Template Synthesis of Macrocyclic Complexes A Laboratory Project for Advanced Undergraduate Students James H. Cameron Heriot-Watt University, Riccarton, Edinburgh, UK EH14 4AS The rich chemistry of the complexes of macrocyclic ligands continues to he a subject of growing importance, as reflected by a number of recent reviews and books ( 1 ) . Much of this work has been stimulated by the recognition of the high kinetic and thermodynamic stahility of the complexes formed by macrocyclic ligands, the so-called "macrocyclic effect" (2), and also by the realization of the key importance of cyclic ligand systems in biology, for example, the protoporphyrin IX ligand of heme, or the corrin system found in the Vitamin B12 coenzyme (3).Because of this work, macrocyclic ligands are discussed routinely a s an integral part of any course on transition metal coordination chemistry. However, comparatively few undergraduate experiments are available to illustrate the practical side of macrocyclic synthesis, although one example, of the synthesis of a binuclear macrocycle, was reported fairly recently (4). Many of the synthetic routes to macrocyclic ligands involve the use of a metal ion template to orient the reacting groups of the ligand in the desired conformation for optimum ring closure. The favorable enthalpy for the formation of the metal-ligand bonds overcomes the unfavorable entropy from the ordering of the multidentate ligand around the metal ion and thereby promotes the cyclization reaction. This phenomenon has been described as the "coordination temolate effect" (5).Here. we wish to describe a slmplc., yet elrertwe. Idborntory project lor advanced undercraduares whtch dcnionstrares the appl~c;~tmn of this ternplating effect. As well as giving usefur practical experience in the preparation of cyclic ligands, this project also develops a number of skills in the students, in terms of both organic and inorganic synthesis, spectroscopic analysis, and team work, in the discussion and comparison of results. The full project is designed to be carried out conveniently in three laboratory sessions of three hours each; however, instructors may wish to tailor the project to their needs by focussing only on selected areas, such a s the ring closure step of the process, and the spectroscopy of the resulting macrocycles. This can be done readily by providing the acyclic intermediates as starting materials.
j, RsR'=oCsH,: k, R = c-CsH4 ; R' = (CHJ* I, R r 0-CsH, ; R' = (CW, rn, R = o.C& ;R' =CHzCH(CHJ
Preparation and Characterization of the Macrocyclic Complexes
Figure 1. The reactlon scheme used in this experiment.
The project is based upon the work of Jager (61, involving the synthesis of a family of tetraaza macrocyclic complexes of variable ring size, following the synthetic procedure outlined in the reaction scheme (Fig. 1). Complexes of this g ( w m l type recently h a w hvcornc vely important because Buwh and h ~ co-worker.; s hn\re used some euarnpl(ssad the bases for their eleeant work on the ~renarationof the bicv" clic and indeed tricyclic complexes that contain molecular voids a s an inteeral Dart of their molecular architecturethe "lacunar eycKdenknligands (7). Afeature that makes Jager complexes suitable for study in a l a h o r a t o ~project of this type is the wide range of products that can be produced by minor modification to the general synthetic procedure. For example, by changing the
diamine used in step one of the reaction, a variety of intermediates can be formed, limited only by the availability of diamino comoounds. For convenience, it is found that a group size of ahout four or five studentsis optimum, as this allows for efficient information transfer within the m o u ~ . without having too many compounds to he discussed. The starting material for macrocyclic synthesis is 3ethoxyvinylidene-2,4-pentanedione,1.This is prepared in reasonable yield from 2,4-pentanedione and triethylorthoformate, in the presence of acetic anhydride (8). Although this reaction could he carried out by the students, it is far more convenient to provide 1 as a starting material. The literature procedure suggests that 1should he used imme-
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Volume 72 Number 11 November 1995
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Table 1. 'H NMR Dataa --
compound
1
-
2-10 (s,3H)
1
2 2.15 (s,3H)
11.1 (brs,2H) 11.1 (brs. 2H) 12.98 (br s, 2H)
7.30 (s.2H)
3.20 (t,4H) J=6Hz
1.84 (q, 2H) J=6Hz
3.30 (s,4H) 3.63 (t,4H) J =6.5Hz 2.82 (br s$H)
7.63 (s,2H) 8.05 (s,2H) 8.05 (s,2H)
1.80 (qn,2H) J =6.5Hz
3.0-3.7 (m,3H) 1.40 (m, 3H) 6.7-7.6 (m,4H) 6.73-7.5 h4H)
'Spectra recorded at 60 MHz in CDCb solution.
diately after it has been prepared, but we have stored it in a refri erator for several weeks with no perceptible ill effeets. The H NMR spectroscopic data of 1 are given in Table 1. The first variable is introduced i n the next stage of the synthesis, with the students being assigned a particular diamino reagent. For convenience, we have restricted our studies to l,2-diaminoethane, 1,3-diaminopropane, 1 2 diaminopropane, and 1,2-diaminobenzene, although i n principle any diamine could be used. The selected diamines offer the opportunity of interesting comparisons of the effect of minor variations i n the liaand structure uDon the physicocl~cnlicalproperties of'the resulting species. 'The three a l i ~ h o t l cdiamines r e x t with 1 lo vroduce, in good yield, the'acyclic species 2a-c a s white, or off-white solids, while 1,2-diaminobenzene produces pale yellow 2d. The IH NMR and IR spectroscopic data are given in Tables 1and 2. The observation of coupling between the N-H and both the alkene C-H and the N-CHz group, (in species derived from aliphatic diamines), suggests that the products adopt the secondary amine structure shown i n the reaction, rather than a n alternative form containing two imine and two hydroxyl groups. In the next stage, the tetradentate ligands are coordinated to nickel (11) ion. This ion is preferred as i t produces the air stable, square planar, diamagnetic complexes (3a-dl; the spectroscopic data are given in Tables 1and 2. The complexes can exist in a number of possible resonance forms, some of which are illustrated in Figure 2. Overall they are best described as containing a delo&ized n-network. Some interesting observations can be - .~hvsicochemical " made concerning the various complexes, and the students should be encouraged to discuss their findings within the group. For example, the structurally similar orangelred
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Journal of Chemical Education
Table 2. Infrared and Electronic Spectroscopic Data and Yield of Products -
vN-"
-
(cm-')
3218 3178 3217 3400
vc.0,
C=N
(cm1)
1640,1614,1580 7652,1614,1578 1630,1618,1580 1668,1627 1650,1592 1651,1574 1652,1584 1654.1600,1574 1628,1575 1622,1542 1614,1580 1623.1575 1634,1580 1650,1617,1593,1571 1640,1580
hmax (nm)
%Yield
530sh 475,540sh 520sh 544 507 503 481 516 520sh 530sh 510sh
85 85 95 77 97 80 50 75 60 76 40 50 45 97 66
species, 3a and 3c, have markedly different solubilites in various solvents, notably chloroform. This can be explained i n terms of the efficient packing of the planar 3a in the solid state (9). (Indeed, all of the planar species prepared in this work tend to be of low solubility). In 3c, packing is disrupted by the extra methyl group, presumably
&-
leading to a lower lattice energy and hence a higher solubility. Interestingly, the complex 3c is markedly solvatochromic, and the students should be encouraged to investigate this phenomenon by measuring its electronic spectrum in a range of solR vents of different polarity The final preparative step, that of template-controlled ring closure to form the macrocycles, allows introduction of the second variable, with the student being assigned a second diamine. Any of the same four diamines may be selected, although in Figure 2. Some of the resonance forms of the acyclic complexes.
-
&
TN\,/O rN\NI/O
LN/
kO +when
practice 1,2-diaminobenzene, a solid, was used only for the ring closure of 3d, producing the macrocycle 4j. For the liauid diamines. it is i m ~ o r t a n t to ensire that the reaction mixture is well stirred and that all of the mecursor complex i s solvated by-the diamine before the reaction mixture is heated strongly, otherwise decomposition of the complex may occur. There is the potential for formation of 1 3 different macrocycles, 4a-m; however, in our experience not all of these species are accessible via the standard route. This results from the well-known marked preference for formation of five-membered metallo- Figure 3. Some of the resonance forms of the macrocyclic complexes. chelate rings relative to the six-membered analogues. The practical result SpectroscopicAnalysis is that "transamination" reactions can occur, concurrent All of the products are readily amenable to analysis by with cyclization, probably via aminal intermediates. For 'H N M R spectroscopy, and the relevant data with assignexample, 1,3-diaminopropane is displaced by 1,2-diamiments are listed in Table 1.The integral of signal intensity noethane in the attempted ring closure of 3b to form 4d. is of key importance to spectroscopic interpretation. In Even with an acyclic complex with a five-membered ring, general students are able to interpret the data without for example 3a, use of a 12-diamine may result in tranproblems. Unusual features of the spectra are: ligands 2a, samination under the forcing conditions of the ring closure b, c show a doublet for proton 3 arising from coupling with reaction; for example, attempted formation of 4c from 3a the amino proton, and the signals of the R group also are and l,&diaminopropane actually produces macrocycle 4i. split by coupling with the N-H group. With 2b, the cou(Macrocycle 4g has been prepared using a milder procepling constants of the N-CHz protons with the amino produre, (10) and it is likely that conditions can be found for ton and the adjacent CH2 are;by chance, identical, causing the preparation of the other macrocycles, if required). this signal to appear a s a 1:3:3:1 quartet; both types of Thus, seven macrocycles are formed cleanly and in good methyl group in macrocycle 4e are isochronous (i.e., have yield (4a, b, e, h-j and 1)by the route herein described and identical chemical shifts). the spectroscopic data are given in Tables 1and 2. AnnmThe IR spectra are useful in fingerprinting the various ber of resonance forms are possible for these species (for species. The most important bands are those associated example, see Fig. 3) and, as with the acyclic precursors, the with the N-H and carbonyl groups and the relevant data best description is where the unsaturated parts of the are listed in Table 2. There is some ambiguity in the asmolecule contain a delocalized x-network. This is borne out signment of C=O or C=N stretches, but it is clear that coby X-ray structural data for some of the complexes that ordination of the ligands to Ni(I1) causes one of the carshow that both C-N bonds of each unsaturated group are bony1 b a n d s to drop by -20-30 cm-'. Subsequent of equal length and lie in the region of 130 pm, indicating formation of the macrocycle causes the second carbonyl the existence of substantial double bond character (9). band to shift down hy -20 cm-'. I t 1s mstrurtive to allow the students toattempt the synTho elwtronic spcctra ol the majority of the nlckel 111 t h ~ & of on(, ~ , more r of the "disfd\~t?dl( mucrocscIe~14 C, complexes reflect their rediorange coloration, displaying a d, f, g, k and m). Macrocycles are prodnced;ia these single Lax a t -500-550 nm. This is typical of square plaroutes, but not those which are expected. Careful analysis nar complexes of Ni(I1) with tetraaza macrocyclic ligands of the spectra of the products, in particular the integral of (11). The three predicted transitions for square planar the 'H NMR spectra, allows identification of the genuine Ni(I1) generally lie close together in energy and are not renature of each of the products. By allowing the students to solved, appearing rather as a single broad peak, a s found decide what macrocycles will, or will not, form, it is possiin this work. Complex 3b is an exception in that it is very ble to emphasize the stability of five-membered rings in dark red in color and has h,, a t 475 nm with a shoulder the metallochelate species. This exercise gives the student a t -540 run. The appearance of the major band a t hmax good experience in spectroscopic analysis and is instruc480 nm appears to be typical of complexes containing a sixtive in highlighting that chemical reactions do not always membered metallochelate ring (3b, 4e). Given the thergo as planned.
yo
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Volume 72 Number 11 November 1995
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modynamic prefrrmce for formation of five-memherrd m(~tallochelatcnnas, the hlaher enerm of the bands in 3b and 4e is a t first sight anomalous. I t can be rationalized by recognizing that the longer the metal-ligand bond length, then the less will be the repulsion between ligand and metal electrons, in effect lowering the energy of the filled d-orbitals. This will increase the size of the HOMOLUMO gap leading to a higher energy transition for (d, + d?,2j, species with the six-membered metallochelate rings. This proposal is lent some support by bond length data which show Ni-N bond lengths of -188 pm in species with sixmembered rings but only -184 pm in corresponding species which have five-membered rings (9). Project Report Individual students are required to submit a detailed written report on their own preparative work, while placing it in the context of the whole work of the group. This keeps the length of the student's report down to a manageable level. During the experimental work, the students are encouraged to discuss their results with their peers and on the final day of the project, all members of the group are brought together for oral nresentation of their results. ~ith~som preliminary e g i d a n c e from the instructor, each member of the group gives a five- tol0-min presentation on their synthetic and spectroscopic results. Thus, the group as a whole sees how individual member's complexes relate to all of the others. While student reaction to this opportnnitv to give oral presentation of results usually is positive, and m&t sce it 3s a valuable opportunity to sharpm their spoken commun~carionskills, clearly i t will not hc feasible for large classes and instructors will wish to modify the method of reporting results to suit their individual needs. Experimental Details All the synthetic procedures are adapted from the literature (12).
To a l-L flask is added 2,4-pentanedione (100 mL, 0.97 mol), triethylorthoformate (164 mL, 0.97 moll and acetic anhydride (182 mL, 1.93 moll, and, with rapid stirring, this is brought to reflux. After 30 min, the reaction mixture is dark red in color. At this point the ethyl acetate and acetic acid by-products are distilled off rapidly, under reduced nressure. Finallv. ".the nroduct is distilled under vacuum. to produce a pale yellow oil (yield: 97 g, 64%). The dark red residue of distillation is renortedlv.." nvronhoric in air a t ele. vated temperature, so the vacuum is released to nitrogen
a t the conclusion of the distillation. This reaction can be scaled to a much larger size, if required. Acylic Ligands, (2a-d) 'Ib a solution of 1 (15 g; 0.096 moll in EtOH (-50 an3)cooled in an ice bath was added a solution of the assigned diarnine (0.048 moll in EtOH (-25 em3). (It is necessary to warm the solution to dissolve 1.2-diaminobenzene).After addition was complete, the mixtuk was stirred for afurther 10 min and the product was collected by filtration and dried.
Acyclic Complexes of Ni(ll), (3a-d) The acvclic linand (2) was slurried in MeOH (-50 cm3) and the mixture was warmed to -50 "C whereupon one eauivalent of Ni(OAcb4H70 . . slurried i n MeOH. was added. For lizand2b. two equivalents of solid N ~ O H were added to dep>otonate the ligand. The mixture was stirred a t -50 "C for 20 min, cooled, and the products collected by filtration and dried. Macrocyclic Complexes (4a, b, e, h-j, 1) To t h e acyclic complex 3 was added t h e assigned diamine, -25 cm3 (or in the case of 12-diaminobenzene, a 10-fold excess) and the mixture heated rapidly to reflux, with constant stirring. After -20 min a t reflux the mixture was cooled and ice water added to nrecinitate the nroduct. This was collected by fi1tration;was'hed with 'copious amounts of water, and dried. Acknowledgment I thank the referee for a number of valuable comments and suggestions. Literature Cited 1. Melson,G.A.,Ed.CoodimtionChemialqofMocmeyclieCompounds:Plenum:New York, 1979 ; Cooper S. R.. Ed. Cmmn Compounds-lburord Fuiurp Applications; VCH: New York. 1992. 2. Cahbiness. 0. K;Margemm, D. W J A m Chem Soc. 1969,91,65404541. 3. Ochisi, E.I.G w m l PrineiplesofBiodamidq ofthe Elmm&is:Plenum:New York, 1987. 4. Hunfer, J.: Murphy, B.;Nelson. J . J. Chem Edue 1991.68, 59-63. 5. Thompaon, M. C.;Busch. D. H. J A m Chem. Soc ISM. 86, 36513656. 6. Jdger, E. 0.2.Chem. 1968.8.392393. 7. Alcock. N. W. : Padolik, P. A ; Pike, G. A : Kqlima, M.; Cairns. C. J.; Busch, D. H. Inorg Chsm 1980,29,2599-2607, and references therein. 6. de Wolfe. R. H. Corboxylic Ortho AcidDwiuafiues: Academic Press:New York, 1970;
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Journal of Chemical Education
. P lnor@znic Electronic ~ p e ~ i ~ r n r n2nd & ed.: Elseeer: Amsterdam, 11. L e u e r , ~ B. 1984. 12. Riley, D. P.;Buach, D. H. Inorg SynCh. 1978,18,3M4.
