloxy)enamines with trimethylsilyl cyanide: aliphatic nitro compounds as convenient precursors of 5-aminoisoxazoles Aleksei V. Lesiv, Sema L. Ioffe,* Yurii A. Strelenko, Igor’ V. Bliznets and Vladimir A. Tartakovsky N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.Fax: +7 095 135 5328; e-mail: iof@cacr.ioc.ac.ru 10.1070/MC2002v012n03ABEH001585 A convenient procedure was developed for the synthesis of 5-aminoisoxazoles by the consecutive double silylation and cyanation of aliphatic nitro compounds. N,N-Bis(siloxy)enamines (BENA) 1,1,2 double silylation products of available aliphatic nitro compounds, behave as â-Celectrophiles toward various C- and N-centred nucleophiles3 (the anions of â-dicarbonyl and nitro compounds, silyl nitronates, primary or secondary amines, and silyl derivatives of N-nitroamines or azoles).It was assumed3,4 that conjugated nitrosoalkenes that resulted from BENA under the action of nucleophiles rather than BENA are actual intermediates in these reactions. In this context, it is of interest to use the cyanide ion as a nucleophile in such reactions because the corresponding á-cyano oximes (or their silyl derivatives), the probable primary products of its C,C-cross-coupling reactions with BENA, were not described in the literature, although they might be usable in organic synthesis.The aim of this work was to study the interaction of the cyanide ion with BENA 1.We found that BENA 1b reacted with potassium cyanide in the presence of dibenzo-18-crown-6 afforded a difficult-toseparate mixture of unidentified products. At the same time, trimethylsilyl cyanide (TMSCN) smoothly reacts with BENA 1 over a wide range of conditions to give previously unknown trimethylsilyl derivatives of cyanoximes 2. It is likely that it is optimum to use solutions of equimolar amounts of reactants in CH2Cl2 in the presence of 10 mol% Et3N (Scheme 1 and Table 1).† It is well known6 that Et3N catalysis is required for the C,C-cross-coupling of silyl nitronates with BENA.However, the reaction BENA + TMSCN can also be performed without Et3N. In this case, the reaction occurs without a solvent at 20 °C for several days, and the yields of target products 2 are close to those given in Table 1.‡ Scheme 2 illustrates a conceivable reaction mechanism. We believe that Et3N, reacting with TMSCN, generates conjugated nitrosoalkene A from BENA 1.This active intermediate further reacts with TMSCN to give a mixture of syn- and anti-isomers of the silyl derivatives of cyano-substituted oximes 2 and 2' (see also Scheme 1).TMSCN may participate in this process in a tautomeric isonitrile form.7 It was previously noted8 that the cyanide ion reacts with nitrosoalkenes A to form 5-aminoisoxazoles 4. In the absence of Et3N, intermediate A was generated with the use of TMSCN, however, at a much lower rate. Scheme 1 Reagents and conditions: i, CH2Cl2, Et3N (cat.), 20–40 °C; ii, MeOH, Et3N (cat.), 20 °C.N(OSiMe 3)2 R1 R2 + Me3SiCN N R1 NC R2 Me3SiO i N R1 NC R2 OSiMe3 1a–g 2a– g 2'a–g 42–79% ii N R1 NC R2 HO N R1 NC R2 OH 3a–g 3'a–g N O R2 R1 NH2 4a–g 36–79% † General procedure for the synthesis of silyl derivatives 2a–e. All reactions with BENA were performed in specially dried solvents in a dry argon atmosphere. Et3N (0.5 mmol, 0.07 ml) and then BENA 1a–e (5 mmol) were added to TMSCN5 (5 mmol, 0.67 ml) in freshly distilled CH2Cl2 (7.5 ml) at 20 °C with intense stirring.After an induction period (from a few seconds to 45 min), the reaction mixture warmed up to boiling; it was allowed to stand for 1.5 h, volatile components were distilled at 40 °C/20 Torr, and the residue was fractionated in a vacuum to obtain silyl derivatives 2a–e (the yields are given in Table 1).NMR spectra were measured on a Bruker AM-300 spectrometer (operating frequency of 300.3 MHz for 1H, 75.47 MHz for 13C and 59.63 MHz for 29Si, INEPT); TMS was used as an internal standard; CDCl3 was a solvent, unless otherwise specified. 3-(Trimethylsilyloximino)propionitrile (2a + 2'a; E/Z = 1:2.2): yield 49%, bp 35–36 °C/0.35 Torr. E: 1HNMR, d: 0.19 (s, 9H, SiMe3), 3.28 (d, 2H, CH2, 3J 5.1 Hz), 7.41 (t, 1H, CH, 3J 5.1 Hz); 13C NMR, d: –0.9 (SiMe3), 19.0 (CH2), 114.9 (CN), 143.8 (CH); 29Si NMR, d: 28.08. Z: 1H NMR, d: 0.19 (s, 9H, SiMe3), 3.41 (d, 2H, CH2, 3J 4.4 Hz), 6.96 (t, 1H, CH, 3J 4.4 Hz); 13C NMR, d: –0.9 (SiMe3), 14.8 (CH2), 115.6 (CN), 142.5 (CH); 29Si NMR, d: 28.72. 3-(Trimethylsilyloximino)butyronitrile (2b + 2'b; E/Z = 1.2:1): yield 79%, bp 28–29 °C/0.35 Torr.E: 1H NMR, d: 0.19 (s, 9H, SiMe3), 2.10 (s, 3H, Me), 3.38 (s, 2H, CH2); 13C NMR, d: –0.8 (SiMe3), 13.5 (Me), 24.7 (CH2), 115.5 (CN), 151.6 (C=N); 29Si NMR, d: 26.65. Z: 1H NMR, d: 0.19 (s, 9H, SiMe3), 1.98 (s, 3H, Me), 3.50 (s, 2H, CH2); 13C NMR, d: –0.9 (SiMe3), 17.8 (Me), 19.3 (CH2), 115.6 (CN), 149.7 (C=N); 29Si NMR, d: 26.80. 2-Methyl-3-(trimethylsilyloximino)propionitrile (2c + 2'c; E/Z = 4:3): yield 70%, bp 38 °C/0.4 Torr.E: 1H NMR, d: 0.20 (s, 9H, SiMe3), 1.48 (d, 3H, Me, 3J 7.3 Hz), 3.53 (m, 1H, CHMe), 7.41 (d, 1H, HC=N, 3J 5.1 Hz); 13C NMR, d: –0.9 (SiMe3), 16.4 (Me), 26.6 (CHMe), 118.7 (CN), 149.1 (C=N). Z: 1H NMR, d: 0.21 (s, 9H, SiMe3), 1.43 (d, 3H, Me, 3J 7.3 Hz), 4.23 (m, 1H, CHMe), 6.88 (d, 1H, HC=N, 3J 5.2 Hz). 13C NMR, d: –0.9 (SiMe3), 15.6 (Me), 21.7 (CHMe), 119.1 (CN), 148.3 (C=N). Methyl 5-cyano-4-(trimethylsilyloxy)pentanoate (2d + 2'd; E/Z = 1:3): yield 61%, bp 84–88 °C/0.20 Torr. E: 1H NMR, d: 0.12 (s, 9H, SiMe3), 2.58, 2.69 (m, 4H, CH2CH2), 3.37 (s, 2H, CH2), 3.62 (s, 3H, OMe); 13C NMR: –1.0 (SiMe3), 23.4 (CH2CH2NOSi), 23.8 (CH2CN), 29.8 (CH2CO2), 51.7 (Me), 115.3 (CN), 154.0 (C=N), 172.7 (CO).Z: 1H NMR, d: 0.14 (s, 9H, SiMe3), 2.58, 2.69 (m, 4H, CH2CH2), 3.44 (s, 2H, CH2), 3.62 (s, 3H, OMe); 13C NMR, d: –0.9 (SiMe3), 17.4 (CH2CN), 28.6 (CH2CH2CNOSi), 29.6 (CH2CO2), 51.5 (Me), 115.3 (CN), 150.7 (C=N), 172.4 (CO). 3-Phenyl-3-(trimethylsilyloximino)propionitrile (2e): yield 72%, bp 92 °C/ 0.50 Torr. E: 1H NMR, d: 0.35 (s, 9H, SiMe3), 3.87 (s, 2H, CH2), 7.45, 7.70 (m, 5H, Ph); 13C NMR: –0.6 (SiMe3), 14.8 (CH2), 115.3 (CN), 126.2, 128.7, 130.1, 133.5 (Ph), 150.9 (C=N).‡ TMSCN (2 mmol, 0.27 ml) was added to freshly distilled enamine 1b (2 mmol, 0.46 g) with stirring at room temperature, the reaction mixture was allowed to stand at 20 °C for 48 h, volatile components were distilled at 20 °C/0.1 Torr, and an aliquot portion of CH2Cl2 was added as an internal standard to the residue.The yield of mixture of 2b + 2'b was 82%, molar ratio 2b:2'b ~ 1:1.2.Mendeleev Communications Electronic Version, Issue 3, 2002 2 The role of CH2Cl2 is reduced to the dissolution of reactants and to the control of reaction temperature by heat removal due to the boiling of the solvent. According to NMR data, derivatives 2a.d are mixtures of Zand E-isomers (2 and 2', respectively, in Scheme 1 and Table 1).Compounds 2e.g were detected as individual isomers with the Z-configuration of CN and OSiMe3 groups. It is likely that the Z/E ratios given in Table 1 are thermodynamic values because they remained unchanged after the vacuum distillation of these products. Note that compounds 2a.e with > 90% purity (NMR data) can be isolated by fractionation (the synthesis of 2f,g will be considered below).The desilylation of derivatives 2a.g by the action of methanol with Et3N added afforded 5-aminoisoxazoles 4a.g in place of corresponding free oximes 3a.g (Scheme 1, Table 1).¡× Evidently, only isomers 3, in which CN and OH groups are close to each other, undergo cyclisation. The so-called mild methanolysis of oxime derivatives 2c + 2'c resulted in the formation of corresponding isoxazole 4c only from isomer 2c, whereas isomer 2'c was converted into the E-isomer of oxime 3'c.Isomer 3'c in CDCl3 was also very slowly isomerised to isoxazole 4c in a spectrometer ampoule (Scheme 3). It is believed that the rate of this cyclisation corresponds to the rate of the equilibration 3c 3'c.¢Ò In contrast to the anions of aliphatic nitro compounds and silyl nitronates, TMSCN readily reacts with both terminal and internal BENA.All of these reactions are chemoselective; that is, the corresponding isonitrile derivatives were not detected. Let us consider the reactions of TMSCN with BENA 1g,f, containing a CO2Alk group at the ¥á-position, in more detail (Schemes 4 and 5).The cross-coupling of TMSCN with BENA 1f is accompanied by a considerable contribution of the rearrangement of BENA 1f into compound 5 (~15%).13 For this reason, TMS derivative 2f cannot be isolated from the reaction mixture (Scheme 5).¢Ó¢Ó The interaction of internal BENA 1g with TMSCN is more complicated (Scheme 5). Under standard reaction conditions, only compound 6 was detected, which was transformed by desilylation into enoxime 7, which is much more stable.However, the NMR monitoring allowed us to detect the initial formation of cyanoxime 2g, which afforded aminoisoxazole 4g as a result of rapid desilylation (Table 1). Compound 2g in CH2Cl2 was gradually converted into silyl enoxime derivative 6 (Scheme 5). The reaction 2g ¢ç 6 can include the consecutive Table 1 Product yields in the test reactions.BENA R1 R2 Yield of 2 + 2' (%) 2:2' Yield of 4 (%) on a BENA basis 1a H H 49 2.2:1 49 1b Me H 79 1:1.2 79 1c H Me70 3:4 70 1d CH2CH2CO2Me H 61 3:1 61 1e Ph H 72 only 2e 72 1f CO2Et H 42 only 2f 36 1g CO2Me Me 62a aWith respect to an internal standard. obly 2g 54 N(OSiMe3)2 R1 R2 1 CN. . (Me3Si)2O N R1 R2 A O Me3SiCN + NEt3 CN.+ Me3SiN+Et3 Me3SiC¡ÕN Me3SiN=C (ref. 7) N R1 R2 2 + 2' NC Me3SiO Scheme 2 NC N Me3SiO 2c + 2'c MeOH, 20 ¡ÆC, 3 h N O NH2 4c NC N 3'c OH CDCl3, 1 week Scheme 3 ¡× General preparation procedure for aminooximes 4a.e. Distilled compound 2 (3 mmol) was dissolved in methanol (5 ml), and Et3N (0.1 ml) was added; after 24 h, the solvent was evaporated at 50 ¡ÆC/ 20 Torr, and isoxazole 4 of > 90% purity (NMR data) was obtained. 5-Isoxazolamine 4a (lit.9): yield 49%, mp 72.73 ¡ÆC. 1H NMR, d: 4.9 (br. s, 2H, NH2), 5.07 (d, 1H, CHCNH2, 3J 1.5 Hz), 7.91 (d, 1H, CHCN, 3J 1.5 Hz); 13C NMR, d: 78.8 (CHCHC), 151.9 (C=N), 168.6 (CNH2). Found (%): C, 42.82; H, 4.82; N, 33.21. Calc. for C3H4N2O (%): C, 42.86; H, 4.80; N, 33.32. 3-Methyl-5-isoxazolamine 4b (lit.10): yield 79%, mp 82.84 ¡ÆC. 1HNMR, d: 2.12 (s, 3H, Me), 4.5 (br. s, 2H, NH2), 4.94 (s, 1H, CH); 13C NMR, d: 11.7 (Me), 80.6 (CH), 161.6 (C=N), 168.4 (CNH2). Found (%): C, 48.94; H, 6.16; N, 28.63. Calc. for C4H6N2O (%): C, 48.97; H, 6.16; N, 28.55. 4-Methyl-5-isoxazolyloxazole 4c (lit.11): yield 70%, oil. 1H NMR, d: 1.68 (s, 3H, Me), 4.7 (br. s, 2H, NH2), 7.72 (s, 1H, CH); 13C NMR, d: 6.0 (Me), 87.4 (CMe), 153.2 (CH), 165.7 (CNH2).Found (%): C, 49.20; H, 6.03; N, 28.31. Calc. for C4H6N2O (%): C, 48.97; H, 6.16; N, 28.55. Methyl 3-(5-amino-3-isoxazolyl)propionate 4d: yield 61%, mp 65.67 ¡ÆC. 1H NMR, d: 2.64, 2.82 (t, 4H, CH2CH2, 3J 7.4 Hz), 3.69 (s, 3H, Me), 4.7 (br. s, 2H, NH2), 4.98 (s, 1H, CH); 13C NMR, d: 22.6 (CH2CH2CO2), 29.1 (CH2CO2), 51.4 (Me), 83.7 (CH), 159.8 (C=N), 167.1 (CNH2), 172.9 (CO).Found (%): C, 49.24; H, 5.86; N, 16.21. Calc. for C7H10N2O3 (%): C, 49.41; H, 5.92; N, 16.46. 3-Phenyl-5-isoxazolamine 4e (lit.12): yield 72%, mp 104.108 ¡ÆC. 1H NMR, d: 4.8 (br. s, 2H, NH2), 5.41 (s, 3H, CH), 7.43 (m, 2H, Ph), 7.62 (m, 1H, Ph), 7.71 (m, 2H, Ph); 13C NMR, d: 78.26 (CH), 126.16, 126.79, 128.83, 129.87 (Ph), 163.94 (C=N), 169.25 (CNH2).Found (%): C, 67.38; H, 5.18; N, 17.57. Calc. for C9H8N2O (%): C, 67.49; H, 5.03; N, 17.49. ¢Ò Distilled derivative 2c (1 mmol, 0.17 g) was dissolved in methanol (1 ml); after 3 h, the mixture was evaporated at 20 ¡ÆC/15 Torr. According to 1H NMR data, the residue contained aminoisoxazole 4c (67%) and E-2-methyl-3-oximinopropionitrile 3'c (33%), 1H NMR, d: 1.49 (d, 3H, Me, 3J 7.2 Hz), 3.53 (m, 1H, CHMe), 7.37 (d, 1H, CH=N, 3J 5.9 Hz), 9.12 (br.s, 1H, OH). 13C NMR, d: 16.5 (Me), 26.6 (CHMe), 119.2 (CN), 145.2 (C=N). After a week, oxime 3'c in an ampoule was completely converted into aminoisoxazole 4c. ¢Ó¢Ó Et3N (0.5 mmol, 0.7 ml) was added to TMSCN (5 mmol, 0.67 ml) in CH2Cl2 (7.5 ml) at 20 ¡ÆC; next, a solution of BENA 1f (5 mmol, 1.46 g) in CH2Cl2 (5 ml) was added for 5 min with intense stirring; the reaction mixture temperature was kept at 20.30 ¡ÆC.The reaction exhibited an induction period. The mixture was allowed to stand for 1 h; volatile components were distilled at 40 ¡ÆC/20 Torr, and the residue was fractionated at 70.80 ¡ÆC/0.4 Torr. According to NMR data, the distillate contained compounds 2f (42%, 0.48 g) and 5 (15%, 0.2 g).E-Ethyl 3-cyano-2-(trimethylsilyloximino)propionate 2f: 1H NMR, d: 0.29 (s, 9H, SiMe3), 1.31 (t, 3H, Me, 3J 7.4 Hz), 3.60 (s, 2H, CH2CN), 4.29 (q, 2H, CH2Me, 3J 7.4 Hz). 13C NMR, d: .0.9 (SiMe3), 13.8 (Me), 14.0 (CH2CN), 62.4 (CH2Me), 114.1 (CN), 145.9 (C=N), 161.8 (CO). Ethyl 3-trimethylsiloxy-2-(trimethylsilyloximino)propionate 5 (lit.2): 1H NMR, d: 0.09 (s, 9H, CH2OSiMe3), 0.21 (s, 9H, NOSiMe3), 1.29 (t, 3H, Me, 3J 7.3 Hz), 4.25 (q, 2H, CH2Me, 3J 7.3 Hz), 4.52 (s, 2H, CH2OSi). 13C NMR, d: .0.9 (CH2OSiMe3), .0.5 (NOSiMe3), 14.1 (Me), 53.8 (CH2C=N), 61.3 (CH2Me), 156.5 (C=N), 163.4 (CO). The distillate was dissolved in methanol (5 ml) with an additive of Et3N (0.1 ml), the mixture was allowed to stand for 6 h at 20 ¡ÆC and then evaporated at 50 ¡ÆC/20 Torr.Oily crystals were obtained. Ethyl 5-amino-3-isoxazolcarboxylate 4f: (36%, 0.28 g), mp 96.98 ¡ÆC (from CCl4). 1H NMR, (C2D5OD) d: 1.40 (t, 3H, Me, 3J 7.4 Hz), 4.37 (q, 2H, CH2, 3J 7.4 Hz), 5.23 (s, 2H, NH2), 5.41 (s, 1H, CH). 13C NMR, d: 15.2 (Me), 63.1 (CH2), 79.8 (CH), 158.5 (CN), 162.3 (CO), 174.0 (CNH2). Found (%): C, 45.91; H, 5.07; N, 17.68. Calc. for C6H8N2O3 (%): C, 46.15; H, 5.16; N, 17.94.Mendeleev Communications Electronic Version, Issue 3, 2002 3 1,5-O,O migration of the Me3Si group to the oxygen atom of the CO2Me unit, the subsequent elimination of Me3SiCN, the 1,5-CO proton shift14 in resulting intermediate A' and, finally, the silylation of enoxime 7 with the use of Me3SiCN/Et3N.The direct elimination of HCN from oxime 2g seems to be less probable, although it cannot be completely excluded (Scheme 5).Because of this, the general procedure used for the synthesis of isoxazoles 4a–e was modified for preparing isoxazole 4g.‡‡ The structures of compounds were supported by elemental analysis and NMR spectroscopy. The configuration of the oxyimino group in products 2a–d, 2'a–d, 3'c, 6 and 7 was determined based on previously published rules,2,15 as illustrated in Figure 1.The configuration of the oxyimino group in products 2e–g, which have only one stereoisomer, was found by comparing the chemical shifts of their characteristic fragments with the chemical shifts16 of analogous fragments in isomers 2a–d (Figure 1). Thus, we proposed a convenient method for the synthesis of 5-aminoisoxazoles 4, which may exhibit biological activity,17 using the simplest aliphatic compounds as starting substrates.This work was supported by the Russian Foundation for Basic Research (grant no. 99-03-32015) and the ‘Integratsiya’ Special Federal Programme (project no. A0082). We are grateful to ChemBridge Corporation for providing us with chemicals for this study. References 1 A. D.Dilman, A. A. Tishkov, I. M. Lyapkalo, S. L. Ioffe, Yu. A. Strelenko and V. A. Tartakovsky, Synthesis, 1998, 181. 2 A. D. Dilman, A. A. Tishkov, I. M. Lyapkalo, S. L. Ioffe, V. V. Kachala, Yu. A. Strelenko and V. A. Tartakovsky, J. Chem. Soc., Perkin Trans. 1, 2000, 2926. 3 V. A. Tartakovsky, S. L. Ioffe, A. D. Dilman and A. A. Tishkov, Izv. Akad. Nauk, Ser. Khim., 2001, 1850 (Russ. Chem.Bull., Int Ed., 2001, 50, 1936). 4 A. D. Dilman, I. M. Lyapkalo, S. L. Ioffe, Yu. A. Strelenko and V. A. Tartakovsky, Synthesis, 1999, 1767. 5 J. K. Rasmussen and S. M. Heilmann, Synthesis, 1979, 523. 6 A. D. Dilman, A. A. Tishkov, I. M. Lyapkalo, S. L. Ioffe, Yu. A. Strelenko and V. A. Tartakovsky, Izv. Akad. Nauk, Ser. Khim., 2000, 876 (Russ. Chem. Bull., Int. Ed., 2000, 49, 874). 7 J.A. Seckar and J. S. Thayer, Inorg. Chem., 1976, 15, 501. 8 M. Dines and M. L. Scheinbaum, Tetrahedron Lett., 1969, 54, 4817. 9 A.Quilico, Gazz. Chim. Ital., 1931, 61, 759. 10 P. S. Burns, J. Prakt. Chem. [2], 1893, 47, 105. 11 K. Matsumura, T. Saraie, V. Kawano, N. Hashimoto and K. Morita, J. Takeda Res. Lab., 1971, 30, 486. 12 L. Almirante, A. Biance and V. Zambni, Ann.Chim. (Rome), 1956, 46, 623. 13 H. Feger and G. Simchen, Liebigs Ann. Chem., 1986, 428. 14 I. M. Lyapkalo and S. L. Ioffe, Usp. Khim., 1998, 67, 523 (Russ. Chem. Rev., 1998, 67, 467). 15 L. M. Makarenkova, I. V. Bliznets, S. L. Ioffe, Yu. A. Strelenko and V. A. Tartakovsky, Izv. Akad. Nauk, Ser. Khim., 2000, 1265 (Russ. Chem. Bull., Int. Ed., 2000, 49, 1261). 16 M. Hesse, H.Meier and B. Zeeh, Spektroskopische Methoden in der Organischen Chemie, Georg Thieme Verlag, Stuttgart, 1995, p. 200. N(OSiMe3)2 CO2Et + Me3SiCN CH2Cl2/Et3N (cat.) 20–30 °C N Me3SiO CO2Et NC 1f 2f NOSiMe3 CO2Et Me3SiO 5 (15%) MeOH N O NH2 4f EtO2C Scheme 4 N O SiMe3 O MeO NC Me3Si NC O OMe NO – Me3SiCN N CO2Me A' O N CO2Me 7 OH N CO2Me 6 OSiMe3 Et3N – HCN Me3SiCN/NEt3 – HCN Scheme 5 2g N C HO Cá N C OH Cá ' d 13Cá < d 13Cá N C HO H N C OH H' d 1H > d 1H' ' N C HO C N C OH C H H' d 1H > d 1H' Figure 1 ‡‡BENA 1g (5 mmol, 1.46 g) was added to a mixture of TMSCN (5 mmol, 0.67 ml) and Et3N (0.5 mmol, 0.07 ml) for 10 min with intense stirring (the mixture warmed up in the course of adding BENA; however, the temperature was kept within a range of 30–40 °C).E-Methyl 2-(trimethylsilyloximino)- 3-cyanobutyrate 2g was detected by NMR spectroscopy (62% yield). 1H NMR, d: 0.31 (s, 9H, SiMe3), 1.53 (d, 3H, CHMe, 3J 7.4 Hz), 3.86 (s, 3H, OMe), 4.40 (q, 1H, CHMe, 3J 7.4 Hz). 13CNMR, d: –0.9 (SiMe3), 15.5 (Me), 22.1 (CH), 52.9 (OMe), 118.3 (CN), 150.2 (C=N), 162.2 (CO). After 10 min, methanol (5 ml) was added, and the mixture was allowed to stand for 6 h.Volatile components were distilled at 50 °C/20 Torr, and oily crystals were obtained. Methyl 5-amino-4-methyl-3-isoxazolcarboxylate 4g: yield 54%, 0.42 g; mp 112–114 °C (from CCl4). 1H NMR, d: 1.92 (s, 3H, CMe), 3.76 (s, 3H, OMe), 5.26 (br. s, 2H, NH2). 13C NMR, d: 6.2 (CMe), 52.7 (OMe), 89.2 (CMe), 156.2 (C=N), 162.6 (CO), 169.3 (CNH2). BSENA 1g (2 mmol, 0.58 g) was added to a solution of TMSCN (2 mmol, 0.27 ml) and NEt3 (0.5 mmol, 0.07 ml) in 3 ml of CH2Cl2 at 20 °C.The mixture was allowed to stand for 24 h and then distilled at 51 °C/0.9 Torr. The yield of enoxime 6 was 47% (0.19 g). Compound 6 is very unstable, and it completely decomposed at 20 °C in 1 h. Therefore, methanol (2 ml) was immediately added to the distillate, and the solution was chromatographed on silica gel (eluent: ethyl acetate–light petroleum, 1:1).Rf 0.68 (Z-isomer) or 0.44 (E-isomer). Compound 7: Z: 13% (0.034 g), E: 28% (0.072 g). Methyl 2-(trimethylsilyloximino)but-3-enoate (6 + 6'; E/Z = 7:4): E: 1H NMR, d: 0.25 (s, 9H, SiMe3), 3.84 (s, 3H, OMe), 5.67 (dd, 1H, CH2, 3J 11.7 Hz, 2J 2.1 Hz), 6.13 (dd, 1H, CH2, 3J 17.7 Hz, 2J 2.1 Hz), 6.94 (dd, 1H, CH, 3J 17.7 Hz, 3J 11.7 Hz); 13C NMR, d: –0.8 (SiMe3), 52.3 (OMe), 122.6 (CH2), 128.8 (CH), 152.4 (C=N), 163.4 (CO). Z: 1HNMR, d: 0.25 (s, 9H, SiMe3), 3.88 (s, 3H, OMe), 5.43 (d, 1H, CH2, 3J 17.7 Hz), 5.58 (d, 1H, CH2, 3J 11.2 Hz), 6.46 (dd, 1H, CH, 3J 17.7 Hz, 3J 11.2 Hz); 13C NMR, d: –0.9 (SiMe3), 52.3 (OMe), 122.3 (CH2), 125.4 (CH), 152.4 (C=N), 163.4 (CO). Methyl 2-oximinobut-3-enoate (7, 7'): E: 1H NMR, d: 3.84 (s, 3H, OMe), 5.78 (dd, 1H, CH2, 3J 11.8 Hz, 2J 2.0 Hz), 6.38 (dd, 1H, CH2, 3J 17.7 Hz, 2J 2.0 Hz), 6.82 (dd, 1H, CH, 3J 17.7 Hz, 3J 11.5 Hz), 10.1 (br. s, 1H, OH); 13C NMR, d: 52.6 (OMe), 121.8 (CH2), 127.2 (CH), 146.5 (C=N), 163.1 (CO). Z: 1H NMR, d: 3.91 (s, 3H, OMe) 5.54 (d, 1H, CH2, 3J 17.7 Hz), 5.63 (d, 1H, CH2, 3J 11.2 Hz), 6.46 (dd, 1H, CH, 3J 17.7 Hz, 3J 11.2 Hz), 9.1 (br. s, 1H, OH); 13C NMR, d: 52.4 (OMe), 122.6 (CH2), 128.3 (CH), 152.0 (C=N), 163.1 (CO).Mendeleev Communications Electronic Version, Issue 3, 2002 4 17 P. D. Stein, D. M. Floyd, S. Bisaha, J. Dickey, R. N. Girotra, J. Z. Gougoutas, M. Kozlowski, V. G. Lee, E. C.-K. Liu, M. F. Malley, D. McMullen, C. Mitchell, S. Moreland, N. Murugesan, R. Serafino, M. L. Webb, R. Zhang and J. T. Hunt, J. Med. Chem., 1995, 38, 1344. Received: 26th March 2002; Com. 02/1911

ISSN:0959-9436     

出版商:RSC    

年代:2002

数据来源: RSC