摘要:

O C H N H H O C H N H H TS1 TS2 J. CHEM. RESEARCH (S), 1998 1 J. Chem. Research (S), 1998, 1 J. Chem. Research (M), 1998, 0242–0264 Prediction of the Molecular Structure, Internal Rotational Barriers and Vibrational Frequencies of Formamide by Nonlocal Density Functional Theory Frank U. Axe,a Venkatesan Renugopalakrishnan*a,b,c and Arnold T. Haglera aBiosym/MSI, Inc., 9685 Scranton Road, San Diego, CA 92121, USA bHarvard Medical School, Boston, MA 02115, USA cInstituto de Quimica, Universidad Nacional Autonoma de Mexico, Circuito Exterior, Ciudad Universitaria, Coyoacan, 0451 Mexico DF, Mexico A state-of-the-art non-local density functional study of formamide is reported and compared with experimental molecular structure, internal rotational barriers and vibrational frequencies. Formamide is the simplest molecule containing a peptide moiety and hence has been the focus of numerous experimental20 and theoretical studies.39 Many of these studies were carried out on formamide with a view to understand the molecular structure and energetics of the peptide moiety, which is of fundamental importance to protein structure.The calculation of the energy surface for even the simplest peptide is a challenging task. Therefore continuing refinement of the force fields for proteins depends on first-principle quantum chemical methods. Density functional theory (DFT), originally developed for problems in solid state physics, is a first-principle quantum chemical method6 which includes a treatment of electron correlation and has also been demonstrated to be of comparable accuracy and computational efficiency7 to post-Hartree–Fock methods.The precise extent of the importance of electron correlation in the calculation of conformational energies of peptides remains unknown at the present time, although its importance has been demonstrated by previous studies.10 DFT is better suited for application to large molecules of biological interest.11 Previously, DFT calculations were performed with local density functionals (LDF) for exchange and correlation.6 However, more recently DFT calculations are being performed using non-local density functionals (NLDF) which are considered to be more accurate than LDF theory especially for the description of molecular structure and energetics.6,7 Despite the large number of experimental20 and theoretical studies39 of formamide, its structure has been controversial. The peptide moiety was assumed from the early work of Pauling and Corey to be planar, and more recently, however, the planarity of the peptide moiety has been questioned.Two early microwave studies of formamide have reached different conclusions12,13 on the planarity of the peptide moiety. From a theoretical point of view, only recently have very high-level first-principle quantum chemical methods, Hartree–Fock,43 nth order Moller–Plesset perturbation,43 configuration interaction, 41 coupled-cluster36 and DFT38–40 been applied to formamide. To date, no systematic study of the geometries, internal rotational barriers, and vibrational frequencies of formamide using different NLDF has been reported in the literature.The DFT-calculated geometries of formamide are generally better than those predicted by HF theory, while those calculated using the adiabatic connection method (ACM)25 in particular are comparable with MP2, with the remaining NLDFs falling inbetween the HF and MP2 methods.Two transition states (Fig. 1) were found at the DFT level for the internal rotation about the peptide bond of formamide. The DFT-calculated rotational barrier heights for the two transition states range from 18 to 20 kcal molµ1, which are within the experimentally observed rotational barrier heights.17 The vibrational frequencies for formamide are significantly in better agreement with experiment than both the HF and MP2 calculated frequencies.Techniques used: Non-local density functional theory References: 61 Table 1: Comparison of experimental and calculated geometries of formamide Table 2: Calculated geometries for the transition states of formamide Table 3: Comparison of experimental and calculated rotational barriers for formamide Tables 4 and 5: Comparison of experimental and calculated vibrational frequency for formamide Table 6: Comparison of calculated vibrational frequencies for the transition states of formamide Received 15th August 1997; Accepted, 29th September 1997 Paper E/7/06017C References cited in this synopsis 6 T.Zeigler, Chem. Rev., 1991, 91, 651. 7 J. W. Andzelm and E. Eimmer, J. Chem. Phys., 1992, 96, 1280. 10 N. L. Allinger, R. S. Grev, B. F. Yates and H. F. Schaeffer III, J. Am. Chem. Soc., 1990, 112, 114. 11 J. Bojarath, D. H. Kitson, G. Fitzgerald, J. W. Andzelm, J. Kraut and A. T. Hagler, Proteins, 1991, 9, 217. 12 C. C. Costain and J. M.Dowling, J. Chem. Phys., 1953, 32, 158. 13 R. J. Kurland and E. B. Wilson, J. Chem. Phys., 1957, 27, 585. 17 T. Drakenberg and S. Forsen, J. Phys. Chem., 1970, 74, 1. 20 C. L. Brummel, M. Shen, K. B. Hevelt and L. A. Philips, J. Opt. Soc. Am., 1994, B11, 176 and references cited therein. 36 N. Burton, S. S.-L. Chiu, M. M. Davidson, D. V. S. Green, I. H. Hillier, J. J. W. McDouall and M. A. Vincent, J. Chem. Soc., Faraday Trans. 2, 1993, 89, 2631. 38 F. Sim, A. St-Amant, I. Papai and D. H. Salahub, J. Am. Chem. Soc., 1992, 114, 4391. 39 D. A. Dixon and N. Matsuzawa, J. Phys. Chem., 1994, 98, 3967 and references cited therein. 40 J. Florian and N. Matsuzawa, J. Phys. Chem., 1994, 98, 3681. 41 X. C. Wang, J. Nichols, M. Feyereisen, M. Gutowski, J. Boatz, A. D. J. Haymet and J. Simons, J. Phys. Chem., 1991, 95, 10 419. 43 K. B. Wiberg and C. M. Breneman, J. Am. Chem. Soc., 1992, 114, 831. 52 A. D. Becke, J. Chem. Phys., 1993, 98, 5648. *To receive any correspondence (at address in Mexico). Fig. 1 Schematic representations of the two transition states found in this study (TS1 and TS2)

ISSN:0308-2342    

DOI:10.1039/a706017c

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

O O R OH R O R 1 R = Cl 2 R = Br 3 R = Me 16 R = OMe 4 R = Cl 5 R = Br 6 R = Me 7 R = Cl 8 R = Br 9 R = Me HO Me HB Me HA Me Me OH R HO Ph Ph O R 10 R = Cl 12 R = Br 13 R = Me HB HA HO R Ph O R 11 R = Cl 14 R = Br 15 R = Me 17 R = OMe HB Ph Ph Ph O Ph Ph HA 123 16 + O R 23 R = Cl 24 R = Br 25 R = Me H1 H3 H2 O R H4 Me Me Me Me O R 26 R = Me 27 R = OMe O Me Me Me Me H4 H5 H1 H2 H3 R 10 15 8 3 78 2 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 2–3 J. Chem. Research (M), 1998, 0101–0114 Preparation of Some 6-Substituted 2,2-Dimethyl- and 2,2- and 2,4-Diphenyl-naphtho[1,2-b]pyrans W.David Cotterill, Muhammad Iqbal and Robert Livingstone* Department of Chemical and Biological Sciences, The University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK 6-Chloro-, 6-bromo-, and 6-methyl-2,2-dimethyl-, and -2,2- and -2,4-diphenyl-naptho[1,2-b]pyrans are prepared from the appropriate 4-substituted 2H-naphtho[1,2-b]pyran-2-ones and either methylmagnesium iodide or phenylmagnesium bromide; some related compounds and derivatives are also prepared and dimerisation of cylized products from the methylmagnesium iodide reactions affords dimers including a relative of isolapachenole through addition reactions of the intermediate carbonium ion.Decomposition of the respective Grignard complex obtained from 6-chloro-, 6-bromo- and 6-methyl-2H-naphtho[1,2- b]pyran-2-ones (1, 2 and 3) and methylmagnesium iodide with an aqueous solution of ammonium chloride afforded the corresponding 3-(4-chloro-, 4-bromo- and 4-methyl- 1-hydroxynaphthalen-2-yl)-1,1-dimethylprop-2-en-1-ols (4, 5 and 6), all of which decomposed on standing. The structure of the diols 4, 5 and 6 was supported by 1H NMR spectral data. The diols 4, 5 and 6 were dehydrated and cyclized in boiling acetic acid to furnish the 6-chloro- and 6-bromo- 2,2-dimethyl-2H-naphtho[1,2-b]pyrans (7 and 8) and the 2,2,6-trimethyl-2H-naphtho[1,2-b]pyran (9), respectively.Treatment of 6-chloro-2H-naphtho[1,2-b]pyran-2-one (1) with phenylmagnesium bromide, followed by decomposition of the Grignard complex with aqueous ammonium chloride solution, yielded a gum, which on boiling in acetic acid furnished 6-chloro-2,2-diphenyl-2H-naphtho[1,2-b]pyran (10) and 6-chloro-2,3-diphenyl-4H-naphtho[1,2-b]pyran (11). Compounds 10 and 11 were thus formed via the initial 1,2- and 1,4-addition of the Grignard reagent to the 6-chloronaphthopyran- 2-one (1). Similarly 6-bromo- and 6-methyl- 2H-naphtho[1,2-b]pyran-2-ones (2 and 3) afforded the respective 6-substituted 2,2-diphenyl-2H-naphtho[1,2-b]pyrans (12 and 13) and the 2,4-diphenyl-4H-naphtho[1,2-b]pyrans (14 and 15).Decomposition of the Grignard complex from 6-methoxy-2H-naphtho[1,2-b]pyran-2-one (16) gave a dark red gum, which on boiling in acetic acid afforded a small yield of 6-methoxy-2,4-diphenyl-4H-naphtho[1,2-b]pyran (17). The structures of the above compounds were supported by 1H NMR spectral data.Treatment of 6-chloro- and 6-bromo-2,2-dimethyl-2Hnaphtho[ 1,2-b]pyrans (7 and 8) in acetic acid with a few drops of sulfuric acid gave, after 2 days standing, the dimers 6 - c h l o r o / b r o m o - 3 , 4 - d i h y d r o - 2 , 2 - d i m e t h y l - 4 - ( 6 - c h l o r o / b r o m o - 2 , 2 - d i m e t h y l - 2 H- n a p h t h o [ 1 , 2 - b] p y r a n - 3 - y l ) - 2 H - naphtho[1,2-b]pyrans (23 and 24), respectively. The same treatment of 2,2,6-trimethyl-2H-naphtho[1,2-b]pyran (9) furnished a mixture (ca. 1:1) of two dimers, separated by fractional crystallization. They were identified as 3,4-dihydro- 2 , 2 , 6 - t r i m e t h y l - 4 - ( 2 , 2 , 6 - t r i m e t h y l - 2 H- n a p h t h o [ 1 , 2 - b] p y r a n - 3-yl)-2H-naphtho[1,2-b]pyran (25) and 6,6a,6b,7,8,14bh e x a h y d r o - 6 , 6 , 8 , 8 , 1 4 , 1 6 - h e x a m e t h y l d i b e n z o [ h, h p] c y c l o - penta[1,2-c:5,4,3-dpep]bis[1]benzopyran (26).The structure of dimer 26 was verified by comparing its 1H NMR spectrum and mass spectrum with those of isolapachenole (27),1 the dimer of 6-methoxy-2,2-dimethyl-2H-naphtho[1,2-b]pyran (lapachenole). The mechanism for the formation of dimers 23, 24 and 25 is probably similar to that for the dimerization of 3,3,10-trimethyl- 3H-naphtho[2,1-b]pyran.2 It is, therefore, proposed *To receive any correspondence.O R 7 R = Cl 8 R = Br 9 R = Me Me Me O R Me Me + 28 O R Me Me O R Me Me H + 29 23 24 25 H+ –H+ AcO R 21 R = Cl 22 R = Br OH Me Me OO Me O Me Me HB HA OH OH Me HB HA 18 19 20 J.CHEM. RESEARCH (S), 1998 3 that the olefinic bond of the pyran ring of a molecule of the naphthopyran is protonated to give carbonium ion 28, which reacts with another molecule of the naphthopyran to afford carbonium ion 29. This then loses a proton to form the respective dimers 23, 24 and 25. The dimerization of lapachenole (6-methoxy-2,2-dimethyl- 2H-naphtho[1,2-b]pyran) under acidic conditions affords only isolapachenole (27) (85%),3 due to the activating effect of the methoxy group at the 6-position of the monomer.With the weaker activating methyl group at the 6-position, dimer 26 (49%), similar in structure to isolapachenole, and dimer 25 (35%) are formed. However, with the deactivating halogeno group at the 6-position in compounds 7 and 8 only the respective dimer 23 (79%) or 24 (69%) is formed. Treatment of the diols 4 and 5 in pyridine with acetic anhydride resulted in the acetylation of the more nucleophilic phenolic OH to give the monoacetates, 3-(1-acetoxy- 4-chloro/bromo-2-naphthyl)-1,1-dimethylprop-2-en-1-ol (21 and 22, respectively).To complete the series of dimethylnaphthopyrans, 2,2-dimethyl-2H-naphtho[2,3-b]pyran (20) was prepared. Decomposition of the Grignard complex from 2Hnaphtho[ 2,3-b]pyran-2-one (18) and methylmagnesium iodide with aqueous ammonium chloride solution yielded 3-(3-hydroxy-2-naphthyl)-1,1-dimethylprop-2-en-1-ol (19), which on boiling with acetic acid gave 2,2-dimethyl-2Hnaphtho[ 2,3-b]pyran (20). Techniques used: IR and 1H NMR, MS References: 15 Figures: 2 Tables 1–4: 1H NMR data Received, 16th June 1997; Accepted, 17th September 1997 Paper E/7/04178K References cited in this synopsis 1 W. D. Cotterill, R. Livingstone, K. D. Bartle and D. W. Jones, Tetrahedron, 1968, 24, 1981. 2 W. D. Cotterill, S. A. Fairbank, R. Livingstone and R. Peace, J. Chem. Res., 1994, (S) 254; (M) 1489. 3 R. Livingstone and M. C. Whiting, J. Chem. Soc., 1955, 3631.

ISSN:0308-2342    

DOI:10.1039/a704178k

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

H2N 1 R3 R4 R2 R1 R5 + N R4 R3 R2 R1 H 1 2 3 4 5 7 8 9 10 11 12 5a-e: i 5f-h: ii 5a–h 2a–h N R3 R2 R1 H 1 2 3 4 5 7 6 9 10 11 3a–e O 8 N R3 R2 R1 H 1 2 3 4 5 7 6 9 10 11 4a,b,e O 8 + 2a–e iii N S R3 R2 R1 H 1 2 3 4 5 7 6 9 10 11 3f,g 8 N S R3 R2 R1 H 1 2 3 4 5 7 6 9 10 11 4f–h 8 + 2f–h iv 4 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 4–5 J. Chem. Research (M), 1998, 0115–0125 Synthesis of New Cyclopenta-acridinone and -phenothiazine Derivatives Sandrine Morel, Florence Chatel, G�erard Boyer* and Jean-Pierre Galy ESA 6009, Univ. d’Aix-Marseille III, case 552, Avenue Escadrille Normandie-Neimen, 13397 Marseille Cedex 20, France The synthesis of new cyclopenta-acridinones and -phenothiazines by cyclization of N-aryl indanes under acidic conditions or via Bernthsen thionation is reported.Acridines and phenothiazines are well known therapeutic agents1 and some significant derivatives have been prepared with a supplementary heterocyclic fourth ring.3,5,6 We are interested in the preparation of a new class of tetracycles bearing a cyclopentane ring fused to an acridine or phenothiazine moiety.The indane 1 was used as starting material and we prepared both cyclopenta-acridinones and cyclopenta-phenothiazines according to the synthetic pathway shown in Scheme 1. The substitution patterns of the derivatives are given in Tables 1–3. The aminoindane 1 was first arylated with the benzoic acids 5a–e in order to obtain the corresponding N-substituted anthranilic acids 2a–e in 33–66% yields.The next step involved cyclization of these acids by either PPA or sulfuric acid. Depending on the regioselectivity of the cyclization position (5 or 7, Scheme 1), either one or two isomers could be obtained: the angular [a]-fused tetracycle (type 3) and/or its homologue, the linear [b] isomer (type 4). In the case of 2a, 2b and 2e, a mixture of both isomers was obtained, purification and separation of which led to the corresponding 1,2,3,6- tetrahydrocyclopenta[a]acridin-11-ones 3a, 3b and 3e and to Scheme 1 Reagents and conditions: i, Cu, K2CO3, pentan-1-ol, 110 °C, 4–12 h; ii, CH2Cl2, Cu(OAc)2, room temp., 4 h; iii, PPA or H2SO4, 90 °C, 2 h; iv, S8, I2, o-C6H4Cl2, reflux, 6 h Table 1 Synthesis of N-arylamines derivatives 2a–h Starting material Compound no.R1 R2 R3 R4 R5 Product 5a 5b 5c 5d 5e 5f 5g 5h HHHH NO2 HHH HHH NO2 HHHH H OMe NO2 HHH OMe Me CO2H CO2H CO2H CO2H CO2H HHH Cl Br Cl Cl Br Bi(OAc)2 Pb(OAc)3 Pb(OAc)3 2a 2b 2c 2d 2e 2f 2g 2h Table 2 Synthesis of acridinones derivatives 3a–e, 4a, b and e Starting material Compound no.R1 R2 R3 R4 Products 2a 2b 2c 2d 2e HHHH NO2 HHH NO2 H H OMe NO2 HH CO2H CO2H CO2H CO2H CO2H 3a/4a 3b/4b 3c 3d 3e/4e Table 3 Synthesis of phenothiazines derivatives 3f, g and 4f–h Starting material Compound no. R1 R2 R3 R4 Products 2f 2g 2h HHH HHH H OMe Me HHH 3f/4f 3g/4g 4h *To receive any correspondence (e-mail: gerard.boyer@mvcf.u-3mrs.fr).J.CHEM. RESEARCH (S), 1998 5 the linear 1,2,3,5-tetrahydrocyclopenta[b]acridin-10-ones 4a, 4b and 4e. In other cases only the angular acridinones were recovered. Cyclopenta-phenothiazines were also prepared from commercial 1 but using a copper-catalysed arylation with organometallic reagents such as 5f–h. Under mild conditions, the diarylamines 2f–h were synthesized in good yields (64–85%) and subsequently cyclized by Bernthsen thionation in o-dichlorobenzene.Work-up of mixtures gave also the corresponding angular or linear cyclopenta[b] or -[c]-phenothiazines 3f,g and 4f–h. Moreover, difficulties associated with the method of purification and rapid oxidation of the final products could explain the absence of [c]-fused 3h. All the compounds prepared were characterized unambiguously by 1H and 13C NMR spectroscopy. In particular, the multiplet pattern of the C-ring protons of the final products was especially checked: 4-H and 5-H would resonate as two doublets in the case of [a] or [c] fusion, but as two singlets in the case of [b] fusion (4-H and 11-H).We found, for example, two doublets at d 7.55 and 7.31 which correspond to ‘bent’ 1,2,3,6-tetrahydrocyclopenta[a]acridin-11-one 3a and two singlets at 7.46 and 8.02 ppm respectively for linear 1,2,3,5-tetrahydrocyclopenta[b]acridin-1-one 4a (4-H and 11-H). All the 13C NMR chemical shifts are given in the Experimental section of the full paper.Techniques used: 1H and 13C NMR Referneces: 13 Scheme:1 Received, 28th July 1997; Accepted, 16th September 1997 Paper E/7/05425D References cited in this synopsis 1 Phenothiazines and 1,4-Benzothiazines. Chemical and Biomedical Aspects (Bioactive Molecules, Vol. 4), ed. R. R. Gupta, Elsevier, Amsterdam, 1988; R. M. Acheson, Acridines, Wiley, New York, 1973. 3 J. P. Galy, S. Morel, G. Boyer and J. Elguero, J. Heterocycl. Chem., 1996, 33, 1551. 5 G. Boyer, J. P. Galy, R.Faure, J. Elguero and J. Barbe, J. Chem. Res., 1990, (S) 350; (M) 2601; M. Boyer, J. P. Galy, R. Faure, J. Elguero and J. Barbe, Magn. Reson. Chem., 1991, 6, 638. 6 G. Boyewr, J. P. Galy and J. Barbe, Heterocycles, 1995, 41, 487; G. Boyer, J. P. Galy, R. Faure and J. Barbe, Magn. Reson. Chem., 1994, 32, 537. Table 4 1H NMR chemical shifts of N-aryl amines 2a–h (d values, [2H6]DMSO) Amine Proton 2a 2b 2c 2d 2e 2f 2g 2h 1-H 2-H 3-H 4-H 5-H 7-H 8-H 9-H 10-H 11-H 12-H OCH3 CH3 2.83 2.00 2.83 7.17 6.95 7.08 9.59 7.10 7.32 6.69 7.87 —— 2.79 1.99 2.79 7.15 6.91 7.04 9.11 7.16 7.06 — 7.37 3.70 — 2.84 2.02 2.84 7.26 7.04 7.14 10.29 6.99 8.09 — 8.66 —— 2.85 2.07 2.85 7.26 7.06 7.14 9.80 7.70 — 7.43 8.07 —— 2.76 1.97 2.76 7.06 6.66 6.78 9.90 — 8.17 7.02 8.03 —— 2.80 1.99 2.77 7.08 6.88 7.00 7.97 7.04 7.19 6.76 ——— 2.84 2.06 2.84 7.08 6.73 6.84 5.40 7.03 6.85 —— 3.79 — 2.77 1.97 2.75 7.04 6.91 7.81 6.93 7.00 ——— 2.20 Table 5 1H NMR chemical shifts of acridinones 3a–e, 4a,b and e (d values, [2H6]DMSO) Acridinone Proton 3a 4a 3b 4b 3c 3d 3ea 4ea 1-H 2-H 3-H 4-H 5-H 6-H 7-H 8-H 9-H 10-H 11-H OCH3 3.53 2.07 2.87 7.55 7.31 11.51 7.45 7.65 7.17 8.14 —— 2.95 2.05 2.95 7.46 12.13 7.58 7.66 7.18 8.18 — 8.02 — 3.55 2.07 2.86 7.52 7.29 11.50 7.45 7.34 — 7.58 — 3.83 2.96 2.05 2.96 7.33 11.56 7.48 7.34 — 7.60 — 8.03 3.83 3.48 2.08 2.88 7.60 7.32 12.09 7.54 8.35 — 8.85 —— 3.50 2.08 2.86 7.61 7.31 11.95 8.29 — 7.85 8.32 —— 3.62 2.18 2.96 7.56 7.21 11.16 — 8.65 7.25 8.77 —— 2.99 2.12 2.99 7.30 11.20 — 8.68 7.29 8.86 — 8.24 — aCDCl3 as solvent.Table 6 1H NMR chemical shifts of phenothiazines 3f, g and 4f–h (d values, [2H6]DMSO) Phenothiazine Proton 3f 4f 3g 4g 4h 1-H 2-H 3-H 4-H 5-H 6-H 7-H 8-H 9-H 10-H 11-H OCH3 CH3 2.62 1.96 2.69 6.79 6.45 8.37 6.63 6.96 6.68 6.87 ——— 2.70 1.93 2.68 6.74 — 6.89 6.72 6.94 6.69 8.42 6.59 –— 2.63 1.97 2.72 6.79 6.42 8.14 6.63 6.59 — 6.56 — 3.64 — 2.70 1.93 2.68 6.77 — 6.56 — 6.58 6.58 8.19 6.58 3.65 — 2.70 1.93 2.70 6.75 — 6.72 — 6.76 6.57 8.30 6.56 — 2.

ISSN:0308-2342    

DOI:10.1039/a705425d

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

HO OTs H 9 8 vi O H 11 vii HO OH H 10 5 iv v 3 R1 = NH2; R2 = CO2H 4 R1 = OH; R2 = CO2H 5 R1 = OH; R2 = CO2Me 6 R1 = OTHP; R2 = CO2Me 7 R1 = OTHP; R2 = CH2OH 8 R1 = OTHP; R2 = CH2OTs i ii iii iv v R1 R2 H O O O O OH HO 12 D-Mannitol O O CHO 13 i O O CH OR CH3 14 R = H 15 R = OTs O O H 16 15 iv 10 v ii iii N MeO OMe OMe 17 N MeO OMe OMe 18 OH H i,ii + C5H11 OH H 26 + NH MeO OMe O 27 18 NH MeO OMe O 19 OH H iii iv 1 v,vi 2 6 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 6–7 J.Chem. Research (M), 1998, 0126–0142 Enantioselective Synthesis and Absolute Configuration of (R)-(+)-Lunacridine and (S)-(+)-Lunacrine Ramesh C. Anand* and N. Selvapalam Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India (R)-(+)-Lunacridine 1 has been synthesised in 97.3% e.e. using a chiron approach through L-valine and D-mannitol as the starting compounds in order to corroborate its absolute configuration. The prenylated quinolinone alkaloids lunacridine and lunacrine have been isolated from Lunasia sp.1 of different sources in optically active form and given structures 1 and 2 respectively on the basis of degradative studies, spectroscopic data2 and a synthesis of the racemates (in extremely poor yield.3 An attempt was also made by Grundon and coworkers4 to assign absolute configurations to the title compounds through asymmetric synthesis in less than 1% e.e.The configurational assignments to compounds 1 and 2 were based on the assumption that (S)-peroxycamphoric acid on reaction with an olefin yields an (S)-epoxide and by comparison of the direction of specific rotation of their compound 1 with that reported for the natural product.In view of very low optical induction and magnitude of the specific rotation, [a]D 25=µ0.19 for 1, any assignment of absolute configuration to 1 and 2 needs further support to be unequivocal. Recently Barr et al.5 have used a cumbersome resolution procedure to prepare the title compounds in poor overall yield.Therefore, the present studies were planned in order to accomplish an unambiguous and highly enantioselective synthesis of 1 and 2 so as to assign absolute configurations to these compounds on firm grounds. The strategy used for the present asymmetric synthesis is based on a chiron approach wherein optically pure (S)-(+)-valine and (D)-(+)-mannitol were used as the starting compounds. The synthetic investigations carried out are delineated below.Synthesis of (S)-Epoxide 11.—(i)(S)-Valine as starting compound (Scheme 1). (ii) D-Mannitol as starting compound (Scheme 2). Transformation of 11 into Compounds 1 and 2.·First approach (Scheme 3). *To receive any correspondence. Scheme 1 Reagents and conditions: i, HNO2, 0 °C; ii, Amberlyst-15–MeOH; iii, DHP-H+; iv, LiAlH4; v, TosCl-py; vi, MeOH–H+; vii, NaOMe Scheme 2 Reagents and conditions: i, NaIO4–aq. MeCN; ii, MeMgI; iii, TosCl–py; iv, LiCuMe2; v, MeOH–H+ Scheme 3 Reagents and conditions: i, BuLi at µ78 °C; ii, 11; iii, anhyd.HCl–OEt2; iv, CH2N2; v, TosCl–py; vi, aq. NaOHO MeO2C O H 11 i O O H ii HO H MeO2C 21 20 THPO H MeO2C 22 THPO H HO2C 23 iv v iii CO2Me NH O MeO H OTHP 24 NH O MeO H OTHP 25 vi HO vii N O MeO H OTHP 26 MeO viii Me N O MeO H OH 1 MeO Me ix N O MeO 2 O Me x,xi H J. CHEM. RESEARCH (S), 1998 7 Second approach (Scheme 4). The synthetic material had [a]D 30=+28.47° (c, 1.5 in EtOH).Its mp and IR, UV and 1H NMR data were identical with those reported for the natural product. Optical purity was also checked by derivatization of 1 with Mosher’s reagent followed by 1H NMR analysis of the resulting compounds. The transformation 1h2 has already been reported.1 Financial assistance from CSIR, New Delhi, through the project 1(1343)/95-EMR-II is gratefully acknowledged. Techniques used: IR, 1H NMR, UV spectroscopy, polarimetry References: 9 Schemes: 4 Received, 7th April 1997; Accepted, 16th September 1997 Paper E/7/02352I References cited in this synopsis 1 J.R. Price, Aust. J. Chem., 1959, 12, 458; S. Goodwin and E. C. Horning, J. Am. Chem. Soc., 1959, 81, 1908; H. C. Beyerman and R. W. Rooda, Proc. K. Ned. Akad. Wet., Ser. B, 1959, 62, 187; S. Goodwin, A. F. Smith, A. A. Velasquez and E. C. Horning, J. Am. Chem. Soc., 1959, 81, 6209. 2 S. Goodwin, J. N. Shoolery and L. F. Johnson, J. Am. Chem. Soc., 1959, 81, 3065. 3 E. A. Clarke and M. F. Grundon, J. Chem. Soc., 1964, 438; R. Oels, R. Storrer and D. W. Young, J. Chem. Soc., Perkin Trans. 1, 1977, 2546. 4 R. M. Bowman, G. A. Gray and M. F. Grundon, J. Chem. Soc., Perkin Trans. 1, 1973, 1051. 5 S. A. Barr, D. R. Boyd, N. D. Sharma, T. A. Evans, J. F. Malone and V. D. Mehta, Tetrahedron, 1994, 50, 11219. 6 R. C. Anand and N. Selvapalam, Synth. Commun., 1994, 24, 1994. 7 A. Chattopadhyay and V. R. Mamdapur, J. Org. Chem., 1995, 60, 585. Scheme 4 Reagents and conditions: i, CH2(CO2Me)2; ii, NaCl– DMSO; iii, Amberlyst-15–MeOH; iv, DHP–H+; v, aq. NaOH–H+; vi, DCC followed by methyl 2-amino-3-methoxybenzoate; vii, 2 equiv. NaH–PhMe; viii, KOH–DMF–Me2SO4; ix, MeOH–H+; x, TosCl–py; xi, aq. NaOH

ISSN:0308-2342    

DOI:10.1039/a702352i

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

O 1 O Cl Cl 9 O 2 O Cl Cl 10 O AcO 3 Cl AcO 11 Cl O 4 O Cl Cl 12 5 Cl Cl 13 6 Cl Cl 14 7 Cl Cl 15 O O 8 8 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 8–9 J. Chem. Research (M), 1998, 0143–0150 Manganese-mediated Stereoselective and Chemoselective trans-Dichlorination of Alkenes with Tetradecyltrimethylammonium Permanganate– Trimethylchlorosilane Braja G. Hazra,* Mahendra D. Chordia, Sourav Basu, Bharat B. Bahule, Vandana S. Pore and Dinabandhu Naskar Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411 008, India An excellent reagent for the chemo- and stereo-selective trans-dichlorination of alkenes in high yield has been formulated by mixing tetradecyltrimethylammonium permanganate, a relatively stable crystalline solid, with trimethylchlorosilane in methylene dichloride.Although not widely recognised, it is well established1 that the formation of vic-dichlorides from addition of molecular chlorine to olefins has limited synthetic utility owing to the occurrence of side reactions.Moreover, reaction of gaseous chlorine with alkenes presents a potential environmental hazard and quantitative utilization of chlorine in this reaction is often hard to work out. Several other reagents add chlorine to double bonds. Sulfuryl chloride2 reacts readily with most ethylenic compounds to yield saturated dichloro derivatives with evolution of sulfur dioxide. Reaction of trichloroamine3 with olefins provides a simple means for the preparation of vic-dichlorides.Phosphorus pentachloride,4 antimony pentachloride, 5 iodobenzene dichloride,6 tetrabutylammonium iodotetrachloride7 and copper(II) chloride8 have been examined as chlorinating agents with good results in certain cases. cis-Vicinal dichlorinations of olefins by molybdenum( VI)–acetyl chloride9 and manganese(III) acetate–calcium chloride10 have been reported. trans-Vicinal dichlorinations of olefins with manganese dioxide–trimethylchlosilane11 and MnO2–MnCl2–acetyl chloride12 and acetal chlorination with MnO2–trimethylchlorosilane13 have been more recently documented.However non-homogeneity of these inorganic based reagents in commonly used organic solvents limits their wider synthetic applications. In order to overcome this difficulty Marko and Richardson have used14,15 benzyltriethylammonium permanganate and oxalyl chloride in methylene dichloride, a widely used organic solvent for the trans-dichlorination of alkenes.This reagent system is unstable above µ35 °C. Moreover, use of benzyltriethylammonium permanganate has severe drawbacks in terms of safety due to its decomposition16–18 with explosive violence above 80–90 °C. This instability arises because the easily formed benzyl radical initiates a chain reaction, during drying or when the reagent is handled neat. In view of these factors it was expected that replacement of the aromatic functionality of the quaternary ammonium salt by a long-chain hydrocarbon moiety, e.g. tetradecyl, would give rise to a much safer quaternary permanganate salt of increased stability.We have recently prepared tetradecyltrimethylammonium permanganate (TDTAP) and demonstrated19a its use as an excellent new reagent for the chemo- and stereo-selective trans-dibromination of alkenes. Differential thermal analysis of TDTAP has shown its decomposition to be a stepwise exothermic process which starts at 102.3 °C, with the thermogram reaching a maximum at 119.5 °C.This clearly indicates that TDTAP decomposes passively at a relatively higher temperature compared with earlier reported20 quaternary permanganate salts. In fact, violet crystals of TDTAP are stable at room temperature for a few days and can be stored in a brown bottle at 0 °C for months which permits its ready access whenever required. In continuation of our earlier work towards exploring the use of TDTAP as a reagent for important synthetic transformations,19 we report herein a highly stereoand chemo-selective trans-dichlorination of alkenes with tetradecyltrimethylammonium permanganate (TDTAP) and trimethylchlorosilane (TMCS).Use of the non-hazardous *To receive any correspondence (e-mail: hazra@ems.ncl.res.in). Table 1 trans-Dichlorination of alkenes with TDTAP–TMCS Starting compound Product Yield (%) No reaction 96 88 87 62 84 92 90 —J. CHEM. RESEARCH (S), 1998 9 and relatively stable TDTAP in combination with TMCS for trans-dichlorination of alkenes has not been reported earlier in the literature.A violet-coloured solution of TDTAP in methylene dichloride at 0–3 °C changed immediately to brown on treatment with TMCS. A solution of the olefin in methylene dichloride was added to this mixture which was then stirred at 0–3 °C for 1.5 h. During this period the reaction mixture turned green. Along with the trans-dichlorinated products, we isolated hexamethyldisiloxane (Me3Si–O–SiMe3) as one of the end products in this reaction.The results are summarized in Table 1. Our TDTAP–TMCS reagent displays high chemoselectivity as evidenced by a lack of reaction of the a,b-unsaturated double bond at C-16 of pregnenolone acetate 3, the electrondeficient double bond of carvone 4 or with the benzylic as well as the electron-deficient double bond of coumarin 8. In the stigmasterole derivative 2 the (22E)-double bond is sterically crowded by the (24S)-ethyl group and D-ring of the steroid, thus hindering the approach of the chlorinating species.The only product isolated in this case is the 2,3-diaxial dichloride 10 (88%). The reaction of 16-dehydropregnenolone acetate 3 and carvone 4 in methylene dichloride with excess of chlorine gas at 0 to 3 °C for 1.5 h furnished a complex mixture of polychlorinated products. Allylic chlorination and chlorination a to the ketone along with addition of chlorine to the double bond took place in both cases.Column chromatographic purification of the polychlorinated products on silica gel using ethyl acetate–hexane (2:98) as an eluent afforded 3b - a c e t o x y - 5 , 6 , 1 6 , 1 7 - t e t r a c h l o r o - 5 a- p r e g n a n - 2 0 - o n e (0.127 g) and 3b-acetoxy-5,6,16,17,21-pentachloro-5a-pregnan- 20-one (0.202 g) from 0.712 g of compound 3. Both these compounds were obtained as foamy masses, which could not be crystallised. The structures of these two products were assigned from 1H and 13C NMR and from elemental analysis.Further elution with the same solvent system furnished two more compounds (0.066 g and 0.096 g) which were not characterised. We failed to isolate any 5,6-dichlorinated product 11 from this reaction. In the case of carvone 4, a mixture of polychlorinated compounds of identical polarity (41%) was isolated. IR, 1H NMR and mass spectroscopic data suggested to be a mixture of 2,3,4,4,6,8,8,9,10-nonachloro- and 2,3,4,6,8,9,10-heptachloro-carvone. No trace of the 9,10-dichlorocarvone 12 was found in this chlorination reaction.Treatment of compounds 3 and 4 with excess of TDTAP–TMCS in methylene dichloride under identical conditions afforded the dichlorides 11 and 12, respectively, as the only products in yields (78 and 53%) comparable with those obtained when a single equivalent of TDTAP had been employed. This excellent chemoselectivity, even with an excess of the reagent, clearly ruled out the possibility that molecular chlorine is generated in the reaction mixture and strongly suggests21 the formation of an oxochloro manganese intermediate as a chlorinating species in this trans-dichlorination reaction.trans-Dichlorination of Alkenes: a Typical Procedure.—To a magnetically stirred violet solution of TDTAP (376 mg, 1 mmol) in methylene dichloride (10 cm3) was added trimethylchlorosilane (458 mg, 4.2 mmol) in methylene dichloride (2 cm3) at 0 °C.A brown solution resulted immediately. To this cholest-2-en-6-one22 1 (384 mg, 1 mmol) in methylene dichloride (5 cm3) was added dropwise over 5 min and the reaction mixture was stirred at 0–3 °C for 1.5 h. During this period the brown colour of the reaction mixture changed to dark green. The mixture was then stirred with a 10% solution of sodium bisulfite (10 cm3) and was brought to room temp. and changed to colourless. From this mixture methylene dichloride was removed under reduced pressure and the mixture was extracted with ethyl acetate (3Å50 cm3).The ethyl acetate extracts were combined and washed with water (2Å30 cm3), saturated brine (2Å30 cm3) and dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure to afford a solid product (2S,3S)-2,3-dichlorocholestan- 6-one 9 (437 mg, 96%); mp 134 °C (hexane– diethyl ether) (lit.,23 131 °C); [a]D 28=+34.9 (c 1.7, CHCl3); vmax (nujol)/cmµ1 1712 (C�O), 650; dH (200 MHz; CDCl3) 0.75 (s, 3 H, 18-H3), 0.94 (d, 6 H, J 7.0 Hz, 26-H3, 27 H3), 1.0 (d, 3 H, J=7 Hz, 21-H3), 1.12 (s, 3 H, 19-H3), 2.9 (dd, 1 H, J 2.0, 12 Hz, 5-H), 4.43–4.65 (m, 2 H, 2,3-H); m/z 454 and 456 (M+), 439, 418, 403, 384, 367, 341, 247, 191, 107, 93 (100%).Compounds 10–15 were prepared using this general procedure. We thank Dr Debabrata Chatterjee, CSMCRI, Bhavnagar, and Dr Basudeb Achari, IICB, Calcutta, for helpful discussions. Two of the authors (S. B. and D.B. N.) thank CSIR, New Delhi, for Senior and Junior Research Fellowships respectively. Techniques used: IR, 1H NMR, MS, polarimetry, DTA References: 27 Received 31st January 1997; Accepted, 16th September 1997 Paper E/7/00726D References cited in this synopsis 1 P. B. D. De La Mare and R. Bolton, Electrophilic Addition to Unsaturated Systems, Elsevier, New York, 1966, p. 105; M. L. Poutsma, J. Am. Chem. Soc., 1965, 87, 2161. 2 M. S. Kharash and H. C. Brown, J. Am. Chem. Soc., 1939, 61, 3432. 3 K. W. Fried and P. Kovacic, Synthesis, 1969, 135. 4 L. Spiegler and J. M. Tinker, J. Am. Chem. Soc., 1939, 61, 940; D. P. Wyman, J. Y. C. Wang and W. R. Freeman, J. Org. Chem., 1963, 28, 3173. 5 L. Uemeura, A. Onoe and M. Okano, Bull. Chem. Soc. Jpn., 1974, 47, 692; V. L. Heasley, K. D. Rold, D. R. Titterington, C. T. Leach, B. T. Gipe and D. B. McKee, J. Org. Chem., 1976, 41, 3997; S. Uemura, O. Sasaki and M. Okano, J. Chem. Soc., Chem. Commun., 1971, 1064. 6 D. D.Tanner and G. C. Gidley, J. Org. Chem., 1968, 33, 38; M. C. Lasne and A. Thuillier, Bull. Soc. Chim. Fr., 1974, 249. 7 R. E. Buckles and D. F. Knaack, J. Org. Chem., 1960, 25, 20. 8 W. C. Baird, J. H. Surridge and M. Buza, J. Org. Chem., 1971, 36, 3324. 9 W. A. Nungent, Tetrahedron Lett., 1978, 3427. 10 K. D. Donnelly, W. E. Fristad, B. J. Gellerman, J. R. Peterson and B. J. Selle, Tetrahedron Lett., 1984, 25, 607. 11 F. Bellesia, F. Ghelfi, U. M. Pagnoni and A. Pinetti, J. Chem. Res. (S), 1989, 108. 12 F. Bellesia, F. Ghelfi, U. M. Pagnoni and A. Pinetti, Synth. Commun., 1991, 21, 489. 13 F. Bellesia, M. Boni, F. Ghelfi, R. Grandi, U. M. Pagnoni and A. Pinetti, Tetrahedron, 1992, 48, 4579. 14 I. E. Marko and P. F. Richardson, Tetrahedron Lett., 1991, 32, 1831. 15 P. F. Richardson and I. E. Marko, Synlett, 1991, 733. 16 J. A. Morris and D. C. Mills, Chem., Ind. (London), 1978, 446. 17 H. Jager, J. Lutlof and M. W. Meyer, Angew. Chem., Int. Ed. Engl., 1979, 18, 786. 18 H. J. Schmidt and H. J. Schafer, Angew. Chem., Int. Ed. Engl., 1979, 18, 787. 19 (a) B. G. Hazra, M. D. Chordia, B. B. Bahule, V. S. Pore and S. Basu, J. Chem. Soc., Perkin Trans. 1, 1994, 1667; (b) B. G. Hazra, T. Pavan Kumar and P. L. Joshi, Liebigs Ann., 1997, 1029. 20 H. Karaman, R. J. Barton, B. E. Robertson and D. G. Lee, J. Org. Chem., 1984, 49, 4509. 21 A manuscript consisting of EPR, UV–visible and other spectroscopic evidence for the reactants, chlorinating species and the end product is currently under preparatio

ISSN:0308-2342    

DOI:10.1039/a700726d

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

NOH C R1 R2 + TBSCl DMF, imidazole 64–88% N C R1 R2 OTBS (1) X R N OTBS 1 i, BH3–THF ii, HCl iii, NaOH X R NH2 2 N X H 3 R + 10 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 10–11 J. Chem. Research (M), 1998, 0151–0168 The Reduction of O-(tert-Butyldimethylsilyl) Aldoximes and Ketoximes and Electronic Effect Studies on the Novel Rearrangement that occurs with a Borane–Tetrahydrofuran Complex Margarita Ortiz-Marciales,* Elmer Cruz, Ileana Alverio, Dyliana Figueroa, Jos�e F.Cordero, Jos�e Morales, Jos�e A. Soto, Hiresh Dashmana and Carlos Burgos Department of Chemistry, University of Puerto Rico, Humacao University College, CUH Station, Hunacao, Puerto Rico 00791 The reduction of aromatic and cyclic O-(tert-butyldimethylsilyl) oximes with various reducing reagents, such as NaBH4, LiAlH4, 9-BBN, Li(Me3Si)2NBH3 and BH3–THF, was investigated. Since the fundamental work of Feuer and Vincent,1 it has been well established that borane and boron hydrides reduce oximes, oxime ethers and acyl oximes affording N-monosubstituted hydroxylamines or primary amines, depending on the structure and reaction conditions.In 1985, Itsuno et al.16 first enantioselectively reduced O-trimethylsilylacetophenone oxime with borane complexed to 1,3,2-oxazaborolidine formed in situ by the reaction of the chiral amino alcohol, (S)-(µ)-2-amino-3-methyl-1,1-diphenylbutan-1-ol and borane. Although the O-(trimethylsilyl)oximes are readily prepared, 19 they are very susceptible to hydrolysis.20 We developed a new and convenient method for the large scale synthesis of O-(tert-butyldimethylsilyl) oximes,21 that were also envisioned as novel intermedites for the synthesis of chiral primary amines,22 and other organic compounds.23,24 Tillyer et al.27 reported the enantioselective reduction of keto O-TBS oxime ethers by Corey’s reagent,28 for the synthesis of cyclic amino alcohols.However, they observed a lower yield for the 6-methoxy-substituted aromatic ring.Similarly, Liu and co-workers29 found recently only 5% of hydroxylamine along with an unidentified compound, when 6-benzyloxy- 2,3-dihydrobenzofuran 3-O-trimethylsilyloxime was reduced with borane and norephedrine. For the O-TBS analogue, it was reported that no reaction took place. In this paper, we describe our studies on the reduction of O-(tert-butyldimethylsilyl) oximes with various reducing reagents and the role that electronic effects play on the reaction pathways.Representative aromatic and aliphatic O-TBS oximes were prepared in excellent yield by the reaction of the corresponding oxime with tert-butyldimethylchlorosilane, DMF and imidazole, [eqn. (1)], using a modification of our previously reported method.21 Initially, we found that the O-TBS moiety hinders the aromatic oximes from reduction with NaBH4, LiAlH4, 9-BBN, Li(Me3Si)2NBH3 nd BH3–THF at room temperature.24 Afterwards, we investigated the reduction of O-TBS oximes with BH3–THF under more vigorous reaction conditions. The results of the reductions of the corresponding silylated aryl oximes are summarized in Table 1.Benzylamine (2a) was obtained in excellent yield from the reduction of the O-TBS benzaldoxime (1a) with BH3–THF complex after 3 h under reflux conditions. Borane reduction of the acetophenone O-TBS oxime at reflux temperature for 4 h afforded 21% of the expected a-methylbenzylamine (2b), 49% yield of N-ethylaniline (3b) and a minor amount of N-monosubstituted *To receive any correspondence (e-mail: M_Ortiz@cuhad.upr.clu.edu). Table 1 Reduction of aryl O-TBS ketoximes with borane Starting material Yield 1 X R Reaction conditions (%)a 2:3b aaa bbbccc def HHHHHH Me Me Me MeO NO2 Cl HHH Me Me Me Me Me Me Me Me Me 2BH3–THF, heat, 5 h 2BH3–THF, 1 MgBr2–Et2O, 5 h 3BH3–THF, 1.5 MgBr2–Et2O, 5 h 1BH3–THF, heat, 6 h 2BH3–THF, heat, 4 h 2BH3–THF, heat, 4 h, MgBr2–Et2O 2BH3–THF, 25 °C, 9 days 2BH3–THF, heat, 4 h 3BH3–THF, heat, 4 h 2BH3–THF, heat, 8 h 2BH3–THF, heat, 8 h 2BH3–THF, heat, 8 h 83c 80 88 65 86 88 24(12)e 80 70 75 74 55 a99:1 97:3 90:10 45:55d 31:69 43:57 21:79 36:64d 30:70 25:75 a99:1 63:36 aIsolated overall yields.Product purity determination by GC–MS and by 300 MHz 1H and 13C NMR. bDetermined by capillary GC. cComparison with authentic samples. dRatio of isolated products by column chromatography. eIsolated hydroxylamine.N OTBS [ ] n n = 1,2 NH2 [ ] n i, BH3–THF, heat ii, HCl iii, NaOH (2) J.CHEM. RESEARCH (S), 1998 11 hydroxylamine. Reduction with 3 mol. equiv. of or a longer reaction time gave no hydroxylamine. Only the isomeric amines 2b and 3b were isolated and characterized by their spectroscopic data. As illustrated in entries 2, 3 and 6, the addition of magnesium bromide–diethyl ether promotes the rearrangement of the silylated benzaldoxime and acetophenone oxime, probably owing to the coordination of magnesium to the oxygen, making the silyloxy moiety a better leaving group.Moreover, entries 8 and 10 clearly show that the yield of the reductive rearranged product increases with an increase in the electron- releasing ability of the para-substituent, while a strong electron-withdrawing group such as NO2 (entry 11) favours formation of the primary amine. Although the formation of secondary anilines from the borane reduction of aromatic oximes and oxime ethers is unprecedented in the literature, borane can act as a Lewis acid promoting a reductive type of rearrangement for O-TBS oximes.In the case of aliphatic cyclic O-TBS oximes, [eqn. (2)], we observed that O-TBS cyclopentanone and cyclohexanone oximes, when treated with BH3–THF under reflux, generated only cyclopentyl- and cyclohexyl-amine in a 70 and 68% yield, respectively. Techniques used: IR, 1H NMR, 13C NMR, GC–MS References: 49 Received, 4th August 1997; Accepted, 17th September 1997 Paper E/7/05622B References cited in this synopsis 1 H.Feuer and B. F. Vincent, J. Am. Chem. Soc., 1962, 84, 3771. 16 S. Itsuno, M. Nakano, K. Miyazaki, H. Masuda and K. Ito, J. Chem. Soc., Perkin Trans. 1, 1985, 2039. 17 Y. Sakito, Y. Yoneyoshi and G. Suzukamo, Tetrahedron Lett., 1988, 29, 233. 19 A. Singh, V. D. Gupta, G. Srivastova and R. C. Mehrota, J. Organomet. Chem., 1974, 64, 145. 20 E. W. Colvin, Silicon in Organic Synthesis, Butterworths, London, 1981. 21 M. Ortiz-Marciales, J. F. Cordero, S. Pinto and I. Alverio, Synth. Commun., 1994, 24, 409. 22 C. Burgos, J. Sato, M. DeJesus and M. Ortiz-Marciales, 211th ACS National Meeting, New Orleans, 1966. 23 M. Ufret, E. Cruz and M. Ortiz-Marciales, 203th ACS National Meeting, San Francisco, 1992. 24 M. Ortiz-Marciales, E. Cruz, I. Alverio, H. Dhasmana and D. Velazquez, 206th ACS National Meeting, Chicago, 1993. 27 R. D. Tillyer, C. Boudreau, D. Tschaen, U. H. Dolling and P. J. Reider, Tetrahedron Lett., 1995, 36, 4337. 28 E. J. Corey and R. K. Bakshi, J. Am. Chem. Soc., 1987, 109, 5551. 29 J. T. Dougherty, J. R. Flisak, J. Hayes, I. Lantos, L. Liu and L. Tucker, Tetrahedron: Asymmetry, 1997, 8

ISSN:0308-2342    

DOI:10.1039/a705622b

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

NNHPh Ph Cl N NH NNH2 S Ph SMe Ph + H2NNHC(S)SMe –HCl 1 2 N N S Ph NNH2 Ph N N S Ph NNO Ph 3 4 N N S Ph NN Ph 5 PhCHO Zn–AcOH H2NNHC(S)NH2 CHPh + MeSH O Me Cl NNHPh O Me S NNHPh SMe H2NN 6c 7 + 2 N S N SMe Me NNHPh 8 –H2O NNHPh Ph Cl 1 NNHC(S)SR2 R1 Me + N N N Ph NHC(S)SR2 Me R1 Ph N N S Ph SR2 Ph NHN C(R1)Me N N S Ph Ph NN C(R1)Me 12 –R2SH 11 13a R1 = 2-C4H3S b R1 = 2-C4H3O c R1 = 2-C5H4N d R1 = 3-C5H4N a R1 = 2-C4H3S, R2 = Me b R1 = 2-C4H3O, R2 = Me c R1 = 2-C5H4N, R2 = Me d R1 = 3-C5H4N, R2 = Me 9 a R1 = 2-C4H3S, R2 = Et b R1 = 2-C4H3O, R2 = Et 10 12 J.CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 12–13 J. Chem. Research (M), 1998, 0169–0179 Reactions with Hydrazonoyl Halides. Part 15.1 A Synthetic Approach to 2,3-Dihydrothiadiazoles Hussein A. Emam,a Hussein F. Zohdib and Adbou O. Abdelhamid*b aDepartment of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt bDepartment of Chemistry, Faculty of Science, Cairo University, Giza, Egypt Hydrazonoyl halides 1 and 6a–f reacted with methyl hydrazinecarbodithioate (2) and methyl 3-[1-(aryl)alkylmethylidene] hydrazinecarbodithioates (9a–d or 10a,b), in ethanolic triethylamine solution, to afford the corresponding 2-hydrazono- 3,5-diphenyl-2,3-dihydro-1,3,4-thiadiazoles (3), 5-methyl-2-methylsulfanyl-6-phenylhydrazono-1,3,4-thiadiazine (8) and 2,3-dihydro-1,3,4-thiadiazoles 17–20a–f, respectively.It has been reported that dithiocarbazoic acid reacts with haloacetophenones2 and a-halo compounds3 to give 1,3,4-thiadiazines and 2-halomethyl-1,3,4-thiadiazoles, which have been reported to exhibit antiprotozoal,4 antiviral,5 bactericidal6 and fungicidal7 properties.However, the reaction of hydrazonoyl halides with dithiocarbazoate has not yet been reported.8 In this paper, we report a study of this reaction. Treatment of N-phenylbenzohydrazonoyl chloride (1) with methyl hydrazinecarbodithioate (2) in ethanolic triethylamine afforded a product which gave analytical and spectral data in accord with its formulation as 2-hydrazono-3,5-diphenyl- 2,3-dihydro-1,3,4-thiadiazole (3).Compound 3 was authentically obtained by other routes: (a) via reaction9 of 1 with thiosemicarbazide; (b) by reduction of 2-nitrosoimino- 3,5-diphenyl-2,3-dihydro-1,3,4-thiadiazole10 (4). Also, 3 reacted with benzaldehyde to give the corresponding hydrazone 5 (see Scheme 1). In contrast to the above results, 1-chloro-2-phenylhydrazonopropan-2-one (6c) reacted with 2 to give a product formulated as 5-methyl-2-methylsulfanyl- 6-phenylhydrazono-1,3,4-thiadiazine (8) according to elemental analysis and spectral data (see Scheme 2).Treatment of N-phenylbenzohydrazonoyl chloride (1) with methyl 3-[1-(2-thienyl)ethylidene]hydrazinecarbodithioate (9a) in ethanolic triethylamine at room temperature gave the 2,3-dihydro-1,3,4-thiadiazole 13a (see Scheme 3). In contrast, treatment of 1 with ethyl 3-[1-(2-thienyl)ethylidene]hydrazinecarbodithiote 10a), at room temperature, produced the same product (13a).These results indicate the following facts: (a) structure 12 is not the final product; (b) 13a is formed via loss of methane-(or ethane-)thiol; (c) structure 11 is ruled out (see Scheme 3). Similarly, compounds 9b–d reacted with 1 to give 2,3-dihydro-1,3,4-thiadiazole derivatives 13b–d, respectively. The products 13a–d are assumed to be formed via elimination of alkanethiol from the corresponding cycloadduct 12, resulting from 1,3-dipolar cycloaddition of nitrile imide to the C�S of the methyl or ethyl dithiocarbazoate [similar to the reaction of hydrazonoyl halides with substituted thiourea9] (see Scheme 4).The formation of 13a–d can also be explained by the reaction of a dithiocarbazoate of general formula 9 (or 10) with the hydrazonoyl chloride 1, in the presence of a base such as triethylamine or potassium hydroxide. The corresponding 2,3-dihydro-1,3,4-thiadiazole can be easily obtained through the nucleophilic attack of the thiolate group followed by ring closure and methane-(or ethane-)thiol elimination.The elimination of the thiole moiety was confirmed by isolation of the same product (13a) when using 10a and 1, respectively. All attempts to isolate the hydrazone 14 were *To receive any correspondence. Scheme 1 Scheme 2 Scheme 3N N N S Ph SR2 N R1 Me Ph H 14 12 S N N Ph N H N Me R1 Ph SR2 Me(R1)C NNHC(S)R2 9(10) PhC NNPh 9(10) + – 1 + Et3N N N S Ph Ph N N C(R1)Me 13 –R2SH 1 base N N S Ph NNH2 Ph S Me O + S Me NNHCSNH2 13a 1 + 3 15 16 (1) R3CO Cl(Br) NNHPh N N S R3CO Ph NN C(R1)Me 17–20a–f + 9a–d(10a,b) 17 R1 = 2-C4H3S 18 R1 = 2-C4H3O 19 R1 = 2-C5H4N 20 R1 = 3-C5H4N a R3 = EtO b R3 = PhNH c R3 = Me d R3 = Ph e R3 = 2-C4H3O f R3 = 2-C4H3S 6,17–20 6a–f J.CHEM. RESEARCH (S), 1998 13 unsuccessful. Unequivocal support for structure 13 was provided by the preparation of 13a via two routes.The first involves the reaction of 5-hydrazino-2,4-diphenyl-1,3,4-thiadiazole 3 with 2-acetylthiophene (15), in propan-2-ol, the second by the reaction of N-phenylbenzohydrazonoyl chloride (1) with 1-[1-(2-thienyl)ethylidene]thiosemicarbazide (16), in boiling ethanol. All the products were identical with 13a [see eqn. (1)]. In order to study the effect of a carbonyl group on the reactivity of the hydrazonoyl halides, the reaction of a-oxohydrazonoyl halides 6a–f with 9a–d, in ethanolic triethylamine at room temperature, was investigated and found to give the corresponding 2,3-thiadiazoles 17–20a–f.The structures of the products were confirmed by their spectra and alternative synthesis. Thus, the reaction of 10a,b with 6a,b in ethanol containing equimolar amounts of triethylamine gave products identical with 17a,b and 18a,b respectively (see Scheme 5). Techniques used: 1H NMR, IR, mass spectrometry Tables: 2 References: 23 Received, 16th July 1997; Accepted, 19th September 1997 Paper E/7/05088G References cited in this synopsis 1 Part 14: H.F. Zohdi, H. A. Emam and A. O. Abdelhamid, Phosphorus, Sulfur, Silicon Relat. Elem., in press. 2 I. Ya. Postovskii, A. D. Sinegibskaya, A. P. Novilova and L. P. Sidorova, Tezisy Dokl. Nauchn. Sess. Khim. Tekhnol. Org. Soedin. Sery Sernistykh Neftei, 14th, ed. I. G. Bakhtalze, 1975 (pub. 1976), pp. 207–208 (Chem. Abstr., 1978, 88, 190771q). 3 W. Thiel, H. Viola and R. Mayer, Ger. (East) Pat., DD 211,450 (Cl. C07D285/12), 1984 (Chem. Abstr., 1985, 102, 9565d). 4 S. K. Mallick, A. R. Martin and R. G. Lingard, J. Med. Chem., 1971, 14, 528. 5 A. Andolsek, B. Stanovnik, M. Tisler and P. Schauer, J. Med. Chem., 1971, 3. 6 P. N. Dahl, T. E. Achary and A. Nayak, Indian J. Chem., 1975, 3. 7 S. R. Smith, J. Indian Chem. Soc., 1975, 52, 734. 8 A. S. Shawali, Chem. Rev., 1993, 93, 2731. 9 P. Wolkoff, S. T. Nemeth and M. S. Gibson, Can. J. Chem, 1975, 53, 3211. 10 A. S. Shawali and H. M. Hassaneen, Indian J. Chem., 1976, 14B, 425. Scheme 4 Scheme

ISSN:0308-2342    

DOI:10.1039/a705088g

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

O2N X 1a,b,f,g PhS NC ButOK–DMF 0 °C VNS O2N X N C 2a,b,f,g O2N X H2N O2N X HN OHC 3b 4a,b,f,g H3O+ r.t. H3O+ heat X H2N X HN 6a–g 5a,b,f,g H2, 10% Pd–C, 40 lbf in–2 R H2N EtOH H2, 10% Pd–C, 40 lbf in–2 EtOH PATHWAY A (R = H) PATHWAY B X N 7a–f N R air Cl X = (a); N N CH3 (b,c,d,e); (f); N (g); R = H (a,b,f,g); Me (c); Bun (d); Ph (e) RC(OR¢)3 reflux NH2 NH CHO 8 N N 9 R1, R2 = Me 10 R1, R2 = Ph R1 R2 O 14 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 14–15 J. Chem. Research (M), 1998, 0180–0187 New Synthesis of Fused Pyrimidine Derivatives via ortho-(Isocyanomethyl)nitroaromatic Compounds Stanis ý law Ostrowski* Institute of Organic Chemistry, Polish Academy of Sciences, ul.Kasprzaka 44/52, PL 01-224 Warszawa, Poland An efficient synthesis of functionalized fused pyrimidine derivatives from the respective ortho-(isocyanomethyl)nitroarenes is described: hydrolysis of the isocyano group in the title isocyanides followed by catalytic reduction of the nitro group and subsequent cyclocondensation of the diamine formed with orthoesters leads to the final products.Since the early years of this century several studies on the synthesis and structure–activity relationships of pyrimidine derivatives have been reported.1,2 A pyrimidine nucleus is embedded in a large number of alkaloids, drugs, antibiotics, agrochemicals and antimicrobial agents.1 In addition, many simple fused pyrimidines (purines, pteridines) are biologically active by themselves2b,c or are essential components of very important naturally occurring substances.The availability of starting materials has been a limiting factor for the preparation of fused pyrimidine derivatives8,9 such as quinazolines and various tricyclic heteroaromatic compounds. Many of these products can be easily synthesized from the corresponding ortho-aminobenzylamines or their fused heteroanalogues.10 However, the rather difficult access to these key intermediates11a,b or to their precursors11c is a serious limitation for this synthesis.We have described lately12 a general method for the synthesis of ortho-isocyanomethyl nitro-aromatic/heteroaromatic compounds of type 2 (Scheme), based on the Vicarious Nucleophilic Substitution (VNS) of hydrogen. In this work a practical application of the above method for the synthesis of fused pyrimidines is described. One can expect that the wide spectrum of nitroarenes available as starting materials will broaden considerably the frontiers of this synthesis.The desired ortho-(N-formylaminomethyl)nitroaromatic compounds of type 3 or diamino intermediates 5 were effi- ciently obtained from the above isocyanides 2. Hydrolysis of these isocyanides under mild conditions (MeOH–H2O, catalytic amount of HCl, room temperature, 10 h) gave formamides such as 3b. Subsequent reduction of the nitro group (10% Pd–C, 40 lbf inµ2, EtOH, 4 h) followed by cyclisation was expected to afford a pyrimidine derivative of type 6 (Pathway A).Instead, this model compound 2-(N-formylaminomethyl)- 1-nitronaphthalene (3b), while hydrogenated under these conditions, gave small amounts of the desired product 6b (s10%) and N-(1-aminonaphthalen-2-ylmethyl)- formamide (8) in ca. 40% yield which cyclized efficiently to 6b only at 200 °C (EtOH, sealed tube, 10 h). Moderate amounts of the diamino derivative 5b were also found. The collected dihydro compound 6b underwent a spontaneous oxidation to 7b in ca. 45% yield (calculated on the starting isocyanide 2b). Additionally, the transformation of 5b into 6b in the reaction with triethyl orthoformate, then oxidation to 7b, raised the overall yield to 53%. The above approach, due to the number of various operations it required, had no practical value from an experimental point of view and was not therefore applied to the synthesis of other derivatives. The alternative pathway B was more efficient.For example, the exhaustive hydrolysis of 2b to 4b (concentrated HCl, MeOH–H2O, reflux, 1 h) and subsequent hydrogenation (10% Pd–C, EtOH, 40 lbf inµ2, 4 h) afforded diamine 5b, which was converted by treatment with triethyl orthoformate into the fused pyrimidine 7b in 58% overall yield. The last step · an aromatization of the dihydro derivative (6) · occurred spontaneously. In addition to its simplicity, the method B allowed functionalization at C-2 by using diverse orthoesters (see compounds 7c–e). All the synthesized products are listed in Table 1.In some cases, owing to condensation of the diamines (5) with two molecules of the orthoester, small quantities of the corresponding N-acetyl- or N-benzoyl-dihydropyrimidine derivatives (9 or 10) were formed as by-products. To avoid this side-process, the condensation with the orthoester was carried out in boiling ethanol (procedure C). Lower temperatures and dilution of the reaction mixture improved selectivity. The condensation was stopped at the stage of the dihydro compounds (6), giving also considerably higher yields.This procedure was demonstrated for the preparation of 6e (84%) and 6g (61%). The product 6e when left at room temperature quickly started to undergo spontaneous aromatization to 7e. *E-mail: Stan@ichf.edu.pl SchemeN N Cl 7a N N 7b N N 7c Me N N 7d N N 7e Ph N NH 6e Ph [ox.] 7f N N N N Me 6g N NH N J. CHEM. RESEARCH (S), 1998 15 Compound 7f exemplifies the application of the above methodology to the synthesis of purines using imidazole derivatives.Approaches to purines from imidazoles are not exhaustively described in the literature.16 Currently we are in the midst of exploring this new type of synthetic possibility with the use of methods from our laboratory17 and the complete results will be published soon.18 This work was supported by the State Committee for Scientific Research, Grant 2 P303 087 07. Techniques used: 1H NMR, MS, TLC References: 18 Tables: 1 Schemes and Figures: 4 Received, 6th May 1997; Accepted, 25th June 1997 Paper E/7/03092D References cited in this synopsis 1 D.J. Brown, in The Chemistry of Heterocyclic Compounds, The Pyrimidines, ed. E. C. Taylor, Wiley, New York, 1994. 2 (a) W. L. F. Armarego, in The Chemistry of Heterocyclic Compounds, Fused Pyrimidines, Part I: Quinazolines, ed. D. J. Brown, Interscience, New York, 1967; (b) J. H. Lister, ibid., Part II: Purines, ed.D. J. Brown, Wiley–Interscience, New York, 1971; (c) D. J. Brown, ibid., Part III: Pteridines, ed. E. C. Taylor, Wiley, New York, 1988; (d) T. J. Delia, ibid., Part IV: Miscellaneous Fused Pyrimidines, ed. E. C. Taylor, Wiley, New York, 1992. 8 Bischler’s synthesis: A. Bischler, Ber. Dtsch. Chem. Ges., 1891, 24, 506; W. L. F. Armarego and J. I. Smith, J. Chem. Soc. C, 1966, 234; Riedel’s synthesis: A. Riedel, Ger. Pat. 174941, 1905; M. T. Bogert and E. M. McColm, J.Am. Chem. Soc., 1927, 49, 2650; W. L. F. Armarego, J. Chem. Soc., 1962, 561; Niementowski’s synthesis: S. Niementowski, J. Prakt. Chem., 1895, 51(2), 564; ref. 2(a), pp. 74–78. 9 (a) D. Chakravarti, R. N. Chakravarti, L. A. Cohen, B. Dasgupta, S. Datta and H. K. Miller, Tetrahedron, 1961, 16, 224; (b) S. C. Pakrashi, J. Bhattacharyya, L. F. Johnson and H. Budzikiewicz, Tetrahedron, 1963, 19, 1011; (c) G. C. Mu�noz and R. Madro�nero, Chem. Ber., 1962, 95, 2182. 10 (a) B. R. Baker, R.E. Schaub, J. P. Joseph, F. J. McEvoy and J. H. Williams, J. Org. Chem., 1952, 17, 164; (b) N. J. Leonard and M. J. Martell Jr., Tetrahedron Lett., 1960, 25, 44; (c) S. C. Bell and S. J. Childress, J. Org. Chem., 1962, 27, 1691; (d) T. Goto, Y. Kishi, S. Takahashi and Y. Hirata, Tetrahedron, 1965, 21, 2059. 11 (a) H. E. Zaugg and W. B. Martin, Org. React., 1965, 14, 52; (b) S. Kano, Y. Tanaka, S. Sugino and S. Hibino, Synthesis, 1980, 695; (c) Y. Tomioka, K. Ohkubo and M.Yamazaki, Chem. Pharm. Bull., 1985, 33, 1360. 12 M. Maikosza, A. J. Kinowski and S. Ostrowski, Synthesis, 1993, 1215. 13 K. Schofield and T. Swain, J. Chem. Soc., 1949, 1367. 14 T. Koyama, T. Hirota, F. Yagi, S. Ohmori and M. Yamata, Chem. Pharm. Bull., 1975, 23, 3151. 15 A. Bendich, P. J. Russell Jr. and J. J. Fox, J. Am. Chem. Soc., , 76, 6073. 16 (a) J. Sarasin and E. Wegmann, Helv. Chim. Acta, 1924, 7, 713; (b) A. H. Cook and E. Smith, J. Chem. Soc., 1949, 2329, 3001; (c) G. Shaw and D. N. Butler, J. Chem. Soc., 1959, 4040; (d) R. N. Naylor, G. Shaw, D. V. Wilson and D. N. Butler, J. Chem. Soc., 1961, 4845; (e) K. Kadir, G. Shaw and D. Wright, J. Chem. Soc., Perkin Trans. 1, 1980, 2728; (f) K. E. Andersen and E. B. Pedersen, Liebigs Ann. Chem., 1985, 921; (g) P. R. Birkett, H. King, Ch. B. Chapleo, D. F. Ewing and D. Mackenzie, Tetrahedron, 1993, 49, 11029. 17 (a) S. Ostrowski, Synlett, 1995, 253; (b) S Ostrowski, Heterocycles, 1996, 43, 389. 18 S. Ostrowski, in preparation. Table 1 Fused pyrimidine derivatives Mp (T/°C)b Product Procedure Yield (%)a (solvent) B A B B B B C B C 52 53 58 44e 60 21f 84g 21 61 135–137 (CHCl3)c 95–98 (CHCl3–MeOH)d 82 (subl.) oil 149–151 (CHCl3) semi-crystalline 171–173 (CHCl3)h semi-crystalline aTotal yields based on the isocyanide (2). bUncorrected. cLit. mp 143 °C.13 dLit. mp 102–103 °C.14 eTraces of 9 were found. fSmall amount of 10 was isolated (s5% yield). gSmall amount of 7e was formed (6%), also product 6e decomposed slowly to yield 7e. hLit., mp 183–184 °C.15

ISSN:0308-2342    

DOI:10.1039/a703092d

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

O M N O N OEt EtO O O M X (H2O) n O (H2O) n Mn, Cu, Zn, Cd, Hg Co Ni 133 Cl Cl OH M n X 16 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 16–17 J. Chem. Research (M), 1998, 0201–0213 Dinuclear Complexes of Diethyl 2-(2-Carboxyphenylhydrazono)-3-oxopentanedioate with some Transition Metal Ions Yousry M. Issa,* Nour T. Abdel-Ghani and Maha F. Abo El-Ghar Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt Manganese(II), cobalt(II), copper(II), zinc(II), cadmium(II) and mercury(II) complexes of diethyl 2-(2-carboxyphenylhydrazono)- 3-oxopentanedioate have been prepared and characterized by IR, 1H NMR and UV spectroscopy, magnetic moment measurements and thermogravimetric analysis.Coordination compounds with several dinucleating ligands have been studied as models for naturally occurring systems1 and in the domain of metallo-enzymes and homogeneous catalysis. The synthesis of dinuclear complexes involves choice of a suitable ligand which can coordinate through more than one chelation centre.5 Diethyl 3-oxopentanedioate can be regarded as a precursor for 2-arylhydrazone derivatives having two separate centres of chelation. This article deals with the synthesis and structural characterization of diethyl 2-(2-carboxyphenylhydrazono)-3-oxopentanedioate (H3L) complexes with some divalent metal ions, MnII, CoII, NiII, CuII, ZnII, CdII and HgII.The ligand acts as a b-oxo ester and an a-oxo 2-carboxyphenylhydrazone: it may chelate to two metal ions via the enolic OH and CO (unconjugated ester) on one side, and the NH, CO (conjugated ester) and OH (carboxylic) on the other side.Diethyl 2-(2-carboxyphenylhydrazono)-3-oxopentanedioate was prepared according to the method described in the literature.14 The complexes were prepared by mixing 1 mol equiv. of the ligand with 2 mol equiv. of the metal chloride in ethanol and boiling for 10 min. NaOH (3 mol equiv.) was then added gradually with continuous stirring while boiling.The mixture was diluted with distilled water and the product was collected by filtration and washed several times with ethanol till the filtrate was colourless. The complexes, M2LCl.nH2O [M=MnII, CoII, CuII, ZnII, CdII, HgII; n=2–6] and Ni2L.OH.6H2O, were isolated in 60–65% yield. The structure of the dinuclear complexes may be proposed as: The IR spectra of the MII–H3L complexes showed masking of the vNH of the hydrazo group and vOH of the carboxylic group attached to the aromatic moiety by a very broad band centred at ca. 3400 cmµ1 which can be assigned to vOH of the water molecules coordinated to the metal ion. New bands at 1275–1264 cmµ1 corresponding to a dOH(H2O) deformation and at 690 cmµ1 assigned to a H2O rocking vibration17 were observed. vC——O appeared as a medium-intensity band at 1732–1676 cmµ1 which could be taken as evidence for the participation of C�O groups in chelation. The CH bending vibration band of the ·CH2·CO· moiety at 1420 cmµ1 disappeared on chelation, indicating its involvement in the coordination through the enolic form of the ligand.The appearance of a new band at 1610, 1611 and 1613 cmµ1 for the CoII, ZnII and CdII complexes, respectively, emphasized the presence of C�C as a result of enolization. New bands observed at 468–428 and 406–416 cmµ1 were assigned to vM·N 19 and vM·O 20 respectively. The 1H NMR spectrum of the ligand showed two adjacent triplets at d 1.20 and 1.30, and two quartets at d 4.10 and 4.35 corresponding to the six protons (two CH3) and four protons (two CH2) of the two ethyl groups, respectively.A singlet was observed at d 3.95 corresponding to the active methylene group.21 The aromatic protons were shown as multiplet signals at d 7.25, 7.75, 7.90 and 8.05. The NH and CO2H protons showed signals at d 13.89 and d 3.40, respectively, which disappeared on deuteration. [Cd2LCl.2H2O] and [Hg2LCl.2H2O] showed disappearance of the NH proton, indicating the involvement of the NH in chelation.Disappearance of the active methylene protons as well as the appearance of a new singlet at d 7.0 corresponding to the methine proton (�CH) indicated enolization of the oxo group as a result of chelation. The participation of the CO2H proton in chelation cannot be accounted for from the 1H NMR spectra because of the water peak that appeared as a strong sharp singlet at the same position (d 3.5).Thermogravimetric analysis curves showed no mass loss below 150 °C, indicating absence of water of hydration in the complexes. Removal of coordinated water molecules started at about 200 °C. This was supported by the appearance of an endothermic peak in the DTA curves over the same temperature range. The decomposition of the MnII, CoII, CuII and ZnII complexes proceeded as a one-step combustion, associated by an exothermic peak in the DTA curve, at 330–490 °C, leading to a final product as MnO2, Co2O3, CuO or ZnO associated with their corresponding metal chlorides. The final residue of the NiII complex amounted to 28%, indicating the formation of NiO.The data were in conformity with the metal content obtained from EDTA titration. The electronic absorption band of [Mn2LCl.2H2O] at 27 144 cmµ1 suggested a tetrahedral structure and the value of the magnetic moment meff (5.21 mB per metal ion) was as expected for a high-spin 3d5 system.22 Bands at 17 500 and 26 247 cmµ1 for [Co2LCl.6H2O] and [Ni2L.OH.6H2O] assigned to 4T1g(F)h4T1g(P) and 3A2g(F)h3T1g(P) transitions, respectively, reflected the octahedral geometry around the CoII and NiII metal ions, while the values of meff (3.97 mB and 3.00 mB per metal ion, respectively) were typical of those reported for high-spin CoII ions23 and were in the same range as reported for octahedral geometry around NiII ions.24 The magnetic moment of [Cu2LCl.2H2O] was 1.64 mB per metal ion, a lower value than that normally reported for an unpaired electron in the CuII metal ion and which may be attributed to a spin-exchange interaction between the two CuII ions.25 The electronic spectrum showed a band at 24 746 *To receive any correspondence.J.CHEM. RESEARCH (S), 1998 17 cmµ1 assigned to a ligand–metal charge transfer, probably a p–p* transition.26 ZnII, CdII and HgII ions were diamagnetic in their complexes. Techniques used: IR, 1H NMR, UV, magnetic moment measurements, TG References: 26 Tables: 4 (formula, elemental analyses, magnetic moment, UV, IR, 1H-NMR and TG) Received, 27th May 1997; Accepted, 19th September 1997 Paper E/7/03623J References cited in this synopsis 1 K.Takahashi, Y. Nishida, Y. Maeda and S. Kida, J. Chem. Soc., Dalton Trans., 1985, 2375. 5 M. Tanaka, M. Kitaoka, H. Okawa and S. Kida, Bull. Chem. Soc. Jpn., 1976, 49, 2469. 14 (a) C. B�ulow and W. Hopfner, Ber. Dtsch. Chem. Ges., 1901, 34, 71; (b) C. B�ulow and H. Goller, Ber. Dtsch. Chem. Ges., 1911, 44, 2835. 17 R. C. Mishra, B. K. Mahapatra and D. Panda, J. Indian Chem. Soc., 1983, 58, 80. 19 E. P. Powell and N. Sheppard, Spectrochim Acta, 1961, 17, 68. 20 C. Djordjevic, Spectrochim. Acta, 1961, 17, 448. 21 B. P. Dailey and J. W. Shoolery, J. Am. Chem. Soc., 1955, 77, 3977. 22 D. H. L. Goodgame and F. A. Cotton, J. Chem. Soc., 1961, 3735. 23 A. T. Casey and S. Mitra, in Theory and Application of Molecular Paramagnetism, ed. E. A. Boudreaux and I. N. Mulay, Wiley, New York, 1976. 24 G. M. Abou El-Reash, Synth. React. Inorg. Met.-Org. Chem., 1993, 23, 825. 25 H. C. Rai and B. N. Sharma, Asian J. Chem., 1995, 7, 775. 26 A. K. Gregson, R. L. Martin and S. Mitra, Proc. R. Soc. London, Ser. A, 1971,

ISSN:0308-2342    

DOI:10.1039/a703623j

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

M N N N N NH2 Cl Cl NH2 Cl 5,10-bis-(2-aminophenyl)-15,20-bis-(2,6-dichlorophenyl)porphyrin ( cis-ab) M N N N N NH2 Cl Cl Cl Cl NH2 5,15-bis-(2-aminophenyl)-10,20-bis-(2,6-dichlorophenyl)porphyrin ( trans-ab) Cl M = H2 M = MnIII 1-MnIII M = FeIII 1-FeIII 1 M = H2 M = MnIII 2-MnIII M = FeIII 2-FeIII 2 M N N N N NH2 Cl Cl Cl 5,15-bis-(2-aminophenyl)-10,20-bis-(2,6-dichlorophenyl)porphyrin ( trans-aa) M N N N N NH2 Cl Cl NH2 Cl 5,10-bis-(2-aminophenyl)-15,20-bis-(2,6-dichlorophenyl)porphyrin ( cis-aa) NH2 M = H2 M = MnIII 3-MnIII M = FeIII 3-FeIII 3 M = H2 M = MnIII 4-MnIII M = FeIII 4-FeIII 4 Cl Cl 18 J.CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 18–19 J. Chem. Research (M), 1998, 0214–0230 New Substituted Tetraphenyl Porphyrins: Synthesis, NMR Characterization and Manganese(III) and Iron(III) Complexes Giovanni Bruno,a Stefania De Luca,a Carla Isernia,b Roberto Fattorusso,b Filomena Rossi,a Carlo Pedonea and Giancarlo Morelli*a aCentro Universitario di Recerca sui Peptidi Bioattivi, and Centro di Studio di Biocristallografia, CNR, Via Mezzocannone 4, I-80134 Napoli, Italy bDipartimento di Scienze Ambientali, Seconda Universit`a di Napoli, Via Arena 22, I-81100 Caserta, Italy Synthetic strategies for new substituted tetraphenylporphyrins and their iron(III) and manganese(III) complexes are reported together with 1H NMR studies on free bases allowing identification of the porphyrin isomers.Metalloporphyrins, especially those of FeIII and MnIII, have been extensively studied, for oxidative catalytic purposes, as models of haem-containing oxygenases1 and peroxidases.2 Owing to the ease of synthesis, the metalloporphyrin catalysts used in biomimetic studies have been of the meso-tetraphenylporphyrin type (TPP).3 Among these, iron(III) tetrakis(ortho- dichlorophenyl)porphyrinate, TDCPPFeCl, has been demonstrated as being a very efficient oxidation catalyst, since both electron deficiency and steric bulk are present in molecules with ortho-chloro groups.Here we report the synthesis of new iron(III) and manganese( III) tetraphenylporphyrins (shown in Fig. 1) carrying both ortho-chloro substituents and reactive NH2 groups on the phenyl rings. The presence of NH2 groups gives the opportunity to insert these molecules in supramolecular structures such as peptides. The strategies for porphyrin synthesis and iron(III) and manganese(III) insertion are reported as well as a first Fmoc–amino acid adduct. 1H NMR studies on the free bases allow the identification of the different porphyrin isomers. We have used the mixed aldehyde condensation method16 by reacting 2,6-dichlorobenzaldehyde (1 mol equiv.), 2-nitrobenzaldehyde (1 mol equiv.) and pyrrole (2 mol equiv.) when a mixture of 5,10-bis-(2,6-dichlorophenyl)-15,20-bis-(2-nitrophenyl) porphyrin and 5,15-bis-(2,6-dichlorophenyl)-10,20- bis-(2-nitrophenyl)porphyrin was obtained in approximately *To receive any correspondence.Fig. 1 Schematic representation of the four isomers of the metal porphyrins under study, with the adopted nomenclature and abbreviation for each isomerJ. CHEM. RESEARCH (S), 1998 19 equimolar amounts. Moreover, by considering the fact that the presence of ortho substituents on the meso-phenyl groups prevents the free rotation of the phenyl groups at room temperature, 18 each compound is a mixture of two atropoisomers, aa or ab, depending on whether the two nitro substituents are present on the same or opposite sides of the porphyrin plane.Subsequent treatment of the porphyrin mixture with tin(II) chloride afforded the corresponding aminophenylporphyrins. Silica gel chromatography of the mixture enabled separation of the four purified porphyrins (1, 2, 3 and 4 in order of increasing polarity), identified by 1H NMR spectroscopy and by considerations of their polarity as the cis-ab isomer (1), the trans-ab isomer (2), the trans-aa isomer (3) and the cis-aa isomer (4).The NMR identification of the different cis–trans isomers was based on the b-pyrrole protons. To distinguish between the aa and ab atropisomers we examined the signals corresponding to protons H3 and H5 of the phenyl rings carrying the chloro substituents. In principle, in the case of the two trans isomers different patterns are exhibited by these protons, depending on the atropisomer. In fact, if both the NH2 groups are on the same side of the porphyrin plane (trans-aa isomer) the two H3 protons that are positioned on the same side as the NH2 groups are magnetically different from the two H5 protons positioned on the opposite side; therefore two resonances are expected.In contrast, in the case of the trans-ab atropisomer the four H3 and H5 protons are all magnetically identical and might resonate as a unique doublet. Metal insertion was easily obtained by reacting the free porphyrin bases with an excess (30–100 fold) of M2+ as the acetate salt, according to the usual procedures for metal insertion into porphyrin rings.21 The reactions were monitored by UV–VIS changes in the Soret and visible regions of the spectrum.None of these new tetraphenylporphyrin metal complexes, or the parent free bases, showed significant atropisomerization at room temperature. Moreover, we also proved the absence of atropisomerization, by TLC analysis, after 3 h of stirring of a solution in DMF at 80 °C.These experimental conditions are suitable for amide bond formation between the NH2 groups of the porphyrin moiety and the carboxylic groups of protected amino acids. Thus we have obtained the adducts [Fmoc-Glu(OBut)]2–(2-Mn) and [Fmoc-Asp(OBut)]2–(2-Mn), in which the Cp carboxylic groups of, respectively, two protected glutamic acid or aspartic acid molecules [Na-(fluoren-9-ylmethyloxycarbonyl)- g-(tert-butoxycarbonyl)-L-glutamic acid or Na-(fluoren-9-ylm e t h y l o x y c a r b o n y l ) - b- ( t e r t - b u t o x y c a r b o n y l ) - L- a s p a r t i c acid] are covalently bonded to the amino groups of the trans- ab isomer of the manganese(III) porphyrinate (2-Mn).Although some covalent peptide–porphyrin compounds have been recently synthesised,11 they contain natural haem or deuterohaem as the porphyrin moiety. [Fmoc-Glu(OBut)] 2-(2-Mn) and [Fmoc-Asp(OBut)]2-(2-Mn) are starting blocks for the preparation of peptide–porphyrin compounds based on synthetic TPP derivatives which could be more suitably used for catalytic purposes.The preparation of the other amino acid–and peptide– metalloporphyrin adducts starting from the metalloporphyrins described here is at present in progress. Techniques used: 1H NMR, UV–VIS References: 23 Scheme: 1 Tables: 2 Fig. 2: 1H NMR spectrum of 1 in CDCl3 at 298 K Fig. 3: Expanded regions of 1H NMR spectra for 1 (cis ab) and 3 (trans aa) showing b-pyrrole proton resonances in CDCl3 at 298 K Fig. 4: Expanded regions of the 1H NMR spectra for compounds 2 (trans ab) and 3 (trans aa) showing H3, H5 and H4 proton resonances in CDCl3 at 298 K Received, 5th June 1997; Accepted, 22nd September 1997 Paper E/7/03930A References cited in this synopsis 1 (a) D. Mansuy, Pure Appl. Chem., 1990, 62, 741; (b) D. Mansuy and P. Battioni, in Metalloporphyrins in Catalytic Oxidations, ed. R. A. Sheldon, Marcel Dekker, New York, 1994. 2 B. Meunier, Chem. Rev., 1992, 92, 1411. 3 (a) I. Tabushi and N. Koga, Tetrahedron Lett., 1979, 20, 3681; (b) E. Guilmet and B. Meunier, Tetrahedron Lett., 1980, 21, 4449. 11 (a) F. Nastri, A. Lombardi, G. Morelli, O. Maglio, G. D’Auria, C. Pedone and V. Pavone, Chem. Eur. J., in press; (b) C. T. Choma, J. D. Lear, M. J. Nelson, P. L. Dutton, D. E. Robertson and W. F. DeGrado, J. Am. Chem. Soc., 1994, 116, 8562; (c) T. Sasaki and E. T. Kaiser, J. Am. Chem. Soc., 1989, 111, 380; (d) L. Casella, M. Gullotti, L. De Gioia, E. Monzani and F. Chillemi, J. Chem. Soc., Dalton Trans., 1991, 2945; (e) D. R. Benson, B. R. Hart, X. Zhu and M. B. Doughty, J. Am. Chem. Soc., 1995, 117, 8502. 16 J. S. Lindsey and R. W. Wagner, J. Org. Chem., 1989, 54, 828. 18 N. Nishino, H. Mihara, H. Kiyota, K. Kobata and T. Fujimoto, J. Chem. Soc., Chem. Commun., 1993, 162. 21 J. W. Buchler, in Porphyrins, ed. D. Dolphin, Academic Press, New York, vol. 3, 1979.

ISSN:0308-2342    

DOI:10.1039/a703930a

出版商:RSC    

年代:1998

数据来源: RSC