A novel eco-friendly on-water protocol for the synthesis of 2,2-disubstituted 2,3-dihydro-1H-perimidines

Article abstract of DOI:10.1002/jhet.4146

An efficient green on-water protocol for the synthesis of 2,2-disubstituted 2,3-dihydro-1H-perimidines is demonstrated. The reaction used safer p-toluenesulfonic acid (PTSA) as a catalyst on water at 80°C, for 2 hours affording a novel method for the synt

Full text of DOI:10.1002/jhet.4146

COMMUNICATION
A novel eco-friendly on-water protocol for the synthesis of
2,2-disubstituted 2,3-dihydro-1H-perimidines
Nissy Ann Harrya, Thomas Shilpaa, Sankuviruthiyil M. Ujwaldeva, Gopinathan Anilkumara,b,c
*
Water forms the nature’s common reaction medium. ‘‘On
water” reactions happens in water like an emulsion and show
unexpected reaction rate acceleration in comparison to other
organic solvents. The rate enhancement can be assigned to the
hydrogen bonding of water with the substrates and also due to
closeness of reactants due to hydrophobic effect.12 With our
previous experience in the on-water chemistry,13 we chose water
as the reaction medium for 2,2-disubstituted 2,3-dihydro-1H-
perimidine synthesis.
Abstract: An efficient green on-water protocol for the synthesis of
2,2-disubstituted 2,3-dihydro-1H-perimidines is demonstrated. The
reaction used safer PTSA as a catalyst on water at 80 oC, for 2
hours affording
a novel method for the synthesis of various
disubstituted perimidines in moderate to excellent yields.
Introduction
We chose p-toluenesulfonic acid (PTSA) to catalyze this
reaction. PTSA can act as an ecofriendly catalyst for a variety of
organic transformations, recyclable, cheap, non- oxidizing, non-
volatile, non-explosive, easy to handle and thermally robust.14
Perimidines are peri-naphtho-fused pyrimidine scaffolds, formed
by the ring closure reactions of 1,8-diaminonaphthalene. They
constitute a main class of natural and man-made compounds,
many of which shows useful agricultural, biological and
medicinal applications.1 Perimidines are used as NHC-ligands,2
couplers in hair colorants and stoppers for supramolecules.3 The
spiroperimidines serve as reversible thermochromic and
photochromic agents and are thus employed in photochemical
memory devices and molecular switches.4
Results and discussion
The optimisation reaction was carried out by the reaction of 1,8-
diaminonaphthalene with acetophenone. The reaction without
any catalyst in water at 80 oC, where only traces of product was
formed (Table 1, entry 1). The reaction was performed in ethanol
and t-BuOH solvents using iodine as the catalyst, affording the
products in lower yields of 52% and 67% respectively (Table 1,
entry 2, 3). The reaction performed in water resulted a higher
yield of 83% (Table 1, entry 4). Different compounds like I2,
acetic acid, FeCl3, Zn(OTf)2, Fe(OTf)3, PTSA etc. were used as
catalyst under the same reaction conditions (Table 1, entry 4-9).
Among that I2 and PTSA gave comparatively higher yields of 83
and 91% respectively. PTSA was selected as the optimised
catalyst for this reaction. When the reaction time was lowered to
2 hours yield remained almost the same (Table 1, entry 10). No
considerable increase in the yields was obtained when the
temperature was increased to 100 oC (Table 1, entry 16). A
lowering of yield to 74% occurred when the temperature was
decreased to 65 oC (Table 1, entry 15). Yields got decreased
when the amount of catalytic loading was varied to 5 mol% and
20 mol% (Table 1, entry 12, 13). A microwave reaction resulted
only average yield of 74% (Table 1, entry 14). Thus for 2,2-
disubstituted 2,3-dihydro-1H-perimidine synthesis we chose an
Perimidines are generally synthesized by the reaction of
1,8-diaminonaphthalene with various carbonyl compounds such
as aldehydes, ketones, carboxylic acids, anhydrides and acid
halides.5 To the best of our perception, there are only a few
reports regarding the synthesis of 2,2-disubstituted 2,3-dihydro-
1H-perimidines using ketone and 1,8-diaminonaphthalene are
available. In certain reports, some acidic compounds6 were
employed as catalyst to conduct the above reactions with
ketones. Various by-products are formed due to higher acidity of
these catalysts, which in turn decrease the yield of the
perimidines obtained. Later, some modified heterogeneous
catalysts were also employed for its synthesis.7 Certain metal
11
catalysts such as BiCl3,8 InCl3,9 RuCl3,10 Yb(OTf)3 emerged as
good alternatives. Though some of these protocols were
executed at ambient temperature, problems like high price,
commercial availability and moisture sensitivity of many of these
metal catalysts, and prolonged reaction time restricts their
implementation on a commercial scale. Also use of organic
solvents reduced the greenness of the reaction. Therefore, a
non-toxic, cheap, and easily available catalyst and a green
o
on-water method using PTSA as the catalyst, at 80 C, 2 hours
solvent
for
2,2-disubstituted
2,3-dihydro-1H-perimidines
as the optimized reaction condition (Table 1, entry 10). With
these optimised reaction conditions we started exploring the
substrate scope studies.
synthesis is still in demand.
[a]
[b]
[c]
School of Chemical Sciences, Mahatma Gandhi University,
Priyadarsini Hills, Kottayam, Kerala, INDIA 686560; Email:
anilgi1@yahoo.com, anil@mgu.ac.in; Fax: +91-481-2731036
Advanced Molecular Materials Research Centre (AMMRC),
Mahatma Gandhi University, Priyadarsini Hills, Kottayam, Kerala,
INDIA
Institute for Integrated programmes and Research in Basic Sciences
(IIRBS), Mahatma Gandhi University, Priyadarsini Hills, Kottayam,
Kerala, INDIA
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which may lead to differences between this version and the Version of Record. Please
cite this article as doi: 10.1002/jhet.4146
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COMMUNICATION
corresponding products 3u and 3v and 3t respectively. The non-
reactivity in the case of 1,3-diketones and ethyl acetoacetate
can be attributed to its ability to exist in the enol form. A general
trend in the yields shows that electron-donating groups on
acetophenone gives higher yield compared to electron-
withdrawing groups. This may be due to enhanced protonation
by PTSA on the carbonyl oxygen of the acetophenones
containing electron-donating groups. Among the synthesized
compounds 3j and 3k are novel perimidines.
SI.
No
1
Catalyst
Solvent
Water
EtOH
Tempera
ture (oC)
80
Time
(h)
4
Yield
(%)a
-
traces
2
3
I2
I2
I2
80
80
4
4
4
4
4
4
4
4
2
1
2
2
52
67
t-BuOH
Water
Water
Water
Water
Water
Water
Water
Water
Water
Water
Water
Water
Water
4
80
83
5
Acetic
acid
80
traces
15
6
FeCl3
80
7
Zn(OTf)2
Fe(OTf)3
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
80
30
8
80
45
9
80
91
10
11
12
13
14
15
16
80
90
80
85
80
75b
72c
74
80
MW, 80
65
10
min
4
74
100
2
91
Table 1: Optimisation studies for the synthesis of 2,2-disubstituted 2,3-
dihydro-1H-perimidines; Reaction conditions: (1 mmol), (1.1 mmol),
1
2
catalyst (10 mol%); a: Isolated yields; b: PTSA (5 mol%), c: PTSA (20 mol%).
1,8-Diaminonaphthalene, the only commercially available amine
substrate, was made to react with different ketones (Scheme 1).
Attempts towards derivatization of 1,8-diaminonaphthalene by
nitration, sulphonation, and bromination did not end up with any
positive results. Various ortho-, meta- and para- substituted
acetophenone derivatives 2 containing electron-withdrawing,
electron-donating and electron-neutral groups reacted with 1,8-
diaminonaphthalene 1 furnishing the 2,3-dihydro-1H-perimidine
product 3 in moderate to excellent yields. The reaction went
smoothly with heterocyclic ketones to furnish perimidines 3m
and 3n. Aliphatic butane-2-one afforded the corresponding
perimidine 3p in good yield, whereas the ring strains in the
spiroperimidines 3q and 3r formed from cyclopentanone and
cyclohexanone respectively affected the yields. The reaction
was prone to steric effects, ortho-substituted acetophenone
derivatives gave lower yields in comparison to the para-
substituted ones, whereas sterically hindered benzophenone
could not furnish the product. The reaction was attempted with
1,2-diketone, which afforded the product 3o in low yield whereas
1,3-diketones and ethyl acetoacetate did not furnish the
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COMMUNICATION
Scheme 1: Substrate scope studies for the synthesis of 2,2-disubstituted 2,3-
dihydro-1H-perimidines. Reaction conditions:
1 (1 mmol), 2 (1.1 mmol),
catalyst (10 mol%), water( 3mL), 80 oC, 2 h; a: time 4 h
The proposed mechanism involves the reaction initiation with the
protonation of acetophenone by PTSA, which reacts with the
1,8-diaminonaphthalene under the influence of on-water effect
(Scheme 2). Imine formation and nucleophilic addition by amino
group proceed quickly as we could not isolate imine or any other
side products.
Sl.
No
Catalyst
Reaction Conditions Yield Ref.
(%)
1
2
3
4
5
6
RuCl3.3H2O
BiCl3
EtOH, 40 oC, 30 h
EtOH, RT, 8 h
80
80
81
83
94
83
10
8
Yb(OTf)3
HBOB
EtOH, RT, 24 h
EtOH, 80 oC, 3 h
EtOH, 80 oC, 2 h
Water, 90 oC, 2 h
11
6b
7a
7b
Amberlyst
Chitosan
hydrochloride
Squaric acid
7
Water, 80 oC, 1.5 h
89
6e
8
PTSA
Water, 80 oC, 2 h
99
This
work
Table 2: A comparison of the catalytic activity and reaction conditions for the
synthesis of 2-methyl-2-(p-tolyl)-2,3-dihydro-1H-perimidine.
Conclusion
In conclusion 2,2- disubstituted 2,3-dihydro-1H-perimidines
synthesis was accomplished through a novel green on water
protocol. The reaction uses PTSA as catalyst and proceeds
under mild reaction conditions. Differently substituted aromatic
and aliphatic ketones showed excellent reactivity with 1,8-
diaminonaphthalene. The limitations of our methodology
involves the inability in the synthesis of sterically hindered 2,2-
disubstituted perimidines like 3o and 1,3-disubstituted
perimidines like 3u, 3v. The spiroperimidines also met with
traces or lower yields (3q, 3r). The protocol developed can be
extended towards the synthesis of 2,2-disubstituted perimidine
based squaraine dyes that may show excellent fluorescence and
may find different applications. Due to the immense importance
of perimidines in catalysis, material science and biology this
novel green protocol will be worthwhile to industrialists and
chemists.
Scheme 2: Proposed mechanism for the synthesis of 2,2- disubstituted 2,3-
dihydro-1H-perimidines using on-water method, Steps a & b: Protonation of
acetophenone by PTSA, Step c: reaction of protonated ketone with 1,8-
diamino naphthalene under on-water effect.
Further, we compared the efficiency of the newly developed
protocol with the existing approaches towards 2,2-disubstituted
2,3-dihydro-1H-perimidine synthesis. In the synthesis of 2-
methyl-2-(p-tolyl)-2,3-dihydro-1H-perimidine
from
1,8-
diaminonaphthalene with 4-methyl acetophenone, our protocol
has provided the highest yield when compared to the other
methods using transition metal catalysts or heterogeneous
catalysts (Table 2). The use of inexpensive, less toxic, easily
available PTSA as a catalyst in green solvent (water) under mild
reaction conditions are added advantages of this work. Different
types of ketones reacted to form perimidines with moderate to
excellent yields under the developed reaction conditions.
Experimental methods
General method for the synthesis of 2,2-disubstituted 2,3-
dihydro-1H-perimidines:
To a sealed tube, 1,8-diaminonaphthalene 1 (158 mg, 1 mmol),
PTSA (19 mg, 10 mol%), ketone 2 (1.1 mmol) were added
through the mouth of the tube. Distilled water (3 mL) was added,
sealed tube was closed with a cap and the mixture was stirred at
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COMMUNICATION
80 oC for 2 hours. When the reactants are completely consumed
(monitored by TLC), the reaction mixture was extracted using
EtOAc (3 x15 ml) and was evaporated in vaccuo. The
purification of crude mixture was done by doing silica gel column
chromatography with hexane-EtOAc mixture as the eluent to
afford the product and was characterized using NMR, HRMS
and MSMS.
1.68 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6): 146.23,
142.63, 136.01, 134.80, 128.86, 127.47, 126.55, 115.04, 113.40,
104.40, 67.89, 31.68, 20.94 ppm; MS-MS (ESI): m/z calculated
for C19H18N2([M+H]+) is 275, found: 275.
2-Methyl-2-(m-tolyl)-2,3-dihydro-1H-perimidine (C19H18N2)7b
o
3f: White solid, m.p: 111-114 C, 258 mg (94%). Rf : 0.54, 10%
EtOAc/Hexane.1H NMR (400 MHz, DMSO-d6): δ 7.41-7.33 (m,
4H), 7.08 (t, J = 8 Hz, 3H), 6.91 (d, J = 8 Hz, 1H), 6.82 (d, J = 8
Hz, 2H), 6.49 (d, J = 8 Hz, 2H), 2.20 (s, 3H), 1.62 (s, 3H) ppm;
13C NMR (100 MHz, DMSO-d6): 149.28, 142.54, 137.17, 134.76,
128.16, 127.64, 127.49, 127.18, 123.73, 114.96, 113.24, 104.27,
67.85, 31.68, 21.75 ppm; MS-MS (ESI): m/z calculated for
C19H18N2([M+H]+) is 275, found: 275.
Characterization of the products:
2-Methyl-2-phenyl-2,3-dihydro-1H-perimidine (C18H16N2)10,11
3a: White solid, m.p: 136-138 oC, 234 mg (90%). Rf : 0.40, 10%
1
EtOAc/Hexane. H NMR (400 MHz, DMSO-d6): δ 7.60 (d, J = 8
2-(4-Methoxyphenyl)-2-methyl-2,3-dihydro-1H-perimidine10
Hz, 2H), 7.38 (s, 2H), 7.20 (t, J = 8 Hz, 2H), 7.09 (t, J = 8 Hz,
3H), 6.83 (d, J = 8 Hz, 2H), 6.51 (d, J = 8 Hz, 2H), 1.65 (s, 3H)
ppm; 13C NMR (100 MHz, DMSO-d6): 149.32, 142.58, 134.84,
128.37, 127.99, 127.06, 126.64, 115.17, 113.39, 104.46, 68.05,
31.74 ppm; MS-MS (ESI): m/z calculated for C18H16N2([M+H]+)
is 261, found: 261.
o
(C19H18N2O) 3g: White solid, m.p: 150-153 C, 264 mg (91%).
Rf : 0.23, 10% EtOAc/Hexane.1H NMR (400 MHz, DMSO-d6): δ
7.47 (d, J = 8 Hz, 2H), 7.27 (s, 2H), 7.07 (t, J = 6 Hz, 2H), 6.81
(d, J = 8 Hz, 2H), 6.74 (d, J = 8 Hz, 2H), 6.47 (d, J = 6 Hz, 2H),
3.62 (s, 3H), 1.61 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6):
158.31, 142.57, 140.97, 134.75, 127.72, 127.46, 114.98, 113.60,
113.32, 104.32, 64.64, 55.37, 31.70 ppm; MS-MS (ESI): m/z
calculated for C19H18N2O([M+H]+) is 291, found: 291.
2-(4-Chlorophenyl)-2-methyl-2,3-dihydro-1H-perimidine
(C18H15ClN2)10,11 3b: White solid, m.p: 103-105 oC, 229 mg
(78%) (261 mg, 89%, reaction time 4 h). Rf : 0.28, 10%
EtOAc/Hexane. 1H NMR (400 MHz, DMSO-d6): δ 7.97 (d, J = 8
Hz, 2H), 7.39 (s, 2H), 7.25 (d, J = 8 Hz, 2H), 7.08 (t, J = 8 Hz,
2H), 6.83 (d, J = 8 Hz, 2H), 6.48 (d, J = 8 Hz, 2H), 1.62 (s, 3H)
ppm; 13C NMR (100 MHz, DMSO-d6): 147.93, 141.74, 134.29,
131.25, 128.16, 127.81, 127.07, 114.85, 112.84, 104.03, 67.30,
30.89 ppm; MS-MS (ESI): m/z calculated for C18H15ClN2([M+H]+)
is 295, found: 295.
2-(2-Methoxyphenyl)-2-methyl-2,3-dihydro-1H-perimidine
o
(C19H18N2O)7b 3h: White solid, m.p:123-126 C, 258 mg (89%).
Rf : 0.25, 10% EtOAc/Hexane.1H NMR (400 MHz, DMSO-d6): δ
7.31 (d, J = 8 Hz, 1H), 7.10-7.07 (m, 3H), 6.96-6.93 (m, 3H),
6.84 (d, J = 8 Hz, 2H), 6.70 (t, J = 6 Hz, 1H), 6.50 (d, J = 6 Hz,
2H), 3.90 (s, 3H), 1.73 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-
d6): 157.70, 142.24, 134.65, 134.60, 128.73, 128.01, 127.53,
120.21, 115.28, 112.65, 112.57, 104.44, 68.12, 56.17, 29.03
ppm; MS-MS (ESI): m/z calculated for C19H18N2O([M+H]+) is 291,
found: 291.
2-(4-Bromophenyl)-2-methyl-2,3-dihydro-1H-perimidine
(C18H15BrN2)10 3c: White solid, m.p: 90-93 oC, 237 mg (70%)
(317 mg, 94% reaction time 4 h). Rf : 0.21, 10% EtOAc/Hexane.
1H NMR (400 MHz, DMSO-d6): δ 7.52 (d, J = 8 Hz, 2H), 7.38-
7.39 (m, 4H), 7.08 (t, J = 8 Hz, 2H), 6.83 (d, J = 8 Hz, 2H), 6.49
(d, J = 8 Hz, 2H), 1.62 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-
d6): 148.41, 141.74, 134.30, 130.73, 128.58, 127.06, 119.82,
114.87, 112.87, 104.06, 67.36, 30.84 ppm; MS-MS (ESI): m/z
calculated for C18H15BrN2([M+H]+) is 339, found: 339.
4-(2-Methyl-2,3-dihydro-1H-perimidin-2-yl)aniline (C18H17N3)
3i: Brown solid, m.p: 140-143 oC, 267 mg (97%). Rf : 0.50, 20%
EtOAc/Hexane.1H NMR (400 MHz, DMSO-d6): δ 7.27 (d, J = 8
Hz, 2H), 7.13-7.10 (m, 4H), 6.86 (d, J = 8 Hz, 2H), 6.50 (d, J = 8
Hz, 2H), 6.43 (d, J = 8 Hz, 2H), 4.85 (s, 2H), 1.64 (s, 3H) ppm;
13C NMR (100 MHz, DMSO-d6): 147.49, 142.83, 136.02, 134.81,
127.46, 127.20, 114.88, 113.76, 113.34, 104.30, 67.71, 31.65
ppm; MS-MS (ESI): m/z calculated for C18H17N3([M+H]+) is 276,
found: 276.
2-(4-Iodophenyl)-2-methyl-2,3-dihydro-1H-perimidine
o
(C18H15IN2)10 3d: White solid, m.p: 104-106 C, 347 mg (90%).
1
Rf : 0.25, 10% EtOAc/Hexane. H NMR (400 MHz, DMSO-d6): δ
2-(2,4-Dichlorophenyl)-2,3-dihydro-1H-perimidine
7.55 (d, J = 8 Hz, 2H), 7.38-7.36 (m, 4H), 7.08 (t, J = 8 Hz, 2H),
6.83 (d, J = 8 Hz, 2H), 6.47 (d, J = 8 Hz, 2H), 1.61 (s, 3H) ppm;
13C NMR (100 MHz, DMSO-d6): 149.32, 142.20, 137.02, 134.72,
129.19, 127.48, 115.26, 113.29, 104.45, 93.14, 67.84, 31.26
ppm; MS-MS (ESI): m/z calculated for C18H15IN2([M+H]+) is 387,
found: 387.
o
(C18H14Cl2N2) 3j: White solid, m.p: 151-153 C, 181 mg (58%).
1
Rf : 0.28, 10% EtOAc/Hexane. H NMR (500 MHz, DMSO-d6): δ
7.59 (d, J = 10 Hz, 1H), 7.44 (s, 1H), 7.31 (s, 2H), 7.24 (d, J = 10
Hz, 1H), 7.11 (t, J = 8 Hz, 2H), 6.87 (d, J = 10 Hz, 2H), 6.52 (d, J
= 10 Hz, 2H), 1.79 (s, 3H) ppm; 13C NMR (125 MHz, DMSO-d6):
143.33, 141.19, 134.67, 133.02, 132.82, 131.48, 131.06, 127.99,
127.09, 115.62, 113.02, 104.45, 68.52, 27.70 ppm; HRMS
(QToF): m/z calculated for C17H12Cl2N2([M+H]+) 329.0607,
found: 329.0627.
2-Methyl-2-(p-tolyl)-2,3-dihydro-1H-perimidine
(C19H18N2)10
3e: White solid, m.p: 118-121 oC, 271 mg (99%). Rf : 0.29, 10%
1
EtOAc/Hexane. H NMR (400 MHz, DMSO-d6): δ 7.52 (d, J = 8
Hz, 2H), 7.36 (s, 2H), 7.13 (t, J = 8 Hz, 2H), 7.03 (d, J = 8 Hz,
2H), 6.87 (d, J = 8 Hz, 2H), 6.55 (d, J = 8 Hz, 2H), 2.19 (s, 3H),
2-Methyl-2-(4-(methylsulfonyl)phenyl)-2,3-dihydro-1H-
perimidine (C19H18N2O2S) 3k: Off-white solid, 280 mg (83%).
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COMMUNICATION
1
Rf : 0.19, 30% EtOAc/Hexane. H NMR (400 MHz, DMSO-d6): δ
7.87 (d, J = 4 Hz, 2H), 7.79 (d, J = 8 Hz, 2H), 7.53 (s, 2H), 7.10
(t, J = 8 Hz, 2H), 6.85 (d, J = 8 Hz, 2H), 6.54 (d, J = 4 Hz, 2H),
3.11 (s, 3H), 1.67 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6):
155.23, 141.49, 139.22, 134.25, 127.10 (3C), 126.70, 114.95,
112.76, 104.09, 67.53, 30.78 ppm; HRMS (QToF): m/z
calculated for C19H18N2O2S is 339.1162, found: 339.1191
1'H, 3'H-Spiro[cyclohexane-1,2'-perimidine] (C16H18N2)6b 3r:
White solid, m.p: 97-100 oC, 67 mg (28%). Rf : 0.38, 10%
EtOAc/Hexane.1H NMR (500 MHz, DMSO-d6): δ 7.09 (t, J = 8
Hz, 2H), 6.84 (d, J = 8 Hz, 2H), 6.44 (d, J = 8 Hz, 2H), 6.30 (s,
2H), 1.59 (bs, 8H), 1.40 (s, 2H) ppm; 13C NMR (125 MHz,
DMSO-d6): 141.90, 134.68, 127.46, 114.74, 112.53, 104.57,
64.99, 36.87, 25.68, 21.57 ppm; MS-MS (ESI): m/z calculated
for C16H18N2([M+H]+) is 239, found: 239.
2-Methyl-2-(4-nitrophenyl)-2,3-dihydro-1H-perimidine
(C18H15N3O2)10,11 3l: Orange solid, m.p: 163-165 oC, 247 mg
(81%). Rf : 0.14, 10% EtOAc/Hexane.1H NMR (400 MHz,
DMSO-d6): δ 8.06 (d, J = 8 Hz, 2H), 7.82 (d, J = 8 Hz, 2H), 7.54
(s, 2H), 7.09 (t, J = 8 Hz, 2H), 6.84 (d, J = 8 Hz, 2H), 6.52 (d, J =
6 Hz, 2H), 1.66 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6):
157.33, 146.47, 141.45, 134.36, 127.68, 127.21, 123.24, 115.24,
112.87, 104.31, 67.70, 30.50 ppm; MS-MS (ESI): m/z
calculated for C18H15N3O2([M+H]+) is 306, found: 306.
Acknowledgments
NAH and SMU thank the Council of Scientific and Industrial
Research (CSIR), New Delhi-India and University Grants
Commission (UGC), New Delhi for research fellowships. GA
thanks the Kerala State Council for Science Technology and
Environment (KSCSTE), Trivandrum, India for a research grant
(Order No.341/2013/KSCSTE dated 15.03.2013). The authors
are also thankful to EVONIK Industries, Germany for financial
support (ECRP 2016 dated 6.10.2016).
2-Methyl-2-(pyridin-3-yl)-2,3-dihydro-1H-perimidine
o
(C17H15N3)10 3m: White solid, m.p:180-183 C, 204 mg (78%).
Rf : 0.25, 30% EtOAc/Hexane.1H NMR (500 MHz, DMSO-d6): δ
8.76 (s, 1H), 8.30-8.28 (m, 1H), 7.93-7.92 (m, 1H), 7.44 (s, 2H),
7.23 (dd, J1 = 5 Hz, J2 = 10 Hz, 1H), 7.09 (t, J = 10 Hz, 2H), 6.85
(d, J = 10 Hz, 2H), 6.51 (d, J = 7 Hz, 2H) 1.66 (s, 3H) ppm; 13C
NMR (125 MHz, DMSO-d6): 148.55, 148.16, 144.15, 142.05,
134.71, 134.41, 127.53, 123.40, 115.49, 113.24, 104.65, 66.98,
31.24 ppm; MS-MS (ESI): m/z calculated for C17H15N3([M+H]+)
is 262, found: 262.
Keywords: Perimidines, Ketone, 1,8-Diaminonaphthalene,
Water, p-Toluene sulphonic acid, Green Chemistry.
References
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2-Methyl-2-(thiophen-2-yl)-2,3-dihydro-1H-perimidine
(C16H14N2S)10 3n: Colorless viscous liquid 133 mg (50%). Rf :
0.38, 20% EtOAc/Hexane.1H NMR (400 MHz, DMSO-d6): δ
7.23-7.06 (m, 6H), 6.93-6.91 (m, 2H), 6.83-6.80 (m, 1H), 6.49 (d,
J = 8 Hz, 2H), 1.80 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6):
154.29, 141.37, 134.16, 127.00, 126.10 (2C), 124.20, 115.03,
112.33, 104.36, 65.86, 30.79 ppm; MS-MS (ESI): m/z
calculated for C16H14N2S([M+H]+) is 267, found: 267.
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Phenyl(2-phenyl-2,3-dihydro-1H-perimidin-2-yl)methanone
(C24H18N2O)7b 3o: Yellow solid, m.p:140-143 oC, 133 mg (88%).
Rf : 0.66, 20% EtOAc/Hexane. H NMR (500 MHz, DMSO-d6): δ
7.76 (d, J = 8 Hz, 2H), 7.62 (d, J = 10 Hz, 2H), 7.52-7.49 (m, 3H),
7.42 (t, J = 10 Hz, 2H), 7.38-7.34 (m, 3H), 7.12 (t, J = 8 Hz, 2H),
6.95 (d, J = 8 Hz, 2H), 6.58 (d, J = 8 Hz, 2H) ppm; 13C NMR (125
MHz, DMSO-d6): 199.69, 141.42, 140.97, 135.19, 134.44,
132.83, 130.15, 128.85 (2C), 128.57, 127.47, 127.36, 115.90,
112.25, 105.14, 76.45 ppm; MS-MS (ESI): m/z calculated for
C24H18N2O([M+H]+) is 351, found: 351.
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1
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2-Ethyl-2-methyl-2,3-dihydro-1H-perimidine (C14H16N2)6b 3p:
Colourless liquid, 157 mg (74%). Rf
:
0.29, 10%
EtOAc/Hexane.1H NMR (400 MHz, DMSO-d6): δ 7.09 (t, J = 8
Hz, 2H), 6.85 (d, J = 8 Hz, 2H), 6.37 (d, J = 8 Hz, 2H), 6.27 (s,
2H), 1.63 (q, J = 8 Hz, 2H), 1.29 (s, 3H), 0.90 (t, J = 8 Hz, 3H),
ppm; 13C NMR (125 MHz, DMSO-d6): 142.32, 134.73, 127.49,
114.51, 112.09, 104.18, 66.27, 33.16, 26.38, 8.56 ppm; MS-MS
(ESI): m/z calculated for C14H16N2([M+H]+) is 213, found: 213.
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A novel eco-friendly on-water
protocol for the synthesis of 2,2-
disubstituted 2,3-dihydro-1H-
perimidines

Greener protocol for 2,2
disubstituted 2,3-dihydro-
1H-perimidines
Nissy Ann Harry, Thomas Shilpa,
Sankuviruthiyil M. Ujwaldev, Gopinathan
Anilkumar*



22 examples
Moderate to excellent yields
Page No. – Page No.
Safe PTSA catalyst, water
as solvent
This article is protected by copyright. All rights reserved.