DISCUSIÓN 69

D egradation Products

3.1

Introduction

During the course of the preparation of series of second generation poly(pyrazolyl)borate complexes (Chapter 2) it was realised that the ligand was often thermodynamically unstable and had a tendency to undergo degradation, even if the utmost care was taken to keep the reactions conditions mild. Indeed this instability has previously been reported in the literature.^*^’^^’’®^ Several unexpected products have been isolated, either as side products or as part of a deliberate syntheses. A discussion of their characterisation and some speculation as to their origin is the subject of this Chapter.

3.2

Novel 7/^/^r<?scorpionate’ complexes

It has already been pointed out that the isolation of compound [8] in very low yields can be attributed to the degradation of the poly(pyrazolyl)borate ligand. Since in the preliminary attempts at preparation of [8] the successful isolation o f the complex was the main priority, any side products were initially discarded. Later it was realised that the degradation of [8] occurred not only during the reaction but also during work up procedures. This was intriguing and we decided to investigate the phenomenon. Careful monitoring indicates that suspension of [8] in an ethanolic solution for several days leads to formation of a new compound. The 'H NMR spectrum (Figure 3.1) of this product consists of six signals, 6 6.53, 5.92, 4.22, 2.57, 2.21 and 1.21 ppm. While singlets at 5 5.92, 2.57 and 2.21 ppm can be readily assigned to the 3,5- dimethylpyrazolyl groups (down field shift of + 0.43 M e\ +0.38 and +0.24 ppm Me^ when compared with the starting ligand K[HB(3,5-Me2Pz)3]), the quartet and the triplet

D egradation Products

signals at 8 4.22 and 1.21 ppm, respectively, result from the presence of an ethoxide group. The signal for the 7i-coordinated benzene appears at 6.53, a shift o f +0.17 ppm compared with [8]. PF Ru BH N N

J

Me

C H z

JL

ULa^

CH

TP* 1 M I I r i ' T T I I { I I I - n I I M I I I 1 I I I I i I T | I N I I I ! I I [ I I I I I I I M I I I I € 5 4 3 2 1 PPM Figure 3.1 ’H NMR spectrum of [20].

Comparison with the chemical shift positions of the ethanol molecule (8 3.56 and 1.11 ppm), along with the analysis o f the integrals, allows formulation o f the new compound as a novel /leteroscorpionate, [Ru(r|^-C6HJ (K^-A^A(,0-HB(3,5-Me2Pz)2(0CH2CH3)} ] [PF,] [20] (Figure 3.2).

D egradation Products Ru -I- Me Me CH, CH Me Figure 3.2 [Ru(r|"-CA){K'-A^,MO-HB(3,5-Me2Pz)(OCH2CH3)}in [20]

The ’^C NMR spectrum of compound [20] is similarly uncomplicated (Figure 3.3). Whilst the signals at Ô 153.33 C \ 143.54 108.61 C \ 16.11 Me" and 11.85 ppm Me", are due to the 3,5-dimethylpyrazolyl groups of the Ag/emscorpionate ligand, the signals for the benzene ligand appears at 5 83.33 ppm. The signals for the coordinated ethoxide group appear at ô 73.18 and 14.97 ppm.

C" /CH .0, Ru. N N [Me3 Ç4 Mes > 111' I I111 n 11 i 1 1 1 1 1 1 IT 1171 1 1 1 1 1 1 1 1 r f 11] 1 III 111 N 11 i II j M n 11 m 11 i i I I' H i 11 140 120 100 80 60 4 0 20 PPM Figure 3.3 '"C NMR spectrum of [20].

D egradation Products

The FAB mass spectrum o f [20] consists of an envelope at m/z 475 that can be attributed to The infrared spectrum exhibits absorptions that are consistent with the presence of the aromatic ligands together with absorptions at 2447, 1580 and 844 cm % due to the v(BH), v(C=Ncj,docyciic) v(PFJ stretches respectively. The absorption for the B-H bond is unchanged from the free ligand value, and it is interesting to note that a negligible difference is also observed for other complexes with coordinated poly(pyrazolyl)borates {e.g. +9 cm ' for [13]) and contrasts with the large differences o f ca. +127 cm ', between the free ligand value and that for the tris chelated ligands in [8]. Scheme 3.1 shows a possible mechanism that leads to the formation of

[20]. It is reasonable to speculate that when suspended in ethanol the boron in [8] experiences an initial attack from ethanol.

The attack o f the ethanol results in a concomitant rupturing of one of the B-N bonds and consequent formation o f an equilibrium between intermediates (1) and (2). While in (1)

the proton residing on the oxygen atom of the ethoxy 1 group forms a hydrogen bonding interaction with the endocyclic nitrogen atom of the ‘dislocated’ pyrazolyl group, in (2), the proton is abstracted from the ethoxyl group by the 3,5-dimethylpyrazolyl ligand. A final attack of the ethoxide on the ruthenium centre leads to the permanent ejection of the pyrazolyl group from the coordination sphere and the formation of a bridging ethoxyl group, between ruthenium and boron.

D egradation Products --- Ru HOEt Me. Me, [8] Mes a OEt Me: Me, '5 + + J z * ) Ru BH CH + (1) (2) [20] + S^S-M e^PzH

D e g ra d a tio n P ro d u c ts

In order to demonstrate that [20] can be prepared independently, the dimer [{Ru(t]^-

€61^6)0 1 2)2] was suspended in ethanol and subsequently reacted with K[HB(3,5-

Me2Pz)J. After stirring for 2 hours the reaction mixture was worked up with NH^pFg]

and purified to give [20] as an orange/red powder in 72 % yield. A similar procedure

designed to convert the free ligand K[HB(3,5-Me2Pz)J into K[HB(3,5-

Me2Pz)2(OCH2CH3)] leads to complete degradation of the starting material and

consequent formation o f 3,5-dimethylpyrazole.

A related attack on the boron in a (pyrazolyl)borate ligand by a ketone has been shown to take place m/rnmolecularly in [Mo(K^-H2B(3,5-Me2Pz)2}(CO)2(PMe3)(r|^-C,0- Me(H)C=0)], to give a complex in which the acyl functionality inserted into one of the B-H bonds (Figure 3.4).'"" H — c- Me N - PMe .

n-„>/

3 h, 70 OC PMe

Figure 3.4 Intramolecular attack of an r\^ coordinated aldehyde on the 6zj(3,5-dimethylpyrazolyl)borate ligand.

Unequivocal proof of the identity o f [20] as a novel /ze^emscorpionate complex is obtained by carrying out an X-ray diffraction experiment. The crystal structure of the cation in [20] is shown in Figure 3.5.

D egradation P roducts rs Rui CK C?7 Pz ;i7

Figure 3.5 The cation [Ru{^^-C,n,){K^-N,N,0-m{3,5-MQ,?z)(0CH,CH,)}Y in [20].

D egradation Products

The ruthenium atom exists in a distorted octahedral geometry, sandwiched between a benzene molecule and the /ze^emscorpionate ligand [HB(3,5-Me2Pz)2(OCH2CH3)]'. The R^-Qrene bond Icngths range from 2.164(11) Â for Ru-Cl to 2.190(11) Â for Ru-C5 (average bond length o f 2.175(11) Â), with a separation between the ruthenium atom and the arene plane of 1.69 Â. These bond lengths are considerably shorter than those displayed by [8], (2.208(8) and 1.719 Â respectively) and this can be attributed to the three 3,5-dimethylpyrazolyl groups exerting greater steric crowding at the ruthenium centre than the crowding achieved by the ^e/croscorpionate ligand in [20].

Alleviation o f the congestion around ruthenium upon replacement o f the third 3,5- dimethylpyrazolyl group with an ethoxide group is further demonstrated by the shorter Ru-N distance of 2.106(7)

A

(average). Although this bond distance is smaller than that observed in [8], 2.180(8)

A,

it is comparable with that reported for [Ru(k^-HB(|li- H)(3,5-Me2Pz)2}(H)(n '-COD)],'"" 2.118(2)

A.

The ethoxide group of the /ze/eroscorpionate ligand is linked to the ruthenium with a Ru-01 bond distance of 2.123(6)

A,

similar to that reported for the p-OMe group in [(T|'-C6H JR u(p-0 Me)3Ru(Ti'-CA)][BPhJ,"° 2.106(8)

A.

The bite angles of the

tridentate ligand range from 82.1(3) ° for N12-Ru-N22 to an average value of 77.5(3) “ for N-Ru-01. The closer approach of the new ligand to the ruthenium atom is mainly achieved through the reduction of the steric congestion, the largest bite angle in [20] contrasts with those displayed by the poly(pyrazolyl)borate ligands in the less tightly bound [8] and [19] [86.1(3) and 85.4(5) ° respectively].

D egradation Products

In sp e ctio n o f the cation in [20] d o w n the axis (F igure 3.6) rev eals th at although the o x y g en atom is projected b etw een the carb o cy clic C 1-C 2 bond, the ethyl group o f the eth o x id e approaches P z' (3,5-M e2Pz) m ore closely, w ith a R u -B -0 1 -C 7 torsional angle o f 143.8 \ It is also notab le that the py razo ly l groups tw ist aw ay from the plane d efin ed by R u - B - N l l and R u -B -N 2 1 , by 6.26 and -4.78 ° respectively. In com plexes such as [8] and [19] the pyrazo]yl groups dev iate aw ay from the an alo g o u s p lan es by no m o re than 2 It is also n o tab le that the Q , sy m m etry o f the ‘[R u{H B (3,5-M e2Pz)3}]” frag m en t in [8] is no longer presen t in [20]. T his is m anifested in tiltin g o f th e '6 /j(3 ,5 - d im e th y lp y ra z o ly l)’ fram ew ork aw ay from the axis d efined by the centro id -R u -B vector (1 6 0 .7 "). A s a direct co n se q u en ce o f this tilt the p yrazolyl groups ap p e ar to be eclipsed o v e r the aren e carbon atom s C 4 and C5. In direct co n trast the py razo ly l fram ew ork in [81 and [19] adopts a perfectly staggered co n fo rm atio n over the arene.

C 8

. . . C 2

C3

N 21

C 4

Figure 3.6 T he catio n in [20] v iew ed dow n Ru°°°°°B axis.

D egradation Products

In an attempt to extend the synthesis described for [8] (Section 2.3) to complexes incorporating bulky arenes the dimer [{Ru(r|^-l,2,4,5-Me4C6H2)Ci2}2] was reacted with K[HB(3,5-Me2Pz)3] in acetonitrile. Work up of the reaction mixture from a methanolic solution o f NH4[PFJ however resulted in deposition o f a wide range o f products that

have not been identified. Although various attempts were made to separate the products these were generally unsuccessful. Attempts to crystallise the products from different solvents led to isolation o f a small number of single crystals. An X-ray diffraction study of one these crystals revealed a new complex, [Ru(r|^-l,2,4,5-Me2C6H2)(3,5- Me2PzH){K'-HB(3,5-Me2Pz)2(OMe)][PFJ [21] (Figure 3.7).

In compound [21J the ruthenium is in a distorted octahedral geometry. In addition to being 7t-bonded to 1,3,4,5-tetramethylbenzene (durene), ruthenium is also bound to a bis chelating hydride6z5(3,5-dimethylpyrazolyl)(methoxyl)borate ligand and a monodentate 3,5-dimethylpyrazole ligand. The Ru-C bond lengths to the durene range from 2.191(6) to 2.255(5)

Â

(average length of 2.229(6)

A),

with a separation between the arene plane and the ruthenium atom of 1.723

A.

Whereas the bond lengths between the aromatic carbons and the methyl substituents, in the durene, do not deviate much from the average value of 1.50(1)

A

the carbon-carbon bond lengths within the ring vary to an extent such as to be consistent with a significant degree of bond fixing [short. C2-C3 1.395(8), C4-C5 1.397(9), C6-C1 1.402(8)

A;

long: C1-C2 1.432(8), C3-C4 1.427(9), C5-C6 1.436(9)

A].

D egradation Products

Pz

\cm

Figure 3.7 The cation in [Ru(r)‘-l,2,4,5-MejQH,)(3,5-Me,PzH){K'-HB{3,5-Me,Pz), (OMe)][PFJ [21], with atomic numbering.

D egradation Products

It is interesting to note that although the ^w(3,5-dimethylpyrazolyl) framework approaches the ruthenium with an average Ru-N bonding distance o f 2.092(5) Â the monodentately coordinated 3,5-dimethylpyrazole binds to ruthenium with a longer bond, 2.135(5) Â. While in comparison to the pyrazoles in [Ru(Pz)2(PzH)3DMSO],^*

Ru-N 2.087(6) Â, the monodentately coordinated pyrazole in [21] appears loosely bound. However, comparison with [Ru(H)(CO)(PPh3)2CI(3,5-Me2PzH)],‘' ‘ 2.174(8) Â, implies the bonding interaction is relatively strong.

The elongated bond between ruthenium and the unidentate 3,5-dimethylpyrazole can be rationalised on the basis of strong steric repulsion existing between the methyl substituents on the durene and the pyrazolyl ligand. Close approach o f the endocyclic nitrogen atoms of the ‘èwpyrazolyl’ ligand is facilitated by tilting of the èwpyrazolyl fragment away from the axis, defined by the centroid°°°°‘’Ru“°°°“B vector. Although the bite angle o f the /zaremscorpionate ligand, 85.8(2) °, is considerably larger than that displayed in [20], 82.1(3) °, it is similar to that exhibited in [8], 86.0(3) °. The B-N bond lengths [B -N ll 1.55(1) and B-N21 1.56(1)] are comparable to those observed in both [20], average value of 1.53(2) Â and [8], 1.51(1) Â.

The transformation of the [HB(3,5-Me2Pz)3]' ligand into a Aaramscorpionate [HB(3,5- Me2Pz)2(OMe)]‘can be rationalised as before on the basis of Scheme 3.1. It appears that

in contrast to [20] in which the third pyrazolyl group is completely replaced by an alkoxide function (OEt ), during the formation o f [21] the attack o f the methanol molecule leads to the rupturing of the B-N bond but then stops at the stage of intermediate (2). At this stage the proton, originally on the methanol molecule is

D egradation Products

transferred onto the monodentately coordinated 3,5-dimethylpyrazole ligand. Although [21] was isolated as a minor component of a complex mixture its identification by X-ray crystallography strongly reinforces the proposed mechanism in Scheme 3.1. The fact that the methoxide does not bind to the ruthenium centre allows for a shorter B -0 bonding distance, 1.429(9) Â), than that seen in [20], 1.486(13) Â.

It is also notable that the unidentately coordinated 3,5-dimethylpyrazolyl group resides in a quadrant that is structurally trans with respect to the methoxide group. This is not all that surprising considering that the attack on the boron atom by the alcohol group represents a 8^2 type of nucleophilic substitution, as depicted in Scheme 3.2.

r

1

Nu

_X

r 2

r3

r4

Nu

R

Scheme 3.2 8^,2 type nucleophilic attack on a central X atom.

The attack o f the nucleophile on to central atom X leads to formation o f a intermediate species which is very similar to (2) in Scheme 3.1. The simultaneous removal of R^, which is trans to the nucleophile, leads to inversion of the configuration at X and the formation o f X(Nu)(R’)(R^)(R'‘). Similarly in the attack of the methoxide on the [HB(3,5-Me2Pz)J ligand, R’ can be considered to be a hydride, X(R^)(R'*) the B(3,5- Me2?z)2 fragment, and R^ the 3,5-dimethylpyrazole leaving group.

D egradation Products

3.3

Reactions of [{R

u

(

t

]^-C6H6)C12}2] with methyl^r/s(3,5-dimethyl

pyrazolyl)silane

In Chapter 2 it has already been demonstrated that neutral second generation poly(pyrazolyl)methanes, such as HC(3,5-Me2Pz)3, are very robust ligands, in contrast to the anionic boron centred derivative [HB(3,5-Me2Pz)3]’. In order to investigate this further the neutral silyl analogue, MeSi(3,5-Mc2Pz)3, was reacted in an acetonitrile solution with [{Ru(r|^-C6H6)Cl2}2] over several hours. However, contrary to

expectations the ligand underwent decomposition to yield a half sandwich complex. It was originally thought that the isolated product was the previously reported [Ru(r|^- C6H6)(3,5-Me2PzH){K^-HN=C(Me)3,5-Me2PzH}][PF6]2.^^ However the microanalytical data are consistent with the presence o f only one [PFô]’ anion. The ^H N M R spectrum o f the isolated product displays only one set o f 3,5-dimethylpyrazolyl signals (ô 2.76 Me^, 6.53 H^ and 2.70 ppm Me^) as does the N M R the spectrum (Ô 163.84 C^, 20.38 Me^, 146.73 C^, 158.63 and 15.70 ppm Me^). The signals for the coordinated benzene appears at ô 6.10 ('H N M R ) and 86.56 ppm ( ’^CNM R). In addition to these signals the

’H N M R spectrum also contains an extra methyl signal at ô 2.95 ppm. However the

N M R spectrum displays two additional signals, ô 114.21 and 13.71 ppm. From analysis

o f the integral ratios of N M R signals as well as the microanalytical data it is possible to formulate the product as [Ru(r|^-C6H6)Cl{K^-NHC(Me)=(3,5-Me2Pz)}][PF6] [22] (Figure 3.8) The infrared spectrum o f [22] consists of distinct absorptions at 3346, 1648, 1570 and 843 cm"^ due to v(N -H ), v(C=Nexocyciic), v(C=Nendocyciic) and vfPFe) respectively.

D egradation Products

+

Figure 3.8 [Ru(n''-QHJCI(K'-NHC(MeM3,5.Me;Pz)}][PFJ (221

The identity of [22] was unequivocally confirmed by X-ray diffraction. The X-ray structure of the cation in [22] is shown in Figure 3.9. In addition to being bonded to the carbon atoms of the benzene ligand (average Ru-Ca^^e 2.14(3)

A)

the ruthenium atom is also bonded to a chloride ligand, with a bond length o f 2.412(5)

A,

very similar to the previously observed value in [15], 2.397(2) and [17], 2.415(2)

A.

An additional bis chelated ligand that has resulted from the condensation of a 3,5-dimethylpyrazolyl group and an acetonitrile molecule [(NH-C(Me)=(3,5-Me2Pz)] is formed and bonds to the ruthenium in a bidentate coordination mode. The coupling of 3,5-dimethylpyrazole groups with unsaturated nitrile molecules such as RCN to yield ‘ruthenium(amidine)’ derivatives has previously been commented on.'°^’"''"^ ’

D egradation Products Cl C2 $ 0 3 0 5 04 Ru i \ 1 1 0 3 1 0 2 4 0 2 6

F ig u r e 3.9 C rystal stru ctu re o f cation [R u(r|C C (,H JC l{K C N H C (M e)=(3,5-M e2P z)}] in [22J.

D egradation Products

While the endocyc]ic nitrogen atom o f the new bidentate ligand approaches the ruthenium centre with a Ru-N bond o f 2.01(2) Â the amidine nitrogen does so with a longer Ru-N bond o f 2.07(1) Â. The Ru-N bond lengths are much smaller than those reported for [Ru(CO)(CH=CHCMe3){NH=C(Me)(Me2Pz)}PPh3][PF6], (2.180(2) and 2.113(6) Â) and the relative order o f bond length is reversed in the two complexes. Initially it seemed surprising that [22] should contain a [PFô]' anion at all, since it was expected that the his chelating ligand and the chloride would balance the charge on the ruthenium(II) ion. The presence o f a [PFe]’ anion can only be justified if the bis chelated ligand is neutral. Inspection o f the bond lengths in that ligand reveal that the N12-C31 bond length in [22], 1.19(4) Â and must correspond to a double bond. In contrast the amidine complexes reported by Romero et. it is the corresponding C31-N1 bond length that approximates to a double bond.^^"* This has the implication o f rendering a positive and a negative charge on N12 and N1 respectively. The presence o f an acidic proton on the coordinated endocyc\dc nitrogen atom results in no net charge on the bis chelated amidine ligand.

C hapters: Experimental

3.4

Experimental

Details o f Instrumental methods used and the starting materials prepared are as described in Section 2.6. The ligand MeSi(3,5-Me2Pz)3 was kindly supplied by Dr. A. Sella.

[Ru(Ti'-C,H,){K'-A,A,0-HB(3,5-Me2Pz)2(OCH2CH3)][PFJ [20]

The compound [(Ru(r)^-C6H6)Cl2}] (0.172 g, 0.34 mmol) was suspended in degassed

ethanol (96 %, 25 cm^) and stirring for 1 h was reacted with K[HB(3,5-Me2Pz)3] (0.242 g, 0.72 mmol) for 3 h. The solution was filtered through celite and treated with ethanolic NH4[Pp6] (excess). Reduction in volume followed by cooling at 0°C led to deposition of

[20] as red crystalline material. Yield: 0.0279 g, 0.49 mmol, 72 %, (Found: C, 38.4; H, 4.6; N, 9.7. Calc, for C,gHz^N^B,O,F^P,Ru, : C, 38.9; H, 4.7; N, 10.1) Mass Spectrum (m/z): 427 Infrared: v(BH) 2447, v (C = N ,,j^ ,J 1580, v(PFJ, 844 cm '.

[Ru(Ti'-C,HJCI{K'-NHC(Me)=(3,5.Me2Pz)}][PFJ [22]

The compound [{Ru(ri'’-C6H6)Cl2)] (0.0782 g, 0.164 mmol) was dissolved into degassed

acetonitrile (25 cm^) and subsequently transferred to a Schlenk tube charged with MeSi(3,5-Me2Pz)3 (0.115 g, 0.35 mmol). After stirring for 2 h the solution was evaporated to dryness and the residue extracted into methanol and then treated with N H [PFj (excess). Compound [22] precipitated as a yellow crystalline material which was filtered off. Yield: 0.0931 g, 0.27 mmol, 81 %, (Found: C, 31.0; H, 3.3; N, 8.1. Calc, for C,3H,7N3F6P,Ru, : C, 31.4; H, 3.3; N, 8.5). Mass Spectrum (m/z): 317 [M-PF^-

Cl f . Infrared: v(N-H) 3346, v(C=Ne,ocyciic) 1648, v(C=Ne„docyciic) 1570, v(PFJ 843 cm '.

C hapter 3: Experimental

3.5

Crystallography

General crystallographic procedures are described in Section 2,7.

i) [Ru(Ti‘^-C,H,){K^-A^,7V,0-HB(3,5-Me,Pz),(OCH2CH3)][PFJ [20],

Q ystal data:- CigHg^BiF^N^OiPiRu,, M = 571.28 g mol % monoclinic, space group P2./C, a = 7.957(1), b = 20.49(6), c = 14.292(6) Â, p = 91.29(3) \ U = 2330(1) Â' (by least-squares refinement of diffractometer angles for 26 centred reflections in the range of 12 < 20 <24 °), Z = 4, F(OOO) = 1152, = 1.629 g cm '\ p = 8.07 cm ’, red crystal, 0.65 X 0.54 X 0.78 mm.

T h e CO-20 technique was used to measure 4902 reflections (3999 unique) in the range of 5°<20<50°. The structure was solved by the conventional direct methods and developed by using alternating cycles of least squares refinement and difference-fourier synthesis. The final cycle of least squares refinement included 283 parameters for 3999 variables and did not shift any parameter by more than 0.001 times its standard deviation. The final R values w e re R = 0.0707, R^ = 0.170 {for data with I>2ct(I), based on F) and R = 0.102, R^ = 0.206 (for all unique reflections, based on F^), and the final difference-Fourier was featureless with no peaks greater than 1.3 eA'\

ii) [Ru(r|'-l,2,4,5-Me,C,H2)(3,5-Me,PzH){K"-HB(3,5-MejPz)2(OMe)][PFJ [21]. O ystal data:- ,F^NgO,P|Ru,, M = 709.49 g mol ’, monoclinic, space group P2,/c, a = 9.063(2), b = 18.899(5), c = 17.847(4) Â, P = 90.16(2) \ U = 3057(1) A" (by

In document Estudio de la interacción del virus de Zika con proteínas de membrana celular (página 69-74)