Protonation equilibria and complex formation ability of 2-amino-3-aminomethyl-4,6-disubstituted pyridines

Polyhedron Vol. 4. No. 2, pp. 259-268, Printed in Great Britain.

1985

0277-5381/85 $3.00 + .OO 0 1985 Pergamon Press Ltd.

PRCYI’ONATIONEQUILIBRIA AND COMPLEX FORMATION ABILITY OF 2-AMINO-3-AMINOMETHYL4,6_DISUBSTITUTED PYRIDINES z. cmfmtm

padz. S~FANAC*

Laboratory of Analytical Chemistry, Faculty of Science, University of Zagreb, Strossmayerov trg 14,4 1000 Zagreb, Yugoslavia (Received 18 January 1984; accepted 16 April 1984) Abstract--The protonation equilibria of 2-amino-3-aminomethyl-4,6disubstituted pyridines were studied by potentiometric titrations and by W and “C NMR spectrometry. determined for Protonation constants log K, and log K, potcntiometrically 4-methoxymethyl-6-methyl (8.959 and 5.778), 6-methoxymethyl4methyl (8.964 and 5.407), and 4,6-dimethyl derivative (9.141 and 6.604), were compared with the values obtained by the spectrometric methods. Complex formation of these compounds with Cu(II), Ni(II), Zn(I1) and Co(I1) was investigated in solution whereby the outstanding effect of the pH value was established and the presence of the species with 1 : 1 and 2 : 1 ligand to metal ratios confirmed. Stability constants obtained by potentiometric titrations show a decrease of the complex stability in the order Cu > Ni > Zn with respective log fi, values of 5.85, 3.56 and 2.93. Series of complexes isolated in the crude state were characterized by elemental analyses and spectrometric data, the latter serving also as the basis for making an attempt at the discernment of the coordination mode and sites.

Manifold approaches pursued in the studies of aminopyridines comprise also the correlations of structure and ionization.’ The complex formation ability of a number of these heteroaromatic ligands presents another interesting topic.2-7 In both cases additional substituents have been shown to play a decisive role depending on the species and position of substituents. Therefore with available newly synthesised 2-amino-3-aminomethylpyridines bearing two more substituents we performed concurrently the determination of protonation constants and the investigation of complexation ability. The series comprised 4-methoxymethyl-6-methyl (ligand I), 6-methoxymethyl4methyl (ligand II) and 4,6-dimethyl (ligand III) derivative. The behaviour of the complexes formed with transition metals in solution and the characteristics of isolated crude species are discussed. EXPERIMENTAL Apparatus The IR spectra were recorded in KBr or CsBr pellets with Perkin-Elmer spectrophotometers Models 457 and 580B. The mass spectra were taken on a Varian MAT CH7 or a CEC 21- 11OC *Author to whom correspondence should be addressed.

instrument. Electronic absorption spectra were obtained using a Perkin-Elmer spectrophotometer Model 200. 13CNMR spectra were recorded on a Jeol JNM-FX-lOOFT spectrometer in 40 with tetramethylammonium chloride as internal standard at room temperature. The pH was measured at (25.0 -I-0.2)OC with a Radiometer PHM-64 pH/mV meter providing a reading accuracy to within * 0.002 pH units. Radiometer glass electrode G202 B and saturated calomel electrode K-401 were used. Before each measurement the assembly was standardized with two buffer solutions: 0.05 mol drnA3 potassium hydrogenphthalate (pH25T - 4.008) and 0.01 mol dm-’ sodium tetraborate (pH25q = 9.180).

Materials Dcuterium oxide, 99.5 atom. % D and dideutero-sulphuric acid, 99.5 atom. % D, 9698% in D20 were purchased from E. Merck, Darmstadt. Sodium deuteroxide was prepared by dissolving sodium in D20. Tetramethylammonium chloride, for synthesis, E. Merck, Darmstadt was recrystallized from the ethanol/petroleum ether system. All other chemicals and solvents were of analytical purity grade, Kemika, Zagreb. The quartz doubly distilled water was used throughout.

260

z.

CIMERMAN and z. STEPANAC

Procedures

Preparation of ligands. 2-amino-3-aminomethyl4-methoxymethyl-6-methylpyridine (ligand I), 2amino-3-aminomethyl-6-methoxymethyl-4-methy lpyridine (ligand II) and 2-amino-3-aminomethyl-4,6-dimethylpyridine (ligand III) were obtained as dihydrochlorides by courtesy of Dr. D. Koruncev, Pliva, Pharmaceutical and Chemical Works, Zagreb. Free amines were prepared and purified to analytical grade according to the procedure described in Ref. 8. The pure products were checked by elemental analyses, IR and ‘H NMR spectrometric data. Preparation of metal complexes. For all complexes 0.1 mol dme3 solutions of ligands and metal salts were used. The complexes Cu(ligand I)z SO, - 2H,O and Cu(ligand 111)$04 - 2HrO crystallized after mixing a methanolic solution of the corresponding ligand with an aqueous solution of cupric sulphate in the 3:l molar proportion. Zn(ligand 1)$04 precipitated readily from a methanolic solution containing zinc sulphate and a threefold excess of ligand I. Cu(ligand I)SO, * 3H,O was prepared by mixing equimolar amounts of ligand I and cupric sulphate dissolved in minimum quantities of methanol and water, respectively. The complex crystallized from this solution after it had been evaporated to half of the volume and kept at 0°C for several days. Cu(ligand I)z(CIO,k crystallized by the addition of a saturated aqueous solution of sodium perchlorate to the aqueous solution containing ligand I and cupric sulphate in the 3 : 1 molar proportion. Zn(ligand I) [B(C6HS),], and Ni(ligand I), [B(C,H,),], precipitated from an aqueous solution containing equimolar amounts of metal(I1) salt and ligand I in the presence of sodium tetraphenylborate. Characterization

of isolated complexes

Cu(ligand &SO, - 2Hz0, C,,H,N,OsSCu, violet crystals, m.p. 197°C (decomp.). Found (talc.): C 39.58 (38.74); H 6.46 (6.14); N 15.07 (15.06); S 5.37 (5.74); Cu 11.16 (11.38)“/,. IR spectrum, v”cm-’ rel. intensity: 3420 b, 3250 b, 3 120 b, 2930 m, 1640 sh, 1620 s, 1592 m, 1 70sh, 1470m, 1450m, 1395m, 1325w, 119Om, P 1170-1070 vs, vb, 975 m, 865 VW,800 w, 690 w, 613 s, 550 w, 420 vw. Cu(ligand II&SO4 *2Hz0, C,,H,N,O$Cu, violet crystals, m.p. 215°C (decomp.). Found (calcr): C 38.87 (38.58); H 6.02 (6.07); N 17.01 (16.87); Cu 12.76 (12.26)%. IR spectrum, D cm-’ intensity: 3420 b, 3260 b, 3140 b, 296Ow, 2920 w, 164Os, 162Os,

1595 s, 1570 sh, 1505 m, 1475 m, 1450 m, 1390 m, 1330 w, 1215 w, 1010-l 170 vs,vb, 975 m, 855 VW, 800 m, 700 vw, 612 s, 550 vw, 535 w, 410 w. Zn(ligand I)rSO,, C,,Hr,,N,O,SZn, white powder, m.p. 257 OC (decomp.). Found (talc.): C 41.09 (41.27); H 5.96 (5.77); N 16.28 (16.04)s. IR spectrum, v”cm-’ rel. intensity: 3420 b, 332Os, 324Osh, 319Os, 2930m, 165Os, 16OOs, 1595 sh, 1575 s, 1470 m, 1450 s, 1420 m, 1400 m, 133Ow, 12OOs, 1165sh, 1145sh, lllovs, 107Os, 1055s, 975s, 825m, 810m, 675m, 65Os, 613s, 590 m, 550 VW,490 VW,290 VW. Cu(ligand I)SO., - 3Hz0, CgHz,N30BSCu, green crystals. Found (talc.): C 27.43 (27.37); H 5.91 (5.36); Cu 16.28 (16.09)%. IR spectrum, v”cm-’ rel. intensity: 3380 sh, 326Ob, 3100sh, 164Os, 1620sh, 159Osh, 155Ow, 1480m, 139Ow, 131Ow, lllovs, 104Ovs, 96Os, 790 m, 630 m, 604 s. Cu(ligand Ih(ClO&, C,8H~N6010C12C~, brown needles, m.p. 185°C (decomp.). Found (talc.): C 34.86 (34.60); H 4.91 (4.84); N 13.57 (13.45)%. IR spectrum, v”cm-’ rel. intensity: 3470m, 341Om, 33OOm, 32OOm, 2930 w, 162Os, 16OOsh, 1560 w, 1540 w, 1470 m, 1435 w, 1390 w, 1145 vs, 1115 vs, 1090 vs, 960 w, 870 w, 830 w, 795 w, 690 w, 628 s. Zn(ligand I)[R(C,H,),],, C5,H,,N30B2Zn, white powder, m.p. 82 OC (decomp.). Found (AC.): C 77.21 (77.35); H 6.50 (6.26); N 4.85 (4.74)%. IR spectrum, v”cm-’ rel. intensity: 3420m, 3350m, 3210m, 3180sh, 306Os, 3OOOm, 1960 w, 189Ow, 1825 w, 164Os, 1625 sh, 1605m, 1575m, 148Os, 1425 s, 141Ow, 1395 sh, 1335 w, 1265m, 118Ow, 115Ow, 112Ow, 109Ow, 107Ow, 103Ow, 850,m, 735 vs, 710 vs, 625 w, 615 m, 605 m, 585 VW, 465 vw. Ni(ligand I),[B(C,H,)&, C,H,J%O,B,Ni, pink powder, m.p. 112 OC (decomp.). Found (talc.): C 74.50 (74.81); H 6.49 (6.66); N 7.88 (7.93); Ni 5.21 (5.54)%. IR spectrum, v”cm-’ rel. intensity: 3400 sh, 3300m, 3210m,, 306Os, 3005m, 2930 w, 195Ow, 1830 w, 1640 m, 1610 s, 1580 m, 1480 s, 1428 m, 14OOw, 13OOvw, 1265w, 1180m, 1150m, lllOm, 1030 w, 850 m, 736 vs, 710 vs, 625 w, 615 m, 605 m, 482 VW,462 vw, 420 vw. IR spectra of ligands for comparison, v”cm-’ rel. intensity: (ligand I) 3345 s, 3300 sh, 3180 s, 3005 w, 2925m, 2885m, 166Os, 1592s, 157Os, 146Os, 143Os, 1398s, 1325m, 1280m, 1190m, 1150m, 1090 s, 1080 sh, 980 m, 955 s, 940 s, 865 m, 815 s, 806m, 695w, 65Ow, 610m, 580m, 55Ow, 52Ow, 420 w, 355m; (ligand III) 3360 s, 33OOs, 318Os, 301Ow, 2975m, 2910m, 1665s, 1655 sh, 1592s, 1570 sh, 148Os, 1455 s, 1415 m, 1325m, 1272m,

Protonation equilibria andcomplex formation ability of2-amino-3-aminomethyl-4,6-disubstituted pyridines 261 1210 s, 1190 w, 1140 w, 975 w, 955 m, 920 s, 860 m, 815s, 79Os, 690m, 64Om, 610m, 55Ow, 54Ow,

505 w, 410 w, 362 w. Determination of the protonation constants of ligand I by i3C nuclear magnetic resonance. Samples were obtained in the following way: a 0.447 mol dmm3 solution of ligand I was prepared by dissolving a weighed amount of compound in 40 and dividing it into a series of aliquots. The pD of each aliquot was adjusted with a concentrated solution of NaOD or D$O, in 40, and the ionic strength of 2.0 (NaCl) was maintained. From the measured pH the pD of the samples was calculated from: pD - pH + 0.4.’ The values for 13C chemical shifts G(ppm) obtained with tetramethylammonium chloride as internal standard were converted to the TMS scale by adding 56.5 ppm to each value. Determination of stability and protonation constants by potentiometric titrations. A vessel with a capacity of 50 cm3, thermostatted at (25.0 + 0.2)‘C was used for the potentiometric titrations. The vessel’s cap was equipped with inlets for the two electrodes, the burette and the nitrogen flow. Titrant (0.2 moldme NaOH) was added from a 2.5cm’ automatic burette with an accuracy of volume addition of f 0.003 cm3. The solution was stirred during the titration with a magnetic stirrer in addition to being blown through by the nitrogen stream. The ligands, converted into the protonated form by adding a standard HNO, solution in excess, were titrated in the absence (protonation constants) and in the presence (stability constants) of metals. The concentrations of metals in titration

samples varied (ligand to metal ratios were 1: 2, 1:4, 1:6, 1:8, 1:lO and 1:20). A constant ionic strength of 0.35 (KN03) was maintained during the measurements. The measured pH values were converted into the hydrogen ion concentrations according to Irving et al.” The protonation and stability concentration constants were calculated on a Univac 1110 computer at the Zagreb University Computing Centre using the Miniquad programme.” UV/VIS spectrophotometric measurements. The UV spectra of aqueous ligand solutions were taken at various pH values. Bathochromic shifts were observed with decreasing pH of the solutions (Fig. 3). The UV/VIS spectra of ligands and complexes taken in the methanolic medium are summarized in Table 1. The modified continuous variation method of Job’* and the molar ratio method of Yoe and Jones,i3 were both pursued throughout in determining the ligand to metal ratio. The apparent stability constants were calculated from the data obtained by the continuous variation method using the programme of Likussari4 and the PDP-8/E (058/10Syst.) DEC computer. RESULTS AND DISCUSSION Protonation equilibria of liganh Three well separated inflections in potentiometric titration curves of ligands I, II and III (Fig. 1) prove that all ligands have three protonation steps. However, it was possible to calculate with sufficient precision only the tist two

Tablel.UV/VISspectrophotometric dataforligandsI,lI andIIIanda series ofmetai complexes inthemethanolic medium Compound Ligand I Cu(II)-oomplex Co(II)-complex Pi(II)-oompler Zn(II)-complex Ll&etnd II Cu(II)-complex I&and III Cu(II)-oomplex Co(II)-complex Zn(II)-uomplex

h_/Juu

660(42) ; 52O(eh.) ; 59N7.2) ;

660(35) i

660(53) i SlO(eh) ;

( c_,

305(5.8*103)~240(8.6*X?); 207(1.2*104) 341(4.5*X+); 258(7.2*&; 217(4.4*103) 350(1.0*104);260(1.6*104);218(1.8*104) 348(1.1~102);262(2.5*102) 330(7.1*102);271(6.0*102);258(5.3*102) 299(4.6*103)s240(6.6*103)i207(1.3*104) 331(3.3*103);258(6.0*103))218(4.6*103) 297(5.7*103);240(7.6=103);207(l.3*104) 330(5.6&)~ 258(8.0*103);214(6.2'103) 346(1.3*104);260(l.8*104);215(2.3*104) 324(1.1'103)~258(l.4*103)

262

Z. CIMERMAN

6.0

PH 6.0

2.0

1.0

1.5

2.0

VN~OH (Cm’)

Fig. 1. Potentiometric titration curves of a 5.00 x low3 mol drne3 solution of ligand I alone and in the presence of metals. Each curve represents the mean value of 2-4 consecutive titrations.

constants (Table 2). The values of the third constant were too low to achieve the reliability range with the concentrations (5 x 10e3 mol dm-’ solutions) applied. According to the literature data for amino- and aminomethyl-pyridines’ the first constant was tentatively assigned to the protonation of the 3-aminomethyl group and the second constant to the protonation of the ring nitrogen. As experimental evidence for presumed protonation equilibria of ligands, the protonation constants of particular functional groups of ligand I were determined by 13Cnuclear magnetic resonance spectrometry. Assignment of aliphatic carbon atoms and the C-5 aromatic carbon atom was performed on the basis of the one-bond carbon-proton couplings

protonation

and z. STEFANAC

observed in the undecoupled spectra. The remaining four aromatic carbon atoms were preliminarily assigned using the literature data for chemical shifts of structurally resembling monosubstituted pyridines.‘5-‘7 A significant effect of substituents in positions 3, 4 and 6 of the pyridine ring was not expected, since in all cases aliphatic groups are bound straight to the ring. Carbon-proton couplings through two andlor three bonds to 5-H as well as to protons of aliphatic groups confirmed the assignment of aromatic carbon atoms. The chemical shifts, splitting patterns, coupling constants and assignment of the ‘%ZNMR resonances of ligand I at pD 11.5 are summarized in Table 3. The pD dependence of the chemical shifts is shown in Fig. 2. A decrease in pD from 11 to 8 is accompanied by upfield shifts of C-3 and 3-CHz resonances, indicating protonation of the 3-aminomethyl group.” As the pD decreases further, the resonance pattern of all ring carbon atoms significantly changes. Signs and AS amounts roughly correspond to those noted for the protonation of the pyridine, except in the case of C-5 where a small upfield shift is observed.” The differences in the range 1 < Ad < 5 ppm can be explained if the number, the nature and arrangement of substituents are considered. Thus, changes in the spectra of ligand I in the pD range from 8 to 4 can be reasonably ascribed to the protonation of the ring nitrogen. Further decreasing of pD down to 0.1 changes insignificantly the 13CNMR spectra. It is obvious that extremely acidic conditions are necessary for the protonation of the 2-amino group of ligand I. This is in accordance with very weak basicity of the amino group observed for 2- and 4-monoaminopyridines, as well as with the resonance equilibria presumed by Albert for monocations.’ Charge delocalization over both nitrogens, in the manner of an amidinium cation, effectively prevents addition of the second proton. Logarithmic values of protonation constants K, and Kz determined graphically from the plot 6vs pD are 6.3 and 9.4, respectively.

Table 2. Protonation constants of the ligands determined by potentiometric titration in aqueous solution at (25.0 f 0.2)“C!, I = 0.35 (KNO,) K+D.

log K$S.D.

log fi2'S.D.

I

8.g59~0.002

5.778f;o.o04

14.737’0.003

II

8.96450.002

5.407+0.004

14.371-+0.003

III

9.141~0.001

6.604-+0.002

15.745'0.002

Ligfwld

log

Protonation equilibria and complex formation ability of 2-amino-3-aminomethyl-4,6-disubstituted

pyridines

263

Table 3. Chemical shifts, splitting patterns and coupling constants in the ‘%NMR spectrum of Iigand I by pD 11.5 Splitt* (coupling

Chl3OliCal

shirta,

$ms

J,

(PPd

23.66 37.00

pattern constant

quartet (127.0)

Aeei@Wnt

Hz )

6-(X3

doublet (-2)

triplet

3-2

(136.7) 59.13 72.28 115.56 117.66

147.73 156.40 157.91

quartet (142.8)

triplet

triplet

quartet

doublet

(144.0)

(WV51

( M5)

doublet

quartet

triplet

063.6)

(-4)

(u4)

triplet

doublet

triplet

C-5)

(@5)

(-5)

triplet

triplet

( M4)

(d4)

quartet

doublet

( d6)

( r2)

4-CH3

C-4) 4-a2

c-5 C-3

C-4 c-6 c-2

triplet ( N4)

reeolutloIl of 1.2 HI makes unobtainable distinct multiplete In oases of eunall aoupling con&ante.

The digital

The potentiometrically determined values for the protonation constants of ligand I (Table 2) differ from the values obtained by ‘%Z NMR by 0.5

logarithmic units in the case of K, and by 0.4 logarithmic units in the case of K2. These deviations may be expected, since the potentiometric titrations were done in H,O, and the NMR measurements in DzO? Additional reasons for the disagreement of the corresponding results are different ionic strength, concentrations and temperatures of solutions measured by both methods. As the thermodynamic corrections were not accomplished it has to be called to mind that the potentiometric concentration constants are compared with spectrometric mixed constants. The correlation of protonation constants of ligands I, II and II (Table 2) shows differences in basicity between the ligands, being more explicit in the case of the second constant related to the protonation of the heterocyclic nitrogen. The

basicity of ligands decreases in the order ligand III > ligand I > ligand II. The influence of the 4- and 6-substituted groups on the basicity of the ring nitrogen is also evidenced from the UV spectra. Decreasing pH in the range of the protonation of the ring nitrogen causes bathochromic shifts of the lower energy transition maxima by all ligands according to the behaviour of 2aminopyridines. *’ The plot of A,, vs pH (Fig. 3) shows the same sequence of the ligands’ basicity decrease as the potentiometrically determined constants. The log K, values obtained are merely comparable with the one cited for the primary amino group of 3-aminomethylpyridine as pK, 8.04 being very

likely only an approximate value.’ The explanation for the differences of log K, within the series of ligands I, II and III has to be ascribed to the nature and arrangement of additional substituents on the pyridine ring. Their base-strengthening or base-

Z. CIMERMAN

I

a

and Z. STEFANAC 158 156

152 60

---0-150

58 118

d@prd

b(ppm) 1 146 I

36 3&

c-3 c-5

Fig. 2. pD dependence of the ‘F chemical shifts of ligand I: (a) resonances of aliphatic carbon

atoms; (b) resonances of aromatic carbon atoms. weakening effects are more evidently reflected by the differences in log K2 values related to the proton uptake by pyridine nitrogen. The specification of the net result and the symbol of the mesomeric and inductive effects of the methyl, aminomethyl and methoxymethyl substituents with regard to their positions as well as a potentially evoked steric hindrance of the latter in the Bposition is inaccessible. Therefore the log K2 values of the studied ligands cannot be meaningfully correlated either with one another or with the data from the literature for the pyridine bearing the very same remaining two substituents, i.e. amino and methyl group.

295..

290:

6

6

8

io

12

PH

Fig. 3. pH dependence of UV absorption maxima of ligands: I (O), II (A) and III (0).

Complexes with Cu(II), Ni(II), Zn(I1) and Co(I1) In solution complexes of ligands I, II and III with Cu(II), Ni(I1) and Zn(I1) are formed immediately. The formation of complexes with Co@) is very slow at room temperature. The complex formation is affected by the pH of the solution (Fig. 4). A significant increase of ligands’ complexation ability is observed by increasing pH in the range 5 < pH < 7 with optimal conditions for complex formation about pH 2 8. The conditions mentioned before are valid for aqueous and methanolic media.

Protonation equilibria and complex formation ability of 2-amino-3-aminomethyl-4,6-disubstituted

pyridines

265

ligand I with Zn(I1) simultaneous presence of the 1: 1 species is observed. The equilibrium of 1: 1 and 2: 1 species is most probably the reason for high relative errors obtained for apparent stability constants of Cu(I1) complexes. Judging from apparent constants determined by UV spectrophotometry (Table 4), the stability of 2:l complexes decreases in the order Co > Ni > Zn. Potentiometric stability constants (Table 5) for all studied complexes could not be determined because of a very low formation rate of Co(I1) complexes. In some systems precipitation took place during titration. Since the data could only be taken before the start of precipitation, the number of data was sometimes insufficient to attain good precision [in the case of ligand I and Zn(II)]. Table 5 illustrates that the stability of the complexes decreases following the sequence Cu > Ni > Zn. It Fig. 4. Effect of pH on oomplex formation of ligand I is the usual stability sequence proposed for the complexes of transition metals.21 The inversion of with Cu(I1). [Cu(II)] = 4 x 10e4 mol dm-‘; [ligand II this stability sequence observed by comparing ap1.2 x lo-’ mol dm-‘. parent constants for Co(I1) and Ni(I1) complexes In distinction from 2-picolylamine which forms (Co > Ni) is characteristic of the complexes of 1: 1, 2 : 1 and 3 : 1 complexesz3*6with ligands I, II pyridines, having substituents in a-position to the and III only the presence of 1: 1 and 2 : 1 species heterocyclic nitrogen.” Considering the ligands, the complex stability was evidenced in solution. The ligands bearing the methyl (I and III) or methoxymethyl group (II) in decreases in the order ligand III > ligand the Qosition conform in this respect under- I 1 ligand II. This order indicates a low influence standably to 6-methyl-2-picolylamine which forms of ligands’ total basic strength on the complex unstable strongly dissociated 3 : 1 complexes.’ The stability more effected by the steric hindrance of spectrophotometrically determined ligand to metal the bulky methoxymethyl group positioned in the ratio of the species formed in the methanolic neighbourhood of the coordination sites. solution is 2 : 1 for the complexes of Zn(II), Ni(II) Preparation of the crude complexes was not and Co(I1) (Table 4). In the case of the complex of always successful, although the conditions were Table 4. Ligand to metal ratios and apparent stability constants determined by W

trophotometry in methanolic solutions Complex

h, h)

[Wd]+[~kj (In01dm-3 )

[$&s-d]

Rel.

[Me(II)] log "

i"s"i

341

2.10'4

1:l

4.64

9.06

Ligand I-Co(X)

350

2.10'4

2:l

8.42

5.82

Ligand I-Ifi

348

1.10-2

2:l

5.73

5.94

2:l

5.50

4.17

3.60

4.41

4.50

16.16

I&and

L&and

I-Cu(I1)

I-Zn(II>

330

3.10’3

i 271 331

40lQ-~

i lrl 1:l

Ligand III-Cu(I1) 330

2.10-4

lrl

4.83

12.98

Ligand III-Co(I1) 346

2.10'4

2:l

9.59

7.19

L-d

290-3

2:l

6.65

4.21

Ligand

II-Cu(I1)

III-Zn(I1) 324

spec-

266

z. CIMERMAN

and

z. STEFANAC

Table 5. Stability constants determined by potentiometric titration in aqueous solution at (25.0 zt 0.2)“C, I - 0.35 (KNOs) Ligand

Metal

ion

lo+

,+ S.D.

lo+2

f S.D.

I

0u*+

5.853f0.008

I

lpi*+

3.5620.01

5.8520.03

I

z&l*+

2.93f0.09

5.720.4

II

Cu*+

5.78-0.02

10.10~0.03

Cl&*+

6.5220.01

11.4220.02

III

10.18fO.

01

=

f ‘Phe limited to precipitation

number of obtainable

in the eyetern roraened

carefully checked. Due to easy decomposition of most often very unstable complexes recrystallization had to be avoided and it was not always

possible to obtain pure compounds. Characterization of the prepared complexes by elemental analyses indicated 2 : 1 and 1: 1 ligand to metal ratios, corresponding to the results of the measurements in solution. The results of elemental analyses were confirmed to a certain extent by fast atom bombardment mass spectrometry (FAB) with glycerol used as dispersant.23 In the mass spectra obtained for positive ions, the characteristic distribution of 63Cu and ‘Wu isotopes with the relative abundances of 100 and 44.7% respectively served well to distinguish not only the molecular ions but also a number of copper containing fragment ions. The molecular formulae corresponding to the 2 : 1 ligand to metal ratio were found for copper complexes of ligands I and III with sulphate anion as well as of ligand I with perchlorate anion. -17

425 -

8

-17

408 -

*

391

Cu(ligand I)z 244 -

-17

227

Cu(ligand I) 365 -

-17

Cu(ligand III),

*

348 -

-15

*

expertintal

333

data

due

the preoieion.

214 -

-17

197

Cu(ligand III) The established partial fragmentation pathways were based in addition to the expected isotope peaks pattern also on the presence of several metastables denoted with asterisks in the schemes given above. The mass spectra of nickel and zinc complexes taken under analogous conditions were not amenable to a detailed interpretation. The attempt to elucidate the coordination mode in complejces of the 2: 1 ligand to metal ratio is based merely on the IR spectra taken in the 200-4000 cm-’ region. For interpretative comparison the well documented data on the corresponding complexes of 2-aminomethylpyridine6 and 6-methyl-2-aminomethylpyridine’ have been taken. These compounds behave as bidentate ligands even in the case of the 6-methyl derivative with evidenced influence of a remarkable steric interference. The sterically hindered 2-aminopyridine was also shown to appear as bidentate in nickel complexes containing two molecules of the ligand.7 Presuming that because of the steric arrangement the studied ligands behave as bidentate too, alternative sets of two coordination sites have to be considered: nitrogen atoms of the 2-amino and 3-aminomethyl groups as well as those belonging to the pyridine ring z&d the 2-amino group. More exaggerated changes in the regions of 3000-3500 and 160&17oOcm-’ of the IR spectra of the amino group bearing ligands are caused by association than by coordination. Therefore lower N-H stretching accompanied by higher in-plane

Protonation equilibria and complex formation ability of 2-amino-3-aminomethyl-4,6-disubstituted

bending frequencies than expected for free groups, observed consistently for all investigated complexes has only a limited reliability as an evidence for coordination of nitrogen atoms of both amino groups. On the basis of changes in the 800-200 cm-’ region a far more reliable conclusion could be arrived at supposing that carefully checked assignments of the characteristic bands are submitted. From the isotopic labelling it was possible only to assign by deuteration the band of ligand I at 650 cm-’ (N,N-d2 at 450 cm-‘) as belonging to 3-aminomethyl group out-of-plane bending vibration. In Cu(I1) and Zn(I1) complexes this band of a characteristic broadened shape is shifted to 690 and 675 cm-‘, respectively. In the nickel complex the region is overlapped with one of strong tetraphenylborate absorption bands which are the only bands to be found below 800 cm-’ in this spectrum. The band at 520 cm-’ in the spectrum of ligand I, (505 cm-’ of ligand III) ascribed to CCN skeletal bending vibrations is, as presumed, shifted to 550 cm-’ in copper and zinc complexes. The remaining bands characteristic of the ligand are tot vague even for hypothetical consideration. Thus the bands at 610 and 420 cm-’ in the case of ligand I or at 610 and 410 cm-’ for ligand III assigned to pyridine in-plane and out-of-plane ring deformation are not well defined in the spectra of complexes. Namely, the first band is hidden by absorption of sulphate or perchlorate while the second one appears simply as a weak, broadened deviation of the spectrum curve. It ought to be mentioned however, that no shifts of these bands to higher frequencies have been observed either. As the assignments of bands characteristic of metal-ligand bonds are lacking, the proposal for nitrogen atoms of both amino groups to act as coordination sites appears artificial indeed. But further investigations indispensable as the complement of the insufficient evidence are not feasible with regard to the means at disposal. The absorption bands concerned show the wellknown characteristic differences noted for coordinated as compared to free anions. A very wide band with broad maxima at 1145, 1115 and 1090 cm-’ dominates in the spectrum of Cu(ligand I),(ClO& complex. The emphasized intensity and manifold splitting even if the absorption of the ligands’ ether groups is considered could be interpreted by means of coordinated perchlorate. to However, the absence of the band at 930 cm-’ as well as the fact that a single sharp band is present at 628 cm-’ unambiguously point at the free anion,25 and therefore a four-coordination of copper in the [Cu(ligand I)2](C104)2 complex species.

pyridines

261

The absorption corresponding to the C-O-C asymmetric stretching of ligands I and III is overlaid by a very strong and very broad band at 1170-1070 cm-’ in the spectra of Cu(ligand I)2 and Cu(ligand III), complexes with sulphate. The accompaniment by a strong sharp band at 613 cm-’ complements the pattern characteristic of the free sulphate. Co&idering as more plausible the analogy rather with potentially n-bonding than with a-bonding ligands, e.g. 1,3-propylenediamine, the four-coordination of copper has been assumed.26 Therefore the corresponding complexes have been formulated as dihydrates [Cu(ligand 1)2SO,. 2H20 and [Cu(ligand III)2]S04. 2H20. Shoulders at 1165 and 1145 cm-’ on the very strong, broad absorption band centered at 1110 cm-’ in part appertaining to the ligands’ ether groups as well as the bands of 1070 and 1055 cm-’ joined to the fact that the band at 613 cm-’ is accompanied by an additional one at 650 cm-’ have been taken as evidence for the sulphato complex [Zn(ligand I)2S04]. The positions of bands characteristic of tetraphenylborate in the spectrum of the nickel complex although corresponding to those of the free anion have not been taken as a proof. The presumption of the species [Ni(ligand I),] [(BPhJ2] is based on the light pink colouration congruent with yellow complexes of the four-coordinated nickel with diamines2’ and substituted pyridines.24v28The congruence is extended further to the complexes of the higher coordinated nickel present in solution only. Thus the dissolving of the crude pink complex afforded a light blue acetone and a greenish blue methyl isobutylketone solution. Besides, a solution identical with the latter has been obtained by extraction of a mixture set up for the preparation of the nickel complex with perchlorate as anion. The greenish blue colouration of the extract changed to pink after three days. In addition, the feature of absorption bands due to NH stretching and in-plane bending vibrations of both amino groups resembles the 310&3500 and 1600-1650 cm-’ regions of the complex Cu(ligand I)z(ClO4)2 with presumably four-coordination of the metal. authors are indebted to Professor J. Seibl, ETI-IZentrum Ziirich, for taking the mass spectra and helping with interpretation and to Dr. Z. MeiC, Institute R. Btikovib, Zagreb, who kindly made recording of the ‘)C NMR spectra possible. Special thanks are due to members of Institute for Medical Research and Occupational Health, Zagreb, Professor VI. Simeon for useful suggestions concerning the determination of the potentiometric constants and to Z. ICralj for immediate help with computation. Acknowledgements-The

268

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