Ligand Redox-Controlled Tandem Synthesis of Azines from Aromatic Alcohols and Hydrazine in Air: One-Pot Synthesis of Phthalazine

Article abstract of DOI:10.1021/acs.joc.8b00661

A controlled tandem synthetic route to azines from various alcohols and hydrazine hydrate by the use of a Ni(II) complex of 2,6-bis(phenylazo)pyridine as a catalyst is reported. In marked contrast to the previous report, the reaction is operative using an earth-abundant metal catalyst, milder reaction conditions, and aerobic conditions, which though are desirable but unprecedented in the literature. The catalytic reaction has a vast substrate scope including a single-step synthesis of phthalazine from 1,2-benzenedimethanol and hydrazine hydrate via intramolecular coupling. Mechanistic investigation suggests that the coordinated ligand redox controls the reaction by the use of a reversible azo (N=N)/ hydrazo (NH - NH) redox couple where the metal center is used primarily as a template.

Full text of DOI:10.1021/acs.joc.8b00661

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Article
Ligand Redox Controlled Tandem Synthesis of Azines from Aromatic
Alcohols and Hydrazine in Air: One-Pot Synthesis of Phthalazine
MOU CHAKRABORTY, Debabrata Sengupta, Tanushri Saha, and Sreebrata Goswami
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00661 • Publication Date (Web): 05 Jun 2018
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Ligand Redox Controlled Tandem Synthesis of Azines from Aromatic Alcohols and
Hydrazine in Air: One-Pot Synthesis of Phthalazine
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Mou Chakraborty,‡ Debabrata Sengupta,‡ Tanushri Saha and Sreebrata Goswami*
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, 2A & 2B
Raja S C Mullick Road, Jadavpur, Kolkata 700032, India
Email: icsg@iacs.res.in
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ABSTRACT:
A controlled tandem synthetic route to azines from various alcohols and hydrazine hydrate by the
use of a Ni(II) complex of 2,6ꢀbis(phenylazo)pyridine as a catalyst is reported. In marked
contrast to the previous report, the reaction is operative using earthꢀabundant metal catalyst,
milder reaction condition, and in aerobic conditions which though are desirable but
unprecedented in the literature. The catalytic reaction has vast substrate scope including a single
step synthesis of phthalazine from 1,2ꢀbenzenedimethanol and hydrazine hydrate via
intramolecular coupling. Mechanistic investigation suggests that the coordinated ligand redox
controls the reaction by the use of reversible azo (ꢀN=Nꢀ)/ hydrazo (ꢀNHꢀNHꢀ) redox couple
where the metal centre is used primarily as a template.
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INTRODUCTION:
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Azines (ꢀCH=NꢀN=CHꢀ) are important class of compounds having various industrial and
chemical applications due to their unique structural and stereochemical properties.1ꢀ4 This class
of compounds is now used as drug developing agents in pharmacological,5 and biological
industries,6 NLO materials,7 organic sensors,8,9 conductive polymers, image recording materials
etc.3 Apart from the industrial applications; azines are also widely used10ꢀ12 to synthesise
hydrazones and heterocyclic compounds. Heterocyclic azines13ꢀ15 have been widely used as
building blocks in supramolecular chemistry.
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Synthesis of azines commonly3 involves the coupling of hydrazines or hydrazones with the
respective carbonyl compounds. Besides, there are alternative routes,16 which are applicable only
for some specific substrates. Industrialists, however, have been using4,17 a multistep “peroxide
process” where ketones are coupled with ammonia in the presence of a sacrificial oxidant,
hydrogen peroxide. In this context, development of a singleꢀstep catalytic protocol for azine
synthesis directly from alcohol and hydrazine has been challenging. Recently, Milstein et al.
have reported18 a direct synthesis of azines from alcohols and hydrazine hydrate using a
rutheniumꢀPNP complex as a catalyst. Similar and recent work from the same group by the use
of a Mnꢀcatalyst19 has led to the formation of hydrazones instead of azines. Notably, the afore
noted azine synthesis protocol requires a long duration (>50h) and are carried out in deaerated
conditions using a precious metal Ruꢀcatalyst.
Herein, we wish to introduce a cascade synthetic route to azines in aerobic conditions, catalyzed
by a nickel(II) complex of a bis(azoaromatic) ligand. A wide variety of azines were synthesized
in high yields starting from the corresponding alcohols. Cascade reactions are worthy in the
synthetic organic chemistry because of higher atom economy and production of reduced
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chemical waste. Moreover, aerobic synthesis is not only users friendly, and is most desirable
option which produces no waste or water as sole by product.
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Scheme 1. Overview of the present work
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RESULTS AND DISCUSSION
Herein we have explored a new reaction protocol of using ligand redox for tandem synthesis of a
large variety of substituted azines by the coupling20ꢀ25 of hydrazine hydrate and alcohols strictly
in aerobic conditions. The catalyst is a NiIIꢀcomplex (1) of a recently reported26, 27 pincer ligand,
L (L = 2,6ꢀbis(phenylazo)pyridine) where the coordinated ligand controls the dehydrogenation
reaction, and the metal centre is used primarily as a template. The catalytic reaction has a huge
substrate scope, which includes aryl, polyaryl, heterocyclic moieties and operates in a relatively
milder conditions (Scheme 1) than the reported18 one. Using a similar protocol the synthesis of
phthalazine from 1,2ꢀbenzenedimethanol has also been achieved in oneꢀpot via the single step28
intramolecular coupling reaction. The synthesis of phthalazine and its derivatives commonly
involve multiple steps,17,28 and to the best of our knowledge,18 no catalytic method for direct
synthesis of phthalazine from 1,2ꢀbenzenedimethanol is reported so far.
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The complex, 1 is hexaꢀcoordinated where a NiII ion is coordinated by a tridentate ligand L, two
chloride ions and a labile water molecule (Figure 1). Recently, we have reported26 that this
complex brings about aerial alcohol dehydrogenation reaction29 effectively in the presence of a
reducing agent, zinc dust. This has prompted us to explore the oneꢀpot coupling30ꢀ33 reaction
between hydrazine hydrate and alcohols using hydrazine hydrate both as a reducing agent and
the reactant. We wish to note here that direct use of hydrazine in catalysis is challenging.18
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To explore the ideal reaction conditions, we have selected benzylalcohol as a model substrate. To
begin with, a mixture of equimolar solutions of benzylalcohol and hydrazine hydrate in the
presence 2 mol% 1, 5 mol% of potassium tertꢀbutoxide (tBuOK) and 1 g molecular sieves (3Å)
in toluene was heated at 80oC for 24h. The reaction resulted in the formation of 70%
benzaldehyde (3a) along with 25% of benzaldazine (entry 1, Table 1). Under identical
conditions, the reaction with the use of 2.1 equivalents of hydrazine hydrate led to the formation
of benzaldazine in 82% of isolated yield (entry 2ꢀ4, Table 1). Finally, in an optimum reaction
condition, a mixture of 1 mmol of benzylalcohol, 2 mol% of catalyst, 2.1 mmol of hydrazine
t
hydrate and 5 mol% of BuOK was heated at 80oC in toluene solvent in the presence of 1 g of
molecular sieves (3Å) for 24 h. The product was filtered through Whatman 41 filter paper to
remove the catalyst and molecular sieves. Finally, the crude mixture was purified by preparative
thin layer chromatographic technique using 1:10 ethyl acetate and hexane mixture as eluent.
Table 1 collects the optimization conditions of the reaction.
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Table 1. Optimizations table for the oneꢀpot coupling of hydrazine hydrate with benzylalcohol
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Entry
Time (h)
Temp.
(oC)
Base (mol
%)
Molecular
Sieves
Yield of
azine (%)
Yield of
Aldehyde
(%)
60d
48c
18c
6e
85d
42c
18c
82c
72c
10c
11c
9c
1a
2
24
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60
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80
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80
5
3 Å
25c, 32d
38c
70c
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12
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3 Å
3 Å
3 Å
3 Å
3 Å
3 Å
Nil
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5
82c, 94e
12c, 13d
46c
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Nil
Nil
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71c
8
Trace
15c
78c
76c
9
Nil
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12b
5
4 Å
5 Å
3 Å
5
5
79c
Catalytic condition: Catalyst 1 (2 mol%), benzylalcohol (1 mmol), hydrazine hydrate (2.1
mmol), 5 mL toluene. The reaction mixture was placed in a preheated oil bath with a condenser
under aerobic conditions. Here 1 mmol hydrazine hydrate was used. Here catalyst 2 was
employed instead of catalyst 1. cIsolated yield, dGCMS yield and eNMR yield.
a
b
Afterwards, we examined the scope of this protocol using various substituted benzylalcohols.
Substrates containing both electron donating (ꢀOMe, ꢀMe etc.) and electron withdrawing
(ꢀhalogens, ꢀCF3) groups work similarly in identical reaction conditions producing the desired
products in high isolated yields (>75%). For example, the reaction of 4ꢀ(methyl) and 4ꢀ
(methoxy) benzylalcohol with hydrazine hydrate in air afforded the corresponding azines (3b and
3g) in 85% and 78% of yield respectively in 24h. The reactions also occur freely with 3ꢀ
(methoxy) and 2ꢀ(methoxy benzylalcohols: the corresponding aldazines were isolated in 80%
and 82%, yields. Similarly, the reaction between 4ꢀ(trifluoromethyl)benzylalcohol with
hydrazine hydrate yielded 80% of the corresponding aldazines (3c). The reaction also proceeded
smoothly for the coupling of halogen substituted benzylalcohol (3d-f) where 76ꢀ82% yields were
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achieved. The latter compounds especially, bromoꢀ and iodoꢀ substituted aldazines are useful for
further functionalisation. To demonstrate the high scalability of the method, a gramꢀscale
reaction was also performed with the benzylalcohol (isolated product, 3a), where 80% yield was
achieved. The reaction protocol is not restricted only to the benzylalcohols but can be extended
further for polyaryl (pyrenaldazine, 3k) and heterocyclic (pyridinaldazine, 3j) substitutions.
Notably, the pyridinaldazines are useful building blocks for polymerisation,34 drug industries35
and supramolecular chemistry.36 However; these compounds are not otherwise achievable from
pyridylmethanols and hydrazine hydrate. The isolated azines along with their yields are collected
in Table 2.
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Table 2. [NiCl2L(H2O)] (1) catalysed oneꢀpot coupling of alcohols with hydrazine hydrate
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Encouraged by the above results, we subsequently have explored the intramolecular coupling
between 1,2ꢀbenzenedimethanol and hydrazine hydrate using an identical synthetic protocol. The
coupling does occur between the above two substrates in oneꢀpot producing Nꢀheterocyclic
phthalazine. The isolated yield of phthalazine (3l) was 52% with 10 mol% of catalytic loading
and heating the reaction mixture at 125oC for 24h; 18% of orthoꢀphthalaldehyde was also
isolated as a byproduct. It may be noted here that phthalazines belong to a special class of
nitrogen containing heterocycles, which are highly useful materials28 in medicinal as well as
material sciences (Scheme 2).
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Scheme 2. Single step catalytic phthalazine formation: Tandem coupling of 1,2ꢀ
benzenedimethanol with hydrazine hydrate
It is presumed that the first step of the reaction involves substitution of coordinated H2O in the
catalyst (1) by alcohol. To establish the substitution reaction, we stirred a methanolic solution of
the complex 1 at room temperature in the presence of 3Å molecular sieves for 4h. The colour of
the solution gradually became brownish green due to a substitution of H2O by CH3OH. A new
crystalline product was isolated from the reaction mixture and its single crystal Xꢀray diffraction
analysis has revealed that the isolated complex (2) is a methanol coordinated molecule with a
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similar structure to that of the aquaꢀcomplex, 1. An ORTEP representation of the isolated
complex 2 is shown in Figure 1. Spectral characterizations are described in experimental section
(Figure S13).
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Figure 1. Isolation of complex 2 from complex 1 and their ORTEP representations with 30%
probability ellipsoid. Solvent molecules were omitted for clarity.
Catalytic efficiencies of both 1 and 2 for the reference reaction are similar. For example, a
reaction between benzylalcohol and hydrazine hydrate under identical reaction conditions with
the use of complex 2 as catalyst yielded the product, 3a in 79% yield (entry 12, Table 1).
To elucidate the reaction further, we have followed a stoichiometric reaction between 1 and
hydrazine hydrate in benzylalcohol at room temperature. The green solution of 1 rapidly changes
to greenishꢀblue on the addition of hydrazine hydrate and the resultant mixture showed a single
line EPR spectrum signifying26 the formation of an azoꢀanion radical intermediate. The colour of
the mixture, on further stirring, became intense blue. The UVꢀvisible spectral feature of the
isolated blue intermediate is identical to that of the previously isolated complex, [Ni(H2L)Cl2]
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(Scheme 3, Figure S14). Taken all these together we conclude that the azine formation proceeds
via dehydrogenation37 of alcohols (Scheme 4). The reactions are controlled exclusively by ligand
redox and occur in the presence of air, which plays a crucial role26 in catalyst regeneration.
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Scheme 3. Single electron reduction of complex 1 in the presence of hydrazine hydrate
The catalytic reaction is also operative under baseꢀfree conditions; where 71% of the respective
azine (3a) was isolated (entry 7, Table 1). It thus appears that there is no major participation of
base in the catalytic cycle. But in the absence of molecular sieves and/or base (entries 8 and 9,
Table 1) the primary product is benzaldehyde (70%), and only trace amount of azine (3a) was
isolated from the mixture. This is as expected since it was reported previously26 that alcohol
dehydrogenation does take place freely even in the absence of a base. Thus the presence of
molecular sieves in azine formation directly from alcohol and hydrazine hydrate is vital, which
was also previously18 noted by Milstein.
To have a closer look at the possible interactions between the catalyst and hydrazine hydrate in
the cycle, three different reaction mixtures were subjected to spectroscopic analysis (Figure 2).
Firstly, we have performed an inꢀsitu IR study of the stoichiometric reaction mixture (A)
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consisted of the equimolar amount of catalyst 1 and benzylalcohol in the presence of two
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equivalent of hydrazine hydrate and molecular sieves (3Å).
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Figure 2. IRꢀspectral monitoring of NꢀH vibrational mode of hydrazine in the different reaction
mixtures
Notably, two sets of doublets characterising stretching modes of NꢀH (hydrazine) were observed
at 2883, 3076 and 2937, 3037 cmꢀ1. Presence of two types of hydrazine functions in the mixture
is as anticipated: (a) hydrazine function in coordinated H2L (formed during alcohol
dehydrogenation) and (b) hydrazine as the reagent for coupling reactions. To characterize the
above IRꢀstretching modes, we have performed IR spectral measurement on a similar reaction
mixture (B) where hydrazine hydrate was replaced by zinc dust as a reducing agent. Here only
one doublet stretching mode was observable at 2872 and 3076 cmꢀ1 which indicates that the other
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two IRꢀmodes in mixture arose due to the attachment of hydrazine hydrate to the central nickel
centre (NꢀH stretching mode of free hydrazine appears38 as a singlet at 3332 cmꢀ1). Furthermore,
a third reaction mixture (C), which is identical to that of (A), but contained D8ꢀbenzylalcohol in
place of H8ꢀbenzylalcohol was then examined using hydrazine hydrate as the reactant. Here the
NH stretching frequencies of coordinated hydrazines appeared at 2931 and 3029 cmꢀ1 while the
NꢀD stretching frequencies of the reduced ligand (D2L) appeared26 at 2105 and 2203cmꢀ1 (Figure
2). Thus it may be concluded that hydrazine is activated via coordination with the catalyst (NiIIꢀ
complex) to facilitate the coupling reaction. The proposed catalytic cycle is as follows.
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Scheme 4. Proposed catalytic cycle
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CONCLUSION:
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In conclusion, we have introduced the first example of ligand redoxꢀcontrolled direct synthesis of
azines by oneꢀpot coupling39ꢀ41 of aromatic alcohols and hydrazine hydrate in air using a Ni(II)ꢀ
complex of a bisꢀazoaromatic ligand as a catalyst. The working principle of our catalyst is
entirely different42ꢀ45 than that of commonly used catalysts. Notably, the catalytic reactions occur
in aerobic conditions which have been a challenge to both academia and industry. The reaction
encompasses high yield synthesis of a large variety of substrates including oneꢀpot synthesis of
industrially important phthalazine via intramolecular coupling of 1,2ꢀbenzenedimethanol and
hydrazine hydrate. Our future attempts are focused on the design of redox inactive main group
metal complexes of this and related azoꢀligands for dehydrogenative46ꢀ49 coupling reactions.
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EXPERIMENTAL SECTION:
Materials. [Ni(H2O)6]Cl2 was purchased from Merck, India. Alcohols were purchased from
either SigmaꢀAldrich or Alfa Aesar. All other reagents and chemicals were obtained from
commercial sources and were used without further purifications. Solvents were dried before use.
Physical Measurements. A PerkinElmer Lambda 950 spectrophotometer was used to record
UV−Vis spectra. Infrared spectra were obtained using a PerkinElmer 783 spectroꢀphotometer.
ESI mass spectra were recorded on a micromass QꢀTOF mass spectrometer (serial no. YA 263).
GCꢀMS analyses were performed using a Perkin Elmer CLARUS 680 instrument. NMR spectra
were recorded on a Bruker Avance 400 MHz or 500 MHz spectrometer, and SiMe4 was used as
the internal standard. A PerkinElmer 240C elemental analyzer was used to collect
microanalytical data (C, H, N). Xꢀband EPR spectra were recorded with a JEOL JESꢀFA200
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spectrometer. Roomꢀtemperature magnetic moment measurement for the complex 2 was
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performed with a Gouy balance (Sherwood Scientific, Cambridge, U.K).
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X-ray Crystallography. Crystallographic data for the compound 2 are collected in Table S1.
Suitable Xꢀray quality crystal of the complex 2 was obtained by the slow evaporation of a
dichloromethaneꢀmethanol solution (1:10) of the complex. The data were collected on a Bruker
SMART APEXꢀII diffractometer, equipped with graphiteꢀmonochromated Mo Kα radiation (λ =
0.71073 Å), and were corrected for Lorentz polarisation effects. Data for 2: a total of 10889
reflections were collected, of which 4177 were unique (Rint = 0.211), satisfying the I > 2σ(I)
criteria and were used in subsequent analysis. The structure was solved by employing the
SHELXSꢀ2014 program package50 and was refined by fullꢀmatrix leastꢀsquares based on F2
(SHELXLꢀ2014).51 All hydrogen atoms were added in calculated positions.
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Synthesis. The ligand L and the complex 1 were synthesised and purified as before.26,52
Synthesis of [NiIICl2L(CH3OH)], 2. A methanolic solution of 435 mg of the complex 1 was
stirred in the presence of 3Å molecular sieves for 4h. During this time the initial dark green
colour of the solution turned brownishꢀgreen. The crude mass, obtained by evaporation of the
solvent in vacuum, was purified by fractional crystallisation from methanol and ether solvent
mixture. Finally, the precipitate was recrystallised by slow evaporation of its dichloromethaneꢀ
methanol (1:10) solution. Its yield and characterisation data are as follows: Brownishꢀgreen
coloured solid. Yield: 367 mg (82%). Anal. Calcd. for C18H19Cl2N5NiO2: C, 46.30; H, 4.10; N,
15.00, Found C, 46.82; H, 3.91; N, 15.12%. Magnetic moment (ꢁ(300K)) = 2.43 B.M. UV−Vis
(CH3OH): λ [nm] (ε, M−1 cm−1) = 230 (41272), 275 (63027), 330 (44046): ν (N=N): 1404 cmꢀ1.
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General procedure for catalysis. The catalytic reactions were performed following a general
procedure. In a roundꢀbottom flask containing 1 mmol substrate in dry toluene (5ml) solvent was
mixed with 2ꢀ5 mol% of catalyst, 5 mol% of potassium tertꢀbutoxide (tBuOK), 2.1 mmol
hydrazine hydrate in the presence of 1g of molecular sieves (3Å). The flask was equipped with a
condenser, and the reaction mixture was heated at 80oC with constant stirring in a preheated oil
bath. The stirring was continued for 24ꢀ30 h depending upon a substrate. The resulting solution
was then filtered through Whatman 41 filter paper to remove the catalyst and the molecular
sieves. The filtrate was dried under reduced pressure and the organic product was extracted by
solvent extraction technique using dichloromethane/water solvent mixture. The dichloromethane
solution was collected, and the product was purified on a preparative Silica Gel GF 254 TLC
plate using hexane as eluent.
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(1E,2E)-1,2-dibenzylidenehydrazine (3a).18 The reaction was performed with a 108 mg (1mmol)
1
of benzylalcohol and 2 mol% of catalyst. Yellow solid (85 mg, 82% yield). H NMR (500 MHz,
CDCl3): δ = 7.45ꢀ7.46 (m, 6H), 7.83ꢀ7.85 (m, 4H), 8.66 (s, 2H). 13C NMR (125 MHz, CDCl3): δ
= 128.7, 128.9, 131.3, 134.3, 162.1.
(1E,2E)-1,2-bis(4-methylbenzylidene)hydrazine (3b).18 The reaction was performed with a 122
mg (1mmol) of 4ꢀmethylbenzylalcohol and 2 mol% of catalyst. Yellow solid (100 mg, 85%
1
yield). H NMR (400 MHz, CD3CN): δ = 2.38 (s, 6H), 7.31 (d, J = 8Hz, 4H), 7.75 (d, J = 8Hz,
4H), 8.59 (s, 2H). 13C NMR (125 MHz, CD3CN): δ = 20.6, 128.3, 129.5, 133.3, 139.5, 161.3.
(1E,2E)-1,2-bis(4-(trifluoromethyl)benzylidene)hydrazine (3c).53 The reaction was performed
with a 176mg (1mmol) of 4ꢀtrifluromethyl benzylalcohol and 2 mol% of catalyst. Yellow solid
(138 mg, 80% yield). ESIꢀMS for [3c+H]+ : calcd. for [C16H10F6N2+H]+, 345.0859; found,
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345.0851. H NMR (500 MHz, CDCl3): δ = 7.73 (d, J = 8.0, 4H), 7.98 (d, J = 8.0, 4H), 8.68 (s,
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2H) 13C NMR (125 MHz, CDCl3): δ = 125.9, 126.0, 129.0, 133.1, 137.4, 161.0.
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(1E,2E)-1,2-bis(4-chlorobenzylidene)hydrazine (3d).18 The reaction was performed with a 143
mg (1mmol) of 4ꢀchloro benzylalcohol and 2 mol% of catalyst. Yellow solid (113 mg, 82%
yield). 1H NMR (400 MHz, CDCl3): δ = 7.44 (d, J = 8.4, 4H), 7.79 (d, J = 8.4, 4H), 8.61 (s, 2H).
13C NMR (100 MHz, CDCl3): δ = 129.3, 129.9, 132.6, 137.5, 161.2.
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(1E,2E)-1,2-bis(4-bromobenzylidene)hydrazine (3e).54 The reaction was performed with a 187
mg (1mmol) of 4ꢀbromo benzylalcohol and 2 mol% of catalyst. Yellow solid (144 mg, 79%
1
yield). H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 8, 4H), 7.81 (d, J = 8.4, 4H), 8.65 (s, 2H).
13C NMR (100 MHz, CDCl3): δ = 124.9, 128.8, 130.1, 131.5, 161.1.
(1E,2E)-1,2-bis(4-iodobenzylidene)hydrazine (3f).55 The reaction was performed with a 234 mg
1
(1mmol) of 4ꢀiodo benzylalcohol and 2 mol% of catalyst. Yellow solid (175 mg, 76% yield). H
NMR (400 MHz, CDCl3): δ = 7.60 (d, J = 8.4, 4H), 7.72 (d, J = 8.8, 4H), 8.65 (s, 2H). 13C NMR
(100 MHz, CDCl3): δ = 126.0, 130.1, 132.3, 133.1, 161.3.
(1E,2E)-1,2-bis(4-methoxybenzylidene)hydrazine (3g).18 The reaction was performed with a 138
mg (1mmol) of 4ꢀmethoxy benzylalcohol and 2 mol% of catalyst. Yellow solid (104 mg, 78%
yield). 1H NMR (400 MHz, CDCl3): δ = 3.85 (s, 6H), 7.03 (d, J = 8.8Hz, 4H), 7.82 (4H, J = 8.8,
4H), 8.62 (s, 2H).
(1E,2E)-1,2-bis(2-methoxybenzylidene)hydrazine (3h).54 The reaction was performed with a 138
mg (1mmol) of 2ꢀmethoxy benzylalcohol and 2 mol% of catalyst. Yellow solid (110 mg, 82%
yield). 1H NMR (400 MHz, CDCl3):δ = 3.89 (s, 6H), 6.95 (d, J = 8.4Hz, 2H), 7.01 (m 2H), 7.41
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(m2H), 8.11 (d, J = 7.5Hz, 2H), 9.08 (s, 2H). C NMR (100 MHz, CDCl3): δ = 55.8, 111.4,
5
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121.0, 123.1, 127.5, 132.5, 157.6, 159.3.
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(1E,2E)-1,2-bis(3-methoxybenzylidene)hydrazine (3i).18 The reaction was performed with a 138
mg (1 mmol) of 3ꢀmethoxy benzylalcohol and 2 mol% of catalyst. Yellow solid (107 mg, 80%
yield). 1H NMR (500 MHz, CDCl3): δ = 3.88 (s, 6H), 7.02 (m, 2H), 7.35 (m, 4H), 7.44 (s, 2H ),
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8.62 (s, 2H). C NMR (125 MHz, CDCl3): δ = 55.5, 112.1, 118.1, 122.1, 129.9, 135.6, 160.1,
162.0.
(1E,2E)-1,2-bis(pyridin-2-ylmethylene)hydrazine (3j).3 The reaction was performed with a 109
mg (1mmol) of 2ꢀpyridine methanol and 5 mol% of catalyst. Yellow solid (73 mg, 70% yield).
1H NMR (500 MHz, CDCl3): δ =7.29ꢀ7.32 (m, 2H), 7.74 (t, J=7.5 2H), 8.08 (d, J=8, 2H), 8.63
13
(s, 2H), 8.67 (m, 2H). C NMR (125 MHz, CDCl3): δ = 122.5, 125.1, 136.6, 150.0, 152.9,
162.1.
(1E,2E)-1,2-bis(pyren-1-ylmethylene)hydrazine (3k).56 The reaction was performed with a 232
mg (1mmol) of 1ꢀpyrene methanol and 5 mol% of catalyst. Yellow solid (194 mg, 85% yield).
1H NMR (500 MHz, CDCl3): δ =8.09ꢀ8.31 (m, 14H), 8.49 (m, 2H), 9.05 (d, 2H), 9.56 (s, 2H).
Phthalazine (3l).28 The reaction was performed with a 138 mg (1mmol) of 1,2ꢀ
1
benzenedimethanol and 10 mol% of catalyst. Brownish yellow solid (68 mg, 52% yield). H
NMR (500 MHz, CDCl3): δ = 7.94ꢀ7.97 (m, 4H), 9.54 (s, 2H). 13C NMR (125 MHz, CDCl3): δ =
126.4, 126.7, 132.8, 151.2 .
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Controlled reactions:
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a. Reaction between complex 1 and hydrazine hydrate and H8-benzylalcohol. In a roundꢀ
bottom flask, 1 mmol H8ꢀbenzylalcohol in dry toluene (5ml) solvent was mixed with 1mmol of
catalyst, 2 mmol hydrazine hydrate, and 1g of molecular sieves (3Å). The flask was attached to a
schelnk line, and the reaction mixture was stirred at 320K under argon atmosphere. The stirring
was continued for 4h, and the solution was subjected to IR spectral analysis.
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b. Reaction between complex 1 and zinc and H8-benzylalcohol. In a roundꢀbottom flask, 1
mmol H8ꢀbenzylalcohol in dry toluene (5ml) solvent was mixed with 1mmol of catalyst, 1 mmol
of zinc dust, and 1g of molecular sieves (3Å). The flask was attached to a schelnk line, and the
reaction mixture was stirred at 320K under argon atmosphere. The stirring was continued for 4h,
and the solution was subjected to IR spectral analysis.
c. Reaction between complex 1 and hydrazine hydrate and D8-benzylalcohol. In a roundꢀ
bottom flask, 1 mmol D8ꢀbenzylalcohol in dry toluene (5ml) solvent was mixed with 1mmol of
catalyst, 2 mmol hydrazine hydrate, and 1g of molecular sieves (3Å). The flask was attached to a
schelnk line and the reaction mixture was stirred at 320K under argon atmosphere. The stirring
was continued for 4h and the solution was subjected to IR spectral analysis.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
CCDC number 1819227 contains the crystallographic data of the complex 2.
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Crystallographic details of complex 2 and copies of NMR spectra of the products are collected as
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supporting information (PDF).
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AUTHOR INFORMATION
Corresponding Author
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* (S.G.) Email: icsg@iacs.res.in
Author Contributions
‡These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The research was supported by the Science and Engineering Research Board, Department of
Science and Technology (DSTꢀSERB), India, funded projects SR/S2/JCBꢀ09/2011 and
EMR/2014/000520, respectively. MC is thankful to the DSTꢀSERB for DST Inspire programme
for her fellowship. TS is thankful to the Council of Scientific and Industrial Research for her
fellowship.
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Kuriyama, Y.; Nagata, N.; Yoshida, K.: Continuous manufacture of ketazine as an
intermediate for hydrazine hydrate. Mitsubishi Gas Chemical Company, Inc., Japan. US Patent
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US5986134A, 1997. Abstact. A process for continuously and stably synthesizing a ketazine from
hydrogen peroxide, ammonia and methyl ethyl ketone in the presence of a solution containing a
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comprises hydrolyzing the ketazine. By circulating unreacted ketone, accumulation of impurities
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Safari, J.; GandomiꢀRavandi, S.: Structure, synthesis and application of azines: a
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Schirmann, J. P.; Tellier, P.; Mathais, H.; Weiss, F.: Azines. Ugine Kuhlmann .
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Glaser, R.; Chen, G. S.; Anthamatten, M.; Barnes, C. L.: Comparative analysis of
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