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Phenyl boronic acid promoted efficient synthesis of perimidine derivatives under

mild condition

Vishvanath D. Patil, Ketan P. Patil, Nagesh R. Sutar* and Prathamesh V. Gidh*

Organic Chemistry Research Laboratory, Department of Chemistry, C. K. Thakur A.C.S. College New Panvel, Raigad,
Maharashtra, India
*Corresponding author’s E. mail: [email protected]

A R T I C L E I N F O A B S T R A C T

Article type: Various biologically important perimidines derivatives have been efficiently
Research article synthesized in excellent from Napthalene-1,8-diamine and various ketones in
Article history: presence of a catalytic amount of Phenyl boronic acid. This approach offers many
Received February 2016 advantages such as good product yield, short reaction time, easy isolation of
Accepted June 2016 products and mild reaction conditions.
July 2017 Issue
Keywords:
Ketone
Napthalene-1,8-diamine
Perimidines
Phenyl boronic acid
Reaction time
Mild reaction conditions
Bioactive compounds

© 2017 International Scientific Organization: All rights reserved.

Capsule Summary: 2,3-dihydo-1H-perimidines derivatives have been synthsized from Napthalene-1,8-diamine and various
ketones in presence of a catalytic amount of Phenyl boronic acid as lewis acid with excellent yields and mild reaction
conditions.

Cite This Article As: V. D. Patil, K. P. Patil, N. R. Sutar and P. V. Gidh. Phenyl boronic acid - promoted efficient synthesis of
perimidine derivatives under mild condition. Chemistry International 3(3) (2017) 195-201.

photochromic and thermochromic properties and thus used

INTRODUCTION in molecular switches, and photochemical memory
devices.(Komissarov et al., 1997; Norikane et al., 2009;
Nitrogen containing fused heterocyclic naphthalenes are Tamaoki et al., 2005) Synthesis of 2,3-dihydro-1H-perimidine
good candidates for biological, agricultural and medicinal (Paragamian et al., 1968) comprises reaction of naphthalene-
applications (Herbert et al., 1987; Denny et al., 2001; Dhanoa, 1,8-diamine with various carbonyl functionalities under
et al., 1999; Wasulko et al., 1966). Perimidine derivatives acidic condition.(Shaabani et al., 2008; Hendrickson et al.,
serve as ligand scaffolds (Chung et al., 2003; Hocek et al., 1987; Vanden et al., 1995; Ozeryanskii et al., 2001; Koh et al.,
2000), stoppers for supramolecules (Chiu et al., 2008), and 2002). The most frequent approach used for the preparation
couplers in hair colorants (Lagrange and Mignon, 2013). of dihydroperimidine derivatives is the reaction of
Their spiroperimidine derivatives exhibit reversible naphthalene-1,8-diamine with an aldehyde.
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Table 1: Comparison of the effect of solvent for the synthesis of 2,3-dihydo-1H-perimidines catalysed by phenyl
boronic acid
Entry Solvent Time (hrs.) Yielda (%)
1 CHCl3 2.3 58
2 CH2Cl2 2.15 52
3 CH3CN 2 62
4 C2H5OH 1.3 98
a Isolated Yield

Table 2: Investigation of catalytic effect of anhydr. Phenyl boronic acid on synthesis of 2,3-dihydo-1H-perimidines
Entry Anhyd. PhB(OH)2 Time Yielda
mmol Min %
1 0.01 45 52
2 0.05 40 58
3 0.1 30 98
4 0.2 29 98
a Isolated Yield

To the best of our knowledge, there are very few reports diamine with various ketones in presence of catalytic amount
available on the synthesis of dihydroperimidine derivatives of Phenyl boronic acid in Ethanol solvent (Scheme 1).
using ketone. In earlier reports, protonic acids are used as
catalyst to carry out above transformations with ketones MATERIAL AND METHODS
(Borovlev et al., 2008; Bazgir et al., 2010). Higher acidity of
Chemical and reagents
these catalysts results into the formation of various by-
products, which in turn lower the yield of desired product. All chemical and solvents were purchased from Merck and
The metal catalysts such as InCl3 (Bazgir et al., 2010), BiCl3 sigma Aldrich and used without further purification. The
(Yoon et al., 1991), Zn(CH3COO)2·2H2O (Belmonte et al., reaction was monitored by TLC using 0.25 mm E-Merck
2010) RuCl3 ( Zhang et al., 2007) Yb(OTf)3 (Zhang et al., 2008) silica gel plates, which were visualized in Iodine Chamber.
and HBOB (Shankarling et al., 2012) emerged as good Melting points were taken in open capillaries. 1H NMR in
alternatives for these conventional protic acids. Though most d6on 300 MHz using TMS as an internal standard 13C NMR
of these reactions were carried out at ambient temperature, spectra was recorded on JOEL EXC-500 spectrometer in
issues such as high cost and commercial availability of CDCl3.
catalyst, and longer reaction time (0.5 to 32 h) limit their
General procedure for synthesis of 2,3-dihydo-1H-
applicability on commercial scale.
perimidines
Phenyl boronic acid have received considerable
attention as an efficient catalyst in synthesis (Zheng et
A mixture of naphthalene-1,8-diamine (1 mmol), ketone
al.2010; Frutos et al.2011; Tale et al.2006; Krokhin et
(1.2 mmol) and Phenyl boronic acid (0.1 mmol) 0.1 g was
al.2010; Sridhar et al.2005; Debache et al., 2006; Lopez-Ruiz
stirred in ethanol at 75oC . The reaction progress was
et al., 2011; Tibhe et al., 2012).Herein we describe the use of
monitored by Thin layer Chromatography. After the
Phenyl Boronic acid as a lewis acid catalyst for synthesis of
completion of the reaction, hot ethanol was added to the
2,3-dihydo-1H-perimidines derivatives. This transformation
mixture and the catalyst was filtered off. After drying it was
was performed by condensation reaction of naphthalene-1,8-
purified by recrystallization from hot ethanol, pure
R' R products were obtained. The compounds were
HN NH
characterized using spectroscopic techniques.
NH2 NH2
PhB(OH)2
O
RESULTS AND DISCUSSION
+ R R' C2H5OH, 750C
The optimum condition for the synthesis of 2,3-dihydo-1H-
perimidines derivatives was established by considering a
Scheme 1: Synthesis of 2,3-dihydo-1H-perimidines using reaction between naphthalene-1,8-diamine and ketone as
naphthalene-1,8-diamine and aliphatic ketones using model reaction. It was performed in the presence of Phenyl
Phenyl borornic acid. boronic acid as a catalyst using ethanol as a solvent (Scheme
1).
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Table 3: Synthesis of different perimidine derivatives using naphthalene-1,8-diamine and aliphatic ketones
Entry Ketonea Time Productb Yieldc (%) M. P. (0C)
(Min)

O 30 min HN NH

1 86 115-116
(1a)

O HN NH

2 30 min 87 94-95
(1b)

O
HN NH
30 min 90 85-86
3
(1c)

O
HN NH
4 30 min 92 110-111

(1d)

O
5
HN NH

1.15 h 98 136-138
(1e)

O Cl

6 1.45 h
HN NH
92 129-130
Cl

(1f)

O Br

7 1.45 h 91 126-128
HN NH

Br

(1g)

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Table 3: continue…
Entry Ketonea Time Productb Yieldc (%) M. P. (0C)
(Min)
F

8 2h HN NH
91 156-158

(1a)

NO2

9 1.15 h HN NH 90 193-194

(1b)

10 1.15 h 95 118-119

(1c)

11 2.15 h 96 179-180

(1d)

12 1h 86 191-192

(1e)

13 12 No reaction ----- ----

A proper solvent for the reaction was selected by 0.05 mmol. A satisfactory yield in short reaction time was
investigating the effect of different solvents on reaction time obtained with 0.1 mmol of catalyst. There was no appreciable
and yield of product for model reaction. We observed that the improvement in yield even if loading amount was increased
reaction time was long and yield of the corresponding to 0.2 mmol.
product was low when the reaction was performed in Thus, the most appropriate loading amount for
solvents of low polarity (Table 1, Entries 1 and 2). Even in anhydrous PhB(OH)2 as a catalyst was found to be 0.1 mmol
CH3CN the reaction time and yield were not satisfactory as per results summarized in Table 2.
(Table 1, Entry 3). The reaction gave maximum yield of To evaluate the scope and generality of this
product in short time period when it was performed in polar methodology, a number of aromatic and aliphatic ketones
solvent such as C2H5OH (Table1, Entry-4) were further subjected to reaction using catalytic amount of
The efficiency of Phenyl boronic acid as a catalyst Phenyl boronic acid. In general, with aliphatic ketones, the
was determined with respect to its amount to be loaded in reactions showed better product yields and higher rate than
reaction mixture. There was no improvement in yield with aromatic ketones (Table 3 entries 1-4). Aromatic ketones,
increment in loading amount of catalyst from 0.01 mmol to such as acetopheneone, the conjugating factor of the phenyl
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ring, played a key role in affecting the rate of reaction, and transformation was successfully studied for different range
the reaction requires a longer time than aliphatic ketones. of ketones. The advantages include low cost, ease of catalyst
Moreover, various aromatic ketones containing either handling, mild reaction conditions and reactions carried out
electron donating (Table 3 entries 6-8,10-12) or electron at room temperature with excellent yields.
withdrawing substituents (Table 3 entries 9) at different
position worked well under present reaction condition. In ACKNOWLEDGEMENTS
benzopheneone, perhaps because of the conjugation effect of
two phenyl rings and the steric hindrance, the reaction The authors acknowledged the partial support of this work
showed no reaction (Table 3 entries 13). This proved the by Prof. B.P. Bandgar , Ex. Vice Chancellor, University of
wide scope and generality of the present protocol. The
Solapur, India and Dr. G. A. Meshram, Associate Professor,
results are summarized in Table 3.
The categorization data of various (1H NMR, Department of Chemistry, University of Mumbai, India. The
Infrared and Mass spectroscopy) achieved for various authors are thankful to Dr. S. T. Gadade, Principal, C. K.
representative compounds are given below. Thakur College for providing laboratory and other facilities.

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