Synthesis and antimicrobial activity of dithiocarbamates of ω-Substituted (2-naphthyloxy)alkanes

Article abstract of DOI:10.14233/ajchem.2019.22090

A series of dithiocarbamates of ω-substituted (2-naphthyloxy) alkanes was developed through condensation of 2-(2-chloro-alkoxy)-naphthalene to various kinds of aliphatic, aromatic, alicyclic, heterocyclic primary and secondary amines employing benzyl trimethyl ammonium hydroxide in catalytic quantity (Triton-B/CS2 system) afforded desired products in high yields (82-98 %). The complete series of synthesized compounds (4-48) were evaluated for antimicrobial activity through microdilution method using various bacterial and fungal strains. The antifungal and antibacterial values were estimated as MIC values. Fluconazole and ciprofloxacin [16 to 0.03 μg/ mL] were used as the standard antifungal and antibacterial drug, respectively. Out of series of evaluated compounds, some of these compounds such as compounds 28, 29, 30, 31, 32, 33 have displayed maximum potency which is comparable to standard drugs.

Full text of DOI:10.14233/ajchem.2019.22090

Asian Journal of Chemistry; Vol. 31, No. 10 (2019), 2201-2210
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2019.22090
Synthesis and Antimicrobial Activity of Dithiocarbamates of
ω-Substituted (2-naphthyloxy)alkanes
1,*
2
1
3
SADAF ZAIDI , DEVDUTT CHATURVEDI , MRIDULA SAXENA and RICHA SRIVASTAVA
1Department ofApplied Chemistry, Amity School ofApplied Sciences, Amity University Uttar Pradesh, Lucknow Campus, Lucknow-226028, India
2Department of Chemistry, School of Physical & Material Sciences, Mahatma Gandhi Central University, Motihari-845401, India
3Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Campus, Lucknow-226028, India
*Corresponding author: E-mail: sadaf.zaidi00@gmail.com
Received: 22 March 2019;
Accepted: 30 April 2019;
Published online: 30 August 2019;
AJC-19523
A series of dithiocarbamates of ω-substituted (2-naphthyloxy) alkanes was developed through condensation of 2-(2-chloro-alkoxy)-
naphthalene to various kinds of aliphatic, aromatic, alicyclic, heterocyclic primary and secondary amines employing benzyl trimethyl
ammonium hydroxide in catalytic quantity (Triton-B/CS2 system) afforded desired products in high yields (82-98 %). The complete
series of synthesized compounds (4-48) were evaluated for antimicrobial activity through microdilution method using various bacterial
and fungal strains. The antifungal and antibacterial values were estimated as MIC values. Fluconazole and ciprofloxacin [16 to 0.03 µg/
mL] were used as the standard antifungal and antibacterial drug, respectively. Out of series of evaluated compounds, some of these
compounds such as compounds 28, 29, 30, 31, 32, 33 have displayed maximum potency which is comparable to standard drugs.
Keywords: Dithiocarbamates, Antimicrobial, Amines.
thiones [37], benzimidazole [38], carbamate [39], pyran [40]
and flavonoids [41], etc.Apart from above mentioned activities,
dithiocarba-mates of various imidazole [42], brassinin [43],
rhodanine [44], quinoline [45], metal complexes [46], ammonium
salts [47], etc. derivative have emerged as potent antimicrobial
agents. As our group is working in drug discovery through
design and synthesis of novel class of natural/semi-synthetic/
synthetic molecules especially molecules like carbamates, dithio-
carbamates, dithiocarbazates, etc. Keeping in view the importance
of dithiocarbamates and its derivatives, we became interested
in investigating various structurally diverse biologically potent
compounds.
INTRODUCTION
Dithiocarbamates have always received the attention of
the researchers round the world because of its wide utility in
areas such as pharmaceuticals [1-4], intermediate product in
organic synthesis [5], for the sheilding of amino groups in
peptide chemistry [6,7] and as linking agents in combinatorial
chemistry [8-10]. Organic dithiocarbamates have been exten-
sively used as intermediate for the synthesis of structurally
diverse synthetic intermediates/molecules of biological signifi-
cance like antimalarial [11], anticholinergic [12], antimicrobial
[13], antimitotic [14], antitubercular [15], antifungal [16],
anticancer [17], antioxidant [18], antiprotozoal [19], antile-
prosy [20], antifolates [21], antitubulin [22], antialzheimer
[23], anti-HIV [24], antipoliferative [25] and anticontraceptives
[26] active agents. As a useful synthon organic dithiocarba-
mates have been extensively used for the synthesis of structurally
diverse biological potent synthetic intermediates/molecules
like isothiocyanates [27], thiourea [28], cynamide [29], dithio-
benzophene [30],glycosides [31], β-sulphonamides [32], amide
[33], dicarboxylates [34], thiadizoles [35], dithiolanes [36],
Considering the potency of dithiocarbamates as antimicro-
bial agents, we became interested to investigate the antimicro-
bial activity of dithiocarbamates of ω-substituted (2-naphthyloxy)
alkanes (Prototype I).
EXPERIMENTAL
Procedure for ω-substituted 2-naphthyloxy haloalkanes
(3): Measured amount of β-naphthol (1) was taken in dry acetone
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2202 Zaidi et al.
Asian J. Chem.
S
saline and their density was adjusted to 0.5 McFarland. The
bacterial cultures were diluted and added in 100 mL volume
to a final inoculum of 1 × 105 CFU/mL. For fungal cultures
1 × 103 CFU/mL was used. The plates were incubated at 37 °C
for 24 h for bacterial cultures and 48 h for fungal cultures. The
plates were read visually and the minimum concentration of
the compounds showing no turbidity was recorded as MIC.
All the chemicals used were obtained from Merck,Aldrich
and Fluka chemical companies. Reactions were carried out in
nitrogenous atmosphere. The structural analysis of compound
was done as IR spectra (4000-200 cm-1) on Bomem MB-104–
FTIR spectrophotometer where as NMRs were scanned on
AC-300F, NMR (300 MHz), instrument using CDCl3 andsome
other deutrated solvents and TMS as internal standard.
Elemental analysis were made by Carlo-Erba EA 1110-CNNO-
S analyzer and the obtained values were in accordance with
calculated values.
General procedure for the preparation of ω-naphthyloxy
halo alkanes (3a-c) involves refluxing of mixture of β-naphthol
(1) (20 g, 0.14 mol), anhydrous K2CO3 (100 g, in excess) and
bromochloroalkane 2 (0.14 mol) in dry acetone (200 mL) for
12-15 h. Reaction mixture was filtered and filtrate was concen-
trated to get oily compound, which was crystallized with
benzene-hexane to give the colourless crystals of pure desired
compound (Scheme-I) [48].
2-(2-Naphthyloxy)-1-chloroethane (3a): Yield: 27.4 g
(96 %); m.p.: 94 °C; IR (KBr, νmax, cm-1): 1455 (Ar), 1507
(Ar), 1586 (Ar), 2878 (CH), 2927 (CH); 1H NMR (400 MHz,
CDCl3): δ = 3.82 (t, 2H, CH2Cl), 4.24 (t, 2H, OCH2), 6.97–
7.65 (m, 7H, Ar–H); 13C NMR (100 MHz, CDCl3): δ = 45.2,
75.2, 105.7, 118.5, 123.7, 126.5, 129.6, 134.4, 157.6 ppm;
Mass (EIMS): m/z = 206;Analysis: C12H11OCl, Calcd. (%): C,
69.74; H, 5.36; Obsd. (%): C, 70.04, H, 5.66.
3-(2-Naphthyloxy)-1-chloropropane (3b): Yield: 29.6
g (97 %); m.p.: 98 °C; IR (KBr, νmax, cm-1): 1462 (Ar), 1511
(Ar), 1595 (Ar), 2856 (CH), 2942 (CH); 1H NMR (400 MHz,
CDCl3): δ = 2.26–2.34 (m, 2H, CH2), 3.84 (t, 2H, CH2Cl),
4.24 (t, 2H, OCH2), 7.12–7.75 (m, 7H, Ar–H) ppm; Mass
(EIMS): m/z = 220;Analysis: C13H13OCl, Calcd. (%): C, 70.75;
H, 5.94; Obsd. (%): C, 70.79; H, 6.21.
O
R1
R2
S
n
N
Prototype I (n = 1, 2 & 3; Compounds 4-48)
and anhyd. K2CO3 (10 eqv.) was added in it. To this, 1-bromo-
3-chloro propane (2) was added (2.5 eqv.) and then the reaction
was refluxed for 12-15 h. The continuous monitoring of progress
of reaction was done by TLC which indicates the appearance
of less polar new spot. The filtrate of reaction mixture was
concentrated, extracted thrice with ethyl acetate. After sepa-
ration the organic layer was dried over anhydrous Na2SO4 affor-
ded the corresponding compound 3. Compound 3 was confir-
med by various spectroscopic and analytical techniques.
Procedure for synthesis of dithiocarbamates of
Prototype I (4-48): Measured amount of desired amine was
dissolved in dry DMSO. To this, measured amount of CS2 and
Triton-B were added drop by drop and the reaction was allowed
to stir for 15 min. After adding compound 3 to the reaction
mixture and the reaction was stirred for about 20-40 min.
Monitoring of reaction progress was done by TLC. Triple
extraction of reaction mixture was done with ethyl acetate once
the reaction was complete. The organic layer was separated,
dried over anhydrous Na2SO4 afforded the final product that
is, dithiocarbamates of prototype I (compounds 4-48).
Biological activities: The antibacterial and antifungal
activities of the ω-substituted (2-naphthyloxy) alkanes against
bacterial strains (Staphylococcus aureusATCC 29313, Methi-
cillin resistant Staphylococcus aureus), two Gram-negative
strains (Escherichia coliATCC 25922, Pseudomonas aeruginosa
ATCC 27853), two yeast strains (Candida albicans ATCC
22019, S. schencki) and two filamentous fungi (Aspergillus
fumigatus LSI-II, Aspergillus nigerATCC 16404) was perfor-
med by using microdilution method. Antibacterial tests were
performed using Muller Hinton Broth which was buffered to
pH 7.0. The antifungal testing was performed using RPMI
1640 with L-glutamine buffered to pH 7.0. It was supplemented
with 0.165 M 3-(N-morpholino) propanesulfonic acid (MOPS)
[Sigma-Aldrich]. The stock solution of the compounds was
prepared using DMSO. The minimum inhibitory concentration
(MIC) of the compounds was determined by serial 2 fold dilu-
ting the oils in the abovementioned media in 100 mL volume
in a 96 well U bottom microtitre plate. The final concentrations
of compound ranged from 128 to 0.25 µg/mL. Flucanazone
and ciprofloxacin [16 to 0.03 µg/mL] (Sigma-Aldrich) were
used as standard antifungal and antibacterial agents respec-
tively. The bacterial and fungal suspension of the overnight
grown bacterial and fungal was prepared in sterile normal
4-(2-Naphthyloxy)-1-chlorobutane (3c): Yield: 34 g (98
%); m.p.: 112 °C; IR (KBr, νmax, cm-1): 1463 (Ar), 1512 (Ar),
1
1598 (Ar), 2886 (CH), 2942 (CH); H NMR (400 MHz,
CDCl3): δ = 2.15–2.22 (m, 4H, CH2CH2), 3.77 (t, 2H, CH2Cl),
4.25 (t, 2H, OCH2), 7.13–7.76 (m, 7H, Ar– H) ppm; Mass
(EIMS): m/z = 234;Analysis: C14H15OCl, Calcd. (%): C, 70.72;
H, 5.92; Obsd. (%): C, 70.78; H, 6.20.
Procedure for the preparation of dithiocarbamates of
ω-substituted (2-naphthyloxy) alkanes: A mixture of desired
OH
O
Anhyd. K2CO3, dry acetone
Reflux, 12-15h,
Br
Cl
n
Cl
+
n
upto 98% yield
3
2
1
3a n = 1
3b n = 2
3c n = 3
Scheme-I

Vol. 31, No. 10 (2019)
Synthesis and Antimicrobial Activity of Dithiocarbamates of ω-Substituted (2-naphthyloxy)alkanes 2203
amine (0.6 mL, 5 mmol) and carbon disulphide solution (3 mL,
in excess) was taken in dry DMSO (35 mL). Triton-B (0.9 mL,
4 mmol) was added in it and the reaction mixture was stirred
at room temperature for 1 h. Now 2-(2-naphthyloxy)-1-chloro-
alkane (0.5 g, 2 mmol) was added in it and reaction was continued
till its completion (2 h) as checked by TLC. Reaction mixture
was poured into distilled water (50 mL) and three-time extrac-
tion was done with ethyl acetate. After separation of organic
layer, it was dried over anhydrous sodium sulphate and then
concentrated to get dithiocarbamate of ω-substituted (2-naph-
thyloxy) alkanes. This compound was obtained as yellow solid
(Scheme-II).
(Ar), 2875 (CH), 2936 (CH), 3394 (NH); 1H NMR (CDCl3): δ
= 0.92-0.95 (t, 3H, CH3), 1.27-1.29 (m, 4H, CH2CH2CH2CH3
of hexyl group), 1.31-1.35 (m, 2H, CH2CH3 of hexyl group),
1.52-1.56 (m, 2H, CH2.CH2.CH3 of hexyl group), 2.0 (bs, H,
NH), 2.36-2.40 (m, 2H, naphthyl-O-CH2CH2CH2-S-C=S),
2.63-2.65 (m, 2H, NHCH2), 3.24-3.29 (t, 2H, CH2-S-C=S),
4.68-4.73 (t, 2H, CH2-O-naphthyl), 6.96-7.62 (m, 7H, Ar-H
of naphthyloxy); Mass: m/e 347.14; Analysis: C19H25NOS2,
Calcd. (%): C, 66.44, H 7.53, N, 3.87, 18.45 %: O, 4.60. Obsd.
(%): C, 65.66, H, 7.25, N, 4.03, S, 18.45 %: O, 4.60.
Hexyl-dithiocarbamic acid-3-(naphthalene-2-yloxy)-
propyl ester (8):Yield: 0.8 g (96.4 %); m.p.: 119 °C; IR (KBr,
Butyl-dithiocarbamic acid-2-(naphthalen-2-yloxy)ethyl
ν
max, cm-1): 662 (C-S), 1116 (C=S), 1475 (Ar), 1514 (Ar), 1602
ester (4): Yield: 0.73 g (93.5 %); m.p.: 106 °C; IR (KBr, νmax
,
(Ar), 2875 (CH), 2936 (CH), 3394 (NH); 1H NMR (CDCl3): δ
= 0.92-0.94 (t, 3H, CH3), 1.27-1.29 (m, 4H, CH2CH2CH2CH3
of hexyl group), 1.31-1.35 (m, 2H, CH2CH3 of hexyl group),
1.52-1.58 (m, 2H, CH2.CH2.CH3 of hexyl group), 2.0 (bs, H,
NH), 2.34-2.42 (m, 2H, naphthyl-O-CH2CH2CH2-S-C=S),
2.63-2.66 (m, 2H, NHCH2), 2.81-2.86 (t, 2H, CH2-S-C=S),
4.02-4.05 (t, 2H, CH2-O-naphthyl), 6.97-7.64 (m, 7H, Ar-H
of naphthyloxy); Mass: m/e 361;Analysis: C20H27NOS2, Calcd.
(%): C, 66.44, H 7.53, N, 3.87, Obsd. (%): C, 66.75, H, 7.38,
N, 3.71.
cm-1): 661 (C-S), 1114 (C=S), 1454 (Ar), 1511 (Ar), 1612
(Ar), 2864 (CH), 2936 (CH), 3390 (NH); 1H NMR (CDCl3): δ
= 0.92-0.96 (t, 3H, CH3), 1.30-1.34 (m, 2H, CH2CH3), 1.53-
1.56 (m, 2H, CH2.CH2.CH3), 2.0 (bs, H, NH), 2.62-2.64 (m,
2H, NHCH2), 3.28-3.32 (t, 2H, CH2-S-C=S), 4.71-4.74 (t, 2H,
CH2-O-naphthyl), 6.97-7.64 (m, 7H, Ar-H of naphthyloxy);
Mass: m/e 319; Analysis: C17H21NOS2, Calcd. (%): C, 63.91,
H 6.63, N, 4.38; Obsd. (%): C, 64.19, H, 6.49, N, 4.24.
Butyl-dithiocarbamic acid-3-(naphthalene-2-yloxy)-
propyl ester (5): Yield: 0.73 g (93.5 %); m.p.: 106 °C; IR
(KBr, νmax, cm-1): 661 (C-S), 1115 (C=S), 1454 (Ar), 1511
(Ar), 1610 (Ar), 2864 (CH), 2935 (CH), 3390 (NH); 1H NMR
(CDCl3): δ = 0.93-0.96 (t, 3H, CH3), 1.33-1.35 (m, 2H,
CH2CH3), 1.53-1.55 (m, 2H, CH2.CH2.CH3), 2.0 (bs, H, NH),
2.62-2.65 (m, 2H, NHCH2), 2.84-2.86 (t, 2H, CH2-S-C=S),
2.35-2.39 (m, 2H, CH2CH2CH2) 4.01-4.05 (t, 2H, CH2-O-
naphthyl), 6.96-7.62 (m, 7H, Ar-H of naphthyloxy); Mass:
m/e 333; Analysis: C18H23NOS2, Calcd. (%): C, 65.91, H 6.83,
N, 4.38, S, 19.15, Obsd. (%): C, 65.82, H, 6.95, N, 4.20, S,
19.23 %: O, 4.80.
Hexyl-dithiocarbamic acid-4-(naphthalene-2-yloxy)-
butyl ester (9): Yield: 0.72 g (98 %); m.p.: 129 °C; IR (KBr,
ν
max, cm-1): 669 (C-S), 1116 (C=S), 1475 (Ar), 1514 (Ar), 1610
(Ar), 2875 (CH), 2936 (CH), 3410 (NH); 1H NMR (CDCl3): δ
= 0.92-0.96 (t, 3H, CH3), 1.25-1.29 (m, 4H, CH2CH2CH2CH3
of hexyl group), 1.30-1.34 (m, 2H, CH2CH3 of hexyl group),
1.53-1.56 (m, 2H, CH2CH2CH2.CH2.CH3 of hexyl group), 1.71-
1.73 (m, 2H, naphthyl-O-CH2CH2), 1.94-1.96 (m, 2H, S-
CH2CH2), 2.0 (bs, H, NH), 2.62-2.64 (m, 2H, NHCH2), 2.82-
2.86 (t, 2H, CH2-S-C=S), 4.02-4.06 (t, 2H, CH2-O-naphthyl),
6.95-7.62 (m, 7H, Ar-H of naphthyloxy); Mass: m/e 375;
Analysis: C21H29NOS2, Calcd. (%): C, 67.15, H 7.78, N, 3.73,
Obsd. (%): C, 67.59, H, 7.56, N, 3.51.
Butyl-dithiocarbamic acid-4-(naphthalene-2-yloxy)-
butyl ester (6): Yield: 0.73 g (93.5 %); m.p.: 106 °C; IR (KBr,
ν
max, cm-1): 661 (C-S), 1114 (C=S), 1454 (Ar), 1511 (Ar), 1612
Octyl-dithiocarbamic acid-2-(naphthalen-2-yloxy)ethyl
ester (10): Yield: 0.85 g, (96.2 %); m.p.: 172 °C; IR (KBr,
(Ar), 2864 (CH), 2936 (CH), 3390 (NH); 1H NMR (CDCl3): δ
= 0.93-0.96 (t, 3H, CH3), 1.33-1.35 (m, 2H, CH2CH3), 1.53-
1.55 (m, 2H, CH2.CH2.CH3), 2.0 (bs, H, NH), 2.62-2.66 (m,
2H, NHCH2), 2.85-2.87 (t, 2H, CH2-S-C=S), 1.92-1.96 (m,
2H, CH2CH2CH2), 1.68-1.71 (m, 2H, CH2CH2CH2), 4.00-4.03
(t, 2H, CH2-O-naphthyl), 6.96-7.62 (m, 7H, Ar-H of naph-
thyloxy); Mass: m/e 347.14; Analysis: C19H25NOS2, Calcd. (%):
C, 65.60, H 7.22, N, 4.58; S, 18.42 %: O, 4.58. Obsd. (%): C,
65.66, H, 7.25, N, 4.60, S, 18.45 %: O, 4.60.
ν
max, cm-1): 667 (C-S), 1120 (C=S), 1475 (Ar), 1521 (Ar), 1612
(Ar), 2886 (CH), 2941 (CH), 3399 (NH); 1H NMR (CDCl3): δ
= 0.92-0.94 (t, 3H, CH3), 1.27-1.29 (m, 8H, CH2CH2CH2CH2
CH2CH3 of octyl group), 1.32-1.34 (m, 2H, CH2CH3 of octyl
group), 1.53-1.56 (m, 2H, CH2CH2N of n-octyl group), 2.0
(bs, H, NH), 2.62-2.64 (m, 2H, NHCH2), 3.25-3.29 (t, 2H,
CH2-S-C=S), 4.01-4.04 (t, 2H, CH2-O-naphthyl), 6.95-7.62
(m, 7H, Ar-H of naphthyloxy); Mass: m/e 375.17; Analysis:
C21H29NOS2, Calcd. (%): C, 67.15, H, 7.78, N, 3.73; O, 4.22;
S, 17.04.Obsd. (%): C, 67.15, H, 7.78, N, 3.73, O, 4.26; S,
17.07.
Hexyl-dithiocarbamic acid-2-(naphthalen-2-yloxy)ethyl
ester (7): Yield: 0.8 g (96.4 %); m.p.: 119 °C; IR (KBr, νmax
,
cm-1): 665 (C-S), 1116 (C=S), 1475 (Ar), 1514 (Ar), 1602
S
O
R1
R2
O
CS2, Amines
S
Cl
n
n
N
Triton-B
DMSO 20-30 min.
n = 1, 2 & 3
Prototype I (Comp. no. 4-48)
3
Scheme-II

2204 Zaidi et al.
Asian J. Chem.
Octyl-dithiocarbamic acid-3-(naphthalene-2-yloxy)-
2.87 (t, 2H, CH2-S-C=S), 1.93-1.95 (m, 2H, CH2CH2CH2),
1.67-1.71 (m, 2H, CH2CH2CH2),4.68-4.71 (t, 2H, CH2-O-
naphthyl), 6.97-7.64 (m, 7H, Ar-H of naphthyloxy); Mass: m/e
431.70; Analysis: C25H37NOS2, Calcd. (%): C, 69.52, H 8.63,
N, 3.21, O, 3.70, S, 14.82. Obsd. (%): C, 69.56, H, 8.64, N,
3.24, O, 3.71, S, 14.86.
Pyrrolidine-dithiocarbamic acid-2-(naphthalen-2-
yloxy)ethyl ester (16): Yield: 0.62 g (80.8 %); m.p.: 79 °C;
IR (KBr, νmax, cm-1): 657 (C-S), 1106 (C=S), 1454 (Ar), 1502
(Ar), 1600 (Ar), 2863 (CH), 2925 (CH); 1H NMR (CDCl3): δ
= 1.58-1.60 (m, 4H, CH2 of pyrrolidine ring), 2.8 (t, 4H, CH2N
of pyrrolidine ring (2H, CH2-S-C=S), 4.71-4.73 (t, 2H, CH2-
O-naphthyl), 6.96-7.62 (m, 7H, Ar-H of naphthyloxy); Mass:
m/e 317;Analysis: C17H19NOS2, Calcd. (%): C, 64.32, H, 6.03,
N, 4.41, Obsd. (%): C, 63.85, H, 6.29, N, 4.64.
Pyrrolidine-dithiocarbamic acid-3-(naphthalen-2-
yloxy)propyl ester (17): Yield: 0.63 g (83.2 %); m.p.: 86 °C;
IR (KBr, νmax, cm-1): 672 (C-S), 1124 (C=S), 1475 (Ar), 1524
(Ar), 1605 (Ar), 2885 (CH), 2926 (CH); 1H NMR (CDCl3): δ
= 1.57-1.61 (m, 4H, CH2 of pyrrolidine ring), 2.35-2.38 (m,
2H, naphthyl-O-CH2CH2CH2-S-C=S), 2.8 (t, 4H, CH2N of
pyrrolidine ring), 2.82-2.86 (t, 2H, CH2-S-C=S), 4.02-4.04 (t,
2H, CH2-O-naphthyl), 6.96-7.62 (m, 7H,Ar-H of naphthyloxy);
Mass: m/e 331; Analysis: C18H21NOS2, Calcd. (%): C, 65.22,
H, 6.39, N, 4.23, Obsd. (%): C, 65.63, H, 6.12, N, 4.01.
Pyrrolidine-dithiocarbamic acid-4-(naphthalen-2-
yloxy)butyl ester (18): Yield: 0.64 g (86.5 %); m.p.: 95 °C;
IR (KBr, νmax, cm-1): 679 (C-S), 1125 (C=S), 1484 (Ar), 1525
(Ar), 1610 (Ar), 2885 (CH), 2947 (CH); 1H NMR (CDCl3): δ
= 1.56-1.60 (m, 4H, CH2 of pyrrolidine ring), 1.71-1.72 (m,
2H, naphthyl-O-CH2CH2), 1.95-1.98 (m, 2H, S-CH2CH2), 2.8
(t, 4H, CH2N of pyrrolidine ring), 2.84-2.88 (t, 2H, CH2-S-
C=S), 4.02-4.05 (t, 2H, CH2-O-naphthyl), 6.97-7.64 (m, 7H,
Ar-H of naphthyloxy); Mass: m/e 345;Analysis: C19H23NOS2,
Calcd. (%): C, 66.09, H, 6.57, N, 4.15, Obsd. (%): C, 66.57,
H, 6.32, N, 3.86.
Piperidine-1-dithiocarbamic acid-2-(naphthalen-2-
yloxy)ethyl ester (19): Yield: 0.66 g (82.5 %); m.p.: 89 °C;
IR (KBr, νmax, cm-1): 660 (C-S), 1110 (C=S), 1461 (Ar), 1509
(Ar), 1605 (Ar), 2859 (CH), 2926 (CH); 1H NMR (CDCl3): δ
= 1.48-1.50 (m, 6H, CH2 of piperidine ring), 2.7 (t, 4H, CH2N
of piperidine ring), 3.28-3.30 (t, 2H, CH2-S-C=S), 4.71-4.73
(t, 2H, CH2-O-naphthyl), 6.95-7.62 (m, 7H, Ar-H of naph-
thyloxy); Mass: m/e 331; Analysis: C18H21NOS2, Calcd. (%):
C, 65.22, H 6.39, N, 4.23, Obsd. (%): C, 65.73, H, 6.13, N,
3.98.
propyl ester (11): Yield: 0.85 g, (96.2 %); m.p.: 172 °C; IR
(KBr, νmax, cm-1): 667 (C-S), 1120 (C=S), 1472 (Ar), 1521
(Ar), 1612 (Ar), 2884 (CH), 2941 (CH), 3399 (NH); 1H NMR
(CDCl3): δ = 0.92-0.94 (t, 3H, CH3), 1.27-1.29 (m, 8H,
CH2CH2CH2CH2 CH2CH3 of octyl group), 1.30-1.32 (m, 2H,
CH2CH3 of octyl group), 1.53-1.56 (m, 2H, CH2CH2N of n-
octyl group), 2.0 (bs, H, NH), 2.38-2.42 (m, 2H, naphthyl-O-
CH2CH2CH2-S-C=S), 2.63-2.66 (m, 2H, NHCH2), 2.83-2.87
(t, 2H, CH2-S-C=S), 4.01-4.04 (t, 2H, CH2-O-naphthyl), 6.98-
7.66 (m, 7H, Ar-H of naphthyloxy); Mass: m/e 389; Analysis:
C22H31NOS2, Calcd. (%): C, 67.62, H, 8.02, N, 3.59; Obsd.
(%): C, 67.89, H, 7.90, N, 3.44.
Octyl-dithiocarbamic acid-4-(naphthalene-2-yloxy)-
butyl ester (12): Yield: 0.86 g (94 %); m.p.: 156 °C; IR (KBr,
ν
max, cm-1):664(C-S), 1108(C=S), 1463(Ar), 1514(Ar), 1602 (Ar),
2862 (CH), 2926 (CH), 3392 (NH); 1H NMR (CDCl3): δ = 0.93-
0.95 (t, 3H, CH3), 1.27-1.29 (m, 8H, CH2CH2CH2CH2CH2CH3
of octyl group), 1.30-1.34 (m, 2H, CH2CH3 of octyl group),
1.52-1.57 (m, 2H, CH2.CH2.N), 2.0 (bs, H, NH), 2.63-2.67
(m, 2H, NHCH2), 3.26-3.32 (t, 2H, CH2-S-C=S), 4.71-4.74 (t,
2H, CH2-O-naphthyl), 6.96-7.62 (m, 7H, Ar-H of naphthy-
loxy); Mass: m/e 375; Analysis: C21H29NOS2, Calcd. (%): C,
67.15, H 7.78, N, 3.73, Obsd. (%): C, 67.54, H, 7.56, N, 3.56.
Decyl-dithiocarbamic acid-2-(naphthalen-2-yloxy)ethyl
ester (13): Yield: 0.86 g (94 %); m.p.: 156 °C; IR (KBr, νmax
,
cm-1): 663 (C-S), 1108 (C=S), 1465 (Ar), 1511 (Ar), 1605
(Ar), 2862 (CH), 2926 (CH), 3392 (NH); 1H NMR (CDCl3): δ
= 0.92-0.94 (t, 3H, CH3), 1.27-1.29 (m, 10H, CH2CH2CH2CH2
CH2CH2CH2CH3 of decyl group), 1.31-1.35 (m, 2H, CH2CH3
of decyl group), 1.53-1.56 (m, 2H, CH2CH2N of n-decyl
group), 2.01 (bs, H, NH), 2.63-2.65 (m, 2H, NHCH2), 3.25-
3.29 (t, 2H, CH2-S-C=S), 4.68-4.71 (t, 2H, CH2-O-naphthyl),
6.97-7.64 (m, 7H, Ar-H of naphthyloxy); Mass: m/e 403.25;
Analysis: C23H33NOS2, Calcd. (%): C, 68.40, H 8.20, N, 3.90,
O, 3.92, S, 15.86; Obsd. (%): C, 68.44, H, 8.24, N, 3.96. O,
3.96, S, 15.89.
Decyl-dithiocarbamic acid-3-(naphthalene-2-yloxy)-
propyl ester (14): Yield: 0.86 g (94 %); m.p.: 156 °C; IR
(KBr, νmax, cm-1): 664 (C-S), 1109 (C=S), 1462 (Ar), 1513
(Ar), 1602 (Ar), 2863 (CH), 2925 (CH), 3392 (NH); 1H NMR
(CDCl3): δ = 0.92-0.95 (t, 3H, CH3), 1.27-1.29 (m, 10H,
CH2CH2CH2CH2 CH2CH2CH2CH3 of decyl group), 1.31-1.35
(m, 2H, CH2CH3 of decyl group), 1.53-1.56 (m, 2H, CH2CH2N
of n-decyl group), 2.0 (bs, H, NH), 2.62-2.66 (m, 2H, NHCH2),
2.84-2.87 (t, 2H, CH2-S-C=S), 2.34-2.38 (m, 2H, CH2CH2),
4.68-4.71 (t, 2H, CH2-O-naphthyl), 6.96-7.62 (m, 7H, Ar-H
of naphthyloxy); Mass: m/e 417.67; Analysis: C24H35NOS2,
Calcd. (%): C, 69, H 8.40, N, 3.35, O, 3.80, S, 15.31. O, 3.83,
S, 15.35. Obsd. (%): C, 69.02, H, 8.45, N, 3.35, O, 3.83, S, 15.35.
Decyl-dithiocarbamic acid-4-(naphthalene-2-yloxy)-
butyl ester (15): Yield: 0.86 g (94 %); m.p.: 156 °C; IR (KBr,
Piperidine-1-dithiocarbamic acid-3-(naphthalen-2-
yloxy)propyl ester (20):Yield: 0.66 g (82.5 %); m.p.: 89 °C;
IR (KBr, νmax, cm-1): 662 (C-S), 1112 (C=S), 1461 (Ar), 1509
(Ar), 1605 (Ar), 2859 (CH), 2927 (CH); 1H NMR (CDCl3): δ
= 1.48-1.50 (m, 6H, CH2 of piperidine ring), 2.7 (t, 4H, CH2N
of piperidine ring), 2.82-2.86 (t, 2H, CH2-S-C=S), 2.35-2.38
(m, 2H, CH2CH2), 4.01-4.04 (t, 2H, CH2-O-naphthyl), 6.95-
7.62 (m, 7H, Ar-H of naphthyloxy); Mass: m/e 392.54;
Analysis: C19H24N2O2S3, Calcd. (%): C, 58.22, H 6.20, N, 7.23,
Obsd. (%): C, 58.14.73, H, 6.16, N, 7.14, O, 12.23, S, 16.13.
Piperidine-1-dithiocarbamic acid-4-(naphthalen-2-
yloxy)butyl ester (21): Yield: 0.66 g (82.5 %); m.p.: 89 °C;
ν
max, cm-1): 663 (C-S), 1107 (C=S), 1462 (Ar), 1510 (Ar), 1606
(Ar), 2865 (CH), 2926 (CH), 3392 (NH); 1H NMR (CDCl3): δ
= 0.92-0.94 (t, 3H, CH3), 1.27-1.29 (m, 10H, CH2CH2CH2CH2
CH2CH2CH2CH3 of decyl group), 1.30-1.34 (m, 2H, CH2CH3
of decyl group), 1.52-1.58 (m, 2H, CH2CH2N of n-decyl
group), 2.0 (bs, H, NH), 2.62-2.66 (m, 2H, NHCH2), 2.84-

Vol. 31, No. 10 (2019)
Synthesis and Antimicrobial Activity of Dithiocarbamates of ω-Substituted (2-naphthyloxy)alkanes 2205
IR (KBr, νmax, cm-1): 660 (C-S), 1110 (C=S), 1461 (Ar), 1509
(Ar), 1605 (Ar), 2859 (CH), 2925 (CH); 1H NMR (CDCl3): δ
= 1.48-1.50 (m, 6H, CH2 of piperidine ring), 2.7 (t, 4H, CH2N
of piperidine ring), 2.83-2.86 (t, 2H, CH2-S-C=S), 1.92-1.96
(m, 2H, CH2CH2), 1.68-1.71 (m, 2H, CH2CH2), 4.00-4.02 (t,
2H, CH2-O-naphthyl), 6.96-7.65 (m, 7H, Ar-H of naphthy-
loxy); Mass: m/e 406.56;Analysis: C20H26N2O3S2, Calcd. (%):
C, 59.12, H 6.49, N, 6.82, O, 11.82, S, 15.75. Obsd. (%): C,
59.08, H, 6.45, N, 6.89, O, 11.89, S, 15.79.
4-Methyl-piperazine-dithiocarbamic acid-2-(naphthalen-
2-yloxy)ethyl ester (22): Yield: 0.66 g (82.5 %); m.p.: 89 °C;
IR (KBr, νmax, cm-1): 662 (C-S), 1112 (C=S), 1461 (Ar), 1509
(Ar), 1605 (Ar), 2859 (CH), 2926 (CH); 1H NMR (CDCl3): δ
= 2.24-2.27 (s, 3H, CH3 of methyl piperazine ring), 2.44-2.48
(t, CH2N of piperazine ring), 2.62-2.65 (t, CH2N of piperazine
ring), 2.0 (bs, H, NH), 3.25-3.29 (t, 2H, CH2-S-C=S), 4.68-
4.71 (t, 2H, CH2-O-naphthyl), 6.96-7.65 (m, 7H, Ar-H of
naphthyloxy); Mass: m/e 361; Analysis: C18H23N3OS2, Calcd.
(%): C, 59.84, H 6.39, N, 11.60, O, 4.40, S, 17.72 % Obsd.
(%): C, 59.80, H, 6.41, N, 11.62 % O, 4.43, S, 17.74.
(Ar), 1605 (Ar), 2859 (CH), 2926 (CH); 1H NMR (CDCl3): δ
= 3.62-3.67 (t, 2H, CH2 of morphaline ring), 2.34-2.37 (t, CH2N
of morphaline ring), 2.35-2.40 (s, CH2-S-C=S), 1.95-1.99 (m,
4H, CH2CH2), 4.68-4.71 (t, 2H, CH2-O-naphthyl), 6.96-7.65
(m, 7H, Ar-H of naphthyloxy); Mass: m/e 396.52; Analysis:
C18H24N2O4S2, Calcd. (%): C, 45.50, H 6.09, N, 7.10, O, 16.10,
S, 16.15. Obsd. (%): C, 45.52, H, 6.10, N, 7.06 % O, 16.14, S,
16.17.
Morpholine 4-dithiocarbamic acid-4-(naphthalen-2-
yloxy)butyl ester (27): Yield: 0.66 g (82.5 %); m.p.: 89 °C;
IR (KBr, νmax, cm-1): 660 (C-S), 1110 (C=S), 1461 (Ar), 1509
(Ar), 1605 (Ar), 2859 (CH), 2926 (CH); 1H NMR (CDCl3): δ
= 3.62-3.67 (t, 2H, CH2 of morphaline ring), 2.34-2.37 (t, CH2N
of morphaline ring), 2.35-2.40 (s, CH2SCS), 3.25-3.28 (t, 2H,
CH2-S-C=S), 1.94-1.96 (m, 2H, CH2CH2CH2), 1.68-1.71 (m,
2H, CH2CH2CH2), 4.68-4.71 (t, 2H, CH2-O-naphthyl), 6.96-
7.63 (m, 7H, Ar-H of naphthyloxy); Mass: m/e 410.55;
Analysis: C19H26N2O4S2, Calcd. (%): C, 55.55, H 6.39, N, 6.30,
O, 15.55, S, 15.60. Obsd. (%): C, 55.58, H, 6.35, N, 6.85, O,
15.59, S, 15.62.
4-Methyl-piperazine-dithiocarbamic acid-3-(naphthalen-
2-yloxy)propyl ester (23): Yield: 0.66 g (82.5 %); m.p.: 89
°C; IR (KBr, νmax, cm-1): 660 (C-S), 1110 (C=S), 1461 (Ar),
p-Tolyl-dithiocarbamic acid-2-(naphthalen-2-yloxy)-
ethyl ester (28): Yield: 0.76 g (88.4 %); m.p.: 137 °C; IR (KBr,
ν
max, cm-1): 660 (C-S), 1111 (C=S), 1454 (Ar), 1502 (Ar), 1602
1
1509 (Ar), 1605 (Ar), 2859 (CH), 2926 (CH); H NMR
(Ar), 2851 (CH), 2928 (CH), 3388 (NH); 1H NMR (CDCl3): δ
= 2.34 (s, 3H, CH3), 3.28-3.30 (t, 2H, CH2-S-C=S), 4.0 (bs, H,
NH), 4.70-4.72 (t, 2H, CH2-O-naphthyl), 6.35-7.62 (m, 11H,
Ar-H of naphthyloxy and phenyl ring); Mass: m/e 353;
Analysis: C20H19NOS2, Calcd. (%): C, 67.89, H, 5.45, N, 3.99,
Obsd. (%): C, 67.63, H, 5.58, N, 4.12.
(CDCl3): δ = 2.24-2.27 (s, 3H, CH3 of methyl piperazine ring),
2.44-2.48 (t, CH2N of piperazine ring), 2.62-2.65 (t, CH2N of
piperazine ring), 2.0 (bs, H, NH), 2.84-2.87 (t, 2H, CH2-S-
C=S), 2.34-2.38 (m, 2H, CH2CH2), 4.68-4.71 (t, 2H, CH2-O-
naphthyl), 6.96-7.63 (m, 7H, Ar-H of naphthyloxy); Mass:
m/e 375.55; Analysis: C19H25N3OS2, Calcd. (%): C, 60.72, H
6.69, N, 11.23, O, 4.22, S, 17.05 % Obsd. (%): C, 60.76, H,
6.71, N, 11.19, O, 4.26, S, 17.08.
p-Tolyl-dithiocarbamic acid-3-(naphthalen-2-yloxy)-
propyl ester (29): Yield: 0.76 g (88.4 %); m.p.: 137 °C; IR
(KBr, νmax, cm-1): 662 (C-S), 1111 (C=S), 1454 (Ar), 1502
(Ar), 1601 (Ar), 2851 (CH), 2928 (CH), 3388 (NH); 1H NMR
(CDCl3): δ = 2.34 (s, 3H, CH3), 3.28-3.30 (t, 2H, CH2-S-C=S),
4.0 (bs, H, NH), 2.35-2.40 (s, CH2-S-C=S), 1.95-1.99 (m, 4H,
CH2CH2), 4.68-4.71 (t, 2H, CH2-O-naphthyl), 6.34-7.64 (m,
11H,Ar-H of naphthyloxy and phenyl ring); Mass: m/e 367.53;
Analysis: C21H21NOS2, Calcd. (%): C, 68.60, H, 5.72, N, 3.80,
O, 4.31, S, 17.45 % Obsd. (%): C, 68.63, H, 5.76, N, 3.81 %
O, 4.35, S, 17.45.
4-Methyl-piperazine-dithiocarbamic acid-4-(naphthalen-
2-yloxy)butyl ester (24): Yield: 0.66 g (82.5 %); m.p.: 89 °C;
IR (KBr, νmax, cm-1): 662 (C-S), 1112 (C=S), 1461 (Ar), 1509
(Ar), 1605 (Ar), 2859 (CH), 2925 (CH); 1H NMR (CDCl3): δ
= 2.24-2.27 (s, 3H, CH3 of methyl piperazine ring), 2.44-2.48
(t, CH2N of piperazine ring), 2.62-2.65 (t, CH2N of piperazine
ring), 2.0 (bs, H, NH), 2.84-2.86 (t, 2H, CH2-S-C=S), 1.94-
1.96 (m, 2H, CH2CH2CH2), 1.68-1.71 (m, 2H, CH2CH2CH2),
4.68-4.71 (t, 2H, CH2-O-naphthyl), 6.96-7.62 (m, 7H, Ar-H
of naphthyloxy); Mass: m/e 389.58; Analysis: C20H27N3OS2,
Calcd. (%): C, 61.64, H 6.93, N, 10.73, O, 4.08, S, 16.42 %
Obsd. (%): C, 61.66, H, 6.99, N, 10.79, O, 4.11, S, 16.46.
Morpholine 4-dithiocarbamic acid-2-(naphthalen-2-
yloxy)ethyl ester (25): Yield: 0.66 g (82.5 %); m.p.: 89 °C;
IR (KBr, νmax, cm-1): 660 (C-S), 1110 (C=S), 1461 (Ar), 1509
(Ar), 1605 (Ar), 2859 (CH), 2926 (CH); 1H NMR (CDCl3): δ
= 3.62-3.67 (t, 2H, CH2 of morphaline ring), 2.34-2.37 (t, CH2N
of morphaline ring), 2.35-2.40 (s, CH2SCS), 2.84-2.86 (t, 2H,
CH2-S-C=S), 2.34-2.38 (m, 2H, CH2CH2), 4.68-4.71 (t, 2H,
CH2-O-naphthyl), 6.95-7.62 (m, 7H, Ar-H of naphthyloxy);
Mass: m/e 382.50; Analysis: C17H22N2O4S2, Calcd. (%): C,
53.35, H 5.79, N, 7.30, O, 16.70, S, 16.72 Obsd. (%): C, 53.38,
H, 5.80, N, 7.32, O, 16.73, S, 16.77.
p-Tolyl-dithiocarbamic acid-4-(naphthalen-2-yloxy)-
butyl ester (30): Yield: 0.76 g (88.4 %); m.p.: 137 °C; IR (KBr,
ν
max, cm-1): 662 (C-S), 1111 (C=S), 1454 (Ar), 1502 (Ar), 1601
(Ar), 2851 (CH), 2928 (CH), 3388 (NH); 1H NMR (CDCl3): δ
= 2.34 (s, 3H, CH3), 3.28-3.30 (t, 2H, CH2-S-C=S), 4.0 (bs, H,
NH), 2.35-2.40 (s, CH2SCS), 3.25-3.27 (t, 2H, CH2-S-C=S),
1.94-1.96 (m, 2H, CH2CH2CH2), 1.68-1.71 (m, 2H, CH2CH2CH2),
4.71-4.73 (t, 2H, CH2-O-naphthyl), 6.35-7.63 (m, 11H, Ar-H
of naphthyloxy and phenyl ring); Mass: m/e 381.55;Analysis:
C22H23NOS2, Calcd. (%): C, 69.20, H, 6.06, N, 3.62, O, 4.15,
S, 16.79. Obsd. (%): C, 69.25, H, 6.08, N, 3.67, O, 4.19, S,
16.81.
(4-Methoxy-4-phenyl)dithiocarbamic acid-2-(naphthalen-
2-yloxy)ethyl ester (31): Yield: 0.8 g (89.2 %); m.p.: 117 °C;
IR (KBr, νmax, cm-1): 659 (C-S), 1106 (C=S), 1455 (Ar), 1502
(Ar), 1600 (Ar), 2854 (CH), 2926 (CH), 3389 (NH); 1H NMR
(CDCl3): δ = 3.28-3.30 (t, 2H, CH2-S-C=S), 3.72 (s, 3H,
OCH3), 4.0 (bs, H, NH), 4.70-4.72 (t, 2H, CH2-O-naphthyl),
Morpholine 4-dithiocarbamic acid-3-(naphthalen-2-
yloxy)propyl ester (26): Yield: 0.66 g (82.5 %); m.p.: 89 °C;
IR (KBr, νmax, cm-1): 662 (C-S), 1112 (C=S), 1461 (Ar), 1509

2206 Zaidi et al.
Asian J. Chem.
6.35-7.64 (m, 11H, Ar-H of naphthyloxy and phenyl ring);
Mass: m/e 369; Analysis: C20H19NO2S2, Calcd. (%): C, 65.01,
H, 5.18, N, 3.79, Obsd. (%): C, 65.47, H, 5.03, N, 3.48.
(4-Methoxy-4-phenyl)dithiocarbamic acid-3-(naphthalen-
2-yloxy)propyl ester (32): Yield: 0.82 g (93.8 %); m.p.: 139
°C; IR (KBr, νmax, cm-1): 668 (C-S), 1117 (C=S), 1472 (Ar),
1524 (Ar), 1614 (Ar), 2876 (CH), 2938 (CH), 3396 (NH);
1H NMR (CDCl3): δ = 2.38-2.42 (m, 2H, naphthyl-O-
CH2CH2CH2-S-C=S), 2.84-2.88 (t, 2H, CH2-S-C=S), 3.74 (s,
3H, OCH3), 4.0 (bs, H, NH), 4.02-4.05 (t, 2H, CH2-O-
naphthyl), 6.34-7.65 (m, 11H,Ar-H of naphthyloxy and phenyl
ring); Mass: m/e 383; Analysis: C21H21NO2S2, Calcd. (%): C,
65.76, H 5.52, N, 3.65, Obsd. (%): C, 65.27, H, 5.85, N, 3.81.
(4-Methoxy-4-phenyl)dithiocarbamic acid-4-(naphthalen-
2-yloxy)butyl ester (33): Yield: 0.83 g (94.5 %); m.p.: 126
°C; IR (KBr, νmax, cm-1): 681 (C-S), 1126 (C=S), 1484 (Ar),
1523 (Ar), 1610 (Ar), 2885 (CH), 2936 (CH), 3407 (NH); 1H
NMR (CDCl3): δ = 1.71-1.74 (m, 2H, naphthyl-O-CH2CH2),
1.94-1.96 (m, 2H, S-CH2CH2), 2.01 (bs, H, NH), 2.82-2.86 (t,
2H, CH2-S-C=S), 3.72 (s, 3H, OCH3),3.92-3.94 (d, 2H, CH2
of benzylic proton),4.01-4.04 (t, 2H, CH2-O-naphthyl), 6.65-
7.62 (m, 11H, Ar-H of naphthyloxy and phenyl ring); Mass:
m/e 411; Analysis: C23H25NO2S2, Calcd. (%): C, 67.12, H, 6.12,
N, 3.40, Obsd. (%): C, 67.67, H, 6.40, N, 3.67.
Cyclohexyl-dithiocarbamic acid-2-(naphthalen-2-
yloxy)ethyl ester (34): Yeild: 0.714 g (85.5 %), m.p; 112 °C;
IR (KBr, νmax, cm-1): 658 (C-S), 1103 (C=S), 1454 (Ar), 1502
(Ar), 1600 (Ar), 2851 (CH), 2926 (CH), 3373 (NH); 1H NMR
(CDCl3): δ = 1.41-1.45 (m, 6H,CH2 of cyclohexyl ring), 1.62-
1.64 (m, 4H, CH2 of cyclohexyl ring), 2.0 (bs, H, NH), 2.54-
2.58 (m, H, tertiary H of cyclohexyl ring), 3.26-3.29 (t, 2H,
CH2-S-C=S), 4.71-4.74 (t, 2H, CH2-O-naphthyl), 6.98-7.62
(m, 7H, Ar-H of naphthyloxy); Mass: m/e 345; Analysis:
C19H23NOS2, Calcd. (%): C, 66.05, H, 6.71, N, 4.05, Obsd.
(%): C, 65.65, H, 6.97, N, 4.23.
Cyclohexyl-dithiocarbamic acid-3-(naphthalen-2-
yloxy)propyl ester (35): Yield: 0.714 g (85.5 %); m.p.: 112
°C; IR (KBr, νmax, cm-1): 658 (C-S), 1103 (C=S), 1454 (Ar),
1502 (Ar), 1600 (Ar), 2851 (CH), 2927 (CH), 3373 (NH); 1H
NMR (CDCl3): δ = 1.44-1.48 (m, 6H,CH2 of cyclohexyl ring),
1.63-1.66 (m, 4H, CH2 of cyclohexyl ring), 2.0 (bs, H, NH),
2.54-2.59 (m, H, tertiary H of cyclohexyl ring), 3.28-3.30 (t,
2H, CH2-S-C=S), 4.71-4.73 (t, 2H, CH2-O-naphthyl), 6.95-
7.62 (m, 7H, Ar-H of naphthyloxy); Mass: m/e 345; Analysis:
C19H23NOS2, Calcd. (%): C, 66.05, H, 6.71, N, 4.05, Obsd.
(%): C, 65.65, H, 6.97, N, 4.23.
Cyclohexyl-dithiocarbamic acid-4-(naphthalen-2-
yloxy)butyl ester (36): Yield: 0.75 g (94.5 %); m.p.: 126 °C;
IR (KBr, νmax, cm-1): 668 (C-S), 1121 (C=S), 1469 (Ar), 1523
(Ar), 1617 (Ar), 2879 (CH), 2937 (CH), 3408 (NH); 1H NMR
(CDCl3): δ = 1.42-1.44 (m, 6H, CH2 of cyclohexyl ring), 1.65-
1.68 (m, 4H, CH2 of cylohexyl ring), 1.71-1.73 (m, 2H,
naphthyl-O-CH2CH2), 1.94-1.96 (m, 2H, S-CH2CH2), 2.0 (bs,
H, NH), 2.54-2.57 (m, H, tert. CH of cylohexyl ring), 2.84-
2.88 (t, 2H, CH2-S-C=S), 4.02-4.06 (t, 2H, CH2-O-naphthyl),
6.98-7.62 (m, 7H, Ar-H of naphthyloxy); Mass: m/e 373;
Analysis: C21H27NOS2, Calcd. (%): C, 67.52, H, 7.28, N, 3.75,
Obsd. (%): C, 67.84, H, 7.12, N, 3.59.
Benzyl-dithiocarbamic acid-2-(naphthalen-2-yloxy)-
ethyl ester (37): Yield: 0.75 g (87.3 %); m.p.: 101 °C; IR (KBr,
ν
max, cm-1): 662 (C-S), 1112 (C=S), 1464 (Ar), 1512 (Ar), 1603
(Ar), 2865 (CH), 2926 (CH), 3385 (NH); 1H NMR (CDCl3): δ
= 2.0 (bs, H, NH), 3.26-3.32 (t, 2H, CH2-S-C=S), 3.92-3.94
(d, 2H, benzylic proton), 4.71-4.73 (t, 2H, CH2-O-naphthyl),
6.98-7.65 (m, 12H, Ar-H of naphthyloxy); Mass: m/e 353;
Analysis: C20H19NOS2, Calcd. (%): C, 67.95, H 5.42, N, 3.96,
Obsd. (%): C, 67.63, H, 5.58, N, 4.12.
Benzyl-dithiocarbamic acid-3-(naphthalen-2-yloxy)-
propyl ester (38): Yield: 0.75 g (89.8 %); m.p.: 109 °C; IR
(KBr, νmax, cm-1): 668 (C-S), 1114 (C=S), 1474 (Ar), 1514
(Ar), 1612 (Ar), 2863 (CH), 2926 (CH), 3398 (NH); 1H NMR
(CDCl3): δ = 2.0 (bs, H, NH), 2.38-2.42 (m, 2H, naphthyl-O-
CH2CH2CH2-S-C=S), 2.82-2.86 (t, 2H, CH2-S-C=S), 3.91-3.93
(d, 2H, CH2 of benzylic hydrogens), 4.01-4.04 (t, 2H, CH2-O-
naphthyl), 6.96-7.62 (m, 12H, Ar-H of naphthyloxy); Mass:
m/e 367;Analysis: C21H21NOS2, Calcd. (%): C, 68.63, H, 5.76,
N, 3.81, Obsd. (%): C, 68.27, H, 5.94, N, 4.02.
Benzyl-dithiocarbamic acid-4-(naphthalen-2-yloxy)-
butyl ester (39): Yield: 0.75 g (92.8 %); m.p.: 119 °C; IR (KBr,
ν
max, cm-1): 673 (C-S), 1126 (C=S), 1484 (Ar), 1529 (Ar), 1612
(Ar), 2873 (CH), 2936 (CH), 3398 (NH); 1H NMR (CDCl3): δ
= 1.71-1.74 (m, 2H, naphthyl-O-CH2CH2), 1.96-1.99 (m, 2H,
S-CH2CH2), 2.0 (bs, H, NH), 2.84-2.88 (t, 2H, CH2-S-C=S),
3.91-3.94 (d, 2H, CH2 of benzylic proton), 4.01-4.04 (t, 2H,
CH2-O-naphthyl), 6.96-7.65 (m, 12H, Ar-H of naphthyloxy);
Mass: m/e 381; Analysis: C22H23NOS2, Calcd. (%): C, 69.25,
H 6.08, N, 3.67, Obsd. (%): C, 69.67, H, 5.87, N, 3.46.
Phenyl ethyl-dithiocarbamic acid-2-(naphthalen-2-
yloxy)ethyl ester (40): Yield: 0.78 g (88.2 %); m.p.: 146 °C;
IR (KBr, νmax, cm-1): 661 (C-S), 1112 (C=S), 1464 (Ar), 1514
(Ar), 1605 (Ar), 2865 (CH), 2923 (CH), 3376 (NH); 1H NMR
(CDCl3): δ = 2.0 (bs, H, NH), 2.80-2.82 (t, 2H, PhCH2), 2.96-
2.98 (m, 2H, NHCH2CH2Ph), 3.28-3.31 (t, 2H, CH2-S-C=S),
4.71-4.73 (t, 2H, CH2-O-naphthyl), 6.98-7.62 (m, 12H, Ar-H
of naphthyloxy and phenyl ring); Mass: m/e 367; Analysis:
C21H21NOS2, Calcd. (%): C, 68.63, H, 5.76, N, 3.81, Obsd.
(%): C, 68.19, H, 6.06, N, 3.95.
Phenyl ethyl-dithiocarbamic acid-3-(naphthalen-2-
yloxy)propyl ester (41): Yield: 0.8 g (91.4 %); m.p.: 172 °C;
IR (KBr, νmax, cm-1): 668 (C-S), 1126 (C=S), 1478 (Ar), 1519
(Ar), 1614 (Ar), 2878 (CH), 2933 (CH), 3396 (NH); 1H NMR
(CDCl3): δ = 2.0 (bs, H, NH), 2.35-2.41 (m, 2H, naphthyl-O-
CH2CH2CH2-S-C=S), 2.80-2.82 (t, 2H, PhCH2), 2.84-2.86 (t,
2H, CH2-S-C=S), 2.96-3.02 (m, 2H, CH2NH), 4.02-4.06 (t,
2H, CH2-O-naphthyl), 6.95-7.62 (m, 12H,Ar-H of naphthyloxy
and phenyl group); Mass: m/e 381; Analysis: C22H23NOS2,
Calcd. (%): C, 69.25, H, 6.08, N, 3.67, Obsd. (%): C, 68.87,
H, 6.29, N, 3.89.
Phenyl ethyl-dithiocarbamic acid-4-(naphthalen-2-
yloxy)butyl ester (42): Yield: 0.8 g (94.8 %); m.p.: 179 °C;
IR (KBr, νmax, cm-1): 679 (C-S), 1149 (C=S), 1487 (Ar), 1533
(Ar), 1622 (Ar), 2884 (CH), 2944 (CH), 3438 (NH); 1H NMR
(CDCl3): δ = 1.72-1.74 (m, 2H, naphthyl-O-CH2CH2), 1.96-
1.97 (m, 2H, S-CH2CH2), 2.01 (bs, H, NH),2.80-2.82 (t, 2H,
PhCH2), 2.86-2.88 (t, 2H, CH2-S-C=S), 2.96-3.00 (m, 2H,
CH2NH), 4.02-4.06 (t, 2H, CH2-O-naphthyl), 6.98-7.62 (m,

Vol. 31, No. 10 (2019)
Synthesis and Antimicrobial Activity of Dithiocarbamates of ω-Substituted (2-naphthyloxy)alkanes 2207
12H, Ar-H of naphthyloxy and phenyl ring); Mass: m/e 395;
Analysis: C23H25NOS2, Calcd. (%): C, 69.93, H, 6.37, N, 3.54,
Obsd. (%): C, 69.57, H, 6.55, N, 3.72.
8.01, N, 3.60, O, 4. 10, S, 16.42. Obsd. (%): C, 67.82, H, 8.02,
N, 3.59, O, 4.11, S, 16.46.
Di-sec-butyl-dithiocarbamic acid-4-(naphthalen-2-
yloxy)butyl ester (48):Yield: 0.84 g (90.2 %); m.p.: 119 °C; IR
(KBr, νmax, cm-1): 668 (C-S), 1114 (C=S), 1465 (Ar), 1514 (Ar),
1600 (Ar), 2865 (CH), 2927 (CH), 3388 (NH); 1H NMR (CDCl3):
δ = 1.08-1.10 (d, CH3), 2.75-2.79 (m, 8H, CH3CH2CH3), 1.38-
1.41 (M, 6H, CH3CHCH3), 0.94-0.96 (t, 2H,CH3CHCH2), 3.27-
3.31 (t, 2H, CH2-S-C=S), 1.92-1.96 (m, 2H, CH2CH2CH2),
1.68-1.71 (m, 2H, CH2CH2CH2), 4.71-4.73 (t, 2H, CH2-O-
naphthyl), 6.97-7.64 (m, 12H,Ar-H of naphthyloxy and phenyl
ring); Mass: m/e 403.64; Analysis: C23H33NOS2, Calcd. (%):
C, 68.41, H 8.20, N, 3.44, O, 3.92, S, 15.87. Obsd. (%): C,
68.44, H, 8.24, N, 3.47, O, 3.96, S, 15.89.
Phenyl propyl-dithiocarbamic acid-2-(naphthalen-2-
yloxy)ethyl ester (43): Yield: 0.84 g (90.2 %); m.p.: 119 °C;
IR (KBr, νmax, cm-1): 668 (C-S), 1114 (C=S), 1462 (Ar), 1514
(Ar), 1600 (Ar), 2862 (CH), 2925 (CH), 3388 (NH); 1H NMR
(CDCl3): δ = 1.86-1.88 (m, 2H, PhCH2CH2CH2NH), 2.0 (bs,
H, NH), 2.54-2.56 (t, 2H, PhCH2), 2.65-2.64 (m, 2H,
NHCH2CH2CH2Ph), 3.28-3.31 (t, 2H, CH2-S-C=S), 4.72-4.74
(t, 2H, CH2-O-naphthyl), 6.95-7.62 (m, 12H, Ar-H of
naphthyloxy and phenyl ring); Mass: m/e 381; Analysis:
C22H23NOS2, Calcd. (%): C, 69.25, H 6.08, N, 3.67, Obsd.
(%): C, 69.66, H, 5.99, N, 3.35.
Phenyl propyl-dithiocarbamic acid-3-(naphthalen-2-
yloxy)propyl ester (44): Yield: 0.84 g (93.2 %); m.p.: 135
°C; IR (KBr, νmax, cm-1): 682 (C-S), 1129 (C=S), 1481 (Ar),
1533 (Ar), 1626 (Ar), 2884 (CH), 2936 (CH), 3416 (NH); 1H
NMR (CDCl3): δ = 1.86-1.89 (m, 2H, Ph.CH2CH2CH2), 2.0
(bs, H, NH), 2.38-2.42 (m, 2H, naphthyl-O-CH2CH2CH2-S-
C=S), 2.52-2.55 (t, 2H, PhCH2), 2.62-2.64 (m, 2H, NHCH2),
2.84-2.88 (t, 2H, CH2-S-C=S), 4.02-4.05 (t, 2H, CH2-O-
naphthyl), 6.98-7.65 (m, 12H,Ar-H of naphthyloxy and phenyl
group); Mass: m/e 395; Analysis: C23H25NOS2, Calcd. (%): C,
69.83, H 6.37, N, 3.54, Obsd. (%): C, 69.34, H, 6.66, N, 3.74.
Phenyl propyl-dithiocarbamic acid-4-(naphthalen-2-
yloxy)butyl ester (45): Yield: 0.85 g (97.6 %); m.p.: 154 °C;
IR (KBr, νmax, cm-1): 692 (C-S), 1139 (C=S), 1486 (Ar), 1539
(Ar), 1628 (Ar), 2882 (CH), 2948 (CH), 3427 (NH); 1H NMR
(CDCl3): δ = 1.71-1.73 (m, 2H, naphthyl-O-CH2CH2), 1.86-
1.88 (m, 2H, PhCH2CH2 CH2NH), 1.96-1.99 (m, 2H, S-
CH2CH2), 2.02 (bs, H, NH), 2.54-2.56 (t, 2H, PhCH2), 2.64-
2.68 (m,2H,PhCH2CH2CH2-N), 2.84-2.86 (t, 2H, CH2-S-C=S),
2.98-3.01 (m, 2H, CH2NH), 4.02-4.06 (t, 2H, CH2-O-
naphthyl), 6.98-7.62 (m, 12H,Ar-H of naphthyloxy and phenyl
ring); Mass: m/e 409; Analysis: C24H27NOS2, Calcd. (%): C,
70.37, H, 6.64, N, 3.42, Obsd. (%): C, 69.95, H, 6.86, N, 3.62.
Di-sec-butyl-dithiocarbamic acid-2-(naphthalen-2-
yloxy)ethyl ester (46): Yield: 0.84 g (90.2 %); m.p.: 119 °C; IR
(KBr, νmax, cm-1): 668 (C-S), 1115 (C=S), 1462 (Ar), 1514 (Ar),
1601 (Ar), 2865 (CH), 2926 (CH), 3388 (NH); 1H NMR (CDCl3):
δ = 1.08-1.10 (d, CH3), 2.75-2.79 (m, 8H, CH3CH2CH3), 1.38-
1.41 (M, 6H, CH3CHCH3), 0.94-0.96 (t, 2H,CH3CHCH2), 3.28-
3.30 (t, 2H, CH2-S-C=S), 4.71-4.73 (t, 2H, CH2-O-naphthyl),
6.95-7.63 (m, 12H, Ar-H of naphthyloxy and phenyl ring);
Mass: m/e 375.59;Analysis: C21H29NOS2, Calcd. (%): C, 67.10,
H 7.75, N, 3.70, O, 4.22, S, 17.05. Obsd. (%): C, 67.15, H,
7.78, N, 3.73, O, 4.26, S, 17.07.
RESULTS AND DISCUSSION
The synthetic route of ω-substituted 2-naphthyloxy halo-
alkanes and desired products (4-48) as shown in Scheme-I is
prepared by direct condensation of β-naphthol and alkyl dihalide.
Intermediate ω-substituted 2-naphthyloxy haloalkanes (3) was
prepared by reacting alkyl dihalide (2) with β-naphthol (1) in
the presence of anhydrous K2CO3 which was subsequently
converted to corresponding dithiocarbamates of 4 to 48 by
reaction of various types of primary and secondary amines
involving Triton B/CS2 system at room temperature. Hence,
dithiocarbamates of desired (4-48) series is synthesized emplo-
ying various kinds of aliphatic, aromatic, alicyclic, heterocyclic
primary and secondary amines. The protocol proved to be
successful and the desired product was isolated and further
confirmed by spectroscopic and analytical methods.
The structural characterization of title compounds have
1
been done by melting point, H NMR, 13C NMR and high-
resolution mass spectrometry (HRMS).All spectral data were
consistent with the assigned structures. The comparative study
of the yield of 3a, 3b and 3c increases with number of carbon
due to +I effect. However, final yield of dithiocarbamates of
Prototype I (4-48) is dependent upon the electron releasing
effect of the amines like pyrrolidine, piperidine, N-methyl
piperazine, cyclohexane, phenyl ethyl amine and phenyl propyl
amine show higher yield compared to primary amines (Table-1).
Antimicrobial screening: The series of compounds were
screened for antimicrobial activity through microdilution
method using various bacterial and fungal strains. The anti-
fungal and antibacteriaal values were estimated as MIC values.
Fluconazole and ciprofloxacin were used as the standard anti-
fungal and antibacterial drug. As shown in Table-2, the SAR
of these compounds can be studied by variying the alkyl chain
and amines attached to these range of compounds. Compounds
having three-carbon chain attached to them are found to be
more active as compared to two-carbon or four-carbon chain.
Among 28, 29, 30 and 31, 32, 33, 29 and 33 were found to
possess higher potency as compared to others because of the
three-carbon chain attached to them. The higher potency of
three-carbon chain is due to hydrophilicity. Upon studying
the effect of various types of amines, we found that compounds
like 28, 29, 30, 31, 32 and 33 having aromatic amine like
anisidine and toludine possessed comparable values to control
drugs. Substitution of heterocyclic amines in compounds 16,
Di-sec-butyl-dithiocarbamic acid-3-(naphthalen-2-
yloxy)propyl ester (47): Yield: 0.84 g (90.2 %); m.p.: 119
°C; IR (KBr, νmax, cm-1): 668 (C-S), 1114 (C=S), 1462 (Ar),
1514 (Ar), 1600 (Ar), 2862 (CH), 2925 (CH), 3388 (NH); 1H
NMR (CDCl3): δ = 1.08-1.10 (d, CH3), 2.75-2.79 (m, 8H,
CH3CH2CH3), 1.38-1.41 (M, 6H, CH3CHCH3), 0.94-0.96 (t,
2H,CH3CHCH2), 3.28-3.30 (t, 2H, CH2-S-C=S), 2.35-2.39(m,
2H, CH2CH2CH2), 4.72-4.74 (t, 2H, CH2-O-naphthyl), 6.96-
7.62 (m, 12H, Ar-H of naphthyloxy and phenyl ring); Mass:
m/e 389.62; Analysis: C22H31NOS2, Calcd. (%): C, 67.80, H

2208 Zaidi et al.
Asian J. Chem.
TABLE-1
SYNTHESIS OF VARIOUS TYPES OF DITHIOCARBAMATES OF ω-SUBSTITUTED 2-NAPHTHYLOXY ALKANES
Comp. No.
n
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
R1
R2
H
H
H
H
H
H
H
H
H
H
H
H
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
Time (min)
35
30
38
30
30
35
40
35
38
40
38
40
25
20
25
30
28
30
20
20
20
25
20
25
25
20
25
30
20
25
25
25
30
40
25
30
20
20
25
25
30
25
30
25
35
Yield (%)
93
95
93
94
95
94
90
94
92
93
95
92
96
98
95
98
95
98
98
98
96
90
92
90
92
94
90
92
90
92
95
92
94
93
96
98
98
98
90
92
92
95
97
95
80
4
5
6
7
8
9
C4H9
C4H9
C4H9
C6H11
C6H11
C6H11
C8H15
C8H15
C8H15
C10H19
C10H19
C10H19
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
R1 = R2 = Pyrrolidine
R1 = R2 = Pyrrolidine
R1 = R2 = Pyrrolidine
R1 = R2 = Piperidine
R1 = R2 = Piperidine
R1 = R2 = Piperidine
R1 = R2 = N-methyl piperazine
R1 = R2 = N-methyl piperazine
R1 = R2 = N-methyl piperazine
R1 = R2 = Morpholine
R1 = R2 = Morpholine
R1 = R2 = Morpholine
R1 = R2 = Toludine
R1 = R2 = Toludine
R1 = R2 = Toludine
R1 = R2 = Anisidine
R1 = R2 = Anisidine
R1 = R2 = Anisidine
R1 = R2 = Cyclohexane
R1 = R2 = Cyclohexane
R1 = R2 = Cyclohexane
Ph(CH2)
H
H
H
H
H
H
H
H
H
–
Ph(CH2)
Ph(CH2)
Ph(CH2CH2)
Ph(CH2CH2)
Ph(CH2CH2)
Ph(CH2CH2CH2)
Ph(CH2CH2CH2)
Ph(CH2CH2CH2)
R1 = R2 = Dibutyl
R1 = R2 = Dibutyl
R1 = R2 = Dibutyl
–
–
17, 18, 19, 20, 21, 22, 23, 24, 25, 26 and 27 gave promising
result. Among substituted aromatic amines benzyl amine (37,
38 and 39) gave better result than phenyl ethyl (40, 41 and 42)
and phenyl propyl amine (43, 44 and 45).
ACKNOWLEDGEMENTS
The authors gratefully acknowledge fruitful discussions
with Dr. Devdutt Chaturvedi and Amity University Uttar
Pradesh (AUUP), Lucknow Campus, Lucknow, U.P., for their
constant encouragement and support for research. Financial
support from the Department of Science and Technology
(DST), Govt. of India (Grant No.SR/FT/CS-147/2010) is grate-
fully acknowledged.
Conclusion
In conclusion, a convenient and efficient protocol for one-
pot synthesis has been developed, employing three components
coupling of various amines with variety of via CS2 Bridge
using Triton-B. This method produces the corresponding dithio-
carbamates in good to excellent yields. Furthermore, the comp-
ounds produces by this method exhibited maximum potency
for antifungal and antibacterial activity which is comparable
to standard drug.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interests
regarding the publication of this article.

Vol. 31, No. 10 (2019)
Synthesis and Antimicrobial Activity of Dithiocarbamates of ω-Substituted (2-naphthyloxy)alkanes 2209
TABLE-2
ANTIMICROBIAL DATA OF DITHIOCARBAMATES OF ω-SUBSTITUTED 2-NAPHTHYLOXY ALKANES
Antifungal activity Antibacterial activity
S. schenckii A. fumigatus
1.52 6.25
Compounds
C. albicans
1.56
1.58
1.60
3.12
3.14
3.18
6.25
6.27
6.30
12.5
12.8
13.0
0.92
0.75
0.82
0.95
0.80
0.88
0.88
0.70
0.80
0.81
0.65
0.74
0.80
0.64
0.72
0.78
0.50
0.65
2.89
2.90
3.28
1.05
0.95
1.10
1.16
1.05
1.22
>50
A. niger
8
S. aureus
6.25
6.27
6.28
8
MRSA*
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
50
E. coli
3.12
3.14
3.18
6.25
6.27
6.28
>50
>50
>50
>50
>50
>50
0.62
0.48
0.54
0.84
0.55
0.72
0.42
0.24
0.36
0.32
0.20
0.25
0.30
0.15
0.19
0.20
0.10
0.15
8
P. aeruginosa
6.25
6.26
6.28
>50
>50
>50
>50
>50
>50
>50
>50
>50
3.12
3.14
3.16
6.25
6.26
6.28
1.38
1.33
1.35
1.25
1.27
1.29
0.72
0.52
0.65
0.68
0.48
0.55
12.5
12.7
13.0
8
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
1.56
1.58
1.56
1.58
1.62
6.25
6.27
6.28
6.25
6.28
6.28
0.32
0.28
0.32
0.35
0.30
0.33
0.30
0.26
0.28
0.29
0.20
0.25
0.25
0.17
0.20
0.20
0.15
0.18
3.12
3.14
3.20
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
0.09
–
6.27
6.28
>50
>50
>50
>50
>50
>50
>50
>50
>50
0.80
0.71
0.78
0.89
0.78
0.85
0.75
0.66
0.70
0.68
0.59
0.62
0.62
0.55
0.58
0.52
0.45
0.50
>50
>50
>50
50
8.5
9
8
8.5
8.8
16
15
18
>50
>50
>50
1.30
1.20
1.25
25
8.8
9
16
17
18
>50
>50
>50
3.12
3.14
3.18
6.25
6.27
6.28
0.78
0.64
0.70
0.76
0.60
0.68
0.68
0.57
0.61
0.59
0.45
0.55
8
24
28
0.82
0.64
0.74
0.66
0.52
0.58
0.58
0.45
0.50
0.50
0.40
0.45
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
0.25
–
50
50
30
24
28
27
20
25
22
18
20
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
–
8.5
9
8.5
9
50
50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
–
50
50
8.8
9
50
>50
>50
>50
>50
>50
>50
>50
>50
>50
0.35
–
>50
>50
>50
>50
>50
>50
>50
>50
>50
–
>50
>50
>50
>50
>50
>50
>50
>50
>50
–
>50
>50
>50
>50
>50
Fluconazone
Ciprofloxacin
0.25
–
0.25
16
0.03
0.25
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