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Technetium and rhenium oxo-complexes of new tetradentate ligands withN2S2and NS3donorsets |
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Dalton Transactions,
Volume 1,
Issue 8,
1997,
Page 1403-1410
Colin M. Archer,
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摘要:
DALTON J. Chem. Soc. Dalton Trans. 1997 Pages 1403–1410 1403 Technetium and rhenium oxo-complexes of new tetradentate ligands with N2S2 and NS3 donor sets † Colin M. Archer,b Jonathan R. Dilworth,a D. Vaughan GriYths,a Mohammad J. Al-Jeboori,a J. Duncan Kelly,b Canzhong Lu,a Mark J. Rossera and Yifan Zhenga a Department of Chemical and Biological Sciences University of Essex Wivenhoe Park Colchester Essex CO4 3SQ UK b Amersham International White Lion Road Amersham Bucks. HP7 9LL UK A series of new tetradentate nitrogen–sulfur donor proligands with amido or amino donor groups have been synthesized and their rhenium and technetium oxo-complexes prepared. The substitution pattern and length of the ligand backbone can be varied without affecting the co-ordination chemistry. The NS3H3 amido-proligands reacted rapidly with the technetium(V) precursor [TcOCl4]2 at reflux in methanol to give the technetium(IV) species [TcO(NS3)]2 in very high radiochemical purity (ca.100%) but these complexes decompose over a period of hours or days. They also reacted with the rhenium(V) precursors [ReO2(py)4]Cl (py = pyridine) or [ReOCl3(PPh3)2] at reflux in methanol but only in the presence of a base. Stable neutral rhenium(V) complexes of the type [ReO(NS3)] were formed and the crystal structures of two determined. A reduced amino version of the NS3H3 proligand gave an analogous [ReO(NS3)] complex and its crystal structure was determined. Technetium as the radioisotope 99mTc is the isotope of choice for many diagnostic nuclear medicine applications due to its virtually ideal characteristics.1 However it is only produced at very low concentrations and has a half-life of only about 6 h.Consequently the study of its co-ordination chemistry is diffi- cult. The long-lived isotope 99Tc can be safely handled in milligram quantities and is therefore generally used for chemical and structural studies. Rhenium is of interest not only because it forms many complexes which are directly analogous to those of technetium but also because the b-emitting radionuclide 188Re has potential therapeutic applications in nuclear medicine. Complexes of technetium as [TcO]31 with ligands possessing a tetradentate N2S2 donor set are well known.2 The stability and versatility of such complexes is demonstrated by the wide range which has been published. However the N2S2 ligands used to date have invariably featured both sulfur atoms as terminal thiol groups and both nitrogen atoms as part of the ligand backbone.If the nitrogen atoms are not derivatised i.e. they are secondary amines or amides then there are four labile protons. Only three of these should be removed to give a trianion which will form neutral complexes with the technetium core [Tc]] O]31. We have attempted to prepare complexes of 99Tc with hydrophilic N2S2 ligands of the general formula shown in which there is one terminal thiolate sulfur and one terminal carboxamide group. Variants with substituents capable of forming links to biomolecules were also prepared by derivatisation of the terminal carboxamide. These compounds have only three labile protons and it was hoped that they would readily form stable neutral complexes with a [Tc]] O]31 core.As has been reported in a previous communication,3 stable complexes were formed at the technetium-99m level and found to have very promising preliminary biodistribution characteristics. At the technetium- 99 level however we found it very difficult to form or isolate pure technetium-99 complexes with these compounds. While the reasons are not entirely clear it may be that the thioether and thiolate sulfurs are slightly better donors than the nitrogens for Tc in these complexes and so unstable 2 1 (ligand metal) complexes may form with each ligand bound only † Non-SI unit employed mmHg ª 133 Pa. through the sulfur atoms. Such complexes would be stable at the technetium-99m level where the ligand would be present in a large excess. The outcome of the complexation reaction between these compounds and technetium-99 precursors was very sensitive to the nature of the terminal N-substituent indicating that steric or small electronic factors affect the affinity of the proligand for [TcO]31.This is consistent with the amide nitrogen being relatively weakly bound. Kinetic studies with S-substituted N2S2 compounds have also suggested that it is the thiol groups of a polydentate ligand which are of primary importance in dictating the stability of a complex with Tc.4 Owing to these difficulties with this class of N2S2 potentially trianionic ligands we endeavoured to design dithiolates which would form neutral monooxotechnetium(V) complexes and be capable of derivatisation in a straightforward manner. It was reasoned that an NS3 ligand with two terminal thiolate donor atoms would meet these requirements.We were also interested to observe the effects of imposing an asymmetric co-ordination about the metal ion. We here report the synthesis of such a range of NS3 compounds of general formula shown in Scheme 2 and the results of our attempts to form complexes with both 99Tc and Re. While this work was in progress a patent was published which showed that a similar type of proligand prepared in analogous fashion could be effectively used at the technetium-99m level to conjugate a technetium-99m oxo-core to a peptide or peptide fragment.5 However it made no mention of the synthesis of complexes of 99Tc or Re or of proligands with longer carbon backbones. The synthesis of the ‘expanded’ NS3 proligand H3L2 from the seven-membered cyclic mercapto-thioester 2 also reported here is new.Attempts to prepare the corresponding H3L3 from the seven-membered 3 were not successful. S NH HN SH O COR 1404 J. Chem. Soc. Dalton Trans. 1997 Pages 1403–1410 Results and Discussion Synthesis of proligands and precursors The cyclic mercapto-thioesters 1–5 were synthesized according to the general method shown in Scheme 1 and the NS3H3 proligands according to Scheme 2. Although a derivative of the seven-membered cyclic mercapto-thioester 2 has been prepared previously,6 the method we have used is considerably more straightforward. Also the use of seven-membered rings in the synthesis of tetradentate nitrogen–sulfur donor pro-ligands with enlarged chelate rings (H3L2 and H3L3) is unprecedented. It is curious that while H3L2 was readily prepared from 2 H3L3 could not be prepared from the surprisingly unreactive 3.We also attempted to prepare expanded analogues of H3L4 by using the ethyl ester of homocysteine [HS(CH2)2CH(CO2Et)NH2] instead of that of cysteine [HSCH2CH(CO2Et)NH2] but were unable to find a suitable solvent in which the reagents were mutually soluble. Other variants of the proligands were prepared in a straightforward manner from the appropriate cyclic thioester and dithiol. The reduced proligand H3L10 was prepared by treatment of H3L1 with borane in tetrahydrofuran (thf ) under reflux. Scheme 1 S (CH2)n OC S CHR (CH2)m HS(CH2)n SH + ClCHR(CH2)mCOCl 1 m = 0 n = 2 R = H 2 m = 0 n = 3 R = H 3 m = 1 n = 2 R = H 4 m = 0 n = 2 R = Me 5 m = 0 n = 2 R = Ph Scheme 2 i reduction BH3 thf R = R1 = R2 = R3 = H m = 0 n = 2 only S (CH2)n OC S CHR (CH2)m SH (CH2)n S RCH (CH2)m C NH O CHR1 CR2R3 HS S NH HS SH + H2NCHR1CR2R3SH Ligand H3L1 H3L2 H3L3 H3L4 H3L5 H3L6 H3L7 H3L8 H3L9 H3L10 m 0 2 H H H H 0 3 H H H H 1 2 H H H H 0 2 H H H CO2Et 0 2 H H Me Me 0 2 H H H Me 0 2 H Me Me Me 0 2 H H H Ph 0 2 H Me Me Ph 0 2 H H H H R1 n R2 R3 R (i ) H3L10 Synthesis of rhenium complexes The common rhenium(V) precursors [ReOCl3(PPh3)2] and [ReO2(py)4]Cl (py = pyridine) both reacted with proligands H3L1 H3L2 and H3L4–H3L10 (H3L3 was not successfully prepared) to form the neutral complexes [ReO(Ln)].The reactions were carried out in methanol under reflux in the presence of sodium acetate and under a nitrogen atmosphere. No reaction occurred with the precursors in the absence of a base (sodium acetate).The choice of base and solvent were also important and no pure complexes could be isolated using triethylamine– methanol or –thf. Significantly in terms of their possible application for radiopharmaceuticals we have also been able to prepare the same [ReO(L)] complexes directly from perrhenate with the addition of citric acid (3-carboxy-3-hydroxypentane- 1,5-dioic acid) and SnCl2 as the reducing agent. In the absence of citric acid only intractable black solids were obtained. The HPLC of the reaction solutions immediately after the reflux for all precursors including perrhenate showed that although isolated yields were low a single product predominated and that the retention times were identical to those of the finally isolated products. Only in the cases where [ReOCl3(PPh3)2] was used as precursor a small variable amount (< 5%) of insoluble green solid was formed which was filtered off but not identified.Complexes of the asymmetric tetradentate ligands without substituents on the backbone exist in principle in two isomeric forms differing in the disposition of the Re]] O group. These are non-superimposable enantiomers. As expected only one isomer is observed in solution by NMR spectroscopy or HPLC which are unable to discriminate between the two forms. There are also possible isomers involving different conformations of the backbones which should occur for all of the complexes but are not apparently observed. The introduction of one or three substituents onto the backbone as in proligands H3L6–H3L9 results in two further possible isomers differing in the orientation of the substituent R or R9 with respect to the Re]] O group (syn and anti forms).However the presence of isomers in solution was observed by NMR spectroscopy and HPLC (comparable ratios with both techniques) only for complexes [ReO(L4)] [ReO(L7)] and [ReO(L9)]. The reasons for this are not entirely clear but it appears that the steric hindrance offered by the two methyl groups adjacent to a thiolate sulfur in the last two complexes above may prevent facile equilibration between the isomers. All the new rhenium complexes were fully characterised by elemental analysis IR FAB and 1H and 13C NMR spectroscopy. Where necessary full assignments of peaks in the 1H and 13C NMR spectra were made using two-dimensional correlated spectroscopy (COSY). In the case of [ReO(L1)] [ReO(L2)] and [ReO(L10)] crystals suitable for X-ray diffraction analysis were grown from dichloromethane–isopropyl alcohol.Crystal structures of [ReO(L1)] [ReO(L2)] and [ReO(L10)] The ORTEP views of the three structures appear in Figs. 1–3 details of the determinations in Table 1 and selected bond lengths and angles in Table 2. The three structures are generally similar and the increase in backbone segment length (L2 complex) and reduction of the carboxamide group (L10 complex) cause relatively little variation in the bond distances and angles. The overall structures can be described as square pyramidal with the oxygen at the apical position and the basal plane comprising S(1) S(2) N and S(3). The chief effect of introducing the trimethylene backbone in the complex of L2 is to contract the O]Re]N(1) angle with a concomitant increase in the N]Re]S(1) angle; other parameters are remarkably similar.A least-squares plane analysis for N Re C(5) or C(4) and C(5) or C(6) shows that the nitrogen atoms are virtually planar in the amide complexes whereas in the reduced species the nitrogen is more pyramidal with the nitrogen an average (over the two molecules in the unit cell) of 0.26 Å above the plane. J. Chem. Soc. Dalton Trans. 1997 Pages 1403–1410 1405 Table 1 Details of crystal structure determinations [ReO(L1)] [ReO(L2)] [ReO(L10)] Empirical formula Formula weight Scan rate/ 8 min21 Crystal system Space group a/Å b/Å c/Å U/Å3 Z Dc/Mg m23 m/mm21 F(000) Crystal size/mm colour q Range for data collection/8 h,k,l Ranges Reflections collected Independent reflections Standard decay correction (%) Weighting scheme w21 Data restraints parameters Goodness of fit on F2 R1 wR2 (all data) Largest difference peak and hole/e Å23 Maximum shift/e.s.d.C6H10NO2ReS3 410.53 1–7 (in w) Orthorhombic Pbca 10.688(3) 13.785(5) 14.204(4) 2092.8(10) 8 2.606 12.178 1536 0.42 × 0.42 × 0.42 dark red 2.81–24.95 212 to 0 216 to 0 216 to 0 1842 1842 1.5 [s2(Fo)2 1 (0.0672P)2 1 7.6221P] 1842 0 159 1.070 0.0356 0.0960 2.330 21.283 0.255 C7H12NO2ReS3 424.56 Orthorhombic Pna21 10.706(4) 14.866(10) 7.030(5) 1118.9(12) 4 2.520 11.393 800 0.28 × 0.07 × 0.07 dark brown 2.34–25.03 211 to 11 216 to 16 25 to 7 4481 1598 (Rint = 0.1447) [s2(Fo)2 1 (0.0839P)2] 1543 7 128 1.096 0.0645 0.1665 4.039 22.383 20.001 C6H12NOReS3 396.54 1–7 (in w) Monoclinic Pn 11.495(3) 7.1182(2) 13.020(4) 1058.2(5) 4 2.489 12.030 744 0.23 × 0.12 × 0.12 dark brown 2.24–24.98 213 to 13 0–8 0–15 1946 1946 2.4 [s2(Fo)2 1 (0.0455P)2 1 3.4269P] 1946 44 215 1.032 0.0283 0.0665 1.541 21.241 0.063 Synthesis of technetium-99 complexes The proligand H3L1 (ca.2 equivalents) reacted rapidly with [NBu4][TcOCl4] in methanol at reflux to produce a pure single technetium species (as shown by HPLC b and UV detection and by analytical TLC) which remained in solution and an insoluble precipitate. The HPLC measurements on the technetium complexes were made using a mixed-solvent system and are not directly comparable to the data reported elsewhere in the paper for the rhenium complexes nor to the data in ref. 5 for 99mTc. The technetium complex of L1 was easily isolated as an amber coloured oil but decomposed over a period of days.A peak at 948 cm21 in the IR spectrum of the freshly prepared product was assigned to a Tc]] O stretch although it was weaker than would normally be expected for this vibration. No peaks which could be assigned to n(NH) or n(SH) were seen. The 1H and 13C NMR spectra showed only peaks which could be attributed to NBu4 1 and no peaks for the bound ligand were seen. This indicates that the product is both NMR silent and Table 2 Comparison of selected bond lengths (Å) and angles (8) [ReO(L10)] [ReO(L1)] [ReO(L2)] Molecule 1 Molecule 2 Re]O Re]N Re]S(3) Re]S(1) Re]S(2) C(3)]O C]N 1.686(5) 2.003(6) 2.293(2) 2.281(2) 2.368(2) 1.217(10) 1.378(10) [C(4)]N] 1.703(9) 2.015(11) 2.294(4) 2.303(4) 2.406(4) 1.27(2) 1.34(2) [C(5)]N] 1.689(11) 2.09(2) 2.282(7) 2.303(5) 2.330(6) 1.44(2) [C(4)]N] 1.72(2) 1.99(2) 2.276(5) 2.309(8) 2.385(5) 1.47(2) [C(04)]N] O]Re]N O]Re]S(1) N]Re]S(1) O]Re]S(3) N]Re]S(3) S(1)]Re]S(3) O]Re]S(2) N]Re]S(2) S(1)]Re]S(2) S(2)]Re]S(3) 119.8(3) 114.5(2) 125.5(2) 106.6(2) 81.9(2) 86.13(7) 100.3(2) 82.3(2) 85.27(7) 152.87(7) 114.8(5) 111.9(3) 133.3(3) 105.4(4) 82.8(3) 85.8(3) 102.3(3) 81.2(3) 88.5(2) 151.84(14) 118.8(7) 111.0(4) 137.0(5) 109.2(5) 82.9(5) 87.0(2) 101.7(5) 81.3(4) 86.4(2) 148.7(2) 112.0(8) 114.3(6) 133.5(5) 110.4(5) 82.0(4) 86.1(2) 100.3(5) 82.0(4) 85.9(2) 148.9(2) anionic both of which can be understood if we formulate the product as a paramagnetic technetium(IV) species [NBu4]- [TcIVO(L1)].Further characterisation was not possible because of decomposition. The complex has an HPLC retention time of 9 min (aqueous NaO2CMe–thf solvent gradient) and over a period of several hours decomposes to a secondary product having a retention time of 6 min.We have some qualitative HPLC evidence which indicates that this step is at least partially reversed when a base (NaOMe) is added and the oxotechnetium(IV) complex is reformed. The secondary product in turn decomposes to a species with a retention time of about 2 min similar to that of [NBu4][TcO4]. This decomposition product has been isolated by column chromatography and an IR spectrum contained a very strong peak at 895 cm21. This is attributed to the Tc]O stretching vibration of [TcO4]2 and indicates that the complex has decomposed to pertechnetate which necessarily involves oxidation of the technetium core. As yet we have been unable to isolate the initial decomposition product having a retention time of 6 min.Direct comparison of our results with those obtained in the technetium-99m work of ref. 5 is not possible as different HPLC systems were used. Fig. 1 An ORTEP7 representation of the structure of [ReO(L1)] showing the atom labelling scheme 1406 J. Chem. Soc. Dalton Trans. 1997 Pages 1403–1410 When the reaction between [TcOCl4]2 and H3L1 is carried out in the presence of a base (NaO2CMe) the same technetium species is formed. The formation of the latter occurs in the absence of base in contrast to the rhenium complexes. This is probably due to the greater substitutional lability of the technetium core. A similar product was formed from the reaction between [NBu4][TcOCl4] and proligand H3L4.In this case the CO2Et substituent acts as a model for the precursor of a complex in which the Tc]NS3 moiety is coupled to a small biologically active molecule via an activated ester group. In all other respects (1H 13C NMR HPLC retention time) the products were very similar. This product has a HPLC retention time of 8.5 min and also decomposes to species having retention times of 5.5 and 2 min. We have not examined this decomposition. With proligand H3L2 the reaction appeared to proceed in an analogous manner. Analysis of the crude product by HPLC indicated that the major product was a technetium species with retention time of 9 min but there were two other relatively minor technetium species having retention times of 2 and 6 min. An attempt to purify the product was made by column chromatography but decomposition on the column prevented the isolation of pure product.Conclusion We have prepared a variety of [ReO(L)] complexes where L is triply deprotonated which have been fully characterised. Technetium-99 complexes with the same ligands have been prepared in high radiochemical purity which appear to contain [TcO(Ln)]2 but their instability has prevented complete characterisation. We have isolated and characterised the final decomposition product of the technetium complex with ligand H3L1 Fig. 2 An ORTEP representation of the structure of [ReO(L2)] showing the atom labelling scheme Fig. 3 An ORTEP representation of one of the two non-equivalent molecules of [ReO(L10)] showing the atom labelling scheme and found that it is [NBu4][TcO4]. The HPLC analysis indicates that this decomposition is at least a two-step process with the first step reversed by the addition of sodium methoxide suggesting that protonation is involved.The available data therefore indicate that the complexes of Re and Tc are not directly analogous. We propose that the [Tc]] O]31 core is reduced by the ligand whereas the less easily reduced [Re]] O]31 core remains as ReV. The decomposition of the technetium complexes is slow compared to the half-life of 99mTc and so is likely to be unimportant in radiopharmaceutical terms. The results of labelling the series of ligands with the technetium-99m isotope will be reported elsewhere. We envisage using NS3 compounds similar to H3L4 in which the ethyl ester group will be replaced by more biologically relevant molecules such as small polypeptides allowing us to target particular receptor sites.Experimental CAUTION technetium-99 is a low-energy b emitter [292 keV (ca. 4.67 × 10214 J t2� 1 = 2.14 × 105 years). Normal radiation safety procedures were followed at all times. All manipulations of solutions and solids were performed in an efficient fumehood to prevent contamination and inadvertent inhalation. When handled in milligram quantities these compounds do not present a serious health hazard since common laboratory glassware provides adequate shielding. Bremsstrahlung radiation is not a significant problem due to the low energy of the b-particle emission. Potassium pertechnetate was kindly donated by Amersham International plc and used as received. All other reagents were obtained from Aldrich Chemical Co.and used as received. The salt [NBu4][TcOCl4] was prepared from K[TcO4] according to standard methods.8 [ReOCl4(PPh3)2] and [ReO2(py)4]Cl from NH4ReO4.9 Infrared spectra were recorded as KBr discs or thin films on salt plates using a Perkin-Elmer 1600 series FTIR spectrometer NMR spectra on a JEOL EX 270 Fouriertransform spectrometer at 270 (1H) or 67.5 MHz (13C) and mass spectra using an MS 50 instrument. Elemental analyses were performed using a Carlo-Elba elemental analyser. For the technetium complexes HPLC was carried out using a Hamilton PRP-1 reversed-phase column and a solvent flow of 1.5 cm3 min21 with a 15 min 50 mmol aqueous sodium acetate–thf solvent gradient; UV (285 nm) and b (custom-built) detectors were used to monitor the column eluent. For the rhenium complexes HPLC employed a Gilson S5ODS1 (octadecylsilane) column with an isocratic system and flow rate 1 cm3 min21 with CH2Cl2 elution and UV (254 nm) detection.Preparations 2-Oxo-1,4-dithiacyclohexane 1. A three-necked roundbottomed flask (1 l) was equipped with a pressure-equalised dropping funnel (500 cm3) a thermometer and a nitrogen inlet. The flask was charged with dichloromethane (250 cm3) ethane- 1,2-dithiol (16.6 g 0.17 mol) and triethylamine (49.3 cm3 0.3 mol) under a nitrogen atmosphere. The dropping funnel was charged with chloroacetyl chloride (20.0 g 0.17 mol) in dichloromethane (150 cm3) also under a nitrogen atmosphere. The contents of the flask were cooled to about 2 10 8C in an ice–acetone bath and the solution of chloroacetyl chloride solution added dropwise while stirring over 1.5 h during which time a precipitate of triethylamine hydrochloride formed.The mixture was allowed to warm to room temperature and stirred for 2 h. The precipitate was filtered off and the organic layer washed with water (2 × 75 cm3) and dried over MgSO4. The drying agent was filtered off and the solvent evaporated at reduced pressure. The residue was purified by distillation under vacuum to give a clear colourless oil. Yield 13 g (60%). B.p. 105–108 8C 1 mmHg (lit.,10 b.p. 92–93 8C 0.7 mmHg). IR (KBr J. Chem. Soc. Dalton Trans. 1997 Pages 1403–1410 1407 disc) 1656 cm21 [n(C]] O)]. NMR (CDCl3) 1H d 3.44 (2 H s C3H) 3.41–3.37 (2 H t J = 5.7 6.5 CH2) 3.16–3.11 (2 H t J = 6.5 5.7 Hz CH2); 13C d 196.94 (C2) 35.40 (C3) 31.18 (C5) and 25.88 (C6). Electron impact (EI) mass spectrum m/z = 134 (M1).2-Oxo-1,4-dithiacycloheptane 2. The method used was analogous to that for compound 1 but with propane-1,3-dithiol (15.0 g 0.138 mmol) in place of ethane-1,2-dithiol. The quantities of the other reagents were adjusted accordingly and an identical work-up procedure gave a pale yellow oil. Spectrocopic analysis of the product indicated that it was contaminated with small amounts of triethylamine hydrochloride and starting material and repeated distillations of the oil did not improve the purity. The impure compound was successfully used in the synthesis of proligand H3L2 without further purifi- cation. Alternatively the crude produce (undistilled) could be used without purification. Yield 3.5 g (17%). IR (KBr disc) 1681 cm21 [n(C]] O)]. NMR (CDCl3) 1H d 3.41 (2 H s C3H) 3.10–2.94 (2 H m CH2) 2.77–2.55 (2 H m CH2) and 1.99– 1.84 (2 H m CH2); 13C d 196.29 (C2) 42.16 (C3) 32.75 (C5) 31.47 (C7) and 24.50 (C6).EI mass spectrum m/z = 73 [M 2 SCHOCH2]1; 106 [M 2 CHOCH2]1; and 148 M1. 5-Oxo-1,4-dithiacycloheptane 3. The method used was analogous to that procedure given for compound 1 but with 3- chloropropanoyl chloride (15.0 g 0.138 mmol) in place of chloroacetyl chloride. The quantities of the other reagents were adjusted accordingly and an identical work-up procedure gave a white solid. Yield 12.6 g (62%). IR (KBr disc) 1669 cm [n(C]] O)]. NMR (CDCl3) 1H d 3.11 (2 H t J = 7.5 6 Hz C3H) 2.93 (2 H s C6H) 2.90 (2 H s C7H) and 2.75 (2 H s C4H); 13C d 196.7 (C2) 44.1 (C3) 32.2 (C4) 29.0 (C6) and 27.2 (C7). EI mass spectrum m/z = 148 M1.3-Methyl-2-oxo-1,4-dithiacyclohexane 4. The method used was analogous to that for compound 1 but with 2-chloropropanoyl chloride (20.0 g 0.157 mol) in place of chloroacetyl chloride. The quantities of the other reagents were adjusted accordingly and an identical work-up procedure gave a pale yellow oil. The crude product could be used without further purification. Yield 12 g (52%). IR (KBr disc) 1666 cm21 [n(C]] O)]. NMR (CDCl3) 1H d 3.84–3.79 (1 H q 2J = 6.45 6.85 3J = 13.3 C3H) 2.89–2.77 (4 H m C5,6 and 1.38 (3 H d J = 6.9 Hz CH3); 13C d 199.28 (C2) 49.89 (C3) 31.30 (C5) 27.76 (C6) and 13.69 (CMe). EI mass spectrum m/z = 105 [M 2 CH2CH2]1; and 148 M1. 2-Oxo-3-phenyl-1,4-dithiacyclohexane 5. The method used was analogous to that given for compound 1 but with (1)- chloro(phenyl)acetyl chloride (20.0 g 0.105 mol) in place of chloroacetyl chloride.The quantities of the other reagents were adjusted accordingly and an identical work-up procedure gave a white solid. The compound could be used without further purification. Yield 13 g (59%). IR (KBr disc) 1654 cm21 [n(C]] O)]. NMR (CDCl3) 1H d 7.37–7.30 (5 H m aryl) 4.81 (1 H s C3H) and 3.42–3.01 (4 H m C5,6H); 13C d 196.91 (C2) 128.88 (Ph) 128.82 (Ph) 128.69 (Ph) 128.40 (Ph) 126.53 (Ph) 51.87 (C3) 31.16 (C5) and 27.71 (C6). EI mass spectrum m/z = 105 [M 2 CH2CH2Ph]1; 172 [M 2 CH2CH2]1; and 210 M1. Proligand H3L1. 2-Oxo-1,4-dithiacyclohexane (1.5 g 11 mmol) was dissolved in dry degassed dichloromethane (50 cm3) under a nitrogen atmosphere. A solution of 2-aminoethanethiol hydrochloride (1.3 g 11 mmol) and triethylamine (1.6 cm3 11 mmol) in dry degassed dichloromethane (100 cm3) was added dropwise.The mixture was allowed to stir for 12 h under a nitrogen atmosphere before washing with 2% aqueous citric acid (2 × 70 cm3) and then water (2 × 70 cm3). The organic layer was dried over MgSO4 and then filtered. Solvent was removed under reduced pressure and the residue dried under vacuum to give the required compound as a clear colourless oil. Yield 1.4 g (60%). IR (KBr disc) 3290 [n(NH)] 2544 [n(SH)] and 1649 cm21 [n(C]] O)]. NMR [(CD3)2SO] 1H d 8.20 (1 H br s NH) 3.25–3.18 (2 H q 2J = 6 3J = 12 Hz C5H) 3.13 (2 H s C3H) 2.80–2.70 (4 H m) 2.67–2.49 (3 H m) and 2.35 (1 H br SH); 13C d 169.0 (C4) 42.15 (C5) 35.52 (C3) 34.0 (C2) 23.68 (C1) and 23.31 (C6). EI mass spectrum m/z = 119 [M 2 SCH2CH2S]1; 151 [M 2 CH2CH2S]1; and 211 M1.Proligand H3L2. The method used was similar to that for H3L1 but with compound 2 (1.0 g 6.75 mmol) in place of 1. The quantities of the other reagents were adjusted accordingly. An identical work-up procedure gave the required compound as a pale yellow oil. Yield 0.45 g (30%). IR (KBr disc) 3290 [n(NH)] 2547 [n(SH)] and 1650 cm21 [n(C]] O)]. NMR (CDCl3) 1H d 7.36 (1 H br s NH) 3.51–3.42 (2 H q 2J = 6 3J = 12 C6H) 3.24 (2 H s C4H) 2.76–2.59 (6 H m C1,3,7H) 1.90 (2 H t J = 7 C2H) 1.49–1.42 (1 H t J = 8 SH) and 1.44–1.38 (1 H t J = 8 Hz SH); 13C d 168.95 (C5) 42.48 (C6) 35.89 (C4) 32.62 (C3) 31.14 (C2) 24.50 (C1) and 23.25 (C7). EI mass spectrum m/z = 106 [M 2 CH2CONHCH2CH2SH]1; 163 [M 2 HSCH2CH2]1; and 224 M1. Proligand H3L3. Using a method similar to that for H3L1 but with compound 3 in place of 1 only unchanged starting materials could be recovered from the reaction.The reasons for this are not certain but may be related to lower ring strain and therefore reduced reactivity of 3. Proligand H3L4. The method used was similar to that for H3L1 but the ethyl ester of L-cysteine hydrochloride was employed in place of 2-aminoethanethiol. The quantities of the other reagents were adjusted accordingly. An identical work-up procedure gave the required compound as a clear colourless oil which solidified on standing overnight. Yield 1.8 g (58%) m.p. 37 8C (Found C 38.5; H 6.2; N 4.7. Calc. for C9H17NO3S3 C 38.2; H 6.1; N 4.9%). IR (KBr disc) 3290 [n(NH)] 2544 [n(SH)] 1735 [n(C]] O)] and 1632 cm21 [n(C]] O)]. NMR (CDCl3) 1H d 7.62 (1 H br d J = 7 NH) 4.88–4.82 (1 H m C5H) 4.35– 4.20 (2 H m) 3.31 (2 H s C3H) 3.13–3.01 (2 H m) 2.99–2.73 (4 H m) 1.73 (1 H t J = 8 SH) 1.44 (1 H t J = 9 SH) and 1.32 (3 H t J = 7 Hz C9H); 13C d 169.68 (C7) 168.00 (C4) 62.08 (C5) 53.69 (C8) 36.63 (C3) 35.63 (C2) 26.76 (C1) 24.20 (C6) and 14.21 (C9).EI mass spectrum m/z = 223 [M 2 HSCH2CH2]1; 250 [M 2 SH]1; and 283 M1. Proligand H3L5. The method used was similar to that for H3L1 but with 1-amino-2-methylpropane-2-thiol hydrochloride (1.62 g 0.11 mol) in place of 2-aminoethanethiol. The quantities of the other reagents were adjusted accordingly. An identical work-up procedure gave the required compound as a clear colourless oil. Yield 1.10 g (40%). IR (KBr disc) 3302 [n(NH)] 2543 [n(SH)] and 1649 cm21 [n(C]] O)]. NMR (CDCl3) 1H d 7.36 (1 H br NH) 3.37 (2 H d J = 6 C5H) 3.30 (2 H s C3H) 2.88–2.72 (4 H m C1,2H) 1.75 (2 H t J = 6.5 8 Hz SH) and 1.37 (6 H s C6A,6BH); 13C d 168.80 (C4) 52.30 (C5) 45.21 (C6) 36.74 (C3) 35.70 (C2) 29.97 (C6A,6B) and 24.16 (C1).EI mass spectrum m/z = 179 [M 2 CH2CH2SH]1; 206 [M 2 SH]1; and 240 M1. Proligand H3L6. The method used was similar to that for H3L1 but with compound 4 (1.5 g 0.01 mol) in place of 1. The quantities of the other reagents were adjusted accordingly and an identical work-up procedure gave the required compound as a clear colourless oil. Yield 1.2 g (53%). IR (KBr disc) 3298 [n(NH)] 2548 [n(SH)] and 1650 cm21 [n(C]] O)]. NMR (CDCl3) 1H d 7.15 (1 H br NH) 3.51–3.41 (3 H m C3,5H) 2.89–2.67 (6 H m C1,2,6H) 1.75–1.67 (1 H m SH) 1.49–1.47 1408 J. Chem. Soc. Dalton Trans.1997 Pages 1403–1410 (3 H d J = 7.2 C3AH) and 1.45–1.39 (1 H t J = 8.4 Hz SH); 13C d 172.59 (C4) 44.13 (C5) 42.47 (C3) 35.43 (C2) 24.53 (C1) 24.49 (C6) and 18.58 (C3A). EI mass spectrum m/z = 133 [M 2 HSCH2CH2]1; 192 [M 2 SH]1; and 225 M1. Proligand H3L7. The method used was similar to that for H3L6 but with 1-amino-2-methylpropane-2-thiol hydrochloride (0.97 g 6.8 mmol) in place of 2-aminoethanethiol. The quantities of the other reagents were adjusted accordingly. An identical work-up procedure gave the required compound as a colourless oil. Yield 0.7 g (40%). IR (KBr disc) 3303 [n(NH)] 2548 [n(SH)] and 1670 cm21 [n(C]] O)]. NMR (CDCl3) 1H d 7.15 (1 H br NH) 3.37–3.34 (1 H q J = 7.3 C3H) 3.13 (1 H br SH) 2.92–2.70 (6 H m C1,2,5H) 1.77–1.70 (1 H t J = 7 SH) 1.51–1.49 (3 H d J = 7 Hz C3AH) 1.38 (3 H s C6AH) and 1.37 (3 H s C6BH); 13C d 172.50 (C4) 52.28 (C5) 45.42 (C3) 44.54 (C6) 35.62 (C2) 30.15 (C1) 29.94 (C6A) 24.53 (C6B) and 18.79 (C3A).EI mass spectrum m/z = 132 [M 2 HSCH2- CH2SCHMe]1; and 254 M1. Proligand H3L8. The method used was similar to that for H3L1 but with compound 5 (1 g 4.78 mmol). The quantities of the other reagents were adjusted accordingly. An identical work-up procedure gave the required compound as a thick colourless oil. Yield 0.7 g (51%). IR (KBr disc) 3294 [n(NH)] 2554 [n(SH)] and 1650 cm21 [n(C]] O)]. NMR (CDCl3) 1H d 7.62–7.27 (5 H m Ph) 7.18 (1 H br s NH) 4.63 (1 H s C3H) 3.59–3.39 (2 H m C5H) 2.86–2.60 (6 H m C1,2,6H) 1.71–1.65 (1 H t J = 7.9 SH) and 1.49–1.25 (1 H t J = 8.5 Hz SH); 13C d 169.87 (C4) 136.59 (Ph) 128.95 (Ph) 128.89 (Ph) 128.52 (Ph) 128.01 (Ph) 127.74 (Ph) 54.49 (C5) 42.61 (C3) 36.31 (C2) 24.39 (C6) and 24.20 (C1).EI mass spectrum m/z = 209 [M 2 HSCH2CH2S]1; and 287 M1. Proligand H3L9. The method used was similar to that for H3L8 but with 1-amino-2-methylpropane-2-thiol hydrochloride (0.68 g 4.78 mmol) in place of 2-aminoethanethiol and a solvent mixture (70% CH2Cl2–30% thf ) in place of CH2Cl2. The quantities of the other reagents used were adjusted accordingly. An identical work-up procedure gave the required compound as a thick colourless oil. Yield 0.7 g (51%). IR (KBr disc) 3326 [n(NH)] 2556 [n(SH)] 1657 [n(C]] O)] and 729–698 cm21 (Ph). NMR (CDCl3) 1H d 7.8–7.46 (5 H m Ph) 7.03 (1 H br s NH) 4.65 (1 H s C3H) 3.35–3.33 (2 H d J = 6 C5H) 2.88– 2.68 (4 H m C1,2H) 1.71–1.65 (1 H t J = 8 Hz SH) 1.59 (1 H s SH) 1.32 (3 H s C6AH) and 1.28 (3 H s C6BH); 13C d 169.77 (C4) 136.65 (Ph) 129.00 (Ph) 128.90 (Ph) 128.34 (Ph) 128.01 (Ph) 54.81 (C5) 52.41 (C3) 45.49 (C6) 36.37 (C2) 30.03 (C6A) 29.86 (C6B) and 24.29 (C1).EI mass spectrum m/z = 224 [M 2 HSCH2CH2]1; 316 M1. Proligand H3L10. Compound H3L1 (2 g 9.47 mmol) was dissolved in dry degassed thf (50 cm3) and borane in thf (46 cm3 5 equivalents) was added. The mixture was heated under reflux overnight under a nitrogen atmosphere. Solvent was removed under vacuum distilled water (10 cm3) was added (to hydrolyse the borane complex) and H3L10 was extracted with CH2Cl2 (75 cm3) and washed with water (2 × 20 cm3). The organic layer was dried over MgSO4 and then filtered. Solvent was removed under reduced pressure and the residue dried under vacuum to give the required compound as a clear colourless oil.Yield 1.1 g (59%). IR (KBr disc) 3288 [n(NH)] and 2542 cm21 [n(SH)]. NMR [(CD3)2SO] 1H d 8.26 (1 H s NH) 2.93–2.53 (12 H m) 1.35 (1 H br SH) and 0.89–0.87 (1 H t SH J = 7 Hz); 13C d 51.58 (C5) 48.24 (C4) 35.13 (C3) 31.22 (C2) 24.32 (C1) and 24.15 (C6). EI mass spectrum m/z = 164 [M 2 SH]1; and 198 M1. Technetium-99 complexes. Ligand L1. The salt [NBu4]- [TcOCl4] (75 mg 0.15 mmol) was dissolved in dry methanol (3 cm3) under a nitrogen atmosphere. Proligand H3L1 (61 mg 0.28 mmol) was added as a solution in methanol (1 cm3) causing the immediate formation of a red-brown precipitate and the solution changed from green to orange. The mixture was heated at reflux for 1 h but no further changes were apparent. The solid was filtered off and analysis of the filtrate by TLC and HPLC showed that it contained a single clean technetium species.Solvent was removed under vacuum to give the pure product as an amber coloured oil. Yield 61 mg (131% if product is [TcOL1] 72% if [NBu4][TcOL1]). IR (thin film salt plate) 1634 [n(C]] O)] and 948 cm21 [n(Tc]] O)]. NMR (CDCl3) 1H d 3.39 (2 H br s) 1.71 (2 H br s) 1.49 (2 H two br s overlapping) and 1.04 (3 H t J = 7 Hz); 13C d 59.6 24.4 19.9 and 13.8. HPLC retention time 9 min. TLC Rf = 0.57 (silica 10% methanol in dichloromethane). Ligand L2. This complex was prepared in the same manner using [NBu4][TcOCl] (51 mg 0.101 mmol) and proligand H3L2 (42 mg 0.19 mmol) in place of H3L1. An identical work-up procedure was used but the golden oil isolated was purified by column chromatography (silica 10% methanol in dichloromethane) to give the product as a yellow solid.Although the crude product was isolated in good yield most was lost during chromatography. IR (thin film) 3309 [n(NH)] 2919 [n(CH)] 1651 [n(C]] O)] 1434 1350 and 1298 cm21. HPLC retention time 9 min. TLC Rf = 0.69 (silica 10% methanol in dichloromethane). Ligand L4. This complex was prepared in the same manner with [NBu4][TcOCl] (38 mg 0.076 mmol) and proligand H3L4 (34 mg 0.12 mmol) in place of H3L1. An identical work-up procedure was employed giving the product as an amber coloured oil. Yield 43 mg (143% if product [TcOL] 89% if [NBu4]- [TcOL]. IR (thin film salt plate) 3416 [n(NH)] 2960 [n(CH)] 2874 [n(CH)] 1738 [n(C]] O)] 1643 [n(C]] O)] 1468 954 [n(Tc]] O)] and 883w cm21.NMR (CDCl3) 1H d 3.36 (2 H br s) 1.70 (2 H br s) 1.49 and 1.47 (2 H br s overlapping) and 1.02 (3 H t J = 13 Hz); 13C d 65.52 (br) 26.84 21.32 and 14.57. HPLC retention time 8.5 min. TLC Rf = 0.56 (silica 10% methanol in dichloromethane). [ReO(L1)]. The complex [ReOCl3(PPh3)2] (0.78 g 0.947 mmol) was added as a solid to stirred solution of H3L1 (0.2 g 0.947 mmol) and 1 mol dm23 aqueous sodium acetate (20 cm3 20 mmol) in methanol (10 cm3). The mixture was heated under reflux for 2 h during which time it became deep red-purple. It was cooled to room temperature and a green solid filtered off. No attempts were made to analyse this solid. Solvent was removed from the filtrate under reduced pressure and the residue taken up in dichloromethane (50 cm3). The filtered solution was washed with water (2 × 50 cm3) and dried over MgSO4.(Improved yields were obtained when the water–dichloromethane phases were allowed fully to partition on standing overnight.) The drying agent was filtered off and the solution concentrated under vacuum to about 5 cm3. A red-orange precipitate was formed upon addition of hexane filtered off washed with diethyl ether and dried under vacuum to give the required compound. An identical product was obtained in similar yield using [ReO2(py)4]Cl in place of [ReOCl3(PPh3)2]. Yield 0.12 g (31%) (Found C 18.1; H 2.5; N 3.4. Calc. for C6H10NO2Re C 17.5; H 2.5; N 3.4%). IR (KBr disc) 1634 [n(C]] O)] and 964 cm21 [n(Re]] O)]. NMR [(CD3)2SO] 1H d 4.90–4.83 (1 H d J = 17 C3H) 4.47–4.38 (1 H m C5H) 4.10– 4.02 (1 H d J = 17 C3H) 4.00–3.96 (2 H m C1,6H) 3.80–3.75 (1 H d d J = 2.3 2.64 C2H) 3.30–3.25 (2 H m C1,5H) 2.88– 2.77 (1 H t d 3J = 3.74 2J = 13.77 C6H) 2.06–1.95 (1 H d d d 3J = 4.4 2J = 14.6 Hz C2H); 13C d 190.38 (C4) 61.74 (C5) 44.41 (C2) 42.41 (C1) 42.27 (C6) and 40.44 (C3).FAB mass spectrum m/z = 289 [M 2 SCH2CH2SCH2O]1; and 412 [M 1 1]1. HPLC retention time = 8.5 min single species. Crystals suitable for X-ray diffraction analysis were obtained from dichloromethane–isopropyl alcohol. J. Chem. Soc. Dalton Trans. 1997 Pages 1403–1410 1409 [ReO(L2)]. The method used was similar to that for [ReO(L1)] but with H3L2 (0.2 g 0.83 mmol) in place of H3L1. The quantities of the other reagents used were adjusted accordingly. An identical work-up procedure gave the required compound as a brown-red solid. Yield 0.12 g (34%) (Found C 19.9; H 2.8; N 3.3.Calc. for C7H12NO2ReS3 C 19.7; H 2.9; N 3.3%). IR (KBr disc) 1637 [n(C]] O)] and 959 cm21 [n(Re]] O)]. NMR [(CD3)2SO] 1H d 4.56 (1 H d J = 17 C4H) 4.53–4.38 (1 H m C6H) 4.20 (1 H d J = 17 Hz C4H) 4.13–3.99 (1 H m C6H) 3.96–3.79 (2 H m) 3.64–3.33 (2 H m) 3.26–3.11 (2 H m) 2.44–2.34 (1 H m) and 2.19–2.10 (1 H m); 13C d 190.15 (C5) 61.46 (C6) 43.49 (C3) 38.08 (C4) 35.92 (C1) 35.23 (C7) and 24.29 (C2). FAB mass spectrum m/z = 426 [M 1 1]1. HPLC retention time = 7.75 min single species. Crystals suitable for X-ray diffraction analysis were obtained from dichloromethane –isopropyl alcohol. [ReO(L4)]. The method used was similar to that for [ReO(L1)] but with H3L4 (0.2 g 0.7 mmol) in place of H3L1. The quantities of the other reagents used were adjusted accordingly.An identical work-up procedure gave the required compound as a purple solid which is a mixture of two distinct species probably syn and anti isomers. Yield 0.12 g (36%) (Found C 22.0; H 2.9; N 2.8. Calc. for C9H14NO2ReS3 C 22.3; H 2.9; N 2.9%). IR (KBr disc) 1731 [n(C]] O)] 1650 [n(C]] O)] and 9.71 cm21 [n(Re]] O)]. NMR (CDCl3) 1H d 5.54– 5.52 (1 H d J = 6) 4.80–4.73 (1 H d J = 17) 4.46–4.58 (1 H d J = 17) 4.59 (1 H m) 4.55–4.53 (1 H d J = 6) 4.26–4.01 (7 H m) 3.99–3.72 (4 H m) 3.65–3.50 (2 H m) 3.01–2.88 (2 H m) 1.85–1.74 (2 H m) 1.32–1.27 (3 H t 2J = 7 3J = 15 Me) 1.24– 1.19 (3 H t 2J = 7 3J = 15 Hz C9H); 13C d 190.17 (C4 isomer A) 188.58 (C4 isomer B) 172.01 (C7A) 170.17 (C7B) 73.61 (C5A) 73.1 (C5B) 61.56 (C8A) 61.42 (C8B) 47.58 (C2A) 46.34 (C2B) 45.94 (C3A,3B) 43.18 (C1A) 43.05 (C6A) 40.83 (C1B) 40.64 (C6B) 14.19 (C9A) and 14.16 (C9B).FAB mass spectrum m/z = 437 [M 2 SCH2]1; and 483 M1. HPLC retention time = 6.5 7.25 min; two species ratio 1 1. [ReO(L5)]. The method used was similar to that for [ReO(L1)] but with H3L5 (0.25 g 1 mmol) in place of H3L1. The quantities of the other reagents were adjusted accordingly. An identical work-up procedure gave the required compound as a red-orange solid. Yield 0.18 g (40%) (Found C 21.9; H 3.3; N 3.1. Calc. for C8H14NO2ReS3 C 21.8; H 3.2; N 3.2%). IR (KBr disc) 1633 [n(C]] O)] and 959 cm21 [n(Re]] O)]. NMR [(CD3)2SO] 1H d 4.82–4.75 (1 H d J = 17 C3H) 4.27–4.23 (1 H d J = 13 C5H) 4.03–3.95 (1 H d J = 17 C3H) 4.01–3.95 (1 H m C1H) 3.79–3.74 (1 H d d J = 2 C2H) 3.2–3.24 (1 H d J = 13 C5H) 2.88–2.76 (1 H t d 2J = 3.5 3J = 14 C1H) 2.02–1.93 (1 H d d d 2J = 4.5 3J = 10.5 Hz C2H) 1.77 (3 H s 6-MeA) and 1.50 (3 H s 6- MeB); 13C d 191.00 (C4) 72.99 (C5) 58.29 (C6) 44.28 (C2) 42.39 (C1) 39.28 (C3) 30.11 (MeA) and 28.17 (MeB).FAB mass spectrum m/z = 440 [M 1 1]1. HPLC retention time = 7.75 min single species. [ReO(L6)]. The method used was similar to that for complex [ReO(L1)] but with H3L6 (0.2 g 0.88 mmol) in place of H3L1. The quantities of the other reagents were adjusted accordingly. An identical work-up procedure gave the required complex as a red-orange solid. Yield 0.12 g (32%) (Found C 20.0; H 2.9; N 3.3. Calc. for C7H12NO2ReS3 C 19.8; H 2.8; N 3.3%). IR (KBr disc) 1632 [n(C]] O)] and 974 cm21 [n(Re]] O)]. NMR [(CD3)2SO] 1H d 4.44–4.38 (1 H q d C3H) 4.14–4.02 (2 H m C1,2H) 3.96–3.91 (d d J = 2.67 3.29 C5H) 3.89–3.84 (1 H t d 3J = 2.19 2J = 5.65 C6H) 3.65–3.28 (1 H m C5H) 3.32–3.21 (1 H m C6H) 2.87–2.75 (1 H m C1H) 2.13–2.0 (1 H d d d 3J = 4.5 2J = 10.26 C6H) and 1.77–1.80 (3 H d J = 7.4 Hz 3-Me); 13C d 190.97 (C3) 61.75 (C5) 50.99 (C3) 44.41 (C2) 42.25 (C1) 41.05 (C6) and 18.94 (3-Me).FAB mass spectrum m/z = 367 [M 2 CH2CH2S]1; and 426 M1. HPLC retention time = 7 min single species. [ReO(L7)]. The method used was as described for [ReO(L1)] but with H3L7 (0.2 g 0.79 mmol) in place of H3L1. The quantities of the other reagents were adjusted accordingly. An identical work-up procedure gave the required compound as a brown-orange solid. The 13C NMR spectrum indicated two isomers A and the predominant B in ca. 1 3 ratio. Yield 0.155 g (43%) (Found C 23.9; H 3.6; N 3.1. Calc.for C9H16NO2ReS3 C 23.8; H 3.5; N 3.1%). IR (KBr disc) 1644 [n(C]] O)] and 954 cm21 [n(Re]] O)]. 13C NMR [(CD3)2SO] isomer A d 191.87 (C4) 73.95 (C5) 57.36 (C6) 49.80 (C3) 44.34 (C2) 42.30 (C1) 29.99 (6-MeA) 27.84 (6-MeB) and 14.71 (3-Me); isomer B 191.41 (C4) 72.98 (C5) 57.03 (C6) 49.80 (C3) 44.34 (C2) 42.30 (C1) 30.09 (6-MeA) 28.25 (6-MeB) and 18.87 (3-Me). FAB mass spectrum m/z = 426 [M 2 CH2CH2]1; 454 M1. HPLC retention time = 4.5 5.5 min; two species ratio 1 3. [ReO(L8)]. The method used was as for [ReO(L1)] but with H3L8 (0.2 g 0.69 mmol) in place of H3L1. The quantities of the other reagents were adjusted accordingly and an identical work-up procedure gave the required compound as a purple solid. Yield 0.12 g (36%) (Found C 29.9; H 3.1; N 2.9. Calc. for C12H14NO2ReS3 C 29.6; H 2.9; N 2.9%).IR (KBr disc) 1643 [n(C]] O)] and 965 cm21 [n(Re]] O)]. NMR [(CD3)2SO] 1H d 8.02–7.32 (5 H m Ph) 4.50–4.48 (1 H m) 4.00–3.64 (3 H m) 3.40–3.36 (2 H m) 2.88–2.78 (2 H m) and 2.33–2.29 (1 H m); 13C d 189.52 (C4) 142.05 (Ph) 137.44 (Ph) 129.23 (Ph) 128.80 (Ph) 128.24 (Ph) 127.16 (Ph) 62.38 (C5) 57.86 (C3) 44.80 (C2) 41.94 (C1) and 41.72 (C6). FAB mass spectrum m/z = 488 [M 1 1]1. HPLC retention time = 5 min single species. [ReO(L9)]. The method used was as described for [ReO(L1)] but with H3L9(0.2 g 0.63 mmol) in place of H3L1. The quantities of the other reagents were adjusted accordingly and an identical work-up procedure gave the required compound as a purple solid. Yield 81 mg (25%) (Found C 33.3; H 3.8; N 2.6. Calc. for C14H18NO2ReS3 C 32.6; H 3.5; N 2.7%). IR (KBr disc) 1607 [n(C]] O)] and 961 cm21 [n(Re]] O)].13C NMR (CDCl3) isomer A d 190.55 (C4) 146.70 (Ph) 141.95 (Ph) 128.38 (Ph) 128.29 (Ph) 127.72 (Ph) 127.35 (Ph) 60.00 (C5) 57.89 (C3) 56.70 (C6) 41.94 (C2) 41.32 (C1) 30.13 (6-MeA) and 29.68 (6-MeB); isomer B 190.20 (C4) 142.79 (Ph) 142.45 (Ph) 128.98 (Ph) 127.97 (Ph) 127.24 (Ph) 127.22 (Ph) 58.85 (C5) 55.83 (C3) 51.04 (C6) 41.63 (C2) 41.02 (C1) 29.44 (6-MeA) and 28.21 (6-MeB). FAB mass spectrum m/z = 456 [M 2 SCH2- CH2]1; 489 [M 2 CH2CH2]1; and 516 [M 1 1]1. HPLC retention time = 3.75 4.5 min; two species ratio 1 3. Oxorhenium(V) oxo complexes from [ReO4]2 SnCl2 and citric acid. [ReO(L1)]. Tin(II) chloride (0.07 g 0.37 mmol) was dissolved in 0.5 mol dm23 citric acid (5 cm3) and a solution of NH4ReO4 (0.1 g 0.37 mmol) in methanol (5 cm3) was added.The compound H3L1 (0.078 g 0.37 mmol) was dissolved in NaO2CMe–MeOH (10 mmol 10 cm3) heated to boiling and the hot solution added to the rhenium citrate solution. The pH was adjusted to ca. 8 by adding NaO2CMe and the mixture was heated under reflux for 2 h then filtered when cool. The solvent was removed under reduced pressure and the complex extracted with CH2Cl2 (50 cm3) filtered and the solvent volume reduced to 3 cm3. Diethyl ether was added and the solvent volume again reduced to 3 cm3. Addition of water precipitated an orange-red solid which was washed with water acetone and Et2O. Yield 30 mg (20%). IR (KBr disc) 1633 [n(C]] O)] and 964 cm21 [n(Re]] O)]. FAB mass spectrum m/z = 411 M1. This had identical spectroscopic properties to the sample prepared above from [ReOCl3(PPh3)2].[ReO(L5)]. The method used was similar to that for [ReO(L1)] from [ReO4]2 but with H3L3 (0.09 g 0.37 mmol) in place of 1410 J. Chem. Soc. Dalton Trans. 1997 Pages 1403–1410 H3L1. The quantities of the other reagents were adjusted accordingly. An identical work-up procedure gave the required compound as a red-orange solid. Yield 36 mg (21%). IR (KBr disc) 1633 [n(C]] O)] and 959 cm21 [n(Re]] O)]. FAB mass spectrum m/z = 440 [M 1 1]1. Identical spectroscopic properties to those of the compound prepared above. [ReO(L6)]. The method used was similar to that for [ReO(L1)] from [ReO4]2 but with H3L6 (0.084 g 0.37 mmol) in place of H3L1. The quantities of the other reagents were adjusted accordingly. An identical work-up procedure gave the required compound as a deep red-orange solid.Yield 33 mg (21%) single species by HPLC. IR (KBr disc) 1633 [n(C]] O)] and 969 cm21 [n(Re]] O)]. FAB mass spectrum m/z = 426 [M 1 1]1. [ReO(L10)]. The method used was similar to that for [ReO(L1)] but with H3L10 (0.2 g 1.01 mmol) in place of H3L1. The quantities of the other reagents were adjusted accordingly. The mixture was heated under reflux for 2 h at which time it was brown-purple. An identical work-up procedure gave the required compound as a brown-orange solid. Yield 0.16 g (40%) (Found C 18.3; H 3.2; N 3.5. Calc. for C6H12NOReS3 C 18.1; H 3.1; N 3.5%). IR (KBr disc) 941 cm21 [n(Re]] O)]. NMR [(CD3)2SO] 1H d 4.28–4.13 (3 H m C4H2 C5H) 4.02– 3.96 (1 H d d J = 4.2 4.6 C6H) 3.92–3.87 (1 H d d J = 4.23 1.82 C1H) 3.75–3.69 (1 H d d J = 3.8 4 C2H) 3.53–3.47 (1 H d d J = 5.64 C2H) 3.39–3.28 (1 H m C5H) 2.98–2.86 (1 H d t J = 11.08 11.88 C6H) 2.73–2.61 (1 H t d 3J = 4.02 2J = 13.59 C3H) 2.50–2.37 (1 H t d 3J = 7.58 2J = 11.33 C3H) and 1.95–1.84 (1 H d d d 3J = 4.48 2J = 10.32 Hz C2H); 13C d 71.11 (C4) 70.81 (C5) 46.29 (C2) 45.43 (C3) 43.34 (C1) and 41.09 (C6).FAB mass spectrum m/z = 398 [M 1 1]1. HPLC retention time = 3 min single species. Crystals suitable for Xray diffraction analysis were obtained from dichloromethane– isopropyl alcohol. Crystallography Data collection. Intensity data were collected at 293(2) K on an Enraf-Nonius CAD 4 diffractometer {or in the case of [ReO(L2)] on a Delft instruments FAST area detector 10} with monochromated Mo-Ka radiation (l 0.710 73 Å). Cell constants were obtained from least-squares refinement of the setting angles of 25 centred reflections.The data were collected in the w–2q scan mode and three standard reflections were measured every 2 h of exposure. The losses of intensity reported in Table 1 were observed and linearly corrected during processing. Three standard reflections were measured every 200 to check the crystal orientation. The data were corrected for Lorentz– polarisation factors and an absorption correction was applied using y scans of nine reflections. Structure analysis and refinement. The structures were solved by direct methods (SHELXS 86) 11 and refined on Fo 2 by fullmatrix least squares (SHELXL 93) 12. In the cases of [ReO(L2)] and [ReO(L10)] the structure determinations were performed using the instructions TWIN BASF1 in the refinement procedure.All non-hydrogen atoms were refined with anisotropic thermal parameters. The hydrogen atoms were included in idealised positions with Uiso free to refine. The weighting schemes used gave satisfactory agreement analyses. The scattering factors were taken from the sources given in ref. 1. Atomic co-ordinates thermal parameters and bond lengths and angles have been deposited at the Cambridge Crystallographic Data Centre (CCDC). See Instructions for Authors J. Chem. Soc. Dalton Trans. 1997 Issue 1. Any request to the CCDC for this material should quote the full literature citation and the reference number 186/398. Acknowledgements We are indebted to Amersham International for financial support of the technetium work and for the award of a postdoctoral fellowship (to M. J. R.) and to the Government of Iraq for the award of a one year studentship (to M.J. Al-J.) We also gratefully acknowledge the generous gift of rhenium metal from Hermann Starck GmBH Berlin. We are also grateful to the EPSRC Crystallographic Service University of Wales Cardiff for the collection of the X-ray data set for the complex [ReO(L2)]. References 1 M. Nicolini G. Bandoli and U. Mazzi Technetium in Chemistry and Nuclear Medicine Cortina International Verona 1986; E. Deutsch K. Lisbon S. Jurisson and L. F. Lindoy Prog. Inorg. Chem. 1983 30 75; M. J. Clarke and L. Podbielski Coord. Chem. Rev. 1987 78 253. 2 A. Davison A. G. Jones and M. Sohn Inorg. Chem. 1981 20 1629; D. Brenner A. Davison J. Lister-James and A. G. Jones Inorg. Chem. 1984 23 3793; C. S. John L. C. Francesconi H. F. Kung S. Wehrli and G.Graczyk Polyhedron 1992 11 1145; W. A. Volkert Technetium and Rhenium in Chemistry and Nuclear Medicine eds. M. Nicolini G. Bandoli and U. Mazzi SGEDitoriali Padova 1995 vol. 4 p. 17 and refs. therein. 3 J. D. Kelly C. M. Archer E. A. Platts A. E. Storey L. R. Canning B. Edwards A. C. King J. F. Burke P. Duncanson D. V. Griffiths J. M. Hughes and M. A. Pitman Technetium and Rhenium in Chemistry and Nuclear Medicine eds. M. Nicolini G. Bandoli and U. Mazzi SGEDitoriali Padova 1995 vol. 4 p. 259. 4 T. N. Rao L. M. Gustavson and A. Srivasan Nucl. Med. Biol. 1992 19 889. 5 C.-S. Hilger L. Dinkel-Borg W. Kramp and H.-M. Schier Int. Pat. Appl. WO 94/22493 13th October 1994. 6 B. M. Trost K. Hiroi and L. N. Jungheim J. Org. Chem. 1980 45 1839. 7 C. K. Johnson ORTEP Report ORNL-5138 Oak Ridge National Laboratory Oak Ridge TN 1976.8 A. Davison C. Orvig H. S. Trop M. Sohn B. V. DePamphilis and A. G. Jones Inorg. Chem. 1980 19 1988. 9 J. Chatt and G. Rowe J. Chem. Soc. 1962 4019; M. S. Ram and J. T. Hupp Inorg. Chem. 1991 30 130. 10 J. Larsen and C. Lenoir Org. Synth. 1993 72 265. 11 G. M. Sheldrick Acta Crystallogr. Sect. A 1990 46 467. 12 G. M. Sheldrick SHELXL 93 Program for Crystal Structure Refinement University of Göttingen 1993. Received 5th September 1996; Paper 6/06112E
ISSN:1477-9226
DOI:10.1039/a606112e
出版商:RSC
年代:1997
数据来源: RSC
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