摘要:

R4 N N R1 H O R2 R3 EtO2C NR1 NR2 O O R4 R3 1 2 3 4 5 12 3 4 5 0-MUE 1-MUE 2-MUE 3-MUE 1-PUE 3-PUE H Me Me Me Me Me HH Me Me H Me HHH Me H Me R2 R3 R4 MUE, R1 = Me PUE, R1 = Ph MH, R1 = Me PH, R1 = Ph R N O R1 H R N– O R1 R N O Me Ha R N O Me + OH– + H2O kOH kd + OH– ka Hb kb 220 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 220–221† NH-Acidities of Some Sterically Hindered Ureas† Ivan G. Pojarlieff,*a Iva B. Blagoeva,a Anthony J. Kirby,b Bozhana P. Mikhovaa and Ergun Atay‡a aInstitute of Organic Chemistry, Centre of Phytochemistry, Bulgarian Academy of Sciences, ul.Acad. G. Bonchev block 9, 1113 Sofia, Bulgaria bUniversity of Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK Introduction of an N-methyl group in to ethyl N-methylhydantoate causes a fourfold decrease in the rate of base-catalysed exchange of the N-H proton; a second methyl group restores the rate to close to that of the N-unsubstituted hydantoate; the latter effect is observed for N-phenylhydantoates.Proton exchange in amides and ureas is of continuing interest to biochemistry.1 The introduction of methyl groups into compounds 0–3, shown below, leads to unusual reactivities towards base-catalysed cyclization in the most heavily substituted esters 3: these include both a change of mechanism and the loss of the acceleration due to the gem-dimethyl effect.2 This prompted a study of the NH-acidity of these compounds as a measure of the nucleophilicity of the ureido groups in this series of ureidoesters.Rates of base-catalysed hydrogen exchange were measured by means of dynamic NMR. The collapse of the methyl doublet due to the NH–CH3 coupling in the w-methyl hydantoates and the broadening of the NH peak of the w-phenyl esters with changing pH were monitored in buffers. These exchange phenomena are due to the processes shown in Scheme 1. Pseudo-first-order rates of hydrogen exchange, kexch, were obtained as described in the Experimental section.In the pH region where exchange phenomena could be observed, spectra had to be recorded rapidly as cyclization to hydantoin is a competing reaction. To calculate the second-order rates, kOH=kexch/aOH, aOH was taken as antilog (pH µ14), where pH is the glass-electrode value measured in the buffer containing the correct amount of acetonitrile. The acidity constant was obtained as KNH= kOH kd Kw with kd, the diffusion-controlled rate for the protonation of the ureide anion, being taken as 1010 dm3 sµ1 molµ1 and Kw, the ionic product of water, as 10µ14.Because of poor solubility, spectra had to be run in 5:1 (v/v) water–acetonitrile. In this solvent mixture pKw is little different from that of pure water [14.33 in 20% (w/w) MeCN at 25 °C]3 and, in view of the remaining uncertainties, refinements were considered unwarranted. 3-PUE is still less soluble and 50% aqueous MeCN was used. In this medium pKw differs considerably3 from 14 and the respective pK values were calculated as above only for the sake of comparison.As far as the ring-closure reaction is concerned, the results in Table 1 show that differences in reactivity between compounds 1 and 3, in both the MUE and PUE series, cannot be attributed to the different basicity of the ureide anions. 2-MUE, with one methyl group at the 2 position, is considerably less acidic than 1-MUE, with no methyl group. This is not likely to be simply an inductive effect; in a Z-conformation on the ester side of the urea molecule, an extra methyl group can be expected to hinder the solvation of the negatively charged oxygen in the anion.The reversal of this trend in compounds 3 is most likely due to a steric effect: strain relieved by twisting the dialkylamino group out-of-plane diminishing amide conjugation. This should make the NH proton more acidic because of increased conjugation within the secondary amide group. Strong acidifying effects upon N-methyl substitution of secondary acylureas have been observed.4 The less heavily substituted ethyl hydantoates have been prepared by Kav�alek and S8t�erba.5 Esters 2 and 3, however, cyclized rapidly in the presence of moisture and had to be prepared under strictly anhydrous conditions, as described in the Experimental section.Experimental Melting points are uncorrected. 1H NMR spectra were recorded on a Bruker WM-250 instrument. pH Values were measured with a Radiometer pH M 84 Research pH-meter using a GK 2401 C electrode.Materials.·Inorganic reagents and buffer components were of analytical-reagent grade and used without further purification. Buffer solutions were prepared with CO2-free water, to 0.03 M total *To receive any correspondence (e-mail: ipojarli@gate.orgchm. acad.bg). †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). ‡Formerly Denis T. Tashev of ref. 2. Scheme 1 Table 1 Rates of base-catalysed hydrogen exchange in ethyl hydantoates and pKNH estimates in 5:1 (v/v) water–acetonitrile at 19 °C Compound pH kexch/sµ1 kOH/dm3 sµ1 molµ1 pK In 5:1 (v/v) water–acetonitrile 0-MUEa 1-MUE 2-MUE 3-MUE 1-PUE 9.84 9.43 9.84 10.21 10.45 9.43 6.90 7.19 12 4.0 11.5 5.5 11 2.5 6.3 12.2 1.7Å105 1.6Å105 3.6Å104 9.3Å104 7.9Å107 18.8 18.8 19.45 19.0 16.1 In 1:1 (v/v) water–acetonitrile 1-PUE 3-PUE 7.44 7.44 4.5 5.8 1.6Å107 2.1Å107 16.8 16.7 aFor 3-NH we obtained kOH=1.3Å106 dm3 sµ1 molµ1, pK=17.9.J.CHEM. RESEARCH (S), 1997 221 concentration, and the ionic strength was adjusted with KCl to 0.1 M. CD3CN was 99% from Aldrich. Ethyl Hydantoates.·General procedure. A slight excess (8%) of methyl or phenyl isocyanate was added to the freshly distilled amino ester (5 mmol) in dry benzene (5 ml) under ice cooling. The mixture was stirred for 15 min at 0 °C and then for 1 h at room temperature.Where the products precipitated they were filtered off and washed with dry benzene and hexane, otherwise the reaction mixture was evaporated to dryness and the solids recrystallized from dry benzene. The yields of pure esters were 86–96%. Compounds 0-MUE, 1-MUE and 1-PUE were prepared by the above procedure and were identified by comparison with the mps and NMR parameters described in ref. 4. Ethyl 2,3-dimethyl-5-phenylhydantoate (2-PUE) had mp 95–96.5 °C; dH (CDCl3) 1.27 (t, 3 H, MeCH2OCO), 1.45 (d, 3 H, MeCH), 2.98 (s, 3 H, MeN), 4.19 (q, 2 H, CH2OCO), 5.09 (q, 1 H, CHNMe), 6.54 (s, 1 H, HNPh), 7.03–7.38 (m, 5 H, Ph) (Found: C, 62.51; H, 7.48; N, 11.14.C13H18N2O3 requires C, 62.38; H, 7.25; N, 11.19%). Ethyl 2,2,3-trimethyl-5-phenylhydantoate (3-PUE) had mp 108.5–110 °C; dH (CDCl3) 1.23 (t, 3 H, MeCH2OCO), 1.43 (s, 6 H, Me2CH), 3.00 (s, 3 H, CH3N), 4.18 (q, 2 H, CH2OCO), 6.33 (s, 1 H, HNPh), 7.01–7.36 (m, 5 H, Ph) (Found: C, 63.55; H, 7.51; N, 10.87.C14H20N2O3 requires C, 63.61; H, 7.62; N, 10.60%). Hydantoates 2-MUE and 3-MUE were obtained in situ as described below. Dynamic NMR.·The ready cyclization of the ureido esters limited the time and the pH region (below 7 for PUE and below 10.5 for MUE) available for recording the spectra. Table 2 lists the NMR parameters for the esters and the product hydantoins. The final solutions were prepared by mixing 0.4 ml of the aqueous buffer (formate, acetate, phosphate, borate or carbonate) with 0.1 ml of an ester CD3CN solution (0.1 g in 1 ml).Esters 2-MUE and 3-MUE were prepared in situ by mixing equal amounts of 10µ3 M solutions of the respective amino ester and of methyl isocyanate in CD3CN just before recording the spectra. In the case of MUE, spectra for the 5-Me doublet could be taken before and after coalescence in solutions of various pH. The relaxation time, T2, in each spectrum was determined from the band width at half intensity of the 3-methyl signal.For 0-MUE one of the lines of the ethoxymethyl group was used, adding the difference of this line and a line of the 5-Me signal at slow exchange. Estimate kexch=k=ka+kb were obtained by means of approximate solutions; 6 line-intensity methods for cases with slow7 and fast8 exchange were preferred. The values for the rate constants were then refined by means of complete line-shape-analysis simulations. 9 In the case of PUE, line-broadening of the NH signal was monitored: kexch=p(W*µW0), where W* is the line-width of the exchange-broadened signal and W0 the width in the absence of observable exchange.Following the recommendations of Perrin et al.,10 instrument inhomogeneity was compensated for by subtracting the width of a line of the ester methyl triplet from every NH line width. We thank the National Foundation for Scientific Research of Bulgaria for funding this research and the Bulgarian Academy of Sciences and The Royal Society for travel funds.We thank also Dr N. Vassilev for help with the CLSA program. Received, 24th December 1996; Accepted, 28th February 1997 Paper E/6/08619E References 1 C. L. Perrin, Acc. Chem. Res., 1989, 22, 268. 2 I. B. Blagoeva, D. T. Tashev and A. J. Kirby, J. Chem. Soc., Perkin Trans. 1, 1989, 1157; I. B. Blagoeva, D. T. Tashev and A. J. Kirby, unpublished results. 3 U. Mandal, S. Bhattacharya and K.K. Kundu, Indian J. Chem., 1985, 24A, 191. 4 J. Kav�alek, J. Jirman, V. Mach�acek and V. S8t�erba, Collect. Czech. Chem. Commun., 1987, 52, 1992 and references cited therein. 5 J. Kav�alek and V. S8t�erba, Collect. Czech. Chem. Commun., 1986, 51, 375. 6 V. S. Dimitrov in Recent Developments in Molecular Spectroscopy, ed. B. Jordanov, M. Kirkov and P. Simova, World Scientific, Singapore, 1988, p. 476. 7 R. K�uspert, J. Magn. Reson., 1982, 47, 91. 8 V. D. Dimitrov, Org. Magn. Reson., 1974, 6, 16. 9 D. S. Stephenson and D. Binsch, J. Magn. Reson., 1978, 32, 145; QCPE, 1978, 11, 365. 10 C. L. Perrin, E. R. Johnson, C. P. Lollo and P. A. Kobrin, J. Am. Chem. Soc., 1981, 103, 4691. Table 2 1H NMR spectra of ureido esters and hydantoins in 5:1 (v/v) water–acetonitrile [HD2CCN (d 1.94) as reference, splittings in Hz in parentheses] Compounds 1-Me 2-H 2-Me 3-Me 5-H 5-Me OCH2Me OCH2Me MUE and PUEa 0-MUE 1-MUE 2-MUE 3-MUE 1-PUE 3-PUEc,d 3.780d (6.1) 3.955s 4.073q (7.1) 4.032s 1.266d (7.1) 1.261s 1.327s 2.805s 2.691s 2.706s 2.967s 2.913 2.553d (4.6) 2.595d (4.5) 2.596d (4.4) 2.550d (4.5) 4.092q (7.2) 4.095q (7.2) 4.073q (7.1) 4.034q (7.2) 4.111q (7.2) 1.149t (7.2) 1.152t (7.2) 1.141t (7.2) 1.133t (7.1) 1.156t (7.2) 1.122 (7.2) MH and PHa 0-MH 1-MH 2-MH 3-MH 1-PHe 3-PHc 2.836s 2.738s 2.757s 2.929s 2.862s 2.834 2.836s 2.811s 2.853s 3.917s 3.910s 3.973q (7.0) 4.100s 1.278d (7.0) 1.257s 1.408s aSee formulae for numbering in esters and hydantoins. bd 5-Ph: o-H 7.185, m-H 7.266, p-H 7.064; NH 8.03. cIn 50% H2O–CD3CN v/v. dd(NH) 7.98. ed (3-Ph) 7.25m (3 H),

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DOI:10.1039/a608619e

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年代:1997

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222 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 222–223† Acid–Base Equilibria of Cysteine in Artificial Sea Water: Effect of Ionic Strength on the Basis of Specific Interaction Theory† Teresa Vilari�no, Sarah Fiol, Isabel Brandariz, Roberto Herrero and Manuel E. Sastre de Vicente* Dpto de Qu�ýmica Fundamental e Industrial, Facultad de Ciencias, Universidad de La Coru�na, 15071-La Coru�na, Spain Artificial sea water, containing NaCl, KCl, CaCl2, MgCl2 and Na2SO4, was used as a standard medium in potentiometric equilibrium studies of the sulfur-containing amino acid cysteine: the dependence of activity coefficients on ionic strength, and thus salinities, is discussed according to different models based on the Specific Interaction Theory.Taking into account the relevance of protonation in biologically significant cysteine-rich ligands that take part in major metal-complexation processes, we thought it of interest to investigate the effect of ionic strength on the acid–base equilibria of cysteine in artificial sea water (ASW), reported as a good approximation in marine chemistry studies regarding the real situation (natural sea water).1,2 Although the ionization equilibria of cysteine have been studied by several authors, all studies in this context have been carried out at a fixed ionic strength, as noted in a recent review.3 Lately, our group has started a systematic study of this amino acid and some results obtained in a simple electrolytic medium (KNO3) have been already reported.4 The acid– base equilibria can be represented by A2µ+H+mAHµ (1) AHµ+H+mAH2 (2) AH2+H+mAH3 + (3) As is shown, the fully protonated form of cysteine contains three dissociable protons (CO2H, NH3 +, SH).Clearly, the most acidic of these lies on the carboxylic group. By contrast, assigning the donating groups involved in its two most basic equilibria is less straightforward, since it is generally accepted that proton ionization occurs simultaneously from the SH and NH3 + groups and the related constants result from intermingled microscopic processes.3,5,6 Experimental The L-cysteine used was supplied by Merck (for biochemistry, a99%).The potentiometric apparatus, procedure and conditions used have been described elsewhere.7–9 The synthetic sea water samples were prepared from NaCl, KCl, CaCl2, MgCl2 and Na2SO4 as electrolytes following the seawater recipe of Millero.9,10 The salinity, S, is related to the real ionic strength by the equation11 I= 19.9273S 1000µ1.00511S (4) In Table 1 the stoichiometric equilibrium constants (molality scale) are compiled.No pK1* values were considered owing to the relatively high errors involved, consistent with previous findings of other authors.4 Results and Discussion Even though a great number of interactions might be involved in such a complex medium as seawater, and taking into account the moderate values of the ionic strength in the working range studied, we considered the interactions of cysteine in artificial seawater to be given by a simple equation.Fig. 1 shows the variation of pK2* and pK3* with the ionic strength as established from various models (Table 2) based on specific interaction theories (SIT).12 The models result from empirical modifications of the Debye–H�uckel equation by inclusion of different terms consisting of powers of the ionic strength. We tried different values for the parameter appearing in the Debye–H�uckel term. Guggenheim and Turgeon13 proposed taking c=1 for all solutes and letting the specific properties of each solute appear in the linear term, whilst later Scatchard14 showed that a value aJ=1.5 led to better results at ionic strength greater than 0.1 M.As shown in Fig. 1, all the proposed equations fit the log K2*µI and log K3*µI plots for cysteine within experimental error and lead to extrapolated values (log KT) at 25 °C that are consistent with those recently recommended by IUPAC3 (see Table 3).On the other hand, the plots exhibit a flat minimum over the ionic strength range 0.20–0.72 mol kgµ1. The presence of a minimum is typical of equilibria of the type AHmAµ+H+ or similar, where a separation of electric charge occurs,15 but not, for example, for an isocoulombic equilibrium of the type BH+mB+H+. The most simple way of accounting for the appearance of the minimum is provided by the Guggenheim equation,13 a model already proposed empirically by Br�onsted in previous studies,16 which includes the electrostatic long-range term and a linear term proportional to the ionic strength whose coefficient is generally ascribed to the presence of specific interactions; competition between the two types of terms (specific and non-specific interactions) determines the position and amplitude of the minimum for equilibrium (3) above.In fact, a similar observation, viz.a virtually negligible effect of the ionic strength (a quasi-flat minimum) between 20 mM and 1 M on various derivatives of cysteine led Snyder17 to propose the following relation in studying the use of Br�onsted equations for predicting inductive effects on rate constants for the thiol–disulfide exchange: log K*=log KT+ bJI 1+cJI (5) The value of log K* at infinite ionic strength would lead to a pKl value (log Kl=log KT+b/c) influenced by inductive *To receive any correspondence (e-mail: eman@udc.es).†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 Stoichiometric equilibrium constants of cysteine in ASW at 25 °C, molal scale, standard deviations in parentheses S (%) I/mol kgµ1 µlog (K2/mol kgµ1) µlog (K3/mol kgµ1) 0.50 1.05 1.45 2.00 2.50 2.90 3.50 0.10 0.21 0.29 0.40 0.51 0.60 0.72 8.149 (0.001) 8.080 (0.004) 8.073 (0.04) 8.045 (0.009) 8.042 (0.003) 8.086 (0.02) 8.07 (0.02) 10.168 (0.005) 9.945 (0.03) 9.876 (0.03) 9.844 (0.02) 9.842 (0.03) 9.831 (0.06) 9.80 (0.005)J.CHEM. RESEARCH (S), 1997 223 effects but not by purely electrostatic effects; this is equivalent to resolving pK into an electrostatic term, represented by the contribution b/(1+cJI) and other, non-electrostatic terms affected by the inductive effect. However, the assumption that electrostatic effects are represented exclusively by the electrostatic contribution up to Ihl should only be taken as an approximation.Although extrapolating to infinite ionic strength from eqn. (5) might seem too speculative, since Snyder used it just in the range 20 mMRIR1 M, it should be noted that this equation leads to a finite value of pKl and that any other equations such as those shown in Fig. 1 will lead to an infinite value of this parameter at Ihl. Whether or not an acid–base equilibrium constant (or its inverse logarithm) is finite when the solution ionic strength tends to infinity probably remains uncertain. The answer to this equation relies on the way different chemical-equilibrium models for a concentrated electrolyte solution are used.M. S. V. thanks the Xunta de Galicia for financial support received through Project XUGA 10304B94. Received, 3rd March 1997; Accepted, 12th March 1997 Paper E/7/01454F References 1 F. M. M. Morel and J. G. Hering, Principles and Applications of Aquatic Chemistry, Wiley–Interscience, New York, 1993, ch. 6. 2 C. De Stefano, C. Foti, S. Sammartano, A. Giunguzza and C. Rigano, Ann. Chim. (Rome), 1994, 84, 159. 3 G. Berthon, Pure Appl. Chem., 1995, 67, 1117. 4 T. Vilari�no, S. Fiol, I. Brandariz, X. L. Armesto and M. E. Sastre de Vicente, J. Chem. Soc., Faraday Trans., 1997, 93, 413. 5 R. Benesh and R. Benesh, J. Am. Chem. Soc., 1955, 77, 5877. 6 A. Walters and D. E. Leyden, J. Electroanal. Chem., 1982, 132, 357. 7 R.Herrero, X. L. Armesto, F. Arce and M. Sastre de Vicente, J. Solution Chem., 1992, 21, 1185. 8 R. Herrero, I. Brandariz and M. Sastre de Vicente, Ber. Bunsenges. Phys. Chem., 1993, 97, 59. 9 S. Fiol, I. Brandariz and M. Sastre de Vicente, Mar. Chem., 1995, 49, 215. 10 F. J. Millero, Limnol. 1, 839. 11 S. L. Clegg and M. Whitfield, in Activity Coefficients in Electrolyte Solution, ed. K. S. Pitzer, CRC Press, Boca Raton, 2nd edn., 1991, ch. 6. 12 K. S. Pitzer, in Activity Coefficients in Electrolyte Solution, ed. K. S. Pitzer, CRC Press, Boca Raton, 2nd edn., 1991, ch. 3. 13 E. A. Guggenheim and J. C. Turgeon, Trans. Faraday Soc., 1955, 51, 747. 14 G. Scatchard, J. Am. Chem. Soc., 1961, 83, 2636. 15 C. W. Davies, Ion Association, Butterworths, London, 1962, ch. 3. 16 (a) J. N. Br�onsted, J. Am. Chem. Soc., 1922, 44, 877; (b) J. N. Br�onsted, J. Am. Chem. Soc., 1922, 44, 938. 17 G. H. Snyder, J. Biol. Chem., 1984, 259, 7468. Fig. 1 Fitting curves based on specific interaction models appearing in Table 2: ———, Pitzer; µµµ, Scatchard; ······, Guggenheim Table 2 Dependence of stoichiometric equilibrium constants on ionic strength according to different specific interaction models log Ki*=log KTi + Guggenheim model Scatchard model Pitzer modela Debye–H�uckel termb z 2 ln 10 µ0.509JI 1+cJI z 2 ln 10 µ0.509JI 1+aJJI z 2 ln 10 f (g) + + + Linear term ei I Pi I Ai I + + Polynomic terms Qi I2+. . . Bi I2 + Exponential terms Ci[1µ(1+2JI)eµ2JI]+f(med) aRefs. 12 and 9; f(g)\µ0.392 C JI 1+1.2JI + 2 1.2 ln (1+1.2JI)D; f(med\ASW)\0.2882[µ1+(1+2JI+2I)eµ2JI]. bz\iµ1. Table 3 Thermodynamic equilibrium constants obtained by applying specific interaction models appearing in Table 2 Fitting model µlog K2 T µlog K3 T Guggenheim c\1.5 c\1.2 c\1.0 8.33�0.02 8.34�0.01 8.35�0.01 10.53�0.04 10.55�0.04 10.57�0.03 Scatchard c\1.5 c\1.2 c\1.0 8.37�0.03 8.37�0.03 8.38�0.03 10.63�0.06 10.64�0.05 10.65�0.05 Pitzera 8.39�0.04 10.71�0.07 Berthon reviewb 8.36�0.03 10.75�0.05 aQuadratic t

ISSN:0308-2342    

DOI:10.1039/a701454f

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年代:1997

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N NH O OH N NH O O NH O CONH2 O 1 2 3 NH2 O NH2 NH2 O NH O OAc N NH O OH 4 i ii 1 224 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 224† Comments on the Asymmetric Synthesis of Chrysogine† Jan Bergman* Institute of Biosciences at Novum, Department of Organic Chemistry, S-141 57 Huddinge, Sweden and Department of Organic Chemistry, Royal Institute of Technology, S-100 44 Stockholm, Sweden The absolute configuration of the mould metabolite chrysogine, (S)-(µ)-2-(1-hydroxyethyl)quinazolin-4(3H)-one, was first determined by asymmetric synthesis in 1990 and not in 1996 as recently claimed.The mould metabolite chrysogine 1 was isolated in 1973 by Hikino et al. from strains of Penicillium chrysogenum1 and later by Chadwick from Alternaria citri.2 Related secondary metabolites such as 2-acetylquinazolin-4(3H)-one 2 and 2-pyruvoylaminobenzamide 3 have also been isolated, the former from Fusarium culmorum3 and Alternaria citri2 and the latter from Penicillium chrysogenum4 and Colletotrichum lagenarium.5 In 1990 we established, in connection with a comprehensive study,6 the absolute configuration of chrysogine as (S)-(µ)-2-(1-hydroxyethyl)quinazolin-4(3H)-one by asymmetric synthesis as outlined in Scheme 1.The sequence is conveniently completed in one pot but the intermediate 4 can be isolated in 76% yield. Ring closure of 4 and subsequent saponification by aqueous sodium carbonate at room temperature gives chrysogine 1 (75%) with an optical rotation of [a]D µ41°.This optical rotation is higher than that ([a]D µ26�4°) reported by Hikino et al.1 In 1992 Tamm and co-workers,7 unaware of our6 previous work, incorrectly stated ‘The configuration of the chiral centre of 1 has never been determined’.7 The Swiss workers correctly arrived at the conclusion that chrysogine has the S configuration using NMR methods. In 1993 Tsantrizos et al. isolated the R form of chrysogine (less than 20% ee) from Fusarium laterritium Nees. The absolute configuration was proposed from studies using the Mosher ester method.8 The Canadian workers were likewise unaware of previous studies, as in fact the pure antipode of (S)-chrysogine had already been prepared from 2-aminobenzamide and (S)-2-chloropropanoyl chloride or, in a better ee, by inversion of the S form by the Mitsunobu reaction.6 The unawareness of the relevant literature already touched upon has recently led to a paper9 which claims to report the first asymmetric synthesis of chrysogine.The method is identical with ours described in 1990, with the exception that the Indian workers used sodium hydroxide rather than sodium carbonate in the final cyclization step. This change is probably not the major cause for the relative low rotation ([a]Dµ27°) reported, rather we consider it likely that the (S)-2-acetoxypropanoyl chloride used by the Indian workers was partially racemic. Anyhow, it is interesting to note that both forms of chrysogine isolated from Nature are partially racemic. Finally, Hikino et al.coined the name chrysogine which has been used by all subsequent workers as well as in a recent review on quinazoline alkaloids.10 The name ‘chrysogenine’ was probably used by the Indian workers inadvertently. Received, 12th February 1997; Accepted, 21st February 1997 Paper E/7/01012E References 1 H. Hikino, S. Nabetani and T. Takemoto, Yakugaku Zasshi, 1973, 93, 619. 2 D.J. Chadwick and I. W. Easton, Acta Crystallogr., Sect. C, 1983, 39, 454. 3 M. M. Blight and J. F. Grove, J. Chem. Soc., Perkin. Trans. 1, 1974, 1691. 4 P. J. Suter and W. B. Turner, J. Chem. Soc. C, 1967, 2240. 5 Y. Kimura, T. Inoue and S. Tamura, Agric. Biol. Chem., 1973, 37, 2213. 6 J. Bergman and A. Brynolf, Tetrahedron, 1990, 46, 1295. 7 D. Niederer, C. Tamm and W. Z�urcher, Tetrahedron Lett., 1992, 33, 3997. 8 Y. S. Tsantrizos, Xiao-Jin Xu, F. Sauriol and R. C. Hayes, Can. J. Chem., 1993, 71, 1362. 9 D. K. Maiti, P. P. Ghoshdastidar and P. K. Bhattacharya, J. Chem. Res. (S), 1996, 306. 10 S. Johne, in Rodd’s Chemistry of Carbon Compounds, vol. IV/J, ed. M. F. Ansell, Elsevier, Amsterdam, 2nd edn., 1995, Supplements, pp. 223–240. *E-mail: jabe@cnt.ki.se. †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: i, (S)-2-acetoxypropanoyl chloride; ii, Na2CO3

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DOI:10.1039/a701012e

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年代:1997

数据来源: RSC

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Enantiospecific Synthesis of Analogues of the Diketide Intermediate of the Erythromycin Polyketide Synthase (PKS) Rebecca C. Harris, Annabel L. Cutter, Kira J. Weissman, Ulf Hanefeld, Ma�Ê ire C. Timoney and James Staunton* Department of Chemistry, University of Cambridge, LensAeld Road, Cambridge CB2 1EW, UK The four stereoisomers of 3-hydroxy-2-methylpentanoic acid (1a�}d) and the structurally modified acids 1e�}j have been synthesised enantiospecifically and converted into p-nitrophenyl ester and thioester derivatives; as the activated derivatives; they are available for investigations into the substrate selectivity of polyketide synthase (PKS) domains.In recent years, the substrate speciRcity of modular poly- ketide synthases, the enzymes responsible for a range of clinically important antibiotics, have been probed through feeding studies with analogues of biosynthetic inter- mediates.1 In our studies of the 6-deoxyerythronolide B synthase (DEBS), the erythromycin-producing PKS, we desired a range of diketide analogues.We synthesised all four stereoisomers of 3-hydroxy-2-methylpentanoic acid 1a�}d, as well as analogues with the stereochemistry of 1a which incorporated further structural modiRcations, 1e�}j (Fig. 1). All diketides (1a�}j) were converted into activated p-nitrophenyl esters and/or N-acetylcysteamine thioesters.2 The synthetic strategy used in all cases centred on Evans aldol methodology.3�}6 The appropriate chiral auxiliary was acylated, C-2, C-3 stereochemistry established through a boron-mediated aldol reaction, and then the resulting acid was cleaved from the auxiliary using lithium hydroperoxide (Scheme 1).We chose to derivatise the acids as their N-acetylcysteamine (NAC) thioesters and p-nitrophenyl esters; the NAC moiety is a good structural mimic for the 4'-phosphopantetheine group of PKS acyl carrier proteins,7 while nitrophenyl esters, though less accurate structural analogues, are well-known serine protease substrates whose reactions can be monitored by UV�}VIS spectroscopy.8 Synthesis of the derivatives was achieved by coupling the acids with N-acetylcysteamine or p-nitrophenol in the presence of 1,3-dicyclohexylcarbodiimide (DCC) and 4- dimethylaminopyridine (DMAP);9 excess NAC was removed by �Pash column chromatography with CuSO4-impregnated silica gel (Scheme 1).7 The derivatives 4e�}i, incorporating the same stereo- chemistry as 1a but with a range of functionalities, were accessed by the same route as for 1a (Scheme 1); functional variation was introduced through the choices of acid chlor- ide in the acylating step and aldehyde in the aldol reaction.Compound 4j was generated directly from 3j, by reacting it with N-acetylcysteamine in the presence of lithium bis- (trimethylsilylamide).7 Techniques used: 1H and 13C NMR, column chromatography, mass spectra, polarimetry References and notes: 10 Schemes: 4 Received, 21st January 1998; Accepted, 13th February 1998 Paper E/8/00584B References cited in this synopsis 1 R.Pieper, C. Kao, C. Khosla, G. Luo and D. E. Cane, Chem. Soc. Rev., 1996, 25, 297; J. Staunton, P. Ca€rey, J. F. Aparicio, G. A. Roberts, S. S. Bethell and P. F. Leadlay, Nat. Struct. Biol., 1996, 3, 188. 2 K. J. Weissman, C. J. Smith, R. Aggarwal, U. Hanefeld, J. Staunton and P. F. Leadlay, Angew. Chem., Int. Ed. Engl., in the press. 3 J. R. Gage and D. A. Evans, Org. Synth., 1990, 68, 83. 4 D. E. Cane, P. C. Prabhakaran, W. Tan and W. R. Ott, Tetrahedron Lett., 1991, 32, 5457. 5 M. A. Walker and C. H. Heathcock, J. Org. Chem., 1991, 56, 5747. 6 B. C. Raimundo and C. H. Heathcock, Synlett, 1995, 12, 1213. 7 I. H. Gilbert, M. Ginty, J. A. O'Neill, T. J. Simpson, J. Staunton and C. L. Willis, Bioorg. Med. Chem. Lett., 1995, 5, 1587. 8 R. Aggarwal, P. Ca€rey, P. F. Leadlay, C. J. Smith and J. Staunton, J. Chem. Soc., Chem. Commun., 1995, 1519. 9 B. Neises and W. Steglich, Angew. Chem., Int. Ed. Engl., 1978, 17, 522. J. Chem. Research (S), 1998, 283 J. Chem. Research (M), 1998, 1230�}1247 Fig. 1 Structures of diketide acids Scheme 1 *To receive any correspondence. J. CHEM.

ISSN:0308-2342    

DOI:10.1039/a800584b

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Syntheses and Spectral Properties of New Dicyanopyrazine-related Heterocycles from Diaminomaleonitrile Jae-yun Jaung,a Masaru Matsuokab and Koushi Fukunishi*a aDepartment of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606, Japan bLaboratory of Material Science, Kyoto Women's University, Imakumano, Higashiyama-ku, Kyoto 605, Japan A series of new dicyanopyrazine-related heterocycles are synthesized and their spectral properties correlated with their structures. 2,3-Dicyanopyrazine derivatives derived from diaminoma- leonitrile and 1,2-dicarbonyl compounds have been applied to synthesize a wide variety of heterocycles useful as bio- active substances and as coloring materials. We are inter- ested in the substituent e€ects of pyrazine chromophores on their chemical, electronic and physical properties.4,5 Pyrazine chromophores have large dipole moments and a strong �Puorescence even in the solid state and are of interest with respect to functional dye materials.We report the correlation of their structures with their functionalities from the points of view of their intermolecular interactions. We report the syntheses of new dicyanopyrazine-related heterocycles including pyrazinoporphyrazines. Their absorp- tion and �Puorescence properties were correlated with their chemical structures. 2,3-Dicyanoquinoxalines 8 were conventionally prepared by the Wittig reaction of 2,3-bis(bromomethyl)-5,6-dicyano- pyrazine 3 with 1,2-dicarbonyl compounds.The 2,3-dicyanopyrrolo[2,3-b]pyrazines 13 and their furo analogues 15 were synthesized by the cyclization of 2,3- dichloro-5,6-dicyanopyrazine 10 with carbonyl compounds and enamines, respectively. Compound 14, the N-aryl ana- logue of 13 could be prepared alternatively by the cycliza- tion of 2-arylamino-3-chloro-5,6-dicyanopyrazine with the appropriate diarylketone in the presence of sodium hydride. Pyrazinoporphyrazines 16 and 17 were easily synthesized from the corresponding dicyanopyrazine derivatives 8 and 13, respectively.Dye 16 is insoluble in almost all organic solvents and absorbs at 840 nm in concentrated sulfuric acid. On the contrary, dye 17, having long alkyl substitu- ents, is readily soluble in cyclohexane and chloroform. They absorb at around 712 nm and �Puoresce at 719 nm. A very small Stokes' shift of 7 nm was observed. It is very useful that dye 17 showed a red �Puorescence even in the solid state which makes it suitable as an emitter for an electrolumines- cence device.Dye 17 showed a crystal morphology a€ected by intermolecular hydrophobic interactions of the alkyl sub- J. Chem. Research (S), 1998, 284�}285 J. Chem. Research (M), 1998, 1301�}1323 Scheme 1 Scheme 2 Fig. 3 Temperature dependence of the absorption spectra of 17a in cyclohexane *To receive any correspondence. 284 J. CHEM. RESEARCH (S), 1998stituents. They showed reversible spectral changes depending on the polarity of solvent and temperature (Fig. 3). Techniques used: 1H NMR spectroscopy, mass spectrometry, UV�}VIS, �Puorescence spectrophotometry, elemental analysis Table 1: Reaction of 6 with 1,2-dicarbonyl compounds Table 2: Syntheses of pyrrolopyrazines and furopyrazines Table 3: Syntheses of quinoxalinoporphyrazines and pyrrolopyra- zinoporphyrazines Table 4: Visible and �Puorescence spectra of 7 and 2,3-dicyano- quinoxalines 8 Table 5: Visible and �Puorescence spectra of 13, 14 and 15 Table 6: Visible and �Puorescence spectra of 16 and 17 Schemes: 7 References: 12 Fig. 1: The e€ects of solvent polarity on the absorption spectra of 17a Fig. 2: Spectral changes of 17a in cyclohexane by the addition of chloroform Received, 10th November 1997; Accepted, 18th February 1998 Paper E/7/08049B References cited in this synopsis 4 J. Y. Jauang, M. Matsuoka and K. Fukunishi, Dyes Pigments, 1996, 31, 141. 5 J. Y. Jaung, M. Matusoka and K. Fukunishi, J. Heterocycl. Chem., 1997, 34, 653. J. CHEM.

ISSN:0308-2342    

DOI:10.1039/a708049b

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Kinetic Study of Ruthenium(III)-catalysed Oxidation of 2-Methylpentane-2,4-diol by Alkaline Hexacyanoferrate(III) Antonio E. Mucientes,* Francisco J. Poblete, Rafael E. Gabaldon, Maria A. Rodriguez and Francisca Santiago Departamento de Qu©¥¡� mica F©¥¡� sica, Facultad de Qu©¥¡� mica, Universidad de Castilla-La Mancha, Campus Universitario s/n, 13071 Ciudad Real, Spain A concerted hydrogen-atom transfer one-electron transfer mechanism is proposed for the ruthenium(III)-catalysed oxidation of 2-methylpentane-2,4-diol by alkaline hexacyanoferrate(III). Some substrates like alcohols, organic acids etc., which are not easily oxidized by common oxidants, can be oxidized in the presence of transition metal ions.Owing to the fact that these methods are expensive, the use of transition metals in catalytic quantities in combination with an inexpensive cooxidant is an attractive alternative.1,2 Here, we describe the ¢çrst reported study for the ruthenium(III)-catalysed oxidation of 2-methylpentane-2,4- diol by alkaline hexacyanoferrate(III).Experimental All the reagents used were of A.R. grade, except for the catalyst which was 100% in RuIII. The aqueous solutions handled were prepared in water obtained by a Millipore-Milli Q Water Puri¢çcation System. The ionic strength was kept constant at 0.5 M by adding sodium perchlorate. The progress of the reaction was followed spectrophotometrically by measuring the optical absor- bance of hexacyanoferrate(III) at 420 nm on a Perkin Elmer Lambda 3B spectrophotometer equipped with a thermostated cell holder which kept the temperature constant at 30.020.1 8C.The initial rates method17 was used for kinetic analysis. The initial rates were obtained by ¢çtting the absorbance versus time data, for a small percentage of the reaction (5% or less)17 to a straight line, A a a0aa1t, by the least-squares method; the slope provides the initial rate, v0=a1=¢§ (dA/dt)0, given in absorbance units. The initial rate, v0, expressed in M min¢§1 is given by v0=¢§1/e(dA/dt)0= ¢§ (d[Fe(CN)6 3¢§]/dt)0, where e a 1000 M¢§1 cm¢§1 at 420 nm.Under kinetic conditions 4-hydroxy-4-methylpentan-2-one was the only reaction product found by gas chromatography. Moreover, under the conditions [Fe(CN)6 3¢§]w[diol], the reaction was allowed to go to completion and the residual oxidant concentration was deter- mined spectrophotometrically. These measurements indicated that 1 mole of alcohol reacted with 2 moles of oxidant.Results Fig. 1 shows that the initial rate, v0, varies linearly with the hexacyanoferrate(III) concentration at low concen- trations (¢çrst-order kinetics) and becomes independent of hexacyanoferrate(III) concentration (zero-order kinetics) at high concentrations. It has been observed that at low concentration of 2-methylpentane-2,4-diol the initial rate is proportional to [diol] (¢çrst-order kinetics); at a higher concentration of 2-methylpentane-2,4-diol the initial rate becomes indepen- dent of that concentration (zero-order kinetics).It has been observed that on increasing [OH¢§] the initial rate increases and then decreases showing a maximum value. The variation of the experimental initial rate with the medium basicity is complicated and obeys eqn. (5). v0 a A1aOH¢§a a A2aOH¢§a2 1 a B1aOH¢§a a B2aOH¢§a2 O5U This equation was ¢çtted by a non-linear regression method. The average error was found to be 4.5%.The plots of v0 versus catalyst concentration gave straight lines with zero intercept. Hence, the kinetics are ¢çrst order in catalyst concentration and the rate of the uncatalysed reaction is negligible in comparison with the catalysed reaction. The hydrogen on the a-carbon of the alcohol is necessary for the reaction to occur,19 since tertiary alcohol (2,3-dimethylbutane-2,3-diol) was unreactive under kinetic conditions. When acrylonitrile22 (0.01 M) was added to the reaction mixture in a typical kinetic experiment, the reaction rate decreased (15%), while no di€erence in the reaction rate was observed when acetonitrile (0.01 M) was added.More- over when, in a typical kinetic experiment, 2,4,6-triert-butyl- phenol23 (1.610¢§4 M) was added to the reaction mixture the reaction rate decreased (40%). These facts indicate the generation of free radicals in the reaction. The oxidation of cyclobutanol24 under kinetic conditions yields butyraldehyde as the main product. Discussion Optical behaviour of an aqueous solution 4.010¢§5 M RuCl3 in the [OH¢§] a 10¢§3¡¾0.4 M range may involve the existence of several hydroxo-aquo ruthenium complexes in the equilibrium as follows: RuOH2OU6 3a a OH¢§ K0 ¢§¢§¢§* )¢§RuOH2OU5OH2a a H2O O6U RuOH2OU5OH2a a OH¢§ K1 ¢§¢§¢§* )¢§RuOH2OU4OOHU2a a H2O O7U RuOH2OU4OOHU2a a OH¢§ K2 ¢§¢§¢§* )¢§RuOH2OU3OOHU3 a H2O O8U As no evidence for the existence of oxo-bridged ruthenium(III) complexes was obtained, we propose a mech- anism involving catalytic paths by the hydroxo-aquo ruthe- nium complexes.Ru(H2O)4(OH)2a and Ru(H2O)3(OH)3, because equilibrium (6) is shifted forward considerably under the experimental conditions (K0=1.261011 at 25 8C26). The dependence of reaction rate on [diol] observed suggests the formation of an intermediate complex between the alcohol and the active species of the catalyst. Thus for the species Ru(H2O)4(OH)2a the following can be written: RuOH2OU4OOHU2a a RR0CHOH k1 ¢§¢§¢§* )¢§¢§ k¢§1 C1a a H2O O9U MO analysis31 has shown that the activation energy for hydride transfer from methanol to the oxo ligand of Ru(HN1CH0CH1NH)2(NH3)O2a would be substantially lowered by prior coordination of the substrate to the metal via the hydroxylic oxygen.Such an intermediate complex in J. Chem. Research (S), 1998, 286¡¾287 J. Chem. Research (M), 1998, 1324¡¾1342 *To receive any correspondence (e-mail: abalado@qi¢ç-cr.uclm.es). 286 J.CHEM. RESEARCH (S), 1998Fig. 1 Effect of [Fe(CN)6 3¢§] on the initial rate. [2-Methylpentane-2,4-diol] a 0.08 M; [RuCl3] a 2.4010¢§6 M; I a 0.5 M and T a 30 8C, (a) [NaOH] a 0.28 M; (b) [NaOH] a 0.1 M the Ru(H2O)4(OH)2a reaction with 2-methylpentane-2,4-diol would have the following structure. R is CH30C(CH3)OH0CH2, and R' is CH3 To explain the dependence of v0 on hexacyanoferrate(III) concentration we propose that the ruthenium-substrate complex is attacked by hexacyanoferrate(III) in a slow step (10).This attack involves an outer-sphere one-electron transfer from ruthenium to oxidant and a hydrogen atom transfer from the a-C0H bond to the oxygen of the hydroxo ligand of ruthenium: C1aaFeOCNU6 3¢§ ¢§4 k2 RR0C OH a FeOCNU6 4¢§ a RuOH2OU5OH2a O10U The moderate primary isotope e€ect observed (v0,H/v0,D =5.9) for [2H6]ethane-1,2-diol14 supports the direct involve- ment of the carbon0hydrogen bond in the rate determining step.The experimentally observed presence of free radicals in the reaction mixture and the observation that the oxi- dation of cyclobutanol produces butyraldehyde, would sup- port a hydrogen-atom transfer mechanism. Finally, hexacyanoferrate(III) reacts rapidly with the ketyl radical to yield the reaction products, i.e. 4-hydroxy-4- methylpentan-2-one and hexacyanoferrate(II): FeOCNU6 3¢§ a RR0C OH 4 FeOCNU6 4¢§ a RR0C a OH O11U RR0C a OH a OH¢§ 4 RR0CO a H2O O12U In addition to eqn.(10) we can write for the other active species of the catalyst: RuOH2OU3OOHU3 a RR0CHOH k3 ¢§¢§¢§* )¢§¢§ k¢§3 C2 a H2O O13U C2 a FeOCNU6 3¢§ ¢§4 k4 RR0C OH a FeOCNU6 4¢§ a RuOH2OU4OOHU2a O14U The next step would be similar to that repabove. Hence the disappearance rate of hexacyanoferrate(III) is given by: ¢§daOxa dt a 2k2aC1aaaOxa a 2k4aC2aaOxa O15U where [Ox] is the potassium hexacyanoferrate(III) concen- tration. By applying steady-state hypothesis for both C1a and C2 complexes we obtain: aC1aa a k1aSaaRuOH2OU4OOHU2aa k¢§1 a k2aOxa O16U aC2a a k3aSaaRuOH2OU3OOHU3a k¢§3 a k4aOxa O17U where [S] is the 2-methylpentane-2,4-diol concentration. The total ruthenium(III) concentration may be obtained from the mass balance: aRuIIIaT a aRuOH2OU5OH2aa a aRuOH2OU4OOHU2aa aaRuOH2OU3OOHU3a a aC1aa a aC2a O18U Because of the Hammond postulate,34 it is reasonable to assume that k2/k¢§11k4/k¢§3, that is k¢§1 a k2[Ox]1 b(k¢§3 a k4[Ox]).Substitution of the expressions for [C1a] and [C2] in terms of [RuIII]T into eqn.(15) leads to the reaction rate: ¢§daOxa dt a 2fk1k2K1aOH¢§a a bk3k4K1K2aOH¢§a2gaOxaaSaaRuIIIaT f1 a K1aOH¢§a a K1K2aOH¢§a2g fk¢§1 a k2aOxag a aSafk1K1aOH¢§a a bk3K1K2aOH¢§a2g O26U All experimental results are in complete agreement with the rate eqn. (26). Techniques used: UV, gas chromatography References: 35 Figs: 5 Equations: 26 Received, 9th December 1997; Accepted, 19th February 1998 Paper E/7/08849C References cited in this synopsis 1 E. S. Gore, Platinum Met. Rev., 1983, 27, 111. 2 R. A. Seldon, Bull. Soc. Chim. Belg., 1985, 94, 651. 14 A. Mucientes, F. J. Poblete, M. A. Rodriguez and F. Santiago, J. Phys. Org. Chem., 1997, 10, 647. 17 J. Casado, M. A. LoA pen-Quintela and Barral F. M. Lorenzo, J. Chem. Educ., 1986, 63, 450. 19 M. E. Marmion and K. J. Takeuchi, J. Chem. Soc., Dalton Trans., 1988, 2385. 22 P. T. Speakman and W. A. Waters, J. Chem. Soc., 1955, 45. 23 Cook and Woodworth, J. Am. Chem. Soc., 1953, 75, 6242. 24 K. Meyer and J. RocI ek, J. Am. Chem. Soc., 1972, 94, 1209. 26 W. BoE ttcher, G. M. Brown and N. Sutin, Inorg. Chem., 1979, 18, 1447. 34 G. S. Hammond, J. Am. Chem. Soc., 1955, 77, 334. J. CHEM. RESEARCH (S), 1998 287

ISSN:0308-2342    

DOI:10.1039/a708849c

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Synthesis of Thieno[2',3' : 4,5]pyrimido[2,1-c] [1,2,4]triazoles and Pyrazolylthieno[2,3-d][4,5-d'] dipyrimidines A. A. Geies Chemistry Department, Faculty of Science, Assiut University, Assiut 71516, Egypt 6-Substituted 5-amino-2-hydrazino-4-phenylthieno[2,3-d]pyrimidines (2a�}c) were synthesized and used as key intermediates for the synthesis of new thienopyrimidotriazoles and pyrazolylthienodipyrimidines. In pharmacological studies thieno[2,3-d]pyrimidines and thienodipyrimidines have been shown to possess a variety of pharmacological activities including antituberculous,1 herpes virus inhibitory2 and anti-anaphylactic activity.3 Within this context and also, as part of our research pro- gramme dealing with the synthesis of heterocyclic systems, particularly those containing a thiophene moiety6�}8 we were interested in the synthesis of polyfused heterocycles con- taining these ring systems.The synthesis of the desired compounds began with 5-amino-4-phenyl-6-substituted- 2-(substituted-thio)thieno[2,3-d]pyrimidines (1a�}c), which we have synthesized previously from the reaction of 5-cyano- 6-phenylpyrimidine-2,4(1H,3H)-dithione and a-halo com- pounds.9 Treatment of 1a�}c with hydrazine hydrate in ethanol a€orded the corresponding 2-hydrazino derivatives as a result of extrusion of the �}SCH2COR group. The hydrazino derivatives 2a,b were reacted with triethyl ortho- formate in ethanol containing a few drops of acetic acid and with carbon disulRde in pyridine to give the thienopyrimido- triazoles 3 and 4 respectively.Triazolothione derivatives 4a,b were easily S-alkylated with a-halo compounds to give compounds 5a�}f (Scheme 1). In addition, the hydrazino de- rivatives 2a�}c were condensed with acetylacetone to a€ord the dimethylpyrazolyl derivatives 6a�}c. Alkaline hydrolysis of 6a with alcoholic potassium hydroxide a€orded a com- pound whose 1H NMR spectrum revealed no signals for a dimethylpyrazolyl moiety, this compound was identiRed as 5-amino-6-carboxy-4-phenylthieno[2,3-d]pyrimidin-2(1H)- one (7) which has been synthesized previously9 from the hydrolysis of 1a by alcoholic potassium hydroxide.Compound 7 was boiled under re�Pux in acetic anhydride to give the oxazinone 8, which in turn reacted with ammonium acetate in acetic acid to a€ord the thienodipyrimidine (Scheme 2).9 In addition, when the ester derivative 6a was boiled under re�Pux with hydrazine hydrate in pyridine to synthesize the corresponding carbohydrazide, the pyrazolyl moiety was substituted by a hydrazino group to give 5-amino-2-hydrazino-4-phenylthieno[2,3-d]pyrimidine-6- carbohydrazide 10.Compound 10 reacted with carbon disulRde in pyridine to yield 7-(oxadiazolyl)thienopyrimido- triazole 12, which was easily S-alkylated with 2 equiv. of ethyl chloroacetate to give the dithioester derivative 13. The structure of 12 as an oxadiazole derivative rather than the N-aminopyrimidine derivative 11 was established through the synthesis of the pyrrolyl derivative 14 from the reaction of 12 with 2,5-dimethoxytetrahydrofuran in acetic acid.This compound was also obtained from the reaction of 1a with DMTHF to give compound 15, which when treated with hydrazine hydrate in ethanol gave the carbohydrazide derivative 16. Finally, the reaction of 16 with CS2 in pyridine a€orded a compound that was identical with 14 in mp, mixed mp, elemental analyses and spectral data.On the other hand, compound 6a was condensed with DMTHF in acetic acid to give the corresponding 5-pyrrolyl derivative 17, which in turn could easily be reacted with hydrazine hydrate in ethanol to a€ord the carbohydrazide derivative 18 (Scheme 3). The 1H NMR spectrum of 18 reveals the presence of signals for the dimethylpyrazolyl moiety. The carbohydrazide 18 was reacted with carbon disulRde in pyridine to a€ord the oxadiazolethione 19, which was easily S-alkylated with ethyl chloroacetate in ethanol containing anhydrous sodium acetate to give the J.Chem. Research (S), 1998, 290�}291 J. Chem. Research (M), 1998, 1248�}1263 Scheme 1 290 J. CHEM. RESEARCH (S), 1998Scheme 2 Scheme 3 Scheme 4 thioester derivative 20. 5-Aminocarboxamide 6c was con- densed with triethyl orthoformate in ethanol in the presence of a few drops of acetic acid and with acetic anhydride to give thienodipyrimidines 21 and 22 respectively (Scheme 4).Finally, 6c was reacted with carbon disulRde in pyridine to give the pyrimidinethione 23 which was S-alkylated with ethyl chloroacetate to a€ord the thioester derivative 24. Techniques used: IR, 1H NMR, elemental analysis; Refs: 9 Schemes: 4; Tables: 1 Received, 9th June 1997; Accepted, 9th February 1998 Paper E/7/03982D References cited in this synopsis 1 N. N. Kaplina, V. L. Shedov, L. N. Filitis, U.S.S.R. 1993, SU1, 383, 752 (Chem. Abstr., 1995, 123, 228206r). 2 N. N. Kaplina, V. L. Shedov, A. N. Fomina, I. S. Nikolaeva, T. V. Pushkina, L. N. Filitis, U.S.S.R., 1993, SU1, 389, 235 (Chem. Abstr., 123, 275971w). 3 G. Wagner, H. Vieweg and S. Leistner, Pharmazie, 1993, 48, 667. 6 A. A. Geies, A. A. Abdel-Hafez, J. C. Lancelot and H. S. El-Kashef, Bull. Chem. Soc. Jpn., 1993, 66, 3716. 7 H. S. El-Kashef, A. A. Geies, A. M. Kamal El-Dean and A. A. Abdel-Hafez, J. Chem. Tech. Biotechnol., 1993, 57, 15. 8 A. A. Geies, Pharmazie, 1997, 52, 500. 9 Z. H. Khalil and A. A. Geies, Phosphorus Sulfur Silicon, 1991, 60, 223. J. CHEM

ISSN:0308-2342    

DOI:10.1039/a703982d

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Naturally Occurring Prenylated Phthalides: First Total Synthesis of Salfredin B11 Raghao S. Mali* and Kantipudi N. Babu Department of Chemistry, Garware Research Centre, University of Pune, Pune-411007, India Convenient syntheses of salfredin B11 (1) and dihydrophthalidochromene (14b), from hydroxyphthalides (7 and 10), are described. A few prenylated phthalides and their derivatives have been reported from natural sources. Salfredin B11 (1), for example, has been isolated1 from the fermentation broth of Crucibulum sp.RF-3817, and phthalidochromene2 (2) and platypterophthalide2 (3) from the roots of Helichrysum platypterum. Another prenylated phthalide arenophthalide A (4), has been reported from the roots of H. arenarium.3 These prenylated phthalides are valuable as they possess signi®cant biological activities. Thus salfredin B11 (1) has aldose reductase inhibitor activity,1,5 while arenophthalide A (4) has antibacterial properties.3 The syntheses of salfredin B11 (1) and phthalidochromene (2) have not been reported so far in the literature.In view of the impressive biological activities exhibited by prenylated phthalides, in general, and salfredin B11 (1) and phthalido- chromene (2), in particular, it was decided to develop convenient methods for their syntheses. The present approach developed for the synthesis of salfredin B11 (1), is depicted in Scheme 1. The dihydroxy- phthalide 7 was monoprop-2-ynylated using 3-chloro-3- methylbut-1-yne in DMF solution in the presence of K2CO3, KI and CuI at 60 8C to give the prop-2-ynyl ether 8.The ether 8, on heating in N,N-dimethylaniline solution at 210 8C, provided salfredin B11 (1), in 62% yield. The yield of 1 was improved to 82% when the reaction was carried out under microwave irradiation (MWI) for 3 min. The IR and NMR spectral properties exhibited by com- pound 1 are identical with those of natural salfredin B11. The approach developed for the synthesis of dihydro- phthalidochromene (14b) is shown in Scheme 2. 7-Hydroxy- 5-methoxyphthalide7 (10), on prenylation using 4-bromo-2- methylbut-2-ene, in DMF solution, gave the prenyl ether 11 in 92% yield. The prenyl ether 11 on heating in N,N-dimethylaniline at 210 8C for 22 h, gave the 4-prenyl- phthalide (12) in 61% yield, which on reaction with pyridine hydrochloride at 180 8C for 1 h provided the dihydro- pyranophthalide (14a) in 53% yield. Methylation of 14a, using methyl iodide, furnished the dihydrophthalido- chromene 14b in 85% yield.The synthesis of 6-allyl-5,7-dimethoxyphthalide (6b) has also been achieved as shown in Scheme 2. When the allyloxy phthalide 15, obtained in 92% yield by allylation of 10, was heated at 210 8C, in N,N-dimethylaniline solution for 4 h, 6-allyl-7-hydroxy-5-methoxyphthalide (6a) was obtained in 82% yield. The methylation of 6a to obtain 6b was achieved using methyl iodide. 6-Allyl-5,7-dimethoxyphthalide (6b), an intermediate used for the synthesis of hericenone A analogues (5b), has been synthesized earlier6 using a multi- step reaction sequence.In the present work its synthesis has been achieved in three steps from the phthalide 10 (Scheme 2). In conclusion, the present paper describes convenient methods for the syntheses of salfredin B11 (1), dihydro- phthalidochromene (14b) and 6-allyl-5,7-dimethoxyphthalide (6b), which is a useful intermediate for hericenone A analogues. J. Chem.Research (S), 1998, 292±293 J. Chem. Research (M), 1998, 1215±1229 Scheme 1 Reagents and conditions: i, 3-chloro-3-methylbut- 1-yne, K2CO3, KI, CuI, DMF, 60 8C, 4 h; ii, PhNMe2, 210 8C, 6 h or MWI, 3 min Scheme 2 Reagents and conditions: i, 4-bromo-2-methylbut- 2-ene, K2CO3, DMF, room temp. 6 h; ii, PhNMe2, 210 8C, 22 h or MWI, 11 min; iii, Py±HCl, 180 8C, 1 h; iv, MeI, K2CO3, DMF, room temp., 1 h; v, 3-bromopropene, K2CO3, DMF, room temp., 6 h; vi, PhNMe2, 210 8C, 6 h *To receive any correspondence (e-mail: rsmali@chem.unipune. ernet.in). 292 J. CHEM. RESEARCH (S), 1998The authors are grateful to Professor N. S. Narasimhan for critical reading of the manuscript and valuable sugges- tions. K. N. B. thanks CSIR, New Delhi for the award of a Senior Research Fellowship. Financial support from CSIR, New Delhi, is gratefully acknowledged. Techniques used: IR, 1H NMR, elemental analyses, TLC and column chromatography References: 10 Figures: 3 Received, 28th October 1997; Accepted, 12th February 1998 Paper E/7/07767J References cited in this synopsis 1 K. Matosumoto, K. Nagashima, T. Kamigauchi, Y. Kawamura, Y. Yasuda, K. Ishii, N. Uotani, T. Sato, H. Nakai, Y. Terui, J. Kikuchi, Y. Ikenisi, T. Yoshida, T. Kato and H. Itazaki, J. Antibiot., 1995, 48, 439. 2 J. Jakupovic, A. Schuster, H. Sun, F. Bohlmann and D. S. Bhakuni, Phytochemistry, 1987, 26, 580. 3 J. Vrkoc, M. Budesinsky, L. Dolejs and S. Vasickova, Phyto- chemistry, 1975, 14, 1845. 5 (a) M. Nishikawa, Y. Turumi, H. Murai, K. Yoshida, M. Okamoto, S. Takase, H. Tanaka, H. Hirota, M. Hashimoto and M. Kohsaka, J. Antibiot., 1991, 44, 130; (b) K. Ozasa, T. Oneda, M. Hirasawa, K. Suzuki, K. Tanaka, S. Kadota and M. Iwanami, J. Antibiot., 1991, 44, 768. 6 A. V. Rama and R. G. Reddy, Tetrahedron Lett., 1992, 31, 373. 7 R. S. Mali, P. G. Jagtap and S. G. Tilve, Synth. Commun., 1990, 20, 2841. J. CHEM. RESEARCH (S), 1998 293

ISSN:0308-2342    

DOI:10.1039/a707767j

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Methylheteroaromatic Carbonitriles as BuildingBlocks for Synthesis of Condensed Heteroaromatics:Novel Syntheses of [1]Benzo[2,3]pyrano[3,4-c]-pyridines, Naphtho[2',1':5,6]pyrano[3,4-c]pyridines,Pyrido[3,4-c]quinolines and Other New CondensedPyridinesFatima Al-Omran,a Mervat Mohammed Abdel-Khalik,bAdel Abou El-khaira and Mohammed Hilmy Elnagdi*aaDepartment of Chemistry, Faculty of Science, Kuwait University of Kuwait, P.O. Box 5969,Safat 13060, KuwaitbDepartment of Chemistry, College For Girls, Ain Shams University, Heliopolis, Cairo, EgyptA variety of condensed pyridines were prepared via condensing alkylheteroaromatic carbonitriles with N,N-dimethylformamidedimethylacetal and subsequent cyclization of the formed products.In conjunction with previous work we report hereon the utility of the methylheteroaromatic carbonitriles1a, b, 2 and 3 as building blocks for the synthesis ofcondensed pyridines.Thus compounds 1a, b and 2 con-densed with dimethylformamide dimethylacetal (DMFDMA) to yield the (E)-dimethylaminoethylene derivatives4a, b and 5.Compounds 4a, b and 5 were assigned the(E) structure based on 1H NMR, which revealed ethyleneprotons as two doublets at d 5.7 and d 8.5 ppm withJ 13 Hz.The reaction of 3 with DMF DMA in reuxingxylene aorded a xylene-insoluble product and a xylenesoluble one in a 3:1 ratio. The xylene-soluble productwas identied as the (E)-dimethylaminoethylene quinolinederivative 6 while the xylene-insoluble part proved to bethe amidine derivative 7.Structures 6 and 7 were assignedto these products based on spectral data. Thus the IRspectrum of 6 revealed the presence of an NH2 absorption.The 1H NMR spectrum of 6 did not exhibit a methylgroup signal but showed two one-proton doublets atd 6.51 and d 8.11 ppm with J 13 Hz, for the transolenic protons. The 1H NMR spectrum of 7 exhibited amethyl group signal at d 2.82 ppm and the absenceof the D2O exchangeable amino signal at d 8.57 ppm.It showed, in addition to the ¡ÓNMe2 signal, an aromaticmultiplet, and a singlet at d 8.62 ppm for the imino-methylene proton.Compounds 4a, b, 5 and 6 were converted into thepyridone derivatives 8a, b, 9a and 10 upon reux in aceticacid in the presence of concentrated hydrochloric acid.We believe that under these reaction conditions the cyanofunction is rst hydrolysed into the corresponding amidewhich then adds to the activated double bond, aording atetrahydropyridine that then undergoes aromatization vialoss of dimethylamine (Chart 1).Compound 4a, b were converted into the (E)-anilino-ethylene derivatives 4c, d on treatment with aniline.Theisomeric cyclic structures 8c, d were readily ruled out on thebasis of IR spectra that revealed, in each case, a cyanogroup signal at max12180 cm£¾1. Moreover the 1H NMRspectra indicated the presence of trans olenic protondoublets at d 6.3 and d 8.4 ppm with J 13 Hz. Boiling 4c,d under reux in DMF for 5 min resulted in their cyclizationinto 8c, d.It is believed that under such conditionsthe double bond is rst isomerized into the (Z) form,which then cyclizes into 8c, d. Similar treatment of 5J. Chem. Research (S),1998, 294¡Ó295J. Chem. Research (M),1998, 1201¡Ó1214Chart 1 *To receive any correspondence.294 J. CHEM. RESEARCH (S), 1998with aniline a€orded directly the N-phenylnaphthopyrano- pyridine derivative 9b. Attempted acylation of 6 resulted in the formation of a product of molecular formula C14H9N3O; m/z (%): 235 (50) [Ma].This was thus assigned structure 14. It is assumed that initially formed 11 cyclizes into 12 which then cyclizes further into 13 which loses dimethylamine, yielding 14 (Chart 2). This, to our knowledge, is the Rrst reported example of this ring system. The 13C NMR spectrum of this product is in complete agreement with the proposed struc- ture. Previously we have established that alkylazinylcarbo- nitriles react with sulfur in the presence of a base to yield thienoazines7 which add to electron-poor oleRns and acetylenes to yield (4 a 2) cycloadducts that either decom- pose into benzo fused heteroaromatics or rearrange to con- densed thiepins.4�}6 It was thus thought worthwhile to investigate the behaviour of the quinolines 3 and 7 in similar reactions.Under a variety of conditions compound 3 did not react with elemental sulfur, while 7 reacted smoothly with sulfur in DMF solution in the presence of piperidine to yield a product of molecular formula C12H7N3S; m/z (%): 225 (100) [Ma].This was thus assigned structure 16 and is assumed to be formed via intermolecular cyclization of intermediate 15. Attempts to isolate 15 failed. Compound 16 failed to add to both electron-poor oleRns and acetylenes. This work is Rnanced by the University of Kuwait research grants SC 082 and SC 089. We are grateful to the University of Kuwait general facility projects in the Chemistry Department for the analytical and spectral measurements. Techniques used: IR, 1H NMR, 13C NMR, MS and elemental analysis References: 8 Charts: 2 Received, 22nd May 1997; Accepted, 16th February 1998 Paper E/7/03549G References cited in this synopsis 6 F. Al-Omran, M. M. Abdel Khalik, H. Al-Awadhi and M. H. Elnagdi, Tetrahedron, 1996, 52, 11915. 7 M. H. Elnagdi, A. M. Negm and K. Y. Sadek, Synlet, 1994, 27. 8 E. Nyiondi-Bonguen, E. Sopbue Fondjo, Z. Tanee Fomum and D. DoE pp, J. Chem. Soc., Perkin Trans. 1, 1994, 2191. Chart 2 J. CHEM. RESEARCH (S), 1998 2

ISSN:0308-2342    

DOI:10.1039/a703549g

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Conformational Analysis of N-Methylpyrrolidine Betaine Hydrochloride by X-Ray Diffraction and Ab Initio Calculations Zofia Dega-Szafran, Mal/gorzata Ratajczak-Sitarz, Lucyna Prawniczak, Zofia Kosturkiewicz, Jacek Koput and Mirosl/aw Szafran* Faculty of Chemistry, A. Mickiewicz University, 60780 Poznan¡� , Poland The structure of the title compound in the solid state and its five most stable conformers in the gas phase have been analysed by X-ray diffraction, and by MP2/6-31G(d,p) and BLYP/6-31G(d,p) calculations, respectively.We report here the e€ect of the attractive Coulombic interaction between the two oppositely charged groups in N-methylpyrrolidine betaine hydrochloride, MPRBETHCl, on its conformation in the solid state and the gas phase. X-Ray Di€raction.�¢X-Ray data were collected on a KUMA-4 di€ractometer. MPRBETHCl has a monoclinic space group, P21/c, Z a 4, a a 6.750(1), b a 11.502(2), c a 12.146(2) A E , a 109.36(3)8, V a 889.7(3) A E 3, R a 0.036, CuK radiation ( a 1.54178 A E ). The structure was solved by direct methods using SHELXS-8633 and re¢çned by the SHELXL-9334 program.Non-hydrogen atoms were located from an E-map and re¢çned anisotropically. The positions of the hydrogen atoms were found from a di€erence Fourier map, except those of H(31) and H(32), which were located from geometrical considerations. The investigated betaine is protonated and the carbonyl group forms a H-bond with the chloride ion; O Cl distance is 2.893(3) A E .The nitrogen atom is above the ring carbon atoms and CH2COOH moiety is in the axial position. The torsion angles of N¡¾CH2¡¾C¡¾O(H) and the N¡¾CH2¡¾C1O are 6.5(3) and ¢§174.2(2)8, respectively. Fig. 2 shows a perspective view of MPRBETHCl and contacts of the chloride ion. The intramolecular N(1) Cl distance is 5.706(3) A E , while the intermolecular distances are much shorter [4.068(2) A E (symmetry code x; 0.5 ¢§ y; 0.5 a z), 4.105(2) (x; 0.5 ¢§ y; 0.5 a z), 4.756(2) A E (1 ¢§ x; ¢§y; 1 ¢§ z) and 4.939(2) A E (1 ¢§ x; ¢§0.5 a y; 1.5 ¢§ z)].The NaCH2COOH moiety is structurally similar to those in other betaine chlorides, with the excep- tion that the oxygen atoms have opposite positions (Table 4). Ab Initio Calculations.�¢The ab initio calculations were performed with the GAUSSIAN-94 program package.36 The molecular parameters were optimized at the MP2/6- 31G(d,p) and BLYP/6-31G(d,p) levels of theory.Fig. 3 shows the ¢çve most stable conformers of MPRBETHCl. Table 5 gives the dipole moments, total and relative energies. In all conformers (I¡¾V) the pyrrolidine ring forms an envelope. In conformers I, IV and V the nitrogen atom is above the ring plane while in conformers II and III the C(3) atom is above the ring plane (Fig. 3). From Table 5, evidently conformer IV represents the global minimum in the gas phase. This type of conformer is also the most stable for N,N-dimethylglycine (DMG).11 Although, the most stable conformers in MPRBETHCl and DMG are comparable, they are stabilized by di€erent forces.In DMG the intermolecular N H¡¾O hydrogen bond is very signi¢çcant to the stability of the conformers. In MPRBETHCl the CO2H group can form a hydrogen bond only with the chloride ion, because the quaternary nitrogen atom has no lone-pair. As Fig. 3 shows, IV conformer is stabilized by two interactions, the attractive Coulombic interaction of the chloride ion with the positively charged nitrogen atom and the Cl H¡¾O hydrogen bond.The electrostatic interactions decrease the proton acceptor properties of chloride ion and as a result a proton transfer takes place in the gas phase. Amines (pKa=10.5¡¾10.9) with J. Chem. Research (S), 1998, 296¡¾297 J. Chem. Research (M), 1998, 1264¡¾1280 Fig. 2 Perspective view showing contacts of the chloride ion in C4H8Na(CH3)CH2CO2HCl¢§ Table 4 Comparison of X-ray-determined bond lengths (A ), bond angles (8) and torsion angles (8) in some related betaine hydrochlorides O(H) Cl¢§ C¡¾O(H) C1O C¡¾C¡¾O(H) C¡¾C1O (H)O¡¾C1O N¡¾CH2 ¡¾C¡¾O(H) N¡¾CH2¡¾C1O Space group C4H8NaMeCH2CO2HCl¢§ 2.893(3) 1.308(3) 1.204(3) 116.7(2) 118.6(2) 124.7(2) 6.5(3) ¢§174.2(2) P21/c Me3NaCH2CO2HCl¢§ a 2.955(2) 1.316(2) 1.193(2) 109.0(2) 126.0(2) 125.1(2) 173.3(1) ¢§7.0(3) P21/c Me3NaCH2CO2HCl¢§ b 2.946(3) 1.322(4) 1.199(6) 107.9(3) 126.6(3) 125.4(4) ¢§180.0 0.0 Cm C5H5NaCH2CO2HCl¢§ c 2.928(3) 1.130(3) 1.189(3) 110.4(2) 125.8(2) 123.8(2) 178.6(2) ¢§1.1(3) P21/c Et3NaCH2CO2HCl2H2Od 1.291(6) 1.197(5) 109.6(4) 125.2(5) 125.1(5) ¢§167.2(4) 13.3(7) P21/n aData from ref. 43; bdata from ref. 44; cdata from ref. 45; ddata from ref. 46. *To receive any correspondence. 296 J. CHEM. RESEARCH (S), 1998hydrochloride form simple hydrogen bonded complexes (R3N HCl), without proton transfer in the gas phase,51 even though they are stronger bases than MPRBET (pKa=1.92). Conformer II is less stable than IV by 4.46 kcal mol¢§1 and 5.72 kcal mol¢§1, respectively, at the BLYP and MP2 levels, whereas the remaining conformers di€er by more than 9 kcal mol¢§1.In conformers I, III and V the proton is closer to the chloride ion and the COO H species has the more stable syn (cis) arrangement.52 In more stable conformers (IV and II) the carboxylate group has an anti (trans) con- formation. In formic acid the anti conformer is less stable than the syn conformer by 6 kcal mol¢§1.52 As Tables 3 and 5 show, when the N Cl distance increases the relative energy also increases.The lowering of the attractive Coulombic interaction between nitrogen and chloride atoms is compensated by the interaction between the nitrogen and oxygen atoms. Comparing the X-ray data with the calculations it seems that conformer I most closely resembles that in the crystal (Table 3), except for the H-bonded proton position.M. S. and Z. D-S. thank the Polish State Committee of Scienti¢çc Research (Grant 2P303 06907) for ¢çnancial sup- port and the PoznanA Supercomputing and Networking Centre for computing time. Techniques used: X-ray di€raction, MP2/6-31G(d,p) and BLYP/ 6-31G(d,p) calculations References: 52 Tables 1¡¾3, 6, 7: Crystal data, atomic coordinates, bond lengths, bond angles, torsion angles and thermal parameters Fig. 1: Molecular structure and atom labelling of N-methylpyrroli- dine betaine hydrochloride Received, 11th November 1997; Accepted, 9th February 1998 Paper E/7/08102B References cited in this synopsis 11 A.D. Headley and S. D. Starnes, J. Mol. Struct. (Theochem), 1996, 370, 147. 33 G. M. Sheldrick, SHELXS-86. Program for the Solution of Crystal Structures, University of GoE ttingen, Germany, 1986. 34 G. M. Sheldrick, SHELXL-93. Program for the Re¢çnement of Crystal Structures, University of GoE ttingen, Germany, 1993. 36 M. J. Frisch, G. W. Trucks, M.Head-Gordon, P. M. W. Gill, M. W. Wong, J. B. Foresman, B. G. Johnson, H. B. Schlegel, M. A. Robb, E. S. Replogle, R. Gomperts, J. L. Andres, K. Raghavachari, J. S. Binkley, C. Gonzalez, R. L. Martin, D. J. Fox, D. J. Defrees, J. Baker, J. J. P. Stewart, J. A. Pople, Gaussian 94, Revision B, Gaussian, Inc., Pittsburgh, PA, 1994. 43 M. S. Fischer, D. M. Templeton and A. Zalkin, Acta Crystallogr., Sect. B, 1970, 26, 1392. 44 W. H. Yip, Wang Ru-JI and T. C. W. Mak, Acta Crystallogr., Sect.C, 1990, 46, 717. 45 M. Szafran, J. Koput, J. Baran and T. Gl/owiak, J. Mol. Struct., 1997, 436¡¾437, 123. 46 Huang Wei-Yuan, Du Xue-Mei, Yang Bing-Hua and T. C. W. Mak, J. Mol. Struct., 1990, 222, 479. 51 A. C. Legon, Chem. Soc. Rev., 1993, 153. 52 S. M. Cybulski and S. Scheiner, J. Am. Chem. Soc., 1989, 111, 23. Fig2/6-31G(d,p) optimized structures of C4H8Na(CH3)CH2CO2HCl¢§ Table 5 Total energy (E/hartreea), relative energies (Erel/kcal mol¢§1), dipole moment (m/debye), selected distances (A ) and dihedral angles (8) for conformers I¡¾V of the 1-(carboxymethyl)-1-methylpyrrolidinium chloride, MPRBETHCl Conformer E Erel m O Cl Na Cl O H H Cl O1C¡¾O¡¾H BLYP I ¢§940.350577 9.42 15.49 2.916 5.735 1.538 1.389 0.0 II ¢§940.358167 4.46 14.24 2.855 4.569 1.105 1.754 ¢§178.7 III ¢§940.350442 9.51 16.27 2.922 6.345 1.533 1.393 ¢§41.8 IV ¢§940.365592 0 10.65 2.977 3.726 1.045 1.946 ¢§169.8 V ¢§940.350074 9.74 17.03 2.921 6.355 1.532 1.393 0.5 MP2 I ¢§938.548967 9.96 15.87 2.947 5.723 1.630 1.326 ¢§1.5 II ¢§938.555720 5.72 15.13 2.820 4.464 1.065 1.761 ¢§179.9 III ¢§938.549633 9.54 16.13 2.962 6.259 1.640 1.325 0.02 IV ¢§938.564831 0 11.43 2.972 3.615 1.014 1.970 ¢§172.9 V ¢§938.548181 10.45 17.06 2.957 6.277 1.634 1.326 ¢§0.2 a1 hartree a 627.72 kcal mol¢§1. J. CHEM. RESEARCH (S), 1998 297

ISSN:0308-2342    

DOI:10.1039/a708102b

出版商:RSC    

年代:1998

数据来源: RSC