摘要:

N N R O R¢¢ R¢ O N N P R O R¢¢ R¢ O O OEt OEt P(OEt)3 CH2Cl2 N N R O R¢¢ R¢ O P OEt OEt O + 1 3 4 N N Br R O R¢¢ R¢ O 2 NBS, AlBN CCl4 N N R O R¢¢ R¢ O 5 i, NaH, ii, paraformaldehyde R = R¢¢ = Me, R¢ = H R = R¢ = R¢¢ = Me R = Me, R¢ = H, R¢¢ = Ac R = R¢ = Me, R¢¢ = Ac R = R¢¢ = Ac, R¢ = H R = R¢¢ = Ac, R¢ = Me 1a–3a, 5a 1b–3b, 5b 1c–3c, 5c 1d–3d, 5d 1e–4e 1f–2f, 4f 382 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 382 J. Chem. Research (M), 1997, 2347–2357 Regioselective Routes to Functionalised Piperazine- 2,5-diones Christina L.L. Chai*a,b and Alison R. Kingb aDepartment of Chemistry, The Faculties, Australian National University, ACT 0200, Australia bResearch School of Chemistry, Australian National University, ACT 0200, Australia The regioselectivities observed in the reactions of bromopiperazine-2,5-diones with triethyl phosphite depend markedly on the N-substituents a to the brominated carbon atom. The competing reactions of phosphite esters with a-haloketones to give phosphonate esters or vinyl phosphates have long been realised.6,7 The former product results from the direct nucleophilic displacement of the halogen by the phosphorus atom of the phosphite ester onto the a-carbon atom (Michaelis–Arbuzov reaction).2 In contrast, the isomeric vinyl phosphate is most likely formed via nucleophilic substitution onto the carbonyl carbon (Perkow reaction).The regioselective control of the reaction depends on the reaction conditions as well as the nature of the leaving group.6,7 In comparison to the a-haloketones, the reactions of a-halo- a-amino acids and their derivatives with phosphite esters yield the synthetically useful phosphonate ester.3 Surprisingly there are no reports on the formation of the Perkow product from a-halo-a-amino acids under similar conditions.In our quest to develop synthetic routes to functionalised piperazine- 2,5-diones (cyclic dipeptides), we discovered that the choice of mechanisms can be controlled by the subtle change in the nature of the N-substituents a to the halogen atom.This is summarised in the Scheme. In cases where the bromine group is a to an N-methyl substituent (piperazinediones 2a–2d, the usual Michaelis–Arbuzov products (piperazinediones 3a–3d are formed. In contrast, in cases where the bromine atom is a to an N-acetyl substituent (piperazinediones 2e,2f, the Perkow reaction predominates and vinyl phosphates (piperazinediones 4e,4f are obtained.The regiocontrol observed in these cases may be attributed to the differing electronic properties of the adjacent nitrogen atom. The ability to control the outcome of reactions in this manner is of synthetic significance. For example, the phosphonate esters 3a–3d can be converted to the previously unknown 1-methyl-6-methylenepiperazine-2,5-diones 5a–5d under Wittig–Horner olefination conditions. These methylene piperazine-2,5-diones are important synthetic precursors for further chemical elaboration.13 Techniques used: 1H, 13C, 31P NMR References: 14 Schemes: 3 Table 1: Yields of phosphonate esters, vinyl phosphates and methylene compounds are summarised Received, 7th May 1997; Accepted, 23rd July 1997 Paper E/7/03155F References cited in this synopsis 2 A.K. Bhattacharya and G. Thyagarajan, Chem. Rev., 1981, 81, 415. 3 (a) R. Kober and W. Steglich, Liebigs Ann. Chem., 1983, 599; (b) K. Burger, E. Heistracher, R. Simmerl and M. Eggersdorfer, Z. Naturforsch., Teil B, 1992, 47, 424. 6 P. A. Chopard, V. M. Clark, R. F. Hudson and A. J. Kirby, Tetrahedron, 1965, 21, 1961. 7 For examples, see (a) J. F. Allen and O. H. Johnson, J. Am. Chem. Soc., 1955, 77, 2871; (b) H. I. Jacobson, M. J. Griffin, S. Preis and E. V. Jensen, J. Am. Chem. Soc., 1957, 79, 2608. 13 C. L. L. Chai and A. R. King, Tetrahedron Lett., 1995, 36, 4295. *To receive any correspondence (e-mail: christina.chai@anu. edu.au). Scheme

ISSN:0308-2342    

DOI:10.1039/a703155f

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N Z S H N Z S R N Z S R 6, 8 and 10 PhCH CHCH2OCO2Et 4a CH2 CHCH2OCO2Me 4b + Pd0/L THF Pd0/L THF, heat or THF, 25 °C, 24 h or THF–H2O 5, 6; Z = O 7, 8; Z = S 9,10; Z = NH a, R = Ph b, R = H 1 Z = O 2 Z = S 3 Z = NH or 5, 7 and 9 J. CHEM. RESEARCH (S), 1997 383 J. Chem. Research (S), 1997, 383 J. Chem. Research (M), 1997, 2308–2317 Regioselective S- or N-Palladium(0) Catalysed Allylation of Five-membered Heterocyclic Ambident Sulfur Nucleophiles Catherine Goux, Silvana Sigismondi and Denis Sinou* Laboratoire de Synth`ese Asym�etrique, associ�e au CNRS, CPE Lyon Universit�e Claude Bernard Lyon I, 43, boulevard du 11 Novembre 1918, 69622 Villeurbanne C�edex, France Palladium(0)-catalysed allylation of benzoxazolethione, benzothiazolethione and benzimidazolethione in dry THF occurs at sulfur, whereas in THF–water the allylation occurs at nitrogen.Palladium(0)-catalysed allylation of nucleophiles is a versatile synthetic method in organic chemistry and control of the selectivity is a topic of great interest.1,5,12,13 Although this methodology has been used in the allylation of heterocyclic systems leading to carbanucleosides and nucleosides, some regioselectivity problems were observed, particularly in the uracil and thiouracil families.18,21,29,30 We now report that the regioselectivity of the allylation (N vs.S-allylation) of benzoxazolethione 1, benzothiazolethione 2 and benzimidazolethione 3 depends on the reaction time, the temperature, the solvent used (and particularly the water content) and the nature of the allylating reagent. The reaction of compounds 1–3 with cinnamyl ethyl carbonate in the presence of palladium(0) complexes in dry THF at 25 °C gave as the main products compounds 5a, 7a and 9a resulting from allylation at the sulfur.However, the use of mixtures of H2O–THF or performing the reaction at 60 °C also allowed the formation of products 6a, 8a and 10a resulting from the allylation at the nitrogen, together with the products of allylation at sulfur.The reaction of compounds 1–3 with allyl methyl carbonate in the presence of palladium(0) complexes was more complex. At low temperature and in dry THF the products 5b and 7b resulting from allylation at sulfur were also formed after 2 h in the case of benzoxazolethione 1 and benzothiazolethione 2. However, when the reaction was performed in dry THF at room temperature for 24 h or at 60 °C in THF for 2 h, only the products of allylation at nitrogen were observed.In the case of benzimidazolethione 3, the product of N-allylation 10b was formed under these two conditions. Using H2O–THF mixtures gave the products of N-allylation and of S-allylation. In the presence of a palladium catalyst in THF–H2O as the solvent, the products of S-allylation 5a, 7a and 9a were transformed smoothly into the thermodynamic N-allylated compunds. Techniques used: 1H and 13C NMR References: 30 Schemes: 3 Table 1: Pd0-catalysed reactions of benzoxazole-2(3H)-thione 1 with allyl carbonates 4 Table 2: Pd0-catalysed reactions of benzothiazole-2(3H)-thione 2 with allyl carbonates 4 Table 3: Pd0-catalysed reactions of 1,3-dihydrobenzimidazole- 2-thione 3 with allyl carbonates 4 Table 4: Pd0-catalysed isomerisation of cinnamyl derivatives 5a, 7a and 9a Received, 18th March 1997; Accepted, 21st July 1997 Paper E/7/01885A References cited in this synopsis 1 B.M. Trost and T. R.Verhoeven, Comprehensive Organometallic Chemistry, ed. G. Wilkinson, F. G. A. Stone and E. W. Abel, Pergamon Press, New York, 1982, vol. 8, p. 799. 5 S. A. Godleski, Comprehensive Organic Synthesis, ed. B. M. Trost, Pergamon Press, Oxford, 1991, vol. 4, p. 585. 12 J. Tsuji, Palladium Reagents and Catalysts; Innovations in Organic Synthesis, Wiley, Chichester, 1995. 13 P. J. Harrington, Comprehensive Organometallic Chemistry II, ed. E. W. Abel, F. G. A. Stone and G. Wilkinson, Pergamon, Oxford, 1995, vol. 12, p. 797. 18 L.-L. Gundersen, T. Benneche, F. Rise, K. Gogoll and K. Undheim, Acta Chem. Scand., 1992, 40, 761. 21 M. Moreno-Ma�nas, R. Pleixats and M. Villarroya, Tetrahedron, 1993, 49, 1457. 29 S. Sigismondi, D. Sinou, M. P�erez, M. Moreno-Ma�nas, R. Pleixats and M. Villarroya, Tetrahedron Lett., 1994, 35, 7085. 30 C. Goux, S. Sigismondi, D. Sinou, M. P�erez, M. Moreno-Ma�nas, R. Pleixats and M. Villarroya, Tetrahedron, 1996, 52, 9521. *To receive any correspondence. Scheme Table Examples of palladium(0)-catalysed reactions of heterocyclic ambident sulfur nucleophiles 1–3 with allylic carbonates 4a–b Substrate Carbonate Solvent T/°C (t/h) Products (yield %) 1 4a THF THF–H2O 25 (16) 60 (24) 5a (78)+6a (3) 5a (57)+6a (7) 4b THF THF 25 (2) 60 (2) 5b (91)+6b (9) 6b (95) 2 4a THF THF–H2O 25 (16) 60 (60) 7a (52) 7a (71)+8a (28) 4b THF THF 25 (4) 60 (4) 7b (97) 8b (90) 3 4a THF THF–H2O 25 (16) 60 (24) 9a (36) 10a (60) 4b THF THF 5 (24) 25 (3) 9b (5)

ISSN:0308-2342    

DOI:10.1039/a701885a

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

O O NH2 Cl 1 4 O O NH2 O 1 4 R 1¢ 4¢ HOC6H4R –HCl NH2 O O O 1 4 R hn l 300–480 nm hn l > 520 nm para-2/ ana-2 a R = H b R = OMe c R = CH2OH d R = [CH2]2OH e R = [CH2]4OH 1 para-2 ana-2 O O NH2 O [CH2] nOH 1 4 1¢ 4¢ O O NH2 O [CH2] nO 1 4 1¢ O para-2d n = 2 e n = 4 4d n = 2 e n = 4 + CH2C(Me)C(O)Cl + Et3N, –Et3N•HCl O O NH2 O [CH2]2O O O NH O [CH2]2O 4¢¢ 1¢¢ 4¢ 1¢ 4d + CH2C(Me)C(O)Cl + Et3N, –Et3N•HCl O 5 O O Cl 1 4 O [CH2] n O CO [CH2] n O Me O CO O O O H2N O O H2N l 300–480 nm l > 520 nm ~8 poly-4d n = 2 e n = 4 AIBN 1 O orange blue 386 J.CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 386–387 J. Chem. Research (M), 1997, 2318–2346 Quinones. Part 16.† 1-Amino-4-(4-hydroxyalkylphenyl)- and 1-Amino-4-(w-hydroxyalkoxy)-9,10-anthraquinones for Photochromic Methacrylate Polymers Peter Boldt,*a Stephan Zippela and Gerd Hauckeb aInstitut f�ur Organische Chemie, D-38092 Braunschweig, Germany bInstitut f�ur Physikalische Chemie, Friedrich-Schiller-Universit�at Jena, Philosophenweg 14, D-07743 Jena, Germany Polymethacrylates with photochromic anthraquinonoid side chains are prepared.Photochromic materials have been investigated widely for use in imaging, holography and optical data recording.1 The photoisomerization of the orange-red para quinonoid 1-amino-4-phenoxy-9,10-anthraquinone (para-2a) to the blue ana quinonoid 4-amino-9-phenoxy-1,10-anthraquinone (ana-2a) and vice versa shows a high cyclicity.2 Similar investigations have been reported in the naphthacenequinone series.3 These compounds also show a large colour shift and thermal stability of both photoisomers.5 However, a polymeric photochromic system based on the reversible photoisomerization para-2aMana-2a seemed to be attractive with respect to the easy synthetic access and the good solubility. We functionalized the 4-position of the phenoxy group with a hydroxy group or with w-hydroxyalkyl-spacers of different lengths (para-2c–e) in order to attach these photochromic molecules to a polymeric methacrylate backbone.The syntheses of para-2b–e were accomplished in moderate yields by heating 1-amino-4-chloro-9,10-anthraquinone (1) in a phenol–phenolate melt of the corresponding phenols (Scheme). The blue coloured ana-anthraquinones ana-2b,d and e were obtained (7–17%) by irradiation of the orange-red benzene solutions of para-2b,d and e with light of l 310–460 nm. Compounds ana-2b,d and e proved to be thermally stable.The reverse photoisomerization could be effected quantitatively by irradiation with light of l 577 nm. The methacrylates 4d and e were obtained from para-2d and e with methacrylic acid chloride (45%, Scheme 2). The formation of 5 (6%), obviously via a [2+4]addition between the acrylate double bond in 4d as dienophile and a molecule of methacrylic acid chloride as the heterodiene, acts as a warning when treating methacrylate monomers with methacrylic acid chloride.The copolymerization of methyl methacrylate with 4d and e were easily accomplished with azoisobutyronitrile as initiator. The free radical polymerization of the analogous derivatives of naphthacenequinone was not possible.3 The properties of the solid copolymers resemble closely that of polymethyl methacrylate. It dissolves well e.g. in dichloromethane. Solid thin layers showed the same photochromism as solutions of 4d and e. The synthesis of the 1-amino-4-alkoxy-9,10-anthraquinone 6 was realized by nucleophilic substitution of the chlorine in 1 by deprotonated triethylene glycol monomethyl ether.Compound 7 was obtained by a nucleophilic substitution of the oligoether group in 6 with propanolate as nucleophile; 6 and 7 gave no photoisomerization at irradiation l 310–460 nm. The quantum efficiencies for the isomerization para- 2dhana-2d has been determined to be f=1.73Å10µ2 (l=436 nm), and for the isomerization ana-2dhpara-2d f=1.63Å10µ3 (l=577 nm), respectively.The absorption cross sections s were measured to be spara-2d=1.10Å10µ17 cm2 [log e (447 nm)=3.82], and sana-2d=8.13Å10µ18 cm2 [log e (580 nm)=3.69]. Considering the simple synthetic access and the thermal stability of the photoisomers the described photochromic *To receive any correspondence (e-mail: p.boldt@tu-bs.de). †Part 15. P. Boldt and S. Zippel, Synthesis, 1997, 173. Scheme Scheme 2O O R NH2 6 R = [O(CH2)2]3OMe 7 R = O[CH2]2Me J. CHEM.RESEARCH (S), 1997 387 polymeric materials may be of use in holographical storage systems or other technical imaging processes.11 Techniques used: IR, UV–VIS, 1H NMR, 13C NMR, MS. References: 16 Schemes: 4 Fig. 1: Absorption spectrum of para-2d in toluene and the spectral change on irradiation at 436 nm Fig. 2: Absorption spectrum of ana-2d in toluene and the spectral change on irradiation at 577 nm Received, 7th March 1997; Accepted, 22nd July 1997 Paper E/7/01624G References cited in this synopsis 1 Reviews: (a) B. L. Feringa, W. F. Jager and B. de Lange, Tetrahedron, 1993, 49, 8267; (b) H. Menzel, Nachr. Chem. Tech. Lab., 1991, 39, 636; (c) Photochromism. Molecules and Systems, ed. H. D�urr and H. Bouas-Laurent, Elsevier, Amsterdam, 1990; (d) C. B. McArdle, Pure Appl. Chem., 1996, 68, 1389. 2 A. I. Ponyaev, E. R. Zakhs, D. Klemm and E. Klemm, in Organic Photochromes, ed. A. V. El’tsov, Plenum Publishing Corporation, New York, 1990, 1st edn., ch. 4, p. 210 ff. 3 F. Buchholtz, A. Zelichenok and V. Krongauz, Macromolecules, 1993, 26, 906. 5 Y. E. Gerasimenko, N. T. Poteleshchenko and V. V. Romanov, J. Org. Chem. USSR, 1978, 14, 2199. 6 Badische Anilin- and Soda-Fabrik, Ludwigshaven/Rh, D. R. P. 199 758, Juli 23, 1907. 11 See for example, Ciba-Geigy AG, Basel, invs.: W. Fischer, E. Fischer, E. Minder, M. Hofmann, J. Finter and H. Spahni, A1 910 724, EP application 438 37

ISSN:0308-2342    

DOI:10.1039/a701624g

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

ArCH2NH2 + Ph—CH C(CN)(C6H4NO2) PhCH NHCH2Ar CH(CN)(C6H4NO2) (1) Ph CH C CN Ar Ph CH C CN Ar + H2NR N+H2R – k1 k–1 1 1 Ph CH CH CN Ar NHR k3 [H2NR] R = CH2Ph, Ar = p-NO2C6H4 388 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 388–389 J. Chem. Research (M), 1997, 2358–2377 Correlation Analysis of Reactivity in the Addition of Substituted Benzylamines to a-Cyano-4-nitrostilbene Bindu Varghese, Deepa Suri, Seema Kothari and Kalyan K. Banerji* Department of Chemistry, J.N.V.University, Jodhpur 342 005, India The addition of benzylamine to a-cyano-4-nitrostilbene involves the formation of a zwitterionic species in an equilibrium and its subsequent decomposition catalysed by a second molecule of the amine. Synthetic and mechanistic studies of the additions to activated carbon–carbon double bonds are of immense importance. However, not many reports are available about the addition of neutral nucleophiles to activated double bonds.5–10 In this paper, we report the addition of a number of monosubstituted benzylamines to a-cyano-4-nitrostilbene (CNS).Attempts have been made to correlate the rate and structure in this reaction. CNS was prepared by the reported method.11 The reaction was studied under pseudo-first-order conditions by keeping a large excess (Å10 or greater) of benzylamine over CNS. The solvent was acetonitrile. The reaction was followed spectrophotometrically by monitoring the decrease in [CNS] at 340 nm for ca. 80% reaction. The pseudo-first-order rate constant, kobs, was evaluated from the linear (r2a0.998) plots of log [CNS] vs. time. Addition of benzylamine to CNS leads to the formation of 1-benzylamino-2-cyano-1-phenyl-2-(4-nitrophenyl)ethane, PhCH(PhCH2NH)CH(CN)(C6H4NO2), as ascertained by its 1H NMR spectrum. The overall reaction may be represented as eqn. (1). The reaction is first order with respect to CNS. Values of kobs increase with an increase in the concentration of benzylamine.The apparent order in [amine], as determined by a log–log plot is greater than unity (slope=1.88�0.01; r2=0.9998). It was observed that a plot of kobs/[amine] vs. [amine] is curvilinear with a negligible intercept. The absence of an intercept indicates that an uncatalysed pathway is not important in this reaction. Therefore, a mechanism, involving formation of the zwitterionic intermediate in the pre-equilibrium with its subsequent decompsition into the product, via a proton transfer, catalysed by a second molecule of the amine, is proposed (Scheme 1).The addition of deuterated benzylamine to CNS exhibited a substantial primary kinetic isotope effect, kH/kD=5.49 at 293 K. This confirmed the cleavage of an N·H bond in the rate-determining step and supports the proposed mechanism. Application of the steady-state treatment to this mechanism (Scheme 1) gives the rate law (3). kobs [amine] =k2= k1k3[amine] kµ1+k3[amine] (3) A plot of (k2)µ1 against [amine]µ1 is a straight line (r2=0.9990).The inverse of the intercept gives the rate constant, k1, of the nucleophilic attack by amine on CNS. The kinetics of the addition of benzylamine and 27 mono-substituted benzylamines to CNS were studied. The kinetics were similar in all cases. The rate constants, k1, at different temperatures were evaluated. The activation parameters were also calculated. The rate constants for addition of meta- and para-substituted benzylamines do not show any significant correlation with the pKa values of the amine or the Hammett s values.*To receive any correspondence. Scheme 1 Table 3 Rate constants, k1, at different temperatures for the addition of substituted benzylamines to CNSa k1/mol dmµ3 sµ1 k1/mol dmµ3 sµ1 Subst. 293 K 303 K 313 K 323 K Subst. 293 K 303 K 313 K 323 K Hp -Me p-OMe p-F p-Cl p-NO2 p-CF3 p-CO2Me p-Br p-HNAc o-Me o-OMe o-F o-Cl 3.51 5.65 9.20 3.15 2.18 0.32 0.76 0.94 2.13 5.31 2.69 3.65 1.43 0.83 5.54 8.65 13.7 5.04 3.56 0.61 1.33 1.62 3.51 8.22 4.31 5.90 2.45 1.46 8.82 13.7 19.7 7.95 5.78 1.11 2.31 2.83 5.80 12.6 6.98 9.39 4.15 2.57 13.8 20.7 29.6 12.7 9.43 2.00 3.98 4.79 9.28 19.6 10.9 14.5 6.80 4.36 o-Br o-NO2 o-CF3 o-CO2Me o-NHAc m-Me m-OMe m-F m-Cl m-I m-NO2 m-CF3 m-CO2Me m-NH2 0.72 0.20 0.25 0.51 1.58 4.61 3.56 1.33 1.22 1.40 0.31 0.78 1.01 6.89 1.27 0.38 0.47 0.91 2.66 6.69 5.42 2.23 2.07 2.36 0.61 1.43 1.79 9.76 2.25 0.73 0.91 1.69 4.49 10.9 8.83 3.89 3.61 4.03 1.17 2.53 3.12 15.2 3.85 1.37 1.67 2.95 7.33 17.0 14.0 6.50 6.03 6.75 2.06 4.31 5.22 23.3 aAbbreviated version of the corresponding table contained in the full text.J.CHEM. RESEARCH (S), 1997 389 Similarly the rate constants for the ortho- compounds did not correlate well with s0 values.21 The correlation of the rate constants for meta and para compounds in terms of Taft’s dual substituent parameter equation22 also was poor. The rate constants, k1, were therefore analysed in terms of Charton’s23 LDR eqn.(8) log k1=Ls1+Dsd+Rse+h (8) Here, s is a localized (field and/or inductive) effect parameter, sd is the intrinsic delocalized (resonance) electrical effect parameter when active-site electronic demand is minimal and se represents the sensitivity of the substituent to change in electronic demand by the active site. The latter two substituent parameters are related by eqn. (9), sD=nse+sd (9) where n, represents the electronic demand of the reaction site which is given by n=R/D, and sD represents the delocalized electrical parameter of the diparametric LD equation.For ortho-substituted compounds, it is necessary to account for the possibility of steric effects. The LDR equation is, therefore, modified to LDRS eqn. (10), where V is the well known Charton’s steric parameter based on Van der Waals radii.24 log k1=Ls1+Dsd+Rse+SV+h (10) The rates of addition of the ortho-, meta- and para-substituted benzylamines showed excellent correlations with LDR/ LDRS equations with all the four regression coefficients, L, D, R and S, being negative.The negative values of L, D and R indicate an electron-deficient reaction centre in the transition state of the reaction. The positive value of n adds a negative increment to sd [eqn. (9)], increasing the donor effect of the substituent where sd is negative and decreasing the acceptor effect where sd is positive. The substituent is, therefore, better able to stabilize a cationic reaction site.This also supports the presence of an electron-deficient centre in the transition state of the rate-determining step. The magnitude of n points to a relatively small electronic demand of the reaction centre. The negative value of S indicates that the reaction is subject to steric hindrance by the ortho substituent. This may be due to steric hindrance of the ortho substituent to the approach of amines to CNS. Comparison of the L and D values for the substituted benzylamines showed that the addition of para-substituted benzylamines is more susceptible to delocalization rather than localized effects.However, the addition of ortho- and meta-substituted compounds exhibits a greater dependence on the field effect. Thanks are due to the University Grants Commission (India) for financial support. Techniques used: 1H NMR, spectrophotometry, correlation analysis References: 25 Figure: 1 Table 1: Rate constants for the addition of benzylamine to CNS at 293 K Table 2: Rate constants, k1, at different temperatures and activation parameters for the addition of substituted benzylamines to CNS Table 3: Correlation analysis of the rates of addition of meta- and para-substituted benzylamines to CNS with Taft’s dual substituentparameters at 298 K Table 4: Correlation analysis of the rates of addition of substituted benzylamines to CNS with LDR/LDRS equations at different temperatures Received, 24th December 1996; Accepted, 25th July 1997 Paper E/7/08621G References cited in this synopsis 5 C.F. Bernasconi, R. A. Rentfrow and P. R. Tia, J. Am. Chem. Soc., 1986, 108, 4541. 6 C. F. Bernasconi and M. Panda, J. Org. Chem., 1987, 52, 3042. 7 R. Kada, V. Knoppova, J. Kovac and I. Malenakova, Collect. Czech. Chem. Commun., 1984, 49, 2496. 8 A. F. Popov, I. F. Perepichka anL. I. Kostenko, J. Chem. Soc., Perkin Trans. 2, 1989, 395. 9 C. F. Bernasconi and R. B. Killion, J. Org. Chem., 1989, 54, 2878. 10 A. Shunmugasundaram, L. Thanuligam and R. Murugesan, Indian J. Chem. Sect. A, 1991, 30, 609. 11 A. Schonne, E. Braye and A. Bruylants, Bull. Soc. Chim. Belg., 1953, 62, 155. 21 M. T. Tribble and J. G. Traynham, J. Am. Chem. Soc., 1969, 91, 379. 22 S. Dayal, S. Ehrenson and R. W. Taft, J. Am. Chem. Soc., 1972, 94, 9113. 23 M. Charton and B. Charton, Bull. Soc. Chim. Fr., 1988, 199 and references cited therein. 24 M. Charton, J. Org. Chem., 1975, 40, 407.

ISSN:0308-2342    

DOI:10.1039/a708621g

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Me O Me HO 1 Me O 2 Me KOH–MeOH heat O Me Me O Me Me 3 O Me Me H H R heat 4 R = H CH2Br CH2Br 6 Me Me 5 NBS–(PhCO)2O2 heat O O 1 2 3 1 2 3 7 O O 8 FVP, 800 °C 390 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 390–391 J. Chem. Research (M), 1997, 2417–2433 A Short Synthesis of 1,4-Dimethyltriphenylene M. John Plater,* Derek M. Schmidt and R. Alan Howie Department of Chemistry, Aberdeen University, Meston Walk, Aberdeen AB24 3UE, UK The title compound was prepared by the interception of 1,3-dimethylcyclopenta[l ]phenanthren-2-one 2 with norbornadiene to give the Diels–Alder adduct 4 followed by flash vacuum pyrolysis.In a preceding paper1 we described our interest in cyclopentafused polycyclic fragments related to the Buckminsterfullerene surface and reported the synthesis and X-ray crystal structure of (1R,11bR)-11b-hydroxy-1,3-dimethyl-2,11b-dihydro- 1H-cyclopenta[l ]phenanthren-2-one 1 which was prepared by the base catalysed condensation of diethyl ketone with phenanthrenequinone.2,3 Although direct methods of dehydration reported previously have been unsuccessful, treatment with KOH in refluxing MeOH eliminates water to generate 1,3-dimethylcyclopenta[l ]phenanthren-2-one 2.This spontaneously forms the dimer 3 which precipitates as a colourless solid. The dimer 3 has been reported previously2,3 and is unusual because there are only two signals for methyl groups in the 1H NMR spectrum. This was rationalised as arising from a degenerate [3,3] Cope rearrangement which occurs rapidly on an NMR timescale at room temperature in solution.The rearrangement interconverts two pairs of methyl groups, so two averaged signals are observed. An energy barrier of 11.4 kcal molµ1 was calculated for the interconversion from low temperature NMR data. The arrangement is illustrated for the cyclopentadienone sub-structures 7 and 8. We expected that dimer 3 might therefore have rather long carbon–carbon bonds holding it together and so performed an X-ray single crystal structure analysis (Fig. 1).4 This shows the expected endo stereochemistry of the [4+2] Diels–Alder dimer. The bonds holding the dimer together [C(15)·C(34) and C(16)·C(32)], of length 1.602(7) and 1.649(6) Å respectively, are indeed long and weak. A typical covalent C·C bond is 1.54 Å long. To date the longest C·C bonds which have been reliably determined by X-ray crystallography are 1.720(4) and 1.710(5) Å.5,6 The distance between the terminal carbons of the alkenes which bond together during the Cope rearrangement7 is 3.178(6) Å.Heating the dimer in norbornadiene gave the cycloadduct 4. The endo stereochemistry was confirmed by the upfield shielding of the bridgehead methylene proton (R=H) which resonates at µ0.46 ppm. Flash vacuum pyrolysis (FVP) through an unpacked quartz tube at 800 °C gave 1,4-dimethyltriphenylene8 via initial decarbonylation followed by a retro Diels–Alder reaction extruding cyclopentadiene.Free radical bromination gave the precursor 6. Ring closure attempts to give a fullerene fragment with two five-membered rings were however unsuccessful. Pyrolysis of precursor 6 gave a complex reaction mixture from which none of the desired cyclised product was isolated. This contrasts with the successful FVP ring closure of two bromomethyl groups on route to sumanene.9 Presumably precursor 6 may eliminate bromine to give a paraquinonedimethane which may not be reactive enough to cyclise.Alternative approaches to cyclopenta-fused polycyclic fragments of the Buckminsterfullerene surface are in progress. Crystal Data for 2.·C38H28O2, Mr=516.6, F(000)= 2176, orthorhombic, a=10.931(3), b=34.917(17), c= 13.754(8) Å, V=5250(4) Å3, space group Pbca, Z=8, *To receive any correspondence. Fig. 1 Perspective view of the dimer 3 showing the atom numbering scheme. Non-hydrogen atoms are shown as 40% probability ellipsoids and hydrogen atoms as spheres of arbitrary radiusJ.CHEM. RESEARCH (S), 1997 391 Dx=1.307 g cm3, m(MoKa)=0.079 mmµ1. The experimental data were collected at 298 K on a Nicolet P3 diffractometer with MoKa radiation (l=0.71069 Å) and refined using Nicolet P3 software. The structure was solved by direct methods and refined by full matrix least squares on F2. Final R indices [Ia2s(I)] R1=0.0756, wR2=0.1252, for all data R1=0.2169 and wR2=0.1933. The estimated standard deviations for the geometrical parameters involving non hydrogen atoms lie within the following ranges: bond lengths 0.004–0.007 Å; bond angles 0.3–0.6°.Techniques used: IR, 1H and 13C NMR, mass spectrometry, X-ray crystallography References: 15 Schemes: 1 Table 1: Crystal data and structure refinement 3 Table 2: Atomic coordinates and Ueq values for 3 Tables 3 and 4: Interatomic distances and angles, and selected dihedral angles Table 5: Anisotropic displacement parameters for 3 Table 6: Hydrogen coordinates and isotropic displacement parameters for 3 Received, 20th June 1997; Accepted, 30th July 1997 Paper E/7/04351A References 1 M.J. Plater, D. M. Schmidt and R. A. Howie, J. Chem. Res., 1997, (S) 140; (M) 0977–0982. 2 D. W. Jones, J. Chem. Soc., Perkin Trans. 1, 1988, 980; D. W. Jones, J. Chem. Soc., Chem. Commun., 1975, 199. 3 B. Fuchs, M. Pasternak and G. Sharf, J. Chem. Soc., Chem. Commum., 1976, 53. 4 For crystal structures of [4+2] cyclopentadienone dimers see J. Beauhaire, A. Chiaroni, J. L. Fourrey and C. Riche, Tetrahedron Lett., 1983, 24, 4417; J. M. M. Smitts, V Parthasarathi, P. T. Beurskens, A. J. H. Klunder and J. H. M. Lange, J. Crystallogr. Spectrosc. Res., 1988, 18, 791; F. Toda, K. Tanaka, D. Marks and I. Goldberg, J. Org. Chem., 1991, 56, 7332. 5 F. Toda, K. Tanaka, Z. Stein and I. Goldberg, Acta Crystallogr., Sect. C, 1996, 52, 177. 6 G. Kaupp and J. Boy, Angew. Chem., Int. Ed. Engl., 1977, 36, 48. 7 For a review on Cope rearrangements see J. March, Advanced Organic Chemistry, Wiley, New York, 4th edn, 1992, p. 1130. 8 J. Fieser, J. Am. Chem. Soc., 1939, 61, 2958; B. Fuchs and G. Scharf, J. Org. Chem., 1981, 46, 5395. 9 G. Mehta, S. R. Shah and K. Ravikumar, J. Chem. Soc., Chem. Commun., 1993, 1006.

ISSN:0308-2342    

DOI:10.1039/a704351a

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N N HN CF3 NH2 1 ArCH C(CN)2 2a–g N N N CF3 NH2 CN Ar CN 3 HN N N CF3 NH Ar CN NC 5 N NH N N Ar CN NH2 CF3 N NH N N NH2 CN Ar CF3 4a–g 6a–g NH N N N Ar CF3 8a–g CH2(CN)2 1 ArCHO 7a–g N NH N N NH2 CO2Et Ar CF3 10a–e N NH N N O CN Ar CF3 11a–e CN CH2CO2Et ArCH C(CN)CO2Et Ar Ph C6H4Me- p C6H4F- p C6H4NO2- p C6H4OMe- p S 2-10 a b c d e f g C6H4Cl- p 9a–e 392 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 392–393 J. Chem. Research (M), 1997, 2378–2394 Reactions with 3-Amino-5-trifluoromethyl-1,2,4-triazole: a Simple Route to Fluorinated Poly-substituted Triazolo[1,5-a]pyrimidine and Triazolo[5,1-c]triazine Derivatives Hussein F.Zohdi* Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt 3-Amino-5-trifluoromethyl-1,2,4-triazole has been utilized for the syntheses of poly-substituted 2-trifluoromethyl- [1,2,4]triazolo[1,5-a]pyrimidine derivatives, via its reactions with acrylonitrile derivatives and various 1,3-dicarbonyl compounds, and of trifluoromethyl[1,2,4]triazolo[5,1-c]triazine derivatives, via its diazotization and coupling with active methylene reagents.Fluorine-containing heterocyclic compounds have received considerable interest owing to their potent pharmacological activity.1,2 In continuation of our interest in the synthesis of azoles and their fused derivatives bearing a trifluoromethyl group,6–8 we report herein the utility of 3-amino-5-trifluoromethyl- 1,2,4-triazole9 for the synthesis of several new polysubstituted 2-trifluoromethyl[1,2,4]triazolo[1,5-a]pyrimidine and 7-trifluoromethyl[1,2,4]triazolo[5,1-c][1,2,4]triazine derivatives required for a medicinal chemistry programme.The reaction of 3-amino-5-trifluoromethyl-1,2,4-triazole (1) with various b-aryl-a-cyanoacrylonitrile derivatives 2a–g afforded in each case a single product, as evidenced by TLC. Based on analytical data, two isomeric structures are possible, 5-amino-7-aryl-6-cyano-4,7-dihydro-2-trifluoromethyl- [1,2,4]triazolo[1,5-a]pyrimidine 4 or its regioisomer 7-amino- 5 - a r y l - 6 - c y a n o - 4 , 5 - d i h y d r o - 2 - t r i f l u o r o m e t h y l [ 1 , 2 , 4 ] t r i a z o l o- [1,5-a]pyrimidine 6 (Scheme 1).Spectrosocpic data could not distinguish between these two, and therefore further evidence for the correct structure was sought by approaching the product through another route. Thus, treatment of the Schiff’s bases 8a–g with malononitrile afforded products identical in all respects with those obtained from the reaction of 1 with 2a–g.The formation of compounds 6a–g is, therefore, assumed to proceed via initial attack of the exocyclic amino group of 1 on the activated double bond of 2 to form the non-isolable Michael adduct 5, which alternatively can be formed via the addition of the active methylene of malononitrile to the double bond of the Schiff’s base 8. This Michael adduct then undergoes intramolecular cyclization to afford compounds 6a–g (Scheme 1).Compound 1 reacted with ethyl b-aryl-a-cyanoacrylate derivatives 9a–e to yield in each case a single product which may be formulated as ethyl 7-amino-5-aryl-4,5-dihydro-2-trif l u o r o m e t h y l [ 1 , 2 , 4 ] t r i a z o l o [ 1 , 5 - a] p y r i m i d i n e - 6 - c a r b o x y l a t e 10 or 5-aryl-6-cyano-4,5,6,7-tetrahydro-2-trifluoromethyl- [1,2,4]triazolo[1,5-a]pyrimidin-7-one derivatives 11 (Scheme 1). Structure 11 was readily ruled out for the reaction products on the basis of analytical and spectroscopic data, and support for structure 10 was provided by independent syntheses of compounds 10a–e from the reaction of the appropriate Schiff’s base 8a–e with ethyl cyanoacetate.It is worth noting that the reaction of ethyl cyanoacetate with each of 8f,g gave ethyl b-(p-methoxyphenyl)-a-cyanoacrylate (9f) and ethyl b-thienyl-a-cyanoacrylate (9g), respectively, along with compound 1. The reaction of compound 1 with several b-diketones, b-keto esters and their a-substituted derivatives was carried out by heating either in acetic acid or, preferably, in toluene.*E-mail: ZOHDI@FRCU.EUN.EG Scheme 1N NH N N CF3 O R2 R1 N NH N N CF3 R1 R2 O 12 a b c d e R1 CF3 Me Me Me Me H H Cl N N Ph N N C6 H4Me- p R2 12a–e 13 R1COCH(R2)CO2Et 1 N N N N CF3 Me X Me N N N N CF3 R2 R1 a X = H b X = Cl 15 14a–c R1 R2 a Me Ph b CF3 Me c CF3 S 14 MeCOCH(X)COMe R1COCH2COR2 N NH N N CF3 O O N NH N N CF3 O N O 16 17a,b 1 N N N N N CF3 NH2 CO2Et N N N N N CF3 NH2 19 20 NCCH2CO2Et CH2(CN)2 NH Ar CH2(CO2Et)2 a Ar = C6H4NO2- p b Ar = C6H4Me- p ArN2 +Cl– CN HN N N CF3 N2 + 18 HONO p-NO2C6H4NHN C(CO2Et)2 J.CHEM. RESEARCH (S), 1997 393 Thus, the reaction of 1 with ethyl 4,4,4-trifluoroacetoacetate, ethyl acetoacetate, ethyl 2-chloroacetoacetate and ethyl 2-arylazoacetoacetate produced in each case in a single product, as evidenced by TLC. The reaction products can be represented as [1,2,4]triazolo[1,5-a]pyrimidin-7-one derivatives, 12a–e (Scheme 2), evidence for the assigned structures being provided by analytical and spectroscopic data.Although one may argue that the reaction of 1 with b-ketoesters may lead to the other possible regioisomer (the [1,2,4]triazolo[1,5-a]pyrimidin-5-one, 13) the regioselectivity of such reactions is well established.10,11 The reaction of compound 1 with benzoylacetone, 1,1,1-trifluoropentane-2,4-dione and thenoyltrifluoroacetone produced in each case a mixture of two regioisomers, as evidenced by TLC of the crude products.The major products, 14a–c (Scheme 2), were obtained in good yield after recrystallization. The assigned regiochemistry is in agreement with literature reports12–14 regarding the reactions of aminoazoles with asymmetric 1,3-diketones. Similarly, the reaction of compund 1 with acetylacetone and 3-chloroacetylacetone afforded 5,7-dimethyl-2-trifluoromethyl- [1,2,4]triazolo[1,5-a]pyrimidine and its 6-chloro derivative, 15a,b, respectively.Compound 1 reacted with diethyl malonate in refluxing toluene to produce 4,6-dihydro-5,7-dioxo-2-trifluoromethyl- [1,2,4]triazolo[1,5-a]pyrimidine (16). Compound 16 underwent electrophilic substitution upon coupling with arenediazonium chloride at the active methylene to afford the corresponding aryl hydrazone derivatives 17a,b. Compound 17a was alternatively prepared by heating compound 1 with diethyl p-nitrophenylazomalonate in toluene at reflux (Scheme 3).The reactions of 5-trifluoromethyl[1,2,4]triazole-3-diazonium sulfate (18) with ethyl cyanoacetate, and with malononitrile, in pyridine afforded ethyl 4-amino-7-trifluoromethyl[ 1,2,4]triazolo[5,1-c]triazine-3-carboxylate (19) and 4-amino-3-cyano-7-trifluoromethyl[1,2,4]triazolo[5,1-c][1,2,4]- triazine (20), respectively (Scheme 3). Techniques used: IR, 1H NMR, 13C NMR, mass spectrometry References: 15 Received, 17th February 1997; Accepted, 28th July 1997 Paper E/7/01093A References cited in this synopsis 1 J.W. Welch and S. Eswarakrishnan, in Fluorine in Bioorganic Chemistry, Wiley, New York, 1991. 2 R. Filler and S. M. Naqui, in Biomedical Aspects of Fluorine Chemistry, Elsevier Biomedical, Amsterdam, 1982, p. 1. 6 H. F. Zohdi, J. Chem. Res. (S), 1992, 82. 7 H. F. Zohdi, A. H. H. Elghandour, N. M. Rateb and M. M. M. Sallam, J. Chem. Res., 1992, (S) 396; (M) 3015. 8 H. F. Zohdi, H. Y. Afeefy and A. O. Abdelhamid, J. Chem. Res. (S), 1993, 76. 9 V. A. Lopyrev and T. N. Rakhmatulina, Zh. Obshch. Khim., 1983, 53, 1684 (Chem. Abstr., 1983, 99, 139865y). 10 G. Maury, in Special Topics in Heterocyclic Chemistry, ed. A. Weissberger and E. C. Taylor, Wiley–Interscience, New York, 1977, p. 196. 11 J. S. Bajwa and P. J. Sykes, J. Chem. Soc., Perkin Trans. 1, 1979, 3085. 12 R. Balicki, Polish J. Chem., 1981, 55, 1985. 13 A. Kreutzberger and L. Manfred, Arch. Pharm. (Weinheim), 1982, 315, 438. 14 W. A. Kleschick and J. Bordner, J. Heterocycl. Chem., 1989, 26, 1489. Scheme 2 Scheme 3

ISSN:0308-2342    

DOI:10.1039/a701093a

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

CHO NO2 MeNO2 NaOH, 0°C OMe NOH Cl H R N O Ar Ar¢ 2 Et3N 1a R = H b R = OMe AlCl3 + – O R* I OH Br I + R—Cl + R*—OH II II O O O O HO OH D-Mannitol acetone O O H O NalO4, H2O O O OH NaBH4 O O O H NaOH, PTC, 0 °C H 7 6 H anh.ZnCl2 propargyl bromide N H CO2H H N CO2CH2Ph CO2H H N CO2CH2Ph H OCO2Et O 8 9 N CO2CH2Ph H 10 OH N CO2CH2Ph H 11 O i ii iii iv 394 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 394–395 J. Chem. Research (M), 1997, 2459–2471 Intermolecular Diastereoselective Nitrile Oxide Addition with Propargylic Ethers Subramanian Baskaran,*a Chitra Baskarana and Girish K.Trivedib aFachbereich Chemie der Philipps-Universit�at, Marburg, D-35032, Germany bDepartment of Chemistry, Indian Institute of Technology, Powai, Mumbai 400 076, India Cycloaddition reactions of the nitrile oxide 2 are performed with simple and stereogenic propargylic ethers 3–5, 7 and 11 in moderately high yield and with considerable regioselectivity. Nitrones and nitrile oxides are amongst the most useful 1,3-dipoles in organic synthesis.Recently the topic has received renewed attention in view of the now widespread use of nitrile oxide–isoxazoline chemistry1 for the synthesis of natural products and analogues. The asymmetric 1,3-dipolar cycloaddition of a nitrone, diazomethane and a nitrile oxide using an optically active allyloxy unsaturated ester was recently reported by us.2 In continuation of our effort to utilise heterocyclic compounds as dipolarophiles in 1,3-dipolar cycloaddition reactions, we have investigated the cycloaddition of stereogenic propargylic ethers with the rac nitrile oxide 2.It has been established that3–5 allylic substrates have a strong influence in determining the p-facial selectivity and that notably high levels of diastereoselectivity are observed for cycloaddition to chiral allylic ethers and esters. Moreover it is interesting to note that intermolecular 1,3-dipolar cycloadditions between nitrile oxides and chiral propargylic ethers have been studied6 sporadically.Martin and Dupre9 have demonstrated the importance of congested nitrile oxides in the high degree of regioselectivity observed during their cycloaddition with substituted olefins, as the 5-substituted regiomer was selectively formed over the 4-substituted one. Hurd et al.10 in their studies on reactions of nitroolefins devised a method in which benzene reacts with b-nitrostyrene in the presence of anhydrous aluminium chloride to yield diphenylacetohydroximoyl chloride 1a in good yield.We have examined methods for the generation of nitrile oxides in which the stereogenic centre is in the nitrile oxide component,12 and investigated their cycloaddition with achiral and chiral alkynes. Hence, rac-1-(4-methoxyphenyl)- 1-phenylacetohydroximoyl chloride 1b, a hitherto unknown dipole precursor, was synthesised (Scheme 1). For the preparation of propargylic ethers, a retrosynthetic analysis (Scheme 2) shows that it can be constructed via two pathways.For achiral dipolarophiles we utilised strategy I and for chiral dipolarophiles we utilised strategy II. Thus compounds 4 and 5 were synthesised by coupling propargyl alcohol with rac-epichlorohydrin and benzyl chloride respectively. 13 The other two alkynes 7 and 11 were synthesised from D-mannitol and L-proline as illustrated in Schemes 4 and 5. In order to minimise the formation of furazan nitrile oxide (furoxan) dimers, the nitrile oxides were generated in situ from the corresponding oximes.The nitrile oxide generated at 0–5 °C by slow addition of Et3N to the nitrile oxide precursor 1b in dichloromethane was treated with 3–5, 7 and 11 in dichloromethane to yield mixtures of products. The resulting isoxazolines were readily separated in moderate yields by flash chromatography. Like other reports,6,14 1,3-dipolar cycloadditions of nitrile oxides 2 (Scheme 6) with the alkynes (3–5,7,11) were shown to be highly regioselective.The only regiomers detected by 1H-NMR being those with a terminal H at C-4, i.e., the sterically less hindered 5-substituted products. If it had been a 4-substituted ring, the olefinic proton signal should have appeared at around d 8, as it is flanked by both a heterocyclic *To receive any correspondence (e-mail: baskaran@ps1515. chemie.uni-marburg.de). Scheme 1 Scheme 2 Scheme 4 Scheme 5 Reagents and conditions: i, ClCOOCH2Ph, NaOH, PTC, 0 °C; ii, Et3N, ClCOOEt, THF, 0 °C; iii, NaBH4, H2O, room temp.; iv, propargyl bromide, NaOH, 0 °C, PTCOH 3 O N HO X 5 4 3 2 1 12 Ph 4-MeO-C6H4 Cl NOH 1b Et3N, CH2Cl2, 0 °C X = OMe H 1¢¢ O 4 O O O O N X H + RS SR 1b 13 O 5 O O N X 14 1b O O H O 7 O O H O 15 N O X 10 S 8 SS + SR 1b SS RR N O H CO2CH2Ph 11 N O N O X H P 11 9 6 4 1 + SR 1b SS 16 P = CO2CH2Ph 8 S N Ar H Ar¢ O S X H Ar Ar¢ N O + – + O O H H O H H O N Ar¢ H Ar O O O H 10 S 2 1 5 6 8 9 S 4 O N Ar H Ar¢ O O O H R 15a [ SS] 15b [ SR] O O H H H S N Ar¢ H Ar O R X H O O H H H S Ar¢ = p-OMeC6H4 X = OCH (No facial difference) 7 J.CHEM. RESEARCH (S), 1997 395 oxygen and a double bond. However, the appearance of ole- finic protons in the range d 6.02–6.09 indicates the formation of a 5-substituted isoxazoline ring. In the case of 4, 7 and 11 the cycloaddition provided inseparable mixtures of two diastereomers (from the OMe 1H NMR signals) in the ratio of 1:1.The formation of two diastereomers was expected because of the pre-existing chirality of dipolarophiles. The preferred formation15,16 of the adducts can be explained by the fact that the dipolarophile reacts by its preferred conformation with the rac-dipole (Fig. 1). The p-facial selectivity observed for the reaction of nitrile oxides with the dipolarophiles can be rationalised for the adduct 15 by adapting the ‘inside alkoxy group hypothesis’ proposed by Houk et al.3 for the cycloaddition of chiral allyl ethers.The preferred formation of the adduct from an alkyne is consistent15,16 with product formation via the transition state which locates the oxygen substituent in the ‘inside’ position, the hydrogen ‘outside’ and the CH2O moiety anti (Fig. 1). The two products (diastereomers) were formed by kinetic resolution of the nitrile oxide while reacting with the dipolarophile. For the compounds 15 and 16, the proton signals for the two allylic methylene protons are seen at d 4.61 and 4.50 and the vinylic protons are seen at d 6.10 and 6.03 respectively.This unequivocally confirms the formation of the 5-substituted regiomer. The 1H NMR spectra of each compound (except for 12 and 14) showed that only two diastereomers were obtained, which could be in SS and SR configuration (Fig. 1). Since the asymmetric centres in the above cases (15 and 16) are remote from the reaction centres, the absolute stereochemistry of the adducts could not be determined.All the assignments were corroborated by 13C NMR and 2D (1H-1H) COSY experiments. In conclusion, 1,3-dipolar cycloadditions on enantiomericlaly pure propargylic ethers with rac nitrile oxides occurred with moderate conversion as well as with complete regioselectivity. 5 In each case the effect12 can be attributed to the greater distance between the pre-existing and newly formed stereocentres (because of the diasteromeric nature of the products).Techniques used: IR, 1H and 13C NMR, 2D (1H-1H) COSY References: 16 Schemes: 6 Figures: 2 Received, 8th May 1997; Accepted, 12th August 1997 Paper E/7/03166A References cited in this synopsis 1 C. J. Easton, C. M. M. Hughes, G. P. Savage and G. W. Simpson, Adv. Heterocycl. Chem., 1994, 60, 261 and references cited therein. 2 S. Hariharan and G. K. Trivedi, Indian J. Chem., 1988, 27, 994; J. Vasu, P. J. Nadkarni, G. K. Trivedi and A. Steigel, Magn. Reson. Chem., 1991, 29, 645; S.Baskaran and G. K. Trivedi, J. Chem. Res., 1995, (S) 308; (M) 1853; 1996, (S) 542; S. Baskaran, J. Vasu, K. K. Ram Prasad, G. K. Trivedi and J. Chandrasekhar, Tetrahedron, 1996, 52, 4515; S. Baskaran, C. Baskaran, P. J. Nadkarni, G. K. Trivedi and J. Chandrasekhar, Tetrahedron, 1997, 53, 7057. 3 K. N. Houk, S. R. Moses, Y. D. W N. G. Rondan, J. Vager, R. Schohe and F. R. Fronczek, J. Am. Chem. Soc., 1984, 106, 3880. 4 A. P. Kozilkowski and A. K. Ghosh, J. Org. Chem., 1984, 49, 2762. 5 J. Blad, J. C. Carretero and E. Dominguez, Tetrahedron: Asymmetry, 1995, 1035 and references cited therein. 6 A. Padwa, U. Chiacchio, D. C. Dean, A. M. Schoffstall, A. Hassner and K. S. K. Murthy, Tetrahedron Lett., 1988, 29, 4169. 9 S. F. Matin and B. Dupre, Tetrahedron Lett., 1983, 24, 337. 10 C. D. Hurd, M. E. Nilson and D. M. Wiccholm, J. Am. Chem. Soc., 1950, 72, 4697. 12 A. J. Blake, E. C. Boyd, R. O. Gould and R. M. Paton, J. Chem. Soc., Perkin Trans. 1, 1994, 2841. 13 G. Mouzin, H. Cousse, J. P. Rieu and A. Duflos, Synthesis, 1983, 117. 14 For intra-cycloaddition see K. M. Short and K. B. Ziegler, Tetrahedron Let., 1993, 34, 75. 15 E. C. Boyd and R. M. Paton, Tetrahedron Lett., 1993, 34, 3169. 16 M. Mancera, I. Roffe and J. A. Galbis, Tetrahedron, 1995, 51, 6349. Scheme 6 The numbering of atoms deviates from the IUPAC rules, which are, however, obeyed in naming the compounds (see Experimental section) Fig. 1

ISSN:0308-2342    

DOI:10.1039/a703166a

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N N OMe OMe H N N OMe OMe H CO2Et H N N OMe OMe H N OMe OMe H CO2Et H 1a 1 3 4 5 6 7 8 9 10 11 2a 1 3 4 5 9 8 7 6 10 11 2 3a 3 1 4 5 6 7 8 9 10 4 R1 = R2 = H 5 R1 = H; R2 = CHO 7c R1 = CHO; R2 = H 2 R2 R1 OMe OMe Br HN COMe CN CN OMe OMe N COMe CN OMe MeO N H CN MeO MeO N H CN OMe OMe N H O C O Me 11c 12 13c Cu+ 15c 14c KOH–ethanol–H2O Pd(OAc)2 16 + OMe OMe NH Tos Br OMe OMe N Tos OMe OMe NH Me OMe OMe N H Br H OMe OMe N H OMe OMe N H Br H Br + 20 Cu 4 hn 21 8% 10% Pyridinium hydrobromide perbromide in [2H5]pyridine Pyridinium hydrobromide perbromide 27 HBr CD2Cl2, 4 days + NOE 398 J.CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 398–399 J. Chem. Research (M), 1997, 2501–2532 Antitumour Heterocycles. Part 16.1 The Synthesis of 7,10-Dimethoxyellipticine and its Pyrrolo[2,3-f]carbazole and Pyrrolo[3,2-f] Analogues Pryanthi Dharmasena,a Ana M. F. Oliveira-Campos,b Maria J. R. P. Queiroz,b M. Manuela M. Raposo,b Patrick V. R. Shannon*a and Christine M.Webba aDepartment of Chemistry, University of Wales, Cardiff, P.O. Box 912, Cardiff, UK bDepartment of Chemistry, University of Minho, Campus de Gualtar, 4700 Braga, Portugal The final examples in our ellipticine/pyrrolocarbazole synthesis programme are 7,10-dimethoxyellipticine 1a and the corresponding pyrrolocarbazoles 2a and 3a which have been synthesised from 4,6-dimethoxyindole. This paper describes an efficient synthesis of the novel 7,10-dimethoxyellipticine 1a and of the pyrrolocarbazole analogues 2a and 3a.Earlier work3 had shown that formylation of the carbazole 4 gave, predictably, the aldehyde 5 but experience suggested that its isomer 7c would prove a successful precursor to the new ellipticine 1a. Following the use of a carbazole nitrile in our synthesis of 8,10-dimethoxyellipticine,4 Goldberg6 coupling of the nitrile 12 with the bromide 11c gave the amide 13c (70%) which on alkaline hydrolysis afforded the diphenylamine 14c (71%).Palladium acetate oxidation of the latter, however, gave only a very poor yield of the desired cyanocarbazole 15c, together with a major by-product 16 (ca. 9%) (Scheme 1) and other acetoxylated products. The carbazole 4, prepared either as previously3 or by the route shown in Scheme 2, was brominated with pyridinium hydrobromide perbromide in dichloromethane to give almost exclusively the required 6-bromo derivative 21. In order to investigate the possibility of a rearrangement from an initially formed 3-bromo intermediate 27 (Scheme 4) we first carried out the bromination in [2H5]pyridine with step-wise addition of an excess of brominating agent, and 1H NMR analysis of the reaction mixture.Both the bromides 27 and 21, which were formed simultaneously, were identified from their 1H NMR spectra in the ratio 2:1 as intermediates to the 3,6-dibromide 28 (Scheme 5), these being the only compounds observed. Chromatography afforded pure samples of the carbazoles 21, 27 and 28.When the reaction was repeated in dichloro[2H2]methane (the synthetic intermediate was prepared in dichloromethane), the predominant intermediate to the dibromocarbazole 28 was the bromocarbazole 21 with only a minute trace of the 3-bromocarbazole 27. When a 1:1 mixture of carbazoles 4 and 27 was kept in dichloro[2H2]- methane in the presence of an excess of HBr, no change was evident during the first 5 h. However, on standing for 4 days the 3-bromocarbazole 27 had completely rearranged to the 5-bromo isomer 21.This rearrangement was much too slow to implicate the bromo derivative 27 as a significant intermediate in the rapid bromination of carbazole 4 to 21 in dichloromethane. We conclude that bromination of carbazole 4 to 21 is rapid and direct in dichloromethane in contrast to the reaction in pyridine in which the predominant monobromocarbazole is 27; presumably rearrangement is precluded by the absence of free HBr.Treatment of the bromide 21 with copper(I) cyanide in refluxing dimethylformamide (cf. ref. 7) gave the carbazole nitrile 22 (52%) instead of the 6-cyanocarbazole. This solid (mp 289–291 °C) was clearly in the conformation with the two carbazole systems in orthogonal planes; two OMe singlets, the 4- and 1p-signals, were at abnormally high field and the 8p-methyl singlet, similarly, was at d 1.88. The bromo- *To receive any correspondence. Scheme 1 Scheme 2 and 4OMe OMe N H OMe OMe N H Br OMe OMe N H Br Br OMe OMe N H Br 4 Pyridinium hydrobromide perbromide [2H5]pyridine 27 28 21 + + CN OMe OMe N CN OMe OMe N Br OMe OMe N CHO OMe OMe N OMe OMe N OMe OMe N Y X EtO OEt H OMe OMe N NTos H 23 X–Y = CH N 24 X–Y = CH2 NH 25 X–Y = CH2 NTos OMe OMe N N H H H H H 22 1¢ 2 4 6 8¢ + 21 7c 4 26 1a OMe OMe N H H2C O OAc N H CO2Et OMe OMe N H CO2Et OMe OMe N H CO2Et H N H H H Me N H N H CO2Et H OMe EtO2C O C H H H OMe N H OMe OMe O EtO2C EtO2C O N H N H OMe EtO2C O C H H H OMe N CO2 Et H N N H OMe EtO2C O C H H H OMe C CO2Et H H N O 29 + K10 clay 2a (9%) 14% 4% 2% 14% 4% 10% 3a (14%) + 30 (16%) 10% 0.7% 7% 12.5% 32 (0.5%) + 31 (16%) 7% 1.5% 10% 1.5% 0.7% 7 4 3 10 33 (5%) 12.5% 0.7% 7 H H 2.6% 2.6% + J. CHEM.RESEARCH (S), 1997 399 carbazole 21 was, however, converted directly into the aldehyde 7c (74%) with tert-butyllithium and dimethylformamide (cf. ref. 12). The aldehyde was condensed with aminoacetaldehyde diethyl acetal to the Schiff’s base 23 (97%) which was converted into the amine 24 (94%) and the sulfonamide 25 (37%) before cyclisation in hydrochloric acid–dimethyl sulfoxide to give a mixture of the N-tosyldihydroellipticine 26 (27.6%) and ellipticine 1c (63%) (Scheme 3).Chromatography and crystallisation gave the ellipticine 1c (mp 235–237 °C). Considerable losses of the ellipticine occurred on chromatography. Condensation of 4,7-dimethoxyindole with the pyrrole 29 in the presence of K-10 montmorillonite clay was expected to give a complex range of products. After extensive chromatography and fractional crystallisation, pure samples of the expected pyrrolocarbazoles 3a and 2a were isolated.The structures of these isomers and the by-products 30, 31, 32 and 33 (Scheme 6) followed unambiguously from their spectroscopic properties. Techniques used: 1H-NMR, mass spectrometry References: 13 Schemes: 6 Received, 1st July 1997; Accepted, 12th August 1997 Paper E/7/04615D References cited in this synopsis 1 Part 15, L. Chunchatprasert, W. Cocker and P. V. R. Shannon, J. Chem. Res., 1997, (S) 2; (M) 0101. 3 R. J. Hall, P. Dharmasena, J. Marchant, A. M.-F. Oliveira- Campos, M. J. R. P. Queiroz, M. M. Raposo and P. V. R. Shannon, J. Chem. Soc., Perkin Trans. 1, 1993, 1879. 4 L. Chunchatprasert, P. Dharmasena, A. M. F. Oliveira-Campos, M. J. R. P. Queiroz, M. M. M. Raposo and P. V. R. Shannon, J. Chem. Res., 1996, (S) 84; (M) 630. 6 (a) P. E. Weston and H. Adkins, J. Am. Chem. Soc., 1928, 50, 859. (b) P. M. Dharmasena, A. M. F. Oliveira-Campos, M. M. M. Raposo and P. V. R. Shannon, J. Chem. Res., 1994, (S) 296; (M) 1601. 7 L. Friedman and H. Shechter, J. Org. Chem., 1961, 26, 2522. 12 R. E. Bolton, C. J. Moody, C. W. Rees and G. Tojo, J. Chem. Soc., Perkin Trans. 1, 1987, 931. Scheme 3 Scheme 5 Scheme 6

ISSN:0308-2342    

DOI:10.1039/a704615d

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

PhMe2SiH PhMe2Si-OH + PhMe2Si-O-SiMe2Ph [(cod)RhCl]2, H2O room temp., 24 h 1c 2c 3c RR¢R¢¢SiH RR¢R¢¢Si-OH + RR¢R¢¢2Si-O-SiR¢¢R¢R [(cod)RhCl]2, H2O THF, room temp., 24 h 1a,b,d,e,f 2a,b,d,e,f 3a,b,d,e,f 400 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 400–401† Catalytic Dehydrocoupling of Silane by a Homogenous Rhodium Complex with Water† Min Shi* and Kenneth M. Nicholas Department of Chemistry and Biochemistry, The University of Oklahoma, Norman, Oklahoma 73019, USA Organosilicon hydrides are oxidized to the corresponding silanols in high yield in a homogenous phase in the presence of a small amount of water and a catalytic amount of a rhodium complex.Silanols or disiloxanes are generally formed in hydrolysis reactions of chlorosilanes. Many years ago, Sommer and Parker1 and Nagai et al.2 reported that treatment of R3SiH with excess of peroxybenzoic acid in benzene at room temperature for 12 hours gave a moderate yield of R3SiOH. Almost at the same time, Daughenbaugh also reported that the hydrolysis of organosilicon hydrides with catalysts such as palladium or ruthenium on charcoal was an excellent method of preparing the corresponding organosilanols.3 The reactions were carried out using a buffer solution rather than pure water in an effort to prevent reaction mixtures from becoming either acidic or basic.Results and Discussion During our investigation of the reactivity of dimethylphenylsilane (1c) with carbon dioxide in the presence of a catalytic amount of binuclear rhodium chloride dimer [(cod)RhCl]2 (cod=cyclooctane-1,5-diene) in tetrahydrofuran (THF), we found incidentally that the dehydrocoupling of 1c (200 mg, 1 mmol) could take place very easily to afford the corresponding silanol (2c) and 1,1,3,3-tetramethyl-1,3-diphenyldisiloxane (3c) in wet THF (50 ml water/8 ml solvent), respectively (Scheme 1).As shown in Table 1, the solvent effect was examined carefully. It was found that the solvents can dramatically change the reaction results.The use of a solvent such as benzene or pentane was confirmed to be a poorer choice than a polar solvent such as diethyl ether, dichloromethane or THF (Table 1). In the meantime, it was also found that, when wet diethyl ether or wet dichloromethane was used as solvent the formation of 2c became the dominant reaction. Thus, further reaction of 2c can be avoided by using dichloromethane as a solvent. The oxidation of the other kinds of silanes (1a,b,d,e,f) was carried out in the same reaction conditions as those mentioned above (Scheme 2).The results are summarized in Table 2. We found that, even though THF was used as solvent, the major reaction product was silanol in each case rather than disiloxane (3) and also found that 1f has no reactivity under the same reaction conditions. Other homogenous rhodium complexes such as RhCl(Ph3)3 and RhCl(CO)(Ph3)2 were also examined under the same reaction conditions for the dehydrocoupling of 1c and only 30 and 20% of 1c were converted into the products, respectively.Thus, obviously, they are not as effective as [(cod)RhCl]2. On the other hand, the catalytic oxidation dehydrocoupling reaction must be carried out in a deaerated solvent, otherwise the reaction products would be very complicated and the yield of silanol would be very low. The mechanism can be considered as a dehydrogenative coupling of a hydrosilane with water, i.e.dihydrogen is given off in the reaction. Efforts are under way to elucidate the mechanistic details of this reaction. In conclusion, these results elucidate that, using a soluble rhodium complex as a catalyst, i.e. in a homogenous phase, the oxidation of silane with water in a polar solvent can proceed efficiently. It is unnecessary to use a buffer solution for the oxidation of the silanes (1a,b,d,e) to prevent the corresponding silanols (2a,b,d,e) from further reaction and, in the case of silane 1c, the silanol (2c) can be exclusively obtained by using CH2Cl2 as solvent.Experimental Melting points were obtained with a Yanagimoto micro melting point apparatus and are uncorrected. 1H NMR spectra were determined for solutions in CDCl3 with tetramethylsilane (TMS) as internal standard on a XL-300 spectrometer. Mass spectra were recorded with a JMS D-300 instrument. All compounds reported in this paper gave satisfactory HRMS results or CH microanalyses with a Perkin-Elmer Model 240 analyser.Typical Reaction Procedure.·1,1-Dimethylphenylsilane (200 mg, 1.0 mmol) was added to a THF (8 ml) solution of [(cod)RhCl]2 (3.4 mg, 0.69Å10µ3 mmol) and then water (50 ml) was added. The reaction mixture was stirred at room temperature for 12 h and the products were qualitatively analysed by GC and isolated by a flash column (SiO2). Trimethylsilanol. dH (CDCl3) 0.23 (9 H, s, CH3), 1.67 (1 H, s, OH); MS (EI), m/z 90 (10%) [M+], 75 (100) [M+µ15] (Found: C, *To receive any correspondence.Current address: Japan Science and Technology Corporation (JST), 4-6-3 Kamishinden, Toyonaka 565, Japan. †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 The reaction of 1c in the presence of water and solvent and 0.69 mol% of rhodium complex Yield (%)a Solvent Conversion of 1c (%) 2c 3c THF Et2O CH2Cl2 Pentane Benzene 100 100 100 10 8 55 85 95 87 42 10 trace —— aIsolated yields Table 2 The results of the reaction of 1a, b,d,e,f in the presence of water and 0.69 mol% of rhodium complex in THF Yield (%)a Compound RRpRPSiH 2 3 1a 1b 1d 1e 1f Me3SiH Et3SiH Ph2MeSiH Ph3SiH (EtO)3SiH 90 94 98 98 trace trace trace ——— aYields were determined by GLC analyses using naphthalene as internal standardJ.CHEM. RESEARCH (S), 1997 401 39.94; H, 11.10%; M+, 90.0489.C3H10SiO requires C, 39.95; H, 11.18%; Mr, 90.0501). Triethylsilanol. dH (CDCl3) 0.52 (6 H, q, J 7.8 Hz, CH2), 0.95 (9 H, t, J 7.8 Hz, CH3), 2.05 (1 H, s, OH); MS (EI), m/z 132 (10%) [M+], 103 (100) [M+ µ29], 75 (90) [M+ µ57] (Found: C, 54.39; H, 12.09%; M+, 132.0970. C6H16SiO requires C, 54.48; H, 12.19%; Mr, 132.0971). 1,1-Dimethylphenylsilanol. dH (CDCl3) 0.25 (6 H, s, CH3), 1.70 (1 H, s, OH), 7.25–7.80 (5 H, m, Ar); MS (EI), m/z, 153 (10%) [M+], 137 (100) [M+µ16], 91 (70) [M+µ62] (Found: C, 63.12; H, 7.87%; M+, 152.0654.C8H12SiO requires C, 63.11; H, 7.94% Mr, 152.0658). 1,1-Diphenylmethylsilanol. Mp 88–90 °C; dH (CDCl3) 0.25 (3 H, s, CH3), 1.70 (1 H, s, OH), 7.25–7.80 (10 H, m, Ar); MS (EI), m/z 214 (10%) [M+], 198 (100) [M+µ16] (Found: C, 72.81; H, 6.57%; M+, 214.0810. C13H14SiO requires C, 78.22; H, 5.84%; Mr 214.0814). Triphenylsilanol. Mp 152–154 °C; dH (CDCl3) 1.70 (1 H, s, OH), 7.25–7.80 (15 H, m, Ar); MS (EI), m/z 276 (10%) [M+], 260 (100) [M+ µ16] (Found: C, 78.30; H, 5.82%; M+, 276.0965.C18H16SiO requires C, 78.22; H, 5.84%; Mr 276.0971). 1,1,1,3,3,3-Hexamethyldisiloxane. dH (CDCl3) 0.21 (s, CH3); MS (EI), m/z 162 (10%) [M+], 147 (100) [M+ µ15] (Found: C, 44.32; H, 11.15%; M+, 162.0891. C6H18Si2O requires C, 44.38; H, 11.17%; Mr, 162.0896). 1,1,1,3,3,3-Hexaethyldisiloxane. dH (CDCl3) 0.50 (2 H, q, J 7.8 Hz, CH2), 0.95 (3 H, t, J 7.8 Hz, CH3); MS (EI), m/z 246 (10%) [M+], 217 (15) [M+ µ29] (Found: C, 58.43; H, 12.12%; M+, 246.1832. C12H30Si2O requires C, 58.46; H, 12.27%; Mr, 246.1836). 1,1,3,3-Tetramethyl-1,3-diphenyldisiloxane. dH (CDCl3) 0.20 (6 H, s, CH3), 7.25–7.80 (5 H, m, Ar); MS (EI), m/z 286 (10%) [M+], 271 (100) [M+ µ15], 193 (70) [M+ µ93] (Found: C, 67.09; H, 7.81%; M+, 286.5208. C16H22Si2 requires C 67.07; H, 7.74%; Mr, 286.5211). Received, 1st April 1997; Accepted, 7th July 1997 Paper E/7/02189E References 1 L. H. Sommer and G. A. Parker, unpublished work cited in L. H. Sommer, Stereochemistry, Mechanism and Silicon, McGraw-Hill, New York, 1965, p. 110. 2 Y. Nagai, K. Honda and T. Migita, J. Organomet. Chem., 1967, 8, 372. 3 G. H. Barnes, Jr. and N. E. Daughenbaugh, J. Org. Chem., 1966, 31, 885.

ISSN:0308-2342    

DOI:10.1039/a702189e

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

OAc OAc Br Br 1 AcO OAc OAc 2 3 + AcO OAc 2 Zn/solvent Electrochemistry Hg, DMF, 2e– 402 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 402–403† Direct Synthesis of trans-1,4-Diacetoxycyclohexa-2,5-diene by Electrochemical Reduction of r-1,t-4-Diacetoxyt- 2,c-3-dibromocyclohex-5-ene† Latif Kelebekli,a �Umit Demirb and Yunus Kara*b aEducation Faculty of Agrý, 04200 Agrý, Turkey bDepartment of Chemistry, Atat�urk University, 25240 Erzurum, Turkey Electrochemical reduction of r-1,t-4-diacetoxy-t-2,c-3-dibromocyclohex-5-ene 1 gives only trans-1,4-diacetoxycyclohexa- 2,5-diene 2 in good yield while the commonly used Zn reduction gives a product mixture containing 2 and acetoxybenzene 3 derived from acetoxy elimination.Cyclohexadienediols have been identified as intermediates in the biological breakdown of arene oxides by Burice et al.1 These compounds are also useful intermediates for the preparation of natural aromatic compounds, quinone derivatives, 2 conduritols3 and cyclitols.4 The direct and easy electrochemical synthesis of trans-1,4-diacetoxycyclohexa-2,5-diene 2 leading to conduritol and inositols will facilitate the investigation of biological activities of this compound acting as an inhibitor of D-glycosidases and exhibiting an inhibitory effect on the growth of tumour cells.5 For the synthesis of cyclohexadienediols, a method based on 1,2-nucleophilic addition of various alkyl metal reagents such as RMgX,6 RLi7 and R3Al8 to p-benzoquinones has been used.These type of reactions result in poor yields and diastereoisomeric mixtures.9 Another method would be the direct reduction of p-benzoquinone with metal hydrides (e.g., LiAlH4, NaBH4); however, these reagents give mainly hydroquinone and a small amount of 1,4-dihydroxycyclohexadiene either with little or no stereoselectivity.10 Therefore, in order to block the formation of hydroquinone one of the double bonds must be protected by bromination before reducing with metal hydrides.Then, there are two possible ways to eliminate the bromines: (a) dehalogenation with conventional reducing reagents, or (b) electrochemical reduction. The dehalogenation of vicinal dehalides with zinc11 has been performed for the synthesis of new double bonds which can be reduced to yield the conduritols having the desired conformation. 12 In addition to zinc, magnesium, iodine and electrochemical reduction can be used.13 Electroreduction of 1,2-dibromides as a preparative method offers an attractive alternative to chemical procedures due to the potential mildness of the reaction conditions. Consequently, there has been a need for a simple, efficient, and a stereospecific procedure for the preparation of cyclohexadienediols and compounds of related structure.In this study, we report the ready synthesis of trans-1,4-diacetoxycyclohexa- 2,5-diene 2, which we first synthesized by the electroreduction of r-1,t-4-diacetoxy-t-2,c-3-dibromocyclohex- 5-ene 112 and to make comparisons between the Zn and electrochemical reductions.Reductions performed with Zn in different solvents gave mixtures of two compounds, acetoxybenzene 3 and the desired diene product 2, depending on the reaction conditions. The ratio of 2 to 3 in the reaction mixture was found to be dependent on the nature of the solvent used and the temperature. While compound 3 was the only product in DMSO at 90 °C, a mixture containing compounds 2 and 3 was obtained in diethyl ether and MeCO2H solutions at 45 °C for the reductions with Zn.In the latter reaction conditions, compound 2 was the predominant product (2:3=3:1). Cyclic voltammetry was performed on 1 using a mercury electrode in order to determine the reduction potential of 1. Only a broad and irreversible peak was observed at about µ1.5 V (SCE) at room temperature at sweep rates up to 100 mV sµ1. Cyclic voltammograms showed the same peak shape and cathodic peak potential as in the literature.14 The reductions were carried out in a divided cell on a stirred mercury electrode using DMF as solvent and 0.1 mol dmµ3 LiClO4 as supporting electrolyte.A constant potential electrolysis (cpe) at µ1.7 V of 1 gave exclusively compound 2 in high yields. It has been reported that b-haloethers and esters on treatment with Zn undergo alkoxy-halo-elimination reaction11,15 or acetoxy elimination resulting from removal of one acetoxy group by Lewis acid (ZnBr2) formed in the reduction stage after formation of 2 by debromination. In the case of acetoxyhalo- elimination, benzene or 1-acetoxy-2-bromocyclohexa- 3,5-diene would be obtained, but these compounds were never observed.The formation of compound 3 can be explained by removal of one acetoxy group by ZnBr2 yielding a cation and then an aromatization process.16 In contrast to Zn reductions, we obtained quantitatively only compound 2 by the electrochemical reduction of 1 on Hg electrodes in DMF.Similar results have been reported for the electrochemical reduction of vicinal dibromides.14,17,18 Two possible mechanisms are proposed for this reduction in these studies: first carbanion formation followed either by proton abstraction resulting in a monobromo compound or elimination of the second bromide giving compound 2. The second mechanism is the concerted elimination yielding only compound 2. In both aprotic and protic conditions, since we never observed either a monobromo compound or an aromatic compound, the mechanism of electrochemical debromination can therefore be considered as concerted.In conclusion, a short and practical synthesis of 2 has been described. We have shown that electrochemical reduction of 1 for the synthesis of 2 has some advantages over Zn reduction. These are selectivity, mild conditions of the reaction, simplicity of the procedure, and good yields of the product.Experimental Cyclic voltammetric determinations were performed using a Potentioscan Wenking POS 73 potentiostat, YEW 3022 A4 X-Y recorder. NMR spectra were recorded on a Varian-Gemini 2000 spectrometer at 200 MHz for 1H NMR and 50 MHz for 13C NMR. The IR spectra were recorded on a Mattson 1000 FTIR spectro- *To receive any correspondence (e-mail: yunus%tratauni@vm. ege.edu.tr). †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). SchemeJ. CHEM. RESEARCH (S), 1997 403 meter. In all cases reaction mixtures were separated by column chromatography. Zn Reduction of 1.·(i) To a solution of 1 (200 mg, 0.561 mmol) in DMSO (5 ml) was added 73 mg (1.1 mmol) of zinc dust and 20 mg of iodine. The mixture was magnetically stirred at 95 °C for 12 h. After cooling to room temperature, water (25 ml) and diethyl ether (25 ml) were added.The aqueous phase was extracted with diethyl ether (2Å25 ml), and the combined organic extracts were dried (Na2SO4). Evaporation of the solvent gave acetoxybenzene 3. (ii) To a solution of 1 (200 mg, 0.561 mmol) in diethyl ether (10 ml) and MeCO2H (2.5 ml) was added zinc dust (325 mg, 5 mmol). The mixture was magnetically stirred at 40–50 °C for 2 h and then enough water was added dropwise to dissolve any solid and give a clear solution. The aqueous phase was extracted with diethyl ether (2Å25 ml) and the combined organic extracts were dried (Na2SO4).Evaporation of the solvent gave acetoxybenzene 3 plus 2 in a ratio of 1:3 (combined yield: 78%). Cathodic Reduction of 1.·Cathodic reduction of 1 (300 mg, 0.842 mmol) was carried out at room temperature in a divided three-compartment-cell separated by a porous glass diaphragm. A platinum electrode and saturated calomel electrode (SCE) served as a counter electrode and reference electrode, respectively. The solvent was 50 ml of DMF containing LiClO4 (0.1 mol dmµ3).Electrolysis was carried out at constant potential (µ1.7 V) until the current became zero. Work-up as described above with diethyl ether and removal of the solvent under reduced pressure at room temperature gave 2 (96%): dH (CDCl3) 6.46 (m, 4 H), 5.70 (m, 2 H), 2.07 (s, 6 H); dC (CDCl32.32, 130.75, 66.03, 22.96; vmax (KBr)/cmµ1 2927, 1753, 1446, 1395 and 1242; mp 89–90 °C (recrystallized from hexane–CCl4).We thank Atat�urk University for financial support. We also thank Professor Dr Metin Balcý and Hasan Seçen for their helpful discussions. Received, 1st April 1997; Accepted, 23rd July 1997 Paper E/7/02167D References 1 H. Yagi, D. M. Jerina, G. J. Kasperek and T. C. Bruice, Proc. Natl. Acad. Sci. USA, 1985, 69, 1972. 2 A. Fischer and G. N. Henderson, Tetrahedron Lett., 1980, 21, 701. 3 M. Balcý, Y. S�utbeyaz and H. Seçen, Tetrahedron, 1990, 46, 3715. 4 T. Posternak, The Cyclitols, Hermann, Paris, 1st edn., 1965. 5 (a) G. Legler and M. Herrchen, FEBS Lett., 1981, 135, 139; (b) A. P. Kozikowski, A. H. Fauq, G. Powis, P. Kurian and F., T. Crews, J. Chem. Soc., Chem. Commun., 1992, 362. 6 D. E. Worral and S. Cohen, J. Am. Chem. Soc., 1936, 58, 533. 7 H. M. Crawford and M. McDonald, J. Am. Chem. Soc., 1949, 71, 2681. 8 Z. Florjanczyk, W. Kuran, S. Pasynkiewicz and G. Kwas, J. Organomet. Chem., 1976, 112, 21. 9 F. Alonso and M. Yus, Tetrahedron, 1991, 47, 7471. 10 (a) J. March, Advanced Organic Chemistry, Wiley, New York, 4th edn., 1992, p. 912; (b) H. W. Moore, K. F. West, K. Chow, M. Fernandez and N. V. Nguyen, J. Org. Chem., 1987, 52, 2537; (c) J. S. Cha and H. C. Brown, J. Org. Chem., 1993, 58, 3979. 11 J. March, Advanced Organic Chemistry, Wiley, New York, 4th edn., 1992, p. 1034. 12 H. Seçen, A. Maras, Y. S�utbeyaz and M. Balcý, Synth. Commun., 1992, 22, 2613. 13 F. Barba, A. Guirado and I. Barba, J. Org. Chem., 1984, 49, 3022. 14 K. M. O’Connel and D. H. Evans, J. Am. Chem. Soc., 1983, 105, 1473. 15 H. O. House and R. S. Ro, J. Am. Chem. Soc., 1958, 80, 182. 16 F. Alonso, I. Barba and M. Yus, Tetrahedron, 1990, 46, 2069. 17 P. M. Hudnall and D. R. Rieke, J. Am. Chem. Soc., 1973, 95, 2646. 18 C. Casanova and R. H. Rogers, J. Org. Chem., 1974, 39,

ISSN:0308-2342    

DOI:10.1039/a702167d

出版商:RSC    

年代:1997

数据来源: RSC