摘要:

MeO OH MeO O CO2H I O MeO O 1 2 3 4 O MeO O CH X O MeO CH X OH OCH2CH2A 1 iii ii i vi O MeO CH X 2a bc d X = Cl X = F X = Br X = H a b c d e f g h i j X = Cl, A = NMe2 X = Cl, A = N(CH2CH2)2O X = Cl, A = N(CH2CH2)2CH2 X = Cl, A = N(Et)2 X = Cl, A = N(CH2CH2)2 X = F, A = NMe2 X = F, A = N(CH2CH2)2O X = F, A = N(CH2CH2)2CH2 X = F, A = N(CH2CH2)2 X = F, A = N(Et)2 4 Y OCH2CH2A a b c d e f g h i j k X = Cl, A = NMe2, Y = H X = Cl, A = N(CH2CH2)2O, Y = H X = Cl, A = N(CH2CH2)2CH2, Y = H X = Cl, A = N(CH2CH2)2, Y = H X = Cl, A = N(Et)2, Y = H X = F, A = NMe2, Y = H X = F, A = N(CH2CH2)2O, Y = H X = F, A = N(CH2CH2)2CH2, Y = H X = F, A = N(CH2CH2)2, Y = H X = Cl, A = NMe2, Y = OH X = Cl, A = NMe2, Y = OMe 5 O MeO O CH2 X iv, v vi, vii 3a X = Cl viii, ix viii, x viii, xi O Ar OH CH Ar O Ar O+MgBr Br– CH Ar O CH Ar Ar + Br– O CH Ar O CH Ar O CH Ar Ar + Nu Ar + Br– Nu = H–, MeO– Nu Ar MgBr2•O(Et)2 202 J.CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 202–203 J.Chem. Research (M), 1997, 1412–1422 Synthesis of 3-(p-Halobenzyl)-4-aryl-2H-chromenes as Selective Ligands for Antiestrogen-binding Sites Natarajan Srikanth,a Oi-Lian Kon,b Siu-Choon Nga and Keng-Yeow Sim*a aDepartment of Chemistry, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260 bDepartment of Biochemistry, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260 A series of 3-(p-halobenzyl)-4-aryl-2H-chromenes is prepared in good yields via a two-step sequence from the corresponding 3-benzylidenechromanones (homoisoflavanones).Non-steroidal antiestrogens of triphenylethylene type, principally tamoxifen, have been successfully used in the treatment of hormone-dependent tumours, especially breast cancer.1,2 Antiestrogens bind to two intracellular proteins, viz. the estrogen receptor (ER) and antiestrogen-binding sites (AEBS). Whether AEBS have any role in mediating the nonreceptor- dependent inhibition of cellular proliferation is unresolved.We have previously reported the synthesis and biological studies of a series of basic ethers of 3-(p-halophenyl)- 4-aryl-2H-chromenes3,4 and benzofurans5,6 which bind to AEBS with equivalent or greater affinity than tamoxifen and display no significant interaction with ER. We report herein the synthesis of a series of basic ethers of 3-(p-halobenzyl- 4-aryl-2H-chromenes derived from 3-benzylidenechromanones as a continuation of a project to prepare nonisomerizable antiestrogens for structure–activity studies which could provide an insight into the functional role of antiestrogen-binding sites. The methodology used for the synthesis of the title compounds 5a–i is depicted in Scheme 1.The precursor chromanone 1 was synthesised by treating m-methoxyphenol with 3-bromopropionic acid, followed by cyclisation of acid I using polyphosphoric acid (PPA).7 Base catalysed condensation of the desired aldehydes with the chromanone 1, in the presence of a catalytic amount of sodium hydroxide in refluxing ethanol, afforded the 3-benzylidenechromanones 2a–d in good yields.8 Conjugative reduction of the 3-benzylidenechromanone 2a with sodium borohydride and nickel hexahydrate9 followed by oxidation with pyridinium chlorochromate (PCC)10 afforded 3-benzylchromanone (3a).Reaction of 3a with the arylorganolithium reagent followed by acidcatalysed dehydration of the tertiary alcohol afforded 5a in moderate yield, which might be due to the enolisation of the keto group and subsequent preferential deprotonation of the enol hydroxy moiety.This prompted us to explore an alternative approach of reacting the 3-benzylidenechromanones 2a–d with the arylorganolithium reagents to give good yields of the allylic alcohols 4a–j which were transformed into the target compounds 5a–i by treatment with magnesium bromide etherate followed by lithium aluminium hydride.6 This interesting transformation must involve an allylic rearrangement, presumably via the intermediacy of carbocations, as previously observed for the benzofuran analogues. 6 A possible mechanism for this interesting transformation is illustrated in Scheme 2. Quenching of the highly coloured magnesium complex (intermediate) with water or methanol yielded the *To receive any correspondence. Scheme 1 Reagents and conditions: i, BrCH2CH2COOH, NaHCO3, NaOH, H2O, reflux; ii, PPA, 90 °C, 1 h; iii, p-XC6H4CHO, NaOH, EtOH, r.t.; iv, NiCl2.6H2O, NaBH4, THF, MeOH; v, PCC, CH2Cl2, r.t.; vi, p-BrC6H4OCH2CH2A, BuLi, THF, µ78 °C, aq.NH4Cl; vii, H+, MeOH, reflux; viii, MgBr2.OEt2, Et2O, r.t.; ix, LiAlH4, x, H2O; xi, MeOH Scheme 2 Allylic transformationJ. CHEM. RESEARCH (S), 1997 203 rearranged allylic alcohol 5j and the corresponding methyl ether 5k, respectively. Preliminary screening of compounds 5a–c in the breast cancer-derived cell line Molt 4 cells indicates that they display similar interesting biological properties as the chromenes3,4 and benzofurans.5,6 The results will be reported elsewhere in due course.We thank the National University of Singapore for a grant in support of this research and for the award of a Research Scholarship to N. S. Techniques used: IR, 1H NMR, mass spectrometry, elemental analysis, flash and thin layer chromatography References: 11 Schemes: 2 Table 1: Analytical, physical and spectral data for compounds 1–3 Table 2: Analytical, physical and spectral data for compounds 4–5 Received, 24th January 1997; Accepted, 12th March 1997 Paper E/7/00565B References cited in this synopsis 1 V. C. Jordan, Pharmacol. Rev., 1984, 36, 245. 2 L. J. Lerner and V. C. Jordan, Cancer Res., 1990, 50, 4177. 3 C. C. Teo, O. L. Kon and K. Y. Sim, J. Chem. Res, 1990, (S) 4; (M) 0171. 4 C. C. Teo and K. Y. Sim, Bull. Singapore Nat. Inst. Chem., 1994, 22, 69. 5 C. C. Teo, O. L. Kon, K. Y. Sim and S. C. Ng, J. Med. Chem., 1992, 35, 1330. 6 S. C. Ng, O. L. Kon, K. Y. Sim and N. Srikanth, Synth. Commun., 1993, 23, 1843. 7 P. Perkin, A. Ray and T. Robinson, J. Chem. Soc., 1926, 941. 8 P. Pfeiffer, E. Breith and H. Hoyer, J. Prakt. Chem., 1931, 237, 31. 9 D. Dhawan and S. K. Grover, Synth. Commun., 1992, 22, 2405. 10 F. A. Luzzio and W. J. Moore, J. Org. Chem., 1993, 58, 2966.

ISSN:0308-2342    

DOI:10.1039/a700565b

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Ni O O H H H H O C O 204 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 204–205 J. Chem. Research (M), 1997, 1344–1358 A Self-assembling Trinuclear Molecular Complex of Nickel(II) with Benzene-1,3,5-tricarboxylic Acid Adonis Michaelides,*a Stavroula Skoulika,a Vangelis Kiritsis,a Catherine Raptopouloub and Aris Terzisb aDepartment of Chemistry, University of Ioannina, 45110 Ioannina, Greece bNRC ‘Demokritos’ Institute of Materials Science, 15310 Aghia Paraskevi Attikis, Greece [Ni3(trim)2(H2O)14] .4H2O (trim=trimesate trianion), a self-complementary molecule organised in tapes using aqua ligands as hydrogen bond donors and carboxylate groups as hydrogen bond acceptors, is synthesised and the structure confirmed by X-ray crystallography.The relative positions of the three carboxylic groups in benzene- 1,3,5-tricarboxylic acid (trimesic acid) make this molecule an interesting multifunctional ligand capable, in principle, of forming infinite metal–organic structures.Coordination polymers with interesting physical properties, based on this ligand have been recently obtained by Yaghi et al.3 and Wood et al.4 However, here we show that [Ni3(trim)2(H2O)14]4H2O (trim\trimesate trianion) 1, is an unusual molecular solid, formed when Ni2+ cations interact with trimesic acid. Crystals suitable for X-ray analysis were formed by using a double diffusion silica gel method.5 An aqueous solution of 0.03 M Ni(NO3)2 was allowed to diffuse in a gel column (pH=6) in contact with a second gel column containing trimesic acid at pH=6.The aqueous phase was allowed to evaporate slowly and well formed green prismatic crystals were collected from the top of the first gel after ca. five months. The stoichiometric formula of the obtained crystals was based on X-ray crystallography. The molecular structure of 1 is shown in Fig. 1. Crystal data for 1. C18H42O30Ni3, triclinic, P�1, a=6.698(3), b=10.771(4), c=12.323(5) Å, a=73.342(9)°, b=77.76(1)°, g=71.76(1)°, V=801.6(6) Å3, Z=1 (the asymmetric unit is half of the molecule), rcalcd=1.895 g cmµ3, l(MoKa)= 0.71073 Å, 3061 independent reflections, 2680 observed [Ia2s(I)], R1=0.0249, wR2=0.0623.R1 is based on f values and wR2 on F2 values. The structure was solved by direct methods using SHELXS-86 and refined by full-matrix leastsquares techniques on F2 with SHELXL-93. Each trimesate anion acts as a bidentate ligand, leaving one carboxylate group free.The two coordinating carboxylate groups bind the metal atoms in a monodentate mode. The ‘central’ Ni2+ atom is located on a crystallographic inversion centre and therefore the three octahedral metal centres are strictly in a straight line 8.036(1) Å apart. Intramolecular hydrogen bonds are observed between coordinated water ligands and the ‘free’ oxygen atoms belonging to the coordinating groups, offering an example of simultaneous first and second coordination spheres.6 At first glance, it is surprising that a molecular solid results from the interaction of Ni2+ with trimesic acid, but inspection of the crystal packing reveals, in our opinion, the reason for this preference (Fig. 2). Each molecule behaves as a selfcomplementary building unit, possessing two hydrogen bond donor [Ni(H2O)2] and two hydrogen bond acceptor (COO) groups, symmetrically disposed. In these conditions, the formation of infinite tapes, by strict self-assembly, through mutual recognition of the complementary groups, seems inevitable7 [Scheme 1(c), see full text].In total, eight hydrogen bonds [OW5...O3=2.637(3), OW6...O4=3.129(3) Å], are used by each molecule for the construction of the tape. To the best of our knowledge, this is the first time that the supramolecular synthon8 has been reported in the literature. The structure is further stabilised by extensive hydrogen bonding, each molecule participating in a total of 46 intermolecular bonds.In this way, *To receive any correspondence. Fig. 1 Molecular structure of 1J. CHEM. RESEARCH (S), 1997 205 each tape is linked to six neighbouring tapes both directly and via bridging lattice water molecules [Fig. 3 (full text)]. The existence of numerous hydrogen bond sites accounts for the solubility of this compound in water and solute– solvent interactions,9 impose a high barrier for nucleation and crystal growth. Crystallisation is certainly due to strong p–p interactions, observed in the direction of the crystallographic a axis (Fig. 3). Each aromatic ring lies between two others with plane-to-plane distances of 3.28 and 3.35 Å and lateral offsets of 1.56 and 2.05 Å, respectively. These hydrophobic interactions decrease the nucleation barrier and lead to successful crystal growth. Techniques used: Crystal growth in gel, X-ray diffraction References: 9 Tables: 5 [Full crystal data, atomic fractional coordinates and U(eq) values, bond distances and angles, geometry of the hydrogen bonds] Figures: 4 (Molecular structure, views of the structure along the a and c axes) Scheme 1: Structures of trimesic acid and 1. Tape molecular arrangement of 1 Received, 20th February 1997; Accepted, 4th March 1997 Paper E/7/01205E References cited in this synopsis 3 O. M. Yaghi, G. Li and H. Li, Nature, 1995, 378, 703. 4 S. O. H. Gutschke, M. Molinier, A. K. Powell, R. E. P. Winpenny and P. T. Wood, Chem. Commun., 1996, 823. 5 A. Michaelides and S. Skoulika, J. Cryst. Growth, 1989, 94, 208. 6 F. M. Raymo and J. F. Stoddart, Chem. Ber., 1996, 129, 981. 7 J.-M. Lehn, Angew. Chem., Int. Ed. Engl., 1990, 29, 1304. 8 G. R. Desiraju, Angew. Chem., Int. Ed. Engl., 1995, 34, 2311. 9 F. Pan, C. Bosshard, M. S. Wong, C. Serbutoviez, S. Follonier, P. Gunter and K. Schenk, J. Cryst. Growth, 1996, 165, 273. Fig. 2 View of an infinite tape along the a axis. Lattice water molecules are omitted for clari

ISSN:0308-2342    

DOI:10.1039/a701205e

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

R1 CHOH R2 R1 C R2 O K2Cr2O7, C6H6–H2O, 70–75 °C, 8 h 1 2 CH3CCl CH Ph p-MeOC6H4 PhCH CH Et Ph H H H H Me Ph a b c d e f 1,2 R1 R2 206 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 206† A New Procedure for the Preparation of Aldehydes and Ketones by the Oxidation of Primary and Secondary Alcohols with Potassium Dichromate in a Neutral Benzene– Water System† Ji-Dong Lou Institute of Materia Medica, Zhejiang Academy of Medicine, Hangzhou, Zhejiang 310013, China A new and convenient procedure for the preparation of aldehydes and ketones by the oxidation of the corresponding primary and secondary alcohols with potassium dichromate in a neutral benzene–water system is described.The oxidation of primary and secondary alcohols to the corresponding aldehydes and ketones is one of the most important reactions in organic chemistry. Potassium dichromate (K2Cr2O7), a readily available and inexpensive reagent, has for some time been used as an oxidant in this reaction.Unfortunately, the traditional K2Cr2O7 oxidation methods in this transformation are limited by the very low solubility of K2Cr2O7 in most organic solvents and by the oxidation procedure occurring only under acidic conditions.1–5 In order to overcome these limitations, milder K2Cr2O7 oxidation methods, such as oxidation under phase-transfer catalysis,6 oxidation with supported reagents7–9 and oxidation in polar aprotic media,10 have been developed that allow the reaction to be conducted in organic media and under neutral conditions.However, even these improved methods possess disadvantages, e.g., the need to use phase-transfer catalysts, the difficulty of preparing the supported reagents, or the use of expensive polar aprotic solvents. We report here a new and convenient procedure for the oxidation of primary and secondary alcohols to the corresponding aldehydes and ketones with K2Cr2O7 in a benzene– water system under neutral conditions.The present method is simpler and more convenient than all the previously improved methods described above, and thus it offers special promise for the oxidation of alcohols with K2Cr2O7 under more usual oxidation conditions. The procedure involves addition of a solution of K2Cr2O7 in water over 30 min to a stirred solution of the alcohol 1 in benzene‡ at about 70–75 °C. After 8 h the benzene layer is separated and the product 2 is isolated. The experimental results are summarized in Table 1.Experimental Typical Procedure: Oxidation of Benzyl Alcohol.·Benzene (100 ml), benzyl alcohol (1b) (10.8 g, 0.1 mol) and water (20 ml) were placed in a flask fitted with a condenser, the mixture was stirred with an electromagnetic stirrer and a solution of potassium dichromate (K2Cr2O7) (29.4 g, 0.1 mol) in water (100 ml) was added over 30 min at 70–75 °C. After the reaction mixture had been maintained between 70 and 75 °C with stirring for a further 8 h, the organic phase was separated.The aqueous phase was extracted with benzene (3Å20 ml) and the extracts were added to the organic phase. The combined organic extracts were washed sequentially with water, saturated sodium hydrogen carbonate solution and water, and dried with magnesium sulfate, and were then distilled through a short Vigreux column to give benzaldehyde (2b) (9.1 g, 86%). Received, 6th January 1997; Accepted, 4th March 1997 Paper E/7/00130D References 1 L. T.Sandborn, Org. Synth., 1941, Coll. Vol. 1, 340. 2 L. F. Fieser, Org. Synth., 1941, Coll. Vol. 1, 383. 3 C. D. Hurd and R. N. Meinert, Org. Synth., 1943, Coll. Vol. 2, 541. 4 D. Pletcher and S. J. D. Taid, Tetrahedron Lett., 1978, 1601. 5 L. Lombardo, Org. Synth., 1987, 65, 81. 6 R. O. Hutchins, N. R. Natale and W. J. Cook, Tetrahedron Lett., 1977, 4167. 7 E. Santaniello and P. Ferraboschi, Nouv. J. Chim., 1980, 4, 279. 8 T. Tatsumi, H. Ohta and H. Tominaga, Nippon Kagaku Kaishi, 1988, 1759 (Chem.Abstr., 1989, 110, 191884p). 9 M. S. Climent, J. M. Marinas and J. V. Sinisterra, React. Kinet. Catal. Lett., 1989, 38, 13 (Chem. Abstr., 1989, 111, 56795r). 10 E. Santaniello, P. Ferraboschi and P. Sozzani, Synthesis, 1980, 646. 11 S. Budavari, The Merck Index, Merck & Co., Rahway, N.J., 11th edn., 1989, p. 166. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). ‡NB. In view of the health and safety hazards of using benzene,11 we have recently investigated, and now recommend, the use of toluene in place of benzene in this two-phase oxidation reaction. Table 1 Oxidation of alcohols 1 Substrate Producta Yield (%)b 1a 1b 1c 1d 1e 1f 2a 2b 2c 2d 2e 2f 92 86 86 90c 68c 90c aAll the aldehydes and ketones have been described previously in the literature and were identified by their IR spectra or by the IR spectra and melting points of their 2,4-dinitrophenylhydrazones. bDistilled product. cIsolated as the 2,4-dinitrophenylhydrazone.

ISSN:0308-2342    

DOI:10.1039/a700130d

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

X 1 X = CHO 2 X = CH2OH O H 3 CHO + • 1 4 FVP Ph O H PhCHO 5 6 J. CHEM. RESEARCH (S), 1997 207 J. Chem. Research (S), 1997, 207† A Short, Convenient Synthesis of Propynal† Hamish McNab,* Gilles Morel and Elizabeth Stevenson Department of Chemistry, The University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK Propynal 1 is obtained in 80% yield on a preparative scale by flash vacuum pyrolysis of diprop-2-ynyl ether 3. Propynal (propargyl aldehyde) 1 is a useful three-carbon reagent which can be made on a large scale by an Organic Syntheses route involving chromium trioxide oxidation of prop-2-ynyl alcohol 2.1 However, this is a low-yielding method (35–41%) with inconvenient work-up due in part to the low boiling point (54–57 °C) of the product.The procedure is particularly awkward if only a small quantity of propynal 1 is required. A more recent variant may be useful for producing a solution of the aldehyde,2 but in our hands3 it proved impossible to separate the product from the mixture of solvents employed, using standard laboratory distillation apparatus.Here we report full experimental conditions for a convenient one-step flash vacuum pyrolysis (FVP) route to pure propynal 1 based on the retro-ene reaction of commercially available diprop-2-ynyl ether 3 (Scheme 1).4 This reaction has been studied previously, but details are not readily available.5,6 An analogous procedure has been used to generate propynethial from diprop-2-ynyl sulfide for in situ photoelectron spectroscopic determination.7 The participation of prop-2-ynyl groups in retro-ene reactions has been widely investigated kinetically6,8,9 and shown to be concerted10 and consistently faster than the reaction of the corresponding allyl derivative.6 FVP of silylated prop-2-ynyl ethers has been used as a preparative route to silylallenes.11 Small-scale (ca. 100 mg) pyrolyses of diprop-2-ynyl ether 3 were successful at 750 °C, generating essentially quantitative yields of propynal 1 [dH 9.16 (1 H, s) and 3.51 (1 H, s)] under these conditions.Significant amounts of starting material were recovered at lower pyrolysis temperatures. Allene 4, the only co-product, was identified by its characteristic singlet at dH 4.62 in the 1H NMR spectrum of the crude pyrolysate. Owing to the volatility of both the precursor and the product, minor design modifications for both the inlet and the trap systems of our standard FVP apparatus were required for successful pyrolyses on a preparative (ca. 2 g) scale (see Experimental section). It is particularly important to ensure that the volatile products do not block the trap, since this leads to an increase in contact time of the precursor in the furnace and causes the formation of a brown polymeric deposit at the exit point. After completion of the pyrolysis, the majority of the allene (bp µ34 °C) evaporates when the trap is allowed to warm to room temperature under an atmosphere of nitrogen.The mobile liquid residue is almost pure propynal 1, and reproducible yields of 80% can be routinely achieved. Gas-phase thermolysis of unsymmetrical prop-2-ynyl ethers to give carbonyl compounds may have more general application in synthesis, and as a simple example we have obtained benzaldehyde 5 (63%) by FVP of benzyl prop- 2-ynyl ether8,12 6 at 750 °C (0.1 Torr). Experimental 1H NMR spectra were recorded at 200 MHz for solutions in [2H]chloroform.Propynal (1).·Diprop-2-ynyl ether4 3 (2.0 g, 21 mmol) was weighed into a round-bottomed flask and connected via a rightangled adaptor to an empty silica furnace tube (35Å2.5 cm) which was maintained at 750 °C by an electrically heated furnace. The exit end of the furnace tube was connected to a U-tube trap of 1.9 cm internal diameter, which was cooled in liquid nitrogen. The inlet flask was cooled in ice, and the whole system was evacuated to a pressure of 10µ2–10µ3 Torr.The ether distilled through the furnace as the ice melted over a period of 40–60 min. If necessary the evaporation was completed by warming the flask in warm (ca. 60 °C) water. If the products blocked the trap, the liquid nitrogen level at the trap was lowered as soon as possible by 1–2 cm to allow the products to melt, flow down the tube and resolidify. The product which remained in the trap after it warmed to room temperature was almost pure propynal 1 (0.92 g, 80%), dH 9.16 (1 H, s) and 3.51 (1 H, s); m/z 54 (33%) and 53 (100), which was sufficiently pure for most synthetic purposes.Benzaldehyde (5).·Benzyl prop-2-ynyl ether12 6 (0.5 g, 4.7 mmol) was distilled at 10µ1 Torr under similar conditions to those described above, into the furnace which was maintained at 750 °C. The sole product in the trap after evaporation of allene was benzaldehyde (0.23 g, 63%), dH 10.02 (1 H, s), 7.88 (2 H, m) and 7.45–7.65 (3 H, m). Received, 20th January 1997; Accepted, 17th March 1997 Paper E/7/00453B References 1 J.C. Sauer, Org. Synth., 1963, Coll. Vol. IV, 813. 2 M. G. Veliev and M. M. Guseinov, Synthesis, 1980, 461. 3 H. McNab, J. Chem. Soc., Perkin Trans. 2, 1981, 1283. 4 Compound 3 can also be readily made in 73% yield by the method of R. E. Geiger, M. Lalonde, H. Stoller and K. Schleich, Helv. Chim. Acta, 1984, 67, 1274. 5 R. A. Malzahn, Ph.D. Dissertation, University of Maryland, 1962, quoted in ref. 6. 6 A. Viola, J. J. Collins and N. Filipp, Tetrahedron, 1981, 37, 3765. 7 O. M. Nefedov, V. A. Korolev, L. Zanathy, B. Solouki and H. Bock, Mendeleev Commun., 1992, 67. 8 H. Kwart, S. F. Sarner and J. Slutsky, J. Am. Chem. Soc., 1973, 96, 5234. 9 H. Kwart, J. Slutsky and S. F. Sarner, J. Am. Chem. Soc., 1973, 96, 5242. 10 A. Viola, G. F. Dudding and R. J. Proverb, J. Am. Chem. Soc., 1977, 99, 7390. 11 H. Hopf and E. Naujoks, Tetrahedron Lett., 1988, 29, 609. 12 A. Manzocchi, A. Fiecchi and E. Santaniello, Synthesis, 1987, 1007. *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Scheme 1

ISSN:0308-2342    

DOI:10.1039/a700453b

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Ph3P + RO2CC CCO2R + O H N H O R¢ Ph3P+ C CHCO2R CO2R O H N– O R¢ H O N CHCO2R O R¢ C CO2R PPh3 2 N CO2R CO2R O R¢ 3 4 1 CH2Cl2 r.t. + a R = Me, R¢ = Me b R = Et, R¢ = Me c R = But, R¢ = Me d R = Me, R¢ = Ph e R = Et, R¢ = Ph f R = But, R¢ = Ph 5 PPh3 208 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 208–209† One-step Synthesis of Dialkyl 1,2-Dihydroquinoline- 2,3-dicarboxylates. A Vinyltriphenylphosphonium Salt Mediated Intramolecular Wittig Reaction† Issa Yavari,* Ali Ramazani and Abbas Ali Esmaili Chemistry Department, Tarbiat Modarres University, P.O.Box 14155-4838, Tehran, Iran Dialkyl 1,2-dihydroquinoline-2,3-dicarboxylates are formed in a one-pot reaction from amide derivatives of 2-aminobenzaldehyde, dialkyl acetylenedicarboxylates and triphenylphosphine in CH2Cl2 in high yields. Quinolines1 are interesting synthetic targets because they act as building blocks for a large number of natural products. In recent years there has been an increase in interest in the synthesis of quinoline compounds.This interest has resulted from the use of such compounds in a variety of biological and synthetic applications.2 While a number of synthetic methodologies for the quinoline ring system have been developed,3 the literature describing a novel one-pot cyclization method based on consecutive processes is rather scarce. Recently, we have established a heterocyclic synthesis using a novel approach to vinylphosphonium salts.4,5 Here we describe a facile one-pot synthesis of dialkyl 1,2-dihydroquinoline- 2,3-dicarboxylates (5) in high yields.Several examples are known in which an unsaturated heterocyclic compound is formed from a phosphorane connected to a carbonyl group by a chain containing a heteroatom. 6–10 Thus, quinoline 5 may be considered as the product of an intramolecular Wittig reaction. Such addition-cyclization products apparently result from the initial addition of triphenylphosphine to the acetylenic ester11,12 and concomitant protonation of the 1:1 adduct, followed by attack of the anion of the 2-aminobenzaldehyde derivative on the vinylphosphonium cation to form the phosphorane 4 which is then converted into quinolines.The essential structures of compounds 5a–f were deduced from their elemental analyses and their 1H and 13C NMR spectra. The molecular ion peak is very weak in the mass spectra of 5a–f accompanied by a stronger M+1 peak owing to the protonation of these molecules in the mass spectrometer.Initial fragmentations involve loss from one of the quinoline side chains. The 1H NMR spectrum of 5a displayed five single lines readily recognizable as arising from methyl (d 2.32), methoxy (d 3.61 and 3.88), N·CH (d 6.62) and olefinic CH (d 7.61) protons, along with a fairly complex multiplet in the aromatic region (see Experimental section). The noise-decoupled 13C NMR spectrum of 5a showed 15 distinct resonances in agreement with the dihydroquinoline structure.Partial assignments of these resonances are given in the Experimental section. The 1H and 13C NMR spectra of 5b–f are similar to those of 5a, except for the ester groups and the amide moiety, which exhibit characteristic signals with appropriate chemical shifts (see Experimental section). The structural assignments made on the basis of the 1H and 13C NMR spectra of compounds 5a–f were supported by measurement of their IR spectra.The carbonyl region of the spectrum exhibited three distinct absorption bands for each compound (see Experimental section). Of special interest is the ester absorption at 1691–1714 cmµ1 for these compounds. Conjugation with the carbon–carbon double bond appears to be a plausible factor in the reduction of these bands.13 In conclusion, vinyltriphenylphosphonium salts have been shown to be useful precursors for a new and efficient synthetic route to 1,2-dihydroquinoline derivatives.The one-pot nature of the present procedure makes it an alternative to multistep approaches.14–16 Further applications of this type of addition-cyclization to the synthesis of interesting heterocycles will be reported in due course. Experimental Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected. Elemental analyses were performed using a Heraeus CHN-O-rapid analyser. IR spectra were recorded on a Shimadzu IR-460 spectrometer. 1H and 13C NMR spectra were measured with JEOL EX-90A spectrometer at 90 and 22.6 MHz, respectively.Mass spectra were recorded on a Finnigan- Matt 8430 mass spectrometer operating at an ionization potential of 70 eV. Preparation of Anilides 2a and 2d.·Compounds 2a and 2d were prepared by known methods17 and identified as follows. 2p- Formylacetanilide 2a: white crystals, mp 68–69 °C. dH (CDCl3) 2.23 (3 H, s, CH3CON), 7.1–7.7 (3 H, m, arom.), 8.71 (1 H, d, J 8.1 Hz, 3-H), 9.88 (1 H, s, CHO), 11.1 (1 H, brs, CONH).dC (CDCl3) 25.00 (CH3), 119.35, 122.49, 135.71 and 135.73 (4 CH), 121.27 (C2), 140.61 (C1), 169.07 (CON), 195.22 (CHO). 2p-Formylbenzanilide 2d: white crystals, mp 70–71 °C. dH (CDCl3) 7.1–8.1 (8 H, m, arom.), 8.94 (1 H, d, J 8.1 Hz, 3-H), 9.96 (1 H, s, CHO), 12.0 (1 H, brs, CONH). dC (CDCl3) 119.27, 122.44, 135.63 and 135.65 (4 CH), 121.43 (C2), 140.57 (C1), 126.96 and 128.35 (2 CH of benzoyl, ortho and meta), 131.65 (CH of benzoyl, para), 133.72 (ipso-C of benzoyl), 165.24 (CON), 195.29 (CHO).*To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M).J. CHEM. RESEARCH (S), 1997 209 Preparation of Dialkyl 1,2-Dihydroquinoline-2,3-dicarboxylates 5.·The typical process, exemplified for the preparation of 5a, is described below. Preparation of 5a. To a magnetically stirred solution of triphenylphosphine (0.262 g, 1 mmol) and 2p-formylacetanilide 2a (0.161 g, 1 mmol) in CH2Cl2 (3 ml) was added dropwise a mixture of dimethyl acetylenedicarboxylate (0.142 g, 1 mmol) in CH2Cl2 (2 ml) at µ10 °C over 10 min.The reaction mixture was then allowed to warm up to room temperature and stirred for 24 h. The solvent was removed under reduced pressure and the residue was purified by silica gel (Merck silica gel 60, 230–400 mesh) column chromatography using diethyl ether–hexane (1:1) as eluent.The solvent was removed under reduced pressure to afford the product (0.26 g, mp 137–138 °C, 90%) which was recrystallized from ethanol (95%) to yield dimethyl N-acetyl-1,2-dihydroquinoline-2,3-dicarboxylate (5a) as white crystals (0.24 g), mp 138–139 °C; vmax/cmµ1 (KBr) 1740 and 1714 (2 C�O, ester), 1668 (C�O, amide); dH (CDCl3) 2.32 (3 H, s, CH3CON), 3.61 and 3.88 (6 H, 2 s, 2 OCH3), 6.62 (1 H, s, NCH), 7.1–7.5 (4 H, m, arom.), 7.61 (1 H, s, 4-H); dC (CDCl3) 22.23 (CH3CON), 51.78 (NCH), 52.29 and 52.69 (2 OCH3), 124.36, 125.87, 129.00, 130.35 and 134.09 (5 CH), 126.03, 127.21 and 136.41 (3 C), 164.88, 169.24 and 169.68 (3 C�O); m/z 290 (3%, MH+, 230 (12%, MH+µCO2µCH4), 188 (100% MH+µCO2CH3µ CH3CO), 128 (27%, MH+µ2CO2CH3µCH3CHO) [Found: C, 63.8; H, 6.1; N, 4.1%.Calc. for C15H15NO5 (289.29): C, 62.28; H, 5.23; N, 4.84%]. Selected data for 5b. White crystals (0.28 g), mp 113–114 °C, yielded 87%; vmax/cmµ1 (KBr) 1735 and 1709 (2 CO�O, ester), 1665 (C�O, amide); dH (CDCl3) 1.12 (3 H, t, J 7.0 Hz, CH3 of ester), 1.37 (3 H, t, J 7.5 Hz, CH3 of ester), 2.33 (3 H, s, CH3CON), 3.80–4.31 (2 H, 2 dq, J 7.0 and µ10.7 Hz, OCH2 of ester), 4.35 (2 H, q, J 7.5 Hz, OCH2 of ester), 6.60 (1 H, s, NCH), 7.1–7.5 (4 H, m, arom.), 7.59 (1 H, sm, 4-H); dC (CDCl3) 13.97 and 14.29 (2 CH3 of 2 Et), 22.36 (CH3 of CH3CON), 52.12 (NCH), 61.24 and 61.65 (2 OCH2), 124.40, 125.75, 128.88, 130.14 and 133.65 (5 CH); 126.15, 127.94 and 136.54 (3 C); 164.51, 168.71 and 169.64 (3 C�O); m/z 318 (2%, MH+), 244 (17%, MH+µCO2Et), 202 (100%, MH+µ CO2EtµCH3CO), 174 (45%,H3COµCO2EtµCH2 �CH2), 128 (25%, MH+µ2CO2EtµCH3CHO) [Found: C, 63.8; H, 6.1; N, 4.1%.Calc. for C17H19NO5 (317.34): C, 64.34; H, 6.04; N, 4.41%]. Selected data for 5c. Viscous colourless oil (0.35 g), yield 94%; vmax/cmµ1 (CCl4) 1732 and 1702 (2 C�O, ester), 1670 (C�O, amide); dH (CDCl3) 1.29 and 1.57 (18 H, 2 s, 2 But), 2.32 (3 H, s, CH3CON), 6.38 (1 H, s, NCH), 7.1–7.4 (4 H, m, arom.), 7.45 (1 H, s, 4-H); dC (CDCl3) 27.81 and 28.18 (6 CH3, 2 But), 52.73 (NCH), 81.48 and 82.30 (2 C, 2 But), 124.36, 125.46, 128.60, 129.82 and 132.30 (5 CH), 126.32, 128.60 and 136.62 (3 C), 163.78, 167.81 and 169.56 (3 C�O); m/z 374 (2%, MH+), 272 (4%, MH+µCO2µ Me3CH), 230 (7%, MH+µCO2ButµCH3CO), 174 (100%, MH+µCO2ButµCH3CO, CH2�CMe2) [Found: C, 68.3; H, 7.3; N, 4.2%.Calc. for C21H27NO5 (373.45): C, 67.54; H, 7.29; N, 3.75%].Selected data for 5d. White crystals (0.29 g), mp 160–161 °C, yield 83%; vmax/cmµ1 (KBr) 1740 and 1705 (2 C�O, ester), 1645 (C�O, amide); dH (CDCl3) 3.63 and 3.89 (6 H, 2 s, 2 OCH3), 6.46 (1 H, s, NCH), 6.7–7.6 (9 H, m, arom.), 7.69 (1 H, s, 4-H); dC (CDCl3) 52.59 and 52.73 (2 OCH3), 53.50 (NCH), 125.01, 125.14, 129.78, 131.04 and 134.22 (5 CH of quinoline), 128.27 and 129.04 (2 CH of benzoyl, ortho and meta), 128.80 (CH of benzoyl, para), 134.30 (ipso-C of benzoyl), 126.37, 129.05 and 137.35 (3 C of quinoline), 164.84, 169.11 and 169.44 (3 C�O); m/z 352 (4%, MH+), 294 (10%, MH+µCO2µCH4), 156 (15%, MH+µCO2CH3µOCH3, C6H5CHO), 128 (20%, MH+µ2 CO2CH3µC6H5CHO) 105 (100%, C6H5CO+) [Found: C, 67.7; H, 4.9; N, 3.6%.Calc. for C20H17NO5 (351.36): C, 68.37; H, 4.88; N, 3.99%]. Selected data for 5e. White crystals (0.33 g), mp 76-5–78 °C, yield 88%; vmax/cmµ1 (KBr) 1730 and 1691 (2 C�O, ester), 1665 (C�O, amide); dH (CDCl3) 1.14 (3 H, t, J 7.2 Hz, CH3 of ester), 1.37 (3 H, t, J 7.0 Hz, CH3 of ester), 3.80–4.31 (2 H, 2 dq, J 7.2 and µ10.8 Hz, OCH2 of ester), 4.35 (2 H, q, J 7.0 Hz, OCH2 of ester), 6.43 (1 H, s, NCH), 6.7–7.6 (9 H, m, arom.), 7.66 (1 H, s, 4-H); dC (CDCl3) 13.93 and 14.29 (2 CH2CH3), 53.51 (NCH), 61.24 and 61.69 (2 OCH2), 125.12, 125.13, 129.66, 131.00 and 134.42 (5 CH of quinoline), 128.31 and 129.04 (2 CH of benzoyl, ortho and meta), 128.72 (CH of benzoyl, para), 133.77 (ipso-C of benzoyl), 127.01, 129.05 and 137.39 (3 C of quinoline), 164.47, 168.62 and 169.56 (3 C�O); m/z 380 (3%, MH+), 306 (100%, MH+µ2 CH2�CH2µH2O), 279 (15%, MH+µCO2EtµCH2�CH2), 105 (C6H5CO+) [Found: C, 69.0; H, 5.7; N, 3.4%.Calc. for C22H21NO5 (379.42): C, 69.65; H, 5.58; N, 3.69%]. Selected data for 5f. White crystals (0.41 g), mp 128.5–130 °C, yield 95%; vmax cmµ1 KBr 1735 and 1699 (2 C�O, ester), 1647 (C�O, amide); dH (CDCl3) 1.32 and 1.56 (18 H, 2 s, 2 But), 6.24 (1 H, s, NCH), 6.7–7.5 (9 H, m, arom.), 7.53 (1 H, s, 4-H).dC (CDCl3) 27.81 and 28.06 (6 CH3, But), 54.28 (NCH), 81.36 and 82.28 (2 C, 2 But), 124.85, 125.05, 129.29, 130.80 and 132.38 (5 CH of quinoline), 128.23 and 128.84 (2 CH of benzoyl, ortho and meta), 128.39 (CH of benzoyl, para), 134.70 (ipso-C of benzoyl), 125.30, 128.85 and 137.35 (3 C of quinoline), 163.62, 167.65 and 169.48 (3 C�O); m/z 436 (2%, MH+), 334 (100%, MH+µCO2µMe3CH), 306 (15%, MH+µ2 CH2�CMe2µH2O), 278 (50%, MH+µCO2 µMe3CHµCH2�CMe2), 156 (10%, MH+µCO2ButµOBut µC6H5CHO), 105 (25%, C6H5CO+), 174 (100%, MH+µ CO2ButµCH3CO, CH2�CMe2 [Found: C, 71.3; H, 6.8; N, 3.4%.Calc. for C26H29NO5 (435.52): C, 71.70; H, 6.71; N, 3.22%]. Received, 3rd December 1996; Accepted, 19th February 1997 Paper E/6/08156H References 1 J. D. Hepworth, in Comprehensive Heterocyclic Chemistry, ed. A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford, 1984, vol. 2, pp. 165–524. 2 R. Albrecht, Progress in Drug Research, ed.E. Jucker, Birkhauser Verlag, Basel, 1977, vol. 21, p. 9. 3 The Chemistry of Heterocyclic Compounds, ed. G. Jones, Wiley, New York, 1982, vol. 32, p. 93; S. Radl and D. Bouzard, Heterocycles, 1992, 34, 2143. 4 I. Yavari, A. Ramazani and A. Yahya-Zadeh, Synth. Commun., 1996, 26, 4495. 5 I. Yavari and A. Ramazani, J. Chem. Res. (S), 1996, 382. 6 K. B. Becker, Tetrahedron, 1980, 36, 1717. 7 I. Burley and A. T. Hewson, Synthesis, 1995, 1151. 8 P. Kumar, C. U. Dinesh and B. Pandey, Tetrahedron Lett., 1994, 35, 9229. 9 E. Zbiral, Synthesis, 1974, 775. 10 K. P. C. Vollhardt, Synthesis, 1975, 765. 11 E. Winterfeldt, Angew. Chem., Int. Ed. Engl., 1967, 6, 423. 12 A. W. Johnson and J. C. Tebby, J. Chem. Soc., 1961, 2126. 13 W. A. Kleschick and C. H. Heathcock, J. Org. Chem., 1978, 43, 1256. 14 E. E. Schweizer and L. D. Smucker, J. Org. Chem., 1966, 1, 3146. 15 K. Akiba, Y. Negishi, K. Kurumaya, N. Ueyama and N. Inamoto, Tetrahedron Lett., 1981, 22, 4977. 16 M. J. Weiss and C. R. Hauser, in Heterocyclic Compounds, ed. R. C. Elderfield, Wiley, New York, 1961, vol. 7, p. 541. 17 L. I. Smith and J. W. Opie, Org. Synth., 1955, Coll. Vol. III, 56; P. E. Fanta and D. S. Tarbell, Org. Synth., 1955, Coll. Vol. III, 661; A. W. Ingersoll and S. H. Babcock,

ISSN:0308-2342    

DOI:10.1039/a608156h

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

210 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 210–211† Conformational Properties of Cyclododeca-1,5,9-triyne† Issa Yavari,*a Avat (Arman) Taherpourb and Arash Jabbarib aChemistry Department, Tarbiat Modarres University, P.O. Box 14155-4838, Tehran, Iran bChemistry Department, Islamic Azad University, P.O. Box 19395-1775, Tehran, Iran Semi-empirical AM1 SCF-MO calculations are used to calculate the structure optimization and conformational interconversion pathways in cyclododeca-1,5,9-triyne; two symmetrical energy-minimum conformations, viz.chair (D3) and twist-boat (C2), with similar strain energies are found which are separated by a fairly low (9.6 kJ molµ1) energy barrier. Cyclododeca-1,5,9-triyne (1), with three acetylenic chromophores alternatively inserted in carbon–carbon bonds of cyclohexane, could experience six-electron cyclic interactions of both the in-plane and out-of-plane p bonds of the three acetylene moieties, and might exhibit homoaromaticity.1 This ‘exploded cyclohexane’ is expected to manifest special conformational properties, since the torsional strain and transannular van der Waals repulsions, which play such a crucial rule in determining the relative energies of the various conformations of cyclohexane, will be greatly reduced.2–4 Ab initio calculations with the STO-3G minimal basis set have been reported1 for the chair-like (D3) and planar D3h geometries of 1.According to these calculations the D3 conformation is 67 kJ molµ1 more stable than D3h.The photoelectron spectrum of 1 has been interpreted in terms of a chair-like conformation of D3 symmetry.1 We present the results of Austin Model 1 (AM1) semiempirical SCF-MO calculations5 on 1 that allow interesting conclusions to be drawn about the conformational properties of this molecule. Two symmetrical energy-minimum conformations, viz. chair (D3) and twist-boat (C2), with similar strain energies6 are found which are separated by a fairly low energy barrier.The planar D3h geometry of 1 was found to be about 26.9 kJ molµ1 less stable than the D3 conformation. Semi-empirical calculations were carried out using the AM1 method with the MOPAC 6.0 program7,8 implemented on a VAX 4000-300 computer. Energy-minimum geometries were located by minimizing energy with respect to all geometrical coordinates, and without imposing any symmetry constraints. The structures of the transition-state geometries were obtained using the optimized geometries of the equilibrium structures according to the procedure of Dewar et al.9 (using keyword SADDLE).All structures were characterized as stationary points, and true local energy-minima and energy-maxima on the potential energy surface were found using the keyword FORCE. All energy-minima and energymaxima geometries obtained in this work are calculated to have 3Nµ6 and 3Nµ7 real vibrational frequencies, respectively. 10 Results and Discussion The results of semi-empirical AM1 calculations for various molecular geometries of cyclododeca-1,5,9-triyne (1) are shown in Table 1 and Fig. 1. The conformational possibilities available to 1 parallel those of cyclohexane.11 Thus, chair and twist-boat conformations should be accessible. The chair conformation, which has D3 symmetry, is calculated to have the lowest heat of formation (DHf°). Since the twist-boat form has a higher (by ca. 2.3 kJ molµ1) DHf than the chair form, it is expected to be significantly populated at room temperature.The chair conformation is the same as the structure determined by photoelectron spectroscopy.1 The energy surface for the interconversion of the energyminimum conformations of 1 was investigated in detail by changing different torsional angles. The results are shown in Fig. 1. There are two distinct, different transition states (not counting mirror images) which are required to describe the conformational dynamics in cyclododeca-1,5,9-triyne. The internal and torsional angles of these transition states are given in Table 1.The simplest conformational process, and the one with the lowest barrier, is the degenerate interconversion of the chair conformation with its mirror image via the twist-boat intermediate. If this process is fast the time-averaged symmetry of the chair conformation becomes D3h, which is the maximum symmetry allowed by the chemical structure of cyclododeca- 1,5,9-triyne.A second, and higher-energy, process undergone by the chair conformation is also degenerate, and involves the planar transition state, which has D3h symmetry. The calculated heat of formation for planar D3h geometry is 26.9 kJ molµ1, which is much higher than those for twist and halfchair geometries (see Table 1). Two significant differences can be anticipated between the conformational features of cyclododeca-1,5,9-triyne (1) and cyclohexane. The first derives from the fact that torsional effects and transannular van der Waals repulsion should diminish in 1, since the dimensions of the ring will be magni- fied while the CH2CH2 groups will remain unchanged in size.Consequently, conformations such as chair and twist-boat should hardly differ in energy from one another. By comparison, cyclohexane exists mainly in the chair conformation (a99%) at room temperature.11 The other conformational feature of 1 concerns its flexibility. The ease with which the C·C�C bond angles can be deformed from linearity and the large number of sp carbon atoms over which angle strain can be spread will practically reduce the barriers to conformational interconversions in 1.*To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Fig. 1 Calculated strain energy (kJ molµ1) profile for the degenerate interconversion of the chair conformation of cyclododeca-1,5,9-triyne with its mirror image geometry via twist-boat intermediatesJ.CHEM. RESEARCH (S), 1997 211 Thus, the barrier separating the chair from the twist-boat conformation should be only a small fraction of the 45 kJ molµ1 required for the same conformational change in cyclohexane.11 In conclusion, AM1 calculations provide a picture of the conformations of cyclododeca-1,5,9-triyne (1) from both the structural and energetic points of view.Compound 1 is predicted to exist as a mixture of chair (D3) and twist-boat (C2) conformations. There is good agreement between the AM1 structure of the chair form and the photoelectron results.1 Received, 31st January 1997; Accepted, 27th February 1997 Paper E/7/00723J References 1 K. N. Houk, R. W. Strozier, C. Santiago, R. W. Gandour and K. P. C. Vollhardt, J. Am. Chem. Soc., 1979, 101, 5183. 2 R.Gleiter, W. Schafer and H. Sakurai, J. Am. Chem. Soc., 1985, 107, 3046. 3 M. J. S. Dewar and M. K. Holloway, J. Chem. Soc., Chem. Commun., 1984, 1188. 4 L. T. Scott, G. J. DeCicco, J. L. Hyun and G. Reinhardt, J. Am. Chem. Soc., 1985, 107, 6546. 5 M. J. S. Dewar, E. G. Zeobisch, E. F. Healy and J. J. P. Stewart, J. Am. Chem. Soc., 1985, 107, 3902; M. J. S. Dewar and K. M. Dieter, J. Am. Chem. Soc., 1986, 108, 8075. 6 E. M. Arnett, J. C. Sanda, J. M. Bollinger and M. Barber, J.Am. Chem. Soc., 1967, 89, 5389. 7 J. J. P. Stewart, J. Comput. Aided Mol. Des., 1990, 4, 1. 8 J. J. P. Stewart, QCPE 581, Department of Chemistry, Indiana University, Bloomington, IN, USA. 9 M. J. S. Dewar, E. F. Healy and J. J. P. Stewart, J. Chem. Soc., Faraday Trans., 1984, 80, 227. 10 J. W. McIver, Acc. Chem. Res., 1974, 7, 72; O. Ermer, Tetrahedron, 1975, 31, 1849. 11 F. A. L. Anet and A. J. R. Bourn, J. Am. Chem. Soc., 1967, 89, 760; M. E. Squillactotte, R. S. Sheridan, O. L. Chapman and F. A. L. Anet, J. Am. Chem. Soc., 1975, 97, 3244. Table 1 Heats of formation, bond angles and dihedral angles for cyclododeca-1,5,9- triyne Chair Twist-boat Twist Half-chair Planar Feature D3 C2 C2 CS D3h DHf°/kJ molµ1 DDHf ° /kJ molµ1 494.5 0.0 496.8 2.3 504.1 9.6 502.6 8.1 521.4 26.9 Bond angle (y/°) y123 y234 y345 y456 y567 y678 y789 y8,9,109,10,11 y10,11,12 y11,12,1 y12,1,2 178 112 112 178 178 112 112 178 178 112 112 178 177 112 113 177 178 113 113 178 177 113 112 177 176 112 113 178 176 116 116 176 178 113 112 176 177 112 113 178 178 115 115 178 178 113 112 177 176 116 116 176 176 116 116 176 176 116 116 176 Dihedral angle (f/°) f2345 f3478 f6789 f7,8,11,12 f10,11,12,1 f11,12,3,4 51 µ69 51 µ69 51 µ69 46 11 µ51 11 46 µ83 49 µ27 0 µ27 49 µ76 50 µ51 0 51 µ50 0 000000 aThe standard strain energy in each geometry of a molecule is defined as the difference between the standard heats of formation (DHf°) for that geometry and the most stable conformation of the molecule.6

ISSN:0308-2342    

DOI:10.1039/a700723j

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N CO2Me CO2Me CO2Me 1 N N X RO2C C C CO2R a b c d X = H X = Me X = Cl X = NO2 2 a b R = Me R = Et 3 N N CO2R CO2R CO2R CO2R CO2R CO2R X a b c d e X = H, R = Me X = H, R = Et X = Me, R = Me X = Cl, R = Me X = NO2, R = Me 4 1 2 3 4 5 6 212 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 212–213† Reaction between 1,10-Phenanthroline and Dialkyl Acetylenedicarboxylates. A Facile Synthetic Route to Helical Dipyrrolophenanthrolines† Issa Yavari,* Malek Taher Maghsoodlou and Ali Pourmossavi Chemistry Department, Tarbiat Modarres University, P.O.Box 14155-4838, Tehran, Iran 1,10-Phenanthroline and its 5-substituted derivatives react with dialkyl acetylenedicarboxylates to give dipyrrolo[1,2- a:2p,1p-k][1,10]phenanthroline derivatives, which exhibit nonplanarity enforced by the crowding of the ester groups. Many diverse products can be prepared from the addition of acetylenic esters to nitrogen-containing heterocycles.1 An example is the interesting reaction between pyridine and dimethyl acetylenedicarboxylate in methanol, in which the indolizine-1,2,3-tricarboxylate (1) is isolated.2–5 However, there appears to be no report of a reaction product formed from 1,10-phenanthroline (2a)6 and acetylenic esters.We have found that 1,10-phenanthrolines 2a–d undergo reaction with dialkyl acetylenedicarboxylates 3a,b to give hitherto unknown dipyrrolo[1,2-a:2p,1p-k][1,10]phenanthroline derivatives 4a–e in moderate yields. The essential structures of compounds 4a–e were deduced from their elemental analyses and their 1H and 13C NMR spectra as well as from the IR spectra which exhibited strong C�O signals.The mass spectra of these compounds displayed molecular ion peaks at m/z 604, 688, 618, 638 and 649 for 4a–e, respectively. Initial fragmentations involve loss of the side chains. The 1H NMR spectrum of 4a exhibited three single sharp lines at d 3.37, 3.99 and 4.03, readily recognizable as arising from methoxy protons, along with two superimposed AB systems and an A2 system for the 1,10-phenanthroline residue in 4a.The 13C NMR spectrum of 4a displayed three signals for the methoxy (d 51.48, 51.95 and 52.78) groups, along with nine signals for the dipyrrolophenanthroline nucleus. The chemical shifts of the ester carbonyl groups at d 158.16, 163.64 and 166.26 are consistent with the symmetrical structure of 4a. The 1H NMR spectrum of compound 4b is analogous to that obtained for 4a, except for the ester groups which exhibited three ABX3 systems (see Table 1) as a result of nonplanarity enforced by the crowding of the ester groups.7 Compounds 4c–e are unsymmetrical and exhibit more complicated, but resolved, 1H and 13C spectra (see Table 1).The structural assignments made on the basis of the NMR spectra of compounds 4a–e were supported by measure- *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Table 1 1H and 13C NMR data for compounds 4a–e Compound 1H/13C d (ppm) (CDCl3–Me4Si) 4a 1H 3.37, 3.99 and 4.03(18 H, 3 s, 6 OCH3), 8.06 (2 H, d, J 9.2 Hz, C2-H and C5-H), 8.10 (2 H, s, C3-H and C4-H), 8.66 (2 H, d, J 9.2 Hz, C1-H and C6-H) 13C 51.48, 51.95 and 52.78 (6 OCH3), 106.44 (2 C), 118.14 (2 CH), 120.07 and 124.82 (4 C), 126.58 (2 CH), 126.92 (2 C), 127.56 (2 CH), 131.08 and 137.62 (4 C), 158.16, 163.64 and 166.26 (6 C�O) 4b 1H 1.166 (6 H, t, J 7.2 Hz, 2 CH3), 1.440 (6 H, t, J 7.2 Hz, 2 CH3), 1.474 (6 H, J 7.2 Hz, 2 CH3), 3.73 and 3.79 (4 H, q of AB system, JAB µ10.8, J 7.2 Hz, 2 CH2), 4.434 and 4.468 (4 H, q of AB system, JAB µ10.8, J 7.2 Hz, 2 CH2), 4.441 and 4.480 (4 H, q of AB system, JAB µ10.7, J 7.2 Hz, CH2), 8.040 (2 H, d, J 9.2 Hz, C2-H and C5-H), 8.070 (2 H, s, C3-H and C4-H), 8.67 (2 H, d, J 9.2 Hz, C1-H and C6-H) 13C 13.80, 14.23 and 14.42 (6 CH3), 60.67, 60.70 and 61.62 (6 CH2), 107.76 (2 C), 118.02 (2 CH), 120.58 and 125.45 (4 C), 126.56 and 127.08 (4 CH), 127.52, 131.25 and 138.12 (6 C), 157.65, 164.10 and 166.06 (6 C�O) 4c 1H 2.95 (3 H, s, CH3), 3.35, 3.38, 3.98, 4.00, 4.04 and 4.05 (18 H, 6 s, 6 OCH3), 7.94 (1 H, s, C4-H), 8.02 and 8.62 (2 H, AB system, J 9.0 Hz, CHCH), 8.24 and 8.68 (2 H, AB system, J 9.2 Hz, CHCH) 13C 19.46 (CH3), 51.35, 51.40, 51.98, 52.00, 52.65 and 52.70 (6 OCH3), 106.50, 106.57, 117.56, 118.09, 119.35, 121.59, 123.18, 123.79, 124.65, 126.19, 126.64, 127.05, 130.07, 130.39, 132.95, 136.82, 136.93, and 138.33 (18 C), 157.43, 157.45, 163.45, 163.48, 165.77 and 165.82 (6 C�O) 4d 1H 3.36, 3.38, 4.00, 4.03, 4.06 and 4.07 (18 H, 6 s, 6 OCH3), 7.97 and 8.67 (2 H, AB system, J 9 Hz, C1-H and C2-H), 8.20 (1 H, s, C4-H), 8.52 and 8.73 (2 H, AB system, J 9.2 Hz, C5-H and C6-H) 13C 51.46, 51.50, 52.02, 52.10, 52.65 and 52.70 (6 OCH3), 107.01, 107.18, 118.62, 118.86, 119.39, 119.56, 123.14, 123.75, 124.93, 125.20, 125.28, 126.19, 125.56, 129.41, 130.43, 130.84, 136.75 and 136.86 (18 C), 157.35, 157.45, 163.16, 163.22, 165.49 and 165.62 (6 C�O) 4e 1H 3.36, 3.39, 4.00, 4.02, 4.05, and 4.06 (18 H, 6 s, 6 OCH3), 8.15 and 8.78 (2 H, AB system, J 9.0 Hz, C1-H and C2-H), 8.82 (1 H, s, C4-H), 8.81 and 8.88 (2 H, AB system, J 9.1 Hz, C1-H and C3-H) 13C 51.46, 51.55, 52.20, 52.25, 52.74 and 52.82 (6 OCH3), 107.67, 107.72, 119.72, 120.00, 120.29, 121.55, 122.49, 122.94, 124.52, 124.89, 126.45, 126.60, 130.12, 131.12, 133.49, 136.21, 137.43 and 143.13 (18 C), 157.06, 157.20, 162.76, 162.84, 164.92 and 165.00 (6 C�O).J.CHEM. RESEARCH (S), 1997 213 ments of their IR and UV spectra. Of special interest is the carbonyl absorption (1698–1748 cmµ1) for these compounds. Conjugation with the heterocyclic ring appears to be a plausible factor in the reduction of the wave numbers of the carbonyl absorption bands.8 The electronic spectra of compounds 4a,b each exhibited bands at 237–340 nm owing to the dipyrrolophenanthroline nucleus.The reactions described herein represent a simple and efficient synthesis of functionalized dipyrrolophenanthrolines. Experimental Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected. Elemental analyses for C, H and N were performed using a Heraeus CHN-O-Rapid analyser. IR spectra were measured on a Shimadzu IR-460 spectrometer.UV spectra were measured using solutions in ethanol (95%) on a Shimadzu UV-2100 spectrometer. 1H and 13C NMR spectra were measured with a JEOL EX-90A spectrometer at 90 and 22.6 MHz, respectively. The 1H NMR spectrum of 4b was recorded at 400 MHz using a Varian Unity Plus NMR spectrometer. Mass spectra were recorded on a Finnigan-Matt 8430 mass spectrometer operating at an ionization potential of 70 eV. 1,10-Phenanthrolines 2a–d and dialkyl acetylenedicarboxylates 3a,b were obtained from Fluka (Buchs, Switzerland) and were used without further purification.Typical preparation of hexamethyl dipyrrolo[1,2-a:2p,1p-k][1,10] phenanthroline-7,8,9,12,13,14-hexacarboxylate (4a).·To a magnetically stirred solution of 1,10-phenanthroline (0.18 g, 1 mmol) in methanol (10 ml) was added dropwise a mixture of dimethyl acetylenedicarboxylate (0.71 g, 5 mmol) in methanol (2 ml) at room temperature and the mixture refluxed for 24 h.After 24 h in a refrigerator at 5 °C, a yellow solid (0.31 g, yield 52%, mp 205–207 °C) was collected by filtration. Recrystallization from methanol yielded 4a as pale yellow crystals (0.28 g), mp 209–211 °C; vmax (KBr)/cmµ1 1745, 1720 and 1698 (C�O); 1240 and 1174 (C·O); lmax/nm (log e) 237 (4.7), 2.8), 289 (3.1), 336 (2.2); MS (m/z, %): 604 (M+, 2), 430 (25), 415 (56), 353 (100), 149 (45), 105 (60) (Found: C, 59.7; H, 4.1; N, 4.7. C30H24N2O12 requires C, 59.61; H, 4.00; N, 4.63%).Selected data for 4b.·Yellow crystals, 0.4 g, yield 58%, mp 183–185 °C; vmax (KBr)/cmµ1 1748, 1741 and 1703 (C�O); 1231 and 1180 (C·O); lmax/nm (log e) 238 (4.5), 270 (2.6), 285 (3.0), 340 (2.5); MS (m/z, %): 688 (M+, 1), 387 (10), 368 (25), 324 (22), 282 (33), 150 (42), 57 (100) (Found: C, 62.1. C36H36N2O12 requires C, 62.83; H, 5.27; N, 4.07%). Selected data for 4c.·Dark-yellow powder, 0.27 g, yield 44%, mp 265 (decomp.); vmax (KBr)/cmµ1 1741, 1735 and 1699 (C�O); 1213 and 1195 (C·O); MS (m/z, %): 619 (M++1, 8), 560 (40), 516 (35), 501 (100), 470 (28), 457 (18), 267 (35) (Found: C, 59.9; H, 4.3; N, 4.7.C31H26N2O12 requires C, 60.20; H, 4.24; N, 4.53%). Selected data for 4d.·Pale yellow powder, 0.26 gm, yield 40%, mp 256 °C (decomp.); vmax(KBr)/cmµ1 1746, 1738 and 1700 (C�O); 1221 and 1174 (C·O); MS (m/z, %): 638 (M+, 15), 579 (25), 535 (38), 520 (100), 489 (35), 286 (82), 149 (42), 144 (76) (Found: C, 56.4; H, 3.7; N, 4.2. C30H23N2O12Cl requires C, 56.39; H, 3.63; N, 4.38%).Selected data for 4e.·Yellow powder, 0.21 g, yield 32%, mp 280 °C (decomp.); vmax (KBr)/cmµ1 1745, 1731 and 1702 (C�O); 1212 and 1168 (C·O); MS (m/z,%): 649 (M+, 5), 590 (12), 546 (55), 531 (100), 485 (26), 310 (38), 251 (42), 149 (90) (Found: C, 55.6; H, 3.6, N, 6.5. C30H23N3O14 requires C, 55.48; H, 3.57; N, 6.47%). Received, 28th February 1997; Accepted, 12th March 1997 Paper E/7/01417A References 1 R. M. Acheson and N. F. Elmore, Adv. Heterocycl. Chem., 1978, 23, 263. 2 R. M. Acheson and J. M. Woollard, J. Chem. Soc. C, 1971, 3296; R. M. Acheson and G. A. Taylor, J. Chem. Soc., 1960, 1691. 3 A. Crabtree, A. W. Johnson and J. C. Tebby, J. Chem. Soc., 1961, 3497. 4 F. J. Swinbourne, J. H. Hunt and G. Klinkert, Adv. Heterocycl. Chem., 1978, 23, 103. 5 W. Flitsh, in Comprehensive Heterocyclic Chemistry, ed. A. R. Katritzky and C. W. Rees, Pergamon, London, 1984, vol. 3, pp. 443–470. 6 L. A. Summers, Adv. Heterocycl. Chem., 1977, 22, 1. 7 E. L. Eliel and S. H. Wilen, Stereochemistry of Organic Compounds, Wiley, New York, 1994, pp. 1163–1166. 8 R. M. Silverstein, G. C. Bassler and T. C. Morril, Spectrometric Identification of Organic Compounds, Wiley, New York, 5th edn., 1991, p

ISSN:0308-2342    

DOI:10.1039/a701417a

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

214 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 214–215† Substituent Constants of the N�CH·NMe2 Group and their Application to the Prediction of the Basicity of Each Site in Bifunctional Amidines† Ewa D. Raczy�nska‡ Institute of General Chemistry, Agricultural University, 02528 Warszawa, Poland Selected s-type values of the N�CH·NMe2 group are estimated and together with literature structure–basicity relationships used to predict the so-called ‘microscopic’ basicity of each site in bifunctional compounds.Structure–reactivity relationships have always attracted the attention of chemists. In 1937 Hammett,1 looking for quantitative models of similarity, proposed eqn. (1), which describes the relationship between the equilibrium or rate constant for substituted (K or k) and unsubstituted (K0 or k0) derivatives in a reaction series, the reaction constant (r) and the substituent constant (s). log K (or k)=log K0 (or k0)+rs (1) The Hammett equation and its modifications have successfully been applied to different reactions of aromatic and aliphatic systems in solution as well as in the gaseous phase.2,3 Depending on the reaction series investigated, different types of s have been proposed,4,5 e.g.s, s0, s+ and sµ, for the description of the total substituent electronic effect, s*, sI, sF for the inductive (field) effect, sR, sR 0, sR +, sR µ for the resonance (mesomeric) effect and sa for the polarizability effect.In the case of amidines, which are interesting because of their high basicity6 and biological activity,7 many structure– basicity relations6,8–14 have been found but only a few s-type values for the amidine group have been proposed.13,15,16 The first estimates of sI and sR 0 for the N�CH·NMe2 group (Table 1) were carried out by Shorter15 on the basis of the 13C chemical shifts obtained for a series of XC6H4N�CH·NMe2 (FDMPs).17 The proposed sI and sR 0 values, when compared with the literature data for the NMe2 group (Table 1), indicate that the CH�N group decreases the effects of the NMe2 group by slightly different factors.For the inductive effect (sI) the transmission factor of the CH�N group is equal to 0.50 and for the resonance effect (sR 0) equal to 0.56. Taking the values of sI (0.03) and sR 0 (µ0.29), the parameters sm 0 and sp 0 can be calculated using the equations sm 0=sI+asR 0 and sp 0=lsI+sR 0, which separate the total electronic effect of the substituent into inductive and resonance effects.4 Values of a=0.21 and l=1.16 for water for FDMPs18 were used.The sm 0 (µ0.03) and sp 0 (µ0.255) values obtained this way are almost the same as those found from the free v(OH) bond observed for FDMP (X=4-OH and 3-OH) and phenols:16 sm 0=µ0.05�0.1 and sp 0=µ0.25�0.1 (Table 1). The s0 values for the N�CH·NMe2 group are smaller than those for the NMe2 group.4,5 This means that the N�CH·NMe2 group is less electron-donating than the NMe2 group.The same behaviour is found for the sp + (µ1.1) value estimated on the basis of the stretching vibration of the C�O group for FDMP (X=4-COMe) and acetophenones (Table 1).13 Exceptions are found for the so called ‘push–pull’ molecules19,20 in which the amidine group is directly linked with a strong electron-accepting group. IR results obtained for N�C·N�CH·NMe2 and N�C·N�C(N�CH· NMe2)2 suggest that the N�CH·NMe2 group is more electron- donating to the resonance effect than the NMe2 group.The effective polarizability (ad) calculated for the N�CH·NMe2 and NMe2 groups from the equation proposed by Gasteiger and Hutchings21 and the literature5 value for sa(NMe2) are used for estimating the sa(N�CH·NMe2). The obtained results (ad=2.89, sa=µ0.40) when compared with those for the NMe2 group (ad=3.15, sa=µ0.44) show a slightly smaller polarizability of the N�CH·NMe2 group (Table 1). For the field effect described by sF, the transmission factor (0.50) of the CH�N group obtained from comparison of sI(N�CH·NMe2) and sI(NMe2) is used.Taking the literature5 value for sF(NMe2) we obtained sF(N�CH·NMe2)=0.05 (Table 1). The sa and sF values for the (CH2)nN�CH·NMe2 group (n=2 or 3) estimated in the same way as those for the N�CH·NMe2 group, and the literature11 values for sa and sF for the (CH2)nNMe2 group are also given in Table 1. The s value obtained for the N�CH·NMe2 group (Table 1) and the literature4,5 value for s(X) can be used to predict the so-called ‘microscopic’ basicities10 corresponding †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). ‡Email: raczynskae@delta.sggw.waw.pl Table 1 Comparison of the s values for amidine and amine groups Group sI µsR 0 µsp 0 µsm 0 µsp + sF µsa N�CH·NMe2 0.03a 0.29a 0.255 b 0.03b 1.0b 0.05b 0.40b 0.25d 0.05d NMe2 0.06e 0.52e 0.32e 0.10e 1.7e 0.10f 0.44f (CH2)2N�CH·NMe2 (CH2)2NMe2 0.015 b 0.03g 0.52b 0.57g (CH2)3N�CH·NMe2 (CH2)3NMe2 0.005 b 0.01g 0.54b 0.59g aRef. 15. bThis work. cRef. 13. dRef. 16. eRef. 4. fRef. 5. gRef. 11. Table 2 ‘Microscopic’a and ‘macroscopic’ (measured) gas phaseb (GB) and hydrogen bondingc (log KHB) basicities for the dibasic compounds: X·N�CH·NMe2 GB X N�CH·NMe2 X Measured NMe2 (CH2)2NMe2 (CH2)3NMe2 OMe (CH2)2OMe 4-C6H4NMe2 4-C6H4OMe 4-C6H4CN 943 961 966 904 952 977 959 917 901 919 922 750 850 890 750 830 951 982 997 908 972 975 961 917.5 log KHB X N�CH·NMe2 X Measured NMe2 (CH2)2OMe CN (CH2)2CN 4-C6H4COMe 4-C6H4CN 4-C6H4NO2 2.2 2.3 s0.5 2.0 1.5 1.3 1.2 s2.0 1.2 2.1 1.1 1.7 1.2 0.6 2.43 2.75 2.10 2.15 1.84 1.49 1.28 aSee in text.bRefs. 11, 12 and 23. cRefs. 13, 14 and 19.Me2N N (CH2) n H X¢ + Me2N N (CH2) n H X¢ OR J. CHEM. RESEARCH (S), 1997 215 to the basicity of the individual functional groups in the bifunctional XN�CH·NMe2 with basic sites in the amidine and X groups (Table 2). For the gas-phase basicity (GB) prediction of the amidine group in XN�CH·NMe2, linear structure–basicity relationships found previously for the monofunctional RN�CH·NMe2 (FDMs) [eqns.(5) and (8b) for alkyl and aryl FDMs from refs. 11 and 12, respectively] and the corresponding s(X) values are applied. The relationships obtained for the series of RNMe2 [eqn. (8f ) from ref. 11] and the s(N�CH·NMe2) values used to estimate the GB(X) in Me2N(CH2)nN�CH·NMe2.For MeO(CH2)2N�CH· NMe2, no equation is used and the estimation of the GB(X) is made on the basic of the literature data for ethers24 containing a similar number of carbon atoms as the bifunctional amidine. For other derivatives the GB(X) values calculated previously by an AM1 method12,22 are given in Table 2. For the estimation of the log KHB(N�CH·NMe2) in XN�CH·NMe2 in CCl4 equations log KHB=2.70µ4.58sF and log KHB=1.95µ0.90s0 found for the alkyl and aryl FDMs on the basis of literature data,13,14 together with the sF(X) and s0(X) values,4,5 were applied.An exception is N�C–N�CH·NMe2 for which the log KHB vs. Dv(OH) relationship and the value of Dv(OH) for the N�CH·NMe2 group, equal to that for the CN group,19 are used. The log KHB vs. Dv(OH) relationships obtained for the series of amines, ethers, nitriles and ketones25,26 and the Dv(OH) values for the NMe2, OMe, CN and COMe groups found for bifunctional amidines13,14 are used in estimating log KHB(X).For the NO2 group log KHB is estimated according to eqn. (7) from ref. 27. The ‘microscopic’ and measured basicities are given in Table 2. The results obtained confirm that in the gas phase (as in solution) the amidine group is more basic (by 40–200 kJ molµ1) than the basic group in X (Table 2) and is protonatecules.22. The hydrogen bond in the non-polar solvent CCl4 is preferentially formed with an electron-accepting group only for so called ‘push–pull’ molecules (e.g.for X=CN).19,20 When both groups are separated by the phenyl ring their hydrogen bonding basicities are of the same order of magnitude (e.g. for X=4-C6H4COMe and 4-C6H4CN).13 An exception is the nitro group for which a very weak hydrogen-bond basicity is observed. Separation by the (CH2)n group eliminates the ‘push–pull’ effect and a hydrogen bond is preferentially formed with the amidine group [e.g.for X=(CH2)2OMe and (CH2)2CN].14 Compounds with flexible conformation are interesting cases: Xp(CH2)nN�CH·NMe2 containing the OMe or NMe2 group, with n=0, 2 or 3, for which the measured basicities in the gas phase (GB) as well as in non-polar solvents (log KHB) are higher than these predicted for the amidine group (Table 2). In the gas phase this may result from proton ‘internal solvation’ by two basic groups, the amidine and Xp groups.23 In a non-polar solvent the formation of a three-centred complex is possible.In such a complex a hydrogen bond may be formed between ROH and two basic sites, the amidine group and the Xp substituent. Proton chelation by two basic groups increases the gasphase basicity of bidentate ligands by 8, 22 and 31 kJ molµ1 for derivatives with Xp=NMe2 and n=0, 2, 3, and by 4 and 20 kJ molµ1 for Xp=OMe and n=0, 2, respectively. The formation of a three-centred complex increases the hydrogen bonding basicity by ca. 0.4 log KHB units for derivatives with X=OMe and n=2. In conclusion the application of s together with the structure –basicity relationships in the prediction of ‘microscopic’ basicities for individual sites in bifunctional (or generally polyfunctional) compounds enables the explanation and estimation of additional effects, e.g. ‘internal’ solvation or the formation of a three-centred complex. I thank the Polish State Committee for Scientific Research for financial support.Received, 12th November 1996; Accepted, 12th March 1997 Paper E/6/07685H References 1 L. P. Hammett, J. Am. Chem. Soc., 1937, 59, 96. 2 J. Shorter, in Similarity Models in Organic Chemistry, Biochemistry and Related Fields, ed. R. I. Zalewski, T. M. Krygowski and J. Shorter, Elsevier, Amsterdam, 1991, ch. 2. 3 R. W. Taft and R. W. Topsom, Prog. Phys. Org. Chem., 1983, 14, 247. 4 O. Exner, in Correlation Analysis in Chemistry: Recent Advances, ed.N. B. Chapman and J. Shorter, Plenum Press, London, 1978, ch. 10. 5 C. Hansch, A. Leo and R. W. Taft, Chem. Rev., 1991, 91, 165. 6 G. H�afelinger and F. K. H. Kuske, in The Chemistry of Amidines and Imidates, ed. S. Patai and Z. Rappoport, Wiley, London, 1991, vol. 2, ch. 1. 7 R. J. Graut, in The Chemistry of Amidines and Imidates, ed. S. Patai, Wiley, New York, 1975, vol. 1, ch. 6. 8 J. Oszczapowicz, in The Chemisry of Amidines and Imidates, ed. S. Patai and Z. Rappoport, Wiley, London, 1991, vol. 2, ch. 12. 9 E. D. Raczy�nska, Pol. J. Chem., 1993, 67, 1145. 10 M. Borgarello, R. Houriet, E. D. Raczy�nska and T. Drapal/a, J. Org. Chem., 1990, 55, 38. 11 E. D. Raczy�nska, P.-C. Maria, J.-F. Gal and M. Decouzon, J. Org. Chem., 1992, 57, 5730. 12 R. W. Taft, E. D. Raczy�nska, P.-C. Maria, I. Leito, J.-F. Gal, M. Decouzon, T. Drapal/a and F. Anvia, Pol. J. Chem., 1995, 69, 41 and references cited therein. 13 E. D. Raczy�nska, C. Laurence and P. Nicolet, J.Chem. Soc., Perkin Trans. 2, 1988, 1491. 14 E. D. Raczy�nska, C. Laurence and M. Berthelot, Can. J. Chem., 1992, 70, 2203. 15 J. Shorter, in The Chemistry of Amidines and Imidates, ed. S. Patai and Z. Rappoport, Wiley, London, 1991, vol. 2, ch. 13. 16 E. D. Raczy�nska and T. Drapal/a, J. Chem. Res., 1993, (S) 54; (M) 0301. 17 J. Oszczapowicz, E. D. Raczy�nska and J. Osek, Magn. Reson. Chem., 1986, 24, 9. 18 E. D. Raczy�nska, Collect. Czech. Chem. Commun., 1992, 57, 113. 19 C. Laurence, M. Berthelot, E. D. Raczy�nska, J.-Y. LeQuestel, G. Duguay and P. Hudhomme, J. Chem. Res. (S), 1990, 250. 20 T. M. Krygowski, R. Anulewicz, E. D. Raczy�nska and C. Laurence, J. Phys. Org. Chem., 1991, 4, 689. 21 J. Gasteiger and M. G. Hutchings, J. Am. Chem. Soc., 1984, 106, 6489. 22 J.-F. Gal, I. Leito, P.-C. Maria, E. D. Raczy�nska, R. W. Taft and F. Anvia, J. Chim. Phys., 1995, 92, 22 and references cited therein. 23 E. D. Raczy�nska, P.-C. Maria, J.-F. Gal and M. Decouzon, J. Phys. Org. Chem., 1994, 7, 725. 24 S. G. Lias, J. F. Liebman and R. D. Levin, J. Phys. Chem. Ref. Data., 1984, 13, 695. 25 M. Helbert, PhD Thesis, University of Nantes, 1990. 26 M. Berthelot, M. Helbert, C. Laurence and J.-Y. Le Questel, J. Phys. Org. Chem., 1993, 6, 302. 27 C. Laurence, M. Berthelot, M. Lucon and D. G. Morris, J. Chem. Soc

ISSN:0308-2342    

DOI:10.1039/a607685h

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

216 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 216–217† Quantum Chemical Study of the Hydrogen-bonded C4H2...HCl Complex† Asit Kumar Chandra* and Minh Tho Nguyen Laboratory of Quantum Chemistry, Department of Chemistry, University of Leuven, Celestijnenlaan 200F, B-3001 Heverlee, Belgium Ab initio molecular orbital calculations at the MP2 full level and density functional calculations using 6-31++G(d,p) basis functions are performed on the C4H2 ...HCl system and it is observed that formation of a weak complex is possible with a p...HCl type hydrogen bond between the C4H2 and HCl molecules.The traditional view of H-bonding interactions has been expanded to include many weak interactions.1–3 Significant among these is the interaction of hydrogen halides with systems having p-electrons (e.g. C2H2 ...HX). The XH...p interaction is also important in the context of crystal engineering and molecular recognition.4,5 The p-electron rich system behaves as an electron donor in these complexes. Theoretical studies play an important role because it is often not possible to determine precisely the minimum energy structure from the experiment alone, particularly when there are many possible forms of the complexes with comparable energies.The purpose of the present communication is to predict the structure and energetics of the hitherto unknown weak hydrogenbonded complex between C4H2 and HCl molecules. To the best of our knowledge, there is no reported experimental or theoretical study on this system and thus we feel the present calculation will be useful for providing basic information on this complex.Method The geometries of the molecules C4H2 and HCl and of the complexes were fully optimised at the MP2=full level and also with density functional theory (DFT) calculations using B3LYP6,7 and B3PW918 exchange-correlation (XC) functionals. 6-31++G(d,p) basis set was used for all the calculations.The DFT calculations with B3LYP and B3PW91 XC functionals are henceforth simply referred to as B3LYP and B3PW91. The Gaussian-94 program package9 was used for all the calculations involving DFT whereas the HONDO program package was used for the MP2 calculations. Harmonic vibrational frequencies are calculated at the MP2 level and DFT with B3LYMP. Results and Discussion We have already mentioned that to the best of our knowledge there is no reported experimental evidence for the complex between C4H2 and HCl.Recently, Chandra et al.10 reported a theoretical study on the C4H2 ...HF complex at the MP2 level of theory.10 It was observed from the theoretical calculations that the most stable complex between diacetylene and HF forms when the H-atom of HF interacts with the p-electron cloud of diacetylene (Lp complex). A weak sigma complex is another possibility in which the acidic hydrogen atom of the diacetylene forms a hydrogen bond with the fluorine atom of HF.It was not possible, however, to separate these two possible forms from the experimental results.11 In the case of HCl, we observed that the sigma complex is very weak and the interaction energy is only 0.1 kcal at the MP2 level. The p complex (Fig. 1) was found to be the most stable complex between C4H2 and HCl and optimisations were carried out both at the MP2 level and at the B3LYP and B3PW91 levels for this complex. The results obtained are summarised in Tables 1 and 2.It is evident from Table 1 that the monomer geometries do not change significantly upon complex formation. This indicates that the stability and structure of the complex are determined predominantly by longrange electrostatic interactions. The importance of electrostatic interactions for determining the structure of the H-bonded complex was emphasized earlier by Buckingham and Fowler.12 However, small increments in the C�C (at which H-bonding takes place) and H·Cl bond lengths have been observed in the complex. Although individual bond lengths are different at MP2 and DFT the increments observed are nearly the same.The hydrogen bond length (Rh, the distance between the centre of the C�C bond and the hydrogen atom of HCl) increases and the dissociation energy decreases when going from MP2 to B3LYP and B3PW91 levels. The geometrical parameters obtained from B3LYP and B3PW91 are almost identical but the dissociation energy decreases from B3LYP to B3PW91.It should be pointed out that methods using finite basis expansions suffer from the basis set superposition error (BSSE). However, in view of the quality of the basis set used in the present calculations, we did not perform any BSSE corrections. Moreover, the BSSE correction by the counterpoise method has been questioned many times13,14 and it has been argued that it overcorrects the BSSE. The hydrogen bond length Rh obtained for the C4H2 ...HCl complex is larger when compared to the corresponding HF complex and/or the HCl complex with acetylene. 10,15 For example, the hydrogen bond lengths obtained *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Fig. 1 Schematic diagram of the diacetylene complexes with HCl Table 1 The optimised geometrical parameters of the C4H2–HCl complex.Values in parentheses correspond to isolated molecules. R/Å MP2 B3LYP B3PW91 H·Cl C·C C·H C�C C�Ca Rh 1.274 (1.269) 1.373 (1.372) 1.064 (1.063) 1.226 (1.225) 1.228 (1.225) 2.439 1.294 (1.287) 1.369 (1.369) 1.067 (1.066) 1.214 (1.214) 1.216 (1.214) 2.468 1.292 (1.283) 1.367 (1.367) 1.068 (1.066) 1.214 (1.214) 1.216 (1.214) 2.481 aC�C bond involved in the hydrogen bonding. Table 2 Total energies (a.u.) at the stationary points, binding energies and dipole moments of the C4H2–HCl complex.Values in parentheses indicate the binding energies after zero point energy correction Method C4H2 HCl C4H2–HCl DE/kcal molµ1 m/Da MP2 B3LYP B3PW91 µ153.03773 µ153.49587 µ153.42427 µ460.21853 µ460.80328 µ460.74973 µ613.25978 µ614.30212 µ614.17662 2.20 (1.31) 1.87 (1.05) 1.65 (0.83) 2.02 2.11 2.16 aDipole moments of HCl obtained from the MP2, B3LYP and B3PW91 calculations are 1.45, 1.46 and 1.49 D respectively.J. CHEM. RESEARCH (S), 1997 217 at the MP2 level are 2.22 and 2.43 Å for the HF and HCl complexes of C4H2 respectively, which is, of course, expected from the strength of the hydrogen bond.The rotational constants calculated from the B3LYP optimised geometry are 5920.17, 1303.02 and 1067.96 MHz. The dipole moments of the complex obtained from MP2, B3LYP and B3PW91 calculations are 2.02, 2.11 and 2.16 D, respectively. Considering the dipole moments of the isolated HCl molecule, it is clear that complex formation between C4H2 and HCl introduces a significant amount of induced dipole moment in the system.The magnitude of the induced dipole moment is nearly the same as that in the C2H2 ...HCl complex.15 A low frequency shift, compared to the isolated molecule values, of the intramolecular hydrogen chloride stretching vibration was observed from the MP2 and DFT calculations (see Table 3). The magnitude of the shifts are 69 and 99 cmµ1 at the MP2 and B3LYP levels, respectively. The p...HCl hydrogen bond is weaker in the diacetylene complex compared to the corresponding acetylene complex and thus a smaller frequency shift of HCl in the diacetylene complex is expected. The same trend was observed from the present theoretical calculations.The HCl frequency shifts observed at the MP2 level for the C2H2 ...HCl and C4H2 ...HCl are 73 and 69 cmµ1, respectively and with B3LYP 126 and 99 cmµ1, respectively. Bearing in mind the strength of the hydrogen bond, it seems that the B3LYP level estimates vibrational frequencies more accurately than the MP2 level.Recently Geerlings and co-workers also made the same observation.16 The intermolecular vibrational frequencies for the C4H2 ...HCl complex are given in Table 4. Intermolecular stretching vibrational frequencies obtained from the B3LYP calfor the C4H2 and C2H2 complexes with HCl are 80 and 93 cmµ1, respectively, which is, of course, expected from the strength of the hydrogen bond of the two complexes.Fig. 2 shows the intermolecular potential curves for the C4H2 ...HCl complex. The variation of the dipole moments of the C4H2 ...HCl complex and isolated HCl with the change in HCl bond length are presented in Fig. 3 which shows that the dipole moment changes more rapidly for the complex. It is, therefore, expected that the intensity of the H·Cl stretching vibration will be increased upon complex formation with diacetylene. Conclusion It has been observed from MP2 and DFT calculations with B3LYP and B3PW91 XC functionals that the formation of a weak molecular complex is possible between diacetylene and HCl with a p...HCl type hydrogen bond.The hydrogen bond lengths obtained from MP2, B3LYP and B3PW91 are 2.439, 2.468 and 2.481 Å, respectively. The binding energy of the C4H2 ...HCl complex should be around 1 kcal molµ1 and the intensity of the H·Cl stretching vibration should increase upon complex formation. The authors are grateful to the Fund for Scientific Research (F.W. O.-Vlaanderen) for financial support. Received, 23rd December 1996; Accepted, 24th February 1997; Paper E/6/08549K References 1 A. C. Legon and D. J. Millen, Chem. Rev., 1986, 86, 635. 2 P. Hobza and R. Zahradnik, Chem. Rev., 1988, 88, 871. 3 J. J. Dannenberg and R. Rios, J. Phys. Chem., 1994, 98, 6714. 4 G. A. Jeffrey and W. Saenger, Hydrogen Bonding in Biological Structures, Springer, Berlin, 1991. 5 G. R. Desiraju, Crystal Engineering: The Design of Organic Solids, Elsevier, Amsterdam, 1989. 6 C. Lee, W. Yang and R. G. Parr, Phys. Rev. B, 1988, 37, 785. 7 A. D. Becke, J. Chem. Phys., 1993, 98, 5648. 8 J. P. Perdew and Y. Wang, Phys. Rev. B, 1992, 45, 13244. 9 Gaussian 94, Revision C.3, M. J. Frisch, G. W. Trucks, H. B. Schlegel, P. M. W. Gill, B. G. Johnson, M. A. Robb, J. R. Cheeseman, T. Keith, G. A. Petersson, J. A. Montgomery, K. Raghavachari, M. A. Al-Laham, V. G. Zakrzewski, J. V. Ortiz, J.B. Foresman, J. Cioslowski, B. B. Stefanov, A. Nanayakkara, M. Challacombe, C. Y. Peng, P. Y. Ayala, W. Chen, M. W. Wong, J. L. Andres, E. S. Replogle, R. Gomperts, R. L. Martin, D. J. Fox, J. S. Binkley, D. J. Defrees, J. Baker, J. P. Stewart, M. Head-Gordon, C. Gonzalez and J. A. Pople, Gaussian Inc., Pittsburgh, PA, 1995. 10 A. K. Chandra, S. Pal, A. C. Limaye and S. R. Gadre, Chem. Phys. Lett., 1995, 247, 95. 11 K. O. Patten and L. Andrews, J. Phys. Chem., 1986, 90, 3910. 12 A. D. Buckingham and P. W. Fowler, Can. J. Chem., 1985, 63, 2018. 13 M. J. Frisch, J. E. Del Bene, J. S. Binkley and H. F. Schaeffer III, J. Chem. Phys., 1986, 84, 2279. 14 D. W. Schwenke and D. G. Truhlar, J. Chem. Phys., 1985, 82, 2418. 15 A. K. Chandra and M. T. Nguyen, unpublished results. 16 F. D. Proft, J. M. L. Martin and P. Geerlings, Chem. Phys. Lett., 1996, 250, 393. 17 S. A. McDonald, G. L. Johnson, B. W. Keelan and L. Andrews, J. Am. Chem. Soc., 1980, 102, 2892. Fig. 2 Intermolecular potential curves for the C4H2 ...HCl complex calculated at MP2 level with 6-31++G(d,p) basis set Fig. 3 Variation of dipole moment with the change in H·Cl bond length from the equilibrium value, in (I) the C4H2 ...HCl complex and (II) isolated HCl Table 3 Hydrogen halide vibrational frequencies and low frequency complex shifts (v/cmµ1) MP2 B3LYP Expt.a Molecule HCl 3120 2949 2888 C4H2–HCl 3051 2850 Shift 69 99 aRef.17. Table 4 Intermolecular harmonic frequencies for C4H2–HCl (cmµ1) Method Stretch In-plane Out-of-plane MP2 B3LYP 101 80 28 31 293 298 234 244

ISSN:0308-2342    

DOI:10.1039/a608549k

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

CO2Me O2N C OMe O O2N C OH O O2N C N O OBn H O2N C N O OBn R H2N C N O O2N-Me + OH R O2N C N O i 1 ii 3 3 3'a OTr H 3 2 O2N C N O 3 3a 3b–d 3 3 4'a OH H 3 4a–d iii iii' iv v' v a R = H b R = Me c R = Bun d R = n-C8H17 218 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 218–219† Phase-transfer-catalysed Preparation of N-Alkylated Trihydroxamic Acids† Pascal Hoffmann, Jean-Baptiste Doucet, Wenhao Li, Laurent Vergnes and Serge Labidalle* Laboratoire de Synth`ese, Physico-Chimie et Radiobiologie, JE 175, Universit�e Paul Sabatier, Facult�e des Sciences Pharmaceutiques, 35, chemin des Mara�ýchers, 31062 Toulouse cedex 04, France We describe a synthetic route involving phase transfer catalysis leading to a series of tripodal N-alkylated hydroxamic acids as models of desferrioxamine; iron(III) exchange reactions between their iron complexes and EDTA were investigated.Naturally occurring hydroxamic acids act variously as growth factors, antibiotics, tumour inhibitors, cell division factors or lipoxygenase inhibitors, and play a major role as iron transfer agents.1 Most of these biological activities are due to their complexing properties towards transition metal ions, particularly with iron(III).Desferrioxamine, a natural trihydroxamic acid, is used therapeutically for the treatment of iron-overloaded patients,2 particularly in patients with AIDS, but the lack of oral activity and its short biological half-life limits its use.Otherwise, iron chelation by desferrioxamine, and other chelators, protects against the cytotoxic and reactivating effects of hydrogen peroxide,3 and thus decreases NF-kB activation due to oxidative stress, and subsequent activation of HIV-1 transcription. The natural products with an iron(III)trihydroxamate centre form a class comprised of many known members. When three hydroxamate functions are present in the same molecule with an appropriate spacing between the hydroxamic acid units, the complex tends to retain the 1:1 structure, even at low pH.In this work, we report the synthesis of a series of N-H or N-alkylated tripodal hydroxamic acids 4 (Scheme 1) as simple models of desferrioxamine. We use phase transfer catalysis4 (PTC) on the one hand to access the triester 1, and on the other hand to perform the N-alkylation reactions. The relative stabilities of the iron(III) complexes were investigated. PTC was used for the first step to synthesize the triester 1, a building block that is often used as a starting material for dendrimeric macromolecule synthesis.5 Michael-type addition of nitromethane to methyl acrylate, without added organic solvent but in the presence of potassium carbonate and with benzyltriethylammonium chloride as phase-transfer reagent, followed by saponification of the triester 1 afforded the triacid 2.Condensation of O-protected hydroxylamines with the triacid chloride gave the O-benzylated trihydroxamic acid 3a, and the O-tritylated trihydroxamic acid 3pa.As the deprotection conditions of the benzyl group are often incompatible with the presence of other functional groups, we used two different protective groups for the synthesis of compounds 3. Although synthetic methods for hydroxamic acids are well documented,6 direct acylation of O-protected hydroxylamine derivatives with acid chlorides remains the most commonly used method. A direct condensation with unprotected hydroxylamine gave a mixture of N- and Oacylated products.Hydroxamic acids have been alkylated with a large variety of electrophiles. Phase-transfer catalysis in the N-alkylation of organic molecules seems to be effective especially when the nitrogen atom has a low basicity which renders it less reactive towards alkylating agents. Here, we used PTC in the absence of solvent for the N-alkylation4c of 3a with methyl iodide, n-butyl bromide, and n-octyl bromide in the presence of potassium tert-butoxide and Aliquat 336 (tricaprylylmethylammonium chloride) to yield respectively the N-alkylated-O-protected hydroxamic acids 3b–d.Finally, deprotection of the benzylated derivatives 3a–d by catalytic hydrogenation with ammonium formate and 10% palladium –carbon gave the amino hydroxamic acids 4a–d in moderate yields (20–35%), while removal of the trityl group of compounds 3pa in acidic diethyl ether gave the nitro derivative 4pa. The N-n-octylated product (4d) was isolated by chromatography on silica gel, whereas 4a–c and 4pa were purified by reversed-phase preparative TLC with a mixture of methanol and water as eluent.All final hydroxamic acids gave a deep red colour in the presence of Fe3+ with a wide characteristic absorption band in the visible range with a maximum located between 420 and 440 nm. In order to investigate the relative stabilities of the iron complexes, the pseudo-first-order constants for iron(III) *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Scheme 1 Reagents and conditions: i, PTC: benzyltriethylammonium chloride, K2CO3, RT; ii, NaOH–methanol, reflux; iii, SOCl2, reflux; O-benzylhydroxylamine, Et3N–THF, RT; iiip, SOCl2, reflux; O-tritylhydroxylamine, Et3N–THF, RT; iv, PTC: methyl iodide, n-butyl bromide or n-octyl bromide, Aliquat 336, potassium tert-butoxide, 50 °C (reflux for methyl iodide, 42 °C); v, ammonium formate, 10% Pd/C– methanol, reflux; vp, HCl–diethyl ether, RT (RT=room temperature)J.CHEM. RESEARCH (S), 1997 219 exchange reactions between the FeIII–4 complexes and EDTA were determined by following the decrease in absorbance at 425 nm in the presence of a large excess of EDTA. The relative stability constants of the iron(III) complexes of 4pa, 4a, 4b, 4c and 4d were respectively 0.8Å10µ2, 1.5Å10µ2, 1.0Å10µ2, 0.2Å10µ2 and 0.4Å10µ2 sµ1, suggesting that the lipophilic compounds 4c and 4d hold iron a little more tightly than do the other ligands.However, the order of magnitude of the observed constants indicates that the tripodal ligands 4 form much less stable complexes than does desferrioxamine, a linear trihydroxamic acid that has an optimal nine-atom spacing between hydroxamate moieties, and whose exchange constant towards EDTA is 6.5Å1µ6 sµ1 under the same experimental conditions.The shape of the molecule (linear or tripodal) and the spacing between the hydroxamic acid units seem to play a major role in creating stable iron(III) complexes. The final hydroxamic acids will be tested as potent antiviral agents in future work; moreover, as part of a program to develop novel chelators for the radioimaging of organs and tumours, the affinity of the trihydroxamic acids 4 towards gallium(III) and indium(III) will be measured.Experimental NMR spectra were recorded on a Bruker AC 250 instrument at 250 MHz and UV spectra with a UVIKON 931 spectrometer (Kontron instruments). Compound 1. Yield: 97%, oil; dH (CDCl3) 2.26–2.28 (12 H, m, CH2CH2), 3.66 (9 H, s, CH3). Compound 2. Yield: 65%, solid, mp 175 °C; dH [2H6]DMSO) 2.16–2.17 (12 H, m, CH2CH2), 12.31 (3 H, s, COOH). Compound 3a. Yield: 77%, solid, mp 107 °C; dH ([2H6]DMSO) 1.93–2.13 (12 H, m, CH2CH2), 4.78 (6 H, s, PhCH2), 7.34–7.40 (15 H, m, C6H5), 11.09 (3 H, s, NH).Compound 3pa. Yield: 58%, oil; dH ([2H6]DMSO) 1.88–2.08 (12 H, m, CH2CH2), 7.25–7.48 (15 H, m, C6H5), 10.89 (3 H, s, NH). General Procedure for PTC N-alkylation.·To a dry mixture of 3a (9 mmol) and potassium tert-butoxide (45 mmol) was added Aliquat 336 (0.1 g). After 2 h under stirring at 50 °C, methyl iodide, n-butyl or n-octyl bromide (5–10 mol equiv.) were added and the mixture was stirred for 2 h at 50 °C. Chromatography on silica gel with a silica gel with a mixture of dichloromethane and methanol as eluent (ranging from 99:1 to 95:5) provided the desired compounds. 3b (yield: 67%), oil, dH (CDCl3 2.15–2.20 (12 H, m, ), 3.17 (9 H, s, NCH3), 4.77 (6 H, s, PhCH2), 7.36 (15 H, s, C6H5). 3c (yield: 55%), oil, dH (CDCl3) 0.87–0.93 (9 H, t, CH3), 1.25–1.35 (6 H, m, CH2), 1.54–1.63 (6 H, m, CH2), 2.08–2.27 (12 H, m, CH2CH2), 3.58–3.64 (6 H, t, NCH2), 4.75 (6 H, s, PhCH2), 7.36 (15 H, s, C6H5). 3d (yield: 48%) oil 0.87 (9 H, s, CH3), 1.25–1.30 (36 H, m, CH2), 2.08–2.23 (12 H, m, CH2CH2), 3.56–3.60 (6 H, t, NCH2), 4.75 (6 H, s, PhCH2), 7.36 (15 H, s, C6H5).General Procedure for Debenzylation.·To a solution of 3a–d (9 mmol) in methanol (50 ml) was added under argon 10% Pd–C (2.5 g) and a solution of ammonium formate (90 mmol) in methanol (100 ml). The mixture was heated at 65 °C for 12 h under argon. After cooling, the mixture was filtered through a Celite pad.The palladium was washed three times with methanol, and the filtrate was evaporated. 4a–c were chromatographed on reversed-phase TLC and 4d on silica gel. 4a (yield: 59%), solid (hygroscopic): dH ([2H6]DMSO) 1.75–2.18 (14 H, m, CH2CH2+NH2), 5.02 (3 H, br s, OH), 7.35 (3 H, s, NH). 4b (yield: 70%), oil dH ([2H6]DMSO) 2.02–2.27 (14 H, m, CH2CH2+NH2), 3.02 (9 H, s, NCH3), 7.87 (3 H, br s, OH). 4c (yield: 95%), oil: dH ([2H6]DMSO) 0.82–0.88 (9 H, t, CH3), 1.19–1.34 (6 H, m, CH2), 1.42–1.53 (6 H, m, CH2), 2.05–2.32 (14 H, m, CH2CH2+NH2), 3.43–3.48 (6 H, t, NCH2), 6.70 (3 H, br s, OH). 4d (yield: 79%), oil, dH ([2H6]DMSO) 0.85–0.87 (9 H, t, CH3), 1.26–1.33 (36 H, m, CH2), 2.10–2.30 (14 H, m, CH2CH2+NH2), 3.51–3.59 (6 H, t, NCH2), 8.43 (3 H, br s, OH). RF values on reversed-phase TLC (C18): 4a 0.75 (H2O–MeOH, 80:20); 4b 0.62 (H2O–CH3OH, 60:40); 4c: 0.17 (H2O–MeOH, 40:60). RF value on silica gel TLC: 4d: 0.20 (CH2Cl2–MeOH, 95:5). Compound 4pa. To a solution of 3pa (5.6 g, 5.34 mmol) in dichloromethane (190 ml) was added a solution of hydrochloric acid (1.1 M) in diethyl ether (30 ml).The solution was stirred for 2 h at room temperature. The precipitate was filtered off, washed with dichloromethane and dried under reduced pressure. The residue was dissolved in water, filtered and lyophilised to give 4pa (yield: 74%), solid (hygroscopic); dH ([2H6]DMSO) 1.92–2.10 (12 H, m, CH2CH2), 9.90 (3 H, br s, OH), 10.66 (3 H, s, NH). RF=0.70 [reversed-phase TLC (C18); H2O–MeOH, 80:20].Iron-exchange Reactions with EDTA.·The exchange reactions between the iron complexes and EDTA were carried out by UV spectroscopy, noting the decrease in the absorbance at 425 nm in the presence of an excess of EDTA as previously described.7 Received, 13th January 1997; Accepted, 28th February 1997 Paper E/7/00300E References 1 J. B. Neilands, Science, 1967, 156, 1443; R. J. Bergeron, Chem. Rev., 1984, 84, 587. 2 R. J. Bergeron, C. Z. Liu, J.S. McManis, M. X. B. Xia, S. E. Algee and J. Weigand, J. Med. Chem., 1994, 37, 1411. 3 C. Sappey, J. R. Boelaert, S. Legrand-Poels, C. Forceille, A. Favier and J. Piette, AIDS Res. Hum. Retroviruses, 1995, 11, 1049. 4 (a) E. V. Dehmlow, Angew. Chem., Int. Ed. Engl., 1977, 16, 493; (b) for Michael addition via PTC, see for example: V. Dryanska, K. Popandova and C. Ivanov, Synth. Commun., 1987, 17, 211; G. Bram, H. Galons, S. Labidalle, A. Loupy, M. Miocque, A. Petit, P. Pigeon and J. Sansoulet, Bull. Soc. Chim. Fr., 1989, 247; (c) for PTC N-alkylation, see for example: R. J. M. Nolte and D. J. Cram, J. Am. Chem. Soc., 1984, 106, 1416; E. V. Dehmlow and Y. R. Rao, Synth. Commun., 1988, 18, 487. 5 G. R. Newkome, C. N. Moorefield and G. R. Baker, Aldrichim. Acta, 1992, 25, 31. 6 A. M. Lobo, M. M. Marques, S. Prabhakar and H. S. Rzepa, J. Org. Chem., 1987, 52, 2925; R. J. Bergeron and J. S. McManis, Tetrahedron, 1990, 46, 5881; J. M. Altenburger, C. Mioskowski, H. d’Orchymont, D. Schirlin, C. Schalk and C. Tarnus, Tetrahedron Lett., 1992, 33, 5055; M. A. Staszak and C. W. Doecke, Tetrahedron Lett., 1994, 35, 6021; J. Zhu, S. Robin, C. Goasdou�e, A. Loupy and H. Galons, Synth. Commun., 1995, 25, 2515; S. S. Nikam, B. E. Kornberg, D. R. Johnson and A. M. Doherty, Tetrahedron Lett., 1995, 36, 197. 7 M. Akiyama, A. Katoh and T. Ogawa, J. Chem. Soc., Perkin Trans. 2, 1989, 121

ISSN:0308-2342    

DOI:10.1039/a700300e

出版商:RSC    

年代:1997

数据来源: RSC