Redox Cascades and Making of a C-C Bond: 1,2-Benzodiazinyl Radicals and a Copper Complex of a Benzodiazine

Article abstract of DOI:10.1021/acs.joc.8b02858

Two 1,2-benzodiazinyl radicals, cinnolinyl radicals by name, were successfully isolated by cascade routes using 1,4-naphthoquinone as a precursor. Reaction of 1,4-naphthoquinone with hydrazine hydrate promotes a (5e + 5H⁺) redox cascade affording benzo[g]naphtho[1,2-c]cinnolinyl-7,12,14-trione (Cn^·) in 69% yields, while the similar reaction with 2-hydrazinopyridine is a (7e + 7H⁺) oxidative cascade and furnishes N-pyridinecinnolinyl radical (^PyCn^·). The cascades are composed of C-N and C-C bond making reactions. The neutral even alternate arenes are always diamagnetic; thus, the isolation of Cn^· and ^PyCn^· is a breakthrough. The Cn^·/Cn^- and ^PyCn^·/^PyCn^- redox couples are reversible, and the reaction of Cn^· with [Cu^I(PPh₃)₃Cl] in the presence of hydrazine hydrate and Et₃N affords a Cn^- complex of copper(I), [(Cn^-)Cu^I(PPh₃)₂] (1). Similar to phenalenyl radical, ^PyCn^· exists in three redox states, ^PyCn^+PyCn^·, and ^PyCn^-, in a smaller potential range (-0.30 V to -0.60 V vs Fc⁺/Fc couple) and can be used as an oxidant as well as a reductant. ^PyCn^· acts as a catalyst for the oxidative cleavages of benzil to benzoic and 2,2′-pyridil to picolinic acids in methanol in the presence of air. The molecular and electronic structures of Cn^·PyCn^·, and 1·1/2MeOH were confirmed by single crystal X-ray crystallography, EPR spectroscopy, and DFT calculations.

Full text of DOI:10.1021/acs.joc.8b02858

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Article
Redox Cascades and Making of a C-C Bond: 1,2-Benzodiazinyl
Radicals and a Copper Complex of a Benzodiazine
Sandip Mondal, Sachinath Bera, and Prasanta Ghosh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02858 • Publication Date (Web): 21 Jan 2019
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Redox Cascades and Making of a C-C Bond: 1,2-
Benzodiazinyl Radicals and a Copper Complex of a
Benzodiazine
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Sandip Mondal, Sachinath Bera and Prasanta Ghosh*[a]
Department of Chemistry, R. K. Mission Residential College, Narendrapur, Kolkata 103, West Bengal,
India
E-mail: ghosh@pghosh.in
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ABSTRACT
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Two 1,2-benzodiazinyl radicals, cinnolinyl radicals by name, were successfully isolated by cascade
routes using 1,4-naphthoquinone as a precursor. Reaction of 1,4-naphthoquinone with hydrazine hydrate
promotes a (5e + 5H+) redox cascade affording benzo[g]naphtho[1,2-c]cinnolinyl-7,12,14-trione (Cn●)
in 69% yields, while the similar reaction with 2-hydrazinopyridine is a (7e + 7H+) oxidative cascade
and furnishes N-pyridinecinnolinyl radical (PyCn●). The cascades are composed of C-N and C-C bond
making reactions. The neutral even alternate arenes are always diamagnetic, thus the isolation of Cn●
and PyCn● is a breakthrough. The Cn●/Cn- and PyCn●/PyCn- redox couples are reversible and the reaction
of Cn● with [CuI(PPh3)3Cl] in presence of hydrazine hydrate and Et3N affords a Cn- complex of
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Py
Py
copper(I), [(Cn-)CuI(PPh3)2] (1). Similar to phenalenyl radical, Cn● exists in three redox states, Cn+
,
PyCn● PyCn- in a smaller potential range (-0.30 V to -0.60 V vs Fc+/Fc couple) and can be used as an
,
Py
oxidant as well as a reductant. Cn● acts as a catalyst for the oxidative cleavages of benzil to benzoic
and 2,2'-pyridil to picolinic acids in methanol in presence of air. The molecular and electronic structures
of Cn●, PyCn● and 1.½MeOH were confirmed by single crystal X-ray crystallography, EPR spectroscopy
and DFT calculations.
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Introduction
Paramagnetic neutral odd alternate hydrocarbon (OAH) where the unpaired electron resides on a non
bonding molecular orbital is a threshold in designing non metal super conductors proposed by Haddon.1
In this regard phenalenyl, an OAH was explored widely in elucidating super conductivity,2 catalytic
activity,3 designing memory devices4 and the results are promising in many cases. The growth of
hydrocarbon radical chemistry visited is based on the skeleton constituted of phenalenyl fragment. The
neutral even alternate hydrocarbons which are abundant are diamagnetic and lack this important feature.
However, the scope remains open for the hetero-arene incorporating NH functions that are oxidizable to
N● as established in case of Blatter radical.5 In such cases neutral even alternate hetero-arene can be
paramagnetic. In this study, the same was established by isolating two neutral even alternate
paramagnetic hetero-arenes as 1,2-benzodiazinyl radicals. Benzodiazines are a class of azine
compounds that exhibit diverse biological activities.6 These were worthy in medicinal and agro-
chemistry.7 Several routes were developed in synthesizing benzodiazine derivatives.8 However, no
paramagnetic benzodiazine derivative is reported so far.
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In this investigation we succeeded to design redox cascades that furnish hither-to-unknown 1, 2-
benzodiazinyl radicals. Cascades that have high atom economy with lower chemical waste are worthy in
devoloping the syntheses of functional organic molecules.9 However, examples of redox cascades are
limited in scope.10 Recently we have disclosed that 1,4-naphthoquinone derivatives are precursors of
redox cascades.11 In this particular search, two stable 1, 2 benzodiazinyl radicals as illustrated in Chart
1, benzo[g]naphtho[1,2-c]cinnolinyl-7,12,14-trione (Cn●) and N-pyridinecinnolinyl (PyCn●) radicals by
name were successfully isolated in high yields exploiting 1,4-naphthoquinone as a precursor. It is
noteworthy that Cohen in 1966 claimed that 1, benzo[g]naphtho[1,2-c]cinnoline-7,12,14-trione (CnH)
was isolated from a reaction of 1,4-naphthoquinone with hydrazine hydrate in methanol.12a Pummerer
et.al. in 1929 also reported the isolation of CnH from a reaction of 2,2’-dinaphthoqinone with hydrazine
hydrate.12b Both of them considered that they had isolated the diamagnetic CnH with a para magnetic
impurity and missed to assign the Cn●. In this report, it is disclosed that reaction of 1,4-naphthoquinone
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with hydrazine hydrate in air promotes a redox cascade affording Cn● as a major product, no CnH was
isolated from this reaction. The similar reaction of 1,4-naphthoquinone with 2-hydrazinopyridine yields
PyCn●. The structural skeletons of Cn● and PyCn● are different, the former contains an 1,4-iminoquinone
fragment. The redox activity of Cn● is notably different from PyCn● that resembles with the chemistry of
phenalenyl. Notably, the properties of Cn● and PyCn● are different from common hydrazyl radicals.13
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Chart 1. Isolated 1, 2-Benzodiazinyl Radicals and a Copper Complex
Cn●
PyCn●
1
Isolation of a stable cinnolinyl radical that belongs to an even alternate hydrocarbon family is a
milestone to the growth of the chemistry of neutral paramagnetic aromatics and designing functional
materials and devices. The preliminary investigation establishes that PyCn● acts as a catalyst for the
oxidative cleavage of benzil to benzoic acid in methanol in presence of air. Oxidative cleavage of benzil
to benzoic acid is not common, generally in presence of base benzil undergoes rearrangement to benzilic
acid.14 Thus, modelling of a catalyst for this redox reaction is significant in metallo-organic chemistry
and in this regard, the activity of PyCn● is worthy.
Transition metal complexes of Cn● will be a venue to stabilize other redox states of it and to open up
the possibilities of their inter-conversions detecting the spectral and structural features and the activities.
In this context, the first benzodiazinate complex of a transition metal ion is reported. In this particular
study, a cinnolinate (Cn-) complex of copper(I), of type [(Cn-)CuI(PPh3)2] (1) was isolated and
characterized. The molecular and electronic structures of Cn●, PyCn● and 1 were confirmed by single
crystal X-ray crystallography, EPR spectroscopy, cyclic voltammetry and density functional theory
(DFT) calculations.
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Results and Discussion
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Details of the syntheses of Cn●, PyCn● and 1 and their characterization data are outlined in the
Experimental Section (vide infra). Reaction of 1,4-naphthoquinone with hydrazine in methanol
promotes a redox cascade affording Cn● in 69% yields. The plausible path of the cascade are shown in
Scheme 1. The reaction procedes via 1,4 addition reaction of hydrazine to 1,4-naphthoquinone followed
by tautomerization affording A. In presence of air as an oxidizing agent, A undergoes oxidation,
tautomerization, oxidation, condensation and further oxidation furnishing Cn●. The conversion of A to
Cn● in air is faster and no intermediate of this transformation has been successfully detected. In the ESI
mass spectrometry, the reaction mixture just after 2 min gives a single m/z peak at 325 due to Cn●
(Figure S1). In presence of air, the reaction produces H2O2 which was detected chemically by recating
with KI solution evolving I2. In presence of starch, the broader Uv-vis absorption band at 600 nm of the
reaction mixtute (Figure S2) infers the formation of a starch-I2 complex.15a It is similar to the
antharaquinone process of H2O2 production.15b The study concludes that the conversion of 1,4-
naphthoquinone to Cn● in presence of hydrazine is a redox reaction. It is overall a (5e + 5H+) oxidative
coupling reaction as given in eq 1.
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1,4-Naphthoquinone + NH2NH2 + 2O2 = Cn● + 5/2 H2O2 + H2O
(1)
However, in absence of air the reaction is slower and different as depicted in Scheme 1. Analysis of
the reaction mixture under argon by ESI mass spectrometry confirmed the formation of A and a
hydroquinone derivative B as given in Figure S3. In presence of I2 B undergoes oxidation to C that
gives the product Cn●, where I2 is reduced to iodide. Pummerer et.al.12b established that C is a precursor
of Cn●, supporting the notion of formation of C as an intermediate of this oxidative coupling reaction in
presence of air and I2. The formation of iodide was authenticated by detecting mass peaks due to iodide
and a monoiodo adduct of Cn● in ESI mass spectrometry (Figure S4). The study infer that the
conversion of 1,4-naphthoqione → Cn● in presence of hydrazine needs an oxidizing agent.
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Scheme 1. Redox Cascade and Formation of Cn●
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The similar reaction with phenylhydrazine produces naphthalene-1,4-diol evolving nitrogen gas,
while the reaction of 1,4-naphthoquinone with less reducing 2-hydrazinopyridine promotes a different
cascade affording PyCn● in 71% yields. It is a (7e+7H+) oxidative dimerization of two 1,4-
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naphthoquinone units bridged by hydrazinopyridine fragment. The cascade is composed of 1,4 addition
reaction (C-N bond formations),
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Scheme 2. Redox Cascade and Formation of PyCn●
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Py
Py
Py
O
O
O
O
OH
OH
Tautomeri
zation
H
N
H
-(2e + 4H+)
H2N
N
H
N
N
N
1,4 addition
H
H
O
O
OH
OH
OH
O
OH
O
Py
Py
Py
O
O
O
O
O
O
Radical
coupling
H
N
H
N
H
-(4e + 2H+)
N
Tautomerization
N
N
N
H
H
O
O
O
O
OH
O
OH
O
Py
Py
Py
O
O
O
H
N
N
N
N
-(e + H+)
N
N
O
O
O
O
O
tautomerization, oxidation, radical coupling (C-C bond formation) reactions, and oxidation of amine to
aminyl radical as depicted in Scheme 2. The intermediates of these reactions were analyzed by ESI mass
spectrometry. The concerted 1,4-addition of the hydrazine derivative with two 1,4-naphthoquinones
were authenticated by ESI mass spectrometry of the solution obtained after 5 min of both reactions (see,
Figure S5). Notably no mass peak due to mono hydrazine-1,4-naphthoquinone derivative was detected.
The reaction of Cn● with [CuI(PPh3)3Cl] in presence of Et3N in a mixture of methanol and
dichloromethane solvents does not yield any isolable product, however the same reaction in presence of
hydrazine hydrate at room temperature affords green crystals of 1 in 57% yields. In this reaction,
hydrazine acts as a reductant converting Cn● to Cn-. The reaction is expressed by eq 2.
Cn● + [Cu(PPh3)3Cl] + ¼ N2H4 + Et3N = [(Cn-)CuI(PPh3)2] (1) + [HEt3N]+Cl- + PPh3 + ¼ N2
(2)
X-ray Crystallography. PyCn● and 1.1/2MeOH crystallize respectively in P-1 and P21/C space
groups (CCDC 1835620 and 1872411). The molecular geometries in the crystal forms and the atom
labeling scheme are illustrated in Figure 1, Figures S6(a) and S6(b). The crystallographic data are
summarized in Table S1. The selected bond parameters are listed in Table 1. In PyCn●, the N(1)-N(2)
length is 1.367(2) Å that corresponds well to that of the zwitterionic triphenylphosphonio-hydrazyl
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radical reported recently.11 The N(1)-C(2) length, 1.291(2) Å is relatively shorter due to the conjugation
of the singly occupied p orbital of the N(1) atom with the benzoquinone fragment. For the same reason
the C(2)-C(3) and C(4)-O(2) lengths are relatively longer than C(11)-C(12) and C(1)-O(1) lengths. The
N(2)-C(11) is 1.371(2) Å. The non-bonded distance between two successive layers in PyCn● is 3.360 Å,
implying that no significant interaction between two paramagnetic units is present in crystals and the
same was authenticated by EPR spectroscopy.
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For comparison, the bond parameters of PyCn● in gas phase were elucidated by hybrid B3LYP DFT
method. The gas phase geometry of PyCn● was optimized with doublet spin state using 6-31+G(d,p)
basis set and calculated bond parameters are listed in Table 1. The calculated lengths except C(3)-C(4)
length, correlate well with those obtained from single crystal diffraction study. Notably, both calculated
and experimental N-N lengths of PyCn● are relatively longer than N=N length due to localization of the
unpaid electron. The N-N length in azo anion radicals lies in the range of 1.33-1.34 Å.16
We failed to isolate the single crystals for X-ray diffraction study of Cn●. However, a Cn- complex of
copper(I) as in 1.½MeOH has been structurally characterized. The X-ray bond parameters of PyCn● and
Cn- in 1.½MeOH are notably different. The CuP2NO tetrahedron of 1.½MeOH is distorted. In
1.½MeOH the N(1)-N(2) length, 1.341(3) Å, is relatively shorter than that in PyCn●. The N(1)-C(2)
length is an intermediate between C-N single and double bonds. The C(3)-C(12) length is also shorter
than a Csp2-Csp2 length. The features can be analyzed by the resonance structures of Cn- as given in
Chart 2, where the E and F forms are aromatic in nature. Due to the resonance contribution, the C(14)-
O(3) length is relatively longer than C(1)-O(1) and C(4)-O(2) lengths. The 1,4-naphthoquinone is a
weaker ligand and the Cu-O(1) length, 2.247(2) Å is significantly longer than the Cu-N(1) length, 2.012
(2) Å. Because of the coordinated anionic ligand, the Cu(I) → PPh3 back-bonding is stronger and the
average Cu-PPh3 lengths, 2.238 (1) Å, are relatively shorter than those recorded in
bis(triphenylphosphine) complexes of copper(I) containing neutral polypyridyl ligands. For example, in
[Cu(PPh3)2dppz]NO3 (dppz = dipyridophenazine), the average Cu-PPh3 lengths are 2.271(1) Å.17
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Chart 2. Resonance Structures of Cn-
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(a)
(b)
Figure 1. Molecular geometries of (a) PyCn● and (b) 1.½MeOH in crystal forms (40% thermal
ellipsoids, hydrogen atoms and solvent molecule are omitted for clarity).
Table 1. Selected Experimental and Calculated Bond Lengths of (Å) of PyCn●
Exptl
Calcd
1.359
1.313
1.427
1.465
1.221
1.301
Exptl
Calcd
1.430
1.220
1.223
1.390
1.380
1.501
N(1)-N(2)
N(1)-C(2)
C(2)-C(3)
C(3)-C(4)
C(1)-O(1)
C(4)-O(2)
1.367(2)
1.291(2)
1.465(2)
1.367(2)
1.212 (2)
1.346(2)
C(3)-C(12)
1.487(2)
O(3)-C(13) 1.238(2)
O(4)-C(20) 1.212(2)
N(2)-C(11) 1.371(2)
C(11)-C(12) 1.368(2)
C(12)-C(13) 1.473(2)
The bond parameters of 1, 1+, Cn● and CnH were calculated by hybrid PBE0 DFT method to establish
the trend of bond lengths of different redox forms. The gas phase geometries of 1 and CnH were
optimized with singlet spin state, while those of 1+ and Cn● were optimized with doublet spin state. The
calculated bond lengths are summarized in Table 2. The calculated N-N lengths of 1 and CnH are
similar. In the conversion of 1 → 1+, no significant changes of Cu-N(1), Cu-O(1) and Cu-P lengths were
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observed. Notably, the calculated N-N lengths of 1+ and Cn● are comparable, inferring that 1+ is a
copper(I) complex of Cn●.
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Table 2. Selected Experimental Bond Lengths of (Å) of 1.½MeOH and Calculated Bond Lengths of (Å)
1, 1+, Cn● and CnH
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Exptl
Calcd
Cn●
1.½MeOH
Cu-N(1)
CnH
1
1+
2.012 (2)
2.247(2)
2.262(2)
2.214(2)
1.341(3)
1.344(3)
1.396(3)
1.473(4)
1.230(5)
1.222(3)
1.437(3)
1.327(3)
1.443(4)
1.390(4)
1.414(4)
1.256(4)
2.046
2.254
2.324
2.272
1.326
1.399
1.398
1.463
1.232
1.223
1.449
1.327
1.462
1.377
1.445
1.228
2.025
2.246
2.324
2.297
1.314
1.348
1.393
1.498
1.227
1.213
1.426
1.315
1.447
1.400
1.456
1.224
Cu-O(1)
Cu-P(1)
Cu-P(2)
N(1)-N(2)
N(1)-C(2)
C(2)-C(3)
C(3)-C(4)
C(1)-O(1)
C(4)-O(2)
C(3)-C(12)
N(2)-C(11)
1.309
1.329
1.344
1.382
1.485
1.222
1.225
1.458
1.308
1.475
1.375
1.450
1.237
1.344
1.401
1.504
1.217
1.222
1.429
1.340
1.439
1.412
1.455
1.238
C(11)-C(12)
C(12)-C(13)
C(13)-C(14)
C(14)-O(3)
Redox Activity. The redox activities of Cn●, 1 and PyCn● were investigated by cyclic voltammetry in
acetonitrile at RT using tetrabutylammonium hexafluorophosphate as a supporting electrolyte and the
potential data referenced to Fc+/Fc couple are listed in Figure 2. The cyclic voltammogram of Cn●
displays two cathodic waves respectively at -1.14 and -1.56 V (Figure 2(a)) due to Cn●/Cn- and Cn-
/Cn●2- redox couples (Scheme 3).
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Figure 2. Cyclic voltammograms of (a) Cn●, (b) 1 and (c) PyCn● in acetonitrile using
tetrabutylammonium hexafluorophosphate as a supporting electrolyte (Potential referenced to Fc+/Fc
couple ).
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The cyclic voltammogram of 1 is exactly similar to that of Cn● (Figure 2(b)), precluding the mixing
of the metal with benzodiazine ligand. The anodic Cn●/Cn- redox couple of 1 appears at -1.12 V, while
the same for free Cn● is observed at -1.14 V. The cathodic Cn- /Cn2- redox wave of 1 appears at -1.44 V.
The redox activity of PyCn● is different from Cn● and 1 (Figure 2(c)). Notably, the cyclic
voltammogram of PyCn● is similar to that of phenalenyl. PyCn● exhibits a reversible anodic wave at -
0.34 V due to PyCn+/PyCn● redox couple. The first cathodic wave at - 0.61 V due to PyCn●/PyCn- is quite
reversible, while the second cathodic wave at -0.86 V due to 1,4-naphthoquinone/1,4-
naphthosemiquinonate anion radical redox couple is not reversible. In comparison to Cn●/Cn- redox
Py
Py
couple, the Cn●/PyCn- couple is positively shifted by 0.53 V, inferring that Cn● is stronger reducing
than Cn●. Similarly the second cathodic wave due to quinone reduction is positively shifted by 0.70 V.
Py
The study infers that Cn● is an oxidizing as well as a reducing agent. It exists in three redox states as
PyCn+, PyCn● and PyCn- as depicted in Scheme 3, in a smaller potential range (-0.30 to -0.60 V) and
PyCn● is a stable state and isolable in air.
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Scheme 3. Redox Series of Cn● and PyCn●
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EPR Spectroscopy and DFT Calculations. The X-band EPR spectrum of the powder sample of Cn●
exhibits a strong signal at g = 2.002 as illustrated in Figure 7(a), correlating well with those of organic
radicals.18 The isotopic signal of Cn● in CH2Cl2 at g = 2.003 (Figure S7(b)) does not reveal any
hyperfine splitting. The fluid solution EPR spectrum of 1+ obtained from a constant potential (at -0.80
V) bulk electrolysis experiment in CH2Cl2 displays a strong EPR
(a)
(b)
Figure 3. X-band EPR spectra of PyCn● (a) powder Sample at 295 K (b) CH2Cl2 solution at 295 K.
(Experimental, black and simulated, red).
signal at g = 2.0014 (Figure S7(c)), authenticating that 1+ is a Cn● complex of copper(1). The powder
sample spectrum of PyCn● displays a strong signal at g = 2.003 (Figure 3(a)). The fluid solution
spectrum of PyCn● shows a hyperfine splitting due to 14N nucleus (I = 1, AN = 6.4 G) as depicted in
Figure 3(b). However, the frozen glass spectrum of PyCn● with a signal at g = 2.003 does not display any
hyperfine splitting.
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The spin density distributions of Cn● and PyCn● obtained from Mulliken spin population analyses are
illustrated in Figures 4(a) and 4(b). In both cases the spin is dominantly localized on the benzodiazine
ring. In Cn●, the alpha spin scatters on N(1) (18%), C(3) (27%) and C(11) (15%) atoms, while the beta
spin disperses on the alternate C(2), C(12) and N(2) atoms. In addition the alpha spin is significantly
localized on C(3) (61%) and O(3) (26%) atoms. In case of PyCn●, the maximum alpha spin bearing atom
is C(3) carbon (41%) and the rest is localized on N(1), N(2), C(11) and O(2) atoms, while the beta spin
is localized on C(2) and C(12) atoms. It implies that the benzodiazine ring actively participate in both
oxidation and reduction reactions. Formation of a C-C sigma bond enhances the quenching of the
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Py
phenalenyl radical, however in case of Cn● no dimerization occurs as the C(3) atom is a member of
two fused rings. Two significant frontier molecular orbitals of PyCn●, SOMO and beta-LUMO of this
unique hetero-arene dominantly disperse on the benzodiazine ring, while the alpha-LUMO scatters on
one of the 1,4-naphthoquinone fragments as depicted in Figure S8.
(a)
(b)
(c)
Figure 4. Spin density plots of (a) Cn● (N1, 0.18; N2, -0.08; C2, -0.11; C3, 0.23; C11, 0.17; C12, -0.20;
C13, 0.61; O3, 0.26), (b) PyCn● (N1, 0.23; N2, 0.16; C3, 0.41; C11, 0.12; O2, 0.15) and (c) 1+ (N1, 0.15;
N2, -0.08; C2, -0.13; C3, 0.27; C11, 0.15; C12, -0.20; C13, 0.59; O3, 0.25) obtained from Mulliken spin
population analyses.
Py
It is noteworthy that the calculated electron affinity of Cn● is relatively larger (2.69 eV), while the
calculated ionization energy is smaller (6.50 eV) and comparable to those of alkaline earth metals. The
calculated energies of the frontier molecular orbitals of PyCn+, PyCn● and PyCn- are depicted in Figure 5.
Py
Py
Py
The HOMO of Cn+ is stabilized by 8.74 eV than that of Cn-. Similarly, the LUMO of Cn+ is 7.43
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eV lower in energy than that of PyCn-. The energy of SOMO of PyCn● is an intermediate between that of
the HOMOs of PyCn+ and PyCn-. The analysis predicts that PyCn● is a stronger reducing agent and the
same was established by cyclic voltammetry and chemical activities.
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Figure 5. Relative calculated energies of the frontier molecular orbitals of PyCn+, PyCn● and PyCn-.
The calculated bond lengths of 1 and CnH are summarized in Table 2. The calculated bond lengths of
Cn- in 1 correlates well with those of CnH, particularly the N(1)-N(2) lengths are 1.326 and 1.329 Å
respectively in 1 and CnH. However, the bond lengths of the benzodiazine ring in 1+ are similar to those
of Cn●. The N(1)-N(2) lengths of 1+ and Cn● are 1.314 and 1.309 Å respectively. The spin density
distribution of 1+ ion as depicted in Figure 4(c) is also similar to that of Cn● confirming that 1+ is a Cn●
complex of copper(I).
Electronic Spectra. The UV-vis-NIR absorption spectra of Cn●, 1 and PyCn● were recorded in CH2Cl2
and the spectra are shown in Figures 6(a) and 6(b). The spectrum of Cn● displays an absorption band at
530 nm. The absorption spectra of Cn● and Cn- forms are different. 1 containing Cn- as a ligand exhibits
a lower energy broader band at 720 nm and the characteristic bands at 470 and 450 nm. The absorption
feature of free Cn- ion was recorded by spectro-electrochemical measurement (Figure 7 (a)). Cn– reveals
absorption bands at 750, 500 and 480 nm.
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Figure 6. UV-vis-NIR absorption spectra of (a) Cn● (red) and 1 (green) and (b) PyCn● in CH2Cl2.
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Figure 7. Spectral changes during (a) Cn● → Cn-, (b) 1→ 1+ , (c) PyCn● → PyCn+ and (d) PyCn● → PyCn-
conversions recorded by spectroelectrochemical measurements in CH2Cl2 at 295 K.
The feature is similar to that of 1, only bands are red shifted by 30 nm. Thus the lower energy
absorption band of 1 at 720 is due to the Cn- ligand. In Cn● it is absent and during oxidation of 1 the
band gradually disappears (Figure 7 (b)). PyCn● exhibits a broader band at 500-550 nm and a weaker
NIR band at 800 nm. Both bands are assigned to
ꢀ
→ NB (singly occupied) charge transfer transitions
ꢀ
Ar
(Ar = aromatic and NB = non bonding). The changes of spectral features during PyCn● → PyCn+ and
PyCn● → PyCn- conversions were recorded by spectroelectrochemical measurements and are illustrated in
Py
Figures 7(c) and 7(d). During both conversions the absorption band of Cn● at 500-540 nm diminishes
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significantly. In PyCn- the NIR band at 800 nm is absent, while in PyCn+ it is hypsochromically shifted to
725 nm.
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Catalytic Activity. PyCn● has been established as a catalyst for the oxidative cleavage of benzil to
benzoic acid in methanol in air. Oxidative cleavage of benzil to benzoic acid is not common, generally
in presence of base benzil undergoes rearrangement to benzilic acid.14 However the reaction of benzil
(2.0 mmol) with PyCn● (0.07 mmol) in methanol in presence of triethylamine (0.03 mmol) and air at RT
for 48 h affords benzoic acid (3.44 mmol), corresponding to 86 % conversion (see, experimental section
in SI). The plausible path of the catalysis is depicted in Chart 3. Reaction of benzil with PyCn● produces
PyCn+ and a paramagnetic intermediate G that reacts with O2 molecules and generates intermediate H.
Chart 3. Catalytic Cycle of the Oxidative Cleavage of Benzil to Benzoic Acid in Presence of PyCn● and
Et3N in MeOH
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Reduction of H by another molecule of PyCn● generates a dioxetane intermediate I. I is not stable and
undergoes homolytic cleavage affording benzoic acid.19 Existence of intermediates (H) and (I) was
authenticated by ESI mass spectrometry of the crude reaction mixture after 48 h (see, Figure S9), where
no mass peak due to the unreacted benzil was detected. Formation of benzoic acid was confirmed by
single crystal X-ray crystallography.20 PyCn+ is an oxidizing agent (ECn+/Cn● = -0.34 V vs Fc+/Fc couple)
and the conversion of PyCn+ to PyCn● is achieved in MeOH which acts as a reducing agent (MeOH +
H2O = CO2 + 6H+ + 6e, E0 = 0.02 V vs SHE).21 The reaction of methanol with PyCn+ generated from a
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constant potential coulometric experiment was investigated by UV-Vis absorption spectra. It is observed
that PyCn+ reacts with methanol and the change of the absorption spectra of the mixture occurs with
several isosbestic points as depicted in Figure S10.
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Notably, the similar reaction of 2 2'-pyridil (0.5 m mol) with PyCn● (0.03 m mol) in methanol in
presence of triethylamine (0.02 mmol) and air at RT for 30 h affords picolinic acid in quantitative yields
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Py
(Figure S11). Thus, Cn● has been established as a catalyst for the oxidative cleavage of 1,2-diketones
to the corresponding acids.
Conclusion
A cascade route in isolating a new family of hetero-arene radicals as 1,2- benzodiazinyl radicals
(cinnolinyl radicals) is disclosed. Two structurally different cinnolinyl radicals, Cn● and PyCn● were
successfully isolated using 1,4-naphthoquinone as a precursor. Reaction of 1,4-naphthoquinoe with
hydrazine hydrate is (5e + 5H+) redox cascade and affords Cn●, while the same with 2-hydrazino
pyridine is a (7e + 7H+) oxidative cascade and affords PyCn●. The redox properties of Cn● and PyCn● are
significantly different. Cn● exhibits only cathodic wave due to Cn●/Cn- and Cn-/Cn●2- redox couple,
while PyCn● in addition to the cathodic wave displays a reversible anodic wave due to PyCn+/PyCn● redox
couple. Thus PyCn● is a reducing agent and different from hydrazyl radicals. Similar to phenalenyl
radical, PyCn● exhibits three redox states, PyCn+, PyCn● and PyCn-. PyCn● is a catalyst promoting oxidative
cleavage of benzil to benzoic acid in air. A Cn- complex of copper(I) containing PPh3 as coligands was
successfully isolated, opening up an opportunity to compare the bond parameters and spectral features
of Cn● and Cn-. Cn● and PyCn● are first paramagnetic neutral even alternate hetero-arenes and more
stable than the phenalenyl radical that has been considered as a functional material in devising
electronic devices and catalysts for several organic conversions. Thus isolation of Cn● and PyCn● is a
breakthrough in organic radical chemistry.
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Experimental Section
General Experimental Details
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Reagents or analytical grade materials were obtained from the commercial suppliers and used without
further purification. Spectroscopic grade solvents were used for spectroscopic and electrochemical
measurements. The C, H and N contents of the compounds were obtained from a Perkin-Elmer 2400
Series II elemental analyzer. Infrared spectra of the samples were measured from 4000 to 400 cm−1 with
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1
KBr pellets at room temperature on a Perkin-Elmer Spectrum RX 1 FT-IR spectrophotometer. H and
13C NMR spectra in CDCl3 solvent were recorded at 296 K on a Bruker Avance 500 MHz spectrometer.
ESI mass spectra were recorded on a Shimadzu LCMS 2020 mass spectrometer equipped with
electrospray ionization (ESI) ion source. Electronic absorption spectra in solution were obtained on a
Perkin-Elmer Lambda 750 spectrophotometer in the range 3300-175 nm. The X-band EPR spectra were
measured on a Magnettech GmbH MiniScope MS400 spectrometer (equipped with temperature
controller TC H03), where the microwave frequency was measured with an FC400 frequency counter.
The EPR spectra were simulated using Easy Spin software. The electro analytical instrument, BASi
Epsilon-EC for cyclic voltammetric experiments in CH3CN solutions containing 0.2 M
tetrabutylammonium hexafluorophosphate as supporting electrolyte was used. The BASi platinum
working electrode, platinum auxiliary electrode, Ag/AgCl reference electrode were used for the
measurements. The redox potential data are referenced vs. ferrocenium/ferrocene, Fc+/Fc, couple. BASi
SEC-C thin layer quartz glass spectroelectrochemical cell kit (light path length of 1 mm) with platinum
gauze working electrode and SEC-C platinum counter electrode were used for spectro-electrochemistry
measurements.
Single crystals of PyCn● and 1.½CH3OH were picked up with a nylon loop and were mounted on
Bruker AXS D8 QUEST ECO diffractometer equipped with a Mo-target rotating-anode X-ray source
and a graphite monochromator (Mo-Kα, λ = 0.71073 Å). Final cell constants were obtained from least-
squares fits of all measured reflections. Intensity data were corrected for absorption using intensities of
redundant reflections. The structures were readily solved by direct methods and subsequent difference
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Fourier techniques. The crystallographic data were listed in Table S1. The Siemens SHELXS-97
software package was used for solution, and SHELXL-97 was used for the refinement.22 All non-
hydrogen atoms were refined anisotropically. Hydrogen atoms were placed at the calculated positions
and refined as riding atoms with isotropic displacement parameters.
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All the calculations on PyCn● reported in this article were done with the Gaussian 09W23 program
package supported by Gauss View 4.1. The DFT24 calculations were performed at the level of Becke
three parameters hybrid functional with the non-local correlation functional of Lee-Yang-Parr
(B3LYP).25 Gas-phase geometry of PyCn● with doublet spin state was optimized using Pulay’s Direct
Inversion26 in the Iterative Subspace (DIIS), ‘tight’ convergent SCF procedure27 ignoring symmetry and
the optimized coordinates are given in Tables S2-S4. Valence double zeta with diffuse and polarization
functions, 6-31+G* as basis set28 was employed for all the atoms for all the calculations.
The DFT calculations on Cn●, CnH, 1 and 1+ were performed with the ORCA program package29 and
the optimized coordinates are given in Table S5-S8. The gas phase geometries of 1 and CnH were
optimized with singlet spin state, while Cn● in CH2Cl2 and 1+ in gas phase were optimized with doublet
spin state by hybrid PBE0 DFT method.30 In case of 1 the coordinates obtained from the single crystal
X-ray diffraction study were used as preliminary structures. For all calculations, the all-electron valence
double-zeta, def2-SVP31 basis set with “new” polarization function developed by Karlsruhe group was
used for N, P, O, C and H atoms. For Cu atom def2-TZVP,32 a valence triple-zeta basis set with new
polarization function was used. Resolution of Identity (RIJCOSX)33 approximation with def2/J auxiliary
basis set for Coulomb and HF exchange integral for HF and hybrid DFT methods were employed for
self-consistent field (SCF) gradient calculations.34 The geometry optimizations were carried out in
redundant internal coordinates without imposing symmetry constraints. The SCF calculations were
converged tightly (1 ×10-8 Eh in energy, 1 ×10-7 Eh in the density change and 1 ×10-7 in maximum
element of the DIIS error vector).
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Synthesis and Catalysis
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Benzo[g]naphtho[1,2-c]cinnolinyl-7,12,14-trione (Cn●) To a solution of 1,4-naphthoquinone (0.78 g,
5 mmol) in MeOH, hydrazine hydrate, 40% (0.312 g, 2.5 mmol NH2NH2.H2O) was added, and the
resulting mixture was stirred for 2 h at room temperature in air. A black solid of Cn● separated out,
which was filtered and dried in air. The obtained black mass was purified on an alumina column; the
product was eluted using n-hexane-CH2Cl2 (9:1) solvent mixture and the mass obtained after
evaporating solvent was used for further analyses. Yield: 0.56 g (~ 69 % with respect to 1,4-
naphthoquinone). Anal. Calcd (%) for C20H9N2O3: C, 73.84; H, 2.79; N, 8.61; Found: C, 73.52; H, 2.71;
N, 8.48. Mass spectrum (ESI): m/z, 325 for [Cn●, Figure S1]. IR/cm-1 (KBr): ν = 1680 (s), 1655 (s),
1578 (m), 1495 (s), 1435 (m), 1320 (m), 1210 (m), 1070 (m), 970 (s), 775 (m), 720 (m).
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6-(pyridin-2-yl)-6,7-dihydrobenzo[g]naphtho[2,3-c] (5,8,13,14 tetraone) cinnolinyl radical
(PyCn●): To a solution of 1,4-naphthoquinone (1.58 g, 10 mmol) in MeOH, 2-hydrazinopyridine (0.55 g,
5 mmol) was added, and the resulting mixture was stirred for 24 h at RT in air. A purple solid of PyCn●
separated out, which was filtered and dried in air. Single crystals for X-ray analysis were prepared by
the slow diffusion of n-hexane to the CH2Cl2 solution of PyCn● in a glass tube at 298 K. The crystals
were used for further analyses.Yield: 1.50 g (~ 71% with respect to 1,4-naphthoquinone). Anal. Calcd
(%) for C25H12N3O4: C, 71.77; H, 2.89; N, 10.04; Found: C, 71.50; H, 2.81; N, 9.93. Mass spectrum
(ESI): m/z, 420 for [PyCn●]+. IR/cm-1 (KBr): ν = 1685 (s), 1592 (s), 1505 (s), 1465 (m) 1430 (s), 1250
(m), 1170 (s), 1035 (m), 990 (s), 760 (m), 710 (m).
[Cu(Cn●)(PPh3)2] (1.½CH3OH): To a solution of Cn● (81 mg, 0.25 mmol) in CH3OH (40 mL) in a
100 mL round-bottom flask were added carefully [Cu(PPh3)3Cl] (220 mg, 0.25 mmol) followed by
triethylamine (1 drop, 0.50 mmol) and hydrazine hydrate (1 drop, 0.3 mmol). The solution turned green
and it was allowed to evaporate slowly in air. After 2-3 days, black crystals of 1 separated out, which
were collected upon filtration and dried in air. Yield: 130 mg (57% with respect to Cn●). Anal. Calcd for
C56H39N2O3P2Cu: C, 73.64; H, 4.30; N, 3.07. Found: C, 73.38; H, 4.16; N, 2.98. Mass spectrum (ESI):
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m/z 912 for [1]+. IR/cm-1 (KBr): ν 2930 (m), 1676 (s, CO), 1638 (s), 1565 (S), 1510 (m), 1290 (m),
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1235(s), 1090 (m), 815 (m), 725 (s), 685 (s), 522 (s).
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Catalytic Activity of Cn●. Oxidative Cleavage of Benzil to Benzoic Acid. To a solution of benzil
Py
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(420 mg, 2 mmol) in methanol (40 ml), PyCn● (30 mg, 0.07 mmol) was added and mixture was stirred
for 10 min at 298 K. The clear solution was allowed to evaporate slowly in air and after 48 h the residue
obtained after evaporation of the solvent was purified on a basic alumina column. The colorless eluent
obtained using pure CH2Cl2 as a solvent was collected and allowed to evaporate slowly in air. White
needles of benzoic acid grown from the solution were collected and used for further analysis. Yield 420
mg (86 % with respect to benzil).
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Oxidative Cleavage of 2 2'-Pyridil to Picolinic Acid. The reaction of 2 2'-pyridil (0.5 m mol) with
PyCn● (0.03 m mol) in methanol in presence of triethylamine (0.02 mmol) and air at RT for 30 h affords
picolinic acid in quantitative yields. In the mass spectrometry of the reaction mixture, a strong m/z peak
due to picolinic acid was detected and no m/z peak due to 2 2'-pyridil was observed.
ASSOCIATED CONTENT
Supporting Information
X-ray crystallographic data, ESI mass spectra, thermal ellipsoid plots, EPR spectra, frontier molecular
orbitals, change of UV-vis absorption spectra of PyCn+ in MeOH and gas phase optimized coordinates
with the computed total energies, CIF files. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Email: ghosh@pghosh.in; Phone: +91-33-2428-7347; Fax: +91-33-2477-3597
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The manuscript was written through contributions of all authors. All authors have given approval to the
final version of the manuscript.
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Funding Sources
The authors acknowledge the financial support received from DST (SR/S1/IC/0026/2012), New Delhi,
India.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
S. Mondal is thankful to SERB, New Delhi, India for SRF fellowship (EMR/2016/005222) and S. Bera
is thankful to SERB, New Delhi, India, for N-PDF fellowship (PDF/2016/001935).
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