Metal-promoted synthesis of amidines containing the model nucleobases 1-methylcytosine and 9-methyladenine

Article abstract of DOI:10.1039/c1dt10638d

The amidine complexes cis-[L₂PtNHC(R){1-MeCy(-2H)}]NO ₃ (R = Me, 1a; Ph, 1b, Me₃C, 1c; Ph₂(H)C, 1d) and cis-[L₂PtNHC(R){9-MeAd(-2H)}]NO₃ (R = Me, 2a; Ph, 2b; Me₃C, 2c; Ph₂(H)C, 2d), are formed when cis-[L ₂Pt(μ-OH)]₂(NO₃)₂ (L = PPh ₃) reacts with 1-methylcytosine (1-MeCy) and 9-methyladenine (9-MeAd) in solution of MeCN, PhCN, Me₃CCN and Ph₂(H)CCN. Reaction of 1a,b and 2a,b with HCl affords the protonated amidines [NH ₂C(R){1-MeCy(-H)}]NO₃ (R = Me, 3a; Ph, 3b) and [NH ₂C(R){9-MeAd(-H)}]NO₃ (R = Me, 4a; Ph, 4b) and cis-(PPh₃)₂PtCl₂ in quantitative yield. Treatment of 3b and 4b with NaOH allows the isolation of the neutral benzimidamides NH₂-C(Ph){1-MeCy(-2H)} (5b) and NH₂-C(Ph) {9-MeAd(-2H)} (6b). In the solid state 3b shows a planar structure with the hydrogen atom on N(4) cytosine position involved in a strong H-bond with the NO₃^- ion. Intermolecular H-bonds between the oxygen of the cytosine ring and one of the H atoms of the amidine-NH₂ group allow the dimerization of the molecule. A detailed analysis of the spectra of 3b in DMF-d₇ at -55 °C indicates the presence of an equilibrium between the species [NH₂C(R){1-MeCy(-H)}]NO₃ and [NH ₂C(R){1-MeCy(-H)}]₂(NO₃)₂, exchanging with trace amounts of water at 25 °C. [¹⁵N, ¹H]-HMBC experiments for 5b and 6b indicate that the amino tautomer H₂N-C(Ph){nucleobase(-2H)}, is the only detectable in solution and such structure has been confirmed in the solid state. The reaction of 5b and 6b with cis-L₂Pt(ONO₂)₂ (L = PPh₃), in chlorinated solvents, determines the immediate appearance of a pale yellow colour due to the coordination of the neutral amidine, likely in its imino form HNC(Ph){nucleobase(-H)}, to give the adducts cis-[L₂PtNHC(Ph) {nucleobase(-H)}]²⁺. In fact, addition of "proton sponge" leads to the immediate deprotonation of the amidine ligand with formation of the starting complexes 1b and 2b. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c1dt10638d

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PAPER
Metal-promoted synthesis of amidines containing the model nucleobases
1-methylcytosine and 9-methyladenine†
Diego Montagner,*a Ennio Zangrando,b Giuseppe Borsato,c Vittorio Lucchinic and Bruno Longatoa
Received 12th April 2011, Accepted 8th June 2011
DOI: 10.1039/c1dt10638d
The amidine complexes cis-[L2PtNH C(R){1-MeCy(-2H)}]NO3 (R = Me, 1a; Ph, 1b, Me3C, 1c;
Ph2(H)C, 1d) and cis-[L2PtNH C(R){9-MeAd(-2H)}]NO3 (R = Me, 2a; Ph, 2b; Me3C, 2c; Ph2(H)C,
2d), are formed when cis-[L2Pt(m-OH)]2(NO3)2 (L = PPh3) reacts with 1-methylcytosine (1-MeCy) and
9-methyladenine (9-MeAd) in solution of MeCN, PhCN, Me3CCN and Ph2(H)CCN. Reaction of 1a,b
and 2a,b with HCl affords the protonated amidines [NH2 C(R){1-MeCy(-H)}]NO3 (R = Me, 3a; Ph,
3b) and [NH2 C(R){9-MeAd(-H)}]NO3 (R = Me, 4a; Ph, 4b) and cis-(PPh3)2PtCl2 in quantitative
yield. Treatment of 3b and 4b with NaOH allows the isolation of the neutral benzimidamides
NH2-C(Ph){1-MeCy(-2H)} (5b) and NH2-C(Ph){9-MeAd(-2H)} (6b). In the solid state 3b shows a
planar structure with the hydrogen atom on N(4) cytosine position involved in a strong H-bond with
-
the NO3 ion. Intermolecular H-bonds between the oxygen of the cytosine ring and one of the H atoms
of the amidine-NH2 group allow the dimerization of the molecule. A detailed analysis of the spectra of
3b in DMF-d7 at -55 ◦C indicates the presence of an equilibrium between the species
[NH2 C(R){1-MeCy(-H)}]NO3 and [NH2 C(R){1-MeCy(-H)}]2(NO3)2, exchanging with trace
amounts of water at 25 ◦C. [15N,1H]-HMBC experiments for 5b and 6b indicate that the amino tautomer
H2N-C(Ph){nucleobase(-2H)}, is the only detectable in solution and such structure has been confirmed
in the solid state. The reaction of 5b and 6b with cis-L2Pt(ONO2)2 (L = PPh3), in chlorinated solvents,
determines the immediate appearance of a pale yellow colour due to the coordination of the neutral
amidine, likely in its imino form HN C(Ph){nucleobase(-H)}, to give the adducts
cis-[L2PtNH C(Ph){nucleobase(-H)}]2+. In fact, addition of “proton sponge” leads to the immediate
deprotonation of the amidine ligand with formation of the starting complexes 1b and 2b.
More recently, the activation of nitriles through coordination to
a metal centre, increasing the rate of the nucleophilic attack at the
Introduction
carbon atom of the CN group,7 led to the synthesis of several
amidine complexes of transition metals, in particular of plat-
inum(II and IV).8 We have recently shown that, if the nucleophile
is the nitrogen atom of the NH2-deprotonated 1-methylcytosine
(1-MeCy) and 9-methyladenine (9-MeAd) (Chart 1), the azamet-
allacycle complexes of platinum(II) cis-[L2PtNH C(R){1-MeCy
(-2H)}]+ and cis-[L2PtNH C(R){9-MeAd(-2H)}]+ (L = PPh3 and
PMePh2) are formed.9,10
They contain as an anionic ligand the deprotonated form of the
N-monosubstitute amidines R–C( NH)NHR’ (R = Me, Ph), in
which the NHR’ group is the nucleobase 1-MeCy or 9-MeAd,
and are structurally similar to 1,3,5-triazapentadienes recently
reviewed by Kopylovich and Pombeiro.11
In this paper we present the synthesis and the structural
characterization of these new amidines, in their protonated
and neutral forms, [NH2 C(R){nucleobase(-H)}]NO3, and NH2-
C(R){nucleobase(-2H)}, respectively. The ionic species are formed
in high yield by protonation of the amidine complexes cis-
[L2PtNH C(R){nucleobase(-2H)}]NO3 (L = PPh3; R = Me, Ph)
with aqueous HCl, allowing the quantitative recovery of the
Amidines, R–C( NH)NH2, their N-mono- and N,N¢-
disubstituted derivatives are important intermediates in the
synthesis of heterocyclic compounds,1 some of which are
pharmacologically active molecules.2 The usual synthetic
methods proceed through: i) addition of metal amides to
nitriles; ii) addition of salt of ammonia or amines to nitriles;
iii) transformation of nitriles into imido esters followed by the
condensation with NH3 or amines (Pinner synthesis).1,3 In several
cases, the preparation needs high temperatures,4 strongly reducing
agents,5 highly acidic or alkaline conditions.6
aDipartimento di Scienze Chimiche, Universita` di Padova, Via Marzolo 1,
35131, Padova, Italy. E-mail: diego.montagner@unipd.it; Fax: +39-049-
8275161; Tel: +39-049-8275172
bDipartimento di Scienze Chimiche e Farmaceutiche, Universita` di Trieste,
Via Giorgieri 1, 34127, Trieste, Italy
cDipartimento di Scienze Ambientali, Universita` Ca’ Foscari di Venezia,
Dorsoduro 2137, 30123, Venezia, Italy
† Electronic supplementary information (ESI) available. CCDC reference
numbers 811783–811786. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c1dt10638d
8664 | Dalton Trans., 2011, 40, 8664–8674
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Chart 1 Synthetic procedures for the amidine Platinum(II) complexes (L = PPh3, PMePh2).
NH C(R){nucleobase(-H)}, respectively] (Chart 2), have been
obtained in the amino form, namely NH2-C(Ph){1-MeCy(-2H)}
and NH2-C(Ph){9-MeAd(-2H)}, and this isomer is the preferred
one, as confirmed by the structural characterization in the solid
state and in solution. The stabilization of the imino tautomer
through metal coordination has been also investigated by reacting
these amidines with the complex cis-L2Pt(ONO2)2 (L = PPh3) con-
taining the labile nitrato ligands.12 The adducts, tentatively formu-
lated as cis-[L2PtNH C(Ph){nucleobase(-H)}](NO3)2, quantita-
tively convert into cis-[L2PtNH C(Ph){nucleobase(-2H)}]NO3,
by addition of a “proton sponge”.
The single crystal X-ray analysis of the cytosine derivative cis-
[(PPh3)2PtNH C(Ph){1-MeCy(-2H)}]NO3 confirms the coordi-
nation features of the anionic ligand previously described for the
PMePh2 analogue10 and allows the examination of the structural
differences between the free and the coordinated benzimidamides.
Finally, the reactivity of Me3C–CN and Ph2(H)C–CN has been
explored, showing that the insertion of these hindered nitriles
into the platinum–nucleobase bond is incomplete in the case of 9-
MeAd, while the amidine complexes cis-[(PPh3)2PtNH C(R){1-
MeCy(-2H)}]NO3 [R = Me3C and Ph2(H)C] can been isolated
in high yield. They are structurally analogous to the acetonitrile
and benzonitrile derivatives, suggesting that the use of appropriate
nitriles can lead to a variety of metallacycle complexes from which
new amidines can be prepared.
Chart 2 Synthetic pathway for the synthesis of amidines and their
coordination properties.
Experimental section
metal as cis-(PPh3)2PtCl2, as shown in Chart 2 for the 1-MeCy
derivative.
Instrumentation and materials
The nitrato salt of N-(1-methyl-2-oxo-1,2-dihydropyrimidin-
4-yl)benzimidamide, [NH2 C(Ph){1-MeCy(-H)}]NO3, has been
characterized by single crystal X-ray analysis and in solution
by NMR at variable temperature. In the solid state, strong
intermolecular H-bonds stabilize a dimeric structure of the cation,
which is also maintained in solution of DMSO-d6 or DMF-d7.
The neutral species, of which the amino and the imino tau-
tomeric forms are expected [NH2-C(R){nucleobase(-2H)} and
1H, 13C and 31P NMR experiments were recorded on a Bruker
AVANCE 300 MHz operating at 300.13, 121.49 and 100.61 MHZ,
respectively. 15N NMR with Bruker 400 AMX-WB spectrometer
(operating at 40.6 MHz). The H and 13C chemical shifts were
1
referenced to the residual impurity of the solvent and to TMS. The
external references were H3PO4 (85% w/w in D2O) for 31P and
CH3NO2 (in CDCl3 at 50% w/w) for 15N. Inverse detected spectra
were obtained through heteronuclear multiple bond correlation
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1
(HMBC) experiments, using parameters similar to those previ-
ously reported.13
IR spectra were recorded on a JASCO FT/IR-4100 type
A Fourier Transform Infrared Spectrometer using Nujol mulls
between KBr discs.
N 23.85. H NMR in D2O (d, ppm): 8.13 (d, 3JHH = 7.1 Hz, 1H,
3
H6); 7.81–7.59 (c.m., 5H, Ph); 6.50 (d, JHH = 7.1 Hz, 1H, H5);
3.53 (s, 3 H, N(1)CH3). 13C{ H} NMR in D2O (d, ppm): 166.8
1
(CCN); 158.3 (C2); 153.8 (C8); 135.0 (Cp); 130.2 (Cm); 129.3 (Co);
1
128.1 (Ci); 99.2 (C5); 39.1 (NCH3). H NMR in DMSO-d6 (d,
All the solvents (CH2Cl2, MeOH, PhCN, CDCl3, D2O,
DMSO-d6, DMF-d7), HCl, NaOH, Ph2C(H)CN, (CH3)3CCN
and CH(OC2H5)3 are Aldrich products. 9-MeAd,14 1-MeCy,15 cis-
[(PPh3)2Pt(m-OH)]2(NO3)2,9 cis-[(PPh3)2PtNH C(R){1-MeCy
(-2H)}]NO3 (R = Me, 1a; Ph, 1b) and cis-[(PPh3)2PtNH C(Ph){9-
MeAd(-2H)}]NO3 (R = Me, 2a; Ph, 2b) were synthesized as
previously reported.9,10
ppm): 12.12 (br s, 1H, NH); 11.87 (br s, 1H, NH); 9.81 (br s,
1H, NH); 8.26 (d, JHH = 7.5 Hz, 1H, H6); 7.97–7.88 (c.m., 5H,
3
Ph); 6.48 (d, 3JHH = 7.5 Hz, 1H, H5); 3.44 (s, 3 H, N(1)CH3). IR:
nNH = 3458 and 3229 cm-1; nCO = 1651 cm-1. Suitable crystals for
X-ray analysis were obtained from slow diffusion of Et2O vapors
into a MeOH solution of 3b, at r.t. With the same procedure, 3a
was obtained starting from cis-[(PPh3)2PtHN C(Me){1-MeCy
(-2H)}]NO3. (yield 75%). Elemental analysis calcd (%) for 3a;
C7H11N5O4: C 36.68, H 4.85, N 30.54; found C 36.40, H 4.70, N
Synthetic work
1
3
30.85. H NMR in D2O (d, ppm): 8.13 (d, JHH = 7.05 Hz, 1H,
H6); 6.40 (d, 3JHH = 7.05 Hz, 1H, H5); 3.57 (s, 3 H, N(1)CH3); 2.48
(s, 3 H, CCH3). 1H NMR in DMSO-d6 (d, ppm): 11.22 (br s, 1H,
1. cis-[(PPh3)2PtHN C(CMe3){1-MeCy(-2H)}]NO3, 1c.
A
suspension of cis-[(PPh3)2Pt(m-OH)]2(NO3)2 (32 mg, 2.0 ¥ 10-2
mmol) and 1-MeCy (5.2 mg, 4.0 ¥ 10-2 mmol) in (CH3)3CCN
(2 mL) and CH2Cl2 (4 mL) was stirred at r.t. for 24 h. Addition
of Et2O to the resulting yellow solution afforded the precipitation
of a pale yellow solid, which was recovered by filtration, washed
several times with Et2O, and dried under vacuum. The yield of
1c was 32 mg, 80%. Elemental analysis calcd (%) for C46H45N5O4
P2Pt·1/2CH2Cl2: C 54.15, H 4.50, N 6.79; found C 54.62, H 4.66,
N 7.02. 1H NMR in CDCl3 (d, ppm): 7.50–7.21 (c.m., 30 H, Ph);
NH); 11.12 (br s, 1H, NH); 11.08 (br s, 1H, NH); 8.24 (d, 3JHH
=
6.51 Hz, 1H, H6); 6.22 (d, 3JHH = 6.51 Hz, 1H, H5); 3.51 (s, 3H,
N(1)CH3); 2.42 (s, 3H, CCH3).
4. [NH2 C(Ph){9-MeAd(-H)}]NO3, 4b. With an analogue
procedure, starting from 2b (136 mg, 1.3 ¥ 10-1 mmol), 4b was
prepared (55 mg, yield 89%). Elemental analysis calcd (%) for 4b;
C13H13N7O3 : C 49.53, H 4.16, N 31.08; found C 49.32, H 4.34, N
31.25. 1H NMR in D2O (d, ppm): 8.79 (s, 1H, H2); 8.36 (s, 1H, H8);
3
5
7.12 (d, JHH = 7.2 Hz, 1 H, H6); 6.03 (dd, 3JHH = 7.1 Hz, JHP
=
1.5 Hz, 1 H, H5); 5.89 (br s, 1H, NH); 2.65 (s, 3 H, N(1)CH3);
1
7.91–7.64 (c.m., 5H, Ph); 3.39 (s, 3H, N(9)CH3). 13C{ H} NMR
1
0.86 (s, 9H, CMe3). 31P{ H} NMR in DMSO-d6 (d, ppm): 8.29
(1JPPt = 3436 Hz); 8.01 (1JPPt = 3479 Hz), 2JPP = 24.9 Hz. 1H NMR
in D2O (d, ppm): 162.7 (CCN); 159.7 (C2); 153.3 (C6); 151.3 (C4);
in DMSO-d6 (d, ppm): 7.79–7.30 (c.m., 30 H, Ph); 7.27 (d, 3JHH
=
147.9 (C8); 135.4 (C5); 132.5 (Cp); 130.2 (Cm); 129.1 (Co); 128.9
1
7.4 Hz, 1H, H6); 5.92 (dd, 3JHH = 7.4 Hz, 5JHP = 1.0 Hz 1H, H5);
(Ci); 99.2 (C5); 30.9 (NCH3). H NMR in DMSO-d6 (d, ppm):
11.68 (br s, 1H, NH); 10.96 (br s, 2H, NH); 8.87 (s, 1H, H2); 8.68
(s, 1 H, H8); 7.91–7.77 (c.m., 5H, Ph); 3.90 (s, 3 H, N(9)CH3).
IR: nNH = 3453 and 3223 cm-1. With the same procedure, 4a
was obtained starting from cis-[(PPh3)2PtHN C(Me){9-MeAd
(-2H)}]NO3. (yield 79%). Elemental analysis calcd (%) for 4a;
C8H11N7O3: C 37.95, H 4.39, N 38.71; found C 38.20, H 4.45, N
5.84 (br s, 1H, NH); 3.35 (s, 3 H, N(1)CH3: 0.78 (s, 9H, CMe3).
2. cis-[(PPh3)2PtHN C(CHPh2){1-MeCy(-2H)}]NO3, 1d.
A suspension of cis-[(PPh3)2Pt(m-OH)]2(NO3)2 (502 mg, 3.1 ¥ 10-1
mmol), 1-MeCy (79.2 mg, 6.3 ¥ 10-1 mmol) and Ph2C(H)CN
(128 mg, 6.6 ¥ 10-1 mmol) in CH2Cl2 (5.0 mL) was stirred at
◦
1
ca 25 C for 3 days. A trace amount of solid was eliminated by
38.42. H NMR in D2O (d, ppm): 8.77 (s, 1H, H2); 8.39 (s, 1H,
1
filtration and Et2O (20 mL) was then added to the resulting yellow
solution. The powdered precipitate was recovered by filtration,
washed several times with Et2O, and dried under vacuum, to
give a yellow solid. The yield of 1d was 585 mg, 92%. Elemental
analysis calcd (%) for C55H47N5O4 P2Pt·CH2Cl2 : C 56.81, H 4.18,
H8); 3.93 (s, 3 H, N(1)CH3); 2.61 (s, 3 H, CCH3). H NMR in
DMSO-d6 (d, ppm): 11.56 (br s, 1H, NH); 10.94 (br s, 1H, NH);
8.70 (br s, 1H, NH); 8.94 (s, 1H, H2); 8.79 (s, 1H, H8); 3.87 (s, 3H,
N(1)CH3); 2.52 (s, 3 H, CCH3).
1
N 5.91; found C 56.49, H 4.21, N 6.09. H NMR in CDCl3 (d,
5. H2N-C(Ph){1-MeCy(-2H)}, 5b. To a solution of 3b
(120 mg, 4.1 ¥ 10-1 mmol) in H2O (4 mL) a solution of NaOH
0.1 M (4.1 mL) was added. The white precipitate that immediately
formed was recovered by filtration, washed several times with H2O
and dried under vacuum. The yield of 5b was 85%. Elemental
analysis calcd (%) for 5b; C12H12N4O: C 63.15, H 5.31, N 24.53;
ppm): 7.62–6.68 (c.m., 41 H, Ph and H6); 6.07 (br s, 1H, NH;
5.93 (dd, 3JHH = 7.1 Hz, 5JHP = 1.2 Hz 1 H, H5); 5.18 (s, 1H, CH);
1
2.68 (s, 3H, N(1)CH3. 31P{ H} NMR in DMSO-d6 (d, ppm): 7.71
(1JPPt = 3523 Hz); 7.27 (1JPPt = 3402 Hz), 2JPP = 25.3 Hz. 1H NMR
in DMSO-d6 (d, ppm): 7.75–6.75 (c.m., 41 H, Ph and H6); 6.28
(br s, 1H, NH); 5.86 (dd, 3JHH = 7.1 Hz, 5JHP = 1.2 Hz 1 H, H5);
5.28 (s, 1H, CH); 3.35 (s, 3H, N(1)CH3).
1
found C 62.96, H 5.05, N 24.38. H NMR in CDCl3 (d, ppm):
3
11.56 (br s, 1H, NH); 7.95–7.44 (c.m., 5H, Ph); 7.42 (d, JHH
=
3. [NH2 C(Ph){1-MeCy(-H)}]NO3, 3b. To a solution of 1b
(215 mg, 2.1 ¥ 10-1 mmol) in CH2Cl2 (10 mL), a solution of HCl
0.05 M (8.53 mL, 4.3 ¥ 10-1 mmol) was slowly added and the
mixture let stirring for 2 h at r.t. The aqueous phase was then
separated through a separating funnel and the solvent evaporated
under vacuum at ambient temperature. The resulting white solid
3b was 54.4 mg (yield 89%). Elemental analysis calcd (%) for 3b;
C12H13N5O4: C 49.48, H 4.51, N 24.03; found C 49.30, H 4.68,
6.9 Hz, 1 H, H6); 7.14 (br s, 1H, NH); 6.25 (d, 3JHH = 6.9 Hz, 1 H,
H5); 3.52 (s, 3 H, N(1)CH3). 13C{ H} NMR in CDCl3 (d, ppm):
1
173.0 (CCN); 165.1 (C4); 157.6 (C2); 146.0 (C6); 135.3 (Cp); 131.0
(Cm); 128.5 (Co); 127.8 (Ci); 105.1 (C5); 38.3 (NCH3). 1H NMR in
DMSO-d6 (d, ppm): 11.11 (br s, 1H, NH); 9.14 (br s, 1H, NH);
8.03–7.57 (c.m., 5H, Ph); 7.87 (d, 3JHH = 7.0 Hz, 1H, H6); 6.06 (d,
3JHH = 7.0 Hz, 1H, H5); 3.32 (s, 3 H, N(1)CH3). IR: nNH = 3444
and 3183 cm-1.
8666 | Dalton Trans., 2011, 40, 8664–8674
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between 1a:1b was 3 : 2 but after 5 days at room temperature only
1b was detectable.
6. H2N-C(Ph){9-MeAd(-2H)}, 6b. To a solution of 4b
(184 mg, 5.8 ¥ 10-1 mmol) in H2O (6 mL) a solution of NaOH 0.1 M
(5.90 mL) was slowly added. The white precipitate immediately
formed was recovered by filtration, washed with H2O and dried
under vacuum. The yield of 6b was 97 mg, 66%. Elemental analysis
calcd (%) for 6b; C13H12N6: C 61.90, H 4.80, N 33.30; found C
62.15, H 4.62, N 33.52. 1H NMR in CDCl3 (d, ppm): 11.10 (br s,
1H, NH); 8.69 (s, 1H, H2); 8.11–7.45 (c.m., 6 H, Ph and H8);
X-ray structure determination
Crystal data and details of data collections and refinements for
the structures reported are summarized in Table 1. Intensity data
of compounds 1b, 3b, and 5b were collected at room temperature
(293(2) K) on a Nonius DIP-1030H system (Mo-Ka radiation, l =
1
5.95 (br s, 1H, NH); 3.89 (s, 3 H, N(9)CH3). 13C{ H} NMR in
˚
0.71073 A), those of 6b on a Nonius FR591 rotating anode (Cu-
CDCl3 (d, ppm): 163.4 (CCN); 160.0 (C2); 152.7 (C6); 151.8 (C4);
˚
Ka, l = 1.54178 A), equipped with Kappa CCD imaging plate. Cell
143.5 (C8); 136.5 (C5); 132.4 (Cp); 129.3 (Cm); 128.7 (Co); 128.4
refinement, indexing and scaling for the data sets were performed
by using Denzo and Scalepack programs.16 All the structures were
solved by direct methods and subsequent Fourier analyses17 and
refined by the full-matrix least-squares method based on F2 with all
observed reflections.17 A molecule of diethylether was detected in
the DF map of 1b. Hydrogen atoms were positioned at geometrical
calculated positions except those of amine group in 3b, 5b, and 6b.
All the calculations were performed using the WinGX System, Ver
1.80.05.18
1
(Ci); 30.6 (NCH3). H NMR in DMSO-d6 (d, ppm): 10.25 (br s,
1H, NH); 8.79 (br s, 1H, NH); 8.63 (s, 1H, H2); 8.28 (s, 1H, H8);
8.13–7.57 (c.m., 5 H, Ph); 3.79 (s, 3H, N(9)CH3). IR: nNH = 3466
and 3252 cm-1.
Suitable crystals for X-ray analyses of 5b and 6b were obtained
from slow evaporation at r.t. of a solution in CDCl3 into a NMR
tube.
7. Relative stability of the amidine complexes. i) 18.5 mg
of cis-[(PPh3)2Pt(m-OH)]2(NO3)2 (1.2 ¥ 10-2 mmol) and 1-MeCy
(3.0 mg, 2.4 ¥ 10-2 mmol) were rapidly dissolved in 0.8 mL of
DMSO-d6 solution containing equimolar amounts of Me3CCN
(39 mg), Ph2C(H)CN (93 mg) and CH3CN (20 mg) in order to
have Pt/each nitrile ratio 1/20. On the base of 31P NMR spectra,
immediately after the dissolution 1a, 1c and 1d were in a ratio of
9 : 0 : 1, after 24 h the corresponding ratio was 7 : 1 : 2 and after
5 days at r.t. it became 2 : 1 : 7. ii) 21.2 mg of cis-[(PPh3)2Pt(m-
OH)]2(NO3)2 (1.3 ¥ 10-2 mmol) and 1-MeCy (3.3 mg, 2.6 ¥ 10-2
mmol) were dissolved in a mixture of 0.3 mL of CH3CN and
0.3 mL of PhCN and the reaction was followed through 31P NMR
with D2O as insert. Immediately after the dissolution the ratio
Crystallographic data for this paper is available in the ESI,
CCDC numbers 811783–811786.†
Results and discussion
Syntheses of the amidine complexes cis-[(PPh3)2PtNH C(R)-
{nucleobase(-2H)}]NO3
We have recently shown that the dinuclear hydroxo complex cis-
[(PPh3)2Pt(m-OH)]2(NO3)2 reacts with 1-MeCy or 9-MeAd, in
CH3CN or PhCN, to give quantitatively the azametallacycles
cis-[(PPh3)2PtNH C(R){nucleobase(-2H)}]NO3, as depicted in
Chart 1. By monitoring the reaction with 31P NMR, it was
Table 1 Crystal data and details of structure refinements for compounds 1b, 3b, 5b, and 6b
1b·OEt2
3b
5b
6b
Empirical formula
Formula weight
Crystal system
Space group
C52H51N5O5P2Pt
1083.01
C12H13N5O4
291.27
Monoclinic
P 21/n
10.426(2)
9.226(2)
C12H12N4O
228.26
Monoclinic
P 21/n
7.374(2)
C13H12N6
252.29
Triclinic
Triclinic
¯
¯
P 1
P1
˚
a (A)
12.795(2)
14.002(2)
14.667(3)
114.857(9)
94.249(10)
95.843(10)
2351.9(7)
2
10.681(2)
10.645(3)
12.011(3)
110.88(2)
91.87(2)
95.54(2)
1266.7(5)
4
˚
b (A)
11.022(3)
13.990(3)
˚
c (A)
14.336(3)
a (◦)
b (◦)
g (◦)
94.01(2)
100.40(2)
3
˚
Volume (A )
Z
1375.6(5)
4
1.406
0.109
608
26.73
16205
2901
0.0391
2134
1118.4(5)
4
1.356
0.092
480
25.02
8953
1874
0.0887
795
161
0.866
0.0521
0.1156
0.207, -0.164
Dc (g cm-3)
1.529
3.105
1092
27.88
34811
10835
0.0550
8219
587
1.323
0.699
528
60.04
9412
3584
0.0515
1458
357
m Mo-Ka, (mm-1)b
F(000)
qmax (◦)
Reflns collected
Unique reflections
Rint
Observed I > 2s(I)
Parameters
Goodness of fit (F2)
R1 (I > 2s(I))a
200
0.949
1.085
0.0621
0.1920
0.412, -0.261
0.961
0.0400
0.0943
0.996, -0.541
0.0507
0.1238
0.132, -0.167
a
wR2
3
˚
Residuals (e/A )
1
2
2
2
2
2
b
a R1 = R ꢀFo|–|Fcꢀ/R|Fo|, wR2 = [R w (Fo 2 – Fc ) /Rw (Fo ) ] m Cu-Ka for 6b.
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Syntheses and characterization of the amidines [NH2 C(R)-
{nucleobase(-H)}]NO3 and NH2-C(R){nucleobase(-2H)}
shown that the formation of cis-[(PPh3)2PtNH C(R){1-MeCy
(-2H)}]NO3 (R = Me, 1a; Ph, 1b) occurs at ambient tempera-
ture and no intermediates are detectable. In contrast, 9-MeAd
undergoes deprotonation, givinginitiallythe chelated-N6,N7 aden-
inate complex cis-[(PPh3)2Pt{9-MeAd(-H),N6N7}]NO3,19 which
reacts with a solvent molecule only after several hours at room
temperature, affording quantitatively the insertion products cis-
[(PPh3)2PtNH C(R){9-MeAd(-2H)}]NO3, (R = Me, 2a; Ph, 2b).
A similar reaction pattern is observed when the deprotonation
of 1-MeCy occurs in solution of CH2Cl2 in the presence of the sub-
stituted acetonitriles Me3CCN or Ph2C(H)CN and the amidines
cis-[(PPh3)2PtNH C(R){1-MeCy(-2H)}]NO3 [R = Me3C, 1c;
Ph2(H)C, 1d] are formed in quantitative yield (by 31P NMR). The
products 1c and 1d have been isolated as pure compounds and
characterized by multinuclear NMR spectroscopy in CDCl3 and
DMSO-d6. In both the solvents, the compounds exhibit features
similar to those of the CH3CN and PhCN analogous (1a and
1b), as shown in Table T1 (ESI†) where the 31P and selected
1H NMR in CDCl3 data are collected. As previously observed
for 1a, complexes 1c and 1d in solution of DMSO-d6 appear
stable while in chlorinated solvents they slowly (a few days at
25 ◦C) decompose to give the free nitrile and uncharacterized
platinum complexes. The reaction is reversible as indicated by the
immediate and quantitative formation of the amidine complexes
1c and 1d upon addition of an excess of Me3CCN or Ph2C(H)CN,
respectively. The relative thermodynamic stability of the amidinic
complexes 1a–1b was investigated by reacting the hydroxo complex
and 1-MeCy in mixture of CH3CN and PhCN (see experimental).
1a and 1b are rapidly formed in a molar ratio ca. 3 : 2 and the
composition of the reaction mixture slowly changed, leading to
the quantitative presence of 1b in few days at r.t. The effect
of the stabilization due to the presence of phenyl rings in the
nitrile molecule is confirmed in another experiment where it has
been observed that, carrying out the condensation reaction in
DMSO-d6 with an equimolar mixture of CH3CN, Me3CCN and
Ph2C(H)CN, the relative concentration of 1a, 1c and 1d, at the
equilibrium (after 5 days at 25 ◦C) was 2 : 1 : 7.
Addition of two equivalents of aqueous HCl to CH2Cl2 solu-
tions of 1a,b and 2a,b leads to the immediate and quantitative
protonation of the amidine ligands, released as nitrate salts
[NH2 C(R){nucleobase(-H)}]NO3 (nucleobase: 1-MeCy, R =
Me, 3a; Ph, 3b; 9-MeAd, R = Me, 4a; Ph, 4b), and the concomitant
coordination of the chloride ions to the metal centre (Chart 2).
The platinum containing product, cis-(PPh3)2PtCl2, dissolved in
the chlorinated solvent, can be quantitatively separated from the
reaction mixture.
All these organic compounds are insoluble in chlorinated sol-
vents whereas they easily dissolve in H2O, DMSO and DMF. Com-
pounds 3a and 4a, unlike the benzonitrile derivatives 3b and 4b,
slowly decompose in water (a few days, at room temperature)
with formation of CH3CN and of the protonated nucleobases
[1-MeCyH]NO3 and [9-MeAdH]NO3. Therefore, only 3b and 4b
have been further characterized as neutral species, according to
Chart 2.
Aqueous solutions of 3b and 4b, upon addition of stoichiometric
amounts of NaOH, afford white precipitates of the neutral
amidines NH2-C(Ph){1-MeCy(-2H)} (5b) and NH2-C(Ph){9-
MeAd(-2H)} (6b) which have been characterized in solution by
multinuclear NMR spectroscopy and in the solid state by single
crystal X-ray analysis. These neutral species, insoluble in H2O,
dissolve in CDCl3 and DMSO-d6, where they appear indefinitely
1
stable. The H NMR spectra of 5b and 6b exhibit well-resolved
doublets for the cytosine H5 and H6 protons and very sharp
singlets for H2 and H8 adenine signals. The NH resonances
are observed as two broad singlets having the same relative
intensities, with very different chemical shift values (Dd 4.4 and
1
5.1 ppm for 5b and 6b, respectively, in CDCl3). H,15N HMQC
experiments (Fig. S2, ESI†) of 5b indicate that both the NH
signals at d 11.56 and 7.14 ppm correlate with the same 15N
nucleus (at d -266 ppm), in agreement with the presence of
two hydrogen atoms bound to the same nitrogen. Of the two
possible tautomers of these amidines (Chart 2), the amino form
appears to be the only one detectable in solution, as predicted
by Prevorsek.20 The large chemical shift difference for the NH2
protons can be accounted for by the presence of relatively
strong intermolecular hydrogen bonds, as detected in the solid
state structure of 5b and 6b and discussed in the next section
(Fig. S3 and S4, ESI†).
As previously seen for CH3CN and PhCN,9,10 the reaction
of cis-[(PPh3)2Pt(m-OH)]2(NO3)2 with 9-MeAd in CH2Cl2, in
the presence of an excess of Me3CCN or Ph2C(H)CN, rapidly
affords the intermediate cis-[(PPh3)2Pt{9-MeAd(-H),N6N7}]+,19
which slowly reacts with the nitrile to give the amidines
cis-[(PPh3)2PtNH C(R){9-MeAd(-2H)}]NO3 (R = Me3C, 2c;
Ph2(H)C, 2d). However the insertion of the nitrile molecule into
the Pt-N(6) bond is not quantitative, even in the presence of a large
excess of nitrile. As an example, the 31P NMR spectrum of a mix-
ture of cis-[(PPh3)2Pt(m-OH)]2(NO3)2, 9-MeAd and Ph2C(H)CN,
in molar ratio 1 : 2 : 20, is shown in Fig. S1 (ESI†). The AB pattern
detected in the fresh prepared solution (Fig. S1a, ESI†), at d 8.78
1
A more complex H NMR pattern was observed in the case
of the protonated amidine 3b. In fact, whereas in D2O the
endocyclic protons H(6) and H(5) are observed as sharp doublets,
3
with JHH = 7.07 Hz, they occur as poorly resolved doublets in
DMSO-d6. This unprecedented behaviour prompted us to study
the system in DMF-d7 at variable temperature. In this medium,
at 25 ◦C, H5 and H6 show very broad singlets at 7.4 and
9.0 ppm, respectively, and a sharp singlet at 3.57 ppm for the
N(1) methyl group. The NH proton resonances, undetectable in
D2O, are observed as very broad singlets, with the same relative
intensities, at 13.4, 12.9 and 12.6 ppm in DMF-d7. Decreasing the
temperature to -55 ◦C, a sharpening of all the NH resonances
is observed, with the concomitant progressive merging of those
at higher field, to give a single resonance at 13.8 ppm, as shown
in Fig. 1. A similar trend with the temperature is observed for
2
(1JPPt = 3860 Hz) and 6.16 ppm (1JPPt = 3100 Hz; JPP = 20 Hz),
is attributable to the N6,N7-chelated adeninate complex, and its
relative concentration is about 40% after 8 days (Fig. S1b, ESI†).
These results reflect the relatively high thermodynamic stability of
the five membered N6,N7-chelated adenine complex with respect
to the amidine derivative 2d. Although 2c and 2d were not isolated
as pure compounds, their 31P NMR in CDCl3 parameters are
included in Table T1 (ESI†). The chemical shift and coupling
constant values for these compounds also suggest a structure
similar to those of 2a and 2b, previously characterized.9,10
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Fig. 1 Temperature dependence of the equilibrium between the monomer 3b and the dimer 3b¢ in DMF-d7. Only selected temperatures are shown.
the H5 and H6 signals, which become sharp doublets at low
temperature.
two different H-bond interactions: of the aminic proton with the
nitrate anion, and of only one iminium proton with carbonylic
oxygen. This may be a situation dictated by packing requirements
of the crystalline state.
The presence of the three major resonances in the H-bond
region may be accounted for due to the dimeric structure of 3b¢.
Alternatively, the equilibrium, fast at room temperature, between
the dimeric strucure 3b¢¢ and 3b¢¢¢ can be proposed. However, this
situation would lead to an averaged NH resonance in a more
shielded region. Thus the arrangement 3b¢ that is to be preferred,
would require the slow proton exchange between water (always
present) and the aminium an iminium centers, and also the low
rotation around the CN double bond.
NMR investigation of the H-bonded monomer–dimer equilibrium
of 3b
Inspection of Fig. 5 reveals in 3b the presence of dimeric species
formed via H-bonding between the iminium protons at N2 and
the carbonylic oxygen O2. In addition, the aminic proton N4 and
one nitrate oxygen are at H-bonding distance. These features are
almost exactly reproduced in solution of DMF-d7, as revealed
by the 1H NMR spectra monitored at different temperatures
(Fig. 1). The dynamic behaviour in solution discloses other
relevant features.
At higher temperatures, the increasing exchange rates for the
monomer–dimer equilibrium bring about the broadening and the
final collapse of the NH resonances present in equivalent positions.
This dynamic behaviour can be monitored and quantified in terms
In the H NMR spectrum recorded at -50 ◦C, three major
1
broad peaks are observed between 12.2 and 13.2 ppm, i.e. within
the typical H-bonding resonance range, beside three minor peaks:
one in the H-bonding resonance range (d = 13.8 ppm), the last
two are somehow more shielded (d = 10.75 and 10.42 ppm). These
are NH resonances which can be accounted for due to the dimer–
monomer equilibrium illustrated in Chart 3.
On the basis of this scheme, two major resonances, in the H-
bond region and assigned to the NH protons of the iminium
moiety, account for the formation of the dimer 3b¢. The minor
resonances in the more shielded region are again the NH
resonances of the iminium moiety in the “free” monomer 3b,
and the last major and minor resonances in the H-bond region
pertain to the aminic proton of the dimer and of the monomer,
respectively, that are H-bonded to the nitrate anion. The presence
of H-bonds in solution between aminic protons and inorganic
anions is documented.21 This case is somehow different from
the picture given by the X-ray diffraction analysis reported in
Fig. 5, which highlights the presence of a dimer 3b¢¢ with only
◦
of equilibrium constants (see below) up to about 0 C; at higher
temperatures contaminations by other phenomena (rotations and
proton exchanges) will interfere.
The thermodynamic behaviour can be monitored from other
resonances of the monomer-dimer system, which therefore must
be exactly attributed. Proton 5 and 6 of the 2-oxopyrimidine ring
are in the form of doublets, in both structures, and therefore easily
recognized, but not singularly assigned. The attribution procedure
occurs via a NOESY experiment that at -55 ◦C is ambiguous: both
the monomer and the dimer are in the “negative” NOE region,
and the dipolar interactions are indistinguishable from exchange
interactions. At 20 ◦C the resonances of the 2-oxopyrimidine ring
collapse into two broad singlets. In the NOESY spectrum in Fig.
S5 (ESI†), the deshielded singlet at 8.60 ppm belonging to proton
6 gives dipolar interaction with the methyl signal at 3.75 ppm. The
shielded singlet at 7.02 ppm gives a dipolar interaction with the
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Chart 3 Dimer–monomer equilibrium of 3b.
intense water signal at 3.95 ppm, denouncing the proximity to the
aminic proton (which exchanges fast with water protons): this is
the signal of proton 5 (See Fig. S5, ESI†).
At low temperatures, the resonances of protons 5 and 6 split
into two pairs of doublets. The doublets of protons 6 resonate in a
free region and will be utilized for a quantitative evaluation of the
thermodynamics via the van’Hoff analysis of the monomer–dimer
interconversion.
temperature. The equilibrium constant K for the process is defined
by:
⎯K⎯md⎯→
←⎯⎯⎯
Kdm
′
dimer 3b
2 monomer 3b
′
[dimer 3b ]
where
and 2 [dimer 3b¢] + [monomer 3b] =
K =
[monomer 3b] 2
0.011 mol L-1
This is a non-equimolar equilibrium, and therefore the con-
centration of 3b in DMF-d7 must be determined with utmost
accuracy, more for a correct evaluation of the equilibrium entropy
DS◦ than for the evaluation of the equilibrium enthalpy DH◦. The
monomer 3b and DMF-d7 were weighed in the NMR tube, and
the concentration was checked after the measurement session by
the further addition of a weighed amount of a substance with
relevant molecular weight and one small 1H peak resonating in a
free region: the choice was triethyl orthoformate.
Van’t Hoff plot
The integration of NMR peaks is, among the NMR parameters,
the one measured with the least accuracy, also because of the limits
of the instrumental numeric procedure. We therefore adopted
the strategy of fitting the peaks into a combination of Gaussian
and Lorentzian functions, followed by the analytical integration
of these. The fitting is computationally accomplished with the
Levenberg–Marquardt method.22 Accurate integration values can
be acquired between -55 and 15 ◦C, i.e. just below the coalescence
From the Van’t Hoff plot, the thermodynamic parameters
DH◦ = -1.58 kcal L mol-1 and DS◦ = 9.01 cal K-1 L mol-1 are
determined.
8670 | Dalton Trans., 2011, 40, 8664–8674
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˚
The positive entropy change for a dimerization process is
unexpected so we then verified the accuracy of the results
with the analytical integration of other signals, the NH and
the methyl resonances, retrieving very similar positive values.
Some comments on this point are necessary. Positive entropy
changes for dimerization processes promoted by intermolecular
H-bonding are not common, and are invariably associated with
tetrahedral distortion in 1b, with deviations up to 0.22 A from
their mean plane. The amidine fragment results bowed with the
cytosine and phenyl from the benzonitrile that formed an angle
of 15.0(1)◦, while the nucleobase ring forms a dihedral angle
of 49.2(1)◦ with the mean coordination plane N2P2. Inside the
six-membered ring fragment, the geometrical parameters indicate
an electron delocalization. The molecule shows a p–p stacking
between the cytosine and PPh3 phenyl ring C(19) and a slightly
stronger interaction between the phenyl rings C(25) and C(31) of
condensed phase experiments run in highly polar solvents.23
A
rationalization has been offered.24 Since the molecular dipole
vectors of two molecules such as 3b mutually cancel upon the
formation of a H-bonded dimer, the latter species possesses no
molecular dipole vector. Highly polar solvent molecules are heavily
organized around the monomer with relevant dipole vector, but
to a relevantly minor extent around a dimer lacking a molecular
dipole vector.
˚
the two PPh3 (distance between ring centroids of 3.69 and 3.47 A,
dihedral angle 20.34 and 8.38◦, respectively).
The molecular structures of the protonated and neutral benzimi-
damide [NH2 C(Ph){1-MeCy(-H)}]NO3 (3b) and NH2-C(Ph){1-
MeCy(-2H)} (5b) are depicted in Figs. 3 and 4 respectively. The
X-ray structural studies
The X-ray structural determination of complex 1b shows the
insertion of the benzonitrile molecule into the cytosine Pt-N(4)
bond with formation of a six-membered ring, as depicted in Fig. 2.
Selected bond distances and angles are collected in Table 2.
Fig. 3 ORTEP drawing (35% probability ellipsoids) of compound 3b.
Fig. 2 ORTEP drawing (35% probability ellipsoids) of the cation of 1b.
The platinum is bound to the nucleobase donor site N3, the
inserted benzonitrile nitrogen N2, and completes the square planar
coordination through phosphorus donors. The Pt–N3 and Pt–N2
˚
bond distances are of 2.074(4) and 2.052(4) A. The former bond
length appears slightly shorter, the other longer with respect to
the values measured in complexes cis-[(PMePh2)2PtNH C(R){1-
9
MeCy(-2H)}]+ with R = Me (2.097(4) and 2.036(4) A, respec-
˚
10
˚
tively) and Ph (2.112(7) and 2.043(6) A). The Pt–P bond distances
˚
are 2.2955(12) and 2.2898(13) A. The N2P2 donors show a slight
◦
˚
Table 2 Selected bond lengths (A) and angles ( ) of 1b
Pt–N(2)
Pt–N(3)
2.052(4)
2.074(4)
Pt–P(1)
Pt–P(2)
2.2955(12)
2.2898(13)
N(2)–Pt–N(3)
N(2)–Pt–P(1)
N(2)–Pt–P(2)
82.20(14)
165.21(12)
88.48(11)
N(3)–Pt–P(1)
N(3)–Pt–P(2)
P(2)–Pt–P(1)
92.35(10)
166.67(11)
98.92(5)
Fig. 4 ORTEP drawing (35% probability ellipsoids) of compound 5b.
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Table 3 Comparison of bond lengths (A) and angles (◦) of the
˚
amidine fragment in complexes cis-[(PMePh2)2PtNH C(Me){1-MeCy
(-2H)}]NO3 (5a in ref [9]), cis-[(PMePh2)2PtNH C(Ph){1-MeCy(-
2H)}]NO3 (2 ref [10]), 1b and in the free ligands 3b and 5b
5a ref [9] 2 ref [10] 1b
3b
5b
N(3)–C(4)
C(4)–N(4)
N(4)–C(3)
C(3)–N(2)
1.358(7) 1.339(10) 1.347(6) 1.306(3)
1.356(7) 1.342(10) 1.351(6) 1.399(3)
1.337(7) 1.302(10) 1.342(6) 1.361(3)
1.295(7) 1.327(10) 1.312(6) 1.291(3)
1.503(8) 1.488(10) 1.507(6) 1.472(3)
1.329(4)
1.372(4)
1.316(4)
1.325(4)
1.482(4)
C(3)–C(7)
C(3)–N(4)–C(4) 122.6(5) 122.8(8)
N(3)–C(4)–N(4) 125.6(5) 127.5(9)
N(4)–C(3)–N(2) 126.7(5) 126.7(8)
121.1(4) 127.54(17) 122.8(3)
124.9(5) 119.14(17) 122.8(3)
126.6(4) 121.46(19) 125.5(3)
geometrical parameters of the amidine moiety for these species
are reported in Table 3 together with the corresponding values
measured in complexes 1b and cis-[(PMePh2)2PtNH C(R){1-
MeCy(-2H)}]+ (R = Me9 and Ph10). The protonated amidine
3b shows the most striking differences: in particular in the
fragment N(2)–C(3)–N(4)–C(4) where the former bond distance
Fig. 6 ORTEP drawing (35% probability ellipsoids) of the two indepen-
dent molecules of 6b.
polymeric arrangement being alternatively connected along axis
b by H bonds involving the amino group N2 and the endocyclic
nitrogen N7 of the adjacent adenine moiety (N ◊ ◊ ◊ N distance of
˚
is shorter (1.291(3) A) and the other longer (1.361(3), 1.399(3)
˚
A, respectively) with regard to the values found in the metal
˚
ca. 2.97 A), as depicted in Fig. S3 (ESI†). In Table T2 (ESI†)
complexes and in 5b. Correspondingly, the angle C(3)–N(4)–C(4)
of 127.54(17)◦ is the largest among those reported for the presence
of the proton on N(4) which acts as a H donor towards the nitrate.
In addition, the bond angles N(3)–C(4)–N(4) appear narrower
(119.14(17) and 122.8(3)◦ in 3b and 5b, respectively, than the
values observed in the complexes. The phenyl ring is tilted by
29.86(5) and 7.1(2)◦ in amidine molecules 3b and 5b, respectively.
A more interesting observation is that the dihedral angle formed
by the cytosine ring with the C7/C3/N2/N4 moiety, of ca. 9◦ in
both, while upon coordination the measured value observed in 1b
is 25.7(1)◦. In the crystal the molecular cations of 3b are paired
through H-bond interactions, beside the N4–H ◊ ◊ ◊ O2 interaction
cited above (Fig. 5)
we report a comparison of the geometrical parameters of the two
molecules A and B with the data obtained from the Pt complex 2b
and of complexes containing the amidine ligand derived from the
acetonitrile.
These data clearly show a shortening of the C(3)–N(2) bond dis-
˚
tance upon coordination (range 1.279(11)–1.295(8) A vs. 1.324(5)
˚
and 1.334(4) A in the free amidines), with a concurrent widening
of the N(1)–C(6)–N(6) angle (mean values of 127.4◦ vs. 123.3◦,
respectively). Moreover the C(6)–N(6) bond distances in the free
molecules A and B appear elongated with respect to the value
measured upon coordination.
Here, and in the corresponding analysis of the amidine ligand
built from the cystosine base (Table 3), it is not straightforward to
derive a clear trend between the free and the coordinated species.
Making allowance for e.s.d.’s of the geometrical data, this may be
ascribed to the electron delocalization in the molecules, to the H-
bonding scheme observed among the free benzimidamides in the
solid state, but also to the deformations assumed by the chelating
amidine–nucleobase fragment in the complex (likely to accomplish
steric requirements) with respect to the planar arrangement found
in the free molecules.
Coordination properties of the neutral amidines NH2-C(Ph)-
{nucleobase(-2H)}
The data so far reported for the neutral amidines 5b and 6b
clearly support the presence in the solid and in solution of the
amino tautomer (Chart 2). The stabilization of the imino form
likely occurs when these molecules react with the complex cis-
(PPh3)2Pt(ONO2)2.12 In fact, addition of stoichiometric amounts
of 5b or 6b to a colourless solution of the nitrato complex causes
the immediate appearance of a pale yellow colour attributable
to the replacement of the nitrato ligands in the coordination
sphere of the metal and the concomitant formation of the adducts
cis-[(PPh3)2PtNH C(Ph){nucleobase(-H)}]2+, depicted in Chart
2 for the NH C(Ph){1-MeCy(-H)} derivative. Thus, the reaction
of 5b with cis-(PPh3)2Pt(ONO2)2, in CDCl3, causes the immediate
Fig. 5 Crystal packing of 3b showing the dimers formed through H-bond
interactions, (primed atoms at 2-x, 1-y, 1-z).
The structural analysis of 6b shows the presence in the unit
cell of two independent molecules (Fig. 6) which are very similar
as far as their geometry is concerned. These molecules form a
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change of the 31P NMR spectrum, shown in Fig. 7, in which
the singlet at d 3.50 (1JPPt = 4018 Hz) of the nitrato complex
is completely replaced by an AB multiplet at 4.80 (1JPPt = 3504
affinity of the chloride ions toward the Pt(II) centre, with formation
of cis-(PPh3)2PtCl2, allows the quantitative recovery of the metal.
The planar structure of 3b in the solid state is stabilized by a strong
2
-
Hz) and 6.58 ppm (1JPPt = 3543; JPP = 25.1 Hz), attributable
H-bond between the NO3 ion and the hydrogen atom on N(4)
to the adduct cis-[(PPh3)2PtNH C(Ph){1-MeCy(-H)}]2+ (7b).
The values of coupling constants 31P–195Pt, slightly increased (an
average of 72 Hz) with respect to those of the strictly related
species cis-[(PPh3)2PtNH C(Ph){1-MeCy(-2H)}]+ (1b), strongly
support the presence in 7 of the neutral amidine acting as a N,N-
chelating ligand.
cytosine, whereas intermolecular H-bonds between the oxygen of
the cytosine ring and one of the H atoms of the amidine-NH2
group lead to the dimerization of the molecule. The analysis of
the proton spectrum of 3b in DMF-d7 shows the presence of an
equilibrium between the monomer and the dimer, both exchanging
with trace amounts of water, at room temperature.
In addition to MeCN and PhCN, the nucleophylic attack of
the NH2-deprotonated nucleobase occurs to the metal-activated
nitriles Me3CCN and Ph2C(H)CN to give the amidine com-
plexes cis-[(PPh3)2PtNH C(R){nucleobase(-2H)}]NO3, isolated
in high yield for the 1-methylcytosine derivative. The method
of synthesis here reported for the benzimidamides 5a and 6b
can therefore be applied for the preparation of new amidines
of type RC( NH)NHR where the NHR fragment is the model
nucleobase 1-methylcytosine or 9-methyladenine,
Acknowledgements
Dr D. Montagner thanks the University of Padua for the postdoc
fellowship.
Fig. 7 31P{ H}NMR spectra in CDCl3 of: a) cis-(PPh3)2Pt(ONO2)2; b)
1
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Conclusions
The synthesis and structural characterization of the sub-
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