Organometallic phthalazin-1(2H)-ones: Electrochemistry and advantage of solvothermal synthesis

Article abstract of DOI:10.1016/j.poly.2019.04.048

o-Ferrocenylcarbonylbenzoic acid (η⁵-C₅H₅)Fe(η⁵-C₅H₄C(O)C₆H₄COOH)(I)and o-cymantrenylcarbonylbenzoic acid (II)were obtained from ferrocene or (η⁵-C₅H₅)Mn(CO)₃, respectively, by the Friedel–Crafts reaction with phthalic anhydride. Methyl o-ferrocenylcarbonylbenzoate (η⁵-C₅H₅)Fe(η⁵-C₅H₄C(O)C₆H₄COOMe (III)and methyl o-cymantrenylcarbonylbenzoate (CO)₃Mn(η⁵-C₅H₄C(O)C₆H₄COOMe)(IV)were synthesized from I and II, respectively using dimethyl carbonate (DMC)in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)to promote the methylation reaction. 4-Ferrocenylphthalazin-1(2H)-one (V)and 4-cymantrenylphthalazin-1(2H)-one (VI)were obtained by the interaction of hydrazine hydrate with I and II, respectively, by the prolonged reflux or convenient solvothermal synthesis. Cyclic voltammetry measurements showed that compounds III and V undergo reversible one-electron oxidation, localized presumably at the ferrocene unit. For III the irreversible one-electron oxidation is apparently associated with the oxidation of the benzoate fragment. All new compounds were characterized by spectroscopic methods and the molecular structures of II and III were determined by X-ray diffraction analysis.

Full text of DOI:10.1016/j.poly.2019.04.048

Accepted Manuscript
Organometallic phthalazin-1(2h)-ones: electrochemistry and advantage of sol-
vothermal synthesis
S.S. Shapovalov, O.G. Tikhonova, A.V. Kolos, I.V. Skabitsky, S.G. Sakharov,
V.A.Grinberg
PII:
S0277-5387(19)30295-5
https://doi.org/10.1016/j.poly.2019.04.048
POLY 13908
DOI:
Reference:
Polyhedron
To appear in:
Received Date:
Accepted Date:
19 March 2019
25 April 2019
Please cite this article as: S.S. Shapovalov, O.G. Tikhonova, A.V. Kolos, I.V. Skabitsky, S.G. Sakharov,
V.A.Grinberg, Organometallic phthalazin-1(2h)-ones: electrochemistry and advantage of solvothermal synthesis,
Polyhedron (2019), doi: https://doi.org/10.1016/j.poly.2019.04.048
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ORGANOMETALLIC PHTHALAZIN-1(2H)-ONES: ELECTROCHEMISTRY AND
ADVANTAGE OF SOLVOTHERMAL SYNTHESIS
S.S. Shapovalov1, O.G. Tikhonova1, A.V. Kolos 1, I.V. Skabitsky1, S.G. Sakharov1,
V.A.Grinberg2
1.Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences,
Leninskii pr. 31, Moscow, 119991, Russia
2. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences,
Leninskii pr. 31, Moscow, 119991, Russia
Keywords
organometallic complex; ferrocene; phthalazin-1(2H)-one; azaheterocycle; solvothermal
synthesis
Abstract
o-Ferrocenylcarbonylbenzoic acid (η5-C5H5)Fe(η5-C5H4C(O)C6H4COOH) (I) and o-
cymantrenylcarbonylbenzoic acid (II) were obtained from ferrocene or (η5-C5H5)Mn(CO)3,
respectively, by the Friedel-Crafts reaction with phthalic anhydride. Methyl o-
ferrocenylcarbonylbenzoate (η5-C5H5)Fe(η5-C5H4C(O)C6H4COOMe (III) and methyl o-
cymantrenylcarbonylbenzoate (CO)3Mn(η5-C5H4C(O)C6H4COOMe) (IV) were synthesized from I
and II, respectively using dimethyl carbonate (DMC) in the presence of 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) to promote the methylation reaction. 4-
Ferrocenylphthalazin-1(2Н)-one (V) and 4-cymantrenylphthalazin-1(2H)-one (VI) were obtained
by the interaction of hydrazine hydrate with I and II, respectively, by the prolonged reflux or
convenient solvothermal synthesis. Cyclic voltammetry measurements showed that compounds III
and V undergo reversible one-electron oxidation, localized presumably at the ferrocene unit. For III
the irreversible one-electron oxidation is apparently associated with the oxidation of the benzoate
fragment. All new compounds were characterized by spectroscopic methods and the molecular
structures of II and III were determined by X-ray diffraction analysis.
1. Introduction
In recent years, the oxygen atom substitution in carboxylate ligands of transition metal
complexes draw active interest for the preparation of new structures. Reactions of trinuclear
palladium (II) acetate with the formamidinate, triazine, and benzamidine ligands, produce
mononuclear or binuclear compounds depending on the reaction conditions or the isolation
procedure [[1]]. The O=C-NH fragment of heterocyclic compounds can be considered as an
isolobal analogue of carboxylate and was used for complex formation with transition metals.
Phthalazin-1(2H)-one is a heterocyclic compound consisting of the benzene ring fused to the 1,2-
diazine ring with two adjacent nitrogen atoms. It exhibits a tautomeric equilibrium between the

lactime and the lactam forms with the latter, which is predominant due to its minor aromaticity
[[2]]. A variety of pharmacological effects, such as anticancer («Olaparib» is the type of targeted
cancer drug), antidiabetic («Zopolrestat») (Fig. 1), antiasthmatic, antihistaminic,
antihypertensive, antithrombotic, anti-inflammatory, analgesic, antidepressant or antimicrobial
activities, are known for phthalazinones [[3]].
Fig. 1.
The coupling reactions of phthalazin-1(2H)-one with iodoferrocene are directed to the
sterically more accessible lactam nitrogen atom, allowing the selected isolation of N-ferrocenyl
derivatives [[4]]. Ferrocene was the first organometallic compound for which the
antiproliferative properties were reported [[5], [6]]. The sodium salt of o-
carboxybenzoylferrocene named as ferrocerone was patented by Nesmeyanov in 1971 [[7]] and
it is now used to treat iron deficiency anemia. Nowadays, it is the single organometallic
compound used as a drug. The organometallic drug "ferroquine", 7-chloro-4-[[[2-[(N,N-
dimethylamino)methyl]-N-ferrocenyl]methyl]amino]quinoline), an analogue of the standard
antimalarial drug “chloroquine” is currently undergoing clinical trial [[8]]. Ferroquine is active
not only against the chloroquine-sensitive pathogenic plasmodium, but also against the
chloroquine-resistant strains, such as Plasmodium falciparum causing malaria in humans. The
specific cytotoxic properties of ferrocene compounds are also under active studies [[9], [10],
[11]]. In this work we report the preparation of the organometallic phthalazinone ligands with
the ferrocenyl and cymantrenyl fragments.
2.1. Materials
All reactions excluding autoclave synthesis were performed under dry argon using standard
Schlenk technique. Solvents were purified, dried and distilled in an argon atmosphere. All
chemicals and solvents were obtained from commercial sources and used without purification.
Infrared spectra were recorded with a FTIR spectrometer «Bruker Alpha» with Platinum ATR.
1
Elemental analyses were performed on a CHNS analyzer ЕА3000 «EuroVector». H (300.13
MHz) and 13C (75.4 MHz) NMR spectra were recorded on a Bruker “Avance 300” spectrometer,

1
all H and 13C{1H} NMR spectra being referenced to carbons or residual protons present in
deuterated solvents (CDCl3, d6-acetone, d6-dmso) with respect to TMS at δ = 0.
2.2. Synthesis of o-ferrocenylcarbonylbenzoic acid (η5-C5H5)Fe(η5-C5H4C(O)C6H4COOH) (I)
A mixture of phthalic anhydride (5.92 g, 40 mmol) and aluminum chloride (10.67 g, 80 mmol) in
СH2Cl2 (80 ml) was stirred for 15 min at an ice bath. Then the solution of ferrocene (7.44 g, 40
mmol) in СH2Cl2 (80 ml) was added dropwise for 30 min. The mixture colour turned on blue.
Then the mixture was refluxed for 4 h. The resulting mixture was poured into ice mixed with
concentrated HCl (5 ml). After all ice melted, the orange organic layer was separated and the
aqueous layer was extracted with CH2Cl2. To the dark blue water layer in the beaker solution of
Na2S2O4 (4 g in 50 ml of water) was added in small portions till the colour was changed to
yellow. The mixture was transferred to a separatory funnel and extracted with CH2Cl2. The
combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced
pressure. The crude product was purified by column chromatography on silica gel, first using
hexane and then CH2Cl2/EtOAc (1:1, v/v) as eluent. The orange product was precipitated from
CH2Cl2/pentane at -25ºC.
Yield: orange powder, 4.54 g, 34 %.
IR (v, cm-1): 3078 (w), 2828 (sh), 2658 (sh), 2545 (sh), 1732 (w), 1676 (s), 1651 (vs), 1592 (m),
1571 (m), 1487 (w), 1449 (m), 1427 (m), 1375 (m), 1306 (s), 1282 (vs), 1257 (s), 1174 (m),
1147 (m), 1105 (m), 1086 (m), 1051 (m), 1023 (m), 1001 (m), 935 (m), 885 (m), 852 (m), 816
(s), 780 (m), 743 (vs), 707 (vs), 676 (s), 650 (m), 544 (m), 508 (s), 486 (vs), 455 (s), 425 (m).
1H NMR (CDC13, δ, ppm): 4.21 (s, 5H, C5H5) 4.55 (s, 2H C5H4), 4.62 (s, 2H, C5H4), 7.69 – 7.53
(m, 3H, C6H4), 8.04 (d, J = 7,8 Hz, 1H, C6H4)
Elemental analysis for Mr = 334 g/mol
%C %H
Calculated: 64.69 4.22
Found:
64.41 4.85.
2.3. Synthesis of o-cymantrenylcarbonylbenzoic acid (CO)3Mn(η5-C5H4C(O)C6H4COOH) (II).
A mixture of phthalic anhydride (5.92 g, 40 mmol) and aluminium chloride (10.67 g, 80 mmol)
in dichloromethane (80 ml) was stirred for 30 min on an ice bath. Then the solution of
C5H5Mn(CO)3 (8.12 g, 40 mmol) in CH2Cl2 (80 ml) was added dropwise for 30 min and refluxed
for 4 h. The resulting mixture was poured into ice mixed with concentrated HCl (5 ml). After all
ice melted, the pale-yellow precipitate (insoluble in water and CH2Cl2) was separated with
Buchner funnel and purified by recrystallization from boiling isopropyl alcohol.

Yield: yellow crystal, 6.78 g, 51 %
IR (v, cm-1): 2837 (w.), 2560 (w.), 2019 (s.), 1926 (vs.), 1665 (s.), 1593 (m.), 1571 (m.), 1490
(w.), 1459 (m.), 1430 (m.), 1376 (m.), 1305 (s.), 1289 (s.), 1262 (m.) 1180 (w.) 1149 (w), 1088
(w.), 1045 (m.), 1033 (m.), 935 (m.), 861 (m.), 848 (m.), 814 (w.), 776 (m.), 749 (m.), 709 (m.),
662 (s.), 628 (vs.), 580 (w.), 532 (s.), 491 (m.), 419 (w.).
1H NMR (d6-acetone, δ, ppm): 3.79 (s, 1H), 5.10 (s, 2H, C5H5), 5.36 (s, 2H, C5H5), 7.46 (m, H,
C6H4), 7.61-7.85 (m, 2H, C6H4), 8.04-8.15(m, H, C6H4)
Elemental analysis for Mr = 352 g/mol
%C %H
Calculated: 54.57 2.58
Found:
54.74 2.67
2.4
Synthesis
of
methyl
o-ferrocenylcarbonylbenzoate
(η5-C5H5)Fe(η5-
C5H4C(O)C6H4COOMe (III)
DBU (0.30 ml, 1.80 mmol) was added to the dark orange solution of I (0.60 g, 1.80 mmol) in
DMC (10 ml), and the mixture was refluxed for 13 h. The reaction was monitored with TLC
(silica, toluene - ethyl acetate 4 : 1 v/v). Then the solvent was removed under reduced pressure.
The residue produced was extracted by EtOAc (17 ml). The solution obtained was purified with
column chromatography (eluent: EtOAc) to produce the orange solid.
Yield: orange crystals, 0.37 g, 60 %
IR (v, cm-1): 3080 (w.), 2949 (w.), 1718 (s.) 1647 (s.), 1594 (m.), 1571 (m.), 1482 (w.), 1452
(m.), 1439 (m.), 1431 (m.), 1372 (m.), 1344 (w.), 1277 (vs.), 1257 (s.), 1195 (m.), 1166 (m.),
1137 (s.), 1105 (m.), 1085 (s.), 1050 (m.), 1023 (m.), 1002 (m.), 955 (m.), 855 (m.), 821 (s.), 781
(s.), 748 (s.), 711 (s.), 683 (m.), 651 (m.), 503 (s.), 477 (vs.), 451 (s.), 424 (m.).
1H NMR (d6-dmso, δ, ppm): 3.29 (s, HDO), 3.32 (s, H2O), 3.58(s, 3H, Me), 4.25 (s, 5H, C5H5),
4.49 (m, 2H, C5H4), 4.61 (m, 2H, C5H4), 7.63-7.69 (m, 1H, C6H4), 7.74- 7.82 (m, 2H, C6H4),
7.84-7.89 (m, 1H, C6H4).
Elemental analysis for Mr = 348 g/mol
%C %H
Calculated: 65.54 4.63
Found:
65.76 5.20
2.5 Synthesis of methyl o-cymantrenylcarbonylbenzoate (CO)3Mn(η5-C5H4C(O)C6H4COOMe)
(IV)
The synthesis is similar to compound III.

Yield: light yellow powder, 81%
IR (v, cm-1): 3124(w.), 2957(w), 2024(s.), 1939(vs.), 1714(s.), 1665(s.), 1597(w.), 1573(m.),
1461(m) 1434(m.), 1413(w.), 1375(m.), 1290(s.), 1264(m) 1195(m.), 1181(w.), 1135(m.),
1090(m.), 1037(m.), 956(m.), 864(w.), 827(m.), 772(m.), 759(m.), 709(s.), 663(s.), 628(vs.),
584(m.), 531(s.), 504(m.), 486(w.), 406(m.).
1H NMR (CDCl3, δ, ppm): 1.53 (s, H2O), 3.82 (s, 3H, Me), 4.83 (s, 2H, C5H4), 5.24 (s, 2H,
C5H4), 7.44-7.71 (m, 3H, C6H4), 8.03 (m, H, C6H4)
Elemental analysis for Mr = 366 g/mol
%C %H
Calculated: 55.75 3.02
Found:
55.57 3.12
2.6 Synthesis of 4-ferrocenylphthalazin-1(2Н)-one (V)
Protocol 1
N2H4×H2O (0.40 ml, 8.20 mmol) was added to orange solution of I (0.28 g, 0.85 mmol) in i-
PrOH (15 ml), and the mixture was refluxed for 12 h. The reaction was monitored with TLC
(acetone - EtOAc 4 : 1 v/v) until the disappearance of the starting acid was complete. Than the
reaction mixture was cooled to -4 °C to form an orange precipitate. The solution was filtered off,
and the precipitate was washed with cold i-PrOH (2×5 ml). The resulting product was further
purified by recrystallization from boiling MeOH.
A single crystal suitable for XRD was obtained by slowly cooling a solution of V in MeOH in a
sealed ampoule.
Yield: orange crystals, 0.21 g, 75%
Protocol 2
N2H4×H2O (0.14 ml, 2.87 mmol) was added to the orange solution of III (0.10 g, 0.287 mmol) in
i-PrOH (6 ml) and the mixture was refluxed for 6 h. The reaction was monitored with TLC
(Acetone - EtOAc 4 : 1 v/v) until complete disappearance of the starting ether. Then the reaction
mixture was cooled at a room temperature. The solvent was removed under reduced pressure.
The orange precipitate obtained was washed with cold i-PrOH.
Yield: orange powder, 0.08 g, 86 %,
Protocol 3
N2H4×H2O (2 ml, 42.60 mmol) was added to the orange solution of I (1.50 g, 4.50 mmol) in i-
PrOH (62 ml). The reaction mixture was heated in an autoclave for 18 h at 95°C. Then the
autoclave was slowly cooled to room temperature. The dark-red mother liquor was separated.
The black precipitate was extracted with i-PrOH (2×5 ml), and the orange solution obtained was

combined with the mother liquor. The solvent was removed under reduced pressure. The brown
oil obtained was washed with Et2O (3×10 ml). The product was crystallized from hot MeOH.
Yield: orange crystals, 0.82 g, 58 %
Protocol 4
The synthesis was similar to that in Protocol 3, with the exception of reaction time (48 h).
Yield: orange crystals, 1.38 g, 93 %
IR (v, cm-1): 3291(w.), 3199(w.), 3154(w.), 3136(w.), 3092(w.), 3018(w.), 2980(m.), 2928(w.),
2916(w.), 2877(w.), 2842(w.), 1638(vs.), 1608(s.), 1575(s.), 1496(m.), 1472(m.), 1409(m.),
1383(m.), 1351(s.), 1327(m.), 1307(m.), 1268(m.), 1225(m.), 1171(m.), 1153(m.), 1123(m.),
1105(m.), 1056(m.), 1024(m.), 1000(m.), 903(m.), 887(m.), 872(m.), 775(vs.), 726(m.), 686(vs.),
645(s.), 632(m.), 584(m.), 481(vs.), 453(s.), 405(m.).
1H NMR (d6-dmso, δ, ppm): 4.22 (s, 5H, C5H5), 4.50 (m, 2H, C5H4), 4.76 (m, 2H, C5H4), 7.88
(m, 1H, C6H4), 8.04 (m, 1H, C6H4), 8.31 (m, 1H, C6H4), 8.69 (m, 1H, C6H4).
13C NMR (d6- dmso, ppm): 159.06, 143.96, 133.20, 131.22, 129.03, 127.52, 126.71, 126.04,
81.33, 69.48, 69.14, 69.01, 48.55.
Elemental analysis for Mr = 330g/mol
%C %H %N
Calculated: 65.48 4.27 8.48
Found:
65.01 4.50 8.75
2.7 Synthesis of 4-cymantrenylphthalazin-1(2Н)-one (VI)
Method 1
N2H4×H2O (0.4 ml, 8.20 mmol) was added to a light-yellow solution of II (0.30 g, 0.85 mmol) in
i-PrOH (15 ml), and the mixture was refluxed for 9 h. The reaction was monitored with TLC
(acetone - EtOAc 4 : 1 v/v) until disappearance of the starting acid was complete. The reaction
mixture was cooled to -4 °C to form a pale-yellow precipitate. The solution was filtered off, and
the precipitate was washed with cold i-PrOH (2×5 ml).
A single crystal suitable for XRD was obtained by recrystallization of the product from hot
MeCN.
Yield: light-yellow powder, 0.22 g, 73 %,
Method 2
N2H4×H2O (0.4 ml, 8.20mmol) was added to the yellow solution IV (0.30 g, 0.82 mmol) in i-
PrOH (20 ml) and the mixture was refluxed for 1 h. The reaction was monitored with TLC
(acetone - EtOAc 4 : 1 v/v) until the disappearance of the starting ether was complete. Then the

reaction mixture was cooled at room temperature. The mother liquor is filtered off. The light-
yellow precipitate obtained was washed with cold i-PrOH.
Yield: light-yellow powder, 0.23 g, 82 %,
Protocol 3
N2H4×H2O (2 ml, 42.60 mmol) was added to the yellow solution of II (1.50 g, 4.26 mmol) in i-
PrOH (62 ml). The reaction mixture was heated in an autoclave for 18 hours at 95°C. Then the
autoclave was slowly cooled to room temperature. The colorless mother liquor was separated by
decantation. The crystal precipitate was washed with cold i-PrOH, and dried under reduced
pressure.
Yield: light-yellow crystals, 1.05 g, 70 %
Method 4
The synthesis is similar to that in Protocol 3 with the exception of the reaction time (48 h).
Yield: light-yellow crystals, 1.33 g, 90 %
IR (v, cm-1): 2997(m.), 2932(m.), 2897(m.), 2164(w.), 2033(s.), 1953(vs.), 1932(vs.), 1739(w.),
1666(s.), 1607(w.), 1553(w.), 1477(w.), 1344(m.), 1231(w.), 1157(w.), 1029(w.), 986(w.),
869(w.), 851(w.),842(w.), 785(m.), 729(w.), 684(w.), 664(m.), 633(s.), 590(w.), 536(m.),
428(w.),
1H NMR (d6-dmso, δ, ppm): 5.20 (m, 2H, Cp), 5.67 (m, 2H, Cp), 7.84-7.95 (m, 1H, C6H4), 7.98
(m, 2H, C6H4), 8.31(m, 1H, C6H4)
13C NMR (d6-dmso, δ, ppm): 224.97, 159.07, 138.86, 133.72, 131.83, 128.58, 127.21, 126.18,
125.68, 99.00, 86.26, 83.16, 48.58
Elemental analysis for Mr = 342 g/mol
%C %H %N
Calculated: 55.19 2.61 8.05
Found:
55.58 2.79 8.45
2.5. X-ray crystallography
X-ray diffraction data were collected using a Bruker SMART CCD diffractometer.
Crystallographic data and structure refinement details for structures V and VI are listed in
Table 1. Absorption correction was applied using the program SADAB [[12]]. Using Olex2
[[13]], the structures were solved with ShelXS program [[14]] by direct methods and refined
with ShelXL [[15]] program using Least Squares refinement on F2. All non-hydrogen atoms
were refined anisotropically. Hydrogen atoms were positioned geometrically using a riding
model with fixed isotropic thermal factors on carbon atoms. Hydrogen atoms of NH groups were
refined with isotropic thermal parameters.

Table 1. Crystal data and structure refinement for compounds V and VI.
Parameter
V
VI
M
Radiation (λ, Å)
Temperature, K
Space group
а, (Å)
330.16
348.19
MoKα (λ = 0.71073)
150
150
P-1
P21/n
9.8419(2)
10.4329(2)
14.6051(3)
90
6.8627(2)
7.4687(2)
14.7430(4)
85.9450(10)
78.8932(10)
71.3360(9)
702.48(3)
2
b, (Å)
c, (Å)
α, (°)
β, (°)
107.4770(10)
90
γ, (°)
V, Å3
1430.42(5)
4
Z
ρcalc, g/cm–3
μ, mm–1
1.533
1.646
1.056
0.962
F(000)
680.0
352.0
2Θ range for data collection (°)
Measurement method
Number of independent
reflections, (N1)
Number of reflections I >2σ(I)
(N2)
4.878 to 70.332
5.632 to 55.712
ω
6087 [Rint = 0.0302,
Rsigma = 0.0253]
5236
3289 [Rint = 0.0204,
Rsigma = 0.0245]
3.072
Parameters
GOОF (F2)
R1 for N2
203
1.048
212
1.068
0.0338
0.0846
0.49/-0.35
0.0287
0.0723
0.41/-0.24
wR2 for N1
Δρmax/Δρmin, e Å–3
2.6. Electrochemical study of complexes III and V.
Cyclic voltammograms (CVs) of complexes III and V were recorded on a PAR 273
potentiostat/galvanostat (Princeton Applied Research) with a standard software. The

measurements were carried out in a thermostatically controlled three-electrode electrochemical
cell in a high-purity argon atmosphere. A SU_2000 (0.0078 cm2) glassy carbon disk pressed in
Teflon served as working electrode and a platinum plate (1 cm2) was auxiliary electrode. The
potentials were measured versus an Ag quasi-reference electrode in the same solution. The
potential of the Fc/Fc+ couple versus Ag in the same solution is ~ 0.20 V [[16]].
The measurements were carried out in dichloromethane with 0.2 M Bu4NPF6 as supporting
electrolyte. The CVs were recorded in the range of the potentials (1.7 ÷ -1.9) V. Reversible
waves on cyclic voltammograms were recorded with a different sweep rates in the interval 0.1 to
1.0 Vs-1.
3. Results and discussion
o-Ferrocenylcarbonylbenzoic acid (I) and o-cymantrenylcarbonylbenzoic acid (II) were
obtained by the Friedel-Crafts reaction from ferrocene or manganese cyclopentadienyl
tricarbonyl (cymantrene) with phthalic anhydride (Scheme 1).
OH
O
OH
O
O
O
O
1. FcH, AlCl3
2. HCl
1. C5H5Mn(CO)3, AlCl3
2. HCl
O
Fe
Mn
CO
OC
CO
O
II
I
Scheme 1.
Earlier, bis-o-carboxybenzoylferrocene was obtained and characterized as its dimethyl
ester [[17]]. The reaction of ferrocene with phthalic anhydride was also mentioned by
Nesmeyanov [[18]] and described by Qi Shuai [[19]]. Compound II was reported earlier [[20]]
without experimental data. Similar reaction of C5H5Mn(CO)3 with succinic anhydride results in
cyclopentadien-1-yl-(3-carboxylato-1-oxopropyl) manganese tricarbonyl [[21]]. It was
conjugated to cell-penetrating peptides (CPPs) for diagnostic imaging and therapeutic
applications in human medicine. o-Cymantrenylcarbonylbenzoic acid is worse soluble in CH2Cl2
compared to the ferrocene analogue and can be easily separated from the reaction mixture
without column chromatography. IR spectra of both corresponding acids showed a strong
absorbance band at ~1665 cm−1 due to the carbonyl stretching vibration of C=O group between
benzene and cyclopentadienyl rings.
The esterification reactions of organometallic acids I and II were carried out using
dimethyl carbonate (DMC) as a “green” methylating agent in the presence of DBU as a strong
non-nucleophilic base (Scheme 2). The main advantage of DMC compared to other methylating

reagents such as methyl iodide and dimethyl sulfate is its low toxicity and biodegradability
[[22]].
OH
O
O
O
O
O
DMC
DBU
Fe
Fe
III
I
OH
O
O
O
O
O
DMC
DBU
Mn
CO
Mn
CO
OC
CO
OC
CO
IV
II
Scheme 2.
The IR spectra of methyl o-ferrocenylcarbonylbenzoate FcC(O)C6H4COOMe (III)
contains two bands of carbonyl stretching vibration C=O (1714 and 1665 cm-1), as well as
manganese analogue methyl o-cymantrenylcarbonylbenzoate (CO)3MnC5H4C(O)C6H4COOMe
(IV) (1714 and 1665 cm-1).
Different routes can be used for the preparation of the organometallic phthalazin-1(2H)-
ones, such as 4-ferrocenylphthalazin-1(2H)-one (V) and 4-cymantrenylphthalazin-1(2H)-one)
(VI) (Scheme 3).
OH
O
OH
O
O
O
Fe
Mn
CO
N
OC
CO
2 H
4
i
-
P
r
O
H 4
N 2
x
u
H
l
f
,
e
r
r
e
,
H
f
l
I
NH
u
N
O
r
x
II
P
-
i
R
O
DMC,
DBU
DMC,
DBU
O
O
N
O
O
O
2 H
O
4
i
H 4
N 2
-
P
r
O
x
H
u
l
f
,
R = (CO)3MnC5H4,
C5H5FeC5H4
r
e
f
e
r
,
l
u
H
x
O
r
P
-
i
Fe
Mn
CO
OC
CO
III
IV
Scheme 3.
Firstly, compounds V and VI can be obtained by prolonged reflux of acids I and II with
hydrazine hydrate (Protocol 1). The corresponding methyl ester reactions (Protocol 2) with

hydrazine hydrate also result in the same compounds with higher yields and rates, because -
OCH3 is the better leaving group than –OH (Table 2). However, the organometallic phtalazinone
synthesis via ester is a two-stage reaction, so the total yield is lower than that in the first
Protocol.
If the interaction of I and II with hydrazine hydrate is carried out in an autoclave,
compounds V and VI can be obtained in high yield (method 3). When the reaction time reaches
48 hours, yields increase to more than 90 % (Protocol 4).
Substrate
Condition
reflux
Time, h
12
Yield, %
75
o-Ferrocenylcarbonylbenzoic acid
o-Ferrocenylcarbonylbenzoic acid
o-Ferrocenylcarbonylbenzoic acid
solvothermal
synthesis
18
48
58
93
solvothermal
synthesis
Methyl o-ferrocenylcarbonylbenzoate
reflux
reflux
6
9
86
73
o-Cymantrenylcarbonylbenzoic acid
o-Cymantrenylcarbonylbenzoic acid solvothermal
synthesis
18
48
1
70
90
82
o-Cymantrenylcarbonylbenzoic acid solvothermal
synthesis
Methyl o-cymantrenylcarbonylbenzoic
reflux
acid
Table 2. Preparation of organometallic phthalazin-1(2H)–ones.
The structures of 4-ferrocenylphthalazin-1(2H)-one and 4-cymantrenylphthalazin-1(2H)-one
were established by X-ray diffraction. The structural data of the compounds obtained can be
compared with the structure of the unsubstituted phthalazin-1(2H)-one [[23]].

Fig. 2. Molecular structure of complex V. The most important bond length (Ǻ): O1-C1
1.244(1), N2-N1 1.366(1), N2-C1 1.355(1), N1-C8 1.310(1), C7-C8 1.455(1), C7-C2
1.405(2), C8-C9 1.477(2) C2-C1 1.459(1).
Fig. 3. Molecular structure of complex VI. The most important bond length (Ǻ):
O4-C10 1.245(2), N2-N1 1.364(2),N2-C9 1.300(2), N1-C10 1.363(2), C16-C9 1.457(2)
C16-C11 1.409(2), C10-C11 1.456(2), C9-C4 1.479(2)
Fig. 4. Intermolecular double hydrogen bonds in phtalazinone dimers V (N(2)-O(1)i 2.810(1) Ǻ)
and VI (N(1)-O(4)i 2.820(2) Ǻ).

Phthalazin-1(2H)-ones V and VI form dimers with intermolecular hydrogen bonds
(N∙∙∙O distances are 2.810(1) for ferrocenyl- and 2.820(2) for cymantrenyl derivatives), which
are slightly shortened compared to the unsubstituted phthalazin-1 (2H) –one (N∙∙∙O 2.842(2) Å)
(Fig. 3). Angles between cyclopentadienyl and heterocyclic rings are 30° for V and 34° for VI.
The IR spectra of V and VI contain characteristic bonds of carbonyl stretching vibration C=O
(1638 cm-1 for V and 1666 cm-1 for VI). The characteristic νCO stretching vibrations observed
for cymantrenyl fragment increase from 2019 and 1926 for II to 2033, 1953 and 1932 for VI.
The CVs for complexes III and V are presented at Fig. 5 and 6. For complex III one can
observe two one-electron oxidation waves. The first wave at the peak potential 0.38 V ( A) is
reversible with (ΔEp = 60 mV) and the second wave at the peak potential 1.47 V (B) is
irreversible, being associated with the oxidation of benzoate fragment. For complex V in the
wide range of the potentials there is an only one-electron reversible wave at the peak potential
0.23 V (ΔEp = 60 mV). For both complexes there are one-electron reversible oxidation waves
connected with the ferrocene unit. Redox separation between reversible waves of complexes III
and V is ΔE°′ = 150 mV. Such separation in redox processes of III and V may be due to the
electron-acceptor properties of carbonylbenzoate fragment. In the cathodic range of the
potentials one can not observe well-defined waves of the reduction for complexes III and V up to
potential -1.9 V.
I/A
4
60
20
15
10
5
3
2
I / A
A
40
20
0
B
A
1
-20
-40
-0,4
-0,2
0,0
0,2
0,4
0,6
0,8
E/Vvs. Ag
0
-5
-10
-2
-1
0
1
2
E / V vs.Ag
Fig. 5. CVs of complex III (C= 3.5 mM) recorded at the GC electrode SU _2000 (0.0078 cm2) in
dichloromethane deaerated by high-purity argon with 0.2 M Bu4NPF6 as the supporting
electrolyte in the potential range (-1.9 ÷ 1.7) V at the potential sweep rate 0.1 V s-1 and the wave

(A) recorded in interval potentials (-0.25 ÷ 0.7) V with a different sweep rate, V s-1: 1- 0.1; 2-
0.2; 3-0.5; 4- 1.0
I / A
50
4
40
3
30
2
20
1
10
0
-10
-20
-30
-40
-0,6
-0,4
-0,2
0,0
0,2
0,4
0,6
0,8
E / V vs. Ag
Fig. 6. CVs of complex V (C= 3.2 mM) recorded at the GC electrode SU _2000 (0.0078 cm2) in
dichloromethane deaerated by high-purity argon with 0.2 M Bu4NPF6 as the supporting
electrolyte) in interval potentials (-0.45 ÷ 0.7) V with a different sweep rate, V s-1: 1- 0.1; 2- 0.2;
3-0.5; 4- 1.0.
Conclusion
Hence, we synthesized o-cymantrenylcarbonylbenzoic and ferrocenylcarbonylbenzoic acid
methyl esters. Cyclic voltammetric measurement of the latter revealed that irreversible one-
electron oxidation is associated with the oxidation of benzoate fragment. Cymantrene- and
ferrocene-containing phthalazin-1(2H)-ones were prepared from the corresponding carboxylic
acids and their methyl esters. All ferrocene derivatives undergo a reversible one-electron
oxidation localized presumably at the ferrocene unit. Solvothermal conditions of organometallic
phthalazin-1(2H)-ones were optimized. All compounds were characterized by spectroscopic
methods and the molecular structures of 4-ferrocenylphthalazin-1(2H)-one and 4-
cymentrenylphthalazin-1(2H)-one were confirmed by X-ray structural analysis.
Acknowledgements
This research was performed using the equipment of the JRC PMR IGIC RAS. This work
was supported by the Russian Science Foundation (grant 18-73-10206)
Appendix A. Supplementary data

CCDC 1901244 and 1901245 contain the supplementary crystallographic data for compounds V
and VI, correspondingly. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-
033; or e-mail: deposit@ccdc.cam.ac.uk.
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