Synthesis and biological evaluation of 1-amino isochromans from 2-bromoethyl benzaldehyde and amines in acid medium

Article abstract of DOI:10.1016/j.bmcl.2017.11.020

We have developed a facile and efficient synthetic route to substituted isochromans for the first time by reacting 2-(2-bromoethyl)benzaldehyde with a variety of aryl, heteroaryl amines in AcOH. The reaction is catalyst/additive free and takes place at reflux conditions with short reaction time to furnish products in good to excellent yields. All the compounds have been characterized by spectral techniques such as IR, ¹H NMR and Mass etc. Synthesized compounds were evaluated for antimicrobial activity against specific bacterial like 1) Staphylococcus strains aureus 2) Bacillus subtilis 3) Escherichia coli 4) Pseudomonas aeruginosa. Compounds 3e, 3n, 3 m, 3 l, 3 k, 3j and 3b showed most potent in vitro activity against bacterial strains.

Full text of DOI:10.1016/j.bmcl.2017.11.020

Accepted Manuscript
Synthesis and biological evaluation of 1-amino isochromans from 2-bromoethyl
benzaldehyde and amines in acid medium
Narjis Fatima, B.V. Subba Reddy, Gowravaram Sabitha, J.S. Yadav, K.
Sudhakar, Chandra Shekar Putta
PII:
S0960-894X(17)31107-1
https://doi.org/10.1016/j.bmcl.2017.11.020
BMCL 25426
DOI:
Reference:
Bioorganic & Medicinal Chemistry Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
1 August 2017
13 October 2017
9 November 2017
Please cite this article as: Fatima, N., Subba Reddy, B.V., Sabitha, G., Yadav, J.S., Sudhakar, K., Putta, C.S.,
Synthesis and biological evaluation of 1-amino isochromans from 2-bromoethyl benzaldehyde and amines in acid
medium, Bioorganic & Medicinal Chemistry Letters (2017), doi: https://doi.org/10.1016/j.bmcl.2017.11.020
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Synthesis and biological evaluation of 1-amino isochromans from 2-bromoethyl
benzaldehyde and amines in acid medium
Narjis Fatima,a,* B. V. Subba Reddy,a Gowravaram Sabitha,a J. S. Yadav,a K. Sudhakarb and Chandra
Shekar Puttab
aCenter for Semiochemicals Natural Products Chemistry Division, CSIR-Indian
Institute of Chemical Technology, Hyderabad-500007, India and bOsmania
University, Hyderabad-500 607, India.
E-mail:dr.narjisiict@yahoo.com; Ph no: +91-40-27191630; Fax: +91-40-27160512
Abstract: We have developed a facile and efficient synthetic route to substituted
isochromans for the first time by reacting 2-(2-bromoethyl)benzaldehyde with a variety
of aryl, heteroaryl amines in AcOH. The reaction is catalyst/additive free and takes place
at reflux conditions with short reaction time to furnish products in good to excellent
1
yields. All the compounds have been characterized by spectral techniques such as IR, H
NMR and Mass etc. Synthesized compounds were evaluated for antimicrobial activity
against specific bacterial like 1) Staphylococcus strains aureus 2) Bacillus subtilis 3)
Echerichia coli 4) Pseudomonas aeruginosa. Compounds 3e, 3n, 3m, 3l, 3k, 3j and 3b
showed most potent in vitro activity against bacterial strains.
Keywords: Isochromans, Isoquinolinones, heteroaryl amines, C-N bond, metal free
conditions, acid medium, antimicrobial, in vitro activity.
Many known biologically active compounds contain heterocyclic core, which is
an indispensable element for bio-activity. Among all the aromatic heterocycles, the
chemistry of functionalized isochroman and isoquinolone continues to be of great interest
because of the industrial and biological importance of these class of compounds. The C-N
bond conversions have attracted much interest because nitrogen-containing functional
groups that are prevalent in many natural products and pharmaceuticals.1 Therefore, many
remarkable endeavours have been made to develop efficient and general methods for the
amination reactions.2
*Corresponding author. Phone: +91-40-27191629; Fax: +91-40-27160512
E-mail: dr.narjisiict@yahoo.com
1

Isochroman derivatives generally exhibit various pharmaceutical activities3 and
serve as interesting building blocks in synthetic chemistry.4 Chiral 1-substituted
isochromans constitute the core of many natural products such as cytosporone C−D5 and
synthetic sonepiprazole (U-101387) (Figure 1), a selective dopamine D4 receptor
antagonist.6 Isochroman-6-carboxamide, (S)-(-)-PNU-1092917 was found to be as a
highly selective 5-HT1D agonist for the treatment of migraine headache. Isochromane
moieties found in isochromans have shown in Figure 1.11
C-H Bond functionalization12a is one of the strategies used for the preparation of
1-substituted isochromans. However formation of substituted isochroman using
hypervalent iodine,12b metal catalysts,12c non-haeme iron mediated amidation,12d copper
as catalyst and N-halosuccinimide as oxidants,12e asymmetric catalysis,12f Oxa- Pictet-
Spengler reaction,12g the cyclisation of phenylseleno alcohols,12h the addition of ortho-
lithiated aryl oxiranes to enaminones,12i was studied so far.
The isoquinolone ring system is an interesting structural motif not only because of
its presence in several natural compounds, but also it is a useful building block in
medicinal and organic chemistry.13 Furthermore, its framework has been found to be a
useful chemical scaffold for the synthesis of more elaborate molecules with
2

pharmacological properties.14 Isoquinolone core is the common structural motif in
alkaloids15 in Figure 2
Synthesis of N-substituted 4-methylene-3,4-dihydro-1(2H)-isoquinolinones16
involves palladium-catalysed multicomponent processes utilising allenes, with both 2-
iodo esters and 2-iodo acyl chlorides. C-H functionalization reaction could be used for
the preparation of substituted N-aryl tetrahydroquinolines.17 They are accessible by
intramolecular functionalization of benzylic methylene adjacent to the ring nitrogen atom
in N-aryltetrahydroisoquinoline derivatives.18
Eventhough, substituted isochromans are known in the literature, there exists no
reports on the synthesis of isochroman-1-amine derivatives. Thus, we became interested
to meet this challenge. In connection with our group objective in developing new
synthetic strategies for diverse and complex polyheterocycles,19 herein we report a novel
strategy for the rapid access to substituted N-aryl, heteroaryl isochromans 3 and N-aryl,
heteroaryl tetrahydroisoquinolones 4 by using 2-(2-bromoethyl)benzaldehyde 1 as the
substrate and a variety of amines 2 (Scheme 1).
Scheme 1. Synthesis of amino-substituted isochroman
3

In this context, we observed in the literature that 2-(2-bromoethyl)benzaldehyde
was explored as a substrate in DCE to access only tetrahydroisoquinolines,20 and no
report exist on the formation of isochromans, either in the presence of external
nucleophiles or presence of other nucleophilic group in the amine compound.21 Further, it
was reported that the reaction of 2-(2-bromoethyl)benzaldehyde with aromatic amines
generate highly reactive iminium intermediate.
Br
NuH
(eq 1)
+
NH2
+
R
N
R
N
ref. 20
CHO
CHO
R
Nu
Nu
Br
90 oC
N
(eq 2)
DCE,
ref. 21
H2N
+
Nu
Scheme 2. Previous approaches using 2-(2-bromoethyl)benzaldehyde
This intermediate, if treated with external nucleophiles, gives rise to 1-substituted
N-aryltetrahydroisoquinolines20 as
products (eq 1), whereas, if 2-(2-
bromoethyl)benzaldehyde is treated with bisnucleophiles21 it forms fused
tetrahydroisoquinoline scaffolds as products in DCE at 90 oC (eq 2) (Scheme 2).
Initially, the reaction of 2-(2 bromoethyl)benzaldehyde 1 with N-(isochroman-1-
yl)-4-methoxybenzo[d]thiazol-2-amine 2 in AcOH at r.t for 1-24 h did not give any
product rather the starting materials were recovered (entry 1). Increasing the reaction
o
temperature to 40 C resulted in slight formation of the product after for 4 h (entry 2).
However, we observed the formation of two compounds, N-(isochroman-1-
yl)benzo[d]thiazol-2-amine 3a and 2-(benzo[d]thiazol-2-yl)-3,4-dihydroisoquinolin-
1(2H)-one 4a at 80 oC (entry 3) (Table 1). These two products were separated by column
chromatography to give 3a in 73% yield and 4a22 in 20%. The structure of the products
was established based on 1H NMR, Mass spectral data. To the best of our knowledge, this
is the first report on the reaction of 2-(2 bromoethyl)benzaldehyde 1 with heterocyclic
4

amine 2 without use of any external nucleophiles to give isochroman-1-amine derivative
as a major product.
Table 1. Optimization conditions for the synthesis of 1-sustituted isochromana
O
Br
AcOH
S
N
N
S
H2N
+
HN
+
S
CHO
O
N
N
OMe
1
MeO
2a
3a
4a
MeO
Entry
Amines
Temp(oC)/Time Solvent
Yieldb
1
2
3
4-methoxybenzo[d]thiazol-2-amine
4-methoxybenzo[d]thiazol-2-amine
4-methoxybenzo[d]thiazol-2-amine
r.t/1-24 h
40 oC/4 h
80 oC/4 h
AcOH
AcOH
AcOH
c
traces
73% 3b, 20% 10b
a Reaction conditions: 1 (1 eq) and 2b (1.2 eq). b Isolated yields after column chromatography, c no product
formation
With the optimized reaction conditions, synthetic potential of 2-(2-
bromoethyl)benzaldehyde 1 was tested using different substituted 2-aminobenzothiazoles
to give the products (3a-3h and 4a-4h) in varied yields (Scheme 3). In all the cases,
isochromans were formed as major and tetrahydroisoquinolones as minor products. The
results are shown in Table 2.
O
R1
Br
AcOH
S
N
N
S
H2N
+
HN
+
S
80 oC, 4 h
CHO
R1
O
N
R1
N
R
R
1
2a-g
3a-g
4a-g
R
minor
major
Scheme 3. Standard reaction conditions for product formation.
5

Table 2. Substrate scope for the formation 1-substituted isochroman derivatives
O
O
S
O
S
O
S
HN
N
HN
HN
N
N
OMe
HN
N
S
F
CF3
Br
3c (from 2c), 70%
3d (from 2d), 71%
3b (from 2b), 75%
3a (from 2a), 73%
O
S
O
O
OMe
N
N
HN
HN
N
N
HN
N
O
S
S
S
OEt
Me
3f
2f
(from ), 72%
4a
2a
(from ), 20%
3e (from 2e), 77%
3g (from 2g), 71%
N
N
N
N
N
N
N
N
O
S
O
S
S
O
O
S
CF3
Br
OEt
4e (from 2e), 21%
F
4b
2b
(from ), 22%
4c (from 2c), 18%
4d (from 2d), 23%
N
N
N
N
O
S
S
O
Me
4g
2g
(from ), 18%
4f
2f
(from ), 15%
On the basis of the arrived results, we investigated the substrate scope for the
transformation to other coupling amines such as 2-aminothiazoles 2h-2j (Table 3) and 2-
aminopyridines 2k-2m (Table 4) in the present protocol, which afforded a variety of
functionalized isochromans 3h-3j as major products along with N-protected
tetrahydroisoquinolin-1-ones 4h, 4k as minor products (except for few compounds such
as 4i, 4j, 4l) in synthetically viable yields .
6

Table 3. Substrate scope for the formation 1-substituted isochroman derivatives
Table 4. Substrate scope for the formation 1-substituted isochroman derivatives
On our way to synthesize more compounds we found the substituted pyridine with
alkyl group at the ortho position to NH2-group would result in violation of the desired
product rather we noticed an exclusive formation of 3m, when amino compound 2m was
treated with 2-(2-bromoethyl)benzaldehyde 1 it may be due to potentially disfavourable
steric interactions present between the methyl–substituent and the hydroxyl group of the
hemiaminal leading to the formation of aldehyde compound 3m (Scheme 4).23
7

Scheme 4. Formation of N-alkylated product
In order to establish the structure of isochroman derivative formed, methylation
reaction was performed with iodomethane in THF. The NMR spectrum of the
compound 11a showed the CH3 proton for the N-Me moiety at 2.99 (s, 3H) ppm and
mass at m/z 327(M+H). (Scheme 5). With the data of alkylated compound (11a), we
could confirm the structure once again.
Scheme 5. Confirmation by derivatisation of isochroman product
A plausible mechanism for the acetic acid promoted metal-free C-N bond-forming
reaction has been elucidated in Scheme 6. The reaction may proceed through the
formation of imino resonance structure (A) showing the increased reactivity of the
endocyclic nitrogen atom in the heteroaromatic ring.24,25 The attack of imino nitrogen on
the protonated carbonyl carbon of the aldehydic group leads to intermediate B, which
gives rise to product 3 (Scheme 6).
8

H
N
H
N
N
S
NH2
NH2
NH2
S
S
Amino form
Imino form (A)
-H
H
N
Br
NH
S
HO
1
Br
H
N
N
S
H
N
NH
O
-HBr
S
3
B
O
H
Scheme 6. A plausible mechanism for the reaction
Next aiming diversity in strategy, we then speculated the reaction of 1 with
various aromatic amines. Unfortunately, most of the anilines did not result in the desired
isochroman products. In the case of aniline, the reaction of 2-(2-
bromoethyl)benzaldehyde 1 in AcOH (at 80 oC), produced N-phenyl dihydroisoquinoline
6 (m/z 208) and 1-acetyl N-phenyl dihydroisoquinoline 5 (m/z 267). Under similar
conditions, p-chloro aniline gave a mixture of two compounds, dihydroisocoumarin 8 and
1-acetyl N-phenyl tetrahydrohydroisoquinoline 7. Tert-butylsulfonamide yielded a
mixture of dihydroisocoumarin 8 and N-protected dihydroisoquinoline 9. Similarly, in the
case of p-acetylaniline, we could only isolate traces of 1-substituted isochroman 10 along
with dihydroisocoumarin 8. p-nitroaniline gave N-(4-nitrophenyl)isochroman-1-amine
3n, whereas the formation of tetrahydroisoquinoline was not detected as reported in
DCE.20 These compounds were analysed by 1H NMR (8, 7, 9, 10) and Mass (5, 6). There
were no consistent results (Scheme 7) and no appropriate yields with the aromatic
amines, except for few anilines with withdrawing groups led to the formation of
substituted isochromans.
9

Scheme 7. Reaction with varied amines
Biological Activity:
ANTIBACTERIAL ACTIVITY BY PAPER DISC METHOD: 26
All the synthesized isochromans derivatives, 3a-n were screened for their
antibacterial activity (Table 5, Figure 3) against different types of bacterial strains they
are Gram positive bacterial strains of Staphylococcus aureus, Bacillus subtilis,, Gram
negative bacterial strains of Escherichia coli and Pseudomonas aeruginosa at a
concentration of 1.0 µg/mL. Some of the synthesized compounds showed high activity
and some showed moderate activity compared to standard drug positive controls
Norfloxacin and ofloxacin at a concentration of 1.0 µg/mL.
10

Table 5: Antibacterial activity of isochromans (3a-n)
Zone of inhibition in (mm)
Sample No
Escherichia coli
Pseudomonas aeruginosa
Staphylococcus aureus
Bacillus subtilis
3
4
2.5
5
3
3a
2.5
2.5
4
5
2.5
2.5
4.5
7.5
2.5
2.5
2.5
3
3b
2.5
3
2.5
2.5
6
3c
3d
6.5
2.5
2.5
2.5
3
5
3e
2.5
3
2.5
3
3f
3g
3
2.5
3
3h
4
3i
6
5
3
2.5
6
3j
3.5
3
4.5
6
3
3k
4.5
4
4
3l
3.5
4.5
5
3
3m
4
3
5
3n
Norfloxacin
Ofloxacin
9.5
7
11
10
E.coli
P.aeruginosa
S.aureus
B.subtilis
10
8
6
4
2
0
Compounds
Figure 3. Antibacterial activity of compounds 3a-n against Echerichia coli, Pseudomonas aeruginosa
Staphylococcus aureus and Bacillus subtilis. Micro organisms were screened using potato dextrose agar
with Echerichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis are showing
zone of inhibition (mm) with different concentration of compound.
The antibacterial activity of substituted benzo[d]thiazol-2-amine isochromans
like 3e (R1 = 6-Ethoxy benzo[d]thiazol), and 3b (R1 = -6-Bromo benzo[d]thiazol), 2-
aminothiazole isochroman compounds such as 3j (R1 = -F-benzene), and 2-amino
11

pyridine substitute isochroman compounds such as 3m (R1 = -Bromo Pyridine), 3k (R1
= 5-Iodo Pyridine), 3l (R1 = 6-Methyl Pyridine), and simple 4-nitro amino substitute 3n
(R1 = -4-NO2) showed good zone of inhibition against Staphylococcus aureus, Bacillus
subtilis, Echerichia coli, and Pseudomonas aeruginosa compared to the standard drugs
at a concentration of 1mg/ mL.Whereas the compounds 3a, 3c, 3d, 3f, 3g, 3h, and 3i
were showing moderate activity against all the bacterial strains when compared to
standard drugs at a concentration of 1.0 mg/ mL. It leads us to conclude that from Table 5
and Figure 3, Benzo[d]thiazol-2-amine isochromans, aminothiazoles isochromans, and
Pyridine isochromans showed higher zone of inhibition when compared with other
compounds.
All the synthesized isochroman derivatives have been tested for anti-bacterial
activity. All the synthesized compounds have tested in vitro for their antibacterial
(Staphylococcus aureus, Bacillus subtilis, Echerichia coli, Pseudomonas aeruginosa)
activities. Compounds 3e, 3n, 3m, 3l, 3k, 3j and 3b, were showed most potent in vitro
activity against bacterial strains.
In summary, we have developed for the first time a mild, efficient and metal-free
protocol for the synthesis of library of 22 new N-based heterocycles which are of interest
in several fields for their biological properties and synthetic utility. We have
demonstrated an unparalleled construction of two privileged heterocyclic rings in one pot
in better yields by easy isolation without tedious workup. Readily accessible starting
material, remarkably considerable reaction time, implicity in operation and cost effective,
makes this method innovative and attractive. The in vitro antibacterial evaluation showed
that most of the synthesized isochroman derivatives exhibited moderate to good zone of
inhibition. From the antibacterial activity results of isochromans it is interesting to note
that substituents like Ethoxy benzo[d]thiazol-2-amine, Fluoro 2-aminothiazoles and 2-
amino pyridine like methyl, iodo substituents shows better antibacterial compared to
other substituted compounds. Noticeably, compound 3e, 3n, 3m, 3l, 3k, 3j and 3b were
most potent compound in vitro activity against bacterial strains. These findings
demonstrated that isochromans have biological significance.
12

Acknowledgements
N.F. thank the DST (SR/WOS-A/CS-124/2012), India for providing financial support in
the form of fellowship. Further, B.V.S, G.S and J.S.Y thanks CSIR, New Delhi, India for
financial support as part of XII Five Year plan programme entitled ORIGIN (CSC-0108).
Supplementary Data
EXPERIMENTAL SECTION
1
General Information H NMR spectra were measured on 400 MHz and 500 MHz
spectrometers. Chemical shifts were recorded as follows: chemical shift in ppm from
internal tetramethylsilane on the δ scale, multiplicity (s = singlet; d = doublet; t = triplet;
q = quartet; m = multiplet; dd = doublet of doublets; ddd = doublet of doublet of
doublets; br = broad), coupling constant (Hz), integration, and assignment. 13C NMR
spectra were measured on 100 MHz and 125 MHz spectrometers. Chemical shifts were
recorded in ppm from the solvent resonance employed as the internal standard
(deuterochloroform at 77.0 ppm). High-resolution mass spectra (HRMS) were measured
on orbitrap mass spectrometers. Characteristic peaks in the infrared (IR) spectra were
recorded in wave numbers, cm−1. Melting points were determined on an Electro thermal
melting point apparatus and are uncorrected. Thin-layer chromatography (TLC) was
performed using 0.25 mm silica gel plates (60F-254). The products were purified by short
column chromatography on silica gel 60-120 or 100− 200 mesh.
General procedure for the preparation of 3a-12n. Mixture of 2-(2-
bromoethyl)benzaldehyde 1 (0.1g, 0.0047 mmol) and 4-methoxybenzo[d]thiazol-2-
o
amine 2b (0.102 g, 0.0056 mmol) in 3.0 mL of acetic acid was stirred at 80 C for 4 h,
after cooling to room temperature, the reaction mixture was poured into saturated
aqueous NaHCO3, and the resulting mixture was extracted with EtOAc three times. The
combined organic extracts were washed with brine, dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. The residue was purified by flash
column chromatography on silica gel to afford pure isochroman 3b (0.107g, 73%) and
isoquinolinone 10b (0.029g, 20%).
13

N-(isochroman-1-yl)-4-methoxybenzo[d]thiazol-2-amine (3a): white solid (0.107g,
73%); m.p 189-192 °C ;1H NMR (400 MHz, CDCl3): δ 7.17-7.31 (m, 5H), 7.12 (t, J =
8.08Hz, 1H), 6.84 (dd, J= 0.61, 8.08 Hz, 1H), 6.31 (brs, 1H), 6.13 (s, 1H), 4.09-4.16 (m,
13
1H), 3.96-4.01 (m, 4H), 2.97-3.06 (m, 1H), 2.76 (dt, J = 3.66, 16.47 Hz, 1H). C NMR
(100 MHz, CDCl3): δ 165.0, 151.0, 140.8, 134.6, 133.0, 132.0, 128.9, 128.5, 126.7,
126.4, 122.8, 113.2, 106.9, 81.3, 59.0, 55.7, 27.8. IR (KBr): 3449, 2925, 1559, 1497,
1256, 1084, 1040, 731 cm-1. HRMS-E SI (m/z): [M + H]+ calcd for C17H17N2O2S,
313.1005; found, 313.1008.
2-(4-methoxybenzo[d]thiazol-2-yl)-3,4-dihydroisoquinolin-1(2H)-one (4a): yellow solid
1
(0.029g, 20%); m.p 192-194 °C H NMR (400 MHz, CDCl3): δ 8.22 (dd, J = 7.82, 1.1
Hz, 1H), 7.55 (td, J =7.45, 1.46 Hz, 1H), 7.45 (m, 2H), 7.30 (m, 2H), 6.92 (dd, J = 7.94,
0.73 Hz, 1H), 4.79 (t, J = 6.48, 6.60 Hz, 2H), 4.06 (s, 3H), 3.19 (t, J = 6.48, 6.60 Hz, 2H);
13C NMR (125 MHz, CDCl3): δ 163.7, 158.4, 152.0, 138.9, 133.2, 129.1, 128.7, 128.1,
127.5, 127.2, 124.8, 123.0, 113.3, 106.5, 55.9, 45.6, 27.7. IR (KBr): 2924, 1656, 1465,
1257, 734 cm-1. HRMS-ESI (m/z): [M + Na]+ calcd for C17H14N2NaOS, 333.0668; found,
333.0683.
6-bromo-N-(isochroman-1-yl)benzo[d]thiazol-2-amine (3b): off white solid (0.128g,
1
75%); m.p 212-214 °C; H NMR (400 MHz, CDCl3): δ 7.74 (s, 1H), 7.24-7.40 (m, 5H),
7.19 (d, J = 7.31, 7.33 Hz, 1H), 6.60 (brs, 1H), 6.23 (s, 1H), 4.10 (m, 1H), 4.01 (m, 1H),
13
3.01 (m, 1H), 2.77 (dt, J = 3.54, 16.6 Hz, 1H); C NMR (125 MHz, CDCl3): δ 166.4,
150.4, 134.8, 139.9, 132.9, 129.1, 129.0, 128.6, 126.8, 126.6, 123.2, 120.5, 114.5, 81.0,
59.4, 27.9; IR (KBr): 3448, 2985, 1610, 1445, 1078, 1041, 813, 750 cm-1; HRMS-ESI
(m/z): [M + Na]+ calcd for C16H13 BrNaN2OS, 382.9854; found, 382.9824.
2-(6-bromobenzo[d]thiazol-2-yl)-3,4-dihydroisoquinolin-1(2H)-one (4b): white solid (
0.037 g, 22%); m.p 228-230 °C; 1H NMR (500 MHz, CDCl3): δ 8.21 (dd, J = 1.22, 8.07
Hz, 1H), 7.97 (d, J = 1.95, Hz, 1H), 7.70 (d, J = 8.68 Hz, 1H), 7.52-7.58 (m, 2H), 7.45
(t, J = 8.06 Hz, 1H), 7.32 (d, J = 7.54, 1H), 4.71 (t, J = 6.48, 2H), 3.22 (t, J = 6.48 Hz,
2H); 13C NMR (100 MHz, CDCl3): δ 163.8, 159.7, 147.1, 138.8, 138.8, 135.3, 133.4,
129.2, 127.9, 127.6, 127.3, 123.6, 122.4, 116.8, 45.6, 27.6; IR (KBr): 2922, 1648, 1493,
1464, 1404, 1279, 1253, 1161, 1053, 969, 808, 740, cm-1 HRMS-ESI (m/z): [M + Na]+
calcd for C16H11 BrNaN2OS, 380.9668; found, 380.9681.
14

N-(isochroman-1-yl)-6-(trifluoromethyl)benzo[d]thiazol-2-amine (3c) : white solid
1
(0.116 g, 70%); m.p 202-204 °C H NMR (400 MHz, CDCl3): 7.91 (s, 1H), 7.50 (dd, J =
7.82, 1.22 Hz, 1H), 7.28 (m, 5H), 6.99 (brs, 1H), 6.25 (s, 1H), 4.09 (m, 1H), 4.02 (m,
1H), 3.02 (m, 1H), 2.73 (dt, J = 3.17, 16.6 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 168.3,
154, 138.8, 134.8, 132.8, 130.1(q, J = 275 Hz), 129.1, 128.7, 126.8, 126.6, 125.4 (q, J =
272.3 Hz), 119.3, 123.2 (q, J = 3.9 Hz), 118.3 (q, J = 3.9 Hz), 81.0, 59.4, 27.9; IR (KBr):
3406, 2923, 1614, 1595, 1452, 1325, 1286, 1111, 1079, 841, 766, 706 cm-1; HRMS-ESI
(m/z): [M + H]+ calcd for C17H14F3N2OS, 351.0773, found, 351.0758.
2-(6-(trifluoromethyl)benzo[d]thiazol-2-yl)-3,4-dihydroisoquinolin-1(2H)-one (4c) : off
1
white solid (0.029 g, 18%); m.p 243-245 °C; H NMR (500 MHz, CDCl3): δ 8.23 (dd, J
= 7.82, 1.1 Hz, 1H), 8.12 (s, 1H), 7.93 (d, J = 8.43 Hz, 1H), 7.68 (dd, J = 1.46, 8.31 Hz,
1H), 7.57 (td, J = 1.34, 7.45 Hz, 1H), 7.46 (td, J = 0.48, 6.96 Hz, 1H), 7.34 (d, J = 7.58
Hz, 1H), 4.74 (t, J = 6.48, 2H), 3.24 (t, J = 6.48 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ
164, 161.7, 150.4, 138.9, 133.7, 133.6, 130.9 (q, J = 30.8 Hz), 129.3, 127.8, 127.7, 127.4,
123(q, J = 3.7 Hz), 121.9 (q, J = 272.2 Hz), 121.3, 118.8 (q, J = 4.4 Hz), 45.7, 27.7; IR
(KBr): 2923, 1660, 1497, 1325, 1286, 1162, 1130, 828, 741 cm-1; HRMS-ESI (m/z): [M
+ H]+ calcd for C17H12N2OSF3, 348.0622, found, 348.0233.
6-fluoro-N-(isochroman-1-yl)benzo[d]thiazol-2-amine (3d): yellow solid (0.1g, 71%);
m.p 190-193 °C; 1H NMR (400 MHz, CDCl3): δ 7.48 (m, 1H); 7.24-7.38 (m, 4H), 7.19
(dd, J = 0.48, 7.34 Hz, 1H), 7.05 (m, 1H), 6.41 (brs, 1H), 6.25 (s, 1H), 4.12 (m, 1H), 4.01
(m, 1H), 3.01 (m, 1H), 2.78 (dt, J = 3.05, 16.75 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ
165.5, 158.6 (d, J = 240.7 Hz), 147.9, 134.8, 133.5, 131.4(d, J = 10.9 Hz), 133.0, 129,
126.8, 126.6, 120.1(d, J = 8.2 Hz), 113.7(d, J = 23.6 Hz), 107.5(d, J = 27.3 Hz), 80.9,
59.3, 27.9; IR (KBr): 3447, 2924, 1616, 1568, 1460, 1327, 1248, 1153, 1094, 1080, 853,
809, 751cm-1 HRMS-ESI (m/z): [M + Na] + calcd for C16H13 FN2NaOS, 323.0623; found,
323.0625.
2-(6-fluorobenzo[d]thiazol-2-yl)-3,4-dihydroisoquinolin-1(2H)-one (4d): yellow solid
(0.031g, 23%); m.p 164-166 °C; 1H NMR (400 MHz, CDCl3): δ 8.21 (dd, J = 7.70, 0.85
Hz, 1H), 7.78 (dd, J = 4.64, 8.80 Hz, 1H), 7.51-7.58 (m, 2H), 7.43 (t, J = 7.34 Hz, 1H),
7.32 (d, J = 7.45 Hz, 1H), 7.17 (td, J = 2.56, 9.04 Hz, 1H), 4.70 (t, J = 6.48, 2H), 3.22 (t,
J = 6.48 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 163.8, 161.2, 159.0, 144.6, 138.8,
134.6 ( d, J = 10.5 Hz), 133.4, 129.2, 128, 127.6, 127.3, 122 (d, J = 8.8 Hz), 114 (d, J =
15

24.2 Hz), 107.3(d, J = 26.4 Hz), 45.7, 27.6; IR (KBr): 2924, 1659, 1601, 1460, 1396,
1318, 1240, 1192, 1157, 965, 846, 743, 696 cm-1 HRMS-ESI (m/z): [M + Na] + calcd for
C16H11 FN2NaOS, 321.0468; found, 321.0478.
6-ethoxy-N-(isochroman-1-yl)benzo[d]thiazol-2-amine (3e): yellow solid (0.118g,
77%); m.p 186-188 °C; 1H NMR (400 MHz, CDCl3): δ 7.50 (dd, J = 8.80, 2.07, 1H), 7.16
(m, 5H), 6.92 (dd, J = 2.56, 8.80 Hz, 1H), 6.24 (s, 1H), 6.01 (brs, 1H), 3.97-4.17 (m, 4H),
3.78 (dt, J = 16.5, 3.91 Hz, 1H), 3.02 (m, 1H), 1.42 (t, J = 6.96 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ 171.8, 154.9, 134.7, 133.6, 133.3, 130.4, 128.9, 128.4, 126.7, 126.7,
126.7, 114.4, 105.9, 80.9, 64.1, 59.2, 27.9, 14.9; IR (KBr): 3446, 2923, 1607, 1459, 1258,
1025, 746 cm-1 HRMS-E SI (m/z): [M + H] + calcd for C18H19N2O2S, 327.1162; found,
327.1180.
2-(6-ethoxybenzo[d]thiazol-2-yl)-3,4-dihydroisoquinolin-1(2H)-one (4e) : yellow solid
1
(0.032g, 21%); m.p 140-142 °C; H NMR (400 MHz, CDCl3): δ 8.22 (dd, J = 7.78, 1.06
Hz, 1H), 7.73 (d, J = 8.85Hz, 1H), 7.53 (td, J = 7.47, 1.37 Hz, 1H), 7.43 (t, J = 7.32Hz,
1H), 7.32 (m, 2H), 7.04 (dd, J =2.59, 8.85 Hz, 1H), 4.69 (t, J = 6.56 Hz, 2H), 4.12 (q, J
= 7.01, 14.0 Hz, 2H), 3.21 (t, J = 6.56 Hz, 2H), 1.46 (t, J = 7.01 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ 163.5, 157.5, 156.1, 142.2, 138.7, 134.7, 133.1, 129.0, 128.2, 127.5,
127.2, 121.7, 115.5, 104.5, 64.0, 45.5, 27.7, 14.8; IR (KBr): 2923, 1658, 1599, 1460,
1401, 1237, 1160, 816, 738, 692cm-1; HRMS-E SI (m/z): [M + H]+ calcd for
C18H17N2O2S, 325.1005; found, 325.1024
N-(isochroman-1-yl)-6-methylbenzo[d]thiazol-2-amine (3f) :off white solid (0.019g,
72%); m.p 200-202 °C 1H NMR (400 MHz, CDCl3): δ 7.43 (s, 1H), 7.16-7.34 (m, 5H),
7.08 (d, J = 8.2 Hz, 1H), 6.63 (brs, 1H), 6.24 (s, 1H), 4.10 (td, J = 3.45, 10.63 Hz, 1H),
13
3.99 (m, 1H), 2.99 (m, 1H), 2.753 (dt, J = 3.54, 16.6 Hz, 1H), 2.41 (s, 3H); C NMR
(100 MHz, CDCl3): δ 65.4, 149.3, 134.8, 133.3, 131.8, 130.7, 128.9, 128.4, 127.1, 126.7,
126.7, 120.8, 119.0, 81.0, 59.3, 27.9, 21.2; IR (KBr): 3348, 2972, 1547, 1459, 1239,
+
1082, 986, 677cm-1 . HRMS-E SI (m/z): [M + H] calcd for C17H17N2OS, 297.1056;
found, 297.1056.
2-(6-methylbenzo[d]thiazol-2-yl)-3,4-dihydroisoquinolin-1(2H)-one (4f): yellow solid
(0.0189 g, 15%); m.p 220-222 °C 1H NMR (500 MHz, CDCl3): δ 8.21 (dd, J = 7.78, 1.06
Hz, 1H), 7.73 (d, J = 8.24 Hz, 1H), 7.64(s, 1H), 7.54 (td, J = 7.32, 1.37Hz, 1H), 7.44 (td,
J = 7.93, 0.76 Hz, 1H), 7.31 (t, J =7.32 Hz, 1H), 7.25 (m, 1H), 4.72 (t, J = 6.71 Hz, 2H),
16

13
3.21 (t, J = 6.56 Hz, 2H), 2.49 (s, 3H); C NMR (100 MHz, CDCl3): δ 163.7, 158.7,
146.1, 138.9, 133.9, 133.2, 129.1, 127.5, 127.25, 127.5, 120.9, 120.7.0, 45.55, 27.7, 21.5;
IR (KBr): 2924, 1742, 1599,1462, 1280, 1019, 817, 740 cm-1 .HRMS-ESI (m/z): [M + H]
+ calcd for C17H15 N2OS, 295.0827; found, 295.0901.
N-(isochroman-1-yl)benzo[d]thiazol-2-amine (3g): yellow solid (0.094 g, 71%); m.p
243-245 °C 1H NMR (500 MHz, CDCl3): δ 7.65 (dd, J = 0.85, 7.82 Hz, 1H), 7.59 (d, J =
8.07 Hz, 1H), 7.36-7.24 (m, 4H), 7.20-7.14 (m, 2H), 6.37,(brs, 1H), 6.27 (s, 1H), 4.15-
4.11 (m, 1H), 4.03-3.99 (m, 1H), 3.09-2.97 (m, 1H), 2.78 (dt, J = 3.66, 16.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3): δ 166.5, 150.3, 134.7, 132.9, 132.3, 129.2, 129.0, 128.6, 126.8,
126.7, 123.29, 120.5, 114.65, 81.0, 59.4, 27.91; IR (KBr): 3352, 2965, 1598, 1457, 1243,
+
1085, 988, 676 cm-1. HRMS-ESI (m/z): [M + H] calcd for C16H15N2OS, 283.0824;
found, 283.0897.
2-(benzo[d]thiazol-2-yl)-3,4-dihydroisoquinolin-1(2H)-one (4g): yellow solid. (0.023g,
1
18%); m.p 213-217 °C H NMR (500 MHz, CDCl3): δ 8.23 (dd, J = 1.22, 7.3 Hz, 1H);
7.86 (dt, J = 9.15, 0.92, 2H), 7.55 (td, J = 1.37, 1.74, 1H), 7.45 (m, 2H), 7.33 (t, J = 7.32,
2H), 4.74 (t, J = 6.40, 2H), 3.22 (t, J = 6.56 Hz, 2H); HRMS-ESI (m/z): [M + H]+ calcd
for C16H13N2OS, 281.0743; found, 281.0753.
N-(isochroman-1-yl)-5-methyl-4-phenyl-4,5-dihydrothiazol-2-amine (3h): yellow solid
(0.109g, 72%); m.p 192-195 °C; 1H NMR (400 MHz, CDCl3): δ 7.58 (dd, J = 1.34, 8.43
Hz, 2H), 7.39 (t, J = 7.33 Hz, 2H), 7.19-7.33(m, 4H), 7.15(d, J = 7.45 Hz, 1H), 6.07( brs,
2H), 4.07-4.15 (m, 2H), 2.92 (m, 1H), 2.74 (dt, J = 3.54, 16.5 Hz, 1H), 2.44 (s, 3H); 13C
NMR (125 MHz, CDCl3): δ 163.4, 146.0, 135.2, 134.6, 133.5, 128.8, 128.3, 128.3, 128.1,
127.1, 126.6, 126.5, 117.5, 81.5, 59.0, 27.9, 12.3; IR (neat): 3195, 2923, 1545, 1450,
1309, 1327, 1244, 1161, 1082, 1036, 740, 694 cm-1; HRMS-ESI (m/z): [M + H] + calcd
for C19H19N2OS, 323.1213; found, 323.1219.
2-(5-methyl-4-phenyl-4,5-dihydrothiazol-2-yl)-3,4-dihydroisoquinolin-1(2H)-one (4h):
yellow solid (0.033g, 22%); m.p 167-170 °C; 1H NMR (500 MHz, CDCl3): δ 8.19 (dd, J
= 1.07, 7.72Hz, 1H), 7.71 (dd, J = 1.37, 8.08 Hz, 2H), 7.51 (td, J = 1.37, 7.47 Hz, 1H),
7.40-7.47 (m, 3H), 7.31(tt , J = 1.22, 7.32 Hz, 2H), 7.29 (d, J = 7.63 Hz, 1H), 4.63 (t, J =
13
6.71 Hz, 2H), 3.16 (t, J = 6.56 Hz, 2H), 2.55 (s, 3H); C NMR (125 MHz, CDCl3): δ
162.9, 155.1, 144.3, 132, 128.8, 128.3, 128.3, 128.1, 127.1, 126.6, 126.5, 117.5, 121.5,
127.1, 127.4, 123.6, 44.6, 27.6, 12.1; IR (neat): 2920, 1649, 1490, 1400, 1318, 1243,
17

+
1166, 1017, 690 cm-1 . HRMS-ESI (m/z): [M + H] calcd for C19H17N2OS, 321.1056;
found, 321.108.
5-(2,4-difluorophenyl)-N-(isochroman-1-yl)thiazol-2-amine (3i): yellow solid (0.123g,
76%) m.p 183 °C; 1H NMR (500 MHz, CDCl3): δ 8.04 (dd, J = 1.67, 8.69 Hz, 1H), 7.20-
7.32 (m, 3H), 7.15 (d, J = 7.63 Hz, 1H), 7.05 (d, J = 2.13 Hz, 1H), 6.83-6.92 (m, 2H),
6.22 (brs, 1H), 6.12 (d, J = 7.32, 1H), 4.12 (td, J = 3.66, 10.68 Hz, 1H), 2.95-4.00 (m,
1H), 2.96-3.03 (m, 1H), 2.75 (dt, J = 2.89, 16.63 Hz, 1H);13C NMR (100 MHz, CDCl3): δ
166.2, 161.8 (dd, J = 249.4, 11.7Hz), 160.3 (d, J = 252.4, 11.7 Hz), 156.2, 143.8, 134.7,
133.3, 130.7 (dd, J = 8.8, 9.5 Hz), 128.9, 128.4, 126.6 (d, J = 1.5 Hz), 118.9 (d, J =
11.0Hz), 111.3 (dd, J = 21.3, 2.9 Hz), 107 (d, J = 14.7Hz), 104.1 (d, J = 26.4 Hz), 81.4,
59.0, 27.9; IR (neat): 3415, 2924, 1624, 1553, 1483, 1327, 1262, 1027, 735 cm-1 .
HRMS-ESI (m/z): [M + H] + calcd for C18H15F2N2OS, 345.0868; found, 345.0879
5-(4-fluorophenyl)-N-(isochroman-1-yl)thiazol-2-amine (3j): yellow solid.(0.123g,
75%); m.p 187-189 °C; 1H NMR (400 MHz, CDCl3): δ 7.71-7.76 (m, 2H), 7.09-7.23 (m,
5H), 6.93 (d, J = 7.58 Hz, 1H), 5.92 (s, 1H), 5.00 (brs, 2H), 4.25-4.31(m, 1H), 3.92-3.99
(m, 1H), 3.03-3.12 (m, 1H), 2.80 (dt, J = 4.15, 16.38 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ 163.4, 159.7 (d, J = 243.7 Hz), 159.1, 144.6, 138.8, 134.6 (d, J = 10.5 Hz),
133.4, 129.2, 128, 127.6, 127.5, 127.3, 122.1(d, J = 8.8 Hz), 114.4(d, J = 24.2 Hz), 107.3
(d, J = 26.1 Hz), 77.2, 45.6, 27.7; IR (KBr): 3438, 2926, 1634, 1530, 1497, 1221, 1081,
844, 738 cm-1 . HRMS-ESI (m/z): [M + H] + calcd for C18H16FN2OS, 327.0962; found,
327.0962.
5-iodo-N-(isochroman-1-yl)pyridin-2-amine (3k): yellow solid, (0.13g, 78%); m.p 152-
154 °C; 1H NMR (400 MHz, CDCl3): δ 8.26 (d, J = 1.37 Hz, 1H), 7.73 (dd, J = 2.32, 8.68
Hz, 1H), 7.15-7.30 (m, 4H), 6.6 (d, J = 8.80 Hz, 1H), 6.24 (d, J = 7.82 Hz, 1H), 5.43-5.49
(d, J = 7.47 Hz, 1H), 4.04-4.17 (m, 1H), 3.90-3.97 (m, 1H), 2.92-3.00 (m, 1H), 2.78 (dt, J
= 3.91, 16.62 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 156.1, 153.7, 145.4, 134.8, 134.3,
128.9, 128.1, 126.6, 126.5, 109.9, 78.4, 58.9, 28.4; IR (KBr): 3216, 2923, 1577, 1502,
1456, 1371, 1308, 1271, 1075, 1035, 985, 741, 616 cm-1 HRMS-ESI (m/z): [M + H]+
calcd for C14H14IN2O, 353.0145; found, 353.0159.
2-(5-iodopyridin-2-yl)-3,4-dihydroisoquinolin-1(2H)-one (4k): yellow solid, (0.034g,
21%; ) m.p 128-130 °C; 1H NMR (300 MHz, CDCl3): δ 8.62 (s, 1H), 8.17 (d, J = 7.70
Hz, 1H), 7.90-8.00 (m, 2H), 7.49 (t, J = 7.42, 7.97 Hz, 1H), 7.39 (t, J = 7.42, 7.97 Hz,
18

13
1H), 7.23-7.30 (m, 1H), 4.28 (t, J = 6.32 Hz, 2H), 3.11 (t, J = 6.32 Hz, 2H); C NMR
(100 MHz, CDCl3): δ 164.7, 153.3, 153.3, 144.8, 139.1, 132.5, 128.9, 127.2, 127.0,
121.6, 92.7, 87.1, 45.4, 28.3; IR (KBr): 2926, 1662, 1556, 1459, 1391, 1358, 1292, 1152,
828, 738, 625 cm-1 HRMS-E SI (m/z): [M + H]+ calcd for C14H12IN2O, 349.9916; found,
349.9980.
N-(isochroman-1-yl)-6-methylpyridin-2-amine (3l): yellow solid, (0.084g, 74%); m.p
1
120-122 °C; H NMR (500 MHz, CDCl3): 7.45 (t, J = 7.70 Hz, 1H), 7.13-7.33(m, 5H),
6.60 (m, 1H), 6.22 (d, J = 7.97 Hz, 1H), 5.42 (d, J = 7.92 Hz, 1H), 4.09-4.19 (m, 1H),
13
3.88-3.97 (m, 1H), 2.97 (m, 1H), 2.76 (dt, J = 3.85, 16.50 Hz, 1H), 2.40 (s, 3H); C
NMR (100 MHz, CDCl3): δ 157.0, 156.6, 140.4, 134.7, 128.7, 128.2, 127.9, 126.7, 126.3,
114.1, 103.9, 78.8, 58.6, 28.2, 24.2; IR (KBr): 3223, 2923, 1588, 1457, 1319, 1269, 1118,
1075, 1045, 981, 778, 637 cm-1 HRMS-ESI (m/z): [M + H]+ calcd for C15H17N2O,
241.1335; found, 241.1351.
2-(2-((5-bromo-3-methylpyridin-2-yl)amino)ethyl)benzaldehyde (3m): yellow solid,
(0.134g, 89%); m.p 127-133 °C; 1H NMR (500 MHz, CDCl3): δ 10.22 (s, 1H), 8.04 (d, J
= 2.28 Hz, 1H), 7.83 (dd, J = 1.37, 7.78 Hz, 1H), 7.53 (dt, J =1.37, 7.62 Hz, 1H), 7.42
(td, J =1.06, 7.47 Hz, 1H), 7.31 (d, J = 7.39 Hz, 1H), 7.29 (m, 1H), 4,51 (brs, 1H) 3.71
(m, 2H), 3.36 (t, J = 6.86 Hz, 2H), δ 1.98 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 193.4,
155.3, 145.7, 142.3, 138.8, 133.8, 132.8, 131.7, 127.0, 118.6, 115.9, 115.9, 106.2, 89.6,
43.5, 32.1, 16.7; IR (KBr): 3401,1673, 1593, 1462, 889, 775 cm-1. HRMS-ESI (m/z): [M
+ H]+ calcd for C15H16BrN2O, 319.0368; found, 319.0435.
N-(4-nitrophenyl)isochroman-1-amine (3n): yellow solid (0.103g, 81%). m.p 168-170
°C; 1H NMR (500 MHz, CDCl3): 8.15 (d, J = 1.52, 9.0Hz, 2H), 7.18-7.36 (m, 4H), 6.86
(d, J = 9.17 Hz, 2H)6.08 (d, J = 7.02 Hz, 1H), 5.20 (brs, 1H), 4.07-4.12 (m, 1H), 3.92-
3.97 (m, 1H), 3.01 (m, 1H), 2.77 (dt, J = 3.66, 16.63 Hz, 1H). 13C NMR (125 MHz,
CDCl3): δ 151.7, 139.6, 134.8, 133.7, 129.1, 129.1, 128.5, 126.7, 126.4, 126.1, 112.9,
112.9, 79.2, 58.6, 27.9; IR (KBr) 3404, 2916, 1597, 1466, 1309, 1253, 1181, 1077, 990,
862, 837, 749 cm-1; HRMS-ESI (m/z): [M + H]+ calcd for C15H15N2O3, 271.1077; found,
271.1081.
Antibacterial activity by Paper Disc method:
The antibacterial activity of synthesized compounds was conducted against two gram
positive bacteria viz., Bacillus subtilis , Staphylococcus aureus, and two gram negative
19

bacteria viz., Pseudomonas aeruginosa, Escherichia coli by using paper disc method.
Norfloxacin and ofloxacin were employed as standard to compare the results.
Media Preparation:
0
LB Broth: NaCl: 10 g /Lit, Tryptone: 10 g/lit, Yeast Extract: 5g/lit, Autoclave at 121 c
and 15 lb Pressure.
LB agar: NaCl: 10 g/Lit, Tryptone: 10 g/lit, Yeast Extract: 5gr/lit, Agar Agar: 15 gr /lit .
The above constituents were weighed and dissolved in water. The mixture was warmed
on water bath till agar dissolved. This was then sterilized in an autoclave at 15 lbs
0
pressure and 121 C for fifteen minutes. The sterilized medium (20 ml) was poured in
sterilized Petri dishes under aseptic condition, allowing them to solidify on a plane table.
Bacterial Strains:
Inoculum’s preparation
The inoculum was standardized at 1* 106 CFU/ml comparing with turbidity standard (0.5
MacFarland tube)
Pseudomonas aeruginosa (gram-negative) MTCC – 424, Escherichia coli (E. coli)
(gram-negative) MTCC – 443, Bacillus subtilis (Gram-positive) MTCC– 441,
Staphylococcus aureus (gram-positive) MTCC – 96.
Swabs preparation
A supply of cotton wool swabs on wooden applicator sticks was prepared. They
were sterilized in tins, culture tubes, or on paper, either in the autoclave or by dry heat.
5 mm disks were prepared by using wt men filter paper and autoclaved
Methodology:
Inoculation of Pseudomonas aeruginosa (gram-negative), Escherichia coli (E.
coli) (gram-negative), Bacillus subtilis (Gram-positive), Staphylococcus aureus (gram-
positive ) all microbes obtain from Microbial Type Culture Collection –MTCC In auto
calved LB broth media and Incubate over night at 37º C in shaker for Bacterial growth.
From that 0.2ml of bacterial culture was taken and inoculated by using spreader on
freshly prepared auto calved agar plates i.e Petri dishes. After drying of plate 5 mm
sample disc which are dissolved in DMSO solvent were kept on microbial plate along
with positive controls NX (Norfloxacin) for Staphylococcus, Pseudomonas and OF
20

(ofloxacin) for Bacillus and E.coli. Incubation over night at 37º C in BOD incubator.
After overnight incubation zone of inhibition is measured by measuring scale.
References and Notes
1
2
For a review, see: a) A. R. Dick, M. S. Sanford, Tetrahedron 2006, 62, 2439–2463; b) J. Du Bois,
Chemtracts 2005, 18, 1–13; c) C. G. J. Espino, Du Bois, In Modern Rhodium-Catalyzed Organic
Reactions, P. A. Ed. Evans, Wiley-VCH: Weinheim, 2005, 379-416; d) J. A. Halfen Curr. Org. Chem.
2005, 9, 657–669.
For selected reviews on amination reaction, see: a) H.M. Guo, C. Xia, H.-Y. Niu, X.-T. Zhang, S-N.
Kong, D-C. Wang, G-R. Qu, . Adv. Synth. Catal. 2011, 353, 53; b) K. Sun, X.Wang, G. Li, Z. Zhu, Y. Jiang,
B. Xiao, Chem. Commun. 2014, 50, 12880; c) M. Johannsen, K.A.Jørgensen, Chem. Rev. 1998, 98,
1689; d) H. Aruri, U. Singh, S. Sharma, S. Gudup, M. Bhogal, S. Kumar, D. Singh, V.K. Gupta, R. Kant,
R. A. Vishwakarma, P. P. Singh, J. Org. Chem. 2015, 80, 1929; e) P. Dauban, R.H. Dodd, Synlett 2003
,
1571; f) S. V. Ley, A.H. Thomas, Angew. Chem. Int. Ed. 2003, 42, 5400; g) H. M. LDavies, M. S. Long,
Angew. Chem. Int. Ed. 2005, 44, 3518; h) M-L. Louillat, F. W. Patureau, Chem. Soc. Rev. 2014, 43,
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22

Synthesis and biological evaluation of 1-amino isochromans from 2-bromoethyl
benzaldehyde and amines in acid medium
Narjis Fatima,a,* B. V. Subba Reddy,a Gowravaram Sabitha,a J. S. Yadav,a K. Sudhakarbb and Chandra
Shekar Puttab
aCenter for Semiochemicals, Natural Products Chemistry Division, CSIR-Indian
Institute of Chemical Technology, bOsmania University, Hyderabad,500 007, India
E-mail: dr.narjisiict@yahoo.com ; Fax: +91-40-27160512
.
Graphical Abstract
Br
AcOH
H2N
Hetero
+
+
N
O
N
80 oC, 4 h
N
CHO
Hetero
N
HN
O
- metal-free one pot synthesis
- C-N bond
- good yields
- readily available starting materials
- efficient and mildconditions
- evaluation of antimicrobial activity
Hetero
10 examples
up to 23% yield
13 examples
up to 78% yield
23