摘要:

J. Chem. Research (S), 1997, 88–89† Nitrosation of N-Methyl-4-tolylsulfonylguanidine† J. Ramon Leis,*a F�atima Norberto,b,c Jos�e A. Moreirac and Jim Ileyd aDepartmento de Qu�ýmica-Fisica, Faculdad de Qu�ýmica, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain bDepartmento de Qu�ýmica, Faculdade de Ci�encias, Universidade de Lisboa, 1700 Lisboa, Portugal cCECF, Faculdade de Farm�acia, Universidade de Lisboa, 1699 Lisboa, Portugal dPOCRG, Department of Chemistry, The Open University, Milton Keynes, MK7 6AA, UK Kinetic studies for the nitrosation of N-methyl-4-tolylsulfonylguanidine identify a mechanism involving rapid nitrosation of the N-methyl nitrogen atom followed by slow, general-base-catalysed proton transfer.The nitrosation of amines, amides, amidines and guanidines has received much attention, due in large part to the potential carcinogenic properties of the N-nitroso products formed. Nitrosation of amines in acidic medium occurs with rate limiting attack of the nitrosating agent on the substrate, while that of amides involves fast O-nitrosation followed by slow proton transfer from the substrate and a fast internal rearrangement to produce the N-nitrosamide.1–3 Clonidine, a guanidine with antihypertensive properties, is nitrosated by nitrous acid via slow deprotonation of the N-nitrosated substrate. 4 However, guanidines like clonidine provide a bridge between amines and amides, because, in contrast to their behaviour in acidic media, under neutral conditions nitrosation by alkyl nitrites takes place via the neutral substrate.4 To examine the effect of electron withdrawing groups on the nitrosation of the guanidine moiety, we studied the nitrosation of N-methyltoluene-4-sulfonylguanidine (1) in acidic medium and herein report our results.Experimental N-Methyl-4-tolylsulfonylguanidine (1) (TSG) was synthesised from N-methylguanidine hydrochloride using toluene-4-sulfonyl chloride in acetone–aqueous sodium hydrochloride.TSG has mp 194–196 °C; dH (CDCl3) 2.38 (3 H, s), 2.76 (3 H, s), 7.22 (2 H, d, J 8.6 Hz), 7.75 (2 H, d, J 8.6 Hz); m/z 227, 155, 91, 72. N-Methyl- N-nitroso-4-tolylsulfonylguanidine (2) (NTSG) was synthesised by the method of White.5 NTSG has mp 168–170 °C; dH 2.43 (3 H, s), 3.18 (3 H, s), 7.32 (2 H, d, J 8.1 Hz), 7.87 (2 H, d, J 8.1 Hz); m/z 256 (M+), 226 (M+µNO); lmax 257 (log e 4.08). For solubility reasons, kinetic studies were carried out at 25 °C in water–dimethylsulfoxide (9 :1 v/v) solutions at a constant ionic strength of 0.5 mol dmµ3.Kinetic analyses were performed using the initial rate method following the formation of NTSG, thus obviating problems associated with decomposition of nitrous acid. Results and Discussion Nitrosation of TSG appears to occur at the N-methyl nitrogen atom, as evidenced by the large shift in the 1H NMR of the N-methyl signal of NTSG as compared to that in TSG.The effect of [H+] on the initial rate of nitrosation of TSG (holding [TSG] and [NOµ2 ] constant) is shown in Fig. 1(a). Similar plots for the effects of [NOµ2 ] (holding [H+] and [TSG] constant) and [TSG] (holding [H+] and [NOµ2 ] constant) are shown in Figs. 1(b),(c). While the reaction is shown to have a simple, linear, first-order dependence upon [TSG] and [NOµ2 ], the plot for dependence upon [H+] is distinctly curved. The plot can be rationalised by a mechanism involving protonation of TSG in which nitrosation occurs via the unprotonated form of TSG; i.e.TSG+H+NTSGH+ (Ka=[TSG][H+]/[TSGH+]) nitrosation TSGhNTSG Under the conditions of the reaction for the variation of [H+], the total concentration of TSG, [TSG]T, is given by [TSG]T=[TSG]+[TSGH+] Thus, [TSG] =[TSG]T/(1+[H+] /Ka); as [H+] increases the amount of unprotonated TSG, the form which undergoes nitrosation, decreases. The data in Fig. 1(a) can be fitted to the rate equation vi=k3[TSG]T[NOµ2 ][H+] /(1+[H+] /Ka) from which a value of 0.39 mol dmµ3 for the acid dissocation constant, Ka, for TSG can be obtained.This corresponds to a pKa of 0.4. The third-order rate constant, k3, so obtained is contained in Table 1, together with those from the slopes of Figs. 1(b),(c) corrected for the concentration of unprotonated TSG, [TSG], at the acidity studied. The constant value of k3 from the three different investigations reveals that the nitrosation of TSG has a first-order dependence upon [TSG], [NOµ2 ] and [H+].Data for the influence of Clµ and Brµ, ions that catalyse the nitrosation of amines but not of amides, upon the initial 88 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Fig. 1 Dependence of initial rates of nitrosation of TSG upon (a) [H+], (b) [NOµ2 ] and (c) [TSG]rates of reaction (Table 2) reveal that these ions have no catalytic effect.Thus, towards nitrosation, TSG behaves like an amide, and its nitrosation should be subject to buffer catalysis. The data in Table 3 for trichloroacetic acid (TCA) buffers are consistent with this expectation. Similar correlations are observed with dichloro- (DCA) and monochloro- (MCA) acetic acid buffers, and the catalytic rate constants, kcat, for the catalysis by the basic form of the buffer, [Bµ], is obtained from plots of vi vs.[Bµ] using kcat=slope/ [NOµ2 ][H+][TSG]corrected. A Brønsted plot for the three buffers (Fig. 2) gives a value for b of 0.68. This is similar to that for clonidine,4 and implies a slow proton transfer in the rate determining step. The most likely mechanism for the nitrosation of TSG is shown in Scheme 1. We cannot be sure of the exact structure of the prototropic tautomer that reacts with NO+, but that shown in Scheme 1 is the simplest that is consistent with the experimental data.Fast, pre-equilibrium nitrosation of TSG at the most nucleophilic, methyl-bearing nitrogen atom is followed by slow protonation transfer to the medium. According to Scheme 1, the rate of nitrosation can be expressed as v=k1K1K2[TSG][NOµ2 ][H+][H2O] +kcat[TSG][NOµ2 ][H+][Bµ] For the reaction in the absence of general bases (other than solvent water) the observed deuterium isotope effect, kH3 /kD3 is 2.38.However, k3=k1K1K2[H2O], so kH3 /kD3 = kH1 KH1 KH2 [H2O]/kD1 KD1 KD2 [D2O]. The value of [H2O]/[D2O] = 1.00, and KH1 /KD1 =0.39,6 so assuming that there is a negligible isotope effect upon K2, i.e. KH2 /KD2 =1, because it does not involve a proton transfer, then the isotope effect upon the step involving proton transfer, kH1 /kD1 , is 2.38/0.39=6.1. This is consistent with the proposed step being a slow proton transfer from an acidic species to water. Thus, the sulfonylguanidine moiety behaves like amides and ureas towards nitrosation.It also has similar behaviour to that of the cyclic guanidine, clonidine. However, clonidine is a much more basic guanidine than TSG, cf. pK1s of 8.7 and 0.4 respectively; whereas it is the protonated form of clonidine that is nitrosated, it is the unprotonated form of TSG that is nitrosated. J. A. M. acknowledges the Junta Nacional de Investigaç�ao Cient�ýfica e Technologica-Portugal for a ‘Programa Ci�encia’ grant.Received, 5th November 1996; Accepted, 6th November 1996 Paper E/6/07544D References 1 G. Hallett and D. L. H. Williams, J. Chem. Soc., Perkin Trans. 2, 1980, 1371. 2 A. Castro, E. Iglesias, J. R. Leis, M. E. Pe�na and J. Vazquez Tato, J. Chem. Soc., Perkin Trans. 2, 1986, 1725. 3 J. R. Leis, M. E. Pe�na, M. J. Blanco and L. Garcia-Rio, J. Chem. Res. (S), 1992, 338. 4 F. Norberto, J. A. Moreira, E. Rosa, J. Iley, J. R. Leis and M. E. Pe�na, J. Chem. Soc., Perkin Trans. 2, 1993, 1561. 5 E. H. White, J. Am. Chem. Soc., 1955, 77, 6008. 6 A. Castro, M. Mosquera, M. F. Rodriguez Prieto, J. A. Santaballa and J. Vazquez Tato, J. Chem. Soc., Perkin Trans. 2, 1988, 1963. J. CHEM. RESEARCH (S), 1997 89 Scheme tion of TSG Fig. 2 Brønsted plot for general base catalysis of nitrosation of TSG Table 1 Dependence of observed rate constants for the nitrosation of TSG upon the concentrations of reacting species 102kp3/dm6a 102k3/dm6 Varying species [H+] [TSG]T [NOµ2 ] 105kp/sµ1a molµ2 sµ1 molµ2 sµ1 H+ · 0.005 0.01 · · 6.9 TSG 0.1 · 0.01 5.90 5.90 7.41 0.422 · 0.01 1.28 3.03 3.11b NOµ2 0.1 0.001 · 0.572 5.72 7.19 akp is the pseudo-first-order rate constant obtained from the slope of vi vs. the concentration of the varying species. kp3 is the third-order rate constant obtained by dividing kp by the concentrations of the invariant species, uncorrected for the protonation of TSG. bIn D2O. Table 2 Effect of added Clµ and Brµ ions on the initial rate of nitrosation of TSG 102[Clµ]/mol dmµ3 102[Brµ]/mol dmµ3 108vi/mol dmµ3 sµ1 ——— 3.3 20.0 — 2.0 4.0 —— 5.44 5.24 5.53 5.48 5.26 Table 3 Effect of TCA buffers on the initial rate of nitrosation of TSGa 10[TCA]/mol dmµ3 108vi/mol dmµ3 sµ1 0.429 0.858 1.287 1.717 2.575 4.56 4.90 5.11 5.28 6.13 a[TSG]T=0.001 mol dmµ3, [NOµ2 ] =0.01 mol dmµ3, pH 1.0.

ISSN:0308-2342    

DOI:10.1039/a607544d

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N N O SH Ar N N O S Ar S Me O O N N O Ar S S NH NH Ar' Me O NH2 S S N N O Ar S S+ NH NH Ar' NH2 S O S Cl O Me N N O Ar S S NH Ar' Me N C NH2 S ii. ClCH2SMe a Ar = Ph b Ar = 2-ClC6H4 i. NaOH–EtOH 1 a Ar = Ph b Ar = 2-ClC6H4 2 ii. Ar'CH = NNHC—NH2 N N O Ar S S NH Ar' a Ar' = Ph b Ar' = 4-ClC6H4 i. NaOH–MeOH 3 –HCl 4a Ar = Ph, Ar' = Ph b Ar = 2-ClC6H4, Ar' = Ph c Ar = Ph, Ar' = 4-ClC6H4 d Ar = 2-ClC6H4, Ar' = 4-ClC6H4 N C NH2 S Cl– SOCl2 –SO2 5a–d 6a–d + a Ar = Ph, Ar' = Ph b Ar = 2-ClC6H4, Ar' = Ph c Ar = Ph, Ar' = 4-ClC6H4 d Ar = 2-ClC6H4, Ar' = 4-ClC6H4 SOCl2 Pyridine Cl– Pyridine 7 J.Chem. Research (S), 1997, 90–91† A New Cyclisation of Sulfenylated Dimethyl Sulfoxide and Thiosemicarbazone Adducts using Thionyl Chloride† Lal Dhar S. Yadav* and Daya R. Pal Department of Chemistry, University of Allahabad, Allahabad, 211002 India Adducts (4a–d) obtained by nucleophilic addition of sulfenylated dimethyl sulfoxide derivatives (2a,b) to thiosemicarbazones (3a,b) undergo a new intramolecular cyclisation, involving deoxygenative demethylation, to yield 5-sulfenylated 4-aryl-2-thiocarbamoyl-1,2,3-thiadiazolidines (7a–d) on treatment with thionyl chloride. We recently published a convenient method for the synthesis of 6-sulfenylated 2-amino-1,3,4-thiadiazines from sulfenylated dimethyl sulfoxide and thiosemicarbazone adducts involving the acid-labile methylsulfinyl leaving group.1 We now report a new, efficient and simple intramolecular cyclisation of the same adducts to 5-sulfenylated 4-aryl-2-thiocarbamoyl- 1,2,3-thiadiazolidines (7a–d) involving deoxygenative demethylation on treatment with thionyl chloride.These sulfenylated heterocycles were required in connection with the development of potential pharmacological agents and agrochemicals. 1,2 The synthetic sequence leading to the formation of 7 is depicted in Scheme 1. The formation of adducts 4 and their cyclisation to 7 were highly diastereoselective.The crude isolates were checked by 1H NMR for their diastereomeric ratios to avoid inadvertent alteration of these ratios during subsequent isolation and purification (see Experimental section). The reaction of chloromethyl methyl sulfoxide and the sodium salt of 5-aryl-2-sulfanyl-1,3,4-oxadiazoles 1 in refluxing ethanol for 5 h furnished 2. Nucleophilic addition of sulfur- stabilised carbanions, generated in situ by the action of sodium methoxide on 2 in methanol at room temperature, to the C�N of thiosemicarbazones 3 followed by quenching with dilute hydrochloric acid afforded 4 in 65–72% yield with high diastereoselectivity (92–96%).Adducts 4 underwent a new cyclisation, involving deoxygenative demethylation, on treatment with thionyl chloride in pyridine, resulting in 60–69% yield of 7 with 93–96% diastereoselectivity. The evolution of methanethiol on treatment of 7 with methyl iodide in ethanol followed by alkaline hydrolysis with potassium hydroxide provides chemical evidence for the presence of the thiourea residue in 7.The easy and wide availability of the requisite substrates and the simple operations under mild conditions makes the present cyclisation a potential general synthetic method for a variety of cyclic systems. Experimental Mps were determined in open glass capillaries and are uncorrected. IR spectra were recorded in KBr on a Perkin-Elmer 993 spectrophotometer. 1H NMR spectra were recorded on a Perkin- Elmer R-32 (90 MHz) spectrometer using [2H6]dimethyl sulfoxide as solvent and SiMe4 as internal standard.Mass spectra were recorded on a JEOL D-300 mass spectromter at 70 eV. Elemental analyses were carried out in a Coleman automatic carbon, hydrogen and nitrogen analyser. 5-Aryl-2-methylsulfinylmethylsulfanyl-1,3,4-oxadiazoles 2 and 1-[1- a r y l - 2 - ( 5 - a r y l - 1 , 3 , 4 - o x a d i a z o l - 2 - y l s u l f a n y l) - 2 - ( m e t h y l s u l f i n y l)e t h y l ] - thiosemicarbazides 4.·These were prepared according to the method described earlier1 and recrystallised from ethanol. The crude product 4 was recrystallised from ethanol to give a diastereomeric mixture (a97:s3; in the crude isolates the ratio was 92–96:8–4, determined by 1H NMR spectroscopy) which was again recrystallised from ethanol to obtain an analytical sample of a single diastereomer 4 (Tables 1 and 2).On the basis of 1H NMR and published data,5–7 compounds 4 were assigned erythro (syn) stereochemistry, as their 1H NMR spectra exhibit a coupling constant, JSCH,NCH=4 Hz, which is smaller than that of the very minor (s3%) diastereomer (threo or anti), JSCH,NCH=10 Hz. 5 - Aryl- 2 - (4 - thiocarbamoyl- 1,2,3 - thiadiazolidin- 5 - ylsulfanyl) - 1,3,4 - 90 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J.Chem. Research (M). Scheme 1oxadiazoles 7. General Procedure.·A solution of 4 (20 mmol) and thionyl chloride (2.0 ml, 25 mmol) in pyridine (50 ml) was refluxed for 8 h. The pyridine was evaporated under reduced pressure at 40 °C and the residue obtained was washed with water and recrystallised from ethanol to give a diastereomeric mixture (a97:s3%; in the crude isolates the ratio was 93–96:7–4, determined by 1H NMR spectroscopy) which on second recrystallisation from ethanol furnished an analytical sample of a single diastereomer 7 (Tables 1 and 2).Compounds 7 were assigned cis stereochemistry, as the coupling constant, J4,5=4.5 Hz, for 7 was lower than that for the very minor (s3%) diastereomer (trans), J4.5=11 Hz.7–9 Received, 26th July 1996; Accepted, 18th November 1996 Paper E/6/05234G References 1 L. D. S. Yadav and S. Sharma, Synthesis, 1993, 864. 2 L. D. S. Yadav and S. Sharma, Gazz. Chim.Ital., 1994, 124, 11. 3 R. W. Young and K. H. Wood, J. Am. Chem. Soc., 1955, 77, 400. 4 S. Giri, H. Singh and L. D. S. Yadav, Agric. Biol. Chem., 1976, 40, 17. 5 T. Mukaiyama and N. Iwasawa, Chem. Lett., 1984, 753. 6 R. Tanikaga, K. Hamamura and A. Kaji, Chem. Lett., 1988, 977. 7 L. D. S. Yadav and S. Sharma, Synthesis, 1992, 919. 8 S. E. Booth, P. R. Jenkins and C. J. Swain, J. Chem. Soc., Chem. Commun., 1991, 1248. 9 M. Hirayama, K. Gamoh and N. Ikekawa, Chem. Lett., 1982, 491.J. CHEM. RESEARCH (S), 1997 91 Table 1 Yields, mps, molecular formulae and elemental analyses of compounds 2, 4 and 7 Found (required) (%) Yield Mp Molecular Compd. (%) (T/°C) formula C H N 2a 2b 4a 4b 4c 4d 7a 7b 7c 7d 74 70 72 68 65 71 68 60 69 62 164–166 171–173 151 180–182 157–158 146 155–156 130 147–148 158–160 C10H10N2O2S2 C10H9ClN2O2S2 C18H19N5O2S3 C18H18ClN5O2S3 C18H18ClN5O2S3 C18H17Cl2N5O2S3 C17H15N5OS3 C17H14ClN5OS3 C17H14ClN5OS3 C17H13Cl2N5OS3 47.3 (47.2) 41.5 (41.6) 50.0 (49.9) 46.1 (46.2) 46.0 (46.2) 42.9 (43.0) 50.6 (50.9) 46.6 (46.8) 47.0 (46.8) 43.2 (43.4) 4.1 (4.0) 3.0 (3.1) 4.2 (4.4) 3.9 (3.9) 3.7 (3.9) 3.3 (3.4) 3.6 (3.8) 3.2 (3.0) 3.0 (3.2) 2.7 (2.8) 11.1 (11.0) 9.6 (9.7) 16.3 (16.2) 15.2 (15.0 15.1 (15.0) 13.8 (13.9) 17.6 (17.4) 15.9 (16.1) 16.0 (16.1) 15.0 (14.9) Table 2 Spectral data for compounds 2, 4 and 7 Compd.vmax/cmµ1 dH (J in Hz) M+ 2a 1030 (S�O) 2.59 (s, 3 H, Me), 4.25 (s, 2 H, CH2), 7.31–7.76 (m, 5 H, ArH) 254 2b 1035 (S�O) 2.62 (s, 3 H, Me), 4.28 (s, 2 H, CH2), 7.48–8.03 (m, 4 H, ArH) 288 4a 1030 (S�O) 2.56 (s, 3 H, Me), 3.72 (d, 1 H, J 4.0, SCH), 4.92 (d, 1 H, J 4.0, NCH), 7.32–7.82 (m, 10 H, ArH), 8.40–9.22 (br, 4 H, NHNHCSNH2) 433 4b 1035 (S�O) 2.58 (s, 3 H, Me), 3.71 (d, 1 H, J 4.0, SCH), 4.92 (d, 1 H, J 4.0, NCH), 7.30–8.06 (m, 9 H, ArH), 8.40–9.20 (br, 4 H, NHNHCSNH2) 467 4c 1030 (S�O) 2.52 (s, 3 H, Me), 3.74 (d, 1 H, J 4.0, SCH), 4.94 (d, 1 H, J 4.0, NCH), 7.34–8.09 (m, 9 H, ArH), 8.44–9.18 (br, 4 H, NHNHCSNH2) 467 4d 1035 (S�O) 2.57 (s, 3 H, Me), 3.76 (d, 1 H, J 4.0, SCH), 4.96 (d, 1 H, J 4.0, NCH), 7.36&ndas, ArH), 8.41–9.15 (br, 4 H, NHNHCSNH2) 503 7a 3310–3365 (NH, NH2) 4.20 (d,. 1 H, J 4.5, 5-H), 4.58–4.73 (br, 3 H, NH, NH2), 5.23 (d, 1 H, J 4.5, 4-H), 7.28–7.76 (m, 10 H, ArH) 401 7b 3305–3370 (NH, NH2) 4.10 (d, 1 H, J 4.5, 5-H), 4.62–4.82 (br, 3 H, NH, NH2), 5.26 (d, 1 H, J 4.5, 4-H), 7.31–7.93 (m, 9 H, ArH) 435 7c 3315–3360 (NH, NH2) 4.19 (d, 1 H, J 4.5, 5-H), 4.69–4.90 (br, 3 H, NH, NH2), 5.28 (d, 1 H, J 4.5, 4-H), 7.40–8.02 (m, 9 H, ArH) 435 7d 3320–3375 (NH, NH2) 4.22 (d, 1 H, J 4.5, 5-H), 4.70–4.89 (br, 3 H, NH, NH2), 5.24 (d, 1 H, J 4.5, 4-H), 7.39–8.04 (m 8 H, ArH) 471

ISSN:0308-2342    

DOI:10.1039/a605234g

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 92–93† Oxidations of Benzyl Alcohol by Hydrogen Peroxide in the Presence of Complexed Peroxoniobium(V) Species† C�elia Maria de Souza Batista,a Simone Coriolano de Souza Melo,a Georges Gelbardb and Elizabeth Roditi Lachter*a aLaborat�orio de Cat�alise Org�anica, Departamento de Qu�ýmica Org�anica, Instituto de Qu�ýmica, da Universidade Federal do Rio de Janeiro, Ilha do Fund�ao, CT, Bloco-A, CEP:21949-900, Rio de Janeiro, RJ, Brazil bInstitut de Recherches sur la Catalyse du CNRS, 2 Av.A.Einstein, F-69626, Villeurbanne, France The influence of ligands around peroxo niobium complexes and of the ratio of oxygen-source substrates towards the efficiency of the niobium(V)-catalysed oxidation of benzyl alcohol to benzaldehyde by hydrogen peroxide has been analysed: the use of ligands such as phenylphosphonic acid and 2,2p-bipyridyl associated with peroxoniobate gave efficient systems. The oxidation of alcohols to aldehydes or ketones is an important transformation in organic synthesis.1 Oxidation of secondary alcohols to ketones can be carried out with hydrogen peroxide and transition metal complexes of Mo,2–4 V,5 Ti6 and Cr.7,8 The oxidative ability towards the alcoholic function of a series of peroxomolybdenum complexes has been evaluated. 9,10 Recently we became involved in the chemistry of peroxoniobium(V) complexes in the oxidation of alcohols and olefins. In the present work, systems comprising peroxoniobium( V) species complexed with phenylphosphonic acid and 2,2p-bipyridyl have been checked for the catalytic oxidation of benzyl alcohol by hydrogen peroxide.In all experiments the catalytic systems were formed in situ by mixing appropriate amounts of peroxoniobium(V) species and ligands. The reactions were carried out under biphasic conditions where the solvent was 1,2-dichloroethane and the oxidant was an aqueous solution of hydrogen peroxide. The results presented in Table 1 show that in the reaction without catalyst (entry 1) the yield of benzaldehyde was s0.1%, while with NbCl5 and without ligand the yield of benzaldehyde after 9 h was 13.9% (entry 2).In the presence of the ligand phenylphosphonic acid and an excess of H2O2 in relation to benzyl alcohol, we also achieved a higher turnover (entry 6) than that reported in the literature9,11 for other peroxo systems in the oxidation of the same alcohol. In the presence of 2,2p-bipyridyl (entry 10) we similarly achieved a higher turnover, but an excess of H2O2 decreased the conversion of benzyl alcohol (entries 9 and 11).In all reactions the main product was the benzaldehyde, but in some cases, with an excess of H2O2, we verified the presence of benzoic acids (entries 3, 4, 6 and 11). In conclusion, this investigation has shown that complexes of niobium, together with 2,2p-bipyridyl is effective for the oxidation of benzyl alcohol to benzaldehyde in excellent yield without oxidation to benzoic acid.Experimental Benzyl alcohol and 1,2-dichloroethane (DCE) was purified by distillation. Phenylphosphoric acid, tetrabutylammonium hydroxide and 2,2p-bipyridyl were commercially available, high-purity products (Aldrich) and were used as received. Hydrogen peroxide solution [30% (w/w)] was purchased from Per�oxidos do Brasil S/A and niobium pentachloride from Companhia Brasileira e mineraç �ao (CBMM). Typical Experimental Procedure (see Table 1 for Times and Amounts).·In a round-bottomed flask was added sequentially 1,2-dichloroethane (50 ml), benzyl alcohol (1 mmol), NbCl5, the ligand, tetrabutylammonium hydroxide and aqueous H2O2 (30% w/w).The oxidations were run at 40 °C. Aliquots of the reaction were withdrawn at various times, and the amount of the product were determined by GC analysis on an SE-54 column after reactions with triphenylphosphine to consume the excess of H2O2. We gratefully acknowledge Conselho Nacional de Desenvolvimento Cient�ýfico e Tecnol�ogico (CNPq) and Fundaç�ao Universit�aria Jos�e Bonif�acio (FUJB) for financial support.Received, 28th August 1996; Accepted, 18th November 1996 Paper E/6/05944I References 1 R. A. Sheldon, New Developments in Selective Oxidation, ed. G. Cente and T. Trifir�o, Elsevier, Amsterdam, 1990, pp. 1–41. 2 Y. Kurusu and Y. Masuyama, Polyhedron, 1986, 5, 289. 92 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Table 1 Oxidation of benzyl alcohol (1 mmol) by hydrogen peroxide in the presence of peroxoniobium(V) species complexed with phenylphosphonic acid (PPA) and 2,2p-bipyridyl (BP) Conversion Selectivity (%) H2O2 Time of alcohol Entry Catalytic system (mmol)a (mmol) (t/h) (%) Benzoic acid Benzaldehyde Turnoverb 1 · 1 30 0.1 · 100 · 2 NbCl5+1 equiv.QOH (0.25) 1 9 13.9 · 100 0.56 3 NbCl5+1 equiv. PPA+1 equiv Q+ OH (0.1) 1 2 15.9 1.2 98.8 1.59 4 NbCl5+1 equiv. Q+OH+1 equiv. PPA 2 2 25.5 4.8 95.2 2.55 5 NbCl2+1 equiv. PPA+1 equiv. Q+ OH (0.25) 1 5 53.9 · 100 2.16 6 NbCl5+1 equiv. QOH+1 equiv. PPA (0.25) 2 2 84.5 5.6 94.4 3.38 7 NbCl5+1 equiv. PPA+1 equiv. Q+ OH (0.50) 1 5 86.6 · 100 1.73 8 NbCl5+1 equiv. BP (0.10) 1 2 13.5 · 100 1.35 9 NbCl5+1 equiv. BP (0.10) 2 2 7.5 · 100 0.75 10 NbCl5+1 equiv. BP (0.25) 1 2 82.4 · 100 3.3c 11 NbCl5+1 equiv. BP (0.25) 2 2 19.0 6.2 93.8 0.76 aQOH=Tetrabutylammonium hydroxide. bDefined as T=mmol products/mmol catalyst. cA value of 1.92 is reported in ref. 9. dReaction carried out in DCE at 40 °C.3 B. M. Trost and Y. Masuyama, Tetrahedron Lett., 1984, 25, 173. 4 Y. Ishii, K. Yamawaki, T. Ura, H. Yamada, T. Yoshida and M. Ogawa, J. Org. Chem., 1988, 53, 3587. 5 K. Kaneda, Y. Kwanishi, K. Jitsukawa and S. Teranishi, Tetrahedron Lett., 1983, 24, 5009. 6 K. Yamawaki, Y. Ishii and M. Ogawa, Chem. Express, 1986, 1, 95. 7 J. Muzart, Chem. Rev., 1992, 94, 113. 8 S. A. Mohand, A. Levina and J. Muzart, Synth. Commun., 1995, 25, 2051. 9 O. Bartolini, S. Campestrini, F. Furia, G. Di Modera and G. Valle, J. Org. Chem., 1987, 52, 5467. 10 S. Campestrini, P. Fulvio Di Furia Rossi and A. Torboli, J. Mol. Catal., 1993, 83, 95. 11 J. Muzzart and A. Niait, J. Mol. Catal., 1991, 66, 1

ISSN:0308-2342    

DOI:10.1039/a605944i

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

J. Chem. Research (S), 1997, 94–95† Complex Formation by Dithionate(V) Ion† Robert Greatrex and Duncan C. Munro* School of Chemistry, The University of Leeds, Leeds LS2 9JT, UK Complexes of dithionate(V) ion with several cations are obtained as the solid potassium salts; in solution, stabilities are less than the corresponding oxalato complexes. Dithionic acid, the oxoacid of sulfur(V), has been known for some time and has moderate stability at ordinary temperatures. 1 The free acid has not been isolated, although moderately concentrated solutions can be prepared.Many salts of the anion S2O6 2µ are known, and there are reports of its functioning as the counter-ion with cationic complexes formed by other ligands. On a few occasions, a single dithionate ion enters the coordination sphere, with2 Co in [Co(NH3)5 .S2O6]Cl and K4[Co(CN)5 .S2O6] .6H2O, and with Cr in [Cr(NH3)5 .S2O6]+ salts,3 also4 in cis[CrL2F(S2O6)] where L is either 1,2-diaminoethane or 1,3-diaminopropane.In some ways, the dithionate(V) ion may be compared with the oxalate ion C2O2µ 4 which is known to function as a chelating ligand in the formation of numerous complexes. In aqueous solutions, chelating ligands are known generally to form more stable complexes than the corresponding monodentate ligands, and this suggests that chelate complex formation might take place between some cations and the dithionate(V) ion. We now report the preparation and characterisation of a number of dithionate(V) complexes, isolated as the potassium salts, together with estimates of stability in solution for three such complexes.Experimental Calcium dithionate and barium dithionate were obtained as described.5 By treatment of their solutions with solutions containing calculated amounts of sulfuric acid or potassium sulfate, followed by separation of precipitated sulfate, the free acid and potassium salt were obtained in solution. For studies of stability constants, the sodium salt was obtained similarly and recovered by evaporation.To obtain complexes, appropriate amounts of precipitated hydroxides or carbonates of metallic elements were dissolved in the free acid solution, and the potassium salt solution added. After filtration, products were obtained by evaporation to small bulk and crystallisation on cooling. (The aluminium compound was obtained by dissolving aluminium turnings in potassium hydroxide solution, with subsequent addition of an appropriate amount of free acid.) Characterisation was usually achieved by thermogravimetric analysis over the temperature range 50–400 °C, and sometimes confirmed by volumetric methods, using either oxidation with dichromate for determination of the dithionate ion, or EDTA for divalent cations. The compounds obtained from preparations as above are listed in Table 1 together with the results of thermogravimetric analysis.Stabilities in Solution.·Experimental estimates of stability constants (log b2) were made for complex formation with Ni, Zn and Cd by potentiometric titration in a background of sodium perchlorate at 1.0 mol dmµ3, and at 24 °C, by the following procedure.To a solution (100 cm3) in NaClO4 of the appropriate element at 0.002 mol dmµ3 as sulfate or nitrate was added a solution of sodium dithionate [0.25 mol dmµ3 (in NaClO4)]. A cleaned metal electrode of the element concerned was immersed in the solution and its potential was measured relative to a saturated calomel electrode between successive additions of dithionate solution up to a mole ratio of 50 :1.Reliability of electrode behaviour was confirmed by consistencies within a series of readings, and between titration runs. Results and Discussion Solid dithionate(V) salts when heated decompose to the corresponding sulfates with loss of sulfur dioxide. With hydrated salts and complexes, it is often possible to distinguish two separate stages.For example with CaS2O6 .4H2O losses take place (a) between 120 and 200 °C and (b) between 250 and 320 °C, corresponding to loss of water and sulfur dioxide respectively. On this basis, it has been possible in Table 1 to match formulae to the results from thermogravimetric analysis. Close parallels are shown with corresponding oxalato complexes, for example with copper(II);1 cf. Na2[Cu- (C2O4)2] .2H2O. For the Ti and Zr complexes, inclusion of oxo or hydroxo groups is necessary to account for the analytical results; cf.the ion6 [Zr(C2O4)2(OH)2(H2O)2]2µ. From the potentiometric measurements at excess dithionate, values for log b2 have been obtained by methods of iterative calculation. Dithionic acid is a strong acid, and the known7 value of pKa makes it possible to discount possibilities of protonation of the mononuclear complex species in the conditions pertaining. 94 J. CHEM. RESEARCH (S), 1997 *To receive any correspondence (e-mail: r.greatrex@chem.leeds. ac.uk).†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 Thermogravimetric analysis of dithionate(V) complexes Loss of mass (%)a First stage Second stage Overall Compound f r f r f r K2Be(S2O6)2 K3Ce(S2O6)3 K2Ti(OH)2(S2O6)2.1.6H2O K2Zr(OH)2(S2O6)2.2H2O K2Ni(S2O6)2.6H2O K2Cu(S2O6)2.2H2O K2Zn(S2O6)2.4H2O K3Al(S2O6)3.3H2O —— 11.0 6.4 19.0 7.0 13.5 — —— 10.9 6.4 19.1 7.2 14.5 — —— 26.3 25.6 22.6 25.5 24.4 — —— 25.2 26.1b 22.7 25.7 23.9 — 31.3 25.9 37.3 32.0 41.5 32.5 37.9 36.4 31.4 26.1 36.1 32.5 41.8 32.9 38.4 36.3 af=found; r=formula requirement; bCorresponds with water from (OH)2 in the second stage.Values found for log b2 are: Ni, 4.70�0.7; Zn, 2.40�0.1; Cd, 2.46�0.1, and these may be compared with the range of values listed7 for the corresponding bis-oxalato complexes: Ni, 7.6–7.9; Zn, 7.6; Cd, 4.1–5.4.They indicate a generally lower stability for the complexes of the dithionate(V) ion. We acknowledge substantial assistance with experimental work from numerous final-year undergraduate students. Received, 6th August 1996; Accepted, 2nd December 1996 Paper E/6/05479J References 1 N. V. Sidgwick, The Chemical Elements and their Compounds, Oxford, 1950, vol. II, pp. 940–942; M. Schmidt and W. Siebert, in Comprehensive Inorganic Chemistry, ed. J. C. Bailar, Pergamon Press, Oxford, New York, 1973, vol. 2, pp. 877–878. 2 M. Calvet, Afinidad, 1981, 38, 131. 3 J. M. Coronas and J. Casabo, An. Quim., 1974, 70, 335. 4 J. Ribas, J. Casabo and M. D. Baro, Thermochim. Acta, 1981, 47, 271. 5 R. Pfanstiel, Inorg. Synth., 1946, 2, 167. 6 Dictionary of Inorganic Compounds, ed. J. E. Macintyre, Chapman and Hall, London, 1992. 7 Stability Constants, The Chemical Society, London, Special Publications No. 17, 1964, pp. 360–364 and 25 (Supplement No. 1), 1971, pp. 245–250. J. CHEM. RESEARCH (S), 1

ISSN:0308-2342    

DOI:10.1039/a605479j

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

96 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 96–97† Reactions of Carbonyl Compounds in Basic Solutions. Part 27.1 Alkaline Hydrolysis of Bridged Benz[de]isoquinolin- 1-ones: Torsionally Distorted Lactams† Keith Bowden* and Simon P. Hiscocks Department of Biological and Chemical Sciences, Central Campus, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK Rate coefficients have been measured for the alkaline hydrolysis of 2,3-ethanoxy- and 2,3-propanamino-2,3-dihydro- 1H-benz[de]isoquinolin-1-ones‡ in 70% (v/v) dimethyl sulfoxide–water at several temperatures and of N,N-dimethyl- 1-naphthamide in water: the relative rates of hydrolysis, activation parameters and other studies indicate the importance of the torsional distortion of the lactam nitrogen and steric ‘bulk’ factors in controlling reactivity.There have been a number of studies of the alkaline hydrolysis of strained lactams2–4 and amides.5 Structural distortion of an amide or lactam group from planarity has been demonstrated to increase the reactivity towards alkaline hydrolysis.Several bicyclic lactams have been used to establish a relationship between the degree of distortion and the susceptibility towards hydrolysis.3,4 However, these lactams all involve alkyl–carbonyl and aryl–amine linkages. The present study is an investigation of the alkaline hydrolysis of the torsionally distorted lactams, the 2,3-bridged 2,3-dihydro-1H-benz[de]isoquinolin-1-ones 1, in which the lactams have aryl–carbonyl and alkyl–amine linkages, while being locked by a 1,8-naphthalene template.The effects of structure and substitution on the rates of reaction, as well as the activation parameters, are considered to enable an analysis of the reactivity and reaction mechanism. Experimental Materials.·N,N-Dimethyl-1-naphthamide (2b) was prepared by the reaction of 1-naphthoyl chloride with dimethylamine.6 The 2,3-bridged 2,3-dihydro-1H-benz[de]isoquinolin-1-ones 1a–d were prepared by the reaction of 8-formyl- or 8-benzoyl-1-naphthoyl chloride in chloroform with an excess of ethanolamine or 1,3-diaminopropane. The reaction products were purified by use of a Chromatotron (dichloromethane–ethyl acetate). 1a and 2b are known compounds6,7 and were recrystallised from ethyl acetate. Melting points are uncorrected. IR spectra were recorded on a Zeiss Specord M-80 spectrophotometer. 1H NMR spectra were recorded on a JEOL EX270 FT spectrometer with Me4Si as internal reference.Chemical shifts are expressed as d/ppm. The purity of the lactams and amide was monitored by IR and 1H and 13C NMR spectroscopy, as well as mass spectroscopy. The mps of the compounds, after repeated recrystallisation and drying under reduced pressure (P2O5), were either in agreement with literature values6,7 or are shown below, together with their spectral details and elemental analysis. 10,11,12,12a-Tetrahydro-9H-benzo[de]pyrimidino[1,2-b]isoquinolin- 7-one (1b) (32%), mp 155–158 °C (colourless needles from ethyl acetetate); vmax/cmµ1 (CHCl3) 1649 (C�O); ([2H6]Me2SO) 3.51–4.20 (m, 6 H, CH2), 4.88 (1 H, NH), 6.11 (s, 1 H, CH), 7.63–8.21 (m, 6 H, arom.); m/z (70 eV) 238 (M+) (Found: C, 75.2; H, 6.2; N, 11.65%). C15H14N2O requires C, 75.6; H, 5.9; N, 11.75%). 11a-Phenyl-9,10-dihydro-11aH-benzo[de][1,3]oxazolo[3,2-b]isoquinolin- 7-one (1c) (13%), mp 151–153 °C (colourless needles from ethyl acetate); vmax/cmµ1 (CHCl3) 1648 (C�O); dH (CDCl3) 3.28–4.60 (m, 4 H, CH2), 7.13–8.52 (m, 11 H, arom.); m/z (70 eV) 301 (M+) (Found: C, 79.4; H, 4.95; N, 4.55.C20H15NO2 requires C, 79.7; H, 5.0; N, 4.65%). 12a-Phenyl-10,11,12,12a-tetrahydro-9H-benzo[de]pyrimidino[1,2- b]isoquinolin-7-one (1d) (5%), mp 255–256 °C (colourless needles from ethyl acetate); vmax/cmµ1 (CDCl3) 1647 (C�O); dH (CDCl3) 1.58–2.96 (m, 6 H, CH2), 7.14–8.53 (m, 11 H, arom.); 5.05 (1 H, NH); m/z (70 eV) 314 (M+) (Found: C, 80.25; H, 5.75;l N, 8.9. C21H18N2O requires C, 80.25; H, 5.75; N, 8.9%).The solvents were purified as described previously.8 Measurements.·Rate coefficients for the alkaline hydrolysis of the lactams and amide were determined by use of a Perkin-Elmer Lambda 5 or 16 UV–VIS spectrometer. The cell temperature was controlled to within �0.05 °C by means of a Haake DC3 circulator. The reactions were followed at the wavelengths shown in Table 1. The procedure used as that described previously.9 The alkaline hydrolysis of 1a, 1b and 2b is of first order in both substrate and hydroxide anion.The rate coefficient in 70% (v/v) aqueous dimethyl sulfoxide (DMSO) and other solvent systems are shown in Table 1. The activation parameters are shown in Table 2. The products of the alkaline hydrolysis of 2b are the anion of 1-naphthoic acid and dimethylamine, that of 1a is the anion of 8-(1,3-oxazolidin- 2-yl)-1-naphthoic acid 3a and that of 1b is the anion of 8-(hexahydropyrimidin-2-yl)-1-naphthoic acid 3b.Both the structures of 3a and 3b were determined by 1H NMR spectroscopy of the solution of the product in 70% (v/v) [2H6]DMSO–D2O. The corresponding acids could not be obtained pure on acidification, as cyclisation occurred. Both 1c and 1d were very resistant to alkaline hydrolysis. No significant reaction could be observed for either substrate after 12 h at 60 °C in 70% (v/v) aqueous DMSO and 0.3 mol dmµ3 base. Discussion A mechanistic pathway for the alkaline hydrolysis of lactams under present study is shown in Scheme 1.2,4 The first step is the addition of base to form the adduct 4, which collapses to form 5.The latter rapidly transforms to the final product 3. The lactams 1a and 1b are relatively reactive in their alkaline hydrolysis, cf. ref. 2. The relative rate of hydrolysis in water of 1a (extrapolated) to 2b at 60.0 °C is ca. 60. This is considerably less than the factor of ca. 107 noted by Brown’s group4 in passing from N-methylacetanilide to their most distorted lactam, 3,4-dihydro- 1,4-ethanoquinolin-2(1H)-one (6). The torsional distortions in 1a and 1b are not as great as that in 6, but the effect on the rates appears to persist in systems with aryl– carbonyl and alkyl–amino linkages.The lactam 1a has a fused ring consisting of a five-membered ring containing nitrogen and oxygen, whereas 1b has a six-membered ring containing nitrogen and nitrogen.The small difference in their rates of hydrolysis, a factor of ca. 2, indicates that the effect is achieved by ring fusion itself and does not depend on ring size. A comparison of the activation parameters for the hydrolysis of 1a and 1b with those for related systems indicates that the hydrolysis of the latter shows rather large DH‡ *To receive any correspondence (email: keithb@essex.ac.uk). †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). ‡9,10-Dihydro-11aH-benzo[de]oxazolo[3,2-b]- and 10,11,12,12atetrahydro - 9H- benzo[de]pyrimidino[1,2 - b] - isoquinolin - 7 - ones respectively.J. CHEM. RESEARCH (S), 1997 97 values and very small negative values of DS‡. This would be in accord with partial fission of the carbon–nitrogen bond in the ratedetermining step releasing ring strain angle and torsional effects in the fused ring system11 and indicates the rate determining step to be k2 in Scheme 1, cf.refs. 2 and 4. The resistance to hydrolysis of 1c and 1d apparently arises from a steric ‘bulk’ effect. Dunitz et al.12 have shown that nucleophilic attack at the carbonyl group of an amide occurs with stereoelectronic control at a preferred angle. This is when the nucleophile approaches the carbonyl bond along a line that forms an angle of about 107° to the plane of the bond. The lactams 1 were modelled.13 These results show that the carbonyl carbon, nitrogen and acyl carbon are almost coplanar with the naphthalene ring and that the nitrogen is disposed towards an sp3 pyramidal geomete ethanoxy or propanamino link which is itself out of this plane.The links will sterically inhibit hydroxide anion attack from that face of the plane. However, for 1a and 1b the face of the plane having the acyl hydrogen substituent is free for attack at the preferred angle, whereas for 1c and 1d this face of the plane contains the acyl phenyl substituent which almost completely blocks such a preferred attack by its steric ‘bulk’.All the ring (pseudo) esters of 8-acyl-1-naphthoic acids previously studied14 have at least one comparatively free face for nucleophilic attack and are relatively reactive. We thank the UK SERC and Rh�one-Poulenc Rorer for the award of a CASE studentship (to S. P. H.) and Drs M. J. Ashton and M. N. Palfreyman for their advice and interest.Received, 18th November 1996; Accepted, 3rd December 1996 Paper E/6/07785D References 1 Part 26, K. Bowden and A. Brownhill, J. Chem. Soc., Perkin Trans. 2, in press. 2 K. Bowden and K. Bromley, J. Chem. Soc., Perkin Trans. 2, 1990, 2111, and references cited therein. 3 G. M. Blackburn, C. J. Skaife and I. T. Kay, J. Chem. Res., 1980, (S) 294; (M) 3650. 4 V. Somayaji and R. S. Brown, J. Org. Chem., 1986, 51, 2676; Q.-P. Wang, A. J. Bennet and R.S. Brown, Can. J. Chem., 1990, 68, 1732; Q.-P. Wang, A. J. Bennet, R. S. Brown and B. D. Santarsiero, J. Am. Chem. Soc., 1991, 113, 5757. 5 H. Slebocka-Tilk and R. S. Brown, J. Org. Chem., 1987, 52, 805; A. J. Bennet, Q.-P. Wang, H. Slebocka-Tilk, V. Somayaji and R. S. Brown, J. Am. Chem. Soc., 1990, 112, 6383; H, Slebocka- Tilk, A. J. Bennet, J. W. Keillor, R. S. Brown, J. P. Guthrie and A. Jodham, J. Am. Chem. Soc., 1990, 112, 8507; H. Slebocka-Tilk, A. J. Bennet, H. J.Hogg and R. S. Brown, J. Am. Chem. Soc., 1991, 113, 1288; R. S. Brown, A. J. Bennet and H. Slebocka-Tilk, Acc. Chem. Res., 1992, 25, 481. 6 J. von Braun, Ber. Dtsch. Chem. Ges., 1904, 37, 2678. 7 R. Sato, K. Oikawa, T. Goto and M. Saito, Bull. Chem. Soc. Jpn., 1988, 61, 2238. 8 K. Bowden and R. S. Cook, J. Chem. Soc. B, 1971, 1765. 9 K. Bowden and K. Bromley, J. Chem. Soc., Perkin Trans. 2, 1990, 2103. 10 C. A. Bunton, B. Nayak and C. O’Connor, J. Org. Chem., 1968, 33, 572. 11 H. Maskill, The Physical Basis of Physical Organic Chemistry, Oxford University Press, Oxford, 1985. 12 H. B. B�urgi, J. D. Dunitz and E. J. Shefter, J. Am. Chem. Soc., 1973, 95, 5065. 13 Nemesis v1.1, Interactive Molecular Modelling, Oxford Molecular, Oxford, 1991. 14 K. Bowden and A. M. Last, J. Chem. Soc., Perkin Trans. 2, 1973, 358; K. Bowden and F. A. El Kaissi, J. Chem. Soc., Perkin Trans. 2, 1977, 526; F. Anvia, K. Bowden, F. A. El Kaissi and V. Saez, J. Chem. Soc., Perkin Trans. 2, 1990, 1809. Table 1 Rate coefficients (k2) for the alkaline hydrolysis of the lactams 1a and 1b in 70% (v/v) aqueous DMSOa 103 k2/dm3 molµ1 sµ1 Compound At 30.0 °C At 40.0 °C At 50.0 °C At 60.0 °C l/nmb 1a 0.920 2.58 6.74 16.0 325 (5.27)c (3.25)d 1b 1.87 5.63 14.6 38.3 350 2b (0.0360)e 240 aRate coefficients were reproducible to �3%. bWavelengths used to monitor alkaline hydrolysis. cIn 50% (v/v) aqueous DMSO. dIn 30% (v/v) aqueous DMSO. eIn water, i.e. 1.5% (v/v) aqueous DMSO. Table 2 Activation parameters for the alkaline hydrolysis of the lactams 1a and 1b in 70% (v/v) aqueous DMSO at 30.0 °Ca Compound DH‡/kcal molµ1 DS‡/cal molµ1 Kµ1 1a 1b 2ab 18.5 19.5 15.6 µ11 µ7 µ30 aValues of DH‡ and DS‡ are accurate to �300 cal molµ1 and �1 cal molµ1 Kµ1, respectively. bIn water (k2 equal to 6.0Å10µ6 and 15.2Å10µ4 dm3 molµ1 sµ1 at 25.0 and 100.4 °C, respectively). 5,1

ISSN:0308-2342    

DOI:10.1039/a607785d

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

N OH N O M 1 2 N O N N RuII N N O– N N N O N N O N O 3 RuIII N N N O 4 + 98 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 98–99† Bis(quinolin-8-olato) Complexes of Ruthenium. Synthesis, Characterization and Cyclic Voltammetric Studies† Nimai Chand Pramanik and Samaresh Bhattacharya* Department of Chemistry, Inorganic Chemistry Section, Jadavpur University, Calcutta 700 032, India Reaction of quinolin-8-ol (HQ) with [Ru(bpy)Cl3] (bpy=2,2p-bipyridine) in the presence of NEt3 affords [RuII(bpy)(Q)2] which shows a RuII–RuIII oxidation at µ0.16 V vs.SCE and a RuIII–RuIV oxidation at 1.06 V vs. SCE; its oxidation by Ce4+ gives [RuIII(bpy)(Q)2]+ which has been isolated and characterized as the perchlorate salt. There is continuing interest in the chemistry of ruthenium,1 primarily due to the fascinating electron-transfer properties exhibited by complexes of this metal. Variation of the coordination environment around ruthenium plays a key role in modulating the redox properties of its complexes. Complexation of ruthenium by ligands of different types is of particular interest in this respect and we have been active in this area.2 In the present work we have used quinolin-8-ol (HQ, 1; H stands for the dissociable phenolic hydrogen) as the principal ligand.The quinolin-8-olate anion (Qµ) binds metal ions as a didentate N,O-coordinator forming a five-membered chelate ring (2). It may be noted here that the chemistry of ruthenium quinolin-8-olates appears to have received relatively less attention.3 Herein we report our studies on two bis(quinolin- 8-olato) complexes of ruthenium.To satisfy the remaining two coordination sites of the Ru(Q)2 moiety, 2,2p-bipyridine (bpy) has been used as the co-ligand. The synthesis, characterization and redox properties of the [RuII(bpy)(Q)2] (3) and [RuIII(bpy)(Q)2]+ (4) complexes are described. [Ru(bpy)(Q)2] was synthesized in good yield from the reaction of [Ru(bpy)Cl3] with HQ in refluxing ethanol in the presence of NEt3.The composition of the complex was con- firmed by microanalysis. Magnetic susceptibility measurements showed that it is diamagnetic, as expected for complexes of ruthenium(II) (low-spin, d6, S=0). Out of three possible geometric isomers of [Ru(bpy)(Q)2], we assign structure 3 to it in analogy with the stereochemistry of other [RuII(bpy)(N·O)2] complexes.2f,4 Comparison of the IR spectrum of [Ru(bpy)(Q)2] with that of [Ru(bpy)Cl3] shows that in the former complex the v(Ru·Cl) stretch near 330 cmµ1 is absent and many new vibrations are present in the fingerprint region due to coordinated Qµ ligands.The electronic spectrum of [Ru(bpy)(Q)2] in acetonitrile solution showed three intense absorptions in the visible region at 570 (e=8000), 450 (e=12 000) and 370 (e=9300 dm3 molµ1 cmµ1) which are probably due to allowed metal-to-ligand change-transfer transitions. Similar spectral behaviour has been observed previously for other [Ru(bpy)(N·O)2] complexes.2f,4 A cyclic voltammogram of [Ru(bpy)(Q)2], recorded in acetonitrile (Fig. 1, Table 1), showed one reversible oxidation at µ0.16 V which is assigned to the [RuII(bpy)(Q)2]–[RuIII (bpy)(Q)2]+ couple, followed by an irreversible oxidation at 1.06 V due to the [RuIII(bpy)(Q)2]+–[RuIV(bpy)(Q)2]2+ couple. A reduction response, observed at µ1.92 V, is assigned to the [RuII(bpy)(Q)2]–[RuII(bpy.µ)(Q)2]µ couple. It is interesting to note here that a gradual decrease in the potential of the ruthenium(II)–ruthenium(III) couple was observed in the series [Ru(bpy)3]2+, 1.30 V; [Ru (bpy)2(Q)]+, 0.48 V; [Ru(bpy)(q)2], µ0.16 V; [Ru(Q)3], *To receive any correspondence.†This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Fig. 1 Cyclic voltammogram (scan rate 50 mV sµ1) of [Ru(bpy)(Q)2] in CH3CN (0.1 mol dmµ3 TEAP) at a platinum electrode (298 K) Table 1 Cyclic voltammetric data: E°298/V(DEp/mV)a Compound RuII–RuIII RuIII–RuIV bpy reductions Ru(bpy)(Q)2] [Ru(bpy)2(Q)]ClO4 µ0.16 (80) 0.48 (80) 1.06e µ1.92 (780) µ1.55 (60) µ1.77 (60) [Ru(bpy)3](ClO4)2 c 1.35 (62) µ1.33 (56) µ1.52 (70) µ1.76 (66) [Ru(Q3]d µ0.70 (70) 0.66 (130) aConditions: solvent, acetonitrile; supporting electrolyte, tetramethylammonium perchlorate (TEAP; 0.1 mol dmµ3); working electrode, platinum; reference electrode, SCE; solute concentration, 10µ3 mol dmµ3; E°298=0.5 (Epa+Epc), where Epa and Epc are anodic and cathodic peak potentials; DEp=EpaµEpc; scan rate, 50 mV sµ1.bRef. 3b. cRef. 5. dRef. 3a. eEpa.J. CHEM. RESEARCH (S), 1997 99 µ0.70 V (Table 1). This reflects the ability of phenolate oxygen coordination to stabilise ruthenium(III) better than the pyridine nitrogen. The reversibility of the ruthenium(II)–ruthenium(III) couple in [Ru(bpy)(Q)2] and its low potential indicates that the oxidised species may be stable on a much longer time scale.Chemical oxidation of [Ru(bpy)(Q)2] by aqueous Ce4+ solution indeed afforded the stable [Ru(bpy)(Q)2]+, which was isolated and characterized as the perchlorate salt. The IR spectrum of [Ru(bpy)(Q)2]ClO4 is very similar to that of [Ru(bpy)(Q)2], except that intense bands at 1100 and 621 cmµ1 are displayed by the former, indicating the presence of ClO4 µ. [Ru(bpy)(Q)2]ClO4 is one-electron paramagnetic (meff=1.88 mB) as expected for the +3 state of ruthenium (low spin d5, S=1/2).In 1:1 dichloromethane–toluene solution at 77 K it shows a rhombic EPR spectrum (Fig. 2), with three distinct resonances at g1=2.403, g2\2.153 and g3=1.879. The cyclic voltammogram displayed by the oxidized complex is identical with that of its ruthenium(II) precursor, indicating no gross change in stereochemistry (4). In acetonitrile solution [Ru(bpy)(Q)2]ClO4 behaves as a 1:1 electrolyte (LM=150 S cm2 dm3 molµ1) and shows intense change-transfer transitions at 750 (e=2600) 460 (shoulder, e=8000) and 410 nm (e=9700 dm3 molµ1 cmµ1), together with a weak ligand-field transition6 at 1500 nm (e=170 dm3 molµ1 cmµ1).Reduction of [RuIII(bpy)(Q)2]+ by hydrazine in acetonitrile solution gave back [RuII(bpy)(Q)2] quantitatively, which was identified by its characteristic electronic spectrum. Experimental Commercial ruthenium trichloride (Arora Matthey, Calcutta, India) was converted into RuCl3.3H2O by repeated evaporation to dryness with concentrated hydrochloric acid. 2,2p-Bipyridine and quinolin-8-ol were purchased from Loba, Bombay, India. [Ru(bpy)Cl3] was prepared by a published procedure.7 Purification of acetonitrile and preparation of tetraethylammonium perchlorate (TEAP) for electrochemical work were performed as reported.8 Microanalyses (CHN) were performed using a Perkin-Elmer 240C elemental analyser.IR spectra were obtained on a Perkin- Elmer 783 spectrometer with samples prepared as KBr pellets.Electronic spectra were recorded on a Hitachi 330 spectrophotometer. Magnetic susceptibilities were measured using a PAR 155 vibrating sample magnetometer. X-band EPR spectroscopy was performed on a Varian E 109C spectrometer fitted with a quartz Dewar for measurement at 77 K (liquid nitrogen) and spectra were calibrated with diphenylpicrylhydrazyl (DPPH) (g=2.0037). Solution electrical conductivities were measured using a Philips PR9500 bridge with a solute concentration of about 10µ3 mol dmµ3.Electrochemical measurements were made using the PAR model 273 electrochemistry system as before.3b All electrochemical experiments were performed under dinitrogen. Data were collected at 298 K and are uncorrected for junction potential. Synthesis.·[Ru(bpy)(Q)2]. [Ru(bpy)Cl3] (200 mg, 0.55 mmol) and HQ (175 mg, 1.21 mmol) were taken together in ethanol (40 cm3).To the solution was added NEt3 (0.25 cm3, 1.80 mmol) and the resulting solution was heated at reflux under a dinitrogen atmosphere. The initial light yellow solution turned deep brown within 10 min. Refluxing was continued for an additional 2 h, then the solvent was evaporated and the solid mass obtained was washed thoroughly with hexane. Recrystallization from dichloromethanehexane (1:1 v/v) gave [Ru(bpy)(Q)2] as a dark brown crystalline solid (235 mg, 78%) (Found: C, 61.5; H, 3.8; N, 10.3.C28H20N4O2Ru requires C, 61.6; H, 3.7; N, 10.27%). [Ru(bpy)(Q)2]ClO4. To a stirred solution of [Ru(bpy)(Q)2] (200 mg, 0.37 mmol) in acetonitrile (30 cm3) was added an aqueous solution of cerium(IV) ammonium sulfate (240 mg, 0.38 mmol). The initial dark brown solution turned brownish-green within 15 min. Stirring was continued for an additional 30 min. The solution was then filtered to remove any insoluble material and to the filtrate was added saturated aqueous NaClO4 (10 cm3).After the solution had been allowed to stand for 2 h at room temperature, the [Ru(bpy)(Q)2]ClO4, which had separated out as a microcrystalline solid, was collected by filtration, washed with little cold water and dried in vacuo over P4O10 (yield 195 mg, 82%) (Found: C, 52.0; H, 3.3; N, 8.6. C28H20ClN4O6Ru requires C, 52.1; H, 3.1; N, 8.7%). Financial assistance received from the Department of Science and Technology, New Delhi (SR/OY/C-08/93), is gratefully acknowledged.Thanks are due to Professor Animesh Chakravorty, Indian Association for the Cultivation of Science, Calcutta, for his help. Received, 2nd August 1996; Accepted, 29th November 1996 Paper E/6/05408K References 1 (a) K. R. Seddon, Coord. Chem. Rev., 1981, 35, 41; 1982, 41, 79; 1985, 67, 171; (b) K. Kalyansundaram, Coord. Chem. Rev., 1982, 46, 159; (c) E. A. Seddon and K. R. Seddon, The Chemistry of Ruthenium, Elsevier, Amsterdam, 1984; (d) B. K. Ghosh and A.Chakravorty, Coord. Chem. Rev., 1989, 25, 239; (e) W. T. Wong, Coord. Chem. Rev., 1994, 131, 45. 2 (a) J. Chakravarty and S. Bhattacharya, Polyhedron, 1996, 15, 257 and references cited therein; (b) N. Ghatak and S. Bhattacharya, Trans. Met. Chem., 1996, 21, 158; (c) J. Chakravarty and S. Bhattacharya, Polyhedron, 1996, 15, 1047; (d) P. K. Sinha, J. Chakravarty and S. Bhattacharya, Polyhedron, 1996, 15, 2931; (e) P. K. Sinha, J. Chakravarty and S. Bhattacharya, Polyhedron, 1997, 16, 81; (f) N. Ghatak and S. Bhattacharya, Trans. Met. Chem., in press. 3 (a) G. K. Lahiri, S. Bhattacharya, B. K. Ghosh and A. Chakravorty, Inorg. Chem., 1987, 26, 4324; (b) S. Bhattacharya, Polyhedron, 1993, 12, 235; (c) M. Menon, A. Pramanik, N. Bag and A. Chakravorty, J. Chem. Soc., Dalton Trans., 1995, 1417 and references cited therein. 4 (a) N. Ghatak, J. Chakravarty and S. Bhattacharya, Polyhedron, 1995, 14, 3591; (b) N. C. Pramanik and S. Bhattacharya, Polyhedron, 1997, 16, in press. 5 N. E. Tokel-Takvarian, R. E. Hemingway and A. J. Bard, J. Am. Chem. Soc., 1973, 95, 6582. 6 S. Bhattacharya and A. Chakravorty, Proc. Indian Acad. Sci. (Chem. Sci.), 1985, 95, 159. 7 S. Anderson and K. R. Seddon, J. Chem. Res. (S), 1979, 74. 8 (a) D. T. Sawyer and J. L. Roberts Jr, Experimental Electrochemistry for Chemists, Wiley, New York, 1974, pp. 167–215; (b) M. Walter and L. Ramaley, Anal. Chem., 1973, 45, 165. Fig. 2 X-Band EPR spectrum of [Ru(bpy)(Q)2]ClO4 in frozen (77 K) CH2Cl2–PhMe (1:1 v/v)

ISSN:0308-2342    

DOI:10.1039/a605408k

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

100 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 100–101† Nucleophilic Reactivity of N-Phosphorylated Ethyleneimine† Charlotte Le Roux, Agnes M. Modro and Tomasz A. Modro* Centre for Heteroatom Chemistry, Department of Chemistry, University of Pretoria, Pretoria 0002, South Africa The diesters of N-phosphorylated ethyleneimine (aziridine) are unreactive towards alkylating agents, but after being converted into the ionic monoesters, they undergo facile N-methylation with MeI, followed by fast opening at the aziridinium ring by the iodide ion; the results can be related to the bis-alkylating reactivity of N-phosphorylated nitrogen mustards.The bisalkylating (cross-linking) reactivity of phosphoramide mustard 1a, released in the in vivo degradation of an antitumor drug cyclophosphamide, is attributed to the intramolecular cyclization of its conjugate base 1b to an aziridinium ion 2, the reactive intermediate in the sequence of two ring-opening reactions with an external nucleophile Y (Scheme 1).1 We have demonstrated the participation of aziridinium ions of the type 2 in the degradation of N-(2-chloroethyl)phosphoramidates (N-phosphorylated nitrogen mustards).2 The results obtained so far indicate that the accumulation of the negative charge at the phosphate group is a prerequisite for a facile 1,3-cyclization, while the positively charged nitrogen atom in 2 is responsible for the high electrophilicity of the aziridine carbon atoms.There is, however, a single literature report3 according to which N-(diethylphosphoryl) ethyleneimine 3a reacts with benzyl chloride yielding the N-benzylated, ring-opened product 4a; the reaction can be explained by the mechanism given in Scheme 2 involving the initial N-benzylation of the substrate. In view of the available reports on the alkylation of phosphoramidates,4 it seems unlikely that the nitrogen atom in a neutral substrate like 3a would be nucleophilic enough to be alkylated to a quaternary derivative, susceptible to the ring-opening reaction. We have prepared the N-phosphorylated ethyleneimine 3a and its O,O-dimethyl (3b) and O,O-diphenyl (3c) analogues and tested those three substrates towards alkylation (using benzyl chloride or iodomethane) under various conditions. No reaction with PhCH2Cl was observed for 3a or 3b upon boiling in chlorobenzene for 30 h or on heating the substrates neat at 100 °C for 24 h; 3b underwent under those conditions partial degradation (most likely resulting from facile O-demethylation5) to a complex mixture of phosphorus- containing products. All three substrates proved unreactive towards iodomethane in CDCl3 solutions at 40 °C for 24 h.We did not, therefore, confirm the earlier reports3 on the N-alkylation of 3a, and we demonstrate in this work that the ionization of the phosphate function has a dramatic effect on the nucleophilic reactivity of the N-phosphorylated ethyleneimine.Phosphoramidates 3 were converted into the corresponding monoanionic salts 5 either by the nucleophilic O-dealkylation (3a, 3b) or by alkaline hydrolysis (3c) (Scheme 3). The salts 5 were then subjected to the alkylation reactions in methanolic solutions at room temperature. With benzyl chloride the reactivity of 5 was very high, but non-selective, leading to a complex mixture of phosphorus-containing products, all giving rise to 31P NMR signals at about 11 ppm (no P·N bond cleavage).The reaction with MeI, on the other hand, yielded in each case the expected products 6 (scheme 4) as a single product, with the reactivity of the salts decreasing in the order 5ba5aa5c. Presumably the products 6 are formed via the attack of Iµ ion at the N-methylated zwitterionic derivative of 5 (see Scheme 2); the formation of the latter intermediate confirms the structural condition of a substrate (the anionic phosphate group) necessary for the N-alkylation to occur.The N-methylated derivative of 5 can be considered a model for an intermediate 2 (Scheme 1), postulated as a key intermediate in the bis-alkylation sequence of phosphoramide mustard.6 The enhanced basicity (and nucleophilicity) of the aziridine nitrogen in the ionic substrates 5, allowing the ring- *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J.Chem. Research (M). Scheme 1 Scheme 2 Scheme 3 Reagents: i, LiI, butan-2-one; ii, aq. NaOH Scheme 4J. CHEM. RESEARCH (S), 1997 101 opening via the N-protonated (or N-alkylated) intermediate, was confirmed in the following experiment. When 5b was incubated in a weakly acidic solution in D2O (pD24) at 40 °C for 1 h, it was quantitatively converted into the N-(2-hydroxyethyl) phosphoramidate 7b, presumably via the attack of water at the N-protonated form of the substrate (Scheme 5).It is interesting to note that in the conjugate acid of 5b, it is the aziridine carbon, not the phosphorus atom, that represents the electrophilic reaction centre, and that the reaction leads to a phosphoramidate product, not to P·N bond cleavage, as is usually observed for a phosphoric amide system under acidic conditions.7 As expected, all ions 5 were found to be perfectly stable when incubated in the D2O–[2H5]- pyridine (4 :1, v/v) at 40 °C for 48 h.Since in that medium the N-protonation of 5 should be negligible, no reaction takes place, notwithstanding the presence of highly nucleophilic species. In conclusion, our results indicate that the biologically important bis-alkylating reactivity of N-phosphorylated mustards is closely related to a local pH of the medium, which should control the deprotonation equilibria (1am1b, Scheme 1), critical for the 1,3-cyclization and the nucleophilic ringopening steps.Experimental NMR spectra were recorded on a Bruker AC 300 spectrometer in CDCl3 (unless otherwise stated) and d values are given relative to SiMe4 (1H, 13C) or 85% H3PO4 (31P). 13C NMR spectra are given as proton-decoupled, but the proton-coupled spectra gave the expected patterns of signals. Mass spectra were recorded on a Varian MAT-212 double-focusing direct-inlet spectrometer at an ionization potential of 70 eV. Elemental analyses (C, H, N) were performed at the Chemistry Department, University of Cape Town. N-Phosphorylated aziridines 3 were prepared from the corresponding phosphorochloridates and ethyleneimine (prepared according to the literature procedure8) in the presence of triethylamine in diethyl ether at 10 °C.After filtration through a layer of MgSO4–Celite, the solution was washed with 10% aqueous K2CO3, dried (MgSO4) and concentrated under reduced pressure. 3a, oil (59%); bp 139–141 °C) at 1 mmHg; dH 1.29 (6 H, t, J 6.8 Hz), 2.10 (4 H, d, J 15.5 Hz), 4.10 (4 H, m); dC 16.2 (s), 24.2 (d, J 6.3 Hz), 63.3 (d, J 4.2 Hz); dP 15.9; m/z 179 (6%, M+), 166 (100, M+µCH), 138 (39, M++1µC2H4N), 110 (99, M++1µC2H4NµC2H4). 3b,9 oil (62%); bp 83–84 °C at 0.7 mmHg; dH 2.14 (4 H, d, J 15.5 Hz), 3.77 (6 H, d, J 10.8 Hz); dC 23.4 (d, J 6.0 Hz), 52.9 (d, J 5.5 Hz); dP 18.4. 3c, oil (51%); bp 187–189 °C at 0.7 mmHg; dH 2.31 (4 H, d, J 16.4 Hz), 7.22 (10 H, m); dC 25.5 (d, J 6.5 Hz), 120.2 (s), 125.2 (s), 129.8 (d, J 8.6 Hz), 149.2 (s); dP 6.8; m/z 276 (100%, M++1), 262 (22, M+µCH), 166 (20, M++1µCHµ2ÅPh).Salts 5a and 5b were prepared from 3a and 3b by heating the solutions of substrates with 1 mol equiv. of LiI in butan-2-one under reflux for 3 h. The precipitate was filtered off, washed several times with anhydrous CHCl3 and dried under high vacuum. 5a, white powder (81%); dH (D2O) 1.18 (3 H, t, J 7.2 Hz), 1.89 (4 H, d, J 14.3 Hz), 3.91 (2 H, m); dP 13.9 (Found: C, 30.20; H, 6.05; N, 8.85. C4H9LiNO3P requires C, 30.59; H, 5.78; N, 8.92%). 5b, white powder (81%); dH (D2O) 1.91 (4 H, d, J 14.2 Hz), 3.57 (3 H, d, J 10.5 Hz); dP 15.1 (Found: C, 24.95; H, 5.08; N, 9.55. C3H7LiNO3P requires C, 25.20; H, 4.93; N, 9.79%). 5c was prepared from 3c by heating a suspension of 3c in 0.15 M aqueous NaOH containing 1 mol equiv. of NaOH until a homogeneous solution was obtained (ca. 17 h). Most of the water was removed under reduced pressure and complete drying was achieved by means of the Dean–Stark method. 5c, white solid (64%); dH (D2O) 1.98 (4 H, d, J 14.6 Hz), 7.13 (5 H, m); dP 10.5 (Found: C, 43.00; H, 4.25; N, 6.30. C8H9Na- NO3P requires C, 43.45; H, 4.10; N, 6.33%). Methylation reactions of salts 5 were carried out by incubating a solution of 5 in CD3OD (1.4 mL per mmol of 5) in the presence of MeI (2.8 mol equiv.) at room temperature and monitoring the reaction progress by 31P NMR spectroscopy. After a certain period of time (24, 52 and 72 h for 5b, 5a, and 5c, respectively) the spectrum showed complete disappearance of substrate and the formation of a single phosphorus-containing product.The solvent and the excess of MeI were evaporated under reduced pressure, and the residue was washed with anhydrous ether and dried under high vacuum. 6a, white powder (98%); dH (CD3OD+NaOD; pD211) 1.18 (3 H, t, J 7.0 Hz), 2.50 (3 H, d, J 9.5 Hz), 3.00 (2 H, m), 3.23 (2 H, t, J 6.4 Hz), 3.30 (2 H, m); dP 10.9 (Found: C, 19.85; H, 4.20; N, 4.50.C5H12ILiNO3P requires C, 20.09; H, 4.05; N, 4.69%). 6b, white hygroscopic solid (100%); dH (CD3OD+NaOD; pD211) 2.50 (3 H, d, J 9.1 Hz), 3.01 (2 H, m), 3.25 (2 H, t, J 6.6 Hz), 3.36 (3 H, d, J 11.0 Hz); dP 12.3 (Found: C, 16.44; H, 3.85; N, 4.77. C4H10ILiNO3P requires C, 16.86; H, 3.54; N, 4.92%). 6c, white powder (88%); dH (CD3OD+NaOD; pD211) 2.51 (3 H, d, J 9.6 Hz), 3.02 (2 H, m), 3.21 (2 H, t, J 6.4 Hz), 7.05 (5 H, m); dP 8.1 (Found: C, 29.60; H, 3.50; N, 3.70 (C9H12INaNO3P requires C, 29.78; H, 3.33; N, 3.86%).Hydrolysis of Lithium Methyl N,N-Ethylenephosphoramidate (5b).·Salt 5b was dissolved in D2O (0.050 g in 0.4 mL), the pD of the solution was adjusted to ca. 4 with CF3CO2D and the solution was incubated at 40 °C for 1 h. NMR (1H and 31P) spectra of the solution demonstrated complete disappearance of 5b and the formation of a single product, identical with that obtained previously in the alkaline hydrolysis of 2-methoxy-2-oxo-1,3,2-oxazaphospholidine. 2 The reaction was repeated on a larger scale in the H2O–CF3CO2H solution and the product 7b was isolated as an amorphous, hygroscopic solid (95%); dH (D2O) 2.79 (2 H, m), 3.38 (3 H, d, J 10.9 Hz), 3.45 (2 H, t, J 5.6 Hz); dP 10.2 (Found: C, 22.10; H, 5.95; N, 8.50.C3H9LiNO4P requires C, 22.38; H, 5.63; N, 8.70%). Financial assistance from the University of Pretoria and the Foundation for Research Development is gratefully acknowledged. Received, 18th November 1996; Accepted, 3rd December 1996 Paper E/6/07791I References 1 T. W. Engle, G. Zon and W. Egan, J. Med. Chem., 1982, 25, 1347. 2 C. le Roux, A. M. Modro and T. A. Modro, J. Org. Chem., 1995, 60, 3832; H. Wan and T. A. Modro, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 108, 155. 3 O. C. Dermer and G. E. Ham, Ethyleneimine and other Aziridines, Academic Press, New York, 1969. 4 J. I. G. Cadogan, R. K. Mackie and J. A. Maynard, J. Chem. Soc. C, 1967, 1356; B. C. Challis, J. A. Challis and J. N. Iley, J. Chem. Soc., Perkin Trans. 2, 1978, 813; U. Ragnarsson and L. Grehn, Acc. Chem. Res., 1991, 24, 285. 5 M. D. M. Gray and D. J. H. Smith, Tetrahedron Lett., 1980, 21, 859. 6 M. Colvin, R. B. Brundrett, M.-N. N. Kan, I. Jardine and C. Fenslau, Cancer Res., 1976, 36, 1121. 7 D. A. Tyssee, L. P. Bauscher and P. Haake, J. Am. Chem. Soc., 1973, 95, 8066; P. Haake and G. W. Allen, J. Am. Chem. Soc., 1973, 95, 8080; T. A. Modro, M. A. Lawry and E. Murphy, J. Org. Chem., 1978, 43, 5000. 8 V. P. Wystrach, D. W. Kaiser and F. C. Schafer, J. Am. Chem. Soc., 1955, 77, 5915. 9 B. Davidowitz and T. A Modro, S. Afr. J. Chem., 1982, 35, 63. Scheme 5

ISSN:0308-2342    

DOI:10.1039/a607791i

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

102 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 102–103† A Facile Synthesis of Some Benzothiopyrano- [4,3-b]pyrroles† Christopher D. Gabbutt, John D. Hepworth* and B. Mark Heron Department of Chemistry, University of Central Lancashire, Preston PR1 2HE, UK A simple synthesis of some benzothiopyrano[4,3-b]pyrroles from benzothiopyran-4-ones is described which has been used to prepare the novel heterocyclic system 4H-naphtho[1p,2p: 5,6]thiopyrano[4,3-b]pyrrole. Since the isolation1 and characterisation2 of the thiopyrano- [2,3,4-dc]indole (chuangxinmycin) 1 from the soil microorganism Actinoplanes jinanensis and its application by the Chinese as an antibiotic, particularly effective for the treatment of Escherischia coli infections,1 there have been several reports on the synthesis of this ring system,3 and of the isomeric thiopyrano[2,3,4-cd]indole 2,4 thiopyrano[3,4-b]indole 35 and thiopyrano[2,3-b]indole 4.6 The syntheses of thiopyrano[ 3,4-b]pyrroles5 and the benzothiopyrano-[3,4-b]- 57 and -[4,3-b]-indoles 68 have also been described.As part of our study of condensed heterocycles containing the benzothiopyran unit,9 we have devised a simple synthesis of some new benzothiopyrano[4,3-b]pyrroles, a ring system which has previously received scant attention.10 The route has been adapted to provide access to fused analogues. Discussion The base-catalysed condensation of a-methylene ketones with glyoxal monohydrazones and subsequent reduction of the resulting hydrazono ethylidene derivatives affords g-aminoketones which undergo a facile cyclisation to give pyrroles.11 More recently, phenylacetylaldehyde has been shown to condense with glyoxal mono(N,N-dimethylhydrazone) in the presence of morpholine to afford 3-aminopyrroles directly.12 The acidity of the C-3 methylene protons of 2,3-dihydro- 1-benzothiopyran-4-one is well established.13 When glyoxal mono(N,N-dimethylhydrazone)12,14 was refluxed with 2,2-dimethyl-2,3-dihydro-1-benzothiopyran-4-one15 7 (R=H) in anhydrous ethanol containing one equivalent of potassium tert-butoxide, the 3-(N,N-dimethylhydrazonoethylidene) ketone 8 (R=H) was obtained after elution of the reaction mixture from silica (Scheme 1).The 1H NMR spectrum of 8 (R=H) displayed singlets at d 1.64 and 3.06 assigned to the methyl groups at C-2 and the dimethylamino function, respectively. The alkenyl and azomethine protons appeared as an AM pattern at d 6.67 and 7.82 respectively, with a coupling constant of 9.3 Hz.The Z-stereochemistry of 8 was implied from nuclear Overhauser effect difference spectroscopic studies. Irradiation of the signal for the geminal methyl groups resulted in enhancement of the signal for the alkenyl proton, confirming their close proximity. Space-filling models further substantiate the proposed s-trans conformation of 8, since significant steric interactions are indicated between the �N·NMe2 group and the carbonyl function when an s-cis arrangement is adopted. The condensation of the benzothiopyran-4-one 7 (R=6-Me) and the naphtho[2,1-b]thiopyran-1-one 7 (R=5,6-benzo) with glyoxal mono(N,N-dimethylhydrazone) gave the respective ketones 8 (R=6-Me) and 8 (R=5,6-benzo), which have comparable 1H NMR data with 8 (R=H).The reductive cyclisation of 8 (R=H) was achieved on refluxing in ethanol containing an excess of sodium dithionite. The pyrrole 9 (R=H) was obtained in moderate yield after recrystallisation.The 1H NMR spectrum of this compound displayed triplets at d 6.21 and 6.84 and a broad singlet at d 8.4 which are assigned to H-3, H-2 and NH, respectively. Complete H–D exchange of the NH proton was observed after a sample was allowed to stand overnight with D2O before recording the 1H NMR spectrum. The exchange also resulted in the simplification of the signals for the pyrrole ring protons, which now appeared as doublets with J=2.7 Hz.The low-field signal at ca. d 8.4 exhibited by 9 (R=8,9-benzo) is attributed to the peri proton (H-11). It is likely that the formation of the pyrrole ring proceeds via an imine which on further reduction affords an amine. Subsequent 5-exo-trig ring closure with dehydration results in a 2H-pyrrole which undergoes a 1,5-H shift to give the pyrrole 9 (R=H). Cyclisation of 8 (R=Me and 8 (R=5,6-benzo) was accomplished in an identical manner, although the benzologue 9 (R=8,9-benzo), a new ring system, was somewhat unstable and gradually darkened on standing at room temperature. Experimental 1H NMR spectra were recorded on a Bruker WM 250 MHz instrument for solutions in CDCl3; J values are given in Hertz.Melting points are uncorrected. Flash chromatographic separations were performed on Sorbsil C60 silica gel. Preparation of 3-(Dimethylhydrazonoethylidene)-2,2-dimethylthiochroman- 4-ones.·Potassium tert-butoxide (10 mmol) was added in a single portion to a stirred solution of the thiochroman-4-one 7 (10 mmol) and glyoxal mono(N,N-dimethylhydrazone) (40 mmol) in anhydrous ethanol (35 cm3).The resulting solution was boiled *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Scheme 1 Reagents and conditions: i, glyoxal mono(dimethylhydrazone), KOBut, EtOH, heat; ii, excess sodium dithionite, EtOH, heatunder reflux for 2.5 h.On cooling, the ethanol was evaporated and the resulting sticky brown semi-solid was taken up in water (100 cm3) and extracted with ethyl acetate (4Å50 cm3). Removal of the dried (Na2SO4) solvent afforded a dark brown oil which was eluted from silica gel with 20% (v/v) ethyl acetate–hexane to afford the title compounds as orange oils or solids. 3-(Dimethylhydrazonoethylidene)- 2,2-dimethylthiochroman-4-one 8 (R=H) (54%) was a bright orange oil which decomposed upon distillation; dH 1.64 (6 H, s, 2-Me), 3.06 [6 H, s, N(CH3)2], 6.68 (1 H, d, J 9.3, �CH·CH�N·), 7.17–7.23 (2 H, m, Ar-H), 7.34–7.40 (1 H, m, Ar-H), 7.82 (1 H, d, J 9.3, CH�N·), 8.18 (1 H, dd, J 8.7, 1.7, 5-H) (Found: C, 65.6; H, 6.6; N, 10.1; S, 11.5.C15H18N2OS requires C, 65.7; H, 6.6; N, 10.2; S, 11.7%). 3-(Dimethylhydrazonoethylidene)- 2,2,6-trimethylthiochroman-4-one 8 (R=6-Me) (70%) was obtained as bright orange plates from light petroleum (bp 40–60 °C), mp 90–91 °C; dH 1.62 (6 H, s, 2-Me), 2.35 (3 H, s, 6-Me), 3.05 [6 H, s, N(CH3)2], 6.65 (1 H, d, J 9.3, �CH·CH�N), 7.11 (1 H, d, J 8.0, 8-H), 7.22 (1 H, dd, J 8.1, 1.8, 7-H), 7.82 (1 H, d, J 9.3, ·CH�N·), 7.99 (1 H, d, J 1.7, 5-H) (Found: C, 66.4; H, 7.0; N, 9.7; S, 10.8.C16H20N2OS requires C, 66.6; H, 7.0; N, 9.7; S, 11.1%). 3-(Dimethylhydrazonoethylidene)-2,2-dimethylbenzo[f]thiochroman- 4-one 8 (R=5,6-benzo) (30%) was obtained as bright orange crystals from light petroleum (bp 40–60 °C), mp 118–119.5 °C; dH 1.70 (6 H, s, 2-Me), 3.07 [6 H, s, N(CH3)2], 6.70 (1 H, d, J 9.3, �CH·CH�N), 7.26 (1 H, d, J 8.7, 10-H), 7.42–7.49 (1 H, m, Ar-H), 7.59–7.66 (1 H, m, Ar-H), 7.75–7.80 (2 H, m, Ar-H), 7.97 (1 H, d, J 9.3, ·CH�N·), 9.28 (1 H, dd, J 8.6, 1.8, 5-H) (Found: C, 70.2; H, 6.3; N, 8.6; S, 9.7.C19H20N2OS requires C, 70.3; H, 6.2; N, 8.6; S, 9.9%). Preparation of 4H-Benzo[5,6]thiopyrano[4,3-b]pyrroles.·A solution of the 3-(dimethylhydrazonoethylidene)thiochroman-4-one 8 (5 mmol) and sodium dithionite (25 mmol) in ethanol (20 cm3) and water (10 cm3) was refluxed for 2 h.The resulting colourless solution was diluted with water (150 cm3) and extracted with ethyl acetate (3Å50 cm3). The combined organic extracts were washed with water (2Å50 cm3), dried (Na2SO4) and evaporated to afford a pale yellow oil which crystallised upon cooling to give the crude pyrrole derivative which was purified by recrystallisation. 4,4-Dimethyl- 4H-[1]benzothiopyrano[4,3-b]pyrrole 9 (R=H) (55%) was obtained as colourless crystals from n-hexane–ethyl acetate, mp 146–147 °C; dH 1.67 (6 H, s, 4-Me), 6.22 (1 H, t, J 2.6, 3-H), 6.84 (1 H, t, J 2.7, 2-H2 H, m, 7-H and 8-H), 7.29 (1 H, dd, J 7.6, 1.3, 6-H), 7.38 (1 H, dd, J 7.5, 1.2, 9-H), 8.41 (1 H, m, N-H); dH (CDCl3+D2O) 6.17 (1 H, d, J 2.7, 3-H), 6.80 (1 H, d, J 2.7, 2-H) and absence of N-H signal (Found: C, 72.7; H, 6.1; N, 6.4; S, 14.8.C13H13NS requires C, 72.5; H, 6.1; N, 6.5; S, 14.9%). 4,4,8-Trimethyl- 4H-[1]benzothiopyrano[4,3-b]pyrrole 9 (R=8-Me) (46%) was obtained as colourless crystals from n-hexane–ethyl acetate, mp 151–152 °C; dH 1.61 (6 H, s, 4-Me), 2.34 (3 H, s, 8-Me), 6.16 (1 H, t, J 2.6, 3-H), 6.79 (1 H, t, J 2.8, 2-H), 6.88 (1 H, dd, J 7.9, 1.3, 7-H), 7.08 (1 H, d, J 1.2, 9-H), 7.23 (1 H, d, J 8.0, 6-H), 8.35 (1 H, bs, N-H). dH (CDCl3+D2O) 6.15 (1 H, d, J 2.6, 3-H), 6.78 (1 H, d, J 2.6, 2-H) and absence of N-H signal (Found: C, 73.1; H, 6.6; N, 6.2; S, 14.2.C14H15NS requires C, 73.3; H, 6.6; N, 6.1; S, 14.0%). 4 , 4 - D i m e t h y l - 4 H - n a p h t h o [ 1 p, 2 p: 5 , 6 ] t h i o p y r a n o [ 4 , 3 - b ] p y r r o l e 9 (R=8,9-benzo) (62%) was a pale green solid which decomposed on attempted purification by recrystallisation or sublimation; dH 1.67 (6 H, s, 4-Me), 6.24 (1 H, m, 3-H), 6.96 (1 H, m, 2-H), 7.43–7.56 (3 H, m, Ar-H), 7.69–7.79 (1 H, m, Ar-H), 8.05–8.10 (1 H, m, Ar-H), 8.36–8.42 (1 H, m, Ar-H), 8.78 (1 H, bs, NH).Received, 8th November 1996; Accepted, 4th December 1996 Paper E/6/07607F References 1 Inst. Materia Medica, Chinese Acad. Med. Sci., Scientia Sinica, 1976, 295 (Engl. Edn., 1977, 20, 106; Chem. Abstr., 1977, 87, 98585g). 2 X.-T. Liang, X.-D. Xsu, Z.-P. Zhang, H.-E. Gu and W.-X. Wang, Acta Chimica Sinica, 1976, 34, 129; X.-J. Xu, M.-C. Shao, Z.-E. Zhang, G.-B. Li, G.-D. Zhou and Y.-Q.Tang, Kexue Tongbao, 1980, 8, 350. 3 A. P. Kozikowski, M. N. Greco and J. P. Springer, J. Am. Chem. Soc., 1982, 104, 7622; M. J. Dickens, T. J. Mowlem, D. A. Widdowson, A. M. Z. Slawin and D. J. Williams, J. Chem. Soc., Perkin Trans. 1, 1992, 323; J. Y. L. Chung, R. A. Reamer and P. J. Reider, Tetrahedron Lett., 1992, 4717; H. Ishibashi, T. Tabata, K. Hanaoka, H. Iriyama, S. Akamatsu and M. Ikeda, Tetrahedron Lett., 1993, 489. 4 J. H. Hutchinson, E. J. McEachern, J.Scheigetz, D. Macdonald and M. Th�erien, Tetrahedron Lett., 1992, 4713. 5 M. Murase, N. Nishino, N. Nara, Y. Nakanishi and S. Tobinaga, Heterocycles, 1994, 37, 725; T. Saito, T. Shizuta, H. Kikuchi, J. Nakagawa, K. Hirotsu, H. Ohmura and S. Motoki, Synthesis, 1994, 727. 6 N. Ishizuka, J. Chem. Soc., Perkin Trans. 1, 1990, 813. 7 J. Mispelter, A. Croisy, P. Jacquignon, A. Ricci, C. Rossi and F. Schiaffela, Tetrahedron, 1977, 33, 2383. 8 T. E. Young and P. H. Scott, J. Org. Chem., 1965, 30, 3613; N. P. Buu-Hoi, A. Martani, A. Croisy, P. Jacquignon and F. P�erin, J. Chem. Soc. C, 1966, 1787; T. E. Young, B. Pa and P. H. Scott, US Pat. 3,388,133, 1968; A. Croisy, P. Jacquignon and A. Fravolini, J. Heterocycl. Chem., 1974, 11, 113; L. N. Borisova and T. A. Kartashova, Chem. Heterocycl. Compd. (Engl. Transl.), 1979, 15, 162; G. Kolenz, R. Theuer, W. Ott, K. Peters, E.-M. Peters and H. G. von Schnering, Heterocycles, 1988, 27, 479. 9 C. D. Gabbutt, J. D. Hepworth and B. M. Heron, J. Chem. Soc., Perkin Trans. 1, 1992, 2603; Tetrahedron, 1994, 50, 7685; 1995, 51, 13 277. 10 F. Eiden and E. Baumann, Arch. Pharm. (Weinheim, Ger.), 1983, 316, 897. 11 Th. Severin and H. Poelhmann, Chem. Ber., 1977, 110, 491. 12 A. Zinoune, J.-J. Bourguignon and C.-G. Wermuth, Heterocycles, 1989, 28, 1077. 13 S. W. Schneller, Adv. Heterocycl. Chem., 1975, 18, 59; A. H. Ingall, in Comprehensive Heterocyclic Chemistry, ed. C. W. Rees and A. R. Katritzky, Pergamon, Oxford, 1984, vol. 3, p. 885. 14 Th. Severin, R. Adam and H. Lerche, Chem. Ber., 1975, 108, 1756. 15 S. E. Clayton, C. D. Gabbutt, J. D. Hepworth and B. M. Heron, Tetrahedron, 1993, 49, 939. J. CHEM. RESEARCH (S), 1997

ISSN:0308-2342    

DOI:10.1039/a607607f

出版商:RSC    

年代:1997

数据来源: RSC

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104 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 104–105† Diels–Alder Reactions of 2-(Isoquinolin-1-yl)-5-phenyl- 3H-pyrrole-3-carboxylic Esters with N-Methyl- and N-Phenyl-maleimides† Sandrine Perrin, Karin Monnier and B. Laude* Laboratoire de Chimie et Electrochimie Mol�eculaire, Universit�e de Franche-Comt�e, 16 Route de Graym, La Bouloie, 25030 Besançon, France The reaction between the title compounds produces [4+2] Diels–Alder cycloadducts; the stereochemistry of the reaction is deduced from 1H NMR data.As part of our research on the reactivity of the tetrafluoroborate salts of Reissert compounds,1 we have already described the preparation of 3H-pyrrole-3-carboxylic esters 4 by the reaction of the Reissert compound tetrafluoroborate salt 2 with suitably gem-disubstituted a,b-ethylenic esters 3.2 When R3\H, prolonged heating in toluene converts the 3H-pyrrole 4 into the isomeric 1H-pyrrole 5 via a [1,5] sigmatropic rearrangement2 (Scheme 1).Since Diels–Alder reactions, in which the azole functions as an azadiene, have been observed either directly from 3H-pyrroles3 or from 2H-pyrroles via a [1,5] sigmatropic rearrangement to 3H-pyrroles,3–6 it was of interest to study reactions of the 3H-pyrroles derivatives 4 with some dienophiles. 7 In preliminary studies, the 3H-pyrrole 4a was treated with a variety of dienophiles in toluenic solutions at various temperatures (20–110 °C). Dimethyl acetylenedicarboxylate and methyl esters of propiolic, acrylic, fumaric and maleic acids gave complex mixtures in which the 1H-pyrrole 5a was the major component.N-Methyl- and N-phenyl-maleimides proved to be the most useful dienophiles for reactions with the 3H-pyrrole derivatives 4. 3H-Pyrroles 4 in toluene under reflux gave moderate to good yields of stable 1:1 adducts 6 (Scheme 2). Physical, analytical, IR (vC�O) and 1H and 13C NMR data for the adducts are given in Tables 1 and 2. 1H NMR data allowed the diastereochemistry of the cycloadducts 6 to be assigned.According to the literature,8,9 the exo oriented H-5 gives a signal in the form of a doublet of doublets owing to two vicinal couplings 3J4,5 4.3–4.6 Hz (R3=H) and 3J5,6 7.2–7.6 Hz whereas an appropriate endo oriented H-5 proton would give only a doublet, since one of the two vicinal proton couplings (3J4,5) would be close to zero. This endo configuration is also the stereochemistry described by Sammes et al.3 for the Diels–Alder adducts of other 3H-pyrroles with N-phenylmaleimide.In order to determine the diastereochemistry of the approach between the two reactants towards the ester group of the azadienic 3H-pyrroles 4, NOE difference experiments were carried out with the cycloadducts 6. The observed enhancements are examplified in the case of the cycloadduct 6af (Fig. 1). These observations may be extended to all cycloadducts 6 and lead to the choice of the endo–anti approach of the maleimide group to the ester group of the azadienic 2Hpyrroles 4. Thus, the cycloaddition is diastereoselective and the cycloadducts 6 are obtained with simultaneous control of the relative stereochemistry of five chiral centres.Experimental All mps are uncorrected. IR spectra (KBr) were recorded on a Bio-Rad FTS spectrophotometer. 1H and 13C NMR spectra were recorded on a Bruker-Spectrospin AC 200 spectrometer in CDCl3. *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Scheme 1 Scheme 2 Fig. 1 NOE enhancements for the cycloadduct 6afJ. CHEM. RESEARCH (S), 1997 105 Table 1 Physical and analytical data for 3H-pyrrole Diels–Alder adducts 6 Analysis (%) Reaction IR Yield Mp time (vC�O)/ Found (required) Adduct R1 R2 R3 R (%) T/°C) (t/h) cmµ1 C H N 6af (C32H25N3O4) Me Me H Ph 53 288 20 1713 1773 74.55 (74.37 4.89 4.86 8.15 7.99) 6ag (C27H23N3O4) Me Me H Me 64 187 8 1700 1710 71.51 (71.67 5.11 5.22 9.27 9.07) 1773 6bf (C34H27N3O6) Me CH2CO2Me H Ph 26 270 24 1718 1736 71.19 (71.23 4.74 4.91 7.33 7.27) 1758 6bg (C29H25N3O6) Me CH2CO2Me H Me 47 208 8 1702 1736 68.09 (67.98 4.93 4.96 8.21 8.32) 6cf (C33H27N3O4) Me Me Me Ph 16 248 24 1715 1770 74.85 (74.77 5.14 5.22 7.93 7.86) 6cg C28H25N3O4) Me Me Me Me 28 223 8 1700 1735 71.93 (72.07 5.39 5.28 8.99 8.92) 1769 6df (C33H23N3O4) ·CH2CH2· H Ph 46 312 3 1710 1764 74.85 (74.78 4.51 4.62 8.18 8.12) 6dg (C27H21N3O4) ·CH2CH2· H Me 49 293 3 1691 1764 71.84 (71.93 4.67 4.82 9.31 9.17) 6ef (C33H25N3O4) ·CH2CH2CH2· H Ph 40 263 16 1709 1774 75.13 (75.27 4.78 4.69 7.96 7.89) Table 2 1H NMR data (d ppm/CDCl3; J in Hz) for 3H-pyrrole Diels–Alder adducts 6 Adduct R1 R2 R3 H5 H6 R Aromatic protons 6af 2.97 (s, 3 H), 1.48 (s, 3 H) 4.53 (d, 1 H) 3.80 (dd, 1 H) 5.57 (d, 1 H) 6.55–6.65 (m, 2 H, ar.) 7.10–8.95 (m, 14 H, ar.) J4,5 4.7; J5,6 7.6 6ag 2.95 (s, 3 H) 1.43 (s, 3 H) 4.41 (d, 1 H) 3.64 (dd, 1 H) 5.40 (d, 1 H) 2.58 (s, 3 H) 7.40–8.85 (m, 11 H, ar.) J4,5 4.6; J5,6 7.9 6bf 2.99 (s, 3 H) 2.95 (AB syst., 2 H) JAB 17.4 4.82 (d, 1 H) 3.79 (dd, 1 H) 5.57 (d, 1 H) 6.55–6.65 (m, 2 H, ar.) 7.10–8.85 (m, 14 H, ar.) 3.68 (s, 3 H) J4,5 4.3; J5,6 7.6 6bg 2.97 (s, 3 H) 2.90 (AB syst., 2 H) JAB 17.4 4.70 (d, 1 H) 3.62 (dd, 1 H) 5.39 (d, 1 H) 2.58 (s, 3 H) 7.40–8.75 (m, 11 H, ar.) 3.67 (s, 3 H) J4,5 4.3; J5,6 7.4 6cf 2.90 (s, 3 H) 1.33 (s, 3 H) 2.01 (s, 3 H) 3.42 (d, 1 H) 5.56 (d, 1 H) 6.74–6.80 (m, 2 H, ar.) 7.15–8.95 (m, 14 H, ar.) J5,6 7.7 6cg 2.88 (s, 3 H) 1.29 (s, 3 H) 1.93 (s, 3 H) 3.26 (d, 1 H) 5.39 (d, 1 H) 2.69 (s, 3 H) 7.40–8.82 (m, 11 H, ar.) J5,6 7.5 6df 4.11 (m, 1 H) 3.83 (m, 1 H) 2.12 (t, 2 H) 4.40 (d, 1 H) 4.71 (dd, 1 H) 4.57 (d, 1 H) 6.65–6.75 (m, 2 H, ar.) 7.10–9.60 (m, 14 H, ar.) J4,5 4.6; J5,6 7.5 6dg 3.91 (t, 1 H) 2.48 (m, 1 H) 2.70 (m., 2 H) 4.28 (d,. 1 H) 3.58 (dd, 1 H) 5.50 (d, 1 H) 2.60 (s., 3 H) 7.45–8.95 (m, 11 H, ar.) J4,5 4.4; J5,6 7.5 6ef 3.95 (m, 1 H) 4.30 (m, 1 H) 1.50–1.90 (m, 4 H) 4.45 (d, 1 H) 3.68 (dd, 1 H) 5.71 (d, 1 H) 6.65–6.75 (m, 2 H, ar.) 7.20–9.55 (m, 14 H, ar.) J4,5 4.5; J5,6 7.56 Analytical data were performed by the CNRS Vernaison (France). 3H-Pyrroles 4 were obtained by literature methods.2 Preparation of Cycloadducts 6.·General procedure. A solution of 3H-pyrrole 4 (2 mmol) and N-methyl- or N-phenyl-maleimide (2.2 mmol) toluene (20 ml) was heated under reflux for an appropriate time (Table 1).The reaction mixture was then left at room temperature for 12 h. In the case of 6df, dg and ef, a small quantity of the rearranged 1H-pyrrole 5 crystallised. After filtration, the solution was evaporated and the obtained solid recrystallised from ethanol. Received, 8th November 1996; Accepted, 25th November 1996 Paper E/6/07614I References 1 D. Adnani, G. Schmitt, K. Monnier, B. Laude, M. M. Kubicki and M. Jannin, J. Chem. Res., 1996, (S) 74; (M) 0534 and references cited therein. 2 S. Perrin, K. Monnier and B. Laude, Bull. Soc. Chim. Belg., 1996, 105, 777. 3 K. H. Lui, T. F. Lai and M. P. Sammes, J. Chem. Res., 1989, (S) 244; (M) 1759. 4 A. Edda�ýf, A. Laurent, P. Mison and N. Pelissier, Tetrahedron Lett., 1984, 26, 2779; A. Edda�ýf, A. Laurent, P. Mison, N. Pelissier, P. A. Carrupt and P. Vogel, J. Org. Chem., 1987, 52, 5548. 5 P. H. Daniels, J. L. Wong, J. L. Atwood, L. G. Canada and R. D. Rogers, J. Org. Chem., 1979, 45, 435; B. K. Rammash, C. M. Gladstone and J. L. Wong, J. Org. Chem., 1981, 46, 3036. 6 M. E. Jung and J. J. Shapiro, J. Am. Chem. Soc., 1980, 102, 7862. 7 M. P. Sammes, personal communication. 8 T. Lakhlifi, A. Sedqui, B. Laude, Nguyen Dinh An and J. Vebrel, Can. J. Chem., 1991, 69, 1156. 9 H. Krawczyk and A. Gryff-Keller, J. Chem. Res., 1996, (S)

ISSN:0308-2342    

DOI:10.1039/a607614i

出版商:RSC    

年代:1997

数据来源: RSC

摘要:

Synthesis of Tetrahydrofurans and Pyrans via Palladium(0)-Mediated Cyclisation Christelle Fournier-Nguefack, Paul Lhoste and Denis Sinou* Laboratoire de Synthe© seAsyme� trique, associe� au CNRS, CPE Lyon Universite� ClaudeBernard Lyon I, 43, boulevard du11Novembre1918, 69622 Villeurbanne Ce� dex, France Palladium(0)-catalysed cyclisation of the appropriate hydroxy allylic carbonates inTHF allowed the formation of tetrahydrofurans and pyrans via a 5-exo-trig or a 6-exo-trig mechanism; preliminary experiments in the presence of palladium complexes associated with chiral ligands gave the expected substituted tetrahydrofurans with lowenantioselectivities.The regio- and stereo-selective synthesis of tetrahydrofurans and pyrans is an important challenge as they are key struc- tures of natural compounds such as ionophores. Following our work concerning the palladium(0) catalysed formation of the carbon±oxygen bond,29±35 we report a palladium(0) based cyclisation of an appropriate hydroxy allylic carbon- ate leading to substituted tetrahydrofurans and pyrans.Condensation of the lithio derivative of protected pent-1- yn-5-ol 2 with various aldehydes (Scheme 1) gave the prop- 2-ynylic alcohols 3 in good yields whose hydrogenation with hydrogen in the presence of Lindlar palladium led to the (Z) allylic alcohols 4. Reaction of alcohols 4 with methyl chloroformate in the presence of pyridine and DMAP gave the expected protected allylic carbonates 5.The desired hydroxy allylic carbonates 6 were obtained by deprotection of the hydroxy function of 5. When these compounds 6 were treated with a catalytic amount of palladium(0) associated with 1,4-bis(diphenylphosphino)butane in THF at 50 8C, the corresponding unsaturated tetrahydrofurans 11 were obtained in good yields, via a 5-exo-trig mechanism. The use of hex-1-yn-6-ol instead of pent-1-yn-5-ol in this sequence led to the formation of the unsaturated tetrahydro- pyran 19 via the same mechanism (Scheme 2), although the use of but-1-yn-4-ol gave only dienes 17 and 18 resulting from b-elimination.Preliminary experiments concerning the cyclisation of the prochiral allylic carbonate 24 in the presence of palladium(0) associated with chiral ligands led to the expected unsaturated tetrahydrofuran 26, but with low enantioselectivities (Scheme 3). Techniques used: 1H and 13C NMR and chiral HPLC References: 38 Schemes: 9 Tables: 2 (yields for products of condensation, hydrogenation, methoxycarbonylation and deprotection; enantioselectivities in the cyclisation reaction) Received, 31st July 1997; Accepted, 30th October 1997 Paper F/7/07902H References cited in this synopsis 29 R.Lakhmiri, P. Lhoste and D. Sinou, Tetrahedron Lett., 1989, 30, 4669. 30 R. Lakhmiri, P. Lhoste, P. Boullanger and D. Sinou, J. Chem. Res. 1990, (S) 342; (M) 2301. 31 R. Lakhmiri, P. Lhoste and D. Sinou, Synth. Commun., 1990, 20, 1551. 32 C. Goux, P. Lhoste and D. Sinou, Synlett, 1992, 725. 33 R. Lakhmiri, P. Lhoste, B. Kryczka and D. Sinou, J. Carbohydr. Chem., 1993, 12, 223. 34 D. Sinou, I. Frappa, P. Lhoste, S. Porwanski and B. Kryczka, Tetrahedron Lett., 1995, 36, 1251. 35 C. Goux, M. Massacret, P. Lhoste and D. Sinou, Organometallics, 1995, 14, 4585. J. Chem. Research (S), 1998, 105 J. Chem. Research (M), 1998, 0614±0634 Scheme 1 Reagents and conditions: i, BuLi, RCHO,THF, DMPU, ¡40 8C then ¡10 8C; ii, H2, Lindlar Pd, MeOH, 25 8C; iii, ClCO2Me, C5H5N, DMAP, CH2Cl2, 25 8C; iv, Bu4NF.3H2O,THF, 25 8C; v, Pd0^dppb,THF, 50 8C Scheme 2 Scheme 3 *To receive any correspondence. J. CHEM. RESEARCH (S),

ISSN:0308-2342    

DOI:10.1039/a707902h

出版商:RSC    

年代:1998

数据来源: RSC