A novel catalyst-free mechanochemical protocol for the synthesis of 2,3-dihydro-1H-perimidines

Article abstract of DOI:10.1002/jhet.3880

A rapid, efficient, and green grinding assisted method for the synthesis of 2,3-dihydro-1H-perimidines has been developed. 1,8-Diaminonaphthalene and aldehydes were ground using mortar and pestle for 5 minutes affording the product in moderate to excellen

Full text of DOI:10.1002/jhet.3880

Received: 10 October 2019
DOI: 10.1002/jhet.3880
Revised: 7 December 2019
Accepted: 11 December 2019
C O M M U N I C A T I O N S
A novel catalyst-free mechanochemical protocol for the
synthesis of 2,3-dihydro-1H-perimidines
Nissy Ann Harry1 | Sankaran Radhika1 | Mohan Neetha1
Gopinathan Anilkumar1,2
|
1School of Chemical Sciences, Mahatma
Abstract
Gandhi University, Kottayam, Kerala,
India
A rapid, efficient, and green grinding assisted method for the synthesis of
2,3-dihydro-1H-perimidines has been developed. 1,8-Diaminonaphthalene and
aldehydes were ground using mortar and pestle for 5 minutes affording the
product in moderate to excellent yields. The methodology minimises the use of
conventional workup and column chromatographic techniques.
2Advanced Molecular Materials Research
Centre (AMMRC), Mahatma Gandhi
University, Kottayam, Kerala, India
Correspondence
Gopinathan Anilkumar, School of
Chemical Sciences, Mahatma Gandhi
University, Priyadarsini Hills, Kottayam,
Kerala, India 686560.
K E Y W O R D S
aldehyde, grinding, ketone, mechanochemistry, perimidine
Email: anilgi1@yahoo.com
Funding information
EVONIK Industries, Grant/Award
Number: ECRP 2016 dated 6.10.2016;
Kerala State Council for Science,
Technology and Environment, Grant/
Award Number: 341/2013/KSCSTE dated
15.03.2013; EVONIK Industries, Germany;
Department of Science and Technology
(DST-New Delhi) under the DST-PURSE
programme; KSCSTE
1 | INTRODUCTION
nitrogen atoms to naphthalene ring make it a
π-deficient as well as π-excessive system. They serve as
photochemical memory devices and molecular switches
due to their reversible thermochromic and photochro-
mic properties.[3] Perimidine derivatives are also uti-
lized in plasma display panels, organic solar cells, and
optical recording media.[4] Perimidines also function as
a source of carbine ligand[5] and as dye intermediates.[6]
The synthesis of perimidine involves the reaction of
carbonyl compounds like anhydrides, acid halides, or
carboxylic acids with 1,8-diaminonaphthalene.[7] Reac-
tion of 1,8-diaminonaphthalene with aldehydes and
ketones results in the formation of 2,3-dihydro-1H-
perimidines which can be converted to perimidines by
dehydrogenation.[8] The existing reports for its synthesis
involve the use of various catalysts like NaY-Zeolite,[9]
Cu(NO3)2.6H2O,[10] Zn(OAc)2.2H2O,8b HPA/NaY,[11] I2,[12]
Mechanochemistry, carried out by grinding or milling, is a
prominent strategy for rapid, clean, and environmentally
friendly organic synthesis. These stress-induced chemical
reactions avoid the use of bulk solvent and, in many cases,
occur more efficiently and more selectively than does its
solution counterpart.[1] The hallmarks of mechanochemi-
cal reactions are its energy and cost efficiency since it
avoids the use of conventional laboratory equipment such
as stirrers and heaters, which makes it one of the greenest
methods in organic synthesis.
Perimidines are fused nitrogen containing heterocy-
clic naphthalenes exhibiting a wide range of biological
and material properties. They are well known for its
antifungal, antimicrobial, antitumor, and anti-ulcer
properties.[2] Movements of electron density from
J Heterocycl Chem. 2020;1–7.
wileyonlinelibrary.com/journal/jhet
© 2020 Wiley Periodicals, Inc.
1

2
HARRY ET AL.
FePO4,[13] nano-CuY zeolite,[14] Fe3O4@β-CD-ZrO[15] etc.
in organic solvents yielding products in moderate to good
yields.[16]
yields (Scheme 2). Here, the electronic effects of aldehydes
have least influence in the yield of the product while the
steric effect has some impact on the yields. The ortho- sub-
stituted aldehydes gave lower yields compared with the
corresponding para- substituted ones. The reaction
proceeded well with heterocyclic aldehydes like
furan-2-carboxaldehyde, thiophene-2-carboxaldehyde, and
pyridine-2-carboxaldehyde to furnish the corresponding
Catalysts like Fe3O4/SiO2/(CH2)3N+Me3Br3,[17] nano-
γ-Al2O3/SbCl5,[18] SiO2 NPs[19] etc were employed in a
solvent-free reaction for the synthesis of 2,3-dihydro-1H-
perimidines.
Recently, we have developed a catalyst-free “on
water” method for the synthesis of 2,3-dihydro-1H-
perimidines at room temperature in 30-minute time.[20]
The rate enhancement under the reaction condition was
assumed to be due to the combined effects of hydrogen
bonding in water and the hydrophobic nature of reactants.
The latter effect brings the reactants closer and thereby
enhancing the reaction rate. In an effort to perform this
reaction in a greener fashion, we tried to synthesize
2,3-dihydro-1H-perimidines by grinding method. We pre-
sume that the closeness of the reactants and increased
molecular collisions during grinding may trigger the reac-
tion. Herein, we report a catalyst-free grinding assisted
method for the synthesis of 2,3-dihydro-1H-perimidines
that completes in 5-minute time.
R
NH2 NH2
O
HN
NH
Grinding
H
R
5 min, RT
2
1
3
Me
OMe
OMe
OMe
HN
NH
HN
NH
HN
NH
HN
NH
HN
NH
3d, 91%
3e, 93%
OMe
3c, 88%
3a, 97%
Me
3b, 95%
Me
OH
N
MeO
OMe
OCH3
OH
OH
2 | RESULTS AND DISCUSSION
HN
NH
HN
NH
HN
NH
HN
NH
HN
NH
We started the first reaction by the grinding of 1,8-diamino
naphthalene with benzaldehyde using a mortar and pestle,
which afforded 2-phenyl-2,3-dihydro-1H-perimidine in 97%
yield in 5-minute time (Scheme 1). The crude product
obtained was recrystallized in EtOH to obtain the pure prod-
uct. The structure of the product was confirmed by spectro-
scopic techniques such as NMR and HRMS. Since
quantitative conversion was observed unlike the existing
protocols, we decided to investigate the substrate scope of
this transformation.
A broad range of substrates such as various aldehydes
and ketones were reacted with 1,8-diaminonaphthalene,
which was the only commercial amino substrate available.
Ortho-, meta-, para-, di-, and tri-substituted aldehydes
could efficiently react with 1,8-diaminonaphthalene to
afford the corresponding products in moderate to excellent
3g, 90%
3h, 92%
3i, 81%
3j, 89%
3f, 88%
Cl
Cl
F
Cl
Cl
NO2
HN
NH
HN
NH
HN
NH
HN
NH
HN
NH
3o, 82%
3k, 60%
3l, 75%
3n, 93%
3m, 90%
NO2
NO2
HN
NH
HN
NH
HN
NH
HN
NH
HN
NH
HN
NH
3p, 90%
3r, 97%
3q, 94%
3s, 96%
3t, 79%a
S
O
N
HN
NH
HN
NH
HN
NH
HN
NH
HN
NH
H
O
NH2 NH2
HN
NH
Grinding
3w, 70%
3v, 92%
3y, 51%
3u, 71%
3x, 73%
5 minutes, RT
SCHEME 2 Substrate scope studies towards the synthesis of
2,3-dihydro 1H-perimidines
SCHEME 1 Reaction between 1,8-diaminonaphthalene and
benzaldehyde
Reaction conditions: 1 (0.5 mmol), 2 (0.5 mmol), 5 min, RT, a1
(0.5 mmol), 2 (0.25 mmol), 5 min, RT

HARRY ET AL.
3
R
R'
NH
proceeded efficiently in 5 minutes with moderate to excel-
lent yields of the products. The reaction showed good func-
tional group tolerance with a wide range of aldehydes. The
studies on the biological activities of the synthesized per-
imidines are now going on in our laboratories.
NH2 NH2
O
HN
Grinding
R'
R
10 min, RT
4
1
5
H3C
HN
CH3
NH
CH3
NH
3.1 | Experimental section
HN
NH
HN
3.1.1 | General procedure for the
synthesis of 2,3-dihydro-1H-perimidines
5c, nd
5a, nd
5b, nd
1,8-Diaminonaphthalene 1 (0.5 mmol) and aldehyde
2 (0.5 mmol) were ground well in a mortar using a pestle
SCHEME 3 Reaction of 1,8-diaminonaphthalene with
ketones; reaction conditions: 1 (0.5 mmol), 2 (0.5 mmol), 10 min,
RT, a1 (0.5 mmol), 2 (0.25 mmol), 5 min, RT nd: not detected
R
NH2 NH2
HN
NH
O
Grinding
5 min, RT
H
R
O
NH2 NH2
N
NH2
HN
NH
1
2
3
+H+
- H+
-H2O
for 5 minutes. In all the cases, the reactants initially
became a pasty mass on grinding and then changed to
fine powder for solid products and viscous liquid for liq-
uid products (Figure 1). After the complete consumption
of reactants (monitored by TLC), the reaction mixture
was dissolved in ethyl acetate, and the solvent was evapo-
rated in vacuo. The crude mixture was purified by recrys-
tallization from either DCM/hexane mixture or from
ethanol affording 3. Low yielding products (3k, 3l, 3 t,
3u, 3w, 3x, 3y) were purified using silica gel column
chromatography using hexane-ethyl acetate mixture to
furnish the products which were characterized using
techniques such as NMR, IR and HRMS and MS-MS.
SCHEME 4 Mechanism for the formation of 2,3-dihydro-1H-
perimidines
perimidines 3u, 3v, and 3w in excellent yields. The reaction
was found to be feasible with aliphatic aldehydes also,
which gave lower yields (3x, 3y) than the aromatic alde-
hydes. The reaction did not occur in the case of ketones as
the substrates (5a, 5b, 5c) (Scheme 3). This is attributable to
the high activation energy of the reaction for ketones, pre-
sumably due to the less electrophilic nature of the carbonyl
carbon as well as its steric hindrance.
The mechanism of the reaction involves the forma-
tion of an imine at one of the amino groups of
1,8-diaminonaphthalene eliminating a water molecule
followed by a nucleophilic attack by the other amino
group to the imine furnishing the product (Scheme 4).
The increased molecular collisions between the reactants
presumably increase the rate of the reaction. In all the
cases, no side products or imines were isolated indicating
that the imine formation is the fastest step.
3.2 | Supporting information
Spectral data (1H, 13C NMR) of compounds 3a to 3y and
19F NMR spectrum of 3k are available.
3.2.1 | Characterization of the products
2-Phenyl-2,3-dihydro-1H-perimidine14,20(C17H14N2)
(3a): White solid, m.p.: 104ꢀC to 106ꢀC, 119 mg (97%).1H
NMR (400 MHz, DMSO-d6): δ7.67 (d, J = 8 Hz, 2H), 7.48
to 7.42 (m, 3H), 7.21 (t, J = 8 Hz, 2H), 7.05 (d, J = 8 Hz,
2H), 6.82 (s, 2H), 6.59 (d, J = 4 Hz, 2H), 5.43 (s, 1H)
ppm;13C NMR (100 MHz, DMSO-d6): 143.12, 141.83,
134.46, 128.56, 128.27, 127.96, 126.91, 115.38, 112.55,
3 | CONCLUSIONS
Thus, we have developed a greener methodology for the
synthesis of 2,3-dihydro-1H-perimidines using traditional
grinding with a mortar and pestle. This catalyst-free reac-
tion between 1,8-diaminonaphthalene and aldehydes

4
HARRY ET AL.
FIGURE 1 Reaction between
o-nitrobenzaldehyde and
1,8-diaminonaphthalene
A: Before reaction, B: During
grinding, the reaction mixture
becomes a pasty mass, C: After the
reaction the pasty mass turns into
powder, D: Pure product after
recrystallization
104.43, 66.51 ppm; HRMS (QToF): m/z calculated for
C17H15N2 ([M + H]+) 247.1191, found: 247.1236.
2-(p-Tolyl)-2,3-dihydro-1H-perimidine20
J = 4 Hz, 1H), 6.93 (d, J = 8 Hz, 1H), 6.75 (s, 1H),6.50 (d,
J = 8 Hz, 2H), 5.34 (s, 1H), 3.76 (s, 3H) ppm; 13C NMR
(100 MHz, DMSO-d6): 159.69, 143.98, 143.33, 134.83,
129.79, 127.35, 120.43, 114.38, 113.70, 112.93, 104.83,
66.52, 55.56 ppm; MS-MS (ESI): m/z calculated for
C18H17N2O([M + H]+) 277, found: 277.
(C18H16N2) (3b): White solid, m.p.: 141ꢀC to 143ꢀC,
1
123 mg (95%). H NMR (400 MHz, DMSO-d6): δ 7.50 (d,
J = 8 Hz, 2H), 7.24 (d, J = 8 Hz, 2H), 7.16 (t, J = 8 Hz,
2H), 6.99 (d, J = 4 Hz, 2H), 6.71 (s, 2H), 6.51 (d, J = 8 Hz,
2H), 5.34 (s, 1H), 2.34 (s, 3H) ppm; 13C NMR (100 MHz,
DMSO-d6): 143.34, 139.07, 137.94, 134.61, 128.91, 127.99,
127.04, 115.42, 112.70, 104.51, 66.40, 21.00 ppm; HRMS
(QToF): m/z calculated for C18H17N2([M + H]+)
261.1347, found: 261.1397.
2-(4-Methoxyphenyl)-2,3-dihydro-1H-peri-
midine20 (C18H16N2O) (3e): White solid, m.p: 160ꢀC to
165ꢀC, 128 mg (93%).1H NMR (400 MHz, DMSO-d6):
δ7.54 (d, J = 8 Hz, 2H), 7.16 (t, J = 8 Hz, 2H), 6.99 (d,
J = 8 Hz, 4H), 6.68 (s, 2H), 6.51 (d, J = 8 Hz, 2H), 5.32 (s,
1H), 3.77 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6):
159.53, 143.26, 134.41, 133.78, 129.11, 126.82, 115.21,
113.56, 112.49, 104.29, 66.03, 55.20 ppm; HRMS (QToF):
m/z calculated for C18H17N2O([M + H]+) 277.1296,
found: 277.1338.
2-(2-Methoxyphenyl)-2,3-dihydro-1H-peri-
midine[21] (C18H16N2O) (3c): White solid, m.p: 124ꢀC to
127ꢀC, 121 mg (88%).1H NMR (400 MHz, DMSO-d6):
δ7.54 (d, J = 8 Hz, 1H), 7.33 (t, J = 8 Hz, 1H), 7.14 (t,
J = 8 Hz, 2H), 7.07 (d, J = 8 Hz, 1H), 6.95 to 6.98 (m,
3H), 6.50 to 6.51 (m, 4H), 5.72 (s, 1H), 3.84 (s, 3H) ppm;
13C NMR (100 MHz, DMSO-d6): 157.43, 143.61, 134.86,
129.82, 129.74, 128.36, 127.33, 120.75, 115.68, 112.71,
111.45, 104.82, 60.00, 56.04 ppm; MS-MS (ESI): m/z cal-
culated for C18H17N2O([M + H]+) 277, found: 277.
2-(3-Methoxyphenyl)-2,3-dihydro-1H-peri-
4-(2,3-Dihydro-1H-perimidin-2-yl)-N,N-
dimethylaniline20(C19H19N3) (3f): Brown solid, m.p:
140ꢀC to 142ꢀC, 127 mg (88%).1H NMR (400 MHz,
DMSO-d6): δ 7.44 (d, J = 8 Hz, 2H), 7.15(t, J = 8 Hz,
2 H), 6.98 (d, J = 8 Hz, 2H), 6.77 (d, J = 8 Hz, 2H), 6.61
(s, 2H), 6.50 (d, J = 8 Hz, 2H), 5.26 (s, 1H), 2.90 (s, 6H)
ppm; 13C NMR (100 MHz, DMSO-d6): 151.38, 144.04,
134.93, 129.57, 129.07, 127.78, 115.53, 112.99, 112.48,
104.66, 66.85, 40.76 ppm; HRMS (QToF): m/z calculated
for C19H20N3([M + H]+) 290.1613, found: 290.1656.
midine[21] (C18H16N2O) (3d): White solid, m.p: 138ꢀC
to 141ꢀC, 126 mg (91%).1H NMR (400 MHz, DMSO-d6):
δ7.32 (t, J = 8 Hz, 1H), 7.17 to 7.13 (m, 4H), 6.98 (d,

HARRY ET AL.
5
2-(2,3-Dihydro-1H-perimidin-2-yl)phenol
2-(2-Chlorophenyl)-2,3-dihydro-1H-peri-
(C17H14N2O) (3g): White solid, m.p.: 190ꢀC to 193ꢀC,
118 mg (90).1H NMR (400 MHz, DMSO-d6): δ9.71 (s,
1H), 7.47 (d, J = 4 Hz, 1H), 7.20 to 7.13 (m, 3H), 6.99 (d,
J = 8 Hz, 2H), 6.89 (d, J = 8 Hz, 2H), 6.83 (t,J = 8 Hz,
1H), 6.56 (s, 2H), 6.52 (d, J = 4 Hz, 2H), 5.66 (s, 1H) ppm;
13C NMR (100 MHz, DMSO-d6): 155.39143.23, 134.38,
129.09, 128.37, 127.08, 126.80, 118.88, 115.40, 115.34,
112.46, 104.55 ppm; HRMS (QToF): m/z calculated for
C17H13ClN2 ([M + H]+) 263.1140, found 263.1171.
midine14,20 (C17H13ClN2) (3l): Off-white solid, 117ꢀC to
119ꢀC, 105 mg (75%).1H NMR (400 MHz, DMSO-d6):
δ7.81 (t, J = 4 Hz, 1H), 7.52 (t, J = 4 Hz, 1H), 7.42 (t,
J = 4 Hz, 2H), 7.22 (t, J = 8 Hz, 2H), 7.07 (d, J = 8 Hz,
2H), 6.80 (s, 2H), 6.59 (d, J = 8 Hz, 2H), 5.82 (s, 1H) ppm;
13C NMR (100 MHz, DMSO-d6): 142.83, 138.49, 134.41,
132.71, 130.08, 129.84, 129.30, 127.48, 126.95, 115.71,
112.33, 104.69, 62.67 ppm; HRMS (QToF): m/z calculated
for C17H14ClN2 ([M + H]+) 282.0738, found: 282.0774.
2-(3-Chlorophenyl)-2,3-dihydro-1H-peri-
3-(2,3-Dihydro-1H-perimidin-2-yl)phenol
(C17H14N2O) (3h): White solid, m.p.: 185ꢀC to 188ꢀC,
120 mg (92%).1H NMR (400 MHz, DMSO-d6): δ9.51 (s,
1H), 7.20 (t, J = 8 Hz, 1H), 7.14 (t, J = 8 Hz, 2H), 7.00 to
6.95 (m, 4H), 6.77 (d, J = 8 Hz, 1H), 6.72 (s, 1H), 6.48 (d,
J = 8 Hz, 2H), 5.25 (s, 1H) ppm; 13C NMR (100 MHz,
DMSO-d6): 157.37143.23, 143.10, 134.41, 129.18, 126.88,
118.53, 115.42, 115.17, 114.64, 112.41104.26, 66.35 ppm.
HRMS (QToF): m/z calculated for C17H13ClN2 ([M
+ H]+) 263.1140, found 263.1148.
midine14,20 (C17H13ClN2) (3m): Colourless liquid,
126 mg (90%).1H NMR (400 MHz, DMSO-d6): δ 7.68 (s,
1H), 7.55 (t, J = 4 Hz, 1H), 7.43 (d, J = 4 Hz, 2H), 7.16 (t,
J = 8 Hz, 2H), 6.99 (d, J = 8 Hz, 2H), 6.88 (s, 2H), 6.50 (d,
J = 8 Hz, 2H), 5.40 (s, 1H) ppm; 13C NMR (100 MHz,
DMSO-d6): 144.65, 142.52, 134.33, 132.87, 130.19, 128.26,
127.70, 126.93, 126.47, 115.45, 112.43, 104.47, 65.27 ppm;
HRMS (QToF): m/z calculated for C17H14ClN2 ([M
+ H]+) 282.0738, found: 282.0783.
4-(2,3-Dihydro-1H-perimidin-2-yl)-
2-(4-Chlorophenyl)-2,3-dihydro-1H-perimidine20
(C17H13ClN2) (3n):White solid, m.p.: 149ꢀC to 151ꢀC,
130 mg (93%).1H NMR (400 MHz, DMSO-d6): δ7.63 (d,
J = 8 Hz, 2H), 7.49(d, J = 8 Hz, 2H), 7.18 (t, J = 8 Hz,
2H), 7.01(d, J = 8 Hz, 2H), 6.81 (s, 2H), 6.53 (d, J = 8 Hz,
2H), 5.40 (s, 1H) ppm;13C NMR (100 MHz, DMSO-d6):
142.71, 140.92, 134.35, 132.94, 129.73, 128.18, 126.87,
115.43, 112.45, 104.45, 65.49 ppm; HRMS (QToF): m/z
calculated for C17H14ClN2 ([M + H]+) 282.0738, found
282.0780.
2-methoxyphenol20 (C18H16N2O2) (3i): White solid,
141ꢀC to 143ꢀC, 118 mg (81%). 1H NMR (400 MHz,
DMSO-d6): δ 9.10 (s, 1H), 7.19(s, 1H), 7.15 (t, J = 8 Hz,
2H), 7.02 to 6.96 (m, 3H), 6.82 (d, J = 8 Hz, 1H), 6.64 (s,
2H), 6.49 (d, J = 4 Hz, 2H), 5.25 (s, 1H) 3.80 (s, 3H) ppm;
13C NMR (100 MHz, DMSO-d6): 147.47, 146.95, 143.42,
134.42, 132.40, 126.83, 120.51, 115.18, 114.88, 112.49,
111.81, 104.27, 66.50, 55.64 ppm; HRMS (QToF): m/z cal-
culated for C18H17N2O2([M + H]+) 293.1245 cm−1
found: 293.1294.
;
2-(2-Nitrophenyl)-2,3-dihydro-1H-perimidine11,20
(C17H13N3O2) (3o): Orange solid, m.p.: 161ꢀC to 163ꢀC,
119 mg (82%).1H NMR (400 MHz, DMSO-d6): δ8.05 (d,
J = 8 Hz, 1H), 7.92 (d, J = 8 Hz, 1H), 7.76 (t, J = 8 Hz,
1H), 7.61 (t, J = 8 Hz, 1H), 7.19 (t, J = 8 Hz, 2H), 7.04 (d,
J = 8 Hz, 2H), 6.83 (s, 2H), 6.53 (d, J = 8 Hz, 2H), 5.85 (s,
1H) ppm; 13C NMR (100 MHz, DMSO-d6): 148.93, 142.04,
136.45, 134.26, 133.56, 129.89, 129.55, 127.00, 124.11,
115.78, 112.06, 104.75, 60.94 ppm; HRMS (QToF): m/z
calculated for C17H14N3O2 ([M + H]+) 292.1041, found:
292.1091.
2-(3,4,5-Trimethoxyphenyl)-2,3-dihydro-1H-peri-
midine20 (C20H20N2O3) (3j): White solid, 183ꢀC to
185ꢀC, 149 mg (89%).1H NMR (400 MHz, DMSO-d6):
δ7.16 (t, J = 8 Hz, 2H), 6.99 (d, J = 8 Hz, 2H), 6.96 (s,2H),
6.74 (s, 2H), 6.48 (d, J = 8 Hz, 2H), 5.30 (s, 1H), 3.80 (s,
6H), 3.67 (s, 3H) ppm;13C NMR (100 MHz, DMSO-d6):
152.77, 143.11, 137.63, 137.13, 134.39, 126.85, 115.33,
112.48, 105.15, 104.37, 66.56, 60.03, 55.92 ppm. HRMS
(QToF): m/z calculated for C20H21N2O3 ([M + H]+)
337.1507, found: 337.1551.
2-(2-Chloro-6-fluorophenyl)-2,3-dihydro-1H-peri-
midine20 (C17H12ClFN2) (3k): Yellow solid, m.p.: 131ꢀC
to 133ꢀC, 89 mg (60%).1H NMR (400 MHz, DMSO-d6):
δ7.51 to 7.45 (m, 1H), 7.39 (d, J = 8 Hz, 1H), 7.30 (t,
J = 8 Hz, 1H), 7.19 (t, J = 8 Hz, 2H), 7.03 (d, J = 8 Hz,
2H), 6.90 (s, 1H), 6.48 (d, J = 8 Hz, 2H), 6.00 (s, 1H) ppm;
13C NMR (100 MHz, DMSO-d6): 163.93, 161.40 (d,
J = 250 Hz), 143.24, 134.97, 134.88, 131.68, 131.58,
127.28, 126.45, 126.42, 126.04, 125.91, 116.37, 116.15,
115.77, 112.41, 104.68, 62.05 ppm; 19F NMR (470 MHz,
DMSO-d6): δ −108.85; HRMS (QToF): m/z calculated for
C17H13ClN2 ([M + H]+) 282.0738, found 282.0783.
2-(3-Nitrophenyl)-2,3-dihydro-1H-perimidine
(C17H13N3O3)20 (3p): Orange solid, m.p.: 173ꢀC to
175ꢀC, 131 mg (90%).1H NMR (400 MHz, DMSO-d6):
δ8.44 (s, 1H), 8.24 (d, J = 8 Hz, 1H), 8.04 (d, J = 8 Hz,
1H), 7.71 (t, J = 8 Hz, 1H), 7.17 (t, J = 8 Hz, 2H), 7.0 (d,
J = 8 Hz, 4H), 6.52 (d, J = 8 Hz, 2H), 5.55 (s, 1H) ppm;
13C NMR (100 MHz, DMSO-d6): 147.70, 144.57, 142.22,
134.60, 134.31, 129.91, 126.97, 123.26, 122.57, 115.66,
112.44, 104.63, 64.83 ppm; HRMS (QToF): m/z calculated
for C17H14N3O ([M + H]+) 292.1041, found: 292.1091.
2-(4-Nitrophenyl)-2,3-dihydro-1H-peri-
midine14,20(C17H13N3O3) (3q): Orange solid, m.p.:

6
HARRY ET AL.
190ꢀC to 191ꢀC, 137 mg (94%).1H NMR (400 MHz,
DMSO-d6): δ8.28 to 8.25 (m, 2H), 7.86 to 7.82 (m, 2H),
7.16 (d, J = 8 Hz, 2H), 7.00-6.98 (m, 4H), 6.52 to 6.49 (m,
2H), 5.54 (s, 1H) ppm; 13C NMR (100 MHz, DMSO-d6):
149.85, 147.43, 142.10, 134.32, 129.08, 126.99, 123.44,
115.62, 112.40, 104.61, 64.93 ppm; HRMS (QToF): m/z
calculated for C17H14N3O ([M + H]+) 292.1041, found:
292.1091.
DMSO-d6): 146.90, 142.70, 134.76, 127.36 (3C), 126.55,
116.04, 113.07, 105.12, 62.47 ppm; HRMS (QToF): m/z
calculated for C15H13N2S ([M + H]+) 253.0755, found
253.0797.
2-(pyridin-2-yl)-2,3-dihydro-1H-perimidine10
(C16H13N3) (3w): White solid, m.p.: 96ꢀC to 99ꢀC. 86 mg
(70%).1H NMR (400 MHz, DMSO-d6): δ8.59 (d, J = 4 Hz,
1H), 7.82, (t, J = 8 Hz, 1H), 7.58 (d, J = 8 Hz, 1H), 7.36 (t,
J = 6 Hz, 1H), 7.16 (t, J = 8 Hz, 2H), 6.95 to 6.99 (m, 4H),
6.55 (d, J = 8 Hz, 2H) 5.43 (s, 1H) ppm; 13C NMR (100 MHz,
DMSO-d6): 161.28, 149.16, 142.52, 137.41, 134.74, 127.42,
123.82, 121.55, 115.80, 112.86105.03, 67.27 ppm; HRMS
(QToF): m/z calculated for MS-MS (ESI): m/z calculated for
C16H14N3 ([M + H]+) 247, found: 247
2-(Naphthalen-1-yl)-2,3-dihydro-1H-per-
imidine11,20(C21H16N2) (3r): Pink solid, m.p.: 124ꢀC to
125ꢀC, 143 mg (97%).1H NMR (400 MHz, DMSO-d6): δ
8.12 (s, 1H), 8.00 to 7.96 (m, 4H), 7.78 (d, J = 8 Hz, 1H),
7.56 to 7.54 (m, 1H), 7.18 (t, J = 8 Hz, 2H), 7.02 (d,
J = 8 Hz, 2H), 6.87 (s, 2H), 6.54 (d, J = 8 Hz, 2H), 5.56 (s,
1H) ppm;13C NMR (100 MHz, DMSO-d6): 143.53, 139.69,
134.89, 133.65, 133.12, 128.42, 128.35, 127.44, 127.37,
126.73, 126.26, 115.81, 112.96, 104.85, 67.05 ppm; HRMS
(QToF): m/z calculated for C21H17N2([M + H]+)
297.1347, found: 297.1392.
2-Isobutyl-2,3-dihydro-1H-perimidine
(C15H18N2)20 (3x): Colourless liquid, 82 mg (73%).1H
NMR (400 MHz, DMSO-d6): δ7.14 (t, J = 8 Hz, 2H), 6.96
(d, J = 8 Hz, 2H), 6.50 (d, J = 8 Hz, 2H), 6.30 (s, 2H), 4.42
(t, J = 8 Hz, 1H), 2.07 to 2.00 (m, 1H), 1.57 (t, J = 8 Hz,
2H), 0.97 (d, J = 8 Hz, 6H); 13C NMR (100 MHz, DMSO-
d6): 143.60, 134.98, 127.24, 115.46, 113.29, 104.70, 62.40,
44.84, 23.46, 22.29 ppm. HRMS (QToF): m/z calculated
for C15H19N2 ([M + H]+) 227.1504, found 227.1549.
2-Ethyl-2,3-dihydro-1H-perimidine20 (C13H14N2)
(3y): Brown liquid, 51 mg (51%).1H NMR (400 MHz,
DMSO-d6): δ7.13 (t, J = 8 Hz, 2H), 6.93 (d, J = 8 Hz, 2H),
6.46 (d, J = 8 Hz, 2H), 6.33 (s, 2H), 4.30 (t, J = 4 Hz, 1H),
1.73 to 1.69 (m, 2H), 1.05 (t, J = 4 Hz, 3H) ppm; 13C
NMR (100 MHz, DMSO-d6): 143.73, 134.97, 127.27,
115.34, 113.07, 104.49, 65.13, 28.40, 8.86 ppm; HRMS
(QToF): m/z calculated for C13H15N2 ([M + H]+)
199.1191, found 199.1236.
2-([1,10-Biphenyl]-4-yl)-2,3-dihydro-1H-peri-
midine20 (C23H18N2) (3s): White solid, m.p.: 160ꢀC to
163ꢀC, 156 mg (96%). 1H NMR (400 MHz, DMSO-d6):
δ7.71 to 7.67(m, 6H), 7.48 (t, J = 8 Hz, 2H), 7.39 (t,
J = 8 Hz, 1H), 7.18 (t, J = 8 Hz, 2H), 7.01 (d, J = 8 Hz,
2H), 6.85 (s, 2H), 6.55 (d, J = 8 Hz, 2H), 5.44 (s, 1H) ppm;
13C NMR (100 MHz, DMSO-d6): 142.94, 141.05, 140.39,
139.88, 134.38, 128.92, 128.43, 127.47, 126.84, 126.66,
126.50, 115.26, 112.48, 104.34, 65.98 ppm; HRMS (QToF):
m/z calculated for C23H19N2([M + H]+) 323.1504, found:
323.1557.
1,4-Bis(2,3-dihydro-1H-perimidin-2-yl)benzene20
(C28H22N4) (3t): White solid, 196ꢀC to 198ꢀC, 164 mg
(79%).1H NMR (400 MHz, DMSO-d6): δ 7.61 (s, 4H), 7.16
(t, J = 8 Hz, 4H), 6.98 (d, J = 8 Hz, 4H), 6.83 (s, 4H), 6.52
(d, J = 8 Hz, 4H), 5.42 (s, 2H) ppm; 13C NMR (100 MHz,
DMSO-d6): 142.69, 142.33, 134.36, 127.42, 126.89, 115.20,
112.54, 104.40, 65.49 ppm; HRMS (QToF): m/z calculated
for C28H23N4 ([M + H]+) 415.1878, found: 415.1909.
2-(Furan-2-yl)-2,3-dihydro-1H-perimidine
ACKNOWLEDGMENTS
N.A.H. thanks the Council of Scientific and Industrial
Research (CSIR, India) for a junior research fellowship.
S.R. and M.N. thank the Kerala State Council for Science,
Technology, and Environment (KSCSTE), Trivandrum for
junior research fellowships. G.A. thanks the KSCSTE for a
research grant (Order no. 341/2013/KSCSTE dated March
15, 2013). We greatly acknowledge the support from the
Department of Science and Technology (DST-New Delhi)
under the DST-PURSE programme. The authors are also
thankful to EVONIK Industries, Germany for financial
support (ECRP 2016 dated 6.10.2016). We thank the Insti-
tute for Intensive Research in Basic Sciences (IIRBS) of the
Mahatma Gandhi University for NMR facility.
(C15H12N2O)20 (3u): Brown liquid, 83 mg (71%).1H NMR
(400 MHz, DMSO-d6): δ7.61 (bs, 1H), 7.18 (t, J = 8 Hz,
2H), 7.01 to 6.98 (m, 4H), 6.55 (d, J = 8 Hz, 2H), 6.40 to
6.38 (m, 1H), 6.31 (d, J = 4 Hz, 1H), 5.56 (s, 1H) ppm; 13C
NMR (100 MHz, DMSO-d6): 155.31, 142.21, 141.76,
134.32, 126.98, 115.44, 112.48, 110.35, 107.20, 104.59,
59.59 ppm; HRMS (QToF): m/z calculated for C15H13N2O
([M + H]+) 237.0983, found 237.1028.
2-(Thiophen-2-yl)-2,3-dihydro-1H-per-
imidine20(C15H12N2S) (3v): White solid, m.p.: 105ꢀC to
107ꢀC. 116 mg (92%).1H NMR (400 MHz, DMSO-d6):
δ7.52 (d, J = 4 Hz, 1H), 7.28, (d, J = 4 Hz, 1H), 7.16 (t,
J = 8 Hz, 2H), 7.01(t, J = 4 Hz, 3H), 6.92 (s, 2H), 6.51 (d,
J = 8 Hz, 2H), 5.71 (s, 1H) ppm; 13C NMR (100 MHz,
ORCID
Gopinathan Anilkumar https://orcid.org/0000-0002-
7907-5616

HARRY ET AL.
7
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
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How to cite this article: Harry NA, Radhika S,
Neetha M, Anilkumar G. A novel catalyst-free
mechanochemical protocol for the synthesis of 2,3-
dihydro-1H-perimidines. J Heterocycl Chem. 2020;
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