Indian Journal of Chemistry Vo1.38A , October 1999, pp: 985-990

Use of barbituric acid as a "padlock" to generate azamacrocyclic complexes of Ni(JI) containing fused aromatic rings

Nita A Lewis Department of Chemistry, University of Mi am i, Coral Gables, Flo rida 33 124, USA

and Goutam K Patra, Sanchita Hati & Dipankar Datta"

Department of Inorganic C hemi stry, Indian Association for the Cultivation of Science, Calcutta 700032, India Received 10 May 1999

1,5-Di(4,5-disubstituted-2-aminophenyl) penta- I ,5-diaza- 1 ,3-dienatonicke l(l l) chlorides are reacted w ith fo rmaldehyde and barbituric acid in the presence of catalytic amount o f perch loric ac id to synthesize two members of a new type of aza macrocyclic complex of Ni(ll) . The macrocyclic complexes, whi ch are diarnagnetic, have been characteri sed by conductiv ity, electronic spectra, thermal analysis and NMR (I H and 13C) spectroscopy . The structure of the cation in one of the macrocyclic complexes has been examined by using molecular mechanics.

Scheme I describes a ring c losing reaction for metal complexes having two free - NH2 groups on the same side where formaldehyde and a diprotic carbon acid AHz are used as ring closing reagents. in such a reaction, the formaldehyde first forms a sch iff base and the AH2 fragment then fitmly locks the ring .1 Accordingly, some authors have named AHz as a "padlock".1 So far, nitroethane,2-4 diethylmalonate) and barbituric acid6 have been employed as effective padlocks. Evidently, Scheme 1 can be used to generate azamacrocycl ic complexes. However, hithelio, such macrocyc1es have been synthesized from metal complexes of ethylenediamine and alkyl tetramines 1-3,6. There is no report of its application to complexes containing free aromatic - NI-I2 groups. it has been felt by several workers that macrocycles with fused aromatic rings have greater thermodynamic stab ility than their alkyl analogues7.8 . Recently, we have undertaken a proj ect to synthesize macrocycl ic complexes having four nitrogen donor centers and fused aromatic rings, wh ich are limited in number. 8

-11 Herein , we make the first report of our

efforts where barbituric acid is used as AH 2 in Scheme I and the two - NHz groups belong to 1,2-phenylenediamine fragments. The exact strategy is outlmed in Scheme 2.

Materials and Methods GR grade NiCh.6HzO, l,2-phenylenediam inc and

barbituric acid were procured from Loba-Chemie Indoaustranal Co. (India) , sodium chioride (GR) ,

formaldehyde solution (35%) and perchloric acid (70<%) from E. Merck (India) Ltd . and I , I ,3,3-tetramethoxypropane (99+%) and 4,5-d imethyl- I ,2 -phenylenediamine from Lancaster (UK) . Prior to use , l,2-phenylenediamine was recrystallised from 1:9 water-ethanol mixture . Deuterium oxide (99 .9 atom% D) was procured from Sigma and deuteriated dimethyl su lphoxide (99 .9 atom% D) from Aldrich . All other chemicals were of AR grade. Nickel was estimated gravimetricall y as the dimethylglyoximate . MicroanalYges were performed by a Perkin- Elmer 240011 elemental analy~er. Molar conductance (AM)

Scheme 1 - M : a metaJ ion

(I)

Scheme 2 - (i) H.CO, barbituric acid and C1IIaIytic amo\lllt ofperchloric acid

986 [NDIA J CHEM, SEC. A, OCTOBER 1999

was determined by a Systronics (India) di rect reading conductivity meter (Model 304) . IR spectra (KBr disc) were recorded on a Perkin-Elmer 783 spectrophotometer and UV N IS spectra on a Shimadzu UV -1 60A spectrophotometer. Magnetic susceptibility was measured by a PAR 155 Vibrating Sample Magnetometer fi tted with a Walker Scientific magnet; the magnetometer was calibrated with Hg[Co(SCN) 4]. Thermal analysis (TG-DT A) was performed by a Shimadzu DT-30 Thermal Analyzer in dynamic atmosphere o f dini trogen (flow rate: 30 cm3 min·l) wit}-1mert alumina as reference; the sample (particle size 'v ithin 150-200 mesh) was heated in a platinum crucible at a rate of lOoC min· I IH_ and I3C_ NMR were recorded by a Brucker DPX300 spectrometer in deuteriated dimethyl sulphoxide; DEPT (dynamic enhancement by polarisation transfer) spectra were recorded by using DEPT 90 and DEPT 135 programs to indentify methylene and quaternary carbons.

Syntheses (1 0) and (lb) CI-These were synthesized by

modifying a reported procedure l2 in the fo llowi ng manner. Recrystall i~ed l,2-pheny lenediamine (2.16g, 20 mmo]) NiCI2.6H20 (2.38g, 10 mmol) were taken in 100 cm3 of water. To the resulting greenish-brown solution, 1, 1,3 ,3-tetramethoxypropane ( 1.65 cm

3, 10

mmol) was a(!ded dropwise wi th stirring and the reaction mixture was boiled under re fl ux for 15 min [within ) min of refluxing, shining reddi sh-brown compound, (Ia) CI - the chloride salt of la started precipi aungJ. The reactiOl ' --rllxture was then left in the air for 3 h . Then (Ia) C i was fi ltered out , washcd with 25 em} of watvr and dried !II vacuo over fused CaCh; yield: 1.41 g (40%) . This compound was used for the isolation of 2a without further pUlification . /\ sim ilar procedure was fo llowed to synthesizc (1 b) CI usmg 4,5-dimethyl-I ,2-phenylenediamine; yiFld: 67%.

(2a) CI.6H20 and (2h) C1.3H20-O .35 g (l lllrnol j

of (Ia) CI was dissolved in 75 cmJ of methanol. A small amount of insoluble material was remowd by filtration. To the yellowish red filtrate, 0.22 ":',' (2 mmol) of formaldehyde and two drops of pc,·,:t1I onc acid were added. To the resulting solution, barnitllrtc acid (0.16 g, 1.25 mmol) dissolved in IOcr. I. : methanol-water mixture was added dropwls~ \)';cr a period of 30 min under retluxing condit ion. I he reaction mixture was then refluxed for anothcr 3 iJ, cooled to room temperature and then kept in the

re fr igerator for 3 h. The dark redd ish brown precip itate so obtained was fi ltered, wa hed With 5 em} of methanol and dried in air. (By foll owing a sim ilar procedure where the addition of formaldehyde is om itted, no compound could be isolated at this stage) . Next day, the whole amount of the precipi tate was di ssolved in 20 cm3 of dimethyl sulphoxide (DM SO) . To this clear dark red solution , sodium chloride (5 g) di ssolved in 80 cm3 of water was added dropwise with constant stirring. Towards the end of the addition of NaCI solution, a dark red compound started appearing. The mixture was kept in the refrigerator overnight. Then the compound was filtered out, washed thoroughly with 10 cm3 of water and dried by keeping in a vacuum desiccator containing fused CaC I2 for 24 h; yield: 0. 18 g (30%) . It analysed as the hexahydrate of the chloride salt of 2a - (2a) C1.6H20 [Found: C, 41.78; N, 13 .76; H ,

5.02 ; i, 9.76 . Calc . for C21 N6H310gCIN i : C, 41.62; N, 13 .87; H, 5.1 6; Ni, 9.69%]. A sim ilar procedure was followed for synthesising (2b) CI.3HP starting with a suspension of 0 .40 g (1 rnmol) of (1 b) CI in 75 cm3 of methanol ; yield: .41 g (67%) . Elemental analyses were consistent wi th the stoichiometry C25N6H330 6ClNi [Found : C, 49.35; N, 13.67; II , 5.45; Ni , 9. 72 . Calc. : C, 49.38; ,1 3.82; H, 5.47; i, 9 .66%]. IR data (cm· l

) for (2a) CI.6Hi O : 3400 (b) , 3200 (b) , 3040 (b) , 2830 (b) , 1700 (vs, b) , 1590 (s) .15 10 (v , splitted) , 1460 (s) , 1370 (m), 1325 () , 1280 (m), 1240 (w) , 11 90 (b), 1120 (m) , 1100 (w) , 1020 (s, b) , 955 (m) , 765 (s) , 630 (w, b) , 550 (m, splitted) , 510 (w) ,410 (s) . IR data (em·l) fo r (2b) CI.3 H20 : 3400 (b) , 3200 (b) , 3025 (w) , 1745 (w) , 1695 (s, b) , 1590 (b) , 1555 (w) , 1505 (rn) , 1460 (vs) , 1370 (s) , 1320 (vs) , 1200 (s) , 1120 (s) , 1085 (w) , lO GO ( \\1) , 10 15 (rn) , 995 (m) . 945 (\',1) . 9 10 (w) , 870 (m) , 83 5 (w, b) , 775 (w, b) , 730 (\ ) . 660 (w. b) , 630 (w) , 545 (m) , 5 10 (w) .

Molecular I1lecilan ics calculatiulls These were perfon-ned w ith the CAChe sui te of

programs available from Oxford Molecular Group Inc 1.1 This prOh'Tam starts \'itl II t: MM2 forc e i'ldd d .... \·~lollCd by f lIingcrl4 ;md Jl'I!m eUS .~ in three

vays: ( I ) l:xle ndin~ the force ficld 10 <.!udltlOlla l bond and ·' tom types by includ ing weak, Joordin<lte and iilH ' bond, and alums with hybl i,jlsations h. ·~l li.:r than

sp' , (2) I'ccogl,ising conj ugated and otllel aromat ic systems, and (3) systematically apply in.L; a s't of empiri cal ru les wh ich esti mate missmg force -field constants. The energy terms for bond strctch, bond

LEW IS el at.: AZAMACROCYCLIC CO MPLEXES OF Ni(ll) 987

Table I-Physical properties of(2a) C .6 H20 and (2b) CL3 H20

Measurement (2a) C I. 6H 2O (2b) CL3H 2O

I.So lut ion conductivity 62" 55" AM/mho cm2 mor l

2. Magnetic moment Diamagnetic Diamagnetic 3. vc<!cm- I 1700b 1695 b

4 . Water loss (%) 18.0 I c.d( 17.85e) 8.58 C(8 .89<) TG

5. Electronic spectra (a) in nujol: /Jnm 550sh, 485, 545sh,480,

3 15sh 3 10sh (b) in DMSO; /Jnm 476 (14 000) , 482 ( J 9 SOO) ,

450sh (J 3 UOO) , 46Ush (J 8 500) , (c/dm3 mol I cm-I) 320sh (6 600) , 325sh (7 :100) ,

263 (18900) :!68 ( 19 000)

' In DMSO. bIn KBr disc; center o f a very broad and strong band. cExperimental. dl n nvo steps. <Calcu lated.

angle, dihedral ang le, improper torsion, van der Waals, electrostatics and hydrogen bonding interactions are included in ea h ca1ct!lation. The covalent rad ius for i used in the CAChe augmented force fiel d is 1.150 A. Ni ckel is asslgneQ a hardness va lue of 0.185 and the vand er 7v'aals radius l5

employed for this meta l is 1.600 A. A block-diauona l Newton-Raphson technique was used for the optimisation process. Optimisation ,vas done un til the energy change is less than 0.00 i kcal mOrl. The cati on 2a was optimised to an energy minima twenty times, each attempt beginning from a different and often absurd geometry . n ly the reproducible optimisations obtained from several d ifferent attempts hJye aeen considered to represent the va lid global :'11..11na.

R .'1, ts and Discussion . 'l: cat ions 1a and I b h3 ve been iso la ted as the

('h',"ide salt - (Ia) CI and (tb) CI. r hese ca ll be de' .. bed as the NiCIn complexes of the half-cyc li sed

, 1 9·1 1 I' h ' ..., 2 d f' 3g,- s macrocyc e, w llC IS a _ + con ensate tl

':t:L '.lCetone and 1, 2-phenylenediamIne. The ',;'_ ··.' tion of the other half in l a and Ib ha s been

aL: '- ,'cd by reacting their chloridc salts WIth :~)l ::laldehycle and barbi turic aC id in 16: I mCllIan ol­\',,'Lllcr mixture (Scheme 2) . From th Is reaction , which is catalysed by an acid, the macrocyclic ca tioll 23 is Isolated as hexahydrate of Its c hloride salt - (2a) Cl.6H 20 and 2b as trihydrated chloride sa lt - (2b) C1.3H 20. The IR spectra is fLIIly consisten t w ith thei r

Table 2-NMR data ( 'fppm fro m TMS) for (2a ) Cl.6 H20 and (2b) CI.3H 20'

(2 a ) C I. 6H 2O

IH -NMR Meth yl protons Meth ylene protons 25 1 (s) C-CH-C proton 6.67(b) N H proto ns 6.30(sharp,s) H20 protons 1090-1 1.62d

Other protons 7.06-7.66<

IJC-NMR Methyl C Mcth ylene C 61 .63 Carbonyl ,'s 173.28 Alkyl qualt?lI1a~ C 104.1 9 Aryl quatcrnary C' s 134.44, 148.88

Ot her C's 114.47,124.60, \25 .75 , 127.96, f45.96, 149.74

aAbbreviations: s, sing let; b, broad. cCo uld not be di scerned properl y dThree broad signals <Ten in nu mber. fS ix in number. gBearing CH ~ group.

(2b) C1.3H 2O

2. J J (5) , 2.1 7('$) 244(5)

e

5 .97(sharp, s) J 1.53(sharp, 5)

6. 94-74i

20.92,2 J .66 63.38 J 75.09 105 .24

134.5 7~, 137.78, 14844, 15 142

g

J 16.64, 128.23, 133.53, 146. 79

formulati on. A very strong and broad band at 1700 cm-I

, which is absent 111 I a and 1 b, is due to the keto groups of the barbituric acid fragment in 2a and 2b . The presence of the watcr mol ecules in the two macrocyclic complexes have been confirmed from elemental and thermal analyses . In the case of (2b) C1.3H20 , TG-DT A shows that three molecules of wa ter are lost in one step over 50- JlO°C. In TG-DTA, (2a) Cl.6H20 also loses three molecules of water over

almost the same temperature range (50-130°C) : however, it loses tlu'ce more water molecules in 3

second step over 1 ~0 -250°C'. Both the macrocyclic compl exes (2a) C 1. 6H70 and (2b) C I.3H)O are found to be diamagnetic in the solid state suggesti ng a square planar arrangemen t for the Ni(II) center. Thi s means that none o f the water molecules as well as the chloride anion IS coordinated to the metal in the two macrocyciic com plexes . The non-coord inating nature of the chloride ion is supported by the I: 1 electrolytic behavIOur of (2a) Cl.6Il 20 and (2b) C1.3H,O in DMSO solution (Table I) . ThLI S it secms the water mo lecules whi ch are lost in the lower tcmperature r:.ll1ge are simple water of crysta llisation. Thc three water molecu les of (2a) CJ.()I-120 whi ch are lost over the higher tempera ture range are poss ib ly hydrogen

988 TNDlA ' J CHEM, SEC. A, OCTOBER 1999

f ig. 1- "8a ll and st ick" representations of the m inim um encrgy structurc o f the macrocyc li c cation 2a obtained by mo lccu lar mechan ics. (a) top vicw, (b) side on view . Atom identifi cation: N i, larger black ; N, smaller black; 0, black w ith a hole; C. blacki sh grey; H, white.

fig . 2_u C-NMR of (2h) CI.3H 20 in DMSO-d'r For the

possible assignment of the vario us resonances, sec Tabl" 2.

LEW IS (!( at.: AZAMACROCYCLlC COMPLEXES OF Ni(ll) 989

bonded to the carbonyl 0 atoms and/or the NH groups of the barbi turate fragment. This is in accord with Ih(; general behaviour of the barbiturates which usually crystallise with H-bonded water molecules. 6

The barb iturate group in (2a) CI.6Hl) and (2b) C1.3H20 greatly affects their solubility. While (la) CI and (lb) Cl are quite soluble in almost al l polar solvents, (2a) C1.6H20 and (2b) C1.3H20 are soluble in only DMSO and sparingly so in other polar so lvents like methanol , dimethylforn1amide, etc . However, our macrocyc lic complexes are moderately soluble in ac idul ated methanol. These dissolve in water under alkaline condition (pH= lO) . But, on

keeping, (2a) CI. 6H]O and (2b) C1.3H20 decompose in alka line aqueous solution, from which white crystals· of barbituric acid can be iso lated; this indicates that addition of base brings about the back reaction in Scheme 2. In contrast, the macrocyclic copper(IJ) complex synthesized by Lampeka el 01. 6

from the reaction of formaldehyd e and barbituric acid with I , II -diamino-4,8-diazanonane copper(lI) perchlorate, is quite stab le in al kaline aqueous medium.

The o lution electronic spectra (in DMSO) of the macrocycl ic complexes. (2a) Cl. 6H20 and (2b) C1.3H20, in the visib le rcgion arc basically composed of two in tcnse charge transfer bands around 480 and 265 nm (Table I) , the band around 480 nm being responsible for their wine red colour in solution . Their electronic spectra are almost sim ila r to those of ( Ia) Cl and (1 b) CI in DMSO. Thus the presence of the barbiturate fragment in' (2a) Cl.6H 20 and (2b) C1.3 H20 cannot be discerned fro m their electronic spectra.

Because of the solubil ity problem, we have not yet been abl e to grow single crystal s of (2a) Cl.6H20 or (2b) C1.3H20. Usua lly Jager 's macrocyc le leads to sJddle shaped molecules.9,lo In order to check what kmd o f geometry is spanned by the macrocycle in 2 around the Ni(II) center, we have performed molec ular mechanics (MM) calculation on the macrocycli c cation 2a . The minimum energy MM sti llcture of the ca tion is shov.1l in F ig. 1. It is \Jot saddl e shaped . Here both the H atoms on the two N atoms belonging to the I, 2-phenylened iamine fragment are on the same s ide of the plane passing through the NiN4 moiety and on the other side is located the barbiturate fragme]t which adopts a spiro conformation, as expected . Our MM ca lculations show that its isomer where the two hydrogen atoms in

question can be opposite to each other is higher in energy by 4.64 kcal mOrl .

Our MM structure (Fig. I) shows that the plane containing the barbiturate moiety divides the cation 2 into wo identical habes . This plane of symmetry IS

preserved in solution also as evidenced by its NMR spectra (Table 2 and Fig. 2) . The two methylene groups are found to be magnetica lly equivalent in the IH-NMR spectra as well as in the J3C-NMR spectra Cf able 2 and F ig. 2) . In the IH-NMR spectTa of (2a) C1.6H20, the C-CH-C proton appears as a somewhat broad signal at 6.67 ppm [this proton in (Ia) CI appears as a tri.plet l2 at 5.68 ppm in acetone-d6} but the same proton in (2 b) C1.3H10 could not be located

properly !ll its IH-NMR spectra though the corresponding C atom is very much present in the IJC_ NM R spectra (Fig. 2). Rather sharp signa ls are observed for the fo ur NH protons in both the macro~yclic complexes. Earlier, we have found from the TG-DT A analysis tha t there are at least two types of water molecules in (2a) C!.GH20. In the IH-NMR spectra while a single signhl is observed for the OH protons in (2b) C1.3H20 at 11.53 ppm, three broad signals are observed in the region 10.90-11.62 ppm for the OH protons in (2a) CI.6H20 . The NH and the various OH signals disappeared in the IH-NMR spectra with the addition of D 20. In the 13C_NMR spectra of the two macrocyc lic complexes (Table 2, Fig. 2), the keto C's appear in the expected region. 16

Concluding remarks Previously, the metal ion M employed in Scheme 1

has been mainly Cu(ll ); in only one repolt4

, Ni(lI)

has been used. Earlier, only Lampeka et i.J /6 have made use of barbi turic acid as AH2 in Scheme I to generate a macrocyc lic compound Crom the Cu(I l) complex of I , j l-diamino-4,8-diazanonane. Interestingly, the same reaction has reportedly failed for the corresponding Ni(JI) complex.6 This is possibly due to the fact that Ni(II) forms less stable complexes with tetramine schiff bases than CLI(l I)I. Here we have demonstrated the successful use of barbituric ac id as a padlock to generat a macrocyclic complex of Ni(IJ) containing fused aromati c ri ngs. It IS or interest to note that the coppel (II) analogue of I is not known.

Acknowledgement DD thanks the DST, lew Delhi. Govt. of Jnd ia fo r

fi nancia l assistance . Thanks are also due to Mr. J P askar for various types of help.

990 I DIA N J CHEM , SEC. A, OCTOBER 1999

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